Early cancer detection among rural and urban californians

BACKGROUND: Since the stage of cancer detection generally predicts future mortality rates, a key cancer control strategy is to increase the proportion of cancers found in the early stage. This study compared stage of detection for members of rural and urban communities to determine whether disparities were present. METHODS: The California Cancer Registry (CCR), a total population based cancer registry, was used to examine the proportion of early stage presentation for patients with breast, melanoma, and colon cancer from 1988 to 2003. Cancer stage at time of detection for these cancers was compared for rural and urban areas. RESULTS: In patients with breast cancer, there were significantly more patients presenting at early stage in 2003 compared to 1988, but no difference in the percentage of patients presenting with early stage disease between rural and urban dwellers. There were no differences in incidence in early stage cancer incidence between these groups for melanoma patients, as well. In colorectal cancer in 1988, significantly more patients presented with early stage disease in the urban areas (42% vs 34%, p < 0.02). However, over time the rural patients were diagnosed with early stage disease with the same frequency in 2003 as 1988. CONCLUSION: This analysis demonstrates that people in rural and urban areas have their breast, melanoma or colorectal cancers diagnosed at similar stages. Health care administrators may take this information into account in future strategic planning

Empowerment and Parent Gain as Mediators and Moderators of Distress in Mothers of Children with Autism Spectrum Disorders

Mothers of children with Autism Spectrum Disorders (ASD) experience considerable amounts of distress and experiences of crisis. The Family Adjustment and Adaptation Response model provides a theory for understanding the experience of distress and family crisis in families, and the purpose of the present study was to examine experiences of distress in mothers of individuals with ASD using this framework. We specifically investigated how parent empowerment and positive gain are related to their experiences of distress, whether as mediators or as moderators of child aggression. Participants included 156 mothers of children with ASD ranging in age from 4 – 21 years. Mothers completed an online survey of demographics, problem behaviors, family empowerment, positive gain, and distress. We conducted path analyses of multiple mediation and moderation. Results indicated that greater child problem behavior was related to less parent empowerment, which was related to greater maternal distress, supporting empowerment as a partial mediator. At the same time, greater child aggression was not related to maternal distress in mothers who report high rates of positive gain, suggesting that parent gain functions as a moderator. The implications for how and when clinicians intervene with families of children with ASD are discussed

Role of PCSK5 Expression in Mouse Ovarian Follicle Development: Identification of the Inhibin α- and β-Subunits as Candidate Substrates

Inhibin and activin are essential dimeric glycoproteins belonging to the transforming growth factor-beta (TGFβ) superfamily. Inhibin is a heterodimer of α- and β-subunits, whereas activin is a homodimer of β-subunits. Production of inhibin is regulated during the reproductive cycle and requires the processing of pro-ligands to produce mature hormone. Furin is a subtilisin-like proprotein convertase (proconvertase) that activates precursor proteins by cleavage at basic sites during their transit through the secretory pathway and/or at the cell surface. We hypothesized that furin-like proconvertases are central regulators of inhibin α- and β-subunit processing within the ovary. We analyzed the expression of the proconvertases furin, PCSK5, PCSK6, and PCSK7 in the developing mouse ovary by real-time quantitative RT-PCR. The data showed that proconvertase enzymes are temporally expressed in ovarian cells. With the transition from two-layer secondary to pre-antral follicle, only PCSK5 mRNA was significantly elevated. Activin A selectively enhanced expression of PCSK5 mRNA and decreased expression of furin and PCSK6 in cultured two-layer secondary follicles. Inhibition of proconvertase enzyme activity by dec-RVKR-chloromethylketone (CMK), a highly specific and potent competitive inhibitor of subtilisin-like proconvertases, significantly impeded both inhibin α- and β-subunit maturation in murine granulosa cells. Overexpression of PC5/6 in furin-deficient cells led to increased inhibin α- and βB-subunit maturation. Our data support the role of proconvertase PCSK5 in the processing of ovarian inhibin subunits during folliculogenesis and suggest that this enzyme may be an important regulator of inhibin and activin bioavailability

E-cadherin expression and bromodeoxyuridine incorporation during development of ovarian inclusion cysts in age-matched breeder and incessantly ovulated CD-1 mice

