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Biomedical subjects

J Pan

Publications and source records attributed to J Pan.

At least 181 records · Page 10Linked to original sources

Preclinical studies of glimepiride.

The treatment of NIDDM is advancing on a number of fronts, ranging from the understanding of the mechanisms of action of existing agents to the development of new drugs. Glimepiride, the most recently U.S. approved sulfonylurea, is evaluated for its pancreatic and extrapancreatic activities in addition to safety, when compared with glibenclamide in preclinical studies. Glimepiride uniquely binds to the 65 kDa protein K(ATP) channel in pancreatic islet beta-cell membranes and directly stimulates insulin secretion. Glimepiride has a lower binding affinity and causes less insulin release than glibenclamide in normal dogs and humans. However, in various animal models, glimepiride produces a more rapid and pronounced blood glucose-decreasing activity than glibenclamide. In vivo studies indicate that glimepiride also significantly reduces HbA1c, blood glucose and fasting insulin levels via extrapancreatic activities. These insulin mimetic effects are supported by demonstration of stimulated lipogenesis in 3T3 adipocytes and glycogenesis in rat diaphragm, by more efficient translocation of GLTU4 in fat and skeletal muscle tissues, and by activation of key metabolic enzymes. The insulin sensitivity effects of glimepiride have been demonstrated in vivo by increased glucose disposal rates in euglycemic clamp studies and in vitro by increased sensitivity and responsiveness of insulin-induced glucose uptake. Moreover, glimepiride might stimulate insulin-mediated glucose utilization in hepatocytes. With exercise-induced hypoglycemia, a suppression of endogenous insulin secretion was observed for glimepiride only. Data accumulated from in vitro and animal studies suggest that glimepiride has the least cardiotoxic potential. Its relative activities in multiple cardiovascular studies do not correlate with its potency to lower blood glucose levels. Similar cardiovascular effects have been seen in human studies. In contrast to the lack of an acute action, chronic application of glimepiride to cultured cardiomyocytes was found to produce an approximate doubling of the basal glucose uptake rates by an insulin-independent pathway most probably involving increased protein expression of both GLUT1 and GLUT4. Like glibenclamide, glimepiride possibly has antiatherogenic activity by inhibiting platelet aggregation via suppression of arachidonic acid metabolism. Our recent studies on rats and humans indicated that glimepiride has immunomodulatory activity and this action appears to be related to lowering autoimmune responses rather than metabolic action. These studies have been extended to include glimepiride involvement with prevention of diabetes in BB rats using an islet transplantation model. Finally, sulfonylureas, including glimepiride, may be useful for treating and preventing NIDDM.

Journal Article↗

Expression profile of senescence-associated beta-galactosidase and activation of telomerase in human ovarian surface epithelial cells undergoing immortalization.

Senescence is a specific physiological stage of cells characterized by long population doubling time. It accounts for the inability of normal somatic cells to undergo indefinite cell division. As the number of population doublings increase, cell cycle regulatory mechanisms come into play and signal cells to exit the cell cycle and become senescent. Senescence has been implicated in the aging process and may function as a tumor suppressor mechanism in human cells. The ability to measure the degree of cellular senescence is important in understanding the biological processes regulating cell aging and immortalization. Senescent cells exhibit an enzyme termed senescence-associated histochemical staining. Cells immortalized by viral oncogenes often enter a stage of crisis at the early phase of immortalization. The cells at crisis have a long population doubling time. Cells at the crisis stage resemble senescent cells and the expression of SA- beta-Gal may be used to monitor the process of immortalization. In this study the expression profile of SA-beta-Gal was examined in human ovarian surface epithelial cells (HOSE 6-3) undergoing immortalization by the human papilloma viral oncogene E6 and E7 (HPV E6 and E7). Our results showed a low percentage (12.0%) of HOSE 6-3 cells expressing SA-beta-Gal activity at the pre-crisis stage. The percentage of HOSE 6-3 cells expressing SA-beta-Gal activity was highest (39.2%) at the crisis stage. When HOSE 6-3 cells achieved immortalized status there was a sharp decrease in cells (1. 3%) expressing SA-beta-Gal activity. In addition, an inverse relationship between the expression of SA-beta-Gal activity and telomerase activity was noted in cells undergoing immortalization. The results confirm that the SA-beta-Gal enzyme is a good marker for monitoring the population of cells undergoing senescence at different stages of immortalization and that telomerase activation is a characteristic feature of post-crisis cells.

