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Biomedical subjects

Y Yan

Publications and source records attributed to Y Yan.

At least 271 records · Page 15Linked to original sources

The structure of simian virus 40 refined at 3.1 A resolution.

BACKGROUND: The structure of simian virus 40 (SV40), previously determined at 3.8 degree resolution, shows how its pentameric VP1 assembly units are tied together by extended C-terminal arms. In order to define more precisely the possible assembly mechanisms, we have refined the structure at 3.1 degree resolution. RESULTS: New data from a high-intensity synchrotron source have been used for phase extension by electron-density averaging and refinement, exploiting only the strict 5-fold non-crystallographic symmetry for the real-space averaging steps. The accurate model enables us to study important structural features of the virus particle in detail. The remarkably invariant core of the VP1 pentamer bears the docking sites for the C-terminal arms from other pentamers. These contacts are the principal way in which pentameric assembly units are linked together in the capsid. Only at the interface between five-coordinated and six-coordinated pentamers do the pentamer cores appear to interact strongly. There are two cation-binding sites per VP1 monomer, seen in a soaking experiment with gadolinium nitrate. These sites are quite close to each other at the interfaces between pentamers. CONCLUSION: We propose that the contact between five-coordinated and six-coordinated pentamers may help to generate a six-pentamer nucleus, with which further pentamers can assemble to generate the complete particle. Calcium ions probably stabilize the structure of the assembled particle, rather than direct its assembly.

Amino Acid Sequence↗

Effect of domestically-made levonorgestrel-releasing intrauterine device on the endocrine system and menstruation in monkeys.

Effect of domestically-made levonorgestrel-releasing intrauterine device (LNG, release rate, 6 micrograms/day) on the endocrine system and menstruation in monkeys was investigated. The results showed that the Estradiol (E2) and progesterone (P) levels were significantly decreased 2 ovulatory cycles after insertion of the devices as compared with those before insertion in 3 monkeys (P > 0.001), suggesting an evident ovulation-suppressing effect. In 1 monkey, the E2 and P levels were the same before and after insertion, and expulsion of device was found in the monkey later. The plasma LNG concentration in 3 animals was 493.69-454.60 pg/ml and plasma LNG was not detected in 1 monkey. The hormone level returned to normal level after removal of the devices.

Animals↗

Ascaris, people and pigs in a rural community of Jiangxi Province, China.

A longitudinal investigation on natural populations of Ascaris in humans and pigs and an investigation of soil contamination with Ascaris eggs were carried out from June 1993 to June 1994 in 2 villages, Manhu area, Xinjian County, Jiangxi Province, China. Results from these studies indicate that although human ascariasis is endemic there is significant fluctuation in both prevalence and the mean number of eggs/g faeces (epg) of the communities. Fluctuation of age-stratified prevalence and mean epg was detected in children but not in most adult groups. Most cases of human ascariasis were judged to involve low intensities of infection and a typical overdispersion distribution pattern was observed through the year. It was estimated that during the year, nearly half of the eggs discharged in the environment came from infections in children aged between 2 and 15 years which accounted for about 30% of the total population. Soil in and around houses and in vegetable gardens was found to be contaminated by Ascaris eggs and this situation remained relatively stable throughout the year. Monthly developmental rate of Ascaris eggs in soil was detected and the results suggest that the fluctuation in prevalence observed during the year should be directly attributed to the effect of seasonality of egg development. Features of Ascaris infection in pigs were found to be similar to those in humans except for a lower mean intensity of infection. The possibility of cross-infection of Ascaris between human and pig hosts is discussed.

Adolescent↗

In vivo haemoprotective activity of tetrapeptide AcSDKP combined with granulocyte-colony stimulating factor following sublethal irradiation.

