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Biomedical subjects

G Anderson

Publications and source records attributed to G Anderson.

At least 19 recordsLinked to original sources
PubMed1995

Protecting children with chronic illness in a competitive marketplace.

Health care for children with chronic illnesses is significantly more expensive than for the average child. Children with chronic illnesses are especially vulnerable in a competitive health care environment because of the higher ongoing cost associated with treating their illnesses and the inherent pressures to reduce services to manage within the capitated rate. To minimize the adverse impact a competitive market could have on these children, a "carve-out" for specific medical conditions is discussed. A capitation pricing system that reflects their higher costs is proposed, as well as a delivery system that is focused on their needs.

Capitation Fee↗
PubMed1995

Positive selection of thymocytes involves sustained interactions with the thymic microenvironment.

CD4+8+ cortical thymocytes are critically dependent upon interaction with the thymic epithelium to undergo positive selection and maturation into single-positive CD4+ or CD8+ cells. Here we investigate further the nature of this interaction and provide evidence that positive selection requires sustained, rather than "single hit," interaction with thymic stromal cells. We also show that calcineurin-mediated signaling in thymocytes is required for the initial stages of positive selection, but is not essential throughout the period of thymocyte dependence on stromal cell contact during positive selection. In addition, we show that double-positive thymocytes that have initiated positive selection (CD69+4+8+) and newly generated single-positive (CD69+4+) cells differ markedly in response to the same stimulus through the TCR. The former undergo deletion, whereas the latter proliferate, indicating that a critical change in response to TCR ligation occurs within the narrow developmental window between these two stages.

Animals↗
PubMed1995

Stimulation of thymocytes before and after positive selection results in the induction of different NF-kappa B/Rel protein complexes.

Positive selection triggers the differentiation of immature CD4+8+TCRlow thymocytes into TCRhigh single-positive CD4+ or CD8+ cells and is associated with major changes in gene expression. However, little is known about the DNA binding factors controlling these fundamental changes. Here we have examined NF-kappa B/Rel subunit expression and DNA-binding activity in developing thymocytes before and after the induction of positive selection. We show that positive selection is accompanied by the strong up-regulation of c-rel mRNA expression and the constitutive activation of p50/p65 and p50/c-Rel NF-kappa B/Rel complexes, confirming the activation-like status of cells undergoing positive selection. Moreover, CD69+ cells that have initiated positive selection (but not their preselection CD4+8+TCR- precursors) respond to stimulation by the preferential activation of c-Rel-containing DNA-binding complexes. Because the different NF-kappa B/Rel dimers have distinct transcriptional activities and binding site preferences, this preferential activation of c-Rel-containing DNA-binding complexes may well have implications for the changes in gene expression and functional response associated with positive selection.

Amino Acid Sequence↗
PubMed1995

A retrospective analysis of the long-term effect of splenectomy on late infections, graft-versus-host disease, relapse, and survival after allogeneic marrow transplantation for chronic myelogenous leukemia.

The present study was performed as a retrospective analysis of the role of pretransplant splenectomy to determine the incidence of late bacterial infections, acute and chronic graft-versus-host disease (GVHD), relapse, and survival among 358 patients receiving HLA-identical marrow grafts for chronic myelogenous leukemia. Sixty-eight (19%) of the 358 patients had undergone splenectomy before transplantation. There was a trend towards more grade II-IV acute GVHD among splenectomized patients, but this was not significant in the multivariate analysis. The incidence of chronic GVHD was similar for splenectomized and nonsplenectomized patients. Late infectious complications did not significantly differ between splenectomized and control patients (rates per patient year were 0.16 and 0.14, respectively). The overall risk of leukemic relapse was significantly increased for splenectomized patients (56% v 32% for controls, P = .001) and control patients with splenomegaly (P < .0001). Splenectomy and splenomegaly remained significant and independent hazards for relapse in the multivariate analysis (hazard ratio [HR], 1.82, P = .029; and HR, 1.49, P = .002; respectively). Relapse was also increased in patients with advanced disease (HR, 2.95; P = .0001), in patients with T-cell-depleted marrow (HR, 4.51; P = .0001), and in the female donor and male recipient combination (HR, 1.74; P = .044). Patients with splenectomy had an increased overall mortality (HR, 1.18), but this was not statistically significant in the multivariate analysis. In summary, our study showed no significant influence of splenectomy on late posttransplant infections, acute or chronic GVHD, or overall survival. There was no evidence that splenectomy decreased recurrence of chronic myelogenous leukemia.

