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Biomedical subjects

M Ohta

Publications and source records attributed to M Ohta.

At least 901 records · Page 50Linked to original sources
PubMed1989

Treatment of multiple myeloma with carboquone-prednisolone.

18 previously untreated patients with multiple myeloma were entered in a clinical study of a combination chemotherapy, carboquone (CQ) and prednisolone (P) (CQ-P). Response was observed in 44% of patients treated with CQ-P judged by the criteria for response to chemotherapy. The median survival time was 33 months. Serious toxic reactions seldom occurred. The results suggest that the combination of CQ-P has efficacy in the treatment of multiple myeloma and could have a role among primary chemotherapeutic regimens for the disease. Further clinical trials should be conducted to establish a new drug combination in which CQ is included.

Aged↗
PubMed1989

HLA-DP antigens and HTLV-1 antibody status among Japanese with multiple sclerosis: evidence for an increased frequency of HLA-DPw4.

Previously, an association between multiple sclerosis (MS) and HLA-DPw4 has been reported in Scandinavians. In the present study, the distribution of HLA-DP antigens was studied in 34 Japanese MS patients, all of whom fulfilled the criteria for definite MS. HLA-DP typings for DPw1 through w6 and the local specificity, CDP-HEI, were performed using the primed lymphocyte typing (PLT) technique. In addition, the patients were typed for a DR2+, Dw2+/Dw12- related, PLT defined specificity. The distribution of DPw1-w5 in 121 healthy, unrelated Japanese controls were from Nishimura et al., 1984; Nishimura, personal communication). Sera from all 34 patients and 38 controls (both from the HTLV-1 nonendemic, Kyoto region) were examined for the presence of HTLV-1 reacting antibodies by a highly sensitive radioimmuno assay (RIA) using two sources of HTLV-1 antigens, namely total crude protein preparations from disrupted HTLV-1 virions and affinity purified p24 HTLV-1 core proteins. The frequency of DPw4 was significantly increased to 35.3% in Japanese MS patients compared to 16.5% in controls (Relative Risk, RR = 2.8, p = 1.9 x 10(-2)). 41.6% of the MS patients gave clear typing responses with a PLT reagent which recognized a Dw2+ related specificity, which is higher than the frequency of Dw2 (6.8%) in Japanese. Fourteen of the 34 patient sera contrasting to none of the sera from 38 controls contained antibodies of IgG and/or IgM subclasses reacting with the HTLV-1 derived antigens. This difference is highly significant (P less than 1 x 10(-5)).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Chromosomal beta-lactamase of Klebsiella oxytoca, a new class A enzyme that hydrolyzes broad-spectrum beta-lactam antibiotics.

The chromosomally encoded beta-lactamase gene of Klebsiella oxytoca E23004, a strain resistant to cefoperazone and aztreonam, was cloned and expressed in Escherichia coli HB101. The molecular mass and pI of this enzyme were 28 kilodaltons and 7.4, respectively. Although the beta-lactamase of K. oxytoca hydrolyzed many cephalosporins, including broad-spectrum drugs, the nucleotide sequence and deduced amino acid sequence lacked homology with chromosomal class C beta-lactamase genes (ampC) of E. coli or Citrobacter freundii. Rather, about 45% nucleotide sequence homology and 40% deduced amino acid sequence homology were observed between the K. oxytoca beta-lactamase and TEM-1, a class A beta-lactamase which does not efficiently hydrolyze cephalosporins. Values of Km, relative Vmax, and relative Vmax/Km for the K. oxytoca beta-lactamase indicated that the enzyme is a penicillinase but that it can hydrolyze cefoperazone effectively and other broad-spectrum cephems weakly. Hence, the chromosomal beta-lactamase of K. oxytoca E23004 belongs to class A but differences in its amino acid sequence provide a broader spectrum of activity.

Ampicillin↗
PubMed1989

Purification and partial characterization of a type-specific antigen of Rickettsia tsutsugamushi.