BACKGROUND: Female CD-1/Swiss Webster mice subjected to incessant ovulation for 8 months and 12-month breeder mice both developed ovarian inclusion cysts similar to serous cystadenomas. The majority of cysts appeared to be dilated rete ovarii tubules, but high ovulation number resulted in more cortical inclusion cysts. We hypothesized that comparison of inclusion cyst pathology in animals of the same age, but with differences in total lifetime ovulation number, might allow us to determine distinguishing characteristics of the two types of cyst. METHODS: Ovaries from breeder mice (BR) or females subjected to incessant ovulation (IO) were compared at 6-, 9- and 12-months of age. Ovaries were serially sectioned and cysts characterized with regard to location and histology, E-cadherin immunoreactivity and rates of BrdU incorporation. RESULTS: Inclusion cysts developed with age in BR and IO ovaries. The majority of cysts were connected to the ovarian hilus. Two cortical inclusion cysts were observed in ten IO ovaries and one in ten BR ovaries. Low or no E-cadherin immuno-staining was seen in the OSE of all mice studied. Conversely, strong membrane immuno-staining was observed in rete ovarii epithelial cells. Variable E-cadherin immunoreactivity was seen in cells of hilar inclusion cysts, with strong staining observed in cuboidal ciliated cells and little or no staining in flat epithelial cells. Two of the three cortical cysts contained papillae, which showed E-cadherin immuno-staining at the edge of cells. However hilar and cortical cysts were not distinguishable by morphology, cell type or E-cadherin immunoreactivity. BrdU incorporation in cyst cells (1.4% [95% CI: 1.0 to 2.1]) was greater than in OSE (0.7% [95% CI: 0.4 to 1.2]) and very few BrdU-labeled cells were observed in rete ovarii at any age. Incessant ovulation significantly increased BrdU incorporation in OSE of older animals. CONCLUSION: These experiments confirm ovarian inclusion cysts develop with age in the CD-1 mouse strain, irrespective of total ovulation burden. We conclude longer periods of incessant ovulation do not lead to significant changes in inclusion cyst formation or steroidogenesis in CD-1 mice and inclusion cyst type can not be distinguished by morphology, cell proliferation rate or E-cadherin immunoreactivity

Nucleoside Analogue Reverse Transcriptase Inhibitors Differentially Inhibit Human LINE-1 Retrotransposition

Intact LINE-1 elements are the only retrotransposons encoded by the human genome known to be capable of autonomous replication. Numerous cases of genetic disease have been traced to gene disruptions caused by LINE-1 retrotransposition events in germ-line cells. In addition, genomic instability resulting from LINE-1 retrotransposition in somatic cells has been proposed as a contributing factor to oncogenesis and to cancer progression. LINE-1 element activity may also play a role in normal physiology. LINE-1 retrotransposition reporter assay, we evaluated the abilities of several antiretroviral compounds to inhibit LINE-1 retrotransposition. The nucleoside analogue reverse transcriptase inhibitors (nRTIs): stavudine, zidovudine, tenofovir disoproxil fumarate, and lamivudine all inhibited LINE-1 retrotransposition with varying degrees of potencies, while the non-nucleoside HIV-1 reverse transcriptase inhibitor nevirapine showed no effect.Our data demonstrates the ability for nRTIs to suppress LINE-1 retrotransposition. This is immediately applicable to studies aimed at examining potential roles for LINE-1 retrotransposition in physiological processes. In addition, our data raises novel safety considerations for nRTIs based on their potential to disrupt physiological processes involving LINE-1 retrotransposition

Epstein-Barr Virus Evades CD4+ T Cell Responses in Lytic Cycle through BZLF1-mediated Downregulation of CD74 and the Cooperation of vBcl-2

Evasion of immune T cell responses is crucial for viruses to establish persistence in the infected host. Immune evasion mechanisms of Epstein-Barr virus (EBV) in the context of MHC-I antigen presentation have been well studied. In contrast, viral interference with MHC-II antigen presentation is less well understood, not only for EBV but also for other persistent viruses. Here we show that the EBV encoded BZLF1 can interfere with recognition by immune CD4+ effector T cells. This impaired T cell recognition occurred in the absence of a reduction in the expression of surface MHC-II, but correlated with a marked downregulation of surface CD74 on the target cells. Furthermore, impaired CD4+ T cell recognition was also observed with target cells where CD74 expression was downregulated by shRNA-mediated inhibition. BZLF1 downregulated surface CD74 via a post-transcriptional mechanism distinct from its previously reported effect on the CIITA promoter. In addition to being a chaperone for MHC-II αβ dimers, CD74 also functions as a surface receptor for macrophage Migration Inhibitory Factor and enhances cell survival through transcriptional upregulation of Bcl-2 family members. The immune-evasion function of BZLF1 therefore comes at a cost of induced toxicity. However, during EBV lytic cycle induced by BZLF1 expression, this toxicity can be overcome by expression of the vBcl-2, BHRF1, at an early stage of lytic infection. We conclude that by inhibiting apoptosis, the vBcl-2 not only maintains cell viability to allow sufficient time for synthesis and accumulation of infectious virus progeny, but also enables BZLF1 to effect its immune evasion function

