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Biomedical subjects

S Nakai

Publications and source records attributed to S Nakai.

At least 73 records · Page 4Linked to original sources

Application of polymannosylated cystatin to surimi from roe-herring to prevent gel weakening.

A recombinant glycosylated cystatin with a polymannosyl chain was added to roe-herring surimi for preventing gel weakening due to autolysis during cooking. Proteolysis of myosin heavy chain in the surimi was effectively suppressed while cooking at 90 degrees C for 20 min after preincubation at 40 degrees C for 30 min. The glycosylation of cystatin improved the stability against heating as well as proteolysis by cathepsin D. This process markedly improved the texture of the cooked surimi gel with gel strength 2.5 times that of unglycosylated control cystatin.

Animals↗

Combined treatments with Ninjin-youei-to (Ren-shen-yang-rong-tang) plus a suboptimal dose of prednisolone on autoimmune nephritis in MRL/lpr mice.

MRL/lpr mice suffer from a systemic lupus erythematosus-like autoimmune disease. We studied the effects of oral treatments with Ninjin-youei-to (NYT, Ren-shen-yang-rong-tang, 1000 mg/kg/day), a suboptimal dose (2 mg/kg/day) of prednisolone(PSL) and their combination on nephritis in MRL/lpr mice. Treatments with NYT or PSL alone inhibited the development of proteinuria and prolonged survival. The combined treatment reduced the incidence of proteinuria and prolonged survival. In histological analysis, NYT treatments decreased the degree of mesangial proliferative glomerulonephritis and infiltration of mononuclear cells in the kidneys. PSL treatment was effective in reducing periglomerular nephritis and vasculitis in addition to such effects as NYT and NYT plus PSL treatment was more effective than PSL alone. The active form of TGF-beta was reduced in NYT and PSL-treated mouse serum, and the combined treatments further suppressed it. However, the treatment with NYT alone did not induce a decrease in the latent form of TGF-beta. The effect of NYT can be assumed to be different from an immunosuppressive effect of PSL. Therefore, the combined treatment with NYT and PSL can be expected to be more useful for the therapy of autoimmune disease such as nephritis, compared with NYT or PSL alone treatments.

Animals↗

Effects of L-carnitine supplementation on muscular symptoms in hemodialyzed patients.

Various muscle symptoms are well recognized among patients on maintenance hemodialysis. Carnitine deficiency may be an important factor of dialysis-associated muscle symptoms, whereas high-dose L-carnitine supplementation may result in unphysiologically high plasma levels of carnitine and carnitine esters. We studied the effect of low-dose L-carnitine treatment (500 mg/d) on muscle symptoms, plasma carnitine fractions, and lipid profiles in 30 periodically dialyzed patients with muscular weakness, fatigue, or cramps/aches. After 12 weeks of L-carnitine treatment, about two-thirds of patients had at least some improvement in muscular symptoms, whereas carnitine fractions were normal or slightly above normal ranges, but lipid profiles showed no demonstrable changes. This study also showed the correlation between plasma-free carnitine deficiency and months on dialysis. These results suggest that prolonged low-dose L-carnitine treatment can improve dialysis-associated muscle symptoms by restoring carnitine tissue levels and washing out acyl moieties.

Administration, Oral↗

Peripheral deletion of gammadelta T cells in haemodialysis patients.

Many patients with end-stage renal disease have altered host defenses against infectious agents. We have demonstrated that T cells, which play an important role in the immunological response, may undergo apoptosis by the Fas system in uraemia. To elucidate whether gammadelta T cells, which function as a first defense against intracellular pathogens, are altered in number or characteristics in dialysis patients, surface expressions of TCR, LFA-1 and Fas antigen on peripheral T cells were examined by immunofluorescence analysis. We demonstrated that the proportions of peripheral gammadelta T cells are altered significantly in haemodialysis (HD) patients. Interestingly, there were marked differences in the levels of expression of LFA-1 and Fas antigen between the two types of T cells. Moreover, both the expression of LFA-1 and that of Fas antigen were enhanced significantly in HD patients compared with normal controls. These results suggest that circulating gammadelta T cells may be susceptible to activation-induced cell death in comparison with alphabeta T cells in uraemic environments.

