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Biomedical subjects

L L Johnson

Publications and source records attributed to L L Johnson.

At least 109 records · Page 6Linked to original sources
PubMed1991

Evidence against suppressor cell involvement in naturally acquired tolerance of a minor histocompatibility antigen.

The hypothesis was investigated that suppressor cells may be responsible for maintenance of immunologic tolerance of a minor H3 antigen in mice that express the antigen naturally. Lymphoid cell populations from B6.C-H-24c (HW54) mice, a congenic-resistant strain histoincompatible with H-24b-expressing C57BL/6 (B6) mice only with respect to the H-24 locus, were examined in cell-transfer experiments to see if they contained naturally arising H-24c-specific suppressor cells. The H-24 antigen was chosen for these studies because, unlike most other minor and major histocompatibility (H) antigens, it is not detectable on mature lymphoid cells by any of several functional criteria. Thus transfer of HW54 lymphoid cells to B6 hosts could be done without the complication of inducing hyporesponsiveness de novo in the host, as occurs with other minor H antigens that are expressed on lymphocytes. B6 hosts were given HW54 skin grafts along with HW54 lymphoid cells to assess their tolerance of the H-24c-encoded antigen. The hosts were either (1) normal, nonimmune B6 mice; (2) B6 mice rendered immunodeficient by thymectomy and irradiation (TXB) and repopulated with H-24c-immune B6 lymphocytes; or (3) TXB B6 hosts repopulated with nonimmune B6 lymphocytes. In each case it was found that the additionally infused HW54 lymphoid cells did not suppress the ability of these hosts to reject HW54 skin grafts. In other words, HW54 lymphoid cells appear not to possess suppressive activity specific for the H-24c antigen that might maintain antigen-specific natural tolerance. Additional experiments were performed to determine whether HW54 lymphoid cells can inhibit the ability of sublethally irradiated B6 mice to regain the capacity to reject HW54 skin. The purpose of these experiments was to determine whether there are naturally occurring HW54 lymphoid cells that can suppress the development of lymphocytes potentially reactive to H-24c antigen that presumably emerge in B6 mice following sublethal irradiation. Such suppressor cells would be candidate initiators of self-tolerance. Here, too, no evidence for such suppressor cells was obtained.

Animals↗
PubMed1991

Synergistic activity of 5-trifluoromethylthioribose and inhibitors of methionine synthesis against Klebsiella pneumoniae.

5-Methylthioribose (MTR) is an intermediate in the methionine recycling pathway of organisms containing the enzyme MTR kinase. Analogs of MTR have been proposed as a new class of antimicrobial agents because of their ability to perturb the growth of MTR kinase-containing pathogens through inhibition of methionine salvage or by conversion to toxic products. One such analog, 5-trifluoromethylthioribose (TFMTR), has demonstrated potent inhibitory effects on the growth of Klebsiella pneumoniae (A. G. Gianotti, P. A. Tower, J. H. Sheley, P. A. Conte, C. Spiro, J. H. Fitchen, and M. K. Riscoe, J. Biol. Chem. 265:831-837, 1990). Although the mode of action of TFMTR has yet to be determined, it is believed that the drug is converted to the toxic products trifluoromethionine or carbonothioic difluoride via MTR kinase and the methionine recycling pathway. On the basis of this assumption, we theorized that blocking de novo methionine synthesis would increase dependence on the methionine salvage pathway and lead to an increased rate of synthesis of toxic metabolites from TFMTR. In this report, we show that three separate inhibitors of de novo methionine synthesis (1,2,4-triazole, azaserine, and propargylglycine) act synergistically with TFMTR in inhibiting the growth of K. pneumoniae.

Alkynes↗
PubMed1991

A review of cardiac imaging with sestamibi and teboroxime.

