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Biomedical subjects

C Hall

Publications and source records attributed to C Hall.

At least 109 records · Page 6Linked to original sources

Rapid hyaluronan uptake is associated with enhanced motility: implications for an intracellular mode of action.

Texas red-labeled hyaluronan (TR-HA) is rapidly taken up in a CD44 independent manner into ras-transformed 10T1/2 fibroblasts, where it accumulates in both cell ruffles/lamellae, the perinuclear area, and the nucleus. HA does not accumulate in the cell ruffles/lamellae of parental 10T1/2 cells. Addition of HA to ras-transformed cells promotes their random motility but has no effect on 10T1/2 cell motility. 10T1/2 cells can be modified to take up HA into cell ruffles by exposure to phorbol ester or direct microinjection of HA into cells. Both treatments significantly stimulate 10T1/2 cell motility.

Animals↗

PAK promotes morphological changes by acting upstream of Rac.

The serine/threonine kinase p21-activated kinase (PAK) has been implicated as a downstream effector of the small GTPases Rac and Cdc42. While these GTPases evidently induce a variety of morphological changes, the role(s) of PAK remains elusive. Here we report that overexpression of betaPAK in PC12 cells induces a Rac phenotype, including cell spreading/membrane ruffling, and increased lamellipodia formation at growth cones and shafts of nerve growth factor-induced neurites. These effects are still observed in cells expressing kinase-negative or Rac/Cdc42 binding-deficient PAK mutants, indicating that kinase- and p21-binding domains are not involved. Furthermore, lamellipodia formation in all cell lines, including those expressing Rac binding-deficient PAK, is inhibited significantly by dominant-negative RacN17. Equal inhibition is achieved by blocking PAK interaction with the guanine nucleotide exchange factor PIX using a specific N-terminal PAK fragment. We conclude that PAK, via its N-terminal non-catalytic domain, acts upstream of Rac mediating lamellipodia formation through interaction with PIX.

Animals↗

Temporal dynamics of verbal object comprehension.

Knowledge of the stage composition and the temporal dynamics of human cognitive operations is critical for building theories of higher mental activity. This information has been difficult to acquire, even with different combinations of techniques such as refined behavioral testing, electrical recording/interference, and metabolic imaging studies. Verbal object comprehension was studied herein in a single individual, by using three tasks (object naming, auditory word comprehension, and visual word comprehension), two languages (English and Farsi), and four techniques (stimulus manipulation, direct cortical electrical interference, electrocorticography, and a variation of the technique of direct cortical electrical interference to produce time-delimited effects, called timeslicing), in a subject in whom indwelling subdural electrode arrays had been placed for clinical purposes. Electrical interference at a pair of electrodes on the left lateral occipitotemporal gyrus interfered with naming in both languages and with comprehension in the language tested (English). The naming and comprehension deficit resulted from interference with processing of verbal object meaning. Electrocorticography indices of cortical activation at this site during naming started 250-300 msec after visual stimulus presentation. By using the timeslicing technique, which varies the onset of electrical interference relative to the behavioral task, we found that completion of processing for verbal object meaning varied from 450 to 750 msec after current onset. This variability was found to be a function of the subject's familiarity with the objects.

Adult↗

Evaluation of a modified APTT-based method for determination of APC resistance in plasma from patients on heparin or oral anticoagulant therapy.

An APTT-based kit method (Coatest APC Resistance), modified by predilution 1+4 of sample plasma in a plasma diluent containing a heparin antagonist (V-DEF plasma), has been evaluated on plasmas from patients treated with unfractionated (n = 110) or either of three different low molecular heparins (n=44), or with oral anticoagulants (n=147). Irrespective of treatment, no difference was observed in the APC response as compared to untreated individuals (n=62), and a complete discrimination was obtained between individuals with a normal factor V genotype and those carrying the FV:Q506 mutation. Furthermore, in contrast to the original, APTT-based kit method, where anticoagulant therapy results in a prolongation of the APTT, the modified kit provided APTT values within the normal range for orally anticoagulated (INR< or =6) and for all heparin treated (< or =1 IU/mL) patients except for one with a suspected presence of phospholipid antibodies. Due to the predilution in V-DEF plasma, contamination with platelets up to 1.5 x 10(4)/microL had a negligible effect on analysis of frozen plasmas regarding their classification as normal or abnormal. Analyses of fresh plasmas show no influence at platelet counts up to 6x10(4)/microL. Consequently, negligible differences in APC ratios were obtained between fresh and frozen plasmas. In conclusion, the modified kit method is applicable to plasmas from anticoagulated patients as well as from untreated individuals, allowing a safe assignment regarding the presence or absence of the FV:Q506 genotype.

