Creutzfeldt--Jakob Disease in Recipients of Human Growth Hormone in the United Kingdom: A Clinical and Radiographic Study

In the past 3 years there have been five further cases, in additionto one case reported in 1985, of Creutzfeldt-Jakob disease inrecipients of human growth hormone in the United Kingdom. Theclinical findings of two of these cases are described, demonstratinga typical presentation with a predominantly cerebellar syndromeat onset which is not commonly a presenting feature of sporadicCreutzfeldt-Jakob disease. In one case a ^99mTc hexamethylpropylenaminesingle photon emission tomographic scan showed marked impairmentof tracer uptake in the basal ganglia and cerebral cortex ata time when the clinical picture was predominantly cerebellar.This technique may be useful in early diagnosis. In the othercase post mortem examination of the brain showed prominent amyloiddeposition in the cerebellum, which has not been described previouslyin pituitary-hormone related Creutzfeldt-Jakob disease. Thepreviously published cases of growth hormone-related Creutzfeldt-Jakobdisease are reviewed and reasons for the particular clinicalpattern seen are discussed.     

Development of specific receptors for N-formylated chemotactic peptides in a human monocyte cell line stimulated with lymphokines

A human monocyte-like cell line, U937, when grown in continuous culture, does not secrete lysosomal enzymes or migrate towards chemotactic factors. When the cells are stimulated by lymphokines, however, they develop the ability both to migrate directionally and to secrete enzymes in response to several types of chemoattractants. The development, by stimulated cells, of chemotactic and secretory responses to one class of chemoattractants, the N- formylated peptides, is accompanied by the appearance on the cells of specific binding sites for these substances. Using tritiated N-formyl- methionyl-leueyl-phenylalanine (fMet-Leu-[(3)H]Phe) as a ligand, it was determined that unstimulated U937 cells possess no detectable binding sites. However, after stimulation with lymphocyte culture supernates for 24, 48, and 72 h, they developed 4,505 (+/-) 1,138, 22,150(+/-) 4,030, and 37,200 (+/-) 8,000 sites/cell, respectively. The dissociation constants for the interaction of fMet-Leu-[SH]Phe with the binding sites were approximately the same regardless of stimulation time and ranged between 15 and 30 nM. The binding of fMet-Leu-[(3)H]Phe by stimulated U937 cells was rapid and readily reversed by the addition of a large excess of unlabeled peptide. The affinity of a series of N-formylated peptides for binding to U937 cells exactly reflected the potency of the peptides in inducing lysosomal enzyme secretion and chemotaxis. The availability of a continuous human monocytic cell line that can be induced to express receptors for N-formylated peptides will provide a useful tool not only for the characterization of such receptors but also for the delineation of regulatory mechanisms involved in cellular differentiation and the chemotactic response.     

