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Biomedical subjects

K Nomoto

Publications and source records attributed to K Nomoto.

At least 307 records · Page 17Linked to original sources
PubMed1994

Early assessment of reperfusion therapy using cardiac troponin T.

OBJECTIVES: The purpose of this study was to investigate the utility of cardiac troponin T for early assessment of reperfusion therapy. BACKGROUND: Several biochemical markers are used for early noninvasive detection of reperfusion during intravenous thrombolytic therapy. However, cardiac troponin T, a new myocardial-specific marker, has not been used previously for this purpose. METHODS: We measured troponin T and creatine kinase, MB isoenzyme (CK-MB) levels in 38 patients with acute myocardial infarction whose infarct-related artery was totally occluded before reperfusion therapy. Subjects comprised 14 patients with successful angioplasty (group 1), 12 patients with successful thrombolytic therapy (group 2) and 12 patients with unsuccessful attempted reperfusion (group 3). Blood samples were taken every 15 min, and coronary angiography was performed every 5 to 8 min until 60 min after reperfusion (groups 1 and 2) or after the initiation of treatment (group 3). We calculated the increase in troponin T (delta troponin T) and CK-MB (delta CK-MB) 60 min after treatment was initiated and 60 min after reperfusion in groups 1 and 2. RESULTS: Mean (+/- SD) delta troponin T and delta CK-MB levels were 9.35 +/- 7.83 ng/ml and 125 +/- 83 mU/ml in group 1 and 3.23 +/- 3.08 ng/ml and 130 +/- 137 mU/ml in group 2, respectively, 60 min after treatment and were 10.1 +/- 8.35 ng/ml and 131 +/- 84 mU/ml in group 1 and 6.84 +/- 8.30 ng/ml and 158 +/- 146 mU/ml in group 2, respectively, 60 min after reperfusion. These values were significantly higher than those 60 min after treatment in group 3: 0.16 +/- 0.19 ng/ml and 10 +/- 9 mU/ml, respectively. The predictive accuracy for detecting reperfusion using a threshold value of 0.50 ng/ml of delta troponin T and 25 mU/ml of delta CK-MB was 100% in group 1 and 92% in group 2 60 min after treatment, respectively. There was significant correlation between delta troponin T and delta CK-MB. CONCLUSIONS: Serial measurements of cardiac troponin T as well as of CK-MB are useful for early assessment of reperfusion therapy.

Aged↗
PubMed1994

Rapid diagnosis of coronary reperfusion by measurement of myoglobin level every 15 min in acute myocardial infarction.

OBJECTIVES: The purpose of this study was to examine whether coronary reperfusion can be diagnosed rapidly and accurately by myoglobin measurements. BACKGROUND: When intravenous thrombolysis is used for acute myocardial infarction, it is important to determine coronary reperfusion rapidly and noninvasively so that further treatment can be initiated. METHODS: We determined myoglobin, creatine kinase (CK) and creatine kinase, MB fraction (CK-MB) isoenzyme levels in 63 patients with acute myocardial infarction with total occlusion of the infarct-related artery that was confirmed by coronary angiography. Myoglobin was measured by turbidimetric latex agglutination, which has an assay time of 10 min. We measured myoglobin, CK and CK-MB every 15 min in 45 patients with and 18 patients without reperfusion. The condition of the infarct-related artery was confirmed every 5 to 8 min by coronary angiography. RESULTS: The rate of increase in myoglobin, CK, and CK-MB at 15, 30, 45 and 60 min after treatment and reperfusion was significantly higher in the reperfused than in the nonreperfused group. In the reperfused group, the rate of increase in myoglobin was significantly higher than the corresponding rate of increase in CK and CK-MB at 15, 30 and 45 min after reperfusion. When reperfusion was evaluated on the basis of a cutoff level (myoglobin > or = 2.0, CK > or = 1.8, CK-MB > or = 1.5), the predictive accuracy of myoglobin (95%) was significantly higher than that of CK (68%) and CK-MB (73%) at 15 min after reperfusion. CONCLUSIONS: Coronary reperfusion can be rapidly and accurately detected by measurement of the plasma myoglobin every 15 min.

