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Biomedical subjects

H Nawata

Publications and source records attributed to H Nawata.

At least 217 records · Page 12Linked to original sources
PubMed1997

Transcatheter neodymium-yttrium-aluminum-garnet laser coagulation of canine ventricle using a balloon-tipped cardioscope.

The feasibility of transcatheter laser ablation of the canine left ventricle (LV) was tested using a newly developed cardioscope. In 17 anesthetized dogs, a combined laser-endoscope catheter, consisting of an endoscope encased in a 7-French flexible catheter with an inflatable and transparent balloon at the distal end, was introduced into the LV via the carotid artery. A 1064-nm neodymium-yttrium-aluminum-garnet (Nd:YAG) laser was delivered by laser optic fiber, which was introduced through the transport channel and positioned inside the saline-filled balloon. In 16 of 17 dogs, the endocardial surface of the LV was clearly observed. Laser energy totaling 500-5,000 J was applied sequentially in 13 dogs and laser irradiation was completed in all but 2 of the dogs. The excised hearts revealed well-demarcated oval-shaped lesions 2.5-9.5 mm deep in 7 of 11 dogs. Histologic sections revealed coagulation necrosis surrounded by a rim of contraction band necrosis. Thus, transballoon laser photocoagulation of the beating LV is feasible. The newly combined laser-endoscope catheter, which is still in its preliminary stages and needs to be improved to increase the success rate of photocoagulation, appears to be a promising alternative modality for catheter ablative therapy for ventricular tachycardia.

Animals↗
PubMed1997

Relationship between histological type and endosonographic detection of regional lymph node metastases in gastric cancer.

The aim of the study was to compare the ability of endoscopic ultrasonography (EUS) in detecting lymph node metastases in differentiated and undifferentiated gastric adenocarcinoma. EUS was performed in 149 patients with differentiated or undifferentiated gastric cancer. Histopathological findings were compared with pre-operative EUS findings in a total of 2961 resected lymph nodes. The EUS detection rates of metastasis to individual nodes in relation to node size, the ratio of the metastasized area to the cross-sectional area of the node and to the depth of primary tumour invasion, were also investigated. The accuracy and negative predictive values of EUS for detecting metastatic lymphadenopathy in each patient were significantly higher for differentiated (87%, 94%) than for undifferentiated (71%, 71%) tumours. The detection rate of individual node metastasis was higher for differentiated (31%) than for undifferentiated (21%) tumours. For differentiated lesions, EUS detected more small nodal metastases (< 5 mm in diameter) (p < 0.01) and more nodes involved with a relatively small proportion of the metastasized area to the cross-sectional area of the node (< 1/3 involvement) (p < 0.05). In relatively superficial lesions, such as pT1 and pT2, the pre-operative EUS detection rate of metastatic nodes was higher for differentiated than for undifferentiated tumours. In conclusion, the ability of EUS to detect nodal metastases is related to the histological type of gastric cancer.

Adenocarcinoma↗
PubMed1997

Pre-operative TN staging of gastric cancer using a 15 MHz ultrasound miniprobe.

The aim of the study was to evaluate the usefulness of and problems associated with a new endoscopically guided ultrasound miniprobe, used for pre-operative staging of gastric cancers. 59 cases of gastric cancer were prospectively examined with a 15 MHz ultrasound miniprobe. The results of the ultrasound imaging were compared with the histological findings of the resected specimens. The accuracy of the miniprobe for depth of invasion (T category) was 61% for all tumours, and 72% and 40%, respectively, for T1 and T2 to T4 lesions. If indeterminate cases due to ultrasound attenuation were excluded, the accuracy was improved to 82% for T1 and 57% for T2 to T4 tumours, respectively. The accuracy of the miniprobe for nodal staging (N category) was 69% overall, and 86%, 25% and 14% for stages N0, N1 and N2, respectively. In tumours classified on the basis of endoscopic types, the miniprobe staged early type gastric cancers (T category = 73%, N category = 80%) significantly (p < 0.01) more accurately than advanced ones (T category = 21%, N category = 36%). This study suggests that the miniprobe is indicated for pre-operative TN staging when endoscopy reveals an early gastric cancer.

