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Biomedical subjects

R D Larsen

Publications and source records attributed to R D Larsen.

At least 37 records · Page 2Linked to original sources
PubMed1993

Protective effects of sialylated oligosaccharides in immune complex-induced acute lung injury.

Using sialyl Lewisx (SLX) oligosaccharides derived from fucosyl transferase-expressing cells or generated synthetically, the ability of these compounds to protect against acute lung damage after deposition of immunoglobulin (Ig)G or IgA immune complexes has been determined. The synthetic compounds were tetra- and pentasaccharide derivates of SLX as well as the nonfucosylated forms of SLX as controls. In the IgG immune complex model of lung injury, which is E-selectin dependent, SLX preparations provided dose-dependent protective effects, as assessed by changes in lung vascular permeability and hemorrhage. Protective effects were associated with diminished tissue accumulation of neutrophils in lungs (as assessed by myeloperoxidase). Morphological assessment revealed reduced physical contact of neutrophils with the pulmonary vascular endothelium and reduced tissue accumulation of neutrophils. In the model of IgA immune complex-induced lung injury, which does not involve participation of neutrophils and is independent of the requirement for E-selectin, SLX preparations were not protective. These data suggest that, in neutrophil-mediated and E-selectin-dependent lung injury, SLX preparations provide significant, protective effects against inflammatory vascular injury. The ability to achieve antiinflammatory outcomes in vivo with appropriate oligosaccharides suggests a new approach to the blocking of acute inflammatory responses.

Acute Disease↗
PubMed1993

Dopamine receptors labelled by PHNO.

Since the high-affinity state of dopamine D2 receptors may be abnormal in psychomotor diseases, it is desirable to develop a radioactive agonist to label this high-affinity site for possible clinical diagnostic use. (+)PHNO is a selective D2 agonist used to treat Parkinson's disease. We prepared [3H](+)PHNO from allyl-des-propyl(+)PHNO. In binding to dopamine receptors in homogenates of canine brain striata, [3H](+)PHNO had a dissociation constant of 0.35 nM in the absence of NaCl, and 0.56 nM in the presence of NaCl. Dopamine agonists and antagonists inhibited the binding of [3H](+)PHNO at drug concentrations similar to those inhibiting other [3H]ligands at D2 receptors, but not similar to those acting at D4 receptors. Approximately 90% of the total [3H](+)PHNO binding was specific. Guanilylimidodiphosphate markedly inhibited [3H](+)PHNO binding, suggesting that [3H](+)PHNO was binding primarily to the high-affinity state of dopamine D2 receptors rather than to D3 receptors. The density of the [3H](+)PHNO binding sites was equal to that of [3H]emonapride (or [3H]YM-09151-2), both densities of which were 1.5- to 2-fold higher than that of [3H]spiperone, compatible with the idea that [3H](+)PHNO binds to monomers of D2, while [3H]spiperone binds to dimers of D2. Although [3H](+)PHNO has good selectivity and affinity for the high-affinity state of D2, the [3H]ligand was sensitive to endogenous dopamine, since washing the tissue lowered the dissociation constant. For future in vivo labelling of D2 by an agonist, therefore, it will be essential to search for a related [3H]ligand with an even lower dissociation constant.

Animals↗
PubMed1992

Isolation of a novel human alpha (1,3)fucosyltransferase gene and molecular comparison to the human Lewis blood group alpha (1,3/1,4)fucosyltransferase gene. Syntenic, homologous, nonallelic genes encoding enzymes with distinct acceptor substrate specificities.

Biochemical and genetic evidence indicates that the human genome may encode four or more distinct GDP-fucose:beta-D-N-acetylglucosaminide 3-alpha-L-fucosyltransferase (alpha(1,3)fucosyltransferase) activities. Genes encoding two of these activities have been previously isolated. These correspond to an alpha(1,3/1,4)fucosyltransferase thought to represent the human Lewis blood group locus and an alpha(1,3)fucosyltransferase expressed in the myeloid lineage. We report here the molecular cloning and expression of a third human alpha(1,3)fucosyltransferase gene, homologous to but distinct from the two previously reported human fucosyltransferase genes. When expressed in transfected mammalian cells, this gene determines expression of a fucosyltransferase capable of using N-acetyllactosamine to form the Lewis x epitope, and alpha(2,3)sialyl-N-acetyllactosamine to construct the sialyl Lewis x moiety. This enzyme shares 91% amino acid sequence identity with the human Lewis blood group alpha(1,3/1,4)fucosyltransferase, yet exhibits only trace amounts of alpha(1,4)fucosyltransferase activity. Polymerase chain reaction analyses were used to demonstrate that the gene is syntenic to the Lewis locus on chromosome 19. These analyses also excluded the possibility that this DNA segment represents an allele of the Lewis locus that encodes alpha(1,3)fucosyltransferase but not alpha(1,4)fucosyltransferase activity. These results are consistent with the hypothesis that this gene encodes the human "plasma type" alpha(1,3)fucosyltransferase, and suggest a molecular basis for a family of human alpha(1,3)fucosyltransferase genes.

