The measurement of renal injury.

The classical assessment of nephrotoxicity by the measurement of serum urea nitrogen and creatine is insensitive and nonspecific. Selection from a battery of clinical pathology tests allows the sensitive and specific measurement of renal dysfunction and injury. This requires the collection of urine specimens of good technical quality, with appropriate preservation. Interaction of the test article with urinary enzymes should be evaluated prior to their measurement for the assessment of tubular injury. This enables the localization and quantification of the injury within the regions of the nephron. High resolution proton nuclear magnetic resonance spectroscopy, a technique for measurement of low molecular weight metabolites, shows great promise for the evaluation of renal tubular injury in toxicologic studies.

The effect of erythritol on the stability of gamma-glutamyl transpeptidase and N-acetyl glucosaminidase in human urine.

In toxicology studies and clinical trials of erythritol, treated animals and human subjects had higher urine gamma-glutamyl transpeptidase [gamma-glutamyl transferase (gamma-GT)] than untreated controls. It has previously been reported that gamma-GT activity in frozen urine decreases with time; therefore, a study was undertaken to examine the effects of storage temperature, time, and the presence of erythritol on the stability of gamma-GT and N-acetyl glucosaminidase in human urine. In this study, it was found that the rate of decrease of the activity of gamma-GT is much greater at -20 degrees C than at -70 degrees C. Variation in the storage temperature of the frozen urine is particularly deleterious to gamma-GT. The addition of erythritol in a concentration of 5% reduces this decrease. Approximately 15% of N-acetyl glucosaminidase activity is lost in the initial process of freezing the urine. Thereafter, conditions of temperature, time, and the presence or absence of erythritol account for little additional loss of activity.

How does service drive the service company?

"How Does Service Drive the Service Company?" presents commentators on Leonard A. Schlesinger and James L. Heskett's September-October article. Commentators include Michael R. Quinlan, Ron Zemke, Jim Snider, Dinah Nemeroff, Steven S. Reinemund, Robert Ayling, Karmjit Singh, James A. Perkins, Joseph E. Antonini, and Walter F. Loeb.

Effects of three methods of restraint an in rhesus and african green monkeys intravenous glucose tolerance testing.

The intravenous administration of 0.75 gm glucose per kg and the measurement of serum glucose pretest and at 10, 20, 30, 60, 90 and 120 minutes constitute a satisfactory protocol for intravenous glucose tolerance testing of Rhesus (Macaca mulatto) and African Green (Cercopithecus aethiops) monkeys. No significant differences were noted between animals restrained with ketamine hydrochloride and those restrained with sodium pentobarbital, but the African Green males and females and the male Rhesus monkeys yielded significantly different results while being manually restrained.

A coagulopathy of the owl monkey (Aotus trivirgatus) associated with high antithrombin III activity.

The species-associated coagulopathy of the owl monkey (Aotus trivirgatus) was shown to be caused by a high level of circulating anticoagulant, antithrombin III, in approximately 4-6 times the activity in which the same anticoagulant is found in man or the rhesus monkey (Macaca mulatta). The survival of the owl monkey in the presence of this added biological risk is an interesting and enigmatic observation. Treatment with protamine, prednisone, or estradiol did not alter the activity of circulating anticoagulant.

Characterization of a spontaneous undifferentiated carcinoma from an African green monkey (Cercopithecus aethiops).

An adult male African green monkey (Cercopithecus aethiops) with an undifferentiated carcinoma, probably originating from the nasal mucosa, was received from the Akron, Ohio zoo. Cultivation of this tumor in vitro resulted in a mixture of fibroblastic and epithelial cells which was subsequently separated using differential trypsinization. The neoplastic nature of the cultured epithelial cells was verified by their ability to transplant into athymic nude, or antithymocyte serum-treated mice, where poorly differentiated carcinomas were produced, and cultures of the tumors that arose in nude mice were morphologically similar to pretransplantation cultures. Early cultures showed a normal male karyotype characteristic of the species; however, in long-term cultures, a clearly defined, small submetacentric Y chromosome was not observed. Electron microscopic examination of tumor tissue and cultured tumor cells revealed desmosomes and the presence of cytoplasmic (keratin-type) fibrils, which tended to be organized around the nucleus. In addition to the keratin-type fibrils, the cultured tumor cells also contained a large amount of cytoplasmic inclusion material that may represent keratohyalin granules. There was no evidence of a viral association with tumor material or cultured cells. The cultures were susceptible to infection by vesicular stomatitis virus, Herpesvirus hominis type 1, and H. saimiri, but were resistant to the Epstein-Barr virus.

