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M R Simon

Publications and source records attributed to M R Simon.

At least 37 records · Page 2Linked to original sources

Angiotensin II suppression of human mononuclear cell reactivity is associated with enhanced OKT8+ lymphocyte thymidine incorporation.

Recent evidence suggests that angiotensin II may participate in the regulation of inflammation. We previously reported that angiotensin II inhibits human peripheral blood mononuclear cell reactivity and acts directly on lymphocytes. These observations are again confirmed. In addition, purified OKT8+ but not OKT4+ T cell suspensions stimulated with phytohemagglutinin revealed increased thymidine incorporation when simultaneously cultured for 48 hours with angiotensin II. These findings suggest that angiotensin II may inhibit mononuclear cell thymidine uptake through stimulation of suppressor lymphocytes contained within the OKT8+ subpopulation.

Angiotensin II↗

Serum antibodies from patients with Crohn's disease and from their household members react with murine lymphomas induced by Crohn's disease tissue filtrates.

Injection into athymic nude mice (nu/nu) of filtrates of Crohn's disease tissue produces lymphoid hyperplasia and lymphomas, which react with serum antibody from other patients with Crohn's disease. We examined for such antibodies in sera of 14 patients with Crohn's disease and 25 of their household members and compared results with sera from 36 healthy unselected controls and from 14 patients with ulcerative colitis and 19 of their household members. Sera from all patients with Crohn's disease and ulcerative colitis and household members were collected in Michigan, coded, and examined by an indirect immunofluorescence assay against two primary nu/nu lymphomas and one transmitted lymphoma produced by three Crohn's disease tissue filtrates. Seven patients with Crohn's disease had antibodies against antigen(s) in the Crohn's disease lymphomas. Seven household members of patients with Crohn's disease and no household members of patients with ulcerative colitis (P less than 0.05) reacted with Crohn's disease lymphomas. However, none of the patients with ulcerative colitis (P less than 0.01) and no control healthy subjects (P less than 0.005) demonstrated immunoreactivity against nu/nu lymphomas. None of the sera reacted with a control nu/nu lymphoma. Five household members who had positive assay results were first-degree blood relatives, and the other two were spouses of patients with Crohn's disease. These results suggest that a common environmental factor may be associated with Crohn's disease, that there is a familial association in Crohn's disease, and that nu/nu mice are an important model to study the pathogenesis of Crohn's disease.

Adult↗

Effects of simulated increases in body weight on the growth of limb bones in hypophysectomized rats.

The purpose of this study was to subject groups of hypophysectomized male and female rats each to a simulated specific 10% increase in body weight, to a maximum of a doubling of body weight, in order to study the effects of quantified, increased, intermittent, compressive forces on limb bone growth. Chronic centrifugation was employed. 21-day-old Sprague-Dawley rats were used. After 60 days of centrifugation, the rats were sacrificed. The humerus, radius, ulna, femur and tibia were removed from each animal, cleared of all soft tissues, and the bone lengths measured on Helios calipers with an accuracy of 1/20 mm. The data were corrected for differences due to individual body weight by dividing bone lengths by the cube root of the body weight of the same animal. Tukey's studentized multiple-range test was performed to identify aggregations (sets) of force groups between which there are significant differences. The data suggest that the simulated increases in body weight, within the range used for this study, enhance bone growth in hypophysectomized female and male rats similarly - hypophysectomy being a condition known to inhibit bone growth.

Animals↗

Bone mineral content of limb bones of male weanling rats subjected to 30 and 60 days of simulated increases in body weight.

The purpose of this study was to subject groups of male rats each to a specific 10% simulated increase in body weight, ranging from 1.1 to 2.0 g. Constant centrifugation was employed. After 30 and 60 days, rats were sacrificed and perfused with 10% BNF. The humerus, radius, ulna, femur, and tibia were removed, cleared of all soft tissues, weighed, decalcified with EDTA, and reweighed. Bone mineral content (BMC) was determined using the formula: [(Wu - Wd) divided by Wu] X 100. Tukey's multiple range test was used. The data suggest that male weanling rats subjected to simulated increases in body weight, within the range used in this study, undergo enhanced BMC, a bimodal curve describing the relationship between BMC and simulated increases in body weight.

