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Biomedical subjects

K Kubo

Publications and source records attributed to K Kubo.

At least 199 records · Page 11Linked to original sources
PubMed1999

Improvements in thoracic movement following lung volume reduction surgery in patients with severe emphysema.

In twelve patients with severe emphysema who underwent lung volume reduction surgery (LVRS), we assessed the results of dyspnea scale, pulmonary function, 6-minute walk distance (6MD), and thoracic movement prior to and 6 months following LVRS. Postoperatively, forced expiratory volume (FEV1), maximum inspiratory mouth pressures (MIP), maximum expiratory mouth pressures (MEP), maximum voluntary ventilation (MVV), diffusing capacity for carbon monoxide (DLCO), partial pressure of oxygen (PaO2) and 6MD were significantly increased with the decrease in dyspnea scale and lung hyperinflation. Thoracic movement, as assessed by the bilateral lung area ratio of the mid-sagittal dimension of dynamic magnetic resonance imaging (MRI) at full inspiration to that at full expiration, was significantly increased. The improvement in thoracic movement was significantly correlated with the increases in FEV1, MVV, and MIP, and with the decrease in residual volume (RV), and with the improvement in the dyspnea scale. These findings suggest that LVRS is an effective procedure for improving not only the airflow limitation and gas exchange but also the thoracic movement in severe emphysema, and these improvements may contribute to an increase in exercise performance and relief of dyspnea.

Aged↗
PubMed1999

[Tuberculous meningitis developed during treatment for systemic lupus erythematosus (SLE)].

A 51-year-old woman was admitted to our hospital complaining of fever and general fatigue. Physical examination revealed butterfly-like erythema in face, facial edema and diffuse purpura all over her body. Laboratory data showed renal dysfunction, nephrotic syndrome and active phase of SLE. She was administered first methylprednisolone (1g/day/3 days by intravenous drip) then prednisolone (60 mg/day/month, orally) and had immune adsorption therapy for eight times. However, 14 days after the last session of immune adsorption, she developed fever of 39 degrees C and mild headache, and then 3 days later, she gradually became unconscious. Brain CT showed hydrocephalus. We diagnosed her as having tuberculous meningitis based on the detection of acid-fast bacillus in cerebrospinal fluid, and began treatment with antituberculous agents. We suspected that tuberculous meningitis had caused hydrocephalus. We tried percutaneous drainage of the left ventricle for hydrocephalus. Brain MRI showed a tuberculoma depicted as a mass of low intensity in the right cerebellum on the T1-weighted image, and of high intensity on the T2-weighted image, and the meninx in the basal cistern was enhanced. After treatment with antituberculous agents, we performed serial brain MRI and examined cerebrospinal adenosine deaminase activity (ADA). Despite treatment with antituberculous agents, new intracerebral tuberculomas had developed in some areas, whereas they had disappeared in other areas. After treatment for 4 months, the level of cerebrospinal ADA became normal, and the patient recovered consciousness despite the presence of multiple tuberculomas. Both the cell counts and the level of ADA in cerebrospinal fluid are the good indicators of the activity of tuberculous meningitis and reflected its clinical course. Furthermore, the level of ADA in cerebrospinal fluid changed with brain MRI image. Serial brain MRI and examination of ADA in cerebrospinal fluid were useful to know the activity of tuberculous meningitis and to evaluate the response to treatment.

Adenosine Deaminase↗
PubMed1999

Ultrastructural studies on the formation and distribution of lipid droplets in the lung capillary endothelial cells in patients with sarcoidosis.