Biomarkers↗

[The influence of immediate postpartum insertion of GyneFix PP-intrauterine devices on puerperal period].

OBJECTIVE: To investigate the effects of immediate postpartum insertion of GyneFix PP-intrauterine devices (IUD) on postpartum hemorrhage, bloody lochia and postpartum endometritis. METHODS: 126 women had GyneFix PP-IUD inserted immediately postpartum (IUD group) and another 118 cases with no IUD insertion were served as control. Blood loss during delivery, 2 and 24 hours after delivery were determined, the time of bloody lochial lasted and the incidence of postpartum endomeritis were recorded. RESULTS: There were no significant differences in the blood loss during and after delivery, and the incidence of endometritis between the 2 groups, but the bloody lochia was lasted significantly longer in the IUD group (P < 0.05). CONCLUSION: This results suggested that the immediate postpartum insertion of the GyneFix PP-IUD is a safe and good postpartum contraceptive method, and the cause of prolonging bloody lochia awaits for further study.

Adult↗

[Induction of hematopoietic cell apoptosis by the serum from immune-mediated aplastic anemia mice].

OBJECTIVE: To explore the mechanism of the impairment of hematopoietic stem/progenitor cells in aplastic anemia(AA) mice. METHODS: The hematopoietic cells from normal mice bone marrow were incubated with serum from AA mice in the presence of recombinant GM-CSF and IL-3. Parallel controls, i.e. hematopoietic cells from normal mice with or without serum of normal mice, were conducted. At different time, samples were collected and detected by flow cytometry (FACS), transmission electron microscopy (TEM) and gel electrophoresis. RESULTS: In the 16 post hour-culture of the experimental group mice: (i) The percentages of apoptotic cells were increased. (ii) Hematopoietic cells showed nuclear condensation, margination and blebbing under TEM. (iii) Agarose gel electrophoresis of DNA from the 13,000x g supernatant showed a ladder pattern. The percentage of DNA fragmentation measured by diphenylamine reaction was also increased and (iv) ZnSO4, cycloheximide and actinomycin D could partially suppress the induction of DNA fragmentation and delay the ocurrence of apoptosis. CONCLUSION: Apoptosis occurs in hematopoietic cells when incubated with serum from immune-mediated AA mice.

Anemia, Aplastic↗

[Incidence, risk and prognostic factors of pneumonia acquired at intensive care units].

OBJECTIVE: To estimate the incidence of pneumonia acquired in the intensive care unit, and to define risk factors for developing such an event. METHOD: A total of 158 patients were retrospectively analyzed and 108 of them acquied pneumonia at ICU of Zhongshan Hospital (surgical ICU and respiratory ICU) and Huashan Hospital (general ICU) from January 1996 to November 1997. Statistical analysis was made using SPSS, odds ratios and stepwise logistic regression analysis were used to determine the interrelationships between multiple variables. Statistical significance was predetermined to include p values of < 0.05. RESULT: The following five factors were significantly (P < 0.05) associated with HAP: cancer [OR = 6.73, 95% CI = 1.58 to 28.59], treatment with H2-blockers (OR = 5.5742, CI = 1.94 to 15.99), decreased consciousness (OR = 3.30, CI = 1.52 to 7.18), use of urethral catheters (OR = 1.07, CI = 1.01 to 1.13), and mechanical ventilation (OR = 1.05, CI = 1.00 to 1.01). The risk facors for HAP were different among different ICU. The risk of developing pneumonia increased when depressed level of consciousness and mechanical ventilation were present at general ICU. Factors significantly predisposing to HAP were underlying COPD, using H2-blockers and mechanical ventilation at respiratory ICU, and previously lower respiratory tract infection was the risk factor for HAP in surgical ICU. The following factors were associated with a significantly higher fatality rate in HAP patients: depressed level of consciousness (P = 0.02), previously lower respiratory tract infection (P = 0.001), and long-time mechanical ventilation (P = 0.03). CONCLUSION: The risk factors for HAP were different among different ICU, which may be related to the difference of patients with an ultimately or a rapidly fatal underlying illness admitted to these units.

