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Biomedical subjects

A Weller

Publications and source records attributed to A Weller.

At least 19 recordsLinked to original sources
PubMed1992

Cloning of the mouse endothelial selectins. Expression of both E- and P-selectin is inducible by tumor necrosis factor alpha.

E-selectin (ELAM-1) and P-selectin (GMP-140, PADGEM, CD62) have both been described as human endothelial cell adhesion molecules for neutrophils and monocytes. Cell surface appearance of these two proteins on human umbilical vein endothelial cells can be regulated by different mechanisms: E-selectin is transcriptionally induced, within hours, by tumor necrosis factor alpha (TNF-alpha) while P-selectin is transported from storage granules to the plasma membrane within minutes upon induction by various stimulating agents. We have obtained cDNA clones covering the full-length coding sequence of the homologous mouse proteins for both endothelial selectins. We show that synthesis of mouse P-selectin, like that of E-selectin, is transiently induced by TNF-alpha in several endothelioma cell lines derived from different mouse tissues. This induction was monitored on both the RNA as well as the protein level. The TNF induced, newly synthesized P-selectin protein was detected on the cell surface. Protein expression of P-selectin increased with a slightly lower rate than expression of E-selectin. In organ cultures of lung tissue from TNF-injected mice, the synthesis of P-selectin was clearly elevated compared to control mice. The bovine P-selectin homolog recognized by cross-reaction with anti-mouse P-selectin antibodies was also TNF-inducible in primary capillary endothelial cells from adrenal cortex and in aorta-derived endothelial cells. Thus, P-selectin can be regulated on two different levels. While the transport of stored P-selectin to the cell surface is controlled by regulated secretion of storage granules, the synthesis and surface expression can be induced by TNF-alpha similarly to that of E-selectin.

Amino Acid Sequence↗
PubMed1992

Plastic surgery on children with Down syndrome: parents' perceptions of physical, personal, and social functioning.

Plastic facial surgery is being carried out on children with Down syndrome with the objective of improving these children's physical, personal, and social functioning. This study investigated the effect of such surgery on parents' perceptions, both of the current status of their children's functioning and of changes in this functioning. Perceptions of parents of children who had undergone this surgery in Israel in the years 1982 and 1983 were compared with perceptions of parents of children who had not undergone the operation. This comparison produced little evidence for the positive impact of the surgery on parents' perceptions of their children's physical, personal, and social functioning.

Activities of Daily Living↗
PubMed1992

Expression of tenascin in the developing and adult cerebellar cortex.

Since tenascin may influence neuronal cell development, we studied its expression pattern using immunocytochemistry, in situ hybridization, Northern blot analysis, and immunochemistry in the developing and adult mouse cerebellar cortex. Tenascin immunoreactivity was detectable in all layers of the developing cerebellar cortex. In the external granular layer, only the radially oriented processes of Golgi epithelial cells were immunoreactive, whereas the densely packed cell bodies were immunonegative. Tenascin was hardly detectable at contact sites between migrating granule cells and processes of Golgi epithelial cells. Axons of granule cells in the molecular layer were immunoreactive, whereas their cell bodies in the internal granular layer lacked detectable levels of tenascin. By in situ hybridization, only Golgi epithelial cells and astrocytes of the internal granular layer and prospective white matter, but not nerve cells, could be shown to synthesize detectable levels of tenascin mRNA in the developing mouse cerebellar cortex. Thus, tenascin in the cerebellar cortex seems to be a glia-derived molecule that becomes adsorbed to neuronal surfaces in a topographically restricted pattern in situ. Levels of tenascin protein and mRNA decreased significantly with increasing age. In the adult, tenascin immunoreactivity was weak and mainly restricted to the molecular layer and tenascin mRNA was confined to Golgi epithelial cells, indicative for a functional heterogeneity in differentiated cerebellar astrocytes. Quantitative immunoblot analysis revealed that the 225 and 240 kDa components of tenascin were developmentally downregulated at a faster rate than the 190 and 200 kDa components, corresponding to the faster downregulation of the 8 kilobase (kb) mRNA species compared to the 6 kb mRNA species as revealed by Northern blot analysis. These observations indicate a differentially regulated expression of the tenascin components. We hypothesize that glia-derived tenascin modifies the functional properties of nerve cell surfaces and that tenascin is involved in such different morphogenetic events as neurite growth and oligodendrocyte distribution.

