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Biomedical subjects

S Nakai

Publications and source records attributed to S Nakai.

At least 109 records · Page 6Linked to original sources
PubMed1996

Long-term nitrate treatment increases cardiac events in patients with healed myocardial infarction. Secondary Prevention Group.

BACKGROUND: Nitrates dilate coronary arteries, ameliorate myocardial ischemia, minimize left ventricular remodeling, and reduce mortality in patients with acute myocardial infarction. However, the effects of long-term treatment with nitrates on cardiac events in patients with healed myocardial infarction are not known. METHODS AND RESULTS: A total of 1,002 patients with healed myocardial infarction (789 male and 213 female) were randomly divided into 2 groups: treatment with nitrates or nontreatment. The mean observation period was 18.0 +/- 19.9 months. Primary end points were nonfatal and fatal recurrent myocardial infarction, death from congestive heart failure, and sudden death. Baseline characteristics of the 2 groups were also compared to determine any effects on outcome. Among the 621 cases treated with nitrates, 41 cases (6.6%) experienced cardiac events during the observation period, whereas only 12 of the 381 cases that were not treated with nitrates (3.1%) had cardiac events. This difference was statistically significant (p < 0.05; odds ratio 2.17; 95% confidence interval 1.13-4.19). There were no differences in the incidence of noncardiac death or being lost to follow-up between the 2 groups. Although the precise mechanism of this increase in the occurrence of cardiac events by long-term treatment with nitrates is not clear, nitrate tolerance with possible rebound and neurohormonal effects may be involved. CONCLUSION: Long-term treatment with nitrates increased cardiac events in patients with healed myocardial infarction.

Aged↗
PubMed1996

[Combined fluorescence in situ hybridization and cytofluorometric analysis of numerical chromosomal aberrations in squamous cell carcinomas of the tongue].

DNA cytofluorometry and fluorescence in situ hybridization (FISH) with centromeric repetitive probes of chromosomes 1, 7, 11, 17, X and Y were used to detect numerical chromosomal aberrations in 13 squamous cell carcinomas of the tongue. In 4 of the 6 DNA-diploid tumors examined, significant numerical aberrations in at least 1 of the chromosomes were detected. The main line of 1 tumor showed trisomy 1 and the other 3 tumors had significant sublines that showed trisomy or monosomy of the 1 or 2 chromosomes examined. No common specific aberrations were detected in these tumors. Cytofluorometrically we found polyploidy in all 4 of the tumors with numerical chromosomal aberrations. These results suggest that subpopulations which are aneuploid at the chromosome level arise preferentially from DNA-diploid tumors with polyploidy before the ploidy of the main line shifts to overt DNA-aneuploidy. In all of the 7 DNA-aneuploid tumors examined, we detected numerical chromosomal aberrations. Most of the aberrations were thought to occur after tetraploidization because a gain in chromosomal copy number including tetrasomy was common. In 3 DNA-aneuploid tumors, however, the main line showed disomy 11, whereas the other chromosomes examined had 3 or more copies. In 1 of the 3 tumors there was a significant subline of monosomy 11. In these 3 tumors disomy 11 may have been preceded by a DNA-diploid stage with monosomy 11 before tetraploidization.

Carcinoma, Squamous Cell↗
PubMed1996

Induction of differentiation and enhancement of vincristine sensitivity of human erythroleukemia HEL cells by vesnarinone, a positive inotropic agent.

We examined the effect of vesnarinone, an oral cardiotonic, on the growth and differentiation of human myeloid leukemia cells. Vesnarinone alone markedly induced erythroid differentiation of HEL cells. All-trans-retinoic acid also induced erythroid differentiation of the cells, and the differentiation was greatly enhanced by combined treatment with vesnarinone and retinoic acid. HEL cells are highly resistant to some anticancer drugs, including vincristine, but treatment with vesnarinone greatly increased the sensitivity of HEL cells to vincristine. Enhancement of vincristine sensitivity by vesnarinone was not as significant for other leukemia cells. Expression of P-glycoprotein in HEL cells was effectively inhibited by vesnarinone, suggesting that the restoration of vincristine sensitivity is associated with decrease of P-glycoprotein expression in HEL cells. The plasma level of vesnarinone required to induce differentiation of leukemia cells is 30 micrograms/mL, which could be achieved with oral administration. These results suggest that vesnarinone should be useful in differentiation therapy for some types of myelogenous leukemia.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

[Five cases of myelodysplastic syndrome treated with cytarabine ocfosfate].

