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Biomedical subjects

M Kusano

Publications and source records attributed to M Kusano.

At least 37 records · Page 2Linked to original sources

Acceleration of thrombomodulin gene transcription by retinoic acid: retinoic acid receptors and Sp1 regulate the promoter activity through interactions with two different sequences in the 5'-flanking region of human gene.

The interactions between retinoic acid- (RA)-dependent transcriptional regulatory sequences of the 5'-untranslated region of the thrombomodulin gene and nuclear RA-responsive proteins were studied using human pancreas BxPC-3 cells. Deletion mutants of pTM-CAT plasmid revealed the presence of distal and proximal RA-responsive regions containing direct repeat with 4 spaces (DR4) and three of four Sp1 sites, respectively. Cotransfection of a pTM-CAT plasmid with expression plasmids of RA receptors (RARalpha, RARbeta, and RARgamma) augmented the promoter activity under the condition of lower retinoid X receptor-alpha (RXRalpha) expression, whereas the activity was greatly diminished when RXRalpha was highly expressed. An electrophoretic mobility shift assay with cDNA containing the DR4 indicated that heterodimers of RAR and RXRalpha interacted with the DR4 site, although the interaction gradually disappeared with the increase in the ratio of RXRalpha/RAR. On the other hand, Sp1 protein interacted especially with the tandem Sp1 site corresponding to the first and second Sp1 sequences of the four Sp1 sites in the proximal RA-responsive region. The binding of Sp1 to Sp1 sites was independent of RAR-RXR heterodimer but increased with the increase in Sp1 concentration in the presence of unknown factor(s) of reticulocyte lysate. Upon treatment of the cells with RA, time-dependent increases in the ratio of RARbeta to RXRalpha and the phosphorylated form of Sp1 were observed. We concluded that two genomic DNA regions, the DR4 site (-1531 to -1516) and the first and second Sp1-binding sites (-145 to -121), were involved in the RA-dependent augmentation of thrombomodulin gene expression through increased interactions of the two regions with heterodimer of RAR-RXRalpha and nuclear Sp1, respectively.

Binding Sites↗

Significance of involvement by squamous cell carcinoma of the ducts of esophageal submucosal glands. Analysis of 201 surgically resected superficial squamous cell carcinomas.

BACKGROUND: Ductal involvement (DI) is often observed in superficial squamous cell carcinoma of the esophagus (SSCCE), defined as carcinoma with invasion limited to the submucosa. The purpose of this study was to clarify the clinicopathologic significance of DI in SSCCE. METHODS: Two hundred one surgically resected lesions from 140 patients with SSCCE were examined histopathologically. Clinicopathologic factors, such as macroscopic type, tumor location, maximum tumor size, depth of invasion, lymphatic and blood vessel permeation, lymph node metastasis, and prognosis, were examined to investigate the association between these factors and the presence of DI. RESULTS: Of the 201 SSCCE lesions, 43 (21.3%) had 152 DIs (1-32 DIs per lesion). The DI always remained in situ, and there were no tumors showing submucosal invasion through the DI. As for the relation between clinicopathologic factors and the presence of DI, multivariate analysis showed only maximum tumor size to correlate with the presence of DI (P < 0.0001). There were no significant differences between DI negative and DI positive lesions in tumor location, macroscopic type, lymphatic and blood vessel permeation, lymph node metastasis, or prognosis. In 83 mucosal carcinomas, including in situ carcinomas or carcinomas that invaded no deeper than the lamina muscularis mucosa, no lymph node metastasis was found, and the 5-year survival rate was 100% (unaffected by the presence of DI). Among these 83 lesions, DI was found in 11 (13.8%), of which 6 (7.2%) had DI extending to the submucosal layer. CONCLUSIONS: These results indicate that DI as a pathway of tumor spread to the deeper layer is of little significance in squamous cell carcinoma of the esophagus, and that mucosal carcinomas with DI that extends to the submucosa should not be classified as submucosal carcinoma.

