Showing papers by "Medical University of South Carolina published in 1989"

Considerations in measurement of marginal fit

Abstract: The terminology describing "fit" and the techniques used for measuring fit vary considerably in the literature. Although fit can be most easily defined in terms of "misfit," there are many different locations between a tooth and a restoration where the measurements can be made. In this work, the measurements of misfit at different locations are geometrically related to each other and defined as internal gap, marginal gap, vertical marginal discrepancy, horizontal marginal discrepancy, overextended margin, underextended margin, absolute marginal discrepancy, and seating discrepancy. The significance and difference in magnitude of different locations are presented. The best alternative is perhaps the absolute marginal discrepancy, which would always be the largest measurement of error at the margin and would reflect the total misfit at that point.

Polyethylene glycol-conjugated superoxide dismutase and catalase reduce ischemic brain injury

Abstract: Superoxide dismutase and catalase enzymatically scavenge superoxide and hydrogen peroxide, respectively. Conjugation of polyethylene glycol to superoxide dismutase (PEG-SOD) or catalase (PEG-CAT) prolongs the circulatory half-life of the native enzymes and enhances their intracellular access. We studied the protective effect of these free radical scavengers on ischemic brain injury using a rat model of focal cerebral ischemia, which is suitable for therapeutic trials. Intravenous administration of PEG-SOD (10,000 U/kg) and PEG-CAT (10,000 U/kg) before ischemia reduced the infarct volume (treatment, 139 +/- 9 mm3, means +/- SE, N = 38; placebo, 182 +/- 8 mm3, n = 37, P less than 0.002). This finding supports the concept that superoxide and hydrogen peroxide contribute to brain injury following focal cerebral ischemia.

Benign familial neonatal convulsions linked to genetic markers on chromosome 20

Abstract: Recurrent seizures, commonly known as epilepsies, occur in 1.7% of the general population by age 401. The factors that initiate or underlie seizures are not well understood, but trauma, infectious disease and genetics have been implicated. An understanding of the molecular basis of seizures would shed light on the basic mechanisms of neuronal homeostasis and allow new therapeutic strategies to be explored. Here, we report the mapping of an epilepsy gene to a specific chromosomal region, on the basis of cosegregation of two closely-linked DNA markers with a form of epilepsy known as benign familial neonatal convulsions (BFNC2, £12120 in ref. 3). The linked markers confirm the genetic basis and autosomal dominant inheritance of this trait, and localize the gene causing BFNC in this family to the long arm of chromosome 20. This regional placement is the first step towards the isolation of a gene involved in neuronal activity in the human brain.

Polymerase chain reaction amplification products separated on rehydratable polyacrylamide gels and stained with silver

Abstract: Separation of polymerase chain reaction (PCR) amplification of specific fragment length polymorphisms was carried out on rehydratable polyacrylamide gels on a horizontal flat slab system. A discontinuous sulfate-borate buffer system was employed on 5-8% T gels crosslinked with 3.5% C. Samples were diluted in leading sulfate ion buffer at 1/10 the ionic strength of the separating gel buffer and placed directly onto the surface of the rehydrated gels in 0.5-10 microliters volumes. The trailing ion and counterion were contained in a gel plug and placed directly onto the anodal and cathodal ends of the gel, and the electrodes placed directly onto the surface of the gel plugs. Filter paper wicks, soaked in diluted leading ion buffer, were placed along each side to lower the ionic strength of the edges, thereby increasing mobility at the edge and thus preventing smile effects. The gel-gel contact of the plug and separating gel prevent the production of a junction potential which occurs between dissimilar materials such as a paper wick and the gel. Ten- to 20-cm separations were carried out from 2-5 h, respectively, and resolution in the 20 cm system was 1.6-4 bp (base pairs) between 100 and 500 bp, 4-7 bp between 500 and 1000 bp, 12-20 bp between 1000 and 2000 bp and about 50 bp between 2000 and 3000 bp. Between 3000 and 4000 bp, resolution fell off to +/- 100 bp. Sensitivity, using a silver stain, indicated that one could readily distinguish less than 10 pg of DNA per mm width on the gels.(ABSTRACT TRUNCATED AT 250 WORDS)

Thromboxane, prostaglandin and leukotriene receptors.

Abstract: Thromboxanes (TX), prostaglandins (PG), and leukotrienes (LT) (eicosa­ noids) are metabolites of the the 20-carbon fatty acid arachidonic acid. Current evidence supports potential pathophysiologic roles for these autocoids in many diseases (1-3). While the synthesis and metabolism ofthese auto­ coids have been studied extensively in normal and pathologic states, the study of their receptors has lagged far behind. With the development of drugs that will be targeted to these receptors, there is a pressing need to improve our understanding of the fundamental characteristics of these important receptors.

