Personal respiratory protection against Mycobacterium tuberculosis

The present study investigated the simultaneous occurrence of emergent stimulus-response relations (functional equivalence) and stimulus-stimulus relations (stimulus equivalence). After being pretrained and tested on two symbolic match-to-sample tasks (X1-Y1, X2-Y2), 20 4- and 5-year-old children were trained to emit specified responses to pairs of stimuli (A1-R1, B1-R1, A2-R2, B2-R2) in one setting (original training) and to emit other responses to one member of each pair (A1-R3, A2-R4) in another setting (reassignment training). Of the 18 children who responded correctly on all trained tasks, 15 emitted the novel responses also in the presence of the nonreassigned stimuli (B1-R3, B2-R4). Eleven of these children also matched same-class stimuli with one another (A1-B1, A2-B2, and vice versa). Additional tests with four of these children documented the formation of conditional response-stimulus relations (R3-B1, R4-B2) in all four children, and of conditional response-response relations (R1-R3, R2-R4, and vice versa) in two of them. Children who did not show stimulus control transfer also failed to match same-class stimuli with one another. Present findings, together with those obtained in animal research, suggest that functional equivalence can imply but does not require stimulus equivalence.     

Long-term low-dose calcitriol treatment in predialysis chronic renal failure: can it prevent hyperparathyroid bone disease?

In an uncontrolled open study 13 patients with moderate to preterminal renal failure were treated with low doses (average 0.36 micrograms/day) of calcitriol up to the time of renal transplantation, which was performed before dialysis had been initiated. A transiliac bone biopsy was obtained both at the start and at the end of the treatment period, the latter coinciding with renal transplantation. All patients who started calcitriol treatment at a creatinine clearance (Ccr) above 30 ml/min had normal bone histology at the time of transplantation, but this was not observed when calcitriol treatment was started at Ccr below 30 ml/min. The study suggests that full benefit of calcitriol at the bone level is obtained only if prophylactic administration is started early in the course of renal failure.     

Minimal invasive therapy of aneurysms of the superficial femoral artery and the popliteal artery

Percutaneous stent placement has been described for treatment of aneurysms as an alternative to surgical therapy. Literature reports of percutaneous minimal invasive therapy of peripheral aneurysms shall be reviewed and compared with our own results. Six male patients (51-69 years) with femoropopliteal occlusions related to aneurysms were treated percutaneously. In two cases Wallstents and in four cases polyester-covered nitinol stents were applicated. A clinical investigation including doppler-ultrasound was performed 24 hrs, 1, 3, 6, 12 and 24 months after the intervention. Stent placement succeeded in all cases. No adjunctive surgical treatment was necessary. Ankle-brachial-index (ABI) improved from 0.22 +/- 0.2 before to 0.74 +/- 0.2 24 hours after the intervention. One patient was lost for follow-up (Wallstent). A decrease of ABI and additional intraarterial angiography revealed stent-graft occlusion within one month (n = 2) and within three months (n = 1). One of these cases was successfully recanalized with local fibrinolysis therapy. In three patients patency of the stent persisted for 24 (+/- 2) months follow-up with three-vessel-supply of the calf. These results warrant further investigations for this minimal invasive method of percutaneous stent deployment as an alternative to surgical bypass treatment of femoropopliteal aneurysms. Time of hospitalization was reduced. At this time, surgical treatment of peripheral vascular aneurysms is gold standard.     

Tyrosine kinase inhibition produces specific alterations in axon guidance in the grasshopper embryo

Tyrosine kinase signaling pathways are essential for process outgrowth and guidance during nervous system development. We have examined the roles of tyrosine kinase activity in programming growth cone guidance decisions in an intact nervous system in which neurons can be individually identified. We applied the tyrosine kinase inhibitors herbimycin A and genistein to whole 40% grasshopper embryos placed in medium, or injected the inhibitors into intact grasshopper eggs. Both inhibitors caused interneuronal axons that normally would grow along the longitudinal connectives to instead leave the central nervous system (CNS) within the segmental nerve root and grow out toward the body wall muscles. In addition, herbimycin A produced pathfinding errors in which many longitudinal axons crossed the CNS midline. To study how this drug affected guidance decisions made by individual growth cones, we dye-filled the pCC interneuron, which normally extends an axon anteriorly along the ipsilateral longitudinal connective. In the presence of herbimycin A, the pCC growth cone was redirected across the anterior commissure. These phenotypes suggest that tyrosine kinase inhibition blocks a signaling mechanism that repels the growth cones of longitudinal connective neurons and prevents them from crossing the midline.     

Properties of whole saliva and dental plaque in relation to 40-month consumption of chewing gums containing xylitol, sorbitol of sucrose

The concern with nursing research in the future work of nurse graduates. Expectations from the viewpoint of the nurse researcher. Keeping in mind the concerns which occupy nurse researchers now and in the future, expectations are raised of the graduates of degree programmes in nursing science which are now also being established in the Federal Republic of Germany. This takes into account the structurally determined areas of self determined action in new fields of professional practice. Nurse graduates will be seen as "change agents" in their future areas of work and will have three essential aspects of involvement with nursing research: 1. they themselves will conduct research 2. they will receive, put into practice and transmit results of nursing research 3. they will initiate and commission nursing research projects. According to the broad topics of nursing research, requirements for nurses to act as professionals in their new working fields are formulated referring to the given structural conditions in Germany.     

