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Biomedical subjects

S Becker

Publications and source records attributed to S Becker.

At least 55 records · Page 3Linked to original sources
PubMed2001

Impact of prophylaxis for Mycobacterium avium complex on bacterial infections in patients with advanced human immunodeficiency virus disease.

The epidemiology and natural history of bacterial infections among ambulatory patients with advanced human immunodeficiency virus (HIV) disease has not been well described. In this prospective study, 394 subjects were enrolled and followed at 8-week intervals for a median of 21 months. During follow-up, 164 (42%) of 394 patients developed at least 1 bacterial infection. The most common infections were sinusitis, bacterial pneumonia, skin and soft tissue infection, and bronchitis. Serious bacterial infections (defined as bacterial pneumonia, bacteremia, or deep visceral abscess) were reported by 56 subjects (14%). Female sex, age of <40 years, and Karnofsky score of < or =80 were independent risk factors for bacterial infections. Prophylaxis with clarithromycin, trimethoprim and sulfamethoxazole, or both had significant protective effect. The occurrence of any confirmed bacterial infection was associated with a significantly increased risk of mortality. This study documents that bacterial infections are common among patients with advanced HIV disease, especially among women.

AIDS-Related Opportunistic Infections↗
PubMed2001

Human alveolar macrophage responses to air pollution particulates are associated with insoluble components of coarse material, including particulate endotoxin.

Inhalation of particulate matter in the ambient air has been shown to cause pulmonary morbidity and exacerbate asthma. Alveolar macrophage (AM) are essential for effective removal of inhaled particles and microbes in the lower airways. While some particles minimally effect AM function others inhibit antimicrobial activity or cause cytokine and growth factor production leading to inflammation and tissue remodeling. This study has investigated the effects of water soluble (s) and insoluble (is) components of Chapel Hill, North Carolina ambient particulate matter in the size ranges 0.1-2.5 microm (PM2.5) and 2.5-10 microm (PM10) diameter, on human AM IL-6, TNFalpha, and MCP-1 cytokine production and host defense mechanisms including phagocytosis and oxidant production. Cytokines were found to be induced by isPM10 to a much higher extent (>50-fold) than sPM10, which in turn stimulated production better than isPM2.5, while sPM2.5 was inactive. Previous studies have indicated that endotoxin (ETOX) is a component of sPM10 responsible for cytokine production. Here, it is shown that inhibition of isPM10-induced cytokine production was partially achieved with polymyxin B and LPS-binding protein (LBP), but not with a metal chelator, implicating ETOX as a cytokine-inducing moiety also in isPM10. In addition to inducing cytokines, exposure to isPM10, but not the other PM fractions, also inhibited phagocytosis and oxidant generation in response to yeast. This inhibition was ETOX independent. The decrease in host defenses may be the result of apoptosis in the AM population, which was also found to be specifically caused by isPM10. These results show that the functional capacity of AM is selectively modulated by insoluble components of coarse PM, including the biocontaminant ETOX.

Adolescent↗
PubMed2001

A sensitive homologous radioimmunoassay for human relaxin-2 (h-RLX-2) based on antibodies characterized by epitope mapping studies.

We present a sensitive homologous radioimmunoassay (RIA) for the quantitative determination of human relaxin (hRLX) in human serum, plasma, seminal plasma, and urine. This assay is based on a rabbit antiserum which was generated using recombinant hRLX-2 as immunogen. Using 125I-hRLX-2 as tracer and a total incubation time of 20 - 24 hours the radioimmunoassay showed linearity in a range of 60 - 4000 ng/l, a lower detection limit of 38 ng/l and a mean recovery rate of 98.5%. Intraassay variation was 4.0% (mean = 526 ng/l) and 11.9% (mean = 2368 ng/l), and interassay variation 10.7% (mean = 256 ng/l) and 13.1% (mean = 2368 ng/l). Using hRLX-2 hexapeptides on polystyrene pins, epitopes recognized by the hRLX-2 specific rabbit antiserum were determined experimentally, and compared to predicted epitopes. Both methods led to comparable results. The antiserum, recognizing different epitopes, showed no cross-reactivity with human insulin, hZn-insulin, hIGF-I, hIGF-II, human inhibin alpha-subunit, two different forms of seminal plasma inhibin like peptide, spermolaxin, ubiquitin, prolactin, LH, FSH and hCG.