Animals↗
PubMed1992

Expression of tenascin by vascular smooth muscle cells. Alterations in hypertensive rats and stimulation by angiotensin II.

The extracellular matrix glycoprotein tenascin is associated with remodeling events in many embryonic and pathologic tissues. The expression of tenascin has been investigated by immunohistochemistry in blood vessels of Wistar-Kyoto (normotensive) and spontaneously hypertensive rats. Weak tenascin staining was present throughout the tunica media of large and small arteries from normotensive animals; strong staining was only detectable at branching sites. In arteries from hypertensive animals, foci of strong tenascin staining were scattered throughout the tunica media. The expression of tenascin mRNA and protein by rat aortic smooth muscle cells cultured in serum-free medium was induced by the vasoconstrictor peptide angiotensin II. Transforming growth factor-beta and platelet-derived growth factor also stimulated tenascin mRNA expression. Vascular smooth muscle cells attached specifically to a substratum of tenascin, but remained rounded. Thus, increased focal tenascin expression by vascular smooth muscle cells is associated with hypertension, and may mediate angiotensin II-induced changes in vascular structure in hypertension.

Angiotensin II↗
PubMed1991

Molecular cloning of gp 80, a glycoprotein complex secreted by kidney cells in vitro and in vivo. A link to the reproductive system and to the complement cascade.

cDNA clones coding for the gp 80 heterodimeric glycoprotein complex secreted constitutively at the apical surface of Madin-Darby canine kidney (MDCK) cells have been isolated from MDCK cDNA libraries in lambda gt11 and lambda gt10. The cloned sequences encode a polypeptide chain of 445 amino acids. The deduced amino acid sequence of the gp 80 protein reveals 80% homology to rat SGP-2, a major secretory protein of the testes epithelium and 83% homology to SP-40,40, a human complement-associated protein. SGP-2 and SP-40,40 have been proposed to be serum and seminal forms of the same protein. The sequence homology as well as the results of Southern and Northern blot analyses and immunological studies suggest that gp 80 is the canine homolog of the rat SGP-2 and the human SP-40,40. The protein is expressed in the embryonic kidney already early during organogenesis. In the adult kidney the protein has been localized along the luminal surfaces of the proximal and distal tubule and the collecting duct cells.

Amino Acid Sequence↗
PubMed1991

Development and growth of mouse embryonic kidney in organ culture and modulation of development by soluble growth factor.

Differentiation of the metanephrogenic mesenchyme is triggered by an inductive tissue interaction between an inducer tissue and the mesenchyme. It is generally believed that the epithelial ureter bud acts as an inducer during in vivo development. In response to the inductive stimulus most of the mesenchymal cells convert into epithelial cells, while a small fraction differentiates into stromal cells. In vitro, differentiation of isolated mesenchyme to epithelium can be induced by a variety of embryonic tissues, but nothing is known about the molecular nature of the inducing stimulus. In recent years, large numbers of polypeptide growth factors have been described, which in addition to proliferative effects were shown to exert effects on a variety of biological phenomena such as chemotaxis, inflammation, tissue repair, or induction of embryonic development. We therefore analyzed whether growth factors in the absence of inducer tissue can induce isolated kidney mesenchyme to differentiate into epithelium or interstitium. As expected, both growth and differentiation into epithelium were stimulated by an inducer tissue, the spinal cord. We found that none of the various growth factors tested (including epidermal growth factor, transforming growth factors alpha and beta, insulin-like growth factors I and II, fibroblast growth factor, platelet-derived growth factor, and retinoic acid) could mimick the effect of an inducer tissue, although we tested the factors over a wide concentration range. One of the tested factors, epidermal growth factor (EGF) stimulated the mesenchymal cells to become stromal cells, although it could not stimulate development into epithelium. EGF could stimulate stromal development both when the mesenchyme was cultured in isolation and when the mesenchyme was stimulated by an inducer tissue to become epithelium. The expansion of the stromal compartment in response to EGF treatment occurred at the expense of the epithelial cells, but EGF could not completely suppress the formation of epithelium. These data suggest the presence of EGF receptors in the developing kidney, but since application of soluble EGF leads to abnormal development, soluble EGF cannot be the natural ligand. We suggest that locally produced mitogens with an EGF-like structure may regulate the relative amounts of stroma (interstitium) and epithelium in the developing kidney.

