Do tobacco companies encourage young people to smoke? Philip Morris does market to young people.
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Biomedical subjects
Publications and source records attributed to J Klein.
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African cichlid fishes are composed of two major lineages, the haplochromines and the tilapiines. Whereas the phylogenetic relationships of the haplochromines have been studied extensively, primarily because of their spectacular adaptive radiations in the Great Lakes of East Africa, little is known about the relationships among the tilapiine species, despite the fact that they have become an important component of African, indeed world, aquaculture. To remedy this situation, molecular phylogenetic analysis of tilapiine fishes was undertaken. A segment of mitochondrial DNA encompassing the terminal part of the tRNA(Pro) gene and the most variable part of the control region was amplified by the polymerase chain reaction with DNA samples isolated from 42 tilapiine species, and the amplification products were subjected to heteroduplex analysis and sequencing. Phylogenetic trees based on 68 sequences revealed the existence of 11 sequence groups and 11 single-sequence branches. The groups, designated Ti1 through Ti11, were distinguished by specific combinations of diagnostic substitutions, formation of monophyletic clusters, and separation by genetic distances in excess of 0.04. Although the relationships among the groups could not be resolved, the sequences separated Oreochromis and Sarotherodon from Tilapia, as defined by Trewavas. The Oreochromis sequences clustered with the Sarotherodon sequences and thus supported the hypothesis that the mouthbrooding behavior of the tilapiine fishes evolved only once from the substrate-spawning behavior. Since on phylogenetic trees the O. alcalicus (sub)species were always separated from O. amphimelas by other Oreochromis species, it was concluded that the adaptation to life in water with a high salt concentration and high pH values evolved independently at least twice in the tilapiine fishes. The tilapiines diverged from the haplochromines more than 8 million years ago; most of the intragroup divergences among the tilapiines took place an estimated 1.1 to 6 million years ago.
In previous studies, major histocompatibility complex (MHC) class II DP, DQ, and DR families of genes were characterized in different primate species mostly on the basis of their second exon sequences. Resemblances were found between Old World monkey (OWM) and New World monkey (NWM) genes and were interpreted as being the result of transspecies evolution. Subsequent analysis of intron sequences of catarrhine and platyrrhine DRB genes, however, revealed that the amplifiable genes were not, in fact, orthologous. To test other DRB genes and other families of the class II region Southern blot hybridizations were carried out with tamarin genomic DNA using probes specific for the third exons of the tamarin DQA, DQB, DPB, and DRB genes. The hybridizing bands were extracted from the gel and the third exons of the genes were amplified by PCR, cloned, and sequenced. With two exceptions, all NWM class II genes were found to group separately from the human sequences. Only the sequences of one nonfunctional DQB locus appeared to be more closely related to human genes than to other platyrrhine DQB genes. In the DRB family one gene was found that grouped with sheep and strepsirhine DRB sequences and might represent an old gene lineage. To extend the sequences to the second exon, long PCRs were performed on tamarin genomic DNA. This approach was successful for five of the ten third exon sequences. From these data, we conclude that at least the functional MHC class II genes have expanded independently in catarrhines and platyrrhines.
Detection and characterization of emboli in the blood stream is of high clinical importance for making decisions after surgery. In this study, a new technique based on the nonlinear oscillations of gas bubbles was applied to gaseous emboli detection, characterization and sizing. To simulate gaseous emboli, an experimental system was developed to produce air bubbles of uniform diameters ranging from 19 microm up to 200 microm. The ultrasonic setup consisted of low-frequency transducers operating at 130 kHz and 250 kHz and using low acoustic pressures (30 kPa and 55 kPa). The experimental and theoretical results show that, depending on the transmitted frequency and the bubble sizes, higher harmonic components were produced in the frequency spectrum of the backscattered echo. Nonresonating bubbles scatter either linearly when their sizes are far away from the resonance size or nonlinearly at the second or third harmonic frequency when their sizes are getting close to the resonance size. Only resonant bubbles or bubbles very close to the resonance size are able to scatter at higher harmonic frequencies (fourth and fifth). This property is used to discriminate resonating bubbles from other bubble sizes. The appearance of harmonic component in the frequency spectrum seems to be an unambiguous tool to differentiate gaseous emboli from solid emboli that scatter linearly.
