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Biomedical subjects

J Drummond

Publications and source records attributed to J Drummond.

At least 19 recordsLinked to original sources

Deep Impact: observations from a worldwide Earth-based campaign.

On 4 July 2005, many observatories around the world and in space observed the collision of Deep Impact with comet 9P/Tempel 1 or its aftermath. This was an unprecedented coordinated observational campaign. These data show that (i) there was new material after impact that was compositionally different from that seen before impact; (ii) the ratio of dust mass to gas mass in the ejecta was much larger than before impact; (iii) the new activity did not last more than a few days, and by 9 July the comet's behavior was indistinguishable from its pre-impact behavior; and (iv) there were interesting transient phenomena that may be correlated with cratering physics.

Cosmic Dust↗

HPV 16 antibody prevalence in Jamaica and the United States reflects differences in cervical cancer rates.

Human papillomavirus (HPV) is widely accepted as the primary etiologic agent in the development of cervical cancer. DNA of a particular HPV type, HPV 16, is found in about half of tumors tested. Inconsistent with this causal relationship, however, population-based studies of HPV DNA prevalence have often failed to find high rates of anogenital HPV infection in countries with high cervical cancer rates. To examine this issue, we used serology to compare HPV 16 exposure in healthy volunteer blood donors in the United States (n = 278) and similar subjects from a country with 3-fold higher cervical cancer rates, Jamaica (n = 257). Jamaican sexually transmitted disease (STD) patients (n = 831) were also studied to examine in detail the relation of HPV 16 antibodies with sexual history. Serology was conducted using an ELISA employing HPV 16 virus-like particles (VLPs). Age-adjusted seroprevalence rates were greatest among male (29%) and female (42%) STD patients, intermediate in male (19%) and female (24%) Jamaican blood donors and lowest among male (3%) and female (12%) U.S. blood donors. The higher seroprevalence in women was significant, and prevalence tended to increase with age. In multivariate logistic regression, controlling for age and gender, Jamaican blood donors were 4.2-fold (95% CI 2.4-7.2) and STD patients 8.1-fold (95% CI 5.0-13.2) more likely to have HPV 16 VLP antibodies than U.S. blood donors. Among STD patients, HPV 16 antibodies were associated with lifetime number of sex partners and years of sexual activity, as well as other factors. Our data suggest that HPV 16 VLP antibodies are strongly associated with sexual behavior. Moreover, exposure to HPV 16 appears to be much greater in Jamaica than in the United States, consistent with the high rate of cervical cancer in Jamaica.

Adolescent↗

Biallelic inactivation of hMLH1 by epigenetic gene silencing, a novel mechanism causing human MSI cancers.

Mutations of DNA mismatch repair genes, including the hMLH1 gene, have been linked to human colon and other cancers in which defective DNA repair is evidenced by the associated instability of DNA microsatellite sequences (MSI). Germ-line hMLH1 mutations are causally associated with inherited MSI colon cancer, and somatic mutations are causally associated with sporadic MSI colon cancer. Previously however, we demonstrated that in many sporadic MSI colon cancers hMLH1 and all other DNA mismatch repair genes are wild type. To investigate this class of tumors further, we examined a group of MSI cancer cell lines, most of which were documented as established from antecedent MSI-positive malignant tumors. In five of six such cases we found that hMLH1 protein was absent, even though hMLH1-coding sequences were wild type. In each such case, absence of hMLH1 protein was associated with the methylation of the hMLH1 gene promoter. Furthermore, in each case, treatment with the demethylating agent 5-azacytidine induced expression of the absent hMLH1 protein. Moreover, in single cell clones, hMLH1 expression could be turned on, off, and on again by 5-azacytidine exposure, washout, and reexposure. This epigenetic inactivation of hMLH1 additionally accounted for the silencing of both maternal and paternal tumor hMLH1 alleles, both of which could be reactivated by 5-azacytidine. In summary, substantial numbers of human MSI cancers appear to arise by hMLH1 silencing via an epigenetic mechanism that can inactivate both of the hMLH1 alleles. Promoter methylation is intimately associated with this epigenetic silencing mechanism.

Adaptor Proteins, Signal Transducing↗

Mosaicism for a tandem duplication dup(1)(q12q22) in an 18 year old female.

