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Biomedical subjects

J Kobayashi

Publications and source records attributed to J Kobayashi.

At least 289 records · Page 16Linked to original sources

The rabbit pulmonary cytochrome P450 arachidonic acid metabolic pathway: characterization and significance.

Cytochrome P450 metabolizes arachidonic acid to several unique and biologically active compounds in rabbit liver and kidney. Microsomal fractions prepared from rabbit lung homogenates metabolized arachidonic acid through cytochrome P450 pathways, yielding cis-epoxyeicosatrienoic acids (EETs) and their hydration products, vic-dihydroxyeicosatrienoic acids, mid-chain cis-trans conjugated dienols, and 19- and 20-hydroxyeicosatetraenoic acids. Inhibition studies using polyclonal antibodies prepared against purified CYP2B4 demonstrated 100% inhibition of arachidonic acid epoxide formation. Purified CYP2B4, reconstituted in the presence of NADPH-cytochrome P450 reductase and cytochrome b5, metabolized arachidonic acid, producing primarily EETs. EETs were detected in lung homogenate using gas chromatography/mass spectroscopy, providing evidence for the in vivo pulmonary cytochrome P450 epoxidation of arachidonic acid. Chiral analysis of these lung EETs demonstrated a preference for the 14(R),15(S)-, 11(S),12(R)-, and 8(S),9(R)-EET enantiomers. Both EETs and vic-dihydroxyeicosatrienoic acids were detected in bronchoalveolar lavage fluid. At micromolar concentrations, methylated 5,6-EET and 8,9-EET significantly relaxed histamine-contracted guinea pig hilar bronchi in vitro. In contrast, 20-hydroxyeicosatetraenoic acid caused contraction to near maximal tension. We conclude that CYP2B4, an abundant rabbit lung cytochrome P450 enzyme, is the primary constitutive pulmonary arachidonic acid epoxygenase and that these locally produced, biologically active eicosanoids may be involved in maintaining homeostasis within the lung.

Animals↗

Effect of theophylline on the production of interleukin-1 beta, tumor necrosis factor-alpha, and interleukin-8 by human peripheral blood mononuclear cells.

Theophylline is a mild bronchodilator and has significant extrapulmonary effects, but it may also have some anti-inflammatory properties. We investigated the immunological effects of theophylline on peripheral blood mononuclear cells (PBMC), by examining the production of interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), and interleukin 8 (IL-8) when PBMC were stimulated with lipopolysaccharide (LPS) or recombinant human IL-1 beta (rhIL-1 beta). At concentrations > or = 50 micrograms/ml, theophylline suppressed the proliferative activity of PBMC stimulated with phytohemagglutinin (p < 0.05). IL-1 beta production showed 23% suppression by 10 micrograms/ml theophylline (p < 0.05), while the suppression was 26% at 25 micrograms/ml (p < 0.05), 30% at 50 micrograms/ml (p < 0.05), and 33% at 100 micrograms/ml (p < 0.05). TNF-alpha production was suppressed in a dose-dependent manner by theophylline, being decreased by 24% at 10 micrograms/ml (p < 0.05), by 29% at 25 micrograms/ml (p < 0.05), by 41% at 50 micrograms/ml (p < 0.01), and by 54% at 100 micrograms/ml (p < 0.01). IL-8 production, in contrast, was not affected by theophylline. rhIL-1 beta induced IL-8 production in a dose-dependent manner at concentrations of 1-100 units/ml, and theophylline (particularly at concentrations of 50 and 100 micrograms/ml), increased IL-8 production in the presence of rhIL-1 beta. Suppression of the production of IL-1 beta and TNF-alpha by therapeutic levels of theophylline suggested that this drug might have anti-inflammatory and immunosuppressive effects.

Anti-Inflammatory Agents, Non-Steroidal↗

KL-6: a serum marker for interstitial pneumonia.

KL-6 is a mucinous high-molecular weight glycoprotein, expressed on type 2 pneumonocytes, which is reported to be elevated in the serum and bronchoalveolar lavage fluid of patients with interstital pneumonia. A total of 118 samples from 112 patients were measured, including 51 samples with three classes of interstital lung disease and 67 samples with 6 classes of noninterstital lung diseases, in order to clarify whether it was a useful marker of pneumonitis activity. The KL-6 level was significantly higher in patients with pneumonitis (1,187 +/- 689 U/mL; range, 224 to 2,656 U/mL) than in patients without pneumonitis (309 +/- 157 U/mL; range, 123 to 855 U/mL). The KL-6 level was also significantly higher in patients with clinically active pneumonitis (1,497 +/- 560) compared with inactive pneumonitis (441 +/- 276) (p < 0.001). The optimal criterion for separating patients with active pneumonitis from patients without pneumonitis was a KL-6 level of 500 to 700 U/mL according to receiver operating characteristic analysis. These results suggest that KL-6 is a useful marker for the clinical diagnosis of pneumonitis and for the evaluation of disease activity.

