Type-specific neutralization of the human immunodeficiency virus with antibodies to env-encoded synthetic peptides.

A synthetic peptide (SP-10-IIIB) with an amino acid sequence [Cys-Thr-Arg-Pro-Asn-Asn-Asn-Thr-Arg-Lys-Ser-Ile-Arg-Ile-Gln-Arg-Gly-Pro -Pro-Gly-(Tyr); amino acids 303-321] from the human immunodeficiency virus (HIV) isolate human T-cell lymphotropic virus type III (HTLV-III) HTLV-IIIB envelope glycoprotein gp120 was coupled to tetanus toxoid and used to raise goat antibodies to HIV gp120. Goat anti-SP-10-IIIB serum bound to the surface of HTLV-IIIB-infected CEM T cells but not to the surface of HTLV-IIIRF-infected or uninfected CEM T cells. Anti-SP-10-IIIB antibodies also selectively bound to gp120 from lysates of HTLV-IIIB cells in immunoblot assays. Twenty-one percent of sera (28 of 175) from patients seropositive for HIV contained antibodies that reacted with SP-10-IIIB in RIA. Human anti-SP-10-IIIB antibodies affinity purified from acquired immunodeficiency syndrome (AIDS) patient serum bound to HTLV-IIIB-infected cells and immunoprecipitated gp120. Goat antibodies to SP-10-IIIB neutralized HTLV-IIIB (80% neutralization titer of 1/600), inhibited HTLV-IIIB-induced syncytium formation, but did not neutralize HIV isolates HTLV-IIIRF or HTLV-IIIMN or inhibit syncytium formation with these isolates. Also, goat antiserum to an homologous synthetic peptide [SP-10-IIIRF(A), (Cys)-Arg-Lys-Ser-Ile-Thr-Lys-Gly-Pro-Gly-Arg-Val-Ile-Tyr] from gp120 of HIV isolate HTLV-IIIRF inhibited syncytium formation by HTLV-IIIRF, but did not inhibit syncytium formation by HTLV-IIIB or by HTLV-IIIMN. Thus, the amino acid sequences of SP-10-IIIB and SP-10-IIIRF(A) define homologous regions of gp120 that are important in type-specific virus neutralization. The identification of these type-specific neutralizing epitopes should facilitate the design of a polyvalent, synthetic vaccine for AIDS.     

Inconsistent treatment estimates from mis‐specified logistic regression analyses of randomized trials

When the difference between treatments in a clinical trial is estimated by a difference in means, then it is well known that randomization ensures unbiassed estimation, even if no account is taken of important baseline covariates. However, when the treatment effect is assessed by other summaries, for example by an odds ratio if the outcome is binary, then bias can arise if some covariates are omitted, regardless of the use of randomization for treatment allocation or the size of the trial. We present accurate closed‐form approximations for this asymptotic bias when important normally distributed covariates are omitted from a logistic regression. We compare this approximation with ones in the literature and derive more convenient forms for some of these existing results. The expressions give insight into the form of the bias, which simulations show is usable for distributions other than the normal. The key result applies even when there are additional binary covariates in the model. Copyright © 2015 John Wiley & Sons, Ltd.     

Determinants of turnover among low wage earners in long term care: the role of manager-employee relationships

The demand for Long-Term Care (LTC) is steadily increasing as Baby Boomers age and enter retirement. High turnover rates among employees in LTC creates challenges for supervisors and administrators, and can negatively impact quality of care. This study examines manager-subordinate relationship quality using Leader-Member Exchange Theory (LMX) as an antecedent to turnover among low-wage earners in the LTC environment. Survey data measuring LMX, job satisfaction, and demographic information was collected at time 1, and turnover data was collected 18 months later at time 2. The results reveal that all four LMX dimensions were rated significantly different among subordinates who left versus those who stayed, however, only the LMX dimension of supervisor loyalty was a significant predictor of turnover among low wage earners. Our study adds a more nuanced view of the reasons low-wage employees turnover, and presents implications for clinical managers and LTC organizations more broadly.     

Lower Monoamine Oxidase-A Total Distribution Volume in Impulsive and Violent Male Offenders with Antisocial Personality Disorder and High Psychopathic Traits: An [11C] Harmine Positron Emission Tomography Study

Antisocial personality disorder (ASPD) often presents with highly impulsive, violent behavior, and pathological changes in the orbitofrontal cortex (OFC) and ventral striatum (VS) are implicated. Several compelling reasons support a relationship between low monoamine oxidase-A (MAO-A), an enzyme that regulates neurotransmitters, and ASPD. These include MAO-A knockout models in rodents evidencing impulsive aggression and positron emission tomography (PET) studies of healthy subjects reporting associations between low brain MAO-A levels and greater impulsivity or aggression. However, a fundamental gap in the literature is that it is unknown whether brain MAO-A levels are low in more severe, clinical disorders of impulsivity, such as ASPD. To address this issue, we applied [¹¹C] harmine PET to measure MAO-A total distribution volume (MAO-A V_T), an index of MAO-A density, in 18 male ASPD participants and 18 age- and sex-matched controls. OFC and VS MAO-A V_T were lower in ASPD compared with controls (multivariate analysis of variance (MANOVA): F_2,33=6.8, P=0.003; OFC and VS MAO-A V_T each lower by 19%). Similar effects were observed in other brain regions: prefrontal cortex, anterior cingulate cortex, dorsal putamen, thalamus, hippocampus, and midbrain (MANOVA: F_7,28=2.7, P=0.029). In ASPD, VS MAO-A V_T was consistently negatively correlated with self-report and behavioral measures of impulsivity (r=−0.50 to −0.52, all P-values<0.05). This study is the first to demonstrate lower brain MAO-A levels in ASPD. Our results support an important extension of preclinical models of impulsive aggression into a human disorder marked by pathological aggression and impulsivity.     

