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Biomedical subjects

P Becker

Publications and source records attributed to P Becker.

At least 73 records · Page 4Linked to original sources

Chiaroscuro hematopoietic stem cell.

These observations suggest several immediate clinical strategies. In gene therapy, approaches could be targeted to obtain cycling of hematopoietic stem cells and gene-carrying retrovirus vector integration followed by engraftment at an appropriate time interval which favors engraftment. The same type of approach can be utilized for stem cell expansion approaches. Alternatively marrow or peripheral stem cell engraftment can be obtained with minimal to no toxicity in allochimeric strategies in such diseases as sickle cell anemia or thalassemia. A similar approach could be useful in obtaining cell engraftment with minimal toxicity in therapies employing cellular immune (T-cell and NK-cell) attack against cancer. These areas of clinical application are outline in Table 3.

Animals↗

Intracoronary application of C1 esterase inhibitor improves cardiac function and reduces myocardial necrosis in an experimental model of ischemia and reperfusion.

BACKGROUND: Myocardial injury from ischemia can be aggravated by reperfusion of the jeopardized area. The precise underlying mechanisms have not been clearly defined, but proinflammatory events, including complement activation, leukocyte adhesion, and infiltration and release of diverse mediators, probably play important roles. The present study addresses the possibility of reducing reperfusion damage by the application of C1 esterase inhibitor (C1-INH). METHODS AND RESULTS: Cardioprotection by C1-INH 20 IU/kg IC was examined in a pig model with 60 minutes of coronary occlusion, followed by 120 minutes of reperfusion. C1-INH was administered during the first 5 minutes of coronary reperfusion Compared with the NaCl controls, C1-INH reduced myocardial injury (48.8 +/- 7.8% versus 73.4 +/- 4.0% necrosis of area at risk, P < or = .018). C1-INH treatment significantly reduced circulating C3a and slightly attenuated C5a plasma concentrations. Myocardial protection was accompanied by reduced plasma concentration of creatine kinase and troponin-T. C1-INH had no effect on global hemodynamic parameters, but local myocardial contractility was markedly improved in the ischemic zone. In the short-axis view, 137 degrees of the anteroseptal region showed significantly improved wall motion at early and 29 degrees at late reperfusion with C1-INH treatment. CONCLUSIONS: C1-INH significantly protects ischemic tissue from reperfusion damage, reduces myocardial necrosis, and improves local cardiac function.

Anaphylatoxins↗

Determination of the kinetic parameters during continuous cultivation of the lipase-producing thermophile Bacillus sp. IHI-91 on olive oil.

A thermostable lipase was produced in continuous cultivation of a newly isolated thermophilic Bacillus sp. strain IHI-91 growing optimally at 65 degrees C. Lipase activity decreased with increasing dilution rate while lipase productivity showed a maximum of 340 U l-1 h-1 at a condition rate of 0.4 h-1. Lipase productivity was increased by 50% compared to data from batch fermentations. Up to 70% of the total lipase activity measured was associated to cells and by-products or residual substrate. Kinetic and stoichiometric parameters for the utilisation of olive oil were determined. The maximal biomass output method led to a saturation constant Ks of 0.88 g/l. Both batch growth data and a washout experiment yielded a maximal specific growth rate, mu max, of 1.0 h-1. Oxygen uptake rates of up to 2.9 g l-1 h-1 were calculated and the yield coefficient, Y X/O, was determined to be 0.29 g dry cell weight/g O2. From an overall material balance the yield coefficient, Y X/S, was estimated to be 0.60 g dry cell weight/g olive oil.

Bacillus↗

Short-term antihypertensive medication does not exacerbate sleep-disordered breathing in newly diagnosed hypertensive patients.

It has been speculated for some time that various antihypertensive medications may have a deleterious effect on respiration during sleep and thereby enhance the apparent association between hypertension and sleep apnea/hypopnea (SAH). However, there are few data to support this contention. The present study used a double-blind, randomized, cross-over design to contrast the effects of 6 weeks treatment with alpha-methyldopa and the combination of hydrochlorothiazide and amiloride with that of amlodipine and the combined diuretics in a group of 24 newly diagnosed patients with primary hypertension. All-night polysomnography was performed before the initiation of therapy (baseline) and at the end of the two treatment periods. Respiratory variables failed to reveal any significant differences between the treatments and baseline, or between the two different treatment regimens. The two treatment regimens achieved similar reductions in blood pressure. The prevalence of SAH was 25% before treatment, which is comparable to a prevalence of 20% in a similar group drawn from the same population but receiving various antihypertensive medications. The findings of this study are in agreement with previous reports using other classes of antihypertensive drugs that also failed to detect any tendency for increases in nocturnal respiratory disturbance indices over assessment periods of 8 weeks or shorter.

