Breakdown of B cell tolerance in a mouse model of systemic lupus erythematosus.

Anti-DNA antibodies, specifically those that stain nuclei in a homogenous nuclear (HN) fashion, are diagnostic of systemic lupus erythematosus (SLE) and the MRL-lpr/lpr SLE murine model. We have used a heavy chain transgene that increases the frequency of anti-HN antibodies to address whether their production in SLE is the consequence of a defect in B cell tolerance. Anti-HN B cells were undetectable in nonautoimmune-prone transgenic mice, but in MRL-lpr/lpr transgenic mice their Ig was evident in the sera and they were readily retrievable as hybridomas. We conclude that nonautoimmune animals actively delete anti-HN-specific B cells, and that MRL-lpr/lpr mice are defective in this process possibly because of the lpr defect in the fas gene.

Fibroblastic Subtype has a Favourable Prognosis in Appendicular Osteosarcoma of Dogs.

Osteosarcoma (OS) is an aggressive malignant bone neoplasm that occurs mostly in the appendicular skeleton of dogs and people. OS is classified based on the presence of malignant stroma and the formation of extracellular matrix into osteoblastic, chondroblastic and fibroblastic forms. This study investigated the correlation between the three histological subtypes of canine OS and clinical outcome. Additionally, we examined whether there was any difference in the immunolabelling of desmin, S100 and neuron-specific enolase (NSE) between the three histological subtypes. Formalin-fixed and paraffin wax-embedded tissues from 87 dogs with primary OS were available for this study. The survival times were correlated with appendicular OS subtypes in dogs that were treated surgically, received adjuvant chemotherapy and had no pulmonary metastasis at the time of diagnosis. Dogs with an appendicular fibroblastic OS had significantly prolonged mean average survival times (546 ± 105 days) in comparison with dogs having appendicular osteoblastic (257 ± 48 days) or appendicular chondroblastic (170 ± 28 days) OS (P = 0.003, Log Rank). The results also revealed that the appendicular chondroblastic subtype is a significant indicator for poor prognosis in dogs compared with the fibroblastic or osteoblastic subtypes (P = 0.006, Cox regression). Moreover, the findings indicated that there was no significant correlation between the localization of desmin, NSE or S100 and histological subtypes. Importantly, dogs with appendicular fibroblastic OS were found to have a better prognosis when compared with dogs with other subtypes. This may suggest that histological subtypes of appendicular OS have diverse behaviour and could be used to categorize patients for risk-based assessment.

Impact of chronic airflow obstruction in a working population.

Data on the individual and collective impact of chronic airflow obstruction at a population level are scarce. In a nationwide survey, dyspnoea, quality of life and missed working days were compared between subjects with and without spirometrically diagnosed chronic airflow obstruction. Subjects aged > or =45 yrs were recruited in French health prevention centres (n = 5,008). Results of pre-bronchodilator spirometry and questionnaires (European Community Respiratory Health Survey-derived questionnaire and European quality of life five-dimension questionnaire) were collected. Adequate datasets were available for 4,764 subjects aged 60+/-10 yrs (only 2% were aged > or =80 yrs). The prevalence of airflow obstruction (forced expiratory volume in one second/forced vital capacity of <0.70) was 7.5%. The vast majority (93.9%) of cases had not been diagnosed previously. Health status was significantly influenced by dyspnoea. Both were associated with the number of missed working days. Despite mild-to-moderate severity, subjects with chronic airflow obstruction exhibited more dyspnoea, poorer quality of life and higher numbers of missed working days (mean 6.71 versus 1.45 days.patient(-1).yr(-1) in patients without airflow obstruction, for the population with no known heart or lung disease). In conclusion, even mild-to-moderate airflow obstruction is associated with an impaired health status, which represents an additional argument in favour of early detection in chronic obstructive pulmonary disease.

[Erionite-induced pleural plaques. Exposition to urban pollution in a female Turkish migrant in Germany]. / Erionitinduzierte Pleuraplaques. Urbane Belastung bei einer türkischen Migrantin.

