Search PubMed⌕ Search

Biomedical subjects

T Murakami

Publications and source records attributed to T Murakami.

At least 253 records · Page 14Linked to original sources

Feasibility of daily concurrent chemoradiation therapy as nonsurgical management for esophageal cancer: our experience and theoretical background.

BACKGROUND AND OBJECTIVES: Many combination patterns of chemotherapy and radiotherapy (chemoradiation therapy; CRT) for the treatment of esophageal cancer indicate that the optimal doses of chemotherapeutic agents and of chemotherapy and radiotherapy regimens remain unclear. The feasibility and promising outcome of our newly developed definitive CRT for nonsurgical management of esophageal cancer, essentially based on the theoretical backgrounds of the radiosensitizing and biochemical modulation effects of chemotherapeutic agents, is investigated. METHODS: Six nonoperated esophageal cancer patients were treated by daily concurrent CRT, which consisted of continuous 5-fluorouracil administration with leucovorin, combined with a low dose of daily cisplatin administration before each fraction of radiation. Response to CRT and toxicities and survivals were evaluated. RESULTS: Complete and partial responses were seen in 2 patients each. Histologic examination of the biopsy specimens in the primary site showed no cancer cells in 4 patients; 1 of them survived for 31 months after CRT. The other 2 patients showed good-quality survival, having dramatic relief from dysphagia. There were no treatment-related deaths. CONCLUSIONS: The daily concurrent CRT is rational and promising and compares well with other series of definitive CRT. The CRT based on the theoretical background is feasible as a nonsurgical management option for esophageal cancer patients.

Aged↗

T2-weighted MR imaging for focal hepatic lesion detection: supplementary value of breath-hold imaging with half-Fourier single-shot fast spin-echo and multishot spin-echo echoplanar sequences.

The purpose of our study was to evaluate the supplementary value of breath-hold fat-suppressed T2-weighted magnetic resonance (MR) imaging with half-Fourier single-shot fast spin-echo (SE) or multishot SE echoplanar (EP) sequences combined with respiratory-triggered fat-suppressed fast SE T2-weighted MR imaging for detection and characterization of focal hepatic lesions. MR images in 42 patients with 82 solid, malignant and 77 nonsolid, benign lesions were analyzed. Image review was conducted on a segment-by-segment basis; in all, 333 liver segments were reviewed separately for solid and nonsolid lesions by three independent radiologists. For solid lesions, observer performance with receiver-operating-characteristic (ROC) analysis in one radiologist and specificity in another significantly improved after adding single-shot fast SE images. For nonsolid lesions, observer performance with ROC analysis in one radiologist and specificity in another significantly improved after adding single-shot fast SE images. Combining breath-hold half-Fourier single-shot fast SE imaging with respiratory-triggered fast SE imaging may be recommended for improved detection and characterization of focal hepatic lesions. J. Magn. Reson. Imaging 2000;12:444-452.

Adipose Tissue↗

Expression of perlecan proteoglycan in the infarct zone of mouse myocardial infarction.

Perlecan, a basal lamina proteoglycan, has been shown to interact with other extracellular matrix (ECM) components, especially type IV collagen, and is thus involved in ECM formation. Perlecan has also been postulated to promote growth factor-receptor interactions, including the binding of basic fibroblast growth factor (bFGF) to its receptor, and to enhance mitogenesis and angiogenesis. To test our hypothesis that perlecan is increased in the myocardial infarct zone, we examined perlecan expression after experimentally induced myocardial infarction in BALb/c mice by the methods of in situ hybridization, Northern blotting, and immunohistochemistry. In situ hybridization revealed mRNA signals for perlecan in the infarct marginal zone on day 2 and in the infarct interior zone around infarct granulation tissue on day 7. On day 14 the signals were observed at the center point of the infarct. The signals were detected in spindle-shaped mesenchymal cells (fibroblasts and myofibroblasts). Some surviving myocytes in the infarct marginal zone also showed positive signals. The sequential changes in the perlecan mRNA signal distribution paralleled those for type IV collagen mRNA. Northern blotting demonstrated increased expression of perlecan consistent with the observations of in situ hybridization. Immunopositive staining for perlecan was observed in the infarct zone around granulation tissue on day 7 and in the entire infarct zone on days 14-28. Immunostaining for bFGF was localized surrounding the infarct granulation tissue on day 7 and overlapped with perlecan immunostaining. The present results demonstrated the expression of perlecan by spindle-shaped mesenchymal cells (fibroblasts and myofibroblasts) and some surviving myocytes in the myocardial infarct, indicating the contribution of perlecan to the pathological course of myocardial infarction.

