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Biomedical subjects

J D Hall

Publications and source records attributed to J D Hall.

At least 37 records · Page 2Linked to original sources

Bandeau--the focal point of frontocranial remodeling.

Reconstructing the proper balance and harmony of the face begins with the manipulation and positioning of the bandeau. The bandeau or brow is the key architectural component of craniofacial reconstruction. Advancement of the supraorbital bar and forehead can result in functional improvements. This article details the historical development of the surgical procedures available for use in recontouring the forehead. Specific surgical procedures are described and evaluated including the method of removing an unsuitable, unusable bandeau, fashioning a new one from a strip of parietal cranial bone, and repositioning it. The advantages of the bilateral lamellar split bandeau are discussed.

Adult↗

Characterization of a major DNA-binding domain in the herpes simplex virus type 1 DNA-binding protein (ICP8).

We have studied the major DNA-binding protein (ICP8) from herpes simplex virus type 1 to identify its DNA-binding site. Since we obtained our protein from a cell line carrying multiple chromosomally located copies of the ICP8 gene, we first analyzed this protein to assess its similarity to the corresponding viral protein. Our protein resembled the viral protein by molecular weight, response to antibody, preference for binding single-stranded DNA, and ability to lower the melting temperature of poly(dA-dT). To define the DNA-binding domain, we subjected the protein to limited trypsin digestion and separated the peptide products on a sodium dodecyl sulfate-polyacrylamide gel. These fragments were then transferred to a nitrocellulose membrane, renatured in situ, and tested for their ability to bind DNA. From this assay, we identified four fragments which both bound DNA and exhibited the expected binding preference for single-stranded DNA. The sequence of the smallest of these fragments was determined and corresponds to a polypeptide spanning residues 300 to 849 in the intact protein. This peptide contains several regions which may be important for DNA binding based on sequence similarities in single-stranded DNA-binding proteins from other herpesviruses and, in one case, on a conserved sequence found in more distant procaryotic and eucaryotic proteins.

Amino Acid Sequence↗

Inventory auditing: a manufacturing perspective.

Despite the mystery that usually surrounds the annual audit program, its plan is easy to understand if you learn the basic concerns of the auditor. A five-step inventory audit plan usually consists of proving that the inventory exists, is completely represented, belongs to the firm, is properly valued, and is properly classified. To develop the inventory audit plan, an auditor must verify a firm's system of internal controls, in addition to verifying management's financial assertions by obtaining evidence about them. The time, cost, and frequency of the inventory audit with even the best plans may vary because of changing factors.

Accounting↗

Aphidicolin resistance in herpes simplex virus type I reveals features of the DNA polymerase dNTP binding site.

We describe the mapping and sequencing of mutations within the DNA polymerase gene of herpes simplex virus type 1 which confer resistance to aphidicolin, a DNA polymerase inhibitor. The mutations occur near two regions which are highly conserved among DNA polymerases related to the herpes simplex enzyme. They also occur near other herpes simplex mutations which affect the interactions between the polymerase and deoxyribonucleoside triphosphate substrates. Consequently, we argue in favor of the idea that the aphidicolin binding site overlaps the substrate binding site and that the near-by conserved regions are functionally required for substrate binding. Our mutants also exhibit abnormal sensitivity to another DNA polymerase inhibitor, phosphonoacetic acid. This drug is thought to bind as an analogue of pyrophosphate. A second-site mutation which suppresses the hypersensitivity of one mutant to phosphonoacetic acid (but not its aphidicolin resistance) is described. This second mutation may represent a new class of mutations, which specifically affects pyrophosphate, but not substrate, binding.

Amino Acid Sequence↗

Sternal osteomyelitis: treatment with rectus abdominis muscle.

