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Biomedical subjects

H Uno

Publications and source records attributed to H Uno.

At least 73 records · Page 4Linked to original sources

[Diagnosis and follow-up of prostate cancer patients using prostate specific antigen (PSA)].

An international standard of prostate specific antigen (PSA) assays was constructed and prognosis of the patients with prostate cancers showing gray zone PSA was studied. For lower levels of serum PSA (< 50 ng/ml), the conversion formula to that of Tandem-R PSA from other assays was presented. Furthermore, based on the standards of Stanford Reference and Markit-MPA, conversion rates to this international standard from the conventional PSA assays were also obtained. Patients' cancer-specific survival was found to be significantly better in the gray zone group. Further studies to obtain higher specificity such as using free or complex rate in total PSA is necessary.

Follow-Up Studies↗

Difference in selectivity to song note properties between the vocal nuclei of the zebra finch.

Responses to a single note from a zebra finch song and an artificially modified note were recorded from neurons in the vocal nuclei in the zebra finch. Response patterns recorded in the higher vocal center (HVC) and the lateral magnocellular nucleus of the neostriatum (IMAN) were compared. A subset of neurons were found to preferentially respond to the original temporal sequence of the components of the note and/or the specific harmonic structure of the note. These neurons were more common in the IMAN than in the HVC. These results suggest that response selectivity to both the harmonic and temporal pattern of the note increases as auditory information flows from the HVC to the IMAN.

Acoustic Stimulation↗

Whole body positron emission tomography imaging of simian immunodeficiency virus-infected rhesus macaques.

Pathogenesis of simian immunodeficiency virus (SIV) infection in rhesus macaques begins with acute viremia and then progresses to a distributed infection in the solid lymphoid tissues, which is followed by a process of cellular destruction leading to terminal disease and death. Blood and tissue specimens show the progress of infection at the cellular level but do not reveal the pattern of infection and host responses occurring throughout the body. The purpose of this investigation was to determine whether positron emission tomography (PET) imaging with intravenous 2-18F-2-deoxyglucose (FDG) could identify activated lymphoid tissues in a living animal and whether this pattern would reflect the extent of SIV infection. PET images from SIV-infected animals were distinguishable from uninfected controls and revealed a pattern consistent with widespread lymphoid tissue activation. Significant FDG accumulation in colon along with mesenteric and ileocaecal lymph nodes was found in SIV infection, especially during terminal disease stages. Areas of elevated FDG uptake in the PET images were correlated with productive SIV infection using in situ hybridization as a test for virus replication. PET-FDG images of SIV-infected animals correlated sites of virus replication with high FDG accumulation. These data show that the method can be used to evaluate the distribution and activity of infected tissues in a living animal without biopsy. Fewer tissues had high FDG uptake in terminal animals than midstage animals, and both were clearly distinguishable from uninfected animal scans.

Animals↗

Eimeria tenella: role of carbohydrates on sporozoite at the penetration into cultured cells.

The effects of carbohydrates on the penetration of Eimeria tenella sporozoites into cultured cells were investigated. Eight different carbohydrates that have been known to be on the surfaces of animal cells were added to culture medium during the penetration period. D-Galactose alone inhibited sporozoite penetration into primary chicken kidney cells. When kidney cells were pretreated with D-galactose and infected with E. tenella sporozoites, the penetration was suppressed significantly, but not when the sporozoites were pretreated. In addition, the penetration of sporozoites was suppressed when pretreated with peanut lectin that specifically recognizes D-galactose residues at a concentration of 50 micrograms/ml. The present results suggested that D-galactose residues on E. tenella sporozoite surfaces and the lectin-like receptors that recognize D-galactose of host cells are important factors for penetration.

Animals↗

Tacalcitol (1,24(OH)2D3, TV-02) inhibits phorbol ester-induced epidermal proliferation and cutaneous inflammation, and induces epidermal differentiation in mice.

