多发性骨髓瘤负性相关基因DAZAP2蛋白高效表达和纯化

目的在前期的研究中，DAZAP2基因在多发性骨髓瘤（Multiple myeloma，MM）患者中表达明显下调，可能为MM的负性基因．须进一步获得DAZAP2蛋白，制备抗体，从而在蛋白水平上研究DAZAP2的表达、结构和功能．方法将原核重组质粒pQE30－DAZAP2转化大肠杆菌，阳性菌株经1 mmol／LIPTG诱导表达目的蛋白，再经过纯化和透析结果IPTG诱导4hr时，得到大量重组目的蛋白，占可溶蛋白的20％左右，经过Ni—NTA层析柱纯化。获得分子量为17kD的DAZAP2蛋白浓度为0．97mg／m1．结论DAZAP2蛋白获得高效表达，并且建立快速简便的纯化方法，目的蛋白可以用于下一步的实验．     

骨髓浆细胞酸性磷酸酶积分用于多发性骨髓瘤病情的监测

对３６例多发性骨髓瘤（ＭＭ）患者骨髓涂片，行酸性磷酸酶（ＡＣＰ）染色。结果发现ＭＭ组的骨髓浆细胞ＡＣＰ积分明显高于对照组。ＭＭ组初诊时、缓解期和复发期４６人次检测结果表明，成ＭＭ病程中ＡＣＰ积分病情变化而变化，缓解期的较初诊时降低，复发期的又复增高。这种变化有时较骨髓浆细胞比例的变化与病情的关系更为密切，提示ＡＣＰ积分可作为ＭＭ病情监测的指标。     

Headaches and multiple sclerosis: a clinical study and review of the literature

Summary Whether multiple sclerosis (MS) can cause headaches is controversial. To clarify the association between headaches and MS we prospectively analyzed 104 consecutive MS patients using detailed headache evaluations. Fifty-four patients (52%) reported headaches, compared with 5 of 35 (14%) patients initially suspected to have MS but subsequently proven to have other disorders, and 18 of 100 (18%) matched general neurology patients. The MS patients had tension headaches or vascular headaches of the migraine type; there was no distinctive MS headache. Seven of these patients had headaches with their first MS symptoms, but in only one did headaches recur with disease activity. Headaches did not correlate with any clinical features of MS. We conclude that an association between headaches and MS may exist.     

Head injuries coexistent with pelvic or lower extremity fractures-early or delayed osteosynthesis

Summary The authors compared the results of a retrospective analysis of two groups of head-injured patients who had coexistent pelvic or lower extremit fractures. One group was treated with early osteosynthesis within the first 12 hours after trauma, simultaneously with neurosurgical treatment, while the second group was treated neurosurgically and osteosynthesis was postponed for 4 to 10 days. The second group revealed a higher mortality, which was due to fat embolism. We conclude that early osteosynthesis is the treatment of choice in patients with coexistent head injury and lower extremity fractures.     

Ethical issues in genetic screening for cancer

Genetically-based diseases with a late onset, such as BRCA1-dependent breast cancer or Huntington's disease, can be predicted by the screening of relevant mutations in members of high-risk families. Genetic screening is characterized by a conflict between respect for autonomy – e.g., the right not to know – and responsibility toward future generations (the duty to know for the sake of one's descendants). Other ethical conflicts are related to uncertainty as to benefits deriving from screening for mutations, since for most conditions no clearly effective therapeutical strategy has as yet been defined. In addition to monogenic high-penetrance conditions, polygenic low-penetrance susceptibility is attracting increasing attention, in particular with respect to environmental-genetic interactions (metabolic polymorphisms). A simple approach to genetic screening would be to weigh the benefits and costs of genetic screening against those of primary prevention, and a superficial conclusion might be that genetic screening is less expensive and, overall, more practicable than restriction of toxic exposures or other known risk factors for the disease. Economic advantage notwithstanding, however, giving precedence to screening over primary prevention would be unacceptable. A serious hazard of genetic screening is the implicit limitation of research efforts aimed at primary prevention, and a serious drawback is its potential application for selection of non-susceptible employees. The principle of equity is easily violated by genetic screening of workers in view of the fact that genetically-based metabolic polymorphisms are distributed unevenly among different ethnic groups.     

Iso-electric focusing of aqueous humour IgG in multiple sclerosis

Samples of aqueous fluid were obtained from 35 controls who were people undergoing routine cataract surgery. Similar samples were taken from seven patients with clinically definite multiple sclerosis (MS) and a previous history of optic neuritis, either at cataract surgery or as an elective procedure. Oligoclonal bands were found in only one subject who suffered from the MS-uveitis syndrome.     

Prolonged dynamic clinico-immunological observation of 85 patients with definite multiple sclerosis: First steps towards monitoring process activity

