Usefulness of a combination of machine perfusion and pentoxifylline for porcine liver transplantation from non-heart-beating donors with prolonged hypotension.
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Adenosine↗
Biomedical subjects
T Nemoto
Publications and source records attributed to T Nemoto.
Evaluation of the factors related to early graft function in 90 kidney transplants from non-heart-beating donors.
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Adolescent↗
Usefulness of continuous hypothermic perfusion preservation for renal grafts from non-heart-beating donors with prolonged warm ischemia time.
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Heart Arrest↗
Isoform-specific monoclonal antibodies against HSP90.
The purpose of this study was to develop monoclonal antibodies (mAbs) that distinguish between the two isoforms of human 90-kDa heat shock protein (HSP90), i.e., HSP90 alpha and beta. Human HSP90 alpha and beta isoforms expressed in Escherichia coli were separately used as antigens for developing the mAbs. Twenty-three and ten mAbs were obtained by immunization of mice with HSP90 alpha and beta, respectively. Among them, ten and three mAbs specifically recognized HSP90 alpha and beta isoforms, respectively, on the criteria of both enzyme-linked immunosorbent and immunoblotting analyses. Immunochemical analysis by use of the mAbs revealed that both of the HSP90 isoforms were present in human cells even under unstressed conditions and that the expression of HSP90 alpha was more strongly induced when the cells were exposed to arsenate. This is the first report of the development of the mAbs discriminating between the two isoforms of HSP90. The mAbs specific for HSP90 isoforms should be useful for the regulational and functional analyses of HSP90 isoforms.
Animals↗
Epitope-defined monoclonal antibodies against type-IV collagen for diagnosis of Alport's syndrome.
BACKGROUND: Alport's syndrome can be diagnosed by staining the alpha 5 chain of type IV collagen in kidney biopsy specimens with a monoclonal antibody. Because antibodies already established against the alpha 5 chain require denaturation treatment of cryostat sections to expose their epitopes. To save time and effort for staining, a new epitope-defined monoclonal antibody whose epitope is initially exposed on the surface of the molecule was established. METHODS: Two monoclonal antibodies against the triple-helical domains of the type IV collagen alpha 2 and alpha 5 chains were established with synthetic peptides as immunogens by the rat lymph node method. Their epitope were EAIQP at the positions of 675-679 of the alpha 2 chain, and IDVEF at the positions of 251-255 of the alpha 5 chain, respectively. They were purified with synthetic peptide-coupled affinity columns, and then conjugated with Texas red and FITC, respectively. RESULTS: The mixture of fluorochrome-conjugated antibodies was able to detect the distribution of the alpha 2 and alpha 5 chains in the normal and Alport kidney and skin by direct immunofluorescence staining with and without denaturation treatment of the sections. CONCLUSIONS: The direct double immunofluorescence staining of kidney and skin cryostat sections with the fluorochrome-conjugated antibodies is useful, reliable, and convenient for diagnosis of Alport's syndrome.
Amino Acid Sequence↗
Overexpression of protein tyrosine kinases in human esophageal cancer.
Using a PCR-based cloning technique, we isolated a series of protein tyrosine kinases (PTKs) expressed in a cell line of esophageal squamous cell carcinoma. Sequence analysis revealed 10 different kinds of PTKs of the receptor type [epidermal cell growth factor receptor, insulin-like growth factor I receptor, fibroblast growth factor receptor 4, eck, erk, discoidin domain receptor (DDR)/trkE/cell adhesion kinase (Cak), HEK2, HEK8, axl and sky] and one PTK of the nonreceptor type (tyk2). Subsequently, we examined the expression of the transcripts of these 11 genes in paired samples of normal and carcinomatous esophageal tissues obtained from 12 cases of esophageal cancer. We found that all 11 gene transcripts were expressed in both carcinomatous and normal tissues, and 6 of them were significantly overexpressed in carcinomatous tissues relative to adjacent normal tissues. Among these, the magnitude of mRNA expression of DDR/trkE/Cak PTK was positively correlated with the proliferative activity of carcinoma cells, but not with their degree of differentiation. Immunohistochemically, DDR was expressed in both normal and cancerous esophageal cells. The intensity of the expression was higher in cancer than normal tissue. In addition, we confirmed the expression of two isoforms of DDR/trkE/Cak in normal and cancerous esophagus. Our study suggests that DDR/trkE/Cak plays an important role in the regulation of proliferation of esophageal cancer.
