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Biomedical subjects

S Hara

Publications and source records attributed to S Hara.

At least 55 records · Page 3Linked to original sources

Plasma growth hormone (GH) responses after administration of the peptidergic GH secretagogue KP102 into the oral cavity, rumen, abomasum and duodenum in adult goats.

The study was performed to determine whether orally administered KP102 (also known as GHRP-2) stimulates GH release in adult goats, and how the orally administered KP102 passes through the digestive tract and stimulates GH release in ruminant animals. Five mg/kg body weight (BW) of KP102 dissolved in 9 ml of saline were administered into the oral cavity, rumen, omasum and duodenum of adult goats, and GH release after administration of KP102 was examined. The GH levels were significantly elevated at 20 min after administration of KP102 into the oral cavity, and plasma concentrations of GH remained significantly elevated until 60 min (P < 0.05). The GH levels after administration of KP102 into the abomasum were variable. However, the GH level tended to increase within 30 min after administration, and were significantly higher than those of controls after 120 to 150 min (P < 0.05). The GH levels after administration of KP102 into the duodenum were significantly elevated at 40 min after administration, and plasma concentrations of GH remained significantly elevated until 140 min (P < 0.05). The administration of KP102 into the rumen failed to stimulate GH release. The GH response curves (AUC) produced after administration of KP102 into the abomasum or duodenum were 2.2-fold greater than those for after administration into the oral cavity (P < 0.05). The oral administration of 5 mg/kg BW of KP102 in the powder state, not dissolved in 9 ml of saline, failed to stimulate GH release. These results suggested that orally administered KP102 dissolved in saline transiently stimulates GH release in adult goats, and this phenomenon might be due to small amounts of the peptides entering directly into the abomasum with liquid bypassing the rumen.

Abomasum↗

Perineural injection to nerve root and radicular blood flow: a clinical study during spinal surgery.

BACKGROUND AND OBJECTIVE: To investigate the effects of the perineural injection of lidocaine or corticosteroids on radicular blood flow during spinal surgery. METHODS: After lumbar discectomy, a probe for laser Doppler flowmetry was placed directly on the 4th or 5th lumbar nerve root. Thirty patients undergoing lumbar discectomy were randomly assigned to one of three groups. Each group received one of three protocols for a perineural injection to the nerve root: 1.0 mL 0.9% saline in group A, 1.0 mL 1% lidocaine in group B or 1.0 mL dexamethasone (4 mg) in group C. Measurements included radicular blood flow, mean arterial pressure, haemoglobin concentration, percutaneous oxygen saturation and end-tidal carbon dioxide tension. Radicular blood flow was measured by laser Doppler flowmetry before the injection and 15 min after these injections. The three groups were similar with respect to mean arterial pressure, haemoglobin concentration, percutaneous oxygen saturation and end-tidal carbon dioxide tension. RESULTS: Radicular blood flow did not change after the injection in any of the groups. CONCLUSIONS: The results suggest that the perineural injection of 1% lidocaine or dexamethasone does not affect radicular blood flow during lumbar discectomy.

Adrenal Cortex Hormones↗

Presence of natural killer-cell clones with variable proliferative capacity in chronic active Epstein-Barr virus infection.

Chronic active Epstein-Barr virus infection (CAEBV) is a syndrome that takes diverse clinical courses and is often associated with lymphoproliferative disorders of T/natural killer (NK)-cell lineage. We describe a patient with CAEBV associated with persistent pharyngeal ulcer, and with subsequent nasal T/NK-cell lymphoma in her neck lymph nodes and nasopharynx. Immunophenotyping of lymphoid cells showed that the lineage of Epstein-Barr virus (EBV)-positive cells in the patient was of NK-cell origin. By means of high-dose recombinant interleukin-2, we established an EBV-positive cell line of NK-cell lineage from her peripheral blood. Southern blot analysis for the number of terminal repeat sequences of EBV detected three NK-cell clones in the patient's lymph node. One of these clones was identical to the established cell line but was not observed in the pharyngeal ulcer, while the other two clones were present in the pharyngeal ulcer. These results suggest that the patient had expansion of the three NK-cell clones, one of which had proliferative capacity in vitro and was involved in the formation of the lymphoma. Moreover, the results suggest that the proliferative capacity of EBV-positive cells can be variable even in a single patient, and this variability may explain the clinical diversity in CAEBV.

