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Biomedical subjects

S Fu

Publications and source records attributed to S Fu.

At least 91 records · Page 5Linked to original sources
PubMed1997

Biochemistry and pathology of radical-mediated protein oxidation.

Radical-mediated damage to proteins may be initiated by electron leakage, metal-ion-dependent reactions and autoxidation of lipids and sugars. The consequent protein oxidation is O2-dependent, and involves several propagating radicals, notably alkoxyl radicals. Its products include several categories of reactive species, and a range of stable products whose chemistry is currently being elucidated. Among the reactive products, protein hydroperoxides can generate further radical fluxes on reaction with transition-metal ions; protein-bound reductants (notably dopa) can reduce transition-metal ions and thereby facilitate their reaction with hydroperoxides; and aldehydes may participate in Schiff-base formation and other reactions. Cells can detoxify some of the reactive species, e.g. by reducing protein hydroperoxides to unreactive hydroxides. Oxidized proteins are often functionally inactive and their unfolding is associated with enhanced susceptibility to proteinases. Thus cells can generally remove oxidized proteins by proteolysis. However, certain oxidized proteins are poorly handled by cells, and together with possible alterations in the rate of production of oxidized proteins, this may contribute to the observed accumulation and damaging actions of oxidized proteins during aging and in pathologies such as diabetes, atherosclerosis and neurodegenerative diseases. Protein oxidation may also sometimes play controlling roles in cellular remodelling and cell growth. Proteins are also key targets in defensive cytolysis and in inflammatory self-damage. The possibility of selective protection against protein oxidation (antioxidation) is raised.

Animals↗
PubMed1997

Effect of the photoperiod in modulating the androgenic control of 1-alkyl-2,3-diacylglycerol composition in the harderian gland of the golden hamster, Mesocricetus auratus.

The golden hamster Harderian gland produces a lipid secretion consisting mainly of 1-alkyl-2,3-diacylglycerol. We investigated the composition of alkyl and acyl groups in male and female hamster Harderian alkyldiacylglycerol, in animals kept in long and short photoperiods. Female hamsters in long days have alkyl groups with long saturated straight chains (C18:0 and C20:0) and methyl-branched chains (even and odd chain length iso-branched and odd chain length anteiso-branched chains). Acyl groups in females in long days are mostly long straight chains (C16:0) and methyl-branched chains. In females, short photoperiods led to reductions in the proportions of methyl-branched chains and changes in the proportions of straight chain alkyl and acyl groups; these changes were prevented by pinealectomy. Male hamsters with intact gonads, maintained in long days, had no methyl-branched chain alkyl or acyl groups; saturated straight chains were generally shorter than those of females and the odd chain length saturated C15:0 acyl group was common. Short photoperiods did not significantly alter the composition of male alkyldiacylglycerol. Castrated male hamsters in long days showed a distinctively female phenotype, with long straight chains and methyl-branched alkyl and acyl groups. Castrated males in short days showed a mixture of male and female characteristics: shorter straight chain alkyl and acyl groups, a total absence of methyl-branched alkyl groups, and the presence of methyl-branched acyl groups. These results and those of other studies suggest that testosterone controls the enzymes isovaleryl acyl-CoA dehydrogenase and 2-methyl branched-chain acyl-CoA dehydrogenase; in the absence of these enzymes, the primers for the synthesis of methyl-branched chain fatty acids are produced. Our results indicate that this control is modulated by short photoperiods (perhaps due to reduced prolactin levels). It is also suggested that characteristics of male-type alkyldiacylglycerol are better adapted to conditions of autumn and winter than are those of female-type alkyldiacylglycerol.

Animals↗
PubMed1997

[Effect of light colours and illumination intensity on the sexual behaviour of Hepialus gonggaensis Fu et Huang].

The sexual behaviour of Hepialus gonggaensis has close relations with ecological environment and varies with its ecotypes. The more intense the illumination, the faster the sexual drive of Hepialus gonggaensis begins and the longer its sexual intercourse continues, light colours have a bearing on its sexual intercourse time. This study has provided an evidence for the artificial cultivation of Hepialus gonggaensis.

Animals↗
PubMed1997

[The simultaneous analysis of substance P, somatostatin, neurokinin and neurotensin by capillary zone electrophoresis].