Amino Acid Sequence↗
Angiotensin-converting enzyme gene polymorphism adds risk for the severity of coronary atherosclerosis in smokers.
To investigate the relation between the angiotensin-converting enzyme (ACE) gene polymorphism and acute coronary syndromes with respect to environmental factors, we analyzed the association of genotype with the coronary angiographic findings of patients with acute myocardial infarction or unstable angina pectoris, and we examined the linkage of each genotype with established risk factors for coronary artery disease. We determined the ACE genotype in 152 Japanese patients with acute coronary syndromes and 399 healthy individuals. The genotype distributions were not different between the two groups (P=.74, chi2 test). In the former group, coronary angiograms were evaluated by criteria based on the number of diseased vessels, the number of stenotic lesions (> or = 50%), and the relative abnormal arterial portion (extent index). Although the number of stenotic lesions was higher in patients with the DD genotype than in those with the ID or II genotype (P=.006), there were no differences in the number of diseased vessels or the extent index. When only smokers were analyzed, the number of diseased vessels (P=.032), number of stenotic lesions (P=.003), and extent index (P=.019) were all higher in patients with the DD genotype than in those with the ID or II genotype. In contrast, these differences in the respective parameters did not exist in nonsmokers. The results indicate smoking-associated effects of the ACE genotype on the severity of coronary atherosclerosis.
Coronary Artery Disease↗
[Plasma cell leukemia with amyloid deposition and osteogenetic change at the site of an extramedullary plasmacytoma].
A 49-year-old man was admitted with swelling in the left lower extremity, and a mass in the left lower abdomen. Laboratory findings showed an increased WBC of 15,000/microliter with 41% plasma cells, and immunoglobulin (Ig) A of 2,557mg/dl with a monoclonal component. A roentgenogram and computed tomograph of the abdomen revealed that a 5 x 10 cm mass with calcification located in the iliopsoas muscle. Plasma cell leukemia with extramedullary plasmacytoma was diagnosed, and the patient was treated with high-dose dexamethasone (40 mg/day for 4 days), resulting in a good response with the disappearance of plasma cells in peripheral blood and a marked decrease in serum Ig A. However, the patient's condition deteriorated in spite of various treatments, and he died of heart failure 5 months after admission. With informed consent from relatives, a necropsy was performed and infiltration of plasma cells in the mass in the iliopsoas muscle was noted. We reported this case because plasma cell leukemia with amyloid deposition and osteogenesis at the site of extramedullary plasmacytoma is very rare.
Amyloid↗
[Hyperparathyroidism, hypoparathyroidism].
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Humans↗
Expression of retinoid X receptors and COUP-TFI in a human salivary gland adenocarcinoma cell line.
The growth of the adenocarcinoma cell line derived from human salivary gland (HSG) is regulated by all-trans-retinoic acid (t-RA), which binds to its specific receptor, retinoic acid receptors (RARs), located in the nucleus, and thereby transactivates target genes. In this study, we examined the binding characteristics of the nuclear extract of HSG cells to the retinoic acid response element (RARE) compared with those of in vitro translated RAR alpha and retinoid X receptor alpha (RXR alpha), a heterodimeric partner of RAR alpha. Gel shift analysis using anti-RAR alpha and anti-RXR alpha antibodies revealed that the translated RAR alpha bound to RARE as a heterodimer with RXR alpha. In contrast, the binding of the nuclear extract of HSG cells to RARE showed a heterogeneous pattern, suggesting the existence of several species of RXRs as well as RARs in the nuclei of HSG cells. We therefore tried to clone these putative RXRs by the polymerase chain reaction using degenerated oligonucleotide primers conserved across the RXR family. The DNA sequencing of the recombinant clones revealed the expression of RXR alpha and RXR beta. In addition, chicken ovalbumin upstream promoter-transcription factor I (COUP-TFI), which is also an RXR family member, was cloned. To evaluate the transcriptional activity of RARs and RXRs endogenously expressed in HSG cells, we performed a transient transfection analysis. When HSG cells were transfected with a luciferase reporter plasmid containing two repeats of either the RARE of the RAR beta gene or that of cellular retinol-binding protein II gene, positioned upstream of a thymidine kinase promoter fused to the luciferase sequence, a 2-3-fold induction of luciferase activity was observed in both cases. These results suggest that RARs and RXRs endogenously expressed in HSG cells were transcriptionally active in vivo. Thus, our findings showed that RXR alpha, RXR beta, and COUP-TFI are expressed in HSG cells and suggest that these molecules function as heterodimeric partners of RARs and (or) competitive repressors for RAREs and are involved in cellular responses mediated by retinoids.