Adult↗

Value of prostate specific antigen alpha1-antichymotrypsin complex for the detection of prostate cancer in patients with a PSA level of 4.1-10.0 ng/mL: comparison with PSA-related parameters.

BACKGROUND: The aim of the present study was to evaluate the usefulness of prostate specific antigen alpha1-antichymotrypsin complex (PSA-ACT) in the differential diagnosis of prostate cancer in patients with a PSA level of 4.1-10.0 ng/mL compared to several PSA- and PSA-ACT-related parameters. METHODS: Serum samples were obtained from 103 patients with no evidence of malignancy on biopsy and 29 with histologically confirmed prostate cancer. All patients had pretreatment serum PSA levels between 4.0 and 10.0 ng/mL. The different forms of serum PSA, including total PSA (tPSA), free PSA (fPSA) and PSA-ACT were measured using immunofluorometric techniques with different monoclonal antibodies against PSA and ACT. Furthermore, tPSA and PSA-ACT densities of the whole prostate (PSAD and ACTD, respectively) and the f-to-tPSA and the f-to-PSA-ACT ratios (F/T ratio and F/ACT ratio, respectively) were calculated. RESULTS: The differences between patients with prostate cancer and benign prostatic disease were significant with respect to all six parameters examined in this study. Analysis of receiver operating characteristics revealed that the areas under the curve for PSA-ACT, ACTD and the F/ACT ratio were larger than those for tPSA, PSAD and the F/T ratio, respectively. However, there were no significant differences in discrimination between benign and malignant diseases among these six parameters. CONCLUSIONS: In patients who have an intermediate serum PSA level, PSA-ACT and its associated parameters may not be significantly superior in the differential diagnosis between prostate cancer and benign prostatic diseases compared to tPSA and its traditional relatives.

Aged↗

Value of the serum prostate-specific antigen-alpha 1-antichymotrypsin complex and its density as a predictor for the extent of prostate cancer.

OBJECTIVE: To determine whether serum levels of the prostate-specific antigen-alpha1-antichymotrypsin complex (PSA-ACT) and its density (ACTD) in patients scheduled to undergo radical prostatectomy for clinically localized prostate cancer can predict organ-confined vs extraprostatic disease. PATIENTS AND METHODS: Serum samples were obtained from 62 patients with clinically localized prostate cancer before they underwent radical prostatectomy. PSA and PSA-ACT were measured using immunofluorometric techniques with different monoclonal antibodies against PSA and ACT, respectively. Furthermore, the PSA and PSA-ACT densities of the whole prostate (PSAD and ACTD, respectively) were calculated. The relationships of serum PSA, PSA-ACT, PSAD, ACTD and the pathological stage of the prostatectomy specimens were analysed. RESULTS: The disease was organ-confined or extraprostatic in 30 and 32 men, respectively. In men with organ-confined cancer, the mean PSA and PSA-ACT levels were significantly lower than in those with extraprostatic disease. Furthermore, there were significantly higher mean PSAD and ACTD levels in men with extraprostatic than with organ-confined disease. There were also significant differences in PSA, PSA-ACT, PSAD and ACTD levels at each pathological stage, whereas there was no significant association between these variables and the Gleason score. Receiver-operating characteristic curve analysis for detecting organ-confined disease showed that PSA-ACT and ACTD had a larger area under the curve than PSA and PSAD, respectively, but these differences were not significant. Furthermore, PSA-ACT and ACTD provided significantly better sensitivity for detecting organ-confined disease than PSA and PSAD, respectively. CONCLUSIONS: Measuring PSA-ACT and ACTD may improve the preoperative evaluation of patients scheduled to undergo radical prostatectomy, because these factors better differentiate extraprostatic from organ-confined disease than PSA and PSAD.

