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Biomedical subjects

Y Sekine

Publications and source records attributed to Y Sekine.

At least 73 records · Page 4Linked to original sources

Magnitude of the regression to the mean within one-year intra-individual changes in serum lipid levels among Japanese male workers.

To investigate the magnitude of the 'regression to the mean' effect for the changes in serum total cholesterol (TC), triglycerides (TG), and high density lipoprotein cholesterol (HDLC) levels during one-year interval between annual health check-ups in occupational settings, the relationships between the baseline level and subsequent one-year change in TC, TG or HDLC were analyzed using paired health check-up data in 1998 and 1999 of 547 Japanese male clerical workers. After adjustment for age, body mass index (BMI), yearly change in BMI, drinking score and smoking score by the multivariate analyses, the yearly changes in each serum lipid (deltaTC, deltaLn(TG) or deltaHDLC) were clearly inversely associated with the lipid levels in 1998. For example, in the multiple linear regression analyses setting delta value in each serum lipid as a dependent variable, the partial regression coefficients for the baseline lipid levels (beta1) were - 0.21 (p<0.001) for the TC, -0.39 (p<0.001) for the Ln(TG) and -0.15 (p<0.001) for the HDLC, respectively. These results suggest that the observed yearly change in each serum lipid level may largely reflect the 'regression to the mean' effect in addition to the real yearly biological change.

Adult↗

Role of ribosome recycling factor (RRF) in translational coupling.

RNA phage GA coat and lysis protein expression are translationally coupled through an overlapping termination and initiation codon UAAUG. Essential for this coupling are the proximity of the termination codon of the upstream coat gene to the initiation codon of the lysis gene (either a <3 nucleotide separation or physical closeness through a possible hairpin structure) but not the Shine-Dalgarno sequence. This suggests that the ribosomes completing the coat gene translation are exclusively responsible for translation of the lysis gene. Inactivation of ribosome recycling factor (RRF), which normally releases ribosomes at the termination codon, did not influence the expression of the reporter gene fused to the lysis gene. This suggests the possibility that RRF may not release ribosomes from the junction UAAUG. However, RRF is essential for correct ribosomal recognition of the AUG codon as the initiation site for the lysis gene.

Amino Acid Sequence↗

Mutations influencing the frr gene coding for ribosome recycling factor (RRF).

A total of 52 null, six reversion, and five silent mutations of frr (the gene encoding for ribosome recycling factor (RRF)) of Escherichia coli are discussed along with 12 temperature-sensitive (ts) mutations and 14 intergenic suppressor strains of ts RRF. The null mutations were classified into six different categories. A computer-based secondary structure analysis showed three domains; domain A which has the N-terminal helix, domain B which contains coil, alpha-helix and beta-strand structure, and domain C which is a C-terminal helix. The ts mutations fell into domains A and C but not in domain B. More than a half of the null mutations fell into domain B while the silent mutations fell outside domain B. Substitution of Arg132 in domain C by other amino acids was observed among five independently isolated null mutants. It is suggested that domain B is important for maintaining the RRF structure, while the region including Arg132 is one of the active sites. A total of 14 intergenic suppressor strains of ts RRF were grouped into four categories, depending on which temperature-sensitive alleles were suppressed.

Amino Acid Sequence↗

Evaluation of pulmonary gas exchange after lobectomy and simple thoracotomy.

Postoperative influence of simple thoracotomy and lobectomy on pulmonary gas exchange was investigated in 10 patients undergoing thoracotomy and lobectomy (L group) and 10 patients with simple thoracotomy (ST group). Gas exchange was assessed with hot-wire mass spectrometry and blood gas analyses preoperatively and postoperatively at 1, 3, 6, 12, 24 and 48 h and on days 4, 6 and 13. The preoperative values of alveolar-arterial oxygen tension gradient (AaDO2), ventilation-perfusion mismatch (V(A)/Q) and circulatory shunt (Qs/Qt) were maintained in the ST group. In the L group, however, AaDO2 and Qs/Qt showed good maintenance of gas exchange for only 6-12h after lobectomy and then deteriorated because of peripheral atelectasis, resulting in poorer values than those in the ST group on days 4 and 13. Careful postoperative management, including pulmonary toilet, is essential for maintenance of gas exchange and prevention of pulmonary complications.

Adult↗

Postprandial hyperlipidemia in streptozotocin-induced diabetic rats is due to abnormal increase in intestinal acyl coenzyme A:cholesterol acyltransferase activity.

