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Biomedical subjects

S Segal

Publications and source records attributed to S Segal.

At least 109 records · Page 6Linked to original sources
PubMed1998

Placental tissue enhances uterine relaxation by nitroglycerin.

UNLABELLED: Nitroglycerin (TNG) has recently gained popularity in obstetric anesthesia for facilitating acute uterine relaxation in the treatment of obstetric emergencies such as retained placenta. Laboratory investigations, however, have consistently found the uterus insensitive to clinically used doses of TNG. We hypothesized that the presence of the placenta in the uterus may be important for TNG to be effective, because it has been present in most clinical reports and has generally been absent in laboratory investigations. Sections of near-term gravid rat uteri were mounted for isometric force recording. We studied spontaneous contractions and acetylcholine-induced sustained contractions both with and without the addition of minced placental tissue in close approximation to the uterine muscle. Phenylephrine-precontracted rings of thoracic aorta were studied as a positive control. Log dose-response curves for TNG, 10(-9) to 10(-5) M, were constructed for each tissue. Uterine muscle alone was resistant to all but the largest doses of TNG, both in spontaneous and sustained contraction models. The addition of placental tissue caused a marked increase in sensitivity, reducing spontaneous uterine contractions by 50% at log -5.92 M (95% confidence interval, -6.49, -5.05), which was comparable to the sensitivity in aorta. Nitric oxide (NO) inhibitors pyrogallol (a superoxide anion generator) and methylene blue (a guanylate cyclase inhibitor) completely blocked the effect of TNG in the presence of placenta. Placental tissue modestly increased the response of aorta to TNG, but not of uterine tissue to the NO-independent uterine relaxants MgSO4 and terbutaline. IMPLICATIONS: Nitroglycerin can relax the human uterus during obstetric emergencies, but the drug has never been proven effective in the laboratory. This study shows that nitroglycerin can relax uterine contractions in the rat, provided that the placenta is adjacent to the uterus. The mechanism seems to be via the release of nitric oxide.

Acetylcholine↗
PubMed1998

The tocolytic effect of catecholamines in the gravid rat uterus.

UNLABELLED: Maternal catecholamines increase dramatically in labor because of pain and emotional stress. Because the uterus is richly endowed with both alpha- and beta-adrenergic receptors, catecholamines could alter uterine activity. We assessed the effect of clinically encountered concentrations of these catecholamines on uterine activity and modeled the effect of the abrupt reduction in circulating epinephrine that occurs during effective labor analgesia. Term pregnant rat uteri were excised, and cross-sectional rings were mounted for isometric force recording. Log concentration-response curves for epinephrine, norepinephrine, and their combination on uterine activity were constructed from 10(-12) to 10(-6) M. Catecholamine responses were repeated in the presence of phentolamine, an alpha-adrenergic blocker or propranolol, a beta-adrenergic blocker. The abilities of oxytocin and of washout of catecholamines to reverse catecholamine-induced changes in uterine activity were also assessed. Epinephrine caused dose-dependent reductions in uterine activity, blocked by propranolol. Epinephrine concentrations in the clinical range(10(-9) to 10(-8) M; 100-1000 pg/mL) decreased uterine activity to 49.6% +/- 6.6% (mean +/- SE) of control. Norepinephrine caused a dose-dependent increase in uterine activity, which was blocked by phentolamine. In the clinical range (10(-8) M), uterine activity was 139.2% +/- 13.40% of control. The combination of both catecholamines, however, was nearly as tocolytic as epinephrine alone. Oxytocin antagonized catecholamine-induced tocolysis, and washout of epinephrine or both catecholamines increased uterine activity. We conclude that mixed catecholamines are significantly tocolytic at concentrations encountered in laboring women. In this in vitro model, reduction in epinephrine concentration, comparable to that which occurs during effective analgesia, significantly increases uterine activity. IMPLICATIONS: Maternal catecholamines increase in labor, but epinephrine decreases dramatically after regional analgesia. In this study, we found that norepinephrine and epinephrine together decrease uterine contractile activity and that decreased epinephrine causes significantly increased uterine activity.

Adrenergic alpha-Antagonists↗
PubMed1998

The role of protein kinase C in G1 and G2/M phases of the cell cycle (review).

