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Biomedical subjects

H Ikeda

Publications and source records attributed to H Ikeda.

At least 631 records · Page 35Linked to original sources

Expression of endogenous retroviruses, ERV3 and lambda 4-1, in synovial tissues from patients with rheumatoid arthritis.

We addressed the question of whether or not expression of human endogenous retroviruses (ERV), ERV3 and lambda 4-1, is related to the pathogenesis of rheumatoid arthritis (RA). In genomic Southern hybridization, there were no significant differences between RA patients and healthy volunteers with regard to frequencies of restriction fragment length polymorphism (RFLP) patterns, for either ERV3 or lambda 4-1. By Northern blot analysis using fresh synovial tissues, cultured synovial cells, and peripheral blood mononuclear cells (PBMC) from patients with RA, we noted two molecular species of ERV3 mRNAs of 3.5 kb and 9.0 kb sizes, and one single molecular species of lambda 4-1 mRNAs of 4.2 kb size. The expression was detected not only in RA patients but also in synovial cells from osteoarthritis (OA) as a non-RA control and PBMC from healthy volunteers, and was not related to RA activities or treatments. Although ERV3 and lambda 4-1 expression may not be directly associated with the pathogenic pathway of RA, the possibility exists that human ERV may have a causative role in autoimmune diseases, including RA. We also examined the effect of cytokines on the transcriptional regulation of ERV3. Although the level of ERV3 expression in cultured synovial cells did not change with IL-1 beta treatment, the level for cultured proximal tubular epithelial cells (hKEC) was up-regulated.

Arthritis, Rheumatoid↗

Cushing's disease due to female gonadotroph adenoma of the pituitary.

A 39-year-old woman presented with amenorrhoea, hyperprolactinaemia and sellar mass. Bromocriptine normalized PRL levels but failed to suppress tumour growth. Subsequently, she developed clinical signs and elevated blood cortisol levels consistent with a diagnosis of Cushing's disease. A pituitary tumour was removed which was immunoreactive for ACTH. Electron microscopic examination, however, revealed a female gonadotroph adenoma indicating that adenoma cells regarded as gonadotrophs by ultrastructural analysis may occasionally secrete ACTH and cause Cushing's disease.

Adenoma↗

Gastrointestinal manometry findings in a case with dilated small bowel and disturbed transit treated successfully with bowel plication.

We report the manometric findings in a case of dilated small bowel and disturbed transit successfully treated with plication of the dilated small bowel. The female newborn infant required total parenteral nutrition following an operation for small bowel atresia. X-ray showed a dilated proximal small bowel. Jejunal manometry showed normal phase 3 migration but persistently low-amplitude contractions in the dilated segment. After plication of the dilated intestine, symptoms of bowel obstruction disappeared. A second manometry two weeks after the operation showed contractions with normal amplitude. These findings indicate that: (1) disturbed transit in the dilated intestine proximal to small intestinal atresia is associated with persistently low contraction amplitude, and (2) the amplitude can be increased by the plication of the dilated loop.

Digestive System↗

Treatment of a stage I testicular yolk sac tumor with vascular invasion.

There is controversy concerning the treatment of stage I yolk sac tumor of the testis, particularly of those with histological factors that indicate a high risk of relapse. Usually orchiectomy alone is sufficient and adjuvant chemotherapy is unnecessary. Retroperitoneal lymphadenectomy is indicated for patients with persistently high alpha-fetoprotein. Once recurred, treatment at that time is thought to be curative. However, postoperative chemotherapy may be necessary for patients with a tumor expressing histological factors that predict possible relapse. In this paper we report on a case of a 2 year old boy whose tumor invaded the testicular veins. The patient suffered from recurrent disease but was successfully treated by chemotherapeutic regimens including cisplatin and retroperitoneal lymphadenectomy. The importance of the histological factors in making a decision on the treatment strategy for stage I testicular yolk sac tumor is discussed.

Antineoplastic Combined Chemotherapy Protocols↗

Visual disturbances in patients with pituitary adenoma.

INTRODUCTION: To clarify the relationship between visual disturbances caused by pituitary adenomas and the degree of chiasmal compression, MRI (1.5T) findings were assessed two dimensionally. MATERIAL AND METHODS: 50 cases of pituitary adenomas and 17 control cases were studied. The position of the optic chiasm was measured by the distance from the line of the frontal base and posterior clinoid process on the sagittal T1 weighted image, and from the upper surface of the bilateral internal carotid artery on the coronal T1 image. RESULT: Visual disturbances appeared when the chiasm was displaced to more than 8 mm above the aforesaid reference level on the sagittal image and more than 13 mm above on the coronal image. There was a good correlation between the appearance of visual field defects and the degree of chiasmal compression. CONCLUSION: The degree of chiasmal displacement measured by MRI two dimensionally can provide useful information for predicting the appearance of visual disturbances.

Adenoma↗

Soluble interleukin-6 receptors in inflammatory bowel disease: relation to circulating interleukin-6.

