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Biomedical subjects

G A Johnson

Publications and source records attributed to G A Johnson.

At least 19 recordsLinked to original sources

Origin and ontogeny of mammalian ovarian neurons.

Mammalian ovaries contain sympathetic neurons expressing the low affinity neurotropin receptor (p75NTR). To date neither the role these neurons might play in ovarian physiology nor their embryological origin is known. Immunohistochemistry was used to detect postnatal changes in distribution and number of both p75NTR-positive and tyrosine hydroxylase-positive neurons in rhesus monkey ovaries. Pig fetuses were used to map the pathway of ovarian neuronal migration during embryonic development. Antiserum to p75NTR revealed the presence of isolated neurons and neurons clustered into ganglia in 2-month-old monkey ovaries. After 8 months, the neurons exhibited well-developed processes, and other than being more extensively interlaced, the localization and morphology did not change after 2 yr of age. Total number of p75NTR-positive neurons present decreased gradually between 2 months and 12 yr of age and declined markedly with reproductive aging. Conversely, the subpopulation of neurons immunoreactive to anti-tyrosine hydroxylase increased significantly at puberty and then declined with the loss of reproductive capacity. By d 21 of fetal life in the pig, p75NTR neurons had migrated medially from the neural crest to form the paraaortic autonomic ganglia. Some neurons migrated ventrally from the ganglia and then continued ventrolaterally to enter the genital ridge. By d 27, neurons had entered the developing ovary, and by d 35, the migration was complete with neurons demonstrating immunoreactivity to NeuN, a neuron-specific marker. Results demonstrate that p75NTR-expressing ovarian neurons originate from the neural crest and that a catecholaminergic subset is associated with pubertal maturation of the ovary and subsequent reproductive function.

Age Factors↗

Maternal recognition of pregnancy signal or endocrine disruptor: the two faces of oestrogen during establishment of pregnancy in the pig.

Timing of conceptus growth and attachment to the uterine luminal epithelium is regulated by progesterone secretion from the corpus luteum and by expression of progesterone receptor in the uterine epithelia and stroma. Conceptus growth and uterine attachment are temporally associated with the disappearance of progesterone receptors from uterine epithelia. While the loss of progesterone receptor from the endometrial epithelia on day 10 of the oestrous cycle and pregnancy has been well documented, the factors involved with cell specific down-regulation of progesterone receptor are yet to be established. We propose that several progesterone stimulated factors activate nuclear factor kappa B (NF-kB) within the uterine epithelia, which leads to inhibition of progesterone receptor and concomitant stimulation of endometrial genes expressed during early conceptus development. Although oestrogens secreted by pig conceptuses function to establish pregnancy, timing of endometrial exposure to oestrogen is critical. Early oestrogen administration alters the pattern of gene expression through the NF-kB system desynchronising the uterine environment for conceptus implantation resulting in later embryonic loss.

Animals↗

Reproductive cytotoxicity is predicted by magnetic resonance microscopy and confirmed by ubiquitin-proteasome immunohistochemistry in a theophylline-induced model of rat testicular and epididymal toxicity.

This study investigated the testicular changes in the rat induced by the nonspecific phosphodiesterase inhibitor, theophylline using magnetic resonance microscopy (MRM) and ubiquitin immunostaining techniques. In vivo T1- and T2-weighted images were acquired at 2 T under anesthesia. Increased signal observed in the theophylline-treated rats suggests that leakage of MRM contrast was occurring. In vivo MRM results indicate that day 16 testis displayed an increased T1-weighted water signal in the area of the seminiferous tubule that decreased by day 32. These findings were validated by histopathology, suggesting that in vivo MRM has the sensitivity to predict changes in testis and epididymal tissues. The participation of the ubiquitin system was investigated, using probes for various markers of the ubiquitin-proteasome pathway. MRM can be used to detect subtle changes in the vascular perfusion of organ systems, and the up-regulation/mobilization of ubiquitin-proteasome pathway may be one of the mechanisms used in theophylline-treated epididymis to remove damaged cells before storage in the cauda epididymis. The combined use of in vivo MRM and subsequent tissue or seminal analysis for the presence of ubiquitin in longitudinal studies may become an important biomarker for assessing testis toxicities drug studies.

