Search PubMed⌕ Search

Biomedical subjects

C R Jones

Publications and source records attributed to C R Jones.

At least 19 recordsLinked to original sources
PubMed2007

Modeling of a human circadian mutation yields insights into clock regulation by PER2.

Circadian rhythms are endogenous oscillations of physiological and behavioral phenomena with period length of approximately 24 hr. A mutation in human Period 2 (hPER2), a gene crucial for resetting the central clock in response to light, is associated with familial advanced sleep phase syndrome (FASPS), an autosomal dominant condition with early morning awakening and early sleep times. The FASPS hPER2 S662G mutation resulted in PER2 being hypophosphorylated by casein kinase I (CKI) in vitro. We generated transgenic mice carrying the FASPS hPER2 S662G mutation and faithfully recapitulate the human phenotype. We show that phosphorylation at S662 leads to increased PER2 transcription and suggest that phosphorylation at another site leads to PER2 degradation. Altering CKIdelta dosage modulates the S662 phenotype demonstrating that CKIdelta can regulate period through PER2 in vivo. Modeling a naturally occurring human variant in mice has yielded novel insights into PER2 regulation.

Amino Acid Sequence↗
PubMed2003

Validation of the Welch Allyn 'Vital Signs' blood pressure measurement device in pregnancy and pre-eclampsia.

OBJECTIVE: To establish the accuracy the Welch Allyn 'Vital Signs' blood pressure monitor in pregnancy and pre-eclampsia according to a modified British Hypertension Society protocol. DESIGN: Prospective observational study. SETTING: Maternity Unit/Obstetric Ward, Guy's and St Thomas' Hospital, London, UK. POPULATION: Forty-three pregnant women of whom 12 had pre-eclampsia. METHODS: Nine sequential same-arm measurements were taken from each woman by two trained observers, alternating between a mercury sphygmomanometer and the device. The last seven readings were analysed according to the British Hypertension Society protocol. The accuracy of the device was determined using the grading scale indicated by the British Hypertension Society protocol (grade A/B = pass, grade C/D = fail). MAIN OUTCOME MEASURES: Grading criteria of the British Hypertension Society Protocol. RESULTS: The Welch Allyn 'Vital Signs' monitor achieved a grade A for both systolic and diastolic pressures in pregnant women who did not have pre-eclampsia. In those women with pre-eclampsia, it achieved a grade D and B for systolic and diastolic pressures, respectively. The mean differences between the observers and the device in women without pre-eclampsia were -2.6 (6.4) and -1.5 (7.2) mmHg for systolic and diastolic pressures [and in pre-eclamptic women -7.8 (6.3) and -5.5 (6.5)mmHg]. It therefore fulfils criteria set by the Association for the Advancement of Medical Instrumentation (mean <5 mmHg and standard deviation <8 mmHg) in pregnancy, but not in pre-eclampsia. CONCLUSION: This is the first automated device suitable for robust clinical use that can be recommended for use in pregnancy. However, it should be borne in mind that-similar to other devices--it significantly under--recorded readings obtained in pre-eclamptic women.

Blood Pressure↗
PubMed2001

An hPer2 phosphorylation site mutation in familial advanced sleep phase syndrome.

Familial advanced sleep phase syndrome (FASPS) is an autosomal dominant circadian rhythm variant; affected individuals are "morning larks" with a 4-hour advance of the sleep, temperature, and melatonin rhythms. Here we report localization of the FASPS gene near the telomere of chromosome 2q. A strong candidate gene (hPer2), a human homolog of the period gene in Drosophila, maps to the same locus. Affected individuals have a serine to glycine mutation within the casein kinase Iepsilon (CKIepsilon) binding region of hPER2, which causes hypophosphorylation by CKIepsilon in vitro. Thus, a variant in human sleep behavior can be attributed to a missense mutation in a clock component, hPER2, which alters the circadian period.

Amino Acid Sequence↗
PubMed2001

Validation of the Welch Allyn 'Vital Signs' oscillometric blood pressure monitor.

