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At least 883 records · Page 49Linked to original sources
PubMed1990

Experimental yolk sac dysfunction as a model for studying nutritional disturbances in the embryo during early organogenesis.

Our investigations concerning the importance of cell surface macromolecules during embryonic development led us to the discovery in 1961 that heterologous anti-rat kidney serum produced teratogenesis, growth retardation and embryonic death when injected into the pregnant rat during early organogenesis. It was established that IgG was the teratogenic agent, primarily directed against the visceral yolk sac (VYS) but not the embryo. Heterologous anti-rat VYS serum was prepared which was teratogenic localized in the VYS and served as a model for producing VYS dysfunction and embryonic malnutrition. The role of the yolk sac placenta in histiotrophic nutrition is now recognized to be critical for normal embryonic development during early organogenesis in the rodent. VYS antiserum affects embryonic development primarily by inhibiting endocytosis of proteins by the VYS endoderm, resulting in a reduction in the amino acids supplied to the embryo. Our laboratory has recently developed teratogenic monoclonal yolk sac antibodies (MCA) which can be utilized; to study VYS plasma membrane synthesis and recycling, to compare yolk sac function among different species, and to identify components of the plasma membrane involved in pinocytosis. MCA prepared against certain VYS antigens provide an opportunity to study embryonic nutrition with minimal interference with the nutritional state of the mother. Recent developments in the study of the human yolk sac along with our laboratory's ability to isolate a spectrum of yolk sac antigens, prepare monoclonal antibodies, and perform functional studies, should provide information that will increase our understanding of yolk sac function and dysfunction in the human and determine the relative importance of various amino acids to normal development during mammalian organogenesis.

Animals↗
PubMed1991

Ultrastructure and function of the rat yolk sac: damage caused by teratogenic anti-VYS serum and recovery.

It was hypothesized that heterologous anti-rat visceral yolk sac serum (AVYS) exerts its teratogenic effect by reducing the endocytosis of serum proteins by the visceral yolk sac (VYS), thus reducing the supply of amino acids to the embryo and VYS. To evaluate this hypothesis, we studied the effect of teratogenic AVYS on the endocytic function of the VYS and the ultrastructure of the VYS and parietal yolk sac (PYS). Rat conceptuses were exposed to a teratogenic dose of AVYS on the 10th day of gestation in vivo or in vitro. Control and AVYS-exposed specimens were collected 24-192 hr later and prepared for scanning and transmission electron microscopy (SEM and TEM, respectively) utilizing standard procedures. The Endocytic Index was calculated for the VYS utilizing standard procedures. Approximately 97% of the in vivo exposed and 94% of the in vitro exposed embryos were morphologically abnormal. Ultrastructural observations showed that exposure to AVYS in vivo or in vitro caused severe damage to the VYS endodermal epithelial cells with loss of cellular borders, reduction in the number and length of microvilli, and increased cellular inclusions; and some damage to PYS endodermal cells with increased blebbling and decreased cell number. Recovery was evident at 72 hr and complete by 96 hr. The Endocytic Index was significantly reduced in the VYS 24 and 48 hr after injecting AVYS into the pregnant rat but was not significantly different at 96 and 192 hr. Our results show that the AVYS antiserum damaged visceral endodermal epithelium experienced ultrastructural recovery with parallel functional recovery. These studies suggest that transient yolk sac placental ultrastructural damage and dysfunction was probably sufficient to cause irreversible damage to the developing embryo during early organogenesis. We conclude that the proximate effect of the AVYS was on the plasma membrane of the visceral endoderm and that decreased pinocytosis is a consequence of this effect.

Animals↗
PubMed1997

Inhibitory effects of thymus-independent type 2 antigens on MHC class II-restricted antigen presentation: comparative analysis of carbohydrate structures and the antigen presenting cell.

