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Biomedical subjects

N Inoue

Publications and source records attributed to N Inoue.

At least 433 records · Page 24Linked to original sources
PubMed1991

The domain of Epstein-Barr virus nuclear antigen 1 essential for binding to oriP region has a sequence fitted for the hypothetical basic-helix-loop-helix structure.

The domain of Epstein-Barr virus nuclear antigen 1 (EBNA-1) which is essential for binding to a region containing oriP, an episomal replication origin of EBV DNA, was analyzed by DNA binding assay with beta-galactosidase-EBNA-1 fusion proteins. It was revealed that a 159-amino acid (aa) domain, 460-618 aa, of EBNA-1 retained the oriP-binding activity and the domain's activity was abolished by a deletion of 29 aa from its amino-terminal end and by a 38 aa deletion from its carboxyl-end as well. One of five monoclonal antibodies against EBNA-1 specifically inhibited the binding of the beta-galactosidase-EBNA-1 fusion protein to the oriP region. The epitope recognized by the monoclonal antibody was mapped in the crucial 29 aa region. An analysis of the domain's putative secondary structure and a computer search of amino acid sequence homology indicated that the 159-aa domain contains the hypothetical basic-helix-loop-helix structure which is considered to be a common characteristic structure of a family of DNA binding proteins. Examinations of DNA binding activity of the other EBNA polypeptides with a series of fusion proteins and similar structural analyses of their amino acid sequences were also performed. This study suggests that EBNA-1 is a constituent of the family of DNA binding proteins which are involved in transcriptional regulation critical for cell differentiation or cell-type determination.

Amino Acid Sequence↗
PubMed1991

Analysis of antibody titers to Epstein-Barr virus nuclear antigens in sera of patients with Sjögren's syndrome and with rheumatoid arthritis.

To examine if Epstein-Barr virus (EBV) infection is associated with the two autoimmune diseases, Sjögren's syndrome and rheumatoid arthritis, IgG antibody titers of sera from patients with the disorders were evaluated for five constituents of EBV nuclear antigens (EBNA-1, -2, -3, -4, and -6). To circumvent interference by autoantibodies in the sera, fusion proteins synthesized in Escherichia coli were used as specific antigens. By ELISA the average IgG antibody titers to domains of the five EBNAs, especially the amino-terminal domain of EBNA-2, in sera of patients with Sjögren's syndrome were slightly higher than those in normal sera. The tendency of sera from Sjögren's syndrome patients to have higher reactivities to the EBNA domains was also observed by immunoblotting. By comparison, few heightened serologic responses to EBNAs were observed in sera from patients with rheumatoid arthritis. Further analyses are required to determine if EBV is associated with Sjögren's syndrome in any way.

Antibodies, Viral↗
PubMed1991

Lysis of fresh human tumor cells by autologous peripheral blood lymphocytes and tumor-infiltrating lymphocytes activated by PSK.

The protein-bound polysaccharide PSK was tested for the ability to induce in vitro autologous tumor killing (ATK) activity in human cancer patients. Peripheral blood lymphocytes (PBL) and tumor-infiltrating lymphocytes (TIL) demonstrated various levels of cytotoxicity against autologous, freshly isolated tumor cells. When PBL and TIL were cultured overnight with PSK, ATK activity was induced in previously non-reactive cases and augmented in previously reactive samples. The PSK effect was observed with PSK concentrations of 10-100 micrograms/ml that could be obtained in the blood of cancer patients who received standard oral administration of PSK. The manifestation of PSK-induced ATK required active cell metabolism and RNA and protein syntheses, but not DNA synthesis of lymphocytes. PSK-induced enhancement of ATK was not abrogated by monoclonal antibodies (mAb) directed against interferon (IFN) alpha or IFN gamma. In addition, mAb that neutralized interleukin-2 (IL-2) or mAb reactive with alpha-chain or beta-chain of IL-2 receptors (IL-2R) had no effect on PSK-induced ATK activity. Supernatants from PSK-stimulated lymphocyte cultures did not induce ATK. Cell fractionation experiments revealed that CD3-CD16+ large granular lymphocytes (LGL) and/or CD3+CD16- T lymphocytes were responsible for both spontaneous and PSK-induced ATK. PSK-activated LGL, but not T lymphocytes expressed lysis of fresh allogeneic tumor cells. These results indicate that PSK activates PBL and TIL to exhibit ATK independently of IL-2/IL-2R systems.

Adult↗
PubMed1991

Cytomegalovirus vasculitis accompanied by an exuberant fibroblastic reaction in the intestine of an AIDS patient.

