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Biomedical subjects

J Read

Publications and source records attributed to J Read.

At least 37 records · Page 2Linked to original sources
PubMed1999

Baculovirus expression and biochemical characterization of the human microsomal triglyceride transfer protein.

The microsomal triglyceride transfer protein (MTP) complexed to protein disulphide isomerase (PDI) is obligatory for the assembly of chylomicrons and very-low-density lipoproteins. The determination of the atomic structure of the MTP-PDI heterodimer has important implications for the treatment of those forms of hyperlipidaemia associated with the overproduction of very-low-density lipoproteins, which predispose to premature coronary heart disease. To perform structural studies of the human MTP-PDI complex it was necessary to produce milligram quantities of pure protein. We chose the baculovirus expression system for this purpose. Insects cells were co-infected with recombinant viruses encoding FLAG-tagged MTP and His-tagged PDI; the resulting heterodimer was purified by affinity chromatography. From 5 litres of insect cells, 4-6 mg of more than 95% pure recombinant protein was obtained. CD and attenuated total reflection Fourier-transform infrared spectroscopy indicate that the purified protein has around 34% alpha-helical and 33% beta-structure content. The recombinant protein had a comparable triglyceride transfer activity to that of bovine MTP-PDI. The production of polyclonal antibodies raised against the MTP and PDI subunits of the purified protein is described. The present study demonstrates the feasibility of expressing two proteins at high levels in insect cells and describes a transferable methodology for the purification of the resulting protein complex.

Amino Acid Sequence↗
PubMed1999

The structure of vitellogenin provides a molecular model for the assembly and secretion of atherogenic lipoproteins.

The assembly of atherogenic lipoproteins requires the formation in the endoplasmic reticulum of a complex between apolipoprotein (apo)B, a microsomal triglyceride transfer protein (MTP) and protein disulphide isomerase (PDI). Here we show by molecular modelling and mutagenesis that the globular amino-terminal regions of apoB and MTP are closely related in structure to the ancient egg yolk storage protein, vitellogenin (VTG). In the MTP complex, conserved structural motifs that form the reciprocal homodimerization interfaces in VTG are re-utilized by MTP to form a stable heterodimer with PDI, which anchors MTP at the site of apoB translocation, and to associate with apoB and initiate lipid transfer. The structural and functional evolution of the VTGs provides a unifying scheme for the invertebrate origins of the major vertebrate lipid transport system.

Amino Acid Sequence↗
PubMed1999

Dynamic contrast enhanced magnetic resonance imaging of the breast is superior to triple assessment for the pre-operative detection of multifocal breast cancer.

BACKGROUND: Inadequately treated multifocal and multicentric disease results in increased local recurrence following breast-conserving surgery. The accurate preoperative diagnosis of multifocal/ centric breast cancer would facilitate the planning of appropriate surgery and prevent reoperation for residual disease. While triple assessment remains the established diagnostic technique, its sensitivity for the diagnosis of multifocal disease remains poor. Dynamic contrast enhanced Magnetic Resonance Imaging (DCE-MRI) of the breast represents an alternative emerging diagnostic modality that has been shown to be highly sensitive for the delineation of primary breast cancer. The aim of this study was to prospectively compare the diagnostic accuracy of DCE-MRI of the breast with conventional triple assessment for the preoperative diagnosis of multifocal/centric breast cancer. METHODS: Patients were recruited from the symptomatic breast clinics. All patients underwent standard triple assessment and DCE-MRI. The MRI scans were reported by a single radiologist blinded to the results of the triple assessment. Surgery was then planned accordingly to all available scan results and the specimens examined by a single pathologist. All patients who did not undergo surgery have been followed up for a minimum of 18 months. RESULTS: A total of 334 women were recruited. There were 178 (52%) cancers that were histologically confirmed and multifocal/centric breast cancer was diagnosed provisionally by the preoperative investigations in 68 (38%); multifocal n = 33, multicentric n = 35, of these patients. In this group, subsequent histology confirmed multifocal/centric disease in 50 (73.5%): multifocal n = 15, multicentric n = 35. Unifocal cancer was found in 15 (22%) and benign disease in 3 (4.4%). The resultant sensitivity, specificity, positive, and negative predictive values were 18%, 100%, 100%, and 76% for triple assessment and 100%, 86%, 73%, and 100% for DCE-MRI. CONCLUSION: DCE-MRI identified a subgroup of breast cancer patients with multifocal/centric disease not evident on standard triple assessment. MRI of the breast should be considered for the preoperative planning of surgery for primary breast cancer.

Aged↗
PubMed1999

Response patterns to repeated CO2 inhalation in individuals with high anxiety sensitivity.

