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Biomedical subjects

L Lei

Publications and source records attributed to L Lei.

53 records · Page 3Linked to original sources
PubMed1997

Synthesis and evaluation of trimetoquinol derivatives: novel thromboxane A2/prostaglandin H2 antagonists with diminished beta-adrenergic agonist activity.

Trimetoquinol (TMQ, 1) is a unique catecholamine with a strong stereodependence for agonism at beta-adrenergic (S > > R) and antagonism at thromboxane A2/prostaglandin H2 (TP; R > > S) receptors. Our laboratory has reported the effects of N-alkylation and modification of the trisubstituted benzyl group in these receptor systems. For iodinated derivative 5, maintaining potency in TP receptor systems (112%) was coupled with maintaining limited potency in beta-adrenergic receptor systems (34% for beta 1 and 47% for beta 2). In this study, several diverse TMQ derivatives were prepared to probe for binding interactions specific to a particular receptor system. Planar amidine 2, which was designed to explore the importance of TMQ's chiral center, showed a dramatic loss of potency (< 1%) in each receptor system. Likewise, the homologation of a previously described N-benzyl derivative (3) to the N-phenylethyl derivative 4 also showed reduced potency (< 3%) in both receptor systems. However, modification of the trimethoxybenzyl group of TMQ to a 4-hydroxy-3-nitrobenzyl group (7) provided a unique lead for TMQ derivatives with significant potency in TP receptor systems (91%) and reduced potency in beta-adrenergic receptor systems (4% for beta 1 and 19% for beta 2).

Adrenergic beta-Agonists↗
PubMed1996

Medetomidine analogs as alpha 2-adrenergic ligands. 2. Design, synthesis, and biological activity of conformationally restricted naphthalene derivatives of medetomidine.

A new series of naphthalene analogs of medetomidine have been prepared and evaluated for their alpha-adrenergic activities. The methylnaphthyl analog 5a showed significant selectivity for alpha 2-adrenoceptors and behaved as a partial alpha 1-agonist in rat aorta preparations. In contrast, the Z-ethylene analog 8c was alpha 1-selective and behaved as a potent alpha 1-antagonist. Two rigid analogs (6 and 7) exhibited large differences in binding affinities at alpha 1-VS alpha 2-receptors, indicating that the conformational flexibility of 5a is important for the fulfillment of the alpha-adrenergic activities. Molecular modeling studies began with conformational analysis of classical phenethylamines and medetomidine analogs. Superimposition of medetomidine conformations with those of phenethylamines provided a tentative explanation for the alpha 2-adrenergic activity of the new imidazoles. A common binding mode for phenethylamines and imidazoles with alpha 2-adrenoceptors is proposed. Knowledge of the biological properties of the 4-substituted imidazoles, integrated with the information derived from computer-assisted molecular modeling, has provided new insights for the structural and conformational requirements of this class as new adrenergic drugs.

Adrenergic alpha-Agonists↗
PubMed1996

Reappraisal of the inspiratory effect of Bötzinger complex on phrenic nerve discharge.

Experiments were done on 12 urethane-chloralose anaesthetized, vagotomized, paralysed and ventilated cats. The effects of electrical microstimulation at the augmenting expiratory neurons (Aug-e) of Bötzinger complex (Bot.c) were investigated. It was found that long train stimulation (100 Hz, 3-50 microA, 4-6 s) caused intensity-dependent inhibition of phrenic inspiratory discharge. The threshold for complete inhibition was 10 +/- 2 microA (mean +/- S.E.). The expiratory duration showed shortening at low intensity (< 7 microA) and prolongation at higher intensity. Short train stimulation (10 microA, 50 ms) delivered in inspiratory phase produced a two-part transient inhibition of phrenic discharge. The latencies of the first- and second-part inhibition were 4.7 +/- 0.16 ms and 95 +/- 3 ms, respectively. Complete termination of inspiration could be produced by a short train delivered at late inspiration. The results suggest the importance of the Aug-e neurons of Bot.c in determining inspiratory amplitude and respiratory phase duration.

Anesthetics, Intravenous↗
PubMed1996

Middle latency somatosensory evoked potentials: noninvasive source analysis.

The sources of the components of short latency somatosensory evoked potential in humans have been identified using electrical source localization, magnetoencephalography, and electrocorticography, but the sources of the middle latency components are less understood. The purpose of this study was to identify the source of the middle latency component N60 of the electrically elicited somatosensory evoked potential (SEP). Noninvasive equivalent electrical multiple dipole source localization technique (BESA) was used. SEPs were recorded from nine healthy subjects with 30 electrodes placed on the scalp. Median nerve at wrist (bipolar electrode), index, and little fingers (ring electrodes) were successively stimulated with 2.1 Hz frequency. A window of 100 ms was analyzed. Spatiotemporal equivalent electrical dipole models, each consisting of four dipoles, explained the three different SEPs, from median, index, and little fingers, with residual variances below 9%. The sources generating N20, P30, and N60 all appeared to locate in the posterior bank of the central sulcus contralateral to the stimulated hand. The location of the dipole number 2, most active around N20 component, differed between the index and little finger models, suggesting that somatotopic organization of the primary somatosensory area of the digits was demonstrated by these models. A radial source (dipole 4) was most active around 60 ms in all three models, thus explaining the N60 component. The location of this dipole did not suggest somatotopic organization specific to the stimulated finger for the 60 ms component.

