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Biomedical subjects

E S Cho

Publications and source records attributed to E S Cho.

71 records · Page 4Linked to original sources

Continual breakdown and regeneration of myelin in progressive multiple sclerosis plaques.

Plaques with lipid macrophages and macrophages containing undigested myelin fragments from five multiple sclerosis patients were studied by light microscopy of epoxy-embedded tissue (five cases) and electron microscopy (one case). Cell counts determined electron microscopically revealed that oligodendrocytes were reduced in number in areas of commencing myelin breakdown. The major mechanism of myelin destruction was phagocytosis by macrophages of intact myelin sheaths in the presence of very small numbers of lymphocytes and plasma cells. When plaques were orientated to allow examination of whole myelin internodes, it was found that most lesions, including lesions known to have been present for less than ten months, contained remyelinating internodes, sometimes in numbers large enough to form shadow plaques. It is concluded that the two processes of sometimes massive remyelination and active demyelination frequently coexist in "fatty" subacute plaques filled with lipid-containing macrophages, and that myelin breakdown at the edges of progressive lesions includes destruction of remyelinating internodes.

Adult↗

Effect of essential fatty acid deficiency on the epidermal sphingolipids of the rat.

The epidermal sphingolipids from rats maintained on either a rat stock diet or a fat-free diet have been analyzed. Thin-layer chromatographic analyses have revealed glucosylceramides, acylglucosylceramides and four fractions of ceramides, one of which proved to be an acylceramide. The relative amounts of the glucosylceramides, acylglucosylceramides and acylceramides were increased in the essential fatty acid-deficient epidermis while one ceramide fraction was diminished. The other two ceramide fractions remained unchanged. The acylceramides and acylglucosylceramides from normal rat epidermis both contained long-chain omega-hydroxy acids in amide linkage to sphingosine bases and high proportions of linoleic acid in ester linkage. The linoleate, which is known to be crucial for the formation and maintenance of the epidermal water barrier, was replaced by oleate in the essential fatty acid-deficient rats.

Animals↗

Neurotoxicology of vincristine in the cat. Morphological study.

Vincristine is a vinca alkaloid widely utilized in cancer chemotherapy. Its major clinical limitation is due to a drug induced sensory-motor neuropathy, the pathogenesis of which is poorly understood. This communication describes the morphological basis of a vincristine neuropathy in cats. Major pathological lesions were focal axonal swellings (giant axon formations) due to malaligned accumulations of neurofilaments and secondary demyelination of the paranodal type. These were primarily confined to the proximal portions of the peripheral nerves. The distal portions of the peripheral nerves contained only a few giant axon formations. Wallerian degeneration was noted to involve a small number of nerve fibers in the distal regions.

Animals↗

Tissue glutathione as a cyst(e)ine reservoir during fasting and refeeding of rats.

Previous reports suggest that liver glutathione serves as a cyst(e)ine reservoir in both starved rats and rats fed a cyst(e)ine-deficient diet. We investigated whether glutathione concentrations in other tissues also decrease and whether component amino acids of glutathione increase under such conditions. Tissue glutathione and free amino acid concentrations were measured in six groups of growing rats (120-150 g; four animals/group) during fasting and refeeding regimens. All animals were fed a rat stock diet ad libitum for 5 days. Two groups were than fasted for 24 or 48 hours, respectively. Other groups were fasted for 48 hours and then refed for 10, 24 or 48 hours respectively the stock diet. Significant changes (P less than or equal to 0.05) in liver and intestine glutathione concentrations were noted with 24 and 48-hour fasting, and a 24-hour refeeding was necessary to return concentrations to prefasting values. Muscle glutathione concentrations decreased slightly with fasting, but remained low with refeeding. Erythrocyte glutathione concentrations were independent of dietary treatment. Liver cysteine and glycine concentrations increased after 24 hours' fasting, but glutamate levels were not affected. The data indicate that liver and intestine glutathione serve as cyst(e)ine reservoirs during fasting. Since erythrocyte and muscle glutathione levels did not decrease, levels in these tissues cannot be used to measure cyst(e)ine status in premature infants fed parenterally.

Animals↗

Neurotoxicity of quelamycin in the rat.