Overall, it is clear that the two new technetium-labeled compounds can provide diagnostic myocardial perfusion imaging both at stress (exercise and pharmacologic) and rest, but they have very different mechanisms of transport in comparison to each other and to thallium. Therefore, new imaging protocols will need to be developed and refined by practical experience as the use of these agents expands. Further investigative work needs to be done to optimize protocols and computer processing of images. In addition, special clinical situations will become associated with the use of these new compounds. Nuclear cardiology will continue to advance during this time of great changes and challenges if informational exchange on these topics continues to flourish and critical clinical trials are completed.

Coronary Disease↗
PubMed1991

Antimyosin imaging in cardiac transplant rejection.

Fab fragments of antibodies specific for cardiac myosin have been labeled with indium-111 and injected intravenously into animals and into patients with heart transplants. The antibodies, developed by Khaw, Haber, and co-workers, localize in cardiac myocytes that have been damaged irreversibly by ischemia, myocarditis, or the rejection process. After clearance of the labeled antibody from the cardiac blood pool, planar imaging or single photon emission computed tomography is performed. Scintigrams reveal the uptake of the labeled antimyosin in areas of myocardium undergoing transplant rejection. In animal studies, the degree of antimyosin uptake appears to correlate significantly with the degree of rejection assessed at necropsy. In patients, the correlation between scans and pathologic findings from endomyocardial biopsy is not as good, possibly because of sampling error in the endomyocardial biopsy technique. The scan results at 1 year correlate with either late complications (positive) or benign course (negative). Current limitations of the method include slow blood clearance, long half-life of indium-111, and hepatic uptake. Overcoming these limitations represents a direction for current research. It is possible that from these efforts a noninvasive approach to the diagnosis and evaluation of cardiac transplantation may evolve that will decrease the number of endomyocardial biopsies required to evaluate rejection. This would be particularly useful in infants and children.

Animals↗
PubMed1991

Failure of a tumour to prime CTL specific for some of the minor H antigens it expresses but not others.

The H-Y-expressing murine tumour, ET-5, specifically immunizes B6 female mice that have rejected it against H-Y-positive male skin grafts, yet fails to prime their spleen cells for the generation of H-Y-specific cytotoxic T lymphocytes (CTL). ET-5 also fails to prime relevant congenic hosts to generate CTL specific for H-3 or H-25 minor H antigens, or major histocompatibility complex (MHC) class I antigens, all of which are expressed in immunogenic form by ET-5. Nonetheless, C3H.SW mice, which are MHC-compatible with B6 mice in which ET-5 originated, but differ from B6 at many minor H loci, can be primed to generate CTL directed against one or more unidentified minor H antigens. These CTL are conventional MHC-restricted, CD8+ T cells, and require priming in vivo for their generation. Significantly, C3H.SW females can be primed by ET-5 to generate B6-specific CTL, but not H-Y-specific CTL. Thus CTL priming is selective in the sense that ET-5 primes CTL specific for some of the antigens it expresses but not others. The basis for this selectivity is not known but, in the case of H-Y antigen, it appears not to result from an inability of ET-5 to express either H-2Db-encoded antigens, the restriction element for H-Y-specific CTL in B6 females, or H-Y itself in vivo.

Animals↗
PubMed1990

Clinical experience with technetium-99m teboroxime, a neutral, lipophilic myocardial perfusion imaging agent.

Technetium-99m (Tc-99m) teboroxime is a new technetium-based myocardial perfusion imaging agent (investigational code = SQ30217 [Cardiotec, Squibb Diagnostics]). A member of a class of neutral, lipophilic, technetium-containing complexes known as boronic acid adducts of technetium dioxime (BATO) complexes, this agent is chemically very different from the cationic tracer thallium-201 (Tl-201) and from the cationic technetium complex Tc-99m sestamibi (Cardiolite, Du Pont Imaging Agents). Tc-99m teboroxime has high myocardial extraction, rapid blood clearance, little lung uptake and rapid myocardial washout. A biexponential pattern of myocardial washout is demonstrated in animals and in man. Effective half-lives of the 2 washout components in man are 5.2 minutes and 3.8 hours and represent approximately 66 and 33% of the myocardial activity, respectively. The first half-life for the myocardium is approximately 11 minutes. As the agent washes out of the heart, hepatic uptake occurs, peaking at about 5 minutes after injection. The liver is the major organ of excretion and receives, along with the large bowel, the largest radiation dose. Rapid imaging protocols using standard cameras have achieved good myocardial counts from 3 planar views acquired over a 4- to 5-minute period or for single photon emission computed tomography (SPECT) images acquired over a 10-minute period. An entire stress/rest procedure can be completed in 1 hour. Analysis of data from 155 patients from 4 centers using planar or SPECT imaging showed a sensitivity and specificity for blinded readings of 82 and 91%, respectively, when compared against overall clinical impression.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Disease↗
PubMed1990

