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Biomedical subjects

S Mukai

Publications and source records attributed to S Mukai.

At least 19 recordsLinked to original sources
PubMed1995

Expression of cyclooxygenase-1 and -2 in human colorectal cancer.

Several studies indicate that nonsteroidal anti-inflammatory drugs including indomethacin, aspirin, sulindac, and piroxicam reduce the risk of colon cancer. Furthermore, nonsteroidal anti-inflammatory drugs that inhibit the cyclooxygenase (COX) enzyme were shown to inhibit the development of colon cancer in animal models of carcinogenesis. Non-steroidal anti-inflammatory drugs inhibit the enzymatic activity of both the constitutive (COX-1) and inducible (COX-2) isoforms of COX enzyme. We have investigated the expression of COX-1 and COX-2 polypeptides in human colon cancer tissues using immunohistochemistry. Enhanced COX-2 expression was observed in colon cancer tissues from 15 subjects with clinically diagnosed colorectal cancer. Marked COX-2 expression was observed in cancer cells, inflammatory cells, vascular endothelium, and fibroblasts of the lesional tissues compared with the nonlesional and normal colon tissues. The extent and intensity of the immunoreactive COX-2 in cancer cells was much greater than that of the other cell types. In contrast, the expression of COX-1 polypeptide was weak in both normal and cancerous specimens. These data suggest that the enhanced expression of the COX-2 gene in colon cancer tissues may contribute to the enhanced synthesis of prostaglandin E2 by the colon cancer tissues. Enhanced expression of COX-2 may play a role in the pathogenesis of colon cancer. Furthermore, selective inhibition of COX-2 may prove to be more efficacious in the retardation of colon cancer development.

Adenocarcinoma↗
PubMed1995

Corticotropin releasing hormone in colonic mucosa in patients with ulcerative colitis.

Corticotropin releasing hormone (CRH) is a key hormone in integrated response to stress, acting as the major regulator of the hypothalamic-pituitary-adrenal axis. Recently, local production of CRH has been detected in normal human colonic enterochromaffin cells. CRH is locally secreted in granulomatous and arthritic tissues in rats and humans, where it seems to act as a local proinflammatory agent. To find out if CRH is present in colonic tissues of patients with ulcerative colitis, this study examined the expression of this peptide in the large bowel of patients with ulcerative colitis. Colonic tissues of patients with ulcerative colitis obtained by endoscopic biopsy were immunostained with anti-CRH antibody. CRH messenger (m) RNA was also examined in biopsy specimens of ulcerative colitis by the reverse transcribed polymerase chain reaction method and by in situ hybridisation. Considerably enhanced expression of immunoreactive CRH was found in mucosal inflammatory cells. Intense staining with anti-CRH antibody was also shown in mucosal macrophages. CRH mRNA was expressed in mucosal epithelial cells. The expression of immunoreactive CRH in colonic mucosal epithelial cells of ulcerative colitis slightly increased, but not significantly, compared with normal colonic mucosal epithelial cells. These results suggest that CRH may play a part in the modulation of intestinal immune and inflammatory system, and as a modulator in the pathogenesis of ulcerative colitis.

Adult↗
PubMed1995

Heart rate and blood pressure variabilities during graded head-up tilt.

We investigated the responses of the frequency components of heart rate (HR) and blood pressure (BP) variabilities to progressive changes in autonomic activity induced by the graded head-up tilt technique in 12 normal subjects (age 19-27 yr) under the condition of frequency-controlled respiration (0.25 Hz). During low-level tilt (0-30 degrees), the R-R interval was unchanged and the amplitude of the high-frequency (HF; 0.25 Hz) component of HR variability showed only a slight insignificant decrease. The amplitude of the low-frequency (LF; 0.04-0.15 Hz) component of HR variability increased progressively as the angle increased (P < 0.05). During high-level tilt (30-90 degrees), the R-R interval and the HF amplitude of HR variability decreased progressively with tilt angle (P < 0.001 for both). The LF amplitude of HR variability peaked at a tilt angle of 30 degrees. The LF-to-HF ratio of HR variability and the LF amplitude of systolic and diastolic BP variabilities increased progressively as the tilt angle increased from 0 to 60 degrees (P < 0.001), although systolic and diastolic BPs were unchanged. These results suggest that mixed autonomic responses to orthostatic stress, which are thought to be mediated by both cardiopulmonary and arterial baroreflex mechanisms, can be distinguished by changes in the frequency components of HR and BP variabilities.

Adult↗
PubMed1995

Clinical effectiveness of lansoprazole in patients with gastric ulcers: evaluation of quality of ulcer healing based on endoscopic ultrasonographic findings.

The effects of lansoprazole (30 mg/day) in 18 patients with gastric ulcers and the quality of ulcer healing were studied using endoscopy (including dye endoscopy) and endoscopic ultrasonography (EUS). The results showed an 8-week endoscopic healing rate of 94.4% and an S2-stage shift rate of 11.1%. In dye endoscopic findings of 11 S1-stage patients, S1b healing with regenerated mucosa close to S2 was seen in 63.6%. In a study of EUS findings, E0 with few relapses and high quality of healing accounted for 44.4%. When E0 rates were compared with the scarring images seen in endoscopic findings, the rates were 100% for S2, 66.7% for S1b, and 33.3% for S1a. These results indicate that a high degree of ulcer healing was achieved with lansoprazole, as good contraction of the ulcer tissue and early maturation of regenerated epithelium were observed.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1995

[Complications of endocardial biopsy in heart transplant patients].

