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PubMed1983

The renin-angiotensin system in panhypopituitarism: dynamic studies and therapeutic effects in Sheehan's syndrome.

To gain insight in the influence of the pituitary gland on the renin-angiotensin system plasma renin substrate (PRS) and the response of PRA to stimulation were studied in a homogeneous group of 20 female patients with the same etiology and degree of pituitary failure, before treatment (group P), after hydrocortisone substitution (group F), and after hydrocortisone and thyroid hormone treatment (group F + T). All patients were studied before and after each treatment by response to two stimulatory tests, acting through two different pathways; orthostasis test (O-T) and the furosemide test (Furo-T). Results were compared between groups, each patient serving as her own control, and with those obtained in a 12 healthy women control group (group C). The diet contained about 85 meq Na/day. Compared to group C (O-T response, 5.97 +/- 0.54 ng ml-1 h-1; Furo-T response, 6.71 +/- 0.82 ng ml-1 h-1; mean +/- SEM), PRA response to both tests was blunted in group P (O-T: 2.48 +/- 0.46, P less than 0.001; Furo-T: 3.02 +/- 0.53, P less than 0.001) and remained so in F (O-T: 2.18 +/- 0.40, P less than 0.001; Furo-T: 2.52 +/- 0.28, P less than 0.001), In group F + T, the response to both tests was greater than in P and F (O-T, 6.61 +/- 1.19; Furo-T, 4.36 +/- 0.44; 0.001 less than P less than 0.05). However, whereas the response to orthostasis is entirely normalized, the response to a diuretic remained significantly smaller than in group C (P less than 0.01). These improvements were observed without significant change in PRS concentration which remained low. We conclude that panhypopituitarism is accompanied by an altered renin angiotensin system. Basal levels of PRS and PRA are low and unresponsive to adequate stimulation. Whereas glucocorticoid therapy alone is without effect on this hyporeninism, addition of thyroid hormones completely normalized the response to orthostasis and significantly improved furosemide response.

Adult↗
PubMed1984

The monodeiodination of triiodothyronine and reverse triiodothyronine in man: a quantitative evaluation of the pathway by the use of turnover rate techniques.

These studies were performed to evaluate the quantitative role of monodeiodination in the peripheral metabolism of T3 and rT3 in man. As a prerequisite step, the serum concentrations of two diiodothyronines (T2s), 3,5-T2 and 3',5'-T2, were established by specific RIAs. In 20 normal subjects, mean (+/- SEM) serum concentrations of 3,5-T2 and 3',5'-T2 were 0.40 +/- 0.18 and 2.07 +/- 0.13 ng/dl, respectively. The mean concentrations of both T2s were significantly increased in hyperthyroidism. In primary hypothyroidism, the mean 3,5-T2 concentration was not significantly different from normal, but 3',5'-T2 concentrations were undetectable in the majority of subjects. In the first experiments, the MCRs of rT3 and all three T2s were derived by the constant infusion method. Seven normal subjects were infused simultaneously with the three 125I-labeled T2s for 12 h, and in four of the subjects, [131I]rT3 was also administered. The MCRs (liters/day . 70 kg; mean +/- SEM) were: rT3, 130 +/- 17; 3,5-T2, 168 +/- 15; 3,3'-T2, 621 +/- 84; and 3',5'-T2, 305 +/- 45. The daily production rates (PR; micrograms per day/70 kg; mean +/- SEM) were: rT3, 29.1 +/- 1.0; 3,5-T2, 0.6 +/- 0.1; 3,3'-T2, 20.8 +/- 4.1; and 3',5'-T2, 5.7 +/- 2.1. In the four subjects who received [131I]rT3, the serum T2 concentrations and PRs were also derived by turnover rate techniques. At equilibrium, 2.0 +/- 0.7% and 6.0 +/- 1.6% of [131I] rT3 were found as [131I]3,3'-T2 and [131I]3',5'-T2, respectively. The serum T2 concentrations were derived by the product of these percentages and the serum rT3 concentrations and compared with those obtained by T2 RIA. The serum 3',5'-T2 concentration was 1.3 +/- 0.4 ng/dl (tracer), and its PR was 3.4 +/- 1.1 micrograms/day (tracer); these values were closely correlated with those obtained by RIA. Serum 3,3'-T2 concentrations were 0.4 +/- 0.2 ng/dl (tracer) and 2.7 +/- 0.4 ng/dl (RIA), and the PRs were 3.2 +/- 1.6 micrograms/day (tracer) and 20.3 +/- 5.7 micrograms/day (RIA), indicating that rT3 5'-deiodination contributes only a small proportion of serum 3,3'-T2 and its PR. An analysis of the rT3 PR and the 3,3'-T2 and 3',5'-T2 PRs derived from the turnover of rT3 revealed that 28% of the rT3 produced was degraded by monodeiodination. Of this total, 49% of the deiodination occurred at the 5' position and 51% occurred at the 5 position.(ABSTRACT TRUNCATED AT 400 WORDS)

Chemical Precipitation↗
PubMed2003

Mitogen-activated protein kinase regulates nuclear association of human progesterone receptors.

