Showing papers by "University of Texas Medical Branch published in 1999"

Cell Activation and Apoptosis by Bacterial Lipoproteins Through Toll-like Receptor-2

Abstract: Apoptosis is implicated in the generation and resolution of inflammation in response to bacterial pathogens. All bacterial pathogens produce lipoproteins (BLPs), which trigger the innate immune response. BLPs were found to induce apoptosis in THP-1 monocytic cells through human Toll-like receptor–2 (hTLR2). BLPs also initiated apoptosis in an epithelial cell line transfected with hTLR2. In addition, BLPs stimulated nuclear factor–κB, a transcriptional activator of multiple host defense genes, and activated the respiratory burst through hTLR2. Thus, hTLR2 is a molecular link between microbial products, apoptosis, and host defense mechanisms.

Comparative Effects of Low and High Doses of the Angiotensin-Converting Enzyme Inhibitor, Lisinopril, on Morbidity and Mortality in Chronic Heart Failure

Abstract: Background—Angiotensin-converting enzyme (ACE) inhibitors are generally prescribed by physicians in doses lower than the large doses that have been shown to reduce morbidity and mortality in patients with heart failure. It is unclear, however, if low doses and high doses of ACE inhibitors have similar benefits. Methods and Results—We randomly assigned 3164 patients with New York Heart Association class II to IV heart failure and an ejection fraction #30% to double-blind treatment with either low doses (2.5 to 5.0 mg daily, n51596) or high doses (32.5 to 35 mg daily, n51568) of the ACE inhibitor, lisinopril, for 39 to 58 months, while background therapy for heart failure was continued. When compared with the low-dose group, patients in the high-dose group had a nonsignificant 8% lower risk of death (P50.128) but a significant 12% lower risk of death or hospitalization for any reason (P50.002) and 24% fewer hospitalizations for heart failure (P50.002). Dizziness and renal insufficiency was observed more frequently in the high-dose group, but the 2 groups were similar in the number of patients requiring discontinuation of the study medication. Conclusions—These findings indicate that patients with heart failure should not generally be maintained on very low doses of an ACE inhibitor (unless these are the only doses that can be tolerated) and suggest that the difference in efficacy between intermediate and high doses of an ACE inhibitor (if any) is likely to be very small. (Circulation. 1999;100:2312-2318.)

Myofibroblasts. I. Paracrine cells important in health and disease.

Abstract: Myofibroblasts are a unique group of smooth-muscle-like fibroblasts that have a similar appearance and function regardless of their tissue of residence. Through the secretion of inflammatory and an...

Identification of CHIP, a Novel Tetratricopeptide Repeat-Containing Protein That Interacts with Heat Shock Proteins and Negatively Regulates Chaperone Functions

Abstract: The chaperone function of the mammalian 70-kDa heat shock proteins Hsc70 and Hsp70 is modulated by physical interactions with four previously identified chaperone cofactors: Hsp40, BAG-1, the Hsc70-interacting protein Hip, and the Hsc70-Hsp90-organizing protein Hop. Hip and Hop interact with Hsc70 via a tetratricopeptide repeat domain. In a search for additional tetratricopeptide repeat-containing proteins, we have identified a novel 35-kDa cytoplasmic protein, carboxyl terminus of Hsc70-interacting protein (CHIP). CHIP is highly expressed in adult striated muscle in vivo and is expressed broadly in vitro in tissue culture. Hsc70 and Hsp70 were identified as potential interaction partners for this protein in a yeast two-hybrid screen. In vitro binding assays demonstrated direct interactions between CHIP and both Hsc70 and Hsp70, and complexes containing CHIP and Hsc70 were identified in immunoprecipitates of human skeletal muscle cells in vivo. Using glutathione S-transferase fusions, we found that CHIP interacted with the carboxy-terminal residues 540 to 650 of Hsc70, whereas Hsc70 interacted with the amino-terminal residues 1 to 197 (containing the tetratricopeptide domain and an adjacent charged domain) of CHIP. Recombinant CHIP inhibited Hsp40-stimulated ATPase activity of Hsc70 and Hsp70, suggesting that CHIP blocks the forward reaction of the Hsc70-Hsp70 substrate-binding cycle. Consistent with this observation, both luciferase refolding and substrate binding in the presence of Hsp40 and Hsp70 were inhibited by CHIP. Taken together, these results indicate that CHIP decreases net ATPase activity and reduces chaperone efficiency, and they implicate CHIP in the negative regulation of the forward reaction of the Hsc70-Hsp70 substrate-binding cycle.

