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Biomedical subjects

D Wagner

Publications and source records attributed to D Wagner.

At least 37 records · Page 2Linked to original sources
PubMed2001

Wallerian degeneration of injured axons and synapses is delayed by a Ube4b/Nmnat chimeric gene.

Axons and their synapses distal to an injury undergo rapid Wallerian degeneration, but axons in the C57BL/WldS mouse are protected. The degenerative and protective mechanisms are unknown. We identified the protective gene, which encodes an N-terminal fragment of ubiquitination factor E4B (Ube4b) fused to nicotinamide mononucleotide adenylyltransferase (Nmnat), and showed that it confers a dose-dependent block of Wallerian degeneration. Transected distal axons survived for two weeks, and neuromuscular junctions were also protected. Surprisingly, the Wld protein was located predominantly in the nucleus, indicating an indirect protective mechanism. Nmnat enzyme activity, but not NAD+ content, was increased fourfold in WldS tissues. Thus, axon protection is likely to be mediated by altered ubiquitination or pyridine nucleotide metabolism.

Action Potentials↗
PubMed2001

Prevalence of Campylobacter spp., Escherichia coli, and Salmonella serovars in retail chicken, turkey, pork, and beef from the Greater Washington, D.C., area.

A total of 825 samples of retail raw meats (chicken, turkey, pork, and beef) were examined for the presence of Escherichia coli and Salmonella serovars, and 719 of these samples were also tested for Campylobacter spp. The samples were randomly obtained from 59 stores of four supermarket chains during 107 sampling visits in the Greater Washington, D.C., area from June 1999 to July 2000. The majority (70.7%) of chicken samples (n = 184) were contaminated with Campylobacter, and a large percentage of the stores visited (91%) had Campylobacter-contaminated chickens. Approximately 14% of the 172 turkey samples yielded Campylobacter, whereas fewer pork (1.7%) and beef (0.5%) samples were positive for this pathogen. A total of 722 Campylobacter isolates were obtained from 159 meat samples; 53.6% of these isolates were Campylobacter jejuni, 41.3% were Campylobacter coli, and 5.1% were other species. Of the 212 chicken samples, 82 (38.7%) yielded E. coli, while 19.0% of the beef samples, 16.3% of the pork samples, and 11.9% of the turkey samples were positive for E. coli. However, only 25 (3.0%) of the retail meat samples tested were positive for Salmonella. Significant differences in the bacterial contamination rates were observed for the four supermarket chains. This study revealed that retail raw meats are often contaminated with food-borne pathogens; however, there are marked differences in the prevalence of such pathogens in different meats. Raw retail meats are potential vehicles for transmitting food-borne diseases, and our findings stress the need for increased implementation of hazard analysis of critical control point (HACCP) and consumer food safety education efforts.

Animals↗
PubMed2001

Identification and characterization of integron-mediated antibiotic resistance among Shiga toxin-producing Escherichia coli isolates.

A total of 50 isolates of Shiga toxin-producing Escherichia coli (STEC), including 29 O157:H7 and 21 non-O157 STEC strains, were analyzed for antimicrobial susceptibilities and the presence of class 1 integrons. Seventy-eight (n = 39) percent of the isolates exhibited resistance to two or more antimicrobial classes. Multiple resistance to streptomycin, sulfamethoxazole, and tetracycline was most often observed. Class 1 integrons were identified among nine STEC isolates, including serotypes O157:H7, O111:H11, O111:H8, O111:NM, O103:H2, O45:H2, O26:H11, and O5:NM. The majority of the amplified integron fragments were 1 kb in size with the exception of one E. coli O111:H8 isolate which possessed a 2-kb amplicon. DNA sequence analysis revealed that the integrons identified within the O111:H11, O111:NM, O45:H2, and O26:H11 isolates contained the aadA gene encoding resistance to streptomycin and spectinomycin. Integrons identified among the O157:H7 and O103:H2 isolates also possessed a similar aadA gene. However, DNA sequencing revealed only 86 and 88% homology, respectively. The 2-kb integron of the E. coli O111:H8 isolate contained three genes, dfrXII, aadA2, and a gene of unknown function, orfF, which were 86, 100, and 100% homologous, respectively, to previously reported gene cassettes identified in integrons found in Citrobacter freundii and Klebsiella pneumoniae. Furthermore, integrons identified among the O157:H7 and O111:NM strains were transferable via conjugation to another strain of E. coli O157:H7 and to several strains of Hafnia alvei. To our knowledge, this is the first report of integrons and antibiotic resistance gene cassettes in STEC, in particular E. coli O157:H7.

