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Biomedical subjects

S Kato

Publications and source records attributed to S Kato.

At least 973 records · Page 54Linked to original sources
PubMed1993

Human glyoxalase I. cDNA cloning, expression, and sequence similarity to glyoxalase I from Pseudomonas putida.

Glyoxalase I (EC 4.4.1.5) catalyzes the transformation of methylglyoxal and glutathione to S-lactoylglutathione. We have isolated human cDNA clones encoding glyoxalase I from a phorbol myristate acetate-treated U937 cDNA library. This cDNA encodes a protein of 184 amino acids with a calculated M(r) of 20,719. The amino acid composition calculated from the deduced amino acid sequence agreed with that reported for glyoxalase I purified from human erythrocytes. The Escherichia coli cells carrying the expression vector of this cDNA acquired methylglyoxal resistance and the cell lysate showed the high activity of glyoxalase I. The amino acid sequence of human glyoxalase I exhibited 57% identity with Pseudomonas putida glyoxalase I at the C-terminal two-thirds, suggesting that the two enzymes may have originated from a common ancestor.

Amino Acid Sequence↗
PubMed1993

Recombinant f1 phage particles can transfect monkey COS-7 cells by DEAE dextran method.

Recombinant f1 phage particles containing cDNA of the human urokinase type-plasminogen activator (u-PA) under the control of the simian virus 40 (SV40) early promoter were used for transfection of monkey COS-7 cells using a DEAE dextran method. The fibrinolytic activity of u-PA was detected in the culture medium of the 10(5) cells transfected with the phage particles containing single-stranded (ss) DNA of more than 0.2 ng. This finding will lead us to develop a simple and efficient method for expression cloning using mammalian cells.

Animals↗
PubMed1993

Thyroid hormone affects the gene expression of retinoid X receptors in the adult rat.

Gene expression of three nuclear retinoid X receptors (RXR alpha, beta and gamma) was examined by Northern blot analysis in various rat tissues. The RXR alpha mRNA (5.5 kb) was detected in most tissues and particularly expressed at a high level in the liver. The RXR beta transcripts (2.4 and 3.0 kb) were expressed ubiquitously, and particularly at high levels in the brain and testis. In the liver, heart, kidney and lung, the RXR gamma mRNA (2.0 kb) was specifically detected. Furthermore, we examined the effect of retinoid, vitamin D and thyroid hormone status on the gene expression of RXR alpha, beta and gamma. Though retinoid and vitamin D did not affect the mRNA levels of three RXRs, the mRNA levels of two genes were controlled by thyroid hormone. Namely, positive (RXR beta) and negative (RXR gamma) regulations by thyroid hormone were observed with no effect on the gene expression of RXR alpha. These results suggest that thyroid hormone might affect the signal transduction of retinoid, vitamin D and thyroid hormone by changing RXR levels.

Animals↗
PubMed1993

Allele-specific activation of the c-myc gene in an atypical Burkitt's lymphoma carrying the t(2;8) chromosomal translocation 250 kb downstream from c-myc.

The genetic structure and regulation of the c-myc gene was comprehensively studied for the first time in Burkitt's lymphoma with t(2;8) translocation. In a Burkitt's lymphoma cell line, KOBK101, the immunoglobulin kappa-encoding gene on chromosome 2, accompanied by its enhancer, was translocated to the pvt-1 locus located about 250 kb downstream from c-myc on chromosome 8. Only the c-myc allele on the translocated chromosome carried aberrant SalI and KpnI sites in the first intron, so the two c-myc alleles and their transcripts were analyzed separately. The c-myc allele on the untranslocated chromosome conserved the normal c-myc sequence and was transcriptionally silent. In contrast, the c-myc allele on the translocated chromosome was actively transcribed at three- to fivefold higher levels, as compared with non-malignant B-cell lines. Additionally, it carried predominant multiple mutations consisting of 64 nucleotide substitutions, three short deletions, and a one-base insertion, most of which clustered in the first exon and intron. The 24-base deletion in the first intron completely overlapped the binding site of a putative negative transcriptional factor of the 138-kDa phosphoprotein, MIF. Thus, the multiple mutations and the deregulated, allele-specific expression of c-myc were associated with the chromosomal translocation in cis. Together activation by the long-distance immunoglobulin kappa enhancer, and the alleviation of negative regulation by the mutations, seemed to cause the allele-specific activation of c-myc.

Alleles↗
PubMed1993

Anti-tumor activity of ceramides and glycosphingolipids in a murine tumor system.

