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Biomedical subjects

H Kuroda

Publications and source records attributed to H Kuroda.

At least 145 records · Page 8Linked to original sources

Ursodeoxycholic acid inhibits the induction of nitric oxide synthase.

Ursodeoxycholic acid was recently recognized as an effective agent in the treatment of primary biliary cirrhosis. Since the beneficial effect of ursodeoxycholic acid therapy appears to be mediated in part by an immune mechanism, we evaluated the effects of ursodeoxycholic acid on the synthesis of nitric oxide (NO), elevated production of which could be important in the pathogenesis of autoimmunity. Ursodeoxycholic acid (0.1-1000 microM) inhibited NO production by bacterial lipopolysaccharide-activated J774 macrophages in a concentration-dependent fashion, but the cytotoxicity was also evident at higher concentrations (250 and 1000 microM). Ursodeoxycholic acid did not have any effect on the activity of NO synthase that had already been induced. Treatment with lipopolysaccharide led to a significant expression of NO synthase mRNA that was significantly reduced by ursodeoxycholic acid. Findings indicated that ursodeoxycholic acid inhibited NO synthesis by inhibiting the induction of NO synthase, rather than its catalytic activity. Ursodeoxycholic acid therapy may exert a beneficial effect, in part, by attenuating the production of NO.

Animals↗

Expression of heat shock proteins HSP70 and HSP90 in endometrial carcinomas. Correlation with clinicopathology, sex steroid receptor status, and p53 protein expression.

BACKGROUND: It has been suggested that heat shock proteins HSP70 and HSP90 are involved in the functional modulation of sex steroid receptors and are expressed in normal endometrium. However, little is known about the expression of HSP70 and HSP90 in endometrial carcinomas. METHODS: The immunohistochemical reactivity of monoclonal antibodies against HSP70 and HSP90 was examined in 42 endometrial carcinomas, and the presence or absence of correlation with the clinicopathologic features, sex steroid receptor status, and p53 protein expression was analyzed. RESULTS: Expression of HSP70 was found in 52% of endometrial carcinomas and was correlated with nonendometrioid histology (P < 0.05), a poorly differentiated state (P < 0.01), p53 protein expression (P < 0.01), and absence of sex steroid receptors (P < 0.001) in the tumor. By contrast, strong expression of HSP90 was observed in 29% of endometrial carcinomas, and occurred more frequently in well-differentiated carcinomas that were positive for sex steroid receptors. CONCLUSIONS: Both HSP70 and HSP90 are significantly correlated with the histology and the sex steroid receptor status of endometrial carcinomas. Expression of HSP70 may be associated with a loss of sex steroid receptors in either nonendometrioid or poorly differentiated carcinoma of the endometrium, which frequently exhibits p53 protein expression. Conversely, strong expression of HSP90 may indicate high levels of sex steroid receptors in the tumor cells.

Adult↗

Malignant plexiform tumor of the uterus: an unusual variant of epithelioid leiomyosarcoma.

A 46-year-old woman with the complaint of hypermenorrhea underwent hysterectomy for a presumed uterine myoma. The solid tumor in the myometrium was gray in color, was 4 cm in diameter, and showed hemorrhage and necrosis. Histologically, the tumor consisted of round or polygonal cells arranged in cords and nests, and its histological features closely resembled those of plexiform tumor which has been reported as a benign, epithelioid smooth muscle tumor of the uterus. In the tumor in our patient, however, mild nuclear atypia and two to three mitoses/10 high-power fields were present. Two months after the hysterectomy, the patient was found to have metastatic foci in the lumbar vertebrae and iliac bone, which contained tumor cells with the same histological features. Accordingly, the present tumor might be interpreted as a malignant plexiform tumor of the uterus, an unusual variant of epithelioid leiomyosarcoma.

Biomarkers, Tumor↗

Effects of calcium in continuous cardioplegia on myocardial protection.