Efficient Bypass of a Thymine-Thymine Dimer by Yeast DNA Polymerase, Polη

Abstract: The RAD30 gene of the yeast Saccharomyces cerevisiae is required for the error-free postreplicational repair of DNA that has been damaged by ultraviolet irradiation. Here, RAD30 is shown to encode a DNA polymerase that can replicate efficiently past a thymine-thymine cis-syn cyclobutane dimer, a lesion that normally blocks DNA polymerases. When incubated in vitro with all four nucleotides, Rad30 incorporates two adenines opposite the thymine-thymine dimer. Rad30 is the seventh eukaryotic DNA polymerase to be described and hence is named DNA polymerase eta.

hRAD30 mutations in the variant form of xeroderma pigmentosum.

Abstract: Xeroderma pigmentosum (XP) is an autosomal recessive disease characterized by a high incidence of skin cancers. YeastRAD30encodes a DNA polymerase involved in the error-free bypass of ultraviolet (UV) damage. Here it is shown that XP variant (XP-V) cell lines harbor nonsense or frameshift mutations in hRAD30, the human counterpart of yeastRAD30. Of the eight mutations identified, seven would result in a severely truncated hRad30 protein. These results indicate that defects in hRAD30 cause XP-V, and they suggest that error-free replication of UV lesions by hRad30 plays an important role in minimizing the incidence of sunlight-induced skin cancers.

Defining Lives: Occupation as Identity: An Essay on Competence, Coherence, and the Creation of Meaning

Abstract: This article presents a view of occupation as the principal means through which people develop and express their personal identities. Based on a review of theory and research, it proposes that identity is instrumental to social life because it provides a context for deriving meaning from daily experiences and interpreting lives over time. The article proposes that identity also provides a framework for goal-setting and motivation. It is asserted that competence in the performance of tasks and occupations contributes to identity-shaping and that the realization of an acceptable identity contributes to coherence and well-being. Within this framework, it is postulated that performance limitations and disfigurement that sometimes result from illness or injury have identity implications that should be recognized by occupational therapy practitioners. By virtue of their expertise in daily living skills, occupational therapy practitioners are well positioned to help address the identity challenges of those whom they serve. In so doing, they make an important contribution to meaning and well-being.

Heritability of nociception I: responses of 11 inbred mouse strains on 12 measures of nociception.

Abstract: It is generally acknowledged that humans display highly variable sensitivity to pain, including variable responses to identical injuries or pathologies. The possible contribution of genetic factors has, however, been largely overlooked. An emerging rodent literature documents the importance of genotype in mediating basal nociceptive sensitivity, in establishing a predisposition to neuropathic pain following neural injury, and in determining sensitivity to pharmacological agents and endogenous antinociception. One clear finding from these studies is that the effect of genotype is at least partially specific to the nociceptive assay being considered. In this report we begin to systematically describe and characterize genetic variability of nociception in a mammalian species, Mus musculus. We tested 11 readily-available inbred mouse strains (129/J, A/J, AKR/J, BALB/cJ, C3H/HeJ, C57BL/6J, C58/J, CBA/J, DBA/2J, RIIIS/J and SM/J) using 12 common measures of nociception. These included assays for thermal nociception (hot plate, Hargreaves' test, tail withdrawal), mechanical nociception (von Frey filaments), chemical nociception (abdominal constriction, carrageenan, formalin), and neuropathic pain (autotomy, Chung model peripheral nerve injury). We demonstrate the existence of clear strain differences in each assay, with 1.2 to 54-fold ranges of sensitivity. All nociceptive assays display moderate-to-high heritability (h2 = 0.30-0.76) and mediation by a limited number of apparent genetic loci. Data comparing inbred strains have considerable utility as a tool for understanding the genetics of nociception, and a particular relevance to transgenic studies.

Postexercise net protein synthesis in human muscle from orally administered amino acids.

