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Biomedical subjects

J Thompson

Publications and source records attributed to J Thompson.

At least 307 records · Page 17Linked to original sources
PubMed1996

Recombinant baculovirus influenza A hemagglutinin vaccines are well tolerated and immunogenic in healthy adults.

In a prospective double-blind trial, the reactogenicity and immunogenicity of recombinant baculovirus influenza A vaccines containing purified full-length hemagglutinin (HA) were compared with standard trivalent inactivated vaccine (TIV). The recombinant baculovirus influenza A vaccines (rHA0) were monovalent (containing 45 micrograms of A/Beijing/92[H3] and 15, 45, and 135 micrograms of A/Texas/91[H1]) and bivalent (containing 45 micrograms of both A/Beijing/92 and A/Texas/91). The bivalent rHA0 vaccine produced fewer local side effects than the TIV (50% vs. 88%, P = .003). The hemagglutinin inhibition (HAI) responses (defined as a > or = 4 increase in HAI) to A/Beijing rHA0 in the monovalent A/Beijing/92, the bivalent vaccine, and the TIV were 68%, 76%, and 46%, respectively (P = .086). Increasing doses of A/Texas rHA0 (15 micrograms [60%], 45 micrograms [69%], and 135 micrograms [76%]) and bivalent HA (76%) gave better immunologic responses to H1 than did TIV (31%; P = .003).

Adolescent↗
PubMed1996

Role of phagocytosis in activation of the coagulation system in Streptococcus sanguis endocarditis.

The formation of vegetations consisting of fibrin, cellular elements, humoral factors, and bacteria is the central event in the pathogenesis of bacterial endocarditis. Fibrin formation occurs on the vegetation, the coagulation system being activated locally via the expression of tissue factor (TF) on fibrin-adherent monocytes. This study was performed to assess the importance of phagocytosis of fibrin-adherent Streptococcus sanguis in the stimulation of TF expression on fibrin-adherent monocytes, as well as a role for "frustrated" phagocytosis. With the latter process, these cells are unable to remove bacteria from the fibrin surface but nonetheless might be activated to generate TF. We found that serum was not required for the stimulation of TF expression by fibrin-adherent monocytes in the presence of S. sanguis in an in vitro model for bacterial endocarditis. The bacterial adhesin dextran did not influence the TF activity (TFA) of fibrin-adherent monocytes: TFA was the same after stimulation with a dextran-positive streptococcus as with its dextran-negative mutant. Furthermore, dextran did not influence the TFA of endocardial vegetations, which was the same for vegetations isolated from rabbits infected either with dextran-positive S. sanguis or its dextran-negative mutant. These results do not support the hypothesis that in bacterial endocarditis (frustrated) phagocytosis significantly contributes to TF expression on vegetation-adherent monocytes. Fibronectin, however, although not influencing the fibrin binding of the streptococci, did enhance the TFA of monocytes in a concentration-dependent manner. We conclude that although streptococci do enhance expression of TFA on monocytes, phagocytosis and bacterial adhesins do not play a major role in this process. Stimulation of monocyte TFA may be more dependent on interactions between monocytes and the vegetational surface via fibronectin receptors, such as VLA 4 and VLA 5 (very late antigens 4 and 5).

Animals↗
PubMed1996

Influence of monocytes and antibiotic treatment on tissue factor activity of endocardial vegetations in rabbits infected with Streptococcus sanguis.

A main feature in the pathogenesis of bacterial endocarditis is the activation of the coagulation system via the extrinsic pathway, resulting in the formation of infected endocardial vegetations. Earlier studies gave indirect evidence that monocytes play an important role in the procoagulant response during the course of the disease. In this study, we assessed the role of monocytes more directly. We compared weights and tissue factor activities (TFA) of endocardial vegetations of normal rabbits infected with Streptococcus sanguis with those of rabbits which were treated with the cytostatic drug etoposide (Vepesid; Bristol-Myers Squibb B.V.) to induce a selective monocytopenia. Furthermore, the importance of the presence of bacteria was determined through the influence of antibiotic treatment on TFA, vegetational weight, and infection of the vegetations. The TFA of the vegetations was measured chromogenically by monitoring the factor VII-dependent activation of factor X with an amidolytic assay for factor Xa. We found that the degree of infection and the weight of vegetations of rabbits treated with the cytostatic drug etoposide did not differ from that of untreated rabbits. Their TFA, however, was significantly lower than the TFA of vegetations of rabbits not treated with etoposide. We also found that, as with the monocytopenic rabbits, the weight of the vegetations was not reduced in penicillin G-treated rabbits. The degree of infection and TFA, however, were significantly lower. We conclude that monocytes indeed are involved in the activation of the coagulation system during the course of bacterial endocarditis and that the degree of infection is positively correlated to the TFA of the vegetations.

