缺陷腺病毒载体表达重复10次的Aβ3-10基因疫苗鼻黏膜免疫APPswe, PSEN1dE9转基因小鼠可诱导出Th2型免疫反应

Immunotherapy for Alzheimer’s disease (AD) is effective in improving cognitive function in transgenic mouse models of AD. Because the AN1792 [beta-amyloid (Aβ) 1-42] vaccine was halted because of T cell mediated meningoencephalitis, many scientists are searching for a novel vaccine to avoid the T cell mediated immune response caused by the Aβ1-42. Importantly, the time when the immunization is begun can influence the immune effect. In this study, an adenovirus vaccine was constructed containing 10 × Aβ3-10 repeats and gene adjuvant CpG DNA. Transgenic AD mice were immunized intranasally for 3 months. After 10 × Aβ3-10 vaccine immunization, high titers of anti-Aβ42 IgG1 predominant antibodies were induced. In spatial learning ability and probe tests, the 10 × Aβ3-10 immunized mice showed significantly improved memories compared to control mice. The 10 × Aβ3-10 vaccine resulted in a robust Th2 dominant humoral immune response and reduced learning deficits in AD mice. In addition, the 10 × Aβ3-10 vaccine might be more efficient if administered before Aβ aggregation at an early stage in the AD mouse brain. Thus, the adenovirus vector encoding 10 × Aβ3-10 is a promising vaccine for AD.     

Adoptive immunotherapy evaluating escalating doses of donor leukocytes for relapse of chronic myeloid leukemia after bone marrow transplantation: separation of graft-versus-leukemia responses from graft-versus-host disease

Infusions of large numbers (> 10(8)/kg) of donor leukocytes can induce remissions in patients with chronic myeloid leukemia (CML) who relapse after marrow transplantation. We wanted to determine if substantially lower numbers of donor leukocytes could induce remissions and, if so, whether this would reduce the 90% incidence of graft-versus-host disease (GVHD) associated with this therapy. Twenty-two patients with relapsed CML were studied: 2 in molecular relapse, 6 in cytogenetic relapse, 10 in chronic phase, and 4 in accelerated phase. Each patient received escalating doses of donor leukocytes at 4- to 33-week intervals. Leukocyte doses were calculated as T cells per kilogram of recipient weight. There were 8 dose levels between 1 x 10(5) and 5 x 10(8). Lineage-specific chimerism and residual leukemia detection were assessed using sensitive polymerase chain reaction (PCR) methodologies. Nineteen of the 22 patients achieved remission. Remissions were achieved at the following T-cell doses: 1 x 10(7) (n = 8), 5 x 10(7) (n = 4), 1 x 10(8) (n = 3), and 5 x 10(8) (n = 4). To date, 15 of the 17 evaluable patients have become BCR-ABL negative by PCR. The incidence of GVHD was correlated with the dose of T cells administered. Only 1 of the 8 patients who achieved remission at a T-cell dose of 1 x 10(7)/kg developed GVHD, whereas this complication developed in 8 of the 11 responders who received a T-cell dose of > or = 5 x 10(7)/kg. Three patients died in remission, 1 secondary to marrow aplasia, 1 of respiratory failure and 1 of complications of chronic GVHD. Sixteen patients who were mixed T-cell chimeras before treatment became full donor T-cell chimeras at the time of remission. Donor leukocytes with a T-cell content as low as 1 x 10(7)/kg can result in complete donor chimerism together with a potent graft-versus-leukemia (GVL) effect. The dose of donor leukocytes or T cells used may be important in determining both the GVL response and the incidence of GVHD. In many patients, this potent GVL effect can occur in the absence of clinical GVHD.     

基于1H-NMR代谢组学的阿胶化学成分差异性分析方法初探

目的 采用氢核磁共振(¹H-NMR)代谢组学技术对不同生产厂家的阿胶酸水解成分进行差异性比较。方法 对5个不同生产厂家的阿胶进行酸水解,然后进行¹H-NMR分析。对所得的¹H-NMR图谱进行化学成分归属指认,并结合相关软件进行多元统计分析,找出差异性化学成分。结果 从阿胶¹H-NMR谱中指认出17种化学成分;通过对A、C、D、E厂家生产的阿胶与B厂家生产的阿胶进行比较分析,找出了相应的差异性成分,主要包括异亮氨酸、羟脯氨酸、精氨酸、亮氨酸、苯丙氨酸、缬氨酸、赖氨酸和乙酰丙酸等。结论 ¹H-NMR代谢组学方法可用于不同厂家阿胶化学成分差异性的分析,为阿胶的质量控制提供新方法和新思路。     

Protein Losing Enteropathy in Severe Atopic Dermatitis in an Exclusively Breast-Fed Infant

Abstract:   We first report a case of protein losing enteropathy in severe atopic dermatitis in an exclusively breast-fed 5-month-old infant. Protein losing enteropathy was confirmed by fecal α₁-antitrypsin clearance test and imaged successfully by ^99mTc-human serum albumin scintigraphy. The present case highlights that protein losing enteropathy in severe infantile atopic dermatitis is being a topic of concern and also an issue even in exclusive breast feeding patients.     

