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Biomedical subjects

L Liu

Publications and source records attributed to L Liu.

At least 1,153 records · Page 64Linked to original sources

Immunological studies on the pathogenesis of pterygium.

Immunohistochemical, electron microscopic and routine pathological studies were conducted to observe the changes in T-cell subsets, B-cells, plasma cells, and mast cells, and the distributions of immunoglobulins (IgE, IgG, IgA, IgM) and C3 in patients with pterygium. The results were as follows. Massive amounts of infiltrating lymphocytes, predominantly T-cells (CD3+), were found in the substantia propria of the pterygial specimens. The helper-suppressor ratio had risen from 1:2.7 in the normal conjunctiva to 1:1.5. Positive cytoplasmic immunoglobulin staining indicated a plasmocytic infiltration in the lesions as well. Abnormal distributions of immunoglobulins were found, and deposition of immunoglobulins in a granular pattern around the basement membrane of the epithelial layer was seen. Mast cell reactions were found, and a linear correlation between the numbers of lymphocytes and mast cells was shown. Basement membrane destruction in the cap area of the pterygium was also confirmed. These results indicate that an immunologic mechanism, possibly of Types 1, 3 and 4 hypersensitivity, may contribute to the pathogenesis of pterygium.

Basement Membrane↗

[Effects of ethanol and norepinephrine injected into nucleus hypoglossus on the genioglossal muscle activities].

Integrated genioglossal and phrenic muscle activities were recorded on 87 urethane anesthetized, vagotomized rabbits to study the effect of ethanol and norepinephrine (NA) injected into nucleus hypoglossus on the potentiating effects of integrated genioglossal and phrenic muscle activities (PIMA). It was found that ethanol could inhibit PIMA of genioglossal muscle. Peak amplitude of PIMA (PAMP) was reduced with the latency of PIMA (LAT) prolonged and recovery time (RT) shortened. Norepinephrine facilitated PIMA, which could be blocked by Tolazolin. Local administration of ethanol (2 mol/L 1 microliter) to the caudal part of the 4th ventricle floor produced statistically significant reduction in genioglossal muscle activities (P < 0.01) in resting respiration. The present results suggest that ethanol exerts inhibitory effect on genioglossal muscle activity which may be associated with the inhibition of nucleus hypoglossus per se or caudal part of the 4th ventricle floor. The excitatory activity of genioglossal muscle may be mediated by noradrenergic receptors in the nucleus hypoglossus.

Animals↗

[Modulating effects of nucleus termination nervi trigemini on the activities of genioglossus in rabbits].

The effects of electrical stimulation to the nucleus termination nervi trigemini (NTV) on the activities of genioglossus were studied in 35 rabbits anesthetized with urethane. Electrical stimulation of NTV could cause facilitatory response of genioglossal muscle markedly. Monosodium glutamate microinjected into NTV also produced significant increase of genioglossal activities. The latency of genioglossal response to electrical stimulation of dorsal or ventral part of NTV were respectively 5.9 +/- 0.7 ms and 3.0 +/- 0.4 ms. When the nucleus hypoglossus was stimulated, the latency was 2.2 +/- 0.2 ms. These results suggested that the excitation of NTV could enhance the genioglossal activities so that the resistance of upper airway might be decreased.

Animals↗

Cloning and sequencing of a human cDNA from cytolytic NK/T cells with homology to yeast SEC7.

Using the technique of subtractive hybridization (natural killer (NK) minus T helper cell line Jurkat), a human cDNA clone named B2-1 was isolated and sequenced. B2-1 transcripts are highly expressed in NK and peripheral T cells, but not in the T helper cell line used in the subtraction. Two overlapping cDNA clones contained 3309 bp, in agreement with a predicted size of 3.2 kb obtained by Northern blot analysis. The cDNA contained a 5' open reading frame encoding a 398 amino acid (aa) protein with a calculated M(r) of 46,383. The protein contains N-linked glycosylation sites and a site for phosphorylation by protein kinase C. Database homology searches show that the deduced protein is novel and has three discrete domains with significant homology to several structural proteins. The most striking homology was to yeast SEC7 in the central domain of the gene (57% identical over 466 bp) and also the protein level (42% identical amino acids; 39% conserved amino acids). SEC7 is a large protein (2008 amino acids) found on Golgi vesicles that plays a role in protein transport.

Amino Acid Sequence↗

Progress in establishing the rate-limiting features and kinetic mechanism of the glyceraldehyde-3-phosphate dehydrogenase reaction.

Primary hydrogen isotope effects and steady-state kinetics have been used to study the mechanism of glyceraldehyde-3-phosphate (GAP) dehydrogenase at pH 8.6. The isotope effect determined by using GAP-1d was unity and independent of arsenate (used as the acyl acceptor) and NAD+ concentrations when the aldehyde substrate was at saturating concentrations. At low GAP concentrations (apparent V/K conditions), the primary hydrogen isotope effect (H/D) was in the range of 1.40-1.52 and independent of arsenate and NAD+ concentrations. Apparent V/K for NAD+ was independent of GAP concentration, and apparent V/K for GAP was independent of NAD+ concentration. The dependence of apparent V/K for GAP on arsenate concentration was more complex but extrapolated to nonzero V/K at the zero-arsenate intercept. These observations are consistent with the general features of the Segal and Boyer (1953) mechanism for the reaction.