The role of thymus-independent type 2 (TI-2) antigens (polysaccharides) on the MHC-II-restricted processing of protein antigens was studied in vitro. In general, antigen presentation is inhibited when both peritoneal and splenic macrophages (M phi) as well as Küpffer cells (KC) are preincubated with acidic polysaccharides or branched dextrans. However, the inhibitory effect of neutral polysaccharides was minimal when KC were used as antigen presenting cells (APC). Morphological evaluation of the uptake of fluoresceinated polysaccharides clearly correlates with this selective and differential interference. Polysaccharides do not block MHC-I-restricted antigen presentation. Some chemical characteristics shared by different saccharides seem to be specially related to their potential inhibitory abilities: (i) those where two anomeric carbon atoms of two interlinked sugars and (ii) those containing several sulfate groups per disaccharide repeating unit. No polysaccharide being inhibitory in M phi abrogated antigen processing in other APC: lipopolysaccharide-activated B cells, B lymphoma cells, or dendritic cells (DC). Using radiolabeled polysaccharides it was observed that DC and B cells incorporated less radioactivity as a function of time than M phi. Morphological evaluation of these different APC incubated for extended periods of time with inhibitory concentrations of polysaccharides revealed intense cytoplasmic vacuolization in M phi but not in B cells or DC. The large majority of M phi lysosomes containing polysaccharides fail to fuse with incoming endocytic vesicles and delivery of fluid-phase tracers was reduced, suggesting that indigestible carbohydrates reduced the fusion of these loaded lysosomes with endosomes containing recently internalized tracers. It is suggested that the main causes of this antigen presentation blockade are (i) the chemical characteristics of certain carbohydrates and whether the specific enzymatic machinery for their intracellular degradation exists; and (ii) the different phagocytic abilities of distinct APC populations, fluid-phase pinocytosis and receptor-mediated saccharide uptake, and existence of a differential antigen-processing pathway in M phi and DC or B cells, which could be based on a polysaccharide-inhibited step present in M phi but unaffected or irrelevant in both B cells and DC.

Animals↗
PubMed1993

Nematolysosomes (elongate lysosomes) in rat hepatocytes: their distribution, microtubule dependence, and role in endocytic transport pathway.

The distribution of lysosomes in rat hepatocytes was examined by three-dimensional electron microscopy combined with acid phosphatase (ACPase) cytochemistry. In the 2-microns-thick sections observed under 200- or 1000-kV TEM, it was apparent that ACPase activity localized on elongate lysosomes (we refer to them as nematolysosomes) with a diameter of 70-100 nm and lengths of several micrometers, as well as spherical lysosomes and trans-Golgi cisternae. Though most spherical lysosomes were located within the pericanalicular region, nematolysosomes were widely distributed throughout the hepatocytes. Typically, it appeared that the nematolysosomes elongated from the subsinusoidal region to the pericanalicular-Golgi complex area and they frequently formed a network at the cell periphery along the sinusoidal front. Furthermore, the formation of nematolysosomes was independent of new protein synthesis, but highly dependent on the integrity of microtubules. After a 6-8 h colchicine treatment, nematolysosomes were shrunk and/or fragmented, becoming roughly spherical lysosomes scattered throughout the cells. Nematolysosomes recovered their normal profiles after 24 h due to the reversible effect of the drug on microtubules. When the hepatocytes were exposed to horseradish peroxidase (HRP) in vitro or in vivo, HRP was quickly sequestered in nematolysosome-like structures via pinocytosis from the sinusoidal surface and transported to an area near the Golgi complex. These findings raise the possibility that the nematolysosomes engage in microtubule-dependent transport of macromolecules from the sinusoidal circulation to the Golgi complex area.

Acid Phosphatase↗
PubMed1999

Cryptosporidium parvum infection in suckling rats: impairment of mucosal permeability and Na(+)-glucose cotransport.