In this study, we examined the cutaneous effects of tacalcitol [1,24(R)(OH)2D3] on epidermal proliferation, differentiation, and skin inflammation in vivo using hairless mice. Tacalcitol was shown to inhibit epidermal proliferation using TPA-induced ornithine decarboxylase activity and DNA synthesis as indices, and the induction of epidermal differentiation using type I transglutaminase activity as an index. Tacalcitol also displayed an antiinflammatory effect on TPA-induced inflammatory changes histopathologically. These results confirm the clinical efficacy of tacalcitol in psoriasis, and suggest that it may be efficacious in the treatment of other inflammatory skin diseases.

Administration, Topical↗

Expression of CD26/dipeptidyl peptidase IV in adult T cell leukemia/lymphoma (ATLL).

The association of CD26/dipeptidyl peptidase IV (DPPIV) and human T lymphotropic virus type I (HTLV-I) was studied by two approaches. First, we examined the expression of CD26 in peripheral blood mononuclear cells (PBMC) from the patients with adult T cell leukemia/lymphoma (ATLL), an HTLV-I-related malignancy. The expression of CD26 on the surface of PBMC was decreased in all 20 patients with ATLL compared with those from normal individuals (P < 0.01) and the expression of the CD26 gene transcript was not detectable in seven out of eight patients with ATLL. Then we compared the quantity of viral DNA in CD26-negative (CD26-) and CD26-positive (CD26+) cells obtained from 17 HTLV-I healthy carries by using a polymerase chain reaction method. The CD26-cells had a higher copy number of viral DNA than CD26+ cells. These findings indicate that HTLV-I has in vivo tropism to CD26- cells, suggesting that some phenotypes of ATLL cells reflect the in vivo cellular tropism of HTLV-I.

Adult↗

MHC class II restriction for T cell proliferative response to mite antigen.

BACKGROUND: We investigated the immunoreguratory role of the major histocompatibility complex in peripheral blood lymphocytes' proliferative response to mite antigen. METHOD: Peripheral blood lymphocytes of Japanese asthmatic patients were incubated with antigen obtained from Dermatophagoides pteronyssinus with a molecular weight of about 15,000, with and without 0.05 microgram/mL of monoclonal antibody against HLA class I or class II for seven days at 37 degrees C humidified in 5% CO2 and 95% air. RESULTS: High and low responders to the mite body antigen were found among the patients while there were no high responders among the healthy individuals tested. In the mite-sensitive asthmatic patients, CD4+ T cells were the population that responded to the antigen. Depletion of CD8+ T cells from the peripheral blood lymphocytes of mite-insensitive individuals caused high responsiveness to the antigen, indicative that the mite-specific CD4+ T cells controlled the high responsiveness and the antigen-specific CD8+ T cells, the low responsiveness. Anti-HLA-DR monoclonal antibody inhibited responsiveness. In contrast, anti-HLA-DQ monoclonal antibody produced high responsiveness in low responders to mite antigen. CONCLUSION: High T cell proliferative responsiveness to mite antigen was restricted by HLA-DR antigen through CD4+ T cells in high responders, whereas HLA-DQ antigen is a restriction antigen of low responsiveness through CD8+ T cells in low responders and non-atopic individuals.

Animals↗

Clinical significance of CD45RO expression on peripheral blood mononuclear cells in HTLV-I-infected individuals.

The phenotype of peripheral blood mononuclear cells (PBMC) was examined in 13 healthy volunteers, 26 HTLV-I carriers, and 58 ATL patients (22 smouldering, five chronic, 24 acute, and seven lymphoma type). The percentage of CD4+, CD25+, CD28+ and CD45RO+ cells in the PBMC of the chronic and acute type patients was significantly higher than that of the volunteers, whereas the percentage of CD8+ and CD45RA+ cells in these patients was significantly low. The histogram for CD45RO fluorescence intensity (FI) revealed two patterns: pattern A consisted of CD45RO+ cells with high FI (CD45ROhigh) and intermediate FI (CD45ROint). Pattern B consisted exclusively of CD45ROhigh. Pattern A was evident in all volunteers. The percentage of subjects showing pattern B was increased in an order that reflected disease progression. In the patients with pattern A, the CD45ROint cells were CD4+ and CD8-, and the FI of CD2, CD3, and Fas within the CD45ROint cells appeared to be lower than that within the CD45ROhigh cells. The acute type patients with pattern A had a significantly longer survival curve than that of these patients with pattern B. These results suggest that the presence of CD45ROint cells may be related to protection against disease progression in HTLV-I-infected individuals.

