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Biomedical subjects

J Iqbal

Publications and source records attributed to J Iqbal.

At least 91 records · Page 5Linked to original sources

Utilization of scalp hair for evaluating epilepsy in male and female groups of the Pakistan population.

Concentrations of Fe, Cu, Zn, Cr, Mg and Ca are determined in scalp hair of adult epileptic and normal male and female subjects by atomic absorption spectroscopy. A total of 85 hair samples for normal male/female subjects and 78 of male/female epileptic subjects were analyzed within the respective age groups of 28 to 30 and 24 to 27 years. The study showed higher average concentration of Zn, Fe and Cu in normal male subjects compared with the epileptic subjects. Levels of Ca, Mg and Cr were lower in normal male adults than those found in epileptic subjects. Epileptic females showed higher average concentrations of Zn, Ca and Cu. The correlation coefficient study indicated significant correlation (r > 0.589 at P = 0.001) between Fe and Cr, Mg, Ca and Cu for epileptic females only. For normal male subjects Ca showed a strong correlation for Zn and Fe and for Cr and Ca. The regression analysis showed the significant role of Zn, Ca, Mg and Cr in scalp hair of normal and epileptic subjects. Accordingly, the metal-to-metal ratio analysis revealed critical Mg/Zn ratios as indicators of healthy (< 1) and epileptic (> 1) subjects. The ratio data are used for evaluation of the status of epileptic patients based on their ailment history.

Adult↗

Cytoadherence-related homologous motifs in Plasmodium falciparum antigen Pf155/RESA and erythrocyte band 3 protein.

Cytoadherence of Plasmodium falciparum-infected erythrocytes plays an important role in the pathogenesis of cerebral malaria. The identity of cell surface molecules on parasitized erythrocytes involved in cytoadherence is of great interest to understand the molecular basis of this mechanism. Peptide sequences derived from exofacial loops of the erythrocyte antigen band 3 from parasitized erythrocytes have previously been shown to inhibit cytoadherence. We now report that a non-repeated region of Pf155/RESA (residues 213-218) contains a hexapeptide motif being highly homologous to cytoadherence inhibitory sequences from band 3. Synthetic peptides containing the hexapeptide motif of Pf155/RESA inhibited the binding of P. falciparum-infected erythrocytes to melanoma cells in vitro. Furthermore, individuals residing in malaria-endemic areas have antibodies reactive with epitopes involving these motifs in band 3 and in Pf155/RESA.

Amino Acid Sequence↗

Immunogens containing sequences from antigen Pf332 induce Plasmodium falciparum-reactive antibodies which inhibit parasite growth but not cytoadherence.

Immunogens based upon sequences from the P. falciparum asexual blood stage antigen Pf332 were assessed for their capacity to induce antibodies inhibiting parasite growth or cytoadherence of infected erythrocytes in vitro. Selection of the Pf332 sequences was based on their reactivity with the human monoclonal antibody (MoAb) 33G2 which inhibits parasite growth as well as cytoadherence in vitro. Octameric multiple antigen peptides (MAP) were assembled based upon either a trimer of the minimal epitope recognized by the MoAb, VTEEI, or a Pf332 sequence including that motif, SVTEEIAEEDK. A dimer of SVTEEIAEEDK was also expressed in Escherichia coli, genetically fused to ZZ, two IgG-binding domains of staphylococcal protein A. Rabbit antibodies elicited by the immunogens reacted with Pf332 in immunofluorescence and in ELISA with Pf332 peptides which were also recognized by MoAb 33G2. The MAP with branched (VTEEI)3 peptide induced the highest titres of P. falciparum-reactive antibodies. In contrast to MoAB 33G2, none of the polyclonal Pf332 reactive sera cross-reacted with repeat sequences of the malaria antigen Pf155/RESA. The polyclonal Pf332-reactive antibodies inhibited parasite growth efficiently but had no or very low inhibitory effect in a cytoadherence assay. Thus, while Pf332 may be an important target for parasite neutralizing antibodies its involvement in cytoadherence is unclear.

Amino Acid Sequence↗

Vitamin D deficiency rickets in breast-fed infants presenting with hypocalcaemic seizures.

