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Biomedical subjects

Y Imamura

Publications and source records attributed to Y Imamura.

537 records · Page 30Linked to original sources

Effect of antiserum to monoclonal anti-islet cell surface antibody on pancreatic insulitis in non-obese diabetic mice.

Immunotherapeutic intervention has been studied in non-obese diabetic (NOD) mice. Twenty-five male NOD mice aged 6 weeks were treated with anti-mouse T lymphocyte serum (ATS), N-(2-carboxyphenyl)-4-chloroanthranilic acid disodium salt (CCA); a non-specific immunostimulant which seems to potentiate the suppressor T cell activity, and antiserum raised against previously reported monoclonal antibody 3A4 to the surface of islet cells. Pancreatic islets from NOD mice sacrificed at 12 weeks of age were scored morphologically for the severity and the frequency of insulitis. Both the severity of insulitis in each islet and the frequency of insulitis-positive islets in each pancreas were reduced in the groups treated with ATS (group B), antiserum to 3A4 (group D) and a combination of antiserum plus CCA (group E) in comparison with other groups (control: group A and CCA: group C). At 8 weeks of age, the binding capacities of sera to insulinoma cells measured by protein A radioligand assay were significantly decreased in the groups treated with antiserum to 3A4 (groups D and E) as compared with those in the other groups. These results suggest that both ATS and antiserum to 3A4 prevent the occurrence and the progress of insulitis in NOD mice, but the immunosuppressive mechanisms differ from each other; therefore, combination therapy with these suppressants may be more effective in the prevention of Type 1 diabetes mellitus.

Animals↗

Measurement of activities in two different angiotensin II generating systems, chymase and angiotensin-converting enzyme, in the vitreous fluid of vitreoretinal diseases: a possible involvement of chymase in the pathogenesis of macular hole patients.

PURPOSE: To investigate possible involvement of chymase and angiotensin-converting enzyme (ACE) in the pathogenesis of vitreoretinal diseases, both of which are related to the production of angiotensin II. METHODS: We measured chymase and ACE activities in the vitreous in the 54 affected eyes of 54 patients who had undergone vitreous surgery for idiopathic macular holes (MH, n = 14), proliferative diabetic retinopathy (PDR, n = 14), idiopathic epiretinal membranes (ERM, n = 13), and rhegmatogenous retinal detachment (RRD, n = 13). RESULTS: Chymase activities in the vitreous from patients with MH, PDR, ERM, and RRD were 1.87 +/- 0.53, 0.06 +/- 0.04, 0.40 +/- 0.12, and 0.08 +/- 0.03 (mean +/- SE) mU/mg protein, respectively, and ACE activities in the vitreous humor were 0.18 +/- 0.09, 0.30 +/- 0.07, 0.01 +/- 0.01, and 0.03 +/- 0.02 (mean +/- SE) mU/mg protein, respectively. Chymase activity was significantly elevated in MH among these diseases (p < 0.01, Scheffe), and ACE was significantly activated in PDR compared to ERM and RRD (p < 0.05, Scheffe). CONCLUSIONS: Our results suggest that two different angiotensin II generating systems are activated in human vitreous humor; an increased activity of chymase may play a possible role in the formation of macular holes.

Aged↗

Pathogenesis of idiopathic scoliosis: SEPs in chicken with experimentally induced scoliosis and in patients with idiopathic scoliosis.

We studied somatosensory evoked potentials (SEPs) in 20 chickens with experimentally induced scoliosis after pinealectomy and in 100 patients with idiopathic scoliosis. We also studied 20 chickens without scoliosis and 20 healthy youngsters. In the chickens, SEPs after leg stimulation was significantly delayed in the scoliosis group compared to the controls. In patients, the latency of cortical potential (N37) after stimulation of tibial nerve was longer in the scoliosis group than in the controls. Our findings in both experimental and clinical studies strongly support the hypothesis that idiopathic scoliosis results from dysfunction in the central nervous system. The type of SEPs abnormalities described in idiopathic scoliosis suggest a pathology from the midbrain to the cortex.

Adolescent↗

Distribution and isoform characterization of type XII collagen in bovine cornea.

Streptavidin peroxidase immunohistochemistry and immunoelectron microscopy were used to determine the localization of type XII collagen in sections from bovine corneas. Type XII collagen extracted from bovine cornea and skin was assayed by Western blotting. Immunohistochemical experiments showed that type XII collagen was restricted to the corneal stroma; it was not present in corneal epithelium, epithelial basement membrane, Descemet's membrane or endothelium. Type XII collagen was distributed throughout the corneal stroma, and it was prominently localized at the superficial stroma. Immunoelectron-microscopic examination demonstrated that type XII collagen was regularly found along the surface of banded collagen fibrils with a periodic distribution. By Western blot analysis, we observed that extracts from bovine cornea contained both the long and short isoforms of type XII collagen, whereas extracts from bovine skin contained only the short isoform. The homogeneous distribution and/or presence of the long isoform of type XII collagen may be related to the characteristically regular arrangement of collagen fibrils and thereby the transparency of corneal tissue.

