Estrogen receptor alpha and beta expression in upper gastrointestinal tract with regulation of trefoil factor family 2 mRNA levels in ovariectomized rats

STUDY OBJECTIVE: To investigate the effect of short-term inhalation of nitric oxide (NO) on transpulmonary angiotensin II formation in patients with severe ARDS. DESIGN: Prospective, clinical study. SETTING: Anesthesiology ICU of a university hospital. PATIENTS: Ten ARDS patients who responded to inhalation of 100 ppm NO by decreasing their pulmonary vascular resistance (PVR) by at least 20 dyne x s x cm(-5) were included in the study. INTERVENTIONS AND MEASUREMENTS: In addition to standard treatment, the patients inhaled 0, 1, and 100 ppm NO in 20-min intervals. Fraction of inspired oxygen was 1.0. Hemodynamics were measured and recorded online. Mixed venous (pulmonary arterial catheter) and arterial (arterial catheter) blood samples were taken simultaneously for hormonal analyses at the end of each inhalation period. RESULTS: Pulmonary arterial pressure decreased from 33+/-2 mm Hg (0 ppm NO, mean+/-SEM) to 29+/-2 mm Hg (1 ppm NO, p<0.05), and to 27+/-2 mm Hg (100 ppm NO, p<0.05, vs 0 ppm). PVR decreased from 298+/-56 (0 ppm NO) to 243+/-45 dyne x s x cm(-5) (1 ppm NO, not significant [NS]), and to 197+/-34 dyne x s x cm(-5) (100 ppm NO, p<0.05, vs 0 ppm). Arterial oxygen pressure increased from 174+/-23 mm Hg (0 ppm NO) to 205+/-26 mm Hg (1 ppm NO, NS), and to 245+/-25 mm Hg (100 ppm NO, p <0.05, vs 0 ppm). Mean plasma angiotensin II concentrations were 85+/-20 (arterial) and 57+/-13 pg/mL (mixed venous) during 0 ppm NO and did not change during inhalation of 1 and 100 ppm NO. Mean transpulmonary plasma angiotensin II concentration gradient (=difference between arterial and mixed venous blood values) was 28+/-8 pg/mL (range, 0 to 69) during 0 ppm NO and did not change during inhalation of 1 and 100 ppm NO. Mean transpulmonary angiotensin II formation (transpulmonary angiotensin II gradient multiplied with the cardiac index) was 117+/-39 ng/min/m2 (range, 0 to 414) during 0 ppm NO and did not change during inhalation of 1 and 100 ppm NO. Mean arterial plasma cyclic guanosine monophosphate concentration was 11+/-2 pmol/mL (0 ppm NO), did not change during 1 ppm NO, and increased to 58+/-8 pmol/mL (100 ppm NO, p<0.05). Arterial plasma concentrations of aldosterone (142+/-47 pg/mL), atrial natriuretic peptide (114+/-34 pg/mL), angiotensin-converting enzyme (30+/-5 U/L), and plasma renin activity (94+/-26 ng/mL/h of angiotensin I) did not change. CONCLUSION: The decrease of PVR by short-term NO inhalation in ARDS patients was not accompanied by changes in transpulmonary angiotensin II formation. Our results do not support any relationship between transpulmonary angiotensin II formation and the decrease in PVR induced by inhaled NO.     

Responsiveness of the adult male rat reproductive tract to 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure: Ah receptor and ARNT expression, CYP1A1 induction, and Ah receptor down-regulation

