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Biomedical subjects

Y Ohara

Publications and source records attributed to Y Ohara.

At least 127 records · Page 7Linked to original sources
PubMed1988

Problems in monitoring mutagenicity of human urine.

Blue-cotton (-rayon) adsorbable fractions of human urines were examined for mutagenicity in Salmonella typhimurium TA98 with metabolic activation. Ingestion of cooked beef caused significant increases in urinary mutagenicity that were comparable to that caused by cigarette smoking. When a sample obtained after ingestion of cooked beef was passed through a carboxymethyl cellulose column, the mutagenicity of the eluate was found to be almost one order of magnitude greater than that of the original sample, suggesting the presence of antimutagenic factors in the sample. The oleic acid content of the sample was not great enough to account for this phenomenon. Other urine samples subjected to column fractionation were found to contain the putative antimutagenic factors. This finding further confounds the monitoring of urinary mutagenicity.

Animals↗
PubMed1987

Mutagenic metabolites in urine and feces of rats fed with 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, a carcinogenic mutagen present in cooked meat.

To study the in vivo fate of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), a carcinogenic mutagen present in cooked meat, rats were fed MeIQx in the diet and their urine and feces were analyzed for the metabolites. The isolation procedure included specific adsorption of MeIQx derivatives to blue cotton and subsequent fractionations by thin layer chromatography on silica gel and by high pressure liquid chromatography. Attention was focused on mutagenically active metabolites. Three metabolites were isolated from the urine, and their structures were elucidated on the basis of 1H nuclear magnetic resonance, ultraviolet, and mass spectra. The first metabolite characterized was 2-amino-8-hydroxymethyl-3-methylimidazo[4,5-f]quinoxaline (Compound I), the second was 2-acetylamino-3,8-dimethylimidazo[4,5-f]quinoxaline (Compound II), and the third was 2-amino-8-methylimidazo[4,5-f]quinoxaline (Compound III). Compound I was isolated also from the feces. Compounds I-III were mutagenic to Salmonella typhimurium TA98 with metabolic activation. The mutagenic potency of Compounds I and II was as high as that of MeIQx, and that of Compound III was much lower than that of MeIQx.

Animals↗
PubMed1987

Inhibitory effect of myoglobin and hemoglobin on the direct-acting mutagenicity of protein pyrolysate heterocyclic amine derivatives.

We have shown in our earlier reports (Arimoto et al., 1980a, b) that hemin and some other porphyrins can inhibit the mutagenicity in Salmonella of heterocyclic amines derived from cooking of proteins. A direct interaction between hemin and the mutagens was implicated on the basis of the observation that some of the mutagens were inactivated when they had been metabolically converted into direct-acting mutagens before the treatment with hemin. Hemin is a bound constituent of various proteins including hemoglobin and myoglobin, which are abundantly present in the blood and muscles, respectively. An interesting question is whether or not hemoglobin and myoglobin can inhibit the activities of the mutagenic heterocyclic amines.

Amines↗
PubMed1987

Comparative studies on clinical features and CSF proteins of motor neuron disease patients.

Clinical features such as types of diseases, sex ratio, age of onset, sites of initial involvement, the appearance of bulbar signs, and duration of illness were studied in 52 patients with motor neuron disease (MND) with a special reference to immunoglobulin in cerebrospinal fluid (CSF) and serum. Although MND has been thought to be a degenerative disease of unknown cause, our data suggested there are some immunological abnormalities in this disease. The duration of illness and the abnormalities of CSF immunoglobulins appeared to be correlated with the type of disease and the site of initial involvement. However, whether or not these abnormalities in CSF immunoglobulins are directly related to the pathogenesis of MND remains unclear.

Adult↗
PubMed1987

Endocrinological abnormalities in myotonic dystrophy: consecutive studies of eight tolerance tests in 26 patients.

We studied endocrine functions of the hypothalamus, pituitary, thyroid, gonad, adrenal and pancreas in 26 patients with myotonic dystrophy. The following findings were obtained: (1) Hyporesponsivenesses of HGH to insulin, arginine and L-dopa test were observed in 25%, 45% and 54.5% of patients, respectively. To the administration of sulpiride and TRH, hypo- or hyperresponses of plasma PRL were observed in 4 or 2 patients, respectively. (2) Depressed plasma levels of testosterone were observed in 4 patients and those of estradiol were observed in 3 patients. Among these 7 patients, five were hypergonadotropic and the remaining two were hypogonadotropic. From the data of plasma cortisol and urinary 17-OHCS, the adrenal functions in patients with myotonic dystrophy were considered to be normal. The renin-angiotensin-aldosterone systems in these patients were considered to be grossly normal. (3) Basal levels of T3, T4 and free T4 were within the normal ranges, but 6 of 19 patients showed low levels of 131I-uptake and 11 of 24 patients showed reduced BMR values. (4) The basal level of plasma insulin was elevated in 5 patients. Insulin responses to oral glucose were exaggerated and delayed in 21 of 26 patients. From these results and the statistical evaluation of each laboratory and clinical data, we concluded that 1) the degrees of disturbances of endocrine functions are at random in each patient. 2) The measures of intellectual function obtained by WAIS were directly correlated with basal levels of TSH, but inversely with basal levels of somatostatin. No specific correlation was found between endocrinological disturbances and neurological severities. 3) Impairment of some endocrine functions, such as the gonadal, thyroid and somatotroph functions, was closely correlated with age and the duration of disease.

