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Biomedical subjects

N Rao

Publications and source records attributed to N Rao.

At least 37 records · Page 2Linked to original sources
PubMed2000

The relative rapidity of recanalization induced by recombinant tissue-type plasminogen activator (r-tPA) and TNK-tPA, assessed with enzymatic methods.

BACKGROUND: Comparison of different plasminogen activators is difficult because conventional endpoints such as mortality are relatively insensitive to potential differences in efficacy with respect to rapidity of recanalization of infarct-related arteries. METHODS: This study was performed to determine whether valid comparisons could be made by means of biochemical endpoints that have been demonstrated previously to permit estimation of the time of opening of an infarct-related artery in experimental animals and in patients. The method is based on time-dependent interconversion of isoforms of creatine kinase mediated by carboxypeptidase N, an enzyme present in excess in circulating blood. A small subset of 39 patients studied in the ASsessment of the Safety and Efficacy of a New Thrombolytic agent (ASSENT-2) trial were evaluated to determine the feasibility of using the creatine kinase isoform method for comparison of two tissue-type plasminogen activators (tPA), recombinant tPA (r-tPA) and TNK-tPA. RESULTS: Early recanalization (within 40 min of the onset of treatment with the plasminogen activator) occurred in 56% of patients treated with r-tPA and 76% of those treated with TNK-tPA. CONCLUSIONS: Differences in the efficacy of plasminogen activators with respect to rapidity of recanalization appear to be readily detectable by means of assaying creatine kinase isoforms in serially acquired blood samples under conditions that permit widespread application of the approach developed.

Biomarkers↗
PubMed1999

Molecular characterization of a third member of the guanylyl cyclase-activating protein subfamily.

The mammalian retina contains at least two guanylyl cyclases (GC1 and GC2) and two guanylyl cyclase-activating proteins (GCAP1 and GCAP2). Here we present evidence of the presence of a new photoreceptor-specific GCAP, termed GCAP3, which is closely related to GCAP1. The sequence similarity of GCAP3 with GCAP1 and GCAP2 is 57 and 49%, respectively. Recombinant GCAP3 and GCAP2 stimulate GC1 and GC2 in low [Ca2+]free and inhibit GCs when [Ca2+]free is elevated, unlike GCAP1, which only stimulates GC1. GCAP3 is encoded by a distinct gene present in other mammalian species but could not be detected by genomic Southern blotting in rodents, amphibians, and lower vertebrates. The intron/exon arrangement of the GCAP3 gene is identical to that of the other GCAP genes. While the GCAP1 and GCAP2 genes are arranged in a tail-to-tail array on chromosome 6p in human, the GCAP3 gene is located on 3q13.1, suggesting an ancestral gene duplication/translocation event. The identification of multiple Ca2+-binding proteins that interact with GC is suggestive of complex regulatory mechanisms for photoreceptor GC.

Amino Acid Sequence↗
PubMed1999

Positional isomers of acetaminophen differentially induce proliferation of cultured breast cancer cells.

This study demonstrates that acetaminophen (p-acetamidophenol) stimulates proliferation of estrogen-responsive cultured breast cancer cells and assesses if the proliferative activity of p-acetamidophenol is influenced by the -OH moiety position on the benzene ring. The effects of p-, m-, and o-acetamidophenol on cell number and on percentage cells in S phase of the cell cycle were determined for two estrogen receptor positive, human breast cancer cell lines, T47D and MCF7. Therapeutic concentrations of p-acetamidophenol (0.1 mM) significantly increased breast cancer cell proliferation. The relative order of potency of isomers in stimulating proliferation in both cell types was p- > m- > o-acetamidophenol, indicating the -OH position on the benzene ring influences the proliferation output in cultured breast cancer cells.

Acetaminophen↗
PubMed1999

The systemic safety of fexofenadine HCl.

