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Biomedical subjects

I A Khatri

Publications and source records attributed to I A Khatri.

10 recordsLinked to original sources
PubMed2006

MS in Asian countries.

This paper reviews all available English language literature on MS from Asian countries published between 1970 and 2005. Although limited data are available, the review reveals that western Asia--including the Middle East--has the highest prevalence of MS across the continent, and that MS in Asia largely resembles conventional MS in western countries. Opticospinal MS (a distinct clinical entity from conventional MS) is more common in eastern Asian regions. Larger epidemiological and genetic studies, with more complete ascertainment in various Asian populations, are needed so that we can understand the diversity of Asian MS.

Adult↗
PubMed2003

Epidemiology of epilepsy in Pakistan: review of literature.

OBJECTIVE: To review literature pertinent to the epidemiology of epilepsy in developing countries with special reference to Pakistan. METHODS: All the studies published in medical journals related to epilepsy in Pakistan were systematically reviewed. Important findings from various studies are summarized. RESULTS: Overall prevalence of epilepsy in Pakistan is estimated to be 9.99 per 1000 population. Highest prevalence is seen in people younger than 30 years of age. A slight decrease in prevalence is noted between the ages of 40 and 59. Higher prevalence is observed in rural population. Etiology of epilepsy is more commonly identified in pediatric population. Epilepsy was considered idiopathic in 21 to 76% cases. Only 27.5% epileptic persons in urban areas and 1.9% in the rural areas were treated with AEDs. The burden of epilepsy is not fully evaluated and understood. Generalized seizures were the most common seizure type noted. Knowledge about epilepsy and its care is extremely low. CONCLUSION: Epilepsy is a common medical problem in Paksitan, more prevalent is rural population. The majority of people with epilepsy are treated inadequately or inappropriately.

Adolescent↗
PubMed2001

Characteristics of rodent intestinal mucin Muc3 and alterations in a mouse model of human cystic fibrosis.

Human mucin MUC3 and rodent Muc3 are widely assumed to represent secretory mucins expressed in columnar and goblet cells of the intestine. Using a 3'-oligonucleotide probe and in situ hybridization, we observed expression of rat Muc3 mostly in columnar cells. Two antibodies specific for COOH-terminal epitopes of Muc3 localized to apical membranes and cytoplasm of columnar cells. An antibody to the tandem repeat (TR) sequence (TTTPDV)3, however, localized to both columnar and goblet cells. On CsCl gradients, Muc3 appeared in both light- and heavy-density fractions. The lighter species was immunoreactive with all three antibodies, whereas the heavier species reacted only with anti-TR antibody. Thus Muc3 is expressed in two forms, a full-length membrane-associated form found in columnar cells (light density) and a carboxyl-truncated soluble form present in goblet cells (heavy density). In a mouse model of human cystic fibrosis, both soluble Muc3 and goblet cell Muc2 were increased in amount and hypersecreted. Thus Muc2 and Muc3 contribute to the excess intestinal luminal mucus of cystic fibrosis mice.

Amino Acid Sequence↗
PubMed1998

Susceptibility of the cysteine-rich N-terminal and C-terminal ends of rat intestinal mucin muc 2 to proteolytic cleavage.

The present study reveals that partial proteolytic degradation of rat Muc 2 mucin can occur rapidly even in the presence of a battery of proteinase inhibitors. During the initial steps of purification from homogenates of intestinal scrapings, degradation was rapid, causing release of the entire 118 kDa C-terminal glycopeptide and, as shown by N-terminal sequencing, a large (200 kDa) N-terminal glycopeptide fragment. Degradation could be prevented by adding 6 M guanidinium chloride provided that its presence was maintained throughout every step of purification. Even after purification, however, the mucin was still vulnerable to partial proteolysis unless it was stored in guanidinium chloride at -20 degrees C. These findings imply that a potent proteinase contaminant remains tightly bound to the mucin through every step of purification, or else that the mucin has autocatalytic properties. Because the C- and N-terminal regions of secretory mucins are required for their assembly into linear mucin polymers that form functional gels, our findings emphasize that extreme care is required to purify structurally intact mucin molecules. They also imply that the specific degradation steps described here are likely to occur rapidly after mucins are secreted into the intestinal lumen and come into contact with the products of sloughed cells.