Sexual and Relationship Benefits of a Safer Conception Intervention Among Men with HIV Who Seek to Have Children with Serodifferent Partners in Uganda

AIDS and Behavior - Many men with HIV (MWH) in Uganda desire children, yet seldom receive reproductive counseling related to HIV care. Because men are under engaged in safer conception programming,...     

A comparison between a conventional and a fiberoptic flow-directed thermal dilution pulmonary artery catheter in critically ill patients

Invasive hemodynamic monitoring is frequently required in the management of patients in intensive care units. A fiberoptic flow-directed thermal dilution pulmonary artery catheter capable of continuously monitoring the mixed venous saturation, while more expensive than a conventional pulmonary artery catheter, theoretically could result in better patient care, and might be cost-effective if it resulted either in fewer blood tests being ordered or in less time in the intensive care unit. To test this hypothesis, we designed a randomized trial in our Medical Intensive Care Unit to compare a standard pulmonary artery catheter with a fiberoptic catheter. Twenty-six patients received a standard catheter and 25 patients received the fiberoptic catheter. There were no statistical differences between the groups in age, time in the intensive care unit, number of tests ordered, hours of mechanical ventilator therapy, hours of vasoactive drug therapy, or mortality rate. The only statistically significant differences between the groups were that (1) the fiberoptic catheter required a longer insertion time and (2) there were more technical problems in consistently obtaining the wedge pressure in the patients with the fiberoptic catheters. We conclude that routine substitution of a fiberoptic catheter for the standard pulmonary artery catheter is not indicated.     

The beta cell glucose stimulus-response curve in normal humans assessed by insulin and C-peptide secretion rates

Insulin and C-peptide secretion rates have been measured and compared in 12 nondiabetic subjects to characterize the glucose stimulus-response of B cell secretion in man. On three different days, glucose concentrations were clamped for 150 minutes at 7.5, 10, and 15 mmol/L, respectively. Plasma samples taken during the clamps were assayed for C-peptide and insulin. C-peptide secretion rates were estimated by the technique of deconvolution. Model-based estimation of insulin secretion rates from insulin concentrations yielded concordant results. In response to glucose, C-peptide concentrations rose less quickly than did insulin concentrations, but the estimated first- and second-phase secretion rates were similar when assessed from either the C-peptide or insulin concentrations. First-phase secretion peaks were larger than inspection of the plasma concentration data might suggest, with median values of 1.3, 2.0, and 2.9 nmol/min for C-peptide in response to 7.5, 10, and 15 mmol/L glucose clamp levels, respectively. The second-phase reached steady state by 90 to 120 minutes, with median C-peptide secretion rates of 0.31, 0.56, and 0.85 nmol/min after 120 minutes at 7.5, 10, and 15 mmol/L, respectively. The slopes of the curves of steady-state insulin and C-peptide secretion rates v the four glucose levels (basal plus the three clamp levels) were maximally steep between 7.5 and 10 mmol/L in the majority of subjects, consistent with in vitro sigmoidal responses. A characterization of the secretory response of the B cell of normal humans at different glucose concentrations has been obtained. With appropriate models, insulin secretion rates may be estimated from either plasma insulin or C-peptide concentration data.     

Vasoactive Peptides and Hypertension: Role of Angiotensin Converting Enzyme

Abstract: Angiotensin converting enzyme plays a key role in the hormonal regulation of blood pressure. It is responsible for the production of the vasconstrictor hormonal peptide angiotensin II as well as the destruction of the vasodilator peptide bradykinin. Recently, orally active specific inhibitors of angiotensin converting enzyme have become available. Captopril (SQ14225) blocks angiotensin I and potentiates bradykinin effects in vitro and in vivo. In man it leads to a fall in endogenous plasma angiotensin II , a rise in blood angiotensin I and renin, but no change in blood bradykinin can be detected .
In sodium deplete normal subjects it lowers the blood pressure, but in sodium replete subjects it is without effect. Similarly, it will acutely lower blood pressure in renovascular and accelerated hypertension but not in essential hypertension. The acute hypotensive effect of captopril may therefore be due to inhibition of the renin-angiotensin system .
However, in the long term, it is effective in lowering the blood pressure in patients with essential hypertension, especially when combined with a diuretic. This suggests that the long-term hypotensive effect differs from the short term effect, and involves mechanisms other than inhibition of the renin-angiotensin     

Effects of intravenous glucose on whole body leucine dynamics, studied with 1-13C-leucine, in healthy young and elderly adults

We examined whole body leucine metabolism in healthy young and elderly adults while in the postabsorptive state and during an intravenous glucose administration at two rates. Leucine flux, incorporation into whole body protein, and oxidation were estimated from a continuous intravenous infusion of L-[1-13C]leucine and determination of 13C enrichment in plasma leucine and expired air. Per unit of body weight, leucine flux and rates of incorporation into protein were similar in young and old men. Old women showed lower rates compared with young women. Rates were similar for both age groups when expressed per unit of total body water and/or of muscle protein mass. Intravenous glucose infusion (4 mg . kg-1 . min-1) reduced plasma leucine levels and flux similarly in both age groups. Thus, age-related differences in muscle mass and sensitivity of peripheral tissues to insulin-mediated glucose uptake and metabolism are not paralleled by alterations in whole body leucine kinetics in the postabsorptive state.