Acute Disease↗

The effect of thoracic epidural anesthesia on hypoxic pulmonary vasoconstriction in dogs: an analysis of the pressure-flow curve.

The aim of the present study was to examine whether hypoxic pulmonary vasoconstriction (HPV) is preserved during one-lung ventilation combined with thoracic epidural anesthesia (TEA) in dogs. Using a separately ventilated left lower lobe (LLL) in situ, the pressure-flow (P-Q) curve was obtained. The HPV response was assessed by the shift of the P-Q curve, changes in blood flow diversion rate (FDR) and decrease in PaO2 during hypoxic gas ventilation of LLL. In the control group (n = 7), the shift of P-Q curve, changes in FDR, and decrease in PaO2 remained constant during four consecutive hypoxic stimulations. In the TEA group (n = 6), the P-Q curve shifted to the left during hyperoxia, but the magnitude of the shift during hypoxia was unchanged. FDR and decrease in PaO2 were significantly reduced compared with baseline values (P < 0.05 with analysis of variance). TEA reduced heart rate, cardiac output, mean arterial pressure, mean pulmonary arterial pressure, and mixed venous oxygen tension. Our results suggest that TEA did not affect the primary pulmonary vascular tone at baseline or during lobar hypoxia, but enhanced the diversion of blood flow and arterial blood oxygenation during lobar hypoxia. This enhanced HPV response probably reflects hemodynamic changes, such as decreased cardiac tension, due to sympathetic nerve activity blockade by TEA.

Analysis of Variance↗

Effects of hypertrichotic agents on follicular and nonfollicular cells in vitro.

Our previous studies revealed that topical minoxidil induced an increased rate of DNA synthesis in both dermal papilla and follicular germinal cells in early anagen and bulbar matrix as well as outer root sheath and perifollicular fibrocytic cells in mid and late anagen follicles in the bald scalp of the stump-tailed macaque. However, the epidermis and dermal fibrocytes showed no response. To determine the specific action of hypertrichotic agents on follicular cells, we examined the effects of two potent hypertrichotic agents, minoxidil and cyclosporin, on the DNA synthesis of cultured cells derived from either follicular cells (dermal papillar, perifollicular fibrocytic and outer root sheath cells) obtained from human and macaque scalps or nonfollicular cells (fibrocytes and epidermal keratinocytes) from human and macaque foreskin, palm and sole regions and the 3T3 cell line. Cultured subconfluent cells from the above follicular and nonfollicular specimens were incubated with either minoxidil (0.01-2 mM) or cyclosporin (0.01-100 mM) in medium (serum-free DMEM) for 48 h, then 3H-thymidine was added for the final 6 h. Minoxidil induced a significant increase in DNA synthesis in all follicular cells in a dose-specific manner (maximum rate at 0.5 mM for dermal papilla and perifollicular fibrocytic cells and 0.1 mM for outer root sheath cells). The perifollicular fibrocytic cells appeared to have a potentiality similar to that of the dermal papilla cells. Nonfollicular cells showed no response to minoxidil; 3T3 cells were rather suppressed. Cyclosporin appeared to have rather suppressive effects on both follicular and nonfollicular cells. These results suggest that minoxidil has a specific affinity to hair follicular cells and induced their cell proliferation. Although cyclosporin is known as a potent hypertrichotic agent, our studies on cultured follicular cells showed no direct proliferative effect. The hypertrichotic mechanism of cyclosporin appeared to be different from that of minoxidil.

