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Biomedical subjects

S Haque

Publications and source records attributed to S Haque.

At least 73 records · Page 4Linked to original sources

Autoreactivity of low but not of high CD4 variants of an antigen-specific, I-A-restricted mouse T cell clone.

Variant lines expressing high and low surface densities of the accessory molecule CD4 have been developed by repeated preparative flow cytometric cell sortings from the murine Th cell clone D10.G4.1 (D10). The high CD4 variant line (D10H) fully maintained the original I-Ak restricted specificity for conalbumin of wild-type D10 cells. In contrast, the low CD4 variant line (D10L) showed a strong autoreactivity to I-Ak carrying stimulator cells alone which was only slightly augmented by addition of conalbumin. Cell surface molecules other than CD4, including TCR, CD3, CD11a, CD2, CD45, CD44, and MHC class I, remained identical on D10H and D10L sublines as on D10 wild-type cells. The possibility that D10L cells had suffered alterations of their TCR-alpha beta was excluded by demonstrating their reactivity with a panel of eight different anti-clonotypic mAb specific for various epitopes of the D10 TCR. By limiting dilution analysis we show that the majority of responding cells of D10L sublines were autoreactive. Although the reactivity for allogeneic I-A also increased as compared with D10H cells, a clear preference for self-I-Ak was maintained so that a true autoreactive phenotype was evident. The results indicate that the surface concentration of CD4 has a decisive influence on self-non-self discrimination of MHC class II-restricted Th cells.

Animals↗

Stromal neoplasms of the rectum and anal canal.

Nineteen mural-based stromal tumors of the rectum and anal canal were reviewed, with the objective of delineating pathologic features discriminative of malignancy in these uncommon neoplasms. Ten locally excised tumors failed to recur during long-term follow-up and were considered benign. All occurred in the submucosa and ranged in size from 1.0 to 7.0 cm (mean, 2.1 cm). Three were sparsely cellular; seven had the appearance of gastric-type cellular leiomyomas. All lacked nuclear atypia and displayed mitotic activity not exceeding 1 mitosis/50 high-power microscopic fields. In contrast, of nine tumors exhibiting malignant behavior, eight (89%) were located in the muscularis propria. Their mean size was 4.5 cm (range, 1.6 to 11 cm). Necrosis was present in six tumors (67%). Seven sarcomas retained a cellular leiomyomatous appearance but exhibited moderate cytologic atypia. Mitotic counts ranged from 5 to 58 mitoses/50 high-power microscopic fields. Three locally excised sarcomas recurred in the rectum at 2, 2, and 7 years. In five patients tumor recurred in the pelvis. Five patients died of disease 0.67, 1.2, 3, 5, and 11 years post-diagnosis. One patient died with sarcoma at 31 years. Three patients are without evidence of recurrent neoplasm 5, 5, and 7 years postresection. Our data indicate that not all anorectal, mural-based stromal neoplasms are a priori malignant. While location within the muscularis propria, size, nuclear atypia, and tumoral necrosis correlate with malignancy, mitotic activity is the cardinal indicator of sarcomatous behavior in stromal neoplasms of the rectum and anal canal.

Adult↗

Multiple glomus tumors of the stomach with intravascular spread.

Gastric glomus tumors are characteristically benign solitary lesions. We present a case of multiple glomus tumors involving the stomach wall and perigastric adipose tissue. Histologically, the major portion of each tumor was composed of "typical" glomus cells arranged in a predominantly solid pattern. Cavernous hemangiomalike areas were present toward the periphery. The tumor cells were immunoreactive for alpha-smooth muscle actin, vimentin, laminin, and type IV collagen, but did not express desmin. There were several focal areas where the tumor cells had a signet-ring cell-like appearance, intermingled with cells having clear cytoplasm and hyperchromatic nuclei. Rare mitoses were noted. A striking feature was the presence of widespread but subtle extension of the glomocytes along venous channels subendothelially, with formation of intravascular nodules focally. The multiple separate tumor nodules found in perigastric fat are interpreted as having arisen in this manner. This entity is distinct from previously described typical and atypical solitary glomus tumors, glomangiosarcoma, and the syndrome of multiple glomus tumors of subcutaneous tissues. It may represent an early stage of development of the large, multilobulated glomus tumors that have rarely been reported to involve stomach and adjacent viscera.

Aged↗

A cecal diaphragm associated with the use of nonsteroidal anti-inflammatory drugs.

In the small intestine, strictures and diaphragms causing obstructive symptoms are well known to occur in patients using nonsteroidal anti-inflammatory drugs. Recently, two cases of nonsteroidal anti-inflammatory drug (NSAID)-associated diaphragm-like colonic stricture were reported as unexpected findings in patients being investigated for iron-deficiency anemia. We present a third such case that occurred in the cecum in a 49-year-old woman with rheumatoid arthritis who had been taking NSAIDs for 5 years.

Anti-Inflammatory Agents, Non-Steroidal↗

Diversion colitis--20 years a-growing.

