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M Majewski

Publications and source records attributed to M Majewski.

At least 37 records · Page 2Linked to original sources
PubMed2001

Distribution of growth associated protein (GAP-43) immunoreactivity in nerve fibers supplying the pig pineal gland.

An immunohistochemical study of the pig pineal gland was carried out using monoclonal mouse antiserum against growth-associated protein GAP-43. The pineal glands were obtained from the 3, 5, 8 weeks old piglets. The immunopositive nerve fibers were observed in the pineal gland as well as in the habenular and the posterior comissural areas. They formed a dense network in the habenular area and the proximal part of the pineal gland. In the comissural area and in the apical part of the gland. single positive fibers were observed. The obtained results may suggest a difference in the plasticity of innervation between the particular regions of the pineal gland.

Animals↗
PubMed2000

Aldol addition of lithium and boron enolates of 1,3-dioxan-5-ones to aldehydes. A new entry into monosaccharide derivatives

Methods allowing control of stereoselectivity in aldol reactions of enolates derived from 1,3-dioxan-5-ones (4) are described. Boron enolates, generated in situ, react with benzaldehyde to give the corresponding anti aldol selectively (the anti:syn ratio of up to 96:4) and in high yield. Lithium enolates give high anti selectivity only with aldehydes branched at the alpha-position. Enantioselective deprotonation of C(S) symmetrical dioxanones (e.g., 4b) can be accomplished efficiently, with enantiomeric excess of up to 90%, with chiral lithium amide bases of general structure PhCH(Me)N(Li)R (9, 10) if the R group is sufficiently bulky (e.g, R = adamantyl) or is fluorinated (e.g., R = CH2CF3). Dioxanone boron and lithium enolates react readily with glyceraldehyde derivatives (19), yielding protected ketohexoses (20 and 21).

Journal Article↗
PubMed2000

The immunosuppressive macrolide RAD inhibits growth of human Epstein-Barr virus-transformed B lymphocytes in vitro and in vivo: A potential approach to prevention and treatment of posttransplant lymphoproliferative disorders.

Whereas the standard immunosuppressive agents foster development of posttransplant lymphoproliferative disorders (PTLDs), the impact of RAD, a macrolide with potent immunosuppressive properties, and other immunosuppressive macrolides on these disorders remains undetermined. We found that RAD had a profound inhibitory effect on in vitro growth of six different PTLD-like Epstein-Barr virus+ lymphoblastoid B cell lines. Similar to normal T cells, RAD blocked cell-cycle progression in PTLD-like B cells in the early (G(0)/G(1)) phase. Furthermore, RAD increased the apoptotic rate in such cells. The drug also had a profound inhibitory effect on the growth of PTLD-like Epstein-Barr virus+ B cells xenotransplanted s.c. into SCID mice. The degree of the RAD effect varied among the three B cell lines tested and was proportional to its effects on the cell lines in vitro. In this in vivo xenotransplant model, RAD markedly delayed growth or induced regression of the established tumors. In one line, it was able to eradicate the tumor in four of eight mice. When RAD treatment was initiated before tumor cell injection, a marked inhibition of tumor growth was seen in all three lines. In two of them, the drug prevented tumor establishment in approximately 50% of mice (5/11 and 5/8). In summary, RAD is a potent inhibitor of PTLD-like cells in vitro and in vivo. These findings indicate that, in contrast to the standard immunosuppressive agents, macrolides such as RAD may be effective in prevention and treatment of PTLDs.

Animals↗
PubMed2000

[Achilles tendon rupture. A prospective study assessing various treatment possibilities].

