Biomedical subjects

M Tsujimoto

Publications and source records attributed to M Tsujimoto.

At least 217 records · Page 12Linked to original sources

PubMed1990

Malignant lymphoma of the central nervous system in Japan: histologic and immunohistologic studies.

Ninety-seven Japanese patients with so-called primary non-Hodgkin's lymphoma of the central nervous system (CNS-NHL), unrelated to the acquired immunodeficiency syndrome (AIDS) or organ transplantation, were reviewed. The patients' ages ranged from 1 to 87 years (median: 58 years) with a male to female ratio of 1.77:1. The most frequent past histories were acute appendicitis (appendectomy), head injury, uveitis or iritis, and gastritis or gastric ulcer. These patients presented with symptoms suggesting an expanding intracranial lesion with no signs of extracranial lymphomatous disease. Combined computed tomographic scans, angiography, and findings at surgery or autopsy showed that the cerebrum was the commonest site of involvement, 87% of all cases, with the frontal to temporal region being the most commonly involved. Histologically, the diffuse large-cell type was most frequent and 26% of lymphomas were of high-grade malignancy as defined by the Working Formulation. The reported frequency of high-grade CNS-NHLs in AIDS patients in the United States is much higher (over 60%). Immunohistochemistry on paraffin-embedded sections revealed a B-cell nature of the present series of tumors. In 16% of the cases, large numbers of small lymphoid cells with a positive reaction predominantly for anti-T lymphocyte antibodies surrounded the tumors or aggregated around the capillaries. The tumors which were infiltrated by small lymphoid cells showed more favorable prognosis than those which were not, suggesting a host reaction to tumor growth in these patients.

Acquired Immunodeficiency Syndrome↗

PubMed1990

Mitogenic signalling pathway of tumour necrosis factor involves the rapid tyrosine phosphorylation of 41,000-Mr and 43,000-Mr cytosol proteins.

Tumour necrosis factor (TNF) is a potent mitogen for some fibroblast cell lines. Here we have examined the TNF-mediated changes in protein phosphorylation in Swiss 3T3 and human FS-4 fibroblasts, and compared them with changes observed after the treatment of cells with other mitogens, such as platelet-derived growth factor (PDGF) and bombesin. TNF stimulated the rapid phosphorylation of two 41,000-Mr and two 43,000-Mr cytosol proteins on tyrosine, threonine and/or serine, as did PDGF, epidermal growth factor and fibroblast growth factor; the increased levels of this mitogen-induced protein-tyrosine phosphorylation correlated well with the extent of mitogen-induced DNA synthesis as determined by the percentage of labelled nuclei. In contrast, bombesin, which is an even better mitogen for Swiss 3T3 cells than TNF, stimulated the tyrosine phosphorylation of 41,000-Mr and 43,000-Mr proteins only to a limited extent. On the other hand, bombesin and PDGF stimulated the rapid serine phosphorylation of an 80,000-Mr acidic protein, a major substrate for protein kinase C; increased phosphorylation of the 80,000-Mr protein was not observed at all when cells were stimulated with TNF. These results suggest significant differences among the mitogenic signalling pathways of TNF, PDGF and bombesin as regards the involvement of protein kinases; the mitogenic signalling pathway of TNF involves the activation of tyrosine kinase, but not of protein kinase C, whereas bombesin seems to transduce its mitogenic signal mainly through the activation of protein kinase C, and the activation of both kinases seems to be involved in the mitogenic signalling pathway of PDGF.

Animals↗

PubMed1990

Primary structure of human microsomal dipeptidase deduced from molecular cloning.

Two cDNA clones corresponding to human microsomal dipeptidase (MDP, formerly referred to as dehydropeptidase-I or renal dipeptidase (EC 3.4.13.11] were isolated from human placental and renal cDNA libraries employing rapid amplification of cDNA ends strategy. The complete amino acid sequence deduced from the cDNAs contains 411 residues, beginning with a signal peptide of 16 residues. A highly hydrophobic sequence of 16 amino acids is located at the carboxyl terminus, supporting the previous observation which suggested that mature MDP is anchored to the membrane by covalently attached phosphatidylinositol. MDP has four potential N-glycosylation sites and has no apparent sequence similarity to other metallopeptidases. Expression of immunologically cross-reactive and enzymatically active MDP was attained in COS cells transfected with the cDNA. DNA and RNA blot analyses indicated the existence of a single gene and a substantial amount of 1.8-kilobase mRNA in kidney.

