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Biomedical subjects

Y Koyama

Publications and source records attributed to Y Koyama.

At least 145 records · Page 8Linked to original sources

Suicide risk among cancer patients: experience at one medical center in Japan, 1978-1994.

In order to identify the risks, methods and locations of suicide among Japanese cancer patients, we followed up 23,979 cancer patients aged 15 years and older, who were newly diagnosed at one medical center between 1978-94. Suicide risk was evaluated by comparing the observed number (O) with the expected number (E), which was calculated from the suicide mortality rate among Osaka residents. By the end of 1994, there were 48 suicide death among 109,374 person-years of follow-up. Suicide risk was significantly increased within the first five years following cancer diagnosis (male: O/E=1.62, 95% confidence interval (CI)=1.03-2.43, female: O/E=2.13, 95% CI=1.22-3.47), and decreased to unity after five years had elapsed following the cancer diagnosis. Patients in their fifties (O/E=1.93, 95% CI=1.48-4.37), diagnosed between 1978-85 (O/E=1.93, 95% CI=1.19-2.95), having remote metastasis at their initial diagnosis (O/E=4.66, 95% CI=2.12-8.84), the site being in the female genital organs (O/E=3.58, 95% CI=1.54-7.06) or in the male genital organs (O/E= 5.86, 95% CI=1.58-15.05), had a significantly higher suicide risk within five years following cancer diagnosis. The highest suicide mortality was observed between the third and fifth months after cancer diagnosis (O/E=4.35, 95% CI=1.87-8.58); most of these suicides (7/8) occurred soon after discharge from hospital. Among the 39 patients who committed suicide within five years after their diagnosis, the most common method among those who took their lives while in hospital was by jumping to their death (10/16), and that among those who committed suicide in other locations was by hanging (14/23). These findings indicate that Japanese patients with cancer run the highest risk of suicide soon after having been discharged from hospital. Clinicians should assess cancer patients' psychological distress and potential risk of suicide before approving discharge from hospital.

Adolescent↗

Cytomegalovirus IE2 protein stimulates interleukin 1beta gene transcription via tethering to Spi-1/PU.1.

Potent induction of the gene coding for human prointerleukin 1beta (il1b) normally requires a far-upstream inducible enhancer in addition to a minimal promoter located between positions -131 and +12. The transcription factor Spi-1 (also called PU.1) is necessary for expression and binds to the minimal promoter, thus providing an essential transcription activation domain (TAD). In contrast, infection by human cytomegalovirus (HCMV) can strongly activate il1b via the expression of immediate early (IE) viral proteins and eliminates the requirement for the upstream enhancer. Spi-1 has been circumstantially implicated as a host factor in this process. We report here the molecular basis for the direct involvement of Spi-1 in HCMV activation of il1b. Transfection of Spi-1-deficient HeLa cells demonstrated both the requirement of Spi-1 for IE activity and the need for a shorter promoter (-59 to +12) than that required in the absence of IE proteins. Furthermore, in contrast to normal, enhancer-dependent il1b expression, which absolutely requires both the Spi-1 winged helix-turn-helix (wHTH) DNA-binding domain and the majority of the Spi-1 TAD, il1b expression in the presence of IE proteins does not require the Spi-1 TAD, which plays a synergistic role. In addition, we demonstrate that a single IE protein, IE2, is critical for the induction of il1b. Protein-protein interaction experiments revealed that the wing motif within the Spi-1 wHTH domain directly recruits IE2. In turn, IE2 physically associates with the Spi-1 wing and requires the integrity of at least one region of IE2. Functional analysis demonstrates that both this region and a carboxy-terminal acidic TAD are required for IE2 function. Therefore, we propose a protein-tethered transactivation mechanism in which the il1b promoter-bound Spi-1 wHTH tethers IE2, which provides a TAD, resulting in the transactivation of il1b.

Binding Sites↗

Expression and localization of aquaporins in rat gastrointestinal tract.