Animals↗
PubMed1996

Deletion of purE attenuates Brucella melitensis infection in mice.

We previously showed that a purE mutant (delta purE201) of Brucella melitensis 16M is attenuated for growth in cultured human monocytes (E. S. Drazek, H. H. Houng, R. M. Crawford, T. L. Hadfield, D. L. Hoover, and R. L. Warren, Infect. Immun. 63:3297-3301, 1995). To determine if this strain is attenuated in animals, we compared the growth of the delta purE201 mutant with that of strain 16M in BALB/c mice. The number of bacteria in the spleen and spleen weight peaked for both strains between 1 and 2 weeks postinfection (p.i.), though the number of delta purE201 cells was significantly less than the number of 16M cells recovered from the spleens of infected mice. During the next 6 weeks, delta purE201 was essentially eliminated from infected mice (three of five mice sterile; < 100 CFU in two of live mice at 8 weeks p.i.), whereas bacteria persisted at a high level in the spleens of 16M-infected mice (about 106 CFU per spleen). The number of bacteria in the livers and lungs of mice infected with either strain paralleled those in the spleen. Mice infected with 16M had a strong inflammatory response, developing dramatic and prolonged splenomegaly (five to eight times normal spleen weight) and producing serum interleukin-6. In contrast, mice infected with delta purE201 developed only mild, transient splenomegaly at 1 week p.i. and produced no interleukin-6 in their serum. We further characterized the host response to infection by measuring changes in immune spleen cell populations by flow cytometry. CD4- and CD8-positive lymphocytes declined by I week in both experimental groups, while MAC-1-positive cells increased. T-cell subpopulations remained low or declined further, and MAC-1 cells increased to three times normal levels during 8 weeks of infection with 16M but returned to normal by 4 weeks after infection with delta purE201. These results document infectivity and attenuation of delta purE201 and suggest that it should be further evaluated as a potential vaccine.

Animals↗
PubMed1996

The effect of sleep deprivation on sleep states, breathing events, peripheral chemoresponsiveness and arousal propensity in healthy 3 month old infants.

We wished to investigate the effects of sleep deprivation on sleep, arousal propensity, respiratory events and peripheral chemoresponses in healthy infants, since these effects might be relevant to mechanisms concerned with some cases of sudden infant death syndrome. Paired observations were made overnight during natural sleep and following sleep deprivation, in a randomized fashion, in 15 healthy infants aged 78 (7) days (mean (SD)). Polysomnograms were recorded and sleep was scored using Anders' criteria. Respiratory events were categorized into central, mixed and obstructive apnoeas. Peripheral chemoresponses were measured during quiet sleep from the respiratory response to two-breath alternations in fractional inspiratory oxygen (F1, O2) (0.42 and 0.00). Arousal propensity was determined from awakening and arousal thresholds to graded photic and auditory stimuli during quiet sleep, and from spontaneous awakenings and limb movements. Compared with natural sleep, following sleep deprivation infants maintained a greater proportion of quiet sleep (39 vs 44%). There was no measurable change in arousal propensity. During quiet sleep, obstructed breathing events tended to be more common after sleep deprivation (0.1 vs 0 events.h-1) and the expiratory time during baseline breathing increased significantly (1.27 vs 1.58 s) although the decrease in respiratory rate was not significant (32 vs 30 breaths.min-1). Peripheral chemoresponses altered significantly, alternations in tidal volume/inspiratory time (VT/tI) as a measure of inspiratory drive increased after sleep deprivation (9 vs 21%). In conclusion, following short-term sleep deprivation in infancy, respiratory control alters, peripheral chemoresponsiveness increases in magnitude and the timing of baseline breathing alters, without any detectable alteration in arousal propensity. This state may be associated with an increased vulnerability to obstructive respiratory events.

