EXAFS studies of (Pb,Cd)1212 phase superconductor and (Bi,Cd)1212 phase compound.
Explore the source record for details and available documents.
Journal Article↗
Biomedical subjects
T Liu
Publications and source records attributed to T Liu.
Macrophage control of herpes simplex virus type 1 replication in the peripheral nervous system.
After corneal infection, herpes simplex virus type 1 (HSV-1) invades sensory neurons with cell bodies in the trigeminal ganglion (TG), replicates briefly, and then establishes a latent infection in these neurons. HSV-1 replication in the TG can be detected as early as 2 days after corneal infection, reaches peak titers by 3-5 days after infection, and is undetectable by 7-10 days. During the period of HSV-1 replication, macrophages and gammadelta TCR+ T lymphocytes infiltrate the TG, and TNF-alpha, IFN-gamma, the inducible nitric oxide synthase (iNOS) enzyme, and IL-12 are expressed. TNF-alpha, IFN-gamma, and the iNOS product nitric oxide (NO) all inhibit HSV-1 replication in vitro. Macrophage and gammadelta TCR+ T cell depletion studies demonstrated that macrophages are the main source of TNF-alpha and iNOS, whereas gammadelta TCR+ T cells produce IFN-gamma. Macrophage depletion, aminoguanidine inhibition of iNOS, and neutralization of TNF-alpha or IFN-gamma all individually and synergistically increased HSV-1 titers in the TG after HSV-1 corneal infection. Moreover, individually depleting macrophages or neutralizing TNF-alpha or IFN-gamma markedly reduced the accumulation of both macrophages and gammadelta TCR+ T cells in the TG. Our findings establish that after primary HSV-1 infection, the bulk of virus replication in the sensory ganglia is controlled by macrophages and gammadelta TCR+ T lymphocytes through their production of antiviral molecules TNF-alpha, NO, and IFN-gamma. Our findings also strongly suggest that cross-regulation between these two cell types is necessary for their accumulation and function in the infected TG.
Animals↗
Effect of systemic cyclosporine on tumor recurrence after liver transplantation in a model of hepatocellular carcinoma.
BACKGROUND: Long-term results after liver transplantation for hepatocellular carcinoma have been disappointing, largely because of the high recurrence rate. It is controversial whether the immunosuppressed state of the recipient contributes to this recurrence rate. We have developed a model in the rat system to examine the effect of immunosuppression on tumor recurrence after transplantation, as well as to evaluate other treatment strategies to decrease the recurrence rate. METHODS: A 2-mm3 nodule of Morris hepatoma 3924a was implanted intrahepatically at day 0. At postimplant day 16, the animals underwent syngeneic orthotopic liver transplantation. Two treatment groups were established. Group I received saline injections subcutaneously for 2 weeks, while group II received subcutaneous cyclosporine injections at 3 mg/kg/day for 14 days. Animal survival, tumor recurrence rate, and sites of recurrence and number of pulmonary nodules were recorded. RESULTS: Overall survival rate was reduced in animals receiving cyclosporine. The mean survival time was 74.4 days (SEM 6.39 days) in saline-treated animals and 50.4 days (SEM 7.63 days) in the cyclosporine-treated animals. The proportion surviving in group 1 was 47% and in group 2 was 18%. This difference in survival was statistically significant (P=0.025). The incidence of pulmonary nodules was increased in the cyclosporine-treated animals, and tumor recurrence in extrapulmonary sites was seen only in the cyclosporine-treated animals. CONCLUSION: Results from this study suggest that cyclosporine has an adverse effect on tumor recurrence after transplantation. This model will be useful to further examine treatment strategies to improve the outcome of transplantation for hepatocellular carcinoma.
Animals↗
Zinc alleviates thermal hyperalgesia due to partial nerve injury.
Zinc has recently been shown to alleviate inflammatory hyperalgesia. In the present study, we showed that intrathecal, intraplantar or systemic injection of zinc chloride significantly relieved thermal hyperalgesia in rats with sciatic nerve injury. Alleviation of thermal hyperalgesia was dose dependent in each case, although higher doses were required for i.p. injections (ED50 = 13.6 nmol) than for intrathecal (ED50 = 0.05 nmol) or intraplantar injections (ED = 0.3 nmol). Neither intrathecal nor intraplantar zinc chloride influenced thermal nociception in normal rats without nerve injury. The results provide the first evidence that zinc alleviates neuropathic hyperalgesia.
Animals↗
Nested case-control study of esophageal cancer in relation to occupational exposure to silica and other dusts.
