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Biomedical subjects

N Ishida

Publications and source records attributed to N Ishida.

At least 451 records · Page 25Linked to original sources

Experimental myocarditis induced in mice by infection with influenza A2 virus.

A mouse model was established for the study of acute myocarditis that occurs during influenza infection. Challenge with more than 10 LD50 of mouse-adapted influenza A2 virus (H2N2) induced myocarditis macroscopically discernible as white, irregularly shaped lesions which were shown by histological examination to consist of necrotic myofibers surrounded by infiltrating mononuclear inflammatory cells. After challenge with 10 LD50 of the virus, macroscopic myocarditis was found to advance in a progressive manner up to the 7th day, while the virus titer in the heart reached its peak on the 2nd day and began to decrease on the 5th day of infection. However, development of myocarditis was significantly suppressed in mice which were irradiated with 400 R of X-rays before infection. In addition, myocarditis did not develop in congenitally athymic nude mice. These data indicate that myocarditis was not brought about by viral action directly, but that it was mediated by some function of the host against viral invasion, which was abolished by X-irradiation. The data also suggest that T cells played a key role in the development of myocarditis.

Animals↗

Interferon-inducing activity of an immunotherapeutic anticancer agent, SSM, prepared from Mycobacterium tuberculosis strain Aoyama B.

The interferon-inducing capacity of arabinomannan-lipid preparation (SSM) extracted from Mycobacterium tuberculosis Aoyama B in both BCG-sensitized and unsensitized mice was studied in comparison with that of purified protein derivative (PPD) prepared from the same tubercle bacillus. Although it is known that PPD cannot stimulate interferon production in BCG-unsensitized mice, interferon activity was found in sera of both groups of mice after intravenous injection of SSM at a dose of 5 mg/kg. The maximum titer was detected 5 hr after injection. The interferon induced by SSM in both groups of mice shared certain physicochemical properties with the immune interferon induced by PPD in BCG-sensitized mice. In BCG-unsensitized mice, interferon induction by SSM was markedly inhibited by pretreatment with trypan blue and carrageenan, whereas it was not depressed in BCG-sensitized mice given the same treatment or when interferon was induced by PPD. In addition, induction of interferon in BCG-sensitized mice by SSM and PPD and in unsensitized mice by SSM was completely abrogated by pretreatment with hydrocortisone acetate and whole-body x-irradiation (700 R). These results suggest that in BCG-unsensitized mice macrophages, in addition to X-ray or hydrocortisone-sensitive cells, may be required for interferon induction by SSM.

Animals↗

Lactate dehydrogenase-elevating agent is responsible for interferon induction and enhancement of natural killer cell activity by inoculation of Ehrlich ascites carcinoma cells into mice.

Inoculation of Ehrlich ascites carcinoma cells (EAC) into the peritoneal cavities of outbred ddY mice induced interferon (IFN) in the circulation. The maximum titer (1,280 U) was obtained at 24 hr after inoculation. This induced IFN had the characteristics of type I IFN, i.e., stability at pH2 and lability at 56 C. An increase in natural killer cell (NK) activity was also observed for the first 3 days after inoculation. In addition, plasma lactate dehydrogenase (LDH) activity was elevated in these mice. Inoculation of ascitic fluid or serum of EAC-bearing mice into normal mice increased plasma LDH activity six- to sevenfold over normal levels and elevated activities persisted throughout the life of the mice. These results suggest that the LDH-elevating agent was responsible for IFN induction and for enhancing NK activity. Because lactate dehydrogenase-elevating virus (LDV) can be eliminated from tumor cells by passage in vitro, we attempted to grow EAC in tissue culture for several months and re-examined whether the inoculation of such cells could elevate plasma LDH activity induce IFN and enhance NK activity. The results showed that inoculation of the passaged cells had no effect on these activities in normal mice. Therefore, we concluded that the IFN inducer was LDV which contaminated the EAC and then enhanced the NK activity. N-tropic murine leukemia virus also contaminated EAC, but this virus was not responsible because cultured cells of EAC still shed this virus.

Animals↗

Rearrangements of immunoglobulin genes during differentiation and evolution.

