Jaundice and anaemia.
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Anemia, Hemolytic↗
Biomedical subjects
T Oshiro
Publications and source records attributed to T Oshiro.
A defect in a fatty acyl-CoA synthetase gene, lcf1+, results in a decrease in viability after entry into the stationary phase in fission yeast.
An intriguing mutant was isolated in Schizosaccharomyces pombe, which is defective in the maintenance of viability after entry into the stationary phase. In the logarithmic growth phase, the mutant cells grow at the same rate as the parental cells. Upon the onset of the stationary phase, however, the mutant cells lose viability very rapidly. It was found that this phenotype was due to a mutational lesion in the lcf1+ gene, which encodes a long-chain fatty acyl-CoA synthetase. The lcf1Deltamutant shows pleiotropic phenotypes, in that they are also sensitive to high temperature (37 degrees C) and to high salt concentrations (0.9 M KCl) in the medium. Based on the fact that Lcf1 is highly homologous to Faa1 and Faa4 of Saccharomyces cerevisiae, both of which have previously been suggested to play roles in the maintenance of endogenous acyl-CoA pools, the possible function of Lcf1 in S. pombe is discussed.
Coenzyme A Ligases↗
Immunolocalization of vacuolar-type H+-ATPase, cathepsin K, matrix metalloproteinase-9, and receptor activator of NFkappaB ligand in odontoclasts during physiological root resorption of human deciduous teeth.
To investigate the cellular mechanisms of physiological root resorption in human deciduous teeth, the authors examined the immunocytochemical localization of vacuolar-type H+-ATPase, a lysosomal cysteine proteinase, cathepsin K, matrix metalloproteinase-9 (MMP-9), and receptor activator of NFKB ligand (RANKL) in odontoclasts. H+-ATPase, cathepsin K, and MMP-9 are the most important enzymes for decalcification of apatite crystals and degradation of type-I collagen. In addition, RANKL is one of the key regulatory molecules in osteoclast formation and functions. Odontoclasts developed extensive ruffled borders and clear zones apposed to the resorbing root dentine surfaces. On immunoelectron microscopy, the expression of vacuolar-type H+-ATPase was detected along the limiting membranes of pale vacuoles and the ruffled border membranes of odontoclasts. Cathepsin K in odontoclasts was localized within pale vacuoles, lysosomes, the extracellular canals of ruffled borders, and the underlying resorbing dentine surfaces. MMP-9 localization in odontoclasts was similar to those of cathepsin K. RANKL was detected in both mononuclear stromal cells and odontoclasts located on resorbing dentine surfaces. These results suggest that (1) odontoclasts are directly involved in decalcification of apatite crystals by active extrusion of proton ions mediated by H+-ATPase and (2) extracellular degradation of dentine type-I collagen by both cathepsin K and MMP-9, and (3) odontoclast differentiation and activity are regulated, at least in part, by RANKL, possibly produced by mononuclear stromal cells and odontoclasts themselves in the resorbing tissues. Thus, the cellular mechanisms of physiological root resorption appear to be quite similar to those of osteoclastic bone resorption.
Carrier Proteins↗
Improved hepatic microcirculation by human soluble urinary thrombomodulin in the xeno-perfused porcine liver.
