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Biomedical subjects

S Wada

Publications and source records attributed to S Wada.

At least 73 records · Page 4Linked to original sources

A germline mutation, 1001delC, of the multiple endocrine neoplasia type 1 (MEN 1) gene in a Japanese family.

Multiple endocrine neoplasia type 1 (MEN 1) is an autosomal dominant inherited disorder characterized by tumors of the enteropancreas, parathyroid and anterior pituitary. The MEN 1 gene was recently cloned, and germline mutations of the gene have been demonstrated in cases of MEN 1. Here, we report a Japanese family with a germline mutation of the MEN 1 gene. The proband (44 y.o., male) had primary hyperparathyroidism (PHP) and pancreatic carcinoid, and his older sister (50 y.o.) had a history of parathyroidectomy for primary hyperparathyroidism at the age of 40. Clinical examination revealed no evidence of PHP or other MEN 1-related tumors in his son. Direct sequencing analysis revealed a heterozygous germline mutation (1001delC) at codon 297 in exon 6 of the MEN 1 gene in the proband and his son. Loss of heterozygosity (LOH) was also found in the resected parathyroid tissue of the proband. The deletion of cytosine 1001 observed in this case induces a frame shift, which causes the appearance of a stop codon (TAG) at codon 367. This mutation appears to be associated with tumors of the endocrine tissues in the cases studied.

Adult↗

Acute respiratory failure caused by vinorelbine tartrate in a patient with non-small cell lung cancer.

We describe a case of vinorelbine tartrate (VNR) associated acute respiratory failure. A 65-year-old man with non-small cell lung cancer developed acute respiratory failure 50 minutes after his first infusion with VNR in combination with mitomycin-C. The patient was treated with furosemide, dopamine and high-dose methylprednisolone, and recovered with no discernible sequelae. Although clinical trials have shown that respiratory symptoms associated with VNR treatment have only rarely been observed and the putative mechanism remains to be elucidated, patients receiving VNR should be monitored carefully, particularly in the first few hours after intravenous administration.

Acute Disease↗

Multiple bile duct biopsies using a sheath with a side port: usefulness of intraductal sonography.

OBJECTIVE: We clarified the number of biopsies required to determine malignancy of the biliary tract on the basis of the type of bile duct tumor. SUBJECTS AND METHODS: Patients with a biliary tract malignancy (n = 33) and a benign biliary stenosis (n = 3) underwent biopsy via the percutaneous transhepatic route. We performed intraductal sonography using a 20-MHz probe with a 2.0-mm diameter. The sonographic findings were prospectively classified as polypoid, circular, or semicircular. The tip of a long 9-French sheath with a side port was wedged into the stenosis, and six specimens were obtained with a 1.8-mm-diameter forceps with serrated cups. RESULTS: When cholangiography or intraductal sonography showed a polypoid lesion, the sensitivity of two biopsies was 100% (6/6). When cholangiography showed a stenotic lesion, the sensitivity of nine biopsies (96%, 26/27) was superior to that of two biopsies (74%, 20/27; p < 0.05). When intraductal sonography showed a circular lesion, the sensitivity of three biopsies (100%, 14/14) was superior to that of a single biopsy (64%, 9/14; p < 0.05). When it showed a semicircular lesion, the sensitivity of nine biopsies (92%, 12/13) was superior to that of two biopsies (54%, 7/13; p < 0.05). CONCLUSION: Bile duct biopsy using a sheath with a side port has a high sensitivity. However, the number of biopsies required depends on the cholangioscopic and intraductal sonographic appearance of the tumor.

Aged↗

Characteristic magnetic resonance imaging for neurological assessment in HELLP syndrome with eclampsia: a case report.

HELLP syndrome is a complication of pregnancy characterized by hemolytic anemia, elevated liver enzymes, and low platelets. We describe a patient who suffered a generalized tonic seizure as a clinical onset. Magnetic resonance imaging (MRI) of the brain showed high intensity lesions on T2-weighted images and low- and iso- intensity on T1-weighed images. The patient fully recovered and on follow-up MRI the abnormal lesions were almost totally resolved. The sensitivity and specificity of MRI is useful in distinguishing this complication of pregnancy from cerebral apoplexy, brain tumor, epilepsy and other causes.

