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Biomedical subjects

A Shariff

Publications and source records attributed to A Shariff.

13 recordsLinked to original sources
PubMed2004

Changes in nitrergic innervation of defunctionalized rat colon after diversion colostomy.

After 45 days of complete diversion colostomy in male Wistar rats, morphometry of soma and nuclei of NADPH diaphorase positive cells of the myenteric plexus was evaluated. There was a significant (P < 0.0001) diminution in the area, perimeter and volume-weighted mean volume of soma and nuclei of nitrergic myenteric neurones in the defunctionalized colon. In addition, there was a significant reduction in the neuronal density of the myenteric neurones, and increased distance between the ganglia. In addition, there was myenteric glial atrophy. Atrophy of colonic myenteric neurones was accompanied by significant reduction (P < 0.001) in the volume fraction of the muscularis externa, the prime targets of these neurones. The disturbances in the microecology of the colon may jeopardize the finely orchestrated functioning of the components of the Enteric nervous system (ENS) leading to colonic dysfunction. Our observations, by extrapolation, may explain the bowel dysmotility in humans after restoration of colonic continuity after colostomy.

Animals↗
PubMed2004

Improving the selection of candidates for Royal Marine recruit training by the use of a combination of performance tests.

Candidates who wish to undertake Royal Marine recruit training, a physically strenuous course which now extends 32 weeks, must first of all successfully complete a Personal Qualities Assessment (PQA) and four psychomotor tests (Naval Recruiting Tests or RTs) before attending a three-day selection course at the Commando Training Centre, Lympstone, where their physical capabilities are tested to the full. The effectiveness of these procedures was untested until the Institute of Naval Medicine conducted a retrospective study during 1999-2000 from which the present study is taken. Data from 1232 recruits were examined to explore the relationship between the outcome of Commando training (pass or fail) with these various selection measures. Estimated aerobic power, time to complete the assault course and age were associated with outcome, as were PQA, RTs 1, 3, 4 and total RT score. A regression equation comprising aerobic fitness, assault course time, RT4 and age gave the best overall prediction of outcome (64%). It is suggested that this mathematical approach provides a scientifically valid and objective assessment tool for future selection strategies.

Adult↗
PubMed2002

Potential of MRI and 31P MRS in the evaluation of experimental testicular trauma.

OBJECTIVES: To prognosticate and assess the metabolic status of germ cells of the testis after unilateral blunt testicular trauma using both magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). MRI is a noninvasive technique suitable for evaluating testicular trauma, and MRS is useful in assessing the metabolic status of the testis. METHODS: The right testis of 35 male prepubertal Wistar rats, aged 30 days, was explored through an inguinal incision. The rats were randomized into control (group 1, sham surgery, n = 10) and study (n = 25) groups. The study group received unilateral blunt testicular trauma to the right testis. T(1)- and T(2)-weighted proton MRI of the ipsilateral testis were taken 6 hours after sham surgery or injury, and the rats were stratified on the basis of the absence or presence of intratesticular hemorrhage on MRI into groups 2 (n = 14) and 3 (n = 11), respectively. At 60 days of age, the contralateral testis of each rat was evaluated by 31P MRS and histologic examination. Quantification of phosphomonoesters, phosphodiesters, phosphocreatine, and adenosine triphosphate (gamma, alpha, and beta) was done. RESULTS: A statistically significant difference (P <0.05) in the phosphomonoester/adenosine triphosphate ratio, seminiferous tubular diameter, and Johnsen score of the contralateral testis was observed, indicating decreased testicular maturation of the contralateral testis in group 3 rats compared with groups 1 and 2. CONCLUSIONS: MRI after testicular trauma helped to stratify the extent of injury as determined by the presence or absence of intratesticular hemorrhage with prognostic value; 31P MRS and histologic examination revealed that testicular trauma significantly affects the maturation of the contralateral testis.

Age Factors↗
PubMed2001

A comparison of the intubating and standard laryngeal mask airways for airway management by inexperienced personnel.

