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Y Kishimoto

Publications and source records attributed to Y Kishimoto.

At least 253 records · Page 14Linked to original sources

Metabolism of cerebrosides and sulfatides in subcellular fractions of developing rat brain.

Previous studies on myelinating rat brain indicated that microsomes, Golgi-enriched and cytosol fractions may process galactolipids destined for myelin. To extend these findings we labeled brain galactolipids in vivo and determined the specific radioactivity of cerebrosides and sulfatides in several subcellular fractions. 17-day-old rats were treated by intracranial injection with [14C]galactose 60 min prior to and [3H]galactose 15 min prior to killing. Subcellular fractions were prepared from brain stem, and concentrations of cerebrosides and sulfatides were determined, their radioactivity measured and the 3H/14C ratio compared. Our results showed that the heavier Golgi-enriched fraction (designated Fraction 2) is unique in its low galactolipid content and high specific radioactivities of cerebrosides and sulfatides. The low ratio of the specific activity of cerebroside to that of sulfatide in Fraction 2 compared to other fractions indicates that it may be the site of most rapid conversion of newly synthesized cerebrosides to sulfatides. The specific radioactivities of cerebrosides and sulfatides in cytosol are intermediate between those in Golgi-enriched Fraction 2 and microsomes and those in myelin, consistent with the role postulated for cytoplasmic elements in the transport of cerebrosides and sulfatides to myelin.

Animals↗

Changes in monogalactosyl diacylglycerols, alkylgalactolipids and cerebroside fatty acid esters in maturing rat brain measured by high-performance liquid chromatography.

A newly developed high-performance liquid chromatography method was used to measure four nonpolar glycolipids in developing rat brain. The accumulation patterns of nonhydroxy- and hydroxycerebroside fatty acid esters were similar to those of myelin cerebrosides. In contrast, both monogalactosyl diacylglycerol and alkylgalactolipids reached maximal levels at the early stages of myelination.

Aging↗

Plasma carcinoembryonic antigen and acinar cell carcinoma of the pancreas.

Seventeen patients with histologically proven pancreatic cancers were studied in order to clarify the relationship of histologic types to plasma carcinoembryonic antigen (CEA) values. Two cases with marked elevation of plasma CEA values having 6100 ng/ml and 2500 ng/ml, respectively, disclosed histologically acinar cell carcinoma and mixed acinar and ductal cell carcinoma, respectively. Despite of massive hepatic metastases, the other 15 cases with ductal cell carcinoma, including 3 cases with cystadenocarcinoma, adenoacanthoma, and undifferentiated pancreatic cancer, respectively, showed normal or very modest elevation of plasma CEA values. No correlation was obtained between plasma CEA values and several biochemical tests. Two patients with marked elevation of plasma CEA value revealed strong staining in the cancerous areas of the pancreas by using a peroxidase-antiperoxidase staining technique. These findings suggest that acinar cell carcinoma of the pancreas may contribute to increase the circulating plasma CEA value.

Adenocarcinoma↗

Alpha-hydroxylation and oxidation of lignoceric acid in brain: the role of heat-stable and heat-labile factors.

Our previous investigations disclosed that the heat-stable and heat-labile factors obtained from brain cytosol are required for alpha-hydroxylation and oxidation of lignoceric acid by rat brain particulate fraction. The heat-stable factor was recently found to contain glucose-6-phosphate, N- acetylaspartate , glutamate, aspartate, glutamine, inorganic phosphate and low levels of adenosine nucleotide as active components. A combination of these compounds was as effective as the crude heat-stable factor for enzymic activity. Using these compounds, we reinvestigated the requirement for the heat-labile factor. With crude heat-stable factor there was an absolute requirement for the heat-labile factor; however, with various combinations of the individual components of the heat-stable factor, some degree of activity was obtained without the heat-labile factor. When aspartate or one of its derivatives, N- acetylaspartate or oxaloacetate, was used in place of the heat-stable factor, the activity was relatively low but highly stimulated by the addition of heat-labile factor. On the other hand, higher activity was obtained when glutamate or one of its derivatives, glutamine or alpha-ketoglutarate, was used without heat-labile factor. The addition of heat-labile factor to this system did not stimulate the activity. When studying the aspartate family, we discovered that the requirement for the heat-labile factor varied in a descending order: N- acetylaspartate greater than aspartate greater than oxaloacetate. Lignoceric acid oxidation was further characterized with rat brain particulate fraction, NADPH, Mg2+, glutamate, inorganic phosphate, and AMP without heat-stable and heat-labile factors. It was found that the requirement for NADPH was also partially eliminated with glutamate but not aspartate. The effects of various inhibitors, such as inhibitors of the electron transfer system, oxidative phosphorylation, the enzymes involved in citric acid cycle, and glycolysis, suggest that the heat-stable factor is involved in producing ATP or other high energy compounds to be used for the activation of lignoceric acid. ATP added to the system in place of heat-stable factor resulted in less than one-half of the lignoceric acid oxidation.