The present study tests the effects of glucose and choline, the biosynthetic precursors of acetylcholine, on passive avoidance behaviour and hippocampal acetylcholine release measured by microdialysis in awake mice. Glucose (10 and 30mg/kg) or choline chloride (6-60mg/kg), given by i.p. injection immediately after training, dose-dependently enhanced retention in an inhibitory avoidance task. Combinations of low doses of glucose (10mg/kg) and choline chloride (20mg/kg) which alone were submaximally effective significantly increased retention latencies in a synergistic manner, an effect which was sensitive to atropine (0.5mg/kg). This beneficial effect vanished when higher doses of glucose or choline were combined. Basal hippocampal acetylcholine release in mice habituated to their environment was not affected by administration of glucose and choline. However, when hippocampal acetylcholine release was stimulated either by infusion of scopolamine (0.3microM) or by transferring the mice into a novel environment, the combination of glucose plus choline further increased acetylcholine release to a significant extent. We conclude that low doses of glucose and choline act synergistically to improve memory storage, an effect which is due to facilitation of acetylcholine release. This finding reinforces the view that central cholinergic functions are influenced under certain conditions by dietary intake of precursors.
PURPOSE: To determine where adolescents obtain their condoms; the availability and accessibility of condoms; condom availability in relationship to different sexually transmitted disease (STD) rates; and the availability of safer sex information in places where condoms are sold. METHODS: We conducted a random digit-dialed telephone survey of 259 14-19-year-old adolescents in Monroe County, New York. Self-reported health services use, knowledge and use of confidential services, and where adolescents obtained or intended to obtain condoms were assessed. Research assistants visited all retail establishments in five areas of similar population size with gonorrhea rates from 887 to 12,427 per 100,000 adolescents to assess how available and accessible condoms were in each store. Perceived access and actual condom availability and accessibility were compared using Chi-square and Student's t-tests. RESULTS: Trained interviewers dialed 11,800 numbers in 1993, identifying 4449 (40%) households among 11,065 numbers reached successfully. Of these, 393 (8.8%) had eligible adolescents and 259 (66%) completed interviews. Most adolescents reported obtaining, or planning to obtain, condoms in stores rather than from free health care settings. Adolescents who have used condoms more often reported having obtained them without cost than having purchased them. Condoms were available at 101 (83%) of 122 stores identified. All drug stores and 75% of supermarkets sold condoms and displayed them openly. Most small grocery stores also sold condoms (92%), but were less likely to openly display them. No stores displayed or provided safer sex information. Areas with higher STD rates had more stores (p <.01), and more stores that sold condoms (p <.01). There was no difference in condom cost by area. CONCLUSIONS: Many adolescents obtain their condoms in retail stores. Condom accessibility varied by store type and area STD rate. Increasing condom visibility in private grocery stores may increase the accessibility of condoms to adolescents in areas with highest STD rates.
Chronic renal failure is an acknowledged late complication of BMT. It is related to the intensive chemotherapy, radiation and supporting medications. Polymorphism in the angiotensin converting enzyme (ACE) gene is associated with progression of nephropathy caused by diabetes and IgA nephropathy. We sought to determine whether ACE genotype and other clinical factors were associated with loss of renal function after BMT. We determined the genotype of 106 adult allogeneic BMT recipients, who received a similar preparative regimen, survived 1 year, and had assessment of renal function up to 3 years after BMT. We found that the distribution of genotypes was similar to the general population; 29%, 51%, and 20% for the DD, DI, and II genotypes, respectively. There was no statistical difference in patient survival between the three groups. Among all patients, the average creatinine clearance declined from 124 (95% CI 117, 131) to 89 (95% CI 78, 100) ml/min over the 36 months after BMT. Decline in renal function over time was less for patients with the DD compared to the II genotype (P = 0.040). Renal function in patients with the DD genotype was also better than those with the DI genotype, but this was of borderline statistical significance (P = 0.055). Renal shielding reduced decline in renal function compared to no shielding (P = 0.026). We conclude that the ACE genotype does not seem to influence survival, but the DD genotype may be protective against renal injury after BMT. Furthermore, we confirm that renal shielding during TBI reduces the renal injury after BMT.
