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Biomedical subjects

X Zhu

Publications and source records attributed to X Zhu.

At least 757 records · Page 42Linked to original sources
PubMed1991

Targeted integration of adeno-associated virus (AAV) into human chromosome 19.

A key feature in adeno-associated virus (AAV) replication is efficient integration of the viral genome into host cell DNA to establish latency when helper virus is absent. The steps involved in this process remain largely uncharacterized, even though AAV integration was first documented 20 years ago. Using a protein--DNA binding method we isolated AAV--cellular junction DNA sequences. The cellular component hybridized to a single restriction fragment in the virus-free parental cell line, and also co-migrated with AAV-specific sequences in numerous latently infected cell lines. Analysis of somatic cell hybrids indicated that this cellular sequence maps to the distal portion of the q arm of human chromosome 19. In situ hybridization of AAV DNA to chromosomes from latently infected cells confirms the physical location of AAV integrations to be q13.4-ter of chromosome 19. Sequence analysis of several independent integration sites shows breakpoints occurring within a 100 bp cellular region. This non-pathogenic parvovirus thus appears to establish viral latency by integrating its DNA specifically into one chromosomal region. Such specific integration is so far unique among the eukaryotic DNA viruses. The incorporation of site-specific integration into AAV vector schemes should make this vector system attractive for human gene therapy approaches.

Base Sequence↗
PubMed1991

Investigation of copper-PTSM as a PET tracer for tumor blood flow.

Copper-PTSM has been shown in previous studies to act as a fluid microsphere and to be useful in quantitating blood flow in brain, myocardium, and kidneys. In this study we have evaluated this agent as a PET tumor blood flow agent. 64Cu- or 67Cu-labeled Cu-PTSM was administered (i.v.) to Golden Syrian hamsters with colorectal carcinoma cell implants (GW39). One minute prior to sacrifice (10-60 min after Cu-PTSM was administered) 125I-iodoantipyrine (125I-IAP), an agent known to measure tumor blood flow, was administered intravenously by a 3-stage, 1 min ramp infusion. Following sacrifice, samples of tumor and brain were removed (within 40s) and the tumor and brain levels of Cu-PTSM and iodoantipyrine determined. Since the brain uptake of both Cu-PTSM and IAP is perfusion rate limited, the brain was used as a reference organ to normalize tumor levels of the two tracers. The plot of Cu-PTSM versus 125I-IAP tumor/brain ratios showed a good linear correlation (r value of 0.97), suggesting that Cu-PTSM could be used to quantify tumor blood flow. Since the mechanism of Cu-PTSM trapping is likely to be due to glutathione levels in the tissue, and because tumor tissue glutathione levels might vary, the temporal uptake of Cu-PTSM was investigated by PET imaging both the tumor-bearing hamsters and approximately 300 g Copenhagen rats bearing R3227 prostate tumors. The tumors were clearly visualized and the retained copper radioactivity in the tumor was constant over the 30 min imaging period.

Animals↗
PubMed1991

Pro-peptide as an intramolecular chaperone: renaturation of denatured subtilisin E with a synthetic pro-peptide [corrected].

The amino-terminal pro-sequence consisting of 77 amino acid residues is required to guide the folding of secreted subtilisin E, a serine protease, into active, mature enzyme (ikemura et al., 1987). Furthermore, denatured subtilisin E can be folded to active enzyme in an intermolecular process with the aid of an exogenously added pro-subtilisin E, the active site of which was mutated (Zhu et al., 1989). In this report, we have synthesized the pro-peptide of 77 residues (corresponding to -1 to -77 in the sequence, where residue +1 is the N-terminal amino acid residue of the mature protein), and have found that it could intermolecularly complement the folding of denatured subtilisin E to active enzyme. Furthermore, we have found that the synthetic pro-peptide exhibits specific strong binding to the active mature enzyme by inhibiting it competitively at its active centre with an upper limit to a Ki of 5.4 x 10(-7). In contrast, synthetic pro-peptides corresponding to -44 to -77, -1 to -64 and -1 to -43 inhibited the enzyme with Ki values weaker by two orders of magnitude. The results indicate that the sequence extending from -1 to -77 is essential for specificity of interaction, perhaps generating a conformation that accounts for both roles found hitherto, i.e. specific binding to the active centre, and guiding of the refolding to active enzyme. Thus these results suggest that the pro-peptide functions as an intramolecular chaperone [corrected].

Chaperonins↗
PubMed1991

The interspersed DNA repeat conserved in water birds' genomes.