Cardiovascular diseases (CVD), principally coronary heart disease (CHD), stroke, and congestive heart failure, continue to be the leading cause of death claiming nearly 1,000,000 lives annually and accounting for more than 40% of the deaths in the United States (American Heart Association). While cardiovascular disease is often viewed as a problem of the elderly, 45% of heart attacks occur among individuals less than 65 years old. Moreover, CVD is the second leading cause of death for those 45 to 64 years of age and the third leading cause of death for those 25 to 44 years old. In economic terms, the annual direct and indirect costs of heart attack and stroke are approximately $259 billion or $492,444/second, in the United States alone. Thus, from a human and economic perspective, heart and vascular diseases are an enormous burden worthy of significant attention. This review is not intended to ignore the 50% decline in age-adjusted rates for heart attack and stroke events over the preceding three decades, as summarized by the recent report of the Joint National Committee on the Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC VI). However, progress has halted as coronary heart disease and stroke mortality rates have reached a plateau in recent years and appear to be rising. Consequently, this is an excellent time for re-examining our approach to the prevention and treatment of CVD. In this article, readers will find an overview of the CVD prevention and treatment topics and not an in-depth analytical or epidemiological assessment of risk factors and outcomes. First, a macroscopic approach to reducing CVD is presented, followed by a discussion emphasizing the critical importance of public health and community-based programs in the effort to significantly reduce the burden of hypertension and related cardiovascular morbidity and mortality. Effective public health programs can play a pivotal role in raising awareness, and more importantly, in facilitating lifestyle change, entry and retention in the healthcare system, and compliance with non-pharmacological as well as drug therapy.     

Estrogen receptor expression in bovine and rat retinas

PURPOSE: To investigate the expression and distribution of estrogen receptor protein and mRNA in bovine and rat retinas. METHODS: Western blot analysis with an antiestrogen receptor monoclonal antibody (mAb) was used to detect estrogen receptor protein in the bovine retina. Immunohistochemistry with an antiestrogen receptor mAb and in situ hybridization with an oligodeoxynucleotide sequence coding for estrogen receptor were applied to study the cellular distribution of estrogen receptor protein and its mRNA in male bovine retina and rat retina of both sexes. RESULTS: Estrogen receptor protein was detected in bovine retina by Western blot analysis. Immunohistochemical staining with the antiestrogen receptor mAb was widespread throughout the neural retina. Specific staining showed extensive distribution localizing in the nerve fiber layer, the ganglion cell layer, the inner nuclear layer, and the outer plexiform layer. Retinal pigment epithelium and choroid were also stained with the antiestrogen receptor mAb. By in situ hybridization, the expression of estrogen receptor mRNA was predominantly observed in ganglion cell layer, the inner nuclear layer, and outer portion of the outer nuclear layer. No significant difference was found between male and female rats in the immunostaining of retinas with the antiestrogen receptor mAb. CONCLUSIONS: This study provides the first evidence for the presence of estrogen receptor in bovine and rat retinas. Expression of estrogen receptor throughout the retina suggests that estrogen may have important functions in the retina.     

Regulation of androgen and estrogen receptors in male excurrent ducts of the goat: an immunohistochemical study

Prosopo-thoracopagus twins are united from the face down to the umbilicus, none with union in the brain but all with visceral anomalies intermediate between those of cephalopagus and thoracopagus. In a review of over 1200 cases of conjoined twins reported during the past 100 years, there were 14 that illustrate the continuum between cephalopagus and thoracopagus, including three that were united only from the cervical region to the umbilicus. Classic cephalopagus twins are joined from the top of the head to the umbilicus, sharing a single foregut as well as two relatively normal hearts, the "posterior" one often diminished. Typical thoracopagus, however, are conjoined only from the upper thorax to the umbilicus, each twin with a normal foregut but both sharing a single complex multiventricular heart. The intermediate cases shared either a single very abnormal heart or two hearts united by double aortic arches, and all except one had a single foregut. It is these cases intermediate between cephalopagus and thoracopagus which are the subject of this report.     

Neoplasia of the male reproductive tract

Genital neoplasms in the male horse are relatively uncommon. Squamous cell carcinomas and squamous papillomas are the most commonly diagnosed neoplasms of the penis and prepuce. Geldings appear to be overrepresented for these types of neoplasms, and accumulation of smegma may be a contributing factor. Early diagnosis and treatment are essential for salvaging these organs before lesions become excessively large and invasive or are allowed to metastasize. Newer treatment modalities such as 5-fluorouracil appear to be promising alternatives to surgical excision. Although generally considered to be uncommon, testicular tumors may occur more frequently than previously thought and have the potential for devastating effects on stallion fertility. Cryptorchidism appears to play a role in the development of equine testicular tumors, especially teratomas. Seminoma is by far the most common testicular tumor of the mature stallion. Seminomas are rapidly growing tumors with a greater potential to metastasize in the horse than in other domestic species. Leydig cell and Sertoli cell tumors have been reported but are relatively rare in the stallion. Orchiectomy is the standard treatment for most testicular tumors. In certain circumstances, however, such as neoplasia occurring in the only functional testis, local cryotherapy of testicular tumors may prolong the breeding career of an affected stallion.     

