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Biomedical subjects

M L Li

Publications and source records attributed to M L Li.

At least 19 recordsLinked to original sources
PubMed2006

alpha-Synuclein promoter RsaI T-to-C polymorphism and the risk of Parkinson's disease.

Increased alpha-synuclein expression may be involved in the pathogenesis of Parkinson's disease (PD). We investigated the association of Rep1 microsatellite and RsaI T-to-C substitution in the alpha-synuclein promoter region with the risk of PD by a case-control study. The RsaI C/C genotype and C allele were found less frequently in PD patients than in controls. A reduced risk of the Rep1-RsaI 0-C haplotype (OR = 0.57, 95% CI = 0.36-0.90) with PD was evident. The quantitative real-time PCR study showed that the alpha-synuclein mRNA expression was increased (although not significantly) in PD patients with RsaI T/T genotype or Rep1-RsaI 0-T haplotype as compared to T/C genotype or 0-C haplotype. Reporter constructs containing the RsaI C allele drove significantly lower transcriptional activity compared with the RsaI T allele in both IMR32 and 293 cells. The findings suggest that the RsaI T-to-C substitution may have a functional relevance to the susceptibility to PD.

Adult↗
PubMed2004

Optoacoustic imaging with synthetic aperture focusing and coherence weighting.

Optoacoustic imaging takes advantage of high optical contrast and low acoustic scattering and has found several biomedical applications. In the common backward mode a laser beam illuminates the image object, and an acoustic transducer located on the same side as the laser beam detects the optoacoustic signal produced by thermoelastic effects. A cross-sectional image is formed by laterally scanning the laser beam and the transducer. Although the laser beam width is generally narrow to provide good lateral resolution, strong optical scattering in tissue broadens the optical illumination pattern and thus degrades the lateral resolution. To solve this problem, a combination of the synthetic aperture focusing technique with coherence weighting is proposed. This method synthesizes a large aperture by summing properly delayed signals received at different positions. The focusing quality is further improved by using the signal coherence as an image quality index. A phantom comprising hair threads in a 1% milk solution was imaged with an optoacoustic imaging system. The results show that the proposed technique improved lateral resolution by 400-800% and the signal-to-noise ratio by 7-23 dB over conventional techniques.

Acoustics↗
PubMed2004

Genetic testing in spinocerebellar ataxia in Taiwan: expansions of trinucleotide repeats in SCA8 and SCA17 are associated with typical Parkinson's disease.

DNA tests in normal subjects and patients with ataxia and Parkinson's disease (PD) were carried out to assess the frequency of spinocerebellar ataxia (SCA) and to document the distribution of SCA mutations underlying ethnic Chinese in Taiwan. MJD/SCA3 (46%) was the most common autosomal dominant SCA in the Taiwanese cohort, followed by SCA6 (18%) and SCA1 (3%). No expansions of SCA types 2, 10, 12, or dentatorubropallidoluysian atrophy (DRPLA) were detected. The clinical phenotypes of these affected SCA patients were very heterogeneous. All of them showed clinical symptoms of cerebellar ataxia, with or without other associated features. The frequencies of large normal alleles are closely associated with the prevalence of SCA1, SCA2, MJD/SCA3, SCA6, and DRPLA among Taiwanese, Japanese, and Caucasians. Interestingly, abnormal expansions of SCA8 and SCA17 genes were detected in patients with PD. The clinical presentation for these patients is typical of idiopathic PD with the following characteristics: late onset of disease, resting tremor in the limbs, rigidity, bradykinesia, and a good response to levodopa. This study appears to be the first report describing the PD phenotype in association with an expanded allele in the TATA-binding protein gene and suggests that SCA8 may also be a cause of typical PD.

Age of Onset↗
PubMed2003

Hippocampal atrophy and T2-weighted signal changes in familial mesial temporal lobe epilepsy.

