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Biomedical subjects

Z Iqbal

Publications and source records attributed to Z Iqbal.

At least 55 records · Page 3Linked to original sources
PubMed1994

Comparison of PCR with other tests for early diagnosis of canine ehrlichiosis.

The purpose of the study was to compare the sensitivity of PCR with those of cell culture reisolation of Ehrlichia canis, the indirect fluorescent antibody test (IFA), and Western immunoblotting (WI) in the early diagnosis of canine ehrlichiosis. Five German shepherd dogs were intravenously inoculated with 10(7) E. canis-infected DH82 cells. Blood was collected on alternate days during a 2-week postinoculation period. Mononuclear cell fractions were harvested and used for E. canis reisolation and DNA extraction for PCR. The plasma was used for assaying antibodies against E. canis. By PCR, the 16S rRNA gene of E. canis was detected in the mononuclear cell specimens collected as early as day 4 to 10 postexposure (PE). E. canis was reisolated from the blood starting on day 2 PE from all five dogs. The indirect fluorescent antibody test and Western immunoblotting could detect E. canis antibodies as early as 2 to 8 days PE. Cell culture reisolation proved to be the most sensitive and definitive for early diagnosis of ehrlichiosis, but it is not very convenient, since it takes a long time (14 to 34 days) to show up positive. The sensitivity of PCR is comparable to or slightly less than that of other established methods; however, the convenience, quickness, and direct nature of detecting E. canis DNA is expected to make PCR more useful for clinical diagnosis.

Animals↗
PubMed1994

Glucocorticoid action on depolarization-dependent calcium influx in brain synaptosomes.

Synaptic plasma membranes from the brain are known to have specific binding sites for several steroid hormones, but the mechanism of membrane transduction of steroid signals is not understood. In this study, corticosterone was found to stimulate 45Ca2+ uptake in brain synaptosomes upon depolarization of the synaptosomes by high K+ (70 mM). The stimulation of the depolarization-dependent 45Ca2+ uptake by corticosterone is concentration dependent, with the maximal effect occurring at steroid concentration of 5-10 x 10(-7) M (70-80% above control). The EC50 is estimated as 1.3 x 10(-7) M, which is almost identical to the Kd of the specific binding of the steroid to synaptic membranes (1.2 x 10(-7) M) reported previously. The stimulation of 45Ca2+ uptake in brain synaptosomes is specific to corticosterone and other glucocorticoids (cortisol, dexamethasone and triamcinolone); gonadal steroids (17 beta-estradiol, progesterone and testosterone) are ineffective. [3H]Nitrendipine binding was used to examine the effect of corticosterone on voltage-dependent Ca2+ channels. No effect on [3H]nitrendipine binding was found when disrupted synaptic membranes were preincubated with the steroid. However, a significant increase of membrane binding of [3H]nitrendipine was found when intact synaptosomes were first preincubated with the steroid at 37 degrees C and then disrupted. Steroid preincubation of synaptosomes at 0 degrees C was ineffective. Since preincubation at 37 degrees C is required, it appears that metabolic processes modulating Ca2+ channel activity are involved in the steroid action.

Animals↗
PubMed1994

Ethanol modulates [125I]calmodulin binding to synaptic plasma membranes from rat brain.

The effects of ethanol in vitro on Ca(++)-dependent binding of [125I] calmodulin to brain synaptic plasma membranes (SPM) from control and chronically ethanol-treated rats were studied. In SPM from control animals, ethanol at 50 to 200 mM inhibited [125I] calmodulin binding; the inhibition was correlated with a decreased membrane affinity for [125I]calmodulin as shown by Scatchard analysis, and an increased dissociation of [125I]calmodulin-membrane complexes as shown by kinetic analysis. Arrhenius analysis indicates that [125I]calmodulin binding was influenced by lipid transition of the membrane, and that ethanol in vitro resulted in a shift of the transition temperature toward a lower value. From animals receiving chronic ethanol treatment (3 weeks), the SPM were found to be resistant to the inhibitory effect of ethanol on binding. The resistance to ethanol inhibition was correlated with a higher membrane affinity for [125I]calmodulin and a higher transition temperature, as compared with control SPM. Because a variety of membrane-bound processes are regulated by calmodulin or calmodulin-dependent processes, the inhibitory effect of ethanol on membrane binding of calmodulin could lead to a cascade of consequences in synaptic function. Moreover, the resistance of the membranes to ethanol inhibition after chronic ethanol treatment implies that membrane binding of calmodulin is part of the mechanism underlying alcohol tolerance and dependence.

