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Biomedical subjects

F Rashid

Publications and source records attributed to F Rashid.

16 recordsLinked to original sources
PubMed2006

Studies on low molecular mass phytocystatins purified from Phaseolus mungo (Urd).

In the present study two phytocystatins (thiol protease inhibitors) have been isolated and purified to homogeneity from Phaseolus mungo by a simple two-step procedure using ammonium sulfate fractionation and gel filtration on Sephacryl-100 HR. The latter procedure yielded two peaks of the inhibitors (PMC I and PMC II). The pH optimum of both phytocystatins was pH 7.0; the temperature optima for PMC I and PMC II were 65 and 70 degrees C, respectively. The molecular masses of the purified phytocystatins were 19 and 17 kD, respectively, as determined by SDS-PAGE and mass spectrometry. Antibodies raised against the purified cystatins gave a single precipitin line in Ouchterlony double immunodiffusion. Kinetics of inhibition showed that PMC I and PMC II strongly inhibit papain and ficin but not trypsin and chymotrypsin. Binding stoichiometry of PMC I and PMC II with both papain and ficin was 1 : 2. The effect of urea on PMC I and PMC II was analyzed by fluorescence and circular dichroism spectroscopy. The CD results suggest an unfolding of PMC I and PMC II accompanying a decrease in the amount of extended (hydrated) coil structure and an increase in sheet-like structure. FTIR results show that PMC I is structurally similar to PMC II. Hydrophobic interactions are observed over a long time scale (5-150 min). Furthermore, fluorescence spectroscopy results were found to be in accordance with CD results, by showing quenching of fluorescence intensity of PMC I and PMC II, although to different extents, due to perturbations of the environment of aromatic residues in the protein. Both cystatins showed strong inhibitory activity against Escherichia coli and Staphylococcus aureus.

Circular Dichroism↗
PubMed2006

Effect of polyols and salts on the acid-induced state of human placental cystatin.

Polyols (glycerol and sorbitol) and salts (magnesium sulfate, sodium sulfate, and magnesium chloride) have been used to study the refolding of the acid-induced state of human placental cystatin (HPC), which is a low molecular weight (12,500 daltons) thiol proteinase inhibitor, in terms of CD spectroscopy, binding of hydrophobic dye 1-anilinonaphthalene-8-sulfonic acid (ANS), and intrinsic fluorescence measurements. The helical content of acid-denatured HPC increased with increase in glycerol concentration (0-80%). At 80% glycerol concentration, the secondary structural features observed in the far UV-CD region are similar to those of the native state (pH 6.0). The intrinsic fluorescence and near UV-CD studies showed that this 80% glycerol-induced state has a significant amount of tertiary structure with decreased ANS binding compared to the acid-denatured state. It was found that glycerol is more effective in stabilizing the acid-denatured state of HPC as compared to sorbitol. Among salts the stability effect was more for MgCl(2) (used up to concentration of 3 M) compared to MgSO(4) and Na(2)SO(4) (used up to the concentration of 1.5 M due to restricted solubility of HPC at higher sulfate salt concentrations) as determined by CD studies and fluorescence measurements, which showed secondary and tertiary structural resemblance of this MgCl(2)-induced state close to native state and showed overall spectral features in between the native state and the acid-denatured state. This MgCl(2) (3 M)-induced state showed decreased ANS fluorescence as compared to the acid-denatured state but more than that of the native state. The results taken together suggest that the acid-denatured state of HPC in the presence of 80% glycerol or 3 M MgCl(2) has a conformation in between that of the native state (pH 6.0) and the acid-induced state at pH 2.0.

Circular Dichroism↗
PubMed2005

Detailed biochemical characterization of human placental cystatin (HPC).

