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Biomedical subjects

M Lin

Publications and source records attributed to M Lin.

At least 217 records · Page 12Linked to original sources

Long-term potentiation and depression in layer III and V pyramidal neurons of the cat sensorimotor cortex in vitro.

Synaptic plasticity of the cat sensorimotor cortex was examined intracellularly in vitro. After tetanic stimulation of the white matter, layer III and V pyramidal neurons showed long-term potentiation (LTP) of EPSPs in high incidence without GABA(A) antagonist. The incidence and magnitude of LTP were very conspicuous in layer V cells. After an NMDA receptor antagonist application, the synaptic potentiation was blocked completely in layer III but not in layer V cells. Long-term depression (LTD) of the evoked EPSPs was also induced by the same stimulation in some layer III cells, where a transient hyperpolarization of the membrane potential was observed during tetanus.

2-Amino-5-phosphonovalerate↗

The genomic structure of a mouse seminal vesicle autoantigen.

The genomic structure of an androgen-stimulated mouse seminal vesicle autoantigen was determined. Analysis of the nucleotide sequence established 2135 bp of the 5'-flanking region, four exons of 123, 136, 112, 227 bp, three introns of 1555, 1931, 316 bp, and 185 bp of the 3'-flanking region of this gene. Ten DNA segments, five in the 5'-flanking region, two in the first intron, and three in the second intron were identified to have more than 50% homology with the consensus sequence of the androgen response element (ARE). Two sets of adjacent DNA segments, one including -213 to -199 bp and -124 to -110 bp in the 5'-flanking region and the other including 2532 to 2546 bp and 2582 to 2596 bp in the second intron, are noticeable for their high degree of homology with ARE.

Androgens↗

Binding of the Brucella abortus lipopolysaccharide O-chain fragment to a monoclonal antibody. Quantitative analysis by fluorescence quenching and polarization.

An antigenic O-chain polysaccharide fragment derived from Brucella abortus lipopolysaccharide was labeled with 14.8 +/- 1.8 (n = 5) and 52.3 +/- 2.4 (n = 3) micromol of fluorescein/g of polysaccharide (designated FL1 and FL2, respectively) for use in investigating the binding of O-chain to a specific murine antibody YsT9 under equilibrium conditions. Upon binding to YsT9, the fluorescence of FL1 and FL2 was quenched 45-57% with no shift in the excitation and emission spectra, and polarization of fluorescence increased by 300-335%. With fluorescence quenching and polarization as sensitive signals for antibody-bound labeled O-chains, the equilibrium constants for binding of FL1, FL2, and unlabeled O-chain to YsT9 were determined to be within a similar order (1.5 x 10(7) to 2.0 x 10(7) M-1) using a nonlinear curve fitting approach rather than Scatchard analysis. These results indicated that covalent attachment of fluorescein groups to the O-chain did not influence the recognition of the YsT9-defined epitope by the antibody. The reversibility of the O-chain-antibody reaction was also demonstrated by showing a rapid depolarization of the labeled O-chain-antibody complex in the presence of unlabeled O-chain, suggesting that this displacement experiment could be exploited to quantify the Brucella polysaccharide antigen. The study described here provides a useful model for characterization of the complex formation between a carbohydrate-binding protein and a carbohydrate ligand and also for the design of a homogeneous assay system to quantitate antigens or antibodies of clinical interest.

Animals↗

Control of G1 in the developing Drosophila eye: rca1 regulates Cyclin A.

In the developing eye of Drosophila melanogaster, cells become synchronized in the G1 phase of the cell cycle just prior to the onset of cellular differentiation and morphogenesis. In roughex (rux) mutants, cells enter S phase precociously because of ectopic activation of a Cyclin A/Cdk complex in early G1. This leads to defects in cell fate and pattern formation, and results in abnormalities in the morphology of the adult eye. A screen for dominant suppressors of the rux eye phenotype led to the identification of mutations in cyclin A, string (cdc25), and new cell cycle genes. One of these genes, regulator of cyclin A (rca1), encodes a novel protein required for both mitotic and meiotic cell cycle progression. rca1 mutants arrest in G2 of embryonic cell cycle 16 with a phenotype very similar to cyclin A loss of function mutants. Expression of rca1 transgenes in G1 or in postmitotic neurons promotes Cyclin A protein accumulation and drives cells into S phase in a Cyclin A-dependent fashion.

