Biomedical subjects

Y Ohara

Publications and source records attributed to Y Ohara.

At least 109 records · Page 6Linked to original sources

PubMed1992

Infiltration of helper/inducer T lymphocytes heralds central nervous system damage in human T-cell leukemia virus infection.

Cellular infiltrates in new and old lesions in two cases of human T-cell leukemia virus associated myelopathy (HAM) were analyzed with anti-CD3 antibody and OPD4 antibody recognizing CD4 + CD45RO + T lymphocytes. A subset of CD4 lymphocytes with helper/inducer function and labeled with OPD4 constitutes up to 65% of CD3 cells in new lesions in the pons and the cervical cord. In contrast, nonhelper cells and macrophages were dominant in long-standing spinal cord lesions of these HAM cases and inflammatory lesions in two cases of Japanese encephalitis. Thus, unlike in viral infections, the central nervous system (CNS) tissue damage associated with human T-cell leukemia virus (HTLV-1) infection appeared to be heralded by the infiltration of helper/inducer T cells.

Antibodies, Monoclonal↗

PubMed1991

Effects of endothelin-1 on epicardial coronary tone, coronary blood flow, ECG-ST change and regional wall motion in anesthetized dogs.

The effects of intracoronary-administrated endothelin-1 on coronary hemodynamics and regional myocardial function were studied in anesthetized open-chest dogs. Epicardial coronary diameter (CoD) and coronary blood flow (CBF) were measured by a sonomicrometer of 10 MHz piezoelectric crystals and an electro-magnetic flow probe on the left circumflex coronary artery (LCX). Regional wall motion was sonomicrometrically measured at regions supplied by the LCX and left anterior descending artery (LAD) and electrocardiograms were recorded. Endothelin-1, administered as a bolus injections into the LCX via an intracoronary cannula, in a dose-dependent manner reduced COD and CBF. The extent of the reduction of COD and CBF at a dose-dependent manner reduced COD and CBF. The extent of the reduction of COD and CBF at a dose of 300 pmol was 12.3 +/- 1.5% (P less than 0.01) and 86 +/- 5% (P less than 0.01), respectively, of the control. The extent of CBF reduction and deterioration of systolic wall motion were linearly related with the dosage of endothelin-1. ST-elevation (lead II) and fatal ECG abnormalities, including complete atrioventricular block or ventricular fibrillation, were observed with doses above 60 and 100 pmol, respectively. Coronary angiography revealed that filling defects of dye were propagated from the third or distal branches to those of more proximal arteries when the doses of endothelin-1 were cumulatively infused into the LCX. Accordingly, lethal myocardial ischemia induced by endothelin-1 is produced by critical obstruction of rather small coronary vessels.

Animals↗

PubMed1991

Mutagenicity of (p-nitrophenyl)adenines in Salmonella typhimurium.

Adenine derivatives having a p-nitrophenyl group at position 2, 8, or 9 were directly mutagenic towards Salmonella typhimurium strains TA98 and TA100, whereas N6-(p-nitrophenyl)adenine was not mutagenic. 2,9- And 8,9-bis-(p-nitrophenyl)adenines were also mutagenic, but N6,9-bis-(p-nitrophenyl)adenine was not. The study on 13 (p-nitrophenyl)adenine derivatives for their Salmonella mutagenicity indicates that only those having a p-nitrophenyl ring directly linked to the purine ring are mutagenic, implying the importance of the coplanar character of the nitrophenyl and the purine rings. The nitro group seems essential for the mutagenicity, as shown from the results of assays using nitroarene-sensitive and -insensitive Salmonella strains. The mutagenic potency of this class of compounds is high, comparable to that of 2-nitrofluorene.

Adenine↗

PubMed1991

An indirect microhemagglutination test for Lyme disease.

