Search PubMed⌕ Search

Biomedical subjects

S Hummel

Publications and source records attributed to S Hummel.

At least 55 records · Page 3Linked to original sources

Three dimensional planning target volumes: a model and a software tool.

PURPOSE: Three dimensional (3D) target volumes are an essential component of conformal therapy because the goal is to shape the treatment volume to the target volume. The planning target volume (PTV) is defined by ICRU 50 as the clinical target volume (CTV) plus a margin to ensure that the CTV receives the prescribed dose. The margin must include all interfractional and intrafractional treatment variations. This paper describes a software tool that automatically generates 3D PTVs from CTVs for lung cancers and immobile head and neck cancers. METHODS AND MATERIALS: Values for the interfractional and intrafractional treatment variations were determined by a literature review and by targeted interviews with physicians. The software tool is written in Common LISP and conforms to the specifications for shareable software of the Radiotherapy Treatment Planning Tools Collaborative Working Group. RESULTS: The tool is a rule-based expert system in which the inputs are the CTV contours, critical structure contours, and qualitative information about the specific patient. The output is PTV contours, which are a cylindrical expansion of the CTV. A model for creating PTVs from CTVs is embedded in the tool. The interfractional variation of setup uncertainty and the intrafractional variations of movement of the CTV (e.g., respiration) and patient motion are included in the model. Measured data for the component variations is consistent with modeling the components as independent samples from 3D Gaussian distributions. The components are combined using multivariate normal statistics to yield the cylindrical expansion factors. Rules are used to represent the values of the components for certain patient conditions (e.g., setup uncertainty for a head and neck patient immobilized in a mask). The tool uses a rule interpreter to combine qualitative information about a specific patient with rules representing the value of the components and to enter the appropriate component values for that patient into the cylindrical expansion formula. CONCLUSION: The portable software tool allows the rapid, consistent, and automatic generation of 3D PTVs from CTVs.

Head and Neck Neoplasms↗

Substrate specificity and expression profile of amino acid transporters (AAPs) in Arabidopsis.

Three amino acid transporter genes (AAP3-5) were isolated from Arabidopsis by complementation of a yeast mutant defective in histidine uptake. Transport is driven against a concentration gradient and sensitive to protonophores. Analysis of the substrate specificity demonstrates that the carriers have a broad substrate specificity covering the major transport forms of reduced nitrogen, i.e. glutamine and glutamate. The transporters have similar affinities for glutamate, glutamine, and alanine but differ with respect to valine, phenylalanine, histidine, arginine, and lysine. AAP3 and AAP5 efficiently transport arginine and lysine and are involved in basic amino acid transport. The predicted polypeptides of 53 kDa are highly hydrophobic with 12 putative membrane-spanning regions and show significant homologies to Arabidopsis amino acid transporters AAP1 and AAP2. Each of the genes has a different organ-specific expression in the plant. AAP3 is exclusively expressed in roots and AAP4 mainly in source leaves, stems, and flowers, whereas AAP5 is found in all tissues. The specific distribution in the plant and the different substrate specificities of AAP transporters may indicate that tissues differ both qualitatively and quantitatively regarding import or export of amino acids.

Amino Acid Sequence↗

aDNA analysis in paleopathology: mini-review and prospects.

The epidemiology of human diseases is a major indicator of living conditions. Cardiovascular diseases are said to be a phenomenon of modern industrial societies, but infectious diseases have always been an indicative determinant in historic and prehistoric human populations. The spread of infectious agents is closely related to socioeconomic factors, e.g., nutritional status, population density, and hygienic conditions. Gathering more paleoepidemiological data on infectious diseases would also be helpful in studying human adaptivity and the evolutionary capability of pathogenic microorganisms. Until now, the collection of paleoepidemiological data was restricted to those human diseases that left traces on the skeletal remains, e.g., the terminal stages of syphilis, tuberculosis, and leprosy, or degenerative disorders of the joints. With modern molecular techniques, the spectrum of detectable infectious and heritable human diseases will foreseeably be enlarged. By detecting the infectious agent, or analysing the genetic codes, it will be possible to focus systematically on those diseases that either lead to sudden death or do not affect the skeleton because of their specific course.

