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Biomedical subjects

S K Lin

Publications and source records attributed to S K Lin.

At least 19 recordsLinked to original sources

Comparisons of norcantharidin cytotoxic effects on oral cancer cells and normal buccal keratinocytes.

Norcantharidin (NCTD) is the demethylated analogue of cantharidin. In this study, multi-parameter assessments of morphological alterations, clonogenic efficiency, cell growth curves, DNA synthesis, and DNA strand break were employed to determine and compare the cytotoxic effects of NCTD on oral cancer KB cell line and normal buccal keratinocytes. The results showed NCTD induced significant cytotoxicity in KB cells after 24 h of exposure. Normal buccal keratinocytes were more resistant to NCTD induced cytotoxicity. The IC(50) of 24 h NCTD treatment for KB and keratinocytes were 15.06 and 216.29 microg/ml, respectively with a keratinocyte/KB selective index of 14.36. Anoikis and membrane blebbing, morphological characterization of apoptosis, were observed in about 90% of KB cells after exposure to 100 microg/ml of NCTD for 24 h compared to about 30% in keratinocytes. In addition, inhibition of colony formation was noted in KB cells even when exposed to low concentration of drug (5 microg/ml) for a short period of time (6 h). NCTD inhibited subsequent cell proliferation in KB but growth of normal keratinocytes was retarded only temporarily. NCTD inhibited DNA synthesis in both KB and normal keratinocytes. However, keratinocytes were more sensitive to DNA synthesis inhibition by low dose of NCTD. Significant DNA strand break was noted in KB cells only after cell viability was reduced to less than 60% of the control. In comparison, normal keratinocytes were resistant to NCTD induced DNA strand break. These results indicated KB cells were more sensitive to NCTD induced cytotoxicity compared to normal keratinocytes. NCTD may be of value in treating oral cancers. The underlying mechanisms of the differential actions of NCTD on these two cell types are worthy of further investigations.

Bridged Bicyclo Compounds, Heterocyclic↗

Pre-morbid characteristics and co-morbidity of methamphetamine users with and without psychosis.

BACKGROUND: The long-term use of methamphetamine (MAMP) can result in psychosis but it is not clear why some individuals develop psychotic symptoms, while others use MAMP regularly over long periods and remain unscathed. We set out to characterize MAMP users and to examine the relationship of pre-morbid personality, pre-morbid social function and other psychiatric disorders to MAMP psychosis. METHOD: Four hundred and forty-five amphetamine users were recruited from a psychiatric hospital and a detention centre in Taipei, and were assessed with the Diagnostic Interview for Genetic Studies (DIGS). Their parents were interviewed with the Premorbid Schizoid and Schizotypal Traits (PSST) and the Premorbid Social Adjustment (PSA) schedules. Pre-morbid characteristics and psychiatric co-morbidity were compared between the MAMP users with a lifetime diagnosis of MAMP psychosis and those without. RESULTS: The MAMP users with psychosis presented a clinical picture which mimicked the positive symptoms of schizophrenia: 85% had auditory hallucinations; 71% persecutory delusions; 63% delusions of reference. Compared with their non-psychotic counterparts, these MAMP users were younger at first MAMP use, used larger amounts of MAMP, had a significantly higher mean PSST score, and higher rates of major depressive disorder, alcohol dependence and antisocial personality disorder. CONCLUSIONS: Earlier and larger use of MAMP was associated with increased risk of psychosis. Our data are also compatible with the view that pre-morbid schizoid/schizotypal personality predisposes MAMP users to develop psychosis, and that the greater the personality vulnerability, the longer the psychosis will persist.

Adolescent↗

A rapid-release 50-mg tablet-based 13C-urea breath test for the diagnosis of Helicobacter pylori infection.

