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Biomedical subjects

D Rahman

Publications and source records attributed to D Rahman.

28 records · Page 2Linked to original sources

IgA subclasses in HIV disease: dichotomy between raised levels in serum and decreased secretion rates in saliva.

This study sought to determine IgA, IgA1 and IgA2 concentrations and secretion rates in unstimulated whole saliva and stimulated parotid saliva and IgA, IgA1 and IgA2 concentrations in serum from asymptomatic human immunodeficiency virus (HIV)-infected, acquired immune deficiency syndrome (AIDS) and control subjects. In whole and parotid saliva the mean IgA, IgA1 and IgA2 concentrations in the HIV and AIDS groups were lower than the control group (P < 0.05). Unstimulated whole and stimulated parotid saliva flow rates were lower in the HIV and AIDS groups compared with the control group, and reached statistical significance with respect to the mean parotid saliva flow rate in the AIDS group (P < 0.05). Mean IgA, IgA1 and IgA2 secretion rates in both the HIV and AIDS groups were significantly less than the controls (P < 0.05). In contrast, serum IgA, IgA1 and IgA2 concentrations were markedly raised in the HIV and AIDS groups compared with the control group (P < 0.001). There was no correlation between saliva and serum IgA concentrations within individuals. This study suggests that, in spite of the raised, polyclonally activated serum IgA concentrations associated with HIV infection, salivary IgA concentrations and secretion rates are reduced, emphasizing the dichotomy between systemic and secretory immunity.

Acquired Immunodeficiency Syndrome↗

Identification and preliminary characterization of a protein motif related to the zinc finger.

We have identified a protein motif, related to the zinc finger, which defines a newly discovered family of proteins. The motif was found in the sequence of the human RING1 gene, which is proximal to the major histocompatibility complex region on chromosome six. We propose naming this motif the "RING finger" and it is found in 27 proteins, all of which have putative DNA binding functions. We have synthesized a peptide corresponding to the RING1 motif and examined a number of properties, including metal and DNA binding. We provide evidence to support the suggestion that the RING finger motif is the DNA binding domain of this newly defined family of proteins.

Amino Acid Sequence↗

Biodegradable microparticles for oral immunization.

Ovalbumin (OVA) was entrapped in poly(lactide-co-glycolide) microparticles and administered to mice. Following intraperitoneal immunization, the microparticles induced both proliferative T-cell responses and cytotoxic T-cell responses in spleen cells. Following oral immunization, the mean salivary IgA antibody response to microparticles was significantly greater than the response to soluble OVA (p < 0.0001). Serum IgG antibody levels were also significantly greater in the group administered microparticles (p < 0.001). Cholera toxin B subunit was also entrapped in microparticles. Following oral immunization in mice, specific antibody-secreting cells were detected both in the spleens and in the mesenteric lymph nodes.

Administration, Oral↗

Enhanced secretory IgA and systemic IgG antibody responses after oral immunization with biodegradable microparticles containing antigen.

Intragastric immunization may lead to the induction of antibodies in the secretory immune system including saliva. The antibody response is usually short-lived. The objectives of this study were to see whether oral immunization with biodegradable microparticles containing antigen might lead to enhanced mucosal responses. Ovalbumin (OVA) was entrapped in a novel antigen delivery system comprising poly (D,L-lactide-co-glycolide) (PLGA) microparticles. Salivary IgA and serum IgG responses after three daily oral immunizations in BALB/c mice were assayed by ELISA at weekly intervals and compared with those to soluble antigen. Low levels of salivary IgA antibodies were detected at Weeks 2 and 3 in both groups and no significant differences were found. After a secondary series of intragastric immunizations at Week 4, marked differences were apparent between the groups. The mean salivary IgA titre at Week 6 was 959 +/- 494 U compared with 30 +/- 5 in the soluble OVA group (P less than 0.0001). Significant differences were still apparent at Weeks 7-8 through the value was falling. Serum IgG antibodies were detectable and were significantly greater in the particle group (at Weeks 4 and 8) than in controls (P less than 0.001). These results suggest that microparticles are taken up by antigen-presenting cells in Peyer's patches, then slowly degrade in vivo and release entrapped antigens, and thus can function as potent antigen delivery systems giving rise to both mucosal and systemic responses. Microparticles have considerable potential as a controlled released antigen delivery system for the induction of longer-term immune responses at mucosal surfaces.

Administration, Oral↗

Purification and characterization of biologically active scatter factor from ras-transformed NIH 3T3 conditioned medium.

Scatter factor (SF), a glycoprotein produced by cultured fibroblasts, acts in vitro on epithelial cells causing separation and increased local motility. In this study, the polypeptide was purified to apparent homogeneity in high yields with conserved biological activity from medium conditioned by ras-transformed NIH 3T3 cells, by a three-step procedure involving ammonium sulphate fractionation, cation-exchange and hydroxyapatite chromatography. After purification, SF specific activity increased from approximately 0.3 units/microgram in unprocessed conditioned medium to approximately 5 units/ng, and cumulative recovery of biological activity was approximately 38%. Treatment of pure SF with N-glycanase resulted in a decreased Mr, but no concomitant effect was observed on biological activity. Proteolytic activity was absent from samples of both partially purified and pure SF. Our biochemical studies showed that SF, which is highly aggregated in low-ionic-strength media, is not aggregated in 0.4 M-salt. Under non-reducing conditions, pure SF migrated as a single stained band at Mr 67,000 on SDS/PAGE, and biological activity was eluted from unstained gels with an identical Mr. SF was electrofocused sharply at pI 8.5 with no degradation of activity. From ultracentrifugation studies (under non-aggregating conditions), the sedimentation coefficient of active SF was 3.7 S and f.p.l.c. molecular sieve chromatography indicated a Stokes' radius of 2.95 nm. The calculated Mr from these data was 61,400. The appearance of three stained polypeptides of Mr 82,000, 57,000 and 32,000 derived from the Mr-67,000 constituent after reduction with mercaptoethanol suggests that SF may be a heterodimer of Mr-57,000 and -32,000 subunits. Data from protein sequence analysis of the hydroxyapatite-purified protein confirms that SF has sequence identity with both rat hepatocyte growth factor and human fibroblast tumour cytotoxic factor.

