Hybridization studies of cultured human pituitary prl and gh producing adenoma cells: Effects of thyrotropin-releasing hormone,somatostatin, and phorbol ester

The effects of the hypothalamic hormones, thyrotropin-releasing hormone (TRH), and somatostatin (SRIH), and of phorbol 12-myristate 13-acetate (PMA) on PRL and GH secretion and messenger RNA (mRNA) levels were analyzed in 10 GH and/or PRL producing adenomas after culturing the tumor cells in the presence of these secretagogues for 7 days. The expression of chromogranin A and B mRNAs was also examined. All four of the clinically diagnosed GH adenomas expressed or secreted both GH and PRL while four of six clinically diagnosed prolactinomas produced or secreted both PRL and GH. Prolactinomas had less than 10% of tumor cells expressing chromogranin A mRNA while more than 40% of the adenoma cells expressed chromogranin B mRNA. TRH stimulated PRL secretion and increased PRL mRNA levels while SRIH decreased GH secretion and mRNA expression in some cases. Unexpectedly, PMA stimulated PRL mRNA levels four- to sevenfold above control levels in two adenomas and generally stimulated chromogranin A and B mRNA expression but not GH mRNA, as determined by Northern hybridization and in situ hybridization analyses. These results indicate that cultured prolactinoma cells express significantly more chromogranin B mRNA than chromogranin A mRNA, and that PMA increases PRL mRNA expression in some prolactinomas, although the effect of PMA on various adenomas reflects the heterogeneity of these tumors with respect to protein kinase C stimulation.     

Spontaneous nystagmus and gaze-holding ability in monkeys after intravitreal picrotoxin injections.

1. Eye movements were measured in three rhesus monkeys after monocular intravitreal injections of picrotoxin, a gamma-aminobutyric acid (GABA) antagonist. The effects of this drug were tested when the animals were in a completely dark room, when they performed a smooth pursuit task, and when they viewed either a stationary pattern or a full-field optokinetic pattern rotating horizontally. 2. Between 15 and 20 min after the injection, a sustained conjugate spontaneous nystagmus developed in the dark, with the slow-phase movement in the temporal-to-nasal direction with respect to the injected eye. Peak slow-phase velocity ranged from 15 to 45 degrees/s. The nystagmus persisted for at least 1 h but stopped by the next day. 3. In a well-lit room, the nystagmus was completely suppressed, even during monocular viewing with the injected eye. When the lights were turned off, the slow-phase velocity of the spontaneous nystagmus slowly increased to a steady-state level within 70-120 s. 4. Horizontal smooth pursuit eye movements to a 1 degree target light moving in front of the animal +/- 20 degrees to either side of center of gaze at constant speeds were normal. Target speeds ranging from 15 to 60 degrees/s for both monocular and binocular viewing conditions were used. Binocular and monocular optokinetic nystagmus (OKN) to a full-field drum rotating at a constant velocity (5-90 degrees/s) were also normal. The initial pursuit and steady-state components of OKN were measured, as well as the velocity-storage component (optokinetic after nystagmus, OKAN).(ABSTRACT TRUNCATED AT 250 WORDS)     

Orally administered myelin basic protein in neonates primes for immune responses and enhances experimental autoimmune encephalomyelitis in adult animals

Antigen-driven tolerance is an effective method for suppression of autoimmune diseases. Adult animals can be tolerized against the induction of experimental autoimmune encephalomyelitis (EAE) by both oral and parenteral administration of myelin basic protein (MBP). We have found that in contrast to previous studies of neonatal tolerance in which parenterally administered autoantigens induced tolerance, the oral administration of MBP in neonatal rats did not result in tolerization to MBP, but instead, primed for immunologic responses. Proliferative responses to MBP and its encephalitogenic epitope were present in animals fed with MBP as neonates and co-culture of encephalitogenic T cells with cells from neonatal rats fed with MBP were associated with enhanced MBP responses rather than the suppression observed with cells from adult rats fed with MBP. Furthermore, neonates fed with MBP and immunized 6–8 weeks later with MBP in adjuvant to induce EAE revealed enhancement of disease severity, and were not protected from a second attack upon active reinduction of EAE. Subcutaneous injection of soluble MBP into neonates had no effect on EAE induction as adults, whereas intraperitoneal injection of MBP in neonates was associated with marked suppression of disease in adults. Suppression of EAE began to appear in animals fed with MBP at 4 weeks of age, and was similar to oral tolerance in adult animals when animals were fed at 6 weeks of age. These results suggest that immaturity of the immunoregulatory network associated with oral tolerance and sensitization to autoantigens via the gut in the neonatal period may contribute to the pathogenesis of autoimmune diseases.     

Endothelial nitric oxide synthase immunoreactivity in early gestation and in trophoblastic disease.

AIMS: To study the localisation of the endothelial nitric oxide synthase (eNOS) in the normal placenta, with special emphasis on the implantation site in the first trimester of pregnancy, and in the different subtypes of trophoblastic cells in gestational trophoblastic disease. METHODS: The immunoperoxidase technique with an antibody directed against eNOS was applied to paraffin sections from first and second trimester placentas, placenta accreta, partial and complete hydatidiform moles, and choriocarcinoma. Immunoperoxidase staining for human placental lactogen (hPL) was performed on parallel sections. RESULTS: Prominent immunoreactivity for eNOS was found to be present in the intermediate trophoblastic cells of the cell columns of the anchoring villi and in trophoblastic cells at the implantation site. Staining was also present in the syncytiotrophoblast, most conspicuous at the apical cell border. In trophoblastic disease, proliferating large mononuclear cells, which were strongly positive for hPL, were found to be immunoreactive for eNOS. CONCLUSIONS: eNOS immunoreactivity is strongly positive in the extravillous trophoblastic cells and to a lesser extent in the syncytiotrophoblast. In the former it may play a role in implantation and vascular invasion. Cells with differentiation to intermediate trophoblast in complete hydatidiform mole and choriocarcinoma also show high levels of eNOS, which may be associated with the haematogenous mode of spread of trophoblastic disease.     

