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Biomedical subjects

S Takeda

Publications and source records attributed to S Takeda.

At least 973 records · Page 54Linked to original sources
PubMedDate not supplied

Partial characterization of an immortalized human trophoblast cell-line, TCL-1, which possesses a CSF-1 autocrine loop.

Many previous studies in both mouse and human placenta have implicated a role for colony stimulating factor-1 (CSF-1) in the regulation of placental development. In this study we have examined CSF-1 production by an immortalized cell line (TCL-1) derived from the choriodecidua, transfected with a retrovirus gene coding for the large-T antigen. TCL-1 cells were uniformly positive by immunocytochemistry for the composite sub-units of human chorionic g gonadotrophin (hCG) but were negative for markers of other cell types localized at the fetal-maternal interface. Gelatinase enzymes were secreted by TCL-1 cells cultured on extracellular matrix in a manner indicative of extra-villous trophoblast. Dot-blot immunoassays and ELISA indicated that CSF-1 was secreted by TCL-1 cells, at levels comparable to primary trophoblast cells and BeWo choriocarcinoma (trophoblast tumour) cells. Reverse transcriptase-polymerase chain reaction analysis confirmed the presence in TCL-1 cells of CSF-1 receptor mRNA (c-fms gene product), indicating that the components of a potential autocrine loop were present in these cells. Proliferation of TCL-1 cells was not affected by the addition of exogenous CSF-1 but was elevated in response to treatment with a CSF-1 neutralizing antibody. The immortalized cell line, TCL-1, provides a potential model in which to investigate regulation of growth and differentiation of trophoblast cells in vitro.

Base Sequence↗
PubMedDate not supplied

Construction of chimaeric processed immunoglobulin genes containing mouse variable and human constant region sequences.

The specificity of monoclonal antibodies provides a powerful diagnostic and therapeutic tool in investigating human neoplasia. Radiological scanning and immunotherapy with mouse tumour-specific monoclonal antibodies have been applied to patients with some success, but a major problem is the neutralization of the mouse antibody induced by repeated administration of heterologous antibodies. To avoid or reduce such immune reactions, chimaeric immunoglobulins consisting of mouse variable (V) and human constant (C) regions can be synthesized. We have constructed a recombinant retrovirus DNA carrying genomic heavy-chain (H) variable-diversity joining (VH-D-JH) and C gamma 1 genes from different species and show here that the chimaeric intervening sequences are spliced out precisely. This procedure provides a useful method to construct the chimaeric mouse-human immunoglobulin gene to be expressed in Escherichia coli, yeast and animal cells. Unexpectedly, a hidden splice donor site in the 5'-flanking region of a human VH gene is used in place of the donor site of the leader sequence exon, resulting in the formation of the V region without the leader sequence.

Animals↗
PubMedDate not supplied

The role of disseminated intravascular coagulation in shock induced by transfusion of human blood in dogs.

Hemolytic blood transfusion reactions were produced in 20 dogs. Animals transfused with human blood twice in a two-week interval demonstrated a significant increase in anti-human red blood cell agglutination titer at the time of the second transfusion. Eighteen dogs that survived from the first transfusion reaction were divided into two groups with or without heparin treatment. The hemolytic transfusion reaction in the sensitized animals was characterized by shock and multiple coagulation abnormalities. Heparin failed to prevent shock, hemoglobinemia and thrombocytopenia, and decreased the mortality rate in heparinized animals. Pathologic examination revealed that the thrombi in the splanchnic organs were less common in the heparinized dogs.

Agglutination Tests↗
PubMedDate not supplied

Evaluation of organic solvent ototoxicity by the upper limit of hearing.

To clarify the effects of organic solvents on hearing, we measured the upper limit of hearing in 93 male workers exposed to organic solvents in 7 factories that produced plastic buttons or baths. Medical examinations, environmental monitoring (i.e., concentration in breathing-zone air), and biological monitoring (i.e., concentration in urine) of the organic solvents were also done. Although the organic solvent concentrations in the environmental monitoring were lower than the occupational exposure limit, the upper limit of hearing was reduced in workers who were exposed for 5 y or more. This reduction was dose-dependent and was related to styrene concentrations in breathing-zone air and mandelic acid concentrations in urine. Even individuals who had normal medical examinations showed a reduced upper limit of hearing. The upper limit of hearing may serve as an early detection indicator of health effects in workers constantly exposed to styrene.

Acetone↗
PubMedDate not supplied

Age variation in the upper limit of hearing and amplitude of eye accommodation in childhood and adolescence.