Adolescent↗
PubMed1987

Cell-mediated cytotoxicity-supporting activity of various human gammaglobulin preparations.

Antibody activity, especially that involved in the reaction of antibody-dependent cell-mediated cytotoxicity (ADCC), of five commercially available human gammaglobulin preparations (standard, pepsin-treated, plasmin-treated, polyethylene glycol-fractionated and S-sulfonated gammaglobulin) was measured. All these gammaglobulin preparations had high titers of hemagglutination inhibition and neutralizing antibody against measles virus. In ADCC reaction, the pepsin-treated gammaglobulin preparation showed no antibody activity. The standard gammaglobulin preparation showed weak activity only when highly diluted. The remaining three preparations showed high activity. Though the S-sulfonated gammaglobulin preparation showed no activity in ADCC reaction, it showed high activity after reconversion by means of oxidation and reduction in vitro. The plasmin-treated gammaglobulin preparation showed greater activity than the polyethylene glycol-fractionated preparation of the optimal concentration. In ADCC tests using the plasmin-treated gammaglobulin preparation, K cell activity was strongly inhibited by Hg (thimerosal), while, in those using the standard gammaglobulin preparation, the activity was hardly influenced by Hg, suggesting that the low ADCC activity of the standard gammaglobulin preparation of high concentrations was due to the inhibitory effect of aggregated immunoglobulin G molecules.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1987

[Cefuzonam, a new cephem antibiotic in the field of pediatrics. Concentrations in serum and clinical efficacy].

A new cephem antibiotic, cefuzonam (L-105, CZON) was studied for its concentrations in serum and clinical efficacy in the field of pediatrics. To examine the concentration of CZON in serum, 20 mg/kg of CZON was administered by intravenous drip infusion to a male patient of 6 years and 7 months. The half-life of the drug in serum was 0.97 hour after administration. CZON was administered to 7 cases of pediatric infections, and clinical result were "excellent" in 4, "good" in 1, "poor" in 2: the efficacy rate was 71.4% or 5 cases out of 7. As an adverse reaction, eruption was observed in 1 patient.

Bacterial Infections↗
PubMed1986

Hyperreactivity of lymphocytes to streptolysin O and lack of plasma inhibitory factor (s) in patients with mucocutaneous lymphnode syndrome.

Lymphocyte activation by streptolysin O (SLO) and factors in the plasma which inhibit the response to SLO were examined in 19 patients with mucocutaneous lymphnode syndrome (MCLS), 54 age-matched (6 months-6 years) normal children, 41 normal children older than 6 years and 10 normal adults. In normal children younger than 6 years, the response to SLO was weak and in many cases no response was seen. On the other hand, in the patients with MCLS, the response of lymphocytes to SLO was high and comparable to the response in adults and children older than 6 years. The DNA synthesis of lymphocytes stimulated by SLO was inhibited almost completely by autologous or allogeneic plasma of many of the normal children and adults. The plasma of patients with MCLS did not inhibit, but rather enhanced the response to SLO. These results suggest that the increased response of lymphocytes to SLO and the lack of plasma inhibitory factors in patients with MCLS may be due to the immune response to the pathogen of MCLS, as yet undiscovered.

Adult↗
PubMed1986

Evaluation of the mutagenicity of 1,N6-ethenoadenine- and 3,N4-ethenocytosine-nucleosides in Salmonella typhimurium.

To provide supporting evidence for the hypothetical involvement of etheno-derivative formation in DNA in chloroacetaldehyde-mediated mutagenesis, etheno nucleosides were examined for their direct-acting mutagenicity in Salmonella typhimurium strain TA100. The results, however, have shown that 1,N6-ethenoadenosine, 1,N6-ethenodeoxyadenosine, 3,N4-ethenocytidine and 3,N4-ethenodeoxycytidine lack mutagenicity in this test system. A lesson learned in this study is that 3,N4-ethenocytosine nucleosides prepared synthetically or obtained from commercial sources can give false positive mutagenicity due to mutagenic contaminants.

Adenine↗
PubMed1986

Synthesis of a mutagenic nucleoside, 2'-deoxy-2-(p-nitrophenyl)-adenosine.

The reaction of 2-amino-6-chloropurine riboside with i-amyl nitrite in benzene in the presence of Cu2O, followed by treatment with NH3/MeOH gave 2-phenyladenosine (1). The crude sample of 1 was found to be mutagenic to bacteria (Salmonella typhimurium TA 98 and TA 100, without metabolic activation). When this material was subjected to high pressure liquid chromatography, the mutagenic activity was found only in contaminating minor components, whose structures were assigned as 2-(m- and p-nitrophenyl)-adenosines (2m,p). In order to study structure-activity relationships, several nucleoside and base analogues were synthesized. Among them, 2'-deoxy-2-(p-nitrophenyl)-adenosine (8) was the most potent mutagen as tested either with TA 98 or TA 100.

