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Biomedical subjects

C Lin

Publications and source records attributed to C Lin.

At least 37 records · Page 2Linked to original sources
PubMed1991

Diffusion of water in biological tissues.

A method is presented for obtaining simple approximate solutions for the problem of self-diffusion in an ordered array of obstacles. Our results are compared with some previous exact and approximate solutions, and we find that our method agrees well with the exact results over a large range of the volume fraction of the obstructions. It is shown that there is an important distinction between measurements of the diffusion coefficient by the capillary flow method and the spin-echo method. The modifications for the spin-echo case are given and applied to recent measurements on the anisotropy of the self-diffusion of water in striated muscle and to measurements on cysts of the brine shrimp. The analysis shows that very large volume fractions of obstructive barriers are required in order to account for the reduction in the diffusion coefficient in biological systems. Thus this model analysis leads to the supposition that a substantial fraction (20-40%) of the cell water is hydration water, or that the diffusion coefficient of the cytoplasmic water is reduced substantially from the free water value. In either case, the conclusion that a substantial fraction of cell water has diffusive properties that are altered by the macromolecules of the cytoplasm seems inescapable. In the case of NMR methodology, the measuring times are such that the values for diffusion are often influenced by the presence of macromolecular structures (obstructions) within the cells. This suggests that obstructions make a significant contribution to the value of the NMR diffusion coefficient and that NMR may have practical value for the evaluation of obstruction effects.

Animals↗
PubMed1991

Defined physical limits of the Huntington disease gene candidate region.

The Huntington disease (HD) gene has been mapped 4 cM distal to D4S10 within the telomeric chromosome band, 4p16.3. The published physical map of this region extends from D4S10 to the telomere but contains two gaps of unknown size. Recombination events have been used to position the HD mutation with respect to genetic markers within this region, and one such event places the gene proximal to D4S168, excluding the distal gap as a possible location for the defect. One previously published recombination event appeared to have excluded the proximal gap. We have reassessed this event and have moved the proximal boundary for the HD candidate region centromeric to the gap within a "hot spot" for recombination between D4S10 and D4S125. We have closed the proximal gap and report here the complete physical map spanning the HD candidate region from D4S10 to D4S168, the maximum size of which can now be placed accurately at 2.5 Mb.

Chromosome Mapping↗
PubMed1990

Expression in yeast of the T-urf13 protein from Texas male-sterile maize mitochondria confers sensitivity to methomyl and to Texas-cytoplasm-specific fungal toxins.

The mitochondrial gene T-urf13 from maize (Zea mays L.) with Texas male-sterile (T) cytoplasm codes for a unique 13 kd polypeptide, T-URF13, which is implicated in cytoplasmic male sterility and sensitivity to the insecticide methomyl and to host-specific fungal toxins produced by Helminthosporium maydis race T (HmT toxin) and Phyllosticta maydis (Pm toxin). A chimeric gene coding for T-URF13 fused to the mitochondrial targeting peptide from the Neurospora crassa ATP synthase subunit 9 precursor was constructed. Expression of this gene in the yeast Saccharomyces cerevisiae yielded a polypeptide that was translocated into the membrane fraction of mitochondria and processed to give a protein the same size as maize T-URF13. Methomyl, HmT toxin and Pm toxin inhibited growth of yeast cells expressing the gene fusion on medium containing glycerol as sole carbon source and stimulated respiration with NADH as substrate by isolated mitochondria from these cells. These effects were not observed in yeast cells expressing T-URF13 without a targeting peptide. The results show that T-URF13 is sufficient to confer sensitivity to methomyl and the fungal toxins in a heterologous eukaryotic system, and suggest that mitochondrial localization of T-URF13 is critical for these functions.

Amino Acid Sequence↗
PubMed1990

[Facilitation of arginine-vasopressin analogs on learning and memory in rats].

Adult rats were trained in a maze for brightness discrimination (BD) or in a shuttle box for active avoidance. It was found that the pretreatment of 1-desamino-8-D-arginine-vasopressin (DDAVP) enhanced the retention of brightness discrimination and retarted the extinction of avoidance response. Neonatal daily administration for 14 d of both 9-desglycylamide-DDAVP (DGDDAVP) or 2-destyrosyl-3-desphenylalanyl-9-desglycylamide-AVP (AVP4-8), but not D-arginine-AVP4-8 (DAVP4-8) showed significant facilitation on acquisition and subsequent maintenance of BD in adult rats. The results indicate that some of synthetic arginine-vasopressin analogs may directly act on CNS and consequently affect learning behaviors in rats.