The object of this study was to compare treatment of ruptured Achilles tendon by operative "end to end" surgery, percutaneous repair, or conservative therapy clinically; a subject of considerable controversy in the literature. These three methods were compared in 73 patients in a randomized trial between 1994 and 1996. After 2.5 years (11-41 months), the actual activities were assigned to the Hannover Achilles tendon score and the ability of doing work or sport activities was assessed. After this period, 59.3% of the patients showed good and excellent results on the Achilles tendon score, with over 79 points (open surgery 59.1%, percutaneous 60%, conservative treatment 58.3%). None of the patients reached the maximum score of 100 points. During the isometric strength tests, the patients with percutaneous repair had a lower weakening of the treated leg (8.9%) compared to the open-operated (12.7%) and non-operated patients (17.8%). Of the patients who had percutaneous surgery, 88% rated their treatment as good or excellent; those who had open surgery 77.3%, and those with conservative treatment 75%. The percutaneous group were able to resume work and sport much sooner than the other two groups. Bearing in mind the literature and these results, we have developed an algorithm for treating Achilles tendon rupture to assist decision making in daily routine. In this way, the use of percutaneous Achilles tendon repair can be carried out in most of cases.

Achilles Tendon↗
PubMed1999

Activation of mitochondrial Raf-1 is involved in the antiapoptotic effects of Akt.

The Akt serine/threonine kinase is required for the survival of many cell types and for transformation of hematopoietic cells by the BCR/ABL oncogenic tyrosine kinase. Analysis of the potential mechanisms whereby Akt promotes survival of hematopoietic cells revealed that it induced the activity of plasma membrane and mitochondrial Raf-1 in a Ras-independent, but PKC-dependent manner. Inhibition of plasma membrane Raf-1-dependent mitogen-activated protein kinase activity had no effect on the enhanced survival of cells expressing Akt. By contrast, suppression of mitochondrial Raf-1 enzymatic activity by expression of a mitochondria-targeted Raf-1 dominant-negative mutant rendered Akt-expressing cells susceptible to apoptosis induced by growth factor deprivation and was accompanied by inhibition of BAD, but not mitogen-activated protein kinase, phosphorylation. Together, these data indicate that PKC-dependent activation of Raf-1 plays an important role in Akt-dependent antiapoptotic effects.

Animals↗
PubMed1999

Immunohistochemical properties of nerve fibres supplying accessory male genital glands in the pig. A colocalisation study.

Immunohistochemical studies have been performed to investigate the occurrence and coexistence of two catecholamine-synthesising enzymes, tyrosine hydroxylase and dopamine-beta-hydroxylase, and several neuropeptides, including neuropeptide Y, vasoactive intestinal polypeptide, Leu5-enkephalin, somatostatin, calcitonin gene-related peptide and substance P, in nerve fibres supplying porcine accessory genital glands, the seminal vesicles, prostate (body and the disseminated part) and bulbourethral glands. Three major populations of nerve fibres supplying non-vascular elements of the glands have been distinguished (from the largest to the smallest one): (1) noradrenergic fibres, the majority of which contain Leu5-enkephalin, neuropeptide Y or, to a lesser extent, somatostatin, (2) non-noradrenergic, putative cholinergic fibres containing vasoactive intestinal polypeptide, neuropeptide Y and/or somatostatin and, (3) nonnoradrenergic, presumably sensory fibres, containing calcitonin gene-related peptide and substance P. Whilst the coexistence patterns within nerves supplying particular glands are similar, the density of innervation varies between the organs. The innervation of the seminal vesicles and prostatic body is more developed than that of the disseminated part of the prostate and bulbourethral glands. The majority of noradrenergic fibres related to blood vessels contain neuropeptide Y only, while the non-noradrenergic nerves contain mainly vasoactive intestinal polypeptide. The possible function and origin of particular nerve fibre populations are discussed.

Animals↗
PubMed1999

Innervation of the fibro-elastic type of the penis: an immunohistochemical study in the male pig.

