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Biomedical subjects

D R Johnson

Publications and source records attributed to D R Johnson.

At least 127 records · Page 7Linked to original sources
PubMed1994

HLA class I heavy-chain gene promoter elements mediating synergy between tumor necrosis factor and interferons.

The cytokines tumor necrosis factor (TNF), beta interferon (IFN-beta), and IFN-gamma increase major histocompatibility complex class I molecule expression. A greater than additive (i.e., synergistic) induction of class I heavy-chain mRNA is observed in HeLa cells treated with TNF in combination with either type of IFN. To define the cis-acting elements mediating cytokine synergy, the promoter of a human major histocompatibility complex class I heavy-chain gene (HLA-B7) was placed in front of a reporter gene and transfected into HeLa cells. Deletion analysis mapped the elements required for synergy to a 40-bp region containing a kappa B-like element, which is necessary for the response to TNF, and an interferon consensus sequence (ICS), which is necessary for the responses to IFNs. When the orientation of these elements was reversed or their normal 20-bp spacing was reduced by 5 or 10 bp, i.e., one half or one full turn of the DNA helix, essentially equivalent responses were obtained, suggesting that these parameters are not critical. In electromobility shift assays, a p50-containing NF-kappa B nuclear factor from TNF-treated cells binds kappa B-containing probes, and ISGF-2 from IFN-gamma-treated cells binds ICS-containing probes. A probe containing both the kappa B and ICS elements (kappa B-ICS) forms a novel complex with nuclear factors isolated from cells treated with both TNF and IFN-gamma; this complex also forms when nuclear factors from individually cytokine-treated cells are mixed in vitro. The natural variant ICS found in HLA-A responds to IFN-gamma and can mediate synergy with TNF. However, the variant kappa B found in HLA-C does not respond to TNF, nor can it mediate synergy between TNF and IFN-gamma. These observations suggest that synergy between TNF and IFNs in the induction of HLA class I gene expression results from the sum of individual interactions of cytokine-activated enhancer-binding factors with the transcription initiation complex.

Base Sequence↗
PubMed1994

Bronchoscopy-associated Mycobacterium xenopi pseudoinfections.

Mycobacterium xenopi typically accounts for less than 0.3% of all clinical mycobacterial isolates. Over a 37-mo period, 21 (35%) of 60 mycobacterial isolates from a Michigan hospital were identified as M. xenopi. Hospital, laboratory, and bronchoscopy records were reviewed to determine case characteristics, develop a case series, and calculate procedure-specific M. xenopi isolation rates. A case-control study was conducted to elucidate aspects of the bronchoscopy procedure associated with M. xenopi isolation. Bronchoscope cleaning procedures were reviewed, and hospital water systems were cultured. Four isolates were from three patients with disease attributable to M. xenopi. Of the other isolates, specimens obtained by bronchoscopy were more likely to yield M. xenopi than were specimens obtained by other routes (relative risk, 9.7; 95% confidence intervals, 3.2, 29.6). Bronchoscopes were disinfected in a 0.13% glutaraldehyde-phenate and tap-water bath and then were rinsed in tap water. Water from the hot water tank supplying this area yielded M. xenopi. Mycobacteria were cultured from bronchoscopes after disinfection. M. xenopi in the tap water appears to have contaminated the bronchoscopes during cleaning. Adequate disinfection of contaminated bronchoscopes and careful collection of specimens to avoid contamination with contaminated water are essential, both for limiting diagnostic confusion caused by mycobacterial pseudoinfections and for reducing risks of disease transmission.

Adult↗
PubMed1994

Behaviorally conditioned modulation of natural killer cell activity: effects of pre-conditioning manual restraint and apparatus exposure.

