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Biomedical subjects

K Kubo

Publications and source records attributed to K Kubo.

At least 19 recordsLinked to original sources
PubMed1997

Low pulmonary diffusing capacity in subjects with acute mountain sickness.

This study was conducted to investigate whether the changes in the pulmonary diffusing capacity found in individuals with acute mountain sickness (AMS) reflect the early stage of high-altitude pulmonary edema (HAPE). We measured the pulmonary diffusion capacity for carbon monoxide (DCO) by the single-breath method, arterialized capillary blood gas, and spirometry in a group of 32 healthy subjects (24 men, eight women) at an altitude of 2,260 m and after ascent to 4,700 m. Twelve subjects (10 men, two women) had symptoms of AMS (AMS group) by the second day after arrival at 4,700 m, but none had clinical signs of pulmonary or cerebral edema. In the non-AMS group, almost all subjects exhibited an increase in DCO at 2,260 to 4,700 m (delta DCO, 10.7 +/- 1.25 mL/min/mm Hg), while the degree of increase in DCO in the AMS group (n = 12) was significantly lower (delta DCO, 1.26 +/- 1.74 mL/min/mm Hg) than that of the non-AMS group (p < 0.01). In four of the 12 subjects with AMS who had a high AMS score, DCO decreased from 38.4 +/- 4.5 to 33.2 +/- 5.3 mL/min/mm Hg (delta DCO, -5.84 +/- 1.1 mL/min/mm Hg). The AMS group showed significantly lower vital capacity, forced expiratory flow during the middle half of FVC, PaO2, and a greater alveolar-arterial oxygen pressure difference at 4,700 m compared with the non-AMS group. DCO showed a significant negative correlation with AMS score (r = -0.885) and a positive correlation with PaO2 (r = 0.757) at 4,700 m. These results suggest that the decreased pulmonary diffusing capacity in subjects with AMS reflects the presence of pulmonary gas exchange abnormality, which is probably due to subclinical interstitial edema of the lung.

Acute Disease↗
PubMed1996

Synthesis and angiotensin II receptor antagonistic activities of benzimidazole derivatives bearing acidic heterocycles as novel tetrazole bioisosteres.

The design, synthesis, and biological activity of benzimidazole-7-carboxylic acids bearing 5-oxo-1,2,4-oxadiazole, 5-oxo-1,2,4-thiadiazole, 5-thioxo-1,2,4-oxadiazole, and 2-oxo-1,2,3,5-oxathiadiazole rings are described. These compounds were efficiently prepared from the key intermediates, the amidoximes 4. The synthesized compounds were evaluated for in vitro and in vivo angiotensin II (AII) receptor antagonistic activities. Most were found to have high affinity for the AT1 receptor (IC50 value, 10(-6)-10(-7)M) and to inhibit the AII-induced pressor response (more than 50% inhibition at 1 mg/kg po). The 5-oxo-1,2,4-oxadiazole, 5-oxo-1,2,4-thiadiazole, and 5-thioxo-1,2,4-oxadiazole derivatives showed stronger inhibitory effects than the corresponding tetrazole derivatives, while their binding affinities were weaker. This might be ascribed to their improved bioavailability by increased lipophilicity. The 5-oxo-1,2,4-oxadiazole derivative 2 (TAK-536) and 5-oxo-1,2,4-thiadiazole derivative 8f showed efficient oral bioavailability without prodrug formation. This study showed that the 5-oxo-1,2,4-oxadiazole ring and its thio analog, the 5-oxo-1,2,4-thiadiazole ring, could be lipophilic bioisosteres for the tetrazole ring in nonpeptide AII receptor antagonists.

Angiotensin Receptor Antagonists↗
PubMed1996

Identification of metallothionein isoforms with capillary zone electrophoresis using a polyacrylamide-coated tube.

Metallothionein (MT) isoforms from various liver tissues were separated with capillary zone electrophoresis (CZE) using a polyacrylamide-coated tube at neutral pH. The electrophoresis was performed on MT-1 and MT-2 purified from mouse, rat, rabbit and human livers. The retention times of mouse and rat MT-1 coincided, while the retention times of rabbit and human MT-1 were longer. The retention times of MT-2 purified from the four sources were the same. MT-1 and MT-2 separated more definitely with N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES)-Tris buffer (25 mM, pH 7.4) than with N-tris(hydroxymethyl)methyl-3-aminopropane sulfonic acid (TAPS)-Tris buffer (25 mM, pH 7.7) or with N-(2-acetamido)iminodiacetic acid (ADA)-Tris buffer (25 mM, pH 7.4). In addition, liver MT isoforms prepared from Zn- or Cd-administered mice could be separated.

Acrylic Resins↗
PubMed1996

Rapid electrophoretic analysis of heterogeneity of bovine serum albumin using a linear polyacrylamide-coated capillary.

