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141.
142.
Background
Prostate cancer is the single most prevalent cancer in US men whose gold standard of diagnosis is histologic assessment of biopsies. Manual assessment of stained tissue of all biopsies limits speed and accuracy in clinical practice and research of prostate cancer diagnosis. We sought to develop a fully-automated multimodal microscopy method to distinguish cancerous from non-cancerous tissue samples. 相似文献143.
EGLN1 involvement in high-altitude adaptation revealed through genetic analysis of extreme constitution types defined in Ayurveda 总被引:1,自引:0,他引:1
Aggarwal S Negi S Jha P Singh PK Stobdan T Pasha MA Ghosh S Agrawal A;Indian Genome Variation Consortium Prasher B Mukerji M 《Proceedings of the National Academy of Sciences of the United States of America》2010,107(44):18961-18966
It is being realized that identification of subgroups within normal controls corresponding to contrasting disease susceptibility is likely to lead to more effective predictive marker discovery. We have previously used the Ayurvedic concept of Prakriti, which relates to phenotypic differences in normal individuals, including response to external environment as well as susceptibility to diseases, to explore molecular differences between three contrasting Prakriti types: Vata, Pitta, and Kapha. EGLN1 was one among 251 differentially expressed genes between the Prakriti types. In the present study, we report a link between high-altitude adaptation and common variations rs479200 (C/T) and rs480902 (T/C) in the EGLN1 gene. Furthermore, the TT genotype of rs479200, which was more frequent in Kapha types and correlated with higher expression of EGLN1, was associated with patients suffering from high-altitude pulmonary edema, whereas it was present at a significantly lower frequency in Pitta and nearly absent in natives of high altitude. Analysis of Human Genome Diversity Panel-Centre d'Etude du Polymorphisme Humain (HGDP-CEPH) and Indian Genome Variation Consortium panels showed that disparate genetic lineages at high altitudes share the same ancestral allele (T) of rs480902 that is overrepresented in Pitta and positively correlated with altitude globally (P < 0.001), including in India. Thus, EGLN1 polymorphisms are associated with high-altitude adaptation, and a genotype rare in highlanders but overrepresented in a subgroup of normal lowlanders discernable by Ayurveda may confer increased risk for high-altitude pulmonary edema. 相似文献
144.
Anand Srivastava Stéphane Gangnard Adam Round Sébastien Dechavanne Alexandre Juillerat Bertrand Raynal Grazyna Faure Bruno Baron Stéphanie Ramboarina Saurabh Kumar Singh Hassan Belrhali Patrick England Anita Lewit-Bentley Artur Scherf Graham A. Bentley Beno?t Gamain 《Proceedings of the National Academy of Sciences of the United States of America》2010,107(11):4884-4889
Pregnancy-associated malaria (PAM) is a serious consequence of sequestration of Plasmodium falciparum-parasitized erythrocytes (PE) in the placenta through adhesion to chondroitin sulfate A (CSA) present on placental proteoglycans. Recent work implicates var2CSA, a member of the PfEMP1 family, as the mediator of placental sequestration and as a key target for PAM vaccine development. Var2CSA is a 350 kDa transmembrane protein, whose extracellular region includes six Duffy-binding-like (DBL) domains. Due to its size and high cysteine content, the full-length var2CSA extracellular region has not hitherto been expressed in heterologous systems, thus limiting investigations to individual recombinant domains. Here we report for the first time the expression of the full-length var2CSA extracellular region (domains DBL1X to DBL6ε) from the 3D7 parasite strain using the human embryonic kidney 293 cell line. We show that the recombinant extracellular var2CSA region is correctly folded and that, unlike the individual DBL domains, it binds with high affinity and specificity to CSA (KD = 61 nM) and efficiently inhibits PE from binding to CSA. Structural characterization by analytical ultracentrifugation and small-angle x-ray scattering reveals a compact organization of the full-length protein, most likely governed by specific interdomain interactions, rather than an extended structure. Collectively, these data suggest that a high-affinity, CSA-specific binding site is formed by the higher-order structure of the var2CSA extracellular region. These results have important consequences for the development of an effective vaccine and therapeutic inhibitors. 相似文献
145.
Dhawan SS 《The American journal of the medical sciences》2007,333(1):56-57
Presented here is a case of syndrome of inappropriate antidiuretic hormone secretion (SIADH) that developed in an elderly woman with single dermatomal herpes varicella zoster ophthalmicus without evidence of varicella-zoster encephalitis or dissemination. This is only the third such case reported in the English language literature to date, and it affirms that SIADH can develop in patients with herpetic involvement of just a single dermatome and corrects with resolution of the herpetic lesions. 相似文献
146.
