Showing papers by "University of Vienna published in 1993"

Does Fairness Prevent Market Clearing? An Experimental Investigation

Abstract: This paper reports the results of an experiment that was designed to test the impact of fairness on market prices. Prices were determined in a one-sided oral auction, with buyers as price-makers. Upon acceptance of an offer, sellers determined the quality of the good. Buyers offered prices that were substantially above the market-clearing level and expected sellers to respond with high quality levels. This expectation was, on average, confirmed by the behavior of sellers. These results provide, therefore, experimental support for the fair wage-effort theory of involuntary unemployment. I. INTRODUCTION Fairness is an elusive term. Yet, in actual business practice the parties involved in a transaction seem to refer quite frequently to the notion of fairness. This observation had already been made by Marshall [1925], who wrote: ". . . the phrase is constantly used in the market place; it is frequent in the mouths both of employers and the employed; and almost every phrase in common use has a real meaning, though it may be difficult to get at." In a recent study Blinder and Choi [1990] asked nineteen managers whether they and their workers would perceive a wage reduction to take advantage of labor market slack as (a) completely fair, (b) acceptable, (c) unfair, or (d) very unfair. While three managers considered this as an irrelevant question, all but one of the remaining sixteen said that such a wage cut is unfair or very unfair. Moreover, all but one believed that their workers would consider this wage cut as unfair or very unfair. In their study of community standards of fairness for the setting of prices and wages, Kahneman, Knetsch, and Thaler [1986] infer rules of fairness for conduct in the market from their interviewees' answers to hypothetical questions. Their empirical findings confirm the existence of such rules. However, what people say is one thing, but what they actually do may be quite a different thing. The possible divergence between

Apoptotic death in epithelial cells: cleavage of DNA to 300 and/or 50 kb fragments prior to or in the absence of internucleosomal fragmentation.

Abstract: To date, apoptosis has been characterized biochemically by the production of 180-200 bp internucleosomal DNA fragments resulting from the activation of an endonuclease(s). The principal morphological feature of apoptosis is the condensation of chromatin and it has been assumed that this may reflect the oligonucleosomal fragmentation pattern. We have re-examined this dogma by comparing the biochemical and morphological features of cell death in several epithelial cell types (HT-29-I1 colon adenocarcinoma, CC164 mink lung, DU-145 human prostatic carcinoma and MCF-7 human breast adenocarcinoma) and one mesenchymal cell line (H11ras-R3 ras-transformed rat fibroblasts). Cell death was induced either by serum deprivation, TGF-beta 1 or etoposide, or by leaving cells to reach confluence. Cell death was assessed with respect to detachment from monolayers, morphological changes and DNA integrity. The DNA-binding fluorophore Hoechst 33258 revealed chromatin condensation patterns consistent with apoptotic cell death in all cell types except MCF-7 cells. Using field inversion gel electrophoresis in conjunction with conventional 2% agarose gel electrophoresis, cleavage of DNA to 50 kbp fragments was observed in all cases except MCF-7 cells. This preceded the appearance of oligonucleosomal fragments in HT-29-I1, CC164 and H11ras-R3 cells. Although the DNA of DU-145 cells fragmented into 50 kbp units, and although the cells exhibited classical apoptotic morphology, no subsequent internucleosomal cleavage was observed. These results suggest that changes in the integrity of DNA indicative of the release of chromatin loop domains occur before cleavage at internucleosomal sites is initiated and that the latter is not an essential step in the apoptotic process.

Fibrinogen as a cardiovascular risk factor: a meta-analysis and review of the literature.