BACKGROUND AND AIM OF THE WORK: We previously reported the presence of definite morphological alterations in the capillary endothelium of sarcoid lung. The aim of this study was to examine ultrastructural changes and distribution of lipid droplets in the endothelium of lung capillaries of patients with sarcoidosis. METHODS: Tissue specimens were obtained by transbronchial lung biopsy or open lung biopsy from 16 patients with sarcoidosis and 13 controls. Biopsies were evaluated by electron microscopy following lead citrate and uranyl acetate staining. RESULTS: Typical lipid droplets were observed in pulmonary capillaries of 11 out of 16 sarcoid patients (69%); the droplet frequency was higher in sarcoid patients than in control specimens. Lipid droplets were characterized by biphasic density: most droplets contained eccentrically located vacuoles (saturated fatty acids) others were characterized by low density areas (unsaturated fatty acids). Biphasic droplets were covered by large lysosomal granules and were mainly distributed in the endothelium and pericytes. Interestingly, in the latter, vacuoles increased in size while small amounts of lysosomal granules were detectable. CONCLUSION: Our findings suggest that biphasic droplets increase in number in pulmonary capillaries of patients with sarcoidosis with a characteristic distribution pattern from the endothelium to pericytes.

Adult↗
PubMed1999

A new class of diacidic nonpeptide angiotensin II receptor antagonists: candesartan cilexetil.

Blockade of the action of angiotensin II (AII) has long been a target for development of novel antihypertensive agents. We recently discovered a novel class of potent nonpeptide AII receptor antagonists, benzimidazole-7-carboxylic acids including candesartan. Candesartan is a highly potent and insurmountable angiotensin II type-1 receptor (AT1)-selective antagonist. Structure-activity relationship (SAR) studies revealed that the adjacent arrangement of a lipophilic substituent, a tetrazolylbiphenylmethyl moiety and a carboxyl group was the important structural requirement for potent AII antagonistic activity. The benzimidazole ring was found to be one of the most suitable templates arranging these three essential components in correct direction. Especially, the presence of a carboxyl group at the 7-position was found to be essential for insurmountable antagonism. Although candesartan is a very potent AII antagonist, it was found to be absorbed rather inefficiently upon oral administration. To improve bioavailability (BA) of candesartan, chemical modification was examined to yield candesartan cilexetil, a prodrug of candesartan. Candesartan cilexetil is a potent and long-acting blocker that provides effective 24 hr blood pressure control. Our alternative research efforts to improve oral BA was performed by replacement of the tetrazole ring in candesartan by other new acidic bioisosteric heterocyclic rings to find the nonprodrug AII antagonist TAK-536, bearing 5-oxo-1,2,4-oxadiazole ring, which was as potent and orally active as candesartan cilexetil.

Angiotensin Receptor Antagonists↗
PubMed1999

[Estimation of pulmonary hypertension in lung and valvular heart diseases by perfusion lung scintigraphy].

To estimate pulmonary hypertension, we measured postural differences in pulmonary blood flow for the lateral decubitus positions on perfusion lung scintigrams with Tc-99 m macro-aggregated albumin, applying the method devised by Tanaka et al (Eur J Nucl Med 17: 320-326, 1990). Utilizing a scintillation camera coupled to a minicomputer system, changes in the distribution of pulmonary blood flow caused by gravitational effects, namely, changes in the total count ratios for the right lung versus the left lung in the right and left lateral decubitus positions (R/L), were obtained for 44 patients with lung disease, 95 patients with valvular heart disease, and 23 normal subjects. Mean standard deviation in the R/L ratios was 3.09 +/- 1.28 for the normal subjects, 1.97 +/- 0.89 for the patients with lung disease, and 1.59 +/- 0.59 for the patients with valvular heart disease. The R/L ratios correlated with mean pulmonary arterial pressure and cardio-thoracic ratios in the lung disease and valvular heart disease groups, with pulmonary arteriolar resistance in the former, and with pulmonary capillary wedge pressure in the latter. Defining pulmonary hypertension (> 20 mmHg) as an R/L ratio of less than 1.81, which is the mean-1 standard deviation for normal subjects, the sensitivity and the specificity of the R/L ratio for the diagnosis of pulmonary hypertension were 62.9% and 76.2%, respectively, for the lung disease patients, and 80.3% and 61.8%, respectively, for the valvular heart disease patients. This method seems to be useful for the pathophysiologic evaluation of pulmonary perfusion in cases of lung disease and valvular heart disease.

