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PubMed1988

The role of hyaluronic acid in inflammation and wound healing.

We have previously hypothesized that hyaluronic acid (HA) and fibrin specifically interact and help orchestrate the early stages of the inflammatory response and wound healing (J. Theoretic. Biol. 119, 219, 1986). In the present work we have extended studies to confirm this prediction. Several approaches were used to show that human fibrinogen specifically binds to hyaluronic acid. In addition, this latter glycosaminoglycan greatly stimulated the in vitro formation of fibrin clots induced by thrombin. The presence of hyaluronic acid also altered the structure of the final fibrin gel. Removal of circulating hyaluronic acid in blood is therefore probably vital in order to maintain normal haemostasis. Evidence is presented to suggest that an endocytic receptor recycling process is responsible for the ability of liver endothelial cells to perform this function and remove HA from the blood. Although hyaluronic acid levels are initially low in a blood clot, the proposed wound-healing model explains why and how HA levels increase and the functional and structural significance of this polysaccharide during wound healing.

Animals↗
PubMedDate not supplied

[Plasmodium falciparum malaria attacks with low or negative parasitemia on returning from areas of endemic resistance to 4-aminoquinolines].

Twelve recent cases of Plasmodium falciparum malaria presented with unusual clinical and laboratory features. All patients had regularly been taking adequate doses of amino-4-quinolines as prophylaxis. In most cases the symptoms were mild as compared with those in a group of 20 control patients with typical malaria. More surprisingly, parasitaemia was either negative or very weakly positive (less than 1000 infested erythrocytes per mm3). All cases occurred in people returning from areas in which resistance of P. falciparum to these drugs is endemic. Diagnostic problems could be solved in most patients by new immunological techniques relying on the detection of parasitized erythrocytes and plasmodium antigens using a battery of monoclonal antibodies. A physiopathological model explaining why parasitaemia is negative in such cases is suggested.

Amodiaquine↗
PubMedDate not supplied

The functions of eosinophils.

The observations summarized above were made because of the striking associations between peripheral blood eosinophilia and various human diseases. Clinicians caring for patients with asthma have known for years that peripheral blood eosinophilia and marked bronchial and sputum eosinophilia are associated with asthma. As a consequence of studies using the eosinophil granule MBP, we are now able to postulate that eosinophils damage bronchial epithelium during the course of asthma. This model proposes that eosinophils are attracted into bronchial epithelium and degranulate, releasing toxic cationic proteins which cause desquamation and damage to bronchial epithelium. This model explains many of the features of bronchial asthma, but it leaves open the question of the mechanism(s) for eosinophil attraction to the bronchial epithelium. The studies of eosinophils in cutaneous diseases have led to the hypothesis that the eosinophil loses its morphologic integrity in the skin either by degranulation and loss of its characteristic granules or by frank death of the cell. In either event, there is a strong association between deposition of eosinophil granule MBP and cutaneous oedema. Finally, a molecule indistinguishable from eosinophil granule MBP is found in the human placenta.

Animals↗
PubMed1987

Sociobiology of addiction in adolescence.

The authors review the application of evolutionary theory to the study of social, including parental and reproductive, behavior through a system of ideas known as sociobiology. Using this approach they suggest that evolutionary models predict the conflicts of adolescence. They develop a model explaining the genetic association of alcoholism and the tendency for antisocial behavior, and suggest why such behaviors most commonly begin in adolescence. Potential implications for the treatment of adolescent substance abusers are explored.

Adolescent↗
PubMed1982

A study of added GM-CSF independent granulocyte and macrophage precursors in mouse spleen infected with myeloproliferative sarcoma virus (MPSV).

A subpopulation of granulocyte and macrophage precursors (GM-CFUc) differentiating in the agar colony technique of Bradley and Metcalf into mature granulocytes and macrophages, without the addition of granulocyte and macrophage colony stimulating factor (GM-CSF), can be detected in MPSV infected mice. These precursors were detected 5 days after virus infection, reaching a maximal concentration of 1/10,000 spleen or bone marrow cells, 25 days after viral infection. The number of the added GM-CSF independent GM-CFUc was linearly correlated with the number of seeded MPSV hematopoietic cells. No GM-CSF producing cells could be detected in the MPSV spleen using normal bone marrow GM-CFUc as responder cells. Study of the GM-CSF sensitivity of the GM precursors has demonstrated the existence of two GM-CFUc populations in the MPSV spleen: a) a GM-CSF dependent population with a GM-CSF sensitivity similar to that of normal GM-CFUc b) a GM-CFUc population which differentiated in the absence of detectable amount of GM-CSF and of which differentiation was not affected by the addition of progressive amounts of GM-CSF. A possible model explaining these results is proposed.

