Asthma hospitalization trends in Charleston, South Carolina, 1956 to 1997: twenty-fold increase among black children during a 30-year period.

OBJECTIVE: The increase in asthma prevalence has been documented worldwide, affecting many races living in many different climates. Multiple studies have demonstrated that the most striking prevalence and morbidity of asthma in the United States has been in black children, but little research has determined the scale of the increase, or specifically when the disease became severe in this group. This study sought to determine exactly when the rise in asthma hospitalizations among black patients began and what the pattern of asthma hospitalizations has been in different races and age groups over a 40-year period in 1 urban area. METHODS: A retrospective chart review of discharges from the Medical University of South Carolina was conducted from 1956 to 1997. Charts with the primary discharge diagnosis of asthma were examined for discharge date, race, and age group (0- to 4-year-olds, 5- to 18-year-olds, 19- to 50-year-olds, > or =51-year-olds). The diagnostic codes used were based on the International Classification of Diseases (ICD)-6, 1956-1957; ICD-7, 1958-1967; ICD-8, 1968-1978; and ICD-9, 1979-1997. Over the period studied, this hospital was the primary inpatient provider for children in this area, and the only provider for uninsured children. Between 1960 and 1990, the racial makeup of the area remained stable, as did the percentage of blacks living at the poverty level. The raw number of asthma discharges, rate per 10 000 discharges of the same race, and rate per 100 000 population in Charleston County were tabulated for each age group and racial category. RESULTS: Over the time period examined, there has been a progressive increase in asthma hospitalizations in black individuals of all age groups and in whites under 18 years. The most striking increase has been in black children 0 to 18 years old (figure). The increase either as raw values or as a rate per 100 000 began around 1970, and was linear. This increase in black children discharged with asthma as a rate per 100 000 population was 20-fold: the rate increased from 18 in 1970 to 370 in 1997. Asthma discharges as a rate per 10 000 black children discharged increased by 24-fold from 1960 to 1997. Total discharges from the hospital increased from 49 000 to 128 000 per year over this period. Blacks made up only 28% of discharges in 1957, but that proportion increased to 56% in 1960 and remained relatively stable over the following 35 years. The increase seen in white children 0 to 18 years of age as a rate per 100 000 population was 5-fold and began around 1980. Both increases seem to be consistent over the time period studied, and continued to 1997. [figure: see text]. CONCLUSIONS: Among a predominantly poor black population living in a southern US city, there has been a steady increase in childhood asthma hospitalizations over the past 30 years. A significant although less dramatic rise has occurred in white children. Over this time period, although there have been many changes in lifestyle that could have contributed to this rise, there have been no major changes in housing conditions for poor patients. In addition, Medicaid coverage for children in South Carolina did not change significantly until 1999. The time course of these increases parallels increases reported in other Western populations, suggesting that there must be 1 or more common factors contributing to the rise. Many explanations have been offered for the changes in incidence and severity of asthma. The scale of the change, time course, and linearity of the increase in this study represent a challenge to many of the hypotheses proposed to explain this epidemic.

Identification of a DNA binding region in GerE from Bacillus subtilis.

Proteins that have a structure similar to those of LuxR and FixJ comprise a large subfamily of transcriptional activator proteins. Most members of the LuxR-FixJ family contain a similar amino-terminal receiver domain linked by a small region to a carboxy-terminal domain that contains an amino acid sequence similar to the helix-turn-helix (HTH) motif found in other DNA-binding proteins. GerE from Bacillus subtilis is the smallest member of the LuxR-FixJ family. Its 74-amino-acid sequence is similar over its entire length to the DNA binding region of this protein family, including the HTH motif. Therefore, GerE provides a simple model for studies of the role of this HTH domain in DNA binding. Toward this aim, we sought to identify the amino acids within this motif that are important for the specificity of binding to DNA. We examined the effects of single base pair substitutions in the high-affinity GerE binding site on the sigK promoter and found that nucleotides at positions +2, +3, and +4 relative to the transcription start site on the sigK promoter are important for a high-affinity interaction with GerE. We next examined the effects of single alanine substitutions at two positions in the HTH region of GerE on binding to wild-type or mutant target sites. We found that the substitution of an alanine for the threonine at position 42 of GerE produced a protein that binds with equal affinity to two sites that differ by 1 bp, whereas wild-type GerE binds with different affinities to these two sites. These results provide evidence that the amino acyl residues in or near the putative HTH region of GerE and potentially other members of the LuxR-FixJ family determine the specificity of DNA binding.

