[Course typologies of schizophrenic psychoses]. / Verlaufstypologien schizophrener Psychosen.

The "group of schizophrenias" describes a heterogeneous nosological construct with a variable course of the illness. Against this background, several historical approaches to course typologies of schizophrenic psychoses have been described (Bleuler; Huber; Leonhard; Watt, Katz and Shepherd). These concepts, however, differ considerably from each other, in particular with respect to the definition of outcomes. This mainly results from the reference to different psychopathological traditions. The possible codings of subgroups and course types of schizophrenic psychoses in ICD-10 and DSM-5 are compromises in order to combine the different aspects. The empirical examination and the advancement of course typologies of schizophrenic disorders using modern instruments and analyses are important tasks for current psychiatric research. Such efforts should combine quantitative-statistical analyses with a casuistic approach.

Slippery surfaces of pitcher plants: Nepenthes wax crystals minimize insect attachment via microscopic surface roughness.

Pitcher plants of the genus Nepenthes efficiently trap and retain insect prey in highly specialized leaves. Besides a slippery peristome which inhibits adhesion of insects they employ epicuticular wax crystals on the inner walls of the conductive zone of the pitchers to hamper insect attachment by adhesive devices. It has been proposed that the detachment of individual crystals and the resulting contamination of adhesive organs is responsible for capturing insects. However, our results provide evidence in favour of a different mechanism, mainly based on the stability and the roughness of the waxy surface. First, we were unable to detect a large quantity of crystal fragments on the pads of insects detached from mature pitcher surfaces of Nepenthes alata. Second, investigation of the pitcher surface by focused ion beam treatment showed that the wax crystals form a compact 3D structure. Third, atomic force microscopy of the platelet-shaped crystals revealed that the crystals are mechanically stable, rendering crystal detachment by insect pads unlikely. Fourth, the surface profile parameters of the wax layer showed striking similarities to those of polishing paper with low grain size. By measuring friction forces of insects on this artificial surface we demonstrate that microscopic roughness alone is sufficient to minimize insect attachment. A theoretical model shows that surface roughness within a certain length scale will prevent adhesion by being too rough for adhesive pads but not rough enough for claws.

Radioiodine therapy of colon cancer following tissue-specific sodium iodide symporter gene transfer.

We investigated the feasibility of using radioiodine therapy in colon carcinoma cells (HCT 116) following tumor-specific expression of the human sodium iodide symporter (hNIS) using the carcinoembryonic antigen (CEA) promoter. HCT 116 cells were stably transfected with an expression vector, in which hNIS cDNA has been coupled to a CEA promoter fragment. This promoter is responsible for tissue-specific expression of CEA in gastrointestinal tract epithelium, and has been shown to target therapeutic genes to colorectal cancer cells. Functional NIS expression was confirmed by iodide uptake assay, Western blot analysis, immunostaining and in vitro clonogenic assay. The stably transfected HCT 116 cells concentrated (125)I about 10-fold in vitro without evidence of iodide organification. In contrast, transfection of control cancer cells without CEA expression did not result in iodide accumulation. Western blot analysis using a hNIS-specific antibody revealed a band of approximately 90 kDa. In addition, immunostaining of stably transfected HCT 116 cells revealed hNIS-specific membrane-associated immunoreactivity. In an in vitro clonogenic assay approximately 95% of stably transfected HCT 116 cells were killed by exposure to (131)I, while only about 5% of NIS-negative control cells were killed. Further, using an adenovirus carrying the NIS gene linked to the CEA promoter, high levels of tumor-specific radioiodide accumulation were induced in HCT 116 cells. In conclusion, a therapeutic effect of (131)I has been demonstrated in colon carcinoma cells following induction of tumor-specific iodide uptake activity by CEA promoter-directed NIS expression in vitro. This study demonstrates the potential of NIS as a therapeutic gene allowing radioiodine therapy of colon cancer following tumor-specific NIS gene transfer.

Dexamethasone enhances the cytotoxic effect of radioiodine therapy in prostate cancer cells expressing the sodium iodide symporter.