Gupta S Lozano-Cuenca J Villalón CM de Vries R Garrelds IM Avezaat CJ van Kats JP Saxena PR MaassenVanDenBrink A 《Naunyn-Schmiedeberg's archives of pharmacology》2007,375(1):29-38
Capsaicin, a pungent constituent from red chilli peppers, activates sensory nerve fibres via transient receptor potential
vanilloid receptors type 1 (TRPV1) to release neuropeptides like calcitonin gene-related peptide (CGRP) and substance P. Capsaicin-sensitive
nerves are widely distributed in human and porcine vasculature. In this study, we examined the mechanism of capsaicin-induced
relaxations, with special emphasis on the role of CGRP, using various pharmacological tools. Segments of human and porcine
proximal and distal coronary arteries, as well as cranial arteries, were mounted in organ baths. Concentration response curves
to capsaicin were constructed in the absence or presence of the CGRP receptor antagonist olcegepant (BIBN4096BS, 1 μM), the
neurokinin NK1 receptor antagonist L-733060 (0.5 μM), the voltage-sensitive calcium channel blocker ruthenium red (100 μM), the TRPV1 receptor
antagonist capsazepine (5 μM), the nitric oxide synthetase inhibitor N
ω-nitro-l-arginine methyl ester HCl (l-NAME; 100 μM), the gap junction blocker 18α-glycyrrhetinic acid (10 μM), as well as the RhoA kinase inhibitor Y-27632 (1 μM).
Further, we also used the K+ channel inhibitors 4-aminopyridine (1 mM), charybdotoxin (0.5 μM) + apamin (0.1 μM) and iberiotoxin (0.5 μM) + apamin (0.1 μM).
The role of the endothelium was assessed by endothelial denudation in distal coronary artery segments. In distal coronary
artery segments, we also measured levels of cyclic adenosine monophosphate (cAMP) after exposure to capsaicin, and in human
segments, we also assessed the amount of CGRP released in the organ bath fluid after exposure to capsaicin. Capsaicin evoked
concentration-dependent relaxant responses in precontracted arteries, but none of the above-mentioned inhibitors did affect
these relaxations. There was no increase in the cAMP levels after exposure to capsaicin, unlike after (exogenously administered)
α-CGRP. Interestingly, there were significant increases in CGRP levels after exposure to vehicle (ethanol) as well as capsaicin,
although this did not induce relaxant responses. In conclusion, the capsaicin-induced relaxations of the human and porcine
distal coronary arteries are not mediated by CGRP, NK1, NO, vanilloid receptors, voltage-sensitive calcium channels, K+ channels or cAMP-mediated mechanisms. Therefore, these relaxant responses to capsaicin are likely to be attributed to a non-specific,
CGRP-independent mechanism. 相似文献
147.
Sabi Essa M. Singh Anuja Althafar Ziyad M. Behl Tapan Sehgal Aayush Singh Sukhbir Sharma Neelam Bhatia Saurabh Al-Harrasi Ahmed Alqahtani Hosam M. Bungau Simona 《Inflammopharmacology》2022,30(3):737-748
Inflammopharmacology - Rheumatoid arthritis (RA) is a chronic multifactorial disease, provocative, and degenerative autoimmune condition that impacts millions of individuals around the globe. As a... 相似文献
148.
A 57-year-old schizophrenic woman presented with lethargy, nausea, vomiting, and anorexia after coin ingestion. She was found to have multiple organ dysfunction manifested as hepatitis, pancreatitis, severe anemia with markedly depressed bone marrow response, extravascular hemolysis, and acute renal failure. Prolonged exposure to zinc from massive coin ingestion was responsible. Zinc poisoning is an unusual consequence of coin ingestion in the adult human literature. A detailed discussion on zinc poisoning, as well as the pitfalls in radiological diagnosis of massive coin ingestion, is presented. 相似文献
149.
Saurabh Bhargava Jacob M. Patterson Richard D. Inman Sheila MacNeil Christopher R. Chapple 《European urology》2008,53(6):1263-1271
Introduction
Whilst buccal mucosa is the most versatile tissue for urethral replacement, the quest continues for an ideal tissue replacement for the urethra when substantial tissue transfer is needed. Previously we described the development of autologous tissue-engineered buccal mucosa (TEBM). Here we report clinical outcomes of the first human series of its use in substitution urethroplasty.Methodology
Five patients with urethral stricture secondary to lichen sclerosus (LS) awaiting substantial substitution urethroplasty elected to undergo urethroplasty using TEBM, with full ethics committee support. Buccal mucosa biopsies (0.5 cm) were obtained from each patient. Keratinocytes and fibroblasts were isolated and cultured, seeded onto sterilised donor de-epidermised dermis, and maintained at air–liquid interface for 7–10 d to obtain full-thickness grafts. These grafts were used for urethroplasty in a one-stage (n = 2) or a two-stage procedure (n = 3). Follow-up was performed at 2 and 6 wk, at 3, 6, 9, and 12 mo, and every 6 mo thereafter.Results
Follow-up ranged from 32 to 37 mo (mean, 33.6). The initial graft take was 100%, as assessed by visual inspection. Subsequently, one patient had complete excision of the grafted urethra and one required partial graft excision, for fibrosis and hyperproliferation of tissue, respectively. Three patients have a patent urethra with the TEBM graft in situ, although all three required some form of instrumentation.Conclusions
Whilst TEBM may in the future offer a clinically useful autologous urethral replacement tissue, in this group of patients with LS urethral strictures, it was not without complications, namely fibrosis and contraction in two of five patients. 相似文献150.
Kumar S Pandya S Singh SK Panigrahy B Acharya N Lal A Mandal AK 《Journal of endourology / Endourological Society》2008,22(5):979-983
L-shaped fused ectopic kidney is a rare variant of crossed fused renal ectopia. We describe a case of crossed fused L-shaped kidney with congenital ureteropelvic junction obstruction involving an orthotopically located kidney presenting as renal trauma, and its management by laparoscopic heminephrectomy. 相似文献