Biomedical subjects

J Lisowski

Publications and source records attributed to J Lisowski.

At least 19 recordsLinked to original sources

PubMed2001

Cognitive effects of Colostral-Val nonapeptide in aged rats.

Colostrinin, a complex of polypeptides derived from sheep colostrum retards the progress of Alzheimer's disease and facilitates acquisition and retrieval of spatial memory in aged rats. Here we investigated the cognitive effects of colostrinin-derived nonapeptide (Colostral-Val nonapeptide, CVNP) in aged rats that demonstrated learning deficits. Administered for 14 days, CVNP did not affect the acquisition of spatial learning or memory retrieval in the Morris water maze. As a result of reversal learning, placebo treated rats shifted searching behavior and swam less in the area of original platform position and more in the area of recent platform position, suggesting formation of the new spatial map. CVNP treated rats did not change the searching pattern and still investigated the area that contained "original" escape platform, suggesting that CVNP treatment delays the extinction of spatial memory. In another experiment, CVNP administered for 8 days did not influence the acquisition of the active avoidance task, but significantly delayed its extinction. The present findings indicate that colostrinin-derived nonapeptide may delay the extinction of long-term memories.

Aging↗

PubMed2001

Towards an understanding of biological role of colostrinin peptides.

The aim of this study was to elucidate the structure and possible function of colostrinin, also known as a proline rich polypeptide (PRP). The molecular weight of colostrinin was originally determined by gel filtration to be 17,200 daltons. In the presence of guanidinum chloride, however, the molecular weight was found to be about 6,000 daltons. Further studies utilizing high-performance liquid chromatography (HPLC) and mass spectroscopy revealed that colostrinin is a complex consisting of many low molecular-weight polypeptides. A total of 32 peptides were isolated from the original colostrinin preparation by HPLC and subjected to the N-terminal sequence analysis. The results of sequence analysis revealed significant homology of the peptides to three protein precursors: annexin, beta-casein, and a hypothetical beta-casein homolog. In addition, the sequence of several peptides showed no significant homology to any specific protein in the current GenBank database. The synthetic peptides of various lengths representing the N-terminal sequence of the colostrinin peptides were made to study some biological effects. Here we report that colostrinin and some of its component peptides are potent inducers of leukocyte proliferation and of certain cytokines. Also, a series of monospecific antibodies were produced in rabbits against the synthetic peptides. The antibodies were used to study the kinetic of antigen reduction in colostrum and mature milk following lambing. A threefold decrease was common for most antigens studied over the period of 72 h. Based on the results of these studies we postulate that colostrinin represents a diverse group of peptides produced in the mammary gland of mammals for the development of the optimal physiologic responses in offspring. Also, it is hoped that the beneficial use of colostrinin in Alzheimer's Disease (AD), recently reported elsewhere, will revive interest in its clinical application for treatment and/or prophylaxis of many age-related disorders.

Amino Acid Sequence↗

PubMed1999

Colostrinin, a polypeptide isolated from early milk, facilitates learning and memory in rats.

Initial observations in humans indicated that colostrinin, a complex of polypeptides derived from the colostrum of sheep, facilitates cognitive functioning in patients with Alzheimer's disease. Its effect on learning and memory in more controlled settings as well as the specificity of these effects were, however, unknown. The present experiments evaluated the effects of colostrinin on spatial learning (Morris water maze) and incidental memory (habituation test) in male Wistar rats of two age groups. Colostrinin, at a dose of 4 microg/rat IP, facilitated acquisition of spatial learning of 13- (aged) but not 3-month-old (young) rats. At the same dose, it improved incidental learning in aged rats, while the dose of 20 microg/rat attenuated it. Colostrinin did not change locomotor activity of rats. Taken together, the present findings indicate that colostrinin may have some beneficial effects on cognitive functioning, particularly in aged subjects. Given the fact that colostrum is the first nutritive agent of neonates, it might be speculated that its peptides may facilitate the early postnatal development of the cerebral neurons and their plasticity.

Aging↗

PubMed1999

[Signal transmission by Fc gamma receptors].

Fc gamma receptors are present on cells involved in the immune response. Although there are many reports concerning the mechanism of interaction of the receptors with the immunoglobulin ligands, expression of the receptors on cells and their effector functions and genes encoding the receptor chains, information concerning Fc gamma R signalling is rather limited. This review presents data on Fc gamma R-mediated signal transduction.