The occurrence and colocalization of several biologically active neuropeptides, catecholamine-, acetylcholine- or nitric oxide-synthesizing enzymes-tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (D beta H), choline acetyl-transferase (ChAT) and nitric oxide synthase (NOS I), respectively, as well as the vesicular acetylcholine transporter (VAChT) were investigated in the penile glans (GP), corpus and crura (CP), as well as in the retractor penis muscle (RPM) of juvenile and adult boars. Immunohistochemistry revealed that nerves immunoreactive (IR) to TH, D beta H, vasoactive intestinal polypeptide (VIP) and somatostatin (SOM) were the most numerous, followed (in decreasing order of density) by nerves IR to NOS, neuropeptide Y (NPY), substance P (SP), calcitonin gene-related peptide (CGRP), galanin (GAL), Leu5-enkephalin (LENK) and ChAT/VAChT. The CP contained the largest number of nerve fibres followed by the RPM, GP and corpus. Enzyme/peptide-containing nerves were associated with both the vascular and non-vascular penile structures. However, differences existed for their density and intrapenile distribution. Nerve terminals IR for different combinations of VIP, GAL or SOM were more frequent than those IR for NOS or CGRP in the non-vascular penile structures while the vasculature and the RPM received a prominent TH/D beta H-, VIP-, SOM- or NOS-IR nerve input. The present data indicate that the porcine penis receives nerve fibres that exhibit diverse chemical codes and that differences in the chemical coding of the nerve fibres may depend on their penile target-structure.

Age Factors↗
PubMed1999

Synaptogenesis and structure of the autonomic ganglia.

The present study summarises the current data dealing with processes leading to the establishing of the synaptic architecture and connections with both the preganglionic neurons and target tissues of autonomic ganglia Starting from the migration point of the neural crest cells, the factors and mechanisms driving the development of the autonomic nervous system, axonal pathfinding and establishing of ganglionic connections, as well as formation and plasticity of autonomic synapses are reviewed with regard to their functional relevance in these processes. Furthermore, the chemical neuroanatomy and somatotopic arrangement of either the preganglionic, sympathetic or parasympathetic division of the autonomic nervous system are discussed from the morphological ¿and functional point of view.

Animals↗
PubMed1998

Distribution of neurons innervating the uterus of the pig.

The distribution of neurons innervating the uterus of the pig was studied with the use of fluorescent retrograde tracer Fast Blue. Tracer injections were made into the uterine cervix, pericervical, middle and perioviductal part of the right uterine horn. After tracer injection into the uterine cervix tracer-positive neurons were found bilaterally in the inferior mesenteric ganglia, paracervical ganglia, paravertebral ganglia L1-S3 and dorsal root ganglia Th10-L4 and S2-S3. After tracer injection into the pericervical part of the right uterine horn the distribution of tracer-positive neurons resembled the one described earlier, except the tracer-positive neurons were absent in the left dorsal root ganglia. After tracer injection into the middle part of the right uterine horn tracer-positive neurons were found in the ipsilateral inferior mesenteric ganglion, bilaterally in the paracervical ganglia and in the ipsilateral paravertebral ganglia (L2-L6). Injection of the tracer into the perioviductal part of the right uterine horn revealed tracer-positive neurons bilaterally in the inferior mesenteric ganglia and paracervical ganglia and single cells in the ipsilateral paravertebral ganglia.

Amidines↗
PubMed1998

BCR/ABL-mediated leukemogenesis requires the activity of the small GTP-binding protein Rac.

The phenotype of hematopoietic cells transformed by the BCR/ABL oncoprotein of the Philadelphia chromosome is characterized by growth factor-independent proliferation, reduced susceptibility to apoptosis, and altered adhesion and motility. The mechanisms underlying this phenotype are not fully understood, but there is evidence that some of the properties of BCR/ABL-expressing cells are dependent on the activation of downstream effector molecules such as RAS, PI-3k, and bcl-2. We show here that the small GTP-binding protein Rac is activated by BCR/ABL in a tyrosine kinase-dependent manner. Upon transfection with a vector carrying the dominant-negative N17Rac, BCR/ABL-expressing myeloid precursor 32Dcl3 cells retained the resistance to growth factor deprivation-induced apoptosis but showed a decrease in proliferative potential in the absence of interleukin-3 (IL-3) and markedly reduced invasive properties. Moreover, compared with BCR/ABL-expressing cells, fewer BCR/ABL plus N17Rac double transfectants were capable of homing to bone marrow and spleen. Consistent with these findings, survival of SCID mice injected with the BCR/ABL plus N17Rac double transfectants was markedly prolonged as compared with that of mice injected with BCR/ABL-expressing cells. Together, these data support the important role of a Rac-dependent pathway(s) controlling motility in BCR/ABL-mediated leukemogenesis.