The protein serine/threonine kinases--members of protein kinase C (PKC) family--are important components of the major signaling pathways regulating cell proliferation and differentiation. Recent studies implicate PKC in cell cycle control at two sites--during G1 to S progression and at G2 to M transition. Activation of PKC during G1 progression modulates the activity of the specific cyclin-dependent kinases (CDKs), which phosphorylate the retinoblastoma susceptibility gene product (RB). Phosphorylation of RB is a pivotal event in cell cycle progression leading to G1/S transition. PKC mediated enhancement or inhibition of CDK's activity and the RB phosphorylation state appear to be dependent on the precise timing of PKC activation during G1 and on the particular cell type. At G2/M transition, recent evidence suggests that PKC is involved in the regulation of CDC2 activity, although it is mostly implicated as a regulator of lamin B phosphorylation and the nuclear lamina disassembly.

Animals↗
PubMed1998

Thrombocytopenia with the HELLP syndrome. Report of two cases with reversal in normotensive and nonproteinuric gravidas.

BACKGROUND: In the absence of hypertension and proteinuria, pregnant women with hemolysis, elevated liver enzymes and low platelet count (HELLP syndrome) present a diagnostic and therapeutic problem. CASES: Two atypical cases occurred of HELLP syndrome diagnosed by hemolysis, elevated liver enzymes and low platelet count. The patients presented early in the third trimester with epigastric pain and lacked the usual signs of preeclampsia, such as hypertension and proteinuria. The patients were managed expectantly; during this time they became hypertensive, but the thrombocytopenia resolved. CONCLUSION: Pregnant women with hemolysis, elevated liver enzymes and thrombocytopenia who do not have hypertension or proteinuria should undergo complete diagnostic evaluation. If other etiologies are ruled out, the patient should be managed as appropriate for severe preeclampsia complicated by the HELLP syndrome.

Adult↗
PubMed1997

Epidermal growth factor regulates protein kinase A activity in murine fibrosarcoma cells: differences between metastatic and nonmetastatic tumor cell variants.

The interplay between cyclic AMP (cAMP)-dependent protein kinase A (PKA)- and p21ras-mediated signaling pathways is expected to determine further loss, maintenance, or modulation of differentiation and proliferation of a particular cell. Therefore, the relationship and nature of the cross-talk between these two major signaling systems are of utmost importance to the understanding of these processes in both normal and neoplastic cells. In view of their paramount physiological importance, one would expect the existence of a well-controlled bidirectional interaction between these pathways, which would be more appropriate and in agreement with basic principles of cellular homeostasis. However, based on the discovery that activated PKA may inhibit ras-mediated translocation of c-Raf-1 to the plasma membrane, it is generally accepted that the cross-talk between cAMP/PKA and p21ras-mediated signal transduction pathways is unilateral, i.e., that the activation of PKA regulates growth factor receptor protein tyrosine kinase-mediated signaling. To challenge the validity of a unilateral approach, we decided to test the possible existence of cross-talk of a bidirectional nature between the aforementioned signaling pathways at different stages of malignant differentiation. For that purpose, we investigated the nature of the cross-talk existing between a known receptor protein tyrosine kinase-epidermal growth factor receptor (EGFR) and PKA in highly metastatic and nonmetastatic cloned variants of a murine fibrosarcoma (T-10). Our study revealed the existence of principal differences in PKA activity between metastatic and nonmetastatic cloned fibrosarcoma variants that may be due to the differential expression and membrane translocation of the p21(Ki-ras) small mass G-protein. Most importantly, our experiments have demonstrated the existence of a novel character of interactions between EGFR and PKA, because the ligation of the EGFR by epidermal growth factor in the metastatic variant induced a high activity of PKA. These findings are of prime importance, because they reveal the existence of a new relationship between two major signal transduction pathways in mammalian cells, i.e., the existence of a bilateral interaction between the ras- and cAMP/PKA-mediated signal transduction pathways. Furthermore, the fact that two tumor cell variants originating in the same tumor and differing in their metastatic capacity differ as well in the nature of the cross-talk between major signal generation systems imposes new challenges for the future use of biological response modulators to cure cancer and restrict metastatic spread.

3T3 Cells↗
PubMed1997

Inhibition of tumorigenicity in lung adenocarcinoma cells by c-erbB-2 antisense expression.

The lung carcinoma cell line Calu3, which overexpresses the c-erbB-2 oncogene, was stably transfected with antisense (AS) cDNA constructs encompassing different regions of the c-erbB-2 gene. Transfected cells were analyzed for their tumorigenic properties in vitro and in nude mice. Two independent clones, AS F1 (low erbB-2 expressor) and AS B12 (high erbB-2 expressor), as well as the polyclonal Calu3/AS 5', were selected for these analyses. In Calu3/AS 5' transfected cells and in the AS F1 clone, c-erbB-2 RNA and protein levels were lower than those detected in the parental cell line and the AS B12 clone. Anchorage-independent growth and tumor take were also significantly reduced. Furthermore, cells derived from primary tumors of Calu3/AS 5', AS F1 and AS B12 lost the AS c-erbB-2 DNA insert but retained the gene for G418 resistance. Our results suggest that a correlation between c-erbB-2 overexpression and tumorigenicity may exist in the Calu3 lung carcinoma cell line.