Animals↗
PubMed2001

Pancreatic phospholipase A2 from the small intestine is a secretin-releasing factor in rats.

A secretin-releasing activity exists in the upper small intestine and pancreatic juice in the rat and the dog. Group I pancreatic phospholipase A2 (PLA2) in canine pancreatic juice and porcine pancreatic PLA2 stimulate the release of secretin from both STC-1 cells and a secretin-producing cell (S cell)-enriched preparation isolated from rat duodenal mucosa. We investigated the distribution and release of pancreatic PLA2-like immunoreactivity in the gastrointestinal tract and the role of PLA2 on the release of secretin and pancreatic exocrine secretion in response to duodenal acidification in anesthetized rats. PLA2-like immunoreactivity was detected in the mucosa throughout the gastrointestinal tract. High concentrations of PLA2 were found in both the small intestine and the pancreas. Duodenal acidification significantly increased the release of PLA2 from the upper small intestine (385% over basal secretion). Intravenous infusion of an anti-PLA2 serum (anti-PLA2) dose-dependently inhibited the release of secretin and pancreatic exocrine secretion in response to duodenal acid perfusion. Preincubation of the concentrate of intestinal acid perfusate (10-fold) from donor rats with the anti-PLA2 significantly suppressed its stimulation of secretin release and pancreatic exocrine secretion in recipient rats. We conclude that pancreatic PLA2 also functions as a secretin-releasing factor in the small intestine that mediates acid-stimulated release of secretin in rats.

Animals↗
PubMed2001

Effect of exercise training on postexercise oxygen uptake kinetics in patients with reduced ventricular function.

BACKGROUND: The time required for oxygen uptake (O(2)) to return to baseline level (recovery kinetics) is prolonged in patients with reduced ventricular function, and the degree to which it is prolonged is related to the severity of heart failure, markers of abnormal ventilation, and prognosis. In the present study, we sought to determine the effect of exercise training on O(2) recovery kinetics in patients with reduced ventricular function. METHODS: Twenty-four male patients with reduced ventricular function after a myocardial infarction were randomized to either a 2-month high-intensity residential exercise training program or to a control group. O(2) kinetics in recovery from maximal exercise were calculated before and after the study period and expressed as the slope of a single exponential relation between O(2) and time during the first 3 min of recovery. RESULTS: Peak O(2) increased significantly in the exercise group (19.4 +/- 3.0 mL/kg/min vs 25.1 +/- 4.7 mL/kg/min, p < 0.05), whereas no change was observed in control subjects. The O(2) half-time in recovery was reduced slightly after the study period in both groups (108.7 +/- 33.1 to 102.1 +/- 50.5 s in the exercise group and 122.3 +/- 68.7 to 107.5 +/- 36.0 s in the control group); neither the change within or between groups was significant. The degree to which O(2) was prolonged in recovery was inversely related to measures of exercise capacity (peak O(2), watts achieved, and exercise time; r = - 0.48 to - 0.57; p < 0.01) and directly related to the peak ventilatory equivalents for oxygen (r = 0.59, p < 0.01) and carbon dioxide (r = 0.57, p < 0.01). CONCLUSION: Two months of high-intensity training did not result in a faster recovery of O(2) in patients with reduced ventricular function. This suggests that adaptations to exercise training manifest themselves only during, but not in, recovery from exercise.

Carbon Dioxide↗
PubMed2000

A Ufd2/D4Cole1e chimeric protein and overexpression of Rbp7 in the slow Wallerian degeneration (WldS) mouse.

