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Distal Portion (distal + portion)
Selected AbstractsFGF19-FGFR4 signaling elaborates lens induction with the FGF8-L-Maf cascade in the chick embryoDEVELOPMENT GROWTH & DIFFERENTIATION, Issue 4 2005Hitomi Kurose The fibroblast growth factor (FGF) family is known to be involved in vertebrate eye development. However, distinct roles of individual FGF members during eye development remain largely elusive. Here, we show a detailed expression pattern of Fgf19 in chick lens development. Fgf19 expression initiated in the forebrain, and then became restricted to the distal portion of the optic vesicle abutting the future lens placode, where FGF receptor 4 (Fgfr4), a receptor for FGF19, was expressed. Fgf8, a positive regulator for L-Maf, was expressed in a portion of the optic vesicle. To examine the role of FGF19 signaling during early eye development, Fgf19 was misexpressed near the presumptive lens ectoderm; however, no alteration in the expression of lens marker genes was observed. Conversely, a secreted form of FGFR4 was misexpressed to inhibit an FGF19 signal, resulting in the induction of L-Maf expression. To further define the relationship between L-Maf and Fgf19, L-Maf misexpression was performed, resulting in ectopic induction of Fgf19 expression by Hamburger and Hamilton's stage 12/13. Furthermore, misexpression of Fgf8 induced Fgf19 expression in addition to L-Maf. These results suggest that FGF19-FGFR4 signaling plays a role in early lens development in collaboration with FGF8 signaling and L-Maf transcriptional system. [source] Microscopic structure of the sperm storage tubules in the polygynandrous alpine accentor, Prunella collaris (Aves)ACTA ZOOLOGICA, Issue 4 2001Akira Chiba Abstract We describe the microscopic structure of the sperm storage tubules (SSTs) of the polygynandrous alpine accentor, Prunella collaris. The SSTs were found at the utero-vaginal junction of the oviduct and were composed of a single layer of columnar epithelium. The cells of the tubule proper were non-ciliated and had a round or oval nucleus in their basal portion. Their cytoplasm was finely or coarsely vacuolated due to lipid inclusions. Under the electron microscope, the epithelial cells exhibited a number of mitochondria, Golgi bodies, occasional lysosome-like dense bodies, granular endoplasmic reticula, junctional complex, and tonofilaments. The apical margin of the cells was fringed with numerous microvilli. The epithelial lining of the SSTs was devoid of mucous cells, but showed occasional infiltration of lymphoid cells. No contractile elements were found in association with the SSTs, but a close apposition of unmyelinated nerve fibres to the basal part of the SST cells was recognized. Intraluminal sperm were arranged in bundles, and their heads were orientated towards the distal portion of the SSTs. Evidence for engulfment of sperm by the SST cells was obtained for the first time. A sign of atrophy or regression of the SSTs was found in one specimen. [source] Effects of 6° elevation of the heels on 3D kinematics of the distal portion of the forelimb in the walking horseEQUINE VETERINARY JOURNAL, Issue 8 2004H. CHATEAU Summary Reasons for performing study: Understanding of the biomechanical effects of heel elevation remains incomplete because in vivo studies performed with skin markers do not measure the actual movements of the 3 digital joints. Objective: To quantify the effects of 6° heel wedge on the 3-dimensional movements of the 4 distal segments of the forelimb in the walking horse. Methods: Four healthy horses were used. Kinematics of the distal segments was measured invasively with a system based on ultrasonic triangulation. Three-dimensional rotations of the digital joints were calculated by use of a ,joint coordinate system' (JCS). Data obtained with heel wedges were compared to those obtained with standard shoes during the stance phase of the stride. Results: Heel wedges significantly increased maximal flexion of the proximal (PIPJ) and distal (DIPJ) interphalangeal joints and maximal extension (mean ± s.d. +0.8 ± 0.3°) of the metacarpophalangeal joint (MPJ). Extension of the PIPJ and DIPJ was decreased at heel-off. Few effects were observed in extrasagittal planes of movement. Conclusions: Heel wedges affect the sagittal plane kinematics of the 3 digital joints. Potential relevance: Controversial effects previously observed on the MPJ may be explained by the substantial involvement of the PIPJ, which was wrongly neglected in previous studies performed on the moving horse. [source] Association evidence of schizophrenia with distal genomic region of NOTCH4 in Taiwanese familiesGENES, BRAIN AND BEHAVIOR, Issue 6 2007C.-M. Liu Evidence for association with schizophrenia has been reported for NOTCH4, although results have been inconsistent. Previous studies have focused on polymorphisms in the 5, promoter region and first exon of NOTCH4. Our aim was to test the association of the entire genomic region of NOTCH4 in 218 families with at least two siblings affected by schizophrenia in Taiwan. We genotyped seven single nucleotide polymorphisms (SNPs) of this gene, with average intermarker distances of 5.3 kb. Intermarker linkage disequilibrium (LD) was calculated using gold software, and single-locus and haplotype association analyses were performed using transmit software. We found that the T allele of SNP rs2071285 (P= 0.035) and the G allele of SNP rs204993 (P= 0.0097) were significantly preferentially transmitted to the affected individuals in the single-locus association analysis. The two SNPs were in high LD (D, > 0.8). Trend for overtransmission was shown for the T-G haplotype of the two SNPs to affected individuals (P= 0.053), with the A-A haplotype significantly undertransmitted (P= 0.034). The associated region distributed across the distal portion of the NOTCH4 gene and overlapped with the genomic region of the G-protein signaling modulator 3 and pre-B-cell leukemia transcription factor 2. In summary, we found modest association evidence between schizophrenia and the distal