OBJECTIVE: To correlate the clinical phenotype with hippocampal volumes (HcVs) and signal changes in patients with familial mesial temporal lobe epilepsy (FMTLE). METHODS: FMTLE was defined when at least two first-degree relatives in a family had a clinical-EEG diagnosis of MTLE. Hippocampal formation measurements were performed using 1- to 3-mm coronal T1-weighted MRIs. The presence of hyperintense T2 signal was evaluated by visual analysis. For statistical analyses, analysis of variance, chi(2) test, and regression analysis were used. RESULTS: A total of 142 patients from 45 unrelated families were studied: 113 individuals with MTLE (80 with good seizure control) and 29 family members with other seizure types. There were 99 patients (69.7%) with hippocampal atrophy (HA). Sixty-seven of the 99 patients with HA also had a hyperintense T2 signal. Hyperintense T2 signal was associated with more severe HA (p = 0.04). Patients with refractory FMTLE had more frequent HA (p = 0.03) and hyperintense T2 signal (p = 0.004) and more severe atrophy (p < 0.0001). Duration of epilepsy correlated with HcV asymmetry index (r(2) = 0.12, p = 0.00008) and with the more atrophic hippocampi but not with contralateral hippocampi. CONCLUSION: In familial mesial temporal lobe epilepsy, seizure severity is variable in affected individuals. Hippocampal atrophy was present in 70% of these patients and 69% of these had an associated hyperintense T2 signal. Although hippocampal atrophy associated with abnormal T2 signal was more frequent and more severe in patients with poor seizure control, it was also frequent in affected individuals across families. These observations suggest that one or more genes resulting in familial mesial temporal lobe epilepsy predisposes both to the clinical features of mesial temporal lobe epilepsy and to the development of hippocampal sclerosis.

Adolescent↗
PubMed2002

In vitro anti-influenza virus activity of synthetic humate analogues derived from protocatechuic acid.

Two humic-like substances, the oxidative polymer of protocatechuic acid (OP-PCA) and humic acid inhibit the in vitro replication of influenza virus A/WSN/33 (H1N1) in Madin-Darby canine kidney (MDCK) cells at concentrations of no cytotoxicity. The 50% inhibitory concentration (IC50) for OP-PCA was 6.59 +/- 1.02 microg/ml when the compound was added at the stage of viral adsorption. When OP-PCA was added after virus adsorption, the IC50 was 53.27 +/- 8.12 microg/ml. The IC50 for humic acid was 48.61 +/- 7.32 microg/ml and 55.27 +/- 5.46 microg/ml respectively when the compound was added at the stage of viral adsorption or post-adsorption. In spite of structural resemblance of these two compounds, they exhibit different actions of anti-flu. The OP-PCA inhibits virus-induced hemagglutination and low pH-induced cell-cell fusion. Humic acid inhibits the endonuclease activity of viral RNA polymerase. The monomer of PCA shows no inhibition on influenza virus replication.

Animals↗
PubMed2001

The active sites of the influenza cap-dependent endonuclease are on different polymerase subunits.

The cap-dependent endonuclease of the influenza viral RNA polymerase, which produces the capped RNA primers that initiate viral mRNA synthesis, is comprised of two active sites, one for cap binding and one for endonuclease cleavage. We identify the amino acid sequences that constitute these two active sites and demonstrate that they are located on different polymerase subunits. Binding of the 5' terminal sequence of virion RNA (vRNA) to the polymerase activates a tryptophan-rich, cap-binding sequence on the PB2 subunit. At least one of the tryptophans functions in cap binding, indicating that this active site is probably similar to that of other known cap-binding proteins. Endonuclease cleavage, which is activated by the subsequent binding of the 3' terminal sequence of vRNA, resides in a PB1 sequence that contains three essential acidic amino acids, similar to the active sites of other enzymes that cut polynucleotides to produce 3'-OH ends. These results, coupled with those of our previous study, provide a molecular map of the five known essential active sites of the influenza viral polymerase.

Amino Acids, Dicarboxylic↗
PubMed2001

Gastrinoma.

