Brief report: rifampin-resistant tuberculosis in a patient receiving rifabutin prophylaxis.
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Biomedical subjects
Publications and source records attributed to C Page.
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Nurses' knowledge of the help they can offer women being treated for depression are primarily based on models borrowed from other disciplines rather than on those from nursing itself. Using Orem's nursing model (1991), this comparative, descriptive study (a) described the requisites for self-care, according the value ascribed to them by women being treated for depression; (b) compared these to those of women not being treated for an emotional problem; and (c) identified the types of assistance that would fulfil the self-care requisites perceived by women being treated for depression. The results indicated that, compared to women not being treated (n = 30), those being treated (n = 30) ascribed significantly higher values to self-help requisites related to assertiveness, mood, and self-esteem. In contrast, women in the comparison group attributed more importance to various means of improving their interpersonal relations. Women being treated for a depressive episode felt they needed assistance in areas mainly related to self-esteem, mood, and knowledge of depression to fulfil their self-care requisites. Only rarely did they consider the nurse or social network to be valuable sources of help. The implications of these results for nursing interventions is discussed. Recommendations are made on directions for further research.
Cell surface heparan sulfate proteoglycans, such as the syndecans, are required for cellular responses to heparin-binding growth factors and extracellular matrix components. Expression of syndecan-1 and -4 is induced in mesenchymal cells during wound repair in the mouse, consistent with a role for syndecans in regulating cell proliferation and migration in response to these effectors. Here we show that wound fluid contains inductive activity that mimics the in vivo induction in time of appearance, specificity for mesenchymal cells, and selectivity for syndecan-1 and -4. We have purified and synthesized a 4.8-kDa proline-rich protein from wound fluid that reproduces this induction of syndecan-1 and -4 in cultured cells. This peptide, identical to the antibacterial peptide PR-39, is released into the wound by the cellular infiltrate and induces syndecan expression at the same peptide concentrations that lyse bacteria. These results indicate that wounds contain a multifunctional protein that induces mammalian cells to express cell surface heparan sulfate proteoglycans as part of the wound repair process and that kills bacteria as part of a nonimmune defense mechanism.
Theophylline, in addition to its bronchodilator effect, may attenuate inflammation in asthma. We did a double-blind placebo-controlled study of the effect of oral theophylline on the inflammatory response of the bronchial mucosa to inhalation of allergen in 19 atopic asthmatic subjects. Bronchoscopy and bronchial biopsy were done 24 hours after allergen inhalation before and after six weeks of treatment with oral slow-release theophylline, 200 mg 12 hourly. The mean serum concentration was 36.6 mumol/L, which is below the currently-accepted therapeutic range. After treatment with theophylline there was a significant reduction in the number of EG2-positive activated eosinophils (5.9 before and 2.1 after treatment, Wilcoxon signed rank p < 0.05) and total eosinophils (16.7 before and 7.6 after treatment, p < 0.05) beneath the epithelial basement membrane. We conclude that low-dose oral theophylline attenuates airway inflammatory response to allergen inhalation in atopic asthma.
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It is accepted that T cells require at least two signals to undergo proliferation and cytokine release: an antigen dependent signal mediated via the the TCR (T cell receptor) and an antigen independent signal mediated via one or more accessory or adhesion molecules. Interaction between CD28 or CTLA-4 and the B7 co-receptors found on many antigen presenting cells (APC) is known to be essential for antigen specific (including alloantigen) expansion of T cells in vitro and in vivo. CTLA-4-Ig is a fusion protein with very high affinity for B7. It has been used in vivo to block both allograft and xenograft rejection. Most of the work investigating second signal requirement has used 'professional' APC. In view of the observations that class II positive human endothelial cells can cause direct allostimulation of resting CD4+ and CD8+ T cells, we have investigated the requirement of CTLA-4 in this response. The current studies show that the proliferative response of allogeneic CD4+ and CD8+ T cells to interferon-gamma treated HUVEC (human umbilical vein endothelial cells) is inhibited by monoclonal antibodies (mAbs) against MHC class II and class I antigens, respectively, but not by CTLA-4-Ig. In contrast, lymphocytes proliferating in response to allogeneic splenocytes are inhibited by CTLA-4-Ig. Cell surface binding studies using flow cytometry demonstrated failure of endothelial cells to bind either CTLA-4-Ig or mAbs against B7 receptors. In conclusion, different APC use different co-stimulatory signals. The possibility that this leads to different cytokine profiles needs to be investigated to further understand the role of endothelial cells in transplant rejection.
