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Biomedical subjects

A Bansal

Publications and source records attributed to A Bansal.

At least 73 records · Page 4Linked to original sources

Molecular basis for the resistance of influenza viruses to 4-guanidino-Neu5Ac2en.

We report the selection and characterization of influenza A/NWS-G70c and B/HK/8/73 (HG) viruses which are resistant to the potent influenza neuraminidase inhibitor, 4-guanidino-Neu5Ac2en. Viruses were selected which replicated in MDCK cells in the presence of 20 micrograms/ml inhibitor. The neuraminidase of resistant viruses was > 200-fold more resistant to 4-guanidino-Neu5Ac2en than was the neuraminidase of the parent viruses. Although amounts of neuraminidase protein were similar in resistant and parent viruses, the enzyme activity of the resistant neuraminidase heads was reduced by > 95% for the substrates used. Relative to parent viruses, the resistant viruses replicated to equal or greater titers in tissue culture and in embryonated chicken eggs. Sequence analysis revealed a single nucleotide mutation in the neuraminidase gene of each virus resulting in the change of the conserved Glu 119 (which lies in a pocket beneath the active site of the enzyme) to Gly thus eliminating an electrostatic interaction with the C-4 guanidinium moiety of the inhibitor. Mutations (Asn-->Ser) at amino acids 145 and 150 were also found in the hemagglutinin gene of the B/HK/8/73 (HG) virus resistant to 4-guanidino-Neu5Ac2en. No changes were found in the hemagglutinin gene of the resistant A/NWS-G70c virus.

Amino Acid Sequence↗

An investigation to determine whether clusters of cancer types exist in nine breast-ovary families.

Monte-Carlo simulations were carried out on nine BRCA1-linked families selected from the 1993 Breast Cancer Linkage Consortium. These families all displayed a prevalence of both breast and ovarian cancers, but little evidence was found to conclude that sufferers of either type formed clusters in particular branches of families. It was noted that the application of these methods to larger pedigrees with known probands would be useful in further clarifying the issue.

Age of Onset↗

Capsulotomy for phacoemulsification in hypermature cataracts.

We describe a modified surgical technique of anterior capsulotomy and phacoemulsification for use in hypermature cataracts. Surgical steps included inferior linear capsulotomy with aspiration of milky cortex, inflation of the capsular sac with viscoelastic, a reverse triangular anterior capsulotomy with Vannas scissors, and in-the-bag bimanual sculpting of the nucleus. An oval 5 mm x 6 mm posterior chamber intraocular lens was used with single horizontal or no-stitch wound closure. The technique was used successfully in 20 cases of hypermature cataract. The mean time required to perform phacoemulsification was 3.46 minutes (range 1.2 to 6.3 minutes), with a standard deviation of 1.29. Visual acuity on the first postoperative day ranged from 20/20 to 20/60 (median 20/40). At one week, the mean astigmatism was 1.01 diopters (range 0.25 to 2.75 diopters). The mean endothelial cell loss was 13% (range 3.6% to 26.0%). Based on our results, the modified phacoemulsification technique merits consideration for use in hypermature cataracts.

Adult↗

Serum-soluble CD23 in patients with endometriosis and the effect of treatment with danazol and leuprolide acetate depot injection.

Activated B cells have recently been shown to produce soluble CD23 from their membranes. The serum-soluble CD23 concentration in 21 patients with pelvic pain diagnosed as having endometriosis and confirmed by histology, and in 18 patients without pelvic pain, who had a normal pelvis during laparoscopic sterilization, was studied by chemiluminescent enzyme-linked immunosorbent assay. The endometriosis patients were randomized to 3 months of either danazol or leuprolide acetate injection. Serum was taken before and after 3 months of therapy. The serum-soluble CD23 concentration was significantly elevated in patients with endometriosis when compared with the controls (P < 0.0001). There was no correlation between soluble CD23 concentrations and the severity of endometriosis (r = 0.48, P > 0.05). The serum concentration of soluble CD23 decreased significantly on treatment with danazol but not leuprolide acetate (P < 0.05). We conclude that the elevation of soluble CD23 in patients with endometriosis suggests that there is activation of B cells, which respond to danazol but not leuprolide acetate injection.