Alleles↗
PubMed1991

Molecular cloning of a human fucosyltransferase gene that determines expression of the Lewis x and VIM-2 epitopes but not ELAM-1-dependent cell adhesion.

We have used the human Lewis blood group fucosyltransferase cDNA and cross-hybridization procedures to isolate a human gene that encodes a distinct fucosyltransferase. Its DNA sequence predicts a type II transmembrane protein whose sequence is identical to 133 of 231 amino acids at corresponding positions within the catalytic domain of the Lewis fucosyltransferase. When expressed by transfection in cultured cell lines, this gene determines expression of a fucosyltransferase capable of efficiently utilizing N-acetyllactosamine to form the Lewis x determinant (Gal beta 1----4[Fuc alpha 1----3]GlcNAc). By contrast, biochemical and flow cytometry analyses suggest that the enzyme cannot efficiently utilize the type II acceptor NeuNAc alpha 2----3Gal beta 1----4GlcNAc, to form the sialyl Lewis x determinant. In Chinese hamster ovary cells, however, the enzyme can determine expression of the alpha 2----3-sialylated, alpha 1----3-fucosylated structure known as VIM-2, a putative oligosaccharide ligand for ELAM-1. Cell adhesion assays using VIM-2-positive, sialyl Lewis x-negative transfected Chinese hamster ovary cells indicate that surface expression of the VIM-2 determinant is not sufficient to confer ELAM-1-dependent adhesive properties upon the cells. These results demonstrate that substantial structural similarities can exist between mammalian glycosyltransferases with closely related enzymatic properties, thus facilitating isolation of their cognate genes by cross-hybridization methods. The results further suggest that cell surface expression of the VIM-2 determinant is not necessarily sufficient to mediate ELAM-1-dependent cell adhesion.

Amino Acid Sequence↗
PubMed1990

ELAM-1--dependent cell adhesion to vascular endothelium determined by a transfected human fucosyltransferase cDNA.

Adhesion of circulating leukocytes to the vascular endothelium during inflammation is mediated in part by their interaction with the endothelial-leukocyte adhesion molecule ELAM-1. ELAM-1, a member of the LEC-CAM family of cell adhesion molecules, expresses an N-terminal carbohydrate recognition domain (CRD) homologous to various calcium-dependent mammalian lectins. However, the contribution of the CRD to cell adhesion and its carbohydrate binding specificity have not been elucidated. This study demonstrates that transfection of a human fucosyltransferase cDNA into nonmyeloid cell lines confers ELAM-1--dependent endothelial adhesion. Binding activity correlates with de novo cell surface expression of the sialylated Lewis x tetrasaccharide, whose biosynthesis is determined by the transfected fucosyltransferase cDNA. We propose that specific alpha(1,3)fucosyltransferases regulate cell adhesion to ELAM-1 by modulating cell surface expression of one or more alpha(2,3)sialylated, alpha(1,3)fucosylated lactosaminoglycans represented by the sialyl Lewis x carbohydrate determinant.

Animals↗
PubMed1990

Frameshift and nonsense mutations in a human genomic sequence homologous to a murine UDP-Gal:beta-D-Gal(1,4)-D-GlcNAc alpha(1,3)-galactosyltransferase cDNA.

