Distribution of CNTF receptor alpha protein in the central nervous system of the chick embryo

Ciliary neurotrophic factor (CNTF) promotes the survival and differentiation of various neuronal and glial cell populations in the nervous system of vertebrates. In mammals, the ligand-binding alpha-subunit of the CNTF receptor (CNTFRalpha) is expressed in a variety of neuronal populations, including all CNTF-responsive cells. Previous studies suggested that functional differences in the CNTF/CNTF receptor system between chicks and mammals exist. The purpose of the present study was to examine the temporal and spatial expression pattern of the chick CNTFRalpha protein during CNS development. Receptor expression was detectable by immunoblotting in all CNS areas tested but showed area-specific developmental regulation. Interestingly, two variants of CNTFRalpha, 69 and 65 kD, were identified by immunoblotting with a shift from the higher to the lower molecular mass species occurring during development. Immunoreactivity for CNTFRalpha protein was preferentially observed in neuropil and white matter structures of the developing CNS while neuronal somata generally appeared unlabeled. For example, expression was observed in the olfactory system, in the telencephalon, in parts of the somatosensory system, in components of the tectofugal pathway, in the cerebellum, and in auditory brainstem nuclei. Fiber tracts that exhibit CNTFRalpha immunoreactivity were the lateral forebrain bundle, occipitomesencephalic tract, quintofrontal tract, and vestibular nerve. Our study identifies potential new targets of a chick CNTF-related molecule and reveals significant regional differences of CNTFRalpha protein expression between chick and mammals. These results suggest that the CNTF receptor performs distinct developmental functions in different animals.     

Dr. Elisabeth Hecker (1895-1986): career in child and adolescent psychiatry on the one hand--involvement in elimination of the handicapped on the other hand

During the period of national socialism in Loben/Lublinitz (Silesia) existed a children's special department, where many disabled and mentally retarded children were killed. This was happened under participation of the physician Elisabeth Hecker, who was one of the pioneer's of child and adolescent psychiatry in Germany. During the Second World War she was director of the Loben's clinic for adolescent psychiatry--one of the first of its sort and situated directly in the neighbourhood of the children's special department. Hecker announced children with negative ratings to the "Reich Committee for the Scientific Registration of Severe Genetically and Constitutionally Determined Diseases" in Berlin and transferred them to the children's special department in Loben. In 1979 the German Association of Child and Adolescent Psychiatry appointed Hecker as a honorary member for her commitment after the war. This honorary membership has been discussed critically because of her activities during the period of national socialism. The following paper analyses Hecker's involvement to the child "euthanasia" program based on unnoticed archival sources.     

Antimicrobial efficacy of semiconductor laser irradiation on implant surfaces

PURPOSE: This study was conducted to investigate the antimicrobial effect of an 809-nm semiconductor laser on common dental implant surfaces. MATERIALS AND METHODS: Sandblasted and acid-etched (SA), plasma-sprayed (TPS), and hydroxyapatite-coated (HA) titanium disks were incubated with a suspension of S. sanguinis (ATCC 10556) and subsequently irradiated with a gallium-aluminum-arsenide (GaAlAs) laser using a 600-microm optical fiber with a power output of 0.5 to 2.5 W, corresponding to power densities of 176.9 to 884.6 W/cm2. Bacterial reduction was calculated by counting colony-forming units on blood agar plates. Cell numbers were compared to untreated control samples and to samples treated with chlorhexidine digluconate (CHX). Heat development during irradiation of the implants placed in bone blocks was visualized by means of shortwave thermography. RESULTS: In TPS and SA specimens, laser irradiation led to a significant bacterial reduction at all power settings. In an energy-dependent manner, the number of viable bacteria was reduced by 45.0% to 99.4% in TPS specimens and 57.6% to 99.9% in SA specimens. On HA-coated disks, a significant bacterial kill was achieved at 2.0 W (98.2%) and 2.5 W (99.3%) only (t test, P < .05). For specimens treated with CHX, the bacterial counts were reduced by 99.99% in TPS and HA-coated samples and by 99.89% in SA samples. DISCUSSION: The results of the study indicate that the 809-nm semiconductor laser is capable of decontaminating implant surfaces. Surface characteristics determine the necessary power density to achieve a sufficient bactericidal effect. The bactericidal effect, however, was lower than that achieved by a 1-minute treatment with 0.2% CHX. The rapid heat generation during laser irradiation requires special consideration of thermal damage to adjacent tissues. CONCLUSION: No obvious advantage of semiconductor laser treatment over conventional methods of disinfection could be detected in vitro.     

