PubMed Health⌕ Search

Biomedical subjects

E Roessler

Publications and source records attributed to E Roessler.

At least 55 records · Page 3Linked to original sources

The interleukin 2 receptor (IL-2R): the IL-2R alpha subunit alters the function of the IL-2R beta subunit to enhance IL-2 binding and signaling by mechanisms that do not require binding of IL-2 to IL-2R alpha subunit.

Interleukin 2 (IL-2)-mediated signaling through its high-affinity receptor involves a complex interrelationship between IL-2 and two IL-2-binding chains, IL-2R alpha and beta chains. Previously with the reagents available it was difficult to define functional interactions between these two IL-2R subunits involved in IL-2 binding and signal transduction. To extend our understanding of the interplay between the two binding subunits we have done studies with the monoclonal antibody HIEI, which interferes with interaction of IL-2R alpha and beta chains (IL-2R alpha and IL-2R beta, respectively). Furthermore, we used two forms of IL-2, recombinant native IL-2 and F42A, an IL-2 analog (Phe-42----Ala substitution) that binds only to IL-2R beta. Analog F42A manifested 75-100% of the bioactivity of wild-type IL-2. This observation is inconsistent with the strict hierarchical IL-2-binding affinity conversion model previously proposed by Saito and coworkers [Saito Y., Sabe, H., Suzuki, N., Kondo, S., Ogura, T., Shimizu, A. & Honjo, T. (1988) J. Exp. Med. 168, 1563-1572] that predicted an ordered sequence of events in which IL-2 must first bind to IL-2R alpha before its interaction with IL-2R beta. Previous investigations using IL-2 variants were interpreted to show that IL-2R alpha merely acts to concentrate IL-2 to the cell surface and that no other meaningful interaction occurred between IL-2R alpha and IL-2R beta. However, our data are inconsistent with this view. We draw this conclusion on the basis of our observation that antibody HIEI, which reacts with an epitope of IL-2R alpha and interferes with interaction of this chain and IL-2R beta, inhibits the IL-2-dependent proliferative effects mediated by analog F42A. Furthermore, by blocking interaction of IL-2R alpha and IL-2R beta with the antibody HIEI, a decrease in the affinity of radiolabeled analog F42A for IL-2R beta was seen. In our proposed model IL-2R alpha contributes several functions to IL-2-mediated signaling through the high-affinity IL-2R. These functions include concentration of IL-2 within the two-dimensional surface of the plasma membrane as well as alteration of the functional capacity of IL-2R beta, an effect that does not require prior binding of IL-2R to IL-2R alpha. The IL-2R alpha-mediated augmentation of IL-2R beta functions involves affinity conversion of IL-2R beta, increasing its affinity for IL-2, and may involve facilitation of Il-2-mediated signaling after binding of IL-2 to this IL-2R beta.

Amino Acid Sequence↗

[A 2-year follow-up of a program for the control of cardiovascular risk factors among asymptomatic workers].

In 1987, a cardiovascular risk profile was obtained on 836 workers of the National Electricity Co in Santiago. There were 714 males and 125 females, the mean age was 45 years (ES +/- 0.3). Hypertension (systolic pressure > 160 or diastolic > 90 mmHg) was present in 17% of subjects, hypercholesterolemia (> 240 mg/dl or > 220 mg/dl associated to 2 other risk factors) in 17%, obesity (> 20% above ideal weight) in 33% and 29% were smokers. An advice to stop smoking, changes in the casino menu and hypertension, obesity and hypercholesterolemia's control programs were offered. These were attended by 108 hypertensives, 141 subjects with hypercholesterolemia and 104 obese individuals with an attendance rate of 64%, 75 and 77% respectively. Measurements repeated 2 years later revealed a reduction in diastolic pressure of 3.3 +/- 1.1 mmHg (p < 0.004) only in adherent subjects. Cholesterol levels were reduced by 24 +/- 3 mg/dl (p < 0.001) with no differences for non participants, adherent and non adherent subjects. Adherent obese subjects reduced their weight by 2.2 +/- 0.4 kg (p < 0.001). There was no change in the number of smokers.

Cardiovascular Diseases↗

[Preventive medical examination in asymptomatic workers: design and initial outcome of an institutional program].