Overview of studies on liver carcinogenesis in English sole from Puget Sound; evidence for a xenobiotic chemical etiology. I: Pathology and epizootiology.

Livers of wild English sole (Parophrys vetulus) from polluted waterways and embayments of Puget Sound, Washington, are affected by a spectrum of multiple, co-occurring idiopathic hepatic lesions, including neoplasms, putative preneoplastic foci of cellular alteration, and unique degeneration conditions. Results from a statistical analysis of the patterns of co-occurrence of these lesions in wild English sole indicate that these lesions represent morphologically identifiable steps leading to the development of hepatic neoplasms. This sequence parallels the lesion progression in experimental models of chemically induced liver carcinogenesis in rodents. The hypothesis that these lesions in wild English sole can be caused by exposure to certain xenobiotic hepatotoxic and hepatocarcinogenic compounds in Puget Sound is based on: a) statistical associations between levels of aromatic hydrocarbons (sigma AHs) in sediment and prevalences of these idiopathic liver lesions, b) the contribution of sigma AHs in accounting for the variability in hepatic neoplasm prevalence in a logistic regression model, c) elevated odds ratios for several idiopathic hepatic lesion types in sole from polluted sites in Puget Sound, d) significant correlations between prevalences of idiopathic hepatic lesions and levels of fluorescent metabolites of aromatic compounds (FACs) in bile of English sole, and e) experimental induction of putatively preneoplastic focal lesions in English sole injected with a PAH-enriched fraction of an extract from a contaminated urban sediment from Puget Sound, that were morphologically identical to lesions found in wild English sole from the same site.

Animals↗
PubMed1990

Prognostic significance of silent myocardial ischemia on a thallium stress test.

The clinical significance of silent ischemia is not fully known. The purpose of this study was to determine whether the presence or absence of angina during a thallium stress test positive for ischemia was independently predictive of an adverse outcome. Two hundred thirty-four consecutive patients with ischemia on a thallium stress test were identified. Ischemia was defined as the presence of defect(s) on the immediate postexercise scans not in the distribution of prior infarctions that redistributed on 4-hour scans. During the test 129 patients had angina, defined as characteristic neck, jaw, arm, back or chest discomfort, while the remaining 105 patients had no angina. Follow-up ranged from 2 to 8.2 years (mean 5.2 +/- 2.1) and was successfully obtained in 156 patients. Eighty-two of the 156 patients had angina (group A) and 74 had silent ischemia (group S). Group A patients were significantly older (62 +/- 8 vs 59 +/- 8 years, p less than 0.05). There was no significant difference between the 2 groups in terms of sex, history of prior infarction or presence of left main/3-vessel disease. A larger percentage of patients in group A were receiving beta blockers (60 vs 41%, p less than 0.05) and nitrates (52 vs 36%, 0.05 less than p less than 0.10). There was a large number of cardiac events (myocardial infarction, revascularization and death) in both groups (37 of 82 [45%] in group A; 28 of 72 [38%] in group S) but no statistically significant difference between the groups. Similarly, life-table analysis revealed no difference in mortality between the 2 groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗
PubMed1990

Osteochondritis dissecans of the knee: arthroscopic compression screw fixation.

