Biomedical subjects

H Ohno

Publications and source records attributed to H Ohno.

At least 325 records · Page 18Linked to original sources

PubMed1994

Oxidative stress induced by intermittent exposure at a simulated altitude of 4000 m decreases mitochondrial superoxide dismutase content in soleus muscle of rats.

The effects were examined of 6-month intermittent hypobaric (4000 m) exposure on the antioxidant enzyme systems in soleus and tibialis muscles of rats. At the end of the 6-month experimental exposure, the six rats in both the exposed group and the control group were sacrificed. Immunoreactive mitochondrial superoxide dismutase (Mn-SOD) contents were measured as well as the activities of antioxidant enzymes [Mn-SOD, cytosolic SOD (Cu,Zn-SOD), catalase (CAT), and glutathione peroxidase (GPX)]. Thiobarbituric acid-reactive substances (TBARS) were also determined as an indicator of lipid peroxidation. The high altitude exposure resulted in a marked increase in TBARS content in soleus muscle, suggesting increased levels of oxygen free radicals. Conversely, significant decreases in both Mn-SOD content and activity in soleus muscle were noted after exposure. Such trends were not noticed in tibialis muscle. On the other hand, no significant changes in Cu,Zn-SOD, CAT, or GPX were observed in either muscle. These results suggested that the increases in lipid peroxidation were most probably a result of decreased Mn-SOD function which was more depressed in oxidative than in glycolytic muscle.

Altitude↗

PubMed1994

Is insulin-like growth factor I involved in brown adipose tissue enlargement?

During cold exposure, the expression of insulin-like growth factor I (IGF-I) mRNA in rat brown adipose tissue (BAT) increased significantly with the increase in the BAT weight. In addition, the blood plasma from cold-acclimated (CA) rats enhanced the proliferation of brown adipocyte precursor cells in primary culture and the expression of IGF-I mRNA in them compared to those from warm-acclimated rats. The cell proliferation was considerably inhibited by anti-growth hormone (GH) antibody. These results suggest that IGF-I produced by brown adipocytes may play a role in BAT enlargement during cold acclimation. It is probable that some factors (including GH) concerned with the proliferation of brown adipocyte precursor cells are involved in the blood plasma from CA rats.

Adipose Tissue, Brown↗

PubMed1994

Non-Hodgkin's lymphomas with chromosomal translocations involving 3q27 band and immunoglobulin gene loci: report of two cases.

Two cases of non-Hodgkin's lymphoma (NHL) of B-cell origin with reciprocal chromosome translocations involving the 3q27 band and loci for the immunoglobulin genes are described. In case 1, [t(3;14)(q27;q32)], the 14q32 band for the immunoglobulin heavy chain gene was involved, and in case 2, [t(3;22)(q27;q11)], the reciprocal breakpoint was the 22q11 band where the immunoglobulin lambda light chain gene is located. Although the two patients shared some clinical features, the lymphomas varied in histologic phenotypes; in case 1, the lymphoma being a diffuse large cell subtype, whereas in case 2, the lymphoma being the high grade small noncleaved cell lymphoma. Thus, the consistent association of the 3q27 translocation with a specific subtype of NHL remains to be determined. Southern blot analysis of the lymphoma cells from the two patients showed rearrangements and deletions in immunoglobulin genes with features which cannot be explained by normal immunoglobulin-generating mechanisms and which suggest that the translocations involved these loci at the molecular level. Cloning of the breakpoint using DNA probes from the immunoglobulin genes would prove a novel oncogene at the 3q27 band.

Adult↗

PubMed1994

Prevention of ongoing lipid peroxidation by wound excision and superoxide dismutase treatment in the burned rat.

To determine if wound excision and superoxide dismutase (SOD) treatment prevent ongoing lipid peroxidation after burn injury, the plasma, kidney, and lung lipid peroxide (LPO) levels in 25% total body surface area (TBSA) burned rats was studied. The animals were given intraperitoneal bovine copper-, zinc-SOD (Cu/Zn-SOD) (50,000 U/kg dissolved in saline) or saline immediately after burns and were operated by wound debridement and allograft 2 hours after the burn. We measured LPO levels of 6-hour postburn plasma and tissues by the thiobarbituric acid (TBA) method, and measured the manganese SOD (Mn-SOD) by an enzyme-linked immunosorbent assay. Wound excision alone prevented the increase of plasma LPO levels but could not prevent the increase in tissues. The combination of wound excision and Cu/Zn-SOD treatment markedly inhibited the increase in both plasma and tissue LPO levels after the burn, but did not prevent the increase in Mn-SOD. Wound excision in conjunction with SOD-treatment might be therapeutic in the management of severe burns.