We report that acetyl-N-Ser-Asp-Lys-Pro (AcSDKP), which removes progenitor cells from cell cycle, in combination with granulocyte-colony stimulating factor (G-CSF) can significantly improve myelorestoration following irradiation (7 Gy). Peripheral blood, spleen and bone marrow (BM) cell recovery and progenitor cell reconstitution [IL-3-responsive colony-forming cells (CFC) and high proliferative potential colony-forming cells (HPP-CFC)] were studied. Studies on the optimal schedule of AcSDKP administration revealed maximal effects on progenitor cells when AcSDKP was administered as a continuous infusion for 3 d starting 24 h prior to irradiation and used in combination with G-CSF. The numbers of CFC and HPP-CFC in the BM were significantly increased following irradiation in mice receiving AcSDKP and G-CSF as compared to either drug alone. The numbers of CFC in the spleen were significantly increased in mice receiving AcSDKP and G-CSF on days 10 and 14 as compared to AcSDKP alone, but not G-CSF. Similarly, CFC and HPP-CFC in the spleen were significantly increased in mice receiving AcSDKP and G-CSF on day 18 as compared to mice receiving PBS and G-CSF. These studies suggest that AcSDKP in combination with G-CSF may have potential for the protection of progenitor cells in patients undergoing intensive chemo- and/or radiotherapy.

Animals↗

Age-dependent alterations of c-fos and growth regulation in human fibroblasts expressing the HPV16 E6 protein.

Normal human cells in culture become senescent after a limited number of population doublings. Senescent cells display characteristic changes in gene expression, among which is a repression of the ability to induce the c-fos gene. We have proposed a two-stage model for cellular senescence in which the mortality stage 1 (M1) mechanism can be overcome by agents that bind both the product of the retinoblastoma susceptibility gene (pRB)-like pocket proteins and p53. In this study we determined whether the repression of c-fos at M1 was downstream of the p53 or pRB-like "arms" of the M1 mechanism. We examined c-fos expression during the entire lifespan of normal human fibroblasts carrying E6 (which binds p53), E7 (which binds pRB), or both E6 and E7 of human papilloma virus type 16. The results indicate a dramatic change in cellular physiology at M1. Before M1, c-fos inducibility is controlled by an E6-independent mechanism that is blocked by E7. After M1, c-fos inducibility becomes dependent on E6 whereas E7 has no effect. In addition, a novel oscillation of c-fos expression with an approximately 2-h periodicity appears in E6-expressing fibroblasts post-M1. Accompanying this shift at M1 is a dramatic change in the ability to divide in low serum. Before M1, E6-expressing fibroblasts growth arrest in 0.3% serum, although they continue dividing under those conditions post-M1. These results demonstrate the unique physiology of fibroblasts during the extended lifespan between M1 and M2 and suggest that p53 might participate in the process that represses the c-fos gene at the onset of cellular senescence.

Aging↗

Activity of acetyl-n-ser-asp-lys-pro (AcSDKP) on hematopoietic progenitor cells in short-term and long-term murine bone marrow cultures.

The tetrapeptide AcSDKP is a potent inhibitor of hematopoietic stem cell proliferation. Its activity was systematically examined in murine long-term bone marrow cultures (LTBMC) and short-term liquid cultures in the presence or absence of exogenous cytokines. The effects of AcSDKP on the production of granulocyte-macrophage colony-forming cells (CFU-GM) and high proliferative potential colony-forming cells (HPP-CFC) in LTBMCs were examined. AcSDKP was added daily to LTBMCs at various concentrations (10-3--10-16M) for up to 5 weeks. AcSDKP inhibited the entry of progenitor cells into S phase as measured by 3H-thymidine suicide assay and the absolute number of progenitor cells with peak activity at 10-12 M with less activity seen at higher or lower concentrations. The number of nonadherent CFU-GM per LTBMC was unchanged from control values at 1 week of treatment with AcSDKP but was significantly depressed at weeks 3 and 5. In contrast, HPP-CFC progenitor cells were decreased throughout the treatment period, and the numbers of CFU-GM and HPP-CFC in S phase were significantly decreased throughout the treatment period. Maximum S-phase inhibitory activity was observed at 10-12 M AcSDKP. AcSDKP had no effect on the number of adherent CFU-GM or HPP-CFC, cellularity per culture or percent of adherent progenitor cells in S phase. Murine short-term bone marrow cultures were also treated with AcSDKP in the presence or absence of cytokines (interleukin-3 [LI-3], stem cell factor [SCF], or granulocyte colony-stimulating factor [G-CSF]) for various time periods. Dose-response studies showed maximum effects at 10-12 M AcSDKP when no cytokines were added and 10-14 M AcSDKP when exogenous cytokines were added. These studies indicate that the concentration of the tetrapeptide critical in obtaining an effect on hematopoietic progenitor cells, and furthermore, we report that the presence of cytokines or stromal cells also affects the response of progenitor cells to AcSDKP.

