Screening for cervical cancer in HIV-infected women receiving care in the United States

OBJECTIVE: We examined the sociodemographic, clinical and provider factors associated with screening for cervical cancer among HIV-infected women. METHODS: We studied a national sample representing 43,490 women receiving treatment of HIV infection who completed first follow-up surveys of the HIV Cost and Service Utilization Study (HCSUS). All women were asked, "In the past 12 months, have you had a Pap test?" Women reporting an abnormal Pap test result were asked whether they had been told antibiotics could cure abnormal cells, and whether they were scheduled for another Pap test or for a colposcopy within 3 months. RESULTS: Of the population represented, 81% had had a Pap test in the past 12 months. Women who reported having a gynecologist and primary care physician at the same clinical site were almost twice as likely (odds ratio, 1.9; 95% confidence interval, 1.3-3.0) as other women to report Pap testing. Among women who reported abnormal Pap test results and were not told antibiotics could cure abnormal cells, 95% were scheduled for a repeat Pap test or colposcopy, but 15% of the women had not received their repeat Pap test or colposcopy. CONCLUSION: Although Pap test rates and appropriate referral for abnormal findings were high among HIV-tested women, many women with initially abnormal Pap test results did not actually receive follow-up Pap testing or colposcopy. Providing gynecologic care at the same site as primary HIV care would likely improve delivery of needed gynecologic care for women.     

Influence of vascular endothelial growth factor single nucleotide polymorphisms on tumour development in cutaneous malignant melanoma

Vascular endothelial growth factor (VEGF) is a potent regulator of vasculogenesis and tumour angiogenesis. We have investigated whether the VEGF -2578, -1154, +405 and +936 SNPs and associated haplotypes confer susceptibility to and/or influence prognosis in cutaneous malignant melanoma (CMM) skin cancer. A total of 152 CMM patients and 266 controls were genotyped for VEGF promoter SNPs by ARMS-PCR. Strong linkage disequilibrium between the -2578, -1154 and +405 SNPs was detected (association, rho = 0.488-0.965), but not between these SNPs and SNP +936 (association, rho = 0.004-0.130). No SNPs or three SNP haplotypes (-2578, -1154, +405) were significantly associated with CMM, although a number of non-significant trends were observed. However, the VEGF -1154 AA genotype and -2578, -1154, +405 CAC haplotype were both significantly associated with less advanced (Stage 1) disease (P = 0.03). In addition, the VEGF -1154 AA genotype was associated with thinner primary vertical growth phase tumours (P = 0.002), while VEGF -1154 GG was associated with thicker primary tumours (P = 0.02). These preliminary results indicate that VEGF genotype may influence tumour growth in CMM, possibly via the effects of differential VEGF expression on tumour angiogenesis.     

The mutational specificity of l-nitroso-6-nitropyrene in the lacI gene of Escherichia coli strains deficient in nucleotide excision repair

We have examined the mutational specificity of 1-nitroso-6-nitropyrene(1,6-NONP), an activated metabolite of the carcinogen 1,6-dinitropyrene,in the lacI gene of Escherichia coli strains which are deficientin nucleotide excision repair (strain NR6113,     

Viral load,CD4 percentage,and delayed-type hypersensitivity in subjects receiving the HIY-1 Immunogen and antiviral drug therapy

Two trials of subjects inoculated with the inactivated, gp120-depleted HIV-1 Immunogen are reported. In one study, in which 19 subjects received ZDV and 8 subjects received ddI, treatment with the HIV-1 Immunogen did not affect the pharmacokinetic parameters of the antiviral drugs. In another study, 65 subjects who were previously immunized with the HIV-1 Immunogen over a mean period of 4.0 years (range, 1.2–5.4 years) received inoculations at 0 and 6 months. At some point during this 48-week study, 72% of the subjects (47/65) were receiving antiviral drug therapy. The HIV-1 DNA load in CD4 cells and CD4 percentage were found to be stable over the 48-week period. Delayed-type hypersensitivity to HIV-1 antigens increased after two inoculations with the HIV-1 Immunogen. In these two trials, no serious treatment-related adverse events were documented in the subjects. The two studies presented herein are the first to suggest that an immune-based therapy such as the HIV-1 Immunogen can be combined safely with antiviral drugs, supporting further study to evaluate the clinical utility of this approach.     

Borrelia burgdorferi in ticks (Acari: Ixodidae) from coastal Virginia

Ixodid ticks removed from hosts and from vegetation during March-November 1987 at sites in coastal Virginia and North Carolina were examined for Borrelia burgdorferi. B. burgdorferi was evident in nine (22%) Ixodes cookei Packard removed from rice rats (Oryzomys palustris), a white-footed mouse (Peromyscus leucopus), and raccoons (Procyon lotor); four (6%) Amblyomma americanum (L.) removed from raccoons; and two (3%) Dermacentor variabilis (Say) removed from a raccoon and a rice rat. B. burgdorferi was also detected in Ixodes dentatus Marx removed from a brown thrasher (Toxostoma rufum), a Carolina wren (Thryothoros ludovicianus), and a towhee (Piplio erythrophthalamus); and in Haemaphysalis leporispalustris (Packard) removed from a brown thrasher and a white-throated sparrow (Zonotrichia albicollis) netted at Kiptopeke Beach, Va. Two Ixodes dammini Spielman, Clifford, Piesman & Corwin were collected on Parramore Island; one specimen was examined for spirochetes, and it was infected with B. burgdorferi. No spirochetes were detected in host-seeking A. americanum and Amblyomma maculatum Koch removed from vegetation. The plasma of one P. leucopus and sera obtained from two P. lotor contained antibodies to B. burgdorferi. All infected ticks and the seroreactive hosts were collected from the Eastern Shore of Virginia.     

