Search PubMed⌕ Search

Biomedical subjects

T Imamura

Publications and source records attributed to T Imamura.

At least 307 records · Page 17Linked to original sources
PubMed1996

Plasma adrenomedullin concentration in patients with heart failure.

We measured plasma concentrations of adrenomedullin (AM), a novel bioactive peptide with potent vasodilator activity, in 21 patients with chronic congestive heart failure due to various heart diseases and compared them to levels in age- and sex-matched healthy subjects to examine the pathophysiological role of plasma AM in heart failure. In addition, the relationship between plasma AM and other hormones known to control the cardiovascular system was examined in these patients. The plasma AM level in the patients with heart failure was significantly (P < 0.01) higher than that in the control subjects (mean +/- SEM, 2.94 +/- 0.15 fmol/mL; n = 16), with a significantly (P < 0.05) higher concentration in patients in class III or IV (11.82 +/- 1.81 fmol/mL; n = 5) of the New York Heart Association functional classification than in those in class I or II (8.74 +/- 0.44 fmol/mL; n = 16). There were no significant correlations between plasma AM and catecholamine levels, whereas the plasma AM level was significantly correlated with the concentrations of plasma atrial natriuretic peptide (r = 0.58; P < 0.01), brain natriuretic peptide (r = 0.47; P < 0.05), and PRA (r = 0.77; P < 0.01) in the patients. Thus, the plasma AM concentration increased in proportion to the severity of heart failure along with the hormones known to modulate the development of congestive heart failure. The present findings suggest a possible role for AM as a circulating hormone participating in the defense mechanism against further deterioration of congestive heart failure in patients with heart disease.

Adrenomedullin↗
PubMed1996

Medial medullary infarction: analyses of eleven patients.

Of 2,130 consecutive patients admitted to two hospitals with acute brain infarction, we examined 11 patients (0.52%) with medial medullary infarction. The infarcts documented by MRI were unilateral in 9 patients and bilateral in 2 patients, and located in the anteromedial arterial territory of the upper or middle part of the medulla. Atherosclerosis of the vertebral arteries was the predominant vascular pathology. The vertebral artery was occluded at its terminal portion in 7 patients. Nine patients had hypertension, and 8 of these had additional risk factors. Male gender (10 patients) and smoking habits (7 patients) were more prevalent compared with patients with pontine infarction. One patient had a medial medullary infarction attributed to dissection of the vertebral arteries following blunt head injury. Limb weakness was the major symptom in all patients, and gaze-evoked nystagmus was also frequent (6 patients). Tongue weakness ipsilateral to the infarct, the classic sign of medial medullary syndrome, was evident in only 3 patients. The outcome was usually excellent.

Adult↗
PubMed1996

Induction of vascular permeability enhancement by human tryptase: dependence on activation of prekallikrein and direct release of bradykinin from kininogens.

Tryptase is a trypsin-type serine protease that is released from mast cells. Bradykinin (BK) is released directly from kininogens or through activation of either Hageman factor or subsequent plasma prekallikrein. Its nasal administration or inhalation induces allergy-like symptoms. Although elevated levels of tryptase and BK in allergic fluids have been detected, the role of this proteinase and the mechanism of BK production at allergic reaction sites are still unknown. To investigate the pathologic functions of tryptase, the enzyme, purified from human lung, was incubated with normal human plasma, deficient plasmas, kininogens, or prekallikrein. High molecular weight kininogen was then added, and the mixtures were examined for vascular permeability enhancement (VPE) activity, a representative function of bradykinin, using guinea pig skin. Tryptase-treated plasma induced VPE in a dose-dependent manner; activity was lost in the absence of a kininase inhibitor but not an antihistamine drug. Tryptase produced VPE activity from normal or Hageman factor-deficient plasma, but only 30% of this activity was produced from prekallikrein-deficient plasma. Significantly, no activity was obtained from kininogen-deficient plasma. Deficient plasma that were reconstituted with each missing factor resulted in VPE-inducing capacity by tryptase, equivalent to that found with normal plasma. Incubation of tryptase with high or low molecular weight kininogen induced VPE activity in a dose- and incubation time-dependent manner. Prekallikrein incubated with tryptase also generated a soybean trypsin inhibitor-sensitive VPE-inducing activity from high molecular weight kininogen. The loss of tryptase VPE-producing activity as a function of incubation time was found to be a result of spontaneous inactivation of the enzyme and not of the degradation of high molecular weight kininogen by the enzyme. We conclude that tryptase induces VPE by releasing BK, primarily through prekallikrein activation, but also through direct release from kininogens. This indicates that this mast cell-derived proteinase contributes to kinin production in allergic diseases.