Breast cancers often have increased MAPK activity; this pathway may drive breast cancer cell growth by targeting steroid hormone receptors. MAPK phosphorylates human progesterone receptors (PRs) on Ser294, thus regulating several aspects of PR activity. To study the role of PR Ser294 phosphorylation on subcellular distribution, we stably expressed wild-type (wt) or S294A (Ser294 to Ala) PR-B in several cell types. PRs phosphorylated on Ser294 were nuclear. Activation of MAPK induced Ser294 phosphorylation and rapid nuclear translocation of wt, but not S294A, PR-B; both receptors concentrated in the nucleus after progestin treatment. The MAPK kinase inhibitor, U0126, blocked epidermal growth factor but not progestin-induced Ser294 phosphorylation and translocation of wt PR, indicating a novel mechanism for nuclear localization. After progestin treatment, wt PR-B underwent ligand-dependent down-regulation, while S294A PR-B persisted in nuclei. Prolonged treatment with U0126 or the nuclear export inhibitor, leptomycin B, promoted nuclear accumulation of wt PR-B and blocked ligand-dependent PR down-regulation, suggesting that PR degradation occurs in the cytoplasm and requires MAPK-dependent nuclear export. Stabilization of PRs by leptomycin B also blocked PR transcriptional activity, indicating a link between nucleocytoplasmic shuttling, receptor stability, and function. These results support a regulatory role for MAPK in nuclear steroid hormone receptor subcellular localization and coupling to multiple PR functions.

Acetylcysteine↗
PubMed1996

Dopamine requires the unoccupied progesterone receptor to induce sexual behavior in mice.

Using the recently generated mutant mice strain (PRKO) carrying a null mutation for the progesterone receptor (PR) gene by gene targeting, we examined the critical role of PR as a coordinator of key regulatory events involved in the steroid hormone and dopamine-facilitated sexual behavior in female mice. In vitro one-point binding analyses of estradiol benzoate (EB)-induced cellular PRs and immunohistochemistry of PR in the mediobasal hypothalamus demonstrated a reduction in binding in the homozygous females, equivalent to background levels seen in EB-unresponsive tissue. The biochemical findings correlated well with the behavioral observations, with the wild type females exhibiting high levels of lordosis, while the homozygous females showed minimal lordosis in response to mating by male mice. As a critical validation of our earlier studies on ligand-independent activation of PRs by dopamine, we examined the facilitation of sexual behavior by a dopamine agonist in the null mutants. Wild type females having the full complement of PRs exhibited high levels of lordosis, while the homozygous females showed minimal lordosis in response to dopamine. To determine whether this reduced response was due to a general lack of ability to express lordosis, mice were treated with another neurotransmitter, serotonin. No significant difference in the serotonin-facilitated lordosis response was observed between the wild type and the homozygous females. We conclude that multiple signal transduction pathways coexist in the neuroendocrine system for reproductive behavior, with PR acting as a transcriptional mediator for dopamine, as well as progesterone, to achieve integration of neural communication in the central nervous system.

Animals↗
PubMed1995

An Ets site in the whey acidic protein gene promoter mediates transcriptional activation in the mammary gland of pregnant mice but is dispensable during lactation.

The whey acidic protein (WAP) gene is specifically expressed in mammary tissue, and its transcription is induced several thousand-fold during pregnancy and remains high throughout lactation. A purine-rich sequence (PRS) located around -110 of the WAP gene promoter is conserved between mice, rats, and rabbits, suggesting that it features a regulatory element. This PRS contains an invariant GGAA/T core motif characteristic of the binding site for Ets transcription factors. Electromobility shift assays demonstrate that Ets1 binds specifically to the PRS. Experiments in transgenic mice further demonstrate that this PRS/Ets site plays a critical role in the activation of WAP transgenes during pregnancy, but that its presence is not required for high expression throughout lactation. Transgenes with an intact PRS/Ets site are expressed at high levels at day 13 of pregnancy, with little further increase during late pregnancy and lactation. In contrast, WAP transgenes with a mutation in the PRS/Ets site, which abrogates the binding of Ets1, are not expressed at midpregnancy, but their transcriptional activity is not affected during lactation. These results demonstrate that Ets-signaling pathways can function as stage-specific transcriptional activators of milk protein genes in the developing mammary gland. In addition, this work extends earlier findings that gene activation during pregnancy and lactation is mediated, in part, by different mechanisms.