Adenocarcinoma↗
PubMed1997

The effects of measles virus persistent infection on AP-1 transcription factor binding in neuroblastoma cells.

Measles virus (MV) persistence in brain cells has broad effects on different cellular functions. We have previously shown that NS20Y clone, originally derived from C1300 neuroblastoma cells, persistently infected with MV (NS20Y/MS), displays constitutively elevated levels of c-fos and PKC mRNAs, implying MV-mediated effects on transcriptional regulation. Nonetheless, the mode by which virus affects the transcriptional machinery still remains obscure. In order to define this phenomenon, we studied the binding properties of major transcription factors (AP-1 and NFkappaB) in NS20Y/MS cells. Using electrophoretic mobility shift approach (EMSA) with the appropriate oligonucleotide probes, we have found that the persistent MV infection does not affect NFkappaB binding, while the AP-1 binding was significantly decreased. Similar inhibition was not observed in NS20Y cells acutely infected with MV. Anti-measles antibody-mediated restriction of viral gene expression restored AP-1 binding, thus suggesting that measles virus proteins may affect the components of the host transcriptional machinery.

Animals↗
PubMed1997

Umbilical cord androgens in infants of diabetic mothers.

The aim was to measure umbilical cord testosterone and androstenedione and to explore possible relationships with fetal weight and insulin levels. Testosterone, androstenedione and insulin were measured at birth in venous umbilical blood in 12 infants of gestational diabetic mothers and in 12 control subjects. The mean concentrations of umbilical testosterone and androstenedione were not significantly different between the infants of the diabetic and control mothers. No significant correlation was found between maternal weight, fetal weight or insulin concentrations and androgen levels.

Androstenedione↗
PubMed1997

Labour pain management in a parturient with an implanted intrathecal pump.

PURPOSE: We report the peripartum anaesthetic management for vaginal delivery of a chronic pain patient with an implanted intrathecal pump. This is the first report describing labour analgesia in a patient with such a device. As intrathecal systems become more popular for the management of nonmalignant pain, this situation is likely to be encountered with increasing frequency in the future. CLINICAL FEATURES: The patient was a nulliparous 23-yr-old with a history of chronic hereditary pancreatitis whose intractable pain had been managed with intrathecal morphine 3 mg.day-1 via an implantable pump for four years. Inadequate time between presentation and onset of labour prevented us from using this system. Intravenous patient controlled analgesia with fentanyl using a bolus of 25 micrograms and a lockout of five minutes was ineffective and epidural analgesia using bupivacaine was initiated and resulted in satisfactory analgesia. CONCLUSION: The presence of an existing intrathecal delivery system does not preclude the use of supplemental epidural analgesia during labour.

Adult↗
PubMed1997

Quantitative assessment of whole body galactose metabolism in galactosemic patients.

We employed [1-13C] galactose in isotope kinetic studies to delineate whole body galactose metabolism in vivo in patients with galactose-1-phosphate uridyltransferase (GALT) deficiency. The data in three control and three adult galactosemic subjects, homozygous for the most common GALT gene defect, the Q188R mutation, and with absent RBC GALT activity, revealed an apparent endogenous galactose synthesis rate of 0.53-1.05 mg/kg per hour. Unlike normal children and adults who eliminated 3%-6% and 21%-47% of an intravenous bolus of [1-13C] galactose as 13CO, in expired air in 1 and 5 h respectively, classic galactosemic patients, either Q188R/Q188R or Q188R/unknown, released almost none in 1 h and 3%-6% in 5 h. In contrast, an African-American galactosemic variant patient with a S135L/S135L mutation and no residual RBC GALT activity oxidized [1-13C]galactose to 13CO2 at a rate comparable to control subjects. Individuals homozygous for the Duarte mutation, N314D/N314D and Q188R/ N314D. Q188R/+ and S135L/+ subjects also had normal breath test results. Not surprisingly, the Q188R/Q188R classic galactosemic patient cannot handle an acute galactose load, failing to match a control subject in the rapid conversion of [1-13C]galactose to [13C]glucose and 13CO2. However, classic patients synthesize substantial quantities of galactose de novo and on a lactose-free diet must oxidize comparable amounts of galactose to maintain steady-state levels of galactose and galactose metabolites such as galactose-1-phosphate, galactitol and galactonate. In vivo isotope kinetic analyses may allow us to understand better these aspects of galactose metabolism and, through the use of studies in variant galactosemics, perhaps allow us to begin to unravel the pathophysiology of galactosemia.

