ACTA ZOOLOGICA, Issue 3 2010
Maria Ogielska
Abstract Ogielska, M., Rozenblut, B., Augusty,ska, R., Kotusz, A. 2010. Degeneration of germ line cells in amphibian ovary. ,Acta Zoologica (Stockholm) 91: 319,327 We studied the morphology of degenerating ovarian follicles in juvenile and adult frogs Rana temporaria, Rana lessonae and Rana ridibunda. Degeneration of primordial germ cells was never observed and was extremely rare in oogonia and early oocytes in a cyst phase in juveniles. Previtellogenic oocytes were rarely affected. Three main types of atresia were identified. In type I (subdivided into stages A,D), vitellogenic oocytes are digested by proliferating follicle cells that hypertrophy and become phagocytic. A , germinal vesicle shrinks, nucleoli fuse, oocyte envelope interrupts, and follicular cells hypertrophy; B , follicular cells multiply and invade the oocyte; C , entire vesicle is filled by phagocytic cells; D , degenerating phagocytes accumulate black pigment. Type II is rare and resembles breakdown of follicles and release of ooplasm. In type III, observed in previtellogenic and early vitellogenic oocytes, ooplasm and germinal vesicle shrink, follicle cells do not invade the vesicle, and condensed ooplasm becomes fragmented. The residual oogonia in adult ovaries (germ patches) multiply, but soon degenerate. [source]

The significance of feeding for reproduction in a male Metastriata tick, Haemaphysalis longicornis (Acari: Ixodidae)

ACTA ZOOLOGICA, Issue 1 2000
Tomohide Matsuo
In Haemaphysalis longicornis, secretions of the male accessory genital glands were regenerated by re-feeding for 3 or 4 days, although the secretions were almost completely released during the first copulation. It was also shown that spermatogenesis continued during re-feeding, since prospermia (elongated spermatids) were deposited in the seminal vesicle. A potent male seeks a receptive female on the host for copulation. The movement of males to different attachment sites occurred between the third and fourth day of re-feeding, and completely re-fed males (for 4 days) were able to copulate successfully. Spermatogenic cells, ranging from spermatogonia at the anterior end to prospermia at the posterior end, were found in fed males. Degeneration of spermatocytes at the great growth phase and developing spermatids prior to final development of prospermia were seen in virgin males without re-feeding after the first meal. Fully elongated spermatids (prospermia) appeared morphologically normal up to 10 days after the first feeding. Degeneration of spermatocytes and developing spermatids occurred from the second day and was almost complete by the fourth day. The degenerating cells shrank, became electron-dense, and finally died. A reduction in secretions of the four lobes of the accessory glands occurred during the 10 days after feeding. [source]

Impact of Valvular Calcification on the Diagnostic Accuracy of Transesophageal Echocardiography for the Detection of Congenital Aortic Valve Malformation

ECHOCARDIOGRAPHY, Issue 7 2007
Akash Makkar M.D.
Background: Degeneration of congenital bicuspid or unicuspid aortic valves can progress more rapidly than that of tricuspid valves, and an early diagnosis significantly impacts decision making and outcome. We hypothesized that the extent of valvular calcification would negatively influence the diagnostic accuracy of multiplane transesophageal echocardiography (TEE) for the diagnosis of congenital aortic valve disease. Methods: TEE was performed in 57 patients undergoing aortic valve replacement surgery for aortic stenosis (n = 46), pure regurgitation (n = 9), or significant regurgitation with less than severe aortic stenosis (n = 2). The degree of aortic valve calcification and the number of valve cusps were determined at surgery. Results: Surgical inspection confirmed 14 bicuspid and 43 tricuspid aortic valves. Sensitivity and specificity of TEE for the diagnosis of congenital aortic valve malformation was 93% (13/14) and 91% (39/43) (P = 0.0001), respectively. In patients with no or mild aortic valve calcification (n = 13), sensitivity and specificity of TEE for the diagnosis of congenitally malformed aortic valve was 100% (5/5) and 100% (8/8) (P = 0.001), respectively. In patients with moderate or marked aortic valve calcification (n = 44), sensitivity and specificity of TEE for the diagnosis of congenitally malformed aortic valve was 89% (8/9) and 89% (31/35) (P<0.0001), respectively. In this subgroup of 44 patients, there were four false-positive and one false-negative diagnoses due to valvular calcification. Conclusions: Although TEE is highly sensitive and specific for the detection of congenital aortic valve malformations, presence of moderate or marked calcification of the aortic valve may result in false positive and false negative diagnoses. [source]

Disruption of dopamine homeostasis underlies selective neurodegeneration mediated by ,-synuclein

