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Biomedical subjects

L A Thomas

Publications and source records attributed to L A Thomas.

At least 19 recordsLinked to original sources

Contact stimulation of cell migration.

Mass migrations of dense cell populations occur periodically during embryonic development. It is known that extracellular matrices, through which the cells migrate, facilitate locomotion. However, this does not explain how cells, such as neural crest, can migrate as a dense cohort of cells in essentially continuous contact with one another. We report here that unique behavioral characteristics of the migrating cells may contribute to cohesive migration. We used time-lapse video microscopy to analyze the migration of quail neural crest cells and of two crest derivatives, human melanoma cells and melanocytes. These cells migrated poorly, if at all, when isolated, but could be stimulated up to 200-fold to travel following contact with migrating cells. This phenomenon, which we have termed "contact-stimulated migration," appeared to activate and sustain migration of the mass of cells. Cells that became dissociated from the others ceased directional migration, thereby limiting aberrant cell dispersion. Fibroblasts were minimally responsive to this novel phenomenon, which may be crucial for major, mass cell migrations.

Animals

Relationship between colloid osmotic pressure and plasma protein concentration in cattle, horses, dogs, and cats.

The relationship between colloid osmotic pressure (COP) and protein concentration was investigated for purified proteins and plasma samples obtained from cattle, horses, dogs, and cats. At equivalent concentrations, bovine albumin exerted a COP that exceeded that of gamma-globulins by a mean factor of 4.4. Similar relationships between COP and protein were observed in the other species. Consequently, for a given total protein concentration, COP was dependent on the albumin/gamma-globulins ratio. A commonly used nomogram for estimating COP from protein concentration, the Landis-Pappenheimer equation, did not provide reliable results for plasma samples from these species.

Animals

Intraluminal radiation therapy per endoprosthesis: a case study.

Palliation of cholangeocarcinomas has been achieved by radiation delivered to the bile duct via endoprothesis. This case study supports and extends the works of others by describing the endoscopic techniques involved in the implantation of iridium seeds within a nasobiliary catheter. The case presented demonstrates endoscopic radiation treatment with no systemic radiation effects in a patient whose life extension was 19 months.

Adenocarcinoma

Atrial automatic tachycardia-reversion pacemakers: their economic viability and impact on quality-of-life.

UNLABELLED: Refractory supraventricular tachyarrhythmias may be both difficult and costly to control medically and can interfere with the patient's lifestyle. Newer treatment modalities are available for their management, and these require comprehensive assessment. We therefore compared costs and selective indices of patient benefit in a group of 17 patients in whom an atrial antitachycardia (Intermedics Intertach 262-12) pacemaker was placed for refractory supraventricular tachyarrhythmias. Prior medical therapy was compared to subsequent automatic antitachycardia pacemaker treatment. The total medical costs (admissions, emergency room visits, office visits, and medication costs) and the number of hospitalizations and medications were compared prior to implantation (F/U 69.3 +/- 61 months) and after implantation (F/U 15.3 +/- 7.8 months). A detailed quality-of-life questionnaire was also obtained 36.6 +/- 11 months after implantation. RESULTS: There were significant per patient differences in total cost before and after implantation: monthly costs were $505 +/- $833 before pacemaker implantation and $105 +/- $117 monthly afterward (P less than 0.005). Pacemaker implantation hospitalization costs were $19,063 +/- $8,362. Monthly medication costs averaged $46 before versus $15 after implantation (P less than 0.01). The number of medication types also differed with an average 5.5 medication types per patient before versus 1.2 after implantation (P less than 0.001). There were 8.6 yearly hospital admissions in the whole group before implantation, versus 4.7 admissions in the group per year thereafter. Patients demonstrated significant improvement in 80% of the quality-of-life parameters studied. CONCLUSION: Adjunctive atrial automatic tachycardia-reversion pacemaker therapy may be cost-competitive over time when compared to medical therapy alone in patients with refractory supraventricular tachyarrhythmias and appears to improve overall quality-of-life.