Adult↗
PubMed1999

A new class of diacidic nonpeptide angiotensin II receptor antagonists: candesartan cilexetil.

Blockade of the action of angiotensin ii (AII) has long been a target for development of novel antihypertensive agents. We recently discovered a novel class of potent non-peptide AII receptor antagonists, benzimidazole-7-carboxylic acids including candesartan. Candesartan is a highly potent and insurmountable antagonist selective in the angiotensin II type-I receptor (AT1). Structure-activity relationship (SAR) studies revealed that the adjacent arrangement of a lipophilic substituent, a tetrazolylbiphenylmethyl moiety and a carboxyl group was the important structural requirement for potent AII antagonistic activity. Especially, the presence of a carboxyl group at the 7-position was found to be essential for insurmountable antagonism. To improve bioavailability of candesartan, chemical modification was examined to yield candesartan cilexetil, a prodrug of candesartan. Candesartan cilexetil is a potent and long-acting blocker that, when given once-daily to patients, provides effective 24 hr blood pressure control.

Angiotensin II↗
PubMed1999

[Primary ciliary dyskinesia treated with living-donor lobar lung transplantation].

We report a case of primary ciliary dyskinesia in which a living-donor lobar lung transplant was performed. A 24-year-old woman with a diagnosis of primary ciliary dyskinesia and bronchiectasis was admitted to Shinshu University Hospital because of persistent dyspnea and pyrexia over a period of 4 months. Although she was given various antibiotics, neutrophilia, elevated plasma C-reactive protein (CRP) levels, and respiratory failure persisted. Chest roentgenograms and computed tomography disclosed severe bronchiectasis and diffuse infiltrative shadows in both lung fields. Pseudomonas aeruginosa was detected in a sputum culture. Although a variety of conventional therapies were administered, the patient's oxygenation progressively deteriorated. She was intubated and assisted by mechanical ventilation. The patient and her family proposed lung transplantation, and we concluded that a living-donor lobar lung transplant would be a suitable treatment for her disease. We transported the patient to Okayama University Hospital by helicopter 10 days after intubation. A living-donor lobar lung transplant was successfully performed with lung tissues donated by the patient's mother and sister for each transplant site.

Adult↗
PubMed1999

Incidence of histamine release after the administration of midazolam-ketamine in allergic patients.

OBJECTIVE: We examined the effects of midazolam-ketamine which was used during the induction of anesthesia against histamine release, skin reactions and hemodynamic changes in patients with a history of allergy. SUBJECTS: Forty allergic patients and 40 non-allergic patients undergoing oral surgery were examined. METHODS: Midazolam ketamine was used for the induction of anesthesia in 40 patients with a history of allergy (M-K group) and thiamylal was used for the induction of anesthesia in 40 patients without any history of allergy (BARB group). Venous blood samples were obtained before induction as a control and 0.5, 1, 3, 5 minutes after the administration of each drug in order to measure the plasma histamine level. In addition, any observed hemodynamic changes were simultaneously recorded. The plasma histamine level was measured using the HPLC (high performance liquid chromatography) post-label system. RESULTS: The incidence of histamine release, skin reactions and hemodynamic changes were 37.5%, 10.0% and 7.5%, in the M-K group, and 40.0%, 12.5% and 12.5%, in the BARB group, respectively. Although the mean basal plasma histamine level in the M-K group (0.46 +/- 0.23 ng/ml) who had a history of allergy was much higher than that in the BARB group (0.28 +/- 0.17 ng/ml) (p < 0.001), the incidence of histamine release and clinical symptoms were similar between the two groups. CONCLUSIONS: The induction of anesthesia with midazolam-ketamine was thus found to be a valuable method for allergic patients, because the incidence of histamine release, skin reactions and hemodynamic changes in allergic patients were similar to those in non-allergic patients induced by thiamylal and no significant changes were observed in the plasma histamine level after the administration of midazolam-ketamine in spite of the high level of basal plasma histamine.