Postprandial hyperlipidemia (PH) is recognized as a significant risk factor for cardiovascular disease. The present study, involving rats with streptozotocin (STZ)-induced diabetes, was performed to establish a PH model and to examine the relation between small intestinal acyl-coenzyme A:cholesterol acyltransferase (ACAT) activity and serum lipid levels in the postprandial state. The small intestinal ACAT activities in normal rats during the experimental period were 4 to 5 pmol/mg protein per minute. In contrast, in the diabetic rats, the ACAT activities were 2 to 3 times higher than activities seen in normal rats from 7 to 21 days after the STZ injection in the absence of a high fat diet and hyperplasia in the gut. In an oral fat-loading test that used diabetic rats that had been injected with STZ (60 mg/kg) intravenously 14 days previously, the postloading changes in the serum concentrations of total cholesterol (TC) and triglyceride (TG) were significantly greater in the diabetic rats than in normal rats. Single oral administration of (1s,2s)-2-[3-(2,2-dimethylpropyl)-3-nonylureido]cyclohexane- 1-yl 3-[(4R)-N-(2,2,5,5-tetramethyl-1, 3-dioxane-4-carbonyl)amino]propionate (F-1394, 3 to 30 mg/kg), a potent ACAT inhibitor, suppressed the post-fat-loading elevation of serum TC levels in the diabetic rats in a dose-dependent manner without affecting serum glucose levels. Furthermore, the small intestinal ACAT activity, serum TG levels, and lymphatic absorption of TC and TG in the rats that were administered F-1394 (30 mg/kg) were reduced by approximately 90%, 70%, 30%, and 15%, respectively. This is the first evidence that elevated ACAT activity in the gut, unlike hyperplasia and hyperphagia, induces PH in rats. Our results strongly suggest that F-1394 may be a potential treatment for PH in humans.

Animals↗

Monocyte chemoattractant protein-1 and RANTES are chemotactic for graft infiltrating lymphocytes during acute lung allograft rejection.

Graft infiltrating lymphocytes (GILs) are crucial to rejection of lung allografts. However, chemotactic activities, chemokines responsible for GIL recruitment, and cells involved in chemokine production during lung allograft rejection have not been evaluated. This study determined whether chemotactic activity for GILs is upregulated, and whether the chemokines monocyte chemoattractant protein (MCP)-1 and regulated on activation, normal T cells expressed and secreted (RANTES) have roles in GIL chemotaxis during lung allograft rejection. F344 (RT1(lv1)) rat lung allografts were transplanted into WKY (RT1(l)) recipients. Chemotactic activity for GILs and quantities of MCP-1 and RANTES were determined in allograft bronchoalveolar lavage fluid 1 wk after transplantation. Data showed that during rejection, chemotactic activity for GILs is upregulated, MCP-1 and RANTES are produced locally, and both MCP-1 and RANTES are operative in GIL recruitment. Immunohistochemistry showed that alveolar macrophages (AMs) were the major source of MCP-1 and that other lung cells, including AMs, were the source of RANTES. Further, depletion of AMs in the donor lung before transplantation downregulated chemotaxis for GILs and production of MCP-1 during rejection episodes. These data show that chemotaxis for GILs is upregulated locally during lung allograft rejection, and that MCP-1 and RANTES contribute to GIL recruitment during the rejection response.

Animals↗

Linearization and transposition of circular molecules of insertion sequence IS3.

IS3 transposase has been shown to promote production of characteristic circular and linear IS3 molecules from the IS3-carrying plasmid; IS3 circles have the entire IS3 sequence with terminal inverted repeats, IRL and IRR, which are separated by a three base-pair sequence originally flanking either end in the parental plasmid, whereas linear IS3 molecules have three nucleotide overhangs at their 5' ends. Here, we showed that a plasmid carrying an IS3 derivative, which is flanked by different sequences at both ends, generated IS3 circles and linear IS3 molecules owing to the action of transposase. Cloning and sequencing analyses of the linear molecules showed that each had the same 5'-protruding three nucleotide overhanging sequences at both ends, suggesting that the linear molecules were not generated from the parental plasmid by the two double-strand breaks at both end regions of IS3. The plasmid carrying IS3 with a two base-pair mutation in the terminal dinucleotide, which would be required for transposase to cleave the 3' end of IS3, could still generate linear molecules as well as circles. Plasmids bearing an IS3 circle were cleaved by transposase and gave linear molecules with the same 5'-protruding three nucleotide overhanging sequences. These show that the linear molecules are generated from IS3 circles via a double-strand break at the three base-pair intervening sequence. Plasmids carrying an IS3 circle with the two base-pair end mutation still were cleaved by transposase, though with reduced efficiencies, suggesting that IS3 transposase has the ability to cleave not only the 3' end of IS3, but a site three nucleotides from the 5' end of IS3. IS3 circles also were shown to transpose to the target plasmids. The end mutation almost completely inhibited this transposition, showing that the terminal dinucleotides are important for the transfer of the 3' end of IS3 to the target as well as for the end cleavage.