The in vivo appearance of soluble interleukin (IL)-6 receptor (sIL-6R) in serum from patients with inflammatory bowel disease was examined using an enzyme linked immunosorbent assay (ELISA). The serum sIL-6R concentrations in patients with active disease (ulcerative colitis, 148.4 (5.1); Crohn's disease, 142.3 (9.3) ng/ml; mean (SEM)) were significantly raised compared with those in patients with inactive disease (ulcerative colitis, 116.2 (7.2); Crohn's disease, 114.3 (7.1) ng/ml), some other type of colitis (104.8 (11.6) ng/ml), or in normal subjects (107.3 (2.4) ng/ml). These differences were also seen in paired samples examined during both active and inactive phases. Additionally, serum sIL-6R and IL-6 concentrations correlated significantly with C-reactive protein levels in both ulcerative colitis and Crohn's disease patients (r = 0.23 and 0.56, respectively; p < 0.05 for both). Furthermore, gel filtration analysis of serum from these patients showed two major peaks of immunoreactive IL-6-one peak corresponding to free IL-6 and another peak to sIL-6R-bound IL-6-this was further confirmed by a luminescence sandwich ELISA. These results, together with its in vitro effects, indicate that natural sIL-6R may function as a powerful enhancer of the IL-6-dependent immune processes observed in inflammatory bowel disease.

Adolescent↗

Long-term ingestion of lactosucrose increases Bifidobacterium sp. in human fecal flora.

We investigated the influence of lactosucrose on the intestinal flora of healthy volunteers. Eight healthy volunteers (male:female = 4:4, age 34 +/- 4 years) received 6 g of lactosucrose daily for 8 weeks. Fecal microflora, bacterial metabolites, pH, and moisture were analyzed before and after the administration of lactosucrose. The results showed that the number and percentage of Bifidobacterium sp. in relation to the total bacteria significantly increased during the period of lactosucrose administration. Although fecal putrefactive products, fatty acids, pH, moisture content, and stool volume did not show significant changes during the test period, the amount of fecal phenol showed a negative correlation with the number of Bifidobacterium sp. Fecal ammonia significantly decreased after 4 and 8 weeks of lactosucrose administration, and 1 week after the end of lactosucrose administration, compared with results after a 1-week administration of lactosucrose. When the administration was stopped, the percentage of Bifidobacterium sp. in relation to the total count gradually decreased to the same level as before the administration of lactosucrose. These results suggest that under physiological conditions, lactosucrose acts on the intestinal microflora as a growth factor of Bifidobacterium sp.

Administration, Oral↗

Studies on antidiabetic agents. XII. Synthesis and activity of the metabolites of (+/-)-5(-)[p(-)[2-(5-ethyl-2-pyridyl)ethoxy]benzyl]-2,4- thiazolidinedione (pioglitazone).

The metabolites of (+/-)-5(-)[p(-)[2-(5-ethyl-2- pyridyl)ethoxy]benzyl]-2,4-thiazolidinedione (1, pioglitazone), which is a representative insulin-sensitizing agent, were synthesized to confirm their structures and for studies of their pharmacological properties. Of the metabolites identified, a compound hydroxylated at the 2-position of the ethoxy chain (3) and compounds oxygenated at the ethyl side chain attached to the pyridine ring (4, 5) were found to be active, although the potency was slightly lower than that of the parent compound.

Animals↗

Synthesis of 3-ureido derivatives of coumarin and 2-quinolone as potent acyl-CoA: cholesterol acyltransferase inhibitors.

Novel 3-ureido derivatives of 4-phenylcoumarin and 4-phenyl-2-quinolone were synthesized and evaluated for acyl-CoA: cholesterol acyltransferase (ACAT)-inhibitory activity. These derivatives inhibited rat intestinal ACAT with IC50 values at the 10(-8) to 10(-9) M level and were found to normalize plasma cholesterol levels in cholesterol-fed rats when administered as dietary admixtures.

Animals↗

Genetic variation and geographic distribution on the mitochondrial DNA in local populations of the musk shrew, Suncus murinus.

The musk shrew (Suncus Murinus) is widely distributed throughout Asia and East Africa. The mitochondrial DNA (mtDNA) of this species was analyzed in individuals from 31 local populations in nine Asian countries and Mauritius, using 17 restriction endonucleases. Although fourteen and nine mtDNA haplotypes were detected from Bangladesh and Nepal, respectively, one to four haplotypes were found in each Southeast Asian country, and one common haplotype existed in Japan, Philippines, Vietnam, Thailand and Indonesia. Clustering analysis of mtDNA haplotypes classified shrew populations to three groups--continental group (Bangladesh and Nepal), islands' group (insular countries and Vietnam) and Malay group. The average nucleotide diversity among these three groups was calculated to be about 3.5%. These results indicate that the origin of feral populations in this species might be old and their population sizes are extremely large in the continent, and suggest a rapid spread of this animal throughout the islands. Although we have not shown yet an evidence of close relationships between islands' and continental mtDNA haplotypes, it is likely that the musk shrew had migrated from the continent in South Asia to the islands in Southeast Asia recently.

