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Biomedical subjects

G Olson

Publications and source records attributed to G Olson.

At least 19 recordsLinked to original sources

Non-invasive transabdominal uterine electromyography correlates with the strength of intrauterine pressure and is predictive of labor and delivery.

OBJECTIVE: The study was conducted to investigate whether the strength of uterine contractions monitored invasively by intrauterine pressure catheter could be determined from transabdominal electromyography (EMG) and to estimate whether EMG is a better predictor of true labor compared to tocodynamometry (TOCO). STUDY DESIGN: Uterine EMG was recorded from the abdominal surface in laboring patients simultaneously monitored with an intrauterine pressure catheter (n = 13) or TOCO (n = 24). Three to five contractions per patient and corresponding electrical bursts were randomly selected and analyzed (integral of intrauterine pressure; integral, frequency, amplitude of contraction curve on TOCO; burst energy for EMG). The Mann-Whitney test, Spearman correlation and receiver operator characteristics (ROC) analysis were used as appropriate (significance was assumed at a value of p < 0.05). RESULTS: EMG correlated strongly with intrauterine pressure (r = 0.764; p = 0.002). EMG burst energy levels were significantly higher in patients who delivered within 48 h compared to those who delivered later (median [25%/75%]: 96,640 [26,520-322,240] vs. 2960 [1560-10,240]; p < 0.001), whereas none of the TOCO parameters were different. In addition, burst energy levels were highly predictive of delivery within 48 h (AUC = 0.9531; p < 0.0001). CONCLUSION: EMG measurements correlated strongly with the strength of contractions and therefore may be a valuable alternative to invasive measurement of intrauterine pressure. Unlike TOCO, transabdominal uterine EMG can be used reliably to predict labor and delivery.

Abdomen↗

Amniotic fluid index measured with the aid of color flow Doppler.

OBJECTIVE: To determine whether using color flow Doppler to identify the umbilical cord affects amniotic fluid index (AFI) measurements. METHODS: A total of 2236 AFI measurements between 24 and 42 weeks in singleton gestations with no known or suspected fetal anomalies and < 14 days' discrepancy between menstrual and ultrasonographic dating were included. Color flow Doppler was used to identify loops of umbilical cord; these were excluded from the measurement. Polynomial regression was used to generate means and centiles. Data were grouped according to completed weeks of gestation and descriptive statistics were calculated. At each week of gestation, the number and percentage of pregnancies diagnosed as < or = 2.5th, < or = 5th, > or = 95th, and > or = 97.5th centile according to a 'standard' nomogram derived without using color flow Doppler were calculated. RESULTS: The AFI decreased significantly over gestational age, starting at 31 weeks (p < 0.05 by ANOVA). The relationship between AFI and gestational age was best modeled by a second-degree polynomial (p < 0.001). The median and range of the proportion of AFIs that fell outside the ranges of the standard nomogram at each completed gestational age was: 6.0 (2.3-35.4)% for the < or = 2.5th centile, 9.9 (3.1-37.5)% for the < or = 5th centile, 3.8 (0-30)% for the > or = 95th centile, and 1.8 (0-20)% for the > or = 97.5th centile. The 2.5th and 5th centiles using the current data were lower than those of the 'standard', and the difference increased with advancing gestation. Upper centiles were also different. CONCLUSION: The AFI measured using color flow Doppler overestimates oligohydramnios and may underestimate polyhydramnios when a standard AFI table obtained without color flow Doppler is used. Normal values specific for measurement method should be used for reference.

Amniotic Fluid↗

The use of lymphoscintigraphy and PET in the management of head and neck melanoma.

