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G Black

Publications and source records attributed to G Black.

At least 19 recordsLinked to original sources
PubMed2006

Genotype-phenotype correlation in Costello syndrome: HRAS mutation analysis in 43 cases.

BACKGROUND: Costello syndrome (CS) is a rare multiple congenital abnormality syndrome, associated with failure to thrive and developmental delay. One of the more distinctive features in childhood is the development of facial warts, often nasolabial and in other moist body surfaces. Individuals with CS have an increased risk of malignancy, suggested to be about 17%. Recently, mutations in the HRAS gene on chromosome 11p13.3 have been found to cause CS. METHODS: We report here the results of HRAS analysis in 43 individuals with a clinical diagnosis of CS. RESULTS: Mutations were found in 37 (86%) of patients. Analysis of parental DNA samples was possible in 16 cases for both parents and in three cases for one parent, and confirmed the mutations as de novo in all of these cases. Three novel mutations (G12C, G12E, and K117R) were found in five cases. CONCLUSIONS: These results confirm that CS is caused, in most cases, by heterozygous missense mutations in the proto-oncogene HRAS. Analysis of the major phenotypic features by mutation suggests a potential correlation between malignancy risk and genotype, which is highest for patients with an uncommon (G12A) substitution. These results confirm that mutation testing for HRAS is a reliable diagnostic test for CS.

Abnormalities, Multiple↗
PubMed2002

Molecular genetic analysis of the NF2 gene in young patients with unilateral vestibular schwannomas.

Neurofibromatosis type 2 (NF2) must be suspected in patients presenting with a unilateral vestibular schwannoma at a young age who are therefore at theoretical risk of developing bilateral disease. We identified 45 patients aged 30 years or less at the onset of symptoms of a unilateral vestibular schwannoma. Molecular genetic analysis of the NF2 gene was completed on peripheral blood samples in all 45 and on 28 tumour samples. No pathogenic NF2 mutations were identified in any of the blood samples. NF2 point mutations were identified in 21/28 (75%) tumour samples and loss of heterozygosity (LOH) in 21/28 (75%) tumour samples. Both mutational hits were identified in 18/28 (65%) tumour samples. In one multilobular tumour, one (presumably first hit) mutation was confirmed which was common to different foci of the tumour, while the second mutational event differed between foci. The molecular findings in this patient were consistent with somatic mosaicism for NF2 and the clinical diagnosis was confirmed with the presence of two meningiomas on a follow up MRI scan. A further patient developed a contralateral vestibular schwannoma on a follow up MRI scan in whom neither of the truncating mutations in the vestibular schwannoma were present in blood. It is important when counselling patients with unilateral vestibular schwannomas to identify (1) those at risk of bilateral disease, (2) those at risk of developing other tumours, and (3) other family members at risk of developing NF2. Comparing tumour and blood DNA cannot exclude mosaicism in the index case and cannot, therefore, be used to predict those at risk of developing further tumours. However, identification of both mutations or one mutation plus LOH in the tumour and exclusion of those mutations in the blood samples of the sibs or offspring of the affected case may be sufficient to render further screening unnecessary in these relatives.

Adolescent↗
PubMed2001

The utility of panoramic imaging of the temporomandibular joint in patients with temporomandibular disorders.

OBJECTIVE: The objective of this study was to evaluate the utility of panoramic imaging in assessment of patients with temporomandibular disorders (TMDs). STUDY DESIGN: Fifty-five consecutive patients referred for diagnosis and management of facial pain and jaw dysfunction were included. A single examiner completed the history and clinical examination on all patients. All patients received panoramic imaging. On the basis of clinical and radiographic findings, a subset of patients received advanced imaging modalities. The panoramic radiographs were interpreted by 2 examiners; if any disagreement was noted, a third examiner interpreted the radiographs. RESULTS: Seventy-five percent of the patients had complaints of facial pain, and 75% exhibited tenderness in masticatory muscles. Tenderness was present in TM joint regions in 62%. Altered bony anatomy was seen in 43.6% of panoramic radiographs. Panoramic imaging did not lead to changes in clinical diagnosis in any of the patients seen, although the findings on the radiographs did lead to requests for additional imaging studies in 3 cases, one of which was later referred for surgical intervention because of radiographic findings. CONCLUSION: Clinical findings may be of greater relevance leading to the diagnoses associated with TMD and to determination of the need for additional imaging rather than the use of panoramic imaging in all patients with facial pain and TMD.

