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A Szary

Publications and source records attributed to A Szary.

16 recordsLinked to original sources

Effects of overexpression of growth hormone on T cell activity in transgenic mice.

Growth hormone plays a key role in the maturation and maintenance of the immune response, however, the effects of chronic high circulating concentrations of the hormone on the immune system is poorly understood. Transgenic mice overexpressing bovine growth hormone (b-GH) gene, fused to the rat phosphoenolpyruvate carboxykinase promoter (PEPCK), with very high plasma concentration of heterologous b-GH and their littermate normal siblings were used. Spleen cellularity, percentages of total T lymphocytes, CD4+ and CD8+ cells, ratio of T cell subpopulations, mitogen-induced lymphocyte proliferation and natural killer (NK) cell activity were examined in male transgenic mice and normal littermate mice at 2 and 6 months of age. The number of splenic lymphocytes was greater in transgenic mice than in matched normal littermates at both ages. The NK cell activity was lower in transgenic mice than in the matched normal littermates at both ages, with the lowest values found in older mice. The b-GH transgenic mice had lower percentages of T cells at both ages, however, in young transgenic mice, the percentage of CD4+ cells was reduced while percentage of CD8+ cells was increased in comparison to normal controls. Both basal and mitogen-induced proliferation capacity of splenocytes were reduced in PEPCK-b-GH-25 mice as compared to normal littermates of both ages. Proliferative indexes in response to concanavalin A and phytohemagglutinin were markedly decreased in 6 month old PEPCK-b-GH-25 mice as compared to littermate controls or younger mice. These results indicate that overexpression of b-GH in mice is associated with decreased T cell function and that these abnormalities are age-dependent.

Age Factors↗

Age-related effects of ectopic pituitary transplants on the activation of Ames dwarf mouse lymphocytes in vitro.

Prolactin (PRL), one of the anterior pituitary hormones, has been implicated in the development and maintenance of immune system function. The following experiments were conducted to evaluate age-related effects of PRL on immune system activity in a PRL-deficient mouse model, the Ames dwarf. Two- and ten-month-old dwarf and phenotypically normal male mice were used. Six dwarf mice from each age group received a surgically implanted pituitary (under the kidney capsule) from a normal donor female mouse. Six different dwarfs were similarly operated but had no pituitary graft inserted and will be referred to as sham-operated dwarfs. Three weeks following surgery, spleens were removed from the dwarfs and age-matched normal mice and splenocytes isolated. The two age groups will subsequently be referred to as "3-month-old" and "11-month-old", respectively, The splenocytes were used in mitogen-induced (concanavalin A (Con A); phytohemagglutinin (PHA); lipopolysaccharide (LPS)) proliferation assays, and histopaque isolated lymphocytes were used for T cell surface marker determination. Pituitary grafting increased body weights of dwarf mice although the weights were less than control mice independent of age. A similar pattern was observed for total number of splenocytes per spleen. In young animals, the relative number of splenocytes per gram of body weight increased in pituitary grafted dwarfs reaching values of control mice, whereas much smaller differences were observed in older animals. The relative percentage of CD4+ cells was reduced (P<0.01) in 3-month-old pituitary-grafted mice, compared with sham-operated dwarf mice, while no differences were observed between sham- operated dwarf and normal mice. Pituitary grafting did not affect the numbers of CD8+ cells. In 11-month-old animals, the relative percentages of CD4+ and CD8+ cells were greater (P<0.05) in sham-operated dwarf than in normal mice but not affected by pituitary grafting. At 3 months of age, proliferation of splenocytes in response to Con A was increased (P<0.05) in sham-operated dwarfs and reduced (P<0.05) in pituitary-grafted dwarfs compared with normal mice. In contrast, PHA stimulation of splenocytes was decreased (P<0.05) in sham-operated compared with normal, and was still lower in mice receiving an ectopic pituitary. Substantially different responses were obtained in 11-month-old animals. In response to Con A, splenocytes from sham-operated dwarfs exhibited a reduced (P<0.05) proliferative capacity as compared with normals, and proliferation was increased in pituitary-grafted as compared with sham-operated dwarfs. In the presence of PHA, the proliferative capacity of splenocytes was greater (P<0.05) in sham-operated dwarfs as compared to normals and pituitary grafting normalized this parameter. These results demonstrate differential effects of PRL deficiency (sham-operated dwarfs versus normal) and of PRL replacement (pituitary-grafted versus sham-operated) in young as compared with old dwarf mice on immune system activation.

Age Factors↗

Thymostimulin effects on lymphoid organs in Ames dwarf mice.