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2007
Soon S. Park
Abstract A key challenge in Parkinson's disease research is to understand mechanisms underlying selective degeneration of dopaminergic neurons mediated by genetic factors such as ,-synuclein (,-Syn). The present study examined whether dopamine (DA)-dependent oxidative stress underlies ,-Syn-mediated neurodegeneration using Drosophila primary neuronal cultures. Green fluorescent protein (GFP) was used to identify live dopaminergic neurons in primary cultures prepared on a marked photoetched coverslip, which allowed us to repeatedly access preidentified dopaminergic neurons at different time points in a non-invasive manner. This live tracking of GFP-marked dopaminergic neurons revealed age-dependent neurodegeneration mediated by a mutant human ,-Syn (A30P). Degeneration was rescued when ,-Syn neuronal cultures were incubated with 1 mm glutathione from Day 3 after culturing. Furthermore, depletion of cytoplasmic DA by 100 µm,-methyl- p -tyrosine completely rescued the early stage of ,-Syn-mediated dopaminergic cell loss, demonstrating that DA plays a major role in oxidative stress-dependent neurodegeneration mediated by ,-Syn. In contrast, overexpression of a Drosophila tyrosine hydroxylase gene (dTH1) alone caused DA neurodegeneration by enhanced DA synthesis in the cytoplasm. Age-dependent dopaminergic cell loss was comparable in ,-Syn vs dTH1-overexpressed neuronal cultures, indicating that increased DA levels in the cytoplasm is a critical change downstream of mutant ,-Syn function. Finally, overexpression of a Drosophila vesicular monoamine transporter rescued ,-Syn-mediated neurodegeneration through enhanced sequestration of cytoplasmic DA into synaptic vesicles, further indicating that a main cause of selective neurodegeneration is ,-Syn-induced disruption of DA homeostasis. All of these results demonstrate that elevated cytoplasmic DA is a main factor underlying the early stage of ,-Syn-mediated neurodegeneration. [source]

Altered neuronal responses and regulation of neurotrophic proteins in the medial septum following fimbria-fornix transection in CNTF- and leukaemia inhibitory factor-deficient mice

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2006
Thomas Naumann
Abstract Degeneration of axotomized GABAergic septohippocampal neurones has been shown to be enhanced in ciliary neurotrophic factor (CNTF)-deficient mice following fimbria-fornix transection (FFT), indicating a neuroprotective function of endogenous CNTF. Paradoxically, however, the cholinergic population of septohippocampal neurones was more resistant to axotomy in these mutants. As leukaemia inhibitory factor (LIF) has been identified as a potential neuroprotective factor for the cholinergic medial septum (MS) neurones, FFT-induced responses were compared in CNTF,/,, LIF,/, and CNTF/LIF double knockout mice. In CNTF,/, mice, FFT-induced cholinergic degeneration was confirmed to be attenuated as compared with wildtype mice. The expression of both LIF and LIF receptor , was increased in the MS providing a possible explanation for the enhanced neuronal resistance to FFT in these animals. However, ablation of the LIF gene also produced paradoxical effects; following FFT in LIF,/, mice no loss of GABAergic or cholinergic MS neurones was detectable during the first postlesional week, suggesting that other efficient neuroprotective mechanisms are activated in these animals. In fact, enhanced activation of astrocytes, a source of neurotrophic proteins, was indicated by increased up-regulation of glial fibrillary acidic protein and vimentin expression. In addition, mRNA levels for neurotrophin signalling components (e.g. nerve growth factor, p75NTR) were differentially regulated. The positive effect on axotomized cholinergic neurones seen in CNTF,/, and LIF,/, mice as well as the increased up-regulation of astrogliose markers was abolished in CNTF/LIF double knockout animals. Our results indicate that endogenous CNTF and LIF are involved in the regulation of neuronal survival following central nervous system lesion and are integrated into a network of neurotrophic signals that mutually influence their expression and function. [source]

Degeneration of pontine mossy fibres during cerebellar development in weaver mutant mice

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2002
Miwako Ozaki
Abstract In weaver mutant mice, substitution of an amino acid residue in the pore region of GIRK2, a subtype of the G-protein-coupled inwardly rectifying K+ channel, changes the properties of the homomeric channel to produce a lethal depolarized state in cerebellar granule cells and dopaminergic neurons in substantia nigra. Degeneration of these types of neurons causes strong ataxia and Parkinsonian phenomena in the mutant mice, respectively. On the other hand, the mutant gene is also expressed in various other brain regions, in which the mutant may have effects on neuronal survival. Among these regions, we focused on the pontine nuclei, the origin of the pontocerebellar mossy fibres, projecting mainly into the central region of the cerebellar cortex. The results of histological analysis showed that by P9 the number of neurons in the nuclei was reduced in the mutant to about one half and by P18 to one third of those in the wild type, whereas until P7 the number were about the same in wild-type and weaver mutant mice. Three-dimensional reconstruction of the nuclei showed a marked reduction in volume and shape of the mutant nuclei, correlating well with the decrease in neuronal number. In addition, DiI (a lipophilic tracer dye) tracing experiments revealed retraction of pontocerebellar mossy fibres from the cerebellar cortex after P5. From these results, we conclude that projecting neurons in the pontine nuclei, as well as cerebellar granule cells and dopaminergic neurons in substantia nigra, strongly degenerate in weaver mutant mice, resulting in elimination of pontocerebellar mossy fibres during cerebellar development. [source]

Microglial dystrophy in the aged and Alzheimer's disease brain is associated with ferritin immunoreactivity

