Studies on chicken polyclonal anti-peptide antibodies specific for parathyroid hormone-related protein (1-36).

Chicken polyclonal antibodies were prepared against a synthetic peptide corresponding to the first 36 N-terminal amino acids of parathyroid hormone-related protein (PTHrP) by immunizing laying hens. Significant increases of antibodies to PTHrP were first detected after the second immunization. Production of anti-PTHrP egg yolk antibodies peaked 1-2 weeks after the second through sixth immunizations and declined over a period of 2-4 weeks.

Mechanisms of cancer-induced hypercalcemia.

Cancer-associated hypercalcemia is due to the: (a) elaboration of systemically-acting humoral factors by neoplasms which alter calcium metabolism in bone, kidney, and intestine; or (b) stimulation of bone resorption at sites of tumor metastasis to bone. It is likely that both mechanisms occur in the same patient with certain neoplasms. There are many humoral factors that can be produced by tumors, secreted into the circulation, and have distant effects which induce hypercalcemia.

Effects of cyclosporin A on rat osteoblasts (ROS 17/2.8 cells) in vitro.

The effects of the immunosuppressive drug cyclosporin A (CsA) were evaluated on ROS 17/2.8 cells in vitro. ROS cells were treated with CsA (0, 0.

Polycystic kidney disease and renal lymphoma in a cat.

A 2-year-old castrated domestic shorthair cat was determined to have polycystic kidney disease (PKD) and renal lymphoma. History and examination findings consisted of progressive lethargy, asymmetric renomegaly, thick segments of small intestine, and anisocoria. Initial diagnostic tests revealed nonregenerative anemia, mild azotemia, and multiple, round anechoic cysts in both kidneys.

Parathyroid hormone (PTH)-related protein, PTH, and 1,25-dihydroxyvitamin D in dogs with cancer-associated hypercalcemia.

Circulating N-terminal PTH-related protein (PTHrP), N-terminal PTH, and 1,25-dihydroxyvitamin D [1,25-(OH)2D] concentrations were measured in normal dogs and dogs with cancer-associated hypercalcemia (CAH), parathyroid adenomas, and miscellaneous tumors. PTHrP was undetectable (less than 1.8 pM) in normal dogs and increased in dogs with CAH due to adenocarcinomas derived from apocrine glands of the anal sac (44.

Effects of humoral hypercalcemia of malignancy on the parathyroid gland in nude mice.

The ultrastructure of parathyroid chief cells was examined from four groups of nude mice (NIH:Swiss) with different serum calcium concentrations. The groups consisted of eight male mice with hypercalcemia induced by transplantable canine adenocarcinoma (CAC-8), eight female mice with hypercalcemia induced by infusion of parathyroid hormone-related protein, ten male control mice, and six male mice fed a low calcium (0.01%) diet.

Serum lipoprotein concentrations and hepatic lesions in obese cats undergoing weight loss.

Serum lipoprotein concentrations, routine serum biochemical values, and morphologic changes of the liver were evaluated in cats undergoing weight loss. Food was withheld from 6 obese and 6 control cats for 3 days (days 0 to 2), followed by feeding 50% of previous food intake for 26 days (days 3 to 28). Percutaneous liver biopsy specimens were obtained from all cats on days 0, 7, 14, and 28.

Transplantation of large granular lymphocyte leukemia in congenitally athymic rats.

Twenty-two congenitally athymic nude (rnu/rnu) rats were transplanted with large granular lymphocyte leukemia derived from F344 rats and then compared with ten similar rats inoculated with a suspension of normal F344 rat spleen cells. The normal spleen cells and tumor cells from a spontaneous, naturally occurring leukemia did not grow or cause clinical disease in any of the rats. All rats inoculated with a serially passaged leukemia cell inoculum had local growth at the inoculation site that spread widely and resulted in progressive tumor growth.

Effects of mithramycin on calcium metabolism and bone in dogs.

Mithramycin (0.1 mg/kg) was administered intravenously to eight Beagle dogs on days 0 and 7 to determine its effects on calcium and phosphorus metabolism, serum parathyroid hormone concentration, osteoclastic bone resorption, and serum biochemical and hematologic parameters. Ionized calcium concentration was paradoxically increased on day 1 and decreased on day 8 in association with an increased serum parathyroid hormone concentration.

