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Biomedical subjects

S Jones

Publications and source records attributed to S Jones.

At least 217 records · Page 12Linked to original sources
PubMed1999

Founder mutations in the LDL receptor gene contribute significantly to the familial hypercholesterolemia phenotype in the indigenous South African population of mixed ancestry.

The South African population harbors genes that are derived from varying degrees of admixture between indigenous groups and immigrants from Europe and the East. This study represents the first direct mutation-based attempt to determine the impact of admixture from other gene pools on the familial hypercholesterolemia (FH) phenotype in the recently founded Coloured population of South Africa, a people of mixed ancestry. A cohort of 236 apparently unrelated patients with clinical features of FH was screened for a common mutation causing familial defective apolipoprotein B-100 (FDB) and seven low-density lipoprotein receptor (LDLR) gene defects known to be relatively common in South Africans with FH. Six founder-type 'South African mutations' were responsible for FH in approximately 20% of the study population, while only 1 patient tested positive for the familial defective apolipoprotein B-100 mutation R3500Q. The detection of multiple founder-type LDLR gene mutations originating from European, Indian and Jewish populations provides direct genetic evidence that Caucasoid admixture contributes significantly to the apparently high prevalence of FH in South African patients of mixed ancestry. This study contributes to our knowledge of the biological history of this unique population and illustrates the potential consequences of recent admixture in populations with different disease risks.

Founder Effect↗
PubMed1999

Block and modified gating of cardiac calcium channel currents by terodiline.

1. Terodiline, an anticholinergic/antispasmodic drug effective in the treatment of urinary incontinence, is presently restricted due to adverse side effects on cardiac function. To characterize its effects on cardiac L-type Ca2+-channel current carried by Ca2+ (ICa, L) and Ba2+ (IBa,L), concentrations ranging from 0.1 to 100 microM were applied to whole-cell-configured guinea-pig ventricular myocytes. 2. Although sub-micromolar concentrations of terodiline had no effect on ICa,L at 0 mV, 100 microM drug reduced its amplitude to ca. 10% of pre-drug control. The estimated IC50 (15.2 microM in K+-dialysed cells, 12.2 microM in Cs+-dialysed cells; 0.1 Hz pulsing rate) is eight times higher than reported for ICa,L in bladder smooth muscle myocytes. 3. Terodiline affected ICa,L in a use-dependent manner; block increased when the pulsing rate was increased from 0.1 to 2 - 3 Hz, and when holding potential was lowered from -43 mV. The drug accelerated the decay of ICa,L at 0 mV in a concentration-dependent manner, and slowed the recovery of channels from inactivation. 4. Terodiline reduced peak IBa,L more effectively than peak ICa,L, and markedly accelerated the rate of inactivation of the current. 5. The results are discussed in terms of mechanisms of Ca2+ channel block and relation to the therapeutic and cardiotoxic effects of the drug.

Animals↗
PubMed1999

Regional variations in grass pollen seasons in the UK, long-term trends and forecast models.

BACKGROUND: Three sites in the UK have daily records of pollen spanning several decades, giving the longest data sets worldwide. Previous research on London data revealed decreasing severity of grass pollen seasons. This is often taken as a model for the whole country but comparisons with Derby and Cardiff, in different regions of local climate and land-use, emphasize the need for regional studies. OBJECTIVE: The grass pollen seasons were analysed for three contrasting long-term sites to provide regional insight into the changing incidence of hay fever. METHODS: Pollen was monitored by volumetric instruments using standard techniques. Data have been taken from 1961 to 1993 to examine variation in grass pollen seasons in relation to land-use changes, cumulative temperatures and rainfall. Models were developed to predict total seasonal catches. RESULTS: At Cardiff the annual counts and severity increased in the 1960s, declined in the 1970s and rose again in the 1980s. At Derby and London the annual counts and severity declined but at different rates. Start dates have tended to become earlier at Cardiff and Derby, but later at London. Trends in annual counts and severity are similar to changes in grassland areas but they cannot be accounted for entirely by these. Weather in spring and early summer has tended to become warmer but there are no sustained patterns in June and July. No trends are apparent in the rainfall records for these months. The maximum explanation (r2 >/= 95%) in forecast models was obtained using 10-day aggregates of weather. CONCLUSION: The contrasting patterns both in the pollen records and land-use changes between the three sites emphasize the need for regional data. The predictive models achieved a high degree of explanation enabling pollen season severity to be forecast with high confidence shortly before the start date.