Animals↗
PubMed2004

The maize duplicate genes narrow sheath1 and narrow sheath2 encode a conserved homeobox gene function in a lateral domain of shoot apical meristems.

The narrow sheath (ns) phenotype of maize is a duplicate factor trait conferred by mutations at the unlinked loci ns1 and ns2. Recessive mutations at each locus together confer the phenotypic deletion of a lateral compartment in maize leaves and leaf homologs. Previous analyses revealed that the mediolateral axis of maize leaves is comprised of at least two distinct compartments, and suggest a model whereby NS function is required to recruit leaf founder cells from a lateral compartment of maize meristems. Genomic clones of two maize homeodomain-encoding genes were isolated by homology to the WUSCHEL-related gene PRESSED FLOWER (PRS). PRS is required for lateral sepal development in Arabidopsis, although no leaf phenotype is reported. Co-segregation of the ns phenotype with multiple mutant alleles of two maize PRS homologs confirms their allelism to ns1 and ns2. Analyses of NS protein accumulation verify that the ns-R mutations are null alleles. ns transcripts are detected in two lateral foci within maize meristems, and in the margins of lateral organ primordia. Whereas ns1 and ns2 transcripts accumulate to equivalent levels in shoot meristems of vegetative seedlings, ns2 transcripts predominate in female inflorescences. Previously undiscovered phenotypes in the pressed flower mutant support a model whereby the morphology of eudicot leaves and monocot grass leaves has evolved via the differential elaboration of upper versus lower leaf zones. A model implicating an evolutionarily conserved NS/PRS function during recruitment of organ founder cells from a lateral domain of plant meristems is discussed.

Amino Acid Sequence↗
PubMed2004

Elongated styloid process: when is it really elongated?

OBJECTIVE: The styloid process (SP) is often denoted as elongated when it is longer than 30 mm or 33 mm. These dimensions, based on early reports, do not respect the natural variation of the SP. The aim of this study is to investigate the natural variation of the length of the SP. Knowing this variation is a prerequisite for consistent terminology in anatomy and anthropology; it is essential for the classification of the SP as elongated on panoramic radiographs (PRs). MATERIALS AND METHODS: 1000 consecutive PRs of a normal population were retrieved from inactive files at the Dental School of the Hannover Medical University. Measurements of the length of the SPs were made directly on the radiographs from the caudal margin of the tympanic plate to the tip of the SP. RESULTS: On 521 of the 1000 PRs the length of the SP could be measured at least on one side. As there was no significant difference between distributions on the left and right side, both sides were combined to give a total of 837 measurements. The median was 28.0 mm, the interquartile range was from 23.0 mm to 36.0 mm. The distribution depends significantly on age and gender. The 90th percentile varies between 42 mm for women under 35 years and 49 mm for men aged over 35 years. CONCLUSIONS: The medians in our sample correspond to the thresholds for elongated SP quoted in the literature. Our results show that these thresholds are too low, since they are exceeded in 50% of normal patients. We propose that the SP should be considered to be elongated only if its length exceeds 45 mm, which corresponds to the average of the 90th percentiles for different sex and age groups.

Adult↗
PubMed1995

Airway obstruction in the Pierre Robin sequence.

Airway obstruction and feeding difficulties vary among patients with Pierre Robin sequence (PRS). Treatment is challenging and the appropriate management may not be readily identified, leading to delay in securing the airway. A retrospective review of 90 children with PRS was done to identify subgroups at a higher risk of developing severe airway obstruction using oxygen and apnea monitoring, sleep studies, and response to treatment. Patients with isolated PRS (group I, 27 patients) and Stickler syndrome (group II, 32 patients) do not suffer from debilitating airway and feeding difficulties when compared to those with unique syndromes (group III, 16 patients) and recognized named syndromes (group IV, 15 patients). Feeding difficulties were universal with the severity proportional to airway obstruction. Aggressive intervention should be considered early in group III and IV patients.

