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M James

Publications and source records attributed to M James.

At least 37 records · Page 2Linked to original sources
PubMed2000

Active ERK/MAP kinase is targeted to newly forming cell-matrix adhesions by integrin engagement and v-Src.

Integrin engagement generates cellular signals leading to the recruitment of structural and signalling molecules which, in concert with rearrangements of the actin cytoskeleton, leads to the formation of focal adhesion complexes. Using antisera reactive either with total ERK or with phosphorylated/activated forms of ERK, in rat embryo fibroblasts and embryonic avian cells that express v-Src, we found that active ERK is targeted to newly forming focal adhesions after integrin engagement or activation of v-Src. UO126, an inhibitor of MAP kinase kinase 1 (MEK1), suppressed focal adhesion targeting of active ERK and cell spreading. Also, integrin engagement and v-Src induced myosin light chain kinase (MLCK)-dependent phosphorylation of myosin light chain downstream of the MEK/ERK pathway, and MLCK and myosin activities are required for the focal adhesion targeting of ERK. The translocation of active ERK to newly forming focal adhesions may direct specificity towards appropriate downstream targets that influence adhesion assembly. These findings support a role for ERK in the regulation of the adhesion/cytoskeletal network and provide an explanation for the role of ERK in cell motility.

Animals↗
PubMed2000

Co-localisation of CCG repeats and chromosome deletion breakpoints in Jacobsen syndrome: evidence for a common mechanism of chromosome breakage.

Folate-sensitive fragile sites are associated with the expansion and hypermethylation of CCG-repeats. The fragile site in 11q23.3, FRA11B, has been shown to cause chromosome deletions in vivo, its expression being associated with Jacobsen (11q-) syndrome. However, the majority of Jacobsen deletions are distal to FRA11B and are not related to its expression. To test the hypothesis that other unidentified fragile sites might be located in 11q23.3-24 and may cause these deletions, we have identified and characterised CCG-trinucleotide repeats within a 40 Mb YAC contig spanning distal chromosome 11q. Only eight CCG-repeats were identified within the entire YAC contig (not including FRA11B ), six of which map to the region of 11q23.3-24 that includes Jacobsen deletions. We have previously collated the deletion mapping data of 24 Jacobsen patients with the physical map of chromosome 11q, and accurately localised six breakpoints to short intervals corresponding to individual YAC clones. We now show that in each of these cases, YAC clones found to contain a deletion breakpoint also contain a CCG-repeat. The improved analysis of one of these deletions, together with those of several new Jacobsen cases, further strengthens this association by localising five breakpoints to individual PAC clones containing CCG-repeats. These data provide strong evidence for the non-random clustering of chromosome deletion breakpoints with CCG-repeats, and suggests that they may play an important role in a common mechanism of chromosome breakage.

Abnormalities, Multiple↗
PubMed2000

Evolutionary conservation of redundancy between a diverged pair of forkhead transcription factor homologues.

The Caenorhabditis elegans gene pes-1 encodes a transcription factor of the forkhead family and is expressed in specific cells of the early embryo. Despite these observations suggesting pes-1 to have an important regulatory role in embryogenesis, inactivation of pes-1 caused no apparent phenotype. This lack of phenotype is a consequence of genetic redundancy. Whereas a weak, transitory effect was observed upon disruption of just T14G12.4 (renamed fkh-2) gene function, simultaneous disruption of the activity of both fkh-2 and pes-1 resulted in a penetrant lethal phenotype. Sequence comparison suggests these two forkhead genes are not closely related and the functional association of fkh-2 and pes-1 was only explored because of the similarity of their expression patterns. Conservation of the fkh-2/pes-1 genetic redundancy between C. elegans and the related species C. briggsae was demonstrated. Interestingly the redundancy in C. briggsae is not as complete as in C. elegans and this could be explained by alterations of pes-1 specific to the C. briggsae ancestry. With overlapping function retained on an evolutionary time-scale, genetic redundancy may be extensive and expression pattern data could, as here, have a crucial role in characterization of developmental processes.

Amino Acid Sequence↗
PubMed2000

Adhesion-dependent tyrosine phosphorylation of (beta)-dystroglycan regulates its interaction with utrophin.

