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981.
Harsh Kumar Pradeep Kumar Balasubramanian Narasimhan Kalavathy Ramasamy Vasudevan Mani Rakesh Kumar Mishra Abu Bakar Abdul Majeed 《Medicinal chemistry research》2013,22(4):1957-1971
In this study, N-(substituted phenyl)-2/4-(1H-indol-3-ylazo)-benzamides (1–26) were synthesized and screened for their in vitro antibacterial (Gram positive; S. aureus, B. subtilis and Gram negative; E. coli) and antifungal (C. albicans and A. niger) activities. The antimicrobial activity results indicated that compound, 4-(1H-indol-3-ylazo)-N-(4-nitro-phenyl)-benzamide (12, pMICam = 1.61) was the most potent. In general, it was found that the synthesized compounds were bacteriostatic/fungistatic in action except fungicidal for A. niger. The synthesized compounds were also evaluated for their antiproliferative activity against human colon cancer (HCT116), murine leukemia (P388), and breast cancer (MCF7) cell lines. The antiproliferative study results demonstrated 4-(1H-indol-3-ylazo)-N-p-tolyl-benzamide (2, IC50 = 0.0003 μM/mL) and 4-(1H-indol-3-ylazo)-N-p-tolyl-benzamide (21, 0.0003 μM/mL) as lead compounds for the development of novel antiproliferative agents. The QSAR studies indicated the importance of topological parameters, Kier’s alpha second-order shape indice (κα2) and Wiener index (W) in describing the antimicrobial activity of the synthesized compounds. 相似文献
982.
Tumours of the renal pelvis are rare. We present a case of primary mucinous adenocarcinoma of the renal pelvis masquerading as pyonephrosis clinically and diagnosed on histopathologic examination. Patient presented with pyonephrosis of the left kidney due to a large staghorn calculus and was treated with tube nephrostomy followed by nephrectomy. 相似文献
983.
This study was undertaken to highlight the use of fine needle aspiration cytology (FNAC) to distinguish tumours metastatic to the breast from primary breast malignancies. A total of 1866 fine needle aspirates of the breast were performed during a period of 7 years. Three hundred and fourteen cases of breast malignancies were diagnosed and 5 (1.5%) out of these cases were metastatic in origin. The metastatic tumors included, 2 cases of malignant melanoma (chest wall and left arm), 1 case each of haematolymphoid malignancy, adenocarcinoma of the ovary, and squamous cell carcinoma (left leg). FNA diagnosis of metastasis to the breast is essential in order to avoid unnecessary mastectomy and to ensure appropriate chemotherapy and/or irradiation treatment. 相似文献
984.
Richard Gallon Barbara Mühlegger Sren‐Sebastian Wenzel Harsh Sheth Christine Hayes Stefan Aretz Karin Dahan William Foulkes Christian P. Kratz Tim Ripperger Amedeo A. Azizi Hagit Baris Feldman Anne‐Laure Chong Ugur Demirsoy Benoît Florkin Thomas Imschweiler Danuta Januszkiewicz‐Lewandowska Stephan Lobitz Michaela Nathrath Hans‐Jürgen Pander Vanesa Perez‐Alonso Claudia Perne Iman Ragab Thorsten Rosenbaum Daniel Rueda Markus G. Seidel Manon Suerink Julia Taeubner Stefanie‐Yvonne Zimmermann Johannes Zschocke Gillian M. Borthwick John Burn Michael S. Jackson Mauro Santibanez‐Koref Katharina Wimmer 《Human mutation》2019,40(5):649-655
Constitutional mismatch repair deficiency (CMMRD) is caused by germline pathogenic variants in both alleles of a mismatch repair gene. Patients have an exceptionally high risk of numerous pediatric malignancies and benefit from surveillance and adjusted treatment. The diversity of its manifestation, and ambiguous genotyping results, particularly from PMS2, can complicate diagnosis and preclude timely patient management. Assessment of low‐level microsatellite instability in nonneoplastic tissues can detect CMMRD, but current techniques are laborious or of limited sensitivity. Here, we present a simple, scalable CMMRD diagnostic assay. It uses sequencing and molecular barcodes to detect low‐frequency microsatellite variants in peripheral blood leukocytes and classifies samples using variant frequencies. We tested 30 samples from 26 genetically‐confirmed CMMRD patients, and samples from 94 controls and 40 Lynch syndrome patients. All samples were correctly classified, except one from a CMMRD patient recovering from aplasia. However, additional samples from this same patient tested positive for CMMRD. The assay also confirmed CMMRD in six suspected patients. The assay is suitable for both rapid CMMRD diagnosis within clinical decision windows and scalable screening of at‐risk populations. Its deployment will improve patient care, and better define the prevalence and phenotype of this likely underreported cancer syndrome. 相似文献
985.
