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Biomedical subjects

C Lai

Publications and source records attributed to C Lai.

At least 55 records · Page 3Linked to original sources
PubMed1997

Neuregulin-2, a new ligand of ErbB3/ErbB4-receptor tyrosine kinases.

The neuregulins (NRGs) are a family of multipotent epidermal-growth-factor-like (EGF-like) factors that arise from splice variants of a single gene. They influence the growth, differentiation, survival and fate of several cell types. We have now discovered a set of new neuregulin-like growth factors, which we call neuregulin-2 (NRG-2): these are encoded by their own gene and exhibit a distinct expression pattern in adult brain and developing heart. Like NRG-1, the EGF-like domain of the new ligands binds to both the ErbB3- and ErbB4-receptor tyrosine kinases. However, NRG-2 stimulates different ErbB-receptor tyrosine-phosphorylation profiles from NRG-1. Our results indicate that NRG-1 and NRG-2 mediate distinct biological processes by acting at different sites in tissues and eliciting different biochemical responses in cells.

Amino Acid Sequence↗
PubMed1997

Non-promoting effects of iron from beef in the rat colon carcinogenesis model.

Significant alarm has existed among the general public in the past few years that eating red meat may cause human colon cancer. Iron in beef has been hypothesized as one of the factors in the etiology of this cancer. The present study was designed to test the hypothesis that dietary iron solely from beef would enhance colon tumorigenesis induced in rats. Tumors were induced in Sprague-Dawley rats with 1,2-dimethylhydrazine (20 mg/kg body weight for 10 weeks). Seventy male weanling rats were randomized to two dietary treatment groups with two iron sources (very lean beef vs. iron citrate) as the factor. The rats were allowed free access to the respective diet and deionized water for 27 weeks. At termination of the study, the rats were examined for location, size and type of colon or extracolonic lesions. No significant differences were found in total incidence and number of colon tumors between the beef (51.7%, 0.8 tumors/rat) and casein (62.1%, 0.9 tumors/rat) diets, although the serum iron levels of rats fed the beef diet were higher than for those fed the casein diet. The results demonstrate that, when lean beef is used as an iron source, the risk for colon carcinogenesis is not increased.

Adenocarcinoma↗
PubMed1997

Event-related potentials associated with judgment: comparison of S1- and S2-choice conditions in a contingent negative variation (CNV) paradigm.

To elucidate the functional role of association cortex in judgment and decision-making about external stimuli, the scalp topography of contingent negative variation (CNV) recorded in 9 normal volunteers was compared in two settings; dichotomous S1- and S2-choice paradigms using right wrist extension or flexion movement upon S2 as the choice reaction task with an S1-S2 interstimulus interval of 2 s. Two main findings were obtained. First, early CNV in the S1-choice paradigm consisted of a frontal to frontopolar midline negative potential, most likely representing judgment more than orienting response, and a left-sided parietal positive potential, at least partially representing P3b, whereas in the S2-choice paradigm it consisted only of a smaller frontal negative potential shift, most likely representing merely an orienting response. This suggests that the prefrontal and left parietal association cortexes might be active in the judgment and decision-making process. Second, after S2, two positive peaks (334 and 545 ms after S2) were observed at the midline central to left parietal areas only in the S2-choice paradigm. In the S1-choice paradigm, one large negative peak (275 ms after S2) was observed. We postulate that the first peak of the S2-choice paradigm is related to decision making or judgment and that the second peak is related to the following cognitive process. We conclude that at least the prefrontal and parietal association cortexes generate transient potentials accompanying judgment, and possibly decision making.

Adult↗
PubMed1997

Worldwide variations in prevalence of symptoms of allergic rhinoconjunctivitis in children: the International Study of Asthma and Allergies in Childhood (ISAAC).

BACKGROUND: As part of the International Study of Asthma and Allergies in Childhood (ISAAC), prevalence surveys were conducted among representative samples of school children from locations in Europe, Asia, Africa, Australia, North and South America. SUBJECTS: 257,800 children aged 6-7 years from 91 centres in 38 countries, and 463,801 children aged 13-14 years from 155 centres in 56 countries. METHODS: Written symptom questionnaires were translated from English into the local language for self-completion by the 13-14-year-olds and completion by the parents of the 6-7-year-olds. Rhinitis was described as a problem with sneezing, or a runny, or blocked nose when you (your child) DID NOT have a cold or the flu. Additional questions were asked about rhinitis associated with itchy-watery eyes, interference with activities and a history of hay fever ever. RESULTS: The prevalence of rhinitis with itchy-watery eyes ("rhinoconjunctivitis") in the past year varied across centres from 0.8% to 14.9% in the 6-7-year-olds and from 1.4% to 39.7% in the 13-14-year-olds. Within each age group, the global pattern was broadly consistent across each of the symptom categories. In centres of higher prevalence there was great variability in the proportion of rhinoconjunctivitis labelled as hay fever. The lowest prevalences of rhinoconjunctivitis were found in parts of eastern Europe, south and central Asia. High prevalences were reported from centres in several regions. CONCLUSION: These results suggest substantial worldwide variations in the prevalence and labelling of symptoms of allergic rhinoconjunctivitis which require further study. These differences, if real, may offer important clues to environmental influences on allergy.