Sternal osteomyelitis complicates recovery in a small number of patients following median sternotomy. Techniques for operative treatment have in common the wide debridement of devitalised tissue and administration of culture-specific antibiotics. The resultant wound can be managed by delayed primary closure or transposition of well-vascularised adjacent tissue. Omentum, pectoralis major muscle and rectus abdominis muscle are suitable for transposition either alone or in combination. Our series is composed of ten patients who underwent rectus abdominis muscle transfer for the treatment of sternal osteomyelitis. The rectus abdominis obliterates dead space in the lower third of the wound, a difficult area to reach with the pectoralis major muscle. Five patients had one rectus abdominis muscle alone transposed, avoiding the aesthetic and functional deficits of pectoralis major transposition and the risks of omental transfer. Wound healing occurred in every case with a minimum of postoperative complications.

Abdominal Muscles↗

Conchal cartilage and composite grafts for correction of lower lid retraction.

Lower eyelid retraction may be due to vertical deficiency of the anterior lamella, supporting cartilage, or posterior lamella. We have used autologous cartilage grafts from the conchal bowl for reconstruction of the central lamella, reestablishing and augmenting support of the lower lid. The positioning of the graft is dependent on the specific anatomic deficiency, and the etiology of the lid retraction must be carefully evaluated. In patients with posterior lamella deficiency, the contracted lower lid retractors and conjunctiva are released and the graft is placed facing the bulbar conjunctiva and is allowed to reepithelialize. In patients in whom there is an associated skin deficiency, composite auricular grafts are used. We present our experience in 33 patients with lower lid retraction. Twenty-three patients required placement of a cartilage graft only, while 10 patients had an associated skin deficiency requiring placement of composite cartilage. In nine patients the cartilage graft was seated against the bulbar conjunctiva and allowed to reepithelialize. Reepithelialization was complete within 3 1/2 weeks in all but two of these patients. This technique has provided stable lid support in all 33 patients.

Adolescent↗

A software tool for finding locally optimal alignments in protein and nucleic acid sequences.

We describe software for aligning protein or nucleic acid sequences based on the concept of match density. This method is especially useful for locating regions of short similarity between two longer sequences which may be largely dissimilar (e.g. locating active site regions in distantly related proteins). Our software is able to identify biologically interesting similarities between two sub-regions because it allows the user to control the matching parameters and the manner in which local alignments are selected for display. Furthermore, the collection and ranking of alignments for display uses a novel, highly efficient algorithm. We illustrate these features with several examples. In addition, we show that this tool can be used to find a new conserved sequence in several viral DNA polymerases, which, we suggest, occurs at a functionally important enzymatic site.

Algorithms↗

Congenital ear deformity: reconstruction using composite graft.

We present a congenital deformity of the right ear, characterized by absence of the central portion of the helix and antihelix. The deformity was reconstructed by advancing retroauricular skin and closing the resultant defect with a composite graft from the posterior aspect of the left ear. This technique was performed in a single stage and required no incisions on the anterior surface of either ear. Postoperative appearance of the right ear was satisfactory, and donor deformity was minimal.

Cartilage↗

Using a monoclonal antibody to identify patients with type I and type II von Willebrand's disease.

Three monoclonal antibodies produced against vWF:Ag by conventional hybridoma technique did not inhibit factor VIII coagulant activity (F. VIII:C) but did inhibit VIII ristocetin cofactor activity. The antibodies were used in an indirect competitive ELISA for quantifying von Willebrand's antigen (vWF:Ag) and compared with values obtained by the Laurell technique using commercial antibody by means of a ratio: ELISA/Laurell. For one monoclonal BD2-CC9, vWF:Ag values obtained in the two assays were in good agreement for normal and hemophilia A plasmas (normal, n = 19, ratio = 1.13 +/- .17, hemophilia A, n = 10, ratio = 0.91 +/- .15). However, type II vWD patients had a disproportionately low value of vWF:Ag with the ELISA. Use of the ratio normalized the difference among individual plasma values and allowed a significant separation of type II vWD plasma (n = 9, ratio = 0.46 +/- .19) from normal plasma (p = .0001) and type I vWD plasma (n = 8, ratio = 1.52 +/- .34) from type II vWD plasma (p = .0003) using BD2-CC9. Although the sample size was small, the greater degree of discrimination among the vWD plasmas tested with BD2-CC9 (compared with the other two antibodies [CA3-AE4, CC6-BG10]) suggests that this antibody may recognize conformational epitopes that reflect the degree of multimeric polymerization of the vWF molecule rather than simply recognize a decreased number of antigenic sites in a basic subunit. BD2-CC9 may be valuable in investigating the various types of vWD and/or the process of polymerization of this complex protein.

