Acute pancreatitis related to octreotide in a patient with acquired immunodeficiency syndrome.
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Biomedical subjects
Publications and source records attributed to E Muñoz.
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The activity of the NF-kappa B transcription factor is controlled through cytoplasmic retention by either of two types of molecules: the inhibitor I kappa B alpha/MAD3 or the p105 and p100 precursors of the p50 and p52 DNA-binding subunits. Treatment of cells with classical NF-kappa B inducers such as tumor necrosis factor, interleukin-1, phorbol myristate acetate, and lipopolysaccharide results in MAD3 degradation followed by nuclear translocation of NF-kappa B. On the other hand, the mechanisms involved in the dissociation of the cytoplasmic p105/p100-containing complexes are largely unknown. The Tax protein encoded by human T-cell leukemia virus type 1 is a potent activator of viral and cellular gene transcription. It does not bind DNA directly but seems to activate transcription indirectly either by enhancing the activities of the transcription factors that recognize responsive elements located in the promoters of the Tax-responsive genes or by forming ternary complexes with these factors and DNA. It has been previously shown that Tax is able to induce nuclear translocation of NF-kappa B. We demonstrate here that Tax can induce translocation of members of the NF-kappa B family retained in the cytoplasm through their interaction with either p105 or p100. On the other hand, Tax induces no apparent degradation of MAD3, although experiments using cycloheximide indicate that it decreases the half-life of MAD3. However, this activity is shared by a mutant of Tax which is unable to activate NF-kappa B. These results suggest that Tax activates NF-kappa B essentially through the p105/p100 retention pathway.
BACKGROUND: Health care costs continue to spiral; aggregate costs for 1992 are $850 billion, 13.6% of the U.S. gross national product. The issue has assumed national proportions, and change appears to be on the federal agenda. Great interest in surgical expenditures exists, which comprise 30.1% of all health care outlays. METHODS: We analyzed 13,600 general surgical patients in eight teaching hospitals in New Jersey during 1988. Hospital resource consumption was measured for hospital length of stay, hospital cost per patient, race, gender, diagnoses and procedures, and mortality rate. RESULTS: Surgical patients at these medical centers had a mean hospital cost per patient of $8,193, mean hospital length of stay of 12.4 days, an emergency admission rate of 40.4%, and a mortality rate of 6.0%. Emergency admissions had higher costs compared with nonemergencies ($11,717 vs $5,804, p < 0.001) and a poorer outcome (11.2% mortality rate vs 2.6%, p < 0.01). Patients who died had a higher hospital cost per patient compared with survivors ($29,314 vs $6,837, p < 0.001) and a higher emergency admission rate (74.7% vs 38.2%, p < 0.001). CONCLUSIONS: Changes to the surgical delivery system will occur during the next decade. This study showed factors associated with higher hospital costs for surgical patients; changing reimbursement systems must recognize these characteristics for surgical patients in teaching hospitals. Factors associated with emergency admission and mortality, once identified, could be used to improve the health delivery system that affects surgical patients.
OBJECTIVE: To find out how accurate our records are and the state of health of the patients with diabetes mellitus type II (DM) in our Base Health Area (BHA) in Osona county (Barcelona), both before and after introducing a new procedure. DESIGN: Quality control study based on the medical records (PCMR) of DM patients. The evaluation took place between 1.1.90 and 31.12.90; and the re-evaluation between 1.1.91 and 31.12.91, after the DM procedure had been put in place as a corrective measure. PATIENTS: 198 patients: all of those suffering from DM type II. MAIN MEASUREMENTS AND RESULTS: 110 women and 88 men, with an average age of 65.4 +/- 11.9, were under study. We observed from the records of attendance that 94.4% were or had been smokers, whereas the question of the eye fundus was only mentioned in 36.8%. The introduction of a procedure has improved the records in almost every parameter. In 1991, 36.8% of the patients had normal-weight criteria, 33.3% had good biochemical control and 15.6% fulfilled both these criteria. CONCLUSIONS: Those tests which could be performed with few instruments were carried out much better than those which needed more complex technology or specialist support. Arising from this study, the authors propose four indicators of quality control: 1) Weight normality. 2) Annual plasmatic fructosamine. 3) Annual eye fundus check. 4) Annual proteinuria check.
A patient who had a polyneuropathy compatible with a chronic inflammatory demyelinating polyneuropathy and was initially negative for anti-myelin-associated glycoprotein (MAG) antibodies developed a double monoclonal gammopathy, IgM kappa and IgM lambda, two years after the diagnosis. The IgM kappa, but not the IgM lambda, exhibited strong anti-MAG antibody activity. The late appearance of the anti-MAG immunoreactivity suggests that in patients with an initial diagnosis of chronic inflammatory demyelinating polyneuropathy, the search for anti-MAG antibodies should be repeated during the course of the neuropathy.