Adenocarcinoma↗
PubMed1997

Cloning and characterization of the 4.2 kb region of the rat thyrotropin receptor promoter.

We previously identified an approximately 200 bp "minimal promoter" of the rat TSH receptor (TSHR) gene which is essential for the promoter activity. In the present study, we have cloned and characterized an upstream region of the TSHR promoter to disclose additional functional element(s). We screened a rat genomic library and obtained a DNA fragment which contained a 4.2 kb 5'-flanking region. This fragment was 2.5 kb longer than that we previously studied (1.7 kb). To assess the promoter activity, chimeric plasmids containing the 4.2 kb promoter and its 5'-deletions ligated to a chloramphenicol acetyltransferase gene were transfected into thyroid and non-thyroid cells. These plasmids expressed significant promoter activity in FRTL-5 and FRT thyroid cells, but not in BRL liver cells. The strongest promoter activity was expressed by the -199 bp promoter, and the longer promoter expressed rather decreased activity. Co-expression of thyroid transcription factor-1 (TTF-1) increased the activity of the promoter region from -3187 to -199 bp, which encompassed one or two TTF-1 binding sites we previously identified, but not the -4206 bp promoter. In addition, FRTL-5 stable transfectants each having a chimeric construct were cultured in the presence or absence of TSH. All transfectants expressed higher promoter activity in the absence of TSH than in the presence of TSH, in particular, the -3187 bp plasmid expressed significantly higher activity by comparison to the -2617 and -4206 bp constructs. This result indicates that the region between -3187 and -2617 bp may contribute to TSH/cAMP-induced suppression and also suggests that the region between -4206 and -3187 bp involves the element(s) for constitutive suppression of the promoter activity. These results not only suggest that the 4.2 kb upstream region of the TSHR gene possibly contains some elements for the regulation of the gene expression, but also emphasize the importance of the minimal promoter region which we previously identified for the efficient expression of the gene.

Animals↗
PubMed1997

A case of mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes associated with diabetes mellitus and hypothalamo-pituitary dysfunction.

A 45-year-old woman with mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) had muscular atrophy, severe cerebral and cerebellar atrophy, and cardiac hypertrophy. She also had diabetes mellitus treated with insulin, and sensorineural hearing loss. Ragged-red fibers were observed on muscle biopsy and an adenine to guanine transition mutation at position 3243 of her mitochondrial DNA was confirmed. Further investigations revealed that she also had hypothalamo-pituitary dysfunction. It appears that diabetes mellitus, hypothalamo-pituitary dysfunction, and the other abnormalities are all associated with mitochondrial dysfunction in this patient.

Atrophy↗
PubMed1997

Immunohistochemical study of prostacyclin-stimulating factor (PSF) in the diabetic and atherosclerotic human coronary artery.

Prostacyclin (PGI2) synthesis by vascular endothelial cells (ECs) decreases in diabetic subjects, possibly leading to the development of diabetic angiopathy, such as that seen in atherosclerosis. We recently found a novel bioactive peptide, prostacyclin-stimulating factor (PSF), which stimulates PGI2 synthesis by cultured aortic ECs. Our previous studies demonstrated that PSF is dominantly expressed by arterial smooth muscle cells (SMCs). In the present study, we found PSF to exist in the SMCs of human coronary arteries by means of immunohistochemical methods. Human coronary arteries obtained from autopsies were divided into four subgroups, with or without NIDDM and/or myocardial infarction. Immunostaining for PSF was performed by the avidin-biotin peroxidase complex method using a purified anti-PSF antibody, and the immunostaining for PSF was assessed semiquantitatively. PSF staining was markedly reduced in coronary arterial SMCs from patients with NIDDM and/or myocardial infarction. In addition, the effect of a high glucose culture on PSF mRNA expression and PSF production in bovine aortic SMCs was examined by immunocytochemical staining and both Western and Northern blot analyses. The immunostaining and immunoblot band for PSF also significantly decreased when bovine aortic SMCs were cultured with high concentrations of glucose. Furthermore, as compared with the SMCs cultured with a physiological glucose concentration, the density ratio of PSF mRNA to 28S rRNA expression significantly decreased when the SMCs were cultured with high concentrations of glucose. These results strongly suggest that the decreased PSF production may thus results in a decreased production of PGI2 in the coronary artery, thus leading to the development of both diabetic macroangiopathy and atherosclerosis.

