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Biomedical subjects

J Lin

Publications and source records attributed to J Lin.

At least 649 records · Page 36Linked to original sources

Percutaneous transcystic cholangioscopy for combined treatment of gallbladder and bile duct stones.

A procedure for percutaneous transcystic cholangioscopy requiring only one percutaneous transhepatic fistulous tract to remove stones located in both the gallbladder and bile ducts is described. The procedure begins with percutaneous transhepatic drainage of the gallbladder or bile duct. Stones in the gallbladder and bile duct can be removed under direct vision on transhepatic cholangioscopy. Larger stones can be fragmented by electrohydraulic lithotripsy before removal. In a preliminary trial the procedure proved to be a feasible method for treatment of 13 patients with both gallbladder and bile duct stones as well as septic cholangitis who either refused operation or were considered poor candidates for surgery. On long-term follow-up (mean period 28 months) stone recurrence was observed in three patients.

Aged↗

Mitochondrial COII sequences and modern human origins.

The aim of this study is to measure human mitochondrial sequence variability in the relatively slowly evolving mitochondrial gene cytochrome oxidase subunit II (COII) and to estimate when the human common ancestral mitochondrial type existed. New COII gene sequences were determined for five humans (Homo sapiens), including some of the most mitochondrially divergent humans known; for two pygmy chimpanzees (Pan paniscus); and for a common chimpanzee (P. troglodytes). COII sequences were analyzed with those from another relatively slowly evolving mitochondrial region (ND4-5). From class 1 (third codon position) sequence data, a relative divergence date for the human mitochondrial ancestor is estimated as 1/27 th of the human-chimpanzee divergence time. If it is assumed that humans and chimpanzees diverged 6 Mya, this places a human mitochondrial ancestor at 222,000 years, significantly different from 1 Myr (the presumed time of an H. erectus emergence from Africa). The mean coalescent time estimated from all 1,580 sites of combined mitochondrial data, when a 6-Mya human-chimpanzee divergence is assumed, is 298,000 years, with 95% confidence interval of 129,000-536,000 years. Neither estimate is compatible with a 1-Myr-old human mitochondrial ancestor. The mitochondrial DNA sequence data from COII and ND4-5 regions therefore do not support this multiregional hypothesis for the emergence of modern humans.

Animals↗

Combination anti-CD2 and anti-CD3 monoclonal antibodies induce tolerance while altering interleukin-2, interleukin-4, tumor necrosis factor, and transforming growth factor-beta production.

OBJECTIVE: These studies were designed to elucidate the mechanism by which signals delivered by anti-CD2 monoclonal antibody (MoAb) interfere with activational signals delivered by anti-CD3 MoAb and induce long-term graft survival and tolerance. SUMMARY BACKGROUND DATA: Anti-CD2 or anti-CD3 MoAb can prolong allograft survival when administered alone. In combination, they synergistically prolong survival while reducing anti-CD3-associated cytokine toxicity. It was postulated that the mechanism of synergism and reduced cytokine toxicity was related to anti-CD2-induced alterations in anti-CD3-induced T-cell activation. METHODS: C57BL/6 (H-2b) mouse hearts were transplanted to CBA (H-2k) mice. The recipients received anti-CD2 and/or anti-CD3 MoAb intravenously only at the time of initial allografting. Serum from treated animals and culture supernatants from lymphocytes stimulated in vitro with anti-CD3 were examined for interleukin (IL)-2, -4, -6, and -10, tumor necrosis factor (TNF), and transforming growth factor-beta (TGF beta). RNA was isolated from lymphocytes from treated animals and examined for receptor and cytokine gene expression by northern hybridization or reverse transcribed and amplified by the polymerase chain reaction (PCR). RESULTS: Anti-CD2 and anti-CD3 MoAbs alone prolonged graft survival (22.0 +/- 0.5 days and 28.0 +/- 0.5 days, respectively; p < 0.02 and p < 0.01 vs. control, by Wilcoxon signed-rank test). Combined anti-CD2/anti-CD3 MoAbs synergistically prolonged survival indefinitely (> 150 days, p < 0.01) while decreasing cytokine toxicity. Second donor-specific allografts also showed long-term survival. The peak serum TNF concentration (2100 units/mL) was reduced 78% by anti-CD2 treatment (455 units/mL). Anti-CD2 inhibited anti-CD3-stimulated proliferation and in vitro production of IL-2 and IL-4, with no alteration of IL-6, IL-10, or TNF. Conversely, there was an increase in the immunosuppressive cytokine TGF beta. PCR analysis showed that anti-CD2 reduced anti-CD3-stimulated IL-2 messenger RNA expression, and by northern analysis, anti-CD2 inhibited anti-CD3-stimulated increases in messenger RNA for the CD2 and CD3 receptors themselves. CONCLUSIONS: The combination of anti-CD2 and anti-CD3 MoAbs induced a state of tolerance while decreasing anti-CD3-associated cytokine toxicity. The mechanism was related to anti-CD2-generated alterations in T-cell activation and gene expression.

