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Biomedical subjects

S Kato

Publications and source records attributed to S Kato.

At least 19 recordsLinked to original sources
PubMed1992

Cytochrome P450IIE1 genetic polymorphisms, racial variation, and lung cancer risk.

Cytochrome P450IIE1 is responsible for the activation of carcinogenic N-nitrosamines, benzene, urethane, and other low-molecular-weight compounds. Restriction fragment length polymorphisms (PstI and RsaI restriction enzymes) have been identified in the cytochrome P450IIE1 transcription regulatory region that may affect expression. This study describes the PstI and RsaI polymorphisms in different racial populations and in a case-control study of lung cancer. The allelic frequencies were markedly different in Japanese, African-Americans, and Caucasians: the PstI rare allele was present at a frequency of 2% in Caucasians, 5% in African-Americans, and 24% in Japanese (P < 0.05). For the RsaI rare allele, frequencies were 2% in Caucasians, 2% in African-Americans, and 27% in Japanese (P < 0.05). The assay was also applied to 128 individuals enrolled in a case-control study of lung cancer. Although limited in statistical power, the data indicate no evidence for an association in the aggregate of cytochrome P450IIE1 PstI [for which the odds ratio was 0.7 (95% confidence interval (C.I.) = 0.2-2.8)] or RsaI [for which the odds ratio was 0.9 (95% C.I. = 0.2-5.4)] restriction fragment length polymorphisms with lung cancer in this U.S. population. When analyzed by race, the lung cancer odds ratio for the PstI mutant allele in African-Americans was 0.19 (95% C.I. = 0.03-1.38), and in Caucasians it was 4.13 (95% C.I. = 0.34-48.8). For the RsaI mutant allele, the odds ratios were 0.20 (95% C.I. = 0.02-2.43) and 4.28 (95% C.I. = 0.35-50.6), respectively. The ethnic differences of these restriction fragment length polymorphisms might be related to genetic susceptibilities for lung cancer among Caucasians and for gastric or esophageal cancer among Japanese.

Alleles↗
PubMed1992

Identification of the binding site of 55kDa tumor necrosis factor receptor by synthetic peptides.

We have synthesized a series of peptides, which cover almost the whole range of the N-terminal extracellular domain of human 55kDa TNF receptor (55kDa TNF-R). The peptides were examined for the binding activity to TNF by solid phase binding assay and for the inhibition of TNF cytotoxicity to mouse L-M cells. The peptide 159-178 exhibited remarkably higher binding activity to TNF than other peptides did. The specificity of the TNF binding to the peptides was confirmed by their inability to bind other cytokines. The peptide 159-178 also inhibited TNF cytotoxicity. These results indicate that the specific binding site of 55kDa TNF-R to TNF might reside within the peptide segment of amino acid numbers 159 to 178 in the N-terminal extracellular domain.

Amino Acid Sequence↗
PubMed1992

Tissue-specific response of estrogen receptor gene expression to estrogen in chick.

We have developed a sensitive assay system by RT (reverse transcription)-PCR(polymerase chain reaction) to detect the low level of chicken estrogen receptor (cER) transcript. Using this system, the differential expression of cER gene in chick tissues was observed. Moreover, we found that the oviduct cER transcript levels in chick was not affected, albeit the remarkable growth of this tissue, by exogenous estrogen. In contrast, estrogen enhanced the hepatic cER transcript level several folds. Thus, the present study clearly showed a novel tissue-specific response of cER gene expression to estrogen in chick.

Animals↗
PubMed1992

Effects of poly(L-lysine) on the structural and thermotropic properties of dipalmitoylphosphatidylglycerol bilayers.