Adult↗

Endothelium-independent relaxant effect of 5-hydroxytryptamine (5-HT) on the isolated rabbit facial vein.

The facial vein in several species has been shown to have unusual properties, including exhibition of spontaneous myogenic tone and relaxation to norepinephrine (NE). The present study was undertaken to characterize the relaxant effect of 5-hydroxytryptamine (5-HT) on the rabbit facial vein. An isolated ring preparation of the rabbit facial vein exhibited intrinsic tone when it was stretched and the spontaneous contraction continued for hours. 5-HT concentration-dependently relaxed facial veins exhibiting spontaneous contraction. The relaxation was not inhibited by rubbing the endothelium or by NG-nitro-L-arginine (10(-4) M), a nitric oxide (NO) synthase inhibitor. The 5-HT-induced relaxation was also unaffected by pretreatment with indomethacin (10(-5) M), a cyclooxygenase inhibitor, and propranolol (10(-6) M), a both beta-adrenoceptor and 5-HT18-receptor antagonist. In contrast, 5-HT-induced relaxation of the facial vein was concentration-dependently antagonized by methysergide (10(-7) M and 10(-6) M), a non-selective 5-HT1- and 5-HT2-receptor antagonist, but not by NAN-190 (10(-6) M) and SDZ-205,557 (10(-6) M), antagonists for 5-HT1A- and 5-HT4-receptors, respectively. A higher (10(-6) M), but not lower (3 x 10(-7) M) concentration of ketanserin, a 5-HT2-receptor antagonist, slightly inhibited the 5-HT-induced relaxation. These results indicate that 5-HT-induced relaxation is not due to indirect mechanisms mediated by NE released from the sympathetic nerve terminals, or by endogenous prostanoid and endothelium-derived relaxing factor (EDRF = NO) released from the vascular tissues, but due to a direct effect on the 5-HT receptors located on vascular smooth muscle cells. However, the subtype of 5-HT receptor that produces relaxation of the rabbit facial vein remains to be clarified.

Animals↗

Nonshivering thermoregulatory responses in trained athletes: effects of physical fitness and body fat.

We studied the difference of thermoregulatory responses between trained male athletes (TR, n = 9) and untrained men (UT, n = 7) during 60 min of cold exposure (15 degrees C) without shivering, and examined the effects of physical fitness and body fat on these responses. Mean skin temperature (Tsk), esophageal temperature (Tes), and skin conductance (Kb) were similar between TR and UT, and heat production (M) for TR increased significantly during exposure at 15 degrees C. The M at 15 degrees C correlated positively with maximal oxygen uptake and negatively with body fat (%BF), but not with Tes. The Kb correlated negatively with Tes and positively with Tsk. The %BF also correlated negatively with Kb and Tsk during exposure at 15 degrees C, and the slope of %BF vs. Tsk relationship was significantly steeper in TR than in UT. These results suggest that (1) body temperature is maintained by the reduction of skin conductance, and (2) heat insulation independent of body fat is enhanced in trained athletes during cold exposure without shivering.

Adipose Tissue↗

Estimated number of patients with chronic renal failure but not with end-stage renal disease in Japan: comparisons between two estimation methods.

We estimated the number of patients with chronic renal failure (CRF) but not with end-stage renal disease (ESRD) in Japan by two methods: a nationwide survey and an estimation using incidence rates of ESRD among CRF patients as well as the number of incident ESRD. The former estimated the number of patients with CRF but not with ESRD as 154,000 (95% confidence interval 139,000-168,000), while so did the latter as 142,000 (133,000-150,000). It follows that the number of CRF patients including ESRD could amount to more than 300,000, which would give a substantial impact on public health in Japan. Despite some own methodological issues in estimation, the two estimates were reasonably in good agreement: supporting their methodological validity in estimation, since sources of errors appeared to be quite independent of each other.

Adult↗

The complete genome sequence of the gram-positive bacterium Bacillus subtilis.

