Biomedical subjects

K Nomoto

Publications and source records attributed to K Nomoto.

At least 181 records · Page 10Linked to original sources

PubMed1997

ATP-induced dynamic fluorescence changes of a N-[p-(2-benzimidazolyl)phenyl]maleimide probe at Cys241 in the alpha-chain of pig stomach H+,K+-ATPase.

H+,K+-ATPase preparations from pig stomach were modified with a sulfhydryl fluorescence reagent, N-[p-(2-benzimidazolyl)phenyl] maleimide (BIPM). The addition of ATP to the modified enzyme preparations in the presence of Mg2+ decreased the BIPM fluorescence but increased the Trp fluorescence. After exhaustion of ATP, the fluorescence intensities increased and decreased to the original levels, respectively. The results of stopped flow and rapid quenching experiments suggested that the decrease in BIPM fluorescence (36/s) was accompanied by binding of Mg2+ and ATP or phosphorylation (35 36/s) which was followed by slower increases in Trp fluorescence (24/s) and light scattering (20/s). Tosylphenylalanyl chloromethyl ketone-trypsin treatment of the modified preparations, which showed an about 1% decrease in BIPM fluorescence accompanying phosphorylation, gave one major fluorescent peptide peak on reverse-phase chromatography. Amino acid sequence analysis of the peptide revealed the following sequence, Ser-Pro-Glu-X-Thr-His-Glu-Ser-Pro-Leu-Glu-Thr-Arg. On comparison with the amino acid sequence deduced from cDNA from pig stomach [Maeda, M., Ishizaki, J., and Futai, M. (1988) Biochem. Biophys. Res. Commun. 157, 203-209], X was shown to correspond to Cys241 of the alpha-chain in H+,K+-ATPase. These data and others suggest that the decrease in BIPM fluorescence at Cys241 reflects some molecular event triggered by the binding of ATP with Mg2+ and/or phosphorylation, whereas the increases in the intrinsic Trp fluorescence and light scattering reflect one after phosphorylation.

Adenosine Triphosphate↗

PubMed1997

Serum levels of cardiac troponin I and troponin T in estimating myocardial infarct size soon after reperfusion.

BACKGROUND: Cardiac troponin I (TnI) and troponin T (TnT) are highly specific myocardial markers. OBJECTIVE: To determine whether their serum levels can be used to estimate myocardial infarct size soon after reperfusion. METHODS: We measured the serum levels of TnI, TnT, and creatine kinase every 3 h, and the serum cardiac myosin light chain I (MLCI) every 24 h, in 42 patients with acute myocardial infarction in whom reperfusion therapy had successfully been performed. We calculated the severity of regional hypokinesis by analyzing the follow-up ventriculograms with the centerline method. RESULTS: The time from reperfusion to the peak level for TnI was 6.1 +/- 3.5 h, significantly shorter than those for creatine kinase (7.5 +/- 4.1 h) and MLCI (55 +/- 28 h). The time to peak level for TnT (6.8 +/- 4.0 h) differed significantly from that for MLCI but not from that for creatine kinase. There was a significant correlation between the peak levels of TnI and TnT (r = 0.86). The peak TnI and TnT levels were correlated well to the peak creatine kinase level (r = 0.67 and 0.69, respectively), total creatine kinase release (r = 0.66 and 0.66), and the peak MLCI level (r = 0.71 and 0.80). We observed excellent correlations between the peak levels of TnI and TnT, and regional hypokinesis (r = -0.84 and -0.85, respectively). These were comparable to the correlations between regional hypokinesis and the peak creatine kinase level (r = 0.75), total creatine kinase release (r = -0.72), and the peak MLCI level (r = -0.76). CONCLUSIONS: These results suggest that the peak serum levels of TnI and TnT in patients with successful reperfusion are accurate and early indices of infarct size.

Angioplasty, Balloon, Coronary↗

PubMed1997

The induction of cytotoxic T lymphocytes against HLA-A locus-matched lung adenocarcinoma in patients with non-small cell lung cancer.