Despite the increasing use of alternative techniques, endomyocardial biopsy remains the primary method for diagnosing cardiac allograft rejection. Between March 1986 and May 1994, 2,894 endomyocardial biopsies performed on 183 heart transplant patients were reviewed. A total of 53 (1.8%) complications occurred. 33 (1.1%) complications were associated with the introduction, including carotid puncture (0.9%), neurological reaction (0.1%), and pneumothorax (0.1%). Complications during biopsy included arrhythmias (0.4%) and ventricular perforation (0.2%). In addition, we observed three episodes of allergic reaction to a reusable biotome, three episodes of liver biopsy, and one case of pacemaker dislodgement. All complications were without significant long-term sequelae. In contrast to the cardiomyopathy population, no severe ventricular perforations or deaths occurred. Thus although endomyocardial biopsy has some risk, it continues to be a safe and effective way of monitoring rejection.

Adolescent↗
PubMed1995

[The effectiveness of perfluorotributylamine/pluronic F-68 stem-emulsion (FC43se) against xenograft rejection in the guinea pig-to-rat model].

The administration of perfluorotributylamine/pluronic F-68 stem-emulsion (FC43se), a fluorine compound emulsion, to a rodent discordant xeno-transplantation (dXT) model led to the discovery of the inhibitory effect of this compound against hyperacute rejection (HAR). When a guinea pig heart was transplanted to a rat administered with FC43se (10 microliters/g body weight), rhythmic beating was maintained for 1110 +/- 111.1 min (mean +/- SD; n = 8) whereas the untreated heart continued to beat for 15.5 +/- 6.6 min (mean +/- SD; n = 8). After 720 min of re-beating; pathologic changes observed in the untreated group, such as multiple thrombosis in the coronary vessels, were not observed in the FC43se-administered group by light and electron microscopic examination, and endothelial cells were well preserved. On the other hand, scattered necroses of the myocardium were observed and lymphocytic infiltration was demonstrated in the interstitium. We concluded that FC43se possessed a HAR inhibitory effect by inhibiting thrombus formation in the xeno-graft heart. Using this model, we speculated that action in the vessels of the graft heart (intravascular HAR) caused thrombus formation in the vessels. On the other hand, extravascular HAR causes myocardial necrosis more slowly, not resulting in cardiac arrest in the short term.

Acute Disease↗
PubMed1994

Association and chance occurrence of aniridia and retinoblastoma.

PURPOSE/METHODS: A 9-month-old infant had inherited aniridia and unilateral retinoblastoma. Family history disclosed three generations of aniridia; yet there were no instances of retinoblastoma. The coincidental occurrence of retinoblastoma and aniridia is rare. RESULTS/CONCLUSIONS: With DNA probes from within the retinoblastoma gene, we were able to determine that a retinoblastoma-predisposing mutation was not inherited with aniridia in this family. The occurrence of these two diseases in the same individual therefore represents a chance event.

Aniridia↗
PubMed1994

Local secretion of corticotropin-releasing hormone by enterochromaffin cells in human colon.

BACKGROUND/AIMS: Corticotropin-releasing hormone (CRH) is a regulator of the hypothalamic-pituitary-adrenal axis and a coordinator of the gastrointestinal response to stress. In addition to its central effects, CRH has peripheral effects on the immune system. CRH is present in several human tissues, such as the brain, spinal cord, adrenal medulla, lung, liver, peripheral blood leukocytes, as well as the gastrointestinal tract. The current study examined the local production of CRH in the normal human colon. METHODS: Normal human colonic tissues obtained by endoscopic biopsy were immunostained with anti-CRH and anti-5-hydroxytryptamine antibody and analyzed for CRH messenger (m)RNA by a reverse-transcribed polymerase chain reaction method and by in situ hybridization. RESULTS: Immunoreactive CRH and CRH mRNA were detected in the colonic mucosal cells in the neighborhood of the base of the crypts. The mucosal cells that expressed CRH mRNA also immunostained with anti-5-hydroxytryptamine antibody. CONCLUSIONS: Normal human colonic mucosal enterochromaffin cells produce CRH. CRH in the colonic mucosa may play a role in the modulation of the intestinal immune system and/or other gastrointestinal functions basally during stressful conditions.

Adolescent↗
PubMed1994

Recombinant human granulocyte colony-stimulating factor augments cytotoxicity of OK-432-induced polymorphonuclear leukocytes.

