The 10th Clinical Cancer Research Forum.
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Humans↗
Biomedical subjects
M Terada
Publications and source records attributed to M Terada.
The sera from GM1 ganglioside antibody positive patients with Guillain-Barré syndrome or chronic inflammatory demyelinating polyneuropathy blocks Na+ currents in rat single myelinated nerve fibers.
OBJECTIVE: To determine the possible role of anti-GM1 ganglioside antisera from patients with Gullain-Barr*e syndrome (GBS) or chronic inflammatory demyelinating polyneuropathy (CIDP) in the development of nerve dysfunction. METHODS: The effect of the anti-GM1 antibody positive antisera obtained from 4 GBS patients and 1 CIDP patient on membrane potential and ionic currents in rat single myelinated nerve fibers was investigated using the voltage clamp technique and compared with that of the anti-GM1 negative antisera obtained from 3 healthy controls and 2 GBS patients. RESULTS: In the presence of active complement, anti-GM1 positive antisera from 5 patients including 4 GBS patients and 1 CIDP patient significantly suppressed Na+ current more than anti-GM1 negative antisera. CONCLUSION: This study supports the notion that anti-GM1 antibody is one of the causative factors of conduction abnormality in GBS patients.
Adult↗
Evaluation of a new care system provided to diabetic patients in the outpatient clinic.
OBJECTIVE: Evaluation of metabolic states and chronic complications is essential for maintaining a high quality of care for diabetic patients. We have assessed the quality of care in routine outpatient clinics for diabetic subjects in our university hospital, and compared with those in a newly introduced standardized clinic to evaluate the new care system. METHODS: The quality of care was assessed by the chart review in 1995, and compared with those from 1996-1997 in the "Diabetes Follow-up Clinic" which is systematically designed for the standardized care. PATIENTS: The subjects were recruited among 860 patients who visited the outpatient clinic in July and August of 1995 with a diagnosis of diabetes or glucose intolerance. Six hundred seventy-two patients whose follow-up period had been more than 6 months with clinically diagnosed diabetes were used for the analysis. RESULTS: Laboratory tests such as determination of HbA1c, and serum levels of lipids and creatinine were performed in more than 90% of the patients in the routine outpatient clinics. However, ophthalmology referral, 24-hour urine collection for the determination of creatinine clearance and albumin excretion, and electrocardiograms were not well performed and were incompletely documented (40-60% of the patients within a previous year and 70-80% in the last 2 years). In the standardized "Diabetes Follow-up Clinic", only four out of 555 diabetic patients failed to collect their 24-hour urine, and all participants had ankle blood pressure measurements, nerve conduction study, and nylon monofilament tests, etc. Furthermore, more than 95% of the patients had funduscopic examinations by ophthalmologists as well as records of electrocardiogram. CONCLUSION: Introduction of the standardized "Diabetes Follow-up Clinic" may be one of the choices for increasing the quality of outpatient care and for the prevention of chronic diabetic complications.
Adult↗
Effect of aldose reductase inhibitor on cutaneous nerve fiber length in diabetic patients.
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Aldehyde Reductase↗
Analysis of hepatocellular carcinoma fed by internal thoracic artery
Purpose: The purpose of this study was to elucidate the clinical features of hepatocellular carcinoma (HCC) fed by the internal thoracic artery (ITA). Methods: In seven patients HCC fed by the ITA was confirmed by digital subtraction angiography. The number of previous transcatheter arterial embolization (TAE), the period from the first TAE to TAE of the ITA, tumor location, tumor size, and occlusion of the hepatic artery (HA) and other collateral vessels were explored in each case. Results: The HCCs were located in S4 of the liver (n = 5) and in S8 (n = 1) and were fed by the right ITA and one nodule in S2-3 was fed by the left ITA. Tumor size was 3-10 cm. The number of previous TAE of the HA ranged from 2 to 12. The period from the first TAE to TAE of the ITA was 3-53 months. Angiography of these patients showed occlusion of the HA in six cases, and of the extrahepatic collaterals including the inferior phrenic artery (IPA) in five cases, intercostal artery (ICA) in one case, and epicholedocal artery (EPA) in one case. Conclusion: The ITA often supplies HCC located in the anterior superior region of the liver under the diaphragm; there can be long-term survival with repeated TAE and occlusion of HA.