Immunoglobulin genes are shown to undergo dynamic rearrangements during differentiation as well as evolution. We have demonstrated that a complete immunoglobulin heavy chain gene is formed by at least two types of DNA rearrangement during B cell differentiation. The first type of rearrangement is V-D-J recombination to complete a variable region sequence and the second type is S-S recombination to switch a constant region sequence. Both types of recombination are accompanied by deletion of the intervening DNA segment. Structure and organization of CH genes are elucidated by molecular cloning and nucleotide sequence determination. Organization of H chain genes is summarized as VH-(unknown distance)-JH-(6.5 kb)-C mu-(4.5 kb)-C delta-(unknown distance)-C gamma 3-(34 kb)-C gamma 1-(21 kb)-C gamma 2b-(15 kb)-C gamma 2a-(14.5 kb)-C epsilon-(12.5 kb)-C alpha. The S-S recombination takes place at the S region which is located at the 5' side of each CH gene. Nucleotide sequence of the S region comprises tandem repetition of closely related sequences. The S-S recombination seems to be mediated by short common sequences shared among S regions. A sister chromatid exchange model was proposed as a mechanism for S-S recombination. Comparison of nucleotide sequences of CH genes indicates that immunoglobulin genes have scrambled by intervening sequence-mediated domain transfer during their evolution.

Animals↗

Reversed single-radial-immunodiffusion test: the method for the assay of the antibody to influenza A nucleoprotein.

The reversed single-radial-immunodiffusion (r-SRD) test using the avian-origin influenza A virus, A/chicken/Germany "N'/49 (Hav2Neql) disrupted with 1.0% sarkosyl, was established as the quantitative method for the assay of a type-specific antibody, particularly of an anti-nucleoprotein antibody, in human sera. Under the test conditions, human sera produced a definite opalescent zone around the well and the annulus area was found to have a high correlation to the antibody level of type A influenza nucleoprotein. The specificity of the opalescent zone produced in the test plate was confirmed with the specific antisera to each viral polypeptide and the adsorption procedures with the purified nucleoprotein. During an epidemic of H3N2 and H1N1 viruses, the r-SRD test was employed to estimate the infection ratio in junior high school students. The results demonstrated its convenience and high sensitivity in detecting the antibody rise to influenza A nucleoprotein. In addition, the age-distribution of the antibody level to influenza A nucleoprotein was examined and discussed. The results obtained strongly suggested that the r-SRD technique using the avian-origin influenza A virus provided a simple and reproducible method for the assay of the antibody level to influenza A nucleoprotein in a large scale seroepidemiology and in the serodiagnosis of influenza A virus infection.

Adolescent↗

Rotavirus infection in children with acute gastroenteritis in Ecuador.

Electron microscopic examination of stools of 702 infants and young children hospitalized in the Emergency Service of the Alejandro Mann Children's Hospital in Guayaquil, Ecuador, between August 1978 and October 1979 showed rotavirus to be present in 148 (21.1%). During the study period rotavirus was detected throughout the year, with no distinct seasonal variation. In addition to rotavirus, adenovirus was detected in stools of five (0.7%) of the patients and unidentified small round virus particles in seven (1.0%).

Acute Disease↗

Serological evidence of natural recombinant influenza virus (Hsw1N2) infection among pigs in Japan.

A new recombinant influenza A virus (Hsw1N2) infection among hogs in Miyagi prefecture, Japan, was confirmed by serological examinations. Nineteen out of twenty sera collected in one farm in January 1979 showed high haemagglutination inhibition antibody titres to Hsw1 antigen (A/New Jersey/8/76) and also significant neuraminidase inhibition antibody titres to N2 antigen of the Hong Kong 1973 variant (A/Port Chalmers/1/73) but not to N1 antigen. The results indicate the occurrence of genetic reassortment between Hsw1N1 and H3N2 viruses in Japanese pigs and spread of the recombinant in nature.

Animals↗

Isolation and characterization of an immunosuppressive acidic protein from ascitic fluids of cancer patients.

Analytical isoelectric focusing in polyacrylamide gel at pH 2.5 to pH 5 was used successfully to detect an acidic protein which can be found in large quantities in the sera of cancer patients but in only small amounts in the sera of healthy persons. The main peak of this acidic protein when obtained from cancer patients revealed a pI of 3.0, while the pI of that obtained from normal subjects was 3.1. The results obtained also demonstrated that qualitative and quantitative differences of such serum acidic proteins discriminate between sera of normal persons and cancer patients. Purification of this acidic protein (pI 3.0) was attempted with cancer ascitic fluids by successive ammonium sulfate precipitation, diethylaminoethyl cellulose column chromatography, Sephadex G-100 gel filtration, and preparative isoelectric focusing. When the purified acidic protein was characterized for physicochemical properties, it was found to have an isoelectric point of 3.0, to have a molecular weight of 50,000, and to contain 31.5% carbohydrate. Its behavior in immunodiffusion and immunoelectrophoresis was indistinguishable from that of normal human alpha 1-acid glycoprotein. However, in gel isoelectric focusing, in molecular weight, and also in carbohydrate content, the acidic protein isolated from cancer ascitic fluid differed from normal alpha 1-acid glycoprotein. Furthermore, this acidic protein was found to suppress both phytohemagglutinin-induced lymphocyte blast formation and mixed-lymphocytes reaction in vitro. The acidic protein, which we called "immunosuppressive acidic protein," and its biological activities were discussed regarding its possible role in the impairment of the immunological surveillance mechanism in the tumor-bearing host.

