Adenomyotic glands are highly related to endometrial glands.

RESEARCH QUESTION: How closely related are adenomyotic and endometrial glands? DESIGN: In this study, the mRNA and protein database www.proteinatlas.org was searched for proteins expressed predominantly in the endometrial glands. Specificity was tested with tissue microarrays. Biopsy specimens of endometrial, adenomyotic tissue, or both, were collected after surgery from 21 women without endometriosis, 20 women with endometriosis, 18 women with adenomyosis together with endometriosis and 12 women with adenomyosis alone. Tissue expression was analysed by immunohistochemistry. RESULTS: Two proteins were identified: calcyphosine (CAPS), and msh homeobox 1 (MSX1). A high abundance and good specificity in endometrial glands were found. Both proteins, CAPS and MSX1, showed a high specificity for endometrium and are both localized in the luminal cells and epithelial cells of the glandular and adenomyotic glands. No significant differences were found between CAPS- and MSX1-positive endometrial glands between cases with and without endometriosis. Also, no cycle-specific different expression was found. Furthermore, a close relationship between the adenomyotic glands and the endometrial glands for CAPS (range 63.0-98.3%) and for MSX1 (range 87.1-99.3%) could be demonstrated. Only 11.2% and 6.8% negative glands for CAPS and MSX1 were identified in all tissues from all patients, respectively; none were negative for both proteins. CONCLUSIONS: Taken together, our results show that the protein expression pattern of adenomyosis is nearly identical to those of the endometrium with and without endometriosis, thus suggesting endometrial glands as the main source for adenomyotic glands.

Inhibitory effects of mushroom extracts on progression of carcinogenesis in mice.

OBJECTIVE: Hepatocellular carcinoma is a common primary malignancy of hepatocytes that has caused many fatalities globally. To manage the increasing cases of hepatocellular carcinoma, natural products like mushrooms have been tested for their anti-oxidant, anti-tumour and therapeutic properties. This study aimed to investigate the effect of Agaricus bisporus on progression of chemically induced carcinogenesis in mice. Carcinogenesis was induced in experimental and positive group of mice. Development and progression of carcinogenesis was monitored by quantifying levels of Lactate dehydrogenase, total sialic acid and by histological analysis. The results of the study showed that, unlike lactate dehydrogenase, the levels of sialic acid consistently decreased throughout the experimental period in mice that were fed on mushroom extracts compared to the positive control. Histological analysis also showed protection of the hepatocytes from carcinogenesis progression. Overall, the results from tumour markers and histological analysis, showed that addition of Agaricus bisporus extracts to diet slowed down progression of carcinogenesis and these extracts therefore may be useful as supplementary diet to conventional cancer therapies.

Parasite accumulation in placenta of non-immune baboons during Plasmodium knowlesi infection.

BACKGROUND: Placental malaria (PM) causes adverse pregnancy outcomes in the mother and her foetus. It is difficult to study PM directly in humans due to ethical challenges. This study set out to bridge this gap by determining the outcome of PM in non-immune baboons in order to develop a non-human primate model for the disease. METHODS: Ten pregnant baboons were acquired late in their third trimester (day 150) and randomly grouped as seven infected and three non-infected. Another group of four nulligravidae (non-pregnant) infected was also included in the analysis of clinical outcome. Malaria infection was intravenously initiated by Plasmodium knowlesi blood-stage parasites through the femoral vein on 160(th) day of gestation (for pregnant baboons). Peripheral smear, placental smear, haematological samples, and histological samples were collected during the study period. Median values of clinical and haematological changes were analysed using Kruskal-Wallis and Dunn's Multiple Comparison Test. Parasitaemia profiles were analysed using Mann Whitney U test. A Spearman's rank correlation was run to determine the relationship between the different variables of severity scores. Probability values of P <0.05 were considered significant. RESULTS: Levels of white blood cells increased significantly in pregnant infected (34%) than in nulligravidae infected baboons (8%). Placental parasitaemia levels was on average 19-fold higher than peripheral parasitaemia in the same animal. Infiltration of parasitized erythrocytes and inflammatory cells were also observed in baboon placenta. Malaria parasite score increased with increase in total placental damage score (rs = 0.7650, P <0.05) and inflammatory score (rs = 0.8590, P <0.05). Although the sample size was small, absence of parasitized erythrocytes in cord blood and foetal placental region suggested lack of congenital malaria in non-immune baboons. CONCLUSION: This study has demonstrated accumulation of parasitized red blood cells and infiltration of inflammatory cells in the placental intravillous space (IVS) of baboons that are non-immune to malaria. This is a key feature of placental falciparum malaria in humans. This presents the baboon as a new model for the characterization of malaria during pregnancy.

