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Biomedical subjects

A Alam

Publications and source records attributed to A Alam.

At least 55 records · Page 3Linked to original sources
PubMed1998

Band ligation vs endoscopic sclerotherapy in esophageal varices: a prospective randomized comparison.

OBJECTIVE: A prospective randomized trial was conducted to compare efficacy, safety and complications of band ligation (BL) with sclerotherapy (Scl). METHODS: Patients with esophageal variceal bleeding were randomized into two study groups. BL (group A) was done in 28 patients whereas 30 patients (group B) had Scl. After initial treatment, follow-up sessions were repeated by the same method every two weeks till obliteration or reduction to grade 1. Subsequent sessions of endoscopy were done every three months, same procedure was repeated for recurrence of varices and for any episode of rebleeding. RESULTS: Initial control of bleeding by Scl was achieved in 22 of 28 patients (78%) and in 23 of 24 patients (96%) with BL. Eradication of varices was significantly better achieved in BL group, with less treatment sessions required in Group A as compared with group B 2 +/- 1.2 vs 5 +/- 2.5, P < 0.001). Major complications (3% vs 16%, P < 0.05) as well as mortality (11% vs 21%, P > 0.05) was higher in group B. CONCLUSION: Band ligation was more effective mode of treatment and was associated with lesser early mortality and complications as compared with sclerotherapy.

Endoscopy↗
PubMed1998

Hiatal hernia in achalasia.

Barium esophagograms of 89 patients out of 110 with manometrically proven achalasia were reviewed. Only four (4.4%) patients showed association of hiatal hernia, indicative of its rare occurrence. Presence of hiatal hernia, is said to have less likelihood of associated achalasia but this association does exist as per our report and that of others.

Adult↗
PubMed1998

Hepatocellular carcinoma: analysis of 76 cases.

Hepatocellular carcinoma is one of the most common malignancies world wide. We present data on 76 patients admitted to the Shaikh Zayed Hospital. Mean age was 52.2 +/- 11.3 years. Eighty six percent were males and 14% females. Eighty-six percent patients had underlying cirrhosis documented on ultrasound examination. Seventy-five percent were positive for anti HCV, 10% for HBsAg positive, 10% for both HBsAg and anti HCV and 5% cases had negative viral serology. Main clinical features were abdominal pain, weight loss, jaundice, hepatomegaly and ascites. Forty-three percent patients were Child-Pugh class A, 30% class B and 13% class C and 14% were non cirrhotic. Mean alfa fetoprotein levels were 142 +/- 155 ng/ml (range 2.7 to 1470). Diagnosis of hepatocellular carcinoma was established in 60 patients by fine needle aspiration biopsy under ultrasound guidance. Two patients died after biopsy due to uncontrollable bleeding. Fifty-four percent patients had a solitary lesion and 46% had multifocal or diffuse lesions. The average size of lesion was 7.8 x 8.1 cm. Twenty-two patients received intralesional alcohol injection. Fifty-four percent of these with a tumor size greater than 8 cm died during follow up. The major cause of death was liver failure in 8 patients and fatal bleeding occurred in 4 patients. Hepatocellular carcinoma has a high prevalence in middle aged males with a strong association with anti HCV positive cirrhosis. Patients with a tumour size greater than 8 cm have a poor response to intralesional alcohol injection.

Abdominal Pain↗
PubMed1997

Specific activation of the cysteine protease CPP32 during the negative selection of T cells in the thymus.