The upper limit of hearing and amplitude of eye accommodation were examined, and their standard aging curves were established in order to evaluate their age-related changes in childhood and adolescence. The subjects were 2497 audiometrically and otologically normal ears and 2349 optometrically and ophthalmologically normal eyes ranging in age from 5 to 24 years in Japan. The upper limit of hearing was measured by the equipment made by us. The amplitude of eye accommodation was calculated at near point and far point measured by the ophthalmodynamometer. Both the upper limit of hearing and amplitude of eye accommodation became gradually less as age increased. The variability of the upper limit of hearing was less than that of the amplitude of eye accommodation. Standard aging curves were established in childhood and adolescence by calculating 10th, 25th, 50th, 75th and 90th centiles. There is no significant relationship between the upper limit of hearing and the amplitude of eye accommodation.

Accommodation, Ocular↗
PubMedDate not supplied

Synchronous mucinous adenocarcinoma of the endometrium and mucinous cystadenoma of bilateral ovaries presenting during fertility therapy.

We describe a very rare case of synchronous mucinous tumor of the endometrium and ovaries presenting during ovulation induction. A 31-year-old woman received ovulation induction for 5-year primary infertility. Ultrasonography revealed mucus retention in the uterine cavity and bilateral multicystic ovaries during ovulation induction. Atypical hyperplasia was diagnosed by endometrial curettage. Repeated procedures including ovarian cystectomy, endometrial curettage and in vitro fertilization combined with progestine therapy resulted in no pregnancy but rapid recurrences. She finally underwent simple hysterectomy and bilateral salpingo-oophorectomy. Microscopic examination revealed mucinous cystadenoma in the both ovaries and well differentiated mucinous adenocarcinoma of the endometrium.

Adenocarcinoma, Mucinous↗
PubMedDate not supplied

Modification of cardiac subcellular remodeling due to pressure overload by captopril and losartan.

In view of the activation of renin-angiotensin system under conditions associated with pressure overload on the heart, we examined the effects of captopril, an angiotensin converting enzyme inhibitor, and losartan, an angiotensin II receptor antagonist, on cardiac function, myofibrillar ATPase and sarcoplasmic reticular (SR) Ca2+-pump (SERCA2) activities, as well as myosin and SERCA2 gene expression in hypertrophied hearts. Cardiac hypertrophy was induced in rats treated with or without captopril or losartan by banding the abdominal aorta for 8 weeks; sham operated animals served as control. Decrease in left ventricular developed pressure, +dP/dt and -dP/dt as well as increase in left ventricular end diastolic pressure and increased muscle mass due to pressure overload were prevented by captopril or losartan. Treatment of animals with captopril or losartan also attenuated the pressure overload-induced depression in myofibrillar Ca2+-stimulated ATPase, myosin ATPase, SR Ca2+-uptake and SR Ca2+-release activities. An increase in beta-myosin heavy chain mRNA and a decrease in alpha-myosin heavy chain mRNA as well as depressed SERCA2 protein and SERCA2 mRNA levels were prevented by captopril or losartan. These results suggest that both captopril and losartan improve myocardial function in cardiac hypertrophy by preventing changes in gene expression and subsequent subcellular remodeling due to pressure overload.

Angiotensin Receptor Antagonists↗
PubMedDate not supplied

Clinical significance of alpha-fetoprotein mRNA during perioperative period in HCC.

BACKGROUND/AIMS: The presence of alpha-fetoprotein (AFP)mRNA in the peripheral blood of patients with HCC suggested that carcinoma cells still existed. We investigated the influence of an alternation of human AFPmRNA perioperatively detected in peripheral blood in matters of recurrence, prognosis and operative performance. METHODOLOGY: Thirty-three patients with HCC were enrolled for this study. AFPmRNA in peripheral blood before the operation, and on 1, 3, 7, 14, 21 and 28 post-operative days was examined by means of the reverse-transcriptase polymerase chain reaction (RT-PCR). RESULTS: In 18 of 33 patients (54.5%) with HCC, AFPmRNA was detected in peripheral blood pre-operatively. Ten of 22 (45.4%) who were detected with AFPmRNA in peripheral blood during the perioperative period were diagnosed with intrahepatic recurrence or distant metastasis within 12 months post-operatively. In contrast, 10 (90.8%) of 11 patients who were not detected with AFPmRNA in peripheral blood anytime during hospitalization were diagnosed as free of intrahepatic recurrence or distant metastases within 9 months after the operation. CONCLUSIONS: These results suggested that an alternation of AFPmRNA from HCC patients' peripheral blood during the perioperative period by means of this technique may be a practical tool in the detection of early recurrence or distant metastases after surgery.

