Biomedical subjects

Y Yamamura

Publications and source records attributed to Y Yamamura.

At least 19 recordsLinked to original sources

PubMed1992

Distinct downstream signaling mechanism between erythropoietin receptor and interleukin-2 receptor.

Erythropoietin receptor (EPOR) and interleukin-2 receptor beta chain (IL-2R beta) belong to the same cytokine receptor superfamily and have highly conserved sequences in their intracellular signaling domain. However, common downstream signaling pathways of these receptors have not been demonstrated. In the present study, we introduced and expressed the murine EPOR in murine IL-2-, IL-3- and IL-5-dependent cell lines and analyzed their growth response to EPO. We found that the expression of EPOR induced EPO dependence in IL-3-dependent BAF-B03 and IL-5-dependent Y16 cells but not in IL-2-dependent CTLL-2 cells, although the EPOR-expressing CTLL-2 cell lines could bind and internalize EPO as efficiently as the BAF-B03-derived cell lines. Additional expression of AIC2B, a common signal transducer for IL-3R, IL-5R and GM-CSFR, made no difference to the EPO responsiveness of the EPOR-expressing CTLL-2 cell lines. These results suggest that the cellular components required for the transduction of EPOR signal and IL-2R signal are at least partially different, and this difference cannot be explained solely by the absence of AIC2B.

Animals↗

PubMed1992

Pharmacokinetic profile of glycyrrhizin in healthy volunteers by a new high-performance liquid chromatographic method.

An improved high-performance liquid chromatographic method was developed for the quantification of glycyrrhizin and its metabolites in human plasma. The improved method was selective and made it possible to determine precisely glycyrrhizin at levels as low as 500 ng/mL. The pharmacokinetic behavior of glycyrrhizin and its metabolites after oral and intravenous administration of glycyrrhizin to normal subjects was investigated. After oral administration of glycyrrhizin (100 mg) to three normal subjects, the major metabolite of glycyrrhizin (glycyrrhetic acid) appeared in plasma (less than 200 ng/mL), but glycyrrhizin was not found. On the other hand, glycyrrhizin was found in urine, and the amount excreted was 1.1-2.5% of the dose. This finding suggests that glycyrrhizin is partly absorbed in the intact form from the gastrointestinal tract. The concentration of glycyrrhizin in plasma after intravenous administration of glycyrrhizin (40, 80, and 120 mg) showed biexponential profiles during the 24-h period after administration of each dose. The glycyrrhizin metabolites, glycyrrhetic acid and glycyrrhetic acid-3-O-glucuronide, were not detected in either plasma or urine. The terminal half-life of glycyrrhizin, the apparent volume of the central compartment, the steady-state distribution volume, and the total body clearance in three dosing experiments were 2.7-4.8 h, 37-64 mL/kg, 59-98 mL/kg, and 16-25 mL/kg/h, respectively. Glycyrrhizin was not detected in plasma after oral administration of the usual therapeutic dose of glycyrrhizin, and no dose dependency of the drug was observed in the dose range of 40-120 mg.

Administration, Oral↗

PubMed1992

Effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on cytotoxicity of PSK-induced peritoneal polymorphonuclear leukocytes (PMNs).

We investigated whether recombinant human granulocyte colony-stimulating factor (rhG-CSF) enhanced the cytotoxicity of PSK-induced polymorphonuclear leukocytes (PMNs) in the peritoneal cavity. Male C3H/He mice, 8- to 10-week-old, received single subcutaneous (s.c.) or intraperitoneal (i.p.) injection of 2.5 micrograms/animal of rhG-CSF at different time points before or after an i.p. administration of PSK. In other experiments, mice were s.c. or i.p. treated with the same dosage of rhG-CSF every day for 7 or 14 consecutive days and i.p. injected with 2.5 mg/animal of PSK on the last day. Peritoneal PMNs were harvested 6 hrs after the administration of PSK and purified to more than 95% by Ficoll-Paque for in vitro cytotoxic assay. In vitro cytotoxic assays with 51Cr labeled MM46 mammary carcinoma cells were added with 5-20 micrograms/ml of Nocardia rubra cell wall skeleton (N-CWS) at the beginning of the assay to augment the cytotoxic activity of PMNs. In vitro addition of rhG-CSF to the assay did not enhance the cytotoxicity of PSK-induced PMNs. However, the cytotoxicity was significantly increased when rhG-CSF was s.c. administered 12 hrs before a PSK injection or 2 or 5 hrs after that. On the other hand, the cytotoxicity was rather weak when mice s.c. or i.p. received consecutive injections of rhG-CSF. This cytotoxicity may be mediated by H2O2, since H2O2 production of PMNs during the cytotoxic assay appears to correlate with the levels of cytotoxicity under suppressed H2O2 generation by catalase or enhanced generation by rhG-CSF. These results suggest that rhG-CSF augments the cytotoxicity of PSK-induced PMNs when administered in vivo timely.

