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Showing papers by "University of Tennessee Health Science Center published in 1998"


Journal ArticleDOI
18 Mar 1998-JAMA
TL;DR: Reduced sodium intake and weight loss constitute a feasible, effective, and safe nonpharmacologic therapy of hypertension in older persons.
Abstract: Context.—Nonpharmacologic interventions are frequently recommended for treatment of hypertension in the elderly, but there is a paucity of evidence from randomized controlled trials in support of this recommendation.Objective.—To determine whether weight loss or reduced sodium intake is effective in the treatment of older persons with hypertension.Design.—Randomized controlled trial.Participants.—A total of 875 men and women aged 60 to 80 years with systolic blood pressure lower than 145 mm Hg and diastolic blood pressure lower than 85 mm Hg while receiving treatment with a single antihypertensive medication.Setting.—Four academic health centers.Intervention.—The 585 obese participants were randomized to reduced sodium intake, weight loss, both, or usual care, and the 390 nonobese participants were randomized to reduced sodium intake or usual care. Withdrawal of antihypertensive medication was attempted after 3 months of intervention.Main Outcome Measure.—Diagnosis of high blood pressure at 1 or more follow-up visits, or treatment with antihypertensive medication, or a cardiovascular event during follow-up (range, 15-36 months; median, 29 months).Results.—The combined outcome measure was less frequent among those assigned vs not assigned to reduced sodium intake (relative hazard ratio, 0.69; 95% confidence interval [CI], 0.59-0.81; P<.001) and, in obese participants, among those assigned vs not assigned to weight loss (relative hazard ratio, 0.70; 95% CI, 0.57-0.87; P<.001). Relative to usual care, hazard ratios among the obese participants were 0.60 (95% CI, 0.45-0.80; P<.001) for reduced sodium intake alone, 0.64 (95% CI, 0.49-0.85; P=.002) for weight loss alone, and 0.47 (95% CI, 0.35-0.64; P<.001) for reduced sodium intake and weight loss combined. The frequency of cardiovascular events during follow-up was similar in each of the 6 treatment groups.Conclusion.—Reduced sodium intake and weight loss constitute a feasible, effective, and safe nonpharmacologic therapy of hypertension in older persons.

1,115 citations


Journal ArticleDOI
01 May 1998-Cell
TL;DR: Reconstitution experiments demonstrate that Jak2 is not required for the generation of lymphoid progenitors, their amplification, or functional differentiation, and plays a critical, nonredundant role in the function of a specific group of cytokines receptors.

1,110 citations


Journal ArticleDOI
01 Sep 1998-Blood
TL;DR: Polyclonal donor-derived T-cell lines specific for EBV proteins can be used safely to prevent EBV-related immunoblastic lymphoma after allogeneic marrow transplantation and may also be effective in the treatment of established disease.

1,061 citations


Journal ArticleDOI
TL;DR: A structural basis for the hypothesis that pigs may serve as “mixing vessels” for the generation of human-avian influenza A virus reassortants, similar to those responsible for the 1957 and 1968 pandemics is demonstrated.
Abstract: Genetic and biologic observations suggest that pigs may serve as “mixing vessels” for the generation of human-avian influenza A virus reassortants, similar to those responsible for the 1957 and 1968 pandemics. Here we demonstrate a structural basis for this hypothesis. Cell surface receptors for both human and avian influenza viruses were identified in the pig trachea, providing a milieu conducive to viral replication and genetic reassortment. Surprisingly, with continued replication, some avian-like swine viruses acquired the ability to recognize human virus receptors, raising the possibility of their direct transmission to human populations. These findings help to explain the emergence of pandemic influenza viruses and support the need for continued surveillance of swine for viruses carrying avian virus genes.

