Biomedical subjects

L Morin

Publications and source records attributed to L Morin.

At least 19 recordsLinked to original sources

PubMed2005

The role of radiotracer imaging in Parkinson disease.

Radiotracer imaging (RTI) of the nigrostriatal dopaminergic system is a widely used but controversial biomarker in Parkinson disease (PD). Here the authors review the concepts of biomarker development and the evidence to support the use of four radiotracers as biomarkers in PD: [18F]fluorodopa PET, (+)-[11C]dihydrotetrabenazine PET, [123I]beta-CIT SPECT, and [18F]fluorodeoxyglucose PET. Biomarkers used to study disease biology and facilitate drug discovery and early human trials rely on evidence that they are measuring relevant biologic processes. The four tracers fulfill this criterion, although they do not measure the number or density of dopaminergic neurons. Biomarkers used as diagnostic tests, prognostic tools, or surrogate endpoints must not only have biologic relevance but also a strong linkage to the clinical outcome of interest. No radiotracers fulfill these criteria, and current evidence does not support the use of imaging as a diagnostic tool in clinical practice or as a surrogate endpoint in clinical trials. Mechanistic information added by RTI to clinical trials may be difficult to interpret because of uncertainty about the interaction between the interventions and the tracer.

Biomarkers↗

PubMed2003

Obstetric implications of low-lying placentas diagnosed in the second trimester.

OBJECTIVES: To determine the obstetrical outcome of pregnancies initially complicated by a low-lying placenta in the second trimester. METHODS: We reviewed the obstetric outcome of all women with singleton deliveries from 1 January 1997 to 31 March 1999 and compared the 703 women with low-lying placentas (placentas in the lower uterine segment) with the 6938 women with placentas that were normally situated in the upper uterine segment at 16-22 weeks' gestation. RESULTS: Pregnancies complicated by a low-lying placenta in the second trimester were not associated with antepartum hemorrhage, preterm births, preterm prelabor rupture of membranes, pregnancy-induced hypertension, fetal growth restriction or cesarean births. However, they had a higher incidence of postpartum hemorrhage (odds ratio 1.768, 95% confidence interval 1.137, 2.748) than women with a normally situated placenta in the second trimester. CONCLUSIONS: Pregnant women with low-lying placentas in the second trimester have a higher incidence of postpartum hemorrhage and hence, it would be prudent to carefully manage the third stage of labor in these women.

Adult↗

PubMed2001

Tat1, a novel sulfate transporter specifically expressed in human male germ cells and potentially linked to rhogtpase signaling.

RhoGTPases (Rho, Rac, and Cdc42) are known to regulate multiple functions, including cell motility, adhesion, and proliferation; however, the signaling pathways underlying these pleiotropic effects are far from fully understood. We have recently described a new RhoGAP (GTPase activating protein for RhoGTPases) gene, MgcRacGAP, primarily expressed in male germ cells, at the spermatocyte stage. We report here the isolation, through two-hybrid cloning, of a new partner of MgcRacGAP, very specifically expressed in the male germ line and showing structural features of anion transporters. This large protein (970 amino acids and a predicted size of 109 kDa), we provisionally designated Tat1 (for testis anion transporter 1), is closely related to a sulfate permease family comprising three proteins in human (DRA, Pendrin, and DTD); it is predicted to be an integral membrane protein with 14 transmembrane helices and intracytoplasmic NH(2) and COOH termini. In situ hybridization studies demonstrate that Tat1 and MgcRacGAP genes are coexpressed in male germ cells at the spermatocyte stage. On testis sections, Tat1 protein can be immunodetected in spermatocytes and spermatids associated with plasma membrane. Two-hybrid and in vitro binding assays demonstrate that MgcRacGAP stably interacts through its NH(2)-terminal domain with the Tat1 COOH-terminal region. Expression of Tat1 protein in COS7 cells generates a 4,4'-diisothiocyano-2,2'-disulfonic acid stilbene and chloride-sensitive sulfate transport. Therefore we conclude that Tat1 is a novel sulfate transporter specifically expressed in spermatocytes and spermatids and interacts with MgcRacGAP in these cells. These observations raise the possibility of a new regulatory pathway linking sulfate transport to Rho signaling in male germ cells.