Cross Infection↗

[Effect of qingjieling induced endogenous granulocyte-colony stimulating factor in strengthening host defence against bacteria].

OBJECTIVE: To explore the effect of Qingjieling (QJL) induced endogenous granulocyte-colony stimulating factor (G-CSF) in strengthening host defence against bacteria in mice. METHODS: Serum containing G-CSF was obtained by injecting 5 mg/g of QJL to mice. The CSF activity was identified by ELISA, bone marrow cell proliferation and colony-forming assays. Forty-eight hours after the serum was infused to 8 normal BALB/C mice, the mice was sacrificed and the number of E. coli in spleen suspension was measured. Eight mice of the control group were treated in the same way but with normal serum of mice instead of the QJL treated serum. RESULTS: The QJL treated serum showed a positive reaction with anti-G-CSF McAb, it promoted the proliferation of bone marrow cells and formation of cell colony of neutrophilic granulocyte type in the culture medium, these results indicated that the serum contained G-CSF undoubtedly. The number of E. coli in spleen suspension of test group was significantly lower than that of the control group P < 0.01). CONCLUSIONS: QJL does enhance the defense capability of the host, the mechanism of which partly might be due to the induction of endogenous G-CSF in the host.

Animals↗

[Studies on the solvent structure in protein crystals grown in microgravity].

Structures of Space- and ground-grown protein crystals were determined and compared for hen egg-white lysozyme and acidic phospholipase A2 from snake venom. The results show that microgravity might improve the structure of weakly bound ordered water molecules, though it could not change the protein conformation and the structure of solvent molecules bound stronger to protein molecules. The results also imply that the degree of quality improvement of microgravity-grown protein crystals might be related to the solvent content in protein crystals. These findings might, in a respect, reveal the mechanism of quality improvement of protein crystals grown in microgravity. In addition, due to the importance of water molecules in life activities, the confirmation of this preliminary conclusion might enlighten guidance in further studies of life science in microgravity.

Crystallization↗

[Analysis of constituents of essential oils from flos Magnoliae].

The constituents of essential oils from Magnolia biondii, M. denudata and M. sprengeri were analysed by GC-MS qualitatively and GC quantitatively. Ninety-one compounds of M. biondii, seventy-one compounds of M. denudata and eighty-eight compounds of M. sprengeri were identified at rates of 97.37%, 97.66% and 95.68% respectively.

Acyclic Monoterpenes↗

[A methodological study of frequency domain analysis on heart rate variability and RT interval variability].

Recently, heart rate variability (HRV) as a non-invasive measure for assessing the balance of autonomic nervous system has drawn more attentions and HRV analysis has become a focus of the ECG signal processing. QT interval represents the ventricular repolarization duration. QTV might reflect the balance of autonomic nervous system in other way. QTV analysis might complement HRV analysis. Because of the difficulty in detecting QT interval, RT interval is often used instead of QT interval. HRV and QTV detecting methods have been presented in this paper. After recording 24 h ECG signals, R fiducial marks are detected correctly and ectopic beats are removed. T peaks are detected on the basis of templet matching and correlation. The analysis in frequency domain consists of 24 h 3-dimensional frequency chart, as well as trends of HF/LF and HF, with fast Fourier transform and autoregressive techniques. We acquired ECG signals from subjects under controlled respiration in different frequencies. The results of HRV and RTV spectral analysis have shown that HF peak is modulated at the frequency of controlled respiration, which proves that HF peak is dependent on the vagal activity and our method is correct. The establishment of these methods has provided a basis for further research, and the development of HRV and QTV analysis techniques will be more helpful for early diagnosis, monitoring and prognostic assessment of some diseases.

