Search PubMed⌕ Search

Biomedical subjects

S Gordon

Publications and source records attributed to S Gordon.

At least 163 records · Page 9Linked to original sources
PubMed1997

Distinct stress-inducible and developmentally regulated heat shock transcription factors in Xenopus oocytes.

The presence of a maternal pool of heat shock factor (HSF) in Xenopus oocytes has been suggested by two lines of evidence from previous studies. First, heat shock response element (HSE)-binding activity is induced in heat-shocked eggs and embryos prior to expression of zygotic HSF. Second, expression from microinjected heat shock protein promoters in oocytes is induced upon heat shock. To date, however, endogenous oocyte HSF molecules have not been detected, nor has induction of HSE-binding activity been directly demonstrated. Here we report the detection of distinct stress-inducible and developmentally regulated HSE-binding activities of endogenous oocyte factors. Exposure of defolliculated oocytes to heat, cadmium, and arsenite resulted in the formation of an HSE-specific complex detectable by gel mobility shift assay. Induction of HSE-binding activity by each of these stressors corresponded to increased expression from a microinjected hsp70 promoter. The stress-inducible HSE-binding complex was recognized by antiserum against mammalian HSF1, but not by HSF2 antiserum, suggesting that a Xenopus homologue of HSF1 is the major component of this activity. The HSE-binding activity of HSF1 was induced by stress treatments of stage I through VI oocytes, an indication that it is responsive to stress throughout oogenesis. During recovery from heat shock, the HSF1-HSE complex rapidly declined to control levels, but was induced for prolonged periods in oocytes exposed to continuous stress, a pattern unlike the transient activation previously observed in fertilized eggs or embryos. The kinetics of HSF1 activation in oocytes suggests that a key protein(s) regulating attenuation of the stress response is present at exceedingly low levels or is somehow modified during preembryonic development. We also detected an unusual constitutive HSE-binding complex in unstressed stage I and II oocytes, but not in later stage oocytes, eggs, developing embryos, or A6 cells. This constitutive complex was unaffected by heat or chemical treatments and was not recognized by either HSF1 or HSF2 antiserum. Appearance of the constitutive HSE-binding activity during oogenesis corresponded closely with peak levels of hsp70 mRNA detected by Northern blot analysis of RNA from staged oocytes. We suggest that the constitutive HSE-binding activity in early oocytes is formed by a unique developmentally regulated heat shock factor that may play a role in the expression of heat shock proteins during early stages of oogenesis.

Animals↗
PubMed1997

Aspergillus in cytology specimens: a review of 45 specimens from 36 patients.

OBJECTIVE: To assess the clinical significance associated with the identification of fungal elements consistent with Aspergillus in cytology specimens. MATERIALS AND METHODS: For all cytology specimens with reported fungal elements consistent with Aspergillus, reported over a 9 yr and 8 mo period at The Cleveland Clinic Foundation, the patient's medical charts were reviewed with particular attention to underlying disease, presentation, treatment, and clinical course. Cytology results were compared with available microbiologic cultures and tissue specimens in all of the patients. RESULTS: Forty-five cytology specimens with Aspergillus fungal forms, from 36 patients, were identified. Twenty-six patients had concurrent specimens sent for culture in whom II grew Aspergillus species (10 Aspergillus fumigatus), eight grew organisms other than Aspergillus, and seven were no growth. A total of 16 patients (44%) were treated with antifungal treatment (Amphotericin B). Treatment with Amphotericin B was significantly associated with a concurrent growth of Aspergillus species (9/11 patients with Aspergillus culture positive vs. 7/25 patients without a positive culture for Aspergillus, P value = 0.004 (ODDS ratio = 11, 95% confidence interval:#1.6-104, 2-tailed Fisher exact test.) CONCLUSIONS: The presence of fungal forms consistent with Aspergillus in cytology specimens is neither specific nor sensitive for significant infection due to Aspergillus. Treatment with Amphotericin B is more likely to be instituted when a concurrent clinical specimen grows Aspergillus species in culture.

Adult↗
PubMed1997

IL-13 acts on macrophages to block the completion of reverse transcription, inhibit virus production, and reduce virus infectivity.

An understanding of the immune suppression of HIV-1 replication in macrophages continues to be a major goal of AIDS research due to the central role this cell type has in AIDS pathogenesis. We have previously discussed the potential clinical benefits of the anti-inflammatory cytokine interleukin-13 (IL-13), which, unlike IL-4 or IL-10, had limited effects on T cell functions. In this report are extend our observations on the effects of IL-13 on HIV-1 replication in monocyte-derived macrophages (MDM) and show redundancy with IL-4, IL-13 or IL-4 have similar effects on HIV-1 replication in MDM when added at different times after infection, with the ability to decrease infection virus release when added for up to 7 days after infection. Removal of IL-13 from MDM revealed a reduction of infection by 16- to 81-fold based on the absence of viral re-emergence from lower multiplicity of infection (m.o.i.). The reduction of HIV-1 infectivity in MDM caused by IL-13 was further characterized by studies on the formation of viral DNA over a range of m.o.i. IL-13 increased the formation of LTR DNA at the lowest m.o.i. of 0.007 while concurrently inhibiting the formation of gag DNA, a later reverse transcription product, at the highest m.o.i. tested, 0.62. Overall, our data indicate that IL-13 can act on macrophages before and after HIV-1 infection by blocking the completion of reverse transcription, decreasing virus production, and reducing the infectivity of the progeny virions.

