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Biomedical subjects

I Kinoshita

Publications and source records attributed to I Kinoshita.

At least 55 records · Page 3Linked to original sources
PubMed1995

Human papillomavirus type 18 DNA and E6-E7 mRNA are detected in squamous cell carcinoma and adenocarcinoma of the lung.

To provide an accurate evaluation of the association of human papillomavirus (HPV) with lung cancer, 36 cases of lung cancer were analysed for HPV DNAs by polymerase chain reaction (PCR) with dot-blot and Southern blot analyses, and for the transcripts from the E6-E7 transforming region by in situ hybridisation (ISH). HPV-18 DNA was detected in three (8%) of 36 specimens; histologically, in one (10%) of 10 squamous cell carcinomas and two (9%) of 22 adenocarcinomas. Neither HPV-16 nor -33 DNA was detected in any cases examined. Expression of E6-E7 mRNA was confirmed in the cases which contained, HPV-18 DNA. HPV-18 may play an important role in the development and progression of cancer in some cases of both squamous cell carcinoma and adenocarcinoma of the lung.

Adenocarcinoma↗
PubMed1995

Successful histocompatible myoblast transplantation in dystrophin-deficient mdx mouse despite the production of antibodies against dystrophin.

Myoblast transplantation has been considered a potential treatment for some muscular disorders. It has proven very successful, however, only in immunodeficient or immunosuppressed mice. In this study, myoblasts from C57BL10J +/+ mice were transplanted, with no immunosuppressive treatment, in the tibialis anterior of fully histocompatible but dystrophin-deficient C57BL10J mdx/mdx mice. One to 9 months after transplantation, the success of the graft was evaluated by immunohistochemistry. All the transplanted mice (n = 24) developed dystrophin-positive fibers following transplantation. Depending on myoblast cultures, transplantations, and time of analysis, the mice presented 15 to 80% of dystrophin-positive fibers in transplanted muscles. These fibers were correctly oriented and they were either from donor or hybrid origin. The dystrophin-positive fibers remained stable up to 9 months. Possible humoral and cellular immune responses were investigated after grafting. Antibodies directed against dystrophin and/or muscle membrane were developed by 58% of the mice as demonstrated by immunohistochemistry and Western blotting. Despite the presence of these antibodies, dystrophin-positive fibers were still present in grafted muscles 9 months after transplantation. Moreover, the muscles did not show massive infiltration by CD4 cells, CD8 cells, or macrophages, as already described in myoblast allotransplantations. This lack of rejection was attributed to the sequestrated nature of dystrophin after fiber formation. These results indicate that myoblast transplantation leads to fiber formation when immunocompetent but fully histocompatible donors and recipients are used and that dystrophin incompatibility alone is not sufficient to induce an immunological rejection reaction.

Animals↗
PubMed1995

FK506 immunosuppression to control the immune reactions triggered by first-generation adenovirus-mediated gene transfer.

Despite good initial success in vivo, gene transfer using first-generation replication-defective adenovirus has been reported to lead to transient reporter gene expression and to trigger inflammatory reactions in various organs and animal models. To gain more knowledge on this phenomenon, immune reactions were investigated following in vivo transfection of adult immunocompetent mouse muscle using a delta E1/E3a adenoviral vector encoding a beta-galactosidase (beta-Gal) expression cassette. Cellular and humoral immune reactions, and rejection of beta-Gal-positive muscle fibers, occurred within 3 weeks. The muscles showed massive infiltration by macrophages, natural killer cells, and CD8+ leukocytes. The mRNA levels of granzyme B and interferon-gamma were increased 6 days after vector injection, indicating that the infiltrating lymphocytes were activated. Antibodies were formed against the adenovirus group antigen and the beta-Gal gene product 2 weeks after construct injection. The immunosuppressant FK506, however, blocked the cellular infiltration and the humoral response and allowed strong, stable transgene expression over 1 month. These data emphasize the immune problems related to the use of delta E1/E3a adenoviruses as vectors for gene therapy, and they underline the potential of FK506 as an immunosuppressant adjunct treatment for adenovirus-mediated gene transfer.

Adenoviridae↗
PubMed1995

Simultaneous use of the PCR-SSCP method and immunohistochemistry for increasing the detection efficacy of p53 abnormalities in human lung cancer.

