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Biomedical subjects

M Igarashi

Publications and source records attributed to M Igarashi.

At least 145 records · Page 8Linked to original sources

Natural history and risk factors for immunoglobulin A nephropathy in Japan. Research Group on Progressive Renal Diseases.

The Research Group on Progressive Renal Diseases conducted a national survey, in Japan, of cases of primary glomerulonephritis (GN) in 1985 and 1993. The results of the survey, reported here, revealed a high prevalence and relatively poor prognosis for immunoglobulin A nephropathy (IgAN). Using immunofluorescent microscopy, 47.2% of 1,063 patients were diagnosed as having IgAN; 62.8% of patients had diffuse mesangial proliferative GN, and focal mesangial proliferative GN was observed in 23.0%. Nearly 70% of the patients had no clinical symptoms, and the IgAN was detected by routine physical examination. The mean period of observation was 11.8 +/- 6.3 years. Renal survival rates for the 502 cases of IgAN, in which the start of dialysis and renal-related death were end points, were 96%, 85%, 75%, and 61% at 5, 10, 15, and 20 years, respectively, from the time of the detection of the earliest known renal abnormalities. Renal survival rates of patients with diffuse mesangial proliferative GN were 96%, 83%, 75%, and 59% at 5, 10, 15, and 20 years, respectively. At the end of the observation period, 20% of patients had improved, 45.8% showed no change, 13.5% had deteriorated, and 20.4% had renal-related death. The risk factors for renal failure by logistic multivariate analysis were serum creatinine concentration > or =1.4 mg/dL (relative risk, 3.5) and levels of urinary protein > or = +(dipstick) (relative risk, 6.4), determined at the time of biopsy. These parameters can be useful for assessing prognosis during the relatively advanced stages of this disease. It is important to note that a relatively high percentage of patients with IgAN progressed to end-stage renal failure even when their histologic findings comprised only minor glomerular abnormalities or focal proliferative changes.

Adolescent↗

Cloning of chick cellular retinol-binding protein, type II and comparison to that of some mammals: expression of the gene at different developmental stages, and possible involvement of RXRs and PPAR.

We cloned chick cellular retinol-binding protein, type two (CRBP II) cDNA and compared it with those of some mammals. The deduced amino acid sequence showed that chick CRBP II was one amino acid greater in size than those of mammals, and the nucleotide sequence of chick CRBP II shared 72%-75% similarity with those of mammals. RNA blot hybridization analysis showed that CRBP II transcript of 0.7 kb was first detected in the duodenum of day-18 embryonic chick, and exhibited a rapid increase during 24 hr around the hatching. Northern blot hybridization also revealed that the transcripts of two types of retinoid X receptors (RXR alpha and RXR gamma) and peroxisome proliferator-activated receptor (PPAR) were expressed in the chick duodenum at hatching. The organ culture of day 16 embryonic chick duodenum showed that the addition of 9-cis retinoic acid in the medium caused a significant increase in CRBP II mRNA levels. In addition, arachidonic acid, from which putative ligands for PPAR were supposed to be generated, was accumulated around hatching in the duodenum. The results may suggest that the abrupt increase of the CRBP II gene expression in the chick duodenum around hatching may be related with RXRs and/or PPAR.

Animals↗

Moebius syndrome and central respiratory dysfunction.

Two infants, 18 months and 4 months of age, who were born with bilateral VI and VII nerve palsy (Moebius syndrome) experienced central respiratory failure requiring persistent ventilation. The computed tomography scan showed small brainstem tegmental calcifications. These findings suggest intrauterine brainstem necrosis including the respiratory center and poor prognosis for independent respiration.

Brain Diseases↗

Suppression of neointimal thickening by a newly developed HMG-CoA reductase inhibitor, BAYw6228, and its inhibitory effect on vascular smooth muscle cell growth.

