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Biomedical subjects

L Rosenberg

Publications and source records attributed to L Rosenberg.

At least 19 recordsLinked to original sources

Bone mineral density and lifetime physical activity in South African women.

We investigated the relation between lifetime physical activity and bone mineral density (BMD) in South African women using data collected in a case-control study of breast cancer in relation to BMD. Subjects (n = 144) were of black African or mixed ancestral origin, and <60 years of age (mean age 42.6 +/- 8.9 years). Cases had newly diagnosed breast cancer (n = 62) and controls were referred for conditions unrelated to BMD or breast cancer (n = 82). Physical activity data consisting of household, occupational and leisure-time activity, and activity for transport, were collected via questionnaire at 4 life stages (epochs), viz. 14-21, 22-34, 35-50, and 50+ years of age. Total energy (MET hrs) and peak strain scores were calculated. Lumbar spine and total proximal femur BMD were measured using dual-energy x-ray absorptiometry. BMD measures were similar between groups, therefore data were combined. BMD measures were unrelated to total lifetime physical activity. However, the major determinants of total proximal femur BMD included age, transport activity including walking and bicycling between the ages of 14 and 21 years, and current weight (adjusted r2 = 0.33, P < 0.0001). The major determinants of lumbar spine BMD included age, household energy expenditure between the ages of 14 and 21 years, and current weight (adjusted r2 = 0.23, P < 0.0001). Total peak bone strain score for activities between 14-21 years of age was also significantly correlated with lumbar spine BMD ( r = 0.18, P < 0.05). Intraclass correlation coefficients to assess tracking of activity through epochs 1, 2, and 3 were high for total energy expenditure (0.96; 95%CI: 0.94-0.97), household (0.98; 95%CI: 0.97-0.99) and occupational activity (0.78; 95%CI: 0.71-0.84) and activity for transport (0.92; 95%CI: 0.89-0.94). These data suggest that walking or activities resulting in impact loading at a young age are associated with higher BMD in later years. In addition, our findings suggest tracking of physical activity over time.

Absorptiometry, Photon↗

Significance of the fragmentation region in ultrarelativistic heavy-ion collisions.

We present measurements of the pseudorapidity distribution of primary charged particles produced in Au+Au collisions at three energies, sqrt[s(NN)]=19.6, 130, and 200 GeV, for a range of collision centrali-ties. The distribution narrows for more central collisions and excess particles are produced at high pseudorapidity in peripheral collisions. For a given centrality, however, the distributions are found to scale with energy according to the "limiting fragmentation" hypothesis. The universal fragmentation region described by this scaling grows in pseudorapidity with increasing collision energy, extending well away from the beam rapidity and covering more than half of the pseudorapidity range over which particles are produced. This approach to a universal limiting curve appears to be a dominant feature of the pseudorapidity distribution and therefore of the total particle production in these collisions.

Journal Article↗

Signals for death and differentiation: a two-step mechanism for in vitro transformation of adult islets of Langerhans to duct epithelial structures.

Phenotypic change of adult pancreatic islets has been implicated in the development of certain pancreatic cancers and in islet transplant failure. The aim of this study was to characterize intracellular events that mediate changes in adult islet phenotype. Using an in vitro islet-to-duct transformation model, canine islets were induced to undergo phenotypic transformation to duct-like epithelial structures through a two-stage process. Stage one was characterized by widespread islet cell apoptosis associated with the formation of cavitary spaces within the islets. During this stage, c-Jun N-terminal regulated kinase (JNK) and caspase-3 activities were elevated, while extracellular signal-regulated kinase (ERK) and Akt activities were decreased. The second stage of the process was characterized by an inversion in the balance in activity between these signal transduction pathways and by a concomitant decrease in apoptosis. The transformed islets were no longer immunoreactive for islet cell hormones, but expressed the duct epithelial cell marker CK-AE1/AE3. In contrast to islet cells, these duct epithelial cells were highly proliferative. To clarify the role of the identified changes in signal transduction events, we performed additional studies using pharmacological inhibitors of enzyme activity and demonstrated that inhibition of JNK and caspase-3 activity prevented cystic transformation. Our results indicate that the balance in signaling activity between ERK/Akt and JNK/caspase-3 appears to be an important regulator of islet cell death and differentiation.

