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Biomedical subjects

K Ikeuchi

Publications and source records attributed to K Ikeuchi.

At least 55 records · Page 3Linked to original sources

Mechanical effects of a cushioned plate on bone fixation.

In vitro and in vivo experiments were carried out to study mechanical effects of the cushioned plate fixation in which a cushion was placed between a metal plate and bone. The cushioned plate fixation was found to be flexible in the physiological stress range and to reduce the stick slip between bone and the plate. A blood-soaked compression test indicated that the cushion moderates the stress shielding effect which occurs in the vicinity of the rigid plate, this being consistent with the result of in vivo experiments.

Animals↗

Human immunodeficiency virus infection of human bone marrow stromal fibroblasts.

The human immunodeficiency virus (HIV) preferentially infects CD4 positive T cells and monocytes. Other human cell types have been reported to be infectable with HIV, including cells of mesenchymal origin. In this report, we show that both primary human bone marrow stromal fibroblasts and an immortalized human stromal fibroblast line are susceptible to HIV infection. These cells are capable of passing HIV to cells of lymphoid or myeloid lineage, and may thereby act as a reservoir of virus. This in vitro system may be a useful model for assessing the pathophysiology of hematopoietic dysfunction in AIDS patients.

Actins↗

Development of an artificial articular cartilage.

We have attempted to develop an artificial articular cartilage on the basis of a new viewpoint of joint biomechanics in which lubrication and load-bearing mechanisms of natural and artificial joints are compared. We investigated poly(vinyl alcohol)-hydrogel (PVA-H) which has been recognized as a rubber-like gel and have improved the mechanical properties of this gel through a new synthetic process. In this article we report the biocompatibility and various mechanical properties of the new, improved PVA-H from the aspect of its usefulness as artificial articular cartilage. As regards the lubrication, we measured the change of thickness and fluid pressure of the gap formed between a glass plate and the specimen under loading and found that the PVA-H had a thicker fluid film under higher pressure than polyethylene (PE). The momentary stress transmitted through the specimen revealed that PVA-H had a lower peak stress and a longer duration of sustained stress than PE, suggesting a better damping effect. The wear factor of PVA-H was approximately five times as large as that of PE. Histological findings of the articular cartilage and synovial membranes around the PVA-H implanted for 8-52 weeks showed neither inflammatory nor degenerative changes. The PVA-H artificial articular cartilage could be attached to the underlying bone using an osteochondral composite material. Although there remain still some problems to solve, PVA-H seems to be a very interesting and promising material which meets the requirements of artificial articular cartilage.

Animals↗

Factors affecting cellular tropism of human immunodeficiency virus.

To evaluate the basis of the slow growth of many human immunodeficiency virus strains in monocytes/macrophages, various stages of the virus life cycle have been studied for their possible contribution to viral tropism. Although we found that monocytic U937 cells had a higher percentage of CD4-positive cells than T-lymphoid H9 cells, the human immunodeficiency virus strain grew much less efficiently in the monocytic line. Viral tropism was primarily determined during the early stages of the virus cycle, that is, sometime between binding of the virus to the cell surface and reverse transcription of viral genomic RNA. Once the virus entered the host cell, reverse transcription, use of the long terminal repeat, RNA expression, and production of virus particles was about as efficient in monocytes as in T cells. Thus, during viral entry into the host cell cytoplasm there is a major limiting event that is particularly inefficient in U937 cells and possibly in all monocytes/macrophages.

CD4 Antigens↗

Infection of nonlymphoid cells by human immunodeficiency virus type 1 or type 2.