A low molecular weight thiol protease inhibitor (12,500) purified from human placenta has been characterized in detail. Human placental cystatin (HPC) was found to be stable in the pH range 3.0-9.0 and temperature stability was between 40 and 100 degrees C. It does not have any disulphide groups and carbohydrate content. There was no cross-reaction between anti-HPC serum and other purified cystatins like HMW kininogens isolated from sheep plasma and phytocystatins isolated from Phaseolus mungo. The kinetics of inhibition of HPC was studied with ficin and bromelain and the comparison was made with our already reported results with papain. The respective K(i) values obtained for ficin and bromelain are 8.4 x 10(-8) M and 9.5 x 10(-8) M, respectively, whereas the value for papain was 5.5 x 10(-8) M. The values of association constants (K(ass)) for ficin and bromelain were 2.9 x 10(3) and 8.6 x 10(2) M(-1) s(-1), respectively, however, the value for papain was 3.4 x 10(4) M(-1) s(-1), the respective dissociation constant values for ficin and bromelain were 2.6 x 10(-5) and 2.1 x 10(-5) s(-1), respectively, and the value obtained for papain was 2.3 x 10(-5) s(-1). These kinetic parameters taken together along with t(1/2) values and IC(50) values imply that HPC binds more effectively to papain, then ficin and least with bromelain. Far-UV-CD analysis shows that HPC has 21.08% alpha-helical structure and significant amount of beta structure. Near-UV-CD spectra of HPC show positive peak at 280 nm indicating significant amount of tertiary interactions. The partial amino acid sequence analysis shows that HPC has highest sequence homology with chicken cystatin and Gly residue is present at position 11 rather than at conserved position 9, which has also been reported for human stefin A structure. The hydropathy plot of 1-30 amino acid residues shows that most amino acids of this stretch are present in the hydrophobic core of the protein. Owing to low molecular weight, absence of disulphide bonds and carbohydrate content HPC can be placed in type I cystatin family with some resemblance to chicken cystatin as shown by CD studies and amino acid sequence analysis.

Amino Acid Sequence↗
PubMed2003

Complementary studies of the gastrointestinal safety of the cyclo-oxygenase-2-selective inhibitor etoricoxib.

BACKGROUND: Cyclo-oxygenase-2-selective non-steroidal anti-inflammatory drugs are intended to preserve cyclo-oxygenase-1-mediated gastroprotection and platelet function, whilst inhibiting cyclo-oxygenase-2-mediated inflammation. AIM: To assess the gastrointestinal safety of the cyclo-oxygenase-2-selective inhibitor etoricoxib vs. non-selective non-steroidal anti-inflammatory drugs. METHODS: Two randomized, double-blind, placebo- and active-controlled studies were performed: (i) daily faecal red blood cell loss was measured in 62 subjects receiving etoricoxib (120 mg once daily), ibuprofen (800 mg t.d.s.) or placebo for 28 days; (ii) the incidence of endoscopically detectable gastric/duodenal ulcers was determined in 742 osteoarthritis or rheumatoid arthritis patients receiving etoricoxib (120 mg once daily), naproxen (500 mg b.d.) or placebo over 12 weeks. RESULTS: In the first study, the between-treatment ratio of faecal blood loss for etoricoxib vs. placebo (1.06) was not significantly different from unity; however, the ratios for ibuprofen vs. placebo (3.26) and etoricoxib (3.08) were significantly greater than unity (P < 0.001). In the second study, the incidence of ulcers of > or = 3 mm with naproxen (25.3%) was significantly higher than that with etoricoxib (7.4%) or placebo (1.4%; P < 0.001); the results were similar for ulcers of > or = 5 mm. CONCLUSIONS: The reduced toxicity of etoricoxib (less faecal blood loss and fewer endoscopically detectable lesions) suggests that use of this drug will may be associated with a reduced incidence of gastrointestinal perforations, ulcers and bleeds.

Adolescent↗
PubMed2002

Changing face of adult coeliac disease: experience of a single university hospital in South Yorkshire.