Adult↗
PubMed1994

Suppression of mitogenic activity by stable expression of the regulatory domain of PKC beta.

The amino-terminal regulatory domain portion of each protein kinase C (PKC) family member (which in the case of PKC beta 1 includes the pseudosubstrate, C1, V1 and C2 domains) plays an important role in regulating the kinase activity of the carboxyl-terminal catalytic domain. To examine the possibility that this regulatory domain region (designated 'PAT') might have biological functions independent of the catalytic domain, we have developed derivatives of R6 cells which stably express a truncated PKC beta 1 cDNA that encodes the amino-terminal 317 amino acids, including the entire regulatory domain. These R6-plPAT cells express abundant amounts of a 38 kDa protein which binds a labeled phorbol ester, but lacks protein kinase activity. In contrast to the 79 kDa PKC beta 1 holoenzyme which, when overexpressed in R6 cells, is found mostly in the cytosol, the 38 kDa PAT protein is predominantly associated with the particulate subcellular fraction. Furthermore, the PAT protein fails to show down-regulation following treatment of R6-plPAT cells with 12-O-tetradecanoylphorbol-13-acetate (TPA). Evidence is also presented that TPA-stimulated growth is suppressed in R6-plPAT cells. These findings suggest that the PKC beta 1 regulatory domain could be involved in the suppression of mitogenic signaling.

Animals↗
PubMed1994

Antigen provoking gamma interferon production in response to Mycobacterium bovis BCG and functional difference in T-cell responses to this antigen between viable and killed BCG-immunized mice.

It has been shown that gamma interferon (IFN-gamma)-producing CD4+ T cells, which are generated only by immunization with viable bacteria, exert a significant role in protective immunity against mycobacteria in mice. In this study, we have tried to determine the antigen recognized by the T cells in search of a possible protective antigen. T cells from viable Mycobacterium bovis BCG-immunized mice were stimulated with several antigens, and IFN-gamma production was measured. Purified protein derivative and viable and killed BCG lysates caused significant IFN-gamma production, and almost the same level of IFN-gamma activity was detected in both groups stimulated with viable and killed BCG lysates. However, heat shock protein (HSP) 65 and HSP 70 were not a major antigen for IFN-gamma production. The antigen provoking IFN-gamma production is localized mainly in the membrane fraction of BCG cells, and the approximate molecular size was 18 kDa. On the other hand, T cells from killed BCG-immunized mice never responded to this antigen for IFN-gamma production, whereas they could mount a delayed-type hypersensitivity response. These results showed that the antigen provoking IFN-gamma production was present in killed as well as viable BCG. In addition to the antigen presentation by antigen-presenting cells, some kinds of differentiation factor (such as monokines) that are produced only by stimulation with viable cells seemed to be necessary for the development of IFN-gamma-producing T cells.

Animals↗
PubMed1994

Apoptosis induced in CD4+ cells expressing gp160 of human immunodeficiency virus type 1.

In a previous study (Y. Koga, M. Sasaki, H. Yoshida, H. Wigzell, G. Kimura, and K. Nomoto, J. Immunol. 144:94-102, 1990), we demonstrated that the expression of gp160, a precursor form of envelope glycoprotein of human immunodeficiency virus type 1, in CD4+ cells causes the downregulation of surface CD4 and single-cell killing by forming intracellular gp160-CD4 complex. In the present study we investigated the events that lead to cell death in CD4+ cells expressing gp160. We found that apoptosis is induced in cells undergoing single-cell death. Moreover, even the cell clone, which expresses so little gp160 that it does not exhibit any apparent cytopathic effects, such as the inhibition of cell growth, was found to be highly susceptible to the apoptosis induction by the anti-Fas monoclonal antibody.

Antigens, Surface↗
PubMed1994

Priming of immature thymocytes to CD3-mediated apoptosis by infection with murine cytomegalovirus.