Amino Acid Sequence↗

PubMed2000

Determinants of unexplained antepartum fetal deaths.

OBJECTIVE: To assess fetal, maternal, and pregnancy-related determinants of unexplained antepartum fetal death. METHODS: We conducted a hospital-based cohort study of 84,294 births weighing 500 g or more from 1961-1974 and 1978-1996. Unexplained fetal deaths were defined as fetal deaths occurring before labor without evidence of significant fetal, maternal, or placental pathology. RESULTS: One hundred ninety-six unexplained antepartum fetal deaths accounted for 27.2% of 721 total fetal deaths. Two thirds of the unexplained fetal deaths occurred after 35 weeks' gestation. The following factors were independently associated with unexplained fetal death: maternal prepregnancy weight greater than 68 kg (adjusted odds ratio [OR] 2.9; 95% confidence interval [CI] 1.85, 4.68), birth weight ratio (defined as ratio of birth weight to mean weight for gestational age) between 0.75 and 0.85 (OR 2.77; 95% CI 1.48, 5.18) or over 1.15 (OR 2.36; 95% CI 1.26, 4.44), fewer than four antenatal visits in women whose fetuses died at 37 weeks or later (OR 2.21; 95% CI 1.08, 4.52), primiparity (OR 1.74; 95% CI 1.26, 2.40), parity of three or more (OR 2.01; 95% CI 1.26, 3.20), low socioeconomic status (OR 1.59; 95% CI 1.14, 2.22), cord loops (OR 1.75; 95% CI 1.04, 2.97) and, for the 1978-1996 period only, maternal age 40 years or more (OR 3.69; 95% CI 1.28, 10.58). Trimester of first antenatal visit, low maternal weight, postdate pregnancy, fetal-to-placental weight ratio, fetal sex, previous fetal death, previous abortion, cigarette smoking, and alcohol use were not significantly associated with unexplained fetal death. CONCLUSION: In this study, we identified several factors associated with an increased risk of unexplained fetal death.

Adult↗

PubMed2000

Protein feeding pattern does not affect protein retention in young women.

This study was undertaken to determine whether a pulse protein feeding pattern was more efficient than a spread pattern to improve protein anabolism in young women as was already shown in elderly women. After a 15-d adaptive period [1.2 g protein/(kg fat-free mass. d)], 16 young women (age 26 +/- 1 y) were given a 14-d diet providing 1.7 g protein/(kg fat-free mass. d), using either a pulse pattern (protein consumed mainly in one meal, n = 8), or a spread pattern (spreading daily protein intake over four meals, n = 8). Nitrogen balance was determined at the end of both the 15-d adaptive and the 14-d experimental periods. Whole-body protein turnover was determined at the end of the 14-d experimental period using [(15)N]glycine as an oral tracer. Nitrogen balance was 17 +/- 5 mg N/(kg fat-free mass. d) during the adaptive period. It was higher during the experimental period, but not significantly different in the women fed the spread or the pulse patterns [59 +/- 12 and 36 +/- 8 mg N/(kg fat-free mass. d) respectively]. No significant effects of the protein feeding pattern were detected on either whole-body protein turnover [5.5 +/- 0.2 vs. 6.1 +/- 0.3 g protein/(kg fat-free mass. d) for spread and pulse pattern, respectively] or whole-body protein synthesis and protein breakdown. Thus, in young women, these protein feeding patterns did not have significantly different effects on protein retention.

Adult↗

PubMed1999

Prenatal percutaneous needle drainage of cystic sacrococcygeal teratomas.