Animals↗

Limited Pap screening associated with reduced risk of cervical cancer in South Africa.

BACKGROUND: We investigated the effect of Pap smear screening on the incidence of invasive cancer of the cervix in the Western Cape, South Africa where screening is limited. METHODS: Data were derived from a case-control study of the association of hormonal contraceptives and invasive cervical cancer. Incident cases (n = 524) of invasive cervical cancer who presented at two tertiary hospitals and controls (n = 1540) series matched for age, race, and place of residence were interviewed. Information on a wide range of variables was collected including whether the women had previously had a Pap smear taken and the number and timing of smears. Odds ratios (OR) and 95% CI were calculated using multiple logistic regression. RESULTS: The OR of cervical cancer was reduced among women who had ever had a smear (OR = 0.3, 95% CI: 0.3-0.4). The OR declined with increasing number of smears to 0.2 for >/=>3 smears (trend P = 0.0003). Among women who had a smear <5 years previously the OR was 0.3, but even if the smear was taken >/=15 years previously the women remained at reduced risk (OR = 0.5). CONCLUSION: The data suggest that even limited Pap smear screening reduces the risk of cervical cancer. Should a screening programme be successfully implemented, the incidence of cervical cancer might be reduced by as much as 70%.

Adult↗

Pseudorapidity and centrality dependence of the collective flow of charged particles in Au+Au collisions at sqrt[s(NN)]=130 GeV.

This paper describes the measurement of collective flow for charged particles in Au+Au collisions at sqrt[s(NN)]=130 GeV using the PHOBOS detector at the Relativistic Heavy Ion Collider (RHIC). The measured azimuthal hit anisotropy is presented over a wide range of pseudorapidity (-5.0<eta<5.3) for the first time at this energy. The result, averaged over momenta and particle species, is observed to reach 7% for peripheral collisions at midrapidity, falling off with centrality and increasing |eta|. These results call into question the common assumption of longitudinal boost invariance over a large region of rapidity in RHIC collisions.

Journal Article↗

Altered islet homeostasis before classic insulitis in BB rats.

Young diabetes-prone BioBreeding (BBdp) rats fed a diabetes-promoting, cereal-based, NIH-07 (NIH) diet have decreased islet area compared with rats fed a diabetes-retardant diet at a time when classic insulitis is minimal. This finding raised the possibility that islet homeostasis in BBdp rats may be abnormal. To investigate this possibility further, comparisons were made between BBdp and BB control (BBc) rats fed a diabetes-promoting NIH diet for 22 days after weaning. Pancreatic sections were fixed in Bouin's solution and evaluated using immunohistochemistry and image analysis by staining with antibodies for islet hormones: insulin, glucagon; cell proliferation markers: PCNA, BrdU; markers of islet neogenesis: PDX-1, cytokeratin 20; apoptosis was assessed by morphological changes and TUNEL staining. Body weight of BBdp rats was significantly smaller than BBc rats. Although the total number of islets was higher in BBdp compared with BBc, both islet and beta-cell fraction were similar. BBdp rats had a lower beta-cell mass than BBc rats, although this was not statistically significant. Alpha-cell fraction and beta-cell size were similar. Apoptotic bodies were rare in beta-cells but more frequent in acinar tissue of BBdp rats. When the day-night cycle was reversed to synchronize the apoptotic process, the number of apoptotic bodies in islets and in acinar cells was increased. Apoptotic bodies and BrdU+ or PCNA+ beta-cells were more frequently encountered in islets of BBdp rats. Although the frequency of CK20+ islets in BBdp rats was not different, CK20+ area fraction was smaller in BBdp. The number of extra-islet insulin+ and glucagon+ clusters (<4 cells) was significantly greater in BBdp rats. These data are consistent with an enhanced compensatory or "repair" process in the pancreas of BBdp rats that attempts to maintain islet cell mass by altering homeostasis through increased islet neogenesis.