Amino Acid Sequence↗

Effects of exposure to carbon disulfide (CS2) on electrocardiographic features of ischemic heart disease among viscose rayon factory workers.

The objective of the study was to evaluate viscose plant workers for electrocardiographic manifestations resulting from exposure to carbon disulfide (CS2). A total of 162 workers (118 in an exposure group and 44 in a reference group) were evaluated using a health questionnaire, physical check-up, biochemical analysis of blood samples and electrocardiograms (ECG). The exposure group consisted of workers in the following areas: viscose manufacturing, cellophane processing, ripening, and filament spinning. Reference group workers were from the administrative office, rolling area, pulp processing, and testing office. Only slight differences were found in the biochemical analyses of the two groups, with the exception of sodium (Na) levels. Personal and area sampling results were found to have a high variation due to different locations within the plant and a wide range of manufacturing processes. Highest CS2 concentrations were found in the ripening area (54.60 ppm) and the filament spinning area (19.60 ppm). Using a multiple logistic regression model to control variables (age, gender, body mass index, duration of employment, cholesterol, smoking, and alcohol), we found a relative risk for ECG abnormalities 4.18 times significantly higher for the exposure group. The authors feel that the installation of an adequate ventilation system could greatly reduce the risk of workers developing CS2-induced cardiovascular abnormalities.

Adult↗

Delta-opiate DPDPE in magnetically oriented phospholipid micelles: binding and arrangement of aromatic pharmacophores.

D-Penicillamine(2,5)-enkephalin (DPDPE) is a potent opioid peptide that exhibits a high selectivity for the delta-opiate receptors. This zwitterionic peptide has been shown, by pulsed-field gradient 1H NMR diffusion studies, to have significant affinity for a zwitterionic phospholipid bilayer. The bilayer lipid is in the form of micelles composed of dihexanoylphosphatidylcholine (DHPC) and dimyristoylphosphatidylcholine (DMPC) mixtures, where the DMPC forms the bilayer structure. At high lipid concentration (25% w/w) these micelles orient in the magnetic field of an NMR spectrometer. The resulting 1H-13C dipolar couplings and chemical shift changes in the natural abundance 13C resonances for the Tyr and Phe aromatic rings were used to characterize the orientations in the bilayer micelles of these two key pharmacophores.

Biophysical Phenomena↗

A mechanistic study of griseofulvin dissolution into surfactant solutions under laminar flow conditions.

The in vivo dissolution of many poorly soluble drugs is enhanced by the action of surfactants secreted into the upper gastrointestinal (GI) tract. These substances may act by solubilizing individual drug molecules into two separate liquid phases: the free aqueous phase and a micellar phase in which the drug is incorporated into a complex of two or more surfactant molecules. This complex process, micellar solubilization, was the subject of this in vitro study, wherein griseofulvin (gris) dissolution was observed in flowing surfactant solutions. Aqueous solutions of sodium dodecyl sulfate (SDS), an anionic surfactant, were pumped over a gris tablet embedded in a laminar flow device to simulate flow in the human upper GI tract. SDS solutions were well above the critical micellar concentration (cmc approximately 6-7 mM), and flow rates ranged from 4 to 7 mL/min. Gris solubility in premicellar (4 mM), near-micellar (6 mM), and micellar (>6 mM) SDS solutions was also determined. The measured solubility of gris increased linearly with SDS concentrations above the cmc. Drug solubility in SDS concentrations below the cmc was also higher than that in water. Gris diffusion coefficients were measured using pulsed-field gradient NMR spectroscopy. To determine the controlling mechanism for surfactant-enhanced dissolution, a mathematical model was developed. The model solution, an equation for drug dissolution rate, was compared with experimental data to demonstrate that drug transport away from the solid surface is the slow step in the process. Measured gris diffusion coefficients and solubility values were used as constants in the mathematical model solution and were combined to calculate an effective gris diffusion coefficient. Using these experimentally determined properties, model-calculated dissolution rates were within 7% of the measured values. As hypothesized, dissolution rates were found to be directly proportional to the transport properties of the system (effective drug diffusion coefficient and fluid flow rate) as well as to the drug solubility. To further verify transport-limited dissolution, the measured dissolution rates were found to be proportional to the surrounding medium flow rate to the 1/3 power, as predicted by the model dissolution rate equation.