Adenosine↗
PubMed1985

Activation and inhibition of transcription by supercoiling.

Stimulation of transcriptional activity in vitro is observed at low and moderate negative superhelical densities up to the level of the natural superhelical form of the plasmid pBR322. We have isolated and identified three specific transcription products: ampicillinR RNA, tetracyclineR RNA and "Rep" RNA. Their enhancement of transcription occurs at different levels of superhelicity, suggesting a sequence-dependent structural alteration of promoters upon changes of axial writhe, which may generate kink formation. The activation of transcription is drastically inhibited at higher specific linking differences exceeding that of the natural superhelical form of pBR322, which is correlated with a transition from the right-handed B to a left-handed DNA form of particular sequences induced by supercoiling. We have identified a new stop point in the beta-lactamase coding sequence composed of eight alternating purine-pyrimidine residues which, at higher torsional stress, causes transcription to stop, leading to the synthesis of a short RNA of about 55 nucleotides instead of AmpR RNA (about 580 nucleotides). In the "Rep" promoter, two alternating purine-pyrimidine segments are found, which conformational change at higher superhelical densities may be implicated in repression of "Rep" RNA synthesis. The enhancement and inhibition of transcription by supercoiling support the role of energetic and structural changes in topologically constrained DNA as elements of a control mechanism.

Autoradiography↗
PubMed1985

Detection of antibody to M protein of measles virus in patients with subacute sclerosing panencephalitis: a comparative study on immunoprecipitation.

Consistent results have not been obtained yet on the presence of antibody to the M protein of measles virus in the sera of patients with subacute sclerosing panencephalitis (SSPE). We performed a comparative study on various immunoprecipitation systems which appeared in the literature and found that the difference in the composition of the solubilizing buffer produced a large variety of results on the immunoprecipitation. [35S]Methionine-labeled Vero cells infected with the Edmonston strain of measles virus were solubilized by 10 different buffers and reacted with hyperimmune rabbit serum to whole virus, monospecific antisera to H, NP, and M proteins of the virus, normal adults' sera, and the sera from 16 SSPE patients. The immune complex was absorbed by protein A and both solubilization and precipitation rates were compared with each viral protein. Although viral proteins were solubilized by all buffers, the solubilization rate varied considerably. M protein was solubilized and was not coprecipitated nonspecifically with any of the other viral proteins. Purified protein A conjugated to Sepharose was preferable to Staphylococcus aureus for absorption of the immune complex since the latter absorbed both viral and host proteins nonspecifically. The precipitation rates of the viral proteins also varied according to the buffers. Better solubilization of the viral proteins seemed to reduce their rate of precipitation for which the presence of SDS may be responsible, and the presence of the protease inhibitors may also affect the results of immunoprecipitation. Detection of M protein in the immunoprecipitates was largely influenced by the kind of buffer used: some buffers could detect it clearly, but others could not defect it at all. Among the solubilizing buffers tested, Saleh's buffer (Virology 93: 369-376 (1979)),, which contains 0.5% DOC and 0.5% Triton X-100, was most reliable for detection of the anti-M antibody in the rabbit serum, because it showed a high solubilization and high precipitation rates of viral proteins without nonspecific absorption by protein A or coprecipitation of M proteins with any of the other proteins. Using this buffer, we could definitely detect M proteins in the immunoprecipitates from the sera of all six healthy adults and 15 out of 16 patients with SSPE. It was found, however, that the amount of M proteins in SSPE patients was lower than that in healthy adults and varied considerably.

Adult↗
PubMed1985

Mutagenicity of human urine caused by ingestion of fried ground beef.

On ingestion of fried ground beef by humans, the urinary mutagenicity, as examined by the Ames test, increased rapidly and then decreased during a period of 12 hr to resume the original low level. The excreted mutagens were shown to differ from 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, the major mutagen in the cooked beef.

Animals↗
PubMed1985

[The therapeutic effects of aspoxicillin on various infectious diseases in children].

Clinical application to ascertain the effects of aspoxicillin (ASPC), a new semisynthetic penicillin antibiotic, upon several infectious diseases of children was performed in 7 cases with pneumonia, 5 cases with acute bronchitis, each case with tonsillitis, enterocolitis, urinary tract infection and suspected sepsis. ASPC was injected by drip infusion and the dosage was 63-117 mg/kg/day in 3 and 4 times a day. Clinical efficacy obtained as "excellent" was in 7 cases, "good" in 8 cases "poor" in 1 case, and efficacy rate was 93.8%. From the bacteriological point of view, eliminated in each of H. influenzae, H. parainfluenzae, group A beta-Streptococcus and unchanged in a case of E. coli. There were transient thrombocytopenia in 2 cases and eosinophilia in 3 cases.

Adolescent↗