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Biomedical subjects

J Katahira

Publications and source records attributed to J Katahira.

At least 37 records · Page 2Linked to original sources

Isolation and characterization of a highly divergent HIV-2[GH-2]: generation of an infectious molecular clone and functional analysis of its rev-responsive element in response to primate retrovirus transactivators (Rev and Rex).

A highly divergent HIV-2 designated as HIV-2[GH-2] was obtained from an AIDS-related complex (ARC) patient in Ghana. A full-length molecular clone of this isolate was obtained and a biologically active clone was constructed. Its restriction pattern differed from that of prototype HIV-2[GH-1] in 25 of 35 restriction sites, but was strikingly similar to a previously characterized HIV-2 isolate from a Ghanaian (HIV-2ALT). The conserved integrase region (288-bp fragment) previously displayed 95% identity with that of ALT but 17-20% divergence from the HIV-2 prototype member, and a new distinct subgroup (HIV-2b) of HIV-2 consisting of GH-2 and ALT was postulated (Miura et al. 1991.) These isolates, however, were biologically distinguishable from each other by its replication capacity in a monocyte line, U937, in which GH-2 could not grow but ALT grew well. In addition, the nucleotide sequence of the LTR of this new isolate displays 21% divergence from that of prototype HIV-2[GH-1], but the core enhancer, Sp1 binding sites and TATA box were conserved. Although the 3' half of the env gene sequence which is deleted in HIV-2ALT clone showed 27% diversity from the prototype, functional differences in the rev-responsive element were not observed.

Cloning, Molecular↗

Efficacy of the glyceryl trinitrate transdermal therapeutic system in a dog model of heart failure.

The efficacy of a controlled-release topical dosage form of glyceryl trinitrate (Nitroglycerin Transdermal Therapeutic System, Nitroderm TTS, NTG-TTS; CAS 55-63-0) was studied in the experimental model of congestive heart failure in beagles. NTG-TTS suppressed the increase in left ventricular end-diastolic and central venous pressure, and total peripheral resistance resulting from propranolol, dextran and l-phenylephrine infusion. NTG-TTS antagonized the decrease in cardiac output in this model. These effects of NTG-TTS on congestive heart failure were presumably attributable to the reduction of pre-load, together with direct vasodilation of the peripheral arteries.

Administration, Cutaneous↗

Effect of benazepril hydrochloride on cardiac hypertrophy in spontaneously hypertensive rats.

To study the effects of a novel angiotensin I converting enzyme inhibitor (ACEI) on hypertension-induced cardiac hypertrophy, benazepril hydrochloride (CGS 14824 A, CAS 86541-74-4) at the dose of 3 and 10 mg/kg/d p.o. was administered to spontaneously hypertensive rats from 4 to 16 weeks of age. In addition to suppression of developing blood pressure, benazepril hydrochloride reduced both the wet weights of whole heart and left ventricle dose-dependently and significantly. Benazepril hydrochloride had no effect on hydroxyproline concentration and content or protein concentration in the left ventricle, whereas is reduced the total protein content dose-dependently. Serum ACE activity was significantly reduced at 10 mg/kg/d of benazepril hydrochloride, but renin activity, aldosterone and noradrenaline concentration in serum were not changed. From the microscopic findings of the left ventricle, benazepril hydrochloride reduced the myocardial hypertrophy significantly. From these results, benazepril hydrochloride seems to suppress the increase in volume load by acting through the renin-angiotensin-aldosterone system, and dose not seem to cause a significant reflex of catecholamine which often occurs with peripheral vessels dilation. Thus, benazepril hydrochloride may be expected to suppress cardiac hypertrophy in patients with hypertension.

Aldosterone↗

[Four cases of adult Listeria monocytogenes infection in the last 5 years--hepatic necrotic foci in the adult septic case].

