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Biomedical subjects

K Nakano

Publications and source records attributed to K Nakano.

At least 253 records · Page 14Linked to original sources
PubMed1997

Advanced glycation end products induce expression of vascular endothelial growth factor by retinal Muller cells.

Recent studies have suggested that advanced glycation end products (AGEs) are involved in the development of diabetic complications. To assess the pathogenic role of AGEs and vascular endothelial growth factor (VEGF) in the development of retinal neovascularization in diabetic retinopathy, we investigated the effect of AGEs on induction of VEGF by retinal Muller cells and measured AGE and VEGF concentrations in the vitreous of patients with proliferative diabetic retinopathy (PDR) and nondiabetic patients. The expression of VEGF mRNA and the production of VEGF protein by cultured Muller cells were enhanced by the presence of AGEs. The vitreous concentrations of AGEs and VEGF were both elevated in patients with PDR compared with patients without diabetes (P < 0.01). There was a moderate positive correlation between the levels of crossline and VEGF (r=0.698, P < 0.01). Elevation of AGEs in the vitreous may promote intraocular neovascularization in diabetic retinopathy through production of VEGF from Muller cells.

Aged↗
PubMed1997

Scanning force microscopy of the interaction events between a single molecule of heavy meromyosin and actin.

How close an approach is necessary for two interactive protein molecules to recognize each other before association? How strong a force field is exerted between two proteins at the recognition distance? How extensive are the association interfaces? How strong a force is necessary to pull the associated proteins apart? By means of atomic force microscopy at a truly single molecule level, these fundamental and intriguing questions were answered with the muscle proteins actin and myosin.

Actins↗
PubMed1997

Estrogen-excitable forebrain projections to the ventral premammillary nucleus of the female rat.

Retrograde labels by Nuclear Yellow from the female rat ventral premammillary nucleus (PMv) were most numerous in the lateral septum (LS) and the preoptic area (POA) and spread laterally into the substantia innominata. Other labels were in the diagonal band nucleus, the substantia innominata and the bed nucleus of the stria terminalis. Constant-current, single-pulse electrical stimulation of the PMv in urethane-anesthetized ovariectomized rats elicited antidromic action potentials in the cingulate cortex, in addition to the structures that contained labeled neurons. In the LS or cingulate cortex, but not in the POA, estrogen decreased antidromic activation thresholds and shortened refractory periods. The PMv is a way station that relays estrogen-excitable septal, but not preoptic, effects. The PMv also contains fibers of passage that originate in estrogen-excitable cingulate neurons.

Animals↗
PubMed1997

Ca2+ flow via tunnels in polarized cells: recharging of apical Ca2+ stores by focal Ca2+ entry through basal membrane patch.

Intracellular Ca2+ store depletion induces Ca2+ entry across the plasma membrane, allowing the store to recharge. In our experiments, Ca2+ stores in pancreatic acinar cells were depleted by acetylcholine (ACh) stimulation in Ca2+-free solution. Thereafter, Ca2+ entry was only allowed through a CaCl2-containing pipette attached to the basal membrane. Recharging intracellular Ca2+ stores via a patch pipette occurred without a rise in the cytosolic Ca2+ concentration and depended on the operation of a thapsigargin-sensitive Ca2+ pump. After a period of focal Ca2+ entry, ACh could again evoke a rise in the cytosolic Ca2+ concentration, and this rise always started in the apical secretory pole. Recharging the apical Ca2+ store therefore depends on Ca2+ flow through a tunnel from the basal to the secretory pole, and the endoplasmic reticulum Ca2+ pump is essential for this process.

Acetylcholine↗
PubMed1997

Antibodies to glutamic acid decarboxylase in Japanese diabetic patients with secondary failure of oral hypoglycaemic therapy.

Some patients with non-insulin-dependent (Type 2) diabetes mellitus (NIDDM) are positive for antibodies to glutamic acid decarboxylase (anti-GAD), which have been shown to be a useful marker for the diagnosis and prediction of insulin-dependent (Type 1) diabetes mellitus (IDDM). Anti-GAD positive NIDDM patients tend to develop insulin deficiency. We investigated the prevalence of anti-GAD in 200 NIDDM with secondary failure of oral hypoglycaemic therapy (SF) and 200 NIDDM well controlled by diet and/or sulphonylurea agents (NSF). Twenty-two of 200 (11%, p < 0.05) SF patients and 6 of 200 (3%) NSF patients were anti-GAD positive. The positive. The positive rate for anti-GAD was as high as 23.8% in the non-obese and insulin deficient SF patients. The SF patients with anti-GAD tended to be non-obese and to have an impaired release of endogenous insulin. The internal before development of secondary failure was not associated with the presence of anti-GAD in this study. In conclusion we found that anti-GAD was positive in as many as 11% of the SF patients, suggesting that autoimmune mechanisms may play an important role in the pathogenesis of secondary failure or sulphonylurea therapy.