Antigens↗

Evaluation of lymph nodes on computed tomography images in epidermoid lung cancer.

This study was undertaken to design the optimal criteria for practical guidelines for lymph node metastasis evaluation in epidermoid lung cancer. Resected lymph nodes (n = 214) were analyzed by preoperative computed tomography (CT) images and postoperative histopathological findings. Definite criteria were defined by efficiency, and possible criteria by receiver operating characteristic (ROC) analysis. Statistical values of highest efficiency in 214 lymph nodes revealed that the minor axis offered the best criteria (minor axis 13 mm; efficiency 93%). ROC curve using the minor axis which showed the highest values of sensitivity and specificity in the optimal criteria (minor axis 9.3 mm; sensitivity 76%, specificity 76%). The criteria of the paratracheal lymph nodes were smaller than those of tracheobronchial and subcarinal nodes. In conclusion, it is desirable to evaluate metastasis of lymph nodes by the minor axis, and criteria should be considered changeable to accommodate the anatomical location in epidermoid lung cancer.

Carcinoma, Squamous Cell↗

Efficacy of stool examination for detection of Strongyloides infection.

To determine the efficacy of stool examination for detection of Strongyloides infection, 1,350 stool samples collected in Japan, Brazil, and Thailand were examined by four different methods (direct fecal smear, formalin-ether concentration. Harada-Mori filter paper culture, and agar plate culture). The newly developed agar plate culture method was highly effective; more than 96% of the positive cases were diagnosed by this method. The coprologic examination, however, was not sensitive enough for detecting chronic infections because more than 40% of the positive cases were overlooked even when persons with proven Strongyloides infection were re-examined several months later without intervening treatment. Therefore, it is essential to examine stool samples repeatedly to achieve a correct diagnosis, and even so, it is important to note that a negative result does not necessarily indicate the unequivocal absence of the infection.

Animals↗

Hantavirus infection among Rattus norvegicus in Japan.

Seroepizootiological study of hantavirus infection among 393 urban rats (Rattus norvegicus) captured in six regions in Japan during the period from 1990 to 1994 was carried out by the indirect fluorescent antibody (IFA) test and Western blot (WB). Fifteen out of 393 (3.8%) rat sera were antibody-positive by IFA, i.e., Tokyo Port (12.8%, 6/47), Shimizu Port (5.7%, 2/35), Otaru Port (1.5%, 1/65) and Nagoya City (3.6%, 6/167). In two other regions, i.e., Kasai Seaside Park and Haneda Airport, rat sera were antibody-negative. One serum with a lower IFA titer, 1:64, from Otaru Port was confirmed to be antibody-positive by WB, while two sera from Shimizu Port (IFA titer, 1:32 and 1:64) were not. In Nagoya City, one out of four sera (IFA titer, 1:32) and one of two sera (IFA titer, 1:64) were also confirmed to be antibody-positive by WB. Continuous hantavirus infection among rats in Tokyo Port, Shimizu Port and Nagoya City and the existence of hantavirus among rats in Otaru Port were demonstrated.

Animals↗

Enhancing student practicum opportunities: the outbreak investigation option.

An outbreak investigation practicum option for graduate students at the University of Washington School of Public Health and Community Medicine has three goals of education, scientific investigation, and exposure to operations of public health agencies. Over a six-year period, 48 students performed 40 outbreak investigations in collaboration with adjunct faculty based in local public health agencies. An outbreak investigation practicum at Yale University had similar goals, but the rapid-response team approach there generally involved one regular faculty member and a team of graduate students. In either program, the level of faculty involvement necessary for outbreak investigations is sustainable only if the faculty value public health practice as part of the school's mission. Since public health students need to acquire many practical skills, a short outbreak investigation practicum experience should not be viewed in isolation, but rather should be one of a variety of practicum offerings available to students at schools of public health.

Curriculum↗

Elevation of tumour markers in serum and bronchoalveolar lavage fluid in pulmonary alveolar proteinosis.

