Search PubMed⌕ Search

Biomedical subjects

M J Dolan

Publications and source records attributed to M J Dolan.

52 records · Page 3Linked to original sources
PubMed1993

Restoration of HIV-specific cell-mediated immune responses by interleukin-12 in vitro.

Peripheral blood mononuclear cells (PBMCs) from many asymptomatic individuals infected with human immunodeficiency virus-type 1 (HIV) are unresponsive as measured by in vitro T cell proliferation and interleukin-2 (IL-2) production to influenza virus and synthetic peptides of HIV envelope (Env). Strong influenza virus- and Env-stimulated IL-2 responses and T cell proliferation were restored when cultures were stimulated in the presence of IL-12. Interferon-gamma production by PBMCs from HIV seropositive (HIV+) patients was also restored with IL-12. Furthermore, in vitro antigen-specific production of IL-2 and proliferation of PBMCs from HIV- donors were suppressed by antibody to IL-12, but were not enhanced by addition of exogenous IL-12. Thus, IL-12 may be limiting in PBMCs from HIV+ but not HIV- individuals. These findings demonstrate that IL-12 can restore HIV-specific cell-mediated immunity in vitro in HIV-infected individuals and suggest a potential use of IL-12 in augmenting the diminished immunologic functions associated with HIV infection.

Cells, Cultured↗
PubMed1993

Syndrome of Rochalimaea henselae adenitis suggesting cat scratch disease.

OBJECTIVE: To describe a clinical syndrome of cat scratch disease caused by Rochalimaea henselae, including methods for isolation of the organism from tissue and for identification. DESIGN: Case series. SETTING: U.S. Air Force referral hospital infectious diseases clinic. PATIENTS: Two previously healthy patients. MAIN MEASUREMENTS AND RESULTS: Two immunocompetent patients who had handled cats developed unilateral upper-extremity adenitis associated with a distal papular lesion and fever. The adenitis and distal lesions persisted and progressively worsened. Cultures of the involved lymph nodes from both patients grew R. henselae, a recently described organism associated with bacillary angiomatosis and peliosis hepatis in human immunodeficiency virus-infected patients and with bacteremia in immunocompromised and immunocompetent hosts. The organism was characterized as oxidase negative and X-factor dependent and had a characteristic pattern in analysis of whole-cell fatty acids differing from Afipia felis, a bacterium that has been associated with cat scratch disease. The identity of the isolate was confirmed by analysis of whole-cell fatty acids using gas chromatography and by amplification of the citrate synthetase gene sequence and analysis of the polymerase chain reaction-amplified product. The organisms were broadly susceptible to a variety of antimicrobials by broth microdilution; however in-vitro resistance to first-generation cephalosporins correlated with clinical failure of therapy. CONCLUSION: Rochalimaea henselae can be a cause of cat scratch disease in immunocompetent patients.

Adult↗
PubMed1993

Limiting dilution analysis of interleukin-2-producing T cells responsive to recall and alloantigens in human immunodeficiency virus-infected and uninfected individuals.

Peripheral blood mononuclear cells (PBMC) from individuals who were seropositive for the human immunodeficiency virus type 1 (HIV), and most without symptoms (HIV+) were compared with PBMC from healthy HIV-seronegative (HIV-) individuals for in vitro generated T helper cell (Th) responses. Th function in bulk culture and limiting dilution analysis was assessed by IL-2 production following stimulation with influenza A virus (FLU) or irradiated allogeneic PBMC (ALLO). We observed that the frequencies of FLU- and ALLO-stimulated Th cells were not appreciably different in the PBMC of HIV- individuals, and that they were also not different in the PBMC of those HIV+ individuals who responded to both FLU and ALLO in bulk culture. However, there was a severe drop in the Th frequency to FLU in HIV+ individuals who were unresponsive to FLU but responsive to ALLO by bulk culture. The PBMC of HIV+ individuals who were unresponsive by bulk culture to both FLU and ALLO exhibited a drastic reduction in the Th frequencies for both stimuli. These results demonstrate a concordance between Th functional analysis performed by limiting dilution and bulk culture. The results also indicate that the early selective loss in Th function to recall antigens is not likely to be due simply to a difference in frequencies of FLU- and ALLO-stimulated Th cells present prior to the onset of Th dysfunction.

Cell Line↗
PubMed1993

Early markers of HIV infection and subclinical disease progression.