The clinical features and cytogenetic results of an 18 year old mentally handicapped female found to be a mosaic for a tandem duplication of chromosome 1 (46,XX,dup(1)(q12q22)/46,XX) are reported. The case is compared with the three previously described cases and possible mechanisms for the origin of the duplication are discussed. This patient was not found to have features of Proteus syndrome which was previously reported in a subject mosaic for a tandem duplication involving chromosome (1)(q11q25).

Adolescent↗

Childbirth confidence: validating the Childbirth Self-Efficacy Inventory (CBSEI) in an Australian sample.

This study examined the reliability and validity of the Childbirth Self-Efficacy Inventory (CBSEI) (Lowe 1993) in a sample of 100 Australian women. Consistent with US data, the measure was shown to have high internal consistency. Validity of the instrument was determined by applying self-efficacy theory (Bandura 1982), which predicts that parity should have the largest effect on childbirth self-efficacy, followed by knowledge, then support and finally anxiety. Results revealed that having prior good birth experience and knowledge about childbirth had significant effects on childbirth self-efficacy. A factor analysis was performed to determine whether the original factor structure of this instrument held for Australian women. While outcome expectancies and self-efficacy expectancies emerged as distinct factors, the results showed that Australian women did not differentiate between active and second-stage labour. Rather than the two stages of labour emerging as dimensions of the CBSEI, two externally focused coping strategies were revealed.

Adaptation, Psychological↗

Interlaboratory agreement among results of human papillomavirus type 16 enzyme-linked immunosorbent assays.

Serological assays for measuring antibodies to human papillomavirus type 16 (HPV-16) virus-like particles (VLPs) have become important epidemiologic tools in recent years. However, the interlaboratory replicability of these assays has not been assessed. In this investigation, three laboratories tested a panel of specimens obtained from two different groups: 265 subjects in a vulvar cancer case-control study and 107 healthy volunteer blood donors. Each laboratory used an enzyme-linked immunosorbent assay (ELISA), but no attempt was made to standardize assay procedures among the three laboratories. The data showed good day-to-day intralaboratory replicability in laboratory 1 (correlation coefficient, > or = 0.88) and good intra-assay variability in laboratory 3 (correlation coefficient, > or = 0.93). Interlaboratory correlations, likewise, ranged between 0.61 and 0.80 in both case-control study subjects and healthy blood donors, indicating that ELISA optical density (OD) values between laboratories were linearly related regardless of the population. Kappa coefficients (kappa), based on each laboratory's categorical interpretation of its results (as positive or negative), showed good agreement (kappa, > 0.6) in case-control study subjects and moderate agreement (kappa, > or = 0.4) in blood donors, a population that had few strongly positive sera. When OD values near seropositive cutoffs were treated as indeterminates, there was little discordance between laboratories in either population. The data suggest that each laboratory measured the same humoral immune response and that their HPV-16 VLP ELISAs performed similarly (Pearson correlations). Interlaboratory differences, however, probably due to reagents and procedures, were considerably greater than intralaboratory day-to-day variability. Interlaboratory agreement in determining seropositivity (kappa) could be improved by sharing positive and negative serum controls and by treating marginal results as indeterminate. As part of continuing cooperation to improve interlaboratory agreement, we are preparing bulk serum control specimens to be shared and made available to interested researchers.

Enzyme-Linked Immunosorbent Assay↗

MSH6, a Saccharomyces cerevisiae protein that binds to mismatches as a heterodimer with MSH2.

The process of post-replicative DNA-mismatch repair seems to be highly evolutionarily conserved. In Escherichia coli, DNA mismatches are recognized by the MutS protein. Homologues of the E. coli mutS and mutL mismatch-repair genes have been identified in other prokaryotes, as well as in yeast and mammals. Recombinant Saccharomyces cerevisiae MSH2 (MSH for MutS homologue) and human hMSH2 proteins have been shown to bind to mismatch-containing DNA in vitro. However, the physiological role of hMSH2 is unclear, as shown by the recent finding that the mismatch-binding factor hMutS alpha isolated from extracts of human cells is a heterodimer of hMSH2 and another member of the MSH family, GTBP. It has been reported that S. cerevisiae possesses a mismatch-binding activity, which most probably contains MSH2. We show here that, as in human cells, the S. cerevisiae binding factor is composed of MSH2 and a new functional MutS homologue, MSH6, identified by its homology to GTBP.

Amino Acid Sequence↗

Modulation of murine peritoneal macrophage functions by gastrin.

