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Biomedical subjects

W E Rawls

Publications and source records attributed to W E Rawls.

At least 37 records · Page 2Linked to original sources
PubMed1989

Invasive cervical cancer and smoking in Latin America.

A case-control study of 667 patients with invasive squamous cell carcinoma of the cervix and 1,430 controls from four Latin American countries showed an age-adjusted relative risk (RR) of 1.2 [95% confidence interval (CI) = 1.0-1.4] for women who had ever smoked, with risk rising to 1.7 (95% CI, 0.8-3.6) for women who smoked greater than or equal to 30 cigarettes per day. The associations were practically eliminated after adjustment for the number of sexual partners and alcohol consumption, probably a surrogate for an unidentified life-style risk factor. Some excess risk persisted among women who smoked for extended periods (RR = 1.5 for greater than or equal to 40 yr), as well as those who began smoking at older ages (RR = 1.7 for greater than 30 yr), which suggests a late-stage effect. In addition, among women who tested positive for human papillomavirus (HPV) type 16 or 18 by filter in situ hybridization, there was an increased risk for women who had ever smoked and a dose-response relationship with the number of cigarettes smoked (adjusted RRs compared with HPV-negative nonsmokers = 5.0 for HPV-positive nonsmokers, 5.5 for less than 10 cigarettes/day, and 8.4 for greater than or equal to 10 cigarettes/day). In contrast, HPV-negative women had no increased risk associated with smoking. These results, from a high-incidence area where intensive smoking among women is still relatively rare, suggest that smoking has a limited effect on cervical cancer risk, possibly only among women with specific types of HPV.

Age Factors↗
PubMed1989

Genital human papillomavirus infection in Panama City prostitutes.

Little is known of the natural history of genital human papillomavirus (HPV) infections in women from high-risk populations. Samples were collected from 183 Panama City prostitutes and assessed for HPV (filter in situ DNA hybridization) and for sexually transmitted agents. The cohort was followed for 8 mo; 51% of subjects completed four monthly return visits and 16% were sampled eight times. The proportion of women found infected with HPV increased significantly with increasing numbers of consecutive samples tested; 38 (21%) of 183 women were positive after one visit and 46 (82%) of 56 who completed six visits were infected. The pattern of viral detection over time was not random, which implied that most prostitutes were persistently infected with genital HPVs and that either scattered foci of infection or periodic reactivation of latent virus occurred. Our findings suggest that multiple sampling is necessary to accurately estimate HPV infection rates and to define whether patterns of DNA expression are present.

Adolescent↗
PubMed1989

Parity as a risk factor for cervical cancer.

In a case-control study of 759 invasive cervical cancer patients and 1,430 controls in Colombia, Costa Rica, Mexico, and Panama conducted during 1986-1987, an association with number of pregnancies persisted after adjustment for sexual and socioeconomic variables. Risks rose steadily to 5.1 (95% confidence interval 2.7-9.7) for those with 14 or more pregnancies and a relation of risk to multiparity was observed in all four study countries. Pregnancy associations appeared to relate to the number of live births rather than to miscarriages or abortions, with multiparity relations most pronounced among premenopausal women and oral contraceptive users. Human papillomaviruses types 16 and 18, as measured by filter in situ hybridization, were not significantly associated with number of births and did not explain the strong relation of parity to risk. Our results indicate the need for further consideration of reproductive factors on cervical cancer risk, with attention given to possible mechanisms of action, including hormonal factors and cervical trauma.

Adult↗
PubMed1987

Association of reduced interleukin-2 production with genetic susceptibility to Pichinde virus in inbred strains of hamsters.

Adult inbred MHA hamsters are susceptible to lethal infections with Pichinde virus while inbred LSH hamsters resist such infections. Previous studies demonstrated higher levels of endogenous and induced natural killer (NK) activity in MHA splenocytes than in LSH splenocytes. Preferential replication of Pichinde virus in cells with NK activity was suggested by showing that the greater numbers of infected spleen cells observed in MHA hamsters could be accounted for by a cell population that cosedimented with a peak of NK activity. Increased cellularity of thymi and spleens as well as increased cells sensitive to lymphokines was also found in MHA hamsters as compared to LSH hamsters. In the present study we found that injection of anti-asialo GM 1 serum reduced NK activity but did not alter susceptibility to virus infection. However, MHA hamsters were found to be relatively deficient in the production of interleukin 2 and injection of interleukin 2 altered the mortality of hamsters infected with Pichinde virus. These findings suggest that susceptibility to lethal infection by Pichinde virus is associated with reduced ability to produce interleukin 2 in MHA hamsters.

