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S S Chin

Publications and source records attributed to S S Chin.

At least 19 recordsLinked to original sources
PubMed2004

Reversible leukoencephalopathy associated with cerebral amyloid angiopathy.

The authors describe three patients with reversible leukoencephalopathy associated with cerebral amyloid angiopathy (CAA). Rapid progression of neurologic symptoms was followed by dramatic clinical and radiographic improvement. Pathologically, CAA was associated with varying degrees of inflammation ranging from none to transmural granulomatous infiltration. In the appropriate clinical context, the MRI finding of lobar white matter edema with evidence of prior hemosiderin deposition may indicate the presence of a reversible CAA leukoencephalopathy.

Aged↗
PubMed2002

Office of Rare Diseases neuropathologic criteria for corticobasal degeneration.

A working group supported by the Office of Rare Diseases of the National Institutes of Health formulated neuropathologic criteria for corticobasal degeneration (CBD) that were subsequently validated by an independent group of neuropathologists. The criteria do not require a specific clinical phenotype, since CBD can have diverse clinical presentations, such as progressive asymmetrical rigidity and apraxia, progressive aphasia, or frontal lobe dementia. Cortical atrophy, ballooned neurons, and degeneration of the substantia nigra have been emphasized in previous descriptions and are present in CBD, but the present criteria emphasize tau-immunoreactive lesions in neurons, glia, and cell processes in the neuropathologic diagnosis of CBD. The minimal pathologic features for CBD are cortical and striatal tau-positive neuronal and glial lesions, especially astrocytic plaques and thread-like lesions in both white matter and gray matter, along with neuronal loss in focal cortical regions and in the substantia nigra. The methods required to make this diagnosis include histologic stains to assess neuronal loss, spongiosis and ballooned neurons, and a method to detect tau-positive neuronal and glial lesions. Use of either the Gallyas silver staining method or immunostains with sensitive tau antibodies is acceptable. In cases where ballooned neurons are sparse or difficult to detect, immunostaining for phospho-neurofilament or alpha-B-crystallin may prove helpful. Methods to assess Alzheimer-type pathology and Lewy body pathology are necessary to rule out other causes of dementia and Parkinsonism. Using these criteria provides good differentiation of CBD from other tauopathies, except frontotemporal dementia and Parkinsonism linked to chromosome 17, where additional clinical or molecular genetic information is required to make an accurate diagnosis.

Atrophy↗
PubMed2001

Cortical basal ganglionic degeneration.

In this case study, we describe the symptoms, neuropsychological testing, and brain pathology of a retired mason's assistant with cortical basal ganglionic degeneration (CBGD). CBGD is an extremely rare neurodegenerative disease that is categorized under both Parkinsonian syndromes and frontal lobe dementias. It affects men and women nearly equally, and the age of onset is usually in the sixth decade of life. CBGD is characterized by Parkinson's-like motor symptoms and by deficits of movement and cognition, indicating focal brain pathology. Neuronal cell loss is ultimately responsible for the neurological symptoms.

Aged↗
PubMed2001

Alzheimer's disease.

In this case study, we describe the symptoms, neuropsychological testing, and brain pathology of a man with Alzheimer's disease (AD). AD commonly presents with impairment of memory and language function. In this case, language difficulties were noted more prominently than was memory impairment. Throughout the limbic system and neocortex of the patient were large numbers of senile plaques and neurofibrillary tangles, the pathological hallmarks of AD.

Aged↗
PubMed2000

Amyotrophy in prion diseases.

Amyotrophic lateral sclerosis was once thought to be caused by persistent viral infection, partly because some patients with transmissible Creutzfeldt-Jakob disease showed prominent amyotrophy. However, in the past 15 years there has been little interest in the amyotrophy in prion diseases, and the possible link to amyotrophic lateral sclerosis has been eschewed. We analyzed case reports of prion disease published after 1968 for evidence of amyotrophy. We defined amyotrophy as clinically evident fasciculation buttressed by electromyographic results in some cases. We sought evidence of motor neuron degeneration at autopsy. Prion disease was proved by transmissibility, immunohistochemistry demonstration of protease-resistant prion protein, or finding a mutation in the prion protein gene. Amyotrophy was noted in 27 patients: 13 with sporadic Creutzfeldt-Jakob disease, 2 with familial Creutzfeldt-Jakob disease, and 12 with Gerstmann-Sträussler-Scheinker disease. Of the 27, 23 showed clinical fasciculation and 10 had electromyographic evidence of denervation. The spinal cord was examined in 8 patients: 6 showed loss of motor neurons, 1 showed vacuolation of motor neurons, and 1 reported no abnormalities. Another 23 patients had typical histopathological characteristics but lacked molecular or biochemical proof of prion disease. The total number of patients with amyotrophy and proven prion disease that we identified was 50. This case review supports the belief that amyotrophy is occasionally a prominent feature of Creutzfeldt-Jakob disease and underscores the importance of documenting lower motor neuron function and the crucial role of examining the spinal cord at autopsy in cases of prion disease.

