Search PubMed⌕ Search

Biomedical subjects

K Takeda

Publications and source records attributed to K Takeda.

At least 613 records · Page 34Linked to original sources
PubMed1996

Interleukin-12 induces cytotoxic NK1+ alpha beta T cells in the lungs of euthymic and athymic mice.

We recently reported that interleukin-12 (IL-12) stimulated hepatic NK1.1 Ag+ alpha beta T cells with intermediate T-cell receptor (TCR; NK1+ TCRint cells) and enhanced their NK1 expression (NK1high TCRint), and that these cells acquire strong major histocompatibility complex (MHC) unrestricted cytotoxicity in C57BL/6 mice, both +/+ and nu/nu. In the present study, we find that although murine lung normally has few NK1+ TCRint cells, NK1high TCRint cells are induced in+/+ and nu/nu mice after systemic administration of IL-12; these cells exhibit strong MHC unrestricted cytotoxicity against NK-sensitive and -resistant targets. A small number of NK1high TCRint cells was also found in peripheral blood after increased amounts of IL-12 were administered. Cytotoxicity tests in vitro revealed that the cytotoxic activity of the lung mononuclear cells (MNC) of C57BL/6 mice induced by IL-12 was abrogated by the depletion of either NK1+ or CD3+ cells, but not of CD8+ cells, as reportedly was the case of hepatic MNC, suggesting that NK1high TCRint cells are an antimetastatic population not only in the liver but also in the lung of mice. IL-12 injection into mice markedly elevates serum interferon-gamma (IFN-gamma) levels. However, although IL-12-induced cytotoxicity of NK1high TCRint cells was significantly reduced by anti-IFN-gamma antibody injection (which decreased serum IFN-gamma to an undetectable level), the appearance of NK1high TCRint cells in the lung and liver was not so affected. These results suggest that IFN-gamma is an important mediator of the cytotoxicity of NK1high TCRint cells but is not an essential factor for induction of these cells. We also added data showing that IL-12 has a broad antimetastatic effect against various liver and lung metastatic tumours intravenously injected into several strains of mice, including NK-deficient bg/bg mice. It can be considered that, in addition to NK cells, CD8+ cytotoxic T cells and gamma delta T cells, NK1+ TCRint cells can be categorized as one of the cytotoxic effector populations. These novel type cells distinct from regular T cells may play an important role in monitoring intra- and perivascular areas.

Animals↗
PubMed1996

Novel photoactivatable agonist of the nicotinic acetylcholine receptor of potential use for exploring the functional activated state.

The nicotinic acetylcholine receptor (AChR) exhibits at least four different conformational states varying in affinity for agonists such as acetylcholine (ACh). Photoaffinity labeling has been previously used to elucidate the topography of the AChR. However, to date, the photosensitive probes used to explore the cholinergic binding site photolabeled only closed or desensitized states of the receptor. To identify the structural modifications occurring at the ACh binding site on allosteric transition associated with receptor activation, we have investigated novel photoactivatable 4-diazocyclohexa-2,5-dienone derivatives as putative cholinergic agonists. Such compounds are fairly stable in the dark and generate highly reactive carbenic species on irradiation. In binding experiments using AChRs from Torpedo marmorata, these ligands had affinities for the ACh binding site in the micromolar range and did not interact with the noncompetitive blocker site (greater than millimolar affinity). Irreversible photoinactivation of ACh binding sites was obtained with the ligand 1b (up to 42% at 500 microM) in a protectable manner. In patch-clamp studies, 1b was shown to be a functional agonist of peripheral AChR in TE 671 cells, with the interesting property of exhibiting no or very little desensitization even at high concentrations.

Acetylcholine↗
PubMed1996

The genomic structure and chromosomal localization of the mouse STAT3 gene.

