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Biomedical subjects

A Schwartz

Publications and source records attributed to A Schwartz.

At least 325 records · Page 18Linked to original sources

Pathology of allergic diseases.

An allergic disease may develop in any organ or system. The respective etiological factors include foreign proteins, infectious agents such as various microbes, viruses, moulds, parasites, chemical compounds often in the form of drugs usually designated as haptens, polysaccharides, benign and malignant neoplasms. Of the factors operating in the causal pathogenesis of such diseases the most important one is an exaggerated formation of antibodies, which appears to be uncontrolled and occurring irrespective of the demands of the organism. The essential morphological features in allergic inflammation are rather variegated, their diagnostic value differing in a wide range but being never absolute. The above features include eosinophilic leucocytes, allergic arteritis and phlebitis, fibrinoid necrotic glomerulonephritis, histiocytic granulomatous inflammation or histiocytic granuloma. Granulomatous capsulitis and trabeculitis affecting the spleen and lymph nodes are believed to be of major diagnostic significance. The immunofluorescent and immunoperoxidase methods and electron microscopy are important diagnostic tools. It has been generally acknowledged that many drugs operate as antigens. They may cause death of the respective patient, but allergic manifestations may subside after withdrawal of such drugs. On occasion they operate as a trigger mechanism with the allergy progressing even after treatment had been interrupted. Therefore they have been receiving extreme attention. Our collection of cases a case of giant-cell myocarditis following sulfamethoxypyridazine, anaphylactic shock has been reported to occur after intravenous administration of novocaine, and generalized cutaneous vasculitis developed in the same patient during the subsequent phase. A similar cutaneous finding was reported to have developed after penicillin injection, granulomatous inflammation developed owing to sulfonamide treatment. Allergic tumour-like lymphadenitis developed after administration of anti-anthracic serum; an anticonvulsive syndrome developed after hydantoinate administration. The latter consisted of generalized exanthema, hepatomegaly, splenomegaly and generalized lymphadenopathy. The lymph nodes showed tumour-like lymphadenitis mimicking lymphogranuloma or reticulosis. Allergic diseases appear as either isolated organ lesions or systemic diseases. Thus, isolated and systemic polyarteritis nodosa, isolated nasal, pulmonary or systemic Wegener's granulomatosis have been recognized. Temporal arteritis has been recognized as a localized form of systemic giant-cell arteritis. The haemolytic-uraemic syndrome appears to be a milder variety of thrombotic thrombocytopenic purpura. Allergic diseases or manifestations occasionally affect two or more organs or systems.(ABSTRACT TRUNCATED AT 400 WORDS)

Humans↗

Controlled, double-blind study of iosimide, a new, nonionic, monomeric contrast medium, and ioxaglate in cerebral angiography.

Iosimide is a new synthetic, nonionic, monomeric contrast medium in which a new substance, triiodine-trimesine acid, is used. It has definite advantages compared with the basic substances used in the past, diaminobenzoic acid and monoaminoisophthalic acid. Due to the high stability, the possibility of the formation of toxicologically questionable, free nuclei amino compounds disappears. Only the slightest probability of a cross-reaction with present antibodies exists, because of the low frequency in the environment. On the basis of the hydrophilic structure of the side chains, there is only a slight chemotoxicity. In a controlled, double-blind study on 100 randomized patients iosimide was tested in cerebral angiography against ioxaglate. Ioxaglate is an ionic contrast medium, popular because of its low osmolality. In this study iosimide exhibited no differences in comparison with ioxaglate with respect to the contrast, the neurological status or the liver or renal tolerance. In examining cardiovascular tolerance there is only a slight tendency toward liver changes with iosimide. Examination of the general tolerance, however, shows a statistically significant lower incidence of sensation of heat and pain with iosimide than with ioxaglate.

Adult↗

[Eosinophilic histiocytic granuloma of the vulva and cervix].

In a patient aged 29 a recurrent histiocytic granuloma developed in vulva, vagina and cervix. The patient was treated by cervical resection followed by irradiation. Langerhans cells with Birbeck granules in plasma of the cells, besides multiple eosinophilic leucocytes were evidenced by electron microscope. The eosinophilic histiocytic granuloma is suggested to be a benign variety of histiocytosis X, whose basic cellular component is the Langerhans cell. Eosinophil leucocytes represent a local immune response in the benign variety of histiocytosis X.

Adult↗

Insulin-like growth factor II mRNA expression in human breast cancer.