GLIA, Issue 10 2008
Kryslaine O. Lopes
Abstract Degeneration of microglial cells may be important for understanding the pathogenesis of aging-related neurodegeneration and neurodegenerative diseases. In this study, we analyzed the morphological characteristics of microglial cells in the nondemented and Alzheimer's disease (AD) human brain using ferritin immunohistochemistry. The central hypothesis was that expression of the iron storage protein ferritin increases the susceptibility of microglia to degeneration, particularly in the aged brain since senescent microglia might become less efficient in maintaining iron homeostasis and free iron can promote oxidative damage. In a primary set of 24 subjects (age range 34,97 years) examined, microglial cells immunoreactive for ferritin were found to constitute a subpopulation of the larger microglial pool labeled with an antibody for HLA-DR antigens. The majority of these ferritin-positive microglia exhibited aberrant morphological (dystrophic) changes in the aged and particularly in the AD brain. No spatial correlation was found between ferritin-positive dystrophic microglia and senile plaques in AD tissues. Analysis of a secondary set of human postmortem brain tissues with a wide range of postmortem intervals (PMI, average 10.94 ± 5.69 h) showed that the occurrence of microglial dystrophy was independent of PMI and consequently not a product of tissue autolysis. Collectively, these results suggest that microglial involvement in iron storage and metabolism contributes to their degeneration, possibly through increased exposure of the cells to oxidative stress. We conclude that ferritin immunohistochemistry may be a useful method for detecting degenerating microglia in the human brain. © 2008 Wiley-Liss, Inc. [source]

Age-Related Macular Degeneration: Self-Management and Reduction of Depressive Symptoms in a Randomized, Controlled Study

JOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 10 2006
Barbara L. Brody MPH
OBJECTIVES: To assess the effectiveness of a self-management program for age-related macular degeneration (AMD) in reducing depressive symptoms. DESIGN: Analysis of 6-month follow-up for a subset of participants in a randomized, controlled trial who were clinically depressed at baseline. SETTING: University ophthalmology clinic. PARTICIPANTS: Thirty-two depressed older adult volunteers (mean age 81.5) with advanced AMD who had been randomized to a self-management program (n=12) or one of two control conditions (n=20). Subjects were included if at baseline they met criteria from the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Axis, I, Fourth Edition, Research Version, for major or minor depressive disorder with significant depressive symptoms (,5 points) on the 15-item Geriatric Depression Scale (GDS-15). INTERVENTION: AMD self-management program consisting of cognitive and behavioral elements including health education and enhancement of problem-solving skills. MEASUREMENTS: Primary outcome measure was GDS-15. Secondary outcome measures included National Eye Institute Visual Function Questionnaire (NEI-VFQ) and AMD Self-Efficacy Questionnaire. RESULTS: At 6-month follow-up, the self-management group had a significantly greater reduction in depressive symptoms on the GDS-15 than the controls (P=.03). The mean reduction of 2.92 points in the self-management group was more than the 2-point change threshold considered to be clinically meaningful. Change on the NEI-VFQ was nonsignificant. Reduction in depressive symptoms was associated with greater self-efficacy in the self-management group. CONCLUSION: These findings may support the effectiveness of an AMD self-management program for depressed older adults with advanced vision loss from AMD. [source]

Conduction Characteristics at the Crista Terminalis During Onset of Pulmonary Vein Atrial Fibrillation

JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 8 2004
SIMON P. FYNN M.D.
Introduction: Focal atrial fibrillation (AF) may initiate with an irregular rapid burst of atrial ectopic (AE) activity from a pulmonary vein (PV) focus, but how AF is maintained it is not known. The crista terminalis (CT) is an important line of block in atrial flutter (AFL), but its role in AF has not been determined. The aim of this study was to examine the conduction properties of the CT during onset of AF. Methods and Results: In 10 patients (mean age 38 ± 8 years), we analyzed conduction across the CT during onset of focal AF from an arrhythmogenic PV and during pacing from the same PV at cycle lengths of 700 and 300 ms. A 20-pole catheter was positioned on the CT using intracardiac echocardiography. In 10 control patients with no history of AF, we analyzed conduction across the CT during pacing from the distal coronary sinus at 700 and 300 ms. In all 10 AF patients, AF was initiated with 1 to 9 AE beats (median 5) from a PV. During sinus rhythm, there were no split components (SC) recorded on the CT. During PV AE activity, discrete SC were recorded on the CT in all patients over 6.3 ± 0.9 bipoles (3.7 ± 0.3 cm). Maximal splitting of SC was 66 ± 31 ms (37,139). There was an inverse relationship between AE coupling intervals and the degree of splitting between SC in all patients. Degeneration to AF was preceded by progressive decrement across the CT. SC were recorded during PV pacing at 700 and 300 ms (maximal distance between SC of 24 ± 3 ms and 43 ± 5 ms, respectively, P < 0.001). Maximum SC at CT in controls was 13 ± 8 ms at 700 ms (P = 0.06 vs AF patients) and 16 ± 9 ms at 300 ms (P < 0.01 vs AF patients). Conclusion: (1) These observations provide evidence of anisotropic, decremental conduction across the CT during onset of focal AF and during pacing from the same PV. A line of functional conduction block develops along this anatomic structure (CT). Whether this line of block acts as an initiator of AF or simply contributes passively to nonuniform fibrillatory conduction is unknown. (2) In some patients with focal AF, development of conduction block along the CT may provide a substrate for typical AFL. [source]

