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Biomedical subjects

J A Johnson

Publications and source records attributed to J A Johnson.

At least 37 records · Page 2Linked to original sources
PubMed2003

Roles of superoxide, peroxynitrite, and protein kinase C in the development of tolerance to nitroglycerin.

A current hypothesis states that tolerance to nitroglycerin (GTN) involves increased formation of superoxide (O2*-). Studies showing that inhibitors of protein kinase C (PKC) prevent tolerance to GTN suggest the involvement of PKC activation, which can also increase O2*-. We examined the roles of O2*-, peroxynitrite (ONOO-), and PKC activation in GTN tolerance. Pre-exposure of rat aortic rings to GTN (5 x 10(-4) M) for 2 h caused tolerance to the vasodilating effect of GTN, as evidenced by a substantial rightward shift of GTN concentration-relaxation curves. This shift was reduced by treatment of the rings with the antioxidants uric acid, vitamin C, or tempol or the PKC inhibitor chelerythrine. We also found that O2*- generation via xanthine/xanthine oxidase in the bath induced tolerance to GTN. However, responses to nitroprusside were not affected. In vivo tolerance produced in rats by 3-day i.v. infusion of GTN was also almost completely prevented by coinfusion of tempol. In bovine aortic endothelial cells (EC), addition of GTN produced a marked increase in tyrosine nitrosylation, indicating increased ONOO- formation. This action was blocked by prior treatment with uric acid, superoxide dismutase, NG-nitro-L-arginine methyl ester, or chelerythrine. We also demonstrated that GTN translocates the alpha- and epsilonPKC isoforms in EC. However, PKCzeta was not affected by GTN treatment. In conclusion, tolerance to GTN involves enhanced production of O2*- and ONOO- and activation of NO synthase. Furthermore, sustained activation of alpha- and epsilonPKC isozymes in EC by GTN may play a role in development of tolerance.

Animals↗
PubMed2003

Kinematics of ulnar head arthroplasty.

This in vitro study evaluated the performance of an ulnar head replacement. A joint simulator was employed that produced active forearm rotation in cadaveric specimens, with motion measured using an electromagnetic tracking system. The kinematics of the intact forearm were compared with a partial ulnar head replacement and a full replacement (with and without soft-tissue reconstruction) and a full excision of the ulnar head. There were no differences between intact kinematics and those following prosthetic reconstruction. However, ulnar head excision produced distal radioulnar joint instability in the form of radioulnar convergence and increased anteroposterior translations.

Arthroplasty↗
PubMed2003

Assessing risks for a pre-emergent pathogen: virginiamycin use and the emergence of streptogramin resistance in Enterococcus faecium.

Vancomycin-resistant enterococci (VRE) are an important cause of hospital-acquired infections and an emerging infectious disease. VRE infections were resistant to standard antibiotics until quinupristin/dalfopristin (QD), a streptogramin antibiotic, was approved in 1999 for the treatment of vancomycin-resistant Enterococcus faecium infections in people. After that decision, the practice of using virginiamycin in agriculture for animal growth promotion came under intense scrutiny. Virginiamycin, another streptogramin, threatens the efficacy of QD in medicine because streptogramin resistance in enterococci associated with food animals may be transferred to E faecium in hospitalised patients. Policy makers face an unavoidable conundrum when assessing risks for pre-emergent pathogens; good policies that prevent or delay adverse outcomes may leave little evidence that they had an effect. To provide a sound basis for policy, we have reviewed the epidemiology of E faecium and streptogramin resistance and present qualitative results from mathematical models. These models are based on simple assumptions consistent with evidence, and they establish reasonable expectations about the population-genetic and population-dynamic processes underlying the emergence of streptogramin-resistant E faecium (SREF). Using the model, we have identified critical aspects of SREF emergence. We conclude that the emergence of SREF is likely to be the result of an interaction between QD use in medicine and the long-term use of virginiamycin for animal growth promotion. Virginiamycin use has created a credible threat to the efficacy of QD by increasing the mobility and frequency of high-level resistance genes. The potential effects are greatest for intermediate rates of human-to-human transmission (R0 approximately equal 1).

Anti-Bacterial Agents↗
PubMed2003

Tensile strength of healing peripheral nerves.