Many cell adhesion-dependent processes are regulated by tyrosine phosphorylation. In order to investigate the role of tyrosine phosphorylation of the utrophin-dystroglycan complex we treated suspended or adherent cultures of HeLa cells with peroxyvanadate and immunoprecipitated (beta)-dystroglycan and utrophin from cell extracts. Western blotting of (&bgr;)-dystroglycan and utrophin revealed adhesion- and peroxyvanadate-dependent mobility shifts which were recognised by anti-phospho-tyrosine antibodies. Using maltose binding protein fusion constructs to the carboxy-terminal domains of utrophin we were able to demonstrate specific interactions between the WW, EF and ZZ domains of utrophin and (beta)-dystroglycan by co-immunoprecipitation with endogenous (beta)-dystroglycan. In extracts from cells treated with peroxyvanadate, where endogenous (beta)-dystroglycan was tyrosine phosphorylated, (beta)-dystroglycan was no longer co-immunoprecipitated with utrophin fusion constructs. Peptide 'SPOTs' assays confirmed that tyrosine phosphorylation of (beta)-dystroglycan regulated the binding of utrophin. The phosphorylated tyrosine was identified as Y(892) in the (beta)-dystroglycan WW domain binding motif PPxY thus demonstrating the physiological regulation of the (beta)-dystroglycan/utrophin interaction by adhesion-dependent tyrosine phosphorylation.

Amino Acid Motifs↗
PubMed2000

Chronic relapsing pancreatitis in a child. Use of the Puestow procedure to achieve ductal drainage.

A case of chronic relapsing pancreatitis presenting in an 8-year-old African Jamaican girl is outlined. Aggressive supportive management failed to control pain and vomiting. The Puestow Procedure effectively procedure aborted these symptoms. The use of the Puestow procedure should not be inordinately delayed in chronic relapsing pancreatitis if symptoms persist, since it may not only control pain but also halt declining pancreatic function.

Child↗
PubMed2000

Ten years of liver transplantation at Groote Schuur Hospital.

INTRODUCTION: Liver transplantation has evolved from an experimental procedure to being the treatment of choice for many patients with end-stage liver disease, and is performed on a routine basis in most major centres throughout the world. However, certain situations peculiar to developing countries have a major impact on liver transplant programmes in these countries. We present the results of the liver transplant programme in Cape Town. PATIENTS AND METHODS: All patients undergoing orthotopic liver transplantation at Groote Schuur Hospital and Red Cross War Memorial Children's Hospital were included in this report. Standard surgical techniques were used for procuring the donor liver, the recipient hepatectomy and the subsequent implantation of the liver. All patients received standardised peri-operative management; in particular, the immunosuppressive protocol consisted of cyclosporin, steroids and azathioprine. Since October 1988, 83 patients have undergone 89 orthotopic liver transplants. There were 44 adults and 39 children, the age range being from 6 months to 56 years. The commonest indications for hepatic transplantation in adults included cryptogenic cirrhosis, auto-immune hepatitis and primary sclerosing cholangitis. In children biliary atresia was the commonest cause of liver failure. RESULTS: Of the 81 patients transplanted, 50 are alive and well with follow-up ranging from 2 months to 9.5 years. The cumulative graft survival rate was 72% at 1 year and 61% at 5 years. Six patients have undergone re-transplantation and 4 patients have had combined liver/kidney transplants. De novo hepatitis due to hepatitis B virus (HBV) has occurred in 8 patients following transplantation. Subsequent investigation has shown that 5 of the donors of these livers were hepatitis B core antibody (HBcAb)-positive, while information on the remaining 3 was not available. Tuberculosis (TB) has been a significant problem in 4 patients, with 2 deaths precipitated by anti-TB drug-induced hepatitis. Post-transplant lymphoproliferative disorder was also responsible for significant postoperative morbidity. CONCLUSION: Orthotopic liver transplantation has been established at Groote Schuur Hospital as the treatment of choice for selected patients with chronic end-stage liver disease. However, hepatitis B and TB appear to present a problem. The particularly high prevalence of HBV carrier status in our donor population may necessitate the use of living donors in the future.

Adolescent↗
PubMed1999

Why do preterm infants die in the 1990s?