Journal Article↗
[Pulmonary outflow tract reconstruction with autologous tissue during the Ross procedure: right ventricular characteristics in mid-term follow-up].
BACKGROUND: The Ross procedure requires the interposition of prosthetic or homograft extracardiac conduits to establish ventricle-pulmonary artery connection (RV-PA). These materials usually require multiple reoperations because of conduit failure. To avoid the re-replacement of currently available conduits, usage of autologous tissue may be preferable to reconstruct RV-PA connection during the Ross procedure, especially in the pediatric age group. METHOD: Ten patients (mean age 8.7 years, range 2-23) with congenital aortic valve disease underwent the Ross procedure between June, 1996 and July, 1998. To establish RV-PA continuity, autologous aortic wall including aortic valve with a gusset of pericardial tissue was used in six patients, rolled pericardial conduit with fresh pericardial bicuspid valve in three and one direct anastomosis of pulmonary posterior wall onto the right ventricle with a fresh pericardial monocusp valved patch. All patient's postoperative courses were uneventful. All patients were followed up (mean follow-up period: 21.6 +/- 6.6 months) and postoperative right ventricular characteristics, cardio-thoracic ratio (CTR) on chest X-ray and pulmonary valve function were evaluated. RESULTS: Postoperative right ventricular end-diastolic volume, right ventricular ejection fraction and right ventricular end-diastolic pressure did not change significantly (RVEDV: 128 to 113% of normal, RVEF: 56.4 to 51.5%, RVEDP: 5.9 to 10.1 mmHg). Pulmonary regurgitation during follow-up was mild in six patients and moderate in four. However, CTR decreased significantly over time (preop.: 56.5% postop.: 58.5%, late period: 53.4%). CONCLUSION: Our results support the concept of the reconstruction of pulmonary outflow tract without foreign materials during the Ross procedure. Longer follow-up are necessary to define the possible limitation of this technique.
Adult↗
[Cancer therapy and processing information].
The National Cancer Center Japan started to provide free, computer-based cancer information, through a service called the National Cancer Center--Cancer Information Service (NCC-CIS), to patients and their families, physicians and other health professionals via fax (telephone) and the Internet in 1996. NCC-CIS in Japanese is modeled on the Physician Data Query service produced by the National Cancer Institute in the United States and is produced from an independent standpoint adopted to the medical and social environment in Japan. NCC-CIS provides up-to-date cancer treatment information (staging, prognosis and state-of-the-art treatment by stage of disease), supportive care for each type of cancer, an image reference database, and a directory of organizations and lecture meeting reports in Japan in order to facilitate better understanding of cancer among people and support the decision-making process for physicians in order to achieve a reduction in cancer deaths.
Humans↗
[Long-term results of TIPS].
The long-term results of transjugular intrahepatic portosystemic shunt(TIPS) were analyzed in 48 patients between February 1992 and December 1998, for treatment of esophageal varices and ascites caused by portal hypertension. The procedure was successful in 42 patients. Portal vein pressure was reduced from 29 mmHg +/- 7.9 to 19 mmHg +/- 7.3 immediately after TIPS and to 17 mmHg +/- 6.5 one year later. Varices were controlled in 82% (23/28) of patients after one year and in 78% (7/9) of patients after five years. Ascites disappeared or decreased in 79% (11/14) after one year. Primary shunt patency was 12%, with a secondary patency rate of 79% after five years. The overall incidence of new or worsened encephalopathy was 31% (13/42). Long-term follow-up showed one-, three-, and five-year survival rates of 82%, 68%, and 59%, respectively. TIPS is an effective means of lowering portal hypertension, and it controls varices and ascites with little risk of hepatic encephalopathy.
Adult↗
[Therapeutic effect of TAE in patients with hepatocellular carcinoma using color Doppler imaging with intravenous ultrasound contrast agent].
We evaluated the therapeutic effect of TAE in 9 nodules with hepatocellular carcinoma (HCC) using color Doppler flow imaging with an intravenous ultrasound contrast agent. The intratumoral color signal enhancement that was detected in 7 nodules resulted in complete disappearance after TAE. The other 2 nodules without color signal enhancement showed well-differentiated HCC with fatty degeneration on histological study. The intratumoral enhancement noted in dynamic MRI in 7 of the 9 nodules resulted in complete disappearance after TAE. Color Doppler flow imaging with an intravenous contrast agent is a promising method for assessing the therapeutic effect of TAE.