The present report extends previous work which has documented two distinct response patterns to repeated presentation of interoceptive cues (using CO2 inhalation) in PD patients [Beck, J. G. & Shipherd, J. C. (1997). Repeated exposure to interoceptive cues: does habituation of fear occur in panic disorder patients? Behaviour Research and Therapy, 35, 551-557]. We were interested in determining if these two patterns of fear habituation and sensitization would be noted in panic-naive individuals who reported high levels of Anxiety Sensitivity. A second aspect of this report examined whether attention to bodily sensations versus to neutral material would impact fear habituation and sensitization. Participants included 43 panic-naive individuals who scored at least 1 standard deviation above norms on the Anxiety Sensitivity Index. Results indicated that 37% of the sample reported habituation of fear, 47% reported fear sensitization and 16% demonstrated relatively stable fear levels across 12 inhalations of CO2 during session 1. The attentional manipulation did not exert a pronounced influence on anxiety, panic symptom severity, skin conductance, or heart rate in either Habituators or Sensitizers during session 2. These results are discussed in light of their relevance in understanding fundamental psychopathological processes underlying Panic Disorder.

Adult↗
PubMed1999

Prospective comparison of standard triple assessment and dynamic magnetic resonance imaging of the breast for the evaluation of symptomatic breast lesions.

OBJECTIVE: To compare the sensitivity and specificity of the traditional triple assessment of symptomatic breast lesions with contrast-enhanced dynamic magnetic resonance imaging. BACKGROUND: Although triple assessment is currently the gold standard for the assessment of symptomatic breast disease, its specificity is such that open biopsies are still required in many cases to be confident of the diagnosis. Contrast-enhanced dynamic magnetic resonance imaging of the breast represents an alternative diagnostic modality. METHODS: Patients were recruited from the symptomatic breast clinics. If any of the diagnostic modalities suggested malignancy, the lesion was excised. The remaining patients were followed clinically and radiologically. RESULTS: Two hundred eighty-five patients with a mean age of 43 years (range 21 to 77) were recruited. Malignant lesions were excised in 131 patients and benign lesions in 55 patients. The 99 patients who did not undergo surgery were followed clinically and radiologically for a median of 20 months. The sensitivity of each modality was as follows: clinical examination 84%, mammography 87.6%, fine-needle aspiration cytology 79.1%, triple assessment 99.2%, and magnetic resonance imaging 99.2%. In addition, histologically confirmed multifocal disease was detected in 40 patients on magnetic resonance imaging but in only 9 (22.5%) on mammography. The specificity for the diagnosis of benign disease was as follows: clinical examination 83.1%, ultrasound 88.9%, mammography 86.4%, fine-needle aspiration cytology 97%, triple assessment 59.1%, and magnetic resonance imaging 90.9%. CONCLUSION: Contrast-enhanced dynamic magnetic resonance imaging of the breast is as sensitive and more specific than the combined traditional triple assessment for the diagnosis of malignant breast lesions.

Adult↗
PubMed1999

The molecular structure of an unusual cytochrome c2 determined at 2.0 A; the cytochrome cH from Methylobacterium extorquens.

Cytochrome cH is the electron donor to the oxidase in methylotrophic bacteria. Its amino acid sequence suggests that it is a typical Class 1 cytochrome c, but some features of the sequence indicated that its structure might be of special interest. The structure of oxidized cytochrome cH has been solved to 2.0 A resolution by X-ray diffraction. It has the classical tertiary structure of the Class 1 cytochromes c but bears a closer gross resemblance to mitochondrial cytochrome c than to the bacterial cytochrome c2. The left-hand side of the haem cleft is unique; in particular, it is highly hydrophobic, the usual water is absent, and the "conserved" Tyr67 is replaced by tryptophan. A number of features of the structure demonstrate that the usual hydrogen bonding network involving water in the haem channel is not essential and that other mechanisms may exist for modulation of redox potentials in this cytochrome.

Amino Acid Sequence↗
PubMed1999

Hallucinations, delusions, and thought disorder among adult psychiatric inpatients with a history of child abuse.

