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Biomedical subjects

J Brink

Publications and source records attributed to J Brink.

At least 19 recordsLinked to original sources
PubMed2003

Assessing socio-economic factors in relation to stigmatization, impairment status, and selection for socio-economic rehabilitation: a 1-year cohort of new leprosy cases in north Bangladesh.

The current leprosy elimination strategy focuses almost exclusively on delivery of leprosy diagnostic services and multi-drug treatment (MDT). However, the specific problems of people newly diagnosed with leprosy or cured with MDT primarily relate to impairment of nerve function and social and economic consequences of the diagnosis of leprosy. This study was carried out to investigate the relation between socio-economic factors and the development of nerve impairments and stigma. In addition the relation between socio-economic factors and selection for socio-economic assistance was studied. The study population was a cohort of 2364 newly diagnosed people with leprosy in rural Bangladesh in 1996, including 42.5% women, with an overall mean age of 31.4 years. Three hundred and sixty people (15.2%) had WHO grade 1 or 2 disability identified at diagnosis, and 50 (2.1%) had stigma identified on interview at home visit conducted within one month of diagnosis. One hundred and eighty-eight people (8%) were selected for specific assistance for rehabilitation, primarily interest-free loans for income generating activities or vocational training. Factors independently associated with WHO grade 1 or 2 disability at diagnosis were multibacillary (MB) classification, adult status, and manual occupations. Smear positivity, female sex, and the presence of dependents were associated with an increase in the experience of stigma. The presence of nerve impairments and stigma, as well as several indices of poverty were clearly associated with selection for inclusion in an integrated program for socio-economic assistance. An increased focus by leprosy services on the socio-economic factors associated with poorer physical and social outcomes is recommended. Where adequate finances and trained staff are available, efforts could be made to identify those at higher risk of poor outcomes, and to provide or to mobilize appropriately targeted socio-economic interventions.

Adolescent↗
PubMed2001

Limbic abnormalities in affective processing by criminal psychopaths as revealed by functional magnetic resonance imaging.

BACKGROUND: Psychopathy is a complex personality disorder of unknown etiology. Central to the disorder are anomalies or difficulties in affective processing. METHODS: Functional magnetic resonance imaging was used to elucidate the neurobiological correlates of these anomalies in criminal psychopaths during performance of an affective memory task. RESULTS: Compared with criminal nonpsychopaths and noncriminal control participants, criminal psychopaths showed significantly less affect-related activity in the amygdala/hippocampal formation, parahippocampal gyrus, ventral striatum, and in the anterior and posterior cingulate gyri. Psychopathic criminals also showed evidence of overactivation in the bilateral fronto-temporal cortex for processing affective stimuli. CONCLUSIONS: These data suggest that the affective abnormalities so often observed in psychopathic offenders may be linked to deficient or weakened input from limbic structures.

Adult↗
PubMed2000

Transseptal puncture guided by intracardiac echocardiography during percutaneous transvenous mitral commissurotomy in patients with distorted anatomy of the fossa ovalis.

Positioning of the transseptal needle during percutaneous transvenous mitral commissurotomy (PTMV) can become a difficult and risky procedure when distortion of the interatrial septum exists. We present two cases where intracardiac echocardiography (ICE) facilitated the transseptal puncture in the presence of bulging of the fossa ovalis into the right atrium.

Aged↗
PubMed2000

Report of the Xenotransplantation Advisory Committee of the International Society for Heart and Lung Transplantation: the present status of xenotransplantation and its potential role in the treatment of end-stage cardiac and pulmonary diseases.

An urgent and steadily increasing need exists world-wide for a greater supply of donor thoracic organs. Xenotransplantation offers the possibility of an unlimited supply of hearts and lungs that could be available electively when required. However, anti-body- mediated mechanisms cause the rejection of pig organs transplanted into non-human primates, and these mechanisms provide major immunologic barriers that have not yet been overcome. Having reviewed the literature on xenotransplantation, we present a number of conclusions on its present status with regard to thoracic organs, and we make a number of recommendations relating to eventual clinical trials. Although pig hearts have functioned in heterotopic sites in non-human primates for periods of several weeks, median survival of orthotopically transplanted hearts is currently ,1 month. No transplanted pig lung has functioned for even 24 hours. Current experimental results indicate that a clinical trial would be premature. A potential risk exists, hitherto undetermined, of transferring infectious organisms along with the donor pig organ to the recipient, and possibly to other members of the community. A clinical trial of xeno-transplantation should not be undertaken until experts in microbiology and the relevant regulatory authorities consider this risk to be minimal. A clinical trial should be considered when approximately 60% survival of life-supporting pig organs in non-human primates has been achieved for a minimum of 3 months, with at least 10 animals surviving for this minimum period. Furthermore, evidence should suggest that longer survival (.6 months) can be achieved. These results should be achieved in the absence of life-threatening complications caused by the immunosuppressive regimen used. The relationship between the presence of anti-HLA antibody and anti-pig antibody and their cross-reactivity, and the outcome of pig-organ xenotransplantation in recipients previously sensitized to HLA antigens require further investigation. We recommend that the patients who initially enter into a clinical trial of cardiac xenotransplantation be unacceptable for allotransplantation, or acceptable for allotransplantation but unlikely to survive until a human cadaveric organ becomes available, and in whom mechanical assist-device bridging is not possible. National bodies that have wide-reaching government-backed control over all aspects of the trials should regulate the initial clinical trial and all subsequent clinical xenotransplantation procedures for the foreseeable future. We recommend coordination and monitoring of these trials through an international body, such as the International Society for Heart and Lung Transplantation, and setting up a registry to record and widely disperse the results of these trials. Xenotransplantation has the potential to solve the problem of donor-organ supply, and therefore research in this field should be actively encouraged and supported.