Costs and Cost Analysis

The influence of endocardial electrode fixation status on acute and chronic atrial stimulation threshold and atrial endocardial electrogram amplitude.

UNLABELLED: The endocardial atrial electrogram or "P wave amplitude" (PWA) and pacemaker atrial stimulation thresholds are important parameters determining correct pacing system function. Pacemaker lead fixation mechanism and lead age may negatively influence these parameters. Therefore, we compared acute and chronic PWA and atrial stimulation thresholds in 33 patients with permanent transvenous atrial screw-in leads, follow-up 647 days +/- 297 days; and in 31 patients with nonscrew leads, follow-up 855 days +/- 512 days (P = ns). RESULTS: The PWA differed between the two lead types acutely (1.97 mV +/- 0.8 mV for screw-in versus 2.48 mV +/- 1.1 mV for nonscrew-in leads; P less than 0.05), but not chronically (2.21 mV +/- 0.8 mV vs 2.2 mV +/- 1.2 mV; P = ns). Acute and chronic atrial pacing thresholds did not differ between groups. We also analyzed an early interim PWA in a subgroup of patients (mean 31 days after implantation). The nonscrew fixation group interim PWA was 1.76 mV +/- 0.9 mV versus 2.7 mV +/- 1.2 mV at implant (P less than 0.001). The screw-in lead interim PWA was 2.04 mV +/- 0.9 mV versus 1.97 mV +/- 0.7 mV at implant (P = ns). CONCLUSIONS: (1) A significantly higher endocardial PWA occurs at the time of lead implantation in nonscrew versus screw-in lead groups, but the chronic PWA does not differ between the two groups. (2) A transient but marked early (mean approximately 31 days) attenuation of the PWA occurs only with nonscrew-in leads. (3) Atrial threshold stimulation energies do not differ between the two lead groups acutely or during follow-up.

Aged

Variation in P wave amplitude immediately after pacemaker implantation: possible mechanism and implications for early programming.

The P wave amplitude (PWA) plays an important role in determining atrial sensing capabilities. To assess early PWA change, we compared the unipolar PWA in 43 patients at the time of atrial lead placement, measured by a pacing systems analyzer, to the unipolar PWA recorded at the end of pacemaker surgery, from telemetered atrial endocardial electrograms. Individual PWA varied from a decrease of 5.2 mV to an increase of 2 mV (-63% to 267%). In 33 patients with active fixation leads, the implant PWA was 1.96 +/- 0.99 mV versus 2.4 +/- 1.4 mV after surgery. In 11 patients with passive fixation leads, the implant PWA was 2.8 +/- 1.9 mV versus 1.9 +/- 0.8 mV after surgery. The PWA change, measured as the difference between the postsurgical and implant PWA was 0.43 +/- 0.8 mV in active versus -0.86 +/- 1.6 mV in the passive fixation lead groups (P less than 0.05). Considerable change in individual P wave amplitude can therefore occur very early after pacemaker implantation. The direction differs significantly between active (predominantly positive) and passive fixation groups (predominantly negative). These data suggest that an adequate margin of safety is important when initially programming atrial sensitivity, particularly when using passive fixation leads.

Aged

Autonomic responses in chest pain syndromes as compared to normal subjects.

The heart rate response to standing, cough, hand grip, and deep breathing were examined in normal subjects and coronary artery disease patients (greater than 70% diameter narrowing). The heart rate responses to these maneuvers were reduced in coronary patients and in anginal patients with normal coronary angiograms, as compared to normals. Detection (with the heart rate response to standing) was determined by using an RR interval cutoff of 140 ms for males and 120 ms for females discriminated between normals and CAD patients. In men sensitivity was 0.58, specificity 0.87 and CCR 0.75, and in women sensitivity was 0.67, specificity 0.79 and CCR 0.75. These values are similar to those reported for ST segment depression in similar populations. When separating normals from those with 2 and 3 vessel disease--sensitivity is 0.67, specificity 0.87, predictive value 0.71 and CCR 0.80. The response to cough, hand grip, and deep breathing showed similar trends but had less specificity than the response to standing. Thus, the heart rate response to most autonomic maneuvers is blunted in subjects with coronary disease and in those with pain syndromes sent for coronary angiography. These findings need testing in larger populations but autonomic maneuvers fail to discriminate patients with coronary disease from those with normal angiograms presenting with chest pain syndromes.