1,010 citations


Journal ArticleDOI
08 Jul 1998-JAMA
TL;DR: In this study, prolonged administration of methylprednisolone in patients with unresolving ARDS was associated with improvement in lung injury and MODS scores and reduced mortality.
Abstract: Context.—No pharmacological therapeutic protocol has been found effective in modifying the clinical course of acute respiratory distress syndrome (ARDS) and mortality remains greater than 50%.Objective.—To determine the effects of prolonged methylprednisolone therapy on lung function and mortality in patients with unresolving ARDS.Design.—Randomized, double-blind, placebo-controlled trial.Setting.—Medical intensive care units of 4 medical centers.Participants.—Twenty-four patients with severe ARDS who had failed to improve lung injury score (LIS) by the seventh day of respiratory failure.Interventions.—Sixteen patients received methylprednisolone and 8 received placebo. Methylprednisolone dose was initially 2 mg/kg per day and the duration of treatment was 32 days. Four patients whose LIS failed to improve by at least 1 point after 10 days of treatment were blindly crossed over to the alternative treatment.Main Outcome Measures.—Primary outcome measures were improvement in lung function and mortality. Secondary outcome measures were improvement in multiple organ dysfunction syndrome (MODS) and development of nosocomial infections.Results.—Physiological characteristics at the onset of ARDS were similar in both groups. At study entry (day 9 [SD, 3] of ARDS), the 2 groups had similar LIS, ratios of PaO2 to fraction of inspired oxygen (FIO2), and MODS scores. Changes observed by study day 10 for methylprednisolone vs placebo were as follows: reduced LIS (mean [SEM], 1.7 [0.1] vs 3.0 [0.2]; P<.001); improved ratio of PaO2 to FIO2 (mean [SEM], 262 [19] vs 148 [35]; P<.001); decreased MODS score (mean [SEM], 0.7 [0.2] vs 1.8 [0.3]; P<.001); and successful extubation (7 vs 0; P=.05). For the treatment group vs the placebo group, mortality associated with the intensive care unit was 0 (0%) of 16 vs 5 (62%) of 8 (P=.002) and hospital-associated mortality was 2 (12%) of 16 vs 5 (62%) of 8 (P=.03). The rate of infections per day of treatment was similar in both groups, and pneumonia was frequently detected in the absence of fever.Conclusions.—In this study, prolonged administration of methylprednisolone in patients with unresolving ARDS was associated with improvement in lung injury and MODS scores and reduced mortality.

872 citations



Journal ArticleDOI
TL;DR: A double-blind, randomized, placebo-controlled trial in four groups of pregnant women at high risk for preeclampsia, including 471 women with pregestational insulin-treated diabetes mellitus, 774 women with chronic hypertension, 688 women with multifetal gestations, and 606 women who had had preeClampsia during a previous pregnancy finds aspirin may reduce the incidence of the disease in women athigh risk.
Abstract: Background Whether low-dose aspirin prevents preeclampsia is unclear. It is not recommended as prophylaxis in women at low risk for preeclampsia but may reduce the incidence of the disease in women at high risk. Methods We conducted a double-blind, randomized, placebo-controlled trial in four groups of pregnant women at high risk for preeclampsia, including 471 women with pregestational insulin-treated diabetes mellitus, 774 women with chronic hypertension, 688 women with multifetal gestations, and 606 women who had had preeclampsia during a previous pregnancy. The women were enrolled between gestational weeks 13 and 26 and received either 60 mg of aspirin or placebo daily. Results Outcome data were obtained on all but 36 of the 2539 women who entered the study. The incidence of preeclampsia was similar in the 1254 women in the aspirin group and the 1249 women in the placebo group (aspirin, 18 percent; placebo, 20 percent; P = 0.23). The incidences in the aspirin and placebo groups for each of the four hi...

561 citations


Journal Article
TL;DR: Recent developments in the understanding of the antiviral and immunoregulatory properties of IFN-alpha, the nature of the multisubunit IFn-alpha receptor, and the molecular mechanisms of signal transduction are reviewed.
Abstract: IFNs were first described as potent antiviral agents 40 years ago, and recombinant IFN-alpha2a and IFN-alpha2b were approved for the treatment of hairy cell leukemia just 11 years ago Today, alpha-IFNs are approved worldwide for the treatment of a variety of malignancies and virologic diseases Although the exact mechanism of action of IFN-alpha in the treatment of such diseases is not fully understood, many advances have been made in the characterization of the physicochemical and diverse biological properties of this highly pleiotropic cytokine Here we review recent developments in our understanding of the antiviral and immunoregulatory properties of IFN-alpha, the nature of the multisubunit IFN-alpha receptor, and the molecular mechanisms of signal transduction Where available, we have included comparative data on recombinant alpha-IFNs derived from both naturally occurring and nonnaturally occurring synthetic genes We also review clinical data and data on the side effects and antigenicity of different sources of recombinant alpha-IFNs in humans These latter topics are of clinical interest, because they may potentially affect the efficacy of these various products Hopefully, what is already known about IFN will prompt further exploration into the mechanism(s) of action of IFN-alpha and thus deliver new applications for this prototypic cytokine, whose full therapeutic potential is yet to be realized

