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Showing papers by "Medical University of South Carolina published in 2000"


Journal ArticleDOI
17 Mar 2000-Cell
TL;DR: T-bet initiates Th1 lineage development from naive Thp cells both by activating Th1 genetic programs and by repressing the opposing Th2 programs, as evidenced by the simultaneous induction of IFNgamma and repression of IL-4 and IL-5.

3,479 citations


Journal ArticleDOI
TL;DR: Hospital or nursing home confinement, surgery, trauma, malignant neoplasm, chemotherapy, neurologic disease with paresis, central venous catheter or pacemaker, varicose veins, and superficial vein thrombosis are independent and important risk factors for VTE.
Abstract: Background Reported risk factors for venous thromboembolism (VTE) vary widely, and the magnitude and independence of each are uncertain Objectives To identify independent risk factors for deep vein thrombosis and pulmonary embolism and to estimate the magnitude of risk for each Patients and Methods We performed a population-based, nested, case-control study of 625 Olmsted County, Minnesota, patients with a first lifetime VTE diagnosed during the 15-year period from January 1, 1976, through December 31, 1990, and 625 Olmsted County patients without VTE The 2 groups were matched on age, sex, calendar year, and medical record number Results Independent risk factors for VTE included surgery (odds ratio [OR], 217; 95% confidence interval [CI], 94-499), trauma (OR, 127; 95% CI, 41-397), hospital or nursing home confinement (OR, 80; 95% CI, 45-142), malignant neoplasm with (OR, 65; 95% CI, 21-202) or without (OR, 41; 95% CI, 19-85) chemotherapy, central venous catheter or pacemaker (OR, 56; 95% CI, 16-196), superficial vein thrombosis (OR, 43; 95% CI, 18-106), and neurological disease with extremity paresis (OR, 30; 95% CI, 13-74) The risk associated with varicose veins diminished with age (for age 45 years: OR, 42; 95% CI, 16-113; for age 60 years: OR, 19; 95% CI, 10-36; for age 75 years: OR, 09; 95% CI, 06-14), while patients with liver disease had a reduced risk (OR, 01; 95% CI, 00-07) Conclusion Hospital or nursing home confinement, surgery, trauma, malignant neoplasm, chemotherapy, neurologic disease with paresis, central venous catheter or pacemaker, varicose veins, and superficial vein thrombosis are independent and important risk factors for VTE

2,069 citations


Journal ArticleDOI
TL;DR: The distinctions between drugs in the induction and expression of sensitization indicate that behavioral sensitization can arise from multiple neuroadaptations in multiple brain nuclei, not only the result of distinct molecular targets for the drugs, but may also include a differential involvement of learned associations.
Abstract: Rationale and objectives: Repeated exposure to many drugs of abuse results in a progressive and enduring enhancement in the motor stimulant effect elicited by a subsequent drug challenge. This phenomenon, termed behavioral sensitization, is thought to underlie certain aspects of drug addiction. Behavioral sensitization is the consequence of drug-induced neuroadaptive changes in a circuit involving dopaminergic and glutamatergic interconnections between the ventral tegmental area, nucleus accumbens, prefrontal cortex and amygdala. Methods: The literature was critically reviewed in an effort to discern the relative roles of glutamate and dopamine transmission in the induction and expression of sensitization to amphetamine, cocaine and µ-opioids. In addition, the literature was reviewed to evaluate distinctions between these drugs in the involvement of the relevant brain nuclei listed above. Results: The common substrates between sensitizing drugs are glutamate transmission, especially at the NMDA receptor, and an action in the ventral tegmental area. In contrast, a role for dopamine is only clearly seen in amphetamine sensitization and critical involvement of nuclei outside the ventral tegmental area is found for cocaine and morphine. While enhanced dopamine transmission is associated with sensitization by all three drugs, a role for glutamate is clearly identified only with cocaine sensitization. Accordingly, glutamatergic cortical and allocortical brain regions such as the prefrontal cortex appear more critical for cocaine sensitization. Conclusions: The distinctions between drugs in the induction and expression of sensitization indicate that behavioral sensitization can arise from multiple neuroadaptations in multiple brain nuclei. This is not only the result of distinct molecular targets for the drugs, but may also include a differential involvement of learned associations. It is postulated that the relatively more robust pharmacological capacity of amphetamine to release dopamine may induce a form of sensitization that is more dependent on adaptations in mesoaccumbens dopamine transmission compared with cocaine and morphine sensitization.

