H-2 class I and Gt (H-2) antigens are identical: evidence from H-2 mutant mice.
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Biomedical subjects
Publications and source records attributed to L L Johnson.
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The ability of radionuclide techniques to localize bypass tracts in patients with Wolff-Parkinson-White syndrome to sites around the atrioventricular (AV) ring using a three view triangulation method was investigated. In 17 patients with Wolff-Parkinson-White syndrome, phase images were generated from gated blood pool scans using the first Fourier harmonic of the time-activity curve of each pixel. In addition, the difference between left and right ventricular mean phase angles was calculated for each patient and for 13 control subjects. Bypass tracts were localized to one or more sites on a 10 site grid schematically superimposed on the AV ring (Duke grid) by electrophysiologic study in all patients and by intraoperative mapping in 7 of the 17 patients. These same 10 anatomic sites were projected onto three scintigraphic views and the site of earliest ventricular phase angle was located in each view. The 10 sites around the AV ring were divided into two anatomic groups: free wall and septal/paraseptal. Phase image locations correlated with electrophysiologic locations within one grid site in 11 of 11 patients with free wall tracts and were confirmed at surgery in 5 of the 11. In five of six patients with septal/paraseptal tracts, electrophysiologic study could not localize the bypass tract to one site, whereas phase images localized two of the five as free wall adjacent to the septum, one as paraseptal and two as true posteroseptal. One posteroseptal site was confirmed at surgery. In one patient, in whom phase image analysis and electrophysiologic study showed different sites, existence of both tracts was confirmed at surgery.(ABSTRACT TRUNCATED AT 250 WORDS)
Arthroscopic abrasion arthroplasty is a modification of open Magnusson "housecleaning" arthroplasty. The arthroscopic approach decreases incision size enhancing postoperative rehabilitation. Arthroscopic techniques enhance the accuracy of diagnosis and provide accuracy of limiting debridement only to diseased tissue in various other dimensions of arthroplasty. The abrasion of a sclerotic lesion superficially removes dead bone, exposes vascularity providing a tissue bed for blood clot attachment. Postoperative joint protection provides an environment for clot organization and fibrous tissue formation. Subsequent fibrocartilage formation has maintained integrity for up to 6 years, the extent of experience. The clinical indication is pain. The patient benefit, therefore, is also subjective. Objective evidence of healing response is demonstrated by second-look arthroscopy, biopsy, and comparison x-ray films. If nothing else, these clinical and pathological observations have challenged "established concepts" and opened new vistas for investigation.
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Evidence is presented of the ability of H-2 class I antigens to function as teratocarcinoma transplantation (Gt) antigens. Coisogenic immunization against H-2 class I antigens expressed on transfected L cells is shown to induce resistance to embryonic carcinoma (EC) cell allografts. The Kb, Db, Dd, and, in appropriate recipients, Ld antigens can function as Gt antigens. The protocol presented may be useful for the molecular identification of other genes encoding histocompatibility antigens.
The effect of imipramine or nortriptyline on left ventricular function and orthostatic blood pressure was evaluated in 20 nondepressed cardiac patients treated for ventricular premature depolarizations (VPDs). Drug was administered by mouth and dose ranging used, 1 mg/kg/day (imipramine) or 0.5 mg/kg/day (nortriptyline), was increased after four doses (imipramine) or six doses (nortriptyline) until greater than 80% suppression of VPDs or adverse effects occurred or until a maximum dose of 5 mg/kg/day (imipramine) or 3.5 mg/kg/day (nortriptyline) was given. Fourteen (70%) had greater than 80% VPD suppression, five had less than 80% improvement (range 25% to 77%), and one had a VPD frequency increase of 6%. Mean daily imipramine dose was 210 +/- 103 mg and mean nortriptyline dose was 100 +/- 29 mg. Neither drug significantly changed mean ejection fraction or peak systolic pressure end-systolic volume ratio by radionuclide angiogram. Both reduced standing systolic blood pressure: mean change after imipramine was 26 mm Hg (NS), and after nortriptyline, 14 mm Hg (p less than 0.05). Drug was discontinued in two patients because of symptomatic orthostatic blood pressure change greater than 30 mm Hg. There was not a significant relationship between dose, drug concentration, or functional class and orthostatic change in systolic blood pressure but there was for age (p less than 0.05). These observations suggest that even cardiac patients with impaired systolic function may take imipramine or nortriptyline for VPDs; however, frequent blood pressure measurement is advised, particularly in older patients.
