Biomedical subjects

K Shimokata

Publications and source records attributed to K Shimokata.

At least 19 recordsLinked to original sources

PubMed1992

Expression of factor X and its significance for the determination of paramyxovirus tropism in the chick embryo.

Enveloped animal viruses usually possess a surface glycoprotein which mediates fusion between the viral envelope and host cell membrane, hence enabling the initiation of infection, and its biosynthesis often involves post-translational endoproteolytic activation of the inactive precursor by a host cell protease(s). Therefore, the protease distribution in the host must be critical for determining the viral tropism. We previously isolated from chick embryo a cogent candidate endoprotease of this kind for paramyxovirus infection, and demonstrated its identity with factor X (FX), a vitamin K-dependent serine protease in the prothrombin family which, in general, is synthesized in the liver and circulates as one of the plasma proteases essential for blood clotting. Here, we examined FX expression with specific cDNA and antibody probes in a series of embryonic tissues. Many tissues other than the liver expressed the specific mRNA but, in most instances, the translation products remained inactive zymogen forms. The enzymatically active FXa was detectable only in the allantoic fluid and amniotic fluid, and virus spreading was strictly confined to the tissues in direct contact with these FXa-containing fluids. Thus, the ectopically expressed FXa is probably the major host determinant of paramyxovirus tropism in ovo.

Animals↗

PubMed1992

Pathogenesis of cytomegalovirus-associated pneumonitis in ICR mice: possible involvement of superoxide radicals.

We have studied the pathogenesis of murine cytomegalovirus (MCMV) pneumonitis in immunocompetent ICR mice and in mice treated with cyclophosphamide (CP). Intranasal infection of immunocompetent mice with MCMV resulted in transient and self-limited pulmonary lesions. When mice were given 200 mg/kg of CP one day before virus infection, transient splenic atrophy and subsequent splenic hypertrophy were induced, and the lesions in the lung were markedly augmented in their number and size although there was no significant enhancement of the virus growth. The augmentation coincided with the period of splenic hypertrophy. A marked increase in the number of pulmonary lesions was also induced in mice given 100 mg/kg of CP every 4 days following the initial dose of 200 mg/kg. In these mice, however, continuous splenic atrophy and augmented replication of MCMV in the lung were observed. When the activity of xanthine oxidase (XO) in lung tissue homogenates was measured, the activity was found to significantly increase after intranasal infection with MCMV irrespective of CP administration and there was a good correlation between the elevation of XO activity and the degree of pathological changes in the lung. In addition, we found that the administration of allopurinol, a specific inhibitor of XO and superoxide dismutase, a superoxide radical scavenger, reduced the number of the pulmonary lesions. These results suggest that superoxide radicals are involved in the pathogenesis of MCMV-associated pneumonitis in ICR mice.

Allopurinol↗

PubMed1992

On the association of human beta 2 microglobulin with cell culture-grown human cytomegalovirus (HCMV).

We studied the production of human beta 2 microglobulin (beta 2m) in mock-infected or human cytomegalovirus (HCMV) infected human embryonic lung fibroblasts (HEL) and the association of human beta 2m with HCMV virions. Titration of beta 2m by two-step sandwich enzyme immunoassay revealed that HEL released considerable amounts of human beta 2m into the culture medium and that the production of beta 2m was significantly enhanced by HCMV infection. The concentration of human beta 2m in the culture medium of HCMV-infected HEL reached 500 to 600 ng/ml, which corresponded to 7- to 12-fold of levels found in healthy adult urine. Immunoprecipitation assays showed that HEL-grown HCMV bound a significant amount of endogenous beta 2m, but the viruses were efficiently neutralized by either human hyperimmune anti-HCMV globulin or anti-HCMV monoclonal antibody even when treated with a large amount of human beta 2m or with dialysed urine. Thus it seems unlikely that the binding of beta 2m by HCMV is involved in masking the viral antigenic site necessary for neutralization.

