Heme oxygenase-2 is a hemoprotein and binds heme through heme regulatory motifs that are not involved in heme catalysis

The heme oxygenase (HO) system degrades heme to biliverdin and CO and releases chelated iron. In the primary sequence of the constitutive form, HO-2, there are three potential heme binding sites: two heme regulatory motifs (HRMs) with the absolutely conserved Cys-Pro pair, and a conserved 24-residue heme catalytic pocket with a histidine residue, His151 in rat HO-2. The visible and pyridine hemochromogen spectra suggest that the Escherichia coli expressed purified HO-2 is a hemoprotein. The absorption spectrum, heme fluorescence quenching, and heme titration analysis of the wild-type protein versus those of purified double cysteine mutant (Cys264/Cys281 --> Ala/Ala) suggest a role of the HRMs in heme binding. While the His151 --> Ala mutation inactivates HO-2, Cys264 --> Ala and Cys281 --> Ala mutations individually or together (HO-2 mut) do not decrease HO activity. Also, Pro265 --> Ala or Pro282 --> Ala mutation does not alter HO-2 activity. Northern blot analysis of ptk cells indicates that HO-2 mRNA is not regulated by heme. The findings, together with other salient features of HO-2 and the ability of heme-protein complexes to generate oxygen radicals, are consistent with HO-2, like five other HRM-containing proteins, having a regulatory function in the cell.     

Primary sternal osteomyelitis presenting as a pleural-based mass

Osteomyelitis in uncommon locations can present unusual diagnostic difficulties. A patient with primary sternal osteomyelitis who presented with pain over the right supraclavicular area and a radiologic picture of a pleural-based right upper lung mass is discussed. A triple-phase bone scan was consistent with the diagnosis, and a needle aspiration of the mass revealed a staphylococcal abscess. Percutaneous drainage of the contiguous abscess and a prolonged course of antibiotic therapy cured the infection.     

Predictors of long-term smoking cessation in head and neck cancer patients

Cigarette smoking is a major risk factor for head and neck cancer, and individuals who continue to smoke past diagnosis and treatment are at elevated risk for further disease. In a randomized controlled trial, a state of the art provider-delivered smoking cessation intervention was compared to a usual care advice control condition. The intervention consisted of surgeon- or dentist-delivered advice to stop smoking, a contracted quit date, tailored written materials, and booster advice sessions. Subjects were 186 patients with newly diagnosed first primary squamous cell carcinomas of the upper aerodigestive tract who had smoked cigarettes within the past year. At randomization, 88.2% of subjects were current smokers. At 12-month follow-up, 70.2% of subjects completing the trial (n = 114) were continuous abstainers; among baseline smokers alone the continuous abstinence (CA) rate was 64.6%. The cotinine validation rate at 12 months was 89.6%. Modeling techniques were utilized in order to derive expected CA rates, which included noncompleter subjects (n = 72). The CA rate expected at 1 year for the entire patient population was 64.2%, and for smokers alone the expected CA rate was 59.4%. Logistic regression analysis carried out on baseline smokers identified predictors of 12-month CA status. These included medical treatment, stage of change, age, nicotine dependence, and race. The intervention effect was not significant, although the sign of the effect was positive. Based on these findings, we recommend systematic brief advice to stop smoking for head and neck cancer patients, with a stepped care approach for patients less able to quit.     

