Primary non-Hodgkin's lymphoma of breast – A rare cause of breast lump

AbstractWe, here, report a case of primary breast lymphoma in a 59years old female. The diagnosis was suspected on fine needle aspiration cytology and confirmed on excision biopsy of the tumor. Histology and immunophenotyping were in accordance with non-Hodgkin's diffuse large B-cell lymphoma. The patient has been planned for adjuvant chemoradiation. The management and outcome of primary breast lymphoma and carcinoma are totally different. Early and prompt diagnosis of primary breast lymphoma is of utmost importance to avoid unnecessary mastectomies. Fine needle aspiration cytology supplemented by immuno-cytochemistry can be applied as a reliable and cost-effective tool in the early diagnosis of primary breast lymphomas, while histopathology and immunohistochemistry are conclusive

N-Terminal Phosphorylation of the Dopamine Transporter Is Required for Amphetamine-Induced Efflux

Amphetamine (AMPH) elicits its behavioral effects by acting on the dopamine (DA) transporter (DAT) to induce DA efflux into the synaptic cleft. We previously demonstrated that a human DAT construct in which the first 22 amino acids were truncated was not phosphorylated by activation of protein kinase C, in contrast to wild-type (WT) DAT, which was phosphorylated. Nonetheless, in all functions tested to date, which include uptake, inhibitor binding, oligomerization, and redistribution away from the cell surface in response to protein kinase C activation, the truncated DAT was indistinguishable from the full-length WT DAT. Here, however, we show that in HEK-293 cells stably expressing an N-terminal-truncated DAT (del-22 DAT), AMPH-induced DA efflux is reduced by approximately 80%, whether measured by superfusion of a population of cells or by amperometry combined with the patch-clamp technique in the whole cell configuration. We further demonstrate in a full-length DAT construct that simultaneous mutation of the five N-terminal serine residues to alanine (S/A) produces the same phenotype as del-22—normal uptake but dramatically impaired efflux. In contrast, simultaneous mutation of these same five serines to aspartate (S/D) to simulate phosphorylation results in normal AMPH-induced DA efflux and uptake. In the S/A background, the single mutation to Asp of residue 7 or residue 12 restored a significant fraction of WT efflux, whereas mutation to Asp of residues 2, 4, or 13 was without significant effect on efflux. We propose that phosphorylation of one or more serines in the N-terminus of human DAT, most likely Ser7 or Ser12, is essential for AMPH-induced DAT-mediated DA efflux. Quite surprisingly, N-terminal phosphorylation shifts DAT from a “reluctant” state to a “willing” state for AMPH-induced DA efflux, without affecting inward transport. These data raise the therapeutic possibility of interfering selectively with AMPH-induced DA efflux without altering physiological DA uptake

3D genomics across the tree of life reveals condensin II as a determinant of architecture type