The effects of calcium (Ca) on a hyperkalemic cardioplegic solution for continuous cardioplegia were examined in an isolated perfused working rat heart model. The coronary arteries were perfused with a modified Krebs-Henseleit bicarbonate buffer (K-H) solution, containing various concentrations of Ca (0.1, 0.6, 1.2, and 2.5 mmol/l) and a high concentration of potassium (20 mmol/l), for 180 min, after which cardiac arrest was induced at 37 degrees C for 180 min. Cardiac function and creatine kinase (CK) were measured. In the control group, K-H solution was infused in place of the cardioplegic solution, and cardiac arrest was not induced. No significant differences were observed between the groups infused with the K-H solution containing Ca concentrations of 0.6, 1.2, and 2.5 mmol/l in the percent recovery of aortic flow (82.1 +/- 2.9%, 80.6 +/- 2.0%, and 71.5 +/- 3.7% (mean +/- SEM) respectively) or in the recovery of other indices of cardiac function, or in CK leakage. There were also no significant differences in the recovery of cardiac function and CK leakage between these groups and the control group. In the Ca 0.1 mmol/l group, however, the characteristic Ca paradox was observed. These findings suggest that if the Ca concentration in a cardioplegic solution is higher than 0.6 mmol/l during continuous cardioplegia, excellent cardioprotective effects will be achieved.

Animals↗

Parathyroid hormone induces a rapid increase in the number of active osteoclasts by releasing histamine from mast cells.

Intraperitoneal injection (i.p.) of parathyroid hormone (PTH, 50 micrograms/kg) into young rats (7-day postnatal) induced, within one hour, an increase in the number of osteoclasts which showed well-developed clear zone. Histological observations showed that degranulation of mast cells adjacent to bone surface occurred within 15 min after the injection of PTH. Injection of histamine into rats pretreated with cimetidine, an H2 antagonist of histamine, also induced an increase in the number of active osteoclasts within one hour after the injection of histamine. Furthermore, pretreatment of mice with an H1 antagonist, pyrilamine, completely inhibited the rapid increase in the number of active osteoclasts by PTH. These results suggest that PTH may stimulate osteoclasts to the active form by releasing histamine from mast cells and by stimulating H1 receptors for histamine.

Animals↗

Effects of daily injections of melatonin on locomotor activity rhythms in rats maintained under constant bright or dim light.

It has been demonstrated that daily melatonin injections entrain free-running locomotor activity rhythms in rats kept in constant darkness, and synchronize disrupted circadian patterns of wheel-running activity under constant light. Contrary to these previous observations, our result did not show that daily injections of melatonin synchronize disrupted locomotor activity in rats maintained under constant bright light. On the other hand, daily treatment with melatonin entrained the intact free-running rhythm in rats kept in constant dim light. This entrainment took place only when the time of injection corresponded to the activity onset time, and similar results were obtained in blinded rats. Pinealectomy had no influences on either the free-running rhythm or melatonin-induced entrainment. To examine whether a behavioral feedback mechanism is involved in melatonin-induced entrainment, rats were immobilized for 3 h after each daily melatonin injections. This did not interfere with melatonin-induced entrainment. These results suggest that the mechanism underlying melatonin-induced entrainment of activity rhythms may be different from those in photic and behavioral entrainment.

Animals↗

Effects of calcitonin and parathyroid hormone on the distribution of F-actin in the clear zone of osteoclasts in vivo.

To elucidate the relation between the distribution of F-actin bands in the clear zone and the bone-resorbing activity of osteoclasts in vivo, the endocranial surfaces of calvariae from 7-day-old Wistar rats were stained with F-actin-specific fluorescein isothiocyanate-labeled phalloidin (FITC-phalloidin) with and without the intraperitoneal injection of the calcium-regulating hormones, calcitonin (CT), and parathyroid hormone (PTH). Some specimens were double-stained with FITC-phalloidin and a monoclonal antibody, ED1, which stained monocytes and macrophages. In normal rats, almost 80% of the osteoclasts showed ring-shaped F-actin bands in the clear zone, and the remaining 20% showed arch- or line-shaped F-actin bands. From 15 min to 1 h after the injection of CT (salmon, 10 mg/kg), the number of osteoclasts with ring-shaped F-actin bands decreased significantly. At 1 h, few F-actin bands were detected in osteoclasts, which were still stained by ED1. However, these F-actin bands recovered to the normal level at 6 h. On the other hand, from 15 min to 6 h after the injection of PTH (bovine, 50 mg/kg), the number of osteoclasts with arch- or line-shaped F-actin bands decreased significantly. These results indicate that osteoclasts with arch- or line-shaped F-actin bands in the clear zone had lower bone-resorbing activity than those with ring-shaped F-actin bands, and that the formation of bands could be controlled by calcium-regulating hormones over the course of a few hours. Observation of the endocranial surfaces of calvariae might be useful for examining factors which affect the activities of osteoclasts in vivo.

