What limits tool use in nonhuman primates? Insights from tufted capuchin monkeys (Sapajus spp.) and chimpanzees (Pan troglodytes) aligning three-dimensional objects to a surface.

Perceptuomotor functions that support using hand tools can be examined in other manipulation tasks, such as alignment of objects to surfaces. We examined tufted capuchin monkeys' and chimpanzees' performance at aligning objects to surfaces while managing one or two spatial relations to do so. We presented six subjects of each species with a single stick to place into a groove, two sticks of equal length to place into two grooves, or two sticks joined as a T to place into a T-shaped groove. Tufted capuchins and chimpanzees performed equivalently on these tasks, aligning the straight stick to within 22.5° of parallel to the groove in approximately half of their attempts to place it, and taking more attempts to place the T stick than two straight sticks. The findings provide strong evidence that tufted capuchins and chimpanzees do not reliably align even one prominent axial feature of an object to a surface, and that managing two concurrent allocentric spatial relations in an alignment problem is significantly more challenging to them than managing two sequential relations. In contrast, humans from 2 years of age display very different perceptuomotor abilities in a similar task: they align sticks to a groove reliably on each attempt, and they readily manage two allocentric spatial relations concurrently. Limitations in aligning objects and in managing two or more relations at a time significantly constrain how nonhuman primates can use hand tools.

Observations on the effects of inhaled isoflurane in long-term sedation of critically Ill children using a modified AnaConDa©-system.

Long-term intravenous sedation may present problems due to dependence and side effects. Medical records of children who were administered isoflurane were reviewed. 15 patients (9 boys, 6 girls) with a mean age of 11.8 month (+2.4) were analysed.Analgesia and sedation was given in mean 9.7+1.1 days before commencing inhalation using a modified application device (AnaConDa©). Administration was given over a period of 7.2+1.4 days. Depth of sedation was monitored by using Comfort- and Hartwig-scores. Observations included continuous monitoring of heart-rate, pulse oxymetry, blood pressure and cerebral tissue oxygenation.Within 4 h post administration of isoflurane a satisfactory increase in the depth of sedation was seen and kept till extubation. 6/15 patients received tracheostomies during the observation period. None of the patients observed suffered life-critical events of the modified application of isoflurane proceeded without complications. Ketamine and clonidine infusion rates were significantly reduced (p<0.005) as well as the use and overall infusion rate of midazolam, γ-hydroxy butyrate, fentanyl and morphine (p<0.05).Isoflurane inhalation may provide an additional option for long-term sedation in a specific group of critically ill infants but neurodegenerative toxic effects will have to be taken into account when using volatile anesthetics at any time during infancy.

Understanding the electric and magnetic response of isolated metaatoms by means of a multipolar field decomposition.

We introduce a technique to decompose the scattered near field of two-dimensional arbitrary metaatoms into its multipole contributions. To this end we expand the scattered field upon plane wave illumination into cylindrical harmonics as known from Mie's theory. By relating these cylindrical harmonics to the field radiated by Cartesian multipoles, the contribution of the lowest order electric and magnetic multipoles can be identified. Revealing these multipoles is essential for the design of metamaterials because they largely determine the character of light propagation. In particular, having this information at hand it is straightforward to distinguish between effects that result either from the arrangement of the metaatoms or from their particular design.

Asymmetric transmission of linearly polarized light at optical metamaterials.

We experimentally demonstrate a three-dimensional chiral optical metamaterial that exhibits an asymmetric transmission for forwardly and backwardly propagating linearly polarized light. The observation of this novel effect requires a metamaterial composed of three-dimensional chiral meta-atoms without any rotational symmetry. Our analysis is supported by a systematic investigation of the transmission matrices for arbitrarily complex, generally lossy media that allows deriving a simple criterion for asymmetric transmission in an arbitrary polarization base. Contrary to physical intuition, in general the polarization eigenstates in such three-dimensional and low-symmetry metamaterials do not obey fixed relations and the associated transmission matrices cannot be symmetrized.

[Characterization and management of incidentally detected solitary pulmonary nodules]. / Charakterisierung und Management inzidentell diagnostizierter solitärer Lungenrundherde.