genomic region of NOTCH4 in this Taiwanese family sample. Further replication for association with the distal genomic region of NOTCH4 is warranted. [source] DESCRIPTION OF A NEW SPECIES OF THE GENUS CULICOIDES (DIPTERA: CERATOPOGONIDAE) FROM XINGJUNG UYGUR AUT.INSECT SCIENCE, Issue 3 2001Abstract A new species of Culicoides, C. tahemanensis sp. nov. is described from Xingjiang Uygur Aut. Reg. in China. The new species is closely allied to Culicoides grisescens Edwards, but both of them are distinctly different in pale spots of cell R5 and cell A of wing of female, and shape of distal portion of aedeagus of male. The ninth tergum of new species is somewhat allied to C. nipponensis Tokunaga, but distinctly different in pale spots of cell R5, cell M2 and cell A of wing, and shape of aedeagus of male. The type speciemens are deposited in the Institute of Military Medical Sciences, Shenyang Military District, Shengyang 110034, China. [source] Acute febrile neutrophilic dermatosis (Sweet's syndrome) with nodular episcleritis and polyneuropathyINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 2 2002Taizo Kato MD A 56-year-old Japanese housewife presented with multiple erythematous lesions in association with ocular hyperemia and pain in the right upper and lower extremities, including the hands and feet. These symptoms were preceded by a sore throat with persistent fever higher than 38.5 °C for about 1 week. Dermatologic examination showed tender, dull-red, erythematous lesions, measuring 1,2 cm in diameter, located predominantly on the forehead, cheeks, auricular region, neck, forearm, hands, and feet. A biopsy specimen obtained from an erythematous lesion on the right forearm revealed prominent edema in the papillary dermis and remarkable inflammatory cell infiltration throughout the entire dermis (Fig. 1). The infiltrate predominantly consisted of neutrophils and nuclear dust without signs of vasculitis. In routine examination, the leukocyte count was 15,000/mL (normal range, 4000,8000/mL) with severe neutrophilia (80%). The C-reactive protein (CRP) level was 17.65 mg/dL (normal range, < 0.5 mg/dL) and the anti-streptolysin (ASLO) level was 611 IU/mL (normal range, < 166 IU/mL). In human leukocyte antigen (HLA) testing, HLA-A2, -B39, -B35, -Cw2, and -Cw7 were positive, and HLA-B51, -B54, and -Cw1 were negative. Figure Figure 1 . Histologic picture showing a dermal infiltrate of neutrophils Ocular hyperemia was caused by episcleritis forming a nodule and surrounding congestion of the superficial episcleritic vessels at the central portion of the sclera (Fig. 2). The patient suffered from pain once an hour, continuing for about 3 min, at the lateral portion of the right upper and lower extremities, as well as the right small finger. Neurologic examination demonstrated moderate or slight muscle weakness in the extremities. Hand grasping powers were 9 and 7 kg on the right and left, respectively. The patient was right-handed. Dysesthesia and paresthesia were also observed on the hands and feet. The deep tendon reflexes were preserved, however, even in the distal portion of the upper and lower limbs. In addition, essential tremor localized to the neck was recognized. Magnetic resonance imaging did not show any episodes of transient abnormal signal intensity in the central nervous system. Figure 2. Nodular episcleritis (right eye). Telangiectasia of winding vessels with nodular elevation was observed at the upper portion of the sclera The patient was treated with prednisolone (initial dose of 30 mg/day) and intravenous injection of cefazolin sodium (2 g/day for 5 days). Almost complete regression of the ocular and neurologic manifestations, as well as the skin lesions, was achieved in 2 weeks. Prednisolone was reduced gradually and suspended after 4 weeks. Leukocyte and neutrophil counts, CRP, and ASO returned to normal on suspension of therapy. Slight paresthesia remained in the right small finger even after stopping steroid. There was no recurrence at follow-up 6 months later. [source] Reconstructing impairment of secretory ameloblast function in porcine teeth by analysis of morphological alterations in dental enamelJOURNAL OF ANATOMY, Issue 1 2006Carsten Witzel Abstract We studied the relationship between the macroscopic appearance of hypoplastic defects in the dental enamel of wild boar and domestic pigs, and microstructural enamel changes, at both the light and the scanning electron microscopic levels. Deviations from normal enamel microstructure were used to reconstruct the functional and related morphological changes of the secretory ameloblasts caused by the action of stress factors during amelogenesis. The deduced reaction pattern of the secretory ameloblasts can be grouped in a sequence of increasingly severe impairments of cell function. The reactions ranged from a slight enhancement of the periodicity of enamel matrix secretion, over a temporary reduction in the amount of secreted enamel matrix, with reduction of the distal portion of the Tomes' process, to either a temporary or a definite cessation of matrix formation. The results demonstrate that analysis of structural changes in dental enamel allows a detailed reconstruction of the reaction of secretory ameloblasts to stress events, enabling an assessment of duration and intensity of these events. Analysing the deviations from normal enamel microstructure provides a deeper insight into the cellular changes underlying the formation of hypoplastic enamel defects than can be achieved by mere inspection of tooth surface characteristics alone. [source] Myocardial Connections Between Left Atrial Myocardium and Coronary Sinus Musculature in ManJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 9 2001ATSUNOBU KASAI M.D. Connections Between LA Myocardium and CS Musculature.Introduction: Anatomic studies have shown that muscle morphologically identical to that of the atrial myocardium consistently surrounds the coronary sinus (CS). The CS musculature is connected to the left atrial (LA) myocardium in a variable fashion, with fewer connections in its distal portion. The aim of