Cysteine proteases of the CED-3 and ICE family have been recently proposed as the ultimate executioners in several mammalian cell death pathways. Among them, the cysteine protease CPP32 has been shown to participate in programmed cell death (PCD), or apoptosis, affecting lymphoid cells in vitro. In the thymus, negative selection is a mechanism through which developing thymocytes expressing a TcR with high affinity for self peptide-MHC complexes are eliminated by PCD. In order to investigate the role of CPP32 in thymic apoptosis, isolated thymocytes were submitted to cell surface CD3 crosslinking by immobilized anti-CD3 mAb or to dexamethasone treatment. Although apoptosis occurred in the absence or after crosslinking with anti-CD3 mAb, specific activation of CPP32, as assessed by the extent of proteolytic cleavage of the p32 zymogen, was only detected in thymocytes cultured in the presence of the immobilized antibody or dexamethasone. This activation was a very early event during apoptosis as it occurred before the exposure of phosphatidyl serine to the upper side of the cell membrane. This was observed both in anti-CD3- and dexamethasone-induced apoptosis. Moreover, using mice transgenic for pigeon cytochrome C (PCC)-specific TcR, we were able to show that, after injection of PCC, the activation of CPP32 and cleavage of its substrate occurred in thymocytes obtained from mice expressing a permissive MHC haplotype for PCC presentation (H-2k). Moreover, PCC induced apoptosis was blocked by the caspase inhibitor zVAD. While spontaneous apoptosis was not accompanied by detectable levels of CPP32 processing, it was characterized by the proteolysis of poly(ADP-ribose) polymerase (PARP) and was blocked by the cysteine protease inhibitor, zVAD-CH2F. Taken together, these results support the concept that CPP32 is among the earliest effectors of the pathway leading to negative selection of autoreactive thymocytes. Our results also suggest the involvement of a distinct CPP32-like cysteine protease in spontaneous apoptosis of thymocytes.

Animals↗
PubMed1997

The large subunit of replication factor C is a substrate for caspase-3 in vitro and is cleaved by a caspase-3-like protease during Fas-mediated apoptosis.

Caspase-3 is an ICE-like protease activated during apoptosis induced by different stimuli. Poly(ADP-ribose) polymerase (PARP), the first characterized substrate of caspase-3, shares a region of homology with the large subunit of Replication Factor C (RF-C), a five-subunit complex that is part of the processive eukaryotic DNA polymerase holoenzymes. Caspase-3 cleaves PARP at a DEVD-G motif present in the 140 kDa subunit of RF-C (RFC140) and evolutionarily conserved. We show that cleavage of RFC140 during Fas-mediated apoptosis in Jurkat cells and lymphocytes results in generation of multiple fragments. Cleavage is inhibited by the caspase-3-like protease inhibitor Ac-DEVD-CHO but not the caspase-1/ICE-type protease inhibitor Ac-YVAD-CHO. In addition, recombinant caspase-3 cleaves RFC140 in vitro at least at three different sites in the C-terminal half of the protein. Using amino-terminal microsequencing of radioactive fragments, we identified three sites: DEVD723G, DLVD922S and IETD1117A. We did not detect cleavage of small subunits of RF-C of 36, 37, 38 and 40 kDa by recombinant caspase-3 or by apoptotic Jurkat cell lysates. Cleavage of RFC140 during apoptosis inactivates its function in DNA replication and generates truncated forms that further inhibit DNA replication. These results identify RFC140 as a critical target for caspase-3-like proteases and suggest that caspases could mediate cell cycle arrest.

Apoptosis↗
PubMed1996

Persistence of dominant T cell clones in synovial tissues during rheumatoid arthritis.

In a previous study, we showed that the T cell repertoire is biased in the synovial membrane (SM) compared with peripheral blood during rheumatoid arthritis (RA). The same bias was observed in different joints from the same patient and seems to be the same over time. To discover whether this bias was due to expansion of a clonal subset resulting from activation by conventional Ag(s) or to polygonal stimulation by superantigen(s), we sequenced more than 650 TCRBV-D-J junctional regions from freshly isolated SM and peripheral blood of two DR4-RA patients. From each patient, two SM were obtained on the same day, and a third was obtained later. Several dominant clones were found in SM but not in peripheral blood. Some of them were found only at the first time point in anatomically different SM, the majority persisted over time, and others were detected only at the second time point. Analysis of the complementarity-determining region 3 (CDR3) showed a bias in TCRBD and amino acid usage. Valine, encoded by randomly inserted N nucleotides, was used by 45% of dominant clones compared with 18% in the control population (p less than 0.001). In addition, GXXG and TSG motifs were frequently observed in the CDR3 of these dominant clones. These data indicate a dynamic TCR selection process during the perpetuation phase of RA. The dynamic changes of dominant clones also suggest a determinant spreading mechanism during RA.

