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Biomedical subjects

H Uchida

Publications and source records attributed to H Uchida.

At least 253 records · Page 14Linked to original sources

Polymorphism of human minor histocompatibility antigens: T cell recognition of human minor histocompatibility peptides presented by HLA-B35 subtype molecules.

To investigate the polymorphism of human minor histocompatibility (mH) antigens, PBLs from 23 Japanese individuals and 25 German individuals with HLA-B35 were studied by using four human mH antigen-specific, HLA-B35-restricted CTL clones. The CTL clones killed PHA-stimulated PBLs from all 23 Japanese individuals. On the other hand, they killed the PHA-stimulated PBLs from 19 of 25 German individuals and partially killed the PHA-stimulated PBLs from three German individuals (CTL weakly sensitive cell line); those from another three individuals (CTL-resistant cell line) were not killed by the CTL clones. All of three CTL weakly sensitive cell lines carry HLA-B*3503 molecules, whereas the three CTL-resistant cell lines carry HLA-B*3502, B*3507, and B*3508 molecules. The cytotoxicity of the CTL clones for three CTL weakly sensitive cell lines was enhanced by stimulation of human mH peptides isolated from HLA-B*3501 molecules purified from C1R-B*3501 cells. Small amounts of human mH peptides were isolated from B*3503 molecules purified from these three CTL weakly sensitive cell lines. Taken together, these results indicate that weak recognition by the CTL clones of three CTL weakly sensitive cell line results from a small amount of the human mH peptides presented by B*3503 molecules. The CTL-resistant cell line carrying B*3507 loaded with the human mH peptides was killed by four CTL clones, whereas the cell lines carrying B*3502 or B*3508 loaded with the peptides were not. The human mH peptides were not isolated from B*3507 molecules purified from the cell lines expressing this subtype, whereas small amounts of the human mH peptides were isolated from B*3502 and B*3508 molecules purified from the cell lines expressing the subtypes. These results indicate that failure of the CTL recognition of the cell line carrying B*3507 is due to a lack of human mH antigens in this cell line. The failure of the CTL recognition of the cell lines carrying B*3502 and B*3508 is not explained by only the amount of the human mH peptides binding to these B35 subtype molecules because the amount of the human mH peptides eluted from B*3502 and B*3508 molecules purified from the cell lines carrying these B35 subtypes is almost the same as that eluted from B*3503 molecules purified from the cell lines carrying B*3503.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗

Regulation of granulocyte-macrophage colony-stimulating factor and interleukin 3 expression.

Granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin 3 (IL-3) are multilineage acting hematopoietic growth factors which have overlapping but distinct biological properties. Cellular sources of IL-3 are confined to activated T cells, natural killer (NK) cells, mast cells and possibly megakaryocytes, while these cells and activated macrophages, fibroblasts and endothelial cells are important sources of GM-CSF. In vitro studies have implicated both cytokines in the autocrine growth of human myeloid or murine mast cell leukemias. The human GM-CSF and IL-3 genes map to the long arm of chromosome 5, show similar genomic structures, and share several conserved elements in their 5' and 3' flanking regions. The promoters of these genes contain a variety of positive and negative regulatory regions, and the level of expression of these genes is controlled by both transcriptional and post-transcriptional mechanisms.

Base Sequence↗

Esophageal transection using a biofragmentable anastomosis ring in dogs.

Since the first publication on the new anastomosis technique using a biofragmentable anastomosis ring (BAR) by Hardy in 1985, various studies have been performed to investigate the superiority of this type of anastomosis, and it has since been reported that the BAR was safely used not only in large and small bowel anastomosis, but in cholecystojejunal and gastrojejunal anastomosis as well. In this study, the feasibility of the BAR for esophageal transection was investigated. Seven dogs were operated on, and one died of intraabdominal bleeding on the operative day while another died of leakage at the site of gastrotomy on the 3rd postoperative day. These deaths were all considered to be due to simple technical errors not directly related to the use of the BAR. The postoperative recovery of the other five dogs was uneventful, and the ring eventually disintegrated into several small fragments that passed out of the body in the faces between the 14th and 21st postoperative days. The dogs were killed on the 28th postoperative day, and both gross and histological examinations, revealed that the transection had been successful. Neither leakage nor significant stenosis at the site of transection was found. Our results suggested that the BAR could be used for esophageal transection and is thus recommended as an easy-to-learn, time-saving, and safe technique for esophageal operations.

