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51.
Harmanjot?Kaur Shanti?Choudhary Devendra?Pathak Opinder?Singh Ramneek?Verma Ratan?K.?ChoudharyEmail author 《Proceedings of the National Academy of Sciences, India. Section B.》2018,88(1):23-32
Water buffaloes are the principle source of milk in south Asia and Africa. Mammary gland repeatedly undergoes the cycles of growth and regeneration during pregnancy, lactation and involution. It is assumed that buffalo mammary gland has mammary stem and progenitor cells that regulate gland growth and regeneration. In the present study the authors analyzed percentage of cellular composition, proliferation status and putative mammary stem/progenitor cell population. Identification of putative buffalo mammary stem/progenitor cells was attempted using immunohistochemical staining with Musashi1 (MSI1), an adult stem cell marker and fibronectin type III domain containing 3B (FNDC3B), a mammary stem and cancer cell marker. Immunolocalization of MSI1 and FNDC3B showed nuclear and cytoplasmic staining of alveolar and ductal mammary epithelial cells (MEC) and a few stromal cells. The percentage of MSI1-positive MEC in non-lactating (3.31 ± 1.11 %), lactating (2.73 ± 0.78 %) and mastitic glands (3.30 ± 0.97 %) were equivalent, indicating that the proportion of putative stem/progenitor cell population did not differ during various physiological stages. Likewise, the percentage of FNDC3B-positive MEC in non-lactating (12.40 ± 3.22 %) tended to be higher than lactating (8.19 ± 2.71 %) and mastitic glands (4.88 ± 2.37 %). In some cases, expression of MSI1 and FNDC3B was exceptionally high with high proliferative indices (37.6 ± 2.4 %)-an indication of tumor cells. This is the first report on expression of MSI1 and FNDC3B in buffalo mammary gland. Identification of buffalo mammary stem cells using MSI1 and FNDC3B requires further studies and functional validation. 相似文献
52.
Suneet Kaur Gautam Srivastava Amar Nath Sharma Ravinder S Jolly 《British journal of pharmacology》2015,172(9):2286-2299
Background and Purpose
Recently, we have described the use of caerulomycin A (CaeA) as a potent novel immunosuppressive agent. Immunosuppressive drugs are crucial for long-term graft survival following organ transplantation and treatment of autoimmune diseases, inflammatory disorders, hypersensitivity to allergens, etc. The objective of this study was to identify cellular targets of CaeA and decipher its mechanism of action.Experimental Approach
Jurkat cells were treated with CaeA and cellular iron content, iron uptake/release, DNA content and deoxyribonucleoside triphosphate pool determined. Activation of MAPKs; expression level of transferrin receptor 1, ferritin and cell cycle control molecules; reactive oxygen species (ROS) and cell viability were measured using Western blotting, qRT-PCR or flow cytometry.Key Results
CaeA caused intracellular iron depletion by reducing its uptake and increasing its release by cells. CaeA caused cell cycle arrest by (i) inhibiting ribonucleotide reductase (RNR) enzyme, which catalyses the rate-limiting step in the synthesis of DNA; (ii) stimulating MAPKs signalling transduction pathways that play an important role in cell growth, proliferation and differentiation; and (iii) by targeting cell cycle control molecules such as cyclin D1, cyclin-dependent kinase 4 and p21CIP1/WAF1. The effect of CaeA on cell proliferation was reversible.Conclusions and Implications
CaeA exerts its immunosuppressive effect by targeting iron. The effect is reversible, which makes CaeA an attractive candidate for development as a potent immunosuppressive drug, but also indicates that iron chelation can be used as a rationale approach to selectively suppress the immune system, because compared with normal cells, rapidly proliferating cells require a higher utilization of iron. 相似文献53.
Bhatti Gurjit Kaur Khullar Naina Sidhu Inderpal Singh Navik Uma Shanker Reddy Arubala P. Reddy P. Hemachandra Bhatti Jasvinder Singh 《Metabolic brain disease》2021,36(6):1119-1134
Metabolic Brain Disease - Human diseases have always been a significant turf of concern since the origin of mankind. It is cardinal to know the cause, treatment, and cure for every disease... 相似文献
54.
