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Biomedical subjects

J G Johnson

Publications and source records attributed to J G Johnson.

At least 55 records · Page 3Linked to original sources
PubMed1996

Flow cytometric technique for quantitating cytotoxic response to photodynamic therapy.

A simple flow cytometric technique for rapid measurement of multilog cytotoxic responses to photosensitization of cellular systems is described. This technique is particularly useful for cell lines with a low colony-forming efficiency, for which a nonclonogenic assay is required. The assay separates cell-sized objects from cellular debris by gating on forward scatter versus side scatter, identifies viable cells by positive calcein AM and negative ethidium homodimer-1 staining and measures cell concentration relative to an internal standard of polystyrene beads. Large numbers of cells can be analyzed rapidly. Two patient-derived small cell lung cancer cell lines, NCI-H209 and SV-E, were used to test the technique. Photordiation survival curves of the response of these cell lines to 5-aminolevulinic acid-induced protoprophyrin IX photosensitization correlated with the extent of photosensitizer accumulation. There was good agreement between the results obtained using the tritiated thymidine incorporation assay and the flow cytometric cytotoxicity assay. The technique can be used to measure cytotoxic responses to photosensitization of cell lines regardless of their plating efficiencies.

Aminolevulinic Acid↗
PubMed1995

Psychiatric comorbidity, health status, and functional impairment associated with alcohol abuse and dependence in primary care patients: findings of the PRIME MD-1000 study.

The psychiatric comorbidity, health, and functioning of primary care patients with alcohol abuse and dependence (AAD) were investigated in a sample of 1,000 patients. Psychiatric symptomatology was assessed with the Primary Care Evaluation of Mental Disorders (PRIME-MD) diagnostic system. Health and functional status was assessed with the Medical Outcomes Study Short Form General Health Survey (SF-20). Results indicated that use of the PRIME-MD system brought about a 71% increase in physician recognition of AAD. AAD patients were diagnosed with substantial psychiatric comorbidity, and they reported poorer health and functioning than did patients without any psychiatric disorders. However, they reported less impairment and psychiatric comorbidity than did patients with other psychiatric disorders. Results also indicated that AAD patients' health and functioning were associated with the presence or absence of psychiatric comorbidity.

Adolescent↗
PubMed1995

Axis I psychiatric symptoms associated with HIV infection and personality disorder.

OBJECTIVE: The prevalences of personality disorders among HIV-positive and HIV-negative homosexual men were compared, and the presence of personality disorders was related to axis I psychiatric disorders, psychiatric distress, and impaired functioning. METHOD: The subjects were 162 homosexual men who either were HIV seronegative (N = 52) or were seropositive and had absent to moderate physical symptoms (N = 110). Lifetime and current histories of DSM-III-R axis I disorders, current diagnoses of DSM-III-R personality disorders, and levels of anxiety, depression, hopelessness, and adaptive functioning were assessed. RESULTS: In both the seropositive and seronegative groups, 19% of the study participants were diagnosed with personality disorders. The seropositive participants with personality disorders reported higher levels of psychiatric symptoms and poorer functioning than all participants without personality disorders, and they were over six times as likely as the seronegative participants without personality disorders to have current axis I disorders. CONCLUSIONS: These findings indicate that HIV infection and personality disorders may interactively increase the likelihood of clinically significant psychiatric symptoms.

Anxiety Disorders↗
PubMed1994

Utility of a new procedure for diagnosing mental disorders in primary care. The PRIME-MD 1000 study.

