Search PubMed⌕ Search

Biomedical subjects

C B Martin

Publications and source records attributed to C B Martin.

At least 19 recordsLinked to original sources
PubMed2001

The thrombin receptor, PAR-1, causes transformation by activation of Rho-mediated signaling pathways.

We utilized a cDNA expression library derived from the B6SutA(1) mouse myeloid progenitor cell line to search for novel oncogenes that promote growth transformation of NIH3T3 cells. A 2.2 kb transforming cDNA was recovered that encodes the wild type thrombin-stimulated G protein-coupled receptor PAR-1. In addition to its potent focus forming activity, constitutive overexpression of PAR-1 in NIH3T3 cells promoted the loss of anchorage- and serum-dependent growth. Although inhibitors of thrombin failed to block PAR-1 transforming activity, a PAR-1 mutant that cannot be cleaved by thrombin was nontransforming. Since the foci of transformed cells induced by PAR-1 bear a striking resemblance to those induced by activated RhoA, we determined if PAR-1 transformation was due to the aberrant activation of a specific Rho family member. Like RhoA, PAR-1 cooperated with activated Raf-1 and caused synergistic enhancement of transforming activity, induced stress fibers when microinjected into porcine aortic endothelial cells, stimulated the activity of the serum response factor and NF-kappaB transcription factors, and PAR-1 transformation was blocked by co-expression of dominant negative RhoA. Finally, PAR-1 transforming activity was blocked by pertussis toxin and by co-expression of the RGS domain of Lsc, implicating Galpha(i) and Galpha(12)/Galpha(13) subunits, respectively, as mediators of PAR-1 transformation. Taken together, these observations suggest that PAR-1 growth transformation is mediated, in part, by activation of RhoA.

3T3 Cells↗
PubMed2000

Assessment of fetal rhythm in complete congenital heart block by magnetocardiography.

We report high precision assessment of fetal rhythm in utero in a case of isolated congenital complete heart block using fetal magnetocardiography. The recordings reveal a remarkably strong tendency for the atria and ventricles to synchronize, which is manifested by the continual presence of ventriculophasic sinus arrhythmia and frequent episodes of accrochage and isorhythmic AV dissociation.

Adult↗
PubMed1999

M-Ras/R-Ras3, a transforming ras protein regulated by Sos1, GRF1, and p120 Ras GTPase-activating protein, interacts with the putative Ras effector AF6.

M-Ras is a Ras-related protein that shares approximately 55% identity with K-Ras and TC21. The M-Ras message was widely expressed but was most predominant in ovary and brain. Similarly to Ha-Ras, expression of mutationally activated M-Ras in NIH 3T3 mouse fibroblasts or C2 myoblasts resulted in cellular transformation or inhibition of differentiation, respectively. M-Ras only weakly activated extracellular signal-regulated kinase 2 (ERK2), but it cooperated with Raf, Rac, and Rho to induce transforming foci in NIH 3T3 cells, suggesting that M-Ras signaled via alternate pathways to these effectors. Although the mitogen-activated protein kinase/ERK kinase inhibitor, PD98059, blocked M-Ras-induced transformation, M-Ras was more effective than an activated mitogen-activated protein kinase/ERK kinase mutant at inducing focus formation. These data indicate that multiple pathways must contribute to M-Ras-induced transformation. M-Ras interacted poorly in a yeast two-hybrid assay with multiple Ras effectors, including c-Raf-1, A-Raf, B-Raf, phosphoinositol-3 kinase delta, RalGDS, and Rin1. Although M-Ras coimmunoprecipitated with AF6, a putative regulator of cell junction formation, overexpression of AF6 did not contribute to fibroblast transformation, suggesting the possibility of novel effector proteins. The M-Ras GTP/GDP cycle was sensitive to the Ras GEFs, Sos1, and GRF1 and to p120 Ras GAP. Together, these findings suggest that while M-Ras is regulated by similar upstream stimuli to Ha-Ras, novel targets may be responsible for its effects on cellular transformation and differentiation.

3T3 Cells↗
PubMed1999

TC21 and Ras share indistinguishable transforming and differentiating activities.