Animals↗
PubMed1991

Amino acid sequence of mouse tenascin and differential expression of two tenascin isoforms during embryogenesis.

We have isolated cDNA clones for mouse tenascin and analyzed expression of tenascin mRNAs during embryonic development of the kidney and gut. The deduced amino acid sequence of the mouse tenascin cDNAs shows a modular structure of repeats similar to chicken and human tenascin. In mouse there are 14.5 cysteine-rich repeats with similarity to the EGF repeat, followed by several repeats with similarity to the type III repeat of fibronectin. A longer variant contains 13 fibronectin type III repeats, whereas a shorter splice variant of mouse tenascin lacks the 5 type III repeats that occur directly after the fifth repeat in the longer variant. Contrary to the chicken and human sequences, mouse tenascin does not contain an RGD sequence in the third type III repeat implicated in cell attachment, or in any other positions. In Northern hybridizations to RNA from primary embryonic fibroblasts, the cDNA clone M 20/1 detects two mRNAs with sizes close to 6 and 8 kb. This, and the other data presented here suggest that the two major mouse tenascin polypeptides arise through an alternative RNA splicing. The two major mRNAs are differentially expressed during development. The 8-kb mRNA is more prominent than the 6-kb mRNA throughout prenatal kidney development, but during postnatal development the ratio of the two mRNAs changes. A different expression pattern is seen in the developing gut where the 6-kb mRNA predominates during embryogenesis with the 8-kb mRNA appearing later. The mRNA data of the developing gut correspond with previous protein data, which showed that the shorter Mr 210,000 polypeptide predominates during earlier developmental stages and the larger Mr 260,000 polypeptide appears later in the embryonic gut (Aufderheide, E., and P. Ekblom. 1988. J. Cell Biol. 107:2341-2349).

Amino Acid Sequence↗
PubMed1991

Naturally occurring anti-idiotypic antibodies--mechanisms for autoimmunity and immunoregulation?

Coxsackievirus B3 (CVB3) infections induce myocardial inflammation which is presumably mediated by autoimmune mechanisms in the experimental murine model. Naturally occurring antibodies that also bind to myocytes have been identified that can either abrogate or enhance cardiac injury by modulating the immune response. Monoclonal antibodies derived from CVB3-infected mice were immobilized to plastic and overlaid with spleen cells obtained from mice infected with 5 x 10(4) plaque forming units of CVB3 0 to 8 days earlier. Controls consisted of either myocytes or virus adsorption monolayers. After incubation, non-adherent lymphocytes were removed, the adherent cells were recovered and cultured on either virus or myocytes for 48 h at 37 degrees C. The lymphocytes were removed and any antibody binding to the virus or myocytes was detected using goat anti-mouse IgG and IgM in a urease enzyme-linked immunoadsorption assay (ELISA). The original unfractionated spleen cell population added directly to the ELISA wells showed reactivity to both virus and myocytes. Cells adsorbed to myocytes made primarily myocyte-reactive antibody and cells adsorbed to virus made primarily virus-reactive antibody. Cells adsorbed to the heart-reactive mAB (10A1) made primarily virus-specific antibody suggesting this autoantibody might be an anti-idiotype of the virus-reactive response.