Animals↗

Energy dependence of particle multiplicities in central Au+Au collisions.

We present the first measurement of the pseudorapidity density of primary charged particles in Au+Au collisions at root square[s(NN)] = 200 GeV. For the 6% most central collisions, we obtain dN(ch)/d(eta)/(/eta/<1) = 650+/-35(syst). Compared to collisions at root square[s(NN)] = 130 GeV, the highest energy studied previously, an increase by a factor of 1.14+/-0.05 at 90% confidence level, is found. The energy dependence of the pseudorapidity density is discussed in comparison with data from proton-induced collisions and theoretical predictions.

Journal Article↗

Changes in neuronal activation with increasing attention demand in healthy volunteers: an fMRI study.

Several lines of evidence suggest that structures involved in mediating attention differentially respond to increasing processing demand. Investigation of differences in neuronal activation, however, has been complicated by methodological inconsistencies and concomitant discrepancies in degree of difficulty and subject effort between disparate tasks. In this study, we utilized fMRI to compare neural activation patterns associated with two related attention tasks associated with different degrees of processing load while controlling for degree of performance difficulty. Healthy volunteers performed two continuous performance tasks, utilizing an identical pairs paradigm (CPT-IP) and a matched simple number recognition paradigm with degraded stimuli (CPT-DS) during a single fMRI scan. Degree of stimulus resolution degradation in the latter CPT was designed to equalize degree of performance difficulty between the two tasks. CPT-IP and CPT-DS were both associated with activation of frontal, limbic, subcortical, and sensory integratory structures. CPT-IP administration was associated with significantly greater activation of left dorsolateral prefrontal cortex, bilateral posterior temporal cortex, bilateral putamen, and thalamus. This study demonstrates both that differing attention tasks are associated with a high degree of functional overlap and that increasing processing demand is associated with increased activation of specific portions of attentional networks.

Adult↗

Follow-up of a large cohort of Black women.

High retention rates in follow-up studies reduce the potential for biased data due to selective losses. The Black Women's Health Study began in 1995 when 64,500 participants aged 21-69 years enrolled by completing postal health questionnaires. Follow-up is carried out biennially. On the basis of data collected between enrollment and completion of the first follow-up, the authors assessed the usefulness of various follow-up methods and compared the characteristics of respondents, nonrespondents, and women lost to follow-up because of an unknown address. The 1997 questionnaire was completed by 82.8% of the participants. The study population was highly mobile: 56.5% moved at least once, and 1.5% moved at least four times. Moving was associated with younger age: A total of 71.7% of participants aged 21-29 years moved at least once compared with 43.2% of women aged 50-69. The most successful and cost-effective method for eliciting completed questionnaires from participants was sending multiple waves of questionnaires. Telephone calls to nonrespondents were successful but were highly labor intensive. Demographic and health characteristics of the women were similar regardless of which mailing was completed, except that early respondents had higher levels of education. Respondents were more highly educated and older than were nonrespondents and lost subjects but were quite similar in all other characteristics. These data suggest that follow-up of a mobile population of African-American women can be successful.

Adult↗

Charged-particle pseudorapidity density distributions from Au+Au collisions at sqrt[s(NN)]=130 GeV.

The charged-particle pseudorapidity density dN(ch)/d eta has been measured for Au+Au collisions at sqrt[s(NN)] = 130 GeV at RHIC, using the PHOBOS apparatus. The total number of charged particles produced for the 3% most-central Au+Au collisions for /eta/<or=5.4 is found to be 4200+/-470. The evolution of dN(ch)/d eta with centrality is discussed, and compared to model calculations and to data from proton-induced collisions. The data show an enhancement in charged-particle production at midrapidity, while in the fragmentation regions, the results are consistent with expectations from pp and pA scattering.

Journal Article↗

Ratios of charged antiparticles-to-particles near mid-rapidity in Au + Au collisions at sqrt[s(NN)]=130 GeV.

