[Treatment of infected deciduous root canal with Samyan (traditional Chinese medicine)paste: Clinical analysis]
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Journal Article↗
Biomedical subjects
C Qian
Publications and source records attributed to C Qian.
A new serine-protease fold revealed by the crystal structure of human cytomegalovirus protease.
Human cytomegalovirus (hCMV), a herpesvirus, infects up to 70% of the general population in the United States and can cause morbidity and mortality in immunosuppressed individuals (organ-transplant recipients and AIDS patients) and congenitally infected newborns. hCMV protease is essential for the production of mature infectious virions, as it performs proteolytic processing near the carboxy terminus (M-site) of the viral assembly protein precursor. hCMV protease is a serine protease, although it has little homology to other clans of serine proteases. Here we report the crystal structure of hCMV protease at 2.0 angstroms resolution, and show that it possesses a new polypeptide backbone fold. Ser 132 and His 63 are found in close proximity in the active site, confirming earlier biochemical and mutagenesis studies. The structure suggests that the third member of the triad is probably His 157. A dimer of the protease with an extensive interface is found in the crystal structure. This structure information will help in the design and optimization of inhibitors against herpesvirus proteases.
Crystallography, X-Ray↗
Tumor necrosis factor alpha gene expression and the response to interferon in chronic hepatitis C.
Tumor necrosis factor alpha (TNF-alpha) is a cytokine with pleiotropic properties that is induced in a variety of pathological situations including viral infections. In this work, we analyzed the expression of TNF-alpha gene in patients with chronic hepatitis C. Serum TNF-alpha levels were found to be elevated in all chronic hepatitis C patients including those cases presenting sustained biochemical remission of the disease after interferon therapy. Untreated patients with chronic hepatitis C showed increased TNF-alpha messenger RNA (mRNA) levels in the liver and mononuclear cells as compared with healthy controls. After completion of treatment with interferon, patients experiencing sustained complete response showed values of TNF-alpha mRNA, both in the liver and in peripheral mononuclear cells, within the normal range, significantly lower than patients who did not respond to interferon and than those with complete response who relapsed after interferon withdrawal. Pretreatment values of TNF-alpha mRNA were lower in long-term responders to interferon than in cases who failed to respond to the treatment. Values of TNF-alpha mRNA in the liver or in mononuclear cells were higher in specimens with positive hepatitis C virus (HCV) RNA than in those samples where the virus was undetectable. Neither the intensity of the liver damage nor the amount of HCV RNA in serum or in cells showed correlation with the levels of TNF-alpha transcripts in peripheral mononuclear cells but it was found that high TNF-alpha values were associated with genotype 1b. In conclusion, there is an enhanced expression of TNF-alpha in HCV infection. High levels of this cytokine may play a role in the resistance to interferon therapy.
Adult↗
Does assisted hatching improve implantation rates after in vitro fertilization or intracytoplasmic sperm injection in all patients? A prospective randomized study.
PURPOSE: Preliminary data from some research centers indicate that assisted hatching might be of value to increase embryo implantation rate in the human, at least in selected cases. It is not clear, however, whether this technique would be of benefit for all patients undergoing an embryo transfer. We therefore performed a prospective randomized study to evaluate the effect of assisted hatching on the implantation rate in our in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) program. METHODS: In total, 120 couples undergoing an embryo transfer were randomized between two groups: in one group no assisted hatching was performed (AH-), whereas in the other group the embryos selected for transfer were subjected to partial zona dissection (PZD) immediately prior to the transfer (AH+). Using a computer-generated minimization procedure, patients were allocated to one of the two groups according to four pre-selected criteria: the number of embryos transferred, the cumulative score of transferred embryos, the age of the patient, and the use of ICSI. RESULTS: Pregnancy and implantation rates in the AH+ and AH- groups were, respectively, 42.1 versus 38.1% and 17.9 versus 17.1%. CONCLUSIONS: From our data we conclude that assisted hatching through partial zona dissection prior to embryo transfer does not improve pregnancy and embryo implantation rates in unselected patients undergoing IVF or ICSI.
Adult↗
Mutant fibrillin-1 monomers lacking EGF-like domains disrupt microfibril assembly and cause severe marfan syndrome.