BACKGROUND: Standardized proportionate mortality ratio (SPMR) was found to be 2.2 (95% CI = 1.3-3.5) for esophageal cancer (EC) among workers exposed to refractory brick dust in a large iron-steel complex in China. METHODS: A nested case-control design within a cohort of industrial workers. One hundred and twenty-five EC cases and 250 controls were identified from the death registry file. Interviews were conducted of the next of kin for past exposure information on job, domestic, and lifestyle factors. History of occupational exposure to various dusts was reconstructed from personnel files and by interviewing colleagues utilizing a job-exposure matrix. RESULTS: After adjusting for confounders, occupational exposure to silica dust was the most important risk factor among all variables investigated, with a 2.8-fold risk and a clear dose-response by length of exposure. Alcohol drinking (OR = 1.8) and coal cooking (OR = 2.0) were risk factors and high consumption of fruit diet (OR = 0.5) and meat diet (OR = 0.6) were protective factors. CONCLUSIONS: The relationship between occupational exposure to silica dust and the risk of EC found in an earlier SPMR study was confirmed. Ingestion of silica particles after lung clearance may increase the risk of EC among workers exposed to silica.
Aged↗
Intragraft CD45 RO gene expression is an early marker to detect small bowel allograft rejection in rats.
Wistar Furth (WF) intestinal allografts were transplanted into Sprague-Dawley (SD) rats. Recipients were randomly allocated into the following groups: (1) no treatment; (2) cyclosporine (CsA) 6 mg/kg/day, daily, subcutaneously (s.c.; full-dose therapy); (3) CsA 3 mg/kg/day, daily, s.c. (half-dose therapy); and (4) CsA 3 mg/kg/day, daily, s.c. + Tripterygium Wilfordii Hook. WF (TW) 3 mg/kg/day, daily, s.c. WF rats with intestinal autografts were used as controls. CD45RO intragraft expression and its index (CD45RO/CD45), measured by reverse transcription polymerase chain reaction (RT-PCR), were significantly elevated in untreated and half-dose CsA-treated allografts as early as postoperative day (POD) 4, when rejection of intestinal allografts was not detected by routine pathology. Intestinal permeability measured by Tc-DTPA radioassay was significantly elevated in untreated allografts on POD 6. Histology showed that there was severe rejection in untreated intestinal allografts and mild rejection in allografts treated with a half dose of CsA on POD 6. There was a normal CD45RO expression, permeability, and histology in intestinal allografts treated with either a full dose of CsA or a half dose of CsA + TW. These data indicate that CD45RO intragraft gene expression is an early marker to detect intestinal allograft rejection in rats.
Animals↗
Acetylcholine receptor alpha subunit mRNA expression in human thymus: augmented expression in myasthenia gravis and upregulation by interferon-gamma.
Previous studies by us and others have demonstrated the expression of acetylcholine receptors on epithelial cells in the thymus of myasthenia gravis (MG) and control subjects. In the present experiments, we used a reverse transcription-polymerase chain reaction (RT-PCR) to analyze the profile of the two major isoforms of the alpha chain of these receptors (AChRalpha), P3A- and P3A+, in thymus tissue obtained from MG and control subjects and a human thymic epithelial cell line (TEC9). In addition, using a semiquantitative RT-PCR, we compared the amounts of P3A- and P3A+ mRNA expressed in thymic tissue obtained from these two sources and determined if their expression in TEC9 is modulated by cytokines. We found that mRNAs encoding P3A- and P3A+ are expressed at approximately a 5:1 ratio in both MG and control thymus tissue. This contrasts with skeletal muscle where mRNAs encoding these isoforms are expressed equally. A pattern of preferential P3A- vs P3A+ mRNA expression was also observed in TEC9. We observed 2.8-fold greater expression of both isoforms in MG than in control thymus. Expression of both isoforms in TEC9 was enhanced significantly by treatment with interferon-gamma whereas IL-1alpha, IL-4, and IL-6 had no effect. Thus, there is differential regulation of AChRalpha variants in thymus and TEC relative to muscle and interferon-gamma represents a novel regulator of AChRalpha mRNA expression. MG thymus is distinguished by increased expression of both isoforms of this autoantigen, a finding that may reflect enhancement of transcription by local microenvironmental factors.
Adolescent↗
Altered ligand binding of D1 and D2 dopamine receptors in response to hypoxia and posthypoxic reoxygenation.
Explore the source record for details and available documents.
Animals↗
Treatment of postmenopausal women with osteoporosis or low bone density with raloxifene. Raloxifene Study Group.