Amlodipine↗

A unified nomenclature for sap flow measurements.

A unified nomenclature for use in heat pulse measurement of sap flow is proposed. This unified nomenclature overcomes fundamental misunderstandings of the physics of heat and sap movement in wood. The nomenclature is also appropriate to other methodologies for sap flow measurement, such as heat balance methods.

Journal Article↗

The cost and benefit of prophylaxis against deep vein thrombosis in elective hip replacement. DVT/PE Prophylaxis Consensus Forum.

UNLABELLED: A consensus forum was convened to evaluate the economic considerations associated with prophylaxis against thrombo-embolic disease in patients undergoing hip replacement therapy in South Africa. This forum consists of orthopaedic surgeons, vascular surgeons and a statistician. METHODS: The forum was instructed to evaluate the economic costs of the commonly used forms of prophylaxis of thrombo-embolism in patients undergoing hip replacement surgery in South Africa, looking at short-term events only. The methods used for the prophylaxis of thrombo-embolism in South Africa were determined by a postal survey. A decision tree was constructed to determine the events that will occur after a clinical decision to use no prophylaxis. The probabilities of these events were then determined. Protocols for and costs of prophylaxis and treatment were established. With the decision tree and these costs, the cost of the various modalities of prophylaxis was then determined. RESULTS: The probability, determined by the forum, of developing a deep-vein thrombosis (DVT) when no prophylaxis is used was 0.5, with a mortality rate of 2.1%. The cost of this decision was R875. No prophylaxis given, but a venogram performed on day 7, reduced the mortality rate to 0.7%; however, this cost R3 017. The cost of low-molecular-weight heparin was R1 223 (probability 0.26, mortality rate 1.1%), while unfractionated heparin with a graduated compression stocking (GCS) cost R1 351 (probability 0.24, mortality rate 1%). Aspirin with a GCS cost R777 (probability 0.35, mortality rate 1.5%).

Anticoagulants↗

Functional analysis of retinoid Z receptor beta, a brain-specific nuclear orphan receptor.

The retinoid Z receptor beta (RZR beta), an orphan receptor, is a member of the retinoic acid receptor (RAR)/thyroid hormone receptor (TR) subfamily of nuclear receptors. RZR beta exhibits a highly restricted brain-specific expression pattern. So far, no natural RZR beta target gene has been identified and the physiological role of the receptor in transcriptional regulation remains to be elucidated. Electrophoretic mobility shift assays reveal binding of RZR beta to monomeric response elements containing the sequence AnnTAGGTCA, but RZR beta-mediated transactivation of reporter genes is only achieved with two property spaced binding sites. We present evidence that RZR beta can function as a cell-type-specific transactivator. In neuronal cells, GaI-RZR beta fusion proteins function as potent transcriptional activators, whereas no transactivation can be observed in nonneuronal cells. Mutational analyses demonstrate that the activation domain (AF-2) of RZR beta and RAR alpha are functionally interchangeable. However, in contrast to RAR and TR, the RZR beta AF-2 cannot function autonomously as a transactivation domain. Furthermore, our data define a novel repressor function for the C-terminal part of the putative ligand binding domain. We propose that the transcriptional activity of RZR beta is regulated by an interplay of different receptor domains with coactivators and corepressors.

3T3 Cells↗

Self-organization of microtubules into bipolar spindles around artificial chromosomes in Xenopus egg extracts.

Functional nuclei and mitotic spindles are shown to assemble around DNA-coated beads incubated in Xenopus egg extracts. Bipolar spindles assemble in the absence of centrosomes and kinetochores, indicating that bipolarity is an intrinsic property of microtubules assembling around chromatin in a mitotic cytoplasm. Microtubules nucleated at dispersed sites with random polarity rearrange into two arrays of uniform polarity. Spindle-pole formation requires cytoplasmic dynein-dependent translocation of microtubules across one another. It is proposed that spindles form in the absence of centrosomes by motor-dependent sorting of microtubules according to their polarity.

