Human papillomavirus infection and P53 codon 72 genotypes in a Hispanic population at high-risk for cervical cancer

Cervical cancer mortality is high in Texas, especially among Hispanic women living in south Texas and adjacent Mexico. Though human papillomavirus (HPV) infection has a causal role in the development of cervical cancer, there are no published data on the prevalence of HPV genotypes in this underscreened region. We studied 398 Hispanic women on both sides of the border along the lower Rio Grande River to determine the prevalence of HPV genotypes and risk factors for cervical cancer. Using a nested PCR system HPV was detected in 62% of cervical specimens, including all the known high-risk HPV genotypes, with HPV16 and HPV18 the most frequent (30.6% and 23.0%, respectively). Multiple infections were common (29.4% of the infected specimens), and where this occurred we were more likely to find high-risk HPV genotypes. We examined host p53 codon 72 genotype frequencies and found that patients with cervical abnormalities and women with HPV16 and HPV18 infections had a lower genotype frequency of the homozygous (AA) previously reported to be associated with cervical cancer, than uninfected women with no abnormalities. In this US/Mexico border population high rates of potentially oncogenic HPV viruses and multiple infections are consistent with observed elevated cervical cancer rates. These data are further evidence that in this underserved population HPV infections are associated with high rates of malignancy, but that host p53 genotypic variations are unlikely to be primary factors in oncogenesis.     

Mannoprotein from Cryptococcus neoformans promotes T-helper type 1 anticandidal responses in mice

We previously demonstrated that mannoprotein (MP) from Cryptococcus neoformans (CnMP) stimulates interleukin-12 production by human monocytes, thus fostering a T-helper type 1 (Th1) protective anticryptococcal response. In this paper we show that CnMP was also able to induce a Candida albicans-directed protective Th1 response. This was demonstrated for mice immunized with CnMP by induction of a delayed-type hypersensitivity (DTH) reaction to C. albicans MP (CaMP) as well as induction of gamma interferon production by CD4(+) and CD8(+) splenic T cells stimulated in vitro with CaMP. CnMP-immunized mice were also partially protected from lethal systemic challenge with C. albicans, as shown by prolonged median survival times and decreased fungal burden in the kidney. Much evidence supports the validity of these cross-reactive and functional Th1 responses: (i) a non-cross-reactive C. albicans antigen, such as enolase, did not produce a DTH response to CaMP; (ii) passive adoptive transfer of T cells primed with CnMP induced a DTH reaction; (iii) C. neoformans extract elicited a DTH response to CaMP; and (iv) a monoclonal antibody (7H6) directed against a major and immunodominant T-cell-stimulatory 65-kDa MP (MP65) of C. albicans also recognized discrete 100-kDa constituents of C. neoformans extracts, as well as secretory constituents of the fungus. These results suggest the presence of common Th1 antigenic determinants in the mannoproteic material of C. neoformans and C. albicans epitopes, which should be considered in devising common strategies for immunoprophylactic or immunotherapeutic control of the fungi.     

Effects of IFN-gamma and interleukin-1beta on major histocompatibility complex antigen and intercellular adhesion molecule-1 expression by 9L gliosarcoma: relevance to its cytolysis by alloreactive cytotoxic T lymphocytes.

To enhance the efficacy of cellular immunotherapy for gliomas, we tested the concept of using proinflammatory cytokine treatment with interferon-gamma (IFN-gamma) or interleukin-1beta (IL-1beta) or both to render glioma cells more susceptible to cytolysis by alloreactive cytotoxic T lymphocytes (aCTL). The cytokines, separately or in combination, were able to upregulate major histocompatibility complex (MHC) class I antigen or intercellular adhesion molecule-1 (ICAM-1) on Fischer rat 9L gliosarcoma cells. 9L cells were incubated in vitro for 24, 48, or 72 h with varying concentrations of rat IFN-gamma (0-2000 U/ml) or recombinant human IL-1 (rHUIL-1) (0-1000 U/ml) or both. By 48 h, IFN-gamma (500 U/ml) maximally induced the percentage of positive expressing cells and the relative antigen density of MHC class I and ICAM-1 on 9L cells, whereas IL-1 induced only ICAM-1 expression. Simultaneous incubation of IL-1 with IFN-gamma did not further affect the induction of class I on 9L cells more than that achieved with IFN-gamma alone. 9L cells with upregulated MHC class I and ICAM-1 expression were more sensitive to lysis by aCTL in in vitro cytotoxicity assays, regardless of whether the precursor aCTL came from naive or from 9L-immunized rats. Furthermore, inhibition of 9L cytotoxicity in assays that included blocking antibodies to MHC class I or to ICAM-1 revealed that T cell receptor (TCR) interactions with MHC class I and that ICAM-1 interactions with lymphocyte function-associated-1 (LFA-1) antigen account for a portion of the glioma lysis by aCTL.     