Antibodies, Monoclonal↗

Incidence and transfer of R-plasmids at a hospital in Saudi Arabia.

One hundred and fifty Gram-negative bacteria isolated from patient specimens at King Faisal Specialist Hospital were examined for their ability to transfer antibiotic resistance plasmids to a sensitive Escherichia coli recipient in conjugation and transformation experiments. Agarose gel electrophoresis was used to enumerate and size the R-plasmids found, and Southern DNA hybridization was used to assess similarities between antibiotic resistance plasmids from different bacteria and sources. Of the bacterial isolates tested 65% contained plasmids, 70% of these transferred antibiotic resistance to E. coli, and 40% transferred multiple, linked resistances on R-plasmids. DNA hybridization of these R-plasmids demonstrated widespread similarities between plasmids from different bacterial genera and from different hospital locations. In particular, a gene encoding ampicillin resistance appeared especially widespread, indicating that a transposon may be mediating transmission of this resistance.

Conjugation, Genetic↗

Structural organization and unusual codon usage in the DNA polymerase gene from herpes simplex virus type 1.

We have analyzed the protein and nucleic acid sequences of the DNA polymerase from herpes simplex virus type 1 (HSV-1) to provide insight into the expression and possible structure of this enzyme. Extensive similarity between the amino acid sequence and that of the Epstein Barr virus DNA polymerase is reported. We describe probable structural similarities between these proteins and the use of these similarities to define structural and functional domains within the polymerase. Analysis of base composition and codon usage reveals that several genes from HSV-1, including DNA polymerase, exhibit a strong preference for guanine or cytosine at the third codon position. This preference may result from the high guanine + cytosine content of the virus and produces a highly restricted codon usage, different from that of the host cell. Consequences of the unusual codon usage for viral expression include the potential for extensive mRNA secondary structure.

Amino Acid Sequence↗

Reduced in vivo mutagenesis by mutant herpes simplex DNA polymerase involves improved nucleotide selection.

We present evidence that mutation frequencies in a mammalian system can vary according to the replication fidelity of the DNA polymerase. We demonstrated previously that several derivatives of herpes simplex virus type 1 that encode polymerases resistant to various antiviral drugs (e.g., nucleotide analogues) also produce reduced numbers of spontaneous mutants. Here we show that the DNA polymerase from one antimutator virus exhibits enhanced replication fidelity. First, the antimutator virus showed a reduced response to known mutagens that promote base mispairing during DNA replication (N-methyl-N'-nitro-N-nitrosoguanidine, 5-bromo-deoxyuridine). Second, purified DNA polymerase from the antimutator produced fewer replication errors in vitro, based on incorporation of mispaired nucleotides or analogues with abnormal sugar rings. We have investigated possible mechanisms for the enhanced fidelity of the antimutator polymerase. We show that the mutant enzyme has altered interactions with nucleoside triphosphates, as indicated by its resistance to nucleotide analogues and elevated Km values for normal nucleoside triphosphates. We present evidence against increased proofreading by an associated 3',5' exonuclease (as seen for T4 bacteriophage antimutator polymerases), based on nuclease levels in the mutant polymerase. We propose that reduced affinity of the polymerase for nucleoside triphosphates accounts for the antimutator phenotype by accentuating differences in base-pair stability, thus facilitating selection of correct nucleotides.