Animals↗
PubMed1996

Brain death diagnosed by forensic analysis of drug distribution in human tissues-II--Distribution of caffeine in brain dead patients.

Caffeine concentrations in human tissues of 6 brain death cases as well as 5 non-brain death cases were examined in order to assess the possibility of diagnosing brain death based on an analysis of this compound. Concentrations of caffeine in human tissues were determined using gas chromatography/mass spectrometry. The tissue-to-blood concentration ratios were used to evaluate the distribution pattern in each case. In non-brain death cases, the ratios in all examined tissues were similar, and the values were close to 1 in all tissues except adipose, of which the value was near 0.3. In brain death cases, the ratios in all tissues except brain and adipose were similar to those in non-brain death cases. The ratios in the brain were higher than those of non-brain death cases, in 5 brain death cases, and lower in 1 brain death case to whom blood transfusion was done in a hospital. The ratios in the adipose were slightly higher in brain death cases than those in non-brain death cases. The discorded distribution of caffeine in brain death cases was presumably related to cessation of cerebral blood circulation at the time of brain death. Therefore, comparing caffeine concentrations in the brain with those in the other tissues can be useful for a forensic diagnosis of brain death.

Adult↗
PubMed1996

Screening of antipsychotic drugs by wide-bore capillary gas chromatography with nitrogen phosphorus detection--detection levels in plasma.

The detection levels of 12 antipsychotic drugs as ascertained from drug screening were examined in order to use the screening results effectively for treatment of patients or medico-legal examinations in cases of poisoning. Wide-bore capillary gas chromatography with nitrogen phosphorus detection was used for the analysis. The detection limits of drugs in plasma using 3 extraction procedures, single-solvent, 3-step solvent and solid-phase extractions were 50-100 ng/ml, 10-200 ng/ml and 5-50 ng/ml, respectively. The detection limits were compared with blood levels previously reported in the literature. Only 4 drugs were detected at the therapeutic level, thioridazine, floropipamide, sultopride and oxypertine using the single-solvent extraction procedure. Using the 3-step solvent extraction procedure, chlorpromazine, levomepromazine and zotepine in addition to the above 4 drugs were detected. Using the solid-phase extraction procedure, 8 of 12 drugs were able to be detected at the therapeutic level, with the exception of perphenazine, haloperidol, bromperidol and nemonapride. These data were proved to be useful for a rapid forensic diagnosis.

Antipsychotic Agents↗
PubMed1996

[Human hemoglobin structure and respiratory transport].

Hemoglobin carries oxygen from the lungs to the tissues and helps to transport carbon dioxide back to the lungs. It fulfills this dual role by clicking back and forth between two alternative structures, designated T for tense and R for relaxed, which are defined by the theory of allostery. Like all proteins, it is made up of small molecules called amino acids. A hemoglobin molecule is made up of four polypeptide chains, two alpha chains of 141 amino acid residues each and two beta chains of 146 amino acid residues each. In the complete molecule, four subunits are closely joined, as in a three-dimensional jigsaw puzzle, to form a tetramer. In the T structure, the subunits of the molecule are clamped by salt bridges and hydrogen bonds against the pressure of springs and their narrow pockets impede the entry of oxygen. In the R structure, all the clamps have sprung open and the heme pockets are open wide enough to admit oxygen easily. Uptake of oxygen by the T structure would strain the clamps until they all burst open in concert and allow the molecule to relax to the R structure. Loss of oxygen will narrow the heme pockets and allow the T structure to re-form.

Allosteric Regulation↗
PubMed1996

[The efficacy of short-term hospitalizations in family care for patients with Pick's disease].