Animals↗

Temporal and spatial associations of oestrogen receptor alpha and progesterone receptor in the endometrium of cyclic and early pregnant mares.

Uterine function is primarily controlled by the combined actions of oestrogen and progesterone working through their cognate nuclear receptors. The mechanism of establishment of pregnancy in the mare is of interest because it involves prolonged pre-attachment and conceptus migration phases, and both invasive and non-invasive placental cell types, and as such has been an important comparative model. This study characterised regulation of oestrogen (ER) and progesterone (PR) receptors in the endometrium of the mare during the oestrous cycle and early pregnancy. Endometrial tissues collected during the oestrous cycle and early pregnancy were analysed for steady-state levels of ER and PR mRNA and protein. Steady-state levels of ER and PR mRNA were highest on days 0, 17 and 20 in cyclic mares and lowest on days 11 and 14. A day-by-status interaction was detected, indicating that day 17 and day 20 pregnant mares exhibited low levels of ER and PR compared with the corresponding days of the oestrous cycle. In situ hybridisation analyses showed receptor mRNA localisation primarily in the luminal epithelium (LE), glandular epithelium (GE) and stroma around oestrus. During dioestrus and early pregnancy, receptors were not detected in the LE, and were lower in the stroma and deeper GE. Changes in hybridisation intensity in these cell types were consistent with changes in mRNA levels detected by slot-blot hybridisation. ER and PR proteins were detected in the nuclei of LE, GE and stromal cells. Consistent with results from in situ hybridisation, levels of ER and PR immunoreactivity were higher around oestrus, declined to low levels during dioestrus and remained low during early pregnancy. Results described here for temporal and spatial changes in steroid receptor gene expression in mares show the greatest similarities with those described for cattle and sheep.

Animals↗

Conceptus signals for establishment and maintenance of pregnancy.

Establishment and maintenance of pregnancy results from signaling by the conceptus (embryo/fetus and associated extraembryonic membranes) and requires progesterone produced by the corpus luteum. In most mammals, hormones produced by the trophoblast maintain progesterone production by acting directly or indirectly to maintain the corpus luteum. In domestic animals (ruminants and pigs), hormones from the trophoblast are antiluteolytic in that they act on the endometrium to prevent uterine release of luteolytic prostaglandin F2alpha. In cyclic and pregnant sheep, progesterone negatively autoregulates progesterone receptor gene expression in the endometrial luminal and superficial glandular epithelium. In cyclic sheep, loss of the progesterone receptor is closely followed by increases in epithelial estrogen receptors and then oxytocin receptors, allowing oxytocin to induce uterine release of luteolytic prostaglandin F2alpha pulses. In pregnant sheep, the conceptus trophoblast produces interferon tau that acts on the endometrium to inhibit transcription of the estrogen receptor alpha gene directly and the oxytocin receptor gene indirectly to abrogate development of the endometrial luteolytic mechanism. Subsequently, sequential, overlapping actions of progesterone, interferon tau, placental lactogen, and growth hormone comprise a hormonal servomechanism that regulates endometrial gland morphogenesis and terminal differentiated function to maintain pregnancy in sheep. In pigs, the conceptus trophoblast produces estrogen that alters the direction of prostaglandin F2alpha secretion from an endocrine to exocrine direction, thereby sequestering luteolytic prostaglandin F2alpha within the uterine lumen. Conceptus estrogen also increases expression of fibroblast growth factor 7 in the endometrial lumenal epithelium that, in turn, stimulates proliferation and differentiated functions of the trophectoderm, which expresses the fibroblast growth factor 7 receptor. Strategic manipulation of these physiological mechanisms may improve uterine capacity, conceptus survival, and reproductive health.

Animals↗

Micro-CT with respiratory and cardiac gating.