1,327 citations


Journal ArticleDOI
TL;DR: The results demonstrate the importance of HA in mammalian embryogenesis and the pivotal role of Has2 during mammalian development and reveal a previously unrecognized pathway for cell migration and invasion that is HA-dependent and involves Ras activation.
Abstract: We identified hyaluronan synthase-2 (Has2) as a likely source of hyaluronan (HA) during embryonic development, and we used gene targeting to study its function in vivo. Has2(-/-) embryos lack HA, exhibit severe cardiac and vascular abnormalities, and die during midgestation (E9.5-10). Heart explants from Has2(-/-) embryos lack the characteristic transformation of cardiac endothelial cells into mesenchyme, an essential developmental event that depends on receptor-mediated intracellular signaling. This defect is reproduced by expression of a dominant-negative Ras in wild-type heart explants, and is reversed in Has2(-/-) explants by gene rescue, by administering exogenous HA, or by expressing activated Ras. Conversely, transformation in Has2(-/-) explants mediated by exogenous HA is inhibited by dominant-negative Ras. Collectively, our results demonstrate the importance of HA in mammalian embryogenesis and the pivotal role of Has2 during mammalian development. They also reveal a previously unrecognized pathway for cell migration and invasion that is HA-dependent and involves Ras activation.

856 citations


Journal ArticleDOI
TL;DR: First experimental evidence that protein turnover is a major determinant in AGE accumulation in different collagen types is provided, thereby providing the first reasonable estimates of the half-lives of these collagens.

805 citations


Journal Article
TL;DR: Comorbidity in PTSD is the rule rather than the exception and this area warrants much further study since comorbid conditions may provide a rationale for the subtyping of individuals with PTSD to optimize treatment outcomes.
Abstract: Posttraumatic stress disorder (PTSD) commonly co-occurs with other psychiatric disorders. Data from epidemiologic surveys indicate that the vast majority of individuals with PTSD meet criteria for at least one other psychiatric disorder, and a substantial percentage have 3 or more other psychiatric diagnoses. A number of different hypothetical constructs have been posited to explain this high comorbidity; for example, the self-medication hypothesis has often been applied to understand the relationship between PTSD and substance use disorders. There is a substantial amount of symptom overlap between PTSD and a number of other psychiatric diagnoses, particularly major depressive disorder. It has been suggested that high rates of comorbidity may be simply an epiphenomenon of the diagnostic criteria used. In any case, this high degree of symptom overlap can contribute to diagnostic confusion and, in particular, to the underdiagnosis of PTSD when trauma histories are not specifically obtained. The most common comorbid diagnoses are depressive disorders, substance use disorders, and other anxiety disorders. The comorbidity of PTSD and depressive disorders is of particular interest. Across a number of studies, these are the disorders most likely to co-occur with PTSD. It is also clear that depressive disorder can be a common and independent sequela of exposure to trauma and having a previous depressive disorder is a risk factor for the development of PTSD once exposure to a trauma occurs. The comorbidity of PTSD with substance use disorders is complex because while a substance use disorder may often develop as an attempt to self-medicate the painful symptoms of PTSD, withdrawal states exaggerate these symptoms. Appropriate treatment of PTSD in substance abusers is a controversial issue because of the belief that addressing issues related to the trauma in early recovery can precipitate relapse. In conclusion, comorbidity in PTSD is the rule rather than the exception. This area warrants much further study since comorbid conditions may provide a rationale for the subtyping of individuals with PTSD to optimize treatment outcomes.