Cell Differentiation↗
PubMed1997

Pulmonary artery band migration producing endobronchial obstruction.

Pulmonary artery banding is used in infants to temporarily control excessive pulmonary blood flow. There are reports of band migration including intact bands eroding through the pulmonary artery. The patient presented here had bronchiectasis and eventual destruction of his right middle and lower lobes 5 years after pulmonary artery banding and subsequent definitive cardiac corrective surgery. After undergoing a right middle and lower lobectomy, recurring postoperative respiratory distress prompted repeat bronchoscopy where the original pulmonary artery band was identified and removed. It is hypothesized that this band migrated through the pulmonary artery and into the tracheobronchial tree where it led to obstruction and subsequent destruction of the right middle and lower lobes. Awareness of this potential complication is important for pediatric surgeons who so often care for patients with a past history of cardiac surgery.

Airway Obstruction↗
PubMed1997

Early bloodstream infection after cardiopulmonary bypass: frequency rate, risk factors, and implications.

OBJECTIVE: To determine the incidence, predisposing factors, and outcome of early bloodstream infection after cardiopulmonary bypass. DESIGN: A case control study. SETTING: A 54-bed cardiac surgical intensive care in a tertiary referral center. PATIENTS: Patients from a 30-month period with preoperative hospital stay of <48 hrs and subsequent bloodstream infection within 96 hrs of cardiopulmonary bypass were included in a case group. The control group consisted of patients who had cardiac surgery on the same day as the case group. MEASUREMENTS AND MAIN RESULTS: Patient demographics, history of comorbidity, preoperative laboratory testing, details of surgery, transfusion requirement, inotropic infusions, hemodynamics, and arterial blood gases on admission to intensive care were compared in the two groups. Measures of outcome were duration of mechanical ventilation and intensive care stay, serum creatinine on the first postoperative day, highest creatinine and bilirubin concentrations, and hospital mortality. During the study period, 7,928 patients had cardiac surgery. Sixteen (0.2%) patients had early bloodstream infection; the control group consisted of 95 patients. Thirteen of the patients with bloodstream infection had Gram-negative bacilli on blood culture, two had Candida species, and two had Gram-positive bacteria. On multivariate logistic regression analysis, greater prevalence of preoperative pulmonary hypertension (odds ratio 9; 95% confidence interval 2 to 41.8; p = .004), diabetes (odds ratio 4.6; 95% confidence interval 1.4 to 15.8; p = .01), number of blood products transfused (odds ratio 1.09; 95% confidence interval 1.04 to 1.17; p = .005), and infusion of inotropes (odds ratio 4.7; 95% confidence interval 1.3 to 16.4; p = .02) or vasopressors (odds ratio 4.1; 95% confidence interval 1.3 to 15.6; p = .02) were associated with postoperative bloodstream infection. Early bloodstream infection was associated with significantly prolonged duration of mechanical ventilation (117.2 +/- 21.5 vs. 18 +/- 8.8 hrs; p = .0001), intensive care stay (213 +/- 27.5 vs. 53 +/- 11.3 hrs; p < .0001), greater creatinine concentrations on the first postoperative day (1.6 +/- 0.1 vs. 1.2 +/- 0.04 mg/dL; p = .0002), greater maximum creatinine concentration (2.4 +/- 0.2 vs. 1.3 +/- 0.1 mg/dL; p < .0001), and greater maximum bilirubin concentration (4.7 +/- 0.6 vs. 1.3 +/- 0.2 mg/dL; p < .0001) when compared with the control group. Five (32%) of 16 bacteremic patients died vs. none of the 95 control patients (p < .0001). CONCLUSIONS: Early bloodstream infection after cardiac surgery is uncommon and involves predominantly Gram-negative bacteria. The risk factors associated with bloodstream infection were preoperative morbidity and more complex surgery. Bloodstream infection was associated with a significantly adverse impact on outcome after cardiac surgery.

Analysis of Variance↗
PubMed1997

55- and 75-kilodalton tumor necrosis factor receptors mediate distinct actions in regard to human immunodeficiency virus type 1 replication in primary human macrophages.

