Assessing genetic-based therapies for AIDS using the simian immunodeficiency virus

Biochemical assays have demonstrated the existence of hormone receptors in lung tissue from patients with pulmonary lymphangiomyomatosis (LAM). This finding is the biologic corollary to the finding that LAM responds to hormonal therapy. We have examined lung tissue from two patients with LAM for estrogen and progesterone receptors by immunohistochemistry and a biochemical assay. Although specimens from both patients were negative for estrogen receptor activity by the biochemical assay, positive stain of estrogen receptors was observed in both patients with immunohistochemistry.     

Chronic phenytoin induced impairment of learning and memory with associated changes in brain acetylcholine esterase activity and monoamine levels

Groups of adult, male, Wistar rats were administered phenytoin (DPH) at 5, 12.5, 25, 50, or 75 mg/kg i.p. for 21 days. The learning and memory of these rats were assessed using the T-maze and passive avoidance tests. The plasma DPH levels, acetylcholine esterase (AChE) activity in different brain regions, and the levels of monoamines in the hippocampus were measured. The results indicate that DPH below the therapeutic plasma level did not significantly impair learning and memory. Correspondingly, no changes were noted in the brain 5-HT or AChE activity. However, DPH, at therapeutic plasma concentrations (i.e., 10.5 micrograms/ml in the dosage range of 50 and 75 mg/kg, respectively), significantly impaired learning and memory in rats. The impaired learning and memory functions were associated with increased 5-HT levels and decreased AChE activity in the hippocampus. With a dose of 75 mg/kg DPH, there was a reduction in the AChE activity in the striatum, in addition to hippocampus. It is conjectured that the neurochemical changes brought about by DPH at therapeutic plasma levels may account for the impairment of learning, memory, and cognitive functions in epilepsy.     

Compliance with primary prevention in private practice: creating a tobacco-free environment

A sample of private orthodontic practices (n = 40) from a controlled trial for clinician-initiated tobacco-use prevention was used to test the effectiveness of preventive medicine representative (PMR) visits in creating and maintaining an anti-tobacco office environment. Clinical staff of 20 offices, randomly assigned to the experimental group, were trained by a PMR on the use of anti-tobacco materials (no-smoking signs, posters, and print materials). Twenty control-group offices did not receive any training or special treatment. Subsequently, experimental-group offices were visited by a PMR once every three months and were telephoned six weeks after each visit over a 12-month period. During visits and phone calls, PMRs prompted offices to order anti-tobacco materials. Visits served to introduce offices to new materials and to encourage their continued use. Data from direct observations and self-report measures showed significant differences between experimental and control offices for display of anti-tobacco materials at 1.5 months and 12 months (P < .001). Results suggest that PMR visits may serve as an effective method of introducing and maintaining preventive medicine procedures in clinical environments.     

Asymmetrical interaction of GroEL and GroES in the ATPase cycle of assisted protein folding

The chaperonins GroEL and GroES of Escherichia coli facilitate protein folding in an adenosine triphosphate (ATP)-dependent reaction cycle. The kinetic parameters for the formation and dissociation of GroEL-GroES complexes were analyzed by surface plasmon resonance. Association of GroES and subsequent ATP hydrolysis in the interacting GroEL toroid resulted in the formation of a stable GroEL:ADP:GroES complex. The complex dissociated as a result of ATP hydrolysis in the opposite GroEL toroid, without formation of a symmetrical GroEL:(GroES)2 intermediate. Dissociation was accelerated by the addition of unfolded polypeptide. Thus, the functional chaperonin unit is an asymmetrical GroEL:GroES complex, and substrate protein plays an active role in modulating the chaperonin reaction cycle.     

LEC18, a dominant Chinese hamster ovary glycosylation mutant synthesizes N-linked carbohydrates with a novel core structure

The dominant Chinese hamster ovary cell glycosylation mutant, LEC18, was selected for resistance to pea lectin (Pisum sativum agglutinin (PSA)). Lectin binding studies show that LEC18 cells express altered cell surface carbohydrates with markedly reduced binding to 125I-PSA and increased binding to 125I-labeled Datura stramonium agglutinin (DSA) compared with parental cells. Desialylated [3H]Glc-labeled LEC18 cellular glycopeptides that did not bind to concanavalin A-Sepharose exhibited an increased proportion of species that were bound to DSA-agarose. Most of these glycopeptides bound to ricin-agarose and were unique to LEC18 cells. This fraction was purified from approximately 10(10) cells and shown by 1H NMR spectroscopy and methylation linkage analysis to contain novel N-linked structures. Digestion of these glycopeptides with mixtures of beta-D-galactosidases and N-acetyl-beta-D-glucosaminidases gave core glycopeptides that, in contrast to cores from parental cells, were mainly not bound to concanavalin A-Sepharose or to PSA-agarose. 1H NMR spectroscopy, matrix-assisted laser desorption ionization/time of flight mass spectrometry, electrospray mass spectrometry, and collision-activated dissociation mass spectrometry showed that the LEC18 core glycopeptides contained a new GlcNAc residue that substitutes the core GlcNAc residues. Methylation linkage analysis of the parent compound provided evidence that the GlcNAc is linked at O-6 to give the following novel, N-linked core structure. [formula: see text]     

Immunoglobulin levels in populations with low hemoglobin levels: study of five tribes of central India

Average hemoglobin levels for 424 individuals belonging to 5 tribes of central India vary between 10.64 g/dl and 11.30 g/dl among males and between 9.62 g/dl and 9.97 g/dl among females. These ranges indicate the poor state of health and nutrition in these tribes. Three immunoglobulin levels (IgG, IgA, and IgM) measured in a subset of the 424 individuals reveal that immunoglobulin and hemoglobin levels are inversely related to some extent. Levels of all three classes of immunoglobulins were found to be significantly correlated. This suggests that humoral immunity is not impaired even under acute nutritional stress.     

A study on 3D Monte Carlo modeling of photon propagation through tissue

Monte Carlo techniques have become popular in modeling of the random events with advantage of powerful computing systems. Especially they have been applied to simulate processes involving random behavior such as diffusion of the Gamma rays through matter and electron concentrations in semiconductors. Recent medical innovations such as Computer Automated Tomography (CAT) and Positron Emission Tomography (PET) are ideal for Monte Carlo modeling techniques. This paper presents derivation and results of the three dimensional Monte Carlo simulation. The results are presented for tissue interactions with photons at wavelength of 207 nm X rays and 630 nm red light. Resulting values of model tissue have been interpolated and mapped into two-dimensional pattern in gray tone. Combination of two-dimensional patterns allow a reconstruction in three dimensions.