Animals↗

Effects of simulated increases in body weight from birth on the growth of limb bones in rats.

The purpose of this study was to subject groups of newborn male and female Sprague-Dawley rats each to a specific 10% simulated increase in body weight, to a maximum of a doubling of body weight, to study the effects of quantified, increased, intermittent, compressive forces on limb bone growth. Chronic centrifugation was employed. After 90 days of centrifugation the rats were sacrificed. The humerus, radius, ulna, femur, and tibia were removed from each animal, cleared of all soft tissues, measured and weighed. Tukey's Studentized multiple range test was performed to identify aggregations (sets) of force groups between which there are significant differences. The data suggest that newborn male and female rats subjected to simulated increases in body weight, within the range used for this study, undergo enhanced general body growth and limb bone growth.

Animals↗

The effects of simulated increases in body weight on the developing rat tibia: a histologic study.

Groups of weanling and newborn Sprague-Dawley rats were each subjected to a specific 10% simulated increase in body weight to a maximum of a doubling of body weight, using constant centrifugation, to study the effects of quantified, increased, intermittent, compressive forces on the histomorphology of the proximal tibial epiphysial growth plate. The weanling rats were sacrificed after 30 and 60 days of centrifugation; the newborn rats were sacrificed after 90 days of centrifugation. The results demonstrated no prominent changes in histomorphology, when compared to the controls, in the weanling rats sacrificed at 30 days of centrifugation, or in newborn rats subjected to 90 days of centrifugation; however, a prominent thinning of the growth plates was observed in the weanling rats sacrificed at 60 days of centrifugation.

Animals↗

The effect of angiotensin II on human mononuclear cell reactivity: suppression of PHA-P-induced thymidine incorporation.

Recent evidence suggests that angiotensin II may participate in the regulation of inflammation. We therefore studied the effects of angiotension II on human peripheral blood mononuclear cell reactivity. Peripheral blood mononuclear cell suspensions stimulated with PHA-P revealed decreased thymidine incorporation when simultaneously cultured for 48 or 72 hours with angiotensin II. Experiments were next conducted to determine whether angiotensin II acted directly on lymphocytes. Complete monocyte depletion (greater than 99.5%) resulted in low PHA-P-induced reactivity which was still inhibited by the addition of angiotensin II. Purified (greater than 99.5%) lymphocytes incubated with angiotensin II prior to reconstitution of mixed mononuclear cell suspensions led to reduced PHA-P-stimulated thymidine incorporation. These findings suggest that angiotensin II can effect mononuclear cell uptake possibly through actions on the lymphocyte population.

Adult↗

Angiotensin II inhibition of mitogen- and antigen-induced human blood mononuclear cell thymidine uptake.

Angiotensin-converting enzyme and other components of the angiotensin system may participate in the regulation of inflammation. We therefore studied the effects of angiotensin II on human mononuclear cell reactivity. 48 hr phytohemagglutinin (5 micrograms/ml)-stimulated cultures of mononuclear cells from 6 subjects revealed thymidine uptake of 84,525 +/- 18,923 cpm (mean +/- se). When cultures contained angiotensin II (10(-7) M), reactivity was decreased to 75,279 +/- 17,727 cpm (p less than 0.05, paired t-test). Depletion of monocytes by nylon wool filtration or Percoll density-gradient centrifugation revealed persistence of the effect. Tetanus toxoid (0.5 LfU/ml)-induced thymidine uptake (86,910 +/- 31,591 cpm) was also reduced by the presence of 10(-6) M angiotensin II (68,094 +/- 25,509 cpm, p less than 0.01, paired t-test) when angiotensin II was added on the fourth day of 5 day cultures. No angiotensin II effects were observed on unstimulated thymidine incorporation. These findings indicate that angiotensin II can inhibit antigen- and mitogen-induced mononuclear cell reactivity and suggest that angiotensin II, the product of angiotensin converting enzyme may be an inhibitor of human lymphocyte function.

