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Biomedical subjects

Y Kishimoto

Publications and source records attributed to Y Kishimoto.

At least 307 records · Page 17Linked to original sources
PubMed1980

New phenotypic variant of adrenoleukodystrophy. Pathologic, ultrastructural, and biochemical study in two brothers.

Adrenoleukodystrophy is not usually considered in the differential diagnosis of the infantile onset of failure to thrive with motor and intellectual retardation. Rather, symptoms have started in childhood and have progressed over some years; not all patients have had overt adrenocortical insufficiency. The two brothers reported here developed symptoms in the neonatal period. In each the nature of the primary cerebral disorder was not recognized, because other etiologic factors clouded the diagnostic studies. In the younger brother, Case 1, a high titer (1:256) for cytomegalovirus (CMV) led to the suspicion that CMV infection accounted for the neurologic and ophthalmologic findings. Progressive neurologic deterioration at the age of 6 years prompted brain biopsy to confirm the diagnosis of progressive CMV encephalitis. In the older brother, Case 2, hemogenic hydrocephalus due to traumatic birth injury was held responsible for the psychomotor retardation and cerebral palsy. At necropsy, the adrenal glands in both cases were severly atrophic. In Case 1, a markedly inflammatory leukodystrophic process affected chiefly the frontal centra semiovalia and internal capsules, with relative sparing of parieto-occipital white matter and subcortical U-fibers. Heavy lymphocyte and monocyte cuffs surrounded many blood vessels in the white matter, and oil-red-O and PAS-positive macrophages were scattered in the zones of myelin disintegration and loss. Focally, the leukodystrophic process was so intense that cavitation necrosis was present, especially in the internal capsules. Further, PAS-positive, striated macrophages were aggregated in large clusters in liver, spleen, and lymph nodes. At the ultrastructural level, linear and gently arced, parallel, coapted or widely separated leaflets measuring 3-4 nm in width were identified in macrophages of the brain biopsy and in autopsy liver and lymph node. Biochemical analysis of fresh, frozen autopsy brain demonstrated cholesterol esters with long-chain fatty acids by thin-layer and gas-liquid chromatography. In Case 2, the leukodystrophic process could be readily identified in the brainstem and cerebellum but was masked in the cerebral hemispheres by the extensive hydrocephalus. The adrenal glands were atrophic and at light microscopy revealed adenomatoid nodules, many ballooned coritcal cells and very rare cells with striated cytoplasm. Masses of PAS-positive macrophages were encountered in liver and lymph nodes. In both cases, only old Wallerian degeneration of the corticospinal tracts was found in the spinal cord.

Adrenal Cortex↗
PubMed1980

Effects of a glucoside-hydrolase inhibitor (Bay g 5421) on serum lipids, lipoproteins and bile acids, fecal fat and bacterial flora, and intestinal gas production in hyperlipidemic patients.

Significant decrease in serum very low density lipoproteins and low density lipoproteins was observed after Bay g 5421 trial (300 mg/day for 6 weeks) in 14 hyperlipidemic patients. Although no significant changes were demonstrated in serum fractions of bile acids, the alteration in the patterns of fecal bacterial flora including the increase in obligate anaerobes was observed after the trial and this was accompanied by the increase in fecal fat excretion. Thus, the possible change in the intestinal bile acid metabolism with the altered flora may lead to an increased catabolism of cholesterol and to the reduction of serum low density lipoproteins. The meteorism developed in several patients but its etiology was shown to be independent of the patterns of the pre-trial bacterial flora and diet composition.

Acarbose↗
PubMed1980

[Trigeminal neurinoma with massive extracranial extension, report of a case (author's transl)].

It appears that more than a hundred cases of trigeminal neurinomas have hitherto been reported, but massive extracranial extension of a benign neurinoma into the sphenoid sinus and soft part tissue of the neck is unusual. A 36-year-old woman was admitted to our clinic with complaints of left blindness, vertigo and left nasal stuffiness. Neuroradiological examinations, including plain craniography, angiography and CT, showed a huge mass which destroyed the left middle fossa and extended into the left sphenoid sinus and soft part tissue of the neck. On December 14, 1978, left fronto-temporal craniotomy was carried out, and intracranial portion of the tumor was removed, leaving its extracranial portion intact. Pathological examination revealed benign neurinoma. The postoperative course was uneventful except temporary left total ophthalmoplegia. It was emphasized that, to obtain cure for trigeminal neurinoma, early diagnosis is extremely important, and, for this purpose, CT, including coronal one, was considered to be one of the most useful examinations.

Adult↗
PubMed1979

Fatty acid alpha-hydroxylation and its relation to myelination.

alpha-Hydroxylation is an enzymatic reaction by which long-chain fatty acids are converted to their alpha-hydroxy derivatives. This reaction, in animals, can be detected only in developing brain and is the rate-determining step in the synthesis of hydroxycerebroside, which is an indispensable and abundant myelin lipid. In addition to a particulate fraction from brain, two cytoplasmic factors, one heat-stable and the other heat-labile, are required for alpha-hydroxylation. During the past eight years we have been investigating alpha-hydroxylation. Our progress is summarized and discussed here.

