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Biomedical subjects

J Molnar

Publications and source records attributed to J Molnar.

At least 37 records · Page 2Linked to original sources
PubMed1993

Morphine amplifies norepinephrine (NE)-induced LH release but blocks NE-stimulated increases in LHRH mRNA levels: comparison of responses obtained in ovariectomized, estrogen-treated normal and androgen-sterilized rats.

In these studies we examined the temporal effects of intracerebroventricular (i.c.v.) infusions of norepinephrine (NE) on plasma LH and on LHRH mRNA levels in the organum vasculosum of the lamina terminalis (OVLT) and in neurons located in the rostral (r), middle (m) and caudal (c) preoptic areas (POA) of ovariectomized, estrogen-treated rats. Thereafter, we compared these responses to those which occur in androgen-sterilized rats (ASR). NE infusions not only increased plasma LH concentrations but within 1 h after NE, LHRH mRNA levels also were increased significantly in the OVLT and rPOA but not in the mPOA or cPOA. By 4 h, these message levels still were elevated in the OVLT and rPOA and they now also were significantly higher than control values in the mPOA and cPOA. While NE also increased LH secretion in ASR, the plasma LH concentrations obtained were markedly blunted compared to control values. Moreover, NE infusions did not alter single cell levels of LHRH mRNA in any region of the rostral hypothalamus. Previously, we have reported that morphine (s.c.) markedly amplifies NE-induced LH release and questioned whether these responses are accompanied by concomitant augmented increases in LHRH mRNA levels. Morphine alone did not affect basal LHRH mRNA or plasma LH levels. However, when rats were pretreated with morphine (-15 min) and NE was infused i.c.v. at 0 time, significant amplification of LH release occurred but, unexpectedly, morphine completely blocked NE-induced increases in LHRH mRNA levels in all of the neurons we examined. Morphine also amplified LH release in ASR but these responses were significantly less than those obtained in control rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Androgens↗
PubMed1990

[Experiences in the diagnostic and surgical video-endoscopy of the thoracic cavity].

Thoracoscopy is a well-established method for diagnostic evaluation of various manifestations of intrathoracic disease, with a high degree of sensitivity and specificity. While a rigid telescope is generally used, we have modified this technique by connecting a CCD-chip-camera to the thoracoscope to achieve direct visualization for observers. 52 patients were examined in this manner, 18 for diagnostic reasons and 35 for therapeutic purposes. The mean age of the patients was 55 years, ranging from 26 to 84 years. Potential risk factors associated with this modified endoscopic procedure were analyzed. Mortality was zero, but complications occurred in 5.6%. Surgical re-intervention was necessary in two cases for control of postoperative intrathoracic hemorrhage; in another case the introductory trocar caused superficial injury to the lung without further consequences. In these complications extensive scarring of the pleura was noted. It is only natural that the rate of complications is closely associated with a learning period during which the operative technique is improved. Following adequate mastery of the technique our goal is presently to treat spontaneous pneumothorax and malignant effusions by thoracoscopy. We strongly recommend treatment of malignant effusions and pneumothorax by thoracoscopy as a primary procedure and not secondarily when blind attempts at pleurodesis have failed and given rise to partially obstructive adhesions.

Adult↗
PubMed1988

Demonstration that some of the nonhistone proteins, inducible to translocate into the nucleus, are glycosylated.

Con A, NaF, and eserine (lysosomotropic agents) induced marked translocation of acidic [3H] nonhistone proteins (NHP) from the cytoplasm to the nucleus in lymphocytes prelabeled with [3H]-2-mannose. The nuclear [3H] NHP contents were 38-120% higher in cells treated with these agents than in control cells. Tunicamycin, a strong inhibitor of N-glycosylation via the dolichol pathway, caused a concentration-dependent inhibition of [3H]-2-mannose incorporation into the nuclear [3H] NHP. Considerable amounts of nuclear [3H] NHP from lymphocytes labeled with either [3H]-2-mannose or [3H] leucine, bound specifically to Con A-Sepharose and could be eluted by alpha-methyl mannoside. Con A and NaF caused also nuclear translocation of acidic [3H] NHP in cells labeled with [3H] glucosamine, [3H] galactose, or [3H] fucose. Fractionation of the nuclear proteins by isoelectric focusing in a pH gradient of 2.5-6.5 showed that multiple species of acidic NHP were labeled with each of the four 3H-sugars. These results indicate that a fraction of the acidic nuclear NHP are N-glycosylated proteins and that gene activation and mitogenesis are associated with the translocation of these glycoproteins to the nucleus. Considering the known intracellular traffic of nascent glycoproteins our results suggest that at least some of the acidic NHP are synthesized and glycosylated in the endoplasmic reticulum and the Golgi (secretory pathway). It is likely that these proteins, after completion of synthesis and glycosylation, emerge from the trans-stack of the Golgi packaged in vesicles and accumulate in the cytoplasm. Induction of nuclear translocation of such NHP by various agents may be mediated by a vesicular transport mechanism.