511 citations


Journal Article
TL;DR: The presence of pervasive α-synuclein deposition in the gastrointestinal tract strongly implicates this system in the pathogenesis of Parkinson's disease and holds potential for early disease detection and development of neuroprotective approaches.
Abstract: Gastrointestinal dysfunction is a frequent and occasionally dominating symptom of Parkinson's disease (PD). Features of gastrointestinal dysfunction include disordered control of saliva, dysphagia, gastroparesis, constipation in the sense of decreased bowel movement frequency, and defecatory dysfunction necessitating increased straining and resulting in incomplete evacuation. Excess saliva accumulates in the mouth because of decreased swallowing frequency. Dysphagia develops in approximately 50% of patients and may be a reflection of both central nervous system and enteric nervous system derangement. Gastroparesis may produce a variety of symptoms, including nausea, and also may be responsible for some of the motor fluctuations seen with levodopa therapy. Bowel dysfunction in PD may be the result of both delayed colon transit and impaired anorectal muscle coordination.

497 citations


Journal ArticleDOI
TL;DR: The molecular underpinnings of cerebellar development are being established through the identification of naturally occurring mutated genes and the knockout of other genes, and the process of development will ultimately be understood in terms of cellular interactions and the roles that each cell type plays in the assembly of Cerebellar structure.

497 citations


Journal ArticleDOI
TL;DR: Fetal fibronectin and a short cervix are stronger predictors of spontaneous preterm birth than traditional risk factors, and a pathway leading from Black race through bacterial vaginosis and fetal fibronsectin to spontaneous pre term birth is suggested.
Abstract: OBJECTIVES: This study was undertaken to determine the relationship between fetal fibronectin, short cervix, bacterial vaginosis, other traditional risk factors, and spontaneous preterm birth. METHODS: From 1992 through 1994, 2929 women were screened at the gestational age 22 to 24 weeks. RESULTS: The odds ratios for spontaneous preterm birth were highest for fetal fibronectin, followed by a short cervix and history of preterm birth. These factors, as well as bacterial vaginosis, were more strongly associated with early than with late spontaneous preterm birth. Bacterial vaginosis was more common--and a stronger predictor of spontaneous preterm birth--in Black women, while body mass index less than 19.8 was a stronger predictor in non-Black women. This analysis suggests a pathway leading from Black race through bacterial vaginosis and fetal fibronectin to spontaneous preterm birth. Prior preterm birth is associated with spontaneous preterm birth through a short cervix. CONCLUSIONS: Fetal fibronectin and a...

Journal ArticleDOI
TL;DR: It is reported that sustained activation by trains of several hundred presynaptic spikes resulted in much stronger depression of synaptic currents at excitatory synapses than at inhibitory ones, suggesting that inhibitory terminals of fast-spiking cells are better equipped to support prolonged transmitter release at a high frequency.
Abstract: The stability of cortical neuron activity in vivo suggests that the firing rates of both excitatory and inhibitory neurons are dynamically adjusted. Using dual recordings from excitatory pyramidal neurons and inhibitory fast-spiking neurons in neocortical slices, we report that sustained activation by trains of several hundred presynaptic spikes resulted in much stronger depression of synaptic currents at excitatory synapses than at inhibitory ones. The steady-state synaptic depression was frequency dependent and reflected presynaptic function. These results suggest that inhibitory terminals of fast-spiking cells are better equipped to support prolonged transmitter release at a high frequency compared with excitatory ones. This difference in frequency-dependent depression could produce a relative increase in the impact of inhibition during periods of high global activity and promote the stability of cortical circuits.

