Heat stress causes testicular germ cell apoptosis in adult mice.

An investigation was undertaken to determine whether the germ-cell loss associated with exposure of the testis to abdominal temperature occurs by apoptosis. Using an adult-mouse model of experimental unilateral cryptorchidism, it was observed that DNA fragmentation, consistent with apoptosis, was observed on day 6 in the cryptorchid testis, with subsequent loss of testicular weight, histologic evidence of germ-cell loss, and histochemical staining of apoptotic germ cells observed on day 7. Vacuolization of the germinal epithelium and the appearance of multinucleated giant cells was noted synchronously with the onset of germ-cell loss. Histochemical staining for apoptosis was noted most frequently among the primary spermatocytes and round spermatids. These results indicate that the testicular germ-cell loss observed with exposure to abdominal heat stress occurs by apoptosis. Further investigation of the biochemical mechanisms involved in testicular apoptosis may provide strategies to address a variety of male reproductive issues such as contraception and infertility.

Symptomatic fluid retention in patients on continuous peritoneal dialysis.

The clinical features, pathogenesis, management, prognosis, and predictors of symptomatic fluid gain (SFR) were analyzed for 71 episodes occurring in 66 patients on continuous peritoneal dialysis, 94.4% on continuous ambulatory peritoneal dialysis (CAPD) and 5.6% on continuous cycling peritoneal dialysis. Compared with a control group of 149 CAPD patients, the SFR group had a higher percentage of diabetics (64 versus 46%) and a higher frequency of noncompliance with fluid restriction (76 versus 22%), salt restriction (74 versus 23%), and performance of dialysis (30 versus 7%) (all at P < or = 0.015). Peripheral edema (100%), pulmonary congestion (80%), pleural effusions (76%), and systolic (83%) and diastolic (66%) hypertension were the most common manifestations of SFR. The annual hospitalization rate for SFR was 4.1 +/- 5.8 days per patient. SFR resulted in the discontinuation of CAPD in 10 patients and death in 1 patient. Serum sodium concentration was not different between dry and maximal weight in the SFR group. Thirty-eight (58%) of SFR and 61 (41%) of control patients were evaluated by peritoneal equilibration tests (PET). SFR patients had lower PET drain volume (2.08 +/- 0.47 versus 2.54 +/- 0.23 L) and a higher frequency of high peritoneal solute transport (32.2 versus 2.4%). In this group, logistic regression identified dietary noncompliance, low PET drain volume, and young age as independent predictors of SFR. Response to management and preventive measures was inconsistent. The best results were obtained by the use of short dwell exchanges with hypertonic dialysate in compliant patients with high peritoneal solute transport. SFR has serious consequences in CAPD. (ABSTRACT TRUNCATED AT 250 WORDS)

Inhibition of interleukin 1-induced biosynthesis of stromelysin by the calcium antagonist TMB-8 (8-(N, N-diethylamino)octyl-3,4,5-trimethoxybenzoate HCl).

This study was done to identify agents that can inhibit interleukin 1 (IL1)-induced stromelysin biosynthesis and to gain insight into the mechanism of IL1 action. For this purpose, various agents known to modulate calcium-dependent signal transduction pathway were evaluated in rabbit synovial fibroblast (RSF) cultures. Only the conditioned medium from RSF treated with the intracellular calcium antagonist TMB-8 (8-(N,N-diethylamino)-octyl 3,4,5-trimethoxybenzoate hydrochloride) had significantly lower proteoglycan-degrading metalloproteinase activity than controls. Biosynthetic labeling, immunoprecipitation and immunohistochemical studies, using a polyclonal antibody against rabbit stromelysin, demonstrated that TMB-8 inhibited synthesis stromelysin, the proteoglycan-degrading matrix metalloproteinase. Further evaluation of the TMB-8 effect revealed that the compound had no effect on secretion and that it was not acting by preventing activation of the proenzyme or by inhibiting the enzyme activity. These results suggest that TMB-8 may be inhibiting stromelysin synthesis by limiting intracellular calcium levels.

Subchronic toxicity of pentostatin in Wistar rats.

