Complete genome sequence of Neisseria meningitidis serogroup B strain MC58.

The 2,272,351-base pair genome of Neisseria meningitidis strain MC58 (serogroup B), a causative agent of meningitis and septicemia, contains 2158 predicted coding regions, 1158 (53.7%) of which were assigned a biological role. Three major islands of horizontal DNA transfer were identified; two of these contain genes encoding proteins involved in pathogenicity, and the third island contains coding sequences only for hypothetical proteins. Insights into the commensal and virulence behavior of N. meningitidis can be gleaned from the genome, in which sequences for structural proteins of the pilus are clustered and several coding regions unique to serogroup B capsular polysaccharide synthesis can be identified. Finally, N. meningitidis contains more genes that undergo phase variation than any pathogen studied to date, a mechanism that controls their expression and contributes to the evasion of the host immune system.

Genome sequence of the radioresistant bacterium Deinococcus radiodurans R1.

The complete genome sequence of the radiation-resistant bacterium Deinococcus radiodurans R1 is composed of two chromosomes (2,648,638 and 412,348 base pairs), a megaplasmid (177,466 base pairs), and a small plasmid (45,704 base pairs), yielding a total genome of 3,284, 156 base pairs. Multiple components distributed on the chromosomes and megaplasmid that contribute to the ability of D. radiodurans to survive under conditions of starvation, oxidative stress, and high amounts of DNA damage were identified. Deinococcus radiodurans represents an organism in which all systems for DNA repair, DNA damage export, desiccation and starvation recovery, and genetic redundancy are present in one cell.

DNA uptake signal sequences in naturally transformable bacteria.

The naturally transformable bacterium Haemophilus influenzae Rd contains 1471 copies of the DNA uptake signal sequence (USS) 5'-AAGTGCGGT in its genome. Neisseria meningitidis contains 1891 copies of the USS sequence 5'-GCCGTCTGAA. The USSs are often found in the base paired stem of transcription terminators.

Pregnancy, breast feeding, and oral contraceptives and the risk of epithelial ovarian cancer.

To quantify the effects of cumulative months of pregnancy, breast feeding, and oral contraceptive use on the risk of developing epithelial ovarian cancer, the authors used data collected for the Cancer and Steroid Hormone Study--a multicenter, population-based, case-control study. Detailed reproductive histories were obtained from 436 women aged 20-54 with epithelial ovarian cancer newly diagnosed between December 1980 and December 1982, and from 3833 women aged 20-54 selected at random from the same geographic areas. Estimated relative risks of epithelial ovarian cancer were 0.6 (95% confidence interval (CI) 0.5-0.8) for women who had ever been pregnant, 0.6 (95% CI 0.5-0.8) for women who had ever breast fed, and 0.5 (95% CI 0.5-0.7) for women who had ever used oral contraceptives. Logistic regression analysis revealed a strong trend in decreasing risk of epithelial ovarian cancer with increasing cumulative months of pregnancy; this effect was less pronounced in women aged 50-54 than in younger women. In contrast, a marked reduction in risk was associated with ever having breast fed or used oral contraceptives, while the decrease in risk from additional months of either of these exposures was less than that for pregnancy.

Epidemiology of pediatric human immunodeficiency virus infection in the United States.

HIV infection is an important cause of morbidity and mortality in the pediatric population. Providers of health care to children need to be aware of the problem and the characteristics of the most affected populations. Early diagnosis of HIV infection is critical for initiating appropriate antiviral therapy and prophylactic treatment for opportunistic infections. Attending to the myriad of social problems these families face is equally important for providing an optimal chance for prolonged survival and a reasonably high quality of life.

Publicly funded HIV counseling and testing in the United States, 1992-1995.

Data are collected and reported through the Centers for Disease Control and Prevention (CDC) Counseling and Testing System (CTS) on episodes of publicly funded counseling and HIV testing in the Unites States. The objective of this analysis is to describe testing data reported from 1992 through 1995. In 1992, 2,689,056 tests were performed, and 55,024 (2.0%) were positive; in 1995, 2,491,434 tests were performed, of which 40,605 (1.6%) were positive. Among tests reported with client-level data, the proportion of tests of men and women at higher risk for HIV infection remained stable or declined; the proportion of tests of persons who had been previously tested increased each year; and in 1995, the proportion of tests that included posttest counseling was 86% for anonymous and 70% for confidential tests. Although information collected through CTS could be improved by changing the system so that individuals could be distinguished from testing episodes, the CTS does provide important monitoring information to local and state health departments.

Epidemiology of pediatric human immunodeficiency virus infection in the United States.

