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Biomedical subjects

M Kawabata

Publications and source records attributed to M Kawabata.

At least 181 records · Page 10Linked to original sources

Affinity purification of macrophage migration inhibitory factor/glycosylation inhibiting factor (MIF/GIF) from bovine brain by using a peptide ligand derived from a novel serpin.

We purified macrophage migration inhibitory factor/glycosylation inhibiting factor (MIF/GIF) from bovine brain by using an affinity column with the C-terminal region peptide of a novel serpin as a ligand. The affinity purified preparation showing a single band on SDS-PAGE contained four peptides on RP-HPLC, which were converged into two peptides time-dependently. Sequence analysis and Western blotting revealed that one was identical to bovine MIF/GIF and the other was an N-terminally modified form of MIF/GIF. These results indicated that there exist at least two forms of MIF/GIF in the bovine brain and that they have an affinity for the C-terminal portion of the serpin.

Amino Acid Sequence↗

Therapeutic trials in 200 patients with HTLV-I-associated myelopathy/ tropical spastic paraparesis.

We report here the results of therapeutic trials in 200 patients with HTLV-I-associated myelopathy (HAM)/tropical spastic paraparesis (TSP) conducted in our department between 1986 and 1993. Motor disability grades were improved by more than one grade in 69.5% (91/131) of patients by oral administration of prednisolone, 50% (3/6) by eperisone hydrochloride only, 43.8% (7/16) by blood purification (lymphocytapheresis and plasmapheresis), 40.0% (2/5) by intrathecal injection of hydrocortisone, 30.0% (3/10) by intravenous injection of high-dose methylprednisolone, 23.3% (10/43) by interferon-alpha (intramuscular injection and inhalation), 22.2% (2/9) by azathioprine, 20.0% (4/20) by high-dose vitamin C, 16.0% (4/25) by erythromycin, 12.5% (3/24) by salazosulfapyridine, 11.8% (2/17) by mizoribine, 7.1% (1/14) by fosfomycin, and 6.3% (1/16) by thyrotropin releasing hormone. No critical side effects of these therapies were seen with the exceptions of one patient with adult respiratory distress syndrome due to cytomegalovirus infection and one patient with drug-induced hepatitis/hepatic failure. Selection of these treatments for patients with HAM/ TSP must be considered on the basis of age, sex, disease severity and complications to reduce adverse events and to improve quality of life. Although the results were a synopsis of different treatments given to 200 patients with HAM/ TSP as an open trial, we consider this the first report of a large-scale therapeutic trial in patients with HAM/TSP. The results of this study indicate that immunomodulatory therapies have some beneficial effects in HAM/TSP, and the functions of these agents are related to the pathophysiology of this disease.

Administration, Oral↗

Role of endogenous endothelin and nitric oxide in tubuloglomerular feedback.

To elucidate the roles of endogenous endothelin (ET) and nitric oxide (NO) in tubuloglomerular feedback (TGF), the effects of FR139317, a specific ET-A receptor antagonist, and NG-nitro-L-arginine (L-NNA), a NO synthase inhibitor on TGF were studied in Sprague-Dawley rats. FR139317 (1.5 mg/kg/hr i.v.) reversed the systemic pressor and renal vasoconstrictor responses induced by ET-1 (2 nmol/kg/hr i.v.), but did not alter the early proximal flow rate (EPFR) reduction in response to a loop perfusion with an artificial tubular fluid at 40 nl/min (47 +/- 3 vs. 47 +/- 3% in controls). L-NNA (0.2 mg/kg + 2 micrograms/kg/min i.v.) had no effect on systemic blood pressure (BP), renal hemodynamics or EPFR measured at zero perfusion (31 +/- 2 vs. 31 +/- 2 nl/min in controls), but enhanced the EPFR reduction during loop perfusion to 77 +/- 3%. Loop perfusion with 10(-3) M L-NNA in perfusate also increased the EPFR reduction to 70 +/- 7%. In conclusion, inhibition of NO synthesis enhances the TGF-mediated reduction of nephron GFR. This indicates an active participation of endogenous NO in the control of afferent arteriolar tone. endogenous ET does not influence TGF via the ET-A receptor.

Animals↗

[Long-term effect of transcatheter arterial embolization therapy for renal angiomyolipoma].

We report a case of a 21-year-old man with a right renal angiomyolipoma who has been observed for 20 months after successful treatment with selective transcatheter arterial embolization (TAE). In May 1993, he was transferred to our hospital for the treatment of an abdominal mass. Examination revealed a solid and fat-containing right renal tumor on computed tomography (CT) and magnetic resonance imaging (MRI), hypervascular staining with multiple peripheral microaneurysms on renal angiogram, indicating an angiomyolipoma (AML). He did not have any signs of tuberous sclerosis. Because he complained of abdominal pain and the tumor was 9 cm in diameter, TAE of the tumor using polyvinyl alcohol foam was performed to prevent life-threatening hemorrhage. Renal angiogram after TAE demonstrated a complete shut-down of blood supply to the tumor and CT scan, 6 and 20 months after TAE, demonstrated a decrease in size to 4.5 cm in diameter, showing a favorable long-term effect of treatment. He has been symptom-free for 20 months. TAE appears to be a safe and effective treatment for AML, preventing tumor growth and thus possibly hemorrhage or rupture of the tumor over the long -term.