Animals↗

Angiotensin II type 1 receptor blockade abolishes specific K(ATP)channel gene expression in rats with myocardial ischemia.

The cardiac ATP-sensitive potassium (K(ATP)) channel is potentially composed of an inward rectifier potassium channel (Kir6.1 and/or Kir6.2) subunit and the cardiac type of sulfonylurea receptor (SUR2A). We reported that cardiac Kir6.1 mRNA and protein are specifically upregulated in the non-ischemic as well as the ischemic regions in rats with myocardial ischemia, suggesting that humoral and/or hemodynamic factors are responsible for this regulation. In the present study, pretreatment with TCV-116, an angiotensin (Ang) II type 1 receptor antagonist, completely inhibited the upregulation of Kir6.1 mRNA and protein expression in both regions of rat hearts subjected to 60 min of coronary artery occlusion followed by 24 h of reperfusion; whereas pretreatment with lisinopril, an Ang converting enzyme (ACE) inhibitor, partly inhibited this upregulation. Except for rats pretreated with TCV-116, Kir6.1 mRNA levels were positively correlated with those for brain natriuretic peptide (BNP), a molecular indicator of regional wall stress, in both the non-ischemic and the ischemic regions. Plasma Ang II levels were not elevated in rats with control myocardial ischemia compared with sham rats. Thus, the stress-related induction of cardiac Kir6.1 mRNA and protein expression under myocardial ischemia is inhibited by pretreatment with an AT1 antagonist, but also in part by an ACE inhibitor, suggesting that activation of local renin-angiotensin system may play a role.

Angiotensin I↗

Early surgery for active infective endocarditis.

OBJECTIVE: The timing of surgery for active infective endocarditis remains controversial. In this report, we have reviewed 26 patients who underwent surgery for active infective native-valve endocarditis between April 1992 and December 1998. PATIENTS AND METHOD: There were 19 male and 7 female patients (mean age 45 years). The aortic valve was involved in 8 patients, the mitral valve in 6 patients, tricuspid valve in 2 patients, both aortic and mitral valves in 7 patients, both aortic and tricuspid valve in 2 patients, and both mitral and tricuspid valve in one patient. The most common microorganisms were streptococcal species. Preoperative high New York Heart Association functional class (III and IV) was presented in 20 patients (77%). Progressive heart failure and the echocardiographic findings of vegetation (larger than 1 cm) were the main operative indications. Emergency or urgent surgery was required in 18 patients (70%). All patients underwent valve replacement, involving 25 mechanical prosthesis and 8 bioprosthesis. RESULTS: The operative mortality was 7.8% (n = 2). In the two patients who died, the infection had extended to the deep cardiac tissue and to the cerebral artery. The mean follow-up of the 24 survivors was 33 months (range from 6 to 82 months). There was no late death and no recurrence of infective endocarditis. CONCLUSION: In case of active infective endocarditis, early surgical intervention is recommended in patients with rapidly progressive cardiac deterioration or vegetation seen on echocardiography.

Adolescent↗

Increased in situ expression of nitric oxide synthase in human colorectal cancer.