To induce cytotoxic T lymphocytes (CTL) against non-small cell lung cancer (NSCLC) efficiently, the induction of CTL was attempted using HLA-A locus-shared allogeneic NSCLC cells. T cells derived from either tumor tissue specimens or the regional lymph nodes of patients with NSCLC were stimulated twice or three times with an HLA-A2/A24-positive NSCLC cell line (PC-9), and thereafter the cytotoxic activity was examined by 51Cr-release assay. In patients with HLA-A24/ adenocarcinoma, anti-PC-9 cytotoxicity was induced in all 6 patients tested. Anti-PC-9 cytotoxicity was induced in 2 out of 5 patients with HLA-A2 (A24-)/adenocarcinoma, in 2 out of 4 patients with HLA-A24/squamous cell carcinoma, and 1 of 2 patients with HLA-A2/squamous cell carcinoma. The cytotoxic activity was observed to kill PC-9 selectively, not other NSCLC lines, and the activity was substantially blocked by anti-MHC class I antibody, but not by anti-MHC class II antibody. The PC-9-specific CTL produced gamma-interferon in response to autologous tumor cells. These results indicated that the anti-PC-9 cytotoxicity was mediated by cytotoxic T lymphocytes that may recognize the T cell epitope(s) shared and presented by HLA-A2 and/or HLA-A24-positive NSCLC.

Adenocarcinoma↗

PubMed1997

Case report: primary hepatic lymphoma associated with chronic liver disease.

We report on a case of primary hepatic lymphoma that developed in a patient with chronic hepatitis C. Given that Japan is an area endemic for both hepatitis B and C viruses, we reviewed 51 Japanese cases of primary hepatic lymphoma, addressing the question as to whether the Japanese cases have unique characteristics and whether there is a causal relationship to the presence of chronic liver disease. Primary hepatic lymphoma most commonly affected middle-aged males. Presenting symptoms and physical findings were non-specific. Aminotransferases tended to stay in the low range compared with marked increases in lactate dehydrogenase. Sixteen patients (31%) had chronic liver disease, eight had liver cirrhosis and eight had chronic hepatitis, suggesting that there is a possible aetiological link between chronic liver disease and primary hepatic lymphoma.

Adult↗

PubMed1997

An association between salivary gland disease and serological abnormalities in Sjögren's syndrome.

In the labial salivary glands (LSGs) of 16 primary and 18 secondary Sjögren's syndrome (SS) patients, infiltrating lymphocytes were histologically and immunohistochemically examined; also, the serum levels of rheumatoid factor, antinuclear antibodies, anti-DNA antibodies, anti-SS-A and anti-SS-B antibodies, and immunoglobulins (including IgG, IgM and IgA) were all assayed. An immunohistochemical analysis of the lymphocyte subsets in LSGs revealed that severe lymphocytic infiltration was frequently accompanied by marked B cell accumulation both in primary and secondary SS patients. Furthermore, local B cell accumulation was also closely associated with elevated levels of anti-SS-A and anti-SS-B antibodies and IgG, and this association was statistically significant in the group with primary SS but not in the group with secondary SS. Thus, local lymphocytic infiltration, especially B cell accumulation, in the salivary glands is suggested to be involved in serological abnormalities in primary SS, while complicated autoimmune diseases other than SS may also be involved in serological abnormalities in secondary SS.

Adolescent↗

PubMed1997

Wide range of molecular weight distribution of mitogenic substance(s) in the hot water extract of a Chinese herbal medicine, Bupleurum chinense.

In this study, we examined the contribution of lignin-like materials in lower molecular weight (MW) fractions from the hot water extract of Bupleuri Radix (Bupleurum chinense) (HWE-BR) for their immunopharmacological activities. Mitogenic activity was detected in all the fractions of MW ranges: lower than 1.0 kDa, 1.0-3.5 kDa, 3.5-10 kDa, and 10-50 kDa. After NaClO2 treatment of these subfractions, UV spectra, ESR spectra, mitogenic activities on murine B-cells, and the activity of inducing nitric oxide in RAW 264.7 cells were significantly reduced, suggesting that lignin-like polyphenolic substance(s) of various MW might take part in these activities. The intensity of ESR spectra and mitogenic activities were stronger in higher MW subfractions, thus the content of stable radical species and/or the degrees of polymerization would be important for their immunopharmacological activities.

