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Biomedical subjects

M Kawabata

Publications and source records attributed to M Kawabata.

At least 145 records · Page 8Linked to original sources
PubMed1998

[A case of pulmonary infiltration with eosinophilia caused by Ascaris suum].

A 46-year old man was admitted to our hospital with dry cough and diarrhea. His chest CT showed diffuse subpleural small nodular shadows. Eosinophilia and an increase of serum IgE were detected. Eosinophils were also increased in BALF. An antibody against Ascaris suum was positive in serum while other causes of eosinophilia (e. g., drugs, fungus, collagen disease) were absent. Ivermectin was administered and the diarrhea improved within 3 days. The abnormal chest shadows and dry cough disappeared 3 months later. Pulmonary infiltration with eosinophilia (PIE) syndrome caused by Ascaris suum was diagnosed because of the clinical course and serum examination results. Recently, zoonoses are increasing with the boom of oversea travel and "natural" foods. We report a case of PIE syndrome caused by Ascaris suum and describe the clinical features and the social significance including the origin of this disease.

Animals↗
PubMed1998

[A case of pleuritis caused by strongyloides in a carrier of T-cell lymphoma virus type I (HTLV-I)].

A 73-year-old woman was admitted to our hospital complaining of dyspnea, fever and general edema. Chest roentgenogram showed bilateral pleural effusion and cardiomegaly. Cardiovascular examination demonstrated atrial tachycardia and left ventricle dysfunction, suggesting congestive heart failure. She was sero-positive for human T-cell lymphoma virus I (HTLV-I). The dyspnea and general edema improved after therapy for heart failure. Because the pleural effusion persisted after therapy, thoracentesis was performed. The pleural effusion was an exudate, and Strongyloides sterocoralis was detected by microscopy. Two courses of thiabendazole (1,500 mg/day, 3 days) were given orally. After this therapy, the pleural effusion improved markedly. This case suggests that Strongyloides stercoralis may be a causative agent of pleuritis in HTLV-I endemic areas.

Aged↗
PubMed1998

[Lyme disease].

Lyme disease is a tick-borne disease, and recognized as a complex, multisystem disorder. An outbreak [correction of outback] of Lyme disease was first described in the United States in the 1970s. The presence of Borrelia burgdorferi, its causative agent, in the skin results in the development of characteristic expanding red skin lesions, erythema migrans (EM). EM may be associated with cardiac abnormalities, meningitis, and cranial peripheral neuropathies. Arthritis, neurologic and skin manifestations may persist for several years and become chronic in a small percentage of patients. Studies on the classification of B. burgdorferi resulted in the identification of three closely related genospecies, and different clinical manifestation of Lyme disease have been correlated with the infecting genospecies. The diagnosis of Lyme disease should be based primarily on the clinical presentation, epidemiological information and serological tests. Antimicrobials are effective in the treatment of Lyme disease in most patients. Lyme disease is a zoonosis and endemic in areas where suitable mammalian reservoirs for B. burgdorferi and appropriate hosts for the tick vector are present. According to changes in the natural environment, the distribution of infected ticks and reservoirs is anticipated to expand.

Animals↗
PubMed1998

[Pulmonary sclerosing hemangioma with specific CT findings].

A 44-year-old woman was admitted to our hospital for evaluation of an abnormal lung shadow. Chest computed tomography (CT) revealed a tumor surrounded by air-space and an infiltrative shadow in the right S2. Right upper lobectomy was performed and pulmonary sclerosing hemangioma was diagnosed. Usually, pulmonary sclerosing hemangioma shows a solitary round nodule on a chest CT scan. We report a case of pulmonary sclerosing hemangioma with an unusual shadow on a chest CT scan, and review the literature.

Adult↗
PubMed1998

Extracellular matrix production regulation by TGF-beta in corneal endothelial cells.