Analysis of Variance↗
PubMed1997

Diagnostic significance of antibodies to glutamic acid decarboxylase in Japanese diabetic patients with secondary oral hypoglycemic agents failure.

Some non-insulin-dependent diabetes mellitus (NIDDM) patients are positive for antibodies to glutamic acid decarboxylase (anti-GAD), and they tend to develop insulin deficiency. The aim of this study was to evaluate the prevalence of anti-GAD in NIDDM with secondary failure of sulfonylurea agents (NIDDM-SF) and to investigate the diagnostic significance of seropositivity for anti-GAD in NIDDM-SF patients by evaluating human leukocyte antigen (HLA)-DRB1 alleles concurrently. The prevalence of anti-GAD in NIDDM-SF, NIDDM, and new-onset (within 1 year after onset) insulin-dependent diabetes mellitus (IDDM) was 9.3% (39/420), 3.1% (12/392), and 65.0% (13/20), respectively. Pancreatic beta cell function deteriorated in NIDDM-SF patients positive for anti-GAD. HLA-DRB1 allele typing revealed that NIDDM-SF patients positive for anti-GAD were significantly associated with DRB1*0901 (RR = 2.81, P < 0.01), which is one of the susceptible alleles to IDDM. Shorter interval before development of secondary failure and insulin deficiency were significantly associated with the presence of DRB1*0901 (P < 0.05) in NIDDM-SF patients positive for anti-GAD. In conclusion, nearly 10% of NIDDM-SF patients are positive for anti-GAD, suggesting that an autoimmune mechanism might play an important role in the pathogenesis of NIDDM-SF patients. In addition, a combination of serological marker (anti-GAD) and genetic marker (HLA-DRB1) is useful for predicting clinical course of NIDDM patients with secondary failure of sulfonylurea agents.

Adolescent↗
PubMed1997

Influence of acetic acid on the growth of Escherichia coli K12 during high-cell-density cultivation in a dialysis reactor.

High-cell-density cultivations of Escherichia coli K12 in a dialysis reactor with controlled levels of dissolved oxygen were carried out with different carbon sources: glucose and glycerol. Extremely high cell concentrations of 190 g/l and 180 g/l dry cell weight were obtained in glucose medium and in glycerol medium respectively. Different behaviour was observed in the formation of acetic acid in these cultivations. In glucose medium, acetic acid was formed during the earlier phase of cultivation. However, in glycerol medium, acetic acid formation started later and was particularly rapid at the end of the cultivation. In order to estimate the influence of acetic acid during these high-cell-density cultivations, the inhibitory effect of acetic acid on cell growth was investigated under different culture conditions. It was found that the inhibition of cell growth by acetic acid in the fermentor was much less than that in a shaker culture. On the basis of the results obtained in these investigations of the inhibitory effect of acetic acid, and the mathematical predictions of cell growth in a dialysis reactor, the influence of acetic acid on high-cell-density cultivation is discussed.

Acetic Acid↗
PubMed1997

Antitumor activity and low intestinal toxicity of S-1, a new formulation of oral tegafur, in experimental tumor models in rats.

S-1, a new oral antitumor agent, is composed of 1-(2-tetrahydrofuryl)-5-fluorouracil (Tegafur, FT), 5-chloro-2,4-dihydroxypyridine (CDHP) and potassium oxonate (Oxo) in a molar ratio of 1:0.4:1. FT which is a masked compound of 5-fluorouracil (5-FU) acts as an effector, while both CDHP and Oxo which do not have antitumor activity themselves act as modulators. In this study, the antitumor activity and intestinal toxicity of S-1 were investigated using experimental tumor models in rats, and compared with those of other oral fluoropyrimidines, namely 5-FU, FT, FCD (1 M FT/0.4 M CDHP) and UFT (combination of FT and uracil). In rats bearing subcutaneous Yoshida sarcoma, S-1 inhibited tumor growth at the lowest dose (ED50 value: S-1 5, UFT 22, FT 82, FCD 5, and 5-FU 19 mg/kg per day), and induced the least host body weight suppression, leading to the highest therapeutic index (TI) (S-1 4.5, UFT 1.4, FT 1.8, FCD 2.0, and 5-FU 1.4). S-1 also showed a higher therapeutic effect than UFT against AH-130 and Sato lung carcinoma. After administration of S-1 and UFT at equitoxic doses, S-1 showed a higher and more prolonged concentration of 5-FU than UFT both in plasma (AUC0-infinity: S-1 28 nmolh/ml, UFT 15 nmol.h/ml) and in tumor tissue (AUC0-infinity: S-1 95 nmolh/g tissue, UFT 52 nmolh/g tissue), leading to a higher 5-FU level incorporated into the RNA fraction (F-RNA level) in tumor tissue (AUC0-24: S-1 7.0 nmolh/mg RNA, UFT 4.3 nmolh/mg RNA) and 5-8% higher thymidylate synthase (TS) inhibition in tumor tissue at every time-point through 24 h. Compared with other oral fluoropyrimidines after administration of the maximal tolerable dose (MTD), S-1 caused the lowest rates of intestinal toxicities, such as diarrhea and occult blood in feces. S-1 also showed a higher antitumor effect on Yoshida sarcoma implanted intracolonically than UFT at an equitoxic dose (tumor weight: S-1 64 +/- 30 mg, UFT 133 +/- 52 mg; P < 0.05). These results suggest that CDHP, which is a potent inhibitor of 5-FU degradation, increases the antitumor activity of FT, and that Oxo, which is an inhibitor of 5-FU phosphorylation, locally protects the gastrointestinal tract from 5-FU-induced toxicity without decreasing the antitumor activity.