Abstract: We examined the response of net muscle protein synthesis to ingestion of amino acids after a bout of resistance exercise. A primed, constant infusion of L-[ring-2H5]phenylalanine was used to measure net muscle protein balance in three male and three female volunteers on three occasions. Subjects consumed in random order 1 liter of 1) a mixed amino acid (40 g) solution (MAA), 2) an essential amino acid (40 g) solution (EAA), and 3) a placebo solution (PLA). Arterial amino acid concentrations increased approximately 150-640% above baseline during ingestion of MAA and EAA. Net muscle protein balance was significantly increased from negative during PLA ingestion (-50 +/- 23 nmol. min-1. 100 ml leg volume-1) to positive during MAA ingestion (17 +/- 13 nmol. min-1. 100 ml leg volume-1) and EAA (29 +/- 14 nmol. min-1. 100 ml leg volume-1; P < 0.05). Because net balance was similar for MAA and EAA, it does not appear necessary to include nonessential amino acids in a formulation designed to elicit an anabolic response from muscle after exercise. We concluded that ingestion of oral essential amino acids results in a change from net muscle protein degradation to net muscle protein synthesis after heavy resistance exercise in humans similar to that seen when the amino acids were infused.

Myofibroblasts. II. Intestinal subepithelial myofibroblasts

Abstract: Intestinal subepithelial myofibroblasts (ISEMF) and the interstitial cells of Cajal are the two types of myofibroblasts identified in the intestine. Intestinal myofibroblasts are activated and prol...

Prevalence of various respiratory viruses in the middle ear during acute otitis media

Abstract: Background Vaccines against respiratory viruses may be able to reduce the frequency of acute otitis media. Although the role of respiratory viruses in the pathogenesis of acute otitis media is well established, the relative importance of various viruses is unknown. Methods We determined the prevalence of various respiratory viruses in the middle-ear fluid in 456 children (age, two months to seven years) with acute otitis media. At enrollment and after two to five days of antibiotic therapy, specimens of middle-ear fluid and nasal-wash specimens were obtained for viral and bacterial cultures and the detection of viral antigens. The viral cause of the infections was also assessed by serologic studies of serum samples obtained during the acute illness and convalescence. Results A specific viral cause of the respiratory tract infections was identified in 186 of the 456 children (41 percent). Respiratory syncytial virus was the most common virus identified in middle-ear fluid: it was detected in the middle-ear...

The effectiveness of condoms in reducing heterosexual transmission of HIV.

Abstract: This cross-sectional and longitudinal study examines the overall effectiveness of condoms in reducing heterosexual transmission of HIV. Data on condom usage and HIV serology was obtained from 25 published studies of serodiscordant heterosexual couples. Condom usage was rated as always (in 100% of acts of intercourse) sometimes (1-99% 0-99% or 1-100%) or never (0%). Studies were stratified by design direction of transmission and condom usage group. Condom efficacy was calculated from the HIV transmission rates for always-users and never-users. Results showed that 12 cohort samples gave a consistent HIV incidence of 0.9 per 100 person-years. For 11 cohort samples of never-users incidence was estimated at 6.8 per 100 person-years for male-to-female transmission and 5.9 per 100 for female-to-male transmission. Overall the condoms effectiveness at preventing HIV transmission is estimated to be 87% but it may vary between 60% and 96%.