A variety of cytokines induce the tyrosine phosphorylation of signal transducers and activators of transcription (STATs). Activation of the same STAT proteins by distinct cytokines and activation of different STAT proteins by each cytokine are thought to contribute to redundancy and pleiotropy of cytokine actions respectively. STAT3 is rapidly tyrosine phosphorylated in response to IL-6, ciliary neurotrophic factor, oncostatin M, leukemia inhibitory factor, IL-11, granulocyte colony stimulation factor and epidermal growth factor. In this report we have isolated and characterized the mouse genomic structure of STAT3. The mouse STAT3 gene consisted of 24 exons which spanned > 37 kb. The structure of the mouse STAT3 gene was almost identical to that of the human STAT2 gene, including the number and size of exons, indicating that the exon-intron organization had already been accomplished before these two genes duplicated, and then these genes evolved to respond to different ligands. By molecular linkage analysis with interspecific backcross mice the STAT3 gene mapped at 1.4 cM proximal to D11Mit59 on mouse chromosome 11. The promoter region contained potential regulatory elements such as GATA, NF-IL-6, PEBP2, Sp-1, AP-2 binding sites, cAMP response element, CAAT box and E-box. Transient expression of constructs harboring the 5' flanking region of the STAT3 gene fused to the luciferase gene showed that a 160 bp sequence upstream of the transcription start site conferred a basal and an IL-6-inducible promoter activity.

Animals↗
PubMed1996

Treatment of whole houses with liquid nitrogen for control of dust mites.

A large volume of liquid nitrogen, (120-150 L) was applied to the houses of 4 asthmatic patients, and the mite densities of the floor dust from these houses were monitored every 2 wk for 4 mo from July to November 1989. The 1st liquid nitrogen treatment was applied in early August and decreased the mite densities to 20-44% of the pretreatment level in all cases, but they returned to the pretreatment level 3-4 wk later (on 3 occasions). The 2nd liquid nitrogen treatment was applied in early September and decreased the mite densities to 6-27% of the pretreatment level within 3 wk in all cases. However, mite numbers again increased to the pretreatment level 4 wk after treatment. The 3rd treatment was applied in mid-October and reduced the mite densities to < 6% of the pretreatment level within 2 wk, and mite numbers remained low thereafter. The results suggested that using liquid nitrogen to freeze houses reduces mite numbers, but that mite recolonization of the houses is an important problem.

Animals↗
PubMed1996

Characterization of ficolins as novel elastin-binding proteins and molecular cloning of human ficolin-1.

A novel elastin-binding protein, EBP-37, was recently identified and purified from human plasma. Its partial amino acid sequences showed significant homology to porcine ficolins, which were originally purified from porcine uterus membranes as multimeric proteins with fibrinogen- and collagen-like domains. Here we report the presence of ficolins in an elastin-binding fraction of porcine plasma and the direct binding of recombinant porcine ficolin-alpha to elastin. In addition, a cDNA encoding a human counterpart of porcine ficolins that is composed of 319 amino acids and is different from EBP-37 was cloned and named human ficolin-1. Northern blotting of various human tissues revealed that human ficolin-1 mRNA is highly expressed in peripheral blood leukocytes. These data suggested that there are at least two kinds of ficolin-related proteins in both pig and human, and they may function as plasma proteins with elastin-binding activities.

Amino Acid Sequence↗
PubMed1996

Hypertrophic cardiomyopathy in Noonan syndrome.

Noonan syndrome, a well-known multiple congenital anomalies syndrome, is frequently accompanied by cardiovascular diseases including hypertrophic cardiomyopathy (HCM). The incidence of HCM in Noonan syndrome is approximately 20-30% and one-third of cases reveal ventricular outflow obstruction. HCM in Noonan syndrome is occasionally associated with a congenital heart defect, whereas classic HCM seldom accompanies cardiac malformations. Asymmetric septal hypertrophy and symmetric septal hypertrophy (concentric hypertrophy) can be observed both in HCM with Noonan syndrome and in classic HCM, but apical hypertrophy has not been reported in Noonan syndrome yet, although it appears in classic HCM. Congestive heart failure is the major cause of death in patients with HCM in Noonan syndrome, but cases of sudden death have also been reported. The histopathologic findings of ventricular myocardial tissue in HCM with Noonan syndrome are similar to those in classic HCM.

