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Biomedical subjects

M Kawabata

Publications and source records attributed to M Kawabata.

At least 127 records · Page 7Linked to original sources
PubMed1998

Induction of Smad6 mRNA by bone morphogenetic proteins.

Members of the transforming growth factor-beta (TGF-beta) superfamily transduce signals via Smad proteins. Smad2 and Smad3 mediate TGF-beta signaling, whereas Smad1 and Smad5 transduce bone morphogenetic protein (BMP) signals. Smad4 is a common mediator required for both pathways. Smad6 and Smad7 are recently identified members in the Smad family; they inhibit the signaling activity of the other Smad proteins. Here we show that expression of the Smad6 mRNA is dramatically induced by BMP-2 or osteogenic protein-1 (OP-1)/BMP-7 in various cells. BMP-2 induced expression of Smad7 in one cell type, although much less potently than that of Smad6. Smad6 message was induced by TGF-beta 1 in TGF-beta 1-responsive Mv1Lu cells, but the induction was transient in contrast to the induction by BMPs. These results indicate that Smad6 may form a feedback loop to regulate the signaling activity of BMPs.

Animals↗
PubMed1998

PCR- and ligation-mediated synthesis of marker cassettes with long flanking homology regions for gene disruption in Saccharomyces cerevisiae.

We developed a novel method for synthesizing marker-disrupted alleles of yeast genes. The first step is PCR amplification of two sequences located upstream and downstream of the reading frame to be disrupted. Due to the addition of non-specific single A overhangs by Taq DNA polymerase, each PCR product can be ligated with a marker DNA which has T residues at its 3' ends. After amplification of individual ligation products through the second PCR, both products are mixed and annealed, and the single strand is converted to a double strand by an extension reaction. The final step is PCR amplification of the fragment composed of a selectable marker and two flanking sequences with the outermost primers. This method is rapid and needs only short oligonucleotides as primers.

DNA Ligases↗
PubMed1998

Signal transduction by bone morphogenetic proteins.

Bone morphogenetic proteins (BMPs) are multifunctional cytokines, which are members of the transforming growth factor-beta (TGF-beta) superfamily. Activities of BMPs are extracellularly regulated by BMP-binding proteins, Noggin and Chordin. BMPs bind to two different types of serine-threonine kinase receptors, type I and type II. Two BMP type I receptors and a BMP type II receptor have been identified in mammals. Intracellular signals are transduced by Smad proteins. Smad1, Smad5 and probably MADH6, are activated by BMP receptors, form heteromeric complexes with Smad4, and translocate into the nucleus where they may activate transcription of various genes. Smad6 and Smad7 are inhibitory Smads, and may act as autocrine switch-off signals. In Drosophila melanogaster, Decapentaplegic (Dpp) is a homologue of mammalian BMPs. In this review, mechanism of action of Dpp will be discussed in comparison with that of BMPs.

Animals↗
PubMed1998

Identification of receptors and Smad proteins involved in activin signalling in a human epidermal keratinocyte cell line.

BACKGROUND: Activin A is a multifunctional protein, which is a member of the transforming growth factor-beta (TGF-beta) superfamily. Smad proteins have recently been shown to transduce signals for the TGF-beta superfamily of proteins, and Smad2 was implicated in activin signalling in Xenopus embryos. RESULTS: We identified the receptors and Smad proteins activated by activin A in a human epidermal keratinocyte cell line, HaCaT. The major activin receptors expressed on HaCaT cells were activin type II receptor (ActR-II) and activin type IB receptor (ActR-IB). We have also shown that in HaCaT cells, activin A induced the phosphorylation of Smad3 and, to a lesser extent, of Smad2. On the other hand, TGF-beta induced an efficient phosphorylation of both Smad2 and Smad3. Activin A preferentially induced the nuclear translocation of Smad3 in HaCaT cells, whereas TGF-beta strongly induced the nuclear translocation of Smad2, as well as other Smads. Moreover, a constitutively active form of ActR-IB efficiently stimulated the formation of a heteromeric complex between Smad3 and Smad4 in COS cells transfected with Smad cDNAs. CONCLUSIONS: These results suggest that activin A binds to a receptor complex of ActR-II and ActR-IB, and preferentially activates Smad3 in HaCaT human keratinocytes.

Activin Receptors↗
PubMed1998

Role of p300, a transcriptional coactivator, in signalling of TGF-beta.

