Use of state administrative data sources to study adolescents and young adults with rare conditions.

BACKGROUND: Effective care of young people with rare conditions requires ongoing coordinated medical treatment as well as educational and social support services. However, information on treatment is often lacking due to limited data. South Carolina has a repository of comprehensive health and human service data with which individuals may be tracked across the data systems of multiple state agencies and organizations. OBJECTIVE: To develop a method for studying health care of young persons with rare conditions using this repository. METHODS: We identified individuals aged 15 to 24 years diagnosed during 2000-2010 with Fragile X syndrome (FXS), spina bifida (SB), or muscular dystrophy (MD) using a series of algorithms. ICD-9-CM codes were used to initially identify the cohort from medical billing data. Demographics, medical care, employment, education, and socioeconomic status data were then extracted from linked administrative sources. RESULTS: We identified 1,040 individuals with these rare conditions: 125 with FXS, 695 with SB, and 220 with MD. The vast majority of the cases (95%) were identified in the Medicaid database. Half of the cohort was male, with a higher percentage in the FXS and MD groups. Sixty-two percent of the cohort was enrolled in the last year of high school. Over half of the cohort received support services from the state's disability and special-needs agency; 16% received food assistance. Thirty-eight percent were employed at some point during the study period. Forty-nine individuals with SB and 56 with MD died during the study period. CONCLUSIONS: We used a linked statewide data system to study rare conditions. Strengths include the diversity of information, rigorous identification strategies, and access to longitudinal data. Despite limitations inherent to administrative data, we found that linked state data systems are valuable resources for investigating important public health questions on rare conditions.

Reviews of evidence regarding interventions to increase use of child safety seats.

BACKGROUND: In 1998, nearly 600 child occupants of motor vehicles aged younger than 4 years died in motor vehicle crashes. Yet approximately 29% of children aged 4 years and younger do not ride in appropriate child safety seat restraints, which, when correctly installed and used, reduce the need for hospitalization in this age group by 69% and the risk of death by approximately 70% for infants and by 47% to 54% for toddlers (aged 1 to 4 years). METHODS: The systematic review development team reviewed the scientific evidence of effectiveness for five interventions to increase child safety seat use. For each intervention, changes in the use of child safety seats or injury rates were the outcome measures evaluated to determine the success of the intervention. Database searching was concluded in March 1998. More than 3500 citations were screened; of these citations, 72 met the inclusion criteria for the reviews. RESULTS: The systematic review process identified strong evidence of effectiveness for child safety seat laws and distribution plus education programs. In addition, community-wide information plus enhanced enforcement campaigns and incentive plus education programs had sufficient evidence of effectiveness. Insufficient evidence was identified for education-only programs aimed at parents, young children, healthcare professionals, or law enforcement personnel. CONCLUSIONS: Evidence is available about the effectiveness of four of the five interventions we reviewed. This scientific evidence, along with the accompanying recommendations of the Task Force elsewhere in this supplement, can be a powerful tool for securing the resources and commitment required to implement these strategies.

A conditional form of Bruton's tyrosine kinase is sufficient to activate multiple downstream signaling pathways via PLC Gamma 2 in B cells.

BACKGROUND: Bruton's tyrosine kinase (Btk) is essential for B cell development and function. Mutations of Btk elicit X-linked agammaglobulinemia in humans and X-linked immunodeficiency in the mouse. Btk has been proposed to participate in B cell antigen receptor-induced signaling events leading to activation of phospholipase C-gamma2 (PLCgamma2) and calcium mobilization. However it is unclear whether Btk activation is alone sufficient for these signaling events, and whether Btk can activate additional pathways that do not involve PLCgamma2. To address such issues we have generated Btk:ER, a conditionally active form of the kinase, and expressed it in the PLCgamma2-deficient DT40 B cell line. RESULTS: Activation of Btk:ER was sufficient to induce multiple B cell signaling pathways in PLCgamma2-sufficient DT40 cells. These included tyrosine phosphorylation of PLCgamma2, mobilization of intracellular calcium, activation of extracellular signal-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK) mitogen-activated protein kinase (MAPK) pathways, and apoptosis. In DT40 B cells deficient for PLCgamma2, Btk:ER activation failed to induce the signaling events described above with the consequence that the cells failed to undergo apoptosis. CONCLUSIONS: These data suggest that Btk:ER regulates downstream signaling pathways primarily via PLCgamma2 in B cells. While it is not known whether activated Btk:ER precisely mimics activated Btk, this conditional system will likely facilitate the dissection of the role of Btk and its family members in a variety of biological processes in many different cell types.