We have developed an indirect microhemagglutination test (IMHA) for detecting antibodies to Borrelia burgdorferi using formalin-fixed chicken erythrocytes sensitized with a sonicated extract of the bacteria. The specificity of IMHA for Lyme disease was compared with that of a conventional indirect immunoperoxidase technique (IP) using sera from the patients with syphilis, randomly-chosen outpatients unrelated to Lyme disease, and from normal individuals. The IMHA was more specific than IP, giving little cross-reaction with syphilis. The IMHA also gave little background reactions with the sera of individuals unrelated to Lyme disease or syphilis. Therefore, the IMHA could be a useful test for the serodiagnosis of Lyme disease.

Antibodies, Bacterial↗

PubMed1990

Intraneuronal laminin-like immunoreactivity in the human central nervous system.

Because laminin possesses potent neurotrophic activity, laminin-like immunoreactivity was investigated in formalin-fixed human brains, using affinity-purified anti-human placental laminin rabbit serum. Distinct laminin-like immunoreactivity was observed in neuronal soma of certain nuclear groups, and a 180-kDa band was noted in an immunoblot study of the supernatant of brain homogenate. These observations imply that many but not all central neurons have laminin-like immunoreactive molecules. Their functional role, however, remains to be clarified.

Autopsy↗

PubMed1990

2-(p-Nitrophenyl)-2'-deoxyadenosine, a new type of mutagenic nucleoside.

A crude preparation of 2-phenyladenosine was found to be mutagenic in the Ames Salmonella assay. In the purification of this preparation, it was revealed that 2-phenyladenosine itself was nonmutagenic but that 2-(m- and p-nitrophenyl)-adenosines (5m,p) contaminating the sample were the mutagenic principles. A structure-activity relationship study was carried out, and it was found that 5p, 2-(p-nitrophenyl)-adenine (7p), and 2-(p-nitrophenyl)-2'-deoxyadenosine (15p) were strongly mutagenic toward S. typhimurium TA98 and TA100 without metabolic activation, the potency being in the order 15p greater than 7p greater than 5p. The potency of 15p in TA98 was one order of magnitude greater than that of 4-nitroquinoline N-oxide. 15p also showed mutagenicity in the mouse cell line FM3A in culture.

Adenosine↗

PubMed1990

Targeting of adoptively transferred experimental allergic encephalitis lesion at the sites of wallerian degeneration.

To clarify the implication of the major histocompatibility complex class II (Ia) antigen induction in microglia following Wallerian degeneration in the central nervous system (CNS), experimental allergic encephalitis (EAE) was adoptively transferred to Lewis rats in which Ia antigens had been induced in microglia at the sites of Wallerian degeneration. In addition to randomly distributed typical EAE lesions, the recipient rats developed distinct inflammatory lesions in accord with the distribution of Ia-positive microglia; i.e., in the ipsilateral thalamus after cortical cryoinjury, and in the ipsilateral optic nerve, the contralateral optic tract and superior colliculus after unilateral eye ball enucleation. Thus, the EAE locus may be targeted by this approach. The inflammatory response was inducible by transfer of myelin basic protein-stimulated lymphocytes but not by transfer of phytohemagglutinin-stimulated or non-stimulated lymphocytes. When examined using monoclonal antibody surface markers; OX-6 for Ia antigen, W3/13 for pan T lymphocyte and OX-8 for cytotoxic/suppresser T lymphocyte, the types of lymphocytes in these lesions did not differ from those in ordinary EAE lesions in the spinal cord. The potential role of non-immunologically induced Ia-positive cell clusters that serve as a target for autoimmune CNS diseases was discussed.

Animals↗

PubMed1990

Cytotropism of Theiler's murine encephalomyelitis viruses in oligodendrocyte-enriched cultures.