BACKGROUND: Smad proteins are novel transcriptional regulators mediating the signalling of the transforming growth factor-beta (TGF-beta) superfamily. Coactivators such as p300/CBP promote transactivation by various transcription factors through a direct interaction with them. Adenoviral oncoprotein E1A, which binds p300, was shown to inhibit the signalling of TGF-beta. These findings raise the possibility that p300 may be involved in TGF-beta signalling. RESULTS: We investigated whether p300 is involved in transactivation by Smads. p300 enhanced the Smad-induced transactivation of p3TP-Lux, a TGF-beta responsive reporter. E1A inhibited this enhancement, and the inhibition required its ability to bind p300/CBP. p300 and Smad3, as well as Smad2, interacted in vivo in a ligand-dependent manner. The binding region in Smad3 was its C-terminal half that was previously shown to possess an intrinsic transactivation activity. The binding region in p300 was mapped to its C-terminal 678 amino acids. The minimal Smad2/3-interacting region, as well as the rest of the p300, inhibited the transactivation of p3TP-Lux in a dominant-negative fashion. CONCLUSION: p300 interacted with Smad2 and Smad3 in a ligand-dependent manner, and enhanced the transactivation by Smads. Our results present the molecular basis of the transactivation by Smad proteins.

Adenovirus E1A Proteins↗
PubMed1998

Control of rat glomerular microcirculation by juxtaglomerular adenosine A1 receptors.

The role of adenosine A1 receptors in the glomerular microcirculation and tubuloglomerular feedback (TGF) was studied in anesthetized Sprague-Dawley rats. TGF activity was assessed as the reduction in proximal tubular stop-flow pressure (SFP) on establishing orthograde perfusion of the loop of Henle with artificial tubular fluid at 40 nl/min. Administration of a selective A1 receptor antagonist, KW-3902 (0.5 microg/kg/min i.v.), increased fractional excretion of Na (FE(Na)) 4.3-fold without changing blood pressure, glomerular filtration rate, renal plasma flow, or filtration fraction. SFP in the absence of distal flow (SFP0) increased, and TGF-mediated SFP reduction was suppressed dose dependently [by 23 +/- 2% from an SFP0 of 34 +/- 1 mm Hg, by 15 +/- 4% from 36 +/- 2 mm Hg, and by 2 +/- 1% from 39 +/- 1 mm Hg during vehicle, low- and high-dose infusions (0.5 and 5.0 microg/kg/min), respectively]. Intratubular or peritubular capillary administration of 10(-4) M KW-3902 completely suppressed TGF without affecting SFP0. TGF suppression and elevation of SFP0 during systemic A1 blockade indicated vasodilation, both in the afferent arteriole and more proximal preglomerular vessels. Inhibition of tubular Na reabsorption combined with TGF suppression allowed the marked natriuresis. TGF suppression through systemic, luminal, and peritubular application of the drug suggest that juxtaglomerular apparatus A1 receptors are important in the control of glomerular microcirculation.

Animals↗
PubMed1998

Interplay of signal mediators of decapentaplegic (Dpp): molecular characterization of mothers against dpp, Medea, and daughters against dpp.

Decapentaplegic (Dpp) plays an essential role in Drosophila development, and analyses of the Dpp signaling pathway have contributed greatly to understanding of the actions of the TGF-beta superfamily. Intracellular signaling of the TGF-beta superfamily is mediated by Smad proteins, which are now grouped into three classes. Two Smads have been identified in Drosophila. Mothers against dpp (Mad) is a pathway-specific Smad, whereas Daughters against dpp (Dad) is an inhibitory Smad genetically shown to antagonize Dpp signaling. Here we report the identification of a common mediator Smad in Drosophila, which is closely related to human Smad4. Mad forms a heteromeric complex with Drosophila Smad4 (Medea) upon phosphorylation by Thick veins (Tkv), a type I receptor for Dpp. Dad stably associates with Tkv and thereby inhibits Tkv-induced Mad phosphorylation. Dad also blocks hetero-oligomerization and nuclear translocation of Mad. We also show that Mad exists as a monomer in the absence of Tkv stimulation. Tkv induces homo-oligomerization of Mad, and Dad inhibits this step. Finally, we propose a model for Dpp signaling by Drosophila Smad proteins.

Amino Acid Sequence↗
PubMed1998

Mushroom worker's lung resulting from indoor cultivation of Pleurotus osteatus.

Indoor cultivation of oyster mushroom Pleurotus osteatus lead to an outbreak of extrinsic allergic alveolitis in two workers. High titer of indirect fluorescent antibody and positive precipitins against basidiospores of P. osteatus were demonstrated in sera of the patients. Mushroom workers should protect themselves from the basidiospores, being aware of their pathogenicity.