762 citations


Journal ArticleDOI
TL;DR: The recommendations are distilled in this summary, but the reader is encouraged to review the more extensive discussions in subsequent sections, which show the strength of the recommendations and the quality of the evidence.
Abstract: Aspergillosis comprises a variety of manifestations of infection. These guidelines are directed to 3 principal entities: invasive aspergillosis, involving several organ systems (particularly pulmonary disease); pulmonary aspergilloma; and allergic bronchopulmonary aspergillosis. The recommendations are distilled in this summary, but the reader is encouraged to review the more extensive discussions in subsequent sections, which show the strength of the recommendations and the quality of the evidence, and the original publications cited in detail. Invasive aspergillosis. Because it is highly lethal in the immunocompromised host, even in the face of therapy, work-up must be prompt and aggressive, and therapy may need to be initiated upon suspicion of the diagnosis, without definitive proof (BIII). Intravenous therapy should be used initially in rapidly progressing disease (BIII). The largest therapeutic experience is with amphotericin B deoxycholate, which should be given at maximum tolerated doses (e.g., 1-1.5 mg/kg/d) and should be continued, despite modest increases in serum creatinine levels (BIII). Lipid formulations of amphotericin are indicated for the patient who has impaired renal function or who develops nephrotoxicity while receiving deoxycholate amphotericin (AII). Oral itraconazole is an alternative for patients who can take oral medication, are likely to be adherent, can be demonstrated (by serum level monitoring) to absorb the drug, and lack the potential for interaction with other drugs (BII). Oral itraconazole is attractive for continuing therapy in the patient who responds to initial iv therapy (CIII). Therapy should be prolonged beyond resolution of disease and reversible underlying predispositions (BIII). Adjunctive therapy (particularly surgery and combination chemotherapy, also immunotherapy), may be useful in certain situations (CIII). Aspergilloma. The optimal treatment strategy for aspergilloma is unknown. Therapy is predominantly directed at preventing life-threatening hemoptysis. Surgical removal of aspergilloma is definitive treatment, but because of significant morbidity and mortality it should be reserved for high-risk patients such as those with episodes of life-threatening hemoptysis, and considered for patients with underlying sarcoidosis, immunocompromised patients, and those with increasing Aspergillus-specific IgG titers (CIII). Surgical candidates would need to have adequate pulmonary function to undergo the operation. Bronchial artery embolization rarely produces a permanent success, but may be useful as a temporizing procedure in patients with life-threatening hemoptysis. Endobronchial and intracavitary instillation of antifungals or oral itraconazole may be useful for this condition. Since the majority of aspergillomas do not cause life-threatening hemoptysis, the morbidity and cost of treatment must be weighed against the clinical benefit. Allergic bronchopulmonary aspergillosis (APBA). Although no well-designed studies have been carried out, the available data support the use of corticosteroids for acute exacerbations of ABPA (AII). Neither the optimal corticosteroid dose nor the duration of therapy has been standardized, but limited data suggest the starting dose should be approximately 0.5 mg/kg/d of prednisone. The decision to taper corticosteroids should be made on an individual basis, depending on the clinical course (BIII). The available data suggest that clinical symptoms alone are inadequate to make such decisions, since significant lung damage may occur in asymptomatic patients. Increasing serum IgE levels, new or worsening infiltrate on chest radiograph, and worsening spirometry suggest that corticosteroids should be used (BII). Multiple asthmatic exacerbations in a patient with ABPA suggest that chronic corticosteroid therapy should be used (BIII). Itraconazole appears useful as a corticosteroid sparing agent (BII). (ABSTRACT TRUNCATED)

754 citations


Journal ArticleDOI
TL;DR: Several extracellular agents and stress stimuli, such as tumour necrosis factor alpha, chemotherapeutic agents and heat, cause ceramide accumulation by regulating enzymes involved in its metabolism.