this study was to document the presence of connections between the LA myocardium and the CS musculature, using pacing maneuvers in man, and to study their potential association with natural atrial arrhythmia occurrence. Methods and Results: Thirty patients (19 men; mean age 50.5 years) underwent electrophysiologic study, during which a decapolar catheter with 2-mm interelectrode spacing every 10 mm was inserted into the CS, with the proximal electrode pair positioned at the ostium. Associated atrial arrhythmias were paroxysmal atrial fibrillation in 5, typical atrial flutter in 13, LA flutter in 1, and other in 11. Baseline S1 and a single extrastimulus were delivered during distal and proximal CS pacing, while recordings were obtained from the four remaining bipoles. During distal CS pacing, double potentials with increasing interpotential interval from proximal to distal CS as a function of extrastimulus prematurity were detected in nine patients, suggesting block in a discrete local pathway distally connecting the CS to the LA and leading to reversion of low LA activation. Local delay in this pathway without complete CS-LA block resulting in LA activation fusion was observed in eight patients. A single nonfractionated potential at the distal CS, even at the shortest attainable S1-S2 coupling interval, which was interpreted as no block within distal CS-LA connection(s), was observed in the other 13 patients. History of atrial fibrillation or atypical atrial flutter was found in 8 of 9 patients with block at the distal CS-LA connection but in only 3 of 13 patients with no CS-LA connection block (P = 0.004). Conclusion: The ability to dissociate the LA from the distal CS suggests the presence of discrete connections between these structures in man. This observation appears to be associated with the clinical occurrence of atrial arrhythmias. [source] Dissociation Between Coronary Sinus and Left Atrial Conduction in Patients with Atrial Fibrillation and FlutterJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 6 2001GJIN NDREPEPA M.D. Dissociation Between CS and LA Conduction.Introduction: Coronary sinus (CS) recordings are routinely used during electrophysiologic studies for various supraventricular and ventricular arrhythmias with the understanding that they represent left atrial (LA) activity. However, the behavior of CS electrical activity during atrial arrhythmias has not drawn any special attention beyond standard considerations. Methods and Results: The study population consisted of 9 patients (3 women; mean age 59 ± 11 years) with atrial fibrillation (AF) and atrial flutter (AFL) who developed dissociation of conduction between the CS and posterior LA during spontaneous AF and AFL. In all patients, the LA and the CS were mapped using a 64-electrode basket catheter and a multipolar electrode catheter, respectively. The right atrium (RA) was mapped simultaneously using a 24-polar electrode catheter (7 patients) or a 64-electrode basket catheter (2 patients). Eight patients showed stable double potentials in CS recordings during AF (9 episodes) and AFL (3 episodes). During ongoing arrhythmias, the first row of potentials maintained a constant relationship with the RA activity, whereas the second row of potentials was discordant with the posterior wall of the LA in 7 patients and concordant in 2 patients. In 1 patient with counterclockwise AFL, CS activation was isolated from the posterior wall of the RA until it reached the distal portion of the CS, after which it entered the lateral region of the LA. In 1 patient, a macroreentrant LA tachycardia involving CS muscle was observed. Rapid atrial pacing from the proximal CS and extrastimuli produced longitudinal dissociation of CS activation in all patients. Conclusion: Conduction between the CS and posterior LA can be dissociated during spontaneous atrial arrhythmias and provocative proximal CS pacing. [source] Orthodontic movement in bone defects augmented with Bio-Oss®JOURNAL OF CLINICAL PERIODONTOLOGY, Issue 1 2001An experimental study in dogs Abstract Objective: To study if it was possible to move, by orthodontic means, a tooth into an area of the jaw that had been augmented with Bio-Oss®. Material and Methods: 5 beagle dogs were used. The 1st, 2nd, and 4th mandibular premolars on each side were removed. The defect at the left 4th premolar site was filled with a biomaterial (Bio-Oss®) while the corresponding defect in the right side was left for spontaneous healing. 3 months later, an orthodontic device was inserted in each side of the mandible. The device was designed to allow distal, bodily movement of the 3rd premolars. When the experimental teeth had been moved into the extraction sites of the 4th premolars, the animals were sacrificed and biopsies of the premolar-molar regions of the mandible sampled. The tissues were prepared for histological analysis using standard procedures. In the sections, 3 zones were identified: zone A=the bone tissue within the distal portion of the previous extraction site (4th premolar), zone B=the pressure side of the 3rd premolar, zone C=the tension side of the 3rd premolar. The area occupied by mineralized bone, Bio-Oss® particles and bone marrow was determined by a point counting procedure. The width of the periodontal ligament as well as the percentage of the root surface (in zone B) that exhibited resorption was determined. Results: The findings demonstrated that it was possible to move a tooth into an area of an alveolar ridge that 3 months previously had been augmented with a biomaterial. It was also demonstrated that 12 months after grafting, Bio-Oss® particles remained as inactive filler material in the not utilized part of zone A. The biomaterial was not present in zone C but present in small amounts in zone B. Conclusion: During the orthodontic tooth movement the graft material (Bio-Oss®) was degraded and eliminated from the part of the alveolar ridge that was utilized for the experiment. In the non-utilized part of the ridge the biomaterial, however, remained as a seemingly inactive filler material. [source] Transfemoral Snaring