Amino Acid Sequence↗
PubMed2001

The black-pearl gene of Drosophila defines a novel conserved protein family and is required for larval growth and survival.

Using a transposon insertion line of the Drosophila Genome Project we have cloned the black-pearl gene (blp), analyzed cDNA clones, generated various mutants, and characterized their phenotypes. The blp gene codes for a protein of 15.7 kDa calculated molecular weight that has been conserved from yeast to plants and mammals with high homology. A domain of these new proteins shows distant similarity to DnaJ domains indicating a functionally relevant interaction with other proteins. The P element insertion in line P1539 lies within the 5' untranslated leader of the black-pearl gene. Flies homozygous for this insertion are semi-lethal, escapers produce very few offspring and show melanotic inclusions in the hemocoel ('black pearls') similar to various melanotic 'tumor' mutants. Two small deletions confined to the blp gene and two EMS-induced mutations are homozygous lethal. These null mutants appear normal up to a prolonged first instar larval stage but fail to grow and die. Thus in Drosophila the blp gene is specifically required for larval growth. The evolutionary conservation in both unicellular and multicellular organisms suggests for the new protein family described here a fundamental role in cell growth.

5' Untranslated Regions↗
PubMed2001

Adverse effects of MVA-T7 on the transport of Marburg virus glycoprotein.

Expression of glycoproteins has been carried out successfully using recombinant vaccinia virus vectors. Especially attractive is the use of recombinant vaccinia viruses which express the DNA-dependent RNA polymerase of the phage T7 (T7-polymerase). The T7-polynerase drives the transcription of plasmid-based genes under the control of the T7 RNA polymerase promoter transfected into the infected cell. Comparison of two different recombinant vaccinia viruses, vTF7-3 and MVA-T7, revealed that post-translational processing of Marburg virus surface glycoprotein (GP) is impaired in the MVA-T7 but not in the vTF7-3 system. Influenza virus hemagglutinin, however, was transported and processed like the authentic protein in both systems. It is shown that transport of GP in the MVA-T7 system is not completely blocked, but the vast majority of molecules remained Endo H-sensitive. Only trace amounts evaded the endoplasmatic reticulum and reached the plasma membrane. Thus, the adverse effects of MVA-T7 on the processing of recombinant glycoproteins cannot be predicted, and correct processing has to be investigated for every expressed glycoprotein.

Cell Membrane↗
PubMed2001

Hematogenous cervical spondylodiscitis after severe burn injury.

A 47-year-old man sustained a 31% TBSA burn injury. In spite of early escharectomy and mesh-graft-transplantation the patient suffered a septicaemic phase in the first week, which was treated by a specific antibiotic. Five weeks after the burn injury a cervical spondylodiscitis was diagnosed. Immediate wound debridement, ventral and dorsal spondylodesis with a tricortical bone-graft from the left iliac crest and titanium plates and specific antibiotic therapy led to the stabilization and healing of the cervical spinal column. The spondylodiscitis was microbiologically proved to be hematogenous after spread of Staphylococcus aureus from the blood in the early septicaemic phase. Swab culture from the burn surface wound, infected vertebrae and blood during the septicaemic phase revealed coagulase positive S. aureus. The aetiology, predisposing factors and management of this rare, but recognized, complication of major burns are discussed. Case features of this patient are compared with the single site's reported case of hematogenous cervical spondylodiscitis after severe burn injury.

Anti-Bacterial Agents↗
PubMed2001

Recovery profile and side effects of remifentanil-based anaesthesia with desflurane or propofol for laparoscopic cholecystectomy.

