Biomedical subjects
Publications and source records attributed to K Kubo.
Lordosis in response to male mounting in estrogen-progesterone primed ovariectomized rats was facilitated by beta-endorphin or metenkephalin but inhibited by leu-enkephalin if the peptides were injected into third ventricle at the time of estrogen-priming. It is suggested that opioidergic systems modulate the activation of the estrogen-dependent brain functions that control lordosis.
The effects of a new endothelin receptor antagonist, TAK-044, (cyclo[D-alpha-aspartyl-3-[(4-phenylpiperazin-1-yl)carbonyl]L-alan yl-L-alpha aspartyl-D-2-(2-thienyl)glycyl-L-leucyl-D-tryptophyl]disodium salt, on ischemic and post-ischemic myocardial dysfunction (stunned myocardium) were studied in anesthetized open-chest dogs. A short (15 min) occlusion of the left anterior descending coronary artery followed by 5-h reperfusion significantly reduced myocardial segment shortening during and after the ischemic period in the ischemic region. Regional myocardial blood flow was also decreased significantly 10 min after the occlusion, whereas it returned almost completely to its pre-ischemic value 5 h after reperfusion TAK-044 (3 mg/kg,i.v.) administered 10 min before occlusion significantly improved the reduced myocardial segment shortening in the ischemic region during and after occlusion. Cardiovascular hemodynamics and regional myocardial blood flow in a TAK-044-treated group were identical to those in the control group. These results indicate that endogenous endothelin contributes to the cause of ischemic and post-ischemic myocardial dysfunction without changing either hemodynamics or regional myocardial blood flow.
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A KIS-1 monoclonal antibody (MAb) (IgG1, kappa) recognizing a membrane antigen on human squamous-cell carcinomas (SCC) was developed to understand their antigenicity using an esophageal SCC as an immunogen. The KIS-1 MAb recognized a membrane antigen on a majority of esophageal, lung, and oral- cavity SCC by immunofluorescent and by immunohistochemical analyses. In contrast, it showed little reactivity to adenocarcinomas from different organs, and none to keratinocyte cell lines. This MAb showed reactivity to the cells in the basal layer of normal esophageal epithelium adjacent to the esophageal SCC, but none of the other normal tissues, including esophageal epithelium far from the SCC and that from patients with non-malignant disease. The KIS-1 MAb immunoprecipitated a 46-kDa membrane protein of the esophageal SCC in non-reducing and in reducing conditions. It recognized the 46- and the 40-kDa proteins of the esophageal SCC by immunoblot analysis. These results suggest that the KIS-1 MAb recognizes a new membrane antigen preferentially expressed on SCC, and that this antigenicity is shared only by the cells in the basal layer of the esophageal epithelium adjacent to SCC. The KIS-1 MAb may be a new tool for understanding the antigenicity of SCC.
From the viewpoint of T-cell receptor (TCR) repertoire, we studied the role of T cells in acute graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation (allo-BMT) from an HLA-identical sibling. By means of inverse polymerase chain reaction method and DNA sequencing, we analyzed TCR-alpha and -beta transcripts from GVHD lesions and peripheral blood (PB) in a patient with typical GVHD together with PB from donor. At the initial onset of GVHD, V alpha-7 and -19 subfamilies were oligoclonally expanded in the PB compared with those in the oral mucosal lesions. At the second onset, V alpha-2, and V beta-6 subfamilies were more frequently detected in the cutaneous lesion than in the PB. Some TCR transcripts were recurrently found either in the mucosal or cutaneous lesions (or in both) and not in the PB. Furthermore, some of recurrent TCR transcripts in the lesions shared V gene segments and common motifs of complementarity determining region-3. These findings suggested that T cells infiltrating the GVHD lesions recognized a limited kind of antigens presented by patient's tissues with GVHD, and that T-cell repertoire in the GVHD lesions was different from that in the PB.