How to deal with solitary pulmonary nodules (SPN) which are incidentally detected by computed tomography (CT) is an increasingly important task in the era of modern multislice CT. This paper reviews the morphological and functional characteristics and their value for discrimination between benign and malignant SPNs. In particular, the importance of nodule size, growth rate, margin morphology, density, calcifications or fatty components within the nodules, the significance of cavitations or aerobronchograms, enhancement patterns at dynamic contrast-enhanced CT and findings on positron emission tomography (PET) are discussed. The Bayesian analysis to calculate the probability of malignancy is presented. Finally, flow charts demonstrate the national and international recommendations for nodule management.

Population dynamics of caterpillars on three cover crops before sowing cotton in Mato Grosso (Brazil).

Direct seeding mulch-based cropping systems under a preliminary cover crop such as millet are common in some areas of Brazil. Lepidopteran pests that damage cotton, soybean and maize crops can proliferate on cover crops, so preventive chemical treatments are necessary. Very little data is available on these pests on cover crops. This paper presents the dynamics of Spodoptera frugiperda, S. eridania, Mocis latipes and Diatraea saccharalis caterpillars monitored at Primavera do Leste, Mato Grosso state (Brazil) during the of 2005/2006 and 2006/2007 cropping seasons on four cover crops, i.e. finger millet (Eleusine coracana), pearl millet (Pennisetum glaucum), sorghum (Sorghum bicolor) and ruzigrass (Brachiaria ruziziensis). The pests were visually counted on plants within a 1 m2 transect (wooden frame). Caterpillars were reared to facilitate identification of collected species and parasitoids. Many S. frugiperda caterpillars were observed on millet in 2005, with a maximum of 37 caterpillars/m2. On sorghum, we found 30 caterpillars/m2, or 0.83 caterpillars/plant. The Diatraea borer attacked sorghum later than the other pests. M. latipes was also observed on millet. The millet cover crop had to be dried for at least 1 month before direct drilling the main cotton crop in order to impede S. frugiperda infestations on cotton plantlets, thus avoiding the need for substantial resowing. The comparative methodological aspects are discussed.

Hypergonadotropic hypogonadism in a patient with inv ins (2;4).

We report on a 30-year-old man with azoospermia, primary hypogonadism and minor dysmorphic features who carried a balanced insertional chromosome translocation inv ins (2p24;4q28.3q31.22)de novo. Molecular cytogenetic analyses of the chromosome breakpoints revealed the localization of the breakpoint in 4q28.3 between BACs RP11-143E9 and RP11-285A15, an interval that harbours the PCDH10 gene. In 4q31.22, a breakpoint-spanning clone (RP11-6L6) was identified which contains the genes LSM6 and SLC10A7. On chromosome 2, BACs RP11-531P14 and RP11-360O18 flank the breakpoint in 2p24, a region void of known genes. In conclusion, the chromosome aberration of this patient suggests a gene locus for primary hypogonadism in 2p24, 4q28.3 or 4q31.2, and three possible candidate genes (LSM6, SLC10A7 and PCDH10) were identified by breakpoint analyses.

Pre-surgical evaluation of ICA-stenosis using 3D power Doppler, 3D color coded Doppler sonography, 3D B-flow and contrast enhanced B-flow in correlation to CTA/MRA: first clinical results.

