[Nobel prize in medicine for banana fly research].
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Biomedical subjects
Publications and source records attributed to C Roos.
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RATIONALE AND OBJECTIVES: A prior study indicated that differences in the x-ray linear attenuation coefficients of cancerous and normal breast tissues tend to increase as the energy of the incident beam decreases. The authors investigated x-ray energies down to 20 keV. In the current study, the linear attenuation coefficients for normal and selected cancerous breast tissues within the energy range of 14 to 18 keV were determined. METHODS: Fifty breast biopsy specimens consisting of a mixture of breast malignancies, normal tissues, fat specimens, and tumors grown in rats were used. X-ray linear attenuation coefficients were measured for each sample within the energy range of 14.15 to 18 keV, using monoenergetic x-rays from beamline X-19A at the National Synchrotron Light Source at Brookhaven National Laboratory. Each sample was measured at 130 different energies starting at 14.15 keV with step sizes of 0.030 keV. Correlation of the measured attenuation coefficients for cellular makeup was performed. RESULTS: The mean of linear attenuation coefficients for samples classified as "cancers" was 10.9% higher than the mean of samples classified as "normal" breast tissues and was 66.5% higher than the mean of samples classified as normal breast fat. CONCLUSIONS: Differences in the linear attenuation coefficients of monochromatic x-rays between 14.15 and 18 keV do exist between normal and cancerous tissues, but there is some degree of overlap.
The diazepam-binding inhibitor (DBI; also called acyl coenzyme A-binding protein or endozepine) is a 10-kDa polypeptide found in organisms ranging from yeasts to mammals. It has been shown that DBI and its processing products are involved in various specific biological processes such as GABAA/benzodiazepine receptor modulation, acyl coenzyme A metabolism, steroidogenesis, and insulin secretion. We have cloned and sequenced the Drosophila melanogaster gene and cDNA encoding DBI. The Drosophila DBI gene encodes a protein of 86 amino acids that shows 51 to 56% identity with previously known DBI proteins. The gene is composed of one noncoding 5' and two coding exons and is localized on the chromosomal map at position 65E. Several transcription initiation sites were detected by RNase protection and primer extension experiments. Computer analysis of the promoter region revealed features typical of housekeeping genes, such as the lack of TATA and CCAAT elements. However, in its low GC content and lack of a CpG island, the region resembles promoters of tissue-specific genes. Northern (RNA) analysis revealed that the expression of the DBI gene occurred from the larval stage onwards throughout the adult stage. In adult flies, DBI mRNA and immunoreactivity were detected in the cardia, part of the Malpighian tubules, the fat body, and gametes of both sexes. Developmentally regulated expression, disappearing during metamorphosis, was detected in the larval and pupal brains. No expression was detected in the adult nervous system. On the basis of the expression of DBI in some but not all tissues with high energy consumption, we propose that in D. melanogaster, DBI is involved in energy metabolism in a manner that depends on the substrate used for energy production.
BACKGROUND: Vasoactive drugs could alter the fluid restitution from the tissue and redistribute blood volume between the macrocirculation and microcirculation. METHODS AND RESULTS: With bolus injections of vasoactive drugs in anesthetized rabbits, we measured the changes in blood and plasma density for the determination of the volume of restitution and redistribution. Epinephrine 3.5 micrograms/kg caused a fluid loss to the tissue, leading to a transient decrease in total blood volume by 2.30 mL/kg. Because of blood volume redistribution, the peak volume reduction was accompanied by a volume reduction of 0.81 mL/kg from the macrocirculation and 1.49 mL/kg from the microcirculation. Phenylephrine 70 micrograms/kg caused a peak reduction in total blood volume of 1.40 mL/kg (with 0.41 mL/kg from macrocirculation and 0.99 mL/kg from microcirculation). Nitroprusside 7 micrograms/kg increased the blood volume by 1.44 mL/kg (0.83 mL/kg macro and 0.61 mL/kg micro), nitroglycerin 7 micrograms/kg by 1.48 mL/kg (0.97 mL/kg macro and 0.51 mL/kg micro), and isoproterenol 7 micrograms/kg by 2.07 mL/kg (0.68 mL/kg macro and 1.39 mL/kg micro). All plasma (or blood) density changes measured for the five drugs (with epinephrine, phenylephrine, and nitroprusside done over a wide dosage range) correlated linearly with the drug-induced changes in arterial pressures. CONCLUSIONS: These results indicate that vasoactive drugs alter total blood volume and the volume of microcirculation and macrocirculation.