We report in this study that repeated tumor necrosis factor alpha (TNF-alpha) pretreatment, starting before and continued after infection by human immunodeficiency virus type 1 (HIV-1), inhibits replication of the monocytotropic Ada strain in primary tissue culture-differentiated macrophages (TCDM), as assessed by sixfold lower levels of reverse transcriptase (RT) activity than that in untreated cells and absence of syncytium formation in TCDM cultures. In order to determine the pathways involved in inhibition of HIV-1 replication in primary TCDM pretreated with TNF-alpha, we tested TNF-alpha mutants T55 and T75, which recognize either the 55-kDa (TNF-R1) or the 75-kDa (TNF-R2) TNF receptor, respectively. Pretreatment of TCDM with the T75 mutant decreased the RT activity compared with that in untreated infected control cells fivefold and almost totally inhibited syncytium formation. In contrast, when TCDM were pretreated with the T55 mutant alone, syncytia were observed and RT activity was decreased about one-half. These results suggest that the inhibition of HIV-1 replication in TCDM pretreated with TNF-alpha might be mediated mainly through the 75-kDa TNF receptor (TNF-R2) rather than through the 55-kDa receptor (TNF-R1). Inhibition of HIV-1 replication in TCDM was observed with both T75 mutant pretreatment and posttreatment, starting at 1 h or 3 days after infection, whereas posttreatment with the T55 mutant, but not pretreatment, stimulated HIV-1 growth in primary TCDM. Both pre- and posttreatment with TNF-alpha inhibited HIV-1 replication in primary TCDM. The stimulation of HIV-1 replication by TNF-alpha in a chronically infected promonocytic cell line, U1, which contains two copies of integrated provirus, was mediated through the 55-kDa TNF-R1 alone and not through the 75-kDa TNF-R2. These results demonstrate that the 55-kDa TNF-R1 is involved in postintegration stimulation of HIV-1 while the 75-kDa TNF-R2 is involved in the inhibition of an early step of the viral life cycle in primary human TCDM.

Cell Line↗
PubMed1997

Measurement of exposure to mouse urinary proteins in an epidemiological study.

OBJECTIVES: To develop an assay to measure airborne mouse urinary protein (MUP) and to assess the occupational exposure to MUP in the workforce of three establishments as part of an epidemiological study examining the influence of aeroallergen exposure on the development of allergic respiratory disease. METHODS: Personal air samples were collected from nine exposure groups during a workshift. A sensitive and reproducible competitive inhibition assay, which used rabbit antisera specific for MUP, was developed and used to measure the occupational exposure to MUP. RESULTS: The personal measurements of MUP showed that people with direct contact with mice (animal technicians) had the highest exposure followed in decreasing order by those working with anaesthetised animals or their tissue (postmortem workers and scientists) and those with indirect contact with mice (supervisors, office workers, and slide production workers). The only difference in concentrations of MUP between the three establishments were found for cage cleaners, which reflected differences in working practises for this exposure category. Air samples collected during the performance of specific tasks showed that high exposures to MUP were associated with handling mice, indirect contact with mice, and washing floors. CONCLUSIONS: Exposure to mouse urinary proteins has been measured in the occupational environment. This information can be used to determine the relation between exposure to MUP and the development of allergic and respiratory disease.

Air Pollutants, Occupational↗
PubMed1997

Intralesional fluorouracil/epinephrine injectable gel for treatment of condylomata acuminata. A phase 3 clinical study.

BACKGROUND AND DESIGN: A new intralesional sustained-release chemotherapy is under development as a treatment for condylomata acuminata; it is administered as an injectable gel that consists of fluorouracil and epinephrine with a purified bovine collagen as the gellant (fluorouracil/epinephrine gel). In this randomized, double-blind study, we evaluated the safety and efficacy of this intralesional treatment in 401 patients, using 2 active drug formulations (fluorouracil/epinephrine gel and fluorouracil gel alone) and a placebo. Each lesion was injected once a week for up to 6 weeks, and patients were followed up for 3 months. RESULTS: A total of 359 patients with 1926 condylomata underwent evaluation. For all lesions treated with fluorouracil/epinephrine gel, the complete response (CR) rate was 77%. For all patients treated with fluorouracil/epinephrine gel, the CR rate was 61%. The fluorouracil/epinephrine gel was significantly more effective (P < .002) in treating condylomata than the fluorouracil gel without epinephrine (CR rate, 43%); both were superior to placebo (CR rate, 5%). At 3 months after completion of treatment, recurrence rates in patients with CRs were as follows: fluorouracil/epinephrine gel group, 50%; fluorouracil gel group, 58%. No clinically significant drug-related systemic reactions occurred. Finally, the type and severity of local tissue reactions of patients with a positive pretreatment collagen skin test result (6/401 [1.5%]) were similar to those of patients with a negative collagen skin test result. CONCLUSION: The fluorouracil/epinephrine injectable gel is a safe and effective treatment for condylomata acuminata.

Adolescent↗
PubMed1997

The impact of managed care on female caregivers in the hospital and home.

This article explores the connection between layoffs of nursing staff in hospitals, replacement of nurses with poorly trained aides, and the increasing burden on female family caregivers. It also discusses the centerpiece of managed care's cost containment efforts--reduced use of the hospital and earlier discharge of patients to the home. The article argues that these policies add to an increasing burden of care on female family caregivers and that US family policy does not support family caregiving. Finally, it recommends rigorous research to assess the social, emotional, and financial costs of nursing layoffs on nurses themselves as well as on female family caregivers.

Caregivers↗