Method for assessment of competency to consent in the mentally ill. Rationale, development, and comparison with the medically ill.
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Comprehension↗
Biomedical subjects
F Kitamura
Publications and source records attributed to F Kitamura.
Intracellular Signal-transducing elements involved in transendothelial migration of lymphoma cells.
To investigate the molecular mechanisms underlying transendothelial migration of tumor cells, an essential process for their hematogenous dissemination, we developed an in vitro model system that allows the separate monitoring of cell adhesion and transmigration processes. This system uses a human pre-B lymphoma cell line, Nalm-6, and a cultured mouse endothelial cell line, KOP2.16. Nalm-6 cells rapidly adhered to KOP2.16 and subsequently transmigrated underneath them. Using this model, we examined the effects on transendothelial migration, of various reagents which specifically interfere with the function of intracellular signal transduction molecules. Treatment of Nalm-6 cells with wortmannin (WMN), herbimycin A, pertussis toxin, or C3 exoenzyme of Clostridium botulinum, which specifically inhibit P13 kinase and/or myosin light chain kinase, herbimycin-sensitive tyrosine kinases, heterotrimeric G proteins, and the small G proteins, and the small G proteins rho/rac, respectively, reduced transmigration in a dose-dependent manner, Pretreatment of KOP2.16 endothelial cells with WMN also reduced transmigration in a dose-dependent manner. Binding of Nalm-6 binding to KOp2.16 was not affected, even when Nalm-6 or KOP2.16 cells were pretreated with these inhibitors, indicating that the reduction of transmigration was not due to a reduction of Nalm-6 to KOP2.16. These results also indicate that the signal transduction pathway(s) involved in transmigration can be dissociated from that of adhesion. Our results support the notion that endothelial cells are not a passive barrier in lymphoma extravasation, but that they assist lymphoma cell extravasation.
Androstadienes↗
Assessment of mutations of Ha- and Ki-ras oncogenes and the p53 suppressor gene in seven malignant mesothelioma patients exposed to asbestos--PCR-SSCP and sequencing analyses of paraffin-embedded primary tumors.
To examine whether malignant mesothelioma due to asbestos has genetic alterations in the Ha- and Ki-ras oncogenes or in the p53 suppressor gene, we analyzed the point mutations of these genes in paraffin-embedded autopsy samples of the primary tumors of malignant mesothelioma in seven asbestos patients who died from malignant mesothelioma. The genetic analysis was conducted by the polymerase chain reaction-single strand comformation polymorphysms (PCR-SSCP) method in all patients, and through the sequencing of deoxyribonucleic acid (DNA) bases in one patient. No genetic alterations were found in exons 1 or 2 of Ha- and Ki-ras oncogenes, or in exons 5 to 9 of the p53 gene, in any of the patients. Further studies on a larger number of patients are required to reach a definite conclusion concerning the genetic effects of asbestos on malignant mesothelioma.
Aged↗
Widespread expression of chondroitin sulfate-type serglycins with CD44 binding ability in hematopoietic cells.
Serglycin is a family of small proteoglycans with Ser-Gly dipeptide repeats and is modified with various types of glycosaminoglycan side chains. We previously demonstrated that chondroitin sulfate-modified serglycin is a novel ligand for CD44 involved in the adherence and activation of lymphoid cells. In this study, we investigated the production and distribution of CD44 binding serglycins in various hematopoietic cells and characterized their carbohydrate side chains. Immunoprecipitation analysis using CD44-IgG and polyclonal antibody against the serglycin core peptide demonstrated that various serglycin species capable of binding CD44 are produced by a variety of hematopoietic cells including lymphoid cells, myeloid cells, and a few tumor cell lines. Glycosaminoglycans on these serglycins, which are essential for CD44 binding, are composed of chondroitin 4-sulfate or a mixture of chondroitin 4-sulfate and chondroitin 6-sulfate, but no heparin or heparan sulfate side chain was detected. The serglycins are also secreted by normal splenocytes, lymph node lymphocytes, and bone marrow cells, whereas they are secreted in very small amounts by normal thymocytes. Secretion of serglycins is greatly enhanced by mitogenic stimulation with concanavalin A or lipopolysaccharide. Our results showed that serglycin, unlike hyaluronate, is produced and secreted in a functional (CD44 binding) form by many members of the hematopoietic system including various lymphocyte subsets. Our data suggest that serglycin may serve as a major ligand for CD44 in various events in the lymphohematopoietic system.
Animals↗
Validity and reliability of Structured Interview for Competency Incompetency Assessment Testing and Ranking Inventory.