PURPOSE: Both the protein C/thrombomodulin system and the heparin/anti-thrombin III system are major physiological anticoagulant systems, which may also play a major role in preserving the hepatic microcirculation in xenogeneic liver transplantation. To compensate for the functional incompatibilities of the porcine thrombomodulin (TM)-cofactor activity beyond species for human thrombin, soluble human TM protein was tested in xenogeneic perfusion of the porcine liver. MATERIALS AND METHODS: The livers were harvested from adult female pigs and perfused through the portal vein (PV) and hepatic artery (HA) for 2 hr, with fresh human blood in group 1 (n=5), fresh porcine blood (10 units/ml) in group 2 (n=5), and fresh human blood with TM (50,000 units/1.5 l) in group 3 (n=5). The tissue PO2 level, tissue blood flow, PV and HA pressures were all continuously monitored. Circulating perfusate and liver tissue samples were periodically obtained for blood chemistry and histologic analyses. RESULTS: The activated protein C (aPC) level was significantly elevated in the TM-treated group 3 (47.5%+/-3.5% at preperfusion and 51%+/-2.8% after 120 min of perfusion) in comparison to group 1 (32.3%+/-7.2% and 35.3+/-12.0%). The hepatocyte enzyme release of aspartate aminotransferase (AST) was suppressed significantly more in group 3 (238.2+/-107 IU/l), than in group 1 (672.3+/-160 IU/l) at 2 hr after reperfusion. In group 3, the tissue PO2 levels and tissue blood flow also remained significantly higher throughout the perfusion. The platelet counts in the perfusate remained significantly higher in group 3 (37.1% to 74.3% of the preperfusion level) than in group 1 (4.4% to 14.7%), after 0 to 80 min of perfusion. According to the histologic findings, the degree of interlobular hemorrhaging and congestion decreased remarkably more in group 3 than in group 1. CONCLUSION: These findings thus indicated that soluble thrombomodulin protein extracted from human urine remarkably improved hepatic microcirculation in the xenoperfused porcine liver. The thrombomodulin/protein C system might, thus, play an important role in restoring the physiological anticoagulant system in the xenoperfused porcine liver.
Animals↗
G protein modulation of voltage-sensitive muscarinic receptor signalling in mouse pancreatic acinar cells.
Submaximal stimulation of mouse pancreatic acinar cells by acetylcholine (ACh) generates periodic Ca2+ responses sensitive to the membrane potential. Monitoring the muscarinic Ca2+ responses using patch-clamp whole-cell current recordings, we examined the mechanism of guanine nucleotide-binding protein (G protein)-receptor interaction in terms of the membrane potential. The lowest ACh concentration able to elicit consistent repetitive spikes was 50 nM, in the presence of which hyperpolarization increased and depolarization decreased the spike frequency. The saturating concentration was 10 microM, this induced a sustained response insensitive to voltage. Internal guanosine 5'-tri- and diphosphates (GTP, GDP) depressed and potentiated the voltage sensitivity, respectively, but not for the response to a saturating ACh concentration (10 microM). Internal guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS) abolished the voltage sensitivity. The results indicate that the ACh-induced Ca2+ response is sensitive to the membrane potential and that a close linkage exists between voltage sensitivity and the G protein association/dissociation cycle in the muscarinic receptor.
Acetylcholine↗
Decreased anterior cingulate myo-inositol/creatine spectroscopy resonance with lithium treatment in children with bipolar disorder.
This project was designed to compare differences in brain proton spectra between children and adolescents with bipolar disorder (BPD) and gender and age-matched normal controls, and to measure changes in myo-inositol levels following lithium therapy, utilizing in vivo proton magnetic resonance spectroscopy (1H MRS). A single voxel (2x2x2 cm3) was placed in brain anterior cingulate cortex for acquisition of the 1H spectra at baseline and after acute (7 days) lithium administration in 11 children (mean age 11.4 years) diagnosed with BPD, and in 11 normal controls. Acute lithium treatment was associated with a significant reduction in the myo-inositol/creatine ratio. This decrement was also significant in lithium-responders when analyzed separate from non-responders. Compared to normal controls, BPD subjects showed a trend towards a higher myo-inositol/creatine during the manic phase. These preliminary data provide evidence that a significant reduction in anterior cingulate myo-inositol magnetic resonance may occur after lithium treatment, especially among responders. Follow-up studies involving a larger sample may allow us to confirm whether changes in myo-inositol associated with acute lithium therapy persist in long-term clinical response of patients with and without lithium compliance.
Adolescent↗
Regulation of complex formation of POB1/epsin/adaptor protein complex 2 by mitotic phosphorylation.