We have studied the role of three loci, quit, ovarian tumor and shut down during oocyte differentiation in Drosophila by using in situ hybridisation and double mutant analyses. Mutations in qui and otu disturb the cystocyte divisions and the oocyte determination, while mutations in shu affect the cystocyte integrity, nevertheless allowing differentiation of normal-looking egg chambers with an oocyte. In all mutants the transport of molecules towards the posterior end of the egg chamber takes place as revealed by the accumulation of Bic-D or K10 transcripts. We show that the transport is ineffective in the qui and otu mutants apparently due to the lack of a properly differentiated oocyte. In the shu mutant the transport collapses and the oocyte is lost, leading to egg chambers with 15 nurse cells. We also show that one function of qui+ is to enhance otu+ mRNA expression, suggesting that these genes control the cystocyte maturation via the same pathway.
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In theory, radiographic myocardial perfusion imaging allows a quantitative assessment of the functional significance of a coronary stenosis. However, in the conventional two-dimensional projection images there does not exist a one-two-one relationship between a selected myocardial region of interest (ROI) and one particular coronary segment perfusing that area due to over-projection of myocardial regions in front of and behind the selected ROI perfused by other arterial segments, which may result in measurements which are difficult to interpret or even unreliable. To overcome these problems, we have developed two algorithms to determine the spatial distribution of perfusion levels in slices of the heart, selected approximately perpendicular to the left ventricular long axis, from two orthogonal angiographic views: the Segmental Reconstruction Technique (SRT) and the Network Programming Reconstruction Technique (NPRT). Both techniques require a priori geometric information about the myocardium, which can be obtained from the epicardial coronary tree (epicardial boundaries) and the left ventricular lumen (endocardial boundaries). Using the SRT approach, pie-shaped segments are defined for each slice within the myocardial geometric constraints such that superimposition of these segments when projected in orthogonal biplane views is minimal. The reconstruction process uses a model with identical myocardial geometry and definition of segments. Each segment of the model is assigned a relative perfusion level with unit one if no other a priori information is available. In this case, the model contains geometric information only. In case a priori information about expected segmental perfusion levels is available, a level between zero and one is assigned to each segment. The a priori information on the myocardial perfusion levels can be extracted from either anatomic information about the location and severity of existing coronary arterial obstructions, or from a slice adjacent to the one under reconstruction. Using the NPRT approach perfusion levels are computed for each volume picture element of a slice within the reconstructed myocardial geometry, thus resulting in a much higher spatial resolution than the SRT approach. A priori information of perfusion levels must be included in this approach, again based upon anatomical information, or upon the slice adjacent to the one under reconstruction. The very first slice of a myocardial study will be reconstructed by the SRT approach. Extensive computer simulations for the SRT have proved that the mean difference between the actual and reconstructed segmental perfusion levels, on a scale from 0 to 1, is smaller than 0.45 (SEE = 0.0033, REE = 1.80) for various coronary artery disease states without the use of a priori information on expected perfusion levels. This error becomes smaller than 0.36 (SEE = 0.0026, REE = 1.42), if a priori information in the reconstruction technique is included. Similar computer simulations for the NPRT have proved that these mean differences in geometric segments equal to those defined for the SRT, are smaller than 2.94 (SEE = 0.0308, REE = 0.77) on a scale from 0 to 16, without the use of a priori information on expected perfusion levels, and smaller than 1.72 (SEE = 0.0304, REE = 1.10) on the same scale when a priori information is included. Therefore, it may be concluded that slice-wise three-dimensional reconstruction of perfusion levels is feasible from biplane computer-simulated data, and that a similarity exists for mean perfusion levels in corresponding regions in the simulated and reconstructed slices, for various states of single coronary artery disease.