Water transport revisited

Abstract: Nearly forty years ago Curran & MacIntosh (1962) presented experimental evidence for a model of water transport that would satisfy a question posed by such famous physiologists as Heidenhain and Reed before the turn of the century: how can the intestine accomplish transport of water from one isotonic compartment (the bowel lumen) to another (the blood)? Curran, who was a superb experimentalist as well as a theoretician, had previously shown that water transport bore a linear relationship to solute (Na+) transport. He and MacIntosh then demonstrated that a three-compartment model (see Fig. 1) would allow movement of fluid from compartment I to III as long as compartment II contained a solution hypertonic to I and III, and as long as the permeabilities (reflection coefficients) of the membranes A and B, which separated the compartments, were finite with B greater than A. They used cellophane for membrane A and sintered glass for membrane B in their model. The biological counterparts to these membranes were thought to be the tight junctions (TJ) of the epithelial cells for membrane A, the basement membrane (BM) for membrane B and the intercellular space (ICS) for compartment II. Active Na+ transport along the basolateral membrane of the epithelial cell into the ICS was proposed as the active solute's transport step driving the passive flow of water from I to III. Diamond's ‘standing gradient’ hypothesis of water movement was a later variation of this model (Diamond, 1978). Thus, the mystery of the special driving force, or ‘treibkraft’ moving water across the intestinal wall was solved: it was ‘compartmentalized’ osmotic pressure. Figure 1 Curran and MacIntosh's model system for water transport (right) is shown with proposed biological counterparts in the colonic mucosa (left). SMS, subepithelial myofibroblastic syncytium with reticular fibrils. These models of water transport were adequate to explain isotonic transport, i.e. an absorbant osmolality that was essentially isotonic with the luminal fluid and with the plasma. It was subsequently shown that the distal colon could transport fluid hypertonically, i.e. an absorbate with osmolalities of 500–1000 mosmol (kg H2O)−1. Furthermore, such hypertonic transport was necessary to dehydrate the faecal mass in the distal colon. Naftalin and colleagues have proposed that the development of hypertonic water transport allows the distal colonic crypts to act as suction devices capable of dehydrating faeces (Naftalin et al. 1999). Given known hydraulic permeabilities of the epithelial cell membranes and rates of Na+ transport, it has been difficult to imagine how the distal colon could create an osmotic gradient in the ICS sufficient to accomplish the formation of hard faeces. The two papers by Naftalin and colleagues (Naftalin et al. 1999; Naftalin & Pedley, 1999) in this issue of The Journal of Physiology shed light on this question by proposing a role for the myofibroblast-reticular sheath (which they call the fibronexus). This ‘sheath’ forms a second fenestrated ‘membrane’ just under the fenestrated BM in the intestine and probably most epithelial tissues (Toyoda et al. 1997). Heretofore, this myofibroblastic syncytium had been thought only to influence intestinal secretion through prostaglandin (cyclic AMP)-mediated sensitization of intestinal epithelial cells to Ca2+-mediated secretogogues (Berschneider & Powell, 1992). Using confocal microscopy to identify this ‘sheath’ and a fluorescent probe for Na+, these investigators show that it presents a diffusion barrier to Na+ that correlates well with the gut segments that are able to transport hypertonically. These experiments suggest that the reflection coefficient of the BM is such that this barrier is adequate for isotonic transport, but that the myofibroblast-reticular sheath serves as an additional diffusion barrier in series with the BM in order to accomplish hypertonic transport. Alternatively, it may be that it is the myofibroblast-reticular sheath, and not the BM, which represents the basolateral diffusion barrier for either isotonic or hypertonic transport. The investigators have also shown a correlation between the barrier function of this sheath and a high renin-angiotensin II-aldosterone state brought about by dietary Na+ depletion. It has been previously known that such a state greatly increases distal colonic Na+ transport by increasing the resistance of the tight junctions and by increasing expression of amiloride-sensitive Na+ channels and Na+,K+-ATPase on the apical and basolateral membranes of the distal colonocyte. Naftalin and colleagues propose that this sodium depletion state also leads to greater osmotic transport, through angiotensin II- or aldosterone-induced activation of the myofibroblasts with increased synthesis and secretion of reticulin fibrils, resulting in changes in the reflection coefficient of this myofibroblast-reticular membrane. These investigators give increased verification and clearer biological counterparts to a model of transport proposed nearly half a century ago. It remains to be determined if this myofibroblast-reticular sheath has such a transport function in all electrolyte and water transporting epithelia. It appears that the syncytium of myofibroblasts exists under the epithelial BM in all transporting epithelia where it has contractile functions and growth, differentiation and wound repair functions. This syncytium will be the subject of considerable investigation over the next few years.

Oral amino acids stimulate muscle protein anabolism in the elderly despite higher first-pass splanchnic extraction

Abstract: Muscle protein synthesis and breakdown and amino acid transport were measured in 7 healthy young (30 ± 2 yr) and 8 healthy elderly (71 ± 2 yr) volunteers in the postabsorptive state and during the ...

Dorsal root potentials and dorsal root reflexes: a double-edged sword.