Humans↗
PubMed1999

The extended role of the nurse: the United Kingdom perspective.

There has been considerable discussion and debate in the United Kingdom regarding the role and function of the nurse. This article outlines the main tenets of the debate, namely the extended/expanded role and function, and gives a brief overview of the situation to date. Professional guidance from the United Kingdom Central Council for Nurses, Midwives and Health Visitors is explored and the implications this has for the nurse in the exercise of accountability. The legal implications of the nursing function in an expanded role capacity is discussed, in particular in relation to legal accountability, with reference to existing case law. Recommendations are made for the development of the expanded role.

Forecasting↗
PubMed1999

A prospective study of chronic subdural haematomas in elderly patients.

OBJECTIVE: to study clinical features and prognosis of older people with chronic subdural haematoma who present to an elderly medicine department rather than a neurosurgical unit. DESIGN: prospective descriptive study with immediate and 6-month follow-up. SUBJECTS: patients aged 75 and over with chronic subdural haematoma presenting to an elderly medicine service, selected on the basis of age alone. METHODS: information was taken from inpatient notes and computerized tomographs and, for 6-month follow-up, from outpatient clinics, inpatient notes or via the general practitioner. RESULTS: the most common presenting features were falls and progressive neurological deficit. 42% of patients were known to be confused before their chronic subdural haematoma. Only 37% of the patients were treated by neurosurgeons. The others were managed conservatively either because they were unfit for surgery or the haematoma was small. There was only one death related to surgery but 31% of patients died within 6 months of diagnosis. CONCLUSION: Elderly patients in neurosurgical series are a selected subgroup of older patients with subdural haematoma.

Aged↗
PubMed1999

Genetic interactions in yeast between Ypt GTPases and Arf guanine nucleotide exchangers.

Two families of GTPases, Arfs and Ypt/rabs, are key regulators of vesicular transport. While Arf proteins are implicated in vesicle budding from the donor compartment, Ypt/rab proteins are involved in the targeting of vesicles to the acceptor compartment. Recently, we have shown a role for Ypt31/32p in exit from the yeast trans-Golgi, suggesting a possible function for Ypt/rab proteins in vesicle budding as well. Here we report the identification of a new member of the Sec7-domain family, SYT1, as a high-copy suppressor of a ypt31/32 mutation. Several proteins that belong to the Sec7-domain family, including the yeast Gea1p, have recently been shown to stimulate nucleotide exchange by Arf GTPases. Nucleotide exchange by Arf GTPases, the switch from the GDP- to the GTP-bound form, is thought to be crucial for their function. Sec7p itself has an important role in the yeast secretory pathway. However, its mechanism of action is not yet understood. We show that all members of the Sec7-domain family exhibit distinct genetic interactions with the YPT genes. Biochemical assays demonstrate that, although the homology between the members of the Sec7-domain family is relatively low (20-35%) and limited to a small domain, they all can act as guanine nucleotide exchange factors (GEFs) for Arf proteins, but not for Ypt GTPases. The Sec7-domain of Sec7p is sufficient for this activity. Interestingly, the Sec7 domain activity is inhibited by brefeldin A (BFA), a fungal metabolite that inhibits some of the Arf-GEFs, indicating that this domain is a target for BFA. These results demonstrate that the ability to act as Arf-GEFs is a general property of all Sec7-domain proteins in yeast. The genetic interactions observed between Arf GEFs and Ypt GTPases suggest the existence of a Ypt-Arf GTPase cascade in the secretory pathway.

ADP-Ribosylation Factors↗
PubMed1999

Randomized trial of hydroxyethyl starch versus gelatine for trauma resuscitation.