Male Sprague-Dawley rats were given a single dose of 10 or 20 mg/kg quelamycin intravenously and perfusion fixed at 4, 12, 28 and 48 days after drug administration. Light microscopical study of 1 micrometer thick sections of dorsal root ganglia revealed focal regions of neuronal nuclear clearing involving 40-50% of neurons at 4 days. There was subsequent progressive reduction in the incidence of such lesions. Neuronal necrosis apparently affecting less than one percent of dorsal root ganglia neurons was noted initially at 12 days in the 20 mg/kg group and 28 days in the 10 mg/kg group. Comparison of these findings with previous studies indicated that quelamycin was less neurotoxic to rats than its parent compound adriamycin.

Animals↗

Subacute motor neuronopathy: a remote effect of lymphoma.

Ten patients developed a subacute lower motor neuron syndrome as a remote effect of Hodgkin's disease or other lymphoma. The illness usually followed a benign course independent of the activity of the underlying neoplasm. Seven of the patients improved spontaneously, and 3 became neurologically normal. Two patients died of intercurrent infections related to immunosuppression. Neuropathological examination of these 2 patients and 3 previously reported cases showed prominent neuronal degeneration restricted to the anterior horns of the spinal cord and mild posterior column demyelination. Demyelination was also present in the anterior roots of our autopsied patients and was accompanied by large, hyperchromatic Schwann cells. The cause of the illness is obscure, but both radiation therapy and opportunistic infection may be contributing factors. Attempts at virus isolation have been unsuccessful. The syndrome should be distinguished from the more common direct effects of lymphoma on the nervous system, since its identification spares the patient additional, potentially harmful therapy.

Adult↗

Utilization of D-methionine during total parenteral nutrition in postsurgical patients.

Utilization of intravenously administered D-methionine was measured by morbidly obese subjects fed parenterally after elective gastric bypass surgery. Five patients were infused with a 25% glucose--4.25% amino acid solution containing DL-methionine, and four were treated with a 25% glucose--3.5% amino acid solution containing only L-methionine. Mean (+/- SD) total daily methionine excretion was 0.06 +/- 0.04 mmoles (of 28 +/- 4 mmoles infused) in patients treated with the L-methionine containing solution, and was 15.2 +/- 4.2 mmoles/day (of 45.2 +/- 5 mmoles DL-isomer infused) in patients treated with the DL-methionine containing solution. In these latter patients, 90 to 98% of the excreted methionine was the D-isomer. The data indicate 64 +/- 23% of infused D-methionine is excreted in the urine. Four patients excreted between 70 to 85% of infused D-methionine in the urine, but one patient excreted only 35 to 55%, suggesting better utilization. Plasma methionine levels were higher (9.9 +/- 1.9 mumoles/100 ml) in patients infused with solutions containing DL-methionine than those infused with the L-methionine solution (4.5 +/- 1.0 mumoles/100 ml). In the former case, 49% of plasma methionine was the D-isomer. The data indicate poor D-methionine utilization by postsurgical patients during total parenteral nutrition when given as DL-methionine in the presence of other amino acids and glucose.

Adult↗

D-Methionine utilization during parenteral nutrition in adult rats.

D-Methionine, present in some parenteral solutions, is poorly utilized by man. To evaluate some of the factors affecting utilization, methionine isomer excretion was measured in rats treated with two different parenteral regimens: total parenteral nutrition and protein sparing therapy. Within each regimen, nutrient solutions differing only in methionine isomer composition were compared. Eight rats on the total parenteral nutrition regimen were infused with a 33% glucose--2.8% amino acid solution at a rate providing 100% of energy requirement. Four rats received the parenteral sulution containing L-methionine, and four the solution containing DL-methionine. Eight additional rats on a protein sparing regimen were infused with an amino acid solution (8.5%) at a rate to provide 25% of energy requirement. Four rats were infused with a solution containing L-methionine, and four with a solution containing DL-methionine. Total methionine content of livers was not affected by differences in methionine isomer. Infusion of the solution containing DL-methionine significantly increased plasma methionine levels during protein sparing therapy, with the increase representing accumulation of the D-isomer. Rats receiving protein sparing therapy had significantly higher liver methionine levels than rats receiving total parenteral nutrition. Although rats infused with the solution containing DL-methionine had elevated plasma methionine levels during protein sparing therapy, urinary methionine losses were small, as were losses of methionine sulfoxide and alpha-keto-gamma-methiolbutyrate. In contrast to humans, adult rats utilized more than 99% of parenterally administered D- or L-methionine.

Animals↗

Position sensitivity of de-efferented muscle spindles in experimental acrylamide neuropathy.