It is unclear whether tumour markers are generally increased in the serum and bronchoalveolar lavage fluid (BALF) of patients with pulmonary alveolar proteinosis (PAP). To clarify this point, levels of tumour markers were measured in the serum and BALF of patients with PAP. Squamous cell carcinoma (SCC) antigen, carcinoembryonic antigen (CEA), and carbohydrate antigens sialyl Lewis (CA 19-9) and sialyl SSEA-1 (SLX) were assayed with radioimmunoassay kits. Cytokeratin 19 fragments (CYFRA) were measured by enzyme-linked immunosorbent assay. Values for the tumour markers in serum, except for SCC, exceeded cut-off values in some PAP patients. Levels of the markers were higher in BALF compared with those in serum, and were significantly elevated in PAP patients compared with control subjects. There was a significant inverse correlation between CA19-9 level in BALF and arterial oxygen tension (PaO2) in PAP patients. A gradual elevation of CA19-9 and SLX was observed in a patient who showed a decrease in PaO2 level during the study period. In the light of these findings, it is possible that levels of tumour markers in BALF, especially levels of CA19-9 and SLX, may reflect the severity of the disease in PAP patients.

Adult↗

[Solitary plasmacytoma of the rib--a case report and review of Japanese literatures].

A 72-year-old woman with solitary plasmacytoma of the right fifth rib was surgically treated. She underwent radical resection of the bony chest wall including the right fifth rib, the ribs above and below the involved rib, the intercostal muscle, and the parietal pleura. Histological finding of the tumor was plasmacytoma of the rib. The type of monoclonal protein was IgG and lamda. She is doing well one year and eleven months after surgery without any signs of recurrence. Solitary plasmacytoma is rare as compared with multiple myeloma. Patients with solitary plasmacytoma originating in the rib have a feasibility of operative indication, and radical treatment is expected to be by adequate surgical resection. Seventeen cases of solitary chest wall plasmacytoma described in the Japanese literature are reviewed.

Adult↗

[A case of pulmonary alveolar proteinosis treated successfully with repeated bronchoalveolar lavage and surfactant replacement therapy].

A 24-year-old woman who had suffered from pulmonary alveolar proteinosis for eight years was admitted to Jichi Medical Hospital with severe pneumonia. She was mechanically ventilated, and her condition markedly improved after repeated bronchoalveolar lavage with surfactant replacement therapy. This method was used because she had been resistant to the conventional unilateral lung lavage method for 12 months. During the bronchoalveolar lavage procedure, she became progressively hypoxic, but recovered immediately after the instillation of surfactant. The combination of bronchoalveolar lavage with surfactant replacement via a fiberoptic bronchoscope may be useful in treating other patients with pulmonary alveolar proteinosis.

Adult↗

Malignant rhabdoid tumor of the breast: a case report.

A 66-year-old woman developed a malignant rhabdoid tumor of the breast, with a tumor doubling time of 10 days. One month after radical mastectomy, there was local recurrence, followed by multiple pulmonary metastases, and the patient died of respiratory failure 5 months after surgery. The gray-white-colored tumor measured 13 x 12 x 10 cm, and its border was well defined. The tumor was composed of diffusely growing round or polygonal cells with vesicular nuclei, prominent nucleoli, and ample cytoplasm containing eosinophilic inclusions. Lymph node involvement was widespread. Both vimentin and keratin were clearly demonstrated by immunohistochemical staining. Ultrastructural studies revealed that the MRT cells contained cytoplasmic whorls of intermediate filaments.

Aged↗

[Results of coronary artery bypass grafting in dialysis patients].

To determine the short- and medium-term results of coronary artery bypass grafting (CABG) in dialysis patients, we analyzed a group of 14 patients with chronic renal failure who underwent CABG between May 1990 and October 1994. Two patients had concomitant valve repair for mitral regurgitation. Hospital mortality was 14% (2 out of 14). These two patients died of ileus due to ischemic colitis and agranulocytosis respectively. There was one late death from stroke. The four significant postoperative complications (morbidity 29%) were composed of two sternal dehiscence, one cardiac tamponade because of bleeding, and one perioperative myocardial infarction. Graft patency rate was 97% (34 out of 35 in 13 patients) within one month. Actuarial survival was 86% at one 1 to 3 years, and 43% at 3 and a half years. This rate is not significantly different from all dialysis patients, but night be better than dialysis patients with coronary artery disease who had not undergone CABG in the previous reports. Left ventricular size is larger in patients who died or who had significant complications in hospital than in patients with uneventful postoperative course. Cardiac arrest time, cardiopulmonary bypass time, chest tube output, and the amount of transfusion might be also related to mortality and morbidity though statistically not significant.