Abstract: Purpose To evaluate the possibility that fibrinogen represents a cardiovascular risk factor. Data identification A computerized literature search (1980 to 1992) identified all published epidemiologic studies on fibrinogen and cardiovascular disease. Clinical and basic research data were found by separate searches. References of all papers thus obtained were studied and relevant papers included. Study selection Six prospective epidemiologic studies were included in a meta-analysis (one study was excluded because the study population was non-representative). Clinical papers were reviewed separately for other evidence of causation. Data extraction The correlation of fibrinogen levels on the subsequent incidence of myocardial infarction, stroke, and peripheral arterial occlusive disease was assessed and the causality of the association was analyzed. Calculations were made to examine fibrinogen level (in tertiles) versus cardiovascular risk. Odds ratios of high versus low tertile were computed. Results of data analysis All prospective studies showed that fibrinogen was associated with subsequent myocardial infarction or stroke. A total of 92,147 person-years was covered by these investigations. Odds ratios varied between 1.8 (95% CI, 1.2 to 2.5) in the Framingham and 4.1 (CI, 2.3 to 6.9) in the GRIPS study, with a summary odds ratio of 2.3 (CI, 1.9 to 2.8). Associations existed between fibrinogen and other cardiovascular risk factors, but after multivariate analysis, only the association between fibrinogen and cardiovascular events remained. The majority of the preconditions for causality were fulfilled, indicating that fibrinogen is pathophysiologically related to cardiovascular events. Conclusions Fibrinogen can be considered a major cardiovascular risk factor. Future studies of cardiovascular morbidity and death should include this variable.

Randomised comparison of combination chemotherapy plus supportive care with supportive care alone in patients with metastatic colorectal cancer.

Abstract: OBJECTIVES--To compare the length of survival and quality of life in patients given combination chemotherapy in addition to supportive care and in patients given only supportive care. DESIGN--Randomised study. SETTING--Gastrointestinal oncology departments. PATIENTS--40 previously untreated patients with histologically confirmed, measurable colorectal cancer that was locally recurrent or metastatic. INTERVENTIONS--Patients were allocated randomly to receive chemotherapy or only supportive care in a ratio of 2:1 according to performance status, metastatic disease of the liver, and weight loss in the six months before entering the study. Chemotherapy consisted of four week cycles of intravenous leucovorin (200 mg/m2/day) followed by 5-fluorouracil (550 mg/m2/day) and cisplatin (20 mg/m2/day), each drug being given on the first four days of the cycle. MAIN OUTCOME MEASURES--Length of survival and quality of life score with an optimised functional living index-cancer scale. RESULTS--Overall survival was significantly longer for patients given chemotherapy (11.0 months) than for those receiving supportive care alone (5.0 months; p = 0.006). Despite common association of chemotherapy with mild to moderate gastrointestinal symptoms, there was no significant difference between the two groups in global or subgroup quality of life scores. In patients with abnormal scores before treatment, quality of life seemed better in the chemotherapy arm. CONCLUSIONS--In this sample of patients with disseminated colorectal cancer the chemotherapy regimen was an effective form of palliative treatment.

A Saccharomyces cerevisiae UAS element controlled by protein kinase A activates transcription in response to a variety of stress conditions.

Abstract: Transcription of the Saccharomyces cerevisiae CTT1 gene encoding the cytosolic catalase T is activated by a variety of stress conditions: it is derepressed by nitrogen starvation and induced by heat shock. Furthermore, it is activated by osmotic and oxidative stress. This study shows that a CTT1 upstream region previously found to be involved in nitrogen, cAMP and heat control (base pairs -382 to -325) contains a UAS element (STRE, -368 to -356), which is sufficient for the activation of a reporter gene by all types of stress acting on CTT1. Gel retardation experiments demonstrated the existence of a factor specifically binding to STRE, but to a lesser extent to mutated elements having partly or entirely lost the ability to mediate stress control. Heat activation of STRE, but not of a canonical heat shock element, is enhanced by a ras2 defect mutation, which enhances thermotolerance, and is dramatically reduced by a bcy1 disruption mutation, which decreases thermotolerance. It can be hypothesized, therefore, that the novel stress control element is important for the establishment of induced stress tolerance.