Nutritional condition of Anguilla anguilla starved at various salinities during the elver phase

JOURNAL OF FISH BIOLOGY, Issue 2 2005
A. Rodríguez
The effects of food deprivation and environmental salinity (<1, 10 and 20) on survival, fish morphology, organization of the digestive system and body lipid reserves in European eel Anguilla anguilla during the transition from glass eel to elver, were evaluated. Fasted elvers kept in fresh water were able to withstand starvation for >60 days, while those in brackish environments (salinity 10 and 20) reached the level of irreversible starvation at 37 and 35 days, respectively. The high level of lipid reserves contained in liver inclusions and the abdominal cavity (perivisceral deposits) in elvers might explain their long resistance to starvation and differences in fasting tolerance under different salinities. Fasting resulted in a significant reduction of the elvers' condition factor and body depth. There were severe histopathological changes in the digestive system and musculature, such as the alteration of the liver organization, and hepatic glycogen and lipid content, shrinkage of enterocytes and reduction of their height, pancreas degeneration, autolysis of the oesophageal and intestinal mucosa and disarrangement of myofibrils and degeneration of trunk musculature. Degeneration of the oesophageal and intestinal mucosa as a consequence of fasting might have impaired digestive and osmoregulatory functions in feed-deprived fish, directly affecting the tolerance to starvation and survival. Length of food deprivation was associated with a significant increase in mortality, coefficient of variation, cannibalism and point of no return at high salinities. Mortality was dependent on food deprivation and salinity concentrations. Environmental salinity directly influenced the ability of elvers to withstand starvation; once glass eels metamorphosed into elvers, they tolerated starvation better in fresh water than in brackish environments. [source]

Degeneration of Nuclei and Mitochondria in Human Hairs

JOURNAL OF FORENSIC SCIENCES, Issue 2 2009
Charles A. Linch B.S.
Abstract:, It is generally accepted that nuclei degrade in developing hair shafts but the point at which such occurs has not been investigated. The fate of mitochondria in the keratinizing hair shaft has been less clear. This study uses transmission electron microscopy to investigate when nuclei and mitochondria are no longer visible in the developing hair shaft. Serial sections were obtained from anagen head hairs absent follicles in order to determine the sequence of degradation of nuclei and mitochondria in the hair shaft by starting at the root bulb and proceeding toward the hair tip. It was demonstrated that nuclei and mitochondria become invisible in the keratinizing hair shaft at about the same time. This was found to occur fairly early in the process at the level of the hair shaft where the hair cuticle becomes permanent. [source]

Cavernous hemangioma of the liver with giant cyst formation: Degeneration by apoptosis?

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 3 2001
Kazuhiro Hanazaki
Abstract Cavernous hemangioma of the liver with cyst formation is a very rare condition. A case of cavernous hemangioma of the liver with unilocular giant cyst formation undergoing surgical removal is reported. Notably, the patient also had Budd,Chiari syndrome with an obstructing lesion in the inferior vena cava. The cystic degeneration of the hemangioma implied a relationship with apoptosis. This is the first reported case of Budd,Chiari syndrome caused by advanced cystic degeneration of hepatic cavernous hemangioma. [source]

Noradrenergic depletion potentiates ,-amyloid induced cortical inflammation: implications for Alzheimer's disease

JOURNAL OF NEUROCHEMISTRY, Issue 2002
D. L. Feinstein
Degeneration of locus ceruleus (LC) neurons and reduced levels of noradrenaline (NA) in LC projection areas is a well known feature of Alzheimer's disease (AD); however, the consequences of those losses are not clear. Since inflammatory mediators contribute to AD pathogenesis, and since NA can suppress inflammatory gene expression, we tested if LC loss influenced brain inflammatory gene expression elicited by amyloid , (A,). Adult rats were injected with the selective neurotoxin DSP4 to induce LC death, and subsequently injected in cortex with A, (aggregated 1,42 peptide). DSP4-treatment potentiated the A,-dependent induction of inflammatory nitric oxide synthase (iNOS), IL-1, and IL6 expression compared to control animals. In contrast, the induction of cyclooxygenase-2 expression was not modified by DSP4-treatment. In control animals, injection of A, induced iNOS primarily in microglial cells, while in DSP4-treated animals iNOS was localized to neurons, as is observed in AD brains. Injection of A, increased IL-1, expression initially in microglia, and at later times in astrocytes, and expression levels were greater in DSP4 treated animals than controls. The potentiating effects of DSP4-treatment on iNOS and IL-1, expression were attenuated by coinjection with NA or the ,-adrenergic receptor agonist isoproterenol. These data demonstrate that LC loss and NA depletion augment inflammatory responses to A,, and suggest that LC loss in AD is permissive for increased inflammation and neuronal cell death. [source]

Subacute Combined Degeneration Due to Copper Deficiency

JOURNAL OF NEUROIMAGING, Issue 4 2007
Joseph M. Ferrara MD
ABSTRACT There is growing clinical evidence supporting a connection between copper deficiency and subacute combined degeneration. While nearly half of patients with copper deficiency myelopathy exhibit MRI abnormalities, signal changes are often ill-defined in distribution. We report a patient with sensory ataxia and spastic paraplegia from copper deficiency whose MRI demonstrates abnormal signal restricted to the dorsal and lateral columns, providing clear radiological support of an association between hypocupremia and combined system degeneration. [source]

