Biomedical subjects
Publications and source records attributed to W Ye.
A population-based cohort study of 36 856 women diagnosed with alcoholism in Sweden between 1965 and 1995 found that alcoholic women had only a small 15% increase in breast-cancer incidence compared to the general female population. It is therefore apparent, contrary to expectation, that alcoholism does not increase breast-cancer risk in proportion to presumed ethanol intake.
The purpose of this study was to examine the activation, topographic distribution, and cellular location of three mitogen-activated protein kinases (MAPKs) after permanent middle cerebral artery occlusion (MCAO) in mice. Phosphorylated MAPKs expression in the ischemic region was quantified using Western blot analysis and localized immunohistochemically using the diaminobenzide staining and double-labeled immunostaining. Extracellular signal-regulated kinases 1 and 2 (ERK1 and ERK2), p38 mitogen-activated protein (p38), and c-Jun NH2-terminal kinase or stress-activated protein kinase (SAPK/JNK) were initially activated at 30 minutes, 10 minutes, and 5 minutes, respectively, after focal cerebral ischemia. Peak expression represented a 2.7-fold, 3.7-fold, and 4.8-fold increase in each of these MAPKs, respectively. The immunohistochemical expressions of ERK1, ERK2, p38, and SAPK/JNK protein paralleled the Western blot analysis results. Double-labeled immunofluorescent staining demonstrated that the neurons and astrocytes expressed ERK1, ERK2, p38, and SAPK/JNK during the early time points after MCAO. The current results demonstrate that brain damage after ischemia rapidly triggers time-dependent ERK1, ERK2, p38, and SAPK/ JNK phosphorylation, and reveals that neurons and astrocytes are involved in the activation of the MAPK pathway. This very early expression of MAPKs suggests that MAPKs may be closely involved in signal transduction during cerebral ischemia.
PURPOSE: Immediate complete axillary lymphadenectomy (ALND) after sentinel lymphadenectomy (SLND) has confirmed that tumor-negative sentinel nodes accurately predict tumor-free axillary nodes in breast cancer. Therefore, we hypothesized that SLND alone in patients with tumor-negative sentinel nodes would achieve axillary control, with minimal complications. PATIENTS AND METHODS: Between October 1995 and July 1997, 133 consecutive women who had primary invasive breast tumors clinically </= 4 cm in diameter and no axillary lymphadenopathy were prospectively entered onto a trial of SLND using vital blue dye. Sentinel nodes were examined by standard microscopy or immunohistochemistry. SLND was the only axillary surgery if sentinel nodes were tumor-free. Completion ALND was performed only if sentinel nodes contained metastases or if they were not identified. Excluded from subsequent analysis were patients with unsuspected multifocal carcinoma and those who refused completion ALND. The complication and axillary recurrence rates after SLND without ALND were determined. RESULTS: Sentinel nodes were identified in 132 (99%) of 133 patients. Eight patients were excluded from further analysis. Of the 125 assessable patients, 57 had tumor-positive sentinel nodes and one had an unsuccessful mapping procedure; these patients underwent completion ALND. In the remaining 67 patients (54%), SLND was the only axillary procedure. Complications occurred in 20 patients (35%) undergoing ALND after SLND but in only two patients (3%) undergoing SLND alone (P =.001). There were no local or axillary recurrences at a median follow-up of 39 months. CONCLUSION: Complication rates are negligible after SLND alone. An absence of axillary recurrences supports SLND as an accurate staging alternative for breast cancer and suggests that routine ALND can be eliminated for patients with histopathologically negative sentinel nodes.
In order to investigate an association between residential radon exposure and risk of lung cancer, a case-control study was conducted in Misasa Town, Tottori Prefecture, Japan. The case series consisted of 28 people who had died of lung cancer in the years 1976-96 and 36 controls chosen randomly from the residents in 1976, matched by sex and year of birth. Individual residential radon concentrations were measured for 1 year with alpha track detectors. The average radon concentration was 46 Bq/m3 for cases and 51 Bq/m3 for controls. Compared to the level of 24 or less Bq/m3, the adjusted odds ratios of lung cancer associated with radon levels of 25-49, 50-99 and 100 or more Bq/m3, were 1.13 (95% confidence interval; 0.29-4.40), 1.23 (0.16-9.39) and 0.25 (0.03-2.33), respectively. None of the estimates showed statistical significance, due to small sample size. When the subjects were limited to only include residents of more than 30 years, the estimates did not change substantially. This study did not find that the risk pattern of lung cancer, possibly associated with residential radon exposure, in Misasa Town differed from patterns observed in other countries.
