Volume 112  ·   Issue 12  ·  1999

OBJECTIVE To evaluate the significance of serum antineutrophil cytoplasmic antibodies (ANCAs) and the effects of immune suppressive treatments on its activity in patients with pauci-immune crescentic glomerulonephritis (PICGN). METHODS Serum ANCAs and myeloperoxidase (MPO)-ANCA were detected by indirect immunofluorescence and enzyme-linked immunosorbent assay (ELISA) methods respectively, and the renal tissues infiltrating cells including CD4+, CD8+, CD68+ and PCNA+ cells were determined by four-layer peroxidase-antiperoxidase (PAP) method. The clinical manifestations, pathologic features and immune pathologic changes in patients with positive ANCAs were compared with that in patients with negative ANCAs. The effects of immune suppressive therapy on clinic and pathologic changes as well as ANCAs activity were also investigated in ANCAs positive and ANCAs negative patients. RESULTS Both of clinic active manifestations such as the degree of hematuria, rapidly progressive renal failure and pathologic active features including segmental capillary necrosis and vasculitis were much common in patients with positive ANCAs as compared with that in patients with negative ANCAs. The number of infiltrating cells in renal tissue, especially CD4+ cells, was markedly higher in ANCAs positive patients than that in ANCAs negative patients. The effects of immune suppressive therapy were also much better in patients with positive ANCAs than that in patients with negative ANCAs. CONCLUSIONS Serum ANCAs is not only a marker for diagnosis of systemic vasculitis, but also a sensitive predictor for evaluation of diseases' activity and treatment in patients with PICGN. The good effect of immune suppressive treatments on patients with PICGN is partially associated with the degree of ANCAs activity.

OBJECTIVE To investigate the effects of various concentrations of sevoflurane and propofol and a combination of the two agents on chloride current induced by bath utilization of 3×10-6 mol/L gamma-aminobutyric acid (GABA) in the rat dorsal root ganglia neurons maintained in primary culture. METHODS Sensory neurons from rat dorsal root ganglia were dissociated and cultured. The whole-cell patch clamp technique was used to record chloride current. All drugs were applied with a rapid perfusion system, named "Y-tube" method. RESULTS The peak chloride current amplitude was induced by 3×10-6 mol/L GABA with substantially increasing of both sevoflurane and propofol. Additionally, desensitization of IGABA induced by either propofol or sevoflurane was not observed. We examined actions of various concentrations of propofol (3×10(-7), 1×10-6, 3×10-6 mol/L), sevoflurane (7×10(-4) mol/L) and their combination at concentrations relevant to clinical anesthesia on IGABA propofol (3×10(-7), 1×10-6, 3×10-6 mol/L) produced a concentration-dependent increase in the response to 3×10-6 mol/L GABA on IGABA. When combined with 7×10(-4) mol/L sevoflurane, the potentiation of response to GABA obtained with various concentrations of propofol was not different from a theoretical additive response (P>0.05). CONCLUSIONS Either sevoflurane or propofol and their combination at clinically relevant concentrations potentiate the GABA-induced chloride current, which may at least partially contribute to the anesthetic mechanism. Additive interaction obtained with a co-application of propofol and sevoflurane may provide an evidence for a clinical combination of these two anesthetic agents.