Antifungal Agents↗

Heterogeneity of the human H blood group alpha(1,2)fucosyltransferase gene among para-Bombay individuals.

BACKGROUND AND OBJECTIVES: The para-Bombay phenotype has a relatively high frequency of about 1 in 8,000 Taiwanese. Studies were carried out on eight healthy and unrelated Taiwanese with the para-Bombay phenotype to cast light on its immunogenetic basis. MATERIALS AND METHODS: Blood and saliva samples were tested with standard hemagglutination techniques. Salivary ABH substances were determined by hemagglutination inhibition. PCR techniques were used to amplify the coding region of the H genes. RESULTS: Five different h alleles, designated as h1, h2, h3, h4 and h5, were identified in the Taiwanese with the para-Bombay phenotype. The h1 allele loses one of the three AG repeats located at the nucleotides 547-552 of the H gene, whereas two of the three T repeats located at the nucleotides 880-882 are deleted in the h2 allele. The h3 allele contains a C658 to T missense mutation, whereas two missense mutations, C35 to T and A980 to C were identified in the h4 allele. A T460 to C missense is present in the h5 allele. The h5 allele was identified in an individual whose red blood cells contain blood group A antigen but not H antigen, and thus may be considered a weak variant of the H gene. CONCLUSIONS: So far no biologic relevance of the H antigen has been discovered, and its deficiency does not seem to produce any deleterious effects. There may be better understanding of the evolutionary basis for the polymorphisms at these loci after systematic study of different ethnic populations.

ABO Blood-Group System↗

Posttesticular development of spermatozoa of the tammar wallaby (Macropus eugenii).

Tammar wallaby spermatozoa undergo maturation during transit through the epididymis. This maturation differs from that seen in eutherian mammals because in addition to biochemical and functional maturation there are also major changes in morphology, in particular formation of the condensed acrosome and reorientation of the sperm head and tail. Of spermatozoa released from the testes, 83% had a large immature acrosome. By the time spermatozoa reached the proximal cauda epididymis 100% of sperm had condensed acrosomes. Similarly 86% of testicular spermatozoa had immature thumb tack or T shape head-tail orientation while only 2% retained this immature morphology in the corpus epididymis. This maturation is very similar to that reported for the common brush tail possum, Trichosurus vulpecula. However, morphological maturation occurred earlier in epididymal transit in the tammar wallaby. By the time spermatozoa had reached the proximal cauda epididymis no spermatozoa had an immature acrosome and thumbtack orientation. Associated with acrosomal maturation was an increase in acrosomal thiols and the formation of disulphides which presumably account for the unusual stability of the wallaby sperm acrosome. The development of motility and progressive motility of tammar wallaby spermatozoa is similar to that of other marsupials and eutherian mammals. Spermatozoa are immotile in the testes and the percentage of motile spermatozoa and the strength of their motility increases during epididymal transit. During passage through the caput and corpus epididymis, spermatozoa first became weakly motile in the proximal caput and then increasingly progressively motile through the corpus epididymis. Tammar wallaby spermatozoa collected from the proximal cauda epididymis had motility not different from ejaculated spermatozoa. Ultrastructural studies indicated that acrosomal condensation involved a complex infolding of the immature acrosome. At spermiation the acrosome of tammar wallaby spermatozoa was a relatively large flat or concave disc which projected laterally and anteriorly beyond the limits of the nucleus. During transit of the epididymal caput and proximal corpus the lateral projections folded inwards to form a cup like structure the sides of which eventually met and fused. The cavity produced by this fusion was lost as the acrosome condensed to its mature form as a small button-like structure contained within the depression on the anterior end of the nucleus. During this process the dorsal surface of the immature acrosome and its outer acrosomal membrane and overlying plasma membrane were engulfed into the acrosomal matrix. This means that the dorsal surface of the acrosomal region of the testicular tammar wallaby sperm head is a transient structure. The dorsal acrosomal surface of the mature spermatozoon appears ultrastructurally to be the relocated ventral surface of the acrosomal projections which previously extended out beyond the acrosomal depression on the dorsal surface of the nucleus of the immature spermatozoon.

