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C Juhlin

Publications and source records attributed to C Juhlin.

At least 73 records · Page 4Linked to original sources

Distribution of monoclonal antiparathyroid antibody E11 in mice grafted with human parathyroid adenoma and carcinoma.

One hundred six immunoincompetent mice grafted with human parathyroid adenoma or carcinoma were used to evaluate distribution of the murine monoclonal antibody E11, which recognizes a calcium sensor of high molecular weight on the parathyroid cell surface. The subcutaneous parathyroid grafts were infiltrated with murine fibrous tissue, which seemed to increase with the duration of transplantation and the size of inserted tissue pieces. Intraperitoneal injection of biotinylated or 125I-labeled E11 antibody indicated time- and dose-dependent antibody accumulation, as well as the presence of unoccupied binding sites in the transplanted parathyroid tissue. The iodinated intact immunoglobulin G and Fab fragment of the E11 antibody demonstrated low radioactivity in the lung, liver, spleen, kidney, and intestine for up to 14 days, except for the Fab fragment, which was rapidly accumulated and cleared from the kidney. The peak radioactivity ratio in the adenoma tissue versus blood averaged 2.8 for the intact antibody and 5.3 for the Fab fragment, whereas the corresponding values for the carcinoma tissue were 8.6 and 8.8, respectively. These ratios increased considerably, especially for the adenoma specimens, when weights of the excised grafts were adjusted for the calculated content of parathyroid tissue. The results support that the E11 antibody may localize even minute amounts of human parathyroid adenoma and carcinoma tissue.

Adenoma↗

500-Kilodalton calcium sensor regulating cytoplasmic Ca2+ in cytotrophoblast cells of human placenta.

Two monoclonal IgG antibodies E11 and G11, which react with parathyroid and kidney tubule cells, are in the present communication demonstrated to immunostain the surface of cytotrophoblast cells in human placenta. The G11 but not the E11 antibody has earlier been found to interfere with the sensing and gating of extracellular calcium in parathyroid cells. Microfluorometric measurement of the cytoplasmic calcium (Ca2+i) concentration was performed on suspended placental cells loaded with fura-2. The E11-positive placental cells displayed biphasic and parathyroid-like increases in Ca2+i in response to extracellular Ca2+. This increase was blocked by the G11 antibody and absent in the E11-negative placental cells. A sandwich enzyme-linked immunosorbent assay was constructed in which the G11 and E11 antibodies were shown to react with the same molecule. This calcium sensor was isolated and found to consist of a single, glycosylated polypeptide of approximately 500 kDa.

Antibodies, Monoclonal↗

Expression of platelet-derived growth factor beta-receptors on stromal tissue cells in human carcinoid tumors.

Carcinoid tumors of the midgut type are slowly growing neoplasms which often present clinically and histologically pronounced fibrosis around the tumors. Cryosections from 41 neuroendocrine tumors (31 midgut carcinoid tumors, 8 endocrine pancreatic carcinomas, 1 parathyroid carcinoma, and 1 pheochromocytoma) and 22 nonneuroendocrine carcinomas were examined for the presence of platelet-derived growth factor (PDGF) beta-receptor by immunohistochemistry using the monoclonal antibody PDGFR-B2. Twenty midgut carcinoid tumor tissues (66%) and 4 endocrine pancreatic carcinomas (50%) and the parathyroid carcinoma stained positively with the antibody. In contrast, only 2 nonneuroendocrine tumor tissues (10%) were stained, and the staining in these cases was weak. The immunoreaction in the carcinoid tumors was observed in connective tissue cells adjacent to tumor cell clusters but not in the tumor cells themselves. The degree of positive PDGF beta-receptor expression in the carcinoid tissues seems to correlate positively with the presence of macrophages as determined by the monoclonal antibody anti-Leu-M5, but not with other infiltrated lymphocytes identified with the monoclonal antibody anti-Leu-4, or with anti-HLA-DR antibodies. Stromal cells adjacent to tumor cells, including small capillaries, stained more strongly than the stromal cells which were distant from tumor cell clusters. Furthermore, carcinoid tumor metastases from lymph nodes as well as from liver showed stronger immunoreactivity in the stromal cells with the PDGF beta-receptor antibody than the corresponding primary tumors. Our data suggest that carcinoid tumor cells may directly or indirectly induce expression of PDGF beta-receptor on adjacent stromal cells in the tumor tissue, which may contribute to the fibrosis that is often seen around carcinoid tumors.

