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Biomedical subjects

M L Lai

Publications and source records attributed to M L Lai.

At least 37 records · Page 2Linked to original sources
PubMed1996

Formation of morphine from codeine in Chinese subjects of different CYP2D6 genotypes.

Codeine and morphine pharmacokinetics among different CYP2D6 genotypes was compared in this study. Polymerase chain reaction tests were used to determine CYP2D6 genotypes in leukocyte deoxyribonucleic acid in 32 unrelated volunteers. Based on the genotypes, subjects were categorized into three groups: homozygous C/C188 (n = 8), heterozygous C/T188 (n = 12), and homozygous T/T188 (n = 12). Each subject was given a single oral dose of 30 mg codeine phosphate tablet after overnight fasting. Plasma concentration of codeine and 24-hour urinary morphine recovery were measured with HPLC. All three genotypes of subjects showed almost identical time profiles of plasma codeine. Urinary morphine glucuronide was hydrolyzed with beta-glucuronidase. The total recovered amount of morphine and glucuronides was 4349 +/- 646, 2564 +/- 242, and 1127 +/- 164 nmol (mean +/- SEM), respectively, for C/C188, C/T188, and T/T188 subjects (p < 0.05). The significant lower amount of urinary morphine but identical codeine plasma concentration suggested a lower partial clearance of the formation of morphine from codeine in T/T188 subjects. The results suggest a future study to assess the analgesic effect of codeine in different genotypes of CYP2D6 extensive metabolizers.

Adult↗
PubMed1995

Epithelium-derived inhibitory prostaglandins modulate human bronchial smooth muscle responses to histamine.

The role of the bronchial epithelium and inhibitory prostaglandins in the induction of histamine tachyphylaxis in human isolated bronchial smooth muscle was investigated using bronchi obtained from 14 patients who had been treated with non-steroidal anti-inflammatory drugs (NSAID) for > 2 months and from 14 untreated patients. Epithelium-intact bronchial strips from untreated patients demonstrated tachyphylaxis to histamine with the maximum response (Emax) reduced by 30 +/- 5% (P < 0.02) and the EC50 increased 1.86-fold (P < 0.02). Tachyphylaxis was not observed in epithelium-denuded strips. In epithelium-intact bronchial preparations from NSAID treated patients, the mean initial maximum tension generated in response to histamine was significantly greater than that for bronchial preparations from untreated patients (P < 0.05). In NSAID-treated patients, both epithelium-intact and denuded preparations failed to demonstrate tachyphylaxis. The generation of prostaglandin E2 and prostacyclin was assessed by radio-immunoassay using bronchi from untreated patients (n = 8). In epithelium-intact bronchial preparations, the generation of both prostaglandin E2 and prostacyclin was significantly increased by histamine exposure (P < 0.05) and was completely inhibited by indomethacin. However, the selective histamine H2 receptor antagonist, ranitidine, selectively inhibited the synthesis of prostaglandin E2 alone. Production of both prostaglandins was not altered by exposure to acetylcholine. These results suggest that prostaglandin E2 and prostacyclin are released primarily from the epithelium in response to histamine and may be specifically involved in inhibiting human bronchial smooth muscle responsiveness to this mediator. Significantly, the release of prostaglandin E2 appears to be selectively controlled by histamine H2 receptors, resident on the epithelium.

Acetylcholine↗
PubMed1995

Propranolol disposition in Chinese subjects of different CYP2D6 genotypes.

Propranolol pharmacokinetics among different genotypes of CYP2D6 was compared in this study. The Chinese (Han) population consisted of 44 healthy unrelated individuals living in southern Taiwan. Endonuclease tests based on polymerase chain reaction were used to determine C/T188 genotypes of CYP2D6 in leukocyte deoxyribonucleic acid. Based on codon 188 genotypes, subjects were categorized into three groups: homozygous C/C188 (n = 13), heterozygous C/T188 (n = 14); and homozygous T/T188 (n = 17). Each subject was given a 40 mg propranolol tablet. Blood samples were drawn before and 12 hours after propranolol administration to measure propranolol and 4-hydroxypropranolol. Three genotypes showed distinct time profiles of plasma propranolol and 4-hydroxypropranolol. The area under plasma concentration curve values (mean +/- SEM), were 322.0 +/- 40.8, 481.6 +/- 77.5, and 766.1 +/- 92.8 nmol.hr/L, respectively, for C/C188, C/T188, and T/T188 subjects (p < 0.05). The 48-hour excreted amount of 4-hydroxy-S-propranolol-O-glucuronide, but not 4-hydroxy-R-propranolol-O-glucuronide, was significantly higher for C/C188 than for T/T188 subjects (p < 0.05). This study shows a different propranolol disposition in Chinese subjects of different CYP2D6 genotypes.