Abstract: The nature of dorsal root reflexes (DRRs) and their possible role in peripheral inflammation and the consequent hyperalgesia are reviewed. The history of DRRs and the relationship of DRRs to primary afferent depolarization and presynaptic inhibition in pathways formed by both large and fine afferents are discussed. Emphasis is placed on the mechanisms underlying primary afferent depolarization, including the anatomical arrangement of the synapses involved, how depolarization can result in inhibition by decreasing transmitter release, the role of excitatory amino acids and GABA, the manner in which the equilibrium potential for chloride ions is determined in primary afferent fibers, and forms of presynaptic inhibition that do not utilize GABA(A) receptors. There is then a discussion of neurogenic inflammation, including the role of the release of neuropeptides such as substance P and calcitonin gene-related peptide from sensory nerve endings. Evidence is reviewed that links DRRs to a substantial part of the swelling of the knee joint in acute experimental arthritis and to the flare reaction in the skin following intradermal injection of capsaicin. Possible mechanisms by which the level of DRR activity might be enhanced following inflammation are suggested. The consequences of this increase in DRRs may include exacerbation of hyperalgesia as well as of peripheral inflammation. The conversion of an inhibitory process, presynaptic inhibition, to an excitatory one by DRRs can thus lead to pathological consequences.

Long term prevention of allergic lung inflammation in a mouse model of asthma by CpG oligodeoxynucleotides.

Abstract: Asthma is an inflammatory disease of the airways that is induced by Th2 cytokines and inhibited by Th1 cytokines. Despite a steady increase in the incidence, morbidity, and mortality from asthma, no current treatment can reduce or prevent asthma for a prolonged period. We examined the ability of unmethylated CpG oligodeoxynucleotides (ODN), which are potent inducers of Th1 cytokines, to prevent the inflammatory and physiological manifestations of asthma in mice sensitized to ragweed allergen. Administration of CpG ODN 48 h before allergen challenge increased the ratio of IFN-gamma to IL-4 secreting cells, diminished allergen-induced eosinophil recruitment, and decreased the number of ragweed allergen-specific IgE-producing cells. These effects of CpG ODN were sustained for at least 6 wk after its administration. Furthermore, there was a vigorous Th1 memory response to the recall Ag, inhibition of peribronchial and perivascular lung inflammation, and inhibition of bronchial hyperresponsiveness 6 wk after administration of CpG ODN. Administration of CpG ODN in IFN-gamma -/- mice failed to inhibit eosinophil recruitment, indicating a critical role of IFN-gamma in mediating these effects. This is the first report of a treatment that inhibits allergic lung inflammation in presensitized animals for a prolonged period and thus has relevance to the development of an effective long term treatment for asthma.

Initiation of base excision repair: glycosylase mechanisms and structures.

Abstract: The base excision repair pathway is an organism's primary defense against mutations induced by oxidative, alkylating, and other DNA-damaging agents. This pathway is initiated by DNA glycosylases that excise the damaged base by cleavage of the glycosidic bond between the base and the DNA sugar-phosphate backbone. A subset of glycosylases has an associated apurinic/apyrimidinic (AP) lyase activity that further processes the AP site to generate cleavage of the DNA phosphate backbone. Chemical mechanisms that are supported by biochemical and structural data have been proposed for several glycosylases and glycosylase/AP lyases. This review focuses on the chemical mechanisms of catalysis in the context of recent structural information, with emphasis on the catalytic residues and the active site conformations of several cocrystal structures of glycosylases with their substrate DNAs. Common structural motifs for DNA binding and damage specificity as well as conservation of acidic residues and amino groups for catalysis are discussed.

Angiotensin II induces interleukin-6 transcription in vascular smooth muscle cells through pleiotropic activation of nuclear factor-κB transcription factors

Abstract: Interleukin-6 (IL-6) is a multifunctional cytokine expressed by angiotensin II (Ang II)-stimulated vascular smooth muscle cells (VSMCs) that functions as an autocrine growth factor. In this study, we analyze the mechanism for Ang II-inducible IL-6 expression in quiescent rat VSMCs. Stimulation with the Ang II agonist Sar1 Ang II (100 nmol/L) induced transcriptional expression of IL-6 mRNA transcripts of 1.8 and 2.4 kb. In transient transfection assays of IL-6 promoter/luciferase reporter plasmids, Sar1 Ang II treatment induced IL-6 transcription in a manner completely dependent on the nuclear factor-kappaB (NF-kappaB) motif. Sar1 Ang II induced cytoplasmic-to-nuclear translocation of the NF-kappaB subunits Rel A and NF-kappaB1 with parallel changes in DNA-binding activity in a biphasic manner, which produced an early peak at 15 minutes followed by a nadir 1 to 6 hours later and a later peak at 24 hours. The early phase of NF-kappaB translocation was dependent on weak simultaneous proteolysis of the IkappaBalpha and beta inhibitors, whereas later translocation was associated with enhanced processing of the p105 precursor into the mature 50-kDa NF-kappaB1 form. Pretreatment with a potent inhibitor of IkappaBalpha proteolysis, TPCK, completely blocked Sar1 Ang IIAng II-induced NF-kappaB activation and induction of endogenous IL-6 gene expression, which indicated the essential role of NF-kappaB in mediating IL-6 expression. We conclude that Ang II is a pleiotropic regulator of the NF-kappaB transcription factor family and may be responsible for activating the expression of cytokine gene networks in VSMCs.

