Stimulation of adrenal chromaffin cell proliferation by hypercalcemia induced by intravenous infusion of calcium gluconate in rats.

Increased incidence of adrenal pheochromocytoma is frequently encountered in rat carcinogenicity studies. In some of the studies, the finding is judged to be due to a rat-specific mechanism of carcinogenesis caused by a disturbance of calcium homeostasis. However, direct evidence that the proliferation of chromaffin cells in the adrenal medulla is induced solely by hypercalcemia is not available.

Characterization of multinuclear hepatocytes induced in rats by mitemcinal (GM-611), an erythromycin derivative.

Mitemcinal is an erythromycin derivative with motilin agonistic action, developed as a gastrointestinal motor-activating agent. The characteristics of mitemcinal-induced multinuclear hepatocytes (MNHs, hepatocytes with three or more nuclei per cell) from detailed morphological observations together with the results of a study on the mechanisms of MNH formation by combining cytocentrifuge preparations with 5-bromo-2'-deoxyuridine cumulative labeling are reported. MNHs were observed only in rats in the high-dose groups of the subchronic study, with a higher incidence in females and reversibility after twenty-eight days of drug withdrawal, but not observed in dogs.

Differences in bone responses to recombinant human granulocyte colony-stimulating factor between mice and rats.

The authors previously demonstrated that high doses of recombinant human granulocyte colony-stimulating factor (rhG-CSF) induce bone changes characterized by accelerated osteoclastic bone resorption and osteogenesis due to intramembranous ossification in rats. As a basis for future analysis of the mechanisms of rhG-CSF-induced bone changes, the present study was undertaken to determine whether the bone changes observed in rats are also induced in mice. The experiment was conducted under the conditions that clearly induce bone changes in rats.

Effects of lysine-induced acute renal failure in dogs.

This study investigates the effects of lysine-induced acute renal failure. Female dogs received a lysine hydrochloride (lysine) of 4500 mg/kg/day (3.75 ml/kg/hr) for 3 consecutive days.

PTHrP and PTH/PTHrP receptor 1 expression in odontogenic cells of normal and HHM model rat incisors.

Parathyroid hormone related peptide (PTHrP) was discovered as a causative factor of humoral hypercalcemia of malignancy (HHM). We examined PTHrP and its receptor (PTHR1) expression patterns in odontogenic cells in normal and HHM model rat incisors. Nontreated nude rats serving as the normal control and HHM model rats produced by implantation of PTHrP-expressing tumor (LC-6) cells were prepared.

Histopathological study of time course changes in PTHrP-induced incisor lesions of rats.

Parathyroid hormone related peptide (PTHrP) was discovered as a causative factor of humoral hypercalcemia of malignancy (HHM). In the present study using HHM model rats, the time course of odontoblastic response to PTHrP and its relation to incisal fracture were elicited. Nude rats were implanted with PTHrP-expressing tumor (LC-6) cells, mandibular incisors were collected at several time points.

Histopathological study on the PTHrP-induced incisor lesions in rats.

Parathyroid hormone related peptide (PTHrP) was discovered as a causative factor of humoral hypercalcemia of malignancy (HHM). The present study elucidates the histopathological characters of incisor lesions in the HHM rat model. Nude rats were implanted with PTHrP-expressing tumor (LC-6) cells, maintained for 12 weeks, after which the mandibular incisors were collected.

Investigation of the mechanism of drug-induced autoimmune hemolytic anemia in cynomolgus monkeys elicited by a repeated-dose of a humanized monoclonal antibody drug.

We investigated the mechanism of hemolytic anemia detected in a repeated-dose toxicity study using cynomolgus monkeys that were treated with a humanized antibody drug. This drug was an IgG1 monoclonal antibody (MoAb) that binds to the human HM1.24 antigen named anti-HM1.

Combination of fixation using PLP fixative and embedding in paraffin by the AMeX method is useful for histochemical studies in assessment of immunotoxicity.

To establish a method for processing lymphoid organs suited to morphological, immunohistochemical and enzyme histochemical analyses for assessment of immunotoxicity, we examined a combination of fixation with periodate-lysine-paraformaldehyde (PLP) fixative and embedding in paraffin by the AMeX method (PLP-AMeX method). Spleen and thymus removed from monkeys and rats were fixed in PLP fixative for 6 hours at 4 degrees C. After fixation, specimens were processed and embedded in paraffin by the AMeX method.

Subtotal nephrectomy stimulates cyclooxygenase 2 expression and prostacyclin synthesis in the rat remnant kidney.

Background: Recently, two isoforms of cyclooxygenase (COX) have been identified, a constitutive form (COX-1) and a mitogen-inducible form (COX-2). Several studies have suggested that COX is activated in renal insufficiency, but little is known about the relationship between progression of renal insufficiency and the COX isoforms.

Methods: Five-sixths-nephrectomized (NX) rats were used.