Animals↗

Effect of heat-pretreatment on interleukin-2-activated killer cells for in vitro purging.

OBJECTIVE: Lymphokine-activated killer activity is effective in purging residual malignant cells from autologous bone marrow (BM) or leukapheresis collections for peripheral blood progenitor cells (PBPC). In this study, the effect of additional heat pretreatment on IL-2-activated cytotoxicity was examined. METHODS: Nonadherent mononuclear cells from peripheral blood (PB), PBPC collections or BM were exposed to the desired temperature for 1 h, and successively cultured for 7 days in the presence of 1,000 units/ml of recombinant human interleukin-2 (IL-2). Cytotoxicity of IL-2-activated cells was determined by flow cytometry, using PKH-26-labelled K-562 or Raji target cells, and the cell surface antigens were also analyzed. RESULTS: IL-2-activated cells from all specimens showed a distinct generation of cytotoxic activities. The activities were significantly decreased by heat at 42 degrees C, but not changed by heat pretreatment at 40 degrees C. In the surface expression of IL-2-activated cells, the increase of CD56+ cells from PB, PBPC collections and the decrease of CD28 cells from PBPC collections were shown to be significant (p < 0.05), but these changes were not found when the cells were heat-pretreated at 42 degrees C. DISCUSSION: These results suggested that a tumor-killing therapeutic temperature (> or =42 degrees C) may lead to a disadvantage in posttransplantation immunity, and that this reduction of IL-2-activated cytotoxicity may partly be due to a lack of the enhancement of CD56+ cells or the reduction of CD28+ cells.

Antigens, CD↗

Small cell carcinoma of the bladder. Two cases diagnosed by urinary cytology.

BACKGROUND: Primary small cell carcinoma (SCC) of the bladder is a rare but important entity. We report two cases of SCC of the bladder diagnosed by urinary cytology. CASES: A 71-year-old male (case 1) and a 79-year-old female (case 2) presented with asymptomatic gross hematuria. Urinary cytology in case 1 showed the presence of a few undifferentiated malignant small cells and many transitional cell carcinoma (TCC) cells with a bloody and necrotic background. The former cells were small and round, with naked, hyperchromatic nuclei and finely granular chromatin. Pathologic diagnosis after total cystectomy was TCC > SCC > adenocarcinoma, T2M0N0. Urinary cytology of case 2 showed the presence of many undifferentiated malignant small cells and many TCC cells with or without squamous metaplasia. Cytologic features of the former cells were almost the same as those in case 1. Moreover, these cells were neuroendocrine marker positive by immunocytochemistry. Pathologic diagnosis after tumor resection was SCC and TCC > squamous cell carcinoma, T1b. CONCLUSION: The prognosis of primary SCC of the bladder is usually poor. Because our cases were found by urinary cytology at a relatively early stage, both have been well, without any evidence of recurrence, 30 and 25 months after surgery even without adjuvant therapy.

Aged↗

Highly potent and specific inhibitors of human renin.

Small peptide analogues representing the C-terminal portion of angiotensin I sequence were designed as inhibitors of human renin. Among synthesized compounds, benzyloxycarbonyl (-"Z")-(1-naphthyl)Ala-His-leucinal (ES-188), Z-(1-naphthyl)Ala-His-statine ethyl ester (ES-226), and Z-(1-naphthyl)Ala-His-statine 2-methylbutylamide (ES-254) markedly inhibited human and primate renins (inhibitory concentration, 50% [IC50], near 10(-7) M). These peptide analogues inhibited rabbit renin with one or two orders of magnitude less potency. They were very weak inhibitors of renins from pig, goat, dog, and rat. ES-188 had no discernible effect on cathepsin D, pepsin, or human angiotensin-converting enzyme at the concentration of 10(-4)M. ES-226 had little effect on the three enzymes at the concentration of 10(-5)M; however, ES-254 had a considerable inhibitory effect on cathepsin D (IC50 of 1.4 X 10(-5)M), pepsin (IC50 of 4.2 X 10(-5)M), and human angiotensin-converting enzyme (IC50 of 7.1 X 10(-6)M). Our results indicate that 1-naphthylalanine-containing tripeptide analogues are highly potent human renin inhibitors.

Angiotensin I↗

Effects of changing the type of H2-blocker in the treatment of H2-blocker-resistant ulcers: comparison of roxatidine acetate hydrochloride and other H2-blockers.