Adult↗
PubMed1998

New diagnostic finding to assess para-Hisian pacing observed in a patient with a permanent form of junctional reciprocating tachycardia.

Para-Hisian pacing, a useful method to differentiate conduction over an accessory pathway from conduction over the AV node, is assessed essentially by comparing the timing of local atrial electrograms between His-bundle captured beats and His-bundle noncaptured beats. We describe the case of a patient with a permanent form of junctional reciprocating tachycardia, in whom an atrial double potential was recorded only during the tachycardia at the right posterior septum. During para-Hisian pacing, a morphologic change in the atrial electrogram at the posterior septum was also identified, as well as a change in the retrograde atrial sequence. Since the morphologic change of atrial electrograms during para-Hisian pacing cannot be demonstrated in a patient without an accessory pathway, this new finding could be considered a new additional diagnostic criterion suggesting the presence of an accessory pathway.

Adult↗
PubMed1998

Lyme disease Borrelia species in northeastern China resemble those isolated from far eastern Russia and Japan.

Fifty-nine Borrelia burgdorferi sensu lato culture isolates collected from northeastern China were characterized by 5S-23S rRNA intergenic spacer restriction fragment length polymorphism (RFLP) analysis and reactivity with monoclonal antibodies (MAbs). Among 59 culture isolates, 30 (50.8%) were Borrelia garinii and 17 (28.8%) were Borrelia afzelii, 2 were mixtures composed of B. garinii with RFLP pattern B and B. garinii with pattern C, and 9 were mixtures composed of B. garinii and B. afzelii. One isolate, ChY13p, produced a unique pattern and was identified as B. garinii based on analyses of 16S rRNA gene sequence, flagellin PCR-RFLP typing, and MAb reactivities. No Borrelia burgdorferi sensu stricto or Borrelia japonica isolates were detected. The results indicate that Lyme disease Borrelia species in northeastern China resemble those of Borrelia isolates from far eastern Russia and Japan.

Base Sequence↗
PubMed1998

Diffuse panbronchiolitis in rheumatoid arthritis.

The association of progressive obliterative bronchiolitis (OB) with rheumatoid arthritis (RA) is uncommon but has been reported previously. Diffuse panbronchiolitis (DPB) is a unique inflammation principally affecting the respiratory bronchioli and has been reported mainly in Japanese adults. Recently, DPB has also been noted in patients with RA in Japan. Therefore, there might be considerable overlap in clinical features between DPB and OB associated with RA in Japan. The aim of this study was to evaluate the clinicopathological characteristics of bronchiolitis in patients with RA. Three RA patients clinically diagnosed as having DPB were evaluated. All patients underwent chest radiographs, pulmonary function tests (PFT) and post mortem examination. Clinical features in all patients were a history of productive cough, exertional dyspnoea, wheezing and/or coarse crackles. Chest radiographs showed small nodular shadows up to 2 mm in diameter with bronchiolectasis throughout both lungs in all patients. The PFT revealed marked obstructive impairment in all patients. All patients died of progressive respiratory failure. Pathologically, two out of the three cases were confirmed as DPB, while the remaining one case was confirmed as OB, because the primary obstructive lesions were in the respiratory bronchioli in the former and in the membranous bronchioli and the proximal small bronchi in the latter. Thus, the clinical features of DPB and OB were strikingly similar, but the histopathological features revealed distinct differences. This study demonstrated that there was considerable overlap in clinical features between diffuse panbronchiolitis and obliterative bronchiolitis associated with rheumatoid arthritis, suggesting that diffuse panbronchiolitis might be a new manifestation of rheumatoid arthritis. The differentiation of these two disease entities is significant in making decisions on their therapeutic modality and is possible by analysing the precise histopathological findings of the lung.

Aged↗
PubMed1998

Effects of lemildipine, a new calcium channel blocker, on renal microcirculation in SHR.

