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Biomedical subjects

H Uno

Publications and source records attributed to H Uno.

At least 91 records · Page 5Linked to original sources
PubMed1995

Removal of LDL from plasma by adsorption reduces adhesion molecules on mononuclear cells in patients with arteriosclerosis obliterans.

BACKGROUND: There is increasing evidence that immune processes are important in the development of atherosclerosis. We investigated whether low density lipoprotein (LDL) adsorption therapy affected serum cytokine levels and the expression of adhesion molecules on peripheral blood mononuclear cells (lymphocytes and monocytes) in patients with arteriosclerotic obliterance (ASO). METHODS AND RESULTS: LDL adsorption therapy was repeated ten times over a period of three months in ten ASO patients. The total serum cholesterol and LDL cholesterol levels were significantly reduced at the end of therapy. This was associated with a significant improvement in Fontaine's classification and ankle pressure index. We also measured serum levels of inflammatory cytokines (interleukin-1 beta (IL-1 beta), IL-6 and tissue necrosis factor alpha (TNF-alpha)) and expression of adhesion molecules (lymphocyte function-associated antigen 1 alpha (LFA-1 alpha), LFA-1 beta, CD2, very late antigen (VLA)-4, VLA-5 and CD44) on mononuclear cells in the same patients and a group of healthy subjects. Serum levels of all inflammatory cytokines were markedly higher in ASO patients compared with healthy subjects, but there was no significant difference in the level before and after LDL adsorption. VLA-4 expression on CD3+ cells, but not of other adhesion molecules, was markedly higher in ASO patients compared with healthy subjects. LDL adsorption caused a significant reduction in CD2, VLA4 and VLA-5 expression on CD3+ cells. Furthermore, VLA-4 and VLA-5 expression on monocytes diminished significantly after LDL adsorption. CONCLUSIONS: Our results indicate that LDL adsorption-induced immunoregulation is mediated by an indirect stimulatory effect on the immune system. The results suggests that improved peripheral circulation produced by LDL adsorption may reflect improved immune dysfunctions of atherosclerotic lesions in ASO patients.

Aged↗
PubMed1995

Corticotropin-releasing factor (CRF) receptors in infant rhesus monkey brain and pituitary gland: biochemical characterization and autoradiographic localization.

A large body of data suggests that the corticotropin-releasing factor (CRF) system serves to coordinate the autonomic, endocrine, immune and behavioral aspects of the stress response. In rats, the distribution of CRF receptors in brain and pituitary has been well characterized, however, little information is available in primates. In this study, CRF receptors were characterized by radioligand binding and localized using autoradiography with [125I]-oCRF in the pituitary gland and in discrete brain regions of 2-week-old, 12-week-old and adult rhesus monkeys. Autoradiographic localization studies in slide-mounted tissue sections in the 2- and 12-week-old monkeys demonstrated high CRF receptor densities in both anterior and intermediate lobes of the pituitary as well as in discrete regions of the brain. The distribution of CRF receptors in the anterior pituitary demonstrated a 'cluster-like' appearance reminiscent of corticotrope distribution. In contrast, receptors in the intermediate lobe were more uniformly distributed. No significant differences were evident in the pattern of localization or the number of CRF receptors in the pituitaries of 2- compared to 12-week-old animals. However, marked differences were observed in the dentate gyrus of the hippocampus. Receptors in this region were absent in 1- to 2-week old animals but quite dense by 11-12 weeks of age. Conversely, in the lateral and medial geniculate nuclei, high levels of CRF receptors were identified early in life that virtually disappeared by 11-12 weeks of age. Thus, there is considerable correspondence in the development of the CRF system between the rat and rhesus monkey and this presents further evidence for the functional role of this peptide in brain development.

Animals↗
PubMed1995

Observation of T cell surface antigens in the clinical course of adult T-cell leukemia: case report of a spontaneous remission.

