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Biomedical subjects

H Sakurai

Publications and source records attributed to H Sakurai.

At least 415 records · Page 23Linked to original sources

Methylated cytosine level in human liver DNA does not decline in aging process.

In order to ascertain a generality of the age-dependent decrease in DNA methylation level among different mammalian species, methylated cytosine contents in human liver and spleen DNA at different ages have been determined using high performance liquid chromatography (HPLC). Unexpectedly, the liver DNA revealed no appreciable decline with age while the spleen DNA showed a slight reduction. It indicates that a decrease of methylation level in genomic DNA is not a common denominator of age-related changes in mammals.

Adolescent↗

Gastric emptying after pancreatoduodenectomy with total stomach preservation and selective proximal vagotomy.

This study evaluates postoperative gastric emptying following a new method of pancreatoduodenectomy with total stomach preservation and selective proximal vagotomy performed on 10 patients with diseases affecting the head of the pancreas, 7 being malignant and 3 benign. Reconstruction was carried out using the Billroth I and Billroth II techniques in 5 patients each, respectively. Early postoperative gastric emptying was evaluated by the time before intragastric tube removal and the resumption of oral intake, as well as by barium gastric radiography, while late postoperative gastric emptying was evaluated by the acetaminophen method. No difference was seen in early postoperative gastric emptying between the two surgical techniques, the mean time which elapsed before intragastric tube removal being 4.4 days for the Billroth I and 4.5 days for the Billroth II patients, and the mean time until the resumption of oral intake being 6.8 days for the Billroth I and 7.0 days for the Billroth II patients. A significant delay in gastric emptying was seen in the Billroth II patients compared to a normal control group, 30 and 45 min after acetaminophen administration, but the difference in gastric emptying between the Billroth I and II patients was not significant. Moreover, both techniques impaired gastric emptying much less than Traverso's pylorus-preserving pancreatoduodenectomy.

Aged↗

Four-year follow-up of effects of toluene diisocyanate exposure on the respiratory system in polyurethane foam manufacturing workers. I. Study design and results of the first cross-sectional observation.

A 4-year cohort study was designed to assess the exposure-effect relationship of working in polyurethane foam (PF) manufacturing factories with exposure to toluene diisocyanate (TDI) and its effects on the respiratory system. This paper describes the results of the first cross-sectional observations. The study population included 90 male workers who had been working in PF factories for 0.5-25 years (mean 13.3 years) (PF workers) and 44 reference workers in the same factories. The mean exposure concentration of TDI calculated from 129 personal samples was 3.2 ppb. Peak exposure excursions above 20 ppb occurred in 16 of 129 samples. Pulmonary function and its change during the working day as assessed by examining the forced expiratory flow-volume curve, respiratory impedance, and airway resistance and specific airway conductance were not different in the PF workers from those in the reference workers. Chest X-radiographs did not show any noteworthy radiological changes. Prevalences of "phlegm in winter," "nasal stuffiness or discharge in winter," and "irritation of eye and throat mucous membranes" were significantly higher in the PF workers. The findings indicate that TDI exposure at levels around 3 ppb may not adversely affect the pulmonary function over many years of exposure of those who are not hypersensitive to TDI. The causal chemicals inducing some respiratory and irritative symptoms could not be specifically identified since the PF workers were exposed not only to TDI but also to other irritative agents in the PF manufacturing processes.

Adolescent↗

Four-year follow-up of effects of toluene diisocyanate exposure on the respiratory system in polyurethane foam manufacturing workers. II. Four-year changes in the effects on the respiratory system.

