Quantitative assessment of Tn antigen in breast tissue micro-arrays using CdSe aqueous quantum dots

In this study, we examined the use of CdSe aqueous quantum dots (AQDs) each conjugated to three streptavidin as a fluorescent label to image Tn antigen expression in various breast tissues via a sandwich staining procedure where the primary monoclonal anti-Tn antibody was bound to the Tn antigen on the tissue, a biotin-labeled secondary antibody was bound to the primary anti-Tn antibody, and finally the streptavidin-conjugated AQDs were bound to the biotin on the secondary antibody. We evaluated the AQD staining of Tn antigen on tissue microarrays consisting of 395 cores from 115 cases including three tumor cores and one normal-tissue core from each breast cancer case and three tumor cores from each benign case. The results indicated AQD-Tn staining was positive in more than 90% of the cells in the cancer cores but not the cells in the normal-tissue cores and the benign tumor cores. As a result, AQD-Tn staining exhibited 95% sensitivity and 90% specificity in differentiating breast cancer against normal breast tissues and benign breast conditions. These results were better than the 90% sensitivity and 80% specificity exhibited by the corresponding horse radish peroxidase (HRP) staining using the same antibodies on the same tissues and those of previous studies that used different fluorescent labels to image Tn antigen. In addition to sensitivity and specificity, the current AQD-Tn staining with a definitive threshold was quantitative.     

Trauma‐induced dentigerous cyst involving an inverted impacted mesiodens: case report

Abstract – There have been only a small number of studies on the association of dentigerous cysts with supernumerary teeth. The purpose of this article was to report the case of a dentigerous cyst associated with an impacted inverted mesiodens that developed secondary to trauma to its predecessor, a non‐vital permanent maxillary central incisor. As a consequence of trauma, the central incisor’s root development was prematurely arrested and the open apex lay close to the follicle of the underlying inverted mesiodens. The negligent attitude of both the child and parent in seeking dental treatment was a contributing factor. The case was further complicated by impaction of the adjacent permanent central incisor due to the presence of another unerupted but normally oriented mesiodens. Occlusal and Intraoral periapical radiographs revealed a well‐defined radiolucent area surrounding the inverted mesiodens. Microscopic examination revealed a cystic cavity that was lined by 2–3 cell thick non‐keratinized stratified squamous epithelium resembling reduced enamel epithelium. Dentigerous cysts associated with impacted permanent teeth are not uncommon but the cysts which are induced by trauma are uncommon. Development of trauma‐induced dentigerous cyst around an inverted impacted mesiodens associated with the periapical area of a traumatized, non‐vital, immature permanent central incisor is a rare occurrence.     

Painful vertical diplopia as a presentation of a pituitary mass

Background  

Pituitary tumours may present with a variety of neurological and endocrinological signs and symptoms. It is very rare however for them to present with sudden onset painful diplopia. The current literature and possible mechanisms for this are discussed.     

Sexual Activity in Older Adults with Visual Impairment: Findings from the English Longitudinal Study of Ageing

Sexuality and Disability - Sexual activity is a central component of intimate relationships and has been shown to have numerous benefits for health and wellbeing. Studies have shown that people...     

Effects of chronic ethanol drinking on the blood brain barrier and ensuing neuronal toxicity in alcohol-preferring rats subjected to intraperitoneal LPS injection

Aims: Although alcohol drinking impairs the blood–brainbarrier (BBB), the underlying mechanism is not fully understood.Thus, the effects of chronic ethanol drinking on the BBB werestudied in vivo. Methods: Alcohol-preferring rats were givenfor 70 days free choice water and 15% ethanol. Then, they receivedLPS by i.p. injection. Efflux of [¹⁴C]sucrose or [¹⁴C]dextranwas measured by their microinjection into the brain. Endothelialcells and neurons were isolated from the brain and analysedfor mitogen-activated protein kinase (MAPK) and the tight-junction(TJ) protein phosphorylation, NFB activation, mRNA levels ofTJ proteins, inducible nitric oxide synthase, tumour necrosisfactor , interleukin-1 ß (IL-1ß), IL-10,CASPASE-8, and DNA damage. Results: LPS transiently increased[¹⁴C]sucrose efflux in water drinking, while it caused a lastingincrease in [¹⁴C]sucrose and [¹⁴C]dextran efflux in ethanol-drinkingrats. The time-course of changes in the TJ correlated with (i)an increase in extracellular signal-regulated kinase (ERK),p38^mapk Jun-N-terminal Kinase (JNK), and TJ protein phosphorylation,(ii) RelA-p50 and p50-p50 activation, and (iii) a decrease inthe TJ proteins' mRNA levels in endothelial cells and neurons.Apoptotic cells were detected in water drinking and LPS (WC-LPS)neurons at 24 h after LPS exposure. Neurons from Et-LPS ratsdid not exhibit apoptosis. Conclusions: LPS injection in WC-LPSrats transiently disrupted the BBB. Lack of JNK activation andCASPASE-8 may be responsible for lack of apoptosis in endothelialcells and vice versa in neurons. Chronic alcohol drinking inethanol drinking and LPS (Et-LPS) rats augmented and dysregulatedthe LPS-induced BBB abnormalities but suppressed apoptosis inneurons.     

