Coinheritance of alpha-and beta-spectrin gene mutations in a case of hereditary elliptocytosis.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
M J King
Publications and source records attributed to M J King.
Elevated expression of the cdc25A protein phosphatase in colon cancer.
The nuclear protein phosphatase cdc25A has been postulated to be a protooncogene. The total nuclear phosphotyrosyl protein phosphatase (PTP) activity and the expression of cdc25A were compared in normal and cancerous colon epithelial tissue. Nuclei derived from normal mucosal epithelium and tumors were analyzed for phosphotyrosyl protein phosphatase activity using the malachite green assay and a synthetic phosphotyrosyl peptide based on the sequence of cdc2, a known cdc25A phosphotyrosyl protein substrate. Tumorigenesis resulted in elevated nuclear PTP activity (343.0 +/- 37.0% of normal epithelial PTP activity) in 52% (29 of 56) of colon tumors. In all cases elevated nuclear PTP activity correlated with an increase in the expression of cdc25A. The changes in PTP activity observed were not due to any increase in the rate of growth of the colonic mucosa as no corresponding changes occurred with PTP activity under conditions of rapid mucosal growth.
Animals↗
Community residential program policies, services, and treatment orientations influence patients' participation in treatment.
The study sought to identify community residential program characteristics that predict patients' participation in treatment and to examine the association between these characteristics, participation, and outcomes at discharge from treatment. A sample of 2,790 patients with substance abuse disorders was assessed at entry into and discharge from 87 community residential facilities (CRFs). The CRFs were assessed using a survey that obtained information about program size and staffing, policies and services, and treatment orientation. High expectations for patients' functioning, clear policies, structured programming, a high proportion of staff in recovery from substance abuse problems, and more emphasis on psychosocial treatment were associated with patients' participation in program services and activities. Higher expectations for functioning and a strong treatment orientation enhanced participation more among better functioning patients; program support and structure enhanced participation more among impaired patients. Participation in treatment independently predicted outcomes at discharge even after both patient and program characteristics were controlled. These findings show that community residential program policies, services, and treatment orientations play a key role in influencing patients' engagement in treatment, which, in turn, improves patients' outcomes at discharge.
Adult↗
Three-dimensional study of the effect of two leaflet opening angles on the time-dependent flow through a bileaflet mechanical heart valve.
A three-dimensional (3-D), time-dependent computational fluid dynamics (CFD) model was used to investigate the effect of leaflet opening angle on the flow through a fully open bileaflet heart valve up to peak systole. A laminar flow model of a Newtonian fluid was used, and the peak systolic. Reynolds number was 1500, based on the aortic radius and the average velocity at peak systole. This resulted in a Reynolds number of 5800, based on the aortic radius and the local maximum velocity. The flow fields through and downstream of the bileaflet valves were complex, with strong time-dependent 3-D vortices being found in planes parallel and perpendicular to the leaflets. The parametric study of the effect of leaflet opening angle showed that, as the leaflet opening angle increased from 78 degrees to 85 degrees, the flow downstream of the valve leaflets became more centralized, and the wake downstream of the leaflet decreased in size. However, as the opening angle increased from 78 degrees to 85 degrees, the maximum shear rate and the maximum velocity increased, suggesting that the design of the central orifice geometry was also an important consideration.
Biophysical Phenomena↗
Co-presence of a point mutation and a deletion of exon 3 in the glycophorin C gene and concomitant production of a Gerbich-related antibody.
