Vitamin D3 inhibits proliferation and increases c-myc expression in fibroblasts from psoriatic patients

Fibroblast cultures were established from the skin of normal and psoriatic subjects. The response to 1 alpha,25-dihydroxyvitamin D3 [1,25-(OH)2D3] of each kind of cells was assessed by measuring tritiated thymidine incorporation into DNA as an index of cell proliferation. We found that both types of cells responded with a similar dose- and time-dependent inhibition of thymidine incorporation. We also studied the response of the mRNA encoding the proto-oncogene c-myc, since its level is associated to the proliferative state in many cell types. Psoriatic fibroblasts contained higher basal amounts of c-myc RNA than control fibroblasts. Addition of 1,25-(OH)2D3 to the culture medium induced a time-dependent increase of c-myc RNA in psoriatic fibroblasts but not in controls. As a control, retinoic acid had no effect in any of the two cell types. It is concluded that in primary normal human fibroblasts, c-myc RNA levels are not correlated with the proliferative state, and that there is an altered expression of this proto-oncogene in psoriasis.     

Prognostic factors in muscle-invasive bladder cancer treated with radiotherapy: an immunohistochemical study

OBJECTIVE: To determine the prognostic role of p53, Ki-67 and p21 for patients with muscle-invasive bladder cancer treated with curative intent by radiotherapy. PATIENTS AND METHODS: The study included 131 patients (24 women and 107 men, median age 72 years, range 40-86) with transitional cell carcinoma (T2-T4) treated with external definitive pelvic radiotherapy between 1985 and 1994. Paraffin-embedded pretreatment biopsies from the patients were examined for the presence of p53, p21 and Ki-67, detected by immunohistochemistry, and related to tumour stage, grade and patient survival. RESULTS: The expression of p53 protein correlated positively with the detection of Ki-67 (P < 0.05) but did not correlate with p21. None of the immunohistochemical variables (p53, p21 or Ki-67) correlated with T category and only Ki-67 correlated with histological grade. Patients with > 5% p21 expression tended to live longer than those with < 5% (P = 0.09). In a multivariate analysis, the T category (T2/T3 vs. T4), histological grade (2 vs. 3) and p21 expression (< or = 5% vs. > 5%) were independent prognostic factors for overall survival. CONCLUSION: Further investigation is warranted in patients with muscle-invasive bladder cancer undergoing different types of treatment p21 seems to play an independent prognostic role in these patients, in addition to T category and grade.     

Collective memories of Germans and Japanese about the past half-century

We investigate the collective memories of two samples drawn in 1991, one from the former West Germany and one from Yokohama, Japan. In the early 1990s such samples included many members of World War II cohorts and also cohorts born long after that war had ended. We consider the relation of age, conceptualised as birth cohort, to the salience of memories of national and world events that were mentioned as important in response to a quite general open-ended question about the past half-century. The relations are similar across the two countries in so far as external events like World War II might have had similar impacts on each population, while each country is distinctive with regard to events that especially impinged upon it. Hypotheses about the importance of adolescence and early adulthood to the imprinting of memories are generally confirmed, but several types of evidence suggest the need to extend the delimiting ages to earlier than the mid-teens and later than the mid-twenties. Other evidence indicates the desirability of distinguishing between recent events that are the focus of media attention and earlier events that depend more fully on autobiographical memory.     

Influence of gas composition on recurrence of atelectasis after a reexpansion maneuver during general anesthesia

BACKGROUND: Atelectasis, an important cause of impaired gas exchange during general anesthesia, may be eliminated by a vital capacity maneuver. However, it is not clear whether such a maneuver will have a sustained effect. The aim of this study was to determine the impact of gas composition on reappearance of atelectasis and impairment of gas exchange after a vital capacity maneuver. METHODS: A consecutive sample of 12 adults with healthy lungs who were scheduled for elective surgery were studied. Thirty minutes after induction of anesthesia with fentanyl and propofol, the lungs were hyperinflated manually up to an airway pressure of 40 cmH2O. FIO2 was either kept at 0.4 (group 1, n = 6) or changed to 1.0 (group 2, n = 6) during the recruitment maneuver. Atelectasis was assessed by computed tomography. The amount of dense areas was measured at end-expiration in a transverse plane at the base of the lungs. The ventilation-perfusion distributions (VA/Q) were estimated with the multiple inert gas elimination technique. The static compliance of the total respiratory system (Crs) was measured with the flow interruption technique. RESULTS: In group 1 (FIO2 = 0.4), the recruitment maneuver virtually eliminated atelectasis for at least 40 min, reduced shunt (VA/Q < 0.005), and increased at the same time the relative perfusion to poorly ventilated lung units (0.005 < VA/Q < 0.1; mean values are given). The arterial oxygen tension (PaO2) increased from 137 mmHg (18.3 kPa) to 163 mmHg (21.7 kPa; before and 40 min after recruitment, respectively; P = 0.028). In contrast to these findings, atelectasis recurred within 5 min after recruitment in group 2 (FIO2 = 1.0). Comparing the values before and 40 min after recruitment, all parameters of VA/Q were unchanged. In both groups, Crs increased from 57.1/55.0 ml.cmH2O-1 (group 1/group 2) before to 70.1/67.4 ml.cmH2O-1 after the recruitment maneuver. Crs showed a slow decrease thereafter (40 min after recruitment: 61.4/60.0 ml.cmH2O-1), with no difference between the two groups. CONCLUSIONS: The composition of inspiratory gas plays an important role in the recurrence of collapse of previously reexpanded atelectatic lung tissue during general anesthesia in patients with healthy lungs. The reason for the instability of these lung units remains to be established. The change in the amount of atelectasis and shunt appears to be independent of the change in the compliance of the respiratory system.     

