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Biomedical subjects

M Matsuda

Publications and source records attributed to M Matsuda.

At least 667 records · Page 37Linked to original sources

[Central nervous system metastasis from lingual carcinoma: report of a case].

A rare case of lingual carcinoma which metastasized to the brain is reported. A 66-year-old man was referred to our department on April 23, 1991, with complaints of memory disturbance and mild left motor weakness of one month's duration. The patient had been discharged from the Department of Otolaryngology of our hospital 9 months before, after undergoing radical neck dissection and chemotherapy (THP, CDDP, PEP) for his lingual cancer with metastases to the cervical lymph nodes and the lung. On admission to our department, the patient complained of mild frontalgia. Neurological examination showed memory disturbance, change of character, mild left hemiparesis and urinary incontinence. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed a well circumscribed mass in the right frontal lobe associated with midline shift toward the left. Systemic Gallium-67 scintigraphy demonstrated an abnormal uptake in the right frontal region, but no abnormal uptake was seen in the neck and the lung. The most likely diagnosis was thought to be metastasis of lingual cancer. The patient underwent tumor removal 10 days after admission. A histological examination of the tumor specimen revealed metastatic anaplastic cell carcinoma, indicating a metastasis from lingual carcinoma. After postoperative radiotherapy (total 60 Gy), the patient was discharged without neurological deficit. Central nervous system metastasis from lingual carcinoma is quite rare. To the best of our knowledge, only two such cases have been reported. We report another rare case of solitary brain metastasis from lingual carcinoma and review the pertinent medical literature.

Aged↗

[Clinical effect and characteristics of low dose leucovorin and high dose 5-FU therapy in patients with recurrent gastric cancer--a new method of biochemical modulation].

The biochemical modulation of 5-fluorouracil (5-FU) and leucovorin (LV) has resulted in a remarkable increase of the response rate in patients with colorectal cancer. Recently, in the treatment of gastric cancer this biochemical modulation has been introduced into clinical practice and has also achieved good antitumor activity. A review of the literature indicates that 5-FU/LV therapy for gastric cancer is effective only when LV is administered at high doses (200 mg-500 mg/m2), and the efficacy of low dose LV (20 mg/m2) administration with the combination of high dose 5-FU is still unknown. Thirty-five patients with measurable recurrent gastric cancer received low dose LV and high dose 5-FU for 4 days. The schedule was as follows: iv injection of low dose leucovorin (20 mg/m2) and from one hour later 2-hour infusion of high dose 5-FU (700 mg/m2). This new treatment for recurrent gastric cancer achieved a response rate of 40.0%, and 80.0% of the patients with pronounced palliative effects measured as recurrence-related symptoms. It is very rare for 7 out of 8 patients (87.5%) to be relieved of obstructive jaundice, and we now prefer this therapy to percutaneous transhepatic biliary drainage in patients with jaundice. The toxicity of this biochemical modulation is leukopenia, stomatitis and diarrhea, and the number of patients with toxicity over grade 3 was 5 (14.3%). There was no treatment-related death.

Adult↗

Decrease of plasma large, light LDL (LDL1), HDL2 and HDL3 levels with concomitant increase of cholesteryl ester transfer protein (CETP) activity by probucol in type II hyperlipoproteinemia.

The effects of 12 week probucol treatment on plasma lipoprotein subfraction levels and on lecithin: cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) activities in type II hyperlipoproteinemia were investigated. Plasma VLDL-TG, VLDL-apoB, VLDL-apoCII and VLDL-apoCIII concentrations were not changed by probucol, but VLDL-TC and VLDL-PL levels were slightly reduced. Probucol slightly reduced plasma IDL-TC, but not IDL-TG, IDL-PL and IDL-apoB levels. Plasma large, light LDL (LDL1)-TC, LDL1-PL, LDL1-apoB levels were decreased significantly by 28.5 +/- 20.1% (p < 0.001), 18.1 +/- 18.8% (p < 0.01) and 23.3 +/- 19.1% (p < 0.001) by probucol treatment while LDL1-TG concentration was unchanged. Absolute amounts of plasma small, heavy LDL(LDL2)-TC, LDL2-TG, LDL2-PL and LDL2-apoB levels remained unchanged but percent increases of LDL2-TC and LDL2-apoB were statistically significant (p < 0.05). 2-16% gradient polyacrylamide gel electrophoresis demonstrated the diminution of LDL of large size by probucol treatment. Probucol markedly reduced plasma high density lipoprotein levels. The reductions of HDL2-TC, HDL2-TG, HDL2-PL and HDL2-apoAI concentrations were 36.2 +/- 25.4% (p < 0.001), 25.8 +/- 36.9% (p < 0.01), 34.4 +/- 23.8% (p < 0.001) and 35.6 +/- 28.4% (p < 0.001). Probucol significantly decreased plasma HDL3-TC, HDL3-PL and HDL3-apoAI amounts by 17.4 +/- 22.9% (p < 0.01), 18.3 +/- 20.8% (p < 0.01) and 19.8 +/- 27.9% (p < 0.01) without change of HDL3-TG level. The decrease of HDL2 level was more marked than that of HDL3 level. Probucol did not change LCAT activities. Probucol significantly stimulated CETP activities from 126.6 +/- 50.6 units to 172.8 +/- 40.2 units by 12 week treatment (p < 0.001). We concluded that probucol decreased plasma LDL1, HDL2 and HDL3 amounts and made them triglyceride-rich with the concomitant increase of CETP activities.