Angiotensin II↗

The effects of simulated increases in body weight for 30 and 60 days on bone robusticity of limb bones in rats.

The purpose of this study was to subject groups of weanling male rats each to a specific 10% simulated increase in body weight, ranging from 1.1G-2.0G, using constant centrifugation. (In this paper, "G" is the acceleration due to gravity.) After 30 and 60 days, rats were killed and perfused with 10% buffered neutral formalin (B.N.F.). The humerus, radius, ulna, femur, and tibia were removed, cleared of all soft tissues, weighed, and the total length measured. Bone robusticity was calculated using the ponderal index: bone length/3 square root bone weight. Tukey's Multiple Range Test was used. The data suggest that the specific limb bone, G, and duration of centrifugation are each factors in the response of limb bones to simulated increases in body weight.

Animals↗

The effects of simulated increases in body weight for 60 days on robusticity and mineral content of limb bones of hypophysectomized rats.

The purpose of this investigation was to subject separate male and female groups of weanling hypophysectomized rats each to a specific 10% simulated increase in body weight using constant centrifugation, ranging from 1.1G to 2.0G, to study changes in bone robusticity and bone mineral content. (In this paper, "G" is the acceleration due to gravity.) After 60 days of centrifugation at 24 rpm, the rats were killed and the humerus, radius, ulna, femur, and tibia were removed, cleared of soft tissues, weighed, measured, decalcified with EDTA, and reweighed. Bone robusticity was determined using the ponderal index: P.I. = bone length divided by 3 square root bone weight; and bone mineral content (BMC) was determined using the formula: BMC = [(Wu - Wd) divided by Wu] X 100. Tukey's Studentized Multiple Range T Test was used. The data suggest that, for both male and female hypophysectomized rats, bone robusticity is decreased with simulated increases in body weight; also, for males, a bimodal curve describing the relationship between BMC and simulated increases in body weight is suggested.

Animals↗

The effects of simulated increases in body weight from birth on bone robusticity of limb bones of rats.

Groups of newborn rats were each subjected to a specific 10% simulated increase in body weight, ranging from 1.1G to 2.0G, to study changes in bone robusticity. (In this paper, "G" is the acceleration due to gravity.) Constant centrifugation was used. At 90 days of age, the rats were killed and the humerus, radius, ulna, femur, and tibia were removed, weighed, and measured. Bone robusticity was calculated using the ponderal index: bone length/3 square root bone weight. Tukey's Multiple Range Test was used. The data suggest that, for both males and females, bone robusticity is increased with simulated increases in body weight.

Animals↗

Captopril enhances in vitro human lymphocyte thymidine incorporation.

Angiotensin-converting enzyme activity is present in human sarcoid as well as murine schistosome granulomas. Inhibition of angiotensin-converting enzyme by captopril results in decreased granuloma size in animals. Since captopril is used clinically to treat hypertension, its effect on human lymphocyte thymidine incorporation was determined. It was found that 5 X 10(-5) M and 10(-4) M captopril enhances lymphocyte thymidine uptake induced by 25 micrograms/ml phytohaemagglutinin-P. This suggests that captopril can alter immunological reactivity in man and that angiotensin-converting enzyme may have an immunological function.

Captopril↗

The rat as an animal model for the study of senile idiopathic osteoporosis.

Bone robustness of the major limb bones of 2-year-old and 3-year-old male Sprague-Dawley rats was determined and compared to that of 3-month-old male Sprague-Dawley rats. The results were compared to the published data on two different breeds of laboratory rats to ascertain if the laboratory rat is an appropriate animal model for the study of senile idiopathic osteoporosis in humans. The results show that the limb bone that becomes the most osteoporotic is the male Sprague-Dawley tibia. If one were selecting for the most appropriate breed of rat, it would be the Buffalo rat.

Animals↗

The effects of quantified amounts of increased intermittent compressive forces for 30 and 60 days on the growth of limb bones in the rat.