The anti-tumor activity of 7 sphingolipids, 2 ceramides and 5 glycosphingolipids against the syngeneic murine ascitic tumors MH134 and MM102 in C3H mice was examined. Five of these compounds showed anti-tumor activity against the tumors, ceramide type-IV (Cer-IV) having the highest activity without cytotoxic or cytostatic activity. These results indicate that the fatty acid in ceramide and sugar chains binding to it affect the anti-tumor activity in vivo. The anti-tumor activity of Cer-IV depended on the time of treatment. Mice treated with Cer-IV one day after tumor implantation showed the highest rate of survival. The cured mice were resistant to rechallenge with the same tumor (MH134-->MH134, MM102-->MM102) but not with a heterologous tumor (MH134-->X5563, MM102-->X5563), indicating that the effect of Cer-IV may be due to in vivo induction of specific immunity. Studies with various antibodies demonstrated that the anti-tumor effect of Cer-IV was inhibited by all the antibodies tested (L3T4, Lyt-2, and Thy-1,2 T cells, macrophages, and TNF alpha) in the induction phase (before Cer-IV administration) and by the antibodies of L3T4 and TNF alpha in the effector phase (after Cer-IV administration). Therefore, the anti-tumor effect of Cer-IV in this system depended on the host immune response rather than on its direct cytotoxic and/or cytostatic action.

Animals↗
PubMed1993

A point mutation found in the WT1 gene in a sporadic Wilms' tumor without genitourinary abnormalities is identical with the most frequent point mutation in Denys-Drash syndrome.

We have analyzed exon 9 of the WT1 gene of 18 non-familial/sporadic unilateral Wilms' tumors (WTs) from Japanese patients, by the polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) method. After screening these WTs, a nucleotide alternation, which was present on both alleles, was found in only one case. Furthermore, PCR-SSCP analysis of the constitutional DNA revealed that this patient carried the mutation on only one allele in the germline. Sequence analysis showed that the tumor carried a point mutation (C-1180 to T-1180) in WT1 exon 9 of both alleles, resulting in an Arg-394 to Trp-394 amino acid substitution within the third zinc finger domain of the WT1 product. Interestingly, this mutation is identical with the most frequent point mutation associated with the Denys-Drash syndrome. However, the classical triad of Denys-Drash syndrome does not apply to this patient. This is in the first report of the point mutation in the zinc finger domain of both WT1 alleles in a sporadic unilateral WT without genitourinary abnormalities, and the mutation suggests that some sporadic WTs carry the Denys-Drash WT1 mutations.

Base Sequence↗
PubMed1993

Capacity of rete testicular and cauda epididymal boar spermatozoa to undergo the acrosome reaction and subsequent fusion with egg plasma membrane.

The capacity to undergo the acrosome reaction and subsequent fusion with egg plasma membrane was examined in rete testicular and cauda epididymal spermatozoa from boars. Sperm penetration assay using zona-free hamster eggs demonstrated that the penetration rates for rete testicular spermatozoa preincubated for induction of the acrosome reaction for 2 and 3 h were 55% and 97%, respectively. However, most of the eggs (93%) were penetrated with polyspermy by cauda epididymal cells preincubated for 2 h. Results obtained by the triple-stain technique revealed the percentages of acrosome-reacted spermatozoa in the rete testicular and cauda epididymal samples preincubated for 3 h to be 61% and 74%, respectively. These results indicate that many rete testicular spermatozoa possess the capacity to undergo the acrosome reaction and subsequent fusion with egg plasma membrane in vitro, which appears to be completely established only after sperm transit through at least the proximal part of the epididymis.

Acrosome↗
PubMed1993

Molecular cloning of a novel isotype of Mg(2+)-dependent protein phosphatase beta (type 2C beta) enriched in brain and heart.

Two complementary DNA (cDNA) clones (pTK-1 and -2) encoding two distinct isotypes of mouse Mg(2+)-dependent protein phosphatase beta (MPP beta-1 and -2, respectively) were isolated from a melanocyte cDNA library. Although mouse pTK-1 is orthologous to the rat cDNA (JW5) reported previously [Wenk, J., Trompeter, H.I., Pettrich, K.G., Cohen, P.T.W., Campbell, D.G., and Mieskes, G. (1992) FEBS Lett. 297, 135-138], pTK-2 is a novel cDNA clone. It was strongly suggested that the pTK-1 and -2 cDNAs are splicing variants of a single pre-mRNA. The difference in the amino acid sequences between MPP beta-1 and -2 was observed only at the carboxy-terminal regions. Both the recombinant MPP beta-1 and -2 expressed in Escherichia coli cells were immunoreactive to an anti-MPP beta antibody and exhibited Mg(2+)-dependent and okadaic acid-insensitive protein phosphatase activities with similar substrate specificities. Although the mRNA of MPP beta-1 was expressed ubiquitously in various mouse tissues, that of MPP beta-2 was expressed exclusively in brain and heart. These results suggest the difference in the physiological roles of these two enzyme isotypes.

