Biomedical subjects
Publications and source records attributed to S Chiba.
We report two patients with biopsy-proven focal myositis, successfully treated with a peripheral arterial injection of low-dose prednisolone. Spin-echo T2-weighted magnetic resonance images helped to identify affected muscles and proved to be useful for monitoring treatment.
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BACKGROUND: The immune mechanism of gelatin allergy, especially the participation of TH1 and TH2 cells and their cytokine secretion, has not been investigated. OBJECTIVE: We investigated the characteristics of T lymphocytes from patients allergic to gelatin-containing vaccine by secondary in vitro stimulation of circulating mononuclear cells with gelatin. METHODS: We studied 8 children with a history of immediate-type reactions and 8 with nonimmediate-type reactions after inoculation of gelatin-containing vaccine. The expression of IFN-gamma (TH1 ), IL-2 (TH1 ), IL-4 (TH2 ), and IL-13 (TH2 ) mRNA was examined semiquantitatively by using a reverse transcriptase PCR. IgE antibody to bovine gelatin was measured with the fluorometric ELISA system, and gelatin-specific T-cell responses were detected by an in vitro lymphocyte proliferation assay. RESULTS: Patients with an immediate reaction all had gelatin-specific IgE antibody, whereas others did not. However, all patients exhibited positive T-lymphocyte responses specific to gelatin. Lymphocytes from subjects with nonimmediate-type reactions generally expressed very weak or sometimes no IFN-gamma, IL-2, or IL-13 genes and especially no IL-4 gene. On the other hand, the lymphocytes of subjects with immediate-type reactions significantly expressed not only IL-4 and IL-13 but also IFN-gamma and IL-2 mRNA. CONCLUSION: Our observations suggest that both gelatin-specific TH2 and TH1 responses are involved in the pathogenesis of the immediate reaction to gelatin. The gelatin-specific IL-4 and/or IL-13 responses consistently observed in patients with an immediate reaction may be associated with the production of gelatin-specific IgE antibody.
A clinical trial of the immunosuppressive drug deoxyspergualin (DSG) was conducted in five patients with various forms of proliferative glomerulonephritis (immunoglobulin A nephropathy in two patients, purpura nephritis in one patient, membranoproliferative glomerulonephritis in one patient, and rapidly progressive glomerulonephritis in one patient). DSG was intravenously administered at 0.25 or 0.5 mg/kg/d for 4 weeks. A marked decrease in proteinuria (to <50% of baseline) was observed in four patients, and the other patient showed a 38% reduction in proteinuria, but the proteinuria was exacerbated again after discontinuation of DSG in three patients during a 4-week follow-up period. Proinflammatory CD16(+) (FcgammaRIII) monocytes disappeared from the peripheral blood during the administration of DSG but reappeared after DSG treatment was discontinued. A significant decrease in urinary macrophage counts that was far more marked than the decrease in peripheral blood monocyte counts was observed after administration of DSG. Interestingly, we also observed that the CD16 marker on the CD14(+) macrophage population in the urine disappeared in response to DSG treatment. These findings suggest that DSG may have a unique effect of suppression of FcgammaRIII expression on monocytes and/or macrophages that may result in amelioration of activated macrophage-mediated glomerulonephritis.
By generating new junctional fragments from the recombinant Charcot-Marie-Tooth (CMT) 1A-REPs in CMT1A patients, a 3.2-kb recombination hot spot is observed in three quarters of CMT1A patients. By a polymerase chain reaction (PCR) method the authors analyzed eight patients CMT1A duplication, confirmed by Southern blot, to detect a recombination hot spot. Four patients had a novel 3.2-kb junctional fragment by PCR analysis. These four patients with a novel 3.2-kb junctional fragment had an abnormal 1789-bp fragment in addition to 1986-bp fragment after NsiI digestion (type 1). One patient who demonstrated no novel 3.2-kb junctional fragment had an abnormal 336-bp fragment in addition to 265 bp (type 2). Three patients with CMT1A duplication were not diagnosed as having CMT1A on the basis of PCR analysis. The PCR-based DNA test is valuable for screening to detect CMT1A duplication.