The prognostic significance of proliferating cell nuclear antigen, epidermal growth factor receptor, and mdr gene expression in colorectal cancer

Abstract: Background. Proliferating cell nuclear antigen (PCNA), a proliferation marker, epidermal growth factor receptor (EGFR), a glycoprotein that plays a role in tumorigenesis by binding the mitogenic epidermal growth factor, and P-glycoprotein, the mdr gene product, are considered to be of prognostic relevance in different tumor types. Parameters that allow prediction of the course of disease in colorectal cancer would aid the development of improved treatment strategies. Methods. Immunohistochemical staining was performed on paraffin-embedded sections of 82 colorectal adenocarcinomas and 18 lymph node metastases. EGFR and P glycoprotein expression was evaluated semiquantitatively; PCNA expression was analyzed quantitatively. Results. An inverse relationship between the percentage of PCNA-positive cells and survival times could be demonstrated, survival differed significantly among the quartiles (P < 0.02). The median and range of the percentage of PCNA-positive cells in primary tumors and lymph node metastases were similar. The extent of EGFR expression also revealed significant differences concerning survival times; patients with more than 50% stained tumor cells had a poorer prognosis than those with less than 50% stained cells. P-glycoprotein expression was found to have no influence on survival. Conclusions. Knowledge of the percentage of PCNA-positive cells could be especially helpful in deciding whether to treat patients with localized disease further because adjuvant chemotherapy affects mainly dividing cells and should, therefore, be more successful in tumors with high proliferative activity.

Bone marrow derived elements and resident microglia in brain inflammation

Abstract: Infection of the central nervous (CNS) system by the human immunodeficiency virus (HIV) depends on the migration of infected hematogenous cells into the brain. We thus used quantitative light and electron microscopic immunocytochemistry to study the homing and turnover of bone marrow derived cells in the CNS in radiation bone marrow chimeras under normal conditions and in experimental autoimmune encephalomyelitis (EAE) as an experimental model of brain inflammation. Our studies suggest the following conclusions. First, the central nervous system is continuously patrolled by a small number of T-lymphocytes and monocytes. Meningeal and perivascular monocytes are slowly replaced by hematogenous cells under normal conditions, and this turnover is accelerated in the course of inflammation. In contrast, resident microglia represent a very stable cell pool, which in adult animals is only exceptionally replaced by hematogenous cells, even after recovery from severe brain inflammation. Second, although in bone-marrow-chimeric animals resident microglia, astrocytes, and ependymal cells are not able to present antigen to Lewis T-lymphocytes, the inflammatory reaction in EAE is qualitatively and quantitatively similar in these animals compared to fully histocompatible Lewis rats. Finally, resident microglia express the macrophage activation antigen ED1. Thus, microglia cells appear to function as effector cells in EAE lesions.

Major role of ultraviolet-B in controlling bacterioplankton growth in the surface layer of the ocean

Abstract: THERE is evidence that the potentially harmful solar ultraviolet-B (UV-B, 280–320 mm) radiation penetrates much deeper into the ocean's water column than previously thought1,2. UV-B radiation is also responsible for photochemical degradation of refractory macromolecules into biologically labile organic compounds3,4. It thus seems reasonable to assume that UV-B radiation might influence the cycling of organic matter in the sea, which is believed to be largely mediated by bacterioplankton5. Here we report that bacterioplankton activity in the surface layers of the oceans is suppressed by solar radiation by about 40% in the top 5 m of the water column in nearshore waters, whereas in oligotrophic open oceans suppression might be detectable to a depth of >10 m. Bacterioplankton from near-surface (0.5 m depth) waters of a highly stratified water column were as sensitive to surface UV-B radiation as subpycnocline bacteria, indicating no adaptative mechanisms against surface solar radiation in near-surface bacterioplankton consortia. Surface solar radiation levels also photochemically degrade bacterial extracellular enzymes. Thus elevated UV-B radiation due to the destruction of the stratospheric ozone layer might lead to reduced bacterial activity and accompanying increased concentration of labile dissolved organic matter in the surface layers of the ocean as bacterial uptake of this is retarded.

Muller's ratchet and mutational meltdowns.

