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Biomedical subjects

B Gonik

Publications and source records attributed to B Gonik.

At least 37 records · Page 2Linked to original sources

In utero progression of isolated renal pelvis dilation.

The objective of this study to determine the risk of in uteroprogression of renal pelvis dilation when detected on antenatal ultrasound examination. We reviewed 230 fetuses with evidence of renal pelvis dilation. At least one exam was subsequently performed prior to delivery in all cases. Renal pelvis dilation was defined as an anterior-posterior renal pelvis measurement > 4 mm at < 32 weeks' and > 7 mm at > or = 32 weeks' gestation. Hydronephrosis was considered to be present when the renal pelvis measured +10 mm independent of gestational age. Multiple gestations and fetuses with additional congenital anomalies were excluded. The mean gestational age at diagnosis was 24 weeks. Renal pelvis dilation progressed to hydronephrosis in a total of 10.9% (25 of 230) of fetuses. There was a 3.3% chance of unilateral renal pelvis dilation progressing to hydronephrosis versus 26.0% in bilateral dilation (OR 10.4 [95% Cl 3.5-33.3]). Of those fetuses with progression, 80% had bilateral dilation (p < 0.0001). There was no difference in progression between right and left kidneys. Additionally, gender, gestational age at diagnosis and delivery, and birth weight did not differ between those fetuses with and without progression. The hydronephrosis in 7 of 25 (28%) regressed to pyelectasis on a subsequent ultrasound exam. Thus, the overall rate of progression of renal pelvis dilation to persistent hydronephrosis was 7.8% (18 of 230). In conclusion, the risk of isolated renal pelvis dilation progressing to hydronephrosis is low. Although bilateral pelvis dilation carries a higher risk for progression, no fetus in our study required in utero intervention. A follow up scan prior to delivery may be considered to identify those fetuses who will require postpartum intervention.

Adult↗

Characterization of the imprinted IPW gene: allelic expression in normal and tumorigenic human tissues.

IPW (Imprinted gene in the Prader-Willi syndrome region) is a recently identified paternally expressed gene. Previous work has demonstrated IPW expression in the human fetus and adult, with monoallelic expression in adult lymphoblasts and fibroblasts, and in fetal tissues. To further examine the expression of IPW, a series of experiments were carried out using RT-PCR to measure IPW expression in placentae and various fetal and tumor tissues. Biallelic expression of IPW was found in testicular germ cell tumor and bladder cancer cells, suggesting loss of imprinting in the latter case. Both H19 and Insulin-like growth Factor 2 (IGF2), two additional imprinted genes, also showed biallelic expression in those same tumors that demonstrated IPW biallelic expression. Of note, the naturally occurring parthenogenetic-derived mature teratoma unexpectedly expressed large amounts of IPW. Lastly, the pluripotent embryonal cancer cell line Tera-2 expressed IPW at the same level before and after differentiation induced by retinoic acid, suggesting that this gene functions in a 'housekeeping' capacity throughout cell growth. This was in contradistinction to H19 and IGF2, both of which showed significant transcriptional upregulation after Tera-2 cell differentiation.

Adult↗

Vulvar vestibulitis subjects undergoing surgical intervention: a descriptive analysis and histopathological correlates.

OBJECTIVE: We describe here a series of selected patients from an established vaginitis research clinic diagnosed with vulvovestibulitis (VV) who underwent surgical intervention for focal disease. Long-term results of surgical correction are reported and characteristic histopathology findings associated with vulvar vestibulitis are emphasized. STUDY DESIGN: A retrospective chart review was carried out to extract relevant clinical, histologic, and outcome data. Tissue blocks of resected specimens were re-examined for specific inflammatory response. RESULTS: Complete data and long-term follow up were available in 16 patients who underwent surgical intervention. All were cared for by the same practitioner (CM). The mean (+/- S.D.) age and gravidity on presentation were 26.9 +/- 5.3 years and 0.9 +/- 1.5, respectively. All but one was caucasian, and 70% were nulliparous. Symptoms included entry dyspareunia (100%), discharge (70%), burning (66%), itching (20%) and other (30%). All patients had focal tenderness; other findings were erythema (50%), acetowhite staining (80%), edema (20%), micropapules (20%) and condyloma (10%). After diagnosis, initial duration of conservative management was 9.4 +/- 6.9 months (1-26 months). No patients received interferon therapy. Because of persistent symptoms the 16 subjects underwent targeted partial perineoplasties. Initial histopathology results revealed chronic inflammation, parakeratosis, hyperkeratosis, edema, koilocytosis and acanthosis. When tissue blocks were cut and stained with Giemsa, large numbers of mast cells were identified. Mean postoperative follow up was 42.0 +/- 22.4 months (10-70 months). Follow up after surgery showed an overall improvement in 15/16 patients (93.8%). CONCLUSIONS: VV affects primarily white, nulliparous women. In the carefully selected subject, surgical intervention has a high success rate, even on long-term follow up. Although the exact etiology for this condition has yet to be elucidated, the presence of mast cells supports an association with other genitourinary inflammatory syndromes such as interstitial cystitis; and allows for speculation about a possible role played by mast cell activation in the etiology of VV.