A putative old and ubiquitous interspersed DNA repeat family was identified from TaqI restriction, M13 cloning, and sequencing of the genomic DNA of a Mallard (Anas platyrhynchos), a Muscovy Duck (Cairina moschata), a Toulouse Goose (Anser anser), and a Black Swan (Cygnus atratus). A 425-bp consensus core sequence was obtained for the interspersed family. The 425-bp unit was about 2% of the avian genome and was found to be conserved in at least four genera of the order Anseriforme: Anas, Anser, Cairina, and Cygnus.

Animals↗
PubMed1991

[The preparation of highly purified insulin and its clinical use. Insulin Cooperative Study Group].

Antigenicity of insulin preparations is obviously related to their purity. The average contents of proinsulin, glucagon and pancreatic polypeptide in highly purified insulin (HP-I) produced by us are 76.0, 2.11 and 0.11 ppm respectively. These results are superior to those for domestic conventional crystalline insulin and single peak insulin (SP-I). The antibodies to insulin, proinsulin and pancreatic polypeptide in serum were examined in 24 diabetic patients treated with HP-I for more than 6 months. The positive rates for the above three antibodies were 37.5%, 0% and 0% respectively. The results showed that the antigenicity of HP-I was much lower than that of domestic conventional crystalline insulin and almost the same as that of MC-I from Nordisk, Denmark.

Autoantibodies↗
PubMed1991

Subcloning and expression of midecamycin polyketide synthase genes from Streptomyces mycarofaciens 1748.

A 2.4 kb fragment containing the midecamycin polyketide synthase genes (mps) was subcloned from the preliminary clone pCN8B12 out of the genomic library of midecamycin-producing strain S. mycarofaciens 1748, by using the homologous DNA of the actinorhodin polyketide synthase gene (act I) as hybridization probe. This DNA fragment was subcloned onto Streptomyces/E. coli shuttle vector pMHM3. A recombinant plasmid pCG2 was obtained. The transformation of the polyketide synthase deficient mutant of actinorhodin-producing strain, S. colicolor TK17, with pCG2 DNA resulted in the production of an antibacterial compound which was similar neither to actinorhodin nor to midecamycin. The transformation of spiramycin-producing strain S. ambofaciens with pCG2 DNA increased spiramycin production in the fermentation broth. The transformation of the regulatory mutant of daunorubicin-producing strain with pCG2 DNA resulted in the production of epsilon-rhodomycinone verified by TLC and HPLC analyses. The pCG2 DNA also could be functionally expressed in tetracenomycin C-producing strain S. glaucescens. However, it could not be expressed in the blocked mutants of erythromycin-producing strain Saccharopolyspora erythrarea WMH 15,261. These suggest that the pCG2 DNA may complement polyketide synthase gene deficiency or have some regulatory function in certain polyketide antibiotic-producing strains.

Cloning, Molecular↗
PubMed1990

Zhu et al. reply.

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Journal Article↗
PubMed1990

A myo-inositol pool utilized for phosphatidylinositol synthesis is depleted in sciatic nerve from rats with streptozotocin-induced diabetes.

Peripheral nerve from experimentally diabetic rats exhibits lowered levels of myo-inositol (MI) and decreased incorporation of [3H]MI into phosphatidylinositol (PI). There are indications that diminished PI turnover may be causally related to reduced Na+,K(+)-ATPase activity in diabetic nerve. We have investigated whether a metabolic compartment of MI that is essential for PI synthesis is decreased in this tissue. Sciatic nerve segments from streptozotocin-induced diabetic and age-matched normal rats were incubated in vitro with either 32Pi or [3H]cytidine in the presence of propranolol. This cationic amphiphilic agent redirected nerve phospholipid metabolism to produce enhanced 32P incorporation into PI and decreased labeling of phosphatidylcholine and phosphatidyl-ethanolamine. The accumulation of phosphatidyl CMP (CMP-PA) was also demonstrated by chromatographic and enzymatic means. The incorporation of [3H]cytidine into CMP-PA in normal nerve increased up to 15-fold when 0.6 mM propranolol was present. In diabetic nerve, the liponucleotide incorporated 2- to 3-fold more isotope and was more readily labeled at lower drug concentrations as compared to normal nerve. The buildup of [3H]CMP-PA was reduced in a dose-dependent manner in the presence of MI in the incubation medium at concentrations up to 3 mM. However, if MI was added after liponucleotide accumulation, preformed CMP-PA could not be utilized for PI synthesis. The difference in liponucleotide labeling between normal and diabetic nerve was nearly abolished at 0.3 mM medium MI, a concentration much less than the level of cyclitol in the tissue. These results strongly suggest the presence in nerve of a pool of MI that is not in equilibrium with the bulk of nerve MI and that is preferentially used for PI synthesis. This metabolic compartment is depleted in diabetic nerve but can be readily replenished by exogenous MI and may correspond to the MI pool that has been proposed to be required for the turnover of a portion of tissue PI involved in maintenance of normal Na+,K(+)-ATPase activity.