Adult↗

[Clinical features of allergic granulomatosis and angiitis (Churg-Strauss syndrome). Association with asthma symptoms].

We reported clinical and laboratory findings of 5 patients with Churg-Strauss syndrome (CSS), especially association with asthma symptoms. Subjects included 3 males and 2 females with a mean age of 53.8 year-old. In all 5 patients symptoms of neuropathy; mononeuritis multiplex and in some patients, other vasculitic symptoms; fever, diarrhea, abdominal pain and skin eruptions, were noted. These clinical features and laboratory findings; marked peripheral eosinophilia and elevation of serum ECP were normalized after steroid therapy. We investigated the relation between the occurrence of CSS and the symptoms of asthma. The mean duration of asthma in this series was 17.2 years, and 4 cases were atopic and one was non-atopic asthma. In previous publications, asthmatic symptoms were severe at the onset of the disease and progressed thereafter. In our 5 cases, however, the severities of bronchial asthma were mild of two cases, moderate of two and severe of only one, moreover severe asthmatic attacks were shown in only 2 cases when the manifestation of systemic vasculitis occurred. In conclusion, although CSS has been thought that one of complications of bronchial asthma, the occurrence of CSS are not necessarily correlated with symptoms of bronchial asthma.

Adult↗

Interaction of the transforming growth factor-beta type I receptor with farnesyl-protein transferase-alpha.

Transforming growth factor-beta 1 (TGF-beta 1) is the prototype of a large family of molecules that regulate a variety of biological processes. The type I (T beta R-I) and type II (T beta R-II) receptors for TGF-beta 1 are transmembrane serine/threonine kinases, forming a heteromeric signaling complex. Recent studies have shown that T beta R-II is a constitutively active kinase and phosphorylates T beta R-I upon ligand binding, suggesting that T beta R-I is the effector subunit of the receptor complex, which transduces signals to intracellular targets. This model has been further confirmed by the identification of constitutively active T beta R-I that mediates TGF-beta 1-specific cellular responses in the absence of ligand and T beta R-II. To investigate signaling by TGF-beta 1, we have sought to isolate proteins that interact with the cytoplasmic region of T beta R-I. One of the proteins identified was the alpha subunit of farnesyl-protein transferase (FT alpha) that modifies a series of peptides including Ras. T beta R-I specifically interacts with FT alpha in the yeast two-hybrid system. Glutathione S-transferase-T beta R-I fusion proteins bind FT alpha translated in vitro. T beta R-I also phosphorylates FT alpha. We further show that the constitutively active T beta R-I interacted with FT alpha very strongly whereas an inactive form of T beta R-I did not. These results suggest that FT alpha may be one of the substrates of the activated T beta R-I kinase.

Activin Receptors, Type I↗

A novel serpin-like protein, B-43, exists in both neurons and astrocytes: an immunohistochemical study in the parietal region of the bovine brain.

The presence of a novel member of serine proteinase inhibitor, B-43, was immunohistochemically indicated in both neurons and astrocytes in the parietal region of the bovine brain. B-43-like immunoreactivity was detected in pyramidal cells in the cortex and GFAP-positive astroglial cells in the white matter. The processes of B-43 may play a cooperative role with glia-derived nexin/protease nexin-1 and alpha 1-antichymotrypsin in the brain.

Animals↗

Effect of balloon occluded arterial infusion of anticancer drugs on the prognosis of cervical cancer treated with radiation therapy.