Carrier Proteins↗

[A new technique for evaluating the respiratory tract--digital subtraction bronchography (DSBG)].

Bronchography is essential for evaluation of morphological changes in the bronchial tree. However, conventional bronchography using Propyliodone (Dionosil) is extremely invasive, especially to those with pulmonary infections. In the present study, we developed a new less invasive method of bronchography with the aid of digital subtraction technique (DSBG), and evaluated its clinical benefits. Bronchography was performed by injecting contrast medium (Iopamidol: Iopamiron 300) via the lumen of the bronchoscope (Olympus Type 20), and image processing of the respiratory tract was performed using digital subtraction technique. From 1991 to 1992, DSBG was performed in 15 cases (8 bronchiectasis, 1 diffuse panbronchiolitis, 1 lung cancer, 1 pulmonary emphysema, and 4 others). DSBG clearly demonstrated the morphological changes of large and segmental bronchial lesions in cases of bronchiectasis and lung cancer, as well as conventional bronchography using Dionosil. In addition, it was possible to image the morphological changes of bronchiolar lesions in diffuse panbronchiolitis and pulmonary emphysema to the same detail as obtained using classical selective alveolo-bronchography (SAB). Since DSBG can provide enhanced images the bronchial tree without being affected by cardiac and respiratory movements, we could obtain detailed information on bronchial and/or bronchiolar lesions. With respect to side effects, Iopamiron was quickly drained and/or absorbed within 2 hours after injection. Pulmonary infection and bronchial bleeding, which are well known primary complications of classical bronchography using Dionosil, were not observed. We conclude that 1) DSBG is useful new technique for examining morphological changes of the respiratory tract, and 2) DSBG is less invasive than conventional bronchography.

Adult↗

An abnormal protein C (protein C Yonago) with an amino acid substitution of Gly for Arg-15 caused by a single base mutation of C to G in codon 57 (CGG-->GGG). Deteriorated calcium-dependent conformation of the gamma-carboxyglutamic acid domain relevant to a thrombotic tendency.

Protein C Yonago is a dysfunctional protein C characterized by defective anticoagulant activity determined by a coagulation assay and normal amidolytic activity measured on a synthetic substrate S-2366 (Iijima et al., Thromb Res 1991;63:249-257). We have identified a single point mutation of C to G in codon 57 (CGG-->GGG) of the gene for protein C Yonago by genetic analysis utilizing the polymerase chain reaction. The mutation should have resulted in an amino acid substitution of Gly for Arg at position 15 of the light chain of mature protein C. No mutations were found in nucleotides spanning the putative gamma-carboxylase recognition site or gamma-carboxyglutamic acid residues of protein C. Protein C Yonago was non-reactive to monoclonal antibodies JTC-1 and -3 that solely recognized the calcium-dependent conformation of the gamma-carboxyglutamic acid domain. This indicated that the mutation had critically perturbed the highly conserved structure of the gamma-carboxyglutamic acid domain. Thus, the calcium-dependent conformation required for the phospholipids binding to exert the physiological functions of protein C may not have been elicited normally in this abnormal protein C, resulting in defective generation of anticoagulant activities in plasma. Consequently, no anticoagulant activities may have been generated in vivo.

1-Carboxyglutamic Acid↗

Reversible interactions between plasminogen activators and plasminogen activator inhibitor-1.