A patient with acute adult T-cell leukemia (ATL) in whom spontaneous remission was observed without any specific treatment having been given is described. The abnormal cell phenotype was CD4+, CD45RO+ and CD8-. As the number of abnormal cells decreased, CD4+ cell count decreased and CD8+ cells and CD45RA+ cells increased to normal levels (45 and 77%, respectively). Further, the number of cells with CD45RO antigen of intermediate fluorescence intensity increased. Five months after admission, we assessed the patient as being in a state of complete clinical remission; no abnormal cells were detected in peripheral blood, lymph node enlargement had disappeared and the serum chemistry was normal. When the abnormal cells in peripheral blood had disappeared, Southern blot analysis for HTLV-I proviral DNA still revealed a weak monoclonal band with EcoRI digestion, and HTLV-I proviral DNA was detected by polymerase chain reaction analysis. Thus, it appeared that very few abnormal cells persisted although the laboratory findings for ATL were normal. Our case could contribute to the understanding of the mechanism that underlies spontaneous remission in ATL.

Adult↗
PubMed1995

Prostate cancer-induced oncogenic hypophosphatemic osteomalacia.

A 65-year-old male with prostate carcinoma showed mild hypocalcemia of 7.9 mg/dl, marked hypophosphatemia of 1.7 mg/dl, hyperphosphaturia (tubular reabsorption of phosphorus 43% and tubular threshold for phosphorus of 0.6 mg/dl), low serum 1,25 (OH)2D level of less than 5 pg/ml and osteomalacia indicated by a marked increase of relative osteoid volume and fractional formation rate in the undecalcified section. Oncogenic osteomalacia due to prostatic carcinoma with suppression of 1,25 (OH)2D production and phosphaturia was suggested.

Adenocarcinoma↗
PubMed1995

Collaborative work to determine the optimal administration period and parameters to detect drug effects on male rat fertility--study on estradiol benzoate effects.

In order to examine the optimal administration period and parameters for male fertility assessment, male rats were subcutaneously administered 0.2, 2 or 20 micrograms/kg of estradiol benzoate (E2B), a known testicular toxicant, for 4 weeks or 9 weeks before mating. After 4 weeks administration, suppression of body weight gain and food consumption, decreases in prostate and seminal vesicle weights, atrophy of Leydig cells, and mature spermatid retention at stages IX, X and XI were observed in the 2 and 20 micrograms/kg groups. In the 20, micrograms/kg group, decreases in epididymides weight and copulation index were also found but the number of sperm and sperm motility were not affected. In the 0.2 micrograms/kg group, no changes were noted in any parameters. After 9 weeks administration, decreases in testis weight and the number and motility of sperm were observed in the 20, micrograms/kg group, in addition to the changes found after 4 weeks administration. These results suggest that detailed histopathological evaluation and determination of accessory sex organ weights are sensitive for evaluating the effects of E2B on male fertility. Results with the 4-weeks treatment were comparable to those with the 9-weeks treatment in terms of these parameters.

Animals↗
PubMed1995

Smoldering adult T-cell leukemia with B-cell lymphoma and early gastric cancer.

We report a case of smoldering adult T-cell leukemia (ATL) with B-cell lymphoma and early gastric cancer. A 64-year-old man was admitted to our hospital because of proteinuria and hypergammaglobulinemia. Systemic lymphadenopathy, "flower cells" in peripheral white blood cells, and hypergammaglobulinemia with monoclonal gammopathy (IgA, lambda type) were found. As Southern blot analysis revealed monoclonal integration of human T-lymphotrophic virus type I proviral DNA in peripheral blood mononuclear cells, he was diagnosed as having smoldering ATL. The tissue specimen of an inguinal lymph node showed proliferation of abnormal lymphocytes which were stained with anti-lambda antibody, indicating B-cell lymphoma. A polypoid lesion in the stomach was histologically diagnosed as early gastric cancer.

HTLV-I Infections↗
PubMed1995

Brain metastasis from malignant mesothelioma--case report.

A 62-year-old male presented with a rare brain metastasis from malignant mesothelioma manifesting as headache and progressive left hemiparesis. He had previously undergone pleurectomy for malignant mesothelioma. Chest x-ray films showed no recurrence of mesothelioma. Computed tomography and magnetic resonance imaging revealed a homogeneously enhanced nodular mass adjacent to the falx in the right frontal lobe. The tumor was totally removed and diagnosed histologically as brain metastasis from malignant mesothelioma. Following surgery, left hemiparesis improved gradually. Brain metastasis from malignant mesothelioma is usually discovered in the terminal stage or at autopsy. Surgical removal and radiotherapy should be considered for isolated lesions.

Brain Neoplasms↗
PubMed1995

[Clinical significance of PSA-density in differential diagnosis between BPH and early stages prostate cancer].

