Biomedical subjects

H Iwahashi

Publications and source records attributed to H Iwahashi.

At least 19 recordsLinked to original sources

PubMed2007

Macrophages and dendritic cells infiltrating islets with or without beta cells produce tumour necrosis factor-alpha in patients with recent-onset type 1 diabetes.

AIMS/HYPOTHESIS: Type 1A diabetes results from autoimmune destruction of pancreatic beta cells. We examined the involvement of TNF-alpha and IL-1beta, as well as of T cells, macrophages and dendritic cells, in the destruction of beta cells in patients with recent-onset type 1 diabetes. MATERIALS AND METHODS: We obtained pancreatic biopsy specimens from six patients with recent-onset type 1 diabetes and analysed these by immunohistochemistry. RESULTS: T cell infiltration was less common in islets without beta cells (12.5 [0-33.3]%) than in those with beta cells (46.0 [17.4-83.3]%), while macrophages and dendritic cells showed a similar extent of infiltration into islets both with or without beta cells. TNF-alpha was detected in 25.0 (4.3-46.9)% of macrophages and 11.8 (0-40.0)% of dendritic cells infiltrating the islets in samples from each patient, but not at all in T cells. IL-1beta was detected in 1.8 (0-11.3)% of T cells infiltrating the islets with beta cells, while it was found in 19.2 (0-35.3)% of macrophages or 10.7 (0-31.3)% of dendritic cells infiltrating the islets in samples from each patient (all values median [range]). CONCLUSIONS/INTERPRETATION: Macrophages and dendritic cells infiltrate the islets and produce inflammatory cytokines (TNF-alpha and IL-1beta) during the development of type 1A diabetes.

Adolescent↗

PubMed2006

[Posterior ventricular septal perforation successfully repaired through right ventricular approach].

A 65-year-old man underwent a successful repair of a posterior ventricular septal perforation (VSP) 9 days after suffering an acute inferior myocardial infarction. After hospitalization, his hemodynamic condition gradually worsened, in spite of administering intensive medical therapy. Emergent operation was performed on the 4th day after onset. An equine pericardial patch was sutured around the VSP through the right ventricular side of the septum using the double-patch repair method and the right ventricular wall was closed as using the standard extracorporeal perfusion technique. The dimensions of the VSP measured 5 mm in diameter. Transesophageal echocardiography was performed on the 14th postoperative day. Cardiac catheter examination was done on the 18th postoperative day. No residual shunt was recognized and cardiac function was good. He was discharged on the 20th postoperative day. The occurrence of a posterior VSP is comparatively rare, and repair of VSP is difficult to perform during an acute period. Therefore, the operative results of VSP cases remain poor.

Aged↗

PubMed2005

Clinical and immunogenetic characteristics of fulminant type 1 diabetes associated with pregnancy.

OBJECTIVE: The objective of this study was to characterize the clinical and immunogenetic features of Japanese pregnancy-associated fulminant type 1 diabetes (PF). A group of patients with PF was compared with a group of patients of child-bearing age with fulminant type 1 diabetes that was not associated with pregnancy (NPF) in a nationwide survey conducted from 2000-2004. PATIENTS: The clinical characteristics of the 22 patients in the PF group were compared with those of the 48 patients in the NPF group. Human leukocyte antigen (HLA) class II DR and DQ genotyping of 17 PF and 20 NPF patients was performed. RESULTS: Arterial pH was significantly lower (P = 0.0366), and amylase values tended to increase in PF patients compared with NPF patients (P = 0.0515). In 22 PF patients, 18 developed disease during pregnancy (26.3 wk; range, 7-38), whereas four cases occurred immediately after delivery (10.5 d; range, 7-14 d). Twelve cases that developed during pregnancy resulted in stillbirth (67%), and five of the six fetal cases that survived were delivered by cesarean section. The haplotype frequency of HLA DRB1*0901-DQB1*0303 in PF was significantly higher than those in NPF (P = 0.0244) and controls (P = 0.0001), whereas that of DRB1*0405-DQB1*0401 in NPF was significantly higher than those in PF (P = 0.0162) and controls (P < 0.0001). CONCLUSIONS: The clinical symptoms of PF patients were more severe than those of NPF patients, and the prognosis of their fetuses was extremely poor. The type 1 diabetes-susceptible HLA class II haplotype is distinct in PF and NPF patients, suggesting that different HLA haplotypes underlie the presentation of PF or NPF.