The Structured Interview for Competency and Incompetency Assessment Testing and Ranking Inventory (SICIATRI) is a structured interview guide to assess the competency for giving informed consent to treatment among psychiatric and medical patients. The competency levels of 48 psychiatric and medical inpatients were assessed by SICIATRI. A relatively high- inter-rater reliability of the SICIATRI items (over half of the items had kappa > or = .60) and concurrent validity (sensitivity = .83, specificity = .67 as measured against the global judgement of competency rating by the attending physician) were obtained. In addition to its brevity (it takes about 20 minutes to complete), these findings may warrant application of this instrument in a clinical setting.
Adult↗
The Ig alpha/Igbeta heterodimer on mu-negative proB cells is competent for transducing signals to induce early B cell differentiation.
The immunoglobulin alpha (Ig alpha)/Ig beta heterodimer was detected on the surface of mu-negative proB cell lines in association with calnexin. The cross-linking of Ig beta on proB cells freshly isolated from bone marrow of recombination activating gene (RAG)-2-deficient mice induced a rapid and transient tyrosine-phosphorylation of Ig alpha as well as an array of intracellular proteins including Syk, PI3-kinase, Vav, and SLP-76. It also elicited the phosphorylation and activation of a MAP kinase ERK but not JNK/SAPK or p38. When RAG-2-deficient mice were treated with anti-Ig beta monoclonal antibody, developmentally arrested proB cells were induced to differentiate to the small preB cell stage as observed when the mu transgene was expressed in RAG-2-deficient mice. Thus, the cross-linking of Ig beta on proB cells appears to elicit differentiation signals analogous to those delivered by the preB cell receptor in normal B cell development.
Animals↗
The roles of preB cell receptor in early B cell development and its signal transduction.
The preB cell receptor is expressed for a short period after mu heavy chain is produced, that is, at the large preB cell stage in B cell development. The severe impairment of B cell differentiation observed in mice deficient for the preB cell receptor clearly demonstrated the importance of the preB cell receptor in B cell development. Analyses of bone marrow precursor B cells in normal and B cell-deficient mutant mice indicated the preB cell receptor transduced signals to drive cell cycle and to induce allelic exclusion. The proliferation of the preB cell receptor-expressing cells leads to the selective expansion of cells which have succeeded in the productive rearrangement of mu heavy chain gene. This process builds up a preB cell pool large enough to generate sufficient numbers of mature B cells. The preB cell receptor appears to induce allelic exclusion by shutting off the expression of recombinase activation gene (RAG). In order to analyse the signal transduction pathway downstream of the preB cell receptor, we have developed a new system in which cross-linking of Ig beta expressed on bone marrow proB cells mimics the signalling through the preB cell receptor to induce differentiation from proB to small preB cells.
Alleles↗
[Rheumatic valvular heart disease].
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Aortic Valve Insufficiency↗
A novel ligand for CD44 is serglycin, a hematopoietic cell lineage-specific proteoglycan. Possible involvement in lymphoid cell adherence and activation.
The lymphocyte adhesion molecule CD44 recognizes a non-hyaluronate proteoglycan, gp600, secreted by mouse T cell line CTLL2. We now demonstrate that gp600 is identical to serglycin, a member of the small proteoglycan family stored in intracellular secretory granules of lymphoid, myeloid, and some tumor cells. Purified gp600 has the ability to bind specifically to CD44, and the binding is dependent on activation of CD44. The CD44-binding elements on gp600 or serglycin are glycosaminoglycans consisting of chondroitin 4-sulfate. Serglycin is readily exocytosed, and its interaction with active form CD44 augments the CD3-dependent degranulation of CD44 positive CTL clones. We conclude that the serglycin secreted from secretory granules of hematopoietic cells is a novel ligand for CD44, and could regulate lymphoid cell adherence and activation.
Amino Acid Sequence↗
Dysregulated expression of the IL-2 receptor beta-chain abrogates development of NK cells and Thy-1+ dendritic epidermal cells in transgenic mice.
The IL-2 receptor beta-chain (IL-2R beta), a specificity-determining subunit in the IL-2R complex with a restricted tissue distribution pattern, is essential for signal transduction. Our previous studies demonstrate that the continuous treatment of mice with anti-IL-2R beta resulted in the complete disappearance of NK cells and Thy-1+ dendritic epidermal cells (Thy-1+ dEC), suggesting that signals through IL-2R beta are critically involved in development of these lymphocyte subsets. However, these lymphocyte subsets are reported to be apparently unaffected in the IL-2-deficient mice. To further examine the biological roles of the IL-2R beta, transgenic mice carrying the IL-2R beta transgene were generated. In these mice, high levels of the cell surface expression of the IL-2R beta were observed in essentially all hematopoietic lineage cells, and CD4+ T cells as well as CD8+ T cells showed vigorous cell proliferation upon IL-2 stimulation. Surprisingly, NK cells marked with a high expression of NK1.1 in the spleen and Thy-1+ dEC in the skin were completely absent in transgenic mice. However, the development of other lymphocyte subsets including conventional alpha beta TCR+ cells, gamma delta TCR+ cells and B cells remained apparently intact. From these observations together with previous data on IL-2-deficient mice, we speculate that factors, other than IL-2 that utilizes the IL-2R beta as its functional receptor subunit, may have a vital role in the development of NK cells and Thy-1+ dEC. Implications for possible in vivo functions of over-expressed IL-2R beta are discussed.