Human immunodeficiency virus (HIV) infection in US Air Force personnel between 1985 and 1989 was examined through a mandatory serological survey, and through annual examination of infected patients. CD4+ cell counts were determined by flow cytometry; beta 2 microglobulin and neopterin were measured by immunoassay. During this period 933 cases were found, of which 161 were documented seroconversions, giving an incidence rate of 15.6/100,000 person-years. For patients with > 400 CD4 cells microliters-1, the rate of initial occurrence of opportunistic infection was 1 and 4% at 1 and 2 years, respectively. HIV-infected persons with < 400 CD4+ cells microliters-1, in contrast, had rates of 21% at 1 year and 36% at 2 years. In a cross-sectional study, beta 2 microglobulin concentration was shown to increase in both the serum and spinal fluid of patients infected with HIV as their blood CD4 numbers declined. Neopterin levels in serum and spinal fluid showed a similar trend, with significantly lower neopterin concentrations in the group that had > 1000 CD4+ T cells compared to the 0-600 CD4+ cell group. Longitudinal studies included correlation of HIV p24 antigen with CD4 counts over a 1 year period. The p24 antigen-positive group had a 21% decline in CD4+ T cells, while the antigen-negative group had a 14% decline. Specific helper T-cell subsets were also examined over a 6 month period. A significant decline was seen in the CD4+/CD29+, CD4+/CD45R+, and overall CD4+ subsets which was not seen in AZT-treated patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Aerospace Medicine↗
PubMed1993

Q fever meningoencephalitis in a soldier returning from the Persian Gulf War.

Acute infection with Coxiella burnetti usually results in a self-limited illness requiring a high index of clinical suspicion for diagnosis. Although headache is a common presentation of acute infection with this agent, focal neurological deficits are considered to be limited to chronic infection, most commonly caused by emboli from endocarditis. We report the case of a soldier returning from Desert Storm who presented with headache and a crescendo pattern of transient ischemic attacks and had serology consistent with an acute Q fever infection. The English-language literature on central nervous system infection caused by Coxiella burnetti is reviewed.

Antibodies, Bacterial↗
PubMed1993

Longitudinal analysis of the humoral immune response to human immunodeficiency virus type 1 (HIV-1) gp160 epitopes in rapidly progressing and nonprogressing HIV-1-infected subjects.

Antibody response to conserved human immunodeficiency virus type 1 (HIV-1)IIIB gp160 epitopes was longitudinally examined in HIV-1-infected persons. Twelve hundred individuals were evaluated, and sequential sera from 25 rapidly progressing (RP) and 30 nonprogressing (NP) subjects collected over an average of 4 years were examined. Initial sera from the RP group contained greater reactivity to a gp120 epitope defined by peptide 503-528 than did sera from the NP group (P < .001). Reactivity declined with sequential sera for the RP group, paralleling disease progression. Conversely, antibody recognition to this site developed in 23% of the NP group with time. However, 60% of the NP group never developed a response to this epitope. This suggests sequential examination of antibody response to an epitope within the gp120 carboxyl-terminus may have prognostic significance. No association between antibodies directed against the gp160 epitopes and in vitro neutralizing activity against HIV-1IIIB was observed.

Adult↗
PubMed1993

Production of a murine monoclonal antibody that recognizes an epitope specific to Coccidioides immitis antigen 2.

Antigen 2 (Ag2) has been implicated as a T-cell-reactive component of the pathogenic fungus Coccidioides immitis. We report the production of a murine monoclonal antibody (MAb) of the immunoglobulin G2a isotype that recognizes an epitope specific to C. immitis Ag2. This specificity was evidenced by the finding that the MAb did not recognize other antigens present in coccidioidin or spherulin and did not show reactivity with antigenic extracts from Histoplasma capsulatum or Blastomyces dermatitidis. The epitope was labile to enzymatic digestion with pronase but resistant to treatment with glycolytic enzymes and to periodate oxidation. This peptide epitope appears to require conformational structure on the basis that it was not recognized by the MAb in immunoblots of antigen that had been electrophoresed in polyacrylamide gels under denaturing, reducing conditions. Immunoaffinity chromatography of spherulin on columns containing the MAb established that the MAb was effective as a ligand for isolating Ag2 from heterogeneous extracts. The production of a MAb which recognizes an Ag2-specific epitope and its utility as a ligand for isolating Ag2 will provide a valuable reagent for studies of this immunologically important antigen.

Animals↗
PubMed1992

Coccidioides immitis presenting as a mycelial pathogen with empyema and hydropneumothorax.