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We previously reported that (+/-)-6-(4-(benzylamino)-7-quinazolinyl)-4,5- dihydro-5-methyl-3(2H)-pyridazinone (+/-)-1, KF15232) showed potent cardiotonic activity with a strong myofibrillar Ca(2+)-sensitizing effect. As an extension of our work, we attempted to synthesize optically active 1. (+/-)-4-(4-(Benzylamino)-7-quinazolinyl)-3-methyl-4-oxobutyric acid (-)-menthyl ester (6) was separated into both diastereoisomers, and each was converted to optically pure 1 (> 99% ee) in an enantioselective manner. In order to determine the absolute configuration of the isomers, an alternative synthesis of optically active 1 was employed. The precursor of (-)-1 ((+)-9) was obtained by enantioselective synthesis from (R)-D-alanine. Consequently, we concluded that the absolute configuration of (-)-1 at the 5-position of the pyridazinone ring was R. The cardiotonic effects and inhibitory activities to PDE III and V of racemic 1 and (-)-1 were more potent than those of (+)-1. These compounds also demonstrated greater vasorelaxant effects in guinea pig aorta. In contrast, (+)-1 showed only weak cardiotonic and vasodilating effects, although the compound displayed potent Ca(2+)-sensitizing activity. Racemic and (-)-1 attracted our interest for the treatment of congestive heart failure.
The effects of cadmium on the peak area of metallothionein (MT) protein were studied by capillary zone electrophoresis with a polyacrylamide-coated tube at neutral pH. When cadmium was added to a commercial standard MT-1 isoform prepared from rabbit liver, the peak are of the MT-1 isoform decreased in a time- and dose-dependent manner. The MT-2 isoform also decreased with time, but the rate of decrease was lower than that of the MT-1 isoform. When ethylene glyco-bis-(beta-aminoethyl ether)-N,N,N'N'-tetraacetic acid (EGTA) was added to a solution containing cadmium and MT-1, the peak area recovered with increasing concentration of EGTA. Zinc caused a slight decrease in the peak areas of MT-1 and MT-2 compared with cadmium, while addition of sodium did not decrease the areas. Furthermore, the peak areas of MT isoforms of the crude extract prepared from zinc-treated mice also decreased with increasing concentration of cadmium. These results indicate that cadmium may changed the charge of MT, which may account for the observed differences in electrophoretic behavior.
We examined eosinophil chemotactic activity (ECA) in bronchoalveolar lavage fluid (BALF) obtained from rats infected with Toxocara canis. For 4 weeks after infection, the number of eosinophils was determined in peripheral blood and BALF. ECA was assayed using a microchemotaxis chamber. Eosinophils in peripheral blood and BALF increased markedly after infection, peaking at 12 days and 2 weeks, respectively. ECA in BALF also increased significantly and peaked 2 weeks after infection. Partial characterization revealed that ECA was heat labile, lipid soluble, and resistant to trypsin digestion. Two ECA peaks were identified by molecular sieve column chromatography: one near the egg albumin marker (MW 45,000) and the other observed after elution with quinacrine (MW 472.9). Treatment with a specific leukotriene (LT) B4 receptor antagonist (ONO-4057), a platelet activating factor (PAF) receptor antagonist (TCV-309), and an anti-interleukin (IL)-5 monoclonal antibody (TB13) significantly reduced the ECA, suggesting that LTB4, PAF, and IL-5 contribute to the accumulation of eosinophils in the lungs of rats infected with T. canis.