An experimental neuropathy was induced in cats by injections of acrylamide (7.5, 15 or 30 mg/kg/day) for 2 to 10 days. The responses of primary and secondary endings of soleus muscle spindles to stretch were evaluated and correlated with the appearance of ataxia and incoordinated motor movements. Animals that received 15 or 30 mg/kg/day became ataxic and demonstrated poor motor coordination on the 7th or 4th day, respectively. At these times, both primary and secondary endings of muscle spindles had elevated thresholds and diminished discharge frequencies. Continued acrylamide administration resulted in exacerbation of the clinical symptoms and further attenuation of spindle responses. The discontinuation of acrylamide was followed by slow recovery. Only those cats which received a total dose of 75 mg/kg or less remained asymptomatic and had normal spindle function. The coincidence of onset of motor coordination deficits and spindle dysfunction, coupled with a lack of demonstrable motor defect at the same time, suggests that the initial clinical features of acrylamide neuropathy may be partly the consequence of impaired spindle function.

Acrylamides↗

Toxic effects of adriamycin on the ganglia of the peripherial nervous system: a neuropathological study.

Rats were injected intravenously with 10 mg/kg of adriamycin (doxorubicin). All the treated animals developed severe posterior limb ataxia on days 11 and 12 following the injection. Mild ataxia of the forelimbs was noted later. The animals were killed between days 10 and 50. Light microscopy revealed changes in ganglion cells of the peripheral nervous system with sparing of neurons in the central nervous system. In the spinal, paravertebral and trigeminal ganglia, necrosis of neurons was followed by mild lymphocytic infiltration, and ultimate loss of ganglion cells, and a marked proliferation of nerve sheath cells. Electron microscopic study revealed increased numbers of neurofilaments and the presence of membrane-bound cisterns in the affected dorsal root ganglion cell bodies. It is concluded that adriamycin, an important anticancer therapeutic agent, has neurotoxic properties and that it selectively damages the ganglia of the peripheral nervous system.

Animals↗

HTLV-III/LAV-like retrovirus particles in the brains of patients with AIDS encephalopathy.

It has been postulated that the retrovirus HTLV-III/LAV thought to be the etiologic agent of AIDS also infects the central nervous system and directly causes AIDS encephalopathy. Electron microscopical studies performed on brain sections from three patients with AIDS complicated by progressive encephalopathy revealed structures morphologically consistent with HTLV-III/LAV retrovirus particles. The particles were located principally within multinucleated giant cells but were also present in astrocytes. Many particles were also noted in the extracellular space.

Acquired Immunodeficiency Syndrome↗

D-methionine utilization in young miniature pigs, adult rabbits, and adult dogs.

Rats and chickens, unlike man, utilize D-methionine efficiently. We have studied urinary excretion of methionine isomers in young miniature pigs, adult rabbits, and adult dogs given D-methionine in an attempt to find an animal model that, like man, utilizes the D-isomer poorly. Six-week-old miniature pigs ingesting a protein-free diet were infused with 8.5% amino acid solutions differing only in methionine isomer content (L- vs DL-) to supply amino acid requirements. Each solution was infused for a 2- or 3-day period in a cross-over design. Plasma methionine levels were significantly higher (p = 0.01) during infusion of the solution providing DL-methionine, with 25% of total plasma methionine present as the D-configuration. However, urinary methionine excretion was similar with both solutions, with D-methionine utilization calculated as greater than 99%. Adult rabbits ingesting DL-methionine (0.14 g/100 g food) showed good utilization of D-methionine, excreting less than 1.3% D-isomer in the urine. Mixed breed dogs given 1.25 g D-methionine in their drinking water excreted less than 0.4% of ingested D-methionine in the urine. These data indicate that the pig, rabbit, and dog utilize D-methionine efficiently, behaving like the rat and chicken rather than man.

Amino Acids↗

Neurotoxicity of adrimycin in rats: a low-dose effect.

A neurotoxic effect of Adriamycin in rats has been noted following a single iv dose level of 5 mg/kg of body weight (35 mg/m2 of body surface area). The changes which were studied in the dorsal root ganglia were qualitatively similar to those previously reported at a higher dose level. The early changes involved neuronal nuclei and included focal regions of clearing and altered staining of chromatin. Necrosis of many affected neurons followed, but the evolution of this lesion was slower than that seen in previous studies using the higher dose of the drug.

Animals↗