The cytotropism of two strains, GDVII and DA, of Theiler's murine encephalomyelitis viruses (TMEV) was studied in the oligodendrocyte-enriched murine neural cell cultures. Both GDVII and DA caused cytopathic effects in the neural cell cultures, and double immunostaining for galactocerebroside (Gal-Cer), a marker molecule for oligodendrocyte, and viral antigens disclosed a dual expression of Gal-Cer and viral antigens in over 80% of cells in both cultures 24 h after infection with either GDVII or DA. The kinetics of cell-free and cell-associated infectivity were not significantly different between two cultures. These in vitro observations suggest that neither replication in oligodendrocyte nor cell-associated infectivity is a sole factor in discriminating those two subgroups of TMEV with regard to the demyelinating activity, and that virus cell binding may play an important role in virus persistence and TMEV-induced demyelination.

Animals↗

PubMed1990

Microagglutination test for early and specific serodiagnosis of tularemia.

A microagglutination test with safranin-stained Francisella tularensis antigen was compared with a conventional tube agglutination test for the serodiagnosis of tularemia. The microagglutination test was performed in round-bottom microtiter plates by using 0.025 ml of the antisera and of the antigen. The antibody titers obtained by using the microagglutination test were 8 to 64 times higher than those seen with the tube agglutination. By the microagglutination test, the serum agglutinins were detected 3 days earlier in rabbits and 9 days earlier in humans than by the tube agglutination test. The microagglutination test also detected residual circulating antibodies in humans more than 20 years after recovery from infection. These early agglutinins were shown to be in the immunoglobulin M class because of their sensitivities to 2-mercaptoethanol. No significant group agglutination reaction with Brucella abortus was observed. These observations indicate that the microagglutination test is a useful tool for the early and specific serodiagnosis of tularemia.

Agglutination Tests↗

PubMed1989

Viral infectious complementary-DNA studies may identify nonviral genes critical to central nervous system disease.

A major interest of modern science and medicine is the delineation of genes that cause disease. In the case of cancer, the study of viral oncogenic genes led to the recognition of similar human genes that play an important role in this disease. In an analogous fashion, the identification of viral genes important in central nervous system disease may lead to the recognition of related cellular genes that are important in nonviral central nervous system disease. New molecular techniques now provide tools for identification of pathogenic viral genes and elucidation of mechanisms of disease production. Positive-strand RNA viruses such as picornaviruses provide an especially attractive model system for studies of central nervous system disease-producing genes. A limitation in molecular studies of these viruses has resulted from an inability to use restriction enzymes, since these enzymes are active against DNA and not RNA. This limitation has recently been overcome with the preparation of infectious picornavirus complementary-DNA. This review highlights the importance of infectious complementary-DNA in pathogenesis studies and provides a glimpse of the impact of such studies on neurology.

DNA↗

PubMed1989

Mongolian spots associated with cleft lip.

Of the present series comprising 66 newborns with cleft lip, 13 (20%) had pigmented macules in the labial skin on the lateral side of the cleft. Histological examination using serial sections were performed on 47 cases and showed evidence of dermal melanocytosis in 40 cases (85%) consisting of 33 (70%) without clinically detectable macules and 7 (15%) with obvious pigmented macules. The fusiform cells in the dermis were positive for dopa reaction and anti-melanocyte antibody. The high incidence of dermal melanocytosis is comparable to that of common Mongolian spots in Asian babies.

Cleft Lip↗

PubMed1989

Neurotoxic activity in HTLV-I carrier lymphocyte culture.