Administration, Oral↗

In-situ hydration studies using multi-angle energy-dispersive diffraction.

A new diffractometer has been built with which energy-dispersive diffraction patterns can be collected simultaneously at different angles. The first use of this system for dynamic (time-resolved) studies--the hydration of cements under various conditions--is reported. It is found that the optimization available with a three-element detector system enables collection of high-quality patterns over a much wider and more effective range of reciprocal space, and this yields improved and new information on the hydration processes.

Journal Article↗

N-terminal proANF in acute atrial fibrillation: a biochemical marker of atrial pressures but not a predictor for conversion to sinus rhythm. Digitalis in Acute Atrial Fibrillation (DAAF) Trial group.

BACKGROUND: Atrial filling pressures are increased in acute atrial fibrillation, which stimulates the release of atrial natriuretic factor pro-hormone, proANF. METHODS: In a randomized trial comparing digoxin with placebo in 216 patients, we investigated whether the baseline plasma level of N-terminal proANF is a predictor for conversion to sinus rhythm and the relation among N-terminal proANF, conversion to sinus rhythm, and changes in heart rate. RESULTS: N-terminal proANF was increased at baseline and decreased significantly in patients converting to sinus rhythm, whereas it was mainly unchanged in nonconverters. N-terminal proANF was not a predictor of conversion to sinus rhythm. A relation was found between relative changes in heart rate and N-terminal proANF in nonconverters. CONCLUSION: The level of N-terminal proANF does not predict conversion to sinus rhythm, which indicates that hemodynamics per se is not important. There is a correlation between relative changes in heart rate and N-terminal proANF in nonconverters.

Acute Disease↗

Calphostin C induces selective disassembly of the Golgi complex by a protein kinase C-independent mechanism.

Intact cells incubated with calphostin C, an inhibitor of the regulatory domain of protein kinase C, showed fragmentation and dispersal of the Golgi complex by a light-dependent mechanism. At the ultrastructural level Golgi stacks were replaced by clusters of vesicles and short tubules that resembled the Golgi remnants present in control mitotic cells. Vesicle-mediated transport processes along both the exocytic and endocytic routes were also inhibited by calphostin C treatment. Golgi disassembly, however, was not due to protein kinase C inhibition since several inhibitors of the catalytic domain did not cause a similar effect. In contrast, pretreatment with phorbol 12-myristate 13-acetate partly protected the Golgi complex from disassembly by calphostin C. The in vitro effect was shown to be reversible, required both cytosol and ATP and it was inhibited by pretreatment of the Golgi membranes with trypsin but not with high salt. These results suggest the interaction of calphostin C with a structural Golgi protein containing a phorbol ester-binding domain and necessary for the stability of this organelle during interphase.

Adenosine Triphosphate↗

A histopathological assessment of the response of rectal adenocarcinoma to combination chemo-radiotherapy: relationship to apoptotic activity, p53 and bcl-2 expression.

AIMS: To investigate the use of pre-operative chemo-irradiation in downstaging advanced rectal cancer prior to surgical resection. METHODS: We examined the pathological effects of chemo-irradiation on 24 rectal tumours and correlated the efficacy of treatment with the level of apoptosis, mitosis, P53 and bcl-2 protein expression on pre-treatment biopsies. RESULTS: All tumours were resectable following chemo-irradiation. Six cancers showed complete regression with no viable tumour in the resection specimen. A significant correlation was found between spontaneous tumour apoptosis and tumour regression. CONCLUSIONS: Our results suggest that in rectal cancer the apoptotic rate in untreated tumour tissue may predict sensitivity to radiation and cytotoxic agents. No relationship was found between regression and mitotic rate, p53 or bcl-2 expression.

Adenocarcinoma↗

Screening for colorectal cancer: present, past and future.