Intraocular pressure fluctuations during scleral buckling surgery

PURPOSE: The purposes of this study are to measure real-time intraocular pressure (IOP) during scleral buckling and to determine the effects of elevated IOPs on ocular perfusion. PATIENTS AND METHODS: A standard 4-mm, 20-gauge infusion cannula was inserted through the pars plana, connected to a standard hemodynamic monitoring unit with an electronic pressure transducer, and calibrated. The authors measured real-time IOP in 20 eyes undergoing scleral buckling surgery for primary rhegmatogenous retinal detachments and determined the IOP required to close the central retinal artery. Pressure measurements were read from the monitor videoscreen intraoperatively and from a continuous paper tracing postoperatively. RESULTS: The patients ranged in age from 24 to 88 years (mean, 59.7 years). The highest IOP elevations occurred during scleral depression and cryopexy, ranging up to 210 mmHg (mean, 116 mmHg). Pressures at which the central retinal artery closed ranged from 48 to 110 mmHg (mean, 79.2 mmHg). Manipulations of the globes caused IOPs greater than the central retinal artery perfusion pressures in 13 of the 20 patients. The duration of pressures in excess of the central retinal artery perfusion pressure ranged from 6 to 402 seconds (mean, 118.8 seconds). There were no intraoperative or postoperative complications from the infusion cannula. CONCLUSIONS: Conventional scleral buckling surgery causes wide fluctuations in IOP and may impair ocular perfusion. Additional studies are needed to determine the long-term consequences of these pressure elevations.     

Self-disclosure and coping styles in men with cardiovascular reactivity

The purpose of this study was to investigate self-disclosure, emotion-focused, and problem-focused coping styles among men with borderline hypertension and two groups of normotensive men differentiated by parental hypertension. Because blood pressure reactivity may discriminate between hypertensive and normotensive men, subjects in these three groups were categorized as high or low cardiovascular reactors based on their blood pressure response to a mental arithmetic task. Self-disclosure and coping styles were investigated in relation to status effects within the doctor-patient relationship. Men with exaggerated blood pressure reactivity were less self-disclosive and used fewer emotion-focused coping strategies than men with no blood pressure reactivity. Normotensives with a history of parental hypertension were less self-disclosive than normotensives without a history of parental hypertension.     

Effects of serotonin and the serotonin blocker metergoline on meal patterns and macronutrient selection

Serotonin [5-hydroxytryptamine(5-HT)] in the paraventricular nucleus (PVN) of rats has a suppressive effect on feeding behavior and causes a selective decrease in carbohydrate ingestion, specifically at the onset of the natural (dark) feeding period. Studies conducted here provide further evidence for this phenomena, showing a similar dose-related decrease in carbohydrate ingestion at dark onset after PVN injection of 5-HT or of the agonists, d-norfenfluramine or fluoxetine, which act through endogenous 5-HT. To further characterize the effects of this indoleamine on the macrostructure of feeding, a computer-automated data acquisition system was used to analyze macronutrient feeding patterns in freely feeding animals maintained on the pure diets of protein, carbohydrate, and fat. Results indicate that PVN administration of 5-HT at dark onset decreases intake of the carbohydrate nutrient by decreasing meal size, feeding time, and feeding rate for this nutrient and increasing the satiating effect of carbohydrate. These effects, which occur specifically during the first meal after injection, are opposite those seen after peripheral administration of the 5-HT receptor antagonist, metergoline. This drug stimulates feeding through a selective increase in carbohydrate intake, characterized by an increase in meal size, percent composition, and feeding time for this nutrient and a decrease in the satiety ratio for carbohydrate. These results implicate the serotonergic system in the termination of carbohydrate-rich meals that are prevalent during the early hours of the natural feeding cycle.     

Radiation therapy of giant aggressive keratoacanthomas

BACKGROUND AND DESIGN: Giant aggressive keratoacanthoma is a rare destructive subset of keratoacanthoma that frequently involves the facial region, grows rapidly to a large size, and often recurs after surgical management. The effectiveness of ionizing radiation therapy was examined in a retrospective study involving 16 patients; 14 of the tumors had recurred after surgical therapy. RESULTS: All tumors resolved with satisfactory cosmetic results and without recurrence following a fractionated course of superficial radiation therapy. CONCLUSIONS: Radiation therapy is an effective therapeutic modality for giant aggressive keratoacanthomas.     

Buprenorphine medication versus voucher contingencies in promoting abstinence from opioids and cocaine.