Animals↗
PubMed1986

Comparison of risk factors for cervical cancer in different populations.

The incidence of cervical cancer has been found to vary between populations. Risk factors of cervical cancer include early age at first marriage, multiple marriages and antibodies to herpes simplex virus type 2 (HSV-2). The interrelatedness of these risk factors was examined by comparing data collected from 428 cancer cases and 947 control women selected from 6 populations having standardized cervical cancer incidence rates varying from 9.3 to 85.1 per 100,000. Logistic regression analysis revealed that multiple marriages, early age at first marriage or pregnancy and HSV-2 antibodies were all associated with significant risk when all 3 factors were entered into the model. Cervical cancer incidence rates were best predicted by the occurrence of HSV-2 antibodies among control women. To further assess the relation between cervical cancer rates and HSV-2 antibody, 2,306 additional sera representing an 0.8% random sample of females over 9 years of age residing in the Republic of Panama were assayed for antibodies to the virus, and the occurrence of antibodies was correlated with invasive cervical cancer rates specific to each Province. Data from both the random sample and the other study populations yielded a linear relation between the occurrence of HSV-2 antibodies and the incidence of cervical cancer. An exception was found for women living in Herrera Province, Republic of Panama, who had a higher cancer rate than predicted by HSV-2 antibody occurrence. The data suggested that infection with HSV-2 is a co-variable of venereal factors, although a role for the virus in the genesis of a certain proportion of cervical cancers is not excluded.

Adult↗
PubMed1985

Case control study of cervical cancer in Herrera Province, Republic of Panama.

A previous survey found the average annual age-adjusted incidence of cervical cancer in Herrera Province, Panama, to be 79/100,000, exceeding any other reported world rate. In an effort to clarify the reasons for this excessive occurrence, a case-control study was conducted among patients diagnosed between 1974-1980. Sixty-six percent of cervical cancer patients from Herrera Province were alive and were contacted by the study team; of these 91% were successfully interviewed and provided serum specimens. The total study encompassed 156/169 surviving patients and 309 age-neighborhood matched controls. Sexual promiscuity was uncommon, but it exerted a major effect, with those reporting 4 or more life-time sex partners being at a 4-fold excess risk compared to those reporting only one partner. First intercourse at a young age was common (21% began sexual activity prior to age 16) but it failed to alter risk once number of partners was taken into account. Oral contraceptive use was associated with a 2-fold excess risk and this was not substantially affected by controlling for sexual parameters. Thirty-three percent of the study subjects had anti-herpes-simplex type-2 antibody as measured by both neutralization and radioimmunoassays. Although results of the neutralization test were not predictive of risk, women with a radioimmunoassay indicative of HSV-2 infection were at a 40% excess risk for cervical cancer after adjustment for sexual characteristics.

Adult↗
PubMed1985

Herpes simplex virus type 2 and human papillomavirus type 16 in cervicitis, dysplasia and invasive cervical carcinoma.

Sera and biopsies of cervical lesions from 55 women with benign or malignant disease were analyzed for evidence of infection with herpes simplex virus type 2 (HSV-2) or human papillomavirus (HPV). In addition, information regarding known risk factors for cervical cancer was obtained by interview. The sera were tested for HSV-2 antibodies and the biopsies were tested for HPV or HSV DNA sequences by Southern blot hybridization. HSV-2 sequences were detected in 2/13 (15%) invasive neoplasms and in 1/12 (7%) benign lesions. Under non-stringent conditions of hybridization, reactions with HPV DNA were detected in biopsies of 2/17 (12%) inflammatory lesions, 6/12 (50%) intraepithelial neoplasms and 13/20 (65%) invasive neoplasms. All but one of the positive biopsies of invasive cancer, but only 4/11 biopsies of non-invasive lesions, contained HPV-16 DNA as determined by stringent hybridization conditions. Women with cervical cancer possessed the risk factors associated with the disease. Cigarette smoking and the presence of HPV-16 DNA were the most prominent risk factors. No evidence of an interaction between HSV-2 and HPV-16 was found among the cases of invasive cervical cancer.