The effect in vitro of gastrin-17 and gastrin-34 was studied at concentrations from 10(-12) to 10(-6) M on several functions of resting peritoneal macrophages from BALB/c mice: adherence to substrate, mobility (spontaneous and directed by chemical gradient or chemotaxis), and ingestion of inert particles (latex beads) or cells (Candida albicans). Both gastrins, at concentrations from 10(-10) to 10(-8) M, inhibited significantly all functions studied with the exception of adherence, which was increased. A dose-response relationship was observed, with a maximum inhibition of macrophage functions found at 10(-9) M. These peptides induced in murine macrophages a significant increase of cAMP levels at 60 and 120 s. Adenosine, an adenylate cyclase inhibitor, significantly increased the ingestion of latex beads, whereas the combined presence of adenosine and either G-17 or G-34 produced similar values to those of control samples without adenosine or gastrin. These results suggest that gastrin is a negative modulator of several macrophage functions, and that the inhibition of these activities is carried out through an increase of intracellular cAMP levels.

Adenosine↗

Subjective appraisal of infant crying.

How families appraise difficult situations contributes to later adaptive functioning. We have observed in both research and practice that when appraising their infants' crying, mothers often compared their own infants' crying to actual or supposed much worse infants. They typically appraised their infants to be crying less than average infants. This phenomenon, defined in the social psychology literature, is called downward comparison. Secondary analysis of an established data set was used to assess the extent of downward comparison and the identification of excessive crying among a sample of 193 primiparous mothers. Mothers appraised their own infants' crying to be less than that of the expected average infant. Mothers who identified their infants as excessive criers made less robust downward comparisons than did mothers who did not identify their infants as excessive criers. Nursing interventions that focus on supporting mothers' positive appraisal and promoting knowledge of infant behaviors, particularly infant crying, are proposed.

Adult↗

Increased susceptibility to Bacillus thuringiensis associated with pyrethroid resistance in Bovicola (Damalinia) ovis (Phthiraptera Mallophaga: possible role of monooxygenases.

A comparison of the toxicity of Bacillus thuringiensis (Berliner) to pyrethroid-susceptible and -resistant strains of Bovicola (Damalinia) ovis showed that B. thuringiensis and pyrethroid toxicity were inversely related. The B. ovis strain with an apparent monooxygenase-mediated pyrethroid resistance mechanism was significantly more susceptible to B. thuringiensis. Susceptibility to B. thuringiensis in both the pyrethroid-susceptible and -resistant strains was significantly reduced after administration of the monooxygenase inhibitor piperonyl butoxide. Susceptibility to B. thuringiensis in the pyrethroid-susceptible strain was significantly enhanced after administration of a monooxygenase inducer, sodium phenobarbital. These results suggest that monooxygenases may be important in increasing the toxicity of B. thuringiensis against B. ovis. We discuss the potential use of B. thuringiensis to control pyrethroid-resistant lice.

Animals↗

Morbidity of juvenile onset inflammatory bowel disease: effects on education and employment in early adult life.

Seventy young adults (50 with Crohn's disease (CD) and 20 with ulcerative colitis (UC) (from a geographically derived cohort of patients with juvenile onset inflammatory bowel disease were interviewed and examined at a mean of 14 (range 5.2-29.5) years after diagnosis. Details of education and employment were collected as part of a structured clinical interview. Although 57% had had periods of absence from school of two months or more, their school examination pass rates were similar to those of the healthy population. The achievements of CD patients were consistently better than those of the UC group. In 15 patients, relapses of inflammatory bowel disease had adversely affected examination performance or prevented them from sitting school examinations. Extra tuition in hospital had been provided for only four patients, and three others had had privately arranged tuition at home. Fifty per cent proceeded to full time higher education. At the time of review, seven patients were full time students, one was a university research fellow, 47 were in full time and three in part time employment, one was self employed, four were housewives, and only six were involuntarily unemployed. All four unemployed CD patients attributed this to inflammatory bowel disease, but other factors were relevant in the unemployed UC patients. Few had direct evidence of rejection by employers on health grounds, though some did not declare their illness to prospective employers.

Adult↗

HTLV-II infection in Florida Indians.