Aged↗
Transgenic rats carrying copies of the human c-Ha-ras proto-oncogene exhibit enhanced susceptibility to N-butyl-N-(4-hydroxybutyl)nitrosamine bladder carcinogenesis.
We have established a transgenic rat line carrying three copies of the human c-Ha-ras proto-oncogene with its own original promoter region, Jcl/SD-TgN(HrasGen)128Ncc (Hras128) rat. c-Ha-ras protein from expression of transduced and endogenous c-Ha-ras genes could be detected in the bladder epithelium of untreated transgenic rats. To examine their susceptibility to N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-induced urinary bladder carcinogenesis, male transgenic and wild-type littermates were treated with 0.05% BBN in their drinking water for 10 weeks and then killed at week 20. The numbers and volumes of total macroscopic bladder tumors including both transitional cell papillomas and carcinomas (TCC) per rat were much greater in Hras128 rats than in their wild-type counterparts. The numbers of carcinomas per rat were also significantly greater in Hras128 rats. Two cases of TCC exhibiting invasion of the bladder muscle layer, which is extremely rare in the wild-type animals under the experimental conditions used, were also observed in Hras128 rats. The GGC-->GAC mutations at codon 12 of the transgene were observed in only two TCC out of 21 bladder tumors (9.5%), assessed by RFLP analysis and direct sequencing. SSCP analysis did not show any endogenous c-Ha-ras gene mutations. One of 25 tumors (4.0%) in wild-type rats had an endogenous c-Ha-ras gene mutation at codon 12 that was detected (GGA-->GAA) by single-strand conformation polymorphism and direct sequencing. These results indicate that the Hras128 rat is highly susceptible to BBN carcinogenesis and may be utilized as a rat model for analysis of bladder tumor development. The mutation findings indicate that the enhanced tumor development is not primarily due to mutations occurring in the transgene.
Animals↗
[Cerebral oxygenation during non-blood prime cardiopulmonary bypass in congenital heart surgery].
To analyze oxygen delivery to the brain and cerebral cellular oxygenation during non-blood prime and blood prime cardiopulmonary bypass (CPB), 22 patients undergoing cardiac surgery with CPB were studied by near infrared spectroscopy (NIRS) monitor (NIRO 500, Hamamatsu Photonics). NIRS can assess continuously cytochrome oxidase (Cyt.aa 3) which is the terminal enzyme of the intramitochondrial respiratory chain. Patients were grouped according to conditions of CPB management: one group underwent repair with non-blood prime (group A, n = 12); the second group underwent with blood prime (group B, n = 10). Body weights ranged from 5.5 kg to 58 kg in group A, and 2.9 kg to 16 kg respectively. CPB was maintained at flow rates between 100 to 150 ml/kg/min. and the acid-base management strategy was alpha stat in all patients. No neurological complication was observed. NIRS date were expressed as changes from baseline where cannulation was prepared. The lowest value of Cyt.aa 3 was -2.7 +/- 0.7 mumol/l in the group A, and -3.9 +/- 1.0 mumol/l in the group B. From the standpoint of changes in Cyt.aa 3, non-blood prime cases we studied were speculated to be within a safety limit. In order to define the definite safety limits, however, further studies including the reduction velocity of Cyt.aa 3 signal as well as the absolute value of the lowest Cyt.aa 3 concentration are required.
Brain↗
[Heparin monitoring during cardiopulmonary bypass in congenital heart surgery].
The Hepcon/HMS system automatically provides the activated clotting time and a whole blood heparin concentration. It also provides the adequate protamine dose by titration of protamine to heparin. 45 patients undergoing congenital heart surgery with cardiopulmonary bypass (CPB) were studied by the Hepcon/HMS device. We measured the heparin dose response before heparin administration, and the ration between the dose of protamine (ml) which was necessary for heparin neutralization at the termination of CPB and the dose of total heparin (ml) in each patient. The value of heparin dose response ranged 120-390 (mean 228) IU/kg. The ratio between protamine dose and heparin dose varied 0.11-0.99 (mean 0.55). There was a statistically significant correlation between the duration of CPB and this ratio (r = -0.51, n = 45, p = 0.0005). From the standpoint of variances in the value of heparin dose response, conventional way of the heparin administration according to the patient's body weight alone may cause inadequacy of anticoagulation during CPB. A dose of protamine determined by Hepcon device that is smaller than a conventional dose of protamine prevents inadvertent overdose and, therefore, can reduce the adverse effects excessive protamine has.
