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Biomedical subjects

C Lai

Publications and source records attributed to C Lai.

At least 73 records · Page 4Linked to original sources

[Effect of interferon on filtering blebs after trabeculectomy in rabbit eyes].

A study on the suppressive effect of interferon on the formation of filtering surgical scar was carried out. Trabeculectomy was performed on 6 rabbit eyes. 100,000 Units of interferon were subconjunctivally injected at the filtering bleb during the operation and on the 3rd and 7th post-operative day. The filtering blebs, filtering function and the scanning electron microscopic examinations of the surgical areas of the walls of the globes were observed. The results show that interferon can reduce the scar, improve filtering function and can be tried clinically.

Animals↗

Naturally occurring variation in bristle number and DNA polymorphisms at the scabrous locus of Drosophila melanogaster.

The association between quantitative genetic variation in bristle number and molecular variation at a candidate neurogenic locus, scabrous, was examined in Drosophila melanogaster. Approximately 32 percent of the genetic variation in abdominal bristle number (21 percent for sternopleural bristle number) among 47 second chromosomes from a natural population was correlated with DNA sequence polymorphisms at this locus. Several polymorphic sites associated with large phenotypic effects occurred at intermediate frequency. Quantitative genetic variation in natural populations caused by alleles that have large effects at a few loci and that segregate at intermediate frequencies conflicts with the classical infinitesimal model of the genetic basis of quantitative variation.

Alleles↗

Genetic applications of transposable elements in eukaryotes.

Transposable elements have many potential applications in genetic research, including insertional mutagenesis, gene mapping, gene cloning, gene transfer within and between species, and identification of genes expressed in specific tissues at a particular time. All these genetic approaches are important in the study of molecular biology and evolution. As the number of known transposable element families increases and their properties are further documented, their utility as genetic research tools will become greater. The purpose of this article is to discuss the salient properties of transposable elements in eukaryotes and their applications to genetic research.

Animals↗

Structure, expression, and activity of Tyro 3, a neural adhesion-related receptor tyrosine kinase.

We have isolated mouse cDNA clones encoding Tyro 3, a receptor protein-tyrosine kinase (PTK) of the mammalin central nervous system (CNS). Expression of the Tyro 3 gene is strongly up-regulated in neurons of the mouse neocortex, cerebellum, and hippocampus after the day of birth, during periods of active synaptogenesis, and high expression is maintained in the adult CNS. The sequence of Tyro 3 cDNAs predicts a glycoprotein receptor with similarity to neural cell recognition and adhesion molecules--the extracellular (ligand binding) region of this receptor is composed of two immunoglobulin-related domains followed by two fibronectin type III repeats. Immunoblot and immunoprecipitation analyses with anti-Tyro 3 antibodies indicate that the 125 kD Tyro 3 protein is abundantly expressed in CNS synaptosomes, and immunohistochemical analysis of cultured hippocampal cells demonstrates that Tyro 3 is a product of neurons. Rat-2 fibroblasts stably transfected with a Tyro 3 expression construct acquire the ability to grow in soft agar, suggesting that Tyro 3 is potentially oncogenic.

Amino Acid Sequence↗

Structure and expression of the Tyro 10 receptor tyrosine kinase.

We have isolated cDNA clones encoding Tyro 10, a novel receptor protein-tyrosine kinase (PTK) whose catalytic domain exhibits significant similarity to the Trk family of neurotrophin receptors (Lai & Lemke, 1991). We find that the Tyro 10 gene is widely expressed, both within and outside the nervous system, and in both developing and mature neural tissue. The primary structure of Tyro 10, deduced from cDNA sequence, defines a new sub-family of receptor PTKs. Although the Tyro 10 kinase domain is more closely related to the equivalent domains of Trk, TrkB and TrkC than to the catalytic domains of other receptor PTKs, it is less closely related to these Trk domains than they are to each other. More significantly, the Tyro 10 extracellular (ligand binding) domain is not structurally related to the extracellular domains of the Trk receptors, but instead bears homology to cell surface mediators of protein-protein interactions, including blood coagulation Factors V and VIII, and the neuronal recognition protein A5. These appear to be structural features of a distinct receptor PTK sub-family, in that they are also found in the recently-described discoidin domain receptor (DDR).