Effects of 5-fluorouracil, leucovorin, and glucarate in rat colon-tumor explants.

In a previous study, we showed that 5-fluorouracil (FU) is active against the dimethylhydrazine-induced colon tumor in rats; a 7-day infusion of FU at 30 mg/kg daily produced 85% tumor-free cures. The present study examined the effects of FU alone and in combination with leucovorin (LV) or D-glucarate (GT) using an ex vivo system that maintained the growth of the rat colon-tumor explants on collagen gels. The labeling index (LI) was determined by the incorporation of [3H]-thymidine and autoradiography.

Parathyroid hormone-related protein binding to human T-cell lymphotropic virus type I-infected lymphocytes.

An HTLV-I-infected human lymphocyte line (MT-2) was evaluated for 1) the presence of receptors for PTH-related protein (PTHrP), 2) cell proliferation in response to PTHrP, and 3) adrenylate cyclase and intracellular calcium response to PTHrP. PTHrP-(1-36) was labeled with 125I, purified, and used to detect binding to MT-2 cells. Specific binding ranged between 4-9% of the total radioactivity.

Effects of transforming growth factor-alpha on parathyroid hormone- and parathyroid hormone-related protein-mediated bone resorption and adenylate cyclase stimulation in vitro.

The effects of transforming growth factor-alpha (TGF alpha) were determined on the ability of parathyroid hormone (PTH) or parathyroid hormone-related protein (PTHrP) to stimulate bone resorption and adenylate cyclase in vitro. Bovine PTH-(1-34) and human PTHrP-(1-34) were equipotent in their ability to stimulate bone resorption in neonatal mouse calvaria with maximal stimulation (2.9 and 2.

Effects of interleukin-1 alpha and cyclosporin A in vivo and in vitro on bone and lymphoid tissues in mice.

The purpose of this study was to investigate the effects of interleukin-1 alpha (IL-1 alpha) infusion and the ability of cyclosporin A (CYA) to alter IL-1 alpha-induced effects on bone in vivo and in vitro and lymphoid organs in vivo. Mice were administered: IL-1 alpha (2, 4, or 6 days), CYA (6 days), or IL-1 alpha and CYA (6 days). Hypercalcemia was induced in mice treated with IL-1 alpha compared to controls and CYA treated mice, and decreased urinary calcium excretion was present in IL-1 alpha and CYA groups.

Involvement of PGE synthesis in the effect of intermittent pressure and interleukin-1 beta on bone resorption.

Human periodontal ligament (PDL) fibroblasts, cultured from extracted healthy premolars, and a cloned osteogenic cell line (MC3T3-E1) were used in this study to determine the effect of intermittent pressure on bone resorption. Cells (1 x 10(5] were incubated with BGJb medium in the presence or absence of the following factors: intermittent negative (-30 g/cm2) or positive (30 g/cm2) hydrostatic pressure and interleukin-1 beta (IL-1 beta, 1 ng/mL), for 24 h. Conditioned media (CM) generated from cultures of either cell types were used for prostaglandin E (PGE) assay, bone resorption assay, and assessment of osteoclast (OC)-like cell formation.

Effect of etidronate disodium on the development of bone lesions in an animal model of bone metastasis using the human prostate cancer cell line PC-3.

We have established an animal model of bone metastasis using the PC-3 human prostate tumor cell line. In order to assess whether inhibition of bone resorption would prevent the development of bone metastasis, the diphosphonate etidronate (EHDP) was administered to 20 mice at a dose of 30 mg/kg subcutaneously daily starting 2 days prior to injection of tumor cells. Control mice received daily injections of the saline vehicle.

Effects of large granular lymphocyte leukemia on bone in F344 rats.

Large granular lymphocyte (LGL) leukemia was induced in 40 F344 rats by inoculating them with neoplastic cells to evaluate the effect of acute leukemia on bone remodeling and calcium balance. The rats developed leukemia and splenomegaly by 9 days after inoculation. The rats had reduced body weight (day 12), food intake (days 4, 8, 12), urine production (day 12), and fecal output (day 12).

