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Biomedical subjects

A Rehman

Publications and source records attributed to A Rehman.

At least 37 records · Page 2Linked to original sources
PubMed2000

Multiple lethal effects induced by a benzimidazole anthelmintic in the anterior intestine of the nematode Haemonchus contortus.

A mechanism of benzimidazole efficacy against parasitic nematodes is postulated to involve inhibition of intestinal secretory vesicle transport via depolymerization of microtubules. We show that fenbendazole (FBZ) treatment of lambs causes pathology localized to the anterior intestine in the parasitic nematode Haemonchus contortus. The pathology included gross disintegration of the anterior intestine, DNA fragmentation in anterior intestinal nuclei with characteristics of an apoptosis-like process, and inhibition of host erythrocyte digestion. These lethal effects were associated with inhibited transport of apical secretory vesicles in the anterior intestine, and then generalized dispersal of these vesicles contents throughout the intestinal cytoplasm and worm body. Cytoplasmic accumulation of secretory vesicles and undigested erythrocytes preceded DNA fragmentation and vesicle content dispersal. Both DNA fragmentation and vesicle content dispersal were detected in disintegrated intestine and intestine that had not yet undergone disintegration. These pathologic effects in the anterior intestine appear sufficient to explain the efficacy of FBZ against adult H. contortus. The results implicate mechanisms in the anterior intestine that govern dispersal of apical secretory vesicle contents, DNA fragmentation and tissue disintegration as effectors of this pathology.

Animals↗
PubMed2000

Effect of dichromate on population and growth of various protozoa isolated from industrial effluents.

Three protozoa belonging to genera Euglena, Vorticella and Stylonychia collected from industrial wastes were cultured in a medium containing inorganic salts, basically meant for the growth of algae. Protozoa showed rapid growth in the medium. Hexavalent chromium (K2Cr2O7) at a concentration of 5 micrograms/L in the medium adversely affected the growth of protozoa. At the end of eight days of Cr administration, the population of Euglena, Vorticella and Stylonychia increased 8-, 4.5- and 10-fold, respectively, as against 30-, 6.75- and 50-fold increase in the control cultures. No apparent death phase and no change in activity or morphology of protozoa was observed at this Cr concentration. The protozoa were also exposed to different metal ions, viz. Pb (2.42 mmol/L), Cr (0.48 mmol/L), Cd (0.36 mmol/L), administered in the culture medium for a period of 2 years. The metal tolerance for S. mytilus and V. microstoma was Pb > Cr > Cd. E. proxima could not tolerate any of the long-term metal treatments. Because of the ability of these protozoa to tolerate high concentrations of heavy metals, their potential role in remediation of heavy metals from industrial wastewater is considered.

Animals↗
PubMed2000

The steady-state levels of oxidative DNA damage and of lipid peroxidation (F2-isoprostanes) are not correlated in healthy human subjects.

Oxidative damage to DNA in human tissues can be determined by measuring multiple products of oxidative damage to the purine and pyrimidine bases using gas chromatography-mass spectrometry (GC-MS). Oxidative damage to lipids (lipid peroxidation) can be quantitated by the mass spectrometry-based determination of F2-isoprostanes, specific end-products of the peroxidation of arachidonic acid residues in lipids. For both DNA base damage products and 8-epi prostaglandin F2alpha (PGF2alpha), there is a wide variation in levels between different healthy human subjects. We measured multiple products of oxidative damage to DNA bases in white cells, and 8-epi PGF2alpha in plasma, from blood samples obtained from healthy human subjects in the UK and in Portugal. No correlation of 8-epi PGF2alpha levels with levels of any modified DNA base (including 8-hydroxyguanine) was observed. We conclude that no single parameter can be measured as an index of "oxidative stress" or "oxidative damage" in vivo.

Adult↗
PubMed1999

Tomato consumption modulates oxidative DNA damage in humans.

Consumption of a single serving of tomatoes by healthy human volunteers was sufficient to alter levels of oxidative DNA base damage in white cell DNA within 24 h. Levels of the mutagenic oxidized purine base 8-hydroxyguanine decreased, especially in those subjects whose initial levels of this base were higher than the mean. However, total DNA base damage remained unchanged since levels of 8-hydroxyadenine rose. The ability of tomato consumption to modulate oxidative DNA damage in the short term may indicate why daily consumption of fruits and vegetables is beneficial in decreasing cancer incidence.

DNA↗
PubMed1999

Defined characteristics of cathepsin B-like proteins from nematodes: inferred functional diversity and phylogenetic relationships.