Cytomegalovirus (CMV) causes severe clinical manifestations in immunocompromised hosts; however, it remains unclear whether the virus itself is a cause of immunosuppression or whether it is involved as an opportunistic bystander pathogen. This study was performed to elucidate the effect of CMV infection on the host's immune system. The double-positive thymocytes of BALB/c mice inoculated with a sublethal dose of murine CMV (MCMV) were extensively depleted by a 10-micrograms amount of anti-CD3 monoclonal antibody, while such an amount was unable to induce any apparent elimination of thymocytes in noninfected mice. In immature thymocytes of infected hosts, a markedly high level of susceptibility to apoptosis induction was found on treatment with anti-CD3 monoclonal antibody. Analysis of the signal transduction pathway of such double-positive thymocytes demonstrated a profound elevation of the intracellular Ca2+ level after anti-CD3 stimulation, implying that this aberrant mobilization of Ca2+ plays a crucial role in the signaling pathway leading these cells to an extensive apoptosis. Examination of the thymus by PCR was able to detect a low copy number of MCMV DNAs in thymic stromal cells but none at all in thymocytes. Therefore, it is suggested that a mechanism which is not associated with virus replication within the cells exerts a critical effect on rendering the thymocytes highly apoptosis sensitive in hosts infected with MCMV.

Animals↗
PubMed1994

Murine cytomegalovirus-associated pneumonitis in the lungs free of the virus.

At 4 wk after intraperitoneal inoculation of murine cytomegalovirus (MCMV) in adult BALB/c mice, MCMV remained detectable only in the salivary glands. When T cells of these mice were activated by a single injection of anti-CD3 epsilon monoclonal antibody, mice died of interstitial pneumonitis at 24-48 h after injection, accompanied by elevation of serum levels of TNF-alpha and IFN-gamma. However, MCMV remained undetectable in the lungs during the period. Simultaneous injection of cyclosporin A reduced such effects of anti-CD3. In conclusion, although the presence of MCMV in the host may be required, MCMV-associated pneumonitis is not mediated by virus in the lung but probably by the cytokines released from T cells, of which responsiveness to stimulation via CD3 molecule has been presumably modified by MCMV infection.

Animals↗
PubMed1994

Timing in administration of a heat-killed Lactobacillus casei preparation for radioprotection in mice.

A single subcutaneous injection of a preparation of heat-killed Lactobacillus casei (LC 9018), given before or after irradiation, significantly increased the survival rate of mice that had received 8.5-Gy 137Cs whole-body gamma-irradiation. A similar radioprotective effect was observed when LC 9018 was administered within the period from 2 days before irradiation to 9 h after irradiation, the pre-irradiation treatment being slightly better than the post-irradiation treatment. Increases in the weight of the spleen and in the number of endogenous spleen colonies on days 8 and 12 after irradiation suggested that the radioprotective effect was based on enhanced recovery of hematopoietic tissues. The activity of macrophage colony-stimulating factor (M-CSF) in serum was rapidly increased by the treatment and was maintained at the elevated level for 13 days. At the same time, an increased level of M-CSF mRNA was detected in the livers of the treated mice. However, LC 9018 failed to save the lives of mice when administered 3 days after irradiation, although it increased serum M-CSF as effectively as noted above. The small advantage of the pre-irradiation over the post-irradiation treatment was not explained by the increases of metallothionein in the hematopoietic tissues of the treated mice.

Adjuvants, Immunologic↗
PubMed1994

Structure-depolarizing activity relationship for achatin-I, a tetrapeptide with a D-Phe residue, and its derivatives toward the crayfish giant axon.

Achatin-I (Gly-D-Phe-Ala-Asp) is a tetrapeptide isolated from the ganglia of an African giant snail (Achatina fulica Férussac). The compound and its derivatives were synthesized, and their effects on the action potential of the crayfish giant axon elicited by electrical stimulation were examined by an intracellular recording method. The membrane potential after the action potential had fallen was elevated by some compounds at an acidic but not neutral pH level. An analysis of the structure-activity relationship for the activity to elevate the afterpotential at an acidic pH level, suggests that the factors favorable for activity were the beta-turn conformation, a beta- or gamma-carboxyl group in the C-terminal residue, appropriate hydrophobicity and/or bulkiness in the protecting groups for the alpha-amino group at the N-terminus, and the number of negative charges in the entire molecule.