There is growing evidence that nitric oxide (NO) has an important role in tumor growth. However, information on the expression of NO synthase (NOS) in colorectal cancers is scanty. We therefore investigated the distribution and expression of NOS in human colorectal cancers. The expression of three types of NOS, inducible (iNOS), endothelial (eNOS) and neuronal (nNOS), was examined by immunohistochemistry in 25 cases of colorectal cancer. The expression of iNOS was also investigated at the mRNA level using the reverse transcriptase polymerase chain reaction (RT-PCR) in 6 cases. Correlations were made between iNOS expression and the histopathological findings. Immunoreactive iNOS was detected in the tumor cells in 22 cases (88%) with diffuse cytoplasmic reactions. Expression of iNOS-mRNA detected by RT-PCR in three tumor tissues was over five-fold that in normal mucosa. Intensified immunoreactivity of iNOS was associated with vascular invasion. iNOS expression did not correlate with pathological staging, tumor size, lymph node metastasis, p53 expression or tumor vessel density. Immunoreactive eNOS stained more strongly in the endothelial cells of microvessels within and around the tumor than in the areas remote from the tumor. There is enhanced expression of iNOS and eNOS in human colorectal cancers, which may correlate with tumor growth and vascular invasion.

Adult↗

Chromosomal numerical aberrations of exfoliated cells in the urine detected by fluorescence in situ hybridization: clinical implication for the detection of bladder cancer.

Numerical aberrations of chromosomes 7 and 9 of exfoliated cells from the urinary tract were examined using fluorescence in situ hybridization (FISH). To minimize contamination with inflammatory, squamous and normal transitional cells all samples were stained using Giemsa's solution and clusters of transitional cells were selected for FISH analysis. Samples collected from 21 patients who had cystoscopic monitoring for bladder cancer were used in this study. Cystoscopy was positive in seven patients and five biopsy-proven transitional cell carcinomas were identified. Among the patients with cancer recurrence, numerical chromosomal aberrations were detected in four cases (sensitivity: 80%) and positive cytology in two cases. This preliminary pilot study shows FISH can be a useful tool for the detection of recurrence during a follow up of bladder cancer.

Adult↗

Bilateral choroidal metastases secondary to uterocervical carcinoma of the squamous cell type.

PURPOSE: To report a patient with bilateral choroidal metastases secondary to uterocervical carcinoma of the squamous cell type. METHODS: Case report. RESULTS: A 55-year-old woman complained of visual field loss and decreasing vision. Seven months earlier, uterocervical carcinoma of the squamous cell type was diagnosed and treated with chemotherapy and irradiation. Serous retinal detachment and choroidal masses were present in both eyes. Retinal detachment was lessened in both eyes after radiotherapy. The patient died of respiratory insufficiency 3 months after the appearance of choroidal metastases. At autopsy, there was no second cancer to cause the choroidal metastases. Tumor embolization was present in the choriocapillaries. CONCLUSION: Choroidal metastasis may develop from hematogenous spread of uterocervical squamous cell carcinoma.

Carcinoma, Squamous Cell↗

Impaired distensibility of neoaorta after arterial switch procedure.

BACKGROUND: Although the arterial switch operation has become the standard surgical procedure for treatment of complete transposition, postoperative problems have not been fully appreciated. One such problem may be the postoperative function of great arteries that are manipulated radically. METHODS: The diameters at four levels of the aorta were measured in 36 patients who had undergone arterial switch operation and the distensibilities were calculated. The data were compared with that of age-matched controls. RESULTS: At the level of the Valsalva sinus, aortic diameters after one-staged and two-staged operations were 137.0% +/- 21.3%N and 152.4% +/- 17.7%N of the normal aorta, respectively. The distensibilities at the Valsalva sinus in patients after one-staged and two-staged operations were 1.2 +/- 0.7 and 1.5 +/- 0.8 cm2 x dyn(-1) x 10(-6), and at the supraaortic ridge were 2.5 +/- 1.5 and 1.9 +/- 1.5 cm2 x dyn(-1) x 10(-6), respectively. CONCLUSIONS: In patients after arterial switch procedure, the distensibility of the base of aorta is decreased. Long-term follow-up is necessary to clarify the influence of the "stiffness" of the base of aorta.

Aortography↗

Induction of endometrial cycles and ovulation in a woman with combined 17alpha-hydroxylase/17,20-lyase deficiency due to compound heterozygous mutations on the p45017alpha gene.