Numerous cathepsin B-like protein sequences (CBLs) have been reported from nematodes. However, the relationships among these proteins remain unclear. Here, expression of several CBL transcripts in the gut of the parasitic nematode Haemonchus contortus was demonstrated. To assess potential functional diversity, multiple nematode CBL sequences were compared with known functional domains of cathepsin B. These domains included the occluding loop, S2' and S2 subsites, and the pro region. Four groups of CBLs were defined based on variable characteristics in the occluding loop region, which incorporates a portion of the S2' subsite. Further diversity was observed in amino acids expected to contribute to the S2 subsite. In addition, short signature sequences near the cysteinyl active site region characterized known CBLs of parasites from the orders Strongylida and Rhabditida. The criteria established were used to identify two predicted CBLs from parasitic (Ascaris suum) and free-living (Caenorhabditis elegans) nematodes as potential orthologues, and provided a basis to evaluate orthologue status of other CBLs. Variability in the domains analyzed suggests substantial functional diversity in enzymatic properties of nematode CBLs. Results suggest that the selective amplification and evolution of distinct CBL lineages has contributed to differences in CBLs among species and groups of nematodes. Nutrient digestion is one potential factor promoting CBL diversification in these organisms.

Amino Acid Sequence↗
PubMed1999

Increased oxidative damage to all DNA bases in patients with type II diabetes mellitus.

Gas chromatography-mass spectrometry was used to measure the oxidative DNA damage in diabetic subjects and controls. Levels of multiple DNA base oxidation products, but not DNA base de-amination or chlorination products, were found to be elevated in white blood cell DNA from patients with type II diabetes as compared with age-matched controls. The chemical pattern of base damage is characteristic of that caused by an attack on DNA by hydroxyl radical. An increased formation of the highly reactive hydroxyl radical could account for many of the reports of oxidative stress in diabetic subjects. There was no evidence of an increased DNA damage by reactive nitrogen or chlorine species.

Base Pairing↗
PubMed1999

Ifosfamide and vinorelbine in metastatic breast cancer in patients with prior anthracycline therapy.

OBJECTIVE: A prospective trial to evaluate the efficacy and toxicity of ifosfamide (IFX) and vinorelbine (VNB) in patients with prior anthracycline therapy for metastatic breast cancer (MBC) was conducted. At the same time, the scheduling of VNB in order to minimize toxicity of the combination was also evaluated. PATIENTS AND METHODS: Twenty-three patients with MBC who had already received initial chemotherapy with doxorubicin-containing regimens either as adjuvant or as first-line treatment in MBC were entered into the study. IFX 3 g/m(2) and mesna 3 g/m(2) were given in divided doses over 2 days. In 4 patients, VNB was given 25 g/m(2) on days 1 and 3 in 3-h infusion. In 8 patients, VNB was given on days 1 and 8 and in 5 patients VNB was given on days 1 and 15. Thirteen patients had received doxorubicin in adjuvant setting, while 10 patients received doxorubicin as first-line treatment in metastatic disease. Dominant disease sites were soft tissues in 7 patients, visceral in 12 patients, and bone in 4 patients. The median age was 47 years. RESULTS: Overall objective response was seen in 12/23 patients (52.2%). Four patients achieved complete remission (CR), 8 patients achieved partial remission (PR). The median duration of response was 9 months in responding patients, and the median overall survival duration was 15 months. The major dose-limiting toxicities were neutropenia grade III and IV in 8/17 patients and asthenia grade III and IV in 4 patients. CONCLUSION: IFX and VNB is an active combination. Neutropenia and asthenia were most significant when VNB was given on days 1 and 3. In the best-tolerated regimen, VNB was given on days 1 and 8.

Adult↗
PubMed1999

Non-Hodgkin's lymphoma in Pakistan: a clinicopathological profile of 175 patients.

OBJECTIVE: Non-Hodgkin's Lymphomas (NHL) are common in Southeast Asia, Middle East and Africa. The study was primarily undertaken to establish the demographic and clinicopathologic features of NHL in Pakistan. A secondary aim was to determine the applicability of the International Prognostic Index (IPI) developed by the international lymphoma task force in a developing country. METHODS: A retrospective and prospective analysis was performed on 175 patients over 14 years age who presented to the Department of Oncology between August 1994 and December 1996. All patients underwent initial staging according to Ann Arbor Staging System. Histopathologic classification was done according to the International Working Formulation. The IPI was applied to patients with aggressive lymphomas and age adjusted index to patients < 60 years, complete remission (CR), disease free survival (DFS) and overall survival (OS) were calculated. RESULTS: All 175 patients were evaluable. Median age of our patients was 45 years. Male to female ratio was 1.9:1. Seventeen (9.7%) patients were classified as low grade lymphomas while 158 (91.3%) had intermediate and high grade NHL. Large cell lymphoma was present in 30.9% patients. CHOP (cyclophosphamide 650 mg/m2 day 1, vincristine 1.4 mg/m2 day 1, doxorubicin--45 mg/m2 day 1 and prednisone 100 mg/m2 day 1-5) was the most common chemotherapy regimen used. Advanced stage (74.9%) > B symptoms (51%) and extranodal involvement (74.3%) were present. One hundred sixty-seven patients were evaluable for response of which 42.8% achieved CR. Median DFS was 19 months and median OS was 22 months. The IPI was applicable to 153 patients and age adjusted IPI to 124 of 153 patients. CONCLUSION: Aggressive histology, extranodal diseases, B symptoms and advanced disease are common. International index and age adjusted international index predicted outcome accurately in various risk groups.

