Biomedical subjects
Publications and source records attributed to P Clark.
Structures consisting of connecting rings surrounding a fibrillar core were observed within nucleoli of developing normal and axotomized hamster facial motoneurons. A few appeared in the nucleoplasm, attached to coiled bodies. Their peculiar structure and temporal association with neuronal maturation may reflect a transient state of ribosomal RNA transcription.
The study utilizes an ex vivo perfusion model to evaluate the effects of warm perfusion (25 degrees C) with two K+-rich vehicle solutions (RPS-2 and solution A) on whole rabbit kidneys. The suitability of the solutions as vehicles for introducing cryoprotectant concentrations (2.8 and 3.5 M) of dimethyl sulfoxide (Me2SO) and the effects of the addition of albumin to RPS-2 are also tested. Albumin (5 g/dl) does not appreciably improve the renal perfusion dynamics of RPS-2. Results indicate that both RPS-2 and solution A serve as effective vehicles for the introduction of 2.8 M Me2SO, and the continued investigation of the RPS-2/Me2SO protocol is advocated.
The association between alpha 1-antitrypsin (alpha 1-AT) deficiency and a number of immune mediated diseases including rheumatoid arthritis, anterior uveitis, systemic lupus erythematosus, and asthma suggests that alpha 1-AT may be important not only as an anti-inflammatory protein but also as an immune regulator. That the relationship between decreased amounts of this inhibitor and these diseases is causal is suggested by both some of its physical properties and evidence indicating it is able to modulate immune function. alpha 1-Antitrypsin has a high plasma concentration, very broad range of inhibitory activity and is an acute phase reactant. Among other things, it is able to modulate lymphocyte proliferation and cytotoxicity, and monocyte and neutrophil function. Additionally, some of these changes are demonstrable in vivo in patients with severe alpha 1-antitrypsin deficiency. This paper reviews the important physicochemical characteristics of this protein, the association of its presence in decreased amounts with immune disorders, and finally the important mechanism that may underlie this disease association.
Eighty-five adults with horizontal concomitant strabismus were treated with an injection of a low dose of botulinum toxin A (BTXA) into the lateral or medial rectus muscle. The ocular deviation was reduced by an average of 60% independently of its size and whether or not surgery had previously been performed. The change was temporary, however, except in those cases with binocular functions, when fusion was re-established. Repeated low dose injections can maintain the improvement, but at higher doses, although larger reductions are produced, temporary local side effects--ptosis and vertical strabismus--are common. The technique is simple, well tolerated, and has no systemic side effects.
alpha 1 antitrypsin is an important immunoregulatory protein, the serum level of which is genetically determined. Deficient phenotypes of this ubiquitous protease inhibitor are associated with a variety of inflammatory diseases including anterior uveitis. In order to investigate the role of this protease inhibitor in the pathogenesis of retinal vasculitis (RV) 25 patients were investigated. Diseases associated with RV included Behcet's syndrome (8), SLE (2), and sarcoidosis (1). Deficient phenotypes of alpha 1 antitrypsin were not associated with RV. However, the serum alpha 1 antitrypsin level was significantly increased in patients with active RV and paralleled disease activity in patients studied prospectively.
Fifty-three persons wearing soft-lined mandibular dentures and heat-cured acrylic-resin maxillary dentures were studied, using imprint cultures, to determine the isolation frequency and density of colonization of denture and mucosal surfaces by yeasts. Yeasts were isolated from 35 (66%) of the persons studied. Nine species of Candida and one each of Trichosporon and Saccharomyces were identified. Candida albicans, occurring either alone or together with another strain, was identified in 66% of the isolates and was associated with a higher mean density/cm2 than that of other strains. An association between the method of denture cleaning, denture hygiene, and smoking habits and the isolation of yeasts was demonstrated, but a similar association could not be demonstrated with the sex of the person, denture-wearing habits, type and condition of the soft lining, or the clinical appearance of the mandibular denture-bearing mucosa. Although yeasts are more likely to colonize soft-lining materials than the fitting surface of conventional lower dentures, their presence did not significantly affect the soft-lining material. Further, the increased isolation of yeasts on the fitting surface of the soft-lined mandibular denture was not associated with an increased incidence of inflammatory changes in the mandibular denture-bearing mucosa.