Animals↗
PubMed1983

[Epileptic absences. Studies on the structure, pathophysiology and clinical course of the seizure].

The temporal structure of absence symptoms of 59 patients--investigated by subtilized polygraphic video documentation technique--discloses a global functional scheme of motor activity directed from cranial parts of the body--like the ocular region--towards caudal parts. In analogy to the Jacksonian march of partial elementary motor seizures these findings are interpreted as a march of generalizing seizure activity of absence type. Its recognition allows to understand many motor as well as so-called "automatic" absence symptoms as correlated elements of a general organization plan. The development of a nuclear-layer model explains the fact, that in short-lasting absences often only ocular symptoms occur whereas in long lasting absences oral automatisms or motor activities of the extremities as well as gestural automatisms become manifest. New techniques of intensive seizure monitoring are carried out during therapy in patients with absences.

Automatism↗
PubMed1978

Hemoperfusion removal of digoxin from dogs.

Removal of digoxin by XAD-4 hemoperfusion columns was tested after four dogs were given 0.06 mg/kg of digoxin i.v. Dogs were perfused for 4 to 5 hr at a flow of 105 ml/min through a 100 gm XAD-4 column 16 hr after the dose. Pharmacokinetic analysis of digoxin levels was performed with a three-compartment model. The apparent postdistribution t1/2 was 16.0 +/- 2.9 (S.D.) hr and decreased to 7.1 +/- 2.1 hr during perfusion. Digoxin perfusion clearance was 46 ml/min. An average of 51 microgram of digoxin was recovered from used columns. CP of digoxin calculated from the total R was 127.5 +/- 13 ml/min or 2.3 times greater than plasma flow. With the use of 3H-digoxin, canine blood was found to contain 2.5 times as much digoxin as did plasma. After perfusion there was an increase in serum digoxin levels in all dogs. Computer analysis showed that the increase in plasma digoxin levels immediately after hemoperfusion occurred because the central compartment, which was depleted of digoxin during hemoperfusion, was refilled from peripheral compartments. This study demonstrated that (1) XAD-4 hemoperfusion doubles the rate of removal of digoxin from dogs, (2) dog whole blood contains more than twice as much digoxin than does plasma, so that hemoperfusion clearance exceeds plasma flow, and (3) a multicompartmental pharmacokinetic model explains the increase in serum digoxin concentrations observed at the completion of hemoperfusion.

Animals↗
PubMedDate not supplied

[Genetic study of paradoxical sleep in mice. Connection with coloration genes].

The study of Paradoxical Sleep (PS) from 94 male mice belonging to five inbred strains: C57BR/cdOrl (BR), BALB/cOrl (C), AKROrl, A/JOrl (A/J) and C57BL/6-c2J (B6-c2J), reciprocal F1 hybrids between BR and C strains and backcrosses between F1 hybrids and BR or C was carried out. The results showed that 1) night PS duration was independent from that of day PS; 2) C type of PS seemed to be dominant over BR type; 3) C type is linked to the albino gene; and 4) the albino gene, per se, is not involved in PS regulation. From these results a two locus model was elaborated. This model explains most of the results. The nature of such a genetic support was discussed.

Animals↗
PubMed1995

Assortative mating: sex differences in mate selection for married and unmarried couples.

We studied assortative mating for age, nationality, educational level, and occupational level in married and unmarried parents to test evolutionary models explaining mate selection among humans. We used the marriage and birth registers of the Venezuelan population to compare recently married, fertile married, and fertile unmarried couples. The results show significant assortative mating for all variables, but the results are strongest for age and education. These data suggest that (1) selection criteria based on age vary along the life cycle and differ between married and unmarried couples; (2) male's socioeconomic status is more related to the availability of younger females among unmarried couples compared with married couples, except for young couples; and (3) female selection for better (more educated and/or better employed) mates is stronger among married couples, whereas male selection for younger females or those showing actual reproductive potential is stronger among unmarried couples.

