Biomedical subjects

K Sakamoto

Publications and source records attributed to K Sakamoto.

At least 343 records · Page 19Linked to original sources

PubMed1997

[An autopsy case of severe tuberculosis associated with anal fistula and intestinal perforation].

A 55 year-old man was admitted to the department of the gastroenterology of the hospital because of severe weakness and appetite loss for the past one month. In the last two months, he has been suffering from recurrent fistula of the anus. He left his symptoms without therapy. A gastric ulcer was found out with gastric endoscopy. At the same time, chest X-ray film showed bilateral abnormal shadows, which were suspected of severe pulmonary tuberculosis by a chest physician. After the admission, the patient immediately developed respiratory failure. Both sputa and discharge from anal fistula were positive for acid fast bacillus. Despite of anti-tuberculosis therapy and mechanical ventilation, he died of respiratory failure. At the autopsy, severe pulmonary tuberculosis, tuberculous fistula of the anus, intestinal tuberculosis with perforation, miliary tuberculosis and peptic ulcer of the stomach were defined. We suspected that the extensive disease caused by hematogeneous spread and the late diagnosis of tuberculosis was owing to patient's delay.

Fatal Outcome↗

PubMed1997

Neutrophil elastase inhibitor (ONO-5046.Na) suppresses the proliferation, motility and chemotaxis of a pancreatic carcinoma cell line, Capan-1.

ONO-5046. Na is a specific neutrophil elastase inhibitor. We investigated the in vitro effect of ONO-5046. Na on the proliferation, motility and chemotaxis of a pancreatic carcinoma cell line (Capan-1, well differentiated adenocarcinoma). ONO-5046. Na significantly suppressed the proliferation, motility and chemotaxis at a concentration of more than 100, 10 and 1 microgram/ml of ONO-5040. Na, respectively (p < 0.005, p < 0.05 and p < 0.05, respectively). These results indicate that ONO-5046. Na may have a role in preventing the progression and metastasis of pancreatic carcinoma cells, suggesting that ONO-5046. Na may serve as an anti-cancer agent.

Adenocarcinoma↗

PubMed1997

[Bufferin-induced lung injury manifesting as acute eosinophilic pneumonia].

A 26-year-old woman was admitted to our hospital because of dyspnea and fever one day after taking medicines for the common cold. A chest roentgenogram and a computed tomogram revealed diffuse patchy infiltrates in both lung fields. Examination of a specimen obtained by transbronchial lung biopsy showed thickening of alveolar walls and infiltration of eosinophils. Bronchoalveolar lavage fluid had many eosinophils. DLST was positive for Bufferin, which the patient took one day before the dyspnea and fever began. We believe that this patient's pulmonary disease was caused by Bufferin. We should realize that this widely used analgesic can cause acute eosinophilic lung disease. The patient was not given corticosteroids, and her condition improved soon after she stopped taking Bufferin.

Adult↗

PubMed1997

Relationship between mortality rate of stomach cancer and cerebrovascular disease and concentrations of magnesium and calcium in well water in Hyogo prefecture.

The concentration of Mg, Ca and total hardness of well and tap water were examined in 98 towns and cities in Hyogo prefecture. The annual mortality rates of stomach cancer and CVD in these areas during 1975-1979 were analyzed by the concentration of Mg and Ca in well water. The mortality rate of stomach cancer was correlated significantly positively to Mg2+/Ca2+ ratio of well water, and a similar tendency was shown in tap water. A covariance analysis indicated Mg2+ to be correlated significantly to the mortality rate of stomach cancer. Thus, it is suggested that the relatively high concentration of Mg2+ compared to Ca2+ in drinking water might be one of the causes of stomach cancer in Japanese. But the concentration of Ca2+ was correlated significantly negatively to the mortality rate of CVD.

Calcium↗

PubMed1997

[A case of humidifier lung characterized by histopathologic feature].

A 61-year-old man was discharged from our hospital after recovering from bilateral fractures in the neck of each femur. However, a productive cough, dyspnea, and a high grade fever occurred eight hours after returning home. He was thus admitted once more. At rehospitalization, there was radiographic evidence of bilateral infiltrates and hypoxemia. Hypersensitivity pneumonitis was strongly suggested by radiographic evidence, by the fact that no new drugs had been administered, and by a positive result after an environmental provocation test. A diagnosis of humidifier lung was confirmed by a positive precipitins test for humidifier water. Several microorganisms were isolated from humidifier water, and precipitins tests for the isolated microorganisms were mostly positive. Microscopic examination revealed focal alveolitis, bronchiolitis, and perivasculitis. Perivascular leucocytic infiltrations around venules suggested that inhaled antigens might have also caused humidifier lung via a vascular route. Humidifier lung may be due in part to soluble factors, such as endotoxin, present in humidifier water.

