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Biomedical subjects

A Mahmood

Publications and source records attributed to A Mahmood.

At least 109 records · Page 6Linked to original sources

Expression of brush border enzymes in ethanol fed rat intestine.

The effect of feeding ethanol daily for 40 days was studied on various brush border enzymes in rat intestine. Brush border alkaline phosphatase (AP), lactase, gamma-glutamyltranspeptidase (gamma-GTP), p-nitrophenyl (PNP)-beta-D-galactosidase (P < 0.01) and sucrase (P < 0.001) were significantly enhanced while leucine aminopeptidase and PNP-beta-D-glucosidase activities were unaltered in ethanol fed rats compared to the controls. Kinetic studies revealed that an increase in Vmax together with a decrease in affinity in case of gamma-GTP and an increase in Vmax for AP and sucrase were responsible for the observed stimulation of enzyme activities in ethanol administered rats. Significant changes in enzyme activities were observed in different populations of enterocytes along the crypt-villus unit in the ethanol fed animals. These observations suggest that ethanol feeding modifies the brush border enzymes in rat intestine but the underlying mechanisms seem to be distinct in differentiating enterocytes.

Alkaline Phosphatase↗

The secretion of intestinal alkaline phosphatase (IAP) from the enterocyte.

Rat intestinal alkaline phosphatase exists in two separate forms, differing markedly in the carboxyterminal coding region, as well as in the 3' untranslated regions. It is secreted bound to a phospholipid-rich particle (surfactant-like particle) which appears to have unique properties, but whose role is still uncertain. Evidence is presented to suggest that intestinal alkaline phosphatase secretion is mediated by this particle. The challenge for the future is to study the biology of the surfactant-like particle, to ascertain its role in gut physiology, and to determine how the dual alkaline phosphatases are involved in this specialized secretory apparatus.

Alkaline Phosphatase↗

Inhibition of rabbit intestinal brush border sucrase by indolin 2,3-dione (isatin) at pH 5.0.

Isatin (10 mM) inhibited the activity of rabbit brush border sucrase by 60% at pH 5.0 but it had no effect on enzyme activity around neutral pH. Isatin inhibition of sucrase was unaffected by Na+ ions but K+ and Cs+ ions reduced enzyme inhibition, partially. Kinetic analysis revealed that sucrase inhibition by isatin at acidic pH was non-competitive with Ki of the order 6.5-7.8 mM. Isatin together with 4 mM harmaline or iodoacetate (3 mM) or dithionitrobenzene (2 mM) yielded 80-85% inhibition of the enzyme. These observations suggest that inhibitory sites for isatin, harmaline and -SH group reacting agents are distinct in rabbit brush border sucrase.

Animals↗

Giant cell tumor of the skull base.

Giant cell tumor of the skull is a rare clinical entity. This report presents the case of a 32-year-old female with Turner's syndrome and a giant cell tumor of the left middle cranial fossa floor. Although there have been sporadic reports of patients with extragonadal tumors, to our knowledge this is the first reported case of giant cell tumor in a patient with Turner's syndrome. Definitive treatment is surgical extirpation; however, recommendations for cases of subtotal excision remain controversial. Management of this patient with giant cell tumor of the skull is described, and current treatment recommendations are discussed.

Adult↗

Characterization of proteins in rat and human intestinal surfactant-like particles.

Phospholipid-rich particles isolated from the apical surface of rat enterocytes have surfactant-like properties and are enriched for intestinal alkaline phosphatase. Purified intact rat particles were used to produce antibodies in rabbits. Antiserum against the rat particle identified major proteins of 48, 68, 98, and 118 kDa on Western blots of isolated rat surfactant-like particle and did not detect any protein in rat intestinal basolateral membranes, rat brush border membranes, or human particles, but did detect a single 180-kDa protein in a preparation of rat milk fat globules, and two proteins (66 and 103 kDa) in rat pulmonary surfactant. The proteins detected on Western blot corresponded with the major proteins identified by Coomassie blue staining. Similar particles were isolated from the apical surface of human intestine and had an enzyme composition, buoyant density, and lipid content similar to those of the rat particles. Antiserum raised against the human jejunal particle detected proteins in the human particle by Western blot that were similar in size with the rat particle proteins (33, 52, 75, 82, and 118 kDa), but did not cross-react with human brush border or rat particle proteins. These studies demonstrate that the surfactant-like particles are present in human as well as rat intestinal tissue, demonstrate similar enzyme and protein content, and confirm their unique identity, distinct from apical brush border or basolateral membranes.

