Search PubMed⌕ Search

Biomedical subjects

K Kubo

Publications and source records attributed to K Kubo.

At least 433 records · Page 24Linked to original sources
PubMed1993

A human monoclonal antibody that detects HLA-A1, A23 and A24 antigens.

We report the production and characterization of a human monoclonal IgM (mu, kappa) antibody recognizing the HLA A1, A23 and A24 antigens. B lymphocytes obtained from a multiparous Japanese woman were transformed in vitro by Epstein-Barr virus, screened with an immune adherence assay, and fused with a murine myeloma cell line, P3-X63-Ag8.653. After subcloning by limiting dilution three times, a stable antibody-secreting hybridoma cell line, 4-35-7, was identified. The culture supernant had a titer of 1:32-64 against each of A1-, A23- and A24-positive lymphocyte panels, and showed complete correlation (r = 1.00) with the A1, A23 and A24 antigens on a lymphocyte panel of 287 unrelated, class I HLA-typed donors by the NIH cytotoxicity assay. Monoclonality of the antibody was ensured by Southern blot analysis of the human immunoglobulin heavy chain gene of 4-35-7. In view of the published data on HLA class I nucleotide sequences, the antibody may recognize an antigeneic determinant including two amino acid residues, Asp-166 and Gly-167, in the alpha 2 helix of the class I molecule that are specific for A1, A23 and A24 so far analyzed.

Animals↗
PubMed1993

Nucleotide sequences of the variable regions of a human monoclonal antibody against HLA-A1, A23, and A24.

Nucleotide sequences of the heavy and light chain variable (VH and VL) regions of a human monoclonal antibody (4-35-7), which recognized HLA-A1, A23 and A24, were determined by means of the reverse transcriptase-polymerase chain reaction. This antibody was generated by Epstein-Barr virus transformation of lymphocytes obtained from a multiparous donor, followed by fusion with mouse myeloma cells. The VH gene segment belonged to the VHIII gene family, and used the DXP4 and JH4 gene segments. This VH gene segment had 92.9% homology to the germline gene VH26, and contained 21 nucleotide substitutions. Fourteen of them generated the replacements of amino acids, while 7 failed to generate the replacement. The ratio of replacement to silent mutations in complementarity determining regions (CDRs) was 7.0. The VL gene segment belonged to the VkI gene family, and used Jk4. This VL gene segment showed 96.1% homology to the germline gene HK102, and contained 11 nucleotide substitutions. Seven of them generated the replacement of amino acids, while 4 failed to generate the replacement. The high ratio of replacement to silent mutations in CDRs of the VH gene segment suggested that the multiparity caused the processes of antigenic selection and somatic mutation, and generated this anti-HLA antibody.

Amino Acid Sequence↗
PubMed1993

Effects of recombinant human superoxide dismutase on tumor necrosis factor-induced lung injury in awake sheep.

Tumor necrosis factor alpha (TNF) is a mediator of acute lung injury after endotoxemia, but the precise mechanism of TNF-induced lung injury remains unclear. To clarify the role of oxygen radicals, especially superoxide anion, in TNF-induced lung injury, we examined the effects of recombinant human superoxide dismutase (rhSOD; 4,200 U/mg) on lung physiological and biochemical changes after TNF infusion in awake sheep (n = 17). We prepared chronically instrumented sheep for lung lymph collection and hemodynamic monitoring. Recombinant human TNF (3.5 micrograms/kg iv) induced a biphasic response in awake sheep. Pulmonary hypertension peaked within 15 min of initiation of TNF and remained elevated for 3 h, followed by increased lung vascular permeability. rhSOD attenuated the pulmonary hypertension in both early and late phases but caused no change in the timing or magnitude of lung fluid balance changes during the late phase. Thromboxane A2 (thromboxane B2) and prostacyclin (6-ketoprostaglandin F1 alpha) metabolite levels in plasma and lymph increased after the TNF infusion, and rhSOD attenuated these changes. The intravenous infusion of rhSOD resulted in the appearance of significant levels of SOD activity in both plasma and lung lymph before and after TNF infusion. These findings suggest that superoxide anion may be implicated in the pathogenesis of the pulmonary hypertension induced by TNF in sheep.

6-Ketoprostaglandin F1 alpha↗
PubMed1993

Granulocyte colony-stimulating factor does not exacerbate endotoxin-induced lung injury in sheep.