Human epithelial cells (L132) derived from embryonic lung and human lung fibroblasts (MRC5) were infected by human immunodeficiency virus type 1 (HIV-1) or type 2 (HIV-2). Surface CD4 protein was detected on these cells, and recombinant soluble CD4 (sCD4) blocked infection, indicating that HIV infection was mediated by the cell surface CD4 protein. In contrast, infection of human primary chondrocyte cells (C23), synovial cells (HSA), and foreskin fibroblasts (F13) was apparently independent of cell CD4-mediated mechanisms. Surface CD4 protein could not be detected on these cells, and sCD4 did not block the infection. F13 cells could be infected only by HIV-2, not by HIV-1, under our experimental conditions. In cells of mesenchymal orgin, viral production could be detected only after cocultivation with the human T-lymphoid H9 cells but not by conventional viral assays, including reverse transcriptase and p24 antigen assays in cell culture supernatant and immunofluorescence of host cells. Our DNA transfection studies indicated that this lack of detectable viral production was not due to the inefficient use of the HIV long terminal repeat or the Tat protein in these cells. These mesenchymal and epithelial cells were susceptible to HIV infection but differed in mechanism of virus entry compared with hematopoietic cells such as T lymphocytes. These observations may provide insights into clinical syndromes such as lung dysfunction in HIV-infected newborns and connective tissue disorders in HIV-infected adults.

Antigens, CD↗

Immunologic effects of recombinant interferon-gamma in patients with renal cell carcinoma.

Immunologic and antitumor effects of human recombinant interferon-gamma were studied in patients with renal cell carcinoma. A daily dose of 6 to 12 x 10(6) units/m2 of interferon-gamma was given by intravenous drip infusion or intramuscular injection to nine patients over a period varying from two to 16 weeks. Antibody-dependent cell-mediated cytotoxicity and OKIa1-positive monocytes count increased significantly after the therapy was started. Interferon-gamma transiently increased OKT3- and OKT4- positive lymphocyte count. Tumor regression was not observed when clinical response was evaluated in seven patients. Two others, who had no measurable metastases, were not evaluated, because interferon-gamma were given to them as post-operative adjuvant therapy. Our results indicate that interferon-gamma stimulated monocytes and enhanced cell-mediated cytotoxicity; they also suggest the necessity of combining monoclonal antibodies and other biological response modifiers that effect tumor-associated antigens.

Adult↗

[Replacement of superior vena cava with resection of Hodgkin's disease of the thymus: a case report].

A 31-year-old male was diagnosed to have malignant thymoma with superior vena cava occlusion. At operation, we performed extended resection of tumor and superior vena cava, and replacement with ringed PTFE graft. Histological diagnosis was nodular sclerotic type of Hodgkin's disease of thymus. He received radiation with Liniac and chemotherapy post operatively, and post operative venography revealed graft patent. He is doing well 3 years after surgery.

Adult↗

Lack of a negative influence on viral growth by the nef gene of human immunodeficiency virus type 1.

Human immunodeficiency virus type 1 (HIV-1) contains an open reading frame called nef at the 3' end of its genome. The nef gene product has been reported to down-regulate viral growth by suppressing viral transcription through interaction with the long terminal repeat region. We have compared two isogenic HIV-1 (HIV-1-WI3) strains, one of which lacks nef expression, and found little difference between them in in vitro growth. We tested effects on viral entry, DNA synthesis, and RNA expression by measuring HIV-specific low molecular weight DNA and RNA after infection. The qualitative and quantitative aspects of DNA and RNA synthesis were comparable between the nef+ and nef- strains. The effects on viral growth were also examined by following changes in reverse transcriptase activity during the course of infection. The presence of the nef gene product failed to slow viral growth in several different cell types tested, including the human T-lymphocyte cell lines H9 and CEM-SS, human primary T cells enriched for CD4+ cells, and human monocytic cell lines U-937 and THP-1. On the contrary, the nef+ strain grew more efficiently in some cell types than the nef- strain. The same results were obtained with nef+ and nef- strains of a different virus, HIV-1-432, whose Nef had been reported to have a negative effect on viral growth. Our data suggest that the Nef protein does not act as a negative factor, at least in the experimental systems employed in our studies.

Cell Line↗

CD4+ lymphocyte function with early human immunodeficiency virus infection.