Twenty-four inexperienced participants were timed inserting the intubating laryngeal mask airway and the laryngeal mask airway in 75 anaesthetised subjects. Adequacy of ventilation was assessed on a three-point scale. The pressure at which a leak first developed around the device's cuff was also measured. There was no significant difference in insertion time or the likelihood of achieving adequate ventilation between devices. However, the intubating laryngeal mask airway was better at providing adequate ventilation without audible leak (58/75 (77%) vs. 42/75 (56%); p = 0.009). The median (range [IQR]) pressure at which an audible leak developed was higher for the intubating laryngeal mask airway, 34.5 (14-40 [29-40]) cmH2O, than for the laryngeal mask airway, 27.5 (14-40 [22-33]) cmH2O (p < 0.001). The intubating laryngeal mask airway is worthy of further consideration as a tool for emergency airway management for inexperienced personnel.

Adolescent↗
PubMed2001

Symptom-directed selective endoscopy: long-term efficacy.

BACKGROUND: Synchronous primary neoplasms have been encountered in some patients with mucosal squamous cell carcinoma of the head and neck. Routine panendoscopy along with various radiological tests have been advocated to identify these potential tumors. In 1993, we originally described symptom-directed, selective endoscopy as an efficient and cost-effective means to evaluate patients to identify synchronous primary neoplasms. OBJECTIVE: To review the ultimate success rate of symptom-directed, selective endoscopy in that initial cohort of patients and the success of the program longitudinally in clinical practice over the intervening 6 years. PATIENTS AND METHODS: The status of the original 100 patients who participated in the selective endoscopy study were reviewed at least 6 months after the original procedure. A statistically significant random sample of 101 subsequent patients who had at least 6 months' follow-up or until their death were reviewed. RESULTS: No additional primary, mucosal head and neck, esophageal, or pulmonary cancers were identified in the surviving original cohort of patients suggesting that the selective endoscopy identified all synchronous tumors. Sixteen metachronous primary cancers were identified between 12 and 70 months after the initial evaluation. Eight synchronous primary cancers were identified in the new cohort using symptom-directed evaluation, direct laryngopharyngoscopy, and chest x-ray films. No additional tumors were detected within 6 months. CONCLUSION: Symptom-directed, selective endoscopy seems to be an effective alternative to routine panendoscopy in identifying synchronous primary cancers.

Cohort Studies↗
PubMed1997

Fine-needle aspiration of well differentiated small-cell duct carcinoma of the breast.

Historically, fine-needle aspiration of the female breast has been accepted as a useful modality in the diagnosis of ductal as well as other types of breast carcinoma. However, cases of well differentiated small-cell duct carcinoma can be problematic. The differential diagnoses include fibrocystic disease, papillary neoplasia, fibroadenoma, and lobular carcinoma. Retrospectively, 16 cases of well differentiated small-cell duct carcinoma have been identified in the case files of Truman Medical Center/University of Missouri-Kansas City. Patient's ages ranged from 29-81 yr, with the mean being 56.2 yr. The overall cytologic features consisted predominantly of a hypercellular specimen with cohesive and rarely discohesive cells with no demonstrable nuclear atypia. For well differentiated small-cell duct carcinoma, the mean nuclear diameter was greater than that of a red cell (6-8 microns). For the well differentiated small-cell duct carcinoma group, the mean nuclear diameter was 9.86 microns; for fibrocystic disease, 12.86 microns; for papillomas, 8.28 microns; for fibroadenomas, 9.48 microns; and for lobular carcinoma, 11.88 microns. From our data, it appears that specific attention to the clinical presentation, cytologic pattern, and nuclear diameters are useful discriminators for well differentiated small-cell duct carcinoma.

Adult↗
PubMed1993

The integral membrane protein, ponticulin, acts as a monomer in nucleating actin assembly.

