Herpesvirus type 2 isolated from cervical tumor cells grown in tissue culture.

A herpesvirus has been isolated from spontaneously degenerating cultures of cervical tumor cells grown in vitro. The virus was identified as a type 2 herpesvirus on the basis of biologic properties, including plaque morphology and microtubule formation in infected HEp-2 cells, and of immunologic specificity as determined by neutralization. Herpesvirus antigens and virus particles were not seen in duplicate cultures of viable cervical tumor cells.

Comparison of spontaneous and experimentally induced canine prostatic hyperplasia.

Spontaneous prostatic hyperplasia in the beagle appears to progress with age from a glandular to a cystic histological appearance. Prostatic hyperplasia can be induced in young beagles with intact testes by treatment for 4 mo with either dihydrotestosterone or 5 alpha-androstane-3 alpha, 17 beta-diol, alone, or with either of these steroids in combination with 17 beta-estradiol. In contrast, the induction of prostatic hyperplasia in young castrated beagles, in which the gland had been allowed to involute for 1 mo, requires the administration of both 17 beta-estradiol and either 5 alpha-androstane-3 alpha, 17 beta-diol or dihydrotestosterone. Testosterone and 17 beta-estradiol, either singly or in combination, did not produce the hyperplastic condition in intact or castrated beagles. The experimentally induced prostatic hyperplasia is identical in pathology to the glandular hyperplasia that occurs naturally in the aging dog with intact testes. However, cystic hyperplasia was not produced by any of the treatments tested in young animals.

Spontaneous benign prostatic hyperplasia in the beagle. Age-associated changes in serum hormone levels, and the morphology and secretory function of the canine prostate.

This paper is a cross-sectional study of spontaneous benign prostatic hyperplasia (BPH) in a single canine species. The effects of aging and hormonal changes on the growth, histology, and glandular secretory function of the canine prostate were studied in 42 male beagles ranging in age from 8 mo to 9 yr. The beagle prostate enlarges for at least 6 yr, whether normal or hyperplastic. In contrast, prostatic secretory function, determined by ejaculate volume and total ejaculate protein, declines markedly after 4 yr of age. These reciprocal growth and functional changes in the prostate are closely associated with a progressive increase in the incidence of BPH, which is already apparent in some dogs by age two. With age there is a modest decrease in serum androgen levels with no apparent change in serum 17 beta-estradiol levels. This suggests that the growth and functional changes that are associated with the development of BPH and are initiated very early in life reflect an altered sensitivity of the prostate to serum androgens or a response to the relative decrease in the serum androgen to estrogen ratio.

Sarcoma in a hamster inoculated with BK virus, a human papovavirus.

An undifferentiated sarcoma occurred in 1 of 52 hamsters inoculated when newborn with BK virus (BKV), A SIMIAN VIRUS 40 (SV40)-related human papovavirus. It was transplantable and grew in tissue culture. Sera of tumor-bearing hamsters were without antibodies reactive to BKV virion antigens in hemagglutination-inhibition and neutralizationtexts, but contained antibodies reactive in immunofluorescence (IF) tests to SV40 T antigen in SV40-TRANSFORMED CELLS AND TO ANTIGENS IN CELLS ACUTELY INFECTED WITH BKV or SV40. The IF reaction between tumor cells and sera of tumor-bearing hamsters was minimal in texts of tumor cells of an early passage but satisfactory in tests of cells from a later passage. Fusion of tumor cells with permissive (monkey and human) cells, induced by inactivated Sendai virus, did not lead to recovery of infectious BKV. Immunization of hamster with BKV or SV40 failed to protect against challenge with tumor cells. There was considerable cross-reactivity between the T antigens of BKV and SV40 viruses

Histopathology of neoplastic and nonneoplastic hepatic lesions in mice fed diets containing tetrachlorvinphos.