OBJECTIVE To examine the expression of heat shock protein (HSP) 90β in human gastric cancer tissue and SGC7901/VCR of MDR-type gastric cancer cell line. METHODS Immunohistochemical staining and in situ hybridization methods. RESULTS Heat shock protein 90β was mainly located in the cell cytoplasma and weakly expressed in non-cancerous gastric mucosa. The expression rates of HSP90β in normal gastric mucosa, gastritis and paracancer tissues were 11.76%, 13.04% and 11.42% respectively, and there were no significant differences between them (P>0.05). The expression of HSP90β was increased in gastric cancer. The positive rate of HSP90β in gastric cancer tissue was 30.00%, and was higher than non-cancerous gastric mucosa (P<0.05). The expression rates of HSP90β in well differentiated, moderately differentiated, poorly differentiated gastric cancer and mucinous carcinoma were 15.38%, 31.25%, 33.33%, and 42.85% respectively. The expression of HSP90β in SGC7901/VCR of MDR-type gastric cell line was higher than in its parental cell line SGC7901. In situ hybridization showed that the positive signal of HSP90β was mainly located in the cell cytoplasma. CONCLUSIONS The expression of HSP90β was higher in gastric cancer tissue than in non-cancerous gastric mucosa. In gastric cancer tissue, the expression of HSP90β was greater in poorly differentiated cancer tissue, and in SGC7901/VCR of MDR-type gastric cancer cell line the expression of HSP90β was higher than that in its parental cell line SGC7901.

OBJECTIVE To determine the length of protection by murine immunization with living third-stage hookworm larvae (L3) as measured by reduction in worm burden and host serologic antibody responses. METHODS Outbred male (Kunming strain) mice were immunized subcutaneously with 500 L3 once every 2 weeks for a total of immunization for 3 times, and then challenged orally with 1000 L3 for 1 to 8 weeks after the final immunization. Host protective immunity was determined both by the reduction in worm burden as measured by the number of L3 recovered from murine lungs 48-hour post-challenge, as well as by measurement of circulating antibodies. Histopathological responses were also examined. Non-immunized mice served as negative controls. RESULTS The protection by L3 immunization declined over time. One or 2 weeks after the final immunization, worm burdens were reduced 72% and 77.5% after challenge respectively. In contrast, only 37% reduction in worm burden was observed when the L3 challenge was delayed by 4 weeks and protection was almost entirely lost when there was an 8 week delay between the time of final immunization and challenge. The reduced level of protection over time partially correlated with diminishing L3-specific antibody responses. Host inflammation in the lungs of immunized mice also diminished. CONCLUSIONS The protection afforded by living L3 immunization is maximal for the first two weeks after immunization, but then declines significantly over the ensuing weeks.

OBJECTIVE To establish noninvasive semiquantitative ultrasonic criteria for evaluating liver fibrosis and differentiating cirrhosis from chronic hepatitis. METHODS A total of 66 HBsAg positive patients (chronic hepatitis 42 patients, cirrhosis 24) were included. Ultrasonography was performed 24 hours before liver biopsy. A fibrotic scoring system was used to evaluate the ultrasound findings in contrast with fibrotic stages in each patient. RESULTS The total liver fibrotic scores had a significantly positive correlation with the histological liver fibrotic stage (r = 0.952, P &lt; 0.001); the stage of histological liver fibrosis (Y) was calculated by the total fibrotic scores (X) according to the experiential formula: Y = X/2 -2; receiver operating curves (ROC) showed that the best cut-off values for differentiating cirrhosis from chronic hepatitis was 10 with a sensitivity of 87.8% and a specificity of 97.6%. CONCLUSIONS The total fibrotic scores of ultrasonic dimensional image provide a semiquantitative marker to evaluate liver fibrosis and differentiate cirrhosis from chronic hepatitis.

OBJECTIVE To determine if changes in superoxide dismutase (SOD) in the brain occur in the hypertensive state. METHODS We compared the levels of the two main subtypes of this enzyme in spontaneously hypertensive rats (SHR) with age-matched normotensive Wistar Kyoto (WKY) rats using enzyme activity estimation, Western blotting for enzyme contents, and Northern blotting of mRNA level. Five discrete brain regions, cerebrocortex, hypothalamus, hippocampus, the remaining non-cortex cerebrum (NCC area), and cerebellum, were employed for comparison in 30-31 weeks old rats. RESULTS A lower level of both Mn-SOD activity and Mn-SOD mRNA expression was found in all areas of the brain of SHR as compared with WKY rats. Also, the mRNA levels of Cu, Zn-SOD in the brain of SHR differed from WKY rats in parallel to the enzyme activities. The activity and mRNA expression of Cu, Zn-SOD were lower in the hypothalamus and cerebellum of SHR but the mRNA level and the activity in hippocampus were significantly higher in the SHR compared to WKY rats. No differences for Cu, Zn-SOD were observed in cerebrocortex or NCC area in the two species. However, the amount of SOD enzyme subtypes, determined by Western blotting analysis, was not different between SHR and WKY rats. CONCLUSIONS The RESULTS indicate a lower gene expression and less activity of Mn-SOD in SHR brain. This alternation of SOD may be one of the important factors for the vulnerability of the brain from oxygen free radicals or may be related to the pathogenesis of hypertension in this species.