A type-specific antigen (54- to 56-kilodalton polypeptide) in the envelope of Rickettsia tsutsugamushi was purified from each of three prototype strains (Gilliam, Karp, and Kato) by a combination of mild anionic detergent treatment, gel filtration, and reverse-phase high-performance liquid chromatography. The purified antigens from the three strains were shown to have similar amino acid compositions: primarily aspartic acid, glutamic acid, and glycine, with lesser amounts of cysteine, methionine, and tyrosine. The N-terminal amino acid sequences of the antigens were 74.3% homologous among the three strains.

Amino Acid Sequence↗
PubMed1989

Phorbol myristate acetate modulates calcium ion-dependent superoxide anion generation induced by a monoclonal antibody raised against polymorphonuclear leukocytes.

We used a monoclonal antibody, YI 51, raised against human polymorphonuclear leukocytes (PMN) to induce superoxide anion (O2-) generation in cells. Although YI 51 alone played only a small part in inducing O2- generation in PMN, the amount of O2- generation induced in 5 X 10(5) PMN was 3.7 to 5.5 nmol/min when F(ab')2 fragments of rabbit anti-mouse immunoglobulin antibody were added as a cross-linking agent. This O2- -inducing activity was high compared with that of wheat germ agglutinin (WGA), insoluble immunoglobulin G immune complexes (IC), or phorbol myristate acetate (PMA). The binding of YI 51 and soluble immunoglobulin G IC to PMN was not reciprocally inhibitory, indicating that YI 51 does not interfere with ligand binding to the Fc receptor-binding site. In the absence of calcium ion (Ca2+), O2- generation induced by YI 51 decreased to 10 to 20% of that in the presence of Ca2+. In contrast, O2- generation in response to WGA, IC, or PMA under Ca2+-free conditions was not affected. When PMN were pretreated with low concentrations of PMA (10(-10) to 10(-9) M), the amount of O2- generation by the cells in response to YI 51 in Ca2+-free buffer was enhanced in a concentration-dependent manner. It also equaled the O2- generated by the cells in buffer containing Ca2+. In cells pretreated with PMA, the amount of O2- induced by WGA was enhanced two- to threefold over that in untreated cells. In contrast, there was no augmentation over untreated cells with stimulation by IC. These results suggest that YI 51, IC, and WGA induce O2- generation in human PMN in different manners.

Animals↗
PubMed1989

Partial deletion of the cloned rfb gene of Escherichia coli O9 results in synthesis of a new O-antigenic lipopolysaccharide.

The rfb gene, involved in the synthesis of the O-specific polysaccharide (a mannose homopolymer) of Escherichia coli O9 lipopolysaccharide (LPS), was cloned in E. coli K-12 strains. The O9-specific polysaccharide covalently linked to the R core of K-12 was extracted from the K-12 strains harboring the O9 rfb gene. All the other genes required for the synthesis of rfe-dependent LPS are therefore considered to be present in the K-12 strains. It was found that bacteria harboring some clones with deletions of the ca. 20-kilobase-pair (kbp) BglII-StuI fragment no longer synthesized the O9-specific polysaccharide. However, bacteria harboring clones del 21, del 22, and del 25, which carry deletions of the 10-kbp PstI-StuI fragment, synthesized an O-specific polysaccharide antigenically distinct from E. coli O9 LPS. Although this new O-specific polysaccharide consisted solely of mannose and the mannose residues were combined only through alpha-1,2 linkage, it was still composed of a repeating oligosaccharide unit, possibly a trisaccharide unit,----2)alpha Man-(1----2)alpha Man-(1----2)alpha Man-(1----. It is therefore likely that this new O-specific polysaccharide was derived from a part of the O9-specific polysaccharide----3)alpha Man-(1----3)alpha Man-(1----2)alpha Man-(1----2)alpha Man-(1----2)alpha Man-(1----and that the deleted part of the clones was responsible for the synthesis of alpha-1,3 linkages of the O9-specific polysaccharide.