Algorithms↗

[Effects of artemisia capillaris on blood glucose and lipid in mice].

The effects of Artemisia capillaris Thunb (AC) on blood glucose and lipid in mice were studied and its effective mechanism was explained. The results showed that hyperglycemic effect in aloxan-induced mice was inhibited (P < 0.01); that hyperglycemica in DM mice was decreased (P < 0.05); but the change of fasting blood glucose (FBG) in normal and hyperlipidemia mice was not significant (P < 0.05); that the level of total cholesterol (TC) and/or atherosclerotic index (AI) was decreased (P < 0.01-0.05) and the content of high density lipoprotein cholesterol (HDL-C) was increased in the above different model mice (P < 0.01-0.05). These results indicated that the AC would have the similar hypoglycemic effect as biguanide-drugs, improve endogenous and exogenous metabolic derangement in blood lipid. These suggest that AC could be used to protect and treat DM and its chronic complication.

Alloxan↗

Spatiotemporal changes in cytokeratin expression in the neonatal rat ovary.

Ovarian granulosa cells are derived embryologically from two keratin-positive epithelia of mesodermal origin, the ovarian rete and the ovarian surface epithelium. In the rat, presumptive granulosa cells still express keratin at birth but as they acquire functions related to oocyte support and steroidogenesis in the maturing ovary they lose this epithelial differentiation marker. Using double-label immunofluorescence microscopy, we examined the distribution of keratin-expressing granulosa cells in rat ovaries on days 1-10 postpartum in relation to (i) laminin and collagen type IV in follicular basement membranes, (ii) the zona pellucida, and (iii) 3 beta-hydroxysteroid dehydrogenase activity. Keratin was present in most (pre)granulosa cells on days 1-3. As the cells became multilayered in growing follicles, keratin was retained by granulosa cells adjacent to follicular basement membranes but disappeared from cells that were displaced towards follicular centers. From day 7 on, large follicles lacked keratin altogether. Laminin was a consistent component of follicular basement membranes at all ages, while collagen IV varied and diminished in parallel with keratin. 3 beta-Hydroxysteroid dehydrogenase was demonstrable in stromal interstitial cells from day 7 on. Zona pellucida first appeared in primary follicles adjacent to keratin-positive cells and subsequently became surrounded with keratin-negative granulosa cells in growing follicles. The results suggest different roles for laminin and collagen IV in follicular basement membranes and support the hypothesis that keratin expression by granulosa cells depends on paracrine interactions with the ovarian stroma. In early growing follicles, these interactions may be interrupted by physical removal from the vicinity of the basement membranes as the granulosa cells become multilayered. In the more mature follicles, the loss of keratin from all granulosa cells suggests that the required stromal signals cease, perhaps as the perifollicular stroma differentiates into the theca.

Animals↗

Frequent abnormalities of TSG101 transcripts in human prostate cancer.