Animals↗
PubMed1990

1,2-diacylglycerol content and its arachidonyl-containing molecular species are reduced in sciatic nerve from streptozotocin-induced diabetic rats.

The content of 1,2-diacylglycerol (DAG) was determined in sciatic nerves from normal and streptozotocin-induced diabetic rats. In nerves frozen in situ, DAG content was reduced 22% in the proximal region and 77% in the distal region of diabetic nerve, principally because of the loss of associated fat. DAG levels in freshly dissected and desheathed diabetic nerve were decreased from 23 to 30% as compared with normal nerve. Determination of DAG molecular species distribution in desheathed normal nerve indicated that 18:0/20:4 accounted for 34%, 16:0/18:1 for 17%, and several other polyunsaturated fatty acid-containing species for 17% of the total. In diabetic nerve, the quantity of the 18:0/20:4 DAG, species was reduced by 37%, and this drop was 62% of the reduction in all molecular species. The content of the minor species, 16:0/20:4 DAG, was decreased by 48%. Our results suggest that nerve DAG arises in large part from phosphoinositide degradation. Moreover, these results provide support for the hypothesis that reduced Na+,K(+)-ATPase activity in diabetic nerve is a consequence of decreased phosphoinositide turnover, which thereby generates insufficient DAG to maintain a protein kinase C-mediated step necessary for activation of Na+,K(+)-ATPase.

Animals↗
PubMed1990

The macrosatellites of the Toulouse goose: the major tandemly repetitive DNA in the toulouse goose genome.

This paper examines the principal classes of repetitive DNA of the Toulouse goose (Anser anser) genome. There are four major classes and they are tandem repeats of less than 200 base pairs (bp). The longest repeat (class A) is 190 bp long and starts with a HinfI site. Class B is 43 bp long, commencing with a FokI site. Classes A and B show no extensive homology to DNA sequences held on a current data base (Genbank) but were confirmed to exist as major repeats in another strain of goose, the Emden goose (Anser anser) genome. Classes C and D are 5-bp repeats of 5' GAGAG 3' and 5' GGGAA 3', respectively. The macrosatellites C and D were compared with a current data base (Genbank) and were found to exist in a variety of other organisms as satellites.

Animals↗
PubMed1990

[Comparative study of serum lipid-bound sialic acid and carcinoembryonic antigen in patients with lung cancer].

Serum LSA and CEA levels were measured in 86 patients with lung cancer, 56 patients with benign pulmonary diseases and 127 normal subjects. The results showed that the diagnostic accuracy rate of LSA for lung cancer (82.4%) was higher than that of CEA (67.6%). LSA was more useful than CEA for diagnosis and differantial diagnosis of lung cancer. CEA was more sensitive to adenocarcinoma of the lung. While LSA was sensitive to small cell lung cancer and squamous cell lung cancer as well. LSA levels and positive rate were related to the stages of lung cancer. LSA was more helpful than CEA for evaluating the status of disease and staging patients. The changes of LSA levels in 33 patients with lung cancer were related to the results of chemotherapy. LSA was superior to CEA for monitoring therapy. Combinative determination of both two markers was better than that of single marker.

Adenocarcinoma↗
PubMed1990

[A comparison of anti-arrhythmic effects of four kinds of rhizoma seu radix Nomopterygii].

Experiments were conducted to compare the anti-arrhythmic effects of the four kinds of Qianghuo(Notopterygium incisum; N. forbesii; Pleurospermum rivulorum; Angelica silvestris). It has been found that all the four kinds of Qianghuo can antagonize arrhythmia induced by aconitine. Notopterygium incisum can prolong the ventricular vibration induced by CaCl2 and Pleurospermum rivulorum can prolong the ventricle stop induced by BaCl2. Thus Qianghuo can be used as a sedative and anti-arrhythmic drug.

Aconitine↗
PubMed1990

Surgical considerations of re-do valve replacement.

Between August 1976 and May 1988, 43 patients had their heart valve prostheses replaced. The total mortality was as high as 25.6%, but the operative mortality was reduced to 6.25% in the last 16 cases. The indications, main risk factors and surgical techniques are discussed.

Adult↗