The Different Gene Expression Profile in the Eutopic and Ectopic Endometrium Sheds New Light on the Endometrial Seed in Endometriosis.

The changes in endometrial cells, both in the eutopic endometrium of patients with and without endometriosis and in lesions at ectopic sites, are frequently described and often compared to tumorigenesis. In tumorigenesis, the concept of "seed and soil" is well established. The seed refers to tumor cells with metastatic potential, and the soil is any organ or tissue that provides a suitable environment for the seed to grow. In this systematic review (PRISMA-S), we specifically compared the development of endometriosis with the "seed and soil" hypothesis. To determine changes in the endometrial seed, we re-analyzed the mRNA expression data of the eutopic and ectopic endometrium, paying special attention to the epithelial-mesenchymal transition (EMT). We found that the similarity between eutopic endometrium without and with endometriosis is extremely high (~99.1%). In contrast, the eutopic endometrium of patients with endometriosis has a similarity of only 95.3% with the ectopic endometrium. An analysis of EMT-associated genes revealed only minor differences in the mRNA expression levels of claudin family members without the loss of other cell-cell junctions that are critical for the epithelial phenotype. The array data suggest that the changes in the eutopic endometrium (=seed) are quite subtle at the beginning of the disease and that most of the differences occur after implantation into ectopic locations (=soil).

Analysis of Membrane Type-1 Matrix Metalloproteinase (MT1-MMP, MMP14) in Eutopic and Ectopic Endometrium and in Serum and Endocervical Mucus of Endometriosis.

BACKGROUND: Membrane type-matrix metalloproteinases (MT-MMPs) are a subgroup of the matrix metalloproteinases (MMPs) family and are key molecules in the degradation of the extracellular matrix. Membrane type-1 matrix metalloproteinase (MT1-MMP, MMP14) is often deregulated in different cancer tissues and body fluids of human cancer patients; however, MT1-MMP levels in endometriosis and adenomyosis patients are currently unknown. MATERIALS AND METHODS: Tissue samples from patients with and without endometriosis or adenomyosis were analyzed with immunohistochemistry for the localization of MT1-MMP. Serum and endocervical mucus samples from patients with and without endometriosis or adenomyosis were investigated with MT1-MMP ELISAs. RESULTS: MT1-MMP was localized preferentially in the glands of eutopic and ectopic endometrium. MT1-MMP protein levels are significantly reduced in ovarian endometriosis (HSCORE = 31) versus eutopic endometrium (HSCORE = 91) and adenomyosis (HSCORE = 149), but significantly increased in adenomyosis (HSCORE = 149) compared to eutopic endometrium (HSCORE = 91). Similarly, analysis of the levels of MT1-MMP using enzyme-linked immune assays (ELISAs) demonstrated a significant increase in the concentrations of MT1-MMP in the serum of endometriosis patients (1.3 ± 0.8) versus controls (0.7 ± 0.2), but not in the endocervical mucus. Furthermore, MT1-MMP levels in the endocervical mucus of patients with endometriosis were notably reduced in patients using contraception (3.2 ± 0.4) versus those without contraception (3.8 ± 0.2). CONCLUSIONS: Taken together, our findings showed an opposite regulation of MT1-MMP in the tissue of ovarian endometriosis and adenomyosis compared to eutopic endometrium without endometriosis but increased serum levels in patients with endometriosis.