Aged↗

Alternans of ventricular gradient during percutaneous transluminal coronary angioplasty.

We evaluated the influence of local myocardial ischemia induced by acute coronary occlusion during percutaneous transluminal coronary angioplasty (PTCA) on the ventricular gradients (VG) and investigated whether 2:1 alternans of VG occurs. Twenty-seven patients with angina pectoris, who had one-vessel coronary artery stenosis, were studied. The VG of each consecutive heartbeat before, during, and after PTCA over a 22-second interval was calculated using a microcomputer. The standard deviation and coefficient of variation of magnitude were used as indices of VG variability. Frequency-domain analysis of time series consisting of beat-to-beat VG magnitude for a 22-second interval was also performed by the maximum entropy method. The standard deviation and coefficient of variation of VG magnitude during PTCA were significantly greater than those before and after PTCA (P <.01, P <.01, respectively), and the indices before PTCA were also significantly greater than those after PTCA (P <.05). The maximum power spectrum peaks around 0.5 cycles/beat during PTCA were significantly greater than those after PTCA (P <.01); this suggests that the enhancement of VG alternans is reflected by 2:1 alternans of the action potential in the acute local ischemic myocardium during PTCA.

Adult↗

Usefulness of Ureteropyeloscopy for diagnosis of upper urinary tract tumors.

BACKGROUND: Upper urinary tract tumors have historically been diagnosed using urinary cytology examination and radiography. As the technique and instrumentation of ureteroscopic inspection and biopsy have advanced, ureteroscopic examination has become more routine. We studied the applicability and safety of using ureteropyeloscopy to diagnose upper urinary tract tumors. PATIENTS AND METHODS: Between January 1994 and October 1999, 50 patients at Kobe University Hospital underwent ureteropyeloscopy for suspected upper urinary tract tumors. RESULTS: The sensitivity values of radiography, urinary cytology, and ureteroscopy were 96%, 60%, and 92%, respectively. The specificity values of the three procedures examination were 12%, 84%, and 88%, respectively. No major complications or dissemination of malignant cells were evident. CONCLUSION: Ureteroscopic examination is a safe, sensitive, and specific means of detecting upper urinary tract tumors.

Adult↗

Acquisition of resistance to Fas-mediated apoptosis by overexpression of clusterin in human renal-cell carcinoma cells.

Recent studies have shown the antiapoptotic activity of clusterin against a wide variety of stimuli; however, the functional role of clusterin in Fas-mediated apoptosis has not been well characterized. We transfected the clusterin cDNA into human renal-cell carcinoma (RCC) ACHN cells that scarcely express clusterin protein in order to examine whether overexpression of clusterin inhibits the Fas-mediated signal pathway for apoptotic cell death. No significant difference was observed in the in vitro cell growth rates between the clusterin-transfected cell line (ACHN/CL) and the vector-only-transfected control cell line (ACHN/C), whereas the colony-forming efficiency in soft agar of ACHN/CL was significantly higher than that of ACHAN/C. The anti-Fas monoclonal antibody CH11 induced apoptosis in ACHAN/C cells in a dose-dependent manner; however, the growth-inhibitory effect of CH11 on ACHN/CL cells was markedly suppressed, with corresponding increases in p53 expression and decrease in the fraction of cells in the sub-G(1) phase of the cell cycle. Furthermore, the cytotoxic effect of CH11 on ACHN/CL cells was augmented by treatment with interferon-gamma, but a corresponding effect on ACHN/C cells was not observed. These findings suggest that overexpression of clusterin may contribute to a phenotype resistant to Fas-mediated apoptosis, and that if interferon-gamma treatment is added according to the clusterin expression level, Fas-mediated therapy could be a novel approach to RCC.

