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.

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.

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.

[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.

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.

Cloning and characterization of the breakpoint regions of a chromosome 11;18 translocation in a patient with hamartoma of the retinal pigment epithelium.

Mutations of various tumor suppressor genes, e.g., PTEN, TSC1, and TSC2, are known to be responsible for different inherited diseases presenting with multiple hamartomas, a benign tumor resembling neoplasia that results from faulty organ development. Combined hamartoma of the retinal pigment epithelium (RPE) and retina is a rare, congenital, focal malformation of the fundus. So far, no disease gene has been associated with this disorder. By molecular analysis of an apparently balanced and reciprocal translocation between the short arms of chromosomes 11 and 18, t(11;18)(p13;p11.31), in a patient with hamartoma of the RPE and retina, we selected PAC clones crossing the breakpoints on both derivative chromosomes 11 and 18. For the overlapping chromosome 11 clone, two EST clusters were identified, suggesting the existence of at least two genes in the breakpoint region. We constructed a PAC contig and showed that at least three exons of a novel gene map to the breakpoint region on chromosome 18. Based on the results of FISH analysis with the PAC clones of this contig, we suggest the occurrence of a complex rearrangement.

Coordinate elevation of serum markers in ovarian cancer but not in benign disease.

Effective screening for occult ovarian cancer will require a strategy that is both sensitive and specific. Preliminary data suggest that CA 125 is elevated at diagnosis in a majority of patients with ovarian cancer. Although CA 125 is sufficiently specific to prompt its evaluation as one component of a strategy to detect ovarian cancer in postmenopausal women, a further improvement in specificity would facilitate cost-effective screening. In an attempt to develop a more specific screening strategy, multiple markers were assayed in a panel of sera from 47 patients with ovarian cancer and in a separate panel of sera from 50 individuals with benign disease whose serum CA 125 levels exceeded 35 U/ml. Among the patients with ovarian cancer, elevations of CA 125 (greater than 35 U/ml) were observed in 91%, CA 15-3 (greater than 30 U/ml) in 57%, TAG 72 (greater than 10 U/ml) in 49%, placental alkaline phosphatase (PLAP) in 25%, human milk fat globule protein (HMFG) 1 in 77%, HMFG2 in 62%, and NB/70K in 57%. Among the 50 sera selected from patients with benign disease, CA 125 was more than 35 U/ml in 100% and more than 65 U/ml in 42%. Among those patients with benign disease and elevated CA 125, NB/70K was elevated in 62%, HMFG1 in 26%, and HMFG2 in 12%, whereas TAG 72 and CA 15-3 were elevated in only 6% and 2%, respectively. In addition PLAP appeared promising; elevated enzyme levels were not found in the benign disease group. Among patients with ovarian cancer with CA 125 levels more than 35 U/ml, either TAG 72 or CA 15-3 was elevated in 77%. In the false-positive group, only 6% had elevations of one or the other marker. The CA 125 levels in cancer patients were, however, substantially greater than in patients with benign disease. If sera from patients with ovarian cancer were diluted to a range comparable to that found in benign disease, at least one of the two confirmatory tests was elevated in 63% of the samples from the malignant cases. Consequently, use of CA 15-3 and TAG 72 in combination with CA 125 can increase the apparent specificity of the CA 125 assay for distinguishing malignant from benign disease. Prospective studies will be required to test critically whether the use of additional serum markers in combination with the CA 125 assay would contribute to the specificity of a cost-effective screening strategy for ovarian cancer.

Local oxygen supply and blood flow regulation in contracting muscle in dogs and rabbits.

1. Multiwire surface electrodes were used to measure local hydrogen clearance curves and tissues PO2 in the sartorius muscle in dogs under resting conditions and during stimulation of the muscle at 1, 2, 4, 8 and 20 Hz via the femoral nerve. Tissue oxygen supply was assessed by means of PO2 histograms; evaluation of the initial slopes of the hydrogen clearance curves enabled the measurement of capillary blood flow. 2. In a further model, the analysis of hydrogen clearance curves measured in the femoral vein using intravascular needle electrodes in rabbits enabled the distribution of blood flow to be evaluated both under resting conditions and during direct 2 Hz stimulation of the vastus medialis muscle. 3. Increased oxygen consumption, induced by stimulation, caused increases in capillary flow which were not necessarily accompanied by augmentation of femoral artery flow. 4. PO2 histograms provided no evidence of cellular anoxia even at the maximum level of oxygen consumption. 5. A two-compartment distribution of flow was measured under resting conditions, whereas only one compartment could be resolved during 2 Hz stimulation of the vastus medialis muscle in the rabbit experiments. A clear redistribution of flow was observed in the absence of any increase in total flow. 6. A model for oxygen-dependent regulation of capillary blood flow involving high-flow and normal-flow compartments is proposed.

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.

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.

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.

Monoclonal antibodies against human ovarian tumor associated antigen NB/70K: preparation and use in a radioimmunoassay for measuring NB/70K in serum.

