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Biomedical subjects

G Zhu

Publications and source records attributed to G Zhu.

At least 163 records · Page 9Linked to original sources

Coronary angiographic characteristics in unstable angina pectoris.

OBJECTIVE: To investigate the angiographic characteristics of coronary lesions in patients of different subgroups of unstable angina pectoris. METHODS: Coronary angiograms and clinical manifestations were analysed on 388 patients. RESULTS: Single-vessel disease was more common in new onset effort angina (69.64%) than in other subgroups (P < 0.05); triple-vessel disease and left main coronary artery disease appeared more frequently in patients with rest angina than in other subgroups (72.34% and 27.66% respectively, P < 0.05), so did complex lesions and type C lesions (36.07% and 60.64% respectively, P < 0.05). More than half of the culprit lesions in post-infarction angina were subtotal or total occlusions (53.12%), being more frequently found in this than in other subgroups (P < 0.05). Most of the patients with Prinzmetal variant angina had mild coronary lesions only. Coronary thrombi were found in 10.45% of the 388 patients; they were more frequent in patients with post-infarction angina (20.00%) than in the subgroups of new onset effort angina, aggravated effort angina and Prinzmetal variant angina (4.26%, 7.53% and 0% respectively, P < 0.05). Coronary thrombi were also more frequent in patients with chest pain at rest (16.39%) than in the subgroups of new onset effort angina and Prinzmetal variant angina (P < 0.05). CONCLUSIONS: It is suggested that patients with angina at rest should be treated more intensively. Energetic anticoagulation treatment should be given to patients with post-infarction angina and angina at rest.

Adult↗

[Analysis of lobar pneumonic tuberculosis].

OBJECTIVE: To heighten the awareness of lobar pneumonic tuberculosis(or tuberculous pneumonia or acute pneumonic tuberculosis). METHOD: 10 cases with lobar pneumonic tuberculosis were reviewed. RESULT: All the patients showed acute onsets and 9 of them had a continuous high fever, and their WBC was not found higher than 10 x 10(9)/L. All of the patients' chest radiographs showed a consolidation in one or two lobars, and in 30% of the patients pleural effusions were found. Significant roent genographic changes could occur in short duration. All the patients were not sensitive to common antibiotics, and the shadow could enlarge in short time. Exudative foci could be absorbed shortly after antituberculosis chemotherapy, and no cavitation was found. CONCLUSION: An early transbroncho-lung biopsy (TBLB) and (or) brushing smear may be advantageous to early diagnosis and treatment of this illness.

Adolescent↗

[Head trauma and brain auditory evoked potentials].

The study investigated brain auditory evoked potentials (BAEP) in patients complaining auditory disturbances after head trauma. The results showed that the incidence of hearing loses was 57.5% and the rate of abnormality of BAEP is 33.75%. The types of the abnormalities of BAEP varied and were related with the position and severity of the head trauma. The types of the abnormalities manifested as loses of I-II waves, prolongation of V latency and I-V interlatency.

Adolescent↗

[Management of true extremity aneurysms: experience in 23 patients].

OBJECTIVE: To explore the etiologic feature and specificity of diagnosis and treatment in true aneurysms of the extremities. METHOD: 23 patients with true aneurysms of the extremities from January 1984 to September 1997 were retrospectively reviewed. RESULT: Of 30 true aneurysms of the extremities, multiple aneurysms were found in 7 patients (30.4%). The multiple aneurysms were diagnosed in the same time or in different time. 21 patients were treated by exclusion of aneurysm and replacement with autogenous saphenous vein or graft. CONCLUSION: Early diagnosis and treatment are recommended to prevent complications which can cause limb loss, and multiple aneurysms must be taken into account. Importance of arteriography should be stressed in the diagnosis of multiple aneurysms. Exclusion of aneurysm and autogenous saphenous vein reconstruction is the first choice of treatment, circulation of the operated extremities should be noticed and close follow-up is imperative to pay attention to the development of new aneurysms.

Adolescent↗

[The choice of intraocular lens before cataract extraction for cases with high myopia].