Marfan syndrome (MFS), a heritable connective tissue disorder, is caused by mutations in the gene coding for fibrillin-1 (FBN1), an extracellular matrix protein. One of the three major categories of FBN1 mutations involves exon-skipping. To rapidly detect such mutations, we developed a long RT-PCR method. Either three segments covering the entire FBN1 coding sequence or a single 8.9 kb FBN1 coding segment were amplified from reverse-transcribed total fibroblast RNA. Restriction fragment patterns of these RT-PCR products were compared and abnormal fragments were directly sequenced. Six exon-skipping mutations were identified in a panel of 60 MFS probands. All skipped exons encode calcium binding epidermal growth factor (EGF)-like domains and maintain the reading frame. In five probands, exon-skipping was due to point mutations in splice site sequences, and one had a 6 bp deletion in a donor splice site. Pulse-chase analysis of labelled fibrillin protein revealed normal levels of synthesis but significantly reduced matrix deposition. This dominant-negative effect of the mutant monomers is considered in the light of current models of fibrillin assembly. Probands with this type of FBN1 mutation include the most severe forms of MFS, such as neonatally lethal presentations.
Epidermal Growth Factor↗
Oocyte morphology does not correlate with fertilization rate and embryo quality after intracytoplasmic sperm injection.
The fertilization rates and further development of 528 human metaphase II oocytes directly injected by a single spermatozoon were analysed with respect to their morphological features at the light microscopy level at the time of retrieval. The deviations of oocyte morphology which were most frequently observed, after removal of cumulus cells, were dark incorporations, dark zona pellucida, large perivitelline space, spots, vacuoles, refractile bodies and irregular shape. These deviations correlated neither with the fertilization rate nor with the embryo quality score, as compared to 'ideal' oocytes. Since the majority of oocytes displayed deviations from the 'ideal' morphotype but were still fertilized and developed in culture at a normal rate, they were probably as normal as 'ideal' oocytes. Since some of these morphotypes, such as refractile bodies, have been shown to be associated with failure of fertilization, it seems that intracytoplasmic sperm injection may be an appropriate method of treatment for couples in whom repeated failure of in-vitro fertilization is associated with the retrieval of dysmorphic oocytes in the presence of normal semen characteristics.
Cytoplasm↗
Risk factors for hepatic veno-occlusive disease following HLA-identical sibling bone marrow transplants for leukemia.
The objective was to analyze risk factors for veno-occlusive disease of the liver (VOD) after allogeneic bone marrow transplantation. A cohort of 1717 recipients of HLA-identical sibling transplants for leukemia between 1988 and 1990, in 200 transplant teams worldwide, was studied. Patients were scored as having VOD if liver tissue showed typical histologic features or if they had all three of the following: (1) jaundice; (2) hepatomegaly and right upper quadrant abdominal pain; and (3) ascites and/or unexplained weight gain. Patients surviving more than 7 days post-transplant without histologic or any of these clinical features of VOD were classified as not having VOD. Patient-, disease- and transplant-related characteristics of 95 patients with VOD were compared to those of 1514 without VOD. Variables correlated with an increased risk of VOD were: pretransplant conditioning with busulfan and cyclophosphamide compared to total body radiation (relative risk (RR) 2.8; P < 0.0001), pretransplant fungal infection (RR 4.1; P = 0.011), pretransplant Karnofsky performance score < 90% (RR 1.9; P = 0.012), prior liver disease (RR 1.9; P = 0.05) and age > 20 years (RR 1.8; P = 0.05). In patients receiving radiation for conditioning, intravenous immune globulin decreased VOD risk (RR 0.26; P = 0.003). This analysis identifies risk factors for VOD. The data suggest several strategies for modifying transplant regimens to reduce VOD risk and which patients might be suitable subjects for trials of strategies of VOD prevention.
Acute Disease↗
Taurocholate-stimulated leukotriene C4 biosynthesis and leukotriene C4-stimulated choleresis in isolated rat liver.
BACKGROUND/AIMS: Cysteinyl-containing leukotrienes seem to exert a cholestatic effect. However, leukotriene inhibitors were found to reduce bile salt efflux in isolated rat hepatocytes, suggesting a role for leukotrienes in bile flow formation. METHODS: In the isolated rat liver, the effects of two different concentrations of leukotriene C4 on bile flow and bile salt excretion are analyzed, as well as the possible effect of taurocholate on the hepatic production of cysteinyl-containing leukotrienes. RESULTS: Leukotriene C4 (0.25 fmol) increased bile salt excretion (+22.2%; P < 0.05), whereas a much higher dose (0.25 x 10(6) fmol) showed the known cholestatic effect, reducing bile salt excretion (-25.9%; P < 0.01). These dose-dependent biphasic effects were specific because they could be prevented by the simultaneous administration of cysteinyl-containing leukotriene antagonists. On the other hand, taurocholate administration induced a dose-dependent increase in biliary excretion of cysteinyl-containing leukotrienes. Furthermore, taurocholate increased messenger RNA levels of 5-lipoxygenase, a key enzyme in leukotriene biosynthesis. Taurocholate increase of hepatocyte intracellular calcium was not significant, suggesting that taurocholate effects are not mediated by stimulation of calcium metabolism. CONCLUSIONS: These results constitute evidence for the existence of a positive feedback mechanism by which bile salts stimulate the synthesis of leukotrienes that, in turn, stimulate bile salt excretion.