Timed pregnant (8 days) Sprague-Dawley rats were fed ground stock diet (CON) or ground stock diet with 4% cholestyramine (CTR) until day 20 of gestation. Animals in both groups gained weight equally well during the study period (CON (n = 7), 308 +/- 7 g; CTR (n = 6), 315 +/- 7 g, mean +/- SEM). At the end of the study period, plasma cholesterol in the CTR group was significantly greater than that in the control group (CON n = 7, 91 +/- 4 mg/dl; CTR (n = 6), 108 +/- 5 mg/dl, P less than 0.05). The fecal excretion of both neutral steroids and bile acids, studied for 3 days between days 15 and 18 of gestation, was significantly enhanced by CTR treatment. (Neutral steroids: CON, 3.9 +/- 0.3; CTR, 10.4 +/- 0.3, P less than 0.05. Bile acids: CON, 7.6 +/- 0.4; CTR, 25.8 +/- 1.7, P less than 0.05, mg/100 g body wt/day). Bile acid pool size, measured at day 20 of gestation, however, was not significantly different. Consistent with these results was the finding that hepatic cholesterol 7 alpha-hydroxylase activity (the rate-limiting enzyme of bile acid biosynthesis) measured at day 20 of gestation was significantly enhanced by CTR treatment (CON (n = 4), 14.7 +/- 1.7; CTR (n = 4), 34.8 +/- 3.3, pmoles/mg/min, P less than 0.05). The atypical finding of hypercholesterolemia, despite the CTR-induced enhanced turnover of cholesterol, may be due to changes in the homeostatic mechanisms of cholesterol and bile acid metabolism during pregnancy.
Peak regional acceleration images were obtained from gated blood pool scans at rest in 10 normal subjects, 16 patients who underwent cardiac catheterization for unstable angina or nontransmural infarction and were found to have normal ejection fraction and wall motion and 10 patients with prior infarction and regional dyssynergy. The second derivative of the time-activity curve of each pixel was generated and the maximal systolic value of the derivative for each pixel was displayed as a functional image (peak regional acceleration). Anterior and left anterior oblique views were evaluated for abnormalities and the presence and location of defects were correlated with the coronary anatomy. The scans from the 10 normal subjects were used to establish the normal range for regional second derivative values. Both gated blood pool scans and second derivative images showed regional abnormalities in all 10 patients with prior transmural infarction. Regional abnormalities were present in the second derivative images in the distribution of 17 of the 20 coronary arteries with greater than 50% stenosis; there were no regional abnormalities in the distribution of 7 of the 8 arteries with less than 50% stenosis. In addition, regional second derivative image abnormalities were present in 15 of the 16 patients with unstable angina and normal wall motion and global ejection fraction. These 16 patients showed regional abnormalities on second derivative images in the distribution of 19 of the 23 coronary arteries with significant stenosis and no regional abnormalities in the distribution of 21 of the 23 coronary arteries without significant stenosis.(ABSTRACT TRUNCATED AT 250 WORDS)
Male-specific antigen expression by XY teratocarcinomas PCC7 and 7' is demonstrated first by the rejection of tumors by female but not by male mice following challenge with these cell lines. Male-specific antigen expression is confirmed by an indirect method in which females are immunized against H-Y antigen by male skin grafts. A variant of PCC7 lacking male-specific antigen expression is described. Analysis of the karyotype and of the DNA from this variant indicate that the loss of male-specific antigen expression is a result of the loss of the Y chromosome. The ability to recover variants that have lost expression of male-specific antigen opens the possibility of their selection after mutagenesis.
The hemodynamic effects of beta-receptor blocking agents on the ejection fraction of patients with coronary artery disease during exercise have been studied previously using radionuclide techniques. Left ventricular volume measurements and the peak systolic pressure/end-systolic volume (PSP/ESV) index have been shown to be variables of left ventricular function that are less influenced by preload and afterload than is ejection fraction. Left ventricular volumes and PSP/ESV were therefore measured in 18 patients with proven coronary artery disease in the control state and after 2 weeks of daily maintenance therapy with either 240 mg propranolol or 60 mg timolol. Values at rest and during symptom-limited upright exercise were compared using the first pass technique and a multicrystal scintillation camera. Left ventricular volumes were measured by the area-length method. Because there was no difference between the propranolol and timolol groups, the results for both groups were combined. The ejection fraction at rest after beta-receptor blocker treatment was not significantly different from pretreatment measurements because of an increase in both end-diastolic and end-systolic volumes (p less than 0.01). However, the value for peak systolic pressure/end-systolic volume (PSP/ESV) index at rest was lower after treatment. The exercise ejection fraction was greater after treatment (p less than 0.01), owing to an increase in end-diastolic volume and unchanged end-systolic volume. In addition, there was a significant improvement in the directional change in the PSP/ESV ratio between rest and exercise from pretreatment to treatment (-1.1 +/- 2.5 to +0.2 +/- 1.2, p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)
Previous studies of left ventricular performance (LVP) in depressed patients receiving tricyclic antidepressants have been performed on patients without severe heart disease. This study reports the effect of imipramine hydrochloride on LVP, assessed by radionuclide angiography, in a group of depressed patients with notable preexisting left ventricular dysfunction. Ejection fraction was measured at rest by first-pass radionuclide angiography before and after treatment with imipramine. Ejection fraction was unchanged during treatment, but seven of 15 patients experienced orthostatic hypotension of such severity that administration of the drug had to be discontinued. Plasma concentrations of the drug were essentially twice those usually seen. It is important to appreciate that although imipramine does not further impair resting LVP, this does not mean it is without risk. The physician must watch carefully for orthostatic hypotension when using imipramine in depressed patients with impaired LVP.