Adult↗

Attenuated cardiovascular adjustment to sustained static exercise after carbohydrate loading.

We examined whether a higher plasma lactic acid (LA) concentration resulting from carbohydrate (CHO)-loading affects the cardiovascular responses to exercise through a greater activation of LA-induced metaboreflex. Before and after CHO-loading, LA concentration, mean arterial blood pressure (MAP), heart rate (HR), cardiac output (CO), rating perceived exertion (RPE), and integrated electromyogram (iEMG) of the vastus lateralis were studied during a sustained static knee extension of single legs in 16 volunteers. The CHO-loading comprised an exhaustive bout of one-legged cycling (73+/-3% of maximal oxygen uptake for 130-160 min) and consuming a low-CHO diet for 2-3 days and a high-CHO diet for the next 3 days. In the leg that performed the exercise (the experimental leg), the LA concentration after CHO-loading was significantly increased, but the magnitude of MAP, HR, and CO responses during static exercise was significantly decreased in parallel with a significant reduction of RPE and iEMG. In the control leg, there were no changes in the variables before and after CHO-loading. These results suggest that the increased LA concentration resulting from CHO-loading did not affect the cardiovascular adjustment to the sustained exercise. Other mechanisms related to the reduction of RPE and iEMG seem to be responsible for the attenuated cardiovascular responses observed in the experimental leg after CHO-loading.

Adult↗

Histopathologic findings predicting lymph node metastasis and prognosis of patients with superficial esophageal carcinoma: analysis of 240 surgically resected tumors.

BACKGROUND: If it were possible to elucidate the histopathologic findings predicting lymph node metastasis and prognosis in superficial squamous cell carcinoma of the esophagus (SSCCE), they could be used as markers to identify patients who do not require additional surgical resection after endoscopic mucosal resection (EMR). METHODS: Two hundred forty surgically resected SSCCEs were examined histopathologically. Histopathologic factors including vertical tumor invasion depth in the submucosal layer (VTIDsm), degree of nuclear atypia (low, one point; high, two points), growth pattern (expansive, one point; infiltrative, two points), and histologic grade (calculated by adding the latter two scores to obtain Grade 1, two points; Grade 2, three points; and Grade 3, four points) were evaluated to investigate the associations among these factors, lymph node metastasis, and prognosis. RESULTS: No lymph node metastasis was found in 54 patients with carcinoma limited to the lamina propria. Their 5-year survival rate was 100%. Multivariate analysis of 186 carcinomas invading beyond the lamina propria showed that lymphatic permeation correlated with lymph node metastasis (P<0.0001) and the presence of lymph node metastasis and a high histologic grade were independent factors indicating a poor prognosis (P = 0.0061 and 0.023, respectively). In 53 patients whose tumors had invaded the lamina muscularis or slightly invaded the submucosa (VTIDsm <500 microm), no lymph node metastasis was found in the lymphatic permeation negative and blood vessel permeation negative patients with VTIDsm values <200 microm and histologic Grades 1 or 2. CONCLUSIONS: Lymphatic permeation is a good predictor of lymph node metastasis in patients with SSCCE. Lymph node metastasis and the histologic grade are independent prognostic factors. Vessel permeation, VTIDsm, and histologic grade were found to be important factors for identifying patients who did not require additional surgical treatment after EMR.

Biomarkers, Tumor↗

Iodine absorption after intraoperative bowel irrigation with povidone-iodine.