OBJECTIVE: To determine the incidence and presenting features of adult coeliac disease in a single university hospital in South Yorkshire. DESIGN: A retrospective case finding study. Data were obtained from pathology and immunology databases, clinical notes, dietetic records, and patient questionnaires. SETTING: Royal Hallamshire Hospital in South Yorkshire, England. PARTICIPANTS: All recorded cases of coeliac disease. MAIN OUTCOME MEASURES: Crude annual incidence rates for coeliac disease was obtained. The numbers of coeliac antibody profiles requested per year from the Royal Hallamshire Hospital were ascertained. Age at diagnosis, sex, year of diagnosis, presenting symptoms, associated conditions, and delay in diagnosis was documented. In addition the specialty of the clinician who made the diagnosis was noted. RESULTS: There were 264 cases in total (male n=86, ratio 1:2). Mean age at diagnosis was 44.9 years (range 1-82, median 44.5). A trend was observed from 1990 to 2000 inclusive, of an annual increase in the incidence of coeliac disease. There has been a coincidental increase in the measurement of associated antibodies. Although 28.4% of patients presented with gastrointestinal symptoms, 20.1% had iron deficiency anaemia. The ratio of typical to atypical symptoms was 1:2.5. (single sample test of proportions p<0.001). The diagnosis was made by a gastroenterologist in only 52.7% of cases. The median duration of symptoms before the diagnosis of coeliac disease was 4.9 years (range 0.25-16 years). CONCLUSION: Coeliac disease is now presenting more commonly without gastrointestinal symptoms and often to specialties other than gastroenterology. Although more cases are diagnosed, this may be a reflection of increasing recognition rather than a true increase in incidence.

Adolescent↗
PubMed2000

An alternative approach to the management dilemma of the mildly dyskaryotic smear based on audit of outcome.

We describe a study which takes an alternative approach to the management dilemma of the mildly dyskaryotic cervical smear. Two hundred and fifty women with a smear showing mild dyskaryosis were studied by auditing the clinical outcome as well as the cost. The cost of providing the colposcopy services during the index year was approximately pounds sterling 70000 for an average size district general Hospital. The proportion of women managed by the current guidelines and avoiding colposcopy after a first mildly dyskaryotic smear was only 30%. The majority of patients will eventually have colposcopy despite a policy of cytological surveillance. The alternative approach, to offer colposcopy immediately after the first mildly dyskaryotic smear, would result in a small increase in cost for our unit, equivalent to one extra colposcopy patient per week.

Colposcopy↗
PubMed2000

Mental health team leadership and consumers satisfaction and quality of life.

OBJECTIVE: The purpose of this study was to determine the association between leadership styles of leaders of mental health treatment teams and consumers' ratings of satisfaction with the program and their quality of life. METHODS: A multifactor model has distinguished three factors relevant to leadership of mental health teams: transformational leadership, in which a leader's primary goal is to lead the team to evolving better programs; transactional leadership, in which the leader strives to maintain effective programs through feedback and reinforcement; and laissez-faire leadership, an ineffective, hands-off leadership style. Research has shown transformational leadership to be positively associated with measures of the team's functioning, but the effects of leadership style on consumers is not well known. A total of 143 leaders and 473 subordinates from 31 clinical teams rated the leadership style of the team leader. In addition, 184 consumers served by these teams rated their satisfaction with the treatment program and their quality of life. RESULTS: Consumers' satisfaction and quality of life were inversely associated with laissez-faire approaches to leadership and positively associated with both transformational and transactional leadership. Moreover, leaders' and subordinates' ratings of team leadership accounted for independent variance in satisfaction ratings-up to 40 percent of the total variance. CONCLUSIONS: Leadership seems to be an important variable for understanding a team's impact on its consumers.

Adult↗
PubMed1999

The construct validity of empowerment among consumers of mental health services.

