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Biomedical subjects

J Iqbal

Publications and source records attributed to J Iqbal.

At least 19 recordsLinked to original sources

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

Use of cyanide and diethyldithiocarbamate in the assay of superoxide dismutases.

Eucaryotes have two major forms of superoxide dismutase (SOD), Cu,ZnSOD and MnSOD; in most tissues Cu,ZnSOD is present in higher amounts than MnSOD. To assay MnSOD, Cu,ZnSOD can be inhibited selectively by millimolar concentrations of cyanide ion. However, calculation of MnSOD activity from the differential cyanide inhibition assay is complex and small experimental errors can cause large errors in the calculated MnSOD activity. We have assessed how interaction of cyanide and hydrogen peroxide with cytochrome c can lead to further errors in the xanthine oxidase-cytochrome c assay for SOD. Alternatively, Cu,ZnSOD can be completely inactivated by 50 mM diethyldithiocarbamate (DDC) at 30 degrees C for 1 h without affecting the activity of MnSOD. Since DDC reduces cytochrome c, the treated samples must be thoroughly dialyzed or desalted before assay. In the case of lung homogenates, dialysis is not an extra step since fresh, untreated samples must also be dialyzed or desalted before assaying by the cytochrome c method. Cu,ZnSOD activity is equal to the activity in the untreated sample minus the activity in the DDC-treated portion of the sample. Another copper chelator, triethylenetetramine, did not inactivate Cu,ZnSOD and could not be used instead of DDC. For accurate measurement of both enzymes in samples where MnSOD contributes only a small fraction of the total SOD activity, the DDC method has the advantage that it provides a direct measure of the MnSOD activity without interference by Cu,ZnSOD.

Animals

Immunoturbidimetric assay for estimating free light chains of immunoglobulins in urine and serum.

An immunoturbidimetric assay for the assessment of free kappa and lambda light chains of immunoglobulins was developed using a commercial polyclonal antiserum with reactivity towards epitopes on the light chains, which are not expressed when they are bound to heavy chains. The assay, on a centrifugal analyser, is simple and rapid. The limit of detection is 5 mg/l of free light chain, with an assay range of 5-120 mg/l, intrabatch precisions from 1.5-6.4%, and interbatch precisions from 6.5-8.9%. The assay was only slightly less sensitive than colloidal gold staining of cellulose acetate electrophoreses for the detection of Bence-Jones protein in urine. For the serial monitoring of response to chemotherapy in patients with myeloma, the assay correlated well with serum paraprotein estimates obtained by densitometric scanning of Ponceau stained cellulose acetate electrophoreses, but not with serum beta-2 microglobulin measurements, even after correction for the effects of creatinine. These assays may prove to be of use for the monitoring of tumour response in the treatment of Bence-Jones myeloma.

Antibodies, Neoplasm

Perinatal rat lung catalase gene expression: influence of corticosteroid and hyperoxia.

Dexamethasone accelerates the late gestational rise in rat lung catalase activity; neonatal hyperoxia elevates rat lung catalase activity. We studied the regulation of catalase gene expression in these instances. Catalase mRNA/mg DNA increased to gestation day 22 and then fell to the concentration in adult lungs. The rate of transcription of catalase mRNA was higher on gestation day 22 than gestation day 19, whereas the half-life of catalase mRNA (approximately 7 h) was the same on both days. Dexamethasone given 48 and 24 h before expected birth (gestation 22 days) increased catalase mRNA concentration at days 20 and 22 without a change in catalase mRNA stability. Early postnatal hyperoxia (greater than 95% O2, 72 h) elevated catalase mRNA/mg DNA and doubled its half-life without changing its rate of transcription. We conclude the normal late gestational elevation of catalase activity and the increase of activity during prenatal dexamethasone treatment are regulated at the level of gene transcription. By contrast, the elevation of catalase activity during neonatal hyperoxia is mediated posttranscriptionally by increased catalase mRNA stability.

Aging

Toxoplasmic lymphadenitis--a clinicopathological study.

Forty-three cases of toxoplasmic lymphadenitis were studied. They constituted 0.5% of all lymph node biopsies and 4.2% of reactive lymphadenitis. The histological findings supporting a diagnosis of toxoplasmosis were correlated with serological studies. The condition primarily affects young men, causing cervical lymph node enlargement and varying degrees of fatigue, malaise, cough and fever. It is usually self-limited. This study emphasizes the need for clinicians to consider toxoplasmosis in the differential diagnosis of lymphadenopathies.