Animals↗

Effect of HLA-DR3 gene expression on cadaveric renal allograft survival in blacks.

The effect of HLA-DR3 gene expression was studied in black cadaveric renal allograft recipients of organs from the same donor race. From January 1984 to June 1992, 70 patients received cadaveric renal allografts at the Medical University of Southern Africa (MEDUNSA). The average age and F:M ratio was 30 years and 1: 1.2 respectively. HLA-A, B and DR matching was zero to one in 80%. Actuarial graft survival at yearly intervals in 22 HLA-DR3 gene expressors was 62, 55, 38, 30 and 24% as compared to 82, 78, 70, 64 and 58% in 48 non-HLA DR3 gene expressors (Breslow p = 0.01 and Mantel-Cox p = 0.05). There was no statistical differences in creatinine values associated with HLA-DR3 gene expression during the 1st year after transplantation. Renal allografts were lost from rejection in 9 out of 16 HLA-DR3 gene expressors as compared to 19 out of 29 non-HLA DR3 gene expressors (Fisher's exact test p = 0.8). HLA-DR3 gene expression is a risk factor for earlier graft loss in black South Africans.

Adolescent↗

[Pulmonary thromboendarterectomy: a case of surgical treatment of chronic pulmonary thromboembolism under circulatory arrest with deep hypothermia].

Pulmonary thromboendarterectomy under circulatory arrest and deep hypothermia is presently a curative treatment for pulmonary hypertension secondary to chronic pulmonary artery thromboembolic occlusion, but is still not frequently performed around the world. We report here the first successful pulmonary thromboendarterectomy under circulatory arrest performed in Chile. The patient was a 37 year old white man, high school teacher, with a 5 months history of effort dyspnea and cough. Pulmonary hypertension secondary to chronic pulmonary thromboembolism was confirmed by angiography and echocardiography. The patient was operated on April 27, 1995. After the operation the patient had an immediate and maintained normalization of his pulmonary hemodynamics. He presented periods of delirium that postponed mechanical ventilation disconnection until the 7th postoperative day, after which he had an uneventful neurological recovery. Before hospital discharge a control angiography showed complete patency of the pulmonary artery system with no evidence of residual thrombi. Presently he is enjoying a normal life and back to his teaching activities.

Adult↗

Functional antagonism between the retinoic acid receptor and the viral transactivator BZLF1 is mediated by protein-protein interactions.

The Epstein-Barr virus-encoded protein BZLF1 is a member of the basic leucine zipper (bZip) family of transcription factors. Like several other members of the bZip family, transcriptional activity of BZLF1 is modulated by retinoic acid receptors (RARs). We present evidence that the RAR alpha and BZLF1 can reciprocally repress each other's transcriptional activation by a newly discovered mechanism. Analysis of RAR alpha mutants in transfection studies reveals that the DNA binding domain is sufficient for inhibition of BZLF1 activity. Analysis of BZLF1 mutants indicates that both the coiled-coil dimerization domain and a region containing the transcriptional activation domain of BZLF1 are required for transrepression. Coimmunoprecipitation experiments demonstrate physical interactions between RAR alpha and BZLF1 in vivo. Furthermore, glutathione S-transferase-pulldown assays reveal that these protein-protein interactions are mediated by the coiled-coil dimerization domain of BZLF1 and the DNA binding domain of RAR alpha. While RAR alpha is unable to recognize BZLF1 binding sites, the RAR alpha can be tethered to the DNA by forming a heteromeric complex with BZLF1 bound to DNA. Tethering RARs via protein-protein interactions onto promoter DNA suggest a mechanism through which RARs might gain additional levels of transcriptional regulation.

3T3 Cells↗

Superimposition and reconstruction in forensic facial identification: a survey.

Forensic facial reconstruction, is the reproduction of the lost or unknown facial features of an individual, for the purposes of recognition and identification. It is generally accepted that facial reconstruction can be divided into four categories: (1) replacing and repositioning damaged or distorted soft tissues onto a skull; (2) the use of photographic transparencies and drawings in an identikit-type system; (3) the technique of graphic, photographic or video superimposition; (4) plastic or three-dimensional reconstruction of a face over a skull, using modelling clay. This paper sets out to review work done on both superimposition and plastic reconstruction, however, the authors believe that only the latter category can correctly be termed facial reconstruction. The survey is divided according to work done through anthropological evaluation of the skull, clinical examination and dissection of the soft tissues, as well as methods of measuring soft tissue thicknesses using tissue puncture, ultrasound, cephalometric radiography and magnetic resonance imaging. In addition, a method of the combined use of ultrasound and radiography to collect a wider range of facial soft tissue depths and a method of producing skull and face profiles are outlined.