Adult↗
PubMed1997

Biphenotypic blast crisis of chronic myelogenous leukemia: abnormalities of p53 and retinoblastoma genes.

The molecular mechanisms responsible for progression of chronic myelogenous leukemia (CML) to blast crisis have not been well defined. Blast crisis may be partially related to inactivation of tumor suppressor genes/such as p53 or retinoblastoma (Rb) gene. There is evidence for an association of blast cell phenotypes in CML with alterations of these genes: a strong association of myeloid phenotypes with abnormalities of the p53 gene and a weaker association of lymphoid phenotypes with abnormalities of the Rb system. We found a marked decrease in Rb gene product and rearrangements of the p53 gene simultaneously in two cases of biphenotypic blast crisis of CML (myeloid and B-lymphoid). These results support the association of blast cell phenotypes with alterations in tumor suppressor genes in CML blast crisis.

Blast Crisis↗
PubMed1997

[Insulin secretin and resistance accompany immobilization of the aged patient].

Physical activity is known to increase glucose tolerance and insulin sensitivity. To examine the influence of physical inactivity on insulin sensitivity in aged people, insulin sensitivity and secretion was measured by using a two-step euglycemic glucose clamp, a glucagon tolerance test (GTT), an oral glucose tolerance test (OGGT) and urinary CPR excretion in 11 aged patients immobilized in bed for more than 12 weeks. The results were compared with those of nine healthy mobile aged controls. The muscle volume of the immobilized patients decreased by 20-25% compared with that of the controls, and insulin sensitivity decreased 50% in each step. These results mean that the immobilized patients had decreased insulin sensitivity and responsiveness, even when there was muscle atrophy. The glucose and insulin responses in both the GTT and OGTT showed that there was a slight decrease in the initial response of insulin in the immobilized patients and was in the controls compared with adolescent controls. There was no difference in the initial response of insulin between the immobilized patients and the aged controls. The ratio of impaired glucose tolerance in the OGTT was 4/11 of the immobilized patients and 3/9 of the controls. Total insulin secretion was increased and insulin sensitivity and responsiveness was decreased in the immobilized patients. This suggests that the decreased insulin sensitivity was compensated for increased by insulin secretion in the immobilized patients.

Aged↗
PubMed1997

Elevated L-kynurenine level and its normalization by prednisolone in a patient with eosinophilia-myalgia syndrome.

We report a L-tryptophan-induced case of eosinophilia-myalgia syndrome in a Japanese woman and describe the time course of changes in tryptophan metabolism observed during steroid therapy. She had taken 1.0 g of the implicated L-tryptophan daily. When admitted due to painful swelling of her extremities, eosinophil count was 22.3 x 10(9)/L. Before prednisolone treatment, her serum L-kynurenine level was 10.2 mumol/L, a level about three-fold higher than the normal value, while serum tryptophan level was abnormally low (23.1 mumol/L). On the 14th day of prednisolone treatment (40 mg daily), L-kynurenine was declined to 8.1 mumol/L and, concomitantly, L-tryptophan level increased to the normal range (51.0 mumol/L). Subsequently, on the 42nd day of therapy, serum L-kynurenine was normalized. In contrast, serum serotonin level was unchanged throughout the course of this therapy. Prednisolone dramatically reduced the elevated serum L-kynurenine with a reciprocal increase in serum L-tryptophan indicates that abnormal tryptophan metabolism, may play a role in the pathogenesis of eosinophilia myalgia syndrome, and that the observed effect of steroid treatment was due to suppression of elevated activity of indoleamine 2, 3-dioxygenase, a first rate-limiting enzyme of the kynurenine pathway.