and Stabilization of Pacemaker and Defibrillator Leads to Maintain Vascular Access During Lead ExtractionPACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 3 2009AVI FISCHER M.D. Background: Lead extraction is an effective method for removing pacemaker and defibrillator leads and to obtain venous access when central veins are occluded. Objective: We report a series of patients who required lead extraction and preservation of vascular access requiring a vascular snare introduced from the femoral vein to provide traction on the lead. This technique allowed advancement of the extraction sheath beyond the level of vascular occlusion, preserving vascular access in all patients. Methods: All patients had peripheral contrast venography performed immediately prior to the procedure to identify the site(s) of venous occlusion. An extraction sheath was employed and with direct manual traction, the lead tip pulled free from the myocardial surface prior to advancement of the sheath beyond the occlusion. A transfemoral snare was used to grasp the distal portion of the lead and traction was used to immobilize the lead. Results: In all patients, transfemoral snaring of the leads was necessary to allow safe advancement of a sheath to open the occluded venous system. There were no complications in any of the patients. Conclusion: Our series demonstrates the simple and safe technique of transfemoral lead snaring to assist lead extraction and maintain vascular access in the setting of venous occlusion, when the distal lead tip pulls free of the myocardium before an extraction sheath is passed beyond the point of venous obstruction. [source] Update on the clinical features and natural history of Wolf,Hirschhorn (4p-) syndrome: Experience with 87 patients and recommendations for routine health supervision,AMERICAN JOURNAL OF MEDICAL GENETICS, Issue 4 2008Agatino Battaglia Abstract Wolf,Hirschhorn syndrome (WHS) is a well-known multiple congenital anomalies/mental retardation syndrome, firstly described in 1961 by Cooper and Hirschhorn. Its frequency is estimated as 1/50,000,1/20,000 births, with a female predilection of 2:1. The disorder is caused by partial loss of material from the distal portion of the short arm of chromosome 4 (4p16.3), and is considered a contiguous gene syndrome. No single gene deletions or intragenic mutations have been shown to confer the full WHS phenotype. Since the disorder was brought to the attention of geneticists, many additional cases have been published. Only in 1999, however, were the first data on the natural history brought to the attention of the medical community. The purpose of the present study is to help delineate in more detail and over a longer period of time, the natural history of WHS, in order to establish appropriate health supervision and anticipatory guidance for individuals with this disorder. We have collected information on 87 patients diagnosed with WHS (54 females and 33 males) both in USA and Italy. Age at first observation ranged between newborn and 17 years. Twenty patients have been followed from 4 months to 23 years. The deletion proximal breakpoint varied from 4p15.32 to 4p16.3, and, by FISH, was terminal and included both WHSCR. Deletion was detected by standard cytogenetics in 44/87 (50.5%) patients, whereas FISH was necessary in the other 43 (49.5%). Array-CGH analysis at 1 Mb resolution was performed in 34/87 patients, and, in 15/34 (44%), showed an unbalanced translocation leading to both a 4p monosomy and a partial trisomy for another chromosome arm. Six more patients had been previously shown to have an unbalanced translocation by karyotype analysis or FISH with a WHS-specific probe. Sixty-five of 87 patients had an apparent pure, de novo, terminal deletion; and 1/87 a tandem duplication of 4p16.1p16.3 associated with 4p16.3pter deletion. Age at diagnosis varied between 7 months gestation and 16 years. Ninety-three percent had a seizure disorder with a good outcome; 80% had prenatal onset growth deficiency followed by short stature and slow weight gain; 60% had skeletal anomalies; 50% had heart lesions; 50% had abnormal tooth development; and 40% had hearing loss. Distinctive EEG findings were seen in 90%. Structural CNS anomalies were detected in 80%. Global developmental delay of varying degrees was present in all patients. Almost 50% was able to walk either alone or with support. Hypotonia was present in virtually all patients. A global improvement was observed in all individuals, over time. Our survey has also shown how the characteristic facial phenotype tends to be less pronounced in those patients with a smaller deletion, and microcephaly is not observed in the patients with certain cryptic unbalanced translocations. © 2008 Wiley-Liss, Inc. [source] Crystal structure of the antibiotic albomycin in complex with the outer membrane transporter FhuAPROTEIN SCIENCE, Issue 5 2000Andrew D. Ferguson Abstract One alternative method for drug delivery involves the use of siderophore-antibiotic conjugates. These compounds represent a specific means by which potent antimicrobial agents, covalently linked to iron-chelating siderophores, can be actively transported across the outer membrane of Gram-negative bacteria. These "Trojan Horse" antibiotics may prove useful as an efficient means to combat multi-drug,resistant bacterial infections. Here we present the crystallo-graphic structures of the natural siderophore-antibiotic conjugate albomycin and the siderophore phenylferricrocin, in complex with the active outer membrane transporter FhuA from Escherichia coli. To our knowledge, this represents the first structure of an antibiotic bound to its cognate transporter. Albomycins are broad-host range antibiotics that consist of a hydroxamate-type iron-chelating siderophore, and an antibiotically active, thioribosyl pyrimidine moiety. As observed with other hydroxamate-type siderophores, the three-dimensional structure of albomycin reveals an identical coordination geometry surrounding the ferric iron atom. Unexpectedly, this antibiotic assumes two conformational isomers in the binding