AIM: Pre-surgical evaluation of the extent of internal carotid artery stenosis (ICA) according to NASCT criteria using digital 3D ultrasound methods. MATERIAL/METHODS: In a prospective study, 25 patients (54-88 years, mean 75) with neurological deficits and the diagnosis of ICA stenosis underwent pre-surgical ultrasound examination using Color Coded Duplex Sonography (CCDS), 3D CCDS, 3D power Doppler, 3D B-flow, contrast enhanced 3D B-flow, and CTA/MRA. Ultrasound was performed by an experienced examiner with a multifrequency linear transducer (6-9 MHz, Logiq 9, GE). After bolus injection of 2.4 ml Sonovue i.v., low mechanical index technique (MI<0.16) was used for contrast enhanced 3D B-flow. As reference method for evaluation of the extent of ICA stenosis each patient underwent CTA (multislice CT, Sensation 16, Siemens) and/or MRA (1.5 T, Symphony Siemens). Indications for surgery (carotid EEA) followed the NASCET criteria. All images were interpreted and evaluated independently by two observers with three measurements of the degree of the ICA stenosis. For assessment of the extent of stenosis a 10%-scale from 50% to 99% was used. Statistical analysis was performed using Spearman Correlation and Wilcoxon Signed Rank Test with a significance threshold of p<0.05. RESULTS: Assessment of the extent of ICA stenosis during surgery and in CTA/MRA displayed a range from 60% to 99% (mean 80%). Non significant differences were found with paired Wilcoxon test only for 3D B-flow with and without contrast medium (p<0.05). Correlation with surgical evaluation regarding the extent of ICA stenosis using Spearman correlation teat was 0.77 for B-scan, 0.90 for 3D CCDS, 0.84 for 3D Power Doppler, 0.91 for B-flow and 0.93 for contrast enhanced 3D B-flow. When circular calcifications were present, contrast enhanced flow detection of 3D B-flow proved to be useful. Visualisation of intrastenotic variances of severe and profound stenosis (70-99%) without blooming and reverberation artefacts was possible only with 3D B-flow. This facilitates the detection of the morphology of plaques ulcers as an embolic source. CONCLUSION: In correlation with surgery and CTA/MRA, a valid evaluation of the extent and morphology of ICA stenosis using 3D B-flow, with and without contrast medium, is feasible.

[Tissue engineering of bone tissue. Principles and clinical applications]. / Tissue Engineering von Knochengewebe: Prinzipien und klinische Anwendungsmöglichkeiten.

Complex fractures are still a major clinical challenge. The treatment options of large bony defects either with autografts or allografts are limited in terms of material availability and tissue in-growth. Tissue engineering might offer a solution to this problem. In an interdisciplinary approach artificial bony tissue can be generated which mimics normal bone in terms of function and morphology. So far tissue engineering of bone is mainly confined to laboratory investigations whereas clinical applications are still in the beginning. This manuscript presents the most important scaffolds as well as growth factors and cell systems. Furthermore, it focuses on clinical studies for the treatment of large bony defects using tissue engineered cell-matrix constructs.

Breakpoints around the HOXD cluster result in various limb malformations.

BACKGROUND: Characterisation of disease associated balanced chromosome rearrangements is a promising starting point in the search for candidate genes and regulatory elements. METHODS: We have identified and investigated three patients with limb abnormalities and breakpoints involving chromosome 2q31. Patient 1 with severe brachydactyly and syndactyly, mental retardation, hypoplasia of the cerebellum, scoliosis, and ectopic anus, carries a balanced t(2;10)(q31.1;q26.3) translocation. Patient 2, with translocation t(2;10)(q31.1;q23.33), has aplasia of the ulna, shortening of the radius, finger anomalies, and scoliosis. Patient 3 carries a pericentric inversion of chromosome 2, inv(2)(p15q31). Her phenotype is characterised by bilateral aplasia of the fibula and the radius, bilateral hypoplasia of the ulna, unossified carpal bones, and hypoplasia and dislocation of both tibiae. RESULTS: By fluorescence in situ hybridisation, we have mapped the breakpoints to intervals of approximately 170 kb or less. None of the three 2q31 breakpoints, which all mapped close to the HOXD cluster, disrupted any known genes. CONCLUSIONS: Hoxd gene expression in the mouse is regulated by cis-acting DNA elements acting over distances of several hundred kilobases. Moreover, Hoxd genes play an established role in bone development. It is therefore very likely that the three rearrangements disturb normal HOXD gene regulation by position effects.

Multiparameter scoring system for the prognosis of differentiated thyroid cancer.