A previously healthy Caucasian male developed hydropneumothorax and a pleural peel filled with pleomorphic, septate hyphae. The only organism grown from cultures of the lung and pleural fluid was Coccidioides immitis, confirmed by exoantigen testing. Spherule-endospore forms were produced, however, following injection of the arthroconidial tissue isolate into BALB/c mice. The patient had a positive immunodiffusion complement-fixation test and developed a positive coccidioidin skin test during therapy. He recovered following thoracotomy and wedge resection of the ruptured coccidioidal cavity, and therapy with amphotericin B followed by fluconazole. The sole presence of the mycelial form of the dimorphic fungus C. immitis in the pleural space may have been due to a low CO2 partial pressure at that site secondary to a bronchopleural fistula. The case shows a distinctive and uncommon presentation of coccidioidomycosis which demonstrates the specificity of both the immunodiffusion complement-fixation assay in diagnosing this disease and the exoantigen test in confirming culture results.

Animals↗
PubMed1992

Significant infections due to Bacillus species following abrasions associated with motor vehicle-related trauma.

Non-anthracis Bacillus species are ubiquitous gram-positive spore-forming organisms that were once believed to be nonpathogenic but are now recognized as causing a variety of infections. We report a new aspect of trauma associated with bacillus infection: clinically significant infection by Bacillus species in patients who are involved in motor vehicle accidents and sustain injury related to road contact. Cases were evaluated retrospectively from May 1990 through December 1991. Four patients who had documented infections with Bacillus species and who were involved in motor vehicle accidents associated with road trauma were identified during this period. The antibiotic susceptibility profile of the Bacillus species consistently demonstrated resistance to beta-lactam antibiotics. This series of cases illustrates an additional aspect of disease associated with bacteria of the Bacillus species that should be considered for patients who have sustained injuries from motor vehicle accidents associated with road trauma.

Accidents, Traffic↗
PubMed1992

Relapsing illness due to Rochalimaea henselae in immunocompetent hosts: implication for therapy and new epidemiological associations.

Two previously healthy, immunocompetent men had persistent Rochalimaea henselae bacteremia with clinical relapses after courses of antibiotics to which the isolates were ultimately demonstrated susceptible in vitro. Both had sustained tick bites prior to their illnesses, thus demonstrating an association not previously identified, although suspected. The first patient had relapsing fever, constitutional symptoms, and an episode of aseptic meningitis despite therapy with amoxicillin, then with doxycycline, and then with ceftriaxone. Thereafter, he spontaneously became asymptomatic during a span of 2 months of persistent bacteremia. Finally, after 2 weeks of therapy with ceftriaxone plus gentamicin, followed by 4 weeks of therapy with oral ciprofloxacin, his bacteremia was cured. The second man had relapsing fever and constitutional symptoms after courses of tetracycline, then of chloramphenicol, and then of doxycycline. He became permanently asymptomatic after serial 2-week courses of chloramphenicol and erythromycin. The greater efficacy of lysis-centrifugation blood cultures in the recovery of R. henselae was noted.

Adult↗
PubMed1992

Localization of the tube precipitin and complement fixation antigens of Coccidioides immitis by immunoelectron microscopy with murine monoclonal antibodies.

The cellular localization of the tube precipitin (TP) and complement fixation (CF) antigens of Coccidioides immitis was examined by immunoelectron microscopy with murine immunoglobulin G1 monoclonal antibodies directed against the TP and CF antigens, respectively. Immunoelectron microscopic analyses of saprobic- and parasitic-phase cells showed that the TP antigen is present at a high concentration within the inner cell wall layer and along the plasma membrane. The antigen was also detected, at a lesser concentration, within cytoplasmic vacuoles. In contrast to the predominant localization of the TP antigen in the cell walls, the CF antigen residues primarily within the cytoplasm, where it appears to be dispersed throughout the cytoplasm rather than associated with a specific cytoplasmic organelle. A sparse amount of the CF antigen within the inner cell walls was also demonstrable. The localization of the TP and CF antigens throughout the morphogenetic phases of C. immitis has important implications in antigen production and in analyses of host response in coccidioidomycosis.

Animals↗
PubMed1991

Production and characterization of a monoclonal antibody to the complement fixation antigen of Coccidioides immitis.