Cardiopulmonary imaging in rodents using micro-computed tomography (CT) is a challenging task due to both cardiac and pulmonary motion and the limited fluence rate available from micro-focus x-ray tubes of most commercial systems. Successful imaging in the mouse requires recognition of both the spatial and temporal scales and their impact on the required fluence rate. Smaller voxels require an increase in the total number of photons (integrated fluence) used in the reconstructed image for constant signal-to-noise ratio. The faster heart rates require shorter exposures to minimize cardiac motion blur imposing even higher demands on the fluence rate. We describe a system with fixed tube/detector and with a rotating specimen. A large focal spot x-ray tube capable of producing high fluence rates with short exposure times was used. The geometry is optimized to match focal spot blur with detector pitch and the resolution limits imposed by the reproducibility of gating. Thus, it is possible to achieve isotropic spatial resolution of 100 microm with a fluence rate at the detector 250 times that of a conventional cone beam micro-CT system with rotating detector and microfocal x-ray tube. Motion is minimized for any single projection with 10 ms exposures that are synchronized to both cardiac and breathing motion. System performance was validated in vivo by studies of the cardiopulmonary structures in C57BL/6 mice, demonstrating the value of motion integration with a bright x-ray source.

Animals↗

Expression of the uterine Mx protein in cyclic and pregnant cows, gilts, and mares.

Pregnancy and interferon-tau (IFN tau) upregulate uterine Mx gene expression in ewes; however, the only known role for Mx is in the immune response to viral infection. We hypothesize that Mx functions as a conceptus-induced component of the anti-luteolytic mechanism and/or regulator of endometrial secretion or uterine remodeling during early pregnancy. This study was conducted to determine the effects of early pregnancy on uterine Mx expression in domestic farm species with varied mechanisms of pregnancy recognition. Endometrium from cows, gilts, and mares was collected during the first 20 d of the estrous cycle or pregnancy, and total messenger RNA (mRNA) and protein were analyzed for steady-state levels of Mx mRNA and protein. Northern blot analysis of Mx mRNA detected an approximately 2.5 Kb of mRNA in endometrium from each species. In pregnant cows, steady-state levels of Mx mRNA increased 10-fold (P < 0.05) above levels observed in cyclic cows by d 15 to 18. In cyclic gilts, slot blot analysis indicated that endometrial Mx mRNA levels did not change between d 5 and 18 of the cycle. However, in pregnant gilts, Mx levels tended (P = 0.06) to be elevated two-fold on d 16 only, and in situ hybridization indicated that this increase occurred in the stroma. In mares, Mx mRNA was low, but detectable, and did not change between ovulation (d 0) and d 20, regardless of reproductive status. Western blot analysis revealed multiple immunoreactive Mx protein bands in each species. One band was specific to pregnancy in cows. As in ewes, in situ hybridization analysis indicated that Mx mRNA was strongly expressed in the luminal epithelium, stroma, and myometrium by d 18 in cows. However, on d 14 in gilts, Mx was expressed primarily in the stroma, and on d 14 in mares, low levels of Mx expression were confined largely to the luminal epithelium. The uteruses of cows, gilts, and mares express Mx, and expression is upregulated during pregnancy in cows and gilts--animals whose conceptuses secrete interferons during early pregnancy, but that possess different mechanisms for pregnancy recognition.

Animals↗

Postpartum uterine involution in sheep: histoarchitecture and changes in endometrial gene expression.

After parturition, the uterus undergoes marked remodelling during involution; however, little is known of the hormonal, cellular and molecular mechanisms that regulate this process. The working hypothesis used in this study is that return of the ovine uterus to a non-pregnant state involves termination of a hormonal servomechanism that regulates endometrial gland morphogenesis and function during pregnancy. Suffolk ewes were ovariohysterectomized on postpartum days 1, 7, 14 or 28. Serum concentrations of oestradiol were high at parturition, declined to postpartum day 4, peaked on postpartum day 6, and then declined and remained low thereafter. Progesterone was undetectable in plasma from ewes post partum. Uterine wet mass and horn length decreased after postpartum day 1, but ovarian mass did not change. Residual placental cotyledons were present in the maternal caruncles on postpartum days 1 and 7 and were extruded by postpartum day 14 as plaques that were resorbed by postpartum day 28. The width of the total endometrium, stratum compactum, stratum spongiosum and myometrium, as well as endometrial gland density, decreased after parturition. Most apoptotic cells in the involuting uterus were large, vacuolated and located between the endometrial glandular epithelial cells on postpartum days 1 and 7. Immunofluorescence analyses identified both T and B cells within the glandular epithelium on postpartum day 1. Cell proliferation was detected in the luminal epithelium and glandular epithelium on postpartum days 1 and 7. On postpartum day 1, expression of oestrogen receptor alpha (ERalpha) was not detected in luminal epithelium and was low in glandular epithelium, but ERalpha was present in epithelia thereafter. Progesterone receptor (PR) protein was not detected in endometrial epithelia on postpartum day 1, but was detected in the glandular epithelium thereafter. Between postpartum days 1 and 7, ERalpha and PR protein increased substantially in the endometrial glandular epithelium. On postpartum days 1-28, abundant expression of oxytocin receptor mRNA was detected in endometrial luminal epithelium and superficial to the middle glandular epithelium. Prolactin receptor (PRLR) mRNA was detected in glandular epithelium on all postpartum days, whereas mRNA for uterine milk protein (UTMP), an index of secretory capacity of glandular epithelium, was present only on postpartum day 1. Collectively, these results indicate that uterine involution in ewes involves remodelling of both caruncular and intercaruncular areas of the uterine wall and termination of differentiated uterine gland functions characteristic of pregnancy.

