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Biomedical subjects

T Hara

Publications and source records attributed to T Hara.

At least 973 records · Page 54Linked to original sources
PubMed1986

Factor VIII concentrate-responsive thrombocytopenia, hemolytic anemia, and nephropathy. Evidence that factor VIII:von Willebrand factor is involved in its pathogenesis.

A 4-year-old Japanese girl had a congenital disorder that was characterized by recurrent thrombocytopenia, hemolytic anemia, hematuria, and proteinuria, which were repeatedly improved by the infusion of factor VIII concentrate. She developed the similar symptoms within 1 h after 1-desamino-8-D-arginine vasopressin (DDAVP) administration. Coagulation studies 30 and 60 min after DDAVP infusion showed a disappearance of large factor VIII:von Willebrand factor (VIII:vWF) multimers, which was the same abnormality that was observed at acute episodes. There were no significant changes in the plasma levels of 6-keto-prostaglandin F1 alpha and thromboxane B2 before and after DDAVP infusion. These results provide further support that VIII:vWF is directly involved in the pathogenesis of this congenital disorder.

Anemia, Hemolytic↗
PubMed1986

In vitro activity of ME1401, a new antifungal agent.

The in vitro antifungal activity of ME1401, a potential topical antifungal agent, was compared with that of haloprogin, clotrimazole, miconazole, tolnaftate, and ciclopirox olamine by using an agar dilution procedure. ME1401 showed a broad antifungal spectrum and inhibited all of the 428 strains of 52 species of pathogenic yeasts and filamentous fungi tested at concentrations ranging from 0.01 to 12.5 micrograms/ml. In general, the activity of ME1401 was comparable or superior to that of clotrimazole and was greater than that of haloprogin and the other reference drugs under the conditions used. Only tolnaftate was superior to ME1401 in its activity against clinical isolates of Trichophyton rubrum. ME1401 showed no cross-resistance with any of the reference drugs and exhibited potent fungicidal activity.

Antifungal Agents↗
PubMed1986

Conjugate pendular nystagmus evoked by accommodative vergence.

Conjugate pendular nystagmus evoked by accommodative vergence in a healthy 18-year-old girl is described. This is clinically demonstrated to be induced by accommodative convergence, and not related to fusional convergence. The lack of neurological or ophthalmic abnormalities supports the classification of a 'congenital' type of this rare phenomenon. A differential diagnosis is also discussed.

Accommodation, Ocular↗
PubMed1986

Defective expression of T cell-associated glycoprotein in severe combined immunodeficiency.

A T cell surface membrane-associated glycoprotein, Tp40 (40,000 mol wt), also designated as CD-7, was not expressed by the T cells of a patient with severe combined immunodeficiency. In addition to this abnormality, T cell proliferative responses to mitogens were defective and the IL-2 receptor expression was deficient on the patient's T lymphocytes. However, his T cells were found to provide help for the differentiation of normal B cells to Ig-secreting cells. Abundant circulating B cells were detected. These B cells proliferated normally in the presence of anti-mu antibodies and B cell growth factors, but did not differentiate into antibody-secreting cells when provided with the help of normal T cells. In addition, his activated B cells did not proliferate to IL-2 even though IL-2 receptors were expressed. A successful allogeneic histocompatible bone marrow transplantation resulting in T cell engraftment corrected both the T and B cell immunodeficiencies. These findings support the hypothesis that the Tp40 deficiency present in this patient is related to a defect of the T cell precursors, and that Tp40 plays important roles not only essential to T cell interactions but also to certain aspects of T-B cell interaction during the early lymphoid development.

Antibodies, Monoclonal↗
PubMed1986

[Anti-tumor activity of an anti-human alpha-fetoprotein antibody-human serum albumin-mitomycin C conjugate against human yolk sac tumor maintained in vitro and in nude mice in vivo].

The anti-cancer drug, mitomycin C (MMC), was conjugated to an affinity-purified horse antibody to human alpha-fetoprotein (aAFP) via purified human serum albumin (HSA) as an intermediate carrier. The conjugate (aAFP immunoglobulin (IgG): HSA: MMC, molar ratio 1: 1.10:29.8) was 21 or 38 times as cytotoxic as free MMC or PBS at the MMC concentration of 100 ng/ml, respectively, against alpha-fetoprotein-producing human yolk sac tumor in vitro. The in vivo effects of the conjugate and various controls were also tested against human yolk sac tumor growing in nude mice. The conjugate over a total of 6 injections retarded the initial tumor growth at the concentration of MMC, containing equivalent amounts of 2 micrograms/mouse (0.1 mg/kg)/injection in the conjugate, whereas free MMC and normal horse IgG-HSA-MMC showed only slight inhibitory effects alone at non-toxic levels. These results suggest that the specific antibody-conjugate was considerably more effective than free MMC against the tumor maintained in nude mice as well as in vitro cultures.