Insulin-like growth factor II is a growth factor important in fetal development. Several cancer tissues and cell lines have been reported to express IGF-II and rat IGF-II is mitogenic for breast cancer cell lines. Using Northern analysis and ribonuclease protection assays, IGF-II mRNA was detected in normal fibroblasts and in the established breast cancer cell line, T47D. In this cell line, steady state levels of IGF-II message were increased by treatment with estradiol. 10 nM IGF-II, purified from human serum, was mitogenic for breast cancer cell lines. In vitro, IGF-II may act as an autocrine growth factor for some cell lines. RNA derived from breast cancer, pathologically normal breast tissue, and benign breast disease also contained IGF-II mRNA. When paired samples of normal and cancer tissue were obtained from the breast of the same patient, the level of IGF-II mRNA expression in the normal tissue was at least that found in the cancer. This is consistent with previous observations that show IGF-II is expressed in mesenchyme. These findings suggest that in breast cancer IGF-II is produced by stromal tissue elements and potentially by the malignant epithelial cells. Therefore, IGF-II may function as an autocrine or a paracrine growth factor in different breast tumors.

Blotting, Northern↗

Receptors for calcium antagonists.

Calcium antagonists have been divided into 3 different subclasses represented by nifedipine, verapamil and diltiazem. These drugs have different pharmacologic effects and are not interchangeable. Previous studies suggested that all calcium antagonists bind to a 170 kd polypeptide (now called the alpha 2 subunit of the voltage-dependent calcium channel). The apparent molecular weight of this polypeptide characteristically decreased from 170 to 140 kd upon disulfide reduction as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Recent studies demonstrated that calcium antagonists bind to a previously unrecognized 165 kd polypeptide (alpha 1 subunit) that does not change its electrophoretic mobility on disulfide reduction. Because of their similar molecular weights, the 2 polypeptides may overlap each other on polyacrylamide gels. The primary structure of both polypeptides clearly shows, however, that they are different from each other and only the alpha 1 subunit has the features expected of an ion channel.

Calcium Channel Blockers↗

Sequence and expression of mRNAs encoding the alpha 1 and alpha 2 subunits of a DHP-sensitive calcium channel.

Complementary DNAs were isolated and used to deduce the primary structures of the alpha 1 and alpha 2 subunits of the dihydropyridine-sensitive, voltage-dependent calcium channel from rabbit skeletal muscle. The alpha 1 subunit, which contains putative binding sites for calcium antagonists, is a hydrophobic protein with a sequence that is consistent with multiple transmembrane domains and shows structural and sequence homology with other voltage-dependent ion channels. In contrast, the alpha 2 subunit is a hydrophilic protein without homology to other known protein sequences. Nucleic acid hybridization studies suggest that the alpha 1 and alpha 2 subunit mRNAs are expressed differentially in a tissue-specific manner and that there is a family of genes encoding additional calcium channel subtypes.

Amino Acid Sequence↗

Effect of calcium channel modulators on isolated endothelial cells.

Indirect evidence, using organic calcium channel modulators suggests that calcium channels exist in endothelial cells. Using freshly prepared and cultured bovine aortic endothelial cells, we have studied the effect of calcium channel modulators on Fura-2 fluorescence and have examined the binding of the dihydropyridine, (+)[3H]PN200-110. In both isolated primary and cultured cells, external calcium (0.5-2 mM) and bradykinin (10(-8) M) increased the intracellular calcium concentration. In cultured cells, the increase in calcium was not significantly attenuated by preincubation with nitrendipine (10(-8) M) or d-cis-diltiazem (10(-6) M). The calcium agonists (-)Bay k8644 and (+)202-791 had no effect on intracellular calcium concentration, but other agonists including ATP (10(-4) M) and thrombin (1.5 micrograms/ml) significantly increased the calcium concentration. Competition binding studies with (+)[3H]PN200-110 indicated specific binding of this ligand with a KD of 57 nM and a Bmax of 2.1 pmol/10(6) cells. While these data do not provide convincing evidence for the existence of calcium channels in cultured or fresh bovine aortic endothelial cells, explanations may yet reconcile our observations with the presence of calcium channels in these cells.

Adenosine Triphosphate↗

Effects of isosorbide dinitrate and diltiazem on Ca2+ flux and contraction in artery.

We studied the effects of isosorbide dinitrate and diltiazem on histamine-stimulated 45Ca fluxes and contractions of isolated porcine coronary artery. Isosorbide dinitrate was slightly more potent as an inhibitor of intracellular compared to extracellular calcium-dependent contraction. Isosorbide dinitrate inhibited histamine-stimulated calcium efflux and intracellular calcium-dependent contraction over similar concentration ranges. Isosorbide dinitrate partially inhibited histamine-stimulated calcium influx, but this effect was significant only at high concentration and correlated weakly with inhibition of contraction that was dependent on extracellular calcium. Diltiazem more potently inhibited extracellular vs. intracellular calcium-dependent contraction. Diltiazem partially inhibited histamine-stimulated calcium efflux and intracellular calcium-dependent contraction to similar extents (55-60%) and produced similar concentration-response relationships for inhibition of histamine-stimulated calcium influx and extracellular calcium-dependent contraction. The data suggest that alterations of cellular calcium metabolism are major mechanisms of vascular smooth muscle relaxation by isosorbide dinitrate and diltiazem, but that the specific alterations differ for the two drugs. Isosorbide dinitrate may inhibit contraction primarily by enhancing intracellular calcium sequestration, but possibly also by inhibiting agonist-stimulated calcium influx at high isosorbide dinitrate concentrations. Diltiazem primarily inhibits stimulated calcium influx, but may also inhibit intracellular calcium release.