Na(+)-glucose transport and transepithelial permeability were investigated during symptomatic acute cryptosporidiosis in newborn rats. The infection resulted in a significant (P < 0.01) decrease in the ileal short-circuit current and a nonsignificant fall in the transepithelial potential difference and conductance. In glucose-stimulated conditions, the rise in ileal short-circuit current and transepithelial permeability were significantly lower in Cryptosporidium parvum-infected rats than in controls (delta Isc = 3.24 +/- 1.21 microA.cm-2 vs delta Isc = 5.09 +/- 2.23 microA.cm-2 in infected and control animals, respectively; P < 0.001; delta PD = -0.35 +/- 0.13 mV vs delta PD = -0.44 +/- 0.14 mV for infected and control animals, respectively; P < 0.01). Electrical parameters were not affected by addition of the cyclooxygenase inhibitor indomethacin in either Cryptosporidium-infected newborn rats or controls. Horseradish peroxidase and mannitol flux studies demonstrated a significant decrease (P < 0.05) in transepithelial molecular permeability in infected enterocyte rats, HRP flux = 380, range 68-5570 ng.cm-2, and mannitol flux = 1.06, range, 0.34-1.44%.cm-2.min-1, compared with controls rats, HRP flux = 4446 range, 1121-124,363 ng.cm-2, and mannitol flux = 1.99, range, 0.57-5.09%.cm-2.min-1; P < 0.05. These effects could originate from C. parvum-induced alteration of intracellular trafficking of pinocytosis vesicles and therefore account for the decrease in permeability to solute and macromolecules, together with impaired transcellular nutrient transport, in suckling rats.

Animals↗
PubMed2001

Receptor-mediated endocytosis in an apicomplexan parasite (Toxoplasma gondii).

Endocytosis mechanisms are poorly known in apicomplexan parasites. Here, we show that extracellular tachyzoites of Toxoplasma gondii bind and internalize heparin-like sulfated glycans in a specific, saturable manner. Discrete binding of the glycan occurs at the anterior third of the tachyzoite, where it is rapidly concentrated inside single tubulo vesicular compartments that become multiple with time. The compound is held for several hours intracellularly with no apparent exocytosis or acidification. Incubation in the continuous presence of fluorescein isothiocyanate-conjugated heparin enhances the binding and internalization of this ligand by live tachyzoites. Two tachyzoite surface polypeptides exhibit strong binding and specificity for heparin, making them candidate receptors. Uptake of fluid-phase endocytic tracers occurs via nonspecific pinocytosis in the same region of the parasite cell, but with much lower efficiency. These observations show that extracellular tachyzoites can acquire molecules through both receptor-specific and fluid-phase endocytic mechanisms. Understanding the physiological relevance of these processes for the extracellular and intracellular stages of T. gondii may bring about direct targeting of the parasite by drug delivery into the tachyzoites.

Animals↗
PubMed1996

Immunolocalization of the oostatic and prothoracicostatic peptide, Neb-TMOF, in adults of the fleshfly, Neobellieria bullata.

The hexapeptide Neb-TMOF (H-NPTNLH-OH, trypsin modulating oostatic factor of the gray fleshfly, Neobellieria bullata)2 occurs in vitellogenic ovaries and is involved in negative feedback regulation of trypsin biosynthesis in the gut of late vitellogenic females. Polyclonal antisera were raised against the synthetic peptide and were used to identify and immunolocalize Neb-TMOF epitopes in different fleshfly tissues. Neb-TMOF-immunoreactive material first appears in the cortical layer of young vitellogenic oocytes and later spreads over the yolk granules. This suggests a pinocytosis with the three yolk polypeptides (vitellogenins). Controls treated with the preimmune sera or with anti-Neb-TMOF antiserum preadsorbed to Neb-TMOF peptide coupled to a solid phase support did not stain. There was no immunostaining in the central nervous system (brain and ventral nerve cord), the retrocerebral complex, the fat body, or the testes. Western blot analysis showed that the anti-Neb-TMOF antisera specifically recognize a putative hormone precursor polypeptide (Mr 75 kDa) from vitellogenic ovaries. This protein is virtually absent from the hemolymph. It is not immunologically related to the three yolk polypeptides, since it is not recognized by yolk polypeptides antisera. In adult females the ovary appears to be the only site of synthesis of Neb-TMOF and of its precursor. Immunopositive staining is found in the apical areas of ovarian follicle cells, suggesting these cells as a site of hormone precursor biosynthesis. This is the first demonstration that a protein colocalized with yolk proteins might act as a precursor for a folliculostatic hormone.

