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Biomedical subjects

D R Johnson

Publications and source records attributed to D R Johnson.

At least 145 records · Page 8Linked to original sources
PubMed1993

Endothelial activation by hydrogen peroxide. Selective increases of intercellular adhesion molecule-1 and major histocompatibility complex class I.

Products of activated leukocytes may alter vascular endothelial cell (EC) function. For example, ECs respond to leukocyte-derived cytokines, such as tumor necrosis factor (TNF) or interleukin-1, by reversibly altering levels of expression of specific gene products that promote inflammation. In contrast, hydrogen peroxide, a product of TNF-activated neutrophils, can produce irreversible EC injury and death. In this study, we have investigated the effects of subinjurious concentrations of hydrogen peroxide on EC inflammatory functions. Treatment with 50 to 100 mumol/L hydrogen peroxide selectively increases surface expression of intercellular adhesion molecule-1 and major histocompatibility complex class I, but not endothelial leukocyte adhesion molecule-1 (also known as E-selectin), vascular cell adhesion molecule-1, or gp96, a constitutively expressed EC surface protein. Increased major histocompatibility complex class I and intercellular adhesion molecule-1 surface expression is associated with specifically increased messenger RNA levels, suggesting selective endothelial gene activation. Hydrogen peroxide does not activate the transcription factor Nuclear Factor kappa B, an important mediator of TNF-induced gene expression. Co-treatment with hydrogen peroxide inhibits TNF-induced gene expression at 4 hours, an effect which can be attributed to reversible inhibition of TNF binding to EC surface receptors. Hydrogen peroxide also antagonizes the actions of interleukin-1. At 24 hours, TNF and hydrogen peroxide produce, at most, additive increases in intercellular adhesion molecule-1 and major histocompatibility complex class I. These results suggest that subinjurious concentrations of hydrogen peroxide can activate endothelium and that the effects of hydrogen peroxide on ECs differ from those of inflammatory cytokines.

Antigens, Surface↗
PubMed1993

Tissue factor and the extrinsic pathway of coagulation during infection and vascular inflammation.

Tissue factor is a potent initiator of blood coagulation. In tissue sections, it has been immunologically demonstrated in cells normally not in contact with circulating blood, and elevated activity has been repeatedly demonstrated in peripheral blood monocytes of patients considered to be at risk for thrombosis. Studies with endothelial cells and monocytes in culture have documented the induction of tissue factor synthesis by biochemical mediators of the inflammatory process. Lytic processes, such as those caused by complement activation or viral infections, increase the tissue factor activity several fold over the basal level of the affected cells. Diminished anti-thrombotic properties of endothelium, and induced tissue factor expression in endothelium and monocytes/macrophages, combined with the increased specific procoagulant activity resulting from cell membrane damage, may endow inflammatory foci with dramatically elevated procoagulant activity. Levels of tissue factor activity at which procoagulant mechanisms escape regulation by natural anticoagulant mechanisms and produce thrombosis remain to be determined.

Blood Coagulation↗
PubMed1993

Duration of positive throat cultures for group A streptococci after initiation of antibiotic therapy.

OBJECTIVE: To determine if it is appropriate to recommend that patients with group A beta-hemolytic streptococcal pharyngitis, who are clinically well by the morning after starting antibiotic treatment, can return to school or day care, or if they should wait until they have completed 24 hours of antibiotics as recommended by the American Academy of Pediatrics Committee on Infectious Diseases. METHODS: We examined the duration of positivity of the throat culture after antibiotics were begun as a means of assessing the potential risk of transmission to close school contacts. Forty-seven children (4 to 17 years of age) with pharyngitis and a positive throat culture for group A streptococci in an outpatient, staff model health maintenance organization clinic were enrolled and were randomly selected to receive therapy with either oral penicillin V, intramuscular benzathine penicillin G, or oral erythromycin estolate. Additional throat cultures were obtained and clinical findings were recorded for each child during three home visits in the 24 hours after their initial clinic visit. Acute and convalescent sera were obtained for determination of anti-streptolysin O and anti-DNase B titers. RESULTS: Seventeen (36.2%) of the 47 patients had a positive culture the morning after initiating antibiotic therapy. However, thirty-nine (83%) of the patients became "culture negative" within the first 24 hours. Neither the time interval to the first negative culture nor the presence or absence of group A streptococcal organisms on any single convalescent culture could be predicted by clinical findings. Six of the eight children who failed to convert to a "negative" throat culture within 24 hours of initiating therapy were receiving erythromycin. We could detect no difference in either time to conversion to a negative culture or the presence of a positive culture 24 hours after starting antibiotics between those who demonstrated a significant antibody increase and those who did not. CONCLUSION: The data from this study strongly suggest that children with group A beta-hemolytic streptococcal pharyngitis should complete a full 24 hours of antibiotics before returning to school or daycare.