Amino Acid Sequence↗
PubMed1995

T-cell receptor variable region of the beta-chain gene use in peripheral blood and multiple synovial membranes during rheumatoid arthritis.

In order to look for a site-specific T-cell response in RA SM, PCR analyses using oligonucleotide primers specific for 24 TCRBV (V beta) families were performed to compare the respective usage of each TCRBV gene by T cells present in PB and SM of 13 patients with RA. In four patients, SM cells from two or three sites of inflammation were subjected to analysis. In one patient, synovial tissue was studied at two different phases of the disease, resulting in a total number of 19 samples of SM cells, which were compared with paired samples of PB cells. The results showed that whereas all 24 TCRBV gene families could be detected in both PB and SM cells, there was some skewing of increased or decreased usage frequencies of particular TCR V beta genes among SM cells. Three TCRBV families were often overexpressed in SM: V beta 3, V beta 17, and V beta 22. Moreover, V beta 4 was often decreased in SM (7 out of 13). This decrease was statistically significant in the RA population studied. SM from different joints of a given patient showed similar variations of T-cell repertoire compared to PB, even 6 months later in the course of the disease. These results demonstrate a biased TCRBV gene utilization in RA SM. This bias appears to be similar in different joints and at different times in the course of the disease. No correlation was found between the bias of TCR repertoire in SM and the HLA typing of these patients.

Adult↗
PubMed1995

2-Mercaptopropionylglycine affords enhanced radioprotection after a liposome encapsulation.

Use of radioprotective drugs in radiotherapy is desirable to protect normal tissues. 2-mercaptopropionylglycine (MPG) has shown promising results in experimental radioprotection. In this report, a liposome drug delivery system for MPG has been used in Swiss albino mice exposed to 1 to 8 Gy whole body Gamma-irradiation to test whether or not this modality enhances the MPG afforded radioprotection. A statistically significant, dose dependent enhancement of protection by liposome encapsulated MPG (LEM) was observed. LEM, as compared to free MPG, improved the viabilities of spleen and bone marrow cells by factors between 1.11 and 2.23 for different doses of radiation.

Animals↗
PubMed1994

Distribution of cytokine proteins within epiretinal membranes in proliferative vitreoretinopathy.

This study reports on the immunohistochemical staining for cytokine proteins of 26 epiretinal membranes obtained from eyes undergoing surgery for the treatment of proliferative vitreoretinopathy. All specimens were investigated for the distribution of staining for interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF alpha), interferon-gamma (IFN gamma) and interleukin-2 (IL-2). The results showed that 22 of the membranes (85%) stained for TNF alpha not only intracellularly but also in the extracellular matrix. This contrasts with the findings that only 2 membranes stained for IL-1 alpha and that another 3 were positive for IL-1 beta. Staining for the cytokines IL-6 and IFN gamma was also observed in 9 and 7 membranes respectively. None of the specimens investigated stained with antibodies to IL-2 or control antibodies, and none of three normal retinas stained with any of the antibodies used. Pre-absorption of anti-cytokine antibodies with the corresponding human recombinant cytokines abolished staining of cells and extracellular matrix. The present findings support growing evidence that cytokine-mediated pathways of inflammation are involved in the pathogenesis of proliferative vitreoretinopathy, and draw attention to the possibility that interaction between extracellular matrix-bound cytokine and inflammatory leucocytes or resident cells of the retina may promote the development and perpetuation of this condition.

Antibodies, Monoclonal↗
PubMed1993

Clonality of T lymphocytes expanded with IL-2 from rheumatoid arthritis peripheral blood, synovial fluid and synovial membrane.