This study investigated behaviorally conditioned modulation of natural killer cell (NK) activity. One and three trial behavioral conditioning training trial designs were examined. In addition, the influence of pre-conditioning exposure to manual restraint and the conditioning apparatus upon behaviorally conditioned natural killer cell responses was assessed. Prior to one trial training, animals were exposed to either the conditioning apparatus, manual restraint, or were undisturbed. The animals were then trained to associate the conditioned stimulus (CS) and the unconditioned stimulus (US), and later re-presented with the CS. Behaviorally conditioned animals demonstrated significantly enhanced NK cell activity, no difference in NK activity, or significantly decreased NK activity, respectively. There was also a significant interaction between the manual restraint and behavioral conditioning interventions. Animals in a three training trial design were either manually restrained daily prior to and during behavioral conditioning or were left undisturbed. In this design behavioral conditioning significantly decreased NK cell activity and manual restraint significantly increased NK cell lytic activity. These data illustrate behaviorally conditioned decreases and increases in NK cell lytic activity dependant upon the experimental design. Behaviorally conditioned NK cell activity is influenced by additional behavioral interventions (i.e. manual restraint and novelty of conditioning environment) inherent within the behavioral conditioning procedures.

Animals↗
PubMed1994

Behaviorally conditioned modulation of natural killer cell activity: enhancement of baseline and activated natural killer cell activity.

Natural killer (NK) cells comprise a sub-population of lymphocytes functionally defined by their ability to spontaneously lyse select tumor and virally infected cells. NK cell lytic function is sensitive to modulation by cytokines and neuroendocrine mediators. Behavioral conditioning trains an animal to cognitively associate a novel environmental cue (i.e. odor) with a physiologically active agent (i.e. Polylnosinic:PolyCytidilic acid, Poly I:C). Poly I:C induces interferon production resulting in activation of NK cells and enhanced NK cell lytic activity. Subsequent to behavioral conditioning, independent presentation of the odor should elicit similar responses (enhanced NK cell activity). We have shown that animals pre-exposed to the conditioning apparatus or manual restraint prior to behavioral conditioning demonstrate enhanced baseline NK cell activity or no effects respectively. To assess the influence of NK cell activation in conjunction with behavioral conditioning, we have re-presented the odor to animals with activated or baseline NK activity. Lymphocytes were then incubated for five days with IL-2 and cellular cytotoxic activity re-assessed. Behavioral conditioning significantly enhanced baseline and activated NK cell activity in animals previously exposed to the conditioning apparatus. No differences in lytic activity versus NK sensitive targets were observed following IL-2 activation. In contrast, animals manually restrained prior to conditioning showed no differences in baseline or in vivo activated NK activity, but previously non-activated lymphocytes stimulated with IL-2 demonstrated significantly higher lytic activity in conditioned animals re-presented with the odor. These results demonstrate central nervous system (CNS) modulation of NK cell activity and the presence of an interplay between cytokine activation and responsiveness to CNS immunoregulatory signals.

Animals↗
PubMed1993

Differential induction of VCAM-1 on human iliac venous and arterial endothelial cells and its role in adhesion.

Venous and arterial large vessel endothelial cells (EC) were compared for their constitutive and TNF-alpha-induced expression of the cell-surface adhesion molecules ICAM-1 and -2, VCAM-1 and ELAM-1 by FACS analysis. Human iliac venous and arterial EC (HIVEC and HIAEC) constitutively express ICAM-1 and ICAM-2. TNF-alpha increases the expression of ICAM-1, but not ICAM-2, and induces the expression of ELAM-1 on both EC types. However, TNF-alpha induces VCAM-1 cell-surface expression and mRNA only in venous, but not in arterial EC. We next investigated the function of these adhesion molecules and their ligands, LFA-1, very late activation Ag (WLA-L) and sialylated Lewis x glycoprotein (sLe(x)), in adhesion assays with the monocyte-like cell line U937. Untreated U937 cells do not adhere to untreated HIVEC or HIAEC and adhesion is much lower to TNF-alpha-treated arterial than to TNF-alpha-treated venous EC. In adhesion-inhibition assays we demonstrate that U937 cell adhesion to TNF-alpha-treated HIVEC is mediated by VCAM-1/VLA-4 and ELAM-1/sLe(x) interaction, whereas the lower adhesion to TNF-alpha-treated HIAEC is only mediated by ELAM-1/sLe(x) interaction. U937 cells treated with the phorbol ester PMA for 3 days adhere to both HIVEC and HIAEC; this adhesion is mediated by LFA-1 interaction with ICAM-1 and/or -2. Adhesion of PMA-treated U937 cells is increased by TNF-alpha treatment of EC. This increased adhesion is mediated in part by the TNF-alpha-induced VCAM-1 expression on venous EC. Therefore, the cell-surface adhesion molecule VCAM-1 is differentially induced on these two EC types and the differential expression is functionally important in U937 cell adhesion.

