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  • Intraductal delivery of adenoviruses targets pancreatic tumors in transgenic Ela-myc mice and orthotopic xenografts. 23328228

    Gene-based anticancer therapies delivered by adenoviruses are limited by the poor viral distribution into the tumor. In the current work we have explored the feasibility of targeting pancreatic tumors through a loco-regional route. We have taken advantage of the ductal network in the pancreas to retrogradelly inject adenoviruses through the common bile duct in two different mouse models of pancreatic carcinogenesis: The transgenic Ela-myc mice that develop mixed neoplasms displaying both acinar-like and duct-like neoplastic cells affecting the whole pancreas; and mice bearing PANC-1 and BxPC-3 orthotopic xenografts that constitute a model of localized human neoplastic tumors. We studied tumor targeting and the anticancer effects of newly thymidine kinase-engineered adenoviruses both in vitro and in vivo, and conducted comparative studies between intraductal or intravenous administration. Our data indicate that the intraductal delivery of adenovirus efficiently targets pancreatic tumors in the two mouse models. The in vivo application of AduPARTKT plus ganciclovir (GCV) treatment induced tumor regression in Ela-myc mice. Moreover, the intraductal injection of ICOVIR15-TKT oncolytic adenoviruses significantly improved mean survival of mice bearing PANC-1 and BxPC-3 pancreatic xenografts from 30 to 52 days and from 20 to 68 days respectively (p less than 0.0001) when combined with GCV. Of notice, both AduPARTKT and ICOVIR15-TKT antitumoral responses were stronger by ductal viral application than intravenously, in line with the 38-fold increase in pancreas transduction observed upon ductal administration. In summary our data show that cytotoxic adenoviruses retrogradelly injected to the pancreas can be a feasible approach to treat localized pancreatic tumors.
    Tipo de documento:
    Referencia
    Referencia del producto:
    MAB3068

  • Distribution and severity of spontaneous lesions in the neuroepithelium and Bowman's glands in mouse olfactory mucosa: age-related progression. 19142664

    Age-related changes were examined in the distribution and severity of spontaneous lesions in the neuroepithelium and Bowman's glands in mouse olfactory mucosa. The olfactory mucosa of female ICR mice at postnatal ages from 10 days to 16 months were investigated histologically by hematoxylin and eosin staining, high-iron diamine-Alcian blue (HID-AB) staining, and immunohistochemistry for olfactory marker protein (OMP), betaIII tubulin (betaIIIT), and Ki67. The lesions in the neuroepithelium and Bowman's glands were quantitatively assessed by morphometric analyses of sections stained with anti-OMP antibody or HID-AB. The first appearance of neuroepithelial abnormality was observed in the dorsomedial portion of the olfactory mucosa in 5-month-old mice. The distribution and severity of lesions progressed with increasing age. In mildly affected epithelium in which OMP-positive olfactory receptor neurons (ORNs) were present but in smaller amounts, the numbers of betaIIIT-positive and Ki67-positive neuroepithelial cells tended to be increased, indicating that neurogenesis was upregulated in these areas. In contrast, severely affected epithelium in which OMP-positive ORNs were virtually absent showed high variability in the numbers of betaIIIT- and Ki67-positive cells among the areas examined, probably reflecting differences in the capacity of the basal cells remaining in the affected area to generate new neuronal cells. Histological analysis with HID-AB revealed that spontaneous lesions in Bowman's glands also occurred in aged mouse olfactory mucosa. Lesions in the neuroepithelium and underlying Bowman's glands tended to be spatially co-localized, suggesting a close association between pathogeneses in these two structures. Moreover, lesions in Bowman's glands were associated with changes in the biochemical composition of mucus on the olfactory mucosa. This information should prove useful in improving the understanding of the pathogenetic mechanisms underlying age-related changes in the peripheral olfactory system.
    Tipo de documento:
    Referencia
    Referencia del producto:
    AB1554
    Nombre del producto:
    Anti-Nerve Growth Factor Receptor Antibody, p75

  • The expression of renin-angiotensin system components in the human gastric mucosa. 20739374

    The aim of the present study was to map the distribution of representative protein components of the renin-angiotensin system (RAS) in the human gastric mucosa.Biopsies from the antral and corporal mucosa of healthy Helicobacter pylori negative and positive volunteers were assessed by histology, Western blot and immunohistochemistry for angiotensin II subtype 1 and 2 receptors (AT1R, AT2R) and other RAS components (angiotensinogen, renin, angiotensin converting enzyme, and neprilysin). Mucosal levels of myeloperoxidase (MPO) served as a protein marker of neutrophil infiltration.AT1R and AT2R were located in a variety of cells in the human gastric mucosa, including AT1R on a subpopulation of endocrine cells in the antral mucosa. Angiotensinogen and renin were expressed by resident mesenchymal cells in lamina propria. All investigated RAS components were found in vascular endothelial cells. The AT1R protein expression was 3-4 times higher in the gastric mucosa of H. pylori positive subjects compared to the gastric mucosa of H. pylori negative subjects (p less than 0.05). Gastric mucosal AT1R protein expression correlated positively with neutrophil infiltration (r = 0.7, p less than 0.05).Protein components of RAS are present in the human gastric mucosa. The results suggest an angiotensin II mediated impact on mucosal epithelial functions, antral endocrine properties, microvascular permeability, and gastric inflammation.
    Tipo de documento:
    Referencia
    Referencia del producto:
    Múltiplo
    Nombre del producto:
    Múltiplo