Animals↗

PubMed1999

Colostrinin: a proline-rich polypeptide (PRP) complex isolated from ovine colostrum for treatment of Alzheimer's disease. A double-blind, placebo-controlled study.

A proline-rich polypeptide (PRP) complex, subsequently called Colostrinin, was isolated from ovine colostrum. The complex showed immunomodulatory properties in mice, rats, and chickens, inducing maturation and differentiation of thymocytes. It was recently found that Colostrinin is a cytokine-like factor that acts as an inducer of interferon gamma (IFN-gamma) and other cytokines in human peripheral blood and cord blood leukocyte cultures and has psycho-immuno-enhancing activity in volunteers. These observations prompted us to study the effect of Colostrinin on patients with Alzheimer's disease (AD). Forty six AD patients were divided into 3 groups and randomly assigned to receive orally either Colostrinin (100 microg per tablet, every second day), commercially available bioorganic selenium (100 microg selenium per tablet, every second day) or placebo tablets. One cycle of the treatment lasted 3 weeks and was separated from the next cycle by a 2 week hiatus. Each patient received 10 cycles of treatment during the year of the clinical trial. Outcomes were assessed by psychiatrists blinded to the treatment assignment. Eight of the 15 AD patients treated with Colostrinin improved and in the 7 others the disease had stabilized. In contrast, none of the 31 patients from the selenium or placebo groups with similar mild or moderate AD improved. The administration of selenium promoted stabilization in 13 of the 15 patients, whereas in the placebo group only 8 of the 16 patients were stabilized at the 12 month trials end-evaluation. Colostrinin was found to be a remarkably safe drug. Mild and transient effects were anxiety, stimulation, insomnia, and tiredness. The results obtained showed that oral administration of Colostrinin improves the outcome of AD patients with mild to moderate dementia. The results are very encouraging and deserve further research.

Adjuvants, Immunologic↗

PubMed1998

Interaction of IgG immunoglobulins with the guinea pig peritoneal macrophage Fc gamma receptors. Effect on the association of the receptors with the membrane skeleton and the cytoskeleton.

Binding of ligands to cell surface receptors may induce an interaction of the receptors with the cytoskeleton and/or membrane skeleton and decrease the solubility of the receptors in nonionic detergents. Cytochalasins, reagents affecting the structure of microfilaments, inhibit some cell functions induced by cross-linking of the receptors with ligands. Information concerning the function of the cytoskeleton in insolubilization of Fc gamma receptors (Fc gamma R) and in Fc gamma R-mediated signal transmission is rather limited. The aim of this work was to investigate the effect of binding of homologous (guinea pig IgG1 and IgG2) and heterologous (rabbit IgG) immunoglobulins to guinea pig peritoneal macrophages on association of the macrophage Fc gamma receptors with the membrane skeleton and cytoskeleton. Cross-linking the macrophage Fc gamma receptors with immunoglobulin ligands induced insolubilization of the receptors in nonionic detergents suggesting association of the receptors with the membrane skeleton and the cytoskeleton. The ligands showed differential effects depending on a subclass and origin of the IgG used. The process of association of the Fc gamma receptors with the skeletons was fast and did not depend on temperature. Treatment of insoluble complexes with cytochalasin D, DNAse I or colchicine showed that actin microfilaments and microtubules play a role, at least partially, in insolubilization of the cross-linked macrophage Fc gamma receptors. Inhibition of insolubilization of the macrophage Fc gamma receptors by genistein indicated that tyrosine kinases are involved in the process of insolubilization. The association with the skeletons might be a part of the process of transduction of a signal which depended on the subclass and origin of IgG used and on the type of the Fc gamma receptor.

Actin Cytoskeleton↗

PubMed1998

Effect of colostrinin, an immunomodulatory proline-rich polypeptide from ovine colostrum, on sialidase and beta-galactosidase activities in murine thymocytes.