Anti-Inflammatory Agents↗
PubMed1997

Effect of beraprost sodium on the increased transendothelial permeation of albumin induced by high concentration of glucose.

To determine whether a decrease in prostacyclin production is involved in the increase in endothelial permeability induced by a high concentration of glucose, we evaluated the effect of beraprost sodium, a stable prostacyclin analog, on the transendothelial permeation of albumin in cultured aortic cells. Permeation of albumin across an endothelial cell monolayer was significantly greater when the cells were cultured with a high concentration of glucose (400 or 800 mg/dl) than when they were cultured with 100 mg/dl glucose. No significant change in the permeation of albumin was observed when cells were cultured with 100 mg/dl glucose as compared with 100 mg/dl glucose plus 700 mg/dl mannitol. The addition of beraprost sodium to the culture medium completely restored the increase in the permeation of albumin brought about by 400 mg/dl glucose. These results suggest that increased transendothelial permeation of albumin by high glucose may be due in part to a decrease in prostacyclin production by the endothelial cells. Beraprost sodium may restore the endothelial barrier function affected by a high concentration of glucose.

Albumins↗
PubMed1997

[Recent progress in the research field of nuclear receptors].

In the research field of nuclear receptors, the studies on the protein factors which interact with the steroid hormone receptors and regulate the transcriptional activity, and on the alpha and beta isoforms of glucocorticoid receptor have been in great progress. The include "intermediary Factors" such as RIP140, TIF-1, for the AF-2 which contribute to ligand-dependent transactivation function of the receptors. ARA70 which specifically interacts with androgen receptor was also cloned recently. Informations obtained from steroid hormone receptor knockout-mice experiments can also be available for the estrogen, glucocorticoid, and progesterone receptors. Furthermore, there have been more than sixty orphan receptors identified in these eight years, including HNF, Ad4BP, DAX-1, and nur77/NGFIB, some of which are mutation target genes of human congenital diseases.

Animals↗
PubMed1997

A case of Meckel's diverticulum complicated by stenosis of the colon.

Meckel's diverticulum is a common anomaly of the GI tract that is known to cause small intestinal obstruction. A 17-yr-old male who had no history of previous surgery was admitted with intermittent abdominal pain. A barium enema showed extraintestinal compression of the ascending colon, suggesting the existence of a congenital band. Laparoscopy revealed that the ascending colon was lifted up and compressed by the intestinal end of a Meckel's diverticulum with a fibrous band connecting to the umbilicus. The portion of the ileum including the Meckel's diverticulum was resected. This is the first case of stenosis of the colon caused by a Meckel's diverticulum.

Adolescent↗
PubMed1997

A case of successfully treated giardiasis in pancreas.

We report a case of giardiasis in the pancreas in a patient with diabetes mellitus. The patient is interesting in the following: 1) Giardia lamblia was found only in the pancreas and not in the gall bladder by cytology on endoscopic retrograde cholangiopancreaticography (ERCP) and by cerulein-secretin test (CST). 2) ERCP revealed multiple small cysts scattered throughout the pancreas. 3) Decreased pancreatic exocrine function was recovered by treatment with metronidazole.

Aged↗
PubMed1997

[Virilization syndrome and hirsutism].

Severe virilization syndrome is seen in testosterone-producing ovarian or adrenal tumor while symptom in late-onset congenital adrenal hyperplasia (CAH) are usually mild hirsutism and amenorrhea. We determined the serum levels of 17 alpha-hydroxy pregnenolone (17P5) and 17 alpha-hydroxyprogesterone (17P4) 60 min after the intravenous injection of 250 micrograms of ACTH in 10 normal Japanese females with age ranging from 18 to 29 years old. In this test, 1 mg of dexamethasone had been administered orally at 11 p.m. on the previous day to suppress the effect of endogenous ACTH. The ratio of 17P5 to 17P4 was 10.0 +/- 3.6 (mean +/- SD). Five females with hirsutism of no ovarian origin showed normal responses to this rapid ACTH test, suggesting that the incidence of the late-onset CAH is not so high as reported previously.