Tetrachlorvinphos was fed at 8,000 or 16,000 ppm in diets to male and female (C57BL/6N X C3H/HeN)F1 mice for 80 weeks. Surviving mice were killed at 92 weeks, and all mice were completely necropsied. A high incidence of unusual nonneoplastic hepatic lesions in treated mice was present and characterized by pericellular fibrosis, hepatocyte nuclear pleomorphism, and intrasinusoidal foci of macrophages with intracytoplasmic crystalline structures. From 84 to 94% of the treated male mice and from 21 to 23% of the treated females had hepatocellular neoplasms. Only 17% of the control males and 7% of the control females had liver tumors. The induced tumors were frequently multiple in the liver, whereas the tumors in the controls were usually singular. The morphology of 241 liver tumors in 110 treated mice was different from that of tumors in controls. Liver tumors in control mice were generally composed of small basophillic hepatocytes. In treated mice, tumors were hepatocellular carcinomas composed of solid sheets of large basophilic or eosinophilic hepatocytes. Foci of prominent trabecular formation were seen in 51 tumors. Fifteen tumors were composed of small basophilic hepatocytes with oval cells interposed among them. Foci of capillary formation were noted in 3 of these tumors. In addition, 7 more typical hemangiosarcomas forming sinusoids and with thrombosis were observed.

Induction of liver tumor in Sherman strain female rats by polychlorinated biphenyl aroclor 1260.

Sherman strain female rats (200) were fed 100 ppm of polychlorinated biphenyl (Aroclor 1260) for apporximately 21 months, and 200 female rats were kept as controls. The rats were killed when 23 months old. Twenty-six of 184 experimental animals and 1 of 173 controls had hepatocellular carcinomas. None of the controls but 146 of 184 experimental rats had neoplastic nodules in their livers, and areas of hepatocellular alteration were noted in 28 of 173 controls and 182 of 184 experimental animals. Thus the polychlorinated biphenyl Aroclor 1260, when fed in the diet, had a hepatocarcinogenic effect in these rats. The incidence of tumors in other organs did not differ appreciably between the experimental and control groups.

Long-term effect of 2-hydroxyethyl retinamide on urinary bladder carcinogenesis and tumor transplantation in Fischer 344 rats.

The effects of HER upon early and late stages of BBN-induced bladder cancer in rats were examined. Female Fischer 344 rats were administered HER in the diet either before and during or continuously after BBN administration and were monitored periodically for up to 2 years. The total dose of BBN was 600 mg administered over a 6-week period. In a separate experiment, the effects of HER administration to syngeneic recipients of a transplanted primary bladder cancer were examined. No effects on neoplastic development were observed as the result of HER treatment before and during carcinogen administration. However, at the 1-year sacrifice, there was a significant increase in bladder tumor incidence in the animals receiving BBN followed by continuous retinoid treatment versus animals receiving BBN only. At the 2-year sacrifice, there was a significant increase in tumor progression in the continuous retinoid group versus the animals receiving BBN alone, based upon grading and staging of tumors, although tumor incidences were not significantly different. In the transplantation experiment, more recipients (9/20 versus 2/20) receiving continuous HER had large, anaplastic tumors following 9 months of observation than did control animals. This study supports the view that retinoids should not be considered as only inhibitors of carcinogenesis, but rather as modifiers which vary in their effects depending upon factors yet to be understood.

Complement-like activity in the sea star, Asterias forbesi.

The coelomic fluid (CF) of Asterias forbesi was examined for the presence of complement-like activity. Cell-free CF contains hemolytic activity for unsensitized rabbit erythrocytes (E) but not unsensitized or antibody-coated sheep E. Target E sensitivity is not dependent upon phylogenetic proximity of erythrocyte species to Asterias. The activity is optimally assayed at 25 degrees C, has a sigmoidal dose-response curve, and is heat-sensitive (56 degrees C). The activity is divalent cation dependent, although Ca++ and Mg++ are not required. Nonlytic CF does not contain an inhibitor; rather, combining nonlytic and lytic CFs results in an increase in hemolysis. Activity can be consumed by treatment with zymosan, pronase, trypsin, and PMSF. Enzymatic desialidation converts sheep E into activators of the hemolytic pathway. No phospholipase activity is present in CF. Biological function is demonstrated by bactericidal activity against Vibrio tubiashii by lytic CF. These results suggest that a primitive complement system is operating in Asterias.

