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C Limas

Publications and source records attributed to C Limas.

At least 55 records · Page 3Linked to original sources
PubMed1990

Influence of anti-beta-receptor antibodies on cardiac adenylate cyclase in patients with idiopathic dilated cardiomyopathy.

Autoantibodies against the cardiac beta 1-adrenoceptor are present in the sera of patients with idiopathic dilated cardiomyopathy and may modulate the responsiveness of cardiac beta-adrenergic pathways to agonists. The regulation of cardiac adenylate cyclase activity by autoantibodies was examined in 50 patients with dilated cardiomyopathy. Inhibition of isoproterenol-sensitive adenylate cyclase activity could be demonstrated by serum dilutions or IgG in 52% (26 of 50) of the patients; basal and NaF-stimulated activities, in contrast, were unaffected. In 14 patients, both ligand binding to beta-receptor and isoproterenol-sensitive adenylate cyclase activity were inhibited by 100-fold serum dilutions. Pretreatment of cardiac membranes with pertussis toxin did not affect inhibition of adenylate cyclase indicating that the effect of sera does not depend on Gi. The immunogenetic control of antireceptor antibodies was examined by comparing the distribution of HLA antigens in antibody-positive and antibody-negative patients. HLA-DR4 and HLA-DR1 were strongly associated with antibodies inhibiting ligand binding and adenylate cyclase activity (71% of patients with such antibodies typed as either DR4 or DR1). Conversely 58% of patients with HLA-DR4 and 71% of patients with HLA-DR1 antibodies showed inhibition of adenylate cyclase activity compared to 46% of those who lacked both HLA-DR4 and HLA-DR1 antibodies. These results strongly suggest that cardiac beta-adrenergic receptors and adenylate cyclase activity in dilated cardiomyopathy can be modulated by circulating autoantibodies, the presence of which is under the control of the major histocompatibility complex.

Adenylyl Cyclase Inhibitors↗
PubMed1990

Effects of xamoterol on the reversible cycling of cardiac beta-adrenoceptors.

We have examined the effects of xamoterol, a partial beta 1-adrenoceptor agonist, on cardiac beta-adrenoceptors using isolated myocytes and cell-free preparations. Xamoterol was considerably less effective than isoproterenol in stimulating adenylate cyclase activity but the difference was narrowed by 1 microM forskolin, presumably by inducing more efficient coupling to the catalytic subunit of the enzyme. Xamoterol mediated a time- and concentration-dependent loss of beta-adrenoceptors from the cell surface of cardiac myocytes through a process of internalization sensitive to the cytoskeleton inhibitors, colchicine and cytochalasine. In cell-free preparations, loss of membrane-bound beta-adrenoceptors induced by xamoterol, but not that induced by 1 microM isoproterenol, was prevented by the inhibitor of protein kinase A. In contrast, 100 nM heparin (an inhibitor of beta-receptor kinase) prevented the isoproterenol-but not the xamoterol-mediated decline of beta-receptors. In addition, 1 microM xamoterol attenuated the isoproterenol-mediated internalization of beta-adrenoceptors in cardiac myocytes over a wide range of isoproterenol concentrations. This attenuation required activation of protein kinase A. These results suggest that the influence of xamoterol on the cycling of cardiac beta-adrenoceptors involves different pathways than those utilized by isoproterenol.

Adenylyl Cyclases↗
PubMed1990

A,B blood group antigens in tissues of AB heterozygotes. Emphasis on normal and neoplastic urothelium.

The tissue distribution of the A and B blood group antigens was studied in 41 individuals with the heterozygous AB red blood cell (RBC) phenotype. A total of 134 biopsies from a variety of normal tissues (94 from urothelium and 40 from other tissues) were examined. In addition, changes in the expression of these antigens associated with neoplastic transformation were evaluated in 70 biopsies from transitional cell carcinomas of 19 AB heterozygous patients. There was heterogeneity in the distribution of tissue A and B antigens, depending on the cell type, as well as among cells of the same type. Ninety-one percent of AB heterozygotes expressed both A and B antigens in normal epithelial cells, with a mosaic distribution clearly apparent in 50% of these individuals. In 21% of these subjects, the A antigen was undetectable in the vascular endothelial cells in all biopsies from several organs. In most (79%) transitional cell neoplasms, only one of the two antigens was consistently expressed. The results of this study may have implications for the clonal or specific gene deletion theories of neoplasia. They also demonstrate the existence of a subgroup of AB individuals in whom the A antigen is absent specifically from the vascular endothelium.

