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Biomedical subjects

K Shimokata

Publications and source records attributed to K Shimokata.

287 records · Page 16Linked to original sources
PubMed1976

The effects of cytochalasin and colchicine on interferon production.

The present study was undertaken to investigate the mechanism of interferon production by mouse spleen cells co-cultivated with BHK-HVJ cells, i.e. baby hamster kidney cells persistently infected with the HVJ (or Sendai) strain of para-influenza I virus. Cytochalasin B appears to inhibit an early stage in the process and colchicine a relatively late stage. It is suggested that microfilaments and microtubules may play in important role at an initial stage of interferon production in this system.

Animals↗
PubMed1976

Homologous interference induced by a temperature-sensitive mutant derived from an HVJ (Sendai virus) carrier culture.

Homologous interference between a temperature-sensitive small plaque mutant (HVJ-pB) derived from an HVJ (haemagglutinating virus of Japan - the Sendai strain of parainfluenza I virus) carrier culture of BHK cells and the original wild-type virus (HVJ-W) has been investigated. Prior infection of LLCMK2, HeLa, BHK or mouse L cells with HVJ-pB, both at permissive and non-permissive temperatures, for 24 h resulted in a reduced yield of superinfecting HVJ-W, reflecting a smaller number of cells capable of producing the superinfecting virus. However, HVJ-pB did not interfere with the replication of vesicular stomatitis virus, Sindbis virus or Newcastle disease virus. Interference in this system seems to be due to inhibition of the attachment of superinfecting HVJ-W as a result of intracellular mechanisms operating at a late stage in the replication of the interfering virus. There is also blocking or destruction of cellular receptors by extra-cellular particles of the interfering virus. Protein synthesis coded for by the complete virus genome is required to establish and maintain the interference, and treatment with actinomycin D has no effect on the interference phenomenon.

Adsorption↗
PubMed1976

Interferon-producing capacity of germfree mice.

The general capacity of germfree mouse spleen cells to produce interferon in vitro in response to various stimuli was investigated. The interferon response of germfree mouse spleen cells in vitro, when compared with that of the conventionals, appears to be lower to some inducers. Interferon production in vitro stimulated by hemagglutinating virus of Japan (HVJ) or BHK-HVJ cells (BHK cells persistently infected with HVJ) was apparently suppressed in germfree mouse spleen cells as compared with the corresponding conventionals, whereas no difference of interferon production was observed between germfree and conventional mouse spleen cells in response to Newcastle disease virus, Escherichia coli endotoxin, poly(I:C), and phytohemagglutinin. Although monocontamination with HVJ had no enhancing effect on the interferon-producing ability of germfree mouse spleen cells in response to HVJ, conventionalization for 2 weeks greatly enhanced interferon-producing capacity.

Animals↗
PubMed1976

Pathogenesis of Sendai virus infection in the central nervous system of mice.

The present study was aimed to clarify the pathogenesis of Sendai virus infection to the central nervous system (CNS) of mice. One-to 2-day-old suckling and 4-week-old mice were inoculated intracerebrally with the virus. The virus multiplied higher in suclings than in adults. Immunofluorescent studies in sucklings revealed that the viral antigens appeared initially in ependyma, choroid plexus epithelium, and meninges. Subsequently they spread to subependymal cells and finally were found in neurons of hippocampus for as long as 4 months postinfection. In adults, however, the viral antigens rapidly disappeared in the early stage. Most mice inoculated intracerebrally with Sendai virus appeared healthy, although hydropcephalus developed in a few mice. Virus-specific antibody and interferon production seemed to have no influence on the persistent infection of Sendai virus in the CNS of mice. One of the most significant findings may be that the viral antigens persist in the brain for as long as 4 months in a latent form. This may offer a useful model for the study of latent CNS infection of paramyxoviruses.

Aging↗
PubMed1975

Iterferon induction in mice by BHK cells persistently infected with HVJ.

Intraperitoneal injection into mice of BHK-HVJ cells (BHK cells persistently infected with HVJ) induced considerable amounts of circulating interferon. Sonication of BHK-HVJ cells almost totally abolished their interferon inducing capacities. This result suggests that a certain native organized structure of virus infected cells might be essential for production of interferon in this system, as is suggested in the in vitro sytem.

Animals↗
PubMed1975

Temperature-sensitive virus derived from BHK cells persistently infected with HVJ (Sendai virus).