Role of cardiovascular risk factors in prevention and treatment of macrovascular disease in diabetes

Abstract: D iabetes mellitus is a major risk factor for morbidity and mortality due to coronary heart disease, cerebrovascular disease, and peripheral vascular disease in the United States. The prevalence of these macrovascular complications is increased about twoto fourfold in diabetic populations. In 1987, these macrovascular complications accounted for most of the hospitalizations for diabetes and contributed substantially to the 20.4 billion dollars spent for diabetes care in the United States. Multiple risk factors for macrovascular disease are frequently found in individuals with diabetes. There is an increased prevalence of hypertension and lipid abnormalities in many populations with diabetes. Many individuals with diabetes have not stopped smoking despite evidence that this is a major cardiovascular risk factor. There are other factors that may be associated with macrovascular disease in diabetes, including obesity, impaired glucose tolerance (IGT), hyperglycemia, hyperinsulinemia, microalbuminuria, elevated fibrinogen levels, altered platelet function, and qualitative lipoprotein abnormalities. Primary and secondary intervention trials directed at cardiovascular risk factors in nondiabetic individuals have been performed and data are now available. Advances have also occurred in nutritional management, exercise programs, behavioral approaches, and pharmacological therapy for diabetes and its major risk factors, and advances have been made in our understanding of atherogenesis. These developments led the American Diabetes Association (ADA) to convene a consensus development conference, on 10-12 May 1989, on the role of cardiovascular risk factors in the prevention and treatment of macrovascular disease in diabetes. The conference consisted of 19 invited presentations and considerable discussion from a large audience of health-care professionals. A consensus panel with expertise in clinical diabetes, clinical investigation, epidemiology, nutrition, cardiovascular diseases (CVD), and lipid and lipoprotein disorders considered a broad spectrum of issues concerned with macrovascular disease in diabetes. The panel reached a consensus on answers to the following questions:

Distribution of immunoreactive Na+,K+-ATPase in gerbil cochlea.

Abstract: The distribution of Na+,K+-ATPase was mapped in cochleas of mature gerbils with normal hearing, using a specific and sensitive immunocytochemical method. Na+,K+-ATPase was abundant in the basolateral plasma membrane of marginal cells in the stria vascularis. Considerable levels of enzyme were also associated with the surfaces of spiral ganglion neurons and their central and peripheral processes. An unexpected finding was the detection of high levels of immunoreactive Na+,K+-ATPase in three different populations of cells lying in the inferior portion of the spiral ligament and at the medial and lateral border of the scala vestibuli just superior to the attachment of Reissner's membrane. Cells in these areas shared the morphological characteristics of cells specialized for active transport but appeared to be nonpolarized, suggesting a uniform distribution of Na+,K+-ATPase over their entire plasmalemma. The presence of these three distinct cell populations in the cochlea of several mammalian species suggests that they play an important role in cochlear function, perhaps that of regulating the cation content of perilymph. The absence of discrete concentrations of Na+,K+-ATPase-rich cells in the perilymphatic connective tissue of the bird cochlea and the mammalian vestibular system suggests further that these cells may be involved with generating and maintaining the high endolymphatic potential unique to the mammalian cochlea.

Load regulation of the properties of adult feline cardiocytes: growth induction by cellular deformation.

Abstract: Previous studies from this laboratory have demonstrated rapid and reversible changes in cardiac structure, composition, and function in response to load alterations in vivo. The purpose of the present in vitro study was to examine directly in the isolated, quiescent adult cardiocyte the potential growth-regulating effects of load changes through the use of an extremely simple and well-defined cell culture preparation. Freshly isolated cardiocytes were plated onto a deformable, laminin-coated substrate and maintained in serum-free culture medium for 3 days. On the third day in culture, the resting length of these quiescent cardiocytes, and thus their external load, was increased by linear deformation of the substrate to which these cells were firmly adhered. Cardiocyte loading resulted in increases of approximately 10% in cell length, approximately 8% in cell surface area, and approximately 7% in sarcomere length. Three markers of increased synthetic activity were then examined: 1) [3H]uridine incorporation into nuclear RNA, 2) [3H]phenylalanine incorporation into cytoplasmic protein, and 3) [3H]thymidine incorporation into DNA. Cardiocyte loading resulted in mean increases of 186% in nuclear RNA labeling and 89% in cytoplasmic protein labeling. The finding that the increase in [3H]phenylalanine incorporation could be blocked readily by cycloheximide showed that the increase in cytoplasmic labeling in response to cardiocyte loading was not simply the result of increased amino acid transport but instead resulted from the incorporation of label into newly synthesized protein. An absence of [3H]thymidine nuclear incorporation in the loaded cardiocytes indicated that DNA synthesis was not activated in these cells. These data constitute the initial demonstration that an increase in load is at least a sufficient stimulus for the induction of increased RNA and protein synthetic activity in the adult mammalian cardiocyte. This evidence for the role of load as an independent regulator of cardiac growth in the adult suggests that hemodynamic changes may lead directly to appropriate alterations in cardiac structure and composition through the transduction of this physical stimulus into one or more biochemical signals that modulate gene expression.