Role of Betaglycan in TGF-ß Signaling and Wound Healing in Human Endometriotic Epithelial Cells and in Endometriosis.

Endometriosis is characterized by the presence of ectopic endometrium most often in the pelvis. The transforming growth factor-beta (TGF-ß) superfamily is also involved in the pathogenesis; however, betaglycan (BG, syn. TGF-ß type III receptor) as an important co-receptor was not studied. We analyzed mainly BG ectodomain shedding because released soluble BG (sBG) often antagonizes TGF-ß signaling. Furthermore, we studied the role of TGF-ßs and BG in wound healing and evaluated the suitability of BG measurements in serum and endocervical mucus for non-invasive diagnosis of endometriosis. Evaluation of the BG shedding and signaling pathways involved as well as wound healing was performed with enzyme-linked immune assays (ELISAs), reverse transcription-quantitative polymerase chain reaction (RT-qPCR), small interfering RNA (siRNA) knockdown, and scratch assays with human endometriotic epithelial cells. TGF-ß1/2 stimulation resulted in a significant dose-dependent reduction in BG shedding in endometriotic cells, which was TGF-ß/activin receptor-like kinase-5 (ALK-5)/mother against decapentaplegic homolog3 (SMAD3)- but not SMAD2-dependent. Inhibition of matrix metalloproteinases (MMPs) using the pan-MMP inhibitor GM6001 and tissue inhibitor of MMPs (TIMP3) equally attenuated BG shedding, signifying the involvement of MMPs in shedding. Likewise, recombinant BG moderately reduced the secretion of TGF-ß1/2 and wound healing of endometriotic cells. TGF-ß1 significantly enhanced the secretion of MMP2 and MMP3 and moderately promoted wound healing. In order to evaluate the role of BG in endometriosis, serum (n = 238) and mucus samples (n = 182) were analyzed. Intriguingly, a significant reduction in the levels of sBG in endocervical mucus but not in the serum of endometriosis patients compared to controls was observed. Collectively, these observations support a novel role for BG in the pathophysiology of endometriosis.

Impaired Expression of Membrane Type-2 and Type-3 Matrix Metalloproteinases in Endometriosis but Not in Adenomyosis.

Matrix metalloproteinases (MMPs) play an important role in menstruation and endometriosis; however, the membrane-type matrix metalloproteinases (MT-MMPs) are not well studied in endometriosis and adenomyosis. We analyzed MT2-MMP (MMP15) and MT3-MMP (MMP16) in eutopic endometrium with and without endometriosis and with and without adenomyosis and ectopic endometrium of deep infiltrating endometriosis (DIE), peritoneal endometriosis (PE), and ovarian endometriosis (Ov) by immunohistochemistry. Preferential expression of both proteins was observed in the glandular and luminal epithelial cells of the eutopic endometrium of patients with and without endometriosis with a ~2.5-fold stronger expression of MT3-MMP compared to MT2-MMP. We did not observe any differences during menstrual cycling and in eutopic endometrium of patients with and without endometriosis. Similarly, eutopic endometrium and adenomyotic tissue with and without endometriosis showed similar protein levels of MT2-MMP and MT3-MMP. In contrast, MT2-MMP and MT3-MMP protein was decreased in ectopic compared to eutopic endometrium and adenomyosis. The similar expression of MT2-MMP and MT3-MMP in eutopic endometrium in patients with and without endometriosis in contrast to the impaired expression in ectopic endometrium suggests that alterations occur after and not before endometrial implantation possibly by distinct interactions with the different environments. The differential protein expression of MT2/3-MMP in adenomyosis compared to endometriosis might suggest a different pathogenesis pathway for the two diseases.

Activin A Modulates Betaglycan Shedding via the ALK4-SMAD3-Dependent Pathway in Endometriotic Cells.