Arsenates↗

Mutation of asparagine 229 to aspartate in thymidylate synthase converts the enzyme to a deoxycytidylate methylase.

The conserved Asn 229 of thymidylate synthase (TS) forms a cyclic hydrogen bond network with the 3-NH and 4-O of the nucleotide substrate dUMP. The Asn 229 to Asp mutant of Lactobacillus casei thymidylate synthase (TS N229D) has been prepared, purified, and investigated. Steady-state kinetic parameters of TS N229D show 3.5- and 10-fold increases in the Km values of CH2H4folate and dUMP, respectively, and a 1000-fold decrease in kcat. Most important, the Asp 229 mutation changes the substrate specificity of TS to an enzyme which recognizes and methylates dCMP in preference to dUMP. With TS N229D the Km for dCMP is bout 3-fold higher than for dUMP, and the Km for CH2H4folate is increased about 5-fold; however, the kcat for dCMP methylation is 120-fold higher than that for dUMP methylation. Specificity for dCMP versus dUMP, as measured by kcat/Km, changes from negligible with wild-type TS to about a 40-fold increase with TS N229D. TS N229D reacts with CH2H4folate and FdUMP or FdCMP to form ternary complexes which are analogous to the TS-FdUMP-CH2H4folate complex. From what is known of the mechanism and structure of TS, the dramatic change in substrate specificity of TS N229D is proposed to involve a hydrogen bond network between Asp 229 and the 3-N and 4-NH2 of the cytosine heterocycle, causing protonation of the 3-N and stabilization of a reactive imino tautomer. A similar mechanism is proposed for related enzymes which catalyze one-carbon transfers to cytosine heterocycles.

Amino Acid Sequence↗

Polar zipper sequence in the high-affinity hemoglobin of Ascaris suum: amino acid sequence and structural interpretation.

The extracellular hemoglobin of Ascaris has an extremely high oxygen affinity (P50 = 0.004 mmHg). It consists of eight identical subunits of molecular weight 40,600. Their sequence, determined by protein chemistry, shows two tandemly linked globin-like sequences and an 18-residue C-terminal extension. Two N-linked glycosylation sites contain equal ratios of mannose/glucosamine/fucose of 3:2:1. Electron micrographs suggest that the eight subunits form a polyhedron of point symmetry D4, or 42. The C-terminal extension contains a repeat of the sequence Glu-Glu-His-Lys, which would form a pattern of alternate glutamate and histidine side chains on one side and of glutamate and lysine side chains on the other side of a beta strand. We propose that this represents a polar zipper sequence and that the C-terminal extensions are joined in an eight-stranded beta barrel at the center of the molecule, with histidine and glutamate side chains inside and lysine and glutamate side chains outside the barrel compensating each other's charges. The amino acid sequence of Ascaris hemoglobin fails to explain its high oxygen affinity.

Amino Acid Sequence↗

Synthesis and in vitro evaluation of boronated uridine and glucose derivatives for boron neutron capture therapy.

The following boron-containing nucleoside and glucose derivatives have been synthesized as potential boron delivery agents for boron neutron capture therapy (BNCT): 2'-O-(o-carboran-1-ylmethyl)uridine (4a), 3'-O-(o-carboran-1-ylmethyl)uridine (4b), sodium 7-(uridin-2'-ylmethyl)dodecahydro-7,8-dicarba-++ +nido-undecaborate (5), 5'-O-(o-carboran-1-ylmethyl)uridine (9), and 3'-O-(o-carboran-1-ylmethyl)-D-glucose (13). In vitro cellular uptake studies were performed with F98 rat glioma cells. Following 16 h incubation, cellular boron concentrations were determined by direct current plasma atomic emission spectroscopy (DCP-AES). Boron concentrations ranged from 65 to 103 micrograms/g of cells for the neutral closo structures compared with 1.5 micrograms/g of cells for the charged nido species. Cellular uptake of sodium mercaptoundecahydro-closo-dodecaborate (BSH), the compound currently being used in Japan for the treatment of malignant brain tumors by BNCT, was 2 micrograms/g of cells.

Animals↗

The m gamma delta-1 element, a small gamma delta (Tn1000) derivative useful for plasmid mutagenesis, allele replacement and DNA sequencing.

Transposon gamma delta (Tn1000), a 6-kb member of the Tn3 family, is widely used for plasmid mutagenesis. A 1.8-kb derivative of gamma delta was constructed that contains the kan gene from Tn5 and the resolution (res) site from gamma delta cloned between 40-bp inverted repeats of gamma delta's delta (delta) end. This element, named m gamma delta-1, lacks the genes encoding transposase and resolvase, and therefore depends on its host to supply transposition and resolution functions. Thus, in strains lacking gamma delta, m gamma delta-1 will not transpose. The m gamma delta-1 element is shown to be useful for mutagenesis of plasmids, DNA sequencing, and allele replacement (in Streptomyces avermitilis).