Because it has been suggested that neutrophils play a role in endotoxin-induced lung injury, we examined the effects of increased peripheral blood-neutrophils induced by recombinant human granulocyte-colony-stimulating factor (rhG-CSF) on the lung dysfunction when induced by endotoxin in awake sheep. We prepared chronically instrumented awake sheep with lung lymph fistulae and catheters for hemodynamic monitoring. We compared alterations of pulmonary hemodynamics, lung lymph balance, circulating leukocytes, plasma and lung lymph concentrations of thromboxane B2 and 6-keto-prostaglandin F1 alpha, and arterial blood gases in sheep that received Escherichia coli endotoxin infusion intravenously (1 microgram/kg) in the following two groups: Group 1 (n = 6) received endotoxin alone, and Group 2 (n = 7) received rhG-CSF (125 micrograms/day) intravenously for 3 days before endotoxin was administered in the same manner as in Group 1. The rhG-CSF remarkably increased circulating neutrophils to 24,600 +/- 2,500/microliters in Group 2 sheep at baseline when compared with the level in Group 1 (5,700 +/- 550 microliters). After endotoxin infusion, we observed significant decreases in circulating neutrophils in both groups. There were no differences between the two groups in the time course of changes in pulmonary hemodynamics, arterial blood gases, or arachidonate products after endotoxemia. However, lung lymph flow and lung lymph protein clearance during the late phase were lower in rhG-CSF-treated sheep than in those that received only endotoxin.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1993

Effect of benidipine hydrochloride (KW-3049), on cerebral ischemia induced by bilateral occlusion of the common carotid arteries in rats.

The effect of benidipine on experimental cerebral ischemia was investigated in rats subjected to occlusion of the bilateral common carotid arteries. Benidipine (30 micrograms/kg, i.p.) improved neurological symptoms such as ataxia, convulsion and loss of righting reflex, and prolonged survival time after occlusion of the bilateral common carotid arteries. In the nicardipine (100 micrograms/kg, i.p.)-treated group, a similar effect was observed, whereas nifedipine (100, 300 micrograms/kg, i.p.) and verapamil (300 micrograms/kg, i.p.) did not show any beneficial effect in this model. Furthermore, pretreatment with benidipine (30 micrograms/kg, i.p.) suppressed the increase in cerebral water content 3 h after the occlusion. Nicardipine (100 micrograms/kg, i.p.) showed a tendency to reduce the increase in cerebral water content, though the effect was not statistically significant. Nifedipine (100 micrograms/kg, i.p.) produced no improvement. After occlusion of the bilateral common carotid arteries, depletion of adenosine triphosphate (ATP) and phosphocreatine (CP) and an accumulation of lactate occurred in a time-dependent manner. Prophylactic administration of benidipine (30 micrograms/kg, i.p.), 20 min before occlusion, attenuated the depletion of ATP and CP and the accumulation of lactate 3h after the occlusion. Furthermore, post-treatment with benidipine 30 min after occlusion also suppressed these metabolic disorders. In conclusion, the beneficial effects of benidipine in this severe cerebral ischemia model show that the compound has advantages over nicardipine, nifedipine and verapamil. Thus, these results suggest that benidipine may be useful in the treatment of acute ischemic cerebral damage.

Adenosine Triphosphate↗
PubMed1993

1,4:3,6-Dianhydrohexitol nitrate derivatives. I. Synthesis and antianginal activity of alkylpiperazine derivatives.

A series of 5-deoxy-5-(4-substituted piperazin-1-yl)-1,4: 3,6-dianhydro-L-iditol 2-nitrates was prepared and evaluated for oral anti-ischemic activities. Inhibition of lysine-vasopressin-induced T-wave elevation in the electrocardiogram (ECG) of rats (angina pectoris model) served as a primary assay. Optimum activity was observed for the compounds with the aryl-heteroatom (O,S, or N)-propyl group. Among them, the phenylthiopropyl-substituted compound 13 exhibited the most potent activity. Furthermore, intraduodenal administration (i.d.) of 13 tended to decrease left ventricular end-diastolic pressure (LVEDP) in a propranolol-induced heart failure model (dogs) and showed a potent protective effect against reperfusion arrhythmia in rats. Thus, 13 (KF 14124) is under further study as an orally active nitrate.

Administration, Oral↗
PubMed1993

1,4:3,6-Dianhydrohexitol nitrate derivatives. II. Synthesis and antianginal activity of aryl- or arylcarbonylpiperazine derivatives.