Animals↗

PubMed1997

Acceleration of granulocytic cell recovery in irradiated mice by a single subcutaneous injection of a heat-killed Lactobacillus casei preparation.

Flow cytometric analysis showed that the treatment of irradiated mice with a heat-killed Lactobacillus casei preparation (LC 9018) accelerated the recovery of granulocytic cell populations in peripheral blood, spleen and femur bone marrow. The recovery of the lymphocytic cell population was not accelerated while the recovery of the B-lymphocytic cell population was inhibited. Histological analysis also showed that the LC-9018 treatment markedly enhanced granulopoiesis in the spleen and bone marrow of irradiated mice. The same LC-9018 treatment significantly increased 30-day survival rates of athymic nude mice after lethal whole-body irradiation. The recovery of the granulocytic cell population in peripheral blood of irradiated athymic nude mice was also accelerated by LC-9018 treatment. Our results suggest that LC 9018 protected lethally irradiated mice from bone marrow death by enhancing granulopoiesis rather than lymphopoiesis and that the contribution of activated T lymphocytes to the enhancement of the granulopoiesis was small.

Adjuvants, Immunologic↗

PubMed1997

Nitric oxide metabolite in pregnant women before and after delivery.

BACKGROUND: During pregnancy, systemic vascular resistance as well as vascular sensitivity to vasoconstrictive agents decreases in pregnant women. METHODS AND MATERIALS: The vascular resistance of the fetus is also maintained in the presence of low blood pressure. We believe that the main factors in this phenomenon are nitric oxide (NO), along with prostaglandin. NO is an unstable compound with a short half-life;it is easily converted to nitrite (NO2) and nitrate (NO3). Since NO cannot be precisely quantified, we measured the NO2 concentration in maternal blood just before and after delivery and compared in with the values of non-pregnant women. RESULTS: NO2 concentrations in the 13 women who received cesarean deliveries under epidural anesthesia were not significantly changed by the anesthesia. Before anesthesia the NO2 concentration was 216 +/- 115 pmol/mg protein, and after the induction of anesthesia, but before surgery, it was 218 +/- 112 pmol/mg protein. The NO2 concentration then fell significantly after the surgery to 174 +/- 75 pmol/mg protein (p < 0.05). In addition, after vaginal delivery, in 17 other patients we observed marked decreases in NO2 concentration, falling from 160 +/- 82 to 125 +/- 61 pmol/mg protein (p < 0.05). These values were significantly higher than those of non-pregnant women (3.4 +/- 2.1 microM, 33 +/- 22 pmol/mg protein) (p < or = 0.0001). CONCLUSION: These results suggest that NO contributes to the low vascular resistance observed in the mother and fetus during pregnancy.

Adult↗

PubMed1997

[Effects of long-term ethanol administration (1). Effects of long-term ethanol administration on kidney studied at several periods of time during the administration].

The kidney is an important organ having not only excreting function but also other functions such as production of the substances that activates a living body, enzymatic reaction, immunization etc. For several years we have carried out experiments of ethanol administration to rats and involved observations of various organs including the kidney. Thus we have recognized no small effect of ethanol on the kidney. After ethanol administration, the ethanol and its metabolites go through kidneys and are excreted into urine, and their content of the urine is higher than that of the blood. Their content of the kidney is higher than that of the liver. In view of all these facts, the ethanol effect on kidney is easily assumed. In this study a comparison between effect of ethanol on kidney and that of the liver was made at several periods of time during the administration. Under short, a week ethanol administration, the direct action that exerts on cells is as follows: in the kidney swelling of glomerula and tubules, proliferation of mesangial cells, and hyaline drop in tubular epithelial cells are seen; in the liver storing of small fat drops and enlargement of Kupffer cells are observed. Under long, two month administration, products like ethanol metabolites-protein adducts and hyaline in tubular epithelial cells as their removal reaction are observed in the kidney; in the liver, enlargement of Kupffer cells in shown. Under long administration of six and eleven months, kidney shows atrophy of tubular epithelial cells, urinary casts, and cell infiltration to interstitial tissue; liver shows fat storing and bile duct proliferation. These changes found through the effects of age appear in the experimented rats earlier than the control. In addition thickening of basement membrane of glomerulus, PAS positive deposits in glomerulus, and proliferation of mesangial cell are observed in the kidney. It was apparently observed that effects of ethanol on the kidney appeared earlier than those on the liver.