Amyotrophic Lateral Sclerosis↗
PubMed1999

Characterization of NF-L and betaIISigma1-spectrin interaction in live cells.

Neurofilaments (NFs) are neuron-specific intermediate filaments (IFs) composed of three different subunits, NF-L, NF-M, and NF-H. NFs move down the axon with the slow component of axonal transport, together with microtubules, microfilaments, and alphaII/betaII-spectrin (nonerythroid spectrin or fodrin). It has been shown that alphaII/betaII-spectrin is closely associated with NFs in vivo and that betaII-spectrin subunit binds to NF-L filaments in vitro. In the present study we seek to elucidate the relationship between NF-L and betaII-spectrin in vivo. We transiently transfected full-length NF-L and carboxyl-terminal deleted NF-L mutants in SW13 Cl.2 Vim- cells, which lack an endogenous IF network and express alphaII/betaIISigma1-spectrin. Double-immunofluorescence and electron microscopy studies showed that a large portion of betaIISigma1-spectrin colocalizes with the structures formed by NF-L proteins. We found a similar association between NF-L proteins and actin. However, coimmunoprecipitation experiments in transfected cells and the yeast two-hybrid system results failed to demonstrate a direct interaction of NF-L with betaIISigma1-spectrin in vivo. The presence of another protein that acts as a bridge between the membrane skeleton and neurofilaments or modulating their association may therefore be required.

Animals↗
PubMed1999

A clinicopathological comparison of community-based and clinic-based cohorts of patients with dementia.

OBJECTIVES: To compare the sensitivity and specificity of the clinical diagnosis of Alzheimer disease, the distribution of pathological causes, and the demographic and clinical characteristics of 2 different groups of patients with dementia. DESIGN: Retrospective clinicopathological study. SETTING: A memory disorder clinic in a university hospital and a multiethnic community. PATIENTS: Sixty-three patients from a memory disorder clinic and 26 patients from a large community-based study who underwent autopsy after clinical evaluation. MAIN OUTCOME MEASURES: Differential distribution of clinical and pathological findings, with clinicopathological correlations. RESULTS: Clinic patients were younger at diagnosis, more educated, and more likely to be white. Of the 63 clinic patients we evaluated, 29 (46%) had a pathological diagnosis of definite AD, 15 (24%) had a diagnosis of mixed AD, and 19 (30%) had a diagnosis of another type of dementia. The pathological diagnoses in the community patients were distributed as follows: 6 (23%) had definite AD, 6 (23%) had mixed AD, 6 (23%) had cerebrovascular disease, and 8 (31%) had another type of dementia. The difference in distribution of pathological diagnoses between these 2 groups was only significant for cerebrovascular diseases. For patients seen at the clinic, the sensitivity of the clinical diagnosis of AD was 98% and the specificity was 84%; for the community group, the sensitivity was 92% and the specificity was 79%. CONCLUSIONS: The difference in sensitivity and specificity of clinical diagnosis was not statistically significant between the groups of clinic patients and community patients. Dementia associated with cerebrovascular disease was more prevalent in the community sample. This difference may be attributable to clinical and demographic differences between the 2 groups.

Age Factors↗
PubMed1999

Mother with amyotrophic lateral sclerosis and daughter with Creutzfeldt-Jakob disease.