We have reported on the clinical courses of 4 cases of adult Listeria monocytogenes (Lm) infection, and the autopsy findings of 2 cases, those we have observed over the past 5 years. They were 2 cases of meningitis, 1 case of meningitis and sepsis and 1 case of sepsis. These 4 cases had CML, neoplastic angioendotheliosis, SLE and post-renal transplant condition, as their underlying diseases, and all were receiving immunosuppressive therapy. One meningitis patient who recovered showed mild liver dysfunction during her clinical course. The other 3 patients who died had jaundice at the time of onset and severe liver dysfunction. The 2 cases those were autopsied were the sepsis cases. The one with an acute course and hepatic failure showed multiple miliary necrotic foci in the liver, where the presence of Lm in the cells could be verified. The other autopsy case, which had received adequate antibiotic therapy and the Lm infection had been cured, showed no necrotic foci in the liver. The case that had necrotic foci in the liver was the first such adult case in Japan. We have discussed the hepatic Lm infection in adult compromised hosts, which conventionally has not been considered a serious problem.

Aged↗

Protective effect of piperacillin against the nephrotoxicity of cisplatin in rats.

The protective effect of piperacillin against the nephrotoxicity of cisplatin was compared with that of fosfomycin in Fischer 344 rats. Blood urea nitrogen, serum creatinine, and morphological changes were evaluated as the renal toxicological parameters. Rats receiving 2 mg of cisplatin per kg of body weight for 5 days showed significant (P less than 0.01 by multiple-comparison test) elevation of blood urea nitrogen and serum creatinine concentrations compared with rats receiving saline alone and also exhibited development of cell lesions in the pars recta of the tubules in the outer stripe of the outer medulla. However, piperacillin (250 and 1,000 mg/kg) significantly (P less than 0.01 by multiple-comparison test) reduced these toxicological parameters in comparison with results for cisplatin alone. The protective effect of piperacillin was superior to that of fosfomycin, although platinum levels in the kidney were higher with the combination of cisplatin and piperacillin than with cisplatin plus fosfomycin. Although the nephrotoxicity of cisplatin was also reduced when cisplatin was administered concomitantly with sodium chloride in mole-equivalents to 250 and 1,000 mg of piperacillin per kg, its protective effect was less than that of the corresponding piperacillin dose. These results suggest that piperacillin may have a role as a protective agent against the nephrotoxicity of cisplatin.

Animals↗

Effect of recombinant hemopoietic growth factors on human megakaryocyte colony formation in serum-free cultures.

The effects of recombinant hemopoietic factors on the clonal growth of human megakaryocyte progenitors were explored using serum-free cultures of nonadherent and T-cell-depleted marrow cells. Recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) supported megakaryocyte colony formation in a dose-dependent manner, the activity being lower than that of recombinant interleukin 3 (rIL-3). Recombinant IL-3 and rGM-CSF acted synergistically on megakaryocyte colony formation when rGM-CSF was added to cultures containing suboptimal concentrations of rIL-3. However, the number and size of colonies did not increase with rGM-CSF when cultures were plated with an optimal dose of rIL-3. Recombinant erythropoietin (rEpo) by itself did not stimulate the growth of megakaryocyte progenitors. Recombinant Epo did, however, produce a significant increase in the number and size of megakaryocyte colonies in the presence of rIL-3 or rGM-CSF. Other factors, including recombinant granulocyte colony-stimulating factor, recombinant interleukin 1 alpha, recombinant interleukin 4, and recombinant interleukin 6 showed no capacity to generate or enhance megakaryocyte colony formation when added to cultures alone or in combination with varying concentrations of rIL-3. These results show that rIL-3, rGM-CSF, and rEpo affect human megakaryocytopoiesis by themselves or by interacting with each other.

Blood Physiological Phenomena↗

Production of monoclonal antibody to characterize the antigen of Paragonimus westermani.

We produced monoclonal antibodies against the adult antigen of Paragonimus westermani to investigate the expression of the stage-specific antigen of adult flukes. Two hybridoma cell lines, A1-2 and A4-1, were established. A1-2 reacted specifically only with the adult antigen in an enzyme-linked immunosorbent assay (ELISA), whereas A4-1 reacted with both adult and larval antigens. By immunoblotting analysis, A1-2 was found to react with four bands with molecular weights of 35,000, 17,000, 15,500, and 12,500 in the adult antigen but with none in the larval antigen. A4-1 was found to bind to the band of 27,000 daltons in the adult antigen as well as those of 28,000 and 26,000 daltons in the larval antigen. By immunohistochemical methods, a positive reaction was observed only in the parenchymal tissues of the adult flukes with A1-2. A4-1 reacted with the substance that located on the gut epithelium and in the luminal contents of both the adult and larval flukes. These results indicate that the adult P. westermani possesses an antigen or antigenic determinant specific to the adult stage, as well as that common to both the larval and adult stages.

