异基因造血干细胞移植后共刺激分子LIGHT/HVEM的表达与GVHD的关系

目的 探讨异基因造血干细胞移植(allo-HSCT)后共刺激分子LIGHT和HVEM的表达与移植物抗宿主病(GVHD)发生的关系.方法 26例allo-HSCT患者中,预处理方案采用环磷酰胺+足叶乙甙+全身照射11例,采用氟达拉滨+阿糖胞苷+白消安12例,采用环磷酰胺3例.移植时,输注单个核细胞(5.89±3.36)×10~8/kg,CD34~+细胞(3.29±1.29)×10~6/kg.预防急性GVHD(aGVHD)的方案采用环孢素A+短程甲氨蝶呤+吗替麦考酚酯,HLA半相合及非血缘关系者加用抗胸腺细胞球蛋白.GVHD的诊断与分级采用西雅图标准.在预处理前、移植后15 d、发生aGVHD时及aGVHD经治疗好转后分别采集患者外周血2 ml,采用三色流式细胞术进行检测,同时以15名健康志愿者的血液标本作为正常对照.结果 所有患者均获得造血功能重建,移植物均完全植活.移植后共发生aGVHD9例,发生率为35%,其中Ⅲ～Ⅳ度者3例,8例经治疗后好转,1例治疗无效死亡;发生慢性GVHD(cGVHD)7例,发生率为26.9%.患者预处理前和移植后15 d及正常人外周血T淋巴细胞几乎不表达LIGHT,组成性表达HVEM;发生GVHD时,LIGHT表达显著上调,HVEM表达下调;GVHD好转后,LIGHT和HVEM的表达恢复正常.移植后15 d时,发生aGVHD者LIGHT的表达高于未发生aGVHD者,而HVEM的表达较低(P<0.05).Ⅲ～Ⅳ度aGVHD者LIGHT的表达明显高于Ⅰ～Ⅱ度者(P<0.05).结论 LIGHT/HVEM在allo-HSCT后GVHD的发生和发展过程中起重要作用,通过监测该共刺激分子的表达对aGVHD的发生有一定预示作用.     

Sirolimus-based regimen promotes inhibitory costimulatory signal of HVEM/BTLA/CD160/LIGHT pathway in allo-renal recipients

HVEM/BTLA/CD160/LIGHT pathway is a very special costimulatory molecule system which can regulate T-cell immune responses by activating both inflammatory and inhibitory signalings. The regulatory effect of Sirolimus on HVME costimulatory system in allo-renal recipients has not been reported. In this study, we analyzed the expression of HVEM, BTLA, CD160 and LIGHT on circulating T cell subgroups and the expression of HVEM on CD4 + Tregs by flow cytometry and also the pre-dose concentration of Sirolimus by automatic analyzer. Both the allo-renal recipients receiving Sirolimus immunosuppressive regimen and health volunteers were included. The expression of both BTLA and CD160 on T cells increased significantly while the expression of LIGHT on T cells decreased significantly in allo-renal recipients receiving Sirolimus regimen (p < 0.05). The expression of HVEM on T cells and CD4 + T-cell subgroup decreased (p < 0.05) while that on CD8 + T-cell subgroup remained roughly normal (p > 0.05).The expression of HVEM on CD4 + Tregs increased significantly (p < 0.05) in allo-renal recipients receiving Sirolimus regimen (p < 0.05). Though regulating the expression of HVEM/BTLA/CD160/LIGHT costimulatory system, Sirolimus-based regimen promotes inhibitory costimulatory signal in T cells and enhances the function of CD4 + Tregs in allo-renal recipients, which are in benefit of the control of transplant rejection as well as the induction and maintenance of transplant tolerance.     