Animals↗
PubMed1993

Amyotrophic lateral sclerosis and structural defects in Cu,Zn superoxide dismutase.

Single-site mutants in the Cu,Zn superoxide dismutase (SOD) gene (SOD1) occur in patients with the fatal neurodegenerative disorder familial amyotrophic lateral sclerosis (FALS). Complete screening of the SOD1 coding region revealed that the mutation Ala4 to Val in exon 1 was the most frequent one; mutations were identified in exons 2, 4, and 5 but not in the active site region formed by exon 3. The 2.4 A crystal structure of human SOD, along with two other SOD structures, established that all 12 observed FALS mutant sites alter conserved interactions critical to the beta-barrel fold and dimer contact, rather than catalysis. Red cells from heterozygotes had less than 50 percent normal SOD activity, consistent with a structurally defective SOD dimer. Thus, defective SOD is linked to motor neuron death and carries implications for understanding and possible treatment of FALS.

Amino Acid Sequence↗
PubMed1993

[125I]calmodulin binding to synaptic plasma membrane from rat brain: kinetic and Arrhenius analysis.

Binding of [125I]calmodulin was characterized in highly purified synaptic plasma membrane (SPM) prepared from rat brain. By Scatchard analysis, the Ca(2+)-dependent membrane binding of [125I]calmodulin was found to have a Bmax of 284 pmol/mg protein and an apparent affinity with a Kd of 131 nM. Kinetic analysis indicates that at 37 degrees C, the dissociation of [125I]calmodulin-membrane complexes follows first-order reaction and consists of two components: a dissociation constant (k) of 3.7 x 10(-1) min-1 and a half-time (t1/2) of 1.8 min for the fast component, and a k of 4.8 x 10(-2) min-1 and a t1/2 of 14.5 min for the slow component. At 0 degrees C, substantial dissociation still occurred, with a k of 4.5 x 10(-2) min-1 and a t1/2 of 15.3 min for the fast component, and a k of 5.5 x 10(-3) min-1 and a t1/2 of 125.5 min for the slow component. These data on binding affinity and dissociation kinetics are consistent with the notion that SPM can readily and rapidly associate and dissociate calmodulin. In Arrhenius analysis of temperature effects, [125I]calmodulin binding to SPM exhibits a biphasic function, with the transition temperature (Td) estimated to be 23.8 degrees C, suggesting that binding is influenced by lipid phase transition of the membrane. The binding of [125I]calmodulin to the synaptic membrane was found to be increased by corticosterone (10(-7)-10(-6) M), a steroid hormone, and decreased by ethanol (50-200 mM), a centrally acting drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

N-methyl-D-aspartate receptor excitotoxicity involves activation of polyamine synthesis: protection by alpha-difluoromethylornithine.

We investigated the role of polyamines and their regulatory enzyme ornithine decarboxylase in N-methyl-D-aspartate-induced excitotoxicity in embryonic chick retina. N-Methyl-D-aspartate (200 microM) produced an early increase in ornithine decarboxylase activity, putrescine concentration, and Ca2+ entry, leading to selective neuronal death by 30 min. This response was attenuated by the ornithine decarboxylase inhibitor alpha-difluoromethylornithine and the N-methyl-D-aspartate receptor antagonist 5-aminophosphonovaleric acid. Exogenous putrescine increased intracellular putrescine and spermine levels and reversed neuroprotection by alpha-difluoromethylornithine, but not by 5-aminophosphonovaleric acid. N-Methyl-D-aspartate-receptor stimulation of putrescine/polyamine synthesis mediates abnormal Ca2+ entry and acute excitotoxic neuronal death. Postreceptor inhibition of the ornithine decarboxylase/polyamine cascade by alpha-difluoromethylornithine may provide neuroprotection against N-methyl-D-aspartate-induced excitotoxicity.

Animals↗
PubMed1992

Changes in the expression of the tumor-associated antigen recognized by monoclonal antibody 44-3A6 in A549 cells due to calcium.

