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B Kramer

Publications and source records attributed to B Kramer.

At least 37 records · Page 2Linked to original sources
PubMed2000

The effect of retinoic acid on the proportion of insulin cells in the developing chick pancreas.

We assessed the potential role of all-trans-retinoic acid on the developing chick pancreas, specifically with regard to the proportions of insulin cells. The endodermal component of the dorsal pancreatic bud of 5-d-old chick embryos was cultured on Matrigel. Retinoic acid (10(-6) or 10(-5) M) was added to a standard serum-free medium, Ham's F12 containing insulin, transferrin and selenium (F12.ITS). Control grafts were cultured in F12.ITS alone or in F12.ITS with DMSO (the diluent for retinoic acid). After 7 d the explants were retrieved, freeze-dried, vapor-fixed, and embedded in resin. Endocrine cell types were identified by immunocytochemistry. The numbers of insulin cells were expressed as a proportion of the sum of insulin plus glucagon cells. Retinoic acid had a dose-related effect; the proportion of insulin cells in explants treated with the lower dose of retinoic acid (10(-6) M) was more than twice the proportion of insulin cells in explants treated with the higher dose (10(-5) M) of retinoic acid and more than three times that of the control grafts.

Animals↗
PubMed2000

Spatial and temporal localisation of bone morphogenetic protein-3 (osteogenin) in the developing rat submandibular gland.

Submandibular gland morphogenesis is a highly regulated process modulated by epithelio-mesenchymal interactions. Bone morphogenetic proteins (BMPs), members of the transforming growth factor-beta (TGF-beta) superfamily, are known to be soluble mediators of epithelio-mesenchymal interactions during the development of certain organs. The aim of this study was to localise bone morphogenetic protein-3 (BMP-3 or osteogenin), spatially and temporally in the developing rat submandibular gland. Immunocytochemistry was performed on sections of the developing submandibular gland (gestation ages E14.5-E19.5). BMP-3 was localised in the extra-cellular matrix of the mesenchyme of the gland in all the stages examined. Intense staining of BMP-3 was observed in the epithelial cells of the developing end-buds between stages E14.5 and E16.5. As cytodifferentiation progressed (stage E17.5 onwards) the number of epithelial cells in the developing acini in which BMP-3 was present became markedly reduced. Similarly, the number of cells containing BMP-3 in the developing ducts decreased as duct development progressed. By stage E19.5, BMP-3 was located mainly in the immature ducts. While the effects of BMP-3 on matrix macromolecules could not be deduced from this study, its spatial and temporal location within the developing glands may indicate a role in the co-ordinated regulation of branching morphogenesis.

Animals↗
PubMed1999

Evaluation of the FLEXX incremental construction algorithm for protein-ligand docking.

We report on a test of FLEXX, a fully automatic docking tool for flexible ligands, on a highly diverse data set of 200 protein-ligand complexes from the Protein Data Bank. In total 46.5% of the complexes of the data set can be reproduced by a FLEXX docking solution at rank 1 with an rms deviation (RMSD) from the observed structure of less than 2 A. This rate rises to 70% if one looks at the entire generated solution set. FLEXX produces reliable results for ligands with up to 15 components which can be docked in 80% of the cases with acceptable accuracy. Ligands with more than 15 components tend to generate wrong solutions more often. The average runtime of FLEXX on this test set is 93 seconds per complex on a SUN Ultra-30 workstation. In addition, we report on "cross-docking" experiments, in which several receptor structures of complexes with identical proteins have been used for docking all cocrystallized ligands of these complexes. In most cases, these experiments show that FLEXX can acceptably dock a ligand into a foreign receptor structure. Finally we report on screening runs of ligands out of a library with 556 entries against ten different proteins. In eight cases FLEXX is able to find the original inhibitor within the top 7% of the total library.

Algorithms↗
PubMed1999

Two-stage method for protein-ligand docking.

