PubMed HealthSearch

Biomedical subjects

M M Smith

Publications and source records attributed to M M Smith.

At least 19 recordsLinked to original sources

Clinical evaluation of axial pattern skin flaps in dogs and cats: 19 cases (1981-1990).

Nineteen axial pattern skin flaps were used in 16 dogs and cats to provide skin for repair of extensive cutaneous defects. Retrospective evaluation of medical records was used to determine percentage flap survival, postoperative complications, and long-term outcome of axial pattern skin flaps. The most common indication for use of axial pattern flaps was to augment wound closure following tumor resection (n = 7). Other indications included trauma (n = 5), chronic nonhealing wounds (n = 4), urine-induced cellulitis (n = 1), idiopathic dermal necrosis (n = 1), and chronic lymphoplasmocytic dermatitis (n = 1). Mean flap survival (+/- SD) was 96% (+/- 8). Postoperative complications included wound drainage (n = 15), partial dehiscence of the sutured flap (n = 7), distal flap necrosis (n = 6), infection (n = 3), edema (n = 3), and seroma formation (n = 2). After a median follow-up time of 5 months, evaluation of animals indicated that surgery provided successful wound reconstruction with good cosmetic results. Reconstruction of large cutaneous defects is facilitated by axial pattern flap application regardless of cause of wound. Postoperative complications are common but amenable to standard wound management techniques such as drain placement and surgical debridement of devitalized distal flap skin.

Animals

Evaluation of biocompatible osteoconductive polymer as an orthopedic implant in dogs.

The biocompatibility and osteoconductive properties of biocompatible osteoconductive polymer (BOP), a synthetic implant, were evaluated. Bilateral oval cortical defects (1 x 2 cm) were made in the lateral subtrochanteric area of the proximal portion of the femur in 16 dogs that later were treated with BOP fiber (n = 16) or autogenous cancellous bone (n = 11), or were not treated (n = 5). The BOP block was attached extraperiosteally to the proximal portion of the humerus in 6 dogs. Radiographic assessment of surgery sites was performed at 4-week intervals, and histologic evaluation was performed at 4, 8, 16, and 24 weeks after surgery. Radiographic signs of bone healing were not observed in defects treated with BOP fiber. Defects treated with cancellous bone or not treated had radiographic signs of progressive bone ingrowth. Radiographic evidence of periosteal new bone formation near control and BOP-treated defects was observed 4 weeks after surgery; increased periosteal reaction was associated with BOP fiber. This new bone had resorbed by week 24, except bone adjacent to BOP fiber, where continued periosteal reaction was apparent. Histologic evidence of bone formation was observed extending to, but not incorporating, BOP fibers. The BOP fibers became surrounded by a fibrous capsule, and fibrovascular connective tissue infiltrated between and into BOP fibers, but minimal bone formation incorporated the BOP material during the follow-up period. During that time, active periosteal new bone formation was evident adjacent to the BOP fibers. Defects treated with cancellous bone or not treated healed by ingrowth of cancellous bone during the first 12 weeks after surgery and by reformation of the lateral cortical wall by week 24. The BOP blocks became surrounded by a fibrous capsule, but connective tissue or bone ingrowth into BOP blocks was not observed. Results indicate that BOP is not osteoconductive within a 6-month time frame when used in subtrochanteric femoral defects or when placed extraperiosteally on the proximal portion of the humerus of clinically normal dogs.

Animals

Presence of the earliest vertebrate hard tissue in conodonts.

From histological investigations into the microstructure of conodont elements, a number of tissue types characteristic of the phosphatic skeleton of vertebrates have been identified. These include cellular bone, two forms of hypermineralized enamel homologs, and globular calcified cartilage. The presence of cellular bone in conodont elements provides unequivocal evidence for their vertebrate affinities. Furthermore, the identification of vertebrate hard tissues in the oral elements of conodonts extends the earliest occurrence of vertebrate hard tissues back by around 40 million years, from the Middle Ordovician (475 million years ago) to the Late Cambrian (515 million years ago).