This study has determined the accuracy of the Welch Allyn 'Vital Signs' blood pressure (BP) monitoring device in an adult population, according to the criteria of the British Hypertension Society (British Hypertension Society, 1993). Validation was also classified by the American 'Association for the Advancement of Medical Instrumentation' (AAMI). The Welch Allyn 'Vital Signs' monitor achieved a BHS grade A for both systolic and diastolic BP. It also met the criteria for the AAMI protocol. The mean differences between trained observers using a mercury sphygmomanometer and the device were -1 +/- 5 mm Hg for systolic BP and -3 +/- 4 mm Hg for diastolic BP. The Welch Allyn 'Vital Signs' monitor can be recommended for clinical use in the adult population. This is one of the first oscillometric monitors designed for routine use in a hospital environment that has been found to provide an accurate assessment of BP by accepted validation procedures.

Adult↗
PubMed2001

A controlled study of cognitive deficits in children with chronic Lyme disease.

Although neurologic Lyme disease is known to cause cognitive dysfunction in adults, little is known about its long-term sequelae in children. Twenty children with a history of new-onset cognitive complaints after Lyme disease were compared with 20 matched healthy control subjects. Each child was assessed with measures of cognition and psychopathology. Children with Lyme disease had significantly more cognitive and psychiatric disturbances. Cognitive deficits were still found after controlling for anxiety, depression, and fatigue. Lyme disease in children may be accompanied by long-term neuropsychiatric disturbances, resulting in psychosocial and academic impairments. Areas for further study are discussed.

Adolescent↗
PubMed2000

Coexistent coronary and cerebrovascular disease: results of simultaneous surgical management in specific patient groups.

OBJECTIVE: Results of synchronous combined revascularization were examined in specific patient groups with coexistent coronary and cerebrovascular diseases. METHODS: Between 1.1.1980 and 31.12.1998, 408 patients underwent a synchronous combined carotid endarterectomy (CEA)+myocardial revascularization (CABG). In 259 (63.5%) patients, carotid disease was asymptomatic. Remaining patients presented with a previous stroke (n=35) or a transient ischemic episode (TIA) (n=114). In 245 (60%) patients, carotid stenosis was bilateral (Group A: bilateral > or =80% stenosis, Group B: contralateral occlusion, Group C: contralateral subcritical disease). A synchronous ipsilateral CEA+CABG was performed in all patients with an unilateral disease (n=163) and also in all Group B (n=33) and Group C (n=142) patients with bilateral disease. A simultaneous bilateral CEA+CABG was performed in 12 high risk Group A patients. Remaining Group A patients (n=58), initially underwent an ipsilateral CEA for most dominant lesion+CABG, soon followed by the contralateral CEA. Results were examined in above specific patient Groups. RESULTS: Overall combined hospital mortality from stroke+myocardial infarction was 2.45%. No independent predictor of stroke was identified. In general, initial prophylactic CEA, subdued the risk of subsequent strokes for 7-8yr. Predictors of a late stroke were: progression of bilateral (P=0.007) and intracranial (P=0.04) cerebrovascular disease. Highest risk of an early stroke was recorded in Group A patients. A composite high risk group of patients with multiple risk factors (n=155) demonstrated a higher risk of both early and late strokes, as compared to the remaining patients (n=253) (P<0.04). Observed risk of early and late strokes, in specific patient groups was lower than standard predictions. CONCLUSIONS: A regular use of combined approach was justified in the above patient groups.

Aged↗
PubMed2000

Iaterogenic injuries during retrograde delivery of cardioplegia.

During last eight years, retrograde delivery of cardioplegia was used on a regular basis, utilizing a DLP INC (Grand Rapids, MI) or a Research Medical INC (Salt Lake City UT) delivery systems, in almost an equal number of patients. This method resulted in a high pressure rupture, or perforation of the coronary sinus, its radicals or the right ventricle (RV) in 0.06% (5/7886) of patients. Intraoperative diagnosis of these injuries were confirmed on abnormal haemodynamic tracings and trans oesophageal echocardiography (TOE), and appearance of cardiac contusion or leakage of cardioplegia. A low incidence of these iaterogenic injuries may be attributed to: (1) a regular use of this method and (2) use of TOE guided manipulations in select high risk and reoperative patients. Repair of these injuries, as described, resulted in salvage of 4/5 (80%) patients.

Aged↗
PubMed2000

Evaluation and management of insomnia in menopause.

Insomnia is a problem with complex and multifactorial etiologies that requires both standardized and individualized treatment interventions. Specific targets of treatment may include hyperarousal, poor sleep habits, underlying mood disorders, sedative overuse, pain and general medical problems, circadian dysrhythmias, sleep apnea, and restless legs syndrome. Optimal treatment also will incorporate stress management, coping strategies, enhancement of relationships, and promoting lifestyle changes that facilitate sleep.