Chronic Herpesvirus saimiri infection in an owl monkey.

An adult owl monkey (Aotus tricirgatus) used for immunologic studies of Herpesvirus saimiri (HVS) developed early, late, membrane, and neutralizing antibodies to HVS approximately 3 weeks after the beginning of the experiment. HVS was isolated by the cocultivation of peripheral blood for over 1 year. No clinical, gross, or histopathologic findings of malignancy were exhibited by the animal. The HVS isolate from the animal was indistinguishable biologically and serologically from the original HVS strain of Meléndez and from an isolate of an experimentally HVS-induced tumor. Inoculation of this isolate into 2 young white-lipped marmosets (Saguinus fuscicollis) produced typical malignant lymphoma and lymphocytic leukemia. Our findings suggested that the virus from the chronically infected animal was oncogenic and that host factors were primarily responsible for determining the disease manifestation of the virus infection. Another owl monkey chronically infected with HVS for over 2 years has remained asymptomatic.

Responses of infant rhesus monkeys to inoculation with Mason-Pfizer monkey virus materials.

Rhesus monkeys neonatally inoculated with Mason-Pfizer monkey virus (M-PMV) and virus-infected cells frequently developed viral and/or bacterial pneumonia and enteritis. Three characteristic hematologic patterns occurred among the inoculated animals and correlated well with the probability of survival. Postmortem examination of the animals revealed lymphadenopathy and thymic atrophy. M-PMV was present in lymph nodes, blood, brain, spleen, thymus, kidneys, and bone marrow. The disease induced in some animals had characteristics suggestive of a slow-virus-induced autoimmune response.

Spontaneous lymphoma associated with Herpesvirus saimiri in owl monkeys.

Two cases of lymphoma and one case of lymphoproliferative disease were found in a group of 7 owl monkeys imported into our colony as a single group. Herpesvirus saimiri (HVS) was isolated from the tumor cells of 1 lymphoma by cocultivation and from kidney cell cultures from the monkey with lymphoproliferative disease. Antibody to HVS was found in serum samples from 2 monkeys positive for HVS but not in the sera from the 4 clinically normal monkeys. Antibody to Epstein-Barr virus-infected cells was also found in the serum from the animal with lymphoma.

Fibrous plaques in the aortas of adult female rhesus monkeys (Macaca mulatta).

Lesions in the abdominal aorta were found in 36 of 40 mature female rhesus monkeys given various oral contraceptive steroids and in 8 of 10 monkeys of a non-treated control group. The lesions consisted of proliferation of subendothelial smooth muscle cells and collagen, often with fragmentation of the internal elastic lamina, forming a plaque. These occurred also, in order of descending frequency, in thoracic aorta, aortic arch, femoral and iliac arteries, and the carotid and pulmonary arteries. They appear statistically unrelated to steroid treatment and lack correlation with body weight and blood cholesterol levels.

PIP: The effects of oral contraceptive (OC) steroids on fibrous plaques in the aorta were studied in 50 adult female rhesus monkeys. Mestranol with or without norethindrone was administered in 1 or 10 times the human dose cyclically for 7 menstrual cycles. Blood was obtained throughout the study for cholesterol determinations and the animals were sacrificed at the end of 7 cycles for gross and microscopic tissue examinations. 36 of 40 monkeys given OCs and 8 of 10 controls revealed lesions in the abdominal aorta. Proliferation of subendothelial smooth muscle cells and collagen, often with fragmentation of internal elastic lamina, forming a plaque, was revealed in the lesions. The lesions also occurred in descending frequency in thoracic aorta, aortic arch, femoral and iliac arteries and the carotid and pulmonary arteries. There was a tendency for serum cholesterol to increase with body weight but the lesions appeared to be unrelated to steroid treatment and appeared to lack correlation with body weight and cholesterol levels.