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Biomedical subjects

D Schiffer

Publications and source records attributed to D Schiffer.

At least 73 records · Page 4Linked to original sources

Parkinson's disease mortality in Italy, 1951 through 1987. Analysis of an increasing trend.

Parkinson's disease mortality was analyzed in Italy for the period from 1951 through 1987. The adjusted mortality was 4.27 and 2.77/100,000 population, respectively, for men and women. Adjusted rates increased in both sexes (63% increase in men and 80% in women in 1983 through 1987 vs 1951 through 1952). Age-specific mortality increased in subjects aged over 75 years and decreased in those under 64 years. The analysis by birth cohorts demonstrated higher rates in the cohorts born between 1890 and 1910 than in those born before and after that period. Even if these changes in Parkinson's disease mortality might reflect better case ascertainment and the increase of life expectancy of patients with Parkinson's disease, there is some evidence that the temporal variation is associated with the changing experiences of different birth cohorts.

Age Factors↗

Proliferating cell nuclear antigen expression in brain tumors, and its prognostic role in ependymomas: an immunohistochemical study.

Proliferating cell nuclear antigen (PCNA)/cyclin is currently often investigated immunohistochemically in tumors as a marker of cell proliferation, but many problems remain open concerning its reliability as a prognostic factor. PCNA has been studied in a series of 123 brain tumors using the monoclonal antibody PC10. A clear intra- and inter-tumor variability of PCNA-positive nuclei has been found, but taking into account the tumor areas with the highest number of positive nuclei, a positive correlation between this number and the histological malignancy of tumors has been demonstrated. The staining intensity of nuclei was variable; very-intensely positive nuclei, counted separately, are hypothesized to represent nuclei in S-phase of the cell cycle. In ependymomas the investigation included a quantitative statistical analysis. The number of PCNA-positive nuclei correlated with cell density and mitotic index, but only very intensely positive nuclei showed a significant statistical correlation with survival. In spite of the many possibilities of wrong interpretation of PCNA expression, the most important of which is its deregulation, the method is useful in the practice for prognostic purposes. Its important advantages are the possibility of a retrospective application and a visual analysis of the proliferation potential of tumors.

Antigens, Neoplasm↗

Motor neuron disease with pallido-luysio-nigral atrophy.

A case of motor neuron disease (MND) with pallido-luysio-nigral atrophy (PLNA) is reported. The 45-year-old male patient presented with lower motor neuron symptoms and signs of basal ganglia disturbance. He died after a progressive course of 7 months. Neuropathological examination revealed motor neuron loss at all spinal cord levels with sparing of Onuf's nucleus. Nerve cell loss and gliosis were also present in substantia nigra, globus pallidus, and subthalamic nucleus. The presence of ubiquitin-positive inclusions, a hallmark of most variants of MND, confirms this case as an example of MND. At immunoelectron microscopy the granules were distributed on filamentous material. The combination of clinically apparent PLNA with MND has only been described twice previously. The relationship of this syndrome to other forms of MND and its nosological placement are discussed.

Atrophy↗

Immunohistochemistry of glial reaction after injury in the rat: double stainings and markers of cell proliferation.

The astrocytic reaction in the rat after brain injury has been studied immunohistochemically for intermediate filaments (GFAP and vimentin), also with double staining procedures, and for markers of proliferation (BrdU and PCNA). GFAP-positive reactive astrocytes appeared around the lesion, where they were vimentin-positive and at a distance. BrdU and PCNA showed a high labelling index around the wound at day 2 and scattered positive nuclei were also found at a distance in the ipsilateral side. BrdU-positive astrocytes represented a minor fraction of GFAP- and vimentin-positive astrocytes. The expression of vimentin persisted at least 15 days after the lesion. Our results could suggest that distant reactive astrocytes originate through hypertrophy while those close to lesion arise by hyperplasia from mature or immature glial cells. The hypothesis is formulated that cells of the periventricular matrix contribute to the post-traumatic proliferative activity.

Animals↗

Early onset cerebellar ataxia with retained tendon reflexes: prevalence and gene frequency in an Italian population.