Adrenergic beta-Antagonists↗
PubMed1995

GAP-43 in the spinal trigeminal and dorsal column nuclei of the newborn and adult man: immunohistochemical distribution and comparison with that of the neuropeptides SP and CGRP.

By means of immunohistochemistry the presence of the growth-associated protein GAP-43 and its codistribution with substance P (SP) and calcitonin gene-related peptide (CGRP) are studied in the human spinal trigeminal, gracile, and cuneate nuclei at perinatal and adult life stages. The results obtained show that the distribution pattern of GAP-43 in the areas examined varies with age and that the immunohistochemical detectability of the protein persists in discrete subregions of the trigeminal and cuneate nuclei of the adult, where its localization closely matches that of SP and CGRP. It is suggested that neuronal plasticity may be pronounced throughout life in areas of the human nervous system involved in the neurotransmission of protopathic stimuli at the first synaptic level. Discrete subregions of the cuneate nucleus, bearing neurochemical characteristics strikingly similar to those of the substantia gelatinosa of the trigeminal subnucleus caudalis are pointed out.

Adult↗
PubMed1995

Population genetic study of selected tetranucleotide repeat DNA polymorphisms on chromosomes Y and 12.

Microsatellite polymorphisms of 75 unrelated Taiwanese males were analyzed for (GATA) repeats in DYS19 on chromosome Y and tetranucleotide simple repeats in D12S67 on chromosome 12. A simple nonisotopic technique based on polymerase chain reaction electrophoresis on native polyacrylamide gels followed by silver staining was used. In the 75 unrelated males, four alleles on DYS19 and five alleles on D12S67 were detected. Different allele frequencies, heterozygosity rates and information on the nature of the repeat loci were determined in these unrelated individuals. The resulting polymorphisms are of great assistance in ethnologic studies, forensic investigation and deficiency cases in paternity testing.

Base Sequence↗
PubMed1995

Magnetic resonance spectroscopic findings in patients with subcortical ischemic stroke.

BACKGROUND: Biochemical changes inside the brain during acute ictus have been extensively studied by means of magnetic resonance spectroscopy (MRS). Previous reports revealed that cerebral cortical infarction causes reduction of N-acetylaspartate (NAA) and elevation of lactate. This study was designed to evaluate the biochemical changes in subcortical infarction. METHODS: Nine normal controls and four patients, including two thalamic infarct, one basal ganglia infarct, and one putamen infarct cases were examined using MRS in addition to magnetic resonance imaging (MRI). Evaluation experiments were performed on a Siemens Wagnetom 63SP machine. A spin echo sequence with TE 270 msec was applied for the measurement. The voxel was located at basal ganglia in the controls and at the lesion site, as well as at the contralateral corresponding region in the patients. RESULTS: Three resonance signals were present in the spectrum-NAA, choline-containing compounds (Cho) and creatine-phosphocreatine (Cr). The NAA/Cho and NAA/Cr ratios were reduced significantly on the lesion side compared with the controls. NAA/Cho also decreased on the lesion side compared with the healthy side. CONCLUSIONS: There is a remarkable reduction of NAA concentration even in subcortical infarction. Further study is needed for the detection of changes in lactate in patients with subcortical lesion.

Adult↗
PubMed1995

[Cerebrovascular emergencies: difficulties and errors in diagnosing various stroke types].

The frequency of and reasons for errors in diagnosing various types of cerebrovascular disease at the emergency room of National Cheng Kung University Hospital were analyzed in 548 consecutive patients from January to December 1990. Each patient was evaluated by neurological residents and a bedside diagnosis was made on the basis of history-taking, physical examination, and diagnostic reasoning. The emergency diagnosis was made after finishing the radiological and/or laboratory investigations. The tentative emergency diagnosis of each patient was judged as correct or not by comparison with the final diagnosis, which was based on either the results of specific investigation or on the typical cerebrovascular syndrome ascertained by the attending physicians if the specific investigation was not helpful. If the tentative emergency diagnosis had been judged to be wrong, the cause for the misdiagnosis was determined by reviewing the records of the entire diagnostic process. The diagnosis in the emergency setting was erroneous in 131 (24%) patients. Primary intraventricular hemorrhage, cerebral venous thrombosis and subarachnoid hemorrhage were frequently misdiagnosed as compared with other types of stroke. The explored reasons for diagnostic inaccuracy were: inadequate basic data (46%), reasoning errors (38%), and lack of fundamental knowledge (16%). These results implied that the education and training for diagnosis of subarachnoid hemorrhage in emergency should be enhanced. Deeply comatose states caused diagnostic difficulties in data collection. Diagnostic errors were frequently encountered in unusual stroke or stroke with atypical presentations. To increase diagnostic ability in cerebrovascular emergencies, residents should strive to improve interview and examination skills and reasoning discipline. Modern technology is not a panacea for diagnostic difficulties.(ABSTRACT TRUNCATED AT 250 WORDS)

Cerebrovascular Disorders↗
PubMed1994

GAP-43 persists in adulthood and coexists with SP and CGRP in human trigeminal sensory neurones.