Adolescent↗
PubMed2001

Angelman syndrome phenotype associated with mutations in MECP2, a gene encoding a methyl CpG binding protein.

Angelman syndrome (AS) is a neurodevelopmental disorder characterised by severe mental retardation, absent speech, ataxia, sociable affect, and dysmorphic facial features. Eighty five percent of patients with AS have an identifiable genetic abnormality of chromosome 15q11-13. Mutations within the X linked MECP2 gene have been identified in patients with Rett syndrome (RTT), a neurodevelopmental disorder which affects females almost exclusively and which shares phenotypic overlap with AS. RTT is usually associated with normal development in infancy followed by loss of acquired skills and evolution of characteristic hand wringing movements and episodes of hyperventilation.A panel of 25 female and 22 male patients with a clinical diagnosis of AS and no molecular abnormality of 15q11-13 were screened for MECP2 mutations and these were identified in four females and one male. Following the diagnosis, it was possible to elicit a history of regression in three of these patients, who by then were showing features suggestive of Rett syndrome. In the remaining two subjects the clinical phenotype was still considered to be Angelman-like. These findings illustrate the phenotypic overlap between the two conditions and suggest that screening for MECP2 mutations should be considered in AS patients without a demonstrable molecular or cytogenetic abnormality of 15q11-13. Since MECP2 mutations almost always occur de novo, their identification will substantially affect genetic counselling for the families concerned.

Angelman Syndrome↗
PubMed2001

A survey of attitudes to abortion law in Northern Ireland amongst obstetricians, gynaecologists and family planning doctors.

CONTEXT: The Abortion Law in Northern Ireland - professional attitudes to change. OBJECTIVE: To elicit the attitudes of doctors in Northern Ireland, practicing obstetrics and gynaecology or family planning. METHOD: Questionnaires (n = 155) were sent to all grades of doctors working in obstetrics and gynaecology or family planning in Northern Ireland during 1996. RESULTS: One hundred and two (65.8%) of the questionnaires were returned. The majority of doctors believed that abortion should be legalised and a service provided. There was no consensus on how this should be achieved. Fifty percent of family planning doctors supported importing the British Abortion Law, but the majority of hospital doctors favoured a new law specific to Northern Ireland. Over 90% were in favour of providing medical abortions in certain circumstances. There was no agreement on who should be responsible for the service.

Abortion, Induced↗
PubMed2001

Comparison of two versus three smears in identifying culture-positive tuberculosis patients in a rural African setting with high HIV prevalence.

SETTING: Karonga district, northern Malawi. OBJECTIVE: To compare the sensitivity and specificity of two versus three smears for the diagnosis of pulmonary tuberculosis in a setting with high HIV prevalence. DESIGN: A total of 1992 pulmonary tuberculosis suspects with three sputum smears taken over a 2-7 day period and at least one culture result were studied. Smears were auramine stained and examined using fluorescence microscopy, and positives were confirmed with Ziehl-Neelsen staining and light microscopy. Cultures were set up on Löwenstein-Jensen media. True negative and positive status was defined on the basis of culture. The sensitivity, specificity, and positive and negative predictive values of two and three smears were compared. RESULTS: Compared to culture, the sensitivity, specificity, and positive and negative predictive values of three smears were 70%, 98%, 92%, and 92%, respectively. Restriction to the first two smears gave similar results. Of those detected as smear-positive using three smears, at least 97% would have been detected by two. Among those with HIV serology results available, the sensitivity of two smears for detecting culture-positive tuberculosis was identical to that using three. CONCLUSION: In this setting, using fluorescence and light microscopy, collecting two smears rather than three would only marginally reduce sensitivity and would slightly improve the specificity of diagnosis of tuberculosis; this is unaffected by HIV status. The potential for improving specificity is important because of the costs of misdiagnosis. In practice, both sensitivity and specificity may be increased due to the time saved by examining two rather than three smears.