Glu227-->Lys substitution in the acidic loop of major histocompatibility complex class I alpha 3 domain distinguishes low avidity CD8 coreceptor and avidity-enhanced CD8 accessory functions

Cytotoxic T lymphocyte (CTL) activation requires specific T cell receptor (TCR)-class I major histocompatibility complex (MHC) antigen complex interactions as well as the participation of coreceptor or accessory molecules on the surface of CTL. CD8 can serve as a coreceptor in that it binds to the same MHC class I molecules as the TCR to facilitate efficient TCR signaling. In addition, CD8 can be "activated" by TCR stimulation to bind to class I molecules with high avidity, including class I not recognized by the TCR as antigenic complexes (non-antigen [Ag] class I), to augment CTL responses and thus serve an accessory molecule function. A Glu/Asp227-->Lys substitution in the class I alpha 3 domain acidic loop abrogates lysis of target cells expressing these mutant molecules by alloreactive CD8-dependent CTL. Lack of response is attributed to the destruction of the CD8 binding site in the alpha 3 domain which is likely to disrupt CD8 coreceptor function. The relative importance of the class I alpha 3 domain acidic loop Glu227 in coreceptor as opposed to accessory functions of CD8 is unclear. To address this issue, we examined CTL adhesion and degranulation in response to immobilized class I-peptide complexes formed in vitro from antigenic peptides and purified class I molecules containing wild-type or Glu227-->Lys substituted alpha 3 domains. The alpha 3 domain mutant class I-peptide complexes were bound by CTL and triggered degranulation, however to much lower levels than wild-type class I-peptide complexes. In further experiments, it is directly demonstrated that the alpha 3 domain mutant class I molecules, which lack the Glu227 CD8 binding site, still serve as TCR-activated, avidity-enhanced CD8 accessory ligands. However, mutant class I peptide Ag complexes failed to effectively serve as CD8 coreceptor ligands to initiate TCR-dependent signals required to induce avidity-enhanced CD8 binding to coimmobilized non-Ag class I molecules. Thus the Glu227-->Lys mutation effectively distinguishes CD8 coreceptor and avidity-enhanced CD8 accessory functions.     

An index for paresis and defective healing--an easily applied method for objectively determining therapeutic results in facial paresis (author's transl)

Residuals of facial paralysis consist of a great variety of cosmetic and functional anomalies which differ in quality and/or quantity. An internationally standardized evaluation of such defects is mandatory for the assessment of the results of different therapeutic procedures. In the present study, a system has been developed to record the results of facial paralysis following therapy. Such a system does not require specialized training, instrumentation or require significant time for completion. A clearly-defined "Yes-No" evaluation criteria is established which creates a high interscorer reliability. The usefulness of this scoring system was tested by three examiners on 42 patients following facial nerve surgery, with an obtained interscorer reliability of 93%.     

Immunology and adjuvant chemoimmunotherapy of breast cancer

Antibody against a breast carcinoma antigen was present in patients with breast carcinoma and other cancer more often (P less than .05) than in normal women. The incidence of antibody in women with breast carcinoma correlated with the presence or absence of gross tumor, and the titer of antibody paralleled the clinical course. These results suggest importance of a host-immune response to breast carcinoma. Fifty-seven patients with stage II carcinoma of the breast were entered into a prospective randomized adjuvant chemoimmunotherapy program of cyclophosphamide, methotrexate, and fluorouracil, and BCG vaccine +/- an irradiated allogeneic tumor cell vaccine. After 24 months of study, metastases occurred in two patients (3.5%) and a new primary carcinoma developed in the contralateral breast in two others, for an overall treatment failure rate of 7%. Adjuvant chemoimmunotherapy can delay early recurrence. Long-term follow-up is needed to assess the significance of these results.     

Antisense oligonucleotide inhibition of hepatitis C virus gene expression in transformed hepatocytes

Genetic and biochemical studies have provided convincing evidence that the 5' noncoding region (5' NCR) of hepatitis C virus (HCV) is highly conserved among viral isolates worldwide and that translation of HCV is directed by an internal ribosome entry site (IRES) located within the 5' NCR. We have investigated inhibition of HCV gene expression using antisense oligonucleotides complementary to the 5' NCR, translation initiation codon, and core protein coding sequences. Oligonucleotides were evaluated for activity after treatment of a human hepatocyte cell line expressing the HCV 5' NCR, core protein coding sequences, and the majority of the envelope gene (E1). More than 50 oligonucleotides were evaluated for inhibition of HCV RNA and protein expression. Two oligonucleotides, ISIS 6095, targeted to a stem-loop structure within the 5' NCR known to be important for IRES function, and ISIS 6547, targeted to sequences spanning the AUG used for initiation of HCV polyprotein translation, were found to be the most effective at inhibiting HCV gene expression. ISIS 6095 and 6547 caused concentration-dependent reductions in HCV RNA and protein levels, with 50% inhibitory concentrations of 0.1 to 0.2 microM. Reduction of RNA levels, and subsequently protein levels, by these phosphorothioate oligonucleotides was consistent with RNase H cleavage of RNA at the site of oligonucleotide hybridization. Chemically modified HCV antisense phosphodiester oligonucleotides were designed and evaluated for inhibition of core protein expression to identify oligonucleotides and HCV target sequences that do not require RNase H activity to inhibit expression. A uniformly modified 2'-methoxyethoxy phosphodiester antisense oligonucleotide complementary to the initiator AUG reduced HCV core protein levels as effectively as phosphorothioate oligonucleotide ISIS 6095 but without reducing HCV RNA levels. Results of our studies show that HCV gene expression is reduced by antisense oligonucleotides and demonstrate that it is feasible to design antisense oligonucleotide inhibitors of translation that do not require RNase H activation. The data demonstrate that chemically modified antisense oligonucleotides can be used as tools to identify important regulatory sequences and/or structures important for efficient translation of HCV.