Journal ArticleDOI
TL;DR: Strong associations were found between current psychological distress, perfectionism and impostor feelings within each programme and these character traits were stronger predictors of psychological adjustment than most of the demographic variables associated previously with distress in health professional students.
Abstract: Extensive attention has been paid over the past three decades to the stressors involved in training in the health professions. Although empirical studies have identified demographic subgroups of students most likely to become distressed during training, less research has been carried out to evaluate the impact of students' personality characteristics on their adjustment. Severe perfectionism is one such personality trait that has been shown to increase the risk for anxiety and depressive disorders in other populations. Another set of personality traits linked to increased psychological problems has been labelled the 'impostor phenomenon', which occurs when high achieving individuals chronically question their abilities and fear that others will discover them to be intellectual frauds. Both perfectionism and the impostor phenomenon would seem to be pertinent factors in the adjustment of health professional students; however, these character traits have not been empirically examined in this population. In the present study psychological distress, perfectionism and impostor feelings were assessed in 477 medical, dental, nursing and pharmacy students. Consistent with previous reports, the results showed that a higher than expected percentage of students (27.5%) were currently experiencing psychiatric levels of distress. Strong associations were found between current psychological distress, perfectionism and impostor feelings within each programme and these character traits were stronger predictors of psychological adjustment than most of the demographic variables associated previously with distress in health professional students. Implications for future research, limitations of this study and clinical recommendations are discussed.

Journal ArticleDOI
TL;DR: The frequency of preeclampsia was not affected by the presence of proteinuria at base line, but it was greater in women who had had hypertension for at least four years (31 percent vs. 2...
Abstract: Background Women with chronic hypertension who become pregnant have an increased risk of preeclampsia and adverse neonatal outcomes. However, within this group, the risk factors for these adverse events are not known. Methods We analyzed data on outcomes for 763 women with chronic hypertension enrolled in a multicenter trial of low-dose aspirin for the prevention of preeclampsia. Preeclampsia was defined as new-onset proteinuria (urinary protein excretion, ≥300 mg per 24 hours) in the 682 women without proteinuria at base line. It was defined according to strict clinical criteria in the 81 women who had proteinuria at base line. The end points were maternal and neonatal outcomes. Results Among the 763 women, 193 (25 percent) had preeclampsia. The frequency of preeclampsia was not affected by the presence of proteinuria at base line (27 percent among women with proteinuria, vs. 25 percent among those without it), but it was greater in women who had had hypertension for at least four years (31 percent vs. 2...

Journal ArticleDOI
TL;DR: Current textbooks and the latest editions of commonly used house officer manuals use this method of determining maintenance water needs based on calorie expenditure for estimating insensible and urinary water losses of children and adults of any size or age.
Abstract: In the category of genitourinary and fluid and electrolyte disorders, no paper bridges the discoveries of the 1930s through the 1950s and the practice of today as does the classic paper of Holliday and Segar.1 Today house officers and staff physicians use this same simple method for estimating insensible and urinary water losses of a child or adult of any size or age. Current textbooks and the latest editions of commonly used house officer manuals use this method of determining maintenance water needs based on calorie expenditure.2-5 This method involves a simple formula that relates the average calorie expenditure of a … Address correspondence to Russell W. Chesney, MD, University of Tennessee, Memphis; Le Bonheur Children's Medical Center, 50 N Dunlap, Room 306, Memphis, TN 38103.

Journal ArticleDOI
TL;DR: Late onset septicemia is common in very low birth weight infants, and the rate is inversely proportional to gestational age and birth weight, but they have poor positive predictive value.
Abstract: Background.Septicemia is a major antecedent of morbidity and mortality in very low birth weight (501- to 1500-g) infants. Our purpose was to determine prospectively the incidence, clinical presentation, laboratory features, risk factors, morbidity and mortality associated with late onset septicem

Journal ArticleDOI
TL;DR: The range of cell processes regulated by anti-sigma factors is highly varied and includes bacteriophage phage growth, sporulation, stress response, flagellar biosynthesis, pigment production, ion transport, and virulence.
Abstract: ▪ Abstract A mechanism for regulating gene expression at the level of transcription utilizes an antagonist of the sigma transcription factor known as the anti-sigma (anti-σ) factor. The cytoplasmic class of anti-σ factors has been well characterized. The class includes AsiA form bacteriophage T4, which inhibits Escherichia coli σ70; FlgM, present in both gram-positive and gram-negative bacteria, which inhibits the flagella sigma factor σ28; SpoIIAB, which inhibits the sporulation-specific sigma factors, σF and σG, of Bacillus subtilis; RbsW of B. subtilis, which inhibits stress response sigma factor σB; and DnaK, a general regulator of the heat shock response, which in bacteria inhibits the heat shock sigma factor σ32. In addition to this class of well-characterized cytoplasmic anti-sigma factors, a new class of homologous, inner-membrane–bound anti-σ factors has recently been discovered in a variety of eubacteria. This new class of anti-σ factors regulates the expression of so-called extracytoplasmic fun...