At the Aga Khan Hospital (AKUH), 65 infants presented with hypocalcaemic seizures, subsequently found to have rickets. Forty-six infants less than 6 months were totally or predominantly breast fed. In a subgroup of 15 mothers and their infants, we found very low plasma levels of 25(OH) vitamin D of < 5 micrograms/l and 7.5 +/- 3.3 micrograms/l, respectively. Neither mothers nor infants received vitamin D supplementation. Maternal vitamin D deficiency and non-supplementation in the infants were the likely causes of rickets in our patients. Prophylactic vitamin D 400 i.u. administered to infants up to 2 years and 800 i.u. to women in pregnancy and during lactation is recommended to prevent vitamin D deficiency.

Breast Feeding↗

Carboxyterminal propeptide of type I procollagen in osteomalacia.

Carboxyterminal propeptide of type I procollagen (PICP) was measured in sera from 25 patients with osteomalacia due to privational vitamin D deficiency. The mean value of serum PICP was significantly raised in patients with osteomalacia compared with 40 normal subjects (mean +/- SD, 161 +/- 82 ng/ml and 113 +/- 31 ng/ml, respectively; P = 0.01). The raised serum PICP reflected the accelerated bone turnover in this condition as did the elevated serum total alkaline phosphatase (ALP), but the variation in values of serum PICP noted in individual patients may reflect the different stages of osteomalacia. The normalization of serum PICP and ALP, indicating a healing process of the bone disorder, needed longer time of vitamin D and calcium therapy. In contrast, adjusted serum calcium and inorganic phosphate (IP) responded and normalized rapidly. Serum PICP and total ALP appeared to behave differently in the disease and in its response to vitamin D therapy suggesting that these two markers may represent different functions of osteoblasts in osteomalacia.

Adult↗

Disagreement between the Roche Cobas Core and Hybritech TANDEM-E PSA assays when measuring free, complexed and total serum prostate specific antigen.

A comparison of the Roche Cobas Core and Hybritech TANDEM-E PSA (prostate specific antigen) assays revealed a large difference in the reactivity of each assay to the separated free and complexed forms of serum PSA in patients with prostatic carcinoma. The Roche assay was relatively much more responsive to the free form, but the Hybritech assay was relatively more responsive to the complexed form and total serum PSA. It is possible that the adoption of a universal standard for PSA will not completely resolve the disagreement between PSA assay on individual patient samples, and the use of separate assays for the free and complexed forms may be necessary for the further clinical development of PSA as a tumour marker.

Biomarkers, Tumor↗

Humoral immune responses to Plasmodium falciparum antigens in children and adults living in a hypoendemic area of Punjab (Pakistan).

We have investigated the prevalence and the levels of antibodies reactive with repeat sequences in Plasmodium falciparum asexual blood-stage Pf155/ring-infected erythrocyte surface antigen (RESA), Pf332 antigen, and the circumsporozoite (CS) protein in 532 children and adults residing in a hypoendemic area in the Punjab (Pakistan). We show here that the levels of antibodies reactive with synthetic peptides corresponding to repeat sequences in these antigens increased gradually with age. However, the prevalence and levels of antibodies reactive with the peptides were quite low as compared with the high prevalence of such antibodies in donors from areas holoendemic and hyperendemic for malaria. The levels of Ag332 (2-12)2-reactive antibodies in individual sera as well as in the study population as a whole correlated well with the levels of antibodies to the Pf155/RESA peptide (EENV)6. However, there was no correlation between anti-(EENV)6 and anti-Ag332 (2-12)2 antibody levels and malaria parasitemia. There was a significant negative correlation between anti-(NANP)6-reactive antibodies and the parasite rate, suggesting that a heavy load of blood-stage parasites may be one factor that exerts an immunosuppressive effect on the antibody response to the sporozoites.

Adult↗

Sero-diagnosis for viral hepatitis in 93 patients admitted with acute hepatitis in three different teaching hospitals in Lahore.