Gastrinoma treatment has evolved considerably in the last 20 years. In particular, the advent of effective acid-reducing pharmacologic agents has changed the primary morbidity of this disease entity from one of acid hypersecretion to one of tumor growth and spread. Thus, while symptoms can be temporized using histamine receptor antagonists, proton pump inhibitors, or somatostatin analogs, cure can be effected only by surgical means. Recent advances in operative techniques and pre- and intra-operative imaging studies, including routine duodenotomy, somatostatin-receptor scintigraphy, and intraoperative ultrasound, have allowed for identification and subsequent resection of more than 95% of gastrinoma tumors. Most experts agree that all sporadic cases of localized gastrinoma should be excised. In addition, debulking of metastatic tumor may improve symptoms and survival when cure cannot be ascertained. There is, however, some controversy as to the surgical approach for gastrinoma found in the setting of multiple endocrine neoplasia, type 1. Because of the usual multiplicity and particular indolence of these tumors, two primary strategies have emerged: aggressive approaches have been advocated in an effort to eradicate all present and potential tumor; and less aggressive, or nonoperative, approaches have been suggested because it is unclear whether intervention offers survival or disease-free benefit in this population. We advocate surgical intervention for patients with gastrinoma and multiple endocrine neoplasia, type 1 when tumors exceed 2.5 cm in size. This tumor size has been associated with a higher likelihood of hepatic metastases, which ultimately affects survival. The role of adjuvant therapies for gastrinoma remains limited.

Anti-Ulcer Agents↗
PubMed2001

Cytotoxic 7,20-epoxy ent-kauranoids from Isodon xerophilus.

Four 7,20-epoxy ent-kaurane diterpenoids, xerophilusins G (1) and I-K (2-4), were isolated from the leaves of Isodon xerophilus, along with four known ones, enanderianin C (5), rosthorin A (6), longikaurin B (7), and rabdoternin D (8). Their structures were determined primarily using NMR spectroscopic techniques. The structure and stereochemistry of 3 were confirmed by X-ray crystallography. Compounds 4 and 7 exhibited broad cytotoxicity against four kinds of human tumor cells (K562, HL-60, HCT, and MKN-28 cells) in the range of 2.23-15.35 and 0.30-8.61 microg/ml, respectively.

Antineoplastic Agents, Phytogenic↗
PubMed2001

Elastic properties of tendon measured by two different approaches.

Elastic properties of tendon were assessed by two different approaches. Six fresh bovine Achilles tendon specimens were used. The first approach directly measured Young's modulus along the transverse direction (E(perpendicular)) and the longitudinal direction (E(parallel)), using a cyclic compression-relaxation method. Young's moduli were derived based on the measured strain and stress values. The ratio of E(parallel): E(perpendicular) at smaller strains was around 4 and decreased to 0.6 approximately 1.1 at larger strains. The second approach assumed that tendons are transversely isotropic. Three observable second-order elastic stiffness constants (c(11), c(13) and c(33)) were obtained by sound speed measurements along various propagation directions. The measured elastic stiffness constants were also correlated with results from the first approach. It was shown that the transverse isotropy assumption was valid at small strains. However, a significant discrepancy existed between the two approaches. The discrepancy was primarily due to viscoelasticity associated with the first approach.

Achilles Tendon↗
PubMed2001

Iatrogenic pheochromocytomatosis: a previously unreported result of laparoscopic adrenalectomy.

BACKGROUND: Laparoscopic adrenalectomy is now regarded as the procedure of choice for treatment of small or benign adrenal tumors, including pheochromocytoma. However, long-term outcomes have not been critically assessed. We report here 3 cases of pheochromocytomatosis recurring 3 to 4 years after laparoscopic adrenalectomy. We postulate laparoscopic-induced seeding of tumor as the mechanism of recurrence. METHODS: We retrospectively reviewed the cases of 3 patients with documented biochemical and radiolabeled metaiodobenzylguanidine evidence of recurrent pheochromocytoma after prior presumed curative laparoscopic adrenalectomy. RESULTS: Original pheochromocytomas were 5.5 to 6.5 cm in diameter. At the time of laparoscopic adrenalectomy, tumors were not believed to be malignant, based on clinical or histopathologic data. However, on 3- to 4-year follow-up, each patient developed symptoms, elevated urinary catecholamine levels, and metaiodobenzylguanidine imaging consistent with recurrence. At reoperation, multiple small tumor nodules were found in the adrenal bed near the site of the initial laparoscopic resection. The original operative notes suggested some possible method of local seeding: tumor fragmentation and spillage or excessive tumor manipulation. CONCLUSIONS: Pheochromocytoma recurrence may occur as a result of local spillage of tumor during laparoscopic adrenalectomy. The relative risk of recurrence between open and laparoscopic resection needs to be assessed. Long-term follow-up will continue to be important, regardless of operative approach.