OBJECTIVES: To describe the mortality rate for preterm infants (born 23-36 completed weeks' gestational age) and to determine the causes of death, focusing on avoidable causes. DESIGN AND SETTING: Prospective cohort study of preterm infants born at Royal Women's Hospital, Melbourne (a tertiary referral hospital with a neonatal intensive care unit and a special care nursery) from January 1994 to December 1996. SUBJECTS: 2475 consecutive liveborn infants with gestational ages from 23 to 36 weeks. MAIN OUTCOME MEASURES: Mortality rate during the primary hospitalisation, and causes of death. RESULTS: The total mortality rate was 4.8% (118/2475). The mortality rate declined with increasing maturity. The decrease in mortality was rapid between 23 and 28 weeks' gestational age, from 64.5% at 23 weeks to 4.0% at 28 weeks, then slower, falling to 0.4% at 36 weeks. Fifty of the 118 infants who died had lethal congenital anomalies. Lethal anomalies accounted for three-quarters of deaths in infants aged 28-36 weeks. The mortality rate in infants free of lethal anomalies was 2.8% (68/2425) and only 0.2% (4/1759) for infants aged 32-36 weeks. In the 68 infants without lethal anomalies who died, few obvious preventable causes were identified. CONCLUSIONS: Mortality rates fell rapidly between 23 and 28 weeks' gestational age. Survival rates for preterm infants born after 31 weeks' gestational age approached the survival rates of term infants. Lethal congenital anomalies were the most common cause of death; preventable causes of death were rare.

Australia↗
PubMed1999

Role of ambulatory urodynamic monitoring in clinical urological practice.

A retrospective review was conducted of 125 ambulatory monitoring (AM) studies performed on 111 women and 11 men between 1992 and 1996. All patients had had conventional cystometry prior to AM. All tests were interpreted with the aid of event markers and urinary diaries. Ambulatory traces were reported using the definitions derived from Coolsaet's work. To assess the role of AM in routine clinical urological practice, ambulatory diagnoses were compared with those of conventional cystometry. A survey of patient management was carried out by postal questionnaire or review of hospital notes to determine whether AM had influenced patient management. The study showed that 53 of 94 (56.3%) patients with symptoms suggestive of detrusor overactivity had detrusor instability diagnosed on AM. Of those with symptoms suggestive of stress incontinence, 5 (29%) had genuine stress incontinence and 5 (29%) had detrusor instability. The remainder (42%) had normal tests. Overall in 79 of 125 tests (63.2%), additional urodynamic findings were made that correlated with symptoms. Following the survey of patient management, AM was shown to influence management in all but 8.7% patients. In summary, AM was felt to have been shown to be a useful additional tool in clinical urological practice for those patients where conventional cystometry had failed to explain their symptoms.

Adolescent↗
PubMed1999

The structures of picornaviral proteinases.

Picornaviruses are a family of positive-strand RNA viruses the members of which include poliovirus, hepatitis A virus, rhinovirus, foot-and-mouth disease virus and encephalomyocarditis virus. The genetic information contained in the single-stranded, positive sense RNA genome is expressed as a single protein of around 2000 amino acids. This primary product of protein synthesis, designated the polyprotein, is subsequently cleaved into the mature viral proteins by proteinases present within it. The properties of the three defined proteolytic activities present in the picornaviruses are reviewed and the three-dimensional structures of the hepatitis A 3C proteinase and the leader proteinase of foot-and-mouth disease virus as well as a model of the structure of the HRV2 2A proteinase are compared with those of chymotrypsin, papain and streptomyces griseus A proteinase, respectively.

3C Viral Proteases↗
PubMed1999

Towards an integrated needs and outcome framework.

The British National Health Service alongside many other western countries is faced with competing pressures for limited health care resources which reflect, along with an increased accountability of both purchasers and providers of health care, the need for a clear function of explicit prioritisation from those who purchase health care. To enable limited health resources to be thus allocated, purchasers of health care must, therefore, be able to quantify not only the needs of their populations, but to predict and measure the outcomes from a health care intervention. This paper is concerned with the value framework underlying the twin dimension of needs and outcome assessment and seeks to address this framework from the sociological, philosophical and economic perspective and to determine the implications for the underlying distributive ethic.

