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Abstract. Activation of the complement system of adrenalectomized rats with an injection of cobra venom factor (CVF) caused death of the rats within 2.5 h. Morphologically, this activation provoked distinct congestion of the gastric glandular mucosa and pulmonary leukostasis. Pretreatment of the animals with dexamethasone abolished the undesirable responses completely. Injection of CVF to intact rats produced only slight responses, but caused a marked increase in the serum levels of corticosterone. Dexamethasone was found to be replaced by promethazine (H₁-antihistamine) or dimethylsulphoxide (scavenger of hydroxyl radicals) but not by indomethacine, ibuprofen (cyclooxygenase inhibitors), deferoxamine mesylate (iron chelator) or imidazole (thromboxane synthetase inhibitor). These results suggest that glucocorticoids protect the animals from the adverse effects of excessive complement activation and that they act as an inhibitor of the production or action of histamine and toxic oxygen products induced by complement activation.

Abstract.

Adipocytes from streptozotocin-diabetic rats showed a markedly reduced lipolytic response to glucagon concomitant with a 90% or greater decrease in the number of glucagon receptors per cell. In contrast, β-adrenergic receptors assessed by [³H]dihydroalprenolol binding and lipolysis stimulated by isoproterenol, dibutyryl 3′5′-cyclic AMP and 3-isobutyl-1-methylxanthine were reduced by only 10–25% in diabetic rats compared with controls. Furthermore, quantitative analysis of the relationship between the amount of cell-bound glucagon and the hormone-stimulated lipolysis revealed that the function of the remaining 10% of glucagon receptors remained intact in cells from diabetic animals. These findings suggest that the lipolytic cascades, including β-adrenergic receptors, in adipocytes are not greatly impaired by diabetes, and therefore, the unresponsiveness of these cells to glucagon is mostly due to a marked reduction in the number of glucagon receptors, probably as a result of a down-regulation by postprandial hyperglucagonemia.

Abstract. In order to clarify the intracellular localization of salivary peptide P-C-like immunoreactivity in human pancreatic B-cells, an immunohistochemical study at electron microscopic levels was carried out by the protein A-gold technique using antisera against insulin and salivary peptide P-C. Both salivary peptide P-C-like immunoreactivity and insulin-like immunoreactivity were present only in the insulin secretory granules of the pancreatic B-cells. However, the former immunoreactivity was lacking in many insulin secretory granules of foetal pancreatic B-cells while the latter immunoreactivity was seen in all insulin secretory granules. Salivary peptide P-C-like immunoreactivity was not found in the other kinds of cells in the islets. In a previous immunohistochemical study at light microscopic level, salivary peptide P-C-like immunoreactivity appeared in a few pancreatic B-cells at about the 16th week of gestation, in an increasing number during gestation, and was seen in all pancreatic B-cells a few months after birth. The present finding together with the above results suggest that absence of salivary peptide P-C-like immunoreactivity in some foetal pancreatic B-cells may be due to the underdevelopment of salivary peptide P-C-like immunoreactivity in each insulin secretory granule. From the examination of cross-reactivity of antisera against salivary peptide P-C to other kinds of salivary peptides and salivary Protein C, and from the results of an indirect immunofluorescence technique using three kinds of antisera including antisera against salivary peptide P-C, salivary peptide P-B and salivary Protein C, it was thought that salivary peptide P-C-like immunoreactivity in human pancreatic B-cells belongs neither to salivary Protein C nor to salivary peptide P-B nor to salivary peptide P-E, but either to salivary peptide P-C itself or to an unknown substance which has common antigenic determinants with salivary peptide P-C, salivary peptide P-B and salivary Protein C. Salivary peptide P-C-like immunoreactivity was not found in the pancreatic B-cells of other mammals. Thus, although a new substance other than insulin is present in the insulin secretory granules of the human pancreatic B-cells, its pathophysiological function remains unclear.

Abstract. An indirect immunofluorescence technique using antisera aganist salivary peptide P-C and against salivary Protein C was carried out on the laryngeal, tracheal and bronchial glands to examine whether salivary peptide P-C-like immunoreactivity, recently demonstrated in the serous cells of the human salivary glands, was also present in those of laryngeal, tracheal and bronchial glands and to ascertain whether salivary peptide P-C is a fragment of salivary Protein C or not. Salivary peptide P-C-like immunoreactivity was present in the serous cells of the human laryngeal, tracheal and bronchial glands. Observation of serial sections immunostained with two kinds of antisera revealed that cells reacting with antisera against salivary peptide P-C were identical to those reacting with antisera against salivary Protein C pre-incubated with salivary peptide P-C. The finding implied that salivary peptide P-C and salivary Protein C, originally isolated from human saliva, were also present in the serous cells of tissues other than the salivary glands. Furthermore, analysis of the primary structure of salivary peptide P-C and salivary Protein C together with the present morphological finding suggests that salivary peptide P-C is a COOH-terminal fragment of salivary Protein C. Thus, salivary Protein C and salivary peptide P-C may play some role in the function of the serous cells of the salivary and laryngo-tracheobronchial glands.