Adenine Nucleotides↗

The lipid composition of urodele myelin which lacks hydroxycerebroside and hydroxysulfatide.

The concentrations of cerebrosides and sulfatides were measured in the nervous systems of urodeles and related orders with a high performance liquid chromatographic technique. The peripheral and central nervous systems of all three urodele species, Necturus maculosis (mud puppy, a salamander), Notophthalmus viridescens (eastern red spot newt), and Desmognathus ochropheus (mountain salamander), were found to be completely devoid of alpha-hydroxy fatty acid-containing cerebrosides and sulfatides. All species of reptiles and fish classes close to urodeles contain these galactolipids. The levels of nonhydroxy fatty acid-containing cerebrosides and sulfatides are essentially similar in both urodeles and reptiles. Myelin isolated from Necturus spinal cord had a specific density of 1.07, lighter than mammalian myelin. Except for the absence of hydroxycerebrosides and hydroxysulfatides, the lipid composition of Necturus spinal cord myelin is essentially similar to that of frog and rat myelin. The fatty acids of nonhydroxycerebrosides are rich in monounsaturated homologs of C22-C25, and the sphingoid base consists of both sphinganine and sphingosine. Electron microscopic examination of the sciatic nerve showed that the general structure and interlamellar distances of salamander and newt myelin are identical to those of frog, chameleon, and rat. Necturus myelin, therefore, can be used as a model for the study of the functional and structural role of hydroxygalactolipids.

Animals↗

Adrenoleukodystrophy: impaired oxidation of very long chain fatty acids in white blood cells, cultured skin fibroblasts, and amniocytes.

We compared the formation of 14CO2 from [I-14C]fatty acids in homogenates of cultured skin fibroblasts and white blood cells from 25 patients with adrenoleukodystrophy (ALD) and from 24 controls. The ALD group included 16 boys with childhood ALD, five men with adrenomyeloneuropathy (AMN), and two boys and two girls with neonatal ALD. The substrates were unbranched saturated fatty acids ranging in chain length from 16-26 carbons. From C24:0, the radioactive CO2 production by homogenates of ALD fibroblasts and white blood cells was 17% and 37% of control, respectively, and from C26:0 it was 17% of control in ALD fibroblasts. The CO2 evolution from palmitate (C16:0) in the ALD was identical to the control group; for C18:0, the value for ALD cells was 76% of control, and fatty acids with chain lengths between C18:0 and C24:0 gave intermediate results. Results for childhood ALD patients were similar to those for the AMN patients. More limited studies with cultured amniocytes of fetuses with childhood ALD gave results similar to those obtained with cultured skin fibroblasts, and results with neonatal ALD patients appeared to be the same as for childhood ALD and AMN. Studies of three women who were carriers for childhood ALD gave values intermediate between ALD and control. The total C26:0 levels in ALD cultured skin fibroblasts and white blood cells were 4-6 times that of control; the total C24:0 levels were increased 10-30%, whereas the C22:0 levels were unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Clinical studies of cefotaxime in infections in internal medicine].

