Biomedical subjects

L Zhou

Publications and source records attributed to L Zhou.

At least 469 records · Page 26Linked to original sources

PubMed1996

[Phase I clinical study of a new anticancer drug boanmycin].

From August 1993 to March 1994, 36 patients were enrolled for a phase I study of Boanmycin (Bleomycin A6) a new anticancer drug to determine it toxicity and maximal dose. Of the 36 cases, 16 were male and 20 female, age 20-62. Dose escalation was performed if a minimum of threed patients were fully evaluable for toxicity (2 weeks following drug administration) and if severe or life-threatening toxicity had not occurred. Dose of Boanmycin were escalated from 1 mg (0.5-0.7 mg/m2) to 12 mg(6.7-7.5 mg/m2) i. m. three times every week for two weeks. Surveillance of serum concentration of Boanmycin was conducted in six cases by microbiological analysis, and the pharmacokinetics parameters were obtained. Phase I study of Boanmycin showed that Boanmycin had no myelosuppression and cardiac toxicity, and its major adverse reactions were fever, gastrointestinal reactions and hardening at injection (by i. m. route). Rather than dose-related, fever was individual-related. There were mild myalgia, alopecia, skin rash, pigmentation in some patients. All adverse reactions resolved after discontinuation of therapy. There was no Boanmycin-related lethal complication, and the maximum tolerated dose was not obtainable. If patients have renal or lung disease, Boanmycin aggravate their renal and lung functions. Therefore we recommend that dose of Boanmycin for phase I clinical trial should be is 8-10 mg(5-6 mg/m2) i m or iv (iv can decrease local side effect) two-three times per week.

Adult↗

PubMed1996

[Molecular weight determination and protein analysis of GCF-5 antigens of giant cell tumor of bone].

In order to understand the tumor antigen(s) of giant cell tumor of bone (GCT), monoclonal antibody GCF-5 developed in this laboratory was employed. GCF-5 reacted specifically against the tumor cell associated antigens of GCT. The membrane proteins of tumor cell were extracted by high concentration of SDS, followed by a series of treatment processes, including SDS-PAGE, western blotting and some staining methods, such as Periodic-Schiff for glycoprotein and oil red O for lipoprotein. The molecular weight and chemical characteristics of GCF-5 antigens were analysed. The preliminary results indicated that the main GCF-5 antigens were two glycoproteinis containing few saccharide chains, one of which was 13.5KD and the other 17.4KD.

Antigens, Neoplasm↗

PubMed1996

[Etoposide combination chemotherapy for malignant lymphoma: a report of 91 cases].

From August 1984 to August 1994 ninety-one caese of malignant lymphoma (NHL 84 casese, HD 7 cases) were treated with Etoposide (VP-16) combinationn chemotherapy. In 70 evaluable patients, 18 achieved CR, 35 PR, total response rate was 75.7%, response time (RT) 1-79 months, medium response time (MRT) 9 months, survival time (ST) 2-79 months, medium survival time (MST) 12 months. The therapeutic efficacy was better than VP-16 alone. The major side effects were myelosuppression and gastrointestinal toxicity. In COPEP, CHEP, PEP and IEP regimens, best result was seen in COPEP (CTX + VCR + PYM + VP-16 + PDN), with a response rate of 93%. Authors suggest that COPEP protocol could be the first line treatment for patients with malignant lymphoma who did not tolerate anthracycline drugs and the second line treatment for anthracycline-resistant patients.

Adolescent↗

PubMed1996

[Clinical study of the pattern of lymphnode metastasis in carcinoma of esophagus: an analysis of 200 cases].