Abscess↗
PubMed1995

Intracellular signaling events during positive and negative selection of CD4+CD8+ thymocytes in vitro.

We have used in vitro models of thymocyte positive and negative selection in conjunction with selective inhibitors of the TCR-mediated signaling cascade to investigate the intracellular signaling events that mediate these processes. We report that Ro 31.8425, a potent and selective inhibitor of protein kinase C, which blocks the activation of mature T cells in a dose-dependent fashion, has no effect on either positive or negative selection of CD4+8+ thymocytes. In contrast, cyclosporin A fails to prevent negative selection, but inhibits positive selection through a direct effect on developing thymocytes, rather than through the perturbation of stromal cell support. Thus, our data suggest that positive and negative selection may operate via distinct intracellular signaling pathways.

Animals↗
PubMed1995

Linkage between brain serotonin concentration and the sex-specific part of the Y-chromosome in mice.

The implication of the sex-specific part of the Y-chromosome (YS-SP) on brain serotonin (5-HT) level was investigated using congenic strains for this chromosomal region. The 5-HT level, which was higher in the NZB than in the CBA/H strain of mice, was depleted by the transfer of the YS-SP from NZB on CBA/H whereas the transfer of the YS-SP from CBA/H on NZB had no effect. The variations of 5-HT levels were not correlated with plasma testosterone concentration which is also dependent of the YS-SP.

Animals↗
PubMed1995

A decrease from 8 to 6 weeks in obstetrics and gynecology clerkship: effect on medical students' cognitive knowledge.

We undertook this study to determine whether a decrease in the amount of time a third-year medical student spent in an obstetrics and gynecology clerkship would cause a decrease in the knowledge of the subject. We compared National Board of Medical Examiners (NBME) obstetrics and gynecology subject examination scores of 168 students at the University of Texas Medical Branch at Galveston completing an 8-week obstetrics and gynecology rotation or the 1989-1990 academic year to scores of 187 University of Texas Medical Branch students competing a 6-week rotation during 1990-1991. No significant change in the total mean NBME subject examination score in obstetrics and gynecology was noted after the decrease in rotation length. Passing scores were those greater than 445 points. The failure rate for those students who completed the 8-week rotation was consistent throughout the 1989-1990 academic year. In contrast, those students who rotated through obstetrics and gynecology during the 6-week clerkship in the first half of the academic year had a failure rate that was statistically higher than those taking the clerkship in the last half of the year. The length of the obstetrics and gynecology clerkship was shortened to 6 weeks without significantly affecting students' overall performance on the NBME obstetrics and gynecology subject examination. However, a greater percentage of students who completed the rotation during the first half of the year scored low on the NBME obstetrics and gynecology subject examination than did those taking the rotation and thus the NBME subject examination in the second half of the year.

Clinical Clerkship↗
PubMed1995

The role of the thymus during T-lymphocyte development in vitro.

To date, fetal thymic organ culture is the only in-vitro system capable of supporting a complete programme of T-lymphocyte development in a manner comparable to that seen in vivo. In this review, we will summarise recent studies in which thymic organ cultures have been used to investigate the regulatory mechanisms of particular stages of thymocyte development. In addition, the use of other culture systems of T-cell maturation will be discussed in an attempt to define the optimal conditions for T-cell development in vitro.

Animals↗
PubMed1995

Exfoliative cytology and electron microscopy in the diagnosis of hairy leukoplakia.

The diagnosis of lesions clinically suggestive of hairy leukoplakia was assessed by light and electron microscopic examination of cytologic smears. We found exfoliative cytology to be a simple and noninvasive technique that can confirm the clinical diagnosis of hairy leukoplakia. Our results suggest that electron microscopy may be more sensitive and reliable than light microscopy in confirming the clinical diagnosis of hairy leukoplakia.

AIDS-Related Opportunistic Infections↗
PubMed1995

Arteriole constriction following ischemia in denervated skeletal muscle.