Fifty-seven polyurethane foam manufacturing workers (PF workers) and 24 reference workers were followed for 4 years to clarify the effects on pulmonary function of working in PF factories with exposure to toluene diisocyanate (TDI). No significant differences in the average annual losses (AALs) of pulmonary function for 4 years were observed among the 28PF workers whose TDI exposure levels were very low (mean = 0.1 ppb, group L), the remaining 29 PF workers with mean TDI exposure of 5.7 ppb (group H), and the reference workers. However, 15 PF workers in group H who had experienced peak exposure excursions to 30 ppb or above with a mean concentration of 8.2 ppb showed significantly larger AALs in percentage maximal mid-expiratory flow, forced expiratory volume in 1 s ratio to vital capacity (FVC), and forced expiratory flow at 25% of FVC than expected, and significantly larger AALs in some obstructive pulmonary function indices than those of the 14 remaining PF workers in group H whose peak exposure excursion levels were 3-14 ppb with a mean time-weighted average (TWA) of 1.7 ppb, group L, and the reference workers. These findings suggest that the peak exposure excursion level of TDI might be important in inducing obstructive pulmonary function changes in the PF workers rather than the TWA exposure levels, though further comparative studies of the AAL in those who are exposed to different peak exposure excursion levels but the same mean exposure levels are necessary. From the standpoint of prevention, the proposition that peak exposure excursion levels exceeding 20 ppb should be avoided is reasonable.

Adult↗

Acute and subacute inhalation toxicity of silane 1000 ppm in mice.

Male ICR mice were exposed to silane 1000 ppm, a concentration 200 or 2000 times higher than the recommended occupational exposure limits by many countries and academic associations, for 1, 2, 4, and 8 h (phase I study) and for 6 h/day, 5 days/week, over 2 and 4 weeks (phase II study). Hematological and biochemical studies were performed, and the animals were examined for histopathological lesions of the cornea, nasal cavity, respiratory tract, lung, liver, kidney, spleen, pancreas, thymus, thyroid, bone marrow, salivary glands, esophagus, and testis. All mice in both studies survived until they were sacrificed. In the phase I study, no exposure-related changes were found as a result of the hematological, biochemical, or histopathological examinations. In the phase II study, hematological and biochemical examinations failed to reveal any exposure-related changes, but mild irritation, manifested in the form of a small amount of exudate (eight out of ten animals), and inflammatory cells and/or necrotic cells on the nasal mucosa (six out of ten animals) was observed in the mice exposed to silane for 4 weeks. These findings suggest that silane toxicity and irritation are not severe.

Administration, Oral↗

Molecular analysis of a HTLV-IpX defective human adult T-cell leukemia.

Fresh and cultured leukemia cells from an adult T-cell leukemia (ATL) patient which possessed gag and env gene defective human T-cell leukemia virus type I (HTLV-I) provirus genome were molecularly analyzed. Cells from both fresh and the established cell line, named KB-1 showed identical surface markers of helper T cells, expressed the interleukin 2 (IL-2) receptor and had an identical defective HTLV-I provirus genome with deletions of the gag and env genes involving pX gene exon 2. The KB-1 cells grew vigorously in vitro, even in the absence of IL-2 and the culture supernatant of KB-1 contained a large amount of IL-2. Neither pX mRNA nor p40(TAX) protein was detected in the KB-1 cells. The collective evidence suggests that the pX gene was not functioning in this particular ATL case. The biological function of the HTLV-I genes, especially the pX gene is discussed in relation to the early and late leukemogenesis of ATL.

Blotting, Southern↗

Pattern of gonadotropin-releasing hormone (GnRH)-like stimuli sufficient to induce follicular growth and ovulation in ewes passively immunized against GnRH.