Abstract: We extend our earlier work on the role of deleterious mutations in the extinction of obligately asexual populations. First, we develop analytical models for mutation accumulation that obviate the need for time-consuming computer simulations in certain ranges of the parameter space. When the number of mutations entering the population each generation is fairly high, the number of mutations per individual and the mean time to extinction can be predicted using classical approaches in quantitative genetics. However, when the mutation rate is very low, a fixation-probability approach is quite effective. Second, we show that an intermediate selection coefficient (s) minimizes the time to extinction. The critical value of s can be quite low, and we discuss the evolutionary implications of this, showing that increased sensitivity to mutation and loss of capacity for DNA repair can be selectively advantageous in asexual organisms. Finally, we consider the consequences of the mutational meltdown for the extinction of mitochondrial lineages in sexual species.

Statistics of RNA secondary structures

Abstract: A statistical reference for RNA secondary structures with minimum free energies is computed by folding large ensembles of random RNA sequences. Four nucleotide alphabets are used: two binary alphabets, AU and GC, the biophysical AUGC and the synthetic GCXK alphabet. RNA secondary structures are made of structural elements, such as stacks, loops, joints, and free ends. Statistical properties of these elements are computed for small RNA molecules of chain lengths up to 100. The results of RNA structure statistics depend strongly on the particular alphabet chosen. The statistical reference is compared with the data derived from natural RNA molecules with similar base frequencies. Secondary structures are represented as trees. Tree editing provides a quantitative measure for the distance dt, between two structures. We compute a structure density surface as the conditional probability of two structures having distance t given that their sequences have distance h. This surface indicates that the vast majority of possible minimum free energy secondary structures occur within a fairly small neighborhood of any typical (random) sequence. Correlation lengths for secondary structures in their tree representations are computed from probability densities. They are appropriate measures for the complexity of the sequence-structure relation. The correlation length also provides a quantitative estimate for the mean sensitivity of structures to point mutations.

Condensation of the chromatin at the membrane of an apoptotic nucleus is not associated with activation of an endonuclease

Abstract: A current hypothesis holds that chromatin fragmentation into oligonucleosomal patterns is an early event during apoptosis. In contrast, induction of apoptosis in cultured hepatocytes by TGF-beta 1 was not associated with DNA fragmentation into oligonucleosomes in hepatocyte monolayers and apoptotic fragments. For a more rigorous test of the hypothesis we performed a number of experiments. We compared nuclear changes resulting from TGF-beta 1 with those induced by Ca2+, a known activator of endonuclease. The morphology of apoptotic and Ca(2+)-treated nuclei was different as judged by DNA staining with Hoechst 33258. Likewise, electron microscopy of apoptotic nuclei showed characteristic condensation of the chromatin as well as dissolution of the nucleolar structure and nuclear fragmentation, changes not seen after Ca2+ treatment, after three hours of incubation. Analysis of DNA fluorescence of nuclei by FACS revealed that treatment with Ca2+ reduced the signal by 20%. In contrast, nuclei from TGF-beta 1-treated hepatocytes did not exhibit a reduced signal and after sorting by FACS, apoptotic nuclei remained in the 2N and 4N fractions. The absence of detectable DNA fragmentation in apoptotic nuclei was further verified by in situ nick translation, not only in hepatocytes but also in a mouse lymphoma cell line. From these findings we conclude that activation of an endonuclease is not an early event on the pathway to morphologically recognizable apoptosis.

A new signature scheme based on the DSA giving message recovery

Abstract: In this paper we present a modification of the DSA which allows signatures with message recovery. The new public key signature scheme is then applied to create (a) an identity-based public key system without restrictions in trust and (b) a one-pass key exchange protocol with mutual authentication.

Forced-air warming maintains intraoperative normothermia better than circulating-water mattresses.