To test the hypothesis that left ventricular (LV) performance in aortic regurgitation (AR) can be more completely characterized by measurement of LV volumes in addition to ejection fraction (EF), 27 asymptomatic patients (Group 1), and 22 symptomatic patients (Group 2), and 10 control subjects were studied at rest and during upright bicycle exercise using the first-pass technique and a multicrystal scintillation camera. LV end-diastolic volume was measured by the area-length method. In the control group end-diastolic volume increased 14%, end-systolic volume decreased 22%, and EF increased 22% with exercise. In contrast, in Group 1 patients with AR, end-diastolic volume was elevated at rest and during exercise. The 18% decrease in end-diastolic volume during exercise was significantly different from the control response (p less than 0.01). End-systolic volume was also elevated at rest and during exercise, but the 30% decrease during exercise was a response not significantly different from the control. Although mean EF increased 15% in these patients, EF at peak exercise was significantly lower than that in the controls. In Group 2 patients with AR, resting EF was reduced, the EF response to exercise was abnormal, and end-diastolic and end-systolic volume responses to exercise were significantly different from those in Group 1: end-diastolic volume did not change and end-systolic volume increased. In contrast to the fairly uniform volume responses among all Group 1 patients, there were 2 subgroups based on volume changes within Group 2: 7 of 22 had a decrease in end-diastolic volume and end-systolic volume during exercise and 8 of 22 showed an increase in end-diastolic and end-systolic volume during exercise. In conclusion, LV volumes at rest and exercise give more information about LV functional reserve in symptomatic patients with AR than do EF responses alone, and may be useful in separating symptomatic patients who show a normal end-systolic volume response to exercise from those in whom worsening failure develops during exercise.
Evidence is presented for the existence of teratocarcinoma transplantation antigens (Gt) encoded within the H-2 complex and present also on adult tissues. It has not been possible to separate these Gt loci from H-2 by recombination, and Gt factors map to each end of the H-2 complex. Previous reports indicating separation of all Gt loci from H-2 are reinterpreted. One class of such apparent recombinants has been shown to result from the outgrowth of tumor variants in mice of resistant genotype.
The hypothesis that exercise-induced myocardial ischemia is associated with abnormal platelet activation and fibrin formation or dissolution was tested in patients with coronary artery disease undergoing upright bicycle stress testing. In vivo platelet activation was assessed by radioimmunoassay of platelet factor 4, beta-thrombo-globulin and thromboxane B2. In vivo fibrin formation was assessed by radioimmunoassay of fibrinopeptide A, and fibrinolysis was assessed by radioimmunoassay of thrombin-increasable fibrinopeptide B which reflects plasmin cleavage of fibrin I. Peripheral venous concentrations of these substances were measured in 10 normal subjects and 13 patients with coronary artery disease at rest and during symptom-limited peak exercise. Platelet factor 4, beta-thromboglobulin and thromboxane B2 concentrations were correlated with rest and exercise catecholamine concentrations to determine if exercise-induced elevation of norepinephrine and epinephrine enhances platelet activation. Left ventricular end-diastolic and end-systolic volumes, ejection fraction and segmental wall motion were measured at rest and during peak exercise by first pass radionuclide angiography. All patients with coronary artery disease had documented exercise-induced myocardial ischemia manifested by angina pectoris, ischemic electrocardiographic changes, left ventricular segmental dyssynergy and a reduction in ejection fraction. Rest and peak exercise plasma concentrations were not significantly different for platelet factor 4, beta-thromboglobulin, thromboxane B2, fibrinopeptide A and thrombin-increasable fibrinopeptide B. Peripheral venous concentrations of norepinephrine and epinephrine increased significantly (p less than 0.001) in both groups of patients. The elevated catecholamine levels did not lead to detectable platelet activation. This study demonstrates that enhanced platelet activation, thromboxane release and fibrin formation or dissolution are not detectable in peripheral venous blood of patients with coronary disease during exercise-induced myocardial ischemia.
A skin grafting protocol is described for finding H-Y antigenic variants. The method is applicable regardless of the location of the structural gene(s) for this antigen (X, Y, or autosomal). Use of this protocol revealed no evidence for H-Y antigenic variation between C57BL/6J and strains 129/J, A.BY/SnJ, C3H.SW/SnJ, and LP/J.
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