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Biomedical subjects

S E Kornguth

Publications and source records attributed to S E Kornguth.

At least 37 records · Page 2Linked to original sources
PubMed1987

Magnetic resonance imaging of gadolinium-labeled monoclonal antibody polymers directed at human T lymphocytes implanted in canine brain.

Two different murine monoclonal anti-human T cell antibodies, that were coupled to gadolinium (Gd), bind specifically to human T lymphocyte cells implanted in canine brain. This binding was at a concentration of Gd sufficient to detect the implanted cells and to distinguish them from the surrounding brain tissue with magnetic resonance imaging (MRI) at a field strength of 1.5 Tesla. These Gd-labeled immunoglobulin preparations did not bind bovine T cells at a concentration sufficient to be detected on MRI. A protein solution containing the immunoglobulins (100 micrograms), gelatin (2 mg), and bovine serum albumin (2.5 mg) was reacted with the dianhydride of diethylenetriaminepentaacetic acid (DTPA); the DTPA serves as a metal chelator and as a protein crosslinking agent. The DTPA-protein complex was reacted with Gd chloride. There were approximately 10 DTPA residues per protein molecule in the modified protein mixture. Isolated human or bovine monocytes (approximately 12 million cells) were implanted in the brains of anesthetized dogs in a volume of 40 microliters. The blood-brain barrier was then disrupted by the intra-arterial injection of hyperosmotic mannitol, and the Gd-labeled antibodies were injected through a catheter placed at the branch of the internal and external carotid arteries. The brains were imaged 48 to 72 hours later. The MRI scans revealed a markedly decreased T1 relaxation time with a high signal intensity (TE = 25 msec, TR = 200 msec) related to the human T cell implants. There was no evidence of decreased T1 at the site of the bovine T cells. Neither control murine gamma globulin coupled to Gd-DTPA nor anti-human T cell antibodies uncoupled to Gd modified the MRI contrast of the human T cells in the brain.

Animals↗
PubMed1986

Visual field defects in cats with neonatal or adult immunological loss of retinal ganglion cells.

Behavioral perimetry methods were used to assess the monocular visual fields of 12 cats that had received intraocular injections of antibodies against large (alpha/Y) retinal ganglion cells. The antibodies produced defects in head and eye orientation responses to stimuli presented in the nasal visual field of the treated eye; responses to stimuli in the temporal visual hemifield were normal. Similar results were seen in cats that received antibody injections at 4 weeks of age or as adults. In the context of previous results, these findings suggest that a loss of Y cells in the lateral geniculate nucleus is sufficient to reduce geniculocortical function for head and eye orientation to visual stimuli in the nasal visual field.

Animals↗
PubMed1986

Contributions of Y- and W-cell pathways to response properties of cat superior colliculus neurons: comparison of antibody- and deprivation-induced alterations.

The cat's superior colliculus (SC) receives direct inputs from retinal W-cells (a W-D input) and Y-cells (Y-D input) and an indirect Y-cell input via the lateral geniculate nucleus and visual cortex (Y-I input). In previous studies we have shown that intraocular injection of antibodies raised against large retinal ganglion cells produces a dose-dependent reduction in the Y retinogeniculate pathway. Furthermore, when a sufficiently high antibody concentration is used, there is a substantial loss of the Y pathway and no apparent loss of the W pathway. In the present study, we used the antibodies to investigate the contributions of the Y and W pathways to functional organization within the SC. Binocular injections of low (330 micrograms/100 microliters) or high (1,000 micrograms/100 microliters) antibody concentrations were made. The antibody-mediated effects on SC cells' response properties were compared directly with effects of early binocular deprivation, which have been attributed to a loss of Y-I input. Extracellular single-cell recordings were made from the SC, and cells were classified as receiving Y-D, Y-I, or W-D inputs on the basis of their response latencies to electrical stimulation of the optic chiasm and optic tract. Injections of the low antibody concentration produced no significant effects on inputs to the SC. However, injections of the high antibody concentration resulted in a 70% reduction in SC cells with a Y-D input and an 82% reduction in SC cells with a Y-I input. There was no effect on the percentage of cells with a W-D input. Binocular deprivation produced a 76% reduction in the percentage of cells with Y-I input. Visual response properties of SC cells also were assessed. Injections of the high antibody concentration produced a 55% reduction in cells that respond with a directional preference and a 51% reduction in cells that respond to high-velocity stimuli. Binocular deprivation produced a 78% reduction in the proportion of directional cells and a 25% reduction in cells that respond to the ipsilateral eye. Taken together, the results of this and previous studies using cortical lesions, visual deprivation, and immunoablation suggest that Y-D input is the primary basis for responses to high stimulus velocity, Y-I input is an important basis for directional responses and response through the ipsilateral eye, and W-D input is important for responses to low stimulus velocity.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1986