1. The aim of this study was to determine whether BAYw6228 (BAYw), a newly developed 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitor, could suppress an atherogenic process such as intimal thickening by a mechanism other than lowering the level of serum cholesterol. 2. First, we evaluated the in vitro effect of BAYw on the proliferation of vascular smooth muscle cells (SMC) from various species: Sprague-Dawley (SD) rats. New Zealand (NZ) white rabbits, intimal cells from Watanabe hereditary hyperlipidemic (WHHL) rabbit and SMC from the new-born human aorta. The increasing rate of total protein content of these cells was inhibited by the addition of BAYw in a dose-dependent fashion. In the presence of 2% foetal calf serum (FCS), the value of IC50 was 1.0 microM in SD rats, 2.1 microM in NZ white rabbits, and 0.3 microM in WHHL rabbits. With human SMC, the value was 0.02 microM in the presence of 10% FCS and 0.2 microM with a mixture of growth factors. 3. Based on these above in vitro findings, we next examined the in vivo effect of the agent to determine whether it could suppress rabbit intimal thickening induced by balloon catheterization. A balloon catheter was inserted from a peripheral branch of the left external carotid artery to the aorta to denude the endothelium of the left common carotid artery in Japanese white rabbits. After 12 days they were divided into control and BAYw groups. The former were subcutaneously injected with saline and the latter with BAYw 1 mg kg-1 day-1. Two days after the beginning of treatment, a second balloon injury was performed to the previously injured left common carotid artery in both groups. After another two weeks, the left common carotid artery was removed and variously stained. Although the total serum cholesterol in the BAYw group was significantly lower than in the control (P < 0.05), the difference was not enough to affect intimal thickening. In addition, the BAYw group had a smaller intima/media ratio than the control group, decreasing to 45% of control (P < 0.05). By anti-alpha smooth muscle actin antibody staining, these intimal thickening areas were entirely occupied by SMCs, and their amount was attenuated by BAYw. By anti-rabbit macrophage antibody (RAM 11) staining, the number of positive cells in the intimal thickening was markedly decreased in the BAYw group compared to control (P < 0.01). 4. These results indicate that BAYw has an inhibitory effect on intimal thickening by attenuating intimal SMC proliferation and infiltration of macrophages, suggesting that BAYw could be effective in the prevention of the progression of atherosclerotic plaque-like restenosis after angioplasty.

Animals↗

Expression of follicle-stimulating hormone receptor in human ovary.

The gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), are key hormones in the regulation of ovarian function. The acquisition of FSH receptors during folliculogenesis is believed to be a key event in the subsequent development of the follicle. However, the binding and biochemical properties of the human FSH receptor are not well-characterized owing to the low abundance of these receptors and the limited availability of human tissue. The binding experiments show that, while the affinity of the FSH receptor does not change through the menstrual cycle, the total number of FSH receptors in the leading follicles increases by about two-fold at mid-follicular phase compared with those at other periods. Northern blot analysis was used to measure relative levels of FSH receptor mRNA, and in situ hybridization was used to localize FSH receptor transcripts. Northern blot analysis of human ovaries detected two transcripts (4.1 and 2.4 kb) for the FSH receptor. The FSH receptor mRNA was abundant in the preovulatory follicle, with expression decreased by about 50% in the corpus luteum. Using in situ hybridization, FSH receptor mRNA was found to be confined to the granulosa cells of developing follicles. A reverse transcription-polymerase chain reaction amplification was used to detect the expression of different isoforms of the FSH receptor mRNA in human corpus luteum and placenta.

Adult↗

A medical school for rural areas.

Jichi Medical School (JMS) was established in 1972 to supply graduates to rural areas where medical resources are scarce. JMS has several unique characteristics aimed at motivating graduates to work in a rural practice. These include financial aid for students, a home prefecture recruiting scheme, location in a non-urban area, management by prefectures and support from the national government. The achievements of JMS over the 24-year period since its foundation have been evaluated. A questionnaire has been mailed to all JMS graduates since the first year of graduation. Using a pro-active approach to follow-up, the return rate has been virtually 100%. The authors investigated annual changes in the distribution of the graduates as well as the present status of the graduates in 1995. At that time, JMS graduates were distributed all over Japan. Among the 1871 graduates, 792 (42%) were working in rural areas in 1995. Nine-hundred and twenty-four graduated in the period from the first to the ninth output of graduates. Among these, 858 (93%) completed the requisite 9 years of work contracted between JMS and the graduates, 620 (67%) had practised in the same prefecture, and 305 (33%) were still practising in a rural area. Although there are still improvements to be made, JMS has succeeded in achieving its aim of supplying doctors to rural areas. The recruiting system of JMS is an effective approach to overcoming the shortage of rural doctors, which has continued to be an unresolved global problem.