Although the time required for a nerve to gain sufficient strength to withstand normal physiologic forces of joint motion is unknown, typically nerve repairs are protected up to 3 weeks postoperatively. The authors investigated the mechanical strength of a nerve repair as a function of time. Fifty adult Sprague-Dawley rats underwent sciatic nerve division and repair, and were sacrificed in groups of 10 at 0, 1, 2, 4, and 8 weeks. Repaired nerves were then mechanically loaded at 5 mm/min to failure. Gapping across the repair site was captured on high-resolution video. The contralateral sciatic nerve served as a control. A significant increase in tensile strength was gained between 0 and 1 week and between 2 and 4 weeks. Healing nerves achieved 63 percent of the strength of the control by 8 weeks. Controls showed no gain in strength over the testing period. Gapping occurred at lower forces at all time increments. From 0 to 1 week, a significant increase in load necessary to produce gapping was found, which did not increase significantly again until 8 weeks. These results may have implications for postoperative rehabilitation protocols in patients with nerve injuries.

Animals↗
PubMed2003

Thermal death kinetics of fifth-instar Plodia interpunctella (Lepidoptera: Pyralidae).

Heat treatments have been suggested as alternatives to chemical fumigants for control of postharvest insects in dried fruits and nuts. Conventional forced hot air treatments heat product too slowly to be practical, but radio frequency treatments are capable of more rapid product heating. While developing radio frequency heat treatments for dried fruits and nuts, the heat tolerance of nondiapausing and diapausing fifth-instar larvae of the Indianmeal moth, Plodia interpunctella (Hübner), was determined using a heating block system developed by Washington State University. Both a 0.5th order kinetic model and a classical empirical model were used to estimate lethal exposure times for temperatures of 44-52 degrees C for nondiapausing fifth-instar larvae. We obtained 95% mortality at exposures suitable for practical radio frequency treatments (< or = 5 min) with temperatures of 50 and 52 degrees C. Diapausing larvae were significantly more tolerant than nondiapausing larvae at the lowest treatment temperature and shortest exposure, but differences were not significant at more extreme temperature-time combinations. Previous studies showed that fifth-instar larvae of the navel orangeworm, Amyelois transitella (Walker), were more heat tolerant than either diapausing or nondiapausing Indianmeal moth larvae. Consequently, efficacious treatments for navel orangeworm would also control Indianmeal moth.

Animals↗
PubMed2003

Use of commercial freezers to control cowpea weevil, Callosobruchus maculatus (Coleoptera: Bruchidae), in organic garbanzo beans.

One California processor of organic garbanzo beans (Cicer arietinum L.), unable to use chemical fumigants, relies on 30-d storage at -18 degrees C to disinfest product of the cowpea weevil, Callosobruchus maculatus (F). To determine whether the storage period may be shortened, the most cold-tolerant life stage of the cowpea weevil was identified. Laboratory studies showed that the egg stage was most tolerant to -18 degrees C and that adults were most susceptible. To examine the efficacy of cold storage disinfestation, bags of black-eyed peas, Vigna unguiculata (L.) Walp., infested with cowpea weevil eggs were buried within garbanzo bean bins placed in a commercial cold storage facility kept at approximately -18 degrees C and removed after 7, 14, and 21 d. Survival was highest in eggs located at the center of the bins and coincided with the slowest cooling rate. Although temperatures within the bins did not reach -18 degrees C until after 14-19 d, egg mortality was estimated to be >98% after just 7 d of exposure. Complete mortality of eggs occurred after 14 d of cold storage. A 2-wk treatment regimen may be sufficient for control of cowpea weevil in organic legumes.

Animals↗
PubMed2003

Quality of life in patients treated with hemodialysis or peritoneal dialysis: what are the important determinants?