Abstract: The hypothesis that forced-air warming preserves core temperature better than circulating-water mattresses was tested in: (a) 16 adults undergoing major maxillofacial surgery, including radical node resection and flap reconstruction; (b) 53 adults undergoing hip arthroplasty, having approximately 25% of their body surface area available for warming; (c) 20 infants undergoing minor maxillofacial surgery; and (d) 10 young children undergoing pelvic or femoral osteotomies. Patients having each type of surgery were randomly assigned to forced-air warming (approximately 40 degrees C) or conductive warming using a full-length circulating-water mattress at 40 degrees C. Forced-air warming was applied to the legs of the adults undergoing maxillofacial surgery and to one arm, the shoulders, and the neck in the adults undergoing hip arthroplasty; a U-shaped, tubular forced-air cover was positioned around the pediatric patients. Core temperatures increased in all patients given forced-air warming and decreased or remained constant in those without active warming. Furthermore, we needed to decrease the temperature of the warmer from high to medium (approximately 37 degrees C) in most patients assigned to forced-air warming to prevent hyperthermia. After 15 h of anesthesia, rectal temperatures in the adults undergoing maxillofacial surgery were 3.4 degrees C higher in the forced-air group (P < 0.01). After 4 h of anesthesia, esophageal temperatures had increased 0.8 +/- 0.5 degrees C in the patients warmed with forced-air and decreased 0.8 +/- 0.3 degrees C in those warmed by circulating-water mattresses (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Bone-marrow oedema syndrome and transient osteoporosis of the hip. An MRI-controlled study of treatment by core decompression.

Abstract: Bone-marrow oedema syndrome (BMOS) of the hip gives a characteristic MRI pattern, in association with severe pain, non-specific focal loss of radiological density and a positive bone scan. In our MRI-controlled study, nine patients with non-traumatic BMOS in ten hips all had core decompression. Bone-marrow pressure measurements and intraosseous venography in five cases showed pathological values. All patients had immediate relief of pain, with return of MRI signals to normal after three months. Regular review was continued for at least 24 months with serial clinical radiological and MRI assessment. At a mean follow-up of 33 months all patients remained free of pain with normal radiographs and MR scans. The histological evaluation of undecalcified sections obtained from eight core decompressions confirmed the presence of bone-marrow oedema, with necrotic and reparative processes involving bone and marrow similar to those of early avascular necrosis but with no evidence of 'osteoporosis'. These findings support the assumption that BMOS may be the initial phase of non-traumatic avascular necrosis. In most patients BMOS will have a self-limiting course, but the duration of symptoms may be reduced by core decompression treatment.

Clinical trials of agents that reverse multidrug resistance. A literature review.

Abstract: Background The discovery of the P-170 glycoprotein as a mediator of multidrug resistance (MDR) represents one of the most important research accomplishments in antineoplastic pharmacology during the last decade Demonstration of P-170 in epithelial tissues, untreated and chemotherapeutically pretreated human malignancies, and identification of various agents capable of reversing resistance in vitro generated enthusiasm for clinical studies throughout the world The authors provide an overview of the current status of clinical investigations of MDR1 reversing agents in hematologic and solid malignancies Methods The authors performed an extensive literature search and selected more than 70 articles concerning the potential clinical relevance of P-glycoprotein/MDR1 modulating agents Information abstracted included type of reverting agent and chemotherapeutic regimen, number of patients, tumor type, histologic proof of P-glycoprotein expression, and objective response rates Results Proof of the involvement of MDR1 in clinical drug resistance has been slow to accumulate, primarily because of difficulties in adapting assays of MDR1 expression and in planning appropriate trials Pilot studies have shown that verapamil, cyclosporine, and other chemosensitizers may reverse resistance in a subset of patients, but significant (cardiovascular) side effects are common For leukemias, lymphomas, and multiple myeloma, response rates of 60–80% may be achieved with the potential for cure, whereas in solid tumors, only a few patients appear to benefit Conclusions Because of predominantly negative results and unanswered fundamental questions regarding the biology of P-glycoprotein, additional clinical trials with less toxic modulators or their combination are appropriate to delineate optimal strategies for MDR1 reversal and to define the spectrum of responsive tumors Additional attention also must be given to the coexistence of other resistance mechanisms that may offer separate opportunities for modulation