site of FhuA, an extended and a compact form. The structural information derived from this study provides novel insights into the diverse array of antibiotic moieties that can be linked to the distal portion of iron-chelating siderophores and offers a structural platform for the rational design of hydroxamate-type siderophore-antibiotic conjugates. [source] Morphological Changes in the Chicken Ductus Arteriosi During Closure at HatchingTHE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 8 2008Candace Belanger Abstract The chicken embryo has two functioning ductus arteriosi (DA) during development. These blood vessels connect the pulmonary arteries to the descending aorta providing a right-to-left shunt of blood away from the nonrespiring lungs and to the systemic circuit and chorioallanotic membrane. The DA consists of two distinct tissue types along its length, a muscular proximal portion and an elastic distal portion. During hatching, the DA must close for proper separation of systemic and pulmonary circulation. We examined the morphological changes of the chicken DA before, during, and after hatching. Occlusion of the proximal DA began during external pipping and was complete at hatching. Anatomical remodeling began as early as external pipping with fragmentation of the internal elastic lamina and smooth muscle actin appearing in the neointimal zone. By day 2 posthatch, the proximal DA lumen was fully occluded by endothelial cells and smooth muscle actin positive cells. In contrast, the distal DA was not fully occluded by day 2 posthatch. Increases in Po2 of the blood serves as the main stimulus for closure of the mammalian DA. The responsiveness of the chicken proximal DA to oxygen increased during hatching, peaking during external pipping. This peak correlated with an increase in blood gas Po2 and the initial occlusion of the vessel. The distal portion remained unresponsive to oxygen throughout hatching. In conclusion, the chicken DA begins to close during external pipping when arterial Po2 increases and vessel tone is most sensitive to oxygen. Anat Rec, 291:1007,1015, 2008. © 2008 Wiley-Liss, Inc. [source] Recombination is suppressed over a large region of the rainbow trout Y chromosomeANIMAL GENETICS, Issue 6 2009R. B. Phillips Summary The previous genetic mapping data have suggested that most of the rainbow trout sex chromosome pair is pseudoautosomal, with very small X-specific and Y-specific regions. We have prepared an updated genetic and cytogenetic map of the male rainbow trout sex linkage group. Selected sex-linked markers spanning the X chromosome of the female genetic map have been mapped cytogenetically in normal males and genetically in crosses between the OSU female clonal line and four different male clonal lines as well as in outcrosses involving outbred OSU and hybrids between the OSU line and the male clonal lines. The cytogenetic maps of the X and Y chromosomes were very similar to the female genetic map for the X chromosome. Five markers on the male maps are genetically very close to the sex determination locus (SEX), but more widely spaced on the female genetic map and on the cytogenetic map, indicating a large region of suppressed recombination on the Y chromosome surrounding the SEX locus. The male map is greatly extended at the telomere. A BAC clone containing the SCAR (sequence characterized amplified region) Omy - 163 marker, which maps close to SEX, was subjected to shotgun sequencing. Two carbonyl reductase genes and a gene homologous to the vertebrate skeletal ryanodine receptor were identified. Carbonyl reductase is a key enzyme involved in production of trout ovarian maturation hormone. This brings the number of type I genes mapped to the sex chromosome to six and has allowed us to identify a region on zebrafish chromosome 10 and medaka chromosome 13 which may be homologous to the distal portion of the long arm of the rainbow trout Y chromosome. [source] Faecal incontinence after lateral internal sphincterotomy is often associated with coexisting occult sphincter defects: A study using endoanal ultrasonographyANZ JOURNAL OF SURGERY, Issue 10 2001Joe J. Tjandra Background: Troublesome faecal incontinence following a lateral internal sphincterotomy (LIS) is often attributed to faulty surgical techniques: division of excessive amount of internal sphincter or inadvertent injury to the external sphincter. The aim of the present paper was to assess the anatomic and physiological factors that may contribute to faecal incontinence following a technically satisfactory lateral internal sphincterotomy by a group of colorectal specialists. Methods: Fourteen patients (nine women, five men; median age: 38 years; range: 23,52 years) who developed troublesome postoperative faecal incontinence were evaluated by clinical assessment, endoanal ultrasonography and anorectal physiological studies (manometry, pudendal nerve terminal motor latency) by two independent observers. The Cleveland Clinic continence score (0,20; 0, perfect continence; 20, complete incontinence) was used to quantify the severity of faecal incontinence. Fourteen continent subjects after a LIS (nine female patients, five male patients; median age: 36 years; range: 20,44 years) were also evaluated as ,continent' controls (continence score , 4). Results: In the incontinent group, the median postoperative Cleveland Clinic continence score was 9 (range: 6,13) compared with a preoperative score of 1 (range: 0,3). On assessment by endoanal ultrasonography the site of the internal sphincterotomy was clearly identified. There were additional coexisting defects, on endoanal ultrasonography, of the external anal sphincter in seven female patients, of the internal sphincter in two female and two male patients; and a defect of both the external and internal sphincters in a male patient who had had a prior fistulotomy. The pudendal nerve terminal motor latency (PNTML) was prolonged in two female patients on the side contralateral to the lateral internal sphincterotomy. In two of five male patients there was no evidence of any occult sphincter injuries. In