OBJECTIVE: To describe a mother who had autopsy-proved amyotrophic lateral sclerosis and her daughter who had clinically diagnosed Creutzfeldt-Jakob disease. DESIGN: Case reports with molecular genetic analyses. SETTING: A tertiary care center. PATIENTS: The mother had progressive upper and lower motor neuron symptoms and signs starting at the age of 54 years. Electrophysiological testing supported the diagnosis of amyotrophic lateral sclerosis. Autopsy results confirmed the diagnosis. Her daughter had received injections of human growth hormone prepared from pooled human pituitary glands as a child. At the age of 31 years, she experienced the onset of gait ataxia and dysarthria. Cerebrospinal fluid showed the 14-3-3 protein. Cognitive difficulties ensued. She progressed to a nearly akinetic and mute state. She had overt visible fasciculations and muscle atrophy in the legs. MAIN OUTCOME MEASURES AND RESULTS: Neither patient carried a mutation in the prion protein gene. Both were homozygous for methionine at the polymorphic codon 129. Neither patient carried a deletion of the 5 exons of the superoxide dismutase 1 gene. CONCLUSIONS: It is uncertain whether the 2 cases occurred in the same family by chance or whether the patients shared genetic risk factors for the 2 diseases. The possibility that homozygosity at codon 129 is a risk factor for amyotrophic lateral sclerosis is being tested in a case-control study.

Adult↗
PubMed1999

The natural history of CADASIL: a pooled analysis of previously published cases.

BACKGROUND AND PURPOSE: Although numerous families with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) have been reported, our understanding of the disease remains incomplete. Thus, we performed this study to investigate the phenotypic range and natural history of CADASIL. METHODS: We performed a pooled analysis of previously published cases. RESULTS: We identified 105 symptomatic patients in 33 families. Vascular risk factors were uncommon, with hypertension reported in only 8 patients. The mean age of symptom onset was 36. 7+/-12.9 years. Stroke or transient ischemic attack was an initial symptom in 45 patients, with a mean age of onset of 41.2+/-9.2 years. Migraine was also a common initial symptom, reported by 42 patients at a younger mean age of 28.3+/-11.7 years. Other initial symptoms included depression in 9 patients, cognitive impairment in 6 patients, and seizures in 3 patients. Regarding clinical course, 71 patients experienced a stroke or transient ischemic attack, and 52 of those patients had 1 or more recurrent ischemic events. Dementia was reported in 44 patients. Only 3 additional patients experienced migraine at a later time, while 13 additional patients developed depression. Six patients had seizures. Twenty-two of the 105 patients had died, with a mean age of death of 54.8+/-10.6 years. Nineteen of those 22 patients had experienced a stroke or transient ischemic attack and 19 patients were demented. CONCLUSIONS: CADASIL typically becomes evident in early or middle adulthood with migraine or an ischemic event, later manifests itself through recurrent subcortical ischemic strokes leading to a stepwise decline and dementia, and results in reduced survival.

Adolescent↗
PubMed1998

Prospective magnetic resonance imaging identification of focal cortical dysplasia, including the non-balloon cell subtype.

The purpose of this study was to determine the role of high-resolution T2-weighted fast multiplanar inversion-recovery (FMPIR) magnetic resonance (MR) imaging in detecting and delineating microscopic focal cortical dysplasia (FCD). We performed MR scans with FMPIR on 42 patients with suspected neocortical epilepsy. Ten MR studies were read prospectively as showing FCD; these case histories, electroencephalographic studies, and neuroimaging data were reviewed. Eight of these patients subsequently underwent focal cortical resection guided by intraoperative electrocorticography. The MR findings were correlated with pathological findings in these 8 patients. For purposes of radiological-pathological correlation, the FCD lesions were divided into two classes. Radiological classification was based on the absence (type A) or presence (type B) of T2 prolongation of the subcortical white matter. Pathological grading as type I or type II was based on a previously described pathological grading system. Specific MR findings associated with FCD included focal blurring of the gray-white matter interface (n = 9), thickening of the cortical ribbon (n = 7), and T2 prolongation of the subcortical white matter (n = 4). In 3 patients, the only MR finding that suggested FCD was localized blurring of the gray-white matter junction. In 2 of these 3 patients, the MR diagnosis of FCD could be made only by FMPIR. FCD was confirmed histologically in 7 of 8 patients, with insufficient tissue for complete histopathological evaluation in 1 case. Radiological classification of FCD agreed with pathological classification in 5 of 7 cases. Correlation of MR findings with intraoperative electrocorticography results indicated that the MR study localized the epileptogenic lesion correctly in 8 of 8 cases. Scalp ictal electroencephalographic studies localized the epileptogenic lesion in 5 of 8 cases; positron emission tomographic scans were focally abnormal in 3 of 3 cases. FMPIR MR imaging permitted accurate diagnosis and localization of FCD in all patients with pathologically proved FCD. MR identification of FCD aided presurgical planning and intraoperative management of these patients.