PURPOSE: The effect of local injection of anticancer drugs by balloon catheter, i.e., balloon occluded arterial infusion (BOAI), on the prognosis of cervical cancer treated with radiotherapy were retrospectively estimated. METHODS AND MATERIALS: Sixty-five patients with cervical cancer (Stage I-IV) treated by irradiation were included in the study. Among the 65 cases, 2 were in Stage I, 13 in Stage II, 40 in Stage III, and 10 in Stage IV. Patients who received surgical resection were excluded. Thirty-nine patients received BOAI and 44 received brachytherapy. Twenty-six patients were not indicated for BOAI because of insufficient renal function, hepatic complications, hematological complications, and refusal from the patients. Cisplatin (0.9-1.7 mg/kg), Adriamycin (0.7-0.9 mg/kg), and Pepleomycin (0.4-0.6 mg/kg) were administered simultaneously into the bilateral internal iliac arteries by BOAI. External irradiation was given by 10 MV x-ray. Total dose administered to the regional lymph nodes by the external irradiation was 48.3 +/- 8.7 Gy. Radium was used at brachytherapy. The dose delivered by the brachytherapy at point A was 45.3 +/- 14.9 Gy. Patients without brachytherapy received 26.1 +/- 19.1 Gy of boost irradiation by the external photon beam. The survival probabilities of the patients were calculated by Kaplan-Meier method. RESULTS: The 5-year survival rates of the Stage III patients with and without BOAI were 53 +/- 13% and 24 +/- 18%, respectively (p = 0.036). By multivariate analyses using Cox's proportional hazard model, stage and BOAI were selected as significant predictors of the prognosis. Transient bone marrow suppression was observed in about half of the patients with BOAI. No significant increase of the incidence of the late radiation damage by BOAI in rectum or in urinary bladder was observed. CONCLUSION: Balloon occluded arterial infusion of anticancer drugs may improve the prognosis of the patients with cervical cancer without increasing the incidence of the late radiation damage. A larger scale prospective randomized study is desired.

Actuarial Analysis↗

Phosphorylation-dependent interaction of the cytoplasmic domains of the type I and type II transforming growth factor-beta receptors.

Transforming growth factor-beta (TGF-beta) transduces signals through its type I and type II receptors. Both receptor types have previously been shown to interact in a heteromeric complex in the presence of TGF-beta. We have now characterized these interactions between both receptor types using a combination of yeast two-hybrid interaction assays and coimmunoprecipitation analyses. Our results indicate a direct association between the cytoplasmic domains of the two receptor types. Mutation analysis of these cytoplasmic domains reveals that this direct interaction requires kinase activity and, thus, depends on phosphorylation, probably via a transphosphorylation mechanism. Furthermore, the two receptor types already have an inherent affinity for each other in the absence of TGF-beta, and the heteromeric complex can be detected in coimmunoprecipitations under these conditions. Taken together, our results reveal a novel mechanism of receptor complex formation, whereby two different cytoplasmic domains directly associate with each other. This interaction may play a major role in activation of serine/threonine kinase receptors.

Amino Acid Sequence↗

Overexpression of the c-Myc oncoprotein blocks the growth-inhibitory response but is required for the mitogenic effects of transforming growth factor beta 1.

One of the more intriguing aspects of transforming growth factor beta 1 (TGF beta 1) is its ability to function as both a mitogenic factor for certain mesenchymal cells and a potent growth inhibitor of lymphoid, endothelial, and epithelial cells. Data are presented indicating that c-myc may play a pivotal role in both the mitogenic and antiproliferative actions of TGF beta 1. In agreement with previous studies using C3H/10T1/2 fibroblasts constitutively expressing an exogenous c-myc cDNA, we show that AKR-2B fibroblasts expressing a chimeric estrogen-inducible form of c-myc (mycER) are able to form colonies in soft agar in the presence of TGF beta 1 only when c-myc is activated by hormone. Whereas these findings support a synergistic role for c-myc in mitogenic responses to TGF beta 1, we also find that c-myc can antagonize the growth-inhibitory response to TGF beta 1. Mouse keratinocytes (BALB/MK), which are normally growth-arrested by TGF beta 1, are rendered insensitive to the growth-inhibitory effects of TGF beta 1 upon mycER activation. This ability of mycER activation to block TGF beta 1-induced growth arrest was found to occur only when the fusion protein was induced with hormone in the early part of G1. Addition of estradiol late in G1 had no suppressive effect on TGF beta 1-induced growth inhibition.

Animals↗

Cloning of a novel type II serine/threonine kinase receptor through interaction with the type I transforming growth factor-beta receptor.

The transforming growth factor-beta (TGF-beta) superfamily comprises a number of molecules that are involved in a wide variety of biological processes. Specific receptors for several members of this family have been molecularly identified, forming a new category of transmembrane serine/threonine kinase receptors. The type I and type II receptor interact both physically and functionally, thereby cooperating to generate intracellular signals. The yeast two-hybrid system was used to identify proteins that can interact with the cytoplasmic region of the type I TGF-beta receptor. One of the proteins identified encodes a novel putative serine/threonine kinase receptor. Sequence analysis suggests that this molecule belongs to the type II receptor class. This receptor, however, is distinct from other type II receptors in having an extraordinarily long C-terminal tail region. The pattern of expression in adult tissues is different from that of other known type II receptors; it is highly expressed in heart and liver. In the yeast system, the cytoplasmic regions of different combinations of type I and type II receptors heterodimerize, providing a new cloning strategy for the large number of serine/threonine kinase receptors likely to exist for the many ligands of the TGF-beta superfamily.