Action Potentials↗
PubMed1994

Differentiation and function of intestinal intraepithelial lymphocytes.

Intestinal intraepithelial lymphocytes (i-IEL) are phenotypically diverse and consist of both thymically derived and extrathymically derived cells. Extrathymically derived i-IEL are clearly different from thymically derived peripheral T cells in their phenotype and repertoire selection. The major locus of differentiation of extrathymically derived i-IEL appears to be the intestinal epithelium because recombination activating gene (RAG)-1 is expressed in CD3- i-IEL. Extrathymic differentiation however does not imply independence from the thymus as athymic mice have increased numbers of CD3-CD8- and CD3-CD8 alpha alpha + i-IEL but decreased numbers of CD3+CD8 alpha alpha+ i-IEL when compared to euthymic mice. We speculate from these results that thymus-derived cytokine(s)/factor(s) may support differentiation from CD3-CD8 alpha alpha + to CD3+CD8 alpha alpha + i-IEL in the intestinal epithelium. i-IEL seem to have some role in immune surveillance because they reside at a site which may represent a first line of defense against pathogenic organisms. This idea is supported by the reports showing in vivo activation of i-IEL under conditions of intestinal infection or tumor-bearing state. In vitro analyses showed cytotoxicity and cytokine production of i-IEL but their true function(s) in vivo is(are) not well known. Clearly more analysis on the in vivo function(s) of i-IEL are needed in order to clarify the true role(s) of i-IEL.

Animals↗
PubMed1994

Augmentation of the resistance against Listeria monocytogenes by oral administration of a hot water extract of Chlorella vulgaris in mice.

Oral administration of a hot water extract of Chlorella vulgaris(CVE)(20mg/mouse, 10 consecutive days) augmented the resistance against an i.p. infection with Listeria monocytogenes in mice. The numbers of bacteria in a CVE-administered group were significantly lower in the peritoneal cavity or spleen than those in a control group. FCM analysis revealed that gamma delta +Thy1.2+ cells in the nonadherent PEC from CVE-administered mice increased more prominently in number at the early stage on day 3 or on day 5 after infection as compared with those in control mice. The increment of gamma delta +Thy1.2+ T cells was also evident in spleen in CVE-administered mice at this stage after infection. The proportion of TCR alpha beta +Thy1.2+ T cells in the nonadherent PEC of a control group increased from 13% on day 0 to 49% at the late stage on day 10 after infection, whereas the proportion of TCR alpha beta +Thy1.2+ T cells in the nonadherent PEC in CVE-administered mice increased to 64% on this stage after infection in association with augmentation of DTH response to Listeria. These results suggest that CVE-administration effectively augment cell-mediated immunity against Listeria through the increment of gamma delta + T cells in the early phase and the increment of alpha beta + T cells in the late phase after listerial infection.

Administration, Oral↗
PubMed1994

Augmentation of NK activity after oral administration of a traditional Chinese medicine, xiao-chai-hu-tang (shosaiko-to).

We have shown that a traditional Chinese medicine, Xiao-chai-hu-tang (Japanese name: Shosaiko-to) augments natural killer (NK)1 activity in mice. The maximum augmentation of NK activity in the peripheral blood and liver was observed at 12 hr after administration of Shosaiko-to. NK activity was augmented by Shosaiko-to dose-dependently. The augmentation became significantly positive at a dose of 500 mg/kg, and the maximum effect was observed at a dose of 1000 mg/kg. The augmentation of NK activity appeared at first in the liver from 6 hr after administration of Shosaiko-to and became detectable later in the peripheral blood from 12 hr after the administration. Activation of NK cells by Shosaiko-to may occur in the liver and subsequently the activated NK cells may be supplied to the peripheral blood. Changes in percentages of cell surface markers (asialo GM1, CD3, CD4, CD8) after Shosaiko-to treatment were hardly detected, but augmentation of NK activity induced by Shosaiko-to was abrogated by anti-asialo GM1 antibody treatment before the cytotoxicity assay. In addition, cytotoxic activity to P-815 target cells was not detected in Shosaiko-to treated mice. Augmentation of NK activity by Shosaiko-to is probably mediated by functional activation of classical NK cells of asialo GM1+ phenotype. These results suggest that augmentation of NK activity in the liver is one of mechanisms involved in clinical efficacy of Shosaiko-to in patients with virus chronic hepatitis.

