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111.
Seventy-five unrelated hemophilia A patients from India were analyzed for factor VIII gene defects. Intron 22 inversion was identified in 22 patients and intron 1 inversion in 2 patients. In the remaining 51 patients without inversions screening the FVIII gene by denaturing high performance liquid chromatography (DHPLC) revealed 42 different mutations in 44 unrelated subjects. These included 14 missense, 7 nonsense, 9 splice site, 8 deletional, 3 insertional mutations and one indel mutation. Of these, 32 were novel gene alterations. The hotspots included intron 22 inversion, CpG and adenine runs. 相似文献
112.
Thirty-seven young patients (less than 42 years of age) presenting with sudden onset of idiopathic nonembolic cerebrovascular disease were evaluated for underlying prothrombotic factors. Activated protein C resistance (APC-R) was measured by Dahlback's method and the modified method using factor V-deficient plasma. Activities of antithrombin (AT) III, protein C and S were measured. Anticardiolipin antibody was estimated by ELISA and lupus anticoagulant by kaolin clotting tests. APC-R was the most common defect (21.62%) followed by AT III deficiency and presence of anticardiolipin antibodies (5.6% each). The latter two were present together in one case. It is thus concluded that APC-R is the most common defect underlying idiopathic nonembolic cerebrovascular infarction in young individuals. 相似文献
113.
Hemophilia A: role of FVIIIC/vWF Ag in assisting linkage analysis for carrier detection. 总被引:2,自引:0,他引:2
R P H Ahmed P K Gupta M Kannan K Suresh R Kashyap V P Choudhry R Saxena 《Clinical and applied thrombosis/hemostasis》2004,10(2):127-131
Carrier detection for hemophilia A was carried out in 52 females from 30 families presenting to the Haematology Department AIIMS, using linkage analysis and factor VIIIC (FVIIIC)-von Willebrand factor (vWF) antigen assay. The allelic frequency for the marker Bcl 1 and Xba 1 was 0.58 and 0.54, respectively, for the positive alleles and 0.42 and 0.46, respectively, for the negative alleles. The heterozygosity frequency of Bcl I and Xba 1 was 0.65 and 0.55, respectively. Of the 52 females, 30 were mothers of hemophilic patients and 22 were sisters of hemophilic patients. Of the 30 mothers, positive family history was present in 14. In these patients, the defective X chromosome was tracked in 10, and in four the defective X chromosome could not be tracked because the mothers were homozygous for the marker used. Of the 16 mothers without a family history of disease, three were observed to be carriers based on linkage analysis and reduced factor VIII levels in mother/sister. Possible defective X chromosome was tracked in 11 mothers and five were noninformative because they did not show heterozygosity for the markers used. Using linkage analysis, nine of the 22 sisters were found to be definite carriers, 10 noncarriers, and three were noninformative. It is thus concluded that using Bcl 1 and Xba 1 linkage analysis, carrier status can be definitely ascertained in 50% females and this level of information can be increased to 61.5% by measuring FVIIIC/vWF antigen levels in them. 相似文献
114.
Mamtesh Gupta Rajnish Juneja Anita Saxena 《Catheterization and cardiovascular interventions》2003,58(4):545-547
Percutaneous closure of ventricular septal defect and pulmonary valvuloplasty appears to be an attractive modality when compared to surgical treatment for both lesions. We report successful transcatheter closure of muscular ventricular septal defect with pulmonary valve balloon dilation performed simultaneously in a 27-year-old woman. Technical considerations in such a setting are being discussed. 相似文献
115.
Rubha Saxena 《Drug delivery》2015,22(2):156-167
AbstractElastin-like polypeptides (ELPs) are large molecular weight biopolymers. They have been widely studied as macromolecular carriers for targeted delivery of drugs. The aim of the present article is to review the available information on ELPs (including our recent investigations), their properties, drug delivery applications to tumor sites and future perspectives. This review also provides information on the use of short synthetic ELPs for making ELP-drug conjugates, for targeted delivery of anticancer drugs. In the present review we also focus on the point that short ELPs can also be used for targeting anticancer drugs to tumor sites as they behave similar to long ELPs regarding their capacity to undergo inverse temperature transition (ITT) behavior. 相似文献
116.
117.
Schuijt MP Tom B de Vries R Saxena PR Sluiter W van Kats JP Danser AH 《Journal of hypertension》2003,21(12):2335-2344
OBJECTIVE: To investigate whether superoxide mediates angiotensin (Ang) II-induced vasoconstriction. METHODS: Human coronary arteries (HCAs), porcine femoral arteries (PFA) and porcine coronary arteries (PCAs) were mounted in organ baths and concentration-response curves to Ang II, the nitric oxide (NO) donor S-nitroso-N-acetylpenicillamine (SNAP) and the NAD(P)H oxidase substrate NADH were constructed in the absence and presence of superoxide inhibiting and activating drugs. Extracellular superoxide was measured using cytochrome c reduction. RESULTS: Ang II constricted both HCAs and PFAs. In HCAs, the NAD(P)H inhibitors diphenyleneiodonium (DPI) and apocynin, and the xanthine oxidase (XO) inhibitor allopurinol, but not the superoxide dismutase (SOD) mimetic tempol or the SOD inhibitor diethyldithiocarbamate (DETCA), reduced this constriction. Catalase potentiated Ang II in HCAs, indicating a vasodilator role for H2O2. DPI, tempol and SOD did not affect Ang II in PFAs. DPI, apocynin and allopurinol relaxed preconstricted HCAs. Although the relaxant effects of the NO donor SNAP in PCAs was reduced by DETCA, indicating that superoxide-induced constrictions depend on NO inactivation, the apocynin-induced relaxations were NO independent. Moreover, NADH relaxed all vessels, and this effect was blocked by KCl but not DPI or NO removal. Xanthine plus XO also relaxed HCAs and PCAs. Incubation of human or porcine arteries with Ang II or NADH did not result in detectable increases of extracellular superoxide within 1 h. CONCLUSIONS: Acute vasoconstriction by Ang II is not mediated via superoxide generated through NAD(P)H oxidase and/or XO activation. Such activation, if occurring, rather results in the generation of the vasodilator H2O2. 相似文献
118.
