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Biomedical subjects

H S Singer

Publications and source records attributed to H S Singer.

At least 55 records · Page 3Linked to original sources
PubMed1986

Diffuse leptomeningeal seeding from a malignant spinal cord astrocytoma in a child with neurofibromatosis.

A 5-year-old child typical clinical features of neurofibromatosis presented with a history of suspected basilar meningitis and CT findings of enlarged optic nerves and an expanding left cavernous sinus mass. CSF cytologies and meningeal biopsy were unremarkable. At craniotomy, a mass confluent with the left trigeminal nerve was resected which had histologic characteristics of a nerve sheath tumor but was GFAP (glial fibrillary acidic protein) stain positive. Postmortem examination, 1 month following surgical resection, demonstrated a clinically unsuspected primary thoracic spinal cord astrocytoma with dissemination throughout the subarachnoid space, invasion of the trigeminal nerve and encasement of other cranio-spinal nerves. This unusual case emphasizes the occurrence of leptomeningeal spread in a clinically silent spinal cord glioma and the diagnostic value of immunohistochemistry.

Brain↗
PubMed1986

Mouse chimeras composed of trisomy 16 and normal (2N) cells: preliminary studies.

Many humans with trisomy 21 (Down Syndrome (DS)) have psychomotor and cognitive retardation, congenital heart disease, and hematologic abnormalities. Partial genetic homology exists between mouse chromosome 16 and human chromosome 21; thus, studies of the development of mice with trisomy 16 (Ts16) may provide important insights into the pathogenesis of these defects and into the mechanisms by which they arise in humans. Since Ts16 mice do not survive the late fetal period, chimeras have been formed between Ts16 and normal (2N) mouse embryos to rescue the Ts16 cells for postnatal studies. In this preliminary study of the postnatal development of such chimeras, we examined the proportion of Ts16 cells in a variety of tissues, including the coat, blood, placenta, heart, and brain. The Ts16 cells made significant contributions to almost all tissues examined. Aspects of the behavior and the neurochemistry of adult Ts16 less than-greater than 2N chimeras were found to differ significantly from control (2N less than-greater than 2N) chimeras and from animals of the two donor embryo strains. Ts16 cells comprised a substantial, but not predominant, proportion of cells in each brain region examined. Suggestions for definitive analyses are reviewed.

Animals↗
PubMed1985

Niemann-Pick disease--type C. Ocular histopathologic and electron microscopic studies.

The presence of lipid storage was demonstrated in type C Niemann-Pick disease by histopathologic and ultrastructural studies. Pleomorphic membranous inclusions, with variable proportions of light and dark granular material, were observed within the conjunctival fibrocytes, endothelial cells and pericytes, keratocytes, lens epithelium, retinal ganglion cells, retinal pigment epithelium, fibrocytes in the uveal tract, and optic nerve fibrous astrocytes. Only optic nerve and retinal ganglion cell involvement had clinical counterparts represented by optic nerve pallor and perimacular gray discoloration.

Child↗
PubMed1985

A therapeutic trial of amniotic epithelial cell implantation in patients with lysosomal storage diseases.

To determine whether allografts of normal amniotic epithelium might provide a nonimmunogenic cellular source of exogenous lysosomal enzymes, subcutaneous implants of amniotic epithelium were performed in six children with clinically advanced storage diseases. The clinical and the biochemical status of each patient was observed for several weeks after amniotic epithelial cell implantation (AECI). Serial studies of blood samples from each patient in the post-AECI period did not demonstrate any increase in levels of deficient lysosomal hydrolase. In two patients, quantitative urinary excretion of substrate was also studied and did not show consistent alterations after AECI. No patient had objective improvement in clinical or neurodevelopmental status following AECI. Two patients died with progressive disease at 2 1/2 and 3 1/2 mo after AECI; no residual amniotic epithelium was found at postmortem examination. Four patients are alive with progressive disease at 6-14 mo after AECI. We conclude that allografts of normal human amnion do not provide sufficient replacement hydrolases for clinical or biochemical improvement in lysosomal storage diseases.

Amidohydrolases↗
PubMed1984

CSF cholinesterase activity in Gilles de la Tourette's syndrome.

Cerebrospinal fluid acetylcholinesterase (AChE) activity was studied as a possible marker for central cholinergic neuronal function in seven patients with Gilles de la Tourette's syndrome. No significant differences were found between CSF AChE activity in untreated or haloperidol-treated patients and control populations. These data do not appear to support a pathophysiologic association between the cholinergic system and Gilles de la Tourette's syndrome.

Adolescent↗
PubMed1984

Cerebrospinal metastases in malignant childhood astrocytomas.

Over a period of five years, antemortem diagnosis of leptomeningeal spread was made in six of thirteen children with high grade astrocytomas. These included four of seven children with hemispheral tumors and two of six children with malignant brainstem gliomas. Leptomeningeal spread was diagnosed by the clinical picture and CSF profile. Meningeal spread occurred an average of 5 months (range 0-16) after initial diagnosis of tumor was made. Several patients responded well to local radiation and/or chemotherapy. Mean survival after evidence of meningeal spread was 7 months (range 2-16) with one patient still alive. Meningeal spread of malignant childhood astrocytomas appears to be common and should be sought for in these patients as local radiation is beneficial. Serious consideration should be given to a controlled trial of prophylactic craniospinal radiation in three tumors. The role of chemotherapy also requires further study.

Adolescent↗
PubMed1984

GM1 gangliosidosis, type 2: ocular clinicopathologic correlation.