We have measured the ratios of antiparticles to particles for charged pions, kaons, and protons near mid-rapidity in central Au+Au collisions at sqrt[s(NN)] = 130 GeV. We observe / = 1.00+/-0.01(stat)+/-0.02(syst), / = 0.91+/-0.07(stat)+/-0.06(syst), and / = 0.60+/-0.04(stat)+/-0.06(syst). The / and / ratios give a consistent estimate of the baryo-chemical potential mu(B) of 45 MeV, a factor of 5-6 smaller than in central Pb+Pb collisions at sqrt[s(NN)] = 17.2 GeV.

Journal Article↗

Low-dose oral contraceptive use and the risk of myocardial infarction.

BACKGROUND: Studies of oral contraceptives (OCs) containing 50 microg or more of estrogen suggest an increased risk of myocardial infarction (MI) among current users, particularly if they smoke heavily. OBJECTIVE: To assess whether use of the newer lower-dose OCs increases the risk of MI. METHODS: A case-control study was conducted from January 1985 through March 1999 in 75 hospitals in the greater-Boston and greater-Philadelphia areas. Data on OC use and MI risk factors were obtained by interview from 627 women with a nonfatal first MI (cases) and 2947 female hospital controls younger than 45 years. RESULTS: The overall odds ratio (OR) for current OC use relative to never used was 1.3 (95% confidence interval [CI], 0.8-2. 2). The OR was elevated, 2.5 (95% CI, 0.9-7.5), among heavy smokers (>/=25 cigarettes per day) but close to 1.0 among lighter smokers (OR = 0.8) and nonsmokers (OR = 1.3). For current OC use together with heavy smoking relative to nonuse and nonsmoking, the OR was 32 (95 % CI, 12-81), considerably greater than that for heavy smoking alone, 12 (95% CI, 8.6-16). The ORs did not vary according to the type of formulation or the dose of estrogen; there were too few users to assess the new 20-microg preparations. Past OC use was unrelated to risk. CONCLUSION: Current use of low-dose OCs in the United States is unrelated to an increased risk of MI among nonsmokers and light smokers, but users who smoke heavily may be at greatly increased risk.

Adult↗

Signal generation and clarification: use of case-control data.

Case-control surveillance systems are useful for 'signal' generation, i.e., signaling potential previously unidentified adverse effects of drugs. Two systems currently in operation, the Slone Epidemiology Unit's Case-Control Surveillance and the Birth Defects Study, have monitored drug effects since 1976. With extensive information on the diagnoses and covariates, the systems have the capacity to carry out in-depth analyses in which the outcome measure is more specifically defined and in which confounding is controlled, thus reducing the possibility of false alarms.

Case-Control Studies↗

Height and breast cancer risk: results from the Black Women's Health Study (United States).

OBJECTIVES: Numerous studies, but not all, have yielded positive associations between adult height and risk of breast cancer. There are few data on black women. We evaluated adult height in relation to breast cancer in data from the Black Women's Health Study, a prospective cohort study of 64,530 African-American women aged 18-69 years at baseline in 1995. METHODS: A total of 910 cases of breast cancer were analyzed: 700 prevalent cases reported at baseline and 210 incident cases that occurred during the first 2 years of follow-up. A comparison group of controls frequency-matched on 5-year category of birth year was chosen from among participants who had not developed breast cancer. Odds ratios (OR) were calculated for various categories of adult height compared to a reference category of height less than or equal to 61 inches (155 cm), with control for current age, age at menarche, and years of education. RESULTS: Increased height was associated with an increased risk of breast cancer overall (p trend = 0.001); the OR for the highest category of height, > 69 inches (175 cm), was 1.6 (95% confidence interval 1.1-2.3). The association was stronger among premenopausal women and women who had less than 16 years of education. Results were similar for prevalent and incident cases. CONCLUSION: The present findings indicate that height is associated with breast cancer risk in African-American women.

Adolescent↗

Meningomyelocele reconstruction with bilobed flaps.

