Transcriptional repression of IFNß1 by ATF2 confers melanoma resistance to therapy.

The resistance of melanoma to current treatment modalities represents a major obstacle for durable therapeutic response, and thus the elucidation of mechanisms of resistance is urgently needed. The crucial functions of activating transcription factor-2 (ATF2) in the development and therapeutic resistance of melanoma have been previously reported, although the precise underlying mechanisms remain unclear. Here, we report a protein kinase C-ɛ (PKCɛ)- and ATF2-mediated mechanism that facilitates resistance by transcriptionally repressing the expression of interferon-ß1 (IFNß1) and downstream type-I IFN signaling that is otherwise induced upon exposure to chemotherapy. Treatment of early-stage melanomas expressing low levels of PKCɛ with chemotherapies relieves ATF2-mediated transcriptional repression of IFNß1, resulting in impaired S-phase progression, a senescence-like phenotype and increased cell death. This response is lost in late-stage metastatic melanomas expressing high levels of PKCɛ. Notably, nuclear ATF2 and low expression of IFNß1 in melanoma tumor samples correlates with poor patient responsiveness to biochemotherapy or neoadjuvant IFN-α2a. Conversely, cytosolic ATF2 and induction of IFNß1 coincides with therapeutic responsiveness. Collectively, we identify an IFNß1-dependent, cell-autonomous mechanism that contributes to the therapeutic resistance of melanoma via the PKCɛ-ATF2 regulatory axis.

Histochemical evaluation of catechins in PEG stressed transgenic tea plants using catechin-specific-diazotized sulfanilamide reagent.

We investigated the applicability of catechin-specific-reagent (CSR) for histochemical evaluation of catechins. The diazotized arylamine moiety in CSR reacts specifically with the A-ring of catechins to yield a golden yellow complex. This makes it highly specific for spectrophotometric quantification of catechins. Therefore, microtome cut sections of untransformed and osmotin-expressing transgenic leaves and stem of tea were stained with CSR. We found catechins in the form of golden yellow globules. The catechin globules increased in the structurally intact and highly turgid cells of osmotin expressing transgenic tea plants after stress treatment with 20% PEG; by contrast, the cells in non-transgenic plants accumulated fewer catechin globules. Spectrophotometric quantification of catechins also confirmed higher levels in transgenics compared to untransformed plants. We found elevated accumulation of catechins in stress tolerant cells of tea leaves.

Metabolic syndrome is a risk factor for development of heart failure in acute myocardial infarction.

There is a relationship between metabolic syndrome with heart failure. A case control study was designed to see the association of metabolic syndrome with heart failure. The study was conducted from August 2009 to May 2010. Hundred cases were selected as study population which was taken from Department of Cardiology Mymensingh Medical College, Mymensingh. Among them 50 were in Group A, 50 were in Group B. Group A was the patient with acute myocardial infarction (AMI) with metabolic syndrome. Group B was the patient with AMI without metabolic syndrome. It revealed that 23(46%) in Group A and 10 (20%) in Group B developed heart failure. Which is statistically significant (p<0.05). The study concluded that metabolic syndrome is significantly associated with heart failure.

Long-term survival in an un-operated single ventricle.

Single ventricle is a rare and complex congenital heart disease. Neonates with single ventricle have a high mortality. Survival into adulthood is rare without surgical intervention. A case of single ventricle with double inlet and double outlet combined with severe valvular pulmonary stenosis and mitral regurgitation (Grade II) is being reported here. A 36 years old man was admitted for bluish discoloration of lips, tongue and fingers; shortness of breath and recurrent palpitation. His ECG showed atrial fibrillation with fast ventricular rate. Chest X-Ray depicted an enlarged cardiac shadow and right sided pleural effusion. Final diagnosis was made by echocardiogram which demonstrated single ventricle with double inlet and double outlet, severe valvular pulmonary stenosis and mitral regurgitation (Grade II) with good ventricular systolic function.

Disseminated tuberculosis presenting as acute coronary syndrome.

Tuberculosis is a major public health problem in Bangladesh. Though tuberculosis is common but acute myopericarditis can rarely be caused by tuberculosis infection. A case of disseminated tuberculosis presenting with features of acute coronary syndrome is presenting here. A 26 years old man was admitted for severe central chest pain for 2 days and fever for 2 months. His ECG showed ST segment elevation in chest leads, V1 to V4 with elevated Troponin I and high ESR. Chest X-Ray depicted an enlarged cardiac shadow. Echocardiography demonstrated multiple dynamic cavitary lesions involving interventricular septum as well as anterior wall of the left ventricle within myocardium with moderate pericardial effusion with trivial mitral regurgitation. A CT scan of chest with contrast revealed multiple calcific communicating cavities within endocardium and myocardium involving interventricular septum and anterior wall of the left ventricle of heart and multiple cavitary lesions in the mid zone of left lung with bilateral mild pleural effusion. The patient made an excellent recovery on management of acute coronary syndrome and on antitubercular therapy.