The pattern of GnRH-like stimuli capable of inducing follicular growth, ovulation, and luteal function was evaluated in ewes passively immunized against GnRH. The estrous cycles of 30 regularly cyclic sheep were synchronized using vaginal pessaries impregnated with a synthetic progestogen. Animals were passively immunized against GnRH (groups 2-5, n = 6) or the carrier protein, keyhole limpet hemocyanin (KLH; group 1, n = 6), at the time of pessary removal (PR). Circhoral delivery of saline (groups 1, 2, and 5) or low amplitude GnRH agonist (des-Gly10 GnRH ethylamide [100 ng/hourly pulse]; groups 3 and 4) was initiated at PR and continued for 3 (groups 4 and 5) or 12 days (groups 1-3). In groups 4 and 5, the amplitude of the GnRH-like stimulus was increased to 800 ng/hourly pulse (stimulus-shift) during the 24-h period beginning 72 h after PR. The amplitude of the hourly stimulus was adjusted to 100 ng/pulse 96 h after PR and continued at that level to Day 12. The endocrine changes associated with follicle growth and maturation (serum concentrations of estradiol [E2] above 10 pg/ml), ovulation (surge-like secretion of LH and FSH), and normal luteal function (serum concentrations of progesterone [P] above 2 ng/ml) were evident in ewes passively immunized against KLH (group 1). In this group, the preovulatory surge of gonadotropins was noted 48.7 +/- 1.2 h after PR. These endocrine events were blocked by passive immunization against GnRH (group 2).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Stimulation of cultured cerebellar granule cells via glutamate receptors induces TRE- and CRE-binding activities mediated by common DNA-binding complexes.

By use of nuclear mini-extracts prepared from cultured cerebellar granule cells in a gel-mobility assay, exogenous N-methyl-D-aspartate (NMDA) or kainate was shown to increase both 12-O-tetradecanoylphorbol 13-acetate-responsive element (TRE)- and cyclic AMP-responsive element (CRE)-binding activity. These increases were specifically prevented by the NMDA receptor antagonist D,L-2-amino-5-phosphonovalerate and the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione, respectively. The increase of TRE-binding activity was dependent on de novo protein synthesis, and its inductions by both NMDA and kainate required extracellular Ca2+. TRE-binding activity was competitively inhibited by the CRE, and vice versa, showing higher DNA-binding affinity to the CRE than to the TRE. A proteolytic clipping bandshift assay demonstrated that the increase in CRE-binding activity could be mediated by the TRE-binding activity. Thus, the TRE-binding activity cross-binding to the CRE could be activated by NMDA or kainate stimulation. The involvement of c-Fos or Fos-related proteins in the TRE- and CRE-binding complexes was shown by a supershift gel-mobility assay using anti-c-Fos antiserum.

2-Amino-5-phosphonovalerate↗

Biological monitoring of workers exposed to acetone in acetate fibre plants.

Concentrations of acetone in urine, alveolar air, and blood were measured by gas chromatography with flame ionisation detection for 110 subjects occupationally exposed to acetone (mean 372 ppm) in three factories. Significant relations were found between the time weighted average environmental concentration and the concentration in the biological samples. The strongest correlation was between the concentration of acetone in urine and the degree of exposure (r = 0.71, 95% CI 0.64-0.77). This suggests that urinary acetone concentration is the best biological index of occupational exposure to acetone.

Acetone↗

[Effects of ascorbic acid on the metabolic fate and the free radical formation of iproniazid].

The effects of ascorbic acid (AA) on the metabolic fate of iproniazid (IPN) and on the free radical intermediates derived from IPN were investigated in rats. After oral administration of IPN with or without AA, the plasma concentration and the urinary excretion of IPN and its metabolites were determined by gas chromatography-mass spectrometry using stable isotope labeled compounds as internal standards. In the excretion of IPN and its metabolites except hydrazine (Hy), the differences between co-administration and single administration were not observed. The excretion of Hy, which is a known hepatotoxic metabolite, decreased clearly in the co-administration of IPN and AA. When IPN and AA were co-administered orally, the profiles of plasma levels of IPN and its metabolites were almost similar after the administration of IPN alone. Furthermore, no differences between i.v. co-administration and i.v. administration alone were observed. These results indicated that AA did not affect both absorption and metabolism of IPN. By the electron spin resonance (ESR) spectroscopy and spin-trapping technique, the ESR signals due to the alpha-(4-pyridyl 1-oxide)-N-tert-butylnitrone (4-POBN) adducts induced by isopropylhydrazine (IP-Hy) were two-fold higher than those by IPN in microsomal systems. The free radical formations of IPN and IP-Hy were significantly inhibited by AA in a dose dependent manner. The 4-POBN-trapped radical species generated from IPN and IP-Hy were presumed to be an isopropyl radical by the results of mass spectrometry.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Long-term follow-up study of three patients with the long QT syndrome.

