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Biomedical subjects

M Matsui

Publications and source records attributed to M Matsui.

At least 325 records · Page 18Linked to original sources

Gene cloning and expression of a bone morphogenetic protein derived from a murine osteosarcoma.

Based on information from partial amino acid sequences of a protein with bone-inducing activity that was purified from a murine osteosarcoma (Dunn type), a cDNA library of the sarcoma was screened to clone a gene complementary to the protein. The cloned cDNA was amplified and transfected into Chinese hamster ovarian (CHO) cells for expression. When the protein produced by the transfected cell line was implanted in combination with pure carrier collagen into allogeneic mice, ectopic ossicles consistently developed at implanted sites within two weeks. The nucleotide sequence of the cDNA and its deduced amino acid sequence were homologous to those of human bone morphogenetic protein-4 (also BMP-2B). In addition, the cDNA and deduced amino acid sequences were identical to those proposed for murine BMP-4 derived from the normal murine fetus. It is postulated that the cloned cDNA encodes the protein responsible for bone formation induced by implantation of devitalized Dunn-type osteosarcoma tissue or cells. The protein product was identified as murine BMP-4, a member of the TGF-beta gene family.

Amino Acid Sequence↗

[A case of Crow-Fukase syndrome associated with chronic pachymeningitis].

A 34-year-old woman was admitted to our hospital in 1991, because of progressive headache, nausea and generalized edema. She was diagnosed as Crow-Fukase syndrome associated with plasma cell dyscrasia (IgA lambda type) in 1987, presenting with polyneuropathy, edema, and dermatologic changes. Those manifestations were improved with irradiation and corticosteroids, but headache, nausea and generalized edema gradually developed after the discontinuation of corticosteroid therapy in 1991. On admission, marked bilateral papilledema was noted but fever and meningeal irritation signs were absent. A spinal tap showed a clear cerebrospinal fluid (CSF) with an open pressure of more than 400 mmH2O, normal cell count, total protein level of 87 mg/dl, and IgG level of 12.3 mg/dl. The CSF culture for microorganisms was negative and the cytological study of CSF also was normal. De novo synthesis rate of CSF IgG was markedly elevated (35.3 mg/day). MRI of the head using Gd-DTPA revealed diffuse hypertrophic dura mater, which made the diagnosis of chronic pachymeningitis. Cerebral angiographies were normal. An RI cisternography demonstrated delayed absorption of the CSF without ventricular reflux. Gallium and bone scintigrams did not show any pathological accumulation of the isotopes in the head. The lack of abnormalities causing chronic pachymeningitis in this case suggests that the chronic pachymeningitis might be associated with Crow-Fukase syndrome. The development of increased intracranial pressure is not rare in Crow-Fukase syndrome but the etiology remained unknown in most cases. We therefore suggest that MRI study with contrast enhancement should be performed in cases of this condition with increased intracranial pressure.

Adult↗

[An immunopathological study during steroid-responsive and steroid-nonresponsive stages on a patient with neuro-Behçet's disease].

We followed up the clinical course and changes of brain magnetic resonance imaging (MRI) findings in a case of neuro-Behçet's disease, and performed serial immunological examinations of the cerebrospinal fluid (CSF). On the two episodes of acute exacerbation, gadolinium (Gd)-enhancement effects on brain MRIs were observed in the brain stem and the deep white matter of cerebral hemispheres. The CSF abnormality of this period was characterized by increases in proportions of polymorphonuclear leukocytes and intrathecal IgG synthesis in addition to the findings suggesting breakdown of the blood brain barrier (BBB). These findings disappeared in parallel with clinical improvement by corticosteroid therapy. In contrast, during a subsequent chronic progressive stage, steroid-resistant neuropsychiatric symptoms and an absence of Gd-enhancement effects on brain MRIs were observed despite progressive breakdown of BBB. These findings suggest that neuro-Behçet's disease should comprise two distinct immunopathogenetic stages, that is, a relatively early steroid-responsive stage with a relapsing-remitting clinical course and a late steroid-nonresponsive stage with a chronic progressive course.