the continent controls a defect of the distal portion of the external sphincter was noted in one female patient. None of the patients had a prolonged PNTML. The maximum voluntary contraction was significantly lower in the female subjects than in the female continent controls (92 mmHg vs 140 mmHg; P < 0.05), while the resting anal canal pressures and length of the high pressure zone were similar between the study subjects and the continent controls. Conclusion: Troublesome faecal incontinence after a satisfactorily performed lateral internal sphincterotomy is often associated with coexisting occult sphincter defects. [source] Expression of receptor tyrosine kinases epidermal growth factor receptor and HER-2/neu in synovial sarcoma,CANCER, Issue 4 2005Dafydd G. Thomas M.D., Ph.D. Abstract BACKGROUND Synovial sarcomas are high-grade soft tissue neoplasms often characterized by a biphasic spindle and epithelioid cell morphology. The majority of synovial sarcomas harbor a specific chromosomal translocation in which the proximal portion of the SYT gene at chromosome 18q11 is fused to the distal portion of one of several duplicated SSX genes (most notably SSX1 and SSX2) at chromosome Xp11. SYT/SSX1 translocations are seen in nearly three times as many synovial sarcomas as SYT/SSX2 translocations. Although the SYT/SSX2 fusion is usually associated with the monophasic disease pattern, the SYT/SSX1 fusion is present in tumors with biphasic or monophasic patterns. The SYT/SSX1 fusion gene is associated with more aggressive tumor growth and poor outcome. Despite advances in the therapy of local disease, distant metastasis remains the predominant cause of death. Accordingly, there is a need for alternate therapies, such as those recently developed against the receptor tyrosine kinases, such as epidermal growth factor receptor (EGFR) and HER-2/neu. METHODS Archival specimens of synovial sarcoma (n = 38) representing 30 patients were assessed for EGFR and HER-2/neu protein expression by standard immunohistochemical techniques. To validate the immunohistochemistry results, quantitative real-time polymerase chain reaction (Q-PCR) assays using either fresh and/or archival material was performed. The presence of gene amplification was determined by chromogenic in-situ hybridization. RESULTS EGFR and HER-2/neu protein were detected by immunohistochemistry in 21 of 38 (55.3%) and 20 of 38 (52.6%) synovial specimens, respectively. EGFR immunoreactivity showed a granular and membranous pattern, whereas HER-2/neu immunoreactivity demonstrated only a membrane pattern. Coexpression was observed in 13 of 38 specimens (34.2%). HER-2/neu expression by immunohistochemistry in synovial sarcomas was restricted to tumors with the SYT/SSX1 translocations. Of 6 specimens with SSX2 translocation, none (0%) showed HER-2/neu immunoreactivity and 1 (17%) demonstrated EGFR expression. Q-PCR demonstrated the presence of mRNA for EGFR and HER-2/neu in 19 of 30 specimens (63.3%) and 22 of 30 specimens (73.3%), respectively. EGFR and HER-2/neu were expressed at low concentrations compared with the expression of glyceraldehyde 3-phosphate dehydrogenase (GAPDH). No evidence of gene amplification was observed. CONCLUSIONS EGFR and HER-2/neu are expressed in the majority of patients with SYT/SSX1 synovial sarcomas, albeit at low levels. Treatment with tyrosine kinase inhibitors may represent appropriate alternate therapy for these patients. Cancer 2005. © 2005 American Cancer Society. [source] Initial stages of neural regeneration in Helisoma trivolvis are dependent upon PLA2 activityDEVELOPMENTAL NEUROBIOLOGY, Issue 4 2003Matthew S. Geddis Abstract Neuronal regeneration after damage to an axon tract requires the rapid sealing of the injured plasma membrane and the subsequent formation of growth cones that can lead regenerating processes to their appropriate target. Membrane sealing and growth cone formation are Ca2+ -dependent processes, but the signaling pathways activated by Ca2+ to bring about these effects remain poorly understood. An in vitro injury model was employed in which neurites from identified snail neurons (Helisoma trivolvis) were transected with a glass microknife, and the formation of new growth cones from the distal portions of transected neurites was recorded at defined times after transection. This study presents three main results. First, phospholipase A2 (PLA2), a calcium-activated enzyme, is necessary for membrane sealing in vitro. Second, PLA2 activity is also required for the formation of a new growth cone after the membrane has sealed successfully. Thus, PLA2 plays a dual role by affecting both growth cone formation and membrane sealing. Third, the injury-induced activation of PLA2 by Ca2+ controls growth cone formation through the production of leukotrienes, secondary metabolites of PLA2 activity. Taken together, these results suggest that the injury-induced Ca2+ influx acts via PLA2 and leukotriene production to assure growth cone formation. These findings indicate that events that cause an inhibition of PLA2 or lipoxygenases, enzymes that produce leukotrienes, could result in the inability of neurites to regenerate. © 2003 Wiley Periodicals, Inc. J Neurobiol 54: 555,565, 2003 [source] Fibromuscular dysplasia of cervical and intracranial arteriesINTERNATIONAL JOURNAL OF STROKE, Issue 4 2010Emmanuel Touzé Fibromuscular dysplasia is an uncommon, segmental, nonatherosclerotic arterial disease of unknown aetiology. The disease primarily affects women and involves intermediate-sized arteries in many areas of the body, including cervical and intracranial arteries. Although often asymptomatic, fibromuscular dysplasia can also be associated with spontaneous dissection, severe stenosis that compromises the distal circulation, or intracranial aneurysm, and is therefore responsible for cerebral ischaemia or subarachnoid haemorrhage. Fibromuscular dysplasia affects middle and distal portions of the internal carotid and vertebral arteries, and occasionally, intracranial arteries. Several pathological and angiographic patterns exist. The most frequent pathological