Abnormal threshold properties of fluxon propagation in a resistively coupled Josephson transmission line.
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Biomedical subjects
Publications and source records attributed to A Matsuda.
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Pancreatic beta-cell secretion after oral glucose or intravenous glucagon stimulation was studied in newly diagnosed patients with non-insulin-dependent diabetes mellitus (NIDDM) before and after glycemic control by diet treatment alone. Insulin secretion to oral glucose showed significant improvement, while C-peptide release by glucagon showed no significant difference before and after diet treatment. The finding suggests that pancreatic beta-cell response to oral glucose varies with different metabolic states, but this is not so after glucagon stimulation in NIDDM patients.
The effect of 3'-azido-2',3'-dideoxythymidine (AZT) on the human immunodeficiency virus (HIV)-associated giant cell formation was studied in vitro. For this purpose we developed a coculture system using Molt-4 and its virus-producing cell, Molt-4/HTLV-III, which induced syncytia very efficiently. Treatment of the cocultures with 1 and 5 microM of AZT did not inhibit induction of multinucleated giant cells, although only 0.1 microM AZT resulted in almost complete inhibition of HIV replication in Molt-4 cells by cell-free virus infection. This was also evidenced by the assays for viral antigen-positive cells, reverse transcriptase activity, and virus particles released from cell cultures after AZT treatment. When the cocultures were treated with 1% neutralizing antibody (NA) from HIV-infected individuals alone, giant cell formation was inhibited to some extent. However, the concomitant treatment of culture with AZT and NA resulted in much stronger inhibition of giant cell formation. The amount of CD4 antigens on the surface of cells was reduced greatly in the HIV producer cells (Molt-4, H9, and MT-4 cells) as compared to their HIV-free counterparts. These data suggest that (1) both CD4 antigen and viral antigens on the surface of cells play central roles in the induction of multinucleated giant cells and (2) AZT is more effective in inhibition of viral spread in patients with higher NA, probably at an earlier stage of the disease than in patients with lower NA titer.
The nucleotide (nt) sequences of inverted terminal repeats (ITR) from human adenovirus (Ad) 19, bovine Ad1 (BAd1), bovine Ad3 (BAd3), canine Ad2 (CAd2) and an avian Ad, EDS-76, were determined. The length of the ITR sequence was 160 bp in Ad19, 159 bp in BAd1, 195 bp in BAd3, 196 bp in CAd2 and 52 bp in EDS-76. CAd2 had the longest ITR among the examined Ads, BAd3 the second longest, and EDS-76 had the shortest ITR. A TAAT sequence located between the 10th and 13th nt counted from the ends was conserved in all Ads examined so far. To determine phylogenetic relationships among human and animal Ads, sequences of their ITRs were compared, and a phylogenetic tree was constructed by using the maximum-likelihood method. It is the method involving statistical analysis of computing the probability of a particular set of sequences on a given tree and maximizing this probability over all evolutionary trees [Felsenstein, J. Mol. Evol. 17 (1981) 368-376]. From these analyses, it was found that members belonging to the same human Ad subgenus are related closely to each other, whereas representatives of different human subgenera are distributed rather divergently among animal Ads.
It is generally accepted that human immunodeficiency virus (HIV) is the etiologic agent of the acquired immunodeficiency syndrome and related diseases. In this report, we demonstrate the antiviral effect of nucleoside analogs 2',3'-didehydro-2',3'-dideoxythymidine (DHT) and 2',3'-didehydro-2',3'-dideoxycytidine (DHC) by using human T-cell lymphotropic virus type I-carrying MT-4 cells, which are extremely susceptible to HIV infection. These agents efficiently inhibited the cytopathic effects and expression of HIV-specific antigens in MT-4 cells after infection of the virus. Both DHT and DHC also strongly blocked viral replication as determined by our quantitative bioassay system using a plaque-forming assay. These antiviral effects were obtained at concentrations at which the drugs produced little or no toxicity and were comparable to those with 3'-azido-3'-deoxythymidine and 2',3'-dideoxynucleosides. These findings warrant further investigation of the use of DHT and DHC for the treatment of the acquired immunodeficiency syndrome and related diseases.
