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Biomedical subjects

M E Clark

Publications and source records attributed to M E Clark.

At least 55 records · Page 3Linked to original sources
PubMed1990

AIDS prevention: legislative options.

This article reviews legislative options to prevent the transmission of HIV infection. It distinguishes between pre-exposure measures designed to prevent initial exposure, and post-exposure measures aimed at preventing infected individuals from exposing others. Part I identifies education as the key component of a comprehensive prevention program, and reviews options for pre-exposure education programs designed to avoid or minimize exposure. Part II reviews post-exposure prevention measures, focusing on reporting and contact tracing provisions. Mandatory reporting by name of individuals testing HIV positive and mandatory contact tracing are opposed as counterproductive prevention measures; voluntary partner notification is supported. Part III examines various prevention efforts for settings where there may be either a real or perceived risk of transmission of HIV infection. Part IV sets out conclusions.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Mapping of immunogenic regions of human T cell leukemia virus type I (HTLV-I) gp46 and gp21 envelope glycoproteins with env-encoded synthetic peptides and a monoclonal antibody to gp46.

Antigenic sites on human T cell leukemia virus type I (HTLV-I) gp46 and gp21 envelope glycoproteins that are immunogenic in man were studied with envelope gene (env)-encoded synthetic peptides and a mAb to HTLV-I gp46 envelope glycoprotein. Antibodies in 78% of sera from HTLV-I seropositive subjects reacted with synthetic peptide 4A (amino acids 190 to 209) from a central region of HTLV-I gp46. Human anti-HTLV-I antibodies also bound to synthetic peptides 6 (29% of sera) and 7 (18% of sera) from a C-terminal region of gp46 (amino acids 296 to 312) and an N-terminal region of gp21 (amino acids 374 to 392), respectively. mAb 1C11 raised to affinity-purified HTLV-I gp46 reacted with gp46 external envelope glycoprotein and gp63 envelope precursor in immunoblot assay and also bound to the surface of HTLV-I+ cells lines HUT-102 and MT-2. Antibody 1C11 did not react with HTLV-II or HIV-infected cells or with a broad panel of normal human tissues or cell lines. In competitive RIA, anti-gp46 antibody 1C11 was inhibited from binding to gp46 either by antibodies from HTLV-I seropositive subjects or by HTLV-I env-encoded synthetic peptide 4A, indicating that 1C11 bound to or near a site on gp46 within amino acids 190 to 209 also recognized by antibodies from HTLV-I-seropositive individuals. When tested in syncytium inhibition assay, mAb 1C11 did not neutralize the infectivity of HTLV-I. Thus, HTLV-I infection in man is associated with a major antibody response to a region of gp46 within amino acids 190 to 209 that is on the surface of virus-infected cells.

Amino Acid Sequence↗
PubMed1989

Natural and surgically imposed anastomoses of the circle of Willis.

The efficacy of the circle of Willis as a flow equalizer is well known. Most cerebral macrovasculatures also contain other natural anastomoses which are activated in times of stenotic stress. For the past several decades, neurosurgeons have surgically augmented the cerebral network with additional vessels which further increase the flow of blood to a defrauded region of the brain. It is desirable to know quantitatively what role these anastomoses play in the delivery of blood. Apart from computer simulation, such knowledge remains out of reach to the medical community but with modern simulation techniques, a wealth of information can be made available. This paper presents both time-dependent and period-averaged results of a detailed study of cerebral anastomoses. Four different models of the macrovasculature in the circle of Willis vicinity have been developed, two of which contain an extracranial-intracranial (EC-IC) anastomosis. Five cases were developed to show how the amount of blood flow is related to the sizes of the anastomoses. Since the EC-IC bypass is only marginally beneficial in those patients whose cerebral circulations are well-equipped with naturally occurring anastomotic vessels, procedures should be developed to screen for their presence or absence. The fluid mechanics associated with the EC-IC bypass operation dictate a beneficial result. Since the surgical procedures fail to consistently show reduction in risk even when good grafts have been made, there is an enigma in the study group results.