Base Pairing↗

Sigmoid colon cancer presenting as complete rectal prolapse: report of a case.

We describe herein the unusual case of a 76-year-old woman who was diagnosed as having sigmoid colon cancer after presenting with complete rectal prolapse. The rectal prolapse was considered to have been caused by constipation accelerated by the colon cancer. The relationship between colorectal cancer and rectal prolapse has not yet been clarified; however, this case report suggests that rectal prolapse can present as a symptom of colorectal cancer. Thus, patients with a sudden onset of rectal prolapse should be screened for colorectal cancer.

Aged↗

Correlations between in vitro affinity of antipsychotics to various central neurotransmitter receptors and clinical incidence of their adverse drug reactions.

OBJECTIVE: This study was performed to determine whether in vitro affinities of currently available antipsychotics toward dopamine or other neuronal receptor systems are associated with their in vivo incidence of central and peripheral adverse drug reactions (ADRs). METHODS: For 17 antipsychotic drugs available in Japan, the clinical incidences of 7 different types of drug-induced ADRs (i.e., akathisia, dyskinesia, tremor, rigidity, drowsiness, hypotension and dry mouth) were obtained from both post-marketing ADR databases and the investigational clinical trials of eight pharmaceutical companies. Affinity constants (K(i)) of the respective drugs toward dopamine D(1) and D(2) receptors, alpha(1)-adrenoceptors, histamine H(1) receptors, serotonin 5-HT(2) receptors and muscarinic cholinoceptors, determined using rat brain synaptosomes, were obtained from the literature. Relationships between in vitro receptor-binding properties and in vivo incidences of the respective types of antipsychotic-related ADRs were analyzed using Spearman's rank correlation. RESULTS: Significant (P < 0.05) correlations were observed between the K(i) values for dopamine D(2) receptor and the clinical incidences of akathisia and dyskinesia (r(s) = -0.68 and -0. 66, respectively). Significant (P < 0.05) correlations were also observed between the K(i) values for alpha(1)-adrenoceptor and histamine H(1) receptor and the incidence of drowsiness (r(s)=-0.65 and -0.55, respectively), and between the K(i) values for three receptor systems (i.e., dopamine D(1) receptor, alpha(1)-adrenoceptor and histamine H(1) receptor) and the incidence of dry mouth (r(s) = -0.50, -0.81 and -0.62, respectively). CONCLUSION: Preclinical receptor-binding data of antipsychotic drugs toward central dopamine and other ancillary neurotransmitter systems may be useful for predicting not only in vivo antipsychotic potency but also clinical incidence of akathisia and dyskinesia for this class of agents. Newly developed antipsychotic drugs with more potent and selective antagonistic activity against the dopamine D(2) receptor may not necessarily be associated with a lower incidence of extrapyramidal ADRs.

Adverse Drug Reaction Reporting Systems↗

A novel method of endoscopic mucosal resection using sodium hyaluronate.

BACKGROUND: Saline-assisted endoscopic mucosal resection is an established therapeutic method. However, it is sometimes difficult to maintain a desired level of tissue elevation after injection of saline. Therefore we decided to use a mucinous substance such as sodium hyaluronate instead of saline. METHODS: Two resected porcine stomachs and five dogs were used for the study. The elevations, made by submucosal injections of sodium hyaluronate, were compared with those produced with normal saline. Sodium hyaluronate-assisted mucosal resections were compared with the saline-assisted resections. RESULTS: Mucosal elevations created by submucosal injections of sodium hyaluronate remained for a longer time with a clearer margin compared to those made by saline injection. Endoscopic mucosal resections were performed safely with the assistance of sodium hyaluronate. CONCLUSIONS: Use of sodium hyaluronate instead of saline for endoscopic mucosal resection could make the procedure easier and more reliable.

Animals↗

Effects of intraocular or systemic administration of neutralizing antibody against vascular endothelial growth factor on the murine experimental model of retinopathy.

Vascular endothelial growth factor (VEGF), the strongest known angiogenic cytokine and also a potent enhancer of vascular permeability, is closely associated with diabetic ocular complications and other intraocular neovascular diseases. The therapeutic effect of VEGF-neutralizing antibody on oxygen-induced retinopathy in an experimental murine model of proliferative retinopathy was investigated. Intraocular and systemic injection of the antibody resulted in 46% and 18% reductions in the number of nuclei of newly formed vessels of this model, respectively. The results demonstrated that a neutralizing antibody against VEGF was highly effective in the treatment of intraocular neovascularization and suggested possible modes of therapy in human intraocular neovascular diseases, including diabetic proliferative retinopathy.

Animals↗

Prognostic factors in surgical treatment of solitary brain metastasis after resection of non-small-cell lung cancer.