Polymorphonuclear leukocytes (PMNs) recovered from the peritoneal cavity of mice treated with the streptococcal preparation OK-432, exhibited strong cytotoxicity after the in vitro addition of Nocardia rubra cell wall skeleton (N-CWS). In this study, we investigated whether recombinant human granulocyte colony-stimulating factor (rhG-CSF) could augment the cytotoxicity of OK-432-induced PMNs after the addition of N-CWS in vitro. PMNs recovered from the peritoneal cavity of 8- to 10-week-old, male C3H/He mice induced by intraperitoneal (i.p.) injection of 50 KE/kg (1 KE = 0.1 mg) of OK-432 were used in a 51Cr release assay against MM46 mammary carcinoma cells. While addition of rhG-CSF in vitro did not augment the cytotoxicity of OK-432-induced PMNs, marked augmentation of the cytotoxicity of OK-432-induced PMNs was observed following a single subcutaneous (s.c.) or i.p. injection of 125 micrograms/kg of rhG-CSF. The effect of in vivo administered rhG-CSF was dependent on the timing of the injection with respect to OK-432 administration and differed from s.c. or i.p. injections. Interestingly, the cytotoxicity of OK-432-induced PMNs was rather weak following consecutive s.c. or i.p. administration of rhG-CSF for 7-14 days. H2O2 is likely involved in mediating the cytotoxicity of OK-432-induced PMNs since activity was significantly reduced by the in vitro addition of low concentration of catalase. Generation of H2O2 by the PMNs correlated with cytotoxicity. These results suggest that in vivo administration of rhG-CSF augments the cytotoxicity of OK-432-induced PMNs in a time dependent fashion and that H2O2 plays an important role in mediating their cytotoxicity.

Animals↗
PubMed1994

Cooperative tumorigenic effects of germline mutations in Rb and p53.

The tumour suppressor genes Rb and p53 are mutated in several types of human cancer, and many tumour types carry mutations in both genes. To study how these genes normally function, we and others have created mouse strains with Rb and p53 mutations. Here we describe the phenotypic effects of combined germline mutations in these two tumour suppressor genes. Mice mutant for both genes have reduced viability and exhibit novel pathology including pinealoblastomas, islet cell tumours, bronchial epithelial hyperplasia and retinal dysplasia. These data indicate that mutations in Rb and p53 can cooperate in the transformation of certain cell types in the mouse.

Adenoma, Islet Cell↗
PubMed1994

Effects of respiratory interval on vagal modulation of heart rate.

To determine whether paced breathing (PB) and respiratory interval of PB modify the relationship between spectral components of heart rate variability (HRV) and cardiac vagal tone, we studied seven healthy young males under the condition of beta-adrenergic blockade by intravenous propranolol (0.2 mg/kg). Compared with spontaneous breathing, PB at the same respiratory interval as that of individual spontaneous breathing showed no significant effect on the amplitude of the high-frequency (HF) component or the mean R-R interval in either the supine or tilt position, whereas the PB decreased the amplitude of the low-frequency (LF; 0.04-0.15 Hz) component in both positions (P = 0.004 and 0.042, respectively). When the respiratory interval was increased from 3 to 6 s, the HF amplitude showed a progressive increase in both positions (P = 0.001 and 0.035, respectively), while the LF amplitude and mean R-R interval remained unchanged. These results indicate that the effects of PB and respiratory interval on the spectral components of HRV are not mediated by the changes in mean cardiac vagal tone and support the hypothesis that increased respiratory interval amplifies the respiratory-related vagal modulation of heart rate.

Adrenergic beta-Antagonists↗
PubMed1994

Assessment of frequency shifts in R-R interval variability and respiration with complex demodulation.

A complex demodulation (CDM) method for continuous assessment of frequency shifts and time-dependent changes in amplitude in the rhythmic components existing in predefined frequency bands was proposed and applied to the analysis of high-frequency (HF) and low-frequency (LF) components of the R-R interval and to the analysis of respiration via impedance spirogram. Simulation studies revealed that this CDM technique furnishes mathematical features well suited to the investigation of non-stationary R-R interval signals and can delineate time-dependent fluctuations in both amplitude and frequency, accurately differentiating between HF and LF components. Analysis of data during paced breathing at different respiratory frequencies revealed that the estimated frequency of the HF component and respiration faithfully reflected the frequency of paced breathing. Analysis of data during dynamic exercise with increasing workload (20 W/min) showed that the frequency of the HF component was elevated with exercise and that both HF and LF amplitudes were reduced progressively with advancing load. CDM-derived frequency and amplitude of respiration were highly correlated to direct breath-by-breath respiratory frequency and tidal volume measurements. We conclude that this method could provide a powerful means for continuously assessing time-dependent changes in both cardiovascular and respiratory variations.

Adult↗
PubMed1994

Rupture of donor ascending aorta following heart transplantation.

Among 81 patients who underwent orthotopic heart transplantation between July 1986 and December 1990, we found rupture of the donor ascending aorta in three patients, all with severe ventricular dysfunction secondary to aortic valvular disease. The mechanism for this may be compliance mismatch between the recipient ascending aorta and the donor ascending aorta. This situation is a unique complication in heart transplantation for the recipients who have severe athero-sclerotic changes in the systemic aortic wall, especially for those with valvular diseases caused by calcification.

Aortic Rupture↗