Actins↗

Primary non-Hodgkin malignant lymphoma of the male breast.

A case of primary non-Hodgkin lymphoma of the male breast is reported. The patient was a 76-year-old Japanese with a history of bilateral gynecomastia. After the patient had received sex hormone treatment for the gynecomastia, rapid growth of a tumor in the right breast was noted, with regression of a contralateral breast lesion. Clinically, inflammatory breast cancer was suspected, and right mastectomy with ipsilateral axillary lymph node dissection was performed after intraarterial infusion chemotherapy using a cis-platinum derivative. The histology of the surgical specimen was non-Hodgkin malignant lymphoma of the diffuse large cell type, with focal tumor necrosis. Immunohistochemically, the tumor cells showed a B-cell nature. The patient is currently well without disease 39 months after surgery.

Aged↗

Clinicopathologic study of PRAD1/cyclin D1 overexpressing lymphoma with special reference to mantle cell lymphoma. A distinct molecular pathologic entity.

Mantle cell lymphomas (MCLs) are frequently associated with the overexpression of PRAD1/cyclin D1, activated by 11q13 translocation and its molecular counterpart BCL-1 gene rearrangement. We recently described the correlation of positive nuclear staining using monoclonal antibody against a PRAD1/cyclin D1 product with mRNA overexpression in MCLs. In the present study, we immunohistochemically investigated the PRAD1/cyclin D1 protein in a large series of 334 lymphoproliferative disorders, including 39 cases of MCLs on paraffin sections. Based on the cyclin D1 positivity, CD5 expression, and the morphologic features of the tumor tissue, four groups of MCL-related lesions were identified among the B-cell lymphomas examined: 36 cases with cyclin D1 overexpression, 35 (95%) of which exhibited CD5-positivity and MCL-morphology (Group 1); four cases of lymphomas with MCL morphology and CD5 expression but lacking cyclin D1 overexpression (Group II); four cases of lymphomas without cyclin D1 overexpression and surface CD5 but that fall within the morphologic boundaries of MCLs (Group III); and 11 cases of CD5-positive diffuse large cell lymphomas without cyclin D1 overexpression (Group IV). The Group I cases demonstrated quite homogeneous clinicopathologic features identical to those of MCLs. This group showed a poor prognosis (11% had 5-year survival), which is highly contrasted with that of Group II (100%). Although the four groups of MCL-related lesions sometimes overlapped in their histologic or phenotypic spectrums, each appeared to show distinct clinicopathologic and prognostic profiles. Our study provides a basis for further clarification of the nature of the neoplasms of Groups II, III, and IV. Moreover, this comprehensive study may indicate that the overexpression of PRAD1/cyclin D1 is biologically essential to defining MCLs.

Aged↗

Melatonin accelerates reentrainment of circadian locomotor activity rhythms to new light-dark cycles in the rat.

We examined whether continuous melatonin administration through subcutaneously implanted silastic tubing accelerates reentrainment of circadian rhythms of locomotor activity to shifted illumination cycles. We found that rats required less time to reentrain to an advanced or delayed phase shift of a light-dark cycle while carrying a silastic implant filled with melatonin than while carrying an empty implant. These results suggest that continuous administration of melatonin accelerates the reentrainment of the circadian locomotor activity rhythm to a new light-dark cycle.

Activity Cycles↗

[A report of surgical treatment for atherosclerotic aneurysm in the aortic arch associated with type III acute aortic dissection].