Abnormalities, Multiple↗
PubMed1984

Renin-angiotensin system in hypothyroid rats: effects of potassium iodide and triiodo-L-thyronine.

Kinetic studies of the renin-angiotensin system (RAS) were carried out by measuring plasma renin activity (PRA), plasma renin concentration (PRC) and plasma renin substrate (PRS). Changes in this system were studied during hypothyroidism, after administration of propylthiouracil (PTU), and in thyroidectomized rats. A significant decrease in PRA and PRC was observed in those animals previously treated with PTU. However, a significant increase in PRC, and a decrease in PRS, were found in T animals, but no changes in PRA were observed. In these animals, after daily administration of potassium iodide for 1 week (T + KI), no changes in RAS were observed in comparison with T rats. Nevertheless, administration of daily doses of triiodo-L-thyronine (T + T3) induced a significant increase in PRA, leaving PRC unaltered. In this case the changes in PRA were related to the increase in PRS after T3 treatment. These results suggest that two different mechanisms were involved in renin release, one activated in T rats and the other in pharmacological hypothyroidism.

Animals↗
PubMed1982

Effects of the uterus and mid-pregnancy conceptus on luteal lifespan of the rat.

Hysterectomy on or after Day 10 resulted in a quick return of pseudopregnant rats to oestrus but the interval to oestrus in pregnant rats was significantly longer (P less than 0.01), indicating that the gravid uterine horn interfered with uterine-induced luteolysis by Day 10. When pseudopregnant rats were injected with extracts of conceptuses or pregnant rat serum (PRS), samples collected on Days 10 or 12 of pregnancy delayed the return to oestrus (P less than 0.01 for conceptus extracts, P less than 0.05 for PRS) and serum progesterone concentrations on Day 13 of pseudopregnancy were higher (P less than 0.01) than in controls. Bioassays utilizing mammary development or inhibition of oestrus in virgin cyclic rats as endpoints failed to detect lactogenic activity in Day 10 conceptus extracts or PRS, and radioreceptor assays using bovine prolactin (NIH-B5) as a standard showed that Day 10 extracts had only about 2--3% of the lactogenic activity found in Day 12 extracts. Injections of dilutions of Day 12 extracts with 2 or 4 times the lactogenic activity as Day 10 extracts did not extend pseudopregnancy. These results suggest that by Day 10 the conceptus produces a factor capable of interfering with luteolysis and that this factor is not placental lactogen.

Animals↗
PubMed2001

Increased risk for developmental disabilities in children who have major birth defects: a population-based study.

OBJECTIVE: We sought to quantify the strength of associations between each of four specific developmental disabilities (DDs) and specific types of major birth defects. METHODS: We linked data from 2 independent surveillance systems, the Metropolitan Atlanta Congenital Defects Program and the Metropolitan Atlanta Developmental Disabilities Surveillance Program. Children with major birth defects (n = 9142; born 1981-1991 in metro Atlanta) and 3- to 10-year-old children who were born between 1981 and 1991 in metro Atlanta and identified between 1991 and 1994 as having mental retardation, cerebral palsy, hearing impairment, or vision impairment (n = 3685) were studied. Prevalence ratio (PR), which is the prevalence of a DD in children with 1 or more major birth defects divided by the prevalence of the same DD in children without major birth defects, was measured. RESULTS: Among the 9142 children who were born with a major birth defect, 657 (7.2%) had a serious DD compared with 0.9% in children with no major birth defect, yielding a PR of 8.3 (95% confidence interval: 7.6-9.0). In general, the more severe the DD, the higher was the PR. Birth defects that originated in the nervous system and chromosomal defects resulted in the highest PRs for a subsequent DD. For all other categories of birth defects, PRs were lowest when all major birth defects present were confined to a single category (ie, isolated defects). PRs for any DD increased monotonically with the number of coded birth defects per child or the number of different birth defect categories per child, regardless of the severity of the defect or whether defects of the nervous system, chromosomal defects, or "other syndromes" were counted. CONCLUSIONS: These data highlight the possible early prenatal origins of some DDs and suggest that both the number of coded birth defects present and the number of anatomic systems involved are strongly related to functional outcomes.

Abnormalities, Multiple↗
PubMed1997

Evaluation of the results of cleft lip and palate surgical treatment: preliminary report.