Alleles↗

Loss of NF1 alleles in phaeochromocytomas from patients with type I neurofibromatosis.

Type I neurofibromatosis (NF1) is a common autosomal dominant disorder that affects tissues derived from the neural crest. The manifestations are varied, comprising generalised disorders of growth and development as well as an increased risk of benign and malignant tumours including phaeochromocytomas and neurofibrosarcomas. The NF1 locus has been mapped to chromosome bands 17q11-12, and recently the NF1 gene has been cloned. Deletions identified in the constitutional genotype of some patients have suggested that the NF1 phenotype may arise from loss of function mutations of the NF1 gene, consistent with the hypothesis that it is a tumour suppressor gene. To date, however, analysis of NF1 tumours has not revealed the frequent allele losses encompassing the NF1 locus, implying loss of the wild-type NF1 allele, which would support this hypothesis. We report allele losses with markers flanking the NF1 region in each of 7 NF1 phaeochromocytomas. In each of the 3 tumours for which this could be determined, the loss involved the wild-type chromosome. These results provide strong evidence that, in cells of the adrenal medulla at least, the NFI gene may act as a tumour suppressor.

Adrenal Gland Neoplasms↗

Insulin-like growth factor binding protein (IGFBP-3), an inhibitor of serum growth factors other than IGF-I and -II.

Our results show that an insulin-like growth factor binding protein, IGFBP-3, purified from rat serum, is an inhibitor of chick embryo fibroblast (CEF) growth. It abolished DNA synthesis in CEF stimulated by IGF-I as well as by human serum. Rat IGFBP-3 and IDF45 (an inhibitory diffusible factor secreted by mouse cells) had the same activities, confirming that they have an intrinsic capacity to inhibit serum stimulation and may be considered as growth inhibitors. Our data show that inhibition by IGFBP-3 of serum stimulation was not simply the result of its inhibition of IGF present in the serum: 1) While anti-IGF-I IgG was able to completely inhibit stimulation induced by added IGF-I, it did not decrease stimulation induced by 1% human serum. Anti-IGF-II IgG inhibited the stimulation induced by added IGF-II, but only 25% decreased the stimulation induced by 0.7% serum. The percent inhibition was not significantly increased when the concentration of serum was decreased to 0.2%, which induced 140% stimulation of DNA synthesis; 2) stimulation by 0.2% serum was much more inhibited by IGFBP-3 than by IgG anti IGF-II; 3) after separation of IGF-I and IGF-II from serum by chromatography of acidified serum proteins on BioGel P150, the remaining serum proteins (with a molecular mass greater than 45 kDa) which were depleted in IGF-I and -II (verified by RIA determination) still stimulated DNA synthesis, and this stimulation was 80% inhibited by IGFBP-3.

Animals↗

Takayasu arteritis in China: a report of 530 cases.

A total of 530 patients with Takayasu arteritis were studied. Among 346 patients who were diagnosed by aortography, the female to male ratio was 2.9 to 1, and the age of onset ranged from 5 to 45 years. Three hundred and eighteen (60%) patients with secondary hypertension, including renovascular hypertension in 281, and 197 (37.2%) with pulseless extremities were found in the series. All the patients were treated with medical or surgical procedures. Surgical treatment is preferred if clinical status of the patient permits. The patients were followed for 1-29 years (average 7.8 years). There were 55 deaths (10.4%) in this series. Cerebral hemorrhage was found as a common cause of death. Five-year and ten-year survival rates were 93.1% and 91.1%, respectively.

Adolescent↗

The relationship between intracardiovascular smoke-like echo and erythrocyte rouleaux formation.

Intravascular smoke-like echo always appears in regions of stasis, but the exact mechanism of its production is unclear. We investigated its appearance in relation to erythrocyte rouleaux formation. To study this relationship we performed a series of in vitro and animal experiments. In the in vitro study, we observed an erythrocyte suspension by ultrasonography and found it to be echo-free. Under the microscope, red blood cells were observed in a dispersed state. If an equal amount of lymphocyte separation solution was added to the suspension, smoke-like echo appeared, and red blood cells were seen in a rouleaux pattern. In animal (mongrel dogs) experiments, under physiologic conditions with normal blood flow velocity, all cardiac cavities and the inferior vena cava were echo-free. When stasis was induced experimentally in the inferior vena cava, red blood cells aggregated to form rouleaux and smoke-like echo appeared. On resumption of normal blood flow, the rouleaux dispersed to form erythrocytes again. The mechanism of production of intracardiovascular smoke-like echo is closely related to the formation of erythrocyte rouleaux. When rouleaux are formed, they become larger and appear nearer or larger than the ultrasonic wavelength. Thus reflections are produced and smoke-like echo appears.

Animals↗