Animals↗

Atypical and malignant meningiomas: a clinicopathological review.

There has been continuing debate on the subject of malignant meningiomas, but few studies of large series have been reported. We present our experiences with 25 atypical and malignant meningiomas operated on at Henry Ford Hospital between 1976 and 1990. A total of 319 primary intracranial meningiomas were operated on during this period; of these, 294 (92%) were benign, 20 (6.26%) atypical, and 5 (1.7%) malignant. We used a modified histological grading system, based primarily on World Health Organization criteria of malignancy (hypercellularity, loss of architecture, nuclear pleomorphism, mitotic index, tumor necrosis, and brain invasion), to define atypical and malignant meningiomas. Each of these criteria was given a score from 0 to 3, and then partial scores were added to obtain cumulative scores. These total scores were then used to determine what is benign, atypical, and malignant. The peak incidence of atypical and malignant meningiomas was in the seventh and sixth decades, respectively. The predominance of female patients with benign meningiomas was not observed in the nonbenign group. The male:female ratio for atypical and malignant meningiomas was 1:0.9 versus 1:2.3 for benign meningiomas (P = 0.024). The most common presenting symptom and physical sign in our patients was paresis. In reviewing their radiographic features, all patients showed moderate or marked edema on computed tomography. Calcification was exhibited by one patient only and "mushrooming" was seen in three cases. Of the 25 patients, 11 (44%) died during follow-up: 2 in the perioperative period, 8 within the first 5 years, and 1 died 11 years after the diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Effect of feeding high fat, high fiber diet on brush border enzymes in mice intestine.

The effect of dietary fat content on brush border enzymes has been studied in mice intestine. The results obtained from 26 per cent fat (high fat; HF)-fed mice were compared with those fed 10 per cent fat (pair-fed; PF and ad libitum-fed). Brush border alkaline phosphatase (AP), leucineaminopeptidase (LAP) and gamma-glutamyltranspeptidase (gamma-GTP) activities were significantly enhanced while sucrase activity was reduced (P < 0.001) in HF group compared to the controls. Activities of lactase, p-nitrophenyl (PNP)-beta-D-glucosidase and PNP-beta-D-galactosidase were unaltered under these conditions. Kinetic studies with AP, sucrase and LAP revealed that changes in enzyme levels in response to HF diet were due to change in Vmax. Significant changes in enzyme activities as a consequence of HF intake were observed in enterocytes all along the crypt-villus unit as compared to the control group. These results indicated that feeding a fat-rich diet produced selective changes in brush border enzyme activities in mice intestine.

Animals↗

Effect of pH and sodium ions on intestinal uptake of lysine in rats.

Intestinal uptake of lysine in rats progressively decreased with an increase in pH from 5.2 to 8.5, both in the presence and absence of Na+ ions. At pH 5.2 lysine uptake was 30-35% more than that at neutral pH. Na+ activated lysine uptake by 40-50% at pH 5.2 and it was increased to 110-120% at neutral pH. The observed increase in lysine uptake in response to Na+ and H+ gradients was due to enhanced maximal velocity (Vmax), with little change in affinity constant (Kt). Arrhenius analysis revealed a biphasic curve for lysine uptake with transition temperature (Tc) around 20 degrees C (24 degrees C at pH 5.2 in presence of Na+). The energy of activation (Ea) below (16.1-23.4 Kcal/mole) and above (6.7-8.6 Kcal/mole) the Tc was similar at pH 5.2 and 7.0 both in the presence and absence of Na+ ions. The sensitivity of lysine uptake to various inhibitors was also dependent upon pH and Na+ ions.

Animals↗

Effect of high-fat diet on mice intestinal brush border membrane composition.

Effect of feeding high-fat (26% fat) diet to mice for 21 days on intestinal brush border membrane composition was evaluated by comparing with controls fed 10% fat diet. 125I-labelled lectin binding and chemical analysis of fucose, sialic acid, hexoses and hexosamines revealed essentially similar results in control and test groups. Membrane phospholipids, expressed on dry membrane basis, were significantly reduced while total cholesterol was enhanced in experimental group compared to controls. Triglyceride content was not altered under these conditions. [14C]-acetate incorporation studies showed that decrease in phospholipid content was due to reduced synthesis of phospholipid constituents, in particular, phosphatidylcholine and phosphatidylethanolamine, as a result of feeding high fat diet. The results suggest that high amount of fat in the diet of adult mice does not alter sugar content in brush border membrane but affects membrane lipid composition.

Animals↗

Microsurgical anatomy of the lower basilar artery.