不同相对分子质量玻璃酸钠对膝关节镜术后关节功能恢复的作用比较

目的:观察关节腔内留置不同相对分子质量玻璃酸钠对膝关节镜术后早期疼痛及功能恢复的影响。方法:于2005-11/2006-05选择北京大学人民医院骨关节科收治的行膝关节镜手术患者60例。关节镜手术中根据不同诊断分别行半月板成形术、游离体取出术以及软骨成形术。60例患者按随机数字表法分为3个实验组,分别为Mr1.5×106～2.5×106玻璃酸钠组,Mr3×106玻璃酸钠组,Mr6×106玻璃酸钠组。术后关节腔内注入不同相对分子质量玻璃酸钠2.0～2.5mL,并被动屈伸膝关节20次,使玻璃酸钠均匀分布于关节内。术后第1天开始股四头肌力量锻炼,坐在床边屈膝活动,并可下床。术后1周拆除缝线,术后6周门诊复查。分别于术前、术后1,2,3d,1,6周采用同一评分量表进行自觉疼痛程度、日常生活活动能力、膝关节屈曲角度测评,评分越高,功能恢复越好。结果:纳入患者60例,均进入结果分析。①自觉疼痛程度测定:术后6周Mr1.5×106～2.5×106,3×106,6×106玻璃酸钠组自觉疼痛程度评分均高于术前[分别为(8.5±1.3),(7.3±2.2)分;(8.5±1.3),(7.3±2.2)分;(8.5±1.3),(7.3±2.2)分]。②日常生活活动能力测定:术后6周Mr1.5×106～2.5×106,3×106,6×106玻璃酸钠组日常生活活动能力评分均高于术前[分别为(60.5±8.4),(59.3±7.0)分;(63.4±8.2),(59.4±8.3)分;(66.9±3.8),(53.8±19.0)分]。③膝关节屈曲角度评分:术后6周Mr1.5×106～2.5×106,3×106,6×106玻璃酸钠组膝关节屈曲角度评分均高于术前[分别为(9.1±1.4),(5.8±2.7)分;(8.1±3.1),(7.2±3.5)分;(6.3±3.8),(5.5±3.1)分]。④综合评分:术后6周Mr1.5×106～2.5×106,3×106,6×106玻璃酸钠组综合评分均高于术前[分别为(88.1±7.7),(79.8±11.1)分;(91.4±6.8),(84.9±13.7)分;(91.2±10.7),(73.5±23.7)分]。关节腔内留置3种不同相对分子质量玻璃酸钠在膝关节镜术后近期各项评分差异均无显著性意义(P>0.05)。结论:关节腔内留置不同相对分子质量玻璃酸钠在膝关节镜术后近期康复中具有相似的效果。     

Care of post-traumatic spinal cord injury patients in India: An analysis

Background:

The spinal cord injured patients if congregated early in spinal units where better facilities and dedicated expert care exist the outcome of treatment and rehabilitation, can be improved. The objective of this study is to find out the various factors responsible for a delay in the presentation of spinal injury patients to the specialized spinal trauma units and to suggest steps to improve the quality of care of the spinal trauma patients in the Indian setup.

Materials and Methods:

Sixty patients of traumatic spinal cord injury admitted for rehabilitation between August 2005 and May 2006 were enrolled into the study and their data was analyzed.

Results:

Eighty-five per cent of the spinal cord injured patients were males and the mean age was 34 years (range 13-56 years). Twenty-nine (48.33%) of the spinal injuries occurred due to fall from height. There was an average of 45 days (range 0-188 days) of delay in presentation to a specialized spinal unit and most of the time the cause for the delay was unawareness on the part of patients and/or doctors regarding specialized spinal units. In 38 (62.5%) cases the mode of transportation of the spinal cord injured patient to the first visited hospital was by their own conveyance and the attendants of the patients did not have any idea about precautions essential to prevent neurological deterioration. Seventeen (28.33%) patients were given injection solumedrol with conservative treatment, 35 (60%) patients were given only conservative treatment and seven patients were operated (11.66%) upon at initially visited hospital. Of the seven patients operated five were fixed with posterior Harrington instrumentation (71.42%) and two (28.57%) were operated by short segment posterior pedicle screw fixation. None of the patients were subjected to physiotherapy-assisted transfers or wheel chair skills or even basic postural training, proper bladder/ bowel training program and sitting balance.

Conclusion:

Awareness on the part of the general population, attendants of the patients, clinical and paraclinical team regarding spinal cord injury needs to be addressed. Safe mode of transportation of spinal cord injured patient and early presentation at tertiary spinal care center with comprehensive spinal trauma care team should be stressed upon.     

