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Biomedical subjects

J Wolfe

Publications and source records attributed to J Wolfe.

At least 181 records · Page 10Linked to original sources
PubMed1986

Mechanical responses of developing Fisher rat heart. Effects of steroid hormone.

Age-dependent changes in the mechanical responses of developing Fisher rat heart during the first three postnatal weeks were studied in relation to the hypothesis that the abnormality observed in the mechanical responses of the rat heart might be calcium related. Therefore the effect of frequency of stimulation as well as the response to calcium, epinephrine and ouabain on hearts of untreated and cortisol-treated rats was compared. The positive force-frequency response observed in fetal rat heart reverted to a highly negative response by the 12th to 14th postnatal day. The biphasic mechanical responses directly paralleled reported changes in circulating glucocorticoid levels in developing rat. The force-frequency response was maximally negative when the circulating levels of glucocorticoids were lowest. The reversion of the negative force-frequency responses coincided with a gradual increase reported in the circulating levels of glucocorticoids. The negative force-frequency response was absent in the cortisol-treated developing rat heart and a definite positive pattern was observed as the rats developed. A high sensitivity to free calcium concentration, seen in control fetal and and newborn hearts, diminished after the second postnatal week. By the third postnatal week, the sensitivity to high extracellular calcium concentrations was significantly reduced. The sensitivity to calcium persisted in the cortisol-treated hearts during the 3 postnatal weeks. Cortisol-treated hearts were more responsive to epinephrine than controls. The abbreviation of time to peak tension, a hallmark of the catecholamine effect, was observed at a younger age in the cortisol-treated hearts. Cortisol-treated hearts were more responsive to the inotropic effects of ouabain than controls. The possible involvement of glucocorticoids in the control of calcium handling elements of the myocardium is discussed.

Animals↗
PubMed1985

Isolation and characterization of an alphoid centromeric repeat family from the human Y chromosome.

A collection of human Y-derived cosmid clones was screened with a plasmid insert containing a member of the human X chromosome alphoid repeat family, DXZ1. Two positive cosmids were isolated and the repeats they contained were investigated by Southern blotting, in situ hybridization and sequence analysis. On hybridization to human genomic DNAs, the expected cross-hybridization characteristic of all alphoid sequences was seen and, in addition, a 5500 base EcoRI fragment was found to be characteristic of a Y-specific alphoid repeat. Dosage experiments demonstrated that there are about 100 copies of this 5500 base EcoRI alphoid fragment on the Y chromosome. Studies utilizing DNA from human-mouse hybrids containing only portions of the Y chromosome and in situ hybridizations to chromosome spreads demonstrated the Y centromeric localization of the 5500 base repeat. Cross-hybridization to autosomes 13, 14 and 15 was also seen; however, these chromosomes lacked detectable copies of the 5500 base EcoRI repeat sequence arrangement. Sequence analysis of portions of the Y repeat and portions of the DXZ1 repeat demonstrated about 70% homology to each other and of each to the human consensus alphoid sequence. The 5500 base EcoRI fragment was not seen in gorilla, orangutan or chimpanzee male DNA.

Animals↗
PubMed1985

Sorbitol/fructose metabolism in the lens.

The function of the sorbitol pathway, both as a secondary energy source and as an osmotic counterbalancing force, was examined. Rat lenses were incubated in media containing fructose as the primary exogenous energy source, and 31P nuclear magnetic resonance (NMR) spectra were accumulated. Fructose was found to be a sub-optimal but usable substrate for glycolysis. The utilization of fructose was further confirmed by a 14C fructose tracer study, using high-pressure liquid chromatography. Thus the intralenticular pool of sorbitol + fructose could serve as a secondary energy source during severe hypoglycemia in the diabetic lens. However, fructose is not a physiologically significant alternative to glucose. 13C NMR spectroscopy was employed to determine the kinetics of sorbitol/fructose accumulation in lenses incubated in 35.5 mM 13C1-glucose, and the sorbitol/fructose consumption after the preincubated lenses were transferred to media containing no glucose. Based on these kinetic studies, we concluded that the sorbitol pathway cannot generate sorbitol/fructose fast enough to offset increased osmotic pressure from high glucose levels in the aqueous humor of the diabetic eye. The contribution of osmotic equivalents from sorbitol + fructose, however, cannot be ignored.

Adenosine Triphosphate↗
PubMed1985

Validity and reproducibility of the Cooperative Cataract Research Group (CCRG) cataract classification system.

