Gross pathology and endocrinology of ovarian cysts in bitches.

A total of 73 bitches with ovarian cysts were ovariohysterectomized. Cysts were characterized by gross pathology and endocrine parameters. Therefore, oestradiol-17ß and progesterone concentrations were assessed in cyst-fluid and corresponding blood plasma in each bitch. Our data demonstrated that multiple cysts were often present in a single individual (82%) and that cysts were commonly found on both ovaries (77%). The number of cysts per individual varied from 1 to 35. Most cysts were small in size (range 0.2-4.0 cm in diameter). No cyst was found to produce solely oestradiol-17ß or progesterone. Plasma levels of oestradiol-17ß and progesterone for a given individual were positively correlated with levels of these same hormones in their cyst-fluid (r = 0.334 and p = 0.001 for oestradiol-17ß; r = 0.419 and p < 0.001 for progesterone). Our study is the first to provide a comprehensive evaluation of the gross pathology and endocrinology of ovarian cysts in a larger number of bitches.

Treponema infection associated with genital ulceration in wild baboons.

The authors describe genital alterations and detailed histologic findings in baboons naturally infected with Treponema pallidum. The disease causes moderate to severe genital ulcerations in a population of olive baboons (Papio hamadryas anubis) at Lake Manyara National Park in Tanzania. In a field survey in 2007, 63 individuals of all age classes, both sexes, and different grades of infection were chemically immobilized and sampled. Histology and molecular biological tests were used to detect and identify the organism responsible: a strain similar to T pallidum ssp pertenue, the cause of yaws in humans. Although treponemal infections are not a new phenomenon in nonhuman primates, the infection described here appears to be strictly associated with the anogenital region and results in tissue alterations matching those found in human syphilis infections (caused by T pallidum ssp pallidum), despite the causative pathogen's greater genetic similarity to human yaws-causing strains.

Lactation and menstruation shift the vaginal microbiota in captive rhesus monkeys to be more similar to the male urethral microbiota.

The vaginal microbiota of nonhuman primates differs substantially from humans in terms of Lactobacillus abundance, overall taxonomic diversity, and vaginal pH. Given these differences, it remains unclear in what way the nonhuman primate genital microbiota protects against pathogens, in particular sexually transmitted infections. Considering the effect that microbiota variations can have on disease acquisition and outcome, we examined endogenous and exogenous factors that influence the urogenital microbiota of male and female captive rhesus monkeys. The male urethral (n = 37) and vaginal (n = 194) microbiota of 11 breeding groups were examined in a cross-sectional study. During lactation and menstruation, the vaginal microbiota becomes significantly more diverse and more similar to the microbes observed in the male urethra. Group association and cage-mate (sexual partners) relationships were additionally associated with significant differences in the urogenital microbiota. Our results demonstrate that microbiota considerations are necessary in order to make informed selection of nonhuman primates as translational animal models.

Mating avoidance in female olive baboons (Papio anubis) infected by Treponema pallidum.

Sexually transmitted infections (STIs) are ubiquitous within wild animal populations, yet it remains largely unknown whether animals evolved behavioral avoidance mechanisms in response to STI acquisition. We investigated the mating behavior of a wild population of olive baboons (Papio anubis) infected by the bacterium Treponema pallidum. This pathogen causes highly conspicuous genital ulcerations in males and females, which signal infectious individuals. We analyzed data on 876 mating attempts and associated acceptance or rejection responses in a group of about 170 baboons. Our findings indicate that females are more likely to avoid copulation if either the mating partner or females themselves have ulcerated genitals. We suggest that this outcome is linked to the overall higher choosiness and infection-risk susceptibility typically exhibited by females. Our results show that selection pressures imposed by pathogens induce individual behavioral modifications, leading to altered mate choice and could reduce promiscuity in a wild nonhuman primate population.

Identification, purification, and radioimmunoassay of NB/70K, a human ovarian tumor-associated antigen.