Animals↗

3,4-dihydroxyphenylalanine (DOPA) decarboxylase deficiency and resultant high levels of plasma DOPA and dopamine in unfavorable neuroblastoma.

Neuroblastoma (NB) is a tumor which arises from neural crest cells. In the developing neural crest cells, the induction of 3,4-dihydroxyphenylalanine (DOPA) decarboxylase is more delayed than that of tyrosine hydroxylase and dopamine-beta-hydroxylase. If NB cells are arrested in an early stage of neural crest development, the induction of DOPA decarboxylase is insufficient and the accumulation and secretion of DOPA can be caused. The biochemically immature phenotype is thought to represent the undifferentiated characteristics of the cells and might correlate with the grade of malignancy. To investigate whether the hypothesis is clinically applicable or not, we have measured plasma DOPA, dopamine and urinary catecholamine metabolites in NB patients. The levels of plasma DOPA, dopamine, urinary homovanillic acid (HVA) and vanillactic acid (VLA) were significantly higher in patients with unfavorable NBs and the higher plasma DOPA level was significantly associated with the patients' age (> 1 year old), tumor stage (III, IV) and DNA diploidy. Serial determination of plasma DOPA was a good monitor of the disease course. These results are compatible with the hypothesis on DOPA decarboxylase deficiency and DOPA secretion in undifferentiated, unfavorable NBs. In conclusion, the plasma DOPA can be used to predict patients' prognosis as well as to follow up patients with NB.

Biomarkers, Tumor↗

Magnetic resonance angiography of cerebral arteriovenous malformations.

Magnetic resonance (MR) angiography as a method for the long-term follow-up of cerebral arteriovenous malformations (AVMs) was assessed in 14 patients with cerebral AVMs. These patients were either untreated or treated with transarterial embolization and/or stereotactic radiosurgery (gamma knife). Two-dimensional- and three-dimensional (3D)-time-of-flight (TOF) techniques were useful for following AVMs with a small nidus and few feeders and drainers which were either untreated or had been treated only a few months previously. 3D-TOF MR angiography with a contrast agent was more useful for visualizing the vascular structure, including the residual nidus, during long-term follow-up of treated AVMs.

Adult↗

Production of the new antibiotic tetrahydrokalafungin by transformants of the kalafungin producer Streptomyces tanashiensis.

The new antibiotic tetrahydrokalafungin was produced by the transformants of kalafungin producing S. tanashiensis and kalafungin-nonproducing mutants carrying the recombinant plasmid pKU523. This plasmid consists of pKU501 (J. Antibiotics 44: 995 approximately 1005, 1991) which contains the gene cluster for kalafungin biosynthesis, and additional 5 kb stability region of SCP2*.

Anti-Bacterial Agents↗

Production of 6,8a-seco-6,8a-deoxy derivatives of avermectins by a mutant strain of Streptomyces avermitilis.

Streptomyces avermitilis produces the anthelmintic and insecticidal secondary metabolite avermectins. Following mutagenesis of a recombinant strain, S. avermitilis K2038 (aveD X) with N-methyl-N'-nitro-N-nitrosoguanidine, a derivative strain K2057 (aveD aveE X), was isolated, which produced seven avermectin-related compounds different from the eight components of avermectins. Four among these seven compounds from mutant K2057 were found to be new metabolites. Their structures were 4'-deoleandrosyl-6,8a-seco-6,8a-deoxyavermectin B1a, 4'-deoleandrosyl-6,8a-seco-6,8a-deoxy-5-oxoavermectin B1a, 4'-deoleandrosyl-6,8a-seco-6,8a-deoxy-5-oxoavermectin B2a and 6,8a-seco-6,8a-deoxy-2,5-didehydroavermectin B2a, all of which lack the furan ring at C-6, C-8a. The mutation affecting the formation of the furan ring (aveE) is located in the center of the gene cluster for avermectin biosynthesis.

Anthelmintics↗

Isochromophilones I and II, novel inhibitors against gp120-CD4 binding produced by Penicillium multicolor FO-2338. I. Screening, taxonomy, fermentation, isolation and biological activity.

Isochromophilones I and II, the first novel gp120-CD4 binding inhibitors of microbial origin, were isolated from a cultured broth of a soil fungus designated as Penicillium multicolor FO-2338. These compounds were obtained as yellow powders from the cultured broth together with the known related compounds sclerotiorin, ochrephilone and rubrorotiorin. Isochromophilones I and II (C23H25O5Cl and C22H27O4Cl, respectively) have an azaphilone skeleton and a chlorine atom. Isochromophilones strongly inhibited gp120-CD4 binding (IC50: 6.6 and 3.9 microM, respectively), but the other related compounds did not. Isochromophilone II inhibited significantly HIV replication in peripheral human lymphocytes at 25 microM.

Antiviral Agents↗