The importance of genetic factors in the etiology of esophageal cancer is uncertain. We addressed the question of heredity in a population-based, nationwide case-control study conducted in Sweden during 1995 through 1997. The study involved 189 patients with esophageal adenocarcinoma, 262 with cardia adenocarcinoma, 167 with esophageal squamous cell carcinoma, and, for comparison, 820 control subjects. Familial occurrence of cancer was explored at face-to-face interviews. Logistic regression, with multivariate adjustment for potential confounders, was used to calculate odds ratios (ORs), which estimated relative risk. Occurrence of esophageal cancer among first-degree relatives did not increase the risk of adenocarcinoma or squamous cell carcinoma of the esophagus. Neither were there any significant associations with familial occurrence of gastric cancer or other gastrointestinal tumors. The risk of cardia adenocarcinoma was moderately increased among persons with first-degree relatives with gastric cancer (OR, 1.6; 95% confidence interval, 1.0-2.6). Familial occurrence of any cancer was not associated with increased risks of any of the three studied tumors. In conclusion, heredity does not seem to contribute importantly to the occurrence of esophageal cancer of any histological type. A weak association between familial gastric cancer and the risk of cardia cancer may represent a genetic link.
UNLABELLED: Variable success rates for identifying axillary (AX) sentinel nodes in breast cancer patients using preoperative lymphoscintigraphy have been reported. We evaluated the effects of age, weight, breast size, method of biopsy, interval after biopsy, and imaging view on the success of sentinel node identification and on the kinetics of radiopharmaceutical migration. METHODS: Preoperative breast lymphoscintigraphy was performed in consecutive breast cancer patients from February 1998 to December 1998. The ipsilateral shoulder was elevated on a foam wedge and the arm was abducted and elevated overhead. Imaging using this modified oblique view of the axilla (MOVA) started immediately after peritumoral injection of Millipore-filtered 99mTc-sulfur colloid and continued until AX sentinel nodes were identified. Anterior views were obtained after MOVA. AX, internal mammary (IM), and clavicular (CL) basins were monitored in all patients. MOVA was compared with the anterior view for sentinel node identification. Age, weight, breast size, method of biopsy, interval after biopsy, and primary tumor location were evaluated for their effects on sentinel node localization and transit times from injection to arrival at the sentinel nodes. RESULTS: Seventy-six lymphoscintigrams were obtained for 75 patients. AX sentinel nodes were revealed in 75 (99%) cases. IM or CL sentinel nodes were found in 19 (25%) cases and were not related to tumor location; exclusive IM drainage was present in 1 (1%) case. Identification of AX sentinel nodes was equivalent with MOVA and anterior views in 18 (24%) patients, was better with MOVA in 20 (26%) patients, and was accomplished only with MOVA in 38 (50%) patients. Median transit time was 17.5 min (range, 1 min to 18 h) after injection, and larger breast size was associated with increased transit time. No effect of age, weight, biopsy method, interval from biopsy, or tumor location on transit time was found. CONCLUSION: Use of MOVA can improve identification of AX sentinel nodes. Although AX drainage is the predominant pattern, a tumor in any portion of the breast can drain to IM sentinel nodes. Transit time was influenced by breast size. Overall short arrival times with this technique allow sentinel lymph node dissection to be performed on the same day as lymphoscintigraphy.
OBJECTIVE: To analyse hereditary familial type II diabetes mellitus (type II DM), including its pattern and the transmitted expression on different sex of type II DM. METHODS: Familial analysis, segregation analysis, tests were used for multifactorial inheritance and threshold analysis. One hundred seventy-seven pedigrees of familial type II DM were studied. RESULTS: The heritability of familial type II DM was 143.06% +/- 3.3%. One dominant major gene might influence the genesis of type II DM. There were 214 nuclear families in 3 different mating types: U x U, U x A and A x A. The segregation ratios of U x U, U x A and A x A were 0.4703, 0.4838 and 0.6712 respectively. The results of tests for multifactorial inheritance and segregation analysis indicated that the genetic pattern of U x A and A x A nuclear families was not multifactorial inheritant and autosomal recessive (AR) but autosomal dominant (AD) inheritance. The genetic pattern of U x U nuclear families was neither AD nor AR inheritance. CONCLUSION: There was genetic heterogeneity in type II DM discovered with subgroupes of autosomal dominant inheritance in type II DM.
