Search PubMed⌕ Search

Biomedical subjects

A Khurana

Publications and source records attributed to A Khurana.

At least 19 recordsLinked to original sources

Glycolipid antigen processing for presentation by CD1d molecules.

The requirement for processing glycolipid antigens in T cell recognition was examined with mouse CD1d-mediated responses to glycosphingolipids (GSLs). Although some disaccharide GSL antigens can be recognized without processing, the responses to three other antigens, including the disaccharide GSL Gal(alpha1-->2)GalCer (Gal, galactose; GalCer, galactosylceramide), required removal of the terminal sugars to permit interaction with the T cell receptor. A lysosomal enzyme, alpha-galactosidase A, was responsible for the processing of Gal(alpha1-->2)GalCer to generate the antigenic monosaccharide epitope. These data demonstrate a carbohydrate antigen processing system analogous to that used for peptides and an ability of T cells to recognize processed fragments of complex glycolipids.

Amino Acid Motifs↗

Thermodynamic characterization of mutants of human fibroblast growth factor 1 with an increased physiological half-life.

Human acidic fibroblast growth factor (FGF-1) is a potent mitogen and angiogenic factor, with reportedly poor thermal stability and a relatively short in vivo half-life. However, certain mutants of FGF-1 have been described that exhibit a significant increase in half-life in tissue culture-based assays. FGF-1 contains three cysteine residues, two of which are highly conserved and buried within the protein core. Mutant forms of FGF-1 that substitute a serine residue at these cysteine positions have been reported to increase the protein's half-life and specific activity as well as decrease the dependence upon heparin for full activity. However, the underlying physical basis for this increase in half-life has not been determined. Possible effects include stabilization of protein structure and elimination of sulfhydryl chemistry at these positions. Here we have used differential scanning calorimetry and isothermal equilibrium denaturation to characterize thermodynamic parameters of unfolding for individual, and combination, cysteine to serine mutations in human FGF-1. The results show that substitution by serine is destabilizing at each cysteine position in wild-type FGF-1. Thus, the increased half-life previously reported for these mutations does not correlate with thermal stability and is most likely due to elimination of sulfhydryl chemistry. The results also suggest a method by which protein half-life may be modulated by rational design.

Calorimetry, Differential Scanning↗

Alteration of sonographic texture of the endometrium in post-menopausal bleeding. A guide to further management.

BACKGROUND: The purpose of this study was to assess the utility of transvaginal ultrasonography in the evaluation of endometrial morphology in addition to the standard criterion of endometrial thickness for selecting patients for endometrial sampling. METHODS: Two hundred and seven consecutive cases of postmenopausal bleeding were evaluated by transvaginal ultrasound. Endometrial thickness was measured as the maximum anteroposterior thickness of the endometrium including both the anterior and posterior layers, in the sagittal long axis view. The morphology of the endometrium was studied and categorized as homogeneous, focally increased echogenecity, diffusely increased echogenecity or diffusely inhomogeneous. Patients were followed up for clinical course and endometrial histopathology. RESULTS: Textural inhomogeneity was observed in all the three cases of endometrial cancers with endometrial thickness of less than 6 mm, and, in ten out of 11 cases of a more than 6 mm thick endometrium. On the other hand the endometrial texture was homogeneous in all cases of endometrial atrophy/tissue inadequate for diagnosis, with thickness of less than 6 mm. CONCLUSION: This study adds the dimension of abnormal echogenecity of the endometrium to the currently followed criterion of endometrial thickness with a view to enhance accuracy, both for a better prediction of atrophy and a higher prediction for endometrial cancer. Expectant management can be offered to patients with a homogeneous endometrium which is 6 mm thick or less. Aggressive evaluation for a malignancy must be made if there is a focal increased echogenecity or a diffuse increased echogenecity even in a thin endometrium.

Adult↗

Reversible thermal denaturation of human FGF-1 induced by low concentrations of guanidine hydrochloride.

Human acidic fibroblast growth factor (FGF-1) is a powerful mitogen and angiogenic factor with an apparent melting temperature (Tm) in the physiological range. FGF-1 is an example of a protein that is regulated, in part, by stability-based mechanisms. For example, the low Tm of FGF-1 has been postulated to play an important role in the unusual endoplasmic reticulum-independent secretion of this growth factor. Despite the close relationship between function and stability, accurate thermodynamic parameters of unfolding for FGF-1 have been unavailable, presumably due to effects of irreversible thermal denaturation. Here we report the determination of thermodynamic parameters of unfolding (DeltaH, DeltaG, and DeltaCp) for FGF-1 using differential scanning calorimetry (DSC). The thermal denaturation is demonstrated to be two-state and reversible upon the addition of low concentrations of added guanidine hydrochloride (GuHCl). DeltaG values from the DSC studies are in excellent agreement with values from isothermal GuHCl denaturation monitored by fluorescence and circular dichroism (CD) spectroscopy. Furthermore, the results indicate that irreversible denaturation is closely associated with the formation of an unfolding intermediate. GuHCl appears to promote reversible two-state denaturation by initially preventing aggregation of this unfolding intermediate, and at subsequently higher concentrations, by preventing formation of the intermediate.