A two-stage method for the computational prediction of the structure of protein-ligand complexes is proposed. Given an experimentally determined structure of the protein, in the first stage a large number of plausible ligand conformations is generated using the fast docking algorithm FlexX. In the second stage these conformations are minimized and reranked using a method based on a classical force field. The two-stage method is tested for 10 different protein-ligand complexes. For 9 of them experimentally determined structures are known. It turns out that the two-stage method strongly improves the predictive power as compared to that of the fast docking stage alone. The tenth case is a bona fide prediction of a complex of thrombin with a new inhibitor for which no experimentally determined structure is available so far.

Algorithms↗
PubMed1999

Heterozygous germline mutations in the p53 homolog p63 are the cause of EEC syndrome.

EEC syndrome is an autosomal dominant disorder characterized by ectrodactyly, ectodermal dysplasia, and facial clefts. We have mapped the genetic defect in several EEC syndrome families to a region of chromosome 3q27 previously implicated in the EEC-like disorder, limb mammary syndrome (LMS). Analysis of the p63 gene, a homolog of p53 located in the critical LMS/EEC interval, revealed heterozygous mutations in nine unrelated EEC families. Eight mutations result in amino acid substitutions that are predicted to abolish the DNA binding capacity of p63. The ninth is a frameshift mutation that affects the p63alpha, but not p63beta and p63gamma isotypes. Transactivation studies with these mutant p63 isotypes provide a molecular explanation for the dominant character of p63 mutations in EEC syndrome.

Abnormalities, Multiple↗
PubMed1999

A non-invasive immobilization system and related quality assurance for dynamic intensity modulated radiation therapy of intracranial and head and neck disease.

PURPOSE: To develop and implement a non-invasive immobilization system guided by a dedicated quality assurance (QA) program for dynamic intensity-modulated radiotherapy (IMRT) of intracranial and head and neck disease, with IMRT delivered using the NOMOS Corporation's Peacock System and MIMiC collimator. METHODS AND MATERIALS: Thermoplastic face masks are combined with cradle-shaped polyurethane foaming agents and a dedicated quality assurance program to create a customized headholder system (CHS). Plastic shrinkage was studied to understand its effect on immobilization. Fiducial points for computerized tomography (CT) are obtained by placing multiple dabs of barium paste on mask surfaces at intersections of laser projections used for patient positioning. Fiducial lines are drawn on the cradle along laser projections aligned with nasal surfaces. Lateral CT topograms are annotated with a crosshair indicating the origin of the treatment planning and delivery coordinate system, and with lines delineating the projections of superior-inferior field borders of the linear accelerator's secondary collimators, or with those of the fully open MIMiC. Port films exposed with and without the MIMIC are compared to annotated topograms to measure positional variance (PV) in superior-inferior (SI), right-left (RL), and anterior posterior (AP) directions. MIMiC vane patterns superposed on port films are applied to verify planned patterns. A 12-patient study of PV was performed by analyzing positions of 10 anatomic points on repeat CT topograms, plotting histograms of PV, and determining average PV. RESULTS AND DISCUSSION: A 1.5+/-0.3 mm SD shrinkage per 70 cm of thermoplastic was observed over 24 h. Average PV of 1.0+/-0.8, 1.2+/-1.1, and 1.3+/-0.8 mm were measured in SI, AP, and RL directions, respectively. Lateral port films exposed with and without the MIMiC showed PV of 0.2+/-1.3 and 0.8+/-2.2 mm in AP and SI directions. Vane patterns superimposed on port films consistently verified the planned patterns. CONCLUSION: The CHS provided adequately reproducible immobilization for dynamic IMRT, and may be applicable to decrease PV for other cranial and head and neck external beam radiation therapy.

Brain Neoplasms↗
PubMed1999

The particle concept: placing discrete water molecules during protein-ligand docking predictions.