OBJECTIVE: To study the choice of diopter and size of optical portion of intraocular lens (IOL) before cataract extraction for cases with high myopia. METHODS: Extracapsular cataract extraction (ECCE) or phacoemulsification with IOL implantation was performed on 60 cases (94 eyes) with high myopia (axial length > 26mm). The posterior chamber IOL selected and inserted was the one with the diopter and size of the optical portion suitable for the recipient to have a postoperative low myopia and easy to be examined with an ophthalmoscope. RESULTS: The postoperative eyes were of low myopia, -2.07 +/- 1.95 D. The larger size of optical portion was more suitable for ocular fundus examination. Great care was taken for phacoemulsification for cataractous nucleus below III grade. CONCLUSIONS: For patients with axial myopia, the IOL implanted should create low myopia postoperatively. Larger optic size is better for fundus examination. Phacoemulsification can produce less astigmatism and damage, but the indication must be controlled strictly.

Adolescent↗

[Sulfation of polysaccharides isolated from Indocalamus tesselatus and their anticytopathic effect on human immunodeficiency virus type I].

For preparation of sulfated polysaccharides isolated from bamboo leaves (Indocalamus tesselatus) with chlorosulfonic acid-pyridine, the experimental conditions as the molar ratio of reactants and temperature and time of reaction were discussed. A homogeneous sulfation method with good yield of more than 80% was obtained and the sufur content was found to be 21.9%. Conformation change in sulfated polysaccharide with changes of intrinsic viscosity, polarimetery and CD spectra were found to be related to the negative charge. The polysaccharide sulfates were shown to have better activity to inhibit cytopathic effect of human immunodeficiency virus(HIV) infection than native polysaccharides. The effective concentration was 10 micrograms.ml-1 while the cytotoxic concentration was 2.5 mg.ml-1.

Antiviral Agents↗

Persistently exaggerated startle responses in rats treated with pyridostigmine bromide.

Troops in the Persian Gulf War have registered complaints consistent with CNS dysfunction that emerged after returning from the Gulf. A common experience among Persian Gulf War veterans was exposure to pyridostigmine bromide (PB) for prophylaxis against nerve gas exposure. To determine whether PB causes emergent CNS dysfunction, Wistar-Kyoto (WKY) and Sprague-Dawley (SD) rats were given PB for 7 consecutive days in their drinking water. The WKY, but not the SD, rats exhibited a delayed-onset, persistently exaggerated startle response. The WKY rats exhibited exaggerated startle responses that appeared 15 days after the end of PB treatment and were still evident 22 days after the end of treatment. Both the duration and the magnitude of the exaggerated startle responses were related to the dosage of PB. The PB-treated rats exhibited normal short-term and long-term habituation. However, exaggerated startle responses were related to the development of enhanced short-term sensitization. Treating the rats for a second time, 7 weeks after the end of the first PB treatment, induced an exaggerated startle response that appeared sooner and dissipated faster than was evident after the first PB treatment. Inasmuch as the WKY rat has inherently low butyrylcholinesterase activity, a scavenger for PB, these results suggest that prophylactic PB may influence CNS function in individuals with low butyrylcholinesterase activity. Elaboration of the factors that mediate enhanced sensitization in the WKY rat may provide insight into some of the complaints registered by veterans of the Persian Gulf War.

Animals↗

Molecular analysis of a P-type ATPase from Cryptosporidium parvum.

Eukaryotic P-type ATPases use energy to drive the transport of cations across membranes. A complete P-ATPase gene (CpATPase1) has been isolated from Cryptosporidium parvum, one of the opportunistic pathogens in AIDS patients. The complete gene encodes 1528 amino acids, predicting a protein of 169 kDa. A hydropathy profile of the protein suggested there are eight transmembrane domains (TM). Expression of the gene was confirmed both by Northern blot analysis and RT-PCR. A fragment of the gene has been expressed as a 49 kDa GST-fusion protein. This protein was used to produce rabbit antiserum and fluorescent labeling has localized the protein to the sporozoite apical and perinuclear regions. SDS-PAGE and Western blot analysis show a 160 kDa major protein, close to the predicted size. The protein shares greatest overall identity and similarity to a putative organellar Ca2+ P-ATPase described for Plasmodium falciparum. Unlike P. falciparum, but consistent with all genes so far isolated from C. parvum, the gene contains no introns. The Ca2+ P-ATPases from these two Apicomplexa are large and do not have motifs predicting calmodulin-binding.

Amino Acid Sequence↗

Specificity for activase is changed by a Pro-89 to Arg substitution in the large subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase.