Adult↗

Prognostic variables in patients who have undergone radical cystectomy for transitional cell carcinoma of the bladder.

OBJECTIVE: To evaluate whether several clinicopathological factors could be used as prognostic predictors in patients who have undergone radical cystectomy for transitional cell carcinoma (TCC) of the bladder. METHODS: Between January 1985 and June 2000, 154 patients underwent radical cystectomy and pelvic lymphadenectomy for TCC of the bladder at a single institution. Their clinicopathological findings were analyzed based on the criteria of the Japanese Urological Association. RESULTS: Histopathological examination revealed that the tumor grade was 1 or 2 in 22 patients and 3 in 132 patients; the pathological stage was pT1 or less in 30 patients, pT2 in 51 patients, pT3 in 53 patients and pT4 in 20 patients. Vascular involvement and lymph node metastasis were found in 85 and 33 patients, respectively. The cause-specific 5-year survival rate was 64.2% for all patients, 74.4% for patients with grade 1 or 2 tumors, 62.9% for those with grade 3 tumors; 90.9% for those with stage pT1 or less, 77.9% for those with stage pT2, 45.0% for those with stage pT3 and 29.2% for those with stage pT4 (p < 0.001); 83.2% for patients without vascular involvement and 42.0% for those with vascular invasion (p < 0.001); and 76.5% for patients without lymph node metastasis and 22.7% for those with lymph node metastasis (p < 0.001). Multivariate analysis revealed a strong independent correlation of the pathological stage and lymph node metastasis with poor prognosis and, furthermore, the incidence of lymph node metastasis was significantly related to the increase in pathological stage. CONCLUSIONS: In this series, the pathological stage, lymph node metastasis and vascular involvement, but not tumor grade, were significantly useful prognostic factors in patients who have undergone radical cystectomy for TCC and among them only pathological stage and lymph node metastasis could be used as independent predictors for poor prognosis.

Adult↗

Significance of prostate-specific antigen--alpha(1)-antichymotrypsin complex for diagnosis and staging of prostate cancer.

OBJECTIVE: To evaluate the clinical significance of measuring the prostate-specific antigen-alpha(1)-antichymotrypsin (PSA-ACT) for differentiating prostate cancer from benign prostate hypertrophy (BPH) and for the staging of prostate cancer. METHODS: Before treatment, total PSA (tPSA) and PSA-ACT were measured in 120 patients with prostate cancer and in 150 patients with BPH using immunofluorometric techniques with different monoclonal antibodies against PSA and ACT. Furthermore, the tPSA and PSA-ACT densities of the whole prostate (PSAD and ACTD, respectively) were calculated. RESULTS: tPSA, PSAD, PSA-ACT and ACTD levels in patients with prostate cancer paralleled the clinical stage and were significantly higher than those in patients with BPH. Furthermore, these four values were significantly higher in patients with pathologically extraprostatic disease than those with organ-confined disease. Receiver operating characteristics analysis among patients with PSA values of 4.1-10 ng/ml revealed that the areas under the curve for tPSA and ACTD were similar to those for PSA-ACT and ACTD, respectively and that no significant differences in the differentiation between prostate cancer and BPH were observed among these parameters. CONCLUSIONS: Measurement of PSA-ACT provides useful information for the clinical staging of prostate cancer and differential diagnosis between prostate cancer and BPH; however, compared with tPSA, PSA-ACT may not be significantly superior in the diagnosis and staging of prostate cancer.

Diagnosis, Differential↗

Sudden death caused by tension pneumothorax after rupture of a thoracic aortic aneurysm. Case report.