PURPOSE: Production of extracellular matrix (ECM) by corneal endothelial cells is related to physiologic functions and pathologic conditions and is regulated by many cytokines, including transforming growth factor-beta (TGF-beta). In this study, the molecular mechanism of ECM production regulation by TGF-beta was investigated in cultured corneal endothelial cells. METHODS: The production of ECM components (laminin and fibronectin) was detected in cultured corneal endothelial cells by western blot analysis. To determine the signal transduction pathways, mutant TGF-beta type I receptor (TbetaR-I) and/or Smad protein family members (intracellular signal transducers in TGF-beta signaling) were overexpressed by transfecting their cDNA into the cultured cells, and the effects on ECM production were observed. RESULTS: The production of laminin and fibronectin was stimulated by treatment with TGF-beta1 or TGF-beta2. After transient transfection of cDNA of the constitutively active (CA) mutant of TbetaR-I, the production of laminin and fibronectin was stimulated even in the absence of TGF-beta. The transfection of the dominant negative mutant of TbetaR-I counteracted the effects of TGF-beta. These results confirm that TGF-beta directly stimulates ECM production from corneal endothelial cells through TbetaR-I. The ECM production stimulation by TGF-beta or CA TbetaR-I was accelerated by the overexpression of Smad2, Smad3, and/or Smad4 and inhibited by that of Smad7. These results show that TGF-beta signals connected to ECM production are regulated by Smad family members, located downstream of TbetaR-I. CONCLUSIONS: The results of this study show that TGF-beta stimulates ECM production from corneal endothelial cells through TbetaR-I and Smad family transducers.

Animals↗
PubMed1998

Identification of the granulocyte colony-stimulating factor (G-CSF) producing cell population in human decidua and its biological action on trophoblast cell.

Granulocyte colony-stimulating factor (G-CSF) is a hematopoietic factor, which induces differentiation and proliferation of immature granulocytes. During pregnancy, decidual tissue produces G-CSF and the receptor for G-CSF is expressed on chorionic villous tissues. This study attempted to determine the cell population responsible for G-CSF production in decidual tissue and the influence of G-CSF on trophoblasts. Immunostaining and in situ hybridization showed that both the decidual cells and macrophages in the decidual tissue were sources of G-CSF. With 50 micrograms of G-CSF, the [3H] thymidine uptake was 11,100 +/- 2,200 DPM and the control uptake was 7,970 +/- 1,820 DPM. G-CSF induced proliferation of trophoblasts 1.4-fold higher than that of control. It is concluded that the decidual cells and macrophages were sources of G-CSF in the decidual tissue, and G-CSF promoted trophoblast cell proliferation.

Decidua↗
PubMed1997

A DNA-topoisomerase-II-binding protein with eight repeating regions similar to DNA-repair enzymes and to a cell-cycle regulator.

A two-hybrid system was used to isolate factors that interact with the C-terminal region of DNA topoisomerase IIbeta. A positive clone isolated from a HeLa cDNA library encoded 1522 amino acid residues (molecular mass 170670). The protein, designated topoisomerase-IIbeta-binding protein 1 (TopBP1), interacted with the C-terminal region of topoisomerase IIbeta synthesized in vitro. A database search indicated that TopBP1 possessed eight regions similar to regions of Rad4, Cut5, Ect2, Rev1 and X-ray repair cross-complementing 1 (XRCC1) proteins and a region similar to auto-modification sites of poly(ADP-ribose) polymerase, suggesting that TopBP1 supported catalytic reactions of topoisomerase II through transient breakages of DNA strands.

Amino Acid Sequence↗
PubMed1997

Alteration of cytokine levels by fosfomycin and prednisolone in spontaneous proliferation of cultured lymphocytes from patients with HTLV-I-associated myelopathy (HAM/TSP).

Fosfomycin has recently been reported as an antibiotic with immunomodulatory activities. To evaluate the possibility of clinical administration of fosfomycin in patients with human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP), the effects of this agent on the HTLV-I-induced in vitro phenomenon were studied. The influence of fosfomycin on in vitro spontaneous proliferation (SP) of peripheral blood mononuclear cells (PBMCs) from four patients with HAM/TSP was measured by thymidine incorporation into the cells, and the concentration of several cytokines in the culture supernatants was examined in three HAM/TSP patients. Enzyme-linked immunosorbent assays (ELISAs) were employed to detect the concentrations of interleukin-4 (IL-4), IL-6, IL-10, interferon-gamma (IFN-gamma), transforming growth factor-beta1 (TGF-beta1), and macrophage inflammatory protein-1alpha (MIP-1alpha). The data were compared to the changes by prednisolone which is known to regulate the HTLV-I-associated in vitro phenomenon and to have a therapeutic benefit in patients with HAM/TSP. Production of IL-6, IFN-gamma and MIP-1alpha from the spontaneously proliferating cells were demonstrated. Fosfomycin could not suppress the HTLV-I-associated SP, but had the properties to decrease the levels of TGF-beta1 and MIP-1alpha. It was also demonstrated that the concentrations of IFN-gamma and MIP-1alpha in the cultures in the presence of prednisolone were apparently decreased, suggesting a possible involvement of these cytokines in the pathogenesis of HAM/TSP. These findings support the hypothesis that fosfomycin may have immunomodulatory potentials in HTLV-I-related cellular interactions in a different manner from ordinary immunomodulatory agents.