Exons of three genes were identified within the 85-kilobase tandem triplication unit of the slow Wallerian degeneration mutant mouse, C57BL/Wld(S). Ubiquitin fusion degradation protein 2 (Ufd2) and a previously undescribed gene, D4Cole1e, span the proximal and distal boundaries of the repeat unit, respectively. They have the same chromosomal orientation and form a chimeric gene when brought together at the boundaries between adjacent repeat units in Wld(S). The chimeric mRNA is abundantly expressed in the nervous system and encodes an in-frame fusion protein consisting of the N-terminal 70 amino acids of Ufd2, the C-terminal 302 amino acids of D4Cole1e, and an aspartic acid formed at the junction. Antisera raised against synthetic peptides detect the expected 43-kDa protein specifically in Wld(S) brain. This expression pattern, together with the previously established role of ubiquitination in axon degeneration, makes the chimeric gene a promising candidate for Wld. The third gene altered by the triplication, Rbp7, is a novel member of the cellular retinoid-binding protein family and is highly expressed in white adipose tissue and mammary gland. The whole gene lies within the repeat unit leading to overexpression of the normal transcript in Wld(S) mice. However, it is undetectable on Northern blots of Wld(S) brain and seems unlikely to be the Wld gene. These data reveal both a candidate gene for Wld and the potential of the Wld(S) mutant for studies of ubiquitin and retinoid metabolism.

Amino Acid Sequence↗
PubMed2000

Sleep and wakefulness in c-fos and fos B gene knockout mice.

G-protein coupled receptor (GPCR) stimulation has been implicated in the regulation of sleep. Upon stimulation of a GPCR an intracellular cascade involving second and third messengers is initiated. The latter include the fos-family of immediate early genes (IEGs). Although there is considerable evidence indicating that IEGs are expressed in response to sleep, the effects of their deletion on sleep is not known. The present study examined sleep-wakefulness in mice lacking the c-fos or fos B genes. Null c-fos mice compared to their wildtype (WT) and heterozygote (het) siblings had more wakefulness and less slow wave sleep (SWS); REM sleep was not affected. The null c-fos mice also had increased delta activity (0.3-4 Hz). In contrast, the null and heterozygote fos B mice had less REM sleep, but the time spent in SWS or wakefulness was not different from their wild-type (WT) siblings. In the null c-fos mice, the increased wakefulness and the reduction in SWS could not be due to a systemic alteration in temperature since the core temperature was similar in all mice. By demonstrating that these IEGs are involved in sleep, we suggest that the deletion of specific genes, even within a family of genes, can have a specific effect on sleep.

Animals↗
PubMed2000

The role of tumor necrosis factor in the pathophysiology of heart failure.

Recent studies have focused their attention on the role of the proinflammatory cytokine tumor necrosis factor (TNF) in the development of heart failure. First recognized as an endotoxin-induced serum factor that caused necrosis of tumors and cachexia, it is now recognized that TNF participates in the pathophysiology of a group of inflammatory diseases including rheumatoid arthritis and Crohn's disease. The normal heart does not express TNF; however, the failing heart produces robust quantities. Furthermore, there is a direct relationship between the level of TNF expression and the severity of disease. In addition, both in vivo and in vitro studies demonstrate that TNF effects cellular and biochemical changes that mirror those seen in patients with congestive heart failure. Furthermore, in animal models, the development of the heart failure phenotype can be abrogated at least in part by anticytokine therapy. Based on information from experimental studies, investigators are now evaluating the clinical efficacy of novel anticytokine and anti-TNF strategies in patients with heart failure; one such strategy is the use of a recombinantly produced chimeric TNF alpha soluble receptor. Thus, in view of the emerging importance of proinflammatory cytokines in the pathogenesis of heart disease, we review the biology of TNF, its role in inflammatory diseases, the effects of TNF on the physiology of the heart and the development of clinical strategies that target the cytokine pathways.

Animals↗
PubMed2000

c-Fos expression in the cholinergic basal forebrain after enforced wakefulness and recovery sleep.

The present study used c-Fos expression to examine cellular activity in cholinergic regions in the basal forebrain (BF) following enforced waking and recovery sleep. Cholinergic cells within the vertical and horizontal limbs of the diagonal band of Broca (VDB and HDB, respectively) showed significantly higher c-Fos immunoreactivity after prolonged waking than after recovery sleep. Cholinergic cells within the medial septal nucleus (MS), however, showed no change in c-Fos expression under these conditions. Consistent with our previous findings, c-Fos immunoreactivity in the ventral lateral preoptic area (VLPO) was increased after 1-2h of recovery sleep compared with enforced waking. These results indicate state-specific effects on transcription and subsequent protein expression in cell populations associated with behavioral state and further show that the HDB, VDB and VLPO are good candidates for the further study of intracellular events associated with sleep and wakefulness.