BACKGROUND: Recently, a rapid-release 100-mg 13C-urea tablet with citrate supplement (Diabact UBT) showed excellent performance in a European population. AIM: To investigate the accuracy of a 50-mg tablet-based 13C-urea breath test protocol. METHODS: : Consecutive dyspeptic patients referred for upper endoscopy were recruited. 13C-Urea breath test was performed using a 50-mg 13C-urea tablet (Diabact UBT) and compared with the gold standard (rapid urease test and histology). Baseline, 10-min, 20-min and 30-min breath samples were collected in all cases. The cut-off values at each measurement interval were determined by three standard deviations above the mean excess delta 13CO2 excretion of Helicobacter pylori-negative patients. RESULTS: Two hundred patients (150 before therapy and 50 after therapy) were available for analysis, with a mean age of 48.4 years, and 99 patients (50%) were H. pylori positive. The sensitivity and specificity of the 50-mg tablet-based 13C-urea breath test at 10 min, 20 min and 30 min were 100% and 98%, 100% and 100%, and 100% and 98%, respectively. CONCLUSION: A 20-min, 50-mg tablet-based 13C-urea breath test (Diabact UBT) protocol is highly accurate for the diagnosis of H. pylori infection.

Adolescent↗

Novel mutation and prenatal sonographic findings of glutaric aciduria (type I) in two Taiwanese families.

Glutaric aciduria type I (GA I) is an autosomal recessively inherited inborn error with a defect of the enzyme glutaryl-CoA dehydrogenase (GCDH), which has never been diagnosed prenatally in Taiwanese patients. We present the prenatal sonographic findings and mutational analysis data of three children in two Taiwanese families. One patient from each family was diagnosed postnatally due to macrocephaly and neurological deterioration at 4 months and 10 months, respectively. The third child, sister of the first patient, was diagnosed prenatally at 11 weeks' gestation through chorionic villus sampling (CVS). Molecular analysis revealed that the fetus and child in Family 1 were homozygous for a common mutation, IVS10 -2A>C, which has not been reported in the Caucasian population. The patient in Family 2 was a compound heterozygote for IVS10 -2A>C and a novel mutation 749T>C (L238P). After genetic counseling, the couple decided to continue the second pregnancy. However, dilatation of quadrigeminal cistern (QC) and suspicious macrocephaly were noted at 30 weeks. Progressive dilatation of the QC associated with macrocephaly, fronto-temporal atrophy and wide space of perisylvian fissure were found in the follow-up scans. The affected girl was delivered at 37 weeks' gestation by cesarean section. Postnatal magnetic resonance imaging (MRI) studies confirmed the prenatal sonographic findings. With prenatal sonographic findings and mutational analysis presented in the present cases, the feasibility of prenatal diagnosis of GA I in high-risk pregnancy can not be overlooked.

Adult↗

Cochlear vertebral entrapment syndrome: a case report.

The authors describe a patient with isolated involvement of vestibulocochlear nerve by a huge vascular loop from vertebral dolichoectasia. No other neurological deficit was found except for unilateral hearing loss. Abnormal brainstem auditory evoked potential study indicated a retrocochlear lesion. The brain computed tomography (CT) and magnetic resonance imaging (MRI) studies demonstrated an abnormally enhanced vascular lesion impinged on the left porus acusticus with a displacement of the brainstem to the right. There was no infarction in the brainstem. A cerebral angiography demonstrated a megadolichoectatic horizontal loop at the intracranial portion of the left vertebral artery. There was no thrombus or atherosclerosis in the vertebrobasilar system. A mechanical compression by a vascular loop is the only possible pathogenesis for hearing loss. The authors diagnose this condition as cochlear vertebral entrapment syndrome.

Aged↗

Prenatal diagnosis of a rare variant of hypospadias and review of the literature.

We present a case of a variant of hypospadias, diagnosed prenatally at 21 weeks' gestation, in which the penis and scrotum appeared normal but there was a cyst-like lesion and a urethrocutaneous fistula on the ventral side of the penis. Detailed sonographic examination and karyotyping confirmed this was an isolated lesion and helped the parents to decide on continuation of the pregnancy.

Adult↗

The Chinese version of the Davidson Trauma Scale: a practice test for validation.

The Chinese version of the Davidson Trauma Scale (DTS-C) was developed to respond to the need of Chinese-speaking individuals. The DTS is a validated self-rating scale used in the diagnosis of posttraumatic stress disorder (PTSD). The DTS-C is translated from DTS through a two-stage translation. Subjects were drawn from a sample of 210 survivors of the 21 September 1999, Chi-Chi Earthquake. The scale showed good internal consistency (Cronbach's alpha = 0.97) and test-retest reliability (r = 0.88). Concurrent validity was obtained against the clinical diagnostic interview, with a diagnostic accuracy of 0.85 at DTS-C score of 44. It showed that the sensitivity was 0.9, specificity 0.81, positive likelihood ratio 4.74, and negative likelihood ratio 0.12. The recommended stratum-specific likelihood ratios were 0.10 (95% CI: 0.05-0.20) for the score range 0-39, 4 (2.22-7.23) for the score range of 40-59, and 6.14 (3.42-11.02) for the scores above 60. In PTSD diagnosed subjects, the factor structures closely resembled the DSM-IV grouping of PTSD symptoms. The psychometric strength of DTS-C is reliable for its future use, particularly for screening for subjects with possible diagnosis of PTSD.