Acrosome↗

Spermiogenesis and spermiation in a marsupial, the tammar wallaby (Macropus eugenii).

Fourteen steps of spermatid development in the tammar wallaby (Macropus eugenii), from the newly formed spermatid to the release of the spermatozoon into the lumen of the seminiferous tubules, were recognised at the ultrastructural level using transmission and scanning electron microscopy. This study confirmed that although the main events are generally similar, the process of the differentiation of the spermatid in marsupials is notably different and relatively more complex than that in most studied eutherian mammals and birds. For example, the sperm head rotated twice in the late stage of spermiogenesis: the shape of the spermatid changed from a T-shape at step 10 into a streamlined shape in step 14, and then back to T-shape in the testicular spermatozoa. Some unique figures occurring during the spermiogenesis in other marsupial species, such as the presence of Sertoli cell spurs, the nuclear ring and the subacrosomal space, were also found in the tammar wallaby. However, an important new finding of this study was the development of the postacrosome complex (PAC), a special structure that was first evident as a line of electron dense material on the nuclear membrane of the step 7 spermatid. Subsequently it became a discontinuous line of electron particles, and migrated from the ventral side of the nucleus to the area just behind the posterior end of the acrosome, which was closely located to the sperm-egg fusion site proposed for Monodelphis domestica (Taggart et al. 1993). The PAC and its possible role in both American and Australian marsupials requires detailed examination. Distinct immature features were discovered in the wallaby testicular spermatozoa. A scoop shape of the acrosome was found on the testicular spermatozoa of the tammar wallaby, which was completely different to the compact button shape of acrosome in ejaculated spermatozoa. The fibre network found beneath the cytoplasm membrane of the midpiece of the ejaculated sperm also did not occur in the testicular spermatozoa, although the structure of the principle piece was fully formed and had no obvious morphological difference from that of the epididymal and ejaculated spermatozoa. The time frame of the formation of morphologically mature spermatozoa in the epididymis of the tammar wallaby needs to be determined by further studies.

Acrosome↗

Two-photon excitation of 4'-hydroxymethyl-4,5',8-trimethylpsoralen.

Psoralens are a class of pharmaceutical agents commonly used to treat several cutaneous disorders. When irradiated with a mode-locked titanium: sapphire (Ti:sapphire) laser tuned to 730 nm, an aqueous solution of 4'-hydroxymethyl-4,5',8-trimethylpsoralen (HMT) emits blue light. The emission spectrum is centered at 452 nm and is identical to that obtained by one-photon excitation with UVA excitation, and its magnitude depends quadratically on the intensity of laser excitation. These results suggest that two-photon excitation occurs to a potentially photochemically active state. To estimate the two-photon absorption cross section, it was first necessary to measure the emission quantum yield of HMT using 365 nm excitation at room temperature that resulted in a value of 0.045 +/- 0.007. The two-photon absorption cross section of HMT at 730 nm is therefore estimated to be 20 x 10(-50) cm4 s (20 Göppert-Mayer). The excited-state photophysics and photochemistry of psoralens suggest potential applications to cutaneous phototherapy in diseases such as psoriasis and dystrophic epidermolysis bullosa.