Adenocarcinoma↗
Cigarette smoking, N-acetyltransferase 2 genetic polymorphisms, and breast cancer risk.
OBJECTIVE: To determine if N-acetyltransferase 2 (NAT2) polymorphisms result in decreased capacity to detoxify carcinogenic aromatic amines in cigarette smoke, thus making some women who smoke more susceptible to breast cancer. DESIGN: Case-control study with genetic analyses. DNA analyses were performed for 3 polymorphisms accounting for 90% to 95% of the slow acetylation phenotype among whites. SETTING AND PARTICIPANTS: White women with incident primary breast cancer (n=304) and community controls (n=327). RESULTS: Neither smoking nor NAT2 status was independently associated with breast cancer risk. There were no clear patterns of increased risk associated with smoking by NAT2 status among premenopausal women. In postmenopausal women, NAT2 strongly modified the association of smoking with risk. For slow acetylators, current smoking and smoking in the distant past increased breast cancer risk in a dose-dependent manner (odds ratios [95% confidence intervals] for the highest quartile of cigarettes smoked 2 and 20 years previously, 4.4 [1.3-14.8] and 3.9 [1.4-10.8], respectively). Among rapid acetylators, smoking was not associated with increased breast cancer risk. CONCLUSIONS: Our results suggest that smoking may be an important risk factor for breast cancer among postmenopausal women who are slow acetylators, demonstrate heterogeneity in response to carcinogenic exposures, and may explain previous inconsistent findings for cigarette smoking as a breast cancer risk factor.
Adult↗
Premenopausal breast cancer risk and intake of vegetables, fruits, and related nutrients.
BACKGROUND: Given the international variations in breast cancer incidence rates and the changes in breast cancer incidence among migrant populations, it has been hypothesized that diet is a factor influencing risk of this disease. Many studies indicate that a diet high in vegetables and fruits may protect against breast cancer. PURPOSE: We conducted a case-control study of diet, including the intake of non-food supplements, and premenopausal breast cancer risk. We evaluated in detail usual intake of vegetables and fruits (each measured as the total reported grams consumed for all queried vegetables and fruit), vitamins C and E, folic acid, individual carotenoids, and dietary fiber with its components. METHODS: Case patients (n=297) were identified through pathology records from hospitals in Erie and Niagara counties in western New York. They consisted of premenopausal women 40 years of age or oder who were diagnosed with breast cancer from November 1986 through April 1991. Control subjects (n=311), frequency-matched to case patients on the basis of age and county of residence, were randomly selected from New York State Department of Motor Vehicles records. In-person interviews included detailed reports of usual diet in the period 2 years before the interview. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: There was a reduction in risk associated with high intake of several nutrients. With the lowest quartile of intake as the referent, adjusted ORs for the highest quartile of intake for specific nutrients were as follows: vitamin C (OR=0.53; 95% CI=0.33-0.86), alpha-tocopheral (OR=0.55; 95% CI=0.34-0.88), folic acid (OR=0.50; 95% CI=0.31-0.82), alpha-carotene (OR=0.67; 95% CI=0.42-1.08) and beta-carotene (OR=0.46; 95% CI=0.28-0.74), lutein + zeaxanthin (OR=0.47; 95% CI=0.28.0-77), and dietary fiber from vegetables and fruits (OR=0.48; 95% CI=0.30-0.78). No association with risk was found for beta-cryptoxanthin, lycopene, or grain fiber. Fruits were weakly associated with a reduction in risk (fourth quartile OR=0.67; 95% CI=0.42-1.09). No association was found between breast cancer risk and intake of vitamins C and E and folic acid taken as supplements. A strong inverse association between total vegetable intake and risk was observed (fourth quartile OR=0.46; 95% CI=0.28-0.74). This inverse association was found to be independent of vitamin C,alpha-tocopherol, folic acid, dietary fiber, and alpha-carotene. Adjusting for beta-carotene or lutein + zeaxanthin somewhat attenuated the inverse association with vegetable intake. CONCLUSIONS: In this population, intake of vegetables appears to decrease premenopausal breast cancer risk. This effect may be related, in part, to beta-carotene and lutein + zeaxanthin in vegetables. It appears, however, that, of the nutrients and food components examined, no single dietary factor explains the effect. Evaluated components found together in vegetables may have a synergistic effect on breast cancer risk; alternatively, other unmeasured factors in these foods may also influence risk.