Malignant neoplasms possess multiple genetic abnormalities. Among those, p53 gene abnormalities are the most frequent in human neoplasms. To screen for p53 abnormalities, both immunohistochemistry (IHC) and the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) methods are commonly used, but neither can detect specimens simultaneously by the two methods, 12 abnormal cases (34%) were detected by IHC and 9 abnormal cases (26%) were detected by PCR-SSCP. Six abnormal (17%) and 20 normal (57%) cases showed concordant results between the methods, although 9 cases (26%) showed discordance, including 6 IHC-positive cases (17%) and 3 SSCP-positive cases (9%). Because it is known that some p53 abnormalities are detected only by IHC or only by PCR-SSCP, discordant cases should be assessed as possessing abnormalities. Fifteen cases (43%) were finally assessed as abnormal. These results suggest that the two methods together can increase the sensitivity of screening for p53 abnormalities.

Gene Expression↗
PubMed1994

Utilization of myoblasts from transgenic mice to evaluate the efficacy of myoblast transplantation.

A possible treatment for Duchenne muscular dystrophy is the injection of normal myoblasts into dystrophic muscles to induce the formation of new, healthy, and dystrophin-positive muscle fibers. To develop this therapy, it is important to identify the muscle fibers formed by the injected myoblasts in the host muscles. In this study, we used myoblasts from transgenic mice which have a gene expressing beta-galactosidase under the control of the promoter of quail fast skeletal muscle troponin I. This transgene is expressed in myotubes and muscle fibers, but not in myoblasts. Twenty-eight days after myoblast transplantation in nude and in mdx mice, muscle fibers containing of beta-galactosidase were identified by x-gal staining. In mdx mice, most of the beta-galactosidase-positive muscle fibers resulting from the myoblast transplantation were also dystrophin positive. This technique could make it possible to follow the success of myoblast transplantation even in mice that are not depleted of dystrophin.

Animals↗
PubMed1994

Very efficient myoblast allotransplantation in mice under FK506 immunosuppression.

Transgenic CD1 mice expressing beta-galactosidase were used as myoblast donors. The myoblasts were injected in normal or mdx muscles previously irradiated and injected with notexin. Twenty-eight days after myoblast transplantation, the percentage of muscle fibers beta-glactosidase-positive was low in mice not immunosuppressed but was high (80%) in those treated with FK506. In mdx mice, muscle fibers expressing beta-galactosidase were also dystrophin positive. Most of the mice not treated with FK506 produced antibodies against the donor myoblasts. These results indicate that FK506 is a very useful immunosuppressive drug for myoblast transplantation in mice. Irradiation and notexin injection used in our experiments are, however, not feasible in humans. Other manipulations capable of increasing the participation of donor myoblasts to regeneration will therefore have to be identified before new clinical trials are attempted.

Animals↗
PubMed1994

Abnormal p53 expression in human lung cancer is associated with histologic subtypes and patient smoking history.

Among the most common mutations in human lung cancer are those affecting the p53 gene. The expression of p53 in the nucleus is considered an immunohistochemical reflection of the nuclear accumulation of mutant p53 protein, which is coded by the p53 gene with missense mutation and has a prolonged half-life. In the present study, p53 expression detected by means of immunohistochemistry occurred frequently in human lung cancer and was associated with histologic subtypes. The alteration in the p53 gene was found to be a relatively early genetic event in the development and progression of lung cancer and to be maintained in the process of metastasis: abnormal p53 expression was found in both the early and late clinical stages, and identical p53 expression was detected consistently among primary and metastatic lesions from the same patients. Furthermore, an observed association between abnormal p53 expression and the patients' smoking history suggests that the p53 gene could be a common target of tobacco-associated carcinogenesis in lung cancer.

Carcinoma, Non-Small-Cell Lung↗
PubMed1994

Antiarrhythmic effects of eicosapentaenoic acid during myocardial infarction--enhanced cardiac microsomal (Ca(2+)-Mg2+)-ATPase activity.

