Synthetic peptide vaccines for schistosomiasis.
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Biomedical subjects
Publications and source records attributed to C Dahl.
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Several epidemiological investigations suggest an association between diet and prostatic cancer. The most consistent finding has been a risk-enhancing effect of a diet rich in fat, especially animal fat. There is some evidence that dietary fat acts in late prostatic carcinogenesis by promoting the progression from focal to clinical disease, and that this effect may be due to an influence on the hormonal system. Data on other dietary factors, especially vitamin A and beta-carotene, are equivocal. This is probably partly due to the fact that most of the epidemiological studies have been based on limited dietary information. It is unclear whether the nutritional status influences the development of prostatic cancer, and if so, which anthropometric measurements are associated with an increased risk. Future studies should aim at estimating dietary exposures more precisely than hitherto by using calibrated dietary assessment methods that permit adjustment for total energy intake and combining these with biochemical methods. It will also be important to further investigate relations between diet, nutritional status and the hormonal system.
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Adenylylsulphate (adenosine-5'-phosphosulphate, APS) reductase from the extremely thermophilic sulphate-reducing archaeon Archaeoglobus fulgidus is an iron-sulphur flavoprotein containing one non-covalently bound flavin group, eight non-haem iron and six labile sulphide atoms per molecule. Reevaluation of the enzyme structure revealed the presence of two different subunits with molecular masses of 80 and 18.5 kDa. The subunits are arranged in an alpha 2 beta subunit structure. We have cloned and sequenced a 2.7 kb segment of DNA containing the genes for the alpha and beta subunits, which we designate aprA and aprB, respectively. The two genes are separated by 17 bp and localized in the order aprBA. While a putative promoter could not be identified in the vicinity of aprBA a probable termination signal was found just downstream of the translation stop codon of aprA. The codon usage for aprBA shows strong preferences for G and C in the third codon position. aprA encodes a 73.3 kDa polypeptide, which shows significant overall similarities with the flavoprotein subunits of the succinate dehydrogenases from Escherichia coli and Bacillus subtilis and the corresponding flavoprotein of E. coli fumarate reductase. Part of the homologous peptide stretches could be assigned to domains that are involved in the binding of the substrate or of the FAD prosthetic group. aprB encodes a 17.1 kDa polypeptide representing an iron-sulphur protein, seven cysteine residues of which are arranged in two clusters typical of ligands of the iron-sulphur centres in ([Fe3S4][Fe4S4]) 7-Fe ferredoxins.
This is a double blind study of the analgesic need during extracorporeal shock wave lithotripsy (ESWL) with a 2nd generation lithotriptor (Siemens Lithostar) in 56 patients. A control group of 28 patients received 2 ml saline intravenously and 28 patients received 2 ml (0.1 mg) fentanyl intravenously before the start of treatment. Before ESWL all patients had subcutaneous infiltration with 20 ml lidocaine 1% and suppository naproxen 500 mg. Pain scores according to a visual analog scale (VAS) were recorded after 600 and 1000 shock waves and at the end of treatment. The patients were comparable with regard to age, sex, weight, number of shock waves given and duration of treatment. Pain scores and the need for supplementary analgesics were not significantly different between the two groups. We conclude that routine use of morphine is unnecessary during extracorporeal shock wave lithotripsy with Siemens Lithostar.
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The role of oral contraceptive (OC) use in relation to the risk of cervical neoplasia (squamous cell) was investigated in a population-based case-control study in Denmark of 586 women with histologically verified cervical carcinoma in situ (CIS), 59 women with invasive cervical cancer from Copenhagen, and 614 controls drawn at random from the female population in the study area. Ever use of OCs was associated with an increased crude risk for carcinoma in situ (relative risk [RR] = 1.8, 95 percent confidence interval [CI] = 1.3-2.5). The crude risk in relation to invasive carcinoma was 1.6 (CI = 0.7-3.5). After adjustment for potential confounders (excluding human papillomavirus), the risks were marginally increased, but not statistically significant (CIS: RR = 1.4, CI = 0.9-21: invasive: RR = 1.3, CI = 0.5-3.3). The risk increased with duration of use; compared with never users, the adjusted RR for carcinoma in situ was 1.9 (CI = 1.1-3.1) for women who had used OCs for six to nine years, and 1.7 (CI = 1.0-2.7) for women who used OCs for 10 years or more. This was independent of years since last use since both recent and non-recent long-term users were at an increased risk. This trend in risk with duration did not apply to the same extent to invasive lesions. The observation that the risks related to OC use were found both in women who had ever had a Pap smear and in women who had never been screened previously may speak against detection bias as an important factor.