Neuropeptides play an important part in several different areas of neurochemistry. Recently, capillary electrophoresis (CE) was developed for analysis of neuropeptides. This paper reports a capillary zone electrophoretic method for the simultaneous separation and quantitative determination of the substance P (SP), somatostatin (SS), neurokinin (NKA) and neurotensin (NT). The separation was performed on a 50microm x 60cm fused-silica capillary using 0.1mol/L at pH 2.7 phosphate as buffer. The eluted fractions were detected at 214nm.

Electrophoresis, Capillary↗
PubMed1997

[Simultaneous analysis of theophylline, phenobarbital, amobarbital and carbamazepine in serum by high performance liquid chromatography].

Theophylline, phenobarbital, amobarbital and carbamazepine are the chief therapeutic drugs in clinical practice. Because of the differences among inter-individuals in the metabolic clearance of these drugs and their toxicity at certain levels of concentration in serum, the dosage should be regulated to maintain a therapeutic blood drugs level. To achieve this a rapid and accurate assay method for drugs in blood is necessary. This paper reports that a reversed phase high performance liquid chromatographic (HPLC) method had been established for the simultaneous separation and quantitative determination of the four drugs in serum. The separation was performed on RP-C18 column using methanol:water (1:1) as mobile phase and 4-aminoantipyrime as internal standard. The eluted substances were detected at 210nm.

Amobarbital↗
PubMed1997

[Histomorphometric study of the effect of nylestriol on bone turnover in ovariectomized rabbits].

OBJECTIVE: To assess the effect of Nylestriol on postmenopausal osteoporosis in an attempt to reveal its mechanism. METHODS: Thirty-seven month-old female New Zealand white rabbits were randomized into 3 groups (10 rabbits per group): treatment group [ovariectomized (OVX) + nylestriol (2 mg, monthly)], OVX control group (OVX + vehicle) and normal control group (sham operation + vehicle). Six months later, all rabbits were subjected to tetracycline labelling and then were killed. Under VIDAS system, bone turnover was assessed by bone histomorphometry. RESULTS: Bone volume trabecular (BV/TV), relative osteoid volume (OV/BV), osteoblastic index (OBI) and bone formation rate at tissue level [BFR(T)] increased in treatment group compared with OVX control group and (or) sham control group. CONCLUSIONS: Nylestriol can increase the number of osteoblast, which resulted in more bone matrix production and consequently converted the bone turnover of OVX rabbits to a positive balance situation. It indicated that Nylestriol was probably a stimulator for osteoblast recruitment and (or) proliferation.

Animals↗
PubMed1997

[Suppression of metastatic phenotype of cloned mouse lung adenocarcinoma cells by transfer of human genomic DNA].

OBJECTIVE: To isolate and identify human sequences with metastatic suppression ability. METHODS: Genomic DNA fragments isolated from normal human lung tissue were transfected into cloned highly metastatic mouse lung adenocarcinoma cells together with PSV2neo as selectable marker. RESULTS: 25 transfectants were cloned in medium containing G418 and Ouabain. Eight morphologically flat revertants exhibited a more normal phenotype, six clones containing human DNA were identified by a sensitive Inter Alu-PCR method. The rate of cell growth and colony formation in agar were detected in vitro. Clone 12, 20 and 32 showed a lower ratio than maternal untransfected cells. In vivo clone 12 showed more significent less spontaneous metastases in nude mice and syngeneic T739 mouse than control group. CONCLUSION: The results indicated that the inserted human DNA may be responsible for suppression of metastatic phenotype of mouse lung adenocarcinoma cells.

Adenocarcinoma↗
PubMed1997

[Relationship between umbilical blood lead level and neonatal neurobehavioral development].

Umbilical blood lead level, as an indicator for intrauterine exposure to lead, and neurobehavioral score, as an effect indicator, were determined in 101 neonates in Beijing area to explore the relationship between intrauterine lead exposure and neonatal neurobehavioral development. Results revealed that there was a negative relationship between neonatal umbilical blood lead level and their neurobehavioral score and behavioral ability. With umbilical blood lead level of 0.48 mumol/L as a cutoff value, there was a significant difference in neonatal behavioral ability score between groups of high and low blood lead levels. There also were significant differences in nonbiologically auditory and biological visual and auditory orientation reaction. It suggests that intrauterine lead exposure can cause adverse effects on neonatal neurobehavioral development, especially on their visual and auditory function.