Homing receptor alpha4beta7 integrin expression predicts digestive tract involvement in mantle cell lymphoma

Appropriate staging and evaluation of residual disease is critical to improving the treatment of patients with lymphoma. The specific expression of homing receptors may determine the preferential dissemination pattern of tumoral cells. We investigated the expression of the mucosal homing receptor alpha4beta7 on tumoral cells from peripheral lymph node in patients with newly diagnosed mantle cell lymphoma (MCL) to check whether it is associated with gastrointestinal involvement. Expression of the alpha4beta1 integrin and the peripheral lymph node addressin CD62L were also examined. Thirteen MCL patients presenting with peripheral lymphadenopathy were studied. Expression of the mucosal homing receptor integrin alpha4beta7 by peripheral lymph node lymphoma cells was found to be frequent (5/13) and associated with gastrointestinal involvement (5/7). In contrast, lymphoma cells from patients without gastrointestinal involvement did not express alpha4beta7 (6/6) (P = 0.03). These data suggest that alpha4beta7 integrin is expressed by a subset of MCLs and that its expression may predict digestive tract involvement in MCL, furnishing a basis for recognizing two distinct clinical and phenotypic forms, ie, "digestive homing (or digestive primitive)" versus "peripheral" MCL. Further studies on more patients will be needed to understand the impact of biological differences on the prognosis of these two clinical forms.     

Obstruction of the male reproductive tract

Anatomic obstruction of the male reproductive ducts may be congenital, inflammatory or iatrogenic in origin. Two cases of congenital obstruction and 1 case of iatrogenic obstruction are presented. Accurate identification of the etiology and location of the obstruction is necessary for patient counseling and choice of treatment.     

Immunocytochemical localization of progesterone receptor in the reproductive tract of adult female rats

The distribution of the progesterone receptor (PR) was investigated immunocytochemically in female reproductive tracts of rats during the estrous cycle and early pregnancy through use of an anti-PR monoclonal antibody. PR was localized predominantly in the nuclei of epithelial, stromal, and muscle cells in the uterus and vagina during the estrous cycle. In the uterus, the nuclei of epithelial cells were stained intensively at diestrus, while the PR staining of the stromal cells was more intense at proestrus than at any other stage of the cycle. PR expression during the cycle in muscle cells of the myometrium was similar to that in the endometrial stromal cells. In the vagina, however, PR expression during the cycle was approximately the same among epithelial, stromal, and muscle cells, the nuclei of which were stained deeply at proestrus. Ovariectomy at various stages of the cycle altered the PR expression appearing in the uterus and vagina during the cycle. In ovariectomized rats, estrogen increased the PR immunoreaction of various types of cells examined in the uterus and vagina except for the uterine epithelial cells. The reaction of these uterine epithelial cells was decreased by estrogen but was increased by progesterone given after estrogen; however, progesterone given alone reduced the reaction. In the epithelial and stromal cells of the uterus, intensity of the staining was increased after mating, reaching maximum on Day 3 of pregnancy, and then decreased on Day 4 (day of implantation), while in epithelial and stromal cells of the vagina the staining remained weak during early pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Anatomy and function of the reproductive tract in the captive male tree shrew (Tupaia belangeri)

The reproductive anatomy of the male tree shrew (Tupaia belangeri) was examined and compared with other Tupaiidae. The testes are located prepenially in a pigmented scrotum which is fused to the base of a pendulous penis. The terminal portion of the vas deferens is differentiated into an ampullary gland and joins the duct of the seminal vesicle to form a short ejaculatory duct. The prostate is a compact bilateral body drained by a main collecting duct. In the aggregate, these features indicate that the reproductive system in Tupaia is primate in character. Testicular function in tree shrews is affected by both social and seasonal factors. When males were housed communally, the majority exhibited testicular degeneration accompanied by a loss in the weight and fructose content of the seminal vesicles and in pigmentation of the scrotum. These changes may be due to the presence of dominant conspecifics since animals kept in isolation undergo normal sexual development. Animals captured throughout the year and isolated show seasonal fluctuations in androgenic and spermatogenic function. Reproductive capacity is maximal during the winter and minimal during the summer. Local environmental factors appear to regulate reproductive function so that the greatest number of births occur during the dry season.     