Prolonged clinico-immunological observation of 85 patients with definite multiple sclerosis (MS) was performed in order to elucidate the connections between the clinical and immune state. A battery of immunological investigations was performed, including estimation of T-cell subpopulations in blood and cerebrospinal fluid (CSF); proliferative responses of circulating lymphocytes to mitogens, recombinant interleukin-2 (rIL2) and myelin basic protein levels in different culture conditions; levels of immunoglobulin (Ig) in sera and CSF, and of Ig production in vitro; indices of IL2 synthesis and IL2 sensitivity; production of prostaglandin E2 and tumour necrosis factor (TNF) alpha by monocytes and levels of -endorphin in sera and supernatants phytohaemagglutinin of (PHA)-activated cells. Clinical observation was performed periodically using Kurtzke scales and was supplemented by repeated recording of evoked potentials and magnetic resonance imaging. Initial investigations showed specific differences between patients with MS and the control groups (donors and patients with other neurological disorders of the same age). Correlative and regressive analyses showed no association between immunological and clinical parameters at the initial investigation, although immunological indexes were inter-related, and indicated specific alterations in immuno-regulation in MS. Retrospective analysis revealed associations between the clinical status of patients with MS and their previous immune status. Evidence of cell activation — including a decreased percentage of circulating cells with differential antigens, lower cell mitogen-induced proliferative responses in vitro, with restoration following the addition of autoserum, greater IL2 sensitivity, and increased TNF-alpha production by macrophages — often predicted the clinical manifestation of deterioration. It is proposed that the immunopathological process in MS has a number of stages with characteristic features, and that progression from one stage to another can be subclinical. No single immunological index can be used to determine stage. Only systemic alterations reflect the real situation, whilst every patient has some abnormalities. A system of clinico-immunological monitoring could severe as the basis for a new approach to the dynamic treatment of MS.     

Percutaneous burrhole trephination of the skull: a study of 519 cases

We want to report on our experiences with the percutaneous trephination using a 2.35 mm round dental drill with serrated saws around it, a Rosenbohrer. It is a methodically similar activity as described by J. Zentner [11].From 1981 to 1992 519 patients were treated and 546 trephinations were performed.At the beginning this treatment was only used in connection with intracerebral bleedings and biopsies.In a considerable short time the indication could be extended to the subdural hematoma, tumor cyst, obstructive hydrocephalus as well as to the abscess and the subdural epyema.The rate of infection was 1.28% and the risk of bleeding 0.36%.In our opinion the advantages of this small electrical trephination are the easy handling, the universal use and mobility and the avoidable risk of anesthesia as well as the sterilisation at the same time and the stopping of blood, caused by the contact surface friction.     

Intrapulmonary gas mixing and dead space in artificially ventilated dogs

In this study we have investigated the effects of breath holding and of the physical properties of gases on four different respiratory dead spaces (V _D): the Fowler, the physiological, the washout and the inert gas dead space. The experiments were performed with dogs which were ventilated artifically with breathing patterns with different post-inspiratory breath holding times (t _a) of 0, 0.5, 1.0 and 2.0 s. Tracer amounts of acetone, ether and enflurane were infused continuously into a peripheral vein and a bolus of a mixture of krypton, Freon12 and SF₆ was introduced into the peritoneal cavity. After reaching steady state, samples of arterial blood, mixed venous blood and mixed expired air were taken simultaneously. From the partial pressures (P _a, P _¯V and P respectively) we determined the excretion (=P/P_¯V), retention (R=P_a/P_¯V) and the physiological dead space fraction (V _D,phys/V _T=(1 P/P_a) for each gas, where V _T is tidal volume. Further, we recorded the expirograms of the six tracer gases and of CO₂ from which the Fowler dead space fractions (V _D,Fowler/V _T) of the different gases were determined. Also the washout dead space fractions (V _D,washout/V _T) for He and SF₆ were determined as well as the inert gas dead space fraction (V _D,MIGET/V _T) with the use of the multiple inert gas elimination technique (MIGET).With the exception of V _D,phys/V _T for SF₆, all dead space fractions decreased with increasing t _a. V _D,phys/V _T for the poorly soluble gas SF₆ was considerably larger than V _D,phys/V _T for the remaining gases. For the highly soluble acetone V _Fowler/V _T was considerably smaller than V _D,Fowler/V _T for the other gases. V _{D,washout,SF6}/V _T was always larger than V _D,washout,He/V _T and V _D,Fowler,SF6/V _T. Further, V _D,phys/V _T was larger than V _D,Fowler/V _T for SF₆ and acetone. However, for gases with intermediate solubility in blood V _D,phys/V _T tended to be smaller than V _D,Fowler/V _T. We conclude that the respiratory dead spaces are affected by the breathing pattern and by the physical properties of gases, i.e. their diffusivity in alveolar gas and their solubility in blood or lung tissue.     

Long-term therapy with recombinant human erythropoietin (rHu-EPO) in progressing multiple myeloma

Recombinant human erythropoietin (rHu-EPO) is an effective growth factor for erythroid progenitor cells in anemia provoked by several conditions, including bone marrow tumors such as multiple myeloma (MM). We studied a group of 54 patients with MM undergoing second-induction chemotherapy. Thirty of them were randomly assigned to receive rHu-EPO at an initial dosage of 150 units/kg body weight three times a week, increased to 300 units/kg from the sixth week to the end of the 24-week study. Hemoglobin (Hb) levels increased in 77.7% of these patients by the eighth week. In addition, five transfusion-dependent patients in treatment with the VMCP protocol completed the trial without requiring blood supplement after the third month, whereas seven control patients required frequent supplements. Monthly assessment of hematologic parameters demonstrated the ability of rHu-EPO to increase reticulocyte counts, whereas five patients became resistant to the second-induction chemotherapy in apparent concurrence with their rHu-EPO therapy. The response to rHu-EPO in four of the five MM patients receiving cytotoxic protocols combined with -interferon (-IFN) included an increase of serum IgM after the third month. This effect was not demonstrable in any other group, including three rHu-EPO-untreated patients undergoing -IFN + VMCP combined therapy, as well as rHu-EPO-treated patients not receiving a-IFN. Our data suggest that -IFN plus rHu-EPO treatment in MM patients is effective in restoring normal B cell function. These results may reflect in vivo the modulation of normal human B cells and lymphoblasts by rHu-EPO observed in vitro.