Adolescent↗
PubMed1993

The inheritance of vertebral shape in the mouse. II. A study using Fourier analysis to examine the inheritance of patterns of vertebral variation in the cervical and upper thoracic vertebral column.

In this paper we continue an earlier study which examined shape differences between the cervical and upper thoracic vertebrae of 2 inbred strains of mice (CBA, C57BL) and their F1. Our earlier study showed that the amount of shape difference varied between different vertebrae, even from adjacent levels, and that the vertebrae of the F1s showed a degree of resemblance to one or other parental strain which varied from vertebral level to vertebral level. We have suggested that this variation from level to level may have evolutionary significance in that it demonstrates a degree of autonomy in the genetic control of vertebral morphology between successive levels and, as such, allows the possibility of a form of mosaic evolution. In this study we further consider the inheritance of vertebral morphology both in the above-mentioned and in other crosses: this time, however, we focus on the ways in which vertebral morphology changes from level to level and on any differences in patterns of metameric change between inbred strains and their offspring. Our findings indicate that the morphology of vertebrae shows a metameric gradation in shape and that the rates of shape change along the column can vary from region to region. Furthermore, the F1 between 2 inbred strains may follow the pattern of variation characteristic of one parent for several metameric segments at a time. Different crosses between different inbred strains indicate that many genes influence the pattern of metameric variation in the vertebral column and that these genes have different actions along the column.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Cytokines increase transporter in antigen processing-1 expression more rapidly than HLA class I expression in endothelial cells.

Transporter in Ag processing-1 (TAP-1, previously called PSF-1 or Ring-4) is an MHC-encoded gene product that is required for efficient association of intracellular peptide Ag with nascent HLA class I H chain and beta 2-microglobulin, thereby permitting assembly and normal surface expression of the class I molecules. TAP-1 is thought to function as a component of a transmembrane pump, that transports cytoplasmically-derived peptides into the lumen of the endoplasmic reticulum where class I molecules assemble. Synthesis and expression of HLA class I molecules is increased in human endothelial cells by IFN-beta, IFN-gamma, and TNF. We report these same cytokines increase TAP-1 expression. As with class I, TAP-1 is also synergistically increased by combinations of TNF with IFN. Interestingly, cytokine-induced increases in TAP-1 mRNA are markedly more rapid than increases in class I mRNA. This rapid increase in TAP-1 mRNA is reflected in a rapid increase in TAP-1 protein. These results demonstrate that TAP-1 synthesis and class I synthesis are regulated in parallel. The rapidity of the cytokine response of TAP-1 compared to class I further suggests that the constitutive level of TAP-1 expression in endothelial cells is not sufficient to support inducible increases in class I expression.

Animals↗
PubMed1992

Production of pyrogenic exotoxins in group A streptococci isolated from patients in Zagreb, Croatia.

The pyrogenic exotoxin profiles were determined of group A streptococci isolated from patients in Zagreb, Croatia in the period 1989-1990. A total of 12 strains were studied, five from patients with serious infections and seven from patients with uncomplicated infections. Serotypes M1 and M3 were found in seven (58%) patients. Seven strains produced exotoxin A and ten strains exotoxin B. The proportion of exotoxin A and B producing strains in patients with severe infections (3 patients respectively) was similar to that found in patients with uncomplicated infections (4 and 7 patients respectively).

Adult↗
PubMed1992

An automated method for the analysis of trabecular bone structure.

Trabecular structure as well as bone mass is important in studies of bone disease and fracture. An automated method for the direct analysis of two-dimensional trabecular micro-anatomy and its application to human iliac crest bone biopsies is described. Compared with established methods which require expensive equipment and complex software, costs have been reduced and availability increased by using an image analyzer driven by a microcomputer. Routine histological sections are accepted and an editing function enables the removal of artifacts. An elastic window allows field expansion for large specimens. The program enables the rapid assessment of the bone volume and trabecular surface from the intact image, followed by image skeletonization and the deduction of the trabecular length, number, character, and spacing together with the number of trabecular junctions and discontinuities; the trabecular width is calculated indirectly. Images may be stored to disk or printed as permanent records for diagnostic or research purposes.

Biopsy↗
PubMed1992

Adenosine use in pregnancy: lack of effect on fetal heart rate.

The treatment for supraventricular tachycardia in pregnancy is somewhat controversial. Although a variety of medications have been used to terminate this rhythm during pregnancy, all have actual or theoretical drawbacks. Adenosine is a relatively new medication with an extremely short half-life and is effective in the treatment of supraventricular tachycardia. We report a case in which this medication was used successfully during pregnancy. In addition, we found that adenosine had no effect on fetal heart rate in this case.