A case of cytomegalovirus (CMV) vasculitis in the intestine of a patient with acquired immune deficiency syndrome (AIDS) is reported. The distal jejunum and ileum had multiple well-demarcated mucosal ulcers and microscopic examination revealed an unusual, exuberant fibroblastic proliferation in the ulcer base. Amidst these fibroblasts, there were several small blood vessels of which the endothelial cells contained cytomegalic inclusion bodies. The lesion showed a Kaposi's sarcoma-like appearance, but spindle cells were negative in immunostaining for factor VIII-related antigen or Ulex europaeus agglutinin-1. Although the CMV infection was observed in almost all organs, the exuberant fibroblastic proliferation seen in the intestine was not found in other organs. This lesion might represent a peculiar reaction of the immunologically compromised host to the CMV in the intestinal blood vessels.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Evaluation of a filtration lymphocytapheresis (LCP) device for use in the treatment of patients with rheumatoid arthritis.

A practical on-line lymphocytapheresis (LCP) system using a leukapheresis filter (Cellsorba, Asahi Medical Co.) was evaluated in six patients with refractory rheumatoid arthritis. This filter consists of nonwoven fine polyester fiber wound around a porous cylinder. The blood was passed through the polyester fiber at a flow rate of 50 ml/min for 60 min. LCP was carried out once a week in the first month and biweekly in the next 2 months. An average of 98% of the leukocytes that entered the filter (1.27 x 10(10) cells) and 100% of the lymphocytes that entered the filter (3.66 x 10(9) cells) were removed in the first LCP. A total of 96.6% of the platelets and 2.7% of the erythrocytes that entered the filter were also removed. All of the patients showed clinical improvement in morning stiffness, Lansbury articular index, and functional capacity, with no adverse reaction. The number of circulating erythrocytes and platelets and the concentration of various serum components showed no significant change during the treatments. This LCP system required no fresh frozen plasma, albumin, or other blood transfusion. The number of circulating lymphocytes decreased to 65-70% of the pretreatment circulating lymphocyte count at the last procedure, with a decrease in the ratio of Leu3a positive cells to Leu2a positive cells. The proliferative response to phytohemagglutinin and concanavalin A was improved. These data suggest that LCP to remove approximately 3 x 10(9) lymphocytes once a week or biweekly has an immunomodulatory effect.

Arthritis, Rheumatoid↗
PubMed1991

Transcription and initiation of ColE1 DNA replication in Escherichia coli K-12.

By S1 nuclease protection mapping, we characterized RNA transcripts and nascent ColE1 DNA synthesized in wild-type Escherichia coli cells after infection with lambda-mini-ColE1 hybrid bacteriophages. Transcription of the RNA II region of ColE1 DNA in vivo starts mostly from the RNA II promoter, which was identified by in vitro experiments, and ends at or near the ori site. Synthesis of the leading strand of ColE1 DNA was found to start at the ori site. Nevertheless, the molar ratio of the nascent DNA to the synthesized transcripts ending at the ori site was less than 0.05. In bacterial rnh mutants whose RNase H activities were less than 0.06% of that of the wild type, transcription patterns, as well as nascent DNA synthesis, were still similar to those in rnh+ cells. However, in bacteria whose rnh gene was interrupted by insertion of a drug resistance gene, the number of transcripts ending at the ori site was much reduced and that of transcripts reading through the ori site was definitely increased relative to that observed in wild-type bacteria. These results suggested that cleavage of the RNA transcript at the ori site in vivo is dependent on RNase H activity, as demonstrated in the in vitro system, but most of the cleaved RNA is unable to prime initiation of ColE1 DNA synthesis efficiently.

Bacteriocin Plasmids↗
PubMed1991

Dose dependent effects of inhaled ethylene oxide on spermatogenesis in rats.

Male Wistar rats were exposed to ethylene oxide (EO) at concentrations of 50, 100, or 250 ppm for six hours a day, on five days a week for 13 weeks. Dose effect relations of inhaled EO on spermatogenesis were evaluated from testicular and epididymal weights, histopathological changes and lactate dehydrogenase X (LDH X) activity in the testis, and sperm counts and sperm head abnormalities in the epididymis. At 250 ppm, a decrease in epididymal weights, slight degenerations in the seminiferous tubules, decreased sperm counts, and increased numbers of abnormal sperm heads in the tail of the epididymis were found; these were not seen at lower doses. When the abnormal sperm heads were classified into immature types and teratic types, the number of immature heads increased only at 250 ppm. On the other hand, the teratic type had increased at doses of 50 and 100 ppm EO when compared with the control group. Hence, subchronic inhalation of EO at low concentrations affects spermatogenesis in rats.

Alkylating Agents↗
PubMed1991

[Effect of protoporphyrin IX on the induction of respiratory impairment of hepatic mitochondria by carbon tetrachloride in rats].