Cells, Cultured↗

PubMed1992

Small caliber catheter drainage for spontaneous pneumothorax.

Excellent results have been reported after small caliber catheters were used for iatrogenic pneumothoraces. However, the value of using such catheters for spontaneous pneumothoraces is not clear. The purpose of this study, therefore, is to examine the efficacy of small caliber catheters in managing spontaneous pneumothoraces. Seventy six episodes of spontaneous pneumothorax were treated using a small caliber catheter (No. 5.5 or 7.0 French) connected to a Heimlich valve. All catheters were inserted by physicians. The treatment was considered successful when there was no air leakage and little or no residual pneumothorax. Before the lungs were fully expanded, four patients had died and one had refused to comply with further treatment. The remaining 71 episodes of pneumothoraces were evaluated for efficacy. The treatment was successful in 60 patients (84.5%) and ineffective in the remaining 11. The conventional large caliber tube was inserted in 10 of the 11 failures, but they were successful in only six. No major complications resulting from catheter insertion occurred, and no catheters became occluded. The catheter was easy to insert, and the scar that remained after removal of the catheter was very small. Not only are small caliber catheters effective for managing spontaneous pneumothoraces, they are the initial treatment of choice.

Catheterization↗

PubMed1992

Bacteriostatic and bactericidal activity of antituberculosis drugs against Mycobacterium tuberculosis, Mycobacterium avium-Mycobacterium intracellulare complex and Mycobacterium kansasii in different growth phases.

Bacteriostatic and bactericidal activities of rifampicin, isoniazid, streptomycin, enviomycin and ethambutol against Mycobacterium tuberculosis, Mycobacterium avium--M. intracellulare complex and Mycobacterium kansasii were studied in different growth phases. Bacteriostatic activities of the drugs were similar in different growth phases, except isoniazid. M. tuberculosis was much less susceptible to isoniazid in the lag phase than in the log and the stationary phases. In contrast, bactericidal activity was influenced by the growth phase. M. tuberculosis was killed by isoniazid, streptomycin and rifampicin. The bactericidal activity of isoniazid was strongest. The bactericidal activity of isoniazid and streptomycin was most marked in the log phase. M. avium complex and M. kansasii resisted the bactericidal activity, but some strains of M. avium complex were killed by streptomycin and enviomycin, and the activities of these two drugs were most marked in the lag phase.

Antitubercular Agents↗

PubMed1992

Complex intrachromosomal rearrangement in the process of amplification of the L-myc gene in small-cell lung cancer.

The L-myc gene was first isolated from a human small-cell lung cancer (SCLC) cell line on the basis of its amplification and sequence similarity to c-myc and N-myc. A new mechanism of L-myc activation which results from the production of rlf-L-myc fusion protein was recently reported. On the basis of our earlier observation of a rearrangement involving amplified L-myc in an SCLC cell line, ACC-LC-49, we decided to investigate this rearrangement in detail along with the structure of L-myc amplification units in five additional SCLC cell lines. We report here the identification of a novel genomic region, termed jal, which is distinct from rlf and is juxtaposed to and amplified with L-myc during the process of DNA amplification of the region encompassing L-myc. Long-range analysis using pulsed-field gel electrophoresis revealed that the amplified L-myc locus is involved in highly complex intrachromosomal rearrangements with jal and/or rlf. Our results also suggest that the simultaneous presence of rearrangements both in rlf intron 1 and in regions immediately upstream of L-myc may be necessary for the expression of rlf-L-myc chimeric transcripts.

Carcinoma, Small Cell↗

PubMed1992

Umbilical metastasis from small cell carcinoma of the lung.

Umbilical metastases have been almost exclusively reported in patients with adenocarcinomas of intra-abdominal organs. We present a case of small cell carcinoma of the lung with umbilical metastasis that was confirmed by biopsy. To our knowledge, this is the first reported case of umbilical metastasis from small cell lung cancer.