Animals↗
PubMed1998

The SH3 domain contributes to BCR/ABL-dependent leukemogenesis in vivo: role in adhesion, invasion, and homing.

To determine the possible role of the BCR/ABL oncoprotein SH3 domain in BCR/ABL-dependent leukemogenesis, we studied the biologic properties of a BCR/ABL SH3 deletion mutant (delta SH3 BCR/ABL) constitutively expressed in murine hematopoietic cells. delta SH3 BCR/ABL was able to activate known BCR/ABL-dependent downstream effector molecules such as RAS, PI-3kinase, MAPK, JNK, MYC, JUN, STATs, and BCL-2. Moreover, expression of delta SH3 BCR/ABL protected 32Dcl3 murine myeloid precursor cells from apoptosis, induced their growth factor-independent proliferation, and resulted in transformation of primary bone marrow cells in vitro. Unexpectedly, leukemic growth from cells expressing delta SH3 BCR/ABL was significantly retarded in SCID mice compared with that of cells expressing the wild-type protein. In vitro and in vivo studies to determine the adhesive and invasive properties of delta SH3 BCR/ABL-expressing cells showed their decreased interaction to collagen IV- and laminin-coated plates and their reduced capacity to invade the stroma and to seed the bone marrow and spleen. The decreased interaction with collagen type IV and laminin was consistent with a reduced expression of alpha 2 integrin by delta SH3 BCR/ABL-transfected 32Dcl3 cells. Moreover, as compared with wild-type BCR/ABL, which localizes primarily in the cytoskeletal/membrane fraction, delta SH3 BCR/ABL was more evenly distributed between the cytoskeleton/membrane and the cytosol compartments. Together, the data indicate that the SH3 domain of BCR/ABL is dispensable for in vitro transformation of hematopoietic cells but is essential for full leukemogenic potential in vivo.

Animals↗
PubMed1998

Make a difference: standardize your heel care practice.

The effective prevention and treatment of pressure ulcers has always been an essential nursing concern. Many advances, such as pressure reduction beds, have greatly reduced the incidence of ulcer development. In an urban teaching hospital the incidence of sacral ulcers decreased upon initiation of pressure reduction surfaces, while a concomitant increase in heel ulcers was noted. Heel ulcer prevention had not previously been singled out as a specific area of focus in skin pressure ulcer prevention. Given the increased incidence of occurrence of heel pressure ulcers in this institution's patient population, a multidisciplinary team met to address the issue of heel ulcer prevention. A quick, easy and user-friendly risk stratification tool was developed and guidelines for care of the at-risk patient were implemented. Initiation of the heel pressure ulcer identification tool and guidelines resulted in a decrease of heel pressure ulcer prevalence in the medical intensive care unit patient population.

Clinical Nursing Research↗
PubMed1997

Transformation of hematopoietic cells by BCR/ABL requires activation of a PI-3k/Akt-dependent pathway.

The BCR/ABL oncogenic tyrosine kinase activates phosphatidylinositol 3-kinase (PI-3k) by a mechanism that requires binding of BCR/ABL to p85, the regulatory subunit of PI-3k, and an intact BCR/ABL SH2 domain. SH2 domain BCR/ABL mutants deficient in PI-3k activation failed to stimulate Akt kinase, a recently identified PI-3k downstream effector with oncogenic potential, but did activate p21 RAS and p70 S6 kinase. The PI-3k/Akt pathway is essential for BCR/ABL leukemogenesis as indicated by experiments demonstrating that wortmannin, a PI-3k specific inhibitor at low concentrations, suppressed BCR/ABL-dependent colony formation of murine marrow cells, and that a kinase-deficient Akt mutant with dominant-negative activity inhibited BCR/ABL-dependent transformation of murine bone marrow cells in vitro and suppressed leukemia development in SCID mice. In complementation assays using mouse marrow progenitor cells, the ability of transformation-defective SH2 domain BCR/ABL mutants to induce growth factor-independent colony formation and leukemia in SCID mice was markedly enhanced by expression of constitutively active Akt. In retrovirally infected mouse marrow cells, the BCR/ABL mutant lacking the SH2 domain was unable to upregulate the expression of c-Myc and Bcl-2; in contrast, expression of a constitutively active Akt mutant induced Bcl-2 and c-Myc expression, and stimulated the transcription activation function of c-Myc. Together, these data demonstrate the requirement for the BCR/ABL SH2 domain in PI-3k activation and document the essential role of the PI-3k/Akt pathway in BCR/ABL leukemogenesis.