This article describes repair of osteochondritis dissecans of the knee by arthroscopic compression screw fixation and reports the healing response and clinical result. Diagnostic and operative arthroscopy was performed. Compression screw fixation was used. The exact operative technique varied depending on the status of the lesion. The patients were non-weight bearing for 2 months, after which a second surgery was necessary for removal of the metallic screw(s). The initial healing response was assessed by the firmness of the lesion to palpation at the second look. Subsequent x-ray evidence of healing was correlated with the clinical outcome. Ninety-four percent of the knees were determined to be initially healed at the time of the second look. Four of these apparently solid repairs subsequently loosened and required repeat surgery. Eighty-eight percent of the patients assessed their results as excellent or good after 2 years minimum follow-up. Arthroscopic compression screw fixation is an effective method of repair for mild to moderately severe cases of osteochondritis dissecans.

Adult↗
PubMed1990

Apparent lack of H-Y-specific suppressor cells in female mice given male spleen cells intravenously.

Mice given a pretransplant i.v. infusion of spleen cells from donors incompatible with the recipients with respect to individual minor H antigens exhibit a delayed rejection of skin grafts from these incompatible donors. Attempts were made to detect suppressor T cells, possibly induced by the i.v. infusion of donor cells, among spleen cells from female mice made hyporesponsive to H-Y antigen by an i.v. infusion of male spleen cells. When transferred to nonimmune immunocompetent mice, lymphoid cells from hyporesponsive females delayed the rejection of male skin grafts only slightly. Similar results were obtained when putative suppressor cells were transferred to immunodeficient hosts having had their potential to reject male skin grafts restored with either nonimmune or specifically immune female lymphoid cells. The observed suppression of graft rejection could be accounted for, to a significant extent, by male spleen cells carried over with the transferred female cells to the assay recipients. Though an active host-derived suppressor mechanisms was not found, transferred spleen and lymph-node cells obtained from females given a prior i.v. infusion of male spleen cells were poor at restoring the capacity to reject male skin grafts to immunodeficient female recipients, whereas equal numbers of lymphoid cells from untreated females were much better. Thus, i.v. infusion of male spleen cells appeared to deplete the peripheral lymphoid tissue of the recipients of responsivity to H-Y antigen.

Animals↗
PubMed1990

Transcription-dependent competition for a host factor: the function and optimal sequence of the phage lambda boxA transcription antitermination signal.

Ordered development of lambdoid phages relies on systems of transcription termination and antitermination. The phage-encoded N early regulatory proteins, acting with the Nus proteins of Escherichia coli, modify RNA polymerase to a form that overrides many transcription termination signals. These modifications require cis-acting sites, nut, located downstream of the early phage promoters. The nut sites in phages lambda, 21, and P22, which share similarities but are not identical, contain two signals, boxA and boxB. We demonstrate that although a consensus sequence for the boxA signal (boxAcon), 5'CGCTCTTTA, is found only in P22, changes to consensus in the nutR sites of lambda and 21 create more effective antitermination signals than the wild-type signals. An in vivo competition assay demonstrates that a lambda nut region with boxAcon outcompetes nut regions with wild-type, as well as other variations of the boxA sequence, for the host NusB protein. This suggests that boxA influences NusB activity in N-mediated antitermination. Successful competition by boxAcon requires transcription of the nut site as well as N activation. Nucleotide replacement further demonstrates that bases at both ends of boxA are important for antitermination.

Bacterial Proteins↗
PubMed1990

Dual isotope thallium and indium antimyosin SPECT imaging to identify acute infarct patients at further ischemic risk.