Alkylation↗

Sequence and mapping analyses of the herpes simplex virus DNA polymerase gene predict a C-terminal substrate binding domain.

The herpes simplex virus DNA polymerase provides an excellent model for studies of eukaryotic replicative polymerases. We report here the nucleotide sequence of the gene which encodes this enzyme. The gene includes a 3705-base-pair major open reading frame capable of encoding a Mr 136,519 polypeptide, in rough agreement with previous estimates of the size of the major polypeptide found in partially purified viral polymerase preparations. The predicted polymerase polypeptide shares extensive sequence homology with the Epstein-Barr virus open frame predicted to encode DNA polymerase and with a 13-amino acid segment of adenovirus 2 DNA polymerase. Mutations conferring altered sensitivity to antiviral deoxynucleoside triphosphate analogs, pyrophosphate analogs, or aphidicolin from eight different mutants map within the region encoding the carboxyl-terminal portion of the predicted polymerase polypeptide. Two of these are separated by a distance corresponding to at least 228 amino acids. We propose that this region of the gene encodes a polypeptide domain that contains the binding sites for deoxynucleoside triphosphates and pyrophosphate.

Amino Acid Sequence↗

When should nerve gaps be grafted? An experimental study in rats.

In conclusion, animal experiments have shown the following: (1) extensive elevation (mobilization) of a nerve from its bed does not interfere with its capacity to regenerate as long as the longitudinal epineural vessels are preserved, (2) suturing nerve ends under tension has a deleterious effect on the final results, (3) when a segment of nerve has been resected, the remaining nerve and the site of repair can lengthen to accommodate joint extension (within limitations), (4) if there is a segmental loss of nerve and if the nerve ends can be approximated with 10-0 epineural sutures, even if the joints must be fully flexed, the result is better than using a nerve graft, and (5) when a graft is required, it is important to avoid reversing the nerve graft. We believe direct nerve repair is preferred when flexion of the joints and mobilization of the nerve ends permits approximation with 10-0 epineural suture.

Animals↗

Isolation of an organism resembling Clostridium barati which produces type F botulinal toxin from an infant with botulism.

All reported cases of infant botulism except one have been caused by proteolytic strains (group I) of Clostridium botulinum, toxin types A or B. We describe the cultural and biochemical characteristics of the causative organism of this singular case of infant botulism, caused by type F botulinal toxin. Although this organism produces type F botulinal toxin, it is quite different from proteolytic (group I) C. botulinum, being more closely related to Clostridium barati.

Botulinum Toxins↗

Generation of genetic diversity in herpes simplex virus: an antimutator phenotype maps to the DNA polymerase locus.

We have measured the spontaneous production of mutants in derivatives of herpes simplex virus type 1 resistant to phosphonoacetic acid. Six such derivatives produced 9- to 123-fold fewer iododeoxycytidine (ICdR-)-resistant progeny (i.e., thymidine kinase deficient) than their wild-type parents. To locate the mutation which controls mutant production in one of the strains (PAAr-5), we constructed phosphonoacetic acid-resistant, recombinant viruses by marker transfer, using wild-type viral DNA and DNA restriction fragments conferring the resistance phenotype. The resultant recombinants also produced very low levels of ICdR-resistant progeny during growth, indicating a close linkage (within 1.1 kilobase pairs) between the drug resistance locus and the sequences controlling production of mutant progeny. Evidence is presented that the low mutant yield in PAAr-5 is not due to abnormal expression of mutants, hypersensitivity to ICdR, altered thymidine kinase activity, or slow replication rates. Since the locus conferring resistance to phosphonoacetic acid in PAAr-5 has been shown previously to be the DNA polymerase gene, we hypothesize that the reduced yield of mutants results from enhanced replication fidelity by the altered DNA polymerase. The existence of antimutator derivatives of herpes simplex indicates that the observed high mutation rate for wild-type strains is an intrinsic property of the virus and may provide a selective advantage during growth in animal hosts.

Cell Line↗