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Biomedical subjects

J Lin

Publications and source records attributed to J Lin.

At least 235 records · Page 13Linked to original sources
PubMed1998

[The effect of amlodipine, nifedipine and perindopril on insulin sensitivity and blood lipid of patients with essential hypertension].

OBJECTIVE: To investigate the effect of amlodipine, nifedipine and perindopril on insulin sensitivity(IS) and blood lipid of patients with essential hypertension(EH). METHODS: 105 EH patients were randomly divided into 3 groups: amlodipine group; nifedipine group; perindopril group. Treatment period lasted for 4 weeks. Before and after treatment, IS was measured by euglycemic insulin clamp technique with glucose metabolism rate (M) as an index of IS. RESULTS: Amlodipine, nifedipine and perindopril significantly reduced blood pressure compared with that before treatment(P < 0.01). In the EH patients with decreased IS, the M value (mg.kg-1.min-1) after the use of amlodipine, nifedipine and perindopril was higer than that before treatment (amlodipine: 6.6 +/- 1.5 Vs 4.6 +/- 0.6, P < 0.01; nifedipine: 5.2 +/- 1.2 Vs 4.4 +/- 0.6, P < 0.05; perindopril: 6.8 +/- 1.6 Vs 4.4 +/- 0.6, P < 0.01). The increase of M value(mg.kg-1.min-1), nifedipine (1.2 +/- 0.9) were significantly lower than that of amlodipine(2.1 +/- 1.1) and perindopril(2.4 +/- 1.5), P < 0.01, respectively, but no significant difference was found between amlodipine and perindopril(P > 0.05). CONCLUSION: Amlodipine and perindopril have beneficial effect on improving insulin sensitivity in EH patients with decreased insulin sensitivity. The effect of nifedipine on insulin sensitivity is lower than that of amlodipine and perindopril. Blood lipid is not significantly changed after short treatment.

Amlodipine↗
PubMed1998

[The effects of BDP on eosinophils in nasal secretions of the patient with allergic rhinilis].

The effects of beclomethasone dipropionate (BDP) on eosinophils in nasal secretions of the patients with allergic rhinilis was assaied under the laser scanning confocal microscopy and the technology of fluoresence. The scanning images displayed that fluoresence signal of the eosinophils intracellular RNA was significantly decreased after BDP treatment. The results showed that anti-inflammation funtion of BDP was realized by controlling the intracellular DNA translate to RNA.

Anti-Inflammatory Agents↗
PubMed1998

[Neurotoxicity of antibody against motoneuron on cultured rat cortical neurons].

OBJECTIVE: In order to determine the role of antibody against motoneuron in the process of neuronal death. METHODS: Cultured rat cortical neurons growing in serum-free medium, were employed to observe the effects of antibody against motoneuron (anti-SMN) on the survival of these cultured neurons. RESULTS: (1) Exposure of the cultures in serum-free medium to anti-SMN with dilution of 1:50 results in death of 31%-41% of neurons for 24 hours incubation, 50%-67% for 48 hours and above 90% after 72 hours. The neurotoxicity induced by anti-SMN was accompanied by concentration-dependent release of lactate dehydrogenase into the culture medium. Cultures exposed to normal rat IgG as controls exhibited no such sign. (2) The cultured neurons exposed to anti-SMN (1:200) expressed markedly higher levels of immunoreactive Calbindin-D28k especially after 48 hours incubation with it. There was a reduction in the number of acetylcholinesterase-positive neurons compared to the normal control. CONCLUSIONS: The anti-SMN could directly initiate the process of cortical neuronal death and this effect was independent of complement. The alteration of Calbindin-D28k immunoreactivity implied that calcium may be involved in the neurotoxicity induced by anti-SMN.

Acetylcholinesterase↗
PubMed1998

[The general survey for chondromalacia of 2,743 Chinese population].

OBJECTIVE: To evaluate the distribution of chondromalacia patella in Chinese population. METHODS: A random cluster sampling survey was performed covering 2,743 subjects varied in age, sex and occupation in 1995. RESULTS: The prevalence rate is 36.2%. The occurrence in women was higher than that in men (P < 0.01), while in the age group, 30 to 39 years was the highest being 55.8%. The prevalence rate in soldier being 47.5% was the highest among varied occupations. CONCLUSIONS: Our study is the first survey to be performed in a large number of Chinese population. This investigation may reflect the prevalence rate of chondromalacia patella in China.

Adolescent↗
PubMed1998

[Expression of IL-1 mRNA and its correlation with astrocytes and NOS-positive neurons in rat spinal cord following sciatic nerve injury].