ABO Blood-Group System↗
PubMed1989

Cytosolic factor(s) determines the impaired desensitization of beta-adrenoceptors in the myocardium of spontaneously hypertensive rats.

Loss of membrane-bound beta-receptors in the myocardium of spontaneously hypertensive rats has been explained on the basis of enhanced agonist-induced desensitization. However, in both cardiac myocytes and cell-free preparations, isoproterenol and cyclic AMP-dependent protein kinase are less effective in desensitizing beta-receptors from hypertensive compared to normotensive animals. Reconstitution of cardiac membrances from hypertensive rats with cytosol from normotensive controls restores the ability of isoproterenol and protein kinase A to desensitize beta-receptors. Impaired desensitization in spontaneously hypertensive rats is, therefore, not due to intrinsic defects of the beta-receptor but, rather, to absence of regulatory cytosolic factor(s).

Animals↗
PubMed1989

Localization of cathepsin B in normal and hyperplastic human prostate by immunoperoxidase and protein A-gold techniques.

Cathepsin B, a lysosomal cysteine protease, was localized in normal prostate and benign prostatic hyperplasia (BPH) using immunoperoxidase and protein A-gold techniques. Our objective was to determine whether cathepsin B was involved in the prostatic epithelium affected by nodular hyperplasia. All samples were collected immediately after prostatectomy. Immunohistochemical studies showed that the enzyme was expressed in the supranuclear cytoplasm of columnar cells and in numerous basal cells of normal and BPH acini. The strongest localization of cathepsin B occurred in acinar basal cells; hence, it is possible that cathepsin B could be useful as a marker for such cellular elements. Stromal macrophages showed reaction products, but lymphocytes and neutrophils did not. In both normal and hyperplastic glands, the enzyme was localized by gold particles in lysosomes, secretory granules, and vacuoles of columnar epithelial acinar cells. Immunoelectron microscopic study also showed the presence of cathepsin B in the heterochromatin (condensed chromatin) and nuclear membranes of columnar and basal cells, but not in euchromatin or nucleoli. At present, the function of cathepsin B in the nuclei of basal and columnar cells remains unknown. However, the cathepsin B in the cytoplasmic compartment might be associated with the lysosomal function of the cells. The role of cathepsin B as a marker for basal cell participation in the development of prostatic lesions should be studied further.

Cathepsin B↗
PubMed1989

Intracellular distribution of adrenoceptors in the failing human myocardium.

Although it is increasingly recognized that the density of cardiac membrane-bound beta adrenoceptors declines in heart failure, the mechanisms involved are unclear. Furthermore, it is not known whether cardiac alpha-1 adrenoceptors are similarly affected. Inasmuch as agonist-induced desensitization results in translocation of adrenoceptors from the plasma membrane to an intracellular vesicular fraction, we determined the intracellular distribution of cardiac adrenoceptors in two groups: group 1 (n = 9) consisted of papillary muscles from patients with mild-to-moderate heart failure undergoing valve replacement, and group 2 (n = 8) consisted of severely failing hearts removed during orthotopic cardiac transplantation. The density of cardiac beta adrenoceptors was lower in membranes from group 2 (17.8 +/- 3.3 fmol/mg protein vs 27.8 +/- 3.7 fmol/mg in group 1; (p less than 0.01), and the percentage of beta receptors recovered in the vesicular fraction was higher in group 2 (47.1 +/- 3.3% vs 36.8 +/- 5.0% in group 1; p less than 0.01). In group 1 but not group 2 there was a significant inverse correlation (r = -0.87; p less than 0.001) between the density of membrane-bound beta receptors and the percentage of beta receptors recovered in the vesicular fraction. Alpha-1 adrenoceptors were lower in both membrane and vesicular fraction of group 2 compared to group 1; in group 2 but not group 1 there was a significant negative correlation between the density of membrane-bound alpha-1 adrenoceptors and the percentage of alpha-1 receptors in the vesicular fraction (r = -0.8; p less than 0.01). These results suggest that the regulation of alpha-1 and beta adrenoceptors differs in the failing myocardium. Furthermore, agonist-induced desensitization may play a predominant role only in mild-to-moderate heart failure.