Analysis of Variance↗

PubMed1994

Two distinct pathways of specific killing revealed by perforin mutant cytotoxic T lymphocytes.

To study the contribution of putative perforin-independent mechanism in the antigen-specific target destruction by cytotoxic T lymphocytes CD8+ CTL lines were established from spleen cells of chimeric mice produced by injecting perforin (-/-) embryonic stem cells into blastocysts of RAG-2(-/-) mice. When tested on normal concanavalin A blasts, these perforin-deficient cytotoxic T lymphocyte lines were found to be capable of inducing antigen-specific target cell lysis accompanied by DNA degradation. In contrast, with target cells carrying a mutation in Fas molecule, perforin-independent cytotoxicity was not detectable. These data not only confirmed the primary role of perforin but simultaneously revealed a major contribution of a perforin-independent Fas-mediated pathway in antigen-specific cytolysis.

Animals↗

PubMed1994

Discordance between thermogenic activity and expression of uncoupling protein in brown adipose tissue of old rats.

To elucidate the reason why thermogenic ability is impaired with age, the relationship between thermogenic activity and gene expression of several proteins including uncoupling protein (UCP) in brown adipose tissue (BAT) was investigated in 24-month-old rats. Compared to young (3-month-old) rats, a significant decrease in BAT/body mass ratio and considerable changes of chemical components in BAT were observed in the old rats. This indicates a marked decrease in the thermogenic capacity in BAT of the old rats. Likewise, the thermogenic activity (which was assessed by guanosine 5'-diphosphate binding to BAT mitochondria) was greatly reduced in the mitochondria recovered from BAT of the old rats. However, the UCP content in the BAT mitochondria was similar in both groups. Conversely, the expression of UCP mRNA was greater in the old rats than in the young rats. These results suggest that the regulation on and after UCP translation may be concerned with impaired BAT thermogenic activity due to aging. Moreover, the mRNA levels of several other proteins including insulin-sensitive glucose transporter concerned in BAT thermogenesis changed with age, suggesting that the mRNA levels may be affected in order to compensate for the decline in the thermogenic activity in the old rats.

Adipose Tissue, Brown↗

PubMed1994

Different cytoplasmic structure of the CD3 zeta family dimer modulates the activation signal and function of T cells.

The TCR complex transduces the antigen recognition signal through common activation motifs present in both CD3 gamma delta epsilon chains and zeta dimers within the complex. We have investigated functional roles of the cytoplasmic domain in zeta and CD3 gamma delta epsilon for T cell activation in early and late responses by comparing the signaling capability of the TCR complexes containing mutant zeta lacking some or all motifs, or eta chain, another zeta family molecule. The results with the mutant zeta lacking all motifs indicated that CD3 gamma delta epsilon can transduce signals to cause early activation events and production of IL-2 upon antigen stimulation in the absence of zeta motifs. However, any one of the zeta motifs was required to respond to Thy-1 stimulation and this requirement cannot be replaced by other CD3 chains. Such zeta motif-dependent responses were also observed in tyrosine phosphorylation of a 90 kDa protein upon TCR stimulation. Furthermore, we found that the C-terminal unique region of the eta chain exhibits inhibitory function in phosphorylation and Ca2+ response upon TCR stimulation as well as IL-2 production upon Thy-1 stimulation. Collectively, the present analyses suggest that two types of signals are induced through the TCR-CD3 complex: (i) the common motif-dependent signals which are mediated equally through zeta dimers and CD3 gamma delta epsilon, and (ii) zeta specific motif-dependent signals. Differences in the cytoplasmic domain of zeta family molecules may modulate the cooperation of these two signals, resulting in alteration of T cell functions.

Animals↗

PubMed1994

Adaptation of Aspergillus niger to several antifungal agents.