OBJECTIVE: The aim was to study pathways of nucleotide catabolism and adenosine production in cultured human umbilical vein endothelial cells (HUVEC) incubated under normal conditions and following inhibition of ATP synthesis. METHODS: Confluent cultures of HUVEC were incubated for 45 min in Hank's balanced salt solution in a 95% O2/5%CO2 atmosphere under the following experimental conditions: (1) in presence of the adenosine deaminase inhibitor, erythro-9(2-hydroxy-3-nonyl) adenine (EHNA); (2) with EHNA and the adenosine kinase inhibitor, 5'-iodotubercidin (ITu); (3) with iodoacetate and oligomycin (I+O), inhibitors of ATP production, and EHNA; (4) with I+O, EHNA, and an inhibitor of ecto 5'-nucleotidase, alpha, beta-methyleneadenosine 5'-diphosphate (AOPCP). Nucleotide and catabolite contents in both cells and medium were analysed by HPLC. RESULTS: The initial contents of ATP, ADP, and AMP were 9.12(SEM 1.2), 0.73(0.08) and 0.11(0.02) nmol per culture flask respectively. These levels were maintained under experimental condition (1), with only a small increase in hypoxanthine in the medium of 0.9(0.2) nmol. Under experimental condition (2), adenosine accumulation in the medium was greatly enhanced [increase by 0.9(0.2) nmol], while the rise in hypoxanthine was similar to that in experimental condition (1). Under experimental condition (3), cellular ATP was totally depleted after 45 min and AMP increased to 4.3(0.9) nmol. Adenosine in the medium was increased by 5.4(0.2) nmol, the increase in the sum of hypoxanthine and inosine was 1.6(0.2) nmol, and the increases in uric acid and xanthine were less than 0.4 nmol. Under experimental condition (4), where AOPCP was present in addition to I+O and EHNA, adenosine production was markedly reduced and AMP accumulated in the medium [1.2(0.2) nmol]. CONCLUSIONS: Adenosine is generated continuously in cultured HUVEC under normal conditions, but is immediately recycled via adenosine kinase. In ATP depleted cells, nucleotide catabolism proceeds predominantly via intracellular dephosphorylation of AMP with a small contribution from the extracellular dephosphorylation pathway. The capacity of the AMP deamination pathway in endothelium is small and the flux through xanthine oxidoreductase is minimal.
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Coordination of marrow donation for allogeneic BMT is a common logistical problem. The use of cryopreserved donor marrow would facilitate scheduling and avoid potential problems due to donor employment, injury, infection or death. We analysed results of 10 matched related BMTs performed with cryopreserved donor marrow and compared them with 33 matched related BMTs using fresh bone marrow over a 4 year period. No difference in time to engraftment of granulocytes and platelets or transfusion requirements were demonstrated for the two groups. However, there was less GVHD in patients who received cryopreserved donor marrow (chi 2, p = 0.03; Fisher's exact test (two-sided) p = 0.067) despite comparable risk factors. The reason for this difference is unclear. Our results indicate that the use of cryopreserved bone marrow for allogeneic BMT patients is at least equivalent to the use of fresh bone marrow. A prospective randomized trial is needed to determine if a true difference exists in the incidence or severity of acute GVHD and to determine if recurrence rate is different between the two groups.