Fexofenadine is a highly specific, H1-receptor antagonist with a safety profile similar to placebo. In placebo-controlled trials of seasonal allergic rhinitis (SAR) and chronic idiopathic urticaria (CIU), the type and incidence of adverse events were comparable in fexofenadine and placebo recipients. Fexofenadine does not impair performance in tests of driving or psychomotor performance and has been shown to improve quality of life in patients with SAR. Fexofenadine has a high margin of safety and is also well tolerated in subjects with renal or hepatic impairment, in children and the elderly. No clinically significant drug interactions have been identified. Fexofenadine is not associated with cardiotoxicity. Unlike some other antihistamines, such as loratidine or cetirizine [1, 2], fexofenadine is truly non-sedating, showing no dose-related increase in sedation, even at high doses [3, 4]. Fexofenadine is formulated and marketed as the hydrochloride salt. The recommended dose of fexofenadine HC1 is 120 mg daily for SAR (either as 120 mg once daily or 60 mg twice daily) or 180 mg once daily for CIU.

Aged↗
PubMed1999

Effects of an entertainment-education radio soap opera on family planning behavior in Tanzania.

An entertainment-education radio soap opera introduced in Tanzania in 1993 was evaluated by means of a field experimental design in which the radio program was broadcast by seven mainland stations of Radio Tanzania. An eighth station broadcast alternative programming from 1993 to 1995, its listenership serving as a comparison area in which contemporaneous changes in family planning adoption were measured. The soap opera was subsequently broadcast nationwide from 1995 to 1997. Data about the effects of the radio soap opera were gathered in five annual surveys of about 2,750 households in the comparison and the treatment areas and from a sample of new family planning adopters in 79 health clinics. The soap opera had strong behavioral effects on family planning adoption; it increased listeners' self-efficacy regarding family planning adoption and influenced listeners to talk with their spouses and peers about contraception.

Adult↗
PubMed1998

Cbl-mediated negative regulation of the Syk tyrosine kinase. A critical role for Cbl phosphotyrosine-binding domain binding to Syk phosphotyrosine 323.

The proto-oncogene product Cbl has emerged as a potential negative regulator of the Syk tyrosine kinase; however, the nature of physical interactions between Cbl and Syk that are critical for this negative regulation remains unclear. Here we show that the phosphotyrosine-binding (PTB) domain within the N-terminal transforming region of Cbl (Cbl-N) binds to phosphorylated Tyr323 in the linker region between the Src homology 2 and kinase domains of Syk, confirming recent results by another laboratory using the yeast two-hybrid approach (Deckert, M., Elly, C., Altman, A., and Liu, Y. C. (1998) J. Biol. Chem. 273, 8867-8874). A PTB domain-inactivating point mutation (G306E), corresponding to a loss-of-function mutation in the Caenorhabditis elegans Cbl homologue SLI-1, severely compromised Cbl-N/Syk binding in vitro and Cbl/Syk association in transfected COS-7 cells. Using heterologous expression in COS-7 cells, we investigated the role of Cbl PTB domain binding to Syk Tyr323 in the negative regulation of Syk. Co-expression of Cbl with Syk in COS-7 cells led to a dose-dependent decrease in the autophosphorylated pool of Syk and in phosphorylation of an in vivo substrate, CD8-zeta. Unexpectedly, these effects were largely due to the loss of Syk protein. Both the decrease in Syk and CD8-zeta phosphorylation and reduction in Syk protein levels were blocked by either G306E mutation in Cbl or by Y323F mutation in Syk. These results demonstrate a critical role for the Cbl PTB domain in the recruitment of Cbl to Syk and in Cbl-mediated negative regulation of Syk.

Binding Sites↗
PubMed1998

Fine localization of the CMT4A locus using a PAC contig and haplotype analysis.

Charcot-Marie-Tooth disease type 4A (CMT4A) is a severe, autosomal recessive peripheral neuropathy linked to chromosome 8q13-q21. We have previously constructed a YAC contig across the CMT4A region and narrowed the disease-flanking interval to approximately three megabases. Subsequently, we constructed a PAC/BAC contig made of 44 clones and mapped 44 new and 30 previous STSs, ESTs, and polymorphic makers to the region. Using 13 polymorphic markers, we have now identified an ancestral haplotype segregating in three families, indicating a common founder mutation. Two ancestral recombination events in this haplotype significantly reduce the minimal candidate region to a minimal trailing path of five PAC/BAC clones, which will now allow direct investigation of candidate genes for CMT4A.