Amidohydrolases↗

Biodegradable microparticles as controlled release antigen delivery systems.

A model but poor immunogen, ovalbumin (OVA), was entrapped in a novel antigen delivery system comprising poly (D,L-lactide-co-glycolide) (PLGA) microparticles. Both the primary and the secondary IgG antibody responses obtained with OVA in microparticles were compared to those obtained with OVA emulsified in Freunds' adjuvants by two routes of immunization, intraperitoneal (i.p.) and subcutaneous (s.c.) injection. Following single i.p. or s.c. injections, the IgG serum antibody responses to OVA in microparticles were significantly greater than the responses to OVA in Freunds' complete adjuvant (FCA) for up to 10 weeks. After s.c. booster doses of OVA, the secondary IgG antibody responses to OVA in microparticles remained greater than the secondary responses to OVA in Freunds', but not significantly so. Furthermore, the primary IgG responses to OVA in microparticles obtained 8-12 weeks after a single i.p. injection were greater than the secondary responses to OVA in Freunds' obtained by repeat s.c. injections at Weeks 0 and 6. These results demonstrate that microparticles can function as potent antigen delivery systems for an entrapped antigen. Due to their ability to degrade slowly in vivo and to release entrapped antigens, microparticles have considerable potential as controlled release antigen delivery systems for the induction of long-term immune responses.

Animals↗

Gangliocytic paraganglioma in association with a duodenal diverticulum.

Gangliocytic paraganglioma is an extremely rare benign neurogenic tumor nearly exclusively located in the second portion of the duodenum, also the most common site of duodenal diverticula. A case is reported of a gangliocytic paraganglioma presenting in a 65-yr-old woman with a 1-yr history of postprandial cramping abdominal pain culminating in a single episode of melena leading to laparotomy. The tumor was identified with difficulty by endoscopy following negative barium studies. Histologically, the tumor is composed of carcinoid-like cells admixed with varying numbers of ganglion cells in a substratum of neuroid spindle cells. The epithelioid cells contain argyrophilic cytoplasmic granules confirmed by electron microscopy to be dense core membrane-bound secretory granules. Review of the literature suggests the tumor described is typical both clinically and pathologically of gangliocytic paraganglioma of the duodenum, except for its unprecedented occurrence in association with a duodenal diverticulum.

Aged↗

Activation of liver macrophages in murine malaria is enhanced by vaccination.

During blood-stage infection of mice with a lethal variant of Plasmodium yoelii, cells in both spleen and liver became activated to reach a peak at day 5. In mice protected by vaccination, activation was accelerated after infection. The most striking difference observed was in the 10-fold greater yield of infiltrating cells, including macrophages, obtained from the liver just before the mice recovered. Their capacity to give an oxidative burst and their cytotoxic activity against tumour cells was also more than 10 times normal. This suggests that the recruitment of inflammatory cells to the liver plays an important role in the protection of vaccinated mice against malaria.

Animals↗

Epithelioma cuniculatum: verrucous carcinoma of the foot.

A patient with epithelioma cuniculatum, an unusual, highly keratinizing squamous cell neoplasm of the foot with locally aggressive behavior, is presented herein. Review of the literature reveals several similar cases that are reported under the names of epithelioma cuniculatum, papillomatosis cutis carcinoides, and verrucous carcinoma of the skin. The relationship of this neoplasm to other forms of verrucous carcinoma is noted. Lack of metastatic involvement indicates that a conservative surgical approach should be used, when possible, in the therapeutic management of this lesion.

Carcinoma, Papillary↗

Consanguinity analysis in Israeli mental retardates.

Consanguinity rates were analyzed in 904 families of retardates studied in 11 Israeli Jewish ethnic groups. It was estimated that the representative recessive gene frequency is .00518, implying that a gene equilibrium maintained by mutation alone is improbable and that some other hypothesis should be considered. The proportions of homozygotes among the following idiopathic subgroups are estimated as follows: 18%-19% homozygotes among severe idiopathic retardates with nonconsanguineous parents and no affected siblings; 74%-76% homozygotes among severe idiopathic retardates with first-cousin parents and no affected siblings; 5% homozygotes among mild idiopathic and idiopathic-familial retardates with nonconsanguineous parents; and 41% homozygotes among mild idiopathic and idiopathic-familial retardates with first-cousin parents. The estimated number of major gene loci within ethnic groups is 17-21 for severe idiopathic retardation and 43-61 for mild idiopathic retardation. These findings provide a basis for genetic counseling of families with single retardates of unknown cause. They can also be useful in epidemiologic studies of nongenetic factors. The great prevalence of common gene defects causing retardation, coupled with the rarity of disorders of amino acid metabolism in the same series, seem to indicate that further emphasis on amino acid metabolism may be nonproductive in the scientific study of retardation and that other biochemical approaches should be encouraged.

Amino Acid Metabolism, Inborn Errors↗