BHK-HVJ cells, a cell line of baby hamster kidney cells persistantly infected with HVJ (Sendai virus), started to produce infectious virus by shifting down the incubation temperature from 38 to 32 C. The virus derived from BHK-HVJ cells, designated as HJV-pB, was effectively neutralized with antibody against wild-type virus (HVJ-W) which was used for the establishment of BHK-HVJ cells. HVJ-pB replicated in eggs at 32 C, but not at 38 C, while HVJ-W grew equally well at both temperatures. When BHK cells infected with HVJ-PB were incubated at 38 C, production of infectious virus, hemagglutinin, and neuraminidase was markedly restrained, whereas a considerable amount of viral nucleocapisid and envelope antigens was detected in the cells by complement fixation tests. These viral activities became detectable immediately after temperature shift-down from 38 to 32 C even at the later stage of infection. HVJ-pB was indistinguishable from HJV-W with respect to particle size, density, and morphological characteristics, but appeared to possess a higher neuraminidase activity and was inactivated more rapidly at 50 C than HVJ-W. HVJ-pB was less cytocidal and could easily cause latent infection in BHK and mouse L cells.

Animals↗
PubMedDate not supplied

Estimation of the area under the concentration-versus-time curve of carboplatin following irinotecan using a limited sampling model.

OBJECTIVES: The aim of this study was to develop limited sampling models for estimating the area under the concentration-versus-time curve (AUC) of carboplatin. METHODS: Based on pharmacokinetic analyses of 14 patients who received 300 mg x m2 of carboplatin over a 90-min infusion following irinotecan, we developed limited sampling models with stepwise multiple linear regression analysis. We validated these models to be unbiased and precise using pharmacokinetic data of a second group of 14 patients. We also compared the observed and the predicted AUC in the patients using Calvert's formula with the patients' renal function. RESULTS: We developed the following models: AUC (mg x ml(-1) x min) = 0.784 x C4 + 1.30 (r2=0.930) and AUC=0.100 x C0.25 + 0.597 x C4 + 0.140 (r=0.992), where C0.25 and C4 denote unbound plasma concentrations (microg x ml(-1)) of carboplatin at 0.25 h and 4 h after the end of infusion, respectively. These models were validated to be unbiased and precise: a mean prediction error (MPE) with standard deviation (SD) = 2.41 (9.45)% and a root mean squared error (RMSE) = 9.42% for the one-sample model, and MPE with (SD) = 1.22 (5.56)% and RMSE = 5.49% for the two-sample model. We also calculated predicted AUC in the patients using Calvert's formula: MPE with (SD)= -5.87 (21.5)% and RMSE = 21.5%. CONCLUSIONS: These estimations were, as expected, more accurate than the prediction using Calvert's formula based on patients' renal function. The result of this study confirmed the idea that the pharmacokinetic parameters derived from limited sampling models would be more suitable for pharmacokinetic analysis of carboplatin than those obtained using Calvert's formula.

Adult↗
PubMedDate not supplied

Inhibition of influenza A virus replication by a kanamycin derivative.

We studied the antiviral activity and the mechanism of action of a new antiviral agent and kanamycin derivative, 1-N-eicosanoyl-3"-N-trifluoroacetyl kanamycin A (ETKA), against influenza A virus. From yield reduction assays with VERO cells, ETKA showed a significant antiviral activity with negligible cytotoxic effect. In the presence of 20 micrograms/ml of ETKA at which VERO cell growth was not inhibited, virus titer was suppressed to 11.2% of control, and at 100 micrograms/ml virus production was suppressed to more than 99%. ETKA markedly inhibited viral protein synthesis when cells were pretreated with the drug before infection, but there was no inhibition when the drug was added 15 min post-infection. ETKA did not inhibit virus adsorption and penetration. Nor did it affect the activity of viral RNA polymerase in vitro. We found that the drug had a direct inactivating effect on influenza A virus under acidic conditions. These results suggest that ETKA exerts its antiviral action mainly in the early stage, prior to uncoating by direct inactivation of the virus due to the acidic environment of the endocytic vesicle. Aerosol treatment with the drug protected mice against a lethal influenza A virus infection.

Animals↗
PubMedDate not supplied

Oral adsorbent AST-120 ameliorates interstitial fibrosis and transforming growth factor-beta(1) expression in spontaneously diabetic (OLETF) rats.

Diabetic nephropathy is a common cause of end-stage renal disease. The administration of an oral adsorbent, AST-120, prevents the progression of chronic renal failure in uremic rats and undialyzed uremic patients. This study was designed to determine if AST-120 slows the progression of diabetic nephropathy using Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of non-insulin-dependent diabetic mellitus. At 21 weeks of age the OLETF rats were divided into 2 groups: AST-120-administered OLETF rats (n = 7), and control OLETF rats (n = 7). LETO rats, which are genetically similar to the OLETF rats but not diabetic, were also included. After the oral administration of AST-120 for 65 weeks, renal function and pathological changes were investigated in the 3 groups. The administration of AST-120 to the OLETF rats attenuated the progression of glomerular sclerosis, interstitial fibrosis, tubular injury as well as renal dysfunction, and reduced the serum and urinary levels of indoxyl sulfate. Furthermore, AST-120 administration reduced the interstitial expression of transforming growth factor (TGF)-beta(1) and tissue inhibitor of metalloproteinase (TIMP)-1, as well as interstitial infiltration of macrophages. The TGF-beta(1)-stained interstitial area showed positive correlations with the interstitial fibrosis area, the number of TIMP-1-positive cells, and the number of macrophages, and showed a negative correlation with creatinine clearance. In conclusion, AST-120 reduced the interstitial expression of TGF-beta(1) and TIMP-1, and the interstitial infiltration of macrophages, and ameliorates the progression of diabetic nephropathy in OLETF rats.

