Biomedical subjects

L Lo

Publications and source records attributed to L Lo.

At least 19 recordsLinked to original sources

PubMed1999

Specification of neurotransmitter identity by Phox2 proteins in neural crest stem cells.

We have investigated the specification of noradrenergic neurotransmitter identity in neural crest stem cells (NCSCs). Retroviral expression of both wild-type and dominant-negative forms of the paired homeodomain transcription factor Phox2a indicates a crucial and direct role for this protein (and/or the closely related Phox2b) in the regulation of endogenous tyrosine hydroxylase (TH) and dopamine-beta hydroxylase (DBH) gene expression in these cells. In collaboration with cAMP, Phox2a can induce expression of TH but not of DBH or of panneuronal genes. Phox2 proteins are, moreover, necessary for the induction of both TH and DBH by bone morphogenetic protein 2 (BMP2) (which induces Phox2a/b) and forskolin. They are also necessary for neuronal differentiation. These data suggest that Phox2a/b coordinates the specification of neurotransmitter identity and neuronal fate by cooperating environmental signals in sympathetic neuroblasts.

Adrenal Glands↗

PubMed1999

A prospective randomized study comparing hysteroscopy and curettage (H & C) under local anaesthesia (LA) and general anaesthesia (GA) in Chinese population.

OBJECTIVE: To compare the difference in patient's acceptance of local anaesthesia (LA) and general anaesthesia (GA) hysteroscopy and curettage in Chinese population. DESIGN: A prospective randomized study. SUBJECTS AND METHODS: In the period September 1994 to August 1995, all Chinese women with abnormal uterine bleeding or suspected uterine anomaly who warranted hysteroscopy and uterine curettage were invited to participate in this study with informed consent. They were randomly allocated to the control (i.e. GA) and study (i.e. LA) group. RESULTS: Overall 90% of the controls and 91% of the study group were satisfied with the procedure. The hysteroscopic diagnostic accuracy was 83%. Significantly higher percentage of patients in the study group opted for the same form of admission arrangement if given the choice. CONCLUSION: Hysteroscopy and curettage under LA and GA are equally acceptable in the Chinese population in Hong Kong. The patient satisfaction rate is high in both groups. Hysteroscopic diagnosis is highly accurate in malignant condition (100% sensitivity and 83% specificity).

Adolescent↗

PubMed1999

Tubal ectopic pregnancy: an evaluation of laparoscopic surgery versus laparotomy in 614 patients.

We performed a prospective nonrandomized multicentre study to compare laparoscopic surgery and laparotomy in the immediate surgical outcome of tubal ectopic pregnancy (TEP), at 9 teaching hospitals in Hong Kong with a laparoscopic surgical service, on all patients with the operative diagnosis of tubal ectopic pregnancy between July 1, 1996 and June 30, 1997. In the period studied, 630 patients were recruited of which 614 were suitable for analysis. In them, 382 (62.2%) had laparoscopic surgery while the rest had laparotomy with or without diagnostic laparoscopy. Significantly more cases of shock ended in laparotomy (86.1% versus 13.9%). After exclusion of patients with shock, laparoscopic surgery offered a significantly shorter postoperative hospital stay (mean 2.7 days versus 5.3 days), a slightly lower perioperative complication rate (8.1% versus 13.9%) and more conservative surgery (90.1% of all salpingotomies) than laparotomy. A longer operating time was needed for laparoscopic surgery (1.2 hours versus 1.01 hours).

Blood Loss, Surgical↗

PubMed1998

Efficacy of transabdominal ultrasound examination in the diagnosis of early pregnancy complications in an emergency department.

