Evaluation of synthetic,M type-specific peptides as antigens in a multivalent group A streptococcal vaccine

The recent development of emm gene sequence-based typing methodology has allowed group A streptococci (GAS) M serotype prevalence data to be determined. This information has been used to identify the components of a multivalent M protein peptide vaccine that could theoretically prevent most of the GAS-mediated diseases in the USA. In this study, we have evaluated in mice the immunogenicity and protective ability of multiple synthetic, M type-specific peptides, derived from the N-termini of three prevalent GAS serotypes (three peptides per serotype, total of nine peptides). At least one peptide, representing each of the three M types tested, was immunogenic. Five of the nine synthetic peptides tested, elicited an immune response in mice, and sera raised against four of the peptides, all possessed functional activity as demonstrated in a bactericidal assay. In vivo nasopharyngeal challenge experiments were carried out with peptides from the M1 (peptide M1-3) and M3 (peptide M3-2) proteins induced in vivo immune protection by reducing intranasal carriage.Reduction in colonization for M1-3 and M3-2 was 90% (P=0.02) and 66% (P<0.17), respectively. A reduction in colonization of 67% (P=0.03) was observed for M3-2 immunized mice when M43, a heterologous serotype, was used as the challenge strain. These results show the utility of synthetic, M type-specific peptides as antigens in a multivalent GAS vaccine.     

Case-control study of intracranial tumors among employees at a petrochemical research facility

This case-control study evaluated the relation between potential exposure to chemical and physical agents and the occurrence of intracranial tumors among employees at a petrochemical research facility. Cases were employees with glioma (n = 6) or benign intracranial tumors (n = 6). Controls (n = 119) were individually matched to cases on gender and birth year, and they were alive and did not have an intracranial tumor at the case's diagnosis date. Exposure information came from interviews with subjects or surrogates and from corporate records on agents used in research projects. Analyses computed matched odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for self-reported exposure to 15 agents and project-based estimates of exposure to 29 agents. For gliomas, the OR was elevated for self-reported exposure to ionizing radiation (OR, 15.7; CI, 1.4 to 179.4), n-hexane (OR, infinity; CI, 1.4 to infinity), organometallics (OR, 9.4; CI, 1.5 to 59.7), and amines other than nitrosamines (OR, 6.0; CI, 1.0 to 35.7). The OR also was elevated for project-based potential use of ionizing radiation (OR, 9.6; CI, 1.7 to 55.2) and for potential use of n-hexane lasting at least 4 years (OR, 16.2; CI, 1.1 to 227.6). For benign intracranial tumors, the OR was elevated only for self-reported exposure to ionizing radiation (OR, 5.4; CI, 1.7 to 43.1) and other amines (OR, 5.2; CI, 0.9 to 29.5). Occupational exposure may have contributed to the glioma excess, but the specific causal agents remain unknown. The study indicated that benign intracranial tumors were unlikely to be work-related.     

Mortality among employees at a petrochemical research facility

BACKGROUND: This retrospective follow-up study evaluated mortality during 1970-1996 among 6,956 employees at a petrochemical research facility in Illinois. METHODS: Standardized mortality ratios (SMRs) compared employees' mortality rates with those of the Illinois general population. Poisson regression procedures estimated rate ratios for various subject subgroups compared to other facility employees. RESULTS: Subjects had 267 observed/524 expected deaths (SMR = 51) from all causes combined and a large deficit of deaths from all cancers (76/136, SMR = 56) and from most other major diseases. Other results included fewer than expected brain cancers (1/4.0, SMR = 25) and a slight increase in colorectal cancer (20/14, SMR = 139) that was concentrated in white male scientists employed for one of the three main companies at the facility (SMR = 295, RR = 2.6). CONCLUSIONS: The deficit of brain cancer deaths contrasts with an excess incidence seen in a companion study. Subjects' generally favorable mortality experience probably reflects socioeconomic advantages of employees relative to the Illinois general population.     

Pneumococcal pspA sequence types of prevalent multiresistant pneumococcal strains in the United States and of internationally disseminated clones

In a recent genotypic survey of beta-lactam-resistant pneumococci recovered in different areas of United States during 1997, eight clonal types that each represented 3 to 40 isolates accounted for 134 of 144 isolates (G. Gherardi, C. Whitney, R. Facklam, and B. Beall, J. Infect. Dis. 181:216-229, 2000). We determined the degree of pspA gene diversity among these 134 isolates and for 11 previously characterized internationally disseminated multiresistant strains. Thirty-four different pspA restriction profiles were determined for an amplicon encompassing the variable portion of the structural gene that encodes the surface-exposed domain of PspA and a variable-length proline-rich putative cell wall-associated domain. These restriction profiles closely correlated with those of 33 different pspA sequence types of an approximately 230-residue region corresponding to residues 182 to 410 of the strain Rx1 PspA. These residues encompass a 100-residue clade-defining region known to contain cross-protective epitopes for which 17 sequence types were found. Distinct, conserved pspA sequence types were found for the majority of strains within seven of the eight U.S. clonal types assessed, while one pulsed-field gel electrophoresis type was represented by isolates of three distinct PspA clades. Sequence typing of pspA provides an added level of specificity in the subtyping of isolates and is a necessary first step in determining the components needed in a PspA vaccine which could elicit effective cross-protective coverage.     

Diet and cancer prevention: the fiber first diet

Diet can play a major role in cancer prevention. The international differences in cancer incidence are largely accounted for by lifestyle practices that include nutrition, exercise, and alcohol and tobacco use. About 50% of cancer incidence and 35% of cancer mortality in the U.S., represented by cancers of the breast, prostate, pancreas, ovary, endometrium, and colon, are associated with Western dietary habits. Cancer of the stomach, currently a major disease in the Far East, relates to distinct, specific nutritional elements such as excessive salt intake. For these cancers, information is available on possible initiating genotoxic factors, promoting elements, and prophylactic agents. In general, the typical diet in the United States contains low levels of the potent carcinogenic agents, heterocyclic amines, formed during the cooking of meats. It provides only about half the potent appropriate fiber intake and is high in calories. About twice as many calories as would be desirable come from fat, certain kinds of which enhance the development of cancers. Other foods with functional properties, such as soy products and tea, can be beneficial. To achieve reduction in risk of certain cancers, diet must be optimized, primarily to reduce caloric intake and the fat component. The latter should be 20% or less of total caloric intake and fiber should be increased to 25- 35 g per day for adults. One approach to achieving these goals is the Fiber First Diet, a diet designed around adequate fiber intake from grains, especially cereals, vegetables, legumes, and fruits, which thereby reduces both calorie and fat intake. Such dietary improvements will not only reduce cancer and other chronic disease risks, but will contribute to a healthy life to an advanced age. A corollary benefit is a lower cost of medical care.