Alveolitis, Extrinsic Allergic↗

PubMed1997

Interaction of nitrosyl Fe(II) complex of bleomycin with DNA.

ESR spectra of Fe(III)BLM and NO-Fe(II)BLM on highly oriented DNA-fibers indicated that not only the iron binding domain of the BLM but also the orientation of NO bond axis is fixed with respect to the DNA-double helical axis at room temperature.

Animals↗

PubMed1997

Study on site specific cleavage of RNA.

The precursor of an RNA molecule from bacteriophage T4 infected Escherichia coli cell (p2Sp1 RNA) has the ability to cleave itself. It has been found that the site specific RNA cleavage reaction occurred at the pyridine-adenosine sequence in the presence of a monovalent cation and a non-ionic detergent. In order to investigate the mechanism of this cleavage reaction, we designed a RNA oligonucleotide (UUUAUU) and this RNA was cleavage activity at the U-A sequence.

Ammonium Chloride↗

PubMed1996

Mutations of the transforming growth factor-beta type II receptor gene are strongly related to sporadic proximal colon carcinomas with microsatellite instability.

BACKGROUND: Mutations of the transforming growth factor-beta type II receptor gene (TGF-beta RII) have been found in several replication error-positive sporadic colorectal carcinomas and hereditary nonpolyposis colorectal carcinoma cell lines. The aim of this study was to clarify the role of TGF-beta RII in sporadic colorectal carcinogenesis. METHODS: The authors screened for mutations at simple repeated sequences in the TGF-beta RII gene by polymerase chain reaction-single strand conformation polymorphism. They also examined genomic instability, using five microsatellite DNA markers in 69 sporadic colorectal carcinomas. When the carcinomas exhibited the TGF-beta RII mutations, the authors screened further for mutations in two DNA mismatch repair genes, hMSH2 and hMLH1. RESULTS: Seven of the 69 cancers (10%) showed one or two A deletions in TGF-beta RII and resultant frameshift mutations in nucleotide positions 709-718 containing a (A) 10 repeated sequence; but none of these appeared in the corresponding normal DNA, indicating a somatic mutation. All of the seven cancers were located in the proximal colon; there were none in the distal colon (P < 0.01). On the other hand, 22 of the 69 carcinomas (32%) showed the replication error-positive phenotype. The frequency of replication errors in proximal colon carcinomas was higher than that in distal colon carcinomas (P < 0.05). All 7 cancers with TGF-beta RII mutations showed replication errors. One of them revealed a nonsense mutation at codon 413, and 1 revealed a loss of heterozygosity in hMSH2. CONCLUSIONS: These data indicate that mutations of TGF-beta RII are strongly related to proximal colon carcinomas with microsatellite instability and that the mechanism of carcinogenesis in some proximal colon carcinomas is similar to that in hereditary nonpolyposis colorectal carcinoma.

Aged↗

PubMed1996

Comparisons on chemically-induced mutagenicity among four bacterial strains, Salmonella typhimurium TA102 and TA2638, and Escherichia coli WP2/pKM101 and WP2 uvrA/pKM101: collaborative study I.