1. P2X-Purinoceptors and alpha1-adrenoceptors have previously been shown to involve in the double peaked vasoconstrictor responses to periarterial electrical nerve stimulation in the isolated and perfused canine splenic artery. The present study made an attempt to investigate effects of prolonged cold storage (7 days at 4 degrees C) on vasoconstrictor responses to periarterial electrical nerve stimulation, tyramine, noradrenaline and adenosine 5'-triphosphate (ATP) in the isolated canine splenic artery. 2. The periarterial nerve stimulation (1-10 Hz) readily causes a double peaked vasoconstriction in the non-stored preparations. After cold stored for 7 days, the double peaked vasoconstriction was still recognized, although the response became significantly smaller. The first phase was decreased relatively greater than the second phase by the cold storage. 3. In the cold stored preparations, the dose-response curve for tyramine was shifted to the right in a parallel manner. Prazosin almost completely inhibited tyramine-induced vasoconstriction but alpha,beta-methylene ATP failed to influence the response to tyramine. 4. The vasoconstrictor responses to noradrenaline and ATP were not significantly modified by the prolonged cold storage. 5. From these results, it is concluded that the functions of sympathetic co-transmission of purinergic components might be influenced more than that of adrenergic components in the cold storage canine splenic artery.
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We describe a patient who developed Aspergillus tracheobronchitis after BMT. She complained of progressive dyspnea on day +165 and her respiratory function deteriorated rapidly. Although neither early chest X-rays nor CT scans were negative, bronchoscopy revealed formation of a pseudomembrane around the bronchial walls. Based upon pathological and microbiological examinations, she was diagnosed as having invasive Aspergillus tracheobronchitis. Retrospectively analyzed, the Aspergillus circulating antigen detection tests became positive before clinical symptoms developed, and may be beneficial for early diagnosis of Aspergillus tracheobronchitis. This form of aspergillosis should be regarded as one of the serious complications after BMT.
BACKGROUND: The cytokine tumour necrosis factor (TNF) alpha has been reported to induce metabolic abnormalities such as anorexia and thermogenesis. To investigate functional modulators of uncoupling protein-2 (UCP2) gene expression, we examined the effects of TNF-alpha on UCP2 mRNA expression in rats. METHODS: Mature male Wistar King A (WKA) rats at 10-11 weeks of age were treated with recombinant human TNF-alpha at a dose of 0.6 nmol 100 g-1 body weight by intraperitoneal administration. RESULTS: TNF-alpha treatment induced an increase in UCP2 mRNA expression in broadly distributed tissues including brown adipose tissue (BAT), white adipose tissue (WAT) and skeletal muscle, and an elevation of ob gene mRNA expression in WAT. After the TNF-alpha treatment, an increase in plasma leptin concentration occurred in an ob gene-dependent manner, accompanied by an anorectic effect. CONCLUSION: The present results provide evidence for a new regulatory loop involving TNF-alpha and UCP2, and add novel insights into the regulatory mechanisms of energy homeostasis.
1. Periarterial nerve electrical stimulation caused a double peaked vasoconstriction in isolated perfused canine splenic arterial preparations. At low frequencies (1-3 Hz), the 1st peak responses were significantly inhibited by alpha,beta-methylene ATP. On the other hand, at high frequencies (8-10 Hz), the responses were not completely inhibited by alpha,beta-methylene ATP but the remaining response was abolished by an additional treatment of prazosin. 2. Concerning the 2nd peak responses, at low frequencies (1-3 Hz), the response was mostly suppressed by alpha,beta-methylene ATP, but at high frequencies (6-10 Hz), the response was not significantly modified by it, although the remaining responses were completely blocked by prazosin. Thus, at high frequencies an adrenergic and purinergic interaction may exist presynaptically, to prevent the inhibition by alpha,beta-methylene ATP. 3. At 1 Hz, rauwolscine, an alpha2-adrenoceptor antagonist, caused a potentiation of electrical stimulation-induced responses (both 1st and 2nd peaked responses) which were inhibited by prazosin, and the remaining ones were abolished by alpha,beta-methylene ATP. On the other hand, at 10 Hz, rauwolscine did not cause any potentiation of the double peaked responses. 4. The biphasic responses at 1 Hz were strongly inhibited by exogenously applied ATP, and its inhibition was reversed in part by a P1 receptor antagonist 8-phenyltheophylline (8-PT). On the other hand, the biphasic vasoconstrictions at 10 Hz were only slightly depressed by ATP, and a subsequent administration of 8-PT produced a partial recovery of the 1st phase response but not that of the 2nd one. 5. From these results, it is concluded that (1) at low frequencies the double peaked responses are mostly mediated via P2X receptor, presynaptic P1 receptors may also modulate the release of ATP, and presynaptic alpha2-adrenergic mechanism may tonically participate in the release of noradrenaline (2) at high frequencies the responses are mostly mediated via alpha1-adrenoceptors and presynaptic P2 receptors may exert its action to inhibit the release of noradrenaline from adrenergic nerve terminals.