Improving access to mammograms through community-based influenza clinics. A quasi-experimental study.

BACKGROUND: It is a national priority to increase breast-cancer screening among women aged > or = 50. Annual influenza clinics may represent an efficient setting in which to promote breast-cancer screening among older women. To our knowledge, this possibility has not previously been explored. OBJECTIVE: To examine whether offering women attending community-based influenza clinics the opportunity to receive a scheduling telephone call from a mammography facility will result in an increase in the number of mammograms performed over a 6-month period. METHODS: We used a quasi-experimental design with 6-month follow-up. A contemporaneous population-based survey provided a further control group for comparison. The sample group consisted of a total of 284 women attending nine community-based influenza clinics in a semirural county in Connecticut. All women were aged > or = 50 and reported no mammogram in the preceding 12 months. All women received informational literature on mammography. Experimental subjects were each asked if a radiology facility chosen by the subject could call her at home to schedule a mammogram. Mammograms performed were determined by hospital record for participants who received a scheduling call from a radiology facility, and by self-report for all other participants. RESULTS: Mammography use following access through influenza clinics was approximately twice that of women attending influenza clinics where access to mammography was not offered. Using three different assumptions regarding participants whose mammography status was unknown, the relative risks ranged between 1.6 and 2.1. For each assumption the results were statistically significant (chi(2)=8.51-12.2; p<0.001). CONCLUSIONS: Linking access to mammography at community-based influenza clinics can significantly increase the use of mammograms among women aged > or = 50. Further studies should seek to confirm these findings and determine the degree to which they can be replicated in a variety of communities. Enhancing preventive health practice through the bundling of services suggests a new strategy to exploit available interventions to improve health.

Immune-complex assays for tyrosine protein kinases.

Tyrosine protein kinases (TPKs) represent a diverse group of enzymes that contribute to cellular signal transduction. The generally low abundance of TPKs, coupled with their rapid activation and deactivation, usually precludes their purification through conventional biochemical means. Using immune-complex protein kinase assays, the presence or absence of a given TPK can be established and an estimation of its functional state obtained. In the Basic Protocol of this unit, TPKs are immunoprecipitated, allowed to autophosphorylate in the presence of labeled ATP, run out on an SDS-PAGE gel, and detected by autoradiography. Alternate protocols are provided for the assessment of the functional state of TPKs by providing a potential substrate along with the labeled ATP in the reaction mixture. In the first alternate protocol, the exogenous substrate is a protein, permitting simultaneous assessment of autophosphorylation and exogenous substrate phosphorylation. The second alternate protocol utilizes a peptide substrate, resulting in a rapid, high-throughput assay that evaluates only exogenous substrate phosphorylation.

Assessment of the effects of tyrosine protein kinase inhibitors.

The tyrosine protein kinases are enzymes that are important in cellular signal transduction. Therefore, inhibition of TPKs provides an important means of investigating and potentially controlling many signaling pathways. The first basic protocol in this unit describes an assay of the inhibitory effects of TPK inhibitors in vitro on a specific TPK that has been immune-precipitated from cell lysates. An assay of the effects of several TPK inhibitors on TPKs in vivo in activated cells is also provided. Although the example used here is a nonreceptor TPK, these protocols can be used to assay the effects of inhibitors on receptor TPKs as well.

Reliability and validity of measures from the Behavioral Risk Factor Surveillance System (BRFSS).