OBJECTIVE: To assess the value of ultrasound in an emergency department in the diagnosis of early pregnancy complications, the efficacy of a study protocol in identifying ectopic pregnancies, and the agreement on ultrasound findings among emergency department staff and gynaecologists. METHODS: All women presenting with early pregnancy complications had a transabdominal ultrasound scan performed by the attending doctor and checked by a senior doctor. The ultrasound findings were classified as normal intrauterine pregnancy (IUP), probable abnormal pregnancy, definite ectopic pregnancy, no definite IUP, and other. Women with clinical and ultrasound findings compatible with threatened abortion were referred to a gynaecologist, or were admitted if findings suggested abnormal or ectopic pregnancy, or if a definite IUP could not be confirmed on ultrasound scan. For patients who were admitted or referred, a transvaginal ultrasound scan was performed by the attending gynaecologist. The findings of the gynaecologist were used as the gold standard. RESULTS: 151 cases were enrolled during a four month study period. Ultrasound findings in the emergency department included definite IUP in 95 (63%), probable abnormal IUP in 20 (13%), no definite IUP in 23 (21%), and other findings in four (3%). For evaluating the presence or absence of IUP, sensitivity of the initial scan was 82% (95% confidence interval 76% to 88%) and specificity 92% (88% to 96%). Agreement between junior and senior emergency department doctors on their ultrasound findings was 81% (75% to 87%) and between emergency department senior staff and gynecologists 85% (79% to 91%). The diagnoses made in the emergency department were thought to be compatible with the final assessments by gynaecologist in 72% (65% to 79%). Using either no definite IUP or other findings as a positive screening test for ectopic pregnancy, the sensitivity, specificity, positive predictive value, and negative predictive value were 80% (74% to 86%), 78% (71% to 85%), 12% (7% to 17%), and 99% (97% to 100%), respectively. CONCLUSIONS: Transabdominal ultrasound performed in the emergency department is useful in screening for early pregnancy complications. Ectopic pregnancy should be suspected when no IUP is found on preliminary scanning.

Adult↗

PubMed1998

MASH1 activates expression of the paired homeodomain transcription factor Phox2a, and couples pan-neuronal and subtype-specific components of autonomic neuronal identity.

We have investigated the genetic circuitry underlying the determination of neuronal identity, using mammalian peripheral autonomic neurons as a model system. Previously, we showed that treatment of neural crest stem cells (NCSCs) with bone morphogenetic protein-2 (BMP-2) leads to an induction of MASH1 expression and consequent autonomic neuronal differentiation. We now show that BMP2 also induces expression of the paired homeodomain transcription factor Phox2a, and the GDNF/NTN signalling receptor tyrosine kinase c-RET. Constitutive expression of MASH1 in NCSCs from a retroviral vector, in the absence of exogenous BMP2, induces expression of both Phox2a and c-RET in a large fraction of infected colonies, and also promotes morphological neuronal differentiation and expression of pan-neuronal markers. In vivo, expression of Phox2a in autonomic ganglia is strongly reduced in Mash1 -/- embryos. These loss- and gain-of-function data suggest that MASH1 positively regulates expression of Phox2a, either directly or indirectly. Constitutive expression of Phox2a, by contrast to MASH1, fails to induce expression of neuronal markers or a neuronal morphology, but does induce expression of c-RET. These data suggest that MASH1 couples expression of pan-neuronal and subtype-specific components of autonomic neuronal identity, and support the general idea that identity is established by combining subprograms involving cascades of transcription factors, which specify distinct components of neuronal phenotype.

Animals↗

PubMed1998

[Relationship of lipoprotein(a) to fibrinolytic activities in healthy subjects].

Plasma tissue-type plasminogen activator(tPA) and plasminogen activator inhibitor(PAI-1) and lipoprotein(a) [Lp(a)] in 133 healthy subjects were determined. The results demonstrated that PAI-1 activity was higher in Lp(a) > or = 0.3 g.L-1 group than Lp(a) < 0.3 g.L-1 group (P < 0.05). Univariate statistical analyses showed Lp(a) concentration was positively associated with PAI-1 activity (P < 0.01), but not with age, sex, body mass index, blood lipids or tPA activity.

Adult↗

PubMed1997

MASH1 maintains competence for BMP2-induced neuronal differentiation in post-migratory neural crest cells.

BACKGROUND: The interplay between growth factors and transcription factors in vertebrate neurogenesis is poorly understood. MASH1 is a basic helix-loop-helix (bHLH) transcription factor that is essential for autonomic neurogenesis. Bone morphogenetic protein (BMP) 2, and its relative BMP4, have been shown to induce expression of MASH1 and to promote autonomic neuronal differentiation in neural crest stem cells. The relationship between expression of MASH1 and the neurogenic competence of neural crest cells has not been investigated, however. RESULTS: We have examined the function of MASH1 in neurogenic competence using a population of immuno-isolated neural-crest-derived progenitor cells. Post-migratory neural crest cells isolated from fetal rat gut expressed Mash1, yet comprised a mixture of committed neuronal precursors and non-neuronal cells. The non-neuronal cells remained competent to differentiate to neurons, however, if challenged with BMP2. Such competence declines with time and is paralleled by a decline in Mash1 expression in the cells. Expression of endogenous Mash1 can be maintained by BMP2; in turn, constitutive expression of Mash1 from a retroviral vector maintains competence for neuronal differentiation in response to late addition of BMP2. CONCLUSIONS: These data suggest that MASH1 promotes competence for neurogenesis, in a manner similar to its homologs, the proneural genes achaete-scute in Drosophila. They also reveal an unexpected feedback interaction between BMP2 and MASH1 during neuronal differentiation. MASH1 may play multiple roles at successive stages of development within a neurogenic lineage, only one of which is revealed by a loss-of-function mutation.