Adult↗
PubMed1997

Presenilin 1 binds to amyloid precursor protein directly.

Mutations in the presenilin genes are associated with early onset familial Alzheimer's disease and lead to accumulation of beta-amyloid peptide in the brain of patients, suggesting that presenilin abnormalities induce pathological processing of amyloid precursor protein (APP) in Alzheimer's disease. For the understanding of pathogenesis in this type of familal Alzheimer disease, it is important to know whether presenilins are directly involved in the metabolism of beta-amyloid or not. To test whether presenilin 1 (PS1) directly binds to APP, we performed two-hybrid interaction assays between these proteins in yeast cells by using bait plasmids for normal and mutant PS1 and prey plasmids for APP fragments corresponding to the different molecular portions. Positive interaction was observed in any combination between PS1 bait plasmids and APP prey plasmids. Therefore, our results show that PS1 binds to APP directly and suggest that the PS1 protein itself is involved in the metabolism of beta-amyloid peptide.

Alzheimer Disease↗
PubMed1997

Smad6 inhibits signalling by the TGF-beta superfamily.

SMAD proteins have been identified as signalling mediators of the TGF-beta superfamily, which is involved in a range of biological activities including cell growth, morphogenesis, development and immune responses. Smad1, Smad2, Smad3 and Smad5 are ligand-specific: Smadl and Smad5 transduce signals from bone morphogenetic proteins, and Smad2 and Smad3 mediate signalling by TGF-beta and activin, whereas Smad4 acts as a common signalling component. For example, Smad2 is phosphorylated by the TGF-beta type I receptor upon ligand binding, forms a heteromer with Smad4, and then translocates into the nucleus where it activates transcription. Here we report the isolation of Smad6 in the mouse. Smad6 is quite different in structure from the other SMAD proteins, and forms stable associations with type I receptors. Smad6 interferes with the phosphorylation of Smad2 and the subsequent heteromerization with Smad4, but does not inhibit the activity of Smad3. Smad6 also inhibits the phosphorylation of Smad1 that is induced by the bone morphogenetic protein type IB receptor. These data indicate that signals of the TGF-beta superfamily are regulated both positively and negatively by members of the SMAD family.

Amino Acid Sequence↗
PubMed1997

Identification of Smad7, a TGFbeta-inducible antagonist of TGF-beta signalling.

TGF-beta signals from the membrane to the nucleus through serine/threonine kinase receptors and their downstream effectors, termed SMAD proteins. The activated TGF-beta receptor induces phosphorylation of two such proteins, Smad2 and Smad3, which form hetero-oligomeric complex(es) with Smad4/DPC4 that translocate to the nucleus, where they then regulate transcriptional responses. However, the mechanisms by which the intracellular signals of TGF-beta are switched off are unclear. Here we report the identification of Smad7, which is related to Smad6. Transfection of Smad7 blocks responses mediated by TGF-beta in mammalian cells, and injection of Smad7 RNA into Xenopus embryos blocks activin/TGF-beta signalling. Smad7 associates stably with the TGF-beta receptor complex, but is not phosphorylated upon TGF-beta stimulation. TGFbeta-mediated phosphorylation of Smad2 and Smad3 is inhibited by Smad7, indicating that the antagonistic effect of Smad7 is exerted at this important regulatory step. TGF-beta rapidly induces expression of Smad7 mRNA, suggesting that Smad7 may participate in a negative feedback loop to control TGF-beta responses.

Amino Acid Sequence↗
PubMed1997

TGF-beta receptor-mediated signalling through Smad2, Smad3 and Smad4.