Cardiac Output↗
PubMed1989

HLA antigens in idiopathic dilated cardiomyopathy.

Disturbances of humoral and cellular immunity are common in patients with idiopathic dilated cardiomyopathy and they may contribute to the initiation and maintenance of myocardial damage. HLA antigens were studied in 102 patients with dilated cardiomyopathy and a control hospital population. HLA-DR4 was significantly more common in patients with idiopathic cardiomyopathy (41 patients, 40%) than in the control group (123 patients, 24%). The distribution of other antigens was not significantly different in the two groups. The distribution of blood group antigens, immunoglobulin concentrations, and disease severity was similar in patients with the HLA-DR4 antigen and those without it. These results suggest that HLA-DR4 antigen may be a genetic marker for susceptibility to dilated cardiomyopathy.

Adolescent↗
PubMed1989

Autoantibodies against beta-adrenoceptors in human idiopathic dilated cardiomyopathy.

Although it is recognized that the number of cardiac beta-adrenoceptors is reduced in human dilated cardiomyopathy, the mechanisms involved have not been defined. We examined the possible role of altered humoral immunity by comparing the effect of sera from patients with idiopathic dilated cardiomyopathy (n = 20), ischemic or valvular heart disease (n = 28), or controls with no known cardiac disease (n = 18) on the binding of radioligands to cardiac beta-receptors. The ability of sera from cardiomyopathic patients to inhibit the binding of [3H]dihydroalprenolol to rat cardiac membranes was significantly higher than that of the other two patient groups (40 +/- 5% at 50-fold serum dilution compared to 14 +/- 3% for the ischemic/valvular heart disease group, and 14 +/- 4% for the normal control group, p less than 0.001). A similar inhibition was exerted by IgG from cardiomyopathic patients. Only the number, not the affinity, of the beta-receptors was decreased by cardiomyopathic sera. This decrease could be prevented by preincubating the sera with anti-human IgG, indicating the presence of autoantibodies. Furthermore, the sera were ineffective against cardiac alpha 1-adrenoceptors and considerably less effective against lung beta 2-receptors. In addition to ligand binding inhibition, sera from cardiomyopathic patients could immunoprecipitate beta-adrenoceptors quantitatively from solubilized cardiac membranes. Positive sera inhibited significantly isoproterenol-stimulated adenylate cyclase with no effect on basal or NaF-stimulated activities. These results document the presence in sera from patients with idiopathic dilated cardiomyopathy of autoantibodies directed against the cardiac beta 1-adrenoceptor which may play an important role in the regulation of inotropic responsiveness to beta-agonists.

Adenylyl Cyclases↗
PubMed1988

Monoclonal antibody-targeted radiotherapy of renal cell carcinoma using a nude mouse model.

Radiation dosimetry and monoclonal antibody (MAB)-targeted radiotherapy studies were performed to evaluate the feasibility of using tumor-preferential MAB as targeting agents for internal radiotherapy of renal cell carcinoma (RCC). Two human RCC xenograft lines, TK-177G and TK-82, were established in nude mice and studied using MAB A6H as a targeting agent. This MAB has previously demonstrated excellent in vivo localization to RCC xenografts. Two doses of A6H (13 to 19 micrograms) labeled with iodine 131 (110 to 130 microCi) caused the tumor to regress or arrested the tumor growth in both xenografts. Similar doses (18 to 43 micrograms; 120 microCi) of 131I-labeled control MAB AFP-22 or of unlabeled A6H did not inhibit tumor growth. While most mice in the control groups had tumors greater than 250 mg in weight by day 43, none of the tumors in mice treated with 131I-labeled A6H grew to that size during the 3-month observation period. Sequential computerized scintigraphy was used to calculate the amount of radioisotope localized in tumor versus normal mouse tissue. Therapeutic doses of 131I-labeled A6H delivered a median calculated radiation dose of 38 cGy/microCi (range, 28 to 57) injected dose to RCC xenografts, and a median of 0.9 cGy/microCi to normal mouse tissues. These findings suggest that A6H is able to target radioisotopes highly specifically to RCC and achieve a therapeutic effect in the experimental setting.

