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Biomedical subjects

J Meadows

Publications and source records attributed to J Meadows.

At least 19 recordsLinked to original sources

Asymptomatic Chiari Type I malformations identified on magnetic resonance imaging.

OBJECT: Chiari Type I malformation (CMI) is a congenital disorder recognized by caudal displacement of the cerebellar tonsils through the foramen magnum and into the cervical canal. Frequently, associated findings include abnormalities of nearby bony and neural elements as well as syringomyelia. Cerebellar tonsillar ectopia is generally considered pathological when greater than 5 mm below the foramen magnum. However, asymptomatic tonsillar ectopia is an increasingly recognized phenomenon, the significance of which is poorly understood. METHODS: The authors retrospectively reviewed the records of all brain magnetic resonance (MR) images obtained at our hospital over a 43-month period in an attempt to ascertain the relative prevalence and MR imaging characteristics of asymptomatic CMIs. Of 22,591 patients who underwent MR imaging of the head and cervical spine, 175 were found to have CMIs with tonsillar herniation extending more than 5 mm below the foramen magnum. Of these, 25 (14%) were found to be clinically asymptomatic. The average extent of ectopia in this population was 11.4 +/- 4.86 mm, and was significantly associated with a smaller cisterna magna. Syringomyelia and osseous anomalies were found in only one asymptomatic patient. CONCLUSIONS: The authors suggest that the isolated finding of tonsillar herniation is of limited prognostic utility and must be considered in the context of all available clinical and radiographic data. Strategies for treating patients with asymptomatic CMIs are discussed.

Adult↗

The physical association and phosphorylation of Cdc25C protein phosphatase by Prk.

prk encodes a protein serine/threonine kinase involved in regulating M phase functions during the cell cycle. We have expressed His6-Prk and His6-Cdc25C proteins using the baculoviral vector expression system. Purified recombinant His6-Prk, but not a kinase-defective mutant His6-PrkK52R, is capable of strongly phosphorylating His6-Cdc25C in vitro. Co-immunoprecipitation and affinity column chromatography experiments demonstrate that GST-Prk and native Cdc25C interact. When co-infected with His6-Prk and His6-Cdc25C recombinant baculoviruses, sf-9 cells produce His6-Cdc25C antigen with an additional slower mobility band on denaturing polyacrylamide gels compared with cells infected with His6-Cdc25C baculovirus alone. In addition, His6-Cdc25C immunoprecipitated from sf-9 cells co-infected with His6-Prk and His6-Cdc25C baculoviruses, but not with His6-PrkK52R and His6-Cdc25C baculoviruses, contains a greatly enhanced kinase activity that phosphorylates His6-Cdc25C in vitro. Moreover, phosphopeptide mapping shows that His6-Prk phosphorylates His6-Cdc25C at two sites in vitro and that the major phosphorylation site co-migrates with the one that is phosphorylated in vivo in asynchonized cells. Further studies reveal that His6-Prk phosphorylates Cdc25C on serine216, a residue also phosphorylated by Chk1 and Chk2. Together, these observations strongly suggest that Prk's role in mitosis is at least partly mediated through direct regulation of Cdc25C.

Animals↗

BUBR1 phosphorylation is regulated during mitotic checkpoint activation.

Eukaryotic cells have evolved a mechanism that delays the progression of mitosis until condensed chromosomes are properly positioned on the mitotic spindle. To understand the molecular basis of such monitoring mechanism in human cells, we have been studying genes that regulate the mitotic checkpoint. Our early studies have led to the cloning of a full-length cDNA encoding MAD3-like protein (also termed BUBR1/MAD3/SSK1). Dot blot analyses show that BUBR1 mRNA is expressed in tissues with a high mitotic index but not in differentiated tissues. Western blot analyses show that in asynchronous cells, BUBR1 protein primarily exhibits a molecular mass of 120 kDa, and its expression is detected in most cell lines examined. In addition, BUBR1 is present during various stages of the cell cycle. As cells enter later S and G2, BUBR1 levels are increased significantly. Nocodazole-arrested mitotic cells obtained by mechanical shake-off contain BUBR1 antigen with a slower mobility on denaturing SDS gels. Phosphatase treatment restores the slowly migrating band to the interphase state, indicating that the slow mobility of the BUBR1 antigen is attributable to phosphorylation. Furthermore, purified recombinant His6-BUBR1 is capable of autophosphorylation. Our studies indicate that BUBR1 phosphorylation status is regulated during spindle disruption. Considering its strong homology to BUB1 protein kinase, BUBR1 may also play an important role in mitotic checkpoint control by phosphorylation of a critical cellular component(s) of the mitotic checkpoint pathway.

Cell Cycle Proteins↗

Mental health problems in older adults with HIV referred to a psychological medicine unit.