We have previously isolated a murine UDP-Gal:beta-D-Gal(1,4)-D-GlcNAc alpha(1,3)-galactosyltransferase (alpha(1,3)-GT) cDNA (Larsen, R. D., Rajan, V. P., Ruff, M. M., Kukowska-Latallo, J., Cummings, R. D., and Lowe, J. B. (1989) Proc. Natl. Acad. Sci. U. S. A. 86, 8227-8231). This enzyme constructs the terminal alpha(1,3)-galactosyl linkage within the epitope Gal alpha 1----3Gal. This epitope is expressed by New World monkeys and many nonprimate mammals but generally not by Old World primates, anthropoid apes, or man. To investigate the molecular basis for the apparent species-specific absence of this enzyme and its oligosaccharide product, we have sequenced a human genomic DNA fragment homologous to the murine alpha(1,3)-GT cDNA. This fragment contains a 703-nucleotide region that shares 82% identity with a region of the murine cDNA encoding part of the enzyme's catalytic domain. The human sequence, however, has suffered deletion of single nucleotides at two separate positions, relative to the murine sequence. These frameshift mutations disrupt the translational reading frame that would otherwise maintain a 76% amino acid sequence identity between the human sequence and the murine alpha(1,3)-GT. Moreover, nonsense mutations exist within this disrupted reading frame that would truncate the human polypeptide, relative to the murine enzyme. We therefore propose that this human sequence represents a pseudogene and cannot determine expression of Gal alpha 1----3Gal epitopes on human cells.

Amino Acid Sequence↗
PubMed1990

Transfer and expression of a murine UDP-Gal:beta-D-Gal-alpha 1,3-galactosyltransferase gene in transfected Chinese hamster ovary cells. Competition reactions between the alpha 1,3-galactosyltransferase and the endogenous alpha 2,3-sialyltransferase.

The cDNA encoding a murine UDP-Gal:beta-D-Gal-alpha 1,3-galactosyltransferase has recently been cloned and sequenced using a transient expression method (Larsen, R.D., Rajan, V.P., Ruff, M.M., Kukowska-Latallo, J., Cummings, R.D., and Lowe, J.B. (1989) Proc. Natl. Acad. Sci. U.S.A. 86, 8227-8231). This report describes the construction and analysis of a Chinese hamster ovary (CHO) cell line in which in vitro expression alpha 1,3-galactosyltransferase activity has been achieved via transfer and expression of the murine alpha 1,3-galactosyltransferase gene. A primary aim of this research was to explore the role of the alpha 1,3-galactosyltransferase in regulating glycoprotein and glycolipid biosynthesis. CHO cells were cotransfected with murine genomic DNA fragments from F9 cells and plasmid DNA containing a resistance gene to the antibiotic G418. Cells resistant to G418 were then selected for expression of surface glycoconjugates containing terminal alpha 1,3-galactosyl residues by isolating cells bound to immobilized Griffonia simplicifolia-I-B4, a lectin which binds to alpha 1,3-galactosyl residues. A positive, stable transfectant clone, designated Clone 3, was obtained and analyzed for expression of the murine of alpha 1,3-galactosyltransferase. Fluorescence-activated cell sorting demonstrated that Clone 3, but not parental, CHO cells bound significant amounts of fluorescein isothiocyanate-labeled G. simplicifolia-I-B4. Southern and Northern blot analyses using the murine alpha 1,3-galactosyltransferase cDNA demonstrated that clone 3, but not parental, CHO cells contain murine alpha 1,3-galactosyltransferase genomic DNA sequences, and express a homologous transcript that comigrates with the authentic 3.6 kilobase alpha 1,3-galactosyltransferase murine mRNA. Enzyme assays confirmed that clone 3, but not parental CHO cells, contained the alpha 1,3-galactosyltransferase activity and that the level of activity is comparable to that found in F9 cells. [3H]Galactose-labeled glycopeptides and glycolipids were obtained from metabolically radiolabeled parental and Clone 3 cells and were analyzed for the presence of terminal alpha 1,3-galactosyl residues. Complex-type, Asn-linked oligosaccharides from both parental and Clone 3 cells contain the repeating disaccharide [3Gal beta 1, 4GlcNAc beta 1]n or poly-N-acetyllactosamine sequences, but only the poly-N-acetyllactosamine chains from clone 3 cells contained the terminal sequence Gal alpha 1,3Gal beta 1,4GlcNAc beta 1-R.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

Molecular cloning, sequence, and expression of a human GDP-L-fucose:beta-D-galactoside 2-alpha-L-fucosyltransferase cDNA that can form the H blood group antigen.