OBJECT: In differential diagnosis of BPH and early stages prostate cancer (PC), PSA-density (PSAD) was evaluated in 63 cases with BPH and 82 cases of PC (stage A: 8, B: 17, C: 17, D: 40). METHODS: Serum PSA values were determined by MARKIT-F PA, and prostate volume was calculated by transabdominal ultrasonography, in which every glands including peripheral zone was visualized in the transverse and sagittal planes, and predicted prostate volume was calculated by three dimension (a x b x c x 0.52). PSAD was determined by serum PSA divided by prostate volume. RESULTS: PSAD values were 0.106 +/- 0.006 (mean +/- SD) in BPH, 0.538 +/- 0.094 in stage A and B of PC, and 2.973 +/- 0.764 in all PC cases. There was a statistical significance (p < 0.005) between BPH and each other groups of PC by student's t-test. In using 0.208 (mean +/- 2 SD of PSAD in BPH group) as a cut-off value, the detection sensitivity was 84% in stage A and B of PC and the specificity was 97% using BPH groups as a control, therefore the efficacy was 93%. In 18 out of 19 cases with BPH having PSA values more than 3.6 ng/ml (false positive group), PSAD values were less than 0.208. CONCLUSION: PSAD is suggested to be a useful tool for differential diagnosis of BPH and early stages of PC.

Aged↗
PubMed1995

[Antitumor effect of MX2, a new morpholino anthracycline against C6 glioma cells and its combination effect with photodynamic therapy in vitro].

MX2, a new lipophilic morpholino anthracycline, has been reported to have superior chemotherapeutic effects to adriamycin against murine and human tumor cells. In this study the chemotherapeutic effect of MX2 against C6 glioma cells was examined as well as the photocytotoxicity of MX2 and the combination effect of MX2 and photodynamic therapy (PDT) in vitro. Colony formation is inhibited even with only 2 hour treatment with MX2 in a dose-dependent manner. In this colony forming efficiency assay the drug concentration required for 50% inhibition of colony formation for C6 glioma cells was 24.0 +/- 4.5 ng/ml. Mild photocytotoxicity of MX2 against C6 glioma cells was observed at a high concentration (100 ng/ml) of MX2 following exposure to white light but not red light. In combination, MX2 and the photosensitizer haematoporphyrin derivative (HpD) exhibited an additive cytotoxic effect against C6 glioma cells when the cells were treated with MX2 either immediately after red light illumination following incubation with HpD or at an interval of 24 hours before incubation with HpD. We conclude that MX2 may be clinically useful against malignant glioma alone, and in combination with other therapies such as PDT.

Animals↗
PubMed1995

Altered expression of class I HLA antigen on peripheral mononuclear cells in patients with adult T-cell leukemia: inverse relationship with natural killer susceptibility.

Patients with adult T-cell leukemia showed altered expression of class I HLA antigen in their peripheral blood lymphocytes. Acute type adult T-cell leukemia showed increased levels of the antigen expression compared to those of control group and smoldering type (P < 0.001 and 0.01, respectively). Natural killer sensitivity of infected cell lines with different levels of class I HLA expression showed an inverse relationship with the antigen expression. Further, various cell lines including human T-cell leukemia virus type I-infected cell lines treated with acid buffer, which selectively eliminated the surface class I HLA molecules from cell membrane, became more sensitive to natural killer-mediated lysis. These data suggested that the enhanced expression of class I HLA on peripheral blood lymphocytes of patients with acute type adult T-cell leukemia may contribute to escaping from the immunosurveillance system of natural killer cells in vivo.

Adult↗
PubMed1995

Effect of clenbuterol on sulfur dioxide-induced acute bronchitis in guinea pigs.

When guinea pigs were exposed to sulfur dioxide (SO2) gas (800 ppm, 2 h), they showed hyperresponsiveness to intravenously administered serotonin (5-hydroxytryptamine (5-HT)). This hyperresponsiveness continued for over 24 h after the exposure to the gas. The degeneration, desquamation of epithelium, and edema of the lamina propria of the trachea and bronchi were observed in animals after a 2-h exposure of SO2 histopathologically. These changes seemed to be the early phase of acute bronchitis. Then, we examined the effect of clenbuterol, a selective beta-2 adrenoceptor agonist, on the SO2-induced bronchial hyperresponsiveness in these animals. Orally administered clenbuterol (1-10 micrograms/kg) suppressed the hyperresponsiveness to 5-HT in a dose-dependent manner. These results suggest that clenbuterol might inhibit the hyperresponsiveness that accompanies acute bronchitis and that this agent may be useful for remission of broncho-spasm.