Dimensional changes of one-piece frameworks cast from titanium,base metal,or noble metal alloys and supported on telescopic crowns

STATEMENT OF PROBLEM: The dimensional accuracy of 1-piece frameworks cast from commercially pure titanium and used to accommodate supporting telescopic crowns has not been demonstrated. PURPOSE: To compare dimensional changes incurred in frameworks cast from commercially pure titanium, a cobalt-chromium alloy, and a noble metal (gold) alloy. MATERIAL AND METHODS: This study was based on 2 different models, both prepared to receive telescopic crowns: 1 with 4 dies, designed to measure dimensional changes of the castings in the horizontal plane; and another with 2 dies, designed to measure dimensional changes in the vertical plane. As variables for the 2-die models, the palatal shape (16- and 20-mm radius) as well as the palatal depth (20-mm radius with the smallest palatal depth of 8 mm, 16-mm radius with flat palate and palatal depth of 10 mm, 16-mm radius with greatest palatal depth of 16 mm) were studied. Ten specimens each were fabricated from a commercially pure titanium, a cobalt-chromium alloy, and a gold alloy. All castings were fabricated under standardized conditions. All measurements were taken with a computer-controlled measuring microscope at the margins of the simulated telescopic crowns; these served to calculate the ideal midpoint from which the distances between the telescopic crowns were measured. The positional relation of the telescopic crowns was determined in horizontal and vertical directions. The measurements of the cast models were compared with measurements of the original model. The distances between the dies and the angles of the chosen telescopic crowns were calculated in fractions of millimeters and the angles were measured in degrees. The Kruskal-Wallis test and the Mann-Whitney U test were used for statistical analysis. The level of significance was alpha=5%. RESULTS: With the following exceptions, none of the 3 alloy types showed significantly different results. With the 4-die model, all 3 alloys showed significant variations from the original model for chosen lengths (P=.001). For those lengths, the dimensional accuracy of the noble metal alloy was approximately 99.9% of the length of the original; for the 2 other alloys, an average value of 99.4% was determined. With the 2-die models the calculated angle was significantly different from the original model for all alloys (P=.001 or.000), independent from the palatal vault and depth. Significant differences from the original model were also found for the distance between the 2 telescopic crowns with all alloys for the 2-die model with a 16-mm depth palatal vault and a 16-mm radius (P=.001,.006, or.009). CONCLUSIONS: Within the limitations of this study, the significant different dimensional changes both for the 4-die models and the 2-die models did not depend on the type of alloy. The 2-die models demonstrated significant dimensional changes resulting from the palatal geometry of the corresponding test models; the 4-die models demonstrated a tendency to contract toward the geometric center.     

Cytotoxic perforin+ and TIA-1+ infiltrates are associated with cell adhesion molecule expression in dilated cardiomyopathy