Animals↗
PubMed1997

Treatment of Philadelphia leukemia in severe combined immunodeficient mice by combination of cyclophosphamide and bcr/abl antisense oligodeoxynucleotides.

BACKGROUND: Philadelphia cells are human chronic myelogenous leukemia (CML) cells that contain the BCR/ABL oncogene (a fusion of the BCR and ABL genes). Selective eradication of these cells in vitro can be achieved by combined treatment with antisense phosphorothioate oligodeoxynucleotides ([S]ODNs) specifically targeted to this oncogene (bcr/abl [S]ODNs) and a suboptimal (for use as a single agent) dose of mafosfamide (the in vitro active form of cyclophosphamide). PURPOSE: We evaluated the ability of bcr/abl antisense [S]ODNs, alone or subsequent to treatment with a single injection of cyclophosphamide, to suppress the leukemic process induced in severe combined immunodeficient (SCID) mice by Philadelphia cells (i.e., primary CML-blast crisis [CML-BC] cells). In addition, we studied potential mechanisms that might explain the efficacy of the bcr/abl antisense [S]ODN-mafosfamide combination against Philadelphia cells in vitro. METHODS: The effects of treating leukemic mice with cyclophosphamide (25 mg/kg body weight; 25% of the dose required to eradicate evidence of leukemia in SCID mice) and/or bcr/abl antisense [S]ODNs were assessed by analysis of survival, by examination of bone marrow for the presence of leukemia cells (using a colony formation assay or using coupled reverse transcription and the polymerase chain reaction to screen for bcr/abl messenger RNA), and by examination of a variety of tissues for the presence of infiltrating leukemia cells. The induction of apoptosis (a cell death program) in vitro in primary CML-BC cells following treatment with bcr/abl antisense [S]ODNs plus or minus prior treatment with mafosfamide was monitored by use of a commercial assay. Relative cellular uptake of [S]ODNs by CML-BC cells treated in vitro with or without prior treatment with mafosfamide was determined by use of confocal microscopy and flow cytometry (for fluorescent [S]ODNs) or by use of blotting techniques that employed radioactively labeled probes (for extracted, unlabeled [S]ODNs). Levels of specific proteins in treated and untreated cells were determined by use of western blotting methods. Reported P values are two-sided. RESULTS: The disease process in leukemic mice was retarded substantially by combination treatment with cyclophosphamide and specific bcr/abl antisense [S]ODNs (P < .001, relative to treatment with specific antisense [S]ODNs alone, cyclophosphamide alone, or cyclophosphamide plus nonspecific [i.e., control] antisense [S]ODNs); 50% of the mice treated with cyclophosphamide and specific antisense [S]ODNs appeared to be cured of leukemia. The combination treatment was associated with increased induction of apoptosis. In addition, cellular uptake of bcr/abl antisense [S]ODNs appeared to be increased twofold to sixfold by prior treatment with mafosfamide. This increased uptake of [S]ODNs was associated with enhanced suppression of p210bcr/abl protein levels. CONCLUSIONS AND IMPLICATIONS: Combination therapy with antisense [S]ODNs targeted to specific oncogenes and less toxic doses of anticancer drugs may represent a rational strategy to purpose for the treatment of human leukemias.

Animals↗
PubMed1997

Immunohistochemical characteristics of nerve fibres supplying the porcine vas deferens. A colocalisation study.