Pseudomonas sp. strain SE83 converts cephalosporin C and 7 beta-(4-carboxybutanamido)cephalosporanic acid (GL-7ACA) to 7-aminocephalosporanic acid (7ACA). A DNA library of this strain was constructed in Escherichia coli and screened for the ability to deacylate GL-7ACA to 7ACA. Apparently, two distinct genes, designated acyI and acyII, were cloned on 4.8- and 6.0-kilobase-pair BglII fragments, respectively. The enzymes encoded by the two genes showed different substrate specificities, and the acyII-encoded enzyme was found to yield 7ACA from cephalosporin C by direct deacylation. Expression of the two genes in E. coli was strongly dependent on a promoter of the vector. The coding regions for acyI and acyII were localized on the 2.5- and 2.8-kilobase-pair fragments, respectively, by subcloning experiments, and high expression of both genes was obtained by placing them under the control of the lacUV5 promoter. The acyII-encoded enzyme was purified and shown to be composed of two nonidentical subunits with molecular weights of 26,000 and 57,000. Maxicell analysis revealed three acyII-specific polypeptides, two of which corresponded to the above subunits. The third polypeptide with a molecular weight of 83,000 was suggested to be the precursor of both subunits.
Two genes, acyI and acyII, for distinct cephalosporin acylases from Pseudomonas sp. strain SE83 (A. Matsuda, K. Matsuyama, K. Yamamoto, S. Ichikawa, and K.I. Komatsu, J. Bacteriol. 169:5815-5820, 1987) were sequenced. Each sequence contained a single open reading frame for two nonidentical subunits, predicting a common precursor. Some homologies at the amino acid level were found between the acyII-encoded enzyme, but not the acyI-encoded one, and other related acylases.
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Serum C-peptide responses to glucagon and daily urine C-peptide excretion in successive periods of different treatment in two groups of patients with non-insulin-dependent diabetes mellitus (NIDDM) (mean interval between two tests less than 1 month) were compared. In group A patients (n = 8), the glycemic control was improved after transferring the treatment from sulfonylurea (SU) to insulin (fasting plasma glucose: SU: 192 +/- 47, insulin: 127 +/- 21 mg/dl, mean +/- S.D., p less than 0.01). Fasting serum C-peptide immunoreactivity (CPR) was significantly lower at the period of insulin treatment (SU: 1.93 +/- 1.01, insulin: 1.47 +/- 0.79 ng/ml, p less than 0.05), but there was no difference in the increase in serum CPR (maximal--fasting) (delta serum CPR) during glucagon stimulation in the two periods of treatment (SU: 1.70 +/- 0.72, insulin: 1.47 +/- 0.98 ng/ml). In group B patients (n = 7), there was no significant difference in glycemic control after transferring the treatment from insulin to SU (fasting plasma glucose: insulin: 127 +/- 24, SU: 103 +/- 13 mg/dl). Fasting serum CPR was significantly lower during the period of insulin treatment (insulin: 1.39 +/- 0.64, SU: 2.21 +/- 0.86 ng/ml, p less than 0.025), but delta serum CPR during glucagon stimulation still showed no significant difference between the two periods (insulin: 1.97 +/- 1.16, SU: 2.33 +/- 1.57 ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS)
In an attempt to determine the level and heat stability of residual catalase in somatic cells of acatalasemic Japanese, skin fibroblasts from an acatalasemic subject were cultured, and the catalase activity of the cultured fibroblasts was compared with that of cultured normal fibroblasts. Catalase activity was determined using an oxygen electrode. The residual catalase activity in cultured acatalasemic fibroblasts was 10% of the normal. The heat stability at 55 degrees C of residual catalase in the acatalasemic fibroblasts was similar to that of normal fibroblasts.
We recently reported a new case of abnormal insulinemia with LeuA3 insulin. Herein, we measured urinary insulin clearance during oral glucose tolerance tests in proband with abnormal insulinemia (44-yr-old female), three affected family members, two unaffected family members, two other hyperinsulinemic patients with obesity, five non-insulin-dependent diabetic patients, and five normal control subjects. Urinary insulin-to-creatinine clearance ratio in the proband and her affected family members was 0.22 X 10(-3) +/- 0.07 (mean +/- SD, n = 4) and was markedly reduced compared with those of other groups: 1.73 X 10(-3) in two unaffected family members, 2.77 X 10(-3) in two other hyperinsulinemic patients with obesity, 2.99 X 10(-3) +/- 1.48 in five non-insulin-dependent diabetic patients, and 2.54 X 10(-3) +/- 0.67 in five normal control subjects. In contrast, urinary C-peptide clearance in these groups was not significantly different from controls. Binding of immunopurified insulins extracted from urine of the patients with abnormal insulinemia to guinea pig kidney membrane was slightly decreased (71% of standard insulin), in contrast with the observation that serum insulin of the proband had much less receptor-binding activity. Reverse-phase HPLC analysis of the immunopurified insulin of the proband revealed that the ratios of normal insulin to abnormal insulin were 8:3 in urine and 1:7 in serum, respectively. These results suggest that excretion of abnormal insulin in urine is much less than that of normal insulin.
