Acute leukemia associated with the t(4;11) chromosome rearrangement: ultrastructural and immunologic characteristics

The acute leukemia associated with the t(4;11) chromosome rearrangement is characterized by relatively consistent clinical features: occurrence primarily in young individuals, hyperleukocytosis, and poor response to therapy. This study describes the morphological, ultrastructural, and immunologic characteristics of the leukemic cells from ten patients with this type of leukemia. The morphological features of the leukemic blasts vary from lymphoid-appearing to monocytic. Ultrastructurally and cytochemically, some of the lymphoid-appearing blasts possess features of myeloid origin. The immunologic phenotype is characteristically E- SIg- CALLA- BA-1- BA-2+ HLA-DR+ and TdT+. These findings suggest that the t(4;11)-associated acute leukemia represents a proliferation of an early myeloid progenitor cell.     

High molecular weight kininogen: localization in the unstimulated and activated platelet and activation by a platelet calpain(s)

High mol wt kininogen (HMWK), the major cofactor-substrate of the contact phase of coagulation, is contained within and secreted by platelets. Studies have been performed to localize platelet HMWK in both the unstimulated and activated platelet and to ascertain the effect of platelet enzymes on HMWK itself. On platelet subcellular fractionation, platelet HMWK was localized to alpha-granules, and platelets from a patient with a deficiency of these granules (gray platelet syndrome) had 28% normal platelet HMWK. Platelet HMWK, in addition to being secreted from the platelet, was also localized to the surface of the platelet when activated. Using a competitive enzyme- linked immunosorbent assay for HMWK as an indirect antibody consumption assay, the external membrane of thrombin-activated platelets as well as the releasate from these stimulated platelets had 17 ng HMWK antigen/10(8) platelets available, whereas unstimulated platelets and their supernatant had only 4.9 and 4.2 ng HMWK/10(8) platelets present, respectively. The anti-HMWK antibody consumption by activated normal platelets was specific for membrane-expressed platelet HMWK, since activated platelets from a patient with total kininogen deficiency did not adsorb the anti-HMWK antibody. Enzymes in the cytosolic fraction of platelets cleaved 125I-HMWK (mol wt 120,000) into a mol wt 100,000 polypeptide as well as smaller products at mol wt 74,000, mol wt 62,000, mol wt 47,000, and a few components below mol wt 45,000. No cleavage products were observed when DFP and leupeptin were present. The cleavage of HMWK was specifically prevented by inhibitors of calcium-activated cysteine proteases (leupeptin, N-ethylmaleimide, iodoacetamide, and EDTA) but not by inhibitors of serine proteases (DFP, benzamidine, soybean trypsin inhibitor, or aprotinin). Platelet cytosol increased the coagulant activity of exogenous purified HMWK with maximum HMWK coagulant activity (35-fold) occurring within ten minutes of exposure to platelet cytosol. Treatment of platelet cytosol with leupeptin prevented the increase in the coagulant activity of exogenous HMWK. These studies indicate that activated platelets express platelet HMWK on their external membrane and platelet enzymes can cleave and increase the coagulant activity of exogenous HMWK.     

Role of arginine residues in the coagulant activity of high molecular weight kininogen

High molecular weight (HMW) kininogen, the cofactor for activation of the contact system of plasma proteolysis, transports and optimally positions prekallikrein and factor XI on a negatively charged surface, allowing those zymogens to be activated by surface-bound factor XIIa. HMW kininogen circulates in plasma as a procofactor that, after cleavage by kallikrein or factor XIIa, gains ability to bind to the surface. The mechanism responsible for this increased affinity for the surface is unknown. We hypothesized that modification of arginine residues may prevent cleavage of HMW kininogen, since the initial kallikrein-induced cleavage sites on the HMW kininogen molecule are at the NH2 terminal and the COOH terminal of the bradykinin-containing portion of the molecule, each of which contains arginine. We found that modification with butanedione of four arginine residues in the HMW kininogen molecule prevented bradykinin release, which results from cleavage of HMW kininogen. Furthermore, HMW kininogen coagulant activity was lost, in proportion to the degree of arginine modification, until 6.6 residues had been modified. Complex formation with prekallikrein, however, was found to be uneffected by the modification of modified HMW kininogen. To account for the loss of coagulant activity, we also examined the ability of modified HMWKa (active cofactor) to bind to an activating surface. The affinity of modified HMWKa for kaolin was tenfold less than the affinity of unmodified HMWKa. These data suggest that arginine residues play a critical role in the ability of HMW kininogen to function as an activation cofactor, both by preventing the cleavages that produce HMWKa as well as by decreasing the affinity of HMWKa for the surface.     

Factor V is activated and cleaved by platelet calpain: comparison with thrombin proteolysis

Platelets are known to process human factor V during secretion and/or membrane binding. We studied the functional and structural changes produced in human factor V by purified human platelet calpain (calcium- activated thiol protease) and compared the alterations with those induced by thrombin. A maximum increase in coagulant activity of 2.5- fold was observed when factor V (1 U/mL, 33 nmol/L) was incubated with calpain (0.03 U/mL, 2.7 nmol/L) in comparison with a 8.8-fold increment for alpha-thrombin (0.7 U/mL, 8 nmol/L) at 25 degrees C. Thrombin additions to reactions initiated by calpain resulted in further activation comparable to that of thrombin alone, whereas the subsequent addition of calpain had no effect on the extent or pattern of the activation of factor V by thrombin. The cleavage pattern of factor V produced by these two enzymes are distinctly different. Although thrombin activation eventually results in four final components designated C1 (150 kd), D (105 kd), E (71 kd), and F1F2 (71 to 74 kd), calpain yields initial components of 200 kd and 160 kd within one minute. Further digestion of the 200 kd species by calpain gives rise first to a polypeptide of 160 kd that is converted to a 140 kd and a 120 kd species by two minutes with an increase in coagulant activity. Immunoblotting of these fragments with the monoclonal antibody (MoAb) B10 directed to factor V and the thrombin-generated C1 fragment yields results demonstrating a common epitope in these calpain-generated components of 200, 160, 140 and 120 kd. The degradation of the initial 160 kd polypeptide gives rise to polypeptides of 100 and 65 kd, both undetectable on immunoblotting with MoAb B10. The 130, 87, 58, and 48 kd components are of less certain origin. Thus, platelet calpain generates a complex but reproducible cleavage pattern different from thrombin that may explain the partial activation observed. Nevertheless, calpain processing may play a role in early hemostatic reactions involving platelets before the appearance of the first thrombin molecule.     