Adult↗
PubMed1993

Four different classes of inhibitors of receptor-mediated endocytosis decrease tumor necrosis factor-induced gene expression in human endothelial cells.

We have investigated the relationship between receptor-mediated endocytosis of TNF and TNF-induced gene expression in cultured human endothelial cells. Exposure of cells to hypertonicity, to cytoplasmic acidification, to treatment with phenylarsine oxide, or to treatment with primary amines such as putrescine or dansylcadaverine each inhibited receptor-mediated endocytosis by 30 to 75%, as measured by uptake of acetylated Dil-low density lipoprotein or of 125I-TNF. All four treatments also inhibited TNF-induced surface expression of ELAM-1 by 50 to 100%. Among these four treatments, only hypertonicity inhibited pinocytosis, as measured by uptake of fluorescein-BSA, and only phenylarsine oxide irreversibly inhibited protein synthesis, as measured by [35S]methionine incorporation. Notably, acidification or treatment with primary amines selectively inhibited the response to TNF, compared with the response to PMA, a drug that induces ELAM-1 through a pathway that bypasses surface receptors. Primary amines, which can be used for sustained periods under physiologic culture conditions without causing toxicity, were investigated further. Pretreatment of endothelial cells with 10 mM putrescine or 100 microM dansylcadaverine also inhibited TNF induction of ICAM-1 expression and VCAM-1 expression. Primary amines also inhibited IL-1-induced increases in ELAM-1, ICAM-1, and VCAM-1 measured 4 to 6 h after treatment and inhibited IFN-beta- and IFN-gamma-mediated induction of class I MHC molecules and IFN-gamma-mediated induction of class II MHC molecules measured 72 h after treatment with cytokine. Levels of mRNA encoding cytokine-inducible molecules were also selectively reduced by primary amines. A constitutively expressed surface molecule, gp96, was not affected in the same cells. These data are consistent with a role for receptor-mediated endocytosis in TNF-mediated gene induction and suggest a new potential target for anti-inflammatory therapy.

Arsenicals↗
PubMed1993

Genetic and biochemical studies of a mutant Saccharomyces cerevisiae myristoyl-CoA:protein N-myristoyltransferase, nmt72pLeu99-->Pro, that produces temperature-sensitive myristic acid auxotrophy.

Saccharomyces cerevisiae myristoyl-CoA:protein N-myristoyltransferase (Nmt1p) is an essential enzyme that transfers myristate from CoA to the amino-terminal glycine residue of at least 12 cellular proteins. Its reaction mechanism is Ordered Bi Bi with myristoyl-CoA binding occurring before binding of nascent polypeptides and release of CoA preceding release of the myristoylprotein product. nmt1-72 is a temperature-sensitive allele, identified by Stone et al. (Stone, D. E., Cole, G. M., Lopes, M. B., Goebl, M., and Reed, S. I. (1991) Genes & Dev. 5, 1969-1981) that causes arrest in the G1 phase of the cell cycle due to reduced acylation of Gpa1p. We have recovered this mutant allele and determined that it contains a single point mutation resulting in a Leu99 (CTA) to Pro (CCA) substitution. Addition of > or = 500 microM myristate but not palmitate to synthetic or rich media rescues the growth arrest caused by nmt1-72 at 37-39 degrees C, consistent with the observation that purified nmt72p has reduced affinity for myristoyl-CoA and that exogenous myristate but not palmitate increases cellular myristoyl-CoA pools. Metabolic labeling studies in S. cerevisiae and co-expression of nmt72p with several protein substrates of Nmt1p in Escherichia coli indicate that the Leu99-->Pro substitution causes a reduction in the acylation of some but not all protein substrates. Since formation of a myristoyl-CoA.Nmt1p complex appears to be required for synthesis/formation of a peptide binding site, these defects in acylation appear to arise either because Leu99 is a component of the enzyme's functionally distinguishable myristoyl-CoA and peptide recognition sites or because Pro99 alters the interaction between myristoyl-CoA and enzyme in a way that precludes formation of a normal peptide binding site. The reduction in affinity for myristoyl-CoA produced by Leu99-->Pro in nmt72p is less than that produced by the Gly451-->Asp mutation in nmt181p, which also produces temperature-sensitive myristic acid auxotrophy. Isogenic, haploid strains containing NMT1, nmt1-72, and nmt1-181 do not manifest any obvious differences in steady state levels of the acyltransferases during growth at permissive temperatures or in the biosynthesis of long chain saturated acyl-CoAs. The spectrum of cellular N-myristoylproteins whose level of acylation is affected by nmt1-72 and nmt1-181 is distinct.(ABSTRACT TRUNCATED AT 400 WORDS)