We have shown that the urokinase (UK) kringle domain contains a high-affinity plasminogen activator inhibitor-1 (PAI-1) binding site, responsible for the 10-fold faster complex formation between UK and PAI-1 than between PAI-1 and low-molecular-weight urokinase (LMWUK). Complex formation between UK and PAI-1, but not between LMWUK and PAI-1, was suppressed 10-fold in the presence of peptide U-107 derived from the UK kringle domain. Peptide U-373 derived from the UK catalytic domain slowed complex formation between UK and PAI-1 and also LMWUK and PAI-1. Inactivation of tissue-type plasminogen activator (tPA) by PAI-1 was slowed 10-fold in the presence of peptides derived from the tPA finger and kringle-2 domains. DFP-inactivated (DIP) UK and both forms of DIP-tPA inhibited PAI-1 binding to U-107 and to U-373 whereas single-chain urokinase-type PA (scuPA) was unable to compete with either peptide for PAI-1 binding. These data suggest that the reversible PAI-1 binding site in the UK A-chain plays a role in the rapid association with PAI-1 as important as those that reside in the tPA A-chain and that reversible PAI-1 binding sites are expressed on the surface of UK upon conversion from scuPA, in contrast to tPA.

Amino Acid Sequence↗

Studies on pyridonecarboxylic acids. 1. Synthesis and antibacterial evaluation of 7-substituted-6-halo-4-oxo-4H-[1,3]thiazeto[3,2-a]quinoline-3- carboxylic acids.

A series of [1,3]thiazeto[3,2-a]quinoline-3-carboxylic acids and their esters were prepared and evaluated for antibacterial activity. The derivatives with a hydrogen or methyl group at C-1, fluorine at C-6, and piperazinyl or 4-methyl-1-piperazinyl group at C-7 showed superior in vitro antibacterial activity, and the derivatives with 4-methyl-1-piperazinyl group at C-7 had potent in vivo activity. Compound 29a (NM394) showed excellent in vitro antibacterial activity and low toxicity but poor absorption from the gastrointestinal tract. Compound 29ee (NM441), an N-[(5-methyl-2-oxo-1,3-dioxol-4-yl)methyl] derivative of 29a, was found to possess a favorable pharmacokinetic profile and oral activity superior to that of ciprofloxacin in experimental animals.

Administration, Oral↗

Heterozygous abnormal fibrinogen Osaka III with the replacement of gamma arginine-275 by histidine has an apparently higher molecular weight gamma-chain variant.

Congenitally abnormal fibrinogen Osaka III with the replacement of gamma Arg-275 by His was found in a 38-year-old female with no bleeding or thrombotic tendency. Release of fibrinopeptide(s) by thrombin or reptilase was normal, but her thrombin or reptilase time in the absence of calcium was markedly prolonged and the polymerization of preformed fibrin monomer which was prepared by the treatment of fibrinogen with thrombin or reptilase was also markedly defective. Propositus' fibrinogen had normal crosslinking abilities of alpha- and gamma-chains. Analysis of fibrinogen chains on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) in the system of Laemmli only revealed the presence of abnormal gamma-chain with an apparently higher molecular weight, the presence of which was more clearly detected with SDS-PAGE of fibrin monomer obtained by thrombin treatment. Purified fragment D1 of fibrinogen Osaka III also seemed to contain an apparently higher molecular weight fragment D1 gamma remnant on Laemmli gels, which was digested faster than the normal control by plasmin in the presence of [ethylenebis(oxyethylenenitrilo)]tetraacetic acid (EGTA).

Adult↗

Delta-thalassemia caused by disruption of the site for an erythroid-specific transcription factor, GATA-1, in the delta-globin gene promoter.

Delta-thalassemia is a complex group of inherited disorders of globin genes characterized by impaired synthesis of the delta-globin chain. The T-C substitution was detected at position -77 of the delta-globin gene isolated from three independent Japanese individuals who were homozygotes for delta-thalassemia. To elucidate the significance of the mutation in delta-globin gene expression, we investigated the genotype of three delta-thalassemia homozygotes and 58 normal individuals using dot blot hybridization of the polymerase chain reaction (PCR)-amplified DNA. The mutation was observed in six alleles of three homozygotes, while no mutation was detected in 116 alleles of normal individuals, thereby indicating the close association of this mutation with the thalassemia phenotype. Since the mutation (TTATCT-TCATCT) is located within the inverted binding motif of GATA-1 (T or A-G-A-T-A-G or A), an erythroid cell-specific transcription factor, we did gel retardation assays using nuclear extracts from the erythroid cells. We found that GATA-1 binds the oligonucleotide spanning positions -61 to -90, but does not bind to the oligonucleotide with the mutation at position -77. Competition gel retardation assays showed that GATA-1 binding can be competed out by the fragment with the GATA-1 motif, but not with the mutant oligonucleotide. Analysis of the transient expression of the CAT gene linked to the delta-globin gene promoter region demonstrated that the construct with the mutant promoter region was expressed about 20-fold less compared with the normal one. Thus, the mutation at position -77 impairs delta-globin gene expression by abolishing GATA-1 binding to the AGATAA sequence of the promoter region of the delta-globin gene. This provides a good example of involvement of tissue-specific transacting factors in the molecular pathogenesis of hereditary diseases.