Amino Acid Sequence↗
PubMed1993

Superior mesenteric arteriovenous fistula: report of a case and review of the literature.

Iatrogenic arteriovenous fistula of the superior mesenteric vessels is rare, with only 22 cases being documented. We report herein a case of a 63-year-old man with an iatrogenic arteriovenous fistula which developed after a small bowel resection for intestinal tuberculosis. The patient was admitted to our hospital for a gastric ulcer, at which time an ultrasonogram demonstrated cystic dilatation of the superior mesenteric vein, proving to be an arteriovenous fistula of the mesenteric vessels. An angiogram of the superior mesenteric vessels subsequently confirmed this diagnosis and resection of the fistula was performed, followed by an uneventful recovery. Iatrogenic mesenteric arteriovenous fistula with no presenting symptoms, as in our case, is uncommon and surgery performed before the development of associated portal hypertension should achieve good results. A review of the literature follows the report of this case.

Arteriovenous Fistula↗
PubMed1993

Mechanism by which histamine increases gastric mucosal blood flow in the rat. Role of luminal H+.

The mechanism by which histamine increases gastric mucosal blood flow (GMBF) was investigated in the anesthetized rat. The experiment was performed in the presence of tripelennamine, an H1 antagonist, to focus on the relationship between acid secretion (H2-receptor-mediated response) and GMBF. The stomach was mounted on a Lucite chamber, perfused with saline, and GMBF was measured by laser Doppler flowmetry simultaneously with acid secretion. Under these conditions, histamine at the submaximal dose significantly increased GMBF as well as acid secretion, and this increase of GMBF was completely blocked when acid secretion was inhibited by cimetidine or omeprazole. The elevation of GMBF caused by histamine was also significantly attenuated when luminal H+ was removed by intraluminal perfusion with NaHCO3 or glycine. Glycine by itself did not affect the increase of acid secretion induced by histamine and the increase of GMBF caused by isoproterenol, yet significantly inhibited the GMBF response induced by pentagastrin. Intraluminal perfusion with HCl also produced an increase of GMBF in a concentration-related manner, even in the presence of omeprazole during histamine infusion. Pretreatment of the animals with indomethacin significantly blocked the GMBF responses induced by either histamine or luminal HCl. These results suggest that the increase of GMBF during acid secretion induced by histamine may be caused by luminal H+ and involve endogenous prostaglandins in its mechanism.

Animals↗
PubMed1993

Influence of HCV infection and its subtypes on clinical course of alcoholic liver disease.

Since the assay of HCV antibody has been developed, it became clear that HCV is involved not only in patients with non-A non-B hepatitis but also in some alcoholic patients. The aim of this study is to examine the prevalence of HCV in chronic alcoholics and to elucidate the influence of HCV and its subtypes on pathogenesis and clinical feature of alcoholic liver disease. To that effect, sera from 100 alcoholics were tested for antibody against C100 of HCV by ELISA and for HCV RNA by reverse transcriptation and the PCR method. The incidence of HCV Ab/RNA was 0%/17% in patients with non specific reactive hepatitis, 0%/0% in fatty liver, 17%/17% in alcoholic hepatitis, 50%/73% in chronic hepatitis, 15%/18% in liver fibrosis and 19%/31% in liver cirrhosis. HCV Ab and RNA were positive in 21% and 31% of alcoholics, respectively. Subtypes of HCV were identified by dot blot hybridization method. Type K1, K2a and K2b were detected in 68%, 25% and 7% of 28 patients with positive HCV RNA, respectively. Type PT was not detected. In addition, serum transaminase activities were evaluated after 4 weeks abstinence. The incidence of normalization of the enzyme activity was lower in patients with positive HCV RNA than that with negative HCV RNA. Furthermore, when it was estimated in relation to HCV subtypes, the incidence of normalization in patients with type K1 was lower than that with type K2. In conclusion, the prevalence of HCV infection in alcoholic patients was much greater than general population.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Effect of linoleic acid hydroperoxide on production of matrix metalloproteinases by human aortic endothelial and smooth muscle cells.