LIGHT/HVEM/LTβR Interaction as a Target for the Modulation of the Allogeneic Immune Response in Transplantation

The exchange of information during interactions of T cells with dendritic cells, B cells or other T cells regulates the course of T, B and DC‐cell activation and their differentiation into effector cells. The tumor necrosis factor superfamily member LIGHT (homologous to lymphotoxin, exhibits inducible expression and competes with HSV glycoprotein D for binding to herpesvirus entry mediator, a receptor expressed on T lymphocytes) is transiently expressed upon T cell activation and modulates CD8 T cell‐mediated alloreactive responses upon herpes virus entry mediator (HVEM) and lymphotoxin β receptor (LTβR) engagement. LIGHT‐deficient mice, or WT mice treated with LIGHT‐targeting decoy receptors HVEM‐Ig, LTβR‐Ig or sDcR3‐Ig, exhibit prolonged graft survival compared to untreated controls, suggesting that LIGHT modulates the course and severity of graft rejection. Therefore, targeting the interaction of LIGHT with HVEM and/or LTβR using recombinant soluble decoy receptors or monoclonal antibodies represent an innovative therapeutic strategy for the prevention and treatment of allograft rejection and for the promotion of donor‐specific tolerance.     

Blockade of LIGHT/HVEM and B7/CD28 signaling facilitates long-term islet graft survival with development of allospecific tolerance

BACKGROUND: Previous studies have shown that blockade of LIGHT, a T-cell costimulatory molecule belonging to the tumor necrosis factor (TNF) superfamily, by soluble lymphotoxin beta receptor-Ig (LTbetaR-Ig) inhibited the development of graft-versus-host disease. The cardiac allografts were significantly prolonged in LIGHT deficient mice. No data are yet available regarding the role of the LIGHT/HVEM pathway in more stringent fully allogeneic models such as skin and islet transplantation models. METHODS: Streptozotocin-induced chemical diabetic BALB/C mice underwent transplantation with allogeneic C57BL/6 islets and were treated with LTbetaR-Ig, CTLA4-Ig or a combination of both in the early peritransplant period. RESULTS: Administration of CTLA4-Ig or LTbeta R-Ig alone only increased graft survival to 55 days and 27 days respectively, whereas simultaneous blockade of both pathways significantly prolonged the islet allograft survival for more than 100 days. Long-term survivors were retransplanted with donor-specific (C57BL/6) islets and the grafted islets remained functional for more than 100 days. All of islet allografts were protected against rejection when the mixtures of 1x10(6) CD4+ T cells from tolerant mice and islet allografts were cotransplanted under the renal capsule of the na?ve BALB/c recipients. CONCLUSIONS: These data indicate that: 1) a synergistic effect for prolonged graft survival can be obtained by simultaneously blocking LIGHT and CD28 signaling in the stringent model of islet allotransplantation; 2) development of donor-specific immunological tolerance is associated with the presence of regulatory T-cell activity; and 3) local cotransplantation of the allografts with the regulatory T cells can effectively prevent allograft rejection and induce donor-specific tolerance in lymphocytes-sufficient recipients.     

Annual report of perioperative mortality and morbidity for the year 1999 with a special reference to anesthetic methods at Certificated Training Hospitals of Japanese Society of Anesthesiologists