Bacillus subtilis is the best-characterized member of the Gram-positive bacteria. Its genome of 4,214,810 base pairs comprises 4,100 protein-coding genes. Of these protein-coding genes, 53% are represented once, while a quarter of the genome corresponds to several gene families that have been greatly expanded by gene duplication, the largest family containing 77 putative ATP-binding transport proteins. In addition, a large proportion of the genetic capacity is devoted to the utilization of a variety of carbon sources, including many plant-derived molecules. The identification of five signal peptidase genes, as well as several genes for components of the secretion apparatus, is important given the capacity of Bacillus strains to secrete large amounts of industrially important enzymes. Many of the genes are involved in the synthesis of secondary metabolites, including antibiotics, that are more typically associated with Streptomyces species. The genome contains at least ten prophages or remnants of prophages, indicating that bacteriophage infection has played an important evolutionary role in horizontal gene transfer, in particular in the propagation of bacterial pathogenesis.

Bacillus subtilis↗

Sequence analysis of the groESL-cotA region of the Bacillus subtilis genome, containing the restriction/modification system genes.

We have determined a 35-kb sequence of the groESL-gutR-cotA (45 degrees-52 degrees) region of the Bacillus subtilis genome. In addition to the groESL, gutRB and cotA genes reported previously, we have newly identified 24 ORFs including gutA and fruC genes, encoding glucitol permease and fructokinase, respectively. The inherent restriction/modification system genes, hsdMR and hsdMM, were mapped between groESL and gutRB, and we have identified two open reading frames (ORFs) encoding 5-methylcytosine forming DNA methyl transferase and an operon probably encoding a restriction enzyme complex. The unusual genome structure of few ORFs and lower GC content around the restriction/modification genes strongly suggests that the region originated from a bacteriophage integrated during evolution.

Amino Acid Sequence↗

Short-acting nifedipine and diltiazem do not reduce the incidence of cardiac events in patients with healed myocardial infarction. Secondary Prevention Group.

BACKGROUND: The administration of calcium antagonists to patients with healed myocardial infarction is a controversial treatment. This study was conducted to elucidate the effect of short-acting nifedipine and diltiazem on cardiac events in patients with healed myocardial infarction. METHODS AND RESULTS: A controlled clinical open trial of 1115 patients with healed myocardial infarction was carried out between 1986 and 1994. The patients included 595 who received no calcium antagonist, 341 who received short-acting nifedipine 30 mg/d, and 179 who received short-acting diltiazem 90 mg/d. The primary end points were cardiac events, which were defined as fatal or nonfatal recurrent myocardial infarction; death from congestive heart failure; sudden death; and hospitalization because of worsening angina, congestive heart failure, or premature ventricular contractions. Cardiac events occurred in 51 patients (8.6%) in the no-calcium-antagonist group and 54 (10.4%) in the calcium-antagonist group (odds ratio, 1.24; 95% CI, 0.83 to 1.85), demonstrating that the calcium antagonists did not reduce the incidence of cardiac events. Subgroup analysis revealed no beneficial effects of these drugs for reducing cardiac events in patients with such complications as hypertension or angina pectoris. CONCLUSIONS: This study showed that use of short-acting nifedipine and diltiazem in this postmyocardial infarction population was associated with a 24% higher cardiac event rate, but this strong adverse trend did not reach statistical significance.

Aged↗

Sequence analysis of the 36-kb region between gntZ and trnY genes of Bacillus subtilis genome.

Within the framework of an international Bacillus subtilis genome sequencing project, we have determined a 36-kb sequence covering the region between the gntZ and trnY genes. In addition to five genes sequenced and characterized previously, 27 putative protein coding sequences (open reading frame; ORF) were identified. A homology search for the newly identified ORFs revealed that six of them had similarities to known proteins. It is notable that new ORFs belonging to response-regulator aspartate phosphatase (Rap) and its regulator (Phr) families, and response regulator and sensory kinase families of two-component signal transduction systems have been identified. Furthermore, we found that some 180-bp non-coding sequence, that might be an remnant of an ancient IS element, is preserved in at least five loci of the B. subtilis genome.

Bacillus subtilis↗

Effects of administered route on tissue distribution and antitumor activity of polyethyleneglycol-coated liposomes containing adriamycin.

