1,721,005 research outputs found
Molecular biology of papillomaviruses in pre-malignant cervical infection
No full textThe samples analysed were cervical scrapes taken at a colposcopy clinic. HPVs were detected in 90% of specimens with low grade lesions (CIN 1) and 100% of high grade lesions (CIN3). HPV types commonly found in cancer (high risk types 16, 18, 31, and 45) were detected in 80% of specimens with CIN 3, but only 40% of specimens with CIN 1). Moderate risk HPV types (including types 33, 35, 39, and 56) were detected in 19% of CIN 3 and 34% of CIN 1 and low risk HPV types (e.g. 6, 11, 42, and 66) were detected in 11% of CIN 1, but less than 1% of samples with CIN 3. No positive predictive value was found using viral load as an indicator of disease severity. Cervical infection with herpesviruses was found more often in women with progressing CIN, but there was no correlation with cervical cytokine or chemokine production and grade of CIN. However, mixed HPV infections increased in incidence with increasing lesion severity.The most commonly isolated HPV type in all grades of CIN was HPV-16. Transcripts coding for the oncogenic proteins, E6 and E7, were more commonly detected in high grade lesion severity.The production of transcripts for host proteins implicated in uncontrolled cellular replication was investigated. Survivin transcripts were present in 30% of CIN samples. Interestingly, samples not expressing survivin transcripts contained higher levels of HPV-16 E6 transcripts. A polymorphism in intron 6 of the p53 gene was linked to the presence of CIN. However, this polymorphism only accounted for susceptibility to CIN in a minor group of women.</p
The influence of a high fat diet on bone and soft tissue formation in Matrix Gla Protein knockout mice
No full textStudies suggest bone growth and development are influenced by maternal nutrition, during intrauterine and early postnatal life. This study assessed the role of MGP and a maternal high fat diet on vitamin K-dependent proteins’ gene expression and their impact on bone formation. Knockout (KO) offspring were smaller than wild type (WT) littermates, yet possessed the same volume of intrascapular brown adipose tissue. The total proportion of body fat was reduced, but only in animals on a control diet. Lung air volume was observed to be comparable in both KO and WT animals on the same diet. The degree of aortic calcification was reduced in KO animals maintained on a HF diet. KO females on the high fat diet showed reduced cortical bone volume and thickness in the femur and tibia. Gene expression levels of GGCX and VKOR were reduced in control fed KO animals suggesting a potential link between gene expression levels of MGP, GGCX, and VKOR and total volumes of bone, calcified soft tissue, and iBAT; with implications for modulation of body length and mass. Our results confirm the important role for vitamin K in bone and calcified soft tissue, but now extend this role to include iBAT
Pancreas deficiency modifies bone development in the ovine fetus near term.
Full text linkHormones have an important role in the regulation of fetal growth and development, especially in response to nutrient availability in utero. Using micro-CT and an electromagnetic three-point bend test, this study examined the effect of pancreas removal at 0.8 fraction of gestation on the developing bone structure and mechanical strength in fetal sheep. When fetuses were studied at 10 and 25 days after surgery, pancreatectomy caused hypoinsulinaemia, hyperglycaemia and growth retardation which was associated with low plasma concentrations of leptin and a marker of osteoclast activity and collagen degradation. In pancreatectomized fetuses compared to control fetuses, limb lengths were shorter, and trabecular (Tb) bone in the metatarsi showed greater bone volume fraction, Tb thickness, degree of anisotropy and porosity, and lower fractional bone surface area and Tb spacing. Mechanical strength testing showed that pancreas deficiency was associated with increased stiffness and a greater maximal weight load at fracture in a subset of fetuses studied near term. Overall, pancreas deficiency in utero slowed the growth of the fetal skeleton and adapted the developing bone to generate a more compact and connected structure. Maintenance of bone strength in growth-retarded limbs is especially important in a precocial species in preparation for skeletal loading and locomotion at birth
Pilot study to assess the presence of Chlamydia trachomatis in urine from 18-30-year-old males using EIA/IF and PCR