Although HIV is still seen by many as a disease affecting younger adults, it is known that at least 11% of individuals with AIDS in Britain are over the age of 50. It is likely that this older age representation will continue and increase and whilst much is known about the psychological wellbeing of younger individuals with HIV, it is crucial that we consider the differing experiences and needs of older adults with the disease. Fifty-two adults with HIV over the age of 54 were referred to the Department of Psychological Medicine between June 1990 and December 1996. Data for these patients were compared with corresponding information for a random sample of younger patients with HIV. The older adults were found to differ significantly from the younger individuals on a variety of social, psychological and medical variables including social isolation, employment worries, sexuality, previous psychiatric history and stage of HIV at referral. It seems that current HIV services may actually alienate a significant proportion of potential users through not being sensitive to the needs and views of these older individuals. This must be addressed by policy makers and practitioners to ensure that psychiatric and psychological services become more acceptable and accessible to the older adult.

Adult↗

Human Bub1: a putative spindle checkpoint kinase closely linked to cell proliferation.

Eukaryotic cells have evolved a mechanism that delays the onset of anaphase until chromosomes are properly positioned on the spindle. To understand the molecular basis of such surveillance mechanism in human cells, we have cloned a full-length cDNA encoding a putative mitotic checkpoint kinase termed hBub1. Sequence comparison reveals that hBub1 is a structurally conserved protein, sharing 23% amino acid residue identity with BUB1 of budding yeast. In addition, the NH2-terminal portion (161 amino acids) of hBub1 shows a significant homology to yeast MAD3, a protein also known to be involved in the mitotic checkpoint response pathway. Northern blot analyses show that the hBub1 mRNA level is abundantly expressed in tissues or cells with a high mitotic index. When Dami cells undergo terminal differentiation after treatment with phorbol ester, hBub1 expression in this cell line is down-regulated rapidly. The hBub1 protein level is low in G1 and remains relatively constant in S, G2, and M phases. Immunofluorescence analysis shows that hBub1 protein colocalizes with a centromere-kinetochore antigen CREST in interphase, mitotic prophase, and nocodazole-treated cells. Antibody electroporation experiments show that hBub1 is an important component of the spindle checkpoint pathway. Furthermore, fluorescence in situ hybridization analysis maps the hBub1 gene to chromosome 2q12-13. Our studies suggest that hBub1 expression is restricted to proliferating cells and appears to be involved in regulating cell cycle progression. The molecular cloning of hBub1 cDNA will facilitate the study of its role in spindle checkpoint control as well as its potential role in certain genetic disorders.

Amino Acid Sequence↗

Are reported stress and coping style associated with frequent recurrence of genital herpes?

OBJECTIVES: This paper reports on the cross sectional data from the longitudinal study examining the impact of genital herpes simplex virus (HSV) infection on quality of life. In particular the report sought to study the relation between recurrence of genital HSV and coping style, mood, personality, and quality of life, among other factors. SETTING AND SUBJECTS: 116 patients with a known history of genital herpes simplex infection attending the Department of Genitourinary Medicine at Chelsea and Westminster Hospital. METHODS: Psychosocial factors (stress, anxiety, depression, health locus of control, personality, social support, coping skills, and quality of life) and the reported frequency of genital herpes episodes were measured using self administered questionnaires designed to examine the relation between psychosocial status and the frequency of genital HSV episodes. RESULTS: The number of recurrences reported by patients was significantly related to the style of coping skills used. Higher recurrences were less likely to use problem focused coping skills of planning and active coping, and the emotion focused coping skills of positive reinterpretation and growth. There was a significant difference in the number of patients who believed that psychological stress was related to the number of recurrences they experienced. This belief was related to neuroticism on the Eysenck Personality Questionnaire scale, and not to any of the other measures investigated. CONCLUSION: The findings suggest that it is the way individuals cope, and their personality characteristics rather than actual levels of psychological stress, that influence their belief in a link between recurrent genital HSV and stress. HSV may become the focus of existing concerns and be viewed as the physical manifestation of stress.

Adaptation, Psychological↗

Women and HIV infection: investigation of its psychosocial consequences.

HIV infection is associated with substantial psychological and social morbidity, although there is a dearth of studies of women with the infection. In recent years, developed countries have reported an increase in the prevalence of HIV infection in women, a fact that makes it all the more important to address the study of their psychological and social status. The study is a controlled investigation of HIV seropositive (n = 49) and seronegative women (n = 43), including study of psychological status and history, social functioning and perceived supports, coping style, life events, and sexual difficulties. The results show that about a third of women were psychiatric cases, regardless of HIV status, although more than half of symptomatic women were psychiatric cases. Seropositive women were less likely to use instrumental social supports and more likely to use mental disengagement as ways of coping. Regarding perceived social supports, positive women had lower scores on social integration and guidance. Positive women were more likely to experience sexual difficulties and not to be in a relationship. Negative women reported more adverse life events in the last 6 months. Psychiatric morbidity was associated with poorer social adjustment and more adverse life events, but not with serostatus. HIV positive women and those at risk of HIV infection have substantial levels of psychological and social morbidity that require recognition by those involved in their care and provision of adequate mental health intervention.

Adaptation, Psychological↗

Testing patients for HIV before surgery: the views of doctors performing surgery.