During the last decade, clinical and pathologic studies of diversion colitis have led to a better understanding of its nature. The clinical features are well described, and the endoscopic appearances, and gross and microscopic pathology are now defined. Thus, firm diagnosis and distinction from other colitides, notably ulcerative colitis and Crohn's disease, are possible in most cases. Restoration of the fecal stream cures diversion colitis, which in some cases may be successfully treated with short-chain fatty acid enemas, although the efficacy of this method remains to be substantiated. An understanding of the pathogenesis of diversion colitis (currently unknown) may lead to better methods of prevention and treatment.

Colitis↗

Perceived workload and performance of shift workers.

The present paper is based on the results of a study conducted to investigate whether the relationship between perceived workload and quality of performance, if any, holds true if controlled for shift system, type of task, age, and skill level of the workers. The sample of the study comprised 279 blue-collar workers of a jute industry operating under fixed three-shift system. The subjects were all males selected by random sampling method. The method of data collection was a field study through questionnaire. The collected data were analyzed by employing zero-order and partial correlation coefficients. The results indicate that workload and performance were negatively correlated but the strength of the relationship reduced substantially when the effects of the control variables were partialled out simultaneously. It was concluded that the control variables had joint effect on the relationship between workload and performance but skill level of the employees appeared to be the variable having the greatest contaminating effect.

Adolescent↗

Induction of heme oxygenase mRNA by cobalt protoporphyrin in rat liver.

The effect of cobaltic(III)-protoporphyrin on heme oxygenase activity and mRNA content was examined in vivo in the adult male rat liver. The activity of heme oxygenase, the rate-limiting enzyme in the degradation of heme, was enhanced, as expected, by cobalt protoporphyrin (25 mumol/kg body weight) in a time-dependent manner. Levels of enzyme activity were increased 2-fold by 8-16 h following treatment and were 6-fold higher than baseline values by 48 h. Administration of cobalt protoporphyrin resulted in a marked increase in heme oxygenase mRNA in the liver. Within 2 h of treatment, mRNA levels had increased 7.9-fold. The induction of heme oxygenase mRNA was maximal at 8 h when the levels were 58.5-fold above baseline. At every time point tested, the increase in heme oxygenase mRNA was several fold greater than that of enzyme activity.

Animals↗

Fibular hypoplasia and complex brachydactyly (Du Pan syndrome) in an inbred Pakistani kindred.

A Pakistani kindred comprising 7 generations contained 7 men and 2 women with fibular hypoplasia and complex brachydactyly (syn: Du Pan syndrome). Analysis of the pedigree is strongly suggestive of autosomal recessive inheritance. The average inbreeding coefficient (F) for the affected persons was found to be significantly greater than that for unaffected persons in the pedigree and consanguineous loops could account for all affected persons being homozygous for the abnormal allele.

Consanguinity↗

A monoclonal antibody to Ly-6 gene product inhibits generation of functionally active T cells and recognizes single antigenic specificity whose expression is up-regulated in virus-transformed rat fibroblast.

In order to elucidate the relationship between the structure and function of proteins encoded for by the Ly-6 gene complex, a cDNA was constructed for a Ly-6.2 specificity and then monoclonal antibodies (mAb) generated to bacterially synthesized protein. The addition of one of these mAb, designated Pb-19, inhibited the proliferative response of T cells to concanavalin A (Con A) or major histocompatability complex (MHC) alloantigens. Reactivity of Pb-19 to the Ly-6 specificity was blocked by a known anti-Ly-6.A.2 mAb but not by an anti-Ly-6.E.1 mAb. This mAb detected a Ly-6.A.2 specificity (a 33,000 MW antigen) whose expression was increased in a transformed rat fibroblast containing the entire genome of bovine papillomavirus.

Animals↗

The influence of valence on the functional activities of monoclonal anti-L3T4 antibodies. Discrimination of signaling from other effects.

Anti-L3T4 antibodies have different functional effects on different ligands that activate a cloned, L3T4+ helper T cell line. It is reported here that some of these effects involve positive or negative signaling induced by cross-linking L3T4 molecules, because such effects are not observed using the Fab fragment of anti-L3T4. However, the Fab fragment does inhibit responses to antigen:self class II major histocompatibility complex (MHC) and to anti-T cell receptor monoclonal antibodies directed at a particular V region epitope. The finding that the Fab fragment of anti-L3T4, which does not block binding of anti-T cell receptor V region antibodies and does not negative signal can still block activation by such antibodies suggests an intimate association of L3T4 with the T3: alpha: beta T cell receptor complex. This association may normally be induced by interaction of both structures with antigen:self class II MHC complexes. The data also support the hypothesis that cross-linking the L3T4 molecule in the absence of engagement of the T3: alpha: beta complex generates negative or inhibitory signals. Thus, L3T4 plays a central role in the process of class II MHC-restricted T cell antigen recognition and activation.

Animals↗

X-chromosomally inherited split-hand/split-foot anomaly in a Pakistani kindred.