Prenatal ultrasound (US) permits in utero diagnosis of sacrococcygeal teratoma (SCT), follow-up of tumor size, and the early identification of complications, allowing for a more timely and appropriate delivery. The recommended management of large SCTs is delivery by cesarean section (CS) to prevent dystocia, tumor rupture, hemorrhage, and death. However, even delivery by CS can be difficult, necessitating a large hysterotomy that adds to maternal morbidity. The authors report two cases of cystic SCTs in which prenatal percutaneous drainage allowed for an uncomplicated vaginal delivery. In the first case, a large unilocular cystic SCT was diagnosed at 31 weeks' gestation on prenatal US. The fetal presentation was breech, and the mass was steadily increasing in size, preventing spontaneous version. At 37 5/7 weeks, the cyst was percutaneously drained under US guidance allowing for successful external version. Repeat drainage just before induction of labor permitted a successful vaginal delivery. In the second case, the cystic SCT was percutaneously drained just before induction of labor at full term, again allowing for an uncomplicated vaginal delivery. Prenatal percutaneous needle drainage of cystic SCTs offers an alternative to CS that results in decreased risks for both mother and fetus.

Adult↗

PubMed1999

Messenger RNA in dormant cells of Sterkiella histriomuscorum (Oxytrichiade): indentification of putative regulatory gene transcripts.

In the absence of food, the oxytrichid Sterkiella histriomuscorum, like many ciliates, enters into dormancy and transforms into a round and walled encysted cell. When transferred back into a feeding medium, the cyst re-transforms into a vegetative cell in a few hours. This encystment-excystment pathway, which is common to many free-living and parasitic protists, is still poorly understood at the molecular level. In order to identify potential dormant transcripts in the cysts of Sterkiella, we have constructed cDNA libraries from mature cysts. Transcripts have been isolated confirming the presence of a mRNA pool in the dormant cells. The sequence analysis of two cDNA indicates open reading frames which show significant similarities to known proteins involved in mechanisms of regulation: 1) nifR3, an element of the nitrogen regulatory system in bacteria and 2) CROC-1, a newly identified human transcription factor. The two corresponding macronuclear genes represent the first putative regulatory genes isolated in ciliates. From a differential screening of the cDNA library against vegetative cDNA, one cyst-specific (and very abundant) transcript has been isolated but the product has not yet been identified. The possible involvment of these new ciliate genes in the excystment process is discussed.

Amino Acid Sequence↗

PubMed1999

Protein pulse feeding improves protein retention in elderly women.

BACKGROUND: Adequate protein nutrition could be used to limit gradual body protein loss and improve protein anabolism in the elderly. OBJECTIVE: We tested the hypothesis that an uneven protein feeding pattern was more efficient in improving protein anabolism than was an even pattern. DESIGN: After a controlled period, 15 elderly women (mean age: 68 y) were fed for 14 d either a pulse diet (n = 7), providing 80% of the daily protein intake at 1200, or a spread diet (n = 8), in which the same daily protein intake was spread over 4 meals. Both diets provided 1.7 g protein x kg fat-free mass (FFM)(-1) x d(-1). Protein accretion and daily protein turnover were determined by using the nitrogen balance method and the end product method (ammonia and urea) after an oral dose of [15N]glycine. RESULTS: Nitrogen balance was more positive with the pulse than with the spread diet (54 +/- 7 compared with 27 +/- 6 mg N x kg FFM(-1) x d(-1); P < 0.05). Protein turnover rates were also higher with the pulse than with the spread diet (5.58 +/- 0.22 compared with 4.98 +/- 0.17 g protein x kg FFM(-1) x d(-1); P < 0.05), mainly because of higher protein synthesis in the pulse group (4.48 +/- 0.19 g protein x kg FFM(-1) x d(-1)) than in the spread group (3.75 +/- 0.19 g protein x kg FFM(-1) x d(-1)) (P < 0.05). CONCLUSION: A protein pulse-feeding pattern was more efficient than was a protein spread-feeding pattern in improving, after 14 d, whole-body protein retention in elderly women.

Aged↗

PubMed1998

Secular trends in preterm birth: a hospital-based cohort study.