Animals↗

Application of magnetic resonance microscopy to tissue engineering: a polylactide model.

Absorbable polymers are unique materials that find application as temporary scaffolds in tissue engineering. They are often extremely sensitive to histological processing and, for this reason, studying fragile, tissue-engineered constructs before implantation can be quite difficult. This research investigates the use of noninvasive imaging using magnetic resonance microscopy (MRM) as a tool to enhance the assessment of these cellular constructs. A series of cellular, polylactide constructs was developed and analyzed using a battery of tests, including MRM. Distribution of rat aortic smooth muscle cells within the scaffolds was compared as one example of a tissue engineering MRM application. Cells were loaded in varying amounts using static and dynamic methods. It was found that the cellular component was readily identified and the polymer microstructure readily assessed. Specifically, the MRM results showed a heterogeneous distribution of cells due to static loading and a homogenous distribution associated with dynamic loading, results that were not visible through biochemical tests, scanning electron microscopy, or histological evaluation independently. MRM also allowed differentiation between different levels of cellular loading. The current state of MRM is such that it is extremely useful in the refinement of polymer processing and cell seeding methods. This method has the potential, with technological advances, to be of future use in the characterization of cell-polymer interactions.

Absorbable Implants↗

The Interferon Stimulated Genes (ISG) 17 and Mx have different temporal and spatial expression in the ovine uterus suggesting more complex regulation of the Mx gene.

Interferon stimulated gene 17 (ISG17) and Mx are up-regulated in the ruminant uterus in response to interferon-tau (IFNtau) during early pregnancy. Recent evidence strongly indicates that expression of ISGs occur only in stroma (ST) and glandular epithelium (GE) during this time as a result of transcriptional repression by interferon regulatory factor two (IRF-2) expression in the LE. The present report tested this hypothesis by examining mRNA and protein expression of ISG17 and Mx in serial uterine cross-sections obtained from cyclic and early pregnant ewes. In situ and immunocytochemical analysis revealed that ISG17 mRNA and protein were low to undetectable, whereas Mx mRNA was expressed in the lumenal (LE) and superficial GE at all days of the estrous cycle examined. Both ISG17 and Mx mRNA increased in the stratum compactum ST between Days 11 and 13, and expression extended into the deep GE and stratum spongiosum ST on Days 15 through 17 in pregnant ewes. Interestingly the Mx gene continued to be strongly expressed in LE and superficial GE through Day 17 of pregnancy, whereas ISG17 remained low to undetectable in these cells. Collectively, this study highlights the complexity of the uterine environment by unequivocally illustrating differential temporal and spatial expression of the IFN-responsive genes ISG17 and Mx.

Animals↗

Evidence that absence of endometrial gland secretions in uterine gland knockout ewes compromises conceptus survival and elongation.

