Homoplasmic 3316G-->A in the ND1 gene of the mitochondrial genome: a pathogenic mutation or a neutral polymorphism?
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Biomedical subjects
Publications and source records attributed to T Yang.
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A common anesthetic technique utilized during cardiopulmonary bypass (CPB) includes the use of various inhalation agents, such as isoflurane. The purpose of this study was to evaluate the effects of this agent on oxygen transfer during CPB. An in vitro model was designed using bovine blood. Blood flow was held constant at 2 l/min, while gas flow was manipulated at 1 and 3 l/min. The percentage of inspired oxygen (FiO2) was set at 50 and 100%, and isoflurane was manipulated to 1.0, 3.0 and 5.0%. Blood gas analysis, oxygen transfer, and inlet and outlet isoflurane concentrations were measured at each of the given conditions. A total of 12 trials with four oxygenators were conducted. In the four oxygenators used in our study, no significant differences in oxygenator performance were found. At conditions of 1 I/min gas flow, 50% FiO2 and 1% isoflurane, there were no significant changes in O2 transfer between baseline and measurements taken during isoflurane administration (100.18 +/- 12.49 vs 102.35 +/- 10.99 ml O2/min, p=0.8031). At 3 I/min gas flow, 100% FiO2 and 5% isoflurane, no significant differences were found (142.35 +/- 10.76 vs 154.04 +/- 8.95 ml O2/min, p=0.1459). The only significant differences found for oxygen transfer were between 50 and 100% FiO2, all other conditions being set equal (102.35 +/- 10.99 vs 137.68 +/- 8.62 ml O2/min, p=0.0023). In conclusion, increasing concentrations of isoflurane up to 5% does not affect the efficiency of oxygen transfer in an in vitro circuit. Further studies are necessary to evaluate the effects in an in vivo setting.
The influence of isoflurane (Iso) on the synthesis and secretion of phosphatidylcholine (PC) of alveolar type II cells (AT II cells) injured by hydrogen peroxide (H2O2) was investigated. After primary culturing for 32 h, AT II cells isolated and purified from adult Sprague-Dawley rats were randomly divided into six groups: control group, 02.8 mM Iso group, 2.8 mM Iso group, 75 microM H2O2 group, 75 microM H2O2 + 0.28 mM Iso group, and 75 microM H202 + 2.8 mM Iso group. Synthesis and secretion of phosphatidylcholine (PC) were detected by 3H-choline chloride incorporation. It was found that 0.28 mM and 2.8 mM Iso significantly reduced PC synthesis compared with the control group (p <0.05, p <0.01, respectively), but not PC secretion. 75 microM H2O2 markedly decreased the synthesis and secretion of PC in AT II cells compared with the control group (p <0.01). 0.28 mM and 2.8 mM Iso aggravated the decrease of PC synthesis induced by H2O2 (p <0.05, p <0.01, respectively), but did not affect PC secretion. These findings suggest that Iso itself may inhibit the synthesis of PC of AT II cells in vitro and further damage the cells' function under peroxidation.
OBJECT: Antagonists of the glycoprotein IIb/IIIa (GPIIb/IIIa) receptor complex are currently used for the treatment of acute coronary syndromes. The platelet GPIIb/IIIa mediates platelet aggregation, and blocking this receptor complex can reduce or prevent arterial thrombosis. To study the recanalization efficacy of a GPIIb/IIIa antagonist in treating cerebral ischemia, we investigated the therapeutic effects of murine 7E3 F(ab'), in a focal embolic cerebral ischemia model in rats. METHODS: Focal cerebral ischemia was produced by introducing an autologous thrombus into the right side of the middle cerebral artery (MCA). Thirty male Wistar rats were randomly divided into three groups of 10 rats each: control, 7E3 F(ab')2 administered 1 hour postischemia, and 7E3 F(ab')2 administered 3 hours postischemia. Animals in the therapeutic groups received intravenous infusion of 6 mg/kg 7E3 F(ab')2 at 1 or 3 hours following cerebral embolization. Brain infarct volume, neurobehavioral scores, duration of bleeding, and findings on angiograms of the MCA (before and after infusion) were assessed in all animals. Angiographic evaluation revealed full MCA recanalization in three of 10 animals in each 7E3 F(ab')2 treatment group. Animals in these groups exhibited a significant reduction in infarct volume when compared with animals in the control group: 1) infarct volume 1 hour postischemia, 22 +/- 13.9% (p = 0.005); 2) infarct volume 3 hours postischemia, 22.1 +/- 14.8% (p = 0.008); and 3) infarct volume in control animals, 42.4 +/- 16%. Postischemia treatment with 7E3 F(ab')2 also improved the animal's neurobehavioral performance. The duration of bleeding significantly increased by more than two times, but there was no associated increase in intracerebral hemorrhage in any group. CONCLUSIONS: On the basis of their findings, the authors conclude that murine 7E3 F(ab'), is a potent and safe antiplatelet agent in this experimental focal embolic cerebral ischemia model. Neuronal lesions were significantly reduced when the treatment was delayed up to 3 hours.