Adolescent↗

Induction of dental pulp fibroblast matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1 gene expression by interleukin-1alpha and tumor necrosis factor-alpha through a prostaglandin-dependent pathway.

Matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) are involved in the degradation of extracellular matrix in many inflammatory diseases. Little is known regarding the expression of these mediators in dental pulp fibroblasts. The effects of proinflammatory cytokines (interleukin (IL)-1alpha and tumor necrosis factor-alpha (TNF-alpha)) and prostaglandin E2 (PGE2) on pulp fibroblast MMP-1 and TIMP-1 gene expression were investigated. Northern hybridization showed that IL-1alpha and TNF-alpha induced significant MMP-1 gene expression, with only little effect on TIMP-1 gene. Exogenous PGE2, however, upregulated TIMP-1 mRNA synthesis but not MMP-1. Concomitant addition of IL-1alpha and PGE2 or TNF-alpha and PGE2 suppressed MMP-1 mRNA production, compared with the groups treated with IL-1alpha or TNF-alpha alone. In contrast, PGE2 enhanced the upregulatory effects of TIMP-1 mRNA by IL-1alpha or TNF-alpha. Furthermore, cytokine stimulation of MMP-1 and TIMP-1 gene expressions can be enhanced or blocked by indomethacin, respectively, and reversed by exogenous PGE2. These results suggested that cytokine-stimulated MMP-1 and TIMP-1 gene expression in dental pulp fibroblasts was mediated, at least in part, by a prostaglandin-dependent pathway. The differential regulation of IL-1alpha or TNF-alpha-induced MMP-1 and TIMP-1 mRNA synthesis, as well as the direct upregulation of TIMP-1 gene expression by PGE2, also implied that prostaglandin may serve as a protective mechanism from excessive tissue breakdown during pulpitis.

Anti-Inflammatory Agents, Non-Steroidal↗

Matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1 gene expressions and their differential regulation by proinflammatory cytokines and prostaglandin in nasal polyp fibroblasts.

Chronic inflammation of the paranasal sinus leads to nasal polyp (NP) formation. In this study, we investigated the effect of stimulation of the proinflammatory cytokines interleukin-1alpha (IL-1alpha) and tumor necrosis factor-alpha (TNF-alpha) and prostaglandin (PG) E2 on the production of messenger RNA (mRNA) of matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-I (TIMP-1) in nasal polyp fibroblasts (NPFs) and nasal mucosa fibroblasts (NFs). The mRNAs of IL-1alpha, TNF-alpha, MMP-1, and TIMP-1 in 40 surgical specimens of NPs were studied by in situ hybridization to corroborate the in vitro findings. The results indicated a significant amount of constitutive MMP-1 mRNA in NPFs and cytokine-induced MMP-1 steady-state mRNAs in NFs. The effect of stimulation of cytokines on TIMP-1 mRNA synthesis was unremarkable in NPFs and NFs. Exogenous PGE2 enhanced cytokine-stimulated MMP-1 mRNA synthesis in NPFs. In situ hybridization revealed that cells expressing MMP-1 and TIMP-1 mRNAs (primarily plasma cells, fibroblasts, and endothelial cells) gathered around areas with loose stroma, suggestive of rapid extracellular matrix degradation. These data suggest that the pathogenesis of nasal polyposis could be related to production of MMP-1 and consequent promotion of matrix collagenolysis.

Cytokines↗

Efficacy and safety of zotepine for the treatment of Taiwanese schizophrenic patients: a double-blind comparison with haloperidol.