Animals↗

PubMed1997

Cell lineage determination and the control of neuronal identity in the neural crest.

The molecular mechanisms underlying the determination of neuronal identity in the vertebrate peripheral nervous system are only just beginning to come into focus. Many of these mechanisms, such as the involvement of cascades of bHLH transcription factors and lateral inhibition via the Notch-Delta system, appear to have been conserved from Drosophila (Ghysen et al. 1993; Jan and Jan 1993). The way in which these genetic circuits are controlled by instructive growth factors, and the manner in which they lead to expression of a particular neuronal identity, is far from clear. This process is being elucidated by studies of neurogenesis in the peripheral autonomic lineage, which is arguably the best-understood neurogenic lineage in vertebrates. Emerging evidence is beginning to suggest that neuronal diversity within the autonomic and sensory lineages may be generated by related, but distinct, mechanisms. All autonomic progenitors express a common bHLH protein, MASH1, which appears to be induced by members of the BMP2 subfamily secreted by the tissues to which these progenitors migrate. Additional signals may then act on these progenitors in different locations to induce the expression of other transcription factors, which act in conjunction with MASH1 to specify the final phenotypes of the different autonomic neuron subtypes (sympathetic, parasympathetic, and enteric). Although different classes of autonomic neurons develop in very different locations within the body, different classes of sensory neurons are located together in dorsal root ganglia. The finding that distinct but related subtypes of bHLH proteins, the neurogenins, are expressed by different classes of sensory neuron precursors early in development suggests that sensory neuron diversity, in contrast to autonomic neuron diversity, may be pre-specified at or before the time neural crest cells begin their emigration from the neural tube.

Animals↗

PubMed1996

Identification of novel paired homeodomain protein related to C. elegans unc-4 as a potential downstream target of MASH1.

A novel paired homeodomain protein, PHD1, that is most closely related to C. elegans unc-4 has been identified by a differential RT-PCR method. PHD1 is expressed in a narrow layer adjacent to the ventricular zone of the dorsal spinal cord, immediately following expression of MASH1 but preceding overt neuronal differentiation. Some cells coexpressing MASH1 and PHD1 can be seen, suggesting that these two genes are sequentially activated within the same lineage. In the olfactory sensory epithelium, PHD1 expression not only follows but is dependent upon MASH1 function, suggesting that PHD1 acts downstream of MASH1. A sequential action of bHLH and paired homeodomain proteins is apparent in other neurogenic lineages and may be a general feature of both vertebrate and invertebate neurogenesis.

Amino Acid Sequence↗

PubMed1996

Distinct subpopulations of enteric neuronal progenitors defined by time of development, sympathoadrenal lineage markers and Mash-1-dependence.

Enteric and sympathetic neurons have previously been proposed to be lineally related. We present independent lines of evidence that suggest that enteric neurons arise from at least two lineages, only one of which expresses markers in common with sympathoadrenal cells. In the rat, sympathoadrenal markers are expressed, in the same order as in sympathetic neurons, by a subset of enteric neuronal precursors, which also transiently express tyrosine hydroxylase. If this precursor pool is eliminated in vitro by complement-mediated lysis, enteric neurons continue to develop; however, none of these are serotonergic. In the mouse, the Mash-1-/- mutation, which eliminates sympathetic neurons, also prevents the development of enteric serotonergic neurons. Other enteric neuronal populations, however, including those that contain calcitonin gene related peptide are present. Enteric tyrosine hydroxylase-containing cells co-express Mash-1 and are eliminated by the Mash-1-/- mutation, consistent with the idea that in the mouse, as in the rat, these precursors generate serotonergic neurons. Serotonergic neurons are generated early in development, while calcitonin gene related peptide-containing enteric neurons are generated much later. These data suggest that enteric neurons are derived from at least two progenitor lineages. One transiently expresses sympathoadrenal markers, is Mash-1-dependent, and generates early-born enteric neurons, some of which are serotonergic. The other is Mash-1-independent, does not express sympathoadrenal markers, and generates late-born enteric neurons, some of which contain calcitonin gene related peptide.

Animals↗

PubMed1995

Transvaginal endoscopic oophorectomy.