Adolescent

Histiocytic necrotizing lymphadenitis. A clinicopathological study.

Seven cases of Histiocytic necrotizing Lymphadenitis (HNL) were studied. They constituted 0.56% of all lymph nodes biopsies. The condition primarily affects young women causing cervical lymph node enlargement and leukopenia. The basic lesion is characterized by proliferation of lymphocytes and histiocytes with nuclear debris in the para cortex and cortex. This study examined various bacterial, viral and immunological factors which could possibly be responsible for this condition. However, it failed to find positive association with any of them. The existence of this disease in Pakistan is documented.

Adolescent

Cytochrome P450 reductase, antioxidant enzymes and cellular resistance to doxorubicin.

Our data suggest that DOX resistance in P388/R-84 cells may result, at least in part, from reduced free radical formation by both suppression of flavin reductase(s) and overexpression of certain antioxidant enzymes such as GSH peroxidase and catalase. In addition, our results, in conjunction with other studies, indicate that flavin reductase(s) and antioxidant enzymes are differentially altered in cancer cells with acquired or de novo resistance to DOX. Further studies are needed, however, to elucidate the mechanism(s) by which the gene expression of these enzymes is regulated in drug-sensitive and -resistant cells.

Animals

A clinical audit of thallium-technetium subtraction parathyroid scans.

Eighty six consecutive thallium-technetium subtraction parathyroid scans performed over a three year period for hypercalcaemia have been evaluated. Twelve had chronic renal failure, 11 had hypercalcaemia due to non-hyperparathyroid causes and in 10 the imaging study was technically inadequate. The remaining 53 technically adequate studies performed for hypercalcaemia clinically thought to be possibly due to hyperparathyroidism have been analysed. Of 20 (38%) positive scans, 13 came to surgery (10 correctly localized parathyroid adenomas, 2 with multiple gland hyperplasia, and 1 papillary carcinoma of the thyroid). Of 33 (62%) negative scans, 9 had surgical exploration on the basis of strong clinical grounds and all had parathyroid adenomas. Multiple biochemical parameters have been assessed in relation to a positive outcome on scan. The adjusted calcium-phosphate product and the ratio of the adjusted calcium-phosphate product to creatinine (Ca x P/Cr) were both significantly lower in the scan positive group (P less than 0.01). The scan positive group had a significantly higher mean level of PTH (P less than 0.001) and lower mean level of phosphate (P less than 0.001). The present experience shows that parathyroid imaging is useful in localizing parathyroid adenomas in 50% of cases (10 out of 19). This figure is at the lower end of the range of previously published results. It is less effective in demonstrating multiple gland hyperplasia. The decision as to whether to undertake surgical exploration when the scan is negative has been based successfully on clinical judgement. We feel that an analysis of this nature is important, as it gives insights into the practical relevance of parathyroid imaging in the context of routine clinical work.

Adenoma

Antidiabetic evaluation of Mucuna pruriens, Linn seeds.

Effects of powdered Mucuna pruriens seeds on blood glucose levels were investigated in normal and alloxan-diabetic rabbits. In normal group 0.5, 1 and 2 g/kg of M. pruriens pulv significantly decreased the blood glucose levels while in alloxan-diabetic rabbits only 1 and 2 g/kg body weight caused a significant fall. The reference drug, acetohexamide in 500 mg/kg dose significantly reduced the blood glucose levels but in normal rabbits only. High levels of trace elements like manganese, zinc, and others were found in these seeds. Therefore, it is conceivable that M. pruriens seeds contain hypoglycaemic principles, may be both organic and mineral, which seem to act indirectly by stimulating the release of insulin and/or by a direct insulin-like action.

Alloxan

Endotoxin increases lung Cu,Zn superoxide dismutase mRNA: O2 raises enzyme synthesis.

