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Biomedical subjects

S K Lin

Publications and source records attributed to S K Lin.

At least 37 records · Page 2Linked to original sources

Expression and mutagenesis studies of cobrotoxin from Taiwan cobra.

The cDNA encoding cobrotoxin was constructed from the cellular RNA isolated from the venom glands of Naja naja atra (Taiwan cobra). The cDNA was subcloned into the expression vector pET20b(+) and transformed into BL21(DE3) Escherichia coli strain. Expressed cobrotoxin was isolated from inclusion bodies of E. coli and subjected to refolding into its folded structure. The refolded cobrotoxin was purified by high-performance liquid chromatography and exhibited a neurotoxicity in inhibiting acetylcholine-induced muscle contractions. Recombinant cobrotoxin showed a tendency to isomerize its disulfide bonds as that observed with native cobrotoxin. An appreciable decrease in the rate of isomerization reaction was observed when Glu-38 was replaced with Gln-38 or Lys-47 was replaced with Glu-47 or Gln-47. These results reflect that the element in controlling the disulfide isomerization of cobrotoxin is closely associated with the charged side chains in the cobrotoxin molecule.

Acetylcholine↗

Effects of gender and age on plasma levels of clozapine and its metabolites: analyzed by critical statistics.

BACKGROUND: Previous reports concerning the effects of gender and age on steady-state plasma concentrations of clozapine and its major metabolites, norclozapine and clozapine-N-oxide, have been controversial. Since the frequency distribution of the plasma levels is asymmetrical and skewed to the right, the statistical methods (such as analysis of variance and regression analysis) used earlier are actually inappropriate for analyzing the effects of the variables on the concentrations and might contribute to the inconsistent results. The goal of the present study, with befitting statistics, is to measure the potential effect of dose, gender, age, and body weight on plasma levels of clozapine and its 2 major metabolites. METHOD: We retrospectively analyzed data from a therapeutic drug monitoring study for steady-state plasma clozapine, norclozapine, and clozapine-N-oxide levels that was conducted in a large group of Chinese schizophrenic inpatients (male:female ratio = 83:79; age range, 33.8 +/- 9.3 years). The daily doses of clozapine had ranged from 100 to 900 mg, with a mean +/- SD value of 379.5 +/- 142.2 mg. Plasma concentrations had been measured using high-performance liquid chromatography with ultraviolet detection. Multiple linear regression was adopted to quantify the effects of various factors on the plasma levels. The natural logarithm of the plasma level was used as the dependent variable to overcome the skewness problem. RESULTS: After adjusting the effects of gender, age, and body weight by multiple linear regression, each 1-mg increment in the daily dose could raise the clozapine level by 0.31%, norclozapine by 0.27%, and clozapine-N-oxide by 0.16%. Female patients had 34.9% higher clozapine levels and 36.3% higher norclozapine, with other variables being controlled. No sex differences were demonstrated for clozapine-N-oxide levels. Each 1-year increment in age would elevate the clozapine level by 1.1%, norclozapine by 1.0%, and clozapine-N-oxide by 1.0%. Body weight could not influence the levels of these compounds. CONCLUSION: The present results suggest that women possess higher plasma levels (about one third higher) of clozapine and norclozapine, but not the N-oxide metabolite. Each addition of 1 year in age elevated clozapine and either metabolite's levels by about 1%. Furthermore, every 1-mg increase in the daily dose raised clozapine and norclozapine concentrations by approximately 0.3%. These findings could assist clinicians in optimizing clozapine dosing strategies.

Adult↗

Term pregnancy in a noncommunicating rudimentary horn of an unicornuate uterus: a case report.