Adaptation of Aspergillus niger to short-term stress induced by three antifungal agents [amphotericin B (AMPH), miconazole (MCZ), and ketoconazole (KCZ)] was observed and evaluated quantitatively using individual hyphae. Spores were inoculated onto a poly-L-lysine-coated glass plate making up the base of a culture vessel. Potato dextrose broth (PDB) was added and the vessel incubated for 24 h at 28 degrees C. The growth rate of an arbitrarily selected test hypha was measured automatically. Exposure to AMPH (0.075 micrograms ml-1) stopped the growth of the hypha. After washing with PDB, the same concentration of AMPH was applied again. The growth of the test hypha was not inhibited. This phenomenon was defined as adaptation to the short-term stress of AMPH. Similarly, adaptation was observed with MCZ (0.01 microgram ml-1) and KCZ (0.5 microgram ml-1). The time required for the test hypha to restart growth after washing with PDB depended upon the concentration of MCZ or KCZ, but not upon the concentration of AMPH.

Adaptation, Physiological↗

PubMed1994

Heterogeneity in B-cell neoplasms associated with rearrangement of the LAZ3 gene on chromosome band 3q27.

The LAZ3 gene has been identified on chromosome band 3q27, which is the breakpoint of reciprocal chromosome translocations observed in B-cell non-Hodgkin's lymphoma (NHL). Although the translocations affect various chromosome sites including the immunoglobulin gene loci, molecular studies have indicated that the breakages are clustered within a 10-kb-long major translocation cluster region (MTC) at band 3q27. In the current study, we have used a genomic probe from the MTC to study 51 Japanese patients having B-cell neoplasms with regard to rearrangement of LAZ3. The study detected rearrangement in 12 cases out of 51; the rearrangements occurred within a limited region close to the first exon of the LAZ3 gene. Eight cases out of 12 with rearrangement had diffuse large cell NHL and the immunoblastic variant, including one case transformed from a follicular lymphoma carrying the BCL2 rearrangement. However, the rearrangement was also identified in two NHL patients showing a follicular growth pattern, in one case with indolent chronic lymphocytic leukemia and in one case with high-grade small noncleaved cell lymphoma with a bulky abdominal mass. Cytogenetic analysis revealed t(3;14)(q27;q32) in 2 cases, t(3;22)(q27;q11) in 3, and a newly identified translocation t(3;6)(q21) in one case. LAZ3 expression was demonstrated in cells carrying the LAZ3 rearrangement, suggesting transcriptional deregulation of the gene. Our results are compatible with previous cytogenetic reports in which the 3q27 translocation was observed in 15-20% of NHL; however, patients with the LAZ3 rearrangements exhibited a wide range of clinico-pathologic characteristics. Thus, there is no clear consistent association of the 3q27 translocation with a specific subtype of B-cell neoplasm.

Adult↗

PubMed1994

Activation of phospholipase C-gamma 1 through transfected platelet-derived growth factor receptor enhances interleukin 2 production upon antigen stimulation in a T-cell line.

Phospholipase C-gamma 1 (PLC gamma 1) plays an important role in the signal transduction pathway by producing second messengers. However, the activation mechanism of PLC gamma 1 and the role of the phosphatidylinositol pathway for interleukin 2 (IL-2) production in T lymphocytes remain to be determined. To analyze the functional role of this pathway in T cells, we expressed an epidermal growth factor receptor (EGF) or platelet-derived growth factor (PDGF) receptor (EGF-R or PDGF-R), both of which are known to directly activate PLC gamma 1 in fibroblasts, into a murine T-cell hybridoma. Both receptors were expressed on the cell surface and caused tyrosine phosphorylation of multiple substrates, including the receptor itself, upon ligand binding. While EGF stimulation did not either cause phosphorylation of PLC gamma 1 or induce Ca2+ mobilization in the EGF-R transfectant in this system, PDGF treatment induced tyrosine phosphorylation of PLC gamma 1 and Ca2+ mobilization in the PDGF-R transfectant. Stimulation through PDGF-R enhanced IL-2 production upon antigen stimulation of the transfectants, although PDGF treatment alone did not induce IL-2 production. These results suggest that activation of the phosphatidylinositol pathway affects the downstream pathway to IL-2 production but is not sufficient to produce IL-2 and that cooperation with signals from tyrosine kinase cascades is required for IL-2 production.

Animals↗

PubMed1994

Atypical pemphigus with concomitant IgG and IgA anti-intercellular autoantibodies associated with monoclonal IgA gammopathy.