1. The vascular response of isolated, perfused canine and simian femoral arteries, which distribute blood to deep skeletal muscles, were investigated. 2. The vascular responses to histamine, 2-pyridylethylamine (2-PEA), dimaprit and alpha-methylhistamine were pharmacologically analyzed in canine and simian vessels, using diphenhydramine (DPH, a histamine H1 receptor antagonist), cimetidine (a histamine H2 antagonist) and saponin which readily removed the endothelium. 3. In canine arteries, alpha-methylhistamine showed no vascular response, but in simian preparations, it caused a slight vasoconstriction. 4. In canine arteries, histamine and 2-PEA consistently induced a vasoconstriction in preconstricted and non-preconstricted preparations. However, in simian arteries histamine usually produced a vasodilatation at small doses (less than 10(-7) mol) and a vasoconstriction at large doses in preconstricted preparations. 5. Vasoconstrictor responses to histamine and 2-PEA were significantly inhibited by DPH in both species. In simian vessels, histamine- and dimaprit-induced vasodilatations were significantly inhibited by cimetidine. 6. After removal of the endothelium by intraluminal treatment with saponin in canine femoral arteries, the vascular responses to histamine, 2-PEA and dimaprit were not significantly affected. On the other hand, in simian femoral arteries, the vasodilatation responses to histamine and 2-PEA were significantly depressed by the removal of endothelium. 7. It is concluded that (1) in both simian and canine femoral arterial branches, there are abundant histamine H1 and H2 receptors (2) in simian but not in canine arteries, there exist histamine H3 receptors, although their role is not clear (3) histamine induces a vasoconstriction mediated via histamine H1 receptors and a vasodilatation via H2 receptors which exist in vascular smooth muscle, and (4) in simian but not in canine arteries, there are endothelium-dependent vasodilatation mechanisms.
1. In the present study, we investigated the effects of progressive inhibition of neuronal sodium channels by increasing concentrations of tetrodotoxin (TTX; 1-30 nmol/L) on the double-peaked vasoconstrictor responses to electrical periarterial nerve stimulation in the canine isolated and perfused splenic artery. 2. Double-peaked vasoconstrictions (biphasic vasoconstrictor responses) were consistently observed in following electrical stimulation with 30 s trains of pulses at 1-10 Hz. At low frequencies of stimulation (1-3 Hz), a submaximal concentration of 3 nmol/L TTX had no effect on the first phase of the contractile response, but almost completely inhibited the second-phase response. At high frequencies (6-10 Hz), the two vasoconstrictor phases were almost equally inhibited by 50% by 3 nmol/L TTX. A three-fold increase in the concentration of TTX used (10 nmol/L) abolished the second-phase vasoconstriction at all stimulation frequencies tested, whereas this concentration of TTX failed to block the first-phase response. Further increasing the concentration of TTX to 30 nmol/L completely blocked the remaining first-phase response. 3. Treatment with 0.1 mumol/L prazosin did not modify the first-phase response to any of the stimulation frequencies in the presence of 3 nmol/L TTX. Moreover, 0.1 mumol/L prazosin had no affect on the second-phase response at low frequencies (1-3 Hz), while at high frequencies (6-10 Hz) it slightly, but significantly inhibited the second-phase response. The vasoconstrictor responses that persisted after 3 nmol/L TTX and 0.1 mumol/L prazosin were completely suppressed by subsequent application of 1 mumol/L alpha, beta-methylene ATP at all stimulation frequencies (1-10 Hz). 4. In conclusion, progressive inhibition of sodium channels by increasing the concentration of TTX may exert a more preferential inhibition on adrenergic rather than purinergic components, suggesting that TTX-sensitive sodium channels may have a more important role in determining the adrenergic rather than purinergic transmission of sympathetic nerves.