Adult

The role of prostaglandins E and F in acalculous gallbladder disease.

Prostaglandins have been postulated to be involved in the formation of gallstones and the pain and inflammation of calculous gallbladder disease. This report evaluated prostaglandin E and F levels in patients with acalculous gallbladder disease. Control gallbladders were obtained from patients undergoing cholecystectomy during insertion of hepatic artery catheters for regional, hepatic chemotherapy. Patients without gallstones and with long-standing post-prandial biliary colic with abnormal cholecystokinin administration underwent cholecystectomy for chronic acalculous cholecystitis. A third group of patients underwent cholecystectomy for acute acalculous cholecystitis. Gallbladder mucosa and muscle were separated, and prostaglandin E and F concentrations in mucosal and muscle or mucosa were identified in gallbladders from patients with chronic acalculous cholecystitis compared to gallbladders from patients without biliary tract symptoms. In gallbladders from patients with acute acalculous cholecystitis a seven-fold increase in PGE production by muscle tissue and mucosal cells was found. The more histologically inflamed gallbladders had higher mucosal and muscle prostaglandin E concentrations than were found in less inflamed gallbladders. Prostaglandin F levels were not significantly changed or were decreased, resulting in a significant increase in the ratio of PGE/PGF in acutely diseased gallbladders when compared to normal gallbladders. Prostaglandin E may be a manipulatable intermediary in the sequence of events that results in the development of acute acalculous cholecystitis.

Acute Disease

Genetic regulation of light damage to photoreceptors.

Albino mice of different inbred strains have been exposed to constant fluorescent lighting at an illuminance level of 115-130 ft-c for intervals of 1-6 weeks. Under these conditions the photoreceptors in retinas of albino BALB/cByJ mice rapidly degenerate, whereas the photoreceptors in retinas of albino C57BL/6J-c2J mice are remarkably more resistant to light damage. F1 heterozygotes produced from these two strains display an intermediate degree of light-induced degeneration. These findings demonstrate that phenotypically identical populations with different genetic constitutions can show markedly different sensitivities to light, and that genetic factors must now be included as a determinant for the severity of light damage.

Animals

Identification of phase-specific antigenic fractions of Coxiella burnetti by enzyme-linked immunosorbent assay.

Antigenic fractions of Coxiella burnetii phase variants were identified with an enzyme-linked immunosorbent assay (ELISA). Immune sera from guinea pigs immunized with Formalin-inactivated phase I or phase II whole cells were used to measure the antigenic activity of whole cells and various soluble and particulate preparations. Phase-specific antigens of C. burnetii whole cells and fractions were compared by dose-response curves at different (antigen and antibody) dilutions. Water-soluble extracts prepared by meta-periodate, ether, and phenol extraction of phase I whole cells yielded antigenic fractions which reacted with anti-phase I antibodies. The extraction of phase I whole cells with dimethyl sulfoxide, trichloracetic acid, and Formalin yielded antigenic fractions which detected antibodies in both anti-phase I and -phase II sera. Interestingly, the trichloracetic acid extract of phase I whole cells also contained a component which bound nonimmune immunoglobulin. The sera of animals immunized with whole cells of the phase II Australian QD strain reacted with lipopolysaccharides of the phase I and phase II Nine Mile strains. Therefore, variations in lipopolysaccharide structure among phase variants of C. burnetii were detected as cross-reactions with immune sera from an interspecific strain. Comparisons of immunofluorescence, microagglutination, and the complement fixation assays with the ELISA indicated greater sensitivity and specificity of the ELISA for the measurement of phase-specific antigens and antibodies.