Adolescent↗

PubMed2005

The biological effects of high-pressure gas on the yeast transcriptome.

The aim of the present study was to examine the feasibility of DNA microarray technology in an attempt to construct an evaluation system for determining gas toxicity using high-pressure conditions, as it is well known that pressure increases the concentration of a gas. As a first step, we used yeast (Saccharomyces cerevisiae) as the indicator organism and analyzed the mRNA expression profiles after exposure of yeast cells to nitrogen gas. Nitrogen gas was selected as a negative control since this gas has low toxicity. Yeast DNA microarray analysis revealed induction of genes whose products were localized to the membranes, and of genes that are involved in or contribute to energy production. Furthermore, we found that nitrogen gas significantly affected the transport system in the cells. Interestingly, nitrogen gas also resulted in induction of cold-shock responsive genes. These results suggest the possibility of applying yeast DNA microarray to gas bioassays up to 40 MPa. We therefore think that "bioassays" are ideal for use in environmental control and protection studies.

Feasibility Studies↗

PubMed2005

Pancreatic beta and alpha cells are both decreased in patients with fulminant type 1 diabetes: a morphometrical assessment.

AIMS/HYPOTHESIS: We have previously reported that fulminant type 1 diabetes is characterised by an absence of diabetes-related antibodies and a remarkably abrupt onset. However, little is known about the mechanism of beta cell destruction in this diabetes subtype, and to obtain insights into the aetiology of the disease, we investigated residual endocrine cells and the expression of Fas and Fas ligand in fulminant type 1 diabetes. METHODS: Residual beta and alpha cells were morphologically assessed in pancreatic tissue obtained by biopsy from five patients with recent-onset fulminant type 1 diabetes and five patients with recent-onset typical autoimmune type 1 diabetes. In addition, the expression of Fas and Fas ligand was evaluated by immunohistochemistry. RESULTS: In fulminant type 1 diabetes, beta and alpha cell areas were decreased significantly, compared with autoimmune type 1 diabetes and control subjects. In contrast, the alpha cell area was not decreased significantly in autoimmune type 1 diabetes, compared with that in control subjects. No Fas expression in islets and Fas ligand expression in CD3(+) cells in the exocrine pancreas were found in the fulminant type 1 diabetic patients who underwent this evaluation. CONCLUSIONS/INTERPRETATION: Our study showed that beta and alpha cells are damaged in fulminant type 1 diabetes. In addition to the lack of Fas and Fas ligand expression, the results suggest that the mechanism of beta cell destruction in fulminant type 1 diabetes is different from that in autoimmune type 1 diabetes.

Acidosis↗

PubMed2004

Effects of coffee consumption on oxidative susceptibility of low-density lipoproteins and serum lipid levels in humans.

Since little is known about how coffee intake affects low-density lipoprotein (LDL) oxidative susceptibility and serum lipid levels, we conducted an in vivo study in 11 healthy male students of Wakayama Medical University aged between 20 and 31 years fed an average Japanese diet. On days 1-7 of the study, the subjects drank mineral water. On day 7, the subjects began drinking coffee, 24 g total per day, for one week. This was followed by a one week "washout period" during which mineral water was consumed. Fasting peripheral venous blood samples were taken at the end of each one-week period. LDL oxidation lag time was approximately 8% greater (p < 0.01) after the coffee drinking period than the other periods. Serum levels of total cholesterol and LDL-cholesterol (LDL-C) and malondialdehyde (MDA) as thiobarbituric acid reactive substances (TBARS) were significantly decreased after the coffee drinking period. Finally, regular coffee ingestion may favorably affect cardiovascular risk status by modestly reducing LDL oxidation susceptibility and decreasing LDL-cholesterol and MDA levels.