OBJECTIVE: The aim of this study was to present a measuring tool, in the form of a dual-rating grid, for preoperative appearance and postoperative results in the treatment of labionasal clefts. METHODS: This study was carried out on 43 children with partial unilateral clefts, operated on using a derivation of Millard's technique. The preoperative initial severity score (ISS) was the sum of points each corresponding to a precise anatomic anomaly. A severe cleft was given a rating of 6, and a mild cleft a rating of 1. The postoperative results score (PRS) was the sum of points corresponding to residual or acquired anatomic anomalies: a good result was given 0.5, and a poor result 3.5. Each score was a mark given separately and agreed on by two surgeons. To compare the rating grids, the correlation between the ISS and the PRS was calculated. RESULTS: Twenty-four patients had an ISS less than 5; 19 patients had an IGS more than or equal to 5. Marks for the PRS were between 0.5 and 3.5 with the majority at 1 to 1.5. CONCLUSION: This study demonstrates the coherent connection between these two pre- and postoperative rating grids.

Cleft Lip↗
PubMed2003

Management of infants with Pierre Robin sequence.

OBJECTIVE: Several methods of treating babies with Pierre Robin sequence have been described since the condition itself was first documented in 1923. The main aim of treatment has been to relieve upper airway obstruction. Treatment methods used range from positioning of the baby to invasive surgery. The aim of this article was to describe the assessment, treatment, and monitoring methods used for babies referred with Pierre Robin sequence (PRS). SETTING/PATIENTS: From December 1995 to May 2000, 22 consecutive patients were admitted to Birmingham Children's Hospital with PRS. Their airway and nutritional status were assessed and continuously monitored. INTERVENTIONS: Treatment concentrated on the relief of airway obstruction with a nasopharyngeal airway (NPA) and nutritional support of the babies until they grew out of their respiratory and feeding difficulties. MAIN OUTCOME MEASURES: Outcome measures were oxygen saturation, growth of the babies, and the need for surgery. RESULTS: All babies were managed successfully with an NPA and nutritional support. No baby required surgery, and the majority showed good weight gain. CONCLUSION: Relieving airway obstruction by NPA is an effective and safe treatment for babies with PRS until they have grown out of their respiratory and feeding difficulties. It avoids the need for surgery and can be used on neonatal wards using the monitoring described.

Airway Obstruction↗
PubMed1999

Lessons from the use of aromatase inhibitors in the neoadjuvant setting.

Postmenopausal patients with oestrogen receptor-positive locally advanced T4b, N0-1, M0 and large operable breast cancers T2>3 cm, T3, T4, N0-1 and M0 have been treated with 2.5 mg letrozole (12 patients), 10 mg letrozole (12 patients), 1 or 10 mg anastrozole (24 patients) and 20 mg tamoxifen (65 patients). There was no apparent difference in response rate between 2.5 and 10 mg letrozole. Only 17 patients with anastrozole have so far completed the 3-month treatment period. Median clinical, mammographic and ultrasound reductions in tumour volumes for patients treated with letrozole were 81% (95% confidence interval (CI) 66-88), 77% (95% CI 64-82) and 81% (95% CI 69-86) respectively and for anastrozole, values were 87% (95% CI 59-97), 73% (95% CI 58-82) and 64% (95% CI 52-76) respectively. This compares with a median reduction in tumour volume for tamoxifen-treated patients as assessed by ultrasound of 48% (95% CI 27-48). There were seven complete clinical responses (CR), sixteen patients who achieved 50% or greater reduction in tumour volume (PR) and one no change (NC) for letrozole and four CRs, twelve PRs and one progressive disease for anastrozole. Best radiological responses were one CR, twenty PRs and three NCs for letrozole and one CR, fifteen PRs and one NC for anastrozole. This study has shown that the new aromatase inhibitors, letrozole and anastrozole, are highly effective agents in the neoadjuvant setting and they should now be compared with tamoxifen as first-line treatment in a randomised study.

Aged↗
PubMed1994

Immunohistochemical localization of intracellular progesterone and glucocorticoid receptors in the rabbit lung.

We have determined the presence and distribution of intracellular progesterone receptors (PRs) and glucocorticoid receptors (GRs) in the lung of adult female rabbits using immunohistochemistry. The effects of ovariectomy and administration of oestradiol benzoate (10 micrograms for 3 consecutive days) upon PR and GR immunoreactivity were also studied. The results demonstrated the presence of both steroid hormone receptors in the female rabbit lung. PR and GR immunoreactivity was predominantly nuclear and located in alveolar epithelial cells and various interstitial cells such as polymorphonuclear leucocytes. Tissue distribution of both receptors was similar in all cases. Oestradiol treatment induced a marked increase in the number of PR immunoreactive cells compared with intact and ovariectomized female animals. Neither ovariectomy nor oestradiol treatment modified the number of GR immunoreactive cells. The presence and localization of intracellular PRs and GRs in several lung cell types suggest that they may play an important role in mediating the effects of progesterone and glucocorticoids in various physiological processes in the rabbit lung. The data also indicated an oestrogen regulation of PRs in the rabbit lung.