Adolescent↗
PubMed1997

Superiority of multi-orifice over single-orifice epidural catheters for labor analgesia and cesarean delivery.

STUDY OBJECTIVE: To investigate whether a change from a single-orifice to multi-orifice catheter could reduce the incidence of inadequate epidural blocks requiring replacement of the epidural catheter in obstetric patients. STUDY DESIGN: Prospective before-after cohort study. SETTING: Obstetric unit at a university hospital. PATIENTS: 872 patients requesting epidural analgesia for vaginal delivery or cesarean section. INTERVENTIONS: Patients received epidural analgesia via single-orifice (n = 433) or multi-orifice (n = 439) epidural catheters, depending on the month of the trial. MEASUREMENTS AND MAIN RESULTS: Patient characteristics, obstetric procedure, anesthesiologist characteristics, and details of epidural placement did not differ significantly between the groups. The overall replacement rate was 14.3% in the single-orifice group versus 9.3% in the multi-orifice group (p = 0.032). There were no difference in the frequency of replacement for subarachnoid placement or migration, immediate intravascular placement, vascular migration, or absence of any block. Significantly fewer catheters were replaced in the multi-orifice group for inadequate analgesia, defined as unblocked segments or unilateral block (6.4% vs. 2.8%, p = 0.018). Paresthesias were less common in the multi-orifice group (22.4% vs. 31.5%, p = 0.003). There were no unrecognized subarachnoid or vascular catheter placements in either group. CONCLUSIONS: The multi-orifice design offers significant advantages over the single-orifice type for obstetricepidural analgesia.

Adult↗
PubMed1997

Venous drainage of the inferolateral temporal lobe in relationship to transtemporal/transtentorial approaches to the cranial base.

OBJECTIVE: Intimate to the application of lateral transtemporal approaches to the cranial base are the identification, manipulation, and/or the sacrifice of the venous anatomy of the inferolateral temporal lobe and the superior petrosal sinus and the transection of the tentorium. This study demonstrates the relationship and variability of the venous drainage of the lateral and inferior surfaces of the temporal lobe. METHODS: Twenty-one specially prepared, injected cadaver specimens yielded 40 temporal lobes for examination. The venous systems in these specimens were traced from their origins on the temporal lobe (venous drainage complexes) to the transverse/petrosal sinuses, and the geometry of these venous complexes (venous configuration) was noted. The measurements of each complex's entry to the sinuses were noted. RESULTS: Four distinct venous drainage complexes were identified: 1) the lateral complex, 2) the anteroinferior complex, 3) the medial-inferior complex, and 4) the posteroinferior complex. Three basic venous configurations were found: 1) the candelabra of veins uniting to form one large draining vein, 2) multiple independent draining veins, and 3) venous lakes running in the tentorium before entering the sinuses. The lateral complex, incorporating the classic "vein of Labbé," was present in 100% of the specimens. However, in the majority of cases, it did not represent the dominant venous drainage of the lateral and inferior surfaces of the temporal lobe. CONCLUSION: An understanding of the complexity and diversity of the venous drainage complexes and their configurations is necessary to avoid venous complications during lateral cranial base surgery.

Cerebral Veins↗
PubMed1997

Function of the c-Myc antagonist Mad1 during a molecular switch from proliferation to differentiation.

Mad-Max heterodimers have been shown to antagonize Myc transforming activity by a mechanism requiring multiple protein-protein and protein-DNA interactions. However, the mechanism by which Mad functions in differentiation is unknown. Here, we present evidence that Mad functions by an active repression mechanism to antagonize the growth-promoting function(s) of Myc and bring about a transition from cellular proliferation to differentiation. We demonstrate that exogenously expressed c-Myc blocks inducer-mediated differentiation of murine erythroleukemia cells without disrupting the induction of endogenous Mad; rather, high levels of c-Myc prevent a heterocomplex switch from growth-promoting Myc-Max to growth-inhibitory Mad-Max. Cotransfection of a constitutive c-myc with a zinc-inducible mad1 results in clones expressing both genes, whereby a switch from proliferation to differentiation can be modulated. Whereas cells grown in N'N'-hexamethylene bisacetamide in the absence of zinc fail to differentiate, addition of zinc up-regulates Mad expression by severalfold and differentiation proceeds normally. Coimmunoprecipitation analysis reveals that Mad-Max complexes are in excess of Myc-Max in these cotransfectants. Moreover, we show that the Sin-binding, basic region, and leucine zipper motifs are required for Mad to function during a molecular switch from proliferation to differentiation.

Acetamides↗