Antitumor activity of peplomycin (PEP) against 7,12-dimethylbenz(a)anthracene (DMBA)-induced rat mammary tumors was compared with activities of bleomycin (BLM) and doxorubicin (adriamycin, ADM). Drugs were administered subcutaneously 3 times weekly (24 times in total) starting on 75 days after an intravenous administration of DMBA. PEP strongly inhibited the growth of mammary tumors detected at the start of the treatment, and some of the tumors disappeared and regressed upon the administration of PEP. The number of stable tumors was larger and the number of progressed tumors smaller in the PEP-treated group than in the control group. Moreover, PEP exhibited strong growth inhibitory effect with slight delay of tumor appearance against mammary tumors appeared during the treatment period. These antitumor effects of PEP were greater than those of BLM, a parent compound of PEP, and almost comparable to those of ADM.
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Concentration of metallic mercury in the arterial blood was higher in acatalasemic mice after exposure to 3.45 mg/m3 for 10 minutes in comparison with normal mice, whereas concentration of mercuric ion was lower in acatalasemic mice than in normal mice. Thus, the ratio of metallic mercury to total mercury in the arterial blood of acatalasemic mice was 5.86 +/- 3.61%, which was statistically significantly higher than the value (1.36 +/- 0.65%) of corresponding normal mice. The mercury concentration and distribution in the brain and liver of acatalasemic mice were higher than those in normal mice. Data indicate that the concentration of metallic mercury in the arterial blood of acatalasemic mice was higher than that of normal mice and that metallic mercury soluble in lipids is likely transferred to the brain and liver from the blood. Conclusively, metallic mercury in the arterial blood is the biologically active form for transferring mercury from blood to organs.
Cord blood mononuclear cells (MNC) were defective in their ability to produce interferon-gamma (IFN-gamma) on stimulation with phytohemagglutinin (PHA) or recombinant interleukin 2, whereas cord MNC could induce comparable amounts of IFN-gamma with adult controls on stimulation with a streptococcal preparation, OK-432. Moreover, irradiation of cord MNC with 1,500 rad before PHA stimulation could restore the IFN-gamma production. Kinetic studies indicated that such augmentation of IFN-gamma production by irradiation was evident when cord MNC were irradiated before or by 12 hr of PHA-stimulated culture. But irradiation after 18 hr or more of PHA stimulation did not exert any significant augmentation on IFN-gamma production by cord MNC. It seemed most likely that the ability of IFN-gamma production is already mature at birth, but radiosensitive suppressor effectors on IFN-gamma production are activated within cord MNC at an early stage of PHA stimulation, resulting in poor IFN-gamma production by cord MNC. PHA-induced IFN-gamma production by OKT3+, OKT4+, and OKT8- cord cells were markedly enhanced by irradiation with 1,500 rad before the culture. Coculture experiments disclosed that cord OKT4+ cells, but not OKT4- cells, when prestimulated with PHA for 24 hr, exerted active suppression on PHA-induced IFN-gamma production by adult MNC in a dose-dependent manner. These results suggested that radiosensitive suppressor effectors on IFN-gamma production were induced within the OKT4+ T cell subset of cord MNC on PHA stimulation.
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In the present study, we assigned a geographical range to promote community health service planning according to the life-behavior spaces of inhabitants in Fukuoka prefecture and regarded the country-life zone, defined by the Ministry of Construction, as a region in which health services should be investigated. The social and economic characteristics of each individual region were then analyzed. As a result, four factors related to "Industrialization" and "Urbanization" were detected. Further, the states of space distribution of medical care facilities and medical care-related facilities were clarified, and relationships between the states and the above socio-economic characteristics were investigated. The states of space distribution in both facilities in Fukuoka prefecture were proved to be remarkably similar on an axis of the "Accumulation of Urbanism" factor. Moreover, Path Analysis was performed in order to clarify the patterns of treatment received by the inhabitants, and a model of these trends in relation to health care received was constructed, highlighting problems in the necessary planning of health service provision. It was specifically indicated that the problem of aging in Chikuho region would be an important factor affecting such planning in the future. We also analyzed the present state of emergency medical services in Fukuoka prefecture and the activities of health nurses in each individual region.
Carbocyclic inosine is a potent inhibitor for the growth of the promastigote form of Leishmania tropica and Leishmania donovani. In culture, the EC50 values of carbocyclic inosine are 8.3 X 10(-8) and 1.3 X 10(-7) M for the promastigotes of L. tropica and L. donovani, respectively. On the other hand, it is less toxic towards mouse mammary tumor FM3A cells: the EC50 value is 2.7 X 10(-4) M. Carbocyclic inosine is metabolized by Leishmania promastigotes to give carbocyclic adenosine-5'-triphosphate (aristeromycin-5'-triphosphate) and carbocyclic guanosine-5'-triphosphate. This metabolic conversion provides a mechanism for the parasite-selective toxicity of carbocyclic inosine.