  • The distribution of p75 neurotrophin receptor-immunoreactive cells in the forebrain of the common marmoset (Callithrix jacchus). 9222533

    The distribution of neurones that could be stained immunohistochemically with antibody to the p75 neurotrophin protein was studied in the forebrain of the common marmoset. The p75-immunoreactive forebrain cells appear to correspond to choline acetyltransferase-immunoreactive (i.e., cholinergic) neurones. Two populations of cells could be distinguished on the basis of the intensity of p75 immunostaining. Moderately stained cells correspond to cholinergic interneurones of the caudate and putamen, while intensely stained cells correspond to the cholinergic neurones projecting to the cortex, amygdala, and hippocampus, located in the septum, diagonal band, and basal nucleus of Meynert. The distribution of cells of the diagonal band/basal nucleus complex is more extensive in the marmoset than in other primate species, extending into parts of the postcommissural fornix via the posterior septum, and by small projections dorsal to the anterior commissure and via the thalamic fasciculus from the basal nucleus; the posterior extent of the basal nucleus continues extensively into the lamina between the globus pallidus and the putamen.
    Tipo de documento:
    Referencia
    Referencia del producto:
    AB143
    Nombre del producto:
    Anti-Choline Acetyltransferase (ChAT) Antibody

  • Wide distribution of laminin-5 gamma 2 chain in basement membranes of various human tissues. 9721586

    Laminin 5 (LN5), a heterotrimer of laminin alpha 3. beta 3. and gamma 2 chains. is a laminin isoform which strongly promotes adhesion. migration. and scattering of cells through binding to integrins alpha 3 beta 1, alpha 6 beta 1 and alpha 6 beta 4. To get an insight into the physiological functions of LN5, we prepared a mouse monoclonal antibody to human laminin gamma 2 chain and used it for immunohistochemical analysis of laminin gamma 2 chain in normal human tissues. The basement membranes of various epithelial tissues, such as the skin, lung, small intestine, stomach, kidney and prostate, were immunostained with the anti-laminin gamma 2 chain monoclonal antibody. In addition, the basement membrane of the surface germinal epithelium in the ovary was also positive for laminin gamma 2 chain. These results suggest general roles of LN5 in the anchorage of various types of epithelial cells to the underlying basement membrane and in the expression of their cellular functions. Moreover, deposition of laminin gamma 2 chain around small arteries and veins was observed in the thymus and spleen. This lymphatic organ-specific expression of vascular LN5 might provide a novel function of LN5 in immune responses.
    Tipo de documento:
    Referencia
    Referencia del producto:
    MAB19562
    Nombre del producto:
    Anti-Laminin-5 (γ2 chain) Antibody, clone D4B5

  • Roles of transforming growth factor-alpha and epidermal growth factor in chick limb development. 9758702

    We have examined the distribution of transforming growth factor-alpha (TGF-alpha), epidermal growth factor (EGF), and the chicken EGF receptor (c-erbB), in embryonic chick limbs. Prior to limb budding, TGF-alpha is present in prospective limb-forming mesoderm and in prospective apical ectodermal ridge (AER)-forming ectoderm, but is not detected in non-limb-forming flank mesoderm or ectoderm, nor in presumptive non-AER-forming limb ectoderm, suggesting possible roles in initial limb formation and AER induction. Consistent with this possibility, TGF-alpha is present in the mesoderm of the wing buds of the amelic chick mutants limbless and wingless, which form and bud normally, but is absent from limbless and wingless ectoderm, which fails to form an AER. TGF-alpha and EGF are present in the AER of the developing limb, and TGF-alpha, EGF, and c-erbB are present in the underlying subridge mesoderm, suggesting possible roles in reciprocal AER/subridge mesoderm interactions required for limb outgrowth. We found that exogenous TGF-alpha and EGF can promote the outgrowth of limb mesoderm in the absence of the AER in vitro and can also promote the outgrowth of limbless and wingless wing bud explants. EGF is present in ventral but not dorsal limb ectoderm, suggesting a role for EGF in specification of ventral ectoderm. TGF-alpha and EGF are not detected in the differentiating cartilaginous elements or muscle primordia of the limb, suggesting that cessation of TGF-alpha and EGF expression may be required for cartilage and muscle formation. We have found that exogenous TGF-alpha and EGF inhibit chondrogenesis and myogenesis of limb mesenchyme in vitro. Together these results indicate that signaling through the EGF receptor via endogenous TGF-alpha and EGF may be important for initial limb formation, AER induction, outgrowth of limb mesoderm, and regulation of limb chondrogenic and myogenic differentiation.
    Tipo de documento:
    Referencia
    Referencia del producto:
    06-102
    Nombre del producto:
    Anti-EGF Antibody, neutralizing

