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Biomedical subjects

S Herbert

Publications and source records attributed to S Herbert.

18 recordsLinked to original sources

Localization of Staphylococcus aureus in infected airways of patients with cystic fibrosis and in a cell culture model of S. aureus adherence.

Staphylococcus aureus causes chronic respiratory tract infections in patients with cystic fibrosis (CF). Using immunofluorescence and scanning and transmission electron microscopy we located S. aureus in lung specimens of three infected CF patients, in a nasal polyp of one CF patient, and in a suspension cell culture system of primary nasal epithelial cells in vitro. Very little of S. aureus was attached to the lung epithelium, whereas abundant S. aureus was detectable in the mucus of obstructed airways. Similarly, S. aureus adhered to components of secreted mucus on primary nasal epithelial cells of CF patients and healthy control subjects, grown as cell balls in vitro (bacteria/cell +/- SD: CF: 21.9 +/- 1.5; controls: 22. 0 +/- 5.8). Mucus depletion of cell balls prior to incubation with S. aureus resulted in a significantly reduced binding (bacteria/cell +/- SD: CF: 4.2 +/- 0.3; P < 0.001; controls: 5.0 +/- 1.3; P < 0. 007). Binding of S. aureus to cell balls from CF patients or control subjects did not differ significantly. When cell balls were treated with human neutrophil elastase, hypersecretion caused removal of S. aureus from cell-associated mucus. The results suggest that S. aureus adheres primarily to mucus components of the respiratory epithelium and that significant differences do not exist in binding of S. aureus to CF or non-CF cells.

Adolescent

Policy instruments for reducing toxic releases. The effectiveness of state information and enforcement actions.

This article analyzes the extent to which different policy instruments explain toxic reductions among the states. Data from the Toxics Release Inventory (TRI) and other sources are used to assess the effect of various policy instruments, while holding economic factors constant. State TRI information programs, enforcement action, and direct regulation all matter in reducing toxic releases. Interestingly, the informational tool seems to matter more than both authoritative tools. The findings also support the idea that the interaction of policy instruments as well as the match between policy tools and policy context may account for a portion of the results.

Hazardous Substances

Adverse perinatal outcome in parturients who use crack cocaine.

OBJECTIVE: To determine the risk of adverse pregnancy outcome among crack cocaine users in a large homogeneous prenatal population with objective documentation of drug use. METHODS: A retrospective cohort study was performed on a population of inner-city women who were offered routine voluntary urine drug screening and who delivered between January and December 1992 at a large county hospital. The study population consisted of 483 users (positive drug screens) and 3158 non-users (negative drug screens). Univariate analysis and multiple logistic regression were used to identify the relation between crack cocaine use and adverse perinatal outcome. RESULTS: Users were significantly more likely than nonusers to deliver low birth weight (LBW) infants (31.3% versus 14.9%; crude odds ratio [OR] 2.6; 95% confidence interval [CI] 2.1, 3.2), growth-restricted infants (29.0% versus 13.0%; crude OR 2.7; 95% CI 2.2, 3.4), and preterm infants (28.2% versus 17.1%; crude OR 1.9; 95% CI 1.5, 2.4). In addition, users were more likely to have abruptions (3.3% versus 1.1%; crude OR 3.0; 95% CI 1.6, 5.6) and infants with low 5-minute Apgar scores (7.9% versus 4.5%; crude OR 1.8; 95% CI 1.2, 2.7). After adjusting for confounders (including alcohol use and smoking), only the risks of LBW and fetal growth restriction (FGR) remained significant, with adjusted OR 1.6 (95% CI 1.03, 2.4) and adjusted OR 1.7 (95% CI 1.2, 2.3), respectively. Although there was no significant difference in the rate of low 5-minute Apgar scores between users and non-users after controlling for confounders, users with a positive urine drug screen within 1 week of delivery were significantly more likely than non-users to deliver infants with low 5-minute Apgar scores: crude OR 2.4; adjusted OR 2.0 (95% CI 1.1, 3.7). CONCLUSION: In this inner-city population, crack cocaine use is associated with adverse pregnancy outcomes, as noted by increased risks of LBW and FGR.

Adolescent

Regulation of Staphylococcus aureus capsular polysaccharide type 5: CO2 inhibition in vitro and in vivo.

Staphylococcus aureus capsular polysaccharide type 5 (CP5) expression was investigated in lung tissue and nasal polyps of two cystic fibrosis (CF) patients, in rats, and in vitro using ELISA and IFA. In CF tissues, S. aureus expressed protein A and teichoic acid but only 1%-5% of cells expressed CP5. When rats were challenged with CP5-positive S. aureus in the granuloma pouch model, only 1%-5% of CP5-positive cells were detectable in pouch exudates. CF and pouch isolates, however, reexpressed CP5 (70%-90% of cells) when grown in vitro with air. Addition of > or = 1% CO2 to air or to O2/N2 gas mixtures reduced CP5 expression significantly (P < .001) in a dose-dependent manner (6%-1% CP5-positive cells). The results show that S. aureus does not produce CP5 in CF airways and in rat granuloma pouches and that CO2 is an environmental signal that regulates CP5 expression.

Animals

[Regulation of Staphylococcus aureus capsular polysaccharide type 5: in vitro and in vivo inhibition by CO2].

