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Biomedical subjects

L L Johnson

Publications and source records attributed to L L Johnson.

At least 127 records · Page 7Linked to original sources

Prolonged minor allograft survival in intravenously primed mice. Effect of recipient's age and of prior immunity to minor H antigens on the priming cells.

The effect of a pretransplant i.v. infusion of donor-strain spleen cells into recipient mice that were already immune to minor H antigens on the infused cells was studied. The central finding is that a preexisting state of immunity against target minor H antigens on a skin graft is sufficient to overcome the survival-prolonging effect of a pretransplant i.v. infusion of donor-strain spleen cells. Moreover, immunity directed against an irrelevant antigen on the infused cells, rather than against a target antigen on the indicator skin graft, is sufficient to cause the beneficial effect of the infusion to be greatly reduced. A further significant finding is that the ability of a pretransplant infusion of donor-strain spleen cells to prolong the survival of a minor allograft of skin declines as the recipient matures from a 6-9-week-old juvenile to a 12-16-week-old adult.

Aging↗

Myocardial perfusion imaging with technetium-99m SQ30217: comparison with thallium-201 and coronary anatomy.

Myocardial perfusion in ten normal volunteers and 20 patients with coronary artery disease documented by recent coronary arteriography was studied with 99mTc-labeled SQ30217 and 201TI. Plantar 201TI imaging followed standard treadmill exercise and planar SQ30217 imaging followed upright bicycle exercise, performed to angina, or the same double product achieved on the treadmill test. Upright anterior, 30 degrees left anterior oblique, and 60 degrees left anterior oblique images were obtained for 3, 6, and 9 min, respectively, starting 2 min after injection of 15 mCi of 99mTc SQ30217. A second 15-mCi dose was injected at rest approximately 2 hr later, and the same imaging protocol was followed. No adverse reactions or laboratory abnormalities attributable to SQ30217 were observed. All scans on the normal volunteers were interpreted as normal. Qualitative readings of both tests were equally sensitive for detecting patients with coronary disease (SQ30217 - 16/20, TI - 17/20, p = NS) and identifying abnormal vessels (SQ30217 - 19/45, TI - 21/45, p = NS). Both agents were falsely positive in 1/15 vessels. Ten vascular regions showed persistent abnormalities on resting SQ30217 scans; eight of these were distal to stenoses of at least 90% and three were also abnormal on thallium redistribution images. Hepatic uptake of SQ30217 obscured inferoapical segments in some views in 14/20 patients but did not interfere with abnormal vessel identification.

Adult↗

The activator protein for glucosylceramide beta-glucosidase from guinea pig liver. Improved isolation method and complete amino acid sequence.

beta-Glucosidase activator (SAP-2) is a family of heat-stable, acidic glycoproteins which stimulate enzymatic hydrolysis of glucosylceramide. In this study, we improved the purification method and found that SAP-2 is highly heterogeneous. A hot water extract of frozen guinea pig liver was fractionated by ammonium sulfate sedimentation, then chromatographed with DEAE-Sephacel, Sephadex G-75, and concanavalin A-Sepharose. A fraction binding to concanavalin A-Sepharose was purified further with a C4 high performance liquid chromatography reverse phase column. This yielded several peaks, the main one of which was studied. The specific activity of the purified SAP-2 was 35 units/micrograms (1 unit produces 50% stimulation of a basal glucosidase preparation). N-terminal amino acid sequencing showed that this preparation is a mixture of polypeptides differing in the presence or absence of one or two of the end amino acids. The complete amino acid sequence of the 81 residues in SAP-2 has been determined. Comparison of the sequence of guinea pig SAP-2 with the sequence of human sphingomyelinase activator revealed 58% homology and quite similar hydropathy profiles. Both proteins possess a highly hydrophilic region around Asn-22, which is glycosylated, and 6 cysteine residues, in oxidized form, located in the same positions. Comparison with the published nucleotide sequence for the precursor form of the human activator protein for sulfatide sulfatase (SAP-1) suggested that this activator also has a possibly glycosylated Asn and 6 Cys residues at similar positions, although the remainder of the molecule is somewhat different. Examination of another region of the precursor's nucleotide sequence, assuming a few changes in the identifications, revealed the presence of the sphingomyelinase activator. It appears that two or more activators are derived from a single precursor protein. Marked homologies were seen also with a lung surfactant protein and a sulfated glycoprotein from Sertoli cells.

Amino Acid Sequence↗

Antigraft responses to the H-28c antigen by B6 and B6D2F1 mice.