A family of water-selective channels, aquaporins (AQP), has been demonstrated in various organs and tissues. However, the localization and expression of the AQP family members in the gastrointestinal tract have not been entirely elucidated. This study aimed to demonstrate the expression and distribution of several types of the AQP family and to speculate on their role in water transport in the rat gastrointestinal tract. By RNase protection assay, expression of AQP1-5 and AQP8 was examined in various portions through the gastrointestinal tract. AQP1 and AQP3 mRNAs were diffusely expressed from esophagus to colon, and their expression was relatively intense in the small intestine and colon. In contrast, AQP4 mRNA was selectively expressed in the stomach and small intestine and AQP8 mRNA in the jejunum and colon. Immunohistochemistry and in situ hybridization demonstrated cellular localization of these AQP in these portions. AQP1 was localized on endothelial cells of lymphatic vessels in the submucosa and lamina propria throughout the gastrointestinal tract. AQP3 was detected on the circumferential plasma membranes of stratified squamous epithelial cells in the esophagus and basolateral membranes of cardiac gland epithelia in the lower stomach and of surface columnar epithelia in the colon. However, AQP3 was not apparently detected in the small intestine. AQP4 was present on the basolateral membrane of the parietal cells in the lower stomach and selectively in the basolateral membranes of deep intestinal gland cells in the small intestine. AQP8 mRNA expression was demonstrated in the absorptive columnar epithelial cells of the jejunum and colon by in situ hybridization. These findings may indicate that water crosses the epithelial layer through these water channels, suggesting a possible role of the transcellular route for water intake or outlet in the gastrointestinal tract.

Animals↗

Role of a negative arterial-portal venous glucose gradient in the postexercise state.

UNLABELLED: Prior exercise stimulates muscle and liver glucose uptake. A negative arterial-portal venous glucose gradient (a-pv grad) stimulates resting net hepatic glucose uptake (NHGU) but reduces muscle glucose uptake. This study investigates the effects of a negative a-pv grad during glucose administration after exercise in dogs. EXPERIMENTAL PROTOCOL: exercise (-180 to -30 min), transition (-30 to -20 min), basal period (-20 to 0 min), and experimental period (0 to 100 min). In the experimental period, 130 mg/dl arterial hyperglycemia was induced via vena cava (Pe, n = 6) or portal vein (Po, n = 6) glucose infusions. Insulin and glucagon were replaced at fourfold basal and basal rates. During the experimental period, the a-pv grad (mg/dl) was 3 +/- 1 in Pe and -10 +/- 2 in Po. Arterial insulin and glucagon were similar in the two groups. In Pe, net hepatic glucose balance (mg x kg(-1) x min(-1), negative = uptake) was 4.2 +/- 0.3 (basal period) and -1.2 +/- 0.3 (glucose infusion); in Po it was 4.1 +/- 0.5 and -3.2 +/- 0.4, respectively (P < 0.005 vs. Pe). Total glucose infusion (mg x kg(-1) x min(-1)) was 11 +/- 1 in Po and 8 +/- 1 in Pe (P < 0.05). Net hindlimb and whole body nonhepatic glucose uptakes were similar. CONCLUSIONS: the portal signal independently stimulates NHGU after exercise. Conversely, prior exercise eliminates the inhibitory effect of the portal signal on glucose uptake by nonhepatic tissues. The portal signal therefore increases whole body glucose disposal after exercise by an amount equal to the increase in NHGU.

Alanine↗

Pancreatic innervation is not essential for exercise-induced changes in glucagon and insulin or glucose kinetics.