OBJECTIVE: To study expression of Interleukin 1 (IL-1) and its correlation with astrocytes and nitric-oxide synthase (NOS)-positive neurons in rat spinal cord following sciatic nerve transection. METHODS: Using RT-PCR and immunohistochemistry methods. RESULTS: The experiments showed that IL-1 expression appeared with a low frequency at 3 days after the axontomy, while it could be markedly detectable on post-lesioned day 7 and 14. In normal controls and the spinal fragments without being involved in the injury, no signal of IL-1 mRNA expression was detected with the same condition. At 7 days after nerve injury, the lesioned side of spinal cord began to show strong glial fibrillary acidic protein (GFAP) immunoreactive astrocytes and induction of NOS in the motoneurons that are normally NOS-negative. Up to 21 days after operation, GFAP staining showed star-shaped astrocytes closely resembling the typical appearance of fibrous astrocytes and GFAP-immunoreactive profiles were often seen surrounding NOS-positive neurons. Analysis of the time course of IL-1 mRNA expression, appearance of NOS-positive neurons and changes of reactive astrocytes suggested a close relationship between them. CONCLUSIONS: IL-1, NO might function as important mediators between injured motoneurons and astrocytes.

Animals↗
PubMed1998

Pulsatile insulin release: role of cytoplasmic Ca2+ oscillations.

Oscillations of plasma insulin are essential for the hypoglycaemic effect of the hormone. Disturbance and partial loss of these oscillations occur during the development of Type 2 diabetes, in association with down-regulation of insulin receptors and insulin resistance. Oscillations with a frequency similar to that of plasma insulin have been observed in the cytoplasmic Ca2+ concentration ([Ca2+]i) of pancreatic beta cells, indicating that the ion plays a role in generating insulin pulses. Studies of individual islets have revealed that oscillations of [Ca2+]i and insulin release are synchronous. However, insulin release is also pulsatile under conditions in which [Ca2+]i is stable. These results support the notion that variations in the ATP/ADP ratio are sufficient to induce pulsatile insulin release. Under physiological conditions, this pulsatility may depend on the synergistic effects of ATP/ADP and [Ca2+]i oscillations.

Animals↗
PubMed1998

Biomechanical comparison of antegrade and retrograde nailing of humeral shaft fracture.

A pair-controlled study was conducted to compare biomechanical properties of antegrade and retrograde nailing of humeral fractures. First, six paired fresh anatomic specimen humeri were used to compare the properties of humeri fractured at the middle to distal diaphyses junction that were nailed from the retrograde approach with the Humeral Locked nail with those of contralateral intact humeri. An 18 additional pairs were divided into three equal groups by distal, proximal, or mid-diaphysis location of a standardized 5-mm bone defect to simulate unstable fractures. The retrograde and antegrade nailings were performed in each pair in a random manner. Nail and bone constructs were tested for bending stiffness by nondestructive three-point bending and for torsional stiffness by destructive torsional tests. Compared with intact humeri, fractured humeri fixed with nails had 28.6% posteroanterior and 31.4% mediolateral bending stiffness, 22.5% torsional stiffness, and 43.3% failure torque. For distal fractures, retrograde nailing showed significantly more initial stability and higher bending and torsional stiffness; for proximal fractures, antegrade nailing showed similar properties. For middle to distal diaphyses junction fractures, retrograde and antegrade nailing were indistinguishable. The defect created as an entry portal for retrograde nailing reduced the bone strength only 11.1%. These results suggest that retrograde nailing, which is less detrimental to shoulder function than is antegrade nailing, is an acceptable alternative treatment for humeral shaft fractures. In addition, nailing from the short to the long bone segments can improve mechanical properties of the fixation construct because of better nail and bone interface purchase.

Biomechanical Phenomena↗
PubMed1998

Neurochemical and behavioral effects of ciproxifan, a potent histamine H3-receptor antagonist.