OBJECTIVE: To describe the case of a Japanese woman with combined 17alpha-hydroxylase/17,20-lyase deficiency (congenital adrenal hyperplasia type V) and to discuss possible therapeutic procedures in such patients. DESIGN: Case report. SETTING: University hospital. PATIENT(S): A 26-year-old woman with secondary amenorrhea and primary sterility. INTERVENTION(S): Nucleotide sequencing of the P45017alpha gene (CYP17), induction of endometrial maturation with steroid hormone replacement, and ovulation induction with gonadotropin. MAIN OUTCOME MEASURE(S): Nucleotide sequence of CYP17, endometrial thickness and follicle diameter measured by transvaginal ultrasonography, and histologic evaluation of the endometrium. RESULT(S): Two different mutations were detected on CYP17: One was a deletion of the phenylalanine codon (TTC) at either amino acid 53 or 54 in exon 1, and the other was a missense mutation with the substitution of histidine (CAC) by leucine (CTC) at position 373 in exon 6. Repeated histologic evaluations performed during treatment with P consistently revealed an unripe endometrium with glands of the early secretory phase and markedly scanty stroma. Ultrasound examination revealed follicular growth and ovulation after gonadotropin administration, but insufficient thickness of the endometrium. CONCLUSION(S): Ovulation induction was possible in this patient with 17alpha-hydroxylase/17,20-lyase deficiency, but the endometrial response to steroid hormone replacement was extremely poor.

Adrenal Hyperplasia, Congenital↗

Characterization of messenger RNA expression of estrogen receptor-alpha and -beta in patients with ovarian endometriosis.

OBJECTIVE: To evaluate the expression of estrogen receptor (ER)-alpha and ER-beta messenger RNA (mRNA) in ovarian endometriosis. DESIGN: Prospective study. SETTING: University hospital. PATIENT(S): Patients with endometriosis and patients with uterine leiomyoma or carcinoma in situ. INTERVENTION(S): A sample of ovarian endometriotic cyst tissue was obtained from each of the 32 patients during laparoscopic cystectomy. Samples of ovarian tissue and endometrium were obtained from 15 patients during or just after surgery. MAIN OUTCOME MEASURE(S): Expression of mRNA for ER-alpha and ER-beta with use of the reverse transcription-polymerase chain reaction (RT-PCR) and nonradioactive in situ hybridization (ISH) techniques. RESULT(S): Expression of mRNA for ER-alpha and ER-beta was observed in all of the control tissues from the normal endometrium and normal ovaries in the RT-PCR and ISH analyses, although the distribution of positive signals changed in the ISH analysis during different phases of the menstrual cycle. Messenger RNA for ER-alpha was detected in all of the ovarian endometriotic cysts analyzed (19 of 19), but mRNA for the ER-beta was limited (12 of 19) in the RT-PCR analysis. The ISH analysis confirmed the RT-PCR results and revealed that the two estrogen receptors were localized in both epithelial and stromal cells of endometriotic tissues. CONCLUSION(S): The results suggest that predominant expression of ER-alpha in both glandular epithelial and stromal cells may be essential to the development and growth of ovarian endometriosis.

Adult↗

Quantitative analysis of estrogen receptor alpha and beta messenger ribonucleic acid levels in normal endometrium and ovarian endometriotic cysts using a real-time reverse transcription-polymerase chain reaction assay.

OBJECTIVE: To quantify messenger RNA (mRNA) levels of the two estrogen receptor isoforms, estrogen receptor-alpha (ER-alpha) and estrogen receptor-beta (ER-beta) in the eutopic endometrium and ovarian endometriotic cysts. DESIGN: Prospective study. SETTING: University hospital. PATIENT(S): Patients with endometriosis and patients with uterine leiomyoma or carcinoma in situ. INTERVENTION(S): Gonadotropin-releasing hormone agonist (GnRH-a)-treated (n = 12) or untreated (n = 24) endometriotic cysts were obtained from 36 patients during laparoscopic cystectomy. Eutopic endometrium tissues were obtained from 24 patients during or immediately after surgery. MAIN OUTCOME MEASURE(S): ER-alpha and ER-beta mRNA levels, using a real-time reverse transcription (RT)-polymerase chain reaction (PCR) assay, TaqMan RT-PCR. RESULT(S): Eutopic endometrium and ovarian endometriotic cysts showed predominantly higher levels of ER-alpha mRNA than ER-beta mRNA. Although ER-alpha and ER-beta mRNA levels in the eutopic endometrium were affected by a cyclic change in ovarian hormones, ovarian endometriotic cysts were less affected. Moreover, a long-term hypoestrogenic state induced by GnRH-a especially decreased ER-alpha mRNA levels in endometriotic cysts. Consequently, the relative ratios of ER-alpha to ER-beta mRNA levels in both GnRH-a-treated and untreated endometriotic cysts were significantly lower than those in the eutopic endometrium. CONCLUSION(S): The results suggest that the principal and regulatory effects of estrogens may be mediated mainly via ER-alpha rather than ER-beta in both the eutopic endometrium and endometriotic cysts.