Pentostatin, an adenosine deaminase inhibitor, has been approved for the treatment of refractory hairy cell leukemia. In a preclinical toxicity study, Wistar rats were administered 0, 1, 10, 25, and 50 mg/kg (0, 6, 60, 150, and 300 mg/m2, respectively) pentostatin intravenously once a week for 26 wk (1.5-75-fold above the therapeutic dose in humans). Lymphoplasmacytic thyroiditis was present in 20% of females given 25 mg/kg and in 20 and 47% of males and females given 50 mg/kg, respectively. Thyroiditis was still present 4 wk following drug withdrawal. Thyroiditis was characterized by glandular enlargement, follicular epithelial hyperplasia and degeneration, colloid depletion, and interstitial infiltrates of lymphocytes and plasma cells. Drug-related changes in other tissues included lymphoid depletion of T-cell regions of thymus, spleen, and lymph nodes; bronchiolization of alveolar ducts with accumulation of mucus and foamy macrophages; testicular atrophy with sperm granulomas; dermoepidermal lymphocytic infiltrates with ulceration and alopecia; and hepatocytomegaly.

Insulin-secreting pancreatic (islet cell) carcinoma in a cat.

A functional, insulin-secreting pancreatic (islet cell) carcinoma was diagnosed in a 17-year-old male Siamese cat. Diagnosis was made on the basis of clinical signs (i.e., seizures and stupor) that resolved temporarily after correction of hypoglycemia with feeding or intravenous administration of glucose, the finding of an inappropriately increased serum insulin concentration in the face of hypoglycemia, and prolonged resolution of hypoglycemia after surgical removal of the tumor. Primary islet cell tumor of the pancreas was confirmed by biopsy. The cat died 18 months later, and necropsy revealed metastases to regional lymph nodes and liver. Specimens of the tumor and metastatic lesions both stained positively for insulin.

Granular basal cell tumor in a Wistar rat.

A granular cell variant of a cutaneous basal cell tumor in a Wistar rat is described. The tumor resembles the variant as described in man and dogs. The granular basal cells contain cytoplasmic PAS positive granules, and immunostained positively with HMW cytokeratins. Ultrastructurally, the cytoplasmic granules were secondary lysosomes.

Preclinical toxicological evaluation of fostriecin, a novel anticancer antibiotic, in rats.

Fostriecin, a novel anticancer antibiotic produced by Streptomyces pulveraecus, is believed to act via inhibition of topoisomerase II. Single-dose intravenous administration to rats at dose levels of 8.8 to 48 mg/kg resulted in lethality at dose levels of 35 mg/kg and higher. Major toxic effects were observed primarily at 17.5 mg/kg and higher, were reversible, and consisted of bone marrow hypocellularity, leukopenia, neutropenia, thrombocytopenia, and diffuse necrosis of various lymphoid tissues. The kidney was also identified as a target organ. Renal effects were observed primarily at 20 mg/kg, were reversible, and included increases in serum BUN, creatinine, and 24-hr glucose excretion. Twenty-four-hour excretion of Na+, K+ and urine osmolality were decreased postdosing at 10 and 20 mg/kg. Renal lesions, observed primarily at 20 mg/kg, consisted of vacuolization and necrosis of proximal and distal tubular epithelium at the corticomedullary junction extending into the medulla. Repeated daily intravenous administration of fostriecin for 5 days to rats at dose levels of 2.5 to 26.5 mg/kg resulted in death at 10 mg/kg and above and similar hematologic, bone marrow, lymphoid tissue, and renal changes as observed in the single-dose study. Hematological, bone marrow, lymphoid, and renal changes observed in rats were consistent with the cytotoxic mechanism of action of the compound.

Immunohistochemical localization of chromogranin A in normal tissues from laboratory animals.

To analyze the distribution of Chromogranin A in endocrine cells of various species of laboratory animals (dog, gerbil, guinea pig, hamster, monkey, mouse, and fetal, neonatal, and adult rats), normal tissues were stained immunohistochemically with polyclonal anti-bovine Chromogranin A antiserum (SP-1). Selected tissues (pituitary, adrenal, thyroid, parathyroid, pancreas, brain, peripheral nerve, stomach, small and large intestine, bone marrow, spleen, thymus, lymph node, and liver) from these species and from the rabbit were stained with two monoclonal anti-human Chromogranin A antibodies (LK2H10 and PHE5) to compare the immunoreactivities of the monoclonal antibodies and polyclonal antiserum. Staining with the polyclonal antiserum (SP-1) resulted in a broader spectrum of immunoreactivity but had more nonspecific background staining than either monoclonal antibody. Immunoreactivity and staining intensity with SP-1 varied between species, but most endocrine tissues (pituitary cells in the anterior and intermediate lobes, thyroid "C" cells, adrenal medulla, parathyroid, pancreatic islets, and enterochromaffin cells) from most species stained positively. In some species, pancreatic alpha cells stained more intensely, and two populations of adrenal medullary cells with different staining intensities were observed. Sciatic nerve (axonal area) was immunoreactive with monoclonal antibodies and/or the polyclonal antiserum in several species. The spectrum of immunoreactive tissues from fetal and neonatal rats increased with age. There was good cross-reactivity between species with SP-1, but not with either LK2H10 or PHE5. These results indicate that many endocrine cells with secretory granules in laboratory animals express Chromogranin A and that a polyclonal antiserum, such as SP-1, is more sensitive in detecting this protein in various species than monoclonal antibodies such as LK2H10 or PHE5.