Base Sequence↗

Calmodulin is involved in catecholamine secretion from digitonin-permeabilized bovine adrenal medullary chromaffin cells.

The role of calmodulin in exocytotic secretion was studied using digitonin-permeabilized bovine adrenal medullary chromaffin cells. Addition of calmodulin to the permeabilized cells increased Ca(2+)-dependent norepinephrine release in a dose-dependent manner. Unlike calmodulin, addition of caldesmon, actin or bovine serum albumin did not increase the release. Calmodulin increased the release at Ca2+ concentrations of more than 10(-6) M and its effect increased with increase in Mg2+ concentration. Th release of norepinephrine enhanced by calmodulin was inhibited by tetanus toxin, which specifically inhibits exocytotic secretion. These results indicate directly that calmodulin plays an important role in exocytotic secretion from chromaffin cells.

Actins↗

Nonrandom distribution of gp120 N-linked glycosylation sites important for infectivity of human immunodeficiency virus type 1.

More than 20 consensus N-linked glycosylation sites occur in the gp120 coding sequence of most isolates of human immunodeficiency virus type 1. Based on the N-linked glycosylation pattern of a well-characterized recombinant gp120, it is likely that N-linked sugars are present at most, if not all, of the consensus glycosylation sites of the heavily glycosylated gp120. In this study, we evaluated the relative importance of each of the 24 N-linked glycosylation sites of gp120 in the molecular clone HXB2 to viral infectivity. The ability of HXB2-derived mutants, each having 1 of the 24 N-linked glycosylation sites mutated by site-directed mutagenesis, to infect CD4-positive SupT1 cells was compared with that of the wild-type virus. We found that most of the individual consensus N-linked glycosylation sites are dispensable for viral infectivity. The five consensus N-linked glycosylation sites that are likely to have important roles in infectivity are all located in the amino-terminal half of gp120, indicating that the N-linked glycosylation sites that are important for infectivity of human immunodeficiency virus type 1 are not randomly distributed in gp120. We predict that a partially glycosylated gp120 with most of the dispensable N-linked glycosylation sites removed may be a better vaccine candidate than the fully glycosylated gp120.

Amino Acid Sequence↗

Clinical and histopathologic evaluation of the expression of Ha-ras and fes oncogene products in lung cancer.

The expression of Ha-ras and fes oncogenes was investigated with the immunohistochemical method in formalin-fixed, paraffin-embedded tissue specimens of 147 lung carcinomas. Positive immunoperoxidase reactions for Ha-ras p21 were found in 80.5% of the adenocarcinomas, 39.5% of the squamous cell carcinomas, 21.4% of the large cell carcinomas, and 15.4% of the small cell carcinomas; those for fes P85 were found in 51.2% of the adenocarcinomas, 26.3% of the squamous cell carcinomas, 35.7% of the large cell carcinomas, and 15.4% of the small cell carcinomas. Both Ha-ras p21 and fes P85 were expressed most frequently and most strongly in adenocarcinoma. In addition, adenocarcinoma showed significantly higher incidence of concomitant expression of Ha-ras p21 and fes P85 as compared with other histologic types of lung cancer. Thus, the authors suggest that the cooperative effects of Ha-ras and fes oncogenes are especially important in the carcinogenesis of adenocarcinoma. In adenocarcinoma, the incidence and grade of Ha-ras p21 expression increased with the degree of histologic differentiation, suggesting that Ha-ras oncogene might be related to cellular differentiation. Papillary adenocarcinoma showed more frequent Ha-ras p21 expression in comparison with acinar adenocarcinoma. In well- or moderately differentiated adenocarcinoma, the incidence and grade of Ha-ras p21 immunoreactivity in the cases with poor prognosis were significantly higher than in those with good prognosis if other major prognostic factors were equivalent in the two groups. The authors propose that the expression of Ha-ras p21 may be one of the useful prognostic factors in such carcinomas.

Adenocarcinoma↗