Adolescent↗
Genetic basis of autoimmune disease in MRL/lpr mice: dissection of the complex pathological manifestations and their susceptibility loci.
MRL/MpJ-lpr/lpr (MRL/lpr) mice spontaneously develop various forms of autoimmune disease in the same individuals, including glomerulonephritis, polyarteritis, arthritis and sialoadenitis. An MRL recombinant congenic strain of mice bearing the gld gene, MRLiMpTn-gld/gld (MRL/gld), also develops lesions similar to those in MRL/lpr mice. The lpr and gld genes are a Fas deletion mutant and a Fas ligand mutant, respectively. Thus, autoimmune disease in these mice seemed to be a single gene disease involving the complex pathological manifestations as pleiotropy. However, comparative studies with C3H/HeJ and C57BL/6J strains of mice bearing lpr or gld revealed that these lesions developed only in mice with an MRL background. Moreover, these lesions were genetically segregated among MRL/lpr x (MRL/lpr x C3H/lpr)F1 mice. This indicates that an MRL strain has particular gene(s) affecting the development of each lesion. Association studies of each lesion with polymorphic microsatellite markers using backcross mice revealed that gene loci responsible for each lesion exist at different chromosomal positions and have additive and hierarchical properties of polygenic inheritance for some of the lesions. We conclude that the complex pathological manifestations of autoimmune disease are under the control of different combinations of polygenes.
Animals↗
Deletion of the carboxyl-terminal exons of K-sam/FGFR2 by short homology-mediated recombination, generating preferential expression of specific messenger RNAs.
The K-sam gene was first identified as an amplified gene from human gastric cancer cell line KATOIII, and its product is identical to fibroblast growth factor receptor 2. The K-sam gene is located on human chromosome 10q26 and is preferentially amplified in the poorly differentiated types, especially in the scirrhous type, of gastric cancers. During the course of studies on the structural characterization of the amplification units, we found that the carboxyl-terminal exons of K-sam were deleted in three of four of the scirrhous type of gastric cancer cell lines. These deletions generate preferential expression of mRNAs encoding K-sam proteins lacking the carboxyl-terminal region containing the tyrosine residues at positions 780, 784, and 813. The carboxyl-terminal region has been reported to have a sequence required for the inhibition of NIH3T3 transformation, indicating that cells with amplification of the truncated K-sam gene have a growth advantage during the carcinogenic process for the scirrhous type of gastric cancers. This is the first report showing the deletion of the carboxyl-terminal exons of the receptor-type of the protein tyrosine kinase gene. Sequence analysis of the DNA sequences surrounding the deletion junctions shows the presence of unique sequences and indicates the involvement of short homology-mediated recombination in the generation of these deletions.
3T3 Cells↗
Novel exons located more than 200 kb downstream of the previously described 3' exon of the K-sam gene for generating activated forms of KGF receptor.
The K-sam gene was first identified as an amplified gene in the poorly differentiated types, especially in the scirrhous type, of gastric cancers. We have recently found and reported that the carboxyl-terminal exons of K-sam are frequently deleted in the scirrhous type of gastric cancer. The deletion generates preferential expression of at least six novel K-sam-II mRNAs: K-sam-IIH1, -IIH2 and -IIH3/O4, and K-sam-IIO1, -IIO2, and -IIO3, which encode novel proteins lacking the transformation-inhibitory sequence or activated K-sam proteins. In this study, we investigated expression of the previously described K-sam-IIC1 and -IIC3 mRNAs and the novel six K-sam-II mRNAs in 14 gastric cancer cell lines, 7 breast cancer cell lines, and 20 human normal tissues. All the six novel K-sam-II mRNAs were expressed preferentially in the cell lines derived from the scirrhous type of gastric cancers but not in the 7 breast cancer cell lines and the 20 human normal tissues. We further determined the positional relationship of four exons of H1, O1, O2, and O3 out of the six exons of H1, H2, H3/O4, O1, O2, and O3, and found that these four novel K-sam exons were located more than 200 kb downstream of the previously described carboxyl-terminal exon of the K-sam gene. Expression of K-sam-IIH1, -IIO1, and -IIO2 mRNAs encoding activated K-sam products in the scirrhous type of gastric cancer cell lines HSC39, OCUM2M, HSC59, and HSC60 was not due to the deletion of the C1 exon of K-sam.