Alleles↗
PubMed1998

Sarcoidosis and central serous retinopathy: a dangerous combination.

Central serous retinopathy, a disorder of healthy young men, has also been reported to occur in patients with collagen vascular disease. This is the first report discussing the occurrence of central serous retinopathy in patients with sarcoidosis. It is critical to recognize the entity because corticosteroids, used in treating sarcoidosis, can have a disastrous effect on central serous retinopathy.

Adult↗
PubMed1997

Cytomegalovirus retinitis after initiation of highly active antiretroviral therapy.

BACKGROUND: In previous natural history studies and clinical trials, AIDS-related cytomegalovirus (CMV) retinitis has occurred primarily in patients with absolute CD4 counts of 50 cells/microL or less (0.05 x 10(9)/L) at the time of diagnosis. METHODS: We report five patients identified from our clinical practices who were diagnosed with CMV retinitis while their CD4 counts were above 195 cells/microL. We also analysed, based on CD4 counts, 76 AIDS patients with newly diagnosed CMV retinitis whose CD4 lymphocyte enumerations were done in laboratories that maintained certification in a common external quality control programme. FINDINGS: 5-24 weeks before retinitis was diagnosed, all five patients had had absolute CD4 lymphocyte counts of less than 85 cells/microL, and 4-7 weeks before diagnosis, all five patients had started taking highly active antiretroviral treatment (HAART) regimens. Only one (4%) of 27 patients enrolled in the trial between July, 1995, and February, 1996, had an absolute CD4 count of more than 50 cells/microL, and none of 27 had an absolute CD4 count of more than 100/microL on entry to the trial. However, from March, 1996 (when indinavir and ritonavir were approved by the FDA for marketing in the USA), to August, 1996, 14 (29%) of 49 patients had CD4 counts of more than 50/microL and seven (14%) of 49 had a CD4 count of more than 100 cells/microL on entry. INTERPRETATION: These findings suggest that the early immunological effects of HAART may not provide sufficient protection to prevent CMV retinitis in patients who have very low CD4 counts when therapy is started. Clinicians should note that CMV retinitis may now occur in patients who have CD4 counts of more than 100 cells/microL.

AIDS-Related Opportunistic Infections↗
PubMed1997

Vascular endothelial growth factor is a potent angiogenic factor in AIDS-associated Kaposi's sarcoma-derived spindle cells.

Angiogenesis is one of the most important features of AIDS-associated Kaposi's sarcoma (AIDS-KS). Our studies suggested that spindle-shaped AIDS-KS cells from various AIDS-KS lesions play important roles in the development of KS lesions. Basic fibroblast growth factor (bFGF) has been reported to be a predominant angiogenic factor expressed in AIDS-KS cells. However, our data from ELISA revealed the presence of the vascular endothelial growth factor (VEGF) molecule in large quantities in AIDS-KS cell-derived conditioned medium (AIDS-KS-CM) (12.1-21.4 ng/ml). In contrast, small amounts of bFGF were detected in AIDS-KS-CM (76-245 pg/ml). The combination of anti-VEGF and anti-bFGF IgGs completely inhibited endothelial cell growth-promoting activities in AIDS-KS-CM, while activities partially remained in the presence of anti-bFGF IgG or anti-VEGF IgG alone. VEGF and bFGF in AIDS-KS-CM were distinguished by heparin-affinity chromatography. Furthermore, the combination of VEGF and bFGF synergistically augmented the growth of endothelial cells. Both VEGF and bFGF revealed an angiogenic property that was inhibited by specific Abs, when applied to the rabbit cornea and chicken chorioallantoic membrane. On Western blots, anti-VEGF IgG gave two major bands of 22 and 24 kDa, similar to those of recombinant VEGF165. As detected on Northern blots, AIDS-KS cells expressed major 3.9-kb VEGF-specific mRNA. Thus, VEGF, in concert with bFGF, may play a crucial role in the angiogenesis of AIDS-KS lesions.