Smad family members are newly identified essential intracellular signalling components of the transforming growth factor-beta (TGF-beta) superfamily. Smad2 and Smad3 are structurally highly similar and mediate TGF-beta signals. Smad4 is distantly related to Smads 2 and 3, and forms a heteromeric complex with Smad2 after TGF-beta or activin stimulation. Here we show that Smad2 and Smad3 interacted with the kinase-deficient TGF-beta type I receptor (TbetaR)-I after it was phosphorylated by TbetaR-II kinase. TGF-beta1 induced phosphorylation of Smad2 and Smad3 in Mv1Lu mink lung epithelial cells. Smad4 was found to be constitutively phosphorylated in Mv1Lu cells, the phosphorylation level remaining unchanged upon TGF-beta1 stimulation. Similar results were obtained using HSC4 cells, which are also growth-inhibited by TGF-beta. Smads 2 and 3 interacted with Smad4 after TbetaR activation in transfected COS cells. In addition, we observed TbetaR-activation-dependent interaction between Smad2 and Smad3. Smads 2, 3 and 4 accumulated in the nucleus upon TGF-beta1 treatment in Mv1Lu cells, and showed a synergistic effect in a transcriptional reporter assay using the TGF-beta-inducible plasminogen activator inhibitor-1 promoter. Dominant-negative Smad3 inhibited the transcriptional synergistic response by Smad2 and Smad4. These data suggest that TGF-beta induces heteromeric complexes of Smads 2, 3 and 4, and their concomitant translocation to the nucleus, which is required for efficient TGF-beta signal transduction.

Activin Receptors, Type I↗
PubMed1997

cDNA cloning and genomic organization of the mouse BMP type II receptor.

The cDNA for the mouse bone morphogenetic protein type II receptor (BMPR-II) was isolated using the human counterpart as a probe and its genomic structure was determined. The cDNA encodes a protein of 1,038 amino acids with a single transmembrane domain, a serine/threonine kinase domain, and a long carboxy-terminal tail. The overall amino acid sequence identity between the mouse and the human BMPR-II is 96.6%. mRNA is widely distributed in various adult tissues. The gene is encoded by 13 exons spanning over 80 kb. Two large introns (intron 1 and 3) contribute to the majority of the gene size, as in the mouse activin type II receptor gene. The intron/exon boundaries were sequenced. The results suggest that alternative splicing can yield a shorter form of BMPR-II of 530 amino acids, as reported previously. Knowledge of the structure of the BMPR-II gene is essential for the understanding of the role of bone morphogenetic proteins in the developmental and physiological processes of animals.

Alternative Splicing↗
PubMed1997

Improvement of diagnostic accuracy of transvaginal ultrasound for identification of endometrial malignancies by using cutoff level of endometrial thickness based on length of time since menopause.

Transvaginal ultrasonography (TVS) is considered useful for identifying endometrial malignancies, but it has a low specificity and a high false-positive rate. The purpose of this study was to improve the specificity of this technique. A total of 300 postmenopausal women were studied. They were clinically evaluated by TVS and endometrial histology. Twenty women yielded pathologic findings on endometrial examination. The mean endometrial thickness was related to the length of time since menopause. For endometria with pathological findings, sonographic measurements of endometria with a thickness of greater than 3 mm exhibited 95.0% sensitivity, 68.5% specificity, 19.4% positive predictive value, and 99.4% negative predictive value. If a 4-mm cutoff limit was used for < 5 years since menopause and a 3-mm cutoff limit was used for > or = 5 years since menopause, 95.0% sensitivity, 78.1% specificity, 25.7% positive predictive value, and 99.5% negative predictive value were obtained. The specificity and false-positive rate were improved when the cutoff limit was decided based on the length of time since menopause. The cutoff level of the endometrial thickness for detection of endometrial malignancies should be decided based on the length of time since menopause.

Age Factors↗
PubMed1997

Prospective study to compare endometrial cytology and transvaginal ultrasonography for identification of endometrial malignancies.