TSG101 has been identified as a candidate tumor suppressor gene and abnormal transcripts have been identified in a substantial fraction of breast cancers. To determine whether TSG101 expression is commonly altered in other tumors, a series of 15 primary and metastatic prostate cancers were analysed by reverse transcriptase-PCR amplification. Abnormal transcripts with extensive deletions in the coding region were found in nine of these tumors, while only the normal transcript was found in control and benign prostatic hypertrophy tissues. More than one abnormal transcript was found in four of these nine cases and distinct abnormal TSG101 transcripts were found in separate biopsies taken from one tumor. Importantly, the normal TSG101 transcript was undetectable in two metastatic prostate cancers, indicating the absence of TSG101 protein. Sequence analysis demonstrated that there were at least six distinct deletions, with four of these deletions found in more than one tumor sample. The most commonly identified deletion, from bp 153 to 1055, was identical to a deletion reported previously in breast cancer. These results demonstrate that TSG101 transcripts are frequently abnormal in prostate cancer and suggest that loss of TSG101 protein contributes to disease development or progression.

Base Sequence↗

Folding of RNA involves parallel pathways.

Folding kinetics of large RNAs are just beginning to be investigated. We show that the Tetrahymena self-splicing RNA partitions into a population that rapidly reaches the native state, and a slowly folding population that is trapped in metastable misfolded structures. Transitions from the misfolded structures to the native state involve partial unfolding. The total yield of native RNA is increased by iterative annealing of the inactive population, and mildly denaturing conditions increase the rate of folding at physiological temperatures. These results provide the first evidence that an RNA can fold by multiple parallel paths.

Animals↗

Studies on Interaction of Dodecyltrimethylammonium Bromide with Na- and Al-Montmorillonite

The adsorption isotherms and adsorption enthalpies of dodecyltrimethylammonium bromide (DDTMAB) on Na- and Al-montmorillonite were determined in the pH range 2-12. The basal spacings of the clays were also studied by X-ray diffraction. Interactions of DDTMAB with the two montmorillonites predominate mostly through cation exchange in the pH range studied. In the case of Na-montmorillonite, the amount of adsorption increases with pH, but adsorption enthalpy decreases with pH. For Al-montmorillonite, adsorption enthalpy exhibits nonmonotonic variation with pH, although the amount of adsorption increases with pH monotonously. The adsorption enthalpies of DDTMAB on the clays are negative. The adsorbed DDTMAB molecules in clay interlayers present a bilayer arrangement at saturation. Copyright 1997 Academic Press. Copyright 1997Academic Press

Journal Article↗

Androgen receptor-associated protein complex binds upstream of the androgen-responsive elements in the promoters of human prostate-specific antigen and kallikrein 2 genes.

An increasing number of proteins which bind to hormone-dependent nuclear receptors and mediate their effects on gene expression are being identified. The human prostate-specific antigen (PSA) and kallikrein 2 (KLK2) genes are regulated by the androgen receptor (AR). Using electrophoresis mobility shift assays (EMSA), a common nuclear protein(s) which binds upstream of the androgen-responsive elements (AREs) in the PSA and KLK2 promoters was identified. Binding occurred between bp -539 and -399 and bp -349 and -224 in the PSA and KLK2 promoters respectively, which were shown previously to be necessary for AR-mediated transactivation. Glutathione S-transferase (GST)-AR fusion proteins were constructed to determine whether the AR interacted directly with this protein or protein complex. Specific interactions were observed with AR fusion proteins containing the DNA binding domain. EMSA supershift experiments and GST-AR pull-down experiments followed by Western blotting identified a Fos-related protein(s) of approximately 40 kDa as part of this complex. Competition experiments with a double-stranded oligonucleotide containing an AP-1 binding site demonstrated that DNA binding was not mediated by AP-1. These results indicate that a Fos-containing protein complex distinct from AP-1 binds upstream of the AREs in the PSA and KLK2 promoters, interacts with the AR and may participate in regulation of these two androgen-responsive genes.

Amino Acid Sequence↗

Corrosion resistance for biomaterial applications of TiO2 films deposited on titanium and stainless steel by ion-beam-assisted sputtering.