Ascitic Fluid↗

A non-histone chromatin protein that is a specific phosphate acceptor of nuclear cAMP-independent protein kinase from mouse spleen cells.

A non-histone chromatin protein (NHCP), which is specifically phosphorylated by a nuclear cAMP-independent protein kinase from mouse spleen cells in vitro, has been purified from calf thymus chromatin. SDS-polyacrylamide gel electrophoresis shows that the molecular weight of the purified NHCP (single peptide) is 13,000. This peptide consists of 14 amino acid residues and has high serine content (17.9%). However, no methionine, proline, or half-cysteine have been detected. The NHCP is a basic protein (isoelectric point, approximately 9.0), although it has high acidic amino acid content (26.2%). This protein serves as the most effective phosphate acceptor for the kinase in vitro when compared with other chromatin proteins such as histones; the Km value of the kinase for the NHCP is 3.65 x 10(-6) M, whereas that for histone H2a (Mr = 14,000) is 1.08 x 10(-5) M. The present finding that the NHCP phosphorylation by the kinase in vitro is remarkably stimulated by double-stranded DNA but inhibited by whole histone or histone H2a suggests that the phosphorylation may be controlled by both double-stranded DNA and histone H2a.

Amino Acids↗

The distribution of Gc subtypes among the mongoloid populations.

The polymorphism of Gc (group-specific components) has been investigated for a series of 3,160 individual samples from 11 Mongoloid populations in Asia and North and South America by isoelectric focusing on polyacrylamide gels. The samples fall into six Gc phenotypes which can be explained by the three common alleles, Gc1F, Gc1S, and Gc2, together with several variant phenotypes explained as the heterozygotes for the three common alleles. The distribution of Gc1F suballele appears to be considerably different from population to population among Mongoloids, ranging from 0.105 (Machiguenga Indians, Peru) to 0.609 (Kadazan, Borneo). A clear geographic cline from Southeast Asia into South America in Gc1F allele was observed in the populations. In general, Gc1F allele frequencies are lower in European populations and higher in African populations. The range of variability in the Gc1F values observed among the Asiatic populations is between the Africans and the Europeans.

Alleles↗

Prevalence of Williams e1 antigen in comparison with e2 antigen in hepatitis B antigen carriers and patients in hemodialysis unit.

The prevalence of both e1 and e2 antigens in 1,158 sera of asymptomatic HBsAg carriers, carriers in hemodialysis units, and HBsAg-negative blood donors was examined. The detection rate of e1 antigen was as high as 80% in asymptomatic carriers, 95% in hemodialysis patients, and even 13.1% in HBsAg-negative donors. All of the e1 antigen-positive specimens in such HBsAg-negative sera were found to have both or either anti-HBs and anti-HBc, suggesting the past history of Hepatitis B virus (HBV) infection of the donors. In the HBsAg-positive serum, the detection rate of e2 antigen (17%) was lower than that of e1 (80%), and all sera having e2 antigen were positive for e1 antigen. The titers of HBsAg, HBcAg, and anti-HBc in e2 antigen-positive sera were higher than that of sera detecting only e1 antigen. The appearance of e1 antigen and e2 antigen in the course of post-transfusion hepatitis B was studied with five cases. Retrospective study showed that three of them each received one unit of HBsAg-positive blood, and the other two received HBsAg-negative blood but with high-titered anti-HBc. In four cases out of five, in which e2 antigen was detected during the course of infection, the initial detection of e2 antigen occurred at or just before the elevation of liver enzyme levels. On the other hand, e1 antigen was detected relatively early after transfusion, and the time of onset. Moreover, the detection period of e1 antigen persisted longer, even after the disappearance of HBsAg antigenemia. These two separate studies suggest that not only e2 antigen but also e1 antigen are associated with the infection of HBV, but they are distinct from each other; the e2 antigen may have the properties of a signal of the viral activity in the patient as suggested by many others, but e1 antigen does not seem to bear such diagnostic values.

Adult↗