Health for sale: the medicinal plant markets in Trujillo and Chiclayo, Northern Peru

Traditional methods of healing have been beneficial in many countries with or without access to conventional allopathic medicine. In the United States, these traditional practices are increasingly being sought after for illnesses that cannot be easily treated by allopathic medicine. More and more people are becoming interested in the knowledge maintained by traditional healers and in the diversity of medicinal plants that flourish in areas like Northern Peru. While scientific studies of medicinal plants are underway, concern has arisen over the preservation of both the large diversity of medicinal plants and the traditional knowledge of healing methods that accompanies them. To promote further conservation work, this study attempted to document the sources of the most popular and rarest medicinal plants sold in the markets of Trujillo (Mayorista and Hermelinda) and Chiclayo (Modelo and Moshoqueque), as well as to create an inventory of the plants sold in these markets, which will serve as a basis for comparison with future inventories. Individual markets and market stalls were subjected to cluster analysis based on the diversity of the medicinal plants they carry. The results show that markets were grouped based on the presence of: (1) common exotic medicinal plants; (2) plants used by laypeople for self-medication related to common ailments ("everyday remedies"); (3) specialized medicinal plants used by curanderos or traditional healers; and (4) highly "specialized" plants used for magical purposes. The plant trade in the study areas seems to correspond well with the specific health care demands from clientele in those areas. The specific market patterns of plant diversity observed in the present study represent a foundation for comparative market research in Peru and elsewhere

Proliferating Cell Nuclear Antigen (PCNA) Regulates Primordial Follicle Assembly by Promoting Apoptosis of Oocytes in Fetal and Neonatal Mouse Ovaries

Primordial follicles, providing all the oocytes available to a female throughout her reproductive life, assemble in perinatal ovaries with individual oocytes surrounded by granulosa cells. In mammals including the mouse, most oocytes die by apoptosis during primordial follicle assembly, but factors that regulate oocyte death remain largely unknown. Proliferating cell nuclear antigen (PCNA), a key regulator in many essential cellular processes, was shown to be differentially expressed during these processes in mouse ovaries using 2D-PAGE and MALDI-TOF/TOF methodology. A V-shaped expression pattern of PCNA in both oocytes and somatic cells was observed during the development of fetal and neonatal mouse ovaries, decreasing from 13.5 to 18.5 dpc and increasing from 18.5 dpc to 5 dpp. This was closely correlated with the meiotic prophase I progression from pre-leptotene to pachytene and from pachytene to diplotene when primordial follicles started to assemble. Inhibition of the increase of PCNA expression by RNA interference in cultured 18.5 dpc mouse ovaries strikingly reduced the apoptosis of oocytes, accompanied by down-regulation of known pro-apoptotic genes, e.g. Bax, caspase-3, and TNFα and TNFR2, and up-regulation of Bcl-2, a known anti-apoptotic gene. Moreover, reduced expression of PCNA was observed to significantly increase primordial follicle assembly, but these primordial follicles contained fewer guanulosa cells. Similar results were obtained after down-regulation by RNA interference of Ing1b, a PCNA-binding protein in the UV-induced apoptosis regulation. Thus, our results demonstrate that PCNA regulates primordial follicle assembly by promoting apoptosis of oocytes in fetal and neonatal mouse ovaries

Association of cetuximab with adverse pulmonary events in cancer patients: a comprehensive review

Compounds derived from biologic sources, or biologicals, are increasingly utilized as therapeutic agents in malignancy. Development of anti-cancer targeted therapies from biologics is increasingly being utilized. Cetuximab, a chimeric monoclonal antibody, is one such anti-cancer targeted therapeutic that has shown efficacy in quelling the rate of patient decline in colorectal, head/neck, and non-small cell lung cancer. However, due to the relatively recent addition of biologic compounds to the therapeutic arsenal, information related to adverse reactions is less well known than those seen in traditional chemotherapeutics. Dermatologic reactions have been demonstrated as the most frequent side effect cited during cetuximab therapy for malignancy; however, other effects may lead to greater morbidity. In general, pulmonary complications of therapeutics can lead to significant morbidity and mortality. The purpose of this review is to compile the various pulmonary side effects seen in patients treated with cetuximab for various malignancies, and to compare the incidence of these adverse reactions to standard therapies