3T3 Cells↗

Alveolar destruction in guinea pigs chronically exposed to diesel engine exhaust. A light- and electron-microscopic morphometry study.

Guinea pigs were exposed 16 h a day, 6 d a week, for 6, 12, 18, or 24 mo to filtered air or diesel-exhaust at low (NO2 = 0.22 +/- 0.03 ppm; SO2 = 0.60 +/- 0.19 ppm; particles = 0.21 +/- 0.07 mg/m3), medium (NO2 = 1.07 +/- 0.09; SO2 = 2.83 +/- 0.73; particles = 1.14 +/- 0.26) or high (NO2 = 2.88 +/- 0.29; SO2 = 6.49 +/- 1.75; particles = 2.94 +/- 0.69) concentrations, or at a medium concentration without particles (NO2 = 1.01 +/- 0.09; SO2 = 2.66 +/- 0.64; particles = 0.01 +/- 0.01). We quantitated the holes in the alveolar wall and alveolar size by using scanning electron microscopy (SEM). After 12 mo of exposure, the ratio of the area of alveolar holes to that of the alveolar wall, and the number of holes per alveolus, rose as the concentration and duration of exposure increased. There were no differences in alveolar size between the study groups. Animals exposed to the medium concentration of diesel exhaust without particles showed less of an increase in the development of holes than animals exposed to the same concentration of diesel exhaust with particles. These findings suggest that diesel exhaust causes alveolar destruction (alveolar holes) without an enlargement in alveolar size in a concentration- and duration-dependent manner. Particulate matter in diesel exhaust may play some role in the development of these lesions.

Animals↗

[Research and development of zonisamide, a new type of antiepileptic drug].

Zonisamide (1,2-benzisoxazole-3-methanesulfonamide, AD-810) is a broad spectrum antiepileptic drug which has been launched in Japan and South Korea. It lacks the ureide structure included in most of the existing antiepileptic drugs. Zonisamide was synthesized by the sulfonation and the successive amination of 1,2-benzisoxazole-3-acetic acid in a very poor yield. After several efforts to optimize the compound, zonisamide was selected based on the balance of the efficacy and safety. The yield was greatly improved by the development of new synthetic routes. Zonisamide suppressed maximal electroshock seizures in mice, rats, rabbits and dogs. Its therapeutic plasma concentration range between anticonvulsant and neurotoxic effects was much wider than that of the existing antiepileptic drugs. In electroencephalographic studies on animal models of epilepsy, zonisamide, like phenytoin and carbamazepine, restricted the spread or propagation of seizures and, like sodium valproate, it suppressed the epileptogenic focus activity. Zonisamide was effective in several kindling models. In clinical studies, zonisamide exerted the efficacy against partial seizures (simple, complex, secondarily generalized seizures) and some generalized seizures (tonic-clonic, tonic, atypical absence seizures) that were comparable to that of carbamazepine and sodium valproate, respectively. Zonisamide was also effective in monotherapy. The adverse effects related with zonisamide were mainly drowsiness, ataxia, loss of appetite and gastrointestinal symptoms. Serious adverse effects which may be life-threatening have not been reported.

Animals↗

Behavioral retardation in a macaque with autosomal trisomy and aging mother.

The social development of a female rhesus monkey (Macaca mulatta) was followed from the day of birth until her death, at age 32 months. The subject, born to an older mother, had an extra autosome (karyotype: 43, XX, +18), an affliction that came about spontaneously. MRI scans revealed that she was also hydrocephalic. Compared to 23 female monkeys growing up under identical conditions, the subject showed serious motor deficiencies, a dramatic delay in the development of social behavior, poorly established dominance relationships, and greater than usual dependency on mother and kin. The subject was well-integrated into the social group, however.

Animals↗

Beneficial effects of a novel anti-hypoxemic agent, TEI-7322, on bleomycin-induced experimental hypoxemia in rats.