Adolescent↗
PubMed1999

Enteral access procedures revisited in the era of minimally invasive surgery.

The impact of adequate nutrition on wound healing, immunity and patient morbidity has been ap preciated since the early work of Stanley Dudrik in the late 60s and early 70s. Although total parenteral nutrition improved the outcome in nutritionally debilitated patients, it often led to overwhelming infections in these immunologically sensitive patients. In the 90s, the importance of gut as an endocrine and immune organ has been well established, as weU as the superiority of enteral feeding over parenteral nutrition, in most cases. Here we discuss the available techniques for accessing the gastrointestinal tract as well as the guidelines for selection of patients.

Journal Article↗
PubMed1998

A tissue specific approach for analysis of membrane and secreted protein antigens from Haemonchus contortus gut and its application to diverse nematode species.

General methods to conduct tissue specific analysis are largely lacking for nematodes. An approach is described that focused on isolation of membrane and secreted protein genes from the gut of the parasitic nematode Haemonchus contortus. The approach capitalized on a monoclonal antibody that recognizes multiple membrane and secreted worm proteins. Polyclonal antisera made against these proteins were used to screen expression cDNA libraries made either from adult worm gut or whole worm. The genes identified encode predicted or known membrane and secreted proteins from gut, including a cysteine protease, a zinc metallopeptidase and a previously described GA1 protein. Another gene, Hc40, was isolated from the whole worm cDNA library and is nearly identical to a vaccine patent sequence pBTA879. Tissue analysis demonstrated the intended focus on membrane and secreted proteins from parasite gut was achieved. Proteins related to each of those described were identified from other nematode species through data base analysis. Additionally, this analysis led to (1) identification of homologues of each gene in C. elegans; (2) deduction of a dimorphic structure in the Hc40 protein; (3) recognition of both monomorphic and dimorphic families of Hc40-related proteins; and (4) detection of two apparent classes of transcripts (mep1a and mep1b) that would each encode a divergent version of the putative zinc metallopeptidase MEP1. The tissue specific approach and information base described should generally contribute to investigations on nutrient digestion and related secretory processes in nematode gut.

Amino Acid Sequence↗
PubMed1998

The effects of iron and vitamin C co-supplementation on oxidative damage to DNA in healthy volunteers.

The effects of co-supplementing healthy volunteers with iron (14 mg/day ferrous sulphate) and vitamin C (either 60 mg/day or 260 mg/day as ascorbic acid) on levels of oxidative DNA damage in white blood cells were studied. The subjects were divided into two groups: one group of 20 volunteers with a higher mean initial level of plasma vitamin C (71.9 +/- 14.0 mumol/l) and a second group of 18 volunteers with a lower mean level (50.4 +/- 25.8 mumol/l). In the first group there was a significant rise in several oxidative DNA base damage products and in total oxidative DNA damage in DNA extracted from white blood cells, but not in 8-hydroxyguanine, after 6 weeks of supplementation. However, after 12 weeks levels returned approximately to normal. In the group with the lower initial level of plasma ascorbate, presupplemental levels of oxidative DNA damage were higher and decreased on supplementation with iron and ascorbate. Since oxidative DNA damage has been suggested as a risk factor for the development of cancer, the implications of increased levels in well-nourished subjects after iron/ascorbate supplementation are disturbing in view of the frequent use of dietary supplements containing both iron salts and ascorbate.

Adult↗
PubMed1998

Necrotizing fasciitis following gall-bladder perforation.

Necrotizing fasciitis continues to carry a very high mortality and prolonged morbidity. Gallstones have previously not been reported as a cause of this condition. We report a patient who presented with gallbladder perforation leading to necrotizing fasciitis of the anterior abdominal wall. The only organism isolated was Escherichia Coli, cultured from necrotic issue.

Abdominal Muscles↗
PubMed1997

Blood pressure changes during transient myocardial ischemia: insights into mechanisms.