Second and fourth instars of Culex quinquefasciatus Say and Aedes aegypti (L.) and fourth instars of Culiseta morsitans (Theobald) were fed five size classes of latex particles ranging from 0.56 to 5.75 microns. Each experimental run was done on two size classes of particles mixed in different proportions of 10:90, 50:50, and 90:10. Both the gut contents and the food mixtures were analyzed by flow cytometry, and the particle percentage composition was determined. The null hypothesis that no particle selection existed among instars or species was rejected for all species. Small instars ingested disproportionally more large particles in all suspensions. Cs. morsitans and Cx. quinquefasciatus showed variability in their responses. Ae. aegypti almost always ingested more of the larger particles. Differences in particle size selection were related to head morphology and feeding mode. Under experimental conditions, two parameters influenced particle size selection: the relative amount of small particles offered and the size difference between small and large particles. Flow cytometry analyses are recommended for quantitative studies of field material.
A dissimilatory sulphite reductase was isolated from the extremely thermophilic dissimilatory sulphate-reducing archaeon Archaeoglobus fulgidus. In common with other dissimilatory sulphite reductases thus far characterized, the enzyme has an alpha 2 beta 2-structure and contains sirohaem, non-haem iron atoms and acid labile sulphide. The oxidized enzyme exhibited absorption maxima at 281, 394, 545 and 593 nm with a weak band around 715 nm. We have cloned and sequenced the genes for the alpha and beta subunits of this enzyme, which we designate dsrA and dsrB, respectively. They are contiguous in the order dsrA dsrB and probably comprise an operon, since dsrA is preceded by sequences characteristic of promoters in methanogenic archaea, and dsrB is followed by a sequence resembling termination signals in extremely thermophilic sulphur-dependent archaea. dsrA and dsrB encode 47.4 kDa and 41.7 kDa peptides, which have 25.6% amino acid sequence identity, indicating that they may have arisen by duplication of an ancestral gene. Each deduced peptide contains cysteine clusters resembling those postulated to bind sirohaem-[Fe4S4] complexes in sulphite reductases and nitrite reductases from other species. The dsrB encoded peptide lacks a single cysteine residue in one of the two clusters, suggesting that only the alpha subunit binds a sirohaem-[Fe4S4] complex, and chemical analyses showed the presence of only two sirohaems per alpha 2 beta 2 enzyme molecule. Both deduced peptides also contain an arrangement of cysteine residues characteristic of [Fe4S4] ferredoxins, and chemical analyses were consistent with the presence of six [Fe4S4] clusters per alpha 2 beta 2 enzyme molecule, two of which would be expected to be associated with sirohaem while the other four could bind to the ferredoxin-like sites.