Erionite is a zeolite mineral of volcanic origin which contains no asbestos. It is found in different regions of the world, including southeast Turkey in ash and dust, from which it can cause inflammatory pleural plaques or malignant pleural mesothelioma (MPM). We report a female Turkish migrant exposed to urban pollution in her home country who decades later suffered from pleural plaques with a nonspecific chronic inflammatory disease. The differential diagnosis of inflammatory pleural plaques was assumed radiologically and confirmed by video-assisted thoracoscopic biopsy. Short-term clinical and radiologic control of the patient will be necessary because of the risk of MPM. For epidemiologic considerations discussed referring to current literature, a growing incidence of this type of disease in migrants from high-risk areas must be reckoned with in Germany, even without exposition to asbestos.

Immunohistochemical Validation of Spontaneously Arising Canine Osteosarcoma as a Model for Human Osteosarcoma.

Osteosarcoma (OS) originates from bone-forming mesenchymal cells and represents one of the primary bone tumours. It is the most common primary bone tumour in dogs and man. The characterization of an appropriate natural disease animal model to study human OS is essential to elucidate the pathogenesis of the disease. This study aimed to validate canine OS as a model for the human disease by evaluating immunohistochemically the expression of markers known to be important in human OS. The immunohistochemical panel included vimentin, alkaline phosphatase (ALP), desmin, S100, neuron-specific enolase (NSE), runt-related transcription factor 2 (Runx2) and bone morphogenetic protein 4 (BMP4). Immunohistochemistry was conducted on formalin-fixed, paraffin wax-embedded tissue sections from 59 dogs with confirmed primary OS. Vimentin, ALP, Runx2 and BMP4 were highly expressed by all tumours, while desmin, S100 and NSE were expressed variably. The findings were similar to those described previously for human OS and suggest that canine OS may represent a useful model for the study of the human disease.

[Palliative bypass surgery]. / Bypasschirurgie zur Palliation.

Impaired intestinal passage considerably reduces quality of life irrespective of the underlying condition. Limited life expectancy and increased operative risk of advanced malignant disease add particular weight to this issue. The indication for operative therapy results from carefully weighing individual incapacity and potential gain vs operative risk and life expectancy. Exactly because life expectancy is quite limited, selection of an effective, low-risk procedure is of utmost importance to benefit the patient.

Influence of different gases used for laparoscopy (helium, carbon dioxide, room air, and xenon) on tumor volume, histomorphology, and leukocyte-tumor-endothelium interaction in intravital microscopy.

BACKGROUND: Previous studies indicate that helium pneumoperitoneum used for laparoscopic surgery suppresses whereas carbon dioxide pneumoperitoneum increases postoperative tumor growth. The pathomechanisms of decreased tumor growth by helium are unknown. This study was designed to examine the effect of the gases helium, carbon dioxide (CO(2)), and air, and xenon, which can be used to induce pneumoperitoneum in laparoscopy on tumor volume, histomorphology, and leukocyte-endothelium interaction measured by intravital microscopy in rats with implanted liver malignoma (Morris hepatoma 3924A). METHODS: In 46 rats, Morris hepatoma 3294A cells were implanted intrahepatically. After implantation, rats were randomized into two main groups. In the first main group, 10 animals were prepared for examination of leukocyte-endothelium interaction by intravital video microscopy and were randomized into two groups. Five days after implantation they underwent laparoscopy using either helium (n = 5) or CO(2) (n = 5). Ten days after implantation the rats underwent intravital video microscopy to assess leukocyte-endothelium interaction in the tumor and liver vessels. In the second main group 36 rats were prepared for examination of tumor volume arid histomorphology. They were randomized into five groups. Five days after implantation they underwent laparoscopy using helium (n = 7), carbon dioxide (n = 7), room air (n = 7), or xenon (n = 8). The control group (n = 7) received anesthesia only. Rats were killed 10 days after tumor implantation to assess tumor volume and histomorphology. RESULTS: Compared to the control group or groups that received CO(2), room air, or xenon for pneumoperitoneum, the establishment of helium pneumoperitoneum caused a significantly smaller tumor volume (Kruskal-Wallis test, p = 0.001; median tumor-volume: control group, 44 mm(3); helium 19 mm(3)). There was no significant difference in histomorphology between the groups. There was only a statistically significant difference in the development of central tumor necrosis in accordance to tumor volume (Mann-Whitney test, p = 0.03). In the tumor samples, roller counts were statistically significantly higher in the helium group compared to the CO(2) group (p = 0.04). For sticker counts, no statistically significant effects due to liver/tumor (p = 0.13) or treatment (p = 0.48) were observed. CONCLUSIONS: There was a significant decrease in tumor volume using helium pneumoperitoneum for laparoscopy compared to the other gases. Here, we demonstrate that suppression of tumor growth is not due to variation of histomorphology. It seems that helium pneumoperitoneum effects a higher leukocyte-endothelium interaction and thereby a higher immune activation. This could be one explanation for the statistically significantly smaller tumor volume after laparoscopy with helium compared to laparoscopy with CO(2).