Animals↗
PubMed1997

Pulmonary autograft implantation in the dilated aortic annulus.

The application of the pulmonary autograft (Ross) procedure in the treatment of dilated aortic annulus is still controversial, because technical errors of implantation are more likely to occur as the host annular diameter increases. The Ross procedure was successfully employed in a 28-year-old woman with a dilated aortic annulus after simple annular plication. The annulus was plicated beneath the three commissures where the pulmonary autograft was subsequently attached. The diameter of the annulus was reduced from 32 to 26 mm. This technique may provide a number of advantages compared with aortic valve replacement, especially for women of child-bearing age.

Adult↗
PubMed1997

Surgical management of Behçet's aortitis: a report of eight patients.

BACKGROUND: Behçet's aortitis is one of the most severe manifestations of Behçet's disease. However, there have been few reports of this rare entity. This article we describe our experience with surgical treatment of Behçet's aortitis in 8 patients. METHODS: From May 1978 to February 1995, we operated on 8 patients with Behçet's aortitis. All patients were followed up for a total of 54.4 patient-years (mean, 6.8 years). RESULTS: There were no operative deaths, but 1 patient died in the hospital of ventricular fibrillation. Another death occurred as a result of pseudoaneurysm rupture 10 months after operation. Fourteen operations were performed on eight patients: a second operation was performed on four patients, and a third operation was performed on two patients. The translocated Bentall procedure, a modified Bentall procedure, was performed six times. One patient required a second operation for graft detachment, but the others have done well without further surgical intervention. Aortic valve replacement was performed six times, and three reoperations were needed after aortic valve replacement. CONCLUSIONS: The translocated Bentall procedure may be effective for Behçet's aortitis, but further investigation is necessary.

Adult↗
PubMed1997

High prevalence of mitochondrial diabetes mellitus in Japanese patients with major risk factors.

To identify diabetes mellitus caused by the mitochondrial gene substitution at genomic nucleotide pair 3243 (M3243A-->G) we selected 87 diabetic patients with high risk factors such as maternal inheritance and hearing loss. Total DNA was extracted from peripheral leukocytes, and mitochondrial DNA fragments containing M3243A-->G were amplified by polymerase chain reaction (PCR). The amplified fragments were digested with a restriction endonuclease Apa1 and analyzed by agarose gel electrophoresis. The incidence of the M3243A-->G mutation was 4.6% (four of 87) in diabetic patients with maternal inheritance and/or hearing loss. In a subgroup with both maternal inheritance and hearing loss, the incidence of the mutation was as high as 21.4% (three of 14). Cardiac disorders were also present in all four diabetic patients with the mutation. This study suggests that maternal inheritance and hearing loss are useful clinical findings to identify diabetic patients with the mutation, and that cardiac involvement is a high risk factor for the M3243A-->G mutation.

Adult↗
PubMed1997

Troglitazone (CS-045) ameliorates albuminuria in streptozotocin-induced diabetic rats.

We studied the effect of troglitazone, a new oral antidiabetic agent that potentiates insulin action and reduces insulin resistance, on albuminuria in streptozotocin (STZ)-treated diabetic rats. Without affecting blood glucose level, blood pressure, and creatinine clearance, troglitazone treatment of diabetic rats significantly decreased the diabetes-associated albuminuria at all time points studied 14 to 12 weeks of treatment: diabetic 510 +/- 161 micrograms/24 h v diabetic treated 112 +/- 34 micrograms/24 h at 12 weeks, P < .05). These data suggest that troglitazone has potential in the treatment of diabetic nephropathy.

Albuminuria↗
PubMed1997

Stem cell factor in nasal polyposis and allergic rhinitis: increased expression by structural cells is suppressed by in vivo topical corticosteroids.