Adenosine↗
PubMed1992

Delayed detection of an increase in resistant Acinetobacter at a Detroit hospital.

OBJECTIVE: To study an increase of antimicrobial-resistant Acinetobacter baumannii and to assess reasons for the delayed detection of this increase. DESIGN: Review of medical, laboratory, and infection control records. Plasmid profile analysis of available A baumannii isolates. SETTING: A 340-bed trauma and intensive care hospital in Detroit, Michigan. RESULTS: The number of hospitalized patients with resistant A baumannii increased during late 1989 and early 1990: 4 in September, 10 in October, 12 in November, 18 in December, and 23 in January (chi square for trend = 14.6, p = .0001). Forty-four (66%) of the 67 patients culture-positive for resistant A baumannii had respiratory tract colonization or infection. Of 11 resistant isolates, 6 had a similar plasmid profile and 5 had no plasmids. Under the hospital's targeted surveillance system, only positive cultures from blood or wounds were investigated; this largely respiratory increase of resistant A baumannii went unrecognized until January 1990. CONCLUSIONS: Antimicrobial resistance in A baumannii is an important concern. Such resistance is not necessarily plasmid mediated. Targeted surveillance for this and other agents of nosocomial infection should be used with caution, particularly in hospitals with many debilitated patients.

Acinetobacter↗
PubMed1992

Epidemiologic analysis of group A streptococcal serotypes associated with severe systemic infections, rheumatic fever, or uncomplicated pharyngitis.

More than 1100 group A streptococcal isolates collected in the United States (1988-1990) were examined to document an association of individual serotypes with specific clinical infections during the recent resurgence of group A infections and their sequelae. The most commonly isolated strains from patients with only uncomplicated streptococcal pharyngitis ("control" strains) were M serotypes 1, 2, 4, and 12. M1, M3, and M18 were statistically significantly more frequently isolated from patients with serious invasive infections and M3 and M18 from patients with rheumatic fever compared with the distribution of serotypes from the 866 control strains. An unexpected and important finding indicated that isolation rates of M1 streptococci varied geographically within the United States by year. The propensity for M1 streptococci to be statistically associated with severe systemic infections appeared unrelated to the M1 isolation rates from patients with only uncomplicated pharyngitis, thus offering additional support for the concept of strain-associated virulence rather than virulence broadly related to a given serotype.

Adult↗
PubMed1992

M protein gene typing of Streptococcus pyogenes by nonradioactively labeled oligonucleotide probes.

A new approach for the typing of Streptococcus pyogenes is described. Oligonucleotide probes of 30 nucleotides in length were derived from currently known sequences of the N-terminal regions of M protein genes (emm genes). The oligonucleotides were labeled with digoxigenin-dUTP and hybridized to dot-blotted genomic DNA from 116 group A streptococcal strains of serotypes M-1, M-2, M-3, M-5, M-6, M-12, M-18, M-19, M-24, and M-49. Hybridization reactions were visualized with a chemiluminescent substrate. In comparison with conventional serological typing of expressed M proteins, the binding of the probes to the corresponding emm genes exhibited 100% sensitivity and specificity. The results emphasize the high degree of type-specific conservation of the N-terminal regions of emm genes from reference strains and epidemiologically unrelated U.S. and European clinical isolates. The existence of two distinct genetic subgroups among eight investigated M-49 strains was unequivocally shown by hybridization assays and further confirmed by nucleotide sequence data obtained from four selected M-49 strains. Because oligonucleotide probes are relatively easy to prepare, easy to handle, and known to give consistent interlaboratory results, the "oligotyping" technique appears to offer potential advantages over conventional serological typing methods.

Antigens, Bacterial↗
PubMed1992

Skeletal variations of the seventh cervical vertebrae in the mouse with special reference to the foramina transversaria and the accessory foramina.

The formation of foramina transversaria in the seventh cervical vertebra of CBA and C57BL mice and their offspring is found to behave as if it is determined by a single semi-dominant gene. The accessory foramina of Weber (1950) are investigated in the same material. These foramina are classified into two types and their heredity is evaluated.

Animals↗
PubMed1992

A comparison of group A streptococcal serotypes isolated from the upper respiratory tract in the USA and Thailand: implications.

Characterization of group A beta-haemolytic streptococci in upper respiratory tract isolates from the USA and Thailand revealed that whereas 80% of the U.S. isolates could be M or opacity factor (OF) typed, less than 20% of the Thai isolates could be characterized with the available typing sera (P less than 0.001). There was also a statistically significant difference observed in the percentage of strains that could be characterized by the T-agglutination pattern (93% in the USA vs 61% in Thailand, P less than 0.001). Even among the identifiable strains, marked differences in the distribution of the recovered serotypes were noted between the two countries. These results show that there are a significant number of as yet unidentified group A streptococcal strains in parts of the world where streptococcal infections and their sequelae are important public health problems. They further imply that such findings must be taken into consideration in the future when designing possible streptococcal vaccines for worldwide use.