Anti-neurofilament antibodies in the sera of patients with small cell carcinoma of the lung and with visual paraneoplastic syndrome.

The sera of patients with small cell carcinoma of the lung (SCCL) and an associated visual paraneoplastic syndrome (VPNS) have high titer immunoglobulins that react with retinal ganglion cells and with cloned lines of the SCCL. The immunoglobulins in the sera of two patients with SCCL and VPNS reacted with at least one common antigen shared by neural cells and cloned lines of the SCCL. The molecular weights of the predominant neural and tumor antigens were 205,000, 145,000, 65,000, and 20,000-24,000 as determined by Western blots. Three of the antigens from neural tissue copurify and comigrate electrophoretically with neurofilament proteins. Polyclonal antibodies prepared against authentic neurofilament proteins react with antigens having molecular weights identical to those of proteins that react with immunoglobulins from the SCCL-VPNS patients. Polyclonal antibodies that were prepared against isolated retinal ganglion cells and that were shown previously to cause the immunoablation of the ganglion cells in vivo reacted most intensely with the Mr 205,000 antigen and weakly with the Mr 145,000 and Mr 70,000 antigens. Treatment of the Western blots with alkaline phosphatase from Escherichia coli did not affect the immunoreactivity between the immunoglobulins and the purified neurofilament proteins. It is proposed that the immunoglobulins in the sera of patients with SCCL-VPNS may be involved etiologically in the development of the VPNS.

Animals↗
PubMed1986

Dose-response analysis of effects of antibodies to large ganglion cells on the cat's retinogeniculate pathways.

Previous studies have shown that antibodies against large retinal ganglion cells (alpha-/Y-cells) reduce the Y-cell retinogeniculate pathway while having little or no effect on the X- or W-cell pathways. The present study investigated the dose-response relationship of these effects. We began by studying effects on the T1 (largely Y-cell-mediated) and T2 (largely X-cell-mediated) waves of the retinal field-potential. Different concentrations of the antibodies were injected intraocularly in adult cats and retinal field-potentials evoked by optic chiasm stimulation were examined. The lowest concentration of immune serum tested (330 micrograms/100 microliter volume) reduced both the T1 and T2 amplitudes. With increasing concentrations, the ratio of T1:T2 amplitudes progressively decreased from 0.71 to only 0.05. The highest concentration of immune serum tested (1000 micrograms/100 microliter volume) virtually eliminated the T1 wave while the T2 wave remained (albeit reduced). Next, we carried out single-cell physiological and morphological studies to verify the effects of the highest antibody concentration and compare them with previous results on effects of the lowest antibody concentration (Kornguth et al., 1982; Spear et al., 1982). In single-cell recordings from the retina, the encounter rates of Y- and X-cells were reduced by 85 and 53%, respectively, after injection of the highest antibody concentration. There was no effect on the encounter rate of retinal W-cells. After injection of the lowest antibody concentration, there was no change in the encounter rates of any of the retinal cell types. Morphological studies revealed an 88-99% loss of alpha-cells in retinae treated with the highest antibody concentration. There also was a substantial (24-57%) loss of medium-size ganglion cells but no loss of small ganglion cells. The loss of alpha-cells was much greater after high-concentration injections than after low-concentration injections. In recordings from the LGN, the proportion of Y-cells was reduced by 87% in laminae receiving input from an eye injected with the highest antibody concentration. Laminae receiving input from an eye injected with the lowest concentration had a 77% reduction in Y-cells. The encounter rate of LGN X-cells was not affected by either concentration. Morphological analysis indicated that the loss of Y-cells in the LGN was not due to changes in cell size. These findings indicate that antibody-mediated effects on retinogeniculate pathways are dose-dependent.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1985

Selectivity of antibody-mediated destruction of axons in the cat's optic nerve.