Adolescent↗
PubMedDate not supplied

[Charcot and hysteria].

Charcot's work on hysteria has always been controversial. All his attitudes, whether on the theory of the ovary, the hysteroepileptic seizure or the use of hypnosis, have always been charicatured, misunderstood and separated from the wider context of his overall approach. Rereading Charcot's works shows that he developed his approach progressively over a period of more than 20 years before coming to his psychological model of hysteria. This model explains the formation of the symptom and the hysterical conversion via a mechanism of being ignorant of the motor representation. This concept has never been disproven and remains the only theory explaining the formation of the hysteria symptom. Based on Charcot's fundamental contribution, Freud and Janet further developed their work on the psychopathology of hysteria.

History, 19th Century↗
PubMed1994

Evaluation of a German version of the physical dimensions of the Health Assessment Questionnaire in patients with rheumatoid arthritis.

OBJECTIVE: Our objective was to translate and adapt the disability section of the health assessment questionnaire (HAQ) into German (HAQ-G) to suit Swiss-German conditions and to test its metric properties, reliability, and validity. METHODS: We tested 62 consecutive patients with rheumatoid arthritis (RA) attending the outpatient Clinic of the Department of Rheumatology, University Hospital Zurich. All patients fulfilled the American Rheumatism Association 1987 revised criteria for RA. The translation was done by 2 translators aware of the objective of the questionnaire and some questionable items were discussed and resolved in a panel by 4 rheumatologists including one bilingual clinical researcher. Test-retest reliability was assessed with Pearson's correlation coefficient on the scores of 2 questionnaire mailed in a 10-day interval. The internal consistency was assessed with Cronbach's coefficient alpha. To assess the construct validity, we compared the HAQ scores to clinical, laboratory, and radiological variables of disease activity and outcome. To assess criterion validity, we compared physicians' assessment of functional class (observed disability) to the HAQ (referred disability). The content validity was assessed in a multivariate model explaining HAQ scores with a variety of other measurements of disease activity and outcome. RESULTS: The test-retest reliability was 0.94; the internal consistency was 0.92; the criterion validity was 0.76; and correlations with other disease variables ranged from 0.39 (Larsen radiological score) to 0.66 (grip strength). CONCLUSION: The HAQ-G is a reliable and valid instrument for measuring functional disability in a German speaking population with RA.

Aged↗
PubMed1994

Metabolic determinants of the course of coronary artery disease in men.

We examined associations between metabolic variables and changes in coronary artery disease (CAD) in the St. Thomas' Atherosclerosis Regression Study (STARS). The course of CAD over 3 years was measured continually by quantitative coronary angiography, i.e., as the per patient change in the mean absolute width of coronary segments (delta MAWS). The decrease in MAWS (progression of CAD) was significantly correlated with in-trial plasma concentrations of cholesterol (P = 0.002), low-density lipoprotein (LDL) cholesterol (P = 0.001), apolipoprotein B (apoB) (P = 0.008), and lipoprotein(a) [Lp(a)] (P = 0.004); no significant associations were found with high-density lipoprotein (HDL) cholesterol, apoA-I, vitamin E, thyroid hormones, fibrinogen, von Willebrand factor, or post-load plasma glucose and insulin concentrations. By multiple regression analysis, LDL cholesterol was the best predictor of delta MAWS, the adjusted model explaining 22% of the variance (P = 0.04). Thus, in men with symptomatic CAD the most important metabolic predictor of change in CAD is plasma LDL cholesterol, there being no advantage in measuring other variables, in particular, apoB or Lp(a).

Adult↗
PubMed1994

Formation of intersubunit disulfide bonds and properties of the single histidine and cysteine residues in each subunit relative to the decameric structure of cyanase.