Animals↗
PubMed1994

GnRH agonist therapy in human ovarian epithelial carcinoma (OVCAR-3) heterotransplanted in the nude mouse is characterized by latency and transience.

We have previously documented the responsiveness of a cell line of human ovarian epithelial carcinoma (Bowman Gray 1) heterotransplanted in nude mice to treatment with the GnRH agonist Lupron-SR. In this study we used another human ovarian epithelial carcinoma cell line, OVCAR-3, and the human endometrial carcinoma cell line HEC-1A. After a latent period, OVCAR-3 tumors showed significant inhibition of growth on Days 17, 21, and 24 (P < 0.03) compared to controls. The effect was transient and did not persist beyond Day 24. HEC-1A tumors showed no inhibition of growth. Radioreceptor assay studies utilizing native radiolabeled GnRH and [D-Lys6]-GnRH revealed no specific GnRH receptors in any of the tumor samples (BG-1, OVCAR-3, HEC-1A, University of Nebraska cell line, and two fresh human ovarian epithelial tumor samples) compared to male rat anterior pituitary cells. Binding studies and the latency and transience of effect would suggest that the mechanism of action in this animal model may be indirect. This activity may be via altered circulating steroids, gonadotropins, cell-cycle regulatory events, or some other as-yet-undefined action related to GnRH agonist administration or indirectly via effects of the metabolic products of degraded GnRH agonist such as D-amino acids, which are incorporated into the cells by constitutive or adsorptive pinocytosis. This study confirms latency and transience of effect of GnRH agonist therapy on an in vivo model of ovarian cancer.

Animals↗
PubMed1978

Further evidence for a role of secretory component (SC) and J chain in the glandular transport of IgA.

These studies support the transport model depicted in Figure 3: Incorporation of J chains into dimeric IgA induces a configurational fit allowing complexing of IgA with SC available in the plasma membrane of serous secretory epithelial cells. This complexing on the surface of the cell stimulates pinocytosis, and the completed secretory IgA molecules are transported in cytoplasmic vesicles to the gland lumen. The same transport model can be applied for the external translocation of IgM.

Adolescent↗
PubMed1986

Pathophysiological aspects of blood-brain barrier permeability in epileptic seizures.

Blood-brain barrier (BBB) permeability to macromolecules was assessed during seizures induced by pentylenetetrazole, bicuculline, methoxypyridoxine, methionine sulfoximine, and kainic acid. It was observed that each convulsant induced a specific pattern of regional BBB opening. This was, however, only the case when systemic blood pressure (BP) rose with seizure onset. The analysis of regional cerebral blood flow revealed that a high increase in flow in rabbits with BP rise is related to the normal flow at rest in the single brain region, but not to BBB permeability. In rabbits without BP increase, regional flow increase was low but well modulated and is possibly a better indicator for neuronal activity. The ultrastructural analysis showed that macromolecular transport over the cerebrovascular endothelium is by pinocytosis, an neurotransmitter controlled process. It is suggested that seizure-induced regional BBB opening is determined by two factors: release of neurotransmitters due to the process of auto-regulation during peripheral pressure increase, and change in local neurotransmitter milieu due to the action of the convulsant and/or the seizure activity.

Animals↗
PubMed1983

Therapeutic considerations in blood-brain barrier disturbances.