OBJECTIVES: Lymphoscintigraphy with sentinel node dissection and 18 fluoro-2-deoxyglucose positron emission tomography (PET) are being used independently in the management of many intermediate and thick melanomas of the head and neck. We report a series of patients with melanoma of the head and neck with Breslow depths greater than 1.0 mm and clinically negative regional nodes that were evaluated prospectively with PET and lymphoscintigraphy. STUDY DESIGN AND SETTING: Between July 1, 1998 and December 30, 2000 PET scans were obtained preoperatively on 18 patients undergoing resection of head and neck melanoma. Lymphoscintigraphy and sentinel node dissection was performed. Resection of the primary lesion was then carried out with adequate margins and the defects were reconstructed. RESULTS: Sentinel node(s) were found in 17/18 patients (94.4%); 5/18 (27.8%) of cases had metastases. PET detected nodal metastasis preoperatively in 3 patients (16.7%), one of which had a positive sentinel node dissection. CONCLUSION: PET and lymphoscintigraphy offer complimentary ways of evaluation for metastatic melanoma.

Aged↗

Androgen receptors in thymic epithelium modulate thymus size and thymocyte development.

Castration of normal male rodents results in significant enlargement of the thymus, and androgen replacement reverses these changes. Androgen-resistant testicular feminization (Tfm) mice also show significant thymus enlargement, which suggests that these changes are mediated by the androgen receptor (AR). The cellular targets of androgen action in the thymus are not known, but may include the lymphoid cells (thymocytes) as well as nonlymphoid epithelial cells, both of which have been believed to express AR. In the present study immunohistochemical analysis and hormone binding assays were used to demonstrate the presence of AR in thymic epithelial cells. The physiological significance of this epithelial cell AR expression was defined by further studies performed in vivo using chimeric mice, produced by bone marrow transplantation, in which AR expression was limited to either lymphoid or epithelial components of the thymus. Chimeric C57 mice engrafted with Tfm bone marrow cells (AR(+) epithelium and AR(-) thymocytes) had thymuses of normal size and showed the normal involutional response to androgens, whereas chimeric Tfm mice engrafted with C57 bone marrow cells (AR(-) epithelium and AR(+) thymocytes) showed thymus enlargement and androgen insensitivity. Furthermore, phenotypic analyses of lymphocytes in mice with AR(-) thymic epithelium showed abrogation of the normal responses to androgens. These data suggest that AR expressed by thymic epithelium are important modulators of thymocyte development.

Animals↗

Pregnancy and primary pulmonary hypertension : successful outcome with epoprostenol therapy.

Primary pulmonary hypertension (PPH) associated with pregnancy carries a high maternal mortality rate. Short-term epoprostenol infusion has been demonstrated to improve the hemodynamic profile in patients with PPH. We report a successful maternal-fetal outcome with epoprostenol therapy during pregnancy, cesarean section, and postpartum in a patient with PPH. Epoprostenol therapy did not produce any physical or developmental abnormalities in the fetus. A favorable maternal-fetal outcome may occur with a multidisciplinary approach.

Adult↗

Changes in light-induced fluorescence of cervical collagen in guinea pigs during gestation and after sodium nitroprusside treatment.

Light-induced fluorescence (LIF) of collagen was used to investigate in vivo changes in cervical collagen in guinea pigs during gestation and following sodium nitroprusside treatment. Natural fluorescence of collagen is due to collagen cross-linking molecules that connect single collagen fibers and therefore provide rigidity of the cervical stroma. LIF of cervical collagen was measured from the surface of the exocervix in anesthetized nonpregnant and timed pregnant guinea pigs at different times of gestation with an instrument designed in our lab (Collascope). Measurements were also performed in guinea pigs at midgestation before and 8 hours after intracervical treatment with sodium nitroprusside. Collagen fluorescence decreased significantly as pregnancy progressed, reached lowest values at delivery, and increased gradually postpartum. Treatment with sodium nitroprusside, but not with the vehicle, caused a significant decrease in LIF (p = 0.007). We conclude, that LIF changes in the cervix reflect the gradual cervical softening (ripening) during pregnancy and the return to the rigid state of the cervix postpartum. Cervical softening during pregnancy, and after sodium nitroprusside treatment, is associated with a decrease in collagen cross-links. Measurements of LIF can be used to investigate cervical softening in vivo.

Animals↗

Drug discovery.

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Drug Design↗

A role for poly(ADP-ribose) polymerase in the transcriptional regulation of the melanoma growth stimulatory activity (CXCL1) gene expression.