Amino Acid Sequence↗

The human TYRO3 gene and pseudogene are located in chromosome 15q14-q25.

Partial cDNAs of the human TYRO3 gene, encoding a putative receptor tyrosine kinase, and its processed pseudogene (TYRO3P) were cloned from human teratocarcinoma cell, bone marrow and melanocyte cDNA libraries. The tyrosine kinase homologous domains of TYRO3 and TYRO3P were sequenced and compared with each other and with the mouse TYRO3 gene. Abundant levels of the 4.2-kb TYRO3 mRNA were detected in human brain, and lower levels in other human tissues. TYRO3 and TYRO3P were both assigned to human chromosome 15q14-q25 by analysis of DNAs from somatic cell hybrids.

Amino Acid Sequence↗

Activin induces cell death in hepatocytes in vivo and in vitro.

While studying endocrine responses to activin in female rats, we discovered that activin caused a marked reduction in liver mass. The regressed livers exhibited no gross signs of necrosis or infarction, but histopathological evaluation revealed extensive cell death in the centrilobular regions. The dying cells appeared to fragment into structures resembling apoptotic bodies. Liver mass and histological appearance were restored after cessation of activin infusion, indicating that on an organ level, this effect was reversible. To determine whether the effects observed in vivo were caused by direct actions on the liver, we then tested activin on isolated hepatocytes in serum-free medium. Under these conditions, activin caused many hepatocytes to undergo fragmentation, which was accompanied by a loss of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)-reducing activity, an index of viability. We compared the effects of activin with those of transforming growth factor-beta because activin is structurally related to transforming growth factor-beta and because transforming growth factor-beta has been shown previously to induce cell death in hepatocytes. Both proteins caused cell death of comparable magnitude, as defined by the extent of loss of MTT-reducing activity, but transforming growth factor-beta was active at one tenth of the effective activin concentrations. A neutralizing monoclonal antibody to transforming growth factor-beta blocked the response to transforming growth factor-beta but had no effect on the response to activin. Conversely, follistatin, an activin-binding protein, blocked the response to activin but not to transforming growth factor-beta. Inhibin, which antagonizes the effects of activin in many systems, had little effect on the response to activin. Activin and transforming growth factor-beta differed in their onset of action; exposure to transforming growth factor-beta for only 1 hr induced a maximal response, whereas maximal response to activin required its continuous presence for 24 hr. These results show a novel effect of activin on cell death in hepatocytes in vivo and in vitro, suggesting that activin may have a previously unrecognized role in regulating hepatic function.

Activins↗

Mapping and characterization of P-element-induced mutations at quantitative trait loci in Drosophila melanogaster.

X chromosomes derived from crosses of inbred P and M Drosophila melanogaster strains that had extreme effects on abdominal and/or sternopleural bristle number in males, were further analyzed to determine their effects in females and to map the loci at which the mutations occurred. Seven lines that had on average 3.9 fewer sternopleural bristles than wildtype in males had average homozygous sternopleural bristle effects of -2.2. The bristle effects were partially recessive, with an average degree of dominance of -0.60. Physical mapping of the sternopleural bristle effects of these lines placed them all at approximately 24.7 cM. These mutations are apparently allelic on the basis of a complementation test, and deficiency mapping indicates they occur within chromosomal bands 8A4; 8C6. In situ hybridization analysis of the sites of P element insertions of these lines suggests that mutations probably resulted from excision of P elements at 8C on the original inbred P strain chromosome. Two additional lines, NDC(19) and DP(146), had reduced numbers of sternopleural and abdominal bristles. NDC(19) males had 9.7 fewer abdominal and 8.6 fewer sternopleural bristles than wildtype. The corresponding homozygous abdominal and sternopleural bristle number effects were -5.8 and -3.8, respectively; with the abdominal bristle effect completely recessive and the sternopleural bristle effect nearly additive. DP(146) males had 6.2 fewer abdominal and 4.1 fewer sternopleural bristles than wildtype, with homozygous abdominal bristle effects of -4.3 and sternopleural bristle effects of -2.0. Abdominal bristle effects of this line were partially recessive whereas the sternopleural bristle effects were additive. Physical mapping showed effects on both bristle traits segregated jointly in these two lines, with the NDC(19) mutation closely linked to y and the DP(146) mutation 0.17 cM from it. Complementation tests and deficiency mapping also indicate the mutations in lines NDC(19) and DP(146) are at closely linked but separate loci within chromosomal bands 1B2; 1B4-6 and 1B4-6; 1B10 respectively, with some epistatic effects. In situ hybridization analysis of sites of P element insertion suggest that the NDC(19) mutation, which may be a scute allele, was probably caused by a P element insertion in the 1B region; the DP(146) mutation is also associated with an insertion at 1B.