Adolescent↗
PubMed1997

Prevalence of sleep-disordered breathing in diastolic heart failure.

OBJECTIVE: Sleep-disordered breathing (SDB) is common in congestive heart failure. While isolated diastolic heart failure (DHF) accounts for up to a third of all cases of congestive heart failure, the prevalence of SDB in DHF is unknown. We aim to determine the prevalence and characteristics of SDB in a group of patients with symptomatic DHF. METHODS: Twenty subjects with symptomatic DHF (New York Heart Association class II or III) and isolated diastolic dysfunction on echocardiography were assessed with lung function tests, modified sleep and health questionnaire, and overnight polysomnography. Significant SDB was defined as an apnea/hypopnea index (AHI) > 10. RESULTS: Thirteen female and seven male subjects (mean age, 65+/-6.0 years; mean body mass index (BMI), 28+/-3.2) were evaluated, of whom 17 (85%) had a diagnosis of hypertension. Overall sleep quality was poor, with fragmentation and frequent arousals associated with respiratory events. Fifty-five percent of the patients had significant SDB, mainly obstructive apneas. BMI and the prevalence of hypertension were similar in patients with and without SDB. The deceleration time, an index of diastolic dysfunction, was more prolonged in the group with SDB (236+/-40 ms vs 282+/-31 ms; p<0.05). As a group, a lower minimum percentage arterial oxygen saturation during sleep, but not the AHI was associated with more severe degree of diastolic dysfunction on echocardiogram, including a lower ratio between the early peak transmittal flow velocity and the late peak atrial systolic velocity (rho=0.57; p<0.05) and a prolonged isovolumic relaxation time (rho=-0.54; p<0.05). CONCLUSIONS: SDB is common in patients with DHF. Patients with DHF and SDB may be associated with worse diastolic dysfunction than those without SDB, although a causal relationship remains to be established.

Aged↗
PubMed1997

[Transfer and expression of rh-SCF gene in human hematopoietic stem/progenitor cells].

OBJECTIVE: To explore the transfer and expression of recombinant human stem cell factor (rh-SCF) gene in human hematopoietic stem/progenitor cell. METHODS: pLXSN-SCF, a recombinant retrovirus vector of soluble human SCF gene, was constructed by recombinant gene technique. The recombinant plasmid was introduced into virus packaging cells psi2 and PA317 by lipofectin-mediated DNA transfection, and PA317/SCF, the recombinant virus producing cell, was obtained by G418 screening [the virus potency was (2.4-8.5) x 10(5) CFU/ml]. Then, human hematopoietic stem/progenitor cells were transfected with PA317/SCF. The transfer and expression of human SCF gene were assayed by PCR, APAAP immunohistochemical staining and chemoluminance-direct ELISA. RESULTS AND CONCLUSION: retrovirus-mediated rh-SCF gene was successfully transferred and expressed in human hematopoietic stem/progenitor cells.

Animals↗
PubMed1997

[The role of MPO mRNA, IgH mRNA and CD3epsilon mRNA expressions in classification of acute leukemias].

OBJECTIVE: To compare the role of genotypic and immunophenotypic markers in classification of acute leukemia. METHODS: Expression of myeloperoxidase (MPO), CD3epsilon chain and immunoglobulin heavy chain (IgH) gene in 69 cases of acute leukemia were studied by in situ hybridization with streptavidin-gold (ISH-SAG). RESULTS AND CONCLUSION: MPO mRNA and CD3epsilon mRNA expressions were specific for early diagnosis of AML and T-ALL, respectively; and IgH mRNA expression did for early B cell leukemia. Combination of genotypic and immunophenotypic markers assured accurate lineage diagnosis of leukemias.

CD3 Complex↗
PubMed1997

Two cases of chlorinated hydrocarbon-associated myocardial ischemia.