Suppression of apoptosis in hematopoietic factor-dependent progenitor cell lines by expression of the FAC gene 总被引:2,自引:5,他引:2
Fanconi anemia (FA) is a genetically heterogeneous, inherited blood disorder characterized by bone marrow failure, congenital malformations, and a predisposition to leukemias. Because FA cells are hypersensitive to DNA cross-linking agents and have chromosomal instability, FA has been viewed as a disorder of DNA repair. However, the exact cellular defect in FA cells has not been identified. Sequence analysis of the gene defective in group C patients (FAC) has shown no significant homologies to other known genes. The FAC protein has been localized to the cytoplasm, indicating that FAC may either play an indirect role in DNA repair or is involved in a different cellular pathway. Recent evidence has indicated that FA cells may be predisposed to apoptosis, especially after treatment with DNA cross-linking agents. The demonstration that genes can suppress apoptosis has been accomplished by overexpression of such genes in growth factor-dependent cell lines that die by apoptosis after factor withdrawal. Using retroviral-mediated gene transfer, we present evidence that expression of FAC in the hematopoietic factor-dependent progenitor cell lines 32D and MO7e can suppress apoptosis induced by growth factor withdrawal. Flow cytometry and morphologic analysis of propidium iodide stained cells showed significantly lower levels of apoptosis in FAC-retroviral transduced cells after growth factor deprivation. Expression of FAC in both cell lines promoted increased viability rather than proliferation, which is consistent with other apoptosis-inhibiting genes such as Bcl- 2. These findings imply that FAC may act as a mediator of an apoptotic pathway initiated by growth factor withdrawal. Furthermore, the congenital malformations and hematologic abnormalities characterizing FA may be related to an increased predisposition of FA progenitor cells to undergo apoptosis, particularly in the absence of extracellular signals. 相似文献
119.
Direct evidence for modified solvent structure within the hydration shell of a hydrophobic amino acid. 总被引:2,自引:0,他引:2
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A Pertsemlidis A M Saxena A K Soper T Head-Gordon R M Glaeser 《Proceedings of the National Academy of Sciences of the United States of America》1996,93(20):10769-10774
Neutron scattering experiments are used to determine scattering profiles for aqueous solutions of hydrophobic and hydrophilic amino acid analogs. Solutions of hydrophobic solutes show a shift in the main diffraction peak to smaller angle as compared with pure water, whereas solutions of hydrophilic solutes do not. The same difference for solutions of hydrophobic and hydrophilic side chains is also predicted by molecular dynamics simulations. The neutron scattering curves of aqueous solutions of hydrophobic amino acids at room temperature are qualitatively similar to differences between the liquid molecular structure functions measured for ambient and supercooled water. The nonpolar solute-induced expansion of water structure reported here is also complementary to recent neutron experiments where compression of aqueous solvent structure has been observed at high salt concentration. 相似文献
120.
Factors that affect human hemopoiesis are produced by T-cell growth factor dependent and independent cultured T-cell leukemia-lymphoma cells 总被引:3,自引:0,他引:3
Some laboratory results and clinical situations suggest that human T cells may be important in the regulation of growth of hematopoietic cells. Since the discovery of T-cell growth factor (TCGF), systems are now available for the long-term specific in vitro propagation of mature normal or neoplastic human T cells, providing an opportunity to study the influence of T cells on hematopoiesis. Recently, 24 cell lines from patients with cutaneous T-cell lymphoma (CTCL) and T-cell acute lymphoblastic leukemia (T-ALL) were grown with TCGF and then assessed for release of humoral factors that affect hematopoiesis. Conditioned media (CM) from these cell lines were tested for erythroid burst- promoting activity (BPA) and granulocyte colony-stimulating activity (CSA). BPA was detected in CM from 3/6 cultures of T-ALL patients and 4/6 CTCL cultures. CSA was found in the CM from 6/8 cultures of T-ALL patients, 7/12 CTCL cultures, and 3/4 CTCL cell lines that become independent of exogenous TCGF for growth. The CSA from several of the neoplastic T-cell cultures stimulated high levels of eosinophil colonies, a possible source of the eosinophilia seen in these patients. The ability of continuously proliferating human T lymphocytes, which retain functional specificity and responsiveness to normal humoral regulation, to produce factors that directly or indirectly stimulate myeloid and erythroid colony formation lends further credence to the role of T lymphocytes in regulating hematopoiesis. 相似文献