The validity and reproducibility with which six classifiers [one experienced (L.T.C.), and five novices (W.G., F.G., W.W., J.W. and O.W.)] used the CCRG cataract classification system was assessed. The validity of index classifications was assessed by computing sensitivities and pairwise interclass correlations between experienced and novice classifiers using the former's classification as the standard. The number of unordered combinations of terms in the CCRG's classification was reduced by combining cortical terms according to the CCRG's accepted system of staged simplification. The number of combinations of terms at each stage is as follows: Stage I (greater than 1000); II (127); III (63); IV (15); V (7); VI and VII (3) and VIII (2). Excellent agreement was obtained between the experienced and novice classifiers for Stages VII and VIII of the classification, good agreement for Stages V and VI and poor agreement for Stages IV, III and II (sensitivities of 97, 96, 72, 59, 40, 24 and 20% respectively). Good agreement was also achieved for the classifications of single lenticular regions, except for subcapsular regions. The intra- and interobserver reproducibility was assessed by computing the Kappa statistic to (1) compare classifications between novice observers and (2) compare repeat classifications made by the same observer by viewing the same cataract once on each of three different days. The novice classifiers had excellent intraobserver reproducibility for Stages VII and VIII (Kappas of 0.87 and 0.97 respectively), good reproducibility for Stages IV, V and VI (Kappas of 0.53, 0.62 and 0.62, respectively) and marginal reproducibility for stages II and III (Kappas of 0.39 and 0.40, respectively). The intraobserver reproducibility of the experienced classifier was superior to the others for virtually all characteristics with excellent reproducibility for Stages IV, V, VI, VII and VIII with Kappas of 0.79, 0.90, 1.0, 1.0 and 1.0, respectively and good reproducibility for Stages II and III (Kappas of 0.55 and 0.64, respectively). These results indicate that the simplified CCRG cataract classification system (Stages IV-VIII) passes the minimum standards for reproducibility. The performance of the experienced classifier far exceeds the minimum standards and indicates the feasibility of improving classifier performance with training and practice.

Cataract↗
PubMed1985

Memory disorders associated with Huntington's disease: verbal recall, verbal recognition and procedural memory.

Two experiments were conducted to evaluate the hypothesis that the memory disorders of Huntington's Disease (HD) patients are characterized by deficiencies in both retrieval mechanisms and the acquisition of procedural (skill-based) information. In the first study, verbal recall and recognition tests were administered to HD patients, amnesics and normal control (NC) subjects. Although the two patient groups were impaired relative to NC subjects on both recall and recognition of word lists, the performance of the HD patients was superior to that of the amnesics on the recognition test. In the second experiment early HD (EHD), advanced HD (AHD), amnesic and NC subjects were compared in the acquisition of the 'Tower of Hanoi' puzzle. Both the NC subjects and EHD patients acquired the solution of this puzzle after repeated trials, whereas the AHD and amnesic patients evidenced little improvement. However, on a recognition test assessing memory for facts about the puzzle, both the EHD and AHD patients were superior to the amnesic subjects. These results are consistent with the retrieval hypothesis but are equivocal with regard to the HD patients' proposed deficit in skill learning. Since the 'Tower' puzzle may rely heavily on both problem solving and skill learning capabilities, it may be of limited value in searching for double dissociations between patient groups and the acquisition of skill-based and data-based knowledge.

Adult↗
PubMed1985

The human Y chromosome.

Despite its central role in sex determination, genetic analysis of the Y chromosome has been slow. This poor progress has been due to the paucity of available genetic markers. Whereas the X chromosome is known to include at least 100 functional genetic loci, only three or four loci have been ascribed to the Y chromosome and even the existence of several of these loci is controversial. Other factors limiting genetic analysis are the small size of the Y chromosome, which makes cytogenetic definition difficult, and the absence of extensive recombination. Based on cytogenetic observation and speculation, a working model of the Y chromosome has been proposed. In this classical model the Y chromosome is defined into subregions; an X-Y homologous meiotic pairing region encompassing most of the Y chromosome short arm and, perhaps, including a pseudoautosomal region of sex chromosome exchange; a pericentric region containing the sex determining gene or genes; and a long arm heterochromatic genetically inert region. The classical model has been supported by studies on the MIC2 loci, which encode a cell surface antigen defined by the monoclonal antibody 12E7. The X linked locus MIC2X, which escapes X inactivation, maps to the tip of the X chromosome short arm and the homologous locus MIC2Y maps to the Y chromosome short arm; in both cases, these loci are within the proposed meiotic pairing region. MIC2Y is the first biochemically defined, expressed locus to be found on the human Y chromosome. The proposed simplicity of the classical model has been challenged by recent molecular analysis of the Y chromosome. Using cloned probes, several groups have shown that a major part of the Y chromosome short arm is unlikely to be homologous to the X chromosome short arm. A substantial block of sequences of the short arm are homologous to sequences of the X chromosome long arm but well outside the pairing region. In addition, the short arm contains sequences shared with the Y chromosome long arm and sequences shared with autosomes. About two-thirds of XX males contain detectable Y derived sequences. As the amount of Y sequences present varies in different XX males, DNA from these subjects can be used to construct a map of the region around the sex determining gene. Assuming that XX males are usually caused by simple translocation, the sex determining genes cannot be located in the pericentric region. Although conventional genetic analysis of the Y chromosome is difficult, this chromosome is particularly suited to molecular analysis. Paradoxically, the Y chromosome may soon become the best defined human chromosome at the molecular level and may become the model for other chromosomes.