Antigens, Bacterial↗
PubMed1989

Responses of vasopressin, atrial natriuretic peptide, and blood pressure to central osmotic stimulation.

To assess whether intracerebroventricular osmoreceptors are involved in vasopressin (AVP) and atrial natriuretic peptide (ANP) release and in the pressor response to centrally administered hypertonic NaCl, artificial cerebrospinal fluid (ACSF) or ACSF made hypertonic by adding 0.2 M NaCl, 0.4 M mannitol, and 0.4 M glucose in isotonic ACSF or 0.4 M urea was infused into the 3rd ventricle of conscious rats. In addition, intravenous infusion of [1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid),2-(O-methyl)tyrosine]AVP (TMeAVP), a V1-AVP antagonist, was given in rats receiving intracerebroventricular infusion of 0.2 M NaCl in isotonic ACSF. Intracerebroventricular 0.2 M NaCl, 0.4 M mannitol, and 0.4 M glucose in isotonic ACSF increased plasma AVP and mean arterial pressure (MAP) without changing heart rate (HR) or plasma ANP. Urea at 0.4 M decreased plasma AVP and ANP with a slight rise in MAP but no change in HR. ACSF alone did not affect plasma AVP, ANP, MAP, or HR. Intravenous TMeAVP attenuated the pressor response to infusion of 0.2 M NaCl in isotonic ACSF, decreased plasma ANP, but did not affect HR. These results indicate that central osmoreceptors are involved in the release of AVP and in the pressor response to centrally administered hypertonic NaCl.

Animals↗
PubMed1989

Gluconeogenesis in perfused livers from dexamethasone-treated chickens.

Gluconeogenesis was studied in hemoglobin-free perfused livers from chickens that had received daily injections of dexamethasone sulfate for 5 days. Dexamethasone increased to approximately 160% the level of plasma glucose and doubled the content of hepatic glycogen in fed chickens. In the isolated perfused livers from chickens starved for 48 h after the last dexamethasone injection, the rates of production of glucose from lactate decreased by approximately 30% and biphasic changes in glucose production from fructose proceeded in parallel with biphasic changes in the production of lactate and pyruvate. Quinolinate had no effect on gluconeogenesis in both groups. NH4Cl markedly inhibited the production of glucose from pyruvate-lactate mixtures in dexamethasone-treated chickens but stimulated in controls. Aminooxyacetate reversed the effects of NH4Cl in dexamethasone-treated chickens. The data presented provide evidence indicating that the reaction of mitochondrial alanine aminotransferase plays an important role in the regulation of the hepatic gluconeogenesis in dexamethasone-treated chickens.

Alanine Transaminase↗
PubMed1989

Aspirin lowers blood pressure in patients with renovascular hypertension.

To clarify the role of renal prostanoid in hyperreninemia and high blood pressure in human renovascular hypertension, we measured prostaglandin E2 and renin activity in renal venous and abdominal aortic plasma before and after the intravenous administration of the cyclooxygenase inhibitor, aspirin DL-lysine. Subjects were six patients with unilateral renovascular hypertension and six with essential hypertension. In patients with renovascular hypertension, prostaglandin E2 concentration in renal venous plasma from the stenotic kidney was 9.25 +/- 1.48 pg/ml, which was significantly higher (p less than 0.01) than the concentration in the renal venous plasma from the normal kidney (4.97 +/- 1.02 pg/ml) or in the aortic plasma (2.59 +/- 0.15 pg/ml). Plasma renin activity was also higher in the renal vein of the stenotic kidney than in the other two sites. The stenotic side/normal side ratio of the renal venous prostaglandin E2 correlated significantly with a renin ratio greater than 1.5 (r = 0.8211, p less than 0.05). Intravenous injection of aspirin DL-lysine (18 mg/kg) 30 minutes later markedly suppressed prostaglandin E2 and renin levels at all sites and clearly lowered arterial blood pressure (mean: from 120 +/- 6 to 110 +/- 5 mm Hg, p less than 0.01). The reduction in blood pressure correlated significantly with the suppression of plasma renin activity in the aorta (p less than 0.05) and in the renal vein of the stenotic kidney (p less than 0.01). Conversely, in patients with essential hypertension, aspirin had little effect on renin levels and increased mean blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Presence of thrombosis-inducing activity in plasma from patients with lung cancer.