Colostrinin: a proline-rich polypeptide (PRP) from ovine colostrum and its nonapeptide active fragment (NP) induce maturation and differentiation of murine thymocytes, formation of helper cells from PNAhigh thymocytes and cytotoxic T cells from PNAlow thymocytes. These processes are accompanied by changes in expression of receptors for peanut agglutinin (PNA), PNAhigh thymocytes were transformed into PNAlow cells, and vice versa. It was shown, in various laboratories, that sialyltransferases are involved in the transformation of PNAhigh thymocytes into PNAlow cells. To find out whether the expression of receptors for PNA on murine thymocytes might also be influenced by other enzymes, we decided to study the effect of PRP and NP on sialidase and beta-galactosidase activities in these cells. The results obtained showed that the most of sialidase activity of murine thymocytes is present in the plasma membrane compartments. Both thymocyte subpopulations PNAhigh and PNAlow, showed similar sialidase activity, which was not affected either by PRP or NP. In contrast to sialidases, most of beta-galactosidase activity was present in the cytosol. PNAhigh, thymocytes showed a higher beta-galactosidase activity than PNAlow cells. Incubation of immature, PNAhigh, thymocytes with PRP or NP enhanced the beta-galactosidase activity in these cells. The presented results suggest that sialidases seem not to be involved in modulation of surface sialic acid content during murine thymocyte maturation. On the other hand, stimulation of activity of beta-galactosidase in PNAhigh, immature thymocytes by PRP and NP suggests that beta-galactosidase in murine thymocytes might be involved in transformation of PNAhigh into PNAlow cells.

Adjuvants, Immunologic↗

PubMed1997

Coincidence between spontaneous release of interferon and tumor necrosis factor by colostral leukocytes and the production of a colostrinine by human mammary gland after normal delivery.

We have tentatively identified colostrinines as novel cytokines produced by the mammary gland after delivery and detectable in colostrum. The primary colostrinine, the proline-rich polypeptide, was isolated from ovine colostrum in 1974. It is generally understood that the various factors present in colostrum play a pivotal role in transmitting of passive or active immunity from mother to child. We have found previously that both ovine and human colostrinines are inducers of interferon (IFN) gamma and other cytokines. In this paper, we reported that the leukocytes isolated from human colostrum donated by healthy mothers at 1-9 days after delivery, produced IFNs and tumor necrosis factors (TFNs) spontaneously. The release of IFNs and TNFs coincided with production of a colostrinine that has been isolated from the human colostrum samples and partially characterized. Our results suggest that the maximum production of colostrinine occurs 3 days after delivery. The tolerance (hyporeactivity) of the colostral leukocytes to IFN inducers and the modulation of the TNF response may be the late effects of the colostrinine release.

Breast↗

PubMed1996

Infective endocarditis in injection drug users: importance of human immunodeficiency virus serostatus and degree of immunosuppression.

Human immunodeficiency virus (HIV)-infected patients are at increased risk for serious and recurrent bacterial infections. We hypothesized that the degree of immunosuppression may play an important role in outcomes for HIV-seropositive patients with infective endocarditis (IE). To test our hypothesis, we retrospectively reviewed 144 cases of IE in injection drug users. One hundred two patients with documented HIV status (45 HIV-seropositive patients and 57 HIV-seronegative patients) were included in the analysis. Eleven patients (6 HIV-seropositive patients and 5 HIV-seronegative patients) died in the hospital. Staphylococcus aureus, the most common etiologic pathogen causing IE in our series, was isolated from 32 HIV-seropositive patients (71.1%) and 32 HIV-seronegative patients (56.1%). A clear inverse correlation between mortality rate and CD4 cell count was demonstrated (r = -.625; P < .001). Both univariate and multivariate analyses supported the finding of significantly higher mortality rates among patients with CD4 cell counts of < 200/mm3 than among patients with CD4 cell counts of > 500/mm3 (OR, 14.7; 95% CI, 2.64-81.9).

Adult↗

PubMed1996

Interaction of human erythrocyte glycophorin with immunoglobulins G.

We have found that human glycophorin and asialoglycophorin interacted with human non-immune IgG. To characterize quantitatively the interaction between glycophorin and IgG we elaborated a direct solid-phase radioimmunoassay. We showed that the binding of IgG was reversible and saturable within the range of IgG concentrations used. Glycophorin bound higher amounts of aggregated than non-aggregated immunoglobulins. The apparent association constant for non-aggregated human IgG was 5.45 +/- 0.93 x 10(5) M-1 and 1.13 +/- 0.78 x 10(6) IgG molecules were bound per 1 picogram of the glycophorin. The binding of glycophorin occurs within the F(ab)2 fragment of IgG, mainly.