Anastomosis, Surgical↗

Effect of anti-ICAM-1 and anti-LFA-1 antibodies on rat liver transplantation.

The effect of the anti-cell adhesion molecule antibodies, anti-ICAM-1 (1A29) and anti-LFA-1 (WT1), on rat liver transplantation was investigated. Livers from ACI rats were transplanted into Lewis rats by Kamada's method and during the recipient operation 1A29 1 mg/kg, and WT1 1 mg/kg were administered intravenously to one group of rats (treated group). The survival time of the treated group was significantly longer than that of the untreated group, but permanent unresponsiveness could not be induced. Postmortem examination revealed little histological evidence of acute rejection in treated rats, in which the main cause of death was thought to be chronic rejection.

Animals↗

Successful resection of a large hepatoblastoma in a young adult: report of a case.

Hepatoblastoma (HB) rarely occurs in adults, and very few cases of successful resection have been documented. We report herein the unusual case of a 22-year-old, otherwise healthy woman with no history of liver disease who presented with upper abdominal pain and hepatomegaly. Tests for hepatitis B virus (HBV) and hepatitis C virus (HCV) were negative, but the AFP was mildly elevated at 77 ng/ml, the normal being < 20. There was no evidence of liver cirrhosis on either the laboratory or histologic examinations. A well-demarcated solid mass of 14 cm in diameter, which was lobulated and partly necrotic, was detected in the liver by computed tomography (CT). The lesion was echogenic on ultrasound, slightly hypodense on CT, and mildly hypervascular on arteriogram. The entire tumor was resected by extensive hepatectomy preserving only the lateral segment and part of the posterior segment of the liver. Histologically, the neoplasm was diagnosed as a pure epithelial HB of the fetal type. Following the operation, the patient has been well and free of recurrence for 38 months, maintaining low alpha-fetoprotein (AFP) levels at around 5 ng/ml. To our knowledge, this is the longest reported survival of an adult following surgical resection of an epithelial HB.

Adult↗

Low-dose halothane produces airway dilatation but does not alter parenchymal mechanics in the normal canine lung.

The purpose of this study was to examine whether halothane reduces the contractile tone of the normal lung and to distinguish the effects of halothane on airways from those on lung tissue. We also tested whether a mathematical model was capable of quantitatively describing the mechanical changes in the lung produced by halothane. We measured lung impedence (ZL(omega) a complex function of real (lung resistance) and imaginary (reactance) parts) at low frequencies in dogs using a forced volume oscillation technique before and during 1 MAC halothane anaesthesia. Halothane produced small changes in ZL(omega). The lung resistance tended to decrease during halothane anaesthesia whereas the lung reactance did not show change. Using an alveolar capsule technique to separate the airways from the lung tissue components, these lung mechanical changes were induced mainly by alterations in lung tissue and not in the airways. Our mathematical model featured a single airway leading to an alveolar region surrounded by a viscoelastic lung tissue. In the model analysis, estimates of airway resistance and inertance decreased by the administration of halothane. In contrast, estimates of lung tissue elastance and resistance did not change during halothane anaesthesia. These modeling results were consistent with those obtained by direct alveolar pressure measurements. Our results suggest that a low concentration of halothane dilates the airways but does not alter the parenchymal mechanics in the normal lung, and that the model provides a quantitative tool to assess lung mechanics precisely, if respiratory signals are measured only at the true airway opening.

Airway Resistance↗

Antenatal diagnosis of biliary atresia (type I cyst) at 19 weeks' gestation: differential diagnosis and etiologic implications.

At 19 weeks' gestation, two cystic structures were first identified in the abdomen of a fetus. A repeat ultrasonography at 34 weeks confirmed a definite cyst communicating with the liver. The baby was born at 39 weeks, and serum direct bilirubin started to rise to 4.1 mg/dL. An operative cholangiogram at 23 days of life showed a cystically dilated choledochus with distal atresia and a relatively smooth yet hypoplastic intrahepatic biliary tree. Complete obliteration of the cystic duct was also noted. After excision of the cystic common bile duct, hepatico-jejunal anastomosis was performed, and the patient did well for 8 months postoperatively. Liver biopsy showed proliferation of the bile ductules, but no interlobular bile ducts were observed in any portal triad. A diagnosis of biliary atresia was established. Including the present case, five cases of antenatally diagnosed biliary atresia have been reported. All of them had type I cyst, and antenatal diagnosis was made at 19 to 32 weeks' gestation. Differential diagnosis between biliary atresia of type I cyst and choledochal cyst with complete distal obstruction has been a matter of discussion, and recognition of the entity of antenatally diagnosed biliary atresia is of significant importance from an etiological point of view.