Water is known to play a significant role in the formation of protein-ligand complexes. In this paper, we focus on the influence of water molecules on the structure of protein-ligand complexes. We present an algorithmic approach, called the particle concept, for integrating the placement of single water molecules in the docking algorithm of FLEXX. FLEXX is an incremental construction approach to ligand docking consisting of three phases: the selection of base fragments, the placement of the base fragments, and the incremental reconstruction of the ligand inside the active site of a protein. The goal of the extension is to find water molecules at favorable places in the protein-ligand interface which may guide the placement of the ligand. In a preprocessing phase, favorable positions of water molecules inside the active site are calculated and stored in a list of possible water positions. During the incremental construction phase, water molecules are placed at the precomputed positions if they can form additional hydrogen bonds to the ligand. Steric constraints resulting from the water molecules as well as the geometry of the hydrogen bonds are used to optimize the ligand orientation in the active site during the reconstruction process. We have tested the particle concept on a series of 200 protein-ligand complexes. Although the average improvement of the prediction results is minor, we were able to predict water molecules between the protein and the ligand correctly in several cases. For instance in the case of HIV-1 protease, where a single water molecule between the protein and the ligand is known to be of importance in complex formation, significant improvements can be achieved.

Algorithms↗
PubMed1999

Authors' reply

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Journal Article↗
PubMed1999

Effect of exogenous gonadotropins on gonadotrophs of the rat pituitary gland.

In the human in vitro fertilization (IVF) program a variety of superovulation regimens have been employed to promote follicular stimulation and the recruitment of supernumerary oocytes. This therapy, however, disturbs serum concentrations of estradiol and progesterone and may disrupt the normal feedback systems of the hypothalamo-pituitary axis. This study examines the effects of hyperstimulation on the pituitary gonadotrophs and circulating gonadotrophins. FSH and human chorionic gonadotropin (hCG) were administered to normal cycling female Sprague-Dawley rats (n = 12) in phase with their estrous cycle. Control rats (n = 12) were injected with saline. In both the experimental and control groups, six rats were mated on the evening of proestrus and killed 12 hr later, while six animals were killed prior to mating. Blood was collected at the time of sacrifice for radioimmunoassay. The pituitary glands were removed, processed for light microscopy and serially sectioned. Immunocytochemistry for LH and FSH was carried out to determine the area occupied by these cell types. Data were statistically analyzed. Findings were correlated with circulating levels of LH, FSH, estradiol and progesterone. RIA revealed that the concentration of LH, FSH, estradiol and progesterone were significantly different with respect to hyperstimulation and mating. In addition the area occupied by LH and FSH cells was significantly different with respect to both hyperstimulation and mating. Hyperstimulation affects gonadotroph content, as well as gonadotropin and sex steroid hormone concentrations and together with other factors, may disrupt the ideal environment required for implantation.

Animals↗
PubMed1999

Ultrasound findings in children with toxocariasis: report on 18 cases.

PURPOSE: To evaluate abdominal ultrasound (US) findings in children infected with Toxocara canis. MATERIALS AND METHODS: Eighteen children, 18 months to 7 years of age, with serological diagnosis of T.canis infection underwent abdominal US. Eosinophil counts, hemoglobin levels and immunoglobulin E titers were measured for all patients. RESULTS: Abdominal ultrasound revealed multiple hypoechoic areas in the livers of 15 patients (83.3%). Hepatohilar lymph-node enlargement was present in 14 patients (77.7%), 2 of whom also showed peripancreatic lymph-node enlargement. Hepatomegaly was present in 13 patients (72.7%) and splenomegaly in 9 (50%). CONCLUSION: The most prevalent findings of abdominal ultrasound examination of children with T.canis infection are hepatic granulomas and abdominal lymph-node enlargement. This infection should be considered in the differential diagnosis of any children who exhibit these findings on abdominal US examination, especially for those with eosinophilia.

Animals↗
PubMed1999

Docking of hydrophobic ligands with interaction-based matching algorithms.

