Biomedical subjects
Publications and source records attributed to M Ma.
Graft-vs-host disease (GVHD) is a potentially treatable cause of progressive neurologic decline after bone marrow transplantation (BMT). The authors present histologic confirmation of CNS granulomatous angiitis in a child with chronic GVHD after BMT. Since cranial MRI showed only nonspecific findings, CNS vasculitis associated with GVHD after BMT may be underdiagnosed.
To assess the contribution of the alternative pathway in complement activation and host defense and its possible role in the regulation of systemic energy balance in vivo, factor D-deficient mice were generated by gene targeting. The mutant mice have no apparent abnormality in development and their body weights are similar to those of factor D-sufficient littermates. Complement activation could not be initiated in the serum of deficient mice by the alternative pathway activators rabbit erythrocytes and zymosan. Surprisingly, injection of cobra venom factor (CVF) caused a profound and reproducible reduction in serum C3 levels, whereas, as expected, there was no C3 reduction in factor B-deficient mice treated similarly. Studies of C3 and factor B activation in vitro by CVF demonstrated that in factor D-deficient serum the alpha chain of C3 was cleaved gradually over a period of 60 min without detectable cleavage of factor B. CVF-dependent C3 cleavage in the deficient serum required the presence of Mg(2+), whereas in normal mouse serum the presence of divalent cations was not required. These results suggest that in mouse proteolytic cleavage of factor B by factor D is not an absolute requirement for the zymogen to active enzyme conformational transition of CVF-bound factor B. Kinetics of opsonization of Streptococcus pneumoniae by C3 fragments was much slower in factor D-deficient serum, suggesting a significant contribution of the alternative pathway to antibacterial host defense early after infection.
OBJECTIVE: To investigate if infection of human herpesvirus type 8 (HHV8) exists in Chinese patients with multiple myeloma (MM), and to identify the relationship between clinical manifestation and the viral load in bone marrow biopsy samples. METHODS: Real-time quantitative PCR was conducted to define the viral load of HHV8 in bone marrow biopsy samples from 23 patients with MM. Nested PCR was conducted to amplify the KS330(233)Bam fragment of HHV8 from peripheral blood mononuclear cells, bone marrow aspirates and bone marrow biopsy samples. RT-PCR was used to study the expression of suspected oncogenes: vIL-6 and vIRF-1 genes. Bone marrow biopsy samples of 5 patients with blood diseases other than MM and 5 patients with non-blood system diseases were used as controls. PCR product of BCBL-1 cell line was used as positive control. RESULTS: (1) The positive rate of HHV8 in bone marrow biopsy samples from patients with MM was 69.6% (16/23) by real-time fluorescence quantitative PCR, and 82.6% (19/23) by nested-PCR. 16 bone marrow samples positive by fluorescence quantitative were positive too by nested-PCR. However, 3 bone marrow samples positive by nested-PCR were negative by fluorescence quantative. HHV8 was positive in only one of the 25 bone marrow aspirates from patients with MM (4%) and in none of the 20 peripharal blood samples from patients with MM. PCR showed negative result in 7 bone marrow aspirates taken form 13 MM patients with positive result by fluorescence quantative PCR. HHV8 was negative in bone marrow biopsy samples from patients with other diseases. HHV8 was negative in the peripheral blood samples from 16 MM patients, among which 9 out of the 11 cases with bone marrow biopsy samples taken showed HHV8 positive by fluorescence quatative PCR. Bone marrow biopsy samples of all patients with other blood diseases and non-blood system diseases were HHV8 negative. RT-PCR showed that among 12 MM patients the expression rate of vIRF-1 was 83.3% (10/12), and expression rate of vIL-6 was 0. The PCR positive products tallied with the sequence of HHV8 DNA. Clinical analysis showed that all of the patients with negative results had had chemotherapy. CONCLUSION: There is a certain association between multiple myeloma pathogenesis and HHV8. In detection of HHVb, nested-PCR is more sensitive than fluorescence quantitaative PCR. The viral gene vILR-1 plays a certain role in the pathogenesis of MM.
We show that the recently proposed S = 2 bond model with orbital degrees of freedom for insulating V2O3 not only explains the anomalous magnetic ordering but also other mysteries of the magnetic phase transition. The model contains an additional orbital degree of freedom that exhibits a zero temperature quantum phase transition in the Ising universality class.