Alkylation↗
PubMed1998

Evidence that a peptide corresponding to the rat Muc2 C-terminus undergoes disulphide-mediated dimerization.

We have investigated the possibility that the intestinal mucin rat Muc2 forms dimers during biosynthesis via intermolecular disulphide bridging of its C-terminal domains. Since the cysteine alignment of RMuc2 (and other secretory mucins) is similar to that of human von Willebrand factor, a similar C-tail to C-tail dimerization may occur in mucins. The C-terminal domain of RMuc2 (534 amino acids) was expressed in COS-1 cells, and the products monitored by SDS/PAGE and western blotting with three antibodies to different regions of the C-terminal domain. In cells, the expressed domain was glycosylated and formed disulphide-dependent dimers centred at approximately 150 kDa. The domain dimer, but not its precursor monomer, was secreted into the culture medium. The dimers in the media however, appeared to be 12-15-kDa heavier (i.e. had a slower mobility) than in cell lysates. Initial N-glycosylation, dimerization and secretion were inhibited by addition of tunicamycin to incubations, whereas benzyl-alpha-GalNAc did not interfere with these processes. However benzyl-alpha-GalNAc resulted in a decrease in the apparent size of secreted dimers, such that they now had the same mobility on gels as dimers normally seen in cell lysates (i.e. 150 kDa). A similar change in dimer size was observed after incubating untreated media samples with N-acetylneuraminidase. This suggests that benzyl-alpha-GalNAc caused inhibition of sialylation of cell dimers just before they were secreted. In summary, the C-terminal domain of RMuc2 can form disulphide-dependent dimers, and N-glycosylation is required for dimerization and subsequent secretion. A late sialylation event appears to precede the secretion of mucin domain dimers.

Acetylgalactosamine↗
PubMed1996

Cloning of the cDNA for a rat intestinal Na+/dicarboxylate cotransporter reveals partial sequence homology with a rat intestinal mucin.

In this report we present the full-length cDNA and deduced 587 amino acid sequence of a putative rat intestinal Na+/dicarboxylate cotransporter. It shows sequence and structural similarity to a rabbit renal Na+/dicarboxylate cotransporter. An unexpected fining was the presence of a C-terminal transmembrane region that is homologous with an 87 amino acid hydrophobic region of a rat intestinal mucin, M2. Mucin-related sequences in transporter proteins have not been described before.

Amino Acid Sequence↗
PubMed1994

Intestinal mucins inhibit rotavirus replication in an oligosaccharide-dependent manner.

Rotaviruses are important causes of infant morbidity and mortality worldwide. It has been previously shown that mucinous glycoproteins can inhibit rotavirus replication. However, the structure-function relationships of this inhibition have not been completely elucidated. Mucins were purified from epithelial scrapings of rat and human intestine by CsCl density-gradient ultracentrifugation and tested for the inhibition of rotavirus replication in MA-104 cells. Native human and rat intestinal mucins inhibited the replication of human and animal rotaviruses at low concentrations. Antiviral activity was most prominent in the densely glycosylated part of the rat and human mucins. Activity was retained after thiol reduction and alkylation, chloroform methanol partition, and partial removal of oligosaccharides. However, total deglycosylation of the mucins destroyed antiviral activity. Intestinal mucins from humans and other animals are potent inhibitors of rotavirus replication, and this inhibition is dependent on specific mucin-viral interactions.

Adult↗
PubMed1993

Suggestive evidence for two different mucin genes in rat intestine.