Raloxifene, a selective estrogen receptor modulator (SERM), has been shown to improved bone mineral density (BMD) and serum lipid profiles in healthy postmenopausal women. The objective of this study was to examine the effects of raloxifene on BMD, biochemical markers of bone metabolism and serum lipids in postmenopausal women with low bone density or osteoporosis. This Phase II, multicenter, 24-month, double-masked study assessed the efficacy and safety of raloxifene in 129 postmenopausal women (mean age +/- SD: 60.2 +/- 6.7 years) with osteoporosis or low bone density (baseline mean lumbar spine BMD T-score: -2.8). Women were randomly assigned to one of three treatment groups: placebo, 60 mg/day raloxifene-HCl (RLX 60) or 150 mg/day raloxifene-HCL (RLX 150) and concomitantly received 1000 mg/day calcium and 300 U/day vitamin D3. At 24 months, BMD was significantly increased in the lumbar spine (+3.2%), femoral neck (+2.1%), trochanter (+2.7%) and total hip (+1.6%) in the RLX 60 group compared with the placebo group (p < 0.05). The RLX 150 group had increases in BMD similar to those observed with RLX 60. A greater percentage of raloxifene-treated patients, compared with those receiving placebo, had increased BMD (p < 0.05). Serum bone-specific alkaline phosphatase activity, serum osteocalcin, and urinary type I collagen:creatinine ratio were significantly decreased in the RLX-treated groups, compared with the placebo group (p < 0.01). RLX 60 treatment significantly decreased serum levels of triglycerides, and total- and LDL-cholesterol levels (p < 0.01). The rates of patient discontinuation and adverse events were not significantly different among groups. In this study, raloxifene increased bone density, decreased bone turnover, and improved the serum lipid profile with minimal adverse events, and may be a safe and effective treatment for postmenopausal women with osteoporosis or low bone density.
Aged↗
Missense mutations in hMLH1 associated with colorectal cancer.
One of the most prevalent hereditary syndromes associated with colorectal cancer is hereditary nonpolyposis colorectal cancer (HNPCC). The inherited gene defects in HNPCC have been shown to reside in DNA mismatch repair genes, mostly hMSH2 or hMLH1. Most HNPCC patients are heterozygous with regard to the relevant mismatch repair gene; they have one normal and one mutated allele, and mismatch repair in normal somatic cells is functional. Cancer predisposition in HNPCC is believed to be associated with the loss of the wild-type allele in somatic cells, resulting in defective DNA mismatch repair. This gives rise to DNA microsatellite instability (MSI), an increased somatic mutation rate, and eventually, to the accumulation of mutations in genes involved in colorectal carcinogenesis. In support of this theory, colorectal tumors in HNPCC patients and in mice deficient for hMSH2 or hMLH1 show MSI. Here, we describe two missense mutations in hMLH1 exon 16 associated with colorectal cancer. Interestingly, the tumors do not show MSI. This raises some potentially important issues. First, even microsatellite-negative colorectal tumors can be associated with germline mutations and these will be missed if an MSI test is used to select patients for mutation screening. Second, the lack of MSI in these cases suggests that the mechanism involved in carcinogenesis could be different from that generally hypothesized.
Adaptor Proteins, Signal Transducing↗
Late course accelerated fractionation in radiotherapy of esophageal carcinoma.
PURPOSE: To evaluate the efficacy of adding accelerated fractionation after completing two thirds of routine fractionated radiotherapy in esophageal carcinoma. METHODS AND MATERIALS: From April 1988 to April 1990, 85 patients with histologically confirmed carcinoma of the esophagus were randomized into two groups. (1) The conventional fractionation (CF) group, received 1.8 Gy per day five times a week to a total dose of 68.4 Gy in 7-8 weeks, and (2) the late course accelerated hyperfractionated (LCAF) group which received the same schedule as the CF group during the first two thirds of the course of radiotherapy to a dose of 41.4 Gy/23 fx/4 to 5 weeks. This was then followed by accelerated hyperfractionation using reduced fields. In the LCAF portion of the radiotherapeutic course, the irradiation schedule was changed to 1.5 Gy twice a day, with an interval of 4 h between fractions, to a dose of 27 Gy/18 fx. Thus the total dose was also 68.4 Gy, the same as the CF group, but the course of radiotherapy was shorter, being only 6.4 weeks. The same Cobalt 60 teletherapy unit was used to treat all the cases. RESULTS: The 5 year actuarial survival and disease-free survival rates in the LCAF group were 34% and 42%, as compared to 15% and 15% respectively in the CF group, all statistically significant. Better local control was seen in the LCAF group than in the CF group, the 5 year control rates being 55% versus 21% (P = 0.003). The acute reactions were increased but acceptable in the LCAF patients, the radiation treatments could be completed without any breaks. The late reactions as observed after 5 years were not increased in comparison with the CF patients. CONCLUSIONS: The results from this study show that the late course accelerated hyperfractionated radiotherapy regime can improve results in esophageal carcinoma, with acceptable acute reactions as compared to conventional radiotherapy.