A series of 5-(4-aryl- or 4-arylcarbonylpiperazin-1-yl)-5-deoxy-1,4: 3,6-dianhydro-L-iditol 2-nitrates was prepared in order to obtain orally active, nitrate-type vasodilators with reduced side effects. Our drug design was based on a small reduction in the lipophilicity compared to that of 5-deoxy-5-[4-(3-phenylthiopropyl)piperazin-1-yl]-1,4: 3,6-dianhydro-L-iditol 2-nitrate (1, KF14124). Compounds 4h (aryl = benzimidazol-2-yl), 4i (arylcarbonyl = nicotinoyl), and 4w (arylcarbonyl = 3-furoyl) showed potent anti-ischemic activity in a lysine-vasopressin-induced angina pectoris model (rats), and their structure-activity relationships are discussed. Compound 4i exhibited potent vasodilation of the coronary artery in anesthetized dogs and also exhibited potent preload reduction in a heart failure model (dogs) as compared with isosorbide dinitrate (2), nicorandil (3), and KF14124 (1). Furthermore, 4i showed much weaker acute lethal toxicity and less central nervous system depression than 1 in mice. Thus, 4i (KW-3196) is under development as a vasodilator and a drug for treating angina pectoris.

Angina Pectoris↗
PubMed1993

High-altitude pulmonary edema with pulmonary thromboembolism.

High-altitude pulmonary edema (HAPE) is a form of noncardiogenic pulmonary edema. The pathophysiology of HAPE remains unclear. A case of HAPE was associated with pulmonary thromboembolism of a left upper pulmonary artery. Pulmonary thromboembolism was an important factor in development of HAPE in this case.

Acute Disease↗
PubMed1993

Endoscopic examination of the upper gastrointestinal tract for the presence of second primary cancers in head and neck cancer patients.

Endoscopic examination of the upper gastro-intestinal tract with Lugol's solution staining was performed on 150 patients with head and neck cancer treated at the Departments of Otolaryngology and Radiology, Osaka University Hospital, between June 1987 and December 1991. Thirteen second primary cancers (11 esophageal and 2 gastric cancers) were found endoscopically, although prior fluoroscopy had found only 4 (3 esophageal and one gastric cancer). All of the 9 second primary cancers which were not detected by fluoroscopy were in the early stage. Both Brinkman's and Alcohol indices of double primary cancer cases were significantly higher than those of single head and neck cancer cases. These results indicate that head and neck cancer patients who smoke and/or drink heavily require thorough examination of their upper gastro-intestinal tract with endoscopy, using Lugol's solution staining, as well as with fluoroscopy.

Adenocarcinoma↗
PubMed1993

Anthracycline metabolites from baumycin-producing Streptomyces sp. D788. II. New anthracycline metabolites produced by a blocked mutant strain RPM-5.

A daunorubicin-blocked mutant strain RPM-5 derived from a new baumycin-producing Streptomyces sp. D788 accumulated a major precursor metabolite D788-1 (10-carboxyl-13-deoxocarminomycin) and nine minor metabolites in the culture broth. Five among them were new with a substituent at C-10 or the altered side chains at C-9. Isolation, purification and identification of all anthracycline metabolites produced by strain RPM-5 are described with their antitumor activities against L1210 cells.

Animals↗
PubMed1993

Pharmacologic profile of endothelinA/B antagonist, [Thr18, gamma methyl Leu19]endothelin-1.

The pharmacologic profile of [Thr18,gamma methyl Leu19]endothelin-1 (TM ET-1) was investigated in several in vitro and in vivo studies. We found that TM ET-1 inhibited 125I-ET-1 binding in porcine cardiac membrane (ETA receptor) and in bovine brain membrane (ETB receptor), with IC50 values of 0.7 and 0.25 nM, respectively. These values were almost comparable to those for ET-1. TM ET-1 had no effect on intracellular Ca2+ concentration ([Ca]i) in A10 cells mediated by ETA receptors, even at 10(-5) M, or in mouse peritoneal macrophages (MPMs) mediated by ETB receptors, even at 10(-6) M. Increases in [CA]i in A10 cells by ET-1 and in MPMs by ET-3 were completely blocked by pretreatment with 10(-7) M of TM ET-1. In porcine right coronary arteries (PCAs) and in great cardiac veins (PCVs), TM ET-1 caused no contraction at concentrations < or = 10(-6) and 10(-7) M, respectively, although it competitively inhibited ET-1-induced contraction of PCAs and Ala1,3,11,15-ET-1-induced constriction of PCVs with pA2 values of 7.0 and 9.2, respectively. Furthermore, TM ET-1 was more potent than BQ123, an ETA-specific antagonist, in inhibiting the rise in perfusion pressure in a hind-limb preparation in vitro and the increase in blood pressure in rats. These results suggest that TM ET-1 is a potent ETA and ETB antagonist without agonistic effects and can be used in future studies to help clarify the physiological role of ET.

