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Biomedical subjects

C Albert

Publications and source records attributed to C Albert.

At least 37 records · Page 2Linked to original sources
PubMed2000

The pathophysiology of endometriosis-associated infertility: follicular environment and embryo quality.

Several retrospective analyses of IVF and oocyte donation programmes, performed to gain clinical knowledge of the factors implicated in the aetiology of endometriosis-associated infertility, have demonstrated that the quality of the embryo is affected in patients with endometriosis. To understand the mechanisms of this alteration, the endocrine, paracrine and autocrine conditions induced during folliculogenesis in women with and without endometriosis were investigated. The first approach was to study ovarian steroid secretion in women undergoing IVF. Progesterone concentrations in follicular fluid increased with the severity of the disease and an increase in progesterone accumulation in vitro was observed in basal and hCG-stimulated granulosa cell cultures. It is proposed that the pattern of progesterone secretion may be related to changes in the release of cytokines by ovarian and white blood cells. Hence, a second trial measured interleukin 1 (IL-1), IL-6 and vascular endothelial growth factor (VEGF) concentrations in serum, follicular fluid and granulosa cell cultures. IL-6 concentrations in serum were higher in the natural cycles of women with endometriosis than in women in the control group, and were modulated by ovarian stimulation, decreasing significantly in serum from stimulated cycles. In addition, IL-6 concentrations were higher in the follicular fluid of women with endometriosis than in those in the control group and IL-6 was released in higher amounts by granulosa luteal cells of patients with endometriosis. VEGF was accumulated in lower concentrations in the follicular fluid of patients with endometriosis. These observations indicate that infertility in patients with endometriosis may be related to alterations within the follicle which, in turn, result in oocytes and embryos of lower quality, as demonstrated in the IVF programme. In addition, these embryos have a reduced ability to implant, as observed in the oocyte donation model. These alterations may be induced by functional changes in the process of folliculogenesis that affect steroid synthesis, as well as by cytokine release by ovarian and blood cells.

Embryo Transfer↗
PubMed2000

Effects of batroxobin on spatial learning and memory disorder of rats with temporal ischemia and the expression of HSP32 and HSP70.

The effect of Batroxobin on spatial memory disorder of left temporal ischemic rats and the expression of HSP32 and HSP70 were investigated with Morri's water maze and immunohistochemistry methods. The results showed that the mean reaction time and distance of temporal ischemic rats in searching a goal were significantly longer than those of the sham-operated rats and at the same time HSP32 and HSP70 expression of left temporal ischemic region in rats was significantly increased as compared with the sham-operated rats. However, the mean reaction time and distance of the Batroxobin-treated rats were shorter and they used normal strategies more often and earlier than those of ischemic rats. The number of HSP32 and HSP70 immune reactive cells of Batroxobin-treated rats was also less than that of the ischemic group. In conclusion, Batroxobin can improve spatial memory disorder of temporal ischemic rats; and the down-regulation of the expression of HSP32 and HSP70 is probably related to the attenuation of ischemic injury.

Animals↗
PubMed1999

Cellular localization of cyclo-oxygenase isozymes in Crohn's disease and colorectal cancer.

Deregulation of cyclo-oxygenase isozyme expression has been shown to be a consistent feature of inflammatory bowel diseases and colorectal cancer in humans. This study investigated the cellular localization of aberrant cyclo-oxygenase expression in normal and diseased colon. Biopsies of seven normal colonic tissues, eight tissue samples from patients suffering from Crohn's disease, five polyps from patients with familiar adenomatous polyposis coli, and ten sporadic adenocarcinomas were analyzed using isozyme-selective immunoprecipitation, western blotting, and immunohistochemistry. Cyclo-oxygenase-1 expression was demonstrated in normal human colon, Crohn's disease, and colorectal tumors. In normal colon and also in adenomatous polyps, cyclo-oxygenase-1 specific immunosignals were localized to epithelial cells of the upper part of the crypts and endocrine cells of the lower part. In Crohn's disease cyclo-oxygenase-1 expression was restricted to cells of the inflammatory infiltrate. While barely detectable in normal colon, cyclo-oxygenase-2 protein was strongly increased in epithelial cells located in the uppermost part of the crypts, in surface epithelial cells, and in mononuclear cells of the lamina propria of Crohn's disease. The constitutive overexpression of cyclo-oxygenase-2 protein observed in the majority of the adenomatous polyps and all adenocarcinomas was attributed to both epithelial and interstitial cells in that the latter predominated in adenomas, and epithelial cells were the prevailing cyclo-oxygenase-2 expressing cell type in adenocarcinomas. In conclusion, both autocrine and paracrine effects of aberrant cyclooxygenase-2 expression may contribute to the development of Crohn's disease and colonic tumor development.