The survival of minor H antigen-bearing skin grafts from donors congenic with C57BL/6 (B6) was compared in B6, B6D2, and AB6 hybrid recipients. In a case singled out for further study, B6 mice were found to reject HW110 skin (H-28c antigen) rapidly, whereas B6D2 mice rejected HW110 skin much more slowly and variably. Both major histocompatibility complex (MHC)-linked and non-MHC genes appeared to affect the survival of HW110 strain skin grafts on B6 and B6D2 recipients. Results of several experiments appear to rule out the sharing of H-28c epitopes between donors and recipients as an explanation for the relatively poor response of B6D2 mice to HW110 skin grafts. Experiments involving bone marrow chimeras produced by the reciprocal exchange of bone marrow between irradiated B6 and B6D2 mice suggest that bone marrow-derived donor cells and non-bone-marrow-derived host cells each contribute to the immune response phenotype with respect to the H-28c antigen. An attempt was made to determine whether B6D2 mice that failed to reject HW110 strain skin grafts possessed suppressor cells specific for the H-28c antigen. Spleen cells from poorly responsive B6D2 mice failed to suppress the rejection of HW110 skin grafts when assayed in immunodeficient mice that were provided with cells from immune B6D2 donors that were highly responsive to HW110 skin grafts.

Animals↗

Risk of myocardial ischaemia during anaesthesia in treated and untreated hypertensive patients.

Hypertensive patients were monitored for myocardial ischaemia during anaesthesia and surgery with the V5 lead of a standard electrocardiograph. Myocardial ischaemia was detected in 11 of 39 untreated hypertensive patients and in four of seven receiving therapy with a diuretic, but in none of 44 receiving atenolol. Fourteen of the atenolol-treated patients were receiving the drug on a long-term basis and the remaining 30 were treated acutely only on the morning of surgery. When myocardial ischaemia was observed, it was always associated with noxious stimulation and tachycardia, but a conspicuous increase in arterial pressure was not usually present. We conclude that myocardial ischaemia is prevalent during anaesthesia in untreated hypertensive patients, and that pretreatment with atenolol, but not diuretics, provides prophylaxis.

Anesthesia↗

Hemodynamic effects of labetalol in patients with combined hypertension and left ventricular failure.

To investigate the safety of labetalol in the treatment of hypertension in patients with heart failure, sixteen hypertensive patients with a history of congestive heart failure and an ejection fraction at rest less than 45%, had measurements of ejection fraction and cardiac output by first pass radionuclide angiography at baseline, at the end of 2 weeks maintenance with labetalol (titrated to the effective antihypertensive dose of 200-1600 mg daily), and in the post-treatment placebo period. On labetalol, heart rate and blood pressure were significantly lower than placebo at rest and the ejection fraction was higher (30 vs 25%) (p less than 0.05). At maximal exercise on labetalol the heart rate and blood pressure were lower than at placebo maximal exercise (p less than 0.05) and the ejection fraction was higher (32 vs 27%) (p less than 0.01). Exercise tolerance was not changed by labetalol. No patient was discontinued from the study because of worsening heart failure. Dizziness was reported in 5 of 16 patients usually at one visit. Dyspnea that was reported in 4 of 16 patients improved with minor adjustments in digitalis or diuretic dose. In conclusion, labetalol reduces blood pressure in hypertensive patients with left ventricular dysfunction without reducing cardiac performance.

Angiography↗

Failure of intravenously infused spleen cells bearing a minor histoincompatibility to delay rejection of skin grafts bearing additional antigens.

Intravenous infusions of spleen cells bearing single minor H antigens have been shown to induce an antigen-specific prolongation of survival of subsequently applied skin grafts bearing the infused antigen. In this report it is shown that i.v. infusion of spleen cells bearing only H-Y as an alloantigen fails to prolong the survival of subsequently applied skin grafts bearing H-Y and additional H antigens. In contrast, others have shown that the i.v. infusion of alloantigen-bearing cells can inhibit DTH reactions, CTL generation, or organ allograft rejection directed against additional alloantigens, provided they are present in the challenge inoculum or graft together with the i.v.-infused antigens. Several possible reasons for the discrepancy between the results with skin grafts, and the results of others using different assays of responsiveness to H antigens are examined.

Animals↗

Comparison of two screen-film combinations in contact and magnification mammography: detectability of microcalcifications.

A new dual-screen, dual-emulsion-film combination that allows a decrease in radiation dose of approximately 66% was compared with a widely used single-screen, single-emulsion-film system in contact and magnification mammography. Clustered microcalcifications randomly superimposed on a breast phantom were detected, and the location and number of individual calcifications were determined by four observers. The detectability of calcifications, determined with a receiver operating characteristic (ROC) analysis area, was 0.92 for magnification and 0.82 for contact mammography with the single-emulsion-film system, compared with 0.84 and 0.72, respectively, with the dual-emulsion-film system. More clusters were correctly located and more individual calcifications were counted with magnification than with contact mammography. The dual-emulsion-film system with the magnification technique performs as well as the single-emulsion-film system with the contact technique, while retaining a decrease in required dose of approximately 40%.