This study was designed to study the microvascular anatomy of the basilar artery between the superior cerebellar artery and the vertebrobasilar junction (i.e. the lower basilar artery). Twenty unfixed brains were injected with silicone rubber solution and studied with a Zeiss OPMI microscope. The length of this segment of the basilar artery was 28.1 + 1.35 mm and its course was straight in 9 (45%) brains, curved in 7 (35%) and tortuous in 4 (20%). The total number of perforators found in 20 brains was 340 with an average of 17 per brain. Of these, 118 (34.7%) were median and 222 (65.2%) were lateral. Median branches had a mean length of 5.8 + 1.25 mm, whereas left and right lateral branches had a mean length of 16 + 1.25 mm and 16 + 1.58 mm respectively.

Autopsy↗

An open clinical pilot study of the efficacy and safety of oral terbinafine in dry non-inflammatory tinea capitis.

Ten patients with dry non-inflammatory tinea capitis were evaluated in a pilot study which ran from September 1989 to February 1990. Each patient was given oral terbinafine for 6 weeks; each was followed up 2 weeks later. Eight (80%) were completely cured, one (10%) was mycologically cured and showed minimal signs and symptoms, and another (10%) showed improvement (negative mycology, but persistent clinical signs and symptoms). No topical or systemic side-effects were noted. Terbinafine appears to be an effective and safe antifungal agent in the treatment of non-inflammatory tinea capitis.

Adolescent↗

Caco-2 cell transfection by rat intestinal alkaline phosphatase cDNA increases surfactant-like particles.

The rat enterocyte produces a particle with surfactant-like properties (including a whorled appearance, enrichment for dipalmitoyl phosphatidylcholine, and ability to lower surface tension) that also is enriched for intestinal alkaline phosphatase. Human Caco-2 cells grown on polycarbonate filters were utilized to study the secretion of these particles and exhibited whorls and strands of unilamellar membranes, particularly concentrated at the apical pole or near junctional complexes. Concentrated culture medium from these cells separated on continuous NaBr gradients revealed a fraction at density = 1.07 g/l enriched for phosphatidylcholine and intestinal alkaline phosphatase. This fraction contained membranous sheets containing alkaline phosphatase, detected by immunolocalization. Phosphatidylcholine comprised 54% of phospholipid in this fraction, compared with 20% in brush borders. When Caco-2 cells were transfected with cDNA encoding rat intestinal alkaline phosphatase, cellular phosphatase activity increased twofold, but activity in the medium increased 14-fold to > 200 (average 32)-fold. Ultrastructurally, compared with mock-transfected cells or cells transfected with human placental alkaline phosphatase, transfection with rat intestinal alkaline phosphatase cDNA led to intracellular and extracellular accumulation of surfactant-like particles. We conclude that surfactant-like particles are produced by Caco-2 cells, and their production can be enhanced by transfection with a cDNA encoding a protein known to be associated with such particles.

Alkaline Phosphatase↗

Intestinal epithelial cell surface glycosylation in mice. 1. Effect of low-protein diet.

Mice fed on an 8% protein (low-protein; LP) diet for 21 days exhibited a significant (p less than 0.001) decrease in their body weights compared with the pair-fed controls (18% protein). Brush border enzyme analysis revealed a 56% increase in sucrase activity and a significant decrease in alkaline phosphatase (p less than 0.05), beta-D-glucosidase (p less than 0.001) and beta-D-galactosidase (p less than 0.05) activities in protein-deficient mice. Lactase activity was unaltered in these conditions. Hexose and hexosamine contents of the brush border membranes (BBM) decreased considerably as a result of the LP diet. Protein deprivation significantly enhanced (p less than 0.01) brush border sialic acid and reduced (p less than 0.05) fucose content compared to the controls. The binding of 125I-labelled wheat germ agglutinin and Ulex europaeus agglutinin I to BBM was in agreement with the data on sialic acid and fucose levels of the membranes. The binding of peanut agglutinin to BBM was 38% higher in LP-diet-fed animals. The incorporation of [14C]mannose and [14C]glucosamine into BBM was markedly reduced (25%), while that of [3H]fucose was apparently unaffected. These results suggest that the feeding of an LP diet to mice results in marked alterations in the intestinal epithelial cell surface glycosylation.

Animals↗

Tenosynovial giant-cell tumor of the cervical spine. Case report.

A case of tenosynovial giant-cell tumor affecting the cervical spine is reported. The lesion is seen primarily in the fingers, knee, or ankle, and there are no previous reports of it occurring in the spine. The histological and radiological features of this tumor are discussed along with a brief description of the disease entity.