Staphylococcus aureus capsular polysaccharide type 5 (CP5) expression was investigated in lung tissue and nasal polyps of two cystic fibrosis (CF) patients, in rats and in vitro using ELISA and immunofluorescence. In CF tissues, S. aureus expressed protein A and teichoic acid but only 1-5% of cells expressed CP5. When rats were challenged with CP5-positive S. aureus in the granuloma pouch model, only 1-5% CP5-positive cells were detectable in pouch exsudates. CF and pouch isolates, however, re-expressed CP5 (70-90% of cells) when grown in vitro with air. Addition of 1% CO2 or more to air or to O2/N2 gas mixtures reduced CP5 expression significantly (p < 0.001) in a dose-dependent manner (1-6% CP5-positive cells). The results show that S. aureus does not produce CP5 in CF airways and in rat granuloma pouches and that CO2 is an environmental signal which regulates CP5 expression.

Adult

Cleavage of lymphocyte surface antigens CD2, CD4, and CD8 by polymorphonuclear leukocyte elastase and cathepsin G in patients with cystic fibrosis.

Polymorphonuclear leukocytes (PMN) accumulating in airways of patients with cystic fibrosis (CF) as a response to chronic endobronchial bacterial lung infection, release lysosomal serine proteinases such as PMN-elastase at concentrations of approximately 0.5 microM to 5 microM into the airway lumen. Immunohistology of CF lung material and fluorescence activated cell sorter analysis of sequential CF bronchoalveolar lavages demonstrated loss of the CD4 and CD8 Ag on CD3+ T lymphocytes in sputum-filled airways. In 10 CF sputum samples 1.0%, 19.1%, and 15.7% of all CD3+ T lymphocytes expressed CD4, CD8, and CD2, respectively. Incubation of CF sputum supernatant fluids with peripheral blood T lymphocytes resulted in total reduction of CD4 and CD8 but not CD2. Addition of alpha 1-proteinase inhibitor abolished surface Ag cleavage completely. Purified PMN-elastase and cathepsin G cleaved CD2, CD4, and CD8 on peripheral blood T lymphocytes at proteinase concentrations of 0.83 to 8.3 microM in a dose-dependent manner. Cleaved CD4 and CD8 were reexpressed on the surface of T lymphocytes after 24 h in the absence of PMN-elastase. Incubation of a CD4+ T cell clone with PMN-elastase lead to a significant reduction of cytotoxicity toward target cells and significantly reduced IL-2 and IL-4 production. The results suggest a temporary functional impairment of T lymphocytes in foci of high inflammation characterized by stimulated PMN, which may lower tissue destruction.

Adult

HLA-A*8001 is a member of a newly discovered ancient family of HLA-A alleles.

A member of a new HLA-A locus family, HLA-A*8001, has been characterized from 3 African-American individuals expressing a unique HLA-A serologic specificity. The HLA-A*8001 sequence is most closely related to alleles of the HLA-A1/3/11 family, although it also contains residues characteristic of the HLA-A2/28, -A9, -A10, and -A19 families. More importantly, the HLA-A*8001 sequence contains four unique nonsynonymous (amino acid replacing) nucleotide substitutions absent from all other primate A locus alleles. In addition, five other nucleotide substitutions, four nonsynonymous and one synonymous (silent), observed only in non-human primate A locus alleles were found. Neighbor-joining tree analysis of HLA-A*8001 supports the notion that the HLA-A*8001 allele is a member of a new HLA-A locus family which was derived from the ancestral A3 lineage but diverged early in the evolution of the HLA-A locus.

Alleles

Vitamin D3 production by cultured human keratinocytes and fibroblasts.

We have demonstrated that monolayers of human cultured newborn foreskin keratinocytes and fibroblasts elaborate vitamin D3 following exposure to UV-B. This in vitro system provides a new means to study those factors (hormones, ions, vitamin D3 metabolites, etc.) that regulate the production of vitamin D3 by human skin cells. Vitamin D3 production was enhanced greatly by using cells that were pre-treated with AY-9944, a non-toxic drug that inhibits cholesterologenesis while elevating cellular levels of 7-dehydrocholesterol, the sterol precursor of vitamin D3. The pre-D3 formed within viable, irradiated cells is transformed to D3 within a matter of hours at 37 degrees C, and keratinocytes proved to be more proficient sources of the vitamin and its metabolites than corresponding skin fibroblasts.

Acetates

Simplifying radiological examinations. The urogram as a model.

The diagnostic yield of one and three film urograms was compared with that of complete examinations to determine whether a moderately complex examination could be simplified without loss of important diagnostic information. Although sensitivity was high (88-93%) and was not altered by increasing the complexity of the examination, the definitive disease diagnoses were more accurate with the three film rather than the one film studies. Specificity increased from 69% to 77-80% with the more complex examinations. A strategy based on terminating the examination if the single film urogram is normal with a three-film examination in positive cases might effect considerable savings, both economic and in terms of gonadal radiation dose, without serious diagnostic loss.

Cost-Benefit Analysis

When should pre-term babies be sent home from neonatal units?

20 randomly selected infants of 33 weeks gestation and under at birth were allowed to go home from the neonatal unit provided they were clinically well and had passed the nadir of their postnatal weight-loss and provided home conditions were satisfactory. Weight-gain at home was satisfactory and there was no increased rate of hospital readmission compared with 20 randomly selected pre-term infants who were discharged at a more traditional weight of 2200 g. There is therefore little justification for the widespread practice in Britain of delaying discharge of preterm infants until they reach a predetermined weight (usually 2000--2500 g).

Body Weight

A team approach to the treatment of dysphagia.

This paper looks at dysphagia and the difficulties it causes for patients and those caring for them. It describes an initiative developed to ensure a consistent multidisciplinary approach to management of patients with dysphagia.

Deglutition Disorders