Auditory Perception↗
PubMed1996

Primary structure of trypsin inhibitors from Sicyos australis.

Three trypsin inhibitors from Sicyos australis, have been isolated, purified and sequenced. Following protein extraction with ammonium sulphate, the mixture of inhibitors was separated from other proteins by trypsin-affinity chromatography. Subsequent purification of the individual inhibitors was accomplished by reversed-phase HPLC. The primary structures of each inhibitor were elucidated by a combination of protein sequencing and electrospray ionization mass spectrometry (ESI-MS) and tandem mass spectrometry (MS-MS) on both the untreated and the reduced and S-carboxymethylated inhibitors. All three inhibitors show extensive sequence similarity with inhibitors from cultivated Cucurbitaceae species, although there are a number of novel residues present. One of the inhibitors has a blocked N-terminus (pyroglutamic acid) and the use of MS-MS was crucial to the elucidation of its primary structure. ESI-MS was further used to characterize the non-covalent complex between one of the inhibitors and trypsin.

Amino Acid Sequence↗
PubMed1996

Lack of X inactivation associated with maternal X isodisomy: evidence for a counting mechanism prior to X inactivation during human embryogenesis.

We have previously reported functional disomy for X-linked genes in females with tiny ring X chromosomes and a phenotype significantly more abnormal than Turner syndrome. In such cases the disomy results from failure of these X chromosomes to inactivate because they lack DNA sequences essential for cis X inactivation. Here we describe a novel molecular mechanism for functional X disomy that is associated with maternal isodisomy. In this case, the severe mental retardation and multiple congenital abnormalities in a female with a mosaic 45,X/ 46,X,del(X)(q21.3-qter)/ 46X,r(X) karyotype are associated with overexpression of the genes within Xpter to Xq21.31 in many of her cells. Her normal X, ring X, and deleted linear X chromosomes originate from the same maternal X chromosome, and all are transcriptionally active. None expresses X inactive specific transcript (XIST), although the locus and region of the putative X inactivation center (XIC) are present on both normal and linear deleted X chromosomes. To our knowledge, this is the first report of a functional maternal X isodisomy, and the largest X chromosome to escape inactivation. In addition, these results (1) show that cis inactivation does not invariably occur in human females with two X chromosomes, even when the XIC region is present on both of them; (2) provide evidence for a critical time prior to the visible onset of X inactivation in the embryo when decisions about X inactivation are made; and (3) support the hypothesis that the X chromosome counting mechanism involves chromosomal imprinting, occurs prior to the onset of random inactivation, and is required for subsequent inactivation of the chromosome.

Cell Division↗
PubMed1996

Approaches and reconstruction in skull base operation.

OBJECTIVE: To design convenient lateronasal and infrafrontal approaches or lateronasal subvolution approach to radically resect skull base tumors involving cranial cavity. METHODS: From 1987 through 1994, 22 patients with malignant tumors, 6 with benign tumors, one with a giant sphenoid sinus cyst and one with intranasal meningoencephalocele underwent the operation. Twenty-three cases had anterocranial fossa involved; 4, midcranial fossa; 2, anteromedial cranial fossa; and 1 case, posteromedial cranial fossa. Among the patients with malignant tumors, 11 underwent expansive maxillectomy and 10 had orbital contents resected. The intracranial approaches through lateronasal and infrafront (21 cases), nasal columella lateral subvolution (3 cases) and other approaches were used. RESULTS: The reconstruction of bony skull base defect in excess of 3.00 cm x 3.00 cm with total front musculocutaneous flap (8 cases), galeal and pericranial flap (5 cases) or other tissues (3 cases) has effectively prevented meningoencephalocele. Twelve cases had the dura resected in a range of 2.00 cm x 2.00 cm to 7.00 cm x 6.00 cm. Reconstruction of the dura defect with autofascia lata in 9 cases and other tissues in 3 cases effectively prevented the cerebrospinal fluid leak. Eight of 22 (36.4%) patients with malignant tumors have been alive and free of disease for 3-7 years after the operation. Six patients with benign tumors, one patient with giant sphenoid sinus cyst and one with meningoencephalocele were cured with this reconstructing method. CONCLUSIONS: Frontal musculocutaneous and pericranial flaps have advantages over free bone because of easy surviving and easy operating without occurrence of osteonecrosis and exclusive reaction.

