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Biomedical subjects

M Iqbal

Publications and source records attributed to M Iqbal.

At least 109 records · Page 6Linked to original sources

Coordination of copperpolyamine complex with imidazoles potentiates it superoxide dismutase mimicking activity and abolishes its interaction with albumin.

Mixed ligand complexes of copper polyamine with biomolecules such as imidazole, substituted imidazoles or pyridine have been synthesized and characterized. These molecules were used because of their low toxicity and high activity. These complexes were found to possess a distorted octahedral microenvironment with a potential SOD mimicking activity. The IC50 values for these complexes were of the order of 2-90 microM. Pyridine and imidazole complexes were most effective as they possess the lowest IC50 values of 2.1 and 6 microM respectively which are higher than the IC50 value of polyamine copper complex. Based on the uric acid estimations, it has also been ascertained that these complexes dismute O2- without inhibiting xanthine oxidase activity. The presence of increasing concentrations of albumin had no effect on the SOD mimicking activity of mixed ligand complexes. Polyamine complex, however lost approximately 80% of SOD mimicking activity in the presence of albumin (1 mg). These results suggest that coordination of polyamine copper complex with imidazoles/pyridine may abolish their binding affinity for albumin while potentiating their SOD mimicking activity.

Albumins↗

Porphyrin-mediated photosensitization has a weak tumor promoting activity in mouse skin: possible role of in situ-generated reactive oxygen species.

Reactive oxygen species (ROS) have been implicated in skin tumor promotion. Earlier, we showed that porphyrin-mediated cutaneous photosensitization results in the in situ generation of ROS. Recently, we have provided the first in situ evidence for the involvement of ROS in stage I tumor promotion. In this study we further show that in situ-generated ROS act as weak complete tumor promoters in 7,12-dimethylbenz[a]anthracene (DMBA)-initiated mouse skin. Papillomas were induced in Swiss albino mice by a single topical application of DMBA as initiator. The promotion was achieved in these mice by the sustained generation of ROS through dihematoporphyrin ether (DHE)-mediated cutaneous photosensitization, which was done once every day (six times a week) for 24 weeks. The first appearance of visible papillomas could be recorded 24 weeks after the initiation. The highest tumor incidence of 60% occurred at a dose of 2.5 mg/kg body wt DHE. Increasing the dose of DHE produced a decrease in the incidence as well as in the number of papillomas. In contrast, the number of carcinomas/mouse increased with increasing dose of DHE. Histopathology of the tumor samples indicated the formation of in situ carcinoma also in skin. ROS generated through DHE-mediated photosensitization resulted in a approximately 3 fold induction of ODC activity 9 h after photosensitization. DHE-mediated photosensitization enhanced [3H]thymidine incorporation in cutaneous DNA in a dose-dependent manner. A maximum 5-fold induction of [3H]thymidine incorporation was observed at a dose of 10 mg/kg body wt DHE. The longer latency period, low incidence of tumor induction, low tumor yield and low induction of ODC activity as compared with TPA represent the weak but complete tumor promoting potential of in situ-generated ROS. The low tumor incidence and tumor yield observed at higher doses of DHE may be due to the ablation of tumors at early stages due to the strong photodynamic action of DHE.Our data indicate that porphyrin-mediated photosensitization has a weak tumor promoting effect in mouse skin and in situ-generated ROS may play an important role in the development of this response.

9,10-Dimethyl-1,2-benzanthracene↗

Activation of the protease from human adenovirus type 2 is accompanied by a conformational change that is dependent on cysteine-104.

Adenovirus codes for a protease the activity of which can be regulated in vitro by an 11 residue peptide (GVQSLKRRRCF) derived from another viral protein, pVI. Three cysteine residues, one in the activating peptide and two in the protease (C104 and C122), play a central role in both activation and catalysis. Expression of protease mutants in insect cells has shown that C104 is not essential for proteolytic activity. GVQSLKRRRCF also caused a concentration-dependent increase in tryptophan fluorescence of protease expressed in Escherichia coli that paralleled the increase in proteolytic activity, indicating that activation was accompanied by a conformational change. Tryptophan fluorescence of C104S was not increased by the addition of GVQSLKRRRCF, nor was the fluorescence of wild-type protease increased by the addition of the peptide analogues where cysteine is replaced by aspartic acid or serine, suggesting that C104 is involved in activation and C122 in catalysis.