Molecular characterization of hasC from an operon required for hyaluronic acid synthesis in group A streptococci. Demonstration of UDP-glucose pyrophosphorylase activity.

Hyaluronic acid is a high molecular weight glycosaminoglycan composed of repeating subunits of glucuronic acid and N-acetylglucosamine. It is synthesized by the group A streptococcal membrane-associated enzyme hyaluronate synthase. In previous reports, the locus required for expression of hyaluronic acid, the has operon, was identified and found to consist of two genes, hasA and hasB encoding hyaluronate synthase and UDP-glucose dehydrogenase, respectively. Since a transcription terminator was not found at the end of hasB, it was the aim of this study to identify the remaining gene(s) in the has operon. By utilizing the Tn1000 method of DNA sequencing and inverse polymerase chain reaction, hasC, the third gene in the has operon was shown to be 915 base pairs in length (304 amino acids) and located 192 base pairs downstream of hasB. Sequence similarities to other genes suggested that hasC encodes UDP-glucose pyrophosphorylase. Overexpression of hasC using isopropyl-1-thio-beta-D-galactopyranoside induction of the T7 promoter in the pET translation system allowed for the production of bacterial extracts from Escherichia coli that possessed increased UDP-glucose pyrophosphorylase activity as compared to nondetectable levels in extracts with vector alone. In addition, expression of HasC resulted in a protein of approximately 36 kDa as shown by SDS-polyacrylamide gel electrophoresis. These data as well as complementation analysis of hasC in an E. coli galU mutant confirmed that hasC encodes UDP-glucose pyrophosphorylase. Finally, since sequence analysis identified a potential rho-independent transcription terminator at the 3-prime terminus of the gene, hasC is the third and probably the final gene in the has operon.

Hyaluronic acid synthesis operon (has) expression in group A streptococci.

The has operon is composed of three genes, hasA, hasB, and hasC that encode hyaluronate synthase, UDP-glucose dehydrogenase, and presumptively UDP-glucose pyrophosphorylase, respectively. Expression of the has operon was shown to be required for the synthesis of the hyaluronic acid capsule in group A streptococci. Previous studies indicated that some group A and group C streptococcal strains produce the hyaluronic acid capsule, while others do not. In addition, it was observed that encapsulated strains cultured in stationary phase of growth lose the hyaluronic acid capsule. Therefore, the molecular mechanisms controlling the expression of the hyaluronic acid capsule in group A streptococci was investigated. In this study, it was determined that all encapsulated and unencapsulated strains of group A streptococci as well as encapsulated group C streptococci analyzed possess the has operon locus. The acapsular phenotype was accounted for by the absence of hyaluronate synthase activity in the membrane and not the production of extracellular hyaluronidase. A has operon mRNA transcript was not expressed by unencapsulated strains of group A streptococci, whereas encapsulated strains of group A streptococci grown to mid to late exponential phase produced the hyaluronate capsule, as well as has operon mRNA. However, as the streptococci entered the stationary phase of growth, they became acapsular and this was concomitant with the loss of has operon mRNA transcript. These results were confirmed by primer extension analyses of RNA isolated from encapsulated and unencapsulated strains of group A streptococci as well as RNA prepared from encapsulated strains cultured in exponential and stationary phases of growth. Thus, the loss of has operon mRNA in unencapsulated group A streptococci, as well as growth phase regulation occurs at the previously mapped has operon promoter. These data suggested that the synthesis of the hyaluronic acid capsule for group A streptococci may be controlled by transcriptional mechanisms.

