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Biomedical subjects

J J Collins

Publications and source records attributed to J J Collins.

At least 253 records · Page 14Linked to original sources

Immunotherapy of murine leukemia. VII. Prevention of Friend leukemia virus-induced immunosuppression by passive serum therapy.

Previous studies have suggested that the passive therapy of Friend leukemia virus (FLV)-induced disease with chimpanzee anti-FLV serum operates by reducing the level of infectious virus in the treated animal below the immunosuppressive threshold, thereby allowing the host to mount anti-viral immune responses which are responsible for long-term protection. The present study was undertaken to examine directly the effect of passive serum therapy on the marked immunosuppression induced by FLV in progressively infected mice, as well as to determine whether virus-specific host cellular immune effector functions are augmented in serum-protected animals. Using a variety of assays of host immunocompetence, including natural killing (NK), antibody-dependent cellular cytotoxicity (ADCC) in vivo and in vitro induction of allogeneic killers, and mitogen blastogenesis, a marked compartmentalization of FLV immunodepression was observed in progressively infected DBA/2 mice, possibly reflecting the distribution of FLV target cells in various host lymphoid populations. Thus, spleen-cell functions were suppressed most rapidly and to the greatest degree, followed by peritoneal cells and peripheral blood lymphocytes, while lymph node cells and thymocytes maintained normal levels of activity. In contrast, serum-protected mice demonstrated no sign of FLV-induced immunosuppression regardless of the host effector-cell population or immune function examined. However, we were not able to identify host anti-viral cellular immune functions which are significantly enhanced in serum-protected animals; thus the specific role of the host immune system in the passive serum therapy of FLV-induced disease remains undefined at the present time.

Animals↗

Inotropic contractile reserve: a useful predictor of increased 5 year survival and improved postoperative left ventricular function in patients with coronary artery disease and reduced ejection fraction.

The increase in left ventricular ejection fraction produced by postextrasystolic potentiation or epinephrine infusion has been used to demonstrate inotropic contractile reserve in patients with coronary artery disease and a depressed ejection fraction (less than 0.50). Prior studies have shown that a change in ejection fraction of 0.10 or more after postextrasystolic potentiation or epinephrine infusion is helpful in discriminating those patients with a better short-term (1 year) prognosis whether treated medically or surgically. This study related inotropic contractile reserve to 5 year prognosis in 54 patients receiving postextrasystolic potentiation or epinephrine infusion between 1971 and 1974. Current left ventricular function in surviving patients was assessed with radionuclide ventriculograms whenever possible. Five year survival was significantly better in patients with an initial change in ejection fraction greater than 0.10 in both the surgically treated group (16 of 20 versus 5 of 15, p less than 0.01) and the medically treated group (6 of 8 versus 1 of 11, p less than 0.01). Furthermore, among the surviving patients in the surgical group, current ejection fraction in the radionuclide ventriculogram was significantly greater in patients who demonstrated inotropic contractile reserve in their 1971 to 1974 contrast left ventriculogram. These findings support the concept that coronary revascularization enhances function of ischemic but viable myocardium.

Angina Pectoris↗

Immunotherapy of murine leukemia VI. Development of immunologic memory in mice protected against Friend leukemia virus-induced disease by passive serum therapy.

The resistance of DBA/2 mice to infection with a leukemogenic dose of Friend leukemia virus (FLV) as a result of the passive administration of chimpanzee anti-FLV serum is maintained for at least six months after infection and is accompanied by the continued synthesis of mouse anti-viral antibodies analogous to that previously found to be associated with short-term protection (approx. 30 days). Furthermore, the induction of immunologic memory in serum-protected mice is demonstrated by their long-term resistance to rechallenge with FLV of FLV-infected leukemic spleen cells, although cells of an established transplantable syngeneic FLV-erythroleukemia (FLC-745) are not rejected. In the course of these studies, a serum prophylaxis effect was defined in DBA/2 mice treated with the chimpanzee anti-FLV serum before, rather than after FLV infection. The prophylaxis effect is highly dependent on the time period between the last serum inoculation and virus challenge. The results indicate that the long-term resistance of therapeutically protected mice to subsequent virus or leukemic cell challenge is not due to the short-term prophylactic effect of serum treatment alone.

Animals↗

Determinants of operative survival following combined mitral valve replacement and coronary revascularization.