Reaction of the single cysteine residue in each subunit of cyanase with certain SH reagents gives an active decameric derivative that dissociates reversibly to an inactive dimer derivative (Anderson, P. M., Johnson, W. V., Korte, J. J., Xiong, X., Sung, Y.-c., and Fuchs, J. A. (1988) J. Biol. Chem. 263, 5674-5680). Reaction of mixed disulfide dimer derivatives of cyanase with dithiothreitol at 0 degree C results in formation of a disulfide bond between the subunits in the dimer. The disulfide dimer was inactive and did not associate to a decamer; the intersubunit disulfide bond could not be formed when the dimers were associated as a decamer. The two SH groups apparently are in close proximity to each other in the dissociated dimer but not when the dimer is associated to a decamer. Substitution of glycine for the cysteine residue or of tyrosine, asparagine, glycine, valine, or leucine for the single histidine residue in each subunit gave mutant enzymes that were active. However, H113N, H113Y, and C83G were unstable at low temperature and/or ionic strength, dissociating reversibly to an inactive dimer. Efficient reassociation required the presence of bicarbonate or cyanate analog. The results are consistent with a proposed single site per subunit model explaining apparent half-site binding of substrates and the requirement of decameric structure for activity.

Base Sequence↗
PubMed1994

The heavy metal subculture and suicide.

The impact of the heavy metal music subculture on suicide has been the subject of much public debate but little scholarly research. The present paper assesses this relationship with data on heavy metal magazine subscriptions and youth suicide in the 50 states. We find that, controlling for other predictors of suicide, the greater the strength of the metal subculture, the higher the youth suicide rate. The music perhaps nurtures suicidal tendencies already present in the subculture. The model explains 51% of the variance in youth suicide.

Adolescent↗
PubMed1993

[Wegener's granulomatosis and ANCA-associated vasculitis: pathogenic role of autoantigens, autoantibodies, and cytokines].

A real explosion of data is seen concerning the detection of autoantibodies collectively known as antineutrophil cytoplasmic antibodies (ANCA) recognizing granule proteins of granulocytes and monocytes. Distinct fluorescence staining patterns result from their diverse substrate specificities, and can even identify several disease entities mainly in the etiopathogenetically unclear group of primary systemic vasculitides (PSV). The well-documented disease specificity of ANCA recognizing proteinase 3 (PR3), and recent in vitro findings concerning the effect of cytokines on immunocompetent cells including the endothelium are the rationale for the presentation of a new model explaining the development of systemic vasculitis.

Autoantibodies↗
PubMedDate not supplied

How much do health care providers know about AIDS?

We sent a survey to more than 8,000 New Jersey health professionals to collect information on their knowledge level, attitudes, and prevention practices relating to the human immunodeficiency virus (HIV) and the acquired immunodeficiency syndrome (AIDS). The surveys were distributed through the mail in three separate waves with a postcard reminder. A total of 2,725 individuals provided completed questionnaires (34% response rate). We assessed the AIDS and HIV-related knowledge level of these health professionals, compared their knowledge levels, and identified variables that predict a high level of knowledge. The overall test scores indicate a definite need for AIDS education among these health professionals; on average, doctors answered 71% of the knowledge items correctly; dentists, 66%; and nurses, 65%. Doctors scored higher than the other health professionals on almost all of the 38 items relating to the epidemiological aspects of HIV, transmission, identification and reporting of HIV disease and AIDS, and assessment of HIV-associated risks. The multivariate regression model explained 24% of the variability in knowledge score (P = .0001) and identified the following independent variables as significant predictors of knowledge score: age, race, marital status, religious beliefs, political orientation, professional group, average number of hours worked each week, experience with HIV+/AIDS patients, knowledge self-assessment, and sources of AIDS information.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

[Amperometric titration of erythrocyte membrane sulfhydryl groups].

The best conditions are selected for amperometric titration of erythrocyte membranes SH-groups by means of silver ions. On the basis of the experimental data, two types of SH-groups according to their capacity of binding Ag+ are found in the membranes. Dynamics of transition of SH-groups of types I into SH-groups of type II is studied. The chemical model explaining the presence of two bends in the course of the membranes amperometric titration curve is created. Calculations were made for the products of R-S-Ag solubility for SH-groups of type I and SH-groups of types I and II as well as for entropy and heat of formation of silver compounds with the membranes sulphydryl groups.

Cell Membrane↗