OBJECTIVE: To assess the validity and utility of PRIME-MD (Primary Care Evaluation of Mental Disorders), a new rapid procedure for diagnosing mental disorders by primary care physicians. DESIGN: Survey; criterion standard. SETTING: Four primary care clinics. SUBJECTS: A total of 1000 adult patients (369 selected by convenience and 631 selected by site-specific methods to avoid sampling bias) assessed by 31 primary care physicians. MAIN OUTCOME MEASURES: PRIME-MD diagnoses, independent diagnoses made by mental health professionals, functional status measures (Short-Form General Health Survey), disability days, health care utilization, and treatment/referral decisions. RESULTS: Twenty-six percent of the patients had a PRIME-MD diagnosis that met full criteria for a specific disorder according to the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition. The average time required of the primary care physician to complete the PRIME-MD evaluation was 8.4 minutes. There was good agreement between PRIME-MD diagnoses and those of independent mental health professionals (for the diagnosis of any PRIME-MD disorder, kappa = 0.71; overall accuracy rate = 88%). Patients with PRIME-MD diagnoses had lower functioning, more disability days, and higher rates of health care utilization than did patients without PRIME-MD diagnoses (for all measures, P < .005). Nearly half (48%) of 287 patients with a PRIME-MD diagnosis who were somewhat or fairly well-known to their physicians had not been recognized to have that diagnosis before the PRIME-MD evaluation. A new treatment or referral was initiated for 62% of the 125 patients with a PRIME-MD diagnosis who were not already being treated. CONCLUSION: PRIME-MD appears to be a useful tool for identifying mental disorders in primary care practice and research.

Adult↗
PubMed1994

Monocytes provide a novel costimulatory signal to T cells that is not mediated by the CD28/B7 interaction.

Resting CD4+T cells must receive nonspecific costimulatory signals from APC to produce maximal amounts of IL-2 in response to TCR signaling. The T cell-specific surface molecule CD28 is one protein that transduces a costimulatory signal following interaction with its ligand B7. We report here the identification of another contact-mediated costimulatory signal provided by the human histiocytic line U937 and by purified monocytes. Although this monocyte-derived costimulus is not transduced by the CD28/B7 interaction, it synergizes with the CD28 signal to elicit maximal IL-2 production from freshly isolated T cells. IL-2 production by previously activated CD8+ T cells depends on the monocyte-derived costimulatory signal, although memory CD4+ T cells respond well to either the monocyte-derived costimulus or B7-derived costimulation. In contrast, IL-2 secretion by naive T cells appears to require the synergistic interaction between both costimulatory pathways. These results suggest that the array of costimulatory ligands expressed by various APC affects the magnitude of the T cell response and also which T cell subsets are stimulated.

B7-1 Antigen↗
PubMed1994

The role of anergy in peripheral T cell unresponsiveness.

When a T cell's encounter with specific antigen results in good signaling through the T cell antigen receptor yet does not lead to a proliferative response, the T cell enters a state of nonresponsiveness, or anergy. Anergy induction can result from a number of different situations, including antigen presentation by costimulation-deficient or "non-professional" antigen presenting cells, pharmacological blocking of T cell proliferation, or chronic stimulation of the T cell receptor by antigen. Anergy is a long-lived but temporary state characterized by a profound inability of the T cell to produce IL-2. Other effector functions may be affected to variable degrees. Anergy has been characterized most carefully under in vitro conditions, but several experimental models have demonstrated that T cells can also become anergic in vivo. This mechanism for tolerance induction may help to ensure that any mature autoreactive T cells which escape thymic deletion are unable to respond to host tissues. Furthermore, an understanding of the mechanism of anergy induction will most certainly lead to beneficial clinical applications, including improving graft acceptance and avoiding such deleterious immune responses as autoimmunity and allergy.

Animals↗
PubMed1993

Accessory cell-derived signals required for T cell activation.

Various populations of accessory cells differ in their abilities to function as effective antigen-presenting cells (APC) and stimulate CD4+ T cells to produce interleukin-2. Three important factors directly related to APC potency are the expression of class II major histocompatibility complex molecules and the ability to present peptide antigens to the T cell antigen receptor, the expression of costimulatory ligands which deliver important activation signals independent of T cell receptor occupancy and the expression of adhesion molecules which promote conjugate formation so that these activation signals can be effectively delivered to the T cells. The relative importance of these accessory cell functions in T cell activation will be discussed, with an emphasis on costimulation and the CD28/B7 receptor/ligand pair. The consequence of inadequate costimulation by an otherwise effective APC in inducing T cell anergy will also be discussed.