Administration, Oral↗

PubMed1997

[Effect of long-term ethanol administration (2). Free type and bound type ethanol and related substances contents of the urine from ethanol administrated rats, indices in the serum, and renal tissues].

Histological effects of ethanol on the kidney were published in our previous report. In the present paper, results of the following measurement will be reported: contents of ethanol and related substances in the urine, both free and bound types, collected during the periods from 30 minutes to 11 hours after ethanol administration to rats, and ACE, alpha-GST, LPO, 25(OH)-D3, 1 alpha-25(OH)2-D3, 24, 25(OH)2-D3 in the serum of rats which had ethanol every day for a month. These will be reported together with histological observation of the kidney excised immediately after the blood sample was collected. The measurement of free and bound types ethanol, acetaldehyde, acetone and methanol in the urine was made up to 11 hours after administration of 4 g/kg b.w./day, p.o. and its results showed the highest contents at 9 hours after the administration. Bound type acetic acid showed the high contents at both 90 minutes and 9 hours after the administration. In 11 hours free type ethanol and acetaldehyde recovered their pre-administration value but as to the bound type only acetic acid recovered it. In the serum of the rats which were ethanol 4 g/kg b.w./day, oral administrated for a mouth, ACE showed significantly high value and 1 alpha, 25(OH)2-D3 and 24, 25(OH)2-D3 showed significantly low value relative to the control. Also alpha-GST showed a low value. In the kidney of the same rats the following changes were observed: swelling of glomerulus, thickening of basement membrane of glomerulus, PAS positive deposits in glomerulus, proliferation of mesangial cell, proliferation of juxtaglomenular cell, dilation of tubular lumen, swelling of tubular epithelial cell, its falling, hyaline droplet in tubular epithelial cell, cell infiltration to interstitial tissue, and basophilic tubule. There was not only difference between findings in the control and those in the liver and the brain of the rats which showed changes above-mentioned. As described above, changes were seen in the renal tissue caused by ethanol administration and in this connection changes in indices related to renal function were observed, too. Furthermore, urinary ethanol and related substances, not only free type but also bound type, that went through the kidney were observed for a long period time. The bound type, in particular, was observed for longer duration and hence effects of ethanol on the kidney were surely assumed. Presently longer term experiments are proceeding and other indices connected with renal functions are being studied.

Administration, Oral↗

PubMed1997

[Multiple solitary lesions in deep white matter in the early stage of Creutzfeldt-Jakob disease. A case report].

A 56-year-old housewife was admitted to our hospital because of involuntary movement on her left arm. Her neurological examination on admission showed mild weakness of her left arm and cerebellar ataxia. She developed periodic synchronous discharge on electroencephalogram and her cerebrospinal fluid revealed elevated level of neuron-specific enolase. Thereafter she developed dementia, followed by apallic state and diagnosed as having Creutzfeldt-Jakob disease (CJD). Interestingly, her MRI on admission revealed multiple solitary lesions in deep cerebral white matter, which were detected as high signal intensity by T2 weighed image. A few months later, these lesions tended to extend, and finally fused around the lateral ventricle in parallel with remarkable cortical atrophy. We excluded other diseases such as cerebrovascular disorders. Finally, we concluded the white matter change seen from early stage in this case may be the lesion associated with CJD, and the CJD case with early white matter changes has been seldomely described.

Atrophy↗

PubMed1996

Regulatory T cells in maintenance and reversal of peripheral tolerance in vivo.