Efficiency, Organizational↗
PubMed1999

QTc dispersion and complex ventricular arrhythmias in untreated newly presenting hypertensive patients.

Increased dispersion of ventricular repolarisation (increased QT dispersion) is believed to predispose to arrhythmias associated with sudden death in certain cardiac diseases. Hypertension is also associated with increased risk of sudden death, particularly in those with left ventricular hypertrophy (LVH). Therefore, the first aim of this study is to look into the possible pathogenic role of QT dispersion on the ventricular arrhythmias occurring in a group of never-treated hypertensive patients. The second aim is to look at other possible determinants of QT dispersion (ie, level of blood pressure, hypokalaemia, electrocardiographic LVH and presence or absence of strain pattern) in hypertensive patients, and their relevance to complex ventricular arrhythmias. QTc (corrected QT) was measured in 70 newly presenting (never-treated) hypertensive patients (47 male, 23 female, mean age 51.9 +/- 12.5 years) from a standard 12-lead surface electrocardiogram (ECG). Blood pressure measurements and 24-h ECG holter recordings were performed in all patients. Serum potassium level was measured in 51 of the patients. Ventricular arrhythmias were classified using a modified Lown's scoring system. Maximum QTc, minimum QTc and QTc dispersion for all patients were 442 +/- 30.3 ms, 380 +/- 26.7 ms and 61.5 +/- 21.6 ms respectively. High grade ventricular arrhythmias (Lown's score >/=3) were found in 43% of the patients. The QTc dispersion was strongly correlated with the Lown's classification of arrhythmia and the age of the patients. Patients with more severe ectopy (Lown's score >/=3) were significantly older (57.4 +/- 10.3 years) compared to those with score </=2 (48.3 +/- 12.6 years) (P = 0.0067) and had a significantly greater QTc dispersion (69.9 +/- 22.5 ms vs55.2 +/- 18. 8 ms; P = 0.002). Presence of electrocardiographic strain did not affect the severity of arrhythmia, as 29% of the patients with LVH and strain had grade >/=3 Lown's score compared to 39% in the group with LVH but without strain. In the presence of relative hypokalaemia, hypertensive patients with LVH showed more QTc dispersion (85.7 +/- 15.5 ms) and a greater tendency for complex ventricular arrhythmias (100% grade >/=3 Lown's score) compared to those with LVH and normal serum potassium levels (64.1 +/- 22.6 ms and 35%, QTc dispersion and Lown's score >/=3, respectively P = 0. 05). The level of blood pressure had no effect on either the QTc dispersion or the prevalence of complex ventricular arrhythmias. Prevalence of complex ventricular arrhythmias in hypertensive patients is strongly correlated with QTc dispersion and age. When hypertensive patients with LVH have low potassium levels the risk of developing complex ventricular arrhythmias is significantly increased.

Aging↗
PubMed1999

Changing mortality and causes of death in infants 23-27 weeks' gestational age.

OBJECTIVE: To contrast the mortality rates and changes in the causes of death of very preterm infants (23-27 weeks), before and after the introduction of exogenous surfactant in 1991, and to identify any preventable causes of death remaining in the 1990s. METHODOLOGY: This was a cohort study on consecutive preterm infants of 23-27 weeks' gestational age born in the Royal Women's Hospital, Melbourne, a level III perinatal centre. The infants were livebirths free of lethal anomalies from two distinct eras, 1983-90, and 1992-96, inclusive. The main outcome measures were mortality during the primary hospitalization and the causes of death before and after the introduction of exogenous surfactant in 1991. RESULTS: In 1983-90, 261 of 508 livebirths (51.4%) of 23-27 weeks' gestational age died, a significantly higher proportion than the 109 of 384 (28.4%) livebirths who died in the period 1992-96. The mortality rate fell significantly with increasing gestational age and was lower at each week of gestational age in 1992-96. More infants who died in 1992-96 were treated intensively in the neonatal intensive care unit (NICU). Of the group of infants who died or who were treated intensively in NICU, respiratory causes of death predominated. However, the causes of death changed over time. In 1992-96 proportionally fewer infants died from respiratory causes (1983-90, 82.5%; 1992-96, 60.0%; odds ratio (OR) 0.31, 95%; confidence interval (CI) 0.16-0.57), but more from septic causes (1983-90, 14.3%; 1992-96, 43.8%; OR 4.9, 95%; CI 2.6-9.2). CONCLUSIONS: As the mortality rate has fallen over time, respiratory causes of death have diminished, but septic causes of death have increased. Further advances in the use of exogenous surfactant and respiratory support may reduce respiratory deaths. Effective strategies to reduce nosocomial infections are urgently required.