Adult↗
PubMedDate not supplied

Peritoneal washings cytology combined with immunocytochemical staining in pancreatic cancer.

BACKGROUND/AIMS: Peritoneal washings from patients with pancreatic cancer demonstrate malignant cells in 0-58% of patients. But the significance of their potential for implantation and growth after radical surgery has not been clarified. METHODOLOGY: Peritoneal washings were collected from 74 consecutive pancreatic cancer patients during a 5-year period and studied by conventional staining and immunocytochemical staining using anti-CEA and anti-CA 19-9. Fifty of the 74 patients were resectable and the others were nonresectable. RESULTS: Seven out of 8 patients with macroscopic peritoneal metastasis were positive in conventional staining, but all 8 patients were positive in immunocytochemical staining. Five of the 66 (8%) patients without macroscopic peritoneal metastasis were positive in conventional staining, but the positive rate increased to 14 of 66 (22%) in immunocytochemical staining. There was no statistically significant difference in post-operative cumulative survival rate between the 13 positive cytology patients and 37 negative cytology patients without macroscopic peritoneal metastasis. CONCLUSIONS: The positive rate of peritoneal washings cytology was increased in this study by the use of immunocytochemical staining in addition to conventional staining. No statistically significant difference in post-operative cumulative survival rate between positive cytology patients and negative cytology patients without macroscopic peritoneal metastasis was observed.

Adenocarcinoma↗
PubMedDate not supplied

A case of the development of two hepatocellular carcinomas and a cholangiocarcinoma with cirrhosis after elimination of serum hepatitis C virus RNA with interferon therapy.

A 64-year-old man who had exhibited abnormal transaminase levels for about 20 years was admitted to a hospital for the treatment of liver damage. Laboratory testing demonstrated that he was suffering from chronic hepatitis C, and a liver biopsy showed chronic active hepatitis with septal fibrosis. He was treated with interferon-alpha, and HCV-RNA became undetectable. Four years after the completion of interferon treatment, 3 lesions in the patient's liver were revealed by routine ultrasonography, and he was referred to Nagoya University Hospital for further examinations on November 1997. Radiographical examinations such as computed tomography and angiography demonstrated 2 hypervascular tumors (size: phi 35 mm and phi 20 mm) and 1 hypovascular tumor (phi 28 mm). Qualitative analysis for HCV-RNA by polymerase chain reaction method was negative. Partial hepatectomy was performed, and pathological examination of the tumors showed 2 moderately differentiated hepatocellular carcinomas and cholangiocarcinoma accompanied with liver cirrhosis. We propose that even patients with disappearance of HCV-RNA after interferon therapy, especially with liver cirrhosis or severe fibrosis, should be followed-up closely and examined at regular intervals because of the high risk of developing primary liver cancers.

Carcinoma, Hepatocellular↗
PubMedDate not supplied

PIVKA-II during perioperative period in patients with hepato-biliary-pancreatic diseases.

BACKGROUND/AIMS: In this study, we examined the influence of clinical treatments in the perioperative period upon PIVKA-II (plasma levels of protein induced by vitamin K absence or antagonist-II) in patients with hepatocellular carcinoma and pancreatobiliary diseases. METHODOLOGY: During a perioperative period, plasma PIVKA-II levels were measured in 144 patients with various hepatobiliary and pancreatic diseases by two types of EIA kit, using the conventional monoclonal antibody MU-3 and the new monoclonal antibody 19B7; Thrombotests were given at the same time. RESULTS: PIVKA-II of hepatocellular carcinoma patients showed higher reactivity with MU-3 than with 19B7. On the other hand, PIVKA-II of pancreatobiliary malignancies showed higher reactivity to 19B7 than it did to MU-3. In hepatocellular carcinoma patients, there was no correlation between PIVKA-II and Thrombotest levels; however, a significant correlation was found in patients with obstructive jaundice due to pancreatobiliary cancer. PIVKA-II levels decreased gradually to normal range within about 2 weeks after the curative operation. PIVKA-II levels in the patients receiving antibiotics containing N-methyl-thiotetrazole without administration of vitamin K remained high as long as the antibiotics were administered, but decreased to normal range as soon as the administration was finished. CONCLUSIONS: PIVKA-II which is produced by hepatocellular carcinoma may be different from that produced by obstructive jaundice due to pancreatobiliary malignancies. The clinical treatments in perioperative period, such as the administration of antibiotics containing N-methyl-thiotetrazole or vitamin K, readily influence PIVKA-II levels. Therefore, abnormal PIVKA-II levels must be carefully interpreted in the diagnosis of hepatocellular carcinoma and pancreatobiliary malignancies.

