Biomedical subjects
J Padawer
Publications and source records attributed to J Padawer.
Zone II flexor tendon repair: effects of vitamins A, E, beta-carotene.
Ninety-six adult Leghorn chickens each had the flexor profundus tendon in each middle toe sharply divided in Zone II with immediate repair (pentobarbital, ketamine anesthesia). Animals were then randomly assigned to receive unsupplemented standard chick chow or the chow supplemented with vitamin A (150,000 IU/kg chow), Vitamin E (1000 IU/kg chow), or beta-carotene (90 mg/kg chow). Eight animals from each of the four groups were examined at 7, 30, or 45 days post repair. After sacrifice, in situ composite wound breaking strength was measured in the amputated toe by constant speed tensiometry. Vitamin A-supplemented animals demonstrated breaking strength more than double that of control at each postoperative test day, while those animals receiving supplemental Vitamin E had breaking strength less than half that of control at Day 7 and Day 45. These results are statistically significant. Tensiometry curves differed markedly at all time points among the groups: Vitamin A curves being broader, higher, and having more spikes. These differences in the tensiometry curves, both qualitative and quantitative, may be due to differences in intrinsic tendon healing or to differences in adhesion formation or a combination of both. beta-Carotene supplementation had modest effect. We conclude that supplemental dietary vitamin A increases the breaking strength of composite tendon wounds and that supplemental dietary vitamin E decreases it.
Structural alterations in fibroblast monolayers caused by mast cell degranulation.
Populations of mature, long-lived, nondividing mast cells develop on embryonic fibroblast monolayers after 1 mo growth of lymph node cells taken from mice immunized with horse serum. Total mast cell degranulation with 80-90% histamine release has been obtained by monoclonal anti-2,4-dinitrophenol (anti-DNP) IgE and the antigen. This degranulation process was studied by time-lapse cinematography and scanning electron microscopy. Excitation of the mast cells began as early as 10 s after addition of the antigen and lasted for about 15 s. Consequently, the fibroblast cytoplasm was displaced by short 5-10 s movements. Before degranulation, due to an extracellular film that coated the cells and the extracellular fibers, the monolayer appeared as a continuous, uninterrupted layer. After degranulation and fibroblast cytoplasm displacement, the fibrous network was exposed. Several inhibitors and antagonists of mast cell mediators were introduced to the cultures prior to addition of the antigen. So far, only with soybean trypsin inhibitor was the cytoplasm dislocation inhibited. Histamine H1 and H2 and serotonin receptor antagonists, as well as indomethacin, cortisol, aprotinin, and phenylmethylsulfonyl fluoride, did not inhibit. These results suggest that chymase, which constitutes the greater part of the mast cell granule protein, is the causative agent.
Mast cells in rat thalamus: nuclear localization, sex difference and left-right asymmetry.
Mast cells were positively identified in rat brain by a combination of staining and histochemical procedures. These cells stained positively with toluidine blue and Astrablau at low pH, indicating the presence of a proteoglycan similar to that found in peripheral mast cells. Brain mast cells also fluoresced after o-phthalaldehyde exposure, indicating that they contain histamine. Mast cells varied greatly in number among brains, but their distribution was almost exclusively thalamic; within thalamus, the ventral complex, medial dorsal, lateral, and paraventricular nuclei contained the most mast cells. Mast cell numbers were greater in brains of females than of males, and greater in left than in right hemispheres. These findings suggest that mast cells have a specialized function in thalamus and/or that the vascular environment of the thalamus is particularly conducive to mast cell accumulation.
Morbidity and mortality reduction by supplemental vitamin A or beta-carotene in CBA mice given total-body gamma-radiation.
Male CBA mice received graded doses (450-750 rad) of total-body gamma-radiation (TBR) from a dual-beam 137Cs irradiator. Commencing directly after TBR, 2 days later, or 6 days later, groups of mice received supplemental vitamin A (Vit A) or beta-carotene (beta-Car), compounds previously found to reduce radiation disease in mice subjected to partial-body X-irradiation. Given directly after TBR, supplemental Vit A decreased mortality, evidenced by increases in the radiation dose required to kill 50% of the mice within 30 days (LD50/30). In one experiment, Vit A increased the LD50/30 from 555 to 620 rad; in another experiment, Vit A increased the dose from 505 to 630 rad. Similarly, in a third experiment, supplemental beta-Car increased the LD50/30 from 510 to 645 rad. Additionally, each compound increased the survival times, even of those mice that died within 30 days. In addition to reduction of mortality and prolongation of survival time, supplemental Vit A moderated weight loss, adrenal gland hyperemia, thymus involution, and lymphopenia--all signs of radiation toxicity. Delaying the supplementation for 2 days after irradiation did not greatly reduce the efficacy of Vit A; however, delaying supplementation for 6 days decreased its effect almost completely.