No full textContext. To increase detection, urine samples from young males could be opportunistically tested for Chlamydia trachomatis.Objective. To determine C. trachomatis prevalence in urine, optimum specimen and compare sensitivity/feasibility of routine use of different testing methods.Design. Group A, ‘sterile’ pyuria samples June 1998–January 1999, tested by enzyme immunoassay (EIA) and, if reactive, by immunofluorescence (IF). Subsequently batch-tested by polymerase chain reaction (PCR). Group B, consecutive urine samples October 1998–January 1999; batch-tested by PCR.Setting. Microbiology laboratory.Samples. From males aged 18–30 years; group A = 71, group B = 83.Main outcome measures. Chlamydia trachomatis positive if EIA- and IF- or PCR-positive.Results. Group A: 12 EIA/IF-positive; 9/12 and 15 EIAnegative samples PCR-positive. Group B: 11 PCR-positive; 8/11 showed ‘sterile’pyuria.Conclusions.Opportunistic testing of urine from young men shows a significant number of C. trachomatis infections. ‘Sterile’ pyuria samples are optimal. EIA/IF are less sensitive than PCR but can be routinely performed and detect a significant proportion of cases.<br/
Biological and clinical insight from analysis of the tumor B-cell 2 receptor structure and function in chronic lymphocytic Leukemia
No full textThe B-cell receptor (BCR) is essential to the behavior of the majority of normal and neoplastic mature B cells. The identification in 1999 of the two major CLL subsets expressing unmutated immunoglobulin (Ig) variable region genes (U-IGHV, U-CLL) of pre-germinal center origin and poor prognosis, and mutated IGHV (M-CLL) of post-germinal center origin and good prognosis, ignited intensive investigations on structure and function of the tumor BCR. These investigations have provided fundamental insight into CLL biology and eventually the mechanistic rationale for the development of successful therapies targeting BCR signaling. U-CLL and M-CLL are characterized by variable low surface IgM (sIgM) expression and signaling capacity. Variability of sIgM can in part be explained by chronic engagement with (auto)antigen at tissue sites. However, other environmental elements, genetic changes, and epigenetic signatures also contribute to the sIgM variability. The variable levels have consequences on the behavior of CLL, which is in a state of anergy with an indolent clinical course when sIgM expression is low, or pushed towards proliferation and a more aggressive clinical course when sIgM expression is high. Efficacy of therapies that target BTK may also be affected by the variable sIgM levels and signaling and, in part, explain the development of resistance
Maternal obesity during pregnancy and lactation influences offspring obesogenic adipogenesis but not developmental adipogenesis in mice
Full text linkObesity is an escalating health crisis of pandemic proportions and by all accounts it has yet to reach its peak. Growing evidence suggests that obesity may have its origins in utero. Recent studies have shown that maternal obesity during pregnancy may promote adipogenesis in offspring. However, these studies were largely based on cell culture models. Whether or not maternal obesity impacts on offspring adipogenesis in vivo remains to be fully established. Furthermore, in vivo adipogenic differentiation has been shown to happen at distinct time periods, one during development (developmental adipogenesis—which is complete by 4 weeks of age in mice) and another in adulthood in response to feeding a high-fat (HF) diet (obesogenic adipogenesis). We therefore set out to determine whether maternal obesity impacted on offspring adipocyte hyperplasia in vivo and whether maternal obesity impacted on developmental or obesogenic adipogenesis, or both. Our findings reveal that maternal obesity is associated with enhanced obesogenic adipogenesis in HF-fed offspring. Interestingly, in newly weaned (4-week-old) offspring, maternal obesity is associated with adipocyte hypertrophy, but there were no changes in adipocyte number. Our results suggest that maternal obesity impacts on offspring obesogenic adipogenesis but does not affect developmental adipogenesis
BMP-2 localisation in nanoclay decorated hyaluronic acid hydrogels enhances osteoinduction
No full textSynchronous ovarian and cervical squamous intraepithelial neoplasia: an analysis of HPV status
No full textIn contrast to the strong association between human papillomavirus (HPV) and cervical intraepithelial neoplasia (CIN), the relationship between HPV and squamous epithelial lesions of the ovary is less clear. We report a case of synchronous ovarian and cervical squamous intraepithelial neoplasia. To investigate the possible association between HPV and squamous intraepithelial neoplasia/carcinomain situ(CIS) of the ovary, DNA was extracted from paraffin-embedded tissues including normal cervix, CIN, CIS from both ovaries, and an area of ovarian endometriosis. All samples were positive for HPV 16 E6 except for one of the two samples from the normal cervical squamous epithelium. These results support the hypothesis that HPV may be involved in the development of ovarian squamous intraepithelial neoplasi
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