Aged↗

PubMed1992

Relationship between gallium 67 citrate scanning and transferrin receptor expression in lung diseases.

The uptake of gallium 67 (67Ga) into cells is postulated to be through transferrin receptors (TFR) of 67Ga combined with transferrin. We studied the relationship between gallium 67 citrate scanning (67Ga scan) and immunohistochemical TFR expression in lungs of nine patients with lung cancer and eight patients with diffuse interstitial lung diseases. We found that lung cancer tissues of positive 67Ga scan expressed TFR, but those of a negative scan did not. In all of the five patients with idiopathic pulmonary fibrosis (IPF), TFR were expressed on the membrane of alveolar macrophages that formed clusters. However, TFR were not expressed in lymphocytes, neutrophils, type 2 alveolar epithelial cells, and endothelial cells. In two patients with sarcoidosis and a patient with pneumoconiosis, TFR were expressed positively only on the membrane of foamy alveolar macrophages and epithelioid cells of granuloma. These findings suggest that 67Ga-citrate initially combines with transferrin in the blood and then the complex is incorporated into cells through TFR. Therefore, 67Ga scan could be positive when cells have TFR and one should be able to observe cancer cells, clusters of alveolar macrophages, and epithelioid cells through the imaging of 67Ga scan in lung cancer and diffuse interstitial lung diseases.

Citrates↗

PubMed1992

Chest roentgenogram classification and clinical parameters in patients with active pulmonary tuberculosis.

The relationship between the clinical parameters and chest film appearance was studied in patients with active pulmonary tuberculosis. Patients with extended disease were often malnourished and had weak tuberculin reaction accompanied by lymphopenia. They excreted a large amount of mycobacterial bacilli and a longer period was required for negative conversion of sputum culture. We confirmed that the criteria for chest roentgenogram classification established by the Japanese Society for Tuberculosis ("Gakkai Classification") is useful in the estimation of the risk of infection and the prognosis of tuberculosis patients.

Adolescent↗

PubMed1992

Diffuse pulmonary alveolar hemorrhage in acute promyelocytic leukemia.

A 60-year-old male with acute promyelocytic leukemia demonstrated bilateral diffuse air-space consolidation on chest X-ray. An autopsy on the next day revealed pure pulmonary alveolar hemorrhage without leukemic infiltration or inflammation. Disseminated intravascular coagulation was confirmed microscopically. In severe hemorrhagic diathesis and leukopenia, it is impossible to distinguish pulmonary hemorrhage from pneumonia by X-ray alone. Bronchalveolar lavage may be the only possible diagnostic approach.

Bronchoalveolar Lavage Fluid↗

PubMed1992

Immunosuppressive activity induced by nitric oxide in culture supernatant of activated rat alveolar macrophages.

Alveolar macrophages (AM) from normal rats had immunosuppressive activity to mitogen-induced proliferative responses of splenic lymphocytes. We studied the mechanism and the implication of the nitric oxide synthetase pathway in AM-mediated suppression of concanavalin A (Con A)-induced lymphocyte proliferation. The culture supernatant from AM cultures alone did not have immunosuppressive activity to Con A-induced proliferative responses of non-adherent spleen cells (n-ad SC), but the culture supernatant from co-culture of AM and autologous n-ad SC had this activity. Con A-pulsed AM also liberated the immunosuppressive factor. When AM and autologous n-ad SC were cultured separately under the condition that medium could freely communicate, the culture supernatant did not suppress the Con A-induced proliferative response of n-ad SC. This indicated that the immunosuppressive factor was liberated when AM was activated by cell-to-cell contact with n-ad SC. Further, we examined the immunosuppressive activity of the culture supernatant of co-culture of AM and autologous n-ad SC to Con A-induced responses of allogeneic n-ad SC and xenogeneic murine n-ad SC, and allogeneic mixed leucocyte reaction, and found that this culture supernatant could suppress all these proliferative responses. Nitrate (NO2-) synthesis was markedly augmented in the culture supernatants of Con A-pulsed AM and co-culture of AM and n-ad SC. NG-monomethyl-L-arginine (MMA), a specific competitive inhibitor of the nitric oxide synthetase pathway (NOSP), extinguished both NO2- synthesis by AM and AM-mediated immunosuppressive activity. These data suggest that NOSP was important in AM-mediated suppression of Con A-induced lymphocyte proliferation.