Animals↗

PubMed1992

In vitro augmentation of cytotoxicity by N-CWS in peritoneal polymorphonuclear leukocytes (PMNs) induced by PSK, OK-432 or N-CWS.

Peritoneal polymorphonuclear leukocytes (PMNs) were collected from the peritoneal cavity of C3H/He mice 6 hrs after intraperitoneal (i.p.) injection of 2.5 mg/head of PSK, 1 KE (100 micrograms)/head of OK-432 or 200 micrograms/head of Nocardia rubra cell wall skeleton (N-CWS). Without in vitro stimulation, these PMNs did not show cytotoxicity to syngeneic MM46 mammary carcinoma cells in 51Cr release assay. Cytotoxicity of these PMNs was augmented by the addition of 25 micrograms/ml of N-CWS but not of PSK or OK-432 to cultures for the assay at the beginning of the culture. H2O2 production of PSK-induced PMNs was increased by the in vitro addition of 25 micrograms/ml of N-CWS but not of PSK. These results suggest that PSK as well as OK-432 and N-CWS can induce PMNs capable of responding further to N-CWS as the second stimulant.

Adjuvants, Immunologic↗

PubMed1992

Different origin of leiomyoblastoma by immunohistochemical study.

Leiomyoblastoma has been regarded as a neoplasm of smooth muscle origin. With recent progress in immunohistostaining techniques, many clinicopathological discrepancies have been pointed out about the origin of leiomyoblastoma. It has been claimed that gastrointestinal non-epithelial tumors should be regarded as stromal tumors in order to study their origin. In the present study, we performed various forms of immunohistostaining in seven cases of leiomyoblastoma to determine their origin. One case expressed desmine and muscle specific actin and was considered to be derived from smooth muscle. Four neoplasms expressed X-100 protein (two cases were also NSE positive) and were thought to be derived from the nerve. Two cases were of unknown derivation. These results suggest that the cells of leiomyoblastoma may arise from a primitive to totipotential cell of neural lineages that may anomalously express smooth muscle filaments.

Actins↗

PubMed1992

Metabolism of subcutaneous administered indium arsenide in the hamster.

Indium arsenide (InAs) is partially dissociated in vivo to form inorganic arsenic and indium and excreted into the urine and feces. InAs dissolves slowly over time with deposits at the site of injection. Results of this study demonstrated that the principal metabolite of arsenic in the urine of hamsters was dimethylated arsenic (DMA). Inorganic arsenic and DMA accumulated in the fur, but the concentrations of indium were very low in this matrix. Urine and feces were the principal routes of elimination from the body. Analysis of tissues for arsenic demonstrated as concentrations in the parts per billion range. Results of these studies indicate that InAs is dissociated in vivo with release of both the indium and arsenic moieties to target tissues.

Animals↗

PubMed1992

Exposure to mercury via breast milk in suckling offspring of maternal guinea pigs exposed to mercury vapor after parturition.

Exposure to an exogenous chemical via milk causes superimposition on the body burden that might have already existed in the neonatal organism due to in utero exposure. Such exposure via breast milk is avoidable, although transplacental exposure cannot be avoided at present. In this paper, mercury exposure via breast milk was examined in an animal model. Maternal guinea pigs were shortly exposed to mercury vapor at the mean concentrations of 6-10 mg/m3 immediately after parturition. Newborn guinea pigs were then nursed by the natural mothers. Mercury concentrations in breast milk and tissue samples were determined on d 3, 5, and 10 postpartum. Mercury concentrations in breast milk were slightly lower than plasma mercury concentrations of the maternal guinea pigs over the observation period. However, the decrease in the mercury concentration in breast milk with time was slower than that in maternal plasma. Mercury concentrations in major organs of the neonates were highest in kidney, followed by liver and lung. In brain and whole blood, mercury concentrations were slightly elevated compared with the nonexposed control. Organ distribution of mercury in the suckling neonates indicated that they were exposed via breast milk to inorganic, not elemental, mercury.

Animals↗

PubMed1992

Characterization of a novel aquaretic agent, OPC-31260, as an orally effective, nonpeptide vasopressin V2 receptor antagonist.