To study the pattern of lymphnode metastasis in carcinoma of the esophagus, 200 cases of resected esophageal cancer specimens were carefully examined pathologically. Lymphnode metastasis, its pathway and extent in relation to pathological changes were analyzed. Lymphnode metastasis was mainly regional and extended vertically in both directions. Leaping-over metastasis was another feature. The deeper invasion by the tumor, the higher frequencies of metastasis development, and vice versa. However, leaping-over metastasis was more likely to occur where tumor invasion was less severe. Owing to the high frequency of lymphnode metastasis in the superior mediastinum and the widely spanned leaping-over metastases, an operative approach by three incisions through right thoracotomy with excision of the whole segment of esophagus and anastomosis at cervical region was recommended, in order to dissect lymphnodes in the cervical, thoracic and abdominal regions and to leave less or no metastatic lymphnodes behind.

Adult↗

PubMed1996

[The practical application on the numbers of control in 1:R matched case-control study].

We applied the data base of a screening program for colorectal cancer in the general population of Jiashan county, Zhejiang province to verify the theory of Pitman Efficiency in 1:R matched case-control study. Forty one detected cases of colorectal cancer were matched with normal controls as 1:R (R from 1 to 50) who were randomly selected from the screened population including 62,667 subjects. Results showed that the number of risk factors with statistical significance and its coincidence rate with results of 1:50 match were increased along with the increasing of R value; meanwhile the trends of standard deviation with 1:R over 1:50 weakened and the stability of results increased accordingly. The change of these values, however, reached their plateau when R > 4. The authors suggest that when taking consideration of sensitivity and stability of matched study, 1:4 of 1:5 ratio might be the most suitable case-control match, particularly when the resources are limited or the study has a exploratory nature.

Case-Control Studies↗

PubMed1996

[Effect of motilin on contractile activity of isolated smooth muscle of stomach].

The present study was conducted to investigate the contractile effect of motilin on isolated smooth muscle cells of rat stomach. The results were as follows: (1) Motilin elicited contraction of gastric smooth muscle cells in a dose-dependent manner from 10(-11) to 10(-10) mol. (2) At concentration of 10(-10) mol, the contractile response of antral smooth muscle cells exceeded that of the body and pyrous muscle cells. (3) Anti-motilin serum could completely eliminate the stimulatory effect of motilin, which was not affected by atropine, TTX, cimetidine or loxiglumide. (4) TMB-8, an inhibitor of intracellular Ca2+ release, could also suppress completely the motilin effect. The above results suggested that the motilin effect on isolated gastric smooth muscle cells is a direct one, being mediated by highly specific motilin receptors in connection with the event of intracellular release of Ca2+.

Animals↗

PubMed1996

[An ultrastructural pathological study of pterygium].

OBJECTIVE: To study the ultrastructural changes of pterygium. METHOD: The pathological ultrastructure of pterygium was studied by Hu-12A transmission electron microscopy in 14 specimens. RESULTS: The result indicated that normal and abnormal elastic fibers and collagenous fibers existed in the pterygium. As hyperplastic fibers intruded into the corneal subepithelium, Bowman's membrane was broken. To a certain extent, blood vessel multiplication and degeneration were found in the pterygium. One of the important factors was blood vessel multiplication and degeneration which affected the occurrence and development of pterygium. CONCLUSION: Multiplication and degeneration of elastic and collagenous fibers were the prominent pathological changes, and the pre-elastic fibers and denatured elastic fibers were the main compositions of pterygium.

Adult↗

PubMed1995

Pulmonary malformation in transgenic mice expressing human keratinocyte growth factor in the lung.