Administration of endotoxin to adult rats increases lung Cu,Zn superoxide activity after 72 h of exposure to greater than 95% O2. The increased activity is brought about mainly by a faster rate of Cu,Zn superoxide dismutase synthesis; rats treated with endotoxin but not exposed to hyperoxia do not exhibit these findings (Hass, Frank, and Massaro, J. Biol. Chem. 257: 9379-9383, 1982). We now report that 48 h after treatment of adult rats with endotoxin there was a decreased rate of Cu,Zn superoxide dismutase synthesis by lung slices from air- and O2- exposed rats, although, in both groups, the lung concentration of Cu,Zn superoxide dismutase mRNA was increased approximately 45%. Exposure of endotoxin-treated rats to greater than 95% O2 or air for an additional 24 h (72 h all told) resulted in continued elevation of Cu,Zn superoxide dismutase mRNA only in lungs of O2- exposed rats. In vitro exposure of lung slices from air-breathing saline- or endotoxin-treated rats to 95% O2 for 6 h led to an increased rate of Cu,Zn superoxide dismutase synthesis only in slices from endotoxin-treated rats. We conclude that endotoxin treatment leads to an increased concentration of Cu,Zn superoxide dismutase mRNA in rat lungs, but a sustained elevation of the mRNA, and its translation into an increased rate of Cu,Zn superoxide dismutase synthesis requires exposure of the lung to hyperoxia.

Animals

New "rest period" protocol for inducing tolerance to high O2 exposure in adult rats.

We report a new protocol for inducing marked tolerance to prolonged exposure to hyperoxia in adult rats that entails the use of a single "rest period" between exposures to a usually lethal concentration of O2. Exposure of adult rats to greater than 95% O2 for 48 h followed by a rest in air, or a rest even in 50-75% O2, consistently resulted in 100% survival with evidence of only slight pulmonary edema during continuation of exposure to greater than 95% O2 for 3-7 more days (7-day survival for rats rested in room air for 24 h = 23/23; for rats rested in 50-75% O2 for 24 h = 27/27; for continuously O2-exposed control rats = 0/11). Induction of tolerance to hyperoxia was associated with significant increases in the lungs' antioxidant enzyme activities during the reexposure to greater than 95% O2 following the rest period. The molecular means by which the events in this protocol lead to increased lung antioxidant enzyme activity is only partially known, but because of the marked tolerance produced, the elucidation of the mechanisms must be important to our understanding of tolerance to hyperoxia.

Animals

Rat lung Cu,Zn superoxide dismutase. Isolation and sequence of a full-length cDNA and studies of enzyme induction.

The synthesis of Cu,Zn SOD by rat lung increases spontaneously in the fetus in late gestation and during exposure of neonatal and adult rats to greater than 95% O2. To explore the regulation of these increases, we measured rat lung Cu,Zn SOD synthesis and activity. We also cloned and sequenced a rat lung Cu,Zn SOD cDNA that was used to measure Cu,Zn SOD mRNA concentration. We found that (a) under normal gestational and postgestational conditions the synthesis of this enzyme was regulated pretranslationally; (b) the increased synthesis that occurs under hyperoxia (greater than 95% O2), was pretranslationally mediated in otherwise unmanipulated neonatal rats but translationally controlled in hyperoxic adult rats; and (c) in lungs of rats made tolerant to greater than 95% O2 by allowing 24 h rest in air after an initial 48 h in greater than 95% O2, the increased Cu,Zn SOD synthesis that occurred during the second period of hyperoxia was regulated pretranslationally. We conclude Cu,Zn SOD gene expression in the lung is developmentally regulated under normal conditions and in response to an oxidant challenge. Tolerance, whether endogenous or induced, appears to require the accumulation of increased amounts of Cu,Zn SOD mRNA.

Aging

Visceral leishmaniasis: a seroepidemiological study of 289 children from endemic foci in Azad Jammu and Kashmir by indirect fluorescent antibody technique.

Between January '85 and August '87, 22 cases of VL were seen at National Institute of Health, Islamabad. Three (14.6%) came from the previously known endemic region of Gilgit, 15 (68.1%) from different localities in Azad Jammu and Kashmir (AJ&K), and 4 (17.3%) from neighbouring foci in NWFP and Punjab. Mean age of the patients was 4.2 years, (Range, 10 months to 57 years) median 2.5 years and mode 2 years. High levels of Leishmania antibodies were detected by Indirect Immunofluorescent Antibody Technique (IFAT) in all cases. Leishmania were isolated from bone marrow aspirates of 2 patients and isoenzyme characterization performed in one of these, the organism was typed as Leishmania infantum sensu stricto. Sera from 289 children residing in 5 endemic localities in AJ&K was tested for Leishmania specific antibodies by IFAT and low levels of these antibodies were detected in 15.4% of the cases.

Child