Preferential neurotrophic activity of fibroblast growth factor-20 for dopaminergic neurons through fibroblast growth factor receptor-1c

JOURNAL OF NEUROSCIENCE RESEARCH, Issue 4 2003
Shigeki Ohmachi
Abstract Degeneration of dopaminergic neurons of the substantia nigra causes Parkinson's disease. Therefore, neurotrophic factors for dopaminergic neurons are of substantial clinical interest. Fibroblast growth factor (FGF)-20 preferentially expressed in the substantia nigra pars compacta (SNPC) of the rat brain significantly enhanced the survival of midbrain dopaminergic neurons. Here we examined the mechanism of action of FGF-20 on dopaminergic neurons. FGF-20 slightly enhanced the survival of total neurons of the midbrain, indicating that it preferentially enhanced the survival of dopaminergic neurons. FGF receptor (FGFR)-1c was found to be expressed abundantly in dopaminergic neurons in the SNPC but at much lower levels in neurons of other midbrain regions by in situ hybridization. FGF-20 was also found to bind FGFR-1c with high affinity with the BIAcore system. Furthermore, FGF-20 activated the mitogen-activated protein kinase (MAPK) pathway, which is the major intracellular signaling pathway of FGFs. Both the FGFR-1 inhibitor SU5402 and the MAPK pathway inhibitor PD98059 also significantly inhibited the activation of the MAPK pathway by FGF-20 and the neurotrophic activity of FGF-20. The present findings indicate that the activation of the MAPK pathway by FGF-20 signaling through FGFR-1c plays important roles in the survival of dopaminergic neurons in the SNPC. © 2003 Wiley-Liss, Inc. [source]

Changes of articular cartilage after immobilization in a rat knee contracture model

JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 2 2009
Yoshihiro Hagiwara
Abstract The objective was to determine the changes of articular cartilage of the knee joint during immobilization in a rat model. The knee joints of adult male rats were immobilized at 150° of flexion using an internal fixator for 3 days, and 1, 2, 4, 8, and 16 weeks. The articular cartilage from the medial midcondylar region of the knee was obtained, divided into three areas (non-contact area, transitional area, contact area), and in each area, a degree of degeneration was evaluated by gross observation, histomorphometric grading, and measurements of thickness and number of chondrocytes. Elasticity of the articular cartilage was estimated by measuring the sound speed with use of scanning acoustic microscopy. Degeneration of the articular cartilage was mainly observed in the contact and transitional areas. Matrix staining intensity by safranin-O and number of chondrocytes were decreased in these two areas. The thickness of the articular cartilage in the non-contact and contact areas was unchanged, but it was increased in the transitional area. Decrease in sound speed was observed in the transitional area of both the femoral and tibial cartilage, indicating the softening of the articular cartilage. The changes of articular cartilage became obvious as early as 1 week after immobilization. These changes may be due to a lack of mechanical stress or a lack of joint fluid circulation during immobilization. Although we do not know the reversibility of these changes of articular cartilage, early mobilization is preferable to avoid these cartilage changes. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:236,242, 2009 [source]

Computer-Assisted Magnetic Resonance Imaging Brain Morphometry in American Staffordshire Terriers with Cerebellar Cortical Degeneration

JOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 4 2008
D. Henke
Background: Cerebellar cortical degeneration exists in American Staffordshire Terriers. Magnetic resonance imaging (MRI) can be suggestive, but a definitive diagnosis requires histopathology. Hypothesis: Computer-assisted MRI morphometry can be used to distinguish between American Staffordshire Terriers with or without cerebellar cortical degeneration. Animals: Normal American Staffordshire Terriers (n = 17) and those with clinical signs of cerebellar cortical degeneration (n = 14). Methods: This was a partly retrospective and partly prospective study. Causes of cerebellar disease were ruled out with brain MRI, cerebrospinal fluid (CSF) analysis, CBC, blood biochemistry, and clinical follow-up. On T2-weighted midsagittal MR images, the following parameters were calculated: size of the cerebellum relative to the entire brain, size of the CSF space surrounding the cerebellum relative to the cerebellum, and 2 threshold-dependent cerebellar CSF indices (with and without surrounding CSF). Results: Statistical analyses indicated a significantly lower relative cerebellar size (P < .001) and a larger relative cerebellar CSF space (P < .001) in dogs with cerebellar cortical degeneration. The measurement of relative cerebellar size could distinguish between affected and nonaffected dogs with a sensitivity and a specificity of 93 and 94%, respectively, using a cut-off of 13.3%. Using a cut-off of 12.8%, the measurement of relative CSF space could distinguish between both groups with a sensitivity of 93% and a specificity of 100%. There was a significant difference in 1 of the 2 CSF indices between affected and normal dogs. Conclusions and Clinical Importance: Relative cerebellar size and relative CSF space calculated from MRI are effective in American Staffordshire Terriers to differentiate between normal animals and those with cerebellar cortical degeneration. [source]