Animals↗

Anti-CD2 and anti-CD3 monoclonal antibodies synergize to prolong allograft survival with decreased side effects.

Anti-CD3 monoclonal antibody suppresses immunity and prolongs allograft survival; however, it induces T cell activation and overproduction of soluble factors that result in a deleterious cytokine syndrome. Anti-CD2 mAb also prolongs allograft survival, by suppression of mature and precursor CD4 and CD8 T cells and NK cells, without an associated cytokine release. Because of the close physical and functional association of CD2 and CD3 on the T cell surface, we tested whether alpha CD2 mAb in combination with alpha CD3 mAb could act synergistically to prolong allograft survival, and whether the combination would affect the alpha CD3-associated cytokine syndrome. C57BL/6 (H-2b) hearts were transplanted to CBA (H-2k) recipients in a heterotopic nonvascularized model. Recipients received alpha CD2 (12-15) or alpha CD3 (145-2C11) mAb i.v. alone or in combination. Lymphocytes from treated animals were also analyzed by fluorescent flow cytometry and stimulated in vitro and assessed for proliferation and lymphokine production. Anti-CD2 and alpha CD3 each prolong allograft survival (mean survival time 22.4 +/- 1.0 and 27.4 +/- 3.3 days, respectively vs. 14.0 +/- 0.6 for control mAb, P < 0.001 for both vs. control). Combinations of mAbs show a more complicated interaction. Very low doses (1 microgram) of alpha CD2 and alpha CD3, which have no effect when given alone, are synergistic (16.5 +/- 1.3 days, P < 0.02). A high dose of alpha CD2 (100 micrograms), which is immunosuppressive, is additive with a moderate dose of alpha CD3 (10 micrograms), which is immunostimulatory. The two mAbs are again synergistic when a high dose of alpha CD2 (100 micrograms) is combined with a high dose of alpha CD3 (1 mg) (> 51.5 +/- 23.0 days, P < 0.001). Furthermore, high-dose alpha CD2 administered 48 h prior to high-dose alpha CD3 was a more effective combination for prolonging allograft survival than both antibodies administered simultaneously (67.1 +/- 10 vs. 35.8 +/- 0.7 days, P < 0.05). Anti-CD2 also diminishes the alpha CD3-associated cytokine syndrome, and prior in vivo treatment with alpha CD2 decreases the subsequent in vitro proliferative response to alpha CD3 and the alpha CD3-stimulated production of IL-2 and IL-4. Flow cytometry demonstrates that in general these mAbs do not deplete but leave T cell populations intact with altered receptor expression. These results show that the combination of alpha CD2 and alpha CD3 mAbs prolongs cardiac allograft survival in a synergistic fashion while decreasing the side effects of alpha CD3 mAb alone.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

The promoter of the gene encoding 3',5'-cyclic adenosine monophosphate (cAMP) response element binding protein contains cAMP response elements: evidence for positive autoregulation of gene transcription.