Adult↗

PubMed2004

A yeast DNA microarray for the evaluation of toxicity in environmental water containing burned ash.

Numerous studies on the hazard assessment and epidemiological health responses to burned ash have been reported. However, there is little information on the potential toxicity of unknown chemical complexes in burned ash. For an overall evaluation of the multiple toxicities of burned ash, a DNA microarray was used in this study, as a new attempt to assess these toxicities. Using the global gene expression on yeast DNA chip to reflect the changes in mRNA levels, our study discovered a lot of evidences for the action of cell homeostasis and stress response etc., against the toxic effects on yeast cells. On the genes of 5,117 open reading frames (ORFs), as valid spots in a microarray, 997 were up-regulated, 1,259 were down-regulated and 2,861 remained unchanged. A detailed analysis of the microarray revealed the genes that were dynamically correlated to the function of the subcellular localization, energy/metabolism, various stress responses/cell homeostasis and detoxification. Significantly, the toxicities, caused by reactive oxygen species (ROS), metals and the other xenobiotics, were indicated in burned ash. Also, the possibility of mutagenicity of the burned ash was suggested on the basis of the DNA repair related genes.

Biomarkers↗

PubMed2004

Comprehensive gene expression analysis of the response to straight-chain alcohols in Saccharomyces cerevisiae using cDNA microarray.

AIMS: The purpose of this study was to examine the gene expression profiles of yeast Saccharomyces cerevisiae subjected to straight-chain alcohols. METHODS AND RESULTS: Lipophilic alcohols with high log Pow values were more toxic to yeast than those with low log Pow values. Morphological changes after exposure to ethanol, 1-pentanol, 1-octanol were observed, whereas n-pentane as a model hydrocarbon affected the surface of the outer membrane, with little change in organelles. Using cDNA microarrays, quite a few up-regulated gene categories were classified into the category 'cell rescue, defence and virulence' by ethanol, and the category 'energy' and 'metabolism' by 1-pentanol. Meanwhile, the characteristic genes up-regulated by n-pentane were not observed, and the expression profile was distantly related to ethanol, 1-pentanol and 1-octanol. CONCLUSIONS: This study suggests that gene expression profiles at the whole genome level were intimately associated with the cell growth inhibition and morphological changes by straight-chain alcohols with differing log Pow values. SIGNIFICANCE AND IMPACT OF THE STUDY: The study of comprehensive gene expression profiles by cDNA microarrays elucidates the straight-chain alcohol adaptation mechanisms.

1-Octanol↗

PubMed2003

Yeast pheromone signaling pathway as a bioassay to assess the effect of chemicals on mammalian peptide hormones.

The intercellular pheromone signal transduction pathways involved in sexual reproduction in the yeast Saccharomyces cerevisiae constitute an extracellular network system involving cell surface receptors. The system is analogous to the signaling pathway of mammalian peptide hormones. The yeast mating pheromone alpha factor is homologous to mammalian gonadoliberins such as luteinizing hormone-releasing hormone (LHRH). In this study, we used the yeast pheromone signaling pathway as a model system to evaluate the effect of industrial chemicals on mammalian peptide hormones. Haploid a- and alpha-cell types conjugate, using mating pheromones, to form diploid cells. However, in a cells treated with certain chemicals used in pesticides, fungicides, and industrial products (i.e., TPN (CAS No. 1897-45-6), thiuram (CAS No. 137-26-8), captan (CAS No. 133-06-2), oxine-copper (CAS No. 10380-28-6), zineb (CAS No. 12122-67-7), and ziram (CAS No. 137-30-4)) the induction of shmoo formation was suppressed even when commercial alpha-factor was added. The FUS1-lacZ gene, which is transcriptionally regulated by a pheromone, was transferred into yeast and the effects of TPN, captan, zineb, and ziram, under sublethal conditions, were investigated: beta-Galactosidase levels declined to levels similar to that of untreated control cells when in the absence of the alpha-factor. Furthermore, these chemicals influenced conjugation to alpha-cells, and mating efficiency declined as chemical concentration increased. Analysis of the yeast pheromone signaling pathway helps to establish chemical toxicity assay models for mammalian peptide signal transduction pathways.