Cell Nucleus↗
PubMed1988

Expression of polymorphic B-cell antigens on human kidneys.

We have examined the expression on a panel of 22 human kidneys of polymorphic B-cell determinants recognized by mouse monoclonal antibodies. Monoclonal antibodies from a mouse immunized with an antigenic preparation from a DR4 positive B-cell line reacted preferentially with kidneys from DR4 positive donors (p less than 0.005), and the pattern of reactivity with kidney tissues was similar to that of antibodies to monomorphic determinants of class II. However, these antibodies did not show clear specificity for DR4 on lymphocytes in standard serological analyses. These results provide evidence for the expression of polymorphic class II determinants on human kidneys. Reasons for the differences in the apparent specificities of the monoclonal antibodies when tested on kidney sections and lymphocytes are discussed.

Absorption↗
PubMed1987

Definition of fibronectin-mediated uptake of gelatinized latex by liver slices and macrophages.

These studies show that both liver slices and macrophages carried out fibronectin concentration-dependent uptake of 125I-labeled gelatin-coated latex (test latex). Lack of phagocytosis of test latex by liver slices was shown directly by electron microscopy and indirectly by trypsin treatment, which caused the release of all test latex taken up in response to fibronectin. Inhibitors of phagocytosis did not alter this uptake. On the other hand, trypsin released only a portion of test latex from macrophages. Inhibitors of phagocytosis did not effect the released radioactive particles from macrophages but greatly reduced the trypsin-resistant radioactivity, taken as representing phagocytized particles. Opsonization of test latex with fibronectin did not require heparin but its association with liver slices occurred only in the presence of heparin. Macrophages, however, readily bound and internalized the opsonized test latex and heparin only potentiated these reactions. Gelatin competed with test latex for fibronectin for opsonization, but did not inhibit binding and phagocytosis of fibronectin-test latex complexes. Finally, soluble fibronectin-gelatin complexes did not compete for binding and phagocytosis of fibronectin-test latex complexes. Thus, fibronectin concentrated on the surface of latex is preferred for interaction with the fibronectin receptor of macrophages. Gelatin, however, was not essential for this reaction, because fibronectin directly coupled to latex was also readily taken up.

Animals↗
PubMed1987

Evidence for the recycling nature of the fibronectin receptor of macrophages.

Plasma fibronectin (pFN) has been shown to mediate phagocytosis of several types of artificial particles and tissue debris by macrophages. In the present investigation some of the dynamic aspects of this receptor-mediated cellular process have been studied. Plasma fibronectin did not bind specifically to fibronectin (FN)-receptors of rat peritoneal macrophages at either 4 degrees C or 37 degrees C. On the other hand, pFN aggregated on the surface of gelatin-coated latex beads (gLtx) and 125I-labeled pFN covalently coupled to latex beads (pFN-Ltx) bound strongly to macrophages at both temperatures. Both of these particles were also internalized at 37 degrees C. Treatment of macrophages by chymotrypsin, thermolysin, or trypsin in a protein-free tissue culture medium did not affect either of the above reactions; however, pronase treatment strongly reduced both the binding and internalization of the pFN-coated particles. The pronase-treated macrophage monolayers in time regained their ability to bind and internalize pFN-gLtx when incubated in fresh tissue culture medium. Such recovery, however, did not take place when the medium contained cycloheximide. On the other hand, phagocytosis of pFN-gLtx was not affected directly by cycloheximide with untreated macrophages; this suggests that the FN-receptor recycles during sustained phagocytosis. This assumption was substantiated by the observations that some of the established lysosomotropic amines--i.e., chloroquine, dansylcadaverine, and dimethyldansylcadaverine--caused total inhibition of internalization without affecting the binding of particles to macrophages. Furthermore, chloroquine protected the FN-receptors against destruction by pronase. Together these results suggest that macrophage receptors for FN are protein, present both on the cell surface and intracellularly, and recycle between the plasma membrane and intracellular sites during phagocytosis.

Animals↗
PubMed1986

The effects of amino acids on protein degradation and translocation of non-histone proteins to the nucleus in lymphocytes.