The Committee on Operating Room Safety of Japanese Society of Anesthesiologists (JSA) sends annually confidential questionnaires of perioperative mortality and morbidity to Certificated Training Hospitals of JSA. This report is on perioperative mortality and morbidity in 1999 with a special reference to anesthetic methods. Four hundred and sixty-seven hospitals reported the number of cases referred to anesthetic methods and total numbers of cases were 727,723. The incidences of cardiac arrest per 10,000 cases due to all etiology are estimated to be 6.77 cases in average, 5.33 cases in inhalation anesthesia, 34.26 cases in total intravenous anesthesia (TIVA), 5.26 cases in inhalation anesthesia plus epidural or spinal or conduction block, 5.29 cases in TIVA plus epidural or spinal or conduction block, 0.73 cases in spinal with continuous epidural block (CSEA), 2.85 cases in epidural anesthesia, 1.63 cases in spinal anesthesia, 2.53 cases in conduction block and 46.51 cases in other methods. However, the incidences of cardiac arrest per 10,000 cases totally attributable to anesthesia are estimated to be 0.78 case in average, 0.51 case in inhalation anesthesia, 1.35 cases in TIVA, 0.97 case in inhalation anesthesia plus epidural or spinal or conduction block, 1.51 cases in TIVA plus epidural or spinal or conduction block, 0.73 case in CSEA, 1.71 cases in epidural anesthesia, 0.54 case in spinal anesthesia, 2.52 cases in conduction block and 1.08 cases in other methods. The incidences of severe hypotension per 10,000 cases due to all etiology are estimated to be 16.64 cases in average, 13.61 cases in inhalation anesthesia, 100.36 cases in TIVA, 13.32 cases in inhalation anesthesia plus epidural or spinal or conduction block, 9.07 cases in TIVA plus epidural or spinal or conduction block, 3.65 cases in CSEA, 6.26 cases in epidural anesthesia, 7.31 cases in spinal anesthesia, 2.52 cases in conduction block and 28.12 cases in other methods. On the other hand, the incidences of cardiac arrest per 10,000 cases totally attributable to anesthesia are estimated to be 2.40 cases in average, 1.65 cases in inhalation anesthesia, 0.81 cases in TIVA, 3.92 cases in inhalation anesthesia plus epidural or spinal or conduction block, 2.77 cases in TIVA plus epidural or spinal or conduction block, 2.56 cases in CSEA, 3.42 cases in epidural anesthesia, 2.71 cases in spinal anesthesia, zero case in conduction block and zero case in other methods. The incidences of severe hypoxia per 10,000 cases due to all etiology are estimated to be 5.32 cases in average, 6.7 cases in inhalation anesthesia, 9.17 cases in TIVA, 5.16 cases in inhalation anesthesia plus epidural or spinal or conduction block, 4.53 cases in TIVA plus epidural or spinal or conduction block, 2.56 cases in CSEA, zero case in epidural anesthesia, 1.08 cases in spinal anesthesia, zero case in conduction block and 1.08 cases in other methods. On the other hand, the incidences of severe hypoxia per 10,000 cases totally attributable to anesthesia are estimated to be 2.39 cases in average, 3.22 cases in inhalation anesthesia, 2.43 cases in TIVA, 2.26 cases in inhalation anesthesia plus epidural or spinal or conduction block, 2.77 cases in TIVA plus epidural or spinal or conduction block, zero case in CSEA, zero case in epidural anesthesia, 0.54 cases in spinal anesthesia, zero case in conduction block and 1.08 cases in other methods. The mortality rates of cardiac arrest per 10,000 cases due to all etiology are estimated to be 3.56 cases in average, 2.82 cases in inhalation anesthesia, 24.55 cases in TIVA, 1.4 cases in inhalation anesthesia plus epidural or spinal or conduction block, 1.51 cases in TIVA plus epidural or spinal or conduction block, zero cases in CSEA, 0.57 cases in epidural anesthesia, 0.27 cases in spinal anesthesia, zero case in conduction block and 42.18 cases in other methods. On the other hand, the mortality rates of cardiac arrest per 10,000 cases totally attributable to anesthesia are estimated to be 0.08 case in average, 0.09 case in inhalation anesthesia, 0.27 case in TIVA, 0.05 case in inhalation anesthesia plus epidural or spinal or conduction block, zero case in TIVA plus epidural or spinal or conduction block, zero case in CSEA, 0.57 case in epidural anesthesia, zero case in spinal anesthesia, conduction block and other methods. The outcomes of cardiac arrest totally attributable to anesthesia are 70.2% of full recovery without any sequelae, 10.5% of death within 7 days, 1.8% of vegetative state and 17.5% of unknown results while the outcome of critical events including severe hypotension and severe hypoxia totally attributable to anesthesia is 94.9% of full recovery without any sequelae, 0.4% of death within 7 days, 0.2% of vegetative state and 4.5% of unknown results. These results indicate that there are no differences in mortality and morbidity totally attributable to anesthesia among anesthetic methods in 1999 at Certificated Training Hospitals of Japan Society of Anesthesiologists.     

Declining Coronary Heart Disease Mortality in Iceland: Contribution by Incidence,Recurrence and Case Fatality Rate

Objective : To analyse to what extent the recent decline in coronary heart disease mortality in Iceland is due to changes in incidence, recurrence and case fatality rates. Design : A countrywide registration of myocardial infarction (MI) in people aged 25-74 was performed in Iceland during 1981-1999 according to the MONICA protocol. Possible cases were found by review of all hospital discharge records, autopsy records and death certificates. Results : MI death rate declined by 63% in males and 51% in females, most in the youngest age groups in men (86%) and least in the oldest (49%). In women there was not a significant difference in age groups. Overall the age-adjusted reduction in MI death rate was 55.4% in both sexes combined; of this 23.1% was due to incidence reduction, 22.8% to recurrence reduction and 11.6% to case fatality reduction. In the youngest age groups the decline in incidence contributed most to the decline in MI death rate (62% in men and 71% in women), but thereafter the decline in case fatality in men. In the older age groups decline in recurrence rate has greater weight. Conclusion : The recent decline in MI mortality under the age of 75 years in Iceland is due to reduction in incidence and recurrence rate by about 40% each and to reduction in case fatality by 20%.     