Aluminum Oxide↗

Identification of a 35-kilodalton serovar-cross-reactive flagellar protein, FlaB, from Leptospira interrogans by N-terminal sequencing, gene cloning, and sequence analysis.

During the screening of antibodies to pathogenic leptospires, a murine monoclonal antibody (designated M138) was found to react with various serovars. An antigen of approximately 35 kDa from Leptospira interrogans serovar pomona, which reacted strongly with M138, was characterized by N-terminal amino acid sequencing and identified as a flagellin, a class B polypeptide subunit (FlaB) of the periplasmic flagella. The gene encoding the FlaB protein, flaB, was amplified from the genomic DNA of several pathogenic serovars by PCR with a single pair of oligonucleotide primers, suggesting that FlaB is highly conserved among these serovars. Cloning and sequence analysis of flaB from serovar pomona revealed that it contains an 849-bp open reading frame with a G + C content of 46.88% which encodes a 283-amino-acid protein with a calculated molecular mass of 31.297 kDa and a predicted pI of 9.065. A sequence comparison of flagellin proteins revealed that the amino acid sequence is most variable in the central portion of the serovar pomona FlaB, which is believed to contain specific sequence information and which may thus be useful in the design of DNA or synthetic peptide probes suitable for the detection of infection with pathogenic leptospires.

Amino Acid Sequence↗

Diminished retinoic acid signaling in hepatic stellate cells in cholestatic liver fibrosis.

Hepatic stellate cells (HSC) participate in liver fibrogenesis via myofibroblastic activation, the extent of which appears to correlate with the loss of cellular vitamin A. The present study has tested a hypothesis that HSC activation is associated with diminished retinoic acid (RA) signaling. Pure HSC were isolated from rats with cholestatic liver fibrosis induced by bile duct ligation (BDL) and sham-operated animals (Sham). Northern blot analysis of HSC RNA from BDL confirmed fibrogenic activation of the cells with enhanced mRNA levels for procollagen-alpha1(I) and transforming growth factor-beta1 (TGF-beta1). Competitive polymerase chain reaction analysis showed selective reductions in the mRNA levels of RA receptor (RAR)-beta and retinoid X receptor (RXR)-alpha to 20 and 17% of the Sham HSC. The mRNA level for cellular retinol binding protein I, a gene with RA responsive element (RARE), was also suppressed by 78% in BDL. The concentrations of all-trans-RA and 9-cis-RA were decreased in HSC from BDL. Nuclear extracts of these cells showed diminished binding activity to the RARE, whereas activity of AP-1, a transcription factor known to be antagonized by RAR and RXR, was enhanced. These results demonstrate diminished RA signaling in HSC from cholestatic liver fibrosis, which appeared to have resulted from RA deficiency and suppressed expression of RAR-beta and RXR-alpha. Furthermore, the reciprocal enhancement of AP-1 activity and coordinately increased expression of an AP-1 responsive gene, TGF-beta1, suggest a permissive role of the diminished RA signaling in promoting AP-1 activity and TGF-beta1 expression.

Animals↗

Role of iron in NF-kappa B activation and cytokine gene expression by rat hepatic macrophages.

