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Biomedical subjects

N Marx

Publications and source records attributed to N Marx.

30 records · Page 2Linked to original sources

Induction of cytokine expression in leukocytes in acute myocardial infarction.

OBJECTIVES: This study sought to investigate whether cytokine expression in leukocytes may be induced by plasma from the reperfused heart of patients with an acute myocardial infarction (MI). BACKGROUND: Reperfusion in acute MI is associated with deleterious local and systemic inflammatory responses that are regulated by cytokines. Induction of cytokine expression in resident leukocytes could contribute to inflammatory responses of the ischemic and reperfused heart. METHODS: Blood samples of 10 patients with an acute MI were obtained simultaneously from the coronary sinus and the aorta before and 5 min after recanalization of the coronary occlusion. Ten patients with elective percutaneous transluminal coronary angioplasty served as a control group. We incubated leukocytes from healthy donors with plasma samples and analyzed mRNA expression of interleukin (IL)-1 beta, IL-6, IL-8 and tumor necrosis factor-alpha (TNF-alpha) by Northern blot analysis. RESULTS: In patients with an acute MI, plasma obtained from the coronary sinus after recanalization increased the mRNA expression of IL-1 beta and IL-8 compared with that of plasma before recanalization (median [quartiles] difference before vs. after recanalization: 34.5 [4, 137], p = 0.017, for IL-1 beta; 18.5 [4, 35], p = 0.032, for IL-8) and simultaneously obtained aortic plasma (median [quartiles] coronary sinus-aortic differences after recanalization: 45.5 [-3, 115], p = 0.021, for IL-1 beta; 16 [4, 52], p = 0.005, for IL-8). No induction of IL-6 and TNF-alpha expression could be observed. No changes found in the study patients were detectable in the control group. CONCLUSIONS: Plasma from the ischemic and reperfused heart stimulates the expression of IL-1 beta and IL-8 in leukocytes. Therefore, leukocyte-derived cytokines may contribute to the regulation of cardiac inflammatory responses in patients with an acute MI.

Adult↗

Diarrheal epidemics among Rwandan refugees in 1994. Management and outcome in a field hospital.

We describe the clinical course and outcome of Rwandan refugees with cholera-like illness (n = 567) and clinical dysentery (n = 1,062) treated at the Israeli Army field hospital in the disaster region of Goma, Zaire, during the summer of 1994. Vigorous fluid administration was the primary therapy, complemented with antibiotics for patients with presumed Shigella infection. Recovery rates were 94% and 96% for patients with cholera and dysentery, respectively. Mortality was substantially affected by comorbid conditions such as pneumonia and meningitis, which occurred in one-quarter of these patients. Infective, metabolic, and surgical complications (including three cases of intussusception) may have contributed to the deaths. The outcome of patients during diarrheal epidemics of cholera or bacillary dysentery may be favorable, even in disaster settings, if patients are evacuated promptly to medical facilities and appropriate therapy is instituted. We close with general observations on procedures to be followed in future epidemics of diarrheal diseases.

Adolescent↗

Effect of human recombinant interleukin-6 and interleukin-8 on monocyte procoagulant activity.

Interleukin (IL)-6 and IL-8 are important regulators of inflammatory responses in myocardial infarction. Induction of monocyte procoagulant activity (PCA) by these cytokines could present a mechanism that links inflammatory responses to thrombotic events. We therefore investigated the effect of IL-6 and IL-8 on monocyte tissue factor (TF) expression. Recombinant human IL-6 and IL-8 caused a time- and dose-dependent increase in PCA (recalcification time) of monocytic U937 cells and of mononuclear leukocytes. Using blocking anti-TF monoclonal antibodies and factor VII-deficient control plasma, this PCA was shown to be TF dependent. Compared with unstimulated cells, mononuclear cell PCA increased by 4.5-fold to 17 +/- 2 mU/5x10(5) cells after exposure to 100 ng/L IL-6 for 4 hours and by 6.6-fold to 27 +/- 4 mU/5x10(5) cells after exposure to IL-8 under the same conditions. Northern blot analysis showed an increase in TF mRNA after stimulation with IL-6 or IL-8 for 2 hours, and after 4 hours an increase in cellular TF protein content was found by immunoassay. Flow cytometry demonstrated that IL-6 and IL-8 induced an increase in TF surface expression on monocytes. Thus, IL-6 and IL-8 induce monocyte PCA by increasing mRNA, protein content, and surface expression of TF.

