A multicenter study of transient global amnesia for the better detection of magnetic resonance imaging abnormalities.

BACKGROUND AND PURPOSE: The detection rate of diffusion-weighted (DWI) hyperintense lesions varies widely in patients with transient global amnesia (TGA). The aim was to examine the association of hyperintense lesions on DWI magnetic resonance imaging (MRI) with patient characteristics, precipitating factors, clinical presentation and MRI settings in patients with TGA. METHODS: In this multicenter retrospective observational study, using the standardized diagnosis entry system of electronic health records of four tertiary medical centers in the Kansai district of Japan, TGA patients (n = 261) who underwent brain MRI within 28 days of onset were examined. When the onset time was unavailable, the discovery time was used. RESULTS: Diffusion-weighted hyperintense lesions were observed in 79 patients (30%). There were no significant differences in age, sex, vascular risk factors, precipitating factors or clinical presentation between patients with and without DWI lesions. The detection rate increased linearly 24 h after onset and then reached a plateau of 60%-80% by 84 h. After 84 h, the detection rate decreased rapidly. In a multivariate logistic regression model, MRI examination 24-84 h after onset (odds ratio 7.00, 95% confidence interval 3.50-13.99) and a thin-slice (≤3 mm) DWI sequence (odds ratio 7.59, 95% confidence interval 3.05-18.88) were independent predictors of DWI lesions. CONCLUSIONS: This study suggests that DWI hyperintense lesions in TGA are not associated with patient characteristics and clinical presentation. Brain MRI examination 24-84 h after onset and thin-slice DWI sequences enhance the detection of DWI lesions in TGA patients.

Impacts of climate change on snow accumulation and melting processes over mountainous regions in Northern California during the 21st century.

A point-location-based analysis of future climate change impacts on snow accumulation and melting processes was conducted over three study watersheds in Northern California during a 90-year future period by means of snow regime projections. The snow regime projections were obtained by means of a physically-based snow model with dynamically downscaled future climate projections. Then, atmospheric and snow-related variables, and their interrelations during the 21st century were investigated to reveal future climate change impacts on snow accumulation and melting processes. The analysis shows large reductions in snow water equivalent (SWE), snowfall to precipitation (S/P) ratio, and snowmelt through the 21st century. Timing of the peak of the SWE and snowmelt will also change in the future. Meanwhile, the analysis in this study shows that air temperature rise will affect, but will not dominate the future change in snowmelt over the study watersheds. This result implies the importance of considering atmospheric variables other than air temperature, such as precipitation, shortwave radiation, relative humidity, and wind speed even if these variables will not clearly change during the 21st century.

Analysis of future climate change impacts on snow distribution over mountainous watersheds in Northern California by means of a physically-based snow distribution model.

The impacts of climate change on snow distribution through the 21st century were investigated over three mountainous watersheds in Northern California by means of a physically-based snow distribution model. The future climate conditions during a 90-year future period from water year 2010 to 2100 were obtained from 13 future climate projection realizations from two GCMs (ECHAM5 and CCSM3) based on four SRES scenarios (A1B, A1FI, A2, and B1). The 13 future climate projection realizations were dynamically downscaled at 9 km resolution by a regional climate model. Using the downscaled variables based on the 13 future climate projection realizations, snow distribution over the Feather, Yuba, and American River watersheds (FRW, YRW, and ARW) was projected by means of the physically-based snow model. FRW and YRW watersheds cover the main source areas of the California State Water Project (SWP), and ARW is one of the key watersheds in the California Central Valley Project (CVP). SWP and CVP are of great importance as they provide and regulate much of the California's water for drinking, irrigation, flood control, environmental, and hydro-power generation purposes. Ensemble average snow distribution over the study watersheds was calculated over the 13 realizations and for each scenario, revealing differences among the scenarios. While the snow reduction through the 21st century was similar between A1B and A2, the snow reduction was milder for B1, and more severe for A1FI. A significant downward trend was detected in the snowpack over nearly the entire watershed areas for all the ensemble average results.

Extracellular matrix metalloproteinase inducer (EMMPRIN) remodels the extracellular matrix through enhancing matrix metalloproteinases (MMPs) and inhibiting tissue inhibitors of MMPs expression in HPV-positive cervical cancer cells.