Whether regulatory T cells could suppress the immune responses to an unrelated Ag and could induce tolerance to that Ag was investigated. In female B6 (I-Ab) mice tolerized to MHC class II I-Abm12 (bm12) alloantigen by cyclophosphamide-induced system, regulatory T cells specific for bm12 Ag were induced. These regulatory T cells suppressed in vivo immune responses to an unrelated Ag (male Ag) that was co-expressed with bm12 Ag on the same graft. However, the immune responses to male Ag suppressed by regulatory T cells were reverted by immunization with male Ag alone, indicating regulatory T cells suppressed the induction of immune responses to the unrelated Ag co-expressed with suppressogenic determinant, but did not inactivate T cells specific for that third Ag, such as clonal anergy or deletion. These results provided that minor Ag adjacent to major Ag, even if they were expressed on the professional APC, could be suppressed in the periphery, and the responses to those minor Ag could be activated when the suppression mechanism was abrogated or ineffective.

Animals↗

PubMed1996

Molecular cloning and analysis of the 5'-flanking region of the rat PP1 alpha gene.

We have cloned an 8 kbp genomic fragment of 5'-flanking region of the gene encoding the catalytic subunit of rat protein phosphatase 1 alpha. Neither CAAT box nor TATA box was detected but a 300 bp high GC region containing nine Sp1 transcription factor binding sites is present immediately upstream of the translation start site, demonstrating that PP1 alpha is a housekeeping gene. Luciferase reporter assay showed that transcription of PP1 alpha is controlled at the high GC region.

3T3 Cells↗

PubMed1996

Extrathymic development of self-reactive gamma(delta) T cells in athymic BALB/c nu/nu mice.

In the present report, we demonstrated that extrathymic gamma(delta) T cells proliferated in the mixed culture of lymph node cells of BALB/c nu/nu mice and irradiated syngeneic spleen cells (syngeneic MLR). Reverse transcription-polymerase chain reaction (RT-PCR) analyses revealed that V(delta)5 and V(delta)6 were dominantly expressed by the gamma(delta) T cells from the syngeneic MLR. Furthermore, the syngeneic MLR may expand V(delta)5+ T cells with BALB invariant delta (BID) sequence which is specifically detected in BALB background mice because V(delta)5 RT-PCR products from syngeneic MLR were digested with an AluI restriction enzyme which cut the D(delta)2-J(delta)1 junction of the BID sequence but not those of most non-BID V(delta)5 sequences. Interestingly, anti-mycobacterial and mammalian heat shock protein (Hsp) 60 mAb ML30 suppressed the generation of V(delta)5 with an AluI site in syngeneic MLR. These results suggest that extrathymically derived V(delta)5+ and V(delta)6+ gamma(delta) T cells recognize BALB/c self antigens and that the Hsp60 or an Hsp60-related molecule may be involved in the anti-self response of V(delta)5+ BID+ gamma(delta) T cells.

Animals↗

PubMed1996

Annetocin, an annelid oxytocin-related peptide, induces egg-laying behavior in the earthworm, Eisenia foetida.

Annetocin, an oxytocin-related peptide which we isolated from the earthworm Eisenia foetida, induced a series of egg-laying-related behaviors in the earthworms. These stereotyped behaviors consisted of well-defined rotatory movements, characteristic body-shape changes, and mucous secretion from the clitellum. Each of these behaviors is known to be associated with formation of the cocoon in which eggs are deposited. In fact, some of the earthworms injected with annetocin (> 5 nmol) laid eggs. Such egg-laying-related behaviors except for oviposition were also induced by oxytocin, but not by Arg-vasopressin and some other bioactive peptides isolated from E. foetida. Furthermore, annetocin also induced these egg-laying-like behaviors in the leech Whitmania pigra, but not in the polychaete Perinereis vancaurica. These results suggest that annetocin plays some key role in triggering stereotyped egg-laying behaviors in terrestrial or fresh-water annelids that have the clitella.

Amino Acid Sequence↗

PubMed1996

Induction of apoptosis by calmodulin-dependent intracellular Ca2+ elevation in CD4+ cells expressing gp 160 of HIV.