Double-labelling immunofluorescence was used to investigate the coexistence of the catecholamine-synthesising enzymes, tyrosine hydroxylase and dopamine-beta-hydroxylase and several neuropeptides including neuropeptide Y, vasoactive intestinal polypeptide, Leu5-enkephalin, somatostatin, calcitonin gene-related peptide and substance P in nerve fibres supplying the vas deferens in juvenile and adult pigs. The study has revealed three major populations of nerve terminals innervating the organ: (1) noradrenergic fibres; (2) non-noradrenergic (putative cholinergic) fibres containing vasoactive intestinal polypeptide, neuropeptide Y and somatostatin, supplying almost exclusively the lamina propria; and (3) non-noradrenergic, presumably sensory fibres, containing calcitonin gene-related peptide and substance P. The population of noradrenergic nerves can be divided into three subpopulations: a somatostatin-containing, a Leu5-enkephalin-containing and a subpopulation immunonegative to the peptides investigated, in descending order of magnitude. Coexistence patterns of the substances existing within nerve fibres supplying the vas deferens blood vessels are clearly different from those found in nerve fibres innervating the organ wall. The majority of the noradrenergic fibres associated with blood vessels contain neuropeptide Y only, while non-noradrenergic perivascular nerves contain predominantly vasoactive intestinal polypeptide. The possibility of different sources of origin of the particular nerve fibre subpopulations supplying the porcine vas deferens and its blood vessels is discussed.

Animals↗
PubMed1997

Noradrenergic and peptidergic innervation of the testis and epididymis in the male pig.

This study was designed to investigate the distribution of noradrenaline (NE)- and peptide-containing nerves in the testis of the boar. Testes, as well as caput and cauda epididymides from five 5 week-old and 3 adult boars were sectioned and immunostained with antisera to tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (D beta H), neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), substance P (SP), calcitonin gene-related peptide (CGRP), Leu-enkephalin (L-ENK) and somatostatin (SOM). In addition, double-labelling immunofluorescence method was used to disclose the pattern of co-existence of these substances in the nerve fibres. The most abundant innervation was found in the cauda epididymidis, and the density of the nerves distinctly decreased towards the caput epididymidis. The testicular parenchyma and caput epididymidis was supplied with very scattered TH-, D beta H-, NPY-, VIP-, SP-, CGRP-, L-ENK- and SOM-containing nerve fibres. The present study has demonstrated for the first time the existence of CGRP, L-ENK and SOM in nerve fibres innervating the testis of a vertebrate species. Different subpopulations of nerve fibres, including TH+/D beta H+, D beta H+/NPY+, D beta H-/NPY+, D beta H+/NPY-, D beta H+/VIP+, D beta H-/VIP+, D beta H+/SP+, D beta H-/SP+, D beta H+/L-ENK+ D beta H-/L-ENK+, D beta H+/SOM+ and D beta H-/SOM+, were localized and documented.

Animals↗
PubMed1996

Increased expression of nitric oxide synthase in a subpopulation of rat sympathetic neurons after axotomy - correlation with vasoactive intestinal peptide.

Nitric oxide synthase (NOS) expression is increased in peripheral sensory and central motor neurons after axotomy. By applying double-labelling immunofluorescence and non-radioactive in situ hybridization, we have investigated the regulation of NOS in axotomized sympathetic rat superior cervical ganglia. Furthermore, co-localization of NOS with vasoactive intestinal peptide, which is also induced by axotomy, has been examined. Very few (<0.1%) NOS-expressing neurons are observed in control ganglia. Some large cell bodies located at the exit of the internal carotid nerve are additionally immunoreactive for vasoactive intestinal peptide. One week following postganglionic axotomy, the number of NOS-immunoreactive and NOS mRNA-expressing neurons increases but does not exceed 2% of the whole neuronal population. About 20% of these neurons are also immunoreactive for vasoactive intestinal peptide. Preganglionic nerve fibre meshworks that are immunoreactive for NOS in untreated ganglia disappear after ganglionic decentralization, whereas some presumably postganglionic fibres remain visible after combined axotomy and decentralization. The findings are indicative of an increased synthesis of NOS in a small subset of postganglionic neurons of the rat superior cervical ganglion, possibly because of the loss of target-derived factors that inhibit nitric oxide synthesis under normal conditions.

Adrenergic Fibers↗