The capillary is the principal barrier at high Vo2. Mathematical modelling indicates that at high flow and Vo2 the time required for release of O2 is greater than red cell transit time in some capillaries. This convective shunting appears to be particularly important in the myocardium. The Mb acts to buffer Po2 below 5 Torr during muscle contraction. This greatly increases the transcapillary O2 gradient and promotes O2 delivery. During voluntary movements, Mb should act as a major O2 source in parallel with capillaries. The Kroghian model of the capillary as a "low-resistance" point source of O2 supplying a spatially uniform sink appears to be the reverse of the actual geometry of O2 supply to working red muscle.
A renal cortical slice model was used to assess the effects on viability of three vehicle solutions-Krebs-Henseleit (K-H), solution A, and RPS-2--at 25 degrees C. After 120 min incubation no differences in [K+]/[Na+] ratios were found. Tracer techniques were used to study the osmotic effects and permeation kinetics at 25 degrees C of three cryoprotectants (dimethyl sulfoxide (Me2SO), ethylene glycol, and glycerol) and the effect of the vehicle solution (K-H or RPS-2) on Me2SO kinetics. It was found that Me2SO was most permeable and ethylene glycol least, and that ethylene glycol had unusual effects which suggest that it may not act as a simple solute. Differences were found when Me2SO was introduced in K-H and RPS-2 that are believed to be related to the binding properties of Me2SO to cell constituents.
The [K+]/[Na+] ratio of rabbit renal cortical slices was used to examine, at 25 degrees C, the effects on viability of three cryoprotectant agents (CPA) (dimethyl sulfoxide (Me2SO), ethylene glycol, and glycerol) in combination with three vehicle solutions (Krebs-Henseleit (K-H), solution A, and RPS-2). Viability assessment by [K+]/[Na+] for all test solutions was made after incubating the slices in modified Cross-Taggart solution (C-T). With K-H and solution A, all concentrations of ethylene glycol and glycerol resulted in lowered ratios, whereas with Me2SO, concentrations greater than 1.4 M are required to reduce [K+]/[Na+]. With RPS-2 no decrease in the ratios was found until concentrations greater than 2.8 M were reached for all three CPAs. Binding of Me2SO to albumin, studied using [14C]Me2SO, was inhibited by RPS-2 when compared to K-H. Introduction and removal of Me2SO at 10 degrees C allowed an improvement in viability, at higher Me2SO concentrations, as compared to 25 degrees C.
Addition of copper to yeast cells leads to the induction of a low molecular weight, cysteine-rich protein that binds copper. This protein, termed copper chelatin or thionein, is related to the metallothionein family of proteins that are induced in response to cadmium and zinc in vertebrate cells. We have determined the structure of the yeast copper-binding protein by DNA sequence analysis of the gene. Although the 6573-dalton yeast protein is substantially divergent from vertebrate metallothioneins, the arrangement of 12 cysteine residues, which is a hallmark of metal-binding proteins, is partially conserved. We analyzed the regulatory DNA sequence of the gene by fusing it with the Escherichia coli galactokinase gene and assaying the levels of enzyme activity in yeast in response to copper. The transcriptional activation has a specific requirement for copper. Zinc, cadmium, and gold were unable to regulate the galactokinase activity. The yeast copper metallothionein regulatory sequences represent a previously unreported class of yeast promoter that is regulated by copper.
Sendai and Newcastle disease viruses were tested for their induction potential in the production of human lymphoblastoid interferon [HuIFN-alpha(Ly)] from Namalva cell cultures. Tests were performed at multiple induction levels, for two induction periods, and on primed and nonprimed cell cultures. Sendai virus proved statistically more effective overall; priming and induction period had no significant effect.