Activin Receptors↗

Purification of ginger proteases by DEAE-Sepharose and isoelectric focusing.

Ginger proteases in ginger rhizome (Zingiber officinale roscoe) were extracted from the ginger acetone powder and purified on DEAE-Sepharose and Sephadex G-75 columns. Before the purification, excess p-chloromercuribenzoate was added to the enzymes to prevent their autodigestion. The mercuribenzoate-proteases were further purified and fractionated by isoelectric focusing in Ampholine of pH 3-10 or pH 4-6. The proteases were fractionated into three components by the isoelectric focusing, having pI value of 4.5, 4.6 and 4.8 respectively. All these proteases had a molecular mass of 29,000 as measured by SDS-polyacrylamide gel electrophoresis and by TSK G2000SW XL gel chromatography. The Ampholine in the purified enzymes can quickly be removed by the gel chromatography of TSK G2000SW. Some divalent metal ions, such as Hg2+, Cu2+, Cd2+, and Zn2+, strongly inhibited these purified enzymes.

Endopeptidases↗

Improved chromatographic purification of human and bovine type V collagen sub-molecular species and their subunit chains from conventional crude preparations. Application to cell-substratum adhesion assay for human umbilical vein endothelial cell.

Two human type V collagen sub-molecular species, designated [alpha 1(V)]2 alpha 2(V) and alpha 1(V)alpha 2(V)alpha 3(V), were purified chromatographically from a commercially available preparation, in which cystine-rich collagenous contaminants were contained, with a column packed with Fractogel EMD SO3-. From bovine crude preparations, the [alpha 1(V)]2 alpha 2(V) form free from the collagenous contaminants was purified. Type V collagen subunit chains were isolated from each type V collagen molecule by anion-exchange HPLC with a Bakerbond PEI Scout column. The highly purified human type V collagen molecules and their subunit chains were used to examine the inhibitory effect on human umbilical vein endothelial cell proliferation. It was confirmed that the alpha 1(V) chain has inhibitory activity and it was found that the inhibitory effect of the [alpha 1(V)]2 alpha 2(V) form is stronger than that of the alpha 1(V)alpha 2(V)alpha 3(V) form and that the alpha 3(V) chain has no inhibitory activity.

Animals↗

Purification of a novel serpin-like protein from bovine brain.

We purified a novel serine proteinase inhibitor (serpin)-like protein from the bovine brain and named it B-43 from its molecular mass, 43 kDa. A cleaved peptide from B-43 was copurified with the native B-43. Partial amino acid sequencing of the purified B-43 showed that this protein was homologous to glia-derived nexin/protease nexin-1 (GDN/PN-1), plasminogen activator inhibitor 2, leukocyte elastase inhibitor (LEI) and placental thrombin inhibitor (PTI) among the serpins. Although B-43 had a similar amino acid composition to these serpins, the biochemical features of B-43 were different from them. B-43 did not form sodium dodecyl sulfate (SDS)-resistant serpin-proteinase complexes with thrombin, urokinase, pancreatic elastase and plasmin, suggesting that these proteinases were not the targets of B-43. In contrast to GDN/PN-1, B-43 did not have an affinity for heparin. B-43, having different biochemical properties from GDN/PN-1, appears to be an additional serpin expressed in the brain.

Amino Acid Sequence↗

Paget sarcoma of the cervical vertebrae: an autopsy case report and review of the literature.

A 69 year old Japanese woman was hospitalized for emergency treatment of sudden onset of tetraplegia and somnolence. The patient had a long history of occipital pain without definite diagnosis. After admission, the patient progressively developed generalized palsy including respiratory paralysis, and died of bronchopneumonia. Autopsy revealed osteosarcoma of the cervical vertebrae with the features of Paget's disease involving the skull and the cervical vertebrae. Paget sarcoma is rare in Japan, where Paget's disease of the bone is an uncommon condition. A review of the world literature failed to reveal any reports describing Paget sarcoma of the cervical vertebrae. The present report indicates that the development of Paget sarcoma in the upper cervical vertebrae may cause life-threatening neurologic complications.

Aged↗

Plasma granulocyte colony stimulating factor concentrations in pregnant women.

We measured the plasma granulocyte colony stimulating factor (G-CSF) concentrations in pregnant women to evaluate the association between G-CSF and increased neutrophil counts that has been observed during pregnancy. We examined 96 pregnant and 10 nonpregnant women. The G-CSF concentrations were assayed using a sandwich enzyme immunoassay. The G-CSF concentrations in pregnant women were significantly higher at all times than those of nonpregnant women. The G-CSF concentrations were also significantly higher during than before labor. The plasma G-CSF concentrations were positively correlated with the neutrophil counts during the 3rd trimester only. In conclusion, increased G-CSF concentrations may be related to the increases in neutrophil counts in pregnant women, especially during the 3rd trimester.

Adult↗