OBJECTIVE: The relationship between three positive symptoms of schizophrenia-hallucinations, delusions and thought disorder-and childhood physical and sexual abuse among psychiatric inpatients was investigated. METHODS: From the records of 100 consecutive admissions to an acute psychiatric inpatient unit in a New Zealand general hospital, the records of the 22 patients in which a history of either physical or sexual childhood abuse was mentioned were examined for data on the frequency and content of hallucinations, delusions, and thought disorder. RESULTS: Seventeen of the 22 patients exhibited one or more of the three symptoms. Half of the symptoms for which content was recorded appeared to be related to the abuse. An analysis of the relationships between types of abuse and specific symptoms suggested that hallucinations may be more common than delusions or thought disorder among patients who have been sexually abused, particularly among those who have experienced incest, and that delusions may be more related to having been physically abused. CONCLUSIONS: The study findings confirmed previous findings of a high frequency of auditory hallucinations, particularly command hallucinations to kill oneself, and paranoid ideation among inpatients with a history of abuse. The hypothesis that the hallucinations of abuse survivors are "pseudohallucinations" was not supported.

Adult↗
PubMed1999

The relationship of causal beliefs and contact with users of mental health services to attitudes to the 'mentally ill'.

Programmes to destigmatise 'mental illness' have traditionally been based on the 'mental illness is an illness like any other' metaphor and have been largely unsuccessful. By measuring attitudes towards, and etiology beliefs about, 'mental illness' before and after a series of four undergraduate lectures presenting the psychosocial causes of, and solutions to, severe mental health problems, this study (a) replicated previous studies demonstrating a relationship between biogenetic causal beliefs and negative attitudes towards 'mental patients'; (b) found that following the lectures attitudes improved, particularly around the key variables of dangerousness and unpredictability; and (c) demonstrated that amount of contact with people who had received psychiatric treatment was an even stronger predictor of positive attitudes than acceptance of a psychosocial perspective.

Adolescent↗
PubMed1998

Biofeedback/relaxation training and exercise interventions for fibromyalgia: a prospective trial.

OBJECTIVE: To compare the effectiveness of biofeedback/relaxation, exercise, and a combined program for the treatment of fibromyalgia. METHODS: Subjects (n = 119) were randomly assigned to one of 4 groups: 1) biofeedback/relaxation training, 2) exercise training, 3) a combination treatment, or 4) an educational/attention control program. RESULTS: All 3 treatment groups produced improvements in self-efficacy for function relative to the control condition. In addition, all treatment groups were significantly different from the control group on tender point index scores, reflecting a modest deterioration by the attention control group rather than improvements by the treatment groups. The exercise and combination groups also resulted in modest improvements on a physical activity measure. The combination group best maintained benefits across the 2-year period. CONCLUSION: This study demonstrates that these 3 treatment interventions result in improved self-efficacy for physical function which was best maintained by the combination group.

Activities of Daily Living↗
PubMed1998

Child abuse and severity of disturbance among adult psychiatric inpatients.

OBJECTIVE: The aim of this study was to determine whether childhood abuse is related to severity of psychological disturbance in adulthood, even within an extremely disturbed, predominantly psychotic, population. METHODOLOGY: The medical records of 100 consecutive admissions to an adult psychiatric inpatient unit were examined. Documentation of physical or sexual abuse as a child was recorded together with several measures of severity of pathology including: suicidality, length of current admission, age at first admission and use of Intensive Care Unit and Mental Health Act. RESULTS: The study revealed relationships between childhood sexual or physical abuse and suicidality, duration of hospitalization, and age at first admission. Several gender differences in these relationships were found. These included the finding that sexually abused males, but not sexually abused females, were significantly more suicidal than their nonabused counterparts. CONCLUSIONS: The theoretical and clinical implications of further evidence that child abuse is related to the most severe levels of dysfunction in adulthood, including psychosis, are discussed. The need for routine child abuse inquiry in inpatient settings is reiterated.

Adult↗
PubMed1998

Abuse histories of psychiatric inpatients: to ask or not to ask?

OBJECTIVE: The literature suggests that a high prevalence of a history of sexual and physical abuse among psychiatric inpatients is found when researchers inquire about abuse directly, but that relatively low rates are found in medical records. This study examined rates of reported abuse among patients who were and were not asked about abuse at admission. METHODS: The medical records of 100 consecutive admissions to an urban general hospital in New Zealand were examined after the introduction of a new admission form with a section inquiring about abuse. Use of the new admission form was recommended but not mandatory. RESULTS: The abuse section of the new form was completed for only 17 of the 53 patients with whom the new form was used. Review of the medical records of all 100 consecutive admissions revealed a prevalence rate of 32 percent for one or more of the four types of abuse. However, 14 of the 17 patients (82 percent) who were asked directly about abuse reported having experienced abuse. Nonsignificant trends suggested that male gender and being more disturbed or disturbing may be negatively related to the probability of being asked about abuse. Men may be particularly unlikely to disclose childhood abuse if not asked directly. CONCLUSIONS: The authors recommend including inquiry about abuse in standardized admission procedures and providing inpatient staff with training in how and when to ask patients about abuse and how to effectively follow up affirmative responses.