[Experimental testing of a new coil design for endoluminal MRI applied to the pig stomach]. / Experimentelle Erprobung eines neuen Spulendesigns zur endoluminalen MRT am Beispiel des Schweinemagens.

PURPOSE: Experimental feasibility study of a new MR-Coil concept for enhanced visualization of the gastric wall. MATERIAL AND METHODS: The newly developed single-loop receiver coil for endoluminal imaging (Fraunhofer Institute, St. Ingbert, Germany) was evaluated in 4 explanted pig stomachs in a 1.5T MR unit (Siemens Symphony, Erlangen, Germany) with T1 w and T2 w MR sequences in three planes. The new coil consists of a foldable and self-expanding single loop coil (receiver coil) of a shape memory metal (nitinol). It was covered with a biocompatible material (silicone) to prevent direct contact of the wire with stomach tissue. The coil assumes a circular configuration with a diameter of 8 cm because of its memory metal properties. The flexible characteristics of the material used allow the passage through the instrument channel (13 mm diameter) of a specially designed MR-compatible endoscope. The purpose of our study was to assess feasibility of the coil design as a first step in developing a new endoluminal MRI-concept. Additionally the number and signal intensity of visible gastric wall layers were evaluated and findings were correlated with histopathological results of a pig stomach. RESULTS: The new coil concept was a feasible system in all 4 cases and showed good image quality for analysis. On T1 w images, 3 layers were visible in all cases, and on T2 w images 4 different gastric wall layers were seen in 2 cases. Due to histopathological correlation, the different gastric wall layers were identified as follows: mucosa, submucosa and muscularis propria if three layers were depicted; in cases of 4 visible wall layers, serosa and subserosa could be detected additionally. For each gastric wall layer, a distinct signal intensity was found. CONCLUSION: The new MR coil concept for endoluminal imaging proved to be a feasible technique. Good differentiation of gastric wall layers in the pig stomach could be demonstrated. We have shown that endoscopic MR-imaging with our new coil concept is a valuable technique for the visualization of gastric wall layers. Due to this fact, follow-up studies including assessing safety aspects are necessary to finally conduct an experimental-clinical study on in-vivo human gastric specimens to detect tumor growth and morphology within the gastric wall. Endoscopic MRI may have the potential in the future to overcome today's limitations of diagnostic imaging in gastric cancer.

Retrieval of ureteral calculus using a new method of endoscopic assistance in a cat.

A 9-year-old female spayed domestic short-haired cat presented with ureteral obstruction due to a ureteral calculus 4 cm distal to the renal pelvis. Preoperative creatinine was 844 mmol/L. A novel approach to this condition was utilised whereby a flexible endoscope was passed through a hole made in the renal capsule into the renal pelvis and ureter. The calculus was visualised, and the endoscope was removed. A 1.4 mm flexible grasping forceps was introduced into the proximal ureter through the same hole in the renal capsule and the calculus was removed. The creatinine dropped to 282 micromol/L within 2 weeks of surgery. The cat died of apparently unrelated causes several months after surgery.

