ATM polymorphisms as risk factors for prostate cancer development

The risk of prostate cancer is known to be elevated in carriers of germline mutations in BRCA2, and possibly also in carriers of BRCA1 and CHEK2 mutations. These genes are components of the ATM-dependent DNA damage signalling pathways. To evaluate the hypothesis that variants in ATM itself might be associated with prostate cancer risk, we genotyped five ATM variants in DNA from 637 prostate cancer patients and 445 controls with no family history of cancer. No significant differences in the frequency of the variant alleles at 5557G>A (D1853N), 5558A>T (D1853V), ivs38-8t>c and ivs38-15g>c were found between the cases and controls. The 3161G (P1054R) variant allele was, however, significantly associated with an increased risk of developing prostate cancer (any G vs CC OR 2.13, 95% CI 1.17-3.87, P=0.016). A lymphoblastoid cell line carrying both the 3161G and the 2572C (858L) variant in the homozygote state shows a cell cycle progression profile after exposure to ionising radiation that is significantly different to that seen in cell lines carrying a wild-type ATM gene. These results provide evidence that the presence of common variants in the ATM gene, may confer an altered cellular phenotype, and that the ATM 3161C>G variant might be associated with prostate cancer risk.     

A serosurvey of hepatitis B virus,hepatitis C virus,human T lymphotropic virus type-1 and syphilis in HIV-1-infected patients in Jamaica

The seroprevalences of hepatitis B virus (HBV), hepatitis C virus (HCV), human T lymphotropic virus type-1 (HTLV-1) and syphyilis were determined in 129 HIV-1-infected patients using commercially prepared reagents. The seroprevalences were HCV, 0% (0/129); HBV, 37% (48/129); HTLV-1, 5% (6/129) and syphilis, 20% (26/129). Fifteen per cent (19/129) of the patients had active/chronic HBV infection. The seroprevalence of HBV was statistically significantly higher in HIV-1 infected men (24/49, 50% versus 17/80, 21%; p = 0.005), while the seroprevalence of syphilis was statistically significantly increased in HIV-1 infected patients in the over-40 age group (10/31, 32% versus 6/53, 11%; p = 0.05). These findings throw the spotlight on HBV infection and syphilis and suggest that these two sexually transmitted infections should be carefully surveyed in patients with HIV/AIDS in Jamaica. It is essential for management protocols in Jamaica to include screening for evidence of these co-infections.     

The effect of dodecyl sulfate on immunoglobulin hapten binding

The instantaneous effect of dodecyl sulfate (DDS), in the mM concn range, on the binding of monovalent hapten by immunoglobulin was examined. Fluorescence measurements were utilized to study the effect of the detergent on sheep antiserum generated against thyroxin (T4) and against methamphetamine. Haptens were conjugated with the thiocyanate derivative of fluorescein in order to determine hapten binding on the basis of increased fluorescence polarization for the fluorescein-thiocarbamyl-hapten adducts (FT4 or FA) bound to immunoglobulin. Incubation of anti-T4-serum with DDS for 1 hr before the addition of FT4 resulted in diminished binding. The effect occurred at DDS concns greater than 0.1 mM and was essentially complete at a DDS conc of 1 mM. A kinetic study demonstrated a two stage process. An initial, rapid stage, with a half time less than 30 sec accounted for a reduction of immunoglobulin binding by 75%. The remaining 25% binding capacity was lost during a second, much slower phase with a half-time of about 11/2 hr. Prior hapten binding inhibited the effect of DDS. The degree of protection from combining site denaturation afforded by prior hapten binding was limited by the dissociation rate of bound hapten. The major, rapid phase was completely and immediately reversible by dilution. Prolonged incubation in DDS resulted in irreversible denaturation. The overall rate of DDS denaturation of the entire immunoglobulin molecule, as revealed by changes in the circular dichroism spectrum of a sheep gamma globulin fraction, was considerably slower than the denaturation rate of the combining site.     

HLA-DRB3*0101 is associated with Graves' disease in Jamaicans

OBJECTIVES: Graves' disease is associated with different human leucocyte antigen (HLA) genes in different populations. This studywasdesigned to examinethe HLA class II associations with Graves' disease in Jamaicans. PATIENTS: One hundred and six Jamaicans with Graves' disease and 104 controls. DESIGN: Oligotyping for HLA-DRB1, DRB3, DQA1 and DQB1 alleles was performed using the polymerase chain reaction sequence specific oligonucleotide probe (PCR-SSOP) technique. RESULTS The frequency of HLA-DRB3 *0101 was increased significantly in the patients compared to controls (38.7% vs. 19.2%; RR = 2.72; Pc < 0.015). The protective alleles for Graves' disease were DRB1 *0901 (0.9% vs. 20.2%; RR = 0.04; Pc < 0.001), DRB1*1001 (0.0% vs. 11%; RR = 0.0%; Pc < 0.01) and DRB4 *0101 (0.0% vs. 12.5%; RR = 0.0; Pc < 0.05). A high female to male ratio of Graves' disease, 25 :1, was observed. Other associated autoimmune diseases were rare and no significant HLA class II associations were found with clinical markers of disease. CONCLUSIONS: Jamaican patients with Graves' disease share the DRB3 *0101 susceptible allele and the DRB4 *01 protective allele but not the susceptible haplotype DRB1 *0301, DRB3*0101, DQA1*0501 with Caucasians.     

Genital Chlamydia trachomatis (serotypes D-K) infection in Jamaican commercial street sex workers.

OBJECTIVES: To determine the prevalence of genital Chlamydia trachomatis infections in commercial street sex workers (CSSW) in Jamaica. METHODS: The prevalence of C trachomatis infection was determined in 129 Jamaican CSSW using the direct fluorescent antibody (DFA) method and the isolation techniques which utilise fluorescent and iodine staining of endocervical cytobrush specimens cultured in McCoy cells. The seroprevalence of C trachomatis in the CSSW was also compared with that in blood donors (n = 435), using the microimmunofluorescence (MIF) test. RESULTS: The DFA detected C trachomatis in 16% (21/129) of the specimens. The prevalence as determined by the iodine and fluorescein stained cultures was 24% (31/129) and 25% (33/129) respectively. The overall prevalence of current chlamydial infection detected by the isolation techniques used was 25% (33/129). As determined by the MIF test, a statistically significantly higher seroprevalence rate of C trachomatis (95%, 61/64) was found in CSSW compared with blood donors (53%, 229/435; OR 22.6; chi 2 = 49.8; p < 0.001). The prevalence of current infection in CSSW as indicated by the isolation of C trachomatis was not influenced by history of previous pelvic inflammatory disease (PID), sexually transmitted disease, or condom use. N gonorrhoeae (9%) and Candida albicans (7%) were found in comparatively low frequencies, while Trichomonas vaginalis (0%) was not found in specimens from the CSSW. CONCLUSIONS: A high seroprevalence rate and a high rate of current infection with C trachomatis occur in Jamaican CSSW. In order to control the spread and prevent the severe clinical complications and sequelae of C trachomatis infection, the diagnosis and treatment in such high risk groups such as CSSW should be optimised.