The high corrosion resistance and good biocompatibility of titanium and its alloys are due to a thin passive film that consists essentially of titanium dioxide. There is increasing evidence, however, that under certain conditions extensive titanium release may occur in vivo. An ion-beam-assisted sputtering deposition technique has been used to deposit thick and dense TiO2 films on titanium and stainless steel surfaces. In this study, using the following measurements these TiO2 films have been investigated in a phosphate-buffered saline solution: (1) open-circuit potential versus time of exposure, (2) electrochemical impedance spectroscopy, (3) potentiodynamic polarization, and (4) Mott-Schottky plot. A higher electrical film resistance, lower passive current density, and lower donor density (in the order of 10(15) cm-3) have been measured for the sputter-deposited oxide film on titanium in contrast to the naturally formed passive oxide film on titanium (donor density in the order of 10(20) cm-3). The improved corrosion protection of the sputter-deposited oxide film can be explained by a low defect concentration and, consequently, by a slow mass transport process across the film. As opposed to TiO2 on titanium, a deviation from normal n-type semiconducting Mott-Schottky behavior was observed for TiO2 on stainless steel.

Biocompatible Materials↗

New spin labeled analogues of podophyllotoxin as potential antitumor agents.

Four new nitroxyl labeled derivatives of podophyllotoxin, 4-(2, 2, 6, 6-tetramethyl-1-oxyl-4-piperidyl)oxy-epipodophyllotoxin (4), 4-(2, 2, 6, 6-tetramethyl-1-oxyl-4-piperidyl)oxy-4'-demethylepipodophyllotoxin (5), 4-(2, 2, 5, 5-tetramethyl-1-oxyl-3-pyrrolinyl)formyloxy-epipodophyllotox in (6) and 4-(2, 2, 5, 5-tetramethyl-1-oxyl-3-pyrrolinyl)formyloxy-4'-demethylep ipodophyllotoxin (7), have been synthesized and evaluated for their antitumor activity in vitro. Compounds 5 and 7 showed superior activity to clinically used etoposide (VP-16,2) in their inhibition of leukemia P388, lung cancer A549 and stomach carcinoma SGC-7901 cells. 4'-Demethyl-epipodophyllotoxins 5 and 7 was found to be more active than eipodophyllotoxins 4 and 6 lacking a free phenolic hydroxyl group at C-4'.

Animals↗

Impaired gastric myoelectrical activity in patients with chronic renal failure.

Dysmotility and delayed emptying of the stomach have been reported in patients with chronic renal failure (CRF). The aim of this study was to investigate whether gastric myoelectrical activity was impaired in patients with CRF using electrogastrography. The electrogastrogram (EGG) was recorded in 24 symptomatic patients with CRF (15 with diabetes) and 12 normal subjects. Two 30-min EGG recordings before and after a test meal were analyzed using spectral analysis methods. It was found that patients with CRF showed a significantly lower percentage of normal 2-4 cpm slow waves in both fasting and fed states in comparison with healthy controls (in fasting state: 88.9 +/- 2.5% vs 67.4 +/- 6.6%/63.2 +/- 7.0%, P < 0.01; in fed state: 89.6 +/- 1.8% vs 64.6 +/- 6.2%/62.0 +/- 8.3%, P < 0.01; controls vs diabetic patients/nondiabetic patients). Both patient groups showed a significantly higher prevalence of the abnormal EGG, which was defined as the percentage of 2-4 cpm slow waves lower than 70% (fasting state: 8% vs 60%/56%, P < 0.01/0.05; fed state: 0% vs 53%/56%, P < 0.005/0.002; controls vs diabetic patients/nondiabetic patients). No significant difference was observed in the regularity of the gastric slow waves between the two patient groups. The healthy controls showed a significant increase in the dominant power and frequency of the EGG after the test meal. However, this increase was absent in the two patient groups. It was concluded that patients with chronic renal failure have abnormal gastric myoelectrical activity, including impaired regularity of the gastric slow wave and a failed increase in the power of the EGG at 3 cpm. Electrogastrography is an attractive noninvasive method for the study of gastric motility in patients with severe chronic renal failure.

Adult↗