Endometrial glands are necessary for conceptus implantation and growth. In the ovine uterine gland knockout (UGKO) model, blastocysts hatch normally but fail to survive or elongate. This peri-implantation defect in UGKO ewes may be due to the absence of endometrial glands or, alternatively, to the lack of certain epithelial adhesion molecules or the inability of the endometrium to respond to signals from the conceptus. Two studies were performed to examine these hypotheses. In study one, normal (n = 8) and UGKO (n = 12) ewes were mated at oestrus (day 0) with intact rams and their uteri were flushed 14 days after oestrus. Normal ewes (n = 4) were also flushed on 14 days after oestrus. Uterine flushes from bred normal ewes contained filamentous conceptuses (n = 7 of 8), whereas those from UGKO ewes contained no conceptus (n = 5 of 12), a growth-retarded, tubular conceptus (n = 6 of 12), or a fragmented, filamentous conceptus (n = 1 of 12). In all groups, expression of mucin 1 and integrin alpha(v), alpha(5), beta(3) and beta(5) was localized at the apical surface of the endometrial luminal epithelium with no detectable differences between normal and UGKO ewes. Uterine flushes from pregnant ewes, but not cyclic or UGKO ewes, contained abundant immunoreactive interferon tau and the cell adhesion proteins, osteopontin and glycosylation-dependent cell adhesion molecule one. In study two, UGKO ewes were fitted with uterine catheters 5 days after oestrus, infused with recombinant ovine interferon tau or control proteins from 11 to 15 days after oestrus, and underwent hysterectomy 16 days after oestrus. Expression of several interferon tau-stimulated genes (ISG17, STAT1, STAT2 and IRF-1) was increased in the endometrium from interferon tau-infused UGKO ewes. These results support the hypothesis that the defects in conceptus elongation and survival in UGKO ewes are due to the absence of endometrial glands and their secretions rather than to alterations in expression of anti-adhesive or adhesive molecules on the endometrial luminal epithelium or to the responsiveness of the endometrium to the conceptus pregnancy recognition signal.

Animals↗

Registered (1)H and (3)He magnetic resonance microscopy of the lung.

Using in vivo magnetic resonance microscopy, registered (1)H and hyperpolarized (3)He images of the rat lung were obtained with a resolution of 0.098 x 0.098 x 0.469 mm (4.5 x 10(-3) mm(3)). The requisite stability and SNR was achieved through an integration of scan-synchronous ventilation, dual-frequency RF coils, anisotropic projection encoding, and variable RF excitation. The total acquisition time was 21 min for the (3)He images and 64 min for the (1)H image. Airways down to the 6th and 7th orders are clearly visible. Magn Reson Med 45:365-370, 2001.

Animals↗

Measurements of hyperpolarized gas properties in the lung. Part III: (3)He T(1).

Hyperpolarized (3)He spin-lattice relaxation was investigated in the guinea pig lung using spectroscopy and imaging techniques with a repetitive RF pulse series. T(1) was dominated by interactions with oxygen and was used to measure the alveolar O(2) partial pressure. In animals ventilated with a mixture of 79% (3)He and 21% O(2), T(1) dropped from 19.6 sec in vivo to 14.6 sec after cardiac arrest, reflecting the termination of the intrapulmonary gas exchange. The initial difference in oxygen concentration between inspired and alveolar air, and the temporal decay during apnea were related to functional parameters. Estimates of oxygen uptake were 29 +/- 11 mL min(-1) kg(-1) under normoxic conditions, and 9.0 +/- 2.0 mL min(-1) kg(-1) under hypoxic conditions. Cardiac output was estimated to be 400 +/- 160 mL min(-1) kg(-1). The functional residual capacity derived from spirometric magnetic resonance experiments varied with body mass between 5.4 +/- 0.3 mL and 10.7 +/- 1.1 mL. Magn Reson Med 45:421-430, 2001.

Animals↗

Laparoscopic pelvic and paraaortic lymph node dissection: analysis of the first 100 cases.