BACKGROUND: Previous studies have demonstrated the rapid increase in systemic capillary permeability after blunt trauma and its association with poor outcome. There are theoretical advantages in resuscitation with colloid fluids, which are well retained in the vascular compartment during times of capillary leak. The aim of this study was to compare the effects of posttrauma resuscitation with hydroxyethyl starch (HES) (molecular mass, 250 kDa) or gelatine (molecular mass, 30 kDa), the hypothesis being that HES would reduce capillary leak. METHODS: Forty-five patients suffering blunt trauma were randomized on admission to receive either gelatine (Gelofusine) (n = 21) or HES (Pentaspan) (n = 24) for the first 24 hours, after which the choice of fluid was at the discretion of the clinician. The mean Injury Severity Score for the HES and gelatine groups were 20.0 (range, 9-41) and 18.1 (range, 9-32), respectively (p = 0.43). Capillary permeability was assessed by urine albumin excretion rate for the first 24 hours. For 5 days the daily mean P(O2)/F(IO2) ratio, serum C-reactive protein, hemoglobin, white cell and platelet counts, prothrombin, and activated partial thromboplastin time were recorded. RESULTS: Capillary permeability was lower in HES-treated patients during the first 24 hours. Log mean (95% confidence interval) albumin excretion rate for gelatine and HES groups at 6 hours were 117.5 (84.9) and 46.8 (24.3) microg/min (p = 0.011), at 12 hours were 54.9 (30.0) and 17.2 (7.6) microg/min (p = 0.001), and at 24 hours were 50.5 (23.4) and 23.6 (16.3) microg/min (p = 0.030), respectively. The mean (95% confidence interval) P(O2)/F(IO2) ratio for the HES and gelatine groups 48 hours after admission were 324 (44) and 267 (43) mm Hg, respectively (p = 0.03). The mean (95% confidence interval) serum C-reactive protein in the HES and gelatine groups 24 hours after admission were 72.4 (19.2) and 105.7 (30.1) mg/L, respectively (p = 0.03). There were no significant differences in any of the hematologic parameters during the first 48 hours. CONCLUSION: The results suggest that compared with gelatine, resuscitation with HES reduces posttrauma capillary leak.

Adolescent↗
PubMed1999

The appearance of escape variants in vivo does not account for the failure of recombinant envelope vaccines to protect against simian immunodeficiency virus.

The presence or evolution of immune escape variants has been proposed to account for the failure of recombinant envelope vaccines to protect macaques against challenge with simian immunodeficiency virus (SIVmac). To address this issue, two groups of three cynomolgus macaques were immunized with recombinant SIV Env vaccines using two different vaccine schedules. One group of macaques received four injections of recombinant SIV gp120 in SAF-1 containing threonyl muramyl dipeptide as adjuvant. A second group were primed twice with recombinant vaccinia virus expressing SIV gp160 and then boosted twice with recombinant SIV gp120. Both vaccine schedules elicited neutralizing antibodies to Env. However, on the day of challenge, titres of anti-Env antibodies measured by ELISA were higher in macaques primed with recombinant vaccinia virus. Following intravenous challenge with 10 monkey infectious doses of the SIVmac J5M challenge stock, five of the six immunized macaques and all four naive controls became infected. The virus burdens in PBMC of macaques that were primed with recombinant vaccinia virus were lower than those of naive controls, as determined by virus titration and quantitative DNA PCR. Sequence analysis was performed on SIV env amplified from the blood of immunized and naive infected macaques. No variation of SIV env sequence was observed, even in macaques with a reduced virus load, suggesting that the appearance of immune escape variants does not account for the incomplete protection observed. In addition, this study indicates that the measurement of serum neutralizing antibodies may not provide a useful correlate for protection elicited by recombinant envelope vaccines.

Amino Acid Sequence↗
PubMed1999

Hypokalaemic paralysis revealing Sjögren syndrome in an elderly man.

A 73 year old white man presented with life threatening hypokalaemic paralysis requiring admission to an intensive care unit. Biochemical investigations showed severe hypokalaemia with hyperchloraemic metabolic acidosis, a spot urine pH of 6.5, and a positive urinary anion gap, establishing the diagnosis of distal renal tubular acidosis. Autoimmune tests revealed Sjögren syndrome as the underlying cause of the distal renal tubular acidosis. Full recovery followed potassium and alkali replacement. This dramatic presentation of Sjögren syndrome has not previously been reported in an elderly man.

