University at Buffalo

About: University at Buffalo is a education organization based out in Buffalo, New York, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 33773 authors who have published 63840 publications receiving 2278954 citations. The organization is also known as: UB & State University of New York at Buffalo.

Airway Inflammation and Bronchial Bacterial Colonization in Chronic Obstructive Pulmonary Disease

Abstract: Rationale: Inflammation is now recognized as an integral part of the pathogenesis of chronic obstructive pulmonary disease (COPD). In contrast to the sterile airways of normal lungs, bacterial pathogens are often isolated from the airways in stable COPD. This “colonization” of the tracheobronchial tree, currently believed to be innocuous, could serve as an inflammatory stimulus, independent of current tobacco smoke exposure.Objective: To test the hypothesis that bacterial colonization is associated with airway inflammation in stable COPD.Methods: Bronchoscopy with bronchoalveolar lavage (BAL) was performed in three groups of subjects: 26 ex-smokers with stable COPD (COPD), 20 ex-smokers without COPD (ex-smokers), and 15 healthy nonsmokers (nonsmokers). Quantitative bacterial cultures, cell counts, chemokine, cytokine, proteinase/antiproteinase, and endotoxin levels in the BAL fluid were compared.Results: Potentially pathogenic bacteria were recovered at ⩾ 100 cfu/ml in 34.6% of COPD, 0% of ex-smokers, and...

Accessory Gene Regulator Group II Polymorphism in Methicillin-Resistant Staphylococcus aureus Is Predictive of Failure of Vancomycin Therapy

Abstract: We studied methicillin-resistant Staphylococcus aureus (MRSA) isolates to determine if the group II polymorphism at the accessory gene regulator (agr) locus demonstrated any relationship with the clinical efficacy of vancomycin. One hundred twenty-two MRSA isolates from 87 patients treated with vancomycin were evaluated. Forty-five of 87 patients had no clinical or bacteriological response to vancomycin. Among the 36 clinically evaluable patients with the agr group II polymorphism, 31 had an infection that failed to respond to vancomycin, whereas only 5 had an infection that responded successfully to vancomycin. This finding is of interest in light of our previous findings that glycopeptide-intermediately resistant S. aureus (GISA) and hetero-GISA clinical isolates in the United States and Japan are enriched for the agr group II polymorphism, and it suggests a possible intrinsic survival advantage of some S. aureus clones with this genetic marker under vancomycin selective pressure.

DMT1: A mammalian transporter for multiple metals

Abstract: DMT1 has four names, transports as many as eight metals, may have four or more isoforms and carries out its transport for multiple purposes. This review is a start at sorting out these multiplicities. A G185R mutation results in diminished gastrointestinal iron uptake and decreased endosomal iron exit in microcytic mice and Belgrade rats. Comparison of mutant to normal rodents is one analytical tool. Ectopic expression is another. Antibodies that distinguish the isoforms are also useful. Two mRNA isoforms differ in the 3' UTR: +IRE DMT1 has an IRE (Iron Responsive Element) but -IRE DMT1 lacks this feature. The +/-IRE proteins differ in the distal 18 or 25 amino acid residues after shared identity for the proximal 543 residues. A major function is serving as the apical iron transporter in the lumen of the gut. The +IRE isoform appears to have that role. Another role is endosomal exit of iron. Some evidence indicts the -IRE isoform for this function. In our ectopic expression assay for metal uptake, four metals--Fe2+, Mn2+, Ni2+ and Co2+--respond to the normal DMT1 cDNA but not the G185R mutant. Two metals did not--Cd2+ and Zn2+--and two--Cu2+ and Pb2+--remain to be tested. In competition experiments in the same assay, Cd2+, Cu2+ and Pb2+ inhibit Mn2+ uptake but Zn2+ did not. In rodent mutants, Fe and Mn appear more dependent on DMT1 than Cu and Zn. Experiments based on ectopic expression, specific antibodies that inhibit metal uptake and labeling data indicate that Fe3+ uptake depends on a different pathway in multiple cells. Two isoforms localize differently in a number of cell types. Unexpectedly, the -IRE isoform is in the nuclei of cells with neuronal properties. While the function of -IRE DMT1 in the nucleus is speculative, one may safely infer that this localization identifies new role(s) for this multifunctional transporter. Management of toxic challenges is another function related to metal homeostasis. Airways represent a gateway tissue for metal entry. Preliminary evidence using specific PCR primers and antibodies specific to the two isoforms indicates that -IRE mRNA and protein increase in response to exposure to metal in lungs and in a cell culture model; the +IRE form is unresponsive. Thus the -IRE form could be part of a detoxification system in which +IRE DMT1 does not participate. How does iron status affect other metals' toxicity? In the case of Mn, iron deficiency may enhance cellular responses.

Pet Ownership, but Not ACE Inhibitor Therapy, Blunts Home Blood Pressure Responses to Mental Stress

Abstract: In the present study, we evaluated the effect of a nonevaluative social support intervention (pet ownership) on blood pressure response to mental stress before and during ACE inhibitor therapy. Forty-eight hypertensive individuals participated in an experiment at home and in the physician's office. Participants were randomized to an experimental group with assignment of pet ownership in addition to lisinopril (20 mg/d) or to a control group with only lisinopril (20 mg/d). On each study day, blood pressure, heart rate, and plasma renin activity were recorded at baseline and after each mental stressor (serial subtraction and speech). Before drug therapy, mean responses to mental stress did not differ significantly between experimental and control groups in heart rate (94 [SD 6.8] versus 93 [6.8] bpm), systolic blood pressure (182 [8.0] versus 181 [8.3] mm Hg), diastolic blood pressure (120 [6.6] versus 119 [7.9] mm Hg), or plasma renin activity (9.4 [0.59] versus 9.3 [0.57] ng. mL(-1). h(-1)). Lisinopril therapy lowered resting blood pressure by approximately 35/20 mm Hg in both groups, but responses to mental stress were significantly lower among pet owners relative to those who only received lisinopril (P<0.0001; heart rate 81 [6.3] versus 91 [6.5] bpm, systolic blood pressure 131 [6.8] versus 141 [7.8] mm Hg, diastolic blood pressure 92 [6.3] versus 100 [6.8] mm Hg, and plasma renin activity 13.9 [0.92] versus 16.1 [0.58] ng. mL(-1). h(-1)). We conclude that ACE inhibitor therapy alone lowers resting blood pressure, whereas increased social support through pet ownership lowers blood pressure response to mental stress.