We have previously used a gene-transfer scheme to isolate a human genomic DNA fragment that determines expression of a GDP-L-fucose:beta-D-galactoside 2-alpha-L-fucosyltransferase [alpha(1,2)FT; EC 2.4.1.69]. Although this fragment determined expression of an alpha(1,2)FT whose kinetic properties mirror those of the human H blood group alpha(1,2)FT, their precise nature remained undefined. We describe here the molecular cloning, sequence, and expression of a human cDNA corresponding to these human genomic sequences. When expressed in COS-1 cells, this cDNA directs expression of cell surface H structures and a cognate alpha(1,2)FT activity with properties analogous to the human H blood group alpha(1,2)FT. The cDNA sequence predicts a 365-amino acid polypeptide characteristic of a type II transmembrane glycoprotein with a domain structure analogous to that of other glycosyltransferases but without significant primary sequence similarity to these or other known proteins. To directly demonstrate that the cDNA encodes an alpha(1,2)FT, the COOH-terminal domain predicted to be Golgi-resident was expressed in COS-1 cells as a catalytically active, secreted, and soluble protein A fusion peptide. Southern blot analysis showed that this cDNA identifies DNA sequences syntenic to the human H locus on chromosome 19. These results strongly suggest that this cloned alpha(1,2)FT cDNA represents the product of the human H blood group locus.

Amino Acid Sequence↗
PubMed1990

Cloning and expression of N-acetylglucosaminyltransferase I, the medial Golgi transferase that initiates complex N-linked carbohydrate formation.

This laboratory has previously identified a human gene encoding N-acetylglucosaminyltransferase I (GlcNAc-TI; EC 2.4.1.101) by complementation of the glycosylation defect in the Lec1 Chinese hamster ovary (CHO) cell mutant. A phage lambda library prepared from genomic DNA of a tertiary Lec1 transfectant (3 degrees T) has now been used to obtain clones encoding an active GlcNAc-TI enzyme. A small genomic DNA fragment [approximately 4.6 kilobases (kb)], isolated from an Alupositive lambda clone, conferred human GlcNAc-TI activity upon transfection into Lec1 cells. An approximately 1.3-kb probe generated from this DNA fragment detected unique but distinct DNA fragments in human and CHO genomic DNA. The probe also hybridized to a poly(A)+ RNA of approximately 2.7 kb in human and CHO cells and allowed the isolation of a full-length cDNA encoding human GlcNAc-TI activity. The overall features of the cDNA and deduced protein sequence (445 amino acids) are typical of other Golgi transferases that are type II transmembrane proteins. Northern blot analysis with the same probe showed that Lec1 mutant cells also possessed an approximately 2.7-kb poly(A)+ RNA, indicating that the lec1 mutation is a point mutation.

Amino Acid Sequence↗
PubMed1990

A cloned human cDNA determines expression of a mouse stage-specific embryonic antigen and the Lewis blood group alpha(1,3/1,4)fucosyltransferase.

The stage-specific embryonic antigen SSEA-1 is a cell-surface oligosaccharide molecule expressed with temporal precision during the murine preimplantation period and implicated in adhesive events involving the process of compaction. We used a mammalian transient expression system to isolate a cloned human cDNA that determines expression of the SSEA-1 molecule. The cDNA sequence predicts a type II transmembrane protein with a domain structure similar to mammalian glycosyltransferases, but without primary sequence similarity to these enzymes. The carboxy-terminal domain of this protein was shown to be catalytically active as a fucosyltransferase when expressed in COS-1 cells as a portion of a secreted protein A fusion peptide. The enzyme is an exceptional glycosyltransferase in that it can use both type I and type II oligosaccharides as acceptor substrates to generate subterminal Fuc alpha(1,4)- and Fuc alpha(1,3)-linkages, respectively, in a manner analogous to the human Lewis blood group fucosyltransferase. Southern blot analysis shows that the cDNA corresponds to sequences syntenic to the Lewis locus on chromosome 19. These results indicate that this cDNA is the product of the human Lewis blood group locus, provide genetic confirmation of the hypothesis that this enzyme can catalyze two distinct transglycosylation reactions, and outline an approach to the isolation of other sequences that determine expression of developmentally regulated oligosaccharide antigens.

Amino Acid Sequence↗
PubMed1989

A cloned human DNA restriction fragment determines expression of a GDP-L-fucose: beta-D-galactoside 2-alpha-L-fucosyltransferase in transfected cells. Evidence for isolation and transfer of the human H blood group locus.