Animals↗
PubMed1993

Molecules involved in T-cell costimulation.

Maximal expression of the interleukin-2 gene in T cells depends on biochemical signals in addition to those transduced by the T cell antigen receptor. Recent work indicates that the T-cell specific molecule CD28 transduces a 'costimulatory' signal when it binds its ligand, the B7 molecule, on the surface of an antigen-presenting cell. Results from experiments performed during the past year have raised the exciting possibility that immune responses can be either inhibited or augmented by manipulation of the CD28-B7 interaction.

Animals↗
PubMed1993

Preventable perioperative mortality from colorectal cancer.

Of 271 patients with primary colorectal cancer, 70 (26%) had detectable hepatic metastases. A primary tumour resection was possible for 225 (83%) of patients overall. Of the 46 patients with non resectable tumours, 38 (82%) had hepatic metastases. 23 (33%) of the patients with Dukes' D tumours died perioperatively relative to 13 (6%) of those with localised tumours (p < .001). Seventeen (70%) of the twenty three patients with Dukes' D cancers who died perioperatively had locally advanced disease but were not obstructed and had neither a resection or a stoma performed. Perioperative mortality is unacceptably high in patients with hepatic metastases but may be reduced by more specialised investigation of patients with suspected advanced disease to assess the degree of local dissemination and liver seeding prior to considering laparotomy.

Aged↗
PubMed1992

Tolerance induction in resting memory B cells specific for a protein antigen.

Resting memory B lymphocytes specific for the model protein Ag cytochrome c have been shown to be susceptible to tolerance induction in in vitro splenic fragment cultures. This induction of nonresponsiveness is dependent upon the strength of the interaction between surface Ig and specific Ag, where concentration, valency, affinity, and time of exposure all appear to be important factors, as is the case for tolerance induction in immature or primary B cells. The induction of nonresponsivenes in greater than 80% of Ag-specific memory B cells was achieved by incubation with 1 microM cytochrome polymer for 24 h in the absence of T cell help. Not only were memory B cells unresponsive to specific Ag, they were also unable to become activated through nonspecific uptake and presentation of an Ag to which T cells have been primed, demonstrating that the induction of nonresponsiveness involves more than a modulation or blockade of surface Ig receptors. Although soluble factors collected from activated T cells failed to prevent memory B cells from becoming nonresponsive after surface Ig cross-linking, the direct activation of T cells within splenic fragment cultures did partially inhibit tolerance induction in splenic fragment memory B cells. In addition, the induction of tolerance was partially blocked by protein tyrosine kinase inhibitors, suggesting a physiologic change within the B cells associated with the state of nonresponsiveness and resulting from tyrosine-specific phosphorylation.

Animals↗
PubMed1992

Life event categories differentially predict psychopathology symptom levels.

The present study used a prospective design to investigate whether eight categories of daily negative life events or "hassles" differentially predict psychopathology levels, and/or changes in psychopathology levels over 1 month in a mixed-sex, nonclinical sample of undergraduate subjects. Hassles were assessed using the Revised Hassles Scale (HS-R; DeLongis, 1985); psychopathology was assessed using the Hopkins Symptom Checklist (SCL-90; Derogatis, Lipman, & Covi, 1973) on two occasions, separated by 1 month. Scores on all eight HS-R subscales predicted Time 2 scores on most or all of the SCL-90 psychopathology scales. However, the magnitudes of these correlations varied widely, indicating that these subscales may be substantially different in their abilities to predict psychopathology levels.

Female↗
PubMed1992

Co-stimulatory functions of antigen-presenting cells.