The effects of lemildipine, a new dihydropyridine calcium channel blocker, on renal hemodynamics and the tubuloglomerular feedback (TGF) mechanism were examined in anesthetized 9- to 10-wk-old spontaneously hypertensive rats (SHR). Lemildipine, 3 micrograms.kg-1 i.v., did not reduce mean blood pressure (MBP) but tended to increase GFR and increased urinary excretion of sodium (UNaV). Filtration fraction (FF) and fractional excretion of sodium (FENa) remained unaltered. An additional dose of lemildipine, 9 micrograms.kg-1 i.v., reduced MBP and renal vascular resistance. Renal plasma flow tended to increase, and GFR was unchanged. FF significantly fell. UNaV and FENa remained at the control level. Micropuncture experiments revealed that the maximal reduction in proximal stop-flow pressure (SFP), an index of glomerular capillary hydrostatic pressure (Pgc), induced by perfusion of the loop of Henle was significantly reduced by high-dose treatment (8.8 +/- 1.3 vs. 13.7 +/- 1.9 mmHg in control). A high dose of lemildipine induced a rightward and slightly upward shift of the TGF curve; the steady-state tubular flow rate (V1/2) was increased, the maximal slope of the curve decreased, and SFP at V1/2 unaltered. A low dose of lemildipine did not affect TGF response. These results indicate that lemildipine attenuates the TGF response in SHR by dilating afferent arterioles and thereby corrects the left and downward shift of the TGF curve in SHR. In addition, the fall in FF indicates lemildipine-induced efferent arteriolar vasodilatation. Through balanced systemic and glomerular vasodilatation, lemildipine maintains the levels of Pgc and GFR in the face of reduced renal perfusion pressure.

Animals↗
PubMed1998

An autopsy case of peripheral neuroepithelioma in posterior mediastinum with p53 point mutation.

An 18-year old male was admitted to our hospital complaining of back pain. His chest computed tomography showed a tumor in the posterior mediastinum. Open biopsy was performed, and a diagnosis of peripheral neuroepithelioma was made. No genetic abnormalities were detected in the DNA obtained from the biopsy specimen. He received chemotherapy and radiation several times. These treatment regimens were effective, but he relapsed 14 months later and died of respiratory failure due to tumor growth. Autopsy examination revealed a large tumor which occupied almost the entire right thoracic cavity, but there was no evidence of metastasis to other organs. Chromosomal translocation t(14;17) (q24;p12.2) and point mutation of exon 5 of the p53 gene were detected.

Adolescent↗
PubMed1998

Two cases of idiopathic CD4+ T-lymphocytopenia in elderly patients.

We present 2 cases of idiopathic CD4+ T-lymphocytopenia (ICL) in elderly patients. Case 1, a 73-year-old man, with pneumonia had received several antibiotics with unsuccessful results at another hospital. On admission, his CD4+ T-lymphocyte count was 109/microl and Pneumocystis carinii was detected by bronchoalveolar lavage fluid staining. No evidence of human immunodeficiency virus (HIV) infection was found. Despite therapy, the patient died of respiratory failure. Case 2, a 72-year-old man, contracted severe pneumonia, and Hemophillus influenzae was believed to be the pathogen. On admission, his CD4+ T-lymphocyte count was 238/microl. No evidence of HIV infection was found. He received antibiotics and improved successfully. We suggest that ICL may currently be incubating in a number of elderly pneumonia patients.

Aged↗
PubMed1998

Pulmonary manifestations in cerebrotendinous xanthomatosis.

We investigated five cases with cerebrotendinous xanthomatosis (CTX) with particular reference to biochemical and pathological pulmonary disorders. To date, few reports discuss the pathophysiology of pulmonary disorders of CTX patients. This study is the first investigation of such pulmonary disorders. All 5 patients had no pulmonary symptoms and no disturbances on radiological studies and pulmonary function tests. However, in bronchoalveolar lavage (BAL) fluids, many cells with cruciform reflexes, which is characteristic of intracellular sterol accumulation, were found under phase contrast microscopy. Biochemically, cholestanol was found to be increased in the BAL fluid as well as in serum. Pathological findings of transbronchial lung biopsy (TBLB) samples disclosed foamy macrophages and small granulomas in alveolar septa. In conclusion, the lung was apparently involved in CTX, and the lesions were characterized with the accumulation of foamy and giant cells with a high concentration of cholestanol, which likely results in the formation of foreign body granulomas.

Adult↗
PubMed1998

Clinical predictors in the natural history of uterine leiomyoma: preliminary study.

This study was conducted to examine the correlation between uterine vascularity and natural history of uterine leiomyoma. Seventy women with leiomyoma participated in this study. Measurements of uterine and leiomyoma volume, as well as blood flow characteristics of the main uterine artery and leiomyoma arteries, were made every 3 months for 1 year. Leiomyoma arteries could be detected in 52 (51.5%) of 101 leiomyomas. Leiomyoma volume increased in 24 (46.2%) of 52 leiomyomas with leiomyoma artery. However, the leiomyoma volume increased in only three (6.1%) of 49 leiomyomas without leiomyoma artery. No difference was found between the pulsatility index of the leiomyoma artery in the group with increased size and in the group with stable size. This study shows the vascularity of leiomyoma to be useful as a predictor of leiomyoma growth.

Adult↗