PubMed HealthSearch

Biomedical subjects

D R Johnson

Publications and source records attributed to D R Johnson.

At least 19 recordsLinked to original sources

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

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

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

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

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

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

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

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

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

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

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

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

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

Binding and multiple hydrolytic sites in epitopes recognized by catalytic anti-peptide antibodies.

Autoantibodies purified from humans catalyse the hydrolysis of the neurotransmitter, vasoactive intestinal peptide (VIP). Evidence that the hydrolysis of VIP is due to antibodies includes: the antibody preparations are free of detectable non-immunoglobulin (non-Ig) contamination; the hydrolytic activity is removed by precipitation with anti-human IgG antibody; human B lymphoblastoid cells transformed with Epstein-Barr virus secrete hydrolytic antibodies in culture; the Fab fragments of the antibodies exhibit VIP hydrolysis; and affinity chromatography on immobilized VIP permits purification of specific antibodies with greatly enriched hydrolytic and binding activities. One of the catalytic antibody preparations hydrolyses the Gln-16-Met-17 bond. Studies with synthetic VIP fragments showed that the epitope recognized by this antibody is formed by VIP(15-28). Important binding interactions are contributed by VIP(22-28), a sequence four residues distant from the scissile bond. Antibodies from a second subject hydrolyse six peptide bonds in VIP, clustered between residues 14 and 22. These bonds link amino acids of different charge, size and hydrophobicity, suggesting that the hydrolytic repertoire of the antibodies is considerable. The antibodies do not hydrolyse peptides unrelated in sequence to VIP. Cleavage of several peptide bonds in VIP by polyclonal antibody preparations may be due to several antibodies, each with a unique cleavage specificity. Alternatively, a single antibody may make catalytically productive contact at multiple peptide bonds in the substrate, because of conformational flexibility of VIP or of the antibody active site. Purified light chains from the catalytic antibodies hydrolysed VIP more rapidly than did intact antibodies. The residues constituting the catalytic site of an antibody may be encoded in germline V-region genes or may arise during maturation of the antibody response.

Amino Acid Sequence

Medical problem solving and uncertainty in the emergency department.

STUDY OBJECTIVE: To compare the diagnostic processes of experienced emergency physicians with those of novices. DESIGN: Prospective, convenience sample of patients. SETTING: Emergency department of a county university medical center in a large southwestern urban community. PARTICIPANTS: Experienced emergency physicians (attending and senior residents) and novice clinicians (junior residents and senior medical students). INTERVENTIONS: Participants developed initial diagnostic impressions after reviewing the chief complaint, nurse triage notes, and vital signs. Tests were then selected, and a final diagnostic impression was identified after results were known. Clinicians also marked a visual analog scale corresponding to their estimate that each diagnostic possibility was correct. RESULTS: Experienced physicians increased their certainty more than novices (P = .014). They deviated from a standard history-physical-laboratory sequence more often than novices (P = .008). CONCLUSION: Expertise in medical decision making is characterized by a moderate initial level of certainty concerning a diagnosis that significantly increases as the experienced clinician follows a flexible strategy of testing to arrive at a final diagnosis.

Academic Medical Centers