RalBP1 and POB1, the downstream molecules of small GTP-binding protein Ral, are involved in receptor-mediated endocytosis together with Epsin and Eps15. The regulation of assembly of the complex of these proteins was examined. RalBP1, POB1, Epsin, and Eps15 formed a complex with alpha-adaptin of AP-2 in Chinese hamster ovary cells, but the formation was reduced in mitotic phase. RalBP1, POB1, Epsin, and Eps15 were all phosphorylated in mitotic phase. The phosphorylated forms of POB1 and Epsin were recognized by the antibody MPM2, which is known to detect mitotic phosphoproteins. POB1 and Epsin were phosphorylated by p34(cdc2) kinase in vitro. Their phosphorylation sites (Ser(411) of POB1 and Ser(357) of Epsin) were determined. Phosphorylated Epsin and Epsin(S357D) formed a complex with alpha-adaptin less efficiently than wild type Epsin. Although the EH domain of POB1 bound directly to Epsin, phosphorylation of Epsin inhibited the binding. Furthermore, Epsin(S357D) but not Epsin(S357A) lost the effect of Epsin on the insulin-dependent endocytosis. These results suggest that phosphorylation of Epsin in mitotic phase inhibits receptor-mediated endocytosis by disassembly of its complex with POB1 and alpha-adaptin.
Adaptor Proteins, Vesicular Transport↗
Two Tandemly Arrayed Transfer-RNA-Derived SINEs of the Medaka (Oryzias latipes).
Two tandemly arrayed short interspersed repetitive element (SINE) sequences were found in medaka (Oryzias latipes). These two SINE sequences, designated SINE1 and SINE2, were flanked by a 180-bp AT-rich region. Both appeared to be derived from transfer RNA. The former exhibited 80% sequence homology to human tRNA(Ala) and the latter exhibited 94% sequence homology to rat tRNA(Ser). SINE1 contained the retroviral U5 region, whereas SINE2 did not. This is the first sequence-level demonstration of the existence of neighboring SINEs in medaka.
Journal Article↗
Granular cell tumor of the rectum: a case report and review of the literature.
A 47-year-old Japanese woman with a 5-year history of alcoholism was admitted to the Ryukyu University Hospital for the treatment of the alcoholism. For evaluation of observed changes in her bowel habits, she underwent colonoscopy, which revealed seven small polyps spread throughout the entire large intestine. Six of the polyps were in the colon; one was an adenoma and five were hyperplastic polyps. The remaining polyp, in the rectum, was an 8-mm submucosal tumor. Pathological analysis of a biopsy of the lesion in the rectum indicated a possible diagnosis of adenocarcinoma. Endoscopic ultrasonography (EUS) demonstrated a submucosal hypoechoic nodule, involving the mucosa and the muscularis propria. Subsequently, the patient underwent a radical low anterior resection of rectum. The lesion was a submucosal tumor with ulceration. The tumor consisted of granular tumor cells which were positive for S-100 protein, neuron-specific enolase, and periodic acid schiff (PAS) stain, but negative for desmin and vimentin. Granular cell tumor is rare in the gastrointestinal tract. As a result, such tumors can be misinterpreted to indicate a possible malignancy on either a biopsy or EUS.
Biomarkers↗
Limitations of exogenous L-arginine in exerting a cytoprotective effect on hepatic ischemia/reperfusion injury.
To test whether or not the L-arginine/nitric oxide (NO) pathway induces a protective effect, we investigated the effect of exogenous L-arginine on hepatic ischemia/reperfusion (I/R) injury, using ex vivo perfusion of the isolated rat liver. The rat liver was removed and preserved in cold saline for 60 min, followed by 120 min of reperfusion with oxygenated perfusate at 37 degrees C. Either 600 mg/kg of L-arginine (groups 1 and 4), D-arginine (group 2), N(G)-nitro-L-arginine methyl ester (L-NAME) (group 3), or saline (group 5) were administered through the portal vein starting from 5 min before reperfusion to 5 min after reperfusion. In group 4, 600 mg/kg of L-NAME was preadministered at 10 min prior to the administration of L-arginine. The intrahepatic nitric oxide (NO) levels showed only a temporal elevation (227% +/- 70% of the pre-reperfusion levels at 5 min) after reperfusion in group 1. Pretreatment with L-NAME suppressed the elevation of the NO levels immediately after reperfusion in group 4. The lactate dehydrogenase release to the effluent perfusate significantly decreased and the histological findings showed that the sinusoidal damage observed after reperfusion was mitigated in group 1 more than in the other groups. These results thus suggest that exogenous L-arginine produced a relatively small amount of NO and therefore resulted in a slight decrease of hepatic I/R injury.
Animals↗
Adenovirus-mediated gene transfer of the triple human complement regulating proteins (DAF, CD59, MCP) in xenogeneic pig liver perfusion.