Gagan Kaur Patrick Baghdasaryan Balaji Natarajan Prabhdeep Sethi Ashis Mukherjee Padmini Varadarajan Ramdas G. Pai 《The International journal of angiology》2021,30(1):15
Coronary no-reflow phenomenon is a lethal mechanism of ongoing myocardial injury, following successful revascularization of an infarct-related coronary artery. Incidence of this phenomenon is high following percutaneous intervention, and is associated with adverse in-hospital and long-term outcomes. Several mechanisms such as ischemia-reperfusion injury and distal microthromboembolism in genetically susceptible patients and those with preexisting endothelial dysfunction have been implicated. However, the exact mechanism in humans is still poorly understood. Several investigative and treatment strategies within and outside the cardiac catheterization laboratory have been proposed, but have not uniformly shown success in reducing mortality or in preventing adverse left ventricular remodeling resulting from this condition. The aim of this article is to provide a brief and concise review of the current understanding of the pathophysiology, clinical predictors, and investigations and management of coronary no-reflow phenomenon. 相似文献
55.
The rising prevalence of the chronic obstructive pulmonary disease (COPD) is generally attributed to smoking, since the role of other risk factors among non-smokers are not well established especially in low and middle income countries like India. This is also reflected by the limited literature available on non-smoking related COPD risk factors like indoor and outdoor air pollution. The present review is an attempt to assess the influence of non-smoking risk factors on COPD and its measures in Indian subcontinent. The most noteworthy factors among non-smokers appear to be the use of biomass fuel for cooking and heating purposes. We observed that the studies undertaken to evaluate the role of such risk factors are inconclusive due to weak methodologies and small sample sizes, may be due to limited financial resources. The present review suggests the need of a nationally representative study to estimate the effect of each of the potential modifiable risk factor (other than smoking) for framing impactful public health policies to prevent and manage COPD at community and population level in India. 相似文献
56.
Tani H Morris RJ Kaur P 《Proceedings of the National Academy of Sciences of the United States of America》2000,97(20):10960-10965
The identification and physical isolation of epithelial stem cells is critical to our understanding of their growth regulation during homeostasis, wound healing, and carcinogenesis. These stem cells remain poorly characterized because of the absence of specific molecular markers that permit us to distinguish them from their progeny, the transit amplifying (TA) cells, which have a more restricted proliferative potential. Cell kinetic analyses have permitted the identification of murine keratinocyte stem cells (KSCs) as slowly cycling cells that retain [(3)H]thymidine ([(3)H]Tdr) label, termed label-retaining cells (LRCs), whereas TA cells are visualized as rapidly cycling cells after a single pulse of [(3)H]Tdr, termed pulse-labeled cells (PLCs). Here, we report on the successful separation of KSCs from TA cells through the combined use of in vivo cell kinetic analysis and fluorescence-activated cell sorting. Specifically, we demonstrate that murine dorsal keratinocytes characterized by their high levels of alpha(6) integrin and low to undetectable expression of the transferrin receptor (CD71) termed alpha(6)(bri)CD71(dim) cells, are enriched for epithelial stem cells because they represent a minor ( approximately 8%) and quiescent subpopulation of small blast-like cells, with a high nuclear:cytoplasmic ratio, containing approximately 70% of label-retaining cells, the latter being a well documented characteristic of stem cells. Conversely, TA cells could be enriched in a phenotypically distinct subpopulation termed alpha(6)(bri)CD71(bri), representing the majority ( approximately 60%) of basal keratinocytes that are actively cycling, and importantly contain approximately 70% of [(3)H]Tdr pulse-labeled cells. Importantly, immunostaining of dorsal skin revealed the presence of CD71(dim) cells in the hair follicle bulge region, a well documented location for KSCs. 相似文献
57.
We report a patient with splenic vein thrombosis (SVT) in whom splenectomy resulted in the unmasking of essential thrombocythemia (ET). He had portal hypertension with haematemesis, resulting in anaemia requiring repeated blood transfusions. Investigations revealed SVT. Following splenectomy, he suffered a transient ischaemic attack episode, associated with persistent thrombocytosis (> 2000 x 10(9)/l). Other myeloproliferative disorders were excluded and a diagnosis of ET was established. He responded to hydroxyurea but, due to financial constraints, he discontinued treatment and subsequently relapsed. The association of ET with SVT is rare and the diagnosis of ET was missed initially as the platelet count was normal prior to splenectomy. 相似文献
58.