During a 12-week intervention, opioid dependent participants (N = 120) maintained on thrice-a-week (M, W, F) buprenorphine plus therapist and computer-based counseling were randomized to receive: (a) medication contingencies (MC = thrice weekly dosing schedule vs. daily attendance and single-day 50% dose reduction imposed upon submission of an opioid and/or cocaine positive urine sample); (b) voucher contingency (VC = escalating schedule for opioid and/or cocaine negative samples with reset for drug-positive samples); or (c) standard care (SC), with no programmed consequences for urinalysis results. VC resulted in better 12-week retention (85%) compared to MC (58%; p = 0.009), but neither differed from SC (76% retained). After adjusting for baseline differences in employment, and compared to SC, the MC group achieved 1.5 more continuous weeks of combined opioid/cocaine abstinence (p = 0.030), while the VC group had 2 more total weeks of abstinence (p = 0.048). Drug use results suggest that both the interventions were efficacious, with effects primarily in opioid rather than cocaine test results. Findings should be interpreted in light of the greater attrition associated with medication-based contingencies versus the greater monetary costs of voucher-based contingencies. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Test-retest reliability of psychological and neurobehavioral tests self-administered by computer

Adult rat chromaffin cells may proliferate or extend neurites when stimulated by nerve growth factor (NGF) but their response is predominantly proliferative, making them a unique model for studying how mitogenic specificity is achieved. We examined contributions of the NGF receptors trk and p75 and of the major NGF signaling pathways to proliferation versus neurite outgrowth. The type of initial NGF response does not correlate with intensity of immunoreactivity for trk or p75. However, proliferation is initiated at lower NGF concentrations than neurite outgrowth, suggesting that it requires a less intense signal. Mitogenic cooperativity between receptors at low NGF concentrations is suggested by inhibitory effects of p75-blocking antibodies, but responses to trk-agonist antibody indicate that trk activation alone can induce proliferation. NGF-induced phosphorylation of ras-mediated mitogen-activated protein kinases (MAPK) Erk1 and Erk2 is as prolonged in normal chromaffin cells as in PC12 cells, where NGF is neuritogenic. Trk-agonist antibody, which is as mitogenic as NGF but less neuritogenic, causes equally prolonged but less intense ERK phosphorylation. The MAPK kinase(MEK-1) inhibitor PD98059 partially inhibits Erk phosphorylation and does not inhibit chromaffin cell proliferation, while depolarization selectively inhibits proliferation without blocking Erk phosphorylation. Proliferation is markedly reduced by the phosphoinositol-3 (PI-3) kinase inhibitor LY294002 while downregulation of protein kinase C (PKC) causes no change. These findings suggest that low-level, rather than short-duration, stimulation of NGF signaling pathways causes NGF to be mitogenic. Ras-mediated MAPK activation may be more critical in neurite outgrowth than in proliferation and PI-3 kinase may be the major mitogenic determinant.     

Interaction of murine MHC class I molecules with tapasin and TAP enhances peptide loading and involves the heavy chain alpha3 domain

In human cells the association of MHC class I molecules with TAP is thought to be mediated by a third protein termed tapasin. We now show that tapasin is present in murine TAP-class I complexes as well. Furthermore, we demonstrate that a mutant H-2Dd molecule that does not interact with TAP due to a Glu to Lys mutation at residue 222 of the H chain (Dd(E222K)) also fails to bind to tapasin. This finding supports the view that tapasin bridges the association between class I and TAP and implicates residue 222 as a site of contact with tapasin. The inability of Dd(E222K) to interact with tapasin and TAP results in impaired peptide loading within the endoplasmic reticulum. However, significant acquisition of peptides can still be detected as assessed by the decay kinetics of cell surface Dd(E222K) molecules and by the finding that prolonged viral infection accumulates sufficient target structures to stimulate T cells at 50% the level observed with wild-type Dd. Thus, although interaction with tapasin and TAP enhances peptide loading, it is not essential. Finally, a cohort of Dd(E222K) molecules decays more rapidly on the cell surface compared with wild-type Dd molecules but much more slowly than peptide-deficient molecules. This suggests that some of the peptides obtained in the absence of an interaction with tapasin and TAP are suboptimal, suggesting a peptide-editing function for tapasin/TAP in addition to their role in enhancing peptide loading.