Education, Medical, Undergraduate↗

Pioglitazone reduces smooth muscle cell density of rat carotid arterial intima induced by balloon catheterization.

The effect of pioglitazone on balloon catheterization-induced carotid arterial intimal thickening lesion of male Wistar fatty rats and its littermates (Wistar lean rats) was investigated. Pioglitazone was administered via gastric tube at 10 mg/kg/day to 12-week-old rats for 7 days. Age-matched rats without pioglitazone were used as respective controls. Each rat was catheterized using a balloon catheter inserted from the left femoral artery to the left common carotid artery, and the endothelium in the left common carotid artery was denuded. Rats were then treated with pioglitazone for 14 days post catheterization and the left common carotid artery was removed and stained with Elastica-Masson and anti-alpha-smooth muscle actin antibody. In addition, for smooth muscle cell (SMC) culture, pioglitazone was administered at 10 mg/kg/day for 28 days to a separate group of 12-week-old rats, and the aortic medial outgrowth rate of their SMCs was measured. Age-matched rats without pioglitazone were prepared as respective controls. In comparison with the area ratio of the thickened intima/media of fatty rats without treatment, those of fatty rats with treatment and lean rats without treatment were significantly decreased by approximately 60%, and also that of lean rats with treatment to 27%. With anti-alpha-smooth muscle actin antibody staining, almost all cells present in intimal thickening were positive. Treatment with pioglitazone reduced the amount of anti-alpha-smooth muscle actin antibody-staining cells. In addition, the outgrowth rate of SMCs at day 10 compared to that in fatty rats without treatment decreased to 42% in fatty rats with treatment, 29% in lean rats without treatment and 23% in lean rats with treatment, respectively. Therefore, pioglitazone has an inhibitory effect on the growth of SMCs, and consequently suppressed carotid intimal thickening. Furthermore, this inhibitory effect was enhanced in diabetes.

Actins↗

Trial of rural practice evaluation: mutual rotation by family physicians.

OBJECTIVES: We aimed to investigate the usefulness of mutual rotation by family physicians in providing an evaluation of rural medical practices. METHODS: Between June and October 1994, each of four family physicians rotated to the practices of the other three, where they worked as a transient locum for 4-5 days and evaluated each practice. They were field faculty physicians of the Department of Community and Family Medicine, Jichi Medical School, and based at general practices accredited for undergraduate and postgraduate training. Two school-based faculty physicians also participated in the study as spare members. RESULTS: The rotation was conducted four times to complete the mutual rotation programme. There was some difference in evaluation among the practices, which indicated the characteristics of the practices. The evaluation accorded relatively well among the participants. CONCLUSIONS: Mutual rotation by family physicians provides an objective and practicable evaluation of general practices and contribute to upholding their quality, which is crucial to medical education.

Faculty, Medical↗

Structure and function of the recombinant fifth domain of human beta 2-glycoprotein I: effects of specific cleavage between Lys77 and Thr78.

In order to elucidate the mechanism of binding of beta 2-glycoprotein I (beta 2-GPI) to cardiolipin (CL), we constructed a high-level expression system for the C-terminal domain (Domain V) of beta 2-GPI using Pichia pastoris and studied its conformation and liposome-binding activity. Purified Domain V was found to have the native disulfide bonds. It had a compactly folded conformation, judging from the circular dichroism spectrum, and exhibited a cooperative unfolding transition induced by pH or urea. Also, it bound liposomes containing CL. Commercially available human beta 2-GPI is known to be selectively cleaved between Lys 317 and Thr 318. We found that bovine factor Xa weakly but specifically cleaves the corresponding site of recombinant Domain V, i.e., the peptide bond between Lys 77 and Thr 78. The conformation of the "nicked" Domain V, which was cleaved at this site, was examined by circular dichroism and fluorescence measurements, and concluded to be similar to that of the intact protein. The stability of the nicked Domain V to urea was slightly lower than that of the intact protein. Although both Domains V bound to liposomes containing CL, the affinity of the nicked Domain V was greatly reduced in comparison with the intact protein, indicating that the cleavage of the peptide bond between Lys 77 and Thr 78 controls the binding to CL. In addition, analysis of the fluorescence spectra in the presence and absence of CL liposomes indicated that Trp 76 is involved in the binding site. These results suggest that the region including Trp 76, Lys 77, and Thr 78 has a critical role in binding to CL.