Animals↗
PubMed1997

Comparative absorption of bismuth in Sprague-Dawley rats following oral administration of preparations containing bismuth sucrose octasulfate, bismuth subsalicylate, and bismuth subcitrate.

The absorption of bismuth from De-Nol (bismuth subcitrate, DN), Pepto-Bismol (bismuth subsalicylate, PB) and bismuth sucrose octasulfate (BISOS) was examined in male Sprague-Dawley rats after a single oral dose of each compound (60mg bismuth). Bismuth was analysed in blood, urine, kidney, brain, liver, and lung using graphite furnace atomic absorption spectrophotometry. Bismuth Cmax averaged 18.4 +/- 11.6 ng mL(-1) for BISOS, 292 +/- 130 ng mL(-1) for DN, and 21.5 +/- 9.63 ng mL(-1 ) for PB. Cmax was significantly lower for BISOS compared to DN (p<0.05) but not significantly different for BISOS compared to PB (p > 0.05). Bismuth AUC was 1356 +/- 474 ng h(-1) mL (-1) for BISOS, 2129 +/- 452 ng h(-l) mL(-1) for DN, and 1824 +/- 919 ng h(-1) for PB, which indicated a lower extent of absorption from BISOS compared to DN. Kidney, liver, and lung levels of bismuth were also significantly lower for BISOS compared to DN (p < 0.05). Bismuth urinary excretion was significantly lower for BISOS (0.04 +/- 0.02%) compared to DN (0.27 +/- 0.15%) but not significantly different compared to PB (0.07 +/- 0.03%). These data suggest that the absorption of bismuth following oral administration of bismuth sucrose octasulfate is significantly lower than that from De-Nol and similar to that from Pepto-Bismo.

Administration, Oral↗
PubMed1997

Mass balance of 14C-bismuth sucrose octasulfate in Sprague-Dawley rats: evidence for dissociation of bismuth from sucrose octasulfate.

The mass balance of 14C bismuth sucrose octasulfate (BISOS) was investigated in eight male Sprague-Dawley rats after single oral doses of 1.0 g kg-1. Bismuth and radioactivity were monitored in blood, urine, and feces for up to 144 h post-dose, while kidneys, brain, liver, and lungs were assayed for bismuth at 144 h post-dose. In a separate experiment, bismuth was monitored in bile of bile-duct-cannulated animals for 48 h post-dose. Fecal excretion of bismuth averaged 95.8 +/- 5.30% bismuth dose, while 99.2 +/- 3.63% of the radiolabel was excreted in feces. Urinary excretion of bismuth averaged 0.051 +/- 0.028% bismuth dose, and 1.83 +/- 1.08% radioactive dose. Biliary excretion of bismuth averaged 0.0003 +/- 0.0006% bismuth dose, and 0.026 +/- 0.030% radiolabeled dose. An average 0.005 +/- 0.002% of the bismuth dose was present in kidney, liver, and lung. Bismuth levels in brain were below quantifiable limits. Though BISOS contains 57.3% by weight of bismuth, peak blood concentrations of bismuth were three orders of magnitude lower than for BISOS equivalents (Cmax for BISOS averaged 110 +/- 55.4 micrograms eq mL-1, while for bismuth it was 26.1 +/- 10.3 ng mL-1). This data indicates that bismuth dissociates from sucrose octasulfate, probably during the absorption phase, and exhibits differential pharmacokinetic characteristics from sucrose octasulfate. The low biliary and urinary excretion of both bismuth and BISOS equivalents is indicative of low systemic absorption. Greater than 96% recovery in feces, bile, and urine indicates that mass balance was achieved following oral administration.

Absorption↗
PubMed1997

Leukocyte phenotypic changes in an in vitro model of ABO hemolytic transfusion reaction.