Subscales of the Empowerment Scale (Rogers, E. S., Chamberlin, J., Ellison, M. L., Crean, T., 1997. A consumer-constructed scale to measure empowerment among users of mental health services. Psychiatr. Serv. 48, 1042-1047) were examined to see whether they fit a model of consumer empowerment that distinguishes self- and community orientations. In addition, the relationship of these two superordinate factors to several psychosocial factors was examined. Thirty-five participants in a partial hospitalization program were administered the Empowerment Scale and measures of quality of life, social support, self-esteem, psychiatric symptoms, needs and resources, global functioning, and verbal intelligence. Analysis of the subscales of the Empowerment Scale yielded two factors consistent with self- and community orientations to empowerment. Correlational analyses revealed that the two superordinate factors were associated with different sets of psychosocial variables. A self-orientation to empowerment was significantly associated with quality of life, social support, self-esteem, and psychiatric symptoms. Community orientation was correlated with self-esteem, resources, verbal intelligence, and ethnicity. The implications of these findings for a model of consumer empowerment are discussed.

Adult↗
PubMed1999

Recovery as a psychological construct.

Mental health advocates have proposed recovery as a vision for severe mental illness. The purpose of this study is to examine psychometric characteristics of a measure of the psychological construct. Thirty-five participants in a partial hospitalization program were administered the Recovery Scale and measures of quality of life, social support, self-esteem, consumer empowerment, psychiatric symptoms, needs and resources, global functioning, and verbal intelligence. Results showed the scale to have satisfactory test-retest reliability and internal consistency. Analysis of the concurrent validity of the Recovery Scale showed recovery to be positively associated with self-esteem, empowerment, social support, and quality of life. It was inversely associated with psychiatric symptoms and age. Implications of these findings for a psychological model of recovery are discussed.

Adult↗
PubMed1996

Efficiency of aerosol medication delivery from a metered dose inhaler versus jet nebulizer in infants with bronchopulmonary dysplasia.

The best means for optimal delivery of drugs into lungs of infants with bronchopulmonary dysplasia (BPD) is uncertain. We aimed to measure radio-aerosol deposition of salbutamol by jet nebulizer and metered dose inhalers (MDI) in ventilated and non-ventilated BPD infants. In a randomized, crossover sequence, salbutamol lung deposition was measured using an MDI (2 puffs or 200 micrograms) or sidestream jet nebulizer (5 minutes of nebulization with 100 micrograms/kg) in 10 ventilated (mean birthweight, 1,101 g) and 13 non-ventilated (mean birthweight, 1,093 g) prematurely born infants. Non-ventilated infants inhaled aerosol through a face mask, connected to a nebulizer or an MDI and spacer (Aerochamber). Ventilated infants received aerosol from an MDI + MV15 Aerochamber or a nebulizer inserted in the ventilator circuit. Lung deposition by both methods was low: mean (SEM) from the MDI was 0.67 (0.17)% of the actuated dose, and from the nebulizer it was 1.74 (0.21)% and 0.28 (0.04)% of the nebulized and initial reservoir doses, respectively. Corresponding figures for the ventilated infants were 0.98 (0.19)% from the MDI and 0.95 (0.23)% and 0.22 (0.08)% from the nebulizer. In both groups, and for both methods of delivery, there was marked inter-subject variability in lung deposition and a tendency for the aerosol to be distributed to the central lung regions.

Aerosols↗
PubMed1991

Predicting the behaviour and selectivity of fluorescent probes for lysosomes and related structures by means of structure-activity models.