type is medial fibromuscular dysplasia, which is associated with the ,string of beads' angiographic pattern. Unifocal lesions are less common and can be associated with several pathological subtypes. The pathophysiology of the disease is widely unknown. Fibromuscular dysplasia may in fact result from various causes and reflect a non-specific response to different insults. The poor knowledge of the natural history and the lack of randomised trials that compared the different treatment options do not allow any satisfactory judgement to be made regarding the need for or the efficacy of any treatment. [source] Maternal and fetal microvasculature in sheep placenta at several stages of gestationJOURNAL OF ANATOMY, Issue 3 2010Shireen A. Hafez Abstract Maternal and fetal microvasculature was studied in ewes at days 50, 90 and 130 of gestation using microvascular corrosion casting and scanning electron microscopy. Microvascular corrosion casts of caruncles at day 50 were cup-shaped with a centrally located cavity. Branches of radial arteries entered the caruncle from its base and ramified on the maternal surface of the caruncle. Stem arteries broke into an extensive mesh of capillaries forming crypts on the fetal surface. The architecture of the caruncle at day 90 was similar to what was found at day 50 but the vascularity and the depth of the crypts increased in correspondence to increased branching of fetal villi. The substance of the caruncle was thicker at day 130 compared with day 50, with no remarkable difference compared with day 90. Capillary sinusoids of irregular form and diameter were observed on the fetal surface of the caruncle at all stages. These sinusoids may reduce blood flow resistance and subsequently increase transplacental exchange capacity. A microvascular corrosion cast of the cotyledon was cup-shaped with wide and narrow sides. Cotyledonary vessels entered and left the cotyledon from the narrow side. A cotyledonary artery gave proximal collateral branches immediately after entering the cotyledon and then further branched to supply the remaining portion of the cotyledon. Vessel branches broke into a mesh of capillaries forming the fetal vascular villi. Fetal villi that were nearest to the center of the cotyledon were the longest. Capillaries forming villi were in the form of a web-like mesh, were irregular in size and had sinusoidal dilations. The architecture of the cotyledon at day 90 was similar to day 50, but the vascularity increased. Branching of the fetal villi became more abundant. This extensive branching presumably allows a higher degree of invasion and surface contact to maternal tissues. At day 130, the distal portions of the fetal villi showed low ridges and troughs to increase the surface area for diffusion. Branching of fetal villi appears to influence the elaboration of maternal crypts in all stages of gestation. However, correspondence between crypts and villi is restricted to distal portions of fetal villi. [source] The microanatomy of the distal arrector pili: possible role for ,1,1 and ,5,1 integrins in mediating cell-cell adhesion and anchorage to the extracellular matrixJOURNAL OF CUTANEOUS PATHOLOGY, Issue 2 2000Jeri Kersten Mendelson The arrector pili (AP) muscle is a small band of smooth muscle that attaches proximally to the bulge area of the pilosebaceous apparatus in the reticular dermis and extends up toward the epidermis. The distal anatomy of the AP and the anchorage mechanism allowing hair erection have not been previously described. Integrins are likely candidates mediating this attachment. Immunohistochemical techniques were used to determine the distribution of the following integrins: ,1, ,2, ,3, ,4, ,5, ,6 and ,1 as well as fibronectin. Frozen human scalp tissue was sectioned in traditional planes, obliquely and horizontally to visualize microanatomy in three dimensions. Histological examination revealed that the distal portions of smooth muscle fibers splay extensively between collagen bundles of the upper dermis. Integrin subunits ,1, ,5 and ,1 were expressed by the AP muscle. Analysis of the relative density of immunoreactivity in digitized sections revealed increased ,5 subunit expression at the extracellular matrix (ECM)-muscle interface. These data suggest that anchorage of the AP muscle to the ECM is via ,5,1 integrin and ,1,1 integrin functions in muscle cell-cell adhesion. Extensive splaying of smooth muscle fibers may allow increased surface area contact between the ECM and smooth muscle cells expressing peripherally situated ,5 integrin. [source] Improvement in site-specific intestinal absorption of furosemide by Eudragit L100-55JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 4 2001T. Terao Furosemide (frusemide) is a weakly acidic diuretic drug. Its absorption is poor and variable, in part due to its restricted sites of absorption, mainly the stomach. The narrow absorption window of this drug can be explained by pH partition theory. The purpose of this study was to investigate the feasibility of widening the absorption window of furosemide by controlling the pH in distal portions of the gastrointestinal tract with officially used additives. Methacrylate copolymer (Eudragit L100,55), hydroxypropylmethylcellulose phthalate (HP-55) and hydroxypropylmethylcellulose acetate succinate (AS-MF) were selected as additives. The pH of suspensions of these additives was about 4, and the pH was adjusted to about 6,7 by the addition of NaOH. The Eudragit L100,55 suspension was found to be the most resistant to NaOH titration. When Eudragit L100,55 was used in an in-situ ileal loop experiment in rats, the pH of the intestinal contents was significantly reduced, from 7.9 ± 0.1 to 5.7 ± 0.1, and the plasma concentration of furosemide 15 min after administration was about 3 times higher than that in controls, 1.81 ± 0.42 ,g mL,1 vs 0.63 ± 0.08 ,g mL,1. However, the plasma concentration of [14C] mannitol was not changed by the co-administration of Eudragit L100,55. Furthermore, the AUC of furosemide was significantly increased by a factor of about 1.6 relative to that in