The levels of CD26 expression, their capacity to induce protein tyrosine phosphorylation and their functional implication in natural killer (NK) cytolysis have been studied. It was found that only a small fraction (12-15%) of peripheral NK cells expresses CD26 compared with the high expression (99%) found in NK clones. The protein tyrosine phosphorylation mediated by means of CD26 activation was studied in NK cells treated with the anti-CD26 MoAb 134-2C2, and two new proteins of 50 and 21 kDa appeared phosphorylated in tyrosine residues. To study the influence of CD26 antigen in NK lysis, we analysed the lytic capacity of NK cells stimulated with different anti-CD26 MoAbs or after separation into CD26+ and CD26- subsets and using K562 as target cells. Under these conditions, no differences were found in the chromium release by the target cells. Redirected lysis through CD16 was also measured by arming the effector cells (CD26+ and CD26-) with anti-CD16 antibody and using K562 as target cells. It was found that CD26- cells showed significantly less CD16-dependent lysis than CD26+ cells. These results indicate that CD26 is related to the CD16-dependent lysis but not to NK cytolysis which may be caused by mediation of protein tyrosine phosphorylation.
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The purpose of this study was to determine if captopril, an angiotensin-converting enzyme inhibitor, could interact with iron ions and so modify a Fenton type reaction. Results indicate that different degrees of thiobarbituric acid-reactive substance from deoxyribose are obtained in an ascorbate-driven Fenton system depending on the order of addition of captopril and iron to the incubation medium. Similar results were obtained with the chelating reagents ethylenediaminetetraacetic acid and diethylenetriaminepentaacetic acid, indicating that the buffer solution plays a relevant role when a particular iron complex is formed with a chelating agent. These metal complexes produce oxidizing species in a Fenton type system whose nature is discussed.
The decrease of CD4+ cells in AIDS patients is widely documented, although the selective loss within different subsets of CD4+ cells and the mechanisms involved in this phenomenon are controversial. In the present report we have analyzed the proliferative response to Ag and mitogen of peripheral blood T lymphocytes from HIV-infected individuals, the phenotype profile of CD26+ and CD26- subset of cells and their infectivity by the HIV. The expression of CD26 Ag, either in CD4+ or CD8+ cells, was clearly diminished in all the patients tested. On the other hand, the expression of CD29 seems not to be affected, nevertheless T cells from these patients were unable to generate a proliferative response against soluble Ag. In 11 out of 13 patients, polymerase chain reaction studies demonstrated that the CD26- subset of CD4+ cells was the main reservoir for HIV-1 in infected individuals and HIV-1 virus preferentially infected in vitro CD4+/CD26- subpopulation. This capacity for preferential infectivity, together with the selective loss of cells expressing CD26 Ag, helps to explain the progressive impairment in the immune system of these patients and sheds new light on our understanding of the AIDS pathophysiology.
Interleukin (IL)-1 alpha activates multiple signal transmission pathways in the T helper type 2 cell line, D10A, and these pathways are linked to two separate IL-1 receptors (IL-1R). In the present report we show that IL-1 induces the activation of tyrosine kinase in these cells, leading to tyrosine phosphorylation of a subset of proteins of 38, 75, 97 and 115 kDa. This type of phosphorylation is prevented by a monoclonal antibody directed against the 80-kDa IL-1R and by tyrphostins which are specific inhibitors of tyrosine kinases. In addition, this inhibitor blocks IL-1-and IL-2-induced proliferation in D10A cells as well as the c-myc and c-myb proto-oncogene mRNA expression in response to IL-1. Interestingly, the inhibitor of cAMP-dependent kinase, H-8, only blocks IL-1-induced c-myb, but not c-myc mRNA expression. Altogether, our results demonstrate that the activation of a tyrosine kinase(s) is an early and major event that happens after IL-1/IL-1R interaction, leading to an increase in intracellular cAMP which results in c-myb and IL-5 mRNA expression. Independent of cAMP, by tyrosine phosphorylation of specific substrates IL-1 also induces c-myc and IL-6 mRNA expression and cellular proliferation.
Interleukin (IL)-1 induces proliferation and expression of several protooncogenes in the T helper 2 cell line D10A. We have analyzed the signal transmission pathways activated by IL-1 in these cells, leading to the expression of c-jun and c-fos. IL-1 induced c-jun gene transcription and mRNA expression by means of a pathway dependent on protein tyrosine kinase activity since tyrphostin, a specific inhibitor of tyrosine kinase, inhibited this induction. This mechanism of transmission signaling was independent of protein kinase C (PKC) and was linked to the 80-kDa IL-1 receptor (IL-1R). In addition, phorbol esters did not induce c-jun mRNA expression, whereas c-fos mRNA expression mediated by IL-1 dependent on PKC; this pathway was linked to a different, still unidentified IL-1R that was functional in the D10A cell line. Accumulation of intracellular cAMP generated by IL-1 through the 80-kDa IL-1R negatively regulated c-fos expression which was induced by IL-1 through PKC activation. We conclude that IL-1 modulates the expression of c-fos in D10A cells by occupying of two independent IL-1R that are linked to different signal transduction pathways.