Animals↗
PubMed2000

[A new technique for laparoscopic placement of the adjustable gastric band (LAP-band) for preventing slippage].

BACKGROUND: Slippage (SP) of the stomach is the most common postoperative complication after laparoscopic adjustable silicone gastric banding (LAS-GB) for morbid obesity. METHODS AND PATIENTS: A randomized prospective study was constructed in order to determine whether laparoscopic placement behind the cardia (RKP) is associated with a lower incidence of postoperative SP and pouch dilation than after a retrogastric placement (RGP) of the LAP band using a common technique. Morbidly obese patients presenting for LASGB were randomized to undergo either an RKP (n = 50) or an RGP (n = 51). RESULTS: There were three postoperative SP and three pouch dilations in the RGP group versus no postoperative complication in the RKP group. CONCLUSIONS: The placement of LAP band by the RKP technique is safe and followed by a lower frequency of postoperative complications than with the RGP technique. Clear anatomical landmarks are a benefit to the education and learning curve of LASGB.

Adolescent↗
PubMed2000

[Family study of patients with aspirin intolerance and rhinosinusitis].

The high prevalence of aspirin intolerance in asthmatics and patients with nasal polyps as well as reports of familial clustering suggest a genetic disposition of this disease. Our study aimed at obtaining further evidence of hereditary factors in this disease. We included 33 unselected patients from 28 families with aspirin intolerance and rhinosinusitis in this study. Controls were recruited from individuals treated in our ENT clinic for diseases other than aspirin intolerance (n = 52). A questionnaire focused on family histories as well as reports on diseases of the upper respiratory tract or allergies. ASS intolerance was verified either by bronchial or nasal provocation tests. We found cases of aspirin intolerance among parents, siblings, and children of ASS intolerant probands. The children of probands had nasal polyps and rhinosinusitis more often than the children of controls. We propose that ASS intolerance with nasal polyps and asthma represents a complex phenotype, with genetic and environmental factors contributing to its manifestation.

Adolescent↗
PubMed2000

Social desirability scores are associated with higher morning cortisol levels in firefighters.

OBJECTIVE: To examine the association of social desirability (SD) responding ("defensiveness") and cortisol levels. METHODS: Marlowe-Crowne SD scores and morning salivary cortisol were measured in firefighters. RESULTS: SD scores were associated with higher cortisol levels (r=.28) in 60 firefighters under age 45, but not in 25 older firefighters (or the combined sample). CONCLUSION: The results are consistent not only with SD scores being an indicator of coarctation of experience as a coping mechanism, but also (at least for younger persons) perhaps a risk factor for the psychobiological dysfunctions associated with chronic elevations of cortisol.

Adaptation, Psychological↗
PubMed2000

Nonsteroidal anti-inflammatory drugs, acetaminophen, cyclooxygenase 2, and fever.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used antipyretic agents that most probably exert their antifever effect by inhibiting cyclooxygenase (COX)-2. Thus, COX-2-selective drugs or null mutation of the COX-2 gene reduce or prevent fever. Acetaminophen is antipyretic and analgesic, as are NSAIDs, but it lacks the anti-inflammatory and anticoagulatory properties of these drugs. This has led to the speculation that a COX variant exists that is inhibitable by acetaminophen. An acetaminophen-inhibitable enzyme is inducible in the mouse J774.2 monocyte cell line. Induction of acetaminophen-inhibitable prostaglandin E(2) synthesis parallels induction of COX-2. Thus, inhibition of pharmacologically distinct COX-2 enzyme activity by acetaminophen may be the mechanism of action of this important antipyretic drug.

Acetaminophen↗
PubMed2000

The impact of long-term acute-care facilities on the outcome and cost of care for patients undergoing prolonged mechanical ventilation.