Cultured rat fibroblasts were exposed to 50 fluorescent probes of varied physicochemical characteristics. Probe concentrations, fluorochrome excitation wavelength and period of illumination, and cell-probe contact time were varied. Structure-activity relationships defining a number of classes of fluorescent probes for lysosomes and related processes and compartments were demonstrated. Numerical specifications are now available for several familiar classes of probes: (a) acidotropic weak bases, used as markers for low pH compartments; (b) markers of adsorptive pinocytosis, involving non-specific protein binding; (c) markers for fluid phase pinocytosis; and (d) viability stains involving intralysosomal enzymic activity. Two novel classes of probes have also been specified numerically: (a) acid-precipitated weak acids, as markers for low pH compartments; and (b) lipid-binding markers of adsorptive pinocytosis. Overall, these structure-activity models provide a tool for predicting whether or not compounds enter cells; and whether they accumulate in lysosomes and related compartments. Pathways of entry are also predicted. This tool should permit design and selection of improved probes, and provide a better understanding of existing reagents. Moreover these models are expected to be applicable to interactions between any non-polymeric xenobiotic with lysosomes and related compartments.

Animals↗
PubMed1991

Accumulation of fluorescent non-cationic probes in mitochondria of cultured cells: observations, a proposed mechanism, and some implications.

Cultured rat fibroblasts were exposed to millimolar concentrations of forty-four non-cationic fluorescent probes, of very varied physico-chemical properties. Mitochondrial staining occurred with nineteen of these probes, nine of which were nominally anionic and ten nominally non-ionic. All nineteen were in fact lipophilic weak acids. Using structural parameters these could be specified numerically as follows: electric charge less than or equal to 0; log P (less-ionized form) less than 0; and pKa approximately 7. In addition to these structural variables, dye concentration and the time of exposure of cells to probes were significant factors for the staining of mitochondria. Accumulation of these compounds can be understood in terms of ion-trapping of hydrophilic salts of lipophilic weak acids, due to the internal pH of respiring mitochondria being higher than the cytosolic pH. As a case example of the application of this approach, the mode of action of many inhibitors of mitochondrial anabolism is discussed in terms of the mechanisms introduced here.

Animals↗
PubMed1990

Interaction of molecular probes with living cells and tissues. Part 2. A structure-activity analysis of mitochondrial staining by cationic probes, and a discussion of the synergistic nature of image-based and biochemical approaches.

Cultured rat fibroblasts were exposed to 41 cationic fluorescent probes of very varied hydrophilicity/lipophilicity. Outcome of probe-cell interaction fell into one of the following categories: probe failed to enter the cells; probe accumulated on cell surfaces; probe accumulated in mitochondria, and/or in other intracellular regions. The observations were analysed using a Simplistic Chinese Box (SCB) approach, and the following conclusions were reached. It was the hydrophilic probes which failed to enter cells, whilst extremely lipophilic probes were retained on the cell surfaces. Only the slightly lipophilic cationic probes were permeant, and accumulated in mitochondria. Using the probes log P values to model hydrophilicity/lipophilicity, effective cationic mitochondrial stains can be specified numerically so: 0 less than log P probe less than +5. This SCB model was used to rationalise a variety of earlier observations on the action of mitochondrial probes. The applicability of the SCB approach to integrate image-based and biochemical investigations was demonstrated by using the action of chlorpromazine on mitochondrial action as a case example.

Animals↗
PubMed1990

Interactions of molecular probes with living cells and tissues. Part 1. Some general mechanistic proposals, making use of a simplistic Chinese box model.

A simple and generalised model-termed the simplistic Chinese box [SCB] model-for the interaction of molecular probes with living systems is described. The SCB model includes the following assumptions. That living systems may be considered as built from biologically defined boxes, e.g. whole cell, nucleus, nucleoli. That movement of molecular probes into and through these boxes is strongly influenced by box wall permeability, which in turn is largely dependent on the simple physicochemical properties of probe and wall. That retention of probes in boxes is influenced by permeability of the walls and by trapping of probes by boxes and walls, the latter effect also being strongly dependent on simple physicochemical properties. That important physicochemical properties include electric charge, hydrophilicity/lipophilicity, non-specific protein binding, and molecular size. That, since all these factors can be expressed or modelled numerically, SAR methodology is an appropriate technique for analysing molecular probe investigations.

Biological Transport↗