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Biomedical subjects

S Nakai

Publications and source records attributed to S Nakai.

At least 19 recordsLinked to original sources
PubMed1996

First evidence for accumulation of protein-bound and protein-free pyrraline in human uremic plasma by mass spectrometry.

Glucose-derived advanced glycation end products (AGEs) cross-link proteins and cause various biological tissue damage. One of them, pyrraline [epsilon-2-(formyl-5-hydroxymethyl-pyrrol-1-yl) -L-norleucine], has been demonstrated by utilizing antibody to accumulate in plasma and sclerosed matrix of diabetic individuals, suggesting responsibility for diabetic complications. To elucidate the involvement of pyrraline in uremia, we examined the pyrraline levels in patients with chronic renal failure by a mass spectrometric approach. Here we show that protein-free pyrraline as well as pyrraline with binding protein are significantly increased in non-diabetic uremic plasma compared to healthy subjects. Our results suggest that circulating pyrraline could be a substance contributing to complications in uremia.

Blood Proteins↗
PubMed1996

The Mfd protein of Bacillus subtilis 168 is involved in both transcription-coupled DNA repair and DNA recombination.

Inactivation of Bacillus subtilis orf1177 in an otherwise Rec+ strain reduced genetic exchange and DNA repair. When the mutation was transferred into a set of recombination-deficient and repair-deficient strains, the DNA repair and recombination ability of the double or triple mutant strains was drastically reduced. B. subtilis Orf1177 protein shares substantial homology with the Escherichia coli Mdf, RecG and UvrB proteins. In vivo analysis of UV-induced mutations suggests that Orf1177 is necessary for strand-specific DNA repair, as is the case for the E. coli MFD protein. Therefore, orf1177 and Orf1177 were termed mfd gene and Mfd protein, respectively. The purified Mfd protein has a native molecular mass of 140 kDa (expected molecular mass 133 kDa). The Mfd protein is a sequence-independent DNA binding protein with weak ATPase activity. The Mfd protein was able to displace in vitro B. subtilis or E. coli RNA polymerase stalled at a lesion. Therefore, Mfd protein appears to target the transcribed strand for repair by recognizing a stalled RNA polymerase and dissociating it from the DNA. In addition, the strong recombination-deficient phenotype of mfd- rec- strains suggest that Mfd protein is involved in homologous DNA recombination.

Amino Acid Sequence↗
PubMed1996

Alteration of numerical chromosomal aberrations during progression of colorectal tumors revealed by a combined fluorescence in situ hybridization and DNA ploidy analysis of intratumoral heterogeneity.

To trace the sequence of numerical chromosomal aberrations during tumor progression of colorectal tumors, we studied intratumoral heterogeneity of chromosomal copy number by a combined fluorescence in situ hybridization (FISH) and ploidy analysis. We used six formalin-fixed paraffin-embedded tumors of which the mucosal lesions were preserved. Nuclear suspensions were made from the tumor tissues that were scraped from several small regions in 100 micron thick sections. Copy number of chromosomes 1, 7, 17, and 18 were examined by FISH with centromeric repetitive probes. DNA ploidy was monitored by cytofluorometry, and was correlated to the chromosomal copy number on the smear slides of identical nuclear suspension from each tumor portion. All the tumors examined included the DNA-diploid regions in the mucosa, where cancer cells commonly showed monosomy 18 and/or trisomy 7. These chromosomal changes may be quite common early events before the occurrence of DNA-aneuploidy in the development of colorectal tumors. Three out of the 6 tumors included near-tetraploid (3.6-4.1C) cells in deeper invasive regions. Chromosomal constitution of DNA-aneuploid cells was suggested to derive from that of DNA-diploid cells through ploidy duplication with or without additional loss or gain of chromosomes.

Centromere↗
PubMed1996

Alternate repetition of short fore- and backfiltrations reduces convective albumin loss.

An effective therapeutic means to remove relatively large polypeptide uremic toxins seems to be a hemofiltration (HF) or hemodiafiltration (HDF) employing a larger-pore membrane, that is, a protein-permeable membrane. With either method, however, a significant amount of albumin will be lost into the ultrafiltrate or dialysate. Now, repetition of alternate short fore- and backfiltrations may prevent the development of the ultrafiltration-induced higher albumin concentration on the membrane surface (protein concentration polarization), where a single forefiltration time is shorter than the time needed for completion of protein concentration polarization. Since the albumin concentration on the protein-permeable membrane surface will be one of the determinants of albumin loss by convection, such HDF treatment may reduce protein loss into the dialysate. To examine this assumption, we alternately repeated short and rapid fore- and backfiltrations (push/pull HDF) through a protein-permeable membrane, each less than 1 second in duration and at each filtration volume of 15 ml, where a pyrogen-free dialysate was supplied. The present results indicated that the albumin amount lost by push/pull HDF was approximately one-third of that by conventional HDF. Nevertheless, the reduction rates of beta 2-microglobulin and myoglobin were significantly greater by push/pull HDF than by conventional HDF.

Blood Proteins↗
PubMed1996

Advantage of monitoring skin vibration as an index of arteriovenous fistular blood flow.

Monitoring of the skin vibration is disturbed little by environmental noise. Therefore, the skin vibration is more relevant than bruit on the skin by means of monitoring the fistular blood flow. Frequency analysis of the skin vibration generated by an internal arteriovenous fistula indicated two peaks of power spectral density (PSD), one in the frequency range of 4-10 Hz and the other from 100-300 Hz. The analysis of the skin vibration generated by an external fistula, however, showed only one peak in the range of 4-10 Hz and a moderate flat PSD level in the range of 100-300 Hz. The PSD level in the range of 100-300 Hz decreased dramatically or disappeared when the fistular blood flow diminshed or ceased. Therefore, the optimal frequency for monitoring skin vibration may be the range of 100-300 Hz.

Arteriovenous Fistula↗
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↗
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↗