A genetic epidemiologic analysis of early onset cerebellar ataxias (EOCA) with retained tendon reflexes was performed in a defined area of Northwestern Italy. Forty cases diagnosed from 1940 to 1990 were ascertained. The ascertainment probability was 85.7%. The segregation analysis (Weinberg's proband method and 'singles' method under incomplete ascertainment) is compatible with autosomal recessive inheritance. The point prevalence ratio was 1.0/100,000 population. The birth incidence rate was 1/48,000 live births. Gene frequency was estimated to be 1/218. The ratio of first-cousin marriages among parents of EOCA (4.5%) was lower than expected using Dahlberg's formula (8.9%).

Adolescent↗

Reduced life expectancy in 40 cases of early onset cerebellar ataxia with retained tendon reflexes: a population-based study.

A survival analysis of 40 cases of early onset cerebellar ataxia (EOCA) with retained tendon reflexes was performed. They represent all cases of EOCA diagnosed between 1945 and 1990 among residents of a defined area of Northwestern Italy, followed up to December 31, 1990. The survival rates were respectively 92%, 87% and 77% at 10, 20 and 30-years, worse than expected in a disease which is usually considered benign. The relative death rate was 4 times higher than expected for the general population. Prognosis was significantly worse for males than for females, whereas the age of onset and the calendar year of onset did not affect survival.

Adolescent↗

Monoclonal antibodies to keratan sulfate immunolocalize ramified microglia in paraffin and cryostat sections of rat brain.

We used six monoclonal antibodies (MAb) recognizing epitopes within keratan sulfate (KS) chains for an immunocytochemical study of adult rat brain. One of the MAb selectively stained microglia and their ramified processes. KS-positive cells were found throughout the CNS in both paraffin-embedded and cryostat sections; the greatest number were present in hippocampus and brainstem. In the cortex the positive processes of some cells surrounded neuronal somata. In the white matter the processes were both parallel and perpendicular to the axon bundles. Double staining showed that KS-positive cells did not express astrocytic or oligodendroglial markers. By immunoelectron microscopy, the positivity was localized around the perikarya and cell processes of small cells with peripheral chromatin clumps and dark cytoplasm, which often contained secondary lysosomes. The KS-positive cells did not contribute to myelin sheaths and were not surrounded by a basal membrane. In addition to the cellular staining, three other MAb stained the white matter diffusely. Anti-KS MAb are therefore proposed as immunohistochemical markers for ramified microglia in both paraffin and cryostat sections of adult rat brain.

Animals↗

Amyotrophic lateral sclerosis mortality in Italy, 1958 to 1987: a cross-sectional and cohort study.

We analyzed the mortality rates of amyotrophic lateral sclerosis (ALS) in Italy from 1958 to 1987. The overall mean annual mortality rate, adjusted to the 1981 Italian population, was 0.68/100,000 (95% confidence interval, 0.64 to 0.72); 0.86 for men; and 0.62 for women. During that period, mortality increased for both sexes: from 1958/1962 to 1983/1987, mortality increased by 60% for women and 24% for men. The slope for women was 0.07, and for men, 0.02. Moreover, the mortality rate increased in older age groups and was stable for subjects under 45 years old. There was no clear birth-cohort effect, but in any cohort the age-specific mortality rate increased with advancing age, with no decline for the oldest age. Based on these data, the increase of ALS mortality rates is probably due to the effect of changing methodologic and demographic variables and the decrease of mortality of some competing diseases, rather than a real rise of the risk in the whole population or in specific birth cohorts.

Adult↗

Is polar spongioblastoma a tumor entity?

The distribution of cells in a parallel fashion with palisades of nuclei is common in neuroepithelial tumors. The authors have selected 16 such tumors from their series for study, as examples of different neuroepithelial oncotypes containing palisades of nuclei: three ependymomas, three hemispheric pilocytic astrocytomas, three oligodendrogliomas, three medulloblastomas, three cerebellar astrocytomas, and one central neuroblastoma. In two additional tumors, affecting a 12-year-old girl and a 51-year-old woman, this feature was present in the entire surgical specimen and the diagnosis was consistent with a polar spongioblastoma. This diagnosis applies in the literature to rate tumors of childhood and adolescence, both malignant and with embryonal features. In one specimen, a clear ependymomatous feature was found in a remote area of the tumor and in the other there were ultrastructural characteristics of neuroblastoma. Nuclear palisades can be found as local architectural features in many neuroepithelial tumors. The rare tumors diagnosed as polar spongioblastoma, according to published criteria, correspond to ependymomas and neuroblastomas. Polar spongioblastoma does not exist as a tumor entity.