PURPOSE: Povidone-iodine is a commonly used intrarectal tumoricidal agent in patients undergoing colorectal surgery. The aim of this study was to assess systemic absorption of total iodine and its effect on thyroid function after intrarectal application. METHODS: Twenty patients with carcinoma of the rectum received intraoperative irrigation with either povidone-iodine (Group A; n = 10) or physiologic saline (Group B; n = 10). Ten patients with carcinoma of the sigmoid colon (group C) were treated the same as Group A. Electrolyte, total iodine, triiodothyronine, thyroxine, and thyroid-stimulating hormone values were measured in serum preoperatively and before intraoperative irrigation and immediately, ten minutes, 1 hour, 6 hours, 24 hours, and two weeks after irrigation. RESULTS: No significant changes occurred in serum electrolytes. A significant uptake of the total iodine was demonstrated in each group. Total iodine levels examined immediately, ten minutes, and one hour after irrigation in Group C were significantly higher than those examined in Group B. Maximum values were obtained one hour after irrigation in Groups A and B and six hours after irrigation in Group C. No significant changes occurred in triiodothyronine, thyroxine, and thyroid-stimulating hormone levels among the three groups. The decrease in triiodothyronine levels after surgery was demonstrated in each group. We noted a decrease after surgery in thyroxine levels for Groups A and B and in thyroid-stimulating hormone levels for Group B. Those hormones were not affected by the administration of povidone-iodine. CONCLUSION: High serum levels of iodine did not cause organ toxicity, suggesting that a single use of intraoperative bowel irrigation with povidone-iodine may be performed with practically negligible risk.

Adult↗

Pancreatic involvement by non-Hodgkin's lymphoma.

A case of pancreatic involvement by non-Hodgkin's lymphoma is presented. The patient, a 63-year-old man had a large tumor in the head of the pancreas, without obstructive jaundice. Invasion of the tumor into the duodenum and transverse colon induced progressive anemia and ileus. Therefore, pancreatoduodenectomy and right hemicolectomy were performed, although a definitive preoperative diagnosis was not obtained. This tumor was identified, by histopathology and immunohistochemistry, as diffuse mixed type lymphoma with a B-cell phenotype. Postoperatively, the patient had severe congestive heart failure, and he died without receiving chemotherapy. It is important to establish a definitive diagnosis for this disease, to remove the tumor, and to treat the patient with appropriate chemotherapy.

Fatal Outcome↗

Measurement and evaluation of gastric emptying using radiopaque barium markers.

To simplify assessment of gastric emptying, we have developed a radiopaque barium marker method. The subjects were 11 healthy volunteers, 30 patients with progressive systemic sclerosis, 16 patients with dysmotility-like dyspepsia, 7 patients with irritable bowel syndrome, and 6 patients with diabetes mellitus. We tested three types of radiopaque markers with manometry by a three-channel strain gauge transducer. The 4.5-mm ring-shaped markers with a specific gravity of 1.2 were emptied from the stomach in correlation with the number of high-amplitude (>50 mm Hg) antral contractions. The percentage of residual markers at 2 hr was significantly (P < 0.05) lower in patients with irritable bowed syndrome than in normal controls, and at 5 hr it was significantly (P < 0.05) higher in patients with systemic sclerosis with esophageal dysmotility, dysmotility-like dyspepsia, or diabetes than in normal controls. This radiopaque barium marker method may be useful as a screening test for determining whether gastric emptying is rapid or delayed.

Adult↗

Nematicidal alkaloids and related compounds produced by the fungus Penicillium cf. simplicissimum.

A new nematicidal alkaloid, peniprequinolone (1), together with the known alkaloids penigequinolones A and B (2a, 2b), 3-methoxy-4-hydroxy-4-(4'-methoxyphenyl)quinolinone (3), and 3-methoxy-4,6-dihydroxy-4-(4'-methoxyphenyl)quinolinone (4), were isolated from Penicillium cf. simplicissimum (Oudemans) Thom. Cyclopenin (5) and a compound (6a/6b) structurally related to cyclopenin also were isolated from the fungus, and their structures were established by spectroscopic analysis. The biological activities of 1, 2, 3, 4, and 5 were examined by a bioassay with root-lesion nematodes.

Alkaloids↗

Immunohistochemistry for parathyroid hormone-related protein (PTHrP) in benign and malignant mammary mixed tumors of dogs with and without hypercalcemia.

