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Biomedical subjects

M Roos

Publications and source records attributed to M Roos.

At least 19 recordsLinked to original sources
PubMed1997

Efficacy and safety of a low-molecular-weight heparin and standard unfractionated heparin for prophylaxis of postoperative venous thromboembolism: European multicenter trial.

A randomized, double-blind multicenter trial was performed to compare the safety and efficacy of a new low-molecular-weight heparin (LMWH) (LU 47311, Clivarine) and standard unfractionated heparin for the prophylaxis of postoperative venous thromboembolism. Altogether 1351 patients scheduled to undergo abdominal surgery were included. Main outcome measures included the incidence of thromboembolic events (deep vein thrombosis, pulmonary embolism, or both) and bleeding complications, including wound hematoma. A total of 655 patients received 1750 anti-Xa IU of LMWH plus a placebo injection daily; 677 patients received 5000 IU of unfractionated heparin (UFH) twice a day. Both drugs were found to be equally effective, as 4.7% of patients in the LMWH group and 4.3% in the UFH group developed postoperative thromboembolic complications. However, the incidence of bleeding complications was significantly reduced in the LMWH group: 55 (8.3%) patients in the LMWH group and 80 (11.8%) in the UFH group developed bleeding complications, a relative risk (RR) of 0.70 (95% CI 0.51-0.97;p = 0.03); wound hematoma occurred in 29 (4.4%) of the LMWH group compared with 55 (7.7%) in those in the UFH group for an RR of 0.57 (95% CI 0.37-0.88;p = 0.01). This study confirmed that a very low dose of 1750 anti-Xa IU daily of this new LMWH is as effective as 10,000 IU of UFH for preventing postoperative deep vein thrombosis. At this dose its administration is associated with a significant reduction in the risk of bleeding including wound hematoma.

Adult↗
PubMed1996

Methodology for the establishment of growth standards.

Providing reference values in the form of percentiles for the assessment of paediatric growth is of great practical importance. Extreme centiles are particularly important in the diagnostic process. On the other hand, their statistical variability is inherently large. When measurements approximate to a normal distribution-as for height-centiles can be obtained more accurately. Otherwise, empirical centiles and/or more refined methods are needed. To exploit the age-dependent nature of centiles, smoothing methods are recommended. Accounting for midparental height as a covariate in the calculation of centiles greatly improves their validity due to an increased sensitivity and specificity.

Adolescent↗
PubMed1995

Ocular lens gap junctions: protein expression, assembly, and structure-function analysis.

Recent advances in understanding lens fiber gap junction formation are reviewed. These include studies of junctional protein expression in the embryonic lens, and of age related changes affecting gap junction structure and composition in the adult lens. An in vitro assembly system based on detergent solubilized pore complexes and endogenous lipids has been developed to provide information on the molecular interactions involved in gap junction formation and to provide material for structure analysis. Important information on the electrical properties of lens gap junction channels is obtained using electrophysiological techniques including planar lipid bilayer analysis and patch clamping.

Animals↗
PubMed1995

Culture of tumour-infiltrating lymphocytes from melanoma and colon carcinoma: removal of tumour cells does not affect tumour-specificity.

The therapeutic potential of adoptive therapy using tumour-infiltrating lymphocytes (TIL) has been demonstrated in a number of clinical trials. However, freshly isolated tumour-infiltrating lymphocytes (TIL) are often impaired in their proliferative and cytotoxic responses, which limits their use in immunotherapy. Several hypotheses with regard to the poor effector function of TIL have been postulated, including the production of immunosuppressive factors by tumour cells. In a previous paper we reported the efficient expansion of immunoreactive TIL from a variety of solid tumours by stimulation with a combination of monoclonal antibodies (mAbs) against CD3 and CD28. In the present study we analysed whether this protocol would be improved by the removal of tumour cells at the start of the culture. We tested a highly immunogenic tumour, melanoma, and a poorly immunogenic tumour, colon carcinoma. Removal of tumour cells highly improved anti-CD3/CD28 stimulated expansion of TIL from colon carcinoma, resulting in a significantly higher percentage of potentially tumour-specific CD8-positive T-cells and a reduced CD4/CD8 ratio compared to expansion in the presence of tumour cells. In contrast, expansion and CD4/CD8 ratio of melanoma-derived TIL was not significantly influenced by the removal of autologous tumour cells. CD3/CD28-stimulated melanoma TIL cultured in the absence of tumour cells showed specific lysis of autologous tumour cells comparable to melanoma TIL cultured in high-dose IL2. However, no cytotoxicity could be detected in colon TIL irrespective of the culture conditions used. On the other hand, 3/8 colon carcinoma TIL cultures and 9/12 melanoma-derived TIL cultures showed IFN gamma secretion upon stimulation with autologous tumour cells. We conclude that stimulation of TIL with a combination of mAbs to CD3 and CD28 in the absence of tumour cells induces efficient expansion of potentially tumour-specific cells from a highly and a poorly immunogenic tumour. Removal of tumour cells does not have a negative influence on the generation of tumour-specific T cells, while cell yield improves. Therefore, for large-scale cultures this protocol can efficiently induce the outgrowth of tumour-specific TIL, at the same time providing a useful source of autologous tumour cells that can be stored and used to direct or test antitumour specificity.