The purpose of this study was to determine the selectivity with which polyspecific antibodies directed against large retinal ganglion cells destroy axons in the cat's optic nerve. Immune serum prepared against large ganglion cells isolated from ox retinas was injected into 1 eye of each of 2 cats. After more than 1 month, the cats were perfused with mixed aldehydes and the optic nerves were prepared for transmission electron microscopy. On the basis of a large sample of micrographs of transverse thin sections, we estimated that each of the nerves that issued from treated eyes contained approximately 62,500 necrotic fibers, amounting to 42-46% of the total fiber population in 1 case and 39-42% in the other. The diameters of 2900-5000 intact axons from each of 4 nerves (2 from immune-treated eyes and 2 from untreated eyes) were measured. Comparisons of histograms of axon diameter for nerves from treated and untreated eyes revealed that 90-100% of large axons with diameters above 3.5-4.0 micron were eliminated by the antibodies. Between 65 and 70% of medium-sized fibers were also eliminated. The number of small axons--those with diameters less than 1.2-1.6 micron--did not differ appreciably from normal. These results suggest that the immune serum destroyed virtually all alpha cell axons and a substantial fraction of beta cell axons but did not reduce the number of small fibers that largely stem from the gamma class of retinal ganglion cells.

Animals↗
PubMed1985

Autoimmune basis for visual paraneoplastic syndrome in patients with small-cell lung carcinoma.

Unexplained neurological disorders sometimes develop in patients with cancer, even when the primary tumour or its metastases have not invaded the central nervous system. Visual dysfunction in patients with small-cell carcinoma of the lung is one of these paraneoplastic syndromes and is associated with serum auto-antibodies which react with specific subsets of retinal neurons. These sera have now been shown to react with cell lines derived from small-cell carcinoma. The antibodies recognise a small number of antigens shared by retinal and tumour cells, suggesting that an autoimmune response may be triggered by the tumour.

Aged↗
PubMed1982

Occurrence of anti-retinal ganglion cell antibodies in patients with small cell carcinoma of the lung.

This report describes a patient with small-cell carcinoma of the lung associated with blindness. The serum of this patient was tested for immunoreactivity with retinal sections because there was no evidence of tumor metastasis to the central nervous system and because neuroendocrine cells of the lung share common antigens with retinal neurons. The immunoglobulins in the sera from this patient, from two other patients with small-cell carcinoma, from two patients with multiple sclerosis and from three controls were reacted with 8 micrometers thick sections of retina. Dog, cat and human retinal sections were used. Antihuman immunoglobulins that were conjugated to horseradish peroxidase were used as the second antibody to identify the cells which bound the patients' immunoglobulins. A high titer (1:500) antibody level against retinal ganglion cells was found in the patient with small-cell carcinoma and blindness; the antibody reaction was similar with retina from the three species. The large ganglion cells bound the immunoglobulins of the patients with small-cell carcinoma and blindness while the immunoglobulins from the control and multiple sclerosis subjects did not bind these cells selectively at high dilutions. It remains to be shown whether these antibodies have an etiologic significance in the development of blindness.

Aged↗
PubMed1982

Reduction in numbers of large ganglion cells in cat retina following intravitreous injection of antibodies.