Serodiagnosis was done in 93 patients admitted with acute viral hepatitis (AVH) to three teaching hospitals in Lahore. Five (5.4%) had hepatitis A, 39 (41.9%) hepatitis B (2 of these were anti delta positive) [see erratum notice], 44 (47.3%) probable hepatitis E and 3(3.2%) had HAV/HBV co-infection. Antibody to hepatitis C (anti HCV) was detected in 6 patients (6.4%); 2 with HBV and 4 with probable HEV infection. Excluding 39 patients with hepatitis B and 3 with HBV as part of co-infection, there was evidence of previous HBV infection in 39 out of the remaining 51 patients. In the subset of 6 children, 3 had hepatitis A and 3 hepatitis E. Of these, 5 had evidence of previous exposure to HBV and one was also positive for anti HCV. Our results are suggestive of a strong background of HBV infection raising concern about its chronic sequelae in the community.

Acute Disease↗

Pattern of renal disease in children.

In 1992 a total of 1298 patients with renal diseases were seen in the medical outpatients department. Eight hundred and forty-seven (65.2%) had urinary tract infection and 265 (20.5%) had nephrotic syndrome. Two hundred and twenty patients required inpatient care, which constituted 3.3% of total number of patients admitted to medical wards. Sixty-four (29%) of admitted patients with renal disease had nephrotic syndrome, 29 (13.1%) had acute renal failure due to various causes including haemolytic uraemic syndrome. The average stay was 5.8 days per patient and mean bed occupancy was 3.4 beds per day. Various renal diseases in children together form an important group of disorders often requiring long term care and this should be taken into account when planning provision of child health services particularly at tertiary care level.

Age Factors↗

Plasmodium falciparum: analysis of the cytoadherence inhibition of the human monoclonal antibody 33G2 and of antibodies reactive with antigen Pf332.

The capacity of a human monoclonal antibody (MAb 33G2) to interfere in vitro both with Plasmodium falciparum merozoite invasion and cytoadherence of infected erythrocytes to melanoma cells has been reported. MAb 33G2 cross-reacts with several P. falciparum antigens but shows highest reactivity with repeated sequences in the asexual blood stage antigen Pf332. This study was conducted in order to further analyze the cytoadherence inhibition mediated by MAb 33G2 and to evaluate the relative contribution of antibodies to Pf332 in the inhibitory activity of immunoglobulins from P. falciparum immune donors. We show here that MAb 33G2 inhibits cytoadherence of infected erythrocytes (PRBCs) with similar efficiency independently of the strain of parasite, while the inhibitory capacity of immunoglobulin fractions from Liberian immune donors was restricted to some strains only. There appears to be no correlation between the reactivity with Pf332 of immunoglobulin preparations from different donors and their capacity to inhibit cytoadherence of PRBCs to melanoma cells. In contrast to MAb 33G2, polyclonal antibodies affinity purified on the Pf332 peptide containing the epitope seen by the MAb showed little or no inhibition of cytoadherence of infected erythrocytes.

Amino Acid Sequence↗

Seroreactivity with the Plasmodium falciparum blood stage antigen Pf332 in adults and children from malaria-endemic regions.

It has earlier been reported that the human monoclonal antibody (MoAb 33G2) and polyclonal antibodies reactive with Pf332 may interfere in vitro with the erythrocytic cycle of Plasmodium falciparum at two potential target sites for protective antibodies, indicating that the antigen may constitute an important target for immune responses during malaria infections. MoAb 33G2 shows its highest reactivity with repeated sequences in the antigen Pf332 and also cross-reacts with determinants in Pf155/RESA. This study was conducted in order to assess the prevalence of seroreactivity against Pf332 in individuals residing in areas of different malaria endemicity, and in children with different degrees of disease severity. We now report that individuals resident in malaria-endemic regions show a high prevalence of seroreactivity to antigen Pf332 repeat sequences. The mean antibody concentrations were significantly higher in donors from Liberia, Madagascar and Gambia compared with Thai and Colombian donors, probably reflecting the higher degree of exposure in the African regions. Although the levels of such antibodies in individual sera correlated well with the levels of antibodies to one Pf155/RESA repeat peptide, only a minor part of the peptide-reactive antibodies were cross-reactive between the two antigens. In Gambian children, the mean concentrations of antibodies reactive with Pf332 or Pf155/RESA peptides were significantly higher in children with severe than with mild malaria. Further longitudinal studies are needed to evaluate the capacity of Pf332 to induce potentially protective or harmful antibody responses.

