胚胎发育潜能的评估及其研究进展

在体外受精一胚胎移植（IVF—ET）技术中，人类的配子和胚胎存在大量浪费的现象，如约20％的卵子不受精、约35％的胚胎被直接作为废弃胚胎而丢弃、约60％胚胎在体外培养过程中不能发育到囊胚。即使胚胎被移植入子宫，也是大部分不能着床。人类胚胎的低利用率除了与超排卵、体外培养、胚胎评估、选择方法和内膜容受性等有关外，还与人类自身的生理状况相关。在自然状态下，生育年龄妇女每周期的妊娠率也仅为25％～35％，而流产率则高达10％～15％。     

注射用血栓通对实验性肝损伤的防治作用及其机制

目的 本研究旨在观察注射用血栓通对肝损伤的防治效果,并初步探讨其发挥药效的机制.方法 将0.6 mmol/L的H2O2加入到10-7～102μg/ml的经注射用血栓通预处理HepG2细胞中,四甲基偶氮唑盐(MTT)观察细胞活力;10% CCl4腹腔注射于经注射用血栓通(50 mg/kg、5 mg/kg、0.5 mg/kg)预处理的SD大鼠,于注射CCl4的24、48、72 h动态观察大鼠血清ALT、AST、TBil的变化,并于实验结束取大鼠肝组织进行组织学检查;HepG2细胞经10-3μg/ml注射用血栓通作用48 h,提取mRNA,逆转录成cDNA,与芯片杂交,根据基因芯片杂交信号强弱筛选相关基因.结果 注射用血栓通处理的HepG2细胞受到H2O2损伤时能够维持细胞的活力状态;注射用血栓通可以抑制CCl4造成肝损伤时血清ALT、AST、TBil的升高,并减轻肝损伤时大鼠肝组织的病理改变;注射用血栓通的肝细胞损伤保护作用可能与上调肝细胞损伤修复基因有关.结论 注射用血栓通能够抑制H2O2造成的肝细胞损伤,抑制CCl4造成的大鼠肝损伤,其机制可能与其上调某些损伤修复基因的表达及/或下调某些损伤相关基因表达有关.     

Influence of preexistent pyelonephritis on the development and manifestations of acute fatal glomerulonephritis

In a 39-year-old woman suffering for five years from chronic pyelonephritis with a stationary course, a sudden lethal renal failure occurred after an intercurrent febrile respiratory disease. The autopsy revealed scarred pyelonephritic kidneys with swollen hypertrophic areas. Microscopically, in sclerotic segments the glomeruli either were preserved or exhibited only various stages of vascular atrophy. Outside the pyelonephritic areas, however, massive subacute extra-intracapillary glomerulonephritis with typical crescents was apparent. — The role played by preexistent renal lesion in the pathogenesis of glomerulonephritis, and some problems involved in the diagnosis of coexistent glomerulo- and pyelonephritis, are discussed.     

Palatogenesis and potential mechanisms for clefting

This review concentrates on mechanisms of palatogenesis. This includes theories of shelf elevation, the role of matrix and identification of molecules and growth factors, which have key roles. The areas where failure to develop could potentially lead to clefting are highlighted. A key part of shelf fusion is the breakdown of the medial edge epithelium, a process that is probably dependent on enzymes involved in matrix turnover. There is good evidence that the matrix metalloproteinases may provide a common link to the multiple genetic and environmental factors that are known to cause clefting.     

The right heart and its distinct mechanisms of development, function, and failure

Congestive heart failure is the most common cause of hospitalization in the United States for people over the age of sixty-five. As the population ages, the morbidity and mortality from heart failure will become more prevalent. Left heart failure has been, and continues to be, extensively studied. However, a recent report from the National Heart, Lung, and Blood Institute suggests that the right heart has been relatively under-investigated, and unfortunately, most of the basic mechanisms of intracellular signaling within the right heart still remain poorly understood. Right heart failure is now being increasingly recognized as distinctly different from left heart failure, and an important mediator of overall cardiovascular collapse. The purpose of this review, therefore, is to discuss the current understanding of right heart cellular development, physiology, and pathophysiology, as well as to review therapeutic interventions that are both currently available and under investigation.     

Clinical development of immunotherapy for prostate cancer

Prostate cancer is the most common cancer in men, and the second leading cause of cancer‐related death in Western countries. Prostate cancer‐related death occurs in patients with metastatic castration‐resistant prostate cancer. Although several new drugs for castration‐resistant prostate cancer have been approved, each of these has prolonged survival by just a few months. Consequently, new therapies are sorely needed. Recently, it has been recognized that immunotherapy is an effective treatment for prostate cancer patients. Several strategies, such as cancer vaccines and immune checkpoint inhibitors, have been investigated in clinical studies for prostate cancer patients. In the present review, the results of the most recent clinical studies investigating immunotherapy in prostate cancer patients are reported, and the future clinical development of immunotherapy for prostate cancer is discussed.     