Adult↗

Effect of cisplatin on H+ transport by H+ -ATPase and Na+/H+ exchanger in rat renal brush-border membrane.

The effect of the potent anticancer drug cisplatin, cis-diamminedichloroplatinum (II) (CDDP), on H+ -ATPase and Na+/H+ exchanger in rat renal brush-border membrane was examined. To measure H+ transport by vacuolar H+ -ATPase in renal brush-border membrane vesicles, we employed a detergent-dilution procedure, which can reorientate the catalytic domain of H+ -ATPase from an inward-facing configuration to outward-facing one. ATP-driven H+ pump activity decreased markedly in brush-border membrane prepared from rats two days after CDDP administration (5 mg/kg, i.p.). In addition, N-ethylmaleimide and bafilomycin A1 (inhibitors of vacuolar H+ -ATPase)-sensitive ATPase activity also decreased in these rats. The decrease in ATP-driven H+ pump activity was observed even at day 7 after the administration of CDDP. Suppression of ATP-driven H+ pump activity was also observed when brush-border membrane vesicles prepared from normal rats were pretreated with CDDP in vitro. In contrast with H+ -ATPase, the activity of Na+/H+ exchanger, which was determined by measuring acridine orange fluorescence quenching, was not affected by the administration of CDDP. These results provide new insights into CDDP-induced renal tubular dysfunctions, especially such as proximal tubular acidosis and proteinuria.

Adenosine Triphosphate↗

JTT-501, a new oral hypoglycemic agent, reverses hypertriglyceridemia in Zucker fatty and ventromedial hypothalamus-lesioned obese rats.

JTT-501 is a new oral hypoglycemic agent that is reported to be effective in insulin-resistant diabetic animal models by improving insulin resistance. It also improves hypertriglyceridemia. We investigated the mechanism of the reversal of hypertriglyceridemia in two types of obese animals using JTT-501. In Zucker fatty obese rats, an animal model of genetic obesity, fasting plasma triglyceride and glucose significantly decreased after a single daily oral dose of JTT-501 (100 mg/kg) for 7 days. In ventromedial hypothalamus (VMH)-lesioned obese rats, an animal model of nongenetic obesity, fasting plasma triglycerides significantly decreased but fasting plasma glucose levels remained unchanged after treatment with this agent. In Sprague-Dawley (SD) rats, fasting plasma triglyceride and glucose levels remained unchanged. The JTT-501-treated Zucker fatty and VMH-lesioned obese rats showed a decrease in insulin, but it was not significant, while the treated SD rats showed a significant decrease in insulin. Postheparin plasma lipoprotein lipase (LPL) increased significantly in treated Zucker fatty obese and SD rats, but did not change in VMH-lesioned obese rats. The hepatic triglyceride secretion rate (TGSR) did not change in any species treated with JTT-501. There was a negative correlation between postheparin plasma LPL and plasma triglyceride levels in Zucker fatty obese rats, while no such correlation was observed in VMH-lesioned obese or SD rats. The fractional catabolic rate (FCR) for plasma triglyceride was increased significantly by JTT-501 in both Zucker fatty and VMH-lesioned obese rats. These results suggest that JTT-501 decreases plasma triglycerides mainly by increasing postheparin plasma LPL in Zucker fatty obese rats, while it ameliorates an impairment in the ability of adipose tissue to remove triglyceride from the circulation in VMH-lesioned obese rats.

Animals↗