3-Iodobenzylguanidine↗
PubMed2001

Filter-based synthetic transmit and receive focusing.

Most diagnostic ultrasonic imaging systems perform fixed focusing on transmit and dynamic focusing on receive. Such systems suffer from image quality degradation at depths away from the transmit focal zone. Several dynamic transmit focusing techniques have been previously investigated. Among them, a filter-based, retrospective focusing technique was proposed to increase the length of the transmit focal zone. In this paper, the filter-based technique is extended from dynamic receive focusing to fixed receive focusing. It is shown that the filtering technique with fixed receive focusing can achieve an image quality similar to that of dynamic receive focusing with filtering. The performance of the proposed approach is verified using real ultrasound data. It is shown that the proposed approach with fixed receive focusing requires a longer filter than that with dynamic receive focusing. Nonetheless, system complexity is greatly reduced with synthetic transmit and receive focusing because the dynamic receive focusing circuit is no longer needed.

Algorithms↗
PubMed2001

Pharmacological determinants of 9-aminocamptothecin cytotoxicity.

The camptothecins are a group of anticancer agents with a unique mechanism of action: poisoning of eukaryotic DNA topoisomerase I. 9-aminocamptothecin (9-AC), a potent water-insoluble derivative of camptothecin, is currently undergoing clinical testing. The kinetics of the active derivative 9-AC lactone in cell culture media was defined, and then 9-AC cytotoxicity against human breast (MCF-7), bladder (MGH-U1), and colon (HT-29) cancer cell lines was studied. The relationship between cytotoxic effects, drug concentration, and exposure time was then explored. For all of the three cell lines, 9-AC cytotoxicity increased with both higher drug concentrations and longer exposure times. However, when the duration of exposure was less than 24 h, cytotoxicity was limited and less than 1 log of cell killing occurred, even with very high drug concentrations. Minimal cell killing was also observed unless 9-AC concentrations exceeded a threshold of 2.7 nM. No fixed relationship between the survival fraction and the area under the drug concentration-time curve could be modeled that would fit all of the three cell lines. However, data for the three cell lines from the multiple exposure time experiments were fitted very well to the pharmacodynamic model C(n)t = k (r2, 0.90-0.99), where C is the drug concentration, n is the drug concentration coefficient, and t is the exposure time. For the three cell lines, to kill 1 log of cells, 0.30 < n < 0.85, which indicated that duration of exposure was more important than concentration. Our data support the use of 9-AC by infusion for 24 h or longer in clinical studies providing target plasma concentrations can be achieved.

Antineoplastic Agents↗
PubMed2000

Inhibitory effect of hexapeptide (RGRHGD) on platelet aggregation.

The B chain of beta-bungarotoxin 1-6 sequence, RGRHGD, presents the highest local average hydrophilicity measured by Kyte and Doolittle modeling analysis. The RGRHGD holds parts of both RGD and KGD peptides, which have been reported as having high binding affinity to GPIIb-IIIa. The present study evaluates whether the synthesized hexapeptide, RGRHGD, has an antiplatelet effect and further elucidates the possible mechanisms of action. RGRHGD dose-dependently inhibited rabbit platelet aggregation and adenosine triphosphate release induced by arachidonic acid, collagen, platelet-activating factor, thrombin, or U46619 with the IC50 range of 82.7 to 510 microg/mL. The platelet thromboxane B2 formation induced by collagen or thrombin was also significantly decreased by RGRHGD, but there was no effect on arachidonic acid-induced thromboxane B2 formation. In addition, RGRHGD also inhibited the rise of intracellular calcium level stimulated by arachidonic acid, collagen, or thrombin in Fura 2-AM-loaded platelets. The adenosine 3',5'-cyclic monophosphate level of washed platelets was not affected by RGRHGD. In conclusion, these data indicate that the inhibitory effect of RGRHGD on platelet aggregation may be due to the attenuation of thromboxane A2 formation and intracellular calcium mobilization. In addition, this study may provide a useful method of finding potential therapeutic agents by using molecular modeling analysis.

Adenosine Triphosphate↗
PubMed2000

Antimicrobial activity of synthetic all-D mastoparan M.