Adult↗
A cytochrome P4502E1 genetic polymorphism and tobacco smoking in breast cancer.
Known breast-cancer risk factors account for only part of the variability in breast-cancer incidence. Tobacco smoke is not commonly considered a breast carcinogen, but many of its constituents, such as N-nitrosamines, are carcinogenic in laboratory animal studies. Herein, we assessed a cytochrome P4502E1 (CYP2E1) genetic polymorphism (a Dral restriction enzyme site in intron 6) as a risk factor for breast cancer in both premenopausal and postmenopausal women. Because N-nitrosamines are metabolically activated by CYP2E1, the risk among women smokers was investigated. Caucasian women were enrolled in a case-control study of breast cancer between 1986 and 1991. A subset of the women (219 premenopausal and 387 postmenopausal women) consented to phlebotomy. The allelic frequencies for the premenopausal women (D allele = 0.91 and C allele = 0.09) and postmenopausal women (D allele = 0.93 and C allele = 0.07) were similar to those previously reported. There was no statistically significant association between the CYP2E1 polymorphism and breast-cancer risk for premenopausal or postmenopausal women (adjusted odds ratio (OR) = 1.04, 95% confidence interval (CI) = 0.48, 2.24, and OR = 1.01, 95% CI = 0.55, 1.84, respectively). When the women were categorized as nonsmokers versus smokers (those who smoked more than one cigarette per week for more than 1 yr), premenopausal women with one or two C alleles who had a history of smoking were found to be at increased risk (unadjusted OR = 7.00, 95% CI = 0.75, 14.53, and adjusted OR = 11.09, 95% CI = 1.51, 81.41), although the number of study subjects with those genotypes was small. The small number of study subjects with a C allele precluded meaningful classification by level of smoking, but categorizing the smokers into two groups (above and below the median) also suggested an increased risk. Premenopausal women with the DD genotype and postmenopausal women with any genotype were not at increased risk. Breast-cancer risk was not related to the CYP2E1 genotype in either premenopausal nonsmokers or smokers (adjusted OR = 0.66, 95% CI = 0.20, 2.17, and OR = 2.13, 95% CI = 0.60, 7.59, respectively) or postmenopausal nonsmokers or smokers (OR = 0.90, 95% CI = 0.34, 2.35, and OR = 1.02, 95% CI = 0.46, 2.23, respectively), although the difference in the ORs for premenopausal nonsmokers and smokers suggests an increased risk for smokers. While there are limitations to this study, particularly related to the small number of subjects with the DC and CC genotypes, the study suggests that some women may be susceptible to tobacco smoke because of a CYP2E1 polymorphism. However, these results are preliminary and must be replicated.
Adult↗
Giant epiphrenic diverticulum with achalasia occurring 20 years after Heller's operation.
We report a case of giant epiphrenic diverticulum in a 43-year-old woman who underwent Heller's myotomy because of achalasia 20 years earlier. She complained of heartburn and dysphagia from March of 1991 and was hospitalized in our institution. An upper gastrointestinal X-ray examination with contrast medium revealed a large hemispheric lesion (7.8 x 4.8 cm) occupying the right posterior wall of the lower thoracic and abdominal esophagus. Manometry revealed a motility disorder and high pressure of the lower esophageal sphincter due to achalasia. Therefore she was diagnosed as having a giant diverticulum with achalasia after Heller's operation. She underwent transhiatal esophagectomy and reconstruction with placement of a gastric tube on June 4, 1992. Pathology results on the resected specimen revealed a false diverticulum. She has been doing well for 4 years since the operation. It has been said that a complication of incomplete long myotomy causes pulsion diverticulum, but we could not find a case of epiphrenic diverticulum after myotomy for achalasia reported in the literature in the last 10 years.
Diverticulum, Esophageal↗
Splint therapy for trigger thumb and finger in children.
