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Biomedical subjects

K Kubo

Publications and source records attributed to K Kubo.

At least 289 records · Page 16Linked to original sources

Measurement of erythrocyte volumes in splenectomized horses and sham-operated horses at rest and during maximal exercise.

Erythrocyte volumes of thoroughbred horses were measured. The volumes of splenectomized horses and sham-operated horses 2 hr after injection of 50Cr-tagged erythrocytes (at rest) and during maximal exercise were measured using the non-radioactive isotope 50Cr. Because splenic erythrocytes are released into circulation during exercise, it was estimated that the erythrocyte volumes of the sham-operated horses during maximal exercise are larger than those of the horses at rest. However, the erythrocyte volumes of the sham-operated horses at rest were about equal to those during maximal exercise. In the splenectomized horses, furthermore, erythrocyte volumes at rest and those at exercise were nearly equal. From these results, blood stored in the equine spleen is gradually mixed with circulating blood, and it was clarified that the phenomenon was completed within 2 hr. Although it is basically impossible to measure the circulating erythrocyte volume at rest using the erythrocyte tagged method, we observed that it is possible to measure the total erythrocyte volume using the 50Cr method. Also, the plasma volumes of the splenectomized horses during maximal exercise were found to be slightly smaller than those at rest. On the other hand, in the sham-operated horses, the plasma was decreased by a large quantity after maximal exercise. Therefore, it was suggested that the spleen participates in the phenomenon involving the disappearance of plasma from circulation due to exercise.

Animals↗

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↗

Diffuse pulmonary amyloidosis with monoclonal IgG-kappa gammopathy.

A 62-year-old female with diffuse pulmonary amyloidosis developed abnormal radiographic findings while under observation for hyperimmunoglobulinemia over a ten-year period. Serum immunoglobulin G (IgG) was elevated (4,620 mg/dl), and associated with monoclonal gammopathy (M protein) of the kappa type, but no evident abnormalities were apparent in bone marrow. Chest radiograph and computed tomography showed a diffuse reticulonodular shadow in the bilateral lung. Thoracoscopic lung biopsy specimen revealed depositions of amyloid in the bronchus and pulmonary vessel. We emphasize that diffuse pulmonary amyloidosis should be considered a possible diagnosis in the presence of monoclonal immunoglobulin.

Amyloidosis↗

[Effects of bilateral lung volume reduction surgery in a patient with severe pulmonary emphysema].

A 61-year-old man suffering from severe pulmonary emphysema underwent lung volume reduction surgery on both upper lobes. By one year after surgery functional residual capacity had decreased by 2.5 L and FEV1 had increased by a factor of 2.4. Diaphragm excursion, as assessed by dynamic magnetic resonance imaging, had increased and ventilation and pulmonary gas exchange had improved. Performance on a 6-minute-walk test and exercise tolerance measured on a bicycle ergometer improved, and both peak VE and VO2 increased. Before surgery, pulmonary artery pressure Ppa and pulmonary capillary wedge pressure Pewp during exercise were abnormally high, but 6 months after the operation the increases in Ppa and Pcwp during exercise were markedly reduced.

Chronic Disease↗

[Tumor lysis syndrome after treatment for mediastinal non-Hodgkin's lymphoma].

An 18-year man was admitted to the hospital because of acute dyspnea. Roentgenological examination revealed a large anterior mediastinal tumor. Histologic examination of a specimen from a cervical lymph node yielded a diagnosis of non-Hodgkin's lymphoma of, diffuse, large, T-cell type. Acute respiratory failure and a massive pleural effusion developed, and mechanical ventilation was begun. Chemotherapy with adriamycin, vincristine, cyclophosphamide, and prednisolone resulted in rapid shrinking of the mass. Acute renal failure developed because of hypoperfusion of the kidney caused by acute circulatory failure and the tumor lysis syndrome, and rapid increases in the concentrations of lactate dehydrogenase, creatine phosphokinase, and uric acid in serum after the tumor collapsed. Mediastinal malignant lymphoma often forms a bulky mass, and effective chemotherapy, while it can prolong survival, may also cause the tumor lysis syndrome.

Acute Disease↗

[Tc-99m labeled leukocyte scintigraphy and CT for the evaluation of patients with inflammatory bowel disease].