The TGF-ß superfamily members, activins and inhibins, are mainly involved in cell proliferation, cell survival, invasion, immune surveillance, and lesion growth in endometriosis. Herein, we investigated the modulation of the TGF-ß type III receptor (betaglycan or BG) by activin A and inhibin A in endometriosis in vitro. Often, BG undergoes ectodomain shedding releasing soluble BG (sBG) which frequently antagonizes TGF-ß signaling. The effects of activin A on BG shedding and signaling pathways involved were evaluated with the inhibitors LY364947 and SIS3, siRNA knockdown in human endometrial cells (12Z, THESC, Ishikawa, and primary stromal cells) and were quantified with BG ELISAs. The effects of activin A and inhibin A on the secretion of MMP2 and MMP3 were analyzed using ELISAs. The effects of activin A on the BG expression were analyzed using RT-qPCR and western blot. The CCK-8 and BrdU assays were used to evaluate the effects of the recombinant BG on cell viability and proliferation. Activin A stimulation resulted in a significant time- and dose-dependent reduction in BG shedding, which was found to be activin A/ALK-4/SMAD3- but not SMAD2-dependent. Activin A increased the BG mRNA expression but had no effect on the protein expression. Likewise, inhibin A was found to block BG shedding. Activin A, but not inhibin A, significantly enhanced the secretion of MMP2 and MMP3. The recombinant BG had no effect on the viability and proliferation of endometriotic cells. Together, these observations support a novel role for activin A with BG in modulating the TGF-ß superfamily ligands in endometrial cells in vitro.

The Importance of Stromal Endometriosis in Thoracic Endometriosis.

Thoracic endometriosis (TE) is a rare type of endometriosis, where endometrial tissue is found in or around the lungs and is frequent among extra-pelvic endometriosis patients. Catamenial pneumothorax (CP) is the most common form of TE and is characterized by recurrent lung collapses around menstruation. In addition to histology, immunohistochemical evaluation of endometrial implants is used more frequently. In this review, we compared immunohistochemical (CPE) with histological (CPH) characterizations of TE/CP and reevaluated arguments in favor of the implantation theory of Sampson. A summary since the first immunohistochemical description in 1998 until 2019 is provided. The emphasis was on classification of endometrial implants into glands, stroma, and both together. The most remarkable finding is the very high percentage of stromal endometriosis of 52.7% (CPE) compared to 10.2% (CPH). Chest pain, dyspnea, right-sided preference, and diaphragmatic endometrial implants showed the highest percentages in both groups. No significant association was found between the recurrence rate and the various appearances of endometriosis. Sometimes in CPE (6.8%) and CPH (30.6%) no endometrial implants were identified underlining the importance of sensitive detection of endometriosis during and after surgery. We suggest that immunohistochemical evaluation should become mandatory and will improve diagnosis and classification of the disease.

Role of TGF-betas in normal human endometrium and endometriosis.

Endometriosis is characterized by presence of endometrial tissue outside the uterus. Prevalence is estimated at 6-10% in the general female population and many patients experience pain and/or infertility. Diagnosis is achieved by laparoscopic intervention followed by histological confirmation of viable endometriotic tissue. Mild cases are managed medically with contraceptive steroids and non-steroidal anti-inflammatory agents. Surgery provides relief to women in pain but symptoms recur in 75% of cases within 2 years. Starting with menstruation, we have categorized endometriosis into six stages, namely (1) shedding of cells, (2) cell survival, (3) escape from immune surveillance, (4) adhesion to peritoneum, (5) angiogenesis and (6) bleeding. In most of these biological processes, which resemble metastasis, transforming growth factor-beta (TGF-betas) and their high-affinity receptors are involved directly or indirectly. TGF-betas are abundantly and differentially expressed in the endometrium under hormonal control. Although they are preferentially synthesized in the stroma, glands and macrophages also secrete TGF-betas into the uterine fluid, where interaction with preimplantation embryos is suspected. Because mRNA and protein expression of all three TGF-betas is increased around menstruation, we suggest that TGF-betas might be involved in initiation of menstruation. Furthermore, because of high postmenstrual TGF-beta3 levels, we suppose that it might participate in scarless postmenstrual regeneration of endometrium. Our suggestions pave the way to novel routes of investigation into the roles of TGF-betas during menstruation and endometriosis.

