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Biomedical subjects

R A Pollock

Publications and source records attributed to R A Pollock.

At least 37 records · Page 2Linked to original sources
PubMed1994

The psychopharmacology of social phobia and comorbid disorders.

The pharmacotherapy of social phobia includes agents from different classes with different mechanisms of action and has recently become the focus of more attention in the research community. The authors highlight drug treatments with reported efficacy, including: (1) certain antidepressants: monoamine oxidase inhibitors, selective serotonin reuptake inhibitors, and other antidepressants not yet available in the United States such as reversible inhibitors of MAO-A; (2) high-potency benzodiazepines; and (3) beta-adrenergic blocking drugs (mainly for performance anxiety). The frequent co-occurrence of social phobia with other psychiatric disorders often complicates patient management, treatment, and outcome. Rates of comorbidity, principles of pharmacotherapy for the comorbid condition, and the potential advantages and disadvantages of the aforementioned agents in social phobia patients suffering comorbid disorders are discussed.

Adrenergic beta-Antagonists↗
PubMed1994

The etiology of social phobia.

Human beings are by nature social animals, but for some, social scrutiny is a source of extreme anguish. Those with social phobia, for example, suffer excessive and often disabling concern about potential and real social-evaluative threat. As new and effective therapies for this condition are pursued, there is a simultaneous movement to extend the understanding of this disorder's etiology. In psychiatry, as in the rest of medicine, this development of new treatments often occurs in parallel with increasing sophistication about causes of illness. Advances in one area typically inform and predictably lead to advances in the other. Social phobia is recognized as a relatively common and significantly impairing anxiety disorder. As with other psychiatric disorders, emerging models of the etiology of social phobia are derived from converging evidence of interacting biological and environmental contributions. Current theories regarding the evolution of social phobia will be addressed, including biological preparedness to fear scrutiny by others, genetically transmitted predisposition to fear acquisition, nongenetic familial and environmental factors, as well as other possible causes and antecedents. Additionally, we describe recent work on behavioral inhibition in infancy as an identifiable early marker of proneness to the development of anxiety disorders, including social phobia.

Adolescent↗
PubMed1993

PDGF and its receptors in the developing rodent retina and optic nerve.

We have used in situ hybridization to visualize cells in the developing rat retina and optic nerve that express mRNAs encoding the A and B chains of platelet-derived growth factor (PDGF-A and PDGF-B), and the alpha and beta subunits of the PDGF receptor (PDGF-alpha R and PDGF-beta R). We have also visualized PDGF-A protein in these tissues by immunohistochemistry. In the retina, PDGF-A mRNA is present in pigment epithelial cells, ganglion neurons and a subset of amacrine neurons. PDGF-A transcripts accumulate in ganglion neurons during target innervation and in amacrine neurons around the time of eye opening, suggesting that PDGF-A expression in these cells may be regulated by target-derived signals or by electrical activity. In the mouse retina, PDGF-A immunoreactivity is present in the cell bodies, dendrites and proximal axons of ganglion neurons, and throughout the inner nuclear layer. PDGF-alpha R mRNA is expressed in the retina by astrocytes in the optic fibre layer and by a subset of cells in the inner nuclear layer that might be Müller glia or bipolar neurons. Taken together, our data suggest short-range paracrine interactions between PDGF-A and PDGF-alpha R, the ligand and its receptor being expressed in neighbouring layers of cells in the retina. In the optic nerve, PDGF-A immunoreactivity is present in astrocytes but apparently not in the retinal ganglion cell axons. PDGF-alpha R+ cells in the optic nerve first appear near the optic chiasm and subsequently spread to the retinal end of the nerve; these PDGF-alpha R+ cells are probably oligodendrocyte precursors (Pringle et al., 1992). RNA transcripts encoding PDGF-B and PDGF-beta R are expressed by cells of the hyaloid and mature vascular systems in the eye and optic nerve.

Animals↗
PubMed1992

Altering the boundaries of Hox3.1 expression: evidence for antipodal gene regulation.