Anatomy, physiology, and pathophysiology of the pedunculopontine nucleus,,

MOVEMENT DISORDERS, Issue 3 2009
Ned Jenkinson PhD
Abstract The pedunculopontine nucleus is composed of cholinergic and non-cholinergic neurones and is located in the caudal pontomesencephalic tegmentum. Evidence suggests that the nucleus plays a role in the production and control of movement. The nucleus has dense interconnections with the basal ganglia, as well as with other areas of the brain associated with motor control. Electrical stimulation of the pedunculopontine nucleus in the decerebrate cat or rat produces organized locomotor movements. Physiological studies show that the pedunculopontine nucleus modulates its activity in response to locomotion, as well as voluntary arm and eye movements. Degeneration of the pedunculopontine nucleus is seen in post-mortem brains in humans with Parkinson's disease and Parkinsonian syndromes. In animal models of Parkinson's disease, metabolic changes are seen in the pedunculopontine nucleus, and chemical inhibition or mechanical disruption of the nucleus can produce an akinetic state in animals and man. In this paper we review the literature in support of the suggestion that some of the symptoms of Parkinson's disease are caused by dysfunction of the pedunculopontine nucleus. In accordance with this view, direct stimulation of the nucleus can ameliorate some symptoms of the disease, as demonstrated in both experimental animals and man. © 2008 Movement Disorder Society [source]

Obesity, Lutein Metabolism, and Age-Related Macular Degeneration: A Web of Connections

NUTRITION REVIEWS, Issue 1 2005
Elizabeth J. Johnson PhD
Age-related macular degeneration (AMD) is a major cause of visual impairment in the United States. Currently there is no effective cure for this disease. Risk factors include decreased lutein and zeaxanthin status and obesity. Obesity is also an increasing public health concern. The alarming increase in the prevalence of obesity further exacerbates the public health concern of AMD. The mechanism by which obesity increases the risk of AMD may be related to the physiologic changes that occur with this condition. These include increased oxidative stress, changes in the lipoprotein profile, and increased inflammation. These changes would also result in an increased destruction and a decreased circulatory delivery of lutein and zeaxanthin to the macula of the eye. Therefore, the mechanism by which obesity is related to AMD risk may be through indirect effects on changes in lutein and zeaxanthin status and metabolism. [source]

Lipofuscin and Macular Degeneration

NUTRITION REVIEWS, Issue 10 2003
George Wolf DPhil
The accumulation of the autofluorescent pigment lipofuscin in the retina that occurs with aging has been explained as a side effect of the visual cycle. It occurs when two molecules of all- trans -retinal condense with one molecule of phosphatidylethanolamine in the discs of the rod outer segments, and is followed by uptake into retinal pigment epithelium (RPE) and conversion to the stable A2E, a pyridinium bisretinoid that is toxic to RPE cells. The accumulation of A2E, the major component of lipofuscin causes RPE cell apoptosis, thereby explaining age-related macular degeneration and macular degeneration characteristic of Stargardt disease. The drug isotretinoin (13- cis - retinoic acid) prevents accumulation of A2E in mice by slowing down the visual cycle and might therefore be used to prevent macular degeneration. [source]

Phacomatosis Pigmentokeratotica: A 20-Year Follow-up with Malignant Degeneration of Both Nevus Components

PEDIATRIC DERMATOLOGY, Issue 1 2005
Teresa Martínez-Menchón M.D.
The disorder is a consequence of the so-called twin spot genetic mechanism. We describe the first occurrence involving malignant degeneration of both nevus components, giving rise to three basal cell carcinomas over the sebaceous nevus and a malignant melanoma of the superficial spreading type over the speckled lentiginous nevus. This observation, in concert with the other instances reported in the literature, points to the need for adequate patient follow-up to ensure early detection and treatment of any possible associated malignant degeneration. [source]

Degeneration and regeneration of ultraviolet cone photoreceptors during development in rainbow trout

THE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 5 2006
W. Ted Allison
Abstract Ultraviolet-sensitive (UVS) cones disappear from the retina of salmonid fishes during a metamorphosis that prepares them for deeper/marine waters. UVS cones subsequently reappear in the retina near sexual maturation and the return migration to natal streams. Cellular mechanisms of this UVS cone ontogeny were investigated using electroretinograms, in situ hybridization, and immunohistochemistry against opsins during and after thyroid hormone (TH) treatments of rainbow trout (Oncorhynchus mykiss). Increasing TH levels led to UVS cone degeneration. Labeling demonstrated that UVS cone degeneration occurs via programmed cell death and caspase inhibitors can inhibit this death. After the cessation of TH treatment, UVS cones regenerated in the retina. Bromodeoxyuridine (BrdU) was applied after the termination of TH treatment and was detected in the nuclei of cells expressing UVS opsin. BrdU was found in UVS cones but not other cone types. The most parsimonious explanation for the data is that UVS cones degenerated and UVS cones were regenerated from intrinsic retinal progenitor cells. Regenerating UVS cones were functionally integrated such that they were able to elicit electrical responses from second-order neurons. This is the first report of cones regenerating during natural development. Both the death and regeneration of cones in retinae represent novel mechanisms for tuning visual systems to new visual tasks or environments. J. Comp. Neurol. 499:702,715, 2006. © 2006 Wiley-Liss, Inc. [source]

Analysis of Single Nucleotide Polymorphisms in the NOS2A Gene and Interaction with Smoking in Age-Related Macular Degeneration