[Sun exposure and sun protection behavior and attitudes among the French population]. / Connaissances, attitudes et comportements des adultes vis-à-vis du soleil en France.

INTRODUCTION: The number of new skin cancers has constantly increased in France over the past two decades. The role of sun exposure can partly explain this phenomenon and justifies the development of information and prevention campaigns to change peoples' attitude towards sun bathing. To be effective, we need to know how much information and what attitudes the population currently has with regard to the sun. Although several studies in France have targeted children, little data is available regarding adults. This trial was aimed at pinpointing the knowledge, attitude and behavior of adults regarding sun exposure. MATERIAL AND METHODS: Data were collected during a randomized multicenter study on the prevention and early diagnosis of cutaneous tumors, conducted in 26 Health Centers from 1998 to 2000. Standardized questionnaires were handed to those consulting to assess their knowledge, attitudes and behavior towards sun bathing. The population was composed of 41 143 adults aged over 30, consulting one of the 26 Health Check-up units. Analysis of the data was made using SAS v 6.12 and STATA 7.0 software. Logistic regression identified the explicative factors of knowledge and behavior. All the statistical analyses were considered significant above a threshold of alpha<5%. RESULTS: A total of 33 021 persons filled-in the self-questionnaire. Forty-nine percent were women and 51% were men, with a mean age of 50 years. Geographically, 25% lived in the North-East, 16% in the North-West, 25 p.cent in the South-East and 34% in the South-West. Thirty percent claimed that they tanned without burning and 2% of the population studied had often suffered from sun burn, generally when they were adult. The risks related to sun burn were known, because 92% knew that the sun increased the risk of skin aging and 89% knew that it increased the risk of skin cancer. Regarding sun screens, knowledge was not so good; 42% thought that all products were the same and 53% that they allowed one to sun bathe longer. This knowledge was better in those with fair skins, in those who had a history of sun burn, in women and in those who lived in the northern areas of France. Conversely, knowledge decreased with age and was limited in those aged over 60. Regarding behavior, those with fair skin and who reddened under the sun without tanning, protected themselves more. The women declared they protected themselves more than the men, but they used less sun protective measures (clothing, hats...), other than sun screens, than men. Subjects aged over 60 protected themselves more than younger subjects. Lastly, a personal cutaneous history increased protective behavior, and those from northern France protected themselves more than those from the South. DISCUSSION: This analysis of 33 021 adults aged over 30 shows the good global knowledge of the consequences of sun bathing, but also the lack of knowledge on the interest of using external sun protection and the role of physical means of protection. Attitudes varied depending on gender, age and phototype and also depending on the area where they lived. Despite good knowledge, the most frequent behavior of adults aged over 30 is still not appropriate with differences depending on age, gender and area, which must prompt more appropriate targeting of prevention campaigns according to the populations concerned.

Segregation analysis and variance components analysis of bone mineral density in healthy families.

Bone mineral density (BMD) was measured in 1992-93 in 129 nuclear families, including 258 parents and 183 children, and was analyzed for familial resemblance factors. BMD measurements were adjusted on weight and age. Segregation analysis rejected the monogenic hypothesis and exhibited a strong polygenic component. Variance components analysis was then used to estimate the parameters of a multivariate normal model including an additive polygenic component, a common environment factor, and a residual specific to each individual. The genetic component was independent of sex and age. The common environmental factor was not significant. The variance of the residual specific factor appeared to be a quadratic function of age, reaching its minimum value at 26.4 years. Consequently, the maximum value for heritability (ratio of genetic variance to total variance) is observed at this age (h2 = 0.84). According to this model, the correlation between two relatives is a function of the ages of each individual in the pair.

Monocytes influence the fate of T cells challenged with oxidised low density lipoproteins towards apoptosis or MHC-restricted proliferation.