Behcet Syndrome↗

[Multidisciplinary treatment of advanced invasive thymoma].

From February 1988 to September 1992, six patients with Stage III or IV invasive thymoma were enrolled onto our study of multidisciplinary treatment, which included chemotherapy, surgery, and radiotherapy. The chemotherapy consisted of cisplatin (20 mg/m2 continuous 24-hour infusion on days 1 through 4), doxorubicin (40 mg/m2 on day 1), and methylprednisolone (1,000 mg on days 1 through 4 and 500 mg days 5 and 6). Two patients received surgery (incomplete resection) and postoperative chemo/radiotherapy, and four patients received induction chemotherapy followed by surgery and chemo/radiotherapy. All patients with induction chemotherapy showed a partial response and underwent complete (n = 2) or partial (n = 2) resection. Four patients are alive with no evidence of disease for 31 to 55 months after the diagnoses. But two with partial resection after chemotherapy died of recurrent disease. Multidisciplinary treatment including chemotherapy may be a new therapeutic choice in management of advanced invasive thymoma.

Adult↗

[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↗

[The sub-classification of pre-proliferative diabetic retinopathy].

The authors divided 155 eyes (106 cases) affected by pre-proliferative diabetic retinopathy into three sub-groups according to the severity of retinopathy and followed them for one year. The criteria for and numbers of eyes in each group were as follows; 1) mild type with soft exudate and without apparent non-perfused areas on fluorescein angiography (39 eyes). 2) moderate type with soft exudate and demonstrable non-perfused areas (103 eyes). 3) severe type with soft exudates, non-perfused areas and venous beading (13 eyes). The proportion undergoing photocoagulation was 23% in the mild type, 81% in the moderate type and 100% in the severe type. None of the eyes in the mild type underwent photocoagulation unless they advanced to a more severe type. Nine eyes of the mild type which progressed to moderate type during the follow-up period underwent focal photocoagulation. Panretinal photocoagulation was performed in 29% of moderate type eyes and 77% of severe type eyes. The courses of these three sub-groups were analyzed after one year of follow up. The proportion developing proliferative retinopathy was 0% in mild type, 17% in moderate type and 46% in severe type. Based on the above results, we conclude that the sub-classification we propose in this paper can be applied in managing patients with pre-proliferative diabetic retinopathy.

Diabetic Retinopathy↗

Purification and characterization of a bone-inducing protein from a murine osteosarcoma (Dunn type).

A protein fraction capable of eliciting cartilage or bone formation in vivo was purified more than 100,000-fold from a murine osteosarcoma (Dunn type). Intramuscular implantation of as little as 20 ng of the purified protein with 2 mg of pure skin collagen consistently induced ectopic new bone formation. The apparent molecular size of the purified protein was 32 kd on sodium dodecylsulfate-polyacrylamide gel electrophoresis. On reduction, the 32-kd protein split into subunits with the same partial amino acid sequences, and these partial sequences were identical to those of human bone morphogenetic protein-2B (BMP-4) which is assumed to be a member of the transforming growth factor-beta superfamily.

Amino Acid Sequence↗

COP1, an Arabidopsis regulatory gene, encodes a protein with both a zinc-binding motif and a G beta homologous domain.

Plant seedling development is capable of following 1 of 2 distinct morphogenic pathways: skotomorphogenesis in darkness and photomorphogenesis in light. Dark-grown Arabidopsis seedlings with recessive mutations at the constitutively photomorphogenic (COP1) locus indicate that the wild-type COP1 protein represses photomorphogenesis in darkness and that light reverses this repressive activity. Using a T-DNA-tagged mutant, we have cloned the COP1 locus. The amino-terminal half of the encoded protein contains a conserved zinc-binding motif, whereas the carboxyl-terminal half contains a domain homologous to the WD-40 repeat motif of G beta proteins. The presence of both a putative DNA-binding motif and a G protein-related domain in a single polypeptide suggests that COP1 may be the first of a new class of regulatory molecules. This novel structure could endow COP1 with the capacity to function as a negative transcriptional regulator capable of direct interaction with components of the G protein signaling pathway.