In the present report we describe the isolation and sequence of a partial cDNA (M2-798) for a rat intestinal mucin designated M2. A rat intestinal lambda ZAP II cDNA library was screened using a polyclonal antiserum which was prepared against deglycosylated high-molecular-mass glycopeptides of the purified mucin. Mucin cDNA clones were found to contain tandem repeats of 18 nt which encoded a threonine- and proline-rich peptide having a consensus sequence of TTTPDV. This is the same sequence reported recently by Gum, Hicks, Lagace, Byrd, Toribara, Siddiki, Fearney, Lamport and Kim [(1991) J. Biol. Chem. 266, 22733-22738] for a rat intestinal cDNA called RMUC 176. A novel feature present in the cDNA M2-798 is a 246 nt unique region at the 3' end which encodes a hydrophobic sequence of 82 amino acids. RNA blots probed with M2-798 cDNA produced a single hybridization band between 7.5 and 9.0 kb in rat small intestine and colon. An identical hybridization pattern was obtained with a PCR-generated cDNA probe corresponding solely to the unique hydrophobic region of M2-798, demonstrating that this region is encoded by the authentic M2 mRNA. Our data suggest that the unique region of M2 has the potential to be either a transmembrane region, or a domain which mediates hydrophobic interactions of the mucin with other molecules. Since we have previously reported another rat intestinal cDNA which encodes the C-terminus of a mucin-like peptide (MLP) [Xu, Wang, Huan, Cutz, Forstner and Forstner (1992) Biochem. J. 286, 335-338], we wished to discover whether M2 was encoded by the same gene. RNA blotting experiments with probes specific for M2 and MLP showed different mRNAs for each. The message for M2 (7.5-8.5 kb) was smaller than that for MLP (> 9.5 kb) and, unlike MLP, gave no signal in human colonic LS174T cells. The results of DNA blots probed with M2-798 and an MLP-probe suggest that M2 and MLP are likely to be single-copy genes. It would appear therefore that normal rat intestine, like human intestine, may express two different mucin genes.

Animals↗
PubMed1992

cDNA for the carboxyl-terminal region of a rat intestinal mucin-like peptide.

When subjected to thiol reduction, purified intestinal mucins have been shown to undergo a decrease in molecular mass and to liberate a 118-kDa glycopeptide (Roberton, A. M., Mantle, M., Fahim, R. E. F., Specian, R., Bennick, A., Kawagishi, S., Sherman, P., and Forstner, J. F. (1989) Biochem. J. 261, 637-647). The latter has been called a putative "link" component because it is assumed to be important for disulfide bond-mediated mucin polymerization. Controversy exists as to whether the putative link is an integral mucin component or a separate mucin-associated glycopeptide. In the present study both NH2-terminal and internal amino acid sequences of the 118-kDa glycopeptide of rat intestinal mucin were used to generate opposing oligonucleotide primers for polymerase chain reaction. A specific 1.2-kilobase (kb) product was obtained, from which a 0.5-kb HindIII fragment was used as a probe to screen a lambda ZAP II cDNA library of rat intestine. A 2.6-kb cDNA (designated MLP 2677) was sequenced and revealed an open reading frame of 2.5 kb encoding 837 amino acids. The deduced amino acid sequence showed that the putative link peptide is equivalent to the carboxyl-terminal 689 amino acids of a larger peptide. Northern blots revealed a mRNA size of approximately 9 kb. Computer searches revealed no sequence homology with other proteins, but similarities were seen in the alignment of cysteine residues in the link and in several domains of human von Willebrand factor, as well as cysteine-rich areas of bovine and porcine submaxillary mucins and a frog skin mucin designated FIM-B.1. In keeping with earlier demonstrations of the presence of mannose in the 118-kDa glycopeptide, there were several (13) consensus sequences for attachment of N-linked oligosaccharides within the link domain. Further sequencing of MLP 2677 in a direction 5' to the codon specifying the NH2-terminal proline of the link has revealed a coding region for 148 amino acids, including a unique 75-amino acid domain rich in cysteine and proline, and a region containing 4.5-variable tandem repeats (each 11-12 amino acids) rich in serine, threonine, and proline. The presence of mucin-like tandem repeats suggests that the entire cysteine-rich link peptide represents the carboxyl-terminal region (75.5 kDa) of a mucin-like peptide (MLP). The latter is estimated to have a molecular mass of approximately 300 kDa.

Amino Acid Sequence↗