Constitutively activated mutants of the Ras-related protein TC21/R-Ras2 cause tumorigenic transformation of NIH3T3 cells. However, unlike Ras, TC21 fails to bind to and activate the Raf-1 serine-threonine kinase. Thus, whereas Ras transformation is critically dependent on Raf-1 TC21 activity is promoted by activation of Raf-independent signaling pathways. In the present study, we have further compared the functions of Ras and TC21. First we determined the basis for the inability of TC21 to activate Raf-1. Whereas Ras can interact with the two distinct Ras-binding sequences in NH2-terminus of Raf-1, designated RBS1 and Raf-Cys, TC21 could only bind Raf-Cys. Thus, the inability of TC21 to bind to RBS1 may prevent it from promoting the translocation of Raf-1 to the plasma membrane. Second, we found that TC21 is an activator of the JNK and p38, but not ERK, mitogen-activated protein kinase cascades and that TC21 transforming activity was dependent on Rac function. Thus, like Ras, TC21 may activate a Rac/JNK pathway. Third, we determined if TC21 could cause the same biological consequences as Ras in three distinct cell types. Like Ras, activated TC21 caused transformation of RIE-1 rat intestinal epithelial cells and terminal differentiation of PC12 pheochromocytoma cells. Finally, activated TC21 blocked serum starvation-induced differentiation of C2 myoblasts, whereas dominant negative TC21 greatly accelerated this differentiation process. Therefore, TC21 and Ras share indistinguishable biological activities in all cell types that we have evaluated. These results support the importance of Raf-independent pathways in mediating the actions of Ras and TC21.

3T3 Cells↗
PubMed1999

Noninvasive in utero assessment of PR and QRS intervals from the fetal magnetocardiogram.

Fetal cardiac waveform intervals were assessed from fetal magnetocardiogram (FMCG) recordings taken from 59 pregnant women at 17-41 weeks gestation. Beyond 27 weeks' gestation PR and QRS intervals, measured from averaged waveforms, could be obtained from all subjects; however, prior to 21 weeks' gestation the success rate was 50% or less due to low signal-to-noise ratio. QT interval could not be assessed accurately in most subjects. Weak, but statistically significant, correlations with gestational age were found for PR interval (n = 145, R2 = 0.033, P = 0.028) and QRS interval (n = 145, R2 = 0.140, P < 0.0005). Abnormal waveform morphology was documented in several patients with cardiac malformations.

Adult↗
PubMed1998

Getting key players to work together and defending against diversion--California.

In 1988, Californians passed Proposition 99, which raised the tobacco tax from 10 cents to 35 cents and allocated 20% of the resulting revenues, approximately $100 million, for tobacco education and 5% for tobacco-related research. Seventy percent was allocated for health care costs and 5% for the environment. In this report, the authors provide an overview of the process of implementing the tobacco education program, which is followed by a more detailed review and analysis of the major impediments to the program, i.e., the diversion of a significant portion of the funding voters had earmarked for tobacco education and research and the battles for legislative reauthorization of Proposition 99 in the 1990s.

California↗
PubMed1998

Electronic fetal monitoring: a brief summary of its development, problems and prospects.

Electronic fetal monitoring (EFM) was introduced into clinical practice 30 years ago and spread very rapidly in most developed countries. The early optimism that EFM would lead to a marked reduction in fetal neurological injury has not been realized; however, it is now recognized that most such damage is unrelated to perinatal events. Clinical trials have shown that although EFM does reduce the incidence of intrapartum asphyxia, its use is also associated with an increase in cesarean sections. Abnormal fetal heart rate (FHR) patterns are poor predictors of fetal depression at birth when used without additional confirmatory information. An additional problem has been inconsistency in the interpretation of EFM tracings even among experts. This has reduced the clinical effectiveness of EFM and has also contributed to an increase in litigation in cases with adverse neonatal outcomes. Despite these shortcomings EFM continues to be used extensively on most obstetrical services, suggesting that obstetrical physicians and nurses find the technique helpful and will continue to use it until a better alternative comes along. The combination of relevant clinical data with EFM by means of intelligen computer systems may improve both the consistency and predictive value of intrapartum fetal assessment in the future.

Animals↗
PubMed1997

Reversible fetal hydrops associated with indomethacin use.