Esophageal Neoplasms↗
Cincinnati Prehospital Stroke Scale: reproducibility and validity.
STUDY OBJECTIVE: The Cincinnati Prehospital Stroke Scale (CPSS) is a 3-item scale based on a simplification of the National Institutes of Health (NIH) Stroke Scale. When performed by a physician, it has a high sensitivity and specificity in identifying patients with stroke who are candidates for thrombolysis. The objective of this study was to validate and verify the reproducibility of the CPSS when used by prehospital providers. METHODS: The CPSS was performed and scored by a physician certified in the use of the NIH Stroke Scale (gold standard). Simultaneously, a group of 4 paramedics and EMTs scored the same patient. RESULTS: A total of 860 scales were completed on a convenience sample of 171 patients from the emergency department and neurology inpatient service. Of these patients, 49 had a diagnosis of stroke or transient ischemic attack. High reproducibility was observed among prehospital providers for total score (intraclass correlation coefficient [rI],.89; 95% confidence interval [CI],.87 to.92) and for each scale item: arm weakness, speech, and facial droop (.91,.84, and.75, respectively). There was excellent intraclass correlation between the physician and the prehospital providers for total score (rI,.92; 95% CI,.89 to.93) and for the specific items of the scale (.91,.87, and.78, respectively). Observation by the physician of an abnormality in any 1 of the 3 stroke scale items had a sensitivity of 66% and specificity of 87% in identifying a stroke patient. The sensitivity was 88% for identification of patients with anterior circulation strokes. CONCLUSION: The CPSS has excellent reproducibility among prehospital personnel and physicians. It has good validity in identifying patients with stroke who are candidates for thrombolytic therapy, especially those with anterior circulation stroke.
Aged↗
Acute stroke: delays to presentation and emergency department evaluation.
STUDY OBJECTIVE: To document prehospital and inhospital time intervals from stroke onset to emergency department evaluation and to identify factors associated with presentation to the ED within 3 hours of symptom onset, the current time window for thrombolytic therapy. METHODS: Patients admitted through the ED with a diagnosis of stroke were identified through admitting logs. Time intervals were obtained from EMS runsheets and ED records. Information regarding first medical contact, education, and income was obtained by patient interview. Baseline variables were analyzed to assess association with ED arrival within 3 hours of symptom onset; variables significant on univariate analysis were placed in a multivariable model. RESULTS: There were 151 stroke patients (59% white and 41% black). Time of stroke onset and time to ED arrival were documented for 119 patients (79%). The median time from stroke onset to ED arrival was 5.7 hours; 46 patients (30%) presenting within 3 hours. Of those with times recorded, the median time from stroke onset to EMS arrival was 1.7 hours. Multivariable logistic regression identified use of EMS (odds ratio [OR], 4.0; 95% confidence interval [CI], 1.3 to 12.1) and white race (OR, 3.5; 95% CI, 1.3 to 10) as being independently associated with ED arrival within 3 hours of symptom onset. Median time from ED arrival to physician evaluation was 20 minutes. Median time from ED arrival to computed tomographic evaluation was 72 minutes. When patients were asked the main reason they sought medical attention, 40% (60/141) of those able to be interviewed said that they themselves did not decide to seek medical attention, but rather a friend or family member told them they should go to the hospital. CONCLUSION: The median time from stroke onset to ED evaluation was 5.7 hours, with almost a third of patients presenting within 3 hours. Use of EMS and white race were independently associated with arrival within 3 hours.
Acute Disease↗
Issues in the management of nasopharyngeal carcinoma.
Explore the source record for details and available documents.
Carcinoma, Squamous Cell↗
Microsatellite instability and mismatch repair gene inactivation in sporadic pancreatic and colon tumours.