Adolescent↗
PubMed1996

Association of restriction fragment-length polymorphisms in the alcohol dehydrogenase 2 gene with alcoholic brain atrophy.

Alcohol abuse can induce brain atrophy, but it only occurs in some alcoholics. To investigate whether genetic polymorphism of alcohol-metabolizing enzymes [including alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH)] was related to alcoholic brain atrophy, we determined restriction fragment-length polymorphisms of the ADH2 and ALDH2 genes in 77 male alcoholics. Computed tomography was used to determine the severity of brain atrophy. Digestion with MaeIII and MboII after polymerase chain reaction amplification showed that the ADH2(1) gene frequency was significantly higher in patients with brain atrophy than in those without brain atrophy (chi 2 = 9.274, p < 0.01), whereas no significant association was observed between brain atrophy and the ALDH2 gene Multivariate analysis (including age, total alcohol intake, liver cirrhosis, and ADH2 genotype) showed that the ADH2(1)/ADH2(1) genotype was associated with alcoholic brain atrophy. These findings suggest that the ADH2(1) allele may be associated with alcoholic brain atrophy.

Adult↗
PubMed1996

Expression of mRNA encoding intestinal type alkaline phosphatase in rat liver and its increase by fat-feeding.

The presence of types of alkaline phosphatase (ALP) other than the tissue non-specific type enzyme in rat liver and its increase by fat feeding are known. In order to examine expression of intestinal type ALP in liver, specific oligonucleotide primers corresponding to two types of mRNAs of rat intestinal ALP (RTIN-1 and -2) were designed and amplified by means of the reverse transcriptase-polymerase chain reaction (RT-PCR). It was found that RTIN-1 mRNA was expressed only in the intestine but not in the liver, while RTIN-2 mRNA was expressed both in the intestine and in the liver. By fat feeding, expression of RTIN-1 mRNA increased in the intestine and that of RTIN-2 mRNA increased both in the intestine and in the liver. Thus, it was concluded that rat liver expressed one of the intestinal type ALP (RTIN-2) which was enhanced by fat feeding.

Alkaline Phosphatase↗
PubMed1996

[Isolation of Vibrio cholerae in imported frozen seafood and their cholera-enterotoxin production].

A survey study for Vibrio cholerae in imported seafood was conducted during January 1991 to December 1994. A total of 7,439 specimens (approximately 20% of all imported food) were randomly picked up and examined for contamination of V. cholerae. Among these, V. cholerae O1 were isolated from 9 specimens, but they were all cholerae enterotoxin (CT)-negative. In terms of V. cholerae non-O1, a total of 2,803 specimens (37.4%) were contaminated with this vibrio. Shrimp, especially the ones still in their shells and imported from Asian countries such as India and Indonesia, were highly contaminated with V. cholerae. Although no strains of V. cholerae O1 isolated in this study produced CT, 2 strains of V. cholerae non-O1 were proved to be CT-producers. Taking together the high contamination of V. cholerae in imported seafood and a part of those strains producing CT, we believe that careful survey for the possible contamination of V. choleare in imported seafood is necessary.

Cholera Toxin↗
PubMed1996

Thyroxine-binding globulin: organization of the gene and variants.