Aging↗
PubMed1979

Conversion by rat brain preparation of lignoceric acid to ceramides and cerebrosides containing both alpha-hydroxy and nonhydroxy fatty acids. Effects of compounds which affect sphingolipid metabolism.

Three synthetic compounds which affect sphingolipid metabolism in vitro were examined for their effects on the synthesis in a rat brain system of nonhydroxyceramide, hydroxyceramide, nonhydroxycerebroside, and hydroxycerebroside from [1-14C]ignoceric acid. These compounds are N-octanoyl-D-threo-p-nitrophenylaminopropanediol (Compound I), N-(2,3-epoxydecanoyl)-norephedrine (Compound II), and N-decyl-N'-glucosylthiourea (Compound III). In the presence of up to 0.5 mM Compound I, only the hydroxyceramide fromation increased, while the synthesis of the other three lipids decreased. Compound II strongly inhibited the formation of all four lipids at all concentrations tested (0.1 to 1 mM). Compound III increased the synthesis of both ceramides approximately 2-fold at 1 mM, but the conversion of lignoceric acid to both cerebrosides remained relatively unchanged. Several significant conclusions from these observations are discussed.

Animals↗
PubMed1979

Synthesis of ceramides and cerebrosides containing both alpha-hydroxy and nonhydroxy fatty acids from lignoceroyl-CoA by rat brain microsomes.

The conversion of [1-14C]lignoceroyl-CoA to nonhydroxy- and alpha-hydroxyceramides and cerebrosides by brain microsomes of developing rat in the presence of NADPH was investigated. A new technique of thin layer chromatography for the separation of these lipids and unreacted substrate was developed for this assay. The synthesis of nonhydroxy- and hydroxyceramides was significantly stimulated by the addition of heat-stable factor, a factor which is essential in the alpha-hydroxylation of free lignoceric acid (I. Singh and Y. Kishimoto, manuscript in preparation). The addition of sphingosine also stimulated the ceramide synthesis to a great extent. When the microsomes or heat-stable factor were crude, the ceramides formed were further converted to cerebrosides, apparently by UDP-galactose contamination. The purification of these subcellular components resulted in the formation of only ceramides which, in turn, were converted to cerebrosides by the addition of UDP-galactose. These observations indicate that hydroxyceramide is the precursor of hydroxycerebroside and is formed by alpha-hydroxylation of lignoceroyl-CoA and N-acylation of sphingosine. However, lignoceroyl-CoA, like free lignoceric acid, does not appear to be the immediate substrate of the alpha-hydroxylation.

Acyl Coenzyme A↗
PubMed1979

Ceramide metabolism in brain.

Ceramide is the fundamental structure and key intermediate of all sphingolipids. Biosynthesis and catabolism of brain ceramide, especially their relationship to the metabolism of more complex sphingolipids in brain, are reviewed. Human genetic diseases which involve altered ceramide metabolism are also discussed.

Animals↗
PubMed1979

Endoneurial lipid composition of normal human sural nerve.

The endoneurial lipid composition was determined in 7 human sural nerves from subjects without known neurological disease. The nerves were morphologically normal, with myelinated fiber density of 7,710 +/- 1,210/mm2 (mean +/- SD). Endoneurium contained 30.7 +/- 1.5 mg total lipid per 100 mg of dry weight. Cholesterol was the predominant lipid (9.1 +/- 1.0 mg). Cholesterol ester was present only in very small quantities (0.2 +/- 0.1 mg). Cerebroside concentration was 4.5 +/- 0.3 mg, and sulfatide was 1.5 +/- 0.3 mg. The most abundant phospholipid was sphingomyelin (4.3 +/- 0.3 mg), followed by phosphatidylethanolamine (4.1 +/- 0.2 mg), phosphatidylcholine (3.8 +/- 0.2 mg), and phosphatidylinositol-phosphatidylserine (1.7 +/- 0.2 mg). Eighty-one percent of cerebroside nonhydroxy fatty acids were long chain (C20 to C26), and 67% were saturated. Technological advances now permit microchemical lipid analysis of human sural nerve biopsies in cases of neuropathy. When compared with our normative data, such studies may further the understanding of peripheral nerve disorders.

Adolescent↗
PubMed1979

Nerve lipid abnormalities in human diabetic neuropathy: a correlative study.

To study endoneurial lipid composition in human diabetic neuropathy, we biopsied sural nerves from 3 middleaged men with adult-onset diabetes mellitus. Magnitude of electrophysiological abnormalities and myelinated fiber loss paralleled the clinical severity of neuropathy in all cases. Cholesterol ester concentration was elevated to about 800% of normal in diabetic nerves. Reduction in total endoneurial lipid concentration correlated best with decrease in myelin volume as calculated from measured fiber diameters. Cholesterol, cerebroside, and most phospholipids were reduced in keeping with the severity of fiber loss in each nerve. The phosphatidylinositol-phosphatidylserine fraction was most reduced in the least affected nerves. Cerebroside nonhydroxy fatty acids in diabetic nerves were of shorter chain length and more saturated than normal. It is not yet clear whether the abnormalities of phosphatidylinositol-phosphatidylserine and cerebroside fatty acids are of pathogenetic importance or whether these changes may be the nonspecific consequence of axonal degeneration.

Adult↗