Adolescent↗
PubMed1996

[Intestinal flora in renal allograft recipients].

OBJECTIVE: To explore the change of 10 kinds of intestinal flora in renal allograft recipients and its significance. METHODS: Ten kinds of intestinal flora in faeces were investigated in 30 renal allograft recipients by Kang Bai's classification of flora, and compared with 100 patients with diarrhea and 30 normal controls. RESULTS: The number of enteric bacilli in renal allograft recipients (8.5 +/- 1.0 CFU/g) was increased more markely than in the diarrhea patients (7.7 +/- 1.1 CFU/g, P < 0.01). The number of bacteroid (7.8 +/- 0.6 CFU/g), bifidobactercium (7.7 +/- 0.3 CFU/g), eubaclerium (7.2 +/- 0.6 CFU/g), and clostridium (7.8 +/- 0.5 CFU/g) in renal allograft recipients were decreased more markedly in than normal control (8.2 +/- 0.7 CFU/g, P < 0.01, 8.3 +/- 0.7 CFU/g, P < 0.01, 8.1 +/- 0.9 CFU/g, P < 0.01, 8.0 +/- 0.8 CFU/g, P < 0.01), but the number of Bifidobactercum was higher than that is the diarrhea patients (7.3 +/- 0.6 CFU/g, P < 0.01). The number of eubacterium was Lower than that in the diarrhea patients (7.7 +/- 0.8 CFU/g, P < 0.01). Among 30 renal allograft recipients 3 had constipation and 20 diarrhea. Two cases died of toxic shock with serious diarrhea because of imbalance of intestinal flora. CONCLUSION: The imbalance of intestinal flora existes in the early stage of renal transplantation. It is characterized by anaerobic bacilli imabalance such as bifidobacteriam and may be a direct cause of intestinal infection as diarrhea.

Adolescent↗
PubMed1995

Biological fate of amino acid, peptide and protein hydroperoxides.

In the course of searching for a suitable marker for studying protein oxidation, we have successfully elucidated the structures of three valine hydroperoxides, i.e. beta-hydroperoxyvaline, (2S,3S)-gamma-hydroperoxyvaline and (2S,3R)-gamma-hydroperoxyvaline, which are novel products of protein oxidation. The corresponding valine hydroxides were obtained by sodium borohydride reduction [Fu, Hick, Sheil and Dean (1995) Free Rad. Biol. Med. 19, 281-292]. We hypothesized that valine hydroxides might be the major biological degradation products of valine hydroperoxides and, as such, could be useful markers for the study of protein oxidation in vivo. The aim of this study was to investigate the fate of valine hydroperoxide in selected biological systems by the use of chemiluminescence detection of hydroperoxides and HPLC analysis of O-phthaldialdehyde derivatives of amino acid residues. The degradation of hydroperoxides present on gamma-radiolysed solutions of valine, Pro-Val-Gly, or BSA occurred in the presence of: (1) transition metals (Fe2+, Fe3+, or Cu2+), (2) the detoxifying enzyme GSH peroxidase, (3) human plasma, and (4) J774 mouse monocyte macrophage cells. The major degradation product of valine hydroperoxide recovered in each case was found to be a valine hydroxide. These results suggest that valine hydroxide (derived from the hydroperoxide) may well be a useful in vivo marker for studying protein damage under oxidative stress.

Amino Acid Sequence↗
PubMed1995

Protein hydroperoxides can give rise to reactive free radicals.