Acute Disease↗
PubMed1995

[Pharyngeal metastasis and arteriovenous fistula of renal cell carcinoma--report of a case].

A 76-year-old Japanese male consulted our hospital complaining of dysphagia. He also complained of dyspnea, and a cardiovascular disorder was detected. Otolaryngological examination revealed dysphagia due to pharyngeal tumor. Further examination detected left renal cell carcinoma with multiple pulmonary metastasis, and selective angiography revealed arteriovenous fistula in the primary tumor. After resection of the pharyngeal tumor and left nephrectomy, pharyngeal tumor was pathologically confirmed as metastasis of renal cell carcinoma. Furthermore, after left nephrectomy, the cardiovascular disorder gradually improved. Thus, the cardiovascular disorder was considered to have developed based upon the arteriovenous fistulae. Pharyngeal metastasis of renal cell carcinoma is extremely rare, and the cardiovascular disorder in this case was also an extrarenal manifestation.

Aged↗
PubMed1995

[Study on prognostic factors in twenty-five patients with myelodysplastic syndrome].

Twenty-five consecutive patients with myelodysplastic syndrome (MDS) were followed in the Second Department of Internal Medicine, Miyazaki Medical School from 1984 to 1993. The diagnosis of MDS was morphologically based on the criteria of FAB. At the time of diagnosis, 9 patients had refractory anemia (RA), 1 had RA with ring sideroblasts (RARS), 6 had RA with excess blasts (RAEB), 6 had RAEB in transformation (RAEB-t), and 3 had chronic myelomonocytic leukemia (CMMoL). Prognostic factors involved in survival times and progression to leukemia were analyzed in these patients; FAB classification of MDS, age, sex, peripheral blood cell counts, bone marrow examination, karyotype, numbers of blasts. None of these prognostic factors had a significant effect on the prognosis of MDS patients. Study of the therapeutic effects on MDS patients revealed no significant increase of survival time in treated MDS patients compared to non-treated patients. Further, no significant difference in survival time was found between MDS patients treated with or without anticancer drugs. These results indicated that MDS patients were pathologically and therapeutically heterogeneous.

Aged↗
PubMed1995

[Acute necrotizing gastritis associated with adult T-cell leukemia in the course of chemotherapy].

A 63-year-old man with smoldering adult T-cell leukemia (ATL) which became acute was admitted. During chemotherapy, he experienced epigastric pain and fever due to neutropenia. The combination therapy of antimicrobials and rhG-CSF was ineffective and he died. Autopsy revealed systemic invasion of ATL cells. The stomach findings resembled those of phlegmonous gastritis, a rare form of bacterial gastritis, along with diffuse, mucosal necrosis with hemorrhage. The pathogenesis of necrotizing gastritis remains to be elucidated. The patient had also received histamine H2 antagonist for gastric ulceration, which might have influenced the gastric bacterial flora.

Aged↗
PubMed1995

[Evaluation of gastric adaptive relaxation in isolated stomach from the guinea-pig].

To evaluate the mechanism of gastric adaptive relaxation (GAR), we designed and established the experimental system for the measurement of GAR in isolated stomach from the guinea-pig by modifying the method of Desai. We also investigated the roles of non-adrenergic, non-cholinergic (NANC) nerves and endogenous nitric oxide (NO) in GAR by using this system. The rapid increase in the capacity of isolated stomach was observed over a certain pressure as GAR. GAR was abolished by tetrodotoxin (10(-6) M) in the presence of atropine (3 x 10(-6) M) and guanethidine (5 x 10(-6) M). NG-nitro L-arginine (LNNA) (10(-4) M), a NO synthesis inhibitor, also abolished GAR. L-arginine (10(-3) M), a precursor for NO synthesis, reversed LNNA-induced impairment of GAR. Sodium nitroprusside (10(-6)-10(-4) M), a NO-donor, induced the gastric relaxation. These results suggest that GAR is mediated by NANC nerves, possibly via endogenous NO.

Adaptation, Physiological↗
PubMed1995

Effects of endothelin on serum gastrin level and acid secretion in rats.