Adult↗

Expression of cyclooxygenase-2 in patients with bladder carcinoma.

PURPOSE: Cyclooxygenase-2 is considered to have an important role in the development of metastasis in cancer due to angiogenesis function. The expression of cyclooxygenase-2 was found to be up-regulated in colorectal carcinoma and other cancers. We investigated cyclooxygenase-1 and 2 expressions in patients with bladder cancer, chronic cystitis and normal bladder. MATERIALS AND METHODS: A total of 118 specimens were obtained from patients treated at Osaka City University Hospital for bladder cancer, including 10 with chronic cystitis and 8 with normal bladder tissue. Immunohistochemistry, with affinity purified antibodies against human cyclooxygenase-1 and 2 that did not have cross-reactivity with each other, and reverse transcriptase polymerase chain reaction to study the messenger RNA expression were performed. RESULTS: Although no marked expression of cyclooxygenase-2 was observed in the normal bladder, it was slightly seen in infiltrative inflammatory cells of chronic cystitis, and a higher expression was found in cancer cells. The extent and intensity of immunoreactive cyclooxygenase-2 polypeptides in cancer cells was statistically much greater than those in cells from normal bladder tissue. Moreover, correlation between cyclooxygenase-2 expression and tissue type or progression of bladder cancer was observed. Cyclooxygenase-2 expression was higher in grade 3 bladder cancer than in grade 1, and was higher in advanced than in early stage cancer. CONCLUSIONS: These results demonstrate that generated cyclooxygenase-2 in the cells of patients with bladder cancer might be significant in the proliferation of bladder malignant cells and development of invasions.

Adult↗

The volume limit in fluid resuscitation to prevent respiratory failure in massively burned children without inhalation injury.

We evaluated the accurate fluid requirement to prevent respiratory failure during the postresuscitation period in the resuscitation of massively burned children without inhalation injury. Forty-nine children were treated by similar fluid resuscitation and physiologic support protocols. Using a retrospective chart review, the children were divided into three groups as follows: Group N (no lung injury, n = 33, 41.4+/-18.7%TBSA burned), Group M (mild-to-moderate lung injury, n = 11, 73.7+/-17.1%TBSA burned) and Group S (severe lung injury, n = 5, 67.2+/-16.6%TBSA burned). Information about fluid resuscitation during the first 24 hr post-injury was collected and compared among the three groups. There was no significant difference in the hourly urine output and the resuscitation volume estimated by body weight and burn size among the groups. The volumes estimated by ml/kg/%TBSA burned were 7.0 ml/kg/%TBSA burned, 8.0 ml/kg/%TBSA burned, and 9.4 ml/kg/%TBSA burned in Groups N, M, and S, respectively. According to the fluid volume estimated by the burn index (BI; 1/2 of % second-degree burns plus % third-degree burns), the volumes were 13.8+/-4.0 ml/kg/BI, 14.4+/-4.4 ml/kg/BI, 18.8+/-3.7ml/kg/BI in Groups N, M, and S, respectively (Group N < Group S, p < 0.05). There was a significant positive correlation between the maximum respiratory index (AaDO2/PaO2) during the first week and the initial total volume administered (ml/kg/BI). These findings indicated that the fluid requirements to prevent postresuscitation respiratory failure in massively burned children might be estimated according to the depth of burned area in addition to body weight and burn size.

Blood Proteins↗

New local hyperthermia using dextran magnetite complex (DM) for oral cavity: experimental study in normal hamster tongue.

The possibility of dextran magnetite complex (DM) as a new hyperthermic material was examined in this study. DM suspension of 56 mg ml(-1) iron concentration was locally injected into the normal tongue of golden hamster. DM injected tongues were heated by 500 kHz alternating current (AC) magnetic field and its serial changes in temperature were recorded at 30-s intervals. The temperature of DM injected tongue was maintained at about 43.0-45.0 degrees C for 30 min by changing the AC magnetic field intensity. While temperature elevations of the contralateral tongue and the rectum were only of minor degree. In experiment on the extent of heating area, there was correlation between volume of black stain area and amount of the injected DM suspension (Y = - 18.1 + 1.94X, r = 0.931, P < 0.0001, n = 9 ). Histological examination after heating revealed brown uniform DM accumulation in the connective tissue between fibers of the tongue muscle. Except for vascular dilatations, no tissue damage was seen in the heated tongue. Thus, DM which has the possibility of selective and uniform heating in local hyperthermia might be useful for oral cancer therapy.