UNLABELLED: PUPOSE OF INVESTIGATION: To study the expression of extracellular matrix metalloproteinase inducer (EMMPRIN), matrix metalloproteinases (MMPs), and tissue inhibitors of MMP (TIMPs) in uterine cervical cancer cell lines in vitro. MATERIALS AND METHODS: EMMPRIN, MMPs, and TIMPs expression were assessed by Western blot and real-time RT-PCR from cervical carcinoma SiHa, HeLa, and C33-A cells. RESULTS: EMMPRIN recombinant significantly increased MMP-2, MMP-9 protein and mRNA expression in SiHa and Hela cells, but not in C33-A cells by Western blot analysis and real-time RT-PCR. EMMPRIN recombinant significantly inhibited TIMP-1 protein and mRNA levels in SiHa and Hela cells, but not in C33-A cells. There was no difference on the TIMP-2 expression in those cells with the treatment of EMMPRIN recombinant. EMMPRIN RNAi decreased MMP-2 and MMP-9 and increased TIMP-1 expression in SiHa and HeLa cells, but not in C33-A cells. There was no change on the expression of TIMP-2 mRNA levels in SiHa, HeLa and C33-A cells transfected with siEMMPRIN. CONCLUSION: EMMPRIN may induce MMP-2 and MMP-9, and downregulate TIMP-1 in HPV-positive cervical cancer cells in vitro.

Risk of the development of Type 2 diabetes in relation to overall obesity, abdominal obesity and the clustering of metabolic abnormalities in Japanese individuals: does metabolically healthy overweight really exist? The Niigata Wellness Study.

AIMS: We investigated the risk of developing diabetes across various metabolic phenotypes by considering the presence of overall adiposity or abdominal adiposity and the number of metabolic abnormalities and aimed to clarify whether a 'healthy overweight' phenotype, that is, overweight with no metabolic abnormalities, was protective of the development of diabetes. METHODS: We studied 29 564 Japanese individuals without diabetes. The 5-year incidence of diabetes was assessed according to a combination of either overweight (BMI ≥ 25.0 kg/m(2) ) or abdominal obesity (waist circumference ≥ 90 cm in men and ≥ 80 cm in women) and the number of metabolic factors present (hypertension, elevated triglyceride concentration, low HDL cholesterol concentration and impaired fasting glucose). RESULTS: A total of 1188 individuals developed diabetes. Compared with normal weight individuals with none of the four metabolic abnormalities, in overweight individuals with none of the four abnormalities there was an odds ratio (OR) of 2.32 [95% confidence interval (CI) 1.50, 3.59] for diabetes; having any one metabolic abnormality increased the risk of developing diabetes among normal weight individuals [OR 3.23 (2.55, 4.10)] and overweight individuals [OR 5.00 (3.77, 6.63)]. Among overweight individuals, the presence of impaired fasting glucose alone substantially elevated the risk of diabetes by 8.98-fold (5.52, 14.6) in comparison with the absence of the four metabolic factors. CONCLUSIONS: Being 'healthy overweight' was associated with a higher OR of developing future diabetes among Japanese individuals than normal weight individuals with no metabolic abnormalities, and being overweight with one or more abnormalities had a further elevated OR compared with 'healthy overweight' people.

Normal-sized ovary carcinoma syndrome (NOCS) detected with FDG-PET/CT.

BACKGROUND: Normal-sized ovary carcinoma syndrome (NOCS) is an ovarian cancer with ovaries being of normal size, accompanied by diffuse metastatic disease of the peritoneal cavity. CASE: A 39-year-old woman presented with lower abdominal pains. The computed tomopraphy (CT) of the chest, esophagogastroduodenography, and colonoscopy showed no remarkable findings. Amagnetic resonance imaging (MRI) displayed a slightly enlarged right ovary, thickening of the peritoneum, and massive ascites. The right ovary showed high intensity on T2 images and scattered low intensity spots on diffusion-weighted images. The cytology of ascites suspected adenocarcinoma cells. A positron emission tomography (PET) and CT using 18F-fluorodeoxyglucose (FDG) demonstrated markedly increased FDG uptake at the right ovary and peritoneum. The presumptive diagnosis of normal-sized ovary carcinoma syndrome was made. She underwent a total hysterectomy, bilateral salpingo-oophorectomy, pelvic lymphadenectomy, and partial omentectomy. The pathological examination revealed serous cystadenocarcinoma of the right ovary. CONCLUSION: FDG-PET/CT is useful for the detection of NOCS.

Angiomyofibroblastoma of the vulva.

