Biomedical subjects

M Kojima

Publications and source records attributed to M Kojima.

At least 1,135 records · Page 63Linked to original sources

PubMedDate not supplied

Activities of the MBL-associated serine proteases (MASPs) and their regulation by natural inhibitors.

There has been rapid progress in determining the mechanism by which complement is activated by the complex formed between Mannose-Binding Lectin and its associated proteases (MASPs). MBL and the MASPs are of low abundance, but are similar to the more abundant C1q-C1r2s2 complex (C1), which has been extensively investigated. In this review we summarise recent findings on MBL-MASPs' structure. enzymic activity and regulation, and compare MBL-MASPs with C1.

Animals↗

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Functional interleukin-4 receptor and interleukin-2 receptor common gamma chain in human gastric carcinoma: a possible mechanism for cytokine-based therapy.

Interleukin (IL)-2 and IL-4 play a critical role in the regulation of the immune response. Yet both of the receptors for these cytokines have been found on nonhematopoietic cells, including human gastric carcinoma cell lines and tissue specimens. IL-4 causes G1 phase cell cycle arrest of gastric carcinoma; the effect directly correlates with the expression of IL-4 receptor (IL-4R) and is seen within 48 hours after treatment. Cells lacking IL-4R are unaffected by IL-4. We examined signal transduction pathways employed by IL-4 that may account for cell cycle arrest of an established human gastric carcinoma cell line, CRL 1739. Western blot analysis was performed on CRL 1739 cultured in the presence of IL-4 (500 U/ml). Cells were lysed, protein extracted, and electroblotted; blots were then probed with murine mono-clonal antibodies to specific intracellular proteins. Western blotting of CRL 1739 with antiphosphotyrosine antibody (4G10) demonstrated multiple (140 kDa and 65 kDa) phosphoproteins seen only in IL-4-treated CRL 1739. Immunoprecipitation and blotting of CRL 1739 with specific secondary antibodies demonstrated that the 140 kDa phosphoprotein was IL-4R", the 65kDa phosphoprotein was IL-2Rgc, the 130 kDa phosphoprotein was Janus kinase (JAK1), and the 116 kDa phosphoprotein was JAK3. Reverse transcription-polymerase chain reaction with specific primers demonstrated that multiple human gastric tumor specimens expressed IL-4R" and IL-2Rgc but did not express the leukocyte marker CD45. These results suggest that human gastric carcinomas may express functional cytokine receptors, including the IL-2Rgc commonly found in association with the lymphocyte IL-2R. These receptors may represent novel targets for directing cytokine-based therapy.

Biopsy↗

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I-J as an idiotype of the recognition component of antigen-specific suppressor T-cell factor.

The I-J determinant of membrane glycoprotein is known to be expressed exclusively on suppressor T cells (TS), which have a crucial role in the regulation of immune responses. I-J also comprises part of the soluble factor (TSF) with suppressor activity which is secreted from TS. Gene-mapping experiments have indicated that the I-J gene lies between the I-A and I-E subregions of the mouse major histocompatibility complex (MHC) and is defined by the H-2 congeneic pair, that is, B10.A(3R) and B10.A(5R). In fact, antibodies raised in the reciprocal combinations of B10.A(3R) and B10.A(5R) define the I-Jb and I-Jk alleles, and are able to detect the I-J determinants on TS and TSF. Biochemical and functional analyses, using I-J-positive TS clones and hybridomas, have demonstrated that monoclonal anti-I-J antibodies precipitate I-Jk or I-Jb with a relative molecular mass of 25,000-28,000 (25-28K) and that the I-J+ molecule mediates the restriction specificity of TSF in association with an antigen-binding protein (45K). However, molecular genetic studies on the I-J gene reveal no genetic difference between B10.A(3R) and B10.A(5R) and also that there is no room to accommodate a gene encoding I-J in the expected I region. These discrepancies between the molecular genetic and serological/functional data require explanation. Here we demonstrate that TS and TSF expressing I-J of the host type were produced by fully allogeneic bone marrow cells of donor origin in chimaeric mice, when the chimaeras received the host antigen-presenting cells (APC) at the time of immunization. The results show that APC are necessary for the activation and clonal expansion of TS and also support the notion that I-J is an idiotypic determinant of the recognition component of TS and TSF.