Ciproxifan, i.e., cyclopropyl-(4-(3-1H-imidazol-4-yl)propyloxy) phenyl) ketone, belongs to a novel chemical series of histamine H3-receptor antagonists. In vitro, it behaved as a competitive antagonist at the H3 autoreceptor controlling [3H]histamine release from synaptosomes and displayed similar Ki values (0.5-1.9 nM) at the H3 receptor controlling the electrically-induced contraction of guinea pig ileum or at the brain H3 receptor labeled with [125I]iodoproxyfan. Ciproxifan displayed at least 3-orders of magnitude lower potency at various aminergic receptors studied in functional or binding tests. In vivo, measurement of drug plasma levels, using a novel radioreceptor assay in mice receiving ciproxifan p.o. or i.v., led to an oral bioavailability ratio of 62%. Oral administration of ciproxifan to mice enhanced by approximately 100% histamine turnover rate and steady state level of tele-methylhistamine with an ED50 of 0.14 mg/kg. Ciproxifan reversed the H3-receptor agonist induced enhancement of water consumption in rats with and ID50 of 0.09 +/- 0.04 mg/kg, i.p. In cats, ciproxifan (0.15-2 mg/kg, p.o.) induced marked signs of neocortical electroencephalogram activation manifested by enhanced fast-rhythms density and an almost total waking state. In rats, ciproxifan enhanced attention as evaluated in the five-choice task performed using a short stimulus duration. Ciproxifan appears to be an orally bioavailable, extremely potent and selective H3-receptor antagonist whose vigilance- and attention-promoting effects are promising for therapeutic applications in aging disorders.

Animals↗
PubMed1998

Primary ureteral carcinoma. Report of 15 cases and comparison of the effectiveness of diagnostic methods.

Fifteen cases of primary urothelial carcinomas of the ureter are reported (14 transitional cell carcinoma and 1 mixed transitional cell carcinoma and squamous cell carcinoma). There was a clear male predominance (11/4); the peak incidence was in the sixth decade. Most tumors originated from the distal third of the ureter. Multicentricity and high recurrence rate after partial ureterectomy were noted. The clinical signs were hematuria and flank pain. Urine cytology and IVU were diagnostic in a limited number of cases. Retrograde pyelography was very helpful. CT showed to be the image modality of choice for diagnosis and preoperative staging.

Aged↗
PubMed1997

Kinase-independent potentiation of B cell antigen receptor-mediated signal transduction by the protein tyrosine kinase Src.

Signal transduction mediated by the B cell Ag receptor involves the activation of multiple protein tyrosine kinases that are members of the Src family (i.e., Fyn, Lyn, Blk, Lck). To determine whether members of the Src family possess common physical and/or enzymatic properties that enable them to potentiate signal transduction via the B cell Ag receptor, we expressed the protein tyrosine kinase Src in the B lymphoma cell line K46-17 mu m lambda. Based on coprecipitation analysis and two-color immunofluorescence, this heterologous Src family kinase was observed to physically associate with the B cell Ag receptor. Additional experiments demonstrated that B cell Ag receptor cross-linking results in increased tyrosine phosphorylation and activation of Src. Several parameters of B cell activation, including tyrosine phosphorylation of intracellular substrates, calcium mobilization, and transcription factor activation, were potentiated in cells that expressed Src when compared with control cells. To determine whether potentiation of Ag receptor-mediated signaling by Src was dependent on its catalytic activity, a kinase-deficient form of Src was expressed in K46-17 mu m lambda cells. Transfectants expressing kinase-deficient Src exhibited an enhanced responsiveness to stimulation through the B cell Ag receptor that was comparable with transfectants expressing wild-type Src. Additionally, kinase-deficient Src was observed to associate with the endogenous kinase Lyn in an activation-dependent manner. These findings indicate that members of the Src family may potentiate Ag receptor-mediated signaling via a kinase-independent mechanism(s) that involves amplification of kinase recruitment to the Ag receptor activation complex.

Adjuvants, Immunologic↗
PubMed1997

Genomic structures of cardiotoxin 4 and cobrotoxin from Naja naja atra (Taiwan cobra).

Two genomic DNAs with the size of 2.3 kb and 2.4 kb, which were isolated from the liver of Naja naja atra (Taiwan cobra), encoded the precursors of cardiotoxin 4 and cobrotoxin, respectively. Both genes shared virtually identical overall organization with three exons separated by two introns, which were inserted in the similar positions of the gene's coding regions. Moreover, their nucleotide sequences shared approximately 84.2% identity. This result reveals the evolutionary relationship between cardiotoxin and cobrotoxin. The exon/intron structures of cardiotoxin 4 and cobrotoxin genes were similar to that reported for erabutoxin c gene, a neurotoxin genomic DNA from a sea snake (Laticauda semifasciata). However, in contrast to the finding that the intron 2 of these genes had a similar size, a notable variation with the size of intron 1 was observed (1233 bp, 1269 bp and 197 bp for cardiotoxin 4, cobrotoxin and erabutoxin c genes, respectively). The different size with intron 1 is due to the middle region at the first intron of cardiotoxin 4 and cobrotoxin genes, which encoded small nucleolar RNA (snoRNA), being absent in that of erabutoxin c gene. These results, together with the finding of the potential mobility of snoRNA genes during evolution, suggest that intron insertions or deletions of snoRNA genes occur with the evolutionary divergence of snake neurotoxins and cardiotoxins.