Atherosclerosis has been implicated in myocardial infarction, stroke and a host of cardiovascular diseases. The presence of activated T lymphocytes and macrophages, and the increased expression of HLA-DR antigen are consistent with the notion of immune activity in the atherosclerotic plaque. The nature of the causative antigen has not been established although oxidised low density lipoproteins (oxLDL) that accumulate in atherosclerotic plaques could fulfil this role. Here, we report that monocytes play a key role in influencing the fate of purified peripheral human T lymphocytes from healthy donors when the cells are exposed to LDL oxidised under the controlled conditions of water radiolysis. Our data showed that oxLDL generated under these conditions were chemoattractants for T cells. However, they induced a state of apoptosis in T lymphocytes cultured in the absence of monocytes. The extent of apoptosis was related to the degree of oxidation of LDL and the time of T cell exposure to oxLDL. OxLDL-dependent apoptosis did not involve a scavenger-like receptor. CD4(+) cells were more sensitive to the apoptotic effect of oxLDL than CD8(+) cells. OxLDL-primed (12 h) autologous monocytes triggered a robust proliferation of T lymphocytes cultured in the absence of oxLDL. The strength of T cell stimulation was related to the degree of oxidation of the LDL used in priming. Heterologous monocytes exposed to oxLDL under similar conditions induced a response that was not different than monocytes exposed to untreated LDL (natLDL) which did not induce T cell proliferation. Fucoidan did not modify the oxLDL-, monocyte-dependent T cell response to proliferation, suggesting that a scavenger-like receptor was not involved. The expression of the HLA-DR marker and the B7.2 protein were up-regulated in monocytes exposed to oxLDL but not to natLDL. The levels of B7.1 were unchanged. Our data are consistent with the notion that monocytes are critical for T cell survival in the presence of oxLDL and MHC-restricted T cell proliferative response to oxLDL.

White matter ischemia on brain SPECT.

Four patients were shown to have ischemic injury to the posterior limb of the internal capsule on brain SPECT with 99mTc-HMPAO. These findings were later corroborated by transmission CT scans in three patients. In the interpretation of high-resolution SPECT imaging of regional cerebral blood flow, it is important to inspect the deep white and gray matter activity for asymmetry and perfusion deficits. The blood flow to the diencephalon, which is critical for brain function, can be imaged with high-resolution brain SPECT. The early ascertainment of ischemic changes in the diencephalon may lead to important patient management decisions.

Modification by cyclic adenosine monophosphate of basolateral membrane chloride conductance in chick retinal pigment epithelium.

PURPOSE: We investigated the hypothesis that cyclic adenosine monophosphate (cAMP) modifies the basolateral membrane chloride conductance of chick retinal pigment epithelium (RPE). METHODS: Placing freshly dissected chick retina-RPE-choroid tissues in a perfusion chamber that allows separate perfusion of its retinal and choroidal sides, the authors examined the effect of choroidal perfusion of forskolin (50 mM), an adenylate cyclase activator, on extracellular and intracellular RPE potentials, resistances, light-evoked responses, and chloride diffusion potentials. RESULTS: Forskolin hyperpolarized the RPE basolateral membrane, decreased the apical/basal membrane resistance ratio, increased the amplitude of the RPE membrane c-wave hyperpolarizations, decreased the amplitude of the transepithelial c-wave, and suppressed the light peak. In addition, forskolin decreased the basolateral membrane chloride diffusion potential by 31%. The effects of forskolin were diminished by pretreatment of the basolateral membrane with DIDS, a chloride channel blocker, or by pretreatment of the apical membrane with bumetanide, a blocker of NaK2Cl cotransport. Transepithelial potential, resistance, and c-wave amplitude were not changed by 1,9-dideoxyforskolin, which does not elevate cAMP levels. CONCLUSIONS: Elevation of cAMP results in diminished basolateral membrane chloride conductance in chick RPE. This could be due to a direct effect on the chloride channel or due to a decrease in intracellular chloride concentration secondary to inhibition of apical membrane NaK2Cl cotransport.

Sub-retinal pigment epithelial deposits in a dominant late-onset retinal degeneration.