A redox-sensitive nuclear factor, NF-kappa B, induces transcription of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in macrophages. The present study has investigated the role of iron in NF-kappa B activation and TNF-alpha and IL-6 expression by rat hepatic macrophages (HM). As an in vivo model, cholestatic liver injury was induced in rats by ligation of the common bile duct (BDL). During the first 2 wk after BDL, there was an increase in the hepatic level of thiobarbituric acid-reactive substances (TBARS) that was accompanied by the appearance of protein-malondialdehyde adducts in the periportal region. This increase was reduced after 3 wk. TNF-alpha and IL-6 mRNA levels in HM from the BDL rats were increased at 1 and 2 wk and attenuated at 3 wk. Gel mobility shift assay of HM nuclear extracts demonstrated the similar temporal pattern of enhanced NF-kappa B binding activity. Treatment of the BDL animals with 1,2-dimethyl-3-hydroxypyrid-4-one (L-1), a lipophilic iron chelator, suppressed the increases in hepatic TBARS by 64%, plasma alanine aminotransferase by 45%, and HM TNF-alpha and IL-6 mRNA by > 84%. Concomitantly, the HM NF-kappa B binding activity was reduced close to the level observed in sham-operated rats. Treatment of cultured HM with L-1 also blocked lipopolysaccharide-stimulated NF-kappa B activation and TNF-alpha and IL-6 expression at mRNA and protein levels. These results demonstrate that the iron chelator effectively blocks NF-kappa B activation and coordinate TNF-alpha and IL-6 gene upregulation by HM in cholestatic liver injury or under in vitro lipopolysaccharide stimulation. These findings support a pivotal role for iron in activation of NF-kappa B and cytokine gene expression by HM in vitro and in vivo.

Animals↗

Carnosine is a novel peptide modulator of intracellular calcium and contractility in cardiac cells.

Myocardial contractile failure is a common cause of morbidity and mortality in patients with ischemic heart disease and systemic inflammatory states such as sepsis. Accumulating evidence indicates that contractile failure is associated with dysregulation of myoplasmic calcium levels. In a search for biochemical causes for contractile dysfunction, we found that the dipeptide carnosine improves cardiac contractility and tested the possibility that carnosine plays a role in the regulation of intracellular calcium. Carnosine increased contractility in a dose-dependent manner (1-10 mM) in isolated perfused rat hearts. and it also increased free intracellular calcium levels in isolated myocytes. Carnosine increased myocyte tension via calcium release from the ryanodine receptor calcium release channel in skinned myocardial fibers and increased open-state probability and dwell time of the isolated ryanodine receptor calcium release channel in lipid bilayers. In addition. we report that carnosine sensitizes the contractile proteins so calcium. These results suggest a novel role for carnosine as a modulator of intracellular calcium and contractility in cardiac tissue.

Animals↗

[The changes of proportion in hospitalized patients with glaucoma].

OBJECTIVE: To investigate the change of proportion of all kinds of hospitalized patients with glaucoma for the prevention and treatment of the disease. METHODS: 3165 cases in our glaucomatous Department from 1990 to 1996 are classified by their diagnosis, sex and age to analyze the changing feature of proportion. RESULTS: 55.86% of the glaucoma are primary angle closed glaucoma (PACG). Most of the primary angle closed glaucoma (PACG) patients are female over 40 years old. The proportion of POAG is 19.25%, glycocorticoid induced glaucoma (GIG), 4.35%. Young male account for the main parts among these cases with GIG. CONCLUSION: The new trends has emerged in glaucoma practice because the very complicated aspects appear in patients, especially in young adults with POAG and GIG of management.

Adolescent↗

[Effect of cyclosporin A on intracellular accumulation and efflux of drug in K562/DOX cells].

OBJECTIVE: To explore measures to overcome multidrug resistance of tumor cells. METHODS: The effects of cyclosporin A (CsA) on drug sensitivity, intracellular drug accumulation and drug efflux in multidrug-resistant human leukemic cell line K562/DOX were studied by MTT colorimetric assay and spectrofluorimetry. RESULTS: CsA enhanced the cytotoxicity of doxorubicin (DOX) to K562/DOX, and when CsA > or = 2microg/ml the sensitivity of K562/DOX to DOX increased significantly. The efflux of DOX markedly decreased when K562/DOX cells were incubated with 2microg/ml CsA, while CsA had no effect on efflux of DOX in K562 cells. CONCLUSION: CsA could markedly decrease the efflux and enhance the intracellular accumulation of DOX in K562/DOX cells.

Cyclosporine↗