B-Lymphocytes↗

Amino-aromatic interaction between histidine 197 of the neurokinin-1 receptor and CP 96345.

Substance P is a peptide neurotransmitter that binds to the neurokinin-1 receptor and is involved in pain transmission and neurogenic inflammation. Recently, a non-peptide substance P antagonist (CP 96345) has been shown to be effective in animal models of pain and inflammation. An understanding of the molecular interactions responsible for ligand binding will be critical for the development of more specific and selective antagonists for the neurokinin-1 receptor and for the discovery of new antagonists for related G-protein-coupled receptors. Here we report that histidine at position 197 in the fifth transmembrane helix of the human neurokinin-1 receptor binds specifically to CP 96345 but not to peptide agonists. Substitution of His 197 by different amino acids and analysis of structural analogues of antagonists suggest that His 197 is involved in an amino-aromatic interaction with the benzhydryl moiety of CP 96345.

Amino Acid Sequence↗

Circadian periodicity of urinary inhibitor of calcium oxalate crystallization in healthy Indians and renal stone formers.

The inhibitory activity (IA) of calcium oxalate crystallization was investigated in healthy Indians and renal stone formers. A marked circadian rhythm was observed in men and women of both groups. The rhythm pattern was similar on the basis of sex; however, it was different in stone formers as compared to normals. The acrophase for crystallization of calcium oxalate was observed, respectively, at 05.43 and 05.52 h in healthy men and women, and at 09.52 and 09.23 h in male and female renal stone formers. Moreover, the acrophase of percent inhibition by IA was observed at 17.44 and 17.52 h in healthy participants and at 21.52 and 21.27 h in male and female stone formers, respectively. Therefore, the acrophase suggests a highest risk of crystallization during the morning hours and a minimum one during the evening hours. The day-night rhythmic pattern of urinary calcium, magnesium and phosphorus is discussed in relation to the rhythm of IA.

Adolescent↗

Portal-vein obstruction in children leads to growth retardation.

The portal vein is the main source of blood and hepatotrophic factors to the liver. Partial portal-vein ligation in rats results in reduced growth compared with that in control rats. To investigate whether extrahepatic portal vein obstruction occurring in early childhood influences growth in humans, anthropometric and nutritional assessments were prospectively carried out in 61 patients with extrahepatic portal vein obstruction. Comparisons were made with 183 matched healthy controls using National Center of Health Statistics reference. Fifty-one percent of children with extrahepatic portal vein obstruction had stunted growth (height for age less than 90% of normal), compared with 16% of controls (p less than 0.01). Growth retardation was severe in patients with longer (greater than 5 yr) than with shorter (less than 2.5 yr) duration of clinical portal hypertension (height for age, 88.0 +/- 3.2 vs. 95.1 +/- 3.0; p less than 0.01). Little difference was seen in the energy intake (1,302 +/- 463 kcal/day vs. 1,335 +/- 449 kcal/day; p = not significant) and weight for height index (83.6 +/- 9.3 vs. 88.0 +/- 7.9; p = not significant) between extrahepatic portal vein obstruction patients and controls. This suggested that despite comparable nutrition, marked growth retardation occurred in extrahepatic portal vein obstruction patients. Incremental growth velocity was studied in 31 patients; in 24 (73%) the baseline Z score (-2.1 +/- 0.2) had decreased further (-2.4 +/- 0.2) at the end of follow-up (15.5 +/- 1.6 mo). Although the incremental height velocity was only 56% of the expected height, incremental weight gain was 98% of the expected weight for the attained height.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Soluble CD23 levels are elevated in the serum of patients with primary Sjögren's syndrome and systemic lupus erythematosus.