The association of rheumatoid arthritis (RA) with particular MHC class II genes suggests that autoantigen-specific T cell clones present in joints could be central to the pathogenesis of the disease. Previous investigations on the clonal diversity of T cells infiltrating the rheumatoid synovial membrane have yielded conflicting results. With the use of Southern blot analysis, we investigated the clonality of rheumatoid T cell lines expanded from peripheral blood, synovial fluid and synovial tissue. From peripheral blood lymphocyte (PBL) of RA patients and healthy normal controls, we also checked the consequences of two different culture conditions on the clonality of these cell lines. From control PBL, we found that in vitro non-specific expansion of non-clonal T cell populations does not create artefactual clonal selection. However, growing T cells in vitro with IL-2 seems to be able to lead to preferential expansion of cells bearing IL-2 receptor (IL-2R). We identified such in vivo activated IL-2-sensitive T cell clones frequently in RA synovial tissue (8/13) and more rarely in synovial fluid and peripheral blood (3/12). One patient presents the same T cell receptor gene rearrangements in synovial membrane of two affected joints. In RA synovial tissue, the frequency of these IL-2-responsive T cells is most prevalent among actively inflamed membranes removed early in the disease process. The role and the relevance to the disease of these IL-2-responsive T cells remain to be elucidated.

Adult↗
PubMed1993

Changing survival and impairment rates at 18-24 months in outborn very low-birth-weight infants: 1984-1987 versus 1980-1983.

Outcomes at 18-24 months corrected age of very low-birth-weight infants admitted to our Neonatal Intensive Care Unit in 1984-1987 (period 2) were compared with the outcomes of infants admitted in 1980-1983 (period 1) (total 1357 infants). In the 500-750-g birth-weight subgroup, the survival rate increased from 32 to 54% (p = 0.002). Rates of moderate and severe impairment at 18-24 months (neurosensory deficit, or Bayley corrected mental developmental index < or = 68) in this subgroup decreased from 41 to 15% (p = 0.005), and in those without severe impairment, mean mental Bayley scores in periods 1 and 2 were 84 +/- 18 and 90 +/- 16, respectively (p = 0.20). Analysis after exclusion of small-for-gestational-age infants gave similar results. In the small-for-gestational-age infants of birth weight 500-750 g, the survival rate increased but the impairment rate was unchanged between periods. It is concluded that outcomes improved in 1984-1987 compared with 1980-1983 only for infants with birth weight of 500-750 g.

Birth Weight↗
PubMed1993

Suggested reference ranges in clinical chemistry for apparently healthy males and females of Pakistan.

Seven hundred and eighty six apparently healthy males (418) and females (368) aged 0-69 years were randomly selected for estimation of reference ranges of 24 serum analytes at the clinical chemistry laboratory of The Aga Khan University Hospital (AKUH). Of the total study samples, 56% (439/786) were in the paediatric age group (0-14 years) and 44% (347/786) in the adult (15 > or = 60 years) group. Beckman Astra Ideal Autoanalyzer was used for all the estimations. Mean and standard deviations (SD) were calculated for each of the age groups. Reference ranges were calculated following standard methods of the International Federation of Clinical Chemistry (IFCC) and International Committee for Standardization in Haematology (ICSH).

Adolescent↗
PubMed1992

Design of liposome to improve encapsulation efficiency of gelonin and its effect on immunoreactivity and ribosome inactivating property.

Gelonin, purified from the seeds of Gelonium multiflorum, using cation-exchange and gel-filtration chromatography was characterised for its purity, homogeneity and molecular weight by reverse-phase HPLC (RP-HPLC) and SDS-PAGE analysis. The HPLC purified gelonin was used for entrapment studies in the liposomes. Liposomes were prepared by reverse phase evaporation (REV) technique using three different types of lipid composition in the same molar ratio. The method resulted in 75-80% entrapment efficiency of gelonin in the liposomes. Entrapped and unentrapped gelonin was characterized for physico-chemical, immunochemical and biological properties. The immunoreactivity of entrapped gelonin was fully preserved but the ribosome-inactivating property was slightly inhibited. The method involved mild conditions, highly reproducible and the liposomes produced appeared to be stable for several months. It has important implications in the development of cell type specific cytotoxic agents where a chemical cross-linking is involved which significantly inhibits both immunoreactivity and ribosome-inactivating ability of the toxin.

Cell-Free System↗