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Biomedical subjects

Michael P Diamond

Publications and source records attributed to Michael P Diamond.

At least 19 recordsLinked to original sources
PubMed2007

Reconstruction of ooplasm recipient oocytes with frozen-thawed donor microcytoplasts and influence on the microtubular spindle.

OBJECTIVE(S): To cryopreserve micromanipulated ooplast segments (microcytoplasts) from mouse oocytes, compare microcytoplast and parent or recipient oocyte fusion performed within or without the zona pellucida, compare electrofusion of fresh or frozen oocyte with frozen-thawed microcytoplasts, and assess spindle integrity after reconstruction of oocytes. DESIGN: Prospective experimental study. SETTING: University-based experimental laboratory. ANIMAL(S): Mouse (MII) oocytes obtained after superovulation (n = 363). INTERVENTION(S): Micromanipulation of oocytes (n = 363) into microcytoplasts (n = 181), cryopreservation of microcytoplasts along with parent and sibling control oocytes (n = 182), reconstruction by electrofusion of microcytoplast and parent or recipient oocyte performed with (group A, n = 35) or without a zona pellucida (group B, n = 32), comparison of electrofusion of fresh oocyte (group C, n = 40) or frozen oocyte (group D, n = 36) with frozen-thawed microcytoplasts fused within zona, and assessment of spindle morphology of reconstructed oocyte. MAIN OUTCOME MEASURE(S): Post-thaw survival, success of fusion, and spindle integrity as assessed by immunostaining. RESULT(S): Higher success of post-thaw fusion was seen in group A (91.4%) compared with group B (56.2%). The post-thaw fusion of microcytoplasts with either fresh or frozen oocytes was not significantly different. Spindle integrity was 82.5% in group C as compared with 47.2% in group D. CONCLUSION(S): Microcytoplasts created from oocytes can be successfully cryopreserved, thawed, and used to reconstruct oocytes with intact spindles.

Animals↗
PubMed2007

Ambient manganese exposure is negatively associated with human sperm motility and concentration.

BACKGROUND: Occupational and experimental animal studies indicate that exposure to high levels of manganese impairs male fertility, but the effects of ambient manganese in humans are not known. METHODS: We measured blood levels of manganese and selenium in 200 infertility clinic clients in a cross-sectional study. Correlations between metals and semen variables were determined, adjusting for other risk factors. Outcomes were low motility (<50% motile), low concentration (<20 million/mL), or low morphology (<4% normal). We also investigated dose-response relationships between quartiles of manganese exposure and sperm parameters. RESULTS: High manganese level was associated with increased risk of low sperm motility (odds ratio = 5.4; 95% confidence interval = 1.6-17.6) and low sperm concentration (2.4; 1.2-4.9). We saw a U-shaped dose-response pattern between quartiles of manganese exposure and all 3 sperm parameters. CONCLUSION: Ambient exposure to manganese levels is associated with a reduction in sperm motility and concentration. No adverse effects were seen for high selenium.

Adult↗
PubMed2006

Modulation of the expression of peroxisome proliferators-activated receptors in human fibroblasts.

To determine the levels of peroxisome proliferators-activated receptors (PPARs) in normal and adhesion fibroblasts, we utilized real-time reverse transcription-polymerase chain reaction to measure messenger RNA (mRNA) levels in fibroblasts from normal peritoneum and adhesions from five patients in both the presence or absence of dichloroacetic acid (DCA) and a cyclooxygenase-2 (COX-2) inhibitor, NS-398. Peroxisome proliferators-activated receptor alpha, PPARbeta, PPARgamma1, and PPARgamma2 mRNA are all present in normal peritoneal and adhesion fibroblasts, and selectively rose in response to hypoxia and either DCA or NS-398.

Cyclooxygenase 2 Inhibitors↗
PubMed2006

Utility of screening for other causes of infertility in women with "known" polycystic ovary syndrome.

We investigated the prevalence of abnormal screening results (questionnaire and testing for other causes of oligo-ovulation, male or tubal factor infertility) in a group of 1,313 oligo-ovulatory women (included and excluded subjects) whose condition was screened for inclusion in the Pregnancy in Polycystic Ovary Syndrome trial, a multicenter clinical trial that was conducted at 13 sites in the United States. Other than failure to demonstrate laboratory evidence of hyperandrogenemia, the most common reasons for subject exclusion were persistent oligospermia and tubal factor infertility.

Causality↗
PubMed2006

Altered in vitro immune response to hypoxia-treated normal peritoneal fibroblasts.

