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PubMed2000

The Brucella abortus Lon functions as a generalized stress response protease and is required for wild-type virulence in BALB/c mice.

The gene encoding a Lon protease homologue has been cloned from Brucella abortus. The putative Brucella abortus Lon shares > 60% amino acid identity with its Escherichia coli counterpart and the recombinant form of this protein restores the capacity of an Escherichia coli lon mutant to resist killing by ultraviolet irradiation and regulate the expression of a cpsB:lacZ fusion to wild-type levels. A sigma32 type promoter was identified upstream of the predicted lon coding region and Northern analysis revealed that transcription of the native Brucella abortus lon increases in response to heat shock and other environmental stresses. ATP-dependent proteolytic activity was also demonstrated for purified recombinant Lon. To evaluate the capacity of the Brucella abortus Lon homologue to function as a stress response protease, the majority of the lon coding region was removed from virulent strain Brucella abortus 2308 via allelic exchange. In contrast to the parent strain, the Brucella abortus lon mutant, designated GR106, was impaired in its capacity to form isolated colonies on solid medium at 41 degrees C and displayed an increased sensitivity to killing by puromycin and H2O2. GR106 also displayed reduced survival in cultured murine macrophages and significant attenuation in BALB/c mice at 1 week post infection compared with the virulent parental strain. Beginning at 2 weeks and continuing for 6 weeks post infection, however, GR106 and 2308 displayed equivalent spleen and liver colonization levels in mice. These findings suggest that the Brucella abortus Lon homologue functions as a stress response protease that is required for wild-type virulence during the initial stages of infection in the mouse model, but is not essential for the establishment and maintenance of chronic infection in this host.

ATP-Dependent Proteases↗
PubMed1994

Disseminated Mycobacterium avium complex disease in patients with AIDS.

Disseminated Mycobacterium avium complex (MAC) infection is a common complication of advanced HIV disease that is associated with significant morbidity. After diagnosis of MAC by recovery of organisms from blood or other normally sterile sites, specific treatment with multiple-drug regimens is appropriate and may reduce morbidity. Multiple-drug regimens with agents active against MAC should be employed to reduce the development of drug resistance. Unfortunately, as most clinical trials of anti-MAC agents have lasted 12 weeks or less and have not compared specific agents, the most effective multiple-drug regimen has not been established. The U.S. Public Health Service Task Force on Prophylaxis and Therapy of MAC recommends treatment of disseminated disease with at least two antimycobacterial agents, one of which should be clarithromycin or possibly azithromycin. Ethambutol, which may have an additive or synergistic effect in combination with other anti-MAC agents, is a reasonable second drug. Other agents with activity include rifampin or rifabutin, clofazimine, ciprofloxacin, or parenteral amikacin. A microbiological response may require up to 2 to 8 weeks. The clinical response generally parallels the microbiological response. Rifabutin, which is licensed for prophylaxis of MAC, reduces the incidence of and delays the time to MAC bacteremia. Individuals at highest risk of MAC bacteremia (i.e., CD4+ cell counts of < 75-100 cells/microliters) had the most benefit from rifabutin prophylaxis. Tuberculosis must be ruled out before rifabutin prophylaxis is initiated. Careful observation without prophylaxis is an acceptable alternative for those who are not able to take rifabutin or alternative agents.

AIDS-Related Opportunistic Infections↗
PubMed1999

Study to evaluate the effectiveness of stress management workshops on response to general and occupational measures of stress.