Adenoviruses, Human↗

Screening actinomycetes for extracellular peroxidase activity.

A diverse collection of actinomycete strains were screened for production of extracellular peroxidase activity by adapting a chemiluminescence analysis system developed for horseradish peroxidase-based enzyme-linked immunosorbent assay. Extracellular peroxidase activity was found to be common but quantitatively variable, and this rapid and sensitive screening system permitted identification of a small group of high-producing strains. A range of spectrophotometric assays were compared for the measurement of peroxidase activity in concentrated culture supernatants of two selected thermophilic streptomycetes. Of these, the peroxide-dependent oxidation of 2,4-dichlorophenol was identified as the most robust and reproducible assay for quantitative studies.

Journal Article↗

Thyroid dysfunction in HIV-infected children: is L-thyroxine therapy beneficial?

PURPOSE: To assess thyroid function in symptomatic HIV-infected infants and children with failure to thrive and to evaluate clinical response in patients with hyperthyrotropinemia to levothyroxine. METHODS: We evaluated 11 children (mean age: 1.5 years; males = 5, females = 6) with HIV infection and failure to thrive (weight and height > 2 SD below the mean) for presence of hypothyroidism. Thyroid-stimulating hormone (TSH) and thyroxine (T4) were measured. Four children with high basal TSH and one child with a normal basal TSH underwent the Thyrotropin-releasing hormone (TRH) stimulation test as well. Four children received treatment with L-thyroxine. RESULTS: Eight of the 11 children had high basal TSH levels. All patients had normal or increased T4 values. The TRH stimulation test showed an exaggerated response in all four patients with high basal TSH values and a normal response in one patient with normal basal THS values. All four patients who received treatment with L-thyroxine showed normalization of the TSH. Increased growth velocity was noted in 3 of 4 patients. The fourth patient died within two weeks following initiation of therapy for overwhelming candida sepsis. The autopsy of this patient showed atrophy of the thyroid gland. Two of the four patients with high TSH levels, who did not receive L-thyroxine, died; the other two did not show any improvement in their height z scores. Two patients with a high TSH also had high thyroid-binding hormone (TBG) levels. Both patients with the high TBG died within 2 to 3 months of the study. CONCLUSIONS: Hypothyroidism as indicated by elevated basal TSH and abnormal TRH response was common in the HIV-infected children in this study and may have contributed to failure of growth in these children. Replacement therapy resulted in correction of abnormal TSH and improvement of height z scores during the period of observation. The significance of these findings needs to be confirmed in a larger prospective study.

Child, Preschool↗

Prevalence of sand fly fever, West Nile, Crimean-Congo hemorrhagic fever, and leptospirosis antibodies in Pakistani military personnel.

To determine the prevalence of antibodies to viral diseases known or suspected to be present in Pakistan, we studied 570 sera from three groups of adults; two of the groups were involved in outbreaks of hepatitis, and the third included men admitted to a hospital for evaluation of febrile illnesses. Immunoglobulin G antileptospiral antibody was found in 1 to 6% of the subjects, with the highest rate in enlisted military personnel hospitalized for febrile illness. One man in the group with febrile illness had significantly elevated immunoglobulin M antileptospiral antibody titers. However, in a group of recruits experiencing suspected non-A, non-B hepatitis, 19 (11%) of 173 had a 4-fold rise in immunoglobulin M antibody to leptospirosis. Antibody to sand fly fever viruses was found in 27 to 70%. Antibody to West Nile virus was present in 33 to 41% of subjects. Antibody reactive with Japanese encephalitis virus was present in 25%, but plaque reduction neutralization tests suggested this to be cross-reaction with West Nile virus. All 212 specimens tested for antibody to Crimean-Congo hemorrhagic fever and Hantaan viruses were negative. This study indicates that diseases known to be prevalent in other areas of southwest Asia and the Middle East are also prevalent in northern Pakistan and may impact on those traveling or working in this area.