Animals↗
Vaccination of sheep against Schistosoma japonicum with either glutathione S-transferase, keyhole limpet haemocyanin or the freeze/thaw schistosomula/BCG vaccine.
The protective potential of glutathione S-transferase (GST), keyhole limpet haemocyanin (KLH) and the freeze/thaw (F/T) schistosomula/BCG vaccine was evaluated against Schistosoma japonicum in the natural sheep host. Groups of ten sheep each were vaccinated as follows: Group I: 2 x F/T 30,000 schistosomula+BCG 3 x 10(8) organisms, with a 2 week interval between vaccinations (F/T 'Low'). Group II: 3 x F/T 20,000 schistosomula+BCG 3 x 10(8), with 4 week interval (F/T 'High'). Group III: 2 x GST 0.24 mg+FCA (Freund's complete adjuvant) with 2 week interval (GST 'Low'). Group IV: 3 x GST 0.24 mg+FCA, with 4 week interval (GST 'High'). Group V: 2 x KLH 1.0 mg in phosphate-buffered saline (PBS), with 2 week interval (KLH 'Low'). Group VI: 3 x KLH 1.0 mg in PBS, with 4 week interval (KLH 'High'). Group VII: control (not vaccinated). Specific antibody, detected by GST-enzyme-linked immunosorbent assay (ELISA) and KLH-ELISA on the day after the last vaccination and 1, 2 and 3 weeks post-challenge, was found in all GST- or KLH-vaccinated groups. The same was found in F/T schistosomula-vaccinated groups against crude adult worm antigen (AWA). In Western blotting all GST-vaccinated sera recognized 26 kDa and 28 kDa bands on the challenge day and at 3 and 11 weeks post-challenge. Mean faecal egg counts between Weeks 6 and 10 post-challenge were reduced in a statistically significant way at five time points in the four groups, i.e. 83.38% (P < 0.005) in Group II, 49.29% (P < 0.025) in Group III, 47.9% (P < 0.05) and 71.15% (P < 0.01) in Group IV, 52.0% (P < 0.025) and 66.38% (P < 0.025) in Group VI. On autopsy and perfusion 1 week after the last faecal count, adult worm reductions were obtained of 40.36% (P < 0.05) in Group I, 37.26% (P < 0.025) in Group II, 24.73% (not significant) in Group III, 35.93% (P < 0.025) in Group IV, 27.46% (P < 0.05) in Group V and 33.81% (P < 0.01) in Group VI. Mean tissue egg densities were also reduced significantly in Groups III, IV and VI, especially in Group IV vaccinated animals. Mean liver egg granuloma diameters of the vaccinated groups were found to be less than those of the controls but there was no statistical significance.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Human oocyte activation following intracytoplasmic injection: the role of the sperm cell.
The aim of this study was to investigate whether the human spermatozoon participates in the activation of human oocytes following intracytoplasmic sperm injection (ICSI) and if so, by what mechanism. In the first series of experiments, we randomized human oocytes which had remained unfertilized after in-vitro fertilization (IVF) or ICSI, for intracytoplasmic injection with live spermatozoa, spermatozoa presumed to be dead and no spermatozoa. Secondly, unfertilized human oocytes and freshly ovulated mouse oocytes were randomized for intracytoplasmic and sub-zonal injection with human sperm cytosolic fraction (CF) before and after heat treatment. We found that oocyte injection with initially motile spermatozoa induces human oocyte activation at a significantly higher rate than injection with dead spermatozoa (61 versus 0%; P < 0.001) or injection without a spermatozoon (61 versus 14%; P < 0.001). Intracytoplasmic injection of CF activated both human and mouse oocytes at the same rate as sperm injection of human oocytes (activation rates of 70 and 65% respectively). This effect was greatly reduced by heat treatment of the CF. From these experiments we conclude firstly that the human spermatozoon injected intracytoplasmically contributes to human oocyte activation and secondly that the spermatozoon releases into the oocyte a heat-sensitive, intracellularly active factor, which is not species-specific.
Cell Death↗
Intracytoplasmic injection of human spermatozoa into mouse oocytes: a useful model to investigate the oocyte-activating capacity and the karyotype of human spermatozoa.