PURPOSE: To determine the pathogenesis of an autosomal dominant late-onset retinal degeneration by studies of the retinal histopathology, phenotype of family members, and candidate genes for the disease. METHODS: The retina from an 80-year-old patient donor was prepared for light and electron microscopy, including special stains and immunocytochemistry. Family members were examined clinically and with retinal function tests. Rhodopsin, peripherin/RDS, and TIMP3 genes were screened for mutations, and linkage analysis was performed with short tandem repeat polymorphisms flanking these genes. RESULTS: Affected family members had nyctalopia in the sixth decade of life and severe visual loss developed by the eighth decade. The donor retina showed marked loss of photoreceptors except in the inferior periphery. A thick layer of extracellular deposits was present between the RPE and Bruch's membrane in all retinal regions. A 70-year-old affected family member had a retinopathy resembling retinitis pigmentosa. Her 42-year-old daughter had a patch of punctate yellow-white lesions in one fundus and abnormal dark adaptation. The 50-year-old son of the donor had normal fundi but abnormal dark adaptation and electroretinography. No mutations were detected in the coding sequence of the rhodopsin, peripherin/RDS, and TIMP3 genes. Rhodopsin and TIMP3 were further excluded with linkage analysis. CONCLUSIONS: This novel retinal degeneration shares histopathologic and clinical features with both Sorsby fundus dystrophy and retinitis pigmentosa. The sub-RPE deposits may disrupt the exchange of nutrients and metabolites between the retina and the choriocapillaris, leading to photoreceptor dysfunction and degeneration.

The form and function of the Leydig cells in hypophysectomized rams treated with pituitary extract when spermatogenesis is disrupted by heating the testes.

The morphology and in-vivo function of the Leydig cells were studied in rams when spermatogenesis had been disrupted by a single exposure of the testes 20 days earlier to a temperature of about 42 degrees C for 45 min. To avoid complications due to changed negative feedback from the testes to the pituitary with consequent changes in the degree of gonadotrophic stimulation, ten of the animals (five heated and five unheated) were surgically hypophysectomized when the testes were heated and then treated twice daily with pituitary extract. Six intact rams (three heated and three unheated) were also studied. The heat-affected testes were about half the size of the unheated testes, and blood plasma flow was closely related to testis weight. There were no differences in the testosterone concentrations in spermatic venous blood, testicular lymph or rete testis fluid, or in oestradiol in spermatic venous plasma from heated or unheated testes. Consequently, testosterone secretion by the heat-affected testes was markedly reduced, and the concentrations in jugular blood were also lower in the heat-affected rams than in controls. The volume of the interstitial tissue was less in absolute terms in the heat-affected rams, but it made up a greater fraction of the testes. The absolute volume of the blood plus lymph vessels, and their fraction of the interstitial tissue were lower in the heat-affected testes, although there was no effect on their volume as a fraction of the whole testis. The heat-affected testes of the hormone-treated rams had fewer Leydig cells, but each cell was larger; no equivalent difference was found in the intact rams. However, the dose of pituitary extract chosen was somewhat excessive, as there were higher than normal concentrations of FSH, LH and testosterone in jugular blood plasma, of testosterone and oestradiol in testicular venous blood plasma and of testosterone in rete testis fluid in the hormone-treated hypophysectomized rams. The testes of the unheated hypophysectomized rams increased in size by about 20% during treatment with pituitary extract, although testicular blood plasma flow was lower per unit weight of testis. The absolute volume of each Leydig cell and the total volume in absolute terms and as a fraction of the interstitial tissue was greater in the hormone-treated than in the untreated rams, but not the volume as a fraction of the whole testis. The total number of Leydig cells was higher in the hormone-treated unheated rams than in all the other rams taken together.(ABSTRACT TRUNCATED AT 400 WORDS)

Nuclear testosterone receptors in the ovine testis.