Five cases of myelodysplastic syndrome were treated with cytarabine ocfosfate. Ocfosfate (100-200 mg) was orally administered for 14 days with 14 days' interval. Etoposide was combined in one case, and nartograstim was added in two cases. Two of the five cases achieved remission, one case having complete remission, and another case showing a good response. Their remission durations were 141 and 112 days, respectively. Further improvement of therapy is needed to achieve a higher remission rate and a longer remission duration.

Administration, Oral↗
PubMed1996

[A review of epidemiologic studies on the health effects of indoor environments].

Indoor bioaerosols (viruses, bacteria, dust mites, molds, etc.) have become the subject of discussion on indoor environments. A number of epidemiologic studies on the health effects of molds and home dampness, the latter being an important determinant of mold growth, have been conducted mainly in Europe and the United States. In this paper, a review of these epidemiologic studies is described. Questionnaires are used as the method of exposure assessment in most of the studies. The necessity for developing objective methods of dampness/mold exposure assessment has been expressed by some researchers. Respiratory symptoms, especially asthman attacks and wheezing for children, have been utilized in many investigations as a health effect index. Positive relationship between home dampness/mold and respiratory symptoms have been shown in numerous studies. Dampness and/or molds in dwellings may effect respiratory symptoms, but several problems for determining causal inference still remain: exposure assessment, temporal relationship, etc. While the differences in house structure and life style between Japan and Europe/U.S.A. should be considered, the health effects of home dampness and molds need to also be examined in Japan which is a country with high humidity levels.

Air Pollution, Indoor↗
PubMed1995

The POU domain transcription factor Brn-2 is required for the determination of specific neuronal lineages in the hypothalamus of the mouse.

We generated mice carrying a loss-of-function mutation in Brn-2, a gene encoding a nervous system specific POU transcription factor, by gene targeting in embryonic stem cells. In homozygous mutant embryos, migratory precursor cells for neurons of the paraventricular nuclei (PVN) and the supraoptic nuclei (SO) of the hypothalamus die at approximately E12.5. All homozygous mutants suffered mortality within 10 days after birth, possibly because of a complete deficiency of these neurons in the hypothalamus. Although neither developmental nor histological abnormalities were observed in heterozygous mice, the levels of expression of vasopressin and oxytocin in the hypothalamus of these animals were half these of wild-type mice. These results strongly suggest that Brn-2 plays an essential role in the determination and development of the PVN and SO neuronal lineages in the hypothalamus.

Animals↗
PubMed1995

Characteristics of antitumor activity of 3,4-dihydro-6-[4-(3,4-dimethoxybenzoyl)-1-piperazinyl]- 2(1H)-quinolinone (vesnarinone) against a human adenoid squamous carcinoma-forming cell line grown in athymic nude mice.

The tumors produced by transplantation into nude mice of human adenoid squamous carcinoma-forming cell line TYS, presumably derived from a minor salivary gland, were treated with a differentiation-inducing agent, vesnarinone, which was given per o.s. daily at a dose of 200 mg/kg for 35 days. They were then examined morphologically and immunohistochemically. The vesnarinone treatment resulted in a significant suppression of tumor growth. In addition, tumor nests indicating keratinocyte and acinar cell differentiation were often observed in the treated tumors, but not in untreated controls. Tissue sections from vesnarinone-treated and untreated TYS tumors were stained with monoclonal antibody (NAb) directed to carbohydrate antigen LeY or proliferating cell nuclear antigen (PCNA) and with rabbit polyclonal antibody to p53. Antibody staining patterns were compared with morphological characteristics of cells as revealed by hematoxylin and eosin staining, and DNA fragmentation patterns as revealed by 3'-OH nick-end labelling techniques. Tissue sections from vesnarinone-treated TYS tumors showed positive reaction with nick-end labelling and were extensively stained strongly by anti-LeY MAb, whereas the untreated tumors showed negative reaction with nick-end labelling and were infrequently stained by anti-LeY MAb. Within LeY-positive areas of tissue sections from the vesnarinone-treated tumors, keratinocyte and acinar cell differentiation as well as DNA fragmentation were frequently observed, although not all LeY-positive cells showed such signs of apoptosis. LeY-positive cells showed consistent negative staining by anti-PCNA MAb and anti-p53 rabbit serum. From these findings, it can be considered that vesnarinone has differentiation and apoptosis-inducing activity against TYS cells grown in athymic nude mouse.