Amino Acid Sequence↗

PubMed1990

Interaction of interleukin-5 with its receptors on murine leukemic BCL1 cells and its implication in biological activity.

Interaction of interleukin (IL)-5 with its receptors on murine leukemic cell line, BCL1 cells was examined. 125I-labeled recombinant murine IL-5(rmIL-5) bound specifically to high-affinity receptors on BCL1 cells. rmIL-5, which was about 2500-fold more active than recombinant human IL-5(rhIL-5) in IgM-inducing activity on BCL1 cells, also showed about 5000-fold higher affinity to receptors. These results suggest that the bioactivity of IL-5 correlates with its receptor-binding activity. When disulfide bond formation was blocked, rmIL-5 dissociated into a monomer and lost its biological activity. This monomeric form of rmIL-5 also lost its ability to bind to cells, suggesting that dimer formation is essential for the biological activity of IL-5.

Animals↗

PubMed1990

4, 6-0-benzylidene-D-glucopyranose (BG) in the treatment of solid malignant tumours, an extended phase I study.

4, 6-0-Benzylidene-D-glucopyranose (BG), a derivative of benzaldehyde (BA), whose anti-tumour action has often been reported, showed responses in 10 out of 24 patients (41.7%). These patients consisted of 11 cases of primary lung cancer, 4 of metastatic lung cancer, 5 of gastric cancer, and one each of cancer of the sigmoid colon, liver, pancreas and prostate. There were two complete responses (one each of ipsilateral lung metastasis from breast cancer and metastatic liver lesions due to gastric cancer). The mean total dose of BG was 392.6 g, given by intravenous infusion of 1.2 g BG in 100 ml saline twice daily. The treatment was discontinued when no response was observed after two months. Careful monitoring showed no toxic action of BG at these large doses. Complete necrotic liquefaction of tumour, without any damage to surrounding tissue, was seen in 2 of 3 cases in which histological examination was feasible. It is apparent that BG, like BA, is not a cytotoxic agent in the ordinary sense, but its mechanism of action is still unknown.

Adult↗

PubMed1990

Structure of recombinant human interleukin 5 produced by Chinese hamster ovary cells.

The complete peptide map of purified recombinant human interleukin 5 (rhIL-5) was determined to verify its primary structure, glycosylation sites, and disulfide bonding structure. Each peptide fragment generated by Achromobacter protease I (API) digestion was purified and characterized by amino acid analysis and amino acid sequence analysis. After digestion with API, we could identify all the peptides which were expected from human IL-5 cDNA sequence. The analyses of sulfhydryl content in rhIL-5 molecule and disulfide-containing peptide obtained from API digestion indicated that active form of rhIL-5 existed as an antiparallel dimer linked by two pairs of Cys-44 and Cys-86. In addition, we concluded that Thr-3 and Asn-28 were glycosylated. The results indicate that primary structure of rhIL-5 is highly homogeneous and observed heterogeneity is due to the difference in the content of carbohydrate.

Amino Acid Sequence↗

PubMed1990

[Temperature-dependent pseudoleukocytopenia and in vitro studies on the underlying mechanism].