Recently, we have reported the induction of prostate-specific radioiodine accumulation in prostate cancer cells (LNCaP) using a prostate-specific antigen (PSA)-promoter-directed expression of the sodium iodide symporter (NIS) gene. This offers the potential to treat prostate cancer with radioiodine. The aim of our current study was to examine the regulation of PSA-promoter-directed NIS expression in NIS-transfected LNCaP cells (NP-1) by dexamethasone (Dex). For this purpose, NIS mRNA and protein expression levels were examined in NP-1 cells by Northern and Western blot analysis, respectively, after incubation with Dex (10(-8)-10(-6) M) in the presence of 10(-9) M mibolerone. NIS functional activity was measured by iodide uptake assay. In addition, we examined regulation of in vitro cytotoxicity of 131-I by Dex in an in vitro clonogenic assay. After incubation with Dex, iodide accumulation in NP-1 cells increased up to 1.5-fold, whereas NIS mRNA and protein expression levels were increased up to 1.7-fold. This effect of Dex was blocked by the androgen receptor antagonist casodex (10(-6) M). The killing effect of 131-I in NP-1 cells was increased from 55% when incubated with mibolerone alone to 95% when treated with Dex (10(-7) M) plus mibolerone. Treatment of NP-1 cells with Dex resulted in an additional antiproliferative effect as measured by clonogenic assay and nonradioactive proliferation assay. In conclusion, in addition to an antiproliferative effect, treatment with Dex increases androgen-dependent NIS mRNA and protein expression as well as iodide accumulation, resulting in an increased cytotoxic effect of 131-I in prostate cancer cells stably expressing NIS under the control of the PSA-promoter.

[How to treat benign thyroid gland nodules]. / Hohe Dunkelziffer bei Schilddrüsenerkrankungen. Diagnostische Weichenstellung mit TSH und Sonographie.

Investigations within the framework of the thyroid gland initiative "Papillon" turned up an unexpectedly high level of pathogenic findings. Determination of TSH and sonography are considered the pillars of the diagnostic evaluation of the thyroid gland. Useful further investigations aimed at excluding functional disorders are, for example, the determination of FT3 and FT4 or a search for autoantibodies. To investigate suspicious nodules and to exclude malignant processes, additional scintigraphy and, were indicated, fine-needle puncture can be applied. Depending on the individual situation of the patient, the therapeutic option of choice is surgical operation or treatment with iodine-31 therapy. Medical treatment of nodular goiter is currently still controversial.

Retinoic acid-induced stimulation of sodium iodide symporter expression and cytotoxicity of radioiodine in prostate cancer cells.

We reported recently the induction of androgen-dependent iodide uptake activity in the human prostatic adenocarcinoma cell line LNCaP using a prostate-specific antigen (PSA) promoter-directed expression of the sodium iodide symporter (NIS) gene. This offers the potential to treat prostate cancer with radioiodine. In the current study, we examined the regulation of PSA promoter-directed NIS expression and therapeutic effectiveness of (131)I in LNCaP cells by all-trans-retinoic acid (atRA). For this purpose, NIS mRNA and protein expression levels in the NIS-transfected LNCaP cell line NP-1 were examined by Northern and Western blot analysis following incubation with atRA (10 (-9) to 10(-6) M) in the presence of 10(-9) M mibolerone (mib). In addition, NIS functional activity was measured by iodide uptake assay, and in vitro cytotoxicity of (131)I was examined by in vitro clonogenic assay. Following incubation with atRA, NIS mRNA levels in NP-1 cells were stimulated 3-fold in a concentration-dependent manner, whereas NIS protein levels increased 2.3-fold and iodide accumulation was stimulated 1.45-fold. This stimulatory effect of atRA, which has been shown to be retinoic acid receptor mediated, was completely blocked by the pure androgen receptor antagonist casodex (10(-6) M), indicating that it is androgen receptor dependent. The selective killing effect of (131)I in NP-1 cells was 50% in NP-1 cells incubated with 10(-9) M mib. This was increased to 90% in NP-1 cells treated with atRA (10(-7) M) plus 10(-9) M mib. In conclusion, treatment with atRA increases NIS expression levels and selective killing effect of (131)I in prostate cancer cells stably expressing NIS under the control of the PSA promoter. Therefore atRA may be used to enhance the therapeutic response to radioiodine in prostate cancer cells following PSA promoter-directed NIS gene delivery.

Comparative genomic hybridization in childhood acute lymphoblastic leukemia: correlation with interphase cytogenetics and loss of heterozygosity analysis.