Adult↗
PubMed1985

Competitive inhibition by human sera of mouse monoclonal antibody binding to glycoproteins C and D of herpes simplex virus types 1 and 2.

A competitive enzyme-linked immunosorbent assay was used to test for human antibodies to antigenic sites on herpes simplex virus (HSV) glycoproteins C and D, which are recognized by mouse monoclonal antibodies. Antibodies capable of blocking the monoclonal antibodies were detected in the human sera, and the inhibition of binding correlated with the histories of herpetic infections. The binding of monoclonal antibody to glycoprotein C of HSV type 2 was inhibited primarily by sera from patients with recurrent herpes genitalis; however, the binding of the monoclonal antibodies to gC of HSV type 1 was inhibited by sera from patients previously infected with either HSV type 1 or HSV type 2. The observations suggest that the antigenic sites defined by the mouse monoclonal antibodies are recognized by the human host.

Animals↗
PubMed1985

Abrogation of anti-Pichinde virus cytotoxic T cell memory by cyclophosphamide and restoration by coinfection or interleukin 2.

Previously, we demonstrated that memory cell-mediated immune responses can be generated in Pichinde virus (PV)-primed mice after secondary challenge in vivo with homologous virus. Further, treatment of mice with cyclophosphamide (CY) before primary infection with PV abrogated the generation of H-2-restricted, virus-specific cytotoxic T lymphocytes (CTL), and rechallenge of these mice was followed by neither a primary nor a secondary CTL response. Here, we demonstrate that this CY-induced block in memory anti-PV CTL generation was not due to establishment of a persistent infection. Interestingly, this CY-induced block in memory anti-PV CTL generation was overcome by secondarily coinfecting mice with PV and lymphocytic choriomeningitis virus (LCMV) or PV and Tacaribe virus. Secondary infection with LCMV or Tacaribe virus alone did not elicit anti-PV CTL. Coinfection resulted in the generation of a PV-specific memory CTL response as judged by maximal activity on day 4 after rechallenge. Co-infection with PV and vesicular stomatitis virus, an unrelated rhabdovirus, did not efficiently restore memory anti-PV CTL responses. Memory anti-PV CTL responses were also restored when interleukin 2 (IL 2)-containing supernatants were injected i.p. after rechallenge of CY-treated mice with PV. To demonstrate that IL 2 was the responsible lymphokine in these preparations, highly purified IL 2 was added to in vitro cultures of spleen cells from CY-treated PV-primed mice. In the presence of PV-infected syngeneic macrophages, addition of purified IL 2 resulted in a dose-dependent restoration of H-2-restricted anti-PV CTL activity. The CTL precursor (CTLp) frequency of CY-treated PV-primed mice was markedly decreased from that of normal PV-primed mice. Thus, the long-lasting block in the ability to generate a PV-specific memory CTL response after CY treatment appears to be due to both a lack of helper T cell activity and a significant reduction of CTLp. However, this block may be overcome by coinfecting with viruses that cross-react at the helper T cell level or by exogenous treatment with highly purified IL 2.

Animals↗
PubMed1984

Identification and typing of herpes simplex virus by enzyme immunoassay with monoclonal antibodies.

A double-antibody enzyme immunoassay was developed for the identification and typing of herpes simplex virus (HSV) by employing a polyclonal rabbit capture antiserum together with type-common and type 2-specific monoclonal antibodies as detectors. The test successfully identified 45 type I isolates and 30 type 2 isolates as HSVs. Compared with immunofluorescent staining and restriction endonuclease analysis, enzyme immunoassay correctly typed 45 type 1 and 30 type 2 HSV isolates. Enzyme immunoassay was 100% sensitive for identification of HSV as compared with cell culture and 100% specific for typing as compared with immunofluorescence and restriction endonuclease analysis. Electron microscopy analysis suggested that approximately 10(6) virus particles were required for the identification and typing of HSV by enzyme immunoassay.

Antibodies, Monoclonal↗
PubMed1984

Localization of a type-specific antigenic site on herpes simplex virus type 2 glycoprotein D.

A herpes simplex virus type 1 strain isolated from a recurrent lesion of the nose reacted with monoclonal antibodies recognizing a type 2-specific site on glycoprotein D but not with monoclonal antibodies recognizing other type 2-specific sites. DNA sequence analysis of the glycoprotein D gene of the isolate revealed a single nucleotide alteration which changed the codon for asparagine to one encoding histidine at amino acid 97 in the protein. Histidine is located at this position in glycoprotein of herpes simplex virus type 2; thus, the monoclonal antibody 17 beta A3 recognizes an epitope located at this region of the protein.