We compared transvaginal ultrasonography (TVS) and endometrial cytology by the Endocyte method for endometrial cancer screening. A total of 600 postmenopausal women who hoped for endometrial cancer screening (mean age, 61.1 +/- 8.8 years; range, 44-87 years) underwent TVS, endometrial cytology (Endocyte method), and endometrial histology. The endometrial borders could be visualized by TVS in all women studied. However, cytology could not be performed in 59 women (9.8%) due to cervical stenosis. These 59 women were excluded from further study. Of the 541 remaining women, 38 had pathologic conditions (16 had endometrial cancer and 22 had endometrial hyperplasia). One (6.3%) of the 16 endometrial cancer patients and 10 (45.5%) of the 22 hyperplasia patients were asymptomatic. One hundred thirty-nine (83.7%) of the 166 women with postmenopausal bleeding had no pathological condition. When the cutoff value of endometrial thickness was set at 4 mm for women <5 years since menopause and 3 mm for those > or =5 years since menopause, TVS showed a 97.4% sensitivity, 75.7% specificity, 23.8% positive predictive value, and 99.7% negative predictive value. Thirty-seven of the 38 patients with endometrial disease were detected by TVS. Eight patients with a benign Endocyte examination were found to have endometrial hyperplasia. However, all endometrial cancers were detected by cytological examination. The Endocyte method exhibited 78.9% sensitivity, 95.4% specificity, 56.6% positive predictive value, and an 88.5% negative predictive value. In conclusion, TVS is thought to be useful for identification of patients who required further diagnostic investigation including endometrial histology.

Adult↗
PubMed1997

Sodium phenobarbital-enhanced mutation frequency in the liver DNA of lacZ transgenic mice treated with diethylnitrosamine.

To investigate how a carcinogenic promoter acts on cells mutated by an initiator, we used as a model, lacZ transgenic mouse and a positive selection system. Preliminary data for the mutational events in liver DNA of the mice was generated using diethylnitrosamine (DEN) and sodium phenobarbital (S-PB) as initiator and promoter, respectively. In our first experiment, male MutaMice received a single i.p. injection of saline or 100 mg/kg DEN and were fed a normal diet for 7 days and 500 p.p.m. S-PB in the diet for 21 days. Liver DNA was harvested after a 1 night fast on days 7 and 28 post-DEN treatment. In our second experiment, male mice received a single i.p. injection of phosphate buffered saline or 50 mg/kg DEN and were fed a normal diet for 7 days, a diet with S-PB for 14 days and then a normal diet for 7 days. Liver DNA was harvested after a 1 night fast on days 7, 21 and 28 post-DEN treatment. The S-PB diet enhanced absolute and relative liver weights in all groups. The single intraperitoneal dose of 50 or 100 mg/kg DEN induced high mutation frequencies (MF) in liver, lacZ genes on days 7, 21 and 28. There were no remarkable differences of the MF among any sampling days for animals receiving DEN and a normal diet. S-PB feeding at 500 p.p.m. for 21 days failed to affect the MF in groups given saline or 100 mg/kg DEN. On the other hand, when 50 mg/kg DEN was given, S-PB feeding at 500 p.p.m. for 14 days elevated the MF in liver DNA on days 21 and 28 to approximately 1.8 and 4.0 times the MF, respectively, of the mice fed the normal diet. Consequently, S-PB might preferentially promote certain initiated cells participating in a balance between cell death and proliferation.

Animals↗
PubMed1997

Continuous local injection of carboplatin into the uterine cervix for cervical and endometrial cancer: preliminary study.

Platinum compounds are thought to be concentration- and time-dependent, but intravenous (i.v.) administration does not afford prolonged high platinum concentration in tumor tissue. In order to examine the influence of long-term local continuous (LC) injection of carboplatin, a pharmacokinetic study was performed. Twenty-six patients with uterine cancer were included. I.v. administration (11 patients): carboplatin (210 mg) was given i.v. and samples of target tissue were obtained at operation about 2 or 24 h after administration. LC administration (15 patients): the 21-gauge needle was implanted at the uterine cervix, and carboplatin was injected continuously (30 mg/day) for 3, 7 or 14 days using an external pump. The tissue platinum concentration was measured in the pelvic organs. The mean platinum levels at the cervix and vaginal wall in the LC (7 days) group were higher than those in the i.v. (2 h) group (p < 0.01). With LC injection, sustained platinum levels were maintained in the pelvic organs for a long time, with very few side effects. LC injection may be advantageous on the basis of pharmacokinetics.

Adult↗