The melanoma growth stimulatory activity/growth-regulated protein, CXCL1, is constitutively expressed at high levels during inflammation and progression of melanocytes into malignant melanoma. It has been shown previously that CXCL1 overexpression in melanoma cells is due to increased transcription as well as stability of the CXCL1 message. The transcription of CXCL1 is regulated through several cis-acting elements including Sp1, NF-kappaB, HMGI(Y), and the immediate upstream region (IUR) element (nucleotides -94 to -78), which lies immediately upstream to the nuclear factor kappaB (NF-kappaB) element. Previously, it has been shown that the IUR is necessary for basal and cytokine-induced transcription of the CXCL1 gene. UV cross-linking and Southwestern blot analyses indicate that the IUR oligonucleotide probe selectively binds a 115-kDa protein. In this study, the IUR element has been further characterized. We show here that proximity of the IUR element to the adjacent NF-kappaB element is critical to its function as a positive regulatory element. Using binding site oligonucleotide affinity chromatography, we have selectively purified the 115-kDa IUR-F. Mass spectrometry/mass spectrometry/matrix-assisted laser desorption ionization/time of flight spectroscopy and amino acid analysis as well as microcapillary reverse phase chromatography electrospray ionization tandem mass spectrometry identified this protein as the 114-kDa poly(ADP-ribose) polymerase (PARP1). Furthermore, 3-aminobenzamide, an inhibitor of PARP-specific ADP-ribosylation, inhibits CXCL1 promoter activity and reduces levels of CXCL1 mRNA. The data point to the possibility that PARP may be a coactivator of CXCL1 transcription.

Adenosine Diphosphate Ribose↗

Reinforced variability and operant learning.

Reinforcement of variability may help to explain operant learning. Three groups of rats were reinforced, in different phases, whenever the following target sequences of left (L) and right (R) lever presses occurred: LR, RLL, LLR, RRLR, RLLRL, and in Experiment 2, LLRRL. One group (variability [VAR]) was concurrently reinforced once per minute for sequence variations, a second group also once per minute but independently of variations, that is, for any sequences (ANY), and a control group (CON) received no additional reinforcers. The 3 groups learned the easiest targets equally. For the most difficult targets, CON animals' responding extinguished whereas both VAR and ANY responded at high rates. Only the VAR animals learned, however. Thus, concurrent reinforcers--contingent on variability or not--helped to maintain responding when difficult sequences were reinforced, but learning those sequences depended on reinforcement of variations.

Animals↗

Image-guided functional endoscopic sinus surgery.

INTRODUCTION: Computer-aided surgery (CAS) technology in functional endoscopic sinus surgery (FESS) has engendered considerable discussion. OBJECTIVE: The goals of this study were to describe CAS preoperative planning (software-based CT image analysis) and to develop intraoperative CAS strategies for endoscopic sinus surgery. STUDY DESIGN: Between October 1, 1997, and December 31, 1998, the StealthStation (Sofamor Danek, Memphis, TN) was used in 61 FESS cases, and a retrospective review of the findings was performed. The indication for surgery in all instances was chronic rhinosinusitis refractory to medical management. The StealthStation was used to review all CT scans before surgery. Anatomic fiducial registration supplemented by contour mapping was used. RESULTS: Localization accuracy was estimated to be within 2 mm or better. The StealthStation was used for both CT image review and intraoperative localization. CAS was useful in the frontal recess, sphenoethmoid region, posterior ethmoid system, and skull base area. CAS was deemed helpful in situations where the surgical anatomy was altered by previous surgery and extensive inflammatory disease (polyposis, fungal sinusitis, and pansinusitis). CONCLUSION: The paradigm of image-guided FESS surgery, which integrates CAS into FESS, will serve to increase surgical effectiveness and decrease surgical morbidity.

Adult↗

The effect of fetal neck position on nuchal fold thickness.