Animals↗
PubMed1986

Effector mechanism in antitumor activity of monoclonal antibodies produced against an ascitic mouse mammary tumor.

Therapeutic effects of monoclonal antibodies with different immunoglobulin classes, detecting the same antigenic determinant of tumor specific antigen expressed on ascitic mouse mammary tumor MM46, were examined. With i.v. administration of gamma 2a, gamma 2b, or gamma 1 antibody we were able to keep a significant proportion of mice tumor free against i.p. inoculation of 5 X 10(4) MM46 cells with doses as small as 0.5 micrograms, but with administration of mu, gamma 3, or alpha antibody we were not able to keep mice tumor free with doses up to 5 micrograms. With 200 micrograms of antibody, however, an antitumor effect was observed even with mu or gamma 3 antibody, although alpha antibody still showed no effect at all. The therapeutic effect of gamma 2a was further examined in mice challenged with an increasing dose of tumor cells, and a significant effect was demonstrated against 1 X 10(6) cells with 200 micrograms of antibody but not against 5 X 10(6) cells. To assess the effector cells in antitumor activity of antibody in vivo, a histological examination of the tumor cells treated with each class of antibody was carried out. The tumor treated by gamma 2a antibody revealed a remarkable cell infiltration consisting predominantly of mononuclear cells, whereas those treated by mu, gamma 3, or alpha antibody did not. The tumor cells treated by gamma 1 or gamma 2b antibody showed a moderate cellular reaction. Next, a Winn assay was carried out in athymic C3H/HeN-nu/nu mice using gamma 2a antibody. A significant antitumor effect was observed even in those mice, indicating that T-cells are not predominant effector cells. The role of macrophages was studied in mice treated with two macrophage toxic agents, carrageenan and silica particles. These agents were shown to reduce the antitumor effect of gamma 2a antibody in both Winn assays and therapeutic experiments. Thus, histological examination and the blocking effect of macrophage toxic agents suggested the participation of host macrophages as effector cells in antibody-mediated tumor cell suppression in vivo.

Animals↗
PubMed1986

[Fundamental and clinical studies of imipenem/cilastatin sodium in the field of obstetrics and gynecology].

Fundamental and clinical studies of a new carbapenem antibiotic, imipenem/cilastatin sodium (MK-0787/MK-0791), were carried out to evaluate the drug in treating infections of the female genital organs. The following results were obtained: In 4 patients undergoing hysterectomy, the penetration of MK-0787 and MK-0791 into female genital organ tissues was studied following a 30-minute intravenous drip infusion of MK-0787/MK-0791 500 mg/500 mg. Plasma levels of MK-0787 and MK-0791 in cubital venous blood following the drip infusion peaked at 0 minute with values of 51.2 micrograms/ml and 61.9 micrograms/ml, respectively, then decreased to 1.9 micrograms/ml and 0.7 microgram/ml, respectively, at 201 minutes. MK-0787 penetrated readily to female genital organ tissues and levels of the drug exceeded 0.5 approximately 1.9 micrograms/g in various organ tissues at 201 minutes following an intravenous drip infusion of 500 mg/500 mg of MK-0787/MK-0791. Clinically, MK-0787/MK-0791 was used for the treatment of obstetrical and gynecological infections at a dosage of 500 mg/500 mg twice daily by intravenous drip infusion. Clinical effects of MK-0787/MK-0791 were analyzed in 22 patients, including 9 patients with intrauterine infections, 7 with intrapelvic infections, 5 with adnexitis, and 1 with an external genital infection. Excellent responses were seen in 5 patients (22.7%), good responses in 15 (68.2%), and poor responses in 2 (9.1%). The efficacy ratio was 90.9%. After the treatment, 15 out of 18 isolates were eradicated for an 83.3% eradication rate. All strains of S. epidermidis (2 strains), Eubacterium lentum (1 strain), Peptococcus sp. (1 strain), beta-Streptococcus (1 strain), Gram-positive rods (2 strains), Enterobacter cloacae (1 strain), Bacteroides bivius (1 strain), Pseudomonas sp. (1 strain), Pseudomonas cepacia (1 strain) and Gram-negative rods (1 strain) were eradicated by the MK-0787/MK-0791 treatment. The safety of the drug was analyzed in 22 patients, effects occurred in 3 (13.6%). Among those 3 patients, diarrhea occurred in 1 patient, rash in another and nausea and vomiting in yet another. One patient had an increased BUN after the MK-0787/MK-0791 treatment. In the other 21 patients, no abnormalities in creatinine, GOT, GPT, or T. Bil. values were observed. It may be concluded that MK-0787/MK-0791 is useful for the treatment of obstetrical and gynecological infections.