Adult↗
PubMed2000

Ischemic mitral valve repair surgery.

BACKGROUND AND AIM OF THE STUDY: The management of concomitant moderate or severe ischemic mitral regurgitation in the presence of ischemic heart disease is important for long-term prognosis. Mitral repair by either a suture or ring annuloplasty method has been advocated, although clear superiority of either method has not been established. METHODS: Combined coronary artery bypass and mitral valve surgery for ischemic mitral incompetence was performed on 68 consecutive patients between January 1996 and December 1998. The outcome in 63 of these patients (35 females, 28 males) who underwent mitral valve repair was reviewed. RESULTS: Average patient age was 61+/-9.4 years (range: 39-81 years). Average left ventricular ejection fraction (LVEF) was 42.1%; a suture annuloplasty was used in 84% and a ring in 16%. The average number of distal anastomoses was 3.9+/-1.1 (range: 1-6) and aortic cross-clamp time was 131+/-35 min (range: 58-238 min). Operative mortality rate (<30 days or in-hospital) was 12.7% and only requirement for intra-aortic balloon pumping either before or during surgery (21%) was predictive (p<0.05). On discharge, 98.2% of patients were in NYHA class I or II. Follow up (range: 1-35 months) was complete in 95% of cases. Moderate mitral regurgitation on discharge occurred in nine patients and was not related to the type of annuloplasty. Predictive risk factors were preoperative severe mitral regurgitation (p<0.04), poor LVEF (p = 0.05), and was predictive of deterioration of NYHA class (p<0.02), progression of regurgitation (p<0.05), and poor outcome (p<0.01). Poor outcome was also related to surgeon's experience. Structural valvular deterioration occurred in 21.8% of operative survivors, and there was one reoperation and four late deaths. The survival rate (including operative deaths) at 35 months was 68.3 +/- 13.1%, and event-free survival rate (no mortality, reoperation or angina) 65.2+/-6.2%. CONCLUSIONS: The type of annuloplasty used did not influence outcome. The risk of structural mitral valve dysfunction on follow up was related to severe preoperative mitral regurgitation, poor LVEF, surgeon's experience, and was predictive of poor outcome.

Adult↗
PubMed1999

Recombinant immunotoxins directed against the c-erb-2/HER2/neu oncogene product: in vitro cytotoxicity, pharmacokinetics, and in vivo efficacy studies in xenograft models.

TAB-250 and BACH-250 are murine and human chimeric antibodies directed at the extracellular domain of the gp185c-erb-2 (HER2/neu) growth factor receptor overexpressed in a variety of tumor types, including ovarian and breast carcinoma. The ribosome-inhibiting plant toxin gelonin (rGel) was chemically coupled to both antibodies, and the resulting immunotoxins were purified and tested in vitro against human tumor cells expressing various levels of HER-2/neu and in vivo against human tumor xenograft models. The binding of both BACH-250 and BACH-250/rGel conjugate to target cells was essentially equivalent. Against SKOV-3 cells, the IC50 of BACH-250/rGel was 97 pM (17 ng/ml), whereas BACH-250 and rGel alone showed no cytotoxic effects. There was a clear correlation between expression levels of HER-2/neu and cytoimmunotoxin. Tissue distribution studies showed that the antibody and immunotoxin both concentrate 2-10-fold higher in tumors than in normal tissues, with optimal tumor uptake occurring 48-96 h after administration. Plasma clearance curves for BACH-250 and BACH-250/rGel showed terminal-phase half-lives of 26 and 72 h, respectively. In athymic mice bearing s.c. or i.p. SKOV-3 tumors, immunotoxin treatment slowed tumor growth by 99 and 94 % at days 35 and 49 after implantation, respectively, and lengthened the median survival by 40% (from 30 to 50 days) in mice bearing lethal i.p. tumors. We conclude that clinical development of BACH-250/rGel may be warranted in patients with HER2/neu-expressing malignancies.

