Polarity of prostate specific membrane antigen,prostate stem cell antigen,and prostate specific antigen in prostate tissue and in a cultured epithelial cell line

BACKGROUND: Madin-Darby canine kidney (MDCK) cells are immortalized epithelial cells that have been used extensively as a model system to study intracellular molecular trafficking, polarized expression, and secretion of proteins in various epithelia. In order to determine if MDCK cells might serve as a model to study molecular events within prostate epithelial cells, we have evaluated the polarized distribution of three prostate restricted proteins, PSMA, PSCA, and PSA, in situ, and in MDCK cells. METHODS: Using immunofluorescence, confocal microscopy, cell surface biotinylation, antibody internalization, and biochemical assays we evaluated surface expression and secretion of three prostate restricted proteins expressed in MDCK cells. We compared these patterns of expression to results observed within prostatic epithelium. RESULTS: We demonstrate that PSMA is localized primarily to the apical plasma membrane in both the prostatic epithelium and transfected MDCK cells, whereas PSCA is expressed in a non-polarized fashion. We also show that PSA is secreted predominantly from the apical surface of transfected MDCK cells, consistent with in vivo observations. CONCLUSIONS: Similar patterns of localization among MDCK and prostatic epithelial cells suggest that the mechanisms of polarized sorting within these cell types are conserved. Thus, MDCK cells offer a useful model system to study mechanisms of targeting of these proteins within the prostate.     

Pregnancy-associated breast cancer: spectrum of imaging appearances

Delay in diagnosis of pregnancy-associated breast cancer (PABC) is common, often attributed to the difficulty in evaluating tumours in the gravid breast, low awareness among physicians and reluctance of patients and physicians to perform imaging or invasive procedures during pregnancy. Familiarity with imaging features of PABC is crucial for prompt diagnosis. This article illustrates imaging findings of PABC and provides an approach for the evaluation of pregnant and lactating women with palpable abnormalities.Pregnancy-associated breast cancer (PABC) is defined as cancer diagnosed during pregnancy or in the first 12 months post partum, or at any time while the patient is lactating [1]. PABC is a rare but serious occurrence with an incidence of approximately 0.3/1000 pregnancies [2]. As more and more women choose to delay childbearing until their 30s or 40s, there may be an increase in the incidence of PABC, as the proportion of pregnant women at an advanced age who are already at a higher risk of breast carcinoma increases. Around two-thirds of all PABC cases are diagnosed in the post-partum period, mostly in the first six months following delivery.The diagnosis of PABC is often delayed and remains challenging because of underlying hormone-induced anatomical and physiological changes occurring in breast tissue. The lack of awareness of PABC may preclude timely imaging or biopsy, leading to larger and more advanced neoplasms at diagnosis compared with age-matched non-PABC cases [3].The aim of this pictorial review is to increase awareness of PABC by illustrating its imaging spectrum. This article also emphasises the importance of mammographic and sonographic evaluation of pregnant and lactating women with palpable abnormalities.     

Iatrogenic secondary post-partum haemorrhage: apropos of two uncommon cases

In this article we would like to highlight uterine pseudoaneurysm as a cause of secondary post-partum haemorrhage following Caesarean section. We would like to stress Doppler ultrasound scan as the initial screening modality for this condition. We also describe angioembolization as the prudent treatment option for this condition rather than resorting to surgery.     

Gestational impaired glucose tolerance (GIGT)-induced suppression of fetal thyroid secretion: effect on fetal outcome

Introduction: Gestational impaired glucose tolerance (GIGT) is a milder form of gestational diabetes mellitus (GDM), which is often poorly managed. Although, GDM is known to be associated with increased incidence of thyroid dysfunction, no study has been done to study the effect of GIGT on thyroid status and its effect on fetal outcome. Here, we carried out a study to assess thyroid function and glycemic status in both maternal and cord blood of the subjects with GIGT, and to find their association with the fetal outcome.

Materials and methods: Women who came to the hospital for safe confinement during 37–40th weeks of gestation were recruited in the study. Based on the 2?hours post prandial blood glucose levels with 75 grams OGTT, done at 24–28 weeks of gestation, all the subjects were stratified into two groups: (1) Cases or GIGT group – women with blood glucose levels between 120 and 140?mg/dl and (2) Controls – women with blood glucose levels of less than 120?mg/dl. Three milliliters of venous blood was collected from mothers and 3?ml of cord blood was collected during delivery. New-borns were assessed for birth weight, head circumference, abdominal circumference, thigh circumference, and crown-heel length. Glycated hemoglobin was carried out using immunoturbidimetry (DiaSys Diagnostic Systems GmbH, Holzheim, Germany) and fructosamine was estimated using dye binding method (Biosystems, Spain). Estimation of total T₃ (TT3), free T₃ (FT₃), total T₄ (TT₄), free T₄ (FT₄), and TSH was done by chemiluminescence in Siemens Advia Centaur CP using competitive immunoassay.