Cause of Death↗
PubMed1999

Pure stress leakage symptomatology: is it safe to discount detrusor instability?

OBJECTIVE: To determine whether the combination of a urological history and urinary diary, with rigorous selection criteria, can be used to define a group of women on whom urodynamic assessment is unnecessary prior to offering surgery for urinary stress incontinence. DESIGN: Retrospective review of the urodynamic records of women attending for assessment between January 1992 and December 1996. SETTING: Urodynamic Department, Southmead Hospital, Bristol. POPULATION: 5193 women who attended the urodynamic clinic during the five year study period. METHODS: Self-completion of a urinary diary in the preceding week before urodynamic assessment and a detailed urological history before undergoing cystometry by all women in the study period. Data were entered onto a computer database. Women reporting stress incontinence in the absence of bladder filling symptoms, with a normal urinary diary showing daytime frequency of seven times or less and nocturia of no more than once, had the results of their filling cystometry analysed. RESULTS: Of 5193 women, 555 had symptoms of pure stress incontinence and a normal urinary diary. Incontinence was confirmed objectively in 81%, with 9% having incontinence secondary to detrusor instability; 5% had detrusor instability as the sole cause of their incontinence with 4% having a mixed picture of detrusor instability incontinence and urethral sphincter weakness. CONCLUSION: Genuine stress incontinence cannot be diagnosed reliably from a urological history, even when rigorous selection criteria are used in combination with a normal urinary diary. Without cystometry, incontinence secondary to detrusor instability will be missed.

Female↗
PubMed1999

Two nursing home outbreaks of respiratory infection with Legionella sainthelensi.

OBJECTIVE: To describe outbreaks of infection caused by Legionella sainthelensi occurring in older residents of two nursing homes and to determine risk factors for the development of infection. DESIGN: Descriptive epidemiology and a case-control study. SETTING: Two nursing homes (140 beds and 254 beds in nursing homes A and B, respectively) located in southern Ontario, Canada, experiencing outbreaks of respiratory tract infection in July and August 1994. SUBJECTS: Case-residents of the two nursing homes who met clinical and laboratory criteria for Legionella infection. Control-residents were defined as those who were in the homes during the outbreaks and were asymptomatic. MEASUREMENTS: Active surveillance was conducted in both nursing homes to identify symptomatic residents. Residents with fever or respiratory tract symptoms had nasopharyngeal swabs taken for viral antigen detection and culture, urine for Legionella antigen detection, and acute and convalescent serology for viruses, Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella. Chest X-rays were performed, and an attempt was made to obtain blood and sputum cultures. Water samples from shower heads, faucets, and air conditioning units were collected for Legionella culture and polymerase chain reaction (PCR) assay. A case-control study was done to assess possible risk factors for legionellosis. RESULTS: Twenty-nine cases -- 17 in nursing home A; 12 in nursing home B - were identified. Four (14%) case-residents had documented pneumonia and four case-residents died. Univariate analysis revealed that a history of stroke (odds ratio (OR) 2.3 (95% CI, 1.0-5.3)), eating pureed food (OR 4.6 (95% CI, 1.6-12.7)), and having fluids administered with medication (OR 2.5 (95% CI, 1.0-5.9)) were significant risk factors. Cases were less likely to wear dentures (OR .4 (95% CI, .2-.9)) or to eat solid food (OR .3, (95% CI, .1-.6)). Only eating pureed food remained significant in a multivariable analysis (OR 4.6 (95% CI, 1.6-13.0, P = .01)). CONCLUSION: This report describes outbreaks of legionellosis in two nursing homes, representing the first reported outbreaks of infection caused by Legionella sainthelensi. The association with illness of dietary characteristics indicative of swallowing disorders suggests that aspiration was the most likely mode of infection. The diagnosis of legionellosis should be considered during outbreaks of respiratory infection in nursing homes.

Aged↗