Longevity and age-related pathology of LVG outbred golden Syrian hamsters (Mesocricetus auratus).

A colony of male Lakeview Golden (LVG) Syrian hamsters has been maintained for the last nine years as a source of various tissues for cellular aging studies. Observations on this colony also yielded data on survival time and physical and pathological manifestations of aging in this strain. Based on 150 spontaneous deaths, the median life span was found to be 19.5 months. The maximum life span was 36 months and the minimum 6 months. A cross-sectional pathological survey of sacrificed and spontaneously dying members of the population revealed a low rate of neoplasia and a variety of degenerative lesions that increased with age. These observations of a varied pathology and a low frequency of neoplasia provide justification for the continued development of the male LVG Syrian hamster as an animal model system for use in studies on the mechanism of both in vivo and in vitro aging.

Intestinal Cryptosporidium sp. infection in the Egyptian tortoise, Testudo kleinmanni.

An adult Egyptian tortoise (Testudo kleinmanni) presented with clinical signs of enteritis and died 5 weeks after initiation of antibiotic therapy. Histological examination of the small intestine revealed heavy infection with Cryptosporidium sp.; over 80% of epithelial cells harboured the pathogen. No Cryptosporidium developmental stages were present in the stomach or the lungs. The intestinal lamina propria and mucosa were infiltrated by heterophils, lymphocytes and macrophages. The present study constitutes the first report of Cryptosporidium sp. infection in T. kleinmanni, and the first histological documentation of intestinal cryptosporidiosis in Chelonia.

Long term follow-up of transcatheter embolization with autologous clot, oxycel and gelfoam in domestic swine.

Transcatheter embolization of the distal gastrosplenic artery as well as the distal right renal artery or one of its bifurcational branches was performed in 9 domestic swine. The animals were embolized with fresh autologous clot, oxycel or gelfoam in groups of 3. The embolic material was opacified with tantalum in several animals. At 4 months, none of the initial occlusions was sustained and recanalization without residuals was found in the left gastroepipolic artery with only one minor exception. Organized thrombi as sole vascular residuals regardless of embolic substance were found in both the terminal splenic artery as well as in the right renal artery distribution in various degrees together with infarcts in both organs. No trace of either oxycel or gelfoam remained, nor tissue reaction against either material. All 3 agents are therefore regarded equivalent in their long term effects and are not suitable for permanent vascular occlusion.

Transcatheter embolization with microfibrillar collagen in swine.

Transcatheter embolization of the gastrosplenic and renal arteries was performed in 7 domestic swine with suspensions of microfibrillar collagen (MFC), a recently developed topical hemostatic agent. Embolized vessels remained occluded 2 days following embolization. Recanalization occurred by 14 days, although some occlusion in distal vessel persisted at 3 months. Pathologically a marked granulomatous arteritis was noted at 14 days which resolved by 3 months. Gastric ulcers or infarcts were present in two animals. The severe vasculitis and gastric pathology observed with MFC in this study would seem to preclude its use as a general embolic agent. It may be useful, however, in the preoperative embolization of neoplasms, especially in pediatric patients since its physical characteristics allow it to be easily injected through small diameter catheters.

Metrizamide, the ideal radiopaque filling material for detachable silicone balloon embolization.