Human Immunodeficiency Virus (HIV) infection is a growing problem for children worldwide. As of 31 December 1992, 4249 children with Acquired Immunodeficiency Syndrome (AIDS) under 13 years of age had been reported to the US Centers for Disease Control and Prevention (CDC). HIV is transmitted to children predominantly from their mothers. Nearly all cases of HIV infection acquired from blood transfusions in the United States occurred before donor-screening practices were implemented in March 1985. In 1991, approximately 7000 HIV-infected women gave birth to a liveborn infant in the United States, for a prevalence of 1.7 per 1000 women. Despite recent advances in prophylactic therapy for opportunistic infections, Pneumocystis carinii pneumonia remains the most common AIDS-defining illness in children in the United States. If these cases are to be prevented, children born to HIV-infected mothers will need to be identified early and monitored appropriately for CD4+ cell counts to determine the need for prophylaxis.

Oral contraceptives and breast, endometrial, and ovarian cancers. The Cancer and Steroid Hormone Study Group, Atlanta Georgia.

PIP: The Cancer and Steroid Hormone Study was designed to minimize certain problems criticized in some previous case-control studies of oral contraceptives (OCs) and gynecological cancer. The largest of its type undertaken thus far, the study included over 4000 women with breast cancer, over 600 with endometrial cancer, and over 500 with ovarian cancer, along with over 4000 controls. The controls were selected from the population in the geographical areas from which the cases were drawn. The study was limited to women 20-54 years. Study enrollment occurred between December 1980 and December 1982 at 8 regional cancer registries participating in the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute (NCI). Investigators at these centers attempted to identify all women 20-54 years of age with newly diagnosed primary breast, endometrial, or ovarian cancer. These women constituted the case group. Controls were women 20-54 years chosen by an established method of telephoning households at random in the geographical regions covered by the participating centers. All controls were interviewed in person. To improve the accuracy of reporting OC and other hormone use, 2 memory aids were used: use of a book of photographs of all OC and other female hormone preparations marketed in the US up to 1980; and use of a calendar to record information for each woman about such major life events as marriages, births, divorces, and deaths. Information on contraception and other reductive events was then recorded around these usually well-remembered milestones. A panel of pathologists reviewed histological specimens for all cases of endometrial and ovarian cancer enrolled in this study and for all cases and controls with a history of benign breast disease for whom a biopsy specimen was available. The major findings with respect to OC use and risk of cancers of the breast, endometrium, and ovary largely confirmed those in previous studies. It was found that a history of OC use appeared to protect against endometrial and ovarian cancer and had no overall effect on the risk of breast cancer. Women who had used OCs for less than 1 year had the same risk of developing endometrial cancer as "never-users." Compared with never-users, women who used OCs for 1-5 years, or for more than 5 years, had a relative risk of 0.4. Women who have ever used combination OCs had about 1/2 the risk of developing ovarian cancer compared to women who have never used them. Compared with women who never used OCs, women who had ever used them had a relative risk of breast cancer of 0.9. There was no appreciable trend in the relative risk of breast cancer by duration of use.^ieng

Role of the two-component signal transduction and the phosphoenolpyruvate: carbohydrate phosphotransferase systems in competence development of Haemophilus influenzae Rd.

Haemophilus influenzae Rd becomes competent for transformation by nutritional downshift or transient anaerobic growth through a process that requires cyclic AMP receptor protein and adenylate cyclase. Insertion mutations in crr or ptsI of the phosphoenolpyruvate:carbohydrate phosphotransferase system lowered transformation frequencies, and the effect was reversed by the addition of cyclic AMP. However, insertions into H. influenzae homologs of two-component signal transduction genes had no effect on competence.

A new transformation-deficient mutant of Haemophilus influenzae Rd with normal DNA uptake.

Haemophilus influenzae Rd is a gram-negative natural transformer. A mutant strain, RJ248, that has normal DNA uptake and translocation but whose transformation frequency is 300 times lower than that of wild-type H. influenzae and whose phage recombination is 8 times lower was isolated. The affected gene, comM, is induced during competence development in wild-type H. influenzae but not in RJ248.

Alcohol consumption and ovarian cancer risk.

To study the influence of alcohol consumption on the risk of ovarian cancer in women under age 55, the authors examined data collected in a multicenter, population-based case-control study--the Centers for Disease Control's Cancer and Steroid Hormone Study. Between August 1981 and December 1982, 433 women 20-54 years of age with newly diagnosed ovarian cancer and 2,915 women 20-54 years of age selected at random from the same geographic areas were asked about their consumption of alcoholic beverages during the previous five years. Women who drank any alcohol during the five-year period had a risk of ovarian cancer of 0.9 (95% confidence interval (CI) = 0.7-1.2) compared with nondrinkers. Risk was not associated with the type of alcoholic beverage consumed, nor were the results affected by controlling for demographic characteristics and oral contraceptive use. Although there was no association between moderate alcohol consumption and ovarian cancer, women who drank more than about 20 drinks per week had a relative risk of ovarian cancer of 0.5 (95% CI = 0.2-0.9) compared with women who did not drink.