Blood Coagulation Factors↗

Risk of infection with Helicobacter pylori and hepatitis A virus in different groups of hospital workers.

OBJECTIVES: The purpose of this study was to determine whether different staff groups in an acute care hospital are at increased risk of acquiring Helicobacter pylori and hepatitis A virus infection. METHODS: We examined staff members of an acute care hospital for serum antibodies to H. pylori IgG (n = 457) and to hepatitis A virus (n = 434). The staff members were assigned to three groups: 1) nonmedical staff (n = 110), 2) medical and nursing staff (n = 272), and 3) medical and nursing staff working in a gastroenterology and endoscopy unit (n = 75). Serum antibodies were measured by validated enzyme immunoassays. A questionnaire inquiring about medical and professional history, history of upper GI pain and ulcer, as well as about the use of nonsteroidal anti-inflammatory drugs or medication for GI complaints and smoking habits was completed by each person. RESULTS: The seroprevalence of H. pylori was 35.5% in group I, 34.6% in group II, and 24.0% in group III (not significant). The seroprevalence of H. pylori antibodies increased with age (p < 0.001), and antibodies were present more frequently in women than in men (36.2 vs 25.4%, p < 0.05). After adjustment for age, duration of experience and the number of years working in the gastroenterology or endoscopy unit did not increase H. pylori seropositivity. No significant association was found between H. pylori seropositivity and history of upper GI pain, ulcers, use of nonsteroidal anti-inflammatory drugs or medication for GI complaints, or tobacco use. The prevalence of hepatitis A antibodies was similar in the three groups (group I, 26.4%; II, 26.5% III, 21.7%; not significant). Cross-tabulation showed that 67 subjects (15.4%) were seropositive for both H. pylori and hepatitis A (p < 0.001) and that 245 (56.5%) were negative for both. Seventy-seven (17.7.%) and 45 (10.4%) were seropositive for only H. pylori and for only hepatitis A, respectively. CONCLUSION: Occupational exposure to patients in an acute care hospital as well as to patients and to endoscopic procedures of a gastroenterology and endoscopy unit does not increase the rate of infection with H. pylori. The significant correlation between the seroprevalences of H. pylori and hepatitis A antibodies suggests fecal-oral transmission of H. pylori.

Adolescent↗

Functional intactness of stimulatory and inhibitory autocrine loops in human renal carcinoma cell lines of the clear cell type.

PURPOSE: The aim of the present study was to analyze the contribution of different stimulatory and inhibitory growth factors to the deregulated proliferation of human RCCs. MATERIALS AND METHODS: The expression of different growth factors and their corresponding receptors were analyzed by Northern blot, FACS, ELISA and immunocytochemistry in 13 permanent human RCC cell lines of the clear cell type. Moreover, the functional intactness of growth factor-related signal transduction pathways was investigated. RESULTS: All RCC cell lines expressed EGF-receptor mRNA and protein and 10 cell lines secreted TGF-alpha. Exogeneously added TGF-alpha resulted in a significant (p < 0.05) stimulation of growth in 6 RCC cell lines and a significant (p < 0.05) inhibition of proliferation in 3 cell lines. PDGF B and the corresponding type beta receptor were expressed in a single cell line. mRNA expression of PDGF A and PDGF-alpha-receptor as well as IGF-1 and its receptor could not be detected in any cell line. Eleven RCC cell lines expressed TGF-beta 1 mRNA and in all cell lines TGF-beta 1 secretion into the supernatant could be demonstrated. Whereas all cell lines exhibited TGF-beta type II-receptor mRNA, type I-receptor mRNA could be detected only in 3 cell lines. TGF-beta type III-receptor was observed in 1 cell line. Exogeneously added TGF-beta1 resulted in a significant (p < 0.05) inhibition of proliferation in 7 RCC cell lines. CONCLUSION: Clear cell RCCs exhibit a complex and heterogeneous expression pattern for various growth factors and their receptors. Growth factor secretion and intact signal transduction pathways in most clear cell RCCs facilitate an intricate modulation of RCC growth by autocrine and paracrine interactions between tumor cells and host tissue.

Carcinoma, Renal Cell↗

Cytomorphological, cytogenetic, and molecular biological characterization of four new human renal carcinoma cell lines of the clear cell type.

Four new permanent cell lines (RCC-A, -B, -C, and -D) derived from different human renal cell carcinomas of the clear cell type were established in tissue culture. The cell lines displayed characteristic differences in cell size and shape, which allowed individual identification by phase contrast microscopy. Ultrastructurally, the cell lines exhibited varying amounts of cytoplasmatic glycogen and lipid. Immunohistochemistry revealed co-expression of vimentin and cytokeratin in all cell lines. The mean population doubling time ranged from 27 h (RCC-A) to 104 h (RCC-D). RCC-B and -C cells produced slowly growing tumours after heterotransplantation into nude mice, whereas RCC-A and RCC-D cells were non-tumorigenic. The modal chromosome number was either near-diploid (RCC-A, -B, and -C) or near triploid (RCC-D). Clonal abnormalities affecting the short arm of chromosome 3 were seen in all cell lines. Northern blot analysis revealed no expression of the proto-oncogenes c-fos, c-ros, and c-mos, whereas c-Ki-ras expression was observed in all cell lines. Expression of c-myc was observed in RCC-A, RCC-B, and RCC-D cells, whereas c-raf expression could be detected in RCC-B and RCC-D. Tumour suppressor gene p53 mRNA was observed in the cell line RCC-D.

Adenocarcinoma, Clear Cell↗

Meningococcal meningitis among Rwandan refugees: diagnosis, management, and outcome in a field hospital.

OBJECTIVE: To study the diagnostic process, clinical course, and outcome of Rwandan refugees with meningococcal meningitis, treated in an Israeli field hospital in Goma, Zaire, in the summer of 1994. METHODS: Patient hospital charts and laboratory records were reviewed with critical evaluation of clinical presentation and diagnostic tests. Patients were treated as part of a disaster relief effort in a refugee camp experiencing several coexisting lethal epidemics. RESULTS: A total of 65 patients were identified as having group A meningococcal meningitis. Latex agglutination test for Neisseria meningitidis soluble antigen in the cerebrospinal fluid was found to be a superior diagnostic tool, as compared to Gram stain, and at least as effective as culture. The mortality rate was 14%; mortality was markedly affected by co-morbidity (e.g., dysentery, pneumonia, and malnutrition). CONCLUSIONS: The outcome of patients with meningococcal meningitis, treated in referral centers within a disaster area may be favorable, despite overwhelming coexisting epidemics, and may be comparable to that achieved in advanced medical facilities. Encephalopathy may be a diagnostic pitfall in the perspective of coexisting epidemics, requiring a high index of suspicion and routine lumbar puncture. The latex agglutination test is highly useful in achieving prompt diagnosis of meningococcal meningitis, in particular when sample handling for culture and microscopy is suboptimal.

Adolescent↗

[Arterial tortuosity syndrome].