Although the horse is considered an elite athlete with a specific VO2max some 2-4 times higher than man, maximal O2 transport is compromised both by moderately severe arterial desaturation and by failure to extract all O2 from blood perfusing exercising muscle. This prompted the present study to ascertain whether correction of arterial desaturation would proportionally augment VO2max and, if so, would O2 extraction behave in a manner predicted by diffusional transport limitation. Six two year old thoroughbreds were exercised to VO2max on a treadmill each on three separate occasions breathing gases of FIO2 = 0.15, 0.21 and 0.35, each used once in balanced order. VO2, ventilation, arterial and pulmonary arterial blood gases, pressures and lactate levels were measured both submaximally and maximally at each FIO2 and cardiac output was computed by mass balance for O2. At FIO2 = 0.21, VO2max = 143.9 +/- 4.8 ml kg-1 min-1, arterial saturation (SaO2) was 81.6 +/- 3.3% while venous PO2 (PvO2) was 15.3 +/- 1.4 Torr. At FIO2 = 0.35, VO2max was 172.6 +/- 8.2 ml kg-1 min-1, SaO2 reached 97.4 +/- 0.4% and PvO2 was 23.4 +/- 0.7 Torr. VO2max at FIO2 = 0.15 was 109.8 +/- 4.1 ml kg-1 min-1, SaO2 fell to 68.1 +/- 2.5% and PvO2 was 10.6 +/- 1.0 Torr, all changes being significant, p < 0.01. As FIO2 was varied, VO2max changed proportionally to calculated mean capillary Po2 as well as to total O2 delivery. These data confirm substantial O2 supply dependence of VO2max in the horse, and in such a manner as to be consistent with the hypothesis of combined diffusive and convective transport limitation within muscle.
In all the laboratory shrews (Suncus murinus) examined, a pair of tonsil-like structures was found at the boundary between the anus and the ostium urogenitoanalis. Moreover, the same tissues were recognized between the vagina and the ostium urogenitoanalis in 9 of the 13 females examined. They indicated clear epitheliolymphocyte symbiosis around both mucosal crypts (anal and vaginal crypts) and outer lymph nodules including the germinal centers, and were demarcated from other tissues by the fibrous capsule. Two kinds of tonsil-like structures in this study were found to be homologous with some of the tonsils in the fauces of other mammals. These will be therefore referred to as the anal and vaginal tonsils.
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To investigate the value of magnetic resonance imaging (MRI) in determining the parent nerves of neurogenic tumors in the thoracic inlet, analysis of MR images was performed in nine patients with surgically resected neurogenic tumors in the thoracic inlet (two neurofibromas and one schwannoma of the vagus nerve, three schwannomas of the brachial plexus, and two schwannomas and one ganglioneuroma of the sympathetic nerves). These MR images were compared with surgical and pathologic findings. The multidirectional capability and excellent tissue contrast of MRI facilitated recognition of the location, shape, and extent of the tumors. MRI, which permitted an easy understanding of the spatial relation between the tumors and the subclavian vessels, scalenus muscles, and brachial plexus, was useful in determining the nerves of origin. Two neurofibromas, four of six schwannomas, and one ganglioneuroma were recognized to extend along the axes of the parent nerves on MR images. MRI is useful in determining the parent nerve of neurogenic tumors in the thoracic inlet and is helpful in planning surgical treatment of these tumors.
This study assessed the fibronectin expression by fibroblasts derived from noninflamed and inflamed gingiva by measuring the amount of cell surface-associated fibronectin and fibronectin released into the medium. The effects of added lipopolysaccharide from Porphyromonas gingivalis, Prevotella nigrescens and Escherichia coli on both types of fibroblasts were also studied. In the absence of lipopolysaccharide, the amounts of the two types of fibronectin were significantly larger in the fibroblasts from inflamed than from noninflamed gingiva. The specific lipopolysaccharide had no effect on the amount of fibronectin released into the medium by either fibroblast type. The amount of cell surface-associated fibronectin increased significantly when lipopolysaccharide (0.1 and 1 microgram/ml) was added to the cells from the noninflamed gingiva (the effect was evident in the order: P. gingivalis>P.nigrescens>E. coli). Lipopolysaccharide from P. gingivalis significantly increased the cell surface-associated fibronectin even at a low concentration of lipopolysaccharide (0.01 microgram/ml). In fibroblasts from the inflamed gingiva, only the lipopolysaccharide from P. gingivalis was effective in increasing the amount of cell surface-associated fibronectin. Our findings showed that the fibronectin expression was increased in the fibroblasts from inflamed gingiva and that lipopolysaccharide from P. gingivalis increased the cell surface-associated fibronectin.