The efficacy of switching from one type of H2-receptor antagonist (H2-blocker) to another, in the treatment of H2-blocker-resistant ulcers was investigated using H2-blockers with five-membered rings (five-membered-ring agents)--such as cimetidine, ranitidine and famotidine--and an H2-blocker with a six-membered ring, roxatidine. By switching from a five-membered-ring agent to roxatidine in the treatment of five-membered-ring resistant ulcers (study I), gastric ulcers were healed in nine of 19 patients (47%) and duodenal ulcers were healed in eight of nine patients (89%). By switching from roxatidine to one of the five-membered-ring agents in the treatment of roxatidine-resistant ulcers (study II), gastric ulcer was healed in six of 15 patients (40%), and duodenal ulcer was healed in 4 of 10 patients (40%). Particularly in the case of duodenal ulcers, the switch to treatment with roxatidine, which has a different chemical structure from the five-membered-ring agents, may be useful in the treatment of five-membered-ring-resistant ulcers.

Adult↗

Gamma/delta T-cell receptor type granular lymphocyte proliferative disorder associated with rheumatoid arthritis.

We present here a case report of a 69-year-old female patient with T granular lymphocyte proliferative disorder (T-GLPD) expressing the gamma/delta T-cell receptor. The patient had been treated for rheumatoid arthritis for 25 years, and presented with mild anaemia. Cell-surface marker analysis was carried out using flow cytometry and natural killer function was determined using a chromium release assay. The case report is followed by a summary of the 21 other gamma/delta T-GLPD cases reported in the literature and a comparison of their clinical characteristics with those of T-GLPD cases expressing the alpha/beta T-cell receptor. The clinical symptoms and the frequency of association with rheumatoid arthritis are similar in gamma/delta and alpha/beta T-GLPD, but a prevalence of the CD8- cell-surface marker and enhanced natural killer function appear to be characteristics of gamma/delta T-GLPD.

Aged↗

A case of primary hypoparathyroidism complicated by heart failure.

We report a case of hypocalcemic heart failure without underlying myocardial disease. Two-dimensional and Doppler echocardiography revealed dilatation and impaired contraction of the left ventricle, but did not show any valvular dysfunction. Cardiac catheterization showed a normal coronary artery, and cardiac muscle biopsy showed morphological changes in mitochondoria and endoplasmic reticulum, which may be due to metabolic changes. This patient was asymptomatic after the serum calcium concentration was normalized.

Aged↗

A comparison of hepatocellular carcinoma associated with HBV or HCV infection.

BACKGROUND/AIMS: Close relationships between hepatocellular carcinoma (HCC) and hepatitis virus infection have been elucidated. However, clinical differences between HBV- and HCV-associated HCC remain unclear. METHODOLOGY: Four hundred and sixteen patients with HCC were examined for both HBsAg and HCV-Ab. Sixty-nine of the 416 patients (16.6%) were positive for HBsAg and negative for HCV-Ab (B-HCC), while 290 patients (69.7%) were negative for HBsAg and positive for HCV-Ab (C-HCC). Various comparisons were made between the 2 groups. RESULTS: B-HCC patients were younger in age (p < 0.0001), and had significantly better liver function than C-HCC patients. The motivation of HCC detection was different between the 2 groups (p < 0.0001), and the tumor size of B-HCC was significantly larger when comparing groups with regard to symptoms (p < 0.05). Although B-HCC demonstrated better survival in Stage I/II treated by surgery (p < 0.05), it was associated with poorer survival in Stage III/IV receiving hepatic arterial infusion chemotherapy when compared to C-HCC (p < 0.01). CONCLUSIONS: These results suggest that clinical differences between B-HCC and C-HCC may depend upon the difference of the natural course between HBV and HCV infection, and B-HCC may be more resistant to treatment than C-HCC in the advanced stage. This also illustrates the need for early tumor detection in B-HCC.

Carcinoma, Hepatocellular↗

Small cell carcinoma of the gallbladder: a case report and review of 53 cases in the literature.

Although small cell carcinoma of the gallbladder is rare, the prognosis of this tumor type is poorer than that of differentiated carcinomas. We report herein the case of a 62-year-old man with small cell carcinoma of the gallbladder. The operative findings showed an unresectable large tumor of the gallbladder and multiple metastases involving the liver and lymph nodes. Pathological findings revealed small sized carcinoma cells, round or oval in shape which displayed a cord-like or solid appearance. Diagnosis was confirmed by ultrastructural study that showed the presence of neurosecretory-type cored granules. He was treated by intraarterial chemotherapy with cisplatin and etoposide. Six months later, abdominal computed tomography scan confirmed loss of the large mass. A complete response to the chemotherapy was noted over a period of six months, suggesting the efficacy of intraarterial chemotherapy for this disease. Fifty-three cases of small cell carcinoma reported in the English literature are reviewed. In most cases, including ours, a radical operation was not indicated and the prognosis was extremely poor, due to the difficulty of early diagnosis and the rapid progression of the disease. Chemotherapy is effective in general and intraarterial chemotherapy performed in the present case may be particularly useful to improve survival.