Ponticulin, an F-actin binding transmembrane glycoprotein in Dictyostelium plasma membranes, was isolated by detergent extraction from cytoskeletons and purified to homogeneity. Ponticulin is an abundant membrane protein, averaging approximately 10(6) copies/cell, with an estimated surface density of approximately 300 per microns2. Ponticulin solubilized in octylglucoside exhibited hydrodynamic properties consistent with a ponticulin monomer in a spherical or slightly ellipsoidal detergent micelle with a total molecular mass of 56 +/- 6 kD. Purified ponticulin nucleated actin polymerization when reconstituted into Dictyostelium lipid vesicles, but not when a number of commercially available lipids and lipid mixtures were substituted for the endogenous lipid. The specific activity was consistent with that expected for a protein comprising 0.7 +/- 0.4%, by mass, of the plasma membrane protein. Ponticulin in octylglucoside micelles bound F-actin but did not nucleate actin assembly. Thus, ponticulin-mediated nucleation activity was sensitive to the lipid environment, a result frequently observed with transmembrane proteins. At most concentrations of Dictyostelium lipid, nucleation activity increased linearly with increasing amounts of ponticulin, suggesting that the nucleating species is a ponticulin monomer. Consistent with previous observations of lateral interactions between actin filaments and Dictyostelium plasma membranes, both ends of ponticulin-nucleated actin filaments appeared to be free for monomer assembly and disassembly. Our results indicate that ponticulin is a major membrane protein in Dictyostelium and that, in the proper lipid matrix, it is sufficient for lateral nucleation of actin assembly. To date, ponticulin is the only integral membrane protein known to directly nucleate actin polymerization.

Actins↗
PubMed1992

Diacylglycerol-stimulated formation of actin nucleation sites at plasma membranes.

Diacylglycerols, which are generated during phospholipase-catalyzed hydrolysis of phospholipids, stimulated actin polymerization in the presence of highly purified plasma membranes from the cellular slime mold Dictyostelium discoideum. The increased rate of actin polymerization apparently resulted from de novo formation of actin nucleation sites rather than uncapping of existing filament ends, because the membranes lacked detectable endogenous actin. The increased actin nucleation was mediated by a peripheral membrane component other than protein kinase C, the classical target of diacylglycerol action. These results indicate that diacylglycerols increase actin nucleation at plasma membranes and suggest a mechanism whereby signal transduction pathways may control cytoskeletal assembly.

Actins↗
PubMed1990

Ponticulin, a developmentally-regulated plasma membrane glycoprotein, mediates actin binding and nucleation.

Ponticulin is a 17,000-dalton transmembrane glycoprotein that is involved in the binding and nucleation of actin filaments by Dictyostelium discoideum plasma membranes. The major actin-binding protein isolated from these membranes by F-actin affinity chromatography, ponticulin also binds F-actin on blot overlays. The actin-binding activity of ponticulin in vitro is identical to that observed for purified plasma membranes: it resists extraction with 0.1 N NaOH, is sensitive to high salt concentrations, and is destroyed by heat, proteolysis, and thiol reduction and alkylation. A cytoplasmic domain of ponticulin mediates binding to actin because univalent antibody fragments directed against the cytoplasmic surface of this protein inhibit 96% of the actin-membrane binding in sedimentation assays. Antibody specific for ponticulin removes both ponticulin and the ability to reconstitute actin nucleation activity from detergent extracts of solubilized plasma membranes. Levels of plasma membrane ponticulin increase 2- to 3-fold during aggregation streaming, when cells adhere to each other and are highly motile. Although present throughout the plasma membrane, ponticulin is preferentially localized to some actin-rich membrane structures, including sites of cell-cell adhesion and arched regions of the plasma membrane reminiscent of the early stages of pseudopod formation. Ponticulin also is present but not obviously enriched at phagocytic cups of log-phase amebae. These results indicate that ponticulin may function in vivo to attach and nucleate actin filaments at the cytoplasmic surface of the plasma membrane. A 17,000-dalton analogue of ponticulin has been identified in human polymorphonuclear leukocyte plasma membranes by immunoblotting and immunofluorescence microscopy.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗
PubMed1990

Dictyostelium discoideum plasma membranes contain an actin-nucleating activity that requires ponticulin, an integral membrane glycoprotein.