Animals↗

[Reconstruction of the cervical esophagus by interposition of the transverse colon].

Currently, the first choice viscus for reconstruction after total pharyngolaryngoesophagectomy is a jejunal interposition. This requires at least one end-to-side anastomosis in the pharyngo-jejunal anastomosis, esophago-jejunal anastomosis, or both due to the small diameter of the jejunum and round shape of the mesenterium. Furthermore, the jejunal graft experiences a spasm when the patient swallows. For such reasons the jejunal free graft is not suitable for swallowing. On the other hand, the transverse colon graft is more appropriate for reconstruction for the following reasons: it has a straight shape; end-to-end anastomosis is possible to both the pharynx and esophagus; and there are postoperative complications due to simple anastomosis of the remaining colon after graft removal. Blood vessel anastomoses, performed using microsurgery techniques, are followed by esophageal reconstructive anastomoses. Fifteen patients successfully underwent this type of reconstruction in our institution.

Aged↗

[Intraperitoneal cisplatin chemotherapy for ovarian cancer].

It is well known that the 5-year survival rate of advanced ovarian cancer patients greatly improved after the appearance of cisplatin. Recently, paclitaxel has been reported to be effective in the treatment of cisplatin-resistant ovarian cancer. However, control of intraperitoneal lesions is still the biggest problem in this treatment, and attention is focused on the development of effective approaches. Intraperitoneal chemotherapy is considered to be a mode of administration expected to have a direct effect on ovarian cancer by penetrating the tumor and an indirect effect via blood vessels. We examined the outcome and adverse drug reactions in 102 ovarian cancer patients who underwent repeated intraperitoneal administration of cisplatin in our hospital between April 1987 and April 1999. We confirmed that this method may greatly improve the five-year survival rate compared to intravenous administration.

Adenocarcinoma↗

[Bone metabolic markers and osteoporosis associated with diabetes mellitus].

Diabetes mellitus has been documented to affect bone and calcium metabolism. However, there is conflicting data on the frequency of fractures, changes of bone mineral density and the levels of bone metabolic markers in diabetes. These results may be related to heterogeneity of the patients in the studies, i.e., the presence or absence of insulin injection, body mass index, the amounts of intrinsic insulin secretion and/or insulin resistance. The combination of poor bone quality and frequent injurious falls would be expected to increase fracture incidence and a recent report revealed that older women with diabetes had a particularly increased risk of fractures. The metabolic effects of poor glycemic control lead to increased bone resorption without sufficient bone formation. With respect to bone metabolic markers, decreased levels of osteocalcin (OC) have been commonly reported. It is not known whether decreased OC is a predictive factor for fractures in diabetes, but the osteocalcin levels have been found to return toward the normal range after glycemic control. Since OC is known to be glycosylated, it is also possible that the measurement would be affected by high glucose conditions. The exact value of bone metabolic markers in diabetes has not been established, but measurement of osteocalcin may be a useful tool for evaluation of risk of fractures in diabetic patients.

English Abstract↗

[Appropriate clinical usage of calcitonin escape phenomenon and intermittent v.s. daily administration of calcitonin].

Since Calcitonin (CT) inhibits osteoclastic bone resorption, it has been widely used to treat metabolic bone disorders, such as Paget's disease of bone, malignancy-associated hypercalcemia, and osteoporosis. It is recognized, however, that continuous treatment with CT causes a loss of its inhibitory effects on bone resorption. We and other investigators have studied the mechanism and the results indicated that desensitization to CT was closely associated with the down regulation of the CT receptor (CTR). This down regulation was due not only to internalization of the receptor but also to reduced cell surface receptor concentration through inhibition of de novo CTR synthesis. An essential signal for osteoclast differentiation from its precursor cells, which was termed as ODF, was also found identical to tumor necrosis factor (TNF) related activation induced cytokine (TRANCE) and receptor activator of nuclear factor-kappa B ligand (RANKL). Using soluble RANKL and macrophage colony stimulating factor, we recently studied the mechanisms of the biological responses to CT in cells of human osteoclast lineage. The signaling pathway responsible for CTR down regulation in human osteoclasts is different from that observed in mouse osteoclasts: the activation of protein kinase A pathway is primarily responsible for CTR regulation in mouse osteoclasts, while the activation of protein kinase C was predominant in humans. Treatment with CT reduced concentration of cellular surface CTR and CTR mRNA expression also in human osteoclasts. The reduced specific binding, CTR mRNA levels and CT-sensitive adenylate cyclase responsiveness returned to the control levels by 96h after removal of CT. These results may suggest that intermittent administration of CT would be effective for the treatment of osteoporosis, resulting in reduced desensitization in CT target cells.