1. OPC-31260, a benzazepine derivative, has been studied for its ability to antagonize the binding of arginine vasopressin (AVP) to receptors in rat liver (V1) and kidney (V2) plasma membranes, for antagonism of the antidiuretic action of AVP in alcohol-anaesthetized rats and for diuretic action in conscious normal rats. 2. OPC-31260 caused a competitive displacement of [3H]-AVP binding to both V1 and V2 receptors with IC50 values of 1.2 +/- 0.2 x 10(-6) M and 1.4 +/- 0.2 x 10(-8) M, respectively. 3. OPC-31260 at doses of 10 to 100 micrograms kg-1, i.v., inhibited the antidiuretic action of exogenously administered AVP in water-loaded, alcohol-anaesthetized rats in a dose-dependent manner. OPC-31260 did not exert an antidiuretic activity suggesting that it is not a partial V2 receptor agonist. 4. After oral administration at doses of 1 to 30 mg kg-1 in normal conscious rats, OPC-31260 dose-dependently increased urine flow and decreased urine osmolality. The diuretic action of OPC-31260 was characterized as aquaresis, the mode of diuretic action being different from previously known diuretic agents such as furosemide, hydrochlorothiazide and spironolactone. 5. The results indicate that OPC-31260 is a selective V2 receptor antagonist and behaves as an aquaretic agent. OPC-31260 will be a useful tool in studying the physiological role of AVP and in the treatment of various conditions characterized by water retention.

Administration, Oral↗

PubMed1992

An acute mercuric mercury poisoning: chemical speciation of hair mercury shows a peak of inorganic mercury value.

A woman ingested a dose of sublimate (approximately 0.9 g) in an attempted suicide. She survived and recovered in response to a combination of therapies including chelate (BAL) therapy, plasma exchange, haemodialysis and peritoneal dialysis. Serum inorganic mercury concentration, urinary inorganic mercury excretion and hair inorganic and organic mercury and selenium concentrations, along the length from the scalp to the distal part, were measured. Longitudinal analysis of hair, revealed a peak in inorganic mercury corresponding to the time of mercury ingestion. Organic mercury and selenium in the hair had different patterns of longitudinal variation from that of inorganic mercury. The biological half-life (23.5 d) of serum inorganic mercury levels was in good agreement with values previously reported in the literature.

Adult↗

PubMed1992

Identification and characterization of specific receptors for the LD78 cytokine.

LD78 is a small secreted protein that has a sequence similar to a number of other polypeptides, including murine macrophage inflammatory protein 1 alpha (MIP-1 alpha), interleukin 8 (IL-8), Act-2, monocyte chemoattractant protein 1 (MCP-1), and others. These polypeptides are members of a novel cytokine superfamily that is involved in the inflammatory response, wound healing, hematopoiesis, and tumorigenesis. Specific receptors for purified clonal LD78 protein were measured using four cell lines (HL-60, U937, Jurkat, and MJ). 125I-labeled recombinant LD78 bound most efficiently to U937 cells. We therefore characterized the receptors as being on the surface of U937 cells. Binding reached an equilibrium after incubation for 60 min at 4 degrees C. Scatchard analysis showed that there were two classes of binding sites on U937 cells, high affinity sites (Kd = 5.3 x 10(-9) M) and low affinity sites (Kd = 9.3 x 10(-8) M), with the average number of binding sites per cell being approximately 30,000 and approximately 90,000, respectively. These receptors for LD78 were distinct from the receptors for gamma-IFN and for IL-8. SDS-PAGE analysis of chemically crosslinked 125I-labeled LD78 receptor complexes identified a single band of 52 kDa. The ability to detect specific LD78 receptors should prove valuable in efforts to molecularly clone these receptors and to dissect the biological actions of LD78.

Chemokine CCL3↗

PubMed1991

Selective high-performance liquid chromatographic method for the determination of glycyrrhizin and glycyrrhetic acid-3-O-glucuronide in biological fluids: application of ion-pair extraction and fluorescence labelling agent.

A selective high-performance liquid chromatographic method has been developed for the simultaneous determination of glycyrrhizin and glycyrrhetic acid-3-O-glucuronide in biological fluids of the rat. The procedure is based on the ion-pair formation using tetra-n-amylammonium bromide, extraction with ethyl acetate-n-heptane from the salt-saturated aqueous phase, labelling with 4-bromomethyl-7-methoxycoumarin, followed by chromatographic separation with fluorescence detection. Glycyrrhizin in plasma, bile and urine could be precisely determined in concentrations as low as 1, 1 and 2.5 micrograms/ml, respectively, in a 0.1-ml sample. The equivalent values for the glucuronide were 1, 2.5 and 2.5 micrograms/ml, respectively. The method is applicable in pharmacokinetic studies of glycyrrhizin in small animals.