Results: Although within the normal reference range, GIGT mothers had higher concentration of free and total T₄ than controls. Cord fructosamine levels were significantly higher in babies of GIGT mothers than controls, indicating the reflection of maternal hyperglycemia. There was a positive correlation between the maternal glycated hemoglobin and cord blood fructosamine in the GIGT group. Statistically significant lower levels of total T₃ and T₄ with high TSH levels were found in babies with GIGT mothers, indicating the suppressive effect of maternal hyperglycemia on fetal thyroid function. Birth weight, head circumference, and thigh circumference were significantly higher in babies born to mothers with GIGT, which may be a combined effect of maternal hyperglycemia and fetal thyroid suppression.

Conclusions: Maternal hyperglycemia, even in milder form of GIGT may cause suppression of fetal thyroid function. Both these factors may predispose to change in fetal anthropometry, leading to a large baby. Therefore, it is recommended to evaluate maternal and cord thyroid function for timely management strategies.     

Dysfunction of ouabain-induced cardiac contractility in mice with heart-specific ablation of Na,K-ATPase β1-subunit

Na,K-ATPase is composed of two essential α- and β-subunits, both of which have multiple isoforms. Evidence indicates that the Na,K-ATPase enzymatic activity as well as its α₁, α₃ and β₁ isoforms are reduced in the failing human heart. The catalytic α-subunit is the receptor for cardiac glycosides such as digitalis, used for the treatment of congestive heart failure. The role of the Na,K-ATPase β₁-subunit (Na,K-β₁) in cardiac function is not known. We used Cre/loxP technology to inactivate the Na,K-β₁ gene exclusively in the ventricular cardiomyocytes. Animals with homozygous Na,K-β₁ gene excision were born at the expected Mendelian ratio, grew into adulthood, and appeared to be healthy until 10 months of age. At 13–14 months, these mice had 13% higher heart/body weight ratios, and reduced contractility as revealed by echocardiography compared to their wild-type (WT) littermates. Pressure overload by transverse aortic constriction (TAC) in younger mice, resulted in compensated hypertrophy in WT mice, but decompensation in the Na,K-β₁ KO mice. The young KO survivors of TAC exhibited decreased contractile function and mimicked the effects of the Na,K-β₁ KO in older mice. Further, we show that intact hearts of Na,K-β₁ KO anesthetized mice as well as isolated cardiomyocytes were insensitive to ouabain-induced positive inotropy. This insensitivity was associated with a reduction in NCX1, one of the proteins involved in regulating cardiac contractility. In conclusion, our results demonstrate that Na,K-β₁ plays an essential role in regulating cardiac contractility and that its loss is associated with significant pathophysiology of the heart.     

Kidney Disease among Patients with Sickle Cell Disease,Hemoglobin SS and SC

Background and objectives

Sickle cell disease (SCD) is an inherited anemia that afflicts millions worldwide. Kidney disease is a major contributor to its morbidity and mortality. We examined contemporary and historical SCD populations to understand how renal disease behaved in hemoglobin SS (HbSS) compared with HbSC.

Design, setting, participants, & measurements

Kidney function was examined in the multicentered Treatment of Pulmonary Hypertension and Sickle Cell Disease with Sildenafil Therapy (Walk-PHaSST) Trial (HbSS=463; HbSC=127; years 2007–2009) and historical comparator populations from the Cooperative Study of Sickle Cell Disease (CSSCD; HbSS=708) and the Multicenter Study of Hydroxyurea in Sickle Cell Disease (MSH; HbSS=299).