The effect of pretreatment with protoporphyrin IX (PP) on the impairment of hepatic mitochondrial respiration induced by carbon tetrachloride (CCl4) was studied in rats. Treatment of animals intraperitoneally with CCl4 resulted in marked impairment of states 4 and 3 respirations, respiratory control and oxidative phosphorylation of mitochondria in the presence of succinate, beta-hydroxybutyrate or glutamate as substrates. The PP, given intravenously, caused no alterations in those mitochondrial functions. The treatment with PP prior to the administration of CCl4 inhibited the induction of mitochondrial respiratory impairment by CCl4. CCl4 increased markedly the contents of lipid peroxide in the liver but not those in the mitochondria. The increase of hepatic lipid peroxides by CCl4 was markedly reduced by the pretreatment with PP. These results indicate that PP effectively protects the mitochondria from the functional disorder caused by CCl4.

Animals↗
PubMed1991

[Reoperation of primary tissue failure of bioprosthesis in the mitral position].

The surgical results of 38 patients who underwent reoperation for primary tissue failure of bioprosthesis in the mitral position between May 1982 and June 1990 were analyzed to determine the risk factors affecting the hospital mortality. The type of bioprostheses requiring reoperation were Hancock valve in 21 patients, Liotta valve in 15 patients and Mitroflow valve in 2 patients. Twenty-five preoperative and perioperative variables were collected and analyzed by univariate statistics using chi 2 test or Student's test. Four of thirty eight patients died postoperatively in the hospital, yielding an overall mortality of 10.5%. The causes of hospital mortality were low output syndrome in 2 patients and multiple organ failure in 2 patients. By univariate analysis, male, NYHA IV class, prosthetic stenosis, hepatic failure, renal failure, and pulmonary failure were risk factors predictive of high hospital mortality. In spite of recent improvement of surgical technique and myocardial protection, the hospital mortality of patients with NYHA IV class and advanced organ failure still remains unacceptable. Therefore, it is essential to perform reoperation for primary tissue failure of bioprosthesis before severe myocardial decompensation occurs. To accomplish this goal, patients with bioprosthesis who survived beyond the certain time should be followed periodically using echocardiogram.

Adult↗
PubMed1991

[Surgical repair of descending aortic aneurysms--experience in 100 patients under partial cardiopulmonary bypass].

Between 1975 and 1986, 100 consecutive patients with aneurysms of the descending thoracic (84 cases) or the thoracoabdominal aorta (16 cases) underwent surgical repair. Intraluminal graft inclusion procedure was employed in principle under routine circulatory support with partial cardiopulmonary bypass. In this study, overall surgical results were reviewed, and multiple factors discriminately contributing to early results were assessed using multivariate analysis (quantification theory type II) to determine if this therapeutic modality is pertinent. Fifty-five patients had non-dissecting, 42 had dissecting aneurysms and 3 had pseudoaneurysms. Seventeen patients were treated in the emergency setting. Perioperative or early deaths occurred in 14 patients. Mortality increased with advanced age (greater than 70 years) and with atherosclerotic aneurysms, especially when they involved the entire thoracic or thoracoabdominal aorta. Operative mortality during the last 5 years of the study was 9.3%: significantly lower than the figure in the first 5 years of 28% (p = 0.0198). The incidence of renal dysfunction (7.4%) or paraplegia (2.1%) was not related to aortic cross-clamp time, and both were markedly decreased to 3.8% and 0.0%, respectively, when the cases of thoracoabdominal aneurysms were excluded. There were 8 cases of exploration for postoperative hemorrhage and 6 cases of pulmonary insufficiency requiring more than 3 days of mechanical ventilation. Prolonged bypass time was a discriminative risk factor for these two complications. Cerebral vascular accidents developed in 5 patients, three of them terminated in death. In spite of partial bypass, the factors of advanced age, atherosclerosis, and cross-clamp on the aortic arch were defined responsible for brain stroke.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

[Collins blood diluting reperfusion--an effective measure of controlled reperfusion for the heart hypothermically preserved for 24 hours in modified Collins solution].