Amino Acid Sequence↗
Identification of genes showing differential expression in antisense K-ras-transduced pancreatic cancer cells with suppressed tumorigenicity.
K-ras point mutation occurs in >80% of pancreatic cancer. We reported previously that the transduction of an antisense K-ras RNA expression vector suppressed the growth of pancreatic cancer cells with K-ras point mutations in vitro and in vivo. The RNA differential display method (DD) was used to compare the mRNA expression profile of the pancreatic cancer cell line AsPC-1 and that of the antisense K-ras-transduced, growth-retarded AsPC-1 cells. cDNA fragments were isolated from 20 bands on the DD gel, and their differential expression between the two cell lines was confirmed. A sequence analysis revealed that all of the 11 clones up-regulated in the antisense-transduced cells were mitochondrial genes. The other nine cDNA clones that were down-regulated in the antisense-transduced AsPC-1 cells included an oncogene PTI-1 (prostate tumor inducing gene-1), matrix metalloproteinase (MMP)-7, the beta3 chain of laminin-5, lysosome-associated membrane protein-2, the H chain of apoferritin, ribosomal protein S6, proteasome subunit XAPC7, and two cDNA fragments with no homology to the GenBank database. In addition to the AsPC-1 cells, reverse transcription-PCR analysis on surgical specimens of pancreatic cancer revealed that the PTI-1 and MMP-7 genes were overexpressed in three and four cases, respectively, of five cases examined. This method offers a unique opportunity to identify a set of genes that may be modulated by K-ras activation, at least in a subset of the pancreatic cancer. The information on such genes may facilitate our understanding of the spectrum of the functional genetic changes in pancreatic cancer.
Blotting, Northern↗
Adenovirus-mediated transfer of HST-1/FGF-4 gene protects mice from lethal irradiation.
Intraperitoneal injection of a replication-deficient adenovirus containing the HST-1 (FGF-4) gene (Adex1HST-1) increased peripheral platelet counts in mice, and also effectively prevented experimentally induced thrombocytopenia. Here, we report the therapeutic potential of Adex1HST-1 on severely injured mice after exposure to otherwise lethal irradiation. Eighteen out of 20 mice that received Adex1HST-1 prior to gamma-irradiation (9 Gy) survived, while all the 20 mice with prior administration of control adenoviruses died after irradiation (P<0.0001). Hematological and histopathological analyses revealed that Adex1HST-1 acts as a potent protector against lethal irradiation, which causes injury of intestinal tract as well as myelosuppression in the bone marrow and spleen. These data demonstrate that the protective effects of administration of Adex1HST-1 against irradiation are superior to any other protective effects of cytokines against a lethal dose of irradiation, and that the pre-administration of Adex1HST-1 may be useful for lessening the side effects of currently used chemo- and radio-therapy against cancer.
Adenoviruses, Human↗
Plausible phosphoenolpyruvate binding site revealed by 2.6 A structure of Mn2+-bound phosphoenolpyruvate carboxylase from Escherichia coli.
We have determined the crystal structure of Mn2+-bound Escherichia coli phosphoenolpyruvate carboxylase (PEPC) using X-ray diffraction at 2.6 A resolution, and specified the location of enzyme-bound Mn2+, which is essential for catalytic activity. The electron density map reveals that Mn2+ is bound to the side chain oxygens of Glu-506 and Asp-543, and located at the top of the alpha/beta barrel in PEPC. The coordination sphere of Mn2+ observed in E. coli PEPC is similar to that of Mn2+ found in the pyruvate kinase structure. The model study of Mn2+-bound PEPC complexed with phosphoenolpyruvate (PEP) reveals that the side chains of Arg-396, Arg-581 and Arg-713 could interact with PEP.
Animals↗