Amino Acid Sequence↗

Immunochemical characterization of developmental changes in rat hepatic hydroxysteroid sulfotransferase.

A major isoenzyme of hepatic androsterone-sulfating sulfotransferase (AD-ST) was purified from adult female rats. The activity was purified 122-fold over that found in the cytosol and showed a single protein band with a subunit molecular mass of 30 kDa after sodium dodecyl sulfate polyacrylamide gel electrophoresis. The purified enzyme exhibited four isoelectric variants of subunits on denaturing isoelectrofocusing gels (pI = 5.8, 6.1, 6.7 and 7.2). Rabbit antiserum raised against the enzyme specifically detected AD-ST polypeptide in rat liver cytosol. Immunoblot analysis of liver cytosol from female and male rats at various ages showed good correlation between the levels of AD-ST activity and AD-ST polypeptide. Significant levels of AD-ST activity and polypeptide were detected in senescent male rats, though normal adult male rats have very low levels of AD-ST activity and protein. The relative content of the isoelectric variants of AD-ST were different in liver cytosol of weanling and adult females, indicating that age- and gender-related alterations of hepatic AD-ST activity are primarily determined by the levels of AD-ST polypeptide and the relative amounts of the four isoelectric variants of the enzyme.

Aging↗

Differential localization of sulfotransferase isoenzymes in rat liver.

Liver sections prepared from male and female rats were immunohistochemically stained with the antisera against phenol sulfotransferase G (P-STG), an isoenzyme of phenol ST as well as androsterone-sulfating ST (AD-ST), an isoform of hydroxysteroid ST. Localization of these isoenzymes in liver is sex-dependent and is markedly different between the two. P-STG is preferentially localized in the hepatocytes proximal to the central vein in females, whereas it is present in all the hepatocytes throughout the liver in males. On the other hand, AD-ST is evident in the hepatocytes proximal to the portal triad in males, while in females it is synthesized and localized in all the hepatocytes. The polarized sex-related localization of these ST isoenzymes appears to correlate with differential hormonal regulation of the enzymes.

Animals↗

Effect of tumor size on the enhancement by gamma interferon of the localization of radiolabeled F(ab')2 fragments of anti-intercellular adhesion molecule-1 monoclonal antibodies in human colon carcinoma cells grafted in nude mice.

Because tumor size has been shown to influence the specific accumulation of radiolabeled anti-tumor-associated antigen monoclonal antibodies (mAb), the present study has investigated the effect of the tumor size on the enhancement by gamma interferon (IFN-gamma) of the accumulation of radiolabeled mAb in malignant lesions. Intercellular adhesion molecule-1 (ICAM-1) has been used as a marker because of its high susceptibility to modulation by IFN-gamma. F(ab')2 fragments of anti-ICAM-1 mAb CL207.14 have been selected to visualize malignant lesions, because they had been shown to be more sensitive probes for our experiments than whole IgG. Administration of IFN-gamma to human colon carcinoma-bearing nude mice increased the expression of ICAM-1 in the xenografts and the specific accumulation of 125I-F(ab')2 fragments of anti-ICAM-1 mAb CL207.14. The latter effect is influenced by the size of the lesions, because it was observed only in tumors with an approximate diameter of 8 mm and an approximate weight of 250 mg. If these results obtained in an animal model system are applicable to patients with malignant diseases, the present investigation suggests that administration of IFN-gamma enhances the sensitivity of immunoscintigraphy and the efficacy of immunotherapy with radiolabeled mAb which recognize tumor-associated antigens that are susceptible to modulation by IFN-gamma. However, the effect of IFN-gamma is not a general phenomenon but is influenced by the size of the malignant lesions.

Animals↗

Large deletion of androsterone UDP-glucuronosyltransferase gene in the inherited deficient strain of Wistar rats.