Animals↗

PubMed1991

OPC-21268, an orally effective, nonpeptide vasopressin V1 receptor antagonist.

An orally effective, nonpeptide, vasopressin V1 receptor antagonist, OPC-21268, has been identified. This compound selectively antagonized binding to the V1 subtype of the vasopressin receptor in a competitive manner. In vivo, the compound acted as a specific antagonist of arginine vasopressin (AVP)-induced vasoconstriction. After oral administration in conscious rats, the compound also antagonized pressor responses to AVP. OPC-21268 can be used to study the physiological role of AVP and may be therapeutically useful in the treatment of hypertension and congestive heart failure.

Administration, Oral↗

PubMed1991

Infection of human CD4+ rabbit cells with HIV-1: the possibility of the rabbit as a model for HIV-1 infection.

Although human T cell surface glycoprotein CD4 is the cellular receptor for human immunodeficiency virus 1 (HIV-1), the introduction of the human CD4 gene into murine cells does not render them susceptible to HIV-1 infection. Here we have established rabbit transfectant cell lines expressing human CD4 on the cell surface and demonstrated that the CD4+ rabbit transfectants could be readily infected by HIV-1 by co-cultivating with a HIV-1-infected human MOLT-4 T cell line (MOLT-4/HIV). Avid syncytia formation was observed upon co-cultivation and the syncytia abundantly produced HIV-1 mature particles, as revealed by electron microscopy. A significant increase of HIV-1 p24 antigen was also detected in the culture supernatant. The syncytia formation was blocked by pretreating the transfectant with anti-human CD4 or by pretreating the MOLT-4/HIV with anti-HIV-1 serum obtained from an infected individual, indicating that the syncytia formed as a result of the interaction of human CD4 on the rabbit transfectant with the HIV-1 envelope protein expressed on MOLT-4/HIV. In contrast, only a very small proportion of the rabbit transfectants expressed HIV-1-specific antigens upon infection with an HIV-1 stock. This may indicate that, although rabbit cells have partially acquired susceptibility to HIV-1 by transfection of human CD4 gene, rabbit cells may further require such a molecule as might be provided by MOLT-4 to become fully susceptible to HIV-1 infection. The possibility of the rabbit as a model for HIV-1 infection is also discussed.

Animals↗

PubMed1991

Rapid serodiagnosis of human mycobacteriosis by ELISA using cord factor (trehalose-6,6'-dimycolate) purified from Mycobacterium tuberculosis as antigen.

IgG antibodies against purified cord factor (trehalose-6,6'-dimycolate, TDM) in sera of 99 patients infected with mycobacteria (42 patients with tuberculosis excreting tubercle bacilli in the sputum, 11 patients with non-tuberculous mycobacteriosis excreting acid-fast bacilli in the sputum, and 46 patients without bacilli in the sputum but diagnosed as having pulmonary tuberculosis by chest X-ray films and physical examination), five patients with lung cancer, and 100 healthy controls which included subjects positive and negative for the tuberculin test were tested by the ELISA with TDM purified from Mycobacterium tuberculosis H37Rv as the antigen. Of the 99 cases of mycobacteriosis, 83 patients (83.8%) had positive results (48 samples from 53 patients, or 90.5%, with bacilli in the sputum, and 35 samples from 46 patients (76%) with tuberculosis diagnosed clinically). The sera of the five patients with lung cancer and the 100 controls all gave negative results. Thus, the sensitivity and specificity were 83.8% and 100%, respectively. ELISA with TDM as the antigen is simple, reproducible, and useful for the rapid serodiagnosis of general mycobacterial infections including tuberculosis, because it does not involve the cultivation of bacteria.

Adult↗

PubMed1991

Increase in tumor necrosis factor alpha- and interleukin-6-secreting cells in peripheral blood mononuclear cells from subjects infected with Mycobacterium tuberculosis.

We detected and quantified tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) from monocytes/macrophages (M phi) in the peripheral blood of subjects from three different population groups, i.e., tuberculin-negative healthy subjects, tuberculin-positive healthy subjects, and patients with active pulmonary tuberculosis. TNF-alpha or IL-6 activity in the culture supernatant of these cells was determined by the cytotoxicity of murine L-929 cells or by enzyme-linked immunosorbent assay, respectively. Detection and enumeration of cells secreting either TNF-alpha or IL-6 were performed by an adaptation of the enzyme-linked immunospot assay. Monocytes/M phi from tuberculin-positive healthy subjects or patients with tuberculosis showed higher TNF-alpha- and IL-6-producing activities than those from tuberculin-negative healthy subjects. The number of TNF-alpha- and IL-6-secreting cells in either lipopolysaccharide- or muramyl dipeptide-stimulated mononuclear cells from tuberculin-positive healthy subjects and patients was significantly higher than that in cells from the tuberculin-negative healthy subjects.