Adolescent↗
PubMed1999

The basal plasma histamine level and eosinophil count in allergic and non-allergic patients.

OBJECTIVE: The basal plasma histamine level and eosinophil count in the peripheral blood in patients with a history of allergy (allergic patients) were examined and compared with those in patients without any history of allergy (non-allergic patients). SUBJECTS: We preoperatively examined 70 allergic patients and 70 non-allergic patients who were all scheduled to undergo oral surgery. METHODS: The basal plasma histamine level and eosinophil count in the peripheral blood were measured preoperatively. The high performance liquid chromatography (HPLC) post label system was used to measure the plasma histamine level. RESULTS: The mean basal plasma histamine level in non-allergic patients and allergic patients were 0.31 +/- 0.27 ng/ml and 0.47 +/- 0.30 ng/ml, respectively (p < 0.01). The mean eosinophil counts in non-allergic patients and allergic patients were 3.3 +/- 3.0% and 5.3 +/- 3.4%, respectively (p < 0.01). The patients who had asthma, atopic dermatitis or a food-induced allergy showed a high level of basal plasma histamine compared to that in non-allergic patients. The patients with asthma, allergic rhinitis or atopic dermatitis all demonstrated a higher eosinophil count than non-allergic patients. In addition, the correlation between the plasma histamine level and the eosinophil count was statistically significant (p < 0.05). CONCLUSIONS: The allergic patients had both higher basal plasma histamine levels and eosinophil counts than non-allergic patients (p < 0.01).

Adolescent↗
PubMed1999

[ADOC regimen for unresectable advanced thymic cancer].

Between 1996 and 1998, we treated 6 patients with unresectable and advanced thymic cancer (stages IVa and IVb). All received 50 mg/m2 of cisplatin and 40 mg/m2 of doxorubicin intravenously (i.v.) on day 1,0.6 mg/m2 of vincristine i.v. on day 3, and 700 mg/m2 of cyclophosphamide i.v. on day 4; ADOC regimen, respectively at 3-4 week intervals. Four patients obtained a partial response (PR) after ADOC chemotherapy and the overall clinical response rate was 67%. No life-threatening side effects were noted. In 2 patients, cisplatin plus VP-16 chemotherapy failed to demonstrate any benefits prior to the ADOC regimen. Radiotherapy was initiated after the achievement of PR in the other 2 patients. ADOC chemotherapy appears to be an effective treatment for thymic cancer.

Aged↗
PubMed1999

Antitumor effect of vesnarinone on human hepatocellular carcinoma cell lines.

Vesnarinone, a quinolinone derivative, induces apoptosis and differentiation in some tumor cell lines. We examined the antitumor effect of vesnarinone on three human hepatocellular carcinoma (HCC) cell lines. Vesnarinone suppressed the proliferation of all three HCC cell lines, but did not induce apoptosis and differentiation. Vesnarinone has also been reported to inhibit both nucleoside and nucleobase transport. Concomitant administration of vesnarinone and a de novo nucleotide synthesis inhibitor potentiated the growth-inhibitory effect of vesnarinone on HCC cells. Vesnarinone may be useful as a new biochemical modulator of anticancer agents.

Antineoplastic Agents↗
PubMed1998

Cloning and characterization of a mouse homologue (mNthl1) of Escherichia coli endonuclease III.