Aged↗

Interaction of monoclonal antiparathyroid antibody with Ca2+ agonistic actions of Mn2+ in normal human parathyroid cells.

Effects of the monoclonal antiparathyroid antibodies G11 and E11 on Mn2+ interaction with individual normal human parathyroid cells were studied. At 0.5mM Ca2+, 3mM Mn2+ induced a rapid transient increase in cytoplasmic Ca2+ [Ca2+i] followed by quenching of the fluorescence from the Ca2+ indicator fura-2 as Mn2+ entered into the cells. Whereas the antibody E11 had no effects, treatment with G11 abolished the Ca2+i transient and considerably delayed the entry of Mn2+. The results support the presence of a cation-sensitive receptor mechanism on parathyroid cells and indicate that the antibody G11 not only blocks the interaction between Ca2+ and this receptor mechanism but also that of Mn2+.

Antibodies, Monoclonal↗

Expression of a cell surface antigen with potential Ca2+-sensor/receptor function in rat placenta and uterus.

The reactivities of monoclonal anti-parathyroid antibodies identifying a cell surface 'calcium sensing' mechanism were investigated in the placenta and uterus of the pregnant rat. The rat placenta showed positively stained cells at the end of pregnancy. Staining was confined exclusively to the columnar epithelial cells lining the sinuses of Duval. In the uterus, positive staining of the epithelium lining the uterine lumen was obtained exclusively prior to and during implantation.

Animals↗

The anti-Leu4 (CD3) monoclonal antibody reacts with proximal tubular cells of the human kidney.

A recent observation that certain kidney tubular cells, especially those in the normal kidney, were positively stained with the anti-Leu4 monoclonal antibody (MoAb) led us to investigate systematically the reactivity of three different anti-CD3 MoAb with a panel of normal human kidneys. Using immunohistochemical and immunofluorescence staining techniques, the anti-Leu4 MoAb was found to react with proximal tubular cells in all eight examined kidneys, while no tubular-cell reactivity was observed with the OKT3 or DAKO-T3 MoAb. In each kidney, however, all three antibodies reacted with a similar number of occasionally encountered T cells. The G11 MoAb, which has been reported to react with a calcium receptor-associated molecule, and the anti-Leu4 MoAb showed almost identical patterns of tubular-cell reactivity. The observed co-distribution of Leu4-expressing structures with a putative Ca2+ sensor in the kidney and the fact that binding of anti-Leu4 to T cells induces Ca2+-mediated signal transduction, warrant further studies on a potential role of Leu4-expressing structures in Ca2+ regulation of proximal tubular cells.

Antibodies, Monoclonal↗

Immunohistochemical reactivity of monoclonal antibodies generated after immunization of mice with cells from a psoriatic lesion.

Monoclonal antibodies were produced by immunizing mice with dispersed epidermal cells from a psoriatic plaque. We obtained 128 growing hybridoma clones. The immunohistochemical reactivity of the antibodies produced by these hybridomas was primarily screened on sections of skin biopsies from psoriatic plaques. Supernatants with positive staining were then tested on other dermatoses and human organs. Six supernatants stained infiltrating dermal cells and the whole epidermis in psoriatic lesions, but showed no reaction with sections from normal skin, ichthyosis, or acutely inflamed skin. With these antibodies, positive staining was also seen in some areas of the normal-appearing skin of patients with increasingly active psoriasis as well as after treatment in recently clinically healed lesions. A different and more heterogenous staining of epidermis with no or fewer infiltrating cells was seen in longstanding inflammatory disorders such as chronic eczema, neurodermatitis, lichen planus, discoid lupus erythematosus and mycosis fungoides. Scattered staining with these antibodies was in addition seen on infiltrating macrophage-like cells present also in other organs than skin and in some of the organs also other types of cells were stained, such as neck mucosal cells of the stomach, parts of duodenal mucosal cells, certain secretory cells in parotid gland, lung bronchiole and Hassall's bodies on the thymus. The cross-reactivity of antibodies to psoriatic lesions with other organs is of interest, since psoriasis might involve various tissues. Our findings support the idea that there exist unique cell surface antigens in psoriatic skin which might help elicit an immune reaction and/or be targets for such local immune reactions.