Animals↗
PubMed1990

Endogenous cholecystokinin reduces feeding in young rats.

The hypothesis that endogenous cholecystokinin (CCK) released from the small intestine during feeding causes satiety was tested in rat pups, 9 to 12 days old. Intragastric administration of soybean trypsin inhibitor, a procedure that releases CCK from the small intestine, decreased the subsequent intake of a test meal. This effect was reversed by prior treatment with MK-329, a selective antagonist of CCK at alimentary-type CCK (CCK-A) receptors. Thus, endogenous, small intestinal CCK can cause satiety in the neonatal rat and this effect involves CCK-A receptors.

Animals↗
PubMed1990

Cholecystokinin conditioning in rats: ontogenetic determinants.

Low doses (0.12-2.0 micrograms/kg) of cholecystokinin octapeptide (CCK), administered intraperitoneally, support the formation of conditioned odor preference in neonatal and weanling rats. Exposure to a novel odor was paired with CCK injection, and the rats' olfactory choices were assessed 24 hr later. Rats at 5, 11, and 22 days of age preferred the odor previously associated with CCK, compared with vehicle-injected littermates. In contrast, CCK failed to support olfactory conditioning in 28-day-old rats, whether they were (a) weaned and independently housed, (b) residing with the dam and suckling, or (c) fed only milk. Adult rats also did not establish an odor preference with CCK as the unconditioned stimulus. Thus, CCK's changing impact from positive to neutral probably occurs during the rats' 4th postnatal week and may be related to maturational changes occurring during the final stages of weaning.

Animals↗
PubMed1990

Separation of opioid from nonopioid mediation of affect in neonatal rats: nonopioid mechanisms mediate maternal contact influences.

A causal distinction is established in infant Norway rats between opioid- and nonopioid-mediated determinants of behavior. Contact influences are shown to be mediated by nonopioid pathways, whereas gustatory influences are shown to be opioid mediated. Specifically, naltrexone (0.5 and 1.0 mg/kg) did not at all diminish quieting exerted by contact with an anesthetized dam but completely reversed the quieting effects of morphine in isolated rats. Naloxone (5 mg/kg) did not affect the latencies with which nondeprived or 8-hr deprived rats 9, 12, 15, and 18 days of age attached to the nipples of anesthetized dams, nor did naloxone (5 and 10 mg/kg) cause any systematic change in nipple attachment in 10- and 18-day-old rats that had been deprived of their dam for either 0, 8, or 24 hr. In a 3rd experiment, naloxone (5 mg/kg) did not significantly reduce milk intake by 9-, 12-, 15-, or 18-day-old rats from the nipple when milk letdown was induced by oxytocin. Moreover, naloxone (5 and 10 mg/kg) did not reduce milk intake in Day-10 rats that, while suckling, received milk via a cannula placed in the posterior portion of the tongue at the level of the intermolar eminence or in rats that obtained milk directly from their awake mother. In contrast, milk intake was significantly reduced by naltrexone (0.25-1.0 mg/kg) in Day-10 rats that obtained milk (a) by licking it off a saturated substrate or (b) through an indwelling cannula located in the anterior portion of the lower jaw. (Milk delivered at this placement is thought to engage feeding systems by its taste and texture.) In a final set of experiments in Day-10 rats, intake of milk delivered via anterior jaw cannulae was reduced by naloxone (5 and 10 mg/kg) in rats that were either isolated, in contact with an anesthetized dam, or attached to her nipples. On the basis of resistance to naloxone and naltrexone administration, these experiments demonstrate that behavioral influences of the tactile (and possibly olfactory) qualities of the mother are not mediated by opioid systems. Implications for understanding the means through which mothers can influence their young and the infantile mediators of these maternal influences are discussed.

Affect↗
PubMed1989

Stress-reducing effects of ingesting milk, sugars, and fats. A developmental perspective.