NB/70K, a tumor-associated antigen of human ovarian epithelial tumor Fraction OCA, has been purified and identified as a glycoprotein which is stable in 0.6 M perchloric acid, binds to concanavalin A, and migrates electrophoretically with alpha-like mobility in barbital-buffered agarose at pH 8.6. NB/70K does not appear to contain normal serum, normal ovary, normal lung, or carcinoembryonic antigen-like cross-reacting antigenic determinants as measured by radioimmunoassay. NB/70K has been purified from ovarian antigen Fraction OCA by chromatography on gamma-globulin coupled to Sepharose 4B and by elution from acrylamide gels. NB/70K migrates as a single band with an apparent molecular weight of 70,000 in sodium dodecyl sulfate:acrylamide gel electrophoresis. A rabbit antibody raised against NB/70K was able to precipitate a polypeptide with a molecular weight of 70,000 as visualized by autoradiography of sodium dodecyl sulfate:acrylamide gels. A radioimmunoassay has been developed for measuring NB/70K activity, using Staphylococcus aureus protein A as a precipitating agent.

Tumor antigen NB/70K and CA 125 levels in the blood of preoperative ovarian cancer patients and controls: a preliminary report of the use of the NB12123 and CA 125 radioimmunoassays alone and in combination.

The NB12123 and CA125 radioimmunoassays, murine monoclonal antibody assays for measuring circulating levels of human ovarian tumor associated antigens NB/70K and CA 125, respectively, have been previously described. In the present study, preoperative serum samples were obtained from patients undergoing laparotomy for benign neoplastic ovarian tumors (N = 16), cancer of the cervix (N = 22), cancer of the uterus (N = 20), and cancer of the ovary (N = 47). Controls (N = 50) were obtained from healthy blood bank donors. No correlation was observed between the levels of NB/70K and CA 125 in these samples (r2 = .079, linear regression analysis). In general, increasing levels of both antigens were present with increasing tumor burden and higher histological grade. In addition, both markers were most elevated in the serum of ovarian cancer patients with serous and unclassified adenocarcinomas. Using 40 AU and 35 unit cut-offs for the NB/70K and CA 125 assay, respectively, overall specificity for healthy controls and patients with benign diseases approaches 100%. The combined sensitivity of the assays for ovarian cancer patient sera in this study indicates that the assays may be helpful in establishing a pre operative diagnosis of ovarian cancer. Complementarity of the NB/70K and CA 125 assays has been demonstrated, indicating that one or both assays may be used to monitor as many as 85% of ovarian cancer patients.

[Treatment of bitches with ovarian cysts using human chorionic gonadotropin-releasing hormone analogue. A case series of 30 bitches]. / Therapie von Hündinnen mit Ovarialzysten durch humanes Choriongonadotropin und Gonadotropin-Releasing-Hormon-Analogon. Eine Fallserie von 30 Hündinnen.

OBJECTIVE: Ovarian cysts have great clinical relevance in bitches. Currently, ovariohysterectomy is regarded as the gold standard, but there is a paucity of information on the aetiology and hormonal treatment in this species. Standardised protocols for non-surgical treatment are, however, virtually non-existent. Reports on the success of hormonal therapy are rare and generally restricted to individual case reports. The objective of the present study was to determine the success rate of human chorionic gonadotropin (hCG) or the gonadotropin-releasing hormone analogue buserelin in a larger cohort of bitches. MATERIAL AND METHODS: A total of 30 bitches with ovarian cysts were treated with a maximum of three attempts per individual, utilising different protocols of the hCG and/or buserelin treatment. RESULTS: Hormonal therapy was successful in 63% of the treated cases. There was no significant difference between the success rates of the hCG- and buserelin-based protocols. The first treatment attempted had a success rate of 40%, with 33% and 67% for the second and third treatments, respectively. The success of conservative therapy failed in the first treatment attempt in two cases, after the second in seven cases, and after the third attempt in one bitch. In these 10 cases, an ovariohysterectomy was performed. CONCLUSION AND CLINICAL RELEVANCE: The hormonal therapy of ovarian cysts in bitches provides an acceptable alternative to the current gold standard of ovariohysterectomy, especially to avoid negative side-effects of spaying. However, conservative therapy requires a pre-interventional health check to exclude uteropathies and oestrogen-induced changes in the haemogram or blood chemistry. Compared to the surgical treatment, there is the chance of recrudescence.