OBJECTIVE: To study the mechanism of haze formation and investigate the expression changes of transforming growth factor-alpha (TGF-alpha), transforming growth factor-beta 1(TGF-beta 1) and basic fibroblast growth factor (bFGF) mRNA in corneal epithelium and stroma after photorefractive keratectomy (PRK). METHODS: Sixteen white rabbits were randomly divided into 4 groups, and PRK was performed on each eye of 12 rabbits. The haze formation was examined under a slit-lamp microscope at the 1st, 2nd and 3rd month after PRK, and the expressions of TGF-alpha, TGF-beta 1 and bFGF mRNA were detected with in situ hybridization. RESULTS: The corneal haze formed at the 1st month after PRK. The most prominent haze formation was observed at the 2nd month, and declined gradually at the 3rd month after ablation. TGF-alpha mRNA expression was presented on the normal corneal epithelium and not on the corneal stroma. TGF-beta 1 and bGFG mRNA were expressed by both corneal epithelium and stroma. The capacities for cornea tissue expression of three growth factors mRNA increased after PRK, and the peaks appeared on the 1st, 2nd month. The extent for expressions of three growth factors related proportionally to the haze formation. CONCLUSION: Three growth factors took part in promoting corneal wound healing after PRK, and might contribute to corneal haze formation and development.
OBJECTIVE: To observed the effect of amniotic membrane transplantation (AMT) on expressions of transforming growth factor-beta 1(TGF-beta 1), collagens I, III and fibronectin (FN) in rabbit corneal healing after photorefractive keratectomy (PRK), and investigate the anti-scarring formation mechanism of AMT. METHODS: Ten rabbits underwent bilateral PRK to correct 8 diopters of myopia. One eye was randomly transplanted with preserved human amniotic membrane, and the other eye served as the control. The expressions of TGF-beta 1, collagens I, III and FN were studied by immunohistochemistry at 4 weeks after operation. RESULTS: The expression of TGF-beta 1 in corneal epithelium and keratocytes and collegans in anterior stroma was significantly less in AMT group than in the control group. The expressions of collagens III and FN in anterior stroma of ablation area were also significantly less in AMT group than in the control group. The staining of collagen I had no significant difference between the AMT group and the control group. CONCLUSION: The expressions of TGF-beta 1, collagens III and FN can be suppressed by amniotic membrane after PRK. These data suggest that part of the anti-scarring effect of AMT may be mediated through the suppression of TGF-beta 1, collagens III and FN expression.
OBJECTIVE: To study the feasibility and the morphological mechanism of combined use of steroid hormone (methyltestosterone and ethinyl estradiol) and low dose gossypol for antifertility in adult Wistar rats. METHODS: We used methyltestosterone 20 mg/(kg.d), ethinyl estradiol 100 micrograms/(kg.d), and gossypol 12 mg/(kg.d) to feed male rats for 6 weeks via gastric intubation to induce infertility, then used gossypol 12 mg/(kg.d) alone for another 12 weeks to maintain infertility. Testicular sperm counts, cauda epididymal sperm motility, and sperm silver staining were used to determine infertility and morphology of sperm at the end of the two phases. Testicular morphology of the rats was observed from HE and PAS staining of paraffin sections. F1 generation of the rats would be examined in a series of behavioral tests after their 6-week recovery periods. RESULTS: There was no substantial change in testicular sperm counts of drugs-treated rats both for 6 weeks and 6 plus 12 weeks compared with that of control. But cauda epididymal sperm motility of drugs-treated rats went down to zero at the end of two phrases. The result of sperm silver staining showed that epididymal sperm were all deleterious of either segregation of sperm nucha from sperm head, or separation in annular granule of sperm tail. The observation of testicular morphology suggested that spermatogenesis is only partially affected. The ratios of stages II-III (9.3 +/- 3.4)% and stages IX-X (3.6 +/- 0.6)% were remarkably dropped, but that of stages IV-VI (36.7 +/- 5.0)% obviously ascended comparing with (26.8 +/- 1.7)%, (6.0 +/- 0.4)%, (24.5 +/- 2.7)% of control at the end of 6 plus 12 weeks. Moreover, no adverse effect was found in viscera tissue sections. CONCLUSIONS: Steroid hormone made the procedure of spermatogenesis slower and low dose gossypol caused all sperm lose their activity in epididymis. Both affect the process of spermatogenesis from different endpoints and successfully induce infertility in short term. Low dose gossypol not only executes its antifertility function in epididymis, but also affects the quality of spermatozoal production in testis by impacting the procedures of both acrosomal formation and spermatozoal elongation, so it can completely maintain infertility in long term. The infertility was reversible that the infertile rats can be recovery in about 6 weeks. Their F1 generation were proved to be normal through a set of behavioral tests.