Antibodies were prepared against large ganglion cells isolated from bovine retina and injected into the vitreous chamber of 1 eye in 6 adult cats. The other eye of each cat received either a control pre-immune gamma-globulin injection or was untreated. After a survival time of 9-86 days, ganglion cell density was assessed from Nissl-stained retinal whole-mounts. In each cat, there were fewer large ganglion cells (alpha-cells) in the immunoglobulin-injected retina than in the control retina. The reduction in large ganglion cells occurred in patches adjacent to areas of approximately normal large ganglion cell density. Counts of the number of large ganglion cells in both eyes of the 6 cats indicated that the immunoglobulin injected eyes had from 8% to 61% (mean 32%) fewer large ganglion cells than the paired control eyes. This was significantly greater than the difference in the number of large ganglion cells between pairs of normal or control-injected eyes. The magnitude of the effect was not related to the survival time following the immunoglobulin injection. Cell size measures of all ganglion cells in selected areas of retina indicated that the small ganglion cells were unaffected by the antibodies. However, there was a suggestion that the largest of the medium size ganglion cells were affected in addition to the large ganglion cells. Counts of total ganglion cells per unit area in affected regions of retina revealed a reduced overall density, suggesting that the ganglion cells were lost rather than decreased in size. These results indicate that antibodies to the large ganglion cells can be used to reduce the number of large ganglion cells (alpha-cells) in the cat retina. Since these cells correspond to the Y-cell functional class of ganglion cells in the cat retina, the antibodies may provide a useful tool for studying Y-cell function in the visual pathways.

Animals↗
PubMed1980

Familial infantile myasthenia.

Familial infantile myasthenia is a rare type of myasthenia that usually occurs in connection with respiratory depression. The condition is characterized by (1) absence of myasthenia in the mother, (2) occurrence of a similar disorder among siblings, (3) respiratory depression at birth, (4) episodic weakness and apnea during the first two years of life, and (5) improvement with age. Since the condition responds to anticholinesterase medication, early diagnosis is important. Familial infantile myasthenia is a potential cause of sudden infant death and should be considered in infants with unexplained respiratory distress.

Adolescent↗
PubMed1979

Impeded cerebellar development and reduced serum thyroxine levels associated with fetal alcohol intoxication.

Pregnant albino rats were placed on a complete liquid diet (Ensure) containing either 9% ethanol or an isocaloric amount of sucrose between the third and twentieth day of gestation. The pups born to these rats were sacrificed either day 11 or day 14 postnatum and morphometrical, histological and biochemical analyses were done on their cerebellums and cerebrums. Pups that were exposed to ethanol in utero had significantly smaller body weights, cerebrums and cerebellums than pair-fed controls. The cerebellar mass was reduced by 10% and the cerebral weight by 3% in the pups exposed to alcohol when body weights were normalized to that of pair-fed controls. Cerebellar aspartyl aminotransferase (EC 2.6.1.1) activity was reduced at day 11 and 14 in ethanol treated pups compared with controls. Serum T4 levels were also reduced in the ethanol treated group. Histological analyses revealed that the external granule cell (EGC) layer of ethanol treated pups was significantly thicker at 11 and 14 days postnatum than that of pair-fed control pups. Cerebellar ornithine decarboxylase (ODC, EC 4.1.1.17) activity was higher at day 11 in the ethanol treated pups than in controls. The reduced mass, AAT activity, T4 serum levels and the increased thickness of the ECG layer indicate a delayed or impeded maturation of cerebellum in ethanol treated pups. These data are considered from the viewpoint that ethanol, other drugs such as methadone and prenatal stress (malnutrition) may cause delayed cerebellar maturation by reducing serum T4 levels in the early postnatal period (day 5-14).

Alcohol Drinking↗
PubMed1975

Isolation and partial characterization of a tubulin-like protein from human and swine synaptosomal membranes.

Synaptic membranes from human and swine brains were solubilized with 8 M urea and the proteins were reduced and alkylated. A protein was isolated from both sources and had identical amino acid compositions and molecular weights as determined by electrophoresis on polyacrylamide-sodium dodecylsulfate gels and by ion-exchange chromatography and gel filtration on Bioglas 1000. The apparent molecular weight of the protein was 53 000 on the acrylamide-sodium dodecylsulfate gels. Neither neutral sugars nor sialic acid was a significant component of the protein. When the proteins were digested with trypsin and the resultant peptides subjected to chromatography (n-butanol/acetic acid/water) and electrophoresis (pH 3.7) the peptide maps were identical. The protein comprises 1-2 percent of the total synaptosomal protein. With regard to amino acid composition, molecular weight, peptide map characteristics, behavior on DEAE-cellulose columns, electrophoretic mobility and sugar content, the synaptic protein is quite similar to the monomer of swine tubulin.

Amino Acid Sequence↗