The effects of poly(L-lysine) on the structural and thermotropic properties of dipalmitoylphosphatidylglycerol (DPPG) bilayers were studied with differential scanning calorimetry (DSC), X-ray diffraction and freeze-fracture electron microscopy. For thermal behavior, in the DPPG/poly(L-lysine) system the main transition temperature rises to 45.7 degrees C and the pretransition disappears in opposition to pure DPPG vesicles. An additional transition appears approximately at 36 degrees C for the DPPG/poly(L-lysine) system after incubation at 4 degrees C for two months. The incubated sample gives a X-ray diffraction pattern having several additional reflections in the range of 0.2-0.9 nm at 15 degrees C. These results suggest that even in the presence of poly(L-lysine) the DPPG bilayers form the subgel (Lc) phase after the long incubation at a low temperature. The X-ray diffraction measurements indicate that the structure of the Lc phase for DPPG/poly(L-lysine) system is different from that of pure DPPG bilayers. On the other hand, in the gel (L beta') phase, the wide-angle X-ray diffraction pattern suggests that the presence of poly(L-lysine) hardly affects the packing of hydrocarbon chains in the DPPG bilayers. The small-angle X-ray diffraction and freeze-fracture electron microscopy exhibit that the DPPG/poly(L-lysine) system forms a tightly packed multilamellar structure in which the poly(L-lysine) is intercalated between the subsequent DPPG bilayers.

Calorimetry, Differential Scanning↗
PubMed1992

Effect of retinoid status on alpha, beta and gamma retinoic acid receptor mRNA levels in various rat tissues.

We have investigated the effects of retinoids, vitamin D and thyroid hormone on the levels of retinoic acid receptor (RAR)alpha, RAR beta and RAR gamma mRNAs in intact animals. Although vitamin A deficiency caused no significant changes in the levels of RAR alpha and RAR gamma mRNAs, the level of RAR beta transcripts was greatly decreased in various tissues of vitamin A-deficient rats, but was restored rapidly to a normal level after administration of retinoic acid. Retinol also restored the RAR beta mRNA level, but the magnitude and kinetics of the induction differed from those by retinoic acid. The use of specific inhibitors demonstrated that this autoregulation of RAR beta gene expression in vivo occurred at the transcriptional level. In addition, from these results it was postulated that the maintenance of the normal RAR beta mRNA levels seemed to require a threshold serum retinol concentration (about 25 micrograms/dl). Moreover, we found that administration of retinol and retinoic acid to normal rats caused the overexpression of RAR beta transcripts (2-15-fold) when compared with the control levels of RAR beta mRNA, although the levels of RAR alpha and RAR gamma mRNAs were not affected. Vitamin D and thyroid hormone did not modulate the levels of RAR transcripts. These findings clearly indicate the specific ligand regulation of RAR beta gene expression in intact animals. The altered levels of RAR beta according to retinoid status may affect retinoid-inducible gene expression.

Animals↗
PubMed1992

Identification of an amino acid residue involved in the substrate-binding site of rat liver uricase by site-directed mutagenesis.

Computer analysis has shown that a conserved amino acid sequence (Leu 160 to Lys 164) of rat liver uricase is also present in other enzymes with purine substrates. The significances of the amino acids in this sequence were studied by site-directed mutagenesis. Replacement of Lys 164 by Glu or Ile resulted in loss of uricase activity and decrease in binding of the competitive inhibitor xanthine. The far ultraviolet circular dichroic spectra of the mutant uricases were identical to that of the wild type protein, indicating that the replacement of Lys 164 by other amino acids did not result in serious modification of the conformation of uricase. These findings suggest that this amino acid is involved in the substrate-binding site of the enzyme.

Amino Acid Sequence↗
PubMed1992

Modulation of expression of multidrug resistance gene (mdr-1) by adriamycin.