BACKGROUND: Antigens of the human blood group system Gerbich (Ge) are located on sialoglycoproteins glycophorin C (GPC) and glycophorin D (GPD). CASE REPORT: The Ge+ proposita (RW) produced an alloanti-Ge after receiving 2 units of red cells (RBCs) during surgery. Further studies were carried out to characterize the antibody specificity, RBC GPC and/or GPD (GPC/GPD), and the glycophorin C gene (GYPC) from RW and her compatible siblings. RW's serum contained an alloanti-Ge that did not react with RBCs from RW or four of her siblings or with RBCs with Ge-negative phenotypes. An eluate of RW's antibody reacted weakly with GPC in Western blotting. RW's RBCs were positive with 20 alloanti-Ge2, 1 autoanti-Ge2, 4 alloanti-Ge3, and 1 alloanti-Ge4. Titrations revealed weak expression of these antigens on her RBCs and those of her compatible siblings as compared with controls. In contrast, titrations of mouse and rat monoclonal antibodies specific for GPC/GPD showed no differences. Western blotting of RBC membranes using GPC/GPD specific monoclonal antibodies showed a broad diffuse band corresponding to GPC.Ge in addition to GPC and GPD. Blotting of membranes from trypsin-treated RBCs from these individuals revealed an increase of 1500 in M(r) of membrane-bound tryptic fragment over that in the membranes from typsin-treated RBCs from persons with normal GPC/GPD. In RT-PCR, two products were obtained for RW and her compatible siblings: one had a complete deletion of exon 3 and the other had a base change (A-->T) in nucleotide 173 in exon 3 (confirmed by genomic DNA sequencing of exon 3). This point mutation has resulted in the loss of restriction enzyme Tth111 I-sensitive site in the mutant GYPC. CONCLUSION: The specificity of antibody in RW's serum was serologically anti-Ge2. Two genetic events occurred in exon 3 in GYPC of RW and her compatible siblings. The exon 3 deletion confirmed a Ge:-2,-3,4 haplotype. The abnormal tryptic fragment obtained was due to the (A173-->T) base change in exon 3 that resulted in Asp58-->Val in the deduced amino acid sequence at the membrane boundary.
Animals↗
Correlations between short-course triathlon performance and physiological variables determined in laboratory cycle and treadmill tests.
The aim of this study was to investigate the relationships between physiological variables measured in graded cycling (CM) and treadmill running (RM) maximal tests and the performance of a short-course triathlon (1 km swim, 30 km cycling and 8 km running) in recreational triathletes. Ten male athletes with mean (+/-SD) age of 27.4(+/-5.7) years and maximal oxygen consumption (VO2peak) of 63.3(+/-8.95) mL.kg-1.min-1 participated in the study. The results showed that the VO2peak and VO2 at ventilatory threshold (VO2VT) determined in CM were significantly correlated to the overall and running times of the triathlon (r = -0.64 - 0.77, p < or = 0.05). The VO2peak and VO2VT determined in RM were also correlated to the running time when expressed as mL.kg-1.min-1 (r = -0.73, p < or = 0.05). The VT expressed as %VO2peak in both tests showed no significant correlations to triathlon performance. It appears that it is the absolute aerobic capacity of these athletes being critical to maintain a high exercise intensity in the triathlon, especially during the running segment. The mean heart rate (HR) measured in four subjects during the cycling and running segments of the triathlon was similar to the HR at VT determined in CM, which indicated that these athletes could maintain an exercise intensity close to the VT level during the competition. There was no significant correlation found between the swimming time and physiological variables measured in the laboratory cycling and running tests, which could be explained by the specific skills and economy of movement required in these exercises.
Adult↗
Dermatologic problems in podiatric sports medicine.
The podiatric physician should be keenly aware of various skin conditions and how to deal with them. Dermatologic conditions can be a significant deterrent to the athlete and his or her training schedule.
Foot Diseases↗
Structural features of crayfish phasic and tonic neuromuscular terminals.