The clinical and pathological manifestations of a case of juvenile GM1 gangliosidosis are presented and the pathological findings compared with those previously reported for GM1 gangliosidosis in man and in animal models. The most striking finding in the present case was the marked degeneration of the retinal ganglion cell and nerve fiber layers. Although such extensive ganglion cell loss was not observed in any of the other cases reviewed, the presence of multimembranous inclusion bodies in retinal ganglion cells strongly suggests that the pathological process was similar in all cases. Much remains to be learned about the function of gangliosides in the healthy retina and about the pathophysiological consequences of deranged ganglioside metabolism. The many parallels, including those observed in pathological studies, between the human and animal forms of GM1 gangliosidosis allow an optimistic appraisal of the value of further research using the animal models.

Animals↗
PubMed1984

Morphologic and neurochemical studies of embryonic brain development in murine trisomy 16.

Telencephalic and diencephalic/brainstem regions from embryonic trisomy-16 mice (Ts16) between gestational days 15-18 were analyzed for alterations of morphologic and neurochemical parameters and compared to phenotypically normal littermates. Mean trisomic wet weights from both regions were significantly diminished (greater than 20%) and total protein content was reduced. Ratios of the thickness of the ventricular (germinal) zone to the thickness of the whole cortex were increased, suggesting a delay in neuronal differentiation. Pre- and postsynaptic markers for GABAergic, cholinergic, catecholaminergic and serotonergic transmitter systems were compared. A significant impairment of the trisomic brain catecholaminergic and serotonergic system development was observed, based upon regional reductions in norepinephrine, dopamine and serotonin content. Choline acetyltransferase activity in the diencephalon/brainstem was reduced by 21-26% in contrast to normal levels within the cerebral hemispheres. Presynaptic GABAergic markers were not affected in the Ts16 embryos. It is concluded that although a genetic imbalance involving chromosome 16 in the mouse embryo produces a delay in neurogenesis, it has a more selective effect on the catecholaminergic, serotonergic and cholinergic systems than on GABAergic neurons.

Amino Acids↗
PubMed1984

Synaptic neurochemical alterations associated with neuronal degeneration in an inherited cerebellar ataxia of Gordon Setters.

Canine Inherited Ataxia (CIA) is an autosomal recessive cerebellar disease of Gordon Setters associated with degeneration of Purkinje and granule cells. To define specific biochemical correlates of neuronal loss, synaptic neurochemical parameters were measured in three cerebellar regions (vermis, "pars intermedia," and hemisphere) at early and late stages of this disease. At one and a half years of age, affected dogs showed the most severe lesions in the "pars intermedia," with a 39% decrease in the number of Purkinje cells and a 29% decrease in granule cells. Neurochemical measurements demonstrated decreased [3H]muscimol binding and elevations in norepinephrine concentration (248% above control) and [3H]glutamate receptor binding (118% above control). At five years of age, reduction of Purkinje cells in the three cerebellar regions ranged from 65 to 91% while loss of granule cells was between 13 and 53%. [3H]Muscimol binding remained low throughout the cerebellum (38 to 59% of control) and norepinephrine concentration and [3H]glutamate binding were markedly reduced from the levels observed at one and a half years. Glutamate decarboxylase activity, [3H]QNB binding and GABA concentration were relatively unaffected. Our results indicate that neurochemical parameters associated with cerebellar neuronal systems demonstrate specific alterations in a chronic degenerative disorder. This study also indicates the importance of evaluating neurochemical measurements with regard to both spared and degenerating neuronal systems and emphasizes the role of compensatory neurochemical alterations in cerebellar degenerative disorders.

Animals↗
PubMed1983

Electrophysiological studies in Tourette's syndrome.

The value of standard electrophysiological studies using electroencephalography and evoked responses was evaluated in patients with Tourette's syndrome. Sixteen-channel electroencephalograms were obtained in 40 patients (36 males, 4 females) awake and asleep, and evoked responses were obtained in a subgroup of 17 patients. Evoked response variables evaluated included latencies and amplitudes of visual evoked responses, brainstem auditory evoked responses, and somatosensory evoked responses to median and peroneal nerve stimulation. Only 5 of the 40 patients (12.5%) demonstrated electroencephalographic abnormalities, which included central spikes, generalized and paroxysmal slow activity, and slowing of the normal basic frequency. Evoked response studies demonstrated no consistent differences between the patients with Tourette's syndrome and age- and sex-matched controls. The data demonstrate no notable diagnostic or therapeutic value for routine electroencephalographic or evoked response studies in Tourette's syndrome.

Adolescent↗
PubMed1982

Neurotransmitter chemistry in feline GM1 gangliosidosis: a model for human ganglioside storage disease.

Assays for synaptosomal high-affinity uptake activity (glutamate, gamma-aminobutyric acid, norepinephrine), neurotransmitter synthesizing enzymes (choline acetyltransferase, glutamate decarboxylase, tyrosine hydroxylase), and endogenous neurotransmitters were performed in cats with advanced inherited GM1 gangliosidosis. A significant reduction in uptake activity, ranging from 24 to 77% of control, was demonstrated in motor, occipital, and cerebellar brain regions. This reduction was unassociated with comparable alterations in neurotransmitter levels or synthesizing enzyme activity. We hypothesize that the defect of neurotransmitter inactivation is part of an overall abnormality of synaptic membrane function that could contribute to the neurological symptoms seen in the hereditary gangliosidoses.

Animals↗