Although there is extensive data available on Ca2+ effects in normal tissues, comparatively little is known about its effects or regulation in tumor cells. The present studies were undertaken to investigate whether various extracellular calcium concentrations could modulate the expression of the tumor-associated antigen (TAA) recognized by monoclonal antibody (MAb) 44-3A6. It is highly expressed by the human lung adenocarcinoma cell line A549 and has been shown to be a 40-kD integral plasma membrane protein. Treatment of the A549 cell line with various concentrations of exogenous calcium showed a dose-dependent rise in the internal free calcium levels up to 2.4-2.9 mM (external calcium treatment). At higher concentrations, the internal calcium level showed a decline, indicating a higher calcium efflux. The calmodulin-dependent Ca(2+)-ATPase enzyme involved in calcium homeostasis was assayed under these same conditions. The enzyme activity increased with increasing external calcium concentrations showing a 5-fold increase in cells treated with 4.05 mM calcium. These data suggest that as the internal calcium approaches toxic levels, the Ca(2+)-regulated ATPase activity increases to reduce the calcium overload within the cell. Employing Western blot analysis and immunoperoxidase staining studies, this report shows that the antigen recognized by MAb 44-3A5 on A549 cells increased with an increase in calcium concentration. Evidence that this antigen is phosphorylated is presented using Western blot analysis of a radiolabeled antigen-enriched plasma membrane fraction. The previously reported subcellular localization, and now the phosphorylation and responsiveness to calcium by this TAA, gives it the properties predicted to be seen in a calcium 'pump-like' molecule. Thus, these studies support the hypothesis that this TAA may be important in intracellular calcium concentration control or that it is regulated via some calcium-mediated process.

Adenocarcinoma↗
PubMed1991

The hepatocellular thyroid status of uremic rats estimated from the abundances of thyroid hormone-dependent nucleoplasmic proteins.

Although the serum thyroxine (T4) and triiodothyronine (T3) concentrations of uremic rats are commensurate with moderate hypothyroidism, their thyroid status at the tissue level remains controversial. To help establish the hepatocellular thyroid status of uremic rats, a novel tissue marker (nuclear protein abundances) was evaluated in uremic rats (U), hypothyroid rats (H), and hypothyroid uremic rats (HU). Uremia was established by five-sixths nephrectomy. Moderate hypothyroidism was established by partial thyroidectomy or by provision of drinking water supplemented with propylthiouracil and T4. Normal rats (N) and pair-fed, sham-operated rats (1 to 3 weeks after surgery) served as controls. Animals were killed 1 to 5 weeks postoperatively. The following values were obtained 5 weeks after surgery, at which time the total and free serum T4 and T3 levels of the hypothyroid rats (H) were equivalent to those of the uremic rats (U). Total T4 (micrograms/dL +/- 1 SD): N, 5.4 +/- 1.7; H, 2.2 +/- 0.5; U, 1.9 +/- 1.5; HU, 0.5 +/- 0.0. Free T4 (ng/dL +/- 1 SD): N, 535 +/- 165; H, 126 +/- 37; U, 135 +/- 89; HU, 26 +/- 1. Total T3 (ng/dL +/- 1 SD): N, 63 +/- 20; H, 39 +/- 14; U, 38 +/- 18; HU, 13 +/- 4. Free T3 (ng/dL +/- 1 SD): N, 7.83 +/- 3.00; H, 3.87 +/- 1.05; U, 3.47 +/- 1.73; HU, 0.94 +/- 0.47. Hepatocellular thyroid status was estimated from the relative abundances of two nucleoplasmic proteins on polyacrylamide gel electrophoregrams.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Mental health services for deaf people: a need identified.

The unique problems of deaf people suffering from mental health conditions have long been recognised but have received inadequate attention in many parts of the country. In the absence of a specialist psychiatric service for deaf people in Wales a prevalence survey was conducted to estimate the numbers of deaf patients occupying long-stay mental health beds and to assess facilities available to them. A high prevalence of prelingual deafness was found in long-stay psychiatric inpatients, approximating to a relative risk ten times that in the general population. Throughout Wales there are approximately 100 patients with either prelingual or profound postlingual deafness resident in long-stay psychiatric and mental handicap beds. An inadequate provision of specialist support and equipment for all categories of deaf in-patients is demonstrated by the results of this study. Purchasers of mental health services must ensure that an acceptable quality of provision, including both access to a specialist psychiatric service and a supportive in-patient environment, is secured from providers.

Deafness↗
PubMed1990

Fine-needle aspiration biopsy of mucus-producing medullary carcinoma of thyroid: report of a case with cytologic, histologic, and ultrastructural correlations.

Cytologic features of aspiration smears from a mucus-producing medullary carcinoma of the thyroid are described. Two patterns of mucin production by the tumor cells were noted. In some cells, mucin was present as numerous small cytoplasmic vacuoles with ultrastructural morphology characteristic of mucin granules. Other cells had larger, more well-defined cytoplasmic mucin vacuoles; on ultrastructural examination, they were found to be intracytoplasmic lumina. Although mucin production has been demonstrated in several histologic studies of medullary carcinoma, it has not been previously recognized in fine-needle aspiration biopsies from this neoplasm.