Animals↗

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Primary structure of the receptor for calcium channel blockers from skeletal muscle.

The complete amino-acid sequence of the receptor for dihydropyridine calcium channel blockers from rabbit skeletal muscle is predicted by cloning and sequence analysis of DNA complementary to its messenger RNA. Structural and sequence similarities to the voltage-dependent sodium channel suggest that in the transverse tubule membrane of skeletal muscle the dihydropyridine receptor may act both as voltage sensor in excitation-contraction coupling and as a calcium channel.

Amino Acid Sequence↗

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Gender differences in social and interpersonal features and personality disorders among Japanese patients with obsessive-compulsive disorder.

This study sought to elucidate the differential effect of gender on clinical features in 40 males and 54 females who met both DSM-III-R and DSM-IV criteria for obsessive-compulsive disorder (OCD). Males had a lower rate of marriage, and a higher rate of major impairment in social or occupational functioning, whereas females were significantly more likely to involve others in their OCD symptoms, such as reassurance-seeking. Although no significant differences were detected in the distribution of OCD symptoms, cluster A personality disorders (PDs), especially schizotypal PD, were more frequently diagnosed in males, and borderline and dependent PDs tended to be more prevalent in females. Thus, gender differences in OCD subjects were prominently observed in social or interpersonal features, which might be consistent with the differential PD pathology between males and females.

Adult↗

PubMedDate not supplied

An economical synthesis of famciclovir.

An economical synthesis of famciclovir from N-2-acetyl-7-benzylguanine by a novel regioselective alkylation with the diester cyclopropane compound was developed.

2-Aminopurine↗

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Effects of prenylamine on transmembrane action potentials as related to the change in external potassium concentrations in guinea pig papillary muscle.

We studied the effects of 4.8 muM prenylamine on transmembrane potentials in isolated guinea pig papillary muscles using a conventional microelectrode technique and compared them with those of 36.9 microM lidocaine. Prenylamine reduced Vmax at 1 Hz increasingly as the external potassium, [K]o, was increased from 2.7 to 10 mM. The reduction was also increased as the driving rate was increased from 0.25 to 5 Hz. The rate-dependent depression was less in 2.7 and 8.1 mM with 7.2 mM [Ca]o and more in 5.4 and 8.1 mM [K]o with 1.8 mM [Ca]o. Prenylamine produced a marked delay in the recovery of Vmax in premature responses inserted between constant driving stimuli at 0.25 Hz. The delay was also less in the former two, and more in the latter two media. Thus the effects of prenylamine on Vmax were more rate dependent and less [K]o-dependent than those of 36.9 microM lidocaine. At the diastolic interval of 100 ms, prenylamine depressed the overshoot, action potential duration at 0 mV level (APDo) and Vmax in premature responses more markedly than did 36.9 microM lidocaine, the differences of the effects being more significant for the first two. The results are interpreted as representing the calcium-antagonistic property of prenylamine of which lidocaine appears to be devoid.

Action Potentials↗

PubMedDate not supplied

Hemodynamic and electrophysiological effects of a novel positive inotropic drug, OPC-8212, in normal and "failing" guinea pig heart preparations.

OPC-8212, 3,4-dihydro-6-[4-(3,4-dimethoxy-benzoyl)-1-piperazinyl]-2 (1H)-quinolinone, significantly decreased heart rate and increased contractility (+ dP/dt) and coronary flow in isolated, perfused guinea pig Langendorff and work-performing heart preparations. The effect on contractility, but not on coronary flow, was significantly greater when the negative chronotropic effect was prevented by pacing. In guinea pig hearts made incompetent by aortic stenosis, OPC-8212 produced a significant increase in contractility and coronary flow and greater negative chronotropic effects than in control hearts. OPC-8212 improved the work performance of normal and "failing" isolated work-performing guinea pig hearts during pressure load and during volume load. In electrophysiological studies, OPC-8212 enhance Vmax, amplitude, and duration of fast action potentials (APs) in guinea pig papillary muscles. Tetraethylammonium (TEA)-induced slow APs were also potentiated with respect to Vmax, amplitude, and duration. OPC-8212 in the absence of TEA also lowered the voltage threshold for inducing the slow APs. Positive inotropic effects, but not the slow APs, of guinea pig papillary muscles were greatly enhanced by OPC-8212 at higher frequencies of stimulation (2-3 Hz), indicating an important mechanism of action that may be at least in part independent of Isi.