Animals↗
Influence of looking at hazard lights on car-driving performance.
The purpose of the present study was to determine what effect (if any) looking at an automobile's hazard lights has on the direction in which a car is driven. Eight Japanese drivers participated in this experiment. Analysis indicated that (a) at night drivers passed closer to a forward-facing stationary car than during the day and (b) when instructions were given to look at the hazard lights of a forward-facing stationary car, drivers passed closer than when no such instructions were given or when the hazard lights were off. The relationship between looking at the visible targets in a visually poor environment and the direction in which a car is driven was discussed.
Adult↗
[A case of traumatic intrapulmonary foreign body].
A case of 60-year-old man with traumatic intrapulmonary foreign body that was not inhaled, but through the chest wall was described. In July 1992 a grass cutter was working in a forestry with a circular saw when he was struck into the right lung. He had a sharp pain in the anterior chest. No abnormality was seen in front of his neck and the chest wall. The next month he developed a cough with bloody sputum. The chest X-ray showed a metallic foreign body at the right side of manubrium. Computed tomogram showed a steel wire fragment lodging beside the innominate artery and vein and in the right lung. Median sternotomy was performed and a foreign body was successfully removed with partial resection of upper lobe.
Foreign Bodies↗
Selective long-term elimination of natural killer cells in vivo by an anti-interleukin 2 receptor beta chain monoclonal antibody in mice.
The interleukin 2 receptor beta chain (IL-2R beta) is preferentially expressed in natural killer (NK) cells, but is not detected in a majority of resting T and B cells. We recently established a novel monoclonal antibody (mAb) to murine IL-2R beta and examined in vivo the effect of the mAb in mice. We found that intraperitoneal injection of the anti-IL-2R beta mAb into adult mice resulted in a selective in vivo elimination of splenic NK function in various mouse strains. The reduction of NK cell function is associated with complete disappearance of NK1.1+ cells in C57BL/6 mice. Other lymphocyte subsets in the thymus and spleen were uncompromised. T cell function was not affected by the mAb treatment as judged by allogeneic cytotoxic T cell induction. The single injection of anti-IL-2R beta mAb caused a long-term elimination of splenic NK cells, lasting for at least 5 wk. We also found that NK and/or NK precursor cells become susceptible to the mAb treatment only after birth, suggesting that functional maturation of NK cells in terms of IL-2R beta expression is a later event in the course of NK cell development. The use of the anti-IL-2R beta mAb will be useful in defining the physiological role of NK cells in host defense as well as dissecting their developmental pathway in vivo.
Animals↗
Generation and characterization of monoclonal antibodies against rabbit CD4, CD5 and CD11a antigens.
We describe in this report the production and characterization of monoclonal antibodies (mAb) to the rabbit homologues of CD4, CD5 and CD11a antigens, and their use for phenotypic analysis of rabbit lymphoid cell lines. All the mAbs were produced by immunizing mice with rabbit thymocytes. mAb KEN-4 apparently identified rabbit CD4, precipitated two bands of 42 and 50 kDa under reducing and non-reducing conditions and markedly inhibited allo-MLR. The distribution of antigen-positive cells were restricted to the thymus and classical T-dependent areas in peripheral lymphoid tissues. mAb KEN-5 apparently identified rabbit CD5, precipitated a single polypeptide of 67 kDa similar to other anti-CD5 mAb in the human and mouse. The use of this mAb revealed that CD5+ B cells were infrequent in this species. mAb KEN-11 apparently identified rabbit CD11a and precipitated a heterodimer of 150/95 kDa by selectively recognizing the 150 kDa moiety. It blocked cation-dependent aggregation of phorbol ester-induced rabbit Con A blasts and also allo-MLR in a similar manner to other anti-CD11a mAb in various animal species. Phenotypic examination of HTLV-1 transformed rabbit lymphoid cell lines using these mAb clearly indicated that most of them were CD4+, CD5+ and CD11a+, and hence derived from CD4+ T cells. These mAb will be useful tools for the study of the cellular immune system in the rabbit.
Animals↗
The role of the interleukin-2 (IL-2)/IL-2 receptor pathway in MRL/lpr lymphadenopathy: the expanded CD4-8- T cell subset completely lacks functional IL-2 receptors.