Animals↗

PubMed1992

[Manipulation, premedication, and chemoprophylaxis for fiberoptic bronchoscopy].

Manipulation, premedication, and chemoprophylaxis for fiberoptic bronchoscopy vary among institutions. We analyzed the actual conditions by means of a questionnaire distributed to 29 institutions. With regard to premedication, a combination of atropine sulfate and sedatives, such as hydroxyzine hydrochloride, was the most common method. In cases with heart disease and elderly subjects, a lower dosage or omission of atropine was common. In cases with marked anxiety, narcotics were prescribed. Bronchofiberscopic examination was performed under local anesthesia at all institutions. Lidocaine 4% was used for anesthesia of the orolarynx, and 2% was used for the tracheobronchus. For prophylaxis of infection, 19 of 29 institutions prescribed antibiotics routinely or under certain circumstances. ECG was used in 14 institutions, and percutaneous oxygen monitoring in 5 institutions. It is concluded that the manipulation and premedication for fiberoptic bronchoscopy vary between institutions. It is necessary to determine more efficacious and safer methods for fiberoptic bronchoscopy.

Anesthesia, Local↗

PubMed1992

[An autopsy case of massive pulmonary hemorrhage in systemic lupus erythematosus].

A 60-year-old female was admitted to our hospital because of respiratory failure. She was diagnosed as having systemic lupus erythematosus (SLE) in 1971 and had been treated with low-dose oral corticosteroids for 13 years. She developed cough, fever and anemia several days after oral corticosteroids were tapered. Initially, she had no complications such as congestive heart failure, renal failure or bleeding tendency. Respiratory failure progressed without any response to antibiotic therapy. Chest roentgenogram showed bilateral diffuse infiltrates and air bronchograms. There was no improvement even with steroid pulse therapy, and she died of multiple organ failure. Autopsy revealed massive intra-alveolar hemorrhage and interstitial pneumonitis. Deposition of immunoglobulins in the lung was not seen. To our knowledge, this is the 11th reported case of SLE associated with pulmonary hemorrhage in Japan.

Female↗

PubMed1992

[Prophylactic use of antibiotics for fever following fiberoptic bronchoscopy and bronchography].

To evaluate the effect of bacampicillin hydrochloride on fever following fiberoptic bronchoscopy and bronchography, we conducted multi-institutional randomized study. In bronchographic examinations, the rise of body temperatures in the bacampicillin group (0.82 +/- 0.13 degrees C: mean +/- SE) was significantly smaller than that in the control group (1.39 +/- 0.25 degrees C) on the second day of examination. Bacterial infection may contribute to the rise of temperature on the day following bronchography, but no pneumonia or sepsis was observed. There was no differences in the rise of body temperature on the first, third or fourth day. In fiberoptic bronchoscopic examinations, there was no difference between the two groups. We conclude that there is no clinical indication of the value of prophylactic use of antibiotics in either fiberoptic bronchoscopy or bronchography.

Adult↗

PubMed1992

Quantitative analysis of antigen for the induction of tolerance in carcinoembryonic antigen transgenic mice.