Forty-two patients (28 men and 14 women) with acute myocardial infarction (35 Q, seven non-Q wave) were injected with 2.0 mCi indium 111-labeled antimyosin (AM) monoclonal antibody (111In AM) within 48 hours of the onset of chest pain. Forty-eight hours later (72-96 hours after onset of chest pain), patients were injected with 2.2 mCi thallium 201, and two sets of single-photon emission computed tomography (SPECT) images were obtained simultaneously using dual energy windows set for the 247 keV indium photopeak and the 70 keV thallium peak. Seventeen patients had repeat scans at 4 hours. 111In AM uptake and 201Tl defects were localized to one or more of 24 coronal and sagittal segments. Scans with only 201Tl defects and corresponding 111In AM uptake were classified as matches; scans with unmatched 201Tl defects in addition to matching regions corresponding to electrocardiographic infarct location were classified as mismatches; and scans with 201Tl and 111In AM uptake in the same segments were classified as overlap. Scan patterns were correlated with clinical evidence for residual ischemia occurring within 6 weeks of infarct and including infarct extension, recurrent angina, and positive predischarge low-level or 6-week symptom-limited stress tests and with coronary anatomy. Fourteen patients had only matching patterns (group 1), 23 had mismatches (group 2), and five had 201Tl-111In overlap as the predominant pattern. None of the patients in group 1 had previous myocardial infarction; in each, the matched area corresponded to the Q wave location on electrocardiogram, and none had further in-hospital ischemic events or positive stress tests.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1990

Tumour-induced immunity to H-Y-disparate skin grafts without concomitant priming of CTL.

A tumour, ET-5, arising as a subcutaneous mass in a C57BL/6 male mouse after treatment with a mutagen, has been found to elicit immunity to H-Y antigen in B6 female mice that have rejected the tumour. Anti-H-Y immunity is demonstrable in vivo by accelerated rejection of male skin grafts, and by the ability of spleen cells from ET-5-primed female mice to transfer immunity against H-Y antigen to immunodeficient hosts given indicator male skin grafts. However, spleen cells from ET-5-immune female mice fail to generate CTL specific for H-Y antigen when co-cultured with male stimulator cells in vitro. This finding implies that the generation of H-Y-specific immunity in vivo can occur in the absence of priming of CTL, and thus calls into question the necessity for CTL participation in H-Y-disparate tumour graft rejection.

Animals↗
PubMed1989

Measurement of acute Q-wave myocardial infarct size with single photon emission computed tomography imaging of indium-111 antimyosin.

Myocardial infarct size was measured by single photon emission computed tomography (SPECT) following injection of indium-111 antimyosin in 27 patients (18 male and 9 female; mean age 57.4 +/- 10.5 years, range 37 to 75) who had acute transmural myocardial infarction (MI). These 27 patients represent 27 of 35 (77%) consecutive patients with acute Q-wave infarctions who were injected with indium-111 antimyosin. In the remaining 8 patients either tracer uptake was too faint or the scans were technically inadequate to permit infarct sizing from SPECT reconstructions. In the 27 patients studied, infarct location by electrocardiogram was anterior in 15 and inferoposterior in 12. Nine patients had a history of prior infarction. Each patient received 2 mCi of indium-111 antimyosin followed by SPECT imaging 48 hours later. Infarct mass was determined from coronal slices using a threshold value obtained from a human torso/cardiac phantom. Infarct size ranged from 11 to 87 g mean 48.5 +/- 24). Anterior infarcts were significantly (p less than 0.01) larger (60 +/- 20 g) than inferoposterior infarcts (34 +/- 21 g). For patients without prior MI, there were significant inverse correlations between infarct size and ejection fraction (r = 0.71, p less than 0.01) and wall motion score (r = 0.58, p less than 0.01) obtained from predischarge gated blood pool scans. Peak creatine kinase-MB correlated significantly with infarct size for patients without either reperfusion or right ventricular infarction (r = 0.66). Seven patients without prior infarcts had additional simultaneous indium-111/thallium-201 SPECT studies using dual energy windows.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Antimyosin imaging in acute transmural myocardial infarctions: results of a multicenter clinical trial.