Animals↗

Novel and known protein tyrosine kinases and their abnormal expression in human melanoma.

We have used the polymerase chain reaction and Northern blotting to identify protein tyrosine kinases that may play an important role in the process of melanoma initiation and progression. Degenerate primers from the conserved catalytic domain of tyrosine kinase genes were used to amplify and clone partial cDNA sequences from a human melanoma cell line (DX3-LT5.1) and normal human melanocytes. When the melanoma reaction products were sequenced, 13 distinct clones were found, of which one is novel to date and has provisionally been named MEK (for melanocytic kinase). Of the remaining 12 known kinases, only two, ERB-B2 and IGF1-R, have previously been reported in pigment cells. Reaction products from melanocytes included only eight of these 13 sequences. To test for quantitative differences in tyrosine kinase expression between normal and malignant cells, a panel of eight melanoma lines and normal melanocytes was analyzed by Northern blotting. Two tyrosine kinases (JTK-14/TIE and TYRO-9) were detected in some melanomas but were not found in normal melanocytes, whereas others, including MEK, appeared to be overexpressed in some malignant lines. A minority of kinases showed either no change or a reduction in the level of mRNA. Expression of tyrosine kinases varied independently, and individual lines contained various combinations of these enzymes. Our findings are consistent with an increased overall expression of these putative growth factor receptors during melanoma development.

Amino Acid Sequence↗

Human myeloperoxidase gene cDNA cloning and expression in acute leukemia.

In this study, the light chain and a part of the heavy chain cDNA segment of human myeloperoxidase (MPO) were cloned with PCR and other DNA recombination techniques from HL-60 cell. The size of the cloned cDNA was 769 bp. A segment about 600bp of the cDNA was analyzed by DNA sequencing and showed no difference from the human MPO cDNA sequences published before. The MPO cDNA was used as a probe to study the MPO gene expression in leukemic cells. The Northern blot analysis and slot blot analysis of RNA isolated from leukemic cell lines and blast cells of acute leukemia showed that MPO gene expression correlated with myeloid lineage and might be used as a marker for the subclassification of acute leukemia.

Acute Disease↗

[The effect of nifedipine in hypertensive cardiopathy. An echocardiographic and electrocardiographic study].

To assess whether antihypertensive therapy by nifedipine can reverse left ventricular (LV) hypertrophy, 15 hypertensive patients, mean age 47 years, were serially studied during 12 months of treatment with nifedipine in slow release (40-60 mg/day), by recordings of blood pressure (BP), ECG and echocardiogram. Blood pressure decreased from 161 +/- 6/104 +/- 3 mmHg to 131 +/- 3/89 +/- 1 mmHg, p < 0.001, and this fall first became statistically significant at 1 month. From the hemodynamic view point, BP decreased for a reduction in total peripheral resistance. The Sokolow-Lyon voltage decreased significantly after 6 months (from 33.5 +/- 2.7 to 28.1 +/- 2.1 mm, p < 0.01) without further changes in the subsequent months. Left ventricular mass, by echocardiography, decreased after 6 months (from 189 +/- 15 to 176 +/- 13 g/m2, p < 0.05) and further after 12 months (169 +/- 13 g/m2, p < 0.001). The reduction in LV mass was secondary to the decrease in wall thickness, particularly in posterior wall thickness. No significant changes were observed in LV fractional shortening throughout the study. Thus, nifedipine was an effective antihypertensive agent and reverted LV hypertrophy secondary to arterial hypertension without impairment of LV systolic function.

Adult↗

Effects of iron supplementation and discontinuation on serum copper, zinc, calcium, and magnesium levels in women.