Hypoxia treatment of normal peritoneal fibroblasts results in alterations that are characteristic for fibroblasts obtained from postoperative peritoneal adhesion tissue. In this study, we have shown that hypoxia treatment enhances normal peritoneal fibroblast elimination by lymphokine-activated killer cells to the level of adhesion tissue fibroblasts, suggesting a pivotal role of hypoxia in the adhesion development.

Adaptation, Physiological↗
PubMed2006

Activation of the cGMP signaling pathway is essential in delaying oocyte aging in diabetes mellitus.

Uncontrolled diabetes mellitus (DM) adversely affects oocyte maturation and embryo development via mechanisms that are yet unclear. Nonetheless, DM may cause uncoupling of nitric oxide synthases (NOSs) with reduction in the bioavailability of nitric oxide (NO), which is critical to maintain oocyte viability and prevent aging. The current study investigates the role of NO-mediated signaling related to oocyte aging in diabetic and nondiabetic mice. Age-related alterations in the oocytes, including ooplasmic microtubule dynamics (OMD), cortical granule (CG) status, and zona pellucida (ZP) hardening as well as the integrity of the spindle/chromatin were studied using confocal microscopy. Oocytes obtained from diabetic mice exhibited accelerated aging compared to that from nondiabetic mice. Moreover, oocytes from diabetic animals were exquisitely sensitive to NOS and guanylate cyclase (GC) inhibitors (L-NAME, ODQ), which induced aging and relatively resistant to its delay by the cGMP derivative (8-Br-cGMP). Oocytes from nondiabetic control mice displayed similar sensitivity to L-NAME in older oocytes, although to a significantly lower extent than that of DM (P < 0.04-0.0001). Despite the differences in response between DM and nonDM mice, the activation of cGMP pathway is essential to maintain the integrity of oocytes and delay oocyte aging. These findings not only indicate the role of NO signaling in the prevention of oocyte aging but also suggest enhanced aging and NO insufficiency in oocytes from diabetic mice. A comprehensive model incorporating our current findings with NOS, GC, and G kinase cycles is presented.

Animals↗
PubMed2006

The Pregnancy in Polycystic Ovary Syndrome study: baseline characteristics of the randomized cohort including racial effects.

OBJECTIVE: To report the baseline characteristics and racial differences in the polycystic ovary syndrome (PCOS) phenotype from a large multicenter clinical trial (PPCOS). DESIGN: Double-blind, randomized trial of three treatment regimens (with extended release metformin or clomiphene citrate). SETTING: Academic medical centers. PATIENT(S): Six hundred twenty-six infertile women with PCOS, aged 18-39 years, with elevated T levels and oligomenorrhea (exclusion of secondary causes), seeking pregnancy, with > or = 1 patent fallopian tube, normal uterine cavity, and a partner with sperm concentration > or = 20 x 10(6)/mL in > or = 1 ejaculate. INTERVENTION(S): Baseline characterization. MAIN OUTCOME MEASURE(S): Historical, biometric, and biochemical measures of PCOS. RESULT(S): There were no significant differences in baseline variables between treatment groups. The overall mean (+/-SD) age of the subjects was 28.1 +/- 4.0 years, and the mean body mass index was 35.2 kg/m2 (+/-8.7). Polycystic ovaries (PCOs) were present in 90.3% of the subjects, and the mean volume of each ovary was 10 cm3 or more. Of the subjects, 7% had ovaries that were discordant for PCO morphology. At baseline, 18.3% of the subjects had an abnormal fasting glucose level (> 100 mg/dL). Asians tended to have a milder phenotype, and whites and African Americans were similar in these measures. CONCLUSION(S): The treatment groups were well matched for baseline parameters, and we have added further information to the PCOS phenotype.

Adolescent↗
PubMed2006

Effects of hyperglycemia on the differential expression of insulin and insulin-like growth factor-I receptors in human normal peritoneal and adhesion fibroblasts.