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Adenoviridae↗
Adenovirus-mediated gene transfer of DAF and CD59 in xenogeneic pig liver perfusion.
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Adenoviridae↗
Adenovirus-mediated triple gene transfer of human complement regulating proteins to the porcine endothelial cell.
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Adenoviridae↗
Characterization of platelet-activating factor-induced cytosolic calcium mobilization in human eosinophils.
BACKGROUND: Activated eosinophils play an important role in the pathogenesis of bronchial asthma and other allergic diseases, and platelet-activating factor (PAF) is a potent activator of eosinophils. OBJECTIVE: To characterize the cytosolic Ca2+ ([Ca2+]i) mobilization in human eosinophils in response to PAF. METHODS: [Ca2+]i responses to PAF were examined in human eosinophils using a microscopic fura-2 fluorescence-ratio imaging system. RESULTS: PAF caused a significant and dose-dependent increase in (Ca2+)i, which consisted of an initial rapid rise followed by a sustained elevation. This PAF-induced (Ca2+)i rise was inhibited by WEB 2086, a specific PAF receptor antagonist. The addition of 5 mM EGTA or 1 mM Ni2+ to a nominally Ca2+-free solution did not appreciably reduce the initial rise but significantly inhibited the sustained rise. The application of a protein kinase C inhibitor, Ro31-8220, augmented the sustained increase by PAF. Thapsigargin, a microsomal Ca2+ ATPase inhibitor, induced no appreciable change in a nominally Ca2+-free solution but induced a marked increase in (Ca2+)i when changed to a Ca2+-containing solution. CONCLUSIONS: The initial rapid rise and the following sustained rise in (Ca2+)i by PAF depends on Ca2+ release from the intracellular Ca2+ stores and Ca2+ influx, respectively, which are regulated by protein kinase C in human eosinophils. Furthermore, the so called Ca2+-capacitative entry is possibly involved in the Ca2+ influx from the extracellular solution in human eosinophils.
Calcium Signaling↗
Reduced expression of manganese superoxide dismutase mRNA may correlate with invasiveness in esophageal carcinoma.
Little is known about the expression and antioxidant function of manganese superoxide dismutase (Mn-SOD) in esophageal squamous cell carcinoma. To determine the significance of Mn-SOD in esophageal squamous cell carcinomas, Mn-SOD mRNA expression was examined in 45 esophageal squamous cell carcinomas and the corresponding normal mucosal tissues by reverse transcription-polymerase chain reaction. The tumor/normal (T/N) ratio of 45 patients with esophageal carcinoma was calculated, and the data were clinicopathologically analyzed. The T/N ratio of Mn-SOD mRNA expression was less than 0.5 in 11 (32.4%) of 34 esophageal carcinoma cases without any preoperative treatments, while none of 11 cases who underwent preoperative chemotherapy showed a T/N ratio of <0.5 (p < 0.05). There was an inverse correlation between the Mn-SOD expression level and the degree of venous invasion (p < 0.05) as well as lymphatic invasion (p < 0.05). Furthermore, poorly differentiated squamous cell carcinoma showed significantly lower Mn-SOD mRNA expression levels than well differentiated carcinoma (p < 0.05). Our results suggest that Mn-SOD mRNA was frequently reduced in esophageal carcinoma when compared to the normal mucosa and the reduced expression levels of Mn-SOD mRNA may lead to an accumulation of superoxide radicals in conjunction with the increased invasiveness of esophageal carcinoma.
Carcinoma, Squamous Cell↗
Migrating site of bleeding in a right colon demonstrating angio-dysplasia following a segmental resection of the colon. A unique variant of angiodysplasia.