Adult↗

PubMed1991

Metallothionein concentrations and organ retention of mercury in the liver and kidney of the neonatal guinea pig after exposure to mercury vapor.

Neonatal guinea pigs were exposed to mercury vapor on the day of birth, and the following mercury distribution and concentrations of metallothioneins (MTs) in the liver and kidney were observed. In the liver, two hours after exposure, an appreciable amount of mercury accumulated and a substantial portion of this was associated with MTs. During postnatal development, the mercury concentration increased, whereas the hepatic concentration of MTs decreased. The mercury in the soluble fraction of the liver shifted from the region of MTs to the high-molecular-weight region and, finally, the mercury peak in the MT region was not detected. The kidney mercury concentration was high even 2 hr after the exposure and on days 3 and 7 postpartum. The peak concentration was observed on day 3 postpartum. The mean renal concentration of MTs in the mercury-exposed neonates was significantly higher than that of the control at all times observed. The changes in both the mercury level and the concentration of MTs were strongly correlated. Furthermore, most mercury in the soluble fraction was associated with MTs on day 7. These findings indicated enhanced synthesis of MTs in the kidney, but not in the liver, after mercury vapor exposure in the neonatal period, with corresponding elevated copper and zinc concentrations in the kidney.

Administration, Inhalation↗

PubMed1991

Regulatory mechanisms for the expression of a functional beta chain of interleukin 2 receptor on T4 chronic lymphocytic leukemia cells.

Monoclonal antibodies, each recognizing interleukin 2 receptor (IL-2R) alpha, or beta, were used to see the regulatory mechanisms of the expressions on leukemic cells from a patient with T4 chronic lymphocytic leukemia (T4-CLL). Cells from this patient expressed only IL-2R beta, and the expression was enhanced by medium cultivation. IL-1 enhanced the expression of not only IL-2R beta but also IL-2R alpha on the cells. Binding studies using 125I-IL-2 showed the presence of an intermediate receptor (734 sites/cell, Kd = 1.2 nM) and a few high-affinity receptor (172 sites/cell, Kd = 132 pM) on cells cultured with IL-1. IL-2 and IL-1 synergistically promoted the proliferation of the cells, suggesting that the induced IL-2R was functional. In addition, anti-IL-1 antibodies inhibited IL-2R beta expression by cultured cells, suggesting that it was dependent on IL-1 produced by the leukemic cells. These findings suggested that IL-1 might enhance the expression of IL-2R beta in a subset of human T cells, and implied a role of IL-1 in the proliferation of the leukemic T cells.

Aged↗

PubMed1991

[The merit of prescribed exercise using anaerobic threshold for myocardial infarction].

The merit of using anaerobic threshold (AT) for prescribed exercise was evaluated in 55 out-patients with old myocardial infarction (OMI) one to 3 months after the attacks. Comparisons of optimum exercise intensities using 2 methods; either heart rate at AT (ATHR) or heart rate by Karvonen's method (KHR), were conducted. Treadmill stress test was performed in all subjects. ATHR was determined by ramp protocol and KHR by Bruce's protocol. Items measured were AT, peak oxygen consumption (peak VO2), ATHR and KHR. The results were as follows: 1. Mean peak VO2 and AT in patients with OMI were 25.8 +/- 4.3 ml/min/kg and 16.5 +/- 2.1 ml/min/kg, respectively. Mean heart rates were 117.2 +/- 11.0 beats/min at AT and 121.9 +/- 13.0 beats/min by Karvonen's method, respectively. 2. A positive correlation (r = 0.85) was noted between AT and the peak VO2. 3. A positive correlation (r = 0.61) was also noted between the peak VO2 and ATHR. 4. Correlations of KHR with peak VO2 and with ATHR were insignificant. 5. There were 6 patients with ATHR > or = KHR and 15 with ATHR < KHR. There was no significant difference between their clinical backgrounds of 2 groups. It has been thought that with KHR, about 70% of the patients with OMI are overloaded due to excessive exercise intensity. We concluded that exercise training using AT is better and more useful in view of training efficiency and safety.

Anaerobic Threshold↗