We investigated genome folding across the eukaryotic tree of life. We find two types of three-dimensional(3D) genome architectures at the chromosome scale. Each type appears and disappears repeatedlyduring eukaryotic evolution. The type of genome architecture that an organism exhibits correlates with theabsence of condensin II subunits. Moreover, condensin II depletion converts the architecture of thehuman genome to a state resembling that seen in organisms such as fungi or mosquitoes. In this state,centromeres cluster together at nucleoli, and heterochromatin domains merge. We propose a physicalmodel in which lengthwise compaction of chromosomes by condensin II during mitosis determineschromosome-scale genome architecture, with effects that are retained during the subsequent interphase.This mechanism likely has been conserved since the last common ancestor of all eukaryotes.C.H. is supported by the Boehringer Ingelheim Fonds; C.H., Á.S.C., and B.D.R. are supported by an ERC CoG (772471, “CohesinLooping”); A.M.O.E. and B.D.R. are supported by the Dutch Research Council (NWO-Echo); and J.A.R. and R.H.M. are supported by the Dutch Cancer Society (KWF). T.v.S. and B.v.S. are supported by NIH Common Fund “4D Nucleome” Program grant U54DK107965. H.T. and E.d.W. are supported by an ERC StG (637597, “HAP-PHEN”). J.A.R., T.v.S., H.T., R.H.M., B.v.S., and E.d.W. are part of the Oncode Institute, which is partly financed by the Dutch Cancer Society. Work at the Center for Theoretical Biological Physics is sponsored by the NSF (grants PHY-2019745 and CHE-1614101) and by the Welch Foundation (grant C-1792). V.G.C. is funded by FAPESP (São Paulo State Research Foundation and Higher Education Personnel) grants 2016/13998-8 and 2017/09662-7. J.N.O. is a CPRIT Scholar in Cancer Research. E.L.A. was supported by an NSF Physics Frontiers Center Award (PHY-2019745), the Welch Foundation (Q-1866), a USDA Agriculture and Food Research Initiative grant (2017-05741), the Behavioral Plasticity Research Institute (NSF DBI-2021795), and an NIH Encyclopedia of DNA Elements Mapping Center Award (UM1HG009375). Hi-C data for the 24 species were created by the DNA Zoo Consortium (www.dnazoo.org). DNA Zoo is supported by Illumina, Inc.; IBM; and the Pawsey Supercomputing Center. P.K. is supported by the University of Western Australia. L.L.M. was supported by NIH (1R01NS114491) and NSF awards (1557923, 1548121, and 1645219) and the Human Frontiers Science Program (RGP0060/2017). The draft A. californica project was supported by NHGRI. J.L.G.-S. received funding from the ERC (grant agreement no. 740041), the Spanish Ministerio de Economía y Competitividad (grant no. BFU2016-74961-P), and the institutional grant Unidad de Excelencia María de Maeztu (MDM-2016-0687). R.D.K. is supported by NIH grant RO1DK121366. V.H. is supported by NIH grant NIH1P41HD071837. K.M. is supported by a MEXT grant (20H05936). M.C.W. is supported by the NIH grants R01AG045183, R01AT009050, R01AG062257, and DP1DK113644 and by the Welch Foundation. E.F. was supported by NHGR

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension

Developmental changes in the membrane fatty acids of rats and the role of the thyroid

The role of the thyroid in developmental changes in membrane fatty acids was examined in the rat. Three tissues were studied in euthyroid and hypothyroid rats, the tissues were liver, heart and brain. Hypothyroidism was acheived by providing pregnant and young rats with drinking water containing 0.05% PTU. Both euthyroid and hypothyroid rats were killed at 1, 5, 15 and 25 days of age as well as adult rats. The following parameters were measured in both groups ; plasma T^ and T3 concentrations, body weight, tissue weights, phospholipid content of tissues, fatty acid composition of phospholipids isolated from these tissues