Adolescent↗
PubMed1996

Thermolabile beta-2 macroglycoprotein (Hakata antigen) in liver disease: biochemical and immunohistochemical study.

Thermolabile beta-2 macroglycoprotein is a novel serum protein that was detected by an autoantibody in sera of a Japanese woman with systemic lupus erythematosus. We developed an enzyme-linked immunosorbent assay for this glycoprotein and measured its serum levels in patients with chronic liver disease. There were significant correlations between serum levels of this glycoprotein and those of albumin and cholinesterase. The serum levels of TL beta 2MG decreased with increasing severity of cirrhosis. Immunohistochemical staining using monoclonal anti-thermolabile beta-2 macroglycoprotein antibody revealed positive staining in the cytoplasm of the hepatocytes. These data strongly suggested that hepatocyte may be one of the production sites of this glycoprotein. Measurement of serum levels of this glycoprotein was useful for evaluation of hepatic function in chronic liver disease.

Adult↗
PubMed1996

Dehydroepiandrosterone markedly inhibits the accumulation of cholesteryl ester in mouse macrophage J774-1 cells.

To clarify the antiatherogenic mechanism of action of dehydroepiandrosterone (DHEA), we investigated the effects of DHEA on the accumulation of cholesteryl ester (CE) in cultured mouse macrophage J774-1 cells. The accumulation of CE in J774-1 cells in the presence of acetyl low density lipoprotein (AcLDL) and 10(-5) mol/l DHEA was significantly reduced to 30% of the control values for 24 h. The marked effect of DHEA was observed as early as 6 h and continued at least for 48 h. This reduction by DHEA was dose-dependent and occurred starting at a DHEA dose of 5 x 10(-7) mol/1 for 24 h. DHEA treatment did not induced any changes in the cell surface binding, cell-association, or degradation of AcLDL. In comparison, the DHEA analogues, 8354 and 8356, which are known to be much stronger inhibitors of glucose 6-phosphate dehydrogenase than DHEA, did not show as marked an effect as DHEA on the accumulation of CE during the first 6 h. However, after 24-48 h of incubation, both 8354 and 8356 caused a marked reduction in the accumulation of CE similar to that observed with DHEA. A quantitative analysis of the cellular cholesterol content revealed that DHEA caused a marked reduction in CE with a concomitant continuous increase in free cholesterol (FC), while the DHEA analogues caused a marked reduction in CE with no change in FC. DHEA demonstrated little inhibitory effect on 25-hydroxycholesterol-driven esterification. Moreover, 10(-5) mol/1 DHEA induced a CE reduction in the foam cells induced by AcLDL. The CE-reducing capacity was also observed in the DHEA analogues. This CE-reducing capacity disappeared, however, when acyl CoA:cholesterol acyltransferase inhibitor, 58-035, was also present. Based on these findings, it can be concluded that the inhibitory effect of DHEA on the CE storage in response to AcLDL can be explained, at least in part, by two mechanisms. First, a recently published mechanism, namely, the inhibitory action of DHEA on lysosomal cholesterol transport, correlates well with the inhibition against foam cell transformation by DHEA in the early phase (at 6 h) observed in our study. With regard to the second mechanism, the CE-reducing capacity of DHEA from CE-laden foam cells, which appears to be related to a decreased cholesteryl ester cycle, may contribute to the inhibitory effect on the CE storage in the late phase (at 24 h and 48 h). These phase-specific inhibitory mechanisms of DHEA on the CE-storage may therefore partly explain the antiatherogenic action of DHEA.

Androstenes↗
PubMed1996

Structural characterization of human Ad4bp (SF-1) gene.

Ad4BP (or steroidogenic factor 1, SF-1) has been implicated to be an essential transcriptional factor for steroidogenesis as well as for the development of the reproductive axis. We elucidated the structure of the human Ad4BP gene. The gene is about 30 kb long and is split into 7 exons including a non-coding exon 1. The deduced amino acid sequence of the human Ad4BP consists of 461 amino acid residues and was highly homologous to those of other mammalian species.

Amino Acid Sequence↗