Complementary Therapies↗
PubMed2000

A validation of the Mobil O Graph (version 12) ambulatory blood pressure monitor.

OBJECTIVE: To assess the clinical accuracy of the Mobil O Graph (version 12) ambulatory blood pressure monitor in an adult population. METHODS: The accuracy of the device was assessed by predefined criteria (British Hypertension Society, BHS) in 85 subjects recruited from the patients and staff in a teaching hospital. A series of same-arm sequential blood pressure measurements were taken: first two observers taking simultaneous mercury readings, followed by a reading with the Mobil O Graph ambulatory monitor. A total of seven readings were taken from each subject in the sitting position. The data were then analysed according to the BHS protocol and the criteria of the Association for the Advancement of Medical Instrumentation (AAMI). RESULTS: The Mobil O Graph ambulatory monitor fulfilled the criteria of the BHS protocol, achieving a grade B for systolic blood pressure (SBP) and a grade A for diastolic blood pressure (DBP). The mean differences were -2+/-8 mmHg for SBP and -2+/-7 mmHg for DBP. The device therefore also passed the AAMI standard (the mean to be within 5+/-8 mmHg). CONCLUSION: The Mobil O Graph ambulatory monitor performed in a satisfactory manner according to the BHS and the AAMI criteria and can therefore be recommended for clinical use in the general population.

Adolescent↗
PubMed2000

High-affinity maltose binding and transport by the thermophilic anaerobe Thermoanaerobacter ethanolicus 39E.

Thermoanaerobacter ethanolicus is a gram-positive thermophile that produces considerable amounts of ethanol from soluble sugars and polymeric substrates, including starch. Growth on maltose, a product of starch hydrolysis, was associated with the production of a prominent membrane-associated protein that had an apparent molecular weight of 43,800 and was not detected in cells grown on xylose or glucose. Filter-binding assays revealed that cell membranes bound maltose with high affinity. Metabolic labeling of T. ethanolicus maltose-grown cells with [(14)C]palmitic acid showed that this protein was posttranslationally acylated. A maltose-binding protein was purified by using an amylose resin affinity column, and the binding constant was 270 nM. Since maltase activity was found only in the cytosol of fractionated cells and unlabeled glucose did not compete with radiolabeled maltose for uptake in whole cells, it appeared that maltose was transported intact. In whole-cell transport assays, the affinity for maltose was approximately 40 nM. Maltotriose and alpha-trehalose competitively inhibited maltose uptake in transport assays, whereas glucose, cellobiose, and a range of disaccharides had little effect. Based on these results, it appears that T. ethanolicus possesses a high-affinity, ABC type transport system that is specific for maltose, maltotriose, and alpha-trehalose.

Amino Acid Sequence↗
PubMed1999

Changes in excitability of motor cortical circuitry in primary restless legs syndrome.

OBJECTIVE: To investigate the excitability of segmental and suprasegmental systems in patients with primary restless legs syndrome (pRLS) by measuring the cortical silent period (C-SP) and the peripheral silent period (P-SP). BACKGROUND: There is some evidence that RLS may be the motor manifestation of normal CNS periodicity that becomes disinhibited under certain conditions. The mechanism of this disinhibition is unclear. DESIGN/METHODS: Ten patients with pRLS and 10 normal age-matched subjects were studied. The mixed nerve P-SP produced by electrical stimulation of the median and common peroneal nerves was recorded during maximal contraction of the abductor pollicis brevis (APB) and tibialis anterior (TA) muscles. The C-SP produced by a single magnetic shock to motor cortex at 150% of resting threshold was also measured during maximal contraction of the APB and TA muscles. The average of 5 to 10 trials at each site was obtained and compared using Student's t-test. RESULTS: Resting central motor threshold was not significantly different between pRLS patients and the control group. The average duration of the C-SP was shorter in the APB (74.5+/-37.7 versus 129.56+/-35.95 msec, p<0.05) and TA (66.81+/-25.63 versus 136.1+/-40.35 msec, p<0.05) in patients with pRLS. The P-SP duration, however, was not significantly different between two groups in either limb. CONCLUSION: The supraspinal inhibitory system is impaired in pRLS.