Impact of endometriosis on quality of life: a pilot study.

Endometriosis affects 6-10% of women in reproductive age, 35-50% of whom experience pain, infertility or both. Mild cases are managed medically but surgery provides relief to women in pain. However, symptoms recur in 75% of cases within 2 years. We investigated the impact of endometriosis on quality of life among 65 women aged 18-60 years working at a city supermarket in Giessen, Germany. Of the 65 women, 12 had undergone surgeries, 22 had dysmenorrhoea, 24 dyspareunia and 3 were infertile. Of the 22 women with dysmenorrhoea, 10 had difficulties performing gardening, housework, sports and leisure activities. Five of these 10 women experienced social isolation, 6 professional setbacks; 6 declined efficiency at work and 3 had taken time off work. Of the 24 women with dyspareunia, 7 experienced minimal, 12 light and 5 moderate to strong pain. Only 16 of these 24 women discussed the problem with their partners. This study demonstrates that pain is a major cause of physical, psycho-social, emotional and professional or work related impairment among women with endometriosis. Because endometriosis is likely to impose emotional and financial burdens, we suggest that future studies should be extended to include interviews with family members.

Similar Characteristics of Endometrial and Endometriotic Epithelial Cells.

Epithelial-mesenchymal transition (EMT) is characterized by the loss of epithelial and acquisition of mesenchymal cell characteristics. Our aim was to assess the epithelial phenotype in the pathogenesis of endometriosis with epithelial and mesenchymal markers. We used 2 structural (keratin-18, -19 [K18, K19]), 1 membrane-associated (mucin-1 [MUC1]), and 2 mesenchymal proteins (vimentin; zinc finger E-box-binding homeobox 1, [ZEB1]) to compare epithelial and mesenchymal characteristics in eutopic endometrium with the 3 endometriotic entities, peritoneal, ovarian, and deep infiltrating endometriosis (DIE). Quantitation showed no differences for K18, K19, and MUC1 between endometrium with and without endometriosis. Also, K18 was not different between endometrium and endometriotic lesions. In contrast, K19 and MUC1 were modestly but significantly decreased in the endometriotic lesions compared to endometrium. However, the maintained expression of epithelial markers in all investigated tissues, regardless of the pathological condition, clearly indicates no loss of the epithelial phenotype. This is further supported by the reduced presence of epithelial vimentin in endometriotic lesions which is in contrast to an increase in stromal vimentin in ectopic endometrium, especially in ovarian endometriosis. The ZEB1 increase in endometriotic lesions, especially in DIE, on the other hand suggests a role of partial EMT in the development of endometriotic lesions, possibly connected with the gain of invasive capabilities or stemness. Taken together, although we found some hints for at least a partial EMT, we did not observe a severe loss of the epithelial cell phenotype. Thus, we propose that EMT is not a main factor in the pathogenesis of endometriosis.

Mushroom polysaccharide extracts delay progression of carcinogenesis in mice.

Hepatocellular carcinoma results when cancerous cells are localized in the liver. It is distributed globally with high prevalence in sub-Saharan African, southern Asia, China and Japan. Diagnosis is experimental and in many cases inaccurate due to unreliability of markers. Prognosis is poor and the cost of treatment prohibitive. Conventional radiation and chemotherapy lead to loss of hair, fertility and general weakening of the body's immune system increasing a patient's risk to infection. These observations underscore the need for improved, or additional methods of cancer diagnosis and management. We investigated the effect of polysaccharide rich Pleurotus pulmonarius fruit body extracts on progression of chemically induced hepatocellular carcinoma in CBA mice. Addition of Pleurotus pulmonarius extracts in diet delayed progression of carcinogenesis suggesting that these extracts may be useful as adjuvants to conventional cancer therapies.

Safety, immunogenicity, and cross-species protection of a plasmid DNA encoding Plasmodium falciparum SERA5 polypeptide, microbial epitopes and chemokine genes in mice and olive baboons.