The purpose of this study was to determine the role of pancreatic innervation in mediating exercise-induced changes in pancreatic hormone secretion and glucose kinetics. Dogs underwent surgery >16 days before an experiment, at which time flow probes were implanted on the portal vein and the hepatic artery, and Silastic catheters were inserted in the carotid artery, portal vein, and hepatic vein for sampling. In one group of dogs (DP) all nerves and plexuses to the pancreas were sectioned during surgery. A second group of dogs underwent sham denervation (SHAM). Pancreatic tissue norepinephrine was reduced by >98% in DP dogs. Each study consisted of basal (-30 to 0 min) and moderate exercise (0 to 150 min, 100 m/min, 12% grade) periods. Isotope ([3-(3)H]glucose) dilution and arteriovenous differences were used to assess hepatic function. Arterial and portal vein glucagon and insulin concentrations and the rate of net extrahepatic splanchnic glucagon release (NESGR) were similar in DP and SHAM during the basal period. Arterial and portal vein glucagon and NESGR increased similarly in DP and SHAM during exercise. Arterial and portal vein insulin were similar during exercise. Arterial glucose, tracer-determined endogenous glucose production, and net hepatic glucose output were similar in DP and SHAM during the basal and exercise periods. These results demonstrate that pancreatic nerves are not essential to pancreatic hormone secretion or glucose homeostasis during rest or moderate exercise.

Animals↗

Effect of injury to the dorsal funiculus of the thoracic spinal cord on micturition in decerebrate and freely-moving cats.

Bladder sensation is transmitted both via the spinothalamic tract in the lateral funiculus and the dorsal system in the dorsal funiculus. We transected the dorsal funiculus in 10 female cats to clarify the functional roles of these two ascending pathways. The dorsal funiculus was transected at T10 in 5 decerebrate and 5 freely-moving cats, and micturition parameters were compared before and after transection. Transection of the dorsal funiculus did not affect any of the parameters of reflex micturition in the 5 decerebrate cats. Within 1 week after transection, 4 of the 5 freely-moving cats used the normal micturition posture, but the remaining one performed micturition in a prone position as if she had lost micturition sensation. All 5 cats urinated with a normal micturition posture by 2 weeks after transection. The mean single voided volume was decreased transiently up to 1 week, but returned to normal by 2 weeks after transection. None of the 5 cats had any residual urine before and after transection. Both the ascending and descending limbs of the micturition reflex pass through the lateral funiculus. Bladder sensation is transmitted both via the spinothalamic tract coursing in the lateral funiculus and the dorsal system in the dorsal funiculus. The dorsal system may play a major role in the transmission of bladder sensation to the cerebral cortex, but may not be essential.

Animals↗

Adhesion of macrophages on collagen irradiated with ultraviolet light.

Properties of collagen irradiated with ultraviolet (UV) light were examined using the techniques of sodium dodecyl sulfate-polyacrylamide gel electrophoresis, spectroscopic measurements, and cell adhesion assay. Both photopolymerization and photodegradation of the collagen appeared to occur with UV irradiation because the aggregation of collagen and disintegration of the triple-helical structure were observed. The formation of the cross-links between the tyrosine residues in collagen by photoreaction was presumed. The adhesion of macrophages (Mphis) on a polystyrene plate was suppressed by coating the plate surface with collagen. Anti-adhesive activity of collagen on Mphi cells decreased with UV irradiation. However, appreciable anti-adhesive activity remained in the modified collagen even when collagen was irradiated with UV light for 24 h.

Biocompatible Materials↗

Angiotensin II type 2 receptor overexpression activates the vascular kinin system and causes vasodilation.