A rare case of fatal tension pneumothorax is reported. An aged Japanese man with marked subcutaneous emphysema of the neck was found collapsed in a betting office. He was ascertained to have left tension pneumothorax, based on radiographic examinations carried out before his death. At autopsy, severe pneumomediastinum was observed, and the descending thoracic aorta with a ruptured dissecting aneurysm was closely adhered to the left lung pleura. The hemorrhage spread into the pulmonary parenchyma and finally spouted out from the surface of the lung apex. Because the blood loss itself was not fatal in quantity, it is concluded that the patient died of tension pneumothorax caused by a lung penetration from the rupture of an aortic aneurysm.

Aged↗

Nicorandil enhances cardiac endothelial nitric oxide synthase expression via activation of adenosine triphosphate-sensitive K channel in rat.

In the heart, nitric oxide activates an adenosine triphosphate (ATP)-sensitive K (K(ATP)) channel that is constructed of two subunits, i.e., an ATP-binding cassette protein sulfonylurea receptor (SUR2) and a pore-forming inward rectifier (Kir6.1 or 6.2). However, whether this K(ATP) channel affects nitric oxide activation is unknown. Our aim was to assess whether pharmacologic activation of the K(ATP) channel by nicorandil contributes to endothelial nitric oxide synthase (eNOS) levels. A total of 21 7-week old male Sprague-Dawley rats were used. Seven were treated by intraperitoneal injection of nicorandil at 3 mg/kg/d; seven were treated with intraperitoneal nicorandil at 3 mg/kg/d after glibenclamide at 12 mg/kg/d twice a day p.o.; and seven were left untreated (controls). At 24 h after treatment, blood pressure and heart rate were measured, and eNOS, SUR2, Kir6.1, and Kir6.2 mRNA levels and eNOS protein levels in the left ventricle were determined by reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis. Nicorandil caused tachycardia without a change in blood pressure, whereas glibenclamide had no effect on the nicorandil-induced change in heart rate or on blood pressure. RT-PCR revealed that nicorandil increased the eNOS and SUR2 mRNA levels by 2.2- and 2.0-fold, respectively, (p < 0.01 versus control), and that these increases were completely inhibited by glibenclamide. A significant correlation was observed between eNOS and SUR2 mRNA levels in all experimental rats (r = 0.760, p < 0.001). However, Kir6.1 or 6.2 mRNA level was constant. Western blot analysis revealed that nicorandil caused a 1.6-fold increase in eNOS protein levels (p < 0.01 versus control). This increase was completely inhibited by glibenclamide. In conclusion, up-regulation of eNOS mRNA and protein levels by nicorandil, and inhibition of this upregulation by glibenclamide, were demonstrated in normotensive conscious rat hearts. Nicorandil appears to enhance cardiac eNOS expression via activation of a K(ATP) channel.

ATP-Binding Cassette Transporters↗

Secreted type of modified interleukin-18 gene transduced into mouse renal cell carcinoma cells induces systemic tumor immunity.

PURPOSE: Interleukin (IL)-18 is a novel cytokine that has been identified as a strong interferon-gamma inducer. IL-18 has bioactivity similar to that of IL-12 and demonstrates antitumor effects. Since IL-18 does not have a signal sequence, we constructed the gene, consisting of the signal sequences of interferon-beta and mature IL-18 complementary (c) DNA. The modified gene was subsequently transduced into a mouse renal cell carcinoma cell line to induce IL-18 secretion from tumor cells to establish whether this IL-18 secreting tumor cell line may induce systemic tumor immunity. MATERIALS AND METHODS: Modified IL-18 cDNA consisting of the signal sequences of interferon-beta and mature type of IL-18 cDNA was constructed by the overlap extension method. The modified and original IL-18 cDNA was transduced into the RenCa mouse renal cell carcinoma cell line. Expression of IL-18 messenger RNA and concentration of IL-18 in the culture supernatant were determined. Direct antitumor and tumor vaccine effects were investigated in syngeneic Balb/c mice. To determine the mechanism of the antitumor effect immunodeficient mice were challenged with IL-18 secreting RenCa cells. RESULTS: Although the modified and original IL-18 genes transduced RenCa showed almost the same level of IL-18 messenger RNA expression, only RenCa cells transduced with modified IL-18 gene secreted IL-18 into the culture supernatant and were completely rejected when transplanted into syngeneic mice. T lymphocytes were involved in this antitumor effect. Moreover, the modified IL-18 transduced RenCa induced tumor vaccine effect against parental RenCa cells injected at a distant site. CONCLUSIONS: Immune gene therapy using modified IL-18 cDNA appears to be effective and IL-18 secreting cancer cells may be a candidate for tumor vaccine therapy.