Quinolones are clinically important antibiotic drugs. One quinolone antibiotic, sparfloxacin (SPX), has been recently reported to increase the QT interval, and another quinolone, grepafloxacin (GRX), was withdrawn because it induced torsade de pointes (TdP), a polymorphic ventricular tachycardia (VT) linked to excessive QT interval prolongation. To determine whether SPX, GRX, and other recently developed quinolones, gatifloxacin (GAT) and moxifloxacin (MOX), have similar, potentially deleterious, properties we compared these agents in two ways. First, we measured their relative antagonist potency against the rapid component of the delayed rectifier K(+) current (I(Kr)), and second we determined the QT interval prolongation and inducibility of VT and TdP using a well established in vivo rabbit arrhythmia model. All of these agents are I(Kr) antagonists with the following IC(50) values (mean +/- S.E.) for I(Kr) block: SPX, 0.23 +/- 0.07 microM; MOX, 0.75 +/- 0.31 microM; GAT, 26.5 +/- 13.4 microM; and GRX, 27.2 +/- 11.6 microM. All agents also increased the maximum QT interval (mean +/- S.E.) from baseline (241 +/- 10 ms): SPX, 370 +/- 30 ms; MOX, 270 +/- 30 ms; GRX, 280 +/- 25 ms; and GAT, 255 +/- 23 ms. No agents caused TdP during a standard 30-min observation period, but SPX-treated animals developed nonsustained VT (three of six) and TdP (one of six) during an extended 60-min observation period. These findings show that I(Kr) block may be a common feature of many quinolone antibiotics, and that the proarrhythmic consequences vary according to I(Kr) antagonist potency, but are also influenced by additional, unidentified factors.
Ultrafiltration has been suggested as a means to reduce the morbidity associated with blood activation. However, the application of ultrafiltration to the highly activated blood of the cardiotomy suction subcircuit has not been investigated. The purpose of this study was to determine whether cardiotomy reservoir ultrafiltration (CRUF) would be effective in altering cytokine levels. Six swine, undergoing 90 min of cardiopulmonary bypass (CPB), were divided into two groups; one group was assigned to receive CRUF (N = 3), the other was to serve as controls and did not receive ultrafiltration (N = 3). Blood samples were analyzed for hematocrit, plasma-free hemoglobin, total protein, interleukin-8 (IL-8), and tumor necrosis factor alpha (TNF-alpha). Samples were taken pre-bypass, postheparinization, every 30 min during CPB, post-CPB and postprotamine. All data were analyzed using a one-way analysis of variance (ANOVA), with significance accepted at p < .05. There were no significant differences found between treatment and control groups for plasma-free hemoglobin levels (22.4 +/- 22.2 vs. 14.6 +/- 14.4; 40.1 +/- 26.1 vs. 40.0 +/- 19.3). After 90 min of ultrafiltration, there was a significant decrease in TNF-alpha (261.6 +/- 119.6 vs. 71.8 +/- 11.4; p = .02). Although IL-8 levels decreased from throughout the experiment, concentrations did not reach statistical significance. In conclusion, CRUF can be used without increasing cellular destruction, and can decrease certain cytokine levels. Our results suggest that further clinical studies should be undertaken utilizing this technique with a larger sample size.