Expression of human keratinocyte growth factor (KGF/FGF-7) was directed to epithelial cells of the developing embryonic lung of transgenic mice disrupting normal pulmonary morphogenesis during the pseudoglandular stage of development. By embryonic day 15.5(E15.5), lungs of transgenic surfactant protein C (SP-C)-KGF mice resembled those of humans with pulmonary cystadenoma. Lungs were cystic, filling the thoracic cavity, and were composed of numerous dilated saccules lined with glycogen-containing columnar epithelial cells. The normal distribution of SP-C proprotein in the distal regions of respiratory tubules was disrupted. Columnar epithelial cells lining the papillary structures stained variably and weakly for this distal respiratory cell marker. Mesenchymal components were preserved in the transgenic mouse lungs, yet the architectural relationship of the epithelium to the mesenchyme was altered. SP-C-KGF transgenic mice failed to survive gestation to term, dying before E17.5. Culturing mouse fetal lung explants in the presence of recombinant human KGF also disrupted branching morphogenesis and resulted in similar cystic malformation of the lung. Thus, it appears that precise temporal and spatial expression of KGF is likely to play a crucial role in the control of branching morphogenesis during fetal lung development.

Animals↗

PubMed1995

Expression and purification of the light chain of botulinum neurotoxin A: a single mutation abolishes its cleavage of SNAP-25 and neurotoxicity after reconstitution with the heavy chain.

Botulinum neurotoxin type A (BoNT/A) selectively and irreversibly inhibits acetylcholine release from peripheral nerve endings. While the toxin's heavy (H) chain contributes to neuronal binding and internalization, its light (L) chain is a Zn(2+)-dependent endoprotease that intracellularly cleaves synaptosomal-associated protein of M(r) = 25 kDa (SNAP-25). For research and clinical exploitation of this uniquely-acting neurotoxin, recombinant wild-type L chain was produced together with a mutant in which His227 in the Zn(2+)-binding motif was substituted by Tyr. The PCR-amplified wild-type and mutant L chain genes were cloned, fused to the gene for maltose-binding protein, and expressed at high levels in Escherichia coli. The soluble fusion proteins were purified using amylose affinity chromatography, and, after factor Xa cleavage, the free L chains were isolated. The wild-type was shown to proteolyze SNAP-25 at a rate approaching that of the native chain while the mutant was inactive. Reconstitution of the pure wild-type L chain with native homogeneous H chain yielded a disulfide-linked dichain form that inhibited neuromuscular transmission in vitro and produced the symptoms of botulism in vivo. After reconstitution with the H chain, the Tyr227 mutant L chain failed to show any neuroparalytic activity in either of these assays. This methodology allows, for the first time, routine preparation of recombinant forms of the L chain that are needed to decipher the molecular details of its interaction with substrate and, thereby, assist the design of effective inhibitors.(ABSTRACT TRUNCATED AT 250 WORDS)

ATP-Binding Cassette Transporters↗

PubMed1995

Mutation of the carboxy terminal zinc finger of E. coli isoleucyl-tRNA synthetase alters zinc binding and aminoacylation activity.

Escherichia coli isoleucyl-tRNA synthetase has been shown to contain two enzyme-bound zinc atoms per polypeptide chain. To investigate the structural and functional significance of the C-terminal enzyme-bound zinc, mutagenesis was used to alter Cys 922 to Ser [IleRS(C922S)] and to replace Cys 922 through Ala 939 with a 33 amino acid peptide unable to bind zinc (AIleRS). Both IleRS(C922S) and AIleRS were found to contain only a single enzyme-bound zinc per polypeptide chain. Substitution of Co2+ for Zn2+ in IleRS(C922S) gave a visible spectrum characteristic of that expected for a single tetrahedrally coordinated enzyme-bound Co2+ atom. Little or no effect on the Km values for ATP or Ile and only a 5 fold reduction of the (kcat/Km)Ile was observed for IleRS(C922S) and AIleRS in the isoleucine-dependent ATP-pyrophosphate exchange reaction. In the tRNA-dependent aminoacylation reaction, Km values for tRNA(Ile) were only slightly affected in the mutant proteins. However, kcat/Km values were decreased approximately 200 and 2500 fold for IleRS(C922S) and AIleRS, respectively. These results suggest that both the C-terminal enzyme-bound zinc and the C-terminal peptide play important roles in aminoacylation of tRNA(Ile).

Amino Acid Sequence↗

PubMed1995

Characterization of a novel oligodendrocyte cell surface molecule.