Animals↗
PubMed1999

Semantic and affective processing in psychopaths: an event-related potential (ERP) study.

We tested the hypothesis that psychopathy is associated with abnormal processing of semantic and affective verbal information. In Task 1, a lexical decision task, and in Task 2, a word identification task, participants responded faster to concrete than to abstract words. In Task 2, psychopaths made more errors identifying abstract words than concrete words. In Task 3, a word identification task, participants responded faster to positive than to negative words. In all three tasks, nonpsychopaths showed the expected event-related potential (ERP) differentiation between word stimuli, whereas psychopaths did not. In each task, the ERPs of the psychopaths included a large centrofrontal negative-going wave (N350); this wave was absent or very small in the nonpsychopaths. The interpretation and significance of these differences are discussed.

Adolescent↗
PubMed1998

Homologue scanning mutagenesis of heregulin reveals receptor specific binding epitopes.

The EGF domain of heregulin has all the receptor binding characteristics of full-length heregulin and has strong homology to the ligands for erbB-1. Despite this, it does not bind erbB-1 but instead binds erbB-3 and erbB-4. The sequence similarity between HRG and the erbB-1 ligands suggest that a few residues are responsible for receptor binding specificity. To determine the sequences involved in receptor binding, we performed homologue scanning mutagenesis on the EGF domain of HRGalpha using sequences of TGFalpha or EGF. We found three sets of mutations in the N-terminal subdomain that were responsible for receptor binding specificity. Mutations in the C-terminal subdomain affected the binding affinity, but did appear to confer any specificity.

Adenocarcinoma↗
PubMed1998

Negative cooperativity between alpha 3 beta 1 and alpha 2 beta 1 integrins in human mammary carcinoma MDA MB 231 cells.

The alpha 3 beta 1 integrin has been implicated as a receptor for several matrix components, including collagen, fibronectin, and laminins. The function of alpha 3 beta 1 seems to be very versatile involving cell adhesion to or migration on ECM, establishment of cell-cell contacts in aggregates, as well as linkage to intracellular tyrosine phosphorylation cascades. Here we report a strong induction of attachment of alpha 3 beta 1 integrin expressing human breast carcinoma cell line MDA MB 231 to matrix proteins by two alpha 3 integrin subunit function-blocking monoclonal antibodies (P1B5 and ASC-1). In contrast, stimulation of adhesion to ECM by inhibitory alpha 3 integrin-specific antibodies was not observed in the alpha 3 beta 1 integrin-expressing nonmalignant human mammary epithelial cell line MCF-10A or the human breast carcinoma cell line MDA MB 468 that expressed relatively low amounts of alpha 3 beta 1 integrin at the cell surface. This increase was specific for collagens and not observed on fibronectin or laminin. Physiological concentrations of bivalent cations were not required. MAb P1B5 did not induce homotypic aggregation of MDA MB 231 cells. The P1B5-induced increase in cell attachment to collagens could be prevented but not reduced below control levels by blocking mAb to the alpha 2 integrin subunit. Function blocking anti-alpha 5 integrin subunit mAb was without effect while anti-beta 1-mAb completely abolished adhesion. Our data indicate that negative cooperativity between integrins results in transdominant inhibition of alpha 2 beta 1 function by alpha 3 beta 1 in human MDA MB 231 but not MDA MB 468 tumor cells or nonmalignant MCF-10A cells.

Antibodies, Monoclonal↗
PubMed1998

Electron crystallographic analysis of two-dimensional streptavidin crystals coordinated to metal-chelated lipid monolayers.

Coordination of individual histidine residues located on a protein surface to metal-chelated lipid monolayers is a potentially general method for crystallizing proteins in two dimensions. It was shown recently by Brewster angle microscopy (BAM) that the model protein streptavidin binds via its surface histidines to Cu-DOIDA lipid monolayers, and aggregates into regularly shaped domains that have the appearance of crystals. We have used electron microscopy to confirm that the domains are indeed crystalline with lattice parameters similar to those of the same protein crystallized beneath biotinylated lipid monolayers. Although BAM demonstrates that the two-dimensional protein crystals grown via metal chelation are distinct from the biotin-bound crystals in both microscopic shape and thermodynamic behavior, the two crystal types show similar density projections and the same plane group symmetry.

Adsorption↗
PubMed1998

Evaluation of charging on macromolecules in electron cryomicroscopy.