Animals↗
PubMed2006

Bone marrow stromal cells of young and adult rats respond similarly to platelet-released supernatant and bone morphogenetic protein-6 in vitro.

BACKGROUND: Age-related changes in periodontal bone regeneration, osseointegration of dental implants, and graft consolidation are increasingly considered in treatment planning. This study was intended to show whether aging is associated with a diminished responsiveness of osteoprogenitor cells to growth and differentiation factors. METHODS: We compared the capacity of bone marrow stromal cells harvested from young and adult rats to proliferate, migrate, and differentiate into the osteogenic lineage following exposure to platelet-released supernatant (PRS) or bone morphogenetic protein-6 (BMP-6). Bone marrow stromal cells were isolated from 12 young rats aged 6 weeks and 12 adult rats aged 9 months. Proliferation was assessed by 3[H]thymidine incorporation, migration was evaluated with the Boyden chamber assay, and osteogenic differentiation was deduced from alkaline phosphatase activity. RESULTS: Irrespective of the donor age, bone marrow stromal cells showed increased mitogenic activity and chemotactic motility when exposed to PRS. Adult bone marrow stromal cells had higher alkaline phosphatase activities at baseline and upon incubation with BMP-6 than cells obtained from young animals. There was no difference between the two groups in the slope of the alkaline phosphatase activity curve following stimulation with BMP-6. CONCLUSIONS: The data demonstrate that, irrespective of their age, bone marrow stromal cells respond similarly to PRS and BMP-6 under in vitro conditions. These findings suggest that osteoprogenitor cells within the bone marrow of adult rats retain their juvenile potential to respond to growth and differentiation factors, which are released naturally or are applied therapeutically at sites of bone regeneration.

Aging↗
PubMed2026

Partitioned blood pressure polygenic risk reveals differential genetic effects of tissue-specific enhancers and their interactions on cardiovascular disease.

Polygenic risk scores (PRS) compress genome-wide associations into a single predictor, but this aggregation obscures the distinct biological mechanisms through which genetic variation shapes complex traits. Here we introduce a framework that additively decomposes a trait's PRS, without loss of SNP heritability, into independent components defined by the tissue-specific and tissue-agnostic cis-regulatory elements (CREs) in which its variants act. Applied to blood pressure (BP) using ~0.5 million CREs across four BP-relevant tissues (adrenal gland, artery, heart, kidney), the framework reveals that regulatory effects are globally additive across tissues yet locally non-additive, and that the resulting partitioned scores carry pronounced, reproducible heterogeneity in their effects on BP and cardiovascular outcomes. We show this heterogeneity reflects gene-environment interactions, and trace one example to its mechanism: a kidney-CRE-partitioned score is protective against coronary artery disease and myocardial infarction through an interaction between ATP2B1 and antihypertensive medication. Explicitly modeling these interactions improves prediction and transferability, and tissue-focused partitioning increases power to resolve causal genes and reveals genes such as ADAMTS8 with antagonistic effects across BP components. Validated in an independent All of Us cohort, these findings recast the PRS from a blunt aggregate predictor into a mechanistic probe of context-dependent genetic architecture.

Journal Article↗
PubMed1989

Rapid growth of a meningioma during pregnancy: relationship with estrogen and progesterone receptors--case report.

Meningiomas are often described as hormone-dependent because of their preponderance in females and their tendency to clinically manifest during or after pregnancy. We describe a case of meningioma that grew rapidly during two pregnancies over a 2-year period. The tumor's rapid growth was confirmed by high-resolution computed tomography. Its estimated doubling time was 110 days. The tumor was removed and found to be a benign meningothelial meningioma. The tumor tissue was positive for estrogen receptors (ERs) and progesterone receptors (PRs). In nine cases, including this one, in which ERs and PRs were measured, the positive rate was much higher for PRs than for ERs; only two were positive for ERs. In the case reported here, it is presumed that the growth of the meningioma was influenced by estrogen and/or progesterone binding to receptors, although it is unclear whether one or both hormones was involved.

Adult↗