Antibodies, Monoclonal↗
PubMed1995

Ionization chamber dosimetry of proton beams using cylindrical and plane parallel chambers. Nw versus Nk ion chamber calibrations.

Determinations of the absorbed dose in a 170 MeV proton beam have been performed using seven ionization chambers of different types: five cylindrical (two FWT IC-18 and three NE-2571, of which one was modified to have the central electrode made of graphite) and two plane parallel (NACP-02 and Roos FK-6). The ionization was converted into absorbed dose in the proton beam according to the generalization of the formalism provided by the IAEA Code of Practice (TRS 277), which enables the use of the same equations for all kinds of beam used in radiotherapy. The absorbed dose obtained with the two IC-18 chambers, a chamber type commonly used as a reference in proton beams, was up to 1.5% lower than that obtained with the Farmer NE-2571 chamber, which was used as the reference in this work when calibration factors in terms of NK were used. To investigate this difference, experimental ND factors for six chambers (the two IC-18 chambers, the NACP-02, the FK-6 and two of the NE-2571 chambers) were determined in a high-energy electron beam. The procedure commonly recommended for plane parallel ion chambers was used for all the chambers, using the same reference chamber, a Farmer NE-2571. In the 170 MeV proton beam all the ND factors yielded consistent absorbed dose determinations within the estimated experimental uncertainties. This finding calls into question the value of the product kattkm for the IC-18 chamber given by the IAEA Code of Practice used in this comparison, and points at possible chamber to chamber variations that theoretical kattkm factors cannot predict. The investigations enabled the determination of the Pwall(60Co) factor of the Roos FK-6 plane parallel chamber, yielding 1.003 +/- 0.5%, and a correction for the effect of the aluminium central electrode of NE-2571 chambers in proton beams, equal to 1.003 +/- 0.4%. Two of the chambers (the plane parallel FK-6 and the modified cylindrical NE-2571) were provided with calibration factors in terms of absorbed dose to water, Nw, at the quality of 60Co by the Primary Standard Dosimetry Laboratory in Germany (PTB). Using the Nw formalism excellent agreement was found with the determination based on the experimental ND, giving support to the implementation of the NW procedure in therapeutic proton beams.

Humans↗
PubMed1995

Predictors for non- and slow progression in human immunodeficiency virus (HIV) type 1 infection: low viral RNA copy numbers in serum and maintenance of high HIV-1 p24-specific but not V3-specific antibody levels.

To gain insight into determinants that define the duration of the asymptomatic period preceding AIDS, groups of long-term asymptomatic (LTA) person (> 7 years of follow-up) and slow and rapid progressors of human immunodeficiency virus infection were studied. LTAs had no clinical manifestations of AIDS or immunologic abnormalities in 7 years of follow-up. RNA copy numbers, gag- and env-specific, and neutralizing antibody titers in serum were determined 1 and 5 years after seroconversion or entry into the cohort. Early in infection, before immunologic markers or clinical manifestations allowed group discrimination, subjects who were later classified as LTAs had significantly less serum viral RNA than progressors. No significant increase in virus load was found in progressors, indicating that the initial load defines clinical outcome. In slow progressors, high virus load was associated with high p24-specific antibody titers, suggesting that delay of clinical manifestations of AIDS may be related to the presence of high levels of p24-specific but not V3-specific antibodies.

Acquired Immunodeficiency Syndrome↗
PubMed1995

The predictive value of T cell function in vitro and pre-AIDS zidovudine use for survival after AIDS diagnosis in a cohort of homosexual men in Amsterdam.