Adult↗
PubMed1998

Measuring consumer participation in mental health services: are attitudes related to professional orientation?

This study describes the development of the Consumer Participation Questionnaire to measure consumer involvement in the planning, management and evaluation of mental health services, and the attitudes of mental health workers towards consumer participation. Results indicate that while most professionals view the concept positively, progress may be occurring faster at the level of individual treatment than at the organisational level. Professionals with a more biological (as opposed to psychosocial) orientation were less likely to predict that services would improve if consumers were involved in the planning of services or were employed therein. Recommendations to facilitate more effective consumer participation are made, including the need for the value of a collaborative approach to be emphasised in professional training programmes.

Adult↗
PubMed1998

Staff response to abuse histories of psychiatric inpatients.

OBJECTIVE: In the context of numerous studies demonstrating that a significant proportion of psychiatric inpatients have been sexually or physically abused at some point in their lives this study ascertained the responses of staff in a psychiatric inpatient unit to knowledge that patients had been subjected to sexual or physical abuse, in childhood or adulthood. METHOD: The medical records of 100 consecutive admissions were examined. Staff response was measured in terms of: (i) acquiring information about previous treatment for, or disclosure of, abuse; (ii) providing information, support or counselling during hospitalisation; (iii) reporting to legal authorities; and (iv) referring for ongoing abuse counselling. RESULTS: Of the 32 patients who were documented as having disclosed abuse 11 files included documentation of previous treatment or disclosure; none were reported to have received support, counselling or information while in hospital; and three referrals were made for ongoing counselling. None of the 52 separate instances of abuse were reported to the authorities. Demographic, diagnostic, clinical and treatment variables, as well as the four abuse categories, were analysed for possible linkage to probability of staff response in each of the four response categories. CONCLUSIONS: It was hypothesised that the low staff response rate is not unique to the particular unit evaluated here. Recommendations are offered regarding the need for unit policies ensuring routine abuse inquiry and for staff training about how to respond to abuse disclosures.

Adult↗
PubMed1997

Radiographic evaluation of breech presentation: is it necessary?

The purpose of this study was to evaluate the use of ultrasound in identifying fetal position and cervical spine flexion in breech presentations. Radiographic and ultrasonographic determinations of the type of presentation (frank, complete or incomplete) and degree of cervical spine flexion in 52 breech presentations were compared. The angle of flexion was defined as the angle between the fetal mandible and main axis of the cervical spine and categorized as full flexion, military, partial extension and full extension. Ultrasound was concordant with radiographic assessment of the type of presentation in 77% and the angle of flexion in 64% of the subjects and was even more accurate in those in labor. All cases predicted as having full flexion (< 90 degrees C) of the cervical spine by ultrasound had an angle of flexion < or = 90 degrees C on radiographic assessment. Of subjects in labor, ultrasound accurately identified the type of breech presentation in all cases. In addition, sonographic identification of full flexion of the cervical spine excludes cases of fetal neck extension and precludes the need for radiographic assessment prior to a trial of labor.

Adult↗
PubMed1997

The relationship between serum human immunodeficiency virus type 1 (HIV-1) RNA level, CD4 lymphocyte percent, and long-term mortality risk in HIV-1-infected children. National Institute of Child Health and Human Development Intravenous Immunoglobulin Clinical Trial Study Group.

Association of human immunodeficiency virus type 1 (HIV-1) RNA level, CD4 cell percent, and mortality was examined in stored sera from 254 infected children in an intravenous immunoglobulin infection prophylaxis trial. Ninety-two children (36.2%) died (41 during the study, 51 during long-term follow-up). The geometric mean baseline HIV-1 RNA level was 104,626 copies/mL, and the mean CD4 cell percent was 25%. Relative risk of death (RR) was 2.1 if the baseline RNA level was >100,000 copies/mL (95% confidence interval [CI], 1.4-3.0) and was 3.0 if the baseline CD4 cell percent was <15% (95% CI, 2.2-4.0). If RNA levels increased after baseline, the RR was 1.8 (95% CI, 1.3-2.6), and if the CD4 cell percent dropped to <15%, the RR was 2.8 (95% CI, 1.6-4.9). In a multivariate model, both baseline RNA level and CD4 cell percent were independently associated with mortality risk. In a time-dependent model, the RR per log10 increase in HIV-1 RNA copy numbers was 2.8 (95% CI, 2.1-3.6) and per 5 percentage point decrement in CD4 cell percent was 1.3 (95% CI, 1.2-1.5). Both variables should be considered for in decision-making regarding therapy and evaluation of antiretroviral response.

AIDS-Related Opportunistic Infections↗