Aged↗

[Evaluation of surgical procedures based on the types of hypertrophied obstructive cardiomyopathy].

The surgical procedures were reviewed based on the types of hypertrophied obstructive cardiomyopathy in 20 patients. The patients were classified in three groups: (1) Asymmetric septal hypertrophy (ASH), (2) Atypical or diffuse concentric hypertrophy (DIF), (3) Mid ventricular obstructive hypertrophy (MID). Among 11 patients with ASH, the ventricular septal myotomy (My) or the myotomy-myectomy (Mye) were performed in 9 patients and MVR was performed in 2 patients. Among 6 patients with DIF, My or Mye were performed in 4 and MVR was performed in 2. All three patients with MID were treated with MVR. The intraventricular systolic pressure gradient greater than 40 mmHg was still existent postoperatively in one ASH patient on whom Mye was performed and in 3 DIF patients on whom My or Mye were performed. The four patients had III degree mitral regurgitation preoperatively and were successfully treated. The postoperative NYHA functional class became II or less in all patients. For ASH, the My was effective in 9 patients except one earlier patient. For DIF, further consideration of surgical procedure might be required. For MID, a MVR is recommended.

Adult↗

A naturally occurring mutation at the second base of codon asparagine 43 in the proposed N-linked glycosylation site of human lipoprotein lipase: in vivo evidence that asparagine 43 is essential for catalysis and secretion.

The patient was a 20-year-old male. His fasting plasma triglyceride and cholesterol levels were 1258 mg/dl and 138 mg/dl, respectively. The lipoprotein lipase (LPL) activity and mass from postheparin plasma of the patient were 0.00 mumol/ml/h (normal range: 5.51 +/- 1.12) and 23 ng/ml (normal range: 220 +/- 42), respectively. DNA sequence analysis of the LPL gene from the patient revealed a homozygous nucleotide change: a A-->G transition at nucleotide position 383, resulting in an amino acid substitution of Ser for Asn43, which is believed to be an N-linked glycosylation site of the LPL mature protein. Expression studies of this mutant LPL cDNA produced an inactive LPL protein which was not secreted into the media.

Adult↗

Effects of chemical modification of membrane thiol groups on hemolysis of human erythrocytes under hydrostatic pressure.

Membrane stability of the human erythrocyte under high pressure was examined by modifying membrane SH-groups with NEM or diamide. Hemolysis at 200 MPa of chemically modified erythrocytes was significantly suppressed by the prolonged incubation of them in a reagent-free medium above 30 degrees C prior to the application of high pressure. However, there was no detectable change regarding membrane phospholipid distribution, CD spectra and SDS-PAGE of membrane proteins, and intracellular K+ concentration during the incubation. On the other hand, the data of protein-spin labeling and SH-group content showed that the SH-groups buried in membrane proteins appeared on their surface by conformational changes of membrane proteins induced during the incubation. The extraction of peripheral proteins from NEM-treated membranes in 0.1 N NaOH was considerably suppressed by the incubation. These results suggest that, upon chemical modification of membrane SH-groups, protein-protein interactions are modulated during prolonged incubation above 30 degrees C so that high pressure-induced hemolysis is suppressed.

Diamide↗

Distribution of vitronectin in plasma and liver tissue: relationship to chronic liver disease.

To clarify the clinical significance of vitronectin, we compared the concentration of plasma vitronectin with serum fibrous markers and liver function test values in patients with chronic liver diseases. We also evaluated the vitronectin content in the liver by means of enzyme-linked immunosorbent assay and the localization of vitronectin in liver tissue with enzyme immunohistochemistry. In chronic liver disease, the concentration of plasma vitronectin was significantly lower than that in healthy controls, being related to the severity of liver disease. The plasma levels of vitronectin showed no correlation to fibrous markers but a significant correlation with those of serum albumin and prothrombin time. On the other hand, the content of vitronectin in liver tissue was significantly increased in chronic liver disease compared with that in normal controls. In the normal liver, vitronectin was observed in the portal area by light microscopy. In chronic hepatitis and cirrhosis, vitronectin was found in the connective tissue around the portal and central veins and in the areas of piecemeal and focal necrosis. These findings suggested that vitronectin is deposited in injured tissue through the process of repair and fibrosis and plays an important role as an adhesive protein. Moreover, the lower levels of plasma vitronectin in chronic liver disease may be due to its decreased synthesis, deposition or both in injured tissue.

Adult↗