UNLABELLED: The AIM of the study was to develop a scoring system consisting of multiple parameters that are significant for prognosis of thyroid cancer. The score was designed to permit a risk stratification with all available information at any time of presentation. PATIENTS, METHODS: A score using 25 parameters was used for 171 patients with differentiated thyroid cancer, who were included in follow up over a mean of 9 (+/- 5) years. The significance of each parameter as well as of a summation outcome score was determined. The result of this scoring system was compared to other scores reported in the literature applied to the same patients' group. Thirty-two out of the 171 patients presented with recurrence during follow up. RESULTS: The summation score was highly significant for prognosis of differentiated thyroid cancer. Out of 25 parameters, 18 showed a significant association with outcome also as individual parameters. In comparison to the scores commonly used, this new system showed the highest significance (p < 0.0001, chi square 90, df 1) to estimate recurrence free survival. At a cutoff of -5.95 the sensitivity and specificity for the distinction between high and low risk patients were 87.5 and 77.0%, respectively. CONCLUSION: With our multiparameter scoring system a reliable prognosis with respect to recurrence free survival is possible in patients suffering from differentiated thyroid cancer. A summation score of all parameters gives the best results. Scoring is also possible, if several important parameters are missing.

Impact of low copy repeats on the generation of balanced and unbalanced chromosomal aberrations in mental retardation.

Low copy repeats (LCRs) are stretches of duplicated DNA that are more than 1 kb in size and share a sequence similarity that exceeds 90%. Non-allelic homologous recombination (NAHR) between highly similar LCRs has been implicated in numerous genomic disorders. This study aimed at defining the impact of LCRs on the generation of balanced and unbalanced chromosomal rearrangements in mentally retarded patients. A cohort of 22 patients, preselected for the presence of submicroscopic imbalances, was analysed using submegabase resolution tiling path array CGH and the results were compared with a set of 41 patients with balanced translocations and breakpoints that were mapped to the BAC level by FISH. Our data indicate an accumulation of LCRs at breakpoints of both balanced and unbalanced rearrangements. LCRs with high sequence similarity in both breakpoint regions, suggesting NAHR as the most likely cause of rearrangement, were observed in 6/22 patients with chromosomal imbalances, but not in any of the balanced translocation cases studied. In case of chromosomal imbalances, the likelihood of NAHR seems to be inversely related to the size of the aberration. Our data also suggest the presence of additional mechanisms coinciding with or dependent on the presence of LCRs that may induce an increased instability at these chromosomal sites.

FDG uptake after intraarterial chemotherapy in head and neck cancer.

AIM: The intraarterial chemotherapy (i.a.CHT) using high dose cisplatin combined with systemic neutralization in patients with head and neck cancer (HNSCC) is used to reduce the tumor volume preoperatively. Aim of the study is the evaluation of the influence of i.a.CHT on the metabolism of fluor-18-deoxyglucose (FDG) in the primary and lymph nodes (LN). The value of FDG positron emission tomography (PET) preoperative and as follow-up method after i.a.CHT is examined. PATIENTS, METHODS: Altogether 16 patients with HNSCC underwent two preoperative FDG PET examinations: the baseline examination one week before and the follow-up three weeks after i.a.CHT. The SUVmax values of the primary and the LN and LN metastases were evaluated and compared with each other and the histopathology. RESULTS: The SUVmax value of the primary decreased after i.a.CHT significantly from a median (25 (th) percentile/75 (th) percentile) of 6.4 (4.1/7.8) to 3.6 (2.4/6.7) (p = 0.01). In 11 out of 16 patients cervical LN metastases were detected. The cervical LN metastases showed a decrease of the SUVmax value from 3.6 (2.3/4.8) in the pretreatment examination to 2.3 (1.7/3.6) after i.a.CHT (p = 0.008). Only in one patient with LN metastases the SUVmax of the nodes increased. The histopathologically measured size of the LN metastases ranged from 2 to 30 mm. Non malignant LN did not reveal a significant SUVmax decrease after i.a.CHT (p = 0.13). CONCLUSIONS: As expected, primaries of HNSCC showed a significant reduction of SUV after i.a.CHT. Compared to the primary the SUVmax decrease in LN metastases was less, but also significant. Since cytotoxic levels of cisplatin do not occur systemic, postinflammatory reactions of the LN or a lymphatic drainage of the chemotherapeutic drug into the LN could be an explanation. PET for staging of HNSCC must thus be performed prior to i.a.CHT.