Current methods of treatment of brain damage, as e.g. edema by steroids and barbiturates, have components which benefit the blood-brain barrier. Protection of the blood-brain barrier may result from: (a) prevention of endothelial lesions, perhaps pinocytosis (b) reduction of secondary necrosis formation, (c) interference with release, or activation of mediator compounds causing endothelial lesions such as: biogenic amines, free fatty acids, prostaglandins, free radicals, or kinins, (d) stabilization of lysosomal membranes, and (e) prevention of microcirculatory disturbances. Other methods, or compounds aiming at mechanisms of barrier damage have a therapeutic potential as shown with regard to indomethacin, free radical scavengers, or phenothiazines. However, further studies appear necessary to demonstrate the benefit of these compounds under clinical circumstances. Reversible opening of the blood-brain barrier may be considered as a therapeutic approach to provide access of drugs to brain tissue which are normally excluded by the barrier.

Animals↗
PubMed1983

Morphology of cerebral endothelium and astrocytes as determinants of the neuronal microenvironment.

The morphological features of the blood-brain barrier to macro-molecules under normal and perturbed conditions are reviewed in the context of some recent investigations. The electric charge on molecules of horseradish peroxidase (HRP) affect its pinocytosis and intracellular fate which pertains to problems of distinguishing endocytosis from vesicular transport across endothelium. When the barrier is opened, the number of pits, vesicles and tubules increases. Such cerebral endothelium resembles normal endothelium of certain fish where numerous membrane invaginations do not signify vesicular or tubular transport. However, such transport has not been entirely ruled out in reactive endothelium. Another route of exudation during barrier opening may be via patent endothelial junctions, especially during intravascular infusion of hyperosmotic solutions. The permeability of the tight junctions, however, is not reflected unequivocally by its intramembranous structure. Although astrocytes do not provide a barrier to the extracellular flow of solutes, their ubiquity may enable them to modify the composition of perineuronal fluid. Their orthogonal arrays of intramembranous particles may be involved. The number of assemblies increases in astrocytes reacting to trauma and to the extracellular accumulation of lactate and CO2. The assemblies might thus participate in the transport of catabolites to and from extracellular fluid.

Animals↗
PubMed1990

Presence of transendothelial channels in cerebral endothelium in chronic hypertension.

In this model hypertension developed as early as 1 wk. post-surgery and was associated with reduction in Ca2(+)-ATPase activity in cerebral vessels indicating that abnormalities in ionic calcium in vessel walls occur early in the evolution of hypertension. This study supports previous observations that cerebral cortical arterioles develop increased permeability to endogenous plasma proteins in chronic hypertension. The principal mechanism resulting in this increased permeability is enhanced pinocytosis. Ca2(+)-ATPase localisation in endothelial pinocytotic vesicles helped to localise transendothelial channels in occasional vessels of hypertensive rats. The latter findings reinforce the concept that in pathologic states associated with cerebral oedema, pinocytotic vesicles fuse to form transendothelial channels which transport plasma proteins into brain.

Animals↗
PubMed1990

Cerebrovascular permeability in acute hypertension: effect of flunarizine.

The pattern of Evans blue extravasation in the brain in norepinephrine-induced acute hypertension is similar to our previous observations using horseradish peroxidase as a tracer. Pretreatment with flunarizine IV resulted in significant reduction of RISA leakage in all regions of the brains of acutely hypertensive rats. The reduction in RISA leakage in the drug-treated hypertensive group is not attributable to differences in the blood pressure elevations which were not significantly different in both groups. These studies suggest a role for calcium in the increased endothelial permeability occurring in cerebral vessels in acute hypertension. Further morphological studies are required to determine whether flunarizine reduces permeability by decreasing pinocytosis.

Acute Disease↗
PubMed1990

A microstructural study of oedema resolution.

The infusion model was used to investigate the resolution mechanism of vasogenic brain oedema. HRP dissolved in autoserum was infused into the white matter of cats. The infused protein in the oedema fluid seemed not only to be absorbed by pinocytosis or phagocytosis, as has been reported previously, but also to be quickly washed out via the perivascular space of the post-capillary venules. Smaller molecules such as HRP moved faster than serum albumin in these spaces after the infusion pump was turned off. Rapid flow of extracellular fluid via the perivascular space may play an important role on the resolution process of vasogenic brain oedema by accelerating diffusion.