BACKGROUND: Patients with end-stage renal disease (ESRD) have significant impairments in health-related quality of life (HRQOL). In part, this is due to the intrusiveness of the treatment (hemodialysis or peritoneal dialysis) that is required. It is unclear whether hemodialysis or peritoneal dialysis is associated with a higher HRQOL. METHODS: 192 prevalent patients who self-selected treatment with hemodialysis (either in-center, satellite or home/self-care hemodialysis) or peritoneal dialysis were studied to determine whether treatment with hemodialysis or peritoneal dialysis is associated with a higher HRQOL. Demographic, laboratory and clinical information (including the presence of comorbid conditions using the Charlson comorbidity index) was assessed at baseline. The outcome of interest was HRQOL, which was measured using the Kidney Disease Quality of Life-Short Form (KDQOL-SF), the Short-Form 36 (SF-36) and the EuroQol EQ-5D at baseline and after 6 and 12 months of follow-up. RESULTS: There was no significant difference in HRQOL scores for the SF-36, the EQ-5D and for 9 of 11 KDQOL dimensions for patients treated with hemodialysis or peritoneal dialysis at baseline. As expected, HRQOL was significantly lower for patients who had more comorbid disease, required assistance with their daily care, and for patients with less than a grade 12 education. After controlling for the effect of other important variables, HRQOL (as measured by the EQ-5D visual analog or index scores) did not differ between hemodialysis and peritoneal dialysis patients. HRQOL was stable over time, both for patients who started on hemodialysis or peritoneal dialysis. CONCLUSIONS: There is no significant difference in HRQOL for prevalent ESRD patients treated with hemodialysis or peritoneal dialysis. It will be important to determine if this finding holds true for incident patients treated with hemodialysis or peritoneal dialysis.

Female↗
PubMed2002

Activation of the antioxidant response element in primary cortical neuronal cultures derived from transgenic reporter mice.

Many phase II protective genes contain a cis -acting enhancer region known as the antioxidant response element (ARE). Increased expression of these genes contributes to the protection of cells from oxidative stress. Transgenic reporter mice were created that carry in their genome the core ARE coupled to the human placental alkaline phosphatase (hPAP) reporter gene. Primary cortical cultures derived from these mice were treated with tBHQ resulting in a dose-dependent increase in hPAP activity. Histochemical staining for hPAP activity was observed in both glia and neurons from tBHQ-treated cultures. The tBHQ-mediated increase in hPAP was not affected by the antioxidant glutathione monoethyl ester (GSHEE), whereas the increase in hPAP following DEM treatment was completely blocked by GSHEE. Pre-treatment of cultures with the PI3-kinase inhibitor LY 294002 demonstrated a dose-dependent decrease in tBHQ-induced hPAP activity. In addition, the tBHQ-mediated expression of ARE-driven genes in primary cortical cultures was blocked by LY 294002. Interestingly, basal expression of Nrf2 was also inhibited by LY 294002. We theorize that increased levels of genes controlled by the ARE are important for cellular protection against oxidative stress. These ARE-hPAP transgenic mice will be an important in vivo model for testing our hypothesis.

Alkaline Phosphatase↗
PubMed2002

Integration of nonchemical treatments for control of postharvest pyralid moths (Lepidoptera: Pyralidae) in almonds and raisins.

We propose a treatment strategy combining an initial disinfestation treatment with one of three protective treatments as an alternative for chemical fumigation of almonds and raisins for control of postharvest insect populations. Initial disinfestation treatments using low oxygen controlled atmosphere (0.4% O2) were designed to disinfest product of field populations of pyralid moths; navel orangeworm, Amyelois transitella (Walker), in almonds and raisin moth, Cadra figulilella (Gregson), in raisins. The protective treatments were cold storage (10 degrees C), controlled atmosphere (5% O2) storage, and application of the Indianmeal moth granulosis virus, and were designed to prevent establishment of Indianmeal moth, Plodia interpunctella (Hübner). The initial disinfestation treatment was effective against laboratory populations of navel orangeworm and raisin moth. Efficacy of protective treatments was determined by exposure of commodities to laboratory Indianmeal moth populations at levels far higher than those found in commercial storage facilities. All three protective treatments prevented development of damaging Indianmeal moth populations as measured by pheromone trap catches and evaluation of product samples. Quality analysis by commercial laboratories showed that overall product quality for all protective treatments was maintained at levels acceptable by industry standards.

Animals↗
PubMed2002

Gamma probe-confirmed laparoscopic accessory splenectomy.

The simultaneous occurrence of idiopathic thrombocytopenic purpura (ITP) and Hodgkin's disease in the same patient is uncommon. There have been only a limited number of reported cases of newly diagnosed ITP following Hodgkin's disease. Even more uncommon is the development of ITP after splenectomy for Hodgkin's disease. Of the reported cases of ITP following splenectomy for Hodgkin's disease, all have been successfully treated with medical therapy. We report an unusual case of an accessory spleen causing ITP in a patient who had undergone a splenectomy for Hodgkin's disease 10 years earlier. The patient underwent hand-held gamma-probe-assisted laparoscopic accessory splenectomy.