A case of full-term pregnancy in the noncommunicating rudimentary horn of unicornuate uterus is presented. A healthy female infant weighing 2,985 g was delivered by cesarean section at 37 weeks' gestation. The diagnosis was missed by prenatal ultrasonography and was made only at laparotomy. A retrospective analysis of our ultrasound studies revealed that the echo pattern of the nongravid uterus resembled a soft pelvic mass. Color Doppler imaging revealed prominent low-impedance uterine arcuate-radial arterial blood flow surrounding the periphery of the pelvic mass, as well as multiple areas of placental implantation with a pulsatile lacunar flow pattern. A high index of suspicion of rudimentary horn pregnancy should be borne in mind whenever late-pregnancy ultrasonography shows the above-mentioned characteristic ultrasonic findings.

Adult↗

Characteristics of hospitalized heroin smokers and heroin injectors in Taiwan.

BACKGROUND: Heroin usage in Taiwan has been under-investigated. Use of the same drug by different routes provides an opportunity for examination of drug behavior and complications related to the drug itself and to the different routes of administration. METHODS: A sample of 245 hospitalized heroin users received semi-structured interviews, drug screen urine tests, serological screens for hepatitis B infection, and liver function tests. The sample was divided into a smokers group and an injectors group for comparison. RESULTS: The heroin injectors had lower educational status, spent less money on day-to-day heroin usage, but had longer drug-using careers than the heroin smokers. There was a trend for injectors to have a higher rate of abnormal liver function than the smokers although there was no significant difference in the prevalence of hepatitis B infection. CONCLUSION: Major differences exist between heroin smokers and heroin injectors. Therefore harm reduction intervention for heroin users should take account of the different routes of administration. A comprehensive survey of risk factors relating to hepatic dysfunction in heroin addicts in Taiwan is indicated.

Adolescent↗

Differentially expressed snoRNAs in Bungarus multicinctus (Taiwan banded krait).

Twenty novel snoRNAs forming extensive sequence complementarities to mature 5S rRNA were identified from Bungarus multicinctus by reverse transcription-polymerase chain reaction. It was found that the snoRNA species were differentially transcribed in different tissues as evidenced by single stranded conformational polymorphism analysis and direct nucleotide sequence analysis. Although the diversity in the sequences of snoRNAs is observed, comparison of these snoRNA genes reveals that the regions involved in binding to 5S rRNA are highly conserved and form two 12-nt-15-nt tracts of complementarity to phylogenetically invariant sequences in eukaryotic 5S rRNAs. Nevertheless, the lower conservation of box C/D or box H/ACA in these snoRNAs was observed. Likewise, the sequences in several fish and human genes forming perfect duplexes with 5S rRNA also did not highly retain these box elements. These results may infer that the box elements are dispensable for the function of snoRNA species identified in the present study. Moreover, the novel finding of the differentially expressed snoRNA variants in B. multicinctus suggests that the snoRNA genes are selectively processed in different tissues and are likely associated with tissue-specific regulation of their host gene transcripts.

Animals↗

Reversible metabolism of clozapine and clozapine N-oxide in schizophrenic patients.

1. To characterize the interconversion process between clozapine and its metabolite clozapine N-oxide (CNO), eight healthy male schizophrenics were administered a single dose of clozapine or CNO in a randomized crossover manner. 2. Using a general pharmacokinetic model for the interconversion process, the mean total clearances of clozapine and CNO were 28.45 L/hr and 45.30 L/hr, respectively. These values were similar to the values obtained by the usual model-independent method of pharmacokinetic analysis. 3. When administered clozapine, mean CNO plasma concentrations of 17.7 +/- 16.4 ng/ml were slightly lower than the other clozapine metabolite-desmethylclozapine (DCLOZ) plasma levels of 24.4 +/- 8.6 ng/ml at the 12 hour time point. When CNO was administered, plasma concentrations at the 12 hour time point of clozapine were twice the amount of CNO (28.1 +/- 8.9 ng/ml vs 14.4 +/- 8.8 ng/ml). 4. DCLOZ plasma concentrations were detected in all patients upon clozapine administration. Upon CNO administration, only one patient had detectable plasma DCLOZ levels. 5. The interconversion process of clozapine and CNO could partially account for the wide interpatient variability reported for clozapine plasma concentrations in schizophrenic patients.