OBJECTIVES: We investigated the contribution of changes in systemic blood pressure to the genesis of spontaneous myocardial ischemia. BACKGROUND: Although increases in heart rate often precede the development of spontaneous myocardial ischemia, it remains a subject of controversy whether these are accompanied by simultaneous changes in blood pressure. METHODS: Using an ambulatory monitoring device that triggered blood pressure recordings from the level of the ST segment, we documented systolic and diastolic blood pressure and heart rate changes related to episodes of ST segment depression in 17 patients with stable coronary artery disease. RESULTS: Systolic blood pressure and heart rate, but not diastolic pressure, increased significantly before the onset of ST segment depression and persisted throughout the ischemic episode. There was a significant correlation between the changes in heart rate and systolic blood pressure during episodes of myocardial ischemia (r = 0.5, p = 0.0005) and between heart rate and systolic blood pressure changes at 1-mm ST segment depression during treadmill exercise testing and ambulatory monitoring (r = 0.73, p = 0.0005 for heart rate; r = 0.77, p = 0.0008 for systolic blood pressure), indicating that patients with a low heart rate threshold during ischemic episodes also had a lower systolic blood pressure threshold before ischemia during both tests. Circadian changes in systolic blood pressure paralleled the variations in heart rate and ischemic episodes, with the lowest values at night. CONCLUSIONS: Significant increases in myocardial oxygen demand, including systolic blood pressure, occur during episodes of spontaneous myocardial ischemia. Patients with a lower heart rate threshold during ischemic episodes had a lower systolic blood pressure threshold during both ambulatory monitoring and treadmill exercise. The effects of antianginal therapy on blood pressure changes during ischemia need to be explored further.

Aged↗
PubMed1997

Serine319 and 321 are functional in isocitrate lyase from Escherichia coli.

With site-directed mutagenesis, Ser319 and Ser321 in conserved stretch 3 of tetrameric isocitrate lyase from Escherichiacoli were each substituted with alanine, cysteine, asparagine, or threonine in addition to simultaneous alanine/alanine substitutions. Besides their absolute conservation in all aligned isocitrate lyase sequences, the location of these serine residues, which flank a completely conserved proline, had been suggested in the active site in previous research by studies of photoinactivation of the enzyme by vanadate [Ko et al. (1992) J Biol Chem 267:91]. All substitutions for Ser321 and 319 except by threonine appreciably reduced the kcat of E. coli isocitrate lyase relative to that for wild-type (100) as follows: S319A, 0.4; S319C, 0.05; S319N, 0.01; S319T, 32.3; S321A, 2.9; S321C, 0.3; S321N, 0.1; S321T, 0.3; and S319A/S321A, 0, with little or no effect on the Km for the substrate Mg2+-Ds-isocitrate. The most active variant S319T exhibited threefold less activity than the wild-type enzyme; all variants assembled into tetramers. The S319T mutant isocitrate lyase was 100-fold more active than the S321T variant. This observation suggests that the requirement for a beta-hydroxymethyl group of serine in catalysis is less important at position 319 than at position 321. Although most singly substituted variants had very low isocitrate lyase activity, all variants harboring mutant isocitrate lyase of very low activity did grow on acetate asa sole carbon source albeit with longer doubling times and lag phases. Substitution of Pro320 by Ala, Asp, Gly, or His was highly detrimental to activity and increased the Km for substrate 3.5- to 8-fold; this suggests that Pro fixes the location of adjacent Ser OH groups and facilitates substrate binding and catalysis. From these collective results, it is proposed that Ser319 and Ser321 are involved in E.coli isocitrate lyase catalysis, perhaps by stabilizing the postulated reaction intermediate succinate trianion in the aci-carboxylate form and the related transition state via hydrogen bonding.

Alanine↗
PubMed1997

Lysine 194 is functional in isocitrate lyase from Escherichia coli.

Lysine 194 in conserved stretch 1 of tetrameric isocitrate lyase from Escherichia coli has been replaced by using the restriction-enzyme-site elimination method of directed mutagenesis. Expression of subunits of each variant and of wild-type (wt) enzyme was equivalent and all variants assembled into tetrameric proteins. The variants K194R and K194H had kcat values relative to that of wt enzyme taken as 100 of 11 and 7, respectively. Km values for Mg2+-Ds-isocitrate (in mM units) were: 0.13 for wt-enzyme; 0.12 for the K194R variant; and 0.55 for the K194H variant. Substitution at position 194 of Leu or Glu resulted in zero catalytic activity. These results establish that Lys 194 is another functional residue in conserved stretch one of isocitrate lyase from E. coli besides H184, K193, C195, and H197. Because K194 can be specifically replaced by the basic residues His and Arg with resultant lowered activity and by His with an increased Km value, it may contribute to a cation center and facilitate substrate binding as well as orientation of the developing transition state.

Escherichia coli↗