John J. Trentin

Genetic susceptibility and resistance to diet-induced atherosclerosis and hyperlipoproteinemia.

To test the hypothesis that genetic susceptibility or resistance to diet-induced atherosclerosis is correlated with serum levels of specific lipids, lipoproteins, or apoproteins, male mice of a genetically susceptible and a genetically resistant strain were fed either a normal or an atherogenic diet. After 20 weeks on a normal diet, neither the resistant nor the susceptible strain mice had atherosclerosis; resistant strain mice had serum cholesterol of 66 ± 11 while the susceptible strain mice had 90 ± 1 mg/dl serum cholesterol, and lipoproteins were dominated by a single a-migrating HDL. After 20 weeks on an atherogenic diet, resistant strain mice had 185 ± 55 mg/dl cholesterol, their lipoproteins remained dominated by a-migrating HDL, and two of eight mice had mild atherosclerotic lesions; susceptible strain mice had 510 ± 94 mg/dl cholesterol, multiple a- and pre-R-migrating lipoprotein species, and all 13 had advanced aortic atherosclerosis. The resistant strain mice had an apolipoprotein E/total lipoprotein protein ratio of 0.42 on the normal diet and 0.53 on the atherogenic diet, while the susceptible strain mice had the significantly lower ratios of 0.07 and 0.31, respectively. These data indicate that genetic resistance to diet-induced aortic atherosclerosis in mice is correlated with capacity to prevent large increases in serum cholesterol, to suppress abnormal a- and pre-R-migrating lipoproteins, and to maintain elevated serum apolipoprotein E/total lipoprotein protein ratios. Our data do not preclude the possibility of additional gene control at the level of arterial end organ response.

Cardiac transplantation in mice. I. Factors influencing the take and survival of heterotopic grafts.

Murine hearts were “free grafted‘’ to the pinna of adult mouse ears in order to evaluate immunological and physiological factors influencing the take, survival, and function of myocardial grafts in inbred mice. Visible pulsations, electrical activity, and histology were used to ascertain the viability of the grafted hearts. Cardiac isografts from fetal donors showed slightly better survival (72 of 95) than did those from newborn donors (27 of 40). Twenty-two fetal cardiac isografts in the CBA strain showed 100% survival. Some isografts and parent to F1 semiisografts have pulsated for longer than 2 years. Approximately one-half of unsexed isografted hearts underwent a slow late rejection (within 20–80 weeks) by female but not by male recipients, suggesting that the Eichwald-Silmser effect is operative for cardiac transplants as well as for skin grafts. Y factor immunity was not demonstrated in CBA mice, and isografts to either sex were equally successful (22 of 22 at 86 weeks). F1 to parent and histoincompatible allogeneic heart grafts were rapidly rejected; H-2-incompatible and H-2-compatible allogeneic grafts were rejected within 2 and 3 weeks, respectively. Electrical changes associated with the rejection of the free grafted hearts were characterized by accelerated rate, decreased voltage, and increased incidence of arrhythmia.

Differential Stimulation of Mouse Lymphoid Cells by Phytohemagglutinin and Pokeweed Mitogen

Summary The in vitro response to phytohemagglutinin (PHA) and pokeweed mitogen (PWM) of lymphoid cells from thymectomized, irradiated, bone marrow reconstituted (TIR) mice was compared to that of intact age controls. TIR spleens, lacking cells of the thymus-dependent compartment, responded only to pokeweed mitogen, whereas spleens from intact donors responded to both PHA and PWM. These results suggest that PHA stimulates thymus-dependent cells; whereas PWM stimulates cells of the non-thymus-dependent compartment.

Cellular immunity and blocking serum activity in chimeric mice

Abstract Mice (9 CBA × T6, 6 T6, and 7 CBA) were irradiated and repopulated with foreign (BALB/c) bone marrow. Lymph node cells from 16 of 18 repopulated mice not showing signs of graft versus host disease (GVH), were cytotoxic to host type fibroblasts but not to BALB/c fibroblasts, and sera from the same mice could block lymphocyte mediated cytotoxicity. No blocking was seen with sera from three mice which had signs of GVH. LNC from the latter three mice were cytotoxic to recipient fibroblasts. It is suggested that the blocking effect detected in vitro may protect against GVH in vivo , but the relative importance of the blocking phenomenon as compared to other mechanisms is not yet settled.

Rejection of the transplanted human heart.

Abstract The human heart is highly vulnerable to rejection. In 16 patients with 17 allografts rejection progressed relentlessly in histocompatibility matches of C and D grades. Only three patients ...

Rejection of the Transplanted Human Heart

Abstract The human heart is highly vulnerable to rejection. In 16 patients with 17 allografts rejection progressed relentlessly in histocompatibility matches of C and D grades. Only three patients ...

“Xenogeneic Resistance” to Rat Bone Marrow Transplantation I. The Basic Phenomenon

Summary A phenomenon termed “xenogeneic resistance” to hemopoietic repopulation by rat bone marrow was found to exist in supralethally irradiated (1000-1100 R) C57BL/6 mice and their F1 hybrids, but not in mice of 5 other strains, studied by means of the spleen colony method. The similarities of this phenomenon to the phenomena known variously as “hybrid resistance,” “CFU repression,” or “poor growth phenomenon” suggest that these may all represent different manifestations of a single mechanism.

Potentials of spleen, lymph node, and Peyer's patches to reconstitute lymphoid tissue and produce graft-versus-host reaction.

The capabilities of cells from parental or isogeneic spleen, lymph node, or Peyers patches to repopulate the spleens of sublethally irradiated (C57 X A) F1 hybrid mice were determined. The ability of A cells from the various organs to produce graft-ver-sus-host reaction was assessed. Spleen cell suspensions expressed the capacity to restore -all the spleen components; lymph node suspensions were not competent in restoration of the hematopoietic components, but did restore the lymphoid components. Both the spleen and the lymph node cells from parental strain donors produced severe graft-ver-sus-host reactions. Peyers patch cells from either isogeneic donors or parental strain donors specifically restored the thymus-independent components of lymphoid tissue but did not produce graft-versus-host reactions. These findings are discussed in relation to the thymus-independent nature of the Peyers patches and to the concept of the Peyers patches as the mammalian equivalent to the fowl bursa of Fabricius.

Biochemical Properties of a Defective Hamster C-Type Oncornavirus

A noninfectious hamster C-type oncornavirus (D9) associated with a spontaneous hamster lymphoma was characterized. The defective virions contained 70S RNA and the base composition was similar to that of a murine sarcoma-leukemia virus. With both endogenous and added templates, the virions were found to be deficient in DNA polymerase activity. These results suggest that DNA polymerase may be required for D9 infectivity.

Role of Inductive Microenvironments on Hemopoietic (and Lymphoid?) Differentiation, and Role of Thymic Cells in the Eosinophilic Granulocyte Response to Antigen

Hemopoietic spleen colonies arising in lethally irradiated mice repopulated with limited numbers of bone marrow cells have been shown to be clonal in origin (1,2), each arising from a single stem cell or colony forming unit (CFU).