OBJECTIVE: The aim of this study was to analyze the first 100 cases of planned laparoscopic pelvic and paraaortic lymph node dissection (LND) done for staging of gynecologic cancers. The goal of the study was to assess prognostic factors for conversion to laparotomy and document complications. METHODS: A retrospective review of patients who had planned laparoscopic bilateral pelvic and bilateral paraaortic LND for staging of their gynecologic cancer was performed. Patients were identified by our institutional database and data were collected by review of their medical records. Data were obtained regarding demographics, stage, histology, length of stay, and procedural information including completion rates, operating room time, estimated blood loss, assistant, lymph node count, and complications. Associations between variables were analyzed using Student t tests, analysis of variance, and chi(2) testing (Excel v7.0). RESULTS: A total of 103 patients were identified from 12/15/95 to 8/28/00. Demographics included mean age of 66.2 (25-92) and mean Quetelet index (QI) of 30.8 (15.9-56.1). A total of 34/103 (33.0%) had > or =1 previous laparotomy. Ninety-five patients had endometrial cancer and 8 had ovarian cancer. Eighty-six of 103 (83.5%) were stage I or II. The length of stay was shorter for those who had laparoscopy than for those who needed conversion to laparotomy (2.8 vs 5.6 days, P < 0.0001). Laparoscopy was completed in 73/103 (70.9%) of the cases. Completion rates were 62/76 (81.6%) with QI < 35 vs 11/27 (40.7%) with QI > or = 35, P < 0.001. Significantly more patients had their laparoscopy completed when an attending gynecologic oncologist was the first assistant compared to a fellow or a community obstetrician/gynecologist (92.9%, 69.0%, 64.5%, P < 0.0001). The top three reasons for conversion to laparotomy were obesity, 12/30 (29.1%), adhesions, 5/30 (16.7%), and intraperitoneal disease, 5/30 (16.7%). Pelvic, common iliac, and paraaortic lymph node counts did not differ when compared to those of patients who had conversion to laparotomy (18.1, 5.1, 6.8 vs 17.3, 5.7, 6.8, P = ns). Complications included 2 urinary tract injuries, 2 pulmonary embolisms, and 6 wound infections (all in the laparotomy group). Two deaths occurred, 1 due to a vascular injury on initial trocar insertion and 1 due to a pulmonary embolism after a laparotomy for bowel herniation through a trocar incision. CONCLUSION: Laparoscopic bilateral pelvic and paraaortic LND can be completed successfully in 70.9% of patients. Age, obesity, previous surgery, and the need to perform this procedure in the community were not contraindications. Advantages include a shorter hospital stay, similar nodal counts, and acceptable complications.

Adult↗

Surgical management of early-stage endometrial cancer in the elderly: is laparoscopy feasible?

OBJECTIVE: To give insight into the utility of laparoscopic staging of endometrial cancer in the elderly population by reviewing the surgical management of clinically stage I endometrial cancer patients. METHODS: A retrospective analysis evaluating patients that were > or =65 years old and had planned laparoscopic staging, traditional staging via a laparotomy, or a transvaginal hysterectomy as management of their early endometrial cancer. The laparoscopic group had complete staging with bilateral pelvic and paraaortic lymph node dissections and was compared to the group who had staging performed via laparotomy. Patients were identified by our institution's database and data were collected by review of their medical records. Data were collected on demographics, pathology, and procedural information including completion rates, operating room (OR) time, estimated blood loss (EBL), transfusions, lymph node count, complications, and length of stay. Associations between variables were analyzed by Student's t tests and chi(2) testing using Excel v. 9.0. RESULTS: From February 25, 1994, through December 21, 2000, 125 elderly patients were identified. Sixty-seven patients had planned laparoscopic staging (Group 1), 45 patients had staging via planned laparotomy (Group 2), and 13 patients had a transvaginal hysterectomy (Group 3). Group 1 and Group 2 were compared regarding surgical and postoperative data. Age was not different between these groups (75.9 vs 74.7 years, P = NS). Quetelet index was also similar (29.4 vs 29.9, P = NS) 32.8% of Group 1 had > or =1 previous laparotomy compared to 51.1% in Group 2 (P = NS). In Group 1, 53/67 (79.1%) had stage I or II disease compared to 29/45 (64.4%) in Group 2 (P = NS). Laparoscopy was completed in 52/67 (77.6%) attempted procedures. The reasons for conversion to laparotomy were obesity 7/67 (10.4%), bleeding 4/67 (6.0%), intraperitoneal cancer 3/67 (4.5%), and adhesions 1/67 (1.5%). OR time was significantly longer in successful Group 1 patients compared to Group 2 patients (236 vs 148 min, p = 0.0001). EBL was similar between these groups (298 vs 336 ml, P = NS). Ten of 52 (19.2%) of successful Group 1 patients received a blood transfusion compared to 1/45 (2.2%) of Group 2 patients (P < 0.0001). Pelvic, common iliac, and paraaortic lymph node counts were similar between successful Group 1 patients and those in Group 2 combined with those that received a laparotomy in Group 1 (17.8, 5.2, 6.6 vs 19.1, 5.1, 5.2, P = NS). Length of stay (LOS) was significantly shorter in Group 1 versus Group 2 (3.0 vs 5.8 days, P < 0.0001). There were less fevers (6.0 vs 15.6%, P = 0.01), less postoperative ileus's (0 vs 15.6%, P < 0.001), and less wound complications (6.0 vs 26.7%, P = 0.002) in Group 1 compared to Group 2. Group 3 average age was 77.5 years. Concurrent medical comorbidities were the main reason for the transvaginal approach. OR time averaged 104.5 min. The average length of stay was 2.1 days with no procedural or postoperative complications. CONCLUSIONS: The favorable results from this retrospective study refute the bias that age is a relative contraindication to laparoscopic surgery. Laparoscopic staging was associated with an increased OR time and an increased rate of transfusion but equivalent blood loss and lymph node counts. Possible advantages are decreased length of stay, less postoperative ileus, and less infections complications. Transvaginal hysterectomy still remains a proven option for women with serious comorbid medical problems with short OR times, minimal complications, and short lengths of stay.