OBJECTIVE To investigate expression of Evi-1 and MDS1-Evi-1 genes in myelodysplastic syndromes (MDS) and post-MDS acute myeloid leukemia (post-MDS AML), and its role in pathogenesis or progression of MDS and post-MDS AML. METHODS Expression of Evi-1 and MDS1-Evi-1 genes was examined in 31 MDS, 11 post-MDS AML, and 34 de novo AML patients by a semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). RESULTS Evi-1 expression was not detected in bone marrow samples of 8 normal controls, but low MDS1-Evi-1 expression levels (MDS1-Evi-1/GAPDH<0.1) were detected in 3 of the 8 controls. Evi-1 RNA was expressed in 1 of 8 RA, 8 of 13 RAEB and 6 of 9 RAEB-T patients, and the percentage of Evi-1 expression in RAEB(T) patients was higher than that in RA (P<0.05). MDS1-Evi-1 expression was detected in 5 of 8 RA, 9 of 13 RAEB and 5 of 9 RAEB-T patients, and MDS1-Evi-1 expression levels (MDS1-Evi-1/GAPDH>0.1) were markedly higher than those in the controls. Evi-1 expression was gradually increased in 4 of 5 RAEB-T patients with transformation from MDS to AML. The percentages of Evi-1 and MDS1-Evi-1 expression in post-MDS AML patients were significantly (P<0.01 and P<0.05 respectively) higher than those in de novo AML. The colonies of hematopoietic progenitor cells were decreased in Evi-1 and MDS1-Evi-1-positive MDS patients as compared with those in Evi-1 and MDS1-Evi-1-negative patients. CONCLUSIONS Abnormal expression of the Evi-1 gene and overexpression of MDS1-Evi-1 gene may play a role in the pathogenesis or progression of MDS and post-MDS AML.

OBJECTIVE To induce islet grafting tolerance by intravenous injection of anti-CD4, anti-CD8 immunotoxins and donor soluble antigen. METHODS Fourteen days or 7 days prior to transplantation, the immunotoxin of anti-CD4, anti-CD8 200 micrograms respectively, and donor soluble antigen 500 micrograms were intravenously injected and then 500 donor islets were transplanted under the left renal subcapsular space of diabetes recipients (Sprague-Dawley rats). RESULTS The islet grafting survival time for those recipients pretreated with immunotoxin and donor soluble antigen was>60 days (P<0.01). The immunotoxins, donor soluble antigen treatment alone might only slightly prolong the grafting survival time. CONCLUSIONS The anti-CD4, anti-CD8 immunotoxins jointly used with donor soluble antigen can induce donor specific immunotolerance.