The purpose of this study is to investigate the efficacy of short-term hospitalization on family care for patients with Pick's disease (PD). Subjects were 12 patients with clinical diagnosis of PD based on clinical and neuroimaging criteria. They were selected from 483 patients with cognitive disorders who had been admitted to our hospital from January, 1994 to September, 1995. During 1.5-month hospital stay, we gave therapeutic intervention to the patients and their care-givers. Ten patients completed the planned term (1.5 months) of hospitalization. After the discharge, 9 patients continued to visit regularly the outpatient clinic. One patient discontinued to visit us and 2 patients were admitted to psychiatric hospitals because of stereotypic thefts or disinhibitional behavior. The benefits of short-term hospitalization in family care for PD patients were; i) close observation and analysis of patients' behavior under hospitalization offering strategies of behavioral therapy; ii) adequate instruction to the care-givers for their preparation for patients' malbehavior decreasing their burden; and iii) patients' familiarization to the hospital helping for patients to maintain regular visit to the hospital and to utilize other medical and social resources.

Adult↗
PubMed1995

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↗
PubMed1995

Desquamative interstitial pneumonia in sibs.

We report on 2 sibs with desquamative interstitial pneumonia. The female died at age 1 7/12 years despite use of prednisolone and methylprednisolone, while the male, now age 3 years. is alive with oxygen support. The occurrence of desquamative interstitial pneumonia in sibs born to normal parents suggests that in some cases the disease is an autosomal-recessive trait.

Female↗
PubMed1995

Cloning and characterization of a human type II receptor for bone morphogenetic proteins.

Bone morphogenetic proteins (BMPs) are members of the transforming growth factor beta superfamily. Several members of this family have been shown to transduce their signals through binding to type I and type II serine-(threonine) kinase receptors. Here we report the cDNA cloning and characterization of a human type II receptor for BMPs (BMPR-II), which is distantly related to DAF-4, a BMP type II receptor from Caenorhabditis elegans. In transfected COS-1 cells, osteogenic protein (OP)-1/BMP-7, and less efficiently BMP-4, bound to BMPR-II. BMPR-II bound ligands only weakly alone, but the binding was facilitated by the presence of previously identified type I receptors for BMPs. Binding of OP-1/BMP-7 to BMPR-II was also observed in nontransfected cell lines. Moreover, a transcriptional activation signal was transduced by BMPR-II in the presence of type I receptors after stimulation by OP-1/BMP-7.

Amino Acid Sequence↗
PubMed1995

Identification of the domain within fibroblast growth factor-1 responsible for heparin-dependence.

While the prototype members of the fibroblast growth factor (FGF) family, FGF-1 and FGF-2 are structurally related, the structural differences between these polypeptides predict that they will ultimately exhibit different biological roles. Indeed, a significant difference between these proteins is the dependence of FGF-1 on heparin for the generation of maximal mitogenic activity. In order to gain structural insight into the issue of FGF-1 heparin-dependence, a synthetic gene encoding FGF-2 was constructed with oligonucleotides in a four-cassette format similar to a synthetic gene previously constructed for FGF-1 (Forough et al. 1992, Biochem. Biophys. Acta 1090 293-298). This strategy permitted the molecular shuffling of corresponding cassette(s) between FGF-1 and FGF-2 to yield FGF-1:FGF-2 chimeras. Three amino acid changes (Lys86-->Glu, Tyr120-->His, and Thr121-->Ala) were introduced into the synthetic FGF-2 gene by the cassette format to generate convenient FGF-1 restriction sites, but these alterations did not significantly affect the mitogenic activity or the heparin-binding affinity of the recombinant FGF-2 protein when compared with native FGF-2. Among the various FGF-1:FGF-2 chimeric constructs, one designated FGF-C(1(1/2)1 1), which represents FGF-1 containing FGF-2 amino acid residues 65 to 81, displayed FGF-1-like heparin-binding affinity but it did not require the addition of exogenous heparin to manifest its mitogenic activity. These data suggest that the sequence within residues 65 and 81 from FGF-2 significantly contributes to the heparin-dependent character of FGF-1.

Amino Acid Sequence↗
PubMed1995

An extracellular domain of the beta subunit is essential for processing, transport and kinase activity of insulin receptor.