CONTEXT: Canada and the United States have reported a recent increase in the incidence of preterm birth, but the reasons for this increase are unknown. OBJECTIVE: To assess secular trends in preterm birth and its potential determinants. DESIGN: Hospital-based cohort study. SETTING: Canadian tertiary care university teaching hospital, 1978-1996. PARTICIPANTS: A total of 65574 nonreferred live births and stillbirths. MAIN OUTCOME MEASURES: Changes in occurrence of preterm birth, before and after adjustment for changes in method of gestational age assessment, obstetric intervention, registration of births weighing less than 500 g, and sociodemographic, behavioral, and clinical determinants. RESULTS: A crude secular increase in preterm births was seen for births less than 37, 34, and 32 completed weeks using 3 alternative gestational age estimation methods. Based on an algorithm incorporating both menstrual and early ultrasound gestational age estimates, rates increased from 6.6% to 9.8% for births at less than 37 weeks' gestation, 1.7% to 2.3% at less than 34 weeks, and 1.0% to 1.2% at less than 32 weeks. Exclusion of births weighing less than 500 g and those with induction or preterm cesarean delivery without labor before each of the corresponding gestational age cutoffs eliminated the secular trends for births before 34 and 32 weeks and attenuated the trend for births before 37 weeks. Nearly half of the remaining trend for births before 37 weeks was accounted for by the increasing use of early ultrasound dating. The residual trend was eliminated after controlling for secular increases in unmarried status and the proportion of women aged 35 years or older. These factors, combined with a decrease in alcohol consumption and increases in histological chorioamnionitis and cocaine use, appear to have counteracted a reduction in preterm birth since the mid-1980s that otherwise would have been observed. CONCLUSIONS: This hospital's increase in preterm births since 1978 parallels increases reported in population-based national studies from the United States and Canada. This trend appears largely attributable to the increasing use of early ultrasound dating, preterm induction and preterm cesarean delivery without labor, and changes in sociodemographic and behavioral factors.

Canada↗

PubMed1998

MgcRacGAP, a new human GTPase-activating protein for Rac and Cdc42 similar to Drosophila rotundRacGAP gene product, is expressed in male germ cells.

In a search for new partners of the activated form of Rac GTPase, we have isolated through a two-hybrid cloning procedure a human cDNA encoding a new GTPase-activating protein (GAP) for Rho family GTPases. A specific mRNA of 3.2 kilobases was detected in low abundance in many cell types and found highly expressed in testis. A protein of the predicted size 58 kDa, which we call MgcRacGAP, was detected in human testis as well as in germ cell tumor extracts by immunoblotting with antibodies specific to recombinant protein. In vitro, the GAP domain of MgcRacGAP strongly stimulates Rac1 and Cdc42 GTPase activity but is almost inactive on RhoA. N-terminal to its GAP domain, MgcRacGAP contains a cysteine-rich zinc finger-like motif characteristic of the Chimaerin family of RhoGAPs. The closest homolog of MgcRacGAP is RotundRacGAP, a product of the Drosophila rotund locus. In situ hybridization experiments in human testis demonstrate a specific expression of mgcRacGAP mRNA in spermatocytes similar to that of rotundRacGAP in Drosophila testis. Therefore, protein sequence similarity and analogous developmental and tissue specificities of gene expression support the hypothesis that RotundRacGAP and MgcRacGAP have equivalent functions in insect and mammalian germ cells. Since rotundRacGAP deletion leads to male sterility in the fruit fly, the mgcRacGAP gene may prove likewise to play a key role in mammalian male fertility.

Amino Acid Sequence↗

PubMed1998

How small is too small in a twin pregnancy?

OBJECTIVE: The objective was to determine whether small twins had a survival advantage with respect to small singletons after controlling for other factors associated with adverse perinatal outcome. STUDY DESIGN: A hospital-based cohort study included all births between 1980 and 1995 of babies born between 24 and 43 weeks' gestation. Logistic regression was used to estimate the perinatal mortality risks for monochorionic and dichorionic twins with growth restriction after adjusting for gestational age, maternal age, parity, method of delivery, and the presence or absence of congenital malformations. RESULTS: The study sample included 1062 dichorionic twins, 354 monochorionic twins, and 59,873 singletons. Small monochorionic and dichorionic twins showed a similar overall risk of perinatal mortality (odds ratio 1.40, confidence interval 0.86 to 2.25). However, monochorionic twins with birth weights <10th percentile faced an increased risk of perinatal death compared with singletons (odds ratio 2.45, confidence interval 1.20 to 5.02). Dichorionic twins had no such increased risk (odds ratio 0.91, confidence interval 0.45 to 1.84). CONCLUSIONS: Twins with growth restriction are not protected against perinatal loss, even after adjusting for congenital malformations. In fact, monochorionic twins are more than twice as likely to die in the perinatal period as are their singleton counterparts.