Therapy of hepatocellular carcinoma with iodine-131-lipiodol. Results in a large German cohort.

AIM: To evaluate the efficacy and tolerance of iodine-131-lipiodol ((131)I-lipiodol) for hepatocellular carcinoma (HCC) in German long term patients and comparison with medically treated controls. PATIENTS, METHODS: 38 courses of intra-arterial (131)I-lipiodol therapy with a total activity up to 6.7 GBq were performed in 18 patients with HCC (6 with portal vein thrombosis). Liver and tumour volume and lipiodol deposition were measured by computed tomography and (131)I activity by scintigraphy. Therapeutic efficacy was determined by tumour volume change and matched-pairs analysis in comparison to medically (i.e. tamoxifen or medical support) treated patients. RESULTS: Tumour volume decreased in 20/32 index nodules (63%) after the first course. Repeated therapy frequently resulted in further tumour reduction. Overall response to treatment was partial in 11 nodules, minor response in 4 nodules, and disease was stable in 12 and progressive in 5. Significant response was associated with pretherapeutic nodule volume up to 150 ml (diameter of 6.6 cm). Survival rate after 3, 6, 9, 12, 24 and 36 months was 78, 61, 50, 39, 17, and 6%. Matched-pairs analysis of survival revealed (131)I-lipiodol to be superior to medical treatment. The most important side effect was a pancreatitis-like syndrome whereas overall tolerance was good. CONCLUSION: The long term results confirm that HCC therapy with (131)I-lipiodol is effective and probably superior to medical treatment. Tumour nodules of up to 6 cm diameter are well suited for this therapy even in the presence of portal vein thrombosis.

Protein, lipid and water organization in bacteriorhodopsin crystals: a molecular view of the purple membrane at 1.9 A resolution.

BACKGROUND: Bacteriorhodopsin (bR) from Halobacterium salinarum is a proton pump that converts the energy of light into a proton gradient that drives ATP synthesis. The protein comprises seven transmembrane helices and in vivo is organized into purple patches, in which bR and lipids form a crystalline two-dimensional array. Upon absorption of a photon, retinal, which is covalently bound to Lys216 via a Schiff base, is isomerized to a 13-cis,15-anti configuration. This initiates a sequence of events - the photocycle - during which a proton is transferred from the Schiff base to Asp85, followed by proton release into the extracellular medium and reprotonation from the cytoplasmic side. RESULTS: The structure of bR in the ground state was solved to 1.9 A resolution from non-twinned crystals grown in a lipidic cubic phase. The structure reveals eight well-ordered water molecules in the extracellular half of the putative proton translocation pathway. The water molecules form a continuous hydrogen-bond network from the Schiff-base nitrogen (Lys216) to Glu194 and Glu204 and includes residues Asp85, Asp212 and Arg82. This network is involved both in proton translocation occurring during the photocycle, as well as in stabilizing the structure of the ground state. Nine lipid phytanyl moieties could be modeled into the electron-density maps. Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) analysis of single crystals demonstrated the presence of four different charged lipid species. CONCLUSIONS: The structure of protein, lipid and water molecules in the crystals represents the functional entity of bR in the purple membrane of the bacteria at atomic resolution. Proton translocation from the Schiff base to the extracellular medium is mediated by a hydrogen-bond network that involves charged residues and water molecules.

A cryptic deletion of 2q35 including part of the PAX3 gene detected by breakpoint mapping in a child with autism and a de novo 2;8 translocation.