A collaborative study of chemically-induced mutagenicity was performed using the four bacterial strains Salmonella typhimurium TA102 and TA2638 and Escherichia coli WP2/pKM101 and WP2 uvrA/pKM101 in order to compare the specific spectrum of response to chemicals among the four strains and to determine the usefulness (sensitivity) of each strain. Twenty laboratories participated in this study. As the first step, 29 compounds were tested for mutagenicity using the plate incorporation method with or without metabolic activation. The compounds consisted of 12 chemicals judged previously positive only in E. coli WP2 uvrA/pKM101, 15 of their derivatives, and the 2 well-known mutagens hydrazine and formaldehyde. The strains and the chemicals were sent from a central source to each laboratory. The tests were performed in two laboratories per chemical. Concerning the result with each strain, the number of chemicals which showed mutagenic activity were 10, 7, 9 and 17 in TA102, TA2638, WP2/pKM101 and WP2 uvrA/pKM101, respectively. Among these 29 compounds tested, no qualitative difference in the response to chemicals among the four strains was observed with 17 compounds, being 12 negative chemicals and 5 positive chemicals. The remaining 12 compounds showed varying results among the four strains. On the comparison of TA102 and WP2 uvrA/pKM101, the same qualitative response to chemicals was observed with 22 compounds. Thus, although compounds tested in this study were selected, partly based on a previously-judged positive response only in E. coli WP2 uvrA/pKM101, 76% of test chemicals showed the same sensitivity in TA102, 7 chemicals (24%) were only positive in the E. coli strains. Of these 7 chemicals, 5 were the acrylic acid ester derivatives and the chloroacetic acid ester derivatives possessing a common structure of a functional group esterized between acid and alcohol with two or more carbon radicals.

Escherichia coli↗

PubMed1996

Suppression of prostaglandin E receptor signaling by the variant form of EP1 subtype.

A cDNA clone of prostaglandin (PG) E receptor EP1 subtype (rEP1) was isolated from a rat uterus cDNA library. It encodes 405 amino acid residues with seven transmembrane-spanning domains and couples to Ca2+ mobilization. In addition, three cDNA clones encoding a variant form of rEP1 were isolated. The open reading frame can code a 366-amino acid protein carrying a specific change of 49 amino acids from the middle of transmembrane segment VI to COOH terminus; it possesses a transmembrane segment VII-like structure lacking an intracellular COOH-terminal tail. Southern blot analysis of rat genomic DNA and genomic polymerase chain reaction demonstrated that these cDNAs were derived from a single copy gene. Northern blot analysis and ribonuclease protection assay revealed that both rEP1 and rEP1-variant receptor mRNAs were highly expressed in the kidney. Immunoblot with an antibody directed toward the specific region of rEP1-variant receptor showed that rEP1-variant receptor protein was expressed in the membrane of the kidney and Chinese hamster ovary (CHO) cells transfected with rEP1-variant cDNA. Thus, the rEP1-variant receptor is translated from mRNA which is not spliced at nucleotide position 952 in the segment VI transmembrane region. rEP1-variant receptor retained the ligand binding activity with affinity and specificity similar to rEP1 receptor, but lost the coupling of signal transduction systems by itself. However, when rEP1-variant receptor was stably co-expressed with rEP1 receptor in CHO cells, the Ca2+ mobilization mediated by EP1 receptor was significantly suppressed. Furthermore, when rEP1-variant receptor was expressed in CHO cells, cAMP formation by activation of endogenous EP4 receptor was strongly blocked. These results suggest that the rEP1-variant receptor may affect the efficiency of signal coupling of PGE receptors and attenuate the action of PGE2 on tissues.

Amino Acid Sequence↗

PubMed1996

Changes in trough levels of whole blood cyclosporine and graft function of a kidney transplant recipient with onset of hypothyroidism after transplantation.

The immunosuppressive and toxic effects of cyclosporine (CsA) are affected by many factors. We present the first case of a kidney transplant patient who had an onset of hypothyroidism about two months after the transplantation. In this case, trough levels of whole blood CsA and total serum cholesterol levels increased at the same time. But the decrease in renal function was not as severe as expected from the very high trough levels of whole blood CsA. Elevation of the trough level of whole blood CsA may be due to a decrease in CsA clearance resulting from the decreased cytochrome P-450 activity in hypothyroidism. Furthermore, a decrease in thyroid hormone level and increase in plasma lipoprotein level might have affected the distribution of CsA, and this change might have influenced the toxic effect of CsA In conclusion, our case suggests that thyroid function and plasma lipoprotein level should be considered important factors that affect the pharmacokinetics and action of CsA.

Adult↗

PubMed1996

Probing substrate binding site of the Escherichia coli quinol oxidases using synthetic ubiquinol analogues.