To investigate the function of region-specific patterns of mouse homeobox gene expression during embryogenesis, we programmed a minimal change in the distribution of Hox3.1 transcripts along the anteroposterior body axis in transgenic mice. Regulatory sequences from Hox1.4, a gene normally expressed more anteriorly than Hox3.1, were chosen to direct expression of a Hox3.1 transgene. Offspring of independent transgenic lines expressed the transgene more anteriorly than the Hox3.1 gene. Rather than predicted posterior transformations, we observed anterior transformations of vertebrae in newborn mice. Transgenic mice also developed profound gastrointestinal tissue malformations, which may provide a molecular explanation for human developmental disorders often involving these same two regions. Paradoxically, vertebral transformations in the transgenic mice were strikingly similar to those reported in mice homozygous for a null mutation of the Hox3.1 gene. This observation suggests that Hox genes may be regulated antipodally, with over- or underexpression resulting in similar phenotypes.

Animals↗
PubMed1992

The alternative-splice isoforms of the PDGF A-chain differ in their ability to associate with the extracellular matrix and to bind heparin in vitro.

Platelet-derived growth factor (PDGF) consists of disulfide-linked homo- or heterodimers of A and B chains. mRNA encoding the A chain (PDGF-A) occurs in two versions that differ by the presence or absence of a single short exon. These alternatively-spliced mRNAs encode polypeptides that differ in length by fifteen amino acids. The longer isoform (PDGF-AL) possesses a highly basic carboxy-terminal extension that is responsible for retaining PDGF-AL homodomers at the cell surface after secretion, while homodimers of the shorter isoform (PDGF-AS) are released into the extracellular medium. We have investigated the mechanism by which PDGF-AL remains in association with the cells that produce it. We expressed epitope-tagged versions of PDGF-AL and PDGF-AS in Cos cells and compared their intra- and extracellular distributions by immunofluorescence microscopy. PDGF-AL, but not PDGF-AS, was detected on and around cells in a diffuse pattern suggesting associated with the extracellular matrix (ECM). Metabolically radiolabelled PDGF-AL, but not PDGF-AS, could be eluted from ECM preparations by washing in high salt. Moreover, PDGF-AL bound reversibly to heparin-Sepharose in vitro at physiological salt concentrations, eluting at a salt concentration around 0.5 M. PDGF-AS did not bind to heparin under the same conditions. Thus, PDGF dimers that contain PDGF-AL may remain immobilized near the cells that secrete them by virtue of binding to heparin-like constituents of the ECM.

3T3 Cells↗
PubMed1992

Nasal trauma. Pathomechanics and surgical management of acute injuries.

This article delineates the structural features of the nose and discusses the major patterns of nasal injury as seen in the cadaveric laboratory and in the setting of two large metropolitan surgical centers. Diagnostic methods are reviewed, including a test of structural integrity by digital compression. Methods of reduction, internal fixation, and techniques of grafting that include the use of overlay and underlay cantilevers complete the author's approach to nasal injury.

Biomechanical Phenomena↗
PubMed1991

Mitochondrial protein import.

A dynamic picture of the mitochondrial protein import pathway is emerging, with conformational alteration a critical feature both preceding and following membrane translocation. The mediators of these steps of conformational alteration, as well as steps of recognition, translocation, and proteolytic cleavage, appear to be proteins. Using powerful tools of genetics and biochemistry, in years to come it should be possible to determine the precise molecular function of these proteins in mediating these novel reactions.

Animals↗
PubMed1991

Reduction mammoplasty with free-nipple transplantation: indications and technical refinements.

Multiple techniques for breast reduction have been proposed. For carefully selected women with macromastia, the technique of choice may be amputation mammoplasty with free nipple-areolar grafting. These select groups include the following: the poor-risk elderly, women with systemic disease that could affect the vascularity of the skin flaps or impair wound healing, women with previous operative procedures in the breast affecting skin flap or pedicle vascularity, and women with indications for removal of tissue in the region of the inferior pedicle. Our experience demonstrates that in these high-risk women, amputation mammoplasty with certain technical refinements provides an aesthetic safe result without significant perioperative surgical or medical complications. A clinical series is presented with an average follow-up of 2.75 years.

Breast↗
PubMed1989

Combined injuries of the cranium and face.