Pneumocystis carinii pneumonia among US children with perinatally acquired HIV infection.

OBJECTIVE: To describe epidemiologic characteristics of Pneumocystis carinii pneumonia (PCP) among children with perinatally acquired human immunodeficiency virus (HIV) infection to guide prevention efforts. DESIGN: National acquired immunodeficiency syndrome (AIDS) surveillance of children aged 0 through 12 years, a multisite surveillance study of HIV infection in children aged 0 through 12 years, and the national HIV serosurvey of childbearing women. SETTING: Surveillance conducted by state and local health departments and reported to the Centers for Disease Control and Prevention 1982 through 1992. RESULTS: Pneumocystis carinii pneumonia was reported in 1374 (37%) of 3665 perinatally acquired AIDS cases. Over half of these cases occurred between 3 and 6 months of age. In 183 (64%) of 275 PCP cases reported in the special surveillance study, PCP was the first or only AIDS-defining condition diagnosed, and in 44% of cases, the child had not been evaluated for HIV infection before diagnosis of PCP. The estimated median survival after diagnosis of PCP was 19 months. CONCLUSIONS: Pneumocystis carinii pneumonia is a common and serious opportunistic infection that affects young children with HIV infection. Effective efforts to prevent PCP in this population will require identification as early as possible of children who may be infected with HIV.

In vitro Tn7 mutagenesis of Haemophilus influenzae Rd and characterization of the role of atpA in transformation.

Haemophilus influenzae Rd is a gram-negative bacterium capable of natural DNA transformation. The competent state occurs naturally in late exponential growth or can be induced by a nutritional downshift or by transient anaerobiosis. The genes cya, crp, topA, and sxy (tfoX) are known to function in the regulation of competence development. The phosphoenolpyruvate:carbohydrate phosphotransferase system functions to maintain levels of cyclic AMP necessary for competence development but is not directly involved in regulation. The exact signal(s) for competence and the genes that mediate the signal(s) are still unknown. In an effort to find additional regulatory genes, H. influenzae Rd was mutated by using an in vitro Tn7 system and screened for mutants with a reduced ability to induce the competence-regulatory gene, comA. Insertions in atpA, a gene coding for the alpha subunit of the F1 cytoplasmic domain of the ATP synthase, reduce transformation frequencies about 20-fold and cause a significant reduction in expression of competence-regulatory genes, while the expression of constitutive competence genes is only minimally affected. In addition, we found that an insertion in atpB, which encodes the a subunit of the F0 membrane-spanning domain, has a similar effect on transformation frequencies.

Cigarette smoking and the risk of breast cancer.

The authors examined the relation between cigarette smoking and breast cancer in the Centers for Disease Control Cancer and Steroid Hormone Study, a multicenter, population-based case-control study. The study compared 4,720 women aged 20-54 years with newly diagnosed breast cancer identified through population-based tumor registries with 4,682 women randomly selected from the same geographic areas. Women who reported ever smoking cigarettes had a risk of breast cancer of 1.2 (95 percent confidence interval 1.1-1.3) compared with never smokers. There was no consistent dose-response pattern with any measure of smoking (pack-years of smoking, average number of cigarettes per day, or total years smoked) and little difference in risk between current and former smokers. There was some variation in risk by age, with slightly higher risk estimates for younger women than for older women. Although current smokers had an earlier natural menopause than did never smokers, the authors found no evidence of a protective effect of cigarette smoking on breast cancer risk. These findings suggest that the risk of breast cancer in women who smoke is the same as, or perhaps slightly higher than, women who have never smoked.

Early diagnosis of cystic fibrosis in the newborn period and risk of Pseudomonas aeruginosa acquisition in the first 10 years of life: A registry-based longitudinal study.