OBJECTIVES: To assess the reliability and validity of measures on the BRFSS, to assist users in evaluating the quality of BRFSS data, and to identify areas for further research. METHODS: Review and summary of reliability and validity studies of measures on the BRFSS and studies of measures that were the same or similar to those on the BRFSS from other surveys. RESULTS: Measures determined to be of high reliability and high validity were current smoker, blood pressure screening, height, weight, and BMI, and several demographic characteristics. Measures of both moderate reliability and validity included when last mammography was received, clinical breast exam, sedentary lifestyle, intense leisure-time physical activity, and fruit and vegetable consumption. Few measures were of low validity and only one measure was determined to be of low reliability. Several other measures were of high or moderate reliability or validity, but not both. The reliability or validity could not be determined for some measures, primarily due to lack of research. CONCLUSIONS: Most questions on the core BRFSS instrument were at least moderately reliable and valid, and many were highly reliable and valid. Additional research is needed for some measures.

State-specific prevalence of selected health behaviors, by race and ethnicity--Behavioral Risk Factor Surveillance System, 1997.

PROBLEM/CONDITION: In the United States, disparities in risks for chronic disease (e.g., diabetes, cardiovascular disease, and cancer) and injury exist among racial and ethnic groups. This report summarizes findings from the 1997 Behavioral Risk Factor Surveillance System (BRFSS) of the distribution of access to health care, health-status indicators, health-risk behaviors, and use of clinical preventive services across five racial and ethnic groups (i.e., whites, blacks, Hispanics, American Indians or Alaska Natives, and Asians or Pacific Islanders) and by state. REPORTING PERIOD COVERED: 1997. DESCRIPTION OF SYSTEM: The BRFSS is a state-based telephone survey of the civilian, noninstitutionalized, adult (i.e., persons aged > or = 18 years) population. In 1997, all 50 states, the District of Columbia, and Puerto Rico participated in the BRFSS. RESULTS: Variations in risk for chronic disease and injury among racial and ethnic groups exist both within states and across states. For example, in Arizona, 11.0% of whites, 26.2% of Hispanics, and 50.5% of American Indians or Alaska Natives reported having no health insurance. Across states, the median percentage of adults who reported not having this insurance ranged from 10.8% for whites to 24.5% for American Indians or Alaska Natives. Other findings are as follows. Blacks, Hispanics, American Indians or Alaska Natives, and Asians or Pacific Islanders were more likely than whites to report poor access to health care (i.e., no health-care coverage and cost as a barrier to obtaining health care). Blacks, Hispanics, and American Indians or Alaska Natives were more likely than whites and Asians or Pacific Islanders to report fair or poor health status, obesity, diabetes, and no leisure-time physical activity. Blacks were substantially more likely than other racial or ethnic groups to report high blood pressure. Among all groups, American Indians or Alaska Natives were the most likely to report cigarette smoking. Except for Asians or Pacific Islanders, the median percentage of adults who reported not always wearing a safety belt while driving or riding in a car was > or = 30%. The Papanicolaou test was the most commonly reported screening measure: > or = 81% of white, black, and Hispanic women with an intact uterine cervix reported having had one in the past 3 years. Among white, black, and Hispanic women aged > or = 50 years, > or = 63% reported having had a mammogram in the past 2 years. Approximately two thirds of white, black, and Hispanic women aged > or = 50 years reported having had both a mammogram and a clinical breast examination in the past 2 years; this behavior was least common among Hispanics and most common among blacks. Screening for colorectal cancer was low among whites, blacks, and Hispanics aged > or = 50 years: in each racial or ethnic group, < or = 20% reported having used a home-kit blood stool test in the past year, and < or = 30% reported having had a sigmoidoscopy within the last 5 years. INTERPRETATION: Differences in median percentages between racial and ethnic groups, as well as between states within each racial and ethnic group, are likely mediated by various factors. According to published literature, socioeconomic factors (e.g., age distribution, educational attainment, employment status, and poverty), lifestyle behaviors (e.g., lack of physical activity, alcohol intake, and cigarette smoking), aspects of the social environment (e.g., educational and economic opportunities, neighborhood and work conditions, and state and local laws enacted to discourage high-risk behaviors), and factors affecting the health-care system (e.g., access to health care, and cost and availability of screening for diseases and health-risk factors) may be associated with these differences. ACTION TAKEN: States will continue to use the BRFSS to collect information about health-risk behaviors among various racial and ethnic groups. (ABSTRACT TRUNCATED)