The acquired resistance to various drugs in cancer is mediated by P-glycoprotein (P-gp) which is encoded by the mdr-1 gene. An increased level of mdr-1/P-gp was demonstrated after chemotherapy administered to treat cancer in humans. To clarify the direct effect of anticancer drugs on mdr-1/P-gp expression, we investigated the change in transport of adriamycin (ADR), and the expression of the mdr-1 gene and P-gp in an ADR-treated, multidrug-resistant leukemic cell line (K562/ADR500). The addition of ADR induced the over-expression of mdr-1/P-gp, which led to a transient decrease in the intracellular accumulation of ADR although the difference was not statistically significant. A maximal effect was observed after 4 h incubation, returning to the baseline level after further incubation for 12-24 h. The phosphorylation of P-gp was inversely correlated with the levels of P-gp. These observations suggest that ADR itself modulates both the expression and function of P-gp. Determination of the optimal schedule for administering adriamycin is essential to achieving the optimal effect in treating cancer.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

5-HT3 receptor antagonist effects of DAT-582, (R) enantiomer of AS-5370.

The serotonin 5-HT3 receptor antagonist effects of DAT-582, the (R) enantiomer of AS-5370 ((+/-)-N-[1-methyl-4-(3-methyl-benzyl)hexahydro-1H-1,4-diazepin-6- yl]-1H- indazole-3-carboxamide dihydrochloride), and its antipode were compared with those of AS-5370 and existing 5-HT3 receptor antagonists. In anesthetized rats, DAT-582 antagonized 2-methyl-5-HT-induced bradycardia with an ED50 value of 0.25 microgram/kg i.v., whereas the (S) enantiomer was without effect even at 1000 micrograms/kg i.v. In antagonizing the bradycardia, DAT-582 was as potent as granisetron, slightly more potent than AS-5370, and 2, 5 and 18 times more potent than ondansetron, ICS 205-903 and renzapride, respectively, although it was less potent than zacopride. DAT-582 inhibited cisplatin (10 mg/kg i.v.)-induced emesis in ferrets with an ED50 value of 3.2 micrograms/kg i.v. twice. The antiemetic activity of DAT-582 was more potent than that of the existing 5-HT3 receptor antagonists examined, except zacopride. In contrast, the (S) enantiomer had little effect at 1000 micrograms/kg i.v. twice. In isolated guinea-pig ileum, DAT-582 inhibited 5-HT-induced contractions with an IC50 value of 91 nM, whereas the (S) enantiomer hardly inhibited them even at 1000 nM. These results suggest that DAT-582, the (R) enantiomer of AS-5370, potently and selectively blocks 5-HT3 receptors.

Animals↗
PubMed1992

Involvement of a receptor for neurite outgrowth factor (NOFR) in cerebellar neurogenesis.

A receptor for neurite outgrowth factor (82 kDa membrane protein, NOFR) was detected in the developing chick cerebellum by immuno- and ligand blots. In immunohistochemical study, NOFR was maximally expressed in the external granular layer of cerebellum at embryonic day 10-12 and gradually decreased until embryonic day 18. Neurite outgrowth and cell migration induced by NOF from cerebellar explants were completely suppressed by the addition of anti-NOFR IgG. These results suggest that NOFR plays an important role in the cerebellar neurogenesis.

Animals↗
PubMed1992

Alteration of rat liver proteoglycans during regeneration.

Sepharose CL-6B column chromatography of crude extracts from the slices of regenerating rat livers after partial hepatectomy and sham-operated controls labeled with [35S]sulfuric acid revealed an enhancement of [35S]sulfate incorporation into proteoglycan fractions during regeneration. The 35S-labeled proteoglycans contained heparan sulfate (more than 80% of the total) and chondroitin/dermatan sulfate. The 35S-incorporation into both glycosaminoglycans increased to maxima 3-5 days after partial hepatectomy and decreased thereafter toward the respective control levels. When [35S]sulfuric acid was replaced by [3H]glucosamine, similar results were obtained. These results suggest that the maximal stimulation of proteoglycan synthesis in regenerating rat liver follows the maximal mitosis of hepatic cells 1-2 days after partial hepatectomy. The 35S-labeled proteoglycans from regenerating liver 3 days after partial hepatectomy and control were analyzed further. They were similar in chromatographic behavior on a gel filtration or an anion-exchange column and in glycosaminoglycan composition. Their glycosaminoglycans were indistinguishable in electrophoretic mobility. However, these proteoglycans were slightly but significantly different in their affinity to octyl-Sepharose and in the molecular-weight distribution of their glycosaminoglycans.