Endothelin (ET) is a potent ulcerogen in gastric mucosa. Disordered microcirculation due to vasoconstriction may cause gastric mucosal injury. In a previous study we found ET in gastric mucosal cells, especially chief cells and endocrine cells, and in vascular endothelial cells. Most endocrine cells staining for ET-1 are G cells. This study was done to find whether ET affects G-cell function, particularly gastrin release and acid secretion. ET-1 or ET-3 (5 nmol/kg) was injected i.v. into male Wistar rats. Blood samples were collected just before and 15, 30, or 60 min after injection and serum gastrin levels were assayed by RIA. The effects of BQ123-Na (Banyu), an ET receptor antagonist, pirenzepin, or an intragastric pH of 2 on changes in the gastrin levels brought about by ET-1 were examined. The gastric contents of rats with the pylorus ligated were collected for 1 h and then for the next 4 h after the ET-1 injection, and the acid output was calculated. After ET-1 administration, the gastric mucosa of the pyloric gland area was immunostained with antigastrin. The serum gastrin levels at 15, 30, and 60 min after ET-1 injection (220 +/- 94, 204 +/- 77, and 366 +/- 191 pg/ml, respectively) were significantly higher than those before the injection (75 +/- 18 pg/ml). ET-1 decreased the number of cells stained for gastrin. ET-3 had no effect on gastrin levels. BQ123-Na inhibited the increase in gastrin caused by ET-1, but pirenzepin had no effect. At pH 2, ET-1 had no effect on gastrin. ET-1 decreased acid output (2.6 +/- 2.3 microEq/h and 239 +/- 80 microEq/4 h, respectively) vs. controls (63 +/- 55 microEq/h and 346 +/- 81 microEq/4 h). Therefore, ET-1 increases rat serum gastrin levels, an effect that may be related to its reduction of acidity.

Animals↗
PubMed1994

Neurotoxicity of glucocorticoids in the primate brain.

Severe and prolonged physical and psychological stress is known to cause brain damage; long-term torture victims in prison have later developed psychiatric disorders and cerebral cortical atrophy observed in CT scans (Jensen, Genefke, Hyldebrandt, Pedersen, Petersen, and Weile, 1982). In nonhuman primates, we observed degeneration and depletion of the hippocampal neurons in African green monkeys that had been severely abused by cagemates and died with complications of multiple gastric ulcers and adrenal cortical hyperplasia (Uno, Tarara, Else, Suleman and Sapolsky, 1989). In our previous studies the administration of dexamethasone (DEX) (5 mg/kg) to pregnant rhesus monkeys at 132 to 133 days of gestation induced degeneration and depletion of the hippocampal pyramidal and dentate granular neurons in the brains of 135-gestation-day fetuses, and these changes were retained in the brains of fetuses at near term, 165 days of gestation (Uno, Lohmiller, Thieme, Kemnitz, Engle, Roecker, and Farrell, 1990). We also found that implantation of a cortisol pellet in the vicinity of the hippocampus in adult vervet monkeys induced degeneration of the CA3 pyramidal neurons and their dendritic branches (Sapolsky, Uno, Rebert, and Finch, 1990). Thus, hippocampal pyramidal neurons containing a high concentration of glucocorticoid receptors appear to be highly vulnerable to either hypercortisolemia caused by severe stress or to exposure to exogenous glucocorticoids. To study the long-term postnatal sequelae of prenatal brain damage, eight rhesus monkeys were treated with either DEX (5 mg/kg), 5 animals, or vehicle, 3 animals, at 132 to 133 days of gestation. After natural birth, all animals lived with their mothers for 1 year. At 9 months of age, we found that DEX-treated animals had significantly high plasma cortisol at both base and post-stress (isolation) levels compared to age-matched vehicle-treated animals. Magnetic resonance images (MRI) of the brain at 20 months of age showed an approximately 30% reduction in size and segmental volumes of the hippocampus in DEX-treated compared to vehicle-treated animals. Measurements of whole brain volume by MRI showed no significant differences between DEX and vehicle groups. Prenatal administration of a potent glucocorticoid (DEX) induced an irreversible deficiency of the hippocampal neurons and high plasma cortisol at the circadian baseline and post-stress levels in juvenile rhesus monkeys. These results suggest that the hippocampus mediates negative feedback of cortisol release; a lack or deficiency of the hippocampal neurons attenuates this feedback resulting in hypercortisolemia.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