Tobacco activase does not markedly facilitate the activation of ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco, EC 4.1.1. 39) from non-Solanaceae species, including the green alga Chlamydomonas reinhardtii. To examine the basis of this specificity, we focused on two exposed residues in the large subunit of Rubisco that are unique to the Solanaceae proteins. By employing in vitro mutagenesis and chloroplast transformation, P89R and K356Q substitutions were separately made in the Chlamydomonas enzyme to change these residues to those present in tobacco. Both mutants were indistinguishable from the wild type when grown with minimal medium in the light and contained wild-type levels of holoenzyme. Purified Rubisco was assessed for facilitated activation by spinach and tobacco activase. Both wild-type and K356Q Rubisco were similar in that spinach activase was much more effective than tobacco activase. In contrast, P89R Rubisco was not activated by spinach activase but was well activated by tobacco activase. Thus, the relative specificities of the spinach and tobacco activases for Chlamydomonas Rubisco were switched by changing a single residue at position 89. This result provides evidence for a site on the Rubisco holoenzyme that interacts directly with Rubisco activase.

Animals↗

Receptor induction regulates the synergistic effects of substance P with IL-1 and platelet-derived growth factor on the proliferation of bone marrow fibroblasts.

The neuropeptide substance P (SP) stimulates CFU in bone marrow (BM) cultures. Although the methylcellulose matrix used in these assays does not provide an appropriate substratum to support adherent-dependent cells, we have observed that cultures containing optimal SP (10(-8)-10(-10) M) develop confluent areas of reticular/fibroblastoid-like cells with CFUs predominantly localized within their vicinity. Characterization (cytochemical and immunofluorescence) of the reticular/fibroblastoid-like cells indicated that they were fibroblasts, the major constituent of the BM stroma. Hemopoietic effects by SP are mediated by the stroma that expresses SP receptors. We studied the effects of SP (10(-7)-10(-11) M) with suboptimal platelet-derived growth factor-BB (PDGF-BB; 5 ng/ml) and IL-1alpha (2 ng/ml), two fibrogenic cytokines, and also hemopoietic regulators. SP by itself and in synergy with either cytokine induced fibroblast proliferation. At optimum SP, IL-1alpha induced 1.6 times the proliferation of PDGF-BB (87 +/- 7 vs 55 +/- 5; n = 12; p < 0.05). The effects of SP were blunted by a specific neurokinin-1 antagonist. Scatchard analysis indicated that SP binds to BM fibroblasts with an approximate Kd of 5 nM. SP induced steady state mRNA for IL-1 receptor IL-1RI and PDGF-BB (PDGF-AR, PDGF-BR) receptors by 7.5-, 6.2-, and 10.5-fold, respectively. Their up-regulation may be partly responsible for the synergistic effects of SP and their ligands. Induction (3-fold) of neurokinin-1 mRNA by IL-1alpha compared with no induction by PDGF-BB may explain the preferred synergism between SP and IL-1alpha. This study indicates that induction of SP, IL-1alpha, and PDGF-BB receptors is important to their synergistic effects on BM fibroblast proliferation. These results bring new insights into stroma-mediated hemopoietic regulation.

Animals↗

Sp1 is a critical regulator of the Wilms' tumor-1 gene.

We performed deletion analysis of WT1-reporter constructs containing up to 24 kilobases of 5'-flanking and first intron WT1 sequence in stably transfected cultured cells as an unbiased approach to identify cis elements critical for WT1 transcription. Although not a tissue-specific element, a proximate 9-base pair CTC repeat accounted for approximately 80% of WT1 transcription in this assay. Enhancer activity of the element and mutated versions correlated completely with their ability to form a DNA-protein complex in gel shifts. Antibody supershift, oligonucleotide competition, and Southwestern studies indicated that the CTC-binding factor is the transcriptional activator Sp1. Sp1 binds the CTC repeat with an affinity, KD = 0.37 nM, at least as high as the consensus GC box. Similar CTC repeats are found in promoters of other growth-related genes. Because Sp1 is important for WT1 expression, we examined Sp1 immunohistochemistry in fetal and adult kidney. In a pattern that precedes that of WT1 message, Sp1 immunostaining was highest in uninduced mesenchyme, early tubules, developing podocytes, and mature glomeruli, but was minimal in mature proximal tubules. This work suggests abundant Sp1 may be a prerequisite for WT1 expression, and that Sp1 may have a wider role in nephrogenesis.

Animals↗

Progression of mouse buthionine sulfoximine cataracts in vitro is inhibited by thiols or ascorbate.