Animals

Humoral immune response to Q fever: enzyme-linked immunosorbent assay antibody response to Coxiella burnetii in experimentally infected guinea pigs.

The response of guinea pigs experimentally infected with Coxiella burnetii organisms, the etiologic agents of Q fever, was obtained by the measurement of fever, circulating infectious C. burnetii cells, and anti-C. burnetii antibodies. The detection of antibodies by the enzyme-linked immunosorbent assay (ELISA) and traditional methods against phase I whole cells, phase II whole cells, and phase I lipopolysaccharide (LPS-I) (a virulence marker for phase I cells) antigens in the serum samples of infected animals revealed marked differences between intrastrain phase variants. Animals infected with the phase I Nine Mile strain produced a concomitant increase in temperature, circulating infectious C. burnetii cells, and antibodies against phase II cells, phase I cells, and LPS-I. At 15 weeks, a challenge of phase I-infected animals with viable phase I cells resulted in anamnestic antibody responses to phase I cells and LPS-I but not to phase II cells. Infection of animals with the phase II Nine Mile strain produced antibodies against only phase II cells. The challenge of phase II-infected animals at 15 weeks with viable phase II cells resulted in anamnestic antibody responses to phase I and phase II cells but not to LPS-I. Suppression of anti-phase II responses by the phase I challenge was apparent with only the ELISA, because the immunofluorescence, microagglutination, and complement fixation assays were insensitive to these changes. The sensitivity and specificity of the ELISA with whole-cell and the LPS-I antigens in the detection of phase-specific antibody revealed that avirulent phase II cells induced an immune response to phase I antigenic epitopes. Although the avirulent phase II cells were rapidly cleared by the host immune responses, they were sufficiently infective to induce antibody responses to both phase variants. Thus, in the occurrence of Q fever, any conventional serological technique that uses only phase II antigens may not provide a true incidence of naturally acquired infection with both phase I and II C. burnetii organisms.

Agglutination Tests

Characterization of monoclonal antibodies protecting mice against Rickettsia rickettsii.

Hybridomas producing monoclonal antibodies to Rickettsia rickettsii were prepared from mice to investigate the function of rickettsial antigens. Of the 31 reactive hybridoma lines thus far tested for immunoglobulin subclasses, 11 belonged to the IgG2A subclass, 9 to the IgG2B subclass, and 7 to the IgG3 subclass; four did not react with any of the isotyping sera. Five of the antibodies recognized epitopes present on molecules that were presumed to be polysaccharide and heterogeneous in molecular weight. Twenty monoclonal antibodies reacted with a 170,000-dalton antigen, and six precipitated both the 133,000- and 32,000-dalton polypeptides. Only those antibodies to the 170,000- and 133,000-dalton antigens protected mice from challenge with R. rickettsii. Antibodies to these same antigens were detected in sera from patients convalescing from Rocky Mountain spotted fever. All monoclonal antibodies reacted with antigens apparently located on the rickettsial surface. The protective activity of these antibodies was not correlated with their reactivity in complement fixation, enzyme-linked immunosorbent assay, and immunofluorescence tests.

Animals

The role of prostaglandins in feline experimental cholecystitis.

The arachidonic acid metabolites are recognized as important biochemical mediators of inflammation in a wide variety of disease processes. Also the ability to change prostaglandin formation by inhibition of prostaglandin synthetase activity with aspirin and other nonsteroidal anti-inflammatory agents is important in the treatment of many diseases with an inflammatory component. Although gallbladder disease is primarily related to the development of cholesterol stones, inflammation is an important contributor to the subsequent symptoms and accompanying illness. This research evaluates the formation of prostaglandins E and F by gallbladder tissue. Gallbladder mucosal cells and muscle tissue were maintained in tissue culture medium. Production of prostaglandins E and F was determined by quantitation by radioimmunoassay of these substances in culture media and mucosal cell and muscle tissue homogenates. Prostaglandin production by normal gallbladder tissue in a variety of species including man was consistently demonstrated in the nanogram per milligram mucosal cell or muscle tissue protein range. In cats, inflammation was produced by placing a 4% carrageenan-soaked sponge in the gallbladder, and prostaglandin synthetase inhibition was produced by indomethacin administration. The feline gallbladder increased prostaglandin F production in inflamed gallbladder mucosal cells and E production by inflamed gallbladder muscle tissue, and indomethacin inhibited these increases. A positive, significant correlation existed between the increased prostaglandin E and prostaglandin F production by inflamed gallbladder tissue and the amount of inflammation present as determined by a histologic score. The histologic score of the amount of gallbladder inflammation present was decreased significantly by indomethacin when compared with inflamed gallbladders from cats not receiving indomethacin. Prostaglandins may play a role in the inflammatory processes occurring in acute cholecystitis.