AIDS-Related Opportunistic Infections↗
PubMed1999

Heterogeneity in granular corneal dystrophy: identification of three causative mutations in the TGFBI (BIGH3) gene-lessons for corneal amyloidogenesis.

Six autosomal dominant corneal dystrophies are caused by mutations in the TGFBI (BIGH3) gene on chromosome 5q31: three types of lattice corneal dystrophy (LCD), including type I and type IIIA, granular, Avellino (ACD), and Reis-Bucklers. Initially an exact genotype-phenotype correlation was reported. We report three families, with differing clinical features, all presenting with "granular" corneal dystrophy. We analysed the TGFBI gene by SSCP analysis and direct sequencing in order to further assess the genotype-phenotype correlation. We describe three separate mutations in TGFBI: one novel, one initially described as causing ACD, and one previously described. The novel mutation, R124S, is at the identical position to the mutation causing LCD type I (CDL1). We review the clinical and histological phenotypes of the corneal dystrophies and hypothesize that the ability of a mutation to cause amyloid deposition depends on the location and nature of the mutation. In addition, we suggest that the classification of the granular corneal dystrophies be revised according to mutation type and that ACD should not be classified as a distinct morphological entity.

Amyloid↗
PubMed1999

Probability of bilateral disease in people presenting with a unilateral vestibular schwannoma.

BACKGROUND: Some 4%-5% of those who develop vestibular schwannomas have neurofibromatosis type 2 (NF2). Although about 10% of these patients present initially with a unilateral vestibular schwannoma, the risk for a patient with a truly sporadic vestibular schwannoma developing contralateral disease is unknown. METHODS: A United Kingdom survey of 296 patients with NF2 was reviewed for laterality of vestibular schwannoma at presentation and the presence of other NF2 related features. The time to presentation of bilateral disease was calculated for patients presenting with a unilateral tumour. Mutation analysis of the NF2 gene was carried out on all available cases presenting initially with unilateral disease. RESULTS: Of 240 patients with NF2 with vestibular schwannomas, 45 (18%; 32 sporadic, 13 familial) had either a unilateral tumour or delay in detection between the first and contralateral tumours. Among those tested for NF2 mutations, eight of 27 and nine of 13 were identified among sporadic and familial cases respectively. Sporadic cases showed a high female to male ratio and 19 of 32 have not as yet developed a contralateral tumour (mean 4.1 years after diagnosis of the first). Thirteen of 32 sporadic patients developed a contralateral tumour (mean 6.5 years after the first tumour diagnosis, range 0-22 years) compared with 11 of 13 familial patients (mean delay 5 years, range 0-16 years). Seven of the 45 patients had neither a family history of NF2 nor evidence of related tumours at initial presentation (six before the age of 35 years). CONCLUSION: The risk of patients with sporadic unilateral vestibular schwannomata developing a contralateral tumour in the absence of family history or other features of NF2 is low, but those presenting with other neurogenic tumours in addition to vestibular schwannoma are at high risk of harbouring an NF2 mutation in at least a proportion of their somatic cells.

Adolescent↗
PubMed1998

Differential diagnosis of type 2 neurofibromatosis: molecular discrimination of NF2 and sporadic vestibular schwannomas.

Patients who present with unilateral vestibular schwannomas either at a young age or with additional features of type 2 neurofibromatosis (NF2) are at risk of developing bilateral disease and transmitting a risk of neurogenic tumours to their offspring. We have identified 15 patients from a series of 537 with unilateral vestibular schwannomas who also had one or more of the following: other tumours (10/15), features of NF2 (3/15), or a family history of neurogenic tumours (5/15). No germline NF2 mutations were detected and in 7/9 cases where tumour material was available for analysis a germline mutation in the NF2 gene has been excluded. Although a possibility of gonosomal mosaicism still exists, exclusion tests for the offspring are now possible. We suggest a general strategy, based on analysis of tumour DNA, for distinguishing sporadic and familial cases of tumours caused by two hit mechanisms. Application of this strategy suggests that most instances of unilateral vestibular schwannoma which do not fulfil criteria for NF2 represent chance occurrences.

Adult↗
PubMed1997

Cooperativeness and bully/victim problems among Australian schoolchildren.