We report a de novo, apparently balanced (2;8)(q35;q21.2) translocation in a boy with developmental delay and autism. Cross species (colour) paint (Rx) and SKY FISH, forward and reverse chromosome painting, and FISH with subtelomeric probes were used to examine the patient's karyotype, but further rearrangements were not detected. FISH with region specific clones mapping near 2q35 and 8q21.2 breakpoints and STS mapping performed on the isolated derivative chromosomes were used to refine the location of the breakpoints further. A cryptic deletion of between 4.23 and 4.41 Mb in extent and involving at least 13 complete genes or transcription units was found at the breakpoint on 2q35. The deletion includes the promoter and 5' untranslated region of the paired box 3 (PAX3) gene. The child has very mild dystopia canthorum which may be associated with the PAX3 haploinsufficiency. The 8q21.2 breakpoint is within MMP16 which encodes matrix metalloproteinase 16. We postulate that the cryptic deletion and rearrangement are responsible for the patient's phenotype and that a gene (or genes) responsible for autism lies at 2q35 or 8q21.2. The results present a step towards identifying genes predisposing to autism.

Increased FDG bone marrow uptake after intracoronary progenitor cell therapy.

UNLABELLED: Patients with coronary artery disease who undergo FDG, PET for therapy monitoring after intracoronary progenitor cell infusion (PCT) show an increased bone marrow uptake in some cases. AIM of the study was to evaluate the systemic bone marrow glucose metabolism in this patient group after PCT. PATIENTS, METHODS: FDG bone marrow uptake (BMU), measured as standardized uptake value (SUVmax) in the thoracic spine, was retrospectively evaluated in 23 control patients who did not receive PCT and in 75 patients who received PCT 3 +/- 2.2 days before PET scanning. Five out of them were pretreated with granulocyte colony-stimulating factor (G-CSF) 5 days prior to PCT and 10 +/- 1.2 days before PET scanning. In 39 patients who received only PCT without G-CSF and underwent PET therapy monitoring 4 months later, baseline and follow up bone marrow uptake were measured. Leucocytes, C-reactive protein (CRP) levels and the influence of nicotine consumption were compared with the BMU. RESULTS: In patients (n = 70) who received PCT without G-CSF, BMU median (1.3) was slightly, but significantly higher than in the controls (1.0) (p = 0.02) regardless nicotine consumption. BMU did not change significantly 4 months later (1.2) (p = 0.41, n.s.). After G-CSF pretreatment, patients showed a significantly higher bone marrow uptake (3.7) compared to patients only treated with PCT (1.3) (p = 0.023). Leucocyte blood levels were significantly higher in patients with a BMU > or =2.5 compared to patients with a bone marrow SUVmax <2.5 (p<0.001). CRP values did not correlate with the BMU (rho -0.02, p = 0.38). CONCLUSION: Monitoring PCT patients, a slightly increased FDG BMU may be observed which remains unchanged for several months. Unspecific bone marrow reactions after PCT may be associated with increased leucocyte blood levels and play a role in the changed systemic glucose BMU. In addition, pretreatment with G-CSF shows an intense amplification of BMU.

Residual kidney function after donor nephrectomy. Assessment by 99mTc-MAG3-clearance.

AIM: We evaluated the long-term residual renal function after donor nephrectomy using 99mTc-mercaptoacetyltriglycin (MAG3)-clearance. DONORS, METHODS: Altogether 49 kidney donors were examined using 99mTc-MAG3-clearance after nephrectomy for donation to a relative (m:f = 11:38; age 55+/-27 years). The donors were examined 16+/-8 years postoperatively (1.5-26 years). 42 donors (86%) showed normal creatinine values, whereas the other seven (14%) exhibited slightly elevated levels. 20 donors were examined pre- and postoperatively and compared intraindividually. The kidney function was compared to the age adapted normal values of healthy persons with two kidneys (67-133% of age related mean). RESULTS: After nephrectomy all donors showed a normal perfusion, good secretion, merely physiological intrarenal transit and a normal elimination from the kidneys. The 99mTc-MAG3-clearance was 69+/-15% of the normal mean value of healthy carriers of two kidneys regardless of the gender. 20 donors with a preoperative examination showed a significantly reduced total renal function from 84+/-15% of the mean normal value preoperatively to 60+/-15% postoperatively (p <0.0005). 15 donors of this group exhibited a significant functional increase of the residual kidney from 40% initially to 60% after nephrectomy (p = 0.003). No correlation was found between the initial-99mTc-MAG3-clearance measured prior to nephrectomy and the clearance levels after nephrectomy. Also, no correlation between the preoperative 99mTc-MAG3-clearance and the postoperative serum creatinine values could be observed. Altogether, 22% of the donors (11/49) developed arterial hypertension 10+/-8 years after donation (1-23 years). This corresponds to the normal age prevalence of hypertension in the carriers of two kidneys. Three donors suffered from arterial hypertension prior to the operation. CONCLUSION: Kidney donors with normal or slightly elevated creatinine values postoperatively show a 99mTc-MAG3-clearance value of 69% of the mean value of healthy carriers of two kidneys. This may serve as a reference value for healthy carriers of one kidney. In our study we demonstrated a good compensation of the contralateral kidney via renal scintigraphy by means of 99mTc-MAG3-clearance.

