Disulfide bond assignment in human interleukin-7 by matrix-assisted laser desorption/ionization mass spectroscopy and site-directed cysteine to serine mutational analysis

Interleukin-7 (IL-7) is a proteinaceous biological response modifier that has a bioactive tertiary structure dependent on disulfide bond formation. Disulfide bond assignments in human (h)IL-7 are based upon the results of matrix-assisted laser desorption/ionization (MALDI) mass spectroscopy and Cys to Ser mutational analyses. A gene encoding the hIL-7 was synthesized incorporating Escherichia coli codon usage bias and was used to express biologically active protein as determined by stimulation of precursor B-cell proliferation. MALDI mass spectroscopic analysis of trypsin-digested hIL-7 was performed and compared with the anticipated results of a simulated tryptic digestion. Many of the anticipated hIL-7 tryptic fragments were detected including one with a molecular mass equivalent to the sum of two polypeptides linked through a disulfide bond formed from Cys residues (Cys3 and Cys142). Subsequently, Cys to Ser substitution mutational analyses were performed. A hIL-7 variant with all six Cys substituted with Ser was found to be biologically inactive (EC50 > 1 x 10(-7) M). In contrast, a family of single disulfide bond-forming variants of hIL-7 were constructed by reintroducing Cys pairs (Cys3-Cys142, Cys35-Cys130, and Cys48-Cys93), and each could stimulate cell proliferation with an EC50 of 4 x 10(-9), 2 x 10(-8), and 2 x 10(-9) M, respectively. In single disulfide bond-forming mutants of hIL-7, the ability to stimulate cell proliferation was abolished in the presence of 2 mM dithiothreitol. The results presented strongly suggest that only a single disulfide bond is required for hIL-7 to form a tertiary structure capable of stimulating precursor B-cell proliferation.     

Psychological interventions to prevent HIV infection are urgently needed: New priorities for behavioral research in the second decade of AIDS.

Behavior change remains the only means for primary prevention of HIV disease. Psychology should take a leading role in efforts to curtail the epidemic, but has not contributed to HIV prevention at a level proportionate to the urgency of the crisis. The authors propose an updated agenda for behavioral research on AIDS-HIV prevention implementing accelerated community trials of promising behavior change models, conducting trials of community-level interventions on a large scale and focused on populations most vulnerable to HIV infections, establishing partnerships between HIV research and community service organizations, integrating efforts from across psychology disciplines to advance and refine HIV prevention interventions, and mobilizing interdisciplinary HIV prevention resources and communication mechanisms to rapidly translate research findings to community and public policy arenas. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Judgment: The Foundation of Professional Success.

Lists of core competencies or critical capabilities are popular and plentiful. This article makes the case that a single core competency or critical capability accounts for professional success: the exercise of judgment. Judgment is the critical determinant of the quality of professional decisions, actions, and evaluations. Practical models of judgment are presented. The elements and dynamics of judgment are detailed. Individual, group, and organization implications are explored. Coaching and consulting interventions are explained. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Reaction of zirconium fluoride glass with water: kinetics of dissolution

When liquid water contacts a zirconium-barium-lanthanum fluoride glass, at least three different processes occur. Barium and zirconium fluoride dissolve into the water, water penetrates into the glass, and zirconium fluoride crystals grow on the glass surface, in static solution. The rate of dissolution, as measured by solution analysis, is possibly controlled by diffusion in the solid surface; surface blockage and surface reactions are other possible kinetic steps involved. Diffusion in solution is not the controlling mechanism. Hydrogen profiles in the glass surface suggest that the penetration rate of water into the glass is controlled by diffusion and a surface reaction.     

Partner violence before and after individually based alcoholism treatment for male alcoholic patients.