Tissue distribution, antitumor activity and side effects after intraperitoneal administration of polyethyleneglycol-coated liposomes containing adriamycin (PEG-LADR) were examined and compared to that after intravenous treatment. Plain liposomes (PLADR) and PEG-LADR appeared to maintain blood circulation by intraperitoneal injection and suggested usefulness in passive targeting. Because of the accumulation of ADR in the pancreas found after intraperitoneal treatment, this administered route of PLADR and PEG-LADR was expected to be useful as a method of targeting the pancreas. The side effects of ADR in the heart and liver were suppressed by the liposomalization and PEG-modification. The antitumor effect of ADR was increased by the liposomalization, and PEG-modification after intraperitoneal administration was superior to that after intravenous administration. The slowly disappearing pattern of PLADR and PEG-LADR from the abdominal cavity was similar. It is suggested that PLADR and PEG-LADR were absorbed intact from the abdominal cavity and transferred into the blood circulation.

Animals↗

lpr T cells have lower ability to maintain bcl-2 expression ex vivo.

Autoimmune-prone lpr mice develop lymphoproliferative disorders, whereas their lymphocytes show accelerated apoptosis in culture. To elucidate whether the bcl-2 protein, a repressor of apoptosis, is critical to the discrepancy between in vivo and in vitro survival, we examined bcl-2 expression in T cells from +/+ and lpr mice during culture. The expression levels of bcl-2 in cultured T cells from lpr mice were significantly down-modulated compared to those from +/+ mice and freshly obtained T cells. Besides, the reduction of bcl-2 protein levels was inhibited in T cells cultured in the presence of T cell receptor (TCR) signalling. These results suggest that lpr T cells might be susceptible to apoptosis in vitro due to down-modulation of bcl-2 by withdrawal of TCR signalling.

Journal Article↗

Survival in long-term haemodialysis patients: results from the annual survey of the Japanese Society for Dialysis Therapy.

The prognosis for haemodialysis patients is reported to be more favourable in Japan than in Europe or North America. Consequently, evaluation of the death predictors for haemodialysis patients in Japan is of considerable interest outside Japan. The Patient Registration Committee of the Japanese Society for Dialysis Therapy annually surveys the individual patient case mix, laboratory data and important events occurring in the previous years. Thus, using case mix data and laboratory data (including Kt/V and protein catabolic rate) from the 1993 questionnaire survey and the individual patients' life/death statistics from the 1994 questionnaire survey, a logistic regression analysis was conducted on 53867 patients. The analysis indicated that important death risk predictors were: (i) advanced age, (ii) occurrence of diabetes mellitus, (iii) male sex, (iv) Kt/V lower than 1.8, (v) haemodialysis time less than 5 h, (vi) protein catabolic rate less than 0.9 g/kg/day, and (vii) percentage body weight decrease less than 4% and more than 8% during the first haemodialysis session of the week.

Adult↗

Current status of renal replacement therapy in Japan: results of the annual survey of the Japanese Society for Dialysis Therapy.

Beginning in 1966, the Patient Registration Committee of the Japanese Society for Dialysis Therapy has conducted a survey once a year on renal replacement therapy in Japan. As of 1983, the survey covered the life/death of patients in the survey years, as well as the case mix of individual patients. In 1990 several laboratory variables were added to the survey items. The present report summarizes the data from the 1993 and 1994 surveys. The Committee mailed out questionnaire forms at the end of the survey year to the heads of all dialysis facilities. Survey forms were returned from 99.6% of the dialysis facilities in the 1993 survey, and from 99.8% of the facilities in the 1994 survey. Some 143709 patients were treated by renal replacement therapy in 1994 (7509 were treated by CAPD, and 131016 by extracorporeal haemopurification). The gross mortality rate was 9.5% in the same year. The mean values of the laboratory variables among 88693 patients undergoing thrice weekly haemodialysis were as follows in 1993: Kt/V, 1.31 +/- 0.30; protein catabolic rate, 1.04 +/- 0.30 g/kg/day; haemodialysis time, 4.12 +/- 0.50 h. In 1994, the variables were: predialysis serum creatinine concentration, 11.54 +/- 2.85 mg/dl; predialysis serum albumin concentration, 3.91 +/- 0.55 g/dl; predialysis haematocrit, 28.69 +/- 4.36%.

Aged↗