English Abstract↗

Expression of cyclooxygenase-2 in prostate carcinoma.

BACKGROUND: Nonsteroidal antiinflammatory drugs inhibiting cyclooxygenase (COX) enzyme activity in both its constitutive (COX-1) and inducible (COX-2) isoforms were shown also to inhibit the development of colon carcinoma in animal models. COX-2 is an inducer of angiogenesis of new blood vessels. The expression of COX-1 and COX-2 in prostate tissues from patients with prostate carcinoma was investigated using reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry. METHODS: Tumor specimens were obtained from 28 prostate carcinoma (PC) patients, 8 benign prostatic hyperplasia (BPH) patients, 1 prostatic intraepithelial neoplasia (PIN) patient, and 8 specimens of normal prostate tissue (NP). Affinity-purified COX-1 and COX-2 antibodies were used in immunochemistry. RESULTS: Very weak expression of COX-1 and marked expression of immunoreactive COX-2 in tumor cells was obtained. In contrast, expression of both isoforms was very weak in all cases of BPH and in the NP tissues. Immunoreactive COX-1 also was very weak in all cases of benign tissues. The extent and intensity of immunoreactive COX-2 polypeptides in tumor cells was statistically much greater than those of cells from BPH. Immunostaining with normal rabbit immunoglobulin G was completely negative. By RT-PCR analysis, enhanced expression of COX-2, but not COX-1, was observed in PC tissue. BPH displayed faint expression of COX-2. CONCLUSIONS: The results of the current study demonstrated that human prostate carcinoma cells generated COX-2, and that COX-2 might play an important role in the proliferation of prostate carcinoma cells. These findings suggest that inhibition of COX-2 development may lead not only to inhibition of the proliferation and metastasis of prostate carcinoma but also to the inhibition of prostate carcinogenesis.

Aged↗

Intraductal ultrasonographic assessment of coagulation depth during endoscopic microwave coagulation therapy in a canine model.

In order to examine the feasibility of endoscopic microwave coagulation therapy (MCT) for the treatment of common bile duct cancer in humans, we investigated the safety and effectiveness of endoscopic MCT with the assistance of intraductal ultrasonography (IDUS). We performed MCT in the canine small intestine as a model because of its similarity in size to the obstructed human common bile duct. Multiple coagulation lesions were made in anesthetized dogs, with the endoscope inserted through a jejunostomy. Under condition "A", the tip of the MCT probe was kept in a fixed position in contact with the mucosa of the intestine, and coagulation was performed with an output of 30 or 50 W for 30 or 10 s, respectively. Under condition "B", the tip of the MCT probe was moved along the intestinal mucosa, and coagulation was performed with an output of 50, 40, or 30 W, all for 10 s. After coagulation, a thin-caliber ultrasonic probe was inserted endoscopically for observation of the effects of coagulation. Each coagulation under condition "A" resulted in degeneration of all layers of the intestine. Coagulation under condition "B" resulted in more localized degeneration, extending from the mucosal layer to the proper muscle layer. By comparison with histologic observations, the accuracy of IDUS in assessing depth of degeneration was 87.5%. Endoscopic microwave coagulation was considered safe and effective, and IDUS was able to accurately assess the effects of microwave coagulation.

Animals↗

Limitations of three-dimensional intraductal ultrasonography in the assessment of longitudinal spread of extrahepatic bile duct carcinoma.