The transcriptional transactivational activities of the phosphoprotein cAMP-response element-binding protein (CREB) are activated by the cAMP-dependent protein kinase A signaling pathway. Dimers of CREB bind to the palindromic DNA element 5'-TGACGTCA-3' (or similar motifs) called cAMP-responsive enhancers (CREs) found in the control regions of many genes, and activate transcription in response to phosphorylation of CREB by protein kinase A. Earlier we reported on the cyclical expression of the CREB gene in the Sertoli cells of the rat testis that occurred concomitant with the FSH-induced rise in cellular cAMP levels and suggested that transcription of the CREB gene may be autoregulated by cAMP-dependent transcriptional proteins. We now report the structure of the 5'-flanking sequence of the human CREB gene containing promoter activity. The promoter has a high content of guanosines and cytosines and lacks canonical TATA and CCAAT boxes typically found in the promoters of genes in eukaryotes. Notably, the promoter contains three CREs and transcriptional activities of a promoter-luciferase reporter plasmid transfected to placental JEG-3 cells are increased 3- to 5-fold over basal activities in response to either cAMP or 12-O-tetradecanoyl phorbol-14-acetate, and give 6- to 7-fold responses when both agents are added. The CREs bind recombinant CREB and endogenous CREB or CREB-like proteins contained in placental JEG-3 cells and also confer cAMP-inducible transcriptional activation to a heterologous minimal promoter. Our studies suggest that the expression of the CREB gene is positively autoregulated in trans.

Amino Acid Sequence↗

Novel role of human chorionic gonadotropin in differentiation of human cytotrophoblasts.

Our laboratory previously demonstrated that cytotrophoblasts and syncytiotrophoblasts in human placental tissue contain hCG/LH receptors. From this finding, we postulated that one role of hCG might be to promote the differentiation of cytotrophoblasts into syncytiotrophoblasts. To test this postulate, cytotrophoblasts were isolated from human term pregnancy placentas and cultured with and without increasing concentrations of highly purified hCG. The results showed that hCG had a biphasic effect on 1) the aggregation of cells without intervening plasma membranes; 2) the expression of cadherin, a cell adhesion receptor that facilitates cellular aggregation; 3) the expression of hCG/LH receptor gene; and 4) the expression of three different hormonal markers of differentiation. The hCG effects were time and dose dependent and hormone specific. The addition of excess polyclonal hCG antibody, but not normal rabbit serum or nonspecific antirabbit immunoglobulin G, decreased basal responses as well as those to exogenous hCG. The polyclonal hCG/LH receptor antibody increased differentiation and dramatically stimulated hCG secretion in the presence or absence of exogenous hCG. (Bu)2cAMP mimicked the actions of hCG. H-89, a protein kinase-A inhibitor, decreased basal as well as exogenous hCG responses. Calphostin, a protein kinase-C inhibitor and lavendustin, a tyrosine kinase inhibitor, on the other hand, had no effect. In summary, it is novel that hCG made in human placenta can regulate the differentiation of cytotrophoblasts, which make little hCG, into syncytiotrophoblasts, which make considerable amounts of hCG.

Blotting, Northern↗

[Experimental research of acupuncture manipulation of reinforcing and reducing by lifting and thrusting needle on the animal].

The experiment were performed on model rabbits injected with large dosage of Dexamethasone (DXM) for 5 days. Reinforcing manipulation (RIM), reducing manipulation (RDM), and electric stimulation (ES) were respectively used to puncture Zusanli (ST 36) points for 5 days to observe the change on temperature, body weight, corticosterone assay, testosterone assay, and the amplitude of the plethysmogram. The result showed that there was a similar syndrome of the kidney deficiency after injecting DXM. The body weight was increased in the DXM control group, decreased in the RDM group and had no significant influence in the other groups. The body weights between the reinforcing manipulation and the reducing manipulation groups had obvious difference. But the other indices of observation had no significant influence among the different groups. So there wasn't significant difference on most of observed signs among the RIM group, the RDM group and ES group. The study of acupuncture manipulation will have yet to be further done.

Acupuncture Therapy↗

[PCR amplification of nerve growth factor (beta-NGF) gene in human brain].

Nerve growth factor, an important nutrition factor for neuronal survival, growth, development and maintenance of neuronal functions, consists of three kinds of subunit (alpha 2, beta and gamma 2), but only the subunit beta-NGF has the biological activity. beta-NGF coding sequence is located in a single exon of NGF gene. In our study, a pair of specific primers (29 mers) has been designed and synthesized with ABI 318 A DNA synthesizer. The upstream primer includes an initiation codon and the 1st to 20th base of the exon. The downstream primer includes the complementary sequence of 334 to 354 base of the exon and a stop codon. The full-length DNA fragment of beta-NGF gene has been successfully obtained from human brain cDNA library in lambda ZAPII/EcoRI and human brain genomic DNA respectively by using polymerase chain reaction. The reaction program consists of denaturing at 93 degrees C for 1 min, annealing at 55 degrees C for 1 min, and extending at 72 degrees C for 2 min. Both amplified products of 350 bp in length coincide with the exon coding sequence and are enough for the analysis of restriction mapping, DNA sequencing and construction of expression vector.