Adenocarcinoma↗
PubMed1999

The pathogenesis of ovarian hyperstimulation syndrome: in vivo studies investigating the role of interleukin-1beta, interleukin-6, and vascular endothelial growth factor.

OBJECTIVE: To evaluate systemic and ovarian changes in levels of interleukin (IL)-1beta, IL-6, and vascular endothelial growth factor (VEGF) in response to hCG administration to determine which may be the potential initiator of vascular effects and to identify the main source of the substance; to evaluate serum and follicular fluid levels of these cytokines as markers of ovarian hyperstimulation syndrome (OHSS), and to compare levels of these cytokines under basal conditions in women with normal ovulation and those with polycystic ovary syndrome (PCOS). DESIGN: Prospective controlled study. SETTING: In vitro fertilization program at the Instituto Valenciano de Infertilidad, Valencia, Spain. PATIENT(S): Women undergoing IVF, in whom the first two study objectives were analyzed, and women with normal ovulation and patients with PCOS undergoing retrieval of immature oocytes in natural cycles or cycles stimulated for IUI but cancelled during induction of ovulation, in whom the third study objective was analyzed. INTERVENTION(S): Serum was collected before and after hCG administration, and follicular fluid was collected at ovum pick-up. MAIN OUTCOME MEASURE(S): Serum and follicular fluid levels of IL-1beta, IL-6, and VEGF. RESULT(S): There was a significant increase in serum VEGF levels after hCG administration in patients who were at risk for OHSS compared with those who were not at risk for OHSS. Significantly lower VEGF levels were found in the follicular fluid of patients who were at risk; this decrease was the only useful marker to discriminate between the two groups. Moreover, both groups had similar cytokine production under basal conditions. An increase in serum E2 occurred coincident with a decrease in IL-1beta, IL-6, and VEGF in patients with PCOS. CONCLUSION(S): Vascular endothelial growth factor seems to be the mediator of hCG on the vascular tree. There was an early systemic increase in VEGF that may have significance in the development of OHSS. A decrease in the follicular fluid VEGF concentration is a valid marker to identify women in whom OHSS will develop. The pattern of cytokine release in patients with PCOS under basal conditions was not different from that in women with normal ovulation.

Chorionic Gonadotropin↗
PubMed1999

Cytokines in older patients undergoing in vitro fertilization: the relationship to the response to controlled ovarian hyperstimulation.

PURPOSE: Our purpose was to assess the endocrine, autocrine, and paracrine milieu in follicles of older women undergoing stimulated cycles, comparing normal (NR) and low (LR) responses, based on the measurement of interleukin (IL)-1 beta, IL-6, and vascular endothelial growth factor (VEGF) in serum and follicular fluid (FF). METHODS: A total of 40 women entered the study, divided into three groups: (1) older patients (> 37 years) with NR (age-NR; n = 18); (2) older women with LR (age-LR; n = 11); and (3) normal controls, aged < 35 years (control; n = 11). IL-1 beta, IL-6, and VEGF measured in serum (day of ovum pickup) and FF, employing ELISAs. RESULTS: Follicular fluid IL-6 was significantly (P < 0.05) higher in age-LR compared to the other two groups. IL-6 and VEGF showed a 4- to 20-fold increase in FF compared to blood, suggesting the ovary as an additional source of both cytokines. IL-1 beta levels remained unchanged in FF compared to blood and, also, among groups. CONCLUSIONS: These data provide further evidence that the endocrine, paracrine, and/or autocrine status in vivo of older patients is different from that of younger women and suggest that cytokines, specifically IL-6, may be involved in the changes observed during senescence within the ovary.

Adult↗
PubMed1999

Comparison of expression and regulation of the high-density lipoprotein receptor SR-BI and the low-density lipoprotein receptor in human adrenocortical carcinoma NCI-H295 cells.