A case report of right ventricular mass.

Primary Cardiac tumors are uncommon during infancy and childhood. Myxomas originating in the right ventricles are even less common in paediatric patient. Our patient baby Rani, 3 months of age presented with shortness of breath and chest indrawing. Antenatal history and delivery was uneventful. The baby was under weight and also malnourished but there was no cyanosis and clubbing. Her respiratory rate was 25/minute. On precordium examination, first heart sound (S1) was normal but pulmonary component of second heart sound (P2) was soft. There was an ejection systolic murmur (Grade-3/6) in the left upper para-sternal area. Chest X-ray revealed cardiomegaly. Echocardiogram revealed a large mass (11x10mm) in the right ventricle, dynamically obstructing the right ventricular out-flow tract and compressing the left ventricle. There was a Tricuspid regurgitation (Grade-2) and moderate pulmonary hypertension (PASP-50 mmHg).

Requirement for Pbx1 in skeletal patterning and programming chondrocyte proliferation and differentiation.

Pbx1 and a subset of homeodomain proteins collaboratively bind DNA as higher-order molecular complexes with unknown consequences for mammalian development. Pbx1 contributions were investigated through characterization of Pbx1-deficient mice. Pbx1 mutants died at embryonic day 15/16 with severe hypoplasia or aplasia of multiple organs and widespread patterning defects of the axial and appendicular skeleton. An obligatory role for Pbx1 in limb axis patterning was apparent from malformations of proximal skeletal elements, but distal structures were unaffected. In addition to multiple rib and vertebral malformations, neural crest cell-derived skeletal structures of the second branchial arch were morphologically transformed into elements reminiscent of first arch-derived cartilages. Although the skeletal malformations did not phenocopy single or compound Hox gene defects, they were restricted to domains specified by Hox proteins bearing Pbx dimerization motifs and unaccompanied by alterations in Hox gene expression. In affected domains of limbs and ribs, chondrocyte proliferation was markedly diminished and there was a notable increase of hypertrophic chondrocytes, accompanied by premature ossification of bone. The pattern of expression of genes known to regulate chondrocyte differentiation was not perturbed in Pbx1-deficient cartilage at early days of embryonic skeletogenesis, however precocious expression of Col1a1, a marker of bone formation, was found. These studies demonstrate a role for Pbx1 in multiple developmental programs and reveal a novel function in co-ordinating the extent and/or timing of proliferation with terminal differentiation. This impacts on the rate of endochondral ossification and bone formation and suggests a mechanistic basis for most of the observed skeletal malformations.

Cocaine and D-amphetamine induce changes in central beta-adrenoceptor sensitivity: effects of acute and chronic drug treatment.

The effects of acute and chronic treatment with psychomotor stimulants on specific binding of [3H]dihydroalprenolol to beta-adrenoceptors in rat brain were examined. At a dose of 10 mg/kg both acute and chronic treatment with cocaine and chronic treatment with D-amphetamine (10 mg/kg) caused increased binding of [3H]dihydroalprenolol. The molecular mechanism for this enhanced binding appears to be augmentation of the density of beta-adrenoceptors in rat brain. At a lower dose (5 mg/kg), however, chronic administration of D-amphetamine caused a decrease in the density of beta-adrenoceptors in rat brain. Chronic treatment with either D-amphetamine (10 mg/kg) or cocaine induced a marked increase in the magnitude of cyclic AMP accumulation in rat brain slices elicited by norepinephrine. Acute as well as chronic administration of D-amphetamine in vivo inhibited the temperature-dependent uptake of [3H]norepinephrine in rat brain synaptosomal homogenates, but no such inhibition was observed after chronic or acute treatment with cocaine. The results suggest that psychomotor stimulants induce beta-adrenoceptor supersensitivity which may be involved in the phenomenon of reverse tolerance and possibly psychosis in humans. The development of beta-adrenoceptor supersensitivity does not appear to be mediated through alterations in norepinephrine transport at the presynaptic sites.

High total histone deoxyribonucleic acid ratios for rat liver nuclei.

The ratios of total histone to DNA for rat liver nuclei isolated by four methods as well as for calf liver nuclei isolated by one method were determined by obtaining the ratios of the total areas of the electrophoretic histone peaks for the liver nuclei to the corresponding total area given by a known amount of standard calf thymus histone. Ratios of total histone to DNA of approx. 2 for rat liver nuclei isolated at pH3.8 or 5.8 and for calf liver nuclei isolated at pH3.8 were confirmed twice by the above procedure and also by direct measurement, by the method of Lowry et al. (1951), of histone extracted in 0.2m-H(2)SO(4). The histones of calf thymus, calf liver and rat liver were characterized by their amino acid compositions and by polyacrylamide-gel electrophoresis.