Amino Acid Sequence↗

In vivo protective effects of tetrapeptide AcSDKP, with or without granulocyte colony-stimulation factor, on murine progenitor cells after sublethal irradiation.

Acetyl-N-Ser-Asp-Lys-Pro (AcSDKP) demonstrated hemato-protective activity in mice after sublethal irradiation (7 GY). Bone marrow interleukin-3 (IL-3)-responsive colony-forming cells (CFC and high proliferative potential colony-forming cells (HPP-CFC) were significantly (p < 0.05) increased by day 10 after irradiation in mice receiving a continuous infusion of 1000 ng/day of AcSDKP compared to irradiated control mice. The maximum protective effect for bone marrow progenitors was achieved when AcSDKP was administered for 3 days beginning 24 hours before irradiation. Other dosages and schedules in relationship to irradiation were less active. Further, when granulocyte colony-stimulating factor (G-CSF) was administered for 10 days beginning 24 hours before irradiation. Other dosages and schedules in relationship to irradiation were less active. Further, when granulocyte colony-stimulating factor (G-CSF) was administered for 10 days after AcSDKP infusion in irradiated mice, significantly increased numbers of IL-3 responsive CSF-only control mice. In addition, platelets were significantly (p < 0.05) increased in mice receiving AcSDKP and G-CSF on days 18 and 21 after irradiation compared with mice receiving G-CSF alone. We conclude that ACSDKP has a radioprotective effect in vivo for progenitor cells, and that time of initiation and duration of AcSDKP administration relative to irradiation are crucial for these effects. Further, AcSDKP has a significant additive protective effect not only for progenitor cells but also for platelets when given in combination with G-CSF. We suggest that these in vivo observations provide a basis on which to design optimal clinical hypothesis and protocols.

Amino Acid Sequence↗

[Transplantation of pedicled pisiform bone to replace lunate bone with aseptic necrosis].

OBJECTIVE: To find out a new and effective method for the treatment of aseptic necrosis of lunate bone. METHODS: Blood supply and morphology of pisiform bone were investigated in 25 upper limbs and 57 sets of carpal bone from adult cadavers on the basis of anatomical study. The lunate bone was replaced with pisiform bone of pedicled blood vessel and tendon of musculus flexor earpiulnaris in 17 patients with aseptic necrosis of lunate bone (stage III). RESULTS: The patients were followed up for 18-46 months (average of 28 months). Complete relief of pain was obtained in all of the patients, and the range of motion of their wrists was improved. Grip strength was increased by 48.2%. Radiograph showed normal location of transferred pisiform bone without osteosclerosis and atrophy in 16 patients. Atrophy of pisiform bone was found 2 years after operation in one patient. In the 17 patients, 15 resumed their original jobs and 2 changed their jobs for other reasons. CONCLUSION: We consider that the carpal bone chain can be completely preserved by transplantation of pedicled pisiform bone, which it is an effective method to treat aseptic necrosis stage III of lunate bone.

Adult↗

Study on the production of human interferon alpha-2b expressed in Escherichia coli.

The production process of human interferon alpha-2b was established in our institute. The human interferon alpha-2b was expressed in E. coli by using PL promotor. The production process consists of high cell density fermentation, refolding of the inclusion bodies, chromatography with Sephadex G-50 and DEAE, without using monocloning antibody affinity chromatography. After purification, about 500 mg of the human interferon alpha-2b was obtained from 1 kg wet cell harvested from 10 L fermentation broth. The biological activity shows 1-2 x 10(8) IU/mg protein. This production process is very simple and easy to scale-up. If this process adapted, it will save a lot of facility investment, space, and labor. Therefore, the cost will be reduced.