B cell antigen receptor-induced activation of Akt promotes B cell survival and is dependent on Syk kinase.

Signaling through the B cell Ag receptor (BCR) is a key determinant in the regulation of B cell physiology. Depending on additional factors, such as microenvironment and developmental stage, ligation of the BCR can trigger B lymphocyte activation, proliferation, or apoptosis. The regulatory mechanisms determining B cell apoptosis and survival are not known. Using the chicken B lymphoma cell line DT40 as a model system, we investigated the role of the serine/threonine kinase Akt in B cell activation. While parental DT40 cells undergo apoptosis in response to BCR cross-linking, cells overexpressing Akt show a greatly diminished apoptotic response. By contrast, limiting the activation of Akt, either by inhibiting phosphatidylinositol 3-kinase or by ectopic expression of the phospholipid phosphatase MMAC1, results in a significant increase in the percentage of apoptotic cells after BCR cross-linking. Using various DT40 knockout cell lines, we further demonstrate that the tyrosine kinase Syk is required for Akt activation and that Lyn tyrosine kinase inhibits Akt activation. Taken together, the data demonstrate that Akt plays an important role in B cell survival and that Akt is activated in a Syk-dependent pathway.

State- and sex-specific prevalence of selected characteristics--Behavioral Risk Factor Surveillance System, 1996 and 1997.

PROBLEM/CONDITION: High-risk behaviors (e.g., physical inactivity, cigarette smoking, and drinking and driving) and lack of preventive health care (e.g., screening for cancer) are associated with morbidity and mortality from chronic disease and injury. The Behavioral Risk Factor Surveillance System (BRFSS) collects state-specific information to determine the prevalence of such behaviors and preventive practices. By using the BRFSS, states can gain a better understanding of the factors that have a major affect on the health of their adult populations. The BRFSS is also used to monitor progress toward national health objectives. REPORTING PERIOD COVERED: 1996 and 1997. DESCRIPTION OF SYSTEM: The BRFSS is a state-based telephone survey of the civilian, noninstitutionalized, adult (i.e., persons aged 18 years) population. In both 1996 and 1997, 50 states, the District of Columbia, and the Commonwealth of Puerto Rico participated in the BRFSS. RESULTS: As in previous years, state- and sex-specific variations occurred in the prevalence of high-risk behaviors, awareness of certain medical conditions, use of preventive health services, and health-care coverage. For example, in 1997, the percentage of adults who reported being current cigarette smokers ranged from 13.8% to 30.7% among states (median: 23.2%), and the percentage of adults who reported driving after drinking too much alcohol ranged from 0.6% to 5.3% (median: 1.9%). Binge drinking varied substantially not only by state (range: 6.3%-23.3%; median: 14.5%) but also by sex (men: 22.3%; women: 6.7%). Similarly, the prevalence of overweight varied considerably by sex: 62.2% of men and 44.5% of women were overweight in 1997. INTERPRETATION: The 1996 and 1997 BRFSS data demonstrate that U.S. adults engage in behaviors that are detrimental to their health. The data also demonstrate that many adults are making efforts to prevent chronic disease and injury. The prevalence of certain behaviors and health practices differs between states and between men and women. The reasons for these differences by state and sex are subjects for further analysis, but only through continued surveillance can the areas that need further study be identified. PUBLIC HEALTH ACTIONS: Data from the BRFSS are useful in developing and guiding public health programs and policies. For many states, the BRFSS is the only source of state-level data on behaviors and practices related to chronic disease and injury; therefore, BRFSS data are vital for effective decision-making at the local level. States will continue to use these data to help prevent premature morbidity and mortality among their adult population and to assess progress toward national health objectives.