BACKGROUND: Angiomyofibroblastoma (AMF) is a rare benign mesenchymal neoplasm that arises in the pelviperial region. CASE: A patient presented with a painless mass in the right vulva. Under the preoperative diagnosis of Bartholin cyst, she underwent a simple tumor excision. Pathological examination revealed an AMF. Immunohistochemical examination showed that tumor cells were positive for estrogen receptor, progesterone receptor, vimentin, and CD34. She has been with no evidence of local recurrence for ten months after surgery. CONCLUSION: AMF of the vulva is a distinctive mesenchymal tumor that is curable with a simple excision.

Quantitative relationship between body weight gain in adulthood and incident type 2 diabetes: a meta-analysis.

This meta-analysis quantified the risk of type 2 diabetes mellitus (T2DM) preceded by body weight (BW) gain in the general population. Systematic literature searches retrieved 15 eligible studies. The BW gain was divided into early weight-gain, which was defined as BW gain from early adulthood (18-24 years of age) to cohort entry (≥25 years of age), and late weight-gain, which was defined as BW gain from cohort entry. The pooled relative risk (RR; 95% confidence interval [CI]) of T2DM for an increment of BW gain standardized into a 5-kg m(-2) increment in the body mass index (BMI) was 3.07 (2.49-2.79) for early weight-gain and 2.12 (1.74-2.58) for late weight-gain. When limiting analysis to studies that concurrently examined T2DM risk for current BMI (defined in both groups as BMI at cohort entry), a larger magnitude of T2DM risk was revealed for early weight-gain compared with current BMI (RR [95% CI], 3.38 [2.20-5.18] vs. 2.39 [1.58-3.62]), while there was little difference between late weight-gain (RR [95% CI], 2.21 [1.91-2.56]) and current BMI (RR [95% CI], 2.47 [1.97-3.30]). The meta-analysis suggested that BW gain was a quantifiable predictor of T2DM, as well as current obesity in adults. Particularly, BW gain in early rather than middle-to-late adulthood played an important role in developing T2DM.

Transition of low-grade to high-grade endometrial stromal sarcoma: a case report.

BACKGROUND: The transition of low-grade endometrial stromal sarcoma (ESS) to high-grade ESS remains a rare clinical event. CASE: A patient presented with abdominal pain and abnormal genital bleeding. She underwent a supracervical hysterectomy with bilateral salpingo-oophorectomy, omentectomy, and resection of peritoneal disseminated lesions. Pathological examination revealed low-grade ESS in the uterus and omentum. Immunohistochemical examination showed immunoreactivity for CD10 and Ki-67 (MIB1) in the uterus and omentum. However, estrogen receptor, progesterone receptor, alpha-SMA, desmin, h-caldesmon, and CAM5-2 were negative. P53 immunoreactivity was noted only in the omental lesion. Despite performing six courses of adjuvant chemotherapy, she recurred in the abdomen. She underwent ileostomy and resection of peritoneal disseminated lesions. Pathology showed high-grade ESS in the recurrent lesion of the ileum, which was characterized by severe cytologic atypia, high mitotic index, multifocal necrosis, increased Ki-67 index, and immunoreactivity for p53. CONCLUSION: Although rare, the transition of low-grade ESS to high-grade ESS may occur and suggests the worsening of the prognosis. Pathological examination and immunohistochemistry are useful for the diagnosis of the transition of low-grade ESS to high-grade ESS.

Superior sagittal sinus dural arteriovenous fistulas treated by stent placement for an occluded sinus and transarterial embolization. A case report.

We describe a case of dural arteriovenous fistulas (DAVFs) involving the superior sagittal sinus (SSS) successfully treated with stent placement for an occluded sinus and transarterial embolization. A 61-year-old man who had been treated with anticoagulation for a known SSS thrombosis presented with a sudden onset of headache. CT scan revealed an intraventricular hemorrhage and cerebral angiography revealed DAVFs involving the SSS which had severe venous congestion and sinus occlusion. We treated this case with a staged endovascular approach which consisted of stent placement for the occluded sinus and transarterial intravenous embolization resulting in complete eradication of DAVFs. Recanalization of an occluded sinus by stent placement can reduce venous congestion and transarterial intravenous embolization can obliterate dural arteriovenous shunts. This staged strategy is feasible and should be considered a first option of treatment, especially for DAVFs which presented with intracranial hemorrhage and aggressive venous hypertension.

Synergistic action of Smad4 and Pten in suppressing pancreatic ductal adenocarcinoma formation in mice.