Colorectal cancer results in 18,000 deaths annually in England and Wales, with 24,000 new cases diagnosed each year. Despite a better understanding of the genetics, and advancement in surgical and anaesthetic techniques, there has been little reduction in mortality and morbidity from this disease over the past 25 years. Colorectal cancer fits recognized criteria for a disease that should be screened in asymptomatic individuals. The putative duration of the adenoma to carcinoma sequence gives an ample window of opportunity to detect and treat colorectal cancer. In this article we have reviewed the strategies involved in screening for colorectal cancer in an asymptomatic population. We have presented trials and arguments for and against the different screening methods and discussed cost effectiveness of screening. In the USA and Canada, major professional organizations and societies now endorse screening; in the UK it is still far from being accepted. We feel that the available evidence shows that colorectal cancer screening has the potential to reduce the morbidity and mortality from this disease and that funding for a mass screening and public education programme should be sought.

Adenoma↗

Fibromyalgia and women's pursuit of personal goals: a daily process analysis.

For 30 days, 50 women with primary fibromyalgia syndrome reported daily progress and effort toward a health-fitness and a social-interpersonal goal and the extent to which their pain and fatigue hindered their accomplishment. They also carried palmtop computers to assess their sleep and their pain, fatigue, and positive and negative mood throughout the day. Analyses of the person-day data set showed that on days during which pain or fatigue increased from morning to evening, participants perceived their goal progress to be more attenuated by pain and fatigue. Unrestorative sleep the night before predicted the following day's effort and progress toward accomplishing health-fitness goals, but not social-interpersonal goals. Finally, participants who reported more progress toward social-interpersonal goals on a given day were more likely to evidence improvements in positive mood across the day, regardless of any changes in pain or fatigue that day.

Adaptation, Psychological↗

HIV-infected subjects with the E4 allele for APOE have excess dementia and peripheral neuropathy.

HIV produces a chronic viral infection of the central nervous system that elicits chronic glial activation and overexpression of glial cytokines that are also implicated in Alzheimer disease (AD) pathogenesis. A genetic risk factor for AD is the E4 isoform for apolipoprotein E (APOE). Here we compare the frequency of neurologic symptoms for subjects with and without the E4 isoform (E4(+)and E4(-), respectively) in an HIV cohort. Compared with E4(-) subjects, twice as many E4(+) subjects were demented (30% compared with 15%) or had peripheral neuropathy (70% compared with 39%) at least once, and they had threefold more symptomatic examinations (13% compared with 3% and 42% compared with 14%, respectively)(P < 0.0001). Thus, neurologic symptoms for HIV-infection and AD are linked through an etiologic risk factor. Long-term survivors of HIV infection with E4 may be at high risk for AD; conversely, gene-viral interactions may speed AD pathogenesis.

AIDS Dementia Complex↗

An experimental study of cardiac natriuretic peptides as markers of development of congestive heart failure.

The use of cardiac peptide measurements as possible diagnostic tools in congestive heart failure has been extensively discussed in the recent literature. Therefore, the aim of this study was to establish a model of experimental chronic heart failure, and thereby perform a comparative study of secretion and circulating levels of the cardiac peptides atrial natriuretic peptide (ANP), N-terminal proatrial natriuretic peptide (N-terminal proANP) and brain natriuretic peptide (BNP) during evolving heart failure. Chronic heart failure was induced in seven pigs by rapid left atrial pacing for three weeks. The effects of failure induction were documented 24 h after pacemaker deactivation. Hemodynamic indices of cardiac preload, like pulmonary capillary wedge pressure (PCWP) and right atrial pressure (RAP), were all considerably increased compared to sham operated controls. Likewise, plasma endothelin-L, noradrenaline, renin activity, aldosterone and angiotensin II were all markedly increased. Heart failure was accompanied by significant increases in both estimated cardiac secretory rate and plasma concentrations of all three cardiac peptides, significantly correlated to the PCWP. The directional changes during evolving heart failure were similar, although the percentage increase in plasma BNP was much larger than for ANP and N-terminal proANP. In absolute molar terms, however, the BNP concentration changes were minor compared to those of the other two peptides. The larger percentage increase of BNP might indicate its superiority as a marker of heart failure development, provided a functional assay suitable for clinical use can be designed for a peptide circulating in this low concentration range.