LAK cell adoptive immunotherapy and its problems

Clinical efficacy of lymphokine-activated killer (LAK) cell adoptive immunotherapy (AIT) in combination with plasma exchange and interleukin (IL-2) was investigated in 24 patients with advanced cancer. Partial response (PR) was found in 4 patients (20%), including 1 primary liver tumor, 1 metastatic lung tumor from renal cancer and 2 malignant pleural effusions from gastric and lung cancer. Based on these results new AIT in combination with plasma exchange, OK-432, IL-2 and cyclophosphamide was designed to target liver and lung tumors, in which LAK cells and other drugs were administered through the catheter located in the feeding artery of the tumor. Out of ten patients treated, 1 (10%) with metastatic liver tumor from gallbladder cancer was evaluated as PR. It is suggested that a strategy to enhance tumor accumulation and recognition of LAK cells should be attempted for development of gastrointestinal cancer therapy with AIT.     

Pneumoscrotum: report of two cases and review of mechanisms of its development.

Scrotal emphysema and, less frequently, pneumatocele are uncommon signs of pneumoscrotum caused by a variety of pathogenic and iatrogenic disease processes. The finding of air in the scrotal sac may be an early sign of a life-threatening condition or may represent an incidental finding associated with more benign conditions. The three basic mechanisms by which air becomes localized to the scrotum are discussed, the literature is reviewed, and 2 new cases are presented.     

Frequency of development of early cortical scarring in acute primary pyelonephritis

Fifty-five cases of primary (that is, without urinary tract abnormalities), acute pyelonephritis (PN) were studied by computed tomodensitometry (CT). There were 48 women and 7 men. All were febrile and 16 had positive blood cultures. In 7 cases, (4 diabetics and 3 malnourished alcoholics) PN was painless, diagnosis was delayed and lesions were severe. Two diabetics underwent emergency nephrectomy for sepsis. Conventional radiological techniques (IVP and ultrasonography) were poorly informative. In contrast, initial CT abnormalities were visible in 44 patients. They consisted of triangular or round hypodense images, diffuse hypodensity in a grossly swollen kidney, and/or abscesses. Hypodense images were presumably due to acute focal ischemia. Renal histology was available in five patients. It showed acute interstitial nephritis with leukocyte infiltrates, edema and hemorrhagic streaks. Pyelonephritis was due to E. coli in 48 cases (87.5%). In 27 cases E. coli isolates were studied by genotypic assays which detect the three most frequent (pap, afa and sfa) of the four operons known to encode adhesin. In all cases, at least one of these genotypic markers of uropathogenicity was found. In 27 cases, repeat CT was done shortly after treatment. It showed healing in only 12. Early cortical scar formation was visible in 2. Final evaluation in 27 cases with adequate follow-up showed that (in addition to the 2 patients who had been nephrectomized), in only 17 of 27 (63%) had the kidneys recovered a normal appearance. In two cases one kidney had undergone atrophy; renal biopsy showed subacute-chronic interstitial nephritis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Immunopathological studies of the ruptured human renal allograft.

The immunopathology of five cases of spontaneous allograft rupture has been studied. All kidneys were edematous on exploration and routine histological sections showed interstitial edema and mononuclear cell infiltration characteristic of acute rejection. Immunofluorescence revealed, at most, scattered vascular deposition of IgM and mild mesangial C3 deposition. These findings are compared with findings in normal kidneys and kidneys which had been hyperacutely rejected. The normal kidney showed focal afferent arteriolar and proximal mesangial stalk deposition of C3 without IgM. The kidneys of patients with hyperacute rejection showed brilliant staining for fibrin and IgM in all arterial and arteriolar walls with lesser amounts of C3 and IgG; IgM and C3 were prominent in the glomerulus. These findings suggest that mechanisms other than circulating preformed antibodies are responsible for the pathogenesis of spontaneous allograft rupture.     