Administration, Oral↗
PubMedDate not supplied

Enzyme-linked immunosorbent assay for the differential diagnosis of pulmonary tuberculosis and pulmonary diseases due to Mycobacterium avium-intracellulare complex.

We studied the usefulness of antibody estimation by the enzyme-linked immunosorbent assay (ELISA) technique in the differential diagnosis of pulmonary mycobacterial diseases. Sera from patients with active pulmonary diseases caused by Mycobacterium tuberculosis (n = 42) or Mycobacterium avium-intracellulare complex (MAI) (n = 26) and from healthy controls (n = 75) were assayed for IgG and IgA antibody titers to antigen of M. tuberculosis and MAI. The IgG and IgA antibody titers to M. tuberculosis antigen were significantly higher in patients with mycobacterial diseases than in healthy controls, however, there was no significant difference between patients with pulmonary tuberculosis and those with pulmonary diseases due to M. avium-intracellulare complex (MAID). The IgG and IgA antibody titers to MAI antigen in MAID patients were significantly higher than in healthy controls and in patients with pulmonary tuberculosis. ELISA for IgG antibody against M. tuberculosis antigen had a sensitivity of 54.8% and a specificity of 73.1% in the differential diagnosis of pulmonary tuberculosis. The estimation of the IgA antibody against MAI antigen using ELISA is more useful for the differential diagnosis of MAID because of its sensitivity (69.2%) and specificity (90.5%).

Adult↗
PubMedDate not supplied

Cytomegalovirus-induced gastritis in a bone marrow transplant patient.

Cytomegalovirus (CMV)-induced interstitial pneumonitis is a well-known lethal complication in bone marrow recipients. CMV is also known to cause gastroenteritis. We report the first case of a bone marrow recipient who developed CMV-induced gastritis which is verified both histologically and virologically. The gastritis preceded the interstitial pneumonitis which was detected in an early stage and was successfully treated. We propose that bone marrow recipients who show signs and symptoms of gastritis undergo an endoscopic examination, and that biopsied specimens should be scrutinized for CMV by both histological examination and culture investigation.

Bone Marrow Transplantation↗
PubMedDate not supplied

Cytomegalovirus pneumonitis occurring after allogeneic bone marrow transplantation: a study of 106 recipients.

We have followed 106 recipients of allogeneic bone marrow transplantation (BMT), and observed 47 episodes of interstitial pneumonitis (IP) in 37 patients. Cytomegalovirus (CMV) pneumonitis was seen in 18 episodes in 18 patients, of whom 10 patients were diagnosed by bronchoalveolar lavage (BAL), 7 patients by autopsy, and 1 patient by sputum culture. There was one varicella-zoster virus pneumonitis diagnosed by autopsy. However, we could find no apparent etiology of pneumonitis in the other 18 patients. The median interval between BMT and episodes of IP was 74 days (range, 23-578 days) for CMV pneumonitis, and 180 days (range, 41-428 days) for idiopathic pneumonitis (p less than 0.05). BAL was more sensitive than transbronchial lung biopsy in the diagnosis of CMV pneumonitis, and CD4/CD8 ratio in BAL fluid was inverted in all episodes of CMV pneumonitis. Computed tomography (CT) scans were performed in 31 episodes in 26 patients, and all scans revealed abnormalities. CT scans were more sensitive than routine chest X-rays against micro- or small-nodular patterns, air bronchogram, and air alveologram (p less than 0.05). CT scan and arterial blood gas analysis were most useful and necessary in approaching the problem of pneumonitis in allogeneic marrow transplant patients. Based on these findings, when CMV pneumonitis is suspected, it is recommended to perform BAL for the final diagnosis of CMV pneumonitis.

Adolescent↗
PubMedDate not supplied

Primary chondrosarcoma of the lung--a case report with immunohistochemical study.

A case of primary chondrosarcoma of the lung is presented. The tumor, located in the medial segment of the right lower lobe, was successfully resected surgically. Clinical survey did not reveal any primary lesion elsewhere. The tumor consisted of myxomatous, chondromatous, and fibrous lesions. Immunohistochemical study revealed that tumor cells were positive for S-100 protein and vimentin, and negative for other antisera which characterize epithelial tumors. With these clinical, histological, and immunohistochemical studies we diagnosed the tumor as a primary chondrosarcoma of the lung.

Aged↗