Hybridoma cell lines were prepared from spleen cells of mouse immunized with mitotic HeLa cells. A monoclonal antibody (mH1), which intensively reacted with cleavage furrows of dividing HeLa cells in immunofluorescence, was obtained. In interphase, this antibody diffusely stained whole HeLa cells. Immunoelectron microscopy showed that mH1 antigens were localized at microvillus projections at the surface of dividing HeLa cells, but definite localization of that antigen was not observed in interphasic cells. Immunoblot analysis showed that mH1 is reactive to 42-kDa and 130-kDa components. Further, the 42-kDa component was identified as a gamma-actin homolog by N-terminal amino acid sequence analysis.
Ooplasmic segregation in ascidian eggs consists of two phases of cytoplasmic movement, the first phase is mediated by the microfilament system and the second is mediated by the microtubule system. Recently, two novel proteins, p58 and myoplasmin-C1, which are localized to the myoplasm, were suggested to have important roles in muscle differentiation. In order to analyze the molecular mechanisms underlying ooplasmic segregation, the interactions between actin, tubulin, p58 and myoplasmin-C1 were examined. During the first segregation, microtubule meshwork in the unfertilized egg disappeared. At the second segregation, a novel structure of the microtubules that extended from the sperm aster and localized in the cortical region of the myoplasm was found. Moreover, uniform distribution of the cortical actin filament was observed at the second segregation. During the course of myoplasm rearrangement, p58 and myoplasmin-C1 are colocalized and can form a molecular complex in vitro. This complex of p58 and myoplasmin-C1 is a good candidate for a cytoskeletal component of the myoplasm, and is likely to be involved in the correct distribution of cytoplasmic determinants.
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BACKGROUND: Valproic acid (2-propyl-N-pentanoic acid, VPA) causes severe hepatic dysfunction, similar to Reye's syndrome, in a small number of patients. An enhanced excretion of dicarboxylic acids by patients indicates an interference with mitochondrial beta-oxidation. We investigated the expression of various acyl-coenzyme A (acyl-CoA) dehydrogenases (ACD), which catalyze the first step of beta-oxidation in VPA-treated rats. METHODS: The control group received normal saline and the experimental group received VPA (500 mg/kg per day) by intraperitoneal injections for 7 days. Various clinical chemistry parameters in rat blood and free and total carnitine levels in plasma and tissue were determined. Mitochondria were isolated from rat liver and heart and the relative amount of each ACD protein was determined by immunoblot analysis. Total RNA was prepared from various tissues and the mRNA levels for various ACD were measured by slot-blot hybridization analysis using respective cDNA probes. RESULTS: Administration of VPA to rats caused various metabolic effects including hypoglycemia, hyperammonemia and decreased beta-hydroxybutyrate concentration. Free carnitine levels in plasma and heart were also decreased. Enzyme activities of various acyl-CoA dehydrogenases, which are involved in fatty acid oxidation, decreased moderately in heart (57-79%), and slightly in liver (78-95%). The most prominent effects were observed in mRNA levels involved in fatty acid oxidation (short-, medium- and long-chain acyl-CoA dehydrogenase). Each mRNA increased in the liver, kidney, skeletal muscle and heart to varying degrees when rats were fed ad libitum. The increase of short- and medium- chain acyl-CoA dehydrogenase mRNA in the heart were particularly large. However, 3 day starvation strongly inhibited expression of ACD in VPA-treated rats. There was an apparent decrease in the amount of ACD mRNA and proteins in VPA-treated liver. CONCLUSIONS: Valproic acid causes enhanced expression of fatty ACD mRNA, especially in the heart, by a feedback mechanism related to inhibition of beta-oxidation in rats fed ad libitum. However, it impairs the expression of ACD in the liver when there is a drastic change in nutritional state.
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Natural measles infection usually confers life-long immunity which is transferred from mothers to their offspring, protecting them from natural measles until the age of about 12 months. Recently, however, natural measles has been observed with increased frequency in infants under the age of 12 months. Natural measles outbreaks in the city of Sapporo have been suppressed by widely applied measles vaccination. Passive measles immunity in 160 neonates (cord blood), born during the last 17 y in Sapporo, Japan was determined by a neutralization (NT) antibody test. The mothers of these infants had had natural measles infection during childhood. Geometric mean titres (GMTs) of cord blood NT antibodies gradually decreased after 1989 and the GMTs of the most recently born infants were significantly lower than those of infants born in the first few years of the study. These observations suggest that even in mothers who experienced natural measles in childhood, recurrent exposure to natural measles is necessary in order to maintain adequate antibody levels for effective passive immunity of their infants.