We describe procedures to assess charging of biological specimens under electron irradiation in an electron cryomicroscope. Charging can be observed by an expansion of the illuminating beam, blurring of electron diffraction patterns and by beam "footprints" on the specimen. Discharging can also be seen in the defocused electron diffraction mode. We investigated the influence of a variety of factors on the magnitude and visibility of charging. A reduction of charging is noticed when part of the adjacent carbon film is included in the irradiated specimen area.

Catalase↗
PubMed1998

Reduction of charging in protein electron cryomicroscopy.

Charging causes a loss of resolution in electron cryomicroscopy with biological specimens prepared without a continuous carbon support film. Thin conductive films were deposited onto catalase crystals prepared across holes using ion-beam sputtering and thermal evaporation and evaluated for the effectiveness of charge reduction. Deposits applied by ion-beam sputtering reduced charging but concurrently resulted in structural damage. Coatings applied by thermal evaporation also reduced charging, and preserved the specimen structure beyond 5 A resolution as judged from electron diffraction patterns and images of glucose-embedded catalase crystals tilted to 45 degrees in the microscope. This study demonstrates for the first time the feasibility of obtaining high-resolution data from unstained, unsupported protein crystals with a conductive surface coating.

Catalase↗
PubMed1997

Pulmonary artery banding: adequacy and long-term outcome.

OBJECTIVE: Pulmonary artery banding remains a palliative option for patients with congenital heart disease and excessive pulmonary blood flow, if there is unfavourable anatomy or frail condition. In contrast to more developed countries, our patients at Red Cross Children's Hospital, Cape Town, often present to medical services late and in poor nutritional condition. We retrospectively reviewed patients undergoing pulmonary artery banding to determine major variables that influenced long-term outcome. METHODS: In a 10-year period ending June 1992, 135 consecutive patients underwent pulmonary artery banding; 89 with ventricular septal defect type non-mixing disorders, and 46 with mixing or complex disorders. The median age was 3.0 months and weight 3.5 kg with 74.8% of patients weighing less than the third percentile (NCHS adapted), and 39.3% had an additional serious medical illness. RESULTS: Pulmonary banding mortality was 8.1%, and was higher in neonates (22.2%), P = 0.04) but was not related to congenital disorder, associated medical illness, or associated coarctation or interrupted aortic arch. The pulmonary band was inadequate at follow-up in 28.9%, which occurred more commonly if banding was necessary before 3 months of age (41.5%, P = 0.003) but was not related to weight, congenital disorder or associated respiratory infection. Sixty patients (44.4%) have now proceeded to definitive repair with a mortality of 23.3%, which was increased if the pulmonary band was inadequate at the time of definitive repair (44.4%: P = 0.02), but was not related to the congenital disorder. CONCLUSIONS: An inadequate pulmonary artery band adversely affects outcome and demands further aggressive management prior to definitive repair.

Cause of Death↗
PubMed1997

Interaction between panel reactive antibodies, auto- and cold reactive antibodies, and a positive B cell cross-match in renal and cardiac allograft survival.

We analyzed the influence on allograft survival of pretransplant panel reactive antibodies (PRA) < 10%, PRA > 10%, autoantibodies, cold antibodies and a positive B cell crossmatch in 807 renal and 237 cardiac transplant recipients. Donors and recipients were predominantly of mixed ancestry (Khoi, San, Xhosa and Caucasoid). Log rank analysis showed that PRA < 10%, cold antibodies, and a positive B cell cross-match did not influence allograft survival. Autoantibodies were present only in renal recipients; they appeared to have a beneficial effect on allograft survival (P = 0.06). PRA > 10% appeared to have a detrimental effect on allograft survival in both renal (P = 0.07) and cardiac (P = 0.06) recipients. Since autoantibodies and PRA > 10% had opposing effects, the results of renal recipients were reanalyzed after omission of the recipients with autoantibodies and coexisting PRA > 10%. This resulted in augmentation of the protective effect for autoantibodies (P = 0.027) and of the detrimental effect for PRA > 10% (P = 0.020). Two-year survival curves showed that when autoantibodies coexisted with PRA > 10%, the long term, but not the short-term, detrimental effect of PRA > 10% was attenuated. Patients with a positive B cell cross-match clustered in the PRA > 10% group in both renal (PRA negative vs. PRA < 10%; P = 0.0251; PRA < 10% vs. PRA > 10%: P = 0.0011) and cardiac (PRA negative vs. PRA > 10%: P = 0.0085) recipients. We conclude that PRA > 10% is the best indicator to identify recipients at high risk for rejection, and that the influence of antibodies on graft survival can not reliably be established without taking coexisting antibodies into account.

Antilymphocyte Serum↗