In rodents, cholesterol for adrenal steroidogenesis is derived mainly from high-density lipoproteins (HDL) via the HDL receptor, scavenger receptor-BI (SR-BI). In humans cholesterol for steroidogenesis is considered to be derived from the low-density lipoprotein (LDL) receptor pathway, and the contribution of SR-BI to that is unknown. In the present study SR-BI expression and regulation by steroidogenic stimuli was analysed in human adrenocortical cells and compared with LDL receptor expression. In addition, the functional contribution of both receptors for cholesteryl ester delivery to human adrenocortical cells was compared. Northern blot and reverse transcription-PCR amplification and sequence analysis demonstrated the presence of SR-BI mRNA in foetal and adult human adrenal cortex. Furthermore, SR-BI mRNA was expressed to similar levels in human primary adrenocortical and adrenocortical carcinoma NCI-H295 cells, indicating its presence in the steroid-producing cells. Treatment of NCI-H295 cells with 8Br-cAMP, a stimulator of glucocorticoid synthesis via the protein kinase A second messenger signal transduction pathway, resulted in an increase of both SR-BI and LDL receptor mRNA levels in a time- and dose-dependent manner. The induction of SR-BI and LDL receptor by cAMP was independent of ongoing protein synthesis and occurred at the transcriptional level. Ligand blot experiments indicated that a protein of similar size to SR-BI is the major HDL-binding protein in NCI-H295 cells. Western blot analysis demonstrated that cAMP treatment increased the levels of LDL receptor and, to a lesser extent, SR-BI protein in NCI-H295 cells. Binding and uptake of cholesterol was quantitatively smaller from HDL than from LDL, both in basal as well as in cAMP-stimulated cells. Scatchard analysis under basal conditions indicated that NCI-H295 cells express twice as many specific binding sites for LDL than for HDL. Dissociation constant values (Kd; in nm) were approximately five times higher for HDL than for LDL, indicating a lower affinity of HDL compared with LDL. The combined effects of these two parameters and the low cholesteryl ester content of HDL subfraction 3 (HDL3) contributes to a lower cholesteryl ester uptake from HDL than from LDL by the NCI-H295 cells. In conclusion, both the SR-BI and LDL receptor genes are expressed in the human adrenal cortex and coordinately regulated by activators of glucocorticoid synthesis. In contrast to rodents, in human adrenocortical cells the HDL pathway of cholesterol delivery appears to be of lesser importance than the LDL pathway. Nevertheless, the SR-BI pathway may become of major importance in conditions of functional defects in the LDL receptor pathway.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1999

Social support and chronic fatigue syndrome.

The role of social support was examined in Chronic Fatigue Syndrome (CFS). Social support has been shown to affect illness outcome in medical disorders, likely due in part to communication between patient and support giver on illness-related concerns. Forty-one participants, 25 of whom had a primary support giver, completed the Beck Depression Inventory, the Perceived Stress Scale, the Profile of Mood States, and the Inventory of Socially Supportive Behaviors (ISSB); the primary support giver completed a modified version of the ISSB indicating the level of support he or she provided and a questionnaire assessing beliefs about CFS. Results indicated that there were no differences among individuals with CFS with or without support on measures of mood and perceived stress. Individuals with CFS and their support givers agreed on the amount of support offered, and extent of support was independent of beliefs concerning etiology. Exploratory analyses revealed that verbal emotional-cognitive support generally was more predictive of mental health than was tangible, less communicative support. The lack of positive effect of social support is discussed in relation to the degree of support offered, and implications for future research are discussed.

Journal Article↗
PubMed1999

The monkey and human uridine diphosphate-glucuronosyltransferase UGT1A9, expressed in steroid target tissues, are estrogen-conjugating enzymes.

Considering the physiologic importance of the steroid response, which is regulated in part by steroid levels in a given tissue, relatively little is known about steroid glucuronidation, which is widely accepted as a major pathway involved in the catabolism and elimination of steroid hormones from the human body. In a previous study, it was ascertained that the monkey may be the most appropriate model in which to examine the role of steroid glucuronidation. Northern blot analysis of simian RNA, hybridized with human UGT complementary DNA (cDNA) probes demonstrate the similarity of the transcripts. The simian UGT1A09 cDNA isolated from a liver library is 2396 bp and contains an open reading frame encoding 530 amino acids. The predicted primary structure is most homologous to the human UGT1A9 (hUGT1A9) enzyme, which share 93% identity. Stable transfection of the monkey UGT1A09 (monUGT1A09) cDNA into HK293 cells, expresses a microsomal protein with an apparent molecular mass of 55 kDa. Of the more than 30 endogenous substrates tested, both proteins show the highest activity on 4-hydroxyestradiol and 4-hydroxyestrone, followed by 2-hydroxyestradiol and estradiol. RT-PCR analysis demonstrate that UGT1A9 transcript is expressed in several tissues, which include the prostate, testis, breast, ovary, and skin of the monkey and humans. The expression of UGT1A9 in extrahepatic estrogen-responsive tissues, and its high activity on estrogens is consistent with this enzyme having a role in estrogen metabolism.

Amino Acid Sequence↗
PubMed1998

The follicular endocrine environment in stimulated cycles of women with endometriosis: steroid levels and embryo quality.