A new method for the repair of meningomyeloceles is described. After neurosurgical repair and closure of the placode, the soft-tissue deficit is closed using a bilobed flap. The flap is based superiorly and laterally to the area to be covered. The first lobe crosses the midline above the defect, and the second lobe goes up the midline perpendicular to the first lobe. Once in place, the flap provides a tension-free repair; no suture lines overlie the cord closure.

Female↗

Clinical and pathological findings in reexcision of incompletely excised basal cell carcinomas.

In common practice, patients with incompletely excised basal cell carcinomas (BCCs) are referred to elective reexcision. In previous reports, it was observed that tumor cells are found in only 50% of the reexcised specimens. The authors performed a retrospective analysis of a large series of patients to evaluate clinical and pathological findings in patients who underwent reexcision of incompletely excised BCCs. A total of 1,478 BCCs arising in 1,278 patients were excised by plastic surgeons in a plastic and reconstructive surgery department during a 4-year period. In 159 patients (10.8%), the excision was incomplete according to the pathological report. These tumors were defined as an incompletely excised BCCs. One hundred of the 159 patients with incompletely excised BCCs (62.9%) were reoperated. Residual tumor cells were found in 28 of 100 patients (28%) within the pathological specimen of the reexcised tissue (defined as positive reexcision, or +veRE). There was no correlation between +veRE and the age or sex of the patient. Location of the BCCs in the cheeks, eyelids, or ears was associated with a low percent of +veRE (10.0%, 13.3%, and 22.2% respectively). Pathological factors associated with a low percent of +veRE were dermal inflammatory infiltrate in the pathological specimen (p = 0.003) and sun damage pathological changes (p = 0.03), but there was no correlation with the pathological subtype distribution of the tumors. The authors conclude that lack of tumor cells at reexcision of incompletely excised BCCs is associated with location of the tumors in the cheeks, eyelids, and ears, and with pathological findings of dermal inflammatory infiltrates or sun damage changes. The roles of inflammatory and solar changes in the destruction of residual carcinoma cells should be investigated further.

Basal Cell Carcinoma↗

Modulation of JNK and p38 stress activated protein kinases in isolated islets of Langerhans: insulin as an autocrine survival signal.

OBJECTIVE: The objective of this study was to determine the effects of islet isolation and cytokine exposure on e-JUN NH2 terminal kinase (JNK) and p38 activation and whether insulin or the p38 inhibitor PD169316 could modify the response. SUMMARY BACKGROUND DATA: Islet transplantation exposes the cells of the graft to a variety of stressful stimuli that could promote beta-cell death and lead to graft failure. METHODS: Islets from canine (n = 12) and cadaveric human (n = 6) pancreata were isolated and purified. Islets were cultured in CMRL 1066 with and without 100 ng/ml insulin. The response to cytokine stimulation with tumor necrosis factor (TNF)alpha and IL-1 beta and the p38 inhibitor PD169316 was also observed. Islet lysates were analyzed by Western blotting for total and phosphorylated JNK and p38 content. Apoptosis was assessed by TdT-mediated dUTP nick end labeling (TUNEL) assay and by a specific cell death enzyme-linked immunosorbant assay (ELISA). RESULTS: In unstimulated islets, JNK activity was highest immediately following isolation, declining over 3 days to a low baseline level. The activity of p38 was lowest immediately after isolation, increasing progressively with time. The addition of insulin resulted in a more rapid decline in JNK activity, as opposed to p38, which showed no decrease in phosphorylation in response to insulin. In the cytokine stimulation studies, IL-1 beta stimulated p38 activation in a dose dependent manner, while JNK was relatively unaffected. PD169316 (100 microg/ml) was able to inhibit p38 activation in response to the isolation procedure as well as cytokine stimulation. Apoptotic activity was highest 24 hours after isolation, and was significantly reduced when islets were maintained in insulin-supplemented medium. CONCLUSIONS: Inhibition of the stress-activated protein kinase (SAPK) pathways may be important for the maintenance of islet cell survival following islet isolation for transplantation. This study supports an autocrine role of insulin in this process.

Adaptor Proteins, Signal Transducing↗