Carotid plaque spaces relate to symptoms and ultrasound scattering

We have previously found that spectral analysis of ultrasound (US) can discriminate in vitro plaques from asymptomatic and symptomatic (transient ischemic attack within previous 4 weeks) patients. That study found no differences in percentages of lipid or thrombus between the two groups by optical microscopy/planimetry. The present study was to find out if another feature from the microscopy could show a difference. The number and size of spaces resulting from cell death or new blood vessels were measured to see if they related to symptoms or could help explain US differentiation. Twelve plaques from each group were examined by optical microscopy. The sizes and concentrations of two kinds of spaces, endothelial lined (vessel spaces) and unlined (tissue spaces), were correlated both with symptoms and also with the US tissue characterization scores from the previous study. Symptomatic vs. asymptomatic plaques showed a higher concentration and a larger size: 0.87 vs. 0.21 per mm(2) (p < 0.005) and 154 vs. 110 microm (p < 0.02). A discriminant function of spaces with symptoms as dependent variables correctly identified 91.7% of the plaques (p < 0.001). The concentration in plaques previously designated by US as true positive plaques or true negative was 1.21 vs. 0.22 per mm(2) (p < 0.005). spaces were increased in plaques of symptomatic patients and were related to UTC scores. Both the lined and unlined spaces were useful as predictors.     

Genistein potentiates the growth inhibitory effects of 1,25-dihydroxyvitamin D3 in DU145 human prostate cancer cells: role of the direct inhibition of CYP24 enzyme activity

In a search for improved therapies for prostate cancer, we investigated the effect of genistein in combination with 1alpha-25-dihydroxyvitamin D3 [1,25(OH)2D3], on the growth of DU145 human prostate cancer cells. DU145 cells were very resistant to the growth inhibitory action of 1,25(OH)2D3 or genistein when administered individually. However, the combination caused a significant growth inhibition seen at lower concentrations of both agents. 1,25(OH)2D3 induces the expression of the CYP24 gene, which codes for the enzyme that initiates the catabolism of 1,25(OH)2D3. We showed for the first time that genistein at low doses (50-100 nM) directly inhibited CYP24 at the enzyme level. Addition of genistein to mitochondrial preparations inhibited CYP24 enzyme activity in a noncompetitive manner. CYP24 inhibition by genistein increased the half-life of 1,25(OH)2D3 thereby augmenting the homologous up-regulation of the vitamin D receptor (VDR) both at the mRNA and protein levels. Genistein co-treatment enhanced 1,25(OH)2D3-mediated transactivation of the vitamin D responsive reporters OC-Luc and OP-Luc transfected into DU145 cells. Consistent with the growth inhibition due to the combination treatment, significant changes in the expression of genes involved in growth arrest and apoptosis were seen. We conclude that genistein potentiates the antiproliferative actions of 1,25(OH)2D3 in DU145 cells by two mechanisms: (i) an increase in the half-life of 1,25(OH)2D3 due to the direct inhibition of CYP24 enzyme activity and (ii) an amplification of the homologous up-regulation of VDR. Together these two effects lead to a substantial enhancement of the cellular responses to the growth inhibitory and pro-apoptotic signaling by 1,25(OH)2D3.     

Case of fulminant leptospirosis in a renal transplant patient

Abstract: We present a case of fulminant leptospirosis that was acquired in the suburban area by a 48-year-old male renal transplant recipient. He developed acute renal and hepatic failure with profound jaundice. Spirochetes were identified on liver biopsy. Weil's disease was suspected, and the diagnosis was further supported by a positive serum Leptospira interrogans icterohaemorrhagiae antibody titer. Unfortunately, he suffered from recurrent lower gastrointestinal bleeding, had a prolonged hospital course, and eventually succumbed to overwhelming sepsis. This case is the third report to our knowledge of leptospirosis in a renal transplant recipient in the English literature.