The aim of this study was to investigate the attitudes of doctors performing surgery to the HIV antibody testing of surgical patients. Fifty of eighty (62.5%) doctors performing surgery who are working in two London teaching hospitals returned completed anonymous postal questionnaires. Sixty-six per cent of the sample would like some form of compulsory testing of pre-operative patients, although most of them feel that this is only necessary for patients considered to be in 'high-risk groups'. Eighty-four per cent believe that this would ensure their safety from infection during surgery. Forty-eight per cent agreed with testing patients without their consent. Results suggest that most of the doctors performing surgery in this study agree with compulsory HIV antibody testing of pre-operative patients in the belief that this would protect them from infection during surgery. The problems associated with compulsory testing and relying on such testing in order to protect doctors from infection during surgery are discussed.

AIDS Serodiagnosis↗

Who chooses to have the HIV antibody test in the antenatal clinic?

With the increase in human immunodeficiency virus (HIV) seroprevalence amongst antenatal clinic attenders, and given that current medical opinion considers it desirable that a woman is aware of her serostatus, it has been recommended that the HIV test is offered to all women in the antenatal clinic and that its uptake is monitored. This paper reports on the uptake rate during the 12 months to February 1990 at a central London hospital, which was 17%, and the characteristics of the women who agreed to be tested for HIV. Using information collected by the midwife on an interactive computer during the 'booking' interview, it was found that women who were single and not in a stable relationship (p < 0.001) and those who described themselves as Mediterranean (p < 0.01) were more likely to accept the test. Caucasian women (p < 0.05) and married women (p < 0.05) were less likely to accept the test. Accepters did not differ from decliners in any other variable examined. Possible reasons for these differences are discussed.

AIDS Serodiagnosis↗

HIV antibody testing in the antenatal clinic.

With the increase in human immunodeficiency virus (HIV) seroprevalence amongst women attending the antenatal clinic in the UK it is essential that women are adequately prepared to make an informed decision about being tested for HIV and to receive the result of such testing. This paper discusses the purpose of testing, the necessity of pre-test counselling, its content and the practical implications of providing it. Guidelines for the content of a pre-test counselling session are outlined with particular reference to issues pertinent to the pregnant woman: vertical transmission, the effect of pregnancy on disease progression, the effect of HIV on pregnancy, the prognosis for an infected child and so on.

AIDS Serodiagnosis↗

HIV antibody testing in the antenatal clinic: the views of the consumers.

OBJECTIVE: to investigate the attitudes of parturient women to HIV antibody testing in the antenatal clinic. DESIGN; anonymous self completion questionnaire. SUBJECTS: 318 women attending antenatal clinic for their first booking appointment. SETTINGS: a central London hospital, UK. RESULTS: 58% of the women felt that testing should not be compulsory, 33% that it should. Sixty per cent felt that results of the test should be given as routine but 38% felt that they should only be given if requested. Fifty five per cent felt the HIV test was as important as all the other routine tests and 60% felt that they personally did not need to be tested. Only 44% wanted to speak to a midwife about the test, with 23% saying that they did not want to speak to anyone at all. The main reason given for accepting testing was concern about passing the virus on to the baby, which was also the main concern if the test was found positive. Few women (23%) felt that those identified as positive should be encouraged to terminate their pregnancy. CONCLUSIONS: policy decisions around HIV testing should take into account the diversity of the needs and wants of this multicultural and multiracial group of consumers.

AIDS Serodiagnosis↗

"I plan to have the HIV test"--predictors of testing intention in women attending a London antenatal clinic.

In order to identify which factors predict a parturient womans intention to take up voluntary HIV testing in the antenatal clinic, 318 women were surveyed by anonymous self-completion questionnaire. The strongest predictors of intention to be tested were the perceived benefit of the test to the woman herself, her partner, and the midwife, perceived risk of HIV infection, younger age and being single and having a poor knowledge of the sexual routes of HIV transmission. Health education strategies should therefore concentrate on: (a) increasing the parturient woman's knowledge of HIV transmission which will increase accuracy of perception of risk; and (b) stressing the potential benefits of HIV testing to all antenatal attenders, particularly to those who are older and in long term relationships.

AIDS Serodiagnosis↗

Testing for HIV in the antenatal clinic: the views of midwives.

Self administered questionnaires were given to 34 midwives, who regularly counsel parturient women about the HIV antibody test, to investigate their attitudes to the test being offered in the antenatal clinic. Most of the midwives felt that testing should not be compulsory and that the test should be offered to all pregnant women who ask for it, not only those in recognized risk groups. Most also felt that women should be told the results of the test and that it should not be the midwives aim to increase the number of women having the test. Most felt that all midwives should counsel about the test but would like health advisers, GPs and obstetricians to be involved also. They also felt that they did not have sufficient knowledge in some areas to counsel particularly with regard to the practical and psychological implications of being HIV positive. This has implications in terms of the provision of adequate pre-test counselling for all pregnant women as an improvement in counselling services requires an allocation of finances, e.g. for training of midwives, which may be seen as unnecessary in areas of low seroprevalence. Further discussion and debate of these issues is required.

AIDS Serodiagnosis↗