BACKGROUND: Nitrous oxide (N2O) has been suggested to contribute to bowel distension, resulting in worsened operating conditions for laparoscopic surgery, and to increase incidence of postoperative nausea and vomiting. Therefore, our objective was to assess the feasibility of two remifentanil-based anaesthetic regimens free from N2O with special regard to recovery profile, postoperative analgesic demand and side effects in patients undergoing laparoscopic cholecystectomy. METHODS: Fifty patients (ASA I-II, 23-65 yr) were randomly assigned to receive remifentanil-based anaesthesia in conjunction with propofol (group R/P) or desflurane (group R/D). After standardised induction of anaesthesia, analgesia was continued with remifentanil in all patients. For maintenance of hypnosis, propofol or desflurane were used in concentrations to ensure loss of consciousness, lack of awareness, and maintenance of heart rate and blood pressure within +/- 25% of initial values. At the end of surgery all anaesthetics were discontinued without tapering and early emergence and recovery were recorded. Pain scores were assessed by using a visual analogue scale. Patient-controlled analgesia with i.v. piritramide was used for treatment of postoperative pain and recorded for 90 min in the postanaesthesia care unit (PACU). In addition, side effects were noted. RESULTS: Early emergence from anaesthesia did not differ between the groups. In group R/P, time to eye opening, spontaneous respiration and extubation was 4.4 +/- 2.9 min, 5.2 +/- 3.4 min and 5.5 +/- 3.3 min respectively, compared with 4.7 +/- 2.7 min, 5.3 +/- 2.4 min and 5.7 +/- 2.5 min in group R/D. While pain scores did not differ between both groups on admission to the PACU, patients receiving desflurane required more i.v. piritramide as compared to those receiving propofol, 22.0 +/- 6.5 mg and 17.9 +/- 7.0 mg, respectively (P<0.05). Nausea was less frequent after propofol (16% vs. 48%, P<0.05). CONCLUSION: In patients undergoing laparoscopic cholecystectomy, remifentanil-based anaesthetic regimens in conjunction with propofol or desflurane are suitable and allow for rapid recovery from anaesthesia. However, the use of propofol results in less postoperative analgesic consumption and nausea as compared to desflurane.

Adult↗
PubMed2001

Cellular immunotherapy of malignancies using the clonal natural killer cell line NK-92.

For years activated natural killer (A-NK) cells have been explored with respect to their efficacy in anticancer therapy, but, except for some anectdotal reports, no clear clinical benefit has been shown. However, as the understanding about the interactions of NK cells and tumor cells advances, the use of A-NK cells might be revisited with more sophisticated approaches that pay tribute to mechanisms which allow tumor cells to escape immune surveillance. Here the highly cytotoxic NK cell line NK-92 seems to be an attractive alternative for use in adoptive immunotherapy, because it was shown to exhibit substantial antitumor activity against a wide range of malignancies in vitro as well as in xenografted SCID mice. NK-92 cells are characterized by an almost complete lack of killer cell immunglobulin-like receptors (KIRs) yet conserved ability to perforin and granzyme B-mediated cytolytic activity, which make them unique among the few established NK and T cell-like cell lines. NK-92 is the only natural killer cell line that has entered clinical trials. Here we discuss the current status of development of this cell line for adoptive immunotherapy (AIT) of malignancies and review our first clinical experience in patients with advanced cancer who have received repeated transfusions of irradiated NK-92 in a phase I/II trial. Also we discuss issues that address safety aspects of immunotherapy with clonal cell lines and describe further manipulations, which hold the potential of significantly improving the clinical outcome of AIT with NK-92.

Cell Culture Techniques↗
PubMed2001

Husbands' and wives' reports of contraceptive use.

Many Demographic and Health Surveys (DHS) in the past decade have queried husbands and wives about their current contraceptive use. In this study, couples' concurrence on use and method used is compared by means of data from 23 countries, mostly in sub-Saharan Africa. Husbands report higher levels of use than do their wives in every country studied, with ranges from 2 percent higher (Brazil) to 150 percent higher (Mali). Many of the discrepancies are the result of husbands' sole reports of periodic abstinence and condom use. Couples with polygynous husbands show less concurrence than do monogamous couples, although the majority of these differences could result from a data-collection problem. Monogamous couples in which one or both spouses reported having extramarital sex partners show less concurrence than do monogamous couples reporting no other partners. Problems of validity of both husbands' and wives' reports are discerned, and in the few instances where a direct comparison is possible, wives' reports are shown to have greater validity. Logistic regression results show that spousal discussion about family planning and greater female education are consistent predictors of concurrence.