BACKGROUND: Mast cells are increased in nasal polyp (Np) and allergic rhinitis (AR) tissue and are suppressed by topical corticosteroid treatment. Stem cell factor (SCF), a mast cell growth and survival factor, may explain these phenomena. OBJECTIVE: We investigated structural cell gene expression and production of SCF in nasal tissues in patients who had received and who had not received in vivo intranasal corticosteroid therapy. METHODS: Northern blot analyses for messenger RNA and ELISA for biologically active SCF protein from cultured Np epithelial cells and fibroblasts were performed. Immunostaining for SCF in cultured and tissue nasal structural cells in the presence or absence of steroid treatment was also performed. RESULTS: We detected significant expression of SCF mRNA and protein by cultured Np epithelial cells and Np fibroblasts; Np fibroblast SCF supported the differentiation of mast cells in vitro. There were more immunoreactive SCF-positive Np epithelial cells in patients with AR than in control subjects (97.2 +/- 2.8 vs 45.6 +/- 22.0%; p < 0.0001). SCF that could be immunostained was significantly diminished overall in Np structural cells in the group given in vivo steroid treatment, with a modest (trend to significant) effect on any given cell type analyzed. In vitro treatment with budesonide of SCF-producing fibroblasts demonstrated inhibition of unstimulated, primary Np fibroblasts but not of IL-1-stimulated fibroblasts or transformed cell lines. CONCLUSIONS: Human Np and AR tissue structural cells express and produce increased SCF. Our in vitro studies suggest that intranasal steroids blunt SCF expression in Nps, an effect that may be responsible for a decrease in mast cells and symptoms.

Administration, Topical↗
PubMed1997

The small GTP-binding protein Rho1 is a multifunctional protein that regulates actin localization, cell polarity, and septum formation in the fission yeast Schizosaccharomyces pombe.

BACKGROUND: The small GTP-binding protein Rho has been shown to regulate the formation of the actin cytoskeleton in animal cells. We have previously isolated two rho genes, rho1+ and rho2+, from the fission yeast Schizosaccharomyces pombe in order to investigate the function of Rho using genetic techniques. In this paper, we report the cellular function of Rho1. RESULTS: We found that Rho1 is essential for cell viability and cell polarity using gene disruption and by exogenous expression of botulinum C3 ADP-ribosyltransferase. In cells expressing either a constitutively active Rho1 or a dominant-negative Rho1, actin patches were delocalized. Both the cell wall and secondary septum were thick and stratified in cells expressing the constitutively active Rho1, while the cell wall of cells expressing the dominant-negative Rho1 seemed to be loosely organized. Furthermore, inactivation of Rho1 is apparently required for the separation of daughter cells. Cell fractionation studies suggested that Rho1 is predominantly membrane-bound. Moreover, we observed that Rho1 is localized to the cell periphery and to the septum. CONCLUSIONS: Rho1 is involved in actin patch localization, the control of cell polarity, the regulation of septation, and cell wall synthesis.

ADP Ribose Transferases↗
PubMed1997

Sarin poisoning on Tokyo subway.

On the day of the disaster, 641 victims were seen at St. Luke's International Hospital. Among those, five victims arrived with cardiopulmonary or respiratory arrest with marked miosis and extremely low serum cholinesterase values; two died and three recovered completely. In addition to these five critical patients, 106 patients, including four pregnant women, were hospitalized with symptoms of mild to moderate exposure. Other victims had only mild symptoms and were released after 6 hours of observation. Major signs and symptoms in victims were miosis, headache, dyspnea, nausea, ocular pain, blurred vision, vomiting, coughing, muscle weakness, and agitation. Almost all patients showed miosis and related symptoms such as headache, blurred vision, or visual darkness. Although these physical signs and symptoms disappeared within a few weeks, psychologic problems associated with posttraumatic stress disorder persisted longer. Also, secondary contamination of the house staff occurred, with some sort of physical abnormality in more than 20%.

Adolescent↗
PubMed1997

Polymorphism of TAP1 and TAP2 in Japanese patients with rheumatoid arthritis.

Contribution of polymorphism of transporter associated with antigen processing 1 and 2 (TAP1 and 2) alleles to pathogenesis of Japanese rheumatoid arthritis (RA) was studied in 92 RA patients by PCR-RFLP. The allele frequency of TAP2A was slightly low (38.0%) and the frequencies of TAP2B and TAP2C were slightly high (39.7% and 17.9%) in RA, but these differences were not significant. These increases and decrease were due to the positive or negative associations with HLA-DRB1*0405. It was very likely that slight differences in TAP2A, TAP2B and TA2C in RA were secondary phenomenon reflecting an increase in HLA-DRB1*0405. The prevalence of TAP2E allele was low (3.3%, P < 0.01, Pc = not significant) and not correlated with HLA-DRB1*0405.

ATP Binding Cassette Transporter, Subfamily B, Mem↗