Thyroxine-binding globulin (TBG), the principal thyroid hormone transport protein in human serum, is synthesized by the liver and secreted into the bloodstream as a 54-kD acidic glycoprotein made up of a single polypeptide chain of 395 amino acids and four heterosaccharide units. The carbohydrate chains are important for the correct posttranslational folding, secretion and degradation of the molecule but are not required for hormone binding. TBG, encoded by a single gene copy located on Xq22, consists of five exons spanning 5.5 kbp. An upstream sequence of 218 nucleotides containing a hepatocyte nuclear factor 1 binding motif imparts to the gene a strong liver-specific transcriptional activity. Inherited TBG defects produce three phenotypes based on the level of TBG in serum of affected hemizygotes: complete TBG deficiency (TBG-CD), partial TBG deficiency (TBG-PD) and TBG excess (TBG-E). The molecular basis of the TBG defect has been identified in 12 of 16 known TBG variants. TBG-CD is caused by either premature termination of translation or an amino acid substitution resulting in failure of secretion. Point mutations resulting in single amino acid substitutions are responsible for the alteration of the properties and/or concentration of TBG-PD variants. Gene duplication and triplication has been recently identified in subjects with TBG-E.

Base Sequence↗
PubMed1996

Analysis of the derangement of the pancreatic microcirculation in a rat caerulein pancreatitis model using an intravital microscope system.

In order to clarify the derangement of the pancreatic microcirculation in acute pancreatitis, the pancreatic microcirculation in caerulein pancreatitis was monitored intravitally and the roles of bradykinin and nitric oxide were examined using bradkykinin B2 receptor antagonist, HOE140. Under an intravital microscope, the pancreatic microcirculation was observed 2 or 6 hr after the induction of acute pancreatitis. HOE140 was administered 30 min before the induction of acute pancreatitis. The videoimages were taken into the computer, and the value of grayscale was measured with imaging software to quantify the degree of extravasation. Extravasation in the postcapillary venules was remarkable and the velocity in pancreatic terminal arterioles decreased significantly. However, the adherence of leukocytes was not observed until 6 hr after the induction. Both the extension of extravasation and the decrease of velocity were prevented by HOE140. The levels of nitric oxides in the pancreatic tissue declined and this decline was not influenced by HOE140. Bradykinin participates mainly in the regulation of vascular permeability in the early stage of caerulein pancreatitis. Further, the impairment of pancreatic microcirculation may play a key role in the onset and development of acute pancreatitis.

Acute Disease↗
PubMed1996

A mRNA for membrane form of guanylyl cyclase is expressed exclusively in the testis of the sea urchin Hemicentrotus pulcherrimus.

A cDNA clone encoding the membrane form of guanylyl cyclase was isolated from a Hemicentrotus pulcherrimus testis cDNA library and its nucleotide sequence was determined. The cDNA was 4123 bp long and an open reading frame predicted a protein of 1125 amino acids including an apparent signal peptide of 21 residues; a single transmembrane domain of 25 amino acids which divides the mature protein into an amino-terminal, extracellular domain of 485 amino acids and a carboxyl-terminal, intracellular domain of 594 amino acids. Three potential N-linked glycosylation sites were present in the extracellular domain. Northern blot analysis of poly(A)+RNA from testes, ovaries, eggs and embryos at various developmental stages showed that the cDNA encoding guanylyl cyclase hybridized to a mRNA of 4.4 kb from the testes. We developed a large scale purification method of the phosphorylated (131 kDa) and dephosphorylated (128 kDa) forms of the membrane-bound guanylyl cyclase from H. pulcherrimus spermatozoa. The purified 131 kDa and 128 kDa forms of the guanylyl cyclase contained 26.0 +/- 1.3 and 4.3 +/- 0.7 moles of phosphate per mol protein (mean +/- S.D.; n = 6), respectively. The amino-terminal amino acids of both the 131 kDa and 128 kDa forms of the guanylyl cyclase could not be detected, suggesting that they were blocked.

Amino Acid Sequence↗
PubMed1996

Picrotoxin potentiates contraction while inhibiting Ca current but increasing birefringence signal in frog skeletal muscle fibers.

In single frog skeletal muscle fibers, picrotoxin (5 mM) potentiated the voltage-dependent component of contractions in response to 2-s depolarizing pulses while greatly inhibiting the simultaneously recorded tubular Ca current in a normal-Ca, Na- and CI-deficient solution, provided the contractions were generated at long time intervals (2 min). In normal Ringer's solution, picrotoxin reversibly increased the amplitude of the early large birefringence signal and the amplitude and duration of the simultaneously recorded twitch tension, suggesting that the drug may increase, directly or indirectly, the release of Ca from the SR.