Aldosterone↗

Power of plasma N-terminal proatrial natriuretic factor to determine haemodynamics in patients with cardiac disease: relation to serum creatinine.

OBJECTIVE: The aim was to examine the usefulness of plasma N-terminal proatrial natriuretic factor (N-terminal proANP) as a non-invasive marker of cardiac pressure in patients with normal to mildly elevated serum creatinine. METHODS: Blood samples were drawn at rest from 100 patients with cardiac disease undergoing diagnostic cardiac catheterization. RESULTS: Using multivariate analysis, N-terminal proANP was independently related to mean pulmonary capillary wedge pressure (PCWP), mean right atrial pressure, serum creatinine (s-creatinine) and cardiac index. These indices accounted for about 50% of the variation in N-terminal proANP. All patients with N-terminal proANP < 1000 pmol/l had normal PCWP (< 13 mmHg). Areas under the receiver-operating characteristic (ROC) curves for N-terminal proANP for the detection of PCWP > or = 13, > or = 18 and > or = 24 mmHg were 0.903, 0.870 and 0.876, respectively. CONCLUSION: These results suggest that analysis of plasma N-terminal proANP is a simple and powerful method for assessing cardiac pressure in patients with heart disease and normal and mildly elevated s-creatinine (< 165 micromol/l). The value of N-terminal proANP cannot, however, indiscriminately be used to assess cardiac haemodynamics. N-terminal proANP measurement is a useful screening parameter for identifying patients with normal cardiac pressures.

Adolescent↗

Deletions in HOXD13 segregate with an identical, novel foot malformation in two unrelated families.

Synpolydactyly (SPD) is a dominantly inherited congenital limb malformation consisting of 3/4 syndactyly in the hands and 4/5 syndactyly in the feet, with digit duplication in the syndactylous web. The condition recently has been found to result from different-sized expansions of an amino-terminal polyalanine tract in HOXD13. We report a novel type of mutation in HOXD13, associated in some cases with features of classic SPD and in all cases with a novel foot phenotype. In two unrelated families, each with a different intragenic deletion in HOXD13, all mutation carriers have a rudimentary extra digit between the first and second metatarsals and often between the fourth and fifth metatarsals as well. This phenotype has not been reported in any mice with genetic modifications of the HoxD gene cluster. The two different deletions affect the first exon and the homeobox, respectively, in each case producing frameshifts followed by a long stretch of novel sequence and a premature stop codon. Although the affected genes may encode proteins that exert a dominant negative or novel effect, they are most likely to act as null alleles. Either possibility has interesting implications for the role of HOXD13 in human autopod development.

Chromosome Segregation↗

Adverse neonatal effects of maternal labetalol treatment.

Two infants with features of severe beta adrenergic blockade, pericardial effusions, and myocardial hypertrophy were born to mothers receiving long term treatment with oral labetalol for hypertension in pregnancy. Labetalol was implicated in the aetiology of these problems. Pericardial effusion and myocardial hypertrophy have not been associated with labetalol toxicity in neonates.

Adrenergic beta-Agonists↗

CSF, plasma viral load and HIV associated dementia.

Plasma viral burden has proven valuable in predicting the future course of systemic HIV related disease and the response to treatment. It is not known whether plasma or cerebrospinal fluid (CSF) viral burden can be used to predict onset of or response to treatment of nervous system disease. We propose a model of viral load mediated neurotoxicity underlying peripheral and central HIV associated neurological disease. The objective of this preliminary study was to assess the relationship of HIV associated neurological disease to quantitative viral load in plasma and CSF. 47 subjects (HIV- = 10, HIV+ = 37) participated in the study. Plasma and CSF samples were collected within a 3 h window. RT-PCR (Roche Amplicor Monitor) was utilized to assess HIV-1 RNA viral load in both plasma and cell free (centrifuged) CSF. Subjects underwent concurrent comprehensive neurological and neuropsychological evaluations. In general, systemic viral load, as measured in plasma, was greater than that found in cell free CSF. Cell free CSF HIV RNA viral load was significantly correlated with neurological dysfunction, whereas plasma viral load was not. The sole subject with an elevated CSF viral load (> 5 Log 10), had HIV associated dementia (HAD) on clinical examination.

AIDS Dementia Complex↗