Regression of C3HBA mouse tumor due to X-ray therapy combined with supplemental beta-carotene or vitamin A.
Male CBA/J mice, ingesting a vitamin A- and beta-carotene-sufficient laboratory chow, were inoculated in a hind limb with 2 X 10(5) C3HBA adenocarcinoma cells. When the mean tumor size was 6.2 mm, the mice were divided randomly into groups; some groups received supplemental vitamin A or beta-carotene, some received 3,000 rad local radiation to the tumor, and others received both radiation and one of the supplements. All mice that received only radiation or one of the dietary supplements died within 3 months. When local irradiation and supplemental vitamin A or beta-carotene were coupled, "complete" tumor regression occurred in every case (12/12), and tumor regrowth in and death of the mice occurred in only 1 of 12 in each of these groups during the succeeding 12 months. One year after irradiation and dietary supplementation, half the surviving mice were switched back to the control chow. During the next year, none of the mice remaining on the vitamin A or beta-carotene supplements developed tumors; however, of 6 mice switched from vitamin A, 5 had tumors that reappeared. In contrast, tumors recurred in only 2 of 6 mice after they were switched from beta-carotene. A second experiment yielded similar results. These results show that both vitamin A and beta-carotene supplementation added remarkably to the antitumor effect of local irradiation. beta-Carotene supplementation produced a greater residual antitumor action than vitamin A supplementation after the supplements were discontinued, which may have been due to greater tissue storage of beta-carotene.
Cancer control: X-ray induced C3HBA tumor regression and prevention of its regrowth by beta-carotene or vitamin A.
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Increased survival due to radioactive estradiol in mice with C3HBA or BW 10232 tumors.
The influence of progesterone and estradiol labeled with tritium was studied in mice inoculated with transplantable mammary adenocarcinomas C3HBA or BW 10232. Tumor size, tumor growth rate, and host survival were measured. Radioactive [3H]estradiol administration increased survival time and inhibited tumor growth in mice inoculated with these tumor lines. Tumor growth retardation depended on the amount of radioactivity injected and nonradioactive estradiol was without any salutary effect on tumor size or host survival. Neither survival times nor tumor growth rate were altered by radioactive [3H]progesterone. The underlying mechanism(s) is (are) referable to ionizing radiation by the specific carrier estradiol or to an isotope effect of [3H]estradiol.
Moloney murine sarcoma virus tumors in CBA/J mice: chemopreventive and chemotherapeutic actions of supplemental beta-carotene.
Decreased tumor frequency, increased latent period, and increased rate of tumor regression were observed in male inbred CBA/J mice fed supplemental beta-carotene before and/or after they were inoculated with the Moloney sarcoma virus. When beta-carotene feeding was begun after tumors were already present, it markedly increased the rate of tumor regression. beta-Carotene minimized the virus-induced thymus gland involution that accompanies tumor growth, and this action on the thymus gland was believed to underlie part of beta-carotene's antitumor activity. The basal diet, a standard commercial mouse chow containing more vitamin A than the National Research Council recommends as a daily allowance for rodents, supported normal growth, reproduction, and longevity of normal mice. The work reported here is the first demonstration of the antitumor action of beta-carotene in mice inoculated with an oncogenic virus.
Diagnostic ultrasound time-lapse and transmission electron microscopic studies of cells insonated in vitro.
A fibroblast cell line (3T3) and normal rat peritoneal fluid cells were exposed in vitro to pulsed ultrasound from a diagnostic instrument (Smith-Kline "Ekoline 20"). We report here on ultrastructural changes in both cell types and on altered motility patterns in 3T3 fibroblasts. Abnormal motility was detectable 10 generations after exposure. X-irradiation and ultraviolet light elicited similar effects on cell motion. It is suggested that the cellular effects of diagnostic levels of ultrasound be further examined both in vitro and in vivo.