Angiotensin II (Ang II) is a potent vasopressor peptide that interacts with 2 major receptor isoforms - AT1 and AT2. Although blood pressure is increased in AT2 knockout mice, the underlying mechanisms remain undefined because of the low levels of expression of AT2 in the vasculature. Here we overexpressed AT2 in vascular smooth muscle (VSM) cells in transgenic (TG) mice. Aortic AT1 was not affected by overexpression of AT2. Chronic infusion of Ang II into AT2-TG mice completely abolished the AT1-mediated pressor effect, which was blocked by inhibitors of bradykinin type 2 receptor (icatibant) and nitric oxide (NO) synthase (L-NAME). Aortic explants from TG mice showed greatly increased cGMP production and diminished Ang II-induced vascular constriction. Removal of endothelium or treatment with icatibant and L-NAME abolished these AT2-mediated effects. AT2 blocked the amiloride-sensitive Na(+)/H(+) exchanger, promoting intracellular acidosis in VSM cells and activating kininogenases. The resulting enhancement of aortic kinin formation in TG mice was not affected by removal of endothelium. Our results suggest that AT2 in aortic VSM cells stimulates the production of bradykinin, which stimulates the NO/cGMP system in a paracrine manner to promote vasodilation. Selective stimulation of AT2 in the presence of AT1 antagonists is predicted to have a beneficial clinical effect in controlling blood pressure.

Actins↗

Kinetics of pulmonary gas exchange during and while recovering from exercise in patients after anterior myocardial infarction.

The effect of exercise intensity on gas exchange kinetics was investigated during exercise and recovery, as well as the relationship between the kinetics during exercise and recovery. Twenty-three patients with a history of anterior myocardial infarction performed low-intensity (38.7+/-8.3 W) and high-intensity (68.8+/-15.0 W) exercise for 6 min. The time constants of oxygen uptake (VO2), carbon dioxide output (VCO2) and minute ventilation (VE) were significantly prolonged during high intensity exercise compared with low-intensity exercise (61.2+/-8.6 vs 52.3+/-10.3 s, p<0.005 for the time constant of VO2). The time constant of VO2 was similar during exercise and during recovery from exercise of high (61.2+/-8.6 vs 66.2+/-12.2 s) as well as low intensity (52.3+/-10.3 vs 55.0+/-10.1 s). However, the time constants of VCO2 and heart rate were significantly shorter during recovery than during exercise. The time constants of VCO2 and VE were significantly longer than that of VO2 during both exercise and recovery. In the present study, it was found that (1) the gas exchange kinetics were influenced by the intensity of exercise; (2) the kinetics during recovery did not necessarily reflect the kinetics during exercise except for VO2; and (3) the kinetics of VCO2 and VE were delayed as compared with the VO2 kinetics. These characteristics should be taken into account when using gas exchange kinetics to estimate cardiopulmonary responses to exercise in patients with left ventricular dysfunction.

Adult↗

Mechanism of overshoot in cardiac function during recovery from submaximal exercise in man.

BACKGROUND: A sudden increase (overshoot) in the left ventricular ejection fraction during the recovery from maximal exercise has been reported in patients with coronary artery disease, but its mechanism has not been fully clarified. We investigated whether this phenomenon may occur in normal subjects, and whether it depends on the intensity of exercise. METHODS: Thirteen normal subjects (mean [+/- SD] age, 59 +/- 8 years old) performed two levels (25 W and 50 W) of mild-intensity, constant-work-rate exercise for 6 min on a cycle ergometer. Left ventricular function was monitored continuously during the recovery from exercise using a computerized cadmium telluride detector. RESULTS: An overshoot was observed in the ejection fraction during the first minute of recovery compared with the end-exercise value. The overshoot in the ejection fraction during recovery after the 50-W exercise was greater than that seen after the 25-W exercise. An overshoot phenomenon in stroke volume was also observed during the recovery from 50-W exercise. CONCLUSIONS: The overshoot in cardiac function observed during the early phase of recovery, which was caused mainly by an immediate decrease in end-systolic volume, occurred even after exercise of mild intensity. This phenomenon appears to suggest the existence of a transient mismatch between cardiac contractility and afterload reduction during the recovery from mild-intensity exercise, even in normal subjects.

Aged↗

[Fornix of vagina suspension for cystocele].