Animals↗
PubMed1995

Effect of aerobic capacity on sweat rate and fluid intake during outdoor exercise in the heat.

We measured the aerobic capacity, sweat rate and fluid intake of trained athletes during outdoor exercise and examined the relationship between aerobic capacity and thermoregulatory responses at high ambient temperatures. The maximal aerobic capacity (VO2max) of the subjects, nine male baseball players of college age, was determined by maximal exercise tests on a cycle ergometer. The subjects practised baseball regularly without drinking fluids from 1330 to 1530 hours. After 30 min rest, they played a baseball game with free access to a sports drink at 15 degrees C from 1600 to 1830 hours. At a mean ambient temperature of 36.7 (SEM 0.2) degree C, the mean percentage of body mass loss (delta mb) and increase of oral temperature (delta To) from 1330 to 1530 hours was 3.47 (SEM 0.12)% and 0.81 (SEM 0.14) degree C, respectively. The sweat loss from 1330 to 1830 hours was 56.53 (SEM 1.56)ml.kg-1 of body mass (mb) while the mean fluid consumption was 44.78 (SEM 2.39)ml.kg-1 of mb, with recovery of 76.08 (SEM 2.81)% of sweat loss. The VO2max was significantly inversely correlated with delta mb, fluid intake and rehydration amount, but showed no correlation with delta To. These results would suggest that at a given exercise intensity in subjects with a higher aerobic capacity body temperature is maintained with a lower sweating rate than that in subjects with a lower aerobic capacity.

Adult↗
PubMed1995

New collateral flow increasing early after coronary occlusion prevented myocardial necrosis in dogs.

Increases in regional myocardial blood flow (Qm) developing soon after myocardial infarction may minimize myocardial necrosis. To test this hypothesis, Qm in the area surrounding an acutely occluded coronary artery was determined successively over 4 weeks in 11 dogs. Non-radioactive colored microspheres were injected into the left atrium 5 s (Qm at this time is referred to as Q1), 3 h (Q2), 12 h (Q3), and 4 weeks (Q4) after occlusion of the coronary artery. After termination of the experiment, the heart was removed, and Qm and three indices of myocardial necrosis i.e., myocardial creatine kinase activity (CK), infarct size determined by triphenyl tetrazolium chloride stain (TTC), and myocardial fibrosis visualized by Azan-Mallory stain, were determined. Each Qm was expressed as a percentage of normal: Qm (% of normal) = [Q/Qc] ischemic area/[Q'/Qc']non-ischemic area x 100, where Qc indicates Qm determined before coronary occlusion. In the ischemic area of the left ventricle, Q1, Q2, Q3, and Q4 were 25 +/- 3%, 30 +/- 3%, 31 +/- 3%, and 42 +/- 3% of normal, respectively, in the inner layer, and 31 +/- 3%, 52 +/- 4%, 52 +/- 4%, and 77 +/- 6% of normal, respectively, in the outer layers. During the 4-week period, the increase of Qm in the outer layer was greater than that in the inner layer. The inner layer showed a small increase of flow from Q3 to Q4 (9 +/- 2%), but in the outer layer there were greater flow increases from Q1 to Q2 (21 +/- 3%) and from Q3 to Q4 (24 +/- 6%).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Combined treatment with ren-shen-yang-rong-tang (Japanese name: ninjin-youei-to) plus prednisolone on adjuvant-induced arthritis in Lewis rat.