We evaluated the expression of parathyroid hormone-related protein (PTHrP) by immunohistochemistry in eight benign and malignant mammary mixed tumors of dogs with (n = 4) and without (n = 4) hypercalcemia. Positive immunoreactive staining for PTHrP was observed in all four tumors from hypercalcemic dogs. The mammary tumors from 2 of the 4 normocalcemic dogs stained positively for PTHrP, but the numbers of immunoreactive cells and intensity of the immunoreaction were less than in the hypercalcemic dogs. In the other 2 tumors without hypercalcemia, the tissue samples were negative for PTHrP.

Animals↗

[Motility disorders of the esophagus, excluding achalasia].

Esophageal motor disorders can be primarily focused in the esophagus or secondarily related to a systemic disease. Based on the manometric findings, primary esophageal motor disorders can also be classified into achalasia and spastic disorders, such as diffuse esophageal spasm, nutcracker esophagus, hypertensive lower esophageal sphincter, and nonspecific esophageal motility disorders.

Adult↗

[Esophageal peristalsis, lower esophageal function, and the methods of their evaluation].

Esophageal peristalsis and lower esophageal sphincter(LES) function have an influence on gastroesophageal reflux disease(GERD). Incomplete contraction during primary and secondary peristalsis leads to poor clearance of refluxed gastric acid. Failure of LES function can result in a low basal LES pressure, absent or incomplete LES relaxation after swallowing, or an inadequate increase of LES pressure accompanying gastric activity. In addition, transient LES relaxation(TLESR) has been suggested as an important factor in GERD. Recent studies have indicated that TLESR has a relationship to nitric oxide(NO) and cholecystokinin(CCK).

Esophagogastric Junction↗

Association of matrilysin expression with recurrence and poor prognosis in human esophageal squamous cell carcinoma.

Matrix metalloproteinase-7 (matrilysin) has been implicated in tumor invasion and metastasis as well as tumor initiation and growth. In this study, we analyzed an association between immunohistochemically detected matrilysin expression at the invasive front in esophageal squamous cell carcinomas and clinicopathological characteristics and determined whether matrilysin predicts recurrence and/or survival Matrilysin expression at the invasive front was detected in 49% of 100 carcinoma tissues and was associated with the depth of invasion (P < 0.0001), advanced tumor stage (P = 0.0159), recurrences (P = 0.0002), and recurrences within the first postoperative year (P = 0.002). Patients with matrilysin-positive carcinoma had a significantly shorter disease-free and overall survival time than did those with a matrilysin-negative one (P < 0.0001). Matrilysin remained a significant predictive value for disease-free and overall survival in multivariate analysis, including conventional clinicopathological factors (P = 0.0007 and 0.0004, respectively). Our results suggest that matrilysin may play a key role in the progression of esophageal carcinoma and that its detection may be useful for the prediction of recurrence and poor prognosis and, possibly, for selecting patients for anti-matrix metalloproteinase therapy.

Carcinoma, Squamous Cell↗

Anorectal function after anterior resection with side-to-side anastomosis for carcinoma of the rectum.

PURPOSE: The aim of this study is to demonstrate whether anorectal function after anterior resection with side-to-side anastomosis results in better clinical outcomes than end-to-end anastomosis in patients with carcinoma of the upper half of the rectum. METHODS: Anorectal function was studied in two groups of patients who had anterior resection, those with end-to-end anastomosis (Group E; n = 11) and those with side-to-side anastomosis (Group S; n = 11). Eight control subjects who had sigmoid colectomy for carcinoma were also studied. Each patient underwent manometric study and was questioned about clinical bowel symptoms before the operation and 3, 6, and 12 months postoperatively. RESULTS: The median length of residual rectum in both Group S and Group E was 7 cm. No significant difference was observed in maximum anal resting pressure and maximum squeeze pressure between the groups before and after operation. Maximum tolerable volume in Group S was significantly higher than that in Group E and was close to that in the control group at each postoperative interval. Median volumes in Group S were 200 ml (3 months), 220 ml (6 months), and 220 ml (12 months). Median volumes in Group E were 140 ml (3 months), 150 ml (6 months), and 175 ml (12 months). Bowel frequency per 24 hours at three and six months postoperatively was significantly greater in Group E than in Group S or the control group. Median frequency in Group E was four times (3 months) and three times (6 months) per 24 hours. Median frequency in both Group S and the control group was two times (3 months) and two times (6 months) per 24 hours. Postoperative urgency of defecation was not found in Group S, significantly less frequent than in Group E at three months. CONCLUSION: Side-to-side anastomosis may lead to a better clinical outcome than end-to-end anastomosis for carcinoma of the upper half of the rectum in the adaptation phase.