Animals

Hepatitis E virus (HEV): strain variation in the nonstructural gene region encoding consensus motifs for an RNA-dependent RNA polymerase and an ATP/GTP binding site.

Hepatitis is transmitted by a number of infectious agents. The epidemiological characterization of waterborne or enterically transmitted non-A, non-B hepatitis (ET-NANBH) is unique when compared with other known hepatitides. We have reported on the molecular cloning of a cDNA clone derived from the etiologic agent associated with ET-NANBH, the hepatitis E virus (HEV). The complete sequence of these first molecular clones, isolated from an HEV-infected human after passage in Macaca fascicularis (cynomolgus macaques), illustrates a distant relationship to other known positive-strand RNA viruses of plants and animals. The translated major open reading frame (ORF-1) from these clones indicates that this portion of the genome encodes a polyprotein with consensus sequences found in RNA-dependent RNA polymerase and ATP/GTP binding domains. The latter activity has been associated with putative helicases of positive-strand RNA viruses. These viral-encoded enzymatic activities identify this region and ORF-1 as containing at least two different nonstructural genes involved in HEV replication. Molecular clones obtained from two other geographically distinct HEV isolates demonstrated sequence heterogeneity in this nonstructural gene region. Further study will be required to elucidate the pathogenic significance (if any) of this observed divergence in the nonstructural region.

Adenosine Triphosphate

Histone H3 transcription in Saccharomyces cerevisiae is controlled by multiple cell cycle activation sites and a constitutive negative regulatory element.

The promoters of the Saccharomyces cerevisiae histone H3 and H4 genes were examined for cis-acting DNA sequence elements regulating transcription and cell division cycle control. Deletion and linker disruption mutations identified two classes of regulatory elements: multiple cell cycle activation (CCA) sites and a negative regulatory site (NRS). Duplicate 19-bp CCA sites are present in both the copy I and copy II histone H3-H4 promoters arranged as inverted repeats separated by 45 and 68 bp. The CCA sites are both necessary and sufficient to activate transcription under cell division cycle control. A single CCA site provides cell cycle control but is a weak transcriptional activator, while an inverted repeat comprising two CCA sites provides both strong transcriptional activation and cell division cycle control. The NRS was identified in the copy I histone H3-H4 promoter. Deletion or disruption of the NRS increased the level of the histone H3 promoter activity but did not alter the cell division cycle periodicity of transcription. When the CCA sites were deleted from the histone promoter, the NRS element was unable to confer cell division cycle control on the remaining basal level of transcription. When the NRS element was inserted into the promoter of a foreign reporter gene, transcription was constitutively repressed and did not acquire cell cycle regulation.

Base Sequence

Problems in deterrence: a comparison of the driving histories of DUII and non-DUII drivers.

Driving records of subjects arrested for driving under the influence of intoxicants (DUII), both recidivists and nonrecidivists, were compared with records of an age- and sex-matched random sample of non-DUII drivers. Major differences were found between DUII and non-DUII groups in the incidence of traffic violations but some differences also existed between nonrecidivist and recidivist DUII subjects. Rehabilitative diversion programs for first-time DUII offenders did not affect recidivism rates in the study population. Findings in this study suggest that general deterrence directed at the non-DUII population should receive emphasis equal to specific deterrence directed at DUII offenders.

Accidents, Traffic

Evaluation of the proximal portion of the femur as an autogenous cancellous bone donor site in dogs.