The pathogenesis of cellular immune deficiency following human immunodeficiency virus (HIV) infection could result from quantitative and/or qualitative dysfunction of the CD4+ lymphocyte population. To better characterize the T-cell response to soluble antigen with HIV infection, we have isolated peripheral blood lymphocytes and purified populations of CD4+ lymphocytes from healthy HIV antibody-positive subjects, patients with acquired immunodeficiency syndrome (AIDS)-related complex (ARC), and healthy HIV antibody-negative controls. T-lymphocyte function was determined by proliferative response to lectin (phytohemagglutinin), phorbol 12-myristate 13-acetate (PMA), calcium ionophore, purified recombinant HIV envelope gp120, tetanus toxoid antigen, and tetanus toxoid antigen in the presence of recombinant gp120 or purified recombinant soluble CD4. PBLs and CD4+ lymphocytes from asymptomatic HIV-infected subjects responded equally well to lectin, PMA, and/or calcium ionophore and to tetanus toxoid as cells from uninfected control subjects. The cells that proliferated in response to a soluble antigenic stimulus did not respond to gp120. Cells from subjects with ARC had a selective antigen recognition defect independent of the number of CD4+ lymphocytes. Recombinant gp120 inhibited CD4+ lymphocyte proliferation to antigenic stimulus by 30-40%. Recombinant soluble CD4, a proposed therapeutic for HIV, had no effect on T-cell response to antigen. A selective antigen recognition response was not compromised early in HIV infection but was compromised in subjects with ARC. Inhibition of proliferation to tetanus toxoid by gp120 suggests that HIV may affect major histocompatibility complex II restricted antigen recognition independent of CD4+ cell loss.

AIDS-Related Complex↗

Natural killer cell activity and recycling capacity of natural killer cells in patients with carcinoma of the prostate.

Natural killer (NK) cell activity and recycling capacity of NK cells in patients with carcinoma of the prostate (CaP) was determined by combining the 51Cr-release cytotoxicity assay and single cell cytotoxicity assay in agarose. The NK cell activity in patients with advanced CaP (stage D) was significantly lower than the NK cell activity of normal controls and that of patients with localized CaP (stage B and C). The number of active NK cells in the peripheral blood lymphocytes was similar in all groups tested including normal controls, patients with localized CaP, and patients with advanced CaP. Maximal killing potential (Vmax) and maximal recycling capacity (MRC) were significantly reduced in patients with advanced CaP as compared to patients with localized CaP or normal controls. Obtained results indicated that the depressed NK cell activity in advanced CaP was not due to a reduced number of active NK cells but due to the decreased recycling capacity of the individual NK cells.

Adult↗

Heme metabolism and turnover of cytochrome P-450 in tumor-bearing mouse livers.

Hepatic heme metabolism and in vitro translation of poly(A) + RNA from livers were studied to elucidate the mechanism of the reduction of microsomal cytochrome P-450 in tumor-bearing mouse livers. Hepatic delta-aminolevulinic acid synthase activity in male C57BL/6N mice (0.203 nmol/mg protein/h) at 8 days after the transplantation of Ehrlich ascites tumor cells was the same level as that of normal livers (0.206 nmol/mg protein/h). On the other hand, hepatic heme oxygenase activity of tumor-bearing mice (0.482 nmol/mg protein/10 min) had increased 8 days following i. p. transplantation of tumor cells when compared with that of normal mouse livers (0.296 nmol/mg protein/10 min). SDS-gel electrophoresis of in vitro translation products of poly(A) + RNA extracted from membrane-bound polysomes of the livers from tumor-bearing mice showed no significant differences from that of normal controls in the region of cytochrome P-450, that is, the molecular weight region of Mr = 47,000-60,000, although microsomal protein content in this region estimated by Coomassie-blue staining was reduced. These results suggest that the decrease of heme biosynthesis or the translation of cytochrome P-450 mRNA played a very small part in the reduction of microsomal cytochrome P-450 in tumor-bearing mice.