Cell-type-specific reagents have proven useful in the analysis of central nervous system (CNS) development and function. Most markers of oligodendrocytes are components of myelin sheath, which in the CNS is the specific product of oligodendrocytes. We have isolated a novel monoclonal antibody termed 2B10 which was raised against embryonic rat spinal cord tissue. In adult rat cerebrum, cerebellum, and spinal cord, 2B10 immunoreactivity is predominantly localized in white matter. 2B10 immunoreactivity is absent from peripheral nerve, suggesting that in the nervous system the 2B10 antigen is restricted to the CNS. Dissociated cell culture studies indicate that 2B10 labels a cell surface molecule, and its cellular distribution is coincident with O1 and myelin basic protein-positive oligodendrocytes. By contrast, 2B10 does not label GFAP-positive astrocytes. These data suggest that in the CNS the 2B10 antigen is expressed specifically on oligodendrocytes. Biochemical analysis indicates that 2B10 recognizes a protein with an apparent molecular weight of approximately 79,000 in reducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Developmentally, 2B10 immunoreactivity is detectable in rat spinal cord at as early as embryonic day 14. The relative abundance of this molecule decreases during myelination, but is maintained at a sustained level throughout adulthood. The 2B10 antigen appears not to be a myelin-associated protein since it is not detected in purified myelin fractions. 2B10 immunoreactivity is not detectable in extracts of rat sciatic nerve, heart, kidney, muscle, and skin, but is detectable in extracts of spleen and thymus. These data suggest that the 2B10 antigen is a novel cell surface molecule that is expressed on oligodendrocyte lineage cells throughout development.

Animals↗

PubMed1995

Major groove (R)-alpha-(N6-adenyl)styrene oxide adducts in an oligodeoxynucleotide containing the human N-ras codon 61 sequence: conformations of the R(61,2) and R(61,3) sequence isomers from 1H NMR.

Conformations of (R)-alpha-(N6-adenyl)styrene oxide adducts at positions X6 in d(CGGACXAGAAG).d(CTTCTTGTCCG) and X7 in d(CGGACAXGAAG).d(CTTCTTGTCCG), incorporating codons 60, 61 (underlined), and 62 of the human n-ras protooncogene, were refined from 1H NMR data. These were the R(61,2) and R(61,3) adducts. Chemical shift perturbations were in the 5'-direction from the sites of adduction; large changes were observed for C5 H5 and H6 in the R(61,2) adduct. The styrene moieties were only partially defined by NOE data. Spectral overlap, particularly for the R(61,2) adduct, prevented complete assignments of the aromatic resonances; likewise, there were insufficient data to orient the CH2OH moieties. Ring flips were slow on the NMR time scale. For the R(61,2) adduct 260 restraints were obtained from NOE data at three mixing times using relaxation matrix analysis; for the R(61,3) adduct 230 restraints were obtained. Structures emergent from molecular dynamics/simulated annealing for the R(61,2) adduct converged to average and maximum pairwise rms differences of 1.3 and 1.7 A, respectively, while those for the R(61,3) adduct converged to average and maximum pairwise rms differences of 1.2 and 1.6 A. Sixth root residual indices of 7.5 and 6.8 x 10(-2) were measured between the refined structures and NOE intensities using relaxation matrix calculations for the R(61,2) and R(61,3) adducts, respectively. The styrene rings were in the 5'-direction from the lesion sites in the major groove. The preferred orientation calculated for the R(61,2) adduct placed the styrene ring edgewise and approximately orthogonal to C5, while that calculated for the R(61,3) duplex had the styrene ring approximately orthogonal to the major groove edges of base pairs A6.T17 and R-SOA7.T16.

Adenine↗

PubMed1995

Binding of prothrombin to chyle chylomicrons: effects of temperature and calcium ions, and role of surface phospholipids.