OBJECTIVE: Our purpose was to determine whether ultrasonographic measurements of nuchal fold thickness are affected by the position of the fetal neck. STUDY DESIGN: Fetal nuchal fold thickness was prospectively measured in 258 women undergoing routine ultrasonography at 15 to 21 completed weeks of gestation. Patients with fetal structural or chromosomal anomalies were excluded. At the time of examination the position of the fetal head was noted as being extended or flexed on the basis of the angle between the spine and the base of the skull. Gestational age was based on menstrual dates or ultrasonographic biometric parameters. Data were tested for normality. Mann-Whitney U test and analysis of covariance were used (significance was considered to be P <.05). Data are presented as median and range. RESULTS: A total of 258 fetuses were examined with 167 (65%) in the flexed and 91 (35%) in the extended neck position. Gestational age was not significantly different between the flexed and extended groups (median, 19.1 weeks; range, 15.5-21.6 weeks; vs median, 19.1 weeks; range, 15.6-22 weeks; P =.23). Nuchal fold thickness was significantly lower in the flexed group than in the extended group (median, 3.5 mm; range, 1.3-6.2 mm; vs median, 3.9 mm; range, 2.2-4.9 mm; P =.0097). Nuchal fold thickness increased significantly with gestational age in both groups. The difference in nuchal fold thickness between the 2 groups persisted even after the increase in nuchal fold thickness was adjusted for with gestational age (P =.002, analysis of covariance). The difference between the 2 groups was higher at earlier gestations. CONCLUSION: Nuchal fold thickness is affected by gestational age and fetal neck position. Correction for these variables may improve the accuracy of nuchal fold thickness measurements in screening for fetal chromosomal anomalies.

Female↗

Expression of the human antigen SPAG2 in the testis and localization to the outer dense fibers in spermatozoa.

ABSTRACT Antisperm antibodies (ASAs) have been implicated in some instances of infertility. To characterize sperm antigens relevant to immunologic and immunocontraceptive development, SPAG2 (sperm-associated antigen 2) was identified by screening a human testis cDNA library with human sera positive for ASAs. Subsequently, two isoforms, SPAG2-1 and SPAG2-2, were identified in testis and placenta libraries, respectively. In the current study, Southern analysis of human genomic DNA with a probe common to the two SPAG2 isoforms indicated a single SPAG2 gene; therefore, alternative splicing is a likely mechanism for production of variant mRNAs. In situ hybridization of human testis sections demonstrated the expression of SPAG2 in primary spermatocytes, with decreased or arrested expression in postmeiotic cells. Immunofluorescence of Triton X-100-extracted spermatozoa with an anti-SPAG2 peptide antiserum indicate that SPAG2 is an intracellular component of the sperm flagellum. Electron microscopy refined this localization to the outer dense fibers (ODFs), structural filaments associated with the mammalian sperm axoneme. The ODFs have been reported to be composed of keratin-like intermediate filament proteins. However, SPAG2 does not exhibit the molecular characteristics of such proteins, nor does SPAG2 demonstrate sequence homology with previously characterized ODF proteins. Therefore, SPAG2 represents a novel protein of human sperm ODFs. Characterization of SPAG2 will further our understanding of ODF function in normal sperm motility and of flagellar abnormalities that lead to male infertility.

Antigens, Surface↗

Instrumentation for the diagnosis of term and preterm labour.

The problems associated with labor during pregnancy are among the most important health issues facing physicians. Understanding the role of the uterus and cervix in labor and developing methods to control their function is essential to solving problems relating to labor. At the moment, only crude, inaccurate and subjective methods are used to assess changes in the uterus and cervix that occur in preparation for or during labor. In the past several years, we have developed noninvasive methods to quantitatively evaluate the uterus and cervix based respectively on recording of uterine electrical signals from the abdominal surface (uterine EMG) and measurement of light-induced cervical collagen fluorescence (LIF) with an optical device (Collascope). The methods are rapid and allow assessment of uterine contractility and cervical ripening. Studies in rats and humans indicate that uterine and cervical function can be successfully monitored during pregnancy using these approaches and that these techniques might be used in a variety of conditions associated with labor to better define management. The potential benefits of the proposed instrumentation and methods include a reducing the rate of preterm delivery, improving maternal and perinatal outcome, monitoring treatment, decreasing cesarean section rate and improving research methods to understand uterine and cervical function.