Monoclonal antibody assays for measuring ovarian tumor antigen in blood. Detection of NB/70K in patients with ovarian cancer and nongynecologic diseases.

Blood levels of human ovarian tumor antigen NB/70K were measured using four different monoclonal anti-NB/70K antibody radioimmunoassays (NB12123, NB12913, NB13834, and NB13831 assays). Four hundred thirty-two blood samples were obtained from apparently disease-free controls, from patients with benign and malignant ovarian tumors, and from patients with benign nontumorous and malignant diseases of the breast, lung, and gastrointestinal systems. The means, medians, and percent of samples that had elevated levels of NB/70K were calculated for each group of patients or controls for each assay. For all control versus malignant disease comparisons, there were statistically significant differences in all assays. For all benign versus malignant disease comparisons in the ovary, breast, lung, and gastrointestinal systems, there were statistically significant differences in all assays with the exception of the benign versus malignant gastrointestinal disease comparison in the NB12123 assay. Elevated NB/70K levels were detected in blood from ovarian cancer patients, almost all of whom had adenocarcinomas. Elevated NB/70K levels were also detected in blood samples from patients with adenocarcinoma, squamous, and clear cell carcinomas of the lung as well as in adenocarcinoma and ductal carcinoma of the breast. These results indicate that NB/70K is a marker for different pathologic types of malignancies.

Clinical evaluation of ovarian tumor antigen NB/70K: monoclonal antibody assays for distinguishing ovarian cancer from other gynecologic disease.

Circulating human ovarian tumor antigen NB/70K levels were assessed with four monoclonal antibody radioimmunoassays. A total of 844 blood samples from patients with ovarian cancer and gynecologic control subjects was evaluated to determine the specificity of each of the four assays for ovarian cancer. It was determined that the mean and percent positivity for patients with ovarian cancer were significantly higher than those values for all control groups. When clinical parameters of the patients with ovarian cancer were examined, it was found that NB/70K appeared to be elevated in patients with all of the pathologic types of early stage, low-grade epithelial ovarian cancers studied. One of the four radioimmunoassays (the NB12123 assay) was capable of detecting elevated blood NB/70K levels in greater than 50% of patients with early stage ovarian malignancies. The NB12123 assay was also able to detect NB/70K in the blood of 45% (9 of 20) of patients with stage I, well-differentiated ovarian cancer. These results indicate that NB/70K may be a useful marker for the early detection of localized tumors as well as for monitoring patients with ovarian cancer, as has been demonstrated previously. In addition, NB/70K appears to be a marker for all stages, grades, and pathologic types of human ovarian epithelial tumors.

Quantitation of antigens in normal and malignant ovarian tissue.

Evidence is presented that at least one of the antigens of human ovarian cancer tissue which appeared to be tumor-associated in immunodiffusion and immunoelectrophoresis experiments actually represents a quantitative rather than a qualitative difference between normal and malignant tissue. A glucoprotein band (Rf equals 0.01) believed to contain at least one tumor-associated antigen was isolated by disc-gel electrophoresis with 5.6 per cent SDS-acrylamide and was used to immunize rabbits. Immunodiffusion and immunoelectrophoresis experiments with the resulting antiserum indicated that the glycoprotein band contained two antigens, one which was present in normal extracts at a concentration approximately one tenth of that in tumor extracts and another which was detectable only in tumor tissue. The tenfold difference between normal and tumor tissue was confirmed by studies of the appearance and disappearance of the glycoprotein band when acrylamide gel electrophoresis was performed on varying amounts of normal and tumor extracts.

An improved radioimmunoassay for human ovarian tumor antigen NB/70K.