This work was undertaken to study the effects of thymostimulin (TP-1) on the immune function in Ames dwarf mice, and to relate these effects to PRL and/or GH deficiency in these animals. Male Ames dwarf mice implanted with pituitaries from normal mice under the kidney capsule, sham-operated dwarf mice and normal immature or adult mice were injected daily for five days with TP-1. In comparison to normal animals, sham-operated dwarf mice had markedly lower body, thymus and spleen weights, as well as a lower number of lymphocytes in the spleen and in the thymus and the natural killer (NK) activity of spleen lymphocytes. Ectopic pituitary transplants produced the expected enhancement of body weight gain and increased spleen and thymus weights, which reached the values found in normal (non-dwarf) animals. The numbers of lymphocytes in the spleen and thymus were significantly increased in pituitary-grafted dwarf mice, but the grafts did not modify the cytotoxic activity of NK spleen cells, or the number of peripheral white blood cells (PWBC). In sham-operated dwarf mice, TP-1 treatment did not modify the number of cells in the spleen and thymus, or the NK activity. In pituitary-grafted dwarf mice, treatment with TP-1 induced an increase in the number of spleen lymphocytes and in the NK activity of spleen cells without affecting the weight of lymphoid organs or the number of thymic cells. Plasma prolactin (PRL) and growth hormone (GH) levels of pituitary-grafted dwarf mice were not changed after TP-1 administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

Changes in lymphoid organs of Ames dwarf mice after treatment with growth hormone, prolactin or ectopic pituitary transplants.

This study was performed to obtain more insight into the roles of PRL and GH in the control of immune functions in hereditary dwarf mice characterized by severe immunodeficiency. Adult female Ames dwarf mice (df/df) were injected daily for 10 days with ovine PRL (oPRL), bovine GH (bGH), oPRL+bGH or were implanted with a normal pituitary under the kidney capsule for 5 days. Only the treatment with bGH resulted in significant increases in the gain of body weight, and in absolute and relative thymus and spleen weights. Treatment with oPRL alone did not affect body weight gain or thymus and spleen weights. Treatment with oPRL+bGH produced a significant increase in the gain of body weight and in absolute and relative spleen weight but these effects were smaller than those measured in dwarf mice treated with bGH alone. Only bGH therapy resulted in extensive recovery of the absolute number of lymphocytes in the thymus and spleen of dwarf mice, with the values in treated dwarf mice not significantly different from those found in normal non-dwarf females. However, when these values were corrected for body weight, both the splenic and the thymic indices exceeded the values found in normal mice. The absolute numbers of lymphocytes in the spleen were also increased by oPRL+bGH treatment, but did not reach the values found in normal mice; however, the splenic index exceeded the values found in normal animals. Surprisingly, the absolute and relative numbers of lymphocytes found in the thymus of dwarf mice under oPRL+bGH therapy were indistinguishable from those found in oPRL or vehicle treated dwarf mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Ectopic pituitary transplants restore immunocompetence in Ames dwarf mice.

This work was undertaken to study the effects of prolactin on immune function in Ames dwarf mice. For that purpose, adult Ames dwarf mice were implanted with pituitaries from normal mice under the kidney capsule. Ectopic pituitary transplants produced the expected increase in plasma prolactin levels in male and female dwarf mice as compared to sham-operated dwarf or untreated normal mice. Body weight was significantly increased in pituitary-grafted dwarf mice of both sexes, but did not reach the values found in normal (non-dwarf) animals. Pituitary transplants induced an increase in thymus weight and in the number of lymphocytes in the thymus in dwarf mice of both sexes as compared to sham-operated dwarf controls. The weight of the thymus in grafted dwarf mice remained below values found in normal mice, while the number of thymic lymphocytes became indistinguishable from those recorded in normal mice. Effects of pituitary transplants on the spleen were similar to those described for the thymus; however, neither the weight nor the lymphocyte number in pituitary-grafted dwarfs reached the values found in normal animals. Natural killer activity of spleen lymphocytes from pituitary-grafted male and female dwarf mice was greatly enhanced as compared to lymphocytes from sham-operated dwarfs. This effect was greater in males than in females. The number of white blood cells in pituitary-grafted male dwarf mice was increased and indistinguishable from the values found in normal males. Surprisingly, this effect was absent in the females. These findings suggest that hormones secreted by the transplants, most likely prolactin and growth hormone, can enhance the immune response. This action may be mediated by direct action of prolactin and/or growth hormone on immune cells or by indirect effects.

Animals↗

Measurement of natural killer activity and target cell binding by mouse metrial gland cells isolated by enzymic or mechanical methods.

Cells of the metrial glands of mice were isolated by enzymic or mechanical dissociation procedures. Morphological observations indicated that up to half of the enzymically dissociated cells and nearly all of the mechanically dissociated cells were granulated metrial gland cells, but the presence of some fibroblast-like stromal cells among the latter population was not ruled out. Moreover, the granulated metrial gland cells had lost a substantial part of their granule content during isolation. Both cell preparations had little or no natural killer (NK) activity, indicating either that granulated metrial gland cells are not NK-like or that their NK activity was impaired by loss of granule-associated lytic substances or by other factors. Enzymically dissociated metrial gland cells did not bind significantly to the NK target cell YAC-1, nor did they develop granules, NK activity, or the ability to bind YAC-1 cells during culture in vitro, either in normal medium or with the addition of indomethacin or lymphokines. Mechanically dissociated metrial gland cells bound avidly to YAC-1 cells but not to P815 cells or adult thymus cells, which are not NK target cells. Since many if not most of the mechanically dissociated metrial gland cells appeared morphologically to be granulated metrial gland cells, their selective binding to an NK target cell suggests that granulated metrial gland cells may be related in some way to NK cells.