Anupama Gupta Harsh K. Verma Savita Gupta 《Medical & biological engineering & computing》2013,51(9):1043-1050
Stroke is the third major cause of death worldwide behind heart disease and cancer. Carotid atherosclerosis is the most frequent cause of ischemic stroke. Early diagnosis of carotid plaque and serial monitoring of its size with the help of imaging modalities can help to prevent the atherosclerotic complications. The main difficulty is inevitable variability of patient’s head positions during image acquisitions. The time series registration of carotid images helps to improve the monitoring, characterization, and quantification of the disease by suppressing the global movements of the patient. In this work, a novel hybrid registration technique has been proposed and evaluated for registration of carotid ultrasound images taken at different times. The proposed hybrid method bridges the gap between the feature-based and intensity-based registration methods. The feature-based iterative closest point algorithm is used to provide a coarse registration which is subsequently refined by the intensity-based algorithm. The proposed framework uses rigid transformation model coupled with mutual information (MI) similarity measure and Powell optimizer. For quantitative evaluation, different registration approaches have been compared using four error metrics: visual information fidelity, structural similarity index, correlation coefficient, and MI. Qualitative evaluation has also been done using the visual examination of the registered image pairs. 相似文献
986.
Harsh Goel Ashish Kumar Nadish Garg James D. Mills 《Trends in Cardiovascular Medicine》2021,31(1):34-46
Females suffer higher operative (30-day) mortality than males after surgical aortic valve replacement (SAVR). In contrast, outcomes after trans-catheter aortic valve replacement (TAVR) seem to favor females, both in terms of procedural mortality, and more prominently, medium to long-term survival. With an ever-greater number of TAVR procedures being performed, an understanding of factors responsible for gender differences in outcomes after the two AVR modalities is critical for better patient selection. Current evidence suggests that this gender difference in outcomes after SAVR and TAVR stems from differences in baseline risk profiles, as well as inherent anatomic/physiological differences between genders. This review attempts to examine these clinical and physiological factors, with a goal of guiding better patient selection for each AVR modality, and to highlight areas that beg further investigation. 相似文献
987.
Harsh Panwar Danielle Calderwood Irene R. Grant Sunita Grover Brian D. Green 《European journal of nutrition》2014,53(7):1465-1474
Purpose
Inhibitors of intestinal alpha-glucosidases are used therapeutically to treat type 2 diabetes mellitus. Bacteria such as Actinoplanes sp. naturally produce potent alpha-glucosidase inhibitor compounds, including the most widely available drug acarbose. It is not known whether lactic acid bacteria (LAB) colonising the human gut possess inhibitory potential against glucosidases. Hence, the study was undertaken to screen LABs having inherent alpha- and beta-glucosidase inhibitory potential.Methods
This study isolated, screened, identified and extracted Lactobacillus strains (Lb1–15) from human infant faecal samples determining their inhibitory activity against intestinal maltase, sucrase, lactase and amylase. Lactobacillus reference strains (Ref1–7), a Gram positive control (Ctrl1) and two Gram negative controls (Ctrl2–3), were also analysed to compare activity.Results
Faecal isolates were identified by DNA sequencing, with the majority identified as unique strains of Lactobacillus plantarum. Some strains (L. plantarum, L. fermentum, L. casei and L. rhamnosus) had potent and broad spectrum inhibitory activities (up to 89 %; p < 0.001; 500 mg/ml wet weight) comparable to acarbose (up to 88 %; p < 0.001; 30 mg/ml). Inhibitory activity was concentration-dependent and was freely available in the supernatant, and was not present in other bacterial genera (Bifidobacterium bifidum and Escherichia coli or Salmonella typhimurium). Interestingly, the potency and spectrum of inhibitory activity across strains of a single species (L. plantarum) differed substantially. Some Lactobacillus extracts had broader spectrum activities than acarbose, effectively inhibiting beta-glucosidase activity (lactase) as well as alpha-glucosidase activities (maltase, sucrase and amylase). Anti-diabetic potential was indicated by the fact that oral gavage with a L. rhamnosus extract (1 g/kg) was able to reduce glucose excursions (Area under curve; 22 %; p < 0.05) in rats during a carbohydrate challenge (starch; 2 g/kg).Conclusion
These results definitively demonstrate that Lactobacillus strains present in the human gut have alpha- and beta-glucosidase inhibitory activities and can reduce blood glucose responses in vivo. Although the potential use of LAB such as Lactobacillus as a dietary supplement, medicinal food or biotherapeutic for diabetes is uncertain, such an approach might offer advantages over drug therapies in terms of broader spectrum activities and fewer unpleasant side effects. Further characterisation of this bioactivity is warranted, and chronic studies should be undertaken in appropriate animal models or diabetic subjects. 相似文献988.