Substrate binding sites of the Escherichia coli bo- and bd-type quinol oxidases were probed with systematically synthesized ubiquinol analogues. The apparent Km values of ubiquinol-2 derivatives to the bo-type enzyme were much lower than that of the corresponding 6-n-decyl derivatives. The isoprenoid structure is less hydrophobic than the saturated n-alkyl group with the same carbon number; therefore, the native isoprenoid side chain appears to play a specific role in quinol binding besides simply increasing hydrophobicity of the molecule. The Vmax values of 2-methoxy-3-ethoxy analogues were greater than that of 2-ethoxy-3-methoxy analogues irrespective of the side chain structure. This result indicates not only that a methoxy group in the 2-position is recognized more strictly than the 3-position by the binding site but also that the side chain structure does not affect binding of the quinol ring moiety. Systematic analysis of the electron-donating activities of the analogues with different substituents in the 5-position revealed that the 5-methyl group is important for the activity. In the parallel studies with the bd-type enzyme, we obtained similar observations except that almost all quinol analogues, but not ubiquinol-1, elicited a remarkable substrate inhibition at higher concentrations. These results indicate that the two structurally unrelated terminal oxidases share common structural properties for the quinol-oxidation site.

Electrons↗

PubMed1996

Dose-dependent induction of recessive mutations with N-ethyl-N-nitrosourea in primordial germ cells of male mice.

Using a specific locus test, we previously found that N-ethyl-N-nitrosourea (ENU) induces recessive mutations at a relatively high rate in male mouse primordial germ cells (PGC) at 8.5, 10.5 and 13.5 days of development (G8.5, G10.5 and G13.5). A large difference was observed on the induced mutation rate between 30 and 50 mg/kg ENU in 10.5-day PGC. We therefore carried out specific locus tests to ascertain whether ENU induces recessive mutations in a dose-dependent manner in G8.5 and G10.5 PGC. We also gave multiple doses of 25 mg/kg ENU using an 18-h interval, the approximate doubling time of PGC at these developmental stages, to test for an additive effect on the induced mutations rate. A dose-dependent induction of recessive mutations by ENU was observed in both G8.5 and G10.5 PGC, and multiple dosing of 25 mg/kg ENU showed an additive effect. Comparing these results to data on spermatogonial stem cells, we conclude the capacity to repair ENU-induced premutagenic damages is less effective in male mouse PGC at these developmental stages than in spermatogonial stem cells.

Animals↗

PubMed1996

An antibiotic-binding motif of an RNA fragment derived from the A-site-related region of Escherichia coli 16S rRNA.

A small RNA derived from the decoding region of Escherichia coli 16S rRNA can bind to antibiotics of aminoglycosides (neomycin and paromomycin) that act on the small ribosomal subunit [Purohit,P. and Stern,S. (1994) Nature, 370, 659-662]. In the present study, the P-site subdomain was removed from this decoding region RNA to construct a 27mer RNA (designated as ASR-27), which includes the A-site-related region (positions 1402-1412 and 1488-1497) of 16S rRNA. Footprint experiments with dimethyl sulfate as a chemical probe indicated that the ASR-27 RNA can interact with the neomycin family in the same manner as the decoding region RNA. A mutagenesis analysis of the ASR-27 RNA revealed that paromomycin binding of ASR-27 involves the C1407.G1494 and C1409-G1491 base pairs, and the internal loop comprising A1408 and the nucleotides in positions 1492-1493, located between the two C.G base pairs. In addition, a G or U in position 1495, and base pairing between positions 1405 and 1496 are also involved. These structural features were found in a viral RNA element, the Rev-binding site of human immunodeficiency virus type-1, which may explain why neomycin can bind to this viral RNA.

Aminoglycosides↗

PubMed1996

NMR studies of the effects of the 5'-phosphate group on conformational properties of 5-methylaminomethyluridine found in the first position of the anticodon of Escherichia coli tRNA(Arg)4.

5-Methylaminomethyluridine (mnm5U) exists in the first position of the anticodon (position 34) of Escherichia coli tRNA4Arg for codons AGA/AGG. In the present study, the temperature dependence of the ribose-puckering equilibrium of pmnm5U was analyzed by proton NMR spectroscopy. Thus, the enthalpy difference (delta H) between the C2'-endo and C3'-endo forms was obtained at 0.65 kcal.mol-1. By comparison of the delta H values of pU and pmnm5U, the 5-substitution was found to increase the relative stability of the C3'-endo form over the C2'-endo form significantly (by 0.56 kcal.mol-1). Furthermore, this conformational "rigidity" was concluded to depend on the 5'-phosphate group, because nucleoside U exhibits only a negligible change in the ribose-puckering equilibrium upon the 5-methylaminomethyl substitution. Further NMR analyses and molecular dynamics calculations revealed that interactions between the 5-methylaminomethyl and 5'-phosphate groups of pmnm5U restrict the conformation about the glycosidic bond to a low anti form, enhancing steric repulsion between the 2-carbonyl and 2'-hydroxyl groups in the C2'-endo form. This intrinsic conformational rigidity of the mnm5U residue in position 34 may contribute to the correct codon recognition.