Tryptophan, phenylalanine and leucine have two parallel effects in cultured lymphocytes, they inhibit cellular proteolysis and increase the translocation of non-histone proteins to the nucleus. The latter is associated with an increased cellular binding of [3H]actinomycin D, indicating an altered structure of chromatin. The amino acids also inhibit the cellular uptake of [3H]chloroquine, suggesting that inhibited protein degradation is lysosomal. Several amine catabolites of tryptophan and phenylalanine, some of which are known to play a role as biogenic amines, have similar actions, and can explain, at least in part, the effects of their parent amino acids. Fractionation of the nuclear 3H-labeled non-histone proteins according to pH 2.5-6.5 shows that such proteins with a high rate of degradation in untreated cells correspond to the 3H-labeled non-histone proteins with a high rate of translocation in tryptophan treated cells. These data suggest that the degradation and the translocation of the non-histone proteins are linked and that the increased translocation of the non-histone proteins to the nucleus may be the consequence of inhibited lysosomal degradation of these proteins by the amino acids.

Amino Acids↗
PubMed1985

The effect of pentoxifylline on the energy metabolism of ischemic gerbil brain.

Pentoxifylline decreases the cerebral edema resulting from cortical freezing lesions in cats, produces mitochondrial hypertrophy with preservation of structure in gerbils, and increases survival rate in gerbils rendered ischemic by temporary bilateral carotid occlusion. Since all these findings may be related to energy metabolism, the effect of the drug on postischemic cerebral phosphocreatine and ATP concentrations and on cytochrome oxidase activity has been studied. Brain slices prepared from animals subjected to bilateral carotid occlusion for 30 min and treated with pentoxifylline at release of occlusion, then allowed 3 h for recovery, exhibited higher concentrations of ATP and higher levels of cytochrome oxidase activity than did those of the untreated animals.

Adenosine Triphosphate↗
PubMed1984

Interaction of plasma fibronectin (pFN) with membranous constituents of peritoneal exudate cells and pulmonary macrophages.

The prominent role of plasma fibronectin (pFN) in the host defense system as an opsonin for gelatin (collagen)-coated colloids has been established. In the present study we investigated the interaction of pFN and membrane isolates from cells devoid of collagen, as well as several tissues. In a liver slice assay system it was shown that subcellular membrane fractions from lung macrophages, peritoneal exudate cells, spleen, tests, and liver were able to competitively inhibit the pFN-mediated uptake of 125I-gelatin coated latex beads (gLtx) at low concentrations. Endocytosis of 125I-labeled membrane isolates by macrophage monolayers was also promoted by addition of pFN. In an attempt to characterize the membrane component(s) interacting with pFN, it was found that mild extraction procedure with 1 M KBr could release a significant amount of this inhibitory activity. Further studies demonstrated that the agent(s) responsible for inhibition of gLtx uptake was heat sensitive, not altered by trypsin treatment, and did not contain actin, a protein known to interact with pFN. This work indicates that pFN interacts specifically with an as yet unknown membrane component(s) and that such interaction will promote clearance of cellular debris by macrophages. This suggests that pFN may be an important opsonin for the reticuloendothelial system in clearance of collagenous and noncollagenous cellular debris once they are exposed to interact with it.

Animals↗
PubMed1983

Enzymatic modifications of human plasma fibronectin in relation to opsonizing activity.

Plasma fibronectin is one of the largest plasma proteins (Mr approximately 440 000), comprising two approximately equal polypeptide chains which are held together by a disulfide linkage near the C-terminal end of the molecule. The binding of gelatinized latex beads to liver slices as well as the internalization of these particles by macrophages, in the presence of heparin, is greatly enhanced by fibronectin. The question as to whether the entire covalent structure of fibronectin was necessary for opsonizing activity was approached by limited proteolytic degradations of the molecule. Patterns of controlled digestion with trypsin, cathepsin D, Staphylococcus aureus protease, and plasmin all indicate that the minimal unit necessary for retention of opsonic activity is some large (Mr 200 000 and 190 000) single-chain entity. Treatment with plasmin proved to be the most reliable procedure for generating the active split product which could be readily separated from the inactive, disulfide-containing C-terminal fragment. Incorporation of dansylcadaverine into plasma fibronectin (3.5 mol/mol of protein) by fibronoligase (coagulation factor XIIIa) did not affect the opsonic activity of the protein.

Cathepsin D↗
PubMed1983

Wound healing accelerated by Staphylococcus aureus.

While comparing the effects on wound healing of a heated scalpel with those of the cold scalpel, we discovered that inoculation of rat skin incisions with a strain of Staphylococcus aureus dramatically accelerated the gain in wound strength. The accelerating effect was evident four days postoperatively, was maximal at seven to ten days, and was still present at 28 days. The accelerating effect was correlated with the number of S aureus organisms introduced into the wound, and was found in conventional rats and rats germ free up to the time of monocontamination with S aureus. There was no evidence of infection on gross examination; on histologic examination an occasional microabscess was seen in some rats. There may be both local and systemic mechanisms underlying the S aureus accelerating effect. Seven strains of S aureus with varying characteristics demonstrated the wound-healing accelerating effect. In sharp contrast, Staphylococcus epidermidis (three strains), Staphylococcus hominis (one strain), and Pseudomonas aeruginosa (two strains) did not show this effect. The increases in wound healing due to S aureus were substantially greater than reported previously for any nutritional supplement, drug, or other chemical or physical agent.