Forty-three trigger thumbs and fingers in 33 children (15 boys and 18 girls, average age 2 years and 4 months) were treated using a polyethylene splint. Affected digits included 40 thumbs, one index finger, and two middle fingers. The IP joint was stabilized in maximum extension via a strap on the dorsal side. The splint was applied only at night and during day-time naps. Twenty-four digits recovered completely in an average of 10 months, seven digits improved, and two digits required surgery. Eight patients (10 digits) dropped out of treatment. Splint therapy is effective in treating trigger thumbs and fingers in children.
Child, Preschool↗
Herbimycin A down-regulates messages of cyclin D1 and c-myc during erythroid differentiation of K562 cells.
The ansamycin antibiotic, herbimycin A, is a potent tyrosine kinase inhibitor, and induces the erythroid differentiation of bcr-abl-possessing K562 cells. The growth of K562 cells was cytostatically reduced to less than 50% of the control level at 48 h by 0.5 microgram/ml of herbimycin A treatment. A total of 12% and 53% of the treated cells were benzidine-positive at 24 h and 48 h, respectively. The percentage of cells in the S phase decreased rapidly from 60% to 15% after 12 h of treatment. The reduction of S phase cells persisted until 24 h, whereas the G1 population conversely increased. Then underphosphorylated retinoblastoma gene product increased from 6 h to 24 h, but returned to baseline at 48 h. Most cell cycle controlling genes were unchanged by herbimycin A treatment. However, both cyclin D1 and c-myc were prominently down-regulated in the early phase of treatment, corresponding to the decline of the S phase population. Cyclin D1 was initially down-regulated to an undetectable level at 6 h, although its expression recovered gradually from 12 h and returned to baseline at 24 h. c-myc was also down-regulated from 1 h to 6 h. These data suggest that signals originating from bcr-abl kinase are at least partly transduced through both c-myc and cyclin D1, and that herbimycin A-induced erythroid differentiation occurs during or after the cessation of growth due to interference with these signals.
Antibiotics, Antineoplastic↗
Clonal identification of Burkitt's lymphoma arising from lymphocyte-predominant Hodgkin's disease.
The occurrence of large cell lymphomas subsequent to, or concurrent with, lymphocyte predominant Hodgkin's disease (LPHD) is a well-documented phenomenon. We present a case of Burkitt's lymphoma of the bladder, occurring after the successful treatment of LPHD of a cervical lymph node. To evaluate the clonal relationship of the two tumours, we amplified the complementarity-determining-region 3 of two samples from paraffin-embedded slides, using the polymerase chain reaction (PCR). The sequences of the PCR products showed 96% homology to each other. These results indicate that the malignant clone of Burkitt's lymphoma arose from the corresponding LPHD.
Aged↗
The regulatory subunits of fission yeast protein phosphatase 2A (PP2A) affect cell morphogenesis, cell wall synthesis and cytokinesis.
BACKGROUND: Protein phosphatase 2A (PP2A) holoenzymes have a trimeric structure, consisting of a catalytic subunit C and two regulatory subunits A (PR65) and B (PR55). In fission yeast the C subunits, being 80% identical to their mammalian counterparts, are essential for viability and negatively regulate the entry into mitosis. Genetic analyses in budding yeast and Drosophila show that the regulatory subunits are implicated in chromosome segregation, cell morphogenesis and/or cytokinesis. RESULTS: We isolated fission yeast genes paa1+ and pab1+ encoding the regulatory subunits PR65 and PR55, respectively. Gene disruption showed that the paa1+ gene was essential for viability while pab1+ was not required at 26-33 degrees C. Microtubule and actin distributions were anomalous in gene disrupted delta paa1 cells which were incapable of forming a polarized cell shape. Gene disrupted delta pab1 cells were pear- or round-shaped, and lost the polar distributions of actin and microtubules. In addition, delta pab1 cells were defective in cell wall synthesis and sporulation at permissive temperatures. At restrictive temperatures, delta pab1 cells showed an osmoremedial temperature-sensitive phenotype and delayed in cytokinesis. However, chromosome segregation was normal. CONCLUSION: Fission yeast PP2A regulatory subunit plays a critical role in cell morphogenesis, probably through regulation of the cytoskeletal network and cell wall synthesis.
Amino Acid Sequence↗