Biomedical subjects
Publications and source records attributed to R Anderson.
The effects of fasting in the rat on the plasma fibrinogen concentration have been investigated. Fasting for 24-48 hr produced the expected sustained increase (4-5-fold) in the concentrations in the plasma of non-esterified fatty acids, but no accompanying increase in that of fibrinogen was detected.
A peroxidase-independent method for the determination of phagocyte-derived hydrogen peroxide in vitro is described. The method is based on the catalase-inhibitable oxidation of added cysteine. Human blood neutrophils (1 x 10(6)/ml) were coincubated with the myeloperoxidase (MPO) inhibitor, sodium azide (10 micrograms/ml), for 30 min at 37 degrees C followed by addition of phorbol 12-myristate 13-acetate (PMA, 10 ng/ml), a potent activator of membrane-associated oxidative metabolism. After incubation at 37 degrees C the cells were removed and the supernatants aliquoted and incubated with and without catalase (500 U/ml) for 10 min at room temperature followed by addition of cysteine (50 microM). Thereafter the catalase-inhibitable, H2O2-mediated oxidation of added cysteine was assayed spectrophotometrically following the addition of the thiol-reactive agent 5,5'-dithiobis-(2-nitrobenzoic acid), and the H2O2 concentration determined using a standard curve constructed from difference data based on the oxidation of cysteine by H2O2 (0-200 nmol). The average amount of H2O2 produced by 10(6) PMA-activated neutrophils was 47 +/- 7 nmol/30 min. This sensitive assay procedure is likely to be particularly useful for investigating the effects of pharmacological agents and anti-oxidant nutrients on H2O2 production by activated phagocytes, since these agents are generally unsuited for use in peroxidase-based assays.
Death rates among US black men and women under 75 years of age are higher than for their white counterparts. The explanation for this excess risk, though attributed to socioeconomic factors, remains unclear. We calculated mortality rates by family income for blacks and whites in a representative sample of the US population (National Longitudinal Mortality Study). For persons aged less than 65 years of age, mortality rates are lower in those with higher family income for both blacks and whites, and both men and women. However, at each level of income, blacks have higher mortality than whites. Higher levels of family income are also associated with lower death rates from cardiovascular disease, cancer, and deaths from causes other than cardiovascular disease or cancer. After adjustment for income, blacks have higher death rates from each of these three general causes. For subjects below 65 years, the mortality gradient by income is larger than the gradient by race. The differences in mortality rates by race not accounted for by income may be due to other differences such as access to health care, type or quality of medical care, or behavioral risk factors that disadvantage black populations.
We have used the polymerase chain reaction to isolate fragments of Ty1-copia group retrotransposons from a wide variety of members of the higher plant kingdom. 56 out of 57 species tested generate an amplified fragment of the size expected for reverse transcriptase fragments of Ty1-copia group retrotransposons. Sequence analysis of subclones shows that the PCR fragments display varying degrees of sequence heterogeneity. Sequence heterogeneity therefore seems a general property of Ty1-copia group retrotransposons of higher plants, in contrast to the limited diversity seen in retrotransposons of Saccharomyces cerevisiae and Drosophila melanogaster. Phylogenetic analysis of all these sequences shows, with some significant exceptions, that the degree of sequence divergence in the retrotransposon populations between any pair of species is proportional to the evolutionary distance between those species. This implies that sequence divergence during vertical transmission of Ty1-copia group retrotransposons within plant lineages has been a major factor in the evolution of Ty1-copia group retrotransposons in higher plants. Additionally, we suggest that horizontal transmission of this transposon group between different species has also played a role in this process.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
This study investigated the relationship between two dimensions of anger-hostility--the expression of anger-hostility and the experience of anger-hostility--and cardiovascular reactivity in provoked and angered men. A serial subtraction task was administered to 41 male undergraduates who were provoked and angered. A measure of the expression of anger-hostility correlated positively and significantly with systolic and diastolic blood pressure (BP) reactivity. There were no significant correlations between a measure of the experience of anger-hostility and cardiovascular reactivity. The two types of anger-hostility were also found to relate differentially to life-style variables that have been identified as risk factors for coronary heart disease (CHD), with only the expression of anger-hostility showing positive relationships with these life-style CHD risk factors. These findings are discussed within the context of a similar differential relationship between the two dimensions of anger-hostility and CAD and CHD. Finally, significant negative relationships were obtained between the experience of anger-hostility and resting BP and heart rate levels. These findings are discussed within the context of other data suggesting that trait anxiety-neuroticism may have protective properties.