Antibodies, Monoclonal↗
PubMed1985

Cytoskeletal reorganization and plasma membrane fusion in conjugating Tetrahymena.

The conjugation junction of Tetrahymena is the specialized site where plasma membrane fusion occurs between two cells of complementary mating types. The junction is constructed through a series of cooperative interactions and morphogenetic steps. A contact-mediated interaction between free-swimming, sexually mature and mating-competent cells of two complementary mating types induces a morphological transformation of the anterior tips. Cells then join in pairs aligned by the apposition of their modified tips. Thin sections show that the plasma membranes of the tips are separated by approximately 500 A of extracellular space, in which some strands of matrix material can be identified. The cytoplasmic face of the membrane is in contact with a junction-specific thick layer of electron-dense material. At hundreds of independent sites in this junction plasma membranes fuse in a limited manner, thereby establishing hundreds of separate membrane-ensheathed cytoplasmic channels that connect the two cells. At the same locations the thick submembrane layer is interrupted. Consequently, the junction appears to be a structure that is perforated with hundreds of pores. This study poses the question of whether the junction's submembrane layer is, or includes, a skeletal element. Cells were extracted with the non-ionic detergent Triton X-100 under conditions that yield cytoskeletal frameworks (CFs) that maintain the morphological integrity of the cells. The CFs include chromatin and also cortical structures such as microtubule bands, basal bodies, ciliary axonemes, kinetodesmal fibres and fibrillar epiplasm. CFs of conjugant pairs are also paired, indicating that the junction contains a skeletal element that is responsible for integrating the individual CFs into a higher-order complex. At the ultrastructural level the skeletal structure of the junction includes membrane lamina and a submembrane scaffold, residues of the plasma membrane and thick submembrane layer, respectively, both of which are interrupted at the pores. However, the two separate scaffolds are joined at the rims of the pores. This provides a means by which the separate CFs become integrated. On the basis of images of junctional CFs, which show interruptions of the scaffold without concomitant membrane fusion, but where laminae are pressed close together, a specific model of membrane fusion is proposed. According to this model, the submembrane skeletal scaffold regulates membrane fusion by limiting its occurrence, and the extent of its occurrence.

Animals↗
PubMed1984

Cosmid clones derived from both euchromatic and heterochromatic regions of the human Y chromosome.

Clones containing sequences derived from the human Y chromosome have been isolated from cosmid libraries of a human-mouse hybrid cell line. These libraries were constructed in the new expression vectors Homer V and Homer VI. The collection of cosmids isolated is enriched for unique sequence DNA and only a few of the cosmids contain the tandemly repeated sequences which constitute a major portion of the Y chromosome. Three cosmids have been studied in detail. One cosmid shows extensive homology over at least 20 kb with the long arm of the X chromosome; this homology is outside the predicted homology region required for sex chromosome pairing. The other two clones contain unique sequences specific to the Y chromosome and both map to the heterochromatic region of the Y chromosome long arm.

Animals↗
PubMed1984

CT diagnosis of actinomycosis of the neck.

Actinomycosis is an unusual bacterial infection that most often affects the head and neck region. Abscesses occasionally associated with a draining sinus may result secondary to extensive tissue destruction. We report the CT appearance in a case of actinomycosis of the neck. A thick walled enhancing mass with a low attenuation center was identified between the sternocleidomastoid muscle and the strap muscles of the neck. Enhancement of the adjacent muscles was present. Surgery confirmed an abscess with inflammation of the adjacent muscle. Histologic examination of the specimen showed the presence of multiple yellow (sulfur) granules containing Actinomyces. Computed tomography correctly determined the extent of the mass and lack of involvement of the deep structures of the neck.

Abscess↗
PubMed1984

Regional localization of 3 Y-derived sequences on the human X and Y chromosomes.

The structure of the Y chromosome and the relationship between the human sex chromosomes have been studied using Y-derived sequences cloned in cosmids. Two probes recognize different unique sequences which map to the heterochromatic part of the long arm of the Y chromosome. A third sequence is shared by the long arm of the X chromosome and the euchromatic part of the Y chromosome. Thus homology between the sex chromosomes occurs outside the pairing region.