A case is reported of a 60-year-old woman with acantholytic vesiculopustular dermatosis and IgA-lambda monoclonal gammopathy. The histopathology of vesiculopustular lesions showed intraepidermal acantholytic and neutrophilic blisters. Direct immunofluorescence revealed intercellular (IC) IgD deposition with concurrent deposits of IgA and C3. Indirect immunofluorescence and immunoblotting studies revealed that the patient had circulating IgG and IgA anti-IC antibodies both of which recognized the 150-kD desmoglein that was pemphigus foliaceus antigen in a bovine desmosome preparation.

Autoantibodies↗

PubMed1994

Development of a sensitive two-site immunoradiometric assay for parathyroid hormone-related peptide: evidence for elevated levels in plasma from patients with adult T-cell leukemia/lymphoma and B-cell lymphoma.

We have developed a sensitive immunoradiometric assay for PTH-related peptide (PTHrP) using a monoclonal antibody against PTHrP(1-34) and a polyclonal antibody against PTHrP(50-83), with recombinant human PTHrP(1-87) as the standard. The detection limit of the immunoradiometric assay was 0.5 pmol/L, and plasma PTHrP(1-87) concentrations in 110 healthy subjects were 0.8 +/- 0.01 pmol/L, with the upper limit of the normal range being 1.1 pmol/L. Increased circulating PTHrP(1-87) concentrations were demonstrated in all 46 cancer patients with hypercalcemia, but not in patients with primary hyperparathyroidism, chronic renal failure, or hypoparathyroidism. Normalization of serum calcium levels after resection of tumors was shown to correlate well with that of plasma PTHrP(1-87) concentrations in 2 cancer patients. High circulating PTHrP(1-87) levels were also demonstrated in 12 out of 13 hypercalcemic patients with adult T-cell leukemia/lymphoma and in 7 out of 8 hypercalcemic patients with non-Hodgkin's lymphoma especially of B-cell type. These results suggest that PTHrP is a major humoral factor responsible for the hypercalcemia frequently associated with adult T-cell leukemia/lymphoma and also with B-cell lymphoma.

Adult↗

PubMed1994

[Studies on growth of brown adipose tissue by means of cell culture and angiogenesis in vitro techniques].

To elucidate the mechanism of brown adipose tissue (BAT) enlargement, we investigated the effects of norepinephrine (NE) and insulin on the in vitro growth of rat brown adipose cells (RBAC) and the capillary growth in angiogenesis in vitro using co-culture of bovine capillary endothelial cells (BCEC) and rat smooth muscle cells. In the primary cell culture, NE significantly enhanced the growth of RBAC in the range of 10(-9)-10(-5)M, whereas it did not stimulate the growth of BCEC. Insulin showed the same trend. Moreover, both NE and insulin appeared to increase the expression of mRNA for basic fibroblast growth factor (bFGF), which is a potent angiogenic factor, in RBAC. At 4 h after NE stimulation, the bFGF mRNA expression was considerably increased but it decreased markedly after 16 h. These results suggest that the bFGF mRNA expression in RBAC is quickly simulated by NE, wih resulting bFGF production. Actually, bFGF stimulated the RBAC growth up to about 170% of the control level. However, neither NE nor insulin stimulated the expression of the bFGF gene in BCEC. On the other hand, NE notably increased the capillary growth in vitro compared with insulin. It is thus possible that NE and insulin contribute to the growth of RBAC and endothelial cells partly through bFGF production by an autocrine mechanism, suggesting that both agonists play an important role not only in the thermogenic function of BAT but also in BAT enlargement.

Adipose Tissue, Brown↗

PubMed1994

Chronic exposure to simulated altitude does not increase angiogenic activity in skeletal muscle of rats.

In order to examine whether the hypoxia of high altitude increases angiogenic activity in skeletal muscle, six male Wistar rats were subjected to a simulated altitude of about 5,500 m (ambient pressure 380 mmHg) for 3 weeks, and the whole soleus, gastrocnemius, and extensor digitorum longus muscles were collected. As a result, any muscle extracts from high altitude rats did not significantly enhance the capillary growth in an in vitro angiogenesis model compared with those from sea-level rats. This appeared to confirm previous morphological studies that hypobaric-hypoxic environment did not cause the formation of new capillaries in skeletal muscles.

Altitude↗

PubMed1994

The effect of an SOD derivative (SM-SOD) administration in a burned rat model.