Cerebrovascular Circulation↗
PubMed1988

AIDS-related dementia: a case report of rapid cognitive decline.

Little is known psychometrically about the pattern of cognitive decline associated with acquired immunodeficiency syndrome (AIDS)-related dementia. Pre- and posttest results are presented to illustrate a case example of rapid cognitive decline. Increased psychometric assessment is recommended with additional examination of inconsistent results, which may be dismissed mistakenly as related to psychiatric symptoms. Implications for clinical practice and the role of the psychologist are discussed.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Type-specific neutralization of the human immunodeficiency virus with antibodies to env-encoded synthetic peptides.

A synthetic peptide (SP-10-IIIB) with an amino acid sequence [Cys-Thr-Arg-Pro-Asn-Asn-Asn-Thr-Arg-Lys-Ser-Ile-Arg-Ile-Gln-Arg-Gly-Pro -Pro-Gly-(Tyr); amino acids 303-321] from the human immunodeficiency virus (HIV) isolate human T-cell lymphotropic virus type III (HTLV-III) HTLV-IIIB envelope glycoprotein gp120 was coupled to tetanus toxoid and used to raise goat antibodies to HIV gp120. Goat anti-SP-10-IIIB serum bound to the surface of HTLV-IIIB-infected CEM T cells but not to the surface of HTLV-IIIRF-infected or uninfected CEM T cells. Anti-SP-10-IIIB antibodies also selectively bound to gp120 from lysates of HTLV-IIIB cells in immunoblot assays. Twenty-one percent of sera (28 of 175) from patients seropositive for HIV contained antibodies that reacted with SP-10-IIIB in RIA. Human anti-SP-10-IIIB antibodies affinity purified from acquired immunodeficiency syndrome (AIDS) patient serum bound to HTLV-IIIB-infected cells and immunoprecipitated gp120. Goat antibodies to SP-10-IIIB neutralized HTLV-IIIB (80% neutralization titer of 1/600), inhibited HTLV-IIIB-induced syncytium formation, but did not neutralize HIV isolates HTLV-IIIRF or HTLV-IIIMN or inhibit syncytium formation with these isolates. Also, goat antiserum to an homologous synthetic peptide [SP-10-IIIRF(A), (Cys)-Arg-Lys-Ser-Ile-Thr-Lys-Gly-Pro-Gly-Arg-Val-Ile-Tyr] from gp120 of HIV isolate HTLV-IIIRF inhibited syncytium formation by HTLV-IIIRF, but did not inhibit syncytium formation by HTLV-IIIB or by HTLV-IIIMN. Thus, the amino acid sequences of SP-10-IIIB and SP-10-IIIRF(A) define homologous regions of gp120 that are important in type-specific virus neutralization. The identification of these type-specific neutralizing epitopes should facilitate the design of a polyvalent, synthetic vaccine for AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Inducible Ig heavy chain switching in an IgM+ Ly-1 B cell line. Evidence for a state of switch commitment.

We have analyzed the pattern of immunoglobulin (Ig) heavy chain isotype secretion in AJ9, a cloned, IgM+ murine B lymphocyte cell line. Upon induction by a variety of lymphokines and polyclonal B-cell activators, AJ9 cells express multiple subclasses of IgG and IgA in addition to IgM. In certain cases, mature isotype is restricted--e.g., IL-5 predominantly elicits production of IgG2 and IgA, a restriction also observed in short-term lymphocyte cultures. In other cases (e.g., anti-IgM plus 8-mercaptoguanosine, a polyclonal B-cell activator) production of mature isotypes is unrestricted. Under optimal conditions, only a low abundance of secreted Ig and low frequency of secreting cells (less than 0.5%) were detected. A serial cloning assay was devised to define the pattern of isotype switching in induced cells and their progeny. We expected to observe a progressive limitation of progeny to expression of single mature isotypes. Surprisingly, nearly all subclones of the induced cells were found to produce a range of mature isotypes. Sequential cloning in basal medium revealed that this induced phenotype persisted for more than a month (greater than 40 generations). Throughout this period, the abundance of mature isotype production remained low, and membrane Ig was exclusively of the IgM isotype. We interpret this induced response to reflect an intermediate state of B-cell differentiation, in which cells become committed to the switching process, but are not adequately stimulated to efficiently complete the process required for expression of mature isotypes. These findings are discussed in regard to the control of the switching process, and their possible relevance to the memory state of B cells.