Adult↗
PubMedDate not supplied

Clinical usefulness of the immunostaining of the tumor markers in pancreatic cancer.

The effect of the rapid immunostaining of gastrointestinal cancer-associated antigens, CA19-9, CEA, DUPAN2, and CA50 was discussed for intraoperative pathological diagnosis of pancreatic cancer. The method can be completed in only 13 minutes with microwave irradiation to accelerate the incubation of the primary antibody. Only 3 seconds of irradiation at 500 W for fresh-frozen sections produced specific antigen staining of greater intensity than that obtained with longer incubation by the conventional method. Preservation of the tissue structure was satisfactory with minimal nonspecific background staining enabling us to diagnose the intrapancreatic spread of cancer. This method was also applied to intraoperative peritoneal washing cytology. As with frozen section biopsy, the sensitivity of intraoperative cytology is greater than by the conventional staining method, which is able to achieve more precise staging of pancreatic cancers. Our rapid immunoperoxidase staining method on the cryostat section of pancreatic biopsy specimens and on cytology samples provides important information to determine an appropriate operative approach for pancreatic cancer.

Adenocarcinoma↗
PubMedDate not supplied

Intraoperative diagnosis of pancreatic cancer extension using IVUS.

BACKGROUND/AIMS: Pancreatic cancer easily invades retroperitoneal tissue, especially the portal vein and extrapancreatic nerve plexus. We evaluated the diagnostic accuracy of intraportal endovascular ultrasonography in portal vein and extrapancreatic nerve plexus invasion. METHODOLOGY: Intraportal endovascular ultrasonography was performed in 78 cases of pancreatic cancer (head 67, body 8, total 3). Intraportal endovascular ultrasonography was performed intraoperatively from the superior mesenteric vein with an 8-French, 20-MHz intravascular ultrasound catheter. Three-dimensional intraportal endovascular ultrasonography was constructed by volume rendering. RESULTS: Intraportal endovascular ultrasonography visualized the portal vein as an echogenic band with a thickness of 0.5 mm to 1.0 mm. The diagnostic criterion of portal vein invasion was obliteration of this echogenic band. Intraportal endovascular ultrasonography visualized segment II of the extrapancreatic nerve plexus as the high-echoic area around the inferior pancreaticoduodenal artery. The diagnostic criterion of extrapancreatic nerve plexus invasion was low-echoic infiltration around the inferior pancreaticoduodenal artery. The sensitivity, specificity, and overall accuracy of intraportal endovascular ultrasonography for diagnosis of portal vein invasion was, respectively, 97.4%, 92.5%, and 94.9%. The values for diagnosis of extrapancreatic nerve plexus invasion, respectively, were 94.4%, 97.1%, and 96.2%. Three-dimensional intraportal endovascular ultrasonography depicted the invasion area as a defect of the portal vein wall. CONCLUSIONS: Intraportal endovascular ultrasonography detected subtle portal invasion and provided accurate portal invasion area which was useful for portal vein an reconstruction. Intraportal endovascular ultrasonography could also diagnose the extrapancreatic nerve plexus invasion of segment II.

Aged↗
PubMedDate not supplied

The role of extended radical operation for pancreatic cancer.

BACKGROUND/AIMS: To clarify the indication of extended operation for pancreatic carcinoma, a clinical study was carried out. METHODOLOGY: From July 1981 to 1999, 196 of 307 (63.8%) patients with pancreatic carcinoma underwent resection of the tumor. Portal vein resection was performed in 145 of these 196 (74.0%) resected cases. The postoperative survival rate was studied according to the operative and histopathological findings. RESULTS: In spite of the aggressive surgery, there was no patient who survived over 3 years after operation in the group carcinoma-positive on the surgical margins. Patients who survived over 3 years postoperatively were observed in the group of carcinoma-free surgical margins. CONCLUSIONS: The most important indication of extended operation combined with portal vein resection for pancreatic cancer is to obtain surgical cancer-free margins. There is no indication of extended operation for cases in which surgical margins will become cancer-positive, if such an operation is employed.