Mastoparan M, a tetradecapeptide toxin (INKAIAALAKKLL-NH2) from hornet venom and its D-form mastoparan M were synthesized chemically. All D- and L-mastoparan M forms were found to adopt 28% alpha-helical structures in a 30% trifluroethanol solution as shown by the circular dichroism spectrum. All-D mastoparan M caused 3H-thymidine release from labeled bacterial cells after incubation for 1 h and complete cell lysis by 4 h. Both L- and D-mastoparan M showed strong activity against gram-positive and gram-negative bacteria. All-D mastoparan M showed 2-fold higher antibacterial activity than L-mastoparan M. The effects of all-D mastoparan M on the surface morphology of Staphylococcus aureus (ATCC29213) and Escherichia coli (ATCC25922) were studied by scanning-beam electron microscopy. Blast-like bleb extrusions on the surface of some S. aureus and swellings on the end of E. coli were seen after culture with all-D mastoparan M. These findings indicated the all-D mastoparan M could kill bacteria by disrupting cells.

Anti-Bacterial Agents↗
PubMed2000

New 7,20:14,20-diepoxy ent-kauranoids from Isodon xerophilus.

Three new 7,20:14,20-diepoxy-ent-kaurane diterpenoids, xerophilusins A-C (1-3), together with a known one, macrocalin B (4), were isolated from the leaves of Isodon xerophilus. Their structures were elucidated on the basis of their spectral properties and X-ray crystallographic analysis. Compounds 1, 2, and 4 showed significant cytotoxic activity against K562, HL-60, and MKN-28 cells.

Antineoplastic Agents, Phytogenic↗
PubMed2000

[The regulating mechanism of anti-fungicides on mouse oocyte development].

AIM: To study the mechanism of the effect of gonadotropin-induced oocyte maturation. METHODS: Mouse oocytes were cultured in HX-medium, and the effects of amphotericin B and ketoconazole on resumption of meiosis of mouse oocyte were examined. RESULTS: 1. FSH(10-200 IU/L) induced a dose-dependent manner of oocytes maturation in CEO. A maximum increase in GVBD was observed with 25-50 IU/L FSH. 2. Amphotericin tericim B (0.025-2.5 micrograms/L) caused significant increases in GVBD in CEO, which mimicked the function of FSH. 3. Ketoconazole (10(-7)-10(-3) mol/L) inhibited the effect of FSH on resumption of meiosis, but no effect on oocyte spontaneous maturation. CONCLUSION: Amphotericin B and ketoconazole are able to affect mouse oocyte maturation, and indicates that they have a regulation on FSH-induced synthesis of meiosis-activating sterol.

Amphotericin B↗
PubMed1999

An amino acid change in the exodomain of the E2 protein of Sindbis virus, which impairs the release of virus from chicken cells but not from mosquito cells.

In order to obtain a mutant of Sindbis virus (SV) with a low methionine-resistant (LMR) phenotype, i.e., able to replicate in methionine-deprived Aedes albopictus mosquito cells, standard SV (SV(STD)) was passaged 17 times in mosquito cells maintained in a low methionine medium and then plaque-purified, also in mosquito cells. Although the virus obtained by this procedure, SV(LM17), did have the desired LMR phenotype, it also appeared to have acquired a host-range phenotype. We have now characterized the host-range phenotype of SV(LM17) in greater detail. In yield assays, the titer of SV(LM17) produced by chick embryo fibroblasts (CEF) was 100- to 1000-fold lower than that from mosquito cells. SV(STD), in contrast, produced a similar titer of virus from the two cell types. On the other hand, when SV(LM17) was assayed directly by plaque formation on CEF and on mosquito cell monolayers, no host restriction in CEF was observed. When CEF were infected with SV(LM17), viral proteins were synthesized normally, pE2 was processed to E2, and E2 was demonstrated by the fluorescent antibody method to reach the cell surface. However, electron microscopy of SV(LM17)-infected cells revealed an absence of extracellular virions and of budding particles; also, nucleocapsids were not aligned beneath the plasma membrane. By sequence determination and by site-directed mutagenesis, it was determined that the host restriction of SV(LM17) was due to a change from Ala to Val at position 251 of the E2 protein. Substitution of Gly or Leu at this position also resulted in the same host range phenotype.

Aedes↗