Antigen-presenting cells, in addition to presenting processed antigen, provide co-stimulatory signals that are necessary for stimulating maximal lymphokine production by CD4+ T cells. For interleukin 2 (IL-2)-producing CD4+ T cells, the B7 molecule provides an important co-stimulatory signal through interaction with its ligand on the T-cell surface, CD28. Populations of antigen-presenting cells that express high levels of B7 (e.g., dendritic cells) are much more potent stimulators of T-cell activation than cells that fail to express B7 (e.g., resting B cells). An increase in B7 expression could therefore explain the increased accessory function gained by Langerhans cells as they leave the skin and migrate to the draining lymph node.

Antigen-Presenting Cells↗
PubMed1992

Aminoglycosides, imipenem, and aztreonam.

The aminoglycosides continue to be the cornerstone of antibiotic therapy for serious infections caused by gram-negative aerobic pathogens, even with the recent introduction of potent beta-lactams and the fluoroquinolones. Two of these newer agents are imipenem and aztreonam. Imipenem is the most expensive commercially available antibiotic, but it has the broadest range of activity, including most gram-negative and gram-positive, aerobic and anaerobic bacteria. Aztreonam, the first monobactam antibiotic to be released, has excellent activity against aerobic, gram-negative bacteria. It is not, however, simply a nonnephrotoxic replacement for aminoglycoside therapy. This article reviews the basic pharmacology and clinical utility of the aminoglycosides, imipenem, and aztreonam.

Aminoglycosides↗
PubMed1991

Different functional boundaries for the major antigenic region of two cytochromes c.

The antigenic sites of horse and rat cytochromes c in the major antigenic region were compared using a panel of variant cytochromes c and a large number of BALB/c mouse monoclonal antibodies (mAbs) in competitive ELISAs. The major antigenic region of cytochrome c is located on the surface opposite of that containing the exposed heme crevice. mAbs specific for this region on rat cytochrome c were affected in binding by amino acid substitutions at positions 62 and at one or more of positions 3, 100, 103, and 104 but not by a substitution at position 89. In contrast, mAbs specific for the same region on horse cytochrome c were affected by amino acid substitutions at positions 62, (probably) 60, and 89. Some, but not all, of the anti-horse cytochrome c mAbs were affected by amino acid substitutions at one or more of positions 3, 100, 103, and 104. Thus, the functional boundaries of this antigenic region are different for these two cytochromes c, as shown primarily by the differential effects of residue 89. This distinction is most likely due to one or more of the four amino acid differences between horse and rat cytochromes c on the antigenic surface that result in different physicochemical properties for the horse and rat proteins. The results suggest that as yet unidentified physicochemical parameters, possibly surface topography and/or charge distribution, influence the focusing of antibodies onto the surface of a protein antigen.

Amino Acid Sequence↗
PubMed1991

A monoclonal antibody specific for a cytochrome c T cell stimulatory peptide inhibits T cell responses and affects the way the peptide associates with antigen-presenting cells.