A close association between human T-lymphotropic virus type I (HTLV-I) infection and a group of chronic myelopathies of unknown etiology has recently been established and the name "HTLV-I associated myelopathy" (HAM) has been coined. Although the mechanism of neural tissue damage in HAM remains virtually unknown, several lines of evidence suggest the involvement of a soluble factor(s) including cytokines and viral proteins in the disease process. In this study, we examined cytopathic effects of the supernatants from 6 HTLV-I carrier human T lymphocyte cell lines on 4 human and one murine neuroblastoma cell lines, and 2 human glioma cell lines. Among 6 lymphocyte cell culture supernatants, only 1 from MT-2 cell culture repeatedly exerted cytopathic effects on human neuroblastoma cells, particularly on IMR-32 cells: marked retraction of neurites leading to cellular clumping. This activity was neither abolished by treatment of the medium at 80 degrees C for 30 min or by UV-irradiation, nor was it neutralized by anti-HTLV-I antibodies. The MT-2 supernatant also induced mild cytopathic changes in 2 other human neuroblastoma cell lines and 2 human glioma cell lines. This activity was abolished by treatment of the medium at 80 degrees C for 30 min but not at 56 degrees C for 30 min. Myelinated murine cerebellum explants and other cell lines showed no morphological changes when incubated with the MT-2 supernatant. In addition, the growth of THP-1 cells, a monocyte/macrophage lineage cell line, was remarkably suppressed when maintained in the MT-2 conditioned medium, accompanied by enhancement of phagocytic activity. The THP-1 conditioned medium, on the other hand, suppressed tumor necrosis factor (TNF) activity detected in the MT-2 culture. These observations suggest that HTLV-I induced cytokines may directly act on neural cells, but their action appears to be regulated by the intricate interactions of lymphocytic and monocytic cells.

Animals↗

PubMed1989

Defective immune response to Epstein-Barr virus in patients with acute lymphocytic leukemia.

Thirteen children with acute lymphocytic leukemia (ALL) receiving maintenance chemotherapy were tested for anti-Epstein-Barr virus (EBV) antibodies, EBV specific cytotoxic T lymphocyte (EBV-CTL) activity and spontaneous cytotoxicity against Raji cells in order to define the defective cellular immunity in ALL children during complete remission. Among 10 seropositive patients, anti-virus capsid antigen (VCA) antibody titer varied from 1:20 to 1:320 and anti-EBV nuclear antigen (EBNA) antibody was not detectable in four. No patients were positive for anti-early antigen (EA) antibody. EBV-CTL activity and interleukin 2 (IL-2) or interferon alpha (IFN-alpha) augmented EBV-CTL activity in eight seropositive patients was significantly lower than that in the seropositive age matched control group. IFN-alpha, OK-432 or IL-2 augmented spontaneous cytotoxicity were also significantly lower in the patients compared to those in the control group. These defective killer cell activities may allow EBV-infections to enter a severe, fulminant or persistently active state in the patients with ALL receiving aggressive maintenance chemotherapy.

Antibodies, Viral↗

PubMed1989

Infectious cDNA clones of the DA strain of Theiler's murine encephalomyelitis virus.

The DA strain and other members of the TO subgroup of Theiler's murine encephalomyelitis viruses cause a persistent demyelinating infection, whereas the GDVII strain and other GDVII subgroup strains cause an acute lethal polioencephalomyelitis. We generated an infectious DA cDNA clone inserted into a transcription vector. Virus derived from transfection of transcripts produced a demyelinating disease indistinguishable from that of wild-type virus. The infectious clone provides a critical reagent for the production of interstrain recombinant viruses to help identify genetic loci responsible for the biological activities of the strains.

Animals↗

PubMed1989

Serial assessment of myocardial infarction by using gated MR imaging and Gd-DTPA.

In order to assess the usefulness of Gd-DTPA in the evaluation of myocardial infarction, 17 patients were examined with gated MR imaging. Scans were made by using a spin-echo pulse sequence before and after IV administration of 0.15 mmol/kg of Gd-DTPA. The images were made at four intervals (average of 5, 12, 30, and 90 days) after the onset of the infarction. Gd-DTPA uptake at the infarcted area was graded as marked, moderate, or no increase in signal intensity by visual inspection. At these four time intervals, an area of increased signal intensity in the infarcted myocardium was detected on T1-weighted images after administration of Gd-DTPA in 14 (82%) of 17 cases, 16 (94%) of 17 cases, six (38%) of 16 cases, and three (21%) of 14 cases, respectively. Markedly increased signal intensity in infarcted areas was shown on T1-weighted images with Gd-DTPA at 5 and 12 days. The ratio of gadolinium uptake in the infarcted area to that in normal myocardium also was evaluated. At 5 and 12 days, the mean increase in signal intensity in the infarcted area was significantly higher than that in a normal area, but not at 30 and 90 days. Increased signal intensity also was apparent on T2-weighted images without Gd-DTPA at 5 and 12 days; however, the use of late echo reduced the signal-to-noise ratio, leading to image degradation. Uptake of Gd-DTPA was a positive marker in acute myocardial infarction, but no significant uptake of Gd-DTPA occurred in chronic myocardial infarction.