Anthropometry↗

CD4+ lymphocyte count in African patients co-infected with HIV and tuberculosis.

The objectives of this study were (a) to compare the CD4+ lymphocyte profiles over time of two groups of patients hospitalized for tuberculosis (TB) treatment [a group of patients with TB only (TB group) and a group dually infected by HIV and TB (HIV/TB group)] and (b) to assess the usefulness of the total lymphocyte count (TLC) as a surrogate of the CD4+ lymphocyte count in the HIV/TB group. A total of 345 patients were enrolled in the study of whom 104 (29.8%) were HIV seropositive (HIV/TB). On admission, the CD4+ lymphocyte counts of the HIV/TB cohort were significantly lower than the TB group with medians of 230 (interquartile range, 90-475) and 630 (500-865), respectively (p < 0.0001). The CD4+ lymphocyte count increased significantly in both cohorts on routine TB treatment. A TLC of 1,300-1,500 cells/mm3 was found to be predictive of a CD4+ lymphocyte count of < or = 200 cells/mm3 both on admission and after 1 month of TB therapy. We conclude from this study that the positive influence of TB therapy on the CD4+ lymphocyte count strongly suggests an additional avenue of influence on the course of HIV infection, whereas the usefulness of the TLC as a surrogate estimation of CD4+ lymphocyte count in HIV/TB patients has important implications for the developing world.

AIDS-Related Opportunistic Infections↗

Fecal short chain fatty acids in South African urban Africans and whites.

UNLABELLED: Diminished levels for fecal short chain fatty acids (SCFAs) have been linked to occurrence of ulcerative colitis, colorectal polyps, and colon cancer, diseases that are rare or uncommon in African populations. PURPOSE: The aim of this study was to determine fecal SCFA concentrations and fecal pH values in groups of black South Africans (African) and white South Africans (white) subjects. METHODS: Twenty healthy Africans (all women; mean age, 35 years) and 17 healthy whites (7 women; 10 men; mean age, 32 years) were tested. RESULTS: Mean total concentrations of SCFAs in the two groups were 142.1 (+/- 53.9) and 69.2 (+/- 26.0) mmol/kg wet feces, respectively (P = 0.0001). Mean values for Africans were significantly higher in all subfractions except butyrate. There was a significant inverse correlation between fecal pH value and total fecal SCFA concentration (r = 0.704; P = 0.001). CONCLUSION: High concentrations of fecal SCFAs in the African group could protect against chronic bowel diseases.

Adult↗

Hypertension and sleep apnea in black South Africans. A case control study.

Despite relatively consistent findings that patients with hypertension have higher than anticipated prevalences of sleep apnea/hypopnea (SAH), inadequately controlled factors such as age and obesity have been implicated as possibly accounting for these findings. All-night polysomnograms were performed on 20 hypertensive black South Africans, a group with increased risk for this disease. They were matched with a control group of black subjects in respect of age, gender, body mass index (BMI), neck circumference and scores on a sleep questionnaire. While the groups failed to differ significantly in terms of demographic variables, nor in regard to 8/9 anthropometric measures, the hypertensive group had a significantly higher apnea/hypopnea index (AHI) (P = .01), longer duration of AH (P = .01) and lower mean minimum arterial oxygen saturation levels (P = .005). Of the anthropometric measures, only age and neck circumference were found to be cofactors for AHI and were accounted for in the analysis. Five of the hypertensive patients and two of the controls had an AHI > 10, giving a prevalence odds ratio of 3 (95% confidence interval: 0.66-14.50). The present study appears to be the first in black African subjects and with prevalence findings largely comparable to those obtained in other ethnic groups. There was a trend for more severe SAH to occur in this subgroup of five hypertensives (AHI = 14-30) than in controls (maximum AHI = 12). While data are lacking to link antihypertensive medication to SAH in humans, further study is necessary before discarding this factor.

Adult↗