Adult↗

Parathyroid histology and cytology with monoclonal antibodies recognizing a calcium sensor of parathyroid cells.

Two monoclonal antibodies reacting with surface structures on exclusively parathyroid cells and proximal kidney tubule cells were evaluated in the microscopic diagnosis of parathyroid disease. Immunostained cryosections of adenomatous and hyperplastic parathyroid glands from 30 hypercalcemic patients with primary or uremic hyperparathroidism (HPT) showed a reduced and heterogeneous staining with the antibodies. This contrasted with the intense and even staining of normal and suppressed human parathyroid glands, as well as lymph node metastases of parathyroid carcinoma. Fine-needle aspiration biopsies and imprints of the parathyroid glands showed a conspicuous antibody staining that enabled the identification of parathyroid cells. The antibodies seem to provide new means for histologic and cytologic identification of normal and pathologic parathyroid tissue, in conjunction with their highly restricted tissue reactivity. Because one of the antibodies interacts with a surface receptor mechanism of the parathyroid cells that is involved in the sensing and gating of calcium and, thereby, also with the regulation of parathyroid hormone release, the unequivocal demonstration of reduced staining of the adenomatous and hyperplastic parathyroid tissue suggests that HPT is associated with reduced expression of the calcium sensoring mechanism of the pathologic parathyroid tissue.

Adenoma↗

Modulation of the Ca2+-sensing function of parathyroid cells in vitro and in hyperparathyroidism.

When raising the extracellular Ca2+ concentration stepwise from 0.5 to 3.0 mM, bovine parathyroid cells reacted with initial transient and sustained elevations of the cytoplasmic Ca2+ concentration (Ca2+i), as well as more than 50% inhibition of parathyroid hormone (PTH) release. Human parathyroid adenoma cells and bovine cells cultured for 1 day or exposed to a low concentration of a monoclonal antiparathyroid antibody exhibited right-shifted dependencies of PTH release and Ca2+i on extracellular Ca2+ and reduced Ca2+i transients. The protein kinase C activator 12-O-tetradecanoylphorbol-13-acetate (TPA) further right-shifted the dose response relationship for Ca2+ regulated Ca2+i of the adenoma cells, whereas the protein kinase C inhibitor 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7) tended to normalize it, without affecting Ca2+i of normal bovine cells. In cells from an oxyphil adenoma and a parathyroid carcinoma as well as in bovine cells cultured 4 days or exposed to a high concentration of the antiparathyroid antibody, there were no Ca2+i transients, very small increases in steady-state Ca2+i and nonsuppressible PTH release. The results suggest that reduced availability of a putative Ca2+-receptor and increased protein kinase C activity may be important factors in the decreased Ca2+ sensitivity of abnormal parathyroid cells.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Hyperparathyroidism is associated with reduced expression of a parathyroid calcium receptor mechanism defined by monoclonal antiparathyroid antibodies.

Parathyroid tissue from patients with hyperparathyroidism (HPT) exhibited reduced immunohistochemical reactivity with monoclonal antiparathyroid antibodies, previously shown to stain intensely the surface of normal human parathyroid cells and to interfere with a receptor mechanism of these cells which is involved in the sensing and gating of Ca2+. Parathyroid hormone (PTH) release and cytoplasmic Ca2+ concentrations (Ca2+i) of dispersed cells from the pathological parathyroid glands had right-shifted dependencies on extracellular Ca2+, and exposure to the antibodies rendered both Ca2+i and PTH release almost completely insensitive to changes in ambient Ca2+. The results suggest that reduced expression of a parathyroid calcium receptor mechanism may be an important cause for the aberrant PTH release in HPT.

Adenoma↗

Monoclonal anti-parathyroid antibodies interfering with a Ca2+-sensor of human parathyroid cells.

Previous findings indicate that binding of Ca2+ to an external receptor is part of the mechanism by which extracellular Ca2+ regulates cytoplasmic Ca2+ and hormone release of parathyroid cells. We now present evidence that two newly generated monoclonal anti-parathyroid antibodies react with structures involved in this sensing and/or gating of Ca2+. Microfluorimetric studies of fura 2-loaded human parathyroid cells thus revealed that the antibodies competed with Ca2+ and antagonized the rise in cytoplasmic Ca2+ normally obtained when parathyroid cells are exposed to increasing concentrations of extracellular Ca2+.