Fine needle aspiration (FNA) of the salivary glands was carried out on 97 patients. Diagnosis was confirmed by histological findings in 93 patients. There were 75 benign lesions (including 52 benign tumours) and 18 malignant lesions. In our series "positive predictive value" of FNA was 0.900 and the negative predictive value was 0.963. Thus, the probability of a false positive is 0.100 and of a false negative 0.037.
Among the techniques currently used for the detection of human papillomavirus (HPV) in genital lesions, only two correlate HPV with the histopathological findings of the lesion: immunohistochemistry and in situ hybridization. Consequently, we were prompted to carry out a comparative study on both techniques to check their utility and efficacy as routine diagnostic methods. 52 biopsy specimens of uterine cervix diagnosed histopathologically as condylomas and cervical intraepithelial neoplasia+koilocytosis were studied by immunohistochemical and in situ hybridization techniques using a polyclonal antibody against the common antigen of the HPV capsid and three biotinylated DNA probes specific to HPV types 6/11, 16/18 and 31/35/51. Immunohistochemistry detected 21 positive cases (40.38%), whereas in situ hybridization detected 40 positive cases (76.92%); of the latter, 30 were positive for HPV types 6/11, 3 for HPV types 16/18 and 11 for HPV types 31/35/51. The results suggest that in situ hybridization is a more sensitive technique than immunohistochemistry. However, we recommend the use of both techniques in the case of potentially malignant lesions since better prognostic information can be obtained from joint analysis of both results.
CD26 antigen distribution among lymphoid cells and its participation in the process of lymphocyte activation and proliferation has been widely documented. However, the molecular and biochemical mechanisms coupled to the CD26 molecule are not yet known. With different monoclonal antibodies (mAb) we have detected that approximately 56% of CD4+ and 35% of CD8+ cells from peripheral blood lymphocytes express CD26 and the expression of this antigen is required for antigen- but not for mitogen-induced proliferation unless exogenous interleukin-2 (IL-2) is added to the culture. The stimulation of nylon wool-separated T cells and T-cell clones by the anti-CD26 mAb, 134-2C2, induced tyrosine phosphorylation on a subset of proteins of 50,000, 46,000, 26,000, 24,000 and 21,000 MW. This pattern of phosphorylation was not affected by the presence of 12-myristate 13-acetate (PMA), although this cofactor is required for CD26-mediated IL-2 mRNA expression and T-cell proliferation. When a specific tyrosine kinase inhibitor, Tyrphostin, was used in CD4+ cells cultures stimulated with 134-2C2 and PMA, the proliferation and the expression of IL-2 mRNA were inhibited. Thus, protein tyrosine phosphorylation seems to play a major role in CD26-mediated T-cell proliferation.
Diagnosis of human papillomavirus (HPV) infection in uterine cervical lesions is usually based on histopathological criteria and, in some cases, is confirmed by immunohistochemistry. The recent development of in situ hybridization techniques has facilitated the detection of HPV in these lesions. Consequently, we carried out a study on 18 uterine cervical biopsy specimens histopathologically diagnosed as severe dysplasias and carcinomas in situ, using an immunohistochemical method with a rabbit polyclonal antibody against the HPV common structural antigen and in situ hybridization techniques with three biotinylated DNA probes for HPV types 6/11, 16/18, and 31/35/51. By immunohistochemistry only one case (5.5%) proved to be positive, whereas by in situ hybridization 12 HPV-positive cases were obtained (66.6%), of which 7 were positive for HPV types 16/18 (38.8%) and 6 for HPV types 31/35/51 (33.3%). One case was positive with positive with both DNA probes. From our results it can be inferred that in situ hybridization is a more sensitive technique than immunohistochemistry for confirming the presence of HPV in severe dysplasias and carcinomas in situ of the uterine cervix. Furthermore, in situ hybridization provides much more information than immunohistochemistry since it permits the identification of the HPV types causing the lesion.
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Streptokinase is an extracellular protein produced by several strains of streptococci. It functions in the species-specific conversion of plasminogen to plasmin. In this paper we describe the purification of streptokinase by affinity chromatography on human plasminogen acylated with p'-nitrophenyl p-guanidinobenzoate. The acylated and non-acylated plasminogen and plasmin were coupled to cyanogen bromide-activated Sepharose 4B and evaluated for streptokinase purification. These results show that a homogeneous preparation of streptokinase with high specific activity and high yield can be obtained using acylated plasminogen. This method permits the binding of one milligram of streptokinase per milliliter of swollen gel.