Porcine visceral and extremity arteries were embolized with detachable silastic balloons; 10 balloons were filled with isoosmolar metrizamide, five were filled with 30% meglumine-sodium diatrizoate and five were filled with 3:1 mixtures of blood and 76% meglumine-sodium diatrizoate. Follow-up radiographs were obtained weekly for 2 weeks, at 4 weeks and at 5 months. At 3 months, arteriography was performed. All balloons occluded the vessel completely upon detachment. Balloons filled with metrizamide did not change their volume or radiopacity during the entire observation period and all remained inflated. The balloons filled with diatrizoate salts enlarged by osmotic growth during the first two weeks and there was a decrease in opacity. Thereafter, one balloon filled with 30% diatrizoate salt solution and one filled with blood-76% diatrizoate deflated. In the former, the embolized artery remained occluded, while in the latter, the vessel reopened and the balloon was found incorporated into the vessel wall at the site of detachment. It is concluded that isoosmolar metrizamide is an ideal filler for detachable silastic balloons since it does not lead to changes in volume or radiopacity and also guarantees long-term vascular occlusion.

Therapeutic embolization with detachable silicone balloons: long-term effects in swine.

Twenty-one embolizations were performed in 12 swine using a detachable silicone balloon-catheter system. In 11 embolizations, balloons were filled with 60% meglumine sodium diatrizoate (R-60); 30% meglumine sodium diatrizoate (R-30) was used in 10 embolizations. Serial radiographs were obtained to determine the duration of balloon inflation. Repeat angiography and autopsy examinations were performed three to six months following embolization. Eighty percent of balloons filled with R-30 were still inflated after 10 days, as opposed to 27% of the balloons filled with R-60. Balloons which remained inflated for more than 10 days caused permanent occlusion of the embolized arteries. The vessels were occluded precisely at the point at which the balloons were initially attached. Pathologically, the occluded vessels exhibited organized thrombi with minimal inflammation. Detachable balloons appear to be an effective, safe method of performing selective vascular occlusion in many circulatory systems. Careful control of the volume and osmolarity of the contrast medium used to inflate the balloons produces permanent arterial occlusion.

Organ ablation by fluid emboli. An experimental study comparing two solidifying liquids.

Embolization for ablation of organs and tumor infarction requires uniform permanent occlusion of the distal vasculature. This is best accomplished through the use of solidifying liquids. The study on 15 dogs reported here compares the degree of peripheral vascular embolization and its relation to tissue infarction both acutely and chronically following embolization of the renal arteries with two solidifying liquids, a low viscosity silicone and the occlusion gel Ethibloc. Silicone produced quite uniform distal distribution including 50 to 80% (mean 66%) of renal glomeruli, whereas Ethibloc occluded more proximally and reached only 10 to 50% (mean 22%) of all glomeruli. After three months complete cortical infarction of all nine kidneys embolized with silicone was found, whereas two of the three kidneys embolized with Ethibloc retained nests of viable glomeruli. Balloon occlusion of the entire renal artery inflow during embolization prevented distal venous emboli whereas partial inflow occlusion allowed systemic venous embolization. It is concluded that due to its more uniform distal penetration low viscosity silicone is a more suitable embolization agent than Ethibloc for organ ablation. Total arterial inflow occlusion during embolization effectively prevents systemic venous embolization.

In vivo and in vitro 31P-NMR preliminary studies of the VX-2 carcinoma in rabbits.

In vivo and in vitro 31P-NMR spectroscopy was used to study the high energy phosphate metabolism of VX-2 tumors implanted into rabbit liver, kidney, and hind-limb muscle. Tumors, at various stages of growth, were first examined by in vivo 31P-NMR spectroscopy, then they were excised and underwent histologic examination and biochemical analysis; both in vitro 31P-NMR and standard enzymatic techniques were used. There was good correlation among the in vivo NMR spectra, the in vitro NMR data, and the biochemical analyses. Although the tumor spectra showed characteristics similar to those reported in the other tumor models, there was a striking variability in the spectra obtained from tumors implanted in the same site and from different sites. There was poor correlation between the degree of necrosis in the tumor and the tumor pH and between the Pi:ATP ratio and necrosis. This variability has important implications for the potential value of using 31P-NMR spectroscopy to monitor tumor growth and therapy in vivo.

