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Biomedical subjects

S Harada

Publications and source records attributed to S Harada.

At least 469 records · Page 26Linked to original sources
PubMed1989

Lactivicin, a naturally occurring non-beta-lactam antibiotic having beta-lactam-like action: biological activities and mode of action.

Lactivicin is moderately active against a wide range of Gram-negative bacteria and highly active against Gram-positive bacteria. It shows various biological activities commonly observed with beta-lactam antibiotics, such as higher activity against beta-lactam hypersensitive mutants than against their parents, sensitivity to beta-lactamases, inhibitory activity against beta-lactamases and ability to induce beta-lactamase activity. The primary lethal target of lactivicin in Escherichia coli is highly likely to be penicillin-binding protein (PBP) 1; lactivicin strongly lysed E. coli cells with induction of spheroplasts at its MIC, and showed high affinity for PBPs 1A and 1B. At concentrations above x 5 MIC, however, lactivicin dominantly exhibited secondary antibacterial action possibly owing to inhibition of crucial SH proteins engaged in the fundamental membrane functions. In contrast, against Bacillus subtilis, lactivicin showed the typical beta-lactam action under a wide range of concentrations. It showed high affinity for PBPs 1, 2 and 4, the possible lethal targets of beta-lactam antibiotics in this organism. In conclusion, lactivicin is the first non-beta-lactam antibiotic showing beta-lactam action through binding to PBPs.

Anti-Bacterial Agents↗
PubMed1989

[Flowcytometric analysis of lymphocytes proliferated in vitro by PPD].

The present study was undertaken to do phenotype determination of in vitro proliferating lymphocytes by PPD stimulation using combination of monoclonal antibodies and flow-cytometry. The results obtained were as follows: 1) PPD induced a significant proliferation of activated T cell subsets (Leu4+DR+ cells, IL2-R+Leu3+ cells). 2) PPD also induced a significant increase in Pan T cells (Leu4+) and helper T cells (Leu3+8-). Taken together, these results indicated that PPD induced proliferating lymphocytes belong predominantly to helper T cell subset. 3) The numbers of inducer T cells (Leu3+8+), suppressor T cells (Leu2+15+) and cytotoxic T cells (Leu2+15-) were not influenced by PPD-stimulation. 4) However, PPD induced a smaller, but significant proliferation of IL2-R+Leu2+ cells. 5) The number of B cells (Leu4-DR+) tended to increase slightly after PPD-stimulation.

Adult↗
PubMed1989

A case of simultaneous bilateral herpetic epithelial keratitis.

The patient, a 56-year-old man, presented with dendritic keratitis in the right eye and geographic keratitis in the left, with decreased corneal sensation in both eyes. The virus isolated from both eyes was identified as herpes simplex virus (HSV-1) by the indirect immunofluorescent method using anti-HSV-1 monoclonal antibody. Antibody tests of paired sera suggested that the epithelial lesions were not primary but recurrent. No significant difference was observed in DNA cleavage patterns between the virus isolates obtained bilaterally.

Cell Division↗
PubMed1989

[Family study on mitochondrial DNA polymorphism].

Mitochondrial DNA restriction fragment length polymorphisms (mtDNA RFLPs) were surveyed among 19 Japanese families with 67 individuals including twins. A mother and children, and siblings of each family showed the same pattern of mtDNA RFLPs. Samples from Japanese war orphans remained in China and their probable relatives were also surveyed and one pair indicating a high probability to be siblings using other genetic markers possessed the same variant of mtDNA. Moreover mtDNA RFLPs was applied for maternity test among two families. The data suggested that parents mistook their children for each other at birth.

Adult↗
PubMed1989

In vitro immunoglobulin production by peripheral blood mononuclear cells as a prognostic factor in IgA nephropathy.