Erysipelothrix rhusiopathiae: an occupational pathogen.

Abstract: Erysipelothrix rhusiopathiae is a nonsporulating, gram-positive, rod-shaped bacterium which was identified more than 100 years ago as the etiologic agent of swine erysipelas. Since then, it has been found to cause infection in several dozen species of mammals and other animals. Humans become infected through exposure to infected or contaminated animals or animal products. By far the most common type of human infection is a localized, self-limited cutaneous lesion, erysipeloid. Diffuse cutaneous and systemic infections occur rarely. Approximately 50 cases of endocarditis have been reported; all but one recent case have involved native valves. The organism may be isolated from biopsy or blood specimens on standard culture media. It is identified by morphology, lack of motility, and biochemical characteristics; identification may be confirmed by the mouse protection test. It is susceptible to penicillins, cephalosporins, erythromycin, and clindamycin, but it is often resistant to many other antibiotics, including vancomycin, a drug frequently used in empiric therapy for infections due to gram-positive bacteria.

A strategy for determining the pathogenesis of systemic sclerosis. Is transforming growth factor beta the answer

Abstract: Summary and criticism of data implicating cell types, receptor-ligand systems, and tumor necrosis factor, considered relevant to the vascular intimal proliferation, the microvascular obliteration, and the interstitial fibrosis that characterize systemic sclerosis

Propranolol's metabolism is determined by both mephenytoin and debrisoquin hydroxylase activities.

Abstract: The relative contributions of the debrisoquin and mephenytoin isozymes of hepatic cytochrome P-450 to the stereoselective metabolism of propranolol have been studied in a panel of volunteers of known oxidative phenotypes. Six subjects were extensive metabolizers of both debrisoquin and mephenytoin (EM). Four subjects were poor metabolizers of debrisoquin but rapid for mephenytoin (PMD). Five subjects were poor metabolizers of mephenytoin but rapid for debrisoquin (PMM), and one individual had a deficiency for both test compounds (PMD/M). Partial metabolic clearances of each propranolol enantiomer to 4-hydroxypropranolol (4-OH-P), the sulfate, and glucuronide conjugates of 4-OH-P, naphthoxylactic acid (NLA) and propranolol glucuronide, were estimated after a single oral dose of racemic propranolol (80 mg). The partial metabolic clearance of both enantiomers to total 4-OH-P in the PMD group was 75% less than in the EM and PMM groups, indicating the contribution of the debrisoquin isozyme to this route of metabolism. The R/S ratios for the clearance to 4-OH-P were similar between EM and PMD (2.5 +/- 0.5 vs 2.5 +/- 0.4, respectively), implying that the different enzymes involved in ring hydroxylation (i.e., the debrisoquin isozyme and other hydroxylases) have similar stereoselective preferences. The partial metabolic clearance to NLA was 55% less in the PMM group than in the EM and PMD groups, indicating that S-mephenytoin 4-hydroxylase contributes to the metabolic conversion of propranolol to NLA. The R/S ratios for the clearance to NLA were close to unity in all groups. The partial metabolic clearance to propranolol glucuronide also did not exhibit stereoselectivity and was similar in all groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Double-blind controlled trial comparing carbamazepine to oxazepam treatment of alcohol withdrawal.

Abstract: Of 86 alcoholic men with severe alcohol withdrawal who began a double-blind controlled study comparing carbamazepine, 800 mg/day, to oxazepam, 120 mg/day, 66 (carbamazepine, N = 32; oxazepam, N = 34) completed the 7-day trial. In general, the drugs were found to be equally efficacious in treating the withdrawal syndrome and not significantly different with respect to side effects. The subjects taking oxazepam had an increase in global psychological distress from day 3 to day 7, and those taking carbamazepine exhibited a decline. The study suggests that carbamazepine is as effective and safe as benzodiazepine treatment for alcohol withdrawal.

The effects of muscle-building exercise on bone mineral density of the radius, spine, and hip in young men.