The MMAC1 tumor suppressor phosphatase inhibits phospholipase C and integrin-linked kinase activity.

Loss of the tumor suppressor MMAC1 has been shown to be involved in breast, prostate and brain cancer. Consistent with its identification as a tumor suppressor, expression of MMAC1 has been demonstrated to reduce cell proliferation, tumorigenicity, and motility as well as affect cell-cell and cell-matrix interactions of malignant human glioma cells. Subsequently, MMAC1 was shown to have lipid phosphatase activity towards PIP3 and protein phosphatase activity against focal adhesion kinase (FAK). The lipid phosphatase activity of MMAC1 results in decreased activation of the PIP3-dependent, anti-apoptotic kinase, AKT. It is thought that this inhibition of AKT culminates with reduced glioma cell proliferation. In contrast, MMAC1's effects on cell motility, cell - cell and cell - matrix interactions are thought to be due to its protein phosphatase activity towards FAK. However, recent studies suggest that the lipid phosphatase activity of MMAC1 correlates with its ability to be a tumor suppressor. The high rate of mutation of MMAC1 in late stage metastatic tumors suggests that effects of MMAC1 on motility, cell - cell and cell - matrix interactions are due to its tumor suppressor activity. Therefore the lipid phosphatase activity of MMAC1 may affect PIP3 dependent signaling pathways and result in reduced motility and altered cell - cell and cell - matrix interactions. We demonstrate here that expression of MMAC1 in human glioma cells reduced intracellular levels of inositol trisphosphate and inhibited extracellular Ca2+ influx, suggesting that MMAC1 affects the phospholipase C signaling pathway. In addition, we show that MMAC1 expression inhibits integrin-linked kinase activity. Furthermore, we show that these effects require the catalytic activity of MMAC1. Our data thus provide a link of MMAC1 to PIP3 dependent signaling pathways that regulate cell - matrix and cell - cell interactions as well as motility. Lastly, we demonstrate that AKT3, an isoform of AKT highly expressed in the brain, is also a target for MMAC1 repression. These data suggest an important role for AKT3 in glioblastoma multiforme. We therefore propose that repression of multiple PIP3 dependent signaling pathways may be required for MMAC1 to act as a tumor suppressor.

Deep vein thrombosis as a complication of megestrol acetate therapy among nursing home residents.

OBJECTIVES: To describe a cluster of cases of proximal deep vein thrombosis among nursing home residents treated with megestrol acetate, to identify other risk factors for deep vein thrombosis development among these patients, and to alert physicians to this potential complication of megestrol acetate therapy. DESIGN: Retrospective review. SETTING: A 129-bed Maryland nursing home. PARTICIPANTS: Nineteen residents prescribed megestrol acetate between November 1997 July 1998, identified by computerized pharmacy records. MEASUREMENTS: Demographic data (including identification of known risk factors for deep vein thrombosis development) were collected along with information on the indications for megestrol acetate therapy and its duration, diagnostic studies related to detection of deep vein thrombosis and their results, and patient outcomes following diagnosis of deep vein thrombosis. RESULTS: Megestrol acetate was prescribed for 18 nutritionally at-risk patients and one with uterine cancer. Six (32%) patients developed deep vein thrombosis signs and symptoms, and all diagnoses were confirmed as proximal deep vein thromboses with Doppler studies. (No diagnosis of deep vein thrombosis were made among any nursing home patients not being treated with megestrol acetate during the observation period.) All patients diagnosed with deep vein thrombosis were hospitalized and anticoagulated, but none were diagnosed with pulmonary embolus or died. The length [median (range)] of megestrol acetate treatment was similar regardless of whether deep vein thrombosis developed [117 (57-244) versus 143 (2-294) days, respectively, P = 0.83]. Stratification by length of treatment in 50-day increments revealed that most patients who developed deep vein thrombosis did so after 50 days of treatment (P = 0.046). CONCLUSION: A high incidence of deep vein thrombosis was identified among nursing home residents treated with megestrol acetate, even among ambulatory individuals with no other known risk factors. Because the efficacy of megestrol acetate treatment in nursing home residents with weight loss is unproven, the risk of deep vein thrombosis must be considered when prescribing megestrol acetate, and its use to treat nutritionally at-risk nursing home residents should be limited.