Adult↗

Effect of divalent metal ions on soluble and membrane-bound alkaline phosphatase activity in suckling rat intestine.

EDTA treatment of intestinal brush border membranes (BBM) and epithelial cell supernatant completely inhibited alkaline phosphatase (AP) activity in suckling rat intestine. AP activity was fully regained upon dialysis of the preparations against Zn2+ and to a lesser extent against Co2+, Ca2+ and Mn2+ ions. Other metal ions (Cd2+ and Mg2+) tested were essentially ineffective in restoring the enzyme activity. Considerable differences were observed in kinetic characteristics of the membrane-bound and soluble AP activities in response to various metal ions. There were apparent differences in Km, Vmax, energy of activation (Ea) and thermal stability of the soluble and membrane-bound AP activities, after metal ion substitutions. Nearly 35% AP activity was solubilized on sodium dodecyl sulphate treatment of brush borders (membrane protein: detergent ratio 1:3; w/w). Dialysis of detergent solubilized BBM against different metal ions reconstituted AP activity in the particulate fraction: the order of effectiveness was Zn greater than Ca greater than Mn greater than Co. The kinetic properties of the reconstituted AP were essentially similar to the non-integrated enzyme activity in response to various divalent metal ions examined. But there were apparent differences in Km, Vmax, Ea and thermal stability of the reconstituted AP activity compared to native brush border enzyme. The results suggest the unique requirement of Zn ions for stability and catalytic activity of the soluble and membrane-bound AP activity in suckling rat intestine.

Alkaline Phosphatase↗

Structure of a neutral N-alkylated diaminedithiol (dadt) 99TcV complex: syn[99TcO(NEt-tmdadt)].

syn-(4-Ethyl-2,9-dimethyl-4,7-diaza-2,9-decanedithiolato)oxo (99Tc) technetium(V), syn-[99TcO(NEt-tmdadt)], [Tc(O)(C12H25N2S2)], Mr = 375, monoclinic, P2(1)/n, a = 9.638(2), b = 14.371(5), c = 11.893(3) A, beta = 100.79(2) degrees, V = 1618.15(75) A3, Z = 4, Dx = 1.54 g cm-3, lambda(Mo K alpha) = 0.71069 A, mu = 11.0 cm-1, F(000) = 776, T = 293 K, R = 0.028, wR = 0.042 for 2788 unique observed reflections with I greater than sigma(I). This study is the first which conclusively establishes the structure of the major complex derived from the reaction of an N-substituted diaminedithiol ligand with reduced pertechnetate. An intramolecular repulsion exists between the ethyl substituent and the oxo-metal core, resulting in a larger-than-expected angle for N(2)-Tc-O, 104.7(1) degrees.

Molecular Structure↗

Rat intestinal alkaline phosphatase secretion into lumen and serum is coordinately regulated.

We have reported the presence of intestinal alkaline phosphatase on particles with surfactant-like properties within enterocytes, on the luminal surface (light mucosal scrapings) and in the lumen of adult fat-fed rat intestines ((1989) J. Clin. Invest. 84, 1355). To test the physiological role of these particles, we compared the effect on particle secretion of a known inducer of luminal and serum alkaline phosphatase secretion (fat), with the effect of pharmacological stimulators (cholecystokinin and bethanecol). Fat induced a 2-3-fold increase in membrane-free phosphatase activity in serum, and in particle-bound alkaline phosphatase activity in proximal luminal washings and light mucosal scrapings, reaching a peak in both compartments 7 h after a corn oil feed. Bethanecol given subcutaneously induced a quantitatively similar increase in serum alkaline phosphatase activity and in particle-bound phosphatase activity in proximal light mucosal scrapings, reaching a peak 7.5 min after injection. Cholecystokinin also had a 2-3-fold stimulatory effect, 30 min after injection, on particle-bound phosphatase activity in proximal intestinal light mucosal scrapings and distal intestinal luminal washings. The increase in alkaline phosphatase activity in serum samples reached a peak 60 min after cholecystokinin injection. Thus, three independent stimuli increase both luminal and serum appearance of intestinal alkaline phosphatase. These data support the earlier findings that intestinal alkaline phosphatase secretion into the lumen is mediated by a secreted particle, further show that secretion into serum and lumen is coordinately regulated, and are consistent with the hypothesis that the rise in serum alkaline phosphatase activity could be related to extracellular release of the enzyme from the particles.

Alkaline Phosphatase↗