The effect of linoleic acid hydroperoxide on the production of proforms of matrix metalloproteinase-1, -2, and -3 (proMMP-1, -2, and -3) in cultured human arterial endothelial and smooth muscle cells was investigated. Upon cultivation of the endothelial cells in the absence of the hydroperoxide, only proMMP-1 was detected, and its amount was increased by cultivation with the hydroperoxide. In the cultures of the intimal smooth muscle cells in the absence of the hydroperoxide, a large amount of proMMP-2 and small amounts of proMMP-1 and -3 were detected, and the hydroperoxide treatment increased remarkably the amounts of proMMP-1 and -3, but rather decreased the amount of proMMP-2. In the cultures of the medial smooth muscle cells, the same tendency was observed. However, the amounts of these proenzymes found in the intimal smooth muscle cells exceeded those found in the medial smooth muscle cells, both in the absence and in the presence of the hydroperoxide. Possible involvement of these phenomena in atherogenesis was discussed.

Aorta, Thoracic↗
PubMed1993

Involvement of the frontotemporal lobe and limbic system in amyotrophic lateral sclerosis: as assessed by serial computed tomography and magnetic resonance imaging.

The present paper concerns serial examinations of computed tomography (CT) and magnetic resonance imaging (MRI) in 22 patients with sporadic amyotrophic lateral sclerosis (ALS). Supranuclear ophthalmoplegia developed in 13 and dementia in 3 patients. The investigations showed gradually progressive atrophy, first in the frontal and anterior temporal lobes then in the precentral gyrus, and later in the postcentral gyrus, anterior part of the cingulate gyrus, corpus callosum and brain stem tegmentum. MRI revealed high intensity signals on T2-weighted images in the precentral and adjacent gyri, frontotemporal white matter and pyramidal tract as well as rarely in the globus pallidus and thalamus. These neuroradiological changes were not related to the duration of the clinical course or to the degree of the motor impairment. These alterations may play a critical role in the supranuclear ophthalmoplegia seen in ALS patients. The dementia of ALS probably reflects involvement of both the frontotemporal lobes and limbic system.

Adult↗
PubMed1993

Suppressive effect of GABA on insulin secretion from the pancreatic beta-cells in the rat.

In order to investigate a possible role of GABA in the regulation of insulin secretion, we have studied the effect of GABA on insulin secretion from the isolated perfused rat pancreas in vitro and on the changes in the cytoplasmic Ca2+ of Beta-cells from the isolated rat islets. When glucose is present, GABA caused a dose dependent inhibition of the first phase of arginine-induced insulin secretion during the range of 10-1000 microM, but GABA did not affect arginine-induced insulin secretion in the absence of glucose. GABA inhibited not only the first phase but also the second phase of glucose-induced insulin secretion. A GABAB-receptor agonist, baclofen, also inhibited both phases of insulin secretion induced by 16.7 mM glucose. Furthermore, GABA inhibited the rise in cytoplasmic Ca2+ of Beta-cells in response to 16.7 mM glucose. These studies indicate that GABA decreases Beta cell secretory activity mainly in response to glucose. These inhibitory effects of GABA on insulin secretion may be mediated through GABAB-receptor and the inhibition of the rise in cytoplasmic Ca2+.

Animals↗
PubMed1993

Selective impairment of the cytoplasmic Ca2+ response to glucose in pancreatic beta cells of streptozocin-induced non-insulin-dependent diabetic rats.

Pancreatic islets from the streptozocin-induced non-insulin-dependent diabetes mellitus (NIDDM) rat model showed a diminished insulin response to 16.7 mmol/L glucose, but the insulin response to arginine remained intact. To evaluate the importance of intracellular calcium concentration ([Ca2+]i) in the diminished insulin response to glucose, the [Ca2+]i of pancreatic beta cells was investigated using fura-2. Glucose produced heterogeneous responses of [Ca2+]i, which were in beta-cell clusters of both the control and NIDDM groups. Many cells showed initial slight decreases of [Ca2+]i, which were followed by gradual and large increments of [Ca2+]i after glucose stimulation of beta cells in the control group. On the other hand, the increase of [Ca2+]i in response to glucose was markedly diminished in beta cells of the NIDDM group compared with controls. The average lag time to [Ca2+]i elevation of beta cells in the NIDDM group was significantly longer than that of the control group. Arginine produced marked increases of [Ca2+]i, in contrast to the effect of glucose stimulation in the NIDDM group. These results suggest that the diminished and delayed [Ca2+]i increases in beta cells of NIDDM rats in response to glucose stimulation are responsible for the selectively impaired insulin response to glucose in the rat model of NIDDM.