The best independent predictors of survival after AIDS diagnosis were determined in 160 homosexual men from the Amsterdam Cohort Study (1987 CDC case definition). In a Cox model, all pre-AIDS laboratory markers gathered during follow-up in the study did not independently predict survival after AIDS. A second analysis, using data available only at AIDS diagnosis, revealed that T cell reactivity after stimulation with phytohemagglutinin and monoclonal CD3 antibodies and the CD4+ cell count at diagnosis were independent predictors of survival. In an interval-based Cox model, the predictive value of pre-AIDS zidovudine use was determined. One year after AIDS diagnosis, participants with pre-AIDS zidovudine use had a worse survival probability (relative hazard = 3.99). In conclusion, the survival probability of homosexual men with AIDS can be estimate adequately using information obtained at clinical AIDS diagnosis. Analysis revealed the important predictive value of T cell function tests in vitro.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Changes in lens connexin expression lead to increased gap junctional voltage dependence and conductance.

The differentiation of mouse lens epithelial cells into fiber cells is a useful model for studying the changes of the electrical properties of gap junction (cell-to-cell) channels that are induced by an alteration in connexin expression patterns. In this model, cuboidal lens epithelial cells differentiate into elongated fiber cells, and the expression of connexin43 (Cx43) in the epithelial cells is replaced with the production of high levels of Cx50 and Cx46 in the fiber cells. We now report a new procedure to isolate mouse lens fiber cell pairs suitable for double whole cell patch-clamp analysis. Analysis was also performed for fiberlike cell pairs differentiated from epithelial cells in culture. Voltage dependence and unitary conductance of fiber cell gap junction channels were determined and compared with the corresponding values previously measured for the channels joining lens epithelial cells and for lens connexin channels formed in Xenopus oocyte pairs. Our results support a differentiation-induced shift toward stronger gap junctional voltage dependence and larger unitary conductances in the fiber cells. Our data further reflect a balanced functional contribution of Cx50 and Cx46 in the fiber cell-to-cell channels rather than a predominance of a single connexin.

Animals↗
PubMed1994

Apoptosis in L929 cells expressing a CD40/Fas chimeric receptor: dissociation of stimulatory from inhibitory death signalling functions.

A chimeric transmembrane receptor was constructed by fusing the extracellular domain of human CD40 to the transmembrane/intracellular domain of human Fas. When stably overexpressed in L929, the chimera retained the ligand binding specificity of CD40 and the basic signalling properties of Fas since an apoptotic response could be induced in a dose-dependent manner upon administration of recombinant, soluble CD40 ligand trimer or immobilized antiCD40 antibodies. However, this apoptotic response was independent of actinomycin D which is in contrast to results previously reported for L929 cells stably expressing wildtype human Fas. A labile protein factor was postulated to be responsible for inhibition of Fas-induced apoptosis in these cells. The apoptotic Fas signal tranduced by the chimeric CD40/Fas receptor is not regulated by this putative inhibitor. Our data suggest that the extracellular domains of CD40 and Fas form functionally similar mono- and multimeric structures and that the extracellular domain of Fas participates in the regulation of Fas-specific signal transduction.

Animals↗
PubMed1994

Characteristics of long-term asymptomatic infection with human immunodeficiency virus type 1 in men with normal and low CD4+ cell counts.

From a cohort study of homosexual men in Amsterdam, 61 human immunodeficiency virus (HIV)-infected men who had remained asymptomatic for at least 7 years were identified. In a nested case control study, these men were compared with 142 men who progressed symptomatic HIV infection (CDC class IV) within 7 years, regarding laboratory markers, sexual behavior, psychologic coping, and drug use. Of the 61 long-term asymptomatic men, 13 had a CD4+ cell count > or = 500/mm3 after 7 years; in 2 of these 13, the CD4+ cell count had not declined during follow-up. Independent of CD4+ cell count, long-term asymptomatic HIV-1 infection was characterized by stable T cell reactivity after stimulation with monoclonal CD3 antibodies, seropositivity for antibodies to HIV core proteins, and the absence of hepatitis B markers. No association with markers of high-risk sex or the recreational use of drugs was found. Long-term asymptomatic men had a slightly lower score regarding the coping behavior active problem-solving; no other associations with coping behaviors were found.

Adult↗
PubMed1994

1H magnetic resonance imaging of freezing and thawing in freeze-tolerant frogs.

Proton magnetic resonance imaging (MRI) of the processes of freezing and thawing in the wood frog Rana sylvatica provided noninvasive and real-time analysis of the mode of ice propagation through the body of a freeze-tolerant vertebrate. MRI revealed a directional movement of ice from the exterior inward that required several hours to reach completion. Freezing in core organs such as liver, which produces and exports cryoprotectant, and heart, which circulates it, was delayed and occurred well after the organs were surrounded by extraorgan ice. Natural thawing was a very different process; thawing began uniformly throughout the body, but core organs melted more rapidly than peripheral ones, an adaptation that may be key to the early restoration of heartbeat and breathing. The images presented demonstrate the sensitivity and power of MRI and its potential to become a critical monitoring technology in the development of cryopreservation techniques for mammalian organ explants.