Asialoglycoproteins↗

PubMed1996

Colostrinine: a proline-rich polypeptide from ovine colostrum is a modest cytokine inducer in human leukocytes.

A proline-rich polypeptide (PRP), now named colostrinine, molecular weight 18,000, was isolated from ovine colostrum and characterized by Janusz, Lisowski et al. The nonapeptide (NP) which is an active fragment of PRP was obtained by chemical synthesis. In mice, PRP has many regulatory effects on the humoral and cellular immune response. The present paper describes PRP as a cytokine inducer. PRP at concentration of 1-100 micrograms/ml was found to induce production of interferon (IFN) and tumor necrosis factor (TNF) in human peripheral blood leukocytes and in whole blood cultures. The effects were dose related. The identified till now cytokines induced by PRP were IFN-gamma and TNF-alpha but many other cytokines may be stimulated also. NP was considerably less active as the cytokine inducer than the natural PRP. Two volunteers given orally once daily for two to three weeks 100 or 200 micrograms PRP in tablets were found to develop the tolerance of IFN induction and had the modified TNF response. Furthermore, the PRP-treated volunteers showed signs of psycho-stimulation. Taken together our observations suggest that ovine PRP is active in humans and may have therapeutic value as an immunostimulant and/or neurotropic cytokine.

Administration, Oral↗

PubMed1995

Guinea pig peritoneal macrophages. Differential effects of lectins on interaction with IgG immunoglobulins.

Guinea pig peritoneal macrophages have on their surface two receptors, one (Fc gamma 1/gamma 2 R) binding both guinea pig IgG1 and IgG2 and the second (Fc gamma 2R) binding only IgG2 immunoglobulins. We have previously shown that treatment of macrophages with neuraminidase or glycosylation inhibitors affects, in a different way, the binding of guinea pig IgG1, IgG2, and rabbit IgG. In the present study we have shown that pretreatment of guinea pig macrophages with lectins (Con A, WGA, and PNA) also has a different effect on the interaction of the cells with IgG. The lectins increased the binding of guinea pig IgG1, whereas rabbit IgG and guinea pig IgG2 were bound with a lower efficiency than in the case of control cells. Since sialic acid residues seem to modulate the activity of receptors and WGA interacts with sialylated oligosaccharides, we determined the IgG-binding characteristics for WGA-pretreated macrophages. We found that the increase in IgG1-binding ability was caused by an increase in the value of Kapp, but the number of IgG-binding sites was lower than in the control cells. In the case of rabbit IgG and guinea pig IgG2 we observed a decrease of both the value of Kapp and the number of IgG-binding sites. WGA did not interact directly with the Fc gamma receptor. The results of our former papers and the different effects of lectins of various specificities described in this paper suggest different positions of Fc gamma 1/gamma 2 and Fc gamma 2R in the plane of the macrophage membrane in respect to various membrane glycoconjugates.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Proline-rich polypeptide (PRP)--an immunomodulatory peptide from ovine colostrum.

The structure and properties of a new immunomodulatory peptide isolated from ovine colostrum are described. PRP acts both in vivo and in vitro, and is not species specific. PRP increases permeability of skin vessels, and causes differentiation of murine thymocytes into functionally active T cells. It can simultaneously change surface markers and function of cells. The polypeptide is able to reduce binding of peanut agglutinin (PNA) to PNA+ thymocytes and to increase the binding of PNA to PNA- cells. PRP is also able to transform cortisone-resistant thymocytes into cortisone-sensitive, and vice versa. The observed changes occurred concomitantly, i.e. changes in binding of PNA were accompanied by changes in resistance to cortisone and in expression of helper or suppressor activity. The fact that changes induced by PRP are reversible after the second exposure of the cells to the polypeptide makes it unique among known immunomodulators. An active nonapeptide fragment: Val-Glu-Ser-Tyr-Val-Pro-Leu-Phe-Pro was isolated from the products of PRP digestion. It shows full spectrum of biological activities of PRP. The sequence-Pro-Leu-Phe- is responsible for the immunological effect of the peptide.