Acidosis, Renal Tubular↗
PubMed1999

Ischemic preconditioning prevents postischemic P-selectin expression in the rat small intestine.

Ischemic preconditioning (IPC) prevents the deleterious effects of prolonged ischemia and reperfusion (I/R). Because leukocyte infiltration is required to produce the microvascular dysfunction induced by I/R in the small intestine, and P-selectin-dependent leukocyte rolling is a requisite step in this process, we hypothesized that IPC would attenuate postischemic P-selectin expression. To address this postulate, P-selectin expression was evaluated in nonischemic (control) rat jejunum and in rat jejunum subjected to I/R alone (20 min ischemia/60 min reperfusion), or IPC (5 min ischemia/10 min reperfusion) + I/R using a dual radiolabeled monoclonal antibody approach. I/R was associated with a sevenfold increase in jejunal P-selectin expression, an effect that was completely abolished by IPC. Exposing the bowel to adenosine deaminase or an adenosine A1, but not an A2, receptor antagonist during the period of preconditioning ischemia or to selective PKC antagonists during prolonged ischemia prevented the beneficial effect of IPC to limit I/R-induced P-selectin expression. Our data indicate that P-selectin expression is a novel downstream effector target of the adenosine-initiated, PKC-dependent, anti-inflammatory signaling pathway in IPC.

Adenosine↗
PubMed1999

Multicenter, phase II trial of exemestane as third-line hormonal therapy of postmenopausal women with metastatic breast cancer. Aromasin Study Group.

PURPOSE: To assess the antitumor activity, safety, and hormone-suppressive effects of the irreversible aromatase inactivator, exemestane (Aromasin, Pharmacia & Upjohn, Kalamazoo, MI), administered as third-line hormone therapy to postmenopausal women with metastatic breast cancer that is refractory to tamoxifen and megestrol acetate. PATIENTS AND METHODS: Exemestane was administered at a dose of 25 mg/d orally until patients experienced disease progression. The efficacy and safety of exemestane were clinically and radiographically evaluated. The impact of exemestane treatment on tumor-related signs and symptoms was assessed. The effect of exemestane on serum levels of estrogens and other steroidal hormones was determined. RESULTS: Ninety-one patients were treated. There were four complete responses (CR) and eight partial responses (PR), for an objective response rate of 13% in the entire treated population. The overall success rate (CR, PR, or stable disease [SD] >/= 24 weeks) was 30%. The median duration of response and overall success was 9 months and 8 months, respectively. Most patients with CR/PR (83%; 10 of 12 patients) and SD >/= 24 weeks (80%; 12 of 15 patients) had improved or stable tumor-related signs and symptoms. Mean levels of circulating estrone (E(1)), estradiol (E(2)), and estrone sulfate decreased to 11%, 22%, and 13% of baseline levels, respectively (at week 8 or 16 of treatment). One half of the patients had undetectable E(1) and E(2) levels during treatment, including at the time of disease progression. Mild nausea (20% of patients) and hot flashes (20%) were the most common drug-related adverse events and were generally grade 1. CONCLUSION: Exemestane is an active and well-tolerated third-line hormonal therapy that represents a new treatment option for postmenopausal patients with advanced breast cancer that has become refractory to standard first- and second-line hormonal therapies.

Adult↗
PubMed1999

Self-reported psychopathy: a validation study.

Two studies are reported examining the reliability and validity of Levenson's Self-Report Psychopathy Scale (LSRP; Levenson, Kiehl, & Fitzpatrick, 1995) in a noninstitutionalized population. The first study used 1,958 undergraduates to examine the factor structure of the LSRP and its relation to serious antisocial behavior and common dimensions of personality. The second study (n = 70) included performance tasks known to discriminate psychopathic from nonpsychopathic prisoners. Results of the studies support the reliability and validity of the LSRP. The 2-factor structure of the inventory was strongly replicated in a series of confirmatory factor analyses. Predicted relations were observed between the LSRP and other self-report instruments of delinquency. In addition, the factors of the LSRP demonstrated the predicted divergent relations to traditional personality traits. Finally, psychopathic undergraduates showed deficits in response modulation similar to those observed in incarcerated psychopaths. Implications for psychopathy in general are also discussed.