Biapenem versus imipenem/cilastatin in the treatment of complicated intra-abdominal infections: report from a Swedish Study Group

The objective of this study is to describe usual medical management and costs associated with recurrent respiratory infections in subjects with chronic obstructive bronchitis in France. A prospective survey was performed in Autumn 1994 on a national sample of private practice pulmonologists (N = 71). Two hundred forty-four patients, presenting at least one infection of the lower respiratory tract, were included. Bronchitis was the most frequent acute exacerbation observed (94%). Pneumonia concerned 9% of the patients. Biological tests, X-rays and pulmonary function tests were prescribed for, respectively, 59, 65 and 45% of the patients. Following the visit, 15 patients were hospitalized (6%). The direct medical cost per acute exacerbation was estimated 3,289 francs (1994 value) of which 60% were hospital-related. An average 10.4 day sick-leave was prescribed to 21% of patients in employment. For those patients, this sick-leave was associated to an extra-cost of 1,264-1,876 francs for Social Security and of 0-2,553 francs out of pocket per episode varying according to their Benefit Regimen.     

The prospects for using the genetically engineered surface antigen of the hepatitis B virus (HBsAg) expressed by recombinant poxvirus strains as the basis for vaccines against hepatitis B

The use of a recombinant poxvirus (RPV) strain, expressing HBsAg in the process of reproduction in different bioreactor systems under stationary and bioreactor conditions of cultivation, made it possible to obtain highly purified HBsAg. The identity and purity of HBsAg was confirmed by the analysis of its amino acid composition, SDS electrophoresis in polyacrylamide gel, electron microscopy and high-performance liquid chromatography. Good prospects of the use of RPV-expressed gene engineering HBsAg as the basis vaccines against hepatitis B was demonstrated in 10 experimental batches of vaccine. All batches of the preparation had pronounced immunogenicity and were safe and nontoxic in animal experiments. The ID50 of experimental batches did not exceed 211 ng/ml, which, according to the data of comparative experiments, was lower than, or equal to, corresponding values of analogous foreign commercial preparations, based on plasma or yeast HBsAg.     

Effect of caffeine and reduced temperature (20 degrees C) on the organization of the pre-Golgi and the Golgi stack membranes

In the present study we have dissected the transport pathways between the ER and the Golgi complex using a recently introduced (Kuismanen, E., J. J?ntti, V. M?kiranta, and M. Sariola. 1992. J. Cell Sci. 102:505-513) inhibition of transport by caffeine at 20 degrees C. Recovery of the Golgi complex from brefeldin A (BFA) treatment was inhibited by caffeine at reduced temperature (20 degrees C) suggesting that caffeine inhibits the membrane traffic between the ER and the Golgi complex. Caffeine at 20 degrees C did not inhibit the BFA-induced retrograde movement of the Golgi membranes. Further, incubation of the cells in 10 mM caffeine at 20 degrees C had profound effects on the distribution and the organization of the pre-Golgi and the Golgi stack membranes. Caffeine treatment at 20 degrees C resulted in a selective and reversible translocation of the pre- and cis-Golgi marker protein (p58) to the periphery of the cell. This caffeine-induced effect on the Golgi complex was different from that induced by BFA, since mannosidase II, a Golgi stack marker, remained perinuclearly located and the Golgi stack coat protein, beta-COP, was not detached from Golgi membranes in the presence of 10 mM caffeine at 20 degrees C. Electron microscopic analysis showed that, in the presence of caffeine at 20 degrees C, the morphology of the Golgi stack was altered and accumulation of numerous small vesicles in the Golgi region was observed. The results in the present study suggest that caffeine at reduced temperature (20 degrees C) reveals a functional interface between the pre-Golgi and the Golgi stack.     

Structures of sialylated oligosaccharides of human erythropoietin expressed in recombinant BHK-21 cells

The native structures of the Asn-linked oligosaccharides and the O-glycans at Ser126 of human erythropoietin expressed from recombinant BHK cells have been elucidated. Enzymatically released N-glycans were studied by methylation analyses, fast-atom-bombardment mass spectrometry as well as one- and two-dimensional 1H-NMR spectrometry at 600 MHz. Many (82.7%) were found to be tetraantennary N-acetyllactosamine-type (22.8% with one, 3.6% with two and 0.4% with three N-acetyllactosamine repeats) being tetrasialylated (41%), trisialylated (29.6%) and disialylated (12.2%). A few (9.7%; 4.1% 2,4-branched, 5.6%, 2,6-branched) of the chains were triantennary (5.4% trisialyl, 4.3% disialyl) and 4.6% were of the disialyl diantennary type. Almost all of the innermost GlcNAc residues were alpha 1-6 fucosylated and NeuAc was exclusively alpha 2-3 linked to Gal beta 1-4GlcNAc-R; 60% of the protein was found to be O-glycosylated at Ser126; structures were monosialylated (70%) or disialylated (30%) forms of the Gal beta 1-3GalNAc core type. Glycosylation patterns at individual Asn-Xaa-Thr/Ser sites were determined by analytical high-pH anion-exchange chromatography with pulsed amperometric detection. Only tetraantennary chains with 0-3 N-acetyllactosamine repeats were detected at Asn38 and Asn83, while almost all of the di- and triantennary oligosaccharides were attached to Asn24. Batch analysis of different preparations of recombinant erythropoietin revealed the high reproducibility of the production procedure. Structures containing terminal GalNAc-GlcNAc were detected in small amounts in a few batches.