Immunocytochemistry of normal pancreatic islets and spontaneous islet cell tumors in dogs.

Immunocytochemical studies of the distribution of glucagon, gastrin, insulin, and somatostatin in normal canine pancreatic islets and 20 canine islet cell tumors were done using the peroxidase-anti-peroxidase (PAP) technique. In the normal adult canine pancreas, islets typically consisted of clusters of 20-30 cells, but smaller foci and even individual cells were identified. Alpha cells (glucagon) were often peripherally located, beta cells (insulin) were centrally located and most numerous, and delta cells (somatostatin) were the least numerous and randomly located. Both juvenile and adult canine pancreases did not stain for gastrin. Of the 20 tumors examined, 18 had positive immunoreactivity for insulin, nine for glucagon, 14 for somatostatin, and one for gastrin. Two tumors were uninterpretable due to autolysis. Three tumors were pure insulinomas, but no pure somatostatinomas, glucagonomas, or gastrinomas were identified. Most tumors and metastases had mixed positive immunoreactivity; one neoplastic cell type predominated with lesser numbers of other cell types. Metastatic sites (liver and lymph node) stained for insulin and somatostatin, only. Foci of non-neoplastic islet cell tissue (nesidioblastosis), often located at the pancreatic-mesenteric junction, stained strongly positive for insulin, glucagon, and somatostatin but not for gastrin. The tumor staining pattern did not consistently correlate with tumor function, as determined by blood glucose and serum insulin assays. The PAP technique works well on paraffin-embedded, formalin-fixed tissue using rabbit or guinea pig antisera as the primary antibody. Staining occurred on sections of paraffin blocks stored for up to 7 years.

Bilateral salpingitis, hydrosalpinx and oophoritis in a mare.

Bilateral salpingitis, hydrosalpinx and oophoritis were diagnosed in a mare with concurrent lymphosarcoma. Salpingitis, hydrosalpinx and oophoritis are rare in the mare (1,2,3,5,8,9,11-13). Bilateral salpingitis is an important cause of infertility in all species and is most often due to ascending infection (3-5,10,11). The source of salpingitis in this mare probably was ascending infection from the uterus after parturition. The apparent infertility of the mare was attributed to debilitation from the lymphosarcoma and multiplicity of genital pathoses.

Severe respiratory disease in dairy cattle in New York State associated with bovine respiratory syncytial virus infection.

Severe respiratory disease associated with bovine respiratory syncytial virus (BRSV) infection has been identified in dairy cattle in New York State. The cases identified occurred in dairy calves and heifers. The disease was characterized in 4 animals by pathologic changes including interstitial pneumonia, necrotizing bronchiolitis with multinucleated syncytial epithelial cells and interstitial emphysema. BRSV antigen was demonstrated in lung samples or was isolated in tissue culture in all 4 cases. A retrospective survey of 6279 bovine diagnostic accessions between 1977 and 1982 revealed 66 cases of interstitial pneumonia, often with concurrent bronchiolitis. In this 5 year period, only 1 case in 1981 had interstitial pneumonia and bronchiolitis with pathologic features consistent with BRSV infection. It is concluded that pathogenic BRSV has entered New York State and that it is contributing to clinical respiratory disease in dairy cattle.

Craniopharyngioma in a dog.

Craniopharyngiomas are rare in dogs. A 3 cm suprasellar craniopharyngioma in a 13-month-old male mongrel dog is described. The mass consisted of multiple microcysts and solid areas with mesenchymal proliferation in areas of transition. Tumour cells were arranged in solid sheets or separated into islands by thick bands of collagen. Squamous differentiation of tumour cells with keratin formation and a focus of osseous metaplasia were present. Occasionally, tumour cells were arranged in rosettes. Cysts were lined by a single layer of cuboidal to low columnar epithelium and contained proteinaceous fluid with numerous cholesterol clefts. The diagnosis was based on age of occurrence, location and histological appearance.