Animals↗
PubMed1987

Purification of envelope glycoproteins of human T cell lymphotropic virus type I (HTLV-I) by affinity chromatography.

The external envelope glycoprotein (gp46) and transmembrane glycoprotein (gp21) of human T-cell lymphotropic virus type I (HTLV-I) were isolated from lysates of HTLV-I-infected HUT-102 cells by affinity chromatography. Fifty ml aliquots of packed HUT-102 cells were extracted with 1% Triton X-100, and lysates were treated sequentially with an affinity column containing IgG from an HTLV-I+ human subject followed by chromatography of the bound fraction over a lentil lectin column. The identity of the purified envelope proteins was confirmed with a human monoclonal antibody (0.5 alpha) to gp46 and with rabbit antisera raised to a synthetic peptide from the C-terminus of gp21. Affinity-purified envelope glycoproteins were bound to microtiter wells and used in radioimmunoassay to detect murine and human anti-envelope antibodies to gp46 and gp21 molecules.

Antibodies, Viral↗
PubMed1987

A conserved region at the COOH terminus of human immunodeficiency virus gp120 envelope protein contains an immunodominant epitope.

A highly immunogenic epitope from a conserved COOH-terminal region of the human immunodeficiency virus (HIV) gp120 envelope protein has been identified with antisera from HIV-seropositive subjects and a synthetic peptide (SP-22) containing 15 amino acids from this region (Ala-Pro-Thr-Lys-Ala-Lys-Arg-Arg-Val-Val-Gln-Arg-Glu-Lys-Arg). Peptide SP-22 absorbed up to 100% of anti-gp120 antibody reactivity from select HIV+ patient sera in immunoblot assays and up to 79% of serum anti-gp120 antibody reactivity in competition RIA. In RIA, 45% of HIV-seropositive subjects had antibodies that bound to peptide SP-22. Human anti-SP-22 antibodies that bound to and were eluted from an SP-22 affinity column reacted with gp120 in RIA and immunoblot assays but did not neutralize HIV or inhibit HIV-induced syncytium formation in vitro, even though these antibodies comprised 70% of all anti-gp120 antibodies in the test serum. In contrast, the remaining 30% of SP-22 nonreactive anti-gp120 antibodies did not react with gp120 in immunoblot assays but did not react in RIA and neutralized HIV in vitro. Thus, approximately 50% of HIV-seropositive patients make high titers of nonneutralizing antibodies to an immunodominant antigen on gp120 defined by SP-22. Moreover, the COOH terminus of gp120 contains the major antigen or antigens identified by human anti-gp120 antibodies in immunoblot assays.

Acquired Immunodeficiency Syndrome↗
PubMed1987

The case against compulsory casefinding in controlling AIDS--testing, screening and reporting.

The spread of acquired immune deficiency syndrome (AIDS) demands a comprehensive and effective public health response. Because no treatment or vaccine is currently available, traditional infection control measures are being considered. Proposals include compulsory testing and screening of selected high risk populations. The fairness and accuracy of compulsory screening programs depend upon the reliability of medical technology and the balancing of public health and individual confidentiality interests. This Article proposes criteria for evaluating compulsory testing and screening programs. It concludes that voluntary identification, education, and counselling of infected persons is the most effective means of encouraging the behavioral changes that are necessary to halt the spread of AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Purification and properties of Clostridium difficile cytotoxin B.