729 citations


Journal ArticleDOI
12 Apr 2000-JAMA
TL;DR: The data suggest that sertraline is a safe, well-tolerated, and effective treatment for PTSD.
Abstract: ContextDespite the high prevalence, chronicity, and associated comorbidity of posttraumatic stress disorder (PTSD) in the community, few placebo-controlled studies have evaluated the efficacy of pharmacotherapy for this disorder.ObjectiveTo determine if treatment with sertraline hydrochloride effectively diminishes symptoms of PTSD of moderate to marked severity.DesignTwelve-week, double-blind, placebo-controlled trial preceded by a 2-week, single-blind placebo lead-in period, conducted between May 1996 and June 1997.SettingOutpatient psychiatric clinics in 8 academic medical centers and 6 clinical research centers.PatientsA total of 187 outpatients with a Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition diagnosis of PTSD and a Clinician Administered PTSD Scale Part 2 (CAPS-2) minimum total severity score of at least 50 at baseline (mean age, 40 years; mean duration of illness, 12 years; 73% were women; and 61.5% experienced physical or sexual assault).InterventionPatients were randomized to acute treatment with sertraline hydrochloride in flexible daily dosages of 50 to 200 mg/d, following 1 week at 25 mg/d (n=94); or placebo (n=93).Main Outcome MeasuresBaseline-to-end-point changes in CAPS-2 total severity score, Impact of Event Scale total score (IES), and Clinical Global Impression–Severity (CGI-S), and CGI-Improvement (CGI-I) ratings, compared by treatment vs placebo groups.ResultsSertraline treatment yielded significantly greater improvement than placebo on 3 of the 4 primary outcome measures (mean change from baseline to end point for CAPS-2 total score, −33.0 vs −23.2 [P=.02], and for CGI-S, −1.2 vs −0.8 [P=.01]; mean CGI-I score at end point, 2.5 vs 3.0 [P=.02]), with the fourth measure, the IES total score, showing a trend toward significance (mean change from baseline to end point, −16.2 vs −12.1; P=.07). Using a conservative last-observation-carried-forward analysis, treatment with sertraline resulted in a responder rate of 53% at study end point compared with 32% for placebo (P=.008, with responder defined as >30% reduction from baseline in CAPS-2 total severity score and a CGI-I score of 1 [very much improved], or 2 [much improved]). Significant (P<.05) efficacy was evident for sertraline from week 2 on the CAPS-2 total severity score. Sertraline had significant efficacy vs placebo on the CAPS-2 PTSD symptom clusters of avoidance/numbing (P=.02) and increased arousal (P=.03) but not on reexperiencing/intrusion (P=.14). Sertraline was well tolerated, with insomnia the only adverse effect reported significantly more often than placebo (16.0% vs 4.3%; P=.01).ConclusionsOur data suggest that sertraline is a safe, well-tolerated, and effective treatment for PTSD.

642 citations


Journal ArticleDOI
TL;DR: Treatment with metronidazole did not reduce the occurrence of preterm labor, intraamniotic or postpartum infections, neonatal sepsis, or admission of the infant to the neonatal intensive care unit.
Abstract: Background Bacterial vaginosis has been associated with preterm birth. In clinical trials, the treatment of bacterial vaginosis in pregnant women who previously had a preterm delivery reduced the risk of recurrence. Methods To determine whether treating women in a general obstetrical population who have asymptomatic bacterial vaginosis (as diagnosed on the basis of vaginal Gram's staining and pH) prevents preterm delivery, we randomly assigned 1953 women who were 16 to less than 24 weeks pregnant to receive two 2-g doses of metronidazole or placebo. The diagnostic studies were repeated and a second treatment was administered to all the women at 24 to less than 30 weeks' gestation. The primary outcome was the rate of delivery before 37 weeks' gestation. Results Bacterial vaginosis resolved in 657 of 845 women who had follow-up Gram's staining in the metronidazole group (77.8 percent) and 321 of 859 women in the placebo group (37.4 percent). Data on the time and characteristics of delivery were available fo...

602 citations


Journal ArticleDOI
01 Feb 2000-Chest
TL;DR: Overall survival was statistically superior for the patients receiving chemotherapy and radiation vs the other two arms of the study, and the twice-daily radiation therapy arm, although better, was not statistically superior in survival for those patients receiving standard radiation.

Journal ArticleDOI
TL;DR: It is concluded that experimental studies uncovering the rules of myocardial assembly are relevant for the full understanding of development of the human heart.
Abstract: The heart in higher vertebrates develops from a simple tube into a complex organ with four chambers specialized for efficient pumping at pressure. During this period, there is a concomitant change in the level of myocardial organization. One important event is the emergence of trabeculations in the luminal layers of the ventricles, a feature which enables the myocardium to increase its mass in the absence of any discrete coronary circulation. In subsequent development, this trabecular layer becomes solidified in its deeper part, thus increasing the compact component of the ventricular myocardium. The remaining layer adjacent to the ventricular lumen retains its trabeculations, with patterns which are both ventricle- and species-specific. During ontogenesis, the compact layer is initially only a few cells thick, but gradually develops a multilayered spiral architecture. A similar process can be charted in the atrial myocardium, where the luminal trabeculations become the pectinate muscles. Their extent then provides the best guide for distinguishing intrinsically the morphologically right from the left atrium. We review the variations of these processes during the development of the human heart and hearts from commonly used laboratory species (chick, mouse, and rat). Comparison with hearts from lower vertebrates is also provided. Despite some variations, such as the final pattern of papillary or pectinate muscles, the hearts observe the same biomechanical rules, and thus share many common points. The functional importance of myocardial organization is demonstrated by lethality of mouse mutants with perturbed myocardial architecture. We conclude that experimental studies uncovering the rules of myocardial assembly are relevant for the full understanding of development of the human heart.