OBJECTIVE: The male contraceptive mechanism in rats of triptonide, isolated from Multiglycosides of Tripterygium wilfordii (GTW), was investigated. METHODS: The dosage of triptonide was 200 micrograms/(kg.d), fed for 8 weeks via gastric intubation. Sperm counts, sperm motility, and sperm silver staining were used to test the antispermatogenic effect of triptonide; the study of morphology was learned from paraffin sections of testis and visceras of triptonide-treated rats; protamine was abstracted from testis by electrophoresis; using antisense mRNA of cyclin D1 and Cdk4 as prodes, we examined the expression of cyclin D1 and Cdk4 through hybridization in situ. RESULTS: Sperm counts (26.43 +/- 3.90) x 10(6)/g and sperm motility(66.0 +/- 6.8)% of triptonide-treated rats were substantially different from those of control, (41.15 +/- 5.51) x 10(6)/g (P < 0.01) and (88.0 +/- 2.0)% (P < 0.001). Paraffin sections of testis of triptonide-treated rats stained by PAS showed that the number of spermatids per 100 sertoli cells (9.15 +/- 0.33) was remarkably decreased compared with control's (10.73 +/- 0.38) (P < 0.001). At the same time, delaying sperm-released process was observed, which affects the nature course of sperm. And the extended vacuoles of vary sizes, the segregation of cells in lumens were also found in the cross-section of testis of rats treated with triptonide. In addition, the contents of protamine (4.6 +/- 2.2)% was extremely decreased, compared with the control's (40.6 +/- 7.2)% (P < 0.001). By using antisense mRNA of cyclin D1 and Cdk4 as prodes, we detected that the expression of the genes was notably increased in spermatids. CONCLUSIONS: The results suggest the antispermatogenic effect of triptonide is very well and it mainly plays its role on spermatids by increasing the expression of cyclin D1 and Cdk4, meanwhile, decreasing the biosynthesis of protamine. The appropriate target region of triptonide makes itself most potency to be a suitable male antifertility drug.
Few studies have provided information on the role of smoking and alcohol in the carcinogenesis of gastric cancer by sub-site and histologic type. The relationship of snuff dipping with risk of gastric cancer has also been rarely studied. In a population-based case-control study conducted in 5 counties of Sweden from February 1989 to January 1995, a total of 90 cases of gastric cardia cancer, 260 and 164 cases of distal gastric cancer of intestinal and diffuse types, respectively, and 1164 frequency-matched control subjects were personally interviewed about life-time smoking, use of smokeless tobacco and use of alcohol 20 years ago. Current smokers had a higher risk than never-smokers for all 3 kinds of gastric adenocarcinoma [odds ratio (OR) 1.7, 95% confidence interval (CI) 1.0-3.1 for gastric cardia adenocarcinoma; OR 1.8, 95% CI 1.2-2.7 for distal gastric cancer of intestinal type; and OR 2.2, 95% CI 1.4-3.5 for distal gastric cancer of diffuse type], and the risk rose with increasing dose and duration of smoking among current smokers. However, no elevated risk was observed for ex-smokers. Neither intake of alcoholic beverages nor snuff dipping was associated with an increased risk of any type of cardia or gastric cancer. Our study did not support the hypothesis that the role of tobacco differs by sub-site and histologic sub-type of gastric cancer.