Adult↗
PubMed1996

[Study of HPV in oral squamous cell carcinoma].

In order to demonstrate the presence of human papillomavirus (HPV) in oral squamous cell carcinoma (OSCC), we detected HPV 16 and 18 type DNA in OSCC and normal mucosa (NOM) by polymerase chain reaction (PCR), then analysed the PCR products using southern blot hybridization. The study shows that the positive rates of HPV DNA were 47.8% (11/23) in OSCC, including HPV16 in 6 samples, HPV18 in 3 samples and 16, 18 co-infection in 2 samples. In contrast, HPV16 DNA were found to be 20% (2/10) in NOM. The results suggest that HPV may play a role in carcinogenesis of OSCC.

Carcinoma, Squamous Cell↗
PubMed1994

Synthesis and biological activities of a new set of irreversibly acting 2-(4'-isothiocyanatobenzyl)imidazoline analogs in rat thoracic aorta.

IBI [2-(4'-isothiocyanatobenzyl)imidazoline, 3] has been shown to cause slow-onset, long-lasting contractions of rat thoracic aorta through a non-alpha-adrenergic receptor (non-alpha-AR) mediated mechanism. A series of IBI-related anlogs 7-14 and 16 was prepared to determine the structural requirements for the interaction with non-alpha-AR in rat aortic strips. All IBI analogs produced concentration-dependent contractile responses on rat thoracic aorta. Whereas the actions of analogs 7, 14, and 16 were partly mediated by alpha-ARs, the stimulatory activities of the remaining IBI analogs were unaffected by phenoxybenzamine pretreatment, suggesting that a non-alpha-adrenergic mechanism is involved. We have shown that the contractile actions of IBI and analogs 10-13 were not blocked with the imidazoline/guanidinium receptive site (IGRS) ligands idazoxan, cirazoline, or clonidine. However, the calcium channel blockers nifedipine or verapamil shifted the concentration-response curve of IBI and its analogs 10-13 to the right and reduced the maximal contractile responses. The action of IBI on rat thoracic aorta was reduced by the omission of extracellular calcium in the medium. These results suggest that the stimulatory activities of IBI and analogs 10-13 are not related to the activation of alpha-AR or IGRS receptors and are likely coupled to the voltage-dependent Ca2+ channels.

Animals↗
PubMed1994

Importance of codon preference for production of human RAP74 and reconstitution of the RAP30/74 complex.

RAP30 and RAP74 are subunits of RAP30/74 (TFIIF, beta gamma), a general initiation and elongation factor for transcription by RNA polymerase II. Methods were previously published for production of human RAP30 and RAP74 in bacterial cells, using a bacteriophage T7 promoter expression system. The vectors described for production of RAP74 were not very efficient and produced significant quantities of RAP74 amino terminal fragments. To improve these vectors, a segment of the human RAP74 cDNA was recoded using a preferred set of codons for translation in Escherichia coli. Recoding dramatically improved protein production and suppressed production of amino-terminal fragments. Improved vectors are reported that produce RAP74 with an LEHHHHHH carboxy-terminal extension (RAP74-H6), for purification on a Ni(2+)-affinity column, and also with the native carboxy terminus (RAP74). Methods for purification of RAP74-H6 and RAP74 are reported. Using these improved vectors, approximately 30 mg of soluble and active RAP74-H6 or RAP74 can be produced and purified from 1 liter of E. coli culture, representing a 10-fold improvement in protein production. Methods have also been developed for reconstitution of native RAP30/74 complex using recombinant proteins. This complex has indistinguishable activity from human RAP30/74 for accurate transcription in vitro.

Amino Acid Sequence↗
PubMed1994

[Preparation of membrane proteins of Trichinella spiralis larva and application of them in detection with ELISA].

Membrane proteins of muscle larva of Trichinella spiralis (T.s) were isolated by using the non-ionic detergent Triton X-114. At least fourteen components in the membrane proteins were separated with SDS-PAGE and then silver nitrate stain. The bands of them were located between 99-18kd MW level. The MW of chief bands were 94, 90, 47, 32 and 28kd. The sensitivity and specificity of these proteins were determined with ELISA. They didn't cross react with sera of rabbits infected with Toxocara canis (T. c), Schistosoma japonicum (S. j), Paragonimus skr jabini (P. s) and Clonorchis sinensis (C. s). Their sensitivity is the same as and their specificity is higher than those of ES antigens and cuticular antigens obtained with cetultrimethylamonium bromide (CTAB) from muscle larva of Trichinella spiralis.

Animals↗
PubMed1993

[Electroacupuncture promotes the regeneration of different fibers in rat's tibial nerve].