Astrocytoma↗

Selective expression of the Met/HGF receptor in human central nervous system microglia.

The c-MET proto-oncogene encodes the tyrosine kinase receptor for hepatocyte growth factor (HGF), also known as scatter factor, a powerful mitogen and motility factor for epithelial cells. We now show that the two previously described forms of the Met/HGF receptor, the intact p190MET and the truncated p140MET, are expressed in physiological conditions in the human central nervous system (CNS). The receptors were identified by Western blot analysis with monoclonal antibodies directed against different epitopes. By immunohistochemical staining the Met/HGF receptor was found to be expressed in a homogeneous cell population, equally distributed between the grey and the white matter, showing morphological features and immunochemical markers specific for the resident microglial cells. These data suggest a possible role for the c-MET proto-oncogene and HGF in microglial reactions to CNS injuries.

Antibodies, Monoclonal↗

Peripherin immunoreactive structures in amyotrophic lateral sclerosis.

BACKGROUND: Increased levels of the neuron-specific intermediate filament, peripherin, have been recently detected in regenerating motor neurons of rat spinal cord after nerve transection. No data are yet available on peripherin expression in normal and diseased human spinal cord. EXPERIMENTAL DESIGN: We have investigated the presence of peripherin immunoreactive structures in routinely processed spinal cord of human patients with amyotrophic lateral sclerosis and control cases by immunohistochemistry and immunoelectron microscopy. Adjacent sections were stained with antibodies to neurofilaments (NF) and ubiquitin. RESULTS: In control cases, immunoreactivity for peripherin was found in neurons of dorsal root ganglia, in the posterior columns, in dorsal and ventral roots, and in scattered age-related axonal swellings. The cytoplasms of motor neurons were unstained. In amyotrophic lateral sclerosis cases most spheroids were immunoreactive for NF and to a lesser extent for peripherin. A few spheroids were strongly reactive for peripherin and were only weakly stained by antibodies to NF in adjacent sections. Both antibodies to NF and peripherin failed to demonstrate structures corresponding to the intraneuronal filamentous inclusions labeled by ubiquitin. CONCLUSIONS: The accumulation of peripherin and NF in spheroids is likely related to the reduced anterograde transport. Alternatively, the spheroids showing a higher degree of peripherin immunoreactivity might represent regenerating axonal terminals.

Aged↗

Immunohistochemical observations on rat radial glia: relationship with the origin of ethylnitrosourea-induced tumors.

Gliomas induced in the rat by transplacental administration of ethylnitrosourea (ENU) are intensely immunoreactive for vimentin and scarcely for glial fibrillary acidic protein (GFAP). Since tumoral transformation takes place during the late fetal and early postnatal period, the sequential expression of the two glial antigens has been investigated in this age period in ENU-treated and control rats. Immunohistochemical and immunoelectron microscopical methods have been employed. Vimentin was widely expressed starting from embryonal day 14 (E 14) in the processes of radial glia; as long as radial glia was present, vimentin decorated it. GFAP was, at earliest, observed at E 20 and expressed by glial cells with a stellate, i.e., mature shape. No GFAP-positive radial process was observed. No difference was found between ENU-treated and control rats. Since ENU is most effective in producing tumors when administered at the 16-17th day of fetal life, vimentin-positive radial glia is a candidate target of ENU. The similarity of intermediate filament pattern between radial glia in the late fetal life and tumors induced by transplacental ENU suggests that radial glia might be the cell of origin.

Animals↗

LR Gold embedding of nervous tissue for immunoelectron microscopy studies.