To determine whether superoxide radicals may influence the pathogenesis of burn injury, we investigated the effects of a long-acting, site-directed superoxide dismutase derivative (SM-SOD) on the rats subjected to burn shock. Anesthesized animals were injected intravenously with either 2 ml/kg of saline or SM-SOD (10 mg/kg; dissolved in saline). After 30 min they were subjected to full-thickness burns of about 40% of total body surface area. The 7-day survival rate was significantly higher in the SM-SOD-treated animals than in the untreated controls. Also, administration of SM-SOD markedly inhibited the increase in the levels of thiobarbituric acid reactive metabolites, such as lipid peroxides in the plasma, lung and kidney, and the decrease in plasma protein levels particularly at the early stage of burn injury. These findings suggested that superoxide radicals may play a critical role in the pathogenesis following thermal injury.

Animals↗

PubMed1994

[Increased serum alkaline phosphatase induced by DT-5061, an oral contraceptive, in rats].

DT-5061, a steroid oral contraceptive which contains norethisterone (NET) and ethinyl estradiol (EE) in a ratio of 100:7, was administered orally to rats for 14 days in order to investigate a possible origin of the increased serum alkaline phosphatase (ALP). Increased serum total ALP was noted in rats receiving DT-5061 at 5.35 mg/kg/day or EE at 0.35 mg/kg/day. Electrophoresis of serum ALP revealed that both liver and bone-type ALP isozymes were increased in the DT-5061 5.35 mg/kg and EE 0.35 mg/kg groups, and the ratio of increase in the liver-type was greater than that in the bone-type although the increase in concentration of the bone-type was greater as compared to the liver-type. ALP level in the liver was elevated together with an increase in liver weight, consistently with the increased serum liver-type isozyme. However, neither histological changes indicative of cholestasis nor increase in serum leucine aminopeptidase, bilirubin, GOT or GPT were seen. No changes were observed in bone ALP activity; hence inconsistent with the increased serum bone-type isozyme. From these results, it is considered that the increased serum ALP induced by this drug was due to the increased liver-type isozyme induced in the liver and to the increased bone-type isozyme, and among the ingredients of this oral contraceptive, EE was mainly involved in the increased serum ALP induced by this drug.

Administration, Oral↗

PubMed1994

[Effects of adrenalectomy on the increased serum alkaline phosphatase activity induced by DT-5061, an oral contraceptive, in rats].

DT-5061, a steroid oral contraceptive which contains norethisterone (NET) and ethinyl estradiol (EE) was administered orally to adrenalectomized rats for 3 days to investigate involvement of the adrenals in the increased serum alkaline phosphatase (ALP). In addition, corticosterone or aldosterone were administered to the adrenalectomized rats to examine their effects on serum ALP. Increases in serum total ALP, liver-type and bone-type ALP isozymes were observed in rats with intact adrenals following administration of DT-5061, but these responses were not noted in adrenalectomized rats. Increases in liver weight and ALP activity in the liver after administration of the drug were reduced but not abolished in the adrenalectomized rats. The adrenalectomized rats receiving corticosterone showed increases in serum total ALP, liver-type ALP isozyme and liver weight but did not exhibit any increase in bone-type ALP isozyme. On the other hand, aldosterone did not increase and even reduced serum ALP although ALP activity in the liver was increased in the adrenalectomized rats.

Adrenal Glands↗

PubMed1994

Responses of contractile properties in rat soleus to high-energy phosphates and/or unloading.

Responses of contractile properties of soleus to unloading and/or changes in high-energy phosphate contents were studied in rats. Reduction of high-energy phosphates, especially phosphocreatine, in ankle extensors was induced by feeding beta-guanidinopropionic acid (beta-GPA). The major finding in the study was that the fatigability and speed-related contractile properties responded to unloading and creatine supplementation in a similar manner. The high-energy phosphate contents tended to be elevated after 10-d supplementation of creatine and hindlimb suspension. The shift toward slow-type, mainly due to an increased one-half relaxation time, was seen in rats fed beta-GPA. Such a shift was reversed by feeding creatine or by hindlimb suspension; however, the suspension-induced shift of contractile properties toward fast-type was not prevented completely by beta-GPA feeding. Although the muscle fatigue resistance did not change by beta-GPA feeding alone, the decrease in fatigue resistance following suspension and creatine supply was less in the beta-GPA group. It is suggested that the levels of high-energy phosphates and tension production play important roles in the regulation of contractile properties of the soleus muscle.

Animals↗