Clinical studies on a new cephalosporin antibiotic, cefotaxime (CTX) were carried out in 79 patients with various types of infections in internal medicine. The efficacy rates were 65.8% in 39 cases of respiratory tract infections, 94.1% in 17 cases of biliary tract infections, 75.0% in 12 cases of urinary tract infections, 80.0% in 11 cases of other infections, and 75.3% in all cases. After CTX therapy, body temperature was improved in 76.7% of all 79 patients, particularly being excellent in all cases of biliary tract infections. Furthermore, symptoms such as cough, dyspnea, chest pain, moist rale and anorexia were improved to a great degree after CTX therapy. Adverse reactions and abnormal laboratory findings consisted of mild liver injury in 1 out of 79 cases. CTX was assessed to be an effective antibiotic for various types of infections in internal medicine.

Adult↗

Malignant mixed tumor of the liver in adults.

An extremely rare case of malignant mixed tumor of the liver in adults is reported. A 60-year-old man was admitted because of abdominal fullness. Abdominal CT-scan demonstrated a low density lesion surrounded by high density ring area in the liver. Liver scintigram and selective hepatic angiography revealed a malignant tumor mass which was indistinguishable from other malignant masses. Postmortem examination disclosed that histology of the liver tumor was Edmondson's grade II hepatocellular carcinoma and chondrosarcoma. There are no special clinical features of this tumor and the diagnosis is almost always made during exploratory laparotomy or at autopsy. However, abdominal CT-scan findings are somewhat helpful for diagnosis of malignant mixed tumor of the liver in adults.

Adenocarcinoma↗

An improved procedure for the quantitative determination and characterization of sulfatides in rat kidney and brain by high-performance liquid chromatography.

A significant improvement has been made in the desulfation step of our previously published HPLC determination of cerebrosides, sulfatides, and monogalactosyl diacylglycerols (Nonaka, G. and Kishimoto, Y., Biochim. Biophys. Acta 572 (1978) 423-431). Instead of the original two-phase reaction, a solution of trifluoroacetic acid in ethyl acetate is used for the solvolysis in the new method. The revised method was used to determine the levels of cerebrosides and sulfatides in rat kidney. Among four individual glycosphingolipids studied, hydroxysulfatide was present at the highest level (0.7-1.3 nmol/mg of dry tissue), followed by nonhydroxysulfatide (0.3-0.8 nmol/mg of dry tissue). Hydroxycerebroside (0.09-0.16 nmol/mg of dry tissue) and nonhydroxycerebroside (0.03-0.09 nmol/mg of dry tissue) were present in smaller quantities. There appear to be no significant differences between male and female animals of different ages (30-120 days), although the amounts decreased slightly in older animals and there was a higher concentration in female than in male kidney. Tissue size was significantly smaller in females. The homolog composition of rat kidney sulfatide was studied by reverse-phase HPLC, and was found to be significantly different from that reported in human kidney. Rat sulfatides contained fatty acids with a higher degree of saturation and longer chain length. Preliminary studies indicated that rat kidney contained unusually large quantities of C25:1 and C27:1 fatty acids and also that there was more C26:1 than C24:1 acid. In brain of the same animals the ratio of nonhydroxy to hydroxysulfatide decreased with age (1.5:1 in 30-day-old brain; 1:1 at 90 days).

Aging↗

Changes in nervous system glycolipids during metamorphosis of Xenopus laevis.

Qualitative and quantitative changes occurring in the myelin marker glycolipids, cerebrosides, sulfatides, and monogalactosyl diglyceride, in the nervous system (brain, spinal cord, and tail) of Xenopus laevis during its metamorphic stages were analyzed by normal and reverse-phase high performance liquid chromatography. The concentration of these glycolipids increased rapidly in brain until the tadpole reached the middle of metamorphosis, fluctuated slightly, decreased until metamorphosis was completed, and increased once more as the frog matured. Similar changes were observed in the spinal cord, but the decrease of glycolipids occurred at a later stage of metamorphosis. The glycolipid level in tail nerve reached a peak at the beginning of metamorphosis and then rapidly decreased. The ratios of hydroxycerebroside and hydroxysulfatide to respective nonhydroxylipids in brain, spinal cord, and tail remained constant throughout the metamorphic change but differed in each tissue. The tail contained the highest ratio. The glycolipids in sciatic nerve generated during the metamorphosis had an even higher hydroxyl lipid/nonhydroxy lipid ratio. The cerebrosides contained extremely high concentrations of monounsaturated fatty acids with very long carbon chains (C22-C25) and this homolog composition remained almost unchanged throughout metamorphosis. These results indicate that active degradation of these glycolipids, and probably of myelin, occurs but the glycolipid composition of myelin appears to remain the same throughout the metamorphic process. The significance of these findings is discussed from a morphological standpoint.