The purpose of this study was to subject groups of rats each to a specific 10% increase in body weight, to a maximum of a doubling of body weight, to study the effects of quantified, increased, intermittent, compressive forces on limb bone growth. Chronic centrifugation was employed. 21-day-old male Sprague-Dawley rats were used. After 30 and 60 days of centrifugation, the rats were killed. The humerus, radius, ulna, femur, and tibia were removed from each animal, cleared of all soft tissues, measured and weighed. The data were corrected for differences due to individual body weight by dividing bone lengths by the cube root of the body weight of the same animal. Tukey's 'Studentized' Multiple Range Test was performed to identify aggregations (sets) of force groups between which there are significant differences. The data suggest that the value of g, together with the amount of time spent at centrifugation, are both significant factors in the effects of increased intermittent, compressive forces, produced by simulated increases in body weight, on limb bone growth.

Animals↗

Effects of experimental hyperadrenocorticism on the growth of the femur and tibia in normal and bipedal rats.

Daily subcutaneous injections of glucocorticoid preparations have been shown to produce clinical signs of hyperadrenocorticism which resulted in interference with the growth of rats, shown by measurements both of body weight and of the length of long bones. The purpose of this study was to see if increased, intermittent, compressive forces, produced by experimental bipedalism, would mitigate the negative effects of cortisone injections on long bone growth and if there would be a difference in reaction between male and female rats. Male and female Sprague-Dawley rats were used for control, cortisone-injected, and cortisone-injected plus bipedal groups. Experimental bipedalism was produced at 10 days of age; cortisone injections began at 30 days of age; all animals were sacrificed at 65 days of age. Tibial and femoral lengths were measured. The results do not support the hypothesis that bipedalism can be instrumental in mitigating the effects of hyperadrenocorticism on hindlimb long bone growth.

Adrenal Cortex Diseases↗

Comparison of cultures of human lymphocytes obtained following NH4Cl induced red blood cell lysis and Ficoll-Hypaque density gradient centrifugation.

Lymphocyte thymidine uptake in leucocytes prepared by NH4Cl induced RBC lysis was compared with that of lymphocytes obtained following Ficoll-Hypaque centrifugation using polynomial regression dose response curves which adjusted for inherent subject variability. Eleven male subjects were studied. Heparinized blood was either layered in Ficoll-Hypaque or treated with 0.87% NH4Cl to induce RBC lysis. Phytohemagglutinin-P (PHA) dose response curves were determined for each subject using triplicate 5 day cultures. For each subject, at each Pha concentration ranging from 12.5 to 167micrograms/ml, triplicate mean cpm of Ficoll-Hypaque treated lymphocytes and NH4Cl treated lymphocytes were compared by the 2 tailed Student's T test. Responses of cultures of NH4Cl treated lymphocytes were significantly different (less than 0.05) from the responses of cultures of Ficoll-Hypaque treated lymphocytes for at least 2 PHA doses in 8 of the 11 subjects. The quadratic dose response curves were also significantly different (p less than 0.05) for 9 of the 11 subjects. A repeated measures quadratic regression was used to determine the best fit dose response curves for each of the experimental conditions. For Ficoll-Hypaque treated lymphocytes, mean cmp=44,977+1400.4 (PHA concentration)-5.90 (PHA concentration)2+ subject effect; s.e.=22,256; for NH4Cl treated lymphocytes, mean cpm=58,039+1022.8(Pha concentration)-5.32 (PHA concentration)2+ subject effect; s.e.=37,966. The p values from the F tests for significance of these quadratic regressions are different, F=1.91, d.f.=30,30; p less than 0.001. The lack of significance of the NH4Cl treated lymphocytes' does response quadratic regression and its larger s.e. indicates that the NH4Cl treated lymphocyte culture dose response curve is less predictable than that of Ficoll-Hypaque treated lymphocytes.

Ammonium Chloride↗

Aluminum ion deposition in rat tissues following implantation of a ceramic-metal disc.

Plasma-sprayed alumina on 316L stainless steel discs was implanted in Sprague-Dawley rats for six months; at which time the animals were sacrificed, and selected tissues analyzed for aluminum concentration using atomic absorption spectrophotometry. The liver, testes, and kidneys exhibited significant increases in aluminum ion concentration.

Aluminum↗