Journal ArticleDOI
TL;DR: An animal model of relapse was used to demonstrate that glutamate, and not dopamine transmission in the nucleus accumbens, is a primary mediator of cocaine-induced reinstatement of drug-seeking behavior.
Abstract: Elevated dopamine transmission in the nucleus accumbens is thought to be a primary mediator of addiction to cocaine. However, repeated exposure to cocaine is associated with the recruitment of glutamate transmission. This poses the possibility that the behaviors characterizing cocaine addiction, such as craving-induced relapse, may not be preferentially mediated by dopamine transmission. An animal model of relapse was used to demonstrate that glutamate, and not dopamine transmission in the nucleus accumbens, is a primary mediator of cocaine-induced reinstatement of drug-seeking behavior. Reinstatement was produced by a systemic injection of cocaine or by the microinjection of the glutamate receptor agonist AMPA or dopamine into the nucleus accumbens. It was found that microinjection of an AMPA receptor antagonist into the nucleus accumbens blocked reinstatement by all compounds, whereas a dopamine receptor antagonist was effective only in blocking reinstatement by intra-accumbens dopamine administration. These data suggest an important role for nucleus accumbens glutamate and not dopamine transmission in cocaine-induced relapse to drug-seeking behavior.

Journal ArticleDOI
TL;DR: NIRS can be used in a noninvasive manner at the bedside to identify premature infants with impaired cerebrovascular autoregulation, which is relatively common in such infants, and that the presence of this impairment is associated with a high likelihood of occurrence of severe GMH-IVH/PVL.
Abstract: Objectives. Premature infants experience brain injury, ie, germinal matrix–intraventricular hemorrhage (GMH-IVH) and periventricular leukomalacia (PVL), in considerable part because of disturbances in cerebral blood flow (CBF). Because such infants are susceptible to major fluctuations in mean arterial blood pressure (MAP), impaired cerebrovascular autoregulation would increase the likelihood for the changes in CBF that could result in GMH-IVH and PVL. The objectives of this study were to determine whether a state of impaired cerebrovascular autoregulation could be identified reliably and conveniently at the bedside, the frequency of any such impairment, and the relation of the impairment to the subsequent occurrence of severe GMH-IVH and PVL. Patients and Methods. To monitor the cerebral circulation continuously and noninvasively, we used near-infrared spectroscopy (NIRS) to determine quantitative changes in cerebral concentrations of oxygenated hemoglobin (HbO2) and deoxygenated hemoglobin (Hb) from the first hours of life. Our previous experimental study showed a strong correlation between a measure of cerebral intravascular oxygenation (HbD), ie, HbD = HbO2 − Hb, determined by NIRS, and volemic CBF, determined by radioactive microspheres. We studied 32 very low birth weight premature infants (gestational age: 23–31 weeks; birth weight: 605-1870 g) requiring mechanical ventilation, supplemental oxygen, and invasive blood pressure monitoring by NIRS from 1 to 3 days of age. MAP measured by arterial catheter pressure transducer and arterial oxygen saturation measured by pulse oximetry were recorded simultaneously. The relationship of MAP to HbD was quantitated by coherence analysis. Results. Concordant changes (coherence scores >.5) in HbD and MAP, consistent with impaired cerebrovascular autoregulation, were observed in 17 of the 32 infants (53%). Eight of the 17 infants (47%) developed severe GMH-IVH or PVL or both. Of the 15 infants with apparently intact autoregulation, ie, coherence scores .5. Conclusions. We conclude that NIRS can be used in a noninvasive manner at the bedside to identify premature infants with impaired cerebrovascular autoregulation, that this impairment is relatively common in such infants, and that the presence of this impairment is associated with a high likelihood of occurrence of severe GMH-IVH/PVL.