Animals↗

Protective effect of piperacillin against nephrotoxicity of cephaloridine and gentamicin in animals.

The protective effect of piperacillin against the nephrotoxicity of cephaloridine and gentamicin was examined in experimental animals. In rabbits, piperacillin was infused at a dose of 1 mg/kg (body weight) per min over 225 min and cephaloridine (300 mg/kg) was intravenously administered as a bolus 45 min after the start of a drip infusion. Blood urea nitrogen, serum creatinine, and N-acetyl-beta-D-glucosaminidase (NAG) in urine were measured as the renal toxicological parameters before and 24 h after cephaloridine dosing. Although the single administration of cephaloridine significantly elevated these parameters, the elevation was prevented by the concomitant administration of piperacillin. The protective effect of piperacillin was superior to those of cephalothin and fosfomycin. In rats, piperacillin (1,000 mg/kg) was intravenously administered and immediately followed by the intramuscular administration of gentamicin (100 mg/kg) every 24 h for 5 days. When piperacillin was concomitantly administered with gentamicin, the elevations of blood urea nitrogen, serum creatinine, and urinary NAG were significantly lower than when gentamicin was given alone. The concomitant administration of piperacillin resulted in a significant protective effect against the nephrotoxicity of cephaloridine in rabbits and of gentamicin in rats. Histopathological observation also supported the protective effect of piperacillin. The protective mechanism of piperacillin might be the inhibition of transport from the peritubular side to tubular cells for cephaloridine and from both the peritubular and luminal sides for gentamicin.

Animals↗

Clonal growth of human megakaryocyte progenitors in serum-free cultures: effect of recombinant human interleukin 3.

Human megakaryocyte colony formation was observed in serum-free agar cultures with a medium containing deionized bovine serum albumin, iron-saturated transferrin, 2-mercaptoethanol, and recombinant human interleukin 3 (IL-3). Megakaryocyte colonies were identified in situ by the alkaline phosphatase anti-alkaline phosphatase technique, using monoclonal antibody against platelet glycoprotein IIb/IIIa. Colony numbers reached a peak at day 14, with a mean of 47 megakaryocyte colonies (range 23-104) per 2 x 10(5) bone marrow mononuclear cells. Recombinant human IL-3 stimulated the growth of megakaryocyte progenitors. Similar results were obtained using nonadherent, T-cell-depleted mononuclear cells. These findings suggest that IL-3 stimulates the growth of megakaryocyte progenitors directly without activation of accessory cells, or the requirement of factors present in the serum or plasma. This serum-free culture system may be useful for studying the effects of purified natural and recombinant biological regulators on human megakaryocyte progenitors.

Colony-Forming Units Assay↗

Improvement of culture conditions for human megakaryocytic and pluripotent progenitor cells by low oxygen tension.

The effect of low oxygen tension on the growth of human hemopoietic progenitor cells in bone marrow was investigated using the semisolid methylcellulose colony assay. The clonal growth of granulocyte-macrophage progenitors (CFU-gm), early (BFU-e) and late (CFU-e) erythroid progenitors, megakaryocyte progenitors (CFU-meg) and pluripotent progenitors (CFU-mix) improved more markedly incubation at the low oxygen tension (5%) than in conventional air (20%). The thiol compound 2-mercaptoethanol had a strong additive effect on colony growth in conventional air, but little or no effect in the low oxygen tension. These results suggest that enhancement of colony growth in the low oxygen tension may be due to a decrease in the production of oxygen intermediates.

Bone Marrow Cells↗

Paroxysmal nocturnal hemoglobinuria terminating in TdT-positive acute leukemia.

A case of paroxysmal nocturnal hemoglobinuria (PNH) which developed terminal transferase (TdT)-positive leukemia 5 years after the diagnosis of PNH was studied. Most of the leukemic cells were suggestively lymphoid by cytochemistry and electron microscopy, and TdT-positive by immunofluorescence studies. The development of acute lymphoblastic leukemia during the course of PNH suggests that in PNH the clonal abnormality may involve lymphoid cells as well as myeloid cells, thus raising the possibility of the disease being a disorder of the pluripotential stem cell.

Aged↗