Controlled reperfusion is assumed to provide an appropriate environment surrounding the ischemic cardiac tissue at the initial reperfusion phase. Hence, this procedure might play a key role in resuscitating the long term preserved hearts. This study was designed to assess the efficacy of the newly devised reperfusion method; namely Collins Blood Diluting Reperfusion (CBDR), for those hearts subjected to 24-hours cold (4 degrees C) storage in modified Collins (MC) solution. Coronary reperfusion is commenced with the MC solution, and the oxygenated blood is successively added to dilute this perfusate with gradual rewarming under controlled perfusion pressure. Initial reperfusate, therefore, is supposed to be a blood cardioplegia with low Ca2+ and high Mg2+ content. During this procedure, any difference in the ionic composition between the storage solution and the reperfusate is completely abolished and myocardium is free from hastiness of temperature elevation. Using an isolated isovolum contracting heart prepared with an ex vivo apparatus incorporating a support dog, each heart was reperfused by unmodified blood (Group I: n = 7) or CBDR method (Group II: n = 10) under equally controlled low perfusion pressure. There was no difference in the myocardial creatine phosphate level between the 2 groups. However, the adenosine triphosphate content, which had been depleted to 30% of the preischemic level during the 24-hour preservation period, was restored to 52.0% after CBDR procedure (p less than 0.01) and consequently to 57.9% of the control at 60 minutes after reperfusion. Group I showed a significantly lower repletion effect at this phase (41.2% control; p less than 0.05 versus group II).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1991

[Multiple discriminant analysis for prognosis of refractory anemia].

Forty-eight patients with refractory anemia (RA) were retrospectively analyzed for their prognosis and subclassified into three groups: 12 patients with hematological improvement (A), 23 patients with no changes (B), and 13 patients with progression to RAEB or acute leukemia (C). For all patients, the median survival were 49.2 months, and the rate of leukemic transformation was 16%. The median survivals were 60.6, 32.1, and 17.9 months, respectively, for groups A, B and C. The factors indicating poor prognosis were low reticulocyte counts, low neutrophil alkaline phosphatase activity, low% red cell utilization, high M/E ratio, high blast percentage in the bone marrow and cytological abnormalities in the granulocyte and megakaryocyte series. By using multiple discriminant analysis, we obtained a formula for the prognostic estimation with a discrimination probability of 62.5%. This formula could predict either the patients with good (Y greater than 0.85) or poor (Y less than 0.59) prognosis, and might be useful to select the treatment for this intractable anemia at the time of diagnosis.

Adolescent↗
PubMed1991

[Coombs negative autoimmune hemolytic anemia in a patient with myelodysplastic syndrome].

A 29 year-old-man who had been diagnosed as having myelodysplastic syndrome (MDS) in August 1985 was re-admitted to our hospital because of fever and palpitation. His peripheral blood showed severe pancytopenia and bone marrow findings remained to be compatible with MDS (refractory anemia), but karyotype of bone marrow cells revealed 7 monosomy in 17 of 20 metaphases examined. Other laboratory findings revealed decreased serum haptoglobin, positive urine hemosiderin and the normal resistance of red cell membrane. In addition, both Ham test and sugar water test were negative. The titer of cold agglutinin was low, Donath-Landsteiner antibody was not detected. These findings suggested the association of autoimmune hemolytic anemia (AIHA), although both direct and indirect Coombs' test were negative. After administration of 50mg of prednisolone daily, the frequency of red cell transfusion was markedly decreased and transfused red cell life span was prolonged from 10.4 days to 27 days. Afterward, his hematological status rapidly transformed into that of acute nonlymphocytic leukemia about 13 months after admission and he died of gastrointestinal bleeding and cerebral bleeding. Cases of MDS with immunological disorder have been reported. This is, however, the first case of MDS associated with Coombs negative AIHA.

Adult↗
PubMed1991

[L-asparaginase-induced hyperlipidemia in a case of acute lymphoblastic leukemia].

A 15-y-o girl who had relapsed acute lymphoblastic leukemia, followed by the two-years complete remission, was treated with a reinduction chemotherapy including methotrexate, vincristine, L-asparaginase and dexamethasone (MOAD). During the chemotherapy, a remarkable hyperlipidemia has developed. The plasma levels of triglyceride and total cholesterol reached 14,450 mg/dl and 1,750 mg/dl, respectively. The laboratory data strongly suggest that L-asparaginase could induce this hyperlipidemia of Friedrickson type V. We could successfully reduce the levels of triglyceride and total cholesterol to the normal range by LDL-apheresis, and treat the patient with the chemotherapy excluding L-asparaginase to attain the second CR.

Adolescent↗
PubMed1990

[Effects of ethylene glycol on hepatic microsomal cytochrome P-450].

The effect of ethylene glycol on rat hepatic microsomal cytochrome P-450 was studied in vitro and in vivo. The destruction of cytochrome P-450 was not seen in vitro. The addition of 1 mM NADPH also did not change. When ethylene glycol was added to drinking water at a concentration of 1.0% for 7 days, there was no change in the contents of microsomal protein, cytochrome P-450, b5 and heme. While NADPH-cytochrome C reductase activity of the exposed group did not change, NADH-ferricyanide reductase activity increased significantly.

Animals↗