OBJECTIVE: Bladder neck hypermobility causes cystocele in middle to old elderly women. We developed an easy and useful surgical technique for cystocele. METHODS: Thirteen patients with cystocele (grade 2-4) were operated by fornix of the vagina suspension. Patients were placed on lithotomy position under general or spinal anesthesia. Lower midline or lower abdominal transverse incision was made to open the peritoneum and denuded vesicouterine pouch. Several nylon sutures were placed on the lateral side of exposed fornix of the vagina. These sutures were suspended to anterior layer of the rectus sheath. Fornix of the vagina was fixed to the rectus muscle, so the prolapsed bladder wall was pulled up in normal position. RESULTS: Operating time ranged from 15-110 minutes (average 73 minutes). Ten patients of thirteen were successful up to 2-43 months postoperatively. Cystocele recurred in three patients of thirteen. Two patients was re-operated by the same method, but one of them recurred. Two of three recurrent patients had grade 4 cystocele. CONCLUSION: Fornix of the vagina suspension for cystocele seems useful and promising because of easy procedure without serious morbidity, especially in elderly high-risk patients.

Aged↗

[Hypogonadotropic hypogonadism treated with HCG monotherapy: report of 3 cases].

We report 3 cases of hypogonadotropic hypogonadism and the effects of human chorionic gonadotropin (HCG) monotherapy on plasma testosterone levels, which were related to clinical results. The patients were males 29, 21 and 14 years old. Each received 5,000 units of HCG subcutaneously or intramuscularly twice or three times a week for 16 to 40 months. Genital effects, including an increase in testicular volume were seen in all patients after 2 or 3 months. The increase in plasma testosterone level after HCG therapy was significantly correlated with the genital effects similarly to other treatments. Moreover, spermatozoa appeared in one case.

Adolescent↗

[Aggressive diagnostic and therapeutic approach for acute coronary syndrome].

The purpose of this article is to propose an "aggressive strategy" in the treatment of patients with acute coronary syndrome (ACS), especially unstable angina. The indication and timing of emergent coronary angiography in patients with ACS remains to be validated. The results of TIMI III B trial, a randomized, controlled trial about this issue, show that an early invasive strategy reduced the average length of initial hospitalization and the incidence of rehospitalization within 6 weeks. However, the same kind of clinical trial named VANQWISH reported that no benefit was obtained from such an aggressive strategy. It is of paramount importance to note that these 2 studies were performed in the era of plain old balloon angioplasty. Now we can use many kinds of coronary stent which impart both excellent radial strength and flexibility. Recent studies have demonstrated that culprit lesions of ACS can be treated at the same success rate as those of stable effort angina. In our hospital, use of coronary stents in patients with ACS dramatically reduced the recurrence of ACS and the incidence of angiographic restenosis with the same initial procedure success rate. Since the mid-nineties, the radial artery has been used as a vascular access site of coronary intervention. The major advantage of this technique is lesser access site-related complications and increased patient comfort, which reduced hospital stay and cost. Recently it was demonstrated that ad-hoc transradial intervention can be applied in patients with unstable angina or even those with acute myocardial infarction by trained angioplasters. Thus, we would like to conclude that the best strategy in the management of ACS is to perform emergent coronary angiography from the radial artery as soon as possible after admission, and to do ad-hoc intervention using coronary stents suitable for the lesion anatomy.

Aged↗

Endothelin-induced protein tyrosine phosphorylation of cultured astrocytes: its relationship to cytoskeletal actin organization.