Constriction, Pathologic↗
PubMedDate not supplied

The role of adjuvant therapy for pancreatic cancer.

BACKGROUND/AIMS: In spite of radical pancreatectomy with lymphadenectomy for adenocarcinoma of the pancreas, survival remains poor. We add two forms of adjuvant therapy, i.e., intraoperative radiotherapy and liver perfusion chemotherapy, to the radical resection. The aim of this study is to investigate the utility of these two forms of adjuvant therapy prospectively and to review their effectiveness. METHODOLOGY: One hundred and ninety-six patients with pancreatic cancer who underwent radical pancreatectomy in our institute were enrolled. We conducted intraoperative radiation therapy 30 Gy against the retroperitoneal connective tissues around the superior mesenteric artery during surgery. Adjuvant liver perfusion chemotherapy was added immediately after operation via the portal vein using 5-fluorouracil (250 mg/body/day) for 3 to 4 weeks continuously. Overall survival analyses were done by the method of Kaplan and Meier. RESULTS: Intraoperative radiation therapy did not influence the prognoses directly. However, the patients who received adjuvant liver perfusion chemotherapy had better prognoses (P < 0.05). CONCLUSIONS: Although adjuvant therapy after radical resection with wide lymphadenectomy improves prognoses, the results are still not satisfactory. We should develop a new and more efficacious treatment.

Adenocarcinoma↗
PubMedDate not supplied

Gene therapy for pancreatic cancer.

Despite improvements in surgical care and locoregional therapy, the prognosis of patients with pancreatic cancer has seen little improvement over the last several decades. It is difficult to diagnose pancreatic cancer at its earliest stages when it is amenable to cure by surgical resection because it is too small to produce symptoms in the affected patient. Recent improvements in radiographic modalities aimed at earlier detection and extent of cancer spread have enabled the clinician to provide the most efficacious treatment regimen possible. Nevertheless, pancreatic cancer is very aggressive locally and frequently metastasizes to the liver and peritoneum. New strategies are necessary to treat pancreatic cancer and gene therapy offers hope in this regard. Many studies have revealed the promise of gene therapy in the treatment of pancreatic cancer in rodent models. Early clinical trials are ongoing to evaluate the success of these gene therapy regimens in humans. In this article we review the gene therapy strategies currently employed in the fight against pancreatic cancer, including antisense strategies, gene-directed prodrug activation therapy, promoter gene strategies, and oncolytic viral therapy.

Animals↗
PubMedDate not supplied

Surgical treatment of intraductal papillary-mucinous tumors of the pancreas.

BACKGROUND/AIMS: IPMT (Intraductal papillary-mucinous tumor of the pancreas) is increasingly recognized. The aim of this study was to investigate the appropriate surgical treatment for these tumors. METHODOLOGY: Between January 1981 and September 1998, 62 patients with IPMT underwent surgery. We retrospectively examined the clinicopathological features and surgical outcomes of the patients. RESULTS: The types of IPMT were as follows: hyperplasia (20); adenoma (31); and carcinoma, both invasive (5) and noninvasive (6). Lymph node metastasis was found in 36% of the carcinomas. The size of mural nodules was more than 3 mm in all adenoma or carcinoma cases, while the percentage of hyperplasia less than 3 mm was 75%. Intraoperative pancreatoscopy and annular array ultrasonography were very useful, because they detected 10 lesions that could not be found by preoperative examinations, such as computed tomography, endoscopic retrograde pancreatography, and endoscopic ultrasonography. All patients underwent surgical resection, including 10 pancreaticoduodenectomies (Whipple's procedure), 10 pylorus-preserving pancreaticoduodenectomies, 13 pancreatic head resections with segmental duodenectomies, 17 distal pancreatectomies, 9 segmental resections of the pancreas, 2 duodenum-preserving pancreatic head resections, and 1 total pancreatectomy. No operative or hospital death was observed. The postoperative survival rate at 5 years was 71.6% for carcinoma in IPMT. All of the cases with hyperplasia, adenoma and noninvasive carcinoma survived. Only two of the patients with invasive carcinoma died. CONCLUSIONS: IPMT had a favorable prognosis, as compared with pancreatic duct carcinoma. When selecting a surgical procedure for treating these tumors, it is important to confirm the tumor extent, as well as the diagnosis of invasion or noninvasion. In cases with invasion, radical resection is required. On the other hand, organ-function-preserving procedures should be selected for diseases without invasion.

Adult↗