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The antigenic status of vascular endothelium from different sites of the normal adult and fetal human cardiovascular system was investigated. Tissues included aorta (n = 9), pulmonary artery (n = 8), coronary artery (n = 6), ventricle/atrium (n = greater than 10), lymph node (n = 2), fetal whole heart (n = 3), and umbilical cord (n = 7). Frozen sections were studied using monoclonal antibodies recognizing endothelial markers (EN4, vWf, Pal-E, and 44G4), vascular adhesion molecules (ICAM-1, ELAM, VCAM, and PECAM), the monocyte/endothelial marker (OKM5), and major histocompatibility complex (MHC) molecules (class I and class II). Results demonstrate that capillary endothelium is phenotypically different from endothelial cells (EC) lining large vessels. Capillary EC strongly express MHC classes I and II, ICAM, and OKM5, which are variably weak to undetectable on large vessels. In contrast, the large vessels strongly express vWf and appear to constitutively express ELAM-1. This suggests that the capillary EC may be more efficient at antigen presentation or more susceptible to immune attack in vivo. Interestingly, normal coronary arteries, unlike all other large vessels, express MHC class II and VCAM molecules. Future studies should concentrate on comparative functional studies between capillary, coronary, and large vessel EC.
NTera 2/cl.D1 (NT2) cells, a human teratocarcinoma cell line, were manipulated following retinoic acid treatment to yield greater than 95% pure cultures of neuronal cells (NT2-N cells). The commitment of NT2-N cells to a stable neuronal phenotype is irreversible as judged by the lack of mitotic activity or phenotypic reversion over a period of 2 months in culture. Furthermore, NT2-N cells express a variety of neuronal markers including many neuronal cytoskeletal proteins, secretory markers, and surface markers. NT2-N cells resemble primary neuronal cultures from rodents morphologically and in density of process outgrowth and, like primary neurons, go on to elaborate processes that differentiate into axons and dendrites. This culture method yields sufficient highly differentiated postmitotic NT2-N cells for both biochemical and molecular biological studies. Indeed, when undifferentiated NT2 cells were stably transfected with a beta-galactosidase (beta-gal) expression plasmid, beta-gal expression was shown to be present in both undifferentiated NT2 and postmitotic NT2-N cells. Thus, the ability to transfect expression plasmids into undifferentiated NT2 cells will allow the introduction of normal and mutant gene products into cells that can then be induced to become stable, postmitotic human neurons. We conclude that NT2 cells and NT2-N cells represent a unique model system for studies of human neurons, and a novel vehicle for the expression of diverse gene products in terminally differentiated polarized neurons.
Immunocytochemical analysis of endomyocardial biopsies from cardiac transplant patients has defined changes in expression of antigens, expressed on both the myocardium and endothelium which are characteristic of rejection. Biopsies taken from normal donor heart (prior to transplantation) have been compared with biopsies showing histological signs of rejection. There is induction of MHC class I antigen on the normally negative myocardial plasma membrane and induction of the adhesion molecule ICAM-1 on the intercalating discs. Capillary endothelial cells, which constitutively express Class II DR antigen and ICAM-1 in normal heart show increased of endothelial antigens Pal-E and FVIII-RA during rejection. These results demonstrate perturbation of the endothelial system during rejection and possibly indicate damage to the capillary endothelial cells.
The half-time of transfer of 99mTc DTPA (T50) is a useful method of assessing lung epithelial permeability, which has been shown to be altered in patients with acquired immunodeficiency syndrome (AIDS) who have Pneumocystis carinii pneumonia (PCP). The present study was designed to assess the usefulness of the T50 measurement in evaluating patients with renal transplants, breathlessness, and fever. An assessment was also made of the effect of renal failure on the T50 result. Sixty-eight non-smokers (12 normal subjects, ten patients with chronic renal failure not requiring dialysis (CRF), ten patients on haemodialysis (HD), ten patients on chronic ambulatory peritoneal dialysis (CAPD), 13 patients with functioning renal transplants (Tx), seven transplanted patients with PCP, two transplanted patients with cytomegalovirus pneumonia, and four transplanted patients with other lung infections), and 30 smokers (ten normal subjects, five CRF, five HD, five CAPD, five Tx) were studied. The lung epithelial permeability of the patients with renal failure, as judged by the whole lung T50, was not significantly different from that of the normal subjects. The T50 of transplanted smokers was significantly longer than that of the normal subjects who smoked and not significantly different from the transplanted non-smokers. Patients with PCP and CMV pneumonitis had significantly faster T50 values compared with all other patients with renal disease. This fast T50 suggests that the test may be of use in identifying patients who have an alveolitis as a cause for their fever when immunosuppressed following a renal transplant.