Acyltransferases↗
PubMed1993

Resuscitation decision making by New Mexico emergency medical technicians.

The extent to which Emergency Medical Service personnel are placed in situations in which difficult cardiopulmonary resuscitation decisions must be made has been poorly explored. Further, it is not known whether this kind of decision making is troubling to emergency medical technicians. Although it is likely that emergency medical service systems handle withholding cardiopulmonary resuscitation in a variety of ways, the authors chose to examine a cross-section of New Mexico emergency medical technicians. Using a survey instrument, emergency medical technicians of all training levels, representing several emergency medical service systems around the state were asked how many times in their career they had been in a situation in which cardiopulmonary resuscitation had been withheld without a direct physician order. Of 310 individuals surveyed, 211 (66.8%) responded that this had occurred at least once. When asked whether they had been troubled by one of these situations, 86 of 211 (41%) individuals responded "yes." When a variety of demographic factors were evaluated, only training to the paramedic level was identified as being an independent predictor of those who were troubled (P = .019). Emergency medical technician training, protocols, and do not resuscitate programs may need to be expanded to give further guidance to prehospital personnel when making difficult resuscitation decisions.

Adult↗
PubMed1993

Cricothyrotomy performed by prehospital personnel: a comparison of two techniques in a human cadaver model.

Little is known about the proficiency of prehospital personnel when performing cricothyrotomies. The authors compared two techniques for establishing an airway through the cricothyroid membrane used by paramedic students. One technique used a prepackaged kit that consisted of a dilator that is passed percutaneously through a breakaway needle. This percutaneous device (PD) was compared with a standard surgical approach (SA) using a scalpel and endotracheal tube. Data was collected on a total of 44 paramedic students who were allowed to attempt each of the procedures. No significant difference in the success rate on the first attempt was found between the two procedures (86% for the SA and 73% for the PD; P = .186). The surgical approach was significantly faster (46 +/- 17 seconds v 103 +/- 62 seconds; P < .01). It was also judged to be significantly easier to perform when evaluated on a linear analog scale (SA, 2.6 +/- 2.0 v PD, 5.1 +/- 2.8; P < .001). Because some procedures were performed on cadavers whose cricothyroid membranes had already been violated, the procedures performed on intact membranes only were also analyzed. Similar, statistically significant differences for insertion time and ease of insertion were again found. Prehospital personnel can be trained to perform cricothyrotomies with a reasonable degree of proficiency. A traditional surgical approach, however, may be faster and less difficult to perform than a comparable procedure using a commercially available percutaneous device.

Airway Obstruction↗
PubMed1993

Direct inoculation of food as the cause of an outbreak of group A streptococcal pharyngitis.

An investigation was conducted of a food-related outbreak of group A streptococcal pharyngitis following an elementary school banquet. Of 166 surveyed banquet attendees, 71 (43%) reported outbreak-associated pharyngitis, and 21 (88%) of 24 tested attendees had evidence of group A streptococcus (GAS) in the throat. Attendees who ate macaroni and cheese were three times more likely to develop pharyngitis than those who did not (66/132 [50%] vs. 5/30 [17%], P = .002). None of the food handlers had GAS recovered by throat culture. However, the cook who prepared the macaroni and cheese had a hand wound; a wound culture grew GAS with the same T agglutination pattern and M- and/or opacity factor type as that of all available GAS strains from ill attendees. Under laboratory conditions, macaroni and cheese supported rapid growth of the outbreak-associated strain of GAS. To the authors' knowledge, this is the first documented foodborne outbreak of GAS pharyngitis in which the only apparent source of contamination was a food handler's skin lesion.