This study was designed to evaluate the effectiveness of stress management training workshops within Zeneca Pharmaceuticals. The study was of cross-sectional design, comparing groups of workshop attendees and non-attendees. In addition, self-rated well-being scores of attendees were compared with results obtained pre-workshop and 2-3 months after the workshop. Employees participating in the study were drawn from the Manufacturing, Research and Development, Sales and Marketing sites of Zeneca Pharmaceuticals located in Cheshire, United Kingdom. Three hundred and ninety persons who had participated in stress management workshops since 1988 were matched for age, gender and department with an equal number of employees who had not attended stress management workshops. Outcome measures included self-rated well-being (as measured by the 30-question General Health Questionnaire), knowledge of company guidance on the management of stress in staff, and an assessment of coping strategies. Subjects who had not attended a stress management workshop were much more likely to have a poor understanding of the principles of management of stress in staff [odds ratio (OR) = 8.3; 95% confidence interval (CI) = 3.3-21.3] and more likely to have poor coping skills (OR = 2.8; CI = 1.3-6.1). However, mean scores for the two measures were similar in attendees and non-attendees. Self-rating of current well-being was strongly associated with the life-events score, but not related to workshop attendance. The study indicates that stress management training workshops reduce the prevalence of employees with a poor understanding of the principles of the management of stress in staff and with poor coping strategies. An improvement in the self-rated well-being observed shortly after the workshop was not sustained.

Adaptation, Psychological↗
PubMed1995

General stress response to conventional and laparoscopic cholecystectomy.

OBJECTIVE: In many retrospective and prospective observational studies, laparoscopic cholecystectomy (LC) compares favorably with conventional cholecystectomy (CC), with respect to length of hospital stay, postoperative pain, and pulmonary function, indicating a diminished operative trauma. Comparison of laboratory findings (stress hormones, blood glucose, interleukins) are a possibility to objectify stress and tissue trauma of laparoscopic and conventional cholecystectomy. SUMMARY BACKGROUND DATA: Major body injury, surgical or accidental, evokes reproducible hormonal and immunologic responses. The magnitude of many of these changes essentially is proportional to the extent of the injury. METHODS: In a prospective study, biochemical stress parameters were measured in the blood of patients undergoing elective cholecystectomy because of symptomatic cholecystolithiasis. Patients with acute cholecystitis, pancreatitis, choledocholithiasis, or malignant disease were excluded. Values from 40 patients after LC and from 18 patients after CC were compared. Both groups had similar patient characteristics, baseline values, and perioperative care, except for deeper anesthesia during CC. RESULTS: On postoperative day 1, epinephrine (p = 0,05), norepinephrine (p = 0.02), and glucose (p = 0.02) responses were higher after CC. Two days postoperatively, norepinephrine remained higher after CC (p < 0.01). Interleukin-1 beta responses were higher during (p < 0.01) and 6 hours after CC (p = 0.03). Interleukin-6 responses were higher 6 hours (p = 0.03), 1 day (p = 0.02), and 2 days (p < 0.01) after CC. CONCLUSIONS: The results show significant lower values of intraoperatively and postoperatively measured epinephrine, norepinephrine, interleukin-1 beta, and interleukin-6 in patients with laparoscopic cholecystectomy, indicating a minor stress response and tissue trauma in this group of patients. The results correspond to the favorable results of most other trials evaluating clinical aspects of laparoscopic cholecystectomy.

Adult↗
PubMed1997

Evidence for Chewing Insect-Specific Molecular Events Distinct from a General Wound Response in Leaves.

The timing of transcript accumulation of several wound-induced genes is different in insect-damaged and mechanically damaged leaves. Transcripts for the proteinase inhibitor II and 3-hydroxy-3-methylglutaryl-coenzyme A reductase genes accumulate more rapidly in potato (Solanum tuberosum L.) leaves chewed on by caterpillars than in leaves damaged mechanically. The timing of maximum transcript accumulation was not affected by the degree of damage inflicted by the insect larvae. When applied to a mechanical wound site, regurgitant isolated from Manduca sexta larvae causes transcript accumulation profiles to shift to parallel those in insect-damaged tissue. Whether obtained from larvae fed either potato leaves or a nonplant diet, insect regurgitant fed through the petiole of detached leaves also induces accumulation of these transcripts. The transcript accumulation-inducing activity of regurgitant is enhanced by heating at 100[deg]C. Our data suggest that a heat-stable, insect-derived elicitor functions to induce the rapid accumulation of transcripts that may be involved in plant defense against herbivores. Distinct signal transduction pathways that can distinguish between insect damage and abiotic damage might therefore exist in plants.

Journal Article↗