Endothelins (ETs) promote cytoskeletal actin reorganization of cultured astrocytes (Koyama and Baba, Neuroscience 61:1007-1016, 1994; Koyama and Baba, Glia 16:342-350, 1996). In this study, we examined the signal transduction involved in that activity of ETs. Immunoblot analysis with an anti-phosphotyrosine antibody showed that ET-3 (1 nM) increased tyrosine phosphorylation of 120 Kda and 70 Kda astrocytic proteins. The tyrosine phosphorylations of both proteins reached a maximum at 1 nM ET-3. In morphological examinations, ET-3 (1 nM) induced stress fibers, an organized F-actin structure, and focal adhesions in 0.5 mM dibutyryl cAMP (DBcAMP)-treated astrocytes within 30 min. Immunochemical staining of phosphotyrosine revealed that the newly formed focal adhesions possessed phosphotyrosine immunoreactivity. Phorbol 12-myristate 13 acetate (PMA, 100 nM), bradykinin (1 microM), angiotensin II (100 nM), and A23187 (5 microM) did not induce astrocytic stress fibers and had no obvious effects on tyrosine phosphorylation of 120 Kda and 70 Kda proteins. Tyrosine phosphorylation of astrocytic 120 Kda and 70 Kda proteins was stimulated by 1 mM sodium orthovanadate (VO4(3-)), a protein tyrosine phosphatase inhibitor. VO4(3-) promoted reorganization of stress fibers and focal adhesions in DBcAMP-treated astrocytes. Neither chelation of intra- and extracellular Ca2+ nor pre-treatment with pertussis toxin (PTX) affected the ET-induced tyrosine phosphorylation and stress fiber formation in cultured astrocytes. These results suggest a relationship between cytoskeletal actin reorganization and the tyrosine phosphorylation of astrocytic proteins by ETs.

Actins↗

[Retroperitoneal schwannoma arising from the adrenal area: a case report].

A 67-year-old woman presented with upper abdominal pain and was found to have a suprarenal tumor by ultrasonography and CT scanning. Under a diagnosis of non-functioning adrenal tumor, we made an extraperitoneal approach via a lumbar incision and removed the tumor together with the left adrenal gland. There was minimal blood loss. The resected tumor was firm and had a yellowish-white cut surface. The lesion measured 60 x 40 x 35 mm and weighed 50 g. The pathological diagnosis was benign schwannoma, mainly of the Antoni type A. This is the 27th case of benign schwannoma in the adrenal area reported in the Japanese literature.

Adrenal Gland Neoplasms↗

[Renal transplantation for patients with systemic lupus erythematosus: report of two cases].

Renal transplantation for patients with systemic lupus erythematosus (SLE) remains controversial. We performed living-tissue related renal transplantation on a 45-year-old woman with SLE and an eight-month history of hemodialysis. We also did cadaveric renal transplantation on a 41-year-old man with SLE and a 12-year history of hemodialysis. Serological tests including tests for antinuclear antibodies and complements were negative prior to surgery and throughout the course in both cases. The latter patients survived herpes-zoster virus infection in month 6 and bacterial pneumonia in month 9 after transplantation. Neither patient experienced any rejection or relapse of lupus nephritis after the procedure, and both maintained good renal allograft functions. The recurrence of lupus nephritis is reportedly extremely rare, i.e., with a possibility rate of less than 1% in transplant patients with burnt-out SLE. To the best of our knowledge, these cases are the 27th and 28th case reports of renal transplantation for SLE patients in Japanese literature.

Adult↗

[Simultaneous and metachronous pelvic bone metastases from renal cell carcinoma necessitating hemipelvectomy: report of two cases].

Two patients, one with and one without a history of nephrectomy for renal cell carcinoma, presented with lower abdominal pain. One of them, a 49-year-old man, had tumors in the right kidney and the right ischiadic bone. He underwent nephrectomy and pathologic findings showed renal cell carcinoma (tubular type, granular cell subtype, INF-gamma, G2). The other patient, a 33-year-old man with a previous history of left nephrectomy for renal cell carcinoma (tubular type, granular cell subtype, INF-alpha, G2), was found to have a large tumor in the pelvis, extending from the pubic and iliac bones to the hip joint. Both patients underwent embolization of the hypervascular mass using a vascular coil followed by hemipelvectomy under general anesthesia. The pathology reports confirmed bone metastases from renal cell carcinoma. Both patients survived surgery and their postoperative courses were uneventful without urinary or bowel incontinence. However, impaired potency was noted in the latter case. Immunotherapy with INF-alpha was resumed immediately after surgery.

Adult↗