Seventeen cases (11 patients) of inflammatory bowel disease (IBD) were studied to define the intensity and extent of disease by 99mTc-HMPAO-labeled leukocytes scintigraphy (TLLS), and 10 cases underwent CT examination to evaluate the bowel wall, lymph-nodes, and mesenteric surroundings. Serial TLLS were obtained up to 4 hours and CT was carried out within one week before or after TLLS. The sensitivities of early (1 hour) and delayed (4 hours) TLLS were 91% and 100%, respectively. The respective specificities were 100% and 33%. However, it appeared that mild IBD may yield false negative results in early TLLS while non-specific bowel activity and migration of white cells may cause false positive results in delayed imaging. By setting the diagnostic criteria for labeled leukocyte accumulation on visualization of the small bowel regardless of uptake or activity of the large bowel similar to or greater than lumbar bone marrow, the sensitivity and specificity of delayed TLLS changed to 91% and 83%, respectively. On CT examination, mesenteric lymph-node swelling, periintestinal blurring and dilatation of mesenteric vasa recta were observed in all five patients with active Crohn's disease, while wall thickening and enhancement were seen in four of them. None of the other three cases of inflammatory disease showed positive findings of dilatation of the mesenteric vasa recta, and they revealed relatively low uptake of labeled leukocytes in TLLS. A "scintigram score" was calculated by comparing uptake of tracer in five bowel segments with lumbar bone marrow activity, and a "CT score" was calculated by adding abnormalities of the intestine and mesenteric surroundings. The scintigram score correlated closely with CT score and clinical disease activity. Combined use of CT and TLLS for the evaluation of patients with IBD was an excellent means to obtain the findings of intensity and extent of disease of the bowel wall and mesenteric surroundings and provided useful information in determining the patient management.

Adolescent↗

[Infected emphysematous bullae in a patient with diabetes mellitus].

A 42-year-old woman with diabetes mellitus was admitted to our hospital because of fever, coughing, and dyspnea. Coarse crackles were audible and respiratory sounds were weak in the right lung field. Laboratory examination revealed a high erythrocyte sedimentation rate, a high level of serum C-reactive protein, a high blood sugar level, and hypoxemia. A chest roentgenogram revealed cystic lesions with fluid levels, and an infiltration shadow in the right lung field. A chest computed tomographic scan revealed many cystic lesions with fluid levels and an infiltration shadow. Our diagnosis was infected emphysematous bullae. A tube was inserted percutaneously for drainage and to allow injection of antibiotics into the cystic lesion. The cystic lesion then vanished. Percutaneous drainage and washing with antibiotics can be used to treat infected emphysematous bulla that have thick closed cystic walls.

Adult↗

[Two patients with summer-type hypersensitivity pneumonitis in Nagano Prefecture].

We encountered two patients with summer-type hypersensitivity pneumonitis that developed in Nagano Prefecture. Patient 1 was a 61-year-old man who had worked in warm and humid environments as painter. He was referred to our hospital because of fever, coughing and exertional dyspnea. Respiratory symptoms developed during work but were gone within in few weeks. Patient 2 was a 50-year-old housewife who was admitted to our hospital because of persistent coughing and a low-grade fever. In both patients, chest roentgenograms and computed tomograms showed bilateral, small, nodular and reticular shadows. Examination of a specimen obtained from patient 2 by transbronchial lung biopsy revealed alveolitis. In both patients, bronchoalveolar lavage fluid had low CD4/8 ratios, but in patient 1 the lymphocyte fraction was high and in patient 2 the neutrophil fraction was high. A steroid drug was given to patient 1 because of the patients symptoms and prolonged abnormal roentgenographic findings. Patient 2 reacted positively on a provocation test when returned to her house. Serum from both patients contained antibodies to Trichosporon mucoides and T. asahii. We know of no previous reports of summer-type hypersensitivity pneumonitis that developed in Nagano prefecture.

Alveolitis, Extrinsic Allergic↗

[Pulmonary disease caused by Mycobacterium avium presenting as a solitary cavity with a thickened wall].

A 46-year-old man was admitted for evaluation of a solitary pulmonary cavity in the apey of the left lung. Because two transbronchial biopsies followed by brushing and washing and sputum cytology did not yield any diagnostic findings, the patient was treated with INH, RFP and SM under a tentative diagnosis of pulmonary tuberculosis. The shadow decreased over two months with combination therapy, but increased again after the dose of SM was decreased. We performed a left upper lobectomy to diagnose either multi-drug-resistant pulmonary tuberculosis or lung cancer. Pathological examination of the resected lung revealed epitheloid cell granulomas with areas of caseous necrosis. Smooth chromophoric colonies were isolated on an Ogawa egg medium, and were identified as M. avium by PCR and DDH. A diagnosis of pulmonary M. avium was made. A chest X-ray film taken two years later was normal. Pulmonary M. avium disease developed in this patient, who had no predisposing lung pathologies.

Diagnosis, Differential↗

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↗

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↗

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↗

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↗

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↗