Adult↗
PubMed2001

Ring-opening and meso substitution from the reaction of cyanide ion with zinc verdohemes.

The reactivity of zinc verdoheme, [Zn(II)(OEOP)](O(2)CCH(3)) where OEOP is the monoanion of octaethyl-5-oxaporphyrin, with cyanide ion has been shown to be a complex process that involves not only the expected ring-opening of the macrocycle, as occurs with other nucleophiles (methoxide, methanethiolate, dimethylamide), but also substitution at one or two of the meso positions. The ring-opened products have been subjected to crystallographic study. The structures of mu-H(2)O-[Zn(II)(OEB-10,19-(CN)(2))](2) and mu-H(2)O-[(Zn(II)(OEB-10,15,19-(CN)(3))](2) both consist of two helical tetrapyrrole subunits that are coordinated to a zinc ion through four Zn-N bonds. The two zinc ions are coordinated to a bridging water molecule that is also hydrogen bonded to a lactam oxygen atom at one end of each tetrapyrrole subunit. Thus the chiral sense of one helical Zn(II)(OEB-10,19-(CN)(2)) portion is transmitted to the other Zn(II)(OEB-10,19-(CN)(2)) unit and the resulting binuclear unit is chiral. In contrast Co(II)(OEB-15,19-(CN)(2)), which was obtained by the insertion of Co(II) into the free ligand, is monomeric with a four-coordinate cobalt ion. A series of DFT geometry optimization calculations were performed on zinc complexes of 5-oxaporphyrins (verdoheme), verdins (bilindione), 4-cyano-5-oxaporphyrins, and 19-cyanoverdins in an effort to gain insights to the features of these complexes and the reactions that lead to meso-cyano-substituted cyanoverdins.

Ascorbic Acid↗
PubMed2001

Synthesis and biological activity of novel epothilone aziridines.

[reaction: see text]. A series of 12alpha,13alpha-aziridinyl epothilone derivatives were synthesized in an efficient manner from epothilone A. The final semisynthetic route involves a formal double-inversion of stereochemistry at both the C12 and C13 positions. All aziridine analogues were tested for effects on tubulin binding polymerization and cytotoxicity. The results indicate that the aziridine moiety is a viable isosteric replacement for the epoxide in the case of epothilones.

Antineoplastic Agents↗
PubMed2001

The effect of gut metabolism on tacrolimus bioavailability in renal transplant recipients.

BACKGROUND: Tacrolimus, a substrate of CYP3A, has low and variable bioavailability similar to cyclosporine. Co-administration of ketoconazole, potent inhibitor of gut and hepatic CYP3A, has been shown to increase tacrolimus bioavailability in healthy volunteers. The purpose of this study is to assess the role of gut metabolism in the overall bioavailability of tacrolimus in a renal transplant population. METHODS: We prospectively studied 19 adult renal transplant recipients who were receiving tacrolimus as part of a quadruple, sequential immunosuppression regimen. Each patient received tacrolimus (4-hr intravenous dose of 0.04 mg/kg between postoperative days 2 and 4). Whole blood samples were collected over 24 hr. After a 24-hr washout period, a single oral dose of ketoconazole (400 mg) was administered followed by the same intravenous dose of tacrolimus, and subsequent samples were obtained. Steady state oral pharmacokinetic profiles were obtained between 1 and 3 months after transplant while patients were receiving twice daily dosing of tacrolimus to maintain whole blood levels between 10 and 20 ng/ml. Two days later, 400 mg of ketoconazole was administered orally 2 hr before to the morning dose. Whole blood samples were collected over 12 hr. RESULTS: In the absence of ketoconazole, 8.0% of the tacrolimus dose underwent first pass metabolism (E(H)), whereas in the presence of ketoconazole, first pass metabolism was 6.2% (P=0.01). Based on this difference in first pass metabolism, an increase of 2% in bioavailability is expected, but an increase of 47% is observed (P=0.001). CONCLUSIONS: This indicates that the gut metabolism of tacrolimus is extensive and contributes significantly to its bioavailability.