Gender Differences in the Epidemiology and Treatment of Anxiety Disorders

Abstract: Women are more likely than men to develop anxiety disorders. Yet, relatively few studies have investigated whether women with anxiety disorders have characteristics that are distinct from those of men with the same disorders. The cause of the enhanced vulnerability to anxiety for women remains largely undetermined. Recent data suggest that female reproductive hormones and related cycles may play an important role. In addition to etiologic functions, reproductive hormones may substantially influence the clinical course of preexisting anxiety conditions in women. Psychotropic medications are more likely to be prescribed to women, and gender differences have been identified in the pharmacokinetics of psychotropic medication. Yet, relatively few systematic data are available concerning the potential clinical relevance or possible treatment implications of gender differences in the treatment of women with anxiety disorders. This article reviews the unique characteristics of primary anxiety disorders in women, summarizes the neurobiological effects associated with estrogen and progesterone, discusses gender differences in medication metabolism and the potential relevance of these differences in the pharmacologic management of women with anxiety disorders, and reviews issues specific to women (e.g., hormone therapy, oral contraceptives, menstrual cycle, pregnancy, lactation) that may impact treatment with psychotropic medication.

Functional vision and corneal changes after laser in situ keratomileusis determined by contrast sensitivity, glare testing, and corneal topography.

Abstract: Purpose To demonstrate the functional vision and corneal changes following laser in situ keratomileusis (LASIK) determined by contrast sensitivity, glare testing, and corneal topography. Setting University of Texas Medical School, Houston, Texas, USA. Methods Seven patients ranging in age from 20 to 61 years who had bilateral LASIK were evaluated preoperatively and 1 day, 1 week, and 1 and 6 months postoperatively. Visual acuity, using letters on the Baylor Visual Acuity Testor (BVAT) at 98% (standard acuity) and 13% contrast, and the contrast threshold were determined at 3 light levels (darkness, medium brightness acuity testor [BAT], high BAT). Pupil sizes were measured at each level, and corneal topography was performed at each visit. Results The greatest changes were found 1 day postoperatively: The contrast threshold worsened by a mean of 0.6 lines ± 1.0 (SD) (P = .05) in darkness, 0.4 ± 0.7 lines (P = .05) at medium BAT, and 0.8 ± 0.7 lines (P = .002) at high BAT. The 98% contrast acuity decreased a mean of 1.4 ± 1.6 lines (P = .01) in darkness, 1.0 ± 2.0 lines (P = .09) at medium BAT, and 0.8 ± 2.3 lines (P = .22) at high BAT. The 13% contrast acuity decreased a mean of 2.2 ± 2.6 lines (P = .01) in darkness, 1.3 ± 1.9 lines (P = .02) at medium BAT, and 1.4 ± 2.5 lines (P = .07) at high BAT. The predicted corneal acuity (PCA) obtained from corneal topography decreased by a mean of 3.3 ± 3.1 lines (P = .002), and the asphericity (Q-value) increased by an average of +0.35 ± 0.67 (P = .07). All values returned to the preoperative levels by 1 week except PCA, asphericity, visual acuity at 13%, and contrast threshold in darkness, which improved slightly but had not returned to baseline by 6 months. The 98% contrast acuity at medium BAT improved by 0.2 ± 1.0 lines (P = .34) and 0.3 ± 0.8 lines (P = .16) at high BAT at 1 month. The 98% contrast acuity values remained 0.3 lines over baseline through 6 months. Corneal topography showed that all corneas became oblate after LASIK to a mean Q-value of +0.47 ± 0.40 (P Conclusions Functional vision changes do occur after LASIK. The optical quality of the cornea is reduced and the asphericity becomes oblate. Changes in functional vision worsen as the target contrast diminishes and the pupil size increases. These findings indicate that the oblate shape of the cornea following LASIK is the predominant factor in the functional vision decrease.