Adolescent↗
PubMed1986

[Toxicological studies on isepamicin (HAPA-B). I. Acute toxicity test in the mouse, rat and dog].

Acute toxicity of isepamicin (HAPA-B), a new aminoglycoside antibiotic, in mice, rats and dogs was examined in comparison with amikacin (AMK) and gentamicin (GM). Intravenous LD50 values of HAPA-B were 234 mg/kg in male and 236 mg/kg in female for mice, 489 mg/kg in male and 476 mg/kg in female for rats and 720-864 mg/kg for dogs. Those of AMK were 183 mg/kg in male and 181 mg/kg in female for mice, 420 mg/kg in male and 417 mg/kg in female for rats. Those of GM were 50 mg/kg in male and 47 mg/kg in female for mice, 119 mg/kg in male and 124 mg/kg in female for rats. Intraperitoneal LD50 values of HAPA-B were 2,244 mg/kg in male and 2,272 mg/kg in female for mice, 1,664 mg/kg in male and 1,591 mg/kg in female for rats. Intramuscular LD50 values of HAPA-B were 2,508 mg/kg in male and 2,632 mg/kg in female for mice, 2,088 mg/kg in male and 2,111 mg/kg in female for rats and greater than 1,800 mg/kg for dogs. Those of AMK were 1,247 mg/kg in male and 1,334 mg/kg in female for mice, 2,324 mg/kg in male and 2,244 mg/kg in female for rats. Those of GM were 359 mg/kg in male and 360 mg/kg in female for mice, 559 mg/kg in male and 557 mg/kg in female for rats. Subcutaneous LD50 values of HAPA-B were 3,321 mg/kg in male and 3,320 mg/kg in female for mice, 3,451 mg/kg in male and 3,392 mg/kg in female for rats. Oral LD50 values of HAPA-B were more than 5,000 mg/kg in mice and rats. Ataxia, acratia, dyspnea and convulsions were observed following administration by all routes, except for oral route, of all drugs in mice, rats and dogs. The cause of early death was due to respiratory paralysis which is the typical acute toxic sign of aminoglycoside antibiotics, and that of late death was due to renal injuries. BUN and creatinine values of surviving dogs after day 14 increased after administration by either intravenous or intramuscular routes. Disintegration, necrosis and calcification of epithelial cells of the proximal convoluted tubuli were observed in rats which died during the course of the study, and atrophy, dilatation and eosinophilic degeneration in epithelial cells of the proximal convoluted tubuli and thickening of Bowman's capsule were observed in surviving dogs.

Administration, Oral↗
PubMed1986

Similarities between rat liver mitochondrial and cytosolic glutathione reductases and their apoenzyme accumulation in riboflavin deficiency.

Glutathione reductase has been purified 5,500-fold from rat liver mitochondrial matrix in a yield of 30%. The mitochondrial enzyme was immunochemically indistinguishable from that of the cytosol and the subunit molecular weight was apparently similar to that of the cytosolic enzyme, that is, 50,000 daltons. The optimum pH and kinetic properties investigated were not significantly different from those of the cytosolic enzyme. When rats were fed a riboflavin-deficient diet, the enzyme activity in the mitochondria decreased to a greater extent than that in the cytosol, and greater accumulation of apo-enzyme in the former than that in the latter was confirmed by the amount of immunoprecipitable protein, activation by FAD addition in vitro, and the enzyme activity recovery after injection of riboflavin, into riboflavin-deficient rats.

Animals↗
PubMed1985

Human T cell activation. II. A new activation pathway used by a major T cell population via a disulfide-bonded dimer of a 44 kilodalton polypeptide (9.3 antigen).

In previous studies (17-21), monoclonal antibody (mAb) 9.3 has been shown to react with a major population of human T cells, which include T4+ helper/inducer T cells and T8+ cytotoxic T cells. In this investigation, mAb 9.3 was shown to precipitate a disulfide-bonded dimer of a 44 kD polypeptide. Comodulation experiments showed that this molecule is not linked to T3/Ti or T11 antigens. mAb 9.3 was capable of inducing T cell proliferation in the presence of 12-o-tetradecanoyl phorbol-13-acetate (TPA). This effect was monocyte-independent. T cell activation with mAb 9.3 and TPA was associated with increases in interleukin 2(IL-2) receptor expression and IL-2 secretion. mAb 9.3 did not activate T cells, even with the addition of IL-1 or IL-2. Modulation of the T3 complex did not abolish mAb 9.3-induced T cell proliferation in the presence of TPA. These results suggest that the 9.3 antigen may serve as a receptor for an activation pathway restricted to a T cell subset.