A significantly increased prevalence of antibodies to human T-cell leukemia virus (HTLV) has been described in several native American populations in the United States and Latin America. Initial virologic studies indicate that HTLV-II is the predominant virus responsible for this antibody pattern. We obtained blood samples from 106 Seminole Indians living on four reservations in Southern Florida. Seropositivity to HTLV-I/II was found in 14 (13.2%) of these individuals. Polymerase chain reaction (PCR) documented HTLV-II and the absence of HTLV-I in 7 of the 9 donors available for follow-up testing of white blood cells. Evaluation of various risk factors excluded blood transfusion or intravenous drug use as an important contributing factor to the HTLV-II seroprevalence rate. These studies support the hypothesis that HTLV-II is endemic in many native American tribes in the Western hemisphere.

Florida↗

The prevalence of antibodies to the human T lymphotropic virus (HTLV) in Ghana, West Africa.

We conducted a population-based serosurvey of urban areas and rural regions of southern Ghana, West Africa. Subjects (3763) of all ages were enrolled from 25 city and village sites and in studies of groups of special interest. "Positive" results were difficult to define because of a high frequency of results that were indeterminate on immunoblotting, the current standard for confirmation of HTLV-I. However, polymerase chain reaction results and HTLV type-specific discriminatory tests proved HTLV-I was present in Ghana. No HTLV-2 positivity was observed. By using strict criteria that considered indeterminate results as negative, the overall prevalence was found to be between 1 and 2% in all areas, with no difference by geographic location. Prevalence rose with age and was higher in adult women than men. However, in substudies of selected populations, we found HTLV prevalence among 124 persons with lymphomas and hematological malignancies was not different from that in the general population. Furthermore, the prevalence in prostitutes was similar to that in the general population and in pregnant women. HTLV-I is present in West Africa, but we were unable to associate HTLV-I seropositivity with malignancy or with prostitution.

Adolescent↗

Detection of early human T-cell lymphotropic virus type I antibody patterns during seroconversion among transfusion recipients.

From a cohort of human T-cell lymphotropic virus type I (HTLV-I) exposed transfusion recipients (N = 71) enrolled in the Jamaican Transfusion Study, 11 were selected for detailed laboratory evaluation. All recipients were followed at monthly intervals for 6 months and then bimonthly up to 1 year for evidence of HTLV-I seroconversion. Without regard to results on screening assays, pretransfusion and posttransfusion samples were tested with two licensed HTLV-1 whole-virus screening enzyme immunoassays (EIAs), recombinant EIAs for antibody against tax (p40x) and p21e envelope, standard whole virus Western blot (WB), WB enhanced with recombinant p21e, and radioimmunoprecipitation assay (RIPA). In the early period posttransfusion, antibody to gag core protein was predominant with anti-p24 generally appearing before anti-p19. Recombinant anti-p21e envelope protein, in EIA and WB format, was frequently the earliest envelope reactivity detected, while anti-gp46 in WB and anti-gp61/68 in RIPA system appeared later. Anti-tax antibodies appeared later in the time course of seroconversion. The whole-virus EIAs were less sensitive than the confirmatory assays. The combination of WB and RIPA or WB enhanced with recombinant p21e appeared equally effective in confirming samples as positive by the Public Health Service two gene group confirmatory algorithm. However, specificity of this assay approach could not be addressed in this study.

Adolescent↗

Aflatoxin production by entomopathogenic isolates of Aspergillus parasiticus and Aspergillus flavus.

Fourteen isolates of Aspergillus parasiticus and 2 isolates of Aspergillus flavus isolated from the mealybug Saccharicoccus sacchari were analyzed for production of aflatoxins B1, B2, G1, and G2 in liquid culture over a 20-day period. Twelve Aspergillus isolates including 11 A. parasiticus and 1 A. flavus produced aflatoxins which were extracted from both the mycelium and culture filtrate. Aflatoxin production was detected at day 3 and was detected continually for up to day 20. Aflatoxin B1 production was greatest between 7 and 10 days and significantly higher quantities were produced by A. flavus compared to A. parasiticus. Aflatoxin production was not a stable trait in 1 A. parasiticus isolate passaged 50 times on agar. In addition to loss of aflatoxin production, an associated loss in sporulation ability was also observed in this passaged isolate, although it did maintain pathogenicity against S. sacchari. An aflatoxin B1 concentration of 0.16 micrograms/mealybug (14.2 micrograms/g wet wt) was detected within the tissues of infected mealybugs 7 days after inoculation. In conclusion, the ability of Aspergillus isolates to produce aflatoxins was not essential to the entomopathogenic activity of this fungus against its host S. sacchari.

Aflatoxins↗