Amino Acid Sequence↗
PubMed1997

Both lumenal and cytosolic gating of the aqueous ER translocon pore are regulated from inside the ribosome during membrane protein integration.

Portions of the nascent chain are exposed to the lumen, the cytosol, or neither at different stages during the cotranslational integration of a protein into the ER membrane, as shown by compartment-specific collisional quenching of fluorophores incorporated into the polypeptide. The opening or closing of each end of the aqueous translocon pore is tightly controlled and occurs in a sequence that does not compromise the membrane's permeability barrier. Surprisingly, these structural changes at the membrane are effected by the transmembrane segment in the nascent protein from inside the ribosome. Thus, the ribosome, not the translocon, first recognizes the transmembrane segment and triggers long-range structural changes at the translocon that may be involved in shifting its function from translocation to integration.

Animals↗
PubMed1997

A new concept for the mechanism of action of chymotrypsin: the role of the low-barrier hydrogen bond.

The basicities of the diad H57-D102 at N(epsilon)2 in the tetrahedral complexes of chymotrypsin with the peptidyl trifluoromethyl ketones (TFK) N-acetyl-L-Leu-DL-Phe-CF3 and N-acetyl-DL-Phe-CF3 have been studied by 1H-NMR. The protons bridging His 57 and Asp 102 in these complexes are engaged in low-barrier hydrogen bonds (LBHBs). In 1H-NMR spectra at pH 7.0, these protons appear at delta 18.9 and 18.6 ppm, and the pK(a)s of the diads are 12.0 +/- 0.2 and 10.8 +/- 0.1, respectively. The difference indicates that removal of leucine from the second aminoacyl site S2 of chymotrypsin weakens the LBHB and decreases the basicity of the H57-D102 diad relative to the case in which S2 is occupied by leucine. Consideration of the available structural data on chymotrypsin and other serine proteases, together with the high pK(a)s of the hemiketals formed with TFKs, suggests that LBHB formation in catalysis arises through a substrate-induced conformational transition leading to steric compression between His 57 and Asp 102. Because the N-O distance in the LBHB is shorter than the Van der Waals contact distance, the LBHB is proposed to stabilize the tetrahedral intermediate through relief of steric strain between these residues. In this mechanism, substrate-induced steric compression within the diad increases the basicity of N(epsilon)2 in His 57, making it a more effective base for abstracting a proton from Ser 195 in the formation of the tetrahedral intermediate. The values of pK(a) for N(epsilon)2 in TFK adducts lie between those of Ser 195 (pK(a) approximately 14) and the leaving group in tetrahedral adducts (pK(a) approximately 9), making N(epsilon)2 of the H57-D102 diad strong enough as a base to abstract the proton from Ser 195 in tetrahedral adduct formation but not so strong that its conjugate acid cannot protonate the leaving group. According to this theory, the "normal" pK(a) of His 57 in free chymotrypsin arises from the use of part of the stabilization energy provided by the LBHB to drive the conformational compression required for its formation. In catalysis, the energy for conformational compression is supplied by the binding of remote portions of the substrate, including the side chains of P1 and P2.

Animals↗
PubMed1997

Solution structure of the quaternary MutT-M2+-AMPCPP-M2+ complex and mechanism of its pyrophosphohydrolase action.