BACKGROUND AND PURPOSE: Zotepine is claimed to be a neuroleptic drug with atypical features. However, there have been few double-blind studies in Asian patients. The purpose of this study was to compare the efficacy and safety of zotepine and haloperidol in Taiwanese patients with schizophrenia. PATIENTS AND METHODS: Patients with positive symptoms (n = 70) were enrolled into this double-blind, randomized study. Each patient received either zotepine 150 mg/day or haloperidol 9 mg/day. The Positive and Negative Syndrome Scale (PANSS), Brief Psychiatric Rating Scale (BPRS), and Clinical Global Impression (CGI) were assessed on Days 0, 3, 7, 14, 28, and 42 after the start of treatment. Adverse events were recorded during the trial period. The analyses were carried out on an intent-to-treat basis with the last observation carried forward. RESULTS: In terms of the score reduction in the PANSS, BPRS, and CGI, all analyses indicated that there were no significant differences between the groups at the end of the trial. Patients who received zotepine had no acute dystonia and less severe parkinsonism (p < 0.05 or 0.10), but significantly more dizziness, body weight gain, and pulse rate increase. CONCLUSION: In this 6-week trial, zotepine at 150 mg/day was as efficacious as haloperidol 9 mg/day in the treatment of Taiwanese patients with schizophrenia. Zotepine treatment produced fewer extrapyramidal symptoms but had a greater frequency of sedative effects compared to haloperidol.

Adult↗

Norcantharidin-induced post-G(2)/M apoptosis is dependent on wild-type p53 gene.

Norcantharidin (NCTD), a synthetic analogue of phosphatase type 2A inhibitors, cantharidin, was shown to have limited effects in treating human and animal tumors. The tumor cell killing mechanisms by norcantharidin, however, remain unclear. In this report, we wished to investigate the mechanisms of norcantharidin-mediated cytotoxicity. Effort was made to investigate whether norcantharidin exerted its cytotoxicity through a p53-dependent or -independent mechanism. RT-2 (wtp53) and U251 (mutant p53) glioblastoma cell lines were exposed to norcantharidin at different dosages. Time-course fluorescent-activated cell sorting (FACS) analysis showed that high doses of norcantharidin arrested the cells at the G(2)/M phase and subsequent post-G(2)/M apoptosis in RT-2 cell line. In comparison, the U251 cell line was found resistant to norcantharidin-induced cytotoxicity. Restoring wild-type p53 gene function in the U251 cell line after adenoviral infections induced tumor cell cytotoxicity after exposure to norcantharidin. These results showed that norcantharidin kills tumor cells efficiently corresponding to their endogenous p53 gene status. The results also showed the feasibility of using adenoviral p53 gene therapy to enhance chemosensitivity of tumor cells to norcantharidin.

Antineoplastic Agents↗

Expression of p16(INK4A) induces dominant suppression of glioblastoma growth in situ through necrosis and cell cycle arrest.

Tumor suppressor genes may represent an important new therapeutic modality in the treatment of human glioblastoma (GBM). p16(INK4A) is a tumor suppressor gene with mutation and/or deletion found in many human tumors, including glioblastomas, melanoma, and leukemias. RT-2 rat GBM cell line was used to investigate if the p16 gene induces dominant suppression of glioblastoma growth. Close to 100% of tumor cells were infected by high titer pCL retrovirus encoding the full-length human p16 cDNA at 5 m.o.i. Infected cells showed a 98% reduction in colony forming assay and a 60% reduction in growth curves in vitro compared to vector control. Exogenous overexpression of p16 induced hypophosphorylation of Rb protein by Western blot analysis. Intracranial injection of p16-infected tumor cells into syngeneic rats resulted in a 95% reduction in tumor volume compared to the controls. Intratumoral injection of p16 retrovirus resulted in tumor necrosis and prominent human p16 transgene expressions. Proliferation marker PCNA was not detected in these human p16-expressed RT-2 tumor cells, suggesting the cells were unable to enter into S phase after p16 expression. In addition, direct repeat intracranial injections of p16 retrovirus prolonged animal survival 3.2-fold compared to the controls (48.4 +/- 13.4 vs 15.0 +/- 2.1 days, p < 0.001). Two out of ten rats were found with dormant tumors at day 60 after p16 retrovirus injection. These results showed that p16 is effective in inhibiting GBM growth in situ. The mechanisms of tumor growth reduction and necrosis in vivo might be due to G1 arrest triggered by p16 expression.