Preterm birth is the leading cause of infant mortality in industrialised societies. Its incidence is greatly increased among the socially disadvantaged, but the reasons for this excess are unclear and have been relatively unexplored. We hypothesise two distinct sets of causal pathways and mechanisms that may explain social disparities in preterm birth. The first set involves chronic and acute psychosocial stressors, psychological distress caused by those stressors, increased secretion of placental corticotropin releasing hormone (CRH), changes in sexual behaviours or enhanced susceptibility to bacterial vaginosis and chorioamnionitis, cigarette smoking or cocaine use, and decidual vasculopathy. The second hypothesised pathway is a gene-environment interaction based on a highly prevalent mutation in the gene for methylenetetrahydrofolate reductase (MTHFR), combined with low folate intake from the diet and from prenatal vitamin supplements, consequent hyperhomocysteinemia, and decidual vasculopathy. We propose to test these hypothesised pathways and mechanisms in a nested case-control study within a prospectively recruited and followed cohort of pregnant women with singleton pregnancies who deliver at one of four Montreal hospitals that serve an ethnically and socio-economically diverse population. Following recruitment during the late first or early second trimester, participating women are seen at 24-26 weeks, when a research nurse obtains a detailed medical and obstetric history; administers several scales to assess chronic and acute stressors and psychological function; obtains blood samples for CRH, red blood cell and plasma folate, homocysteine, and DNA for the MTHFR mutation; and performs a digital and speculum examination to measure cervical length and vaginal pH and to obtain swabs for bacterial vaginosis and fetal fibronectin. After delivery, each case (delivery at < 37 completed weeks following spontaneous onset of labour or prelabour rupture of membranes) and two controls are selected for placental pathological examination, hair analysis of cotinine, cocaine, and benzoylecgonine, and analysis of stored blood and vaginal specimens. Statistical analysis will be based on multiple logistic regression and structural equation modelling, with sequential construction of models of potential aetiological determinants and covariates to test the hypothesised causal pathways and mechanisms. The research we propose should improve understanding of the factors and processes that mediate social disparities in preterm birth. This improved understanding should help not only in developing strategies to reduce the disparities but also in suggesting preventive interventions applicable across the entire socio-economic spectrum.
Functional proteomics of membrane proteins is an important tool for the understanding of protein networks in biological membranes but structural studies on this part of the proteome are limited. In this study we undertook such an approach to analyse photosynthetic thylakoid membranes isolated from wild-type and mutant strains of Chlamydomonas reinhardtii. Thylakoid membrane proteins were separated by high-resolution two-dimensional gel electrophoresis (2-DE) and analysed by immuno-blotting and mass spectrometry for the presence of membrane-spanning proteins. Our data show that light-harvesting complex proteins (LHCP), that cross the membrane with three transmembrane domains, can be separated using this method. We have identified more than 30 different LHCP spots on our gels. Mass spectrometric analysis of 2-DE separated Lhcb1 indicates that this major LHCII protein can associate with the thylakoid membrane with part of its putative transit sequence. Separation of isolated photosystem I (PSI) complexes by 2-DE revealed the presence of 18 LHCI protein spots. The use of two peptide-specific antibodies directed against LHCI subunits supports the interpretation that some of these spots represent products arising from differential processing and post-translational modifications. In addition our data indicate that the reaction centre subunit of PSI, PsaA, that possesses 11 transmembrane domains, can be separated by 2-DE. Comparison between 2-DE maps from thylakoid membrane proteins isolated from a PSI-deficient (Deltaycf4) and a crd1 mutant, which is conditionally reduced in PSI and LHCI under copper-deficiency, showed the presence of most of the LHCI spots in the former but their absence in the latter. Our data demonstrate that (i) hydrophobic membrane proteins like the LHCPs can be faithfully separated by 2-DE, and (ii) that high-resolution 2-DE facilitates the comparative analysis of membrane protein complexes in wild-type and mutants cells.
Central cholinergic neurotransmission was studied in learning-impaired transgenic mice expressing human acetylcholinesterase (hAChE-Tg). Total catalytic activity of AChE was approximately twofold higher in synaptosomes from hippocampus, striatum and cortex of hAChE-Tg mice as compared with controls (FVB/N mice). Extracellular acetylcholine (ACh) levels in the hippocampus, monitored by microdialysis in the absence or presence of 10(-8)-10(-3) M neostigmine in the perfusion fluid, were indistinguishable in freely moving control and hAChE-Tg mice. Muscarinic receptor functions were unchanged as indicated by similar effects of scopolamine on ACh release and of carbachol on inositol phosphate formation. However, when the mice were anaesthetized with halothane (0.8 vol. %), hippocampal ACh reached significantly lower levels in AChE-Tg mice as compared with controls. Also, the high-affinity choline uptake (HACU) in hippocampal synaptosomes from awake hAChE-Tg mice was accelerated but was reduced by halothane anaesthesia. Moreover, hAChE-Tg mice displayed increased motor activity in novel but not in familiar environment and presented reduced anxiety in the elevated plus-maze test. Systemic application of a low dose of physostigmine (100 microgram/kg i.p.) normalized all of the enhanced parameters in hAChE-Tg mice: spontaneous motor activity, hippocampal ACh efflux and hippocampal HACU, attributing these parameters to the hypocholinergic state due to excessive AChE activity. We conclude that, in hAChE-Tg mice, hippocampal ACh release is up-regulated in response to external stimuli thereby facilitating cholinergic neurotransmission. Such compensatory phenomena most likely play important roles in counteracting functional deficits in mammals with central cholinergic dysfunctions.