Spuriously low electronic white-cell count was obtained on EDTA-anticoagulated blood from a 54-year-old male suffering from liver cell carcinoma. In an attempt to understand better the phenomenon, in vitro studies were performed. The blood smear anticoagulated with EDTA revealed remarkable agglutinations of leukocytes, mainly neutrophils but not lymphocytes. The EDTA-treated blood showed maximal leukocytes-agglutinations at room temperature but no agglutination at 37 degrees C. The agglutinated leukocytes, moreover, were dispersed by incubating the blood at 37 degrees C. Although agglutination occurred in some degree in the blood anticoagulated with Na-heparin or Na3-citrate, it was much less pronounced compared to the EDTA-treated blood. Remarkable leukocytes-agglutinations were induced when EDTA-anticoagulated blood from healthy donor was mixed with serum from the patient at room temperature. These results suggest that the phenomenon of in vitro leukocyte agglutination and consequent pseudoleukocytopenia is due to leukocyte agglutinin in serum from the patient. The mechanisms were discussed comparing with pseudothrombocytopenia caused by platelet agglutinin.

Adolescent↗

PubMed1990

A new technique for one-stage radical eradication of long-standing chronic thoracic empyema.

The surgical treatment of chronic long-standing thoracic empyema remains a challenging subject. A simple technique that consumes less operative time, accompanying less bleeding, and that enables eradication of the disease in one stage was devised by the senior author. The technique requires only three major steps: (1) decortication limited to the parietal sides of the peel's sac, (2) cleansing the empyemic cavity, and (3) drainage. To date, six patients have been treated by this method; complete cure was achieved in all. Neither death nor recurrence of the disease has been noted during the follow-up period averaging 24.5 months. The mean operative time was 3.06 hours, mean bleeding volume was 1262 ml, and the mean hospital stay period was 1.14 months. The methods and results of the technique are discussed.

Aged↗

PubMed1989

Prognostic significance of Ki-67 reactivity in soft tissue sarcomas.

Proliferative activity of soft tissue sarcomas (STS) in 34 cases was estimated by immunohistochemical procedures (avidin-biotin complex [ABC] method) with monoclonal antibody Ki-67 which reacts with a nuclear antigen expressed in all phases of cell cycle except G0. In 20 of 34 cases (59%), varying numbers of Ki-67-positive tumor cells were detected with a range from 5 to 382 per 10 high power fields (HPF) (mean 57.2/10 HPF). Ki-67 index (the number of Ki-67-positive tumor cells/10 HPF) positively correlated with mitotic count (r = 0.428, P less than 0.02), cellularity (r = 0.447, P less than 0.01), and histologic grade (r = 0.473, P less than 0.01). The Ki-67 low index group (less than 50/10 HPF) showed more favorable prognosis than the high index group (more than 50/10 HPF) (P less than 0.005). Three cases with low mitotic count and unfavorable prognosis were proved to be the Ki-67 high index group (142-382/10 HPF). These results indicated that reactivity of tumor cells for Ki-67 is a useful prognostic marker in the patients with STS, and might be used as one of the histologic factors for the grading of STS.

Adolescent↗

PubMed1989

Possible role of prostaglandins as negative regulators in growth stimulation by tumor necrosis factor and epidermal growth factor in human fibroblasts.

Recombinant tumor necrosis factor (TNF), epidermal growth factor (EGF), and transforming growth factor beta (TGF-beta) stimulated growth of confluent human diploid fibroblasts (FS-4 cells) in the presence of fetal calf serum. TGF-beta synergistically enhanced both the TNF- and EGF-stimulated cell growth, whereas synergism between the mitogenic action of EGF and that of TNF was not observed. When indomethacin or acetylsalicylic acid, an inhibitor of prostaglandin production, was added to FS-4 cells, cell growth stimulated by EGF or TNF was increased, suggesting that prostaglandins induced by these mitogens antagonize their growth stimulatory actions. In contrast, neither indomethacin nor acetylsalicylic acid had a significant effect on the TGF-beta-induced growth of FS-4 cells. Mitogenic responses of indomethacin-treated cells to EGF, TNF, and TGF-beta were similarly suppressed by the addition of exogenous prostaglandin D2 (PGD2). Other prostaglandins such as PGE2 and PGF2 produced less inhibition of the cell growth.

Arachidonic Acids↗

PubMed1989

Tumor necrosis factor is cytotoxic to human fibroblasts in the presence of exogenous arachidonic acid.