Adult↗

Cytotoxicity of sodium fluoride on human oral mucosal fibroblasts and its mechanisms.

Because sodium fluoride (NaF) is widely used for prevention of dental caries, pathobiological effects of NaF were investigated on human oral mucosal fibroblasts. The results showed that NaF was cytotoxic to oral mucosal fibroblasts at concentrations of 4 mmol/L or higher. Exposure of cells to NaF for 2 h also inhibited protein synthesis, cellular ATP level and functional mitochondrial activities in a dose-dependent manner. However, incubation of cells with NaF up to 12 mmol/L for 2 h depleted only 13% of cellular glutathione level. The IC50 of NaF on cellular ATP level was about 5.75 mmol/L. Preincubation of the cells with pyruvate and succinate did not protect cells from NaF-induced ATP depletion. At concentrations of 4 mmol/L, 8 mmol/L and 12 mmol/L, NaF inhibited 31%, 56% and 57% of mitochondrial functions, respectively, after 2 h incubation. No significant inhibition for NaF was found at concentrations lower than 2 mmol/L (40 ppm). These results indicate that NaF can be toxic to oral mucosal fibroblasts in vitro by its inhibition of protein synthesis, mitochondrial function and depletion of cellular ATP. Because of repeated and long-term usage of NaF, more detailed studies should be undertaken to understand its toxic effects in vitro and in vivo.

Adenosine Triphosphate↗

An evaluation of whole blood testing for Helicobacter pylori in general practice.

BACKGROUND: Rapid whole blood tests for Helicobacter pylori infection were developed to assist in the management of patients with dyspepsia in general practice. However, they have not been extensively tested in this setting. AIM: To investigate the test characteristics of the BM-Test (Helisal Quick Test) when used in general practice. METHOD: One hundred and ten dyspeptic patients attending local general practitioners were recruited into the study. The BM-Test was administered by the general practitioner at the screening visit according to standard instructions supplied with the test kit. The patient was then referred to Nepean or Mornington Peninsula Hospitals for further assessment. including a 14C-urea breath test. The test kit was forwarded to the appropriate hospital centre for an independent, blinded reading. The sensitivity and specificity of the BM-Test were evaluated against the results of the 14C-UBT. RESULTS: Based on general practitioner readings, the BM-Test had a sensitivity of 59.3% and a specificity of 90.2%. The positive and negative predictive values were 87.5% and 65.7%, respectively. When based on independent readings, sensitivity rose to 71.2% and specificity fell to 88.2%. The BM-Test was more sensitive for older patients than for younger patients when based on both the general practitioner and independent readings. CONCLUSION: The BM-Test performs below the generally recommended sensitivity and specificity of 90% required for clinical practice.

Adult↗

Prevalence of Helicobacter pylori in a representative Anglo-Celtic population of urban Melbourne.

The aims of this study were to assess the prevalence of Helicobacter pylori and its relationship with different epidemiological factors in an Anglo-Celtic Australian population in the Melbourne urban area. Two hundred and seventy-three (120 men and 153 women with a mean age of 55.6 and range of 20 to 80 years) of 396 eligible subjects randomly sampled from the telephone directory were studied. An ELISA technique was used to detect H. pylori immunoglobulin (Ig)G antibody and self-administered questionnaires were completed. The overall seroprevalence of H. pylori was 38% and increased with age from 18% (20-30 years old) to 53% (over 70 years; P < 0.0001). The acquisition of H. pylori infection was 1% per year. The prevalence of H. pylori was 48% in men and 30% in women (P < 0.01). The frequency of H. pylori was also associated with low-income levels and current smoking, but was not associated with peptic ulcer disease history. The prevalence of H. pylori infection in a representative Australian population was found to be similar to other developed countries. The risk factors for H. pylori infection include age, male sex, low household income and a smoking habit. No correlation between H. pylori status and dyspepsia symptoms were observed.