5-Aminolevulinate Synthetase↗

Changes in brush-border enzyme activities of intestinal epithelial cells isolated from the villus-crypt axis during the early phase of alloxan diabetes in rats.

The sucrase activity in enterocytes isolated from the villus crypt axis was found to increase in all regions of the villus from day 2 after induction of diabetes, and the increase continued until day 4. In contrast, alkaline phosphatase activity increased mainly in the apical one-third of the villus-crypt column, and the increase occurred abruptly on day 4 with increase in food intake.

Alkaline Phosphatase↗

Fatty acid composition and Shwartzman activity of lipopolysaccharides from oral bacteria.

The composition and the nature of the linkage of fatty acids and the Shwartzman activity of lipopolysaccharide (LPS) preparations derived from oral gram-negative bacteria including Bacteroides gingivalis, Bacteroides loesheii, Eikenella corrodens, Fusobacterium nucleatum, and Actinobacillus actinomycetemcomitans were examined. 3-Hydroxylated and nonhydroxy fatty acids of various chain lengths were found in all of the LPS preparations. All nonhydroxy fatty acids were found to be ester-bound, and part of the 3-hydroxy fatty acids in the LPS of B. gingivalis, E. corrodens, F. nucleatum, and A. actinomycetemcomitans were shown to be involved in ester linkage. It was also suggested that the hydroxy group of the ester-bound 3-hydroxy fatty acid of the LPS of F. nucleatum and A. actinomycetemcomitans is at least partly substituted by another fatty acid, but in the LPS of B. gingivalis and E. corrodens it is not. The main amide-linked fatty acid of the LPS of B. gingivalis, E. corrodens, F. nucleatum, and A. actinomycetemcomitans was 3-hydroxyheptadecanoic, 3-hydroxydodecanoic, 3-hydroxyhexadecanoic, and 3-hydroxytetradecanoic acid, respectively. The results of the Shwartzman assay showed that the E. corrodens LPS was the most active among the preparations tested, and that the Shwartzman toxicity of Bacteroides LPS is extremely low.

Actinobacillus↗

Isolation of immunochemically distinct form of cytochrome P-450 from microsomes of tulip bulbs.

A highly purified cytochrome P-450 was obtained from the microsomes of tulip bulbs (Tulipa gesneriana L.). The molecular weight (Mr = 52,500) and amino acid composition of this plant cytochrome P-450 are similar to those reported for rat livers. On the contrary, Ouchterlony double diffusion analyses indicated that cytochrome P-450 isolated from tulip bulbs shares no common antigenic determinants with those of 9 other plants, in spite of the presence of comparable contents of cytochrome P-450 and/or trans-cinnamate 4-monooxygenase with tulip bulbs.

Amino Acids↗

Altered distribution of constitutive forms of microsomal cytochrome P-450 in tumor-bearing mouse liver.

Changes of microsomal cytochrome P-450 species in the livers of mice were examined after the inoculation of Ehrlich ascites tumor cells i.p. into male ddY mice. The total content of hepatic cytochrome P-450 was observed to decrease around 6 days after the tumor-inoculation and reached the level of 40 to 50% of those of control mice (27.8 nmol P-450/g of control liver) after 10 days, while the liver weights of tumor-bearing mice slightly increased even at the end of the 2nd week. Microsomal proteins of tumor-bearing mice remained at the level of around 80% of control livers at the end of the 2nd week. The activity of 7-ethoxycoumarin deethylation decreased roughly in proportion to the content of microsomal cytochrome P-450. On the contrary, the specific activity of benzphetamine N-demethylase per nmol of P-450 in the tumor-bearing mouse liver increased to more than 2 fold of the value of normal liver (25 nmol HCHO/nmol P-450/min for control liver) during the last stage of the second week. These results suggest that the reduction of individual forms of cytochrome P-450 in the tumor-bearing mouse liver was not random and a new steady state of distribution of these hemeproteins was established under the pathological conditions.

7-Alkoxycoumarin O-Dealkylase↗