The extracellular portion of the insulin receptor (IR) beta-subunit has four cysteine and four asparagine residues which are potentially involved in disulphide bond formation between the alpha- and beta-subunits and N-linked glycosylation respectively. However, the function of this portion is not fully understood. In order to investigate the role of the extracellular domain of beta-subunit, we created a deletion mutant of IR cDNA which lacked 47 amino acid residues encoded by 141 bp corresponding to exon 13 of the IR gene. Insulin binding and surface labelling of COS 7 cells transiently expressing the mutant insulin receptors (IR delta Ex13) showed that the mutated receptors were not expressed on the cell surface. However, immunoblot analysis showed that uncleaved form (190 kDa) of the mutant receptors were intracellularly expressed. Deglycosylation with endoglycosidase H showed that the mutant receptors had mainly high-mannose oligosaccharide chains. The mutant IRs bound with high affinity to lentil lectin but with low affinity to wheat germ agglutinin. Therefore, it is suggested that misfolding of the mutant receptors inhibits transport to the Golgi apparatus where processing of oligosaccharide chains, as well as proteolytic cleavage into subunits, takes place. The binding affinity of the mutant receptors for insulin was 50% of normal. Furthermore, insulin-stimulated autophosphorylation of IR delta Ex13 was markedly impaired. These data provide the evidence for a critical role of the extracellular domain of IR beta-subunit for processing and transport as well as the intramolecular signal transduction to activate IR tyrosine kinase.

Base Sequence↗
PubMed1995

Enhanced expression of type I receptors for bone morphogenetic proteins during bone formation.

Type I receptors for bone morphogenetic proteins (BMPs), i.e., BMPR-IA and BMPR-IB, are transmembrane serine/threonine kinases, that bind osteogenic protein-1 (OP-1, also termed BMP-7) and BMP-4. Using antibodies specific to BMPR-IA and -IB, we have studied the expression of BMP type I receptors in the bone formation process during embryonic development and fracture healing. In the mouse embryo, both BMPR-IA and -IB were expressed in condensing mesenchymal cells at 13.5 days post coitum (p.c.). At 15.5 days p.c., expression of BMPR-IB, but not of BMPR-IA, was observed in the cells in perichondrium of developing cartilage. At 17.5 and 19.5 days p.c., expression of both receptors was observed in chondrocytes and in osteoblasts. In normal rat adult bone, expression of BMPR-IA, but not of BMPR-IB, was observed in osteoblasts in the periosteum. Three days after the femoral fracture, expression of BMPR-IA and -IB was up-regulated in cells at the proliferating osteogenic layer of the periosteum. On day 7, both receptors were found in fibroblast-like spindle cells and chondrocytes in the endochondral ossification sites, and osteoblasts in the newly formed trabecular bone. Expression of BMPR-IA was higher than that BMPR-IB in osteogenic layer on day 3 and in osteoblasts in the trabecular bone on day 7. On day 14, expression of BMP type I receptors was observed at similar sites, albeit with lower expression levels than were observed on day 7. The present data suggest that expression of BMP type I receptors is up-regulated during bone formation, and that they may play important roles in bone morphogenesis.

Animals↗
PubMed1995

Usefulness of platelet-derived growth factor as a prognostic factor in pulmonary adenocarcinoma.

Platelet-derived growth factor (PDGF) in the resected pulmonary adenocarcinoma tissue of 88 patients was detected immunohistochemically by the avidin-biotin-peroxidase technique to determine whether or not it is a prognostic parameter. The 88 patients were divided into PDGF (-) and PDGF (+) groups according to the stainability of the factor. The PDGF (-) group included 39 patients and the PDGF (+) group 49. The 5-year survival rate was 53% for the PDGF (-) group and 17% for the PDGF (+) group (P < 0.01). These findings indicate that the stainability of PDGF can be a prognostic parameter for pulmonary adenocarcinoma.

Adenocarcinoma↗
PubMed1995

Transcriptional repression of smooth-muscle alpha-actin gene associated with human papillomavirus type 16 E7 expression.

To explore the role of the E7 viral oncogene from human papillomavirus type 16 (HPV 16) in the regulation of cytoskeletal organization, we investigated alterations in particular cytoskeletal components in rat embryonal fibroblasts and three transformants of rat embryonal fibroblast cells produced by transfections with HPV16 E7 alone (TF1), HPV16 E7 plus adenovirus type 5 E1B (TF3), and HPV16 E7 plus activated Ha-ras (TF4). Marked reductions in smooth-muscle (SM) alpha-actin content and disrupted organization of stress fibers detected by anti-SM alpha-actin antibody were evident in all the transformants. These cytoskeletal manifestations were associated with a significant reduction in the mRNAs in these cells. Transcriptional repression by the E7 gene was observed after transient transfection of a chloramphenicol acetyltransferase reporter gene with SM alpha-actin gene promoter. Nucleotides -123 to -39 of the SM alpha-actin gene promoter were required for the HPV16 E7 transcriptional repression as shown by the chloramphenicol acetyltransferase assay. The downregulation of this actin isoform mediated by the E7 oncoprotein may play an important role in cell transformation by HPV16.