ANNALS OF HUMAN GENETICS, Issue 3 2010
Juan A. Ayala-Haedo
Summary Age-related macular degeneration (AMD) is a complex degenerative retinal disease influenced by both genetic and environmental risk factors. We assessed whether single nucleotide polymorphisms (SNPs) in the NOS2A gene increase risk and modulate the effect of smoking in AMD. 998 Caucasian subjects (712 AMD cases and 286 controls) were genotyped for 17 SNPs in NOS2A. Multivariable logistic regression models containing SNP genotypes, age, sex, smoking status and genotype/smoking interaction were constructed. SNP rs8072199 was significantly associated with AMD (OR = 1.3; 95% CI : 1.02, 1.65; P= 0.035). A significant interaction with smoking was detected at rs2248814 (P= 0.037). Stratified data by genotypes demonstrated that the association between AMD and smoking was stronger in carriers of AA genotypes (OR = 35.98; 95% CI: 3.19, 405.98) than in carriers of the AG genotype (OR = 3.05; 95% CI: 1.36, 6.74) or GG genotype (OR = 2.1; 95% CI: 0.91, 4.84). The results suggest a possible synergistic interaction of AA genotype with smoking, although the result bears replication in larger samples. Our data suggests that SNPs in the NOS2A gene are associated with increased risk for AMD and might modulate the effect of smoking on AMD. [source]

Degeneration versus autoimmunity in multiple sclerosis,

ANNALS OF NEUROLOGY, Issue 6 2009
Shigeki Tsutsui
No abstract is available for this article. [source]

Mitochondrial dysfunction as a cause of axonal degeneration in multiple sclerosis patients

ANNALS OF NEUROLOGY, Issue 3 2006
Ranjan Dutta PhD
Objective Degeneration of chronically demyelinated axons is a major cause of irreversible neurological disability in multiple sclerosis (MS) patients. Development of neuroprotective therapies will require elucidation of the molecular mechanisms by which neurons and axons degenerate. Methods We report ultrastructural changes that support Ca2+-mediated destruction of chronically demyelinated axons in MS patients. We compared expression levels of 33,000 characterized genes in postmortem motor cortex from six control and six MS brains matched for age, sex, and postmortem interval. As reduced energy production is a major contributor to Ca2+-mediated axonal degeneration, we focused on changes in oxidative phosphorylation and inhibitory neurotransmission. Results Compared with controls, 488 transcripts were decreased and 67 were increased (p < 0.05, 1.5-fold) in the MS cortex. Twenty-six nuclear-encoded mitochondrial genes and the functional activities of mitochondrial respiratory chain complexes I and III were decreased in the MS motor cortex. Reduced mitochondrial gene expression was specific for neurons. In addition, pre-synaptic and postsynaptic components of GABAergic neurotransmission and the density of inhibitory interneuron processes also were decreased in the MS cortex. Interpretation Our data supports a mechanism whereby reduced ATP production in demyelinated segments of upper motor neuron axons impacts ion homeostasis, induces Ca2+-mediated axonal degeneration, and contributes to progressive neurological disability in MS patients. Ann Neurol 2006 [source]

Why cavefish are blind

BIOESSAYS, Issue 3 2005
Natasha M.M.-L.
Some fish exist as eyed, surface-dwelling and eyeless, cave-dwelling forms. The developmental processes that cause eye degeneration in different populations of Astyanax cavefish are similar. Although small optic primordia start to form, apoptosis of lens cells triggers developmental arrest and degeneration of the eyes. Degeneration has been linked to reduced expression of the transcription factor Pax6 in the anterior embryonic midline and optic primordia. Recently, Yamamoto and colleagues1 reported that increased expression of the diffusible morphogen Sonic hedgehog (Shh) at the embryonic midline of cavefish reduces pax6 expression and increases expression of Shh-regulated genes, which might confer selective advantages for life in caves. BioEssays 27:235,238, 2005. © 2005 Wiley Periodicals, Inc. [source]

Wallerian Degeneration: A Major Component of Early Axonal Pathology in Multiple Sclerosis

BRAIN PATHOLOGY, Issue 5 2010
Tomasz Dziedzic
Abstract Axonal loss is a major component of the pathology of multiple sclerosis (MS) and the morphological basis of permanent clinical disability. It occurs in demyelinating plaques but also in the so-called normal-appearing white matter (NAWM). However, the contribution of Wallerian degeneration to axonal pathology is not known. Here, we analyzed the extent of Wallerian degeneration and axonal pathology in periplaque white matter (PPWM) and lesions in early multiple sclerosis biopsy tissue from 63 MS patients. Wallerian degeneration was visualized using an antibody against the neuropeptide Y receptor Y1 (NPY-Y1R). The number of SMI-32-positive axons with non-phosphorylated neurofilaments was significantly higher in both PPWM and plaques compared to control white matter. APP-positive, acutely damaged axons were found in significantly higher numbers in plaques compared to PPWM. Strikingly, the number of NPY-Y1R-positive axons undergoing Wallerian degeneration was significantly higher in PPWM and plaques than in control WM. NPY-Y1R-positive axons in PPWM were strongly correlated to those in the lesions. Our results show that Wallerian degeneration is a major component of axonal pathology in the periplaque white matter in early MS. It may contribute to radiological changes observed in early MS and most likely plays a major role in the development of disability. [source]

