Disruption of vitamin D receptor-retinoid X receptor heterodimer formation following ras transformation of human keratinocytes

A partial resistance to the growth inhibitory influence of 1, 25-dihydroxyvitamin D3 is apparent when immortalized keratinocytes are transformed by the ras oncogene. The vitamin D receptor (VDR) was isolated, analyzed, and found to be identical in normal, immortalized, and ras-transformed keratinocytes. Subsequently, nuclear extracts from immortalized and ras-transformed keratinocytes were analyzed in gel mobility shift assays utilizing labeled vitamin D response elements or thyroid hormone response elements. A specific protein.DNA complex that was shown to contain VDR using an anti-VDR antibody was identified in both types of extracts; however, the addition of an anti-retinoid X receptor (RXR) antibody identified RXR in the complex of both normal and immortalized keratinocyte cell extracts, but not in ras-transformed keratinocytes. Furthermore, transfection of ras-transformed keratinocytes with wild-type human RXRalpha rescued VDR.RXR and thyroid hormone receptor.RXR complexes as demonstrated by a supershift in the presence of the anti-RXR antibody. Both cell lines were found to express RXRalpha message in equal amounts. Western blot analysis revealed that RXRalpha protein from ras-transformed keratinocytes was indistinguishable from that from immortalized keratinocytes and from control cells. These results suggest a causal relationship between resistance to the growth inhibitory influences of 1,25-dihydroxyvitamin D3 and disruption of the VDR.RXR complex in malignant keratinocytes.     

Polyclonal antibodies from blood and cerebrospinal fluid of patients with multiple sclerosis effectively hydrolyze DNA and RNA

It is known that in the blood of patients with some autoimmune diseases catalytically active antibodies hydrolyzing proteins, DNA, and RNA may be detected. In the present work homogeneous preparations of IgG antibodies (Ab) possessing high affinity for nucleic acids (NA) were obtained for the first time from blood and cerebrospinal fluid of patients with multiple sclerosis (MS). The fraction of IgG Ab as well as its Fab fragments and isolated light chains of both kappa- and lambda-types were shown to catalyze effectively the hydrolysis of DNA and RNA. It is shown by different methods that the capability for nucleic acid hydrolysis is an intrinsic property of the polyclonal Ab. NA-hydrolyzing Ab were detected in the blood of 69 of 72 and in the cerebrospinal fluid of 5 of 5 examined MS patients, while they were not detected in the blood of any of 50 healthy donors examined. Comparison of relative rates of RNA hydrolysis and of the substrate specificity in hydrolysis of various model RNAs--cCMP, poly(U), poly(A), and poly(C)--revealed pronounced differences of MS antibodies from ribonucleases of human blood, ribonuclease A, and all earlier described abzymes. The abzymes are usually characterized by relatively low specific activities in comparison with that of normal enzymes catalyzing analogous reactions. Ab from the blood of MS patients are the first example of autoabzymes whose specific activity in RNA hydrolysis is comparable or even higher than that of pancreatic ribonuclease A--one of the most active RNA-hydrolyzing enzymes.     

Bridging the gap between theory and practice: a supervision programme for nursing students

This paper describes nursing students' views of a supervision programme provided during the second semester of their education, which was their first period of nursing practice. A form with open questions and a 24-item questionnaire were completed by the 28 nursing students. The analysis of their responses was a combination of factor analysis and grounded theory approach, based on comparative analysis. The results indicate two specific effects of the programme: personal growth and integration of knowledge. The process of creating knowledge includes four stages: awareness of concepts and phenomena, development of a 'language of caring', development of a 'model' of communication, and reflection gained as an effect of the intervention. The nursing students reported that reflection was a way to bridge the gap between theory and practice. Their views of the effect of the supervision showed high values for the following three factors: improved interpersonal skills, improved professional skills, and improved communication skills.     

Analysis of the structure of cardiac rhythm during treatment of auricular fibrillation with digitalis

The structure of cardiac rhythm was studied with the help of specialized computers during digitalization in 60 patients with atrial fibrillation of different etiology. The reduction of the heart contractions rate under digitalization is accompanied by certain changes in the structure of cardiac rhythm: the arrhythmic pattern of the ventricular contractions increases with a predominant growth of the number of long R--R intervals, the transitions from short intervals to longer ones become sharper, and portions of a relatively stable ventricular rhythm appear. Three main types of dynamics of the rhythm structure were distinguished on the basis of the changes in the interval R--R histogram. The described changes in the structure of cardiac rhythm are not specific, but when Digitalis drugs are used alone they can be used as additional criteria for digitalization.     