Recombinant human tumor necrosis factor (TNF) stimulated the growth of confluent human fibroblasts (FS-4) in serum-free culture medium. However, TNF had a cytotoxic effect upon the growth of FS-4 cells in combination with arachidonic acid. When arachidonic acid was added to culture medium in the absence of TNF, however, it had no effect on the cell growth. Arachidonic acid inhibited the TNF-induced cell growth in a dose-dependent manner: it reversed the TNF-stimulated growth to the control level at a concentration of 10 microM and was cytotoxic to TNF-treated FS-4 cells at higher concentrations. This cytotoxicity of TNF was not observed in FS-4 cells treated with palmitic acid. Indomethacin, a cyclooxygenase inhibitor, decreased the cytotoxic effect that TNF exerted in the presence of arachidonic acid. These results suggest that TNF becomes cytotoxic to FS-4 cells when arachidonic acid present in the culture medium is converted to prostaglandins.

Arachidonic Acids↗

PubMed1989

Enhancement of humoral immune responses against viral vaccines by a non-pyrogenic 6-O-acylmuramyldipeptide and synthetic low toxicity analogues of lipid A.

6-O-Acyl derivatives of N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) and synthetic, low toxicity lipid-A analogues were examined for their ability to enhance the potency of current viral vaccines. 6-O-(2-Tetradecylhexadecanoyl)-MDP (B30-MDP) in non-irritative vehicles such as physiological saline, phosphate-buffered saline (PBS), squalene-PBS emulsion, Intralipid or liposomes, significantly stimulated the primary and secondary antibody production of guinea-pigs against influenza split or subunit vaccine and inactivated the hepatitis B virus surface (HBs) antigen. Mice seemed less responsive to the adjuvanticity of B30-MDP than guinea-pigs. Two low toxicity lipid A analogues, acylated beta(1-6)-D-glucosamine disaccharide bisphosphates (which do not have amide-bound or ester-bound 3-acyloxyacyl groups unlike fully toxic Escherichia coli-type lipid A), caused significantly enhanced antibody responses, primary or secondary, when administered to mice by incorporation into liposomes with inactivated HBs antigen.

Acetylmuramyl-Alanyl-Isoglutamine↗

PubMed1989

Purification and characterization of human microsomal dipeptidase.

Human microsomal dipeptidase (MDP, formerly referred to as dehydropeptidase-I or renal dipeptidase) [EC 3.4.13.11] was solubilized from the membrane fraction of kidney by treatment with octyl-beta-D-glucoside and purified by a procedure including ion exchange chromatography and affinity chromatography on cilastatin-immobilized Sepharose. The purified human MDP was found to be homogeneous on sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. The apparent molecular weight (Mr) was estimated by SDS-polyacrylamide gel electrophoresis under non-reducing conditions to be 130 kDa, comprising a homodimer of two subunits. After treatment with endoglycosidase F, human MDP showed a single band with an apparent Mr of 42 kDa on SDS-polyacrylamide gel electrophoresis. Human MDP was found to bind to Con A-Sepharose and the activity was eluted with methyl-alpha-D-mannopyranoside, suggesting that human MDP is a glycoprotein. We also examined the substrate specificity of human MDP and found that human MDP catalyzed the hydrolysis of S(substituent)-L-cysteinyl-glycine adducts such as L-cystinyl-bis(glycine) and S-N-ethylmaleimide-L-cysteinyl-glycine, as well as the conversion of leukotriene D4 to leukotriene E4. These results suggest that MDP might play an important role in the metabolism of glutathione and leukotriene.

Amino Acids↗

PubMed1989

Purification and characterization of recombinant human interleukin 5 expressed in Chinese hamster ovary cells.

Recombinant human interleukin 5 (rhIL-5) expressed in Chinese hamster ovary cells was purified and characterized. Molecular heterogeneity was observed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Two major components of Mr around 40,000 were detected under non-reducing conditions. However, under reducing conditions, the Mr of rhIL-5 was determined to be 22,000 and 20,000. After treatment with endoglycosidase F, a band with an apparent Mr of 18,000 was observed. Treatment of rhIL-5 with 2-mercaptoethanol followed by N-ethylmaleimide resulted in its dissociation into a monomeric form. This alkylated rhIL-5 was biologically less active than intact rhIL-5. These results suggest that rhIL-5 exists as a dimer, and that the heterogeneity of rhIL-5 is mainly due to the difference in the content of carbohydrate. Moreover, the formation of disulfide bond(s) might be important for the biological activity of rhIL-5.