A computer-controlled electromagnetic spinal cord injury device (ESCID) has been adapted to develop a mouse model of spinal cord contusion injury. In the present study, we have extended this model in C57Bl/6 mice with behavioral and histopathological outcome assessment. Three groups of mice received a laminectomy at the T(9) vertebral level followed by a contusion injury from a predetermined starting load of 1500 dynes. Contusion was produced by rapid displacement of the spinal cord to a peak distance of 0.3, 0.5, or 0.8 mm, with the entire injury and retraction procedure completed over a 23-ms epoch. Control groups received laminectomy alone or complete transection. Functional recovery was examined for 9 weeks after injury using the BBB locomotor rating scale, grid walking, and footprint analysis. Distinct patterns of locomotor recovery were evident across the five groups. Measurements of spared white matter at the epicenter, lesion length, and cross-sectional area of fibronectin-immunopositive scar tissue were also significantly different between injury groups. The severity of injury corresponded with the biomechanical measures recorded at the time of impact as well as with behavioral and histological parameters. The results demonstrate that graded contusion injuries can be produced reliably in mice using the ESCID. The data provide a thorough and quantitative analysis of the effects of contusion injury on long-term behavioral and histological outcome measures in this strain and species.
Current contents of persistent organic contaminants, polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs) and the congeners (naphthalene, fluorene, phenanthrene, anthracene, fluoranthene, pyrene, chrysene, benzo(a)anthracene, benzo(a)pyrene and benzo(e)pyrene), DDTs and metabolites in the intertidal sediments of the Bohai Sea and the Yellow Sea were studied. The mean levels of DDTs, PAHs and PCBs were 177.52, 877.2 and 3.4 ng g-1 dry weight, respectively. The spatial trends of the contaminant residue levels were analysed too.
Semipermeable membrane devices containing a neutral lipid triolein (triolein-SPMD) and conventional dichloromethane extraction were used to monitor the presence and concentrations of priority organic pollutants in a sewage treatment process in Beijing, China. Both samples gave similar information on the presence of target PCB congeners, PAHs, Organochlorine pesticides and substituted benzenes in sewage at all sites. After 20 days' sampling, the concentrations of contaminants in triolein of SPMD were much higher than those in dichloromethane extracts, which resulted in easier analysis, improved the detection limits, and increased the accuracy. Previous field mean sampling rates for SPMD were used to estimate concentrations of PCB congeners in sewage, which compared to their determined concentrations by dichloromethane extraction. The consistency and superiority of SPMD technology were proved for the detection of priority organic contaminants from sewage. Lower removal rates for PCB congeners and PAHs coincided with the persistence of them in environment. More attention should be paid to urban sewage treatment process adopting activated-sludge method, where priority organic pollutants might not be removed, even present higher concentrations after treatment.
In order to investigate the frequency of HHV-8 in MM patients from another geographic location, we obtained fresh bone marrow (BM) biopsies from Turkish patients with MM (n = 21), monoclonal gammopathy of undetermined significance (MGUS) (n = 2), plasmacytoma (n = 1) with BM plasma cell infiltration, various hematological disorders (n = 6), and five healthy Turkish controls. The frequency of HHV-8 was analyzed by polymerase chain reaction (PCR) in two independent laboratories in the USA and in Turkey. Using fresh BM biopsies, 17/21 MM patients were positive for HHV-8 whereas all five healthy controls, and six patients with other hematological disorders were negative. Two patients with MGUS, and one patient with a solitary plasmacytoma were also negative. The data from the two laboratories were completely concordant. Also using primer pairs for v IRF and v IL-8R confirmed the results observed with the KS330233 primers. Furthermore, sequence analysis demonstrated a C3 strain pattern in the ORF26 region which was also found in MM patients from the US. Thus, HHV-8 is present in the majority of Turkish MM patients, and the absence of the virus in healthy controls further supports its role in the pathogenesis of MM.
We compared epidural (n = 17) and intravenous (n = 20) patient-controlled analgesia (PCA) using pethidine (bolus 10 mg, lockout interval 10 min, 4-h maximum dose 3 mg.kg(-1)) after total gastrectomy. We found that mean (SD) pethidine consumption in the first 24 h was 33% less in the epidural group [255 (85) mg] than in the intravenous group [379 (129) mg, p = 0.002], although most of this difference occurred in the first 8 h. Plasma concentrations of pethidine were lower at 8 h (p < 0.01) in the epidural group, but were similar at 24 h. Pain scores, side-effects, patient satisfaction and patient outcome were similar between groups. Epidural and intravenous pethidine PCA provided similar efficacy after major abdominal surgery, although the epidural route can reduce the amount of pethidine used initially.