Effects of progesterone on postovariectomy bone loss in aged rats.

The effects of progesterone on oophorectomy-induced bone loss in aged rats were evaluated. Female rats aged 12 months were divided into three groups: (1) sham-operated controls (SHAM); (2) oophorectomized (OVX); (3) OVX rats treated with progesterone (OVX + PROG). After 20 weeks the dry weight, bone ash, and calcium content of femur, tibia, and fourth lumbar vertebra were significantly lower in OVX than in sham rats.

Bone-resorbing activity and prostaglandin E produced by human periodontal ligament cells in vitro.

Human periodontal ligament (PDL) cells were derived from healthy premolars extracted for orthodontic treatment and were utilized for in vitro experiments in passages 4-6. Human PDL cells were seeded in tissue culture tubes and incubated with interleukin-1 alpha (IL-1 alpha), IL-1 beta, tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), indomethacin, parathyroid hormone (PTH), or their combinations, for 1 h. The medium was then replaced with serum-free BGJb medium and incubated for 24 h without further additions.

Tumor resection and antibodies to parathyroid hormone-related protein cause similar changes on bone histomorphometry in hypercalcemia of cancer.

Bone resorption is increased in both humoral hypercalcemia of malignancy (HHM) and primary hyperparathyroidism. On the other hand, bone formation parameters are increased in primary hyperparathyroidism and decreased in HHM. Recently, a PTH-related protein (PTHrP) has been shown to be responsible for the hypercalcemia in the syndrome of HHM.

Recurrent torsion of the spermatic cord and scrotal testis in a stallion.

A stallion was twice referred for evaluation of scrotal swelling and signs of pain. The first admission followed a 3-year period of recurrent signs of left-sided scrotal pain and swelling. After the removal of the left testis because of testicular torsion, the stallion was returned to service.

Identification of parathyroid hormone-related protein in canine apocrine adenocarcinoma of the anal sac.

The presence of parathyroid hormone-related protein (PTHrP) in the apocrine adenocarcinoma tumor line (CAC-8) derived from a hypercalcemic dog was demonstrated by western and northern blot analyses. Western blots of CAC-8 tumor extracts revealed a major protein with a molecular weight of approximately 18,000 daltons that cross-reacted with antiserum to human PTHrP. Northern blots demonstrated multiple-sized messenger RNA transcripts in CAC-8 that hybridized to a full-length cDNA probe to human PTHrP.

Histopathologic and gross effects of testicular biopsy in the dog.

Eighty-one mixed breed intact male dogs were divided into three groups: Group 1 = left testicle biopsied by Trucut needle method (n=36); Group 2 = left testicle biopsied by Incisional method (n = 39); Group 3 = not biopsied (n = 6). The dogs were castrated 1 to 36 d following biopsy. The biopsy specimens and both testicles were examined for gross and histologic lesions.

Caval syndrome in a Dirofilaria immitis-infected dog treated with dichlorvos.

In the dog of this report, lesions found were compatible with death attributable to acute circulatory collapse induced by caval syndrome and compounded by microfilarial death. Hepatic centrilobular hemorrhage and necrosis were suggestive of circulatory collapse, renal hemosiderosis was suggestive of disseminated intravascular coagulopathy, and multifocal subacute hepatic inflammation associated with microfilariae was similar to lesions attributed to microfilarial death. Treatment with dichlorvos may have precipitated these events.

Separation of parathyroid hormone-like activity from transforming growth factor-alpha and -beta in the canine adenocarcinoma (CAC-8) model of humoral hypercalcemia of malignancy.

A canine adenocarcinoma model (CAC-8) of humoral hypercalcemia of malignancy was evaluated for transforming growth factors (TGF)-alpha and -beta, PTH-like activity [adenylate cyclase-stimulating activity (ACSA)], and in vitro bone-resorbing activity. Biological activities present in CAC-8 were separated by reverse phase or cation exchange HPLC. TGF alpha in tumor extract was separated from TGF beta and ACSA by reverse phase HPLC.