The effects of dietary supplementation with eicosapentaenoic acid (EPA) on ventricular arrhythmias during myocardial infarction were examined in a canine model. EPA was incorporated into cellular membranes after ingestion of EPA-ester (100 mg/kg body weight/day) for 8 weeks. The ratio of EPA to arachidonic acid (AA) in platelet cell membranes and myocardial microsomes was significantly increased (7% to 37% in platelet cell membranes; p < 0.01, 3% to 12% in non-infarcted cardiac microsomes; p < 0.01, and from 2% to 8% in infarcted cardiac microsomes; p < 0.01). Dietary supplementation with EPA significantly reduced the incidence and severity of arrhythmias during coronary artery occlusion. Immediately after coronary artery occlusion, all of the animals in the control group that were given a toxic dose of digitalis developed ventricular tachycardia (VT) or ventricular fibrillation (Vf), whereas none of the animals in the EPA-supplement group developed VT or Vf within 15 min after administration of digitalis. Regardless of the presence of an infarcted area, the specific activity of the Ca(2+)-pump enzyme ((Ca(2+)-Mg2+)-ATPase) within the myocardial microsomal fraction of the EPA-supplemented group was significantly higher than in that of the control group (Vmax: 140.5 +/- 19.1 vs 94.8 +/- 28.9 nmol/mg/min in non-infarcted cardiac microsomes, p < 0.01, 130.9 +/- 18.4 vs 90.2 +/- 26.4 nmol/mg/min in infarcted cardiac microsomes, p < 0.01, EPA vs control group, respectively). The specific activities of the Na(+)-pump enzyme ((Na(+)-K+)-ATPase) and NADPH-dependent cytochrome C reductase in infarcted and non-infarcted cardiac microsomes did not differ between these groups. These results indicate that EPA supplementation increases the (Ca(2+)-Mg2+)-ATPase activity within myocardial membranes that is involved in Ca2+ metabolism in myocardial cells by increasing the ratio of EPA to AA within cellular membranes. These cellular alterations are likely to reduce the severity of ventricular arrhythmias by inhibiting the rapid accumulation of intracellular Ca2+ following ischemia.

Animals↗
PubMed1993

Immunoaffinity purification of prostaglandin E2 and leukotriene C4 prior to radioimmunoassay: application to human synovial fluid.

When human synovial fluid as such was subjected to radioimmunoassays of prostaglandin E2 (PGE2) and leukotriene C4 (LTC4), there was no linear increase in PGE2 and LTC4 as the amount of synovial fluid was raised. For removal of substances thus disturbing the assay we developed a method of immunoaffinity purification of PGE2 and LTC4. A monoclonal antibody against PGE2 or LTC4 was coupled to BrCN-activated Sepharose 4B. When synovial fluid mixed with radiolabelled PGE2 or LTC4 was applied to the column of immobilized antibody, the ligand was adsorbed to the column and eluted with a mixture of methanol/water in a recovery of about 80%. The purified material showed a linearity between the amount of the sample and the value of radioimmunoassay. The one-step method was applied to synovial fluid from patients with rheumatoid arthritis, osteoarthritis and other joint diseases.

Animals↗
PubMed1993

[Effects of polychlorinated biphenyls on regeneration of the peripheral nerve in rats].

The sciatic nerves was crushed at the mid-thigh level on the last day of 32 days oral administration of PCB. Nerve specimens were obtained from the crushed regions at 1, 2, 4 and 8 weeks after crushing. There was no significant difference between the experimental group and the control group in the density of regenerating fibers and distribution of fiber diameters at 1 and 2 weeks. At 4 and 8 weeks, however, the density of myelinated fibers was higher in the experimental group than in the control group. These results indicate that PCB may inhibit the regeneration of the crushed nerves. It is, however, still unknown that this adverse effects of PCB on the peripheral nerve depends on the disturbance of the remyelination or regeneration of the axon or both.

Animals↗
PubMed1992

Tumour angiogenesis in prostatic carcinoma with and without bone marrow metastasis: a morphometric study.