Proteins damaged by free-radical-generating systems in the presence of oxygen yield relatively long-lived protein hydroperoxides. These hydroperoxides have been shown by e.p.r. spectroscopy to be readily degraded to reactive free radicals on reaction with iron(II) complexes. Comparison of the observed spectra with those obtained with free amino acid hydroperoxides had allowed identification of some of the protein-derived radical species (including a number of carbon-centred radicals, alkoxyl radicals and a species believed to be the CO2 radical anion) and the elucidation of novel fragmentation and rearrangement processes involving amino acid side chains. In particular, degradation of hydroperoxide functions on the side chain of glutamic acid is shown to result in decarboxylation at the side-chain carboxy group via the formation of the CO2 radical anion; the generation of an identical radical from hydroperoxide groups on proteins suggests that a similar process occurs with these molecules. In a number of cases these fragmentation and rearrangement reactions give rise to further reactive free radicals (R., O2-./HO2., CO2-.) which may act as chain-carrying species in protein oxidations. These studies suggest that protein hydroperoxides are capable of initiating further radical chain reactions both intra- and inter-molecularly, and provide information on some of the fundamental mechanisms of protein alteration and side-chain fragmentation.

Amino Acids↗
PubMed1995

Structural identification of valine hydroperoxides and hydroxides on radical-damaged amino acid, peptide, and protein molecules.

We have previously demonstrated the formation of two reactive moieties on proteins during free radical attack: hydroperoxides, and 3,4-dihydroxyphenylalanine (DOPA). Here we have undertaken the structural elucidation of the hydroperoxides of valine, the amino acid which is most susceptible to peroxidation. Exposure of L-valine to free radicals generated by radiolysis in an oxygen-saturated system produced three valine hydroperoxides. Upon treatment with sodium borohydride these were reduced to their corresponding hydroxides, which can be separated and purified by high performance liquid chromatography (HPLC). Based on spectroscopic data from high resolution chemical ionization (CI) mass spectrometry (MS), electrospray (ES) MS, electron impact (EI) MS, proton (1H) nuclear magnetic resonance (NMR) and carbon-13 (13C) NMR studies, the three valine hydroxides have been identified as beta-hydroxyvaline [(2S)-2-amino-3-hydroxy-3-methyl-butanoic acid], (2S,3S)-gamma-hydroxyvaline [(2S,3S)-2-amino-3-hydroxymethyl-butanoic acid], and (2S,3R)-gamma-hydroxyvaline [(2S,3R)-2-amino-3-hydroxymethyl-butanoic acid]. HPLC analysis of O-phthaldialdehyde (OPA) derivatives of the hydroxyvalines provides a sensitive and accurate method for quantitative measurement. This method enabled hydroxyvalines to be detected in the hydrolysates of a tripeptide (glutamyl-valinyl-phenylalanine) and a protein (bovine serum albumin) that had been gamma-radiolysed and treated with sodium borohydride. Hydroxyvaline may be useful as a marker in studying protein oxidation in some biological systems under oxidative stress.

Amino Acids↗
PubMed1995

Transduction of MDR1 into human and mouse haemopoietic progenitor cells: use of rhodamine (Rh123) to determine transduction frequency and in vivo selection.

The MDR1 gene product P-glycoprotein (P-gp) extrudes several anticancer drugs including taxol and fluorescent dyes such as rhodamine (Rh123). Modulation of the level of P-gp expression has the potential of overcoming multidrug resistance. One possible approach is the retroviral transfer of the human MDR1 gene into murine and human bone marrow (BM) progenitor cells. The rationale for this approach is increased chemoprotection, which allows chemotherapy of a greater level of intensity to be delivered. In this study, flow cytometric measurement of Rh123 extrusion was used to test P-gp function in human and mouse haemopoietic progenitor cells, which had been transduced with a virus containing the human MDR1 transcription unit. Human CD34+ selected cells were analysed immediately following transduction. In two successive experiments MDR1 cDNA transduction resulted in a 7% and 11% increase of P-gp expressing Rh123 dull cells. To monitor transduction efficiency over time as well as the possibility of in vivo selection of drug-resistant BM cells in mice treated with increasing numbers of taxol cycles, the assay was also successfully applied to peripheral blood lymphocytes of mice transplanted with MDR1 transduced BM cells, demonstrating increased Rh123 efflux in transduced cells. Analysis of another fluorescence assay using fluorescein di-beta galactopyranoside as a substrate for beta-galactosidase in cells transduced with a MDR1: beta-gal activity. We conclude that the Rh123 efflux assay is a sensitive method to monitor P-gp function in MDR1 cDNA transduced cells, and may be used to enrich transduced cells via flow cytometric cell sorting for Rh123 dull cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