Amino Acid Sequence↗

Ki-67, p53, and Bcl-2 expression of serrated adenomas of the colon.

To investigate epithelial cell proliferation and oncoprotein expression of the serrated adenoma, a term that has been used synonymously with mixed hyperplastic and adenomatous polyp, immunohistochemical staining using polyclonal antibodies against Ki-67 and p53, and a Bcl-2 monoclonal antibody, was performed and the results compared with those in hyperplastic polyps and tubular adenomas. A total of 20 serrated adenomas all characterized by a serrated glandular pattern, contained immature goblet cells, upper crypt zone mitotic figures, and a few nucleoli within the epithelial cells. Twenty hyperplastic polyps and 20 tubular adenomas (all with low-grade dysplasia) were examined, and lesions that contained separate areas of hyperplastic and adenomatous glands were excluded. The Ki-67-positive rate in the middle zone of the crypts in serrated adenomas was significantly higher than in hyperplastic polyps but lower than in tubular adenomas; a similar tendency was also noted for the upper zone. Both serrated adenomas and hyperplastic polyps demonstrated Bcl-2-positive reactivity that was essentially limited to the lower crypt zone, while in contrast, involvement in tubular adenomas often extended to the middle zone. No p53 overexpression was found in any category. These results suggest that serrated adenomas may be committed to independent growth.

Adenoma↗

Solid and cystic tumor (SCT) of the pancreas in an adult man.

Solid and cystic tumor (SCT) of the pancreas predominantly occurs in women, and the occurrence in men is extremely rare. We experienced a male case of SCT. A 38-year-old man was admitted with the complaint of upper abdominal pain. CT scan showed the presence of a mass in the head of the pancreas. The mass was composed of high density areas and low density areas. Ultrasonograms revealed the mass being composed of high echoic areas and low echoic areas. The mass was hypovascular on angiography. SCT was suspected and pancreaticoduodenectomy was performed. The cut surface of the tumor showed mainly cystic degenerative areas containing dark red hemorrhagic materials. Microscopically, there were solid areas in the periphery and pseudopapillary areas in the center. No metastasis was found in the removed lymph nodes. The tumor cells were not stained by Grimelius' silver stain. The tumor cells were positive for alpha-1-antitrypsin (AAT) and neuron-specific enolase (NSE). Pancreatic hormones such as insulin, glucagon, and somatostatin were all negative. Electron micrograph showed that tumor cells were rich in mitochondria. Zymogen granules and neurosecretory granules were not detected. Estrogen receptor (ER) and progesterone receptor (PR) were both negative.

Adult↗

Slight but significant improvement of insulin resistance of Wistar fatty rats by treatment with a disaccharidase inhibitor, AO-128.

To know whether the insulin resistance is improved by delaying carbohydrate absorption from the small intestine, we studied the effect of a disaccharidase inhibitor, AO-128, on insulin resistance of Wistar fatty rats. Rats were kept on standard laboratory chow with and without 10 ppm of AO-128 for 4 weeks, and then subjected to the glucose clamp. At the end of the 4-week treatment, plasma glucose level at 14:00 to 16:00 of AO-128 treated rats was 121 +/- 14 mg/100 ml (mean +/- S.D.), significantly lower than 226 +/- 72 mg/100 ml of the rats without AO-128. During clamp steady state under 20 mU.kg (-1).min (-1) continuous insulin infusion, glucose uptake of AO-128 treated rats was only 7.62 +/- 0.70 mg.kg (-1). min (-1), not different from 6.64 +/- 0.91 mg.kg (-1).min (-1) of rats without AO-128, but much lower than the lean littermates (20.81 +/- 3.11 mg.kg (-1).min (-1)). However, the percent suppression of hepatic glucose output was 55.2 +/- 23.8%, which, though incomplete, was significantly higher than 17.4 +/- 11.2% of rats without AO-128. The present study suggested that there were at least two, components of insulin resistance, a genetically determined and a poor-glycemic control-related, and that the latter insulin resistance was ameliorated by AO-128.

Animals↗

Acute mercury poisoning by intentional ingestion of mercuric chloride.