Animals↗
PubMed1992

A far upstream estrogen response element of the ovalbumin gene contains several half-palindromic 5'-TGACC-3' motifs acting synergistically.

We have identified an estrogen-responsive enhancer element (DH3 ERE) in the estrogen-induced DNAase I-hypersensitive region III of the chicken ovalbumin gene, which is located approximately 3.3 kb upstream from the mRNA start site and does not contain palindromic ERE. Four TGACC half-palindromic motifs, separated from each other by more than 100 bp, are responsible for conferring estrogen inducibility either to the proximal ovalbumin gene promoter or to heterologous promoters. Thus, widely spaced half-palindromic ERE motifs can act synergistically. Each half-palindromic motif was shown to bind the estrogen receptor (ER) with a low efficiency in vitro. However, two widely spaced half-palindromic motifs bound the ER cooperatively, much more efficiently than expected from binding to isolated half-ERE motifs. The ovalbumin promoter half-palindromic ERE motif located close to the TATA box was required for the activity of the distal DH3 ERE, but could be replaced by the binding sites of other transactivators.

Animals↗
PubMed1992

Ultrastructural and immunohistochemical studies on ballooned cortical neurons in Creutzfeldt-Jakob disease: expression of alpha B-crystallin, ubiquitin and stress-response protein 27.

This report concerns ultrastructural and immunohistochemical studies on ballooned neurons of ten patients with Creutzfeldt-Jakob disease (CJD). While abundant ballooned neurons and severe white matter degeneration was seen in six Japanese cases, only occasional ballooned neurons and no white matter degeneration was observed in four cases from the files of Montefiore Medical Center. Ultrastructurally, the ballooned neurons contained granule-coated fibrils of 25 to 40 nm in width and 10-nm neurofilaments. The immunohistochemical studies revealed that most ballooned neurons expressed alpha B-crystallin, with deposits of reaction products observed in the cytoplasm. A similar intracellular staining pattern was also seen with the antibody to phosphorylated neurofilament proteins (pNFP). Although the proportion of stained ballooned neurons was less, a positive reaction was also observed with antibodies against ubiquitin, stress-response protein 27 (srp 27) and synaptophysin, but not with an antibody to srp 72. Our findings suggest that expression of pNFP and synaptophysin by ballooned neurons may reflect axonal impairment and that the presence of alpha B-crystallin, srp 27 and ubiquitin may be related to the degenerative processes that neurons undergo in CJD.

Aged↗
PubMed1992

Immunohistochemical studies on the new type of astrocytic inclusions identified in a patient with brain malformation.

Immunohistochemical studies were carried out on the new type of cerebral cortical astrocytic inclusions recently discovered in a 20-year-old patient with maldeveloped brain and micropolygyria. The inclusions appeared as eosinophilic structures (hematoxylin and eosin stain) and did not exhibit argyrophilia (modified Bielschowsky method). The inclusions were strongly stained by the antibody against S-100 protein (S 100) and to a lesser extent by the antibody to microtubule-associated protein 1B (MAP 1B). In contrast to Rosenthal fibers, the astrocytic inclusions did not react with antibodies to alpha B-crystallin, glial fibrillary acidic protein and ubiquitin. No positive reactions were obtained with antibodies against heat-shock protein 27 (HSP 27), HSP 72, actin, vimentin, desmin, cytokeratin, myelin basic protein, beta-tubulin, MAP 2, tau protein, paired helical filament, phosphorylated neurofilament protein (NFP), nonphosphorylated NFP, synaptophysin, cathepsin D, alpha 1-antichymotrypsin, alpha 1-antitrypsin and basic fibroblast growth factor. By immunoelectron microscopy, the products of the reaction with the anti-S 100 antibody appeared as heterogeneous granular deposits and with the antibody to MAP 1B they were randomly scattered throughout the astrocytic inclusions. Our results demonstrate that the immunohistochemical profile of the recently described inclusions differs from that of Rosenthal fibers. Whether the novel inclusions are involved in congenital astrocyte dysfunction and cerebral malformation remains to be established.