Abstract: We previously demonstrated that muscle-building exercise is associated with increases in serum Gla-protein, serum 1,25(OH)2D, and urinary cyclic AMP. These studies were interpreted to mean that this form of exercise increases bone formation and modifies the vitamin D-endocrine system to provide more calcium for bone. The present investigation was carried out in normal young adult white men to determine the effects of exercise on bone mineral density at weight-bearing and nonweight-bearing sites. Twelve men who had regularly engaged in muscle-building exercises (use of weights, exercise machines, or both) for at least 1 year and 50 age-matched controls (aged 19-40 years) were studied. The body weights of the two groups were not different from each other (78 +/- 2 vs. 74 +/- 1 kg, NS). Bone mineral density (BMD) of the lumbar spine, trochanter, and femoral neck was measured by dual-photon absorptiometry, and BMD of the midradius was measured by single photon absorptiometry. It was found that muscle-building exercise was associated with increased BMD at the lumbar spine (1.35 +/- 0.03 vs. 1.22 +/- 0.02 g/cm2, P less than 0.01), trochanter (0.99 +/- 0.04 vs. 0.86 +/- 0.02 g/cm2, P less than 0.01), and femoral neck (1.18 +/- 0.03 vs. 1.02 +/- 0.02 g/cm2, P less than 0.001) but not at the midradius (0.77 +/- 0.02 vs. 0.77 +/- 0.01 g/cm2, NS). These studies provide additional evidence that muscle-building exercise is associated with increases in BMD at weight-bearing sites but not at nonweight-bearing sites.

Prevalence of scleroderma spectrum disorders in the general population of South Carolina.

Abstract: The prevalence of scleroderma spectrum disorders (including systemic sclerosis [SSc] meeting the American Rheumatism Association criteria and the less typical disorders meeting only our study criteria) was determined in a random sample of 6,998 subjects from the general population of South Carolina. The results suggest that the prevalence of these disorders may range from 67 to 265 per 100,000, which is 4.9 to 19.2 times higher than previously reported for definite SSc. The ratio of nondefinite cases to definite cases of SSc (those meeting American Rheumatism Association criteria) was 2.5. Most of the nondefinite cases were unrecognized prior to our study, which suggests the need for improved early diagnosis of scleroderma spectrum disorders. Brief histories of the 7 patients with scleroderma spectrum disorders whose cases formed the basis for our calculation of prevalence rates are included in this report.

EGF and TGF-alpha are potent chemoattractants for endothelial cells and EGF-like peptides are present at sites of tissue regeneration.

Abstract: We report here that epidermal growth factor (EGF) isolated from male mouse salivary glands is active as a potent chemoattractant for a rat heart vascular endothelial cell line (RHEC). Human EGF and transforming growth factor-alpha (TGF-alpha) produced in Escherichia coli are also active as chemoattractants for these cells. The chemotactic response of the cells is induced by concentrations of murine EGF that ranged from 0.01 to 1.0 nM with similar specific activities for both the human EGF and TGF-alpha. Other growth factors such as fibroblast growth factor (FGF), TGF-beta, platelet-derived growth factor (PDGF), insulin, or IGF were not active as chemoattractants for these cells. The chemotactic response exhibited similar kinetics to those reported for connective tissue cells responding to PDGF (2-6 h) and required both RNA and protein synthesis. However, in contrast to NIH/3T3 cells responding to PDGF, the proliferating cultures of RHEC respond as well as growth-arrested cultures in the chemotaxis assay. In in vivo studies of connective tissue regeneration it appears that EGF-like factors are present in wound fluid collected from rats. Acid extracts of wound fluid contained a RHEC chemotactic activity that was neutralized with anti-EGF antisera. These studies indicate that EGF-like factors may function in vivo to control in part the angiogenic events that occur during tissue repair.

Interleukin-2 in scleroderma: correlation of serum level with extent of skin involvement and disease duration.

Abstract: Study Objective:To assess whether interleukin-2 has a role in the pathogenesis of scleroderma Design:Observe serum effect on the in-vitro growth of an interleukin-2-dependent cytotoxic T-