Clarification of the Innervation of the Bladder,External Urethral Sphincter and Clitoris: A Neuronal Tracing Study in Female Mongrel Hound Dogs

Many studies examining the innervation of genitourinary structures focus on either afferent or efferent inputs, or on only one structure of the system. We aimed to clarify innervation of the bladder, external urethral sphincter (EUS) and clitoris. Retrograde dyes were injected into each end organ in female dogs. Spinal cord, mid‐bladder, and spinal, caudal mesenteric, sympathetic trunk and pelvic plexus ganglia were examined for retrograde dye‐labeled neurons. Neurons retrogradely labeled from the bladder were found primarily in L7‐S2 spinal ganglia, spinal cord lateral zona intermedia at S1‐S3 levels, caudal mesenteric ganglia, T11‐L2 and L6‐S2 sympathetic trunk ganglia, and pelvic plexus ganglia. The mid‐bladder wall contained many intramural ganglia neurons labeled anterogradely from the pelvic nerve, and intramural ganglia retrogradely labeled from dye labeling sites surrounding ureteral orifices. Neurons retrogradely labeled from the clitoris were found only in L7 and S1 spinal ganglia, L7‐S3 spinal cord lateral zona intermedia, and S1 sympathetic trunk ganglia, and caudal mesenteric ganglia. Neurons retrogradely labeled from the EUS were found in primarily at S1 and S2 spinal ganglia, spinal cord lamina IX at S1‐S3, caudal mesenteric ganglia, and S1‐S2 sympathetic trunk ganglia. Thus, direct inputs from the spinal cord to each end organ were identified, as well as multisynaptic circuits involving several ganglia, including intramural ganglia in the bladder wall. Knowledge of this complex circuitry of afferent and efferent inputs to genitourinary structures is necessary to understand and treat genitourinary dysfunction. Anat Rec, 2018. © 2018 Wiley Periodicals, Inc.     

No association between positive intraoperative allograft cultures and infection rates after reconstructive knee ligament surgery

Background

Several reports of severe infections associated with allograft tissue in knee reconstructive surgery have led many surgeons to consider routine intraoperative culture of allograft tissue before implantation. Thus, the purpose of this study was to determine the prevalence of positive soft tissue allograft cultures in reconstructive knee surgery, and evaluate its association with surgical site infection.

Social environment alters central distribution of estrogen receptor alpha in juvenile prairie voles

It is well established that social environment, particularly isolation, has a significant impact on social behaviors and neuroendocrine responses. Estrogen receptor alpha (ERα) expression in limbic structures and associated nuclei is related to the display of social behaviors. We hypothesized that the stress of isolation would cause changes in the pattern of ERα expression in the brain. Using a highly social (typically monogamous and biparental) rodent species, the prairie vole (Microtus ochrogaster), we housed juvenile voles with a sibling, stranger or in isolation for either 4 days or 21 days. Housing manipulations began following weaning from parents and group housed siblings. Rodents may be especially sensitive to manipulations of their social environment during this juvenile period. In particular, female prairie voles are induced ovulators, reliant upon exposure to an unrelated male (male urine) to become reproductively active. ERα immunoreactivity was quantified in the medial preoptic area (MPOA), bed nucleus of the stria terminalis (BST), ventromedial nucleus of the hypothalamus (VMH) and medial amygdala (MeA). Significantly fewer ERα immunoreactive (ERα-ir) cells were labeled in the MPOA and BST of females isolated for 21 days compared with stranger housed females. Non-significant differences were shown in the VMH and MeA of females. No differences were found in voles isolated for 4 days. These results suggest that female prairie voles may be more sensitive than males to manipulations of their social environment during the juvenile period.     

PRIME: impact of previous mental health problems on health-related quality of life in women with childbirth trauma

We investigated the impact of pre-existing mental ill health on postpartum maternal outcomes. Women reporting childbirth trauma received counselling (Promoting Resilience in Mothers' Emotions; n?=?137) or parenting support (n?=?125) at birth and 6 weeks. The EuroQol Five dimensional (EQ-5D)-measured health-related quality of life at 6 weeks, 6 and 12 months. At 12 months, EQ-5D was better for women without mental health problems receiving PRIME (mean difference (MD) 0.06; 95 % confidence interval (CI) 0.02 to 0.10) or parenting support (MD 0.08; 95 % CI 0.01 to 0.14). Pre-existing mental health conditions influence quality of life in women with childbirth trauma.