In order to analyse the amounts of antigen in the thymus for the induction of tolerance, several carcinoembryonic antigen (CEA) transgenic lines were established which expressed human CEA antigen with different amounts. The chimeric KSN nude mice transplanted with the thymus of the B601 line (in which CEA mRNA and CEA protein could be detected in various tissues) to kidney capsule showed tolerance to human CEA. On the other hand, the chimeric KSN nude mice transplanted with the thymus of the B602 or BC60 line (in which neither CEA mRNA nor CEA protein could be detected by Northern blot analysis and flow cytometry analysis) or normal C57BL/6 (B6) did not develop the tolerance to human CEA. However, the chimeric KSN nude mice transplanted simultaneously with thymus of the B6 and spleen of the B601 line became tolerant to human CEA antigen. In the case of systemic immunization with cells which had CEA antigen, the B601 line was tolerant to human CEA. Surprisingly, the B602 and BC60 lines were also tolerant to CEA molecule. These results indicate that not only the antigen present in the thymus but also the antigen which flows from the peripheral organs to the thymus may be necessary for the induction of CEA tolerance.

Animals↗

PubMed1991

Preferential expression of c-kit protooncogene transcripts in small cell lung cancer.

As an initial step to understand rapid growth of small cell lung cancer (SCLC), a complementary DNA library prepared from a SCLC cell line was screened with viral oncogene probes encoding protein-tyrosine kinases, which are known to play an important role in regulation of cell growth. Fifteen clones hybridizing with v-fms probe were isolated, and, by partial sequence analysis, four of them were identified to be c-kit protooncogenes. Northern blot study demonstrated that most of the SCLC tumors and cell lines expressed c-kit transcripts, while non-SCLC tumors and cell lines did not. Neither amplification nor rearrangement of the c-kit gene was demonstrated in SCLC cell lines by Southern blot analysis, however. Our results suggested that c-kit expression in SCLC reflects the unique biological nature of the tumor cells different from non-SCLC and further suggested that the c-kit product may participate in autocrine or paracrine stimulation of SCLC growth.

Base Sequence↗

PubMed1991

A possible site of in vivo action of cyclosporin A for transplantation immunity: comparative study with cyclophosphamide.

The immunosuppressive mechanisms of cyclosporin A (CsA) and cyclophosphamide (CPM) in vivo were studied by measuring the transplantation immunity for second set rejection of an allogeneic ascites tumor. The transplantation immunity in our assay system was mediated primarily by allospecific cytotoxic T lymphocytes (CTL). Our results showed that both CsA and CPM did not affect the process of inducing the immunity, but they inhibited the effector phase of that transplant immunity. The experiments using 51Cr-release assay in vitro on peritoneal exudate cells as effector cells showed that the effector phase of the transplantation immunity in vivo involved the maturation from immunological memory CTL-precursor cells to effector CTL with clonal expansion. Further, adoptive cell transfer experiments showed that CsA did not eliminate the immunological memory CTL nor induce the suppressor cells in donor mice. All the data suggested that the maturation of memory CTL precursor cells to effector CTL was inhibited by CsA which would block lymphokine production even in vivo, whereas CPM eliminated the CPM-sensitive memory CTL precursor cells. The findings that CsA and CPM act on the different sites of CTL maturation support the possibility of effectiveness of the combination therapy of the two agents for controlling the transplantation immunity.

Animals↗

PubMed1991

Establishment and characterisation of human carcinoembryonic antigen transgenic mice.

We have produced human CEA transgenic mice which were found to express CEA mRNA in all tissues. By immunoblot analysis using anti-CEA polyclonal antibody, we also detected CEA protein in all tissues. However, the molecular size of CEA in the brain was different from that in other tissues, although the mRNA size was same and no deletion nor rearrangement was detected at the DNA level. Immunohistochemical analysis of the lung and the colon showed that the expression sites were the bronchial epithelial cells of the lung and the columnar epithelial cells of the colon. Interestingly, the expression of CEA protein in the transgenic mice was polarised to the luminal side of epithelial cells similar to the normal CEA expression in human tissues. We also detected cell surface expression of human CEA on thymocytes and spleen cells and CEA expression was greatly reduced by the phosphatidylinositol-specific phospholipase C (PI-PLC) treatment.

Animals↗