Endonuclease III (endoIII; nth gene product) of Escherichia coli is known to be a DNA repair enzyme having a relatively broad specificity for damaged pyrimidine bases of DNA. Here, we describe the cloning and characterization of the cDNA and the gene for a mouse homologue (mNthl1/mNth1) of endoIII. The cDNA was cloned from a mouse T-cell cDNA library with a probe prepared by PCR using the library and specific PCR primers synthesized based on the reported information of partial amino acid sequences of bovine NTHL1/NTH1 and of EST Data Bases. The cDNA is 1025 nucleotides long and encodes a protein consisting of 300 amino acids with a predicted molecular mass of 33.6 kDa. The amino acid sequence exhibits significant homologies to those of endoIII and its prokaryotic and eukaryotic homologues. The recombinant mNthl1 with a hexahistidine tag was overexpressed in a nth::cmr nei::Kmr double mutant of E. coli, and purified to apparent homogeneity. The enzyme showed thymine glycol DNA glycosylase, urea DNA glycosylase and AP lyase activities. Northern blot analysis indicated that mNthl1 mRNA is about 1 kb and is expressed ubiquitously. A 15 kb DNA fragment containing the mNthl1 gene was cloned from a mouse genomic library and sequenced. The gene consists of six exons and five introns spanning 6.09 kb. The sequenced 5' flanking region lacks a typical TATA box, but contains a CAAT box and putative binding sites for several transcription factors such as Ets, Sp1, AP-1 and AP-2. The mNthl1 gene was shown to lie immediately adjacent to the tuberous sclerosis 2 (Tsc2) gene in a 5'-to-5' orientation by sequence analysis and was assigned to chromosome 17A3 by in situ hybridization.

Amino Acid Sequence↗
PubMed1998

Simultaneous determination of nicotinic acid and its metabolites in rat urine by micellar electrokinetic chromatography with photodiode array detection.

Nicotinic acid, nicotinamide and their possible metabolites were successfully separated within 17 min by micellar electrokinetic chromatography using 50 mM borate buffer (pH 9.0) containing 150 mM sodium dodecyl sulfate as the running buffer. Calibration curves for all compounds showed good linearity in a range of 5 microg/ml and 250 microg/ml with good correlation. The present method did not require any clean-up procedures and made it possible to determine all metabolites without interference on a photodiode array detector. Urine samples collected from Wistar male rats were analyzed after high-dose oral or intravenous administration of nicotinic acid or nicotinamide. Metabolic pathways of nicotinic acid in male Wistar rats are also discussed.

Animals↗
PubMed1998

Construction of 714 MHz HOM-free accelerating cavities.

A new 'higher-order-mode (HOM)-free' accelerating cavity has been developed which can provide an accelerating voltage of more than 400 kV per cavity at a frequency of 714 MHz. The harmful HOMs in the cavities, which can induce beam instabilities at high beam currents, were heavily damped by using four special waveguide ports and broadband microwave loads. Two cavities of this design were installed in the 1.54 GeV accelerator test facility (ATF) damping ring at KEK, and successfully stored beams. This cavity will also be very useful for synchrotron light sources. The basic design, characteristics of HOMs and construction of this cavity are reported.

Journal Article↗
PubMed1998

Mass screening for lung cancer with mobile spiral computed tomography scanner.

BACKGROUND: The incidence of and mortality from lung cancer have increased steadily. Most lung cancers are not localised when first detected, but early detection is mandatory to improve prognosis. Since curable early cases are hard to visualise with conventional chest radiography, a new diagnostic means must be found. We assessed whether population-based mass screening with a spiral computed tomography scanner could contribute substantially to detection of smaller cancers, and decrease mortality. METHODS: In 1996, we screened in a mobile unit 5483 individuals from the general population of Matsumoto, Japan, aged between 40 years and 74 years who had undergone annual chest radiography (miniature fluorophotography) and cytological assessment of sputum. All participants had a low-dose X-ray spiral computed tomography (CT) scan of the thorax; 3967 also underwent miniature fluorophotography. We compared smokers and non-smokers. Further assessments were done for probably benign but suspicious lesions; suspicion of cancer; and indeterminate small nodules by chest radiography and conventional CT, with additional transbronchial biopsy when possible. Thoracotomy was recommended when it was strongly suspected that the patients had lung cancer. FINDINGS: 19 patients were diagnosed as having lung cancer--14 with suspicion of lung cancer, three with benign but suspicious lesions, and two with indeterminate small nodules. 18 cases were surgically confirmed, and one was clinically diagnosed. The mean size of lesions was 17 mm (range 6-47). In four of 19 patients, lung abnormality was seen on CT and miniature fluorophotography. The lung-cancer detection rate with CT was 0.48%, significantly higher than the 0.03-0.05% for standard mass assessments done previously in the same area. CT missed one case that was found solely on a sputum cytology examination. INTERPRETATION: Our results show that miniature fluorophotography or conventional chest radiography, which have been the main diagnostic techniques for lung cancer, showed few small cancers. CT was more accurate in mass screening for lung cancer and led to early detection and an accurate diagnosis of lung cancer, and should be considered in future health plans.