We examined the fine structure of terminals of the phasic and tonic excitatory axon to the crayfish limb extensor muscle. The phasic terminals are known to release 50-100 times more transmitter for a small length of terminal for a single impulse. Phasic terminals labeled with horseradish peroxidase (HRP) were relatively thin and contained a single unbranched mitochondrion; tonic terminals were much thicker, and their varicosities contained several multibranched mitochondria. Tonic terminals devoted a larger proportion of their total volume to mitochondria. The percentage volume of clear synaptic vesicles was slightly higher in phasic axon terminals, but as the tonic axon terminals were fivefold larger in volume, the total synaptic volume is much greater in tonic than phasic terminals. The number of synapses per length of terminal, and the total number of active zones per length of terminal, were greater for tonic terminals, and individual synapses were, on average, slightly larger in surface contact area for tonic terminals. In contrast, individual active zones were, on average, longer in phasic synapses. A higher proportion (50%) of phasic synapses had multiple active zones than was the case for tonic synapses (16%), and pairs of closely spaced active zones were more frequently found on phasic synapses. These findings clearly rule out synapse and active zone number as a factor contributing to higher transmitter output, but suggest that active zone size and synaptic complexity, as evidenced by multiple closely spaced active zones in a single synapse, are likely to play a causal role in the greater transmitter release of the phasic terminal. Even synapse complexity would not be enough to account fully for the large difference in terminal transmitter output, and additional factors may include electrical and biochemical differences.
Animals↗
A three-dimensional, time-dependent analysis of flow through a bileaflet mechanical heart valve: comparison of experimental and numerical results.
The flow through a bileaflet mechanical heart valve during the first half of systole was predicted using computational fluid dynamics (CFD). A three-dimensional model of the geometry of the ventricle, valve, sinus and aorta was developed. Flow through the valve was assumed to be Newtonian and laminar. The peak systolic Reynolds number was 1500 based on the aortic radius and the mean aortic velocity. Flow visualisation and laser Doppler anemometry (LDA) experiments were performed and the results were compared to the CFD model. Good agreement between the LDA measurements and CFD predictions was found in the jets through the major orifices of the valve. The global flow fields predicted by the CFD showed reasonable agreement with the flow visualisation. A starting vortex was shed from the valve leaflets of the CarboMedics valve and the prototype valve. As systole progressed the two major orifice jets were directed towards the aortic wall and a weaker central jet was seen in both the experimental and CFD models. Large vortices were present on either side of the central orifice jet in the sinus area of both models. The three-dimensional time-dependent CFD model was considered to give a reasonable indication of the dominant flow patterns downstream of the bileaflet heart valve and has the potential to be an extremely useful tool to analyse the different designs of existing and future bileaflet valves.
Aorta↗
Tyrosine dephosphorylation in the gut.
Explore the source record for details and available documents.
Animals↗
Outcomes of residential treatment of substance abuse in hospital- and community-based programs.
OBJECTIVE: The study sought to determine whether inpatient readmission rates differed for patients with substance use disorders who were treated in either hospital-based or community-based transitional residential care. Length of residential care and intensity of outpatient mental health aftercare were examined as predictors of readmission. METHODS: Department of Veterans Affairs nationwide databases were used to document readmissions at one- and two-year intervals for male inpatients treated for substance use disorders who were discharged either to hospital-based (N = 2,190) or community-based (N = 4,490) residential care. Patients with and without concomitant psychiatric diagnoses were identified. RESULTS: Patients treated in community-based residential programs had lower one- and two-year readmission rates than patients who received hospital-based residential care. Longer episodes of residential care and more outpatient mental health care were also associated with lower readmission rates. Among patients with concomitant psychiatric disorders, those in hospital-based care benefited more from longer episodes of residential care and more intensive outpatient mental health aftercare. Residential care, longer episodes of care, and more outpatient mental health care were independent predictors of lower one- and two-year readmission rates after patient-based risk factors were controlled. CONCLUSIONS: The findings highlight the value of providing adequate amounts of residential and outpatient care for patients in substance abuse treatment, especially patients with concomitant psychiatric disorders.
Adult↗
Activity of asynchronous flight muscle from two bee families during sonication (buzzing).