Animals↗
PubMed1993

[Maintenance therapy on the anemia in continuous ambulatory peritoneal dialysis (CAPD) patients using subcutaneous administration of recombinant human erythropoietin fortnightly--a multicenter trial].

Eighty-seven CAPD patients whose hematocrit (Ht) level was maintained by recombinant human erythropoietin (rHuEPO) were enrolled in this trial for a new formulation of rHuEPO suitable for subcutaneous injection. 6000IU rHuEPO was administered every 2 weeks for 12 weeks. Fortnightly doses were increased to 9000IU or 12000IU at 4 or 6 weeks if the Ht level decreased by 2% or more. During the study period, Ht values were maintained at the appropriate level in 88% of patients. 6000IU or lower was selected as a maintenance dose given every 2 weeks in 57 (76.0%) patients, 9000IU was selected in 8 patients and 12000IU was chosen in one patient. In 9 patients, the Ht could not be maintained during the study and the appropriate dose, therefore, remained unclear. Hypertension was observed in 2 patients as a side effect, and headache occurred in 2 other patients during the trial. Cutaneous abnormalities were not observed in the course of the subcutaneous injections. We conclude that anemia in most CAPD patients could be controlled with fortnightly injections in the dose range of 6000 to 12000IU rHuEPO given subcutaneously.

Adult↗
PubMed1993

[Clinical and pathological studies of organizing pneumonia].

Clinical and pathological studies on organizing pneumonia (OP) were performed in 16 cases diagnosed by transbronchial lung biopsy (TBLB). All patients were elderly and poorly-nourished with underlying disease, and suffered from fever and various respiratory symptoms. Results of laboratory studies in these cases were positive for C-reactive protein, negative for tuberculin reaction and showed high complement levels. Pathological findings demonstrated that there were two kinds of organizing process classified according to whether fibrin exudation was detected in Masson bodies or not. Twelve of the 16 cases were treated with prednisolone, and two cases were observed without administration. In nine of the 16 cases, abnormal shadows in chest X-ray disappeared, although abnormal shadows remained in five. Regarding the relationship between pathological findings and shadows in chest X-ray, Masson bodies without fibrin were observed in nine cases in which abnormal shadows in chest X-ray disappeared, but Masson bodies containing fibrin were observed in five cases in which abnormal shadows remained. These results suggest that there are two kinds of organizing process in OP. Steroid therapy tends to be ineffective in OP demonstrating organization containing fibrin caused probably by infection. However, prednisolone is effective in the OP associated with a fibrosing process, similar to idiopathic BOOP, without or with unrelated fibrin exudation of unknown origin.

Adult↗
PubMed1993

[Study of pathophysiology of pulmonary circulation in polycythemia using scintigraphy].

In order to evaluate the pathophysiology of pulmonary circulation in polycythemia, Tl-201 myocardial scintigraphy and perfusion lung scintigraphy with 99m-Tc MAA were performed in 19 cases with polycythemia including polycythemia rubra vera and in 11 cases with secondary polycythemia due to pulmonary diseases. Tl-201 lung uptake, right ventricular visualization and pulmonary perfusion impairment were studied. In the 19 cases, Tl-201 lung uptake was observed in all cases and 54.5% of them showed moderate lung uptake. The grade of right ventricular visualization was moderate in one case and slight in 16 cases; right ventricular hypertrophy was shown in 89.5% of all cases by Tl-201 scintigraphy, only one of which showed right ventricular hypertrophy on electrocardiography. Abnormalities of lung perfusion consisted of scattered small areas of hypoperfusion in 36.8%, peripheral hypoperfusion in 78.9% and uneven distribution of pulmonary perfusion in 94.7%. The degree of hypoperfusion was slightly related to decrease in FEV1.0%, V25 and PaO2 and increase in circulating blood volume and peripheral red blood cell counts. Abnormalities of pulmonary function consisted of increased RV/TLC in 50.0%, increased CV/VC in 35.7% and decreased V25 in 36.8%. Arterial blood gases showed hypoxemia in 57.1%, the degree of which was slightly related to increase in RV/TLC and CV/VC and decrease in V25. Cases of secondary polycythemia due to pulmonary diseases showed more marked right ventricular visualization, pulmonary perfusion impairment and abnormalities of various kinds of pulmonary function than polycythemia rubra vera cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

[A case of rheumatoid arthritis with obstructive bronchiolitis appearing after D-penicillamine therapy].