Four women underwent transvaginal endoscopic oophorectomy during vaginal hysterectomy. The adnexa were visualized with a laparoscope inserted into the upper vagina. Bilateral salpingo-oophorectomy or oophorectomy was carried out with standard laparoscopic instruments introduced through the vagina without a pneumoperitoneum; Endoloop sutures and bipolar electrocoagulation were used for hemostasis.

Fallopian Tubes↗

PubMed1995

Postmigratory neural crest cells expressing c-RET display restricted developmental and proliferative capacities.

c-RET is an orphan receptor tyrosine kinase essential for enteric neurogenesis in mice and is involved in several human genetic disorders. RET is also one of the earliest surface markers expressed by postmigratory neural crest cells in the gut. We generated anti-RET monoclonal antibodies to isolate such cells. We find that RET+ cells are antigenically and functionally distinct from neural crest stem cells (NCSCs) characterized previously. Unlike NCSCs, which are RET- and MASH1-, most RET+ cells express MASH1. Moreover, unlike NCSCs, which are multipotent and have high proliferative capacity, many RET+ cells generate only neurons following a limited number of divisions. This behavior is observed even in the presence of glial growth factor, a polypeptide that suppresses neuronal and promotes glial differentiation by NCSCs. These data provide direct evidence for the existence of committed neuronal progenitor cells and support a model of neural crest lineage diversification by progressive restriction of developmental potential.

Animals↗

PubMed1995

Comparative yield of endocervical and metaplastic cells. Two sampling techniques: wooden spatula and cytology brush.

OBJECTIVE: To compare two sampling techniques in their ability to obtain endocervical and metaplastic cells from the Papanicolaou smear. DESIGN: Prospective clinical trial comparing the criterion standard of a wooden spatula to a cytology brush. SETTING: Community-based family medicine clinic in London, Ont. PATIENTS: Consecutive sample of 102 women aged 15 to 58 years requiring a Pap smear between October 1992 and October 1993 who presented to the office of their family physician and were assessed by one resident or one faculty physician. INTERVENTIONS: A Pap smear was obtained from each participant using first the wooden spatula and then the cytology brush. MAIN OUTCOME MEASURES: The number of Pap smears done in the study population that contained endocervical or metaplastic cells. RESULTS: Endocervical cell yield was significantly greater using the cytology brush (93.1%) than using the spatula (61.8%) (P < 0.001). There was no significant difference in metaplastic cell yield between the cytology brush (71.6%) and the spatula (63.7%). At least one of these cell types was identified on 95.1% of cytology brush samples and on 79.4% of spatula samples (P < 0.001). The resident and faculty physician were not significantly different in their rate of detecting endocervical or metaplastic cells. CONCLUSIONS: Adding a cytology brush sample to the Pap smear resulted in a significant increase in the rate of Pap smears that detected cells. The cytology brush was significantly better than the spatula for detecting endocervical cells (P < 0.001), but not significantly better for detecting metaplastic cells.

Adolescent↗

PubMed1994

Comparison of prostaglandin E2 vaginal tablet with amniotomy and intravenous oxytocin for induction of labour.

Prostaglandins have been increasingly used in obstetrical practice for cervical ripening and induction of labour. We set out to investigate the effectiveness of prostaglandin E2 (PGE2) vaginal pessaries in inducing labour in the Chinese population in Hong Kong. In the period August, 1991 to August, 1992, we recruited 206 pregnant Chinese women who required induction of labour for various obstetrical indications into the trial. The study group had induction of labour by PGE2 vaginal pessaries and the control group underwent amniotomy plus oxytocin infusion. These patients were alternately assigned either method of induction. They were further divided into primiparous and multiparous (parity 1 and 2 only) groups. Only 101 primiparas and 99 multiparas were available in the final analysis of the trial. Various aspects of labour, delivery, maternal and fetal outcome were compared. For primiparas, the traditional combined induction was the preferred method. For multiparas, both induction methods were quite satisfactory and there was a trend toward lesser blood loss and pethidine requirement in the PGE2 users.

Adolescent↗

PubMed1994

MASH-1: a marker and a mutation for mammalian neural crest development.