Adolescent↗
PubMed1998

CADASIL in a North American family: clinical, pathologic, and radiologic findings.

OBJECTIVE: To expand the reported phenotypic range of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). BACKGROUND: Despite numerous patient reports, our knowledge of the phenotypic range of CADASIL remains incomplete. METHOD: We performed clinical, pathologic, and radiologic examinations on members of a family with CADASIL. RESULTS: The proband is a 61-year-old man with a history of migraine and depression who has experienced multiple subcortical infarctions resulting in a stepwise decline. Neuropsychological testing documented a dementia syndrome with frontal lobe features and neurologic examination noted a left hemiparesis and a right-sided palmomental reflex. Brain biopsy with light microscopy revealed a nonatherosclerotic small-vessel angiopathy with periodic acid-Schiff positive granular changes in the media and white matter gliosis, with unremarkable cortex. Genetic testing confirmed a Notch3 mutation. The proband's first cousin has a history of depression, one seizure possibly resulting from an acute stroke, and a learning disorder. Neuropsychological testing demonstrated deficits in executive function and neurologic examination noted persistent extraneous adventitial movements, poor coordination, and primitive reflexes. Skin biopsy with electron microscopy demonstrated granular osmiophilic material within the basement membrane of vascular smooth muscle cells, which is considered to be pathognomonic of CADASIL. The proband's older son and younger son have histories of migraine and depression, respectively, and both also had learning disorders. MRI revealed diffuse white matter disease extending into the temporal lobes, and lacunar infarctions in these four nonhypertensive patients. Other family members have experienced migraine, recurrent stroke, dementia, and depression. CONCLUSIONS: CADASIL is a genetic basis for vascular dementia that may be manifest earlier in life than previously reported.

Adult↗
PubMed1997

Assembly properties of amino- and carboxyl-terminally truncated neurofilament NF-H proteins with NF-L and NF-M in the presence and absence of vimentin.

To understand the assembly characteristics of the high-molecular-weight neurofilament protein (NF-H), carboxyl- and amino-terminally deleted NF-H proteins were examined by transiently cotransfecting mutant NF-H constructs with the other neurofilament triplet proteins, low- and middle-molecular-weight neurofilament protein (NF-L and NF-M, respectively), in the presence or absence of cytoplasmic vimentin. The results confirm that NF-H can coassemble with vimentin and NF-L but not with NF-M into filamentous networks. Deletions from the amino-terminus show that the N-terminal head is necessary for the coassembly of NF-H with vimentin, NF-L, or NF-M/vimentin. However, headless NF-H or NF-H from which the head and a part of the rod is removed can still incorporate into an NF-L/vimentin network. Deletion of the carboxyl-terminal tail of NF-H shows that this region is not essential for coassembly with vimentin but is important for coassembly with NF-L into an extensive filamentous network. Carboxyl-terminal deletion into the alpha-helical rod results in a dominant-negative mutant, which disrupts all the intermediate filament networks. These results indicate that NF-L is the preferred partner of NF-H over vimentin and NF-M, the head region of NF-H is important for the formation of NF-L/NF-H filaments, and the tail region of NF-H is important to form an extensive network of NF-L/NF-H filaments.

Base Sequence↗
PubMed1996

Reversible signal abnormalities in the hippocampus and neocortex after prolonged seizures.

PURPOSE: To investigate the phenomenon of reversible increased signal intensity of medial temporal lobe structures and cerebral neocortex seen on MR images of six patients with recent prolonged seizure activity. METHODS: After excluding patients with known causes of reversible signal abnormalities (such as hypertensive encephalopathy), we retrospectively reviewed the clinical findings and MR studies of six patients whose MR studies showed reversible signal abnormalities. MR pulse sequences included T2-weighted spin-echo coronal views or conventional short-tau inversion-recovery coronal images of the temporal lobes. RESULTS: All six MR studies showed increased signal intensity within the medial temporal lobe, including the hippocampus in five studies. All follow-up MR examinations showed partial or complete resolution of the hyperintensity within the medial temporal lobe and the neocortex. In one patient, results of a brain biopsy revealed severe cerebral cortical gliosis. Temporal lobectomy performed 4 years later showed moderate cortical gliosis and nonspecific hippocampal cell loss and gliosis. CONCLUSION: Significant hyperintensity within the temporal lobe is demonstrable on MR images after prolonged seizure activity, suggestive of seizure-induced edema or gliosis. Damage to medial temporal lobe structures by prolonged seizure activity indicates a possible mechanism of epileptogenic disorders.