Breast Diseases↗

Myocardial ischemia in untreated hypertensive patients: effect of a single small oral dose of a beta-adrenergic blocking agent.

In a non-double-blind, prospective, randomized study, the intra-operative electrocardiograms of 128 mildly hypertensive surgical patients were examined in order to determine the incidence of myocardial ischemia during anesthesia. No patient had been receiving chronic antihypertensive therapy prior to the study, but a single small oral dose of a beta-adrenergic blocking agent (labetalol, atenolol, or oxprenolol) was given to 89 of them along with premedication. Forty-four per cent of the untreated control patients and 61% of the patients pretreated with a beta-adrenergic blocking agent had normal preoperative electrocardiograms and no risk factors for coronary artery disease other than hypertension (this difference between groups was not statistically significant). During tracheal intubation and/or emergence from anesthesia, a brief, self-limited episode of myocardial ischemia was detected in 11 of 39 untreated control patients, and in two of 89 patients pretreated with a beta-adrenergic blocking agent (P less than 0.001). Tachycardia always accompanied the ischemic events, but a conspicuous increase in blood pressure did not. The authors conclude that mild hypertension, when untreated prior to the induction of anesthesia, is associated with a high incidence of myocardial ischemia; and that a single small oral dose of a beta-adrenergic blocking agent, given with pre-medication, can significantly reduce that risk.

Administration, Oral↗

Complete amino acid sequence of human serum cholinesterase.

The complete amino acid sequence of human serum cholinesterase (choline esterase II (unspecific), EC 3.1.1.8) was determined by Edman degradation of purified peptides. The protein contains 574 amino acids per subunit and nine carbohydrate chains attached to 9 asparagines. The four subunits of cholinesterase appear to be identical. The active site serine is the 198th residue from the amino terminus. The sequence of human serum cholinesterase is 53.8% identical with the sequence of acetylcholinesterase from Torpedo californica and 28% identical with the carboxyl-terminal portion of bovine thyroglobulin.

Amino Acid Sequence↗

Imaging of cardiac allograft rejection in dogs using indium-111 monoclonal antimyosin Fab.

The acute rejection of cardiac allografts is currently diagnosed by the presence of myocyte necrosis on endomyocardial biopsy. We evaluated the efficacy of noninvasive scintigraphic imaging with indium-111-labeled anticardiac myosin Fab fragments (indium-111 antimyosin) to detect and quantify cardiac allograft rejection. Six dogs that had intrathoracic heterotopic cardiac allograft transplantation were injected with indium-111 antimyosin and planar and single photon emission computed tomographic (SPECT) images were obtained in various stages of acute and subacute rejection. Four dogs had an allograft older than 8 months and had been on long-term immunosuppressive therapy; two dogs had an allograft less than 2 weeks old and were not on immunosuppressive therapy. Count ratios comparing heterotopic with native hearts were calculated from both SPECT images and in vitro scans of excised and sectioned hearts and were compared with the degree of rejection scored by an independent histopathologic review. Indium-111 antimyosin uptake was not visible in planar or SPECT images of native hearts. Faint diffuse uptake was apparent in cardiac allografts during long-term immunosuppression and intense radioactivity was present in hearts with electrocardiographic evidence of rejection. The heterotopic to native heart count ratios in SPECT images correlated significantly with the count ratios in the excised hearts (r = 0.93) and with the histopathologic rejection score (r = 0.97). The distribution of indium-111 antimyosin activity in right and left ventricles corresponded to areas of histopathologic abnormalities. Immunoperoxidase studies showed deposition of indium-111 antimyosin only in areas of myocyte necrosis. The results demonstrate that indium-111 antimyosin imaging can noninvasively detect the presence, location and severity of canine cardiac allograft rejection.

Animals↗

Prolonged minor allograft survival in intravenously primed mice--a test of the veto hypothesis.

Experiments were performed to test the hypothesis that veto cells are responsible for the prolonged survival of minor allografts of skin that is observed in recipients primed intravenously with spleen cells from mice syngeneic with the skin donors. This prolonged survival was observed for each of several minor histocompatibility (H) antigens and is antigen-specific. Gamma radiation (3300 rads) abolished the ability of male spleen cells infused i.v. to delay the rejection of male skin grafts (H-Y antigen) on female recipients. However, depletion of Thy-1+ cells from the i.v. infusion failed to abolish the ability to prolong male skin graft survival. Furthermore, the prolonged survival accorded to B6 (H-2b) male skin grafts on CB6F1 (H-2b/H-2d) female recipients given i.v. infusions of B6 male spleen cells extended to BALB/c (H-2d) male skin grafts as well, indicating a lack of MHC restriction. Thus, prolongation of minor allograft survival by i.v. infusion of minor H antigen-bearing spleen cells appears not to depend on veto T cells that others have found to be responsible for the suppression of CTL generation (2, 3, 5).

