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Biomedical subjects

F Peng

Publications and source records attributed to F Peng.

At least 19 recordsLinked to original sources

The abnormality of glucose transporter in the erythrocyte membrane of Chinese type 2 diabetic patients.

Type 2 diabetes mellitus is characterized by impaired glucose uptake. With a photometric method of recording the erythrocyte suspension absorption during the course of glucose transport across the membranes, we observed that the initial rate of glucose zero-trans entry was decreased significantly in 30 Chinese type 2 diabetic patients as compared to 25 healthy controls. The rate of glucose infinite-cis efflux exhibited no difference between the patients and controls. The measurement of temperature dependence of glucose transport showed that the activation energy for glucose entry was increased in diabetic patients. The inhibitory constant of glucose entry by cytochalasin B (CB) in patients was similar to that of the controls. However, we found that the inhibitory constant was increased significantly in the patient erythrocytes after phloretin treatment. After the erythrocytes were made into stripped white ghosts, the fluorescence quenching experiment was performed. Glucose, CB and phloretin can quench the fluorescence of tryptophan residues in the glucose transporter 1, GLUT1. The abnormality of fluorescence quenching in the erythrocyte membranes of patients was observed. The transfer tendency of tryptophan residues from the hydrophilic environment to the hydrophobic environment was decreased in patient ghosts as binding with glucose, and the opposite tendency appeared as CB and phloretin instead of glucose. We conclude that the decreased in glucose entry in the erythrocyte membranes of diabetic patients was due to the GLUT1 change in structure - mostly the outer domain of the glucose transporter.

Asian People↗

Cloning and characterization of the cDNA sequences of two venom peptides from Chinese scorpion Buthus martensii Karsch (BmK).

From a cDNA library made from venom glands of Chinese scorpions of Buthus martensii Karsch, full-length cDNAs encoding precursors of two venom peptides have been isolated using a cDNA probe synthesized by polymerase chain reaction. Sequence analysis of the cDNAs revealed that one encoded precursor was 85 amino acid residues long including a signal peptide of 19 residues and a mature peptide (named BmK T) of 66 residues, and another encoded precursor was 84 residues long containing the same length signal peptide and a mature peptide (BmK M4 isoform, named BmK M4') of 64 residues. The analysis of amino acid sequence similarity indicated that the BmK T was homologous with both mammalian and insect toxins from BmK scorpion or other scorpions, and the BmK M4' was highly homologous with the members of the mammalian neurotoxin family of BmK, having two point mutations in amino acid residue sequence compared to BmK M4, a natural toxin from BmK.

Animals↗

Cloning and characterization of a cDNA sequence encoding the precursor of a chlorotoxin-like peptide from the Chinese scorpion Buthus martensii Karsch.

A full-length cDNA sequence encoding the precursor of a venom peptide with homology to chlorotoxin (named BmKCT) was isolated from a cDNA library made from the venom glands of the Chinese Scorpion Buthus martensii Karsch. The encoded precursor of BmKCT was 59 amino acid residues long including a signal peptide of 24 residues and a mature toxin of 35 residues with four disulfide bridges. The sequence of BmKCT is similar (68% identities) to that of chlorotoxin isolated from Leiurus quinguestriatus quinquestriatus. BmKCT is the first report of the cDNA sequences encoding four-disulfide-bridged short-chain toxins from Buthus martensuii Karsch so far.

Amino Acid Sequence↗

Immunotherapy of tumors with xenogeneic endothelial cells as a vaccine.

The breaking of immune tolerance against autologous angiogenic endothelial cells should be a useful approach for cancer therapy. Here we show that immunotherapy of tumors using fixed xenogeneic whole endothelial cells as a vaccine was effective in affording protection from tumor growth, inducing regression of established tumors and prolonging survival of tumor-bearing mice. Furthermore, autoreactive immunity targeting to microvessels in solid tumors was induced and was probably responsible for the anti-tumor activity. These observations may provide a new vaccine strategy for cancer therapy through the induction of an autoimmune response against the tumor endothelium in a cross-reaction.