Animals↗
PubMed1995

The interaction of gadolinium complexes with isolated rat hepatocytes.

The lanthanide metal, gadolinium, is currently used in contrast agents for magnetic resonance imaging. We have performed a study of the interaction between isolated rat hepatocytes and 153Gd complexed to diethylene-triamine pentaacetic acid (DTPA) or to DTPA-albumin conjugates. The study shows that isolated hepatocytes are able to take up both types of 153Gd complexes. The 153Gd-DTPA-albumin complexes are apparently taken up by pinocytosis, and possibly receptor-mediated endocytosis and/or adsorptive endocytosis, whereas the uptake mechanism of 153Gd-DTPA is unknown. The 153Gd-DTPA-albumin complexes, but not the 153Gd-DTPA complex, are degraded by the cell. The degradation is inhibited by ammonium chloride. Gadolinium is slowly released back to the medium after loading of the cells with both complex types. In the experiments reported here no evidence of any adverse effects on the hepatocyte resulting from exposure to the 153Gd-complexes were observed.

Albumins↗
PubMed1989

Ultrastructural study of micro-blood vessels in human brain tumors and peritumoral tissue.

Ultrastructural and tracer studies have demonstrated that vasogenic edema, a serious complication of brain tumor is the result of increased permeability of tumor vessels. However, not much information is available on the alterations in the vessels in the peritumoral areas. Therefore, we studied the ultrastructural changes in the tumor micro-blood vessels (MBVs) in 20 cases of glioma and compared these with the changes in the peritumoral MBVs in 10 of these cases. The tumor MBVs showed remarkable structural changes, viz, increase in pinocytotic vesicles, large vacuoles and microvilli in the endothelial cells, varying degrees of endothelial attenuation and fenestration, an occasional partially or completely opened-up junction and some pale and edematous endothelial cells, which can adequately explain their increased permeability. The peritumoral MBVs also showed evidence of increased permeability in the form of increased pinocytotic vesicles, large vacuoles and microvilli associated with pale and edematous cytoplasm of some endothelial cells. Thickened multilayered basement membrane, absence of ensheathment of capillary basement membrane by astrocytic cell processes and widened perivascular space were observed in both tumoral and peritumoral MBVs. An interesting observation was that in the peritumoral MBVs, the pinocytotic vesicles were most conspicuously seen on the abluminal side of the endothelial cells often fused with the abluminal plasma membrane. Although a static study like this cannot indicate any definite direction of movement of fluid, we feel that the occurrence of reverse pinocytosis is a distinct possibility in the peritumoral MBVs and that it may be an important means of resorption of edema fluid.

Basement Membrane↗
PubMed1983

Cytophysiological aspects of digestion and storage in the liver of a scorpion, Androctonus australis (Arachnida).

The liver of a scorpion, Androctonus australis (Arachnida), was examined electron-microscopically and cytochemically, emphasizing correlations between structure, cytochemistry and physiology. The liver consists of digestive diverticula and interstitial tissue. Digestive diverticula are composed of basophilic cells and digestive cells. Basophilic cells produce exoenzymes. Digestive cells ensure intracellular digestion of nutrients absorbed by pinocytosis and store glycogen, lipids and mineral salts; the wastes of the digestive process (guanine, uric acid, mineral elements, pigments) are concentrated in "brown body vacuoles" which are ejected into the lumen of the diverticula. The interstitial tissue stores glycogen and lipids; it contains many lysosome-like organelles rich in iron. Fasting induces a decrease of the ratio of the volume of the diverticula to that of the interstitial tissue, a slow disappearance of the reserves in both diverticula and interstitial tissue, an increase of synthesis in the basophilic cells, and a decrease of the number of vacuoles in the digestive cells. The digestive mode of the scorpions associates a primitive intracellular process with an advanced extracellular process. The interstitial tissue can be considered as homologous to the adipose tissue of insects and myriapods, although it is devoid of urate cells. The excretion of guanine and uric acid has a peculiar meaning, because these purine wastes do not come from endogenous catabolism.

Animals↗