Arousal↗
PubMed1996

Peripheral chemoresponses of infants measured by a minimally invasive method utilizing two-breath alternations in Fl,02.

The aim of this study was to develop a minimally invasive and reliable method for measuring peripheral chemoresponsiveness to oxygen in infants, and to establish baseline data from normal infants at 12 weeks of age. Two-breath alternations in fractional inspired oxygen (FI,O2), switching between 0.42 to 0.00 were given for 2 min periods via a face mask (held close to the face but without contact) to 18 healthy infants during quiet sleep. End-tidal oxygen concentrations alternated between 21 and 11%. Instantaneous minute ventilation (V'E) and its components tidal volume (VT), respiratory frequency (fR) inspiratory and expiratory times (tI and tE), inspiratory flow (VT/tT), and inspiratory duty cycle (tI/ttot) were measured by respiratory inductance plethysmography. Two-breath alternations in each of the ventilatory components were matched with the corresponding alternating end-tidal oxygen record and compared with contiguous pre- and post-test data obtained in control periods of air breathing. Alternations in all ventilatory components except fR changed significantly during FI,O2 alternations; VT 26%, tE-8%, VT/tI 18%, tI/ttot 11% and V'E 28% of baseline values. Within and between infant variances are reported for the individual components of ventilation. Differences among infants were best detected by alternations in V'E; within infant variance 76, between infant variance 171. We conclude that the test described is a safe, reliable and relatively easily applied method of measuring peripheral chemoresponsiveness, which is suitable for clinical application in infancy.

Analysis of Variance↗
PubMed1996

The role of public policy in health care market change.

Market forces appear dominant in the transformation of health care systems across the United States. However, in many markets public policy remains an important factor--guiding, facilitating, and in some cases prompting change. This paper reviews how the debate over health care reform acted as a catalyst in local health care financing and delivery systems, and how other public policy tools are affecting the fifteen markets studied in the Community Snapshots project. We then discuss prospects for public policy in the near term and the longer term, using two scenarios to illustrate possible future roles.

Community Health Planning↗
PubMed1996

Principal components analysis of the Physical Self-Efficacy Scale for a black sample.

Principal components analysis of an intercorrelation matrix for the Physical Self-efficacy Scale in an all black sample of 320 mostly confirmed the original validation study of Ryckman, Robbins, Thornton, and Cantrell who used a wholly white sample; however, the analysis identified items with factor loadings at criterion on more than one factor, one item that loaded on a different subscale, and additional factors. It is unknown whether differences in this sample are attributable to race or other influences. Further investigation is suggested.

Adolescent↗
PubMed1996

Effects of the callipyge phenotype on serum creatinine, total cholesterol, low-density lipoproteins, very-low-density lipoproteins, high-density lipoproteins, and triacylglycerol in growing lambs.

The goals of this study were to investigate the effects of the callipyge (CLPG) phenotype on serum creatinine and lipid profiles of growing lambs. Preliminary studies in our laboratories indicated that creatinine may have utility in distinguishing the CLPG phenotype and that expression of the CLPG gene altered concentrations of serum total cholesterol (TC). As a result, in this study, we examined the influence of the CLPG gene on concentrations of creatinine, TC, very-low-density lipoproteins (VLDL), low-density lipoproteins (LDL), high-density lipoproteins (HDL), and triacylglycerol (TG) at varying stages of maturity in lambs. Ten homozygous (c/c) Polypay ewes were crossed with Dorset rams heterozygous for the CLPG gene (C/c). From this cross, 20 lambs (13 females and 7 males) were born, of which 11 were homozygotic (c/c) and 9 were heterozygotic (C/c; CLPG) based on muscle weights and longissimus dorsi (LD) area at slaughter. Blood samples were taken at monthly intervals and serum lipid constituents were assayed. At 1 mo of age, no differences (P > .05) in plasma lipids were detectable between phenotypes. However, at 2 mo age, CLPG lambs had higher (P < .01) concentration of TG, TC, HDL, and VLDL compared to homozygotic (c/c) lambs. Triglycerides and VLDL were elevated (P < .05) in CLPG lambs at 3 mo of age. By slaughter, no differences (P > .05) in serum lipid constituents were detectable between genotypes. Hence, the increase in serum TC is due to elevated levels of HDL and VLDL. These observations indicate that creatinine may be used to distinguish CLPG lambs and that the CLPG gene alters serum lipid profiles during the postnatal period.