Postnatal changes of nicotinic acetylcholine receptor alpha 2, alpha 3, alpha 4, alpha 7 and beta 2 subunits genes expression in rat brain

We have previously demonstrated the development of acoustically reflective liposomes as a novel ultrasound contrast agent, that can be conjugated to antibodies for site specific acoustic enhancement of pathologically altered vascular tissue. The liposomes are echogenic due to the lipid composition, without gas entrapment, and have a size of less than one micron (Alkan-Onyuksel et al., 1996). When conjugated to anti-fibrinogen antibodies, the liposomes have the ability to attach to fibrin coated surfaces and thrombi in vitro as demonstrated by scanning electron microscopy and ultrasound imaging (Demos et al., 1997a). Anti-fibrinogen liposomes were shown to attach to fibrous atheroma and thrombi in a Yucatan miniswine model of induced atherosclerosis whereas liposomes conjugated to anti-intercellular adhesion molecule-1 (anti-ICAM-1) were demonstrated to target early stage atherosclerotic plaques (Demos et al., 1997b). The purpose of this study is to evaluate the binding characteristics of anti-fibrinogen liposomes in vitro under a variety of flow conditions in order to optimize the targeting ability of the immunoliposomes. Radiolabeled anti-fibrinogen liposomes were applied to fibrin coated filter paper and placed in a flow circuit under controlled flow conditions. Flow conditions were altered to study the effects of different shear stresses, temperature, plasma flow and pulsatile flow on the retention of liposomes to fibrin after set time periods. The retention of liposomes conjugated to polyclonal and monoclonal antibodies as well as Fab fragments made from monoclonal antibodies were compared. The binding characteristics of liposomes conjugated to different quantities of polyclonal antibodies were analyzed. At physiological shear stress of 1.5 N/m2 (15 dynes/cm2) over 70% of the liposomes remained attached to fibrin after two hours. A smaller and greater portion of the liposomes remained attached at higher and lower shear stresses respectively. Plasma components and temperature had no effect on liposomal retention whereas pulsatile flow resulted in a slight reduction in binding. Monoclonal antibodies showed a slight trend of reduced retention to fibrin over time as compared with polyclonal antibodies and Fab fragments. The quantity of antibody conjugated to the liposomes plays a role in liposome retention as demonstrated by the reduction in liposome retention caused by reducing the quantity of antibody conjugated to the liposomes. Anti-fibrinogen liposomes were retained to the fibrin surface to a large extent under all flow conditions likely to occur in vivo and therefore can provide site specific ultrasound contrast for a long enough time period to allow for imaging after injection.     

Estrogen receptor activation factor (E-RAF) of the rat uterus: hormonal control

Evidence is presented showing that the synthesis of the estrogen receptor activation factor (E-RAF) in the rat uterus is under both estrogenic and progestational control. An ELISA method for the measurement of E-RAF is described and used to measure the E-RAF titre in the pregnant rat uterus. It is proposed that E-RAF synthesis during pregnancy is under the exclusive control of progesterone.     

Location of a membrane-bound carbonic anhydrase isoenzyme (CA IV) in the human male reproductive tract

We studied the location of a membrane-bound carbonic anhydrase (CA IV) in the human male reproductive tract using a specific antiserum to human CA IV in conjunction with immunoblotting, immunoperoxidase, and immunofluorescence techniques. The microvilli and apical plasma membrane of the epithelial cells and the subepithelial smooth muscle layer of the epididymis, ductus deferens, and ampulla of the ductus deferens showed specific staining for CA IV. The epithelial cells of the prostate and seminal vesicle failed to stain for CA IV, however, whereas the subepithelial smooth muscle layer showed positive staining. No specific staining for CA II was seen in the epithelium of the epididymal duct or the proximal ductus deferens. The presence of CA IV in the epididymis was confirmed by immunoblotting, which revealed 35 KD and 33 KD polypeptides. The results show that the microvilli and the apical plasma membrane of the lining epithelium of the epididymal duct, ductus deferens, and ampulla of the ductus deferens contain the membrane-bound carbonic anhydrase isoenzyme IV. The presence of the enzyme in the epithelium of the epididymis and ductus deferens is probably linked to the acidification of the epididymal fluid that prevents premature sperm activation. Its physiological role in the smooth muscle cells remains to be elucidated.     