Disease Outbreaks↗
PubMed1993

A review of the correlation of T-agglutination patterns and M-protein typing and opacity factor production in the identification of group A streptococci.

The classical techniques of M protein and opacity factor (OF) typing and T agglutination typing remain the "gold standard" in identifying group A streptococci, although newer techniques have been proposed to assist laboratory scientists, microbiologists, epidemiologists and clinicians in the precise identification and characterisation of these organisms. Because of the current scarcity of M-typing sera and the increased use by many laboratories of T typing as the sole method of group A identification, a table is presented to indicate specific correlation between the T-agglutination pattern and the M serotype. The use of this table will enable not only more selective use of typing sera but also, perhaps, result in improved understanding and ultimately in correlating these defined patterns with newer and more sensitive techniques.

Agglutination Tests↗
PubMed1993

Trauma-related symptoms in veterans of Operation Desert Storm: a preliminary report.

OBJECTIVE: This study was designed to examine prospectively the development of trauma-related symptoms over time in two reserve units of Operation Desert Storm veterans. METHOD: One month and 6 months after returning from the Persian Gulf area, 84 National Guard reservists, from one medical unit and one military police unit, completed questionnaires on their exposure to combat and to specific stressors and rated the severity of their symptoms of posttraumatic stress disorder (PTSD) on two different scales. Differences in symptom severity at the two time points were analyzed. RESULTS: Scores on the Mississippi Scale for Combat-Related Post-Traumatic Stress Disorder, but not severity ratings on a symptom scale based on DSM-III-R PTSD criteria, increased significantly from the 1-month to the 6-month rating time. At both time points, symptoms of hyperarousal were more severe than symptoms of reexperiencing or avoiding trauma-related events. Level of exposure to combat, as reflected by the Combat Exposure Scale and a Desert Storm trauma questionnaire, was significantly associated with score on the Mississippi PTSD scale. There were no significant differences in combat exposure and PTSD symptoms between the male and female subjects or between the medical and police units. CONCLUSIONS: These preliminary findings suggest that a high percentage of Desert Storm veterans experienced some trauma-related symptoms after returning to the United States. Six months after the war, these symptoms, although relatively mild, had not significantly improved in this study group as a whole. For research on longer-term outcome, follow-up of these 84 reservists continues.

Combat Disorders↗
PubMed1993

Childhood physical abuse and combat-related posttraumatic stress disorder in Vietnam veterans.

OBJECTIVE: Early trauma in the form of childhood physical or sexual abuse has been associated with adult psychopathology. The purpose of this study was to compare rates of childhood abuse in Vietnam veterans with and without combat-related posttraumatic stress disorder (PTSD). METHOD: Premilitary stressful and traumatic events including childhood abuse and other potential predisposing factors were assessed in Vietnam combat veterans who sought treatment for PTSD (N = 38) and Vietnam combat veterans without PTSD who sought treatment for medical disorders (N = 28). Stressful and traumatic events including childhood physical abuse were assessed with the Checklist of Stressful and Traumatic Events and a clinician-administered interview for the assessment of childhood abuse. Level of combat exposure was measured with the Combat Exposure Scale. RESULTS: Vietnam veterans with PTSD had higher rates of childhood physical abuse than Vietnam veterans without PTSD (26% versus 7%). The association between childhood abuse and PTSD persisted after controlling for the difference in level of combat exposure between the two groups. Patients with PTSD also had a significantly higher rate of total traumatic events before joining the military than patients without PTSD (mean = 4.6, SD = 4.5, versus mean = 2.8, SD = 2.9). CONCLUSIONS: These findings suggest that patients seeking treatment for combat-related PTSD have higher rates of childhood physical abuse than combat veterans without PTSD. Childhood physical abuse may be an antecedent to the development of combat-related PTSD in Vietnam combat veterans.

Causality↗
PubMed1993

Use of the Structured Clinical Interview for DSM-IV Dissociative Disorders for systematic assessment of dissociative symptoms in posttraumatic stress disorder.