The proximal portion of the femur was evaluated as a source of autogenous cancellous bone in dogs. Bilateral oval cortical defects were created in the lateral subtrochanteric area of the femur in 16 dogs. Cancellous bone was removed and the weight recorded. Cancellous bone was similarly harvested from the proximal portion of the humerus in 7 of these dogs. Subtrochanteric femoral defects in 11 dogs were randomly assigned to receive cancellous bone graft obtained from the femur (n = 4) or the humerus (n = 7). Subtrochanteric defects in 5 dogs were not grafted. Radiographic assessment of subtrochanteric defects was performed at 4-week intervals, and histologic assessment at 4, 8, 16, and 24 weeks after surgery. Nongrafted donor sites healed by ingrowth of trabecular bone during the first 12 weeks after surgery. By week 24, the lateral cortical wall had reformed, but remodeling was incomplete. Donor sites grafted with cancellous bone healed similarly, but with more rapid healing and more complete remodeling evident by week 24. Although the mean weight of cancellous bone harvested from the proximal portion of the femur (0.82 +/- 0.22 g) was significantly (P less than 0.05) less than that harvested from the proximal portion of the humerus (1.38 +/- 0.29 g), there was no qualitative histologic or radiographic difference in bony healing of grafted defects. We determined that the proximal portion of the femur can be safely used to provide moderate amounts of cancellous bone, and that a second bone graft can be collected from the same subtrochanteric donor site after 12 weeks.

Animals

High affinity block of myocardial L-type calcium channels by the spider toxin omega-Aga-toxin IIIA: advantages over 1,4-dihydropyridines.

The peptide omega-agatoxin IIIA (omega-Aga-IIIA) from venom of the funnel web spider Agelenopsis aperta blocks L-type Ca2+ channels in neurons and myocardial cells with high affinity. We report that omega-Aga-IIIA also blocks whole-cell Ca2+ channel currents in guinea pig atrial myocytes. Although other high affinity blockers of L-type Ca2+ channels are available (such as the 1,4-dihydropyridines), omega-Aga-IIIA is a valuable pharmacological tool; omega-Aga-IIIA is the only known ligand that blocks L-type Ca2+ channels with high affinity at all voltages (IC50 approximately 1 nM) and it causes little or no block of T-type Ca2+ channels, unlike the 1,4-dihydropyridines. We use omega-Aga-IIIA to selectively eliminate L-type Ca2+ currents and we show that felodipine blocks T-type Ca2+ currents. Consequently, the toxin is better than dihydropyridines for separating ionic currents through voltage-dependent Ca2+ channels and defining their physiological function.

Agatoxins

Direct cutaneous arterial supply to the tail in dogs.

Cutaneous arterial blood supply to the tail was evaluated in 12 dogs. Subtraction radiography of internal iliac artery and distal aorta angiography in 3 of these dogs was used to determine arterial blood supply to the tail from the median sacral and lateral caudal arteries. Dissection of the tail in 8 canine cadavers revealed bilateral subcutaneous location of lateral caudal arteries following tail amputation. An axial pattern flap based on the lateral caudal arteries contributed to the reconstruction of a large caudodorsal cutaneous defect in a dog. An axial pattern flap based on the lateral caudal arteries following tail amputation may be indicated to aid reconstruction of large caudodorsal cutaneous defects of the trunk in dogs.

Amputation, Surgical

Furcation anatomy of the first mandibular molar in dogs.

Tooth surface and interradicular area (furcation) measurements were taken of 20 first mandibular molar teeth obtained randomly from canine cadavers. The lingual furcation entrance had a mean width of 1.2 +/- 0.3 mm. The buccal furcation entrance had a mean width of 1.3 +/- 0.4 mm. There was no significant difference between mean furcation entrance measurements. The horizontal attachment area between the cementoenamel junction and the coronal roof of the lingual furcation was 1.1 +/- 0.4 mm. The horizontal attachment area between the cementoenamel junction and the coronal roof of the buccal furcation (0.5 +/- 0.3 mm) was significantly different from the lingual horizontal attachment area. Distal root length and mesial root length were 16.0 +/- 1.5 mm and 16.1 +/- 1.6 mm, respectively. The mean coefficient of variation for variables measured was 14.0%. Tooth size did not have a significant effect on furcation entrance measurement. All teeth had a concavity coronal to the furcation area, which extended apically for a mean distance of 65.6% of the distal root length and 83.8% of the mesial root length. Furcation anatomy of the first mandibular molar is complex and may be a contributing factor in periodontal disease involving the interradicular area.

Animals

Potential attachment area of the first mandibular molar in dogs.