Toxin B, a potent cytotoxin produced by Clostridium difficile, was purified to homogeneity from 6-day broth cultures of a toxigenic isolate. Cytotoxin was purified approximately 4000-fold by sequential ammonium sulfate precipitation, DEAE-Sepharose chromatography, and high performance liquid chromatography on a Mono Q anion-exchange column. The molecular weight of reduced purified toxin was 50,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, compared to 150,000 for unreduced toxin. Dose-response studies indicated that subpicogram concentrations of purified toxin caused rounding of approximately 20,000 IMR-90 fibroblasts. The phenomenon of cell rounding caused by toxin B was correlated with the ratio of globular to filamentous actin in fibroblasts as measured by two techniques. The toxin caused a significant increase in the ratio of globular to filamentous actin which was nearly completed prior to the onset of rounding. We conclude that cell rounding of fibroblasts exposed to toxin B is related to an increase in the ratio of globular to filamentous actin which is produced by small numbers of toxin molecules/cell.

Actins↗
PubMed1986

Cardiovascular defects in rat embryos cultured on serum from rats chronically exposed to phenytoin.

Headfold-stage rat embryos were cultured for 48 hours on serum from rats chronically exposed to phenytoin for periods as long as from conception until 11 months of age. Serum from phenytoin-exposed rats caused approximately 50% of the cultured rat embryos to develop cardiovascular defects as compared to 12% for controls. These morphological abnormalities included hemorrhaging of blood vessels within the embryo, pericardial edema, and absence of yolk sac circulation. Neither serum glucose nor phosphate levels nor serum osmolality were appreciably affected by phenytoin treatment. However, serum protein concentration was reduced in rats exposed to phenytoin as compared to controls. An absence of the serum protein hemopexin was associated with the reduction in serum protein levels but did not appear to be responsible for the observed cardiovascular defects.

Animals↗
PubMed1985

The structure of two distinct pancreatic amylase genes in mouse strain YBR.

The amylase complex on mouse chromosome 3 encodes both salivary and pancreatic amylase. It appears that one active gene is present for salivary amylase, whereas pancreatic amylase in some strains is coded by at least 4, and perhaps by more than 10, genes. Strain YBR is different from other strains in that it produces twice as much salivary amylase. Pancreatic amylase in YBR is present as two different protein forms, A beta and B beta, the sum of which amounts to only one-third of that in, for instance, strain A/J. YBR chromosomal DNA was cloned in phage gamma, followed by restriction and heteroduplex analysis of recombinant phages carrying amylase genes. Among 32 phage isolates, 5 carried parts of the salivary amylase sequence. The remaining phage isolates contained pancreatic amylase-like sequences and represented three nonoverlapping genomic regions, i.e., one of 34 kb containing a complete gene, PAN-II beta; another of 41 kb with a complete but different gene, PAN-I beta, plus a truncated gene, PAN-psi 1; and finally, one of 23 kb with another truncated gene, PAN-psi 2. Parts of the amino acid sequence of A beta and B beta have previously been determined, and we report here the sequencing of a 4-kb DNA fragment from Pan-II beta which establishes that this gene codes for B beta.

Amino Acid Sequence↗
PubMed1985

A circle of Willis simulation using distensible vessels and pulsatile flow.

The development of a one-dimensional numerical (finite-difference) model of the arterial network surrounding the circle of Willis is described based on the full Navier-Stokes and conservation of mass equations generalized for distensible vessels. The present model assumes an elastic wall defined by a logarithmic pressure-area relation obtained from the literature. The viscous term in the momentum equation is evaluated using the slope of a Karman-Pohlhausen velocity profile at the vessel boundary. The afferent vessels (two carotids and two vertebrals) are forced with a canine physiologic pressure signature corresponding to an aortic site. The network associated with each main efferent artery of the circle is represented by a single vessel containing an appropriate amount of resistance so that the mean flow through the system is distributed in accordance with the weight of brain irrigated by each vessel as determined from a steady flow model of the same network. This resistance is placed a quarter wave-length downstream from the heart to insure proper reflection from the terminations, where the quarter wavelength is determined using the frequency corresponding to the first minimum on an input impedance-frequency diagram obtained at the heart. Computer results are given as time histories of pressure and flow at any model nodal point starting from initial conditions of null flow and constant pressure throughout the model. Variations in these pressure and flow distributions caused by the introduction of pathologic situations into the model illustrate the efficacy of the simulation and of the circle in equalizing and redistributing flows in abnormal situations.