When intracytoplasmic sperm injection (ICSI) is performed, it is important to know the capacity of sperm cells to activate the oocytes, although knowledge of their ability to fuse with the oocytes is not vital. Hamster oocytes are not suitable for this purpose because they are easily activated by the injection procedure Itself. We therefore investigated whether mouse oocytes could be used to assess the activation properties of human spermatozoa. Mouse oocytes were randomized for injection with initially motile spermatozoa, medium, heat-treated or salt-extracted spermatozoa, and the survival and activation rates were examined. About half of the mouse oocytes survived the intracytoplasmic injection of a human sperm cell. Unlike hamster oocytes, the rate of activation provoked by the injection procedure itself was acceptably low (20%), resembling in this respect the behaviour of human oocytes. Following the injection of initially motile human spermatozoa, all mouse oocytes were activated. The injection of heat-treated or salt-extracted human spermatozoa resulted in activation rates of 14 and 15% respectively, comparable with the results following sham ICSI. These data support the hypothesis of a sperm-associated oocyte activation factor. In most activated oocytes, the human sperm nucleus decondensed to form a male pronucleus. Cytogenetic analysis at the first metaphase revealed that human sperm chromosomes were able to undergo replication in a heterologous environment.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Induction of sensitivity to ganciclovir in human hepatocellular carcinoma cells by adenovirus-mediated gene transfer of herpes simplex virus thymidine kinase.
We have analyzed the ability of a recombinant replication-defective adenovirus to transfer the thymidine kinase gene of herpes simplex virus (HSV-tk) into hepatocellular carcinoma (HCC) cells to confer sensitivity to ganciclovir. Three HCC cell lines (Hep3B, PLC/PRF/5, and HepG2) were efficiently infected in vitro by a recombinant adenovirus carrying lacZ reporter gene (AdCMVlacZ). Expression of HSV-tk in HCC cells infected with a recombinant adenovirus carrying HSV-tk gene (AdCMVtk) induced sensitivity to ganciclovir in a dose-dependent manner. A bystander killing effect was observed when 90% of uninfected tumor cells were mixed with only 10% of AdCMVtk-infected cells. These data show that recombinant adenoviruses are efficient vectors for transduction of drug-sensitizing genes to HCC cells in vitro. We suggest that a gene therapy approach to hepatocellular carcinoma can be established using adenoviral transfer of HSV-tk to tumor cells and subsequent administration of ganciclovir.
Adenoviridae↗
Treatment of rheumatoid joint inflammation with intrasynovial triamcinolone hexacetonide.
OBJECTIVE: To determine the effectiveness of intrasynovial triamcinolone hexacetonide coupled with joint rest (3 weeks upper extremity; 6 weeks lower extremity) in the treatment of joint and tendon sheath inflammation in patients with seropositive rheumatoid arthritis (RA). METHODS: The medical records of 169 patients with seropositive RA treated by a single rheumatologist for at least one year between 1974 and 1992 were abstracted. RESULTS: Nine hundred fifty-six injections were given to 140 patients; approximately 75% of injected synovial structures remained in remission during a mean followup 7 years; 218 injections were given into previously treated structures. The injection rate was about 2 per patient in the first year, half of which were given at the time of the first visit. The rate then approximated 0.6 injections per patient-year for the next 15 years. Joints in the right upper extremity were injected significantly (p = 0.01) more frequently than those on the left. CONCLUSION: Intrasynovial triamcinolone hexacetonide followed by rest is a very useful adjunctive modality in the treatment of seropositive rheumatoid arthritis.
Anti-Inflammatory Agents↗
Combination drug therapy of seropositive rheumatoid arthritis.
OBJECTIVE: To determine the longterm morbidity and mortality in a cohort of 169 patients with seropositive rheumatoid arthritis (RA) treated by a single rheumatologist with remittive agents used in combination. The effectiveness of a regimen combining pulse oral methotrexate, azathioprine and an antimalarial drug (MAH) was examined in detail. METHODS: All outpatient visits by patients followed for at least one year and up to 18 years (mean 7 years) were abstracted. Remittive antirheumatic drugs were used in combination to achieve progressive improvement. Univariate and multivariate analyses of the differences between first and last visit results in 9 process or outcome variables were calculated for the entire cohort, for those patients receiving or not receiving MAH at last visit, and for those patients taking methotrexate but not in combination with both azathioprine and an antimalarial. The numbers of patients in remission (Lansbury articular index zero), and near remission (articular index < 6) were determined for each of these groups. A survival curve was calculated. RESULTS: The entire patient cohort showed improvement in every variable except hemoglobin at the time of the last visit (p < 0.0004). On multivariate analysis MAH patients were improved only in American Rheumatism Association functional class compared to the other groups (p < 0.0001). Remission and near remission rates overall were 43 and 61%; for MAH patients 45 and 69% (p = n.s.). Survival was no different from that of the general population. Herpes zoster (17 patients) and second attacks of varicella (2 patients) were the most striking side effects. Prednisone use was reduced from 34 to 19% of patients and the mean daily dose was lowered from 9.3 to 5.9 mg. CONCLUSION: Combination therapy with multiple antirheumatic agents successfully controlled joint inflammation in 167 of 169 patients with seropositive RA; complete remission was achieved in 43% of patients. Survival of this patient cohort did not differ from that of the general population.