Adult↗
PubMed1999

Reinterventions for recurrent ischemic heart disease following a successful first re-do myocardial revascularization: predictors, indications and results.

Predictors for a reintervention following a successful first re-do surgical revascularization (CABG) were examined. Success and limitations of the reintervention procedures were evaluated. Between 3/88 and 3/95, 16.81% (302/1796) patients who had undergone a first re-do CABG surgery in the authors' center, required a reintervention. Graft angioplasty was performed in 158 (52.32%) patients and a second re-do CABG in 47.68% (n = 144). Graft angioplasty was preferred over surgery in patients aged 70 years or older (43% versus 24.3%, P<0.001) and in patients with unstable angina (55.6% versus 33.3%, NS) or a Left Ventricular Ejection Fraction (LVEF) <30% (34.8% versus 20%, P<0.05). Re-do CABG was preferred over graft angioplasty for multivessel revascularization (3+/-0.3 versus 1+/-0.6, P<0.001), proximal occlusive disease (P<0.001) and for graft disease of a longer duration (7.18+/-1.7 years versus 3+/-0.6 years, P<0.01). The independent predictors of a reintervention were (i) lack of arterial revascularization and (ii) inability to achieve a complete revascularization in a previous operation. The predictors of a failed graft angioplasty were diameter stenosis >70%, long occlusive lesions (multivariate), angulation, calcification and asymmetrical lesions (univariate). Failed graft angioplasty required a re-do CABG (n = 48: early 21, late 27), repeat graft angioplasty (n = 34: early 8, late 26) or transplant (n = 1). Recurrent symptoms following a second re-do CABG required a graft angioplasty (n = 6: early 2, late 4), a subsequent re-do CABG (n = 32) or a transplant (n = 4). Cumulative incidence of cardiac events at 1 month, and 1 and 8 years were: 20, 40.45 and 66.44% following graft angioplasty and 5.5, 10 and 56.55% following a second re-do CABG, respectively (P<0.05). Actuarial survival at 1 month and 6 years following graft angioplasty were 97.15 and 77.22%, and 94.7 and 83.26% after a second re-do CABG, respectively (NS). Re-do CABG was more effective and durable. Graft angioplasty provided a good palliation in suitable cases and also postponed the need for a high-risk surgical intervention for more favorable conditions.

Aged↗
PubMed1999

Familial advanced sleep-phase syndrome: A short-period circadian rhythm variant in humans.

Biological circadian clocks oscillate with an approximately 24-hour period, are ubiquitous, and presumably confer a selective advantage by anticipating the transitions between day and night. The circadian rhythms of sleep, melatonin secretion and body core temperature are thought to be generated by the suprachiasmatic nucleus of the hypothalamus, the anatomic locus of the mammalian circadian clock. Autosomal semi-dominant mutations in rodents with fast or slow biological clocks (that is, short or long endogenous period lengths; tau) are associated with phase-advanced or delayed sleep-wake rhythms, respectively. These models predict the existence of familial human circadian rhythm variants but none of the human circadian rhythm disorders are known to have a familial tendency. Although a slight 'morning lark' tendency is common, individuals with a large and disabling sleep phase-advance are rare. This disorder, advanced sleep-phase syndrome, is characterized by very early sleep onset and offset; only two cases are reported in young adults. Here we describe three kindreds with a profound phase advance of the sleep-wake, melatonin and temperature rhythms associated with a very short tau. The trait segregates as an autosomal dominant with high penetrance. These kindreds represent a well-characterized familial circadian rhythm variant in humans and provide a unique opportunity for genetic analysis of human circadian physiology.

Activity Cycles↗
PubMed1999

An investigation of the presence of ultramicrocells in natural mineral water.

The presence of 'ultramicrocells' in natural mineral water, capable of passing through a 0.2 micron filter, has been demonstrated. Filters allowing the greatest proportion of viable (culturable) cells to pass ranked in the order, 0.4 micron polycarbonate (5.02%) > 0.2 micron polycarbonate (0.02%) > or = 0.45 micron cellulose nitrate (0.02%) > 0.2 micron cellulose acetate (< 0.002%). Following incubation for 4 d at 22 degrees C, viable counts in filtered mineral water increased from < 2-8.7 x 10(2) cfu ml-1(-2).8 x 10(4)-1.9 x 10(6) cfu ml-1. Successive filtration/incubation cycles of mineral water increased the proportion of cells passing through a 0.2 micron cellulose acetate filter from < 0.003% to 0.11% and 0.69%, suggesting selection for 'ultramicrocells'. Cells isolated from this process and grown on liquid R2A medium were thin, Gram-negative rods, of 0.15-0.40 micron wide and 0.50-6.20 microns long. Membrane filtration techniques used for pathogen detection in mineral waters will not retain all the cells present. If pathogens are able to form ultramicrocells, these may go undetected.