Brain↗

[Pathologic classification of 435 primary orbital tumors].

This paper analysed the pathologic classification of 435 primary orbital tumors, which were mainly divided into eight types, including 83 cases (19.1%) of cystic lesions, 64 cases (14.7%) of vasculogenic lesions, 50 cases (11.5%) of mesenchymal tumors, 73 cases (16.8%) of lacrimal gland epithelial lesions, 54 cases (12.4%) of neural tissue tumors, 55 cases (12.6%) of lymphocytic lesions, 16 cases (3.7%) of histiocytic lesions and 40 cases (9.2%) of idiopathic orbital pseudotumor. The clinicopathologic characteristics of the common orbital tumors were also discussed.

Adolescent↗

[Pathologic, electron microscopic and experimental examination of band keratopathy].

One hundred and thirteen cases previously diagnosed as band keratopathy were reexamined by light microscopy and histochemistry, 10 cases of which were studied by TEM and 2 cases were studied by SEM. We find that the calcium deposition initially occur as fine calcific particles within the cytoplasm of epithelic cells and in the basal membrane and bowman's layer, which aggregated to form calcific spherules and large calcific masses extracellularly. When 3 normal corneal tissues were frozen and cultured, the calcium deposition occur in the superficial layer of bowman's membrane and in the stromal lamellae, Authors suggest that the degeneration and calcific abnormal metabolism of the cell caused by various factors is the main pathogenesis that leads to the calcific deposit. The evaporation and constructive destruction of the corneal surface in the interpiperbral area inhibits the formation of the lacrimal membrane and results in deposition of calcium salts in the superficial tissue of exposed cornea in a band configuration. The combination of glycosaminoglycan with calcium salts is the dynamics of aggregation of the fine calcific particles to form the calcific spherules and calcific masses.

Calcium↗

[Reversal of adriamycin resistance by verapamil and ligustrazini in mouse Ehrlich ascites cancer].

The effectiveness of adriamycin (ADR) in the treatment of cancer has been limited by the development of drug resistance. Verapamil and ligustrazini were found to show significant potentiating effect on the cytotoxicity of ADR in vitro and decreased the IC50 of ADR by 84.85% and 30.82% of the resistant line, respectively, and no effect was found on the IC50 in the sensitive line. The Glutathione-S-transferase activity of ADR-resistant and sensitive mouse EAC was determined in vivo. The activity in resistant cancer was 1.72-fold higher than that in sensitive cancer. Administration of verapamil or ligustrazini decreased the GST activity of resistant EAC by 35.50% or 26.05%, respectively and no effect was observed on sensitive cancer. The results show that verapamil and ligustrazini can reverse partly the ADR-resistance in resistant mouse EAC.

Animals↗

[The type of leptospirosis epidemic and serogroup transformation in Fujian province in recent years].

By analysis of investigations in recent years in Fujian province, it was found that the main type of leptospirosis epidemic was rice-field type, the other was flood type which had the tendency to shift from coastal plain area to northwest area. In the main epidemic area, Wupin county, the detection rate of Hebdomadis serogroup rate sharply declined (P < 0.01), however, that of Batavia serogroup markedly increased (P < 0.01).

Animals↗

Regulation of basal tyrosine phosphorylation of the B cell antigen receptor complex by the protein tyrosine phosphatase, CD45.