Nuclear [3H] testosterone-receptor complexes were demonstrated in hypophysectomized ram testis after in vitro direct labelling. The nuclear binding was maximal after a 45 min incubation of the tissue. The receptors are extractable by 0.4 M KC1 or NaSCN with a 25-30% efficiency. They migrate towards the anodic region during electrophoresis on agar gel. Nuclear androgen receptors were characterized in intact lamb testis by a testosterone exchange assay. After precipitation by protamine sulphate, the receptors were labelled with [3H]testosterone during a 12 h incubation at 4 degrees C. The exchange activity was linear between 0.1 and 0.9 mg of DNA per ml of incubation buffer. The receptors bind testosterone with a limited capacity (40-180 fmoles per mg DNA) and a dissociation constant Kd of 2 x 10(-9) M. Their relative affinities for steroids are dihydrotestosterone greater than testosterone greater than estradiol greater than progesterone greater than 5 alpha-androstanediol greater than cyproterone acute greater than R5020.

Characterization of a cytoplasmic androgen receptor in the ram testis.

An androgen receptor has been characterized in the cytosol fraction of testes from hypophysectomized adult rams after in vitro labelling with [3H]testosterone. It can be distinguished from the testicular androgen-binding protein (ABP) and from the plasma 5 alpha-dihydrotestosterone-binding protein by electrophoresis on 3.25% acrylamide gels (Rx = 0.5) and on agar gels (anodic migration). It sediments in the 4S region in sucrose gradient containing 0.4 M KCl. Its complex with testosterone dissociates very slowly (t 1/2 = 29 h at 0 degrees C), and is destroyed by heating at 50 degrees C for 30 min and by pronase. Its relative affinities for steroids are 5 alpha-DHT greater than T greater than 5 alpha-androstanediols greater than cyproterone acetate greater than estradiol greater than progesterone. The number of binding sites is limited (about 20 fmoles/mg protein) and the apparent equilibrium dissociation constant (KD) is 5 x 10(-9) M.

Effects of experimental cryptorchidism and subsequent orchidopexy on seminiferous tubule functions in the lamb.

The reversibility of damage caused by cryptorchidism to the seminiferous tubules of the lamb was investigated at various ages. Lambs were made bilaterally cryptorchid either at birth or at 2 months of age. Then orchidopexy was performed at either 2 or 4 months of age. In permanently cryptorchid lambs, spermatogenesis stopped completely, and Sertoli cell function, as measured by FSH receptors, androgen receptors and ABP, was much reduced (-96%, -86% and -81%, respectively). Orchidopexy allowed the cryptorchid seminiferous epithelium to grow again, but the more differentiated the germ cells, the less they were capable of restoration. Even in 0- to 2- and 0- to 4-month-old temporarily cryptorchid lambs that had recovered normal Sertoli cell function, 16 to 49% of the tubules still were empty. It was concluded that cryptorchidism irreversibly damages the seminiferous tubules at a level other than the hormone receptors.

Endocrine parameters, hormone receptors, and functions of the testicular interstitium and seminiferous epithelium in estradiol-immunized Ile-de-France rams.

The testicular response of Ile-de-France rams actively immunized against estradiol (E2) was evaluated during both the ovine nonbreeding season (spring) and breeding season (autumn). Plasma concentrations of LH, FSH and testosterone were elevated in E2-immunized rams during both spring and autumn when compared with BSA-immunized controls. Testis weights were significantly elevated by E2 immunization and were characterized by greater interstitial cell volume, including Leydig cells, blood and lymph vessels, greater seminiferous tubule length, and greater numbers of leptotene spermatocytes and round spermatids. Neither Sertoli cell number, Sertoli cell nuclear volume nor testicular FSH receptor number were affected by E2 immunization, but testis weight, Sertoli cell nuclear area, FSH receptor number and LH receptor number were significantly greater in autumn than in spring. A positive effect of E2 immunization on testicular LH receptors was evident in spring but not in autumn. Testicular androgen receptors were suppressed by E2 immunization but were not affected by season. It was concluded that E2 immunization results in moderate stimulation of the ovine testis to increase testosterone secretion and to enhance total daily spermatid production. This effect appears to result from a change in E2 negative feedback and increased pituitary gonadotropin secretion.