A comparison of driver- and passenger-based estimates of alcohol-impaired driving.

INTRODUCTION: Persons who drive after drinking or ride with drinking drivers are at increased risk of motor vehicle crash. Although alcohol is involved in 40% of fatal motor vehicle crashes yearly, there exist few systems to monitor alcohol-impaired driving. In this study we compare driver- and passenger-based estimates of the prevalence of alcohol-impaired driving. DESIGN: A random-digit-dialing telephone survey of the United States. Participants were adults aged 18 or older who were English- or Spanish-speaking from 5238 households (response rate = 56.1%). RESULTS: From the 4603 respondents who reported driving in the preceding 30 days, we estimate that there were 126 million drinking-driving episodes in the United States in 1994. From the 4380 passengers in the preceding 30 days, we estimate 191 million episodes. Three percent of respondents self-reported as drinking drivers (4.8% of males and 1.3% of females) and 4.9% as passengers of drinking drivers. Drinking drivers were more likely to be passengers of drinking drivers (44% versus 4% of nondrinking drivers). Drinking drivers were also more than twice as likely to report drinking daily, and only one half as likely to report always wearing their safety belts. CONCLUSION: Passengers who report riding with a drinking driver may provide an important estimate of the prevalence of drinking driving. Passengers of drinking drivers represent a high-risk group that is not considered in most prevention efforts. Because being a passenger of a drinking driver is not illegal, it may be an easier topic for clinicians to broach than drinking and driving.

Health care coverage and use of preventive services among the near elderly in the United States.

OBJECTIVES: It has been proposed that individuals aged 55 to 64 years be allowed to buy into Medicare. This group is more likely than younger adults to have marginal health status, to be separating from the workforce, to face high premiums, and to risk financial hardship from major medical illness. The present study examined prevalence of health insurance coverage by demographic characteristics and examined how lack of insurance may affect use of preventive health services. METHODS: Data were obtained from the Behavioral Risk Factor Surveillance System, an ongoing telephone survey of adults conducted by the 50 states and the District of Columbia. RESULTS: Many near-elderly adults least likely to have health care coverage were Black or Hispanic, had less than a high school education and incomes less than $15,000 per year, and were unemployed or self-employed. Health insurance coverage was associated with increased use of clinical preventive services even when sex, race/ethnicity, marital status, and educational level were controlled. CONCLUSIONS: Many near-elderly individuals without insurance will probably not be able to participate in a Medicare buy-in unless it is subsidized in some way.

Identification and characterization of a myristylated and palmitylated serine/threonine protein kinase.

We report the molecular cloning and initial characterization of a novel fatty acid acylated serine/threonine protein kinase. The putative open reading frame is predicted to encode a 305 amino acid protein possessing a carboxy-terminal protein kinase domain and amino-terminal myristylation and palmitylation sites. The protein kinase has been accordingly denoted as the myristylated and palmitylated serine/threonine protein kinase (MPSK). Human and mouse MPSKs share approximately 93% identity at the amino acid level with complete retention of acylation sites. Radiation hybridization localized the human MPSK gene to chromosome 2q34-37. Northern analysis demonstrated that the human MPSK 1.7 kilobase mRNA is widely distributed. Epitope tagged human MPSK was found to be acylated by myristic acid at glycine residue 2 and by palmitic acid at cysteines 6 and/or 8. Palmitylation of MPSK in these experiments was found to require an intact myristylation site. While epitope tagged MPSK in immune complexes or purified human glutathione S transferase-MPSK was found to autophosphorylate at one or more threonine residues, the enzyme was not found to phosphorylate several other common exogenous substrates. Indeed, only PHAS-I was identified as an exogenous substrate which was found to be phosphorylated on threonine and serine residues.