OBJECTIVE To observe the time of spontaneous activation of hamster oocytes and to find out the early signs of hamster oocytes activation. METHODS First, 63 hamster oocytes including activated and non-activated oocytes (group A) and 51 non-activated oocytes (group B) were injected with human sperm and checked for fertilization after 16-18 hours. Then, 20 hamster oocytes were cultured in vitro in medium with or without calcium and examined under light microscope every half an hour up to 9 hours. RESULTS Under light microscope, hamster oocytes activation were observed to undergo 4 stages: metaphase II stage without meiotic spindle, appearance of meiotic spindle near the first polar body, protrusion of oolemma, and complete extrusion of second polar body with pronucleus formation. After culture for 1.5 hours in vitro, 30%-40% of the oocytes demonstrated meiotic spindle; but after 9 hours, 50% showed complete activation. Culture in medium without calcium showed a little delay in the process of activation. The earliest sign of spontaneous activation in hamster oocytes was the appearance of meiotic spindle near the first polar body. Although group A and B showed no difference, the damage rate was lower in group B (19.7%±16.6%) than in group A (35.9%±5.7%) (P = 0.08), whereas the fertilization rate (18.3%±10.9%) was higher in group B than in group A (14.2%±8.7%) (P = 0.135). CONCLUSIONS Hamster oocytes may be activated spontaneously early after their removal. It is important to recognize the earliest sign of spontaneous activation and perform intracytoplasmic sperm injection (ICSI) before it happens.

OBJECTIVE To analyse comparatively the relevant data from bone tumor registries in China, Japan, and the United States. METHODS The data of 38,959 histologically confirmed primary bone tumors collected by the Chinese Bone Tumor Registry 1957-1988, 20,272 collected by the Japanese Bone Tumor Registry 1972-1990, and 11087 diagnosed and treated at Mayo Clinic, USA were used for comparative analysis by race, age, sex and skeletal distribution. For reliability, we used ratios of different tumors to osteosarcoma for frequency analysis. We also included some data from the SEER 1973-1987 as well as from Memorial Sloan-Kettering Cancer Center, USA. RESULTS The relative frequency of osteosarcoma (OS) is higher in China and Japan than in the United States. There were only limited number of OS patients aged over 50 years in Chinese and Japanese groups, which might be due to the lower incidence of OS subsequent to Paget's disease in Asians. More osteosarcoma occurred in the flat bones in the Americans than in the Chinese and Japanese. The relative frequency of chondrosarcoma (CS) was higher in the American group than in the Asian groups. The average age of CS patient was younger in the Chinese than in the Japanese and the Americans. The data confirmed the previous report that the incidence of Ewing sarcoma was higher in western people than in Asians. The data showed that the comparative frequency of chordoma is higher in the Americans than in the Asians and that the incidence of giant cell tumor of bone is higher in the Chinese and Japanese than in the Americans. CONCLUSIONS The findings from this analysis provide useful information for the epidemiologic study and the clinical diagnosis of bone tumors.

Purpose To understand the potential interaction between antiarrhythmic therapy and the implantable cardioverter-defibrillator (ICD) in patients who receive pharmacologic therapy as an adjunct to ICD therapy. Data source MEDLINE searching was employed and the information was indexed from approximately 3600 journals published world-wide from 1966 to 1998. Study selection and data extraction Data were collected from 66 of approximately 455 originally identified articles and abstracts using explicit methodological criteria. Results The ICD therapy has been widely used for therapy of life-threatening ventricular arrhythmias (VT/VF) and prevention of recurrence of sudden cardiac death. Studies reported that 40%-70% or 10%-40% of ICD patients required concomitant antiarrhythmic medication to reduce the frequency of sustained arrhythmic episodes and to minimize the frequency of device discharges. Most studies on antiarrhythmic drug-ICD interactions have been performed in experimental animals. Antiarrhythmic drugs can influence the effectiveness of ICD to terminate arrhythmias through their effects on defibrillation threshold (DFT). Studies have demonstrated a rise in DFTs with class Ib agent lidocaine and class Ic agents encainide and flecainide. Class Ia agents, as well as amiodarone, bretylium and propafenone may have more variable effects on DFT probably because of the difference between acute and chronic drug dosing, dose-related changes, active metabolites, and reproducibility in determining DFT. Class Ⅲ agents, with the exception of amiodarone, consistently decrease DFT. These drugs can be used as front-line agents in ICD patients. CONCLUSIONS Antiarrhythmic drugs can increase, decrease, or have no effect on DFT. Class Ⅲ agents except amiodarone can be safely administered in conjunction with ICD patients as long as the interaction between these therapeutic modalities is appreciated.