Adolescent↗

Laparoscopic liver biopsy to evaluate hepatic dysfunction in patients with hematologic malignancies: a useful tool to effect changes in management.

Hepatic dysfunction is common in patients who receive intensive chemotherapy and it is important to determine the etiology in order to institute appropriate therapy. The role of laparoscopic liver biopsy in patients with neutropenia, thrombocytopenia, or both was evaluated as a mean of making treatment decisions and as a determinant of clinical outcome. Laparoscopic liver biopsy was performed in 29 subjects who were receiving intensive cytotoxic therapy with or without bone marrow transplantation. One to three direct-vision laparoscopic liver biopsies were performed in each patient using a Tru-cut needle during general anesthesia. Platelet concentrate transfusions were usually given before, during, and immediately after biopsy. Bleeding was controlled with spatula electrocautery. Thirty-two biopsies were obtained in 29 patients. At the time of liver biopsy, white blood cell and platelet counts ranged from 0 to 14,300/microliters (median: 2500/microliters), and 1000 to 47,000/microliters (median: 20,000/microliters), respectively. Bleeding at the liver biopsy site was readily controlled during the procedure without clinical evidence of significant bleeding; no procedure-related complications were noted and no patients required re-exploration. All biopsies were informative and the lesions observed in 32 biopsies revealed graft-versus-host disease (n = 5), hepatic candidiasis (n =1), hepatic veno-occlusive disease (n = 3), cholestasis (n = 19), hemosiderosis (n = 26), toxic injury (n = 8), hepatic steatosis (n = 4), granuloma (n = 1), viral infection (n =1), and malignancy (n = 1). Laparoscopic liver biopsy has been proven to be an effective means of assessing the cause of liver dysfunction in patients who were thrombocytopenic and immunosuppressed. The diagnosis obtained at laparoscopic liver biopsy altered therapy in nine of 29 (31%) patients.

Adult↗

Novel dipeptide aldehydes are proteasome inhibitors and block the MHC-I antigen-processing pathway.

Class I MHC (MHC-I) molecules present peptides derived from Ag that are processed in the cytosol. The proteasome is a multicatalytic protease complex that is present in the cytosol and has been implicated in cytosolic Ag processing. Novel dipeptide aldehydes were designed, synthesized, and demonstrated to specifically inhibit the chymotrypsin-like protease activity of isolated proteasomes, but produced relatively little inhibition of cathepsin B, a vacuolar cysteine protease. The inhibitors were membrane permeable and inhibited intracellular cleavage of a membrane-permeable fluorogenic substrate of the chymotrypsin-like proteasome activity. When a model Ag, OVA, was introduced into the cytoplasm of M12.B6 murine B cells by electroporation, the proteasome inhibitors blocked its processing for subsequent presentation by MHC-I molecules. The inhibitors had little effect on class II MHC processing of exogenous Ag. The potencies of different inhibitors for blockade of MHC-I Ag processing correlated directly with their potencies for inhibition of the chymotrypsin-like proteasome activity. In contrast, conventional inhibitors of vacuolar cysteine proteases (e.g., leupeptin and benzyloxycarbonyl-Phe-Ala-CHN2) had little effect on MHC-I processing or the chymotryspin-like activity of isolated proteasomes. These results directly demonstrate that inhibition of proteasome activity blocks MHC-I Ag processing, confirming a role for proteasomes in this pathway. Moreover, they suggest that the chymotrypsin-like activity of the proteasome may be of major importance to the cytosolic processing of at least some Ag.

Aldehydes↗

Ferric nitrilotriacetate (Fe-NTA) is a potent hepatic tumor promoter and acts through the generation of oxidative stress.