To determine the operative survival rate following combined mitral valve replacement (MVR) and coronary artery bypass graft (CABG) operation, we evaluated 100 patients, who were seen consecutively at the Peter Bent Brigham and Brigham and Women's Hospital from 1972 to 1982. There were 63 men and 37 women; the mean age was 62 years. Thirty-six patients were in New York Heart Association (NYHA) Functional Class III, and 64 were in functional Class IV. Mitral regurgitation was predominant in 76 patients; mitral stenosis, in 24. Emergency operations were performed in 15 patients, and elective or semielective operations were performed in 85. There were 18 operative deaths (18%): 9 in patients having elective operations (10.5%) and 9 in those having emergency operations (60%; p less than 0.01). Significant preoperative factors related to operative death were NYHA functional class, increased pulmonary vascular resistance, lower cardiac index, and lower ejection fraction in the nonsurvivors. The rate of survival did not differ according to sex, age, or degree of coronary artery disease. In addition, myocardial protection with potassium cardioplegia and complete coronary revascularization significantly reduced operative mortality in the elective group of patients but did not alter the mortality in the emergency group.

Adult↗

The contribution of medical measures to the decline of mortality from respiratory tuberculosis: an age-period-cohort model.

The decline of mortality in the more developed nations has been related to two major influences, economic development and the introduction of medical measures. The contribution of medical measures has been a source of continuing controversy. Most previous studies employ either a birth cohort or calendar year arrangement of mortality data to address this controversy. The present study applies an age-period-cohort model to mortality from respiratory tuberculosis in England and Wales, Italy, and New Zealand in an attempt to separate economic influences from that of medical measures. The results of the analysis indicate that while the overall contribution of medical measures is small when examined by calendar year, specific birth cohorts both in Italy and in England and Wales benefited substantially from these measures. The environmental conditions in New Zealand, however, were such that the introduction of medical measures barely affected declining mortality levels from respiratory tuberculosis.

Adolescent↗

The stability and structure of cholesterol-rich codispersions of cholesterol and phosphatidylcholine.

In order to investigate the structure and stability of cholesterol-enriched dispersions of phosphatidylcholine (PC), cholesterol/dipalmitoyl phosphatidylcholine (DPPC) mixtures with molar ratios of 4 +/- 0.5/1 to 1/1 were dispersed in water by sonication. These dispersions comprise liposomes and unilamellar vesicles with diameters in the range 200-1800 A. The bilayers which have a repeat distance of 66 A in these particles at 20 degrees C can contain up to 4 mol cholesterol/mol PC when DPPC is used and about half this ratio with egg PC. these dispersions are metastable in that storage at either 4 or 20 degrees C leads to aggregation and precipitation of vesicles; in addition, there is a decrease in the cholesterol/PC molar ratio in the particles and formation of cholesterol monohydrate crystals. Cholesterol is released slowly and PC dispersions containing more than equimolar amounts of cholesterol can be stable for several months. The amount of free cholesterol was determined by differential scanning calorimetry from the heat associated with the transition at 157 degrees C from smectic liquid crystal to liquid cholesterol. Under conditions of gentle mixing, the maximum solubility of cholesterol in DPPC bilayers is 1.0 +/- 0.1 mol/mol PC when the mixture initially contains less than about 3 mol cholesterol/mol DPPC. This is consistent with published equilibrium phase diagrams which show that equimolar PC/cholesterol bilayers are stable in water.

Calorimetry, Differential Scanning↗

The in-hospital risk of rereplacement of dysfunctional mitral and aortic valves.

From January 1, 1972, to January 1, 1981, 1282 consecutive valve replacements were performed at the Peter Bent Brigham Hospital. Fifty-eight of these (4.5%) were rereplacements: 14 for prosthetic valve subacute bacterial endocarditis (SBE), 29 for primary valve dysfunction (PVD) and 15 for perivalvular leak (PVL). Aortic rereplacement was done in 27 patients (eight for SBE, 10 for PVD and nine for PVL) and mitral rereplacement in 31 patients (six for SBE, 19 for PVD and six for PVL). Twenty-six patients were in New York Heart Association functional class III and 32 were in class IV. Ten class IV patients underwent emergency valve replacement (three for SBE, two for PVD and five for PVL). The overall in-hospital mortality rate for valve rereplacement was 14% (eight of 58 patients). For mitral valve rereplacement it was 13% (four of 31), compared with 6.4% (19 of 295) for initial mitral valve replacement. For aortic valve rereplacement, the mortality rate was 15% (four of 27), compared with 5.2% (23 of 440) for initial aortic valve replacement. The cause of death was low cardiac output in six patients, hemorrhage in one patient and sepsis in one patient. All of the patients who died were in functional class IV (p = 0.018). The in-hospital risk for rereplacement of a dysfunctional aortic or mitral valve is no different from that for primary valve replacement unless the patient deteriorates to class IV and requires an emergent operation.