Zingiber officinale (ginger) used to prevent 8-Mop associated nausea.

Patients undergoing photopheresis are required to ingest the drug 8-MOP as part of their treatment. This drug causes nausea as a side effect. Ginger taken prior to 8-MOP may substantially reduce this side effect. This study compared patients' nausea when taking 8-MOP with and without ginger.

Purification, characterization, and cDNA cloning of an AU-rich element RNA-binding protein, AUF1.

The degradation of some proto-oncogene and lymphokine mRNAs is controlled in part by an AU-rich element (ARE) in the 3' untranslated region. It was shown previously (G. Brewer, Mol. Cell. Biol. 11:2460-2466, 1991) that two polypeptides (37 and 40 kDa) copurified with fractions of a 130,000 x g postribosomal supernatant (S130) from K562 cells that selectively accelerated degradation of c-myc mRNA in a cell-free decay system. These polypeptides bound specifically to the c-myc and granulocyte-macrophage colony-stimulating factor 3' UTRs, suggesting they are in part responsible for selective mRNA degradation. In the present work, we have purified the RNA-binding component of this mRNA degradation activity, which we refer to as AUF1. Using antisera specific for these polypeptides, we demonstrate that the 37- and 40-kDa polypeptides are immunologically cross-reactive and that both polypeptides are phosphorylated and can be found in a complex(s) with other polypeptides. Immunologically related polypeptides are found in both the nucleus and the cytoplasm. The antibodies were also used to clone a cDNA for the 37-kDa polypeptide. This cDNA contains an open reading frame predicted to produce a protein with several features, including two RNA recognition motifs and domains that potentially mediate protein-protein interactions. These results provide further support for a role of this protein in mediating ARE-directed mRNA degradation.

Photopheresis for ARC: a nursing perspective.

Photopheresis, an approved treatment for cutaneous T-cell lymphoma (CTCL), is the basis of a trial involving patients with AIDS-related complex (ARC). This study has provided the opportunity to identify unique nursing challenges along with satisfaction from innovative nursing interventions.

Photopheresis for the treatment of cutaneous T cell lymphoma.

We investigated the use of extracorporeal chemotherapy (photopheresis) in eight patients with cutaneous T cell lymphoma. Initially described by Edelson et al. for the treatment of erythrodermic cutaneous T cell lymphoma, we have expanded the treatment to include patients with extensive patch/plaque disease as well as tumor-stage disease. Four of five patients with erythrodermic stage disease had either a complete or a partial clinical remission with photopheresis alone. One patient with extensive patch/plaque disease continued to have a partial clinical remission of 7 months' duration with photopheresis alone. Of the two patients with tumor-stage disease, one remained without evidence of clinical disease at 10 months with photopheresis alone, whereas the second patient had a partial clinical remission of 5 months with a combination of local radiation therapy followed by monthly photopheresis. The skin biopsy specimen obtained from the patient with tumor-stage disease in complete clinical remission did not show cutaneous T cell lymphoma. We conclude that photopheresis is an effective modality alone or in combination with adjunctive therapy for erythroderma, extensive patch/plaque disease, and some tumor-stage disease.

Hemoglobin function in stored blood. XIII. A citrate-adenine preservative with optimal pH to maintain red cell 2,3-DPG (function) and ATP (viability).

Increasing pH by a 0.5 increment over the commonly used preservative, acid-citrate-dextrose with adenine (ACD-Ad), results in a significant improvement in 2,3-DPG, with no significant loss in concentrations of ATP. The intermediate pH preservative, 6.0, also had ATP concentrations which equaled those of the low pH preservatives, 5.0 and 5.5, from the 21st to the 42nd day of storage. A citrate-adenine preservative, with a pH between 5.5 and 6.0, would seem to be optimal for maintenance of hemoglobin function and red cell viability, as determined by measurements of 2,3-DPG and ATP concentrations.