MOTIVATION: Matching of chemical interacting groups is a common concept for docking and fragment placement algorithms in computer-aided drug design. These algorithms have been proven to be reliable and fast if at least a certain number of hydrogen bonds or salt bridges occur. However, the algorithms typically run into problems if hydrophobic fragments or ligands should be placed. In order to dock hydrophobic fragments without significant loss of computational efficiency, we have extended the interaction model and placement algorithms in our docking tool FlexX. The concept of multi-level interactions is introduced into the algorithms for automatic selection and placement of base fragments. RESULTS: With the multi-level interaction model and the corresponding algorithmic extensions, we were able to improve the overall performance of FlexX significantly. We tested the approach with a set of 200 protein-ligand complexes taken from the Brookhaven Protein Data Bank (PDB). The number of test cases which can be docked within 1.5 A RMSD from the crystal structure can be increased from 58 to 64%. The performance gain is paid for by an increase in computation time from 73 to 91 s on average per protein-ligand complex. AVAILABILITY: The FlexX molecular docking software is available for UNIX platforms IRIX, Solaris and Linux. See http://cartan.gmd.de/FlexX for additional information.

Algorithms↗
PubMed1999

Waveform discrimination, phase sensitivity and jamming avoidance in a wave-type electric fish

The electric organ discharge (EOD) of most species of the freshwater knifefishes (Gymnotiformes) of South America is of the wave, not the pulse, type. Wave EODs are usually of constant frequency and amplitude, and show a bewildering multitude of species-characteristic waveforms. The EOD of Eigenmannia is sexually dimorphic in waveform and in the intensity of its higher harmonics. In a go/no go paradigm, trained food-rewarded fish discriminated between these waveforms, and naive (untrained) fish showed a significant preference. To determine whether spectral or waveform (time) cues are used by the fish, artificial stimuli of identical amplitude spectrum were synthesized that differed only in phase relationship between their harmonics, i.e. waveform, and the fish discriminated even among these stimulus waveforms (i.e. spectral cues are not required). Our sensory model predicts that, for successful waveform detection, a minimum frequency difference is required between the stimulus and the EOD. As expected, trained fish confused test stimuli of different waveform that were frequency-clamped and phase-locked to the EOD (frequency difference 0 Hz). Opening the electronic feedback loop immediately restored discrimination performance on an on/off basis, and a strong jamming avoidance response (JAR; a frequency shift away from the stimulus) accompanied every behavioural decision (to go for a food reward). The strong habituation of the JAR that occurs in response to stimuli of no behavioural consequence (the usual test situation) was not seen in the present experiments. The proposed sensory model (which is based on time-marking T electroreceptors) is supported by these experiments, and a biological function for the JAR - subserving EOD waveform discrimination is shown to be useful in a social context.

Journal Article↗
PubMed1999

The effect of temperature on sex determination using DNA-PCR analysis of dental pulp.

Forensic applications often necessitate the identification of human remains. This is made more difficult when the tissues have been exposed to high temperatures. Previously, metrical and non-metrical assessments of skeletal remains have been used to assess gender. Recent advances in molecular biology allow amplification of DNA from human blood, dental pulp and other tissues using the polymerase chain reaction (PCR), thus facilitating gender identification. The aim of this study was to investigate the efficacy of utilising DNA retrieved from the pulp of human teeth that had been exposed to different temperatures for different lengths of time, in order to assess gender. DNA was obtained from 94 teeth, 88 of which were isolated (44 male and 44 female), and six male teeth embedded in bone and soft tissue. A 106 base pair fragment from the X chromosome and a 112 base pair fragment from the Y chromosome was amplified from the amelogenin gene. PCR was shown to be 100% reliable when used to assess the gender of teeth which had been heated at 100 degrees C for 15 minutes but less reliable when the teeth were heated at higher temperatures for longer periods of time. Teeth encased in bone and soft tissue yielded better results when subjected to higher temperatures than did the isolated teeth.

Amelogenin↗
PubMed1998

Dosimetric verification of the dynamic intensity-modulated radiation therapy of 92 patients.