Impact of COVID‐19 on access to healthcare in low‐ and middle‐income countries: Current evidence and future recommendations

The COVID‐19 pandemic continues to be a major public health threat globally and low‐ and middle‐income countries (LMICs) are not an exception. The impact of the COVID‐19 pandemic is far‐reaching on many areas including but not limited to global health security, economic and healthcare delivery with a potential impact on access to healthcare in LMICs. We evaluate the impact of the COVID‐19 pandemic on access to healthcare in LMICs, as well as plausible strategies that can be put in place to ensure that the delivery of healthcare is not halted. In order to mitigate the devastating effect of the COVID‐19 pandemic on the already weak health systems in LMICs, it is much necessary to reinforce and scale up interventions and proactive measures that will ensure that access to healthcare is not disrupted even in course of the pandemic.     

Biofluid Aspects of Embryo Transfer

Embryo transfer (ET) is the last stage of extracorporal fertilization during which the embryo is placed in the uterine cavity with a medium-filled catheter 2–3 days after in vitro fertilization. While fertilization in the laboratory occurs at very high rates (>:90%), the overall success of the procedure (i.e., take home baby) is still very low (<25%) and assumed to be mainly due to implantation failure. A computational model was developed to simulate ET within the uterine cavity by a fluid-filled catheter inserted into a two-dimensional channel with oscillating walls. The results showed that the speed at which the embryos are injected from the catheter dominates the procedure and controls the velocity of their transport within the uterine cavity. ET at excessively high injection speeds may lead to ectopic pregnancies, while uterine peristalsis affects transverse dispersion only during injection at low injection speeds. The presence of the catheter within the uterus does not affect flow patterns downstream of its tip. The potential risks to implantation failure due to mechanical factors involved in the ET processes are discussed. © 2003 Biomedical Engineering Society. PAC2003: 8719-j, 8710+e     

Induction of follicular growth and production of a normal hormonal milieu in spite of using a constant low dose of luteinizing hormone in women with hypogonadotrophic hypogonadism

This study was designed to examine ovarian performance, i.e.follicular growth, normal steroidogenesis and luteal phase function,following the administration of multiple increasing doses ofhuman follicle stimulating hormone (FSH) with a constant lowdose of luteinizing hormone (LH) in women with isolated hypogonadotrophichypogonadism. Human meno–pausal gonadotrophin (HMG) wasused in the first treatment cycle, starting with 150 IU of LHand 150 IU of FSH per day, for 7 days. The dose was increaseddaily with 75 IU of LH and 75 IU of FSH for another 7 days ifno response was detected by serial ultrasound measurements andserumoestradiol determinations. In the second treatment cycle,a constant dose of 75 IU of LH (using HMG) was administeredper day and up to 150 IU of FSH (using urofollitrophin) wassupplemented. If no response was detected after 7 days of treatment,the dose of FSH was increased. For the final stage of ovulationinduction, human chorionic gonadotrophin (HCG) was administeredin the presence of at least one follicle >17 mm in diameterbut with no more than three follicles >16mm in diameter.To verify the adequacy of the luteal phase, a pharmacokinetic/pharmacodynamicstudy of -HCG, oestradiol and progesterone was performed followingthe second treatment cycle only. Ovarian stimulation using aconstant dose of 75 IU of LH and increasing doses of FSH upto 225 IU, resulted in normal follicular growth and hormonalmilieu. Both women showed normal luteal phase oestradiol andprogesterone production and both women conceived following thesecond treatment cycle     

Pyogenic liver abscess: Warning indicator of silent colonic cancer

PURPOSE: Carcinoma of the colon, manifested clinically as an enterococcal hepatic abscess, in the absence of liver metastases, is very uncommon. However, having treated a patient with such a condition, we would like to draw the attention of surgeons to this possibility. Most reports describe secondary infections of hepatic metastases only in patients with a known malignancy. However, increased awareness of colonic cancer as an underlying cause of pyogenic liver abscesses will afford earlier diagnosis and treatment. METHODS: The case was analyzed for history, presentation, laboratory data, radiologic studies, and bacteriology. RESULTS: A 66-year-old woman presented with abdominal pain, fever, and chills. Imaging scans revealed a solitary liver abscess, which was successfully treated with percutaneous drainage and broad-spectrum intravenous antibiotics. Pus cultures grew Streptococcus faecalis.A search for the underlying cause led to the discovery of an adenocarcinoma of the sigmoid colon. CONCLUSIONS: An aggressive search for the underlying cause of pyogenic liver abscesses should be an integral part of the definitive treatment of this disease. After prevailing etiologies have been excluded, silent colonic cancer should be considered.     

Quality of evidence matters: is it well reported and interpreted in infertility journals?

Journal of Assisted Reproduction and Genetics - To evaluate if the authors of published systematic reviews (SRs) reported the level of quality of evidence (QoE) in the top 5 impact factor...