DNA Mutational Analysis↗

[aDNA--a new approach to old questions].

aDNA-analyses are presented for ancient bones, teeth, soft tissues and dried body fluids. The implications and perspectives for Historical Anthropology are discussed. Methods are described on examples of molecular sex determination and kinship analysis. Finally, first amplifications of DNA-sequences from pathogenes of tuberculosis and plague from ancient skeletal material are reported.

Anthropology, Physical↗

Impact of a multileaf collimator on treatment morbidity in localized carcinoma of the prostate.

PURPOSE: To evaluate the effectiveness of variable multileaf collimation, three-dimensional treatment planning, and computer-controlled conformal radiation therapy of prostate cancer. METHODS AND MATERIALS: Two hundred and forty-five patients with locally advanced prostate cancer have completed treatment over a 9-year time span using a multileaf collimator and conformal treatment techniques on the University of Washington cyclotron. All patients had three-dimensional treatment planning with computed tomography scans in the treatment position, and had treatment fields individually shaped to the target volume with a continuously variable multileaf collimator. Treatment was delivered under computer control with network transfer of the multileaf collimator settings from the treatment planning computer to the cyclotron control system. RESULTS: The multileaf collimator combined with three-dimensional treatment planning results in elegant dose distributions. These neuron dose distributions resulted in a reduced local/regional tumor failure rate with no increase in complications when compared to control treatment with photons in a randomized trial. Neutron treatment delivered at other institutions without conformal beam shaping resulted in the same improvement in local-regional tumor control rates, but was associated with a significantly higher normal tissue complication rate than seen with conformal neutron beam delivery techniques (grade 3 and 4 cumulative late normal tissue toxicity rates of 39% vs. 10%, p = 0.0007). CONCLUSIONS: Conformal treatment of prostate cancer using a multileaf collimated neutron beam results in increased local/regional tumor control rates with low normal tissue toxicities. This experience is directly applicable to the conformal treatment of prostate cancer with photons.

Humans↗

Cloning of an Arabidopsis histidine transporting protein related to nitrate and peptide transporters.

In plants, many of the proteins involved in transport of nitrogenous compounds have not been identified so far. The use of heterologous complementation in yeast mutants has enabled the isolation of a gene family encoding amino acid permease (AAP). A highly sensitive selection procedure was used to identify other proteins capable of transporting amino acids. In addition to members of the AAP gene family, an integral membrane protein (NTR1) that shows significant similarities to the low affinity nitrate transporter from Arabidpsis and to peptide transporters from yeast and rabbit was identified. NTR1 seems to be involved in the supply of reproductive organs with nitrogen as it is expressed at low levels in leaves and highly in developing pods.

Amino Acid Sequence↗

Comparison of DNA extraction and amplification from ancient human bone and mummified soft tissue.

South american precolumbian male mummies were employed as source material for a comparative investigation of bone and soft tissues by DNA analysis. The suitability of the DNA extracts from both sources was tested and evaluated by their effectiveness as target DNA in PCR amplifications. The results suggest that skeletal material should be given preference over soft tissues for PCR analysis if the material is severely degraded. This seems to be independent of the specific anatomical origin of the samples.

Anthropology, Physical↗

Expression cloning in yeast of a cDNA encoding a broad specificity amino acid permease from Arabidopsis thaliana.

To study amino acid transport in plants at the molecular level, we have isolated an amino acid permease cDNA from Arabidopsis thaliana by complementation of a yeast mutant defective in proline uptake with a cDNA. The predicted polypeptide of 53 kDa is highly hydrophobic with 12 putative membrane-spanning regions and shows no significant homologies to other known transporters. Expression of the cDNA enables the yeast mutant to take up L-[14C]proline. Competition studies argue for a broad but stereospecific substrate recognition by the permease, which resembles neutral or general amino acid transport systems from Chlorella and higher plants. Both pH dependence and inhibition by protonophores are consistent with a proton symport mechanism.