Action Potentials↗

PubMedDate not supplied

Phenotypic analysis of peripheral T cell lymphoma among the Japanese.

From 1980 to 1990, 174 peripheral T cell lymphomas were studied morphologically and immunophenotypically with a panel of monoclonal antibodies which were reactive with T cell differentiation antigens in cryostat sections and/or cell suspensions. Histologically, 57% of the lymphomas were categorized into low-grade tumors according to the updated Kiel classification, while 41% were high-grade tumors. By immunologic studies, 50% of the lymphomas were of helper/inducer (CD4) phenotype, 6% were of cytotoxic/suppressor (CD8) phenotype, 3% expressed both CD4 and CD8, 3% lacked both CD4 and CD8, and 36% were phenotypically undetermined because of an admixture of a fairly even number of CD4 and CD8-positive cells. The phenotypically undetermined cases were more frequently noted in the low-grade groups than in the high-grade group, and the latter often showed a loss of pan-T antigens, although there was no definite correlation between the histologic category and the immunophenotype. CD25, which is strongly manifested in anti-HTLV-1 antibody-positive cases, was negative or only weakly expressed in anti-HTLV-1 antibody-negative cases. Anaplastic large cell lymphomas (LC-Ana) strongly expressed CD30, which was also detectable in only large blast-like cells in the low-grade tumors. Seventy-one per cent of the lymphomas expressed Ia antigens. In this series, the clinical data were available on 154 patients. For individual markers, the expression of CD30 and HLA-DR were associated with a longer actuarial survival (P < 0.01 and P < 0.05 by the generalized Wilcoxon test). The absence of CD25 or the presence of CD3 on tumor cells correlated with a relatively favorable prognosis, but not significantly. The detection of CD4 and CD8 had relatively little prognostic value. In the cases excluding LC-Ana, a significant difference was also recognized between the groups with and without CD25, CD30 and HLA-DR (P < 0.05 by the generalized Wilcoxon test). These results suggest that the immunophenotypic analysis of peripheral T cell lymphoma provided its use as an adjunct to a histopathologic diagnosis and was related to prognostic prediction.

Biomarkers↗

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Abscess-forming granulomatous lymphadenitis: histological typing of suppurative granulomas and clinicopathological findings with special reference to cat scratch disease.

In order to clarify the histological and immunohistochemical characteristics of suppurative granuloma in abscess-forming granulomatous lymphadenitis (AGL), and the relation between AGL and cat scratch disease (CSD), 36 cases of AGL were studied. The combined results showed that there were two types of suppurative granulomas. The suppurative granulomas histologically revealed small lymphocytes of predominantly T cell phenotype distributed among the epithelioid histiocytes bordering central necrotic areas in the suppurative granulomas. These suppurative granulomas could be further subdivided into two groups, mainly those with and without the intermingling of large transformed cells of B-cell phenotypes: Type B granuloma with large transformed B cells and Type A without large transformed B cells. Both types of granulomas were observed in a varying degree in most cases. According to the predominant type of granulomas, 36 patients with AGL were further classified into two groups: Group I of Type A dominance and Group II of Type B dominance. Warthin-Starry (WS) silver stain positive bacteria, which are said to be a causative agent of CSD, were present in about 50% of both groups. No Brown-Hopps' Gram-positive bacteria, fungus, toxoplasma, Chlamydia or Bacillus Calmette-Guérin antigen were found in any case. Clinically, there was no significant difference between these two groups. On the other hand, the detection of WS-positive bacteria seemed to have some relationship with the duration of disease and the history of exposure to cats, and 70% of AGL cases occurred in autumn without a single concurrent epidemic.

Adolescent↗

PubMedDate not supplied

Clinicopathologic study of primary mediastinal non-lymphoblastic non-Hodgkin's lymphomas among the Japanese.