Thrombosis-inducing activity (TIA) was detected in the peripheral blood of some patients with advanced lung cancer. When plasma from the patients was given intravenously to mice or to guinea pigs, the animals became immobile within 2 min and died at 3 to 30 min after the injection. Multiple thrombosis was found in the lungs and was considered to be the cause of the death. Thrombosis was not formed and the mice survived when heparin was given intravenously 5 min before the injection of the plasma. This TIA was present in plasma from 13 of 42 patients with lung cancer. On the contrary, only two of 32 with chronic lung diseases and two of 31 healthy control subjects had this activity in the plasma. The coagulation system in the 13 patients was considered to be chronically activated, as revealed by elevation of plasma fibrinogen levels, fibrin degradation product levels, and/or peripheral platelet counts. The TIA shared characteristics with tissue factor in that it was heat labile, nondialyzable through a dialysis membrane with a 10,000 molecular weight exclusion limit, sensitive to phospholipase C treatment, precipitated by 50% ammonium sulfate, and bound to concanavalin-A Sepharose.

Adenocarcinoma↗
PubMed1989

Preoperative examination to detect distant metastasis is not advocated for asymptomatic patients with stages 1 and 2 non-small cell lung cancer. Preoperative examination for lung cancer.

The purpose of the present study was to determine whether all patients with non-small cell lung cancer, clinically defined as stage 1 or 2, should have examinations to determine the presence of distant metastatic (M1) disease. The survival rates of patients who underwent the examinations and those who did not were compared. In all groups, the examinations had in no way positively affected survival. The 33 patients in whom distant recurrence had occurred within 12 months of curative operation, were then evaluated to establish the relationship between the recurrent site and the preoperative examination: negative scans on the examination failed to predict the low incidence of early distant recurrence. Those data suggest that the routine use of radionuclide or CT scans is of no benefit to asymptomatic patients with local, early disease.

Bone Neoplasms↗
PubMed1989

Brain metastases in patients with limited small cell lung cancer achieving complete remission. Correlation with TNM staging.

We reviewed the brain metastases, after treatment, of 45 patients with limited small cell lung cancer who achieved complete remission by radiochemotherapy or curative operation. No patient received prophylactic cranial irradiation. The incidence of subsequent brain metastases was classified according to pretreatment staging as follows: two of 13 (15 percent) patients in stage I; two of ten (20 percent) in stage II; nine of 17 (53 percent) in stage IIIa; and four of five (80 percent) in stage IIIb. The brain metastases occurred from seven to 29 months after the start of treatment, and the median time of the occurrence was 13 months. Of 17 patients who developed brain metastases and who subsequently received cranial irradiation, there were two in whom relapse had occurred at no other site except the brain and who survived 26 and 79 months after the relapse, respectively. These data indicate that not all patients with limited SCLC achieving CR due to treatment necessarily benefit from PCI.

Aged↗
PubMed1989

Plasma active renin concentration in children.

In normal children aged one month to 16 years, the plasma active renin concentration (PARC) was measured with a renin immunoradiometricassay (IRMA) kit, and was compared with plasma renin activity (PRA). The IRMA for renin was found to be independent of the amount of renin substrate and not affected by the dilution of plasma samples, and was therefore proved to be a simple and reliable method. PRA measured in non-diluted plasma samples correlated well with PARC. In the age-related change, PARC in infants was significantly higher than that in older children. In infants, PARC was markedly higher in the crying state than that in the non-crying state. In normal children aged 7 to 11 years, PARC was significantly increased in the upright position compared to the supine position. These findings suggest that a hyperresponse of PARC to acute stress during blood sampling may cause an increase in active renin secretion in infants, and that stimulation by short-term standing may accelerate the activation of inactive renin or the release of active renin.