Cold work hardening in stages IV and V of F.C.C. metals—I. Experiments and interpretation

Abstract: The paper presents numerous measurements which confirm stages IV and V to be general ranges of cold work deformation. Analogous to stage II, stage IV exhibits a linear athermal hardening with constant strain rate sensitivity and activation enthalpy. In stage IV the dislocation cell size is constant, while the dislocation density growth rate is markedly reduced compared with stages II and III. Features of stage V are analogous to stage III, the increase of strain rate sensitivity (decrease of activation enthalpy) indicating the onset of thermally activated dislocation annihilation. In stage V, the mechanism is identified as dislocation climb from observing subgrain formation and saturation in density of deformation induced vacancies. Comparisons with recent investigations of stage IV and V at high temperatures suggest a common picture of low and high temperature deformation which only requires principles of storage and annihilation for both screw and edge dislocations.

Four recombinant isoforms of Cor a I, the major allergen of hazel pollen, show different IgE‐binding properties

Abstract: Previous studies showed that pollens from trees of the order Fagales (e. g. birch, alder, hazel and hornbeam) all contain one major allergen. These proteins are cross-reactive between these tree species, and approximately 95% of tree-pollen-allergic patients display IgE binding to these allergens. Using the reported N-terminal amino acid sequence of the hazel pollen allergen Cor a I, it was possible to amplify Cor-a-I cDNA by use of the polymerase chain reaction. Four clones with cDNA inserts were isolated. All four clones contained an open reading frame of 477 nucleotides (159 amino acids) but differed in length of their 3′-non-coding regions. Within the overlapping regions, the nucleotide sequence of the 3′-non-coding regions of the four clones were nearly identical. The open reading frames coded for different isoforms of the major hazel pollen allergen, Cor a I. The clones were designated Cor a I/5, 6, 11 and 16, respectively. Comparison of the deduced amino acid sequences of these Cor a I isoforms revealed identities of 96–99%. The sequence identities between the Cor a I isoforms and Bet v I, the major birch pollen allergen, were 71–73% (80.5–83% similarity). Comparing amino acid sequences of Cor a I isoforms with the published sequences of Aln g I, the major allergen from alder, and Cor a I and isoforms, the major allergen from hornbeam, 75.5–76.7% identity (83.6–85% similarity) and 83.6–89.9% sequence identity (89.3–95% similarity), respectively, was found. The four Cor a I cDNAs were subcloned into plasmid pKK223-3 and expressed in Escherichia coli as non-fusion proteins; their capacity to bind serum IgE from tree-pollen-allergic patients was investigated. The four cloned isoforms showed an apparent molecular mass of 17 kDa in SDS/PAGE, identical to the natural, pollen-derived Cor a I. IgE antibodies from tree-pollen-allergic patients was reacted with all four recombinant isoforms. However, we noted marked differences in the IgE-binding patterns of the distinct isoforms. Furthermore, Cor a I/11 was the only isoform recognized by the anti-(Bet v I) mAb, BIP 1. Our results demonstrate that Cor a I isoforms display different antigenic properties, very likely due to few but significant changes in their amino acid sequences. These findings have implications for the development of reagents for diagnosis and immunotherapy of type I allergies.

Distribution of Viruses and Dissolved DNA along a Coastal Trophic Gradient in the Northern Adriatic Sea.