BACKGROUND: Hepatitis C virus (HCV) infection has recently been incriminated as an aetiological agent in idiopathic pulmonary fibrosis. This study was performed to determine the cellularity and lymphocyte phenotypes of bronchoalveolar lavage (BAL) fluid in patients with chronic hepatitis C. METHODS: BAL fluid and lavage lymphocyte subsets from 13 patients (10 men) with active chronic hepatitis C, diagnosed by sustained elevated serum glutamic pyruvic transaminase and typical histological findings in the liver, were analysed. Lavage findings in these patients were compared with those from 13 healthy volunteers (eight men) as controls. RESULTS: There was no difference in total cell counts in lavage fluid between the two groups. Lavage lymphocyte and eosinophil numbers were increased in patients with chronic hepatitis C. Surface marker analysis of the lymphocyte populations showed increases in CD2, CD3, CD4, and HLA-DR. CD4/CD8 ratios were not different. CONCLUSIONS: The numbers of lymphocytes and eosinophils in BAL fluid are increased in patients with chronic hepatitis C. These findings suggest that HCV infection may trigger alveolitis.
BACKGROUND: The precise mechanism of high altitude pulmonary oedema (HAPE) remains unclear. The purpose of this study was to evaluate the role of cytokines and P-selectin in the development of HAPE which occurred at moderate altitude in Japan. METHODS: The following cellular and biochemical markers and chemotactic cytokines were measured in the bronchoalveolar (BAL) fluid from four patients with HAPE at 2857-3180 m in the Japanese Alps: total proteins, albumin, lactate dehydrogenase (LDH), and interleukin (IL)-1 alpha, IL-1 beta, IL-1 receptor antagonist (ra), IL-6, IL-8, IL-10, tumour necrosis factor (TNF)-alpha, and the soluble form of P-selectin. RESULTS: At admission there were significant increases in the levels of total cells, especially macrophages and neutrophils, total protein, albumin and LDH when compared with 13 healthy individuals. Furthermore, the levels of IL-1 beta, IL-6, IL-8, and TNF-alpha were also considerably increased but returned quickly to the normal ranges or were not detected after recovery. The levels of IL-1 alpha, IL-10, and P-selectin did not change. CONCLUSIONS: These results suggest that an inflammatory process almost identical with acute respiratory distress syndrome (ARDS) may occur in HAPE, but that these changes are transient and are not associated with any increase in P-selectin levels in the BAL fluid.
We have previously shown in sheep that pulmonary vascular resistance decreases rapidly after the onset of constant exercise, followed by a slower and smaller second vasodilation. The second phase is partly regulated by alpha- and beta-adrenoceptor activation. We examined the effect of inhaled nitric oxide (NO; 40 ppm) and intravenous nitroglycerin on beta-adrenergic blockade-induced pulmonary vasoconstriction during exercise. In paired studies, we exercised eight sheep at a constant rate of 4 miles per hour for 4 min on a treadmill and measured the hemodynamic response during beta-blockade (propranolol, 1 mg i.v.) with and without 40 ppm inhaled NO or continuous infusion of nitroglycerin (3.2-4.0 micrograms.kg-1.min-1). beta-Blockade resulted in a higher pulmonary vascular resistance during steady-state exercise (40-240 s) than in the unblocked state; reduction in pulmonary vascular resistance during the second phase of exercise was smaller with beta-blockade (13-16%) than with control exercise (26-30%). Inhaled NO and nitroglycerin reversed the beta-blockade-related pulmonary vasoconstriction to the levels of control exercise. Inhaled NO and intravenous nitroglycerin also reversed the pulmonary vasoconstriction produced by intravenous phenylephrine at rest. We conclude that exogenous NO, delivered by gas inhalation or via nitroso compounds, opposes and fully reverses alpha-receptor-activated pulmonary vasoconstriction during exercise in sheep.