Anticodon↗

PubMed1996

Comparison of the structural features of ubiquinone reduction sites between glucose dehydrogenase in Escherichia coli and bovine heart mitochondrial complex I.

To characterize the structural features of the ubiquinone reduction site of glucose dehydrogenase (GlcDH) in Escherichia coli, we performed structure/activity studies of a systematic set of synthetic ubiquinone analogues and specific inhibitors (synthetic capsaicins) of this site. Considering the proposed similarity of the quinone binding domain motif between GlcDH and one subunit of mitochondrial complex I [Friedrich, T., Strohdeicher, M., Hofhaus, G., Preis, D., Sahm, H. & Weiss, H. (1990) FEBS Lett. 265, 37-40], we compared the structure/activity profiles of the substrates and inhibitors for GlcDH with those for bovine heart mitochondrial complex i. With respect to GlcDH, replacement of one or both methoxy groups in the 2 and 3 positions of benzoquinone ring by ethoxy group(s) resulted in a drastic decrease in the electron accepting activity. The presence of a 5-methyl group and the conformational property of the 6-alkyl side chain did not significantly contribute to the activity. These results suggested that only half of the benzoquinone ring (the moiety corresponding to the 2 and 3 positions) is recognized by the quinone reduction site in a strict sense. In contrast, quinone analogues with structural modifications at all positions in the benzoquinone ring retained the activity with mitochondrial complex I. This finding indicated that the catalytic site of complex I is spacious enough to accommodate a variety of structurally different quinone derivatives. The correlation of the inhibitory potencies of a series of synthetic capsaicins between the two enzymes was very poor. These findings indicated that the binding environment of ubiquinone in GlcDH is very specific and differs from that in mitochondrial complex I.

Animals↗

PubMed1996

Major identity determinants in the "augmented D helix" of tRNA(Glu) from Escherichia coli.

By a kinetic analysis of 59 variant transcripts of Escherichia coli tRNA(Glu) with glutamyl-tRNA synthetase (GluRS), the U11.A24 base-pair, the U13.G22..A46 base-triple, and the lack of residue 47 (delta47) were found to serve as major determinants for tRNA(Glu) identity. This is the first system for which major identity determinants are reported to be clustered in the "augmented D helix", consisting of the D stem with some neighboring residues and the variable loop. Other identity determinants are U34, U35, C36 and A37 in the anticodon loop, and G1.C72 and U2.A71 in the acceptor stem. Phosphate-group protection by GluRS from ethylnitrosourea was observed most strongly for the minor groove side of D-stem helix, indicating that GluRs tightly binds to the D stem for recognition, on the minor groove side, of the potent identity-determinant groups of the U11.A24 and U13.G22 base-pairs. A46 is not involved in direct recognition by GluRS; the U13.G22..A46 base-triple is required probably for formation of the structural features that are recognized by GluRS. In this context, the essential role of characteristic delta47 in tRNA(Glu) identity may be to maintain the U13.G22..A46 base-triple.

Anticodon↗

PubMed1996

An allel-specific abnormal transcript of the heat shock protein 70 gene in patients with major depression.

Stress-inducible 72-kDa heat shock proteins (HSP70) were encoded on genes in multiple chromosomes. The expression of mRNA transcribed from the gene (HSP70-1) on chromosome 6 was studied using reverse transcript polymerase chain reaction in peripheral blood mononuclear cells of patients with different diseases. The deletion of 29 bp occurred in 5' noncoding and subsequent 133 bp in coding sequences of HSP70 mRNA in patients with major depression (n = 18), while normal subjects (n = 10) and patients with schizophrenia (n = 5), essential hypertension (n = 3), rheumatoid arthritis (n = 7), and Graves' disease (n = 3) had normal mRNA. No such deletion occurred in genomic DNA and no protein was translated from deleted mRNA. The allel-specific abnormal transcript of the HSP70 gene on chromosome 6 thus may underlie the altered stress and/or immune response in major depression.

Alleles↗