Tooth root and root trunk surface area measurements were taken from 20 first mandibular molar (M1) teeth obtained randomly from canine cadaver specimens. The mean root surface area for all teeth was 497.1 +/- 116.2 mm2. The cumulative surface areas of the mesial (MR) and distal (DR) roots were 251.4 +/- 70.2 mm2 and 211.7 +/- 51.9 mm2, respectively. The root trunk surface area was 34.0 +/- 21.4 mm2. Surface area measurements for individual roots and the root trunk were significantly different. Cumulative individual root surface area (MR + DR) was 93.2% of total root surface area. The MR surface area contributed most to total root surface area (50.6%) and cumulative individual root surface area (54.3%). The mean distance from the beginning of the root trunk to the furcation was 2.1 mm. On the basis of the linear variation of the percentage of root surface area of the M1, 44.6% of the total root surface area was 3 to 7 mm apical to the most coronal aspect of the cementoenamel junction. The MR was heart-shaped, compared with the more cylindrical shape of the DR.

Animals

T-plate for middle carpal and carpometacarpal arthrodesis in a dog.

Partial arthrodesis was performed for carpal hyperextension injury in a dog. T-plate application for middle carpal and carpometacarpal arthrodesis was associated with low patient morbidity and allowed normal pet activity without clinical lameness. Radiography revealed bony healing of arthrodesed joints, reactive bone formation over the dorsal aspect of the plate, and periarticular osteophyte formation. A guarded prognosis is advised for degenerative joint disease that may lead to decreased range of motion of the antebrachiocarpal joint.

Animals

Nucleosome fractionation by mercury affinity chromatography. Contrasting distribution of transcriptionally active DNA sequences and acetylated histones in nucleosome fractions of wild-type yeast cells and cells expressing a histone H3 gene altered to encode a cysteine 110 residue.

A technique for the separation of transcriptionally active and inactive nucleosomes by mercury affinity chromatography has been applied to study the nucleosomal distribution of DNA sequences from the GAL1, ACT1, HIS4, MAT alpha, and HMRa genes of yeast. In mammalian cells, the method has been shown to separate active from inactive nucleosomes and to fractionate the active nucleosomes into two classes, one retained on the mercury column because of salt-labile associations with certain thiol-reactive non-histone proteins, and the other bound by covalent linkage of the cysteine 110 thiol groups of histone H3 molecules to the mercurated support. The first class of nucleosomes is elutable in 0.5 M NaCl; the second is displaced by 10 mM dithiothreitol (DTT) (Walker, J., Chen, T. A., Sterner, R., Berger, M., Winston, F., and Allfrey, V.G. (1990) J. Biol. Chem. 265, 5736-5746). We show that, in wild-type yeast cells, in which histone H3 lacks cysteinyl residues, very little DNA and a negligible complement of nucleosomes appear in the DTT-eluate, confirming the requirement for the H3-thiols in the mercury-binding reaction. Moreover, the DTT-eluted fraction is seriously deficient in the actively transcribed GAL1, ACT1, HIS4, and MAT alpha DNA sequences. Site-directed mutagenesis was employed to create an H3 gene containing a cysteine codon in place of the alanine codon at position 110 of the yeast H3 amino acid sequence. A strain was constructed containing the mutant histone H3 gene instead of the normal H3 gene. Subsequent fractionations of the mutant nucleosomes by mercury-affinity chromatography revealed a characteristic nucleosome peak in the DTT-eluted fraction. Its content of transcribed GAL1, ACT1, and HIS4 DNA sequences was 20- to 500-fold higher than that of the corresponding DTT-eluted fraction of wild-type yeast. Although this result is in accord with the finding that, in mammalian cells, the thiol groups of histone H3 become accessible when nucleosomes "unfold" during transcription, we find that nucleosomes containing the GAL1 DNA sequences of the yeast H3-mutant also bind to the mercury column when that gene is not being expressed. We conclude that many yeast nucleosomes are maintained in a "primed," potentially active state, possibly due to the very high constitutive levels of acetylation of the core histones. However, the nucleosomes of the HMRa gene, which is not expressed in a MAT alpha yeast strain, are virtually absent from the DTT-eluted nucleosome fractions of the H3-mutant cells, indicating that prolonged silencing of the gene is accompanied by compaction and loss of H3-thiol reactivity of its nucleosomes.