We studied the morphologic, immunologic and clinical features of 14 cases of primary non-lymphoblastic non-Hodgkin's lymphomas of the mediastinum. The patients ranged in age from 3 to 76 years, with a median age of 28 years. According to the Ann Arbor classification, 71% of our cases were in an early stage. Three cases were in Stage I, eight in Stage II, one in Stage III and two in Stage IV (one with multiple hepatic lesions and another with bone marrow involvement). The patients were heterogeneous in terms of the disease and were therefore histologically classified into three categories: diffuse large B cell lymphoma with sclerosis (DLS; n = 8); large cell anaplastic lymphoma (LC-Ana; n = 5); and low grade B cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma; n = 1). DLS was the most common group and was characterized as CD5-, CD10-, CD19+, CD20+, CD21- and CD22+. Imprint smears showed azurophilic granules in the cytoplasm of the tumor cells of three of four DLS cases. All of the six cases examined were negative when tested for Epstein-Barr virus (EBV) sequences after hybridization with the EBV internal repeat probe. DLS and MALT lymphoma cases were of a B-lineage lymphoma of the thymus, while most of the LC-Ana cases were of a T-lineage lymphoma. Patients with non-lymphoblastic non-Hodgkin's lymphomas had a relatively favorable prognosis compared with lymphoblastic lymphoma (P < 0.01 by the generalized Wilcoxon test). There was no significant difference in the survival between non-lymphoblastic non-Hodgkin's lymphoma and Hodgkin's disease (P > 0.05 by the generalized Wilcoxon test).

Adolescent↗

PubMedDate not supplied

Reactive hyperplasia with giant follicles in lymph node lesions from systemic lupus erythematosus patients. Report of three cases.

Lymph node enlargement is common in active systemic lupus erythematosus (SLE), a disease that is characterized by well-defined clinical criteria. Histologically, although lymphadenopathy associated with SLE exhibits marked histological diversity and occasionally shows atypical lymphoproliferative disorders, there has not been any description of the histopathological features of reactive lymph node hyperplasia with giant follicles (RHGF). We here report three such cases. The subjects were a 23-year-old Japanese female, a 44-year-old Japanese female and a 49-year-old Japanese male. All three patients initially presented with systemic lymphadenopathy. They also had systemic symptoms and abnormal laboratory findings indicating active disease, although two patients did not fulfill the diagnostic criteria for SLE at lymph node biopsy. Histologically, three lesions were characterized by numerous enlarged, coalescing lymphoid follicles with distortion rather than effacement of the lymph node architecture. By in situ hybridization, Epstein-Barr virus (EBV) genomes were demonstrated in two cases. The present three cases indicate that lymphadenopathy associated with SLE representing RFGH should be differentiated from the early stage of HIV-related lymphadenopathy as well as follicular lymphoma, particularly the floral variant. The authors would like to stress that the RHGF which is described in the present study should be listed in the pathohistology of SLE lymphadenopathy.

Adult↗

PubMedDate not supplied

Contractile responses in human umbilical arteries to hyper- and hypotonic solutions.

The effects of hyper- and hypotonic solutions on vascular smooth muscle were studied using helical strips from human umbilical arteries. Hypertonic solutions evoked a biphasic contraction that consisted of early and late contractions. Verapamil or Ca(2+)-free conditions inhibited early contraction induced by tonicity of 340-539 mosm/kg. Under these conditions, late contraction induced by 340-407 mosm/kg was inhibited, whereas contraction induced by 539 mosm/kg was not. Hypotonic solutions evoked a monophasic contraction. Verapamil or Ca(2+)-free conditions inhibited contraction induced by tonicity of 249-266 mosm/kg but not by tonicity of 213 mosm/kg. Hyper- or hypotonicity-induced contractions were not affected by the presence or absence of endothelium. These results suggest that a small increase or decrease in tonicity within the pathophysiological range of osmotic pressure (260-340 mosm/kg) evokes contraction in human umbilical arteries by stimulating calcium influx through voltage-sensitive Ca2+ channels.

Animals↗

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Early changes of experimentally induced cerebral aneurysms in rats: scanning electron microscopic study.