Paediatric rehabilitation in a developing country—India in relation to aetiology,consequences and outcome in a group of 459 burnt children

Age, aetiology of burn, percentage body surface area burnt and post-burn sequelae have a direct relationship to the rehabilitative necessity in burnt children in a developing country—India. In spite of the gross disfigurements and sequelae, only adolescent children required psychosocial rehabilitation. These are the results following a retrospective analysis of 459 paediatric burn patients in Madras, India.     

Organ culture stability of the intervertebral disc: Rat versus rabbit

There is a need to develop mechanically active culture systems to better understand the role of mechanical stresses in intervertebral disc (IVD) degeneration. Motion segment cultures that preserve the native IVD structure and adjacent vertebral bodies are preferred as model systems, but rapid ex vivo tissue degeneration limits their usefulness. The stability of rat and rabbit IVDs is of particular interest, as their small size makes them otherwise suitable for motion segment culture. The goal of this study was to determine if there are substantial differences in the susceptibility of rat and rabbit IVDs to culture‐induced degeneration. Lumbar IVD motion segments were harvested from young adult male Sprague–Dawley rats and New Zealand White rabbits and cultured under standard conditions for 14 days. Biochemical assays and safranin‐O histology showed that while glycosaminoglycan (GAG) loss was minimal in rabbit IVDs, it was progressive and severe in rat IVDs. In the rat IVD, GAG loss was concomitant with the loss of notochordal cells and the migration of endplate (EP) cells into the nucleus pulposus (NP). None of these changes were evident in the rabbit IVDs. Compared to rabbit IVDs, rat IVDs also showed increased matrix metalloproteinase‐3 (MMP‐3) and sharply decreased collagen type I and II collagen expression. Together these data indicated that the rabbit IVD was dramatically more stable than the rat IVD, which showed culture‐related degenerative changes. Based on these findings we conclude that the rabbit motion segments are a superior model for mechanobiologic studies. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 838–846, 2013     

Long-term nasogastric tube feeding in elderly stroke patients — an assessment of nutritional adequacy and attitudes to gastrostomy feeding in asians

Background

Gastrostomy feeding is superior to long-term nasogastric (NG) feeding in patients with dysphagic stroke, but this practice remains uncommon in Asia. We sought to examine the nutritional adequacy of patients on long term NG feeding and identify barriers to gastrostomy feeding in these patients.

Methodology

A prospective comparison of Subjective Global Assessment (SGA), and anthropometry (mid-arm muscle circumference, MAMC; triceps skinfold thickness, TST) between elderly stroke patients on long-term NG feeding and matched controls was performed. Selected clinicians and carers of patients were interviewed to assess their knowledge and attitudes to gastrostomy feeding.

Results

140 patients (70 NG, 70 oral) were recruited between September 2010 and February 2011. Nutritional status was poorer in the NG compared to the oral group (SGA grade C 38.6% NG vs 0% oral, p<0.001; TST males 10.7 + 3.7 mm NG vs 15.4 + 4.6 mm oral, p<0.001; MAMCmales 187.9 + 40.4 mm NG vs 228.7 + 31.8 mm oral, p<0.001). 45 (64.3%) patients on long-term NG feeding reported complications, mainly consisting of dislodgement (50.5%), aspiration of feed content (8.6%) and trauma from insertion (4.3%). Among 20 clinicians from relevant speciliaties who were interviewed, only 11 (55%) clinicians would routinely recommend a PEG. All neurologists (100%) would recommend a PEG, whilst the response was mixed among non-neurologists. Among carers, lack of information (47.1%) was the commonest reason stated for not choosing a PEG.

Conclusion

Elderly patients with stroke on long term NG feeding have a poor nutritional status. Lack of recommendation by clinicians appears to be a major barrier to PEG feeding in these patients.     

Lack of mGluR6‐related cascade elements leads to retrograde trans‐synaptic effects on rod photoreceptor synapses via matrix‐associated proteins

Heterotrimeric G‐proteins couple metabotropic receptors to downstream effectors. In retinal ON bipolar cells, G_o couples the metabotropic receptor mGluR6 to the TRPM1 channel and closes it in the dark, thus hyperpolarizing the cell. Light, via GTPase‐activating proteins, deactivates G_o, opens TRPM1 and depolarizes the cell. G_o comprises Gα_o1, Gβ3 and Gγ13; all are necessary for efficient coupling. In addition, Gβ3 contributes to trafficking of certain cascade proteins and to maintaining the synaptic structure. The goal of this study was to determine the role of Gα_o1 in maintaining the cascade and synaptic integrity. Using mice lacking Gα_o1, we quantified the immunostaining of certain mGluR6‐related components. Deleting Gα_o1 greatly reduced staining for Gβ3, Gγ13, Gβ5, RGS11, RGS7 and R9AP. Deletion of Gα_o1 did not affect mGluR6, TRPM1 or PCP2. In addition, deleting Gα_o1 reduced the number of rod bipolar dