[Adjuvants in desensitization solutions].
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Aluminum Hydroxide↗
Biomedical subjects
C Müller
Publications and source records attributed to C Müller.
Ondansetron for pruritus due to cholestasis.
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Cholestasis↗
Influence of sex, age, body mass index, and smoking on alcohol intake and mortality.
OBJECTIVE: To examine the association between self reported alcohol intake and subsequent mortality from all causes and if the effect of alcohol intake on the risk of death is modified by sex, age, body mass index, and smoking. DESIGN: Prospective population study with baseline assessment of alcohol and tobacco consumption and body mass index, and 10-12 years' follow up of mortality. SETTING: Copenhagen city heart study, Denmark. SUBJECTS: 7234 women and 6051 men aged 30-79 years. MAIN OUTCOME MEASURE: Number and time of deaths from 1976 to 1988. RESULTS: A total of 2229 people died, 1398 being men. A U shaped curve described the relation between alcohol intake and mortality. The lowest risk was observed at one to six alcoholic beverages a week (relative risk set at 1). Abstainers had a relative risk of 1.37 (95% confidence interval 1.20 to 1.56) whereas those drinking more than 70 beverages a week had a relative risk of 2.29 (1.75 to 3.00). Among the drinkers, the risk was significantly increased only among those drinking more than 42 beverages a week. Sex, age, body mass index, and smoking did not significantly modify the risk function. The risk among heavy drinkers was slightly reduced when smoking was controlled for. The risk function was similar in the first and second period of six years of observation. CONCLUSION: Alcohol intake showed a U shaped relation to mortality with the nadir at one to six beverages a week. The risk function was not modified by sex, age, body mass index, or smoking and remained stable over 12 years.
Adult↗
Regulation of RAG-1 and CD69 expression in the thymus during positive and negative selection.
Successful interaction of the T cell receptor (TCR) with major histocompatibility complex (MHC) molecules during thymic selection down-regulates the expression of the recombination activating genes (RAG)-1 and -2 in cortical thymocytes and thereby prevents further endogenous TCR alpha-chain gene rearrangements (Borgulya, P., Kishi, H., Uematsu, Y. and von Boehmer, H., Cell. 1992. 69: 529-537; Brändle, D., Müller, C., Rülicke, T., Hengartner, H. and Pircher, H., Proc. Natl. Acad. Sci. USA 1992. 89: 9529-9533). To address the question whether down-regulation of RAG-1 activity represents an irreversible process we have blocked TCR-MHC interactions of thymocytes with thymic stromal cells. Firstly, transgenic (Tg) mice expressing a virus-specific MHC class I (H-2Db)-restricted TCR were injected with anti-Db or anti-CD8 monoclonal antibodies and RAG-1 expression was examined by in situ hybridization on thymus sections. The results show that cortical thymocytes up-regulated RAG-1 expression within 24 h after antibody administration. Secondly, immature thymocytes from TCR Tg mice were released from the thymic microenvironment and cultured in vitro for 14 h in single-cell suspension. The amount of RAG-1 mRNA was increased sixfold in cultured cells when compared to freshly isolated thymocytes. In addition, we show that immature thymocytes from TCR transgenic mice bearing non-selective MHC molecules (H-2d) down-regulated RAG-1 expression after antigen-induced TCR engagement. Cytofluorometric analysis further revealed that surface expression of CD69 on immature thymocytes inversely correlated with RAG-1 expression during positive and negative selection processes.
Animals↗
Epitope mapping and functional studies with three monoclonal antibodies to the c-kit receptor tyrosine kinase, YB5.B8, 17F11, and SR-1.
Three monoclonal antibodies (MAbs) to the human c-kit receptor tyrosine kinase (P145c-kit), derived in independent laboratories, have been extensively used in studies of c-kit expression and the role of its ligand, steel factor (SLF), in hemopoiesis and mast cell differentiation and function. In this study, the relationship between the epitopes they identify, and their effects on SLF binding, receptor internalization, and signal transduction are compared. Epitope mapping studies carried out on the high P145c-kit-expressing cell line HEL-DR showed that SR-1 identifies an epitope independent of those bound by YB5.B8 and 17F11, while the latter two antibodies bound to distinct but interacting epitopes. SR-1 potently blocked the binding of SLF to P145c-kit on these cells and also on cells of the factor-dependent line MO7e. In contrast, YB5.B8 and 17F11 had minimal effects on ligand binding. Conversely, SLF partially blocked the binding of SR-1 and YB5.B8 to cells, while binding of 17F11 was actually enhanced by SLf on some target cells. Preincubation of HEL-DR and MO7e cells with MAbs prior to exposure to SLF revealed that 17F11 itself brought about partial down-regulation of P145c-kit and did not inhibit SLF-mediated down-regulation. SR-1 caused minimal down-regulation and inhibited SLF-mediated receptor internalization. YB5.B8 had minimal effects on either cell line in this assay. To determine whether the antibodies had any agonist activity, they were compared with SLF for their ability to bring about receptor phosphorylation in intact MO7e cells. All three antibodies induced detectable tyrosine phosphorylation with 17F11 being the most effective, while YB5.B8 was the least effective. Finally, the ability of the antibodies to influence the proliferation of the MO7e cells was examined. As expected, SR-1 potently inhibited the proliferative response to SLF, while 17F11 weakly inhibited and YB5.B8 had negligible effect. In the absence of SLF both 17F11 and YB5.B8 displayed very weak but reproducible agonist activity.
Animals↗
T lymphocytes, CD68-positive cells and vascularisation in thyroid carcinomas.
Immunohistochemical detection and quantification of CD3- and CD45RO-positive lymphocytes and CD68-positive cells in 75 thyroid carcinomas of follicular cell origin revealed rising levels for these parameters associated with dedifferentiation. A parallel trend towards reduction of vascularisation, determined as CD31-positive blood vessels, with decreasing differentiation became evident, statistically only significant when well-differentiated follicular and anaplastic carcinomas were compared. Positive correlations could be demonstrated between the density of CD68-, CD3-, and CD45RO-positive cells as well as between the density of CD68-, and CD3-, and CD45RO-positive cells and vascularisation. These correlations were expected, as the interaction of CD68-positive cells and T lymphocytes results in the production of angiogenesis factors, ultimately leading to better vascularisation of the tumour. Nevertheless, the tumour cells themselves are variously capable of producing angiogenic substances. The obvious lack of positive correlation between the density of tumour-infiltrating cells determined in this study and vascularisation, despite reduced vascularisation in less differentiated tumours that contained increasing numbers of tumour-infiltrating cells, seems to be due to functional heterogeneity of morphologically similar tumours.
Antibodies, Monoclonal↗
Initiation of visual-guided random saccades and remembered saccades in parkinsonian patients with severe motor-fluctuations.
We studied the initiation of saccades to visual-guided random time and remembered targets in a group of nine Parkinsonian patients with severe motor fluctuations and in 9 age matched control subjects. In contrast to a marked skeletomotor improvement during the "on" condition, saccadic latencies for both visual-guided random saccades and remembered saccades were increased in the patients during the "on" condition compared to the "off" condition. This result of dissociation between skeletomotor and oculomotor function indicates that common concepts of saccadic initiation in parkinsonian patients do not hold true in patients with severe fluctuations since dopaminergic stimulation seems to increase saccadic latencies in these patients.
Aged↗
[The relevance of CDT (carbohydrate-deficient transferrin). Preoperative diagnosis of chronic alcohol abuse in intensive care patients following elective tumor resection].
The increase of alcoholism-related problems is associated with vital postoperative clinical complications in chronic alcohol abusers. In particular, the alcohol withdrawal syndrome (AWS) may provoke potentially life-threatening complications in alcohol-dependent patients. Hence, a precise diagnosis of alcohol dependence is mandatory preoperatively, requiring an extensive case history using alcoholism-associated questionnaires. Additional new biological markers for detecting alcoholism could improve the accuracy of preoperative diagnosis. Carbohydrate-deficient transferrin (CDT) reflects increased alcohol consumption. The aim of our interdisciplinary study was to investigate whether the validity of the preoperative diagnosis of chronic alcohol abuse might be improved by measuring CDT. METHODS. A total of 45 patients from the departments of Otorhinolaryngology, Maxillofacial Surgery, and Abdominal and Thoracic Surgery were included in our prospective clinical study. Patients underwent resection of malignant oral, pharyngeal, laryngeal, or oesophageal tumours and were transferred to the intensive care unit for postoperative management. Routine preoperative history, examinations, and laboratory tests including GGT, MCV, ASAT, and ALAT, were supplemented by a specific alcohol-related questionnaire and CDT measurement. The patients were categorised in four groups based on history and the questionnaire: continuously abstinent subjects; sober subjects for at least 7 days; chronic abusers; and dependent subjects. CDT was separated by isocratic anion exchange chromatography and quantified by turbidimetric determination. Statistical analysis was performed by the Kruskal-Wallis test. RESULTS. Preoperatively, 21 patients were at major risk for alcoholism-related complications: 12 were chronic abusers and 9 were diagnosed as dependent. CDT was significantly increased in both groups, and was pathologically elevated in 16 of the 21 patients. Sampling occurred significantly long after the last alcohol intake in the 5 patients with normal CDT values (median: 6.0 days; range: 2-12 days) compared with the 16 with pathologically elevated CDT levels (median: 1.0 day; range: 0-4 days; P = 0.002). The sensitivity of CDT elevation was 16 out of 24 (76%), the specificity 16 out of 16 (100%). Sixteen patients had no previous history of alcohol consumption (sober for at least 7 days) and 8 were definitely abstinent. Both of these groups had normal CDT values. CONCLUSIONS. CDT was a sensitive and specific marker for chronic alcohol consumption in our patient population. Since CDT is a state marker, repeated determinations might be useful to estimate a patient's drinking habits. The combination of CDT and an alcohol-related questionnaire was reliable for detecting alcohol-dependent patients preoperatively.
Adult↗
Isolation and characterization of Textarin, a prothrombin activator from eastern brown snake (Pseudonaja textilis) venom.
The venom of P. textilis contains two different enzymes which convert human prothrombin into thrombin. Prothrombin activation by Textarin, a serine proteinase containing a calcium-binding molecule site, with a molecular mass of 50,000 to 53,000 Da and I.P. 5.5, separated from crude venom by either barium citrate adsorption or hydroxyl apatite chromatography, is strongly stimulated by phospholipid and calcium ions. A second activator, found in the supernatant of barium citrate adsorbed venom solution, activates prothrombin in the absence of any co-factor. Human plasma coagulation induced by Textarin, phospholipid and calcium ions is affected by lupus anticoagulants. Textarin may thus be used for the detection of lupus anticoagulants in patient plasma samples.
Amino Acid Sequence↗
Antibodies against CD4+ lymphocytes in plasma of HIV-infected patients are related to CD4 cell depletion in vivo.
The role of autoimmune phenomena in the pathogenesis of AIDS is not well understood. Antibodies against CD4+ lymphocytes are frequently detectable in HIV-infected patients. However, the relevance of these antibodies is unknown. In this study anti-CD4 cell antibodies in plasma of HIV-infected patients were compared to patients' CD4 cell count. Lymphocytes of a healthy donor were incubated with plasma of patients and controls. Antibodies against CD4+ lymphocytes were detected using anti-human Ig antibodies and monoclonal anti-CD4 antibodies simultaneously. The degree of staining was visualized by flow cytometry. The experiments revealed that 60% of HIV-infected patients harbored anti-CD4 cell antibodies in their plasma. Anti-CD4 cell antibodies were not detectable in plasma of healthy controls. Patients with anti-CD4 cell antibodies in their plasma presented with significantly lower numbers of circulating CD4+ lymphocytes (P = 0.025). The degree of antibody reactivity was negatively correlated to patients' CD4 cell counts (P = 0.02). In conclusion there is evidence for an association between plasma anti-CD4 cell antibodies and CD4 cell depletion. Whether this association represents an epiphenomenon or a pathogenetic relevant pathway needs to be investigated in further studies.
Antilymphocyte Serum↗
Sensors as components of integrated analytical systems.
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Biosensing Techniques↗
Soluble CD8 and soluble CD4 antigens in viral hepatitis and alcoholic cirrhosis.
Serum levels and production of soluble CD8 and soluble CD4 antigens by peripheral blood mononuclear cells were determined in patients with alcoholic cirrhosis and acute or chronic viral hepatitis. Patients with chronic viral hepatitis had significantly increased soluble CD8 serum levels (n = 18; 734 +/- 143 U/ml) (mean +/- SD) compared to healthy controls (n = 80; 312 +/- 141 U/ml; p < 0.001) and patients with alcoholic cirrhosis (n = 12; 505 +/- 256 U/ml; p = 0.006), whose soluble CD8 concentrations were also higher than controls (p < 0.001). In contrast, soluble CD4 antigen serum levels were similar in all groups. In addition, patients with chronic hepatitis showed an increased production of soluble CD8, but not soluble CD4, after mitogenic stimulation of their peripheral blood mononuclear cells compared to controls or patients with alcoholic cirrhosis. Patients with acute viral hepatitis, studied within the first 2 weeks after onset of jaundice, showed markedly elevated serum concentrations of soluble CD8 (n = 4; 807 +/- 379 U/ml; p < 0.001 vs. controls), but not soluble CD4. In addition, nine patients with chronic hepatitis C were studied during and after treatment with alpha interferon. Soluble CD8 serum concentrations of six treatment responders were not found to be different from the low levels seen in controls, whereas three non-responders had increased soluble CD8 levels which were similar to levels in untreated patients with chronic hepatitis C. After interferon-alpha therapy ended, a significant elevation of soluble CD8 serum concentrations was observed in four relapsing patients, which paralleled the serum ALT increase.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
The effect of methylene blue phototreatment on plasma proteins and in vitro coagulation capability of single-donor fresh-frozen plasma.
BACKGROUND: Photodynamic virus inactivation of fresh-frozen plasma (FFP) may result in its impaired coagulation capability. STUDY DESIGN AND METHODS: Double-volume plasmapheresis samples from 11 donors were divided in pairs of 250 mL. One group underwent methylene blue (MB) phototreatment (MB-FFP). The other group was treated according to the standards of the American Association of Blood Banks for preparation and storage of FFP. Parameters of hemostasis and clinically important plasma proteins were tested in native plasma, thawed MB-FFP, thawed FFP, and twice-frozen and thawed FFP (FFP-II). RESULTS: Mean activities of factor V (73.4 vs. 94.5%; p < 0.01), factor VIII (58.1 vs. 86.7%; p < 0.001), and fibrinogen (1.8 vs. 2.8 g/L; p < 0.001) were reduced in MB-FFP as compared to those in FFP. The comparison of MB-FFP to FFP-II revealed reduced activities of factor VIII (58.1 vs. 85.2%; p < 0.001) and fibrinogen (1.8 vs. 2.8 g/L; p < 0.001) but no changes in factor V. Activated partial thromboplastin time in MB-FFP was prolonged beyond the upper normal range (+5.3 sec; p < 0.001) and prothrombin time increased in MB-FFP versus FFP (+0.96 sec; p < 0.001). CONCLUSION: MB phototreatment reduces the in vitro coagulation capacity of FFP, most likely as a result of the effects of an additional freezing and thawing procedure and photooxidation-induced protein damage.
Blood Coagulation↗
[Tuberculous meningoencephalitis in post-embryo transfer status].
A 30-year old pregnant woman, who received an embryo transfer, suffered since the 12th week of pregnancy from therapy-resistant attacks of fever for several weeks. With progressive deterioration, the increasingly somnolent patient showed by now clear signs of meningism and acid-fast bacilli were found in the cerebrospinal fluid. NMR showed a finding consistent with bacterial meningoencephalitis. During therapy with INH, Rifa and EMB, the clinical course and the CSF findings showed rapid improvement. Nevertheless, spontaneous abortion occurred in the 23rd week of pregnancy. Previous history revealed, that granulomatous salpingitis had been diagnosed several years earlier as the reason for infertility.
Adult↗
Anti-lymphocyte antibodies in plasma of HIV-1-infected patients preferentially react with MHC class II-negative T cells and are linked to antibodies against gp41.
It has previously been shown that HIV-infected patients develop anti-lymphocyte antibodies. The relationship between anti-lymphocyte antibodies and antibodies against different viral antigens is unknown, and it remains controversial whether some lymphocyte subpopulations are targeted preferentially. We have set out using three-colour flow cytometry to measure antibodies against different lymphocyte subsets. Staining with anti-human immunoglobulin and two MoAbs was performed to characterize the immunoglobulin load of different lymphocyte subsets. Comparison was done between patients' antibody reactivity against HIV-1 antigens and anti-lymphocyte antibodies. We were able to demonstrate the presence of anti-lymphocyte antibodies in approximately 75% of the HIV-infected patients (n = 78) (healthy controls were all negative). MHC class II-negative T cells showed a stronger reaction with anti-lymphocyte antibodies than B cells or MHC class II-positive T cells. Patients with antibodies against CD4 lymphocytes showed a significantly higher antibody reaction with the retroviral antigen gp41 than patients without these antibodies. An association between anti-lymphocyte antibodies and antibody reactivity against other HIV-1 antigens was not noticed. In conclusion, anti-lymphocyte antibodies in HIV-1-infected patients show a preferential reactivity with T cells which lack expression of MHC class II molecules. There is an increased antibody reactivity against gp41 in patients with anti-CD4+ T cell antibodies. The association hints at a specific origin of anti-lymphocyte antibodies in HIV-1-infected patients due to cross-reactivity with viral epitopes or network phenomena. These anti-CD4 cell antibodies could be of interest in the clinical course of HIV infection.
Antigen-Antibody Reactions↗
Autoantibodies against ganglioside GM3 represent a portion of anti-lymphocyte antibodies in AIDS patients.
In this study we analysed the relationship between anti-lymphocytic ganglioside antibodies and anti-lymphocyte antibodies in AIDS patients. Anti-lymphocytic ganglioside antibodies were detected by thin layer chromatography (TLC) immunostaining; three colour flow cytometry was used to analyse circulating antibodies against different lymphocyte subsets. Anti-lymphocytic ganglioside antibodies were detected in 23 out of 49 AIDS patients sera (46.9%). All positive sera reacted selectively with the GM3 comigrating band from AIDS lymphocytes. Twenty two out of the 23 anti-lymphocytic GM3 positive sera also had antibodies against CD4+T cells, versus 17/26 anti-GM3 negative. Furthermore, patients with lymphocytic GM3 antibodies showed a significantly higher antibody reactivity against CD4+ T cells than patients in which these antibodies were not detected. The absorption tests revealed that preincubation of positive sera with GM3 was followed by a decrease in the reaction with target lymphocytes. These findings suggest that anti-GM3 antibodies are a portion, but not the majority, of antibodies reacting with CD4+ T cells.
Acquired Immunodeficiency Syndrome↗
Urinary excretion of thromboxane and markers for renal injury in patients undergoing cardiopulmonary bypass.
Urinary excretion of selected markers for renal injury, as well as urinary excretion rates of the thromboxane metabolite, 11-keto-thromboxane B2 (11k-TXB2), was studied in 36 male patients undergoing coronary bypass surgery using cardiopulmonary bypass (CPB). In all patients, excretion of both tubular (N-acetyl-beta-D-glucosaminidase [beta NAG]; alpha 1-microglobulin [alpha 1-MG]) and glomerular markers (albumin [Alb]; transferrin [Trf]; immunoglobulin G [IgG]) sharply increased on Day 1 after CPB, and they remained elevated throughout the observation period of 5 days. Urinary excretion rates of 11k-TXB2 markedly increased on Day 1 after surgery, and they rapidly decreased thereafter. In 12 of the 36 patients, a temporary increase of serum creatinine levels (> 1.30 mg/dl) was noted following surgery. A positive correlation was found between serum creatinine levels and excretion of the tubular enzyme beta NAG (r = 0.36; p < 0.05), but not between creatinine levels and alpha 1-MG or the glomerular markers. Furthermore, no correlation between urinary excretion of 11k-TXB2 and any of the urinary markers for renal injury could be detected. Our data do not strengthen the hypothesis that acute renal injury observed during CPB is related to exaggerated thromboxane biosynthesis in these patients. Monitoring of urinary markers for incipient renal damage, particularly excretion of beta NAG, might be of additional diagnostic value for detection of otherwise subclinical renal injury in patients undergoing CPB.
Acetylglucosaminidase↗
Contact allergy to a synthetic tannin in Tannosynt liquid.
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Adult↗