Autoimmune MRL/MP-lpr/lpr (MRL/lpr) mice spontaneously develop a systemic lupus erythematosus-like disease accompanied by a profound lymphadenopathy that consists of CD4-8-B220+ alpha beta T cells. By the use of cross-linking experiments with radiolabeled interleukin-2 (IL-2), these abnormal T cells have been reported to constitutively express the IL-2 receptor beta chain (IL-2R beta), a signal transducing component of IL-2R, in the absence of the alpha chain (IL-2R alpha). To critically reevaluate the role of the IL-2/IL-2R pathway in the pathogenesis of lymphadenopathy we examined expression of the IL-2R alpha and IL-2R beta in MRL/lpr mice by 125I-IL-2 binding analysis and also by flow cytometric analysis using monoclonal antibodies against each component of the receptor. We found that, contrary to the previous report, the CD4-8-B220+ alpha beta T cells in lymph node (LN) of MRL/lpr mice were negative for both IL-2R alpha and IL-2R beta expression. The lpr liver CD4-8-B220+ alpha beta T cells that had been implicated in the genesis of these abnormal LN T cells were also negative for IL-2R beta expression. Therefore, our results indicate that the IL-2/IL-2R system plays little role, if any, in the expansion of abnormal CD4-8-B220+ alpha beta T cells in MRL/lpr mice.
Animals↗
Characterization of rat LECAM-1 (L-selectin) by the use of monoclonal antibodies and evidence for the presence of soluble LECAM-1 in rat sera.
We have characterized the rat LECAM-1 (L-selectin) by the use of newly generated hamster anti-rat LECAM-1 monoclonal antibodies (mAb) (HRL1, HRL2, HRL3, HRL4), with respect to the biochemistry, cellular distribution and function, and developed an ELISA system to detect the soluble form of rat LECAM-1. In the rat, lymphocyte and neutrophil LECAM-1 have apparent molecular masses of 65 and 62 kDa, respectively, and differential glycosylation may account for the molecular heterogeneity. Readily detectable levels of LECAM-1 are expressed on peripheral blood lymphocytes and neutrophils, but not on thymocytes. Lymphocyte LECAM-1 is rapidly shed from the cell surface upon cell activation with PMA, but not with interleukin (IL)-8. In contrast, neutrophil LECAM-1 showed rapid shedding upon stimulation with phorbol 12-myristate 13-acetate (PMA) or IL-8. Concomitantly there is up-regulated expression of Mac-1 in PMA- and IL-8-stimulated neutrophils. Neutrophil rolling in mesenteric venules was significantly inhibited by administration of function-blocking anti-rat LECAM-1 mAb HRL3, but not by non-blocking HRL4, indicating that LECAM-1 plays a significant role in leukocyte rolling. Given that LECAM-1 is rapidly shed from the cell surface, we attempted to develop an ELISA system for detecting LECAM-1 is soluble form, and measured the levels in experimental autoimmune uveitis. The circulating levels of LECAM-1 increased from day 4, which preceded the appearance of clinical signs of uveitis and remained high until uveitis subsided, suggesting that soluble LECAM-1 is potentially a useful parameter to monitor certain types of inflammatory or immune disorders.
Acute-Phase Reaction↗
Generation of monoclonal antibodies to the rabbit interleukin-2 receptor alpha chain (CD25) and its distribution in HTLV-1-transformed rabbit T cells.
Rabbits can be infected with human retroviruses such as human T-cell leukemia virus-1 (HTLV-1) and human immunodeficiency virus (HIV), and provide useful animal models to study retroviral diseases such as adult T-cell leukemia and HIV. Previously we have succeeded in generating monoclonal antibodies (mAbs) against rabbit CD4, CD5 and CD11a antigens. To make this animal species more amenable to cellular and molecular studies, we have attempted to extend the panel of mAbs against rabbit CD antigens. Here we report on the generation of three neutralizing mAbs against interleukin-2 receptor alpha chain (IL-2R alpha) (CD25), Kei-alpha 1 (IgG2b), Kei-alpha 2 (IgG2a) and Kei-alpha 3 (IgG1). They specifically recognize the rabbit Mr 55,000 IL-2 binding protein, IL-2R alpha, and completely inhibit both high- and low-affinity IL-2 binding to F648b cells that express IL-2R alpha as well as IL-2R beta. The use of mAb Kei-alpha 1 confirmed that the rabbit IL-2R alpha is not only a low-affinity IL-2R on its own but also an essential component of high-affinity IL-2R as found in other animal species, and that rabbit activated T cells including HTLV-1-transformed cell lines express high levels of the IL-2R alpha. Together with mAbs against various rabbit CD antigens that we reported previously, these neutralizing mAbs to IL-2R alpha will be valuable for studies of human retrovirus infections, such as those induced by HTLV-1 or HIV, in rabbits.
Animals↗
[Informed consent and competency in psychiatric practice].
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Humans↗