Animals↗
PubMed1996

Technical note: use of a PCR-single strand conformation polymorphism (PCR-SSCP) for detection of a point mutation in the swine ryanodine receptor (RYR1) gene.

We used the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis for screening the point mutation (C1843 to T) in the porcine ryanodine receptor (RYR1) gene. The PCR products (659 bp) were heat-denatured and separated by polyacrylamide gel electrophoresis. On silver-stained gels, the point mutation within the RYR1 gene could be detected clearly by mobility shifts. The best conditions for detecting the point mutation were by using a 5% polyacrylamide gel without glycerol and loading at 3 degrees C. The RYR1 genotypes diagnosed by PCR-SSCP were identical to the genotypes diagnosed by restriction enzyme fragment length polymorphism in all cases examined (n = 606).

Animals↗
PubMed1996

Cold activation of complement for monitoring the response to interferon in patients with chronic hepatitis C.

OBJECTIVES: Because of its specific association with hepatitis C virus (HCV) infection, the cold activation of complement is an easy and inexpensive indicator of HCV viremia. It was evaluated for eligibility as a marker of response to interferon in patients with hepatitis C. METHODS: The cold activation of complement was determined by the loss or decrease of hemolytic activity with the microtitration method in sera that had been stored at 4 degrees C overnight. RESULTS: We observed the loss of hemolytic activity by the cold activation of complement in 236 (72%) and a decrease in 56 (17%) of 327 sera from patients with HCV-associated chronic liver disease, which was much more (p < 0.001) that in 1 (1%) and 13 (14%), respectively, of 49 sera from patients with chronic liver disease associated with hepatitis B virus infection. Interferon-alpha (total dose 516 x 10(6) units) or interferon-alpha 2b (774 x 10(6) units) was given to 67 patients with chronic hepatitis C, of whom 56 had the cold activation of complement. The response to interferon was evaluated by the clearance of serum HCV RNA at 6 months after the completion of therapy. The cold activation of complement disappeared in 18 patients, of whom 15 (86%) responded. It persisted or fluctuated in the remaining 38 patients, only six (16%) of whom responded to interferon (p < 0.001). The cold activation of complement once disappeared at the completion of interferon and then reappeared in patients who relapsed after completing interferon therapy. CONCLUSIONS: These results indicate that the cold activation of complement may be associated with the presence of HCV in blood and a lower rate of durable response after completion of interferon therapy.

Adult↗
PubMed1996

[Presurgical evaluation of cerebral perfusion reserve in patients for cardiovascular surgery using 99mTc-ECD SPECT with diamox enhancement].

Cerebrovascular stroke is one of the major complications in cardiovascular surgery with cardiopulmonary bypass. The purpose of this study was to evaluate the usefulness of preoperative 99mTc-ethyl cysteinate dimer (ECD) SPECT and acetazolamide (diamox) enhancement to predict neurological complications in cardiovascular surgery. Eighteen patients with coronary disease, valvular disease or aortic aneurysm were studied before the operations. Regional cerebral blood flow and perfusion reserve were evaluated using ECD SPECT before and after the intravenous administration of diamox (1 g). Three cases with moderate to severe baseline abnormalities and poor perfusion reserve had cerebral infarction postoperatively. Twelve cases with good to fair perfusion reserve had no neurological complication. Three cases having poor perfusion reserve had the operations with more intensive brain protection, in which higher perfusion pressure to the brain was maintained during cardiopulmonary bypass, and no neurological complication was observed. In conclusion, patients who have moderately or markedly abnormal baseline flow with poor perfusion reserve may have some risk of neurological complications in cardiovascular surgery. ECD SPECT with diamox enhancement may give information useful for selection of operation procedures.

Acetazolamide↗