Aging↗
PubMed1996

A uveitis register at the Leicester Royal Infirmary.

In the study of uveitis, epidemiology is frequently neglected. Our uveitis register consisted of data collected on all uveitis patients except minor, easily resolved, anterior uveitis cases at the Leicester Royal Infirmary. The diagnoses of these patients were classified by the aetiological method. A total of 712 patients was entered into the register over a period of 10 years starting from January 1985. In the study, 73.0% of the cases fit into named clinical syndromes while 27.0% of the cases were diagnosed as idiopathic but uncategorised. The commonest definable cause of anterior uveitis was HLA-B27-related acute anterior uveitis, comprising 15.2% of all uveitis cases. Intermediate uveitis accounted for 7.9% of all cases while the commonest definable cause of posterior uveitis was toxoplasmosis, forming 4.6% of all uveitis cases. The aim of the study was to present data relating to diagnostic categories from a primary and secondary uveitis clinic, and to explore the usefulness of such a uveitis register within an ophthalmic department.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Localization of ribosomal RNA and Pbs21-mRNA in the sexual stages of Plasmodium berghei using electron microscope in situ hybridization.

A reproducible technique for the ultrastructural localization of RNAs in malaria parasites has been developed which combines excellent structural preservation with high hybridization signals. Signals obtained following in situ hybridization with an antisense rRNA probe which recognizes all forms of small subunit (SSU) rRNA correlate with the density of ribosomes in the parasite cytoplasm and show that a) the male gametocyte has only 12 to 25% the ribosomes found in the female cell and asexual parasite and b) the probe did not hybridize with an electron-dense nuclear body previously called a nucleolus. We suggest this structure is either a transcription-, or a replication-factory. Using a probe for the sexual stage-specific protein Pbs21 mRNA, signal was found only in female gametocytes, zygotes and ookinetes and showed a non-random, clumped cytoplasmic distribution. It is not known at present whether the non-random distribution of the Pbs 21 mRNA is critical to the very delayed translation of the Pbs21 message into protein, which occurs only in the zygote and ookinete.

Animals↗
PubMed1996

High-frequency oscillatory ventilation in pediatric patients.

High-frequency oscillatory ventilation (HFOV) offers the potential to maintain adequate gas exchange without imposing the large pressure swings and tidal volumes associated with ventilatory-induced lung injury. This article reviews the studies evaluating the use of HFOV to treat pediatric respiratory failure, discusses the complications associated with HFOV, and details an approach to the practical application of HFOV in the non-neonatal pediatric population.

Adolescent↗
PubMed1995

An anti-CD3 single-chain immunotoxin with a truncated diphtheria toxin avoids inhibition by pre-existing antibodies in human blood.

Diphtheria toxin (DT) is often used in the construction of immunotoxins. One potential problem using DT-based immunotoxins is the pre-existing anti-DT antibodies present in human blood due to vaccination. The present study examined the effect of human serum with pre-existing anti-DT antibodies on the toxicity of UCHT1-CRM9, an immunotoxin directed against CD3 molecules on T-lymphocytes. Sera with detectable anti-DT antibodies at 1:100 or greater dilutions inhibited the immunotoxin toxicity. Experiments with radio-labeled UCHT1-CRM9 indicate that anti-DT antibodies partially block its binding to the cell surface as well as inhibit the translocation from the endosome to the cytosol. The inhibitory effect could be adsorbed using a full-length DT mutant or B-subfragment. A C-terminal truncation mutant could not adsorb the inhibitory effect, suggesting that the last 150 amino acids contain the epitope(s) recognized by the inhibitory antibodies. Therefore, an anti-CD3 single-chain immunotoxin, sFv-DT390, was made with a truncated DT. The IC50 of sFv-DT390 was 4.8 x 10(-11) M, 1/16 the potency of the divalent UCHT1-CRM9. More importantly, sFv-DT390 toxicity was only slightly affected by the anti-DT antibodies in human sera.

Antibodies, Bacterial↗