Animals↗

PubMed2003

Plasma adiponectin levels in women with anorexia nervosa.

Adiponectin is a plasma protein exclusively secreted by adipose tissue, which plays a role in modulating lipid and glucose metabolism. The plasma adiponectin concentration shows an inverse correlation with the body mass index in normal and obese individuals, but it has not been investigated in subjects with an extremely low body weight and undernutrition such as anorexia nervosa patients. We investigated plasma adiponectin levels in 21 females with anorexia nervosa. Nineteen healthy females served as the lean control group. The subjects with anorexia nervosa had a significantly lower weight and showed a tendency towards higher adiponectin levels than the control group. No correlation between adiponectin and BMI was found in patients with anorexia nervosa, while a linear negative correlation was seen in lean controls. The patient who showed the lowest adiponectin level reached a life-threatening state and required intravenous feeding in hospital. In association with improved nutrition and weight gain, the adiponectin level increased gradually until the body mass index was about 16 and then decreased subsequently as would be expected in lean normal subjects. These observations suggest that adipose tissue secretes less adiponectin and the adiponectin levels do not show an inverse correlation simply with body mass index in some subjects with severe undernutrition.

Adiponectin↗

PubMed2002

[Coronary artery bypass grafting in the patients with renal dysfunction].

We studied coronary artery bypass grafting (CABG) in patients with renal dysfunction. From April 1994 to October 1999, 59 patients with renal dysfunction underwent CABG. The patients were divided into 2 groups: group A: 18 patients with end stage renal disease who were receiving hemodialysis, group B; 41 patients with creatinine levels higher than 1.5 mg/dl who were not supported by dialysis. We compared and analyzed the findings of there 2 groups. Regarding preoperative factors, the incidence of old myocardial infarctions, diabetes mellitus and old cerebral infarctions did not differ significantly between the 2 groups. Regarding perioperative factors, the incidence of the number of vessel diseases, emergency operations, operation times and blood transfusions did not differ significantly between the 2 groups. Regarding the post-operative course, the hospital mortality rates demonstrated low levels in 2 groups. The graft patency of group A was 95%, while it was 99% in group B. The post-operative in-hospital days was 24.8 days in the group A, while it was 30.1 days in the group B. No significant difference was observed between the 2 groups. As a results, post-operative hemodialysis was needed in 8 of the patients who underwent on-pump CABG from group A. The actual survival rates were 75.3% in group A and 84.3% in group B at 4 years. The cardiac event free rate for group A was 93.3%, while it was 97.5% in group B at 4 years. In conclusion, CABG may improve the post-operative outcome in renal dysfunction patients. In addition, the use of off-pump CABG is also considered to achieve a better renal function than on-pump CABG.

Aged↗

PubMed2002

[Comparison of the prothrombin levels between the patients with atrial fibrillation and patients with cardiac pacemaker implantation due to sick sinus syndrome during anticoagulation therapy with warfarin].