The ability to generate mice containing null mutations in any cloned gene promises new insights into the molecular control of mammalian neural crest development. This approach has recently been applied to MASH-1, a transcription factor in the bHLH family that is a mammalian homologue of the Drosophila proneural genes achaete-scute. In wild-type embryos, this gene is expressed early in the development of the autonomic nervous system, in apparent precursors of sympathetic, parasympathetic, and enteric neurons (as well as in restricted regions of the central nervous system). A null mutation in the MASH-1 gene eliminates sympathetic and parasympathetic neurons and enteric neurons of the foregut (esophagus); however, enteric neurons of the stomach and hindgut are only partially affected. Analysis with other markers indicates that the mutation acts after neural crest cells have localized in the anlagen of the autonomic nervous system to prevent neuronal differentiation. The differentiation of autonomic glia appears unaffected. Thus, MASH-1 provides one of the most specific mutations affecting neural development in mammals, as well as a valuable marker to study the early segregation of neural crest cell lineages.

Adrenal Glands↗

PubMed1993

Sympathetic neuroblasts undergo a developmental switch in trophic dependence.

Sympathetic neurons require NGF for survival, but it is not known when these cells first become dependent on neurotrophic factors. We have examined in vitro mitotically active sympathetic neuroblasts immuno-isolated from different embryonic stages, and have correlated this functional data with the expression of neurotrophin receptor mRNAs in vivo. Cells from E14.5 ganglia are supported by neurotrophin-3 (NT-3) in a serum-free medium, but not by NGF; NT-3 acts as a bona fide survival factor for these cells and not simply as a mitogen. By birth, sympathetic neurons are well-supported by NGF, whereas NT-3 supports survival only weakly and at very high doses. This change in neurotrophin-responsiveness is correlated with a reciprocal switch in the expression of trkC and trkA mRNAs by sympathetic neuroblasts in vivo. These data suggest that neurotrophic factors may control neuronal number at earlier stages of development than previously anticipated. They also suggest that the acquisition of NGF-dependence may occur, at least in part, through the loss of receptors for these interim survival factors.

Animals↗

PubMed1993

The health care experience and health behaviour of the Chinese: a survey based in Hull.

Lack of knowledge about the health care experience and health behaviour of an important ethnic minority group prompted a study to inform the provision of health care and promote local action in Hull. Thirty Chinese 'takeaway' shops were randomly selected from the Yellow Pages of the Hull telephone directory, and all Chinese people working in them asked to complete a questionnaire. It contained questions on their knowledge, use and experience of primary health care and health promotion, together with aspects of their health behaviour. The same questionnaire in English was delivered to all workers in 30 fish and chip shops, to provide a White comparison group. Eighty (71 per cent) of the Chinese returned their questionnaire, and 73 (67 per cent) were returned from the chip-shop workers. The results indicate that the Chinese in Hull are not making optimal use of health services; they use some services inappropriately, whereas others, such as preventive health programmes, are under-used. One of the main reasons is identified as the language/communication difficulties faced by many Chinese. Other reasons are also highlighted and their implications discussed. The findings of this survey are in keeping with the mainly unpublished work undertaken elsewhere on this comparatively little researched ethnic minority group.

Adult↗

PubMed1990

Differential interactions of indolealkylamines with 5-hydroxytryptamine receptor subtypes.

Affinities of drugs for 21 indolealkylamine derivatives, some with putative hallucinogenic activity, were determined at 5-HT1A, 5-HT2A and 5-HT2B recognition sites, using radioligand competition studies. Nearly all of the derivatives displayed greatest potency for the 5-HT2A receptor, labelled by [125I]R-(-)DOI in the cortex of the rat. Most derivatives displayed 2-10 times lower affinity at the HT2B receptor labelled by [3H]ketanserin in bovine cortex. Derivatives lacking ring substituents displayed lower affinities for all of the recognition sites, compared to derivatives substituted in the 4- or 5-position of the indole ring. The 4-hydroxylated derivatives displayed 25-380-fold selectivity for the 5-HT2A site, vs the 5-HT1A site, while the 5-substituted derivatives displayed approximately equal potency at the 5-HT1A and 5-HT2A sites. Affinity of all the compounds at the 5-HT2B site was greater than 300 nM. The 6-substituted derivatives displayed greater than micromolar affinities for all of the 5-HT recognition sites examined. The size of the N,N-dialkyl substituent was a secondary determinant of affinity, with groups larger than N,N-diisopropyl resulting in a marked reduction in affinity at both the 5-HT2A and 5-HT1A recognition sites. This study demonstrated that hallucinogenic 4-hydroxy-indolealkylamines, like psychotomimetic phenylisopropylamines, bind potently and selectively to the 5-HT2A recognition site, labelled by [125I]R-(-)DOI. This provides further evidence indicating that this recently described subtype of the 5-HT2 receptor may partially mediate the action of hallucinogenic agents.

8-Hydroxy-2-(di-n-propylamino)tetralin↗