Journal ArticleDOI
TL;DR: Results indicate that Dab1 functions downstream of Reln in a signaling pathway that controls cell positioning in the developing brain.
Abstract: Mutation of either reelin (Reln) or disabled-1 (Dab1) results in widespread abnormalities in laminar structures throughout the brain and ataxia in reeler and scrambler mice. Both exhibit the same neuroanatomical defects, including cerebellar hypoplasia with Purkinje cell ectopia and disruption of neuronal layers in the cerebral cortex and hippocampus. Despite these phenotypic similarities, Reln and Dab1 have distinct molecular properties. Reln is a large extracellular protein secreted by Cajal-Retzius cells in the forebrain and by granule neurons in the cerebellum. In contrast, Dab1 is a cytoplasmic protein which has properties of an adapter protein that functions in phosphorylation-dependent intracellular signal transduction. Here, we show that Dab1 participates in the same developmental process as Reln. In scrambler mice, neuronal precursors are unable to invade the preplate of the cerebral cortex and consequently, they do not align within the cortical plate. During development, cells expressing Dab1 are located next to those secreting Reln at critical stages of formation of the cerebral cortex, cerebellum and hippocampus, before the first abnormalities in cell position become apparent in either reeler or scrambler. In reeler, the major populations of displaced neurons contain elevated levels of Dab1 protein, although they express normal levels of Dab1 mRNA. This suggests that Dab1 accumulates in the absence of a Reln-evoked signal. Taken together, these results indicate that Dab1 functions downstream of Reln in a signaling pathway that controls cell positioning in the developing brain.

Journal ArticleDOI
TL;DR: In this paper, it was shown that genetic variation in an originally commensal trait, the FimH lectin of type 1 fimbriae, can change the tropism of Escherichia coli, shifting it toward a urovirulent phenotype.
Abstract: Conventional wisdom regarding mechanisms of bacterial pathogenesis holds that pathogens arise by external acquisition of distinct virulence factors, whereas determinants shared by pathogens and commensals are considered to be functionally equivalent and have been ignored as genes that could become adapted specifically for virulence. It is shown here, however, that genetic variation in an originally commensal trait, the FimH lectin of type 1 fimbriae, can change the tropism of Escherichia coli, shifting it toward a urovirulent phenotype. Random point mutations in fimH genes that increase binding of the adhesin to mono-mannose residues, structures abundant in the oligosaccharide moieties of urothelial glycoproteins, confer increased virulence in the mouse urinary tract. These mutant FimH variants, however, are characterized by increased sensitivity to soluble inhibitors bathing the oropharyngeal mucosa, the physiological portal of E. coli. This functional trade-off seems to be detrimental for the intestinal ecology of the urovirulent E. coli. Thus, bacterial virulence can be increased by random functional mutations in a commensal trait that are adaptive for a pathologic environment, even at the cost of reduced physiological fitness in the nonpathologic habitat.

Journal ArticleDOI
TL;DR: The basal ganglia appears to have undergone a major elaboration during the evolutionary transition from amphibians to reptiles, which may have enabled amniotes to learn and/or execute a more sophisticated repertoire of behaviors and movements, and this ability may have been an important element of the successful adaptation of amniots to a fully terrestrial habitat.

Journal ArticleDOI
TL;DR: Results contradict the view that these compounds directly disrupt membranes and suggest that their widespread use will select for resistant bacterial populations.

Journal ArticleDOI
TL;DR: Phylogenetic analyses indicate that HEV US-1 and a recently discovered HEV variant from swine may represent separate isolates of a new strain of HEV, significantly divergent from the Mexican and Burmese strains.
Abstract: A variant of hepatitis E virus (HEV), designated HEV US-1, was identified in a hepatitis patient in the United States (US); the patient had no history of travel to areas where HEV is endemic. Nucleotide sequences were obtained from the 5' end of open reading frame (ORF) 1 (1418 nt), the 3' end of ORF1 (1359 nt), the entire ORF2 and ORF3 regions, and the 3'-untranslated region (2127 nt). The HEV US-1 strain is significantly divergent from other human HEV isolates with nucleotide identities ranging from 76.8 to 77.5%. Phylogenetic analyses indicate that HEV US-1 and a recently discovered HEV variant from swine may represent separate isolates of a new strain of HEV, significantly divergent from the Mexican and Burmese strains. Synthetic peptides derived from the carboxyl amino acids of ORF2 and ORF3 were shown to be useful for detecting exposure to HEV. In addition, IgM class antibodies directed against HEV US-1 synthetic peptides were detected in the US patient infected with HEV US-1, but were absent using synthetic peptides from the Burmese or Mexican strains of HEV. A preferential reactivity to HEV US-1 specific peptides has lead to the identification of a second isolate of this virus also from a patient with acute hepatitis from the US. The discovery of these HEV variants may be important in understanding the worldwide distribution of HEV infection.