An improved assay for the measurement of human ovarian tumor antigen NB/70K (triton NB/70K assay) has been developed. This assay makes the accurate and reproducible estimation of serum NB/70K possible. Freezing and thawing of serum up to three times or refrigeration of diluted serum up to 7 days does not significantly alter the NB/70K levels detected by the triton NB/70K assay. NB/70K levels in different volumes of the same sample showed a linear relationship to volume, with a correlation coefficient usually above 0.98.

Purification of human ovarian tumor-associated antigen and demonstration of circulating tumor antigen in patients with advanced ovarian malignancy.

Human ovarian tumor-associated antigen (TAA) has been purified from ovarian tumor tissue by affinity chromatography on concanavallin A-Sepharose and three different gamma globulin-Sepharose columns. The resulting ovarian TAA appears to be contaminated by one normal antigen or family of antigens. Rabbit antiserum prepared against this purified ovarian TAA (antiserum 404) was coupled to CNBr-activated Sepharose 4B. This coupled Sepharose was added to fractionated serum from ovarian cancer patients with Stage III and IV malignancy. Bound protein was eluted with 0.2M glycine buffer and tested against antiserum 404. The bound protein contained TAA identical to the TAA isolated from ovarian tumor tissue.

The development of a double-antibody radioimmunoassay for detecting ovarian tumor-associated antigen fraction OCA in plasma.

Ovarian tumor-associated antigen isolated from human tumor tissue was shown to have a different mobility from that of carcinoembryonic antigen (CEA) in both acrylamide gel electrophoresis and immunoelectrophoresis in agarose. The ovarian tumor antigen is composed of six species with different electrophoretic mobility in acrylamide gel electrophoresis. Three of these species were detected in Sephadex G-100 ovarian fraction OCA (from the void volume peak) and the other three species of lower apparent molecular weight were detected in fraction OCD (from the second peak). Fractions OCA and OCD did not share common antigenic determinations as determined by immunodiffusion. CEA was shown to share antigenic determinants with both OCA and OCD. A double-antibody radioimmunoassay capable of detecting nanogram quantities of plasma OCA was developed. In a preliminary study of ovarian cancer patients, OCA appeared to be a more sensitive marker for ovarian cancer than CEA. There was vitually no correlation (r2 - 0.1) between OCA and CEA levels in these patients, as determined by radioimmunoassay.

Diaphragmatic peritoneal biopsy.

For the past two years, this technique has been used without complications in all patients in whom direct or random biopsies of the diaphragmatic peritoneal surfaces are indicated. Several advantages of this technique include: 1, specimens taken for biopsy from all peritoneal surfaces, including infracolic and pelvic, can be easily obtained in this manner; 2, surgical clips are inert, hemostatic and easy to apply; 3, in reassessment operations, previously placed clips lead the surgeon to areas where implants or occult metastases were initially found, and 4, the clips could potentially serve as anatomic markers in planning adjuvant treatment, especially irradiation therapy.

Regulation of capillary blood flow and oxygen supply in skeletal muscle in dogs during hypoxaemia.

1. Multiwire surface electrodes were used to measure local hydrogen clearance curves and tissue PO2 in vivo. Evaluation of the initial slopes of the hydrogen clearance curves enabled the measurement of capillary blood flow and its distribution. 2. Capillary blood flow and tissue PO2 frequency distribution histograms were measured in the m. sartorius of anaesthetized, relaxed mongrel dogs under conditions of normoxic (Fi, O2 = 0.3) and hypoxic (Fi, O2 = 0.15 and 0.1) artificial ventilation. 3. Stepwise hypoxaemia (hypoxic hypoxia) induced an increasing discrepancy between capillary blood flow and arterial blood flow. The former decreased by 6% whereas the latter increased by 86%. 4. PO2 histograms provided no evidence of cellular anoxia even at Fi,O2 = 0.1. Capillary blood flow histograms suggested a redistribution of the local pattern of flow. 5. A 34.7% reduction of O2 consumption was observed as the result of severe hypoxaemia. 6. The concept of heterogeneity of capillary blood flow as a functional O2 reserve is presented, together with evidence for oxygen-dependent regulation of capillary blood flow and oxygen consumption.