3T3 Cells↗
PubMed1995

A synthetic peptide corresponding to a critical intracellular signaling region of the human IL-4 receptor inhibits IL-4-induced proliferation.

We have previously identified a critical region for growth signal transduction in the cytoplasmic domain of the human IL-4 receptor (hIL-4R). Since the entire cytoplasmic domain of this receptor lacks known catalytic activities such as the tyrosine kinase domain, it is likely that the IL-4R associates with other signal-transducing molecules through this critical cytoplasmic region. We test here whether a synthetic peptide corresponding to this critical cytoplasmic region, designated SP-1, interferes with IL-4-induced proliferation by competing with the IL-4R for binding to intracellular signal-transducing molecules. Our data indicated that 100 micrograms/ml SP-1 peptide completely inhibits human IL-4 (hIL-4)-induced proliferation of Ba/F3 transfectants expressing the full-length hIL-4R (hIL-4R-Ba/F3 transfectants). In contrast, a wide concentration range of an unrelated synthetic peptide, designated SP-2, did not affect hIL-4-induced proliferation of hIL-4R-Ba/F3 transfectants. This difference between SP-1 and SP-2 peptides was not due to their differential uptake by cell, since approximately 100 times more SP-2 peptide could be found in cytoplasmic extracts than SP-1 peptide in experiments using radiolabeled peptides. The specificity of SP-1-mediated inhibition of IL-4-induced proliferation was supported by the fact that the SP-1 peptide had no effect on IL-3-induced proliferation of the same hIL-4-Ba/F3 transfectants. In addition, the SP-1 peptide did not affect either IL-2-induced proliferation of Ba/F3 transfectants expressing the human IL-2 receptor beta chain (hIL-2R beta) or hIL-4-induced proliferation of Ba/F3 transfectants expressing a chimeric receptor consisting of the hIL-4R extracellular domain and the hIL-2R beta cytoplasmic domain. SP-1 was unable to inhibit IL-4-induced proliferation of other IL-4-responsive cell lines such as human erythroleukemic cell line TF-1 and mouse T cell lines HT2 and CTLL-2. In addition, SP-1 caused only a 50% inhibition of Ba/F3 cell proliferation induced by mouse IL-4. The failure of SP-1 to inhibit IL-4-induced proliferation in these various cell lines while producing excellent inhibition of hIL-4-induced proliferation of hIL-4R-Ba/F3 transfectants appeared to be related to the number of IL-4Rs expressed on each cell type.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed1995

Thrombin receptor-mediated synovial proliferation in patients with rheumatoid arthritis.

Synovial cell proliferation is one of the pathological bases of rheumatoid arthritis (RA). Several cytokines including IL-1 and IL-6 and growth factors have been shown to be involved in the synovial cell proliferation in RA. Thrombin is a multifunctional protease and acts as a mitogen for several cell types through its specific receptor. To assess whether thrombin is involved in overproliferation of rheumatoid synovial cells, we measured the concentration of thrombin-anti-thrombin III (ATIII) complex (TAT) in synovial fluid obtained from patients with RA or osteoarthritis (OA). We also examined the effect of thrombin or thrombin receptor agonist peptide (TRAP) on cell growth of synovial cell clones (SCCs) established from an RA patient. The concentrations of TAT in the synovial fluid from patients with RA were significantly higher than in those with OA. Moreover, both thrombin and TRAP enhanced proliferation of synovial cells in vitro. We also characterized the expression of thrombin receptor mRNA by reverse transcription-PCR. The expression of mRNA for thrombin receptor was up-regulated by thrombin or TRAP stimulation. Thrombin receptor antigen was also detected on both SCCs and synovial tissue from RA patients by immunostaining using a monoclonal antibody against thrombin receptor. These findings indicate that thrombin may act as a mitogen for synovial cells through thrombin receptor and may play some role in synovial overproliferation and remodeling in RA.

Adult↗