Effects of branched‐chain amino acids on protein turnover

Abstract: Amino acid availability rapidly regulates protein synthesis and degradation. Increasing amino acid concentrations above the levels found in post-absorptive plasma stimulates protein synthesis in a dose-dependent manner at the level of mRNA translation-initiation and inhibits protein degradation by inhibiting lysosomal autophagy. The anabolic effects of insulin on protein synthesis and protein degradation are exerted at the same sites (i.e., peptide chain initiation and lysosomal stabilization) allowing for a rapid synergistic response when both amino acids and insulin increase after a protein-containing meal. In perfused liver preparations, protein anabolic effects are exerted by a group of amino acids acting in concert. The BCAA are among the amino acids required for stimulation of hepatic protein synthesis, but there is no evidence that BCAA or leucine alone are effective. Leucine alone is an important inhibitor of hepatic protein degradation, but maximal inhibition requires in addition several other regulatory amino acids. In heart and skeletal muscle in vitro, increasing the concentration of the three BCAA or of leucine alone reproduces the effects of increasing the supply of all amino acids in stimulating protein synthesis and inhibiting protein degradation. Skeletal muscle is the largest repository of metabolically active protein and a major contributor to total body nitrogen balance. Supplying energy alone (i.e., carbohydrate and lipids) cannot prevent negative nitrogen balance (net protein catabolism) in animals or humans; only provision of amino acids allows the attainment of nitrogen balance. In rats and in humans nourished parenterally, provision of balanced amino acid solutions or of only the three BCAA cause similar improvements in nitrogen balance for several days. There is some evidence that infusions of leucine alone can stimulate muscle protein synthesis in vivo; the effect may be transitory and was not observed by all investigators; provisions of excess leucine alone does not seem to affect total body or muscle protein degradation in vivo. In postabsorptive rats, in vivo, infusion of the three BCAA together stimulates muscle protein synthesis as much as the infusion of a complete amino acid mixture or of a mixture of essential amino acids; the in vivo effect requires coinfusion of glucose or of small (physiological) doses of insulin, suggesting synergism between insulin and amino acids.(ABSTRACT TRUNCATED AT 400 WORDS)

Collaborative Consultation: Improving Parent-Teacher Communication.

Abstract: The parent-teacher conference is reconceptualized as collaborative consultation with teacher and parent assuming the roles of problem solvers.

Stress Management for Rape Victims

Abstract: Our major objective in this chapter is to describe stress management procedures we have developed to be used with rape victims. We will discuss issues involved in the definition of rape, in the estimation of its incidence, and in the investigation of rape-related problems. We will briefly describe the Sexual Assault Research Project and review our findings and those of others regarding the aftermath of rape. Having substantiated our contention that rape is a stressful event that produces substantial, long-lasting problems for many of its victims, we will review other treatment procedures for rape-induced problems, describe our stress inoculation procedure, present assessment data on victims requesting treatment, discuss preliminary results regarding treatment efficacy, and provide information about the use of stress inoculation training with a victim. The chapter will conclude with some observations and speculations about general treatment issues.

Tissue kallikreins and kinins: regulation and roles in hypertensive and diabetic diseases.

Abstract: The spectrum of cellular, or whole animal responses to kinins has expanded enormously in the last five years. The molecular basis for these consequences of kinin-kinin receptor interactions is being glimpsed as a series of cascading and parallel biochemical events occurring either in the same or adjacent, but communicating, cells of the same tissue (e.g. epithelial, endothelial, muscle, neural). Although it is likely that even more kinin-induced events remain to be discovered, like the interesting effects of the peptides on osteoclastic activity (128), a greater challenge in this field is the gathering of insights into precisely how the regulation of system component gene expression is coordinately carried out to allow component protein synthesis, transport and processing when necessary, and limitation of activities, when required. With these insights, we will be more able to understand the meaning of many observations of tissue kallikrein-kinin system abnormalities in common human diseases. This understanding will then make more obvious the drug design strategies to be used to stimulate or replace, and modulate or inhibit kallikrein-kinin system components in those diseases.

Pathway-selective sex differences in the metabolic clearance of propranolol in human subjects

Abstract: This study determined the total clearance of propranolol and the partial clearances through each of its three primary metabolic pathways after administration of an 80 mg single oral dose in 28 young, white subjects (13 women; 15 men). The oral clearance of propranolol was significantly higher (63%, p less than 0.02) in the men (65.7 +/- 7.7 ml/min/kg; mean +/- SE) than in the women (40.2 +/- 6.2 ml/min/kg). This sex difference was mainly attributable to a 137% higher clearance through the P-450-mediated side-chain oxidation in the men (p less than 0.001). There was also a 52% higher clearance through glucuronidation in the men (p less than 0.02). In contrast, the clearance through the P-450-mediated ring oxidation was not different between men and women. After administration of simultaneous intravenous doses of hexadeuterium-labeled drug (0.1 mg/kg) to 11 of the subjects, there were no differences between men and women in volume of distribution or half-life. Moreover, there were no sex differences in plasma and blood binding of propranolol. This study thus demonstrates that higher plasma levels of propranolol occur in women than in men after oral doses and suggests that some drug metabolizing enzymes, but not others, are regulated by sex hormones in human beings.