A 75-year-old woman presented with general fatigue progressing to somnolence. Laboratory tests showed marked hyponatremia. TSH in the normal range, but low levels of free T3 and free T4. Evaluation of pituitary hormones and magnetic resonance imaging of the pituitary unmasked findings characteristic for hypophysitis with secondary adrenal insufficiency and secondary hypothyroidism. Hormonal substitution with hydrocortisone and levothyroxine resulted in rapid improvement of all symptoms and signs. Without additional treatment shrinkage of the pituitary gland could be documented. Our report extends the known clinical and pathological spectrum of hypophysitis and illustrates the need to include this uncommon entity in the differential diagnosis of hyponatremia even in elderly patients.
Reproductive capacity in women declines dramatically beyond the fourth decade of life. Oocyte quality seems to be the primary determinant of reproductive potential, although age-related uterine changes may also contribute. Underlying reasons for reproductive decline in women remain unclear, and both ovarian and neuroendocrine mechanisms have been proposed.A number of age-related endocrinologic changes precede menopause and predict diminished reproductive capacity. Thus, "ovarian reserve" screening may identify patients in whom attempts at conventional assisted reproduction is warranted before proceeding with ovum donation. Techniques to preserve the maternal genetic contribution to offspring (in lieu of egg donation), including germinal vesicle transfer and donor ooplasm, are under investigation.
INTRODUCTION: Identification of cocaine use based on a urine test may miss many cases because of the short elimination half-life of the drug. Our objective was to verify the sensitivity of the cocaine hair test in admitted users. PATIENTS AND METHODS: Admitted cocaine users (38), that were 18-70 years of age and reported to have refrained from using cocaine in the few days to months prior to the test, were compared to 10 controls who claimed never to have used cocaine. All had negative urine tests for cocaine and benzoylecgonine by thin-layer chromatography. Cocaine and benzoylecgonine were extracted from unwashed hair and tested by established immunoassays. RESULTS: The hair test was positive in 37/38 cases (97%) and in none of the controls. There was significantly more cocaine in black hair than in brown or blonde hair per mg of cocaine dose reported to have been consumed, highlighting a potential bias when interpreting test results in individuals with dark hair. There was a statistically significant correlation between reported dose used and hair concentrations of cocaine. DISCUSSION: The cocaine hair test appears to be highly sensitive and specific in identifying past cocaine use in the setting of a negative urine test.
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Darwin's finches comprise a group of 15 species endemic to the Galápagos (14 species) and Cocos (1 species) Islands in the Pacific Ocean. The group is monophyletic and originated from an ancestral species that reached the Galápagos Archipelago from Central or South America. Descendants of this ancestor on the Archipelago then colonized Cocos Island. In the present study, we used sequences of two mitochondrial (mt) DNA segments (922 bp of the cytochrome b gene and 1,082 bp of the control region), as well as two nuclear markers (830 bp of numt2, consisting of 140 bp of mtDNA control region and 690 bp of flanking nuclear DNA; and 740 bp of numt3, consisting of 420 bp of mt cytochrome b sequence flanked by 320 bp of nuclear DNA) to identify the species group most closely related to the Darwin's finches. To this end, we analyzed the sequences of 28 species representing the main groups (tribes) of the family Fringillidae, as well as 2 outgroup species and 13 species of Darwin's finches. In addition, we used mtDNA cytochrome b sequences of some 180 additional Fringillidae species from the database for phylogeny reconstruction by maximum-parsimony, maximum-likelihood, minimum-evolution, and neighbor-joining methods. The study identifies the grassquit genus Tiaris, and specifically the species Tiaris obscura, as the nearest living relative of Darwin's finches among the species surveyed. Darwin's finches diverged from the Tiaris group shortly after the various extant species of Tiaris diverged from one another. The initial adaptive radiation of the Tiaris group apparently occurred on the Caribbean islands and then spread to Central and South America, from where the ancestors of Darwin's finches departed for the Galápagos Islands approximately 2.3 MYA, at the time of the dramatic climatic changes associated with the closure of the Panamanian isthmus and the onset of Pleistocene glaciation.