Journal ArticleDOI
TL;DR: XBP-1 is a CREB/ATF family transcription factor highly expressed in hepatocellular carcinomas that is essential for liver growth and specific target genes of XBP- 1 in the liver were identified as alphaFP, which may be a regulator of hepatocyte growth, and three acute phase protein family members.
Abstract: XBP-1 is a CREB/ATF family transcription factor highly expressed in hepatocellular carcinomas. Here we report that XBP-1 is essential for liver growth. Mice lacking XBP-1 displayed hypoplastic fetal livers, whose reduced hematopoiesis resulted in death from anemia. Nevertheless, XBP-1-deficient hematopoietic progenitors had no cell-autonomous defect in differentiation. Rather, hepatocyte development itself was severely impaired by two measures: diminished growth rate and prominent apoptosis. Specific target genes of XBP-1 in the liver were identified as aFP, which may be a regulator of hepatocyte growth, and three acute phase protein family members. Therefore, XBP-1 is a transcription factor essential for hepatocyte growth.

Journal ArticleDOI
01 Mar 2000-Gut
TL;DR: The overall incidence rate of ulcerative colitis in Olmsted County increased until the 1970s, and remained stable thereafter, and was similar to that of the general population.
Abstract: BACKGROUND There is significant geographic variation in the reported incidence of ulcerative colitis. AIMS To update the incidence and prevalence of ulcerative colitis in Olmsted County, Minnesota, examine temporal trends, and determine overall survival. PATIENTS All Olmsted County residents diagnosed with ulcerative colitis between 1940 and 1993 (incidence cases), and all residents with ulcerative colitis alive on 1 January 1991 (prevalence cases). METHODS Incidence and prevalence rates were adjusted using 1990 US census figures for whites. The effects of age, sex, and calendar year on incidence rates were evaluated using Poisson regression. Survival from diagnosis was compared with that expected for US north-central whites. RESULTS Between 1940 and 1993, 278 incidence cases were identified, for an adjusted incidence rate of 7.6 cases per 100 000 person years (95% confidence interval (CI), 6.7 to 8.5). On 1 January 1991, there were 218 residents with definite or probable ulcerative colitis, for an adjusted prevalence rate of 229 cases per 100 000 (95% CI, 198 to 260). Increased incidence rates were associated with later calendar years (p 0.2). CONCLUSIONS The overall incidence rate of ulcerative colitis in Olmsted County increased until the 1970s, and remained stable thereafter. Incidence rates among men and urban residents were significantly higher. The prevalence rate in Rochester in 1991 was 19% higher than that in 1980. Overall survival was similar to that of the general population.

Journal ArticleDOI
TL;DR: Increased LV myocardial MMP activity and selective upregulation of MMPs with nonischemic and ischemic forms of DCM occurred and a local MMP induction/activation system was identified in isolated normal human LV myocytes that was upregulated with DCM.
Abstract: Background—Matrix metalloproteinases (MMPs) contribute to matrix remodeling in disease states such as tumor metastases. Extracellular matrix metalloproteinase inducer (EMMPRIN) has been reported to...

Journal ArticleDOI
TL;DR: Therapist adherence to the MST protocol was associated with improved family relations and decreased delinquent peer affiliation, which were associated with decreased delinquent behavior and changes in family relations mediated the relationship between caregiver-rated adherence and reductions in delinquent behavior.
Abstract: The mechanisms through which multisystemic therapy (MST) decreased delinquent behavior were assessed in 2 samples of juvenile offenders. Sample 1 included serious offenders who were predominantly rural, male, and African American. Sample 2 included substance-abusing offenders who were predominantly urban, male, and Caucasian. Therapist adherence to the MST protocol (based on multiple respondents) was associated with improved family relations (family cohesion, family functioning, and parent monitoring) and decreased delinquent peer affiliation, which, in turn, were associated with decreased delinquent behavior. Furthermore, changes in family relations and delinquent peer affiliation mediated the relationship between caregiver-rated adherence and reductions in delinquent behavior. The findings highlight the importance of identifying central change mechanisms in determining how complex treatments such as MST contribute to ultimate outcomes.

Journal ArticleDOI
01 Mar 2000-Blood
TL;DR: The study establishes that the maturation/morphogenesis of blood vessels can be defined in terms of a sequential pattern of expression in which TAL1 and Flk1 are expressed first followed by PECAM, CD34, VE-cadherin, and later Tie2; and Tal1 expression is down-regulated in endothelial cells of mature vessels.

Journal ArticleDOI
TL;DR: Vagus nerve stimulation appears to be a promising new somatic intervention that may improve the understanding of brain function and has promise in the treatment of neuropsychiatric disorders.

Journal ArticleDOI
TL;DR: Daily left prefrontal TMS for 2 weeks significantly reduced depression symptoms greater than did sham and active TMS subjects had significantly greater improvement on the Beck Depression Inventory as well as the Hamilton Anxiety Rating Scale.