OBJECTIVE: To phenotypically characterize cytotoxic T-lymphocytes (CTLs: Perforin+ and TIA-1+ phenotypes) and to study the interactions with cell adhesion molecules (CAMs) in dilated cardiomyopathy (DCM). BACKGROUND: DCM is linked to intramyocardial inflammation, being characterized by T-lymphocytic infiltration and CAMs abundance. However, the pathogenic significance of increased CD3+ lymphocytes remains obscure as these do not correlate with CTLs (perforin+ and TIA1+ phenotypes). CAMs participate in the phenotypic repertoire and effector pathways of CTLs. METHODS: CAMs-expression (ICAM-1, VCAM-1, LFA-3, CD29, CD62E and CD62P and beta(2)-integrins), CD3+ (T-lymphocytes), CD57+ (NK-cells) and adhesion related (CD18+, CD11a+, CD11b+, CDw49d+) phenotyped infiltrates were investigated in endomyocardial biopsies (EMBs) from 89 DCM patients (33 female; LVEF<40%) using immunohistochemisty. The enteroviral genome was identified by nested RT-PCR. RESULTS: CAMs abundance was confirmed in 55 DCM patients (62%) and 29 EMBs (33%) were graded CTLs+ (>1.5 TIA-1+ and/or >2.0 perforin+ infiltrates/hpf). CTLs correlated with all endothelial CAMs-markers studied (P<0.01), the adhesion related phenotypes of infiltrates (LFA-1, VLA-4, CD18) and CD57+ NK-cells (P<0.02). There was no correlation of CTLs with CD3+ T-lymphocytes, CD11b+ macrophages, enteroviral infection (present in n=16/18%), clinical history and LVEF (P>0.05). Phenomena suggestive of CTLs mediated myocytolysis were observed in 10 patients (11%). CONCLUSIONS: CTLs-infiltrates are associated with endothelial CAMs-abundance and co-express adhesion related (beta2-integrins, VLA-4) and NK-cellular antigens (CD57) in DCM. Endothelial CAMs expression also reflects cytotoxic activation of intramyocardial infiltrates, which is not reflected by immunologically nai;ve CD3 T-lymphocytes.     

Early improvement under mirtazapine and paroxetine predicts later stable response and remission with high sensitivity in patients with major depression

OBJECTIVE: Current clinical knowledge holds that antidepressants have a delayed onset of efficacy. However, the delayed onset hypothesis has been questioned recently by survival analytical approaches. We aimed to test whether early improvement under antidepressant treatment is a clinically useful predictor of later stable response and remission. METHOD: We analyzed data from a randomized double-blind controlled trial with mirtazapine and paroxetine in patients with major depression (DSM-IV). Improvement was defined as a 17-item Hamilton Rating Scale for Depression (HAM-D-17) score reduction of > or = 20%. Stable response was defined as > or = 50% HAM-D-17 score reduction at week 4 and week 6, and stable remission as a HAM-D-17 score of < or = 7 at week 4 and week 6. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. RESULTS: Improvement occurred in a majority of the analyzed patients within 2 weeks (mirtazapine: 72.7% of 109 patients; paroxetine: 64.9% of 103 patients). Early improvement was a highly sensitive predictor of later stable response or stable remission for both drugs. NPV approached maximum values as early as week 2 for mirtazapine and week 3 for paroxetine. After 2 weeks of treatment with mirtazapine and 3 weeks with paroxetine, almost none of the patients who had not yet improved became a stable responder or stable remitter in the later course. CONCLUSION: Our results strongly suggest that early improvement predicts later stable response with high sensitivity. These empirically derived data question the delayed onset hypothesis for both antidepressants tested and provide important clinical clues for an individually tailored antidepressant treatment.     