To determine whether immune system disorders are involved in the exacerbation of IgA nephropathy, the immunoglobulin production of peripheral blood mononuclear cells obtained from 45 IgA nephropathy patients was measured and then compared with that of healthy individuals. The level of IgA production was classified into an elevated group and a non-elevated group and comparisons were made with various clinical factors considered to be related to exacerbation of this disease. The results indicated that although there was no significant difference in immunoglobulin production of the peripheral mononuclear cells between IgA nephropathy cases and healthy individuals in the group not stimulated with pokeweed mitogen (PWM), the group stimulated with PWM revealed a production of IgA, IgG, and IgM which was significantly elevated (P less than 0.01). Also, within the group stimulated with PWM, hypertension, severe proteinuria and microscopic hematuria, elevated BUN and serum creatinine values, decreased 15-min PSP and creatinine clearance values, severe histological damage, and severe IgA deposition were observed more in the elevated IgA production group than in the non-elevated group. These findings suggest that an elevated IgA production plays an important role in the excerbation of this disease.

Adolescent↗
PubMed1989

[Immunochemical properties and immunohistological localization of human liver glutathione S-transferase isozymes].

The products of three human glutathione S-transferase (GST) loci (GST1, GST2 and GST3) were purified and their immunochemical properties as well as immunohistological localization in liver were studied. Three group of isozymes were different in molecular weight, substrate specificities and antigenicity. Two homodimers (type 1 and type 2) of GST1 which shows genetic polymorphism, were similar in immunochemical properties other than isoelectric point. Inactivity of GST1 0 was due to impaired protein synthesis. Immunohistologically, GST1 isozyme was homogeneously stained in cytoplasm of hepatocytes throught the lobule of liver showing GST1 1, GST1 2 and GST1 2-1 phenotypes. On the other hand, GST2 isozyme was stained in the cytoplasm as well as the nucleus of hepatocytes throughout the hepatic lobule in all cases. GST3 isozyme was strongly stained in biliary epithelium. These results indicate that the human liver GSTs are composed of three immunochemically distinct isozymes, which exhibit significant difference in inter-individual, specific cellular and organellar distribution.

Glutathione Transferase↗
PubMed1989

Serum soluble interleukin 2 receptor in patients with IgA nephropathy.

Serum soluble interleukin 2 receptor (IL-2 R) was determined by the ELISA method in 29 cases of IgA nephropathy and 50 healthy controls. The results showed that the value in IgA nephropathy cases was significantly higher than that in healthy controls. Furthermore, among the cases of IgA nephropathy, the value was significantly higher in the groups with hypertension, elevated serum IgA and depressed creatinine clearance than in that of the corresponding controls. These findings suggest that serum soluble IL-2 R can serve as a prognostic index of IgA nephropathy.

Adolescent↗
PubMed1989

[Lymphocyte function of pulmonary tuberculosis in the elderly].

The skin test to tuberculin purified protein derivatives (PPD) was examined in 161 cases of newly diagnosed active pulmonary tuberculosis. Tuberculin reaction was reduced in size with aging, and was significantly lower in the age group of 70 years or over than of less than 50. PPD- or PHA-induced proliferation tests of peripheral blood lymphocytes were examined in vitro, and suppression of lymphocyte proliferative reaction was shown especially on the number of activated T lymphocyte subsets (IL2-R or HLA-DR positive T lymphocytes) in the group of 70 years or over. These findings suggest that the suppression of cellular immunity caused in aged persons is one of the pathogenetic factors for pulmonary tuberculosis.

Aging↗
PubMed1989

[Clinico-immunological studies of pulmonary tuberculosis in the elderly].

We studied tuberculin reactivity and clinical course after starting chemotherapy in patients with active pulmonary tuberculosis divided by four age-groups less than 29, 30-49, 50-69 and 70 years and more. The skin test to tuberculin purified protein derivative (PPD) was examined in 178 cases of active pulmonary tuberculosis, 120 cases of lung cancer, 25 cases of atypical mycobacteriosis and 466 cases of the other respiratory diseases. The average size of tuberculin reaction in pulmonary tuberculosis decreased with age, but significantly higher than that in patients with other nontuberculous pulmonary diseases of the same age-group. The size of PPD skin test in the group of 70 years and more was significantly lower than other age-groups in pulmonary tuberculosis. We compared the time required for negative conversion of sputum by culture after primary chemotherapy among the different age-groups in pulmonary tuberculosis. It revealed that the time for negative conversion tended to be longer with age, and the time in the group 70 years and more was significantly longer than that of the group less than 29 years of age, although no significant differences in the radiographic severity and conditions of chemotherapy were observed. Finally, the PPD-induced lymphocyte proliferation test in vitro was done in newly diagnosed patients with pulmonary tuberculosis. The patients were divided into two groups by the size of PPD skin test (high responder more than 16 mm and low responder less than 15 mm of erythema induced by PPD).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Enterotoxin of Clostridium perfringens type A forms ion-permeable channels in a lipid bilayer membrane.