Adolescent↗
PubMed1989

[Pharmacokinetic analysis in intraperitoneal hyperthermic perfusion using mitomycin C in far-advanced gastric cancer].

Postoperative intraperitoneal hyperthermic perfusion (IPHP) using MMC was performed with marked success on 15 gastric cancer patients with peritoneal dissemination or serosal invasion (first surgery group) and on 5 recurrent gastric cancer patients with ascitic retention (recurrent cancer group), and the MMC concentrations was studied in the perfusate and circulating blood. The perfusate contained MMC 10 micrograms/ml at the onset of IPHP, except one recurrent case of 20 micrograms/ml, and IPHP was performed for 120 minutes except in one case given 20 micrograms/ml of MMC. There was little difference in the hepatorenal functions and perfusate temperatures between the first surgery group and the recurrent cancer group. The drug levels were measured by HPLC method with minimal assay levels of 2 ng/ml. Perfusate drug levels in the first surgery group reduced by half at 12 minutes after the start of IPHP, whereas in the recurrent cancer group, they decreased by half about 60 minutes later. Perfusate drug levels in the first surgery group decreased twice as rapidly as in the recurrent cancer group. The area under the curve (AUC) and average drug levels in the first surgery group were 7,900 micrograms.hr/l and 3.3 micrograms/ml, respectively, and those in the recurrent cancer group were 12,620 micrograms.hr/l and 5.3 micrograms/ml, respectively. On the other hand, the drug levels in peripheral blood were almost the same between the two groups. These data suggest that although recurrent gastric cancer is well suited for IPHP because of high AUC, it is worthwhile performing IPHP combined with surgery for gastric cancer with peritoneal seeding, with due consideration for AUC of 7,900 micrograms.hr/l and the average drug level of 3.3 micrograms/ml.

Adult↗
PubMed1989

Pharmacokinetic analysis in intraperitoneal hyperthermic chemotherapy of far-advanced gastric cancer patients.

The pharmacokinetics of mitomycin C (MMC) has been evaluated in 10 far-advanced gastric cancer patients by means of an intraperitoneal hyperthermic perfusion (IPHP) using MMC to prevent and/or treat peritoneal dissemination. Further, misonidazole (MIS), which was used as a thermosensitizer, also was evaluated. The IPHP was performed for 120 min right after surgical procedure, using a closed-circuit with an inflow perfusate temperature from 46.3 approximately 47.5 degrees C and an outflow temperature of 44.0 approximately 46.0 degrees C. The MMC level in the perfusate was 10 micrograms/ml at the onset of IPHP and thereafter decreased to 1.7 +/- 0.4 micrograms/ml minutes later. The average AUC (area under the curve) in the perfusate was 3.3 micrograms/ml during the IPHP. The MMC level in the peripheral blood was 0.15 +/- 0.04 micrograms/ml 30 min after start of the IPHP and increased to 0.18 +/- 0.05 micrograms/ml at the end of IPHP. Additionally, the MIS level in the peripheral blood was 64.7 +/- 10.3 micrograms/ml 60 min after the IPHP, 60.6 +/- 9.2 micrograms/ml at 120 min, and then decreased to 32.8 +/- 10.3 micrograms/ml at 12 hours after IPHP. The AUC was calculated as being 975 micrograms.hr/ml. Again, the level in the portal vein blood was calculated from the peritoneal permeability and the peripheral blood level of the drug. From data, it was concluded that the perfusate and portal vein blood level of MMC, the peripheral blood level of MIS, as well as the perfusate temperature, are important in providing a favorable, safe, antitumoral treatment.

Adult↗