Resistance training reduces the acute exercise-induced increase in muscle protein turnover.

Abstract: We examined the effect of resistance training on the response of mixed muscle protein fractional synthesis (FSR) and breakdown rates (FBR) by use of primed constant infusions of [2H5]phenylalanine and [15N]phenylalanine, respectively, to an isolated bout of pleiometric resistance exercise. Trained subjects, who were performing regular resistance exercise (trained, T; n = 6), were compared with sedentary, untrained controls (untrained, UT; n = 6). The exercise test consisted of 10 sets (8 repetitions per set) of single-leg knee flexion (i.e., pleiometric muscle contraction during lowering) at 120% of the subjects' predetermined single-leg 1 repetition maximum. Subjects exercised one leg while their contralateral leg acted as a nonexercised (resting) control. Exercise resulted in an increase, above resting, in mixed muscle FSR in both groups (UT: rest, 0.036 +/- 0.002; exercise, 0.0802 +/- 0.01; T: rest, 0.045 +/- 0.004; exercise, 0.067 +/- 0.01; all values in %/h; P < 0.01). In addition, exercise resulted in an increase in mixed muscle FBR of 37 +/- 5% (rest, 0.076 +/- 0.005; exercise, 0.105 +/- 0.01; all values in %/h; P < 0.01) in the UT group but did not significantly affect FBR in the T group. The resulting muscle net balance (FSR - FBR) was negative throughout the protocol (P < 0.05) but was increased in the exercised leg in both groups (P < 0.05). We conclude that pleiometric muscle contractions induce an increase in mixed muscle protein synthetic rate within 4 h of completion of an exercise bout but that resistance training attenuates this increase. A single bout of pleiometric muscle contractions also increased the FBR of mixed muscle protein in UT but not in T subjects.

Systemic lupus erythematosus in three ethnic groups: III A comparison of characteristics early in the natural history of the LUMINA cohort:

Abstract: Aim: To determine and contrast the socioeconomic-demographic and clinical features of patients with recent onset (5 y) systemic lupus erythematosus (SLE) from three ethnic groups, Hispanic, African-American and Caucasian (H, AA, C).Subjects and methods: SLE cases (American College of Rheumatology criteria) (incident (n ‘ 56), prevalent (n ‘ 173)), were enrolled in a longitudinal study at The University of Alabama at Birmingham, The University of Texas-Houston Health Science Center and The University of Texas Medical Branch at Galveston. Socioeconomic-demographic, clinical, immunological, behavioral and psychological data were obtained using validated instruments and standard laboratory techniques, and compared.Results: 70 H, 88 AA and 71 C SLE patients constitutethis cohort. H and AA patients were younger and of lower socioeconomic-demographic status. They also had evidence of more frequent organ system involvement (renal, cardiovascular), more auto-antibodies, more active disease (after adjusting for dis...

A Phylogenetically Conserved Stem-Loop Structure at the 5′ Border of the Internal Ribosome Entry Site of Hepatitis C Virus Is Required for Cap-Independent Viral Translation

Abstract: Hepatitis C virus (HCV) initiates translation of its polyprotein under the control of an internal ribosome entry site (IRES) that comprises most of the 341-nucleotide (nt) 5′ nontranslated RNA (5′NTR). A comparative analysis of related flaviviral sequences suggested that an RNA segment for which secondary structure was previously ill defined (domain II, nt 44 to 118) forms a conserved stem-loop that is located at the 5′ border of the HCV IRES and thus may function in viral translation. This prediction was tested by a mutational analysis of putative helical structures that examined the impact of both covariant and noncovariant nucleotide substitutions on IRES activity in vivo and in vitro. Results of these experiments provide support for predicted base pair interactions between nt 44 to 52 and 111 to 118 and between nt 65 to 70 and 97 to 102 of the HCV 5′NTR. Substitutions at either nt 45 and 46 or nt 116 and 117 resulted in reciprocal changes in V1 nuclease cleavage patterns within the opposing strand of the putative helix, consistent with the predicted base pair interactions. IRES activity was highly dependent on maintenance of the stem-loop II structure but relatively tolerant of covariant nucleotide substitutions within predicted helical segments. Sequence alignments suggested that the deduced domain II structure is conserved within the IRESs of pestiviruses as well as the novel flavivirus GB virus B. Despite marked differences in primary nucleotide sequence within conserved helical segments, the sequences of the intervening single-stranded loop segments are highly conserved in these different viruses. This suggests that these segments of the viral RNA may interact with elements of the host translational machinery that are broadly conserved among different mammalian species.