An isolated vagus nerve-trachea tube preparation from guinea-pig was used to study the effect kinetics of bronchodilating beta-adrenoceptor agonists. The test compounds were added either into the fluid-filled lumen or into the external medium and they all inhibited, dose-dependently and completely, the vagally induced contractions. The hydrophilic compounds isoprenaline, salbutamol and terbutaline were much less potent when administered intratracheally as compared with extratracheal administration indicating a slow transport through the epithelial layer. For the lipophilic compound, D2489 (the resorcinol derivative of salmeterol), this difference was less pronounced. When terbutaline was administered as its lipophilic diisobutyrate ester prodrug, ibuterol, the difference between the routes of administration was largely eliminated. The inhibitory effect of terbutaline, but not D2489, was readily reversed by washing. Measurements of terbutaline and D2489 in the tracheal tissue and in the external medium after the intratracheal administration of the compounds support the view that a hydrophilic compound slowly passes the epithelium and is not retained in the tissue, whereas a lipophilic compound rapidly passes the epithelium and is retained by the tissue. The isolated vagus nerve-trachea tube preparation of the guinea-pig is well suited for the concommitant study of pharmacodynamic and pharmacokinetic properties of bronchodilator drugs.
In Drosophila, the establishment of dorsoventral polarity of the developing embryo depends on the expression of at least 11 maternally acting genes. Mutant females that lack any of these gene activities produce normally shaped eggs that develop into dorsalized embryos. The female sterile K10 mutation differs from these mutants, because in addition to the dorsalized development of the embryo, it causes a dorsalization of the egg shape. During oogenesis, the K10 gene is specifically expressed in the oocyte. Antibodies raised against a beta-galactosidase-K10 fusion protein were used to visualize the K10 product in ovaries by indirect immunofluorescence. The protein, which contains a putative DNA recognition helix, accumulates in the nucleus of the oocyte, where it is assumed to have a regulatory function. Our results thus indicate that the controlled expression of some of the genes of the oocyte nucleus is essential for the determination of the dorsoventral polarity of the oocyte and possibility of the developing embryo.
The expression of the fs(1)K10 gene is required in early oogenesis for the establishment of the dorsal-ventral polarity of the oocyte, and later in the embryo. P-element-mediated transformation shows that the K10 function is located within a fragment of DNA of 5 kb, which encodes four RNA species. A major transcript of 3.1 kb is likely to be responsible for the K10 function. It is abundant in ovaries and in early developing embryos. Thus its expression profile corresponds closely to that which could be anticipated from the biological characteristics of the mutation. In situ hybridization on ovary sections shows that the gene is not only specifically transcribed in the germ line (which is consistent with the germ-line dependence of the mutation), but that its expression is also cell-specific since it is apparently restricted to the oocyte.
A method is described for the determination of delta 9-tetrahydrocannabinol-11-oic acid (delta 9-THC-11-oic acid) in urine by using a combination of liquid chromatography and glass capillary gas chromatography with electron-capture detection. Prior to extraction, the glucuronide conjugate of delta 9-THC-11-oic acid was enzymatically converted to the free acid and delta 8-THC-11-oic acid added as an internal standard. An aliquot of the extract was separated by liquid chromatography and one eluate fraction containing delta 8-THC-11-oic and delta 9-THC-11-oic acids was collected. Before gas chromatographic analysis the acids were converted to their pentafluoropropyl-pentafluoropropionyl derivatives. Authentic urine samples, positive with the EMIT cannabinoid assay, were analysed and the results compared with those obtained from an earlier described gas chromatographic-mass spectrometric method. The detection limit for the overall method was approximately 20 ng/ml. The precision was 8% for a sample concentration of 90 ng/ml of delta 9-THC-11-oic acid in urine.
Twenty-two heroin addicts admitted with an acute abdomen to the surgical department in the years 1971-1981 were reviewed. Fifteen patients had symptoms suggesting intestinal obstruction, 7 proved to have pseudo-obstruction, 4 had withdrawal symptoms, 2 had faecal impaction and only 2 had adhesions which necessitated operation. A haematocrit level of more than 0.46 was found to be indicative of true obstruction. Frequently, elevation of the white blood cell count or erythrocyte sedimentation rate merely reflected a state of accompanying soft tissue infections which were very common in these patients. The remaining 7 patients were admitted with intra-abdominal inflammation, 2 patients had an appendix mass, 1 had gonococcal peritonitis, 3 had appendicitis and 1 had a normal appendix removed. In these 7 patients the history and physical findings were characteristic of the suspected pathology.
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