Journal ArticleDOI
TL;DR: Delayed disclosure of childhood rape was very common, and long delays were typical, which suggests that the likelihood of disclosure in a given case is difficult to estimate, and predictions based on single variables are unwarranted.

Journal ArticleDOI
01 Apr 2000-Cancer
TL;DR: Desmoid tumors (aggressive fibromatoses) are benign neoplasms with high rates of recurrence after surgery, and Radiotherapy is sometimes reported to prevent recurrences, but not in all studies.
Abstract: BACKGROUND Desmoid tumors (aggressive fibromatoses) are benign neoplasms with high rates of recurrence after surgery. Radiotherapy is sometimes reported to prevent recurrences, but not in all studies. In order to evaluate the effect of radiation, comparative analysis was performed. METHODS The authors conducted a MEDLINE search and collected all articles in the English language on the treatment of “desmoid tumor” or “aggressive fibromatosis” from the years 1983–1998. They categorized treatment into three groups: surgery alone (S), surgery with radiotherapy (S + RT), or radiotherapy alone (RT). The S and S + RT groups were each subdivided according to whether margins were free (−), positive (+), or unknown. Each subgroup was divided into cases with primary, recurrent, or unknown tumor. RESULTS The local control rates after treatment for cases in the S group with (−) margins, (+) margins, and overall were 72%, 41%, and 61%, respectively. For the S + RT group the local control results were 94%, 75%, and 75%, respectively, significantly different when compared with the results for the S group. For the RT group, the local control was 78%, significantly superior to that of the S group (61%). Cases with primary and recurrent tumors had significantly superior local control rates with S + RT or RT versus S. Radiotherapy complications noted were fibrosis, paresthesias, edema, and fracture. CONCLUSIONS RT or S + RT results in significantly better local control than S. Even after dividing the groups into cases with free and positive margins and cases with primary and recurrent tumors, the best local control is achieved with RT or S + RT. Cancer 2000;88:1517–23. © 2000 American Cancer Society.

Journal ArticleDOI
TL;DR: In this article, the authors describe the distribution of pelvic organ support stages in a population of women seen at outpatient gynecology clinics for routine gynecologic health care, and evaluate the stages of support by variable for trends with Pearson χ 2 statistics.

Journal ArticleDOI
TL;DR: The results demonstrate the fulfillment of the genetic equivalent of Koch's postulate, where susceptibility loci in a lupus-prone strain are identified by a genome scan, isolated and functionally characterized by congenic dissection, and finally shown to mediate full disease expression when recombined in a normal genome.
Abstract: We previously produced three congenic strains carrying lupus susceptibility genes (Sle1-Sle3) from the lupus-prone NZM2410 mouse on the C57BL/6 background and characterized their component phenotypes. Sle1 mediates the loss of tolerance to nuclear antigens; Sle2 lowers the activation threshold of B cells; and Sle3 mediates a dysregulation of CD4+ T cells. We have now created a collection of bi- and tricongenic strains with these intervals and assessed the autoimmune phenotypes they elicit in various combinations. Our results indicate that Sle1 is key for the development of fatal lupus. The combination of Sle1 with Sle2, Sle3, or the BXSB-derived autoimmune accelerating gene yaa results in the development of systemic autoimmunity with variably penetrant severe glomerulonephritis culminating in kidney failure. In contrast, two locus combinations of Sle2, Sle3, and yaa failed to mediate fatal disease. These results indicate that the loss of tolerance to chromatin mediated by Sle1 is essential for disease pathogenesis and identify the pathway occupied by Sle1 as a strategic target for therapeutic intervention in systemic lupus erythematosus. The coexpression of Sle1, Sle2, and Sle3 as a B6-triple congenic results in severe systemic autoimmunity and fully penetrant, fatal glomerulonephritis. These results demonstrate the fulfillment of the genetic equivalent of Koch's postulate, where susceptibility loci in a lupus-prone strain have been identified by a genome scan, isolated and functionally characterized by congenic dissection, and finally shown to mediate full disease expression when recombined in a normal genome.