Human CD4+ cell clones expressing either gp160 or gp120 of HIV-1 under the transcriptional control of an inducible promoter were used to examine the role of Ca2+ signalling in the induction of apoptosis by envelope glycoproteins. Singlecell killing with apoptosis was induced in the cells expressing gp 160 while no such apoptosis was found in the cells expressing gp 120. An increase of intracellular Ca2+ was found in the gp 160-expressing cells but not in the gp 120-expressing cells as determined by Intracellular Ca2+ imaging analysis before the appearance of DNA fragmentation. W7, a calmodulin antagonist, blocked the elevation of Ca2+ as well as the resultant DNA fragmentation, which thus implies that the calmodulin-dependent intracellular Ca2+ release system is first activated by gp 160 and thereafter apoptosis takes place. The above results thus indicate that Ca2+ signalling plays a crucial role in the apoptosis accompanying the single-cell death induced by gp 160 in CD4+ cells.

Apoptosis↗

PubMed1996

Enhanced generation of NK cells with intact cytotoxic function in CD45 exon 6-deficient mice.

CD45 is a cell membrane-type protein tyrosine phosphatase that is essential for Ag receptor-mediated signaling in both T and B lymphocytes. To characterize roles of CD45 molecules in murine NK cells, we analyzed the development and the cytotoxic functions of NK cells in mice lacking CD45 exon 6 (CD45 -/-). A markedly increased number of NK cells was observed in spleens of the CD45 -/- mice, despite no CD45 surface expression on the NK cells. From the results of mixed bone marrow chimera experiments, it was demonstrated that the expansion of NK cells in CD45 -/- mice was due to the influence of disappeared expression of CD45 in the NK cells per se, but not to the modulation of environmental factors. The NK cells in the CD45 -/- mice had normal cytotoxic activities, including NK and Ab-dependent cell-mediated cytotoxicity activities comparable with those in normal mice (CD45 +/+). Additionally, the CD45 -/- NK cells could functionally differentiate to lymphokine-activated killer cells by culturing with a high dose of IL-2, despite a lack of induced expression of B220. Therefore, these results suggest that CD45 is involved in NK cell development, but is not essential for cytotoxic activities and Fc gamma R-mediated signaling in NK cells.

Animals↗

PubMed1996

Thymus ontogeny and the development of TCR alpha beta intestinal intraepithelial lymphocytes.

Murine T cell receptor (TCR) alpha beta intestinal intraepithelial lymphocytes (IEL), which express the CD8 molecule as a homodimer (CD8 alpha alpha), can be divided into two subsets: those which are CD4+ (CD4+CD8+alpha alpha) and those which are CD4- (CD4-CD8+alpha alpha). Here, we demonstrate that most TCR alpha beta CD4+CD8+alpha alpha IEL and TCR alpha beta CD4-CD8+alpha alpha IEL subsets appear to be of thymus origin, as neonatal thymectomy of BALB/c mice on Day 3 nearly eliminated both subsets. To further support this hypothesis, we demonstrate by grafting the thymus of CBF1 (BALB/c x C57BL/6) mice into nude mice that the thymus is capable of generating both TCR alpha beta CD4-CD8+alpha alpha IEL and TCR alpha beta CD4+CD8+alpha alpha IEL. However, which of the two TCR alpha beta IEL subsets is generated depends largely on the age of the thymus. The thymus from fetal up to 2 weeks of age generates predominantly TCR alpha beta CD4-CD8+alpha alpha IEL, but very scant amounts CD4+CD8+alpha alpha IEL. In contrast, the thymus after 2 weeks of age generates very little TCR alpha beta CD4-CD8+alpha alpha IEL, but generates an abundant amount of TCR alpha beta CD4+CD8+alpha alpha IEL. These results are consistent with the observation in euthymic mice that TCR alpha beta CD4-CD8+alpha alpha IEL precede the appearance of TCR alpha beta CD4+CD8+alpha alpha IEL by several weeks, thus further suggesting that the thymus is the major source of both TCR alpha beta IEL subsets.

Aging↗