Amino Acid Sequence↗

Cloning and characterization of a novel cDNA sequence encoding the precursor of a novel venom peptide (BmKbpp) related to a bradykinin-potentiating peptide from Chinese scorpion Buthus martensii Karsch.

Based on the amino acid sequence of a bradykinin-potentiating peptide (Bpp) (peptide K-12) from scorpion Buthus occitanus, a full-length cDNA sequence encoding the precursor of a novel venom peptide (named BmKbpp) related to this Bpp, has been isolated and analyzed. The cDNA encodes a precursor of 72 amino acid residues, including a signal peptide of 22 residues and an extra Arg-Arg-Arg tail at the C-terminal end of the precursor, which have to be removed in the processing step. The C-terminal region (21 residues) of the precursor is homologous (57% identical) with the sequence of peptide K-12. Thus, according to the primary structure of the BmKbpp precursor, there may be a propeptide between the signal peptide and the putative mature BmKbpp at the C-terminal region of the precursor.

Amino Acid Sequence↗

Longitudinal changes in optic disc topography of adult patients after trabeculectomy.

OBJECTIVE: To study longitudinal changes in optic disc topography after trabeculectomy in adult patients. DESIGN: Prospective case series. PARTICIPANTS: Twenty-five eyes of 25 patients undergoing trabeculectomy were enrolled. INTERVENTION: Images of the optic disc were obtained preoperatively and approximately 2 weeks, 4 months, and 8 months after surgery by use of a confocal scanning laser ophthalmoscope (Heidelberg Retina Tomograph). MAIN OUTCOME MEASURES: The topographic optic disc parameters (cup volume, cup area, rim volume, rim area, cup-disc area ratio, mean cup depth, maximum depth, cup shape, and height variation contour) were measured automatically for each image with the Heidelberg Retina Tomograph Software (version 1.11). RESULTS: Approximately 2 weeks after surgery, the mean preoperative intraocular pressure (IOP) of 19.3 mmHg (SD, 6.4 mmHg) decreased to 6.0 mmHg (SD, 3.6 mmHg), cup volume and mean cup depth decreased, height variation contour increased, and the cup shape parameter became more negative. Approximately 4 months after surgery, mean IOP was 9.7 mmHg (SD, 4.2 mmHg), and the only statistically significant change from preoperative values of optic disc parameters was in the cup shape measure. Approximately 8 months after surgery, there was no statistically significant change in any of the optic disc parameters compared with preoperative values, although IOP was 10.4 mmHg (SD, 5.9 mmHg). CONCLUSIONS: Changes in the optic disc that may be present 2 weeks after a trabeculectomy do not appear to persist 4 and 8 months later in eyes with advanced glaucomatous optic nerve damage, except for cup shape, which was different from preoperative values at 4 months but not at 8 months.

Aged↗

Massive and widely distributed splenosis.

A 45-year-old man, seropositive for hepatitis C, was examined because his liver was palpable well below the costal margin. A CT examination revealed multiple nodules within the liver and also several sites of ectopic tissue. The patient had a splenectomy 25 years before. A radiocolloid study showed uptake, consistent with splenosis, in the thorax, abdomen, pelvis, and possibly the left arm. The magnitude of the ectopic tissue, and its multiple locations, indicated the ability of splenic cells to grow in a variety of body sites.

Humans↗

Reciprocal changes in hypothalamic receptor binding and circulating leptin in anorectic tumor-bearing rats.

Although reduced biological activity of the obese gene product, leptin, has been associated with obesity, little information is available concerning leptin alterations during anorexia. Therefore, we measured circulating leptin concentrations and hypothalamic leptin binding in anorectic tumor-bearing and pair-fed control rats. Plasma concentrations of leptin decreased in tumor-bearing rats early in the course of tumor growth, and fell to nearly non-detectable levels during severe anorexia. The pair-fed control rats that ate the same amount of food as did the anorectic tumor-bearing rats exhibited a 50% decrease in plasma leptin concentration. Concentrations of free fatty acids were elevated in both tumor-bearing and pair-fed groups, while circulating levels of triglycerides were increased only in anorectic tumor-bearing rats. Leptin receptor density was doubled in the hypothalamus of tumor bearing rats, while binding affinity was decreased by 50%. These results suggest that peripheral leptin production is down-regulated, perhaps due to increased lipolysis in tumor-bearing rats. It appears that hypothalamic leptin systems up-regulate receptor numbers in response to decreased blood leptin level, however, the decrease in binding affinity may compensate for these alterations. Therefore, the influence of leptin on hypothalamic neuropeptide Y feeding systems may be minimal in anorectic tumor-bearing rats.