Bovine serum albumin was separated into three major peaks and two or three minor peaks at pH 7.4 within 12 min by capillary zone electrophoresis using a linear polyacrylamide-coated capillary. The two major peaks, having medium and low mobilities, were assigned to the monomers of nonmercaptoalbumin and mercaptoalbumin, respectively. On the other hand, cross-linked albumins were distributed as a broad peak around the major peak with high mobility. Thus, commercially available bovine serum albumins from various sources were revealed to have a wide variety of heterogeneity in terms of their respective components.

Animals↗
PubMed1996

Bradykinin stimulates alveolar macrophages to release neutrophil, monocyte, and eosinophil chemotactic activity.

Bronchial asthma is accompanied with inflammatory cell infiltration in the airway. Because kinin activity was detected in bronchoalveolar lavage fluid (BALF) from asthmatic patients, and because the concentrations of kallikrein and kinins in BALF increased after allergen challenge, we evaluated the potential that bradykinin (BK) might stimulate alveolar macrophages (AM) to release neutrophil, monocyte, and eosinophil chemotactic activity (NCA, MCA, and ECA). To test this hypothesis, bovine AM were isolated by bronchoalveolar lavage and cultured. The supernatant fluids of AM were tested for chemotactic activity by a blind well chamber technique. AM released NCA, MCA, and ECA in response to BK in a dose-and time-dependent manner (p < 0.01). The released activities were chemotactic by checkerboard analysis. Partial characterization and molecular sieve column chromatography revealed that these released activities were heterogeneous, suggesting predominant low-m.w. lipid soluble activity and weak high-m.w. peptide activity. Lipoxygenase inhibitors blocked the release of chemotactic activities (p < 0.01). The chemotactic activities were partly inhibited by leukotriene B4 (LTB4) and platelet-activating factor (PAF) receptor antagonists (p < 0.05, respectively). Immunoreactive LTB4 significantly increased in supernatant fluids in response to BK (p < 0.05), but PAF was detected only two out of six samples stimulated by BK. The receptor responsible for the release of LTB4 involved both BKB1 and BKB2 receptors. These data suggest that BK may stimulate AM and play a role in bronchial inflammation by recruiting inflammatory cells into the airway.

Animals↗
PubMed1996

Assessment of autonomic nervous function by power spectral analysis of heart rate variability in the horse.

We studied power spectral analysis of heart rate (HR) variability in the horse, with the hypothesis that the quantitative information provided by the spectral analysis of HR variability reflects the interaction between sympathetic and parasympathetic regulatory activities. For this purpose, electrocardiogram, blood pressure (BP) and respiratory (Resp) waveform were simultaneously recorded from Thoroughbred horses (3-5 years old) and analyzed by power spectrum. There were two major spectral components at low-frequency (LF) and high-frequency (HF) bands for HR variability. The peak of Resp variability clearly occurred at the HF range. In contrast to Resp variability, the power spectra of BP variability occurred at lower frequencies. The maximum coherence between HR and Resp variabilities and HR and BP variabilities occurred at approximately 0.15 and approximately 0.03 Hz, respectively. These relationships were similar to the ensemble spectra. On the basis of these data, we have defined two frequency bands of interest: LF (0.01-0.07 Hz) and HF (0.07-0.6 Hz). Therefore, we believe that power spectral analysis of HR variability provides a very powerful technique for assessing autonomic nervous activity in the horse.

Animals↗
PubMed1996

Influence of opioid peptides on the priming action of estrogen on lordosis in ovariectomized rats.

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.

Animals↗
PubMed1996

Effects of a new endothelin receptor antagonist, TAK-044, on myocardial stunning in dogs.

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.

Animals↗
PubMed1996

A monoclonal antibody KIS-1 recognizing a new membrane antigen on human squamous-cell carcinoma.

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.

Animals↗
PubMed1996

Different T-cell receptor repertoires between lesions and peripheral blood in acute graft-versus-host disease after allogeneic bone marrow transplantation.

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.

Acute Disease↗
PubMed1996

Studies of cardiotonic agents. 8. Synthesis and biological activities of optically active 6-(4-(benzylamino)-7-quinazolinyl)-4,5-dihydro-5-methyl-3(2H)- pyridazinone (KF15232).

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.

Animals↗
PubMed1996

Analysis of interaction between cadmium and metallothionein isoforms by capillary zone electrophoresis.

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.

Animals↗
PubMed1996

Eosinophil chemotactic activity in bronchoalveolar lavage fluid obtained from Toxocara canis-infected rats.

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.

Animals↗
PubMed1996

Effects of altered FIO2 on maximum VO2 in the horse.

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.

Animals↗
PubMed1996

Presence and structure of anal and vaginal tonsils in the laboratory shrew (Suncus murinus).

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.

Anal Canal↗
PubMed1996

Magnetic resonance imaging of neurogenic tumors of the thoracic inlet: determination of the parent nerve.

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.

Brachial Plexus↗