Adult↗
PubMed1999

A Wnt5a pathway underlies outgrowth of multiple structures in the vertebrate embryo.

Morphogenesis depends on the precise control of basic cellular processes such as cell proliferation and differentiation. Wnt5a may regulate these processes since it is expressed in a gradient at the caudal end of the growing embryo during gastrulation, and later in the distal-most aspect of several structures that extend from the body. A loss-of-function mutation of Wnt5a leads to an inability to extend the A-P axis due to a progressive reduction in the size of caudal structures. In the limbs, truncation of the proximal skeleton and absence of distal digits correlates with reduced proliferation of putative progenitor cells within the progress zone. However, expression of progress zone markers, and several genes implicated in distal outgrowth and patterning including Distalless, Hoxd and Fgf family members was not altered. Taken together with the outgrowth defects observed in the developing face, ears and genitals, our data indicates that Wnt5a regulates a pathway common to many structures whose development requires extension from the primary body axis. The reduced number of proliferating cells in both the progress zone and the primitive streak mesoderm suggests that one function of Wnt5a is to regulate the proliferation of progenitor cells.

Abnormalities, Multiple↗
PubMed1999

Rickettsia serosurvey in Kimberley, Western Australia.

To determine if antibodies to rickettsiae (scrub typhus, spotted fever, and typhus group rickettsiae) occur among persons living in the Kimberley (northern tropical) region of Western Australia, 920 sera collected in a non-random manner in 1996 from patients in Kununurra, Broome, Fitzroy Crossing, Wyndham, Derby, and Halls Creek were tested by micro-immunofluorescence for antibodies to a panel of rickettsial antigens. Of 920 sera examined, 52 (5.6%) were positive for antibodies to one or more of the three groups of rickettsial microorganisms. The largest group of sera (24; 2.6%) were positive for scrub typhus (Orientia tsutsugamushi). Eleven other sera (1.2%) were positive for scrub typhus and spotted fever group rickettsiae and four (0.4%) were positive for scrub typhus, spotted fever group, and typhus group rickettsiae. In addition 13 sera (1.4%) were positive only for spotted fever group rickettsiae. In this study, only titers > or = 1:256 were considered significant. Thus, there is serologic evidence for scrub typhus and spotted fever group rickettsial infections in the Kimberley region of Western Australia. Because of the method of serum collection, it is not possible to determine the prevalence of seropositivity, but the data support the need for a proper epidemiologic study of rickettsial diseases in this region of Australia.

Antibodies, Bacterial↗
PubMed1999

The on-eye dehydration of proclear compatibles lenses.

PURPOSE: The purpose of the study was to evaluate the on-eye dehydration over time, of molded omafilcon A lenses (Proclear Compatibles) compared to a range of frequent replacement lenses. METHODS: Ten subjects wore a Proclear Compatibles lens in one eye and a control lens in the other eye for 4-, 8- and 12-hours. The control lenses were Acuvue, Soflens 66 and Optima frequent replacement lenses. Each subject wore three different pairs of lenses for each time period in a masked, randomized fashion. A gravimetric technique was used to determine lens water content. RESULTS: The Proclear Compatibles lenses showed significantly less relative dehydration than the Acuvue and Soflens 66 lenses. The Acuvue and Soflens 66 lenses showed a significant increase in relative dehydration with increasing wearing time. Subjective comfort was graded higher with the Proclear Compatibles than with the Acuvue lenses. There was a significant negative correlation between Acuvue dehydration and subjective ratings of comfort. CONCLUSIONS: The study showed that Proclear Compatibles lenses dehydrate significantly less than the other frequent replacement high-water content lenses. The Acuvue and Soflens 66 lenses showed increasing dehydration during the 4-12 hour wearing period.

Contact Lenses, Hydrophilic↗