Protein phosphatase 2A, a potential regulator of actin dynamics and actin-based organelle motility in the green alga Acetabularia.

The giant, unicellular alga Acetabularia is a well known experimental model for the study of actin-dependent intracellular organelle motility. In the cyst stage, however, which is equivalent to the gametophytic stage, organelles are immobile, even though an actin cytoskeleton is present. The reason for the lack of organelle motility at this stage has not been known. To test the hypothesis that organelle motility could be under the control of posttranslational modification by protein phosphorylation, we have treated cysts with submicromolar concentrations of okadaic acid or calyculin A, both potent inhibitors of serine/threonine protein phosphatases (ser/thr-PPases). The effects were dramatic: Instead of linear actin bundles typical for control cysts, circular arrays of actin bundles formed in the cortical cyst cytoplasm. Concomitant with the formation of these action rings, the cytoplasmic layers beneath the rings began to slowly rotate in a continuous and uniform counter-clockwise fashion. This effect suggests that protein phosphorylation acts on the actin cytoskeleton at two levels: (1) It changes the assembly properties of the actin filament system to the extent that novel cytoskeletal configurations are formed and (2) it raises the activity of putative motor proteins involved in the rotational movements to levels sufficiently high to support motility at a stage when organelle motility does not normally occur. Northern blot analysis of cyst stage-mRNA using probes specific to protein phosphatase type 1 (PP1) and type 2A (PP2A) reveals that PP2A is strongly expressed at this developmental stage whereas PP1 is not detectable, suggesting that PP2A is the likely target to the protein phosphatase inhibitors.(ABSTRACT TRUNCATED AT 250 WORDS)

[123I]IBZM SPECT for imaging of striatal D2 dopamine receptors in 56 schizophrenic patients taking various neuroleptics.

OBJECTIVE: The purpose of this study was to compare the binding of various typical and atypical neuroleptics to striatal D2 dopamine receptors in schizophrenic patients. METHOD: Fifty-six inpatients with schizophrenia, including 14 with schizoaffective disorder and one with schizophreniform disorder, were evaluated. Fourteen patients were neuroleptic free. Single photon emission computed tomography (SPECT) was performed 90 minutes after intravenous injection of [123I]benzamide ([123I]IBZM). Subsequent semiquantitative analysis of D2 receptor binding was done with the use of the basal ganglia (striatum)/frontal cortex (BG/FC) ratio of activity. Clinical symptoms were rated with the Positive and Negative Syndrome Scale and the Hamilton Depression Rating Scale. RESULTS: The BG/FC ratios in patients taking typical neuroleptics were significantly lower than those in the neuroleptic-free subjects but not lower than those in the patients taking atypical neuroleptics (clozapine, remoxipride). For atypical antipsychotics, a dose-dependent relationship with striatal D2 receptor binding could not be demonstrated. BG/FC ratios were not significantly correlated with clinical symptoms or with duration of illness. CONCLUSIONS: The results indicate that [123I]IBZM SPECT is useful for semiquantitative imaging of striatal D2 dopamine receptors and for estimating their blockade by neuroleptics. Thus, it may improve drug monitoring in psychiatric patients. Furthermore, the findings suggest a complex relationship between the antipsychotic effect of atypical neuroleptics and D2 receptor blockade.