Abstract: The distribution of viral and other microbial abundances as well as the concentrations of dissolved DNA (D-DNA) along a trophic gradient in the northern Adriatic Sea were determined. Virus abundances, covering a range of 1.2 x 10 to 8.7 x 10 liter were on average 2.5-fold higher in eutrophic than in mesotrophic stations. A 2.5-fold enrichment was also measured for chlorophyll a concentrations, whereas the densities of bacteria and heterotrophic nanoflagellates were only approximately 1.5-fold higher. The frequency of bacteria containing mature phage increased linearly with bacterial abundance. Assuming that mature phage is only visible during the last 14 to 27% of the latent period (L. M. Proctor, A. Okubo, and J. A. Fuhrman, Microb. Ecol. 25:161-182, 1993), we estimated that between 3.5 and 7.3% of the bacterial population was infected at mesotrophic stations versus between 7.0 and 19.5% at eutrophic stations, indicating that the bacterial mortality due to viral lysis might increase with the degree of eutrophication. The frequency of bacteria with mature phage and the burst size varied significantly with the bacterial morphotype; rod-shape cells, the most abundant morphotype, showed low infection rates but a high burst size. Concentrations of D-DNA varied significantly with season but not with trophic conditions. The estimated percentage of viral DNA on total D-DNA concentrations averaged 17.1% (range, 0.7 to 88.3%). Some kind of interaction between heterotrophic nanoflagellates and viruses is proposed. We conclude (i) that the significance of viruses varies with changing trophic conditions and (ii) that viral activity may play a significant role in food web structure under changing trophic conditions.

Inhibition of experimental autoimmune encephalomyelitis by an antibody to the intercellular adhesion molecule ICAM-1.

Abstract: Experimental autoimmune encephalomyelitis (EAE) was induced in Lewis rats by active immunization with myelin from guinea pig spinal cord by the encephalitogenic myelin basic protein or by adoptive transfer using myelin basic protein-specific CD4-positive T cells. Treatment with purified monoclonal antibody (1A-29) to the intercellular adhesion molecule-1 and its F(ab')2 fragments efficiently suppressed active EAE. Control treatment with an irrelevant antibody or saline did not alter the course of the disease. Histological sections of the central nervous system showed a pronounced reduction of inflammatory infiltrates during treatment with antibody to intercellular adhesion molecule-1. In the adoptive transfer model of EAE, 1A-29 had only a minor effect. Proliferation assays on lymph node cells ex vivo from 1A-29- and saline-treated animals were performed. Administration of 1A-29 suppressed antigen-specific T-cell proliferation. The differential effects in EAE versus adoptive transfer EAE suggest that 1A-29 acts predominantly on the induction phase of the immune response and, to a lesser extent, on the transendothelial migration of T cells. We conclude that intercellular adhesion molecule-1-dependent pathways are critically involved in the pathogenesis of EAE and that antibodies to leukocyte adhesion molecules could be a novel therapeutic approach to autoimmune disease of the central nervous system.

Effect of growth hormone treatment on hormonal parameters, body composition and strength in athletes

Abstract: The effect of recombinant GH on strength, body composition and endocrine parameters in power athletes was investigated in a controlled study. Twenty-two healthy, non-obese males (age 23.4 +/- 0.5 years; ideal body weight 122 +/- 3.1%, body fat 10.1 +/- 1.0%; mean +/- SEM) were included. Probands were assigned in a double-blind manner to either GH treatment (0.09U (kg BW)-1 day-1 sc) or placebo for a period of six weeks. To exclude concurrent treatment with androgenic-anabolic steroids urine specimens were tested at regular intervals for these substances. Serum was assayed for GH, IGF-I, IGF-binding proteins, insulin and thyroxine before the onset of the study and at two-weekly intervals thereafter. Maximal voluntary strength of the biceps and quadriceps muscles was measured on a strength training apparatus. Fat mass and lean body mass were derived from measurements of skinfolds at ten sites with a caliper. For final evaluation only data of those 8 and 10 subjects in the two groups who completed the study were analyzed. GH, IGF-I and IGF-binding protein were in the normal range before therapy and increased significantly in the GH-treated group. Fasting insulin concentrations increased insignificantly and thyroxine levels decreased significantly in the GH-treated probands. There was no effect of GH treatment on maximal strength during concentric contraction of the biceps and quadriceps muscles. Body weight and body fat were not changed significantly during treatment. We conclude that the anabolic, lipolytic effect of GH therapy in adults depends on the degree of fat mass and GH deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

CD1 molecule expression on human monocytes induced by granulocyte-macrophage colony-stimulating factor.