OBJECTIVE: To determine whether the insulin receptor (IR), insulin-like growth factor-I receptor (IGF-IR), and IGF-I are expressed differentially in fibroblasts isolated from normal peritoneal and adhesion tissue before and after 24-hour treatment with increasing glucose concentrations. DESIGN: Prospective experimental study. SETTING: University medical center. PATIENT(S): Primary cultures of fibroblasts established from peritoneal and adhesion tissues of the same patients. INTERVENTION(S): Glucose treatment of the primary cultured fibroblasts for 24 hours with increasing concentrations of glucose (100-850 mg/dL). MAIN OUTCOME MEASURE(S): Real-time polymerase chain reaction was used to measure messenger RNA (mRNA) levels for IR, IGF-IR, and IGF-I. Enzyme-linked immunosorbent assay was used to determine protein levels. RESULT(S): At the normal glycemic level (100 mg/dL), adhesion fibroblasts have significantly higher mRNA levels of the IR (7.96 +/- 0.15 vs. 6.97 +/- 0.16; P<.05), IGF-IR (7.72 +/- 0.22 vs. 6.88 +/- 0.06; P<.05), and IGF-I (7.04 +/- 0.10 vs. 5.92 +/- 0.10; P<.05) when compared with normal fibroblasts, respectively. Data are expressed as log(mRNA/microg RNA). Normal fibroblasts respond to increasing glucose concentrations by increasing the expression levels of the IR, IGF-IR, and IGF-I, whereas adhesion fibroblasts respond by decreasing the expression of the IR, IGF-IR, and IGF-I. CONCLUSION(S): The differential expression of the IR, IGF-IR, and IGF-I in adhesion fibroblasts may contribute to the pathogenesis of fibrosis observed in diabetic patients.

Cells, Cultured↗
PubMed2006

Female infertility and free radicals: potential role in adhesions and endometriosis.

Free radicals are highly reactive molecules produced in the cell either as part of, or as end-products of, biochemical reactions that have crucial roles in the homeostasis of the organism. Thus, excess production or impaired elimination of free radicals leads to increased oxidative stress, which has been implicated in the development of several different disease states, including hypoxia-reperfusion injury, cancer, and aging. Peritoneal adhesions and endometriosis are relatively commonly identified in women, and are known to be associated with infertility without clearly understood pathophysiology. The prevention and treatment strategies of these conditions, both of which have tremendous propensity to recur, have not been completely established. The development of both disorders has been shown to be closely related to the presence of increased oxidative stress in the tissues. In this article, we review this relationship with reference to the mechanistic steps involved and their regulation. As our knowledge of both conditions expands, we believe there will be opportunities for specific steps to intervention in free radical metabolism to reduce and/or prevent further development of endometriosis and adhesions.

Endometriosis↗
PubMed2006

First-trimester Doppler investigation of the uterine circulation.

There is now strong evidence that fetal events can significantly impact postnatal health and disease development. Doppler velocimetry can identify some early pathologic changes in pregnancy. Many investigators have tried to delineate the normal and pathologic models of the uterine circulation in the first trimester, but much has yet to be defined. A discrete amount of confusion derives from the incomplete knowledge of the initial placental development, and particularly the development of the intervillous circulation. This article comprehensively reviews the literature on first-trimester Doppler in both normal and complicated pregnancies, and briefly discusses potential future areas of application.

Blood Flow Velocity↗
PubMed2006

The effect of dystocia and previous cesarean uterine scar on the tensile properties of the lower uterine segment.

OBJECTIVE: The remodeling of uterine connective tissue during labor can lead to the reorganization of the extracellular matrix that, in turn, may influence the biomechanical properties of the myometrial wall. We hypothesized that the stretching of the lower uterine segment in laboring women with dystocia changes the viscoelastic properties of the uterine wall. STUDY DESIGN: We tested the tensile strength of lower uterine segment myometrium in 68 pregnant women at term. The biomechanical, structural, and biochemical properties were compared among 3 groups: (1) 39 laboring women who underwent primary low-transverse cesarean delivery for labor dystocia, (2) 12 nonlaboring women who underwent primary elective low-transverse cesarean delivery and (3) 17 women who underwent an elective repeat low-transverse cesarean delivery at term. The tensile properties were quantitated with a stretching regimen that was designed to mimic the conditions of labor. Parameters such as slope, yield point, and break point were recorded, analyzed, and interpreted. Biochemical properties were determined by the measurement of the sulfated glycosaminoglycans, hydroxyproline, and pyridinoline-deoxypyridinoline. Histologic properties of the connective tissue were assessed by collagen birefringence. Lastly, the association between these properties and biomechanical responses were compared among groups. RESULTS: Lower uterine segment myometrium specimens obtained from laboring women were stiffer compared with specimens from women who were not in labor (P = .013) or had scarred myometrium (P < .001). The force that was required to reach the yield point was similar between labor and nonlabor groups (P = .216). Likewise, a previous lower uterine segment scar did not alter the yield point. The break point was similar among all groups (P = .317). Sulfated glycosaminoglycan levels were unaffected by labor or scarring (P = .354). Scarred lower uterine segment myometrium had a higher collagen content compared with unscarred myometrium specimens that were obtained during labor (P = .025). Although there were similar degrees of collagen cross-linking among groups (P = .212), there was lower collagen birefringence in myometrium from laboring women compared with nonlaboring women (P < .001). CONCLUSION: Labor alters the viscoelastic properties of myometrium. Lower uterine segment myometrium is stiffest in women with dysfunctional labor compared with nonlabor control subjects. Labor and scarring also alter the pattern of collagen birefringence. Similar collagen cross-linking among the study groups may explain the reason that the breaking strength of the tissue is not altered by the state of labor and the reason that the rupture of the uterine scar is a rare event.