The purpose of this study was: 1) to establish the prevalence of depleted iron stores, iron deficiency, and low serum levels for copper, zinc, calcium, and magnesium in a healthy female population; and 2) to examine the effects of iron supplementation and discontinuation on the serum levels of the above minerals. One hundred eleven healthy women between the ages of 18 and 40 yr reported for fasted morning blood sampling for iron, copper, zinc, calcium, and magnesium status. Forty-five subjects were either iron-deficient as defined by a hemoglobin level below 120 g.l-1 (four subjects) or iron deplete as defined by a serum ferritin value below 20 micrograms.l-1 (43 subjects). Two subjects fit both criteria. This subgroup continued with the study and were prescribed a normal therapeutic iron dose (320 mg elemental iron per day, taken as two Slow-Fe tablets.d-1 for a period of 12 wk). The subjects then discontinued the iron supplementation for a further 12 wk. The response of the various blood minerals was monitored at 6-wk intervals. Twenty-five subjects completed the full 24-wk treatment. The main conclusions to be made from this study were that: 1) For this sample population of women, iron depletion was quite common (39%), although low hemoglobin values (< 120 g.l-1) were only seen in 3.6%. No subjects fell below the criteria for low serum copper levels (< 13.3 mumol.l-1) nor low serum magnesium levels (< 0.6 mmol.l-1). Seven subjects (6.5%) fell below the criteria for low serum zinc levels (< 11.5 mumol.l-1) while two subjects (1.8%) were below the criteria for low serum calcium levels (< 2.20 mmol.l-1). 2) Therapeutic oral iron supplementation was successful in raising mean serum ferritin values from 15.9 micrograms.l-1 to 36.5 micrograms.l-1 but was not associated with decrements in serum copper or calcium levels. 3) The treatment did not significantly effect serum zinc and magnesium levels during the supplementation period, but a downward trend continued through the discontinuation phase so that at 18 and 24 wk serum zinc and magnesium levels were significantly lower than baseline. 4) Oral contraceptive use was associated with elevated serum copper and ferritin values and lowered serum magnesium levels.

Adolescent↗

Haemodialysis as a model for studying endogenous plasma DNA: oligonucleosome-like structure and clearance.

The rate of clearance of extracellular plasma DNA in man has important implications for pathogenetic mechanisms in systemic lupus erythematosus (SLE), as well as for certain other clinical states. Present knowledge of this parameter is derived exclusively from studies of injected, naked DNA in animals. Recent information indicates that the physiologic form of plasma DNA in SLE is that of oligonucleosome-like molecules rather than of naked DNA and consists of multimeric complexes of DNA bound to histone, probably arising from an apoptotic process. In order to study the rate at which these oligonucleosome-like complexes are removed from plasma and to do so in man rather than experimental animals, we exploited the observation that during haemodialysis large amounts of DNA are released, apparently within the dialysis coil, into the patient's plasma. Since this release appears to cease promptly with termination of the procedure, it offered the potential for estimating the rate of removal of such DNA from human plasma. Moreover, if that DNA, as postulated, were shown to possess an oligonucleosome-like structure resembling that found endogenously in human SLE, the relevance of such information to the human disease state would be further enhanced. The present results support the conclusion that DNA released into plasma during haemodialysis possesses such an oligonucleosome-like structure. The plasma half-life of that DNA in man was found not to exceed 4 min. The highly dynamic state thus implied for extracellular endogenous plasma DNA in man has important implications for pathogenetic mechanisms dependent on dsDNA in SLE. Moreover, individuals undergoing chronic haemodialysis, who are thereby exposed to a very large cumulative amount of such DNA, might serve as models for studying its long-term sequelae.

DNA↗

The role of the pericardium in conditioning the effects of physical training.

More work needs to be done on the extent to which the pericardium can modulate the cardiovascular response to exercise and the mechanisms whereby this modulation is brought about. Studies are needed to differentiate the effects of the pericardium on the cardiovascular exercise response, comparing trained with untrained subjects. Evidence is accumulating that exercise training in patients with heart failure improves not only the performance of exercising muscles, but also has some beneficial effects on central hemodynamics. The extent to which these beneficial effects can be attributed to conditioning the pericardium remains speculative.

Adaptation, Physiological↗

Effect of calcium antagonists on exercise tests.