Metatarsus varus corrected by open wedge osteotomy of the first cuneiform bone

The persistence of metatarsus adductus varus has been a problem in management. We have treated a series of selected patients with this problem and believe that our results have been better than with the procedure we have used in the past. Fowler has described a procedure which seems ideal for the patients in our series. Through personal communication the procedure and its application were discussed and the series was started eight years ago. Our series is small because our patients are responding to other forms of treatment at an earlier age. The few that do not respond are now considered for the operation described. The procedure is relatively simple to perform. Full correction should be obtained at the time of surgery. Casting is utilized to hold the correction and immobilize the extremity for healing. Our unsatisfactory results occurred because of errors in technique or poor selection of patients. We believe that this procedure should be considered in the older patient with metatarsus varus.     

Optimization studies of CVD growth of GaAs0.6P0.4

CVD growth conditions, particularly growth temperature and partial pressures of the reactant gases, strongly affect the growth characteristics and properties of GaAs_0.6P_0.4 epitaxial layers grown on GaAs substrates. For LED’s the most important properties of the material are B/J (brightness per unit current density) and surface morphology. This paper presents the results of a systematic study of the effect of temperature and reactant gas partial pressure (at a fixed III/V ratio) on B/J, surface morphology, growth rate, impurity doping and layer composition. Growth conditions which yield the optimum properties for LED’s are determined. The results are interpreted on the basis of kinetic and thermodynamic mechanisms controlling the growth process under various growth conditions. At constant temperature and constant III/V ratio, increasing the partial pressures causes the growth process to change from mass transport limited, where the growth rate increases with increasing partial pressures, to kinetically limited, where the growth rate is independent of partial pressures. Good morphology layers are obtained over a range of partial pressures around the transition from mass transport limited to kinetically limited growth. The B/J peaks at a value of partial pressure in the kinetically limited regime at which good morphology layers are obtained. Although B/J increases with increasing growth rate in the mass transport regime, the maximum B/J occurs in the region where growth rate is independent of partial pressures so that growth rate alone is not sufficient to determine B/J. In contrast to the “parabolic≓ dependence of growth rate on growth temperature, caused by the transition from the mass transport regime to the kinetic regime, the relative incorporation of As, P, and Te varies with temperature in the manner predicted from thermodynamics in both regimes. This behavior is consistent with the growth rate in the kinetic regime being limited by the desorption of chlorine atoms from the growth surface, with the reaction of As, P, and Te with the Ga proceeding thermodynamically at all temperatures.     

Evolution of fuel nitrogen in coal devolatilization

The distribution of fuel nitrogen in the devolatilization products of a lignite and 12 bituminous coals has been observed experimentally. For these coals under isothermal conditions (300 < T < 1000 °Cand 5 < t < 80 s) the behaviour of the nitrogen evolution was found to be similar. Nitrogen which is initially released is contained almost entirely in the tar. The chemical composition, ¹³C-n.m.r. spectra and infrared spectra of the tars and parent coals are strikingly similar and it is reasonable to suspect that the tar nitrogen occurs in the same structures as in the parent coal. Secondary release of nitrogen into nontar volatiles occurs only at high temperature. Results can be described with first-order kinetics using the same rate constant for all the coals studied. Initial nitrogen release is described by the tar release rate constant, k = 81 exp (−5800/T) (s⁻¹), which is similar to the rate constant for initial nitrogen release measured by Pohl and Sarofim. Secondary release of nitrogen is described with a rate constant which is similar to the results measured by Blair, Wendt and Bartok. This rate is smaller than that measured for the decomposition of nitrogen-ring compounds such as pyridines or pyrroles. The results suggest that coal nitrogen is contained almost entirely in tightly bound rings which are released without breakage in the tar during the initial stage of devolatilization; the remainder is released at higher temperatures when rings are ruptured.     

The importance of dietary control in metabolic studies of manic-depressive patients

Diet control of electrolyte intake appears to diminish day to day variation of urinary electrolyte output. Urine sodium concentration is more affected by diet control than potassium, possibly due to the greater variation in sodium ingestion on uncontrolled diets. The coefficient of variation of urinary sodium excretion on the controlled diet was not significantly greater than the variation in sodium ingestion. These experimental results suggest that controlled diets reduce random variation in sodium and potassium excretion and therefore enhance the possibility of observing illness-related biological changes.