Adolescent↗
PubMed1995

Translation initiation and assembly of peripherin in cultured cells.

The peripherin gene has three potential ATG translation initiation sites at positions 38, 56, and 290. The second ATG has been proposed to be the initiation codon used for translation of the protein, but there is no experimental evidence for this conjecture. We have isolated a full-length peripherin cDNA (designated as p61-11) from a rat brain cDNA library. Upon sequencing, we found that this cDNA contains a point mutation at the second potential translation initiation codon, which changes this ATG to ACG. When expressed in SW13 cl.2 vim- cells, a cell line without any detectable cytoplasmic intermediate filaments, the protein product of p61-11 cannot form a filamentous network and the major product is 45 kDa in size, which is most likely initiated from the third ATG. The protein product from the first ATG (57 kDa in size) of p61-11 is also detected albeit in smaller amounts. We introduced a frame-shift mutation upstream of the third ATG in p61-11 to create p61-11FS and showed that the third ATG is able to initiate translation efficiently even in the presence of the first ATG, and the 45 kDa protein leads to a diffuse nonfilamentous staining pattern in vim- cells confirming that the first ATG may not be the preferred translation initiation codon, since it cannot suppress a downstream ATG. We increased the translation efficiency from the first ATG of p61-11 by mutating the three nucleotides preceding this first ATG and thereby placing it in a better Kozak consensus sequence for translation initiation. The resulting 57 kDa protein is able to form a filamentous network in vim- cells. We corrected the mutation in the original p61-11 by polymerase chain reaction and generated two peripherin constructs: perM1M2 (which contains all three translation initiation codons) and per delta 1M2 (the first ATG is deleted, but the other two are present). When transfected, their protein products, about 57 kDa in size, form filamentous networks in the absence of other cytoplasmic intermediate filaments. Since there is no 45 kDa protein detected for these latter two constructs, it is reasonable to conclude that in the presence of the second ATG, little or no translation is initiated from the third ATG. Taken together, these results strongly suggest that the second ATG is the preferred translation initiation codon for the peripherin gene.

Adenocarcinoma↗
PubMed1993

Migration of newly generated neurons upon ependymally derived radial guide cells in explant cultures of the adult songbird forebrain.

The adult songbird forebrain undergoes neuronal production throughout adulthood, with the production of new neurons in discrete regions of the neostriatal ventricular zone. Upon mitogenesis, these new neurons migrate into the subjacent brain parenchyma along radially directed guide fibers. In long-term ventricular zone explant cultures, derived from the higher vocal center of the adult canary, newly migratory neurons were found to associate preferentially with a characteristic substrate cell type. These small, parvonuclear substrate cells formed tightly packed epithelioid sheets, in which ciliated ependymal cells were common, as recognized by both live observation and electron microscopy. A subpopulation of these cells was immunostained by monoclonal antibody 3A7, which preferentially stains the guide fiber network of the adult avian brain. These 3A7+ cells included ependymal cells and bipolar radial cells, as well as morphologically defined astrocytes. As they matured in vitro, the 3A7+ bipolar radial cells extended long, unbranching fibers, which ultimately traversed the culture substrate. Like ependymal cells, they supported neuronal migration. These cells were likely homologous to radial guide cells in vivo. Thus, neuronal migration in adult avian forebrain culture occurred upon guide cells of ependymal derivation.

Animals↗
PubMed1991

Characterization of a panel of neurofilament antibodies recognizing N-terminal epitopes.

Peptides corresponding to sequences from the amino-terminal "head" regions of the low, middle, and high molecular weight neurofilament proteins (NF-L, NF-M, and NF-H) were synthesized by a modification of the Merrifield solid-phase method, and a panel of polyclonal antibodies to these epitopes were prepared in rabbits by the injection of synthetic peptides conjugated to the carrier protein keyhole limpet hemocyanin (KLH). An additional, monoclonal antibody recognizing both glial fibrillary acidic protein (GFAP) and vimentin was also produced, by fusion of cells of the mouse myeloma line NS-1 with spleen cells from a mouse immunized with cytoskeletal extracts. Antibody specificities were confirmed by a combination of Western blotting against cytoskeletal extracts and immunofluorescence using both rat brain sections and fibroblasts transfected with fully encoding cDNAs for each neurofilament protein, driven by viral promoters.

Amino Acid Sequence↗