Adult↗

Stability of microcystins from cyanobacteria--II. Effect of UV light on decomposition and isomerization.

Microcystins are very potent hepatotoxins and strong liver tumor promoters produced by cyanobacteria, and their occurrence has been reported all over the world. They could threaten human health when toxic Microcystis occurs in water supply reservoirs. In this study, we examined the stability of microcystins during photolysis with UV light. The toxins were easily decomposed by UV light at wavelengths around the absorption maxima of the toxins and the decomposition depended on the intensity of the light. The half-life of microcystin LR by 147 microW/cm2 UV irradiation was 10 min, and the toxin was completely decomposed by 2550 microW/cm2 UV after 10 min. When the toxins were irradiated with weaker UV light, isomerization was also observed by a different mechanism from that during photolysis by sunlight and pigment, and several products including three geometrical isomers of the conjugated diene of Adda were detected. Microcystin RR showed almost the same behavior as that of microcystin LR under the same conditions. Since no noxious products were formed in the present study, a water treatment including UV irradiation is very possible for removing microcystins from raw water.

Chromatography, High Pressure Liquid↗

Pharmacological profile of (-)HT-90B, a novel 5-HT1A receptor agonist/5-HT2 receptor antagonist.

1. HT-90B ((-)-N-([2-(8-methyl-l, 4-benzodioxane-2-ylmethyl)amino]ethyl) tricyclo[3,3,1,1(3.7)] decane-1-carboxamide) had high affinities for the 5-HT1A (Ki = 0.18 nM) and 5-HT2 (Ki = 9.2 nM) receptors. 2. HT-90B inhibited forskolin activated adenylate cyclase in rat hippocampal membranes as a 5-HT1A full agonist (IC50 = 2 nM), and the potency of the drug was higher than that of 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), a standard 5-HT1A agonist. 3. In the serotonin syndrome test, HT-90B behaved as a weak partial 5-HT1A agonist in reserpinized rats. 4. 5-HT2 receptor-mediated potentiation of rabbit platelet aggregation by serotonin (5-HT) was reduced by HT-90B (IC50 = 1.73 microM). 5. Head twitch response induced by 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), a 5-HT2 agonist, was inhibited by HT-90B in mice. 6. It is concluded that HT-90B has potent 5-HT1A receptor agonist as well as 5-HT2 receptor antagonist properties in vitro and in vivo.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Effect of propofol on spinal dorsal horn neurons. Comparison with lack of ketamine effects.

BACKGROUND: Pentobarbital reduces low-threshold receptive field (RF) size and enhances responses of some spinal dorsal horn neurons to noxious stimulation in cats. To better understand the effects of general anesthetics on spinal sensory processing, this study was designed to determine if intravenous propofol and ketamine have similar effects. METHODS: Spinal dorsal horn neuronal responses to RF stimulation were observed in physiologically intact, awake, drug-free cats. After baseline observations were made, the effects of propofol (7.5 or 10 mg/kg intravenous) or ketamine (10 mg/kg intravenous) on those neuronal responses were observed. RESULTS: Propofol is capable of producing a profound reduction in low-threshold RF size. Propofol also depressed neuronal responses to non-noxious and noxious RF stimulation in many of the neurons tested. Ketamine was not observed to produce any change in either RF size or neuronal response to non-noxious RF stimulation. CONCLUSIONS: General anesthetics that interact with gamma aminobutyric acid receptors may significantly depress low-threshold sensory information within the spinal dorsal horn. This may contribute to anesthetic-induced loss of sensation. Lack of a ketamine effect suggests an absence of n-methyl-d-aspartate receptor involvement in spinal dorsal horn processing of low threshold sensory information.

Action Potentials↗

Pharmacologic treatment of intimal hyperplasia after metallic stent placement in the peripheral arteries. An experimental study.