Amino Acid Sequence↗

PubMed1989

Modulation of mitogenic activity of tumor necrosis factor by interferons and dexamethasone.

Effect of interferon (IFN)s on fibroblast growth enhancing activity of tumor necrosis factor (TNF) was examined. IFN-gamma and -beta inhibited TNF-mediated growth stimulation of FS-4 cells. IFNs also inhibited dexamethasone (DEX)-mediated amplification of mitogenic activity of TNF. Significant inhibition was still demonstrable when IFN-gamma was added 2 days after treatment with TNF. On the other hand, no mitogenic activity of TNF was observed when cells were pretreated with IFN-gamma for 6h. These results suggested that interaction between TNF and IFN-gamma might play a role in modulation of some inflammatory processes in vivo.

Cell Line↗

PubMed1989

[Clinical study of taste abnormalities in advanced lung cancer cases].

Taste recognition thresholds for four basic tastes, sweet, salty, and bitter, have been examined in 36 advanced lung cancer patients to identify the presence or absence of taste abnormalities in such patients. Twenty-six untreated lung cancer patients, or 65.3%, demonstrated an abnormal taste threshold for at least one of the 4 taste, a result varying significantly from suitable controls (p less than 0.05). Among the total 36 lung cancer patients, the number of those showing a threshold abnormality was no different between the smoker and non-smoker groups, though abnormalities were higher in the low serum zinc level group than in the normal serum zinc level group (p less than 0.05). We also observed transient threshold elevations after chemotherapy including Cisplatin. Thus, it is thought that taste abnormalities are more prevalent in advanced lung cancer patients.

Adult↗

PubMed1988

Prognostic significance of mast cells in soft tissue sarcoma.

We counted the number of toluidine blue positive mast cells within and around the tumor in 44 patients with soft tissue sarcomas (STS). Irrespective of their histologic types, these cases were broadly divided into the following two groups: (1) low count (less than 20 mast cells/10 high-power fields [HPF]) and (2) high count (greater than or equal to 20 mast cells/10 HPF). The patients with a high mast cell count showed a significantly better 5-year survival rate than those with a low count (85.9% versus 30.5%; P less than 0.01). Five patients with distant metastases at first admission all belonged to the low count group. These results suggest that the number of mast cells within and around the tumor is a useful prognostic factor for STS.

Adolescent↗

PubMed1988

Multivariate analysis for clinical prognostic factors in 163 patients with soft tissue sarcoma.

Clinical and histologic findings in 163 patients with localized soft tissue sarcoma (STS) in the extremities and trunk were reviewed. There were 91 male patients and 72 female patients ranging in age from 2 to 84 years (median, 46 years). The histologic status of the tumors was as follows: low grade, 29 cases; intermediate grade, 52 cases; and high grade, 82 cases. The primary tumors were treated by intralesional excision (two cases), marginal (88), wide local (52), or amputation (21). Subsequent adjuvant therapy was given to 61 patients; 17 had radiotherapy (RT), 27 had chemotherapy (CH), and 17 had combined RT and CH. The overall survival (P less than 0.1) and disease-free survival (P less than 0.001) were better in the group that received multimodal treatment (radical surgery and adjuvant chemotherapy with or without radiotherapy) than in the group treated only by surgery. This suggests the favorable role of adjuvant therapy. The univariate and the Cox multivariate analysis for prognosis revealed that sex, tumor-related symptoms, tumor size, tumor depth, and histologic grade were the significant factors. Among the treatment schemes, adjuvant chemotherapy was the only one that affected survival, especially for the intermediate-grade tumors. Initial surgical treatment (marginal versus wide local excision) significantly contributed to the local control of the primary tumors.

Actuarial Analysis↗