Adult↗
PubMed2006

The effects of the inhibition of inducible nitric oxide synthase on angiogenesis of epithelial ovarian cancer.

OBJECTIVE: The release of nitric oxide by tumor cells, through the stimulation of inducible nitric oxide synthase expression, may play a critical role in ovarian cancer progression. In this study we have sought to determine the effects of inhibiting inducible nitric oxide synthase on angiogenesis that was induced by 2 ovarian cancer cell lines, SKOV and MDAH2774. STUDY DESIGN: Real-time polymerase chain reaction and enzyme-linked immunosorbent assay techniques were used to determine the expression levels of inducible nitric oxide synthase and vascular endothelial growth factor in the ovarian cancer cell lines in response to treatments with L-NAME, an inhibitor of nitric oxide synthase, and SNAP, and nitric oxide donor. Ovarian cancer-induced angiogenesis was assessed in vitro with an established assay that is based on the ability of human umbilical vein endothelial cells to form a tubular network in response to angiogenic agents. RESULTS: SKOV and MDAH2774 cell lines exhibited over-expression of inducible nitric oxide synthase and have high baseline nitric oxide levels. This was associated with high levels of vascular endothelial growth factor production and angiogenesis induction. Treatment of the ovarian cancer cell lines with L-NAME significantly reduced vascular endothelial growth factor levels production and completely inhibited angiogenesis. In contrast, treatment with SNAP significantly increased vascular endothelial growth factor levels and increased angiogenesis in both cell lines. CONCLUSION: Our data suggest that the inhibition of inducible nitric oxide synthase may form a basis for a novel therapeutic treatment option for ovarian cancer therapy.

Cell Line, Tumor↗
PubMed2006

The transcriptome of the uterine cervix before and after spontaneous term parturition.

OBJECTIVE: This study was designed to identify genes differentially expressed in the human uterine cervix after spontaneous term labor. STUDY DESIGN: The transcriptome of cervical tissue was characterized using Affymetrix HG-U133 plus 2 microarrays. Samples were collected from patients at term not in labor (n = 7) and after spontaneous labor (n = 9). Microarray statistical analysis included robust multiarray average, reduction of invariant probes, and permutation analysis for differential expression. Real-time quantitative reverse transcriptase-polymerase chain reaction assays of selected genes were performed on a new set of samples from term patients without labor (n = 10) and patients after spontaneous labor (n = 9). RESULTS: (1) The cervical transcriptome of term patients without labor was dramatically different from that of patients who underwent labor; (2) unique genes (n = 1192) were differentially expressed in the cervical tissue from patients after spontaneous labor, compared with that of the term patients without labor (false discovery rate less than 0.05, absolute fold change greater than 2); (3) Gene Ontology analysis indicated that multiple "Biological Process" categories were enriched, including "response to biotic stimulus," "apoptosis," "epidermis development," and "steroid metabolism"; (4) of major interest, genes involved in neutrophil chemotaxis were dramatically up-regulated in specimens from women after spontaneous labor; (5) real-time quantitative reverse transcriptase-polymerase chain reaction confirmed the increased expression of interleukin-8, interleukin-6, and vascular endothelial growth factor in patients after spontaneous labor; and (6) Toll-like receptor-3 and Toll-like receptor-5 showed decreased gene expression in patients after spontaneous labor. This was confirmed by real-time quantitative reverse transcriptase-polymerase chain reaction. CONCLUSION: (1) Cervical dilatation in term labor is associated with a stereotypic gene expression pattern determined by microarray, which is characterized by overexpression of genes involved in neutrophil chemotaxis, apoptosis, extracellular matrix regulation, and steroid metabolism; (2) Toll-like receptor-3 and Toll-like receptor-5 are differentially regulated during spontaneous parturition at term; and (3) this study provides an unbiased and comprehensive description of the changes in the cervical transcriptome before and after spontaneous term labor.

Adolescent↗
PubMed2006

Effects of interferon-gamma reverse hypoxia-stimulated extracellular matrix expression in human peritoneal and adhesion fibroblasts.