Intraoperative autotransfusion is used in a variety of surgical procedures with the quantity of blood loss dependent upon numerous factors. These procedures may or may not produce a full autotransfusion bowl. The inadequate removal of contaminants has been correlated to the incomplete filling of bowls, resulting in a condition called "Salvaged Blood Syndrome." The purpose of this study was to assess the quality of aspirated whole blood after processing with an autotransfusion system using various fill volumes and two wash volumes. An in vitro circuit was designed to mimic the mechanical effects of extracorporeal flow on blood. Twenty-four Baylor-style bowls were filled at 400 mL min(-1) and washed at 300 mL min(-1). Two wash volumes, 1000 and 2000 mL, and three bowl volumes: low, mid, and full, were used in this study. The bowl volumes were determined by using red cell quantities of 60, 100, and 135 mL for the low-fill, mid-fill, and full bowls, respectively. Samples were drawn pre-autotransfusion and post-autotransfusion and analyzed for plasma-free hemoglobin, IL-8, white blood cell count, platelet count, albumin, and total protein. All data were analyzed using one-way analysis of variance (ANOVA) with significance accepted at p > or = .05. Plasma-free hemoglobin levels and hematocrit were concentrated significantly (p < .05) as bowl volume increased. A significant difference in IL-8 levels was found in the wash volumes in the low-fill bowls (p < .02). Platelet count was significantly decreased between the full bowl with 1000 mL wash and the full bowl with 2000 mL wash (p < .0004). Total protein reduction was significantly less in the low-fill bowl with 1000 mL wash as compared to the other bowl treatments (p < .05). In conclusion, the quality of the washed product did not vary significantly between fill or wash volumes, with the exception of the low-fill bowl with 1000 mL wash.
With surrogate tolerogenesis. the recipient immune system is engrafted within the donor pig before organ transplant. Chimeric pig hearts may resist hyperacute rejection by inducing accommodation. This hypothesis was tested using an ex vivo isolated piglet heart perfusion model. Processed sheep marrow was infused into fetal pigs at 45 days gestation. Heart explants from chimeric or nonchimeric pigs were suspended in a Langendorff apparatus and perfused with plasma from unsensitized sheep or sensitized sheep. Nonchimeric hearts perfused with plasma from unsensitized functioned for 240 min (N = 3). Nonchimeric hearts perfused with sensitized plasma deteriorated rapidly, functioning at 19+/-12 min (N = 6); Immunohistochemistry of heart graft revealed extensive deposition of IgG, IgM in the microvascular. In contrast, chimeric hearts perfused with sensitized plasma functioned for 183+/-46 min (N = 3)(p <.001); Deposition of IgG, IgM had substantially less. Heart grafts procured from chimeric pigs survived in the presence of antidonor IgG, IgM, and complement, demonstrating that chimeric pig hearts resist hyperacute rejection.
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OBJECTIVE: To construct a subtracted cDNA library of differentially expressed genes in human normal liver tissue and primary hepatocellular carcinoma (HCC) tissue. METHODS: Using the suppression subtractive hybridization (SSH), a novel technique has been described recently. cDNA fragments of missing or low expressing tumor suppressor genes in HCC tissue were isolated using paracancerous normal liver tissue and HCC tissue as targets. Then these cDNA fragments were directly inserted into T/A cloning vector to set up the subtractive library. Amplification of the library was carried out with transformation of E.coli by high voltage electroperforation. One hundred positive bacteria clones were randomly picked and identified using enzyme restriction method. RESULTS: The amplified library contained more than 4,000 positive bacteria clones. Random analysis of 100 clones with enzyme restriction method showed that all clones contained 200-600 bp inserts. CONCLUSIONS: A subtracted cDNA library of differentially expressed genes in human normal liver tissue and HCC tissue is constructed successfully with SSH and T/A cloning techniques. The library is efficient and lays solid foundation for screening and cloning new and specific missing or low expressing tumor suppressor genes of HCC.