Antibodies, Monoclonal↗
PubMed1985

Human T cell activation. I. Monocyte-independent activation and proliferation induced by anti-T3 monoclonal antibodies in the presence of tumor promoter 12-o-tetradecanoyl phorbol-13 acetate.

Three monoclonal antibodies (mAb), of IgG1, IgG2a, and IgM isotypes, raised against the T3 complex, were used to probe the activation of human T cells. The IgM antibody 235 was not mitogenic for peripheral blood mononuclear cells (PMC). It efficiently blocked the proliferation of PMC induced by T cell mitogens, alloantigens, and soluble antigens. The other two antibodies were mitogenic, and behaved similarly to Leu 4 and OKT3, respectively. In T cell preparations with less than 0.1% monocytes (as assayed by nonspecific esterase staining), all three mAb were not mitogenic. They failed to induce either interleukin 2 (IL-2) receptor expression or IL-2 secretion. Addition of IL-1 failed to collaborate with anti-T3 mAb to induce these T cells to proliferate, but IL-2 enhanced T cell proliferation slightly. Monocyte-depleted T cells, however, proliferated in response to all three anti-T3 mAb, when TPA was added, in a dose-dependent manner. TPA induced a low level of IL-2 receptor expression in monocyte-depleted T cells, without inducing IL-2 secretion. Anti-T3 plus TPA induced a marked enhancement in both quantity and intensity of IL-2 receptor expression. IL-2 secretion was also detected. These results indicate that anti-T3 IgM can deliver an inductive signal despite its blockage of T cell proliferation, and that two signals are necessary and perhaps sufficient to induce human T cell activation and proliferation.

Animals↗
PubMed1985

Synthesis of pyruvate-1-11C as a radiopharmaceutical for tumor imaging.

Pyruvate-1-11C was prepared enzymatically by the exchange reaction of 11CO2 with the carboxyl group of pyruvic acid using pyruvate-ferredoxin oxidoreductase from Clostridium butyricum. 11C-Labeled pyruvate was purified by sublimation in specially made glassware. The radiochemical yield of pure pyruvate-1-11C was 80% 35 min after the end of bombardment. The distribution of 11C in tumor-bearing rabbits after an i.v. injection of pyruvate-1-11C was observed using a gamma camera. In contrast to normal organs, the tumor was positively visualized. We also conducted a number of successful clinical studies. A case of brain tumor which exhibited a positive image on positron-emission tomography (PET) using pyruvate-1-11C is presented.

Animals↗
PubMed1985

Cytostasis of tumor cell lines by promyelocytic leukemia cell line HL60 differentiated to granulocyte lineage.

The human promyelocytic leukemia cell line HL60, when cultured in medium containing dimethyl sulfoxide (DMSO) or granulocyte colony-stimulating factor (G-CSF), stopped dividing and differentiated into cells with granulocyte characteristics. We found that differentiated HL60 cells have no detectable cytolytic activity against cultured human bladder cell line (T24 cell), as measured by release of (3H) thymidine, or against K562 cells, as measured by release of chromium-51. Differentiated HL60 cells inhibited incorporation of (3H) thymidine into the DNA of adherent T24 cells. Decreased incorporation was not caused by detachment of the target T24 cells from the culture wells. The degree of cytostasis was dependent on the E/T ratio, with a 70%-80% inhibition usually reached at the E/T ratio of 200:1. A wide variety of target cells was also shown to be sensitive to differentiated HL60 cell-mediated cytostasis.

Cell Differentiation↗
PubMed1985

High doses of gamma globulin and methylprednisolone therapy for idiopathic thrombocytopenic purpura in children.

In four children with chronic idiopathic thrombocytopenic purpura (ITP), high doses of gamma globulin or methylprednisolone were effective in increasing platelet counts transiently, yet there was no quantitative relationship between the platelet responses to these two therapies. This finding suggests a qualitative difference in the mechanisms of increasing platelets by the two drugs. High doses of gamma globulin and methylprednisolone showed a synergistic effect on the initial and maximal platelet responses, suggesting an intensification of the effect of gamma globulin by methylprednisolone. This combination therapy should be clinically useful, particularly in the control of acute haemorrhage or in preparations for emergency surgery.

Child↗