Patients with brain metastasis after resection of non-small-cell lung cancer usually have poor prognosis. A few such patients, however, survive for long periods after surgical resection of brain metastases. To evaluate the prognostic factors in resection of solitary brain metastasis from non-small-cell lung cancer, we reviewed 24 cases undergoing resection of solitary brain metastasis after resection of the primary site from 1977 to 1993. The patient population consisted of 20 men and four women ranging in age from 40 to 75 years old (average, 57.8 years old). None of the patients had systemic metastasis except in the brain at the time of brain surgery. The overall survival rates were 12.5% at 3 years and 8.3% at 5 years after brain surgery. The longest survival periods were 11.5 years after brain surgery and 15.4 years after lung surgery. The interval between lung and brain surgery (< or =360 days vs. >360 days), differentiation of primary cancer (poor vs. moderate), size of primary site (< or =5.0 cm vs. >5.0 cm), and operation of primary site (lobectomy vs. pneumonectomy) significantly affected survival as shown by univariate analysis (P<0.05). Other clinical factors (age, gender, histology, T- and N-status, 'resectability with curative intent' of the primary site, location of the brain metastasis and postoperative radiation therapy) did not affect survival. Multivariate analysis using Cox's proportional hazards model indicated that an interval of more than 360 days between the two surgical procedures (hazard ratio = 0.2351, P = 0.0136) and lobectomy (hazard ratio = 0.5274, P = 0.0416) were independent prognostic factors. In conclusion, patients with solitary brain metastasis from non-small-cell lung cancer without other organ metastasis, in whom relapse in the brain occurred more than 1 year after resection of the primary site and in whom lobectomy was performed, should be treated surgically to maximize the chance of prolonged survival.

Adenocarcinoma↗

Video-assisted thoracoscopic surgery does not deteriorate postoperative pulmonary gas exchange in spontaneous pneumothorax patients.

OBJECTIVES: Video-assisted thoracoscopic surgery (VATS) is generally recognized as a less invasive method than thoracotomy. However, the influence of VATS on postoperative pulmonary gas exchange has yet to be evaluated. METHODS: Thirty eight patients with spontaneous pneumothorax were randomized into bullectomy by VATS (n = 20) or axillary thoracotomy (n = 18). Gas exchange was assessed by using hot wire mass spectrometer, and blood gas analysis preoperatively and postoperatively at 1, 3, 6, 12, 24, and 48 h and on days 4 and 6. Post operative pain control was managed by continuous epidural morphine injection and administration of diclofenac sodium orally or suppository. Postoperative atelectasis was assessed by daily chest roentgenograms. RESULTS: VATS patients had continuously higher PaO2 than axillary thoracotomy at 12, 48 h and day 4 postoperatively (P < 0.05). Alveolar-arterial oxygen tension gradient in VATS patients was significantly less than that in patients with axillary thoracotomy from the 6th h throughout to the 4th day postoperatively (P < 0.01). Use of postoperative analgesics and the incidence of peripheral atelectasis were more frequent in patients with axillary thoracotomy. CONCLUSIONS: Bullectomy via VATS was less deleterious to pulmonary gas exchange. Axillary thoracotomy caused worsening of gas exchange postoperatively due to incisional pain, chest wall deformity, and peripheral atelectasis.

Adult↗

Transposition of IS1 circles.

BACKGROUND: IS1, the smallest active transposable element in bacteria, encodes transposase. IS1 transposase promotes transposition as well as production of miniplasmids from a plasmid carrying IS1 by deletion of the region adjacent to IS1. The IS1 transposase also promotes production of IS1 circles consisting of the entire IS1 sequence and a sequence, 6-9 bp in length, as a spacer between terminal inverted repeats of IS1. The biological significance of the generation of IS1 circles is not known. RESULTS: Plasmids carrying an IS1 circle with a spacer sequence 6-9 bp long transposed to target plasmids at a very high frequency when transposase was produced from a co-resident plasmid. The products were target plasmids with the donor plasmid inserted at the ends of IS1 in the IS1 circle. This insertion accompanied the removal of the spacer sequence and duplication of the sequence at the target site. IS1 circles with a much longer spacer sequence transposed less frequently. The SOS response was induced in cells harbouring a plasmid with an IS1 circle owing to transposase. IS1 circles could transpose in the strain deficient in H-NS, a nucleoid-associated DNA-binding protein known to be required for the transposition of IS1. CONCLUSIONS: IS1 circles appear to act as intermediates for simple insertion into the target DNA via cleavage of the circles which induces the SOS response. H-NS may function in promoting the assembly of an active IS1 DNA-transposase complex at the terminal inverted repeats.

Bacterial Proteins↗