Changes of epidermal cell morphology and keratin expression induced by inhibitors of protein kinase C.

Several lines of evidence show protein kinase C as being involved in various regulatory processes in keratinocyte biology, e.g. proliferation and differentiation. In the present study, we investigated the effects of three different inhibitors of protein kinase C, staurosporine, CP 46'665-1, and tiflucarbine, on cell morphology and keratin expression in a non-tumorigenic human keratinocyte cell line (HaCaT cells). Staurosporine, being the most potent inhibitor of protein kinase C activity in vitro, and CP 46'665-1 induced morphological transformation to a fibroblast-like cell shape. In contrast, no changes in cell morphology were observed after exposure to tiflucarbine. The investigation of keratin expression in HaCaT cells grown in the presence of the different compounds revealed the following changes: After 72 h of cultivation, keratins 8 and 18 were still expressed in treated cells, whereas expression of keratin 13 was decreased as compared to control cells. Immunoblotting to detect vimentin demonstrated its absence in treated and control cells. Since tiflucarbine is known as a dual protein kinase C/calmodulin inhibitor whereas staurosporine and CP 46'665-1 do not antagonize calmodulin function, it might be possible that not only protein kinase C but also calmodulin is involved in the process leading to the morphological changes.     

Radiographic prediction of failure after fixation of cervical hip fracture

During 1984-1985, 410 patients with cervical hip fracture were randomized between 2 methods of internal fixation-a single nail (Rydell) or 2 LIH hook pins (LIH). The patients were followed-up prospectively for at least 2 years. Radiographs were taken after 1 week, 1, 3, 6, 12, and 24 months. The radiographs of the 295 paients alive 2 years postoperatively were examined by one of the authors. The sliding and the diversion of the pins and the nail in the anteroposterior projection and the diversion in the lateral projection were measured. In the failure group (non-union, late segmental collapse), the greatest sliding was noted within 1 month postoperatively and the diversion increased up to 3 months. Significant differences between the failure and the non-failure groups could be seen even after 1 week. We also found that the degree of sliding of the LIH pins and the Rydell nail 1 month postoperatively is comparable to the scintigraphic pattern 2 weeks postoperatively in predicting failure after nternal fixation of cervical hip fractures.     

The detection of internal mammary lymph nodal chain metastases in breast cancer using radiolabelled colloids

The authors report their studies of 39 lymphoscintigraphies performed on patients with breast cancer. They point out that interpretation of scintigraphic imaging must take into account the morphologic variations of the lymph nodes of the internal mammary chains (i.e. single central chain, single central lymph node) and the morphological difference in the symmetry of lymph nodes considered non-pathologic to avoid false positives. The authors retain that lack of visualization of a chain, conspicuous increase in size of a lymph node, asymmetry of pathologic development, or reduced uptake by one or more lymph nodes of the internal mammary chains must be interpreted as a sign of metastatic spread. The authors recommend lymphoscintigraphy as an effective technique in the screening of breast cancer patients for staging, follow-up, restaging, and planning of radiotherapy.     

Candidate genes associated with ageing and life expectancy in the Jerusalem longitudinal study

In an exploratory study, 11 common polymorphisms were examined for contributing to longevity including: apolipoprotein E (apoE), methylenetetrahydrofolate reductase (MTHFR), cathepsin D (CAD), superoxide dismutase 2 (SOD2), angiotensinogen (AGT) and insulin-like growth factor 2 (IGF2), Leiden factor 7, p53 oncogene, dopamine D4 receptor (DRD4) and the serotonin transporter (SERT). Genotype and allele frequencies of these genes were compared in 224 older (75 years) Jewish Jerusalem residents of Ashkenazi ethnicity to a group of 441 younger subjects (22 years). Nominally significant results provide suggestive evidence in the Ashkenazi group that apoE, MHTFR, SOD2, IGF2 ApaI, and factor VII are risk factors for a single outcome, survival to 75. Overall, the more genetically homogenous Ashkenazi ethnic group showed evidence for association in five genes examined suggesting that future studies in this population would gainfully focus on this ethnic group.     