Fe-NTA is a known renal carcinogen. However, little is known about its carcinogenic potential in liver. In this study we for the first time show that Fe-NTA is a potent hepatic tumor promoter. Fe-NTA administration induced dose dependently the hepatic ornithine decarboxylase (ODC) activity several folds as compared to its activity in the saline-treated rats. Similarly, hepatic DNA synthesis which is measured as [3H]thymidine incorporation in DNA is also increased following Fe-NTA treatment. The effects of Fe-NTA were similar to other tumor promoters not only with respect to inducing ODC activity and [3H]thymidine incorporation in DNA but also in depleting antioxidant armory of the tissue. Fe-NTA depleted levels of glutathione to about 35% of the saline-treated control and activities of antioxidant enzymes catalase, glutathione peroxidase, glutathione reductase and glucose 6-phosphate dehydrogenase decreased significantly (45-55% of saline-treated control). Concomitant with the depletion in antioxidant armory, Fe-NTA augmented hepatic microsomal lipid peroxidation more than three folds. The pretreatment of rats with antioxidants BHA or BHT diminished the observed effects of Fe-NTA. Our data indicate that Fe-NTA is a potent hepatic tumor promoter and acts through a mechanism involving oxidative stress.

Animals↗

Crude extracts of hepatoprotective plants, Solanum nigrum and Cichorium intybus inhibit free radical-mediated DNA damage.

The presence of plant extracts of Solanum nigrum and Cichorium intybus in the reaction mixture containing calf thymus DNA and free radical generating system protect DNA against oxidative damage to its deoxyribose sugar moiety. The effect was dependent on the concentration of plant extracts. However, the effect of Cichorium intybus was much pronounced as compared to the effect of Solanum nigrum. These studies suggest that the observed hepatoprotective effect of these crude plant extracts may be due to their ability to suppress the oxidative degradation of DNA in the tissue debris.

Acetates↗

Characterization and sequence analysis of a Streptomyces rochei A2 endoglucanase-encoding gene.

A 7-kb fragment of Streptomyces rochei A2 chromosomal DNA was cloned into pAT153 and shown to confer endoglucanase (EglS) activity on Escherichia coli cells. In E. coli clones, the EglS was secreted into the periplasm. Deletion analysis revealed that an 827-bp fragment was enough for the enzymatic activity. Sequence analysis showed that the 827-bp fragment codes for the catalytic domain of the enzyme. The complete sequence of the gene (eglS) is 1149-bp long. A signal peptide, a catalytic domain and a cellulose-binding domain were identified from the nucleotide sequence, and the EglS found to belong to the family H of cellulase catalytic domains. These conclusions were substantiated by determination of the N-terminal sequence of the purified protein and zymogram analysis, which revealed protein species with a molecular mass equal to that deduced from the nt sequence analysis.

Amino Acid Sequence↗

[Clinical and radiological results of distal radius fractures].

We report retrospective analysis of results of conservative and operative methods of distal radial fractures, which was carried out to control our treatment methods. Three hundred and ninety-three patients were treated from 1. 7. 1991 to 1. 7. 1992, 361 (91.9%) were followed up to 14 months with average age of 60.1 years (16 to 92 years). Three hundred and twenty-seven patients (90.6%) were treated by conservative methods, 9 (2.5%) by percutaneous pinning, 21 (5.8%) by transfixation through bases of metacarpal bones and 4 (1.1%) by ventral supporting plates. Clinical examination showed 69.6% good, 24.9% fair and 5.5% poor results. Radiological results according to AO-scheme were compared with clinical results, and 70% clinical results correlated with radiological results. Our results show that comminuted and displaced intraarticular fractures AO-classification C 2, C 3 are indications of transfixation and A 3 and some exceptional cases of C 1 are indications of percutaneous pinning.

Adolescent↗

Cathepsin G: localization in human cerebral cortex and generation of amyloidogenic fragments from the beta-amyloid precursor protein.