Reconstitution of Btk signaling by the atypical tec family tyrosine kinases Bmx and Txk.

Bruton's tyrosine kinase (Btk) is mutated in X-linked agammaglobulinemia patients and plays an essential role in B cell receptor signal transduction. Btk is a member of the Tec family of nonreceptor protein-tyrosine kinases that includes Bmx, Itk, Tec, and Txk. Cell lines deficient for Btk are impaired in phospholipase C-gamma2 (PLCgamma2)-dependent signaling. Itk and Tec have recently been shown to reconstitute PLCgamma2-dependent signaling in Btk-deficient human cells, but it is not known whether the atypical Tec family members, Bmx and Txk, can reconstitute function. Here we reconstitute Btk-deficient DT40 B cells with Bmx and Txk to compare their function with other Tec kinases. We show that in common with Itk and Tec, Bmx reconstituted PLCgamma2-dependent responses including calcium mobilization, extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) activation, and apoptosis. Txk also restored PLCgamma2/calcium signaling but, unlike other Tec kinases, functioned in a phosphatidylinositol 3-kinase-independent manner and failed to reconstitute apoptosis. These results are consistent with a common role for Tec kinases as amplifiers of PLCgamma2-dependent signal transduction, but suggest that the pleckstrin homology domain of Tec kinases, absent in Txk, is essential for apoptosis.

Paired immunoglobulin-like receptor B (PIR-B) inhibits BCR-induced activation of Syk and Btk by SHP-1.

Coligation of paired immunoglobulin-like receptor B (PIR-B) with B cell antigen receptor (BCR) blocks antigen-induced B cell activation. This inhibition is mediated in part by recruitment of SHP-1 and SHP-2 to the phosphorylated ITIMs in the cytoplasmic domain of PIR-B; however the molecular target(s) of these phosphatases remain elusive. Here we show that PIR-B ligation inhibits the BCR-induced tyrosine phosphorylation of Igalpha/Igbeta, Syk, Btk and phospholipase C (PLC)-gamma2. Overexpression of a catalytically inactive form of SHP-1 prevents the PIR-B-mediated inhibition of tyrosine phosphorylation of Syk, Btk, and PLC-gamma2. Dephosphorylation of Syk and Btk mediated by SHP-1 leads to a decrease of their kinase activity, which in turn inhibits tyrosine phosphorylation of PLC-gamma2. Furthermore, we define a requirement for Lyn in mediating tyrosine phosphorylation of PIR-B. Based on these results, we propose a model of PIR-B-mediated inhibitory signaling in which coligation of PIR-B and BCR results in phosphorylation of ITIMs by Lyn, subsequent recruitment of SHP-1, and a resulting inhibition of the BCR-induced inositol 1,4,5-trisphosphate generation by dephosphorylation of Syk and Btk.

Transcriptional analysis of the PTEN/MMAC1 pseudogene, psiPTEN.

PTEN/MMAC1 is a recently characterized tumor suppressor. A pseudogene derived from the human PTEN/MMAC1 phosphatase, psiPTEN, has been reported. Recent analysis of the pseudogene revealed conflicting results about the expression of psiPTEN. In this study, we show that the PTEN/MMAC1 pseudogene is actively transcribed in all cells and tissues examined. In some cases, pseudogene transcripts were found to represent as much as 70% of the total PTEN/MMAC1 RNA. As psiPTEN is transcribed, there is a potential for misinterpretation of PTEN/MMAC1 mutations when RT-PCR techniques are used, as well as potential for a psiPTEN-encoded translation product. Although we were unable to detect a pseudogene protein product in the cell lines examined, a baculovirus produced GST pseudogene fusion protein exhibited phosphatase activity comparable to wild type. The results of this study, taken together, indicate the potential complication of PTEN/MMAC1 molecular analysis caused by the expression of psiPTEN.