controls by the co-administration of Eudragit L100,55, to 21.4 ± 4.0 ,g h mL,1 from 13.3 ± 3.9 ,g h mL,1, and the gastrointestinal pH in the midgut and ileum was significantly reduced, with most of the furosemide remaining in these segments at 2 h following the oral administration of furosemide with Eudragit L100,55 to rats. These findings clearly demonstrate that the addition of Eudragit L100,55 can increase the absorption of furosemide in distal portions of the gastrointestinal tract. In conclusion, it is feasible to widen the absorption window of furosemide by controlling the pH in distal portions of the gastrointestinal tract by the co-administration of Eudragit L100,55. [source] Clinical electrophysiological characterization of the acquired neuromyotonia phenotype of autoimmune peripheral nerve hyperexcitabilityMUSCLE AND NERVE, Issue 6 2006Paul Maddison MD Abstract Acquired autoimmune neuromyotonia is regarded as part of the spectrum of peripheral nerve hyperexcitability disorders. We aimed to use clinical neurophysiological measurements to study the extent, distribution, and characteristics of spontaneous motor unit potentials in 11 patients with acquired neuromyotonia. Investigations revealed that most spontaneous discharges recorded were motor unit, or partial motor unit potentials of normal size. Bursts of motor unit potentials arose more commonly from distal portions of the peripheral nerve and had abnormal absolute and relative refractory periods. Spontaneous discharges in some patients occurred in semirhythmic bursts in certain muscles. No patient had neurophysiological abnormalities detectable in first-order neurons of the central nervous system when using transcranial magnetic stimulation to estimate the threshold for corticomotor excitation and determine central motor conduction time. Only patients with coexistent myasthenia gravis had neurophysiologically detectable defects in neuromuscular transmission. The pathogenic region of abnormality in peripheral nerve hyperexcitability disorders therefore seems to lie within the terminal branches of peripheral motor nerves. Muscle Nerve, 2006 [source] Successful treatment of a 9-year-old boy affected by acrodermatitis continua of Hallopeau with targeted ultraviolet B narrow-band phototherapyPHOTODERMATOLOGY, PHOTOIMMUNOLOGY & PHOTOMEDICINE, Issue 1 2010Matteo Bordignon Acrodermatitis continua of Hallopeau (ACH) consists of a relapsing pustular eruption of the distal portions of hands and feet. We described a case of a 9-year-old boy affected by ACH, successfully treated with targeted ultraviolet B 311 nm phototherapy, which seems to be an effective and safe therapy for this condition. [source] Haplotypes of the Human RET Proto-oncogene Associated with Hirschsprung Disease in the Italian Population Derive from a Single Ancestral Combination of AllelesANNALS OF HUMAN GENETICS, Issue 1 2006F. Lantieri Summary The RET proto-oncogene is the major gene involved in the complex genetics of Hirschsprung disease (HSCR), or aganglionic megacolon, showing causative loss-of-function mutations in 15,30% of the sporadic cases. Several RET polymorphisms and haplotypes have been described in association with the disease, suggesting a role for this gene in HSCR predisposition, also in the absence of mutations in the coding region. Finally, the presence of a functional variant in intron 1 has repeatedly been proposed to explain such findings. Here we report a case-control study conducted on 97 Italian HSCR sporadic patients and 85 population matched controls, using 13 RET polymorphisms distributed throughout the gene, from the basal promoter to the 3,UTR. Linkage disequilibrium and haplotype analyses have shown increased recombination between the 5, and 3, portions of the gene and an over-representation, in the cases studied, of two haplotypes sharing a common allelic combination that extends from the promoter up to intron 5. We propose that these two disease-associated haplotypes derive from a single founding locus, extending up to intron 19 and successively rearranged in correspondence with a high recombination rate region located between the proximal and distal portions of the gene. Our results suggests the possibility that a common HSCR predisposing variant, in linkage disequilibrium with such haplotypes, is located further downstream than the previously suggested interval encompassing intron 1. [source] Retinal and Optic Nerve DiseasesARTIFICIAL ORGANS, Issue 11 2003Eyal Margalit Abstract:, A variety of disease processes can affect the retina and/or the optic nerve, including vascular or ischemic disease, inflammatory or infectious disease, and degenerative disease. These disease processes may selectively damage certain parts of the retina or optic nerve, and the specific areas that are damaged may have implications for the design of potential therapeutic visual prosthetic devices. Outer retinal diseases include age-related macular degeneration, pathologic myopia, and retinitis pigmentosa. Although the retinal photoreceptors may be lost, the inner retina is relatively well-preserved in these diseases and may be a target for retinal prosthetic devices. Inner retinal diseases include retinal vascular diseases such as diabetic retinopathy, retinal venous occlusive disease, and retinopathy of prematurity. Other retinal diseases such as ocular infections (retinitis, endophthalmitis) may affect all retinal layers. Because the inner retinal cells, including the retinal ganglion cells, may be destroyed in these diseases (inner retinal or whole retinal), prosthetic devices that stimulate the inner retina may not be effective. Common optic nerve diseases include glaucoma, optic neuritis, and ischemic optic neuropathy. Because the ganglion cell nerve fibers themselves are damaged, visual prosthetics for these diseases will need to target more distal portions of the visual pathway, such as the visual cortex. Clearly, a sound understanding of retinal and optic nerve disease pathophysiology is critical for designing and choosing the optimal visual prosthetic device. [source] | |||||||||||||||||||||||||