The MutT enzyme (129 residues) catalyzes the hydrolysis of nucleoside triphosphates (NTP) by substitution at the rarely attacked beta-P, to yield NMP and pyrophosphate. It requires two divalent cations, forming an active E-M2+-NTP-M2+ complex. The solution structure of the free enzyme consists of a five-stranded mixed beta-sheet connected by loop I-alpha-helix I-loop II, by two tight turns, and by loop III and terminated by loop IV-alpha-helix II [Abeygunawardana, C., et al. (1995) Biochemistry 34, 14997-15005]. Assignments of backbone 15N and NH resonances and side chain 15N and NH2 resonances of the quaternary complex were made by 1H-15N HSQC titrations of the free enzyme with MgCl2 followed by equimolar AMPCPP/MgCl2. H(alpha) assignments were made by 1H-15N 3D TOCSY HSQC, and 1H-13C CT-HSQC spectra and backbone and side chain 1H and 13C assignments were made by 3D HCCH TOCSY experiments. Ligands donated by the protein to the enzyme-bound divalent cation, identified by paramagnetic effects of Co2+ and Mn2+ on CO(C)H spectra, are the carboxylate groups of Glu-56, -57, and -98 and the amide carbonyl of Gly-38. The solution structure of the complex was computed with XPLOR using a total of 2168 NOE and 83 phi restraints for the protein, 11 intramolecular NOEs for bound Mg2+ AMPCPP, 22 intermolecular NOEs between MutT and AMPCPP, and distances from the enzyme-bound Co2+ to the three phosphorus atoms of Co3+(NH3)4AMPCPP from paramagnetic effects of Co2+ on their T1 values. The fold of the MutT enzyme in the complex is very similar to that of the free enzyme, with minor changes in the metal and substrate binding sites. The adenine ring binds in a hydrophobic cleft, interacting with Leu-4 and Ile-6 on beta-strand A and with Ile-80 on beta-strand D. The 6-NH2 group of adenine approaches the side chain NH2 of Asn-119. This unfavorable interaction is consistent with the stronger binding by MutT of guanine nucleotides, which have a 6-keto group. The ribose binds with its hydroxyl groups oriented toward the solvent and its hydrophobic face interacting with Leu-4, Ile-6, and the gamma-CH2 of Lys-39 of loop I. The metal-triphosphate moiety appears to bind in the second coordination sphere of the enzyme-bound divalent cation. One of two intervening water ligands is well positioned to attack P(beta) with inversion and to donate a hydrogen bond to the conserved residue, Glu-53, which may deprotonate or orient the attacking water ligand. Lys-39 which is positioned to interact electrostatically with the alpha-phosphoryl group may facilitate the departure of the leaving NMP. On the basis of the structure of the quaternary complex, a mechanism of the MutT reaction is proposed which is qualitatively and quantitatively consistent with kinetic and mutagenesis studies. It is suggested that similar mechanisms may be operative for other enzymes that catalyze substitution at P(beta) of NTP substrates.

Adenosine Triphosphate↗
PubMed1997

Competitive binding of alpha-actinin and calmodulin to the NMDA receptor.

The mechanisms by which neurotransmitter receptors are immobilized at postsynaptic sites in neurons are largely unknown. The activity of NMDA (N-methyl-D-aspartate) receptors is mechanosensitive and dependent on the integrity of actin, suggesting a functionally important interaction between NMDA receptors and the postsynaptic cytoskeleton. alpha-Actinin-2, a member of the spectrin/dystrophin family of actin-binding proteins, is identified here as a brain postsynaptic density protein that colocalizes in dendritic spines with NMDA receptors and the putative NMDA receptor-clustering molecule PSD-95. alpha-Actinin-2 binds by its central rod domain to the cytoplasmic tail of both NR1 and NR2B subunits of the NMDA receptor, and can be immunoprecipitated with NMDA receptors and PSD-95 from rat brain. Intriguingly, NR1-alpha-actinin binding is directly antagonized by Ca2+/calmodulin. Thus alpha-actinin may play a role in both the localization of NMDA receptors and their modulation by Ca2+.

Actins↗
PubMed1997

Human hepatic microsomal epoxide hydrolase: comparative analysis of polymorphic expression.

Interindividual variation in the expression of human microsomal epoxide hydrolase (mEH) may be an important risk factor for chemically induced toxicities, including cancer and teratogenesis. In this study, phenotypic variability and mEH genetic polymorphisms were examined in a bank of 40 transplant-quality human liver samples. Immunochemically determined protein content, enzymatic activities, polymorphic amino acids, as well as mEH RNA levels were evaluated in parallel. Enzymatic activity was assessed using (+/-)-benzo[a]pyrene-4,5-epoxide at 2 substrate concentrations. The relative hydrolyzing activities obtained using saturating substrate levels were highly correlated (r = 0.85) with results derived from limiting substrate concentrations and exhibit approximately an 8-fold range in activity levels across the panel of 40 liver samples. mEH enzyme activity also demonstrated strong correlation (r > or = 0.74) with an 8.4-fold variation determined for mEH protein content within the same samples. However, these protein/activity measurements were poorly correlated (r < or = 0.23) with mEH RNA levels, which exhibited a 49-fold variation. Two common polymorphic amino acid loci in the mEH protein did not exclusively account for variation in enzymatic activity, although this conclusion is confounded by heterozygousity in the samples. These data demonstrate the extent of hepatic mEH functional variability in well-preserved human tissues and suggest that polymorphism of mEH protein expression is regulated in part by posttranscriptional controls, which may include nonstructural regulatory regions of the mEH transcript.

Adolescent↗