The low affinity IgE receptor Fc epsilon RII (CD23) is important in several aspects of T and B cell function. In this study serum levels of soluble CD23 (sCD23) were measured in three groups: 26 female patients with systemic lupus erythematosus (SLE), 21 females with primary Sjögren's syndrome (pSS) and 25 normal healthy females. The concentration of sCD23 was determined using an enhanced chemiluminescent sandwich ELISA developed in this laboratory. Increased levels of sCD23 were observed in pSS and in SLE patients compared with controls (median 23.0 versus 8.6, P less than 0.0002 and 18.1 versus 8.6, P less than 0.002 respectively). While the median level of sCD23 was found to be higher in pSS than in SLE the difference was not statistically significant. Patients with SLE and pSS on glucocorticoid treatment had significantly lower levels of sCD23 than patients not on this treatment (median 28.9 versus 14.4, P less than 0.05). Amongst the control patients sCD23 was inexplicably lower in the female members relative to the males (median 8.5 versus 12.3, P less than 0.05). Although serum IgG and IgA levels were significantly elevated in pSS and SLE patients relative to controls there was no direct correlation between sCD23 and the serum levels of these immunoglobulins. We conclude that B cell hyperactivity which occurs in both pSS and SLE is associated with raised levels of sCD23.

Adult↗

Characterization of the binding of a potent, selective, radioiodinated antagonist to the human neurokinin-1 receptor.

We have synthesized a potent, selective, radioiodinated antagonist of the human neurokinin-1 (NK1) receptor and have characterized its binding to the cloned receptor expressed in Chinese hamster ovary cells. (cis)-2-(Diphenylmethyl)-N-[(2-iodophenyl)-methyl]-1- azabicyclo[2.2.2]octan-3-amine (L-703606) inhibits binding of 125I-Tyr8-substance P to the human NK1 receptor with an IC50 of 2 nM. This compound is a competitive antagonist of substance P-induced inositol phosphate generation, with a Kb of 29 nM. [125I]L-703606 binds to a single class of high affinity binding sites in human NK1/Chinese hamster ovary cell membranes (Kd = 0.3 nM). Substance P inhibits the binding of [125I]L-703606 to 65% of the NK1 receptor sites with a Kd of 0.04 +/- 0.03 nM and to the remaining 35% of the sites with a Kd of 1.5 +/- 0.7 nM. Addition of the nonhydrolyzable GTP analog guanylyl-5'-(beta, gamma-imido)diphosphate [Gpp(NH)p] shifts greater than 90% of the binding sites to the lower affinity state. In addition, Gpp(NH)p markedly alters the dissociation of substance P from the NK1 receptor by increasing the number of sites in the low affinity, rapidly dissociating state. However, Gpp(NH)p does not affect the rate of dissociation of [125I]L-703606. These data suggest that the pharmacological properties of [125I]L-703606 binding to the human NK1 receptor are similar to those of antagonists of nonpeptide guanine nucleotide-binding protein-coupled receptors and that this ligand will be useful for the biochemical and pharmacological characterization of the human NK1 receptor.

Amino Acid Sequence↗

The NPXY internalization signal of the LDL receptor adopts a reverse-turn conformation.

Peptides corresponding to the proposed coated pit internalization signal of the native low density lipoprotein receptor, NPVY, take up in aqueous solution a reverse-turn conformation with the Asn in position i and the Tyr in position i + 3. By contrast, peptides derived from receptors that are defective for endocytosis do not adopt the reverse turn. These internalization-defective receptors include those with a nonaromatic residue substituted for the Tyr and those with Asn----Ala or Pro----Ala substitutions. While the tendency of an Asn-Pro sequence to induce a reverse turn was anticipated, the structural importance of an aromatic residue in position i + 3 was not. The sequences associated with the internalization signal thus appear to play a critical conformational role that is required for endocytosis, probably by enabling binding to adaptor molecules. With the results presented in the accompanying paper on lysosomal acid phosphatase, we now have direct evidence for previous proposals of a general correlation of internalization signals with a turn conformational motif.

Amino Acid Sequence↗

Infant feeding practices in educated mothers from upper socio-economic status.

One hundred and twenty mothers from upper socio-economic status and education up to graduation level were assessed for infant feeding practices using a pre-tested questionnaire. Prelacteal feed of honey was administered by 51.7% and initiation of breast feeding delayed by more than 24 hours by 68.3% of mothers. Colostrum was discarded by 53% mothers; 83% introduced bottle feeding in the first month of life; and poor bottle hygiene was seen in 54% cases. Addition of semisolids was delayed by almost 50% of mothers, the reason given being fear of liver disorders. These observations highlight ignorance about basic infant feeding practices in the educated elite section of our country. Health education in schools, colleges, non formal gatherings and during the antenatal period are suggested as means to remove this ignorance.

Bottle Feeding↗