Murine monoclonal antimyosin antibody has been shown experimentally to bind selectively to irreversibly damaged myocytes. To evaluate the safety and efficacy of monoclonal antimyosin for identifying acute transmural infarction, 50 patients with acute Q wave myocardial infarction were entered into a phase I/II multicenter trial involving three clinical sites. Indium-111 antimyosin was prepared from an instant kit formulation containing 0.5 mg of diethylene triamine pentaacetic acid (DTPA)-coupled Fab fragment (R11D10) and 1.2 to 2.4 mCi of indium-111. Average labeling efficiency was 92%. Antimyosin was injected 27 +/- 16 h after the onset of chest pain. Planar or tomographic imaging was performed 27 +/- 9 h after injection in all patients, and repeat imaging was done 24 h later in 39 patients. Of the 50 patients entered, 46 showed myocardial uptake of antimyosin (sensitivity 92%). Thirty-one of 39 planar scans performed at 24 h were diagnostic; 8 showed persistent blood pool activity that cleared by 48 h. Focal myocardial uptake of antimyosin corresponded to electrocardiographic infarct localization. No patient had an adverse reaction to antimyosin. In addition, 125 serum samples, including 21 collected greater than 42 days after injection, were tested for human antimouse antibodies, and all samples were assessed as having undetectable titers. Intensity of antimyosin uptake was correlated with infarct location and the presence or absence of collateral vessels. There was a significant correlation between faint uptake and inferoposterior infarct location. In 21 patients who had coronary angiography close to the time of antimyosin injection, there was a significant correlation between faint tracer uptake and closed infarct-related vessel with absent collateral flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

The role of antimyosin antibodies in acute myocardial infarction.

Antimyosin is an Fab fragment of a monoclonal antibody that binds with human myosin exposed in myocytes irreversibly damaged by an ischemic event. Labeled with 111In, the antibody is taken up into acutely necrotic tissue and can be imaged by planar or single photon emission computed tomography (SPECT) techniques. A large, multicenter clinical trial has demonstrated a high degree of both sensitivity for detecting infarction and specificity for excluding a recent ischemic event in patients admitted with chest pain syndrome. No allergic reactions to antibody injection have occurred, nor have there been documented significant increases in human antimouse antibody titers postinjection. Due to relatively slow blood clearance, the optimal imaging time is 24 to 48 hours post-injection. Between 13% and 21% of 24-hour scans are nondiagnostic due to persistent blood pool activity. In two thirds of these patients, 48-hour scans confirm negative tracer uptake. Moderate to intense cardiac uptake occurs in greater than 80% of scans. Faint tracer uptake, which occurs in a small minority of patients, is associated with inferoposterior infarct location and an occluded infarct vessel. Potential clinical uses include both diagnostic and prognostic areas. A negative scan in a patient with chest pain syndrome and no ECG changes rules out a recent significant ischemic event. The extent of antimyosin uptake (infarct size), measured semiquantitatively from planar scans or quantitatively from SPECT reconstructions, has been shown to correlate with future cardiac events. Relative patterns of distribution of indium-antimyosin and 201TI on simultaneous dual isotope SPECT reconstructions may identify patients with residual myocardium at further ischemic risk.

Antibodies, Monoclonal↗
PubMed1989

Identification of Clostridium difficile in stool specimens by culture-enhanced gas-liquid chromatography.

We have developed a sensitive and specific method for the identification of Clostridium difficile in stool specimens based on the detection of metabolic breakdown products of the organism by gas-liquid chromatography after incubation of stool samples in a selective broth medium containing cefoxitin. Use of this approach to test samples from two different populations of patients at separate medical centers showed this method to be superior to plate cultures or cytotoxin testing alone for both populations. The combined results from the two patient populations showed that 225 of 226 confirmed isolates were identified correctly, resulting in a sensitivity of 99.6% and a specificity of 99.0%. This method eliminates the delay caused by subculturing for tests requiring a pure isolate. The culture phase amplifies even low numbers of C. difficile in fecal samples (due to low in vivo concentrations or delayed transport) and thus increases sensitivity. Other advantages include the ability to detect C. difficile in the mixed flora of the stool and the ability of most clinical laboratories to use this procedure. Given the complexities of the detection of C. difficile toxins and the increasing importance of this organism as a nosocomial agent, culture-based methods remain the preferred approach to screening and routine workup for cases of diarrhea.

Adult↗