Both H2O2 (IC50 = 70 microM) and HOCl (IC50 = 8.5 microM) inhibited mitogen-induced MNL proliferation in a dose-dependent manner. This was found to be due to a depletion of intracellular ATP by at least two distinct mechanisms. HOCl and high concentrations (greater than 100 microM) of H2O2 inhibit ATP generation via sulfhydryl group oxidation on the active site of the glyceraldehyde-3-phosphate dehydrogenase (G3PDH) enzyme of the glycolytic pathway. On the other hand, low H2O2 concentrations cause ATP depletion by an activation of the DNA repair enzyme, poly(ADP-ribose)polymerase (pADPRP), leading to consumption of NAD+, an essential cofactor for G3PDH. The anti-oxidants ascorbate and cysteine protected MNL against the anti-proliferative effects of HOCl. Similar results were achieved with the HOCl-mediated inhibition of ATP production and G3PDH activity. However, ascorbate was unable to protect against H2O2-mediated inhibition of MNL functions, while cysteine protected against the inhibitory effects on ATP production and G3PDH activity, induced by this oxidant.
In this study the formation of DNA single-strand breaks in MNL in close proximity to activated phagocytes, or in contact with added H2O2 and/or HOCl, were evaluated. Neutrophils activated by phorbol myristate acetate (PMA), induced DNA-strand breaks in neighboring lymphocytes which increased after 1-2 h incubation in a repair medium. These DNA-strand breaks could be prevented by the addition of catalase or substitution of the neutrophils with cells from a patient with chronic granulomatous disease. Inclusion of the myeloperoxidase (MPO) inhibitor, sodium azide (NaN3), to the system was associated with less damage after 1-2 h incubation and a faster repair rate. Exposure of MNL to added reagent H2O2 (12-100 microM) was also accompanied by DNA damage. Addition of reagent HOCl (3-25 microM) did not induce any DNA-strand breaks. However, when combined with H2O2 (12.5 microM), HOCl increased H2O2-mediated DNA damage and compromised the repair process. Interactions between the phagocyte-derived reactive oxidants H2O2 and HOCl are probably involved in the etiology of inflammation-related cancer.
Primary malignant melanoma of the cervix was diagnosed in a patient presenting with postmenopausal bleeding. A cervical lesion was biopsied, and diagnosis was established by electron microscopy and staining procedures. After failing radiotherapy, the patient was treated with simple hysterectomy and bilateral salpingo-oophorectomy. The cytology, histology, and electron microscopy of this lesion are presented in addition to a clinical discussion.
We conducted a survey of a random sample of California orthodontists and of general dentists to compare their infection control procedures. Questionnaires were returned by 124 orthodontists (56% response rate) and 126 general dentists (61% response rate). Eighteen questions were asked covering practice profile, perception of risk from hepatitis B virus (HBV) and human immunodeficiency virus (HIV), exposure to blood, barrier protection used, and sterilization and disinfection procedures. Gloves always were worn by 80% of the orthodontists sampled, 63% always wore glasses, and 59% changed gloves between patients. Orthodontists sterilized their instruments 66% of the time and pliers 49% of the time. Compared with general dentists, orthodontists' perception of risk, use of barrier protection, and sterilization and disinfection procedures were lower in all areas. Our data suggest that poorer performance may be because orthodontists: (1) perceive their younger population of patients at less risk for HBV and HIV; (2) treat 2.5 times as many patients, which increases the costs of infection control; (3) do not use invasive procedures; and (4) perceive that glove use decreases dexterity. Orthodontists should follow the American Dental Association/Council on Dental Therapeutics infection control guidelines for universal precautions. To meet these guidelines, orthodontists still need improvement in all aspects of their infection control procedures.