Arteriolar diameters and flow patterns were determined in the isolated rat cremaster muscle following 4 hr of total ischemia. Two groups of six rats each were studied--an innervated group and a denervated group. The microcirculation was observed using intravital microscopy, and the images were recorded on videotape. The whole arterial tree was scanned, and the smallest vessel diameter for each arterial segment was measured. Preischemic mean arteriole diameters were significantly larger in the denervated group, compared to the innervated group. Following ischemia, during the 3 hr of reperfusion, the main (AI) cremaster arteriole from both the innervated and denervated groups constricted to 50 to 70 percent of pre-ischemic diameters. However, the actual diameters (as distinct from percentage change) were not significantly different between the innervated and denervated groups. There were significant differences in flow patterns. Some A2 and A3 vessels became temporarily nonflowing vessels (either open but without low, or closed by severe spasm). These poorly-functioning vessels were significantly more common in the denervated group. Furthermore, this phenomenon of temporary no-flow persisted longer in the denervated group over the 3-hr reperfusion period. These observations suggest that the ability to recover quickly from an ischemic insult is less in tissues that have been denervated.

Animals↗
PubMed1995

A randomized clinical trial of intraoral soft splints and palliative treatment for masticatory muscle pain.

Thirty subjects seeking treatment for masticatory muscle pain at a university-based TMJ clinic were randomly assigned to soft-splint, palliative-treatment, and no-treatment groups. After 4 to 11 weeks of treatment, subjects were evaluated for changes from their baseline levels of symptoms, maximum pain-free opening, pain thresholds measured by a pressure algometer, and occlusal contacts. With the use of the multivariate analysis of variance and analysis of covariance, the results suggest that the soft-splint group had statistically significant improvement (P < .01), the palliative-treatment group had improvement that was not statistically significant, and the no-treatment group had a slight aggravation of symptoms. The soft-splint group had fewer occlusal contact changes assessed with shimstock compared to the palliative-treatment and no-treatment groups. The findings of this study suggest that the soft splint is an effective short-term treatment for reducing the signs and symptoms of masticatory muscle pain in patients, and the soft splint does not cause occlusal changes.

Adolescent↗
PubMed1994

Characteristics of an in vitro system of thymocyte positive selection.

We investigated the phenotypic changes accompanying maturation of CD4+CD8+ thymocytes in the presence of thymic stomal cells in vitro. Many of the features that are characteristic of positive selection in vivo, such as an ordered down-regulation of CD4 or CD8 together with up-regulation of the TCR-alpha beta complex, also occurred in vitro. Transient expression of CD69 was also observed, together with activation of IL-2 and IL-4 cytokine genes, providing further evidence that positive selection in vitro involves a pattern of gene regulation comparable to that seen in vivo.

Animals↗
PubMed1994

Enhanced stress responsivity of Tourette syndrome patients undergoing lumbar puncture.

Tourette's syndrome (TS) is a complex inherited neuropsychiatric disorder that is characterized by multiple motor and phonic tics. Stress-related fluctuations in symptom severity and medication responsiveness are common, and patients often report that tics are worsened by fatigue, emotional trauma, and anxiety. We examined the effects of lumbar puncture (LP) stress on plasma adrenocorticotropin (ACTH) and cortisol, urinary catecholamines, and self- and clinician ratings of anxiety in 13 medication-free TS patients and 10 normal controls, ages 17 to 41 years. The TS patients secreted significantly more ACTH than the normal controls in response to the stress of the lumbar puncture. Compared to the controls the TS patients had significantly greater postLP mean and postLP peak ACTH levels. The TS patients also excreted significantly more norepinephrine in the 20 hr preceding the lumbar puncture and reported higher levels of anxiety before and during the procedure than the controls. In addition, urinary norepinephrine excretion of the TS patients was significantly correlated with clinician ratings of tic severity. The results were not related to current levels of depression and anxiety. Taken together, these findings suggest that a subset of TS patients may be characterized by heightened reactivity of the hypothalamic-pituitary-adrenal axis and related noradrenergic sympathetic systems.

Adrenocorticotropic Hormone↗
PubMed1994

Thymic epithelial cells provide unique signals for positive selection of CD4+CD8+ thymocytes in vitro.

Using a novel system that supports positive selection in vitro, we have investigated the cellular requirements for this process by testing the ability of individual thymic and nonthymic stromal cell types to support the maturation of CD4+CD8+ thymocytes into CD4+ or CD8+ T cells. We show that thymic cortical epithelial cells are unique in their ability to mediate this maturation, and suggest that in addition to TCR ligation, these cells supply specific signals for positive selection. Moreover, by demonstrating positive selection on ECDI (1-ethyl-3-[3'dimethyl-aminopropyl]-carbodiimide)-fixed epithelial cells in this system, we provide direct evidence that the provision of these signals involves interactions with epithelial cell surface molecules rather than the release of soluble factors.

Animals↗