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PURPOSE: The initial purpose of this study was to determine the effects of intravascular adenoviral vector-mediated gene transfer of endothelial nitric oxide synthase (AdeNOS) on experimental hindlimb ischemia in the rat. Unexpectedly, administration of AdeNOS immediately after induction of acute limb ischemia led to limb gangrene. We subsequently sought to define the molecular mechanisms responsible for this unusual effect and to devise adenoviral gene transfer strategies to prevent the development of gangrene in acutely ischemic limbs. METHODS: Phosphate-buffered saline or adenoviral vectors containing the bovine endothelial nitric oxide synthase gene (AdeNOS) or no transgene (Ad-E1) were injected intra-arterially into the hindlimb of a rat under vascular isolation immediately after surgical induction of severe ischemia. Hematoxylin and eosin staining was performed on muscle sections to evaluate inflammation. A separate group of animals was injected with an adenovirus containing a nontranscribable genome, treated with cyclosporine, or received delayed administration of the adenoviral vector. Gene expression after delayed adenoviral gene transfer was assessed with immunohistochemistry, Western blotting, and nitric oxide synthase (NOS) activity assay. RESULTS: Both AdeNOS and Ad-E1 caused gangrene of the entire hindlimb within 12 days in a dose-dependent manner, at a threshold concentration of 1 x 10(9) plaque-forming unit/mL. Adenoviral delivery was associated with more inflammation and edema compared with phosphate-buffered saline histologically. Inactivation of adenoviral DNA transcription did not affect induction of gangrene. However, gangrene was prevented by concurrent immunosuppression with cyclosporine or delayed administration of the vector. Delayed administration allowed adenoviral gene expression as determined by immunohistochemistry, NOS protein levels, and an assay of NOS enzyme activity. CONCLUSION: Intra-arterial administration of adenoviral vectors, under vascular isolation, immediately after induction of acute ischemia causes inflammation and subsequent limb gangrene. The inflammatory response is unrelated to the expression of the recombinant transgene or the adenoviral genome and is likely due to the adenoviral capsid proteins. However, administration of cyclosporine or delayed injection of the adenoviral vector is a method that can be used for adenoviral mediated gene transfer in limb ischemia.
Gastric cancers are commonly subdivided into intestinal and diffuse subtypes on a morphologic basis, supported by corollary evidence of differences at the pathogenetic and molecular levels. Chronic atrophic gastritis with intestinal metaplasia is a common precursor lesion for the intestinal type of carcinoma. To identify early molecular changes, in this study we have examined 13 surgical specimens both for the expression of E-cadherin, p53 and beta-catenin by immunohistochemistry and for methylation of the CDH1 promoter (E-cadherin) by bisulfite genomic sequencing of laser capture microdissected samples. Each specimen examined contained areas of normal (nonmetaplastic) gastric mucosa, as well as areas of intestinal metaplasia and/or carcinoma. Reduced or absent E-cadherin and partial to complete methylation of one to multiple CpG sites examined in the CDH1 promoter were observed in all of the metaplasia samples. Thus, the methylation status of the CDH1 promoter and expression of E-cadherin together provide strong evidence that loss of E-cadherin is an early event in intestinal type gastric carcinogenesis. In contrast, expression of p53, assumed to be mutant p53, was generally not detected (except for isolated cells) until the carcinoma stage in tissues from these patients. These results suggest that mutation of p53 is a late event in intestinal type gastric cancer. The level of beta-catenin expression did not appear to change between normal, metaplastic and carcinoma cells of intestinal type, and no nuclear staining was visible in any of the tissues. These results suggest that the Wnt signaling pathway is not upregulated in this type of cancer.
UNLABELLED: Cessation of IV patient-controlled analgesia (PCA) in the postoperative period is often an arbitrary clinical decision. We conducted a prospective survey of patients 24 h after cessation of IV PCA morphine to determine whether they wished to be restarted on PCA, and to evaluate factors affecting this decision. One hundred and fifteen patients were surveyed over a 3-mo period. Thirty-eight patients (33%) wished to restart PCA. The most common reason was the expectation that IV PCA would be more effective. Age, sex, type of surgery, duration of PCA use, side effects, pain scores, and reasons for cessation of PCA did not affect the decision. The reasons given by those who did not wish to restart PCA were minimal pain (51.9%), inconvenient PCA machine (15.6%), ineffective analgesia by IV PCA (11.7%), side effects during PCA (11.7%), and wishing to tolerate pain (7.8%). PCA morphine consumption in the 24-h period before cessation of PCA (mean [SD]) was larger in patients wishing to restart PCA than in those who did not (21.1 [14.8] mg vs 15.1 [15.1] mg; P < 0.05). In conclusion, the clinical decisions to cease IV PCA do not predict patient acceptance of and satisfaction with the decision and with subsequent pain treatment. Morphine consumption may predict a patient's acceptance of ceasing PCA. IMPLICATIONS: We surveyed patients 24 h after cessation of IV patient-controlled analgesia (PCA). This survey revealed that the usual clinical reasons to stop IV PCA might not be the most appropriate. Patients have different reasons why they wish to restart or not restart IV PCA. The cessation of PCA should be individualized.