Aged↗

The effect of vaginal delivery on the pelvic floor.

This study was undertaken to determine the effects of vaginal deliveries on anorectal function, and to analyze the possible clinical, physiological, and radiological risk factors predisposing to damage of the pelvic floor musculature. We studied 25 consecutive women with a mean age of 32 years old, 3 months after vaginal delivery, 17 of whom were primiparae and 8, multiparae. The symptoms of anal incontinence were assessed, and anorectal manometry, rectal sensation, and radiological measurements of the anorectal angle and pelvic floor position at rest, on squeezing, and on straining were performed. As a control, six nulliparous women underwent the same examinations. Pelvic floor descent in both the primiparae and multiparae was significantly greater at rest and on squeezing than that in the nulliparous women. Furthermore, pelvic floor descent on straining was greater in the multiparae than in the nulliparous women (P = 0.028). An analysis of the 17 primiparae showed that prolonged duration of the second stage of labor and third-degree perineal tears were important factors predisposing to pelvic floor descent. In fact, 3 of the 17 primiparae (17%) had anal incontinence. These findings indicate that vaginal delivery may cause pelvic floor descent, an obtuse anorectal angle, and bowel symptoms.

Adult↗

Metastatic seeding of bile duct carcinoma in the transhepatic catheter tract: report of a case.

We describe herein the case of a 51-year-old woman in whom metastatic tumor seeding of the percutanenous transhepatic biliary drainage tract occurred following a pancreatoduodenectomy for carcinoma of the distal common bile duct. An abdominal computed tomography scan done 6 months after the initial operation detected a hepatic lesion located at the site of the previous percutaneous transhepatic biliary drainage tract. Implantation of bile duct carcinoma in the drainage tract was diagnosed, and the recurrent tumor was successfully resected by performing a subsegmentectomy of segment 3 and removal of the adjacent abdominal wall. At present, 5 years and 4 months after the second resection, the patient is in good health without any signs of recurrence. This case report demonstrates that an aggressive surgical approach should be performed for tumor seeding of a transhepatic biliary catheter tract.

Carcinoma, Squamous Cell↗

Immediate increase of portal pressure, reflecting sinusoidal shear stress, induced liver regeneration after partial hepatectomy.

The mechanisms whereby hepatocytes in the normal liver can be primed for replication following partial hepatectomy (PHx) are poorly understood. To determine whether "shear stress," which is induced by acute portal hypertension after PHx, is involved in liver regeneration, we studied liver regeneration in rats with splenic transposition (SPT) in which we can minimize the postoperative elevation of portal pressure. Rats underwent 70% PHx following splenic transposition or sham surgery and were killed at various time points to measure portal pressure and other factors. In the control groups, the portal pressure was significantly increased immediately after surgery, peaking at 48 h, and returning to near the preoperative levels by 168 h after PHx. In the SPT group, although portal pressure increased immediately, it decreased to the control levels 6 h after PHx and thereafter repeatedly increased. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) levels peaked at 24 and 6 h after PHx, respectively. Proliferative cell analysis was done using MIB-5 antibody, and there were no significant differences between the two groups. Furthermore, liver weight was restored in the same way in both groups. Taken together, the results suggest that an immediate increase in portal pressure is necessary for the initiation of liver regeneration.

Animals↗