LA Wistar rats have a deficiency of androsterone UDP-glucuronosyltransferase (UDPGT) and are present in Wistar rat colonies around the world. In order to clarify the molecular mechanism of the deficiency, androsterone UDPGT cDNA clone, pGT2 was isolated from rat liver cDNA library and was digested with restriction enzymes to afford three probes for Northern and Southern blot analyses in HA (normal), heterozygous LA and LA Wistar rats. In Northern blot analysis, androsterone UDPGT mRNA was totally absent in LA Wistar rat liver. Southern blot analysis suggested a large deletion of androsterone UDPGT gene in the rats. Genomic DNA amplifications with synthetic primers which have nucleotide sequences corresponding to the 5'-region of androsterone UDPGT cDNA, suggested that androsterone UDPGT gene has exon 1 with a length of some 700 bp and that this exon is deleted in LA Wistar rats. Based on these lines of evidence, it is concluded that the large portion of androsterone UDPGT gene is deleted in LA Wistar rats, which results in the absence of androsterone UDPGT mRNA and consequently the corresponding enzyme protein.

Animals↗

Difference in tumor incidence and other tissue responses to polyetherurethanes and polydimethylsiloxane in long-term subcutaneous implantation into rats.

The long-term (1- and 2-year) adverse tissue responses including tumor formation by subcutaneous implantation of polyurethanes (PUs) and silicone (Sil) films into rats were compared. The weight-averaged molecular weights (Mw) of the PUs prepared from 4,4'-diphenylmethanediisocyanate, poly(tetramethyleneglycol) of Mn = 1000 and 1,4-butanediol are 220,000 (U-4), 124,000 (U-6), and 55,600 (U-8). The 50:50 mixed film of U-6 and silicone (U-6/sil) was prepared by roll-mixing of the noncured silicone and the U-6 solution followed by evaporation of the solvent and heat-curing at 70 degrees C. The tissue responses around implants were classified into four groups as follows: (A) tumor, (B) atypical cell proliferation accompanied by preneoplastic changes, (C) cell proliferation without preneoplastic changes, (D) no obvious responses. In both implantation periods, the PUs gave higher incidents of the adverse responses including tumor formation in comparison to Sil. No significant molecular weight-dependent trend was found in a 1-year study using U-4, 6, and 8. Significant PU-dose-dependent trends were found in a 2-year study: the total active incidence (A+B+C), U-6(22/29) greater than U-6/sil(11/29) greater than sil(7/28); tumor incidence (A), U-6(11/29) greater than U-6/sil(2/29) = sil(2/28). No detectable amounts of 4,4'-methylenedianiline (MDA) were found in the PUs. The methanol extracts from the PUs were negative in the mutagenicity tests. These indicate no relationship between the tumor formation by the PU films and the mutagenicities of the chemicals (mainly oligomers) leached from the PUs.

Aniline Compounds↗

The prognosis of patients with gastric cancer possessing sex hormone receptors.

Estrogen receptors (ER) and progesterone receptors (PgR) were immunohistologically investigated in 107 patients with gastric cancer who underwent curative resection. Both ER and PgR were detected only in the cancer cell nucleus. The ER positive rate was 27.7% for males and 31.0% for females, while the PgR positive rate was 9.2% for males and 11.9% for females. Clinicopathologically, the ER positive rate was slightly higher in young females and in cases of poorly differentiated gastric cancer. When cumulative survival rates were analyzed in relation to the presence or absence of receptors, the 10-year cumulative survival rate after surgery was significantly lower in the ER positive cases, being 15.7% cent, than in the ER negative cases, being 62.7%, and also significantly lower in the PgR positive cases, being 18.2%, than in the PgR negative cases, being 48.3%. The coexistence of ER and PgR in gastric cancer tissues suggests that the ER is physiologically active, or that ER positive gastric cancer is hormone-dependent. The poor prognosis of patients with receptor positive gastric cancer suggests that gastric cancer with these receptors is highly malignant.

Female↗