PURPOSE: To verify that optimized dose distributions provided by an intensity-modulated radiation therapy (IMRT) system are delivered accurately to human patients. METHODS AND MATERIALS: Anthropomorphic phantoms are used to measure IMRT doses. Four types of verification are developed for: I) system commissioning with beams optimized to irradiate simulated targets in phantoms, II) plans with patient-optimized beams directed to phantoms simulating the patient, III) patient-phantom hybrid plans with patient-optimized beams calculated in phantom without further optimization, and IV) in vivo measurements. Phantoms containing dosimeters are irradiated with patient-optimized beams. Films are scanned and data were analyzed with software. Percent difference between verified and planned maximum target doses is defined as "dose discrepancy" (deltavp). The frequency distribution of type II deltavp from 204 verification films of 92 IMRT patients is fit to a Gaussian. Measurements made in vivo yield discrepancies specified as deltaivp, also fit to a Gaussian. RESULTS AND DISCUSSION: Verification methods revealed three systematic errors in plans that were corrected prior to treatment. Values of [deltavp] for verification type I are <2%. Type II verification discrepancies are characterized by a Gaussian fit with a peak 0.2% from the centroid, and 158 [deltavp] <5%. The 46 values of [deltavp] >5% arise from differences between phantom and patient geometry, and from simulation, calculation, and other errors. Values of [deltavp] for verification III are less than half of the values of [deltavp] for verification II. A Gaussian fit of deltaivp from verification IV shows more discrepancy than the fit of deltavp, attributed to dose gradients in detectors, and exacerbated by immobilization uncertainty. CONCLUSIONS: Dosimetric verification is a critical step in the quality assurance (QA) of IMRT. Hybrid Verification III is suggested as a preliminary quality standard for IMRT.

Brain Neoplasms↗
PubMed1998

The origin of gut and pancreatic neuroendocrine (APUD) cells--the last word?

The evidence that gut and pancreatic endocrine cells are not derivatives of the neural crest is overwhelming: yet this conclusion is still not universally accepted. In this editorial attention is drawn to the body of experimental evidence which points conclusively to gut and pancreatic endocrine cells arising from endoderm, not the neural crest, the neurectoderm or neuroendocrine programmed epiblast.

APUD Cells↗
PubMed1998

Immunocytochemical identification of endocrine cells in the pancreas of the fruit bat, Rousettus aegyptiacus.

The fruit bat, Rousettus aegyptiacus, is able to absorb large amounts of glucose in very short periods of time. This ability is partly reflected by the structure of the gastrointestinal tract and pancreas. The aim of this study was to confirm preliminary histochemical studies of the bat pancreas and to identify and quantitate endocrine cells by immunocytochemical techniques in order to understand the ability of the bat to absorb these large amounts of glucose. Endocrine cells were distributed in islets throughout the gland and also occurred as discrete cells in the exocrine ducts. Three-dimensional reconstruction and quantitation showed that the endocrine component of the pancreas occupied 9.1% of the total volume. This is far more than that reported in any other species. Four endocrine cell types were demonstrated. Insulin (beta) cells (51.4%) were located throughout the islet and extended between the glucagon (alpha) cells (30.6%). Somatotostatin (delta) cells (8.8%) and pancreatic polypeptide (PP) cells (17.1%) were irregularly scattered throughout the islets. While the percentage of alpha, beta, and delta cells was similar to that in other species, the percentage of PP cells was higher. The high percentage of endocrine tissue found in the pancreas of the fruit bat may reflect metabolic adaptations involved in the absorption of the high carbohydrate diet of this animal.

Animals↗
PubMed1998

A quantitative assessment of the jugular foramen.

While it is generally accepted that the right jugular foramen is larger than the left, little quantitative evidence exists on the exocranial and endocranial openings of this foramen. The present study set out to clarify and quantify measurements of the two openings. The dimensions of the exocranial and endocranial openings of the jugular foramen and the volume and height of the jugular fossa were examined in a total sample of 93 skulls from white and black, male and female South Africans. The volume of the jugular fossa was determined with the use of a dental impression material. The exocranial area of the right jugular foramen was significantly larger (p < 0.05) than the left in the black group, while the endocranial area of the right foramen was significantly larger (p < 0.05) than the left only in black males. The height of the jugular fossa was significantly larger (p < 0.05) on the right side only in the black group. The volume of the jugular foramen was significantly larger (p < 0.05) on the right side only in females of both groups. Although the jugular foramen is generally larger on the right side than on the left, its size as well as the volume and height of the jugular fossa is variable in different groups and sexes.

Adult↗