The enterotoxin of Clostridium perfringens type A was found to form ion-permeable channels in a lipid bilayer. A patch clamp technique was used to detect channel activities in an asolectin bilayer with incorporated enterotoxin. About 20% of the lipid bilayer patches examined showed rectangular or stepwise shift of membrane current. The shifts indicated the gating of ion-permeable channels in the patches. The channels showed high conductance (40-450 pS), no rectification in current-voltage curves and occasional long-lasting events. The significance of these findings is discussed in relation to the mechanism of action of the toxin.

Clostridium perfringens↗
PubMed1988

Proteases released in organ culture by acute dermal inflammatory lesions produced in vivo in rabbit skin by sulfur mustard: hydrolysis of synthetic peptide substrates for trypsin-like and chymotrypsin-like enzymes.

The purpose of these studies was to identify some of the extracellular proteolytic enzymes associated with the development and healing of acute inflammatory lesions. Lesions were produced in the skin of rabbits by the topical application of the military vesicant, sulfur mustard (SM). Full-thickness, 1-cm2 central biopsies of the lesions were organ-cultured for one to three days, and the culture fluids were assayed for proteases with a variety of substrates. When compared to culture fluids from normal skin, the culture fluids from both developing and healing SM lesions had three to six times the levels of proteases hydrolyzing two synthetic peptide substrates: (1) t-butyloxycarbonyl-Leu-Gly-Arg-4-trifluoromethylcoumarin-7-amide(Boc-Leu -Gly- Arg-AFC, herein abbreviated LGA-AFC), and (2) N-benzoyl-phenylalanine-beta-naphthyl ester (BPN). LGA-AFC is a substrate for trypsin, plasmin, plasminogen activator, thrombin, kallikrein, and the C3 and C5 convertases; BPN is a chymotrypsin and cathepsin G substrate. The culture fluids did not consistently hydrolyze four other synthetic peptide substrates or the proteins [14C]-casein and [14C]elastin. In order to determine the likely sources of LGA-AFCase and BPNase activity, we counted the number of granulocytes (PMNs), macrophages (MNs) and activated fibroblasts in histologic sections of developing and healing SM lesions, and we measured the levels of these enzymes in serum, in culture fluids of PMN and MN peritoneal exudate cells, and in culture fluids of two fibroblast cell lines. In SM lesions, serum and fibroblasts seemed to be the major source of LGA-AFCase, and serum alone the major source of BPNase. Tissue PMNs and MNs seemed to be only minor sources. The crusts of healing lesions, which were full of dead PMNs, seemed to be a rich source of both enzymes. In the SM lesion culture fluids, whether LGA-AFC and BPN were hydrolyzed by endopeptidases or only by exopeptidases could be determined by evaluating complex formation with alpha-macroglobulin proteinase inhibitors (alpha M). Endopeptidases, but not exopeptidases, are entrapped and inhibited by alpha M, because an internal peptide band in alpha M must first be hydrolyzed before molecular rearrangement (required for proteinase inhibition) occurs. The catalytic site of endopeptidases that are entrapped and inhibited by alpha M is known to remain active on (and reachable by) small synthetic peptide substrates such as LGA-AFC and BPN.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

Entry of human immunodeficiency virus (HIV) into MT-2, human T cell leukemia virus carrier cell line.

The ultrastructural features of early events in human immunodeficiency virus (HIV) infection of HTLV-I-carrying MT-2 lymphocytes were investigated by electron microscopy. Within 10 min after virus inoculation at 37 degrees C, the virus entered the cell in two ways; (1) the virus attached to the lymphocyte membrane and the viral core entered the cell after fusion of the viral envelope with the cell membrane, and (2) part of the cell membrane to which the virus was attached became invaginated, the virus became trapped in a phagosome and the viral core entered after the fusion of viral membrane with the vacuolar membrane. Thereafter, some cells were observed to form syncytia with multiple nuclei. When the proportion of anti-HIV antibody-reactive cells present exceeded 90%, virus production was strongly activated, and budding on the cell membrane was frequently observed.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Lysis of human immunodeficiency virus infected cells by TPA-type and non-TPA type tumor promoters.