Abstract. Antisera against proline rich peptide P-C, recently isolated from human whole saliva were raised in rabbits by injections of peptide P-C-BSA conjugates. Immunohistochemical study using the antisera was carried out on human salivary glands, gut and pancreas. The results showed that peptide P-C like immunoreactivity was present not only in the salivary glands but also in the pancreatic islets, though not in the gut. Furthermore, immunostaining of adjacent thin sections revealed that cells reacting with antisera against peptide P-C were identical to those reacting with insulin antisera. As the antisera against peptide P-C did not have any cross-reactivities to insulin, glucagon, somatostatin, pancreatic polypeptide, VIP and human C-peptide, the antisera were considered to recognize specifically either peptide P-C related antigen or peptide P-C itself in human pancreatic B-cells. A novel substance, peptide P-C like immunoreactivity, may be present in pancreatic B-cells independent of pro-insulin and insulin.

Morphological similarity between the salivary glands and the pancreas has been reported, and amylase, kallikrein and glucagon are present in both. These findings seem to suggest some functional relation between the pancreas and salivary glands. Detection of peptide P-C like immunoreactivity in the pancreas and salivary glands would be a additional support for this idea. Although it is suggested that peptide P-C like immunoreactivity in pancreatic B-cells may play some role in the function of B-cells, its exact pathophysiological role remains obscure.

Abstract. An immunohistochemical study using antisera against proline rich salivary peptide P-C and insulin, glucagon, somatostatin and pancreatic polypeptide antisera was carried out on the foetal pancreas at different stages and on the newborn infant's, infant's, child's and adult pancreas to examine the time at which salivary peptide P-C like immunoreactivity appeared in the human pancreas. Salivary peptide P-C like immunoreactive cells first appeared as a few scattered cells in the foetal pancreas after 16 weeks of gestation and gradually increased in numbers during gestation. The cells corresponded only to insulin immunoreactive cells in the foetal, newborn infant's, infant's, child's and adult pancreas. Only some of the insulin immunoreactive cells in the foetal pancreas contained salivary peptide P-C like immunoreactivity while the majority of those in the infant's pancreas and all those in the child's and adult pancreas did so. The findings, together with the fact that the full sequence of salivary peptide P-C is identical to the COOH-terminal 44 amino acid residues of Salivary Protein C, led to the possibility that peptide P-C like immunoreactivity in the human pancreatic B-cells was not a moiety of the precursor of insulin and pro-insulin, but a moiety of Salivary Protein C. It has been suggested that, in saliva, Salivary Protein C aids in maintenance of the calcium concentration. Based on the hypothesis that peptide P-C like immunoreactivity in the human pancreatic B-cells may play some role in insulin release through the maintenance of the calcium concentration, the present finding seems to explain the fact that the mechanism for insulin release in the foetal pancreas is immature in spite of sufficient biosynthesis of insulin.

Abstract. Salivary peptide P-C like immunoreactivity, originally isolated from human whole saliva has later been found in the human pancreatic B-cells. In the present work an indirect immunofluorescence technique using monoclonal antibodies against isolated salivary peptide P-C was applied to Bouin fixed pancreas and parotid glands to study the possible identity of the two substances. Positive P-C immunofluroescence was found in the serous cells of parotid glands but not in pancreatic B-cells, suggesting that pancreatic P-C substance is not salivary peptide P-C itself, but a substance sharing the common antigenic site with salivary peptide P-C. To examine this, an indirect immunofluorescence technique using polyclonal P-C antisera pre-absorbed with six kinds of synthetic fragments (1–22, 23–44, 23–29, 30–44, 30–38 and 38–44) of salivary peptide P-C was applied to the human pancreas. The result showed that pancreatic P-C substance was a substance which shares the common antigenic site with the 38–44 amino acid residue of salivary peptide P-C. Western blot analysis using extracts of human pancreata further showed that pancreatic P-C substance is not a precursor of insulin but a protein with molecular weight of 11 500 dalton, indicating the presence of a new protein in the insulin secretory granules of human pancreatic B-cells.