Child↗
PubMed1992

Efficacy of Bacillus thuringiensis var. israelensis against larvae of the southern buffalo gnat, Cnephia pecuarum (Diptera: Simuliidae), and the influence of water temperature.

Susceptibility of southern buffalo gnat larvae to Bacillus thuringiensis var. israelensis (B.t.i.) was studied during 1986-88. Tests were conducted using Vectobac 12AS in a mini-gutter aquatic bioassay system. Mini-gutter tests using a 4.5 ppm B.t.i. concentration and a 10 min exposure period confirmed a positive correlation between water temperature and B.t.i. effectiveness. Significantly lower larval mortality occurred as water temperature decreased below 9 degrees C, indicating that proper timing of B.t.i. application is essential to maximize larval control. Even with this temperature limitation, larval control using B.t.i. should provide an economically effective means of preventing outbreaks of the southern buffalo gnat.

Animals↗
PubMed1992

The inheritance of vertebral shape in the mouse. I. A study using Fourier analysis to examine patterns of inheritance in the morphology of cervical and upper thoracic vertebrae.

The shapes of cervical and upper thoracic vertebrae from large samples of 2 inbred strains of mice and their F1 offspring were examined using Fourier analysis to investigate in detail the distributions and magnitudes of differences in vertebral shape between different strains of mice, the relationships between parents and offspring and any differences in the inheritance of vertebral shape between successive vertebral levels. Consistent with the findings of an earlier study there was evidence for considerable differences between vertebral levels in the degree to which offspring resemble one or other parent. The results demonstrate that the inheritance of vertebral morphology conforms to a model in which F1s between inbred strains form a triangular relationship with their parents. Furthermore, this relationship varies between vertebral levels. The significance of these findings is considered in relation to the understanding of the mechanisms of character inheritance and evolution and some new directions for research into vertebral column morphogenesis are proposed.

Animals↗
PubMed1991

Tumor necrosis factor induction of endothelial cell surface antigens is independent of protein kinase C activation or inactivation. Studies with phorbol myristate acetate and staurosporine.

We have investigated whether TNF-induced changes in human endothelial cell (EC) surface Ag expression are mediated by protein kinase C (PKC). This suggestion arose from the observations that PMA, a potent PKC activator, can mimic TNF by inducing expression of endothelial leukocyte adhesion molecule 1, intercellular adhesion molecule 1 (ICAM-1), and class I MHC molecules on human EC. However, in contrast to the actions of PMA, TNF neither causes membrane translocation of PKC nor induces the phosphorylation of the myristoylated alanine-rich C kinase substrate, two measures of PKC activation. Moreover, the PKC inhibitor staurosporine can block PMA-induced endothelial leukocyte adhesion molecule 1 expression at 4 h, but does not inhibit the actions of TNF. At 24 h, staurosporine itself induces intercellular adhesion molecule 1 and class I MHC, and acts additively with TNF. Twenty four hour treatment with PMA causes loss of PKC. We propose that at 24 h, staurosporine and PMA share a mechanism of action, namely diminution of PKC activity. However, 24 h treatment with TNF does not reduce the amount of PKC nor does it prevent activation of PKC by PMA. We conclude that TNF effects in EC are not mediated by PKC activation or inactivation.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1991

An outbreak of shigellosis at an outdoor music festival.

In August 1988, an estimated 3,175 women who attended a 5-day outdoor music festival in Michigan became ill with gastroenteritis caused by Shigella sonnei. Onset of illness peaked 2 days after the festival ended, and patients were spread throughout the United States by the time the outbreak was recognized. An uncooked tofu salad served on the last day was implicated as the outbreak vehicle (odds ratio = 3.4, p less than 0.0001). Over 2,000 volunteer food handlers prepared the communal meals served during the festival. This large foodborne outbreak had been heralded by a smaller outbreak of shigellosis among staff shortly before the festival began and by continued transmission of shigellosis from staff to attendees during the festival. S. sonnei isolated from women who became ill before, during, and after the festival had identical antimicrobial susceptibility patterns and plasmid profiles. Limited access to soap and running water for handwashing was one of the few sanitary deficits noted at this gathering. This investigation demonstrates the need for surveillance and prompt public health intervention when Shigella infections are recognized in persons attending mass outdoor gatherings, the singular importance of handwashing in reducing secondary transmission of shigellosis, and the potential for explosive outbreaks when communal meals are prepared by large numbers of food handlers.

Adult↗