Impulsive and premeditated aggression: a factor analysis of self-reported acts.

Abstract: Although aggression research in general has been hampered by a lack of objective measurements of aggressive acts, two types of aggressive acts, impulsive vs. premeditated, have been studied extensively in recent years. These two types of aggression have been primarily measured by structured or semi-structured interviews. The current study was designed to assess the construct validity of these two types of aggression using a self-report questionnaire which included items gleaned from the content of interviews used in past studies. For this study, 216 college students assessed their own aggressive acts rather than answering general questions about aggression. The students were not significantly different from normative sample groups on self-report measures of impulsiveness, aggression, and anger/hostility. A PCA factor analysis with a promax rotation of the items on the self-report questionnaire identified four factors: impulsive aggression; mood on the day the act occurred; premeditated aggression; and agitation. Thus, impulsive and premeditated aggression are independent constructs which exist in varying degrees among these 'normal' persons in a non-clinical sample. Impulsive aggression was characterized in part by feelings of remorse following the acts and by thought confusion. Premeditated aggression was related to social gain and dominance.

High-level variability in the ORF-K1 membrane protein gene at the left end of the Kaposi's sarcoma-associated herpesvirus genome defines four major virus subtypes and multiple variants or clades in different human populations.

Abstract: Infection with Kaposi's sarcoma (KS)-associated herpesvirus (KSHV) or human herpesvirus 8 (HHV8) is common in certain parts of Africa, the Middle East, and the Mediterranean, but is rare elsewhere, except in AIDS patients. Nevertheless, HHV8 DNA is found consistently in nearly all classical, endemic, transplant and AIDS-associated KS lesions as well as in some rare AIDS-associated lymphomas. The concept that HHV8 genomes fall into several distinct subgroups has been confirmed and refined by PCR DNA sequence analysis of the ORF-K1 gene encoding a highly variable glycoprotein related to the immunoglobulin receptor family that maps at the extreme left-hand end of the HHV-8 genome. Among more than 60 different tumor samples from the United States, central Africa, Saudi Arabia, Taiwan, and New Zealand, amino acid substitutions were found at a total of 62% of the 289 amino acid positions. These variations defined four major subtypes and 13 distinct variants or clades similar to those found for the HIV ENV protein. The B and D subtype ORF-K1 proteins differ from the A and C subtypes by 30 and 24%, respectively, whereas A and C differ from each other by 15%. In all cases tested, multiple samples from the same patient were identical. Examples of the B subtype were found almost exclusively in KS patients from Africa or of African heritage, whereas the rare D subtypes were found only in KS patients of Pacific Island heritage. In contrast, C subtypes were found predominantly in classic KS and in iatrogenic and AIDS KS in the Middle East and Asia, whereas U.S. AIDS KS samples were primarily A1, A4, and C3 variants. We conclude that this unusually high diversity, in which 85% of the nucleotide changes lead to amino acid changes, reflects some unknown powerful biological selection process that has been acting preferentially on this early lytic cycle membrane signalling protein. Two distinct levels of ORF-K1 variability are recognizable. Subtype-specific variability indicative of long-term evolutionary divergence is both spread throughout the protein as well as concentrated within two 40-amino-acid extracellular domain variable regions (VR1 and VR2), whereas intratypic variability localizes predominantly within a single 25-amino-acid hypervariable Cys bridge loop and apparently represents much more recent changes that have occurred even within specific clades. In contrast, numerous extracellular domain glycosylation sites and Cys bridge residues as well as the ITAM motif in the cytoplasmic domain are fully conserved. Overall, we suggest that rather than being a newly acquired human pathogen, HHV8 is an ancient human virus that is preferentially transmitted in a familial fashion and is difficult to transmit horizontally in the absence of immunosuppression. The division into the four major HHV8 subgroups is probably the result of isolation and founder effects associated with the history of migration of modern human populations out of Africa over the past 35,000 to 60,000 years.