Chlorinated hydrocarbons are well known to produce ventricular arrhythmias because of myocardial sensitization to endogenous catecholamines, but cases of myocardial ischemia have not been described frequently. We report 2 cases of myocardial ischemia after exposure to chlorinated hydrocarbons. The first patient developed an asymptomatic myocardial infarction after inhalation of 1,1,1-trichloroethane at work. It is believed that 1,1,1-trichloroethane produced a coronary spasm that was sufficient to cause myocardial necrosis in the presence of coronary vessels already compromised by atherosclerosis. The second patient developed a reversible symptomatic myocardial ischemia of 4 h duration after chloral hydrate overdose. The evolution in both patients was favorable. Exposure to chlorinated hydrocarbons can be associated with myocardial ischemia particularly if the coronary circulation is already compromised.

Adult↗
PubMed1996

Expression of the Tyro4/Mek4/Cek4 gene specifically marks a subset of embryonic motor neurons and their muscle targets.

Tyro4 is a member of the eph family of receptor protein-tyrosine kinases. We present sequence analysis that identifies Tyro4 as the rat homolog of mouse Mek4 and chick Cek4. We also present expression studies that demonstrate an evolutionarily conserved pattern of expression for Tyro4, Mek4, and Cek4. Most strikingly, we find this receptor to be specifically expressed, in all three species, in a subset of motor neurons in the medial motor column and in a subset of axial, but not limb, muscles. Mek4 has previously been ascribed a role in guiding retinal axons to their targets in the optic tectum. Our results extend the purported role of Mek4 in axon guidance to include motor neurons of the medial motor column.

Amino Acid Sequence↗
PubMed1996

Ferrous iron uptake but not transfer is down-regulated in Caco-2 cells grown in high iron serum-free medium.

Caco-2 cells in culture provide an attractive model for the study of human iron absorption. Because iron status has a marked effect on human iron absorption, we devised serum-free growth conditions that allow manipulation of Caco-2 cell iron stores while maintaining growth. Caco-2 cells were cultured in serum-free media containing 0-20 micromol/L added iron. Intracellular ferritin, measured by radioimmunoassay, increased 100-fold with the addition of 20 micromol/L iron to the serum-free growth medium. Iron uptake and transfer across Caco-2 cell monolayers were measured from balanced salt solutions of ferrous and ferric forms of iron. Uptake from ferrous, but not ferric, iron was inversely related to cell ferritin concentration and culture medium iron concentration. Kinetic analysis of uptake data from solutions of ferrous and ferric iron revealed saturable and nonsaturable components for ferrous iron, but only a nonsaturable component for ferric iron. Uptake by the nonsaturable pathway was not affected by cell ferritin concentration for either form of iron. Maximal uptake from a ferrous iron solution via the saturable pathway was nearly 100% greater in cells cultured under low compared with high iron conditions. Iron transfer across Caco-2 monolayers was not proportional to iron uptake, but was related to monolayer permeability. Iron uptake by Caco-2 cells was a reliable indicator of relative iron availability. We observed no difference in iron transfer that was related to the iron status of the cell monolayer. The lack of this effect suggests that this model may be inadequate for studies of iron transfer.

Caco-2 Cells↗
PubMed1996

Characterization of the functional properties of env genes from long-term survivors of human immunodeficiency virus type 1 infection.

A small number of persons infected with human immunodeficiency virus type 1 (HIV-1) remain clinically and immunologically healthy for more than a decade after infection. Recent reports suggest that these individuals may be infected with an attenuated strain of HIV-1; however, a common genetic basis for viral attenuation has not been found in all cases. In the present study, we examined the functional properties of the HIV-1 env genes from six long-term survivors. env clones were generated by PCR amplification of proviral env sequences, followed by cloning of the amplified regions into expression vectors. Eight to ten clones from each subject were screened by transient transfection for expression of the envelope precursor glycoprotein, gp160. Those clones expressing gp160 were then cotransfected with an HIV-1 luciferase reporter vector, pNL4-3Env(-)LUC(+) and evaluated for their ability to mediate infection of phytohemagglutinin-activated peripheral blood mononuclear cells in single-cycle infectivity assays. Clones expressing gp160 were identified for all six long-term survivors, indicating the presence of proviral env genes with intact open reading frames. For two subjects, D and DH, the encoded envelope glycoproteins yielded high levels of luciferase activity when pseudotyped onto HIV-1 virions and tested in single-cycle infectivity assays. In contrast, envelope glycoproteins cloned from four other long-term survivors were poorly processed and failed to mediate infection. Sequencing of the gp120/41 cleavage site and conserved gp41 cysteine residues of these clones did not reveal any obvious mutations to explain the functional defects. The functional activity of env clones from long-term survivors D and DH was comparable to that seen with several primary HIV-1 env genes cloned from individuals with disease progression and AIDS. These results suggest that the long-term survival of subjects D and DH is not associated with overt functional defects in env; however, functional abnormalities in env may contribute to maintaining a long-term asymptomatic state in the other four cases we studied.