We reported previously that TPA facilitates the replication of human immunodeficiency virus (HIV) and has a selective lethal effect on HIV-infected cells by a cytopathic effect induced by HIV. We have now studied the cytopathic effects of TPA-type tumor promoters (teleocidin, aplysiatoxin, and TPA) and the non-TPA type tumor promoters (palytoxin and thapsigargin) on MOLT-4/HIVHTLV-IIIB cells. All TPA-type and non-TPA type tumor promoters tested except palytoxin stimulated in HIV production three- to sevenfold, and caused more lysis of MOLT-4/HIVHTLV-IIIB cells than of the parental MOLT-4 cells. Fifty percent of the MOLT-4/HIVHTLV-IIIB cells were killed by teleocidin, aplysiatoxin, TPA and thapsigargin at concentrations of 2.0, 2.0, 1.0 and 10 ng/ml respectively, and by palytoxin at the very low concentration of 2.0 pg/ml. Moreover, combinations of one TPA-type tumor promoter and one non-TPA type tumor promoter--but not the combination of two TPA-type tumor promoters--had additive lethal effects, supporting the idea that TPA-type and non-TPA type tumor promoters exert their cytolytic effects by different mechanisms. These latter effects may be due to production of prostaglandin E2, which is commonly induced by both types of tumor promoters.

Carcinogens↗
PubMed1988

The effect of metoclopramide on the absorption and pharmacology of chlorpromazine in the rat.

The mechanism of interaction between metoclopramide (MCP) and chlorpromazine (CPZ) has been examined in rats. MCP given intraperitoneally 30 min before orally administered CPZ significantly enhanced the cataleptic and hypothermic effects of CPZ, and also initially increased its plasma and brain concentrations. However, MCP had no effect on the plasma and brain concentrations of CPZ given as an intravenous bolus, indicating that MCP interacts with CPZ during its intestinal absorption. Furthermore, co-administration of MCP (i.p.) with CPZ (p.o.) markedly accelerated gastric emptying compared with CPZ alone, and MCP (i.v.) did not alter the uptake of CPZ by the intestinal membrane. Therefore, it is concluded that MCP causes an increase in the rate of CPZ absorption, by accelerating the gastric emptying.

Animals↗
PubMed1988

Effect of immunoglobulin preparation on course of AIDS-related complex (ARC).

Relatively low dose treatment (150 mg/kg, once per two weeks) of a intravenous immunoglobulin (IVI) preparation has shown a beneficial effect on CD4/CD8 ratio and CD4 cell counts in two patients with AIDS-related complex (ARC). Since ARC generally progresses to AIDS with a marked reduction of CD4 cells or a marked inversion of CD4/CD8 ratio, this type of IVI treatment seems to be effective for obstructing or at least delaying the progression from ARC to AIDS.

AIDS-Related Complex↗
PubMed1988

Efficacy and tolerance of tiaprofenic acid during long term administration to rheumatoid arthritis patients.

In a multicentre trial, tiaprofenic acid was administered in a dosage of 600 mg/day for 12 months to 109 patients with rheumatoid arthritis. The results in 79 patients, who did not receive any other non-steroidal anti-inflammatory drugs concomitantly, were assessed. Of the 79 patients, 11 withdrew from the study within one year. The reasons for withdrawal were personal reasons in 4 cases, side effects or abnormal laboratory values in 2, no change or aggravation of symptoms in 2, improvement of symptoms in 2, and identification of systemic lupus erythematosus in one. Overall improvement was definite in 27 patients (34.2%) and slight in 21 patients (26.6%). Overall usefulness was definite in 30 patients (38%) and slight in 27 patients (34.2%). The duration of morning stiffness, joint index and Lansbury activity index showed significant improvement after 6 months' administration. Side effects were observed in 2 cases (2.5%) and abnormal laboratory results were seen in 3 (3.8%). These disappeared on either continuation or discontinuation of treatment.

Adult↗