We studied three women with the long QT syndrome. They were aged 42, 52 and 25 years and had experienced recurrent syncopal attacks. We followed case 1 for 17, case 2 for 18, and case 3 for over 6 y. The attacks tended to occur during the premenstrual stage in case 1 and case 2; case 3 often experienced attacks after exercise. The QT(U)c intervals on admission were 0.68, 0.62, and 0.50 in case 1, 2, and 3, respectively. Torsade de pointes followed by ventricular fibrillation was documented in case 1 and case 2. Although each was treated with a beta-blocker, none was fully compliant with the regimen. In case 1, estrogen therapy administered to maintain the hormonal balance premenstrually effectively prevented attacks. Despite the inconsistent use of beta-blockers, the attacks in case 1 and case 2 tended to decrease with age. Case 2 experienced no attacks after menopause. Cause 3 took medication consistently and remained free of attacks for over 6 y. Although she discontinued beta-blocker therapy because of pregnancy, she has experienced no attacks to date. These case studies suggest that hormonal status may be important in the development of syncopal attacks in female patients with the long QT syndrome.

Adult↗

Myocardial Na+ during ischemia and accumulation of Ca2+ after reperfusion: a study with monensin and dichlorobenzamil.

The intracellular cation contents were determined in isolated perfused rat heart using cobaltic EDTA as a marker of the extracellular space. In hearts in which Na+ accumulation was induced with monensin, a Na+ ionophore, during 20 min-ischemia which otherwise did not result in accumulation of Na+, the levels of Na+ and Ca2+ were significantly higher after reperfusion with a significant decrease in K+. While the recovery of the cardiac mechanical function (CMF) was complete after reperfusion in control hearts, the recovery was incomplete in monensin-hearts. Dichlorobenzamil (DCB), the most specific inhibitor of Na(+)-Ca2+ exchanger, infused for 10 min before induction of ischemia in a dose of 10(-5) M, which produced a definite suppression of CMF (over 80%), inhibited the accumulation of Ca2+ and Na+ and the loss of K+ and ATP after 40 min-ischemia and reperfusion. The same dose of DCB given for 3 min before induction of ischemia and after reperfusion, which produced a less than 20% inhibition of CMF, failed to prevent the Ca2+ accumulation after 40 min-ischemia and reperfusion. These findings are at variance with the idea that the accumulation of Na+ during ischemia and the consequent augmented operation of Na(+)-Ca2+ exchange is responsible for accumulation of Ca2+ after reperfusion.

Adenine Nucleotides↗

Antitumor activity of Toxoplasma lysate antigen against methylcholanthrene-induced tumor-bearing rats.

Growth of the tumor autoinduced by 20-methylcholanthrene (MC) in rats was inhibited after administration of Toxoplasma lysate antigen (TLA). The antitumor activity of TLA was most obvious in the early stage of tumoral growth. When TLA was administered to rats before the appearance of tumour, tumor formation was delayed slightly. Histopathological studies revealed dense growths of spindle tumor cells in untreated control rat, while enlarged central necrosis with the infiltration of lymphocytes and neutrophils was apparent in TLA-treated rats. According to the immunohistological examination of tumor tissue with anti-Thy-1 antibody, the rats treated with TLA showed large Thy-1 positive granular cells, whereas the untreated rats indicated only a few small Thy-1 positive cells. These observations indicate that TLA is a useful modifier of biological responses to MC-induced tumors.

Animals↗

Role of adherent spleen cells in the induction of cytotoxic activity by Toxoplasma lysate antigen.