Cohort Studies↗

PubMed1997

Enhanced apoptosis in the thymus of transgenic mice expressing constitutively activated forms of human Rac2GTPase.

Rac proteins constitute a subgroup of the Rho family of small GTPases and include Rac1, which is expressed ubiquitously, and Rac2, a highly homologous protein only expressed in myelo-monocytic and lymphoid cell lineages. In fibroblasts, Rac1 plays a crucial role in control of actin cytoskeleton organisation, cell growth and Ras-induced transformation. In phagocytes, Rac1 and Rac2 regulate a specific enzymatic complex, NADPH oxidase. These multiple functions have been ascribed to Rac proteins only on the basis of cell culture and in vitro biochemical studies. To examine the role of Rac2 in vivo in a T cell lineage, we have expressed either wild-type or constitutively-activated forms of human Rac2 (Rac2V12 and Rac2L61) in transgenic mice under control of the thymus specific lck proximal promoter. We report here a striking atrophy of the thymus in mice expressing even low levels of either of the activated mutants of Rac2, while expression of Rac2wt has no effect. This phenotype is correlated with a marked decrease in the number of double positive (CD4+ CD8+) and single positive (CD4+ CD8- and CD8+ CD4-) thymocytes. Cellular and molecular analyses demonstrate that this defect is due to an increase in apoptosis among thymocytes. As Rac2 is normally expressed in thymocytes and activated T cells, we propose that Rac2 dependent pathways could play an important role in control of growth and death of T cells.

Animals↗

PubMed1997

Impaired phosphoinositide metabolism in glucose-incompetent islets of neonatally streptozotocin-diabetic rats.

The effects of nutrient and neurotransmitter stimuli on insulin release, loss of phosphoinositides (PI), and production of inositol phosphates (InsP) were investigated in islets from neonatally streptozotocin-injected (nSTZ) rats. In islets from nSTZ rats, insulin secretory responses to 16.7 mM D-glucose and 10.0 mM D-glyceraldehyde were reduced compared with controls. Contents in phosphatidylinositol 4-monophosphate [PtdIns(4)P] and phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2], but not in phosphatidylinositol, were diminished. Glucose effects on breakdown of PtdIns(4)P and PtdIns(4,5)P2 and on total InsP accumulation were both reduced. D-Glucose was unable to increase the levels of both inositol trisphosphate isomers, Ins(1,3,4)P3 and Ins(1,4,5)P3. Glyceraldehyde also failed to promote InsP formation. By contrast, the ability of 1.0 mM carbachol or 300 nM cholecystokinin to stimulate insulin secretion and InsP generation was still observed. Thus a disturbed coupling between nutrient recognition and activation of phospholipase C, possibly together with a shortage of available polyphosphoinositides, could be responsible for the altered islet PI turnover in the nSTZ rats. It is proposed that such defects may contribute to the impairment of glucose-stimulated insulin secretion in this model of non-insulin-dependent diabetes mellitus.

Animals↗

PubMed1996

Decreased ATP-induced synthesis and Ca(2+)-stimulated degradation of polyphosphoinositides in pancreatic islets from neonatally streptozotocin-diabetic rats.

Phosphoinositide (PI) synthesis and hydrolysis were investigated in pancreatic islet homogenates from neonatal streptozotocin diabetic (n-STZ) and control rats. In the diabetics, ATP, in absence of Ca2+, failed to increase the amount of phosphatidylinositol 4-phosphate (PtdInsP) and phosphatidyl inositol 4, 5-bisphosphate (PtdInsP2) at variance with the pattern in controls. Also, the Ca(2+)-stimulated generation of inositol phosphates (InsP) was dramatically decreased, whether in the absence or presence of ATP. Moreover, phosphatidylinositol (PtdIns) kinase activity was reduced while PtdInsP kinase activity was not impaired. These data suggest that the suppressed formation of PtdInsP and subsequent PtdInsP2 synthesis, concomitantly with a decreased Ca(2+)-stimulated phospholipase C activity, may participate to the alteration of the PI pathway, the limitation of the InsP production, and finally the impairment of the insulin release in the n-STZ model of non-insulin-dependent diabetes.