Adult↗

Induction and posttranslational expression of cytokines in a first-trimester trophoblast cell line by lipopolysaccharide.

OBJECTIVES: The response to infection by human first-trimester trophoblasts is a poorly understood event. This study was undertaken to determine whether first-trimester trophoblasts are capable of responding to an infection stimulus and mediating an immune response. STUDY DESIGN: HTR-8/SVneo cells were exposed to lipopolysaccharide (1 microgram/ml) or media alone for either 0, 2, 4, 6, 8, or 24 hours. Northern analysis was conducted by use of a panel of antisense cytokine probes. Enzyme-linked immunosorbent assays specific for either interleukin-1 alpha, interleukin-6, interleukin-8, or transforming growth factor-beta 1 were conducted on corresponding cell culture supernatants, and the kinetics of expression were determined. RESULTS: Interleukin-1 alpha, interleukin-6, interleukin-8, and transforming growth factor-beta 1 transcription occurred maximally between 2 and 8 hours of culture in media containing lipopolysaccharide, with a subsequent diminution of response. Enzyme-linked immunosorbent assay analysis corroborated lipopolysaccharide induction seen at the level of transcription, with significant posttranslational expression of these cytokines being detected between 2 and 24 hours in culture (p < 0.01). CONCLUSIONS: Expression of the proinflammatory cytokines interleukin-1 alpha, interleukin-6, interleukin-8 and transforming growth factor-beta 1 strongly support the contention that human first-trimester trophoblasts are capable of responding to an infection stimulus and eliciting an immune response through cytokine-based immune signaling.

Blotting, Northern↗

Induction of inflammatory cytokines in placental monocytes of gravidae infected with the human immunodeficiency virus type 1.

Placental mononuclear cells (PMC) are susceptible to infection with the human immunodeficiency virus (HIV). PMC secreted tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta), and IL-6 among other factors, which, in turn, regulate HIV replication in latently infected cells. We assessed the induction of these cytokines in PMC from HIV-infected (HIV+) and uninfected (control) gravidae following exposure to lipopolysaccharide (LPS), HIV lysate (iHIV), recombinant HIV env (GP160) and HIV gag (gag55), and synthetic HIV p17 (HGP30) antigens. In comparison to control PMC, HIV+ PMC constitutively secreted higher levels of IL-1beta and IL-6 and were refractory to stimulation by iHIV, GP160, gag55, and HGP30. Control PMC IL-1 beta levels were boosted by LPS; gag55 and HGP30 augmented IL-6 but not IL-1 beta. Both groups exhibited low basal TNF-alpha production that was augmented by LPS. HIV+ PMC exhibited higher constitutive levels of IL-1 beta, IL-6, and TNF-alpha gene transcription than control PMC. These levels could be further augmented by LPS, yet the incremental levels were lower than those obtained from PMC of uninfected women. The high basal constitutive secretion of cytokines by HIV+ PMC and their refractoriness to activation may reflect a virus-mediated dysregulation of cytokine expression culminating in compromised host defenses against secondary opportunistic infections associated with AIDS.

Acquired Immunodeficiency Syndrome↗

Human trophoblast cell adhesion to extracellular matrix protein, entactin.

PROBLEM: Trophoblast interaction with endometrial extracellular matrix (ECM) is crucial during human embryo implantation and placentation. Entactin, a ubiquitous basement membrane glycoprotein, plays a central role in ECM assembly, cell attachment, and chemotaxis. The present study was conducted to examine the possible role of entactin in promoting human trophoblast adhesion. METHODS: Using an extended life span first trimester trophoblast cell line HTR-8/SVneo (HTR) and a cell adhesion assay, we measured the adherence of human first trimester trophoblasts to recombinant entactin and its domains. Also, we used flow cytometry and indirect immunofluorescence to detect the presence of integrins that may be involved in human trophoblast-entactin interaction; these methods were used to analyze HTR cells, as well as tissue sections and freshly isolated human trophoblasts from first trimester and term placenta. RESULTS: We found that first trimester trophoblast cells were highly adherent to entactin and its E and G2 domains but not to G1 or G3 domains. Using indirect immunofluorescence and flow cytometry, we found that both beta 1 and beta 3 integrin subunits were expressed on the surface of HTR trophoblast cells adhering to entactin; in contrast, beta 2 and beta 4 integrin subunits were not detected. In addition, we found that alpha v beta 3 was expressed on freshly isolated villous cytotrophoblasts and cytotrophoblast and syncytiotrophoblasts in tissue sections from term placenta. The beta 3 integrin subunit was expressed in cytotrophoblasts and syncytiotrophoblasts in villi of first trimester placental tissue sections. CONCLUSION: Recombinant entactin promotes human trophoblast cell adhesion through both its E and G2 domains and these specific adhesive interactions may be mediated by beta 1 and/or beta 3 class integrins.