Adult↗
PubMed1992

Stress-response (heat-shock) protein 72 expression in tumors of the central nervous system: an immunohistochemical investigation.

This report deals with the expression of stress-response (heat-shock) protein 72 (srp 72) in a series of 95 primary human brain tumors and 21 carcinoma metastases to the central nervous system (CNS). Immunohistochemical procedures were employed; cells of the human cervical cancer line HeLa S3 were used as positive controls. The protein was detected in 14/22 meningiomas and in 6/13 glioblastomas. Tumor cells expressing srp 72 were also found in 4/17 astrocytomas, 2/9 pituitary tumors, 2/14 primitive neuroectodermal tumors and 1/10 medulloblastomas. Whereas the majority (8/10) of the breast carcinoma metastases had tumor cells that expressed srp 72, only 2/11 lung tumor metastases were positively stained. These results document srp 72 expression by a variety of primary and metastatic tumors of the CNS.

Antibodies, Monoclonal↗
PubMed1992

Increased iron content in the putamen of patients with striatonigral degeneration.

We measured the total content of iron, copper, zinc and manganese in the putamen of four patients with striatonigral degeneration (SND) and age- and gender-matched normal controls. The iron content in the SND patients was five times greater than in the controls. Electron microscopic histochemistry revealed the iron reaction products in the pigments showing a triphasic pattern of coarse, electron-dense globules, fine granular and fibrillary materials, and lamellated structures. These findings suggest that increased iron deposition may be related to pigment formation in the putamen of SND.

Aged↗
PubMed1992

Ultrastructural identification of neurofibrillary tangles in the spinal cords in Guamanian amyotrophic lateral sclerosis and parkinsonism-dementia complex on Guam.

The immunohistochemical and ultrastructural characteristics of spinal cord neurofibrillary tangles (NFTs) were examined in Guamanian amyotrophic lateral sclerosis and in parkinisonism-dementia complex on Guam. The spinal cord NFTs reacted with antibodies to tau protein (tau-2), ubiquitin and paired helical filaments (PHFs). Ultrastructurally, the components of the NFTs were seen as randomly arranged fibrils which were often associated with osmiophilic granules; small bundle-like arrangements were also occasionally observed. Individual NFT fibrils appeared as straight fibrils with a diameter of approximately 15 nm and constricted fibrils with a periodicity of approximately 80 nm. Ultrastructural microscopic examination of specimens stained by the modified Bielschowsky method and with the antibodies revealed silver particles and the products of the tau, ubiquitin and PHF immunoreactions on the NFT fibrils. This is the first demonstration of the fine structure of the spinal cord NFTs.

Adult↗
PubMed1992

Anchorage densities associated with hemidesmosome-like structures in perivascular reactive astrocytes.

Electron microscopical examination of devastated and reticular gliosis-replaced areas of two human brains revealed novel anchorage densities (ADs) associated with hemidesmosome-like structures (HDLSs) in perivascular astrocytes; the densities, 200-300 nm away from the cell membrane overlying the basal lamina, ran parallel to the membrane. The subplasmalemmal ADs usually received fibrils from the main stream of the deeply located glial fibrils, and sent isolated 13- to 16-nm fibrils roughly perpendicularly to the unusually prominent and frequently continuous HDLSs on the inner leaflet of the cell membrane, undercoated by a thickened basal lamina. The variable profiles of the ADs indicated that they were cell membrane-connected sheets or meshes that were virtually completely composed of bundles of glial fibrils intercrossing at variable angles or running roughly parallel to one another. All these findings suggest that the ADs may provide a significant support to the cell membrane facing the perivascular space.

Adult↗