RATIONALE AND OBJECTIVES: To evaluate the efficacy of oral administration of cilostazol, an antithrombotic agent, for the prevention of thrombotic occlusion and intimal hyperplasia after stenting. METHODS: Single-bodied Z-stents were placed in the iliac arteries of 23 dogs. Before stenting, an embolizing coil was introduced into the right femoral artery to reduce blood flow in the right iliac artery. Eleven dogs were given cilostazol orally, and the other 12 were unmedicated as a control group. The dogs were killed at 4, 13, and 24 weeks. RESULTS: Intraluminal narrowing due to thrombus was observed in 25% of dogs in the control group but in none of the dogs in the cilostazol group. The thickness of the neointima was significantly thinner in the cilostazol group than in the control group at 24 weeks on the noncoiled side (P < 0.05), and at 4 and 24 weeks on the coiled side (P < 0.01). CONCLUSIONS: These results suggest that oral administration of cilostazol is an effective method of preventing thrombotic occlusion and intimal hyperplasia after stenting.

Administration, Oral↗

Mapping of murine Th1 and Th2 helper T-cell epitopes on fimbriae from Porphyromonas gingivalis.

Th1- and Th2-derived cytokine production in response to synthetic peptides of the fimbrial subunit protein (fimbrilin) from Porphyromonas gingivalis strain 381 was assessed in spleen mononuclear cells (MNC) of BALB/c mice (H-2d haplotype) immunised with the fimbrial protein antigen and adjuvant GM-53 in Freund's incomplete adjuvant (FIA). Sixty-seven sequential overlapping 10-mer peptides covering the complete 337 amino-acids (AA) protein of P. gingivalis fimbrilin were synthesised. Stimulation of spleen MNC in vitro with these 10-mer peptides resulted in the production of murine interleukin-2 (IL-2), gamma-interferon (IFN-gamma), IL-4, IL-5 and IL-6. Peptides 13 (AA 61-70), 24 (AA 116-125), 31 (AA 151-160) and 64 (AA 316-325) markedly induced IL-2 production. In particular, peptide 24 (DPLKIKRVHA), which contained I-Ad, I-Ed and I-Ak binding motifs, was the most potent stimulator of IL-2, IFN-gamma, IL-4, IL-5 and IL-6 production. Spleen MNC from C3H/HeN mice (H-2k) followed by BALB/c mice (H-2d) immunised with peptide 24 were high responders to peptide 24 in terms of both IFN-gamma and IL-4 production, whereas A/J mice (H-2a) and C57BL/6 mice (H-2b) were very low responders, P. gingivalis fimbriae evoked higher delayed-type hypersensitivity (DTH) reactions in B10.D2 (H-2d) and B10.BR (H-2k) mice followed by C57BL/10 (B10, H-2b) and B10.A (H-2a) and in guinea-pigs immunised with the fimbriae and GM-53 in FIA.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

A peptide, ALTTE, within the fimbrial subunit protein from Porphyromonas gingivalis, induces production of interleukin 6, gene expression and protein phosphorylation in human peripheral blood mononuclear cells.

Porphyromonas gingivalis 381 fimbriae and a synthetic peptide composed of residues 69-73 (ALTTE) of the fimbrial subunit protein, FP381(69-73), function in the induction of interleukin 6 (IL-6) production, IL-6 mRNA expression, and tyrosine and serine/threonine phosphorylation of several proteins in human peripheral blood mononuclear cells (PBMC). Herbimycin A and H-7, inhibitors of tyrosine kinases and protein kinase C (PKC), markedly inhibited IL-6 production, gene expression, and tyrosine and serine/threonine phosphorylation of proteins. An inactive analog of synthetic peptide replaced alanine to glycine at position 69 in FP381(69-73), GLTTE, exhibited an antagonistic effect on the IL-6 production induced by the fimbriae. These results suggest that the peptide ALTTE functions as an agent in inflammatory reactions and immune responses in the inflamed gingival and periodontal tissues, in which the participation of protein phosphorylation by tyrosine kinases and PKC in signal transduction may be considered.

Adhesins, Escherichia coli↗

[Four cases of hemolytic uremic syndrome (HUS) associated with serotype O165 verotoxin producing Escherichia coli (VTEC) identified by LPS-solid phase enzyme-linked immunosorbent assay (ELISA)].