We have described previously a gene transfer system for the isolation of human DNA sequences that determine expression of a mammalian GDP-fucose: beta-D-galactoside-2-alpha-L-fucosyltransferase (alpha-(1,2)-fucosyltransferase) (Ernst, L. K., Rajan, V. P., Larsen, R. D., Ruff, M. M., and Lowe, J. B. (1989) J. Biol. Chem. 264, 3436-3447). With this system, we found that de novo expression of the fucosyltransferase in mouse recipient cells was associated with the transfer and stable genomic integration of characteristic human DNA restriction fragments. We report here the results of experiments designed to determine the genetic origin of the fucosyltransferase determined by these sequences. First, we characterize the fucosyltransferases found in these mouse transfectants and in the human cell line used as a DNA donor. We compare their properties to those displayed by the human H and Secretor blood group fucosyltransferases. We find that the enzymes in the transfected cells have properties similar or identical to those of the human H alpha-(1,2)-fucosyltransferase. However, their properties differ significantly from the properties of the human Secretor alpha-(1,2)-fucosyltransferase and are also distinct from the properties of a murine alpha-(1,2)-fucosyltransferase. To confirm further that these transfected human sequences determine the H phenotype of the transfectants, we cloned the two human EcoRI restriction fragments common to each H-expressing secondary transfectant. The larger of these two fragments directs de novo expression of an alpha-(1,2)-fucosyltransferase when transfected into COS-1 cells. The pH activity profile of this alpha-(1,2)-fucosyltransferase and its apparent Michaelis constants for substrate and acceptor mirror those we determined for the human H alpha-(1,2)-fucosyltransferase. We conclude that genetic information sufficient to determine expression of this alpha-(1,2)-fucosyltransferase resides within the 3.4-kilobase pair human EcoRI restriction fragment and that this most likely represents the human H blood group locus.

ABO Blood-Group System↗
PubMed1989

Stable expression of blood group H determinants and GDP-L-fucose: beta-D-galactoside 2-alpha-L-fucosyltransferase in mouse cells after transfection with human DNA.

We report here the application of a genetic approach to identify and isolate human DNA sequences controlling the expression of a GDP-L-fucose: beta-D-galactoside 2-alpha-L-fucosyltransferase [alpha-1,2)fucosyltransferase). Mouse L cells were chosen as host cells for this scheme since they express the necessary substrate and acceptor molecules for surface display of blood group H Fuc alpha 1----2 G al linkages constructed by (alpha-1,2) fucosyltransferases. However, they do not express cell surface blood group H structures nor detectable (alpha-1,2)fucosyltransferase activity. We therefore asked if (alpha-1,2)fucosyltransferase activity could be expressed and detected in these cells after transfection with human DNA sequences. These cells were transfected with genomic DNA isolated from a human cell line (A431) that expresses (alpha-1,2)fucosyltransferase. A panning procedure and fluorescence-activated cell sorting were used to isolate a mouse transfectant cell line that expresses cell surface H Fuc alpha 1----2 Gal linkages and a cognate (alpha-1,2)fucosyltransferase. Southern blot analysis showed that the genome of this cell line contains several hundred kilobase pairs of human DNA. Genomic DNA from this primary transfectant was used to transfect mouse L cells, and several independent, H-expressing secondary transfectants were isolated by immunological selection. Each expresses an (alpha-1,2)fucosyltransferase. Southern blot analysis demonstrated that the genome of each secondary transfectant contains common, characteristic human DNA restriction fragments. These results show that transfected human DNA sequences determine expression of the (alpha-1,2)fucosyltransferases in the mouse transfectants, that these sequences represent a single locus, and that they are within or linked to specific human restriction fragments identifiable in each secondary transfectant. These sequences may represent a human (alpha-1,2)fucosyltransferase gene.

ABO Blood-Group System↗
PubMed1989

Development of molecular approaches to estimating germinal mutation rates. I. Detection of insertion/deletion/rearrangement variants in the human genome.

DNA from 130 individuals was studied with up to 18 (primarily cDNA) probes for the frequency of variants in this initial experiment to determine the feasibility of this approach to screening for germinal gene mutations. This approach, a modification of the usual restriction enzyme mapping strategy, focuses on the detection of insertion/deletion/rearrangement (I/D/R) variants, because the DNA is digested with only two restriction enzymes before transfer to membranes and hybridization with an extensive series of unrelated probes. Some 4000 noncontiguous, independent DNA fragments ("loci"), functional loci, pseudogenes or anonymous fragments, (a total of approximately 77,400 kb) were screened. 19 different classes and 31 copies of presumably I/D/R variants were detected while 4 different classes and 24 individuals exhibiting base substitution variants were observed. 18 of the 19 I/D/R classes were rare variants, that is, each were observed at a frequency, within this population, of less than 0.01; 3 of the base substitution classes existed at polymorphic frequencies and only 1 was a rare variant. 10 of the I/D/R classes, occurring in a total of 18 individuals, were detected with probes which are not known to be associated with repetitive elements. This is a variant frequency for I/D/R variants without known repetitive elements of 0.15 classes and 0.23 copies for each 1000 kb screened; this would extrapolate to 1600 such variant sites in the genome of each individual. Within the context of a mutation screening program, the rare variants, either with or without repetitive elements, would have a higher probability of being de novo mutations than would polymorphic variants; this former group would be the focus of family studies to test for the heritability of the allele (fragment pattern). Sufficient DNA probes are available to screen a significant portion of the human genome for genetic variation and de novo mutations of this type.