BACKGROUND: ABO antigen-antibody interaction in the presence of peripheral blood leukocytes (white cells) results in the production of a variety of proinflammatory cytokines. However, although tumor necrosis factor alpha has been shown to be derived at least primarily from monocytes, the range of cells activated by this process has not previously been reported. Therefore, changes in mononuclear cell surface antigen expression were studied, to determine which subsets of white cells appeared to be activated in the setting of ABO incompatibility. STUDY DESIGN AND METHODS: Group O peripheral blood mononuclear cells (PBMCs) were incubated in autologous plasma with group A or O red cells (RBCs) for up to 24 hours. White cell expression of activation and adhesion markers was measured at 2 and 24 hours by flow cytometry, using direct or indirect fluorescein or phycoerythrin labeling. RESULTS: Expression of lymphocyte activation markers CD25, CDw108, and CD109 was equivalent when PBMCs incubated with group A and O RBCs were compared. However, after 2 hours, mean fluorescence of CD14 on PBMCs incubated with group A RBCs was 65 percent of that on PBMCs incubated with group O RBCs and remained similarly decreased at 24 hours. CD44 expression was upregulated on PBMCs exposed to both group A and O RBCs, but it was increased significantly more on monocytes exposed to group A RBCs. The ability to bind hyaluronic acid was induced in approximately 42 percent of CD14+ monocytes exposed to group A RBCs but in no cells exposed to group O RBCs. CONCLUSION: Downregulation of CD14 and increased binding of hyaluronic acid reflects monocyte activation in this model. No evidence of lymphocyte activation was found, supporting the hypothesis that ABO transfusion reactions primarily activate monocytes.

ABO Blood-Group System↗
PubMed1997

A basic motif in the N-terminal region of RAG1 enhances V(D)J recombination activity.

The variable portions of antigen receptor genes are assembled from component gene segments by a site-specific recombination reaction known as V(D)J recombination. The RAG1 and RAG2 proteins are the critical lymphoid cell-specific components of the recombination enzymatic machinery and are responsible for site-specific DNA recognition and cleavage. Previous studies had defined a minimal, recombinationally active core region of murine RAG1 consisting of amino acids 384 to 1008 of the 1,040-residue RAG1 protein. No recombination function has heretofore been ascribed to any portion of the 383-amino-acid N-terminal region that is missing from the core, but it seems likely to be of functional significance, based on its evolutionary conservation. Using extrachromosomal recombination substrates, we demonstrate here that the N-terminal region enhances the recombination activity of RAG1 by up to an order of magnitude in a variety of cell lines. Deletion analysis localized a region of the N terminus critical for this effect to amino acids 216 to 238, and further mutagenesis demonstrated that a small basic amino acid motif (BIIa) in this region is essential for enhancing the activity of RAG1. Despite the fact that BIIa is important for the interaction of RAG1 with the nuclear localization factor Srp-1, it does not appear to enhance recombination by facilitating nuclear transport of RAG1. A variety of models for how this region stimulates the recombination activity of RAG1 are considered.

Amino Acid Sequence↗
PubMed1997

Transthoracic needle biopsy of small pulmonary nodules.

PURPOSE: To evaluate the diagnostic accuracy, complications, and usefulness of transthoracic needle biopsy of small pulmonary nodules. MATERIALS AND METHODS: Between January 1993 and January 1995, 302 patients underwent transthoracic needle biopsy of pulmonary lesions. Sixty-four lesions (in 62 patients) represented small nodules, defined as lesions of 15 mm or less maximum diameter. A total of 75 biopsies were performed in the 64 lesions. Approximately 90% of the biopsies were performed with computed tomographic guidance. RESULTS: There were 21 benign lesions and 43 cancers (36 primary, seven metastatic). Transthoracic needle biopsy findings were positive for cancer in 40 cases. In all three false-negative lesions, only one biopsy was performed. There were 21 true-negative results and no false-positive results. Positive and negative predictive values were 100% and 88%, respectively. Pneumothorax occurred in 20 (27%) of 75 biopsies, but chest tube placement was necessary in only three cases (4%). Surgery or thoracoscopy was avoided in 31 patients: 17 of 20 patients with benign disease, seven patients with metastatic disease, and seven patients with inoperable lung cancer. CONCLUSION: Transthoracic needle biopsy of small pulmonary nodules can produce diagnostic yields comparable with published results of transthoracic needle biopsy of larger lesions.

Adult↗