Adolescent↗
PubMed2001

Sorting of Marburg virus surface protein and virus release take place at opposite surfaces of infected polarized epithelial cells.

Marburg virus, a filovirus, causes severe hemorrhagic fever with hitherto poorly understood molecular pathogenesis. We have investigated here the vectorial transport of the surface protein GP of Marburg virus in polarized epithelial cells. To this end, we established an MDCKII cell line that was able to express GP permanently (MDCK-GP). The functional integrity of GP expressed in these cells was analyzed using vesicular stomatitis virus pseudotypes. Further experiments revealed that GP is transported in MDCK-GP cells mainly to the apical membrane and is released exclusively into the culture medium facing the apical membrane. When MDCKII cells were infected with Marburg virus, the majority of GP was also transported to the apical membrane, suggesting that the protein contains an autonomous apical transport signal. Release of infectious progeny virions, however, took place exclusively at the basolateral membrane of the cells. Thus, vectorial budding of Marburg virus is presumably determined by factors other than the surface protein.

Animals↗
PubMed2001

Association between airway hyperreactivity and bronchial macrophage dysfunction in individuals with mild asthma.

Little is known about the functional capabilities of bronchial macrophages (BMs) and their relationship to airway disease such as asthma. We hypothesize that BMs from asthmatics may be modulated in their function compared with similar cells from healthy individuals. BMs obtained by induced sputum from mild asthmatics (n = 20) and healthy individuals (n = 20) were analyzed using flow cytometry for CD16, CD64, CD11b, CD14, and human leukocyte antigen-DR expression, phagocytosis of IgG opsonized yeast, and oxidant production. Asthma status was assessed by lung function [percent predicted forced vital capacity and forced expiratory volume in 1 s (FEV(1))], percent sputum eosinophils, and nonspecific airway responsiveness [provocative concentration that produces a 20% fall in FEV(1) (PC(20,FEV1))]. Asthmatics with >5% airway eosinophils (AEo+) had decreased BM CD64 expression and phagocytosis compared with asthmatics with <5% eosinophils (AEo-). Among asthmatics, a significant correlation was found between CD64 expression and BM phagocytosis (R = 0.7, P < 0.009). Phagocytosis was also correlated with PC(20,FEV1) (R = 0.6, P < 0.007), lung function (%predicted FEV(1), R = 0.7, P < 0.002) and percent eosinophils (R = -0.6, P < 0.01). In conclusion, BM from asthmatics are functionally modulated, possibly by Th2 cytokines involved in asthma pathology.

Adult↗
PubMed2001

Inhalation of PM2.5 does not modulate host defense or immune parameters in blood or lung of normal human subjects.

We tested the hypothesis that exposure of healthy volunteers to concentrated ambient air particles (CAPS) between 0.1 and 2.5 microm in diameter is associated with modulation of human alveolar macrophage (AM) function, cytokine production, and immune phenotype in both blood and lung. Thirty-eight volunteers were exposed to either filtered air or CAPS from the immediate environment of the U.S. Environmental Protection Agency human studies facility in Chapel Hill, North Carolina, USA. Particle concentrations in the chamber during the exposures ranged from 23.1 to 311.1 microg/m3. No symptoms were noted by volunteers after the exposure. Eighteen hours after exposure, analysis of cells obtained by bronchoalveolar lavage (BAL) showed a mild increase in neutrophils in both the bronchial (8.4 +/- 2%) and alveolar fractions (4.2 +/- 1.7%) in subjects exposed to the highest concentration of CAPS compared to neutrophils in the fluids of those exposed to filtered air (bronchial fraction 2.7 +/- 0.6%; alveolar fraction 0.8 +/- 0.3%). There was no change in the percentage of lymphocytes or AMs recovered in the lavage after inhalation of the highest particle levels (mean 207 microg/m3). There was also no change in the proportion of lymphocytes in the BAL expressing CD3, CD4, CD8, CD19, nor activation markers CD25 or CD69. Particle inhalation did not affect the expression of CD11b, CD64, CD16, CD14, CD71 on AM, nor was there an effect on phagocytosis or oxidant generation following stimulation with zymosan A. IL-6 and IL-8 levels detected by enzyme-linked immunoabsorbent assay in the BAL were unrelated to inhaled particle levels. The distribution of lymphocyte subsets in blood obtained 18 hr after exposure to CAPS did not differ from that found before exposure. We conclude that ambient air particles are capable of inducing a mild inflammation in the lower respiratory tract but have no effect on immune phenotype or macrophage function under the conditions tested.