Animals↗

Prevention by retinoids of azoxymethane-induced tumors and aberrant crypt foci and their modulation of cell proliferation in the colon of rats.

Retinoids are proposed chemopreventive agents that inhibit cell proliferation and induce differentiation. Their ability to prevent azoxymethane (AOM)-induced aberrant crypt foci (ACF) and tumors and to modulate cell proliferation was investigated in the colon of male F344 rats. Thirteen retinoids were evaluated for prevention of ACF and two of them, 9-cis-retinoic acid (RA) and 4-(hydroxyphenyl)retinamide (4-HPR), were also evaluated for prevention of colon cancer. The retinoids were administered continuously in the diet starting 1 week prior to the first of two weekly 15 mg/kg i.p. injections of AOM and for a total of either 5 or 36 weeks in order to evaluate their effect on colonic ACF and tumors. At a concentration of 1 mmol/kg diet, 2-(carboxyphenyl)retinamide caused the greatest reduction (57.7%) in the yield of ACF. 9-cis-RA was toxic at 1 mmol/kg so that it was evaluated at 0.1 mmol/kg, resulting in a 41.6% reduction in ACF. The ability of the retinoids to reduce the proliferating cell nuclear antigen (PCNA) labeling index in ACF and in non-involved crypts correlated with their ability to prevent ACF. Both 9-cis-RA (0.1 and 0.2 mmol/kg diet) and 4-HPR (1 and 2 mmol/kg diet) were highly effective in decreasing the yield of AOM-induced colon tumors. In summary, retinoids were demonstrated to reduce cell proliferation and to prevent ACF and tumors in the colon, suggesting promise as preventive agents for colon cancer.

Alitretinoin↗

Mediation of inflammation by cyclooxygenase-2.

Non-steroidal antiinflammatory drugs (NSAIDs) are commonly used for the treatment of inflammation, pain, and fever. Mechanistically, these compounds are believed to act via inhibition of the enzyme cyclooxygenase (COX), which catalyzes the conversion of arachidonic acid to the prostaglandins (PGs). Although commercially available NSAIDS are efficacious antiinflammatory agents, significant side effects limit their use. Recently two forms of COX were identified- a constitutively expressed COX-1 and a cytokine-inducible COX-2. Commercially available NSAIDs like indomethacin inhibit both COX-1 and COX-2 suggesting the hypothesis that toxicities associated with NSAID therapy are due to inhibition of the non-regulated or constitutive form of COX (COX-1) in normal tissues, whereas therapeutic benefit derives from inhibition of the inducible enzyme, COX-2, at the site of inflammation. Therefore, a selective inhibitor of COX-2 may be anti-inflammatory without GI toxicity-providing a significant improvement over currently available NSAIDs.

Animals↗

Acute alterations in the regulation of lipid metabolism after intravascular reexposure to a single bolus of homologous virus during influenza B infection in ferrets: possible model of epiphenomena associated with influenza.

Metabolic responses occurring 24 h following the secondary haematogenous dissemination of influenza B virus during convalescence from infection were examined in the ferret as a possible model for epiphenomena which can occur following infection with influenza. Among the major changes found were a further rise in the mean fasting serum free fatty acid (FFA) level to three times the control mean value and a 50% drop in the mean serum triglyceride (TG) concentration after the intravascular administration of a single bolus of virus compared to levels found in uninfected or convalescent animals. In adipose tissue, hormone-sensitive and lipoprotein lipase activities were increased six and three-fold, respectively, over mean control values, probably accounting for the changes that were observed in serum lipid concentrations. In the liver, total carnitine palmitoyltransferase (CPT) activity was affected only slightly and the total lipid content of the liver remained unchanged. These findings indicate that 24 h after the intravascular dissemination of homologous virus in a single bolus during convalescence from influenza B infection, major distortions in the regulation of lipid metabolism occur in the ferret. Loss of the synchronous regulation of the two adipose tissue lipases is a significant consequence leading to the mobilization of a large amount of FFA during fasting from both adipose tissue and the circulating plasma TG stores.

Adipose Tissue↗