BACKGROUND/AIM: A case of angiodysplasia of the right colon presenting with a migrating site of bleeding following a segmental resection of the colon in a 38-year-old Japanese is herein reported. METHODS: The case records of a patient with severe intestinal bleeding and multiple surgeries were reviewed, and then the histologic features were compared with the operative findings. The patient received many units of packed red blood cells and had also undergone three segmental colectomies and most recently a curative ileocolostomy. Despite an exhaustive evaluation, the bleeding sites could not be detected clinically. RESULTS: Ectatic, tortuous submucosal veins were presented in four sections of the colon (cecum, ascending colon and transverse colon, respectively) out of a total of 30 sections that were examined. These veins pierced the proper muscle layer of the colon, but did not traverse the muscularis mucosa. Our case of segmental microscopic angiodysplasia may represent a previously unreported unique variant, because the angiodysplastic lesions were present in the segmental colon and they developed bleeding from the distal remnant colon immediately after each segmental colectomy until an extended right hemicolectomy containing the oral part of the descending colon was done. In spite of the severe bleeding, the mucosa of the colon appeared to be essentially normal during a macroscopic inspection. CONCLUSION: Gastrointestinal bleeding from angiodysplasia is generally assumed to arise from macroscopically visible vascular lesions within the mucosa. However, angiodysplastic lesions are often unrecognizable and multiple in the gastrointestinal tract, and especially tend to affect both the cecum and ascending colon. When this disease process is recognized, a subtotal colectomy may thus be called for to control bleeding.
Adult↗
Suppression of maxi-K channel and membrane depolarization by synthetic polycations in single tracheal myocytes.
Polycationic proteins, e.g., major basic protein from eosinophils or cathepsin G from neutrophils, have been shown to increase nonspecific airway responsiveness. Along with several indirect manners of action, polycations were reported to contract smooth-muscle strips and to raise the cellular Ca(2+) concentration as a direct action on airway smooth muscle. However, the mechanistic basis for the direct behavior remains to be elucidated. To address this issue, we examined the effects of synthetic cationic polypeptides poly-L-arginine and poly-L-lysine on fresh single smooth-muscle cells from bovine trachea using a patch-clamp technique. Both of the polycations significantly depolarized the membrane from a baseline of about -40 to -20 mV in a dose-dependent manner. The polycations also suppressed whole-cell spontaneous transient outward currents as well as both the conductance (from a baseline of about 130 to 70 pS) and open-state probability (about 25% of control values) of large-conductance Ca(2+)-dependent K(+) channel (maxi-K channel) on excised outside-out patch membranes. The polycations were without effect on the whole-cell Ca(2+) currents induced by depolarizing voltage pulses. We concluded that the synthetic polycations had at least two sites of action; one is the delayed rectifier K(+) channel that is responsible for the membrane depolarization that increases Ca(2+) influx, and the other is the maxi-K channel the suppression of which inhibits muscle relaxation. These results may explain the direct contractile action and, therefore, one of the mechanisms underlying the airway hyperresponsiveness induced by various polycationic proteins.
Animals↗
A novel function of thyrotropin as a potentiator of electrolyte secretion from the tracheal gland.
Accumulating evidence suggests that thyrotropin (thyroid-stimulating hormone [TSH]) plays some roles in immunoregulation by an extrathyroidal action. Because airway submucosal glands are responsible for nonspecific and specific airway defense, we tested the effect of TSH on feline tracheal submucosal gland using a whole-cell patch-clamp technique, immunohistochemistry, and reverse transcription/polymerase chain reaction (RT-PCR). TSH potentiated neurotransmitter-induced ionic currents significantly in a dose-dependent manner. Acetylcholine (10(-)(8) M)- and norepinephrine (10(-)(7) M)-induced inward current (I(i)), which we previously showed to be a Cl(-) current, were increased to about 3-fold the pre-TSH control responses, respectively, by 2.0 ng/ml TSH; and to 6- and 23-fold the control values by 20.0 ng/ml TSH, respectively. TSH alone was without effect up to 20.0 ng/ml. Follicular stimulating hormone only slightly affected the I(i) (1. 5-fold the control). Analyses with immunohistochemistry and RT-PCR failed to identify TSH receptors on the glandular tissue. Maneuvers to raise the cellular adenosine 3',5'-cyclic monophosphate also failed to mimic the TSH-mediated potentiation. The TSH effect appeared to be mediated by a signaling pathway involving tyrosine kinase because its inhibitors (genistein and herbimycin A) abolished the augmentation completely, and interferon-gamma, a tyrosine kinase activator, imitated the TSH action on submucosal gland. Thus, TSH may be an important regulator of airway fluid secretion.
1-Methyl-3-isobutylxanthine↗