Harsh Chauhan Anuj Kuldipkumar Timothy Barder Ales Medek Chong-Hui Gu Eman Atef 《Pharmaceutical research》2014,31(2):500-515
Purpose
To correlate the polymer’s degree of precipitation inhibition of indomethacin in solution to the amorphous stabilization in solid state.Methods
Precipitation of indomethacin (IMC) in presence of polymers was continuously monitored by a UV spectrophotometer. Precipitates were characterized by PXRD, IR and SEM. Solid dispersions with different polymer to drug ratios were prepared using solvent evaporation. Crystallization of the solid dispersion was monitored using PXRD. Modulated differential scanning calorimetry (MDSC), IR, Raman and solid state NMR were used to explore the possible interactions between IMC and polymers.Results
PVP K90, HPMC and Eudragit E100 showed precipitation inhibitory effects in solution whereas Eudragit L100, Eudragit S100 and PEG 8000 showed no effect on IMC precipitation. The rank order of precipitation inhibitory effect on IMC was found to be PVP K90?>?Eudragit E100?>?HPMC. In the solid state, polymers showing precipitation inhibitory effect also exhibited amorphous stabilization of IMC with the same rank order of effectiveness. IR, Raman and solid state NMR studies showed that rank order of crystallization inhibition correlates with strength of molecular interaction between IMC and polymers.Conclusions
Correlation is observed in the polymers ability to inhibit precipitation in solution and amorphous stabilization in the solid state for IMC and can be explained by the strength of drug polymer interactions. 相似文献989.
Alsina M; Boyce B; Devlin RD; Anderson JL; Craig F; Mundy GR; Roodman GD 《Blood》1996,87(4):1495-1501
Osteolytic bone destruction and its complications, bone pain, pathologic fractures, and hypercalcemia, are a major source of morbidity and mortality in patients with multiple myeloma. The bone destruction in multiple myeloma is due to increased osteoclast (OCL) activity and decreased bone formation in areas of bone adjacent to myeloma cells. The mechanisms underlying osteolysis in multiple myeloma in vivo are unclear. We used a human plasma cell leukemia cell line, ARH-77, that has disseminated growth in mice with severe combined immunodeficiency (SCID) and expresses IgG kappa, as a model for human multiple myeloma, SCID mice were irradiated with 400 rads and mice were injected either with 10(6) ARH-77 cells intravenously (ARH-77 mice) or vehicle 24 hours after irradiation. Development of bone disease was assessed by blood ionized calcium levels, x-rays, and histology. All ARH-77, but none of control mice that survived irradiation, developed hind limb paralysis 28 to 35 days after injection and developed hypercalcemia (1.35 to 1.46 mmol/L) a mean of 5 days after becoming paraplegic. Lytic bone lesions were detected using x-rays in all the hypercalcemic mice examined. No lytic lesions or hypercalcemia developed in the controls. Controls or ARH-77 mice, after developing hypercalcemia, were then killed and bone marrow plasma from the long bones were obtained, concentrated, and assayed for bone-resorbing activity. Bone marrow plasma from ARH-77 mice induced significant bone resorption in the fetal rat long bone resorption assay when compared with controls (percentage of total 45Ca released = 35% +/- 4% v 11% +/- 1%). Histologic examination of tissues from the ARH-77 mice showed infiltration of myeloma cells in the liver and spleen and marked infiltration in vertebrae and long bones, with loss of bony trabeculae and increased OCL numbers. Interestingly, cultures of ARH-77 mouse bone marrow for early OCL precursors (colony-forming unit-granulocyte- macrophage [CFU-GM]) showed a threefold increase in CFU-GM from ARH-77 marrow versus controls (185 +/- 32 v 40 +/- 3 per 2 x 10(5) cell plated). Bone-resorbing human and murine cytokines such as interleukin- 6 (IL-6), IL-1 alpha or beta, TGF-alpha, lymphotoxin, and TNF alpha were not significantly increased in ARH-77 mouse sera or marrow plasma, compared with control mice, although ARH-77 cells produce IL-6 and lymphotoxin in vitro. Conditioned media from ARH-77 cells induced significant bone resorption in the fetal rat long bone resorption assay when compared with untreated media (percentage of total 45Ca released = 22% +/- 2% v 11% +/- 1%). This effect was not blocked by anti-IL-6 or antilymphotoxin (percentage of total 45Ca released = 19% +/- 1% and 22% +/- 1%, respectively). Thus, we have developed a model of human multiple myeloma bone disease that should be very useful to dissect the pathogenesis of the bone destruction in multiple myeloma. 相似文献
990.
An indirect immunofluorescence assay was used to quantitate TdT- containing (TdT+) cells in the mononuclear leukocyte fraction of peripheral blood from normal subjects and patients with acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LL). In normal children (10) and adults (10), 0.036% +/- 0.014% (mean +/- SD) and 0.030% +/- 0.015% TdT+ cells were found. In peripheral bloods from 10 children receiving chemotherapy for tumors other than ALL or LL, 0.040% +/- 0.039% TdT+ cells were found. Serial determinations were performed on 15 patients with ALL or LL who were in clinical remission. Eight of these patients remained in continuous remission and always had fewer than 0.11% TdT+ cells in their peripheral blood. Three patients who developed systemic relapse were found to have progressively rising numbers of TdT+ cells in their peripheral blood prior to clinical evidence of relapse. All 3 of these patients had greater than 0.1% TdT+ cells in their peripheral blood from 3 to 8 wk prior to clinical relapse. In 3 other patients, localized extramedullary relapse developed, but no trend was found on serial TdT determinations. Thus, the indirect immunofluorescence assay for TdT detects a small population of cells in normal peripheral blood. In patients with ALL, progressive increases above this normal level were associated with subsequent bone marrow relapse. 相似文献