Diastolic filling of the left ventricle, as assessed by transesophageal pulsed Doppler echocardiography during and in the early phase following coronary artery bypass grafting, was investigated in nine patients without valvular disease or left ventricular hypertrophy. The ratio between the maximal heights of the early diastolic flow-velocity peak and the late (atrial) diastolic flow-velocity peak, the E:A ratio, and also the deceleration time of the early peak were calculated as indices of left ventricular filling. The E:A ratio decreased from 1.01 +/- 0.06 after induction of anesthesia to 0.46 +/- 0.06 on arrival in the intensive care unit (ICU). The E:A ratio then increased and reached 0.87 +/- 0.08 after 6 hours in the ICU. This increase in E:A ratio in the ICU was due to an increasing peak velocity of the E wave. The deceleration time decreased after surgery and increased from 111 +/- 25 to 145 +/- 12 milliseconds in the ICU. Pulsed Doppler indices of diastolic filling are known to be altered by changes in hemodynamic parameters, to be load-dependent, and to vary with heart rate. In the ICU, pulmonary capillary wedge pressure remained unchanged, heart rate decreased by approximately 12%, and systemic vascular resistance decreased by approximately 40%. The changes in hemodynamic parameters could have affected the E:A ratio, but it is unlikely that they could explain the marked increase in the E:A ratio that occurred in the ICU. The results, therefore, imply the presence of impaired diastolic filling immediately after cardiopulmonary bypass with gradual, but not complete, recovery during the first 6 hours in the ICU.
OBJECTIVES: Describe an outbreak of surgical wound infections associated with total hip arthroplasty; identify risk factors for surgical wound infection during the pre-outbreak and outbreak periods. SETTING: A 100-bed hospital. From May 1 to September 30, 1988, 7 of 15 patients who underwent total hip arthroplasty developed surgical wound infections from Staphylococcus aureus (5), Enterobacter cloacae (1), beta-hemolytic streptococci (1), enterococci (1), coagulase-negative staphylococci (1), and Escherichia coli (1) (attack rate = 46.7%). DESIGN: Retrospective cohort studies comparing surgical wound infection rates by patient- and procedure-related risk factors during the pre-outbreak and outbreak periods were conducted. Drop plate quantitative air culturing was conducted in 10 consecutive total hip arthroplasties in the subsequent 6 months. RESULTS: Rates of surgical wound infection were surgically higher for arthroplasties in which no intraoperative prophylactic antimicrobials were given (44% versus 8%, relative risk [RR] = 5.4, p = .01), or in which the posterior approach (20% versus 3%, RR = 6.7, p = .04) or a specific prosthesis (39% versus 5%, RR = 6.3, p = 0.01) was used. The surgical wound infection rate was highest when one circulating nurse, Nurse A, assisted (47% versus 4%, RR = 12.8, p less than .001). Logistic regression analysis identified use of the posterior approach (RR = 1.8, p = .04) and Nurse A's participation (RR = 5.0, p less than .001) as independent risk factors for surgical wound infection. Interviews of the nursing supervisor indicated that Nurse A had recurrent dermatitis on her hands. During 6 months following Nurse A's reassignment, the rate declined significantly (from 7/15 to 0/10, p = .01). Drop plate culturing yielded 2 to 10 colonies per plate of organisms that did not match outbreak organisms. CONCLUSIONS: Outbreaks associated with personnel generally involve only 1 species. In this outbreak, Nurse A (possibly because of her dermatitis), technique, the posterior approach, and/or other undetermined factors were the primary predictors of surgical wound infection.
To explore the feasibility of preparing a human immune globulin specific for respiratory syncytial virus (RSV) by screening plasma donors, the ability of seven RSV antibody assays to identify plasma-yielding IgG with high virus-neutralizing and animal-protective activities was compared. IgG prepared from plasma units selected by microneutralization assay had significantly higher activity in protecting mice from respiratory RSV challenge than did IgGs prepared from plasmas selected by three direct ELISAs using purified F protein, G protein, or RSV-infected cell lysate, by two competitive ELISAs with RSV neutralizing monoclonal antibodies directed to the F2 or F3 epitopes of the F protein, or by plaque reduction neutralization. Relative to IgG made from unselected plasma, microneutralization-screened IgG was enriched fivefold by plaque-reduction neutralization assays done with or without complement. The microneutralization assay identified RSV antibodies with highest animal protective activity. This assay will be useful for identifying plasma donors for the preparation of a human immune globulin with high protective activity against RSV and deserves further evaluation for prediction of protective antibody concentrations in children.
The in vitro effects of the Pseudomonas aeruginosa-derived phenazine pigments pyocyanin and 1-hydroxyphenazine (1-hp) on neutrophil elastase release and myeloperoxidase-induced inactivation of alpha-1-protease inhibitor (alpha 1-PI) were investigated. 1-hp (6-25 microM), but not pyocyanin, caused a dose-dependent enhancement of elastase release by FMLP:cytochalasin B (CB)-activated human neutrophils. 1-hp (0.78-6.25 microM) also increased the oxidative inactivation of the elastase inhibitory capacity of alpha 1-PI exposed to FMLP:CB-activated neutrophils. Methionine, a scavenger of hypochlorous acid, completely protected alpha 1-PI from inactivation by stimulated neutrophils in the presence or absence of 1-hp. Similar protective effects were observed with sodium azide, an inhibitor of myeloperoxidase. P. aeruginosa-derived 1-hp may promote an elastase-antielastase imbalance in vivo by increasing the release of neutrophil elastase and by enhancing the oxidative inactivation of alpha 1-PI, thereby contributing to the development of tissue destruction in P. aeruginosa-infected patients.