The indirect flight muscles of bees are used to produce a variety of actions in addition to flight, including sonication, which has a higher frequency than flight. We observed the dynamic movement of the scutum during sonication and the transition from tethered flight to sonication. During sonication, the scutum oscillated above its rest position, indicating that the conformation of the structural components of the thorax had been altered. Sonication vibrations of the thorax occurred by deformation of the scutum rather than by opening of the scutal fissure and are smaller than vibrations associated with flight. During tethered flight, the ratio of muscle activity (recorded via electromyograms) between the dorsal longitudinal muscles and the dorsoventral muscles approached 1, but during sonication the ratio was significantly higher (up to 4.0). This increase may cause the dorsal longitudinal muscles to contract further than the dorsoventral muscles and close the scutal fissure during sonication, so limiting the displacement of the wings and 'decoupling' them from the indirect flight muscles.
Animals↗
Peritoneal dialysis in the Pacific.
Peritoneal dialysis (PD) in the Pacific is the predominant dialysis modality for home dialysis patients. Patient location, age, personal preference, and medical condition are all taken into consideration. However, with the steadily increasing number of patients on PD, financial constraints are now affecting the nurse-patient ratios. As a consequence, PD nurses are constantly seeking new and improved clinical practice regimes with which they can provide and maintain quality, cost-effective nursing care. To enable PD nurses to provide such care, they are now, more than ever, involved in patient, professional, and management issues. These patient issues include, but are not limited to: the elderly, the diabetic, the indigenous patient, and their carers, peritonitis, exit-site infection, and adequate dialysis. Professional issues include the development of standards of clinical practice, nursing research, quality improvement, and tertiary education. Management issues are constantly encroaching into the clinical practice setting, therefore the PD nurse must now justify spending, develop strategic plans, and meet annual budgets. In conclusion, it can be seen that PD nurses in the Pacific are faced with similar patient-care, professional, and management issues as their counterparts throughout the world.
Adolescent↗
An initial investigation into the wear and damage within the pivots of three types of bileaflet mechanical heart valves.
Two 29 mm St. Jude Medical valves, two 29 mm CarboMedics valves and two 29 mm Sorin Bicarbon valves were tested in a real time fatigue test rig. The test rig was run at 72 beats/min with a stroke volume of 70 ml for approximately one million cycles. Optical microscopy was used to investigate the valve surfaces. Possible deterioration of the surface finish was observed on the stops of the hinge recesses in the St. Jude Medical and CarboMedics valves. In the Sorin valves areas of the pyrolytic carbon coating was worn away adjacent to and on the valve stops.
Biocompatible Materials↗
Differential activation of bovine brain N-myristoyltransferase(s) by a cytosolic activator.
N-Myristoyltransferase (NMT) is an essential eukaryotic enzyme that catalyses the transfer of myristate from myristoyl-CoA to the NH2-terminal glycine residue of a number of important proteins of diverse function. Little is known about the control and regulation of NMT in higher eukaryotes. We have identified a N-myristoyltransferase activator (NAF45) which copurified with one form of bovine brain NMT activity which failed to bind to phosphocellulose column chromatography (NMT.PU) and represented 32 +/- 4% of the total NMT activity applied to this column. The NAF45 and NMT activities were resolved by mono Q column chromatography from the NMT.PU fraction. Resolution resulted in a loss of NMT.PU activity. NAF45 was a nondialysable molecule with an apparent molecular mass of 45 kDa. Reconstitution of the NAF45 and NMT resulted in the recovery of NMT activity, indicating that this form of NMT is dependent on the presence of NAF45. NAF45 was able to stimulate other forms of NMT activity (maximum of 3-4 fold) in a highly cooperative fashion (Hills coefficient of approximately 5.5). Stimulation was in terms of both the rate of myristoylation and the overall production of myristoylpeptide, indicating that the end point of the reaction was shifted in favour of myristoylpeptide production. NAF45 was able to compete with NIP71 for NMT [King, M.J. and Sharma, R.K. (1993) Biochem, J. 291, 635-639], although its affinity appeared lower than the NIP71.
Acyltransferases↗
The antifreeze protein genes of the winter flounder, Pleuronectus americanus, are differentially regulated in liver and non-liver tissues.