OBJECTIVES: The goal of this study was to compare the cardiovascular responses to behavioural stressors of three groups of adolescents who differed in blood pressure status across assessments. DESIGN: Casual blood pressure of adolescents who were identified as having elevated blood pressure during a school screen was re-evaluated in the laboratory. The adolescents were classified into two groups: (i) those with consistently elevated blood pressure across school and laboratory assessments and (i) those with labile blood pressure whose blood pressure in the laboratory was below 130/80 mmHg. A comparison group of adolescents with consistently normal blood pressure was also included. METHODS: Cardiovascular parameters were assessed during rest and during two behavioural stressors, the evaluated speaking task and the mirror tracing task. RESULTS: Adolescents with elevated blood pressure were more vascularly responsive across stressors than adolescents with labile blood pressure, who, in turn, were more reactive than adolescents with normal blood pressure. CONCLUSIONS: These results suggest that vascular reactivity to behavioural stressors may be useful in predicting risk of hypertension because of its sensitivity in distinguishing adolescents with consistently elevated blood pressure from those with labile blood pressure and those with normal blood pressure.
The cardioprotective effects of quinapril, an angiotensin-converting enzyme inhibitor, were studied in a rat model of heart failure. Twenty-six rats were divided into two groups: one given 20 mg/kg/day quinapril (n = 11), and controls given 0.5% methylcellulose (n = 15). After oral administration for 1 month, quinapril reduced heart weight (from 1.28+/-0.05 to 0.87+/-0.02 g; p < 0.05) without changing body weight. Quinapril lowered left ventricular end-diastolic pressure (from 14.1+/-2.0 to 6.6+/-1.5 mmHg; p < 0.05) and central venous pressure (from 2.7+/-0.9 to 0.7+/-0.4 mmHg), and increased +/- dP/dt (from +2409+/-50 to +3569+/-169 mmHg/s, and from -2318+/-235 to -3960+/-203 mmHg/s; both p < 0.01). The area of myocardial fibrosis was markedly reduced by quinapril (6+/-3%) as compared with controls (29+/-6%; p < 0.01). Expression of transforming growth factor (TGF)-beta1 mRNA was markedly increased in controls as compared with age-matched normal rats. The increase in level of TGF-beta1 mRNA was significantly suppressed by quinapril (from 17.1+/-6.2 to 9.00+/-2.40; p < 0.05). These observations indicated that quinapril has cardioprotective effects on heart failure, and that the beneficial effects may be partly explained by attenuation of fibrotic response through suppression of TGF-beta1 mRNA expression.
The cardioprotective effects of bisoprolol were studied in a rat model of severe heart failure induced by autoimmune myocarditis. Twenty-eight days after immunization, Lewis rats were divided into four groups: 0.1 mg/kg/day bisoprolol (Group 0.1), 1.0 mg/kg/day bisoprolol (Group 1) and 10 mg/kg/day bisoprolol (Group 10), and vehicle (0.5% methylcellulose; Group V) (all groups, n = 13). After oral administration for 1 month, heart weight, mean blood pressure, heart rate, central venous pressure, peak left ventricular pressure, left ventricular end-diastolic pressure, +/- dP/dt, and area of fibrosis were measured. Although bisoprolol reduced heart rate (399+/-11/min in Group V, 382+/-10/min in Group 0.1, 348+/-8/min in Group 1 and 302+/-9/min in Group 10) and increased survival (62% in Group V, 69% in Group 0.1, and 100% in Group 1 and Group 10) in a dose-dependent manner, this drug did not change heart weight, the area of myocardial fibrosis or hemodynamic parameters. These observations suggested that bisoprolol may improve survival independently of its effect on left ventricular function by reducing sudden death in patients with severe heart failure.
This study was conducted to establish the large-capacity culture methd of cytokine-induced killer (CIK) cells for clinical therapy and assess its effect on the fuction of cell-mediated immunity following autologous CIK cells reinfusion. Autologus CIK cells were expanded in 1000 ml culture-bag and reinfused back. The MTT method was used to test the cytotoxic activity of CIK cells before and after reinfusion. The results showed that the total amount of autologous CIK cells reinfusion exceeded 1.6 x 10(10) with the use of the culture method of large-capacity. The PBMNC from patients treated by CIK cells showed significant increase in cytotoxic activity, no side effects were observed, and therefore the large-capacity culture method of CIK cells is a simle and safe therapy for treating the minimum residue of diseases.
Saucernetilignan-8 (Sc-8), which was isolated from Saururus chinesis, has significant anti-inflammatory effect.