Animals↗

Activation of the cyclic AMP pathway by alpha-melanotropin mediates the response of human melanocytes to ultraviolet B radiation.

A hallmark of sun exposure is increased melanin synthesis by cutaneous melanocytes which protects against photodamage and photocarcinogenesis. Irradiation of human keratinocytes or melanocytes with ultraviolet (UV) rays stimulates the synthesis and release of alpha-melanotropin (alpha-MSH) and adrenocorticotropic hormone (ACTH), which induce cyclic AMP (cAMP) formation and increase the proliferation and melanogenesis of human melanocytes. We report that stimulation of cAMP formation is obligatory for the melanogenic response of cultured normal human melanocytes to UVB radiation. In the absence of cAMP inducers, UVB radiation inhibited, rather than stimulated, melanogenesis. UVB radiation (28 mJ/cm2) arrested melanocytes in the G1 phase of the cell cycle, and concomitant treatment with 0.1 microM alpha-MSH enhanced their proliferation but did not increase the surviving fraction. Irradiation with UVB, with or without alpha-MSH, caused prolonged expression of p53 and p21(waf-1, cip-1), maintained pRB in a hypophosphorylated state, and reduced the expression of Bcl2. However, alpha-MSH allowed UVB-irradiated melanocytes to enter S phase, suggesting that alpha-MSH acts as a mitogen rather than a survival factor, and that overexpression of p53 is mainly a signal for cell death. Our results underscore the importance of the cAMP pathway and its physiological inducers in mediating the response of human melanocytes to UV radiation.

Cyclic AMP↗

Identification of functional GRP-preferring bombesin receptors on human melanoma cells.

Bombesin was originally isolated from amphibian skin, whereas its mammalian counterpart, gastrin-releasing peptide (GRP), was first identified in the nervous system of the gastrointestinal tract. Whether GRP is present in the human skin is not known. Bombesin-like peptides are also known to modulate growth. We therefore investigated whether human melanoma cell lines express functional GRP-preferring bombesin receptors and whether they alter growth or other specific cellular functions of these tumour cells. GRP receptor mRNA was found in HBL, D-10, Me-28 and A375-6 cell lines, but only A375-6 cells express a large number of high-affinity binding sites for [125I]-[Tyr4] bombesin (K(d) 0.31 +/- 0.04 nmol L(-1), 3880 +/- 429 binding sites per cell). Bombesin dose-dependently increased cytosolic calcium, but did not alter interleukin (IL) 1beta-induced reduction of cell viability or IL-6 secretion, both A375-6-specific cell functions. Growth of A375-6 cells was not altered by bombesin or the specific GRP receptor antagonist BIM26226 as measured by [3H]-thymidine incorporation or methylene blue assay, whereas insulin alone or in combination with other potential growth factors dose-dependently stimulated growth of these cells. The newly characterized GRP-preferring bombesin receptors on highly malignant human melanoma cells could initiate studies of growth effects on solid tumours or in vivo scanning using radiolabelled tracers.

Bombesin↗

APC-resistance as measured by a Textarin time assay: comparison to the APTT-based method.