Antibodies, Monoclonal↗

Improved myocardial protection by creatine phosphate in cardioplegic solution. An in vivo study in the pig during normothermic ischemia.

The effect of creatine phosphate in potassium cardioplegia was studied in a pig heart model in vivo. Fifteen pigs divided into two groups were placed on cardiopulmonary bypass and subjected to 1 hour of cardioplegic arrest at normothermia. In group I (control), in which a potassium cardioplegic solution was used, only two out of eight animals could successfully be weaned from bypass. In group II, on the other hand, in which creatine phosphate (10 mmol/l) was added to the cardioplegic solution, six out of seven animals could be weaned from bypass and the heart performance assessed by volume loading. Group II also exhibited better maintenance of high-energy phosphates during ischemia, with significantly higher adenylate charge potential, than group I. In all animals weaned from bypass--two in group I and six in group II--the ventricular performance was decreased compared with that before induction of ischemia. The results indicate that creatine phosphate could be an effective constituent in potassium cardioplegia.

Animals↗

Monoclonal antibodies with exclusive reactivity against parathyroid cells and tubule cells of the kidney.

Four monoclonal anti-parathyroid antibodies were generated after immunization of mice with intact cells from human parathyroid tissue. All four monoclonal antibodies reacted in immunohistochemistry with structures present on parathyroid epithelial cells and proximal-tubule cells of the kidney but were unreactive with all other human tissues investigated. Immunofluorescence microscopy on suspended human parathyroid cells showed that the antibodies reacted with structures present on the cell surface. Two of these antibodies efficiently blocked the increase in cytoplasmic calcium concentration of parathyroid cells that is normally associated with increased concentrations of extracellular calcium. The results indicate that these two antibodies interfere with a calcium-sensing mechanism of parathyroid cells--i.e., a potential calcium receptor by which extracellular calcium regulates cytoplasmic calcium and hormone release in these cells.

Animals↗

Functional effects of phosphoenolpyruvate and ATP on pig hearts in cardioplegia and during reperfusion. An in vivo study with cardiopulmonary bypass.

The effects of phosphoenolpyruvate (PEP) and ATP in cardioplegia and during early reperfusion were studied in pigs. Twenty pigs divided into three groups were placed on cardiopulmonary bypass and subjected to 2 h of hypothermic cardioplegic arrest. Group I (n = 7) served as a control. In group II (n = 7) PEP (14.4 mM) and ATP (0.067 mM) were added to the cardioplegic solution. Group III (n = 6) was given PEP (28.8 mM) and ATP (0.134 mM) with 500 ml of isotonic NaCl in the aortic root during early reperfusion. All animals in group III were weaned from bypass compared with 6 of 7 in group I and 5 of 7 in group II. Forty minutes after ischemia group III was assessed to be the only group with an unchanged aortic flow and stroke volume. The total peripheral resistance and arterial pressure were reduced in this group. The results demonstrate that PEP and ATP administered during reperfusion have a beneficial effect and that this may be exerted both on the myocardium and on the peripheral vessels.

Adenosine Triphosphate↗

MHC class I and II antigen expression and interferon alpha treatment of human midgut carcinoid tumors.

Cryosections of 28 primary and metastatic midgut carcinoid tumors from 12 patients with carcinoid syndrome were investigated immunohistochemically with antibodies that recognize human MHC class I (HLA-ABC) and class II (HLA-DR) antigens. The tumor parenchyma of all six patients treated with interferon alpha (IFN-alpha) during a mean 8.6 months (3 x 10(6) to 5 x 10(6) U three times weekly) exhibited unequivocal HLA-ABC immunoreactivity, with only minor discrepancies between primary lesions and metastases in mesenteric lymph nodes and liver. Class I staining was absent on the tumor cells of all 14 specimens from the patients without IFN therapy but was induced by culturing freshly dispersed tumor cells in vitro for 48 hours in the presence of recombinant IFN-alpha. The stroma of all neoplasms displayed class I and II immunostaining, as did usually a few CD4-expressing cells. The carcinoid specimens lacked parenchymal HLA-DR immunoreactivity, which is interesting considering suggestions on improved prognosis for bowel carcinomas lacking the class II expression. The study supports the idea that induction of MHC class I antigens could contribute to the beneficial clinical effect of IFN-alpha treatment in patients with midgut carcinoid tumors.

Aged↗