Biopsy, Needle↗
PubMed1990

Geriatric diabetic nephropathy: an analysis of renal referral in patients age 60 or older.

We report a series of 33 consecutive hospitalized geriatric diabetic patients who were referred for evaluation of diabetic nephropathy, defined as proteinuria greater than or equal to 1 g/d (1,000 mg/24 h) or a serum creatinine concentration greater than or equal to 177 mumol/d (greater than or equal to 2 mg/dL). The study population was 60 years old or older (mean age, 68 +/- 6 years), was comprised mainly of women (24 of 33, 72.7%), and was predominantly black (25 of 33, 75.8%). All patients had type II diabetes. A family history of diabetes in parent or sibling was elicited in 24 (72.7%) patients. There were eight patients undergoing maintenance hemodialysis and 25 with less severe nephropathy (mean proteinuria, 2.7 g/d [2,700 mg/24 h]; mean creatinine clearance, 0.57 mL-s [34 mL/min]). Cardiac disorders were noted in the majority of patients: congestive failure in 20 (60.6%), myocardial infarction in eight (24.2%), and active angina in five (15.2%). Other comorbid diseases were present in both hemodialysis patients and the subset of nondialyzed azotemic-proteinuric patients, and consisted of peripheral neuropathy in 31 (93.9%), gastroparesis in 16 (48.5%), retinopathy in 28 (84.8%), and legal blindness in 11 (33%). We conclude that geriatric diabetic nephropathy in type II diabetes is similar in presentation and severity of comorbid extrarenal complications to the syndrome described in younger adults. This inference must be tempered by both the small size and the limitation imposed by the demographics of the study population, which is predominantly composed of black patients receiving treatment at inner city hospitals.

Aged↗
PubMed1990

Tissue-specific differences in the compartmentalization of rat nuclear triiodothyronine receptors.

In addition to the recognized rat liver nuclear T3 receptor extractable with hypertonic salt, recent studies have described nucleoplasmic receptors extractable with isotonic KCl and salt-resistant receptors localized to the nuclear matrix. A method was developed for the determination of intra-nuclear receptor distribution in small samples of nuclei dispersed within glass wool matrices. After in vitro labelling with 6 nmol/l [125I]T3, dispersed nuclei were sequentially extracted with 0.15 mol/l KCl (yielding nucleoplasmic receptors), 0.4 mol/l KCl. and 2 mol/l KCl (the latter two concentrations yielding hypertonic salt-extractable receptors). The salt-resistant receptors were retained within the glass wool columns. The intra-nuclear distribution of in vivo labelled receptors was very similar to that obtained by in vitro labelling. The equilibrium association constants for L-T3 binding among the receptor pools ranged from 0.6 X 10(9) to 1.0 X 10(9) l/mol. The distribution of total nuclear receptors within each nuclear compartment was (percentage of nucleoplasmic, hypertonic salt-extractable, and salt-resistant receptors): Cerebrum: 23.6, 52.2, 24.2; Liver: 25.2, 57.2, 17.5; Kidney: 45.9, 33.5, 20.6; Testis: 65.5, 14.7, 19.7; and Spleen: 66.7, 18.7, 14.6. The rank order of percentage of hypertonic salt-extractable receptors approximates the rank order of thyroid hormone-responsiveness by traditional criteria. The inverse is true for the percentage of nucleoplasmic receptors. The percentage of salt-resistant receptors was very similar in all of the tissues.

Animals↗
PubMed1990

Hepatic involvement with typhoid fever: a report of nine patients.

Salmonella typhi has been reported to cause hepatic involvement. We studied nine patients with positive blood cultures in order to identify characteristic features of typhoid hepatitis which may help in early diagnosis. Patients who had an illness resembling enteric fever but negative cultures for Salmonella typhi were excluded. No specific clinical features were found consistently and liver function tests were widely variable. Other biochemical abnormalities occurred due to vomiting and renal involvement. Liver biopsy showed focal hepatocellular necrosis and non specific inflammation. Although most responded to conventional antibiotics, it was generally a delayed response. It is recommended that patients with fever greater than 38.5 degrees C and liver abnormalities should undergo blood, urine, stool and/or bone marrow cultures. Liver biopsy may help to differentiate typhoid hepatitis from acute viral hepatitis.

Adolescent↗