The proinflammatory cytokine interleukin-1 beta (IL-1beta) is thought to play an important role in the stimulation of the inflammatory response following ischemia and reperfusion. This study investigated the inflammatory effect of IL-1beta during transient focal cerebral ischemia and reperfusion in the mouse transduced with the interleukin-1 receptor antagonist (IL-1ra) gene. An adenoviral vector encoding, either the human IL-1ra gene (AdRSVIL-1ra) or the LacZ gene (AdRSVlacZ) or normal saline, were injected into the right lateral ventricles of adult CD-1 mice (n=96). Five days later, the mice received 1 h temporary middle cerebral artery occlusion (tMACAO) followed by 23 h reperfusion. Cerebral blood flow (CBF), infarct volume, blood-brain barrier (BBB) permeability, and the number of intracellular adhesion molecule-1 positive vessels were measured to determine the effect of IL-1beta during postischemic reperfusion. Infarct volume in the AdRSVIL-1ra-transduced mice was markedly reduced compared to the AdRSVlacZ-transduced and saline-injected mice (36.0+/-5.3 mm(3) vs. 60.0+/-6.2 mm(3), 69. 5+/-6.3 mm(3), after 23 h of reperfusion, n=6-8 per group, p<0.05). BBB disruption and intracellular adhesion molecule-1 expression (135+/-23 vs. 311+/-40 and 357+/-51, n=6-8 per group, p<0.05) in the AdRSVIL-1ra-transduced mice were also less than that of the AdRSVlacZ-transduced and saline-injected mice. Our studies demonstrated that overexpression of IL-1ra in the mouse brain can downregulate intracellular adhesion molecule-1 expression both in the cortex and basal ganglia, which suggests that IL-1beta may play an important role in the activation of the inflammatory response during focal cerebral ischemia by promoting leukocyte adhesion to endothelial cells. The decrease of BBB disruption in AdRSVIL-1ra-transduced mice suggests that the endothelial cells may be a target for IL-1beta during postischemic reperfusion.
Five new oleanane-type glycosides (1-5), along with two known triterpene saponins, were isolated from the roots of Pulsatilla patens var. multifida (Ranunculaceae). The structures of the new triterpene saponins were elucidated as 3-O-beta-D-glucopyranosyl(1-->2)-beta-D-galactopyranosyl hederagenin 28-O-beta-D-glucopyranosyl ester (1), hederagenin 3-O-[beta-D-glucopyranosyl(1-->2)][beta-D-glucopyranosyl(1-->6)]-beta -D-galactopyranoside (2), 3-O-beta-D-glucopyranosyl bayogenin 28-O-alpha-L-rhamnopyranosyl(1-->4)-beta-D-glucopyranosyl(1-->6)-beta -D-glucopyranosyl ester (3), 3-O-beta-D-glucopyranosyl(1-->2)-beta-D-galactopyranosyl oleanolic acid 28-O-alpha-L-rhamnopyranosyl(1-->4)-beta-D-glucopyranosyl(1-->6)-beta -D-glucopyranosyl ester (4), and 3-O-[beta-D-glucopyranosyl(1-->2)][beta-D-glucopyranosyl(1-->6)]-beta -D-galactopyranosyl hederagenin 28-O-alpha-L-rhamnopyranosyl(1-->4)-beta-D-glucopyranosyl(1-->6)-beta -D-glucopyranosyl ester (5). Structure elucidation was accomplished by 1D and 2D NMR (HMQC, HMBC, and ROESY) methods, FABMS, and hydrolysis.
A physical map of the mouse genome is an essential tool for both positional cloning and genomic sequencing in this key model system for biomedical research. Indeed, the construction of a mouse physical map with markers spaced at an average interval of 300 kb is one of the stated goals of the Human Genome Project. Here we report the results of a project at the Whitehead Institute/MIT Center for Genome Research to construct such a physical map of the mouse. We built the map by screening sequenced-tagged sites (STSs) against a large-insert yeast artificial chromosome (YAC) library and then integrating the STS-content information with a dense genetic map. The integrated map shows the location of 9,787 loci, providing landmarks with an average spacing of approximately 300 kb and affording YAC coverage of approximately 92% of the mouse genome. We also report the results of a project at the MRC UK Mouse Genome Centre targeted at chromosome X. The project produced a YAC-based map containing 619 loci (with 121 loci in common with the Whitehead map and 498 additional loci), providing especially dense coverage of this sex chromosome. The YAC-based physical map directly facilitates positional cloning of mouse mutations by providing ready access to most of the genome. More generally, use of this map in addition to a newly constructed radiation hybrid (RH) map provides a comprehensive framework for mouse genomic studies.