Amyloid deposits in Alzheimer's disease, Down's syndrome and aged brain are composed largely of A beta protein, which is generated by proteolytic processing of beta-amyloid precursor protein. Proteases responsible for liberating the A beta protein from the precursor have not yet been identified. Here, we examined the ability of cathepsin G, a chymotrypsin-like protease, to cleave two protease substrates: (i) a fluorogenic hexapeptide, whose sequence spans the cleavage site in the precursor for generating the A beta NH2-terminus, and (ii) recombinant human beta-amyloid precursor protein purified from a baculovirus expression system. Unlike two other members of the chymotrypsin family, cathepsin G readily degraded the hexapeptide. Furthermore, cathepsin G cleaved the beta-amyloid precursor protein to generate several breakdown products, including a prominent 11,500 mol. wt fragment immunoreactive with antibodies directed against the COOH-terminus of the protein. This COOH-terminal fragment co-migrated using two-dimensional isoelectric focusing/sodium dodecyl sulfate-polyacrylamide gel electrophoresis with C-100, a recombinant COOH-terminal segment of the beta-amyloid precursor, whose NH2-terminus is one residue upstream of the NH2-terminus of the A beta domain. We also examined the localization of cathepsin G in human brain. The distribution of cathepsin G-containing cells was examined by immunohistochemistry in the temporal cortex of both Alzheimer's and aged control samples. Cathepsin G-like immunoreactivity was contained specifically within neutrophils. As visualized by double-labeling with antibodies to cathepsin G and Factor VIII, neutrophils were most frequently found within meningeal or cortical blood vessels. In addition, occasional neutrophils could be identified without an apparent vascular surround, in the brain parenchyma. By simultaneous labeling with antibodies to cathepsin G and A beta protein, neutrophils were also sometimes found associated with both parenchymal and vessel amyloid deposits; however, these associations were rare. These findings indicate that cathepsin G is capable of cleaving the beta-amyloid precursor protein to liberate the free NH2-terminus of the A beta protein and may have access to areas where this material is deposited in Alzheimer's disease. However, since there is no physical association between neutrophils and deposited amyloid and no increase in the number of neutrophils in an Alzheimer's brain, cathepsin G seems to be an unlikely mediator of amyloid deposition in this disease.

Alzheimer Disease↗

Epidemic hepatitis E in Pakistan: patterns of serologic response and evidence that antibody to hepatitis E virus protects against disease.

IgM and IgG anti-hepatitis E virus (HEV) patterns were determined in sera collected during a hepatitis outbreak in Pakistan. HEV infection was detected serologically in 122 patients. IgM anti-HEV was detected in specimens collected up to 2 weeks before and 5-7 weeks after hospitalization in 91% and 100%, respectively, of 122 HEV-infected patients. IgG followed a similar pattern. Peak antibody titers appeared 2-4 weeks after hospitalization. At 20 months after hospitalization, IgM anti-HEV was not detected in any of 33 patients; IgG was found in all. IgG anti-HEV appeared to be protective in contracts of patients. This study confirms HEV as the cause of the outbreak, quantifies IgM and IgG anti-HEV responses, provides evidence that IgG anti-HEV protects against hepatitis E, and demonstrates that IgG anti-HEV persists, but at diminished titer, after infection. Hepatitis E in young adults is the result of primary infection with HEV and, if reinfection occurs, it does not commonly cause serious illness.

Antibodies, Viral↗

Vegetable sponge as a matrix to immobilize micro-organisms: a trial study for hyphal fungi, yeast and bacteria.

The vegetable sponge of Luffa cylindrica was studied as a matrix for the immobilization of hyphal fungi, yeast and bacteria. All were observed to be entrapped within the sponge. When the various immobilized systems were subcultured in their respective fresh nutrient media, the hyphal fungi showed an increase in biomass with no cellular release and secondary colony formation. The immobilized yeast and bacteria released cells into the medium. Advantages of the reticulated biostructure as an immobilization matrix are discussed.

Bacteria↗

Nerve injuries associated with supracondylar fracture of the humerus in children.

Vascular complications associated with supracondylar fracture of humerus are well recognised. Less well recognised are neurological injuries associated with this fracture. A prospective study was conducted to explore the role of open reduction and internal fixation of this fracture. The article presents the incidence of nerve lesions in 46 cases of supracondylar fracture of humerus; review of pertinent literature is also included.

Child↗