OBJECTIVE: Controlled clinical trial data have suggested that identifying asymptomatic cystic fibrosis (CF) patients through newborn screening improves health outcomes of affected children in the first decade of life. However, it is unclear whether these improvements also include a reduction in risk for bronchial infection, the major determinant of CF morbidity. The authors therefore investigated the association between early CF diagnosis and acquisition of Pseudomonas aeruginosa, the major bronchial pathogen, in the first decade of life. METHODOLOGY: Longitudinal data on 3625 CF patients diagnosed between 1982 and 1990 and before 36 months of age were ascertained from the National Cystic Fibrosis Patient Registry. We compared P aeruginosa acquisition in the first 10 years of life among 4 groups: EAD (early asymptomatic diagnosis)-<6 weeks, by pre/neonatal screening, genotype, family history (n = 157); ESD (early symptomatic diagnosis) (n = 227); LAD (late asymptomatic diagnosis)-6 weeks to 36 months (n = 161); and LSD (late symptomatic diagnosis) (n = 3080). P aeruginosa acquisition was determined from yearly sputum and/or bronchoscopy cultures. Children whose CF diagnoses followed meconium ileus or whose cultures were obtained only from nasal samples were excluded from the study. RESULTS: Kaplan Meier analyses for P aeruginosa acquisition were conducted for each diagnostic group. Regression models were used to generate adjusted relative hazards with EAD as the referent group. Relative hazards were 0.9 (95% confidence interval [CI]: 0.7-1.2) for ESD, 0.8 (95% CI: 0.6-1.2) for LAD, and 1.0 (95% CI: 0.7-1.2) for LSD. The risk of acquiring P aeruginosa was therefore not significantly different between children diagnosed early, late, asymptomatically, or symptomatically. CONCLUSIONS: These data suggest that, despite improvements in other health outcomes from newborn screening for CF, early asymptomatic diagnosis of CF does not affect P aeruginosa acquisition.

DNA sequence of both chromosomes of the cholera pathogen Vibrio cholerae.

Here we determine the complete genomic sequence of the gram negative, gamma-Proteobacterium Vibrio cholerae El Tor N16961 to be 4,033,460 base pairs (bp). The genome consists of two circular chromosomes of 2,961,146 bp and 1,072,314 bp that together encode 3,885 open reading frames. The vast majority of recognizable genes for essential cell functions (such as DNA replication, transcription, translation and cell-wall biosynthesis) and pathogenicity (for example, toxins, surface antigens and adhesins) are located on the large chromosome. In contrast, the small chromosome contains a larger fraction (59%) of hypothetical genes compared with the large chromosome (42%), and also contains many more genes that appear to have origins other than the gamma-Proteobacteria. The small chromosome also carries a gene capture system (the integron island) and host 'addiction' genes that are typically found on plasmids; thus, the small chromosome may have originally been a megaplasmid that was captured by an ancestral Vibrio species. The V. cholerae genomic sequence provides a starting point for understanding how a free-living, environmental organism emerged to become a significant human bacterial pathogen.

Evidence for lateral gene transfer between Archaea and bacteria from genome sequence of Thermotoga maritima.

The 1,860,725-base-pair genome of Thermotoga maritima MSB8 contains 1,877 predicted coding regions, 1,014 (54%) of which have functional assignments and 863 (46%) of which are of unknown function. Genome analysis reveals numerous pathways involved in degradation of sugars and plant polysaccharides, and 108 genes that have orthologues only in the genomes of other thermophilic Eubacteria and Archaea. Of the Eubacteria sequenced to date, T. maritima has the highest percentage (24%) of genes that are most similar to archaeal genes. Eighty-one archaeal-like genes are clustered in 15 regions of the T. maritima genome that range in size from 4 to 20 kilobases. Conservation of gene order between T. maritima and Archaea in many of the clustered regions suggests that lateral gene transfer may have occurred between thermophilic Eubacteria and Archaea.

Complete genome sequence of Caulobacter crescentus.

The complete genome sequence of Caulobacter crescentus was determined to be 4,016,942 base pairs in a single circular chromosome encoding 3,767 genes. This organism, which grows in a dilute aquatic environment, coordinates the cell division cycle and multiple cell differentiation events. With the annotated genome sequence, a full description of the genetic network that controls bacterial differentiation, cell growth, and cell cycle progression is within reach. Two-component signal transduction proteins are known to play a significant role in cell cycle progression. Genome analysis revealed that the C. crescentus genome encodes a significantly higher number of these signaling proteins (105) than any bacterial genome sequenced thus far. Another regulatory mechanism involved in cell cycle progression is DNA methylation. The occurrence of the recognition sequence for an essential DNA methylating enzyme that is required for cell cycle regulation is severely limited and shows a bias to intergenic regions. The genome contains multiple clusters of genes encoding proteins essential for survival in a nutrient poor habitat. Included are those involved in chemotaxis, outer membrane channel function, degradation of aromatic ring compounds, and the breakdown of plant-derived carbon sources, in addition to many extracytoplasmic function sigma factors, providing the organism with the ability to respond to a wide range of environmental fluctuations. C. crescentus is, to our knowledge, the first free-living alpha-class proteobacterium to be sequenced and will serve as a foundation for exploring the biology of this group of bacteria, which includes the obligate endosymbiont and human pathogen Rickettsia prowazekii, the plant pathogen Agrobacterium tumefaciens, and the bovine and human pathogen Brucella abortus.