Incorporation of biomolecular epitopes to malarial antigens should be explored in the development of strain-transcending malarial vaccines. The present study sought to determine safety, immunogenicity and cross-species efficacy ofPlasmodium falciparum serine repeat antigen 5 polypeptide co-expressed with epitopes of Bacille-Calmette Guerin (BCG), tetanus toxoid (TT) and a chemokine gene. Olive baboons and BALB/c mice were randomly assigned into vaccine and control groups. The vaccine group animals were primed and boosted twice with pIRES plasmids encoding the SERA5+ BCG+ TT alone, or with either CCL5 or CCL20 and the control group with pIRES plasmid vector backbone. Mice and baboons were challenged withP. berghei ANKA and P. knowlesi H strain parasites, respectively. Safety was determined by observing for injection sites reactogenicities, hematology and clinical chemistry. Parasitaemia and survivorship profiles were used to determine cross-species efficacy, and T cell phenotypes, Th1-, Th2-type, T-regulatory immune responses and antibody responses were assessed to determine vaccine immunogenicity. The pSeBCGTT plasmid DNA vaccines were safe and induced Th1-, Th2-type, and T-regulatory responses vaccinated animals showed enhanced CD4+ (P<0.01), CD 8+ T cells (P<0.001) activation and IgG anti-SE36 antibodies responses (P<0.001) at week 4 and 8 post vaccination compared to the control group. Vaccinated mice had a 31.45-68.69% cumulative parasite load reduction and 60% suppression in baboons (P<0.05) and enhanced survivorship (P<0.001) with no clinical signs of malaria compared to the control group. The results showed that the vaccines were safe, immunogenic and conferred partial cross-species protection.

PAI-1 secretion of endometrial and endometriotic cells is Smad2/3- and ERK1/2-dependent and influences cell adhesion.

In the endometrium transforming growth factor-betas (TGF-ßs) are involved mainly in menstruation and endometriosis. After binding of the ligands to the high-affinity receptors, TGF-ß receptors (TBR1 and TBR2), TGF-ßs activate Smad signaling to modulate gene expression and cellular functions. However, recently also Smad-independent pathways have been studied in more details. To evaluate both pathways, we have analyzed TGF-ß signaling in human endometrial and endometriotic cells. Although endometrial and endometriotic cells secrete TGF-ß1, secretion by stromal cells was higher compared to epithelial cells. In contrast, secretion of TGF-ß2 was higher in endometriotic stromal and endometriotic epithelial cells compared to normal endometrial cells. Treatment of endometrial and endometriotic stromal and epithelial cells with TGF-ß1 or TGF-ß2 increased Smad-dependent secretion of plasminogen activator inhibitor-1 (PAI-1) dramatically in all three cell lines. Of note, endometriotic cells secreted clearly higher levels of PAI-1 compared to endometrial cells. Whereas a TBR1 kinase inhibitor completely blocked the TGF-ß1 or TGF-ß2-induced PAI-1 secretion, an ERK1/2 inhibitor only partially reduced PAI-1 secretion. This inhibition was not dependent on epidermal growth factor receptor (EGFR) activation by phosphorylation but on kinase activity of the TBR1. Finally, treatment of endometrial and endometriotic cell lines with recombinant PAI-1 showed reduced cell adhesion, especially of the endometrial cells. In summary, our results demonstrate that both Smad-dependent and TBR1-dependent ERK1/2 pathways are necessary for TGF-ß-dependent high level secretion of PAI-1, which might increase cellular deadhesion.

Pregnancy-preserving myomectomy: preliminary report on a new surgical technique.

Uterine myomas are found in 0.3-2.6% of pregnant women. In one case out of ten they cause complications. Treatment is primarily conservative but in cases of failure, surgery cannot be avoided. We present a case of a pregnant woman with myomas. Because of failure of conservative management and severe abdominal pain, we performed a myomectomy at 18 weeks' gestation with preservation of the pregnancy. We describe a modified surgical technique whereby interrupted sutures are first placed around the myoma for haemostasis. We achieved good pregnancy outcome by caesarean section carried out near term. Incidence, presentation, and challenges associated with the management of myomas during pregnancy are briefly discussed.