Chromatography, High Pressure Liquid↗

[Study on mechanism of eye-signs in blood stasis syndrome].

Through a study of 504 cases of observation group with eye-signs in blood stasis syndrome (BSS) and 112 cases of control group without eye-signs in BSS, it has been found that in the observation group, the scores of the blood concentration, viscosity, aggregability and coagulability, level of plasma thromboxane B2 (TXB2), and the ratio of TXB2/6-keto-PGF1 alpha were obviously higher than those in the control group, but level of 6-keto-PGF1 alpha was obviously lower than that in the control group; the above-mentioned parameters of blood hyperviscosity syndrome, was obviously higher than that in the control group (90.08%:2.68%); comparisons between the two groups were significantly different (P < 0.001). Certain findings of the pathological base of eye-signs in BSS were found in the investigations.

6-Ketoprostaglandin F1 alpha↗

[Purification and characterization of S-layer protein from Aeromonas hydrophila].

The regular surface protein array (S-layer) present on Aeromonas hydrophila J-1 was composed of a single species of protein of apparent molecular weight 51500. This protein was extracted from whole cells by treatment with 0.2 mol/L glycine hydrocholoide (pH4.0). The protein was purified by Sephadex G-200 gel filtration chromatography and an ion exchange chromatography on DEAE-cellulose. Amino acid composition analysis showed that the protein contained 36.8% hydrophobic amino acids. But the protein did not confer hydrophobicity to the cell surface when present as an intact S-layer by salt aggregation test. ELISA and immunoblotting with two different polyclonal antisera against surface exposed-(PM) and non-surface-exposed epitopes (PR) of the protein revealed that the sensitivity of PM was higher than that of PR. Antigenic diversity of the S-layer proteins from 20 bacterial samples was analysed by ELISA with PM and PF1 (polyclonal antiserum against Aeromonas hydrophila TF7 S-layer protein). The S-layer proteins were distinguishable from the extracellular toxin of the homogeneous strains in antigenic and biochemical characterization and the S-layer proteins were one of the main protective antigens.

Aeromonas hydrophila↗

[Alkaloids in the flowers of Sophora viciifolia Hance].

Six alkaloids have been isolated from the flowers of Sophora viciifolia for the first time. Based on of physico-chemical methods and spectroscopic analysis, their structures have been identified as oxymatrine, oxysophocarpine, sophocarpine, matrine, sophoramine and sophoridine.

Alkaloids↗

[The effect of ligustrazine and 764-3 on type I and type III collagen mRNA expression in fibroblasts].

The effect of ligustrazine and 764-3 on type I and type II collagen mRNA expression in cultured fibroblasts was studied. The results showed that ligustrazine at a final concentration of 30 micrograms/ml for 24 hours could inhibit type I and type II collagen mRNA expression, 764-3 at a final concentration of 15 micrograms/ml for 24 hours could stimulate type I collagen mRNA expression, but exerted no effect on type II collagen expression. The possible mechanism of 764-3 action was discussed.

Cells, Cultured↗

Measurements of membrane diffusing capacity and pulmonary capillary blood volume in normal subjects and patients with mild emphysema.

OBJECTIVE: To establish predicted values of membrane diffusing capacity (Dm) and pulmonary capacity blood volume (Vc), to compare the predicted values from our equations with those for Caucasians, to determine whether there are changes initially in Dm or Vc in patients with mild emphysema. PATIENTS AND METHODS: Diffusing capacity for carbon monoxide (DLco), Dm and Vc were determined in 86 normal subjects and 16 patients using the single-breath diffusing capacity for carbon monoxide (DLcosB) with two different alveolar concentrations of oxygen. RESULTS: The predicted equations are as follows. For males, DLco (ml/min/mm Hg) = 0.37H-0.19A-27.8; Dm (ml/min/mm Hg) = 0.65H-0.24A-53.7; Vc(ml) = 0.88H-78.9. For females, DLco = 0.28H-22.7; Dm = 0.59H-53.6; Vc = 66.6-0.36A. DLco and Vc are lower in Chinese than Caucasians while Dm is similar in Chinese and Caucasians. Eleven of 16 patients had a low DLco (< 80% predicted value), 12 had a low Dm and 5 had a low Vc. Eight of 12 patients with a low Dm also had a low DLco, but in 4 the DLco was normal. Nine of 12 with low Dm had a normal Vc. CONCLUSIONS: This study provides prediction equations of Dm and Vc. Chinese have a low DLco because their Vc is lower than Caucasians. The DLco and Dm are abnormal in a comparable percentage of patients. In patients with mild emphysema, the Dm becomes abnormal before the Vc.