Standardization of rye-grass pollen (Lolium perenne) extract. An immunochemical and physicochemical assessment of six candidate international reference preparations

Six candidate extracts of Lolium perenne (rye-grass) pollen have been studied in 6 laboratories using a variety of immunochemical and physicochemical techniques. Radioallergosorbent test inhibition, crossed immunoelectrophoresis, crossed radio-immunoelectrophoresis, sodium dodecyl sulphate-polyacrylamide gel electrophoresis combined with immunoblot, thin-layer isoelectric focusing and enzyme-linked immunosorbent assay inhibition were used to evaluate each of the coded extracts. The source materials were also studied for identity and possible contamination by light microscopy. On the basis of these data, the Rye-Grass Working Party recommended to the Steering Committee of the Allergen Standardization Subcommittee of the International Union of Immunological Societies that the extract coded C be chosen as the candidate international reference preparation.     

Hypothalamic control of thyrotrophin secretion

1. By means of the haemagglutination-inhibition technique, it has been possible to measure the plasma and pituitary levels of thyroid-stimulating hormone (TSH) following unilateral and bilateral electrolytic lesions placed in the supraoptic area of the hypothalamus of female rats.

2. Unilateral lesions after 8 and 48 hr caused a temporary decrease in the percentage of circulating TSH followed by a return to normal.

3. Bilateral lesions caused a fall in plasma TSH to a level 41% below normal at 10 days whereas the pituitary level increased 70%.

4. Rats with bilateral symmetrical supraoptic lesions, kept for 3 days at 4° C, had a lower plasma TSH content (23%) and a higher pituitary TSH content (16%) than the sham operated control animals but the levels of pituitary TSH did not show any significant difference (0·100 > P > 0·050).

5. Thyroidectomized rats with bilateral lesions kept at 26° C for 3 days had a much lower plasma TSH (39%) and a slightly higher pituitary TSH as compared to the normal intact animals, suggesting that the hypothalamus also influences the synthesis of TSH in the pituitary.

6. Thyroidectomized rats with bilateral lesions kept at 4° C for 3 days showed both a plasma and pituitary TSH increase compared to controls at 26° C, suggesting that when a higher demand for thyroid function is present the pituitary gland has some autonomy for both secretion and release of TSH. This autonomy appears to be slight, as there was no statistically significant difference between the pituitary TSH levels of the thyroidectomized animals bearing similar supraoptic lesions and exposed to 4 and 26° C.

     

Clamp loading,unloading and intrinsic stability of the PCNA, β and gp45 sliding clamps of human,E. coli and T4 replicases

Background: The high speed and processivity of replicative DNA polymerases reside in a processivity factor which has been shown to be a ring-shaped protein. This protein (‘sliding clamp’) encircles DNA and tethers the catalytic unit to the template. Although in eukaryotic, prokaryotic and bacteriophage-T4 systems, the processivity factors are ring-shaped, they assume different oligomeric states. The Escherichia coli clamp (the β subunit) is active as a dimer while the eukaryotic and T4 phage clamps (PCNA and gp45, respectively) are active as trimers. The clamp can not assemble itself on DNA. Instead, a protein complex known as a clamp loader utilizes ATP to assemble the ring around the primer-template. This study compares properties of the human PCNA clamp with those of E. coli and T4 phage. Results: The PCNA ring is a stable trimer down to a concentration below 100 nm (K_d ≈ 21 nm ). On DNA, the PCNA clamp slides freely and dissociates from DNA slowly (t_1/2 ≈ 24 min). β is more stable in solution (K_d < 60 pm ) and on DNA (t_1/2 ≈ 1 h) than PCNA which may be explained by its simpler oligomeric state. The T4 gp45 clamp is a much less stable trimer than PCNA (K_d ≈ 250 nm ) and requires association with the polymerase to stabilize it on DNA as observed previously. The consequence of this cooperation between clamp and polymerase is that upon finishing a template and dissociation of the polymerase from DNA, the gp45 clamp spontaneously dissociates from DNA without assistance. However, the greater stability of the PCNA and β clamps on DNA necessitates an active process for their removal. The clamp loaders (RF-C and γ complex) were also capable of unloading their respective clamps from DNA in the presence of ATP. Conclusions: The stability of the different clamps in solution correlates with their stability on DNA. Thus, the low stability of the T4 clamp explains the inability to isolate gp45 on DNA. The stability of the PCNA and β clamps predicts they will require an unloading factor to recycle them on and off DNA during replication. The clamp loaders of PCNA and β double as clamp unloaders presumably for the purpose of clamp recycling.