Cerebrovascular Circulation↗
PubMed1983

Stenosis severity effects for unbalanced simple-pulsatile bifurcation flow.

A numerical finite-difference analysis is made of a plane simple-pulsatile flow past a symmetrical bifurcation which contains an asymmetrical smooth-contoured stenosis in the trunk. In essence, such a situation could represent a stenosed common carotid artery immediately upstream from the carotid junction. The flow is unbalanced; two-thirds of it exits or enters through the lower branch. The effect on various flow parameters of the stenosis itself and on changes in its severity is investigated by comparing the results for a severe stenosis, a mild stenosis, and no stenosis. The simple-pulsatile forcing function is specified in terms of an oscillatory and a steady Karman number. To obtain a significant amount of backflow, the oscillatory trunk Karman number is taken as 1000 compared to the steady value of 250. The frequency of oscillation is stipulated by a trunk Stokes number of 10 pi. The numerical procedures utilize the vorticity-transport version of the Navier-Stokes governing equations. A non-orthogonal coordinate transform allows the calculations to be made in a rectangular grid where the central difference expressions are easily applied. The results are presented in terms of both kinematic and kinetic parameters. The variation in the basic kinematic variables of stream function and vorticity is shown by temporal sequences of contour plots at times of peak flow and during the flow reversal stages as well as by several velocity vector plots. Kinetic results are given in terms of the temporal variation in shear stresses along boundaries. The peak shears are found to occur at the zenith of the stenosis at times of peak flow: the value for the severe stenosis is twice as large as that for the mild stenosis. The midline pressure distribution in the trunk and the centerline pressure distributions in the branches are also included.

Carotid Arteries↗
PubMed1982

Living with water stress: evolution of osmolyte systems.

Striking convergent evolution is found in the properties of the organic osmotic solute (osmolyte) systems observed in bacteria, plants, and animals. Polyhydric alcohols, free amino acids and their derivatives, and combinations of urea and methylamines are the three types of osmolyte systems found in all water-stressed organisms except the halobacteria. The selective advantages of the organic osmolyte systems are, first, a compatibility with macromolecular structure and function at high or variable (or both) osmolyte concentrations, and, second, greatly reduced needs for modifying proteins to function in concentrated intracellular solutions. Osmolyte compatibility is proposed to result from the absence of osmolyte interactions with substrates and cofactors, and the nonperturbing or favorable effects of osmolytes on macromolecular-solvent interactions.

Amino Acids↗
PubMed1982

Water in barnacle muscle. IV. Factors contributing to reduced self-diffusion.

The relative self-diffusion coefficients D/Do, of water in various solutions, in fresh barnacle muscle fibers, and in membrane-damaged fibers equilibrated with several media have been estimated from NMR relaxation rates in the presence of applied field gradients. A model has been developed to account for the contributions to the observed reduction in D/Do from small organic solutes, and from the hydration and obstruction effect of both soluble macromolecules and myofilament proteins. Intracellular ions do not affect D/Do, but all tested organic solutes do. Solute effects are additive. When artificially combined in the proportions found in barnacle muscle ultracentrifugate (measured D/Do = 0.77), organic acids, small nitrogenous solutes, and proteins give D/Do = 0.77. After correcting the D/Do measured in fibers for this value, we calculate the myofilament hydration, Hm, in fresh muscle to be 0.65 g H2O/g macromolecule. Only in membrane-damaged fibers, highly swollen by salt-rich media, was this significantly increased. Because our earlier NMR relaxation measurements indicate only 0.07 g H2O bound/g myofilament protein, we conclude that the "hydration" water measured by reduction of D/Do cannot be described by stationary layers of water molecules; instead, we propose that nonpolar groups on the proteins cause extensive, hydrophobically-induced interactions among a large fraction of solvent molecules, slowing their translational motion.

Animals↗