Enzyme-linked immunosorbent assay using LPS derived from newly recognized serotype O165 verotoxin producing Escherichia coli (VTEC) could identify 4 cases of hemolytic uremic syndrome (HUS) associated with O165 VTEC. All 4 cases showed a typical clinical course seen in VTEC-associated HUS. We screened 33 cases of HUS whose pathogen was not identified by culture of serodiagnosis. The O165 serotype was not thought to be important not only as a VTEC but also as an enteropathogenic E. coli. However, the prevalence, 4 cases, was as high as of O111 serotype, which is the second major serotype of VTEC in Japan. We have to be careful for this serotype when we look for the pathogen of the patients with hemorrhagic colitis or with HUS.

Bacterial Toxins↗

Single- and multiple-dose pharmacokinetics of AM-1155, a new 6-fluoro-8-methoxy quinolone, in humans.

The pharmacokinetics of AM-1155, a new 6-fluoro-8-methoxy quinolone, was examined in healthy male volunteers after the oral administration of a single dose of 100, 200, 400, or 600 mg and multiple doses of 300 mg twice daily for 6.5 days (13 total doses). Throughout the whole study period, AM-1155 was well tolerated in every subject. In the single-dose study, the concentrations in serum reached a peak between 1 and 2 h, and the peak concentrations were 0.873, 1.71, 3.35, and 5.41 micrograms/ml at the doses of 100, 200, 400, and 600 mg, respectively. The elimination half-life was 7 to 8 h, independently of the doses. The unchanged drug was excreted mainly in the urine, with 82 to 88% of the doses appearing for 72 h. The fecal recovery of the unchanged drug amounted to 5.7% for 72 h after a single oral administration of a 400-mg dose. Urinary excretion of metabolites was minimal. The serum protein binding was 20%, independently of the concentrations in serum. The concentrations in saliva were approximately 80% of those in serum. The intake of food had no effect on the pharmacokinetic parameters and urinary excretion of AM-1155 except the slight decrease in area under the concentration-time curve. The concurrent administration of probenecid prolonged the elimination half-life, increased the area under the concentration-time curve, and decreased the apparent total body clearance, renal clearance, urinary recovery of unchanged drug, and the excretion ratio (intrinsic renal clearance of AM-1155/creatinine clearance). This indicated that the tubular secretion contributed to the renal excretion of AM-1155. In the multiple-dose study, the concentrations of AM-1155 in serum and urine reached a steady state within 2 to 3 days. The measured concentrations in serum fitted well the simulation curve, which reflected the persistence of linear pharmacokinetics of AM-1155. In conclusion, AM-1155 is expected to be clinically useful because of its potent antibacterial activity and favorable pharmacokinetics.

Adult↗

Low-threshold neuronal activity of spinal dorsal horn neurons increases during REM sleep in cats: comparison with effects of anesthesia.

1. Cats were prepared for chronic recordings from the lumbar enlargement of the spinal dorsal horn. At the beginning of each recording session, a tungsten microelectrode was advanced through the dura in a physiologically intact, awake, drug-free animal, until amplitude discrimination provided a single neuron with a receptive field on the hindquarters. 2. Extracellular recordings of activity of each neuron were made during receptive field stimulation with tactile and thermal nonnoxious and noxious stimuli. 3. Baseline responses obtained in the awake state were compared with responses of the same neurons during slow-wave or rapid-eye-movement (REM) sleep. In a subpopulation of neurons, the effects of anesthesia (propofol, 7.5 mg/kg iv) were observed after the completion of sleep studies. 4. The low-threshold receptive fields of the seven neurons studied during REM sleep were all increased in size when compared with the baseline value. The average increase was 52.6% (range 26.2-96.7%). 5. The low-threshold receptive fields of the seven neurons studied during REM sleep were reduced by propofol anesthesia by an average of 49.1% (range 29-74%). 6. Neuronal response to receptive field brushing was observed in 15 neurons during REM sleep. The effect of propofol on receptive field brushing was observed in 8 of those neurons. In only one of those eight neurons were the effects of REM sleep and anesthesia in the same direction. 7. Changes in neuronal responses were less consistent during slow-wave sleep but still differed from changes induced by propofol.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