Patient satisfaction with the outcome of surgery for urethral stricture

PURPOSE: We assessed patient satisfaction with the outcome of surgery for urethral strictures and compared it with objective clinical data. MATERIALS AND METHODS: A total of 267 consecutive patients who underwent surgery for urethral stricture between March 1993 and December 1999 were questioned regarding satisfaction. Mailed questionnaires or a telephone interview, if questionnaires were not returned, provided information on the urinary tract, voiding, sexual function, overall satisfaction and miscellaneous impairments after surgery for urethral strictures. The response rate was 87% (233 of 267 patients). Subjective data were compared with objective clinical findings. RESULTS: Of the 203 patients who underwent successful urethroplasty 159 (78%) and 24 of the 30 (80%) in whom urethroplasty was considered a failure from the physician viewpoint were satisfied or very satisfied with the outcome of urethral surgery. Patients who underwent re-intervention for complications other than re-stricture and those who complained of a weak or very weak urinary stream were considerably less satisfied. Factors influencing sexual function also had an important impact on patient satisfaction. Patients with marked or severe penile curvature, penile shortening, erection deterioration and a markedly or severely impaired sexual life were especially dissatisfied. CONCLUSIONS: Patients consider the outcome of surgery for urethral strictures differently than physicians. The outcome of urethroplasty should be assessed not only by objective, but also by subjective criteria. Patients need appropriate preoperative counseling. With realistic expectations most men are satisfied with surgery for urethral stricture.     

A new therapeutic approach in medullary thyroid cancer treatment: inhibition of oncogenic RET signaling by adenoviral vector-mediated expression of a dominant-negative RET mutant

BACKGROUND: Mutations in the RET proto-oncogene that result in constitutive tyrosine kinase activity are the underlying cause for the development of medullary thyroid cancer (MTC). To investigate an alternative strategy in MTC treatment, we took advantage of a dominant-negative RET (dn-RET) mutant, Ret(51)HSCR32, which inhibits oncogenic signal transduction by retaining the oncogenic RET protein in the endoplasmic reticulum, thereby reducing the amount of oncogenic RET protein from the cell surface. METHODS; We constructed an adenoviral (Ad) vector expressing dn-RET under control of the C-cell specific synthetic calcitonin promoter TSE2.CP1 (AdTSE2.CP1-RET(51)HSCR32) and investigated the effect of dn-RET on cell growth of MTC-derived TT cells. RESULTS: Analysis of the subcellular localization of endogenous oncogenic RET protein showed a significant dominant-negative effect of Ad vector-delivered dn-RET in TT cells, resulting in a strong inhibition of cell viability. The observed effect is partially dependent on growth inhibition and possibly apoptosis induction. CONCLUSIONS: In the present study, growth of human MTC cells was successfully inhibited by Ad vector-mediated delivery of RET(51)HSCR32, suggesting that inhibition of oncogenic RET receptor tyrosine kinase expression by a dn-RET mutant might be a powerful approach for in vivo therapy of MTC.     

Ki67, E-cadherin, and p53 as prognostic indicators of long-term outcome after liver transplantation for metastatic neuroendocrine tumors

BACKGROUND: Patients suffering from hepatic metastases of neuroendocrine tumors (NET) are potential candidates for orthotopic liver transplantation. Because recurrence rates are high and outcome is variable, prognostic indicators are required. The aim of our study was to identify predictors of long-term survival with a focus on the impact of tumor biology. METHODS: We retrospectively analyzed 19 patients who received an orthotopic liver graft for metastatic NET at the Medizinische Hochschule Hannover. Expression of Ki67, E-cadherin, and p53 was studied immunohistochemically in metastases of neuroendocrine tumors of the explanted livers. RESULTS: Patients were followed up to 146 months after liver transplantation. Six patients died during follow-up. The resulting 1-, 5-, and 10-year survival rates are 89%, 80%, and 50%, respectively. All deaths during long-term follow-up were tumor-associated. Recurrence was diagnosed in 12 patients between 2 weeks and 48 months after liver transplantation. Three patients are without tumor recurrence more than 8 years after liver transplantation. Survival in the 5 patients with low Ki67 and regular E-cadherin staining was significantly better than in the 12 patients with high Ki67 or aberrant E-cadherin expression (7-year survival 100% vs. 0%, respectively, log rank P=0.007). p53 expression did not significantly improve prognostic accuracy. CONCLUSIONS: We conclude that analysis of Ki67 and E-cadherin expression may improve the identification of patients with a favorable prognosis after liver transplantation for metastatic neuroendocrine tumors.