Protein C is a major regulatory protein critical to physiologic anticoagulation. When activated, it selectively degrades the activated forms of factors V and VIII, thereby, down-regulating blood coagulation. Using an activated partial thromboplastin time (APTT) assay, Dahlback et al. recently reported that some individuals with thrombophilia show a poor in vitro anticoagulant response to activated protein C (APC-Resistance). Subsequent studies identified a point mutation in the gene for factor V as the underlying cause of APC-Resistance. The incidence of APC-Resistance in patients with recurrent thromboembolic events approaches 50%. The APC-Resistance phenotype is also present in approximately 5% of normal Caucasian subjects. In an attempt to develop a more sensitive and specific test system, we evaluated an assay based on Textarin(Pentapharm, Basel, Switzerland). Textarin, a protein fraction of Pseudonaja textilis venom (Australian Eastern Brown Snake) activates prothrombin in the presence of phospholipid (PL), factor V and calcium ions. Based on Textarin's requirement for factor V, we developed a Textarin time assay to test for APC-Resistance. We evaluated this test system in normal subjects and the following patient populations: stable orally anticoagulated, previously diagnosed factor V Leiden, and therapeutically heparinized samples. We found the Textarin assay to be a sensitive and specific test system to identify APC-Resistance. The phenotypic Textarin APC-Resistance test correlated more closely with the genotypic abnormality of factor VR506Q than the APTT-APC-Resistance test.

Anticoagulants↗

Pulmonary embolism and premature labor in a patient with both factor V Leiden mutation and methylenetetrahydrofolate reductase gene C677T mutation.

Multiple risk factors for thrombosis were found in a 21 year old female who experienced three episodes of premature labor and developed severe pulmonary embolism during her third pregnancy. This patient is heterozygous for factor V Leiden mutation and homozygous for methylenetetrahydrofolate reductase (MTHFR) gene nucleotide 677 C to T (C677T) point mutation. This is a first report of the concordance of homozygous MTHFR C677T mutation in an individual with factor V Leiden mutation. This new case provides further evidence that synergism of multiple genetic and acquired risk factors is often encountered in young patients with symptomatic venous thrombosis.

Adult↗

Bayesian inference for hierarchical mixtures-of-experts with applications to regression and classification.

This paper studies the problems of inference and prediction in a class of models known as hierarchical mixtures-of-experts (HME). The statistical model underlying an HME is a mixture model in which both the mixture coefficients and the mixture components are generalized linear models. Bayesian inference regarding an HME's parameters is presented in the contexts of regression and classification using Markov chain Monte Carlo methods. A benefit of this Bayesian approach is the ability to obtain a sample from the posterior distribution of any functional of the parameters of the given model. In this way, more information is obtained than provided by a point estimate. The methods are illustrated on a nonlinear regression problem and on a breast cancer classification problem. The results indicate that the HME showed good prediction performance, and also gave the additional benefit of providing for the opportunity to assess the degree of certainty of the model in its predictions.

Algorithms↗

Isolation and characterization of cDNAs from BamHI-H gene family RNAs associated with the tumorigenicity of Marek's disease virus.

It has been reported that loss of the tumorigenic potential of attenuated Marek's disease virus (MDV) is strongly associated with amplification of the 132-bp repeat sequences found within the BamHI-D and BamHI-H fragments contained within the long terminal repeat and the long internal repeat, respectively. The expansion of this region results in loss of transcripts that are 3.8, 3.0, and 1.8 kbp long that are produced by tumorigenic strains of MDV. This evidence suggests that production of one or more of these three RNAs is strongly associated with the tumorigenic potential of the virus. In this study, we have cloned and sequenced 1.69-, 1.5-, 1.9-, and 2.2-kbp cDNAs from the BamHI-H gene family RNAs associated with tumorigenicity. The 1.69- and 2.2-kbp cDNAs are derived from nonspliced transcripts, whereas the 1.5- and 1.9-kbp cDNAs are from single spliced mRNAs spanning the BamHI-H and BamHI-I2 fragments of MDV DNA. Sequence analysis has shown two potential open reading frames in each of the cDNAs. The putative 63-amino-acid protein encoded by the first open reading frame in the 1.69-kbp cDNA and a putative 75-amino-acid protein encoded by the first open reading frame in the 1.5-kbp cDNA showed limited homology with the mouse T-cell lymphoma oncogene and the fes/fps family of kinase-related transforming proteins.

Amino Acid Sequence↗