Animals↗
PubMed1994

[Influence of Lactobacillus casei on rat bladder carcinogenesis].

The inhibitory effect of Lactobacillus casei (L. casei) in superficial bladder tumors was investigated in an experimental study using N-butyl-N (4-hydroxybutyl) nitrosamine (BBN)-induced rat bladder cancer as an experimental system. The study consisted of two experiments; in a short-term experiment, the inhibitory effect of 6-week treatment with L. casei was assessed in vitro in terms of the capacity for agglutination by concanavalin A (Con A) of bladder epithelial cells in their incipient stage of malignant transformation induced by 1-week exposure to BBN. As a result, the number of bladder epithelial cell aggregates caused by Con A was significantly smaller in the L. casei-treated group than in the non-L. casei-treated group (p < 0.001). In a long-term experiment, treatment with L. casei of varying duration was investigated for effectiveness against bladder tumors induced by 7-weeks exposure to BBN that arose 22 weeks. The results indicate that both bladder weight and tumor volume per organ were significantly lower in the L. casei-treated than non-L. casei-treated group (p < 0.05). The inhibitory effect on these parameters was more pronounced with treatment with L. casei of longer duration. While there was no significant difference among the treatment groups in the degree of extension of induced malignancy, tumors with a high degree of extension (T1b, T2) developed only in the non-L. casei-treated group. The degree of malignancy of induced tumors was significantly lower in those groups receiving L. casei while BBN was being administered as compared to the non-L. casei-treated group (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

A myomodulin-CARP-related peptide isolated from a polychaete annelid, Perinereis vancaurica.

Myomodulin-CARP-family peptides have been isolated only from molluscs. In the present study, a heptapeptide, Ala-Met-Gly-Met-Leu-Arg-Met-NH2, termed Pev-myomodulin, was isolated from a polychaete annelid, Perinereis vancaurica using the esophagus of the animal as the bioassay system. The sequence of the annelid peptide is highly homologous with those of the myomodulin-CARP-family peptides found in molluscs. The annelid peptide is regarded as a member of the myomodulin-CARP family, though all the molluscan peptides have a Leu-NH2 at their C-termini. The annelid peptide showed a potnet contractile action on the esophagus of the annelid. The peptide may be an excitatory neuromediator involved in the regulation of the esophagus. Among various myomodulin-CARP-family peptides and their analogues, the annelid peptide showed the most potent contractile action on the esophagus. Replacement of the C-terminal Met-NH2 of the annelid peptide with a Leu-NH2 decreased its contractile potency, while replacement of the C-terminal Leu-NH2 of myomodulin and CARP with a Met-NH2 increased their potency. The C-terminal Met-NH2 of the annelid peptide seems to be important, but not essential, for exhibiting its contractile activity on the esophagus. On the anterior byssus retractor muscle of the bivalve mollusc Mytilus edulis, the annelid peptide showed catch-relaxing and contraction-modulating effects qualitatively similar to those of the authentic peptide CARP, though the annelid peptide was less potent than CARP.

Amino Acid Sequence↗
PubMed1994

Inhibition of skin xenograft rejection by depleting T-cell receptor alpha beta-bearing cells without T-cell receptor gamma delta-bearing cells or natural killer cells by monoclonal antibody.