Antineoplastic Combined Chemotherapy Protocols↗

Detection of non-papillary, non-invasive transitional cell G1 carcinoma as revealed by increased DNA instability and other cancer markers.

The method to reveal DNA-instability as demonstrated by immunohistochemical staining with anti-cytidine antibody after acid hydrolysis (DNA-instability test) was used as a marker of malignancy. The test was applied to paraffin-embedded sections taken from 15 urinary bladders, renal pelvic cavities, and ureters bearing multiple carcinoma in situ (CIS) and totally 31 papillary urothelial cancers. The serial sections of the same tissues were also subjected to immunohistochemical staining for PCNA, p53, DFF45, and VEGF. The DNA-instability test was positive in 100% cancer lesions irrespective of the grades, and apparently normal urothelium, and hyperplastic and dysplastic urothelial lesions also showed the areas with clones positively stained with DNA-instability testing, and the percent numbers of positive areas in them were 28.3%, 37.7%, and 61.5%, respectively. These clones, which were present in apparently normal urothelium and in hyperplastic and dysplastic urothelial lesions, showed higher percent values of PCNA-positive-cells, in comparison to the values estimated in the areas with negatively stained DNA-instability testing, and the former values were statistically not different from those in carcinoma lesions. Furthermore, the percent numbers of areas positive for p53, DFF45, and VEGF, with positive DNA-instability testing were also much higher than those with negative DNA-instability testing in apparently normal urothelium, and hyperplastic and dysplastic urothelial lesions, and the former values were again comparable to those in cancer lesions with no statistical differences. These clones were regarded as already being malignant and should be the direct precursors of progressed cancer lesions. They will make progression through two different pathways, one to papillary non-invasive G1 cancers by neovascularization induced by paracrine secretion of VEGF, and another to flat CIS G2 without secretion of VEGF; thus the clones should be regarded as non-papillary, non-invasive Gl TCC, or CIS G1. It should be always taken into account that the probability for apparently normal urothelium, and hyperplastic and dysplastic urothelial lesions to contain cancer clones, will be high already, especially in tumor-bearing bladders.

Biomarkers, Tumor↗

Pathogenesis of calcium crystal deposition in the ligamentum flavum correlates with lumbar spinal canal stenosis.

OBJECTIVE: To investigate the histological and immunohistochemical properties of degenerative changes and calcium crystal deposition in the lumbar ligamentum favum. METHODS: We examined the ligamentum flavum harvested from 119 surgical cases with symptomatic lumbar spinal stenosis. Sections of the ligament were examined by scanning electron microscopy (SEM), energy dispersive X-ray micro-analysis, and were immunostained for S-100 protein, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and CD34. The results were compared with those of ligament tissue harvested from 10 cases of lumbar disc herniation. RESULT: The elastic fibres of the ligamentum favum showed regular, or sometimes irregular, and fragmented fibre bundles. Large areas of fibrosis with reduced elastic component and increased collagenous tissue were frequently seen in the degenerated ligaments. Calcium crystal deposits were observed in these fibrous ligaments, associated with many hypertrophic chondrocytes, and with small blood vessel formation. These chondrocytes stained positively for S-100 protein, VEGF and bFGF Calcium pyrophosphate dihydrate crystals were identified in the calcium deposit area. CONCLUSION: We believe that rupture of elastic fibre bundles is the first change to occur in degeneration of the ligamentum favum. Calcium crystal deposition was seen within these fibrous and chondrometaplastic areas. Hypertrophic chondrocytes regulate crystal formation and tissue reconstruction by secreting cytokines.

Adult↗

Hypoglycemic action and disposition of gliclazide in normal and analbuminemic rats.

The hypoglycemic action and disposition of gliclazide, an oral antidiabetic drug, was investigated in normal and analbuminemic rats. Orally administered gliclazide exhibited a stronger hypoglycemic action in analbuminemic rats than in normal rats. However, the plasma concentration of the drug in the mutant was much lower than that in the normal. This apparent discrepancy may be clarified by measuring the plasma concentration of unbound gliclazide. Analbuminemic rats gave larger values for the total body clearance and steady state volume of distribution of gliclazide than normal rats. The biliary and urinary excretion rates of radioactivity after intravenous bolus administration of [3H]-gliclazide were much greater in the mutant than in the normal. The binding of gliclazide to serum in analbuminemic rats was much lower than that in normal rats. Furthermore, the radioactivities of some tissues after oral administration of [3H]-gliclazide were found to be significantly higher in the mutant than in the normal. These results clearly indicate that albumin plays an important role in the hypoglycemic activity and disposition of gliclazide in rats.

Animals↗