Inhibitory smads and tgf-Beta signaling in glomerular cells

Smad6 and Smad7 are inhibitory SMADs with putative functional roles at the intersection of major intracellular signaling networks, including TGF-beta, receptor tyrosine kinase (RTK), JAK/STAT, and NF-kappaB pathways. This study reports differential functional roles and regulation of Smad6 and Smad7 in TGF-beta signaling in renal cells, in murine models of renal disease and in human glomerular diseases. Smad7 is upregulated in podocytes in all examined glomerular diseases (focal segmental glomerulosclerosis [FSGS], minimal-change disease [MCD], membranous nephropathy [MNP], lupus nephritis [LN], and diabetic nephropathy [DN]) with a statistically significant upregulation in "classical" podocyte-diseases such as FSGS and MCD. TGF-beta induces Smad7 synthesis in cultured podocytes and Smad6 synthesis in cultured mesangial cells. Although Smad7 expression inhibited both Smad2- and Smad3-mediated TGF-beta signaling in podocytes, it inhibited only Smad3 but not Smad2 signaling in mesangial cells. In contrast, Smad6 had no effect on TGF-beta/Smad signaling in podocytes and enhanced Smad3 signaling in mesangial cells. These data suggest that Smad7 is activated in injured podocytes in vitro and in human glomerular disease and participates in negative control of TGF-beta/Smad signaling in addition to its pro-apoptotic activity, whereas Smad6 has no role in TGF-beta response and injury in podocytes. In contrast, Smad6 is upregulated in the mesangium in human glomerular diseases and may be involved in functions independent of TGF-beta/Smad signaling. These data indicate an important role for Smad6 and Smad7 in glomerular cells in vivo that could be important for the cell homeostasis in physiologic and pathologic conditions.     

软骨寡聚基质蛋白在慢性胰腺炎损伤中退变腺泡细胞内的表达

目的 研究正常胰腺、慢性胰腺炎与胰腺癌组织中软骨寡聚基质蛋白(cartilage oligomeric matrix protein,COMP)mRNA和蛋白表达水平的差异,揭示COMP在慢性胰腺炎样损伤中的意义。方法 采用Northern印迹法、Western印迹法、原位杂交法与免疫组化方法对14例慢性胰腺炎、14例胰腺癌及15例正常胰腺组织进行分析。结果 在慢性胰腺炎组织中和胰腺癌组织中类似慢性胰腺炎损伤的退变腺泡细胞胞浆内,存在高水平的COMP mRNA信号与免疫反应;而在胰腺癌细胞、正常胰腺组织的导管细胞与胰岛细胞的胞浆内,COMP mRNA信号与免疫反应微弱或缺如。结论 COMP在慢性胰腺炎及胰腺癌中类似慢性胰腺炎损伤的退变腺泡细胞内高表达,可能与慢性胰腺炎中腺泡细胞功能异常有关。     

Enflurane Improves the Oxygen Supply /Demand Balance in the Acutely Ischaemic Canine Myocardium

Acute myocardial ischaemia was produced in six dogs by ligation of the anterior descending branch of the left main coronary artery. Enflurane 1.5% inspired produced a significantly smaller reduction in blood flow in the ischaemic than in the non-ischaemic area in myocardium in the presence of a 46% reduction in mean arterial pressure. The improvement in oxygen availability/consumption ratio in the ischaemic in Comparison with non-ischaemic areas was attributed to a 16% reduction in heart rate.     

Calcium regulation by the chick embryo

An artificial air-chamber was produced in White Leghorn chick embryos on the eighth day of incubation. On day twenty, the concentration of calcium in blood and in yolk was found to be lower in the treated embryos than in controls but concentration in bone was similar in both groups. The histological and microradiographic aspect of bone was also similar in both experimental and control embryos. The decrease in the concentration of calcium in blood and in yolk indicates that the experimental procedure succeeded in producing a decrease in calcium intake by the embryo. The fact that bones remained unaffected tends to support the idea that in case of deficient supply of shell calcium, bones can withdraw the calcium they need from the yolk deposit.     