A developmental approach to the study of feeding is proposed that considers social complexity and its biological mediation as core determinants of later ingestive patterns. Evidence is presented for opioid-mediated influences of milk and its major constituents and for nonopioid-mediated channels for contact comfort. Consideration of these factors might help us better understand some of the determinants of human feeding disorders such as bulimia and anorexia nervosa.

Animals↗
PubMed1989

Clinical and experimental aspects of viral myocarditis.

Picornaviruses are frequently implicated as the etiological agents of acute myocarditis. This association is based historically on serological evidence of rising antibody titers to specific pathogens and more recently on identification of viral genomic material in endocardial biopsy specimens through in situ hybridization. Only rarely is infectious virus isolated from either the patient or the heart during periods of maximum myocardial inflammation and injury. Thus, despite a probable viral etiology, much interest centers on the role of the immune system in cardiac damage and the likelihood that the infection triggers an autoimmune response to heart-specific antigens. Heart-reactive antibodies and T cells are found in most myocarditis patients, and immunosuppressive therapy has proven beneficial in many, though not all, cases. Furthermore, murine models of coxsackievirus group B type 3-induced myocarditis also demonstrate that virus infection initiates autoimmunity and that these autoimmune effectors are predominately responsible for tissue injury. How virus-host interactions overcome presumed self-tolerance to heart antigens is discussed, and evidence supporting various theories of virus-initiated autoimmunity and disease pathogenesis are delineated.

Animals↗
PubMed1989

[Nursery schools, a site for exposure to house dust mite allergens?].

In June 1988, 110 dust samples from carpets, cushions, mattresses and upholstered furniture were collected by vacuum cleaner in 33 municipal nursery schools. All samples were assessed with guanine test strips (Acarex). In all samples giving moderately or strongly positive results in these tests (guanine stages 2 and 3) and in 10 random samples each from of stages 1 (weakly positive) and 0 (negative), mites were counted by light microscope. In 36% of the nursery schools, objects with guanine stages 2 or 3 were found, which indicates a high allergen burden. The high guanine stages were found only in mattresses, cushions and upholstered furniture. Nursery schools can be source areas of significant allergen exposure relevant for children with dust mite allergies.

Allergens↗
PubMed1988

Acute and repeated gestational stress affect offspring learning and activity in rats.

This study assessed possible long-lasting effects of mild, indirect prenatal stress upon offspring. Dams were restrained for 30 minutes either once or four times during the third trimester of gestation. Their male offspring were challenged in adulthood with a series of appetitive operant learning tasks. Both acute and repeated prenatal maternal restraint retarded the performance of the offspring in a selective manner: deficits appeared during the reversal stage of an operant discrimination task, with no effect on acquisition, discrimination or extinction. Repeated, but not acute, maternal stress was also associated with offspring hyperactivity. This highlights the differential impact of varying the stress schedule. Furthermore, use of multiple measures of learning uncovered a long-lasting, selective effect of relatively mild, indirect prenatal manipulation.

Animals↗
PubMed1988

Behavioral evidence for cholecystokinin-opiate interactions in neonatal rats.

In adult mammals, cholecystokinin (CCK)-opiate interactions are complex and task dependent. Specifically, CCK antagonizes opiate effects in some cases, yet acts similarly to opiate agonists in others. The present study used behavioral measures to determine how CCK interacts with opiates in neonatal rats. CCK, at doses of 1 microgram/kg and higher, markedly reduced isolation-induced distress vocalization in rat pups. Moreover, CCK selectively prevented naltrexone antagonism of opiate-mediated reduction in distress vocalization in 3- and 11-day-old rats. Yet CCK did not affect opiate-induced analgesia, as measured by the hot-plate paw-lift response. Thus CCK either did not interact with opiates or did so agonistically, with the same (low) dose range, and within subjects. These findings suggest independence of stress and pain systems in neonatal rats and demonstrate a functional interaction between CCK and opioid systems.

Animals↗