Adolescent↗

[The preliminary study on the hepatitis B virus infection rate of peripheral blood mononuclear cell in both HBsAg and HBeAg-positive pregnant women and its role in intrauterine transmission].

OBJECTIVE: To study the hepatitis B virus (HBV) infection rate of peripheral blood mononuclear cells (PBMC) and the role of infected PBMC in the intrauterine transmission. METHODS: Polymerase chain reaction (PCR) was using for detection of HBV-DNA in PBMC of 52 both HBsAg and HBeAg positive pregnant women just before onset of labour, and HBsAg were detected in sera of their neonates by enzyme linked immunoabsorbent assay (ELISA) within 24 hours after birth. RESULTS: HBV infection rate of PBMC in these women was 46.2% (24/52). There was positive correlation between infection rate of PBMC and HBsAg titre of pregnant women (chi 2 = 4.59, P < 0.05), but no relationship between PBMC infection rate and neonatal HBV infection. CONCLUSION: The possibility of intrauterine transmission of HBV by infected PBMC through transplacental passage was small.

DNA, Viral↗

[Effect of 764-3 and ligustrazine on collagen content of extrapulmonary arteries during chronic hypoxia].

OBJECTIVE: Effect of two antifibrotic Chinese drugs, 764-3 and ligustrazine, on collagen content in chronic hypoxic pulmonary hypertensive extrapulmonary arterial wall were examined. METHODS: Since collagen contains more than 10% hydroxyproline by weight and in other proteins there are almost no hydroxyproline, collagen content was expressed as micrograms of hydroxyproline. Hydroxyproline was determined by calorimetric method after oxidized by chloramine T. RESULTS: Both 764-3 and ligustrazine significantly inhibited the increase of pulmonary arterial pressure and elevation of hydroxyproline content in extrapulmonary arterial wall during chronic hypoxia. CONCLUSIONS: 764-3 and ligustrazine may be two hopeful therapeutic drugs for chronic hypoxic pulmonary hypertension.

Animals↗

Interleukin-12 enhances peripheral hematopoiesis in vivo.

Interleukin 12(IL-12) is a cytokine that supports the proliferation and activation of cytotoxic T lymphocytes and natural killer (NK) cells. Recent evidence has suggested that IL-12 also has hematopoietic activities in vitro. We report studies that show that IL-12 has significant in vivo hematopoietic stimulating activity that includes enhancement of peripheral (splenic) hematopoiesis and mobilization of hematopoietic progenitor cells to the peripheral circulation. A single injection of recombinant murine IL-12 significantly reduced the number of bone marrow (BM) colony-forming unit granulocyte-macrophage (CFU-GM) in a time-dependent manner, while concomitantly stimulating high proliferative potential. In contrast, splenic CFU-GM and HPP were increased in a time- and dose-dependent manner. Chronic administration of IL-12 resulted in significant splenic hyperplasia with increased progenitor cells, increased circulating progenitor cells, and BM hypoplasia with decreased progenitor cells. These data show that IL-12 has significant in vivo hematopoietic effects that include the ability to mobilize progenitor cells to the peripheral circulation, which may prove to be of significant benefit for peripheral blood stem cell transplantation. Thus, IL-12 has potential to be an important agent for clinical transplantation because of its hematopoietic mobilization and its previously shown immune augmenting and therapeutic activities. This combination of hematopoietic and immune functions is unique and not achievable with currently used hematopoietic growth factors.

Animals↗