Multimodality correlative study of canine brain tumors. Proton magnetic resonance spectroscopy, positron emission tomography, and histology.

RATIONALE AND OBJECTIVES: Structural/functional relationships in an induced canine brain tumor were studied using proton-magnetic resonance spectroscopy (1H-MRS), positron emission tomography (PET), and histology. METHODS: Proton-MRS and PET data of implanted canine brain tumors were correlated with quantitative analysis of the tissue composition within the MRS and PET regions of interest (ROIs). Linear regression analysis was employed to correlate the 1H-MRS and PET data with the percent tumor and the percent total lesion (comprising tumor plus associated pathology ie, edema, cysts, hemorrhage, inflammation) within the ROI. RESULTS: Using 1H-MRS, N-acetyl aspartate concentrations were indirectly correlated with the amount of tumor (P = .058), as well as the amount of tumor plus associated pathology (P = .032) within the ROI. Total creatine concentrations were indirectly correlated with the amount of tumor and the amount of tumor plus associated pathology within the ROI (P < .05). Lactate concentrations were directly correlated with the amount of tumor (P = .053) and the amount of tumor plus associated pathology (P = .058) within the ROI. Using PET, Oxygen metabolic rates were indirectly correlated with the amount of tumor and with the amount of tumor plus associated pathology within the ROI (P < .05). Glucose metabolic rates were directly correlated with both the amount of tumor and with the amount of tumor plus associated pathology at P < .05. Proton-MRS measured concentrations of choline and PET measured values for blood flow, and oxygen extraction showed correlations with the amount of tumor and with the amount of tumor plus associated pathology at P > or = .08. CONCLUSIONS: The PET and MRS data were complementary with respect to suggesting anaerobic glucose metabolism for the tumor. Unlike other tumors, no increase in choline was noted in the canine tumor.

Soy of dietary source plays a preventive role against the pathogenesis of prostatitis in rats.

This study examined the effects of diet on the development of prostatitis in male rats. Adult male rats were placed on either of two specially formulated diets which differed from one another by the presence or absence of soy as the protein source. A third group of rats (control) was fed standard laboratory rat chow which also includes soy as a source of protein. After 11 weeks, it was found that rats maintained on soy-free diet developed prostatitis mainly in the lateral lobe of the prostate. Increased severity and incidence of prostatitis in rats maintained on the soy-free diet coincided with a significant decrease in urinary excretion of various phytoestrogens. There was no evidence of prostatitis in rats maintained on soy-containing diets. Urinary excretion of phytoestrogens in rats maintained on soy-containing diet was also not different from controls. These results suggest that soy as a dietary source plays a protective role against the development of prostatitis in rats, and indicate that the ventral, lateral and dorsal lobes of the rat prostate have different sensitivities to alterations in dietary factors.

Testicular steroidogenesis in the aging brown Norway rat.

In seeking an animal model of age-associated changes in the male reproductive tract, we examined the effects of age on the health and testicular steroidogenic activity of the Brown Norway rat, with comparisons made to the Sprague-Dawley rat. When perfused in vitro under conditions of maximally stimulating luteinizing hormone significant age-associated reductions were seen in testosterone production by testes of Sprague-Dawley rats of 21-24 months of age and by testes of Brown Norway rats of 18-30 months of age. Decreases in the capacity of the testes to produce testosterone were reflected in age-associated decreases in both serum testosterone and in testosterone concentration within the seminiferous tubule fluid. In contrast to the Sprague-Dawley rat, changes in steroidogenic activity in the Brown Norway rat were not accompanied by the occurrence of pituitary adenomas, obesity, or testicular tumors. This along with its longevity, make the Brown Norway strain a highly promising model for testicular aging.