The arterial tortuosity syndrome is a rare congenital disorder characterized by elongation and generalized tortuosity of the major arteries including the aorta. Associated clinical features consist of excessively stretchable skin and joint laxity which is indicative of a connective tissue disorder such as Ehlers-Danlos or Cutis laxa syndrome. The gene locus of the arterial tortuosity syndrome has recently been localised on chromosome 20q13; inheritance ist autosomal recessive. - We report on a newborn with arterial tortuosity syndrome and hiatal hernia, bilateral hip dislocation, inguinal hernias and diffuse tortuosity of the great arteries including the aorta. Known gene loci involved in Ehlers-Danlos syndrome, cutis laxa syndrome and other connective tissue disorders were excluded by specific DNA markers. By homozygosity mapping with polymorphic microsatellite markers it was possible to confirm the gene locus for the ATS on chromosome 20q13. In addition to the presentation of this patient, a review of the literature is presented.

Abnormalities, Multiple↗

Differentiation induction in the human rhabdomyosarcoma cell line TE-671. A morphological, biochemical and molecular analysis.

In the clonal human rhabdomyosarcoma cell line TE-671-1A, the expression of genes implicated in myogenic differentiation was determined before and after exposure to the differentiation inducers retinoic acid (RA), sodium butyrate (NaBut) and N-monomethylformamide (NMF). Exposure to NaBut or RA resulted in a significant (NaBut: p < 0.0001; RA: p < 0.05) increase in biochemical differentiation paralleled by a significant (NaBut: p < 0.0001; RA: p < 0.0002) inhibition of proliferation. An increase in the relative number of myotube-like giant cells was observed after exposure to NaBut. Exposure to NMF proved to be least effective and produced a significant (p < 0.0001) inhibition of proliferation without increase in differentiation. On the molecular level, exposure to RA resulted in a moderate increase in RAR a mRNA expression, whereas CRABP mRNA remained constant. RAR beta and RAR gamma mRNA were not expressed. mRNA expression of c-raf, c-myc and c-Ki-ras remained constant before and after exposure to all inducers of differentiation. C-fos mRNA was not expressed. In summary, differentiation can successfully be induced in the human rhabdomyosarcoma cell line TE-671-1A by various inducers of differentiation. In contrast to other myogenic cell lines, however, the proto-oncogenes myc, fos and raf are not involved in the transmission of myogenic differentiation signals in TE-671-1A cells.

Antineoplastic Agents↗

Effects of TNF-alpha and retinoic acid on the proliferation of the clear cell and chromophilic types of human renal cell carcinoma in vitro.

Since no effective therapeutic approach is known so far for metastatic renal cell carcinoma (RCC), we analyzed the anti-proliferative effects of TNF-alpha and retinoic acid (RA), applied either alone or in combination on 7 different RCC cell lines in vitro. In 5 out of 7 cell lines, a significant (p < 0.05) dose-dependent inhibition of tumor cell proliferation became evident after exposure to TNF-alpha, the response being of modest magnitude in 5 cell lines. In 2 cell lines the effects were more pronounced with a reduction of cell viability to 55 +/- 11% of the control. Northern blot analysis revealed no expression of TNF-alpha and p75 TNF-receptor in any cell line. All the cell lines showed p55 TNF-receptor mRNA. Scatchard analysis revealed no correlation between TNF-alpha receptor status and growth inhibitory response to TNF-alpha, the number of TNF-receptors per cell ranging from 0 to 3,976, and the affinity values from Kd = 0.621 nmol/l to Kd = 4.28 nmol/l. Exposure to RA alone resulted in significant (p < 0.05), but modest growth inhibition in 2 out of 7 cell lines with a reduction of cell viability to 83 +/- 1% of the control. In 2 out of 7 cell lines, combination of RA and TNF-alpha was significantly (p < 0.05) more effective than the single application of each compound. Northern blot analysis revealed no transcripts of CRABP I and retinoic acid receptor (RAR)-beta. All the cell lines expressed RAR-alpha mRNA and one cell line additionally expressed RAR-gamma mRNA. A correlation between RAR status and RA response was not seen.

Adenocarcinoma, Clear Cell↗