The cellular uptake by human neutrophils and the intraphagocytic biological activity of the new macrolide antimicrobial agent dirithromycin (0.01-2 mg/L) compared with erythromycin was investigated in vitro. Staphylococcus aureus, Listeria monocytogenes and Legionella pneumophila were used as the test intracellular microbial pathogens. After coincubation (45 min at 37 degrees C) of neutrophils with a fixed concentration of 2 mg/L of each antibiotic the respective intracellular/extracellular ratios for erythromycin and dirithromycin were 6.1 +/- 2.5 and 10.6 +/- 2 respectively (P < 0.005). Using a combination of techniques (colony counting, radiometry and fluorescence microscopy) both erythromycin and dirithromycin at concentrations of 0.01 and 0.5 mg/L and higher, respectively, were found to possess dose-related intraphagocytic bacteristatic activity for each of the test microbial pathogens. The effects of dirithromycin and erythromycin (1-20 mg/L) on neutrophil chemotaxis and generation of reactive oxidants by these cells were also investigated in vitro. Both antimicrobial agents caused a dose-related stimulation of neutrophil migration which was associated with inhibition of leucoattractant-activated generation of superoxide and activity of the myeloperoxidase/H2O2/halide system. However, superoxide generation by neutrophils activited with opsonized zymosan or phorbol myristate acetate was unaffected by the macrolides. These findings demonstrate that dirithromycin accumulates in human neutrophils, is biologically active intracellularly and modulates leucoattractant-activated superoxide generation and chemotaxis.
OBJECTIVE: To assess the presence of covert HIV-1 infection. SETTING: High-risk seronegative homosexual men from the Pittsburgh portion of the Multicenter AIDS Cohort Study were examined for the presence of HIV-1 infection. PATIENTS, PARTICIPANTS: Ten men (group 1) were examined prospectively for the presence of HIV-1 in their freshly-obtained peripheral blood mononuclear cells (PBMC). Furthermore, cryopreserved PBMC from 26 men (group 2) at their first visit (1984-1985) were examined retrospectively for the presence of HIV-1. MAIN OUTCOME MEASURES: PBMC samples from groups 1 and 2 were examined for HIV-1 by polymerase chain reaction (PCR) using gag, env and strong-stop (long terminal repeat) specific primers. In addition, fresh PBMC samples from group 1 were examined for HIV-1 by virus culture. RESULTS: None of the 10 PBMC samples from group 1 were positive for virus culture and PCR. Only one of the 26 men from group 2 was positive for gag and strong-stop DNA sequences. This PCR-positive, seronegative subject was found to be negative for HIV-1 by PCR at follow-up visits up to 48 months later. None of 15 seronegative, low-risk homosexual men and 12 seronegative heterosexual men were found to be PCR-positive for HIV-1. However, six HIV-1-seropositive men were positive by PCR for gag, env, and strong-stop HIV-1 DNA sequences. CONCLUSIONS: These results suggest a low prevalence of covert HIV-1 infection in high-risk seronegative homosexual men in our geographic area.
A stratified random sample of 195 subjects was selected from the membership of an urban transit union in California, two thirds consisting of motor coach operators and one third serving as a nondriving comparison group. Based on an orthopaedic medical history and physical examination, 80.5% of drivers were found to be experiencing back or neck pain at the time of examination, in contrast with 50.7 percent of nondrivers, itself a sizable percentage. For both groups, most pain was mild, (53.9 and 29.9%, respectively). The amount of severe pain was essentially the same in the two groups (10.2% and 9.0%). Both groups were most subject to low back pain. Drivers were most distinctive for movement-related pain in the cervical spine. They were also more subject in any part of the spine to postural pain. The latter finding suggests the need to introduce ergonomic and scheduling changes in the work of operating a motor coach. Drivers more than nondrivers struggled against their pain by doing exercise, seeking professional treatment, and taking medications, indicating that spinal disorders constitute a prominent health concern for workers in this occupation.