This study examined partner violence in the year before and the year after individually based, outpatient alcoholism treatment for 301 married or cohabiting male alcoholic patients and used a demographically matched nonalcoholic comparison sample. In the year before treatment, 56% of the alcoholic patients had been violent toward their female partner, 4 times the rate of 14% in the comparison sample. In the year after treatment, violence decreased significantly to 25% of the alcoholic sample but remained higher than in the comparison group. Among remitted alcoholics after treatment, violence prevalence of 15% was nearly identical to the comparison sample and half the rate among relapsed patients (32%). Thus, partner violence decreased after alcoholism treatment, and clinically significant violence reductions occurred for patients whose alcoholism was remitted after treatment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Human papillomavirus-specific serologic response in vulvar neoplasia

We describe a case of positional dyspnea due to compression of the tracheobronchial tree by an extensive thoracic aneurysm. In a 77-year-old woman with long-standing systemic hypertension, intermittent anterior chest pain gradually developed over several years. She had no history of asthma or thoracic trauma. She was admitted to our hospital because of sudden, severe shortness of breath. The breathlessness was markedly worse when she lay on her back or on her right side. On physical examination, she was in acute respiratory distress with cyanosis, severe hypertension (180/110 mmHg), tachycardia, and inspiratory stridor. A chest X-ray film showed loss of volume and nearly complete radiopacity of the left hemithorax. Arterial blood gas analysis revealed an arterial oxygen partial pressure of 54.8 mmHg, a carbon dioxide partial pressure of 39.8 mmHg, and an oxygen saturation of 84.5 percent on room air. Computed tomographic examination of the thorax showed dilation of the aortic arch and descending aorta, and marked compression of the trachea and the left main bronchus. Examination with a fiberoptic bronchoscope revealed extrinsic compression of the trachea just proximal to the carina. The patient's symptoms stabilized. However, she did not undergo surgery because of her age and because of the size of the aneurysm. She died due to rupture of the aneurysm.     

Human papillomavirus investigation of patients with cervical intraepithelial neoplasia 3, some of whom progressed to invasive cancer

Unstable expansion of the CTG repeats in the 3' untranslated region encoding a member of the protein kinase family in the q13.3 band on chromosome 19 is a mutation specific for myotonic dystrophy. To examine the correlation between clinical expression and CTG trinucleotide repeat length, we carried out Southern blot analysis in a family with myotonic dystrophy. In this pedigree, the expanded CTG repeats were transmitted maternally. The mother had three female children. The mother had about 200 CTG repeats, and the number of repeats for each child was about 800, 1500 and 1600 in birth order. The mother and the patient with 800 repeats were unaware of muscle weakness or myotonia. Symptoms were present from age 3 years in the patient with 1500 repeats and from birth in the one with 1600 repeats. Although the mother menstruated regularly, the patients with 800 and 1500 repeats both menstruated irregularly, and the one with 1600 repeats has never menstruated. The age of onset and severity of the disease were correlated with the size of the expanded repeats. Endocrinological studies revealed that the basal levels of the gonadotropins, PRL and E2 were within normal range, and a pituitary response to LHRH was observed. These data suggest that the amenorrhea and menstrual irregularities were caused by a suprahypophyseal dysfunction. When expanded CTG repeats are transmitted maternally, abnormal products resulting from the metabolic disturbance in the affected mother may harm the fetus in utero. A heterozygous fetus, who has more CTG repeats, may be unable to metabolize the pathologic products sufficiently and therefore may become more severely affected. This may explain the exclusive maternal transmission of congenital myotonic dystrophy.     

Localization of interferon-gamma and Ia-antigen in T cell line-mediated experimental autoimmune encephalomyelitis

This study reports the cellular localization of interferon-gamma (IFN-gamma) and MHC class II antigen (Ia) in the spinal cord of rats with experimental autoimmune encephalomyelitis induced by adoptive transfer of myelin basic protein-specific T cells. Numerous IFN-gamma-positive cells, stained with two different monoclonal antibodies against IFN-gamma, were present from days 3 to 7 after cell transfer. Their number was greatly reduced on day 10. A subpopulation of T cells was IFN-gamma positive. Moreover, a large number of ED1-positive macrophages contained IFN-gamma immunoreactivity. The transient presence of immune cells containing IFN-gamma immunoreactivity in experimental autoimmune encephalomyelitis suggests a pathogenic role of this cytokine in immune-mediated demyelination of the central nervous system.