OBJECTIVE: To assess the endocrine milieu in follicles of stimulated cycles comparing women with and without endometriosis. Steroids were measured in follicular fluid (FF) and in in vitro culture of granulosa-luteal cells, and this status was related to the quality of the embryos obtained after IVF. DESIGN: Case-control study. SETTING: IVF program at the Instituto Valenciano de Infertilidad. PATIENT(S): Twenty-four women with laparoscopically documented endometriosis and 26 controls undergoing IVF. INTERVENTION(S): Individual follicular aspiration, oocyte isolation, FF storage, and preparation of luteinized granulosa cells for culture; oocyte insemination and embryo cleavage in standard IVF. MAIN OUTCOME MEASURE(S): Serum (day of ovum pickup) and FF measurements of estradiol, progesterone, testosterone, and androstenedione. Secretion of progesterone was measured in the cell-conditioned medium. Results were compared between patients with endometriosis and controls, as well as between oocytes that yielded embryos of different quality. RESULT(S): Levels of progesterone in the FF increased with the severity of the disease, whereas testosterone accumulation in the FF decreased with the severity of the disease. An increase in progesterone accumulation in vitro was observed in basal and hCG-induced granulosa cell cultures. No difference was observed in terms of embryo quality, and no steroid marker was able to identify follicles with oocytes that displayed embryos of good or bad quality under the inverted microscope. CONCLUSION(S): The data show differences in the steroidogenesis of follicles from stimulated women with and without endometriosis. These changes indicate good endocrine health but are not predictive of embryo quality.

Adult↗
PubMed1998

The follicular and endocrine environment in women with endometriosis: local and systemic cytokine production.

OBJECTIVE: To assess the endocrine, paracrine, and autocrine milieu in patients with endometriosis on the basis of the measurement of several cytokines in serum and follicular fluid (FF) and in vitro culture of granulosa luteal cells. DESIGN: Case-control study. SETTING: In vitro fertilization program at the Instituto Valenciano de Infertilidad. PATIENT(S): Twenty patients with laparoscopically documented endometriosis and 18 controls. Fifteen subjects were studied in a natural cycle and 23 were investigated in a stimulated cycle while undergoing IVF. INTERVENTION(S): Individual follicle aspiration, oocyte isolation, FF storage, and preparation of luteinized granulosa cell cultures. Diagnostic laparoscopy in natural cycles. MAIN OUTCOME MEASURE(S): Serum (day of ovum pick-up or laparoscopy) and FF measurement of interleukin (IL)-1beta, IL-6, and vascular endothelial growth factor (VEGF). Secretion of IL-1beta, IL-6, and VEGF in the cell-conditioned medium. Results were compared between patients with endometriosis and controls. RESULT(S): Interleukin-6 levels in serum were increased in the natural cycles of patients with endometriosis and modulated by ovarian stimulation, showing a significant decrease in hMG- and FSH-stimulated cycles and a significant increase after hCG administration. In addition, IL-6 levels were increased in the FF of patients with endometriosis and released in higher amounts by their granulosa luteal cells. Vascular endothelial growth factor was accumulated in lesser concentrations in the FF of patients with endometriosis. Interleukin-1beta levels did not show significant changes. Implantation rates were decreased significantly in patients with endometriosis who were undergoing IVF. CONCLUSION(S): The data demonstrate that cytokines are regulated differently in patients with endometriosis, who have increased IL-6 production, and suggest that fine hormonal modulation of this cytokine occurs at the systemic and local (ovarian) levels. These changes show that the endocrine, paracrine, and autocrine milieu is different in patients with endometriosis and may be related to their lower implantation rates.

Adult↗
PubMed1998

Ovarian follicular dynamics: from basic science to clinical practice.

The management of low responders (LR) to ovarian stimulation in cycles of assisted reproduction (AR) is a difficult challenge. Aging of the ovary and LR are coincidental in many situations, but LR is also present in young patients undergoing AR. In fact, today it is a recognized cause of infertility. When the aged ovary is considered, there is evidence that the functioning of the granulosa cells as well as the quality of the oocytes and resulting embryos are affected. Similarly, in young LR, the production of inhibin is affected. However, there is no evidence that the quality of the oocyte and/or the resulting embryo is affected. In this study, we have retrospectively analyzed our files and observed that the quality of the oocytes and embryos was similar between younger and older LR and normal responders (NR). Studies using color Doppler vaginal ultrasound have shown that the pulsatility index (PI) and the resistance index (RI) were increased in LR as compared with NR, suggesting that there was some degree of vascular resistance to flow. Treatment of LR is also a difficult challenge. Ovum donation is a successful treatment for LR, since cumulative birth rates are > 85% with four attempts of embryo transfer. The future may be promising for LR once new technologies are introduced into clinical practice. The use of recombinant gonadotropins and genetically engineered human gonadotropin derivatives may be of considerable help for LR. Similarly, non-gonadotropin hormones, such as cytokines or growth factors, may be shown to play a role in the stimulation of the ovary in the near future, and may therefore open new frontiers for treatment of LR.