OBJECTIVES: To compare the 6-month mortality rate of chronically ventilated patients treated either exclusively in a traditional acute-care hospital or transferred during hospitalization to a long-term acute-care facility. To analyze the hospital cost of care and estimate the amount of uncompensated care incurred by acute-care hospitals under the Medicare prospective payment diagnostic related groups system. DESIGN: Retrospective chart review and questionnaire. SETTING: Fifty-four acute-care referral hospitals and 26 longterm acute-care institutions. PATIENTS: A total of 432 ventilated patients selected from 3,266 patients referred but not transferred to a study long-term acute-care facility and 1,702 ventilated patients from 4,174 patients referred and then subsequently transferred to the long-term acute-care facility. Six-month outcomes were determined for the subgroup of patients > or =65 yrs old (279 and 1,340 patients, respectively). Hospital charges were available for 192 of the 279 nontransferred patients who were > or =65 yrs old and 1,332 of the 1,340 transferred patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The 6-month mortality rate was 67.4% for the 279 nontransferred patients and 67.2% for the 1,340 transferred patients. On multiple regression analysis, variables associated with the 6-month mortality rate included initial admitting diagnosis, age, the acute physiology score, and presence of decubitus ulcer. After controlling for these variables, there was no significant difference in 6-month mortality rate, but admission to the long-term acute-care facility was associated with a longer mean survival time. Average total hospital costs for the 192 nontransferred patients was $78,474, and estimated Medicare reimbursement was $62,472, resulting in an average of $16,002 of uncompensated care per patient. Estimated costs for the long-term acute-care facility admissions were $56,825. CONCLUSIONS: Patients undergoing prolonged ventilation have high hospital and 6-month mortality rates, and 6-month outcomes are not significantly different for those transferred to long-term acute-care facilities. These patients generate high costs, and acute-care hospitals are significantly underreimbursed by Medicare for these costs. Acute-care hospitals can reduce the amount of uncompensated care by earlier transfer of appropriate patients to a long-term acute-care facility.

Aged↗
PubMed2000

In vivo microscopic evaluation of the microvascular behavior of FITC-labeled macromolecular MR contrast agents in the hamster skinfold chamber.

RATIONALE AND OBJECTIVES: The extravasation properties of two macromolecular MR imaging contrast media (CM) in relation to structural differences of the terminal vascular bed were investigated to determine whether differentiation between normal (physiological) and tumor (pathological) tissue can be achieved by means of extravasation characteristics. METHODS: Gd-DTPA-polylysine (50 kD, CM1) and Gd-DOTA cascade polymer (Gadomer 17; 20 kD, CM2) were labeled with fluorescein isothiocyanate (FITC) to enable in vivo fluorescence microscopy of the microcirculation. After implantation of a dorsal skinfold chamber and 7 days (range, 6-8) after induction of an amelanotic melanoma (A-Mel-3), 14 male hamsters weighing 85 g (range, 70-95 g) received 200 micromol/kg of CM1 by intravenous injection into the jugular vein. CM2 was similarly investigated after an interval of 24 hours. Fluorescence microscopy was performed in areas of subcutaneous tissue, striated muscle, and tumor tissue. Microscopic images were registered by a charge-coupled-device video camera and transferred to a video system. Distribution intensities of CM were evaluated on a digitally based measurement system. A control investigation was performed with FITC-dextran (150 kD). RESULTS: Gd-DTPA-polylysine showed no extravasation into physiological tissue for the first 10 minutes after injection. After this period, however, the first signs of leakage became apparent. Gd-DOTA cascade polymer was extravasated after 5 minutes into the tumor-free tissue. In tumor capillaries, Gd-DTPA-polylysine could be detected in the extravasal space as well as in physiological tissue after 15 minutes. After injection of Gd-DOTA cascade polymer, direct leakage from tumor capillaries was observed, with a contrast maximum between tumor and surrounding tissue occurring 3 to 5 minutes after CM injection. Good delineation of tumor vascularization from striated muscle and subcutaneous tissue was achieved. CONCLUSIONS: The CM studied showed different microvascular permeation properties. Faster leakage of Gd-DOTA cascade polymer was observed in areas with neoplastic tumor vessels, whereas extravasation in physiological tissue was detected after a period of 5 minutes. Gd-DTPA-polylysine demonstrated nonspecific leakage at later time points.

Animals↗