The relationship was examined between the self-reported cooperativeness of Australian secondary-school students and their involvement in peer abuse at school, both as bullies and as victims. An 18-item Likert-type measure, the Cooperativeness Scale, was developed, and its reliability and concurrent validity were supported by the results of its application to two samples of Australian students (N = 176 and N = 763, respectively) attending different coeducational secondary schools, the first in a predominantly middle-class area and the second in a lower class socioeconomic area. At both schools, girls scored higher in cooperativeness than boys. Students at the second school also anonymously completed multiple measures of the extent of their involvement during the current year in bullying, victimization, or both. As predicted, correlations and multiple regression analyses supported the hypothesis that relatively low levels of cooperativeness were characteristic, not only of both boys and girls who engaged in bullying, but also, to a lesser extent, of those who were frequently victimized by their peers at school.

Adolescent↗
PubMed1997

Limited spatial clustering of individual Plasmodium falciparum alleles in field isolates from coastal Kenya.

We describe Plasmodium falciparum genetic diversity in coastal Kenya, typing S-antigen and the merozoite surface proteins 1 and 2 (MSP-1 and MSP-2) in field isolates by the polymerase chain reaction (PCR). Malaria in coastal Kenya is characterized by low seasonal transmission, and a relatively high incidence of severe disease, which tends to occur in time-space clusters. We chose the highly polymorphic S-antigen as a marker for localized parasite diversity because it has been shown to vary in serotype prevalence in time and space. A total of 261 children (up to nine years of age) in two neighboring locations with different transmission rates were sampled for blood-stage parasites in cross-sectional surveys before and after the main transmission period in 1991, and also in a concomitant one-year longitudinal survey tracing clinical infections. Six major sequence types of S-antigen were identified, which were subdivided into 70 alleles; however, only 50% of isolates were typeable. The S-antigen sequence types varied qualitatively between locations, over time, and between asymptomatic and clinical disease infections, but not between different age groups. The MSP-1 and MSP-2 sequence type prevalences, in contrast, did not differ in any of these comparisons. We describe the use of the Mantel test for assessing clustering of individual parasite alleles at the household level, and demonstrate low-level clustering of MSP-1 and MSP-2 alleles and S-antigen sequence types, at the end of a long period of low transmission.

Age Factors↗
PubMed1997

Receptor-specific adhesion and clinical disease in Plasmodium falciparum.

One important factor in the virulence of infections with Plasmodium falciparum is the adherence of infected erythrocytes to small vessel endothelium. In infections that lead to serious, life-threatening disease accumulation of large numbers of infected cells in particular organs is thought to lead to organ dysfunction or failure. This is of particular relevance when the affected organ is the brain, leading to the development of cerebral malaria. Many different endothelial receptors for infected red blood cells have been identified. Some receptors such as CD36 and thrombospondin are used by all parasite isolates, whereas others such as intercellular adhesion molecule-1 (ICAM-1) or vascular cell adhesion molecule (VCAM) are used by a subset of field and laboratory isolates. While it has been speculated that the ability to bind or affinity of binding to a particular endothelial receptor may be related to the pattern of disease, only studies with limited numbers of patients have been carried out to date and these have been in general inconclusive. Here we have taken parasite isolates from 150 patients with defined clinical syndromes as well as isolates from 50 healthy but parasitized community controls and quantitatively assessed their binding to purified endothelial receptors in vitro. Our results show that disregarding the level of adhesion, all parasites bind to CD36, most bind to ICAM-1, few bind to VCAM, and almost none bind to E-selectin. In assessing the degree of binding we show that 1) binding to all receptors was reduced in parasites taken from severely anemic patients; 2) binding to CD36 is identical in parasites from cerebral malaria patients and community controls but slightly elevated in parasites from nonsevere cases; and 3) binding to ICAM-1 is highest in cerebral malaria patients. Because rosette formation by uninfected cells has also been a phenotype associated with disease severity and one that may interfere in vitro with receptor binding, we also assessed rosette formation in all isolates. In this study the highest level of rosette-forming parasites was found in the anemic group and not the cerebral malaria group. Stratifying the data for the frequency of rosette formation showed that the above results were not significantly altered by this phenomenon. Our data are not consistent with a role for binding to CD36 in the development of severe disease but show an association between the degree of binding to ICAM-1 and clinical illness in nonanemic patients.