Mutations of SMAD4/DPC4 are found in about 60% of human invasive pancreatic ductal adenocarcinomas (PDACs); yet, the manner in which SMAD4 deficiency enhances tumorigenesis remains elusive. Using a Cre-LoxP approach, we generated a mutant mouse carrying a targeted deletion of Smad4 in the pancreas. We showed that the absence of Smad4 alone did not trigger pancreas tumor formation; however, it increased the expression of an inactivated form of Pten, suggesting a role of Pten in preventing Smad4-/- cells from undergoing malignancy. To investigate this, we disrupted both Pten and Smad4. We showed that Pten deficiency initiated widespread premalignant lesions, and a low tumor incidence that was significantly accelerated by Smad4-deficiency. The absence of Smad4 in a Pten-mutant background enhanced cell proliferation and triggered transdifferentiation from acinar, centroacinar and islet cells, accompanied by activation of Notch1 signaling. We showed that all tumors developed in the Smad4/Pten-mutant pancreas exhibited high levels of pAKT and mTOR, and that about 50 and 83% of human pancreatic cancers examined showed increased pAKT and pmTOR, respectively. Besides the similarity in gene expression, the pAKT and/or pmTOR-positive human PDACs and mouse pancreatic tumors also shared some histopathological similarities. These observations indicate that Smad4/Pten-mutant mice mimic the tumor progression of human pancreatic cancers that are driven by activation of the AKT-mTOR pathway, and uncovered a synergistic action of Smad4 and Pten in repressing pancreatic tumorigenesis.

Porphyromonas gingivalis mutant defective in a putative extracytoplasmic function sigma factor shows a mutator phenotype.

INTRODUCTION: Porphyromonas gingivalis is implicated as a major pathogen in the development and progression of chronic periodontitis. P. gingivalis must possess the ability to tolerate stress signals outside the cytoplasmic membrane by transcriptional activation of genes encoding proteins involved in defense or repair processes. Some bacteria utilize a distinct subfamily of sigma factors to regulate extracytoplasmic function (hence termed the ECF subfamily). METHODS: To elucidate their role in P. gingivalis, a chromosomal mutant carrying a disruption of an ECF sigma factor PG1318-encoding gene was constructed. Hemagglutination and proteolytic activities were measured in the PG1318-defective mutant. Reverse transcription-polymerase chain reaction (RT-PCR) analysis and southern blot analysis were used to assess transcription of kgp in the PG1318-defective mutant. Frequency of spontaneous mutation that conferred resistance to l-trifluoromethionine was measured in the PG1318-defective mutant. RESULTS: The PG1318-defective mutant formed non-pigmented colonies on blood agar plates at a relatively high frequency. Arginine-specific and lysine-specific proteinase activities of the non-pigmented variants were remarkably decreased compared with those of the parent strain and the pigmented variants. RT-PCR analysis showed that kgp was not transcribed in some non-pigmented variants and southern blot analysis revealed that there was a deletion in their kgp region. Frequency of mutation conferring resistance to l-trifluoromethionine was significantly higher in the PG1318-defective mutant than in the wild-type. CONCLUSION: These results suggest that PG1318 plays a role in the regulation of mutation frequency in the bacterium.

A putative role of versican in uterine leiomyomas.

The extracellular matrix (ECM) has been thought to contribute to the pathogenesis of uterine leiomyomas. Uterine leiomyomas have abundant ECM components, including collagen, fibronectin, and glycosaminoglycans. Recent studies have demonstrated the overexpression of versican in uterine leiomyomas. Versican is a chondroitin sulfate proteoglycan that constitutes the main component of the ECM. However, the role of versican in the growth of uterine leiomyomas remains unknown. In this article a putative role of versican in uterine leiomyomas is discussed in association with cell proliferation and apoptosis..

Ruptured cornual pregnancy: case report.

Cornual pregnancy is uncommon among ectopic pregnancies. A diagnosis of cornual pregnancy remains challenging, and rupture of a cornual pregnancy causes catastrophic consequence due to massive bleeding. We report a case of a ruptured cornual pregnancy occurring at 12 weeks of gestation. A 34-year-old woman was suspected of having a left cornual pregnancy at 11 weeks of gestation. Transabdominal ultrasound and magnetic resonance imaging revealed an eccentric localization of a gestational sac containing a viable fetus outside the uterine cavity adjacent to the left uterine cornua. The gestational sac was surrounded with a thin myometrial layer. The patient developed a rupture of the left cornual pregnancy with unstable hemodynamics. She underwent emergency laparotomy, which revealed the ruptured left cornual pregnancy with a hemoperitoneum. Cornual resection was performed. The pathological examination confirmed a ruptured cornual pregnancy.