Immunohistochemistry was used to examine the occurrence and colocalization of the growth-associated protein GAP-43 with substance P (SP) and calcitonin gene-related peptide (CGRP) in the human trigeminal ganglion and sensory nucleus at perinatal and adult life stages. The results obtained show that: GAP-43-like immunoreactive (LI) material persists in trigeminal primary sensory neurones of the normal adult; the GAP-43-LI ganglionic population partially overlaps with those immunoreactive to SP and CGRP; the distribution pattern of the protein in the spinal nucleus varies with age; in the adult subnucleus caudalis GAP-43 is co-distributed with SP and CGRP. It is suggested that the trigeminal GAP-43-LI neuronal system may retain the capacity for structural and functional plasticity in adult life.

Adult↗
PubMed1994

Purification and biochemical characterization of a recombinant mouse seminal vesicle trypsin inhibitor produced in Escherichia coli.

Escherichia coli cells were transformed with an expression vector constructed by inserting a DNA fragment encoding a Kazal-type trypsin inhibitor from mouse seminal vesicle into pGEX-2. The cloned cells were able to produce a high yield of a chimeric polypeptide made by fusing the trypsin inhibitor to glutathione S-transferase. The chimeric polypeptide could be purified through an affinity column of glutathione agarose beads. The purified protein could be digested with thrombin to release the recombinant trypsin inhibitor which could be further purified by HPLC of the thrombin digests on a reverse-phase C4 column. The recombinant trypsin inhibitor was homogeneous and showed trypsin inhibitor activity as strong as that of the naturally occurring trypsin inhibitor.

Amino Acid Sequence↗
PubMed1993

Dual effect of valproic acid on the pharmacokinetics of phenytoin.

To evaluate the effects of valproic acid on the disposition of phenytoin, a single dose of 600 mg valproic acid and multiple doses of valproic acid (200 mg four times a day for 5 days) were administered together with a single oral dose of 600 mg phenytoin to 12 young male volunteers. Fraction of unbound phenytoin and the area under curve (AUC) of the total and unbound phenytoin in plasma were compared with the control phase in which only 600 mg phenytoin was given. Valproic acid increased the unbound fraction of phenytoin in both single- and multiple-dose studies by 15 per cent and 41 per cent, respectively. Single-dose valproic acid increased the total AUC of phenytoin by 11 per cent. Multiple-dose valproic acid decreased the total AUC by 7 per cent. Single- and multiple-dose valproic acid increased the unbound AUC by 25 per cent and 18 per cent, respectively, probably due to the inhibition on the metabolizing enzymes. We concluded that there are at least two mechanisms involved in valproic acid-phenytoin interaction. Whereas valproic acid displacing phenytoin on the plasma protein decreased the total drug concentration of phenytoin, the enzyme inhibition by valproic acid increased both the total and unbound concentration of phenytoin. The two conflicting mechanisms may result in different effects on the total plasma concentration of phenytoin. Therapeutic drug monitoring based on the total concentration of phenytoin may be misleading when valproic acid is co-administered.

Administration, Oral↗
PubMed1993

Molecular basis of genetic variation in debrisoquin hydroxylation in Chinese subjects: polymorphism in RFLP and DNA sequence of CYP2D6.