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Cytokine gene expression in tumor-infiltrating lymphocytes (TIL) in frozen-tissue sections of 2 types of human solid tumor--ovarian adenocarcinoma and invasive breast cancer--was examined by in situ hybridization with 35S-labeled cDNA probes for human cytokines. The proportion of cells containing mRNA able to hybridize to the antisense c-DNA probes for interleukin 2 (IL-2), tumor necrosis factor alpha (TNF alpha), interferon gamma (IFN gamma) or receptors for IL-2 (either p55 or p70) was also determined in human normal peripheral lymphoid tissues and inflammatory tissues. Few cells were positive for IL2 and TNF alpha mRNA in reactive human lymph nodes and tonsils. Inflammatory lesions, such as salpingitis or chronic active hepatitis, contained 10-20 times more cells positive for cytokine mRNA than reactive lymphoid tissue. In contrast, tumor-infiltrating lymphocytes (TIL) in the stroma of ovarian carcinomas or most ductal breast tumors only rarely expressed mRNA for TNF alpha, IL2 or IFN gamma. The intensity of mononuclear cell infiltration in these tumors correlated positively with the percentage of cells which expressed mRNA for IL-2, TNF alpha and IL-2R. In those ductal breast carcinomas which contained intracellular or intraductal mucins, up to 30% of lymphoid cells in the tumor stroma were positive for IL-2, TNF alpha, IFN gamma and IL-2R. Thus, strong evidence for local activation of mononuclear cells in situ, exemplified by the expression of genes for cytokines, was obtained only in inflammatory lesions and in mucin-producing breast carcinomas. In most carcinomas studied, few TIL expressed genes for cytokines as measured by in situ hybridization. Thus, human solid tumors appear to differ in their ability to induce gene expression for cytokines in TIL.
Sexual, reproductive and venereal risk factors for cervical neoplasia were investigated in a population-based case-control study of 586 women with histologically verified, cervical squamous-cell carcinoma in situ, and 59 women with invasive squamous-cell cervical cancer, diagnosed from 1985 to 1986 in Copenhagen. Cases were identified from the computerized Danish Cancer Registry. An age-stratified control group (n = 614) was drawn at random from the female population in the study area by means of the Danish Central Population Register. A structured questionnaire was mailed to cases as well as controls. Increasing number of sexual partners exerted a significant effect on the risk both for carcinoma in situ, and invasive cancer, independently of age at first intercourse and other potential confounders. Conversely, the association with early age at first intercourse became statistically insignificant after allowance for other risk factors, although an increasing risk was still observed with decreasing age at sexual debut. Early age at first episode with genital warts was a significant risk factor for carcinoma in situ, perhaps indicating a possible increased susceptibility of the cervix epithelium during adolescence. A history of genital warts was a good predictor of risk for carcinoma in situ, whereas a history of previous gonorrhea was associated with an increased risk for invasive carcinoma. Women with multiple births had a significantly increased adjusted risk, especially for carcinoma in situ, although some association was also observed with invasive cervical cancer. The study supports the hypothesis of cervical neoplasia being a sexually transmitted disease, and that carcinoma in situ and invasive cervical carcinoma, to a high degree, have similar patterns of risk factors.
Evidence is presented for the existence of a serum factor(s) (SF), which inhibits the growth of both the interleukin-2 (IL-2)-dependent cell line CTLL and the 2-day generation of CTL cells. This activity is found in the serum of both nude and euthymic mice and its suppressive effect can be detected about 18 hours after addition to CTLL cultures. The inhibitory activity elutes from a Sepharose 6B gel after the gamma globulin fraction (100-150 kD), and is precipitated by ammonium sulfate at 60 w/v% saturation. IL-3-mediated bone marrow colony formation is not inhibited by SF. It also does not suppress the growth of a panel of different tumor cell lines. The spleen cell responsiveness to both Con A and LPS activation is greatly reduced in the presence of SF. However, binding of radiolabelled IL-2 to CTLL cells was not blocked by SF, although the activity was greatly reduced by absorption to these cells. Our data support the existence of factor(s) in sera that may have a regulatory role on IL-2-mediated functions.
Adenylyl sulfate (APS) reductase, the key enzyme of the dissimilatory sulfate respiration, catalyzes the reduction of APS (the activated form of sulfate) to sulfite with release of AMP. A spectroscopic study was carried out with the APS reductase purified from the extremely thermophilic sulfate-reducing archaebacterium Archaeoglobus fulgidus DSM 4304. Combined ultraviolet/visible spectroscopy and low temperature electron paramagnetic resonance (EPR) studies were used in order to characterize the active centers and the reactivity towards AMP and sulfite of this enzyme. The A. fulgidus APS reductase is an iron-sulfur flavoprotein containing two distinct [4Fe-4S] clusters (Centers I and II) very similar to the homologous enzyme from Desulfovibrio gigas. Center I, which has a high redox potential, is reduced by AMP and sulfite, and Center II has a very negative redox potential.