  • Synaptic distribution of the NR1, NR2A and NR2B subunits of the N-methyl-d-aspartate receptor in the rat lumbar spinal cord revealed with an antigen-unmasking technique. 15610162

    Glutamate is the main excitatory neurotransmitter in the spinal cord and acts on several types of receptor, including N-methyl-d-aspartate (NMDA) receptors, which play an important role in synaptic plasticity and chronic pain. Three families of NMDA receptor subunit have been identified: NR1, NR2 (A-D) and NR3 (A and B). NMDA receptors are heteromeric channels that contain NR1 with at least one NR2 subunit. There is extensive evidence that NMDA receptors are present in spinal cord but little is known about their synaptic distribution. We have used an antigen-unmasking method involving pepsin treatment to reveal NR1, NR2A and NR2B subunits and have compared their distribution with that of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor GluR2 subunit, which is thought to be present at most glutamatergic synapses throughout the spinal cord. After pepsin treatment, punctate labelling was seen with antibodies against each of these subunits. Although NR1 puncta were present throughout the grey matter, NR2A was concentrated in laminae III-IV and NR2B in laminae I-II. The majority of puncta labelled with each NMDA receptor antibody were GluR2-immunoreactive, which suggests that they were present at synapses, and this was confirmed with electron microscopy for the NR1 and NR2A antibodies. However, many GluR2-immunoreactive puncta did not show NMDA receptor immunoreactivity. In laminae I-II, most NR2B puncta were also NR1-immunoreactive and a similar arrangement was found for NR2A/NR1 in laminae III-IV. These results suggest that many, but not all, glutamatergic synapses in the spinal cord possess NMDA receptors and that subunit composition varies in different regions.
    Tipo de documento:
    Referencia
    Referencia del producto:
    MAB397
    Nombre del producto:
    Anti-Glutamate Receptor 2 Antibody, extracellular, clone 6C4

  • The Structural Relationship between the Microvasculature, Neurons, and Glia in the Human Retina. 19643967

    Purpose. To develop a new technique for detailed study of the spatial distribution of retinal and choroidal microvasculature and their relationship to neurons and glial cells at the cellular level in human cadaveric eyes. Methods. Twenty-six human donor eyes were used. Wherever possible, the central retinal artery and a branch of the posterior ciliary artery were individually cannulated and perfused with oxygenated Ringer's solution with 0.5% bovine serum albumin. The perfusion pressure was continuously monitored. Once residual blood was washed out, the perfusate solutions were switched to fixative, membrane-permeabilizing solution and selected labeling solutions. The eyes were then immersion fixed and the retina and choroid flat-mounted for immunolabeling and confocal imaging before cryosectioning. The microstructures of vascular, glial, and neuronal cells in the retina and the stroma in the choroid were studied. Results. The retinal microvasculature was fully perfused and stained by cannulation of the central retinal artery. Regional distribution of choroidal vasculature perfusion was dependent on the specific feeder artery cannulated. The detailed spatial relationship between endothelial cells, glial cells, and neurons at the cellular and subcellular levels was identified with confocal microscopy and immunohistochemical labeling of retinal sections. In the choroid, endothelial cells were clearly identifiable down to the level of the intracellular cytoarchitecture of the choriocapillaris, along with their relationship to Bruch's membrane and the feeding and drainage vessels. Conclusions. A microperfusion fixation and staining technique has been developed that allows studies of the structural relationships of vascular, glial, and neuronal elements at the cellular level in human donor eyes.
    Tipo de documento:
    Referencia
    Referencia del producto:
    Múltiplo
    Nombre del producto:
    Múltiplo

  • Immunohistochemical study on the distribution of alpha and beta subunits of S-100 protein in human neoplasm and normal tissues. 6145248

    The immunohistochemical distribution and localization of the alpha and beta subunits of S-100 protein in human neoplasms and normal tissues were studied by the PAP method using monospecific rabbit antibodies against each subunit. Beta subunit immunoreactivity was detected in all S-100-positive cells and tumors reported previously. In contrast alpha subunit immunoreactivity was absent from Schwann cells, schwannomas, neurofibromas, granular cell myoblastomas, pituicytes of the neurohypophysis, Langerhans cells, interdigitating reticulum cells, and histiocytosis X cells. Interestingly, only the alpha subunit was detected in neurons of both central and peripheral nervous system, and in lymph node macrophages. Human S-100-positive cells are divided into three groups; the first is composed of cells containing only the beta subunit (probably S-100b; beta beta), the second consists of cells containing both the alpha and beta subunits, and the third is composed of cells containing only the alpha subunit (probably S- 100ao ; alpha alpha). The ontogentic relationships between S-100-positive cells and tumors are discussed in the light of these findings.
    Tipo de documento:
    Referencia
    Referencia del producto:
    AB941