Animals↗

Cyclic AMP-dependent and cyclic AMP-independent actions of a novel cardiotonic agent, OPC-8212.

Possible cAMP-dependent and cAMP-independent mechanisms of action for the cardiac effects of OPC-8212, a novel piperazinyl-quinolinone derivative, were evaluated. OPC-8212 was tested for in vitro potency as an inhibitor of soluble bovine cardiac phosphodiesterases using a rapid isolation and assay method involving monoclonal antibodies that distinguish among isozymes. The drug was selective for a low-Km, cGMP-inhibited phosphodiesterase (CGI-PDE) with an IC50 (half-maximal inhibition concentration) of 7.4 mumol/l when measured at a substrate level of 0.35 mumol/l cAMP. Under the conditions used, sulfolane, the solvent for OPC-8212, did not affect CGI-PDE activity. In electrophysiological measurements, OPC-8212 prolonged the action potential duration in canine Purkinje strand preparations up to 148% (APD90) at 10 mumol/l. Concomitantly, OPC-8212 produced a 100% increase in developed force. Both prolongation of the action potential duration and the positive inotropic effect were readily reversed after exposure to tetrodotoxin, 3 mumol/l. Using Na-selective microelectrodes, intracellular Na+ ion activity increased 225% upon exposure to 10 mumol/l OPC-8212. OPC-8212 represents a novel type of positive inotropic agent, possessing both cAMP-dependent (selective PDE isozyme inhibition) and cAMP-independent (activation of intracellular Na+) mechanism of action.

Action Potentials↗

Evaluation of surgical staples for ligation of the renal pedicle during nephrectomy.

A mechanical stapling instrument was evaluated for ligation of the renal pedicle during nephrectomy in nine healthy sheep. Two forms of disposable loading unit, from which stainless steel surgical staples could be dispensed in double or triple staggered row configuration, were assessed for their proper function when applied across the renal pedicle singularly or in series. The response of the sheep to surgery was assessed by physical, hematological, and serum chemistry evaluations. Tissue healing was determined by gross and histopathological examinations. Ligation and transection of the pedicle took 2 to 4 minutes. The vessels of the pedicle ranged in diameter from 3 to 12 mm. In two sheep, overzealous stripping of perivascular tissue from the renal pedicle prior to placement of a triple staggered row of staples resulted in mild hemorrhage from the renal stump. This was controlled by placing a second triple staggered row of staples proximal to the first. It was concluded that ligation of the renal pedicle could be performed rapidly, effectively, and safely in healthy sheep using the correctly applied mechanical stapler. It is inferred that a similar technique would be applicable to other species including man.

Animals↗

Renal pathology in von Hippel-Lindau disease.

Von Hippel-Lindau disease, a rare autosomal disorder, is associated with multiple lesions, including a high incidence of renal lesions and CNS hemangioblastomas. Renal lesions have traditionally been classified as either benign cysts or solid renal cell carcinomas with or without cystic degeneration. We examined seven kidney specimens from four patients with von Hippel-Lindau disease. We found that renal cysts form a histopathologic continuum ranging from benign cysts (with one to two cell layers of bland epithelium), atypical cysts (demonstrating epithelial hyperplasia with or without mild cytologic atypia), to malignant cysts harboring renal cell carcinoma. The presence of atypia or foci of carcinoma does not correlate with cyst size. Lesions that appear radiologically or grossly solid range from conventional solid renal cell carcinoma, sometimes evidencing cystic degeneration, to lesions that are predominantly hyalinized, fibrotic nodules. In contrast to simple cysts occurring in the general population, which are virtually always benign, renal cysts in patients with von Hippel-Lindau disease may contain occult carcinoma. Radiologic evaluation, visual inspection at surgery, and even frozen section analysis of cyst lesions cannot be relied on to detect small foci of carcinoma. The spectrum of pathologic changes and the multicentricity of the renal lesions in von Hippel-Lindau disease complicate the radiologic evaluation and surgical management of these patients.

Adult↗

Usefulness of angioscopy in stenotic processes of the carotid--a comparison with morphological findings.

The development of a new generation of ultrathin flexible fiberscopes permitted direct in-vivo intravascular visualization of pathological changes. But not until the construction of a double-lumen balloon catheter for simultaneous obstruction of the blood flow and rinsing of the vessel did an accurate percutaneous transluminal examination become possible. For testing the usefulness of angioscopic intraluminal diagnosis, 48 carotid arteries from 32 autopsies were examined independently by angioscopy and morphologically. There was a high degree of correspondence between the two methods, especially in cases with low-degree stenosis or complicated plaques, in which other examination methods often fail. Problems of underestimating fibrous plaques and optical projection upstream of the stenosis are discussed.

Arterial Occlusive Diseases↗