Animals↗
PubMed1990

Angiotensin binding sites in rabbit anterior uvea and human ciliary epithelial cells.

Angiotensin binding sites in membrane homogenates of rabbit iris/ciliary body and human nonpigmented ciliary epithelial (NPE) cells grown in culture were characterized using radioligand binding assays with (125I)-sarcosine1-isoleucine8-angiotensin II [(125I)-SARILE]. Scatchard analysis of the binding of (125I)-SARILE yielded linear plots with a Kd value of 0.55 +/- 0.1 nM and a Bmax of 98 +/- 23 fmol/mg protein in rabbit iris/ciliary body, and a Kd value of 0.63 +/- 0.1 nM, and a Bmax of 36.2 +/- 24 fmol/mg protein in NPE cells. Studies of the inhibition of the binding of (125I)-SARILE in rabbit iris/ciliary body were performed with a series of competing ligands, including the angiotensin receptor antagonist SARILE and the agonists angiotensin I, angiotensin II and angiotensin III. Inhibition curves for the antagonist resulted in Hill coefficients of approximately 1, consistent with the presence of a single class of binding sites with high affinity for (125I)-SARILE. Competition for the binding of (125I)-SARILE to binding sites with each of the agonists resulted in inhibition curves with Hill coefficients significantly less than 1 in the absence of GTP. However, in the presence of 100 microM GTP the Hill coefficients increased to approximately 1. The order of potencies of these agents was consistent with the pharmacologic profile of angiotensin II receptors. Thus rabbit iris/ciliary body homogenates, which include vascular tissue, contain a homogeneous population of angiotensin binding sites coupled to a guanine nucleotide binding protein. The presence of binding sites in cultured NPE cells indicates that at least some are located on the cells thought to be responsible for aqueous humor secretion.

Angiotensin I↗
PubMed1989

Structural changes at the myogenic cell surface during the formation of myotendinous junctions.

Myotendinous junctions are sites which are morphologically and molecularly specialized for force transmission between intracellular and extracellular structural proteins. In the present investigation, the formation of these specialized junctions is studied in chicken embryos from 9 days following fertilization to 1 day posthatching, using light and electron microscopy. Observations indicate that the first discernible event in myotendinous junction formation is the appearance of basement membrane at the incipient junction at 9-10 days postfertilization, concomitant with the aggregation of fibroblasts at the junctional regions of myogenic cells. Subsequently, subsarcolemmal densities appear at sites opposite basement membrane locations by 13 days postfertilization. Myofibrils insert into subsarcolemmal densities by day 15 and invaginations of the cell membrane are initiated at those insertions. Type I collagen fibers appear at the cell surface at day 17. Junctional structure at day 17 qualitatively resembles that of adult myotendinous junctions. Changes in junctional structure following day 17 are primarily increases in the amount of subsarcolemmal densities, myofibril-membrane associations, and amount of junctional membrane folding.

Animals↗
PubMed1989

Pharmacokinetics and tissue penetration of Sch 39304 in granulocytopenic and nongranulocytopenic rabbits.

We studied the plasma pharmacokinetics and tissue penetration of Sch 39304 (SCH), a new antifungal triazole, in granulocytopenic [G(+)] and nongranulocytopenic [G(-)] rabbits. Five female New Zealand White G(-) rabbits were given a single oral dose of 2 mg of SCH per kg of body weight. Levels in plasma, determined by gas-liquid chromatography-electron capture, were obtained for 6 days. This procedure was repeated 2 weeks later with the same rabbits, which were induced and maintained G(+) with cytosine arabinoside. There were no significant differences between the pharmacokinetic parameters of G(+) and G(-) rabbits. Among all animals studied, the maximum concentration of the drug in plasma was 1.4 +/- 0.11 micrograms/ml at 4 +/- 0.5 h, the half-life was 25 +/- 1.4 h, the volume of distribution at steady state was 3.8 +/- 0.3 liters, and the area under the concentration-time curve was 44 +/- 3.4 micrograms.h/ml. SCH was detectable in plasma up to day 6. Levels of SCH in tissue were studied at steady state in six G(+) and six G(-) rabbits receiving 2 mg of the drug orally per kg per day for experimental disseminated candidiasis. Tissue SCH levels equalled or exceeded those in plasma (at steady state) at all sites examined, and these ratios were similar in both G(+) and G(-) rabbits. Thus, plasma pharmacokinetics of orally administered SCH were similar for G(+) and G(-) rabbits, and SCH achieved high levels of penetration into multiple tissues, including the liver and the central nervous system.