Contrast Media↗

PubMed1988

Molecular cloning and sequence determination of DA strain of Theiler's murine encephalomyelitis viruses.

Theiler's murine encephalomyelitis viruses (TMEV) belong to the Picornaviridae, and are divided into two subgroups. TO subgroup strains produce a persistent demyelinating central nervous system infection in mice, while GDVII subgroup strains cause acute polioencephalomyelitis. We generated three overlapping clones of the genome of DA strain, a member of TO subgroup. Sequence analysis revealed that the genome is 8093 nucleotides long with a poly(A) tail. The 5' noncoding region stretches from nucleotides 1 to 1065 and lacks a poly(C) tract. The open reading frame stretches from 1066 to 7968 and encodes 2301 amino acids. DA strain sequence is more closely related to members of the Cardiovirus genus than to members of other Picornavirus genera. Comparison with sequence of BeAn strain, another TO subgroup strain, showed that the P1 area has the greatest number of differences, while the noncoding regions are more well-conserved. The three overlapping clones will be important in recombinant infectious cDNA studies between strains of both subgroups.

Amino Acid Sequence↗

PubMed1988

Trypsin-sensitive neutralization site on VP1 of Theiler's murine encephalomyelitis viruses.

We generated Theiler's murine encephalomyelitis virus mutants resistant to several neutralizing monoclonal antibodies (MAbs) having their epitopes near a trypsin cleavage site of VP1. Neutralization and Western blot (immunoblot) studies suggest that two of the MAbs have identical epitopes that partly overlap the epitope of a third MAb. Sequencing of RNA of the mutants localized the epitopes to a site near the carboxyl end of VP1. The limited diversity of nucleotide changes seen in the mutants and the immunodominance of the site suggest that the carboxyl end of VP1 may have an important function.

Animals↗

PubMed1988

Defective killer cell activity in patients with chronic active Epstein-Barr virus infection.

Natural killer (NK) cell activity, lymphokine activated killer (LAK) activity and Epstein-Barr virus specific cytotoxic T lymphocyte (EBV-CTL) activity were examined in 10 children with chronic active EB-virus infection and an adult with persistently positive early antigen-antibody to EB-virus. NK cell activity against erythroleukemia cell line K-562 was significantly (p less than 0.005) lower in the patients (22.3 +/- 8.5%, mean +/- SD) than in normal controls (40.4 +/- 15.9%). Spontaneous cytotoxicity against an EB-virus transformed autologous lymphoblastoid cell line was 15.0 +/- 7.6% in the patients, and was comparable to spontaneous cytotoxicity activity in normal controls (11.7 +/- 4.3%). LAK activity against Raji cells was significantly (p less than 0.02) lower in the patients (14.6 +/- 11.4%) than in normal controls (29.2 +/- 15.9%). EBV-CTL activity against an EB-virus transformed autologous lymphoblastoid cell line was significantly (p less than 0.005) lower in the patients (11.8 +/- 5.5%) than in seropositive normal controls (33.7 +/- 14.7%). No regression of the lymphoblastoid cell line was observed when EBV-CTL activity of the patients was tested by regression assay. It is conceivable that defects in both EB-virus specific and nonspecific killer cell activities play important roles in the pathogenetic abnormalities which allow EB-virus infection to progress to a chronic active state.

Cell Line, Transformed↗