Blotting, Southern↗
PubMed1989

Monitoring and evaluation in an Army health clinic.

In 1987, the authors implemented an indicator monitoring system that allows for ongoing evaluation of important aspects of care at the Erlangen Health Clinic, Erlangen, Federal Republic of Germany, a U.S. Army primary medical clinic serving approximately 1,200 patients a month. Staff developed prospective and retrospective indicators based on identified high-risk, high-volume areas, and established thresholds of evaluation for each of the indicators. A numerical auditing mechanism is used to record compliance with established objective criteria that determine whether or not a case is deficient. A peer review committee reviews and recommends actions for deficient cases.

Ambulatory Care Facilities↗
PubMed1989

Isolation of a cDNA encoding a murine UDPgalactose:beta-D-galactosyl- 1,4-N-acetyl-D-glucosaminide alpha-1,3-galactosyltransferase: expression cloning by gene transfer.

We have developed a genetic approach to isolate cloned cDNA sequences that determine expression of cell surface oligosaccharide structures and their cognate glycosyltransferases. A cDNA library was constructed in a mammalian expression vector by using mRNA from a murine cell line known to express a UDPgalactose:beta-D-galactosyl-1,4-N-acetyl-D-glucosaminide alpha-1,3-galactosyltransferase [(alpha 1-3)GT; EC 2.4.1.151]. This library was transfected into COS-1 cells, which lack expression of (alpha 1-3)GT. Transfected cells containing functional (alpha 1-3)GT cDNAs were detected and isolated with a lectin that recognizes the surface-expressed glycoconjugate product of the (alpha 1-3)GT enzyme. One cloned (alpha 1-3)GT cDNA was rescued from lectin-positive transfected cells. This cDNA contains a single long open reading frame that predicts a 394-amino-acid protein. No significant primary structure similarities were identified between this protein and other known sequences. However, the protein predicts a type II transmembrane topology similar to two other mammalian glycosyltransferases. This topology places the large COOH-terminal domain within the Golgi lumen; this domain was shown to be catalytically active when expressed in COS-1 cells as a portion of a secreted protein A fusion peptide. Biochemical analysis confirmed that this enzyme catalyzes a transglycosylation reaction between UDP-Gal and Gal(beta 1-4)GlcNAc to form Gal(alpha 1-3)Gal(beta 1-4)GlcNAc. This cloning approach may be generally applicable to the isolation of cDNAs encoding other mammalian glycosyltransferases.

Amino Acid Sequence↗
PubMed1988

Transmetacarpal amputations and replantation: the importance of the normal vascular anatomy.

Three transmetacarpal injuries are described in which the patency of one common digital vessel alone provided blood flow to all fingers. Transverse commissural vessels connect the digital vessels proximal to the proximal and distal interphalangeal joints. Retrograde flow to the adjacent common digital vessels revascularises the other digits. The volar metacarpal vessels, if not ligated, may allow continued bleeding into the palm following reattachment of a transmetacarpal amputation. These vessels may have been responsible for failure of the replantation in one case.

Adult↗
PubMed1987

Practice of 3-dimensional treatment planning at the Fox Chase Cancer Center, University of Pennsylvania.

The use of 3-dimensional (3-D) dose distributions and dose-volume histograms in radiation therapy treatment planning is illustrated on a patient with a head and neck tumor. The patient was immobilized in a rectangular tissue compensation bolus box. The treatment was planned with a 14 MeV D-T derived fast neutron therapy beam. The isodose distributions and the dose-volume histograms at multiple adjacent levels are used to evaluate the adequacy of coverage of target volumes and the doses to the normal tissues. Such dose-volume histograms are useful and practical in summarizing the dose distribution throughout the irradiated volume, assessing the degree of uniformity of the dose distribution within the target volume, quantifying the amount of normal tissue irradiated, and evaluating rival treatment plans for both particle and nonparticle beams.

Fast Neutrons↗