Polymorphisms in the Paan-AG promoter influence NF-kappaB binding and transcriptional activity.

The human leukocyte antigen-G (HLA-G) gene encodes a protein that is highly expressed at the human maternal-fetal interface during pregnancy and may be critical to the survival of the semiallogenic fetus. A unique feature of this gene is a 13-bp deletion in the proximal promoter that renders it unresponsive to transactivation by the nuclear factor-kappaB (NF-kappaB). We previously showed that the proximal promoter of Paan-AG, the functional homologue of HLA-G in the olive baboon (Papio anubis), is intact. We cloned the promoters of two putative Paan-AG alleles (AG1 and AG2) and identified a number of regulatory elements including two kappaB sites. In the current study, binding and activity of the two kappaB elements in each putative allele were assessed by electrophoretic mobility shift and supershift assays. Functional activity was determined using luciferase reporter assays. The kappaB1 and kappaB2 elements in AG1 bound NF-kappaB with similar affinity. In contrast, the kappaB1 element of AG2 bound NF-kappaB with a much higher affinity than AG-1 kappaB1 (a 30-fold increase), whereas kappaB2 did not bind. Mutagenesis analysis showed that the difference in binding intensities was due to two nucleotides in the 3' end of kappaB1. Similarly, failure of AG2 kappaB2 binding was a result of the last nucleotide in the 3' end that differed from the consensus; mutating this nucleotide to match the consensus reestablished binding. Functional activity of the two putative alleles also differed; AG1 luciferase activity was consistently lower than that of AG2. Mutating the last two nucleotides in the 3' end of AG1 kappaB1 resulted in increased luciferase activity to levels comparable to that of AG2. Overall, these results show that in vitro variations in the promoter region may influence transcription of Paan-AG.

Early pregnancy loss and neonatal deaths associated with Klebsiella pneumonia infection: a mini review of possible occupational health risk.

Recurrent pregnancy loss is a disease of grave psychological and economic concern. The etiology in the vast majority of the cases is unknown or at best poorly understood. Although Klebsiella pneumonia infections have been reported in humans and animals during pregnancy, there is hardly any information to indicate whether or not these infections may be responsible for early pregnancy loss. We present a review of literature and report for the first time in humans, Klebsiella pneumonia infection in placenta of a 38-year-old secondary recurrent aborter (parity 2 + 3).

Intravenous immunoglobulin (IVIG): modes of action in the clinical management of recurrent pregnancy loss (RPL) and selected autoimmune disorders.

Recurrent pregnancy loss has been associated with autoimmune responses to membrane phospholipids and alloimmune reactions against paternally derived molecules on the trophoblast. The problem is psychologically and economically stressful as it undermines the capacity of some couples to reproduce and participate effectively in the day-to-day economic activities. This article reviews the adoption of intravenous immunoglobulin as a form of therapy for the clinical management of recurrent pregnancy loss and of selected autoimmune disorders. Side effects, contraindications and safety of use are discussed.

Management of stage I cervical sarcoma botryoides in childhood and adolescence.

UNLABELLED: Rhabdomyosarcomas are the most common soft tissue sarcomas in childhood. The botryoid variant arises in infancy from the vagina or urinary bladder and extremely rarely from the uterine cervix. Treatment regimes range from local excision of the tumour to radical hysterectomy with adjuvant multidrug therapy and/or radiotherapy. In cases of minimal cervical invasion, the less invasive local excision in combination with adjuvant chemotherapy has resulted in excellent survival rates with complete functional preservation of the bladder, rectum, vagina, and ovaries. We present here a 30-year literature review and a case report of a cervical sarcoma botryoides in a 5-year-old girl. CONCLUSION: based on the literature review and our own observation, we recommend minor surgical approaches in combination with chemotherapy as the treatment of choice for early stage I cervical rhabdomyosarcoma.