We measured the fully carboxylated prothrombin levels using the Carinactivase-1 (CA-1) test and thus compared prothrombin levels between patients having atrial fibrillation (Af) without pacemaking and those having sick sinus syndrome due to Af with cardiac pacemaker implantation during anticoagulation therapy with warfarin. Total plasma samples were assayed for the CA-1 test, the prothrombin time international normalized ratio (PT-INR) and the thrombotest (TT). This prospective randomized study was carried out on 641 samples obtained at the Fukuoka University Hospital Department of Cardiovascular Surgery between May 1997 and March 1999. The patients were divided into 2 groups consisting of: group A; 144 patients having sick sinus syndrome due to Af implanted with a cardiac pacemaker who were treated with warfarin, group B; 497 patients atrial fibrillation without pacemaking who were treated with warfarin. The prothrombin levels in each group were 65.5 +/- 25.2 and 76.1 +/- 47.7 micrograms/ml, respectively. The normal prothrombin levels of group A decreased more significantly than in group B. Therefore, the PT-INR and TT were not significantly different between groups A and B. The dose of warfarin in each group was 2.4 +/- 1.0 and 2.6 +/- 1.4 g/day, respectively. The dose of warfarin in group A therefore decreased significantly different more than in group B. In conclusion, the normal prothrombin levels of patients atrial fibrillation increased more significantly than patients having sick sinus syndrome due to Af implanted with a cardiac pacemaker.

Aged↗

PubMed2001

Ascorbate-induced high-affinity binding of copper to cytosolic proteins.

Copper chaperones are necessary for intracellular trafficking of copper to target proteins. This is probably because the milieu inside the cell has a large capacity for sequestering this metal. By fluorometry using a fluorescent Cu(II) chelator and by centrifugal ultrafiltration, we have studied copper binding of the whole cytosolic proteins from mouse brain and liver, and found that their binding capacity and affinity for copper were markedly increased by ascorbate. Brain cytosolic protein bound, with high affinity, 63 nmol of copper/mg, more than half of which was redox-inactive, as indicated by its inability to catalyze oxidation of ascorbate. Most of the bound copper was in the Cu(I) state, coordinating to thiol groups of protein. Cytosolic protein competed for copper more strongly than GSH when compared at their relative concentrations in tissues. The results taken together suggest that protein thiols of cytosol can strongly sequester copper.

Animals↗

PubMed2001

Contribution of Hsc70 to barotolerance in the yeast Saccharomyces cerevisiae.

The contribution of Hsc70 to barotolerance in logarithmic-phase cells of the HSC70 (ssb1 and ssb2) deletion mutant and in strains expressing the HSC70 gene on either a low- or a high-copy-number plasmid was studied. The deletion-mutant strain had higher thermotolerance and a slightly lower barotolerance than the control strain. The strain that expresses the HSC70 gene in high copy number had a higher barotolerance than the strain that expresses the gene in low copy number. These results suggest that Hsc70 contributes to barotolerance during exponentially growing conditions as does Hsp104 during heat-shock treatment.

Gene Deletion↗

PubMed2001

A possible mechanism of maxillofacial abscess formation: involvement of Porphyromonas endodontalis lipopolysaccharide via the expression of inflammatory cytokines.

In a previous study, we developed a specific monoclonal antibody against Porphyromonas endodontalis lipopolysaccharide, and demonstrated that this lipopolysaccharide was detected in bacterially infected root canal fluid. We suggest here that P. endodontalis lipopolysaccharide in the infectious materials plays a stimulatory role in maxillofacial abscess formation via the expression of inflammatory cytokines. Our epidemiological study showed that this lipopolysaccharide was detected in significant levels the infectious material of patients with periapical periodontitis and odontogenic abscesses. Interestingly, infectious material-induced expression of tumor necrosis factor-alpha, interleukin-1beta, or neutrophil chemoattractant KC genes in mouse macrophages, was significantly neutralized by monoclonal antibody against the lipopolysaccharide. In addition, we also detected a significant amount of tumor necrosis factor-alpha in the infectious material. These results suggest that P. endodontalis lipopolysaccharide plays an important role in the pathogenic mechanism of maxillofacial abscess formation via the expression of inflammatory cytokines.

Adolescent↗

PubMed2001

Bioassay of cadmium using a DNA microarray: genome-wide expression patterns of Saccharomyces cerevisiae response to cadmium.