A monoclonal antibody (mAb) specific for the 93-104 segment of pigeon cytochrome c (cyt) was shown to block interleukin 2 production and proliferation by pigeon cyt-specific T cells in response to the pigeon cyt 81-104 peptide using either the LK35.2 B cell hybridoma or normal splenocytes as antigen-presenting cells (APC). The mAb inhibited the response to soluble peptide antigen presented by metabolically inactive paraformaldehyde-fixed APC but not the response to APC that were pre-pulsed with Ag. These results suggest that the mAb blocked the formation of peptide-major histocompatibility complex (MHC) class II molecule complexes at the cell surface but did not displace the peptide once bound to the MHC class II molecule. As determined by direct binding experiments using labeled peptide, the major means of free peptide association with live APC was fluid-phase endocytosis. No free peptide associated directly with the MHC class II molecule at the cell surface near 0 degrees C since APC pulsed with peptide on ice did not activate cyt-specific T cells. The mAb enhanced the association of the radiolabeled peptide with APC at 4 degrees C apparently by binding of the peptide-mAb complex to Fc receptors. By stripping molecules from the LK35.2 cell surface using a nonspecific protease it was shown that the peptide-mAb complexes were not internalized either at 4 degrees C or 37 degrees C. Since the mAb was found to stably bind the peptide at pH levels below that of endosomes (pH 5.5-6.2) even if the peptide-mAb complexes were taken up by fluid-phase endocytosis, it is likely that the peptide would not be able to associate with MHC class II molecules inside the APC. This mAb appears to inhibit T cell activation by blocking the formation of peptide-MHC class II molecule complexes at the cell surface and by interfering with uptake of the peptide into endosomes. Therefore, it is different from other antibodies that have been reported to block T cell receptor recognition of preformed peptide/MHC class II molecule complexes.

Animals↗
PubMed1991

Relative frequencies of secondary B cells activated by cognate vs. other mechanisms.

Three distinct mechanisms for the activation of secondary B cells to antibody-forming cells have been examined in splenic fragment cultures. The clonal response to a protein antigen [cytochrome c (cyt)] was quantified in terms of both the number of B cells activated and the amount of antibody produced by each clone. The vast majority of memory B cells required surface immunoglobulin (sIg) receptor-mediated uptake of antigen followed by cognate interactions with an antigen-specific T helper cell. Nevertheless, a significant number (as many as 12%) could be activated via soluble factor-mediated bystander activation, involving occupation of neither the sIg receptor nor class II major histocompatibility complex (MHC) molecules. This pathway, however, was relatively inefficient in that individual clones secreted less than half as much antibody as clones activated as a result of cognate collaboration with a T helper cell. A similar number of secondary B cells were activated following nonspecific uptake of high concentrations of antigen for which splenic fragment T cells had been primed [i.e., hemocyanin (Hy)], independent of sIg receptor occupancy. Antibody levels were similar to those in cultures where B cells were activated in a cognate manner with sIg receptor occupancy. When Hy-stimulated fragment cultures were supplemented with polymerized cyt, the frequency of activation via this latter pathway increased fourfold, despite the fact that no cyt-primed T cells were present. This observation supports the idea that receptor-mediated uptake of antigen serves not just to focus antigen but also provides an important signal in activating B cells. Bystander B cell activation, however, was not enhanced by providing a sIg cross-linking signal with polymerized cyt. The lower level of antibody production by B cells activated in a bystander fashion and the inability to enhance their frequency of activation with sIg receptor occupancy suggest that there is indeed a fundamental difference between soluble factor-mediated bystander activation and activation via T cell determinant-mediated cognate T helper-B cell interactions, perhaps involving signaling through class II MHC molecules.

Animals↗
PubMed1991

Differential growth inhibition and enhancement of major histocompatibility complex class I antigen expression by interferons in a small-cell lung cancer cell line and its doxorubicin-selected multidrug-resistant variant.

Expression of class I and class II major histocompatibility complex antigens on a human small-cell lung cancer cell line and its multidrug-resistant variant was examined before and after exposure to interferon alpha (IFN alpha) and IFN gamma by flow cytometry. Neither IFN alpha nor IFN gamma induced class II antigen expression on the drug-sensitive or resistant cell line. Induction of class I antigen expression along with an inhibition of proliferation was observed in both cell lines after IFN alpha treatment. On the other hand, IFN gamma treatment resulted in growth inhibition and enhancement of class I antigen expression in the sensitive cell line but not the resistant cell line. The differential response of the two cell lines to IFN gamma cannot be directly attributed to the acquisition of drug resistance but it suggests that further investigation of the possibility that drug-sensitive and resistant small-cell lung tumors may respond differently to immunotherapies that include IFN gamma is warranted.

Carcinoma, Small Cell↗