Journal ArticleDOI
TL;DR: HCTT is sensitive for diagnosing intimal injuries and pseudoaneurysms and early diagnosis with HCTT and presumptive treatment with the antihypertensive regimen eliminated in-hospital aortic rupture.
Abstract: OBJECTIVE: There were two aims of this study The first was to evaluate the application of helical computed tomography of the thorax (HCTT) for the diagnosis of blunt aortic injury (BAI) The second was to evaluate the efficacy of beta-blockers with or without nitroprusside in preventing aortic rupture SUMMARY BACKGROUND DATA: Aortography has been the standard for diagnosing BAI for the past 4 decades Conventional chest CT has not proven to be of significant value Helical CT scanning is faster and has higher resolution than conventional CT Retrospective studies have suggested the efficacy of antihypertensives in preventing aortic rupture METHODS: A prospective study comparing HCTT to aortography in the diagnosis of BAI was performed A protocol of beta-blockers with or without nitroprusside was also examined for efficacy in preventing rupture before aortic repair and in allowing delayed repair in patients with significant associated injuries RESULTS: Over a period of 4 years, 494 patients were studied BAI was diagnosed in 71 patients Sensitivity was 100% for HCTT versus 92% for aortography Specificity was 83% for HCTT versus 99% for aortography Accuracy was 86% for HCTT versus 97% for aortography Positive predictive value was 50% for HCTT versus 97% for aortography Negative predictive value was 100% for HCTT versus 97% for aortography No patient had spontaneous rupture in this study CONCLUSIONS: HCTT is sensitive for diagnosing intimal injuries and pseudoaneurysms Patients without direct HCTT evidence of BAI require no further evaluation Aortography can be reserved for indeterminate HCTT scans Early diagnosis with HCTT and presumptive treatment with the antihypertensive regimen eliminated in-hospital aortic rupture

Journal ArticleDOI
TL;DR: Depression was associated with a generally increased risk of cancer when present for at least 6 years and was consistent for most types of cancer and was not specific to cigarette smokers.
Abstract: Background: Depression has been proposed as a predisposing factor for cancer, but prospective studies have been inconclusive. We examined whether a high level of depressive symptoms, present for a long time, is associated with increased risk of cancer in the elderly. Methods: Data were obtained and analyzed from persons who lived in three communities (Massachusetts, Iowa, and Connecticut) of the Established Populations for Epidemiologic Studies of the Elderly, a prospective cohort study with a mean follow-up of 3.8 years that included 4825 persons (1708 men and 3117 women) aged 71 years and older. Chronically depressed mood was defined as present when the number of depressive symptoms exceeded specific cut points on the Center for Epidemiologic Studies-Depression scale at baseline (1988) and 3 and 6 years before baseline. New cases of cancer were identified from Medicare hospitalization records and death certificates. Results: Of the 4825 persons studied, 146 (3.0%) were chronically depressed. The incidence rate of cancer was 30.5 per 1000 person-years for the 146 persons with chronic depression and 21.9 per 1000 person-years for the 4679 nonchronically depressed persons. After adjustment for age, sex, race, disability, hospital admissions, alcohol intake, and smoking, the hazard ratio for cancer associated with chronically depressed mood was 1.88 (95% confidence interval = 1.13-3.14). The excess risk of cancer associated with chronic depression was consistent for most types of cancer and was not specific to cigarette smokers. Conclusion: When present for at least 6 years, depression was associated with a generally increased risk of cancer.

Journal ArticleDOI
TL;DR: Results suggest that GEF-H1 may have a direct role in activation of Rac and/or Rho and in bringing the activated GTPase to specific target sites such as microtubules.

Journal ArticleDOI
TL;DR: In this article, the authors evaluated clinical outcomes and established the incidence and management of a hypertensive phase (defined as intraocular pressure [IOP] > 21 mmHg in the first 6 postoperative months) in patients with Ahmed glaucoma valve implant.