UNLABELLED: Memory for intraoperative events may arise from inadequate anesthesia when the hypnotic state is not continuously monitored. Electroencephalogram bispectral index (BIS) enables monitoring of the hypnotic state and titration of anesthesia to an adequate level (BIS 40 to 60). At this level, preserved memory function has been observed in trauma patients. We investigated memory formation in elective surgical outpatients during target-controlled propofol anesthesia supplemented with alfentanil. While BIS remained between 40 and 60, patients listened to a tape with either familiar instances (exemplars) from two categories (Experimental [E] group, n = 41) or bird sounds (Control [C] group, n = 41). After recovery, memory was tested directly and indirectly. BIS during audio presentation was on average (+/- SD) 44 +/- 5 and 46 +/- 5 for Groups E and C, respectively. No patient consciously recalled the intraoperative period, nor were presented words recognized reliably (Group E, 0.9 +/- 0.8 hits; Group C, 0.8 +/- 0.8 hits) (P = 0.7). When asked to generate category exemplars, Group E named 2.10 +/- 1.0 hits versus 1.98 +/- 1.0 in Group C (P = 0.9). We found no explicit or implicit memory effect of familiar words presented during adequate propofol anesthesia at BIS levels between 40 and 60 in elective surgical patients. IMPLICATIONS: This study suggests that stable levels of adequate hypnosis may prevent information processing and memory formation during general anesthesia and supports the feasibility of electroencephalogram bispectral index as a monitor of adequate anesthesia.
BACKGROUND: Adolescents often do not receive recommended preventive counseling and screening services. Few measures are available to assess health care system performance in this area. OBJECTIVE: Develop a reliable, valid, and feasible method for measuring adherence to consensus guidelines for adolescent preventive counseling and screening services. METHODS: The 45-item Young Adult Health Care Survey (YAHCS) was tested with a diverse group of commercially and publicly insured adolescents enrolled in managed care organizations (n = 4,060). Psychometric, bivariate, and multivariate analyses were conducted to assess the reliability, validity, and patterns of variation in the preventive care measurement scales derived from the YAHCS. RESULTS: YAHCS measurement scales demonstrated strong construct validity (mean factor loading = 0.64) and reliability (mean Cronbach's alpha = 0.77). Average preventive counseling and screening scores ranged from 18.2% for discussing risky behavior topics to 50.4% for discussing diet, weight, and exercise topics. Adolescent demographic, health care use, and payer factors explained a small amount of variation across adolescent scores on YACHS scales (mean R2 = 0.086). Females and older teens were more likely to report private time with providers and counseling and screening on topics related to sex. Overall, the odds of receiving preventive counseling and screening for adolescents who reported having private time with providers, engaging in risky behaviors, or both were higher than for adolescents who did not meet privately or report risky behaviors (private visit OR, 3.60; 95% CI, 2.91-4.47; risky behaviors OR, 2.02; 95% CI, 1.62-2.52). CONCLUSIONS: The YAHCS provides a feasible, reliable, and valid method for assessing adherence to adolescent preventive services guidelines. It differentiates among varied aspects of preventive care provided to adolescents and is promising as a potential measure of health plan and provider quality. Improved performance on the YAHCS would indicate progress toward the achievement of Healthy People 2010 goals.
SUMMARY: Smoking in pregnancy is associated with a well-characterized increase in perinatal risks. Despite their wish to discontinue smoking, some pregnant women cannot stop. To characterize nicotine and cotinine levels in women who could not quit smoking after the first trimester, the authors recruited 19 white women (age 17-41 years) between 14-23 weeks of gestation who could not quit smoking. They started smoking at ages 11-22 years (mean 14.5) and smoked for 17 +/- 6 years. They had their first cigarettes 5-60 minutes after waking up (mean 12). Nicotine levels were compared with those expected in white patients in the general population, and the cotinine levels per cigarette smoked were compared with the population-based values. Sixteen of the 19 women had nicotine levels substantially lower than those expected. The mean level of serum cotinine produced by one cigarette per day was 19.1 +/- 15.8 ng/mL (range 6.1-67). The expected levels in white patients in the general population are 13 +/- 7.7 ng/mL. The data suggest that pregnant women who cannot quit heavy smoking in the second trimester form a selective group with pharmacokinetic predisposition to a high rate of nicotine metabolism.