Animals↗
PubMed1984

Histamine and slow reacting substance in acid-induced pneumonitis.

Acid pneumonitis was produced in 18 dogs by the tracheal instillation of 3 ml/kg 0.1 N hydrochloric acid. Arterial and mixed venous oxygen tension, static compliance and pulmonary capillary wedge pressure were measured during a 2-hour observation period. Plasma histamine (measured by the enzymatic isotopic assay) increased from 1.7 +/- 0.2 ng/ml (mean +/- SE) before acid injury to 13.5 +/- 1.9 ng/ml after injury (p less than 0.05). In one group of 7 control dogs, 3 ml/kg of normal saline produced no increase in plasma histamine. Pulmonary edema secretions from acid injured animals had a histamine level of 30.3 +/- 3.8 ng/ml and slow reacting substance was detected in 7 of 11 animals. The slow reacting substance was an antihistamine-resistant, ethanol extractable substance that contracted guinea pig ileum. Lung weight-body weight ratio PaO2, and static compliance were different with acid pneumonitis compared to controls. Total protein was not different in the tracheal secretions compared to plasma. We conclude that histamine and slow reacting substance are released in this animal model of acid pneumonitis and may be important in the pathogenesis of the lung injury.

Animals↗
PubMed1983

Mechanical properties of the plasma membrane of isolated plant protoplasts : mechanism of hyperosmotic and extracellular freezing injury.

The volume of isolated protoplasts of rye (Secale cereale L. cv Puma) in a suspending solution at constant concentration is shown to be negligibly changed by tensions in the plasma membrane which approach that tension necessary to lyse them. This allows a detailed investigation of the plasma membrane stress-strain relation by micropipette aspiration.Over periods less than a second, the membrane behaves as an elastic two-dimensional fluid with an area modulus of elasticity of 230 millinewtons per meter. Over longer periods, the stress-strain relation approaches a surface energy law-the resting tension is independent of area and has a value of the order 100 micronewtons per meter. Over longer periods the untensioned area, which is defined as the area that would be occupied by the molecules in the membrane at any given time if the tension were zero, increases with time under large imposed tensions and decreases under sufficiently small tension. It is proposed that these long term responses are the result of exchange of material between the plane of the membrane and a reservoir of membrane material. The irreversibility of large contractions in area is demonstrated directly, and the behavior of protoplasts during osmotically induced cycles of contraction and expansion is explained in terms of the membrane stress-strain relation.

Journal Article↗
PubMed1982

Elastic response of bilayers with intrinsic proteins.

Intrinsic membrane proteins affect the ordering of neighbouring lipid chains. We have used a model of protein-lipid interactions in bilayers proposed by Owicki et al. (Owicki, J.C., Springgate, M.W. and McConnell, H.M. (1978) Proc. Natl. Acad. Sci. U.S.A. 75, 1616-1619) to show that near the lipid phase transition this effect may significantly increase the magnitude of a membrane's lateral compressibility (or correspondingly, decrease the magnitude of the membrane's elastic moduli).

Animals↗
PubMed1982

Lateral tensions and pressures in membranes and lipid monolayers.

The effects of lateral tension on the properties of membranes are often explained in comparison with analogous experiments on monolayers, which yield more detailed data. To calculate the effects of changes in tension on the composition of, or incorporation of amphiphiles into membranes we examine (i) the fidelity of the monolayer analogy, (ii) the range of possible tensions in a membrane, and the way in which tensions arise and (iii) the equilibrium partitioning of amphiphiles between aqueous solution and a bilayer under tension. We argue that, at the same areas per molecule, a monolayer at an n-alkane/water interface is a closer analogy of the lipid bilayer than a monolayer at an air/water interface. Next, we show from a thermodynamic argument that changes in membrane tension can affect the absorption of very large amphiphiles such as proteins, but that physiological tensions are unlikely to affect the absorption of lipids or drugs. Finally we consider the possibility that the measured bulk tension in a complicated membrane such as that of the erythrocyte may be larger than the local tension in the fluid mosaic portions, and suggest a model which explains the ability of the erythrocyte membrane to withstand much higher tensions than other biological membranes and lipid bilayers.

Lipid Bilayers↗
PubMed1981

The stress-strain relation of the plasma membrane of isolated plant protoplasts.

Over periods of up to a few seconds the plasma membrane of isolated rye protoplasts behaves elastically with an area modulus of 230 mN x m-1. Over longer periods, the area increases with time under large tension and decreases under sufficiently small tension, suggesting that material is incorporated into or depleted from the plane of the membrane.

Cell Membrane↗