Animals↗

5-HT2A promoter polymorphism is not associated with anorexia nervosa in Japanese patients.

Genetic factors have been implicated in playing a significant role in susceptibility to anorexia nervosa (AN). Among many candidate genes for AN, an association with the A allele of the -1438G/A polymorphism in the promoter region of the 5-HT2A receptor has been reported. However, these findings are controversial and all patients studied to date have been Caucasian. This study was designed to determine whether this association is reproducible in Japanese subjects. This case-control study of a cohort of 75 female Japanese AN sufferers and 127 normal female control subjects revealed no significant association between the 5-HT2A promoter polymorphism and AN. Thus, at least for Japanese subjects, the A-allele of the -1438G/A polymorphism in the promoter region of the 5-HT2A receptor gene does not contribute to a predisposition to AN.

Alleles↗

Analysis of tumor necrosis factor-alpha gene promoter polymorphisms in anorexia nervosa.

Elevated plasma tumor necrosis factor-alpha (TNFalpha) levels and enhanced spontaneous TNFalpha release from peripheral blood mononuclear cells in patients with anorexia nervosa (AN) have been reported. TNFalpha activates the hypothalamic-pituitary-adrenal axis and reduces food intake, which is characteristic of eating disorders. Recently, three novel polymorphisms in the 5'-flanking region of the TNFalpha gene were reported at positions -1031 (T --> C substitution), -863 (C --> A) and -857 (C --> T). Differences in these alleles are reportedly related to altered TNFalpha-transcriptional promoter activity. Therefore, we performed a case-control association analysis to determine whether any of those three polymorphisms in the TNFalpha promoter region were involved in a predisposition to AN. The results of our analysis of a cohort of 79 female Japanese AN sufferers and 127 normal female control subjects provide no support for the hypothesis that -1031T/C, -863 C/A and -857C/T polymorphisms in the TNFalpha gene promoter region influence the susceptibility to AN.

Adult↗

Investigation of varicella-zoster virus DNA in lymphocyte subpopulations by quantitative PCR assay.

To investigate the nature of viremia during the acute phase of varicella, we studied the viral load in nine otherwise healthy children with varicella. Plasma and peripheral blood mononuclear cells (PBMC) were obtained, then PBMC were divided into CD4+T, CD8+T, and B lymphocytes and monocyte/macrophage fractions. The viral DNA in each component was quantified using a real-time quantitative polymerase chain reaction assay. Varicella-zoster virus (VZV) DNA was detected in plasma, PBMC and all subpopulations. The amount of viral DNA was similar in each PBMC subpopulation, suggesting that each lymphocyte fraction and monocytes carry similar amounts of VZV DNA during viremia.

Animals↗

Adrenomedullin and proadrenomudullin N-terminal 20 peptide (PAMP) are present in human colonic epithelia and exert an antimicrobial effect.

The hypotensive and vasorelaxing peptides adrenomedullin (AM) and its gene-related peptide, proadrenomedullin N-terminal 20 peptide (PAMP), were found to be distributed on the surface of the colonic mucosa. AM and PAMP showed dose-dependent antimicrobial activity against E. coli. The results suggest that the novel vasoactive peptides AM and PAMP play an important role in mucosal defence.

Adrenomedullin↗