A major drawback of all acrylic resins commonly used for post-embedding immunocytochemical studies of the central nervous system is the disruption of the ultrastructural morphology, due to the high lipid content of neural tissue. We have investigated the suitability of the acrylic resin LR Gold, which has been employed recently for immunogold labeling studies in several non-neural tissues. Optimal preservation of both antigenicity and ultrastructure of nervous tissue was obtained after en bloc staining with uranyl acetate, followed by total dehydration in acetone and curing at low temperature. Cell membranes and myelin sheaths, which are usually lost with other acrylic resins, were well maintained. The degree of antigenicity of LR Gold-embedded tissues was comparable to that of LR White-embedded one, but the morphologic detail was much better preserved. The use of LR Gold is particularly advantageous for studying neurodegenerative disorders such as Alzheimer disease.

Acrylic Resins↗

Medullomyoblastoma: report of two cases.

Two cases of medullomyoblastoma in children are described. The muscular component showed different features in the two cases and were associated with neuronal differentiation. Morphological, immunohistochemical, and electron microscopical findings are presented. The origin of the muscular component is discussed in relation to the findings in other cases of the literature. Both differentiation from primitive neuroepithelial cells and derivation from ectomesenchyme are considered.

Biomarkers, Tumor↗

Selective intra-arterial chemotherapy with BCNU in recurrent malignant gliomas.

Study of intra-arterial BCNU in 12 patients with recurrent glioblastoma multiforme and 5 patients with recurrent anaplastic astrocytoma already treated by surgery and radiotherapy indicates that the risk of BCNU toxicity can be reduced by the use of relatively low doses (160-180 mg/m2) of BCNU, the use of dextrose as solvent, selective injections of BCNU, and fast "bolus" injections of drug. No certain toxic effects of BCNU were observed in the 17 patients treated this way. Anaplastic astrocytomas, particularly in young patients, seem to respond relatively well to this treatment.

Adult↗

Age-related ubiquitin deposits in dystrophic neurites: an immunoelectron microscopic study.

Widespread neuritic dystrophy is a hallmark of Alzheimer's disease (AD) and, in a less severe form, of brain ageing in various mammalian species. By immunohistochemistry, diffuse dot-like staining for ubiquitin (Ubq), a polypeptide involved in the degradation of abnormal and short-lived proteins, has been associated with human brain ageing. The nature of the Ubq deposits was investigated by immunogold electron microscopy on autopsy samples from aged human and dog brains. Most of the dot-like staining was localized to the white matter and corresponded to myelinated dystrophic neurites filled by Ubq-labelled lysosomal dense bodies. They did not contain paired helical filaments or multilamellar bodies. A minority of Ubq deposits was represented by amorphous densities in focal enlargements of the myelin sheaths. Our findings show that the spectrum of Ubq changes in ageing brain is wider than formerly recognized, and support the hypothesis that a defective regulation of the lysosomal system might be involved in the pathogenesis of structural abnormalities both in the ageing brain and in Alzheimer's disease.

Aged↗

Accuracy of death certificate diagnosis of amyotrophic lateral sclerosis.

STUDY OBJECTIVE: The aim was to determine the reliability of official mortality statistics in estimating long term trends of amyotrophic lateral sclerosis (ALS) in Italy. DESIGN: The study was a mortality follow up of cases of ALS. SETTING: Piedmond Region, northern Italy. SUBJECTS: Cases of ALS were identified from multiple sources between 1966 and 1985. MAIN RESULTS: Cause of death was determined for the cases who died between 1970 and 1985. Death certificates were obtained in 488 out of 510 cases (95.7%). ALS was mentioned in 365 (74.8%) of cases. The most frequent erroneous diagnoses were multiple sclerosis and malignant tumours. Demographic variables, such as sex, age at death, province of death, and calendar year of death, did not influence the percentage of true positive cases significantly. CONCLUSIONS: The death certificate diagnosis of ALS appears to be adequate for use in descriptive and analytical epidemiology.

Adult↗

Prion protein mutation at codon 102 in an Italian family with Gerstmann-Sträussler-Scheinker syndrome.

We present the first family from Italy with the Gerstmann-Sträussler-Scheinker syndrome (GSS) and a substitution of leucine for proline at codon 102 of the prion protein gene. This mutation is associated with the ataxic form of GSS in a number of reported families. The clinical presentation of our family includes amyotrophic changes in some affected family members in addition to ataxia.

Adult↗