Mouse lens cultures were employed to study the progression of cataracts initiated by injection of buthionine sulfoximine, an inhibitor of glutathione (GSH) biosynthesis. Culture of lenses removed from untreated mice on postnatal day 7, for 48 hr in the presence of 4 mm BSO, resulted in only limited cataractous changes. To enable substantial progression of cataracts in vitro, it was therefore necessary to pretreat the mice with BSO prior to lens culture. A single injection of BSO (4 nmol mg-1 lens), administered on day 7, resulted in >90% depletion of lens GSH within 3 days, but no visible cataractous changes. The clear lenses were incubated for 29+/-1 hr at 37 degrees C in Medium HL-1, supplemented with EGF, insulin and Ca2+, in the presence or absence of BSO, and were scored for cataract development by previously described criteria. In the absence of BSO, only 4 of 10 lenses developed large opacities. However, in the presence of 4 mm BSO, 40 out of 45 experimental lenses developed opacities affecting at least 50% of the lens visual field and were scored as stages 1C-4, depending upon the extent and density of the cataracts. In addition, three lenses had opacities involving 20-50% of the field (stage 1B). By contrast, less than 10% of lenses from untreated mice incubated in the absence of BSO developed opacities. The cataracts developed in 4 mm BSO were accompanied by reduction of lens glutathione levels to <0.010 nmol mg-1 lens. They were almost completely prevented by 1 mm ascorbate, 2 mm GSH, 2 mm GSH monoethyl ester and 2 mm cysteamine. GSH and GSH ester maintained lens glutathione content between 0.1 and 0.2 nmol mg-1 in the presence of BSO, whereas ascorbate did not prevent near-total GSH depletion. The prevention of cataracts by thiols and ascorbate was confirmed by lens Na/K ratios not significantly different from those in control lenses. The above combination of GSH depletion in vivo by a single injection of BSO, followed 3 days later with lens culture in the presence of BSO, may yield a useful system to elucidate and control the biochemical mechanisms involved in oxidative cataract induction by this GSH-depleting agent.

Animals↗

Effect of selenium supplementation on mice infected with LP-BM5 MuLV, a murine AIDS model.

LP-BM5 Murine leukemia virus (MuLV) infection of C57BL/6 mice develop a disease that has many features in common with human acquired immunodeficiency syndrome (AIDS), in particular abnormal lymphoproliferation and severe immunodeficiency. Thus, this MAIDS model may be useful for evaluation of potent antirival agents in vivo. Deficiency in antioxidant micronutrients such as selenium, zinc, and glutathione have been observed in AIDs and AIDS-related complex (ARC) patients. In the present study, the MAIDS model was used to evaluate immunological and oxidative effect of Se as sodium selenite. Results indicated that Se treatment 0.1 mg/kg/d (p.o.) inhibited splenomegaly and sera IgG elevation effectively. In addition to abnormal immunity, oxidative imbalance possibly existed in MAIDS model, as lipid peroxide increased significantly in spleen and whole blood glutathione peroxidase (GSH-Px) activity decreased markedly. Se supplementation had good protective effect.

Animals↗

Polyamine biosynthesis in Cryptosporidium parvum and its implications for chemotherapy.

This study demonstrates that polyamine biosynthesis in Cryptosporidium parvum occurs via a pathway chiefly found in plants and some bacteria. The lead enzyme of this pathway, arginine decarboxylase (ADC) was sensitive to the specific, irreversible inhibitor DL-alpha-difluoromethyl-arginine (IC50 30 microM), and intracellular growth of C. parvum was significantly reduced by inhibitors of ADC. No activity was detected using ornithine as substrate, and the irreversible inhibitor of ornithine decarboxylase, DL-alpha-difluoromethyl-ornithine, had no effect upon ADC activity or upon growth of the parasite. Back-conversion of spermine to spermidine and putrescine via spermidine:spermine-N1-acetyltransferase (SSAT) was also detected. Compounds such as his(ethyl)norspermine, which have been demonstrated to down-regulate SSAT activity in tumor cells, were synergistic in the inhibition of growth when used in combination with inhibitors of the forward pathway. Thus, C. parvum differs fundamentally in its polyamine metabolism from the majority of eukaryotes, including humans. Such differences indicate that polyamine metabolism may serve as a chemotherapeutic target in this organism.