PURPOSE: Prediction of success after anterior sphincter repair
for incontinence is difficult. Standard multivariate
analysis techniques have only 75 to 80 percent accuracy.
Artificial intelligence, including artificial neural networks,
has been used in the analysis of complex clinical data and
has proved to be successful in predicting the outcome of
other surgical procedures. Using a neural network algorithm,
we have assessed the probability of success after
anterior sphincter repair. METHODS: Prospective anorectal
physiology data of 72 patients undergoing anterior sphincter
repair was collected between 1995 and 1999. Complete
data sets of 75 percent of the series were used to train an
artificial neural network; the remaining 25 percent were
used for data validation. The output was continence grading,
ranging from 0 to 4 (worse to continent). RESULTS: The
outcome at 3, 6, and 12 months postoperatively was obtained
and assessed. The best correlation between actual
data value and artificial neural network value was found at
12 months (r = 0.931; P = 0.0001). Clear correlations also
were found at three months (r = 0.898; P = 0.0001) and six
months (r = 0.742; P = 0.002). Results of applying a net to
details excluding pudendal nerve latency were poor. CONCLUSIONS:
Artificial neural networks are more accurate (93
percent correlation) than standard statistics (75 percent)
when applied to the prediction of outcome after anterior
sphincter repair. This assessment also confirms the usefulness
of pudendal latency in the prediction of anterior
sphincter repair outcome. The results obtained highlight
the obvious usefulness of artificial neural networks, which
could now be used in a prospective evaluation for application
of the technique. 相似文献
59.
Endothelins, a family of peptides derived from the vascular endothelium and smooth muscle cells possess vasoconstrictor and mitogenic properties. By acting predominantly in a paracrine fashion, these peptides activate specific receptors and have protean effects in normal and diseased organ systems. The wide distribution of these receptors in various tissues mediate the multiplicity of physiologic actions attributed to endothelins. Much of our understanding about endothelins has come from the development of an array of receptor-specific and mixed receptor antagonists. Based on the promising results from animal studies, active research and drug development programs are under way to investigate the clinical potential of endothelin antagonism for treatment of cardiovascular disease. 相似文献
60.
SETTING: Serum amyloid P-component (SAP) plays important roles in host defense during various infectious diseases; however, nothing is known in tuberculosis (TB). OBJECTIVE: To study the SAP response of Mycobacterium tuberculosis H37Rv- and H37Ra-infected mice, and to determine the effect(s) of purified mouse SAP both on their intra-alveolar macrophage (AM) uptake and intra-AM growth in vitro. DESIGN: The SAP levels of mice intratracheally infected with M. tuberculosis H37Rv and H37Ra were determined by ELISA. Mycobacterial AM uptake and intra-AM growth in vitro were determined using fluorescence microscopy and plating, respectively. RESULTS: M. tuberculosis H37Rv-infected mice showed significantly (p < 0.05) increased SAP levels (352.8+/-36.1 microg/ml) with compared mice infected with M. tuberculosis H37Ra (170+/-18.5 microg/ml). During the acute phase of both these infections, enhanced SAP levels correlated with the lung mycobacterial load. In vitro, purified mouse SAP (1-80 microg/ml) inhibited the AM uptake of both the mycobacteria in a concentration-dependent manners to a similar extent; 20 microg/ml SAP appeared optimal. Mycobacterial uptake inhibition was divalent cation- and pH-dependent, and was unaffected both by heat-inactivated and deglycosylated SAP, separately. Curiously, purified mouse SAP (1-80 microg/ml), in a concentration-dependent manner, inhibited the intra-AM growth of both M. tuberculosis H37Rv and H37Ra in vitro; the effect was 0.8 log10 CFUs greater on the latter. Both the mannose-based simple sugars and rabbit anti-mouse SAP polyclonal antibody, separately, annulled the inhibition of mycobacterial growth in vitro. CONCLUSION: This initial study demonstrates that both the SAP response of M. tuberculosis-infected mice, and the SAP-induced intra-AM mycobacterial growth inhibition in vitro were apparently dependent on mycobacterial virulence. 相似文献