Eating practices and behavior in the urban environment: a study in downtown São Paulo

This study focuses on the implications of urban life style on eating habits and the related symbolic representations. Theoretical references used to approach the food experience are the concepts of social representation and habitus. The methodology consisted of a qualitative analysis of interviews with 21 administrative employees and field observations made at commercial establishments in downtown S?o Paulo, such as snack bars and restaurants. Study of eating behavior and practices was developed along two planes: food actually eaten and food desired. Results were classified into three segments: "ingesting and digesting affection", "determinants of social representations of eating practices", and "rituals in eating practices". Due to their origin in a domestic universe, symbolic aspects associated with food have a strong affective matrix. Concrete conditions of the urban environment associated with the subject's financial limits establish a structure of values and feelings compatible with the subject's possibilities. The study addresses both the abbreviation of food rituals and its implications on food behavior as well as features of the present urban food pattern.     

Does a single control mechanism exist for both forward and backward walking?

It has been proposed that the highly reproducible forward walking (FW) locomotor pattern is generated by a central neuronal program or central pattern generator (CPG) which provides the underlying mechanism which produces the coordinated walking movement. The purpose of this study was to quantify the differences in the muscular activation patterns during FW and backward walking (BW) at a constant step frequency and to determine if common features exist across both locomotor conditions. The hypothesis was that FW and BW are both mediated by the same CPG; therefore, only small modifications in the CPG are required in order to produce the different characteristics of each walking mode. The results noted kinematically reversed patterns at the hip and ankle joints between FW and BW. The knee joint movement pattern was similar between conditions, however, a phase shift of 14.3% of the gait cycle occurred. An approximately 25% phase shift in the muscle activation patterns existed between FW and BW in four of the six muscles studied. Additionally, a pattern recognition technique was applied to the combined EMG signals to determine the minimum number of features required to generate the measured muscular output. Only two main features were necessary to produce the EMG patterns for both the FW and BW condition. The main features in FW were more consistent than noted in BW. The results support the notion that a single spinal mechanism such as a CPG with two main features appears to be in control during both FW and BW.     

Multiple glomus tumor: a case report and review of the literature.

Multiple glomus tumors are extremely rare and differ from the more common solitary glomus tumors in their clinical presentation and histological features. The authors report a case of multiple glomus tumors of the right hand in a 65-year-old man, its treatment, and a review of the features of this uncommon tumor. The tumor usually presents as a painful, firm, purplish, solitary nodule of the extremities, especially in the nail bed. Multiple glomus tumors are described as softer, more compressible, bluish nodules and they occur with less frequency than solitary tumors. They are often inherited in an autosomal dominant pattern. The authors present a case of multiple glomus tumors of the right hand, in which many small, painful, red papules were grouped in the right hypothenar region. The patient was treated by wide excision of the lesion and coverage of the defect with an ulnar artery forearm flap.     

胚胎嗅鞘细胞移植治疗脑性瘫痪：4例术后4周结果报告

目的:观察胚胎嗅鞘细胞移植治疗脑性瘫痪的有效性和安全性。方法:①病例资料:4例因出生时缺血缺氧确诊为脑性瘫痪的患者,男2例,女2例,年龄分别为14岁、岁、个月、岁。嗅92817鞘细胞由北京市虹天济神经科学研究院细胞中心提供,实验经医学伦理委员会批准,4例脑性瘫痪患者均签署知情同意书。②实验方法:根据术前MRI或CT片,患者均在局麻下行微创立体定向嗅鞘细胞移植术,选取双额放射冠为注射靶点,每侧注射1.0×106个细胞。术后给予止血、抗感染、康复等常规处理。③实验评估:分别于嗅鞘细胞移植前、移植后4周采用脑瘫综合功能评定量表、脑瘫日常生活能力量表评价患者神经功能及生活质量的改善。结果:①嗅鞘细胞移植术后4周,4例患者较术前均有不同程度的神经功能改善,未出现手术并发症。②脑瘫综合功能评定总分:病例1由92.5分增至94分,病例2由55分增至56分,病例3由10.5分增至11.5分,病例4由9.5分增至13分。③脑性瘫痪日常生活能力量表总分:病例1由82.0分增至83.5分,病例2无变化,为16.5分,病例3由5.0分增至7.5分,病例4由5.0分增至8分。结论:嗅鞘细胞移植治疗脑性瘫痪患者近期评价安全可行,可部分改善神经功能与生活质量,长期效果有待进一步随访。     

女性慢性下腹痛的干预性治疗

1背景 育龄妇女常见慢性下腹痛，可造成身体损害、情绪忧伤及导致巨大的健康服务费用。美国在这方面的花费超过8亿8千万美元（Mathias 1996）。英国全国数据库的一般性诊治资料显示，慢性下腹痛发病率及流行率与偏头痛、背部痛、哮喘发病率相似（Zondervan 1999）。