AIDS-Related Opportunistic Infections↗

Synthesis and purification of NB1-palmitoyl insulin.

A procedure for synthesizing NB1-palmitoyl insulin for incorporation into liposomes for targeting to hepatocytes was developed. The amino group of the first amino acid phenylalanine on the B chain (B1) of insulin was selected for conjugation with palmitic acid in anticipation that its binding to the insulin receptor would be preserved. Two other free amino groups present in insulin, the first amino acid glycine on the A chain (A1) and the 29th amino acid lysine on the B chain (B29), were first protected with a t-butoxycarbonyloxy (t-Boc) group to yield NA1, B29-di-(t-Boc) insulin. The identity of this di-(t-Boc) insulin was confirmed by amino acid analysis as well as by enzyme hydrolysis coupled with matrix-assisted laser-desorption time of flight mass spectrometry (MALDI-TOF MS). NA1,B29-Di-(t-Boc) insulin was then reacted with the N-hydroxysuccinimide ester of palmitic acid, followed by deblocking the t-Boc groups, to yield NB1-palmitoyl insulin, the structure of which was further confirmed by MALDI-TOF MS analysis. NB1-palmitoyl insulin was found to interact with the insulin receptor on fat cells, thereby catalyzing the conversion of [14C]glucose into lipids, at reduced efficiency (30-40%).

Animals↗

Adenovirus-mediated beta-galactosidase gene delivery to the liver leads to protein deposition in kidney glomeruli.

The many cell types of the kidney, precisely arranged, allow this organ to perform its complex physiologic functions. However, this architectural complexity makes gene transfer into the kidney difficult. One approach to delivering a therapeutic protein to the kidney is to transfer a gene to a non-renal tissue. Release of the protein into the circulation might then result in deposition in the kidney, if the protein has the appropriate molecular properties. In this study, we found that parenterally administered replication deficient adenovirus carrying the beta-galactosidase gene resulted in intense beta-galactosidase gene expression in hepatocytes. As a result of immune attack on transduced hepatocytes, beta-galactosidase protein from these cells is released into the circulation, transported, and deposited almost exclusively in kidney glomeruli. Intense beta-galactosidase activity was noted in both kidneys with a peak at two weeks following viral administration, concurrent with loss of beta-galactosidase positive hepatocytes. Consistent with our hypothesis of protein transfer, no beta-galactosidase mRNA was detected in glomeruli. Moreover, systemically administered protein generated similar glomerular beta-galactosidase activity. Finally, co-administration of murine CTLA4 Ig, an immunomodulator of T cell activation, with the adenovirus protected infected hepatocytes and markedly diminished glomerular beta-galactosidase activity. Collectively, these findings suggest that a therapeutic protein can be "targeted" to the renal glomerulus, utilizing the liver as a gene transfer organ.

Abatacept↗

Beta 1,4 N-acetylgalactosaminyltransferase (GM2/GD2/GA2 synthase) forms homodimers in the endoplasmic reticulum: a strategy to test for dimerization of Golgi membrane proteins.

Many Golgi membrane-bound glycosyltransferases exist as intermolecular disulfide bonded species, some of which have been demonstrated to be homodimers. Evidence for homodimer formation has come primarily from radiation inactivation experiments. We utilized an alternative strategy to test for homodimer formation of the cloned beta 1,4 N-acetylgalactosaminyltransferase (GalNAcT) responsible for synthesis of the glycosphingolipids GM2, GD2, and GA2. We stably transfected CHO cells with myc epitopetagged GalNAcT, which localizes primarily to the Golgi, and a hemagglutinin (HA) epitope-tagged GalNAcT fusion protein in which the cytoplasmic domain of GalNAcT was replaced by an ER retention signal. We then sought evidence for dimer formation between the two forms of GalNAcT. Immunoprecipitation with anti-myc or anti-HA co-immunoprecipitated the HA-tagged form or the myc-tagged form, respectively, providing evidence for the physical association of the two forms of GalNAcT. As a result of this association, GalNAcT/myc increased in the ER as demonstrated by Western blots and immunofluorescence. The rapid formation of dimers provided further evidence for dimer formation occurring in the ER. In summary, these results demonstrate that GalNAcT forms homodimers as a result of intermolecular disulfide bond formation in the ER. Furthermore, this ER motif strategy is potentially useful for demonstrating homodimer formation of other Golgi enzymes.

Animals↗