OBJECTIVE: To determine the response of adhesion and normal peritoneal fibroblasts to interferon-gamma (IFN-gamma) under normal and hypoxic conditions. DESIGN: Prospective experimental study. SETTING: University medical center. PATIENT(S): Primary cultures of fibroblasts established from peritoneal and adhesion tissue of the same patients. INTERVENTION(S): Hypoxia and IFN-gamma treatment of the primary cultured fibroblasts. MAIN OUTCOME MEASURE(S): Primary cultures of fibroblasts were established from peritoneal and adhesion tissues of the same patients (n = 5). The expression of extracellular matrix components (type I collagen and fibronectin) in adhesion and peritoneal fibroblasts under normal (20% O2) and hypoxic (2% O2) conditions was evaluated by multiplex reverse-transcription polymerase chain reaction analysis. RESULT(S): Adhesion fibroblasts (ADF) have increased basal levels of type I collagen as compared with normal peritoneal fibroblasts (NF). Interferon-gamma treatment resulted in a dose-response decrease in type I collagen and fibronectin mRNA levels in both ADF and NF. Hypoxia treatment resulted in a time-response increase in type I collagen and fibronectin mRNA levels in NF and ADF. Hypoxia had no effect on type I collagen and fibronectin mRNA levels in the presence of increasing dose of IFN-gamma in both NF and ADF. Interferon-gamma can block the stimulating effects of hypoxia on type I collagen expression, supporting the antifibrogenic nature of this cytokine. CONCLUSION(S): Understanding the mechanism by which IFN-gamma exerts its effect will be important in the utilization of this cytokine as a therapy for postoperative adhesion and tissue fibrosis.

Cell Adhesion↗
PubMed2006

Embryos generated using testicular spermatozoa have higher developmental potential than those obtained using epididymal spermatozoa in men with obstructive azoospermia.

OBJECTIVE: To determine whether the injection of testicular spermatozoa results in more viable embryos (higher implantation rate) than injection of epididymal spermatozoa in cases of obstructive azoospermia. DESIGN: Retrospective analysis of 265 cases of testicular sperm aspiration (TESA) and percutaneous sperm aspiration (PESA), including 185 cases of obstructive azoospermia. SETTING: Private Infertility clinic. PATIENT(S): None, charts review. INTERVENTION(S): None, charts review. MAIN OUTCOME MEASURE(S): Clinical pregnancy rate (PR), implantation rate. RESULT(S): Although fertilization rates were higher in the PESA group, implantation rates were significantly better in the TESA group. There was also a trend to higher ongoing PR and lower miscarriage rates in TESA cases. CONCLUSION(S): In cases of obstructive azoospermia, embryos generated using testicular spermatozoa have higher developmental potential than those obtained using epididymal spermatozoa.

Brazil↗
PubMed2006

Effect of oxidized regenerated cellulose (Interceed) on the expression of tissue plasminogen activator and plasminogen activator inhibitor-1 in human peritoneal fibroblasts and mesothelial cells.

OBJECTIVE: To characterize the molecular changes that occur in normal fibroblasts, adhesion fibroblasts, and mesothelial cells as a result of exposure to oxidized regenerated cellulose (Interceed; Johnson & Johnson Medical, Inc., New Brunswick, NJ). DESIGN: Control and Interceed-treated normal peritoneal fibroblasts, adhesion fibroblasts, and mesothelial cells in culture were assessed for messenger RNA levels of molecules known to be associated with adhesion development, using multiplex reverse transcriptase polymerase chain reaction (n = 4). SETTING: University research laboratory. PATIENT(S): Normal and adhesion fibroblasts and mesothelial cells. INTERVENTION(S): Exposure of cells, normal fibroblasts, adhesion fibroblasts, and mesothelial cells to oxidized regenerated cellulose. MAIN OUTCOME MEASURE(S): Real-time reverse transcriptase polymerase chain reaction expression of messenger RNA tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), and tPA-PAI-1 ratio, an indicator of overall fibrinolytic activity. RESULT(S): Interceed treatment of normal peritoneal fibroblasts, adhesion fibroblasts, and mesothelial cells results in an increased expression of tPA in mesothelial cells and an increase in the tPA-PAI-1 ratio, signifying an overall increase in fibrinolytic activity. CONCLUSION(S): Interceed, which has been shown in multiple human in vivo studies to decrease postoperative adhesion development, increases the expression of tPA and the tPA-PAI-1 ratio (an indicator of overall fibrinolytic activity), thereby promoting dissolution of fibrin and healing without adhesion development. Thus, the ability of Interceed to reduce postoperative adhesion development may be derived from both a barrier and biologic effect.

Cells, Cultured↗