DNA microarray technology enables genome-wide detection of cell response at the transcriptional level. We are planning to make bioassay systems that can detect environmental chemicals to screen for potential bioreactive agents. To develop a DNA microarray for our purposes, the changes in gene expression underlying the yeast stress response to cadmium were analyzed by a microarray of total mRNA. Cadmium is a potent cell poison known to cause oxidative stress by changing intracellular glutathione levels. We report here that not only the glutathione synthesis gene (GSH1) but also almost all transcripts of the enzymes involved in the sulfur amino acid metabolism, especially MET14 and MET17, were greatly induced after exposure to cadmium. While several common stress-responsive genes, such as HSP26, GRE1, HSP12, and DDR48, were up-regulated more than almost fourfold by cadmium, there were also 42 other genes up-regulated more than fourfold. Based on these results, we concluded that DNA microarrays are very useful instruments for creating new bioassay systems and finding genetic promoters of stress indicators.

Adaptation, Physiological↗

PubMed2001

Pancreatic biopsy as a procedure for detecting in situ autoimmune phenomena in type 1 diabetes: close correlation between serological markers and histological evidence of cellular autoimmunity.

To better understand the pathogenesis of type 1 diabetes, we have developed pancreatic biopsy under laparoscope for recent-onset type 1 diabetic patients. The patients included 29 acute-onset type 1 diabetic patients, 5 latent-onset type 1 diabetic patients, and 1 type 2 diabetic patient. Their median age was 28 years, and the duration of diabetes at the time of biopsy was approximately 3 months. In 31 of 35 patients, we could obtain the pancreas tissue by punching. No serious complications, such as heavy bleeding, peritonitis, or pancreatitis, have been experienced. Pneumoderma was observed in two patients, and abdominal dull pain had continued for 2 days in two patients. However, special treatment was not necessary for these complications. T-cell-predominant infiltration to islets (insulitis) and hyperexpression of major histocompatibility complex class I antigens on islet cells were the two major findings and were observed in 17 of 29 recent-onset type 1 diabetic patients. These findings could be regarded as evidence of immune attack against beta-cells, and their presence was closely correlated with the presence of either anti-GAD or anti-IA-2 antibodies (P = 0.02). In conclusion, pancreatic biopsy under laparoscope is a safe procedure without serious complications, according to our findings, for detecting in situ autoimmune phenomenon in recent-onset type 1 diabetic patients.

Adolescent↗

PubMed2001

Determination of plasma prothrombin level by Ca2+-dependent prothrombin activator (CA-1) during warfarin anticoagulation.

BACKGROUND AND AIM OF THE STUDY: The carinactivase-1 (CA-1) test is a new method for monitoring plasma prothrombin levels during warfarin anticoagulation therapy. METHODS: A total of 192 patients were allocated to two groups. Group A patients (n = 42) were controls (no warfarin); group B patients (n = 150) received warfarin. A Ca2+-ion and Boc-Val-Pro-Arg-pNA (a chromogenic substrate for thrombin) were added to 10-fold diluted plasma, after which prothrombin was activated with CA-1. Prothrombin levels were determined by measuring the extent of p-nitoroaniline liberation. RESULTS: The mean prothrombin level was 112.8 +/- 20.0 microg/ml in group A (Gaussian distribution), and 53.3 +/- 19.6 microg/ml in group B. In group B, correlations were found between the CA-1 test and prothrombin levels measured by prothrombin time (PT; r = 0.61, p <0. 01), PT-INR (r = 0.61, p <0.01), Thrombotest (TT; r = 0.57, p <0.01) and Hepaplastin test (HPT; r = 0.69, p <0.01). CONCLUSION: The CA-1 test represents a viable method of monitoring the coagulation system. CA-1 recognized the Gla-domain of prothrombin, and activated prothrombin. The CA-1 test required only 10 microl of diluted blood plasma, and took approximately 30 min to complete. The CA-1 test also measures prothrombin levels, correlates excellently with other tests for coagulation, and compares well with currently available methods for determining the efficacy of warfarin.

Aged↗