The ability of chyle chylomicrons to bind prothrombin has been studied. Rat chyle chylomicrons were incubated with human 125I-prothrombin and binding was examined by separating the chylomicrons from free 125-I-prothrombin by density-gradient ultracentrifugation, and by gel filtration on Sepharose CL-2B. A significant binding of prothrombin to chyle chylomicrons occurred. The complex formation was calcium dependent, and decreased markedly when the temperature was lowered from 37 degrees C to 20 degrees C and when PH was raised above 8. The time course for the binding at 37 degrees C in presence of 2 mmol/L CaCl2 exhibited an initial lag phase at about 10 minutes. Thereafter most of the binding occurred within 30 minutes. Bound prothrombin could not be removed from chyle chylomicrons by treatment with EDTA, suggesting that this binding is not a simple Ca2+ dependent association between prothrombin and chyle chylomicrons. Inclusion of 1% purified human serum albumin caused a 50% decrease in binding, half of which was reversed by increasing the Ca2+ ion concentration. Addition of pancreatic phospholipase A2 (PLA2) in doses sufficient to hydrolyze more than 95% of the phosphatidylethanolamine (PE) and 37% of the phosphatidylcholine (PC) decreased the binding by 50%. Doses of PLA2 that hydrolyze more than 95% of the phosphatidylethanolamine (PE) and 37% of the phosphatidylcholine (PC) decreased the binding by 50%. Doses of PLA2 that hydrolyzed 60-80% of (PE and 4-10% of the PC decreased the binding by only 7-15%. It is suggested that the binding of prothrombin to chyle chylomicrons is in part mediated by negatively charged phospholipids of the chylomicron surface, although a specific role of the PE could not be demonstrated.

Animals↗

PubMed1995

Crystallization and preliminary X-ray analysis of two density populations of feline calicivirus.

Two density populations of full-size feline calicivirus (FCV), the intact infectious particles (P(H)) and the empty capsids (P(L)), have been crystallized using the hanging-drop method. Exposed to high-intensity synchrotron radiation, P(H) and P(L) crystals were shown to diffract X-rays to about 3.0 and 5.5 A resolution, respectively. The P(H) crystal belongs to an orthorhombic crystal system with unit-cell dimensions a = 889.0, b = 995.0, c = 436.6 A. Based on the V(M) value (3.4 A(3) Da(-l)), it was estimated that one crystallographic asymmetric unit of P(H) crystals contains the unique content of an entire virus particle, not necessarily from the same particle. This implies the presence of 60-fold non-crystallographic redundancy. The particle orientation was obtained from a locked rotation function.

Journal Article↗

PubMed1995

Programmed cell death in the Drosophila central nervous system midline.

BACKGROUND: During the development of the central nervous system, large numbers of cells die by programmed cell death. This process requires the activity of specific gene products and subserves functions that include regulating the sizes of interacting cell populations and removing cells that provide transient functions. Resolution of programmed cell death often involves the elimination of dying cell corpses by phagocytic macrophages. In Drosophila, the reaper gene plays a crucial role in mediating programmed cell death; chromosomal deficiencies which remove reaper result in an absence of programmed cell death. We have used a reaper-deficiency mutant strain Df(3R)H99 (or H99), in conjunction with strains containing cell-type-specific markers, to examine the role of programmed cell death in differentiation of the embryonic central nervous system midline. RESULTS: Midline cell death was identified both by the presence of excess midline cells in H99 mutants and by the engulfment of dying midline cells by macrophages in wild-type embryos. These developmental deaths are lineage-specific: prominent midline glial death was observed, while little if any death was detected among the ventral unpaired median neurons. Examination of H99 mutants indicates that cell death is not required for the formation of macrophage precursors, or for their subsequent migration throughout the embryo; however, in the absence of dying cells, macrophage precursors do not exhibit morphological differentiation or phagocytosis. In both wild-type and H99 mutant embryos, a subset of macrophages migrate along the ventral midline. This midline migration is not observed in single-minded mutants, in which ventral midline cells fail to develop. CONCLUSIONS: Programmed cell death plays a crucial role in the development of the central nervous system midline, and dying midline cells are rapidly eliminated by phagocytic macrophages. It seems that the generation of engulfment signals in cells undergoing programmed cell death is downstream of reaper gene function, and that central nervous system midline and/or ventral epidermal cells provide directional cues for migrating macrophages.