Animals↗
PubMed1993

Cystine/glutamate antiporter expression in retinal Müller glial cells: implications for DL-alpha-aminoadipate toxicity.

A cytotoxicity of glutamate or related amino acids (10 mM) mediated by a cystine/glutamate antiporter (system Xc) has recently been demonstrated in N18 neuroblastoma-rat retina hybrid (N18RE105) cells and C6 glioma cells. The antiporter usually transports glutamate outside and cystine inside, thereby maintaining cellular concentrations of glutathione. High concentrations of glutamate inhibit cystine uptake and lead to depletion of cellular levels of glutathione. Among related amino acids, DL-alpha-aminoadipic acid (DL-alpha-AAA), which is well known as a selective gliotoxin in the retina, is also toxic to these cells. However, this does not explain why DL-alpha-AAA acts gliospecifically on the retina. To answer this question we first examined the effects of DL-alpha-AAA on the [35S]cystine uptake with parental N18 neuroblastoma cells and rat retina of the hybrid cells. DL-alpha-AAA showed a competitive inhibition of [35S]cystine uptake in the rat retina but not in the N18 cells. Such a competitive inhibition of cystine uptake by DL-alpha-AAA could also be seen in the carp retina. The cystine uptake with carp retina was mainly Na(+)-independent and Cl(-)-dependent as already described as a characteristic ion dependency of the Xc antiporter. We next examined the effects of exogenous cystine on the glutamate release from the retina. Cystine (1 mM) actually induced a glutamate release approximately twice that of the control. Furthermore, the glutamate release induced by cystine was also Na(+)-independent and Cl(-)-dependent, and was blocked by DL-alpha-AAA. An autoradiogram of [35S]cystine uptake in the carp retina showed typical radial glial Müller cells. A large incorporation of [35S]cystine into retinal glutathione fraction was detected by a high pressure liquid chromatography method during a 1-4-h incubation. A significant or large decrease of retinal levels of glutathione was observed one day ater an intravitreal injection of 8 mumol DL-alpha-AAA or L-alpha-AAA, respectively. Buthionine sulfoximine (2.5 mumol), a specific inhibitor of glutathione synthesis, induced a large decrease of retinal levels of glutathione and a loss of electroretinographic b-wave 20-30 h after treatment. Taken together, our present data with rat and carp retinas strongly indicate that the expression of cystine/glutamate antiporter is enriched in the retina, particularly in the glial Müller cells which have a rapid turnover pool for glutathione. The gliotoxin DL-alpha-AAA inhibits cystine uptake through this antiporter on the glial cells and elicits reduction of cellular levels of glutathione.(ABSTRACT TRUNCATED AT 400 WORDS)

2-Aminoadipic Acid↗
PubMed1993

Condition for the appearance of the metastable P beta' phase in fully hydrated phosphatidylcholines as studied by small-angle x-ray diffraction.

In the ripple phase of fully hydrated multilamellar vesicles of dipalmitoylphosphatidylcholine (DPPC), two kinds of small-angle x-ray diffraction profiles are observed on cooling through the main transition. One is a seemingly normal profile similar to that observed on heating and the other is the superposition of the diffraction profiles for the primary (normal) and the secondary ripple structures. We found that the profile obtained depended on the cooling rate. Increasing the cooling rate from 0.1 degrees C/min to 1 degrees C/min caused the peaks originating from the secondary ripple structure to diminish. After a cooling scan at 43 degrees C/min, the profile became similar to that of the normal ripple structure, although a trace of the secondary ripple structure remains. The results are interpreted in terms of the rise and fall of three-dimensional correlated domains composed of both primary and secondary ripple structures. At slow cooling rates, correlated domains of both kinds of ripple structures develop. As the cooling rate is increased, the domain of the primary ripple structure remains correlated, while that of the secondary ripple structure becomes less correlated. In addition, the multipeak profile appears even at rapid cooling rates, if the final low temperature lies just below the Tm for the main transition. This results suggests that formation of the correlated domains of the secondary ripple structure requires a certain time interval during which the DPPC vesicles experience the temperature just below the main transition. The secondary ripple structure takes place in phosphatidylcholines having more than 15 carbons in each hydrocarbon chain upon cooling through the main transition.

1,2-Dipalmitoylphosphatidylcholine↗