Regulation of matrix contraction in chronic venous disease.

OBJECTIVE: The role of TGF-beta(1) in venous ulcer healing and the signalling cascades regulating dermal fibroblast function are poorly understood. To elucidate these processes, we hypothesized that TGF-beta(1) facilitates wound healing by increasing chronic venous insufficiency (CVI) induced matrix contraction via intracellular cross-talk between TGF-beta(1) and the ERK-1/2 MAP kinase signalling cascades. METHODS: Fibroblasts isolated from calf biopsies (LC) of patients with different severity of CVI (CEAP, Clinical Etiological Anatomical Pathological classes) were seeded into 200 microl collagen gels under isometric conditions. Fibroblasts from neonatal foreskins (HS68), non-CVI patients (NC), and the ipsilateral normal thigh of each CVI patient (LT) served as controls. Thirteen patients with CVI (class 2, n=5; class 4, n=5; class 6, n=3) and 2 non-CVI controls (NC, n=2) were included in the study. All experimental conditions were determined by dose-response and time-course experiments. Gels were cultured with/without 0.1 ng/ml TGF-beta(1) and with/without 50 microM PD98059 (MEK and downstream-MAPK inhibitor). Additional patient fibroblasts were transfected with constitutively active Ras (pCMV-Ras) or an empty vector (pCMV-beta) with/without 0.1 ng/ml TGF-beta(1) and with/without 50 microm PD98059. The collagen gels were released after 4 days and the percent contraction was determined by area measurements using image analysis. Differences in alpha-smooth muscle actin (alpha-SMA) and ERK-1/2 MAPK (phosphorylated and total) protein levels were analyzed with western blotting. RESULTS: Gels seeded with CVI fibroblasts contracted more than HS68, NC and LT fibroblasts. Inhibition of MAPK and/or stimulation with TGF-beta(1) increased the contraction of LC gels compared to unstimulated controls. Agonist induced gel contraction correlated with CVI disease severity. alpha-SMA protein expression in LC fibroblasts increased with MAPK inhibition with/without TGF-beta(1) stimulation, and correlated with the degree of gel contraction. Transfection with pCMV-Ras (activator of ERK-1/2) inhibited gel contraction; this inhibition was not reversed by addition of TGF-beta(1). Transfection with the pCMV-beta empty vector had no effect on gel contraction. CONCLUSIONS: TGF-beta1 stimulation of CVI patient fibroblasts grown in 3D collagen gels results in conversion to a contractile phenotype through upregulation of alpha-SMA, and in enhanced gel contraction. Inhibition of MAPK further increases gel contraction, while Ras activation of ERK-1/2 inhibits TGF-beta1-induced gel contraction. These responses correlate with increasing CEAP severity. CVI fibroblast mediated gel contraction is therefore regulated through cross-talk between the ERK-1/2 MAPK and TGF-beta(1) signalling cascades. These data identify potentially clinically relevant therapeutic molecular targets that could enhance matrix contraction and thereby improve venous ulcer wound healing.

Sex steroidal modulation of collagen metabolism in uterine leiomyomas.

Uterine leiomyoma is a fibrotic disease that contains abundant extracellular matrix (ECM) components, particularly collagen fibrils. Aberrant ECM metabolism has been thought to contribute to the pathogenesis of uterine leiomyomas. However, it remains poorly understood whether ovarian sex steroid hormones modulate collagen metabolism in uterine leiomyomas. More recently, a few articles have demonstrated the differential effects of ovarian sex steroids, selective estrogen receptor modulators (SERMs), and selective progesterone receptor modulators (SPRMs) on the induction of the ECM-remodeling enzymes and collagen synthesis in uterine leiomyoma cells. Sex steroids may act to up-regulate collagen synthesis, whereas SERMs and SPRMs down-regulate collagen synthesis. Further study will be needed to clarify the precise mechanism underlying steroidal regulation of collagen synthesis in uterine leiomyomas.

The development of placenta increta following pelvic transcatheter artery embolization for postpartum hemorrhage.