Animals↗

PubMed1995

Gonadal steroid hormones upregulate medial preoptic mu-opioid receptors in the rat.

The density of mu-opioid receptors is dependent upon the levels of gonadal steroid hormones in the medial preoptic area of ovariectomized female rats. Because the region containing these cyclical mu-opioid receptors is relatively small, autoradiographic analysis of the binding of a saturating concentration of mu-selective radioligand was used to determine whether hormone treatment affects maximal binding capacity of these receptors. The results reveal that gonadal steroid hormones upregulate mu-opioid receptor binding capacity specifically in the medial preoptic area 27 h later, without affecting binding in adjacent brain regions. This suggests that hormones induce a functional increase of medial preoptic area mu-opioid receptors which could serve to regulate reproductive activities.

Animals↗

PubMed1995

Role of platelet factor Xa in chylomicron-prothrombin complexes induced platelet activation.

The effects of chylomicron-prothrombin complexes on platelet activation, including platelet aggregation, serotonin release, arachidonic acid release and increases of platelet cytosolic [Ca2+]i were examined. Furthermore the role of platelet factor Xa on the conversion of chylomicron bound prothrombin to thrombin was studied by using a synthetic inhibitor of factor Xa, TenStop. The chylomicron-prothrombin complexes could induce platelet aggregation and enhance the platelet serotonin release and arachidonic acid release in contrast to native chyle chylomicrons. An increase of platelet [Ca2+]i was observed during incubation with chylomicron-prothrombin complexes. TenStop inhibited platelet aggregation and serotonin release that were induced by chylomicron-prothrombin complexes in a dose-dependent manner, whereas the TenStop itself did not inhibit the platelet aggregation induced by thrombin and collagen. It is concluded that platelet activation induced by chylomicron-prothrombin complexes is related to the platelet factor Xa that could be the key factor in the conversion of chylomicron bound prothrombin to thrombin.

Animals↗

PubMed1995

Competence for genetic transformation in Streptococcus pneumoniae: organization of a regulatory locus with homology to two lactococcin A secretion genes.

Regulation of competence for genetic transformation in Streptococcus pneumoniae involves the comAB locus and a small extracellular protein, the competence factor (CF). The comA or comB mutations block both spontaneous competence induction and elaboration of CF, yet permit induction of competence by added CF and subsequent transformation at normal levels. Sequence and genetic studies showed that the com locus comprised the comA and comB genes, encoding 77- and 50-kDa proteins, respectively, and demonstrated that they were closely flanked by genes and DNA not required for competence regulation. In-frame deletion of comA demonstrated that the translation product of this gene is required for normal competence regulation; deletion-replacement mutations showed that no com gene lay in the 0.2-kb gap between comB and purC or within 2.5 kb upstream from comA. Strong sequence similarities (51-59% identities) showed that ComA and the proteins, PdcD and LcnC, which act in the secretion of pediocin A-1 and lactococcin A, respectively, form a subfamily within the large ABC-transporter protein family. ComB was found to be homologous to a single known protein, LcnD, required for secretion of the peptide antibiotic lactococcin A. Thus, the comAB locus displays homology to two lactococcin A secretion genes, but is devoid of additional linked com genes. The results suggest that the mechanism for CF production is similar to that for the small peptide bacteriocins, lactococcin A and pediocin A-1, but that its genetic organization is unusual in being split into at least two separate operons.

ATP-Binding Cassette Transporters↗