The aim of this study was to investigate the anti-ischemic and antianginal activity and the duration of the new dihydropyridine calcium blocker nisoldipine (NIS) in patients with stable angina pectoris. The research was carried out on 16 patients, all male, 41-68 (mean of 58) years of age, with stable angina pectoris and fixed ischemic threshold (variations < 15%). After a 10-day washout period, patients were randomized to treatment with either 10 mg of nisoldipine or placebo (PL), twice daily for 21 days, according to a double-blind, crossover design. Patients underwent maximal symptom-limited exercise testing at 10 W/min on a bicycle ergometer, twice during the washout period, and once at the end of each treatment period, 3 and 12 h after oral administration of the drugs. In comparison with placebo, nisoldipine increased the ischemic threshold (N, 704 +/- 45 s; PL, 548 +/- 35 s; p < 0.01) and anginal threshold (N, 766 +/- 44 s; PL, 699 +/- 42 s; p < 0.01) for at least 12 h, and the ST-segment depression significantly decreased at maximal work (PL, 2.4 +/- 0.1 mm; N, 1.8 +/- 0.2 mm; p < 0.01) and at maximal common work (PL, 2.4 +/- 0.1 mm; N, 1.15 +/- 0.2 mm; p < 0.01). Similar to placebo the rate-pressure product was not significantly changed at higher submaximal effort after N, but it was significantly increased at the level of ischemic threshold, suggesting an increase in coronary blood flow to ischemic zones. Nisoldipine possesses anti-ischemic and antianginal activity lasting at least 12 h. This activity seems to be due to an increase in coronary blood flow to ischemic zones.

Adult↗

Slow-release gallopamil in patients with stable effort angina.

Gallopamil (GSR) is a new calcium-channel blocker. The anti-ischemic activity of GSR was investigated in 12 patients with stable angina of effort, with fixed ischemic threshold (variations < 15%). After a 7-day washout period, patients were randomized to receive treatment with either GSR 100 mg or placebo twice daily for 7 days. Patients underwent maximal symptom-limited exercise test, 10 W/min on a bicycle, during washout (twice) and after the end of each treatment period. Patients were studied by electrocardiogram and the cuff method for determining systolic blood pressure. After treatment with GSR, ischemic and anginal thresholds were increased for at least 12 h in comparison with placebo (ischemic threshold: GSR 663 +/- 37, placebo 571 +/- 36, p < 0.01; anginal threshold: GSR 708 +/- 32, placebo 646 +/- 38, p < 0.05). Rate-pressure product was not changed at the same levels of exercise, but it was significantly increased during exercise at ischemic threshold. In conclusion, GSR possesses an anti-ischemic and antianginal activity lasting at least 12 h. This activity seems due to an increase of coronary blood flow to ischemic areas.

Aged↗

[The effect of nifedipine on arterial pressure and exercise tolerance in hypertensive patients].

The aim of this research was to assess whether the antihypertensive therapy with nifedipine, a dihydropyridine calcium-antagonist, is able to control hypertension not only at rest but also during exercise. So, 20 male hypertensive patients, mean age 48 years, were evaluated by symptom limited bicycle exercise (10 W/min) before and after 6 and 12 months of therapy with nifedipine in a slow releasing form (40-60 mg/day). Exercise tolerance significantly increased after 12 months of antihypertensive therapy with nifedipine (from 146 +/- 5 to 153 +/- 4 W, p < 0.05). Systolic and diastolic blood pressure decreased after 6 and 12 months both at rest (from 160 +/- 6/109 +/- 9 mmHg to 132 +/- 3/91 +/- 3 and 135 +/- 4/93 +/- 1 mmHg, respectively, both p < 0.001) and during exercise (at end exercise: from 238 +/- 7/121 +/- 5 mmHg to 216 +/- 6/106 +/- 3 and 213 +/- 6/107 +/- 3 mmHg, respectively, both p < 0.001). No significant changes in heart rate were observed during antihypertensive therapy both at rest and during exercise test. In conclusion, long-term antihypertensive therapy with nifedipine was effective in the control of hypertension both at rest and during physical stress. Moreover, an improvement in effort tolerance was observed in hypertensive patients.

Adult↗