A Pakistani kindred comprising seven generations and 36 members with the split-hand/split-foot anomaly is described. The full expression of the trait, monodactylous or split hand and split foot, mainly of the lobster-claw type, was present in 33 males and 3 females. Other females showed a distinctly milder expression of the trait, usually in the form of partial syndactyly, metacarpal and phalangeal hypoplasia, and malformation. The distribution of the affected members in the pedigree is compatible with X-chromosomal inheritance. Hemizygous males and presumably homozygous females exhibit the typical split-hand/split-foot anomaly, whereas only a part of the obligatory heterozygous females show the milder expression. There were no associated anomalies, such as ectodermal dysplasia, cleft lip/palate, macular degeneration, malformations of the long bones or internal organs, and overt mental retardation.

Abnormalities, Multiple↗

The role of the murine L3T4 molecule in T cell activation: differential effects of anti-L3T4 on activation by monoclonal anti-receptor antibodies.

MHC restricted T cells can be divided into two subsets based on the mutually exclusive expression of the cell surface differentiation antigens L3T4 and Lyt-2 in the mouse. Expression of the L3T4 marker is correlated most strictly with recognition of foreign antigen in association with self class II MHC molecules, or Ia molecules. Less stringently correlated with L3T4 expression is the recognition of unmodified self or non-self Ia molecules. Finally, expression of L3T4 is also correlated with certain functional properties, although this correlation is even less stringent. The major correlation for function is between L3T4 and the ability to activate B cells. These correlations have led to the hypothesis that L3T4 recognizes Ia molecules, and plays a role in increasing the affinity of T cell:Ia bearing cell interactions. This hypothesis is bolstered by the finding that anti-L3T4 antibody blocks such interactions. Recently, we and others proposed a second effect of cross-linking L3T4 molecules, namely negative signalling. We further proposed that the natural ligand for L3T4 is Ia molecules, and that Ia-driven cross-linking of L3T4 molecules on the T cell in the absence of receptor aggregation would lead to off signalling to the T cell and separation of cell conjugates. To better understand the role of the L3T4 molecule in T cell activation, we have examined the effect of several anti-L3T4 antibodies on stimulation of a cloned line of helper T cells by a panel of monoclonal antibodies directed at what appear to be different epitopes on the T cell receptor. Unlike previous analyses of stimulation of helper T cells with anti-T cell receptor antibodies, we observe differential effects of anti-L3T4 on T cell activation by anti-receptor antibodies, the effect of anti-L3T4 depending on the characteristics of the anti-receptor antibody. This result suggests that L3T4 is intimately associated with the T cell receptor, and may thus play a critical role in T cell specificity as part of the antigen:Ia recognition complex. This proposed role is in keeping with the very strong correlation between L3T4 expression and recognition of self class II MHC molecules. While these studies do not provide definitive evidence for a physical association between L3T4 and the T cell receptor, they do place certain constraints on current models and suggest new possibilities for understanding T cell recognition and development.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Antigenicity of native and modified Kunitz soybean trypsin inhibitors.

Food provides a continuous antigenic stimulus to the immune system and the antigenicity of processed food proteins should be considered in toxicological evaluations. The antigenicity of the Kunitz trypsin inhibitor was studied using antibodies prepared by inoculating rabbits with native, heat-denatured, and N-acetylcysteine-treated Kunitz soybean trypsin inhibitors. Immunochemical studies using a competitive solid-phase enzyme immunoassay and two groups of sera revealed two patterns of antigenicity. Antibodies elicited with the denatured inhibitor were specific for the denatured conformation of the protein. In contrast, native inhibitor elicited antibodies that selectively recognized determinants in both native and heat-treated protein, but that did not bind trypsin inhibitors treated with N-acetylcysteine. These results imply that: the disulfide bonds must be intact to maintain the native antigenic conformation and the cysteine treatment may suppress allergic manifestations of soybean trypsin inhibitors and possibly other food proteins. These studies were extended by analyzing a panel of monoclonal antibodies prepared against native Kunitz trypsin inhibitor. The inhibitor has at least two distinct antigenic sites (epitopes), one of which is retained under denaturing conditions. The measurement of native Kunitz trypsin inhibitor in food samples by immunoassay appears practical. The relevance of these findings to food processing, food safety, and health is also discussed.

Animals↗

Structure of the Tetrahymena pyriformis rRNA gene. Nucleotide sequence of the transcription initiation region.

Portions of rRNA gene repeat from Tetrahymena pyriformis were cloned in pBR322, and a subclone containing the transcription initiation site was isolated. The promoter region was identified by S1 nuclease mapping of a portion of the HindIIIB fragment of the rRNA gene, using the 35 S rRNA primary transcript as a probe. The nucleotide sequence of the initiation site and the 5'-flanking region reveals three sets of highly conserved repeat sequences. A model of the promoter region is presented in which the rDNA is wrapped around a series of histone octamers. In this model the families of repeat sequences are brought in close proximity and suggest several possible mechanisms for the regulation of rRNA synthesis in T. pyriformis.

Animals↗