Adult↗

The prevalence of Helicobacter pylori in practising dental staff and dental students.

Recent studies suggest Helicobacter pylori is spread by faecal-oral or oral-oral transmission. Gastroenterologists who are exposed to gastric secretions and saliva have a high prevalence of H. pylori infection. Venous blood was obtained from 92 dentists, 40 dental nurses, 33 fifth year and 30 first year dental students. An ELISA assay was used to detect H. pylori IgG antibodies. Results were compared with an age and sex matched normal population. The prevalence of H. pylori infection in dentists, dental nurses, fifth year dental students and first year dental students were 23 per cent, 18 per cent, 18 per cent and 16 per cent, respectively. There were no significant differences when compared with the normal population controls. The prevalence of H. pylori antibody was not significantly increased with years of practice or patient contact time in dentists and dental nurses. Helicobacter pylori infection is uncommon in dental professionals working in the oral cavity.

Adolescent↗

Areca nut extract inhibits the growth, attachment, and matrix protein synthesis of cultured human gingival fibroblasts.

Betel quid chewing is a popular oral habit in India, South Africa, and many Southeast Asian countries. The effects of areca nut (AN) extract on the growth, attachment, and protein synthesis of healthy human gingival fibroblasts (GF) were investigated to determine why betel quid (BQ) chewers have higher prevalence of periodontal disease than non-chewers. Twenty-four hour exposure of human GF to AN extract (> 200 microg/ml) in culture led to the formation of numerous intracellular vacuoles. As analyzed by modified MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide] assay, AN extract significantly suppressed the growth of GF over 5 days of incubation in a dose-dependent manner. At concentrations of 50 and 300 microg/ml, AN extract suppressed the growth of GF with 30% and 57% (P < 0.05), respectively. AN extract also significantly suppressed the synthesis of [3H]proline incorporation into trichloroacetic acid (TCA) precipitated proteins. At concentrations of 200, 400, and 600 microg/ml, AN extract suppressed the protein synthesis with 33%, 58%, and 63% of inhibition (P < 0.05), respectively. Preincubation of cells in a medium containing AN extract for 2 hours inhibits the subsequent attachment of cultured GF to type I collagen at the 50% inhibitory concentration (IC50) which is about 720 to 798 microg/ml. Considering the frequent consumption of BQ throughout the day, impairment of sequential fibroblast functions by BQ ingredients is a potential mechanism through which BQ chewing exert a deleterious effect to the gingival tissues.

Areca↗

Drug use patterns and gender differences among heroin addicts hospitalized for detoxification.

BACKGROUND: There has been a surge of heroin abuse in Taiwan in recent years making it necessary to study and understand the characteristics, drug use patterns and behavior among heroin users. MATERIALS AND METHODS: Two hundred and eighty-three patients hospitalized for heroin detoxification received a diagnostic interview and a semi-structured interview which rendered the demographic information, medical history, and patterns of and reasons for heroin use. Differences between male and female drug users were also compared. RESULTS: More than half of the subjects (54.3%) were unemployed. The percentage of unemployment of female patients was significantly greater than that of male patients (75.9% vs. 48.0%, p<0.05). Women were significantly younger (p<0.001) and had a significantly earlier (p< 0.001) onset of heroin use than men. About one-third of the subjects (33.9%) were multiple drug users, with amphetamines as the most common (79.2%) concomitant drug of abuse. More men reported curiosity as the reason for first use, while more women reported peer influence as the reason for first use. CONCLUSION: This study showed that significant gender differences in employment status, age of first use, and reasons for drug use among heroin addicts. Further exploration of gender and cross-cultural differences could have important theoretical and treatment implications.

Adult↗

Oral manifestations of human immunodeficiency virus-infected patients in Taiwan.