Adjuvants, Immunologic↗

PubMed1992

Binding properties and expression of the Fc gamma receptors on guinea pig peritoneal macrophages treated with inhibitors of glycosylation.

The effect of inhibition of glycosylation in guinea pig peritoneal macrophages on interaction of their surface Fc gamma receptors with guinea pig and rabbit IgG was studied. The inhibitors used were tunicamycin and monensin. The cells treated with tunicamycin incorporated markedly less [3H]mannose, bound less peanut (PNA) and wheat germ (WGA) lectins and showed diminished ability of binding IgG in comparison with control cells. Treatment of the cells with monensin resulted in an increased incorporation of [3H]mannose, increased binding of PNA but a decreased binding of WGA. Monensin affected binding of guinea pig IgG2 and rabbit IgG to macrophages and had no effect on guinea pig IgG1 binding. Analysis of binding parameters showed that although the number of IgG-binding sites on treated cells was significantly lower, especially in the case of tunicamycin, the apparent association constants were 2-4 times higher than in control cells. The effect of tunicamycin and monensin on parameters of binding of guinea pig IgG2 or rabbit immunoglobulins was much more pronounced than in the case of binding guinea pig IgG1. The results showed that glycosylation modulates expression and IgG binding ability of the Fc gamma receptors on the surface of guinea pig peritoneal macrophages.

Animals↗

PubMed1991

Effect of glycosylation inhibitors on binding properties of the Fc gamma receptors from guinea pig peritoneal macrophages.

Guinea pig peritoneal macrophages possess on their surfaces receptors for the Fc region of IgG immunoglobulins (Fc gamma R). The cells treated with the glycosylation inhibitors tunicamycin or monensin interacted with IgG with a higher affinity and showed a lower number of IgG-binding sites in comparison with control cells. This indicates that the interaction of IgG with the macrophage Fc gamma receptor depends on the degree of glycosylation of the cell surface glycoconjugates and that glycosylation of the macrophage Fc gamma receptor is important for the expression of the mature form of the receptor.

Animals↗

PubMed1991

Effect of a proline-rich polypeptide (PRP) on the development of hemolytic anemia and survival of New Zealand black (NZB) mice.

PRP, administered intraperitoneally into NZB mice, twice a week, at doses 0.01-1 microgram per mouse, significantly lowered the incidence of positive Coombs' reaction and prolonged the mean age of the mice. The effect of PRP on survival of mice was better when the treatment with PRP started early (in mice showing first signs of the disease). The results suggest that PRP may induce, from a precursor pool of cells, suppressor cells controlling development of the disease. In addition, the data indicate that PRP may have a therapeutical value in treatment of autoimmune disorders, e.g. the juvenile arthritis.

Anemia, Hemolytic, Autoimmune↗

PubMed1990

Shedding of the guinea pig peritoneal macrophage Fc gamma receptor. Effect on apparent association constant and on the number of IgG-binding sites on the cells.

During our studies on the structure and properties of guinea pig peritoneal macrophage Fc gamma receptor we observed that these cells spontaneously release an IgG-binding material into supernatant. Although the shedding was accompanied by a decrease in IgG-binding ability of macrophages, the number of IgG-binding sites/cell before and after shedding was similar. However, macrophages after the shedding interacted with IgG with a lower apparent association constant, Ka. Therefore, we assume that the decrease of IgG-binding ability of cells was an effect of decrease in value of Ka. Experiments with protein synthesis inhibitors showed that the shed receptor is replaced by "de novo" synthesized receptor molecules.

Animals↗

PubMed1989

Cell surface sialic acid affects immunoglobulin binding to macrophages.

We demonstrate that guinea pig peritoneal macrophages pretreated with neuraminidase from Vibrio cholerae bind more 125I-IgG than non-treated cells. Estimation of binding constants (Ka and Bmax) shows that the elevation of binding is the result of an increase in affinity and not in the number of receptors for IgG. The change of affinity is proportional to amounts of sialic acid liberated from the cells by increasing doses of neuraminidase. It is also shown that affinity of interactions of IgG with the macrophage receptor is pH dependent. These results indicate that electrostatic forces are important for IgG binding to the macrophage Fc gamma R. The IgG-Fc gamma R interaction can be modulated by changing the degree of sialylation of the macrophage surface glycoconjugates.

Animals↗