Adult↗

Epitope specificity and capacity to inhibit parasite growth in vitro of human antibodies to repeat sequences of the Plasmodium falciparum antigen Ag332.

It has earlier been shown that the Plasmodium falciparum-reactive human monoclonal antibody 33G2 inhibits parasite growth in vitro as well as cytoadherence of infected red blood cells to melanoma cells in vitro. MoAb 33G2 recognizes an epitope of the P. falciparum antigen Ag332 and cross-reactive determinants in Pf155/RESA and Pf11.1 located in repetitive regions containing sequences of regularly spaced pairs of glutamic acid. To study whether antibodies of this specificity frequently occur in human immune sera and if they could be of importance for protective immunity, antibodies were affinity purified on MoAb 33G2 reactive Ag332 peptides. The epitope specificity of the affinity purified antibodies, determined by the Pepscan method, resembled that of MoAb 33G2, but showed differences in fine specificity. The antibodies cross-reacted to some extent with Pf11.1 and Pf155/RESA repeat peptides as detected by peptide ELISA and Pepscan. In indirect immunofluorescence all purified antibodies displayed a dotted pattern of staining of late stage infected red blood cells of two lines of the P. falciparum strain FCR3, including a Pf155/RESA deficient line. The in vitro growth of these two lines was efficiently inhibited by the affinity purified antibodies, indicating that their inhibitory effect was mainly due to reactivity with antigens other than Pf155/RESA. This, and the fact that Pf11.1 has been shown not to be expressed by the asexual stages suggests that Ag332 may be an important target for potentially protective antibodies in vivo and that Ag332 based immunogens are of interest for development of malaria subunit vaccines.

Amino Acid Sequence↗

Severe malaria in Gambian children is not due to lack of previous exposure to malaria.

The reasons why only a small proportion of African children infected with Plasmodium falciparum develop severe or fatal malaria are not known. One possible reason is that children who develop severe disease have had less previous exposure to malaria infection, and hence have less acquired immunity, than children who develop a mild clinical attack. To investigate this possibility we have measured titres of a wide range of anti-P. falciparum antibodies in plasma samples obtained from children with severe malaria, children with mild malaria and from children with other illnesses. Mean antibody levels in patients with malaria were higher than those in patients with other conditions but, with only one exception, there were no significant differences in antibody titres between cases of severe or mild malaria. A parasitized-erythrocyte agglutination assay was used to estimate the diversity of parasite isolates to which children had been exposed; plasma samples obtained from children with cerebral malaria recognized as many isolates as did samples obtained from children with mild disease. Our findings do not provide any support for the view that the development of severe malaria in a small proportion of African children infected with P. falciparum is due to lack of previous exposure to the infection.

Animals↗

Gastric carcinoma--a study of 100 cases in northern Pakistan.

We describe 100 consecutive patients with histologically proven gastric carcinoma who were admitted to various hospitals in Northern Pakistan. Twenty-six per cent of patients were under 40 years of age. In a majority of patients the tumour was of a morphological type associated with poor prognosis. In most cases the disease was already at an advanced stage at the time of diagnosis, and most patients died within one year.

Adenocarcinoma↗

Evaluation of the hypoglycaemic effect of Achyranthes aspera in normal and alloxan-diabetic rabbits.

Blood glucose levels of normal and alloxan diabetic rabbits were determined after oral administration of various doses of Achyranthes aspera powdered whole plant and certain aqueous and methanolic extracts. Oral administration of 2, 3 and 4 g/kg of A. aspera powder produced a significant dose-related hypoglycaemic effect in normal as well as in diabetic rabbits. The water and methanol extracts also decreased blood glucose levels in normal and alloxan diabetic rabbits. A 7-day acute toxicity study in rabbits did not reveal any adverse or side effects of this folk medicine at dosages up to 8 g/kg orally. It is possible that the plant could act by providing certain necessary elements like calcium, zinc, magnesium, manganese and copper to the beta-cells.

Administration, Oral↗