BACKGROUND: Ductus arteriosus constriction is a known complication of exposure to indomethacin in utero. Nonimmune hydrops associated with indomethacin use has been reported in only six cases, all twins over 32 weeks' gestation. CASE: We present a case of fetal hydrops associated with tricuspid regurgitation and ductal constriction developing within 30 hours of instituting indomethacin tocolysis in a 28-week singleton gestation. Discontinuation of indomethacin resulted in partial resolution of these findings 72 hours later. A normal infant was delivered subsequently. CONCLUSION: Ultrasonographic screening for signs of constriction of the ductus arteriosus should be done within 48 hours of instituting indomethacin therapy at any gestational age.

Adult↗
PubMed1996

Analysis of the gene that encodes the complement regulatory protein, membrane inhibitor of reactive lysis (CD59). Identification of an alternatively spliced exon and characterization of the transcriptional regulatory regions of the promoter.

Membrane inhibitor of reactive lysis (MIRL, CD59) is an 18-kDa glycosylphosphatidylinositol-anchored protein that regulates formation of the membrane attack complex of complement. The purpose of these studies was to characterize the gene that encodes CD59. Our experiments redefined the structural organization of the gene by identifying a previously unrecognized alternatively spliced exon. Analysis by PCR of cDNA derived from a variety of cultured human cell lines and from PBMC showed that transcripts containing the alternatively spliced exon sequence were expressed concordantly with transcripts lacking that sequence. Primer extension studies demonstrated that the transcriptional start site of alternatively spliced CD59 mRNA is the same as that of transcripts without the alternatively spliced exon sequence, suggesting that expression of both forms of CD59 mRNA is regulated similarly. Analysis of the promoter region showed that the first 70 nucleotides immediately 5' of the transcriptional start site of the CD59 gene are essential for both constitutive and PMA-responsive transcription; however, responsiveness to PMA is cell line specific. Together, these studies have redefined the organization of the CD59 gene and identified regions of the promoter involved in constitutive and PMA-inducible transcription.

Antigens, Neoplasm↗
PubMed1996

Binding specificity and mutational analysis of the phosphotyrosine binding domain of the brain-specific adaptor protein ShcC.

Shc proteins (hereafter referred to as ShcA) represent major substrates of tyrosine phosphorylation by a wide variety of growth factors and cytokines. We have recently described a novel ShcA-like protein, ShcC, which like ShcA contains an NH2-terminal phosphotyrosine binding domain (PTB), a central effector region (CH1) and a COOH-terminal Src homology 2 domain (SH2). Both the SH2 and PTB domains of ShcC bind a similar profile of proteins as the comparable regions of ShcA. In an effort to define the functional differences or similarities between ShcA and ShcC, we have further characterized the PTB domain of ShcC. Using a degenerate phosphopeptide library screen, we show that the PTB domain of ShcC preferentially binds the sequence His-hydrophobic-Asn/hydrophobic-Asn-Pro-Ser/Thr-Tyr(P). This sequence is similar to the binding site for the ShcA PTB domain, suggesting that these two proteins may have overlapping specificities. In addition, random mutagenesis of the ShcC PTB domain has identified several amino acids important for PTB function (Gly32, Glu63, Ala136, Gly139, and Asp140). Mutation of these amino acids dramatically reduces the affinity of the ShcC PTB domain for the activated epidermal growth factor receptor in vitro.

Amino Acid Sequence↗
PubMed1996

Accuracy of maternal perception of preterm uterine activity.

OBJECTIVE: Our purpose was to compare the accuracy of maternal perception of preterm uterine activity by self-palpation versus home uterine activity monitoring. STUDY DESIGN: A total of 72,962 uterine activity records of 778 women receiving home uterine activity monitoring services were analyzed. Simultaneously with home uterine activity monitoring, the women indicated by an electronic marker when they felt a "contraction" through self-palpation. The perceptions of the women were compared to the tocodynamometrically measured uterine activity. RESULTS: Using self-palpation, women correctly identified 17.2% of contractions recorded by tocodynamometry. Overall mean percent correct correlation per patient was only 14.1%. Patients missed an average of 85.7% of their contractions. Patients incorrectly perceived contractions that were not present an average of 40.3% of the time. Singleton gestations had significantly better correct correlations than twin gestations. Multiparous women had improved correlations compared with primiparous women. No significant correlation was found between maternal perceptive ability and gestational age. CONCLUSION: Women were unable to perceive accurately the presence or absence of preterm uterine activity through self-palpation compared with simultaneous measurement by home uterine tocodynamometry.

Adult↗
PubMed1996

Perinatal and health care management consequences of twice-a-day versus once-a-day evaluation of home uterine activity monitoring data.