Journal ArticleDOI
TL;DR: The data suggest that VEGF may modulate endothelial cell-derived MMP activity by increasing the abundance of gelatinase A; disinhibiting gelatinases A by decreasing the abundanceof TIMP-2; and disinhibititing preexisting collagenase by reducing levels of TIMP -1.

Journal ArticleDOI
TL;DR: Striatal neurons with totally overlapping dendritic volumes have few presynaptic cortical axons in common, and cortical cells with overlapping axons have few striatal target neurons in common; these results explain the absence of redundancy in the responses of neurons located near each other in the striatum.
Abstract: The distribution of synapses formed by corticostriatal neurons was measured to determine the average connectivity and degree of convergence of these neurons and to search for spatial inhomogeneities. Two kinds of axonal fields, focal and extended, and two striatal tissue compartments, the patch (striosome) and matrix, were analyzed separately. Electron microscopic examination revealed that both kinds of corticostriatal axons made synapses at varicosities that could be identified in the light microscope, and each varicosity made a single synapse. Thus, the distribution of varicosities was a good estimate of the spatial distribution of synapses. The distance between axonal varicosities was measured to determine the density of synaptic connections formed by one axon within the volume occupied by a striatal neuron. Intersynaptic distances were distributed exponentially, except that synapses were rarely located

Journal ArticleDOI
TL;DR: Thymoglobulin was found to be superior to Atgam in reversing acute rejection and preventing recurrent rejection after therapy in renal transplant recipients.
Abstract: Background. Thymoglobulin, a rabbit anti-human thymocyte globulin, was compared with Atgam, a horse anti-human thymocyte globulin for the treatment of acute rejection after renal transplantation. Methods. A multicenter, double-blind, randomized trial with enrollment stratification based on standardized histology (Banff grading) was conducted. Subjects received 7-14 days of Thymoglobulin (1.5 mg/kg/ day) or Atgam (15 mg/kg/day). The primary end point was rejection reversal (return of serum creatinine level to or below the day 0 baseline value). Results. A total of 163 patients were enrolled at 25 transplant centers in the United States. No differences in demographics or transplant characteristics were noted. Intent-to-treat analysis demonstrated that Thymoglobulin had a higher rejection reversal rate than Atgam (88% versus 76%, P=0.027, primary end point). Day 30 graft survival rates (Thymoglobulin 94% and Atgam 90%, P=0.17), day 30 serum creatinine levels as a percentage of baseline (Thymoglobulin 72% and Atgam 80%; P=0.43), and improvement in posttreatment biopsy results (Thymoglobulin 65% and Atgam 50%; P=0.15) were not statistically different. T-cell depletion was maintained more effectively with Thymoglobulin than Atgam both at the end of therapy (P=0.001) and at day 30 (P=0.016). Recurrent rejection, at 90 days after therapy, occurred less frequently with Thymoglobulin (17%) versus Atgam (36%) (P=0.011).

Journal ArticleDOI
01 May 1998-Oncogene
TL;DR: The present observations suggest that the anti-transformation effects of radicicol may be mediated, at least in part, by the association of Radicicol with HSP90 and the consequent dissociation of the Raf/HSP90 complex leading to the attenuation of the Ras/MAP kinase signal transduction pathway.
Abstract: Radicicol, a macrocyclic anti-fungal antibiotic, has the ability to suppress transformation by diverse oncogenes such as Src, Ras and Mos. Despite this useful property, the mechanism by which radicicol exerts its anti-transformation effects is currently unknown. To understand the transformation-suppressing effects of radicicol, a biotinylated derivative of radicicol was chemically synthesized and used as a probe in a Western-blot format to visualize cellular proteins that interact with radicicol. In transformed and untransformed mouse fibroblasts, the most prominent cellular protein that bound to radicicol had a molecular weight of approximately 90 kDa. Further analysis revealed that this protein was the mouse homologue of the 90 kDa heat shock protein (HSP90). This was confirmed by demonstrating the ability of radicicol to specifically bind purified human HSP90. Specificity of binding was demonstrated by the inhibition of binding of biotinylated radicicol by the native drug. Taken together with other studies the present observations suggest that the anti-transformation effects of radicicol may be mediated, at least in part, by the association of radicicol with HSP90 and the consequent dissociation of the Raf/HSP90 complex leading to the attenuation of the Ras/MAP kinase signal transduction pathway.