Animals↗

Immunolocalization of macrophages and transforming growth factor-beta 1 in induced rat periapical lesions.

Apical periodontitis was induced in Wistar rats by exposing the pulp chamber of right mandibular first molars to the oral environment. Animals were killed 0, 5, 10, 15, 20, 30, 60, and 80 days after lesion induction. Microradiographic and automated image analysis showed that the lesions expanded significantly in a time-dependent manner from day 0 to day 20 (0.039 mm2/day, p < 0.05, active phase) and stabilized thereafter (chronic phase). A linear regression test revealed a positive correlation between the numbers of ED-1 positive macrophage per microscopic high power field and the periapical lesion size during the active phase (r = 0.98, p < 0.01). Immunohistochemical studies showed that transforming growth factor-beta 1 positive macrophages distributed around the root apex and areas showing bone resorption during active lesion phase, whereas TGF-beta 1-positive osteoblasts were detected during the chronic stage (days 30, 60, and 80 after pulp exposure). Histologically TGF-beta 1 positive osteoblasts possessed a large, round nucleus as well as an abundant cytoplasm and located in close vicinity to areas exhibiting reparative bone formation. These results suggest that macrophages may play important role(s) in the initiation and development of periapical lesions and TGF-beta 1 may play dual roles in both bone resorption and deposition in induced rat periapical lesions.

Acute Disease↗

A comparison of the morphological changes after Nd-YAG and CO2 laser irradiation of dentin surfaces.

The purpose of this study was to compare the morphological changes after Nd-YAG and CO2 laser irradiation on dentin surfaces with or without the smear layer. Eighty-one 3-mm-thick dentin specimens collected from the middle third of molar crowns were used. The dentin surfaces were ground to #320, #400, and #600 grit in series to create a smear layer. Half of the specimens were treated with 14% EDTA for 2 min to remove the smear layers. The lasers were applied on each specimen perpendicularly with 1-mm focus distance to the dentin surface for 4 s. The parameters for the Nd-YAG laser were 50 mJ, 100 mJ, and 150 mJ at 10 pps, 20 pps, and 30 pps, and for the CO2 laser were 2 W, 3 W, and 4 W at 5 ms x 20 pps, 10 ms x 10 pps, 20 ms x 20 pps, 50 ms x 2 pps, 100 ms x 2 pps, and 200 ms x 2 pps. The results showed that the Nd-YAG laser caused crater and melting of the dentin surface, especially in dentin specimens with smear layers. The CO2 laser produced extensive cracking lines on dentin surfaces with a smear layer, whereas surface erosion and crater formation were found on specimens without a smear layer. In conclusion, both the laser types and smear layer have a significant influence on the morphological changes of dentin surfaces irradiated by lasers.

Carbon Dioxide↗

Relative volume of the cerebellum in dolphins and comparison with anthropoid primates.

According to the 'developmental constraint hypothesis' of comparative mammalian neuroanatomy, brain growth follows predictable allometric trends. Therefore, brain structures should scale to the entire brain in the same way across mammals. Evidence for a departure from this pattern for cerebellum volume has recently been reported among the anthropoid primates. One of the mammalian groups that has been neglected in tests of the 'developmental constraint hypothesis' is the cetaceans (dolphins, whales, and porpoises). Because many cetaceans possess relative brain sizes in the range of primates comparative tests of the 'developmental constraint hypothesis' across these two groups could help to delineate the parameters of this hypothesis. In this paper, we compare relative cerebellum volumes in two cetacean species, the bottlenose dolphin (Tursiops truncatus) and the common dolphin (Delphinus delphis), with published data from anthropoid primates. We found that relative cerebellum size is significantly greater in the two dolphin species than in any of the primates, including humans. These results suggest that there is possibly expansion of brain structures independent of strictly allometric processes.

Animals↗

One-wedge convention for stereochemical representations.

We propose that various bonds (see figure below) used for specification of absolute configuration, e.g. the two types (I and II) of solid wedge and broken wedge representation most frequently seen in literature, can be replaced by only one kind of wedge, namely the solid wedge (III and IV). Only one wedge should be used when representing a quadrivalent center (IV). The three normal bonds are distributed on a cone opposite to the wedge. The flexibility, simplicity, unambiguity and usefulness for R-S specification of the one-wedge system are discussed, as well as its esthetic appeal.

Databases, Factual↗