Administration, Oral↗
Alzheimer's disease survey in Guangdong of China.
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Aged↗
Molecular and cytogenetic studies of an X;autosome translocation in a patient with premature ovarian failure and review of the literature.
We have identified a patient with premature ovarian failure (POF) and a balanced X;autosome translocation: 46,X,t(X;6)(q13.3 or q21;p12) using high-resolution cytogenetic analysis and FISH. BrdU analysis showed that her normal X was late-replicating and translocated X earlier-replicating which is typical of balanced X;autosome rearrangements. Molecular studies were done to characterize the breakpoint on Xq and to determine the parental origin. PCR probes of tetranucleotide and dinucleotide repeat polymorphisms, and genomic probes were used to study DNA from the patient, her chromosomally normal parents and brother, and somatic cell hybrids containing each translocation chromosome. The translocation is paternally derived and is localized to Xq13.3-proximal Xq21.1, between PGK1 and DXS447 loci, a distance of 0.1 centimorgans. A "critical region" for normal ovarian function has been proposed for Xq13-q26 [Sarto et al., Am J Hum Genet 25:262-270, 1973; Phelan et al., Am J Obstet Gynecol 129:607-613, 1977; Summitt et al., BD:OAS XIV(6C):219-247, 1978] based on cytogenetic and clinical studies of patients with X;autosome translocations. Few cases have had molecular characterization of the breakpoints to further define the region. While translocations in the region may lead to ovarian dysfunction by disrupting normal meiosis or by a position effect, two recent reports of patients with premature ovarian failure and Xq deletions suggest that there is a gene (POF1) localized to Xq21.3-q27 [Krauss et al., N Engl J Med 317:125-131, 1987; Davies et al., Cytogenet Cell Genet 58:853-966, 1991] or within Xq26.1-q27 [Tharapel et al., Am J Hum Genet 52:463-471, 1993] responsible for POF.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Cardiovascular and pulmonary responses to Pichinde virus infection in strain 13 guinea pigs.
In fatal human Lassa fever, severe hypotension, circulatory shock, and pulmonary edema develop as terminal events. We examined cardiovascular and respiratory functions in strain 13 guinea pigs infected with Pichinde virus, an animal model for studying human Lassa fever. Cardiovascular functions were studied in anesthetized and conscious guinea pigs, whereas pulmonary functions were measured only on animals under anesthesia. In anesthetized animals, cardiovascular disturbances were severe and progressive from postinoculation day (PID) 10. Cardiac output, measured by thermodilution, decreased 28 to 53% below baseline values from PID 10 to 12 and was accompanied by a gradual reduction of mean arterial blood pressure and heart rate. Although left ventricular systolic pressure decreased significantly, the left ventricular +dp/dtmax and -dp/dtmax decreased only slightly on PID 12. Similar depressed cardiovascular responses were observed in conscious animals infected with Pichinde virus. Changes included decreased cardiac output, heart rate, cardiac work, cardiac power, and stroke volume, as well as increased total peripheral resistance and prolonged mean transit time. We postulate that a global cardiovascular dysfunction with the involvement of right and left sides of the heart may be the main cause of irreversible circulatory deterioration and death during Pichinde virus infection in strain 13 guinea pigs.
Animals↗
Epibatidine is a nicotinic analgesic.
Epibatidine, an alkaloid isolated from skin of the poison frog, Epipedobates tricolor, has been shown to be a very potent analgesic with a non-opioid mechanism of action. We found that epibatidine was about 120 times more potent and has longer duration than nicotine in analgesia, which could be antagonized by pretreatment with mecamylamine. Furthermore, epibatidine competed with high affinity (IC50 = 70 pM, Ki = 43 pM) for [3H]cytisine binding in rat brain preparations. These results indicated that the analgesic activity of epibatidine is attributed to its unique property as the most potent nicotinic acetylcholine receptor agonist.
Alkaloids↗