Adult↗
PubMed1998

Association of high-altitude pulmonary edema with the major histocompatibility complex.

BACKGROUND: A constitutional susceptibility has been suggested in the development of high-altitude pulmonary edema (HAPE) because HAPE generally affects healthy young people, some of whom suffer recurrent episodes. We examined whether immunogenetic susceptibility is present in HAPE-susceptible subjects. METHODS AND RESULTS: The frequencies of human leukocyte antigen (HLA) alleles in 28 male and 2 female subjects with a history of HAPE were compared with those in 100 healthy volunteers. We assayed the HLA-A, -B, -C, -DR, and -DQ antigens serologically. The pulmonary hemodynamics on admission to the hospital and the ventilatory response to hypoxia and hypercapnia were retrospectively examined in 10 of the HAPE-susceptible subjects. HLA-DR6 was positive in 14 (46.7%) of the subjects with HAPE but only 16.0% of the control subjects (P=.0005), and HLA-DQ4 was positive in 12 (40.0%) of the subjects with HAPE but only 10.0% of the control subjects (P=.0001). HLA-DR6 or HLA-DQ4 was positive in 8 (100%) of the subjects with recurrent HAPE. The pulmonary arterial pressure on admission of the HLA-DR6-positive subjects with HAPE was significantly higher than that of the HLA-DR6-negative subjects with HAPE. CONCLUSIONS: There were significant associations of HAPE with HLA-DR6 and HLA-DQ4 and of pulmonary hypertension with HLA-DR6. An immunogenetic susceptibility, which is associated with HLA class II alleles located within the major histocompatibility complex, may underlie the development of HAPE, at least in some of its forms.

Adolescent↗
PubMed1998

Occlusive effects of lactic acid-glycolic acid copolymer membrane on gingival fibroblasts in vitro.

The cell occlusive effects on human gingival fibroblasts of degradable lactic acid-glycolic acid copolymer membranes (noncoated membranes) and membranes coated with a sucrose ester of fatty acid (coated membranes) were studied and compared with those of expanded polytetrafluoroethylene (e-PTFE) membranes. The membranes were immersed in a culture medium periodically for 21 days and interposed into a chemotaxis chamber, and the fibroblasts then were cultured in the chamber for another 7 days. The passage rate of cells through the membranes was calculated and the change in surface structure of each membrane after immersion for 28 days was observed by an environmental scanning electron microscope. The passage rate of coated membranes (3.4+/-2.2%) was significantly lower than that of noncoated (25.7+/-5.1%) at the 28th day whereas the passage rate of e-PTFE membranes was 0.8-1.5%. Many pores were observed on the noncoated membranes before immersion while the coating material covered most of the pores on the coated membranes. The average pore size of the noncoated membranes was larger than that of the coated membranes at day 28. The structure of the e-PTFE membranes underwent no change. The passage rate of the coated membranes was not different from the e-PTFE membranes, suggesting an effect that might be useful for a guided tissue regeneration procedure.

Fibroblasts↗