We have designed a preventive medical examination program for workers of an electric company in Santiago, Chile. The first stage, directed mainly to identification of cardiovascular risk factors was completed in 1987. 1006 males and 163 females with mean age 45 +/- 9.4 years (range 22-65) were screened. High blood pressure mainly of mild degree was detected in 17.6% of subjects (57% of them were new cases). Total cholesterol above 220 mg/dl and HDL cholesterol below 40 mg/dl were present in 33% and 22%, respectively. Obesity (body weight > 120% of ideal weight for height) was present in 19%, and body mass index was above 27 in 25% of subjects. 23% of males and 31% of females smoked 1 or more cigarettes a day and 2% had an abnormal non-fasting glucose level. A total of 750 workers have at least 1 risk factor that should be corrected. No cases of cancer were detected by Papanicolaou and mammography. A positive correlation was found among LDL cholesterol, age and triglyceride levels and HDL was negatively correlated to triglycerides, blood glucose and obesity. A multivariate analysis of these factors revealed that only age was related to LDL levels and triglycerides to HDL levels. This health prevention program may help a significant number of asymptomatic workers by detecting risk factors that need correction in order to decrease mortality and morbidity in this population.

Adult↗

Mild hypoglycemia and impairment of brain stem and cortical evoked potentials in healthy subjects.

To evaluate the impact of mild hypoglycemia on CNS function in healthy adults, we measured brain stem auditory evoked potentials and P300 potentials (elicited by cognitive processing of auditory stimuli) during hypoglycemic or euglycemic insulin clamps (80 mU.m-2.min-1). In the hypoglycemic clamp study (n = 8), plasma glucose was allowed to fall from 4.6 to 3 mM in hourly approximately 0.5-mM steps and subsequently returned to euglycemic baseline levels. In the euglycemic clamp study (n = 8), plasma glucose was maintained at baseline levels throughout. Neither brain stem nor P300 responses changed during the euglycemic control study; symptoms and counterregulatory hormones were also unaffected. During the hypoglycemia study, epinephrine and growth hormone rose once plasma glucose reached 3.4 +/- 0.1 mM. Brain stem and P300 potentials remained unchanged until the 3-mM glucose step, when neurophysiological changes suddenly developed in conjunction with reported symptoms. At this glucose level, the wave V component of the brain stem potential was selectively altered in 7 of 8 subjects. Furthermore, P300 latency significantly increased, and amplitude diminished. Changes in both brain stem and cortical (P300) responses reversed when euglycemia was restored. We conclude that modest reductions in plasma glucose (to 3 mM) produce marked alterations in both brain stem and cortical responses to auditory stimuli. These changes in neural function appear at the same time as symptoms and follow rather than precede the rise in counterregulatory hormones during hypoglycemia. Our data suggest that the adverse effects of mild hypoglycemia on brain function are not limited to higher centers but also involve the brain stem.

Adult↗

Characterization of transferable plasmids from Shigella flexneri 2a that confer resistance to trimethoprim, streptomycin, and sulfonamides.

A set of plasmids conferring resistance to several antibiotics, including the combination of trimethoprim and sulfamethoxazole, has been isolated from Escherichia coli following conjugative cotransfer from a clinical isolate of Shigella flexneri 2a. One of the plasmids, pCN1, was shown by subcloning and DNA sequencing to carry a gene encoding a trimethoprim-insensitive dihydrofolate reductase identical to that found in E. coli transposon 7. This plasmid was also shown to confer resistance to both streptomycin and spectinomycin by production of an adenylyltransferase that inactivated the drugs and the gene encoding this enzyme has also been sequenced. A second plasmid from the set, pCN2, was shown to inactivate streptomycin by a phosphotransferase mechanism and also to confer resistance to sulfonamides. The third plasmid from the set could not be correlated with a drug-resistance phenotype, but does appear to play a crucial role in plasmid mobilization.

Base Sequence↗

Analysis of mobilization elements in plasmids from Shigella flexneri.

The mobilization properties of three plasmids were examined after cotransfer from Shigella flexneri to Escherichia coli. The largest plasmid, pCN1, was shown to be a conjugative R factor that could promote its own transfer and allow cotransfer of a 4.1-kilobase plasmid, pCN3; mobilization of the third plasmid, pCN2 (6.3 kilobases), required the presence of both pCN1 and pCN3. Sequences from pCN2 and pCN3 homologous to the bom (basis of mobilization) sites of ColE1 and pBR322 were localized by analysis of site-specific deletion derivatives generated in vivo during the transfer of composite plasmids and were characterized by DNA sequencing.

Base Sequence↗

[Potency disorders in the aging men. Psychiatric aspects].

Based on experiences gained in psychiatric counselling for patients with problems specific to climacterium virile, the climacterium virile as a time of crisis is compared to the period of puberty. Suggestions are given to provide a crisis management for this particular period of life in order to improve the chances for a satisfactory development during the subsequent years of life.

Age Factors↗