Phosphorylated Map Kinase (ERK1, ERK2) Expression is Associated with Early Tau Deposition in Neurones and Glial Cells, but not with Increased Nuclear DNA Vulnerability and Cell Death, in Alzheimer Disease, Pick's Disease, Progressive Supranuclear Palsy and Corticobasal Degeneration

BRAIN PATHOLOGY, Issue 2 2001
I. Ferrer
Abnormal tau phosphorylation and deposition in neurones and glial cells is one of the major features in tau pathies. The present study examines the involvement of the Ras/MEK/ERK pathway of tau phosphorylation in Alzheimer disease (AD), Pick's disease (PiD), progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD), by Western blotting, single and double-labelling immunohistochemistry, and p21Ras activation assay. Since this pathway is also activated in several paradigms of cell death and cell survival, activated ERK expression is also analysed with double-labelling immunohistochemistry and in situ end-labelling of nuclear DNA fragmentation to visualise activated ERK in cells with increased nuclear DNA vulnerability. The MEK1 antibody recognises one band of 45 kD that identifies phosphorylation-independent MEK1, whose expression levels are not modified in diseased brains. The ERK antibody recognises one band of 42 kD corresponding to the molecular weight of phosphorylation-independent ERK2; the expression levels, as well as the immunoreactivity of ERK in individual cells, is not changed in AD, PiD, PSP and CBD. The antibody MAPK-P distinguishes two bands of 44 kD and 42 kD that detect phosphorylated ERK1 and ERK2. MAPK-P expression levels, as seen with Western blotting, are markedly increased in AD, PiD, PSP and CBD. Moreover, immunohistochemistry discloses granular precipitates in the cytoplasm of neurones in AD, mainly in a subpopulation of neurones exhibiting early tau deposition, whereas neurones with developed neurofibrillary tangles are less commonly immunostained. MAPK-P also decorates neurones with Pick bodies in PiD, early tau deposition in neurones in PSP and CBD, and cortical achromatic neurones in CBD. In addition, strong MAPK-P immunoreactivity is found in large numbers of tau -positive glial cells in PSP and CBD, as seen with double-labelling immunohistochemistry. Yet no co-localisation of enhanced phosphorylated ERK immunoreactivity and nuclear DNA fragmentation is found in AD, PiD, PSP and CBD. Finally, activated Ras expression levels are increased in AD cases when compared with controls. These results demonstrate increased phosphorylated (active) ERK expression in association with early tau deposition in neurones and glial cells in taupathies, and suggest activated Ras as the upstream activator of the MEK/ERK pathway of tau phosphorylation in AD. [source]

1332: Fluorescein angiography: first step for macular degeneration diagnosis

ACTA OPHTHALMOLOGICA, Issue 2010
G SOUBRANE
Purpose To recall that fluorescein angiography (FA) is not only the basis of our knowledge but also mandatory to improve our understanding. Methods Macular disciform lesions have been described and drawed since about 150 years. It is only in 1977 with the advent of fluorescein that the connection with choroidal new vessels (CNV) was performed. The identification of drusen as precursors of CNV was the following stage. With time a number of precursors and clinical forms of macular degeneration were described. Results Currently, the precursors (Age-Related Maculopathy) are distinguished from the neovasdcular or atrophic complications (Age-Related Macular Degeneration). The precursors presenting an early hyperfuorescence can be either hard drusen or RPE atrophy distinguished from each other on the late phase of FA. The late hyperfluorescence of soft drusen particularly when confluent requires a careful analysis of the complete FA sequence to ensure the diagnosis. The neovascular stage presents mainly as sub epithelial occult lesions of which the other types develop that display different angiographic behaviours. Specific aspects have been described gradually based on their FA features. The atrophic stage of the disease seems to behave in a stereotyped way but sub goups are presently identified. Conclusion The fluorescein features of the different component of AMD remain the reference for all other more recent imaging technics and helps to understand and differentiate the various aspects of the disease. [source]

1333: OCT: from single use to combined use in macular degeneration

ACTA OPHTHALMOLOGICA, Issue 2010
C CREUZOT
Purpose Optical Coherence Tomography (OCT) plays a key role in the diagnosis and the treatment of Age Macular Degeneration (AMD). Authors will present the different signs observed in OCT in exudative AMD. Methods Authors will present clinical cases to illustrate the place of the OCT in AMD diagnosis. OCT has progressively replaced the first-line tool played by angiography especially for the following of the patient once the treatment initiated. The different schemas currently proposed emphasize the role of the OCT combined with visual acuity measurement and fundus examination. Results However, the role of fluorescein and indocyanin green angiography remained essential especially to precise the clinical form before treatment. The combination of OCT and angiography remained a "key association" especially when there is some discrepancy between results or in case of treatment failure to consider another option. It is also the only opportunity for us to understand better the prognosis of these cases under treatment. Conclusion OCT has dramatically changed the supervision of exudative AMD especially during treatment. However, the combination with fluorescein and indocyanin angiograms is highly recommended not only for initial diagnosis but also in difficult cases during follow-up. [source]