Murine monoclonal antibodies (MCAs) against human ovarian tumor associated antigen NB/70K have been prepared. One of these MCAs, NB12123, was chosen for the development of a radioimmunoassay for measuring serum NB/70K levels. In this assay, the average NB/70K level in 75 normal, healthy controls was 11.9 activity units (AU) with an SD of 14.9 AU. The normal cut off value for this assay was set at 45 AU (mean +2 SD). 24 of 46 (52%) ovarian cancer patients, 7 of 18 (39%) patients with benign ovarian cysts or tumors and 3 of 85 (4%) control samples had elevated serum NB/70K levels. Comparison of NB/70K levels measured in the NB12123 assay with levels measured in an assay using a polyclonal antiNB/70K previously developed in our laboratory [13] indicated that although both assays had approximately the same percentage of positive ovarian cancer patient samples, there appeared to be no correlation between the absolute NB/70K levels measured by the two assays. The rank of ovarian cancer patient samples was also different for the two assays. Also, almost 40% of patients with benign ovarian cysts and tumors had elevated serum NB/70K levels as measured by the NB12123 assay as compared to 0% for the polyclonal assay. Reciprocal cross-blocking experiments, absorption studies, and immune precipitate analysis indicated that both the monoclonal NB12123 assay and the polyclonal antiNB/70K assay measured the same population of NB/70K molecules. However, the polyclonal antibody recognizes epitopes in addition to that recognized by NB12123. Taken together, these results suggest that the epitope recognized by NB12123 is not as specific for malignant ovarian tumors as the epitope(s) recognized by polyclonal antiNB/70K and/or that more than the one epitope detected by the MCA is responsible for the specificity for ovarian cancer of the polyclonal NB/70K assay. In spite of this, the greater sensitivity and range of the monoclonal NB12123 assay make it possible to monitor serum NB/70K levels in ovarian cancer patients. In four patients examined, the fluctuating serum NB/70K levels appeared to correlate well with clinical status.

A study of the NB/7OK and CA 125 monoclonal antibody radioimmunoassays for measuring serum antigen levels in ovarian cancer patients.

Serum levels of tumor antigens NB/7OK and CA 125 were determined in 101 samples by radioimmunoassays with the use of murine monoclonal antibodies. Among serum samples from ovarian cancer patients, elevated NB/7OK levels were found in 87% of samples that contained elevated CA 125 levels. With either assay, only 2% of patients with nonmalignant diseases had elevated antigen levels. No quantitative correlation was found, however, between levels of NB/7OK and CA 125. When antigen present in serum was purified by gel filtration on Sephacryl S-200, CA 125 eluted with an apparent molecular weight in excess of 100 kilodaltons whereas NB/7OK eluted with an apparent molecular weight of 70 kilodaltons. Thus the NB/7OK and CA 125 radioimmunoassays appear to measure two different populations of antigenic material.

Detection of ovarian cancer by the humoral leukocyte adherence inhibition test using a purified tumor-associated antigen.

The defined, purified ovarian cancer-associated antigen, NB/70K, was used as tumor antigen in the humoral leukocyte adherence inhibition (H-LAI) assay. Bell-shaped dose-response relationships were obtained with increasing concentrations of NB/70K and constant serum concentration from ovarian cancer patients. The concentrations of NB/70K used in this study were 100-250 times less than what had been used in previous H-LAI studies with crude antigen extracts. The response rate of ovarian cancer patients was greatly influenced by the stage of the disease. Thus 75% (6/8) of the patients with disease restricted to the pelvis (stages I and II) reacted while only 20% (5/24) of the patients with more advanced stages (stages III and IV) gave response. Of patients with other gynecological cancers, 17% (1/6) were positive and only 8% (1/13) of patients with other malignant diseases reacted. One of the 11 controls (9%) was found to give positive response. The importance of the present investigation was the finding that a defined, purified, cancer-associated antigen elicited reactivity in the H-LAI assay and that a high sensitivity for detection of early stages of ovarian cancer was obtained with this antigen. The results suggest that TAAs involved in immune recognition of cancer can be identified by the H-LAI assay.

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.

Selectivity for ovarian cancer of an improved serum radioimmunoassay for human ovarian tumor-associated antigen NB/70K.

An improved NB/70K assay which can be used to reproducibly and accurately measure the NB/70K content of unextracted serum samples has been developed. Analysis of pretreatment serum samples has indicated that the NB/70K assay shows selectivity for ovarian cancer with respect to nonmalignant ovarian cysts and tumors as well as controls; if one considers 10 units of NB/70K as a significant level of antigen, then there are no false positives in the benign and control groups, while 10 of 21 in the ovarian cancer group have significant NB/70K levels. When NB/70K levels of ovarian cancer patients are compared to those of patients with non-ovarian malignant disease, only 4 of 23 patients with non-ovarian cancers had significantly elevated NB/70K levels. However, none of these 4 false positives had levels greater than 20 units.