A 26-year-old woman ingested 0.9 g of mercuric chloride in a suicide attempt and developed hematemesis, melena and acute renal failure. Anuria persisted for 14 days. She was treated by plasma exchange, hemodialysis and peritoneal dialysis in combination with continued dimercaprol chelation. While hemodialysis was ineffective in removing the mercury, plasma exchange effectively eliminated mercury. After two plasma exchange therapies, mercury concentration in the blood decreased linearly on a log scale with half-lives of 23.1 days for whole blood and 19.1 days for plasma, using first-order kinetics. One month after ingestion, renal function recovered to normal as judged by serum creatine and blood urea nitrogen levels, although the beta 2-microglobulin level in urine was still elevated. At a follow-up examination four months later, renal function was found to be completely normal. This indicates that the renal damage caused by acute mercuric chloride poisoning may not be permanent.

Adult↗

Serum insulin and lipoprotein(a) concentrations. The Jichi Medical School Cohort Study.

OBJECTIVE: To examine the relationship between serum insulin and lipoprotein (a) [Lp(a)] concentrations in both sexes in a large population. RESEARCH DESIGN AND METHODS: The authors conducted a cross-sectional investigation of fasting serum concentrations of insulin and Lp(a), other blood tests, blood pressures, anthropological measurements, physical activity index, smoking habit, alcohol consumption, and menopause. The subjects were 1,121 men and 1,480 women, ranging between 30 and 90 years of age, who were voluntary participants in the Jichi Medical Cohort Study and who resided in one of five rural communities in Japan. RESULTS: In men, insulin, age, BMI, LDL cholesterol, triglycerides, glucose, and fibrinogen were significantly correlated with Lp(a). In women, insulin, age, LDL cholesterol, fibrinogen, and activated coagulation factor VII were significantly correlated with Lp(a). However, all correlations were weak in either sex. Insulin was inversely correlated with Lp(a) in both sexes. However, the coefficients were weak (r = -0.16 in mean and r = -0.06 in women). In the partial correlation analyses, Lp(a) was not significantly associated with insulin in either sex. The result was not influenced by selecting the subjects on the basis of detectable values of insulin and Lp(a) and stratifying them by serum glucose level. CONCLUSIONS: There was no significant relationship found between serum insulin and Lp(a) concentrations in either sex of the cohort, which indicates that Lp(a) does not play a role in the increased risk of cardiovascular disease in hyperinsulinemic subjects.

Adult↗

Resormycin, a novel herbicidal and antifungal antibiotic produced by a strain of Streptomyces platensis. I. Taxonomy, production, isolation and biological properties.

Resormycin, a novel herbicidal and antifungal antibiotic, was isolated from the cultured broth of streptomycete strain. The strain was isolated from a soil collected at Yokohama-shi, Kanagawa Prefecture, Japan, and identified as Streptomyces platensis MJ953-SF5. Resormycin was purified by active charcol, Amberlite IRC-50, Amberlite CG-50 and Sephadex LH-20 column chromatographies. Resormycin markedly inhibited the growth of monocotyledonous and dicotyledonous weed. The antibiotic showed antimicrobial activity against phytopathogenic fungi.

Antifungal Agents↗

Resormycin, a novel herbicidal and antifungal antibiotic produced by a strain of Streptomyces platensis. II. Structure elucidation of resormycin.

A novel herbicidal antibiotic, resormycin, was isolated from the culture broth of Streptomyces platensis MJ953-SF5. The structure of resormycin is determined to be (2Z)-2-N-[2N-[(3S)-3,6-diaminoheptanoyl]-(2S)-3-hydroxyva lyl]amino-3- (4-chloro-3,5-dihydroxy)phenylpropenoic acid by spectroscopic analyses, degradation studies and X-ray crystallography.

Antifungal Agents↗

Formamicin, a novel antifungal antibiotic produced by a strain of Saccharothrix sp. I. Taxonomy, production, isolation and biological properties.

Formamicin, an antifungal antibiotic, was isolated from the cultured broth of an actinomycete strain. The strain was isolated from a soil collected at Setagaya-ku, Tokyo, Japan, and identified as Saccharothrix sp. MK27-91F2. Formamicin was extracted with acetone from cultured mycelia and purified by silicagel and Sephadex LH-20 column chromatographies and CPC (Centrifugal liquid-liquid Partition Chromatography). Formamicin showed strong antimicrobial activity against phytopathogenic fungi.

Actinomycetales↗