Abstract: In this paper we demonstrate that granulocyte-macrophage CSF (GM-CSF) specifically induces the expression of CD1 molecules, CD1a, CD1b and CD1c, upon human monocytes. CD1 molecules appeared upon monocytes on day 1 of stimulation with rGM-CSF, and expression was up-regulated until day 3. Monocytes cultured in the presence of LPS, FMLP, PMA, recombinant granulocyte-CSF, rIFN-gamma, rTNF-alpha, rIL-1 alpha, rIL-1 beta, and rIL-6 remained negative. The induction of CD1 molecules by rGM-CSF was restricted to monocytes, since no such effect was observed upon peripheral blood granulocytes, PBL, and the myeloid cell lines Monomac1, Monomac6, MV4/11, HL60, U937, THP1, KG1, and KG1A. CD1a mRNA was detectable in rGM-CSF-induced monocytes but not in those freshly isolated. SDS-PAGE and immunoblotting analyses of CD1a mAb VIT6 immunoprecipitate from lysate of rGM-CSF-activated monocytes revealed an appropriate CD1a polypeptide band of 49 kDa associated with beta 2-microglobulin. Expression of CD1 molecules on monocytes complements the distribution of these structures on accessory cells, and their specific induction by GM-CSF strengthens the suggestion that CD1 is a family of crucial structures required for interaction between accessory cells and T cells.

Purification of two picornaviral 2A proteinases: Interaction with eIF-4.gamma. and influence on the in vitro translation

Abstract: A mammalian cell infected with a human rhinovirus or enterovirus has a much reduced capability to translate capped mRNAs (the host cell shutoff), while still allowing translation of uncapped viral RNA. Biochemical and genetic evidence suggests that the viral proteinase 2A induces cleavage of the eukaryotic initiation factor (eIF) 4 gamma (also known as p220) component of eIF-4 (formerly called eIF-4F). However, neither the mechanism underlying the specific proteolysis of eIF-4 gamma nor the influence of this cleavage on the translation of capped mRNAs has been clarified. Such studies have been hampered by a lack of large quantities of a purified 2A proteinase. Therefore, the mature proteinases 2A of human rhinovirus 2 and coxsackievirus B4 were expressed in soluble form in Escherichia coli. A four-step purification protocol was developed; 1 mg of highly purified 2A proteinase per gram wet weight of E. coli was obtained. Both enzymes cleaved directly eIF-4 gamma as part of the purified eIF-4 complex. Addition of HRV2 2A proteinase to HeLa cell cytoplasmic translation extracts resulted in eIF-4 gamma cleavage and drastically reduced the translation of capped mRNA; addition of purified eIF-4 restored translation to the initial level. However, translation of a reporter gene driven by the 5'-untranslated region of human rhinovirus 2 was translated 2-3-fold more efficiently in the presence of HRV2 2A proteinase.

Transforming growth factor-beta 1 as a signal for induction of cell death by apoptosis.

Abstract: Cell death by apoptosis is a major determinant of growth of normal tissues and tumours. The present study aimed to elucidate signal factors involved in its regulation. Epithelial cells in control liver, during regression of cyproterone acetate induced liver hyperplasia, in liver (pre)neoplasia and in uterus undergoing apoptosis in vivo show immunostaining for transforming growth factor beta 1 (TGF-beta 1) as detected by anti-pre(266-278) TGF-beta 1 antibodies. Positive immunostaining is also seen in a few intact cells of hyperplastic, regressing liver apparently preparing for apoptosis, but is virtually not found in hepatocytes of normal or growing liver nor in cells undergoing death by necrosis. Recombinant latency associated protein (rLAP, dimer of the pro-region non-covalently associated with the mature region) complex and mature TGF-beta 1 induce apoptosis in isolated hepatocytes cultured in vitro. These findings suggest an involvement of TGF-beta 1 in the induction of apoptosis in certain epithelia in vivo.