Perfusion cell seeding and cultivation induce the assembly of thick and functional hepatocellular tissue-like construct

Developing advanced technologies for encouraging the ex vivo assembly of functional hepatic tissue for implantation into the human body or for in vitro drug testing is one of the challenging tasks facing tissue engineers. In the present study, we utilized a perfusion bioreactor system equipped with a novel flow-distributing mesh for online cell seeding into macroporous alginate scaffolds and cultivation of multiple constructs of the C3A human hepatocyte cell line. Optimization of the medium flow rate (100 mL/min) and perfusion duration (12 h) yielded cell constructs with high cell seeding efficiency (98% of the input cells) and cell distribution throughout the entire scaffold. Further, we show that interstitial medium flow enabled uniform cell delivery into 35 constructs lined across the bioreactor cross section. Perfusion-cultivated cell constructs revealed much greater rates of cell proliferation, albumin-specific secretion, and gene expression of the phase I enzyme, CYP3A4, and phase II enzyme, UGT2B7, than did static-cultivated constructs. Most impressive was the 50-fold increase in CYP3A4 expression of the perfused cell constructs as compared to the level in static-cultivated cell constructs. We thus believe that the hepatic tissue constructs developed herein may be used in drug discovery programs for elucidating drug metabolism and toxicity profiles and for treating failing livers.     

9-(2-膦酰甲氧乙基)腺嘌呤及其位置异构体3-(2-膦酰甲氧乙基)腺嘌呤的合成和抗病毒活性研究

Phosphonylmethoxyethyl)adenine (1),PMEA,an acyclic nucleotide withbroad-spectrum antiviral activity was synthesized with some modifications of Holy's procedure.Simutaneously,an N-3 regioisomer(2)of PMEA and a by-preduct, formaldehyde di-[2-(9-adenyl)ethyl] acetal(7)were seperated by silica gel chromatography in the ratio of 50:10:1.Compound(2)and(7) are new compounds that we have not yet found in literatures. The structure of them weredetermined with ¹HNMR,2DNMR, MS and Spot test.Antiviral test showed that N-3 isomer(2)completely lost activity against both HIV-1 and HSV-1 in vitro. It seems that regiospecificity of theacyclic nucleotide structure is important for antiviral activity.     

Heterotypic adherence between human B-lymphoblastic and pre-B- lymphoblastic cells and marrow stromal cells is a biphasic event: integrin very late antigen-4 alpha mediates only the early phase of the heterotypic adhesion

Heterotypic adherence between marrow stromal cells (MSC) and lymphoblastic cells is essential for normal lymphopoiesis and malignant lymphoblastic development. However, the detailed molecular mechanisms by which this heterotypic adherence occurs are poorly understood. The cell-cell interactions between a B-lymphoblastic cell line (UTMB-460) and a pre-B-cell line (NALM-6) with MSC were chosen as models to investigate potential mechanisms and adhesion molecules involved in the apposition between normal and malignant lymphoblastic cells and MSC. A parallel-flow detachment assay (PFDA) and a 51Cr detachment assay, coupled with monoclonal antibody (MoAb) blocking experiments, were used to quantify the attachment of lymphoblastic cells to confluent monolayers of MSC. The apposition between MSC and B-lymphoblastic cells (UTMB-460 cells) was investigated for variable time periods, ranging from 1 minute to 4 hours. Results from the temporal study suggest that the heterotypic adherence of the B-lymphoblastic cells to MSC is a biphasic event and the interactions occur rapidly (< or = 1 minute) after the two cells come into contact. More specifically, the early phase of adherence (< or = 15 minutes) solely involves very late antigen-4 alpha (VLA-4 alpha)/vascular cell adhesion molecule 1 (VCAM- 1) interactions, as evidenced by the nearly complete inhibition (93%) of UTMB-460 cell adherence in the presence of anti-VLA-4 alpha. The late phase (> or = 30 minutes) proceeds despite the continuous presence of anti-VLA-4 alpha. In addition, the late-phase adherence is not affected by MoAbs to LFA-1, CD44, VCAM-1, E-selectin, or L-selectin, which suggests the possible involvement of other adhesion molecules. Adherence of pre-B-lymphoblastic cells (NALM-6) to MSC is also biphasic. Integrin VLA-4 is again a major player in the early phase of pre-B-lymphoblastic cell/MSC interactions. The early phase of adherence may be important in homing of the malignant lymphoblastic cells to the MSC and the late phase in retention of malignant lymphoblastic cells in the bone marrow.