There was a significant increase in the number of physician interventions (additional testing of mother or baby; extra office, emergency, or labor and delivery unit visits; and especially extra hospitalizations) but no significant difference in perinatal outcome (illness in mother or baby) when women at high-risk for preterm labor on home uterine activity monitoring services had scheduled twice-a-day review (BID review) of the home uterine activity monitoring data they had collected versus once-a-day review (OD review).

Adult↗
PubMed1995

Foetal magnetocardiogram amplitude oscillations associated with respiratory sinus arrhythmia.

We show that oscillations at foetal breathing frequencies observed in foetal heart rate (FHR) tracings obtained from foetal magnetocardiogram (FMCG) recordings are often accompanied by synchronous modulation of FMCG signal amplitude. This implies an association between the FHR oscillations and foetal chest wall movements, corroborating the hypothesis that the oscillations are due to respiratory sinus arrhythmia.

Adult↗
PubMed1994

Spatiotemporal properties of the fetal magnetocardiogram.

OBJECTIVE: Our purpose was to investigate the spatiotemporal properties of the fetal magnetocardiogram. STUDY DESIGN: Fetal magnetocardiogram maps were measured for the first time in 20 subjects from 22 to 39 weeks' gestation. Waveform and topographic maps were used to display the data. RESULTS: The maps showed spatiotemporal properties consistent with simple volume conductor theory: topography was closely related to the presentation of the fetus, Q-wave sources were dipolar and localized, the magnetic heart vector rotated extensively during the QRS complex, and close correspondence was observed between fetal and neonatal maps. Ventricular depolarization and events in the cardiac cycle could be visualized in considerable detail by means of a time series of topographic maps. CONCLUSION: Fetal magnetocardiogram shows excellent spatiotemporal properties and is well suited for in utero studies of fetal heart activity.

Electrocardiography↗
PubMed1993

Spectral analysis of antepartum fetal heart rate variability from fetal magnetocardiogram recordings.

Fetal heart rate variability was derived from fetal magnetocardiogram recordings in ten subjects at gestation ages 32-38 weeks. Maternal interference was negligible and R-wave detection was highly reliable. Oscillations suggestive of respiratory sinus arrhythmia (RSA) were prominent in many of the heart rate tracings. Spectral analysis was used to quantify heart rate variability and to examine the influence of the RSA-like oscillations on heart rate variability. The oscillations were associated with increased power in the frequency range 0.4-1.0 Hz (P < or = 0.05). Magnetic recording appears to offer significant advantages for investigation of beat-to-beat fetal heart rate throughout the latter stages of pregnancy.

Adult↗
PubMed1993

Enhanced expression of the complement regulatory protein, membrane inhibitor of reactive lysis (CD59), is regulated at the level of transcription.

The membrane inhibitor of reactive lysis (MIRL) is an 18-Kd glycosyl phosphatidylinositol anchored membrane glycoprotein that inhibits the cytolytic activity of complement. MIRL is expressed by all hematopoietic elements and by a wide variety of nonhematopoietic tissues. A deficiency of MIRL is primarily responsible for the greater sensitivity of the erythrocytes of paroxysmal nocturnal hemoglobinuria to complement mediated lysis. Because of its critical role in protecting host cells from injury by complement, we hypothesized that mechanisms exist that allow MIRL expression to be regulated. To investigate this hypothesis, both MIRL RNA and MIRL protein expression were analyzed following exposure of K562 erythroleukemia cells to a variety of potential stimulants. Incubation with dexamethasone, calcium ionophore, lipopolysaccharide, interleukin 1, tumor necrosis factor, hemin, and cyclic AMP had no effect on MIRL expression. However, incubation with phorbol 12-myristate 13 acetate (PMA), induced a marked increase in MIRL RNA as determined by Northern blot analysis. This enhanced expression of MIRL RNA was associated with an increase in MIRL protein expression as determined by immunoprecipitation of metabolically labeled proteins, Western blot analysis, and immunobinding assay. Enhanced MIRL RNA expression was first detected after 8 hours and increased through 24 hours of observation. Inhibitors of either protein synthesis or transcription abrogated the PMA-induced enhancement of MIRL RNA expression. Together, these results are consistent with a model in which PMA induces synthesis of a trans acting protein that enhances transcription of the MIRL gene.

Antigens, CD↗