Adult↗
PubMed2001

Phosphatidylinositol 3-kinase, not extracellular signal-regulated kinase, regulates activation of the antioxidant-responsive element in IMR-32 human neuroblastoma cells.

The antioxidant-responsive element (ARE) plays an important role in the induction of phase II detoxifying enzymes including NADPH:quinone oxidoreductase (NQO1). We report herein that activation of the human NQO1-ARE (hNQO1-ARE) by tert-butylhydroquinone (tBHQ) is mediated by phosphatidylinositol 3-kinase (PI3-kinase), not extracellular signal-regulated kinase (Erk1/2), in IMR-32 human neuroblastoma cells. Treatment with tBHQ significantly increased NQO1 protein without activation of Erk1/2. In addition, PD 98059 (a selective mitogen-activated kinase/Erk kinase inhibitor) did not inhibit hNQO1-ARE-luciferase expression or NQO1 protein induction by tBHQ. Pretreatment with LY 294002 (a selective PI3-kinase inhibitor), however, inhibited both hNQO1-ARE-luciferase expression and endogenous NQO1 protein induction. In support of a role for PI3-kinase in ARE activation we show that: 1) transfection of IMR-32 cells with constitutively active PI3-kinase selectively activated the ARE in a dose-dependent manner that was completely inhibited by treatment with LY 294002; 2) pretreatment of cells with the PI3-kinase inhibitors, LY 294002 and wortmannin, significantly decreased NF-E2-related factor 2 (Nrf2) nuclear translocation induced by tBHQ; and 3) ARE activation by constitutively active PI3-kinase was blocked completely by dominant negative Nrf2. Taken together, these data clearly show that ARE activation by tBHQ depends on PI3-kinase, which lies upstream of Nrf2.

Antioxidants↗
PubMed2001

Invasive group B streptococcal disease in Maryland nursing home residents.

Between 1991 and 1995, among 999 nonpregnant adult Maryland residents with group B Streptococcus (GBS) isolated from a normally sterile site, 84 resided in nursing homes (NHs). The age-adjusted annual incidence of GBS infection (per 100,000 population) among those > or = 65 years old was 72.3 for NH residents and 17.5 for community residents (relative risk, 4.1; P < 0.001). Thirty-four case patients resided in 11 NHs with > or = 2 cases; 1 NH had 8 case patients within 22 months. Six of 8 case patients from 3 NHs had serotype V GBS. Molecular subtyping of several isolates identified 2 case patients in 1 NH with identical subtype patterns. NH residents have a markedly higher incidence of invasive GBS than do community residents > or = 65 years old and may serve as a target group for immunization when GBS vaccines become available. Further evaluation of intra-NH transmission of GBS is warranted.

Aged↗
PubMed2001

Nrf2-dependent activation of the antioxidant responsive element by tert-butylhydroquinone is independent of oxidative stress in IMR-32 human neuroblastoma cells.

The antioxidant responsive element (ARE) is a cis-acting regulatory element located in the 5'-flanking region of several genes encoding phase II detoxification enzymes, including NAD(P)H:quinone oxidoreductase (NQO1). We report here that activation of the NQO1 ARE by tert-butylhydroquinone (tBHQ) is dependent on Nrf2 and not oxidative stress in IMR-32 human neuroblastoma cells. Overexpression of wild-type Nrf2 activated ARE in a dose-dependent manner, and ARE activation by tBHQ or diethyl maleate (DEM) was inhibited by dominant/negative Nrf2 not by dominant/negative c-Jun. According to our observation, the palindromic sequence (5' to the core) and the GC box in the ARE core sequence are essential for maximal inducibility by tBHQ or DEM. Overexpression of Nrf2 selectively activated wild-type ARE up to 24 h. In addition, a dramatic nuclear translocation of Nrf2 by tBHQ supports a role for Nrf2 in ARE activation. Although oxidative stress is hypothesized to be a major driving force for ARE activation, pretreatment of antioxidant or antioxidant enzyme did not block tBHQ-mediated ARE activation. In contrast, ARE activation by DEM was inhibited by antioxidants or catalase. These results suggest that ARE activation signals from tBHQ and DEM converge at Nrf2 transcription factor through independent mechanisms.

Antioxidants↗