Possible risk factors for cervical cancer were investigated in 645 women, 20-49 years of age from Copenhagen, with histologically confirmed cervical cancer or carcinoma in situ and in 614 controls drawn at random from the female population of the same area. To study the role of the "male factor", monogamous cases and controls together with their husbands were invited for further examination. This included a personal interview, a blood sample for analysis of herpes simplex virus antibodies, and a penile swab for papillomavirus analysis. In total, 41 case couples and 90 control couples were enrolled (89% and 92% of eligibles, respectively). The most significant risk determinants were a history of genital warts in the male (RR = 17.9 for ever vs. never) and ever having used condoms (RR = 0.2). Other potentially important factors, although not statistically significant, were ever having visited prostitutes (RR = 2.6, p = 0.14), circumcision (RR = 0.3, p = 0.18), and a history of genital warts in the female (RR = 4.6), p = 0.09). Having a husband with a history of multiple sexual partners was also associated with an increased crude risk, but when adjustment was made for husband ever having had genital warts, use of condom, and age, no significant excess risk was observed. Human papillomavirus DNA, which was tested for with ViraPap and ViraType, was detected in one of the controls, and in only 2 case husbands. This study points to the importance of "high-risk males" for the development of cervical cancer in their sexual partner; the results support the infectious nature of the disease.
Thirty women participated in a double-blind randomized cross-over trial of the efficacy of a natural product, the powdered root of ginger (Zingiber officinale), and placebo in hyperemesis gravidarum. Three patients had to be withdrawn. Each woman swallowed capsules containing either 250 mg ginger or lactose q.i.d. during the first 4 days of the treatment period. Interrupted by a 2 days wash-out period the alternative medication was given in the second 4-day period. The severity and relief of symptoms before and after each period were evaluated by two scoring systems. The scores were used for statistical analyses of possible differences. Subjectively assessed, 19 women (70.4%) stated preference to the period in which ginger, as was later disclosed, had been given (P = 0.003). More objectively assessed by relief scores a significantly greater relief of the symptoms was found after ginger treatment compared to placebo (P = 0.035). No side effects were observed. The possible mutagenic and antimutagenic characters of ginger reported in a study of E. coli have not been evaluated with respect to any significance in humans. Powdered root of ginger in daily doses of 1 g during 4 days was better than placebo in diminishing or eliminating the symptoms of hyperemesis gravidarum.
The sexual habits in women aged 20-39 years chosen at random were investigated. A total of 513 women from Copenhagen participated while there were 586 women from Nykøbing Falster and 661 women from Nuuk (Godthåb) in Greenland. The women from Copenhagen replied to a questionnaire investigation while women from the other two regions were interviewed personally. The age of commencement of sexual activity was considerably lower in Godthåb in women of all age groups than in Copenhagen and Nykøbing Falster e.g. the prevalence of women with age on commencement of sexual activity less than or equal to 16 years was 70-80% in Godthåb while the corresponding figures for Copenhagen were 50-60% and for Nykøbing Falster 30-58%. Comparison with previous investigations revealed that the average age at the first coitus showed a tendency to decrease in all three regions during the past 20-30 years. The difference in the age at the first coitus between a provincial town (Nykøbing Falster) and a city (Copenhagen) was present only in the case of women in the oldest age group (35-39 years) and a geographical levelling appears to have occurred in the younger age groups (20-24 years) concerning the age at commencement of sexual activity. Women in Greenland had significantly more partners than women in the two South Danish regions. In Godthåb, the prevalence of women with greater than or equal to 40 partners was thus 22.4% while the prevalences in Copenhagen and Nykøbing Falster were 3.5% and 0.3%, respectively. The prevalences of women with 0-1 partners were 1.7%, 10.7% and 20.4%, respectively in Godthåb, Copenhagen and Nykøbing Falster.