We compared the effects of in vivo administration of the anti-T-cell receptor (TCR) alpha beta monoclonal antibody (mAb) (H57-597) to those of the anti-CD3 mAb (145-2C11), with or without anti-NK1.1 mAb (PK136), on xenogeneic skin graft survival in mice. In anti-TCR alpha beta mAb-treated B6 mice, F344 rat skin grafts survived for about 54 days, whereas in anti-CD3 mAb-treated B6 mice with or without anti-NK1.1 mAb treatment grafts survived about 25 days. In anti-TCR alpha beta mAb-treated B6 mice, TCR alpha beta-bearing T-lymphocyte function was completely abrogated, although TCR gamma delta-bearing T-lymphocyte function was still intact on day 9. In the anti-CD3 mAb-treated mice, the functions of both types of T lymphocytes were completely abrogated. On day 32, when most of the skin xenografts had been rejected in the anti-CD3 mAb-treated mice, the functions of both T lymphocytes had recovered considerably, and could actually respond to F344 antigens. In contrast, the function of TCR alpha beta-bearing cells had only partially recovered in the anti-TCR alpha beta mAb-treated mice. Finally, natural killer (NK) activity in the anti-TCR alpha beta mAb-treated mice was intact on day 32, when rat skin grafts still survived. In contrast, NK activity in the anti-CD3 mAb plus anti-NK1.1 mAb-treated mice did not recover on day 32, when skin xenografts had already been rejected. These results suggest that TCR gamma delta-bearing T cells and NK cells by themselves, at least in the absence of TCR alpha beta-bearing T cells, do not mediate xenogeneic skin graft rejection in mouse/rat combinations.

Animals↗
PubMed1994

V delta 5+ T cells of BALB/c mice recognize the murine heat shock protein 60 target cell specificity.

The purpose of this paper was to study the gamma delta T-cell receptor repertoire and target specificity following stimulation of peripheral T cells of BALB/c mice with autologous or bacterial ligands. The expression of V gamma and V delta chain families in T cells that had been expanded by stimulation in syngeneic mixed lymphocyte culture or with purified protein derivative (PPD) was determined by the semiquantitative DNA polymerase chain reaction (PCR) method. Responder T cells to either of these stimuli strongly expressed both V delta 5 and V delta 6 genes. However, addition of the ML 30 anti-murine heat shock protein (hsp) 60 monoclonal antibody (mAb) to the cell culture selectively inhibited only the expansion of V delta 5 T cells. A V delta 5 T-cell hybridoma (KMT-5), which recognized syngeneic splenic and fibrosarcoma Meth A cells but not allogeneic cells, was produced by cell fusion from autoreactive blast cells. Incubation of the KMT-5 hybridoma in the presence of ML 30 antibody blocked the stimulation of interleukin-2 (IL-2) secretion by syngeneic target cells. It was also found that the DNA of KMT-5 hybridoma and of the autoreactive gamma delta T cells contained the BALB/c invariant delta (BID) chain sequence. It is concluded from these results that BALB/c peripheral V delta 5 T cells recognize an autologous hsp 60 target specificity in a V delta-gene restricted manner. We also propose that T cells of this V gene family may be involved in the immune surveillance of certain tumours and intracellular infections.

Animals↗
PubMed1994

[A clinical study on fluconazole against pulmonary mycosis associated with respiratory diseases].

In 34 hospitals in Kyushu area, the clinical effects and safety of fluconazole (FLCZ) against pulmonary mycosis were studied. To a total of 108 patients with respiratory diseases was FLCZ administered. The results were as follows. 1. Sixty-six cases were evaluable for the clinical efficacy of FLCZ. In 8 cases of pulmonary cryptococcosis, the clinical efficacy rate was 100% (8/8). In 58 cases of pulmonary aspergillosis, it was 43.1% (25/38). Overall, the clinical efficacy rate was 50% (33/66). 2. Fungi were eliminated in 3 of 6 cases in which Cryptococcus was detected, and were eliminated in 8 and reduced in 4 of 30 cases in which Aspergillus spp. including A. fumigatus were detected. 3. Side effects were observed in 5 of 87 cases (5.7%), none of them was serious, however. Abnormal results of laboratory tests that might be related to the FLCZ administration were observed in 5 cases (5.7%). 4. From these results, fluconazole appears to be a potent antifungal agent for treatment of pulmonary mycosis.

Adult↗