Detection of complement-fixing antibody to coccidioidin by using the complement fixation test or an immunodiffusion assay for complement-fixing antibody (IDCF) is widely viewed as the most useful immunodiagnostic test for coccidioidomycosis. In this investigation, we report the production of an immunoglobulin G subclass 1 (IgG1) monoclonal antibody (MAb) to the IDCF antigen for use as a biospecific ligand for purifying the IDCF antigen on solid-phase immunosorbents and for use as a reagent for screening genomic or cDNA expression libraries from Coccidioides immitis. BALB/c mice were immunized by intramuscular injections of coccidioidin in adjuvant, followed by an intrasplenic booster injection of coccidioidin in saline. The spleen cells were fused with SP2/0 Ag14 myeloma cells, and the fusion products were screened for IgG antibody to coccidiodin by using an enzyme-linked immunosorbent assay. Positive hybridomas were cloned and evaluated for reactivity to the IDCF antigen by two-dimensional immunoelectrophoresis and by immunoblotting. An IgG1 Mab was produced that was specific for the IDCF antigen when evaluated by two-dimensional immunoelectrophoresis and immunoblotting. The epitope recognized by the MAb was heat labile (60 degrees C, 30 min) and susceptible to enzymatic digestion with pronase but was resistant to treatment with lipase, alpha-mannosidase, glucose oxidase, and endoglycosidase H. This heat-labile peptide epitope appears to be specific to C. immitis, as judged by the fact that the MAb was not reactive in immunoblots or enzyme-linked immunosorbent assays of histoplasmin or blastomycin.

Animals↗
PubMed1989

Development and characterization of a monoclonal antibody against the tube precipitin antigen of Coccidioides immitis.

Primary infection with Coccidioides immitis is commonly accompanied by the production of an immunoglobulin M precipitin antibody which is detected by the tube precipitin (TP) assay or by the immunodiffusion assay for TP antibody (IDTP assay). In the present investigation, spleen cells from spherulin-immunized BALB/c mice were fused with SP2/O Ag14 myeloma cells, and the resulting hybridomas were screened for antibody to the IDTP antigen by using an enzyme-linked immunosorbent assay. Positive hybridomas were cloned by limiting dilution and injected into pristane-primed mice for ascites production. Characterization of antibody reactivity was accomplished with the IDTP assay, two-dimensional immunoelectrophoresis, and immunoblotting. An immunoglobulin G1 monoclonal antibody which reacts with the IDTP antigen of C. immitis is described. The epitope that is recognized by the monoclonal antibody is also present, but to a lesser extent, on a second coccidioidal antigen which has been designated antigen 2. The monoclonal antibody was not reactive in immunoblots of histoplasmin or blastomycin, indicating that the epitope recognized by this antibody may be specific for C. immitis.

Animals↗
PubMed1982

Pathogenesis of dialysis-induced hypoxemia.

Patients undergoing hemodialysis with acetate-containing dialysis solutions develop hypoxemia. To determine the cause of the hypoxemia, we studied and compared the ventilatory, gas-exchange and blood-gas responses in chronic renal failure patients undergoing hemodialysis with acetate and bicarbonate dialysis solutions. Seven stable chronic dialysis patients were dialyzed against acetate and bicarbonate solutions in a random order. Dialysis was carried out using a 1.5 m2 hollow fiber dialyzer at a blood flow rate of 200 ml/min and a dialysate flow rate of 500 ml/min. During acetate dialysis, PaO2 fell within 15 minutes from a mean control predialysis concentration of 84 = 6 (SEM) mmHg to a mean of 70 +/- 7.5 mmHg (P less than 0.05), and remained low throughout the study. PaO2 did not change significantly during bicarbonate dialysis. Total ventilation fell from a predialysis level of 7.2 +/- 0.7 L/min to 5.7 +/- 0.6 L/min within 15 minutes (P less than 0.05). PaCO2 was not significantly changed from predialysis levels with either acetate or bicarbonate dialysis. Measurement of blood concentration of CO2 and bicarbonate across the dialyzer indicated that the total CO2 loss (as CO2 and bicarbonate) through the dialyzer was 3 millimoles per minute or the equivalent of approximately 60 ml of CO2 per minute, i.e., about one third of the patient's metabolic production of CO2.

Acetates↗
PubMedDate not supplied

Near-drowning-associated Aeromonas pneumonia.

Aeromonas is increasingly recognized as a human pathogen that causes a variety of different infections. Aeromonas has rarely been reported as a cause of respiratory infection, and it has been described in near-drowning-associated pneumonia. This article reviews a case of Aeromonas sobria pneumonia associated with a near drowning and considers the clinical and epidemiological characteristics of 10 previously reported cases. Nearly all of the cases involved young healthy men, a rapid development of pneumonia and sepsis after a brief stable period postimmersion, and bilateral infiltrates on chest radiography. A very high rate of positive blood cultures and mortality was also noted. The epidemiological and clinical data in this review may be helpful to the clinician caring for near-drowning victims. Although prophylactic antibiotics are not recommended for near-drowning victims, broad-spectrum antibiotics should be rapidly instituted with any evidence of infection.

Adolescent↗