METHODS: 45 rats (150-200g) were divided into 9 groups. The experimental steps as follows: (1) injured left tibial nerve (group 1-8) and sham operation (group 9); (2) three days after operation, group 1, 3, 5 and 7 were stimulated with electro-acupuncture (EA) in Huantiao (+) and Sanyinjiao (-); (3) according to different survival time (group 1, 2/10 days, group 3, 4/15 days, group 5, 6/20 days, group 7, 8, 9/25 days), 48h before sacrifice, the left femoral nerve was cut, HRP was injected into the hypodermis of paw pad and gastrocnemius; (4) observe HRP labelled cells in the lumber sympathetic ganglia, ganglion spinale (L4-6) and cornu ventrale of spinal cord (L3-S3). RESULTS: EA 7 days, 2-5 labeled cells were only found in ganglion spinales of group 1; EA for 12 days, the more HRP labeled cells were observed in the lumber sympathetic ganglions (mean = 2.6), ganglion spinales (mean = 4.8) and cornu ventrale (mean = 6) of group 3 as compared with group 4 (P < 0.05); 25 days after operation, the quantity of labeled cells in group 8 was close to group 9. CONCLUSION: (1) EA promote the regeneration of three or more kinds of fibers in tibial nerve; (2) The regeneration velocity of sensory fibers was faster than sympathetic and somatic efferent fibers.

Animals↗
PubMed1993

[A clinicopathological and immunohistochemical study of 49 cases of necrotizing lymphadenitis].

A clinicopathological and immunohistiochemical study of 49 cases of necrotizing lymphadenitis was made. Twenty-four patients were male and twenty-five female with the M:F ratio of 0.96:1. The patients ranged in age from 9 to 62 years with a mean of 26. Forty-nine patients had superficial lymphadenopathy, and twenty-two were accompanied by fever. The results also showed that there was multifoci necrosis present in the involved lymph nodes, particularly in the cortex or/and paracortex, with variable numbers of small lymphocytes, immunoblasts, histocytes and phagocytes, the latter with phagocytized nuclear debris derived from necrotizing T lymphocytes. However, granulocytes and plasmacytes were generally absent, and B lymphocytes rare. The pathogenesis of this disease remains unknown and the pathogen has not been found by Gram, Giemsa, PAS, Ziehl-Neelsen and Warthin-Starry stain. The diagnosis, differential diagnosis and etiology of this disease are discussed. We support the suggestion that this entity be called "Kikuchi-Fujimoto's disease" rather than "Histiocytic necrotizing lymphadenitis".

Adolescent↗
PubMed1992

[Research on serotonergic neurons in lateral raphe nucleus of rat with intracellular injection HRP technique].

UNLABELLED: This experiment was carried out on 35 rats with stereotaxic apparatus following a new coordinate which was designed by ourselves. The microelectrode was pushed into the lateral dorsal raphe nucleus (LDR) under direct vision. The neurons with regular rhythm and slow firing rate were searched by intracellular recording, then the singular cell in LDR was filled with HRP by intracellular iontophoresis. RESULTS: 7 HRP labelling neurons with serotoninergic firing characteristics were observed in LDR. The labelling dendrites were found in neighboured structure (periaqueductal gray, laterodorsal tegmental nucleus, dorsal tegmental nucleus, 4th ventricle). This work demonstrated that LDR plays some role in acupuncture analgesia.

Action Potentials↗
PubMed1989

Studies on the inspiratory generating effect of the dorso-medial area of nucleus facialis.

The responses in phrenic nerve activity resulting from stimulation and successive focal block of the dorso-medial area of nucleus facialis (dmNF) were studied in urethane anaesthetized rabbits. It was found that: (1) Long train stimulation (0.025-0.2 mA, 100 Hz) delivered to the dmNF caused marked prolongation in inspiratory duration and distinct increase in amplitude of phrenic discharge. Continuous inspiration with increased amplitude was usually observed during stimulation. (2) Short train stimulation (10 pulses, 100 Hz, 0.025-0.2 mA) during inspiration increased the duration and amplitude of inspiration. When the short train stimulation was delivered during expiration, inspiration would be initiated prematurely. (3) Microinjection of L-glutamate (0.5 M, 0.5-2 microliters) into the dmNF also increased inspiratory duration and amplitude. (4) Focal block of the dmNF by microinjection of lidocaine (2%, 1-2 microliters) produced strong depression or complete cessation of inspiration. In conclusion, the results of the present study show that the dmNF may play an important role in the neurogenesis of respiratory rhythm.

Animals↗
PubMed1989

[A preliminary study on immune complexes in myasthenia gravis].

The levels of circulating immune complex from 43 patients with myasthenia gravis (MG) and 50 normal controls were detected by using ELISA based on bovine conglutinin. The levels of circulating immune complex in MG patients were higher than those in normal controls (P less than 0.01). Although the levels of circulating immune complex in generalized type MG were higher than those in ocular type MG, the difference showed no statistically significant. It was found that the levels of circulating immune complex, both generalized type MG and ocular type MG, were higher than those in normal controls respectively (P less than 0.01).

Adolescent↗