Genomic instability has been proposed as a new mechanism of carcinogenesis involved in hereditary non-polyposis colorectal cancer (HNPCC) and in a large number of sporadic cancers like pancreatic and colon tumours. Mutations in human mismatch repair genes have been found in HNPCC patients, but their involvement in sporadic cancer has not been clarified yet. In this study we screened 21 pancreatic and 23 colorectal sporadic cancers for microsatellite instability by ten and six different microsatellite markers respectively. Microsatellite alterations were observed at one or more loci in 66.6% (14/21) of pancreatic cancers and in 26% (6/23) colon tumours, but all the pancreatic and half of the colon samples showed a low rate of microsatellite instability. All the unstable samples were further analysed for mutations in the hMLH1 and hMSH2 genes and for hypermethylation of the hMLH1 promoter region. Alterations in the hMLH1 gene were found only in colorectal tumours with a large presence of microsatellite instability. None of the pancreatic tumours showed any alteration in the two genes analysed. Our results demonstrate that microsatellite instability is unlikely to play a role in the tumorigenesis of sporadic pancreatic cancers and confirm the presence of mismatch repair gene alterations only in sporadic colon tumours with a highly unstable phenotype.
Adaptor Proteins, Signal Transducing↗
Various mutation screening techniques in the DNA mismatch repair genes hMSH2 and hMLH1.
Germline alterations in one of five human DNA mismatch repair genes (hMSH2, hMLH1, hPMS1, hPMS2, and hMSH6) cause hereditary nonpolyposis colorectal cancer. Mutation analyses of these genes reveal gene carriers with a high risk for colorectal cancer, who benefit from surveillance to prevent disease. Equally important, presymptomatic testing allows nondisposed individuals to discontinue surveillance. We tested different mutation screening methods to optimize mutation detection in hMSH2 and hMLH1. Affected members from a total of 142 unrelated colorectal cancer families were analyzed. Denaturant gradient gel electrophoresis (DGGE), RT-PCR, and the protein truncation test (PTT) were used to screen for mutations on a DNA or RNA basis, respectively. In addition, a mutation-specific test on genomic DNA was used to find the Finnish mutation no. 1, a deletion of hMLH1 exon 16. DGGE identified most of the mutations in the mismatch repair genes hMLH1 and hMSH2. The RNA-based techniques were used to identify large deletions; however, these were rare in our materials. We describe our compiled results and experience from all our mutation screening studies, as well as unpublished data from our last DGGE screening of 58 patients and RT-PCR and PTT screening of 73 patients.
Adaptor Proteins, Signal Transducing↗
Major concerns and needs of breast cancer patients.
Between 1989 and 1991, 102 breast cancer patients completed a questionnaire survey on concerns and needs at their first visit to the University Clinic after they were diagnosed or treated for breast cancer at other clinics. Their major concerns and needs were health, family, finances, work, the future, self-esteem, counseling and support for themselves and their family. Married women and those younger than 50 years were more likely to have concerns about their family. Nonwhites had more concerns about finances and work than white women, with an odds ratio (OR) of 6.58. Older women and those married, however, had less concerns about finances and work than younger women and those not married, with ORs of 0.96 and 0.34, respectively. Fewer nonwhite than white patients expressed concerns about their future (OR = 0.31). Young women were more concerned about self-esteem than older women. More nonwhites than whites and more married than unmarried women expressed needs for family counseling and support (OR = 3.58 and 3.68, respectively). Help for interpreting information was required more frequently by nonwhites than whites (OR = 7.25, 95% confidence interval [CI] = 2.19-24.00). Nonwhite women also tended to require more referrals than whites. In summary, major concerns and needs varied among patients of different demographic characteristics, especially those of age, race, and marital status.
Adaptation, Psychological↗
Association with oleic acid vesicles enhances manganese III mesoporphyrin absorption and biliary elimination in rats.
OBJECTIVE: To determine whether the association of manganese III mesoporphyrin (MnMeso), an oral MR contrast agent, to oleic acid (OA) vesicles will improve absorption and delivery of MnMeso to the liver. METHODS: MnMeso or MnMeso-OA vesicle suspension was intraduodenally administered to rats and the time course of MnMeso concentration in plasma, bile, and intestinal solution was determined. Tissue concentrations of MnMeso in the liver were also determined. RESULTS: Association of MnMeso to OA reduced the time it took to reach one-half absorption maximum, TC50, and enhanced the rate and the extent of biliary elimination of this contrast agent. In addition, the results obtained from dose-titration studies indicate that MnMeso-OA vesicle complex may enhance MnMeso accumulation in the liver, observed as a lower dose required to reach equivalent tissue concentration. Taken together, complexion to OA vesicles may provide rapid absorption, enhanced liver accumulation, and efficient elimination of MnMeso. CONCLUSIONS: Association with OA vesicles may enhance the rate of MnMeso absorption and biliary excretion while promoting the extent of liver accumulation of MnMeso in rats. This strategy may provide a means to provide safe and effective use of MnMeso as an MR contrast medium.
Animals↗