Proliferation and production of hemopoietic cells in two stages of disease: Preleukemia and overt leukemia

Summary The kinetics of erythropoietic and granulocytopoietic cell proliferation have been investigated in the same patient at two distinct stages: firstly in preleukemia presenting as pancytopenia with ineffective erythropoiesis, and secondly 2 years later in acute myelogenous leukemia. The method of investigation is based on determining the DNA synthesis rate of individual cells by means of quantitative¹⁴C-autoradiography after short-term incubation with¹⁴C-thymidine and fluorodeoxyuridine.Erythropoiesis was equally ineffective in the two stages, the rate of proliferation, however, slowed down towards the leukemic state. The production rate of myeloblasts was markedly reduced in preleukemia accompanied by a very low labelling index. In leukemia on the other hand the production rate was increased to such a degree that the leukemic myeoblast compartment is to be considered as prevailingly self-reproductive. The proliferation rate of myeloblasts was reduced already in preleukemia, and there was a further decrease in leukemia. From the point of view of cell kinetics the manifestation of leukemia in this patient is explained best by a change in the mode of proliferation: the myeloblasts change from steady state growth to behaving like an exponentially expanding population.Study performed under the association contract for hematology between EURATOM and GSF no. 089-72-I-BIAD Supported by the Deutsche Forschungsgemeinschaft: SFB 51/E-3     

Antigenic and molecular analyses of different Chlamydia pneumoniae strains.

Chlamydia pneumoniae is an important human respiratory pathogen. Classification of C. pneumoniae isolates into distinguishable serovars or genotypes has not yet been reported. To determine whether antigenic or molecular variants among C. pneumoniae isolates exist, six strains were studied via immunoblot analysis and DNA sequence determination of the entire major outer membrane protein (MOMP) gene omp1. The strains included four prototype strains and two clinical isolates from our laboratory. Immunoblot analysis of sera from patients infected with C. pneumoniae revealed antigenic differences between the C. pneumoniae strains. Strong reactivity of one serum sample with a 65-kDa protein in two C. pneumoniae strains which was not observed with the other strains was the most prominent finding. All sera reacted with the 40-kDa MOMP. Comparison of the omp1 DNA sequences revealed that the omp1 genes of all strains were identical and were 100% identical to the sequence of the omp1 gene of C. pneumoniae AR-39. The results of this study demonstrate that unlike C. trachomatis, the omp1 gene is conserved in C. pneumoniae. Furthermore, it was shown that C. pneumoniae strains are antigenically different. This finding indicates that more than one serovar of C. pneumoniae exist.     

Monosomy and trisomy of 15q24→qter in a family with a translocation t(6;15)(P25;q24)

A child with multiple anomalies, including growth retardation, a left-sided diaphragmatic hernia with lung hypoplasia, and cerebral malformations is described. Cytogenetic investigation demonstrated a deletion of the distal part of one chromosome 15, del(15)(q24qter), an aberration not previously described. Family studies revealed that the mother had a balanced translocation, t(6;15)(p25;q24). Two of her subsequent pregnancies resulted in abortions after prenatal diagnosis: one fetus was trisomic for 15q24→qter, while the other had monosomy 15q24→qter and a left-sided diaphragmatic hernia similar to the first child.     

IR-und UV-spektroskopische Eigenschaften einer homologen Reihe von molekulareinheitlichen, 12gliedrige Ringe enthaltenden Leiteroligomeren

The reactions of multiple acrylates of oligo[(hydroxyphenylene)methylene] s ( 2a–2f ), strongly diluted in boiling benzene, with 2,2′-azoisobutyronitrile in a mole ratio of 1:10, were investigated. The elemental analysis and the determination of relative molar masses of the resulting products ( 3, 4, 5, 6a, 6b, 7a and 7b ) demonstrate that their molecules contain two nitrile groups. These data, together with the IR and UV spectra, show that the products are molecularly uniform ladder oligomers with two 1-cyano-1-methylethyl groups on both ends.