Aged↗

Bovine interferon-tau stimulates the Janus kinase-signal transducer and activator of transcription pathway in bovine endometrial epithelial cells.

Trophoblastic bovine interferon-tau (bIFN-tau) suppresses luteolytic pulses of endometrial prostaglandin F(2alpha) (PGF(2alpha)) at the time of maternal recognition of pregnancy. This results in maintenance of the corpus luteum in cattle. The hypothesis that effects of bIFN-tau in the endometrium were through activation of the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway of signal transduction was tested. Whole cell, cytosolic, and nuclear extracts from bovine endometrial cells treated with bIFN-tau were analyzed by immunoprecipitation, immunoblotting, and electrophoretic mobility shift assays in a series of dose- and time-dependency experiments. Bovine IFN-tau stimulated tyrosine phosphorylation, homo- and heterodimer formation, nuclear translocation, and DNA binding of STAT proteins 1, 2, and 3. Moreover, bIFN-tau induced synthesis of interferon-regulatory factor. In conclusion, bIFN-tau stimulates the JAK-STAT pathway in the bovine endometrium. It is proposed that activation of the JAK-STAT pathway is involved in regulating the antiluteolytic effects of bIFN-tau.

Animals↗

Monocyte chemotactic protein-1 and -2 messenger ribonucleic acids in the ovine uterus: regulation by pregnancy, progesterone, and interferon-tau.

Endometrial leukocytes may play important roles during pregnancy. Because chemokines are regulators of immune cell activity and trafficking, this study determined if mRNAs for monocyte chemotactic proteins (MCP) were present in the ovine uterus and regulated by progesterone (P) and/or recombinant ovine interferon tau (roIFN-tau). Uteri of normal cycling and pregnant ewes (experiment 1) and uteri of ovariectomized ewes receiving intrauterine infusions of IFN-tau and/or i.m. injections of P (experiment 2) were used to detect MCP-1 and MCP-2 mRNA. In experiment 1, slot-blot hybridization analysis of endometrial total RNA revealed that MCP-1 and MCP-2 mRNA levels did not change during the estrous cycle but increased between Days 13 and 19 of pregnancy. Using in situ hybridization, MCP-1 and MCP-2 mRNA were localized to immune cells in the subepithelial compact stroma. Histomorphological studies and in situ hybridization for major basic protein (MBP) indicated that MCP-positive immune cells were eosinophils. In experiment 2, treatment with P and roIFN-tau increased (P < 0.05) the number of MCP-1- and MCP-2-expressing eosinophils in the endometrium compared to ewes treated with P alone. Injection of the P receptor antagonist (ZK 137,316) inhibited effects of P and/or roIFN-tau to recruit eosinophils expressing MCP-1 and MCP-2 mRNAs. Endometrial production of MCPs by eosinophils during early pregnancy may play a role(s) in central implantation and/or placentation in ewes that is crucial for successful establishment of pregnancy.

Animals↗