Acclimatization↗
PubMed1994

Differential expression of two gap junction proteins in corneal epithelium.

Two distinct gap junction proteins (connexins) are expressed in rat corneal epithelium in a way which parallels cellular differentiation processes in this tissue. Connexin43 is restricted predominantly to the basal cells of the corneal epithelium and is present in significantly reduced amounts compared to the situation in the adjacent conjunctival epithelium. In contrast, a gap junction protein recognized by antibodies against MP70 which is the ovine homolog of mouse connexin50, is strongly expressed in the corneal epithelium and is present in the basal cells, wing cells and surface cells. While the functional significance of this differential expression of corneal epithelial connexins has yet to be established, the corneal epithelium is the third avascular tissue besides lens and heart valves which expresses a gap junction protein recognized by anti-MP70 antibodies.

Animals↗
PubMed1994

Electrical properties of mammalian lens epithelial gap junction channels.

PURPOSE: To establish an "electrical fingerprint" for the gap junction channels between mammalian lens epithelial cells. METHODS: The double whole cell patch clamp technique was applied to isolated cell pairs obtained from mouse lens epithelium and a continuous cell line of lens epithelial cells derived from the sheep lens (SLE 2.1). RESULTS: The junctional conductance in mouse lens epithelial cells and in cultured SLE 2.1 cells was found to be moderately voltage dependent. SLE 2.1 cells were analyzed in more detail. The voltage dependence could be described by a Boltzmann distribution with Vo = +/- 63.1 mV and Gmin = 0.34. In cell pairs that exhibited spontaneously low junctional conductance, single channel events could be distinguished. Single gap junction channel currents had a linear current-voltage relationship. A frequency histogram of single channel conductances from eight cell pairs had three major peaks of 35, 60 and 97 pS. CONCLUSION: The electrical properties of gap junction channels between mammalian lens epithelial cells were virtually identical to those previously reported for transfected cell lines expressing connexin43. The authors' physiological data are therefore in agreement with molecular studies that have identified connexin43 as the major connexin of lens epithelial cells.

Animals↗
PubMed1993

[Comparative use of MESAM IV and polysomnography in sleep-related respiratory disorders].

The high prevalence of sleep-related respiratory disturbances among the male population requires development of reliable outpatient measurement systems enabling the selection of patients to be admitted to the sleep laboratory. MESAM IV is such a system. It can record for up to 18 hours via four sensors a patient's snoring sounds, heart rate, oxygen saturation and posture. To test the reliability of the instrument we compared parallel night measurements by MESAM IV and polysomnography (PSG) via the respective Respiratory Disturbance Indices (RDI = number of apnoeas plus hypopnoeas per hour). The group of subjects studied numbered 68 patients of the sleep laboratory suspected of having sleep-related respiratory disturbances (age 18-78 years, average 50.8 yrs.; height 164-192 cm, av. 175.2 cm; weight 40-160 kg, av. 99.3 kg; body mass index 13.8-49.5, av. 32.3). Assessment of the MESAM measurements was effected on the one hand by means of a computer programme (version 1.2) that is part of the system, and on the other hand by 3 independent evaluators, two of whom were already experienced in MESAM evaluation. Each evaluator was unaware of all personal and clinical data of the patients and of the results obtained by the other evaluators. Visual assessment was performed according to fixed criteria with the inclusion of all four measurement signals of the system, whereas two mutually independent respiratory disturbance indices (RDI) were calculated by computer evaluation. The results of the various MESAM IV evaluations were compared with those of polysomnography.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

[Sleep disorders and use of psychotropic drugs in 6-year-old children].

The purpose of this prospective survey, conducted over a two years period, was to study the use of psychoactive drugs among six year-old children in the Bas-Rhin administrative "département", of eastern France. The factors analysed were family environment, after-school time, the child's sleep, the locality where the child lived and the drugs used. The child was examined by school doctors, in the presence of the parents, at the compulsory consultation at the start of first-year infant school. The study was exhaustive. Of the 11,274 children examined, 12.1% used a psychoactive drug, although only 1% were considered by their parents to be suffering from insomnia. Of the children using drugs, 32% had used them for more than a year, 24% for more than two years and 11% for more than three years. Consumption was also shown to vary greatly between different localities; in some areas the proportion of children using drugs was more than 50%.

Child↗