Almitrine bismesylate is known to be an anti-hypoxemic agent that acts via the enhancement of hypoxic pulmonary vasoconstriction. However, screening for this class of compounds has been minimal, owing, in part, to a lack of convenient hypoxemic models in small animals. The present study was designed to establish a convenient model of hypoxemia induced by bleomycin and to evaluate anti-hypoxemic agents including a newly synthesized compound. TEI-7322, 2-allylamino-4-tert-butyl-amino-7-methyl-7H-pyrrolo[2,3- d]pyrimidine hydrochloride by using this model. Bleomycin was intratracheally instilled into rats. After 3 weeks, the arterial blood gas pressures were monitored in the animals in the conscious state. Then, prednisolone, doxapram, almitrine or TEI-7322 was administered to the bleomycin-treated rats to monitor changes in arterial blood gas pressures. Bleomycin-treated rats showed a decrease in the arterial blood O2 pressure (PaO2). The blood CO2 pressure (PaCO2) increased, along with an increase in the alveolar-arterial oxygen difference (AaDO2). These blood gas pressures in bleomycin-treated rats were not affected by treatment with prednisolone. Doxapram decreased the PaCO2 but did not change the PaO2. However, administration of almitrine or TEI-7322 significantly improved the PaO2 of bleomycin-treated rats with a decrease in the PaCO2. In conclusion, (1) bleomycin-induced lung injury causes hypoxemia in rats, probably resulting from ventilation-perfusion inequality; thus this model may be useful for evaluating anti-hypoxemic agents; and (2) TEI-7322, as well as almitrine, showed anti-hypoxemic effects in this model with different properties from those of doxapram, possibly due to improvement of ventilation-perfusion inequality, indicating that TEI-7322 may be a potent candidate for the treatment of hypoxemia.

Almitrine↗

Localization of Fas antigen mRNA induced in postischemic murine forebrain by in situ hybridization.

The expression of mRNA for the Fas antigen, a membrane-associated protein mediating apoptosis, was localized by in situ hybridization histochemistry in murine brains following 30 min of global cerebral ischemia. Six hours following the ischemia, many labeled cells were detected anew throughout the brain. The hybridization was seen in the small neural cells and in the cells along the walls of the ventricles and vessels, and became undetectable 24 h following the ischemia. These results suggest that the Fas antigen is expressed in the neuron, glia and periventricular cells of the post-ischemic brain.

Animals↗

Chronic psychosocial stress induces morphological alterations in hippocampal pyramidal neurons of the tree shrew.

The effect of sustained psychosocial stress on the morphology of hippocampal pyramidal neurons was analysed in male tree shrews after 14, 20, and 28 days of social confrontation. A variety of physiological changes such as constantly elevated levels of urinary cortisol and norepinephrine and reduced body weight, which are indicative of chronic stress were observed in the subordinate, but not in the dominant males. Light microscopic analysis of Nissl-stained hippocampal sections showed that the staining intensity of the nucleoplasm in the CA1 and CA3 pyramidal neurons was increased after prolonged psychosocial stress, indicating a change in the nuclear chromatin structure. These alterations were observed only in subordinate animals and increased in a time dependent manner in accordance with the length of the stress period. There was, however, neither a reduction in density nor a degeneration of pyramidal neurons in chronically stressed animals. Mechanisms which may possibly account for the observed alterations are discussed.

Age Factors↗

Lipidosis of the dorsal root ganglia in rats treated with an almitrine metabolite.

Toxic effects of a detriazinyl metabolite of almitrine (DTMA) were evaluated in rats and on cultured rat macrophages. In rats daily treated with DTMA for 16 weeks, spastic gaits with heel-lifting appeared, and lamellated and/or crystalloid bodies formed in sensory neurons, satellite cells, Schwann cells, and vascular endothelial cells of the dorsal root ganglia. The lysosomal lamellated bodies, which were not induced by almitrine, were produced also in cultured rat macrophages exposed to over 1 x 10(-5) M DTMA.

Administration, Oral↗