We investigated the utility and limitations of three-dimensional intraductal ultrasonography (3D-IDUS), for the assessment of the extent of longitudinal cancer spread to the hepatic side by extrahepatic bile duct carcinoma. In eight patients with extrahepatic bile duct carcinoma. 3D-IDUS was used to assess longitudinal cancer extension to the hepatic side prior to resection. When the linear dimension of 3D-IDUS showed bile duct wall thickening that was connected to the tumor and which became thin at a point, it was determined to be the front formation of longitudinal cancer extension. The findings were examined in relation to histologic information from the resected specimen. Although 3D-IDUS showed front formation of wall thickening in two patients, it accurately reflected the histological margin of the longitudinal cancer extension in only one patient. In the other patient, the wall thickening was longer than the histological margin. When 3D-IDUS showed bile duct wall thickening without front formation (n = 2), the wall thickening was longer than the histological margin of the longitudinal cancer extension. Even when 3D-IDUS did not show wall thickening (n = 4), one of these patients showed cancer spread histologically. As a result, the accuracy in assessing longitudinal cancer extension by 3D-IDUS was only 50%. Even if the linear dimension of 3D-IDUS demonstrated front formation of thickening of the bile duct, it reflected not only cancer extension but also inflammatory wall thickening.

Aged↗

Percutaneous recanalization of the bile duct along an endoscopic naso-biliary catheter.

Percutaneous recanalization of the bile duct is essential for placing biliary stents and carrying out other interventions. This prospective study was performed to establish safe approaches for percutaneous recanalization of the bile duct when it had previously resulted in failure. Between July 1995 and July 1999, percutaneous recanalization of the bile duct was attempted in 58 patients with a malignant biliary stenosis. When recanalization failed, an endoscopic naso-biliary drainage (ENBD) catheter was placed across the stenosis. The procedure was again attempted along the ENBD catheter. In the period of the study, four patients underwent successful recanalization after ENBD, although attempts prior to ENBD had been unsuccessful. As a result, the success rate of recanalization in the period was 100% (58/58). When recanalization fails, the use of an ENBD catheter may provide access to the biliary tree, and the biliary stenosis can be recanalized safely.

Abdominal Neoplasms↗

Placement of endoscopic naso-biliary drainage does not preclude subsequent percutaneous transhepatic biliary drainage.

We prospectively investigated whether the placement of endoscopic naso-biliary drainage (ENBD) precluded percutaneous transhepatic biliary drainage (PTBD). In 40 patients, the caliber of the intrahepatic bile duct was measured prior to ENBD by ultrasonography. When PTBD was required after ENBD, the ENBD catheter was clamped for 1 to 2 h before PTBD, and its caliber was again measured at the time of PTBD. When PTBD was performed within 7 days (mean, 1.8 days) after ENBD (n = 27), the size of the intrahepatic bile duct was 5.0 +/- 2.3 mm before and 4.6 +/- 2.3 mm after ENBD. There was no significant difference between these values (P > 0.5). When PTBD was performed 8 to 40 days (mean, 17.8 days) after ENBD (n = 13), the bile duct diameter was significantly reduced, from 4.2 +/- 1.5 mm (pre-ENBD) to 1.8 +/- 1.7 mm (post-ENBD) (P < 0.05). When PTBD was conducted within 7 days (mean, 1.8 days) after ENBD, previous ENBD did not induce collapse of the bile duct, if the ENBD catheter was clamped for 1 to 2 h before the puncture of the bile duct.

Bile Ducts, Intrahepatic↗

Interaction of Cytotoxic Bicyclic Peptides, Theonellamides A and F, with Glutamate Dehydrogenase and 17beta-Hydroxysteroid Dehydrogenase IV.

Theonellamide A, a bicyclic peptide isolated from a Theonella sponge, was fixed on hydrazide-containing gel beads and screened for its binding proteins from rabbit liver tissues. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that two major proteins of 80 kDa and 55 kDa interacted with theonellamide A. The interaction between theonellamide A and two proteins was confirmed by competition experiments in which these two proteins failed to bind to theonellamide A-conjugated gel beads in the presence of theonellamide A or F. Amino-terminal amino acid sequence analysis of peptide fragments derived from the binding proteins by lysylendopeptidase digestion demonstrated that the 80-kDa and 55-kDa proteins were 17beta-hydroxysteroid dehydrogenase IV and glutamate dehydrogenase, respectively. In an in vitro assay system, amination of alpha-ketoglutarate by glutamate dehydrogenase was activated with theonellamide F, although this effect was weaker than that with adenosine diphosphate, a well-known activator.

Journal Article↗