Anemia↗
PubMed1996

Cardiopulmonary bypass leads to a preferential loss of activated platelets. A flow cytometric assay of platelet surface antigens.

OBJECTIVE: In a prospective study surface antigens associated with platelet activation, aggregation, and adhesion and the platelet volume were measured to investigate the mechanism of the platelet function defect of cardiopulmonary bypass (CPB). METHODS: Blood samples were obtained during cardiac surgery before and after heparinization, as well as during and following extracorporeal circulation. The expression of the platelet surface glycoproteins (GP) IIb-IIIa, Ib, 53, and the granule membrane protein (GMP) 140 were measured using flow cytometry in platelet-rich plasma (PRP) before and after in vitro stimulation with adenosine diphosphate. A full blood count including mean platelet volume (MPV) was taken. RESULTS: Heparinization resulted in a significant increase of GP 53 and GMP 140 and a significant decrease of GP Ib expression. During and following CPB, GP IIb-IIIa and Ib were significantly decreased. Similarly, the expression of the activation markers was reduced significantly. The mean platelet volume decreased significantly from 8.6 +/- 0.7 fl at baseline to 7.9 +/- 0.8 fl at the end of the study period. CONCLUSION: Our data suggest that heparinization induces platelet activation. We assume that a loss of larger and more activated platelets from the circulation contributes substantially to the platelet function defect of CPB.

Adult↗
PubMed1996

Aprotinin has no effect on platelet activation and adhesion during cardiopulmonary bypass.

Aprotinin reduces blood loss following cardiopulmonary bypass operations (CPB) by the prevention of hyperfibrinolysis. Its influence on circulating platelets is uncertain. In this prospective trial we investigated activation, adhesion, and aggregation receptors on the platelet surface in 20 patients who underwent elective coronary artery bypass grafting. These patients were randomly assigned to receive either a high dose of aprotinin or placebo. Flow cytometry was performed to determine platelet activation [P-selectin, glycoprotein (GP) 53], adhesive (GP Ib), and aggregatory (GP IIb-IIIa) receptors on circulating platelets, before, during, and after CPB. Aprotinin had neither a significant effect on platelet activation nor on adhesive and aggregatory receptors. Plasma levels of D-dimers were measured before and after CPB to assess fibrinolytic activity. D-dimers following CPB and chest tube drainage were significantly less in the aprotinin group. We conclude that aprotinin reduces blood loss by its effect on fibrinolysis but has no direct influence on platelet function.

Adult↗
PubMed1995

Male neonatal death and progressive weakness and immune deficiency in females: an unknown X linked condition.

We report a family with an undiagnosed X linked condition. The grandmother, two of her three daughters, and one of her grand-daughters have a slowly progressive proximal weakness, brisk reflexes, poor bladder function, static reduced night vision, and IgG2 deficiency. The diagnosis of the three living symptomatic females was "hereditary spastic paraplegia plus". They have lost five male children who died in the neonatal period of severe hypotonia and were of low birth weight. Investigations have not led to a unifying diagnosis: myotonic dystrophy, NARP, and X linked hyper IgM were specifically eliminated. Using the hypothesis that the condition is X linked dominant, haplotype analysis of the family suggests that the disease locus is within Xq26-qter. This entity should be considered in the differential diagnosis of families presenting with severe neonatal hypotonia in males and females with symptoms suggestive of complex hereditary spastic paraplegia.

Adolescent↗
PubMed1994

The molecular biology of Norrie's disease.

The Norrie's disease gene has been accurately located on the short arm of the X chromosome. The methodology underlying this achievement and the structure of the three-exon gene is described in this review article. The clinical implications of these recent advances are discussed. Allelic variants of Norrie's disease and the phenomenon of females affected by X-linked disease are also discussed.

Chromosome Deletion↗
PubMed1993

Maternal and child health services in the Baltimore City Health Department, 1900-1992.

Maternal and Child Health Services in the Baltimore City Health Department, founded in 1934 and 1919, respectively, grew out of concern for maternal and infant death. Increasingly, services have focused on prevention and on building individual health by strengthening the family. The authors identify changing patterns of health care and the health department's continuing role in assuring high quality care and developing guidelines for cost-effective management.

Adult↗