The role of the adenosine A3 receptor continues to baffle, and, despite an increasing number of studies, the currently available data add to, rather than alleviate, the existing confusion. The reported effects of adenosine A3 receptor stimulation appear to depend on the pattern of drug administration (acute vs. chronic), dose, and type of the target tissue. Thus, while acute exposure to A3 receptor agonists protects against myocardial ischemia, it is severely damaging when these agents are given shortly prior to cerebral ischemia. Mast cells degranulate when their A3 receptors are stimulated. Degranulation of neutrophils is, on the other hand, impaired. While reduced production of reactive nitrogen species has been reported following activation of A3 receptors in collagen-induced arthritis, the process appears to be enhanced in cerebral ischemia. Indeed, immunocytochemical studies indicate that both pre- and postischemic treatment with A3 receptor antagonist dramatically reduces nitric oxide synthase in the affected hippocampus. Even more surprisingly, low doses of A3 receptor agonists seem to enhance astrocyte proliferation, while high doses induce their apoptosis. This review concentrates on the studies of cerebral A3 receptors and, based on the available evidence, discusses the possibility of adenosine A3 receptor serving as an integral element of the endogenous cerebral neuroprotective complex consisting of adenosine and its receptors.
Drosophila Suppressor of fused (Su(fu)) encodes a novel 468-amino-acid cytoplasmic protein which, by genetic analysis, functions as a negative regulator of the Hedgehog segment polarity pathway. Here we describe the primary structure, tissue distribution, biochemical and functional analyses of a human Su(fu) (hSu(fu)). Two alternatively spliced isoforms of hSu(fu) were identified, predicting proteins of 433 and 484 amino acids, with a calculated molecular mass of 48 and 54 kDa, respectively. The two proteins differ only by the inclusion or exclusion of a 52-amino-acid extension at the carboxy terminus. Both isoforms were expressed in multiple embryonic and adult tissues, and exhibited a developmental profile consistent with a role in Hedgehog signaling. The hSu(fu) contains a high-scoring PEST-domain, and exhibits an overall 37% sequence identity (63% similarity) with the Drosophila protein and 97% sequence identity with the mouse Su(fu). The hSu(fu) locus mapped to chromosome 10q24-q25, a region which is deleted in glioblastomas, prostate cancer, malignant melanoma and endometrial cancer. HSu(fu) was found to repress activity of the zinc-finger transcription factor Gli, which mediates Hedgehog signaling in vertebrates, and to physically interact with Gli, Gli2 and Gli3 as well as with Slimb, an F-box containing protein which, in the fly, suppresses the Hedgehog response, in part by stimulating the degradation of the fly Gli homologue. Coexpression of Slimb with Su(fu) potentiated the Su(fu)-mediated repression of Gli. Taken together, our data provide biochemical and functional evidence for the hypothesis that Su(fu) is a key negative regulator in the vertebrate Hedgehog signaling pathway. The data further suggest that Su(fu) can act by binding to Gli and inhibiting Gli-mediated transactivation as well as by serving as an adaptor protein, which links Gli to the Slimb-dependent proteasomal degradation pathway.
The determination of the structural and functional contributions of natural modified nucleosides to tRNA has been limited by lack of an approach that can systematically incorporate the modified units. We have produced a number of oligonucleotide analogs, of the anticodon of yeast tRNA(Phe) by, combining standard automated synthesis for the major nucleosides with specialty chemistries for the modified nucleosides. In this study, both naturally occurring and unnatural modified nucleotides were placed in native contexts. Each oligonucleotide was purified and the nucleoside composition determined to validate the chemistry. The RNAs were denatured and analyzed to determine the van't Hoff thermodynamic parameters. Here, we report the individual thermodynamic contributions for Cm, Gm, m1G, m5C, psi. In addition m5m6U, m1psi, and m3psi, were introduced to gain additional understanding of the physicochemical contribution of psi and m5C at an atomic level. These oligonucleotides demonstrate that modifications have measurable thermodynamic contributions and that loop modifications have global contributions.