To understand the characteristic clinical features of human immunodeficiency virus (HIV)-related oral lesions and determine the prevalence of various oral lesions in HIV-infected patients in Taiwan, we conducted a cross-sectional study of 207 HIV-infected patients at the Taipei Municipal Institute for Venereal Disease Control. Overall, 108 (52.2%) patients had at least one oral lesion. The most common oral manifestation of HIV infection among these 207 patients was oral hairy leukoplakia (OHL, 29.5%), followed by candidiasis (12.1%), xerostomia (10.6%), aphthous ulcers (8.7%), and linear gingival erythema (5.8%). Less frequently encountered oral lesions included leukoplakia (1.9%), papilloma (1.4%), necrotizing ulcerative periodontitis (1.0%), Kaposi's sarcoma (1.0%), herpes simplex (0.5%), Burkitt's lymphoma (0.5%), and parotid gland enlargement (0.5%). Thirty-one (15%) patients had multiple oral lesions. Patients with oral candidiasis or multiple oral lesions had significantly lower mean CD4 lymphocyte counts and CD4/CD8 lymphocyte ratios than those without any oral lesions (p < 0.05). Chi-square analysis revealed that patients with CD4 lymphocyte counts below 200 cells/mm3 were more prone to have OHL (p < 0.002), oral candidiasis (p < 0.001) and multiple oral lesions (p < 0.001). Those with CD4/CD8 lymphocyte ratios below 0.4 were more likely to have OHL (p < 0.02), oral candidiasis (p < 0.01) and multiple oral lesions (p < 0.02) than those with higher counts. In conclusion, the occurrence of oral lesions, especially OHL and oral candidiasis, is fairly common in Taiwanese HIV-infected patients.

Adolescent↗

Double-blind randomised controlled trial of lofexidine versus clonidine in the treatment of heroin withdrawal.

Lofexidine is an analogue of clonidine, an agonist at the alpha 2 noradrenergic receptor. Reports from preliminary open studies have suggested that it may be at least as effective as clonidine in the management of opiate withdrawal, and without the same limitation of postural hypotension. We report on a randomised double-blind comparison of lofexidine versus clonidine in the treatment of heroin withdrawal. A total of 80 hospitalized heroin addicts were randomly assigned to treatment with lofexidine or clonidine during in-patient opiate withdrawal. Maximum daily doses were 1.6 mg for lofexidine and 0.6 mg for clonidine. There was marked diurnal variation of withdrawal symptoms with severity being greatest at the daytime reading at 16.00 h and being markedly less at the night-time reading (recorded at 08.00 h). Lofexidine and clonidine were equally effective in treating the withdrawal syndrome. However, significantly more problems relating to hypotension were encountered with subjects on clonidine, with twice as many instances of withholding medication due to hypotension in the clonidine group. Better treatment retention rates were seen in the lofexidine group, although no difference was found in the proportion who had reached minimal symptom severity by the time of their discharge. We conclude that lofexidine and clonidine are equally effective, but with significantly fewer hypotensive problems with lofexidine. Further benefit from lofexidine may be possible with revised dosing regimens. Outpatient studies of lofexidine are now indicated.

Adult↗

Immunolocalization of interstitial collagenase (MMP-1) and tissue inhibitor of metalloproteinases-1 (TIMP-1) in radicular cysts.

To investigate the mechanisms involved in expansion of radicular cysts, monoclonal antibodies against interstitial collagenase (MMP-1) and tissue inhibitor of metalloproteinases-1 (TIMP-1) were used to localize the sites of MMP-1 and TIMP-1 expression in 30 radicular cysts. Positive MMP-1 staining was detected in the lining epithelium and subepithelial fibroblasts, macrophages, endothelial cells and osteoblasts/osteocytes in all specimens. Positive TIMP-1 staining was identified in osteoblasts/osteocytes and endothelial cells of all specimens, and in the lining epithelium and subepithelial fibrous connective tissue wall of five radicular cysts with an intense inflammatory cell infiltrate. The number and distribution of positive cells for MMP-1 or TIMP-1 varied widely among individual specimens, but strong immunostaining was constantly detected at sites with prominent subepithelial inflammation. Results here support the hypothesis that MMP-1 may play an important role in the expansion of radicular cysts. The absence of TIMP-1 expression in lining epithelium and subepithelial fibroblasts and macrophages in most cases studied indicated that an imbalance between MMP-1 and TIMP-1 production may lead to radicular cyst expansion.