The effects of combined treatment with 250 mg/kg Ren-shen-yang-rong-tang (Japanese name: Ninjinyouei-to, NYT) plus 4 mg/kg, an average dosage, or 0.2 mg/kg, a suboptimal dosage, of prednisolone (PSL) on adjuvant-induced arthritis in Lewis rats were investigated using two treatment schedules. The agents were administered orally every day from day 0 to 21 (schedule A), or from day -7 to 21 (schedule B) after adjuvant injection. PSL treatment (4 mg/kg) obviously inhibited paw swelling due to non-immune inflammation, diminished the weights of the thymus, spleen, adrenals and iliac lymph nodes, and suppressed the increment of serum interleukin (IL)-6 concentration in both schedules compared to controls. NYT treatment alone inhibited paw swelling due to immune inflammation, diminished the weight of the adrenals and decreased IL-6 concentration only in schedule A. Combined treatment with NYT plus PSL (4 mg/kg) showed: (1) a superior effect to that of PSL on paw swelling in the uninjected hind foot, especially in schedule B, (2) a tendency to diminish adrenal weight in schedule A and the weights of all four organs in schedule B compared with PSL treatment alone, and (3) a suppressive effect on IL-6 concentration weaker than that of PSL alone in schedule B. The suppressive effect of combined treatment with NYT plus PSL (0.2 mg/kg) on paw swelling was significantly stronger compared with either NYT or PSL treatment alone in schedule B. Although this dose of PSL had no influence upon the IL-6 concentration, the combined treatment or NYT alone increased the IL-6 concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1995

Effect of bone marrow transplantation on antiphospholipid antibody syndrome in murine lupus mice.

The (NZW x BXSB)F1 (W/BF1) mouse is known to be an animal model of systemic lupus erythematosus (SLE) and immune thrombocytopenic purpura (ITP). These mice produce not only anti-DNA antibodies but also anti-platelet antibodies, resulting in decreased platelet counts. They show a high level of proteinuria, increased white blood cell (WBC) counts, hypertension, and myocardial infarction due to the high levels of anti-cardiolipin antibodies. When W/BF1 mice (4-5 months) were lethally irradiated and then reconstituted with T cell-depleted bone marrow cells of normal BALB/c mice (8 weeks), 60% of the mice survived more than one year. The WBC and platelet counts in the mice were normalized, and the levels of anti-DNA and anti-platelet antibodies decreased. The renal dysfunction was also ameliorated as indicated by a lower level of proteinuria, lower levels of serum creatinine (S-CRTN) and blood urea nitrogen (BUN), and by improved histology. The blood pressure (BP) of the treated W/BF1 mice decreased due to the improved renal functions. In contrast to the non-treated W/BF1 mice which died of myocardial infarction or renal failure by the age of 7 months, the treated W/BF1 mice showed no evidence of myocardial infarction even one year after BMT. This was due to the lower cardiolipin levels.

Animals↗
PubMed1995

The Bacillus subtilis dnaC gene encodes a protein homologous to the DnaB helicase of Escherichia coli.

Within the region of the Bacillus subtilis chromosome assigned to us in the genome sequencing project, we found a gene, the product of which is similar to the DnaB protein (replicative DNA helicase) of Escherichia coli. Three B. subtilis dna gene mutations, dnaC30 and ts56 causing defects in elongation and ts199 causing a defect in the initiation of replication, were mapped in the gene by transformation and DNA sequencing. Both dnaC30 and ts56 have been located near the amino-terminal end of the B. subtilis DnaC protein. In contrast, ts199 has been located near the carboxy-terminal of the protein. Our results indicate that the B. subtilis dnaC gene encodes a counterpart of the E. coli dnaB helicase.

Amino Acid Sequence↗
PubMed1995

Stimulatory effect of 1 alpha,25-dihydroxyvitamin D3 on mouse alveolar macrophage tumor necrosis factor-alpha production in vitro: involvement of protein kinase C and Ca2+/calmodulin-dependent kinase.

1 alpha,25-Dihydroxyvitamin D3 [1 alpha,25(OH)2D3, calcitriol] has been shown to modulate the immune function of peripheral monocytes and peritoneal macrophages. However, its effect on alveolar macrophage (AM) cytokine secretion has not been reported. We therefore investigated the influence of calcitriol on tumor necrosis factor (TNF-alpha) production by murine AMs and attempted to elucidate changes in the signal transduction system involved in such effects. Calcitriol significantly enhanced TNF-alpha secretion by AM stimulated with either lipopolysaccharide (LPS; 10 micrograms/ml; p < 0.005) or phorbol 12-myristate 13-acetate (PMA; 100 ng/ml; p < 0.05) at low doses (between 10(-11) and 10(-9) M). However the protein kinase C (PKC) inhibitor, H7 (10 microM), and the Ca2+/calmodulin inhibitor, W7 (25 microM), reversed such calcitriol effects. Calcitriol increased the total PKC activity of AMs. These findings indicate that calcitriol enhances both LPS- and PMA-stimulated TNF-alpha secretion through PKC- or Ca2+/calmodulin-dependent pathways.

Animals↗