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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

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

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

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

[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

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

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

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

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

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

Reduction of GTP activation of adenylate cyclase system by its coupling to hormone receptor.

We have examined the characteristics of the adenylate cyclase system from control and butyrate-treated cells. Butyrate treatment results in both an increased number of catecholamine receptors and an induction of a response to the hormone, as reported previously (Tallman, J.F., Smith, C.C., and Henneberry, R.C. (1977) Proc. Natl. Acad. Sci. U.S.A. 74, 873-877); in addition, we found that the same treatment reduces the degree of activation of adenylate cyclase by GTP. We have demonstrated in two cell types that this decrease in GTP activation is inversely related to the degree of induction of the hormone response. Furthermore, in plasma membranes isolated from butyrate-treated cells, the hormone receptor is sensitive to GTP; i.e. GTP reduces the affinity of isoproterenol for the receptor. We propose that these changes reflect an interaction between the beta-adrenergic receptor and the nucleotide regulatory component and that this interaction represents, at least in part, the process of coupling. Several possible mechanisms which can account for the change in GTP activation are discussed in terms of our current understanding of the regulation of the adenylate cyclase system.

1-Methyl-3-isobutylxanthine

Routine amnioscopy at term.

A controlled study for the management of antepartum meconium-stained amniotic fluid (MSAF) detected by amnioscopy performed in a total of 508 patients is presented. The incidence of antepartum MSAF was 2.2%, while intrapartum MSAF was found in 15% of cases. A significant incidence of depressed neonates was found in the latter group. Patients with antepartum MSAF had no perinatal losses, whether managed expectantly or by oxytocin induction. Immediate operative intervention (ie, cesarean section) is not warranted. Observations on FHR patterns, fetal pH, and Apgar scores of these patients are presented.

Apgar Score

Electron microscopy of albumin synthesis.

Albumin molecules appeared to be synthesized in the light hepatocytes of rats by bound polysomers on rough and endoplasmic reticulum and the nuclear envelope. The molecules were discharged directly into the cytosol, then to the external cellular spaces. This conclusion failed to support the current theory from biochemical studies that albumin is synthesized by bound ribosomes, discharged into the cisternae of rough endoplasmic reticulum, and transported to the smooth endoplasmic reticulum and then to the Golgi apparatus. In addition to the liver, positive syntheic activities were observed in the aorta, kidney, and hepatoma cells of rat. Earlier investigators have reported that only liver cells can synthesize albumin.

Albumins

An empirical method of grouping genotypes based on a linear function of the genotype-environment interaction.

The regression approach for analysing genotype-environmental interaction is extended to include the grouping of genotypes. An unweighted pair-group cluster analysis was applied to a special dissimilarly index, derived from the test statistic for differences among regressions. The resulting groups reflect the general pattern of response to the various environments. The data of Yates and Cochran (1938) were used to illustrate the clustering process.

Environment

Calcitonin inhibition of bone cell metabolism in vivo: an experimental study in dogs.

Calcitonin (CT) has been shown to act by decreasing the output of calcium from the bone, but the precise mechanism that brings about this change is still not fully understood. The present investigation was designed to study the effect of CT on the metablic activity of bone cells, utilizing changes in oxygen consumption and carbon dioxide production as indices of tissue metabolism. Arterio-venous gradients of calcium, inorganic phosphate, hydroxyproline, oxygen, carbon dioxide and hydrogen ions were studied across the canine femur. The results showed that the hypocalcemic action of CT was accompanied by a corresponding decrease in free hydroxyproline output from the bone, demonstrating that decreased bone resorption was responsible for the fall in plasma calcium levels. Reduced oxygen consumption and decreased carbon dioxide production by the bone showed that CT acted by inhibiting the metabolic activity of bone cells in vivo. It is speculated that CT may have acted by depressing mitochondrial respiration.

Animals