Adult↗
PubMed1984

Reversion of mutations in the thymidine kinase gene in herpes simplex viruses resistant to phosphonoacetate.

Mutations in the DNA polymerase locus of phage, bacteria, and eukaryotic may change the mutation rates at other loci of the genome. We used resistance to phosphonoacetate to select mutants of herpes simplex virus with mutated DNA polymerase and then determined the reversion frequency of viral thymidine kinase mutation in mutants and recombinants. The results obtained indicate that mutations causing resistance to phosphonoacetate do not affect the mutation rate of the viral genes. This finding is consistent with the existence of two functional regions in the DNA polymerase molecule, one involving the pyrophosphate acceptor site and responsible for resistance to phosphonoacetate and another involved in the editing ability and recognition specificity of the enzyme.

DNA, Recombinant↗
PubMed1984

Risks associated with blood transfusion in newborn infants.

As with many other effective therapies, there are untoward side effects associated with blood transfusions in newborn infants. Discussed in this article are infectious agents transmitted by blood components, metabolic complications of transfusion, cardiac and vascular complications, hemorrhagic complications, donor erythrocyte injury, and alloimmunization to red cell and white cell antigens. Thus, potential complications must always be borne in mind when transfusing blood products.

Bacterial Infections↗
PubMed1984

Generation of memory cell-mediated immune responses after secondary infection of mice with pichinde virus.

Pichinde virus (PV), a member of the arenavirus group, was found to elicit strong cell-mediated immune responses in various strains of mice. After primary i.v. inoculation, augmentation of natural killer (NK) cell activity occurred and peaked 3 to 4 days after infection. The NK response was followed by a second peak of cytotoxic activity that was found to be H-2 restricted, virus specific, and mediated by Thy-1.2+, Lyt-2.2+ lymphocytes. This cytotoxic T lymphocyte (CTL) response peaked 7 days post infection. Neutralizing antibodies were not detectable after PV infection of the mice. In light of this, we investigated the generation and kinetics of secondary cell-mediated immune responses after reinjection of homologous virus in vivo. Slight but significant augmentation of NK activity was observed 1 day after secondary virus challenge. As in the primary response, effectors of this NK activity rapidly became sensitive to anti-Thy-1.2 and complement treatment. NK activity rapidly returned to background levels and was followed by an anamnestic CTL response that peaked 4 days after reinjection of the virus. Thus, cell-mediated immune responses appeared more rapidly after secondary challenge in vivo, and the temporal relationship between NK and CTL generation was maintained. Both secondary NK and CTL responses were generated in mice that had been pretreated with cyclophosphamide (CY), suggesting that memory cell-mediated immune responses can be reactivated in vivo without undergoing cell division. In contrast, treatment with CY before primary infection delayed the appearance of virus-induced NK activity and abrogated the generation of H-2-restricted virus-specific CTL. Rechallenge of these CY-treated NK-primed mice resulted in the rapid generation of a secondary NK response that was not followed by either a primary or secondary CTL response. The data suggest that cells mediating a nonspecific effector function may possess specific memory. We discuss our results with respect to possible NK-CTL relationships.

Animals↗
PubMed1984

Neonatal cytomegalovirus infections: the relative role of neonatal blood transfusion and maternal exposure.

A prospective study of premature infants admitted to an intensive care neonatal unit was undertaken to evaluate the relative role of blood transfusions and maternal exposure in infections caused by cytomegalovirus (CMV), varicella zoster virus (VZV) and herpes simplex virus (HSV). During the first year of life, 13.7%, 4.8% and 4% of the infants became infected with CMV, VZV and HSV, respectively, as determined by virus isolation or seroconversion. Transfusion in the newborn period did not influence the rates of VZV or HSV infections. A higher rate of CMV infections occurred in transfused (18.8%) than in non-transfused (11%) infants but the difference was not statistically significant. A significant correlation was found between maternal antibody titers and the rate of CMV infection in infants whether or not transfusion occurred. An even stronger association was found between breast feeding and CMV infections. The risk of alloimmunization to erythrocyte and leucocyte antigens was also assessed; no evidence of increased alloimmunization to these antigens was associated with transfusion.

Antibodies, Viral↗