1-Phosphatidylinositol 4-Kinase↗

PubMed1996

Minimal hydronephrosis in the fetus: clinical significance and implications for management.

PURPOSE: We further define the natural history and management of minimal fetal hydronephrosis. MATERIALS AND METHODS: Experience with minimal fetal hydronephrosis (renal pelvic diameter 4 to 10 mm. before 20 weeks of gestation and 5 to 10 mm. from 20 to 24 weeks) was reviewed for 18 months at New England Medical Center. RESULTS: The incidence of minimal fetal hydronephrosis was 2.2% in the 5,900 fetuses screened by ultrasound. In 63% of cases prenatal ultrasound was done more than once, and revealed that dilatation of the urinary tract was stable during gestation in 31 (25%), and became normal in 35 (29%) and worse in 11 (9%). A total of 63 patients (103 renal units) followed for up to 1 year underwent postnatal sonography. Those with abnormalities were screened with a voiding cystourethrogram and renal scan, including 40 with normal postnatal ultrasound and no changes on subsequent evaluation. Of the 23 patients with abnormal findings 4 had functionally significant ureteropelvic junction obstruction and 1 had severe vesicoureteral reflux. A retrospective analysis of the sonograms of patients with minimal fetal hydronephrosis and persistence or progression of hydronephrosis revealed calicectasis, progression of minimal fetal hydronephrosis in utero and/or abnormal renal echogenicity in each fetus. CONCLUSIONS: Our study shows that in a small but significant number of fetuses minimal fetal hydronephrosis will progress, whereas in most it will resolve.

Disease Progression↗

PubMed1994

Modulation of stress proteins by Cd2+ in a human T cell line.

We previously showed in a human T cell line (CEM-C12 cells) that Cd2+ induced gene expression of stress proteins, metallothionein-IIA and heat shock protein 70 in a time- and dose-dependent manner. In the present study, CEM-C12 cells were pretreated for 24 h with 1 microM Cd2+ and then challenged with toxic concentrations of this metal. We found that maximal expression of the metallothionein-IIA and heat shock protein 70 genes was increased and this maximal level occurred at higher Cd2+ toxic concentrations. Actinomycin D chase experiments indicated that Cd2+ pretreatment did not modify metallothionein-IIA mRNA stability. The modulatory effect of Cd2+ pretreatment was dose-dependent from 100 pM to 1 microM. Such pretreatment also enhanced resistance to Cd2+ toxicity. Finally, verapamil, a calcium/potassium channel blocker displaced the dose-response curve for Cd2+ toxicity as well as metallothionein-IIA and heat shock protein 70 gene expression to higher Cd2+ concentrations.

Blotting, Northern↗

PubMed1994

[Deinstitutionalization of severely mentally retarded patients: impact on prescription of neuroleptics].

The neuroleptic medication prescribed over a period of 12 years for three groups of severely developmentally handicapped patients is analyzed retrospectively. The average daily doses prescribed for two groups of patients, deinstitutionalized either to foster homes or group homes, are compared to those prescribed for a third group of patients who were not deinstitutionalized. The results show that deinstitutionalization had no impact on the prescribing of neuroleptics, regardless of the type of residence: group home or foster home. The results show, moreover, that for the three groups of patients, time spent without medication decreased significantly over the 12 years of this study. These results are discussed in relation to the problem of the patients' social reintegration into the community.

Adult↗

PubMed1994

Bronchopulmonary sequestration: prenatal diagnosis with clinicopathologic correlation.

A patient was referred at 21 weeks' gestation for evaluation of an echogenic mass in the fetal right chest. Color-doppler sonography facilitated the diagnosis of a bronchopulmonary sequestration. Clinicopathologic correlation was possible after termination at 2.3 weeks' gestation. Pathologic examination confirmed the prenatal diagnosis and demonstrated the systemic vascular supply seen on color-doppler sonography. Color doppler is a useful adjunct in the sonographic evaluation of the fetus with an echogenic chest mass.

Adult↗