Agranulocytosis↗
PubMed1989

Landau-Kleffner syndrome with unilateral EEG abnormalities--two cases from Beijing, China.

We reported 2 cases of Landau-Kleffner syndrome from Beijing whose clinical manifestations were very similar to ones previously reported. The onset of symptoms in these 2 cases was at 3 and 4 years of age, respectively, and both were characterised by unilateral focal epileptiform EEG discharges, without remarkable clinical seizures. One patient had normal SPECT study in addition to normal CT scan, BAER and VER results; the other had a family history of epilepsy. Since this syndrome may involve a primary brain disturbance responsible for both the epilepsy and aphasia without clear structural brain lesions, we wonder whether it can be classified as one of the benign functional partial epilepsies with genetic factors.

Aphasia↗
PubMed1987

Activity of (+)-cyclaradine (Sch 31172) against herpes simplex virus in vitro and in vivo.

(+)-Cyclaradine (Sch 31172) is the carbocyclic derivative of adenosine arabinoside (9-beta-D-arabinofuranosyladenine). Because it is not deaminated by deaminase in serum, as is adenosine arabinoside, (+)-cyclaradine is about 2 to 5 times more active in vitro against herpes simplex virus. (+)-Cyclaradine has in vitro activity nearly equivalent to that of phosphonoformate but is significantly less active than acycloguanosine (acyclovir; ACV), trifluorothymidine, or 9-(1,3-dihydroxy-2-propoxymethyl)guanine. The absolute ratios of in vitro activities are difficult to determine because of variability among virus strains, inoculum size, and dependence on the tissue culture cell line in which the comparative test is carried out. (+)-Cyclaradine is active against TK-, ACV-resistant mutants. In the guinea pig model of vaginal herpes simplex virus infection, (+)-cyclaradine is only slightly less active than ACV when both molecules are nearly equivalently bioavailable; thus, the large difference in activity seen in vitro is not reflected in this in vivo model system.

Acyclovir↗
PubMed1987

Characterization of D-2 dopamine receptors in a tumor of the rat anterior pituitary gland.

Dopamine receptors in the 7315a transplantable rat anterior pituitary tumor were characterized using radioligand binding assays with [3H]spiroperidol ([3H]SPD) and assays of adenylate cyclase activity. Scatchard analysis of the binding of [3H]SPD yielded linear plots and a Kd value of 73 pM. Studies of the inhibition of the binding of [3H]SPD were performed with a series of competing ligands, including the antagonists domperidone, (+)-butaclamol and sulpiride and the agonists dopamine, bromocriptine and N-propylnorapomorphine. Inhibition curves for the antagonists gave Hill coefficients of approximately 1, consistent with the presence of only a single class of binding sites with a high affinity for [3H]SPD. In contrast, the Hill coefficient for dopamine was significantly less than 1. When assays were carried out in the presence of 300 microM GTP, the inhibition curve for dopamine was shifted to the right and the Hill coefficient increased to approximately 1. An effect of GTP on the affinity of a receptor for agonists is consistent with the existence of at least two agonist affinity states. Inhibition of the binding of [3H]SPD by the partial agonist bromocriptine was not affected when assays were carried out in the presence of GTP. The uniform low affinity of the selective serotonin antagonist ketanserin for these sites indicated that the radioligand was not labeling serotonin-2 receptors in this tissue. A good correlation was observed between the Ki values for competing ligands measured in the tumor and in homogenates of rat striatal tissue. Dopamine was shown to inhibit forskolin-stimulated adenylate cyclase activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclase Inhibitors↗
PubMed1985

Relationship between production of epidermal growth factor receptors, gene amplification, and chromosome 7 translocation in variant A431 cells.

Synthesis of the epidermal growth factor (EGF) receptor has been analyzed in a series of variant A431 human epidermoid carcinoma cell clones reported to contain different amounts of EGF binding sites. The amount of EGF receptor protein, quantitated by immunoaffinity chromatography, and EGF receptor mRNA, quantitated by cDNA hybridization, were closely correlated to the extent of EGF receptor gene amplification. This correlation existed in variants selected for reduced EGF receptors and in revertants from those variants with increased EGF receptors. There was also a correlation between the frequency of translocation of chromosome 7, containing the EGF receptor gene, and EGF receptor protein. These results support gene amplification as the mechanism enhancing A431 cell EGF receptor protein and determining growth responses.

Carcinoma, Squamous Cell↗