In previous equilibrium binding studies, Dictyostelium discoideum plasma membranes have been shown to bind actin and to recruit actin into filaments at the membrane surface. However, little is known about the kinetic pathway(s) through which actin assembles at these, or other, membranes. We have used actin fluorescently labeled with N-(1-pyrenyl)iodoacetamide to examine the kinetics of actin assembly in the presence of D. discoideum plasma membranes. We find that these membranes increase the rate of actin polymerization. The rate of membrane-mediated actin polymerization is linearly dependent on membrane protein concentrations up to 20 micrograms/ml. Nucleation (the association of activated actin monomers into oligomers) appears to be the primary step of polymerization that is accelerated. A sole effect on the initial salt-induced actin conformational change (activation) is ruled out because membranes accelerate the polymerization of pre-activated actin as well as actin activated in the presence of membranes. Elongation of preexisting filaments also is not the major step of polymerization facilitated by membranes since membranes stripped of all peripheral components, including actin, increase the rate of actin assembly to about the same extent as do membranes containing small amounts of endogenous actin. Acceleration of the nucleation step by membranes also is supported by an analysis of the dependence of polymerization lag time on actin concentration. The barbed ends of membrane-induced actin nuclei are not obstructed by the membranes because the barbed end blocking agent, cytochalasin D, reduces the rate of membrane-mediated actin nucleation. Similarly, the pointed ends of the nuclei are not blocked by membranes since the depolymerization rate of gelsolin-capped actin is unchanged in the presence of membranes. These results are consistent with previous observations of lateral interactions between membranes and actin filaments. These results also are consistent with two predictions from a model based on equilibrium binding studies; i.e., that plasma membranes should nucleate actin assembly and that membrane-bound actin nuclei should have both ends free (Schwartz, M. A., and E. J. Luna. 1988. J. Cell Biol. 107:201-209). Integral membrane proteins mediate the actin nucleation activity because activity is eliminated by heat denaturation, treatment with reducing agents, or proteolysis of membranes. Activity also is abolished by solubilization with octylglucoside but is reconstituted upon removal or dilution of the detergent. Ponticulin, the major actin-binding protein in plasma membranes, appears to be necessary for nucleation activity since activity is not reconstituted from detergent extracts depleted of ponticulin.

Actins↗
PubMed1987

Binding of [14,15-3H]14,15-dihydroforskolin to rat liver membranes: comparison with the stimulatory effect of forskolin on adenylate cyclase.

The binding of [14,15-3H]14,15-dihydroforskolin ([3H]DHF) to rat liver membranes has been further characterized and was compared with the stimulatory effect of forskolin on adenylate cyclase. The binding equilibrium dissociation constant (KD) for 14,15-dihydroforskolin obtained in inhibition experiments was 0.6 microM, with a maximal binding capacity (Bmax) of 114 pmol/mg protein. A similar KD value (0.5 microM) was derived from kinetics studies that revealed very rapid association and dissociation reactions. For structure-activity relationship studies several forskolin derivatives were synthesized and tested for their ability to inhibit [3H]DHF binding and increase adenylate cyclase activity. Among the tested compounds, forskolin itself was the most potent agonist (K1 = 0.2 microM). Further modification of the molecule in position 7 and (or) 1 decreased or abolished its agonist properties in both adenylate cyclase and binding studies. [3H]DHF binding was not affected by several nucleotides, carbohydrates, lectins, and hormone receptor agonists including isoproterenol, glucagon, and adenosine, but the steroids 17-beta-estradiol, progesterone, and testosterone showed slight inhibitory effects at unphysiologically high concentrations. [3H]DHF binding and forskolin-stimulated adenylate cyclase were sensitive to heat and N-ethylmaleimide treatment. Forskolin protected adenylate cyclase against inactivation by heat but not by N-ethylmaleimide. Preincubation of the membrane with trypsin decreased [3H]DHF binding. The results presented in this study demonstrate that the binding sites identified with [3H]DHF have a high specificity for forskolin and provide evidence that these binding sites are involved in the stimulation of adenylate cyclase by forskolin.

Adenylyl Cyclases↗