Animals↗

Sulfatide synthesis in mice with defective synthesis of 3'-phosphoadenosine 5'-phosphosulfate.

The regulation of sulfation of galactocerebroside was examined in several tissues from brachymorphic mice, including the central nervous system and kidney. These animals have an inherited defect in the enzymes which synthesize 3'-phosphoadenosine 5'-phosphosulfate (PAPS) resulting in decreased sulfation of glycosaminoglycans. In contrast, sulfation of galactocerebroside to form sulfatide (sulfogalactocerebroside) was normal in brachymorphic mice even in tissues with decreased ability to synthesize PAPS. This suggests that, unlike the regulation of glycosaminoglycan sulfation, the formation of sulfatide is not stringently regulated by tissue levels of PAPS.

Adenine Nucleotides↗

An unusual glucocerebroside in the crustacean nervous system.

High concentrations of glucocerebroside (glucosylceramide) were found in the ventral nerve cord, brain, optic nerve, and antenna, but not in the nonneural tissue, of the brown shrimp Penaeus aztecus aztecus. This lipid contained unusual sphingoid bases consisting of 14-, 15-, and 16-carbon sphinganines and sphingenines. The fatty acids were mainly nonhydroxylated homologs 22 carbons long and longer, similar to those found in galactocerebroside but differing from those in glucocerebroside in mammalian nervous systems.

Amphibians↗

Mechanism of the protective action of thiol compounds in ethanol-induced liver injury.

The protective action of cysteine or mercaptopropionylglycine (MPG) in acute ethanol-induced liver injury has been investigated in the rat. Cysteine accelerated clearance of ethanol and acetaldehyde from blood and liver and prevented an increase in hepatic content of triglyceride and serum ornithine carbamoyl transferase activity. MPG accelerated clearance of ethanol and acetaldehyde less efficiently but prevented an increase in these variables to the same degree. The mode of action of thiol compounds in acute ethanol-induced liver injury has been discussed.

Acetaldehyde↗

Further characterization of the heat-stable factor in the alpha-hydroxylation and oxidation of lignoceric acid in brain: effect of acidic amino acids and hexose-phosphates on brain fatty acid metabolism.

Lignoceric acid and other very long-chain fatty acids are converted to alpha-hydroxy fatty acids and ceramide in brain. These fatty acids are also oxidized and produce glutamic acid and other water-soluble products. All of these metabolic conversions are catalyzed by a rat brain particulate fraction and require NADPH, heat-labile factor, and heat-stable factor. The heat-stable factor was prepared from calf cerebellum. Glucose 6-phosphate and N-acetylaspartic acid have previously been identified as active components of the heat-stable factor. We report in this manuscript that glutamic acid, glutamine, aspartic acid, and gamma-aminobutyric acid as well as inorganic phosphate and adenosine nucleotides are also active components of the heat-stable factor. When the amino acids, glucose 6-phosphate, AMP, and phosphoric acid were combined, full activity of the heat-stable factor for the formation of cerebronate (by alpha-hydroxylation) and glutamate (presumably by beta-oxidation) from lignoceric acid was recovered. The role of the acidic amino acids in the metabolic conversion of lignoceric acid in brain appears to be their conversion to the corresponding alpha-keto acids and then incorporation into the TCA cycle. Glucose 6-phosphate is also likely to be involved in the TCA cycle through the Emden-Meyerhof pathway. Inorganic phosphate and AMP seemingly are used to produce ATP. However, the addition of up to 20 mM ATP alone did not replace the heat-stable factor.

Amino Acids↗