We used comparative genomic hybridization (CGH) to study DNA copy number changes in 71 children with acute lymphoblastic leukemia (ALL) including 50 B-lineage and 21 T-ALLs. Forty-two patients (59%) showed genomic imbalances whereby gains were more frequently observed than losses (127 vs. 29). Gains most commonly affected the entire chromosomes 21 and 10 (19.7% each), 6, 14, 18, X (15.5% each), 17 (14.1%) and 4 (11.3%). Highly hyperdiploid karyotypes (chromosome number >50) occurred more frequently in B-lineage than in T-lineage ALL (24% vs. 4.8%). In both cell lineages deletions were mainly detected on 9p (14.1%) and 12p (8.4%), and on 6q in T-lineage ALL (4.2%). These findings were compared with loss of heterozygosity (LOH) of 6q, 9p, 11q, and 12p previously performed in 56 of the 71 patients. Among 54 sites of LOH, CGH revealed losses of the respective chromosome arms in 17 LOH-positive regions (31.5%). G-banding analysis and interphase cytogenetics with subregional probes for 14 loci confirmed the presence of genomic imbalances as detected by CGH. We, therefore, conclude that, in the absence of cytogenetic data, CGH represents a suitable method for identifying hyperdiploid karyotypes as well as prognostically relevant deletions in ALL patients.

Development of a monoclonal antibody for ELISA of CYP1A in primary cultures of rainbow trout Oncorhynchus mykiss hepatocytes.

Induction of cytochrome P4501A CYP1A in cultured cells can be used to determine the induction potencies of xenobiotics or complex environmental samples. This report describes the development of an enzyme linked immunosorbent assay ELISA for measurement of CYP1A expression in primary cultures of rainbow trout Oncorhynchus mykiss hepatocytes. Juvenile rainbow trout were injected with naphthoflavone BNF 25 mg kg-1 body weight to induce the synthesis of CYP1A. The CYP1A isoenzyme was purified, characterized by immunological cross reactivity and N terminal sequencing and used to prepare a monoclonal antibody in Balb C mice. The specificity of the antibody for CYP1A was proved by Western blotting of samples from control and BNF injected fish. Two ELISA methods, a direct and a competitive one, were evaluated, with both methods being of comparable sensitivity. Rainbow trout hepatocytes, maintained as monolayers in serum free, chemically defined medium, were exposed to naphthoflavone, and the induction response was measured both by 7 ethoxyresorufin O deethylase EROD activity and the direct ELISA method. Comparison between EROD activity and immunodetectable CYP1A protein can provide information on the catalytic efficiency of CYP1A.

Characterization of a cloned ribosomal fragment from mouse which contains the 18S coding region and adjacent spacer sequences.

The large EcoRI fragment of mouse ribosomal genes containing parts of the non-transcribed spacer, the external transcribed spacer located at the 5' end of the precursor molecule and about two thirds of the 18S sequence has been cloned in bacteriophage lambda gtWES. A physical map of the DNA was constructed by cleavage with several restriction endonucleases and hybridization of the restriction fragments of the recombinant DNA with labelled 18S and 45S rRNA. The orientation of the inserted fragment as well as the length of the 18S sequence was determined by electron microscopy of R-loop containing molecules. The absence of hybridization of the cloned fragment to other fragments in the genome shows that the non-transcribed spacer does not have a significant length of sequences in common with other sequences in the genome.

[On the etiology of spindle-shaped acid-fast bodies in the human spleen (author's transl)]. / Säurefeste Spindlekörper in der menschlichen Milz. Ein Beitrag zu ihrer Atiologie

Spindle-shaped acid-fast bodies have been identified only in lymph nodes till now. Their nature and their origin remained unclear. We have also found these bodies in the human spleen. Their staining reactions and their correlations to age, sex, weight of spleen, and to hemosiderin deposits were examined. They have been encountered in 50% of cases of hereditary spherocytosis and in 41.7% of cases of traumatic rupture of the spleen--but only in 2.3% of all other cases of groups of various other disorders. We conclude from our results that: 1. The spindle-shaped acid-fast bodies are made of ceroid. 2. They are not causative organisms and therefore cannot be of importance in the etiology of sarcoidosis. 3. They derive from increased destruction of erythrocytes. 4. They originate due to oxidative polymerization of membrane lipids. 5. They may also be found in absence of any fat-metabolism disturbance.