The neurosurgeon and plastic surgeon are increasingly called upon to manage the care of patients with combined injuries of the cranium and face. The authors briefly review the pathogenesis and classification of craniofacial fractures and outline historical approaches to them. Current principles of management are then discussed. Experience with 167 patients is presented with emphasis on surgical technique, the sequence of repair and early primary reconstruction. The controversial issue of fontal sinus fracture repair is addressed. The authors favour preservation of the frontal sinus cavity, where possible, and do not obliterate the nasofrontal duct. With injuries to the floor of the sinus, the base of the sinus and frontonasal duct are sealed with bone graft and a vascularised soft tissue flap and the sinus is cranialised. Immediate bone grafts, using split skull or rib, are used to reconstruct areas of bony destruction or loss. Ninety-eight patients required 402 grafts. Immediate bone grafting resulted in few complications and low incidence of secondary deformities needing correction.

Facial Bones↗
PubMed1988

The processing peptidase of yeast mitochondria: the two co-operating components MPP and PEP are structurally related.

Two proteins co-operate in the proteolytic cleavage of mitochondrial precursor proteins: the mitochondrial processing peptidase (MPP) and the processing enhancing protein (PEP). In order to understand the structure and function of this novel peptidase, we have isolated mutants of Saccharomyces cerevisiae which were temperature sensitive in the processing of mitochondrial precursor proteins. Here we report on the mif2 mutation which is deficient in MPP. Mitochondria from the mif2 mutant were able to import precursor proteins, but not to cleave the presequences. The MPP gene was isolated. MPP is a hydrophilic protein consisting of 482 amino acids. Notably, MPP exhibits remarkable sequence similarity to PEP. We speculate that PEP and MPP have a common origin and have evolved into two components with different but mutually complementing functions in processing of precursor proteins.

Amino Acid Sequence↗
PubMed1988

Identification of a putative structural gene for cathepsin D in Caenorhabditis elegans.

Mutants of Caenorhabditis elegans having about 10% of wild-type activity of the aspartyl protease cathepsin D have been isolated by screening. Mutant homozygotes have normal growth rates and no obvious morphological or developmental abnormalities. The mutant gene (cad-1) has been mapped to the right extremity of linkage group II. Heterozygous animals (cad-1/+) show intermediate enzyme levels and animals heterozygous for chromosomal deficiencies of the right extremity of linkage group II have 50% of wild-type activity. Cathepsin D purified from a mutant strain has a lower activity per unit mass of pure enzyme. These data suggest that cad-1 is a structural gene for cathepsin D.

Animals↗
PubMed1988

AO/ASIF plate for mandibular reconstruction in tumor surgery: results in 20 cases.

Between May, 1983, and February, 1987, the authors performed mandibular reconstruction using an AO/ASIF plate in 20 patients. Apart from accurate modelling of the resected segment using a template, the key features of the technique include firm fixation and wrapping the plate with pectoralis major muscle. In 19 cases the plate was inserted at the same operation as the resection of a malignant neoplasm. In 10 cases the anterior mandibular osteotomy was placed on the far side of the midline, while in five the mandible was disarticulated through the temporomandibular joint. Eleven patients are alive (average survival 22 months) and nine have died (average survival 10 months). Two AO/ASIF plates have required removal because of exposure, while in three patients limited plate exposure was corrected with a minor surgical procedure. Seven patients had soft tissue complications that were managed conservatively. Nine of the patients had been irradiated previously. Five patients were fitted with dentures successfully. The authors believe that this technique provides a safe, rapid, functional and esthetically satisfactory method of mandibular reconstruction in the patient undergoing surgery for malignant disease.

Adult↗
PubMed1987

Import and processing of human ornithine transcarbamoylase precursor by mitochondria from Saccharomyces cerevisiae.

Expression of the subunit precursor of the human mitochondrial matrix enzyme ornithine transcarbamoylase (OTCase; EC 2.1.3.3) was programmed in Saccharomyces cerevisiae from a 2-micron plasmid by using an inducible galactose operon promoter. In the presence of the inducing sugar (galactose), two polypeptides were specifically precipitable with anti-OTCase antiserum: the human OTCase precursor (40 kDa); and the mature OTCase subunit (36 kDa). When yeast cells containing these species were lysed and fractionated, the OTCase precursor was found to be associated with mitochondrial membranes, while the mature subunit was found partly with mitochondrial membranes and partly in the soluble mitochondrial matrix-containing fraction. When OTCase enzymatic activity was assayed in fractions similarly derived from an S. cerevisiae strain devoid of yeast OTCase activity (an arg3 mutant) but expressing human OTCase, activity was detected specifically in the mitochondrial matrix fraction. A mutant human OTCase precursor containing an artificial mutation in the NH2-terminal leader peptide (arginine-23 to glycine) was similarly examined. As was previously observed with mammalian mitochondria, this precursor failed both to reach the matrix compartment and to be proteolytically processed; it also failed to exhibit OTCase enzymatic activity. Presence of OTCase enzymatic activity in an arg3 strain expressing wild-type precursor was utilized to obtain selective growth in a medium devoid of arginine but supplemented with the OTCase substrate ornithine. We conclude that, during evolution, the pathway of mitochondrial import utilized by the human OTCase precursor is conserved between yeast and humans, and that, by using selective growth conditions, it may be possible to examine genetically this pathway in S. cerevisiae.