Signal transduction via the B cell AgR complex has recently been shown to be dependent on the activation of one or more protein tyrosine kinases. Similarly, it has been found that signal transduction requires the expression of the protein tyrosine phosphatase CD45. Thus, transduction of a signal after AgR cross-linking must involve the coordinate interaction of these two enzymatic activities. It is therefore logical to hypothesize that the competence of the B cell to respond to ligands that bind the AgR may be dependent on the maintenance of an equilibrium between the tyrosine phosphorylation and dephosphorylation of specific signal transduction components. We have demonstrated in the present study that in resting B cells, the basal level of AgR complex tyrosine phosphorylation is regulated by cellular protein tyrosine phosphatases. Treatment of cells with the protein tyrosine phosphatase inhibitor, Na3VO4, resulted in rapid hyperphosphorylation of the receptor complex. Based on this observation, experiments were designed to examine the role of CD45 in regulation of AgR complex phosphorylation. Treatment of B cells with anti-CD45 mAb alone was found to have no effect on cytoskeletal association of CD45 or on its distribution within the membrane. Addition of a secondary cross-linking reagent, however, induced the association of CD45 with the cytoskeleton and caused capping. Subsequent studies demonstrated that increased tyrosine phosphorylation of the mIg-associated proteins MB-1 and B29 could be induced after incubating cells with anti-CD45 mAb and a secondary cross-linker, but not after the addition of anti-CD45 mAb alone. Changes in tyrosine phosphorylation of MB-1 and B29 were found to correlate with the cytoskeletal association of CD45. Interestingly, although cross-linking CD45 induced alterations in its association with the cytoskeleton and in its distribution within the membrane, no significant change in the level of protein tyrosine phosphatase activity could be detected under these conditions. These findings support the possibility that ligand binding to CD45 can induce biochemical and/or physical alterations in the molecule that presumably inhibit its ability to interact with specific substrates in the cell, thereby shifting the established equilibrium between tyrosine-specific phosphorylation and dephosphorylation.

Animals↗

Crystal structure of TFIID TATA-box binding protein.

The structure of a central component of the eukaryotic transcriptional apparatus, a TATA-box binding protein (TBP or TFIID tau) from Arabidopsis thaliana, has been determined by X-ray crystallography at 2.6 A resolution. This highly symmetric alpha/beta structure contains a new DNA-binding fold, resembling a molecular 'saddle' that sits astride the DNA. The DNA-binding surface is a curved, antiparallel beta-sheet. When bound to DNA, the convex surface of the saddle would be presented for interaction with other transcription initiation factors and regulatory proteins.

Amino Acid Sequence↗

The MB-1/B29 heterodimer couples the B cell antigen receptor to multiple src family protein tyrosine kinases.

The B cell Ag receptor complex is comprised of membrane (m)IgM or mIgD noncovalently associated with one or more heterodimers, each containing one subunit of MB-1 (IgM alpha or IgD alpha) and one of B29 (Ig beta or Ig gamma). It is known that cross-linking of the B cell Ag receptor results in protein tyrosine kinase activation. Recent reports from other laboratories have demonstrated that mIg coprecipitates with multiple src family protein tyrosine kinases, including blk, lyn, and fyn. However, the mechanism by which these kinases are physically coupled to the Ag receptor has not been confirmed. It has been hypothesized that the mIg-associated proteins MB-1 and B29 provide a physical link between the Ag receptor (mIg) and one or more protein tyrosine kinases. In this study, we confirm previous findings demonstrating that the B cell Ag receptor coprecipitates with the MB-1/B29 heterodimer as well as the protein tyrosine kinases blk, lyn, and fyn under mild detergent conditions (1% digitonin). Additionally, we demonstrate that in detergent conditions (1% Nonidet P-40 (NP-40)) which disrupt the association between mIg and the MB-1/B29 heterodimer, no protein tyrosine kinase activity can be detected in association with mIg. These findings indicated that NP-40 effectively dissociates the B cell Ag receptor from ancillary signal transducing proteins. MB-1 and B29 were however, found to coprecipitate with blk, lyn, and fyn isolated from B cell lysates containing 1% NP-40. No significant difference was observed in the stoichiometry of association between the kinases and the MB-1/B29 heterodimer in the presence of 1% NP-40 when compared to 1% digitonin. It was further determined that in resting B cells, only a small fraction (approximately 1-3%) of the MB-1/B29 heterodimers appear to be complexed with protein tyrosine kinases. Finally, based on preclearing experiments, it appears that individual heterodimers may associate with a single species of protein tyrosine kinase. These data support the hypothesis that the MB-1/B29 heterodimer couples the antigen receptor to protein tyrosine kinases, thereby providing a physical link that facilitates Ag receptor-mediated regulation of kinase activity.

Animals↗