Aging↗
PubMed1997

Biological variability in the structures of diphosphoinositol polyphosphates in Dictyostelium discoideum and mammalian cells.

Previous structural analyses of diphosphoinositol polyphosphates in biological systems have relied largely on NMR analysis. For example, in Dictyostelium discoideum, diphosphoinositol pentakisphosphate was determined by NMR to be 4- and/or 6-PPInsP5, and the bisdiphosphoinositol tetrakisphosphate was found to be 4, 5-bisPPInsP4 and/or 5,6-bisPPInsP4 [Laussmann, Eujen, Weisshuhn, Thiel and Vogel (1996) Biochem. J. 315, 715-720]. We now describe three recent technical developments to aid the analysis of these compounds, not just in Dictyostelium, but also in a wider range of biological systems: (i) improved resolution and sensitivity of detection of PPInsP5 isomers by microbore metal-dye-detection HPLC; (ii) the use of the enantiomerically specific properties of a rat hepatic diphosphatase; (iii) chemical synthesis of enantiomerically pure reference standards of all six possible PPInsP5 isomers. Thus we now demonstrate that the major PPInsP5 isomer in Dictyostelium is 6-PPInsP5. Similar findings obtained using the same synthetic standards have been published [Laussmann, Reddy, Reddy, Falck and Vogel (1997) Biochem. J. 322, 31-33]. In addition, we show that 10-25% of the Dictyostelium PPInsP5 pool is comprised of 5-PPInsP5. The biological significance of this new observation was reinforced by our demonstration that 5-PPInsP5 is the predominant PPInsP5 isomer in four different mammalian cell lines (FTC human thyroid cancer cells, Swiss 3T3 fibroblasts, Jurkat T-cells and Chinese hamster ovary cells). The fact that the cellular spectrum of diphosphoinositol polyphosphates varies across phylogenetic boundaries underscores the value of our technological developments for future determinations of the structures of this class of compounds in other systems.

3T3 Cells↗
PubMed1996

Expression and regulation of the lipoprotein lipase gene in human adrenal cortex.

Lipoprotein lipase (LPL), an enzyme which hydrolyzes triglycerides and participates in the catabolism of remnant lipoproteins, plays a crucial role in energy and lipid metabolism. The goal of this study was to analyze the expression and regulation of the LPL gene in human adrenals. Reverse transcriptase-polymerase chain reaction amplification and sequence analysis demonstrated the presence of LPL mRNA in fetal and adult human adrenal cortex. Furthermore, the human adrenocortical carcinoma cell line, NCI-H295, expresses LPL mRNA and protein, which is localized to the outer cellular membrane as demonstrated by immunofluorescence confocal microscopy and can be released in the medium by heparin addition. To asses whether the LPL gene is regulated by agents regulating adrenal steroidogenesis, NCI-H295 cells were treated with activators of second messenger systems. Whereas the calcium-ionophore A23187 did not affect LPL gene expression, treatment with phorbol 12-myristate 13-acetate decreased LPL mRNA levels in a time- and dose-dependent manner. This decrease after phorbol 12-myristate 13-acetate was associated with diminished heparin-releasable LPL mass and activity in the culture medium. Addition of the cAMP analog 8-Br-cAMP to NCI-H295 cells resulted in a rapid, but transient dose-dependent induction of LPL mRNA. Treatment with the protein synthesis inhibitor cycloheximide gradually induced, whereas simultaneous addition of cAMP and cycloheximide superinduced LPL mRNA levels. Nuclear run-on analysis indicated that the effects of cAMP and cycloheximide occurred at the transcriptional and post-transcriptional level, respectively. Transient co-transfection assays demonstrated that the first 230 base pairs of the proximal LPL promoter contain a cAMP-responsive element activated by protein kinase A and transcription factors belonging to the CREB/CREM family. These data indicate that LPL is expressed in human adrenal cortex and regulated in NCI-H295 adrenocortical carcinoma cells by activators of the protein kinase A and protein kinase C second messenger pathways in a manner comparable to P450scc, which catalyzes the first step in adrenal steroidogenesis. These observations suggest a role for LPL in adrenal energy and/or lipid metabolism and possibly in steroidogenesis.

8-Bromo Cyclic Adenosine Monophosphate↗