Antibodies, Monoclonal↗

Carotid floating plaques associated with multiple cerebral embolic strokes. Case reports.

The authors describe 2 patients with multiple cerebral infarcts and hemorrhagic transformation caused by artery-to-artery emboli. Ulcerated plaques with free-floating thrombus adherent to the plaque were detected at the carotid bifurcation by duplex sonography. No other embolic source could be found. One patient developed an occipital infarction due to carotid emboli passing through a fetal-type posterior communicating artery. Both patients recovered well without recurrence of stroke or transient ischemic attack with antiplatelet treatment only. Follow-up carotid duplex sonography showed disappearance of floating thrombus in 1 patient and consolidation of the lesion in the other.

Adult↗

Severe limb reduction defects after uterine lavage at 7-8 weeks' gestation.

A 35-year-old multiparous Chinese woman underwent a uterine lavage procedure for prenatal sex determination at 7-8 weeks' gestation. The baby was delivered by elective Caesarean section because of breech presentation at 38 weeks' gestation. The child weighed 2425 g and had severe reduction defects of all four limbs. This case warrants advising prospective patients of a possible association and encouraging practitioners to mount a careful prenatal ultrasonography and postnatal follow-up of all pregnancies investigated by prenatal diagnostic uterine lavage.

Adult↗

Assessment of trophoblastic flow in abnormal first trimester intrauterine pregnancy.

BACKGROUND: The use of color Doppler sonography in assessing feto-maternal circulation during pregnancy has recently been advocated. However, studies of evaluation of trophoblastic flow in the first trimester of pregnancy, with color Doppler sonography, are rare. The objects of this study were to assess the trophoblastic flow in first trimester pregnancy failure by using transvaginal color Doppler sonography, and attempted to elucidate the pathophysiology of early feto-maternal circulation. METHODS: One hundred and five cases of first trimester intrauterine pregnancy were enrolled in this study, including 34 cases of blighted ova, 50 missed abortions and 21 normal pregnancies. All patients received transvaginal sonography (Acuson 128, 5MHz). First, color Doppler was mapped and then trophoblastic flow (TBF) was detected and the resistance index (RI) was calculated. Main uterine artery (UA) flow was measured in the later part of this study. Serial sonographic examinations with serum beta-human chorionic gonadotropin (beta-hCG) levels were obtained to confirm a diagnosis of pregnancy failure. Discrepancy in gestational age calculated by the last menstrual period and by sonar measurement was recorded for analysis. The aborted tissues were submitted for karyotyping from six cases of normal pregnancy, 11 cases of blighted ovum and 22 cases of missed abortion. RESULTS: Preliminary result showed TBF can be detected at as early as the fifth week of gestation. The RIs of TBF and UA seemed to decrease; however, serum beta-hCG levels increased as gestational age advanced in normal pregnancies. This change was not shown in the abnormal groups. No significant difference in the RI of TBF or UA flow was noted between normal and abnormal pregnancies. Also the result of karyotyping did not correlate well with the RIs of TBF and UA, and serum beta-hCG levels. CONCLUSIONS: The assessment of feto-maternal circulation in early pregnancy does provide information on the physiology of early normal placentation, but not of the early pregnancy failure. Limited case numbers and different time intervals between fetal demise and sonographic diagnosis may play roles in the above findings.

Chorionic Gonadotropin, beta Subunit, Human↗