Animals↗
PubMed1983

The mechanism of natural binding of bacteria to human lymphocyte subpopulations.

Some bacteria bind naturally to human lymphocyte subpopulations. Here we investigated the nature of the interacting factors" on bacterial cells and on lymphocytes. First, surface Ig was not involved in the binding of B. melitensis to B cells, since capping of surface Ig did not affect the binding of this bacteria. We put forward the hypothesis that the binding is due to an interaction between a protein (probably a lectin) on the lymphocyte surface and a carbohydrate on the bacteria. The following observations were consistent with this hypothesis: (1) the binding of B. melitensis to B cells was prevented by alpha-methyl-D-mannoside (alpha-MM) but not by other sugars; (2) the binding of B. melitensis to B cells was prevented by pretreatment of the peripheral blood lymphocytes (PBL) with 257 mM of alpha-MM but pretreatment of the bacteria had no effect; (2) an Escherichia coli mutant (strain 2023) which binds to B cells and part of the T cells was also agglutinated by Concanavalin A (Con A) but the nonbinding parental strain was not; the binding of this mutant to B cells was also inhibited by 257 mM of alpha-MM; (4) bacteria that bind to human lymphocytes were agglutinated at high titers by various plant lectins while those that do not bind were not agglutinated or were agglutinated only at low titers; (5) bacteria that bind to B cells as well as those that bind to B and T cells all were agglutinated by Con A, Lens culinaris agglutinin and Pisum sativum agglutinin, whose carbohydrate specificities were alpha-D-mannosyl- and alpha-D-glucosyl-residues; (6) the "receptors" on lymphocytes but not those on bacteria were sensitive to pronase digestion; and (7) bacteria still bound after being heated at 121 degrees C or being fixed with formaldehyde. Thus, we suggest that one of the mechanisms by which bacteria bind to lymphocytes may be by the interaction between a lectin on the lymphocyte and a carbohydrate on the bacteria.

Agglutination↗
PubMed1982

A hemostatic scalpel for burn debridement.

We studied excision of burns with a new heated scalpel. The disposable blade resemble conventional scalpel blades, except that their edges can be heated and the temperature controlled within narrow limits. The control mechanism compensates "instantaneously" for varying losses of heat depending on the vascularity of the tissues and rate of cutting. Cutting is done by the blade's sharp edge and hemostasis results from direct transfer of heat; no electric currents are generated in the tissues. The blades can be fashioned in variety of shapes and sizes, including those suitable for tangential excisions. The heated scalpel allows excision of third-degree burns in pigs and humans with much smaller loss of blood than when the usual cold surgical scalpel is used. Skin grafts applied immediately after excisions with the heated scalpel had excellent rates of success, similar to those of grafts applied immediately after excisions with the cold scalpel.

Animals↗
PubMed1981

Phagocytosis-promoting activity of avian plasma and fibroblastic cell surface fibronectins.

The purpose of this investigation was to determine whether fibronectin preparations from both chicken plasma and cell surface of fibroblasts can promote phagocytosis of gelatin-coated latex particles. Chicken plasma fibronectin was isolated (a) by ammonium sulfate fractionation, chromatography on Sepharose-4B followed by purification on a Sepharose-4B-heparin column; (b) by affinity chromatography on a Sepharose-4B-rat-antifibronectin column; (c) by affinity chromatography on Sepharose-4B-gelatin followed by molecular sieve separation on Sepharose-CL4B; (d) by a dual affinity chromatographic method using a Sepharose-4B-gelatin column and a Sepharose-4B-heparin column. Chicken cell surface fibronectin from fibroblast cultures was purified by ammonium sulfate precipitation followed by chromatography on Sepharose-CL4B. The purity of preparations was examined by polyacrylamide gel electrophoresis in the presence of sodium dodecylsulfate; all samples showing high purity. The opsonic activities of the preparations were measured by the uptake of 125I-labeled gelatin coated latex particles in conjunction with rat liver slice, and peritoneal macrophage monolayer systems. Both the plasma fibronectin and cell surface fibronectin preparations showed substantial opsonic activities in the test systems. Fresh chicken plasma did not reveal any phagocytosis promoting activity due to the presence of some unidentified inhibitor(s). The results showed that an opsonically active protein can be isolated from chicken plasma or serum and this protein is identical to plasma fibronectin. Furthermore, it could be concluded that cell surface fibronectin from chicken fibroblasts also can serve as an opsonin for gelatin coated particles.

Animals↗