In order to identify mechanisms responsible for the anti-tumor effects of Toxoplasma lysate antigen (TLA), we used an in vitro 51Cr release assay to study the functional properties of plastic-adherent cells during induction of splenic cytotoxic activity by TLA. Cytotoxic activity of non-adherent cells was measured in all experiments after a 6 days incubation. Induction of cytotoxic non-adherent cells by TLA required the presence of plastic-adherent spleen cells. In contrast, rhIL-2 alone was able to induce transformation of cytotoxic non-adherent cells from non-adherent spleen cells. Contact between adherent and non-adherent spleen cells was necessary for successful induction of cytotoxic non-adherent cells by TLA. Treatment of spleen cells with anti-macrophage serum prevented induction of cytotoxic activity by TLA. Biologically active IL-2 was not detected in culture supernatants of spleen cells exposed to TLA. These findings suggest that contact between TLA-sensitized non-adherent cells and macrophages is necessary for induction of cytotoxic cells in the presence of TLA. This contact, however, is not necessary for generation of IL-2-induced killer cells.

Animals↗

Therapeutic effects of Toxoplasma lysate antigen on 20-methylcholanthrene-induced BALB/c mouse tumors.

Therapeutic effects of Toxoplasma lysate antigen (TLA) were studied in mice bearing the tumor in the second passage of 20-methylcholanthrene (MC)-induced tumor cells. Intramuscular administration of TLA 7 days after the tumor-cell inoculation caused apparent inhibition of the tumor growth on day 14. The second treatment facilitated the therapeutic effects. Intravenous transfer of spleen cells prepared from TLA-sensitized mice into tumor-bearing mice also represented the growth inhibitory effects. Prominent effects were seen when the transferred cells were prepared 5 days after sensitization of donor animals. The inhibitory effects were absent in the groups transferred only the adherent cells or the non-adherent cells prepared from sensitized mice. The strongest inhibitory effect was observed in the group to which both adherent and non-adherent spleen cells were transferred simultaneously from sensitized mice. In in vitro experiments, spleen cells obtained from sensitized mice showed cytolytic effect on P-815 or YAC-1 cells after the secondary stimulation in vitro with TLA. Large non-adherent cells containing densely packed granules were induced when cultured with the adherent cells obtained from sensitized mice. These results revealed that TLA can inhibit the growth of the chemically-induced transplantable tumors by activation of adherent and non-adherent spleen cells.

Animals↗

Characteristics of cytotoxic cells induced by Toxoplasma lysate antigen in mouse spleen.

Spleen cells from Toxoplasma lysate antigen (TLA)-sensitized BALB/c mice showed the strong cytotoxic activity against both natural killer (NK)-sensitive cells (YAC-1 and RL male-1) and NK-insensitive cells (P-815), when incubated with TLA or recombinant human IL-2 (rhIL-2). The increment of TLA concentration in culture medium increased the cytotoxic activity. Treatment of effector cells; spleen cells from TLA-sensitized mice incubated with TLA, with anti-asialo GM1 or anti-Thy-1 plus complement inhibited the cytotoxic activity of effector cells, whereas treatment with anti-mouse Lyt-2.2 serum plus complement had no effect on the cytotoxic activity. Treatment of spleen cells from TLA-sensitized mice with anti-asialo GM1 and/or anti-Thy-1 plus complement inhibited cytotoxic activities of effector cells. These results suggested that spleen cells sensitized with TLA both in vivo and in vitro were asialo GM1 positive and Thy-1 positive, and the majority of cytotoxic cells induced by TLA were similar to lymphokine-activated killer (LAK) cells induced by IL-2.

Animals↗

Health profiles of workers exposed to acrylonitrile.

The objective of this study was to reveal the health effects of acrylonitrile (AN) in seven Japanese acrylic fiber manufacturing factories. The study subjects were 157 AN-exposed male shift workers who had been exposed to AN for 17 years on the average and 537 control workers whose working conditions were similar to those of the AN-exposed workers. The seven factories were classified into two groups according to their AN exposure levels in 1987, and also into three groups on the basis of 1976 exposure levels. The most highly exposed group of subjects showed a mean AN concentration of 1.13 ppm by personal sampling. Medical examination failed to detect any health effects attributable to long-term exposure to AN, although the existence of some symptoms of acute irritation could not be completely ruled out. The results of this study may provide a "no observed effects level" for human on-the-job exposure with regard to the health effects examined here.

Acrylonitrile↗