Amino Acid Transport Systems↗

Expression of the triose phosphate translocator gene from potato is light dependent and restricted to green tissues.

The export of primary photosynthesis products from chloroplasts into the cytoplasm is mediated by the triose phosphate translocator. The transporter is an integral membrane protein localized at the inner envelope of chloroplasts. In order to study the expression of the major chloroplast envelope protein gene E29, which is assumed to function as the translocator, we have isolated corresponding cDNA clones from potato. A full-length clone was sequenced and shown to be highly homologous to the E29 gene from spinach. Expression on the RNA level is restricted to green tissues, is light dependent and cannot be induced by sucrose in darkness. The presence of a single-copy gene argues for the existence of different translocator systems responsible for import and export of carbohydrates in chloroplasts and amyloplasts.

Amino Acid Sequence↗

Differential expression of two related amino acid transporters with differing substrate specificity in Arabidopsis thaliana.

A general amino acid permease cDNA (AAP2) was isolated from Arabidopsis by complementation of a yeast mutant defective in citrulline uptake. Direct transport measurements in yeast show that the protein mediates uptake of L-[14C]-citrulline and L-[14C]-proline. Detailed analyses of the substrate specificity by competition studies demonstrate that all proteogenic amino acids are recognized by the carrier, including those that represent the major transport forms of reduced nitrogen in many species, i.e. glutamine, glutamate and asparagine. Thus, AAP2 is less selective as compared with AAP1 and transports basic amino acids such as histidine as shown by expression in a histidine transport-deficient yeast strain. The predicted polypeptide of 53 kDa is highly hydrophobic with 12 putative membrane-spanning regions and shows significant homologies to the Arabidopsis broad specificity permease AAP1, and a limited homology to bacterial branched chain amino acid transporters, but not to any other known proteins. Alterations in the charged residues as compared with AAP1 in four regions might be involved in the difference in selectivity towards basic amino acids. Both genes are highly expressed in developing pods indicating a role in supplying the developing seeds with reduced nitrogen. AAP2 is selectively expressed in the stem and might therefore play a role in xylem-to-phloem transfer of amino acids during seed filling. Furthermore in situ hybridization shows that both genes are expressed in the vascular system of cotyledons in developing seedlings.

Amino Acid Sequence↗

A detailed study of the regulation and evolution of the two classes of patatin genes in Solanum tuberosum L.

The class-specific expression of patatin genes was investigated by analysing four new patatin genes. A class I patatin gene from cv. Berolina as well as a class I and two class II patatin genes from the monohaploid cultivar AM 80/5793 were isolated and partially sequenced. Sequence comparison indicates rearrangements as the major source for the generation of diversity between the different members of the classes. The expression of single genes was studied in potato plants transformed with chimaeric genes where the putative patatin promoters were fused to the GUS reporter gene. A detailed histochemical analysis reveals that both class I genes are expressed as the previously described class I patatin gene B33 from cv. Berolina [1], i.e. in the starch-containing cells of potato tubers and in sucrose-induced leaves. The class II gene pgT12 shows the same pattern as the previously described class II gene pgT2 [2], i.e. expression in root tips and in the vascular tissue of tubers, whereas no activity was detectable for pgT4. Thus the expression pattern of both classes of genes seems to be stable at least within or even between different cultivars.

Base Sequence↗

Results of neutron radiosurgery for inoperable arteriovenous malformations of the brain.

Twenty patients with inoperable arteriovenous malformations (AVMs) of the brain were treated with neutron radiosurgery. A 50 MeV cyclotron was used to deliver 9 Gy in a single fraction through 7 to 14 isocentric portals. The size and shape of the portals were customized to each treatment site. Nineteen patients have been followed for a median duration of 24 months following neutron radiosurgery. A radiographically demonstrable partial response was seen in 8 patients (42%). No complete responses were observed. There has been one post-treatment hemorrhage, no fatalities, and no evidence of radiation toxicity. The low response rate and absence of toxicity suggest that the appropriate dose for neutron radiosurgical treatment of AVMs is higher than the dose of 9 Gy at isocenter used in this initial study.

Adult↗