One hundred and one cases of clinical prostatic carcinoma (PCa), primary site, were analysed to define the interrelationship between tumour angiogenesis, histological grade, and bone marrow metastasis. Tumour angiogenesis was determined by the blood capillary density ratio (BCDR; a/b), defined as the ratio between the area of the blood capillaries (a) and the area of the tumour (b). The BCDR was evaluated by a colour image analysis system employing a computerized morphometrical method. A total of 43 cases of PCa with bone marrow metastasis (stage D2) and 58 cases of PCa without metastasis (stage B, C) were utilized. The prostatic carcinomas were classified into three groups (low, intermediate, and high) using Gleason's grading system. The BCDR of the primary PCa with bone marrow metastasis was similar in each of the three histologically graded scores. On the other hand, in the cases of PCa without metastasis, the BCDR of high score PCa was higher than those of the low and intermediate score PCa (U-test; P < 0.001). The BCDR of the high score PCa without metastasis was similar to that of the PCa with bone marrow metastasis. The BCDR may provide help in predicting tumour progression with regard to bone marrow metastasis of PCa with low and intermediate Gleason's scores.

Bone Marrow↗
PubMed1992

Acute myocardial infarction in a young adult as possible sequela of Kawasaki disease--a case report of successful intracoronary thrombolytic therapy and histological study of an aneurysm.

Emergency coronary angiography in a 28-year-old male suffering an acute anteroseptal myocardial infarction revealed complete obstruction of the left anterior descending artery in association with multiple aneurysms of the 3 major coronary arteries. Successful intracoronary thrombolytic treatment with urokinase infusion directly into the infarct-related artery was performed 2 h after the onset. Follow-up left ventriculogram showed preservation of left ventricular wall motion. Fifty days after the infarction, he underwent aorto-coronary bypass surgery. Histological examination of the biopsy specimen obtained from the aneurysm of the distal portion of the right coronary artery revealed that the 3-layer architecture of the arterial wall had been completely lost. The wall was replaced by fibrotic tissue, with slight mononuclear cell infiltration around the small vessels, but no acute inflammatory reaction or atheromatous change was seen. In spite of the presence of the coronary risk factors of hypertension and hyperlipidemia, angiography revealed no evidence of atherosclerosis of systemic arteries. It is suggested that the coronary aneurysms in this case are possible sequelae of Kawasaki disease in childhood.

Adult↗
PubMed1992

Remarkable increase in CD26-positive T cells in patients with human T lymphotropic virus type I (HTLV-I) associated myelopathy.

We used two-color flow cytometric analysis to investigate CD26+ (Ta1+) cells in peripheral blood T lymphocytes from patients with human T-lymphotropic virus type-I (HTLV-I)-associated myelopathy (HAM). The percentage of CD26+ cells among CD3+ cells was markedly increased in patients with HAM, compared with anti-HTLV-I seropositive carriers (p < 0.001) and seronegative controls (p < 0.01). Within the subpopulation of T cells, a significantly high percentage of CD26+ cells was detected in both CD4+ and CD8+ cell populations. Furthermore, analysis of HLA-DR+ T cells revealed similar results. In contrast CD4+CD45RA+ cells were significantly decreased in comparison with controls. These results suggest that immunologically activated or memory T cells found in peripheral blood may be etiologically relevant to HAM.

Adult↗
PubMed1992

[A case of foreign-body granuloma treated with steroid hormone].

A 68-year-old woman was admitted to Nagasaki University Hospital complaining of gait disturbance. She had suffered from hemifacial spasm since the age of 56 and had undergone neurovascular decompression for the spasm in another hospital five years before admission. At surgery, the vertebral and posterior inferior cerebellar arteries had been separated from the facial nerve with cotton string and attached to the clivus with alpha-cyanoacrylate monomer. Although the hemifacial spasm had improved postoperatively, the patient had suffered from gait disturbance and headache for two months after surgery, and hearing disturbance and hemifacial palsy on the same side as the hemifacial spasm for seven months after surgery. At the time of the present admission, contrast-enhanced CT scan revealed a mass at the left cerebello-pontine angle. In the T1-weighted inversion recovery sequence of MRI, the mass showed a slightly lower intensity than that of surrounding tissues. In the T2-weighted spin echo sequence of MRI, it showed a heterogenously low intensity with some high intensity spots. We diagnosed this mass as a foreign-body granuloma and treated it with dexamethasone injected intramuscularly. Edema decreased around the granuloma, and her gait disturbance improved markedly. But the hearing disturbance and hemifacial palsy did not improve at all, indicating that these two symptoms might not be caused only by brain edema but also by direct damage due to granuloma or inflammation. We thought that the steroid hormone elicited good results in the treatment of inoperable foreign-body granuloma.

Aged↗