Journal ArticleDOI
18 Dec 2000-Oncogene
TL;DR: Through definition of authentic target genes, this work will begin to understand the mechanisms by which Ets factors control normal and abnormal cellular processes.
Abstract: Ets is a family of transcription factors present in species ranging from sponges to human. All family members contain an approximately 85 amino acid DNA binding domain, designated the Ets domain. Ets proteins bind to specific purine-rich DNA sequences with a core motif of GGAA/T, and transcriptionally regulate a number of viral and cellular genes. Thus, Ets proteins are an important family of transcription factors that control the expression of genes that are critical for several biological processes, including cellular proliferation, differentiation, development, transformation, and apoptosis. Here, we tabulate genes that are regulated by Ets factors and describe past, present and future strategies for the identification and validation of Ets target genes. Through definition of authentic target genes, we will begin to understand the mechanisms by which Ets factors control normal and abnormal cellular processes.

Journal ArticleDOI
TL;DR: Since low birth weight increases the risk of ESRD from multiple causes, the data suggest that an adverse environment in utero impairs kidney development and makes it more vulnerable to damage from a range of pathological processes.
Abstract: Background The southeastern United States is a region in which rates of cardiovascular and renal diseases are excessive. Within the Southeast, South Carolina has unusually high rates of end-stage renal disease (ESRD) in young people, with more than 70% of cases attributed to hypertension and diabetes. Objective To determine whether the increased vulnerability to early-onset ESRD might originate through impaired renal development in utero as measured by low birth weight. Methods Patients who were diagnosed with renal failure and undergoing dialysis from 1991 through 1996 were identified from the ESRD registry maintained by the Southeastern Kidney Council, Raleigh, NC. Birth weights reported on birth certificates were selected for the ESRD cases and non-ESRD controls who were born in South Carolina in 1950 and later. Birth weights were compared for 1230 cases and 2460 controls who were matched for age, sex, and race. Results Low birth weight was associated with ESRD among men and women as well as blacks and whites. Among people whose birth weight was less than 2.5 kg, the odds ratio for ESRD was 1.4 (95% confidence interval, 1.1-1.8) compared with people who weighed 3 to 3.5 kg. This association was present for renal failure resulting from diabetes, hypertension, and other causes. Conclusions Low birth weights, which reflect adverse effects on development in utero, contribute to the early onset of ESRD in South Carolina. Since low birth weight increases the risk of ESRD from multiple causes, the data suggest that an adverse environment in utero impairs kidney development and makes it more vulnerable to damage from a range of pathological processes.

Journal ArticleDOI
18 Dec 2000-Oncogene
TL;DR: A brief survey of what is known to date about how this family of transcription factors is regulated by cellular signaling with a special focus on Ras responsive elements (RREs), the MAP kinases (Erks, p38 and JNK) and Ca2+-specific pathways is provided and a description of the multiple roles of Ets family members in the lymphoid system is included.
Abstract: Cellular responses to environmental stimuli are controlled by a series of signaling cascades that transduce extracellular signals from ligand-activated cell surface receptors to the nucleus. Although most pathways were initially thought to be linear, it has become apparent that there is a dynamic interplay between signaling pathways that result in the complex pattern of cell-type specific responses required for proliferation, differentiation and survival. One group of nuclear effectors of these signaling pathways are the Ets family of transcription factors, directing cytoplasmic signals to the control of gene expression. This family is defined by a highly conserved DNA binding domain that binds the core consensus sequence GGAA/T. Signaling pathways such as the MAP kinases, Erk1 and 2, p38 and JNK, the PI3 kinases and Ca2+-specific signals activated by growth factors or cellular stresses, converge on the Ets family of factors, controlling their activity, protein partnerships and specification of downstream target genes. Interestingly, Ets family members can act as both upstream and downstream effectors of signaling pathways. As downstream effectors their activities are directly controlled by specific phosphorylations, resulting in their ability to activate or repress specific target genes. As upstream effectors they are responsible for the spacial and temporal expression or numerous growth factor receptors. This review provides a brief survey of what is known to date about how this family of transcription factors is regulated by cellular signaling with a special focus on Ras responsive elements (RREs), the MAP kinases (Erks, p38 and JNK) and Ca2+-specific pathways and includes a description of the multiple roles of Ets family members in the lymphoid system. Finally, we will discuss other potential mechanisms and pathways involved in the regulation of this important family of transcription factors.

Journal ArticleDOI
TL;DR: Temperature, pH, availability of naturally occurring or of supplemented carbon sources, and the presence or absence of H(2) or other electron donors and competing electron acceptors influence the de chlorination rate, extent and route of PCB dechlorination.