The synthesis of winter flounder (Pleuronectus americanus) antifreeze protein (AFP) mRNAs in the liver is seasonally regulated by the pituitary gland. With the recent discovery that AFP mRNAs are also present in several non-liver tissues, the aim of the present investigation was to compare the regulatory mechanisms of AFP genes in liver and non-liver tissues. Northern blot analyses indicate that the level of liver AFP mRNA undergoes a several hundred fold difference between the winter and summer months, while AFP mRNAs from gills and kidneys exhibit only a modest 5-10 fold seasonal variation. As expected, the liver AFP mRNA in the hypophysectomized fish was increased by over 40 fold. However, no significant increase was observed for the non-liver AFP mRNAs upon hypophysectomy. These investigations suggest that AFP mRNAs in liver and non-liver tissues are differentially regulated.
Animals↗
Reactivity with erythroid and non-erythroid tissues of a murine monoclonal antibody to a synthetic peptide having amino acid sequence common to cytoplasmic domain of human glycophorins C and D.
Three synthetic peptides encompassing the entire cytoplasmic polypeptide sequence (amino acid residues 82-128) of glycophorin C (GPC) and glycophorin D (GPD) were used to immunize mice for the production of monoclonal antibodies (MoAbs). Only the synthetic peptide (GPC-peptide-1) corresponding to C-terminal residues 112-128 elicited a MoAb (named BGRL-100) which could react with native and denatured GPC and GPD. We characterized BGRL-100 by inhibition using GPC-peptide 1 and red cell sialoglycoproteins. The ability of BGRL-100 to interact with native GPC and GPD was assessed by immunoprecipitation with normal red cells (RBCs), and with denatured GPC and GPD by Western blotting of both normal RBCs and RBCs carrying GPC variants. Immunohistochemical staining of human tissue sections was performed using both BGRL-100 and a rat MoAb (named BRAC-1), which is specific for an extracellular domain of GPC and GPD. Both antibodies showed strong staining of erythroid lineage haemopoietic cells in fetal liver, sinusoids of adult liver and RBCs in the blood vessels of all tissues tested. Neither antibody reacted with epithelia from a range of human tissues. However, both MoAbs stained neural tissue in a distinctive fibrillar pattern. This suggests the presence of an analogue of erythroid GPC in neural tissues.
Amino Acid Sequence↗
Mechanisms of action of NIP71 on N-myristoyltransferase activity.
N-Myristoyl-CoA:protein N-myristoyltransferase (NMT) is the enzyme that catalyses the transfer of myristate from myristoyl-CoA to the N-terminal glycine of protein substrates. NMT was highly purified from bovine brain by procedures involving sequential column chromatography on DEAE-Sepharose CL-6B, phosphocellulose, hydroxylapatite, and mono S and mono Q f.p.l.c.. The highly purified NMT (termed NMT.II) possessed high specific activity with peptide substrates derived from the N-terminal sequences of the cAMP-dependent protein kinase and pp60src (29,800 and 47,600 pmol N-myristoylpeptide formed/min/mg, respectively), intermediate activity with a peptide based on the N-terminal sequence of a viral structural protein (microliter) (M2; 17,300 pmol N-myristoylpeptide formed/min/mg) and very low activity with a peptide derived from the N-terminal sequence of myristoylated alanine-rich C-kinase substrate (MARCKS; 1500 pmol myristoylpeptide formed/min/mg). An NMT protein inhibitor (NIP71) isolated from the particulate fraction of bovine brain (King MJ and Sharma RK: Biochem J 291:635-639, 1993) potently inhibited highly purified NMT activity (IC50 23.7 nM). A minor NMT activity (NMT.PU; 30% total NMT activity), which failed to bind to phosphocellulose, was insensitive to NIP71 inhibition. Inhibition of NMT was observed to be via mixed inhibition with respect to both the myristoyl-CoA and peptide substrates with NIP71 having an apparent higher affinity for NMT than the NMT.myristoyl.CoA complex. Inhibition by NIP71 at subsaturating concentrations of myristoyl-CoA and peptide resulted in a sigmoidal pattern of inhibition indicating that bovine brain possesses a potent and delicate on/off switch to control NMT activity.
Acyltransferases↗