OBJECTIVE: To understand the results of antibiotics use in curing neonatal pneumonia and to evaluate the time-effect of different drugs. METHODS: Through stratified sampling, all the hospitalized cases of neonatal pneumonia from 5 hospitals with different levels in Hunan province in five years were retrospectively studied. Analysis of time-effect for different antibiotics was done through Kaplan-Meier. RESULTS: Twenty-six kinds of anti-bacterium drugs were used in 685 cases of neonatal pneumonia, among which penicillin and ampicillin were mostly used but cephalosporins also became one of the main drugs used in treating neonatal pneumonia. Most cases were discovered (51.1%) using two kinds of antibiotics during the course of diseases through time-effect analysis. We found the effect of penicillin was better than others in treating neonatal pneumonia when used as basic medicine. It was not desirable to use two or more medicines at the beginning of the treatment. CONCLUSION: Penicillin and ampicillin were still the main drugs used in treating neonatal pneumonia but more cephalosporins were used than ever. The blindness in applying antibiotics should be recovered. From Kaplan-Meier analysis, we could better understand and evaluate the time-effects of different drug treatments.
OBJECTIVE: To demonstrate that a characteristic SYT-SSX fusion gene resulting from chromosomal translocation t (X; 18) (p11; q11) was detectable in archival paraffin-embedded synovial sarcoma tissues. METHODS: SYT-SSX fusion transcripts in 20 synovial sarcomas (histologic subtypes, 15 monophasic and 5 biphasic) were detected and analyzed by the reverse-transcriptase polymerase chain reaction and compared with the results from relevant pathological data. RESULTS: A specific SYT-SSX RT-PCR product was found in 19 of 20 (95%) synovial sarcomas tested and of the 13 tumors containing SYT-SSX2, 10 were monophasic. CONCLUSION: SYT-SSX fusion transcripts are considered as a defining diagnostic marker of synovial sarcomas and the subtypes of SYT-SSX fusion transcripts (SYT-SSX1 and SYT-SSX2) may yield prognostic information.
OBJECTIVE: A report of a group of patients with pancytopenia which might be related to abnormal immunity. METHODS: The clinical and laboratory features of 29 patients with positive bone marrow mononuclear cell (BMMNC) Coombs tests were analyzed. RESULTS: Most of these cases were pancytopenia with normal or decreased bone marrow cellularities and increased normoblasts. They were all found to have negative results of conventional hemolysis tests and hematopoietic nutrient determination and had no evidence of malignant clonal hematopoiesis. However, all of them showed positive BMMNC-Coombs test and good response to corticosteroids. CONCLUSION: Immunorelated pancytopenia might be caused by abnormal immunity (especially autoantibody) mediated destruction or abnormal function of blood cells. It is beneficial to differentiate immunorelated pancytopenia from aplastic anemia or myelodysplastic syndromes.
OBJECTIVE: To explore more effective regimen for reducing early mortality of severe aplastic anemia (SAA) and improving therapeutic effectiveness. METHODS: Antilymphocyte globulin/antithymocyte globulin (ALG/ATG) and cyclosporine A (CsA) (sequential intensified immunosuppressive therapy, SIIST), with or without hematopoietic growth factors (HGFs) were administered to 73 SAA patients in a prospective randomized clinical trial to test the effectiveness of the addition of HGFs for the patients. RESULTS: The response rate of SIIST with HGFs group was significantly higher than that of SIIST alone group (89.2% vs 63.9%), with lower rates of early infection (24.3% vs 55.3%) and mortality (4.0% vs 16.7%), shorter duration of cytopenia and blood transfusion dependence and faster recovery of bone marrow hematopoiesis. The addition of HGFs to SIIST was tolerated well in all patients. There was no difference in the treatment outcome of the two groups with GM-CSF plus Epo or G-CSF plus Epo. CONCLUSION: The use of HGFs in combination with SIIST could reduce early infection and mortality rates and, therefore, improve the response rates in SAA patients.