Transfer factor: A potential agent for immunotherapy of cancer

Transfer factor (TF) is an extract from human leukocytes which has been shown to transfer specific skin test reactivity to previously nonreactive human recipients, and to produce measurable increases in in Vitro tests of lymphocyte activity. The results of the experimental use of TF as an immunotherapeutic agent for cancer are reviewed. TF therapy has been associated with tumor regression, temporary stabilization or reduced need for other treatment modalities in several reported cancer patients, and may have value as an adjuvant therapy in certain malignancies. However, most of the reports involve uncontrolled studies, and no agreement exists about the definition of TF donors. Controlled studies and the use of well characterized TF donors are essential before any conclusions can be drawn about the value of TF in the therapy of cancer and other diseases.

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Résumé Le facteur de transfert (TF) est un extrait de leucocytes humains. Il a été démontré qu'il transfère à l'homme anergique une capacité de réaction cutanée spécifique et qu'il augmente la réponse des tests d'activité lymphocytaire in vitro. Le TF a été utilisé, à titre expérimental, pour l'immunothérapie anticancéreuse. Dans plusieurs cas, l'administration de TF a été suivie de régression de tumeurs, de stabilisation temporaire, et l'on a également observé qu'il était possible, sous TF, de réduire les autres besoins thérapeutiques. Le TF est donc peut-Être valable en tant que thérapeutique adjuvante de certains cancers. Cependant, la plupart des travaux publiés sont des études non contrÔlées, et il n'existe aucun accord quant aux critères de définition du donneur de TF. Il sera impossible de tirer des conclusions quant à la valeur des traitements par TF dans le cancer ou d'autres maladies, aussi longtemps que des études contrÔlées n'auront pas été réalisées et que les caractères des donneurs de TF ne seront pas définis.

     

Acute graft pyelonephritis: a potential cause of acute rejection in renal transplant

Acute graft pyelonephritis is a common complication in renal transplant recipients. The consequences of this complication on kidney allograft survival remain controversial. Bacterial infection is likely to activate the immune system, potentially leading to acute or chronic rejection. Here, we report for the first time two documented cases of acute rejection occurring shortly after acute graft pyelonephritis, suggesting that pyelonephritis can initiate acute rejection. The immunologic process leading to the alloimmune response is discussed. These reports suggest that acute rejection should be questioned in case of atypical graft outcome in the context of acute graft pyelonephritis.     

慢性肾衰竭中的血脂代谢异常及其后果

慢性肾衰竭（CRF）中心血管疾病的发生及死亡率显著增加。近年来脂质代谢在CRF中的作用越来越受到重视,大量的研究探讨了CRF时脂质代谢异常的特征及发病机理。本文拟在对CRF时脂质代谢异常的特征,分子机理和可能的后果作一综述。     

Molecular mechanisms of renal development

The biology of renal development has become increasingly complex because technical advances in genetics and cell biology have been used to study this aspect of embryogenesis. The molecular biology and genetics of renal development may seem inconsequential and frustrating to the practicing clinician, but insight into fundamental mechanisms of renal development are necessary to understand clinical breakthroughs that will occur in the future. As a basis for appreciating these concepts, specific paradigms of renal development are illustrated and the investigative strategies used to develop them are summarized in this article.     

Ischaemic preconditioning: mechanisms and potential clinical applications

Purpose

Brief ischaemic episodes, followed by periods of reperfusion, increase the resistance to further ischaemic damage. This response is called “ischaemic preconditioning.” By reviewing the molecular basis and fundamental principals of ischaemic preconditioning, this paper will enable the anaesthetic and critical care practitioner to understand this developing therapeutic modality.

Source

Articles were obtained from a Medline review (1960–1997; search terms: ischaemia, reperfusion injury, preconditioning, ischaemic preconditioning, cardiac protection). Other sources include review articles, textbooks, hand-searches (Index Medicus), and personal files.

Principle finding

Ischaemic preconditioning is a powerful protective mechanism against ischaemic injury that has been shown to occur in a variety of organ systems, including the heart, brain, spinal cord, retina, liver; lung and skeletal muscle. Ischaemic preconditioning has both immediate and delayed protective effects, the importance of which varies between species and organ systems. While the exact mechanisms of both protective components are yet to be clearly defined, ischaemic preconditioning is a multifactorial process requiring the interaction of numerous signals, second messengers and effector mechanisms. Stimuli other than ischaemia, such as hypoxic perfusion, tachycardia and pharmacological agents, including isoflurane, have preconditioning-like effects. Currently ischaemic preconditioning is used during minimally invasive cardiac surgery without cardiopulmonary bypass to protect the myocardium against ischaemic injury during the anastomosis.

Conclusion

Ischaemic preconditioning is a powerful protective mechanism against ischaemic injury in many organ systems. Future clinical applications will depend on the clarification of the underlying biochemical mechanisms, the development of pharmacological methods to induce preconditioning, and controlled trials in humans showing improved outcomes.