In a 3-year period of prospective study, 250 pediatric patients with multiple trauma (injury to at least two body areas) had injuries scored by a modification of the Injury Severity Scale (MISS). This scale uses the categories and rankings of the Abbreviated Injury Scale-1980 (AIS-80) except for neurologic injuries. Neurologic injuries are scored by using a combination of the Glasgow Coma Scale (GCS) and other neurologic findings (presence of surgical mass lesion, pupillary light response, and oculocephalic reflexes). The MISS is calculated as the sum of the squares of the three most severely injured body areas. The mean MISS score was 27.8, with 38% of MISS scores greater than or equal to 25 and 62% less than 25. Among those with MISS scores greater than or equal to 25 there was a 40% mortality and 30% disability, while there were no mortalities and 1% disability for those with MISS scores less than 25 (p less than 0.001). Overall mortality was 15%, with 10% disability. Mean MISS scores for death and disability were 33.4 and 30.2, respectively. Neurologic injuries were present in 173 patients (69%); 128 patients had severe head injuries (coma greater than 6 hours duration); 80% of all deaths were due to neurologic injury and all but two deaths had some degree of head injury; the remaining 20% of deaths were due to chest and abdominal injuries. Patients with MISS grade 5 injury (critical, survival uncertain) had 73% mortality, while those with grades 4 and 3 injury had 8% and 2% mortality, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
The minimum significant (p = 0.05 level) detectable change noted on measuring anterior chamber depth by a photographic method was found to be 7% either way from the mean. The minimum significant change for a peripheral chamber depth 5 mm from the optic axis was found to be 25% either way.
One example of each of two approaches to the isolation of molecular hybridization probes and their use for the comparative investigation of gene expression and its control during differentiation of normal and leukaemic leukocytes is described. RNA preparations from the peripheral blood leukocytes of human leukaemias of various types were assayed for the relative abundance of the mRNA homologous with a cellular oncogene, c-myc. All types of leukaemia except chronic lymphatic leukaemia (CLL) showed varying levels of myc-related RNA; the highest concentrations occurred in cell populations in which blast cells predominated. In contrast, a recombinant plasmid (pCG14), isolated from a cDNA recombinant plasmid library that represented polyadenylated RNAs from the peripheral blood leukocytes of a chronic granulocytic leukaemia (CGL), hybridized with an mRNA whose occurrence is diagnostic of CGL leukocytes. This mRNA was also found in normal bone marrow cells; in both bone marrow and in CGL leukocytes, pCG14-homologous RNA occurs only in cells around the myelocyte stage in differentiation. It is suggested that these probes, and others for mRNAs whose occurrence is specific to a particular cell lineage and/or stage in differentiation, detect a new series of potential diagnostic markers. These might usefully supplement existing ones to provide a more detailed, objective subclassification of the leukaemias which could have important implications for diagnosis and therapy.
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A grid system is described which may be superimposed upon stereoscopic pairs of optic disc photographs. This grid system allowed reproducible inter- and intraobserver measurements of the cup/disc (C/D) ratio. The surface contour of the optic disc was not clear-cut in approximately 10% of the population studied, which led to a reduction in reproducibility of the measurement made within the group as a whole. As a result it was found that a large increase in the C/D ratio would have to occur for such change to be of statistical significance. Even with an optic grid as a reference system the serial measurements of the C/D ratio are unlikely to be of value in the management of patients with chronic glaucoma.
Associations have been found between self-reported cold symptoms and Pi type in 84 pairs of identical twins. The risk of cold symptoms relative to MM phenotypes was 1.2 times greater in MS and 2.5 times greater in MZ individuals. Up to 9% of variance in cold symptoms could be attributed to Pi type, representing at least 20% of the total genetical variance.