Phenotypic analysis of human glioma cells expressing the MMAC1 tumor suppressor phosphatase.

MMAC1, also known as PTEN or TEP-1, was recently identified as a gene commonly mutated in a variety of human neoplasias. Sequence analysis revealed that MMAC1 harbored sequences similar to those found in several protein phosphatases. Subsequent studies demonstrated that MMAC1 possessed in vitro enzymatic activity similar to that exhibited by dual specificity phosphatases. To characterize the potential cellular functions of MMAC1, we expressed wild-type and several mutant variants of MMAC1 in the human glioma cell line, U373, that lacks endogenous expression. While expression of wild-type MMAC1 in these cells significantly reduced their growth rate and saturation density, expression of enzymatically inactive MMAC1 significantly enhanced growth in soft agar. Our observations indicate that while wild-type MMAC1 exhibits activities compatible with its proposed role as a tumor suppressor, cellular expression of MMAC1 containing mutations in the catalytic domain may yield protein products that enhance transformation characteristics.

Surveillance for use of preventive health-care services by older adults, 1995-1997.

PROBLEM/CONDITION: In 1995, a total of 55 million persons aged > or =55 years lived in the United States. The members of this large and growing segment of the population are major consumers of health care. Their access to medical and dental preventive services contributes to their likelihood of healthy later years and influences their long-term impact on the health-care delivery system. REPORTING PERIOD: 1995-1997. DESCRIPTION OF SYSTEMS: This report summarizes data from the National Health Interview Survey (NHIS), the state-based Behavioral Risk Factor Surveillance System (BRFSS), and the Medicare Current Beneficiary Study (MCBS) to describe national, regional, and state-specific patterns of access to and use of preventive services among persons aged > or =55 years. RESULTS: During 1995-1997, approximately 90% of persons aged > or =55 years living in the United States reported having a regular source of health-care services. However, only 75%-80% reported receiving a routine checkup during the preceding 2 years. The estimated percentage of persons who reported not being able to receive medical care because of cost was highest for those aged 55-64 years. Within this age group, the percentage was highest among Hispanics (4%) and persons without a high school diploma. Approximately 11% of Medicare beneficiaries reported delaying care be cause of cost or because they had no particular source of care. Percentage estimates varied according to age, race/ethnicity, and sociodemographic status. Approximately 95% of persons aged > or =55 years reported having their blood pressure checked during the preceding 2 years, but only 85%-88% had received a cholesterol evaluation during the preceding 5 years. The percentage of women receiving breast and cervical cancer screening decreased with increasing age, and the percentage of persons aged > or =55 years who had received some form of screening for colorectal cancer was low approximately 25% for fecal occult blood testing (FOBT) and 45% for endoscopy. State-specific rates of compliance with vaccination recommendations among persons aged > or =65 years were higher for influenza vaccine (range: 54%-74%) than for pneumococcal vaccine (range: 32%-59%), and compliance increased with advancing age. State-specific estimates of the percentage of annual dental visits varied 40%-75%, and 41%-88% of persons aged > or =65 years reported not having dental insurance. INTERPRETATION: Access to medical services among adults living in the United States is greater for persons aged > or =65 years, compared with those aged <65 years, presumably because of Medicare coverage. In contrast, use of dental services decreased, despite increased need for preventive and restorative dental care. Although Medicare covers many medical services for older adults, financial, personal, and physical barriers to both medical and dental care create racial, regional, and sociodemographic disparities in health status and use of health services in the United States. PUBLIC HEALTH ACTION: Continued surveillance of access to and use of health services among older adults (i.e., persons aged > or =65 years), as well as among persons aged 55-64 years, will help health-care providers target underserved groups, make Medicare coverage decisions, and develop public health programs to ensure equitable access to services and improve the health of older adults.