Acetylation

Intraoperative gamma detection probe with presurgical antibody imaging in colon cancer.

In this study, presurgical gamma camera imaging and an intraoperative gamma detection probe were used in 12 consecutive patients 6 to 22 days after infusion with indium 111-labeled anticarcinoembryonic antigen monoclonal antibody (111In-MoAb). In three of 11 patients who underwent laparotomy, clinical management was affected by the probe findings: localization of occult retroperitoneal disease, identification of an occult cecal lesion, and localization of residual disease at a site of local recurrence. Of all intra-abdominal lesions seen using any method, the probe identified 18 (86%) of 21, compared with 14 (67%) of 21 with the 111In-MoAb scan, 10 (48%) of 21 by computed tomographic scan, and 16 (76%) of 21 after surgical exploration. Uptake of 111In-MoAb in the portal (n = 3) and mediastinal (n = 3) lymph nodes was not associated with histologic findings of malignant neoplasms. For all pathologically confirmed extrahepatic and nonportal sites of cancer, the probe localized nine of nine, compared with five of nine by 111In-MoAb scan, two of nine by computed tomographic scan, and six of nine by surgical exploration. Important clinical uses of the intraoperative probe included occult lesion identification, localization of areas with 111In uptake shown with MoAb scanning, and verification of complete resection of areas with 111In-MoAb uptake.

Abdominal Neoplasms

Hepatitis E virus (HEV): molecular cloning and sequencing of the full-length viral genome.

We have recently described the cloning of a portion of the hepatitis E virus (HEV) and confirmed its etiologic association with enterically transmitted (waterborne, epidemic) non-A, non-B hepatitis. The virus consists of a single-stranded, positive-sense RNA genome of approximately 7.5 kb, with a polyadenylated 3' end. We now report on the cloning and nucleotide sequencing of an overlapping, contiguous set of cDNA clones representing the entire genome of the HEV Burma strain [HEV(B)]. The largest open reading frame extends approximately 5 kb from the 5' end and contains the RNA-directed RNA polymerase and nucleoside triphosphate binding motifs. The second major open reading frame (ORF2) begins 37 bp downstream of the first and extends approximately 2 kb to the termination codon present 65 bp from the 3' terminal stretch of poly(A) residues. ORF2 contains a consensus signal peptide sequence at its amino terminus and a capsid-like region with a high content of basic amino acids similar to that seen with other virus capsid proteins. A third open reading frame partially overlaps the first and second and encompasses only 369 bp. In addition to the 7.5-kb full-length genomic transcript, two subgenomic polyadenylated messages of approximately 3.7 and 2.0 kb were detected in infected liver using a probe from the 3' third of the genome. The genomic organization of the virus is consistent with the 5' end encoding nonstructural and the 3' end encoding the viral structural gene(s). The expression strategy of the virus involves the use of three different open reading frames and at least three different transcripts. HEV was previously determined to be a nonenveloped particle with a diameter of 27-34 nm. These findings on the genetic organization and expression strategy of HEV suggest that it is the prototype human pathogen for a new class of RNA virus or perhaps a separate genus within the Caliciviridae family.

Amino Acid Sequence

Histone structure and function.

The past year has seen major advances in our understanding of histone and nucleosome structure and function. Direct DNA mapping and thermodynamic experiments have finally provided conclusive evidence that the histones impose an altered helical pitch on the DNA as it is wrapped on the surface of the core histone octamer. Further, it is now clear that lysine acetylation in the amino-terminal domains of histones H3 and H4 can alter the topology of the DNA in chromatin and probably influence its higher-order folding. Genetic experiments reported in the past year have provided a wealth of new information on histone structure and function, including the identification of the peptide domain of histone H4 that is necessary for permanent gene repression, the confirmation that nucleosome structure is critical for centromere function, and evidence that histone acetylation plays a significant role in chromosome dynamics.

Amino Acid Sequence