Hormonal regulation of surfactant production in cultured fetal lung cells

Type II pneumocytes are responsible for the synthesis, storage and secretion of surfactant, a compound which lowers surface tension in the lung thus preventing alveolar collapse at end expiration. The rate of synthesis and secretion of the major surface-active component, disaturated phosphatidylcholine (DSPC), has been shown to be influenced by a number of agents. In this study it has been shown that epidermal growth factor (EGF) increases the rate of choline incorporation into DSPC by cultured fetal type II cells in a manner analogous to glucocorticoids. Whereas EGF has no effect on the rate of DSPC synthesis when added directly to type II pneumocytes, the growth factor is effective if it is present during preliminary conditioning of the media by lung fibroblasts. This effect is concentration dependent with a maximal effect at 20 ng. mL-1 and can be mimicked by the phorbol ester, phorbol 12-myristate 13-acetate (PMA), Although the calcium ionophore A23187 is without effect alone, it does enhance the stimulatory effect when added with PMA. These findings suggest that the response to EGF might well involve activation of protein kinase C. When lung fibroblasts are incubated with both glucocorticoids and EGF there is no significant effect of the growth factor over and above that seen with the steroid alone. This suggests that the two agents might act via a similar mechanism. This is supported by the observation that each inducer leads to the production by lung fibroblasts of a stimulatory factor which has a similar, if not identical, chromatographic elution profile. EGF has also been shown to interact directly with type II pneumocytes and, in a time- and concentration-dependent manner, enhances the rate of secretion of surfactant phospholipids. This effect was shown to be mimicked by either the calcium ionophore, A23187, or the protein kinase C activator, PMA. The positive response to A23187 on the rate of surfactant secretion is in contrast to the lack of response when surfactant synthesis was examined and suggests the elevated secretion rate in response to EGF probably involves both Ca2+ mobilization and protein kinase C activation. This study has also demonstrated that p-adrenergic receptors are present and functional in cultures enriched with fetal type II pneumocytes. Using the specific radioligand I-CYP, and both pi and P2 antagonists, it was established that the p2-subtype was the predominant p-adrenoceptor associated with fetal rat type II cells. Direct exposure of the type II cells to either fibroblast-conditioned media or glucocorticoids results in an elevation in the level of p-adrenoceptors. These conditions also lead to an enhanced response to the p-agonist, (—) -isoproterenol, as judged by a greater rate of phospholipid secretion, indicating a close link between the level of p-adrenoceptors and the extent to which p-agonists are able to stimulate surfactant secretion

The origin and early history of the Khasi-Synteng people.

This work consists of survey of the evidence on the origin of the Khasi-Synteng people and a review of their history, as far as it can be reconstructed, down to the latter part of the eighteenth century. This is followed by a review of their traditional culture, as it was before the opening up of the Khasi and Jaintia Hills. The work is thus divided into two main parts, preceded by an introduction discussing geography, sources and previous work on the subject, and ending with a conclusion, summarizing the contents of the thesis and briefly surveying the later history of the Khasi-Syntengs down to the present day. In the first part, Chapter II reviews the ethnology of the Khasi-Syntengs, and considers their connections with other ethnic groups in India and South-east Asia. This chapter also considers the evidence of the few Neolithic artifacts found in the region. The third chapter deals with the evidence of the megalithic structures in the Khasi and Jaintia Hills, and discusses possible relationship with other megalithic cultures. In the fourth chapter linguistic evidence is considered, from various points of view, and it is suggested from the evidence of loan-words that the earliest contact of the Khasis with Indo-Aryan speakers may have been later than previously supposed. The following three chapters cover the history of the Jaintia Kingdom, much of which can be traced in considerable detail from the early sixteenth century onwards, chiefly through the Assamese chronicles. The accounts of these are often conflicting in points of detail, and the thesis attempts to solve these conflicts of evidence wherever possible, and to present the most probable interpretation of the data. Little can be discovered about the history of the hill Khasis, but certain documents of the East India Company throw some light on their relations with the plains at the end of our period. These are considered in the eighth chapter. The second part of the thesis begins with a review of the system of government of the Khasi-Syntengs (Chapter IX). In the following chapter (X) the social institutions of the Khasi-Synteng tribes are dealt with, including the matrilineal of the Khasi-Synteng tribes are dealt with, including the matrilineal (but not matriarchal) family system, the tribal and clan structure, and the system of inheritance. Chapter XI, on religion, commences with a consideration of the Khasi high god, and it is shown that he is not bisexual, as believed by some anthropologists. The chapter rites, ideas of the belief in lesser gods and demons, sacrificial rites, ideas of the after-life and the practice of ancesding the complex megalithic rites in honour of the ancestors of the clan. In the twelfth chapter aspects of the trade, industry and agriculture of the Khasis are discussed. The thirteenth chapter, entitled 'Everyday Life' review various aspects of the life of the Khasi-Syntengs, such as houses and furniture, food and drink, dress, literature and music, games and sports, astronomy and medicine. The thesis concludes with appendices on the Jaintia king-list and the Assamese months