Animals↗

Effect of pregnancy on the activity of hematopoietic stem cells.

Effect of allogenic and syngenic pregnancy on the activity of multifunctional hematopoietic stem cells of bone marrow and spleen was studied. It was observed that bone marrow of mice mated syngenically and allogenically was more capable of restoring hematopoiesis in lethally irradiated recipients as compared to the bone marrow of nonpregnant mice. Increased number of colony forming hematopoietic cells (CFU-S) was recorded also in the spleen of female mice with syngenic pregnancy. When the spleen of pregnant mice mated allogenically, was the source of the multifunctional hematopoietic spleen cells, the animals displayed suppressed capability to restore hematopoiesis which manifested by a decreased number of CFU-S. Splenectomy appeared to have no influence upon the number of CFU-S in the bone marrow of pregnant mice mated allogenically.

Animals↗

Pharmacological studies on p-chlorophenylamide of 3-methyl-5-benzoylaminoizothiazole-4-carboxylic acid (compound ITCL) the preparation of eventual anti-inflammatory effect.

Pharmacological activity of p-chlorophenylamide of 3-methyl-5-benzoylaminoizothiazole-4-carboxylic acid (compound ITCl) was studied with special regard to its anti-inflammatory effect. Compound ITCl is moderately toxic with no distinct circulatory and central effect. On the other hand, it shows strong anti-inflammatory activity in many tests of immunologically specific, nonspecific and infectious inflammations. The greatest efficacy of the compound was noted in the therapy of experimental, immunologically non-specific (xylene, carrageenin and cotton-test) inflammations. Weaker and less regular therapeutic effect was noted in the cases of immunologic inflammations -- mainly in contact reaction to dinitrochlorobenzene. Compound ITCl was ineffective in relation to transplantation barrier. Therapeutic efficacy of the compound was not observed in herpetic inflammation of the skin. On the other hand, a promising therapeutic effect was noticed in relation to cow-pox virus keratitis. Compound ITCl is well tolerated. It shows no toxic effect on white and red blood cells system in a 4-week exposition. Compound ITCl stabilizes cell membranes. Practical aspect of the obtained results was discussed.

Animals↗

Studies on the experimental therapy of iridocyclitis.

Effectiveness of selected anti-inflammatory drugs on the experimental model of uveitis was evaluated. Studies on the biochemical parameters of inflammation in the aqueous humor and biomicroscopic evaluation of the clinical condition of the anterior chamber of the eye, carried out in the therapy course, allowed to establish the following order of the studied drugs, according to their therapeutical effectiveness (from the most effective): indomethacin greater than ibuprofen greater than hydrocortizone greater than 6-mercaptopurine.

Animals↗

Prostaglandins in carrageenin-induced iridocyclitis.

In a model based on carrageenin-induced inflammation of the anterior eye chamber, prostaglandins and pronounced cellular infiltration appeared in the aqueous humor after six hours. The findings are discussed taking into account various sources of prostaglandins in the course of iridocyclitis.

Animals↗

Studies on the course and therapy of the immunological and the nonspecific iridocyclitis in rabbits.

The immune and carrageenin-induced models of iridocyclitis were elaborated. Characteristics of the dynamics and kinetics of the studied inflammatory processes were conducted on the basis of biochemical indices and of biomicroscopic observations of the anterior chamber of the eye. Evaluation of usefulness of the elaborated models of the uveitis for characterization of the therapeutic effectiveness of the drugs was based on the known antiinflammatory drugs.

Animals↗

The course of carrageenin-induced iridocyclitis in rabbits.

On the basis of biochemical indices in the aqueous humor of the eye strictly related to intensity of inflammation, and morphologic observations with the slit-lamp microscope, dynamics of experimental carrageenin-induced inflammation of the anterior chamber of the eye was studied. Carrageenin-induced inflammation was characterized by intensity of changes in the aqueous humor within a few hours after infection of the inflammatory factor. Peak intensity of the disease process was observed six hours after administration of the inflammatory factor. Protein levels, seromucoid, sialic acid and proteolytic activity in the aqueous humor were correlated with intensity of clinical symptoms observed with the slit lamp. Carrageenin-induced inflammation of the anterior chamber of the eye is an entirely local reaction since the blood serum showed no significant abnormalities of the parameters that were studied. This model, based on biochemical and biomicroscopic studies, may prove useful in the studies of the dynamics of inflammation of the anterior chamber of the eye and for evaluation of anti-inflammatory drugs used in ophthalmology.

Animals↗

[Prostaglandins].

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Animals↗