Animals↗

Measurement of infarct size and percentage myocardium infarcted in a dog preparation with single photon-emission computed tomography, thallium-201, and indium 111-monoclonal antimyosin Fab.

Single photon-emission tomography (SPECT) and indium 111-labeled monoclonal antimyosin Fab fragments were used to measure myocardial infarct size in 12 dogs, six subjected to balloon catheter-induced coronary artery occlusion for 6 hr (late reperfusion) and six subjected to occlusion with reperfusion at 2 hr (early reperfusion). Tomographic imaging was performed 24 hr after the intravenous injection of labeled Fab fragments with the use of a dual-head SPECT camera with medium-energy collimators. Immediately after the first tomographic scan, thallium-201 was injected into nine of 12 dogs and imaging was repeated. Estimated infarct size in grams was calculated from transaxially reconstructed, normalized, and background-corrected indium SPECT images with the use of a threshold technique for edge detection. Estimated noninfarcted myocardium in grams was calculated from obliquely reconstructed thallium SPECT images by a similar method. The animals were killed and infarct size in grams and true infarct size as a percentage of total left ventricular myocardial volume were measured by triphenyl tetrazolium chloride staining. Estimated infarct size from indium SPECT images showed an excellent correlation with true infarct size (r = .95, SEE = 4.1 g). Estimated percentage myocardium infarcted was calculated by dividing estimated infarct size from indium images by the sum of estimated infarct size plus estimated noninfarcted myocardium obtained from thallium images. Correlation between the estimated percentage of myocardium infarcted and true percentage of myocardium infarcted was excellent (r = .93, SEE = 4.4%). We conclude that dual-isotope SPECT with indium 111-monoclonal antimyosin antibodies and thallium-201 can accurately estimate infarct size and percentage myocardium infarcted.

Animals↗

Cardiovascular effects of imipramine and bupropion in depressed patients with congestive heart failure.

There has been a long-standing concern over the cardiovascular effects of tricyclic antidepressants, particularly in patients with preexisiting cardiac disease. Recent studies have demonstrated that imipramine causes no deleterious effect on ejection fraction as determined by radionuclide angiography in patients with impaired left ventricular function (LVF). However, the high rate of severe orthostatic hypotension induced by imipramine makes use of the drug problematic in these patients. Bupropion is a new antidepressant of the aminoketone class which is structurally unrelated to the tricyclics and which is relatively free of cardiac side effects in healthy depressed patients. We compared imipramine and bupropion in 10 depressed patients with impaired LVF in a random, double-blind crossover study. Neither imipramine nor bupropion adversely affected ejection fraction or other indices of LVF. However, as previously reported, severe orthostatic hypotension requiring discontinuation of drug developed in 50% of patients on imipramine. This difficulty did not occur with bupropion. From a cardiac perspective, bupropion may offer a safe alternative to imipramine in depressed patients with congestive heart failure.

Aged↗

The shoulder joint. An arthroscopist's perspective of anatomy and pathology.

Arthroscopy has had a great impact on shoulder surgery by adding another dimension to the surgical anatomy. The present benefits of arthroscopy of the shoulder include the establishment of an accurate diagnosis in the glenohumeral joint, subacromial space, and acromioclavicular joint. Various pathologic entities can be visualized. The efficacy and end results of several arthroscopic surgical procedures are under investigation. Patient selection, the pathologic diagnosis, and end results are important considerations in evaluating newly devised arthroscopic methods of treatment of shoulder syndromes.

Arthroscopy↗

Nortriptyline in depressed patients with left ventricular impairment.

Previous studies of the effect of tricyclic antidepressants on left ventricular function in depressed patients with moderate to severe ventricular impairment have focused primarily on imipramine hydrochloride. In a prior study, we found that although imipramine had no effect on ejection fraction as measured by first-pass radionuclide angiography, the treatment could not be tolerated by 50% of the patients because of intolerable drug-induced orthostatic hypotension. Nortriptyline hydrochloride is an effective antidepressant that, in depressed patients without heart disease, causes significantly less orthostatic hypotension than imipramine. To see if this advantage could be safely extended to patients with congestive failure, we measured the effect of nortriptyline on ejection fraction and blood pressure in 21 depressed patients with left ventricular impairment. Ejection fraction was unchanged by nortriptyline treatment, and orthostatic hypotension developed in only one (5%) of 21 patients. Nortriptyline emerges as a relatively safe treatment for depression in patients with left ventricular impairment.

Aged↗