Antigens, CD↗

Induction and postranslational expression of G-CSF and RANTES in a first trimester trophoblast cell line by lipopolysaccharide.

PROBLEM: Comparatively little is known about the capacity of first trimester trophoblasts to respond to an infection and coordinate an immune response. This study characterizes the LPS induction of G-CSF and RANTES in a first trimester trophoblast cell line. METHODS: HTR-8/SV neo cells were exposed to LPS (1 micrograms/ml) for 0, 2, 4, 6, 8, and 24 hours in DMEM-Ham's F-12 media supplemented with 10% fetal bovine serum. Cytokine levels in culture supernatants were measured by ELISA. Northern analysis of total RNA was conducted using antisense cytokine probes. RESULTS: Levels of immunoreactive G-CSF and RANTES from LPS induced cultures at 24 hours were 10-fold and 8.5-fold greater than cytokine levels from non-induced cells at 24 hours, respectively (P < 0.01). Under LPS induction, maximal rates of G-CSF and RANTES transcription occurred at 24 hours and 8 hours, respectively. CONCLUSION: The LPS induction of proinflammatory cytokines in a first trimester trophoblast cell line supports the contention that first trimester trophoblasts participate in cytokine based immune signaling in response to infection.

Blotting, Northern↗

The interaction between cytotrophoblasts and their derived tumor cells.

Previous experiments demonstrated that human cytotrophoblasts and cells of the choriocarcinoma cell line JAr interact in vitro. As a result of this interaction there is an increased synthesis of CG and hPL, probably as a result of the increased CG and hPL synthesis by the cytotrophoblasts. In the present investigation we studied this interaction in greater detail and found that both cytotrophoblasts and JAr cells undergo changes in their biological properties as a result of this interaction. JAr cells and cytotrophoblasts cocultured for 72 hr were fractionated according to their size by centrifugal elutriation. The number of cells in the fraction which contain the largest cells was very significantly increased as a result of the coculture. This increase was due to an increase in the number of cells of both cell types. This fraction was the most active one in the synthesis of CG and hPL. The synthesis of DNA by the JAr nuclei in this fraction of the cocultured cells was almost completely inhibited but in the parallel fraction of the JAr cells cultivated alone the level of DNA synthesis was equal to that of all other JAr cell fractions. Heterokaryons are formed in the coculture. In these heterokaryons a factor which inhibits DNA synthesis in the cytotrophoblasts may inhibit DNA synthesis in JAr nuclei and at least be partly responsible for the inhibition of DNA synthesis observed.

Animals↗

Pulmonary hypoplasia: pathogenesis, diagnosis, and antenatal prediction.

OBJECTIVE: To review published data pertaining to the pathogenesis, antenatal prediction, and neonatal diagnosis of pulmonary hypoplasia. DATA SOURCES: A computerized search of articles published through February 1995 was performed on the MEDLINE data base. Additional sources were identified through cross-referencing. METHODS OF STUDY SELECTION: All available references were reviewed initially by the authors, and their impact on the clinical significance of this condition was summarized. DATA EXTRACTION AND SYNTHESIS: Pulmonary hypoplasia can be understood best by first defining the embryology of lung development. Although pulmonary hypoplasia can occur as a primary event, most cases are secondary to congenital anomalies or pregnancy complications. Several methods have been proposed to predict the subsequent occurrence of pulmonary hypoplasia, but no single criterion has adequately confirmed sensitivity and specificity for clinical decision making. CONCLUSION: For patients with premature rupture of membranes, the gestational age at time of rupture carries the highest risk correlation with subsequent pulmonary hypoplasia.

Congenital Abnormalities↗

Down's syndrome as a model for the decisive role of maternal lineage in human evolution.

The study of human evolution and the mechanism of this process can be approached from physical anthropology, which examines phenotypic expression and molecular evolution, which investigates genotypic change. Alternatively, we suggest that human evolutional process can also be explained using present day examples of abberations in evolution. Thus, from both genotypic and phenotypic perspectives, we address the question of whether Down's syndrome is an instructive example to look into the decisive role of maternal lineage in human evolution.