OBJECTIVE: This study compared dissociative symptom areas in Vietnam combat veterans with posttraumatic stress disorder (PTSD) and in Vietnam combat veterans without PTSD. METHOD: The Structured Clinical Interview for DSM-IV Dissociative Disorders (SCID-D) was used to compare dissociative symptoms in 40 Vietnam combat veterans with PTSD and 15 Vietnam combat veterans without PTSD. The SCID-D yields a total score and scores in five symptom areas: amnesia, depersonalization, derealization, identity confusion, and identity alteration. RESULTS: The PTSD patients had more severe dissociative symptoms in each of the five symptom areas of the SCID-D and higher total symptom scores. Amnesia was the symptom area with the greatest difference in scores between the PTSD patients (mean = 3.68, SD = 0.73) and the non-PTSD veterans (mean = 1.06, SD = 0.26). CONCLUSIONS: The finding of higher levels of dissociative symptoms in Vietnam combat veterans with PTSD than in Vietnam veterans without PTSD is consistent with a level of dissociative symptoms in PTSD similar to that in dissociative disorders.

Adult↗
PubMed1993

Deficits in short-term memory in posttraumatic stress disorder.

OBJECTIVE: The purpose of this study was to compare the memory function of patients with posttraumatic stress disorder (PTSD) to that of matched comparison subjects. METHOD: Vietnam veterans with combat-related PTSD (N = 26) were compared to physically healthy comparison subjects (N = 15) matched for age, race, sex, years of education, handedness, socioeconomic status, and alcohol abuse. Memory and intelligence were assessed with a battery of neuropsychological tests, including the Russell revision of the Wechsler Memory Scale, the Selective Reminding Test, and subtests of the Wechsler Adult Intelligence Scale-Revised (WAIS-R). RESULTS: The PTSD patients scored significantly lower than the comparison subjects on the Wechsler Memory Scale logical memory measures for immediate recall (mean = 11.6, SD = 3.3 versus mean = 20.9, SD = 6.6) and delayed recall (mean = 8.0, SD = 3.3 versus mean = 17.8, SD = 6.4). The PTSD patients also scored significantly lower on the total recall, long-term storage, long-term retrieval, and delayed recall measures for the verbal component of the Selective Reminding Test and on the recall, long-term storage, long-term retrieval, and continuous long-term retrieval measures for the visual component of the Selective Reminding Test. There was no significant difference between the PTSD patients and comparison subjects in prorated full-scale IQ as measured by the WAIS-R. CONCLUSIONS: Patients with PTSD may have deficits in short-term memory. Counseling and rehabilitation that address these deficits may be of value for PTSD patients.

Humans↗
PubMed1993

Can the mental representations of paranoid schizophrenics be differentiated from those of normals?

The study of mental representations on projective tests such as the Rorschach has made substantial contributions to our understanding of psychopathology. It is not clear, however, whether the representations of paranoid schizophrenics can be differentiated from those of normals and whether the Rorschach is the best test for such comparison. Object representations on the Rorschach and a role-playing (Johnson & Quinlan, 1980, 1985) test were studied in groups of normal (n = 31) and schizophrenic subjects (divided into paranoid [n = 16], intermediate [n = 11], and nonparanoid groups [n = 16]). Developmental levels of representation on both tests were measured with the widely used system of Blatt, Brenneis, Schimek, and Glick (1976), derived from Werner's concepts of differentiation, articulation, and integration. Generally the groups were not differentiated on these measures on the Rorschach. The role-playing test showed greater discriminatory power than the Rorschach, possibly due to its explicit demand to produce representations of humans in interaction. Results of the role-playing test showed differentiation and integration scores were negatively correlated with measures of psychotic symptoms. Non-paranoids differed from the other three groups on differentiation measures, and paranoid and normal groups scored higher on integration measures than did the intermediate and nonparanoid groups. Paranoid subjects scored higher than nonparanoids on functional articulation and higher than intermediates on perceptual articulation; however, paranoid subjects were not differentiated from normals on any developmental measure. Differences between the schizophrenic sample and normals were explained entirely by the non-paranoid subgroup, supporting the paranoid-nonparanoid distinction and raising questions regarding the nature of the deficit in paranoid schizophrenia.

Adult↗