Endoscopy of the esophagus, stomach and duodenum at Victoria Hospital--Seychelles

From 1992-1995 in Victoria Hospital Republic of Seychelles 1037 patients undergone esophago-gastro-duodenoscopic examination. Ulcer was find in 26% patients, gastritis in 23.5%, gastroesophageal reflux in 15.9%, upper gastro-intestinal bleeding in 13.5%., carcinoma of the esophagus in 6%, gastric ulcer in 2.8%, hiatus hernia in 3%, esophageal varices in 2.1%, gastric carcinoma in 2.1% and 0.3% with polyps.     

Endovascular treatment of ruptured intracranial aneurysms using platinum coils in patients over 80 years of age

Endovascular treatment of intracranial aneurysms using plantinum coils was performed in 10 patients over 80 years of age. The patients ranged in age from 81 to 96 years. Preoperative Hunt and Kosnik grading revealed one patient in grade I, 4 in grade II, 3 in grade III, and 2 in grade IV. The aneurysms were located in the internal carotid artery in 6 patients, in the anterior communicating artery in 1, and in the middle cerebral artery in 3 respectively. Intra-aneurysmal occlusion was accomplished in 8 patients with total or subtotal occlusion in 6 and partial occlusion in 2. In one patient with a peripheral middle cerebral artery aneurysm, the parent artery was occluded just proximal to the aneurysm. In the remaining one patient in grade III, an aneurysm associated with wide neck could not be occluded because of coil protrusion into the parent artery. In 9 patients who were successfully treated, all five patients in grade I or II and one in grade III resulted in good outcome, but the other three patients in grade III and IV showed poor outcome. No evidence of recurrent hemorrhage was noted during the follow-up period ranging from 2 months to 4 years. Endovascular coil embolization is a useful therapeutic alternative for treating ruptured intracranial aneurysms in patients over 80 years of age, especially those in Grade I or II.     

退变颈椎间盘中胶原酶活性变化

目的 研究退变颈椎间盘中的胶原酶的活性变化。方法 通过切除实验动物颈棘上、棘间韧带及分离颈椎旁两侧肌肉,造成颈椎力学上的失衡而诱导了兔的颈椎间盘退行性变化。在术后３月和８月时分别处死３月组动物和８月组动物,取动物颈椎间盘组织,用生物化学方法测定其中胶原酶活性。结果 研究表明：（１）３月组实验组动物颈椎间盘中胶原酶活性明显高于３月对照组动物。（２）８月实验组动物颈椎间盘中胶原酶活性明显高于８月对照组     

Hemodynamics during laparoscopy in the supine or prone position

During laparoscopy elevations in arterial pressure and a decrease in cardiac output have been reported. Laparoscopic surgery performed in the prone position may be advantageous for some surgical procedures, but the hemodynamic effects of pneumoperitoneum in this position have not been studied. We studied the effects of different levels of increased intraabdominal pressure on hemodynamics and oxygen transport in eight pigs in the prone and the supine position. Increases in intraabdominal pressure did not result in decreased cardiac output or in a reduction of oxygen transport and consumption in either position. These results suggest that laparoscopy in the prone position does not result in more severe hemodynamic depression than laparoscopy in the supine position.     

CT-guided stereotaxic evacuation of hypertensive intracerebral hematomas]

CT-guided stereotaxic evacuation of hypertensive intracerebral hematomas was performed in 50 patients. Hematoma was found in the basal ganglion in 36 cases in the internal capsule in 23, in external capsule in 6, in thalamus in 7, in subcortex in 6 in cerebellum, in 6 and in brain stem in 2. The volume of these hematomas was less than 10 ml in 2 patients, 20-50 ml in 21, 51-100 ml in 16 and over 100 ml in 11. The liquid hematoma was totally aspirated by stereotaxic technique in 9 patients. Similarly, more than 80% of clots of hematoma was evacuated in 28 patients and about 60-80% of clots was evacuated in 13. Good operative results were obtained in 14 patients (28%). Mild neurological disability was seen in 16 patients (32%) and marked disability in 15 (30%). Five patients (10%) died.     