Animals↗

Relaxation of imprinting in trophoblastic disease.

Genomic imprinting--the uniparental-dependent transmittance of a genetic trait--has been accepted in recent years as a major mechanism in mammalian genetics. We studied the expression of the H19 gene, a parentally imprinted (maternally expressed) gene, by in situ hybridization in human placenta and trophoblastic disease. Expression was found to be abundant, in a decreasing order, in the intermediate trophoblast (villous and interstitial), the cytotrophoblast, and the syncytiotrophoblast. The villous stroma was also prominently labeled. Partial hydatidiform mole showed a similar pattern of expression as normal placenta. As expected, complete hydatidiform mole, whose genome consists of two haploid sets of paternal origin, was not labeled in the villous stroma and surrounding trophoblastic layer. However, some of the large mononuclear cells in the proliferating groups sprouting from the villous surface were strongly labeled. Prominent expression of H19 was found in placental site trophoblastic tumor and gestational choriocarcinoma. The phenomenon of emergence of expression of alleles subject to repression according to their gamete of origin is termed relaxation of imprinting, and is considered to be relevant to tumorigenesis. We suggest that the expression of the maternally expressed H19 gene in the androgenetic tissue of complete hydatidiform mole represents relaxation of imprinting and may be associated with its malignant potential.

Choriocarcinoma↗

A growing relationship between genomic imprinting and tumorigenesis.

The association between aberrations of the human genome and the development of cancer is well established. Gene imprinting, defined as gene expression based on the gamete of origin, has previously been shown to be involved in this process by the loss of tumor suppressor gene regulation. We suggest that the activation of imprinted proto-oncogenes and growth factors may also play a vital role in tumorigenesis. Mechanistically, this can occur when the gene is removed from its imprinted sequence area, thus escaping repression. Synteny between the human and mouse genome provides the opportunity for targeted studies of imprinted genes suspected to be involved in cancer.

Animals↗

The role of genomic imprinting in implantation.

OBJECTIVES: To outline the possible role of the imprinted genes in early human embryogenesis and implantation. DATA IDENTIFICATION: Literature review. STUDY SELECTION: Studies examining the issues of genomic imprinting, implantation, gestational trophoblastic diseases, placental gene expression, and trophoblast invasion. RESULTS: Certain genes have been shown to be expressed either in the embryo or in the uterine decidua before implantation. Some of these have been shown to be parentally imprinted, that is, expressed either from their paternal or maternal origin. The paternally expressed genes are linked to placental proliferation and invasiveness. CONCLUSIONS: Clinical and basic data from different disciplines indicate that genomic imprinting may be crucial to the process of implantation.

Animals↗

Herpes simplex virus.

Herpes simplex virus (HSV) infection in the obstetric and gynecologic patient remains an actively researched area. Recent studies better clarifying issues pertaining to viral transmission, diagnosis, management, and treatment are presented. These investigations emphasize the importance of understanding the molecular biology of this organism when developing diagnostic and treatment modalities. Natural history studies continue to reveal significant aspects of viral behavior and its impact on the human host.

Female↗

Ultrastructural characteristics of cytotrophoblast cells during stages of differentiation.

Isolated cytotrophoblast cells from term human placenta were separated into eleven fractions according to cell size, by centrifugal elutriation. Each fraction isolated was examined by electron microscopy to elucidate ultrastructural features consistent with differences in stages of cellular differentiation. As a rule, increasing cell size correlated with evidence of progressive intracellular differentiation. This was represented by the appearance of specialization structures in later fractions, and by changes in the density of organelles and other cellular constituents. Progressive development and maturation of the rough endoplasmic reticulum was also evident. These data are the first to demonstrate successful subfractionation of the heterogeneous cytotrophoblast cell population into distinct groups, each representing different levels of cellular differentiation. These morphologic features of differentiation correlate closely with established biochemical parameters associated with various stages of intermediate cytotrophoblast cell differentiation.

Cell Differentiation↗

Use of a novel system for defining a gene imprinting region.

Gene imprinting involves the expression of a single allele, depending on its parental origin. In this report, we describe the use of a novel system, implementing human tissues exclusively endowed with either maternally or paternally inherited chromosomes, to better define a known gene imprinting region. Specific RNA transcripts for Placental Ribonuclease Inhibitor (PRI) and Cathepsin D were analysed by northern blotting for expression in complete hydatidiform mole, mature teratoma, and normal placenta. These genes are in close proximity to the reciprocally imprinted H19 and IGF-2 genes found on chromosome 11p15.5. Since all the tissues studied expressed Cathepsin D and PRI, these are not, by definition, imprinted, but as yet we cannot define the borders of the imprinting area on chromosome 11p15.5.

Alleles↗