Enzyme Precursors↗
PubMed1987

The ornithine transcarbamylase leader peptide directs mitochondrial import through both its midportion structure and net positive charge.

The cytoplasmically synthesized precursor of the mitochondrial matrix enzyme, ornithine transcarbamylase (OTC), is targeted to mitochondria by its NH2-terminal leader peptide. We previously established through mutational analysis that the midportion of the OTC leader peptide is functionally required. In this article, we report that study of additional OTC precursors, altered in either a site-directed or random manner, reveals that (a) the midportion, but not the NH2-terminal half, is sufficient by itself to direct import, (b) the functional structure in the midportion is unlikely to be an amphiphilic alpha-helix, (c) the four arginines in the leader peptide contribute collectively to import function by conferring net positive charge, and (d) surprisingly, proteolytic processing of the leader peptide does not require the presence of a specific primary structure at the site of cleavage, in order to produce the mature OTC subunit.

Amino Acid Sequence↗
PubMed1987

The gluteus maximus musculocutaneous island flap: refinements in design and application.

The gluteus maximus island musculocutaneous flap has been described using a variety of designs. We employ an island whose long axis is directed toward the pressure sore, minimizing tension in wound closure. Skin overlying the greater trochanter is avoided. Previously undermined skin can be included in the flap. Fifty patients with ischial or sacral pressure sores have been managed by this technique. Superficial dehiscence occurred in 13 percent of patients, and deep dehiscence occurred in 10 percent. The dehiscence closed spontaneously in all but one patient. Forty-nine of the 50 patients experienced complete wound healing at the pressure sore site. The patients have been observed for an average of 20 months (range 3 to 38 months), with one recurrent pressure sore seen at 28 months postoperatively. The gluteus maximus musculocutaneous island flap has proven to be both reliable in healing and durable over the observed interval.

Buttocks↗
PubMed1986

Targeting of pre-ornithine transcarbamylase to mitochondria: definition of critical regions and residues in the leader peptide.

The cytoplasmically synthesized precursor of the mitochondrial matrix enzyme, ornithine transcarbamylase (OTC), is directed to mitochondria by its amino-terminal leader peptide. To define the critical residues and/or regions in the OTC leader peptide, we have synthesized OTC precursors with alterations in the leader portion. Analysis of deletions reveals that the middle portion of the 32 residue leader peptide is absolutely required for both mitochondrial uptake and proteolytic processing, whereas NH2-terminal and penultimate COOH-terminal portions are not. Analysis of precursors with single substitutions revealed complete loss of function when arginine 23 was substituted with glycine. Additional substitutions suggested that the critical role of this arginine residue may be mediated by participation in a local secondary structure, very likely an alpha-helix, which is proposed to be an essential element in the midportion of the leader peptide.

Arginine↗
PubMed1985

Congenital hemifacial hyperplasia: an embryologic hypothesis and case report.

Congenital hyperplasia is a developmental disorder characterized by marked unilateral asymmetry. The structural disproportions from one side to the other far exceed variations commonly seen in the normal population. Classically, as first described in 1836, the overgrowth of tissue is restricted to one-half of the body, including the extremities. In other cases the hyperplastic enlargement involves segmental areas of the body, such as the hemifacial skeleton and an extremity. A case report is presented, and the clinical characteristics of 192 cases of congenital hyperplasia in the literature are briefly reviewed. Use of the word hyperplasia to describe the condition (rather than hypertrophy) is encouraged. The authors propose a new embryologic hypothesis: asymmetrical development of the neural fold and hyperplasia of the neural crest cells are said to form the basis for the disorder. The rewards, risks, and limitations of reconstructive surgery over a 10-year period are discussed.

Child, Preschool↗