OBJECTIVE: To study the patterns of transformation from myelodysplastic syndromes (MDS) into acute leukemias (AL). METHODS: Leukemic transformation of MDS patients was dynamically followed up and the clinical manifestations, peripheral blood and bone marrow pictures, karyotypes, immunophenotypes, response to treatment and prognosis of post MDS acute leukemia (postMDS-AL) were observed. RESULTS: During the past eight year and seven months, 21 (13.91%) of 151 MDS patients progressed to overt leukemia with a median interval of 5 (1 - 21) months. There were no significant differences among the rates of leukemia from RA, RAEB and RAEB-t groups. The transformation was developed either gradually or rapidly. There were five parameters related to the leukemic transformation: under 40 years of age, pancytopenia, more than 0.15 blasts in bone marrow, at least two types of abnormal karyotype and combined chemotherapy. All of the 21 post MDS-AL were acute myeloid leukemia (AML); and most of them were M(2), M(4) and M(5). Two (9.52%) post MDS-AML developed extramedullary infiltration. Leukopenia was found in 47.62% of patients. Two third of the patients, whose bone marrows were generally hypercellular, showed neutropenias. After evolving into AML, 8 (47.06%) patients developed abnormal karyotypes. High expression of immature myeloid antigens, including CD(33) (49.83 +/- 24.50)%, CD(13) (36.38 +/- 33.84)%, monocytic antigen CD(14) (38.50 +/- 24.60)%, and stem cell marker CD(34) (34.67 +/- 30.59)% were found on bone marrow mononuclear cells of post MDS-AML cases. In some cases, lymphoid antigens, such as CD(5), CD(7), CD(9) and CD(19) were coexisted with myeloid antigens. A low complete remission rate (31.25%) and short survival duration with median survival of 6 (1 - 28) months were found in patients with post MDS-AML treated by induction therapy. CONCLUSION: MDS was at high risk of evolving into AML, either gradually or rapidly. Patients with post MDS-AML had specific biologic features and worse prognoses.
OBJECTIVE: To evaluate the ultrasonic measurements of parturient fetal cerebellar diameter (CD), liver length(LL), kidney length (KL) and femur thigh soft tissue thickness(FSTT) for the estimation of fetal weight. METHODS: Ultrasonic measurements of the parturient fetal cerebellar diameter, liver length, kidney length and femur thigh soft tissue thickness were made in 115 cases. The data on these parameters were analyzed with statistical methods, and a multiple linear regressional equation for predicting the fetal body weight was derived. The calculated value of fetal body weight and the estimated parameters of the fetal body were compared with the actually measured values immediately after birth. The error of estimation was analyzed. RESULTS: CD, LL, KL and FSTT were significantly correlated with neonatal birth weight, the coefficient of multiple correlation R = 0.9425 (P < 0.001); among the 115 cases, 101 had absolute error less than +/- 200 g, with an agreement rate of 88%. The sensitivity and accuracy for detection of normal fetus were 98.13% and 94.78% respectively. The multiple linear regression equation derived was BW = -1009.914 + 356.1303FSTT + 354.0682KL + 236.8484 LL + 179.7384 CD. CONCLUSION: The equation is a simple, accurate and valuable equation for the estimation of fetal weight and can be used in clinical practice.
OBJECTIVE: This study was aimed to investigate the bonding effect of laser welding on ceramic fused to metal. METHODS: Ten laser welded CW-PA ceramo-alloy rods were fused with porcelain at fusion zone. The porcelain-metal bond strength was measured with pull-through test. SEM examination and EDAX analysis were performed. Ten non-welded CW-PA ceramo-alloy pull-rod plates were used as comparison. RESULTS: The results showed that the bond strength of laser welded sample was 41.32 +/- 6.69 MPa, approaching to 45.71 +/- 9.98 MPa of the non-welded sample (P > 0.05). The microscope displayed the interface compacted union of the two phase boundary. There was no change in the elements and their ratio at the fusion zone. CONCLUSION: These results indicate that laser welding does not affect ceramic fused to metal.
OBJECTIVE: To explore the regulating roles of tissue-type plasminogen activator (tPA) in the differentiation of keratinocyte in the human epidermis. METHODS: Immunocytochemistry and in situ hybridization were employed to study tPA expression quantitatively and qualitatively in early, middle and late human embryos skin respectively. RESULTS: (1) The expression of tPA was significantly increased in the development of embryonic period, with the highest level in the middle embryonic phase, but the transcription of tPA still kept rather high level in the late human embryonic phase. (2) tPA was mainly localized in the superficial, more differentiated layers of the epidermis. (3) tPA was localized in peripheral cytoplasm of keratinocyte. CONCLUSION: tPA participates the regulation of the keratinocyte differentiation.