Follistatin and activin A production by the male reproductive tract

Follistatin is a binding protein for the activin and inhibin family of hormones, regulating their biological activity. In the male reproductive tract, the interaction of these factors is likely to be involved in the regulation of the proliferation of several cell types. We have investigated the presence of follistatin and activin A in seminal plasma using specific immunoassays and have localized follistatin and activin/inhibin subunits in the adult human testis, prostate and seminal vesicle to establish their likely sources. High concentrations of immunoreactive follistatin were present in seminal plasma in normal men (mean 97.9 ng/ml; 1.43 ng/ml in peripheral plasma) and were similar in men with oligo/azoospermia and following vasectomy. Follistatin immunoreactivity was localized to both Leydig and Sertoli cells of the testis, and to epithelial cells of the prostate gland and seminal vesicle, which are likely to be the predominant sources of the hormone in seminal plasma. Activin A was also present in seminal plasma in normal men but was undetectable following vasectomy, thus deriving from the testis. Consistent with this finding, the betaA-subunit was immunolocalized in Sertoli and Leydig cells but was not present in seminal vesicle or prostate gland. The functional significance of the high concentrations of follistatin secreted into seminal plasma by the prostate gland and/or seminal vesicle is uncertain, but they may regulate the biological activity of testis-derived activin A and inhibin B.     

Glucocorticoids increase retinoid-X receptor alpha (RXRalpha) expression and enhance thyroid hormone action in primary cultured rat hepatocytes

A dynamic model of glucose overflow metabolism in batch and fed-batch cultivations of Escherichia coli W3110 under fully aerobic conditions is presented. Simulation based on the model describes cell growth, respiration, and acetate formation as well as acetate reconsumption during batch cultures, the transition of batch to fed-batch culture, and fed-batch cultures. E. coli excreted acetate only when specific glucose uptake exceeded a critical rate corresponding to a maximum respiration rate. In batch cultures where the glucose uptake was unlimited, the overflow acetate made up to 9. 0 +/- 1.0% carbon/carbon of the glucose consumed. The applicability of the model to dynamic situations was tested by challenging the model with glucose and acetate pulses added during the fed-batch part of the cultures. In the presence of a glucose feed, E. coli utilized acetate 3 times faster than in the absence of glucose. The cells showed no significant difference in maximum specific uptake rate of endogenous acetate produced by glucose overflow and exogenous acetate added to the culture, the value being 0.12-0.18 g g-1 h-1 during the entire fed-batch culture period. Acetate inhibited the specific growth rate according to a noncompetitive model, with the inhibition constant (ki) being 9 g of acetate/L. This was due to the reduced rate of glucose uptake rather than the reduced yield of biomass.     

Clear cell neoplasms of the urinary tract and male reproductive system

Herein is a review of clear cell neoplasms of selected sites in the urinary tract and male reproductive system, including the kidney, the urinary bladder, testis, epididymis, and prostate. Clear cell cytoplasmic alteration in neoplasms at these sites is a relatively common light microscopic finding. Examples of such neoplasms with clear cell change include the clear cell type of renal cell carcinoma, clear cell adenocarcinoma of urethra and bladder, the classic type of seminoma, papillary cystadenoma of the epididymis, and well-differentiated adenocarcinoma of the prostate. Of importance, numerous non-neoplastic benign entities may also manifest cleared cytoplasm and therefore are presented in the differential in this review. Indeed, knowledge of the neoplastic and non-neoplastic entities displaying clear cell change at each anatomic site should enable the surgical pathologist to approach the differential diagnosis of these conditions in a more logical and rigorous fashion.