Debrisoquin hydroxylation phenotype was determined in 124 Chinese persons living in Taiwan, and two poor metabolizers were identified with a urinary metabolic ratio (MR) greater than 12.6. The other subjects, extensive metabolizers, showed a normal frequency distribution of log(MR). Most subjects (50%) showed a 44/29 kb pattern in restriction fragment length polymorphism (RFLP) analysis with use of Xba I, and 30% and 15% of the subjects exhibited a homozygous 29/29 kb and 44/44 kb pattern, respectively. Among extensive metabolizers, subjects with the 44/44 kb pattern had a significant higher log(MR) than those with the 44/29 pattern, and the log(MR) of the subjects with the 44/29 kb pattern was significantly higher than that of the subjects with 29/29 kb pattern. All nine exons and intron 3 of C gamma P2D6 were amplified with polymerase chain reaction (PCR) and sequenced for four extensive metabolizers. Two major polymorphisms were found: one at position 188 of exon 1 and the other at position 4268 in exon 9. With PCR and endonuclease digestion, polymorphisms at exon 1, intron 3, and exon 9 were investigated. Only two of 254 alleles showed a heterozygous guanine at 1934 base pairs (G1934) to adenine (A) mutation, commonly found in white poor metabolizers. Approximately 70% of alleles showed thymine at 188 base pairs (T188), and 76% showed cytosine at 4268 base pairs (C4268) instead of C188 and G4268, as is found in most white subjects. Subjects with T188 or C4268 showed a significant higher log(MR) than subjects with homozygous C188 and G4268. The C/T188, G/A1934, G/C4268, and RFLP polymorphisms may explain the interracial variations between Chinese and white subjects, as well as the genetic variations among Chinese subjects.

Adult↗
PubMed1993

Effects of fish oil supplementation on acute ischemic brain injury in the rat.

We studied the effects of long-term fish oil (FO) dietary supplementation on brain edema, polymorphonuclear neutrophil (PMN) infiltration, and infarct size in a rat stroke model. Rats were given regular rat chow with or without FO supplement (20% of total calories) for 7 weeks. Body weight did not differ between the two groups. In the FO group, an increase in eicosapentaenoic acid and a decrease in arachidonic acid content in hepatic phospholipids were significant in the phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine but not in the phosphoinositol fraction. Platelet activity reflected by serum thromboxane B2 levels was reduced in the FO group. Postischemic brain edema and PMN infiltration were not different between the two groups. The infarct volume was significantly greater in the FO group (controls: 96 +/- 7 mm3, n = 49; FO group: 124 +/- 6 mm3, n = 53; p = 0.0036). The greater ischemic brain injury in the FO-supplemented animals is probably related to the intraischemic hyperglycemia, which was worse in the FO group than in the control group (controls: 265 +/- 19 mg/dl, n = 14; FO group: 340 +/- 18 mg/dl, n = 16; p = 0.0079).

Animals↗
PubMed1993

Nuclear proteins of the bovine esophageal epithelium. I. Monoclonal antibody W2 specifically reacts with condensed nuclei of differentiated superficial cells.

Cells from three layers of the bovine esophageal epithelium, representing different stages of differentiation, were dissociated and separated by Percoll gradient centrifugation into fractions of small, medium and large sizes. A majority of the large cells possessed condensed nuclei, a characteristic feature of terminal differentiation of the superficial epithelium. The small cells resembled the proliferate cells of the basal layer. In vitro culture of the esophageal epithelial cells resulted in proliferation of the small cells, colony formation, and, in some cases, differentiation into cells with condensed nuclei. Nuclei, or nuclear subfractions derived from cells of the different layers, were used as immunogens for the generation of hybridomas secreting monoclonal antibodies that bound specifically to different regions of the esophageal tissue. One such antibody, designated W2, labeled the condensed nuclei from the superficial layer of stratified esophageal and corneal epithelia in situ, as well as the large cells from esophageal culture in vitro. Thus, the expression of the W2 antigen may be associated with the process of nuclear condensation during epithelial differentiation. Immunoisolation of the target antigen of W2 from extracts of large cells of the bovine esophagus yielded a band of M(r) approximately 33,000 on nonreducing polyacrylamide gels. This band dissociated into two polypeptides, of M(r) approximately 22,000 and approximately 11,000, upon treatment with dithiothreitol. Amino acid sequence analysis of the larger polypeptide showed extensive homology to a group of small calcium-binding proteins, including two helix-turn-helix motifs designated as the EF-hand, characteristic of the configuration of the metal-ion coordinating ligands of the calcium-binding site. Similarly, the sequence at the amino terminus of the polypeptide of approximately 11,000 indicated that it was the light chain counterpart of the same calcium-binding protein complex.

Amino Acid Sequence↗
PubMed1993

The effects of putaminal hemorrhage upon motoneuron excitability.

To evaluate the putaminal influence on spinal motoneuron excitability, H-reflex recovery curve (HRRC) was studied in 24 patients with putaminal hemorrhage. Thirteen patients had increased facilitation, most significantly between 150 msec and 300 msec after the conditioning stimulus. It is proposed that putaminal dysfunction may cause an impairment in inhibition of soleus motoneuron excitability. Such a putaminal disinhibition is probably related to a disturbance of the thalamo-striatal and thalamic fasciculus circuits.

Adult↗