Cohort Studies↗
PubMed1995

Neuregulin receptors, erbB3 and erbB4, are localized at neuromuscular synapses.

Neuregulin (NRG) is concentrated at synaptic sites and stimulates expression of acetylcholine receptor (AChR) genes in muscle cells grown in cell culture. These results raise the possibility that NRG is a synaptic signal that activates AChR gene expression in synaptic nuclei. Stimulation of NRG receptors, erbB3 and erbB4 initiates oligomerization between these receptors or between these receptors and other members of the epidermal growth factor (EGF) receptor family, resulting in stimulation of their associated tyrosine kinase activities. To determine which erbBs might mediate synapse-specific gene expression, we used antibodies against each erbB to study their expression in rodent skeletal muscle by immunohistochemistry. We show that erbB2, erbB3 and erbB4 are concentrated at synaptic sites in adult skeletal muscle. ErbB3 and erbB4 remain concentrated at synaptic sites following denervation, indicating that erbB3 and erbB4 are expressed in the postsynaptic membrane. In addition, we show that expression of NRG and erbBs, like AChR gene expression, increases at synaptic sites during postnatal development. The localization of erbB3 and erbB4 at synaptic sites is consistent with the idea that a NRG-stimulated signaling pathway is important for synapse-specific gene expression.

Animals↗
PubMed1995

Aberrant neural and cardiac development in mice lacking the ErbB4 neuregulin receptor.

Various in vitro studies have suggested that ErbB4 (HER4) is a receptor for the neuregulins, a family of closely related proteins implicated as regulators of neural and muscle development, and of the differentiation and oncogenic transformation of mammary epithelia. Here we demonstrate that ErbB4 is an essential in vivo regulator of both cardiac muscle differentiation and axon guidance in the central nervous system (CNS). Mice lacking ErbB4 die during mid-embryogenesis from the aborted development of myocardial trabeculae in the heart ventricle. They also display striking alterations in innervation of the hindbrain in the CNS that are consistent with the restricted expression of the ErbB4 gene in rhombomeres 3 and 5. Similarities in the cardiac phenotype of ErbB4 and neuregulin gene mutants suggest that ErbB4 functions as a neuregulin receptor in the heart; however, differences in the hindbrain phenotypes of these mutants are consistent with the action of a new ErbB4 ligand in the CNS.

Animals↗
PubMed1995

Nitroglycerin-induced penile erection and yawning in male rats: mechanism of action in the brain.

The effect of the central administration of nitroglycerin, a potent organic nitrate vasodilator, on penile erection and yawning was studied in male rats. When given intracerebroventricularly (ICV), nitroglycerin (33-99 micrograms) induced the above responses dose-dependently. The minimal effective dose was 33 micrograms, which was active in 60% of the rats. Nitroglycerin (1.65-6.6 micrograms) induced penile erection and yawning also when injected in the paraventricular nucleus of the hypothalamus. Nitroglycerin responses were prevented by methylene blue (200-400 micrograms ICV), by d(CH2)5Tyr(Me)2-Orn8-vasotocin (0.5-1 micrograms ICV) but not hemoglobin (100-200 micrograms ICV). In contrast methylene blue (10-20 micrograms), d(CH2)5Tyr(Me)2-Orn8-vasotocin (0.05-0.1 microgram) and hemoglobin (10-20 micrograms) were ineffective when injected in the paraventricular nucleus. Systemic haloperidol (0.5-1 mg/kg IP) was also ineffective. The results suggest that nitroglycerin induces penile erection and yawning by activating brain oxytocinergic transmission through the formation of nitric oxide in the paraventricular nucleus of the hypothalamus.

Animals↗
PubMed1995

Intracranial haemorrhage during exercise testing.

We describe the occurrence of an intraparenchymal (thalamic) haemorrhage during a stress test in a hypertensive 52-year-old man who had suffered from myocardial infarction 3 months earlier. Common causes of spontaneous haemorrhage, such as arteriovenous malformation, aneurysms, neoplasm, bleeding disorders or vasculitis were excluded. This single neurological complication was observed from among 8000 exercise tests performed in our Institute from 1987 to 1993.

Cerebral Angiography↗