OBJECTIVE: Pelvic transcatheter artery embolization (TAE) has been widely used for the management of postpartum hemorrhage (PPH). However, the adverse effects of TAE on the subsequent pregnancy remain poorly understood. CASE: A 30-year-old woman, gravida 2, para 1, developed PPH due to atonic bleeding and underwent TAE. Thereafter, her menstrual cycle became irregular with less blood volume. Three years later, she became pregnant despite a thin endometrial thickness of 6 mm during the ovulatory period. She delivered a healthy baby at 39 weeks of gestation. No signs of placental separation were obtained, and an attempt at manual extraction of the placenta failed, followed by massive PPH. She underwent emergent TAE. The placenta was not spontaneously delivered even on day 8 postpartum. A supracervical hysterectomy was performed due to a worsening intrauterine infection. Pathological examination revealed findings compatible with placenta increta. CONCLUSION: A TAE-associated thin endometrium may be attributable to the development of placenta increta. Pregnant women undergoing TAE should be managed carefully because the information about pregnancy outcomes after TAE remains scanty.

Proteome analysis of Porphyromonas gingivalis cells placed in a subcutaneous chamber of mice.

INTRODUCTION: Porphyromonas gingivalis, an oral anaerobic bacterium, is considered a major pathogen for chronic periodontitis. Pathogenic bacteria usually upregulate or downregulate gene expression to combat the protective responses of their hosts. METHODS: To determine what protein is regulated when P. gingivalis cells invade host tissues, we analyzed the proteome of P. gingivalis cells that were placed in a mouse subcutaneous chamber by two-dimensional gel electrophoresis and mass spectrometry. RESULTS: Fourteen proteins were upregulated, while four proteins were downregulated. We focused on three upregulated proteins, PG1089 (DNA-binding response regulator RprY), PG1385 (TPR domain protein), and PG2102 (immunoreactive 61-kDa antigen), and constructed mutant strains that were defective in these proteins. Mouse abscess model experiments revealed that the mutant strain defective in PG1385 was clearly less virulent than the wild-type parent strain. CONCLUSION: These results indicate that the PG1385 protein is involved in P. gingivalis virulence and that the method used here is useful when investigating the P. gingivalis proteins responsible for virulence.

Association study of vascular endothelial growth factor gene polymorphisms in endometrial carcinomas in a Japanese population.

OBJECTIVE: Vascular endothelial growth factor (VEGF) is one of the most potent endothelial cell mitogens and plays a critical role in angiogenesis of endometrial carcinomas. Several studies have demonstrated positive associations between VEGF gene polymorphisms and several carcinomas. In this study we investigated whether VEGF gene polymorphisms are associated with endometrial carcinomas in a Japanese population. METHODS: The allele frequencies and genotype distributions of VEGF -460 C/T, +405 G/C, and +936 C/T polymorphisms were examined in 105 endometrial carcinomas and 179 controls using PCR-RFLP analysis. An association of these polymorphisms with three-year disease-free survival was evaluated using the Kaplan-Meier method. RESULTS: No significant differences in the allele frequencies and genotype distributions of VEGF -460 C/T (p = 0.54, 0.90), +405 G/C (p = 0.31, 0.17), and +936 C/T polymorphisms (p = 0.46, 0.24) were observed between endometrial carcinoma patients and controls. There were no significant differences in the frequencies of haplotype -460 T/+405 C between patients and controls. Futhermore, VEGF -460 C/T, +405 G/C, and +936 C/T polymorphisms were not associated with three-year disease-free survival of endometrial carcinoma patients. CONCLUSIONS: Although limited by sample size, our study did not demonstrated any evidence that VEGF -460 C/T, +405 G/C, and +936 C/T polymorphisms are associated with an increased risk of endometrial carcinomas in Japanese women.

Action of progesterone receptor modulators on uterine leiomyomas.

Novel progesterone receptor modulators (PRMs) have recently been demonstrated to be effective in the treatment of patients with symptomatic uterine leiomyomata. PRMs are shown to reduce leiomyoma size and improve leiomyoma-associated symptoms. However, the precise mechanisms underlying the action of PRMs remain to be elucidated. My co-workers and I have investigated in vitro action of PRMs in cultured leiomyoma cells and revealed that PRMs inhibit cell proliferation and induce apoptosis of leiomyoma cells. Moreover, our recent studies show that PRMs can modulate the metabolism of extracellular matrix proteins in cultured leiomyoma cells toward the collagenolysis. The update about an action of PRMs in uterine leiomyoma cells in vitro is described in this article.