Animals

Indirect hemagglutination test for detection of antibody to Rickettsia rickettsii in sera from humans and common laboratory animals.

Antibody production in humans and three species of laboratory animals infected with Rickettsia rickettsii was determined with the indirect hemagglutination test. Rabbits, guinea pigs, and mice were inoculated with R. rickettsii and bled at intervals. Antibody which agglutinated both fresh and glutaraldehyde-fixed sheep erythrocytes sensitized with antigen prepared either from purified rickettsiae or from infected yolk sacs was found in rabbit sera at all intervals tested (10 to 59 days postinfection). Antibody which agglutinated fresh but not glutaraldehyde-fixed erythrocytes sensitized with either of the above antigens was detected in guinea pig sera obtained 7, 14, and 28 days postinfection. Antibody was found in mice inoculated with 5.6 x 10(6) plaque-forming units of R. rickettsii but not in mice given 5.6 x 10(2) plaque-forming units. Peak indirect hemagglutination titers occurred in nonvaccinated human Rocky Mountain spotted fever patients about 3 weeks after onset of illness, and antibody was still detectable after 1 year. Both human immunoglobulin G and human immunoglobulin M antibodies agglutinated sensitized cells, but immunoglobulin M antibodies apparently were more efficient. The indirect hemagglutination test is useful for the titration of human, rabbit, guinea pig, and mouse antibodies when the appropriate erythrocytes are used.

Animals

A comparison of serologic methods for diagnosis of Rocky Mountain spotted fever.

Sera referred to the North Carolina Division of Health Services for rickettsial serology in 1974 were tested by complement fixation (CF), microimmunofluorescence (micro-IF), microagglutination (MA) and hemagglutination (HA) for antibodies against Rickettsia rickettsii. There was good agreement among micro-IF,MA and HA tests in detecting antibody responses to this agent, but the CF test was definitely less sensitive than the others, even in illnesses with classical clinical manifestations of Rocky Mountain spotted fever (RMSF). Some variables that seemed to influence the CF result were the slow rate of increase in antibody titers, timing of serum collection, early antibiotic treatment and possibly, the particular association of CF antibody response with the IgG immunoliobulin class. Greater use of these newer, but relatively untried, serodiagnostic procedures is recommended infuture studies of RMSF.

Agglutination Tests

Sunday Canyon virus, a new ungrouped agent from the tick Argas (A.) cooleyi in Texas.

A new arbovirus was isolated from Texas, U.S.A., populations of the Cliff Swallow parasits Argas (Argas) cooleyi Kohls and Hoogstraal, 1960. The virus, named Sunday Canyon, is serological urelated to any of 185 arbovirus strains or 20 other viral agents with which it was compared. Morphologically it resembles Bunyamwera viruses and, in common with them, is sensitive to lipid solvents and acid pH, and apparently possesses RNA. Although considerably resistant to a temperature of 41.5 degrees C, it rapidly loses infectivity when incubated at 56 degrees C. It is lethal for newborn white mice and infective for the Vero and Antheraea eucalypti cell lines. Sundays Canyon virus is the second tick-associated, Bunyamwera virus-like agent known from North America and the third virus to be reported from A. cooleyi in Texas.

Animals