尿路复合性恶性肿瘤（附21例报告）

报告２１例尿路复合性恶性肿瘤，位于肾盂２例，膀胱１９例。主要临床表现为血尿，绝大多数病人伴有尿路刺激症状。低分化的移行细胞癌（ＴＣＣ）与继发性复合肿瘤有密切关系。２１例中１例为ＴＣＣ复合肉瘤，１１例为ＴＣＣ复合鳞癌，７例为ＴＣＣ复合腺癌，２例为腺癌复合鳞癌。本组２例肾盂肿瘤分别行肾输尿管全长加膀胱袖口状切除术和肾部分切除术，术后存活６个月和１年；膀胱肿瘤１４例行膀胱部分切除术，已生存３年４例，１年２例，未满１年２例，３例１～２年内死亡，失访３例；２例根治性膀胱全切术已生存５年和３年以上；３例行ＴＵＲＢｔ，已生存３年１例，１５年１例，未满１年１例。对尿路复合性恶性肿瘤的组织学、临床和病理特征进行了讨论。     

Distribution of thymic tissue in the mediastinal adipose tissue.

The distribution of thymic tissue in the anterior mediastinal, retrocarinal, and preaortic fat was examined histologically in 27 autopsy subjects. Thymic tissue was found in the anterior mediastinal fat in 12 subjects (44.4%), in the retrocarinal fat in two (7.4%), and in the preaortic fat in none. The finding of ectopic thymic tissue in these areas has not been reported previously, would appear to be surgically inaccessible via a median sternotomy, and may be responsible in part for some of the failures of thymectomy in the treatment of myasthenia gravis.     

Incidence of hip fracture in western Sweden 1974-1982. Comparison of rural and urban populations

Several epidemiological studies in northern Europe have shown that fractures in the elderly exceed the expected increase in the aging populations. We have compared the incidence of hip fracture in the rural county of Skaraborg and the city of G?teborg in Sweden. After adjustment for age changes in the population, the incidence of hip fracture in Skaraborg County was lower than in G?teborg during the period 1974-1984. The non-age-related increase in the incidence of fractures found in the city was not confirmed in the rural area.     

反复自然流产绒毛组织中前列腺素F_(2α)和白细胞介素-8的含量及其临床意义

目的　探讨反复自然流产患者绒毛前列腺素F2α(PGF2α)与血清和绒毛中白细胞介素 8(IL 8)的含量及其临床意义。　方法　分别应用放射免疫分析法和酶联免疫吸附法测定 3 0例反复自然流产患者 (病例组 )血清及绒毛组织PGF2α与IL 8的含量 ,以2 0例正常早期妊娠的人工流产孕妇作为对照。　结果　绒毛组织PGF2α含量病例组较对照组明显升高 (P <0 0 5) ;血清及绒毛组织IL 8含量病例组亦较对照组明显升高 (P <0 0 5) ;病例组血清及绒毛组织IL 8与绒毛组织PGF2α含量呈正相关。　结论　PGF2α与IL 8含量的升高在反复自然流产中起一定作用     

Treatment of benign bone tumours using external fixation

We present a retrospective study of patients suffering from a variety of benign tumours in whom external fixators were used to treat deformity and limb-length discrepancy, and for the reconstruction of bone defects. A total of 43 limbs in 31 patients (12 male and 19 female) with a mean age of 14 years (2 to 54) were treated. The diagnosis was Ollier's disease in 12 limbs, fibrous dysplasia in 11, osteochondroma in eight, giant cell tumour in five, osteofibrous dysplasia in five and non-ossifying fibroma in two. The lesions were treated in the tibia in 19 limbs, in the femur in 16, and in the forearm in eight. The Ilizarov frame was used in 25 limbs, the Taylor Spatial Frame in seven, the Orthofix fixator in six, the Monotube in four and the Heidelberg fixator in one. The mean follow-up was 72 months (22 to 221). The mean external fixation period was 168 days (71 to 352). The mean external fixation index was 42 days/cm (22.2 to 102.0) in the 22 patients who required limb lengthening. The mean correction angle for those with angular deformity was 23 degrees (7 degrees to 45 degrees ). At final follow-up all patients had returned to normal activities. Four patients required a second operation for recurrent deformity of further limb lengthening. Local recurrence occurred in one patient, requiring further surgery.