Aortic Valve↗

Acute spontaneous failure of a porcine aortic valve.

The performance of the porcine bioprosthetic heart valve has been well characterized in terms of thrombogenicity, susceptibility to infection, and hemodynamic characteristics. There has been some concern about the frequency and mechanism of late dysfunction of this valve. To date, cases of valve failure have been progressive and gradual. We saw a case of acute, catastrophic, spontaneous failure of a porcine bioprosthetic heart valve. We suggest that in the differential diagnosis of acute aortic insufficiency acute spontaneous failure of a porcine aortic prosthesis be included.

Acute Disease↗

Five to eight-year follow-up of patients undergoing porcine heart-valve replacement.

To evaluate the clinical course after porcine heart-valve replacement, we followed 128 patients for five to eight years after surgery. Aortic-valve replacement was performed in 47 patients, mitral-valve replacement in 62, and combined aortic-valve and mitral-valve replacement in 19. Four patients died within 30 days of surgery (operative mortality, 3 per cent), and 20 died later (16 per cent); the actuarial probability of survival at eight years for all patients was 80 +/- 4 per cent (mean +/- S.E.M.). Thromboemboli were found in two of 43 patients after aortic-valve replacement, in nine of 62 after mitral-valve replacement, and in four of 18 after combined aortic-valve and mitral-valve replacement. Valve dysfunction resulted from bacterial endocarditis in five patients (4 per cent) and from primary valve dysfunction in another five.

Actuarial Analysis↗

Contractile function in chronic gradually developing subcoronary aortic stenosis.

Whether hypertrophied cardiac muscle functions normally or abnormally is a point of controversy in the literature. Most animal studies showing depressed performance of hypertrophied cardiac muscle have used experimental methods in which hypertrophy was produced by acutely imposing a pressure overload on the left or right ventricle, which may cause myocardial injury. To assess the possibility that chronic, slowly developing hypertrophy is associated with normal myocardial function, we developed an experimental model in which increased afterload is imposed gradually on the left ventricle in the dog. A snug band was placed around the aorta beneath the left coronary artery in puppies without producing a stenosis. As the puppies grew, relative aortic stenosis developed as increased cardiac output flowed across that fixed outflow area. One group (group A) of six puppies was banded early, whereas a second group (group B, five puppies) was banded late and served as controls. Left ventricular weight (g) to body weight (kg) ratio remained normal in group B animals (3.9 +/- 0.14), whereas this ratio was increased to 5.3 +/- 0.24 (P < 0.001) in group A animals indicating development of moderate cardiac hypertrophy. Ejection fraction, dP/dt, Vcf, and stroke work per gram of myocardium were virtually identical in both groups. We conclude that moderate, gradually developing cardiac hypertrophy as produced by this model is associated with normal myocardial contractile performance.

Animals↗

Immunotherapy of murine leukemia. V. Protection against Friend leukemia virus-induced immune complex glomerulonephritis by passive serum therapy.

The development of immune complex glomerulonephritis in DBA/2 mice infected with Friend murine leukemia virus (F-MuLV) was compared with that in mice protected against virus-induced disease by administration of chimpanzee anti-F-MuLV antiserum (CaF-MuLV). Morphologic analysis of glomeruli from viremic (infected) normal chimpanzee serum-treated animals revealed significant renal disease within 2 weeks following virus inoculation, with glomerular immune complex deposits and C-type viral particles seen by electron microscopy. Localization of F-MuLV envelope and core antigens (gp71 and p30, respectively) was also detected by immunofluorescence, as was murine IgG and C3. However, age-matched DBA/2 mice treated with CaF-MuLV antiserum alone or following F-MuLV inoculation showed no evidence of systemic disease and neither localization of F-MuLV antigens nor detectable virus particles. These data indicate that in addition to erythroleukemia, F-MuLV infection results in severe immune complex glomerulonephritis and that passive immunotherapy can protect susceptible mice from both aspects of viral pathogenesis.

Animals↗