Administration, Inhalation↗
PubMed2001

Exclusive breastfeeding reduces acute respiratory infection and diarrhea deaths among infants in Dhaka slums.

OBJECTIVES: To describe breastfeeding practices and investigate the influence of exclusive breastfeeding in early infancy on the risk of infant deaths, especially those attributable to respiratory infections (ARI) and diarrhea. METHODS: A prospective observational study was conducted on a birth cohort of 1677 infants who were born in slum areas of Dhaka in Bangladesh and followed from birth to 12 months of age. After enrollment at birth, the infants were visited 5 more times by 12 months of age. Verbal autopsy, based on a structured questionnaire, was used to assign a cause to the 180 reported deaths. Proportional hazards regression models were used to estimate the effect of breastfeeding practices, introduced as a time-varying variable, after accounting for other variables, including birth weight. Overall neonatal, postneonatal and infant mortality, and mortality attributable to ARI and diarrhea were measured. RESULTS: The proportion of infants who were breastfed exclusively was only 6% at enrollment, increasing to 53% at 1 month and then gradually declining to 5% at 6 months of age. Predominant breastfeeding declined from 66% at enrollment to 4% at 12 months of age. Very few infants were not breastfed, whereas the proportion of partially breastfed infants increased with age. Breastfeeding practices did not differ between low and normal birth weight infants at any age. The overall infant mortality rate was 114 deaths per 1000 live births. Compared with exclusive breastfeeding in the first few months of life, partial or no breastfeeding was associated with a 2.23-fold higher risk of infant deaths resulting from all causes and 2.40- and 3.94-fold higher risk of deaths attributable to ARI and diarrhea, respectively. CONCLUSION: The important role of appropriate breastfeeding practices in the survival of infants is clear from this analysis. The reduction of ARI deaths underscores the broad-based beneficial effect of exclusive breastfeeding in prevention of infectious diseases beyond its role in reducing exposure to contaminated food, which may have contributed to the strong protection against diarrhea deaths.

Bangladesh↗
PubMed2001

Imaging ventures: a legal primer.

As the technology for imaging continues to improve, we expect the number of non-radiologists having some involvement in imaging ventures to increase significantly. Further, the variations and numbers of types of ventures will also likely increase.

Antitrust Laws↗
PubMed2001

[Contrast-enhanced MRA of the carotid arteries using 0.5 Tesla: comparison with selective digital angiography].

PURPOSE: To assess the feasability, the imaging quality and the effectiveness of contrast-enhanced MRA (CE MRA) using a 0.5 Tesla MR unit in the evaluation of internal carotid artery (ICA) stenosis. Materials and Methods. 29 patients underwent CE MRA and selective digital substraction angiography (DSA). All data were reviewed in a blinded fashion by 2 independant observers. Imaging quality was graded as good, moderate but interpretable, and insufficient. Stenosis was graded according to the NASCET classification from grade 1 to 4, with the following thresholds:<30%,<70%,<99% and occlusion. Inter and intra- observer agreement was evaluated using the kappa index. RESULTS: Imaging quality was good for 79 arteries, moderate for 24 and insufficient for 13 (k MRA=0.72 and 0.64 respectively for the right and left ICAs). Interobserver agreement was good with values for right/left ICA of 0.84/0.94, 0.72/0.74 respectively for CE-MRA and DSA. For the comparison between CE MRA and DSA, agreement was also good, with values of 0.74 and 0.64 for both readers. Sensitivity of CE MRA in the detection of hemodynamically significant stenosis (>70%) was of 0.95 and 0.94 and specifity of 0.91 and 0.89 respectively for reader n degrees 1 and reader n degrees 2. CONCLUSION: CE MRA using a 0.5T MR unit is a valuable technique in the evaluation of ICA stenosis.

Adult↗