Animals↗
PubMed1988

Primary malignant melanoma of the rectum. Evidence for origination from rectal mucosal melanocytes.

Reports of rectal melanoma often attribute the lesion to tumor extension from anal melanocytes which have undergone malignant transformation while the existence of true primary melanoma of the rectum has been disputed. This dispute primarily relates to past inability to demonstrate normal melanocytes in rectal mucosa. In this case report, two polypoid melanomas clearly located in the rectum were discovered at sigmoidoscopy. Thorough histologic examination failed to demonstrate atypical anal melanocytes, and the presence of normal melanocytes in the rectal mucosa was confirmed by electron microscopy and immunohistochemistry. Although rare, it appears that primary malignant melanoma may arise from melanocytes among columnar rectal epithelium.

Aged↗
PubMed1988

Impaired desensitization of cardiac beta-adrenoceptors in the spontaneously hypertensive rat.

Reduced inotropic responsiveness by spontaneously hypertensive rats (SHR) to beta agonists is associated with, and may be secondary to, a decline in cardiac membrane-bound beta adrenoceptors. It is widely assumed that this decline reflects a desensitization of the receptor secondary to enhanced sympathetic drive, but direct evidence is lacking. We examined this issue in cell-free cardiac preparations from age-matched SHR and Wistar-Kyoto (WKY) rats. Isoproterenol induced a time- and concentration-dependent decline in membrane-bound beta receptors but was considerably more effective in WKY than in SHR (43% decline versus 29% in SHR, P less than 0.01). Since cyclic AMP-protein kinase inhibitor prevented only 15-20% of the isoproterenol-induced decline, this was probably mediated by the beta receptor kinase. Cyclic AMP-dependent protein kinase induced a 38% desensitization in WKY rats but was completely ineffective in SHR. These results suggest that desensitization of the beta receptor is impaired in SHR, probably because the structural organization of the receptor in the cardiac membranes is altered.

Animals↗
PubMed1987

Homologous regulation of prostaglandin E2 receptors in rat renal medulla.

Prostaglandin (PG) receptors are present on enzymatically dissociated cells from the rat renal medulla and are subject to homologous regulation both in vivo and in vitro. One hour after injection of 100 micrograms of 16,16'-dimethyl-PGE2, the number of PGE2 binding sites on renal cells declines to 40% of controls. In vitro exposure of renal cells to PGE2 or dimethyl-PGE2 also results in a time- and concentration-dependent "down" regulation of prostaglandin receptors. In the absence of indomethacin in the incubation medium, endogenously synthesized prostaglandins mediate a similar time-dependent loss of cell-associated receptors. This loss is reversible since, after agonist removal and reincubation of the cells at 37 degrees C, there is a rapid (within 15 min) reappearance of PGE2 receptors (to 60-93% of controls). Reappearance occurs whether down regulation is induced in vitro by endogenously synthesized prostaglandins, added PGE2 or dimethyl-PGE2, or in vivo after injection of dimethyl-PGE2. Cycloheximide does not affect down regulation but significantly prevents subsequent recovery of the receptors. In contrast, neither colchicine nor chloroquine influences homologous regulation of renal prostaglandin receptors. These results document an agonist-induced reversible cycling of renal prostaglandin receptors which may determine the effectiveness of prostaglandin action in normal and pathologic states.

Animals↗
PubMed1987

Characterization of two human cell lines (TK-10, TK-164) of renal cell cancer.

Two previously unreported cell lines of human renal cell carcinoma are presented. TK-10 and TK-164 have each been in culture for over 4 years. The epithelial nature of both cell lines has been documented by light and electron microscopy. The cells in each line contain a Y chromosome, have specific marker chromosomes, and a distinct flow cytometric histogram. Both lines grow in agar, albeit not in athymic mice.

Adult↗