Cellulose↗
PubMed1999

The role of surface physicochemical properties in determining the distribution of the autochthonous microflora in mineral water bottles.

Investigation of the distribution of the viable autochthonous microflora in three brands of 1-2-month-old bottled mineral water showed that 1.8 x 10(4) (S.E.M. 8.9 x 10(3), n = 5) to 1.2 x 10(5) (S.E.M. 1.3 x 10(4), n = 5) cfu ml-1 were planktonic cells while 11 (S.E.M. 4, n = 5)-632 (S.E.M. 176, n = 5) cfu cm-2 were found in the biofilm. The biofilm represented between 0.03 and 1.79% of the total viable microbial population in the 1.5 litre bottles studied. Scanning electron microscopy studies showed that the cells adhering to the polyethylene terephthalate (PET) bottles were predominantly rod-shaped, sparsely distributed over the surface. In contrast, the cells adhering to the high density polyethylene (HDPE) caps were found to be mainly clumps of coccoid cells, suggesting that the bottle may provide different microhabitats for different microfloras. Large-scale roughness, such as that observed as lettering inside the cap (average height (z) = 93 microns) was associated with a 46-fold increase in cell numbers. Increased small-scale roughness, as measured by atomic force microscopy on PET and HDPE surfaces (average roughness (Ra) = 5-551 (nm), showed no correlation with adhesion. Investigations of surface hydrophobicity by the sessile drop technique showed that contact angles (theta) were greater on the HDPE caps (theta = 89-96 degrees) than on the PET surfaces (theta = 69-80 degrees). However, no correlation was found between contact angle and attached cell numbers. Measurements of surface electrostatic charge by streaming potential showed that the PET carried an overall negative charge, measuring -15.9 to -16.6 mV in mineral water. No significant change in charge occurred when the monomer composition of the PET was altered. It was concluded that surface roughness, in particular the scale of surface topographical features, is the most important physicochemical surface characteristic determining the distribution of the autochthonous microflora in mineral water bottles.

Bacterial Adhesion↗
PubMed1998

Hemodynamic and coronary effects of the endothelin antagonist bosentan in patients with coronary artery disease.

BACKGROUND: Endothelin is a potent endothelium-derived vasoconstrictor peptide with proliferative properties. Elevated levels of the peptide occur in coronary artery disease; however, its pathophysiological role as a regulator of coronary tone and structure is uncertain. Endothelin-receptor antagonists are specific tools to clarify this issue and might be useful in the treatment of coronary artery disease. METHODS AND RESULTS: In a double-blind, placebo-controlled randomized study, we investigated the effects of the ETA/ETB endothelin-receptor antagonist bosentan or placebo on systemic and coronary hemodynamics in 28 patients with angiographically documented stable coronary artery disease by quantitative coronary angiography and an intracoronary Doppler guidewire. Bosentan 200 mg IV decreased systolic blood pressure (P<0. 05), whereas heart rate increased slightly (P<0.05). Coronary diameter increased, particularly in vessels with no or mild angiographic changes (P<0.01). Glycerol trinitrate did not further dilate these segments, whereas coronary diameter increased significantly after nitrate in the placebo group. The increase in coronary diameter after bosentan correlated inversely with plasma LDL-cholesterol levels (P<0.01) in both stenotic and angiographically normal coronary segments. Coronary flow velocity did not change. Bosentan was well tolerated. CONCLUSIONS: Endogenous endothelin exerts a vasoconstrictor tone in epicardial coronary arteries of patients with coronary artery disease, as evidenced by the vasodilation exerted by the combined ETA/ETB endothelin-receptor antagonist bosentan under acute conditions. Bosentan can safely be given to these patients. Hence, further long-term studies are necessary to determine the therapeutic potential of endothelin-receptor antagonists in patients with coronary artery disease.

Antihypertensive Agents↗