Combined treatment with radioestradiol-lucanthone in mouse C3HBA mammary adenocarcinoma and with estradiol-lucanthone in an estrogen bioassay.
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Impaired wound healing in streptozotocin diabetes. Prevention by supplemental vitamin A.
Goodson and Hunt showed that wound healing is impaired in streptozotocin (Sz) diabetic rats; we speculated that this impairment results from defective early inflammatory responses to wounding. Because we had shown that supplemental vitamin A stimulates the early inflammatory response to wounding in nondiabetic rats, we studied the effect of supplemental vitamin A on wound healing in rats with Sz-induced diabetes. Male Sprague-Dawley rats were fed a commercial rat chow containing twice the amount of vitamin A recommended by the NRC for healthy rats. The rats ate and drank (tap water) ad libitum. Two-thirds of the rats were injected (intravenously) with Sz 60 mg/kg body weight. All of these rats became diabetic (hyperglycemia greater than 350 mg/dl, hyperphagic, polydipsic, polyuric, glycosuric greater than 2%). Seven days later, half of the Sz-injected rats were continued on the chow (Group 2) while the other half (Group 3) were switched to the chow supplemented with 150,000 units of vitamin A/kg chow. The next day, all were wounded (7 cm skin incisions and s.c. polyvinyl alcohol sponge implants). Similarly wounded saline injected nondiabetic rats ingesting the unsupplemented chow served as controls (Group 1). The wounds of Group 2 rats healed poorly compared to Group 1 (breaking strength of skin incisions, 308 +/- 19 g vs 584 +/- 23 g, p less than 0.001; hydroxyproline of the sponge reparative tissue, 0.87 mg vs 2.40 mg/100 mg sponge p less than 0.001). Supplemental vitamin A (Group 3) did not affect the hyperglycemia, hyperphagia, polydipsia or glycosuria, but increased the breaking strengths of the incisions of the diabetic rats (468 +/- 40 g, p less than 0.001), and the sponge hydroxyproline (2.38 mg/100 mg sponge, p less than 0.001). In another experiment, in which the wounding and start of supplemental vitamin A were delayed until 28 days after streptozotocin administration (50 mg/kg body weight), similar results were obtained. Streptozotocin diabetes also caused a decrease in the cross-linking of reparative collagen as judged by the ratio of breaking strengths of skin incisions before and after formalin fixation. Supplemental vitamin A did not influence this defect. Sz also caused peripheral lymphocytopenia, adrenal hypertrophy and thymic involution which responded to the supplemental vitamin A. Based upon experimental data and theoretical considerations we conclude Sz diabetes causes two defects in wound healing: a) quantitatively (reduction in reparative collagen accumulation) and b) qualitative reduction in the degree of cross-linking of reparative wound collagen. The action of supplemental vitamin A in correcting the impaired wound healing, adrenal enlargement, thymic involution and lymphocytopenia of Sz-diabetic rats is independent of an effect on their disturbed carbohydrate metabolism.
Stimulation of liver regeneration by clofibrate.
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Antipyretic and antiviral action of vitamin A in Moloney sarcoma virus- and poxvirus-inoculated mice.
Six week-old male CBA/J mice fed a commercial powdered laboratory chow or the same chow supplemented with vitamin A palmitate (150,000 U/kg) were inoculated with either the Moloney strain of murine sarcoma virus (M-MuSV) or poxvirus. Central body temperature was measured daily. Both viruses elicited fevers, but the fevers were less pronounced and of shorter duration in the mice ingesting the vitamin A-supplemented diet. Palpable M-MuSV-induced tumors appeared later, were less frequent, grew more slowly, and were resorbed sooner in the mice fed the vitamin A supplement. Similarly, in these mice the appearance of pox lesions was delayed, their numbers reduced, and their disappearance hastened.
Inhibition of tumor growth by metyrapone and desoxycorticosterone.
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Scanning electron microscopy: identification of mast cells by indirect cathodoluminescence.
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Editorial: The ins and outs of mast cell function.
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Mast cells: extended lifespan and lack of granule turnover under normal in vivo conditions.
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