Calorimetry, Differential Scanning↗

Failure of autoresuscitation in weanling mice: significance of cardiac glycogen and heart rate regulation.

"Autoresuscitation" (AR) is the spontaneous recovery from hypoxic apnea by gasping. We examined aspects of heart function in two situations: 1) the maturationally acquired failure of AR that is characteristic of SWR, but not BALB/c, weanling mice and 2) AR failure in BALB/c mice induced by repeated exposures to anoxia. We determined maturational changes in heart and liver glycogen. Unlike liver glycogen levels, heart glycogen levels in SWR mice differed from those in BALB/c mice. They were consistently much lower throughout maturation and reached a nadir during the brief period when SWR weanling mice are vulnerable to AR failure. Also, rate of cardiac glycogen utilization in vulnerable SWR mice was lower than that of same-aged BALB/c mice and was nil during the latter one-half of the gasping stage when heart function is critical for AR success. Therefore, because glycogen utilization reflects cardiac work, heart failure could explain AR failure in SWR weanlings. Additionally, the increase in hypoxic heart rate that occurs with maturation is developmentally delayed in SWR mice, and this may contribute to their AR failure. Cardiac glycogen was not fully depleted in BALB/c mice during repeated anoxic exposures, indicating other reasons for AR failure. We view these findings as a potential model for the age-related peak in incidence of sudden infant death syndrome.

Age Factors↗

An infant with a mosaic 45,X/46,X,psu dic(Y) (pter-->q11.2::q11.2-->pter) karyotype and mixed gonadal dysgenesis studied for extent of mosaicism in the gonads.

AN infant with mixed gonadal dysgenesis was found to have a 45,X/46,Xpsu dic(Y) karyotype. A low level (8%) of mosaicism for the dic(Y) cell line was observed in peripheral blood lymphocytes and skin fibroblasts. The dicentric nature of the Y chromosome became apparent in fluorescence in situ hybridization studies. The presence of Y centromeric sequences was demonstrated in the paraffin-embedded testis and streak ovary sections. The ration of Y-positive cells was higher in the testis than in the streak ovary.

Chromosome Aberrations↗

Effects of upper airway stimulation on swallowing, gasping, and autoresuscitation in hypoxic mice.

Severe hypoxia produces a state of neural depression known as hypoxic coma in which reflex activity is believed to be absent but from which spontaneous recovery ("autoresuscitation") still can occur. We evaluated the swallowing reflex during hypoxic coma by employing mechanical and chemosensory stimuli. BALB/c mice were given 97% N2-3% CO2 to breathe. At onset of coma, a 0.05-ml bolus of saline or water was infused into the pharynx. Unlike mechanical stimulation (sham infusion), fluid infusion usually was followed by rapid swallowing, more so with water than with saline. This model allowed examination of interactions among swallowing, hypoxic gasping, airway fluid removal, and autoresuscitation. Compared with sham infusion, saline and water reduced gasping rate equally. Saline, however, prolonged the process of autoresuscitation more than did water, an effect possibly related to an observed increased retention of saline in the airway. Occasionally, mice failed to swallow after infusions, in which case airway obstruction during gasping and autoresuscitation failure was repeatedly observed. These studies suggest that the swallowing component of the laryngeal chemoreflex is present during hypoxic coma and that swallowing facilitates autoresuscitation when upper airway fluid is present.

Animals↗

Caroli disease: computed tomographic diagnosis.

Computed tomographic (CT) scan findings in patients with cavernous ectasia of the biliary tract (Caroli disease) have been described. Our patient had the isolated form of Caroli disease characterized by saccular dilatation of intrahepatic bile ducts and no evidence of portal hypertension. CT scan of the liver showed tiny dots with strong contrast enhancement within dilated intrahepatic bile ducts (the central dot sign). This finding when correlated with sonogram indicated portal radicles surrounded by dilated intrahepatic bile ducts.

Adolescent↗

Limits d-->

Explore the source record for details and available documents.

Journal Article↗