A 56-year-old woman was diagnosed as having rheumatoid arthritis in 1983. She was treated with D-penicillamine in addition to non-steroid anti-inflammatory drugs from April 1990. In August she noticed shortness of breath on exertion. Chest X-ray films showed bilateral interstitial shadows, and chest CT revealed bilateral multiple wedge-shaped shadows extending distally. Blood gas analysis showed severe hypoxemia and pulmonary function tests demonstrated decreased %VC, FEV1.0% and diffusion capacity. Open lung biopsy specimens revealed infiltration of inflammatory cells and fibrotic change in the walls of bronchioles. She was diagnosed as having obstructive bronchiolitis. Corticosteroid therapy and discontinuation of D-penicillamine therapy stopped the progression of her symptoms, and she was discharged on corticosteroid maintenance treatment and home oxygen therapy.

Arthritis, Rheumatoid↗
PubMed1993

Chest imaging with dual-energy subtraction digital tomosynthesis.

Dual-energy subtraction digital tomosynthesis with pulsed X-ray and rapid kV switching was used to examine calcifications in pulmonary lesions. The digital tomosynthesis system used included a conventional fluororadiographic TV unit with linear tomographic capabilities, a high resolution video camera, and an image processing unit. Low-voltage, high-voltage, and soft tissue subtracted or bone subtracted tomograms of any desired layer height were reconstructed from the image data acquired during a single tomographic swing. Calcifications, as well as their characteristics and distribution in pulmonary lesions, were clearly shown. The images also permitted discrimination of calcifications from dense fibrotic lesions. This technique was effective in demonstrating calcifications together with a solitary mass or disseminated nodules.

Humans↗
PubMed1993

Pharmacological profile of a highly potent and long-acting angiotensin II receptor antagonist, 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4- yl]methyl]-1H-benzimidazole-7-carboxylic acid (CV-11974), and its prodrug, (+/-)-1-(cyclohexyloxycarbonyloxy)-ethyl 2-ethoxy-1-[[2'-(1H-tetrazol-5- yl)biphenyl-4-yl]methyl]-1H-benzimidazole-7-carboxylate (TCV-116).

The angiotensin II (AII) antagonistic action of 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl-1H-benzi mid azole-7 - carboxylic acid (CV-11974) was examined in in vitro assay systems, including AII receptor binding assay using membrane fractions of bovine adrenal cortex or rabbit aorta and AII-induced contraction assay using rabbit aortic strips, and CV-11974 and its prodrug, (+/-)1-(cyclohexyloxycarbonyloxy)ethyl 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H- benzimidazole-7-carboxylate (TCV-116), were examined in an in vivo system of AII-induced pressor response in conscious rats. DuP 753 or EXP3174 (the main active metabolite of DuP 753) was used as the reference compound. CV-11974 inhibited the binding of [125I] AII to the bovine adrenal cortical membrane and rabbit aortic membrane with IC50 values of 1.12 x 10(-7) and 2.86 x 10(-8) M, respectively. Similar results were obtained with EXP3174. CV-11974 interacted with AII in these membrane fractions with subtype 1 receptor in a competitive manner. CV-11974 at 10(-5) M did not affect the binding of [125I]AII to subtype 2 (AT2) receptor in bovine cerebellum. CV-11974 selectively inhibited the AII-induced contraction of rabbit aortic strips in a noncompetitive manner (pD' 2, 9.97); it had no effects on the contraction induced by norepinephrine, KCl, serotonin, prostaglandin F2 alpha or endothelin. EXP3174 showed a pD'2 value of 8.95 for the AII-induced contraction. CV-11974 given intravenously and TCV-116 given orally inhibited the AII-induced pressor response in rats with ID50 values of 0.033 mg/kg and 0.069 mg/kg, respectively. These effects of CV-11974 and TCV-116 were 12 and 48 times more potent than those of EXP3174 and DuP 753, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex↗