Results

In adults with SCD, eGFR was lower among older individuals: −1.78 ml/min per 1.73 m² per year of age (95% confidence interval [95% CI], −2.06 to −1.50; Walk-PHaSST Trial), −1.75 ml/min per 1.73 m² per year of age (95% CI, −2.05 to −1.44; MSH), and −1.69 ml/min per 1.73 m² per year of age (95% CI, −2.00 to −1.38; CSSCD) in HbSS compared with −1.09 ml/min per 1.73 m² per year of age (95% CI, −1.39 to −0.75) in HbSC (Walk-PHaSST Trial). Macroalbuminuria was seen in 20% of participants with SCD (HbSS or HbSC; P=0.45; Walk-PHaSST Trial), but microalbuminuria was more prevalent in HbSS (44% versus 23% in HbSC; P<0.002). In the Walk-PHaSST Trial, albuminuria was associated with hemolysis (higher lactate dehydrogenase, P<0.001; higher absolute reticulocyte count, P<0.02; and lower Hb, P=0.07) and elevated systolic BP (P<0.001) in HbSS. One half of all participants with HbSS (20 of 39) versus one fifth without (41 of 228) elevated tricuspid regurgitant jet velocity (≥3 m/s; adverse prognostic indicator in SCD) had macroalbuminuria (P<0.001). In the CSSCD, overt proteinuria, detected (less sensitively) by urine dipstick, associated with higher 3-year mortality (odds ratio, 2.48; 95% CI, 1.07 to 5.77). Serum bicarbonate was lower in HbSS (23.8 versus 24.8 mEq/dl in HbSC; P<0.05) and associated with reticulocytopenic anemia and decreased renal function.

Conclusions

In SCD, albuminuria or proteinuria was highly prevalent, in HbSS more than in HbSC. Proteinuria associated with mortality in HbSS. Older individuals had a lower than expected eGFR, and this was more prominent in HbSS. Current management does not routinely address renal complications in SCD, which could plausibly reduce morbidity and mortality.     

Cytotoxic Effect of Silver Nanoparticles Synthesized from Sargassum wightii on Cervical Cancer Cell Line

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - The biological synthesis of the metallic nanoparticle is gaining more interest, as it is more reliable and...     

Aggressive lymphoma subtype is a risk factor for venous thrombosis. Development of lymphoma - specific venous thrombosis prediction models

Venous thromboembolic events (VTE) are a frequent complication of lymphoma. We conducted a retrospective analysis to compare VTE risk in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). Subjects were randomly assigned to training and validation sets to identify risk factors of VTE and evaluate risk model performance, including the Khorana score. A group of 790 patients were diagnosed from 2002 to 2014 (DLBCL = 542, FL = 248). Median follow- up was 49 months. We observed 106 VTE, with higher incidence in DLBCL (5-year cumulative incidence = 16.3% vs 3.8% in FL patients). Five-year OS for patients with VTE was 51.4% vs 73.1% in patients without VTE (P < .001). Baseline VTE risk factors identified in the training cohort included lymphoma subtype, previous VTE, ECOG performance status ≥2, decreased albumin, increased calcium, elevated WBC, absolute lymphocyte count or monocyte count, and presence of bulky disease. Addition of new variables to the Khorana score improved its performance measured by Akaike information criterion and Concordance index. A new risk model including lymphoma subtype, albumin, WBC count, and bulky disease was validated in time-based ROC analyses. These findings were confirmed in the validation cohort. Lymphoma subtypes have different VTE risk. The effect of lymphoma subtype was independent from disease burden and the use of systemic therapy. The Khorana risk-score was validated in time to event analyses, and a more robust lymphoma-specific VTE risk score is proposed. These findings suggest lymphoma patients with highest VTE risk can be identified with baseline parameters.     

Radiological assessment of mesenteric and retroperitoneal cysts in adults: is there a role for chemical shift MRI?

Objective

The purpose of this study was to assess the potential role for chemical shift magnetic resonance imaging (MRI) in identifying lymphangiomas from other cystic mesenteric and retroperitoneal masses.

Materials and methods

A retrospective search of radiology database identified 24 consecutive patients with mesenteric and retroperitoneal cysts (nine men, 15 women; mean age, 41 years; age range, 19-75 years) who had undergone MR which included in-phase and opposed-phase chemical shift imaging. Signal intensity (SI) decrease between in-phase and opposed-phase MR images of the cyst was evaluated qualitatively by two radiologists. Ultrasound (US), computed tomography (CT), and MRI findings of the morphological appearances of all the cystic lesions that demonstrated significant signal drop on chemical shift MR were also recorded.

Results

Of mesenteric and retroperitoneal cysts, 33% (8/24) revealed qualitative decrease in intensity on opposed-phase MR images relative to that seen on in-phase images. On ultrasound, these cysts demonstrated anechoic simple fluid. Their mean CT attenuation was 13 HU (range: 5-20 HU). Signal loss on fat-suppressed T1-weighted sequences was displayed only by a single cyst. None of the lesions with qualitative SI decrease on opposed-phase MR showed suggestion of lipid on US and CT.

Conclusion

The presence of intra cystic lipid detected by chemical shift MR may not be overt on cross-sectional imaging such as US and CT. Chemical shift MRI provides additional sensitivity and specificity as an imaging test for demonstration of lipid within mesenteric and retroperitoneal cysts enabling a higher diagnostic yield for lymphangioma leading to more appropriate patient management.