A 75-year-old man was admitted to our hospital because of severe chest pain. A chest CT scan demonstrated an atherosclerotic true aneurysm measuring 50 mm in diameter located just distal to the aortic arch as well as a DeBakey type III dissection. Although the patient received medical therapy, the size of the true aortic aneurysm increased to 71 mm and the false lumen of the descending aorta was also enlarged after three weeks. At 11 weeks after admission, the aortic arch and the proximal portion of the descending aorta were replaced with a 32 mm Hemashield graft using moderate hypothermic selective cerebral perfusion. The postoperative course was uneventful, and there were no neurological complications. Coexistence of atherosclerotic true aneurysm and acute aortic dissection appears to increase the risk of aortic rupture, early surgical treatment should be considered.

Acute Disease↗

[A case report of transaortic mitral valve replacement in Marfan's syndrome].

One-stage operation was successfully performed in 30-year-old male with annulo aortic ectasia and mitral valve regurgitation secondary to Marfan's syndrome. The replacement of the mitral valve was performed through aortic root. The transaortic mitral valve replacement employed here should prove useful for similar cases requiring reconstruction of aortic root and replacement of mitral valve simultaneously in Malfan's syndrome.

Adult↗

[A case report of surgical treatment for acute mitral insufficiency associated with acute gastric lesion].

A 76-year-old female was admitted to our hospital due to anterior chest pain and dyspnea. Mitral regurgitation due to prolapse of the posterior leaflet was detected by UCG. After admission, massive gastric hemorrhage was observed. Because hemostatic therapy using endoscopy was not effective, partial gastrectomy was performed. The origin of the hemorrhage, an acute gastric ulcer, was located on the side of the minor curvature of the corpus ventriculi. After gastrectomy, the patient underwent medical treatment using an IABP, but the left heart failure was not reduced, and the pulmonary edema worsened. At 18 hours after gastrectomy, MVR was performed. The cause of regurgitation is torn chordae of the posterior leaflet. The postoperative course was good, and the patient is doing well in NYHA class 1. This case is the first report of acute mitral insufficiency associated with acute gastric lesion in Japan.

Acute Disease↗

[A case report of Stanford type A acute thrombosed aortic dissection complicating cardiac tamponade].

An 85-year-old man was admitted with shock due to cardiac tamponade. Plain computed tomography showed a dilated ascending aorta but did not clearly show an aortic dissection. We performed an emergency operation with median sternotomy without the benefit of findings from enhanced computed tomography and aortography. Soon after the bloody pericardial effusion was decompressed during the operation, bleeding from the ascending aorta occurred. An intimal tear was found in the distal ascending aorta, and the pseudolumen was filled with fresh thrombus. The ascending aorta was replaced. The patient had an uneventful postoperative recovery and was discharged 1 month after the operation. We conclude that patients with Stanford type A acute thrombosed aortic dissection complicating cardiac tamponade should undergo early graft replacement.

Acute Disease↗

[Injury to ascending aorta by cross-clamp--histologic evaluation].

To evaluate the injury to ascending aorta by cross-clamp, the trauma to the vessel wall was examined microscopically and the occlusive intensity of the vascular clamp was measured. Six patients were underwent total replacement of the ascending aorta and the aortic arch for aortic dissection. The ascending aorta and the aortic arch were resected during operation, the clamped regions of the ascending aorta were cut into the four pieces (the distal site, two part of the medial site, the proximal site applied by the vascular clamp) after operation. The four pieces of the ascending aorta were examined microscopically. The occlusive intensity of the vascular clamp were measured at the distal site, the medial site, and the proximal site by the load-measuring scale. The trauma to the vessel wall were classified to three degrees (grade 1 to grade 3). Grade 1 showed the minimal changes--narrowing of interstices between collagen fibers and muscle fibers in the media. Grade 2 showed the moderate changes--decrease of collagen fibers, atrophy and disruption of smooth muscle and elastic fiber in the media. Grade 3 showed the severe changes--disruption of the intima and defluvium of endothelial cells. The occlusive intensity of the vascular clamp were 1.0 kg at the distal site, 1.9 kg at the medial site and 3.6 kg at the proximal site, respectively. In the microscopic examinations, grade 1 changes were most frequent at the distal site, grade 1 and grade 2 changes were observed equally at the medial site, grade 3 change was observed only at the proximal site. The degree of the trauma to the vessel wall becomes severer in proportion to increase of the occlusive intensity of the vascular clamp.

Adult↗