To obtain information about the early changes of experimentally induced cerebral aneurysms in rats, the luminal surface of branching areas of their cerebral arteries was examined with a scanning electron microscope. At the branching sites of major cerebral arteries in the control animals, the intima just distal to the apex markedly protruded into the lumen forming a linear bank-like intimal pad. Along and distal to this pad, there was a shallow long groove (juxta-apical groove). Such grooves were much deeper and wider in experimental animals than those in the control rats. By studying various stages of early aneurysmal changes, cerebral aneurysms were proven to develop from such grooves. In deep juxta-apical grooves and small aneurysms, round regenerated endothelial cells with a large number of microvilli were diffusely present. Degenerated cells with balloons and craters were observed intermingled with such regenerated cells. Interendothelial gaps were also seen. The present study showed the complex structure of the apex of arterial bifurcation in rats, including bank-like intimal pads. Such complex structures of the branching sites were considered to be responsible for the initiation of cerebral aneurysms due to endothelial injury possibly caused by turbulent flow there.

Animals↗

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The micronucleus assay with mouse peripheral blood reticulocytes using acridine orange-coated slides with triethylenemelamine.

A micronucleus assay using mouse peripheral blood and supravital staining with acridine orange (AO) was validated by two laboratories on triethylenemelamine-treated mice. Dose- and time-dependent increases in micronucleated peripheral reticulocytes were observed. This new method can be used as an alternative to the conventional bone marrow micronucleus assay.

Acridine Orange↗

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Nursing education in Japan and its future trends.

As its title indicates, this article describes the development of Japanese nursing education over several decades, the stage it has reached today, the aspirations of the nursing profession for the future upgrading of nursing education, and the trends which are evolving in this direction.

Curriculum↗

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Permeation of lipophilic drugs through synthetic elastomers.

Permeability studies were carried out with three lipophilic drugs, namely, phenytoin and primidone (both widely used in the treatment of epilepsies and convulsive disorders), and dapsone (a sulfone antimicrobial agent used in the treatment of leprosy and to a lesser extent in dermatitis herpetiformis) through silica-filled poly(dimethyl siloxane) (Silastic) membranes, and anisotropic membranes of poly(ether-urethane)/poly(dimethyl siloxane) block copolymer (Avcothane, Cardiothane). These polymers are used in medical implants and in various cardiovascular devices. While both polymers were permeable to the drugs, the transport properties differed significantly. In the case of the poly(dimethyl siloxane) there was an initial large burst effect, followed by an exponential decrease in the rate of drugs released through the polymer films, although with dapsone the release rate became essentially constant between 100-180 h at 37 degrees C. In the case of the anisotropic films of the poly(ether-urethane)/poly(dimethyl siloxane) block copolymer, the permeabilities were much higher. Significantly, phenytoin exhibited essentially constant rate (zero-order) kinetics between 25-150 h, showing only a moderate burst effect that is probably not significant therapeutically. Importantly, dapsone showed neither a burst effect nor any significant time lag, and the release followed constant rate (zero-order) kinetics between 12-80 h, followed by only a moderate decrease in drug concentration up to 140 h (the experimental end-point). The diffusion coefficients calculated from initial desorption data at 37 degrees C for the poly(ether-urethane)/poly(dimethyl siloxane) block copolymer are as follows: phenytoin = 8.6 X 10(-9) cm2/s, primidone = 2.8 X 10(-9) cm2/s, and dapsone = 2.4 X 10(-8) cm2/s.(ABSTRACT TRUNCATED AT 250 WORDS)

Dapsone↗

PubMedDate not supplied

Daily intakes of tributyltin and triphenyltin compounds from meals.

Daily intakes of tributyltin (TBT) and triphenyltin (TPT) compounds from meals in Shiga Prefecture, Japan, were investigated by 2 methods. Daily intakes of TBT and TPT by the duplicate portion method were, respectively, 4.7 and 0.7 microgram in 1991 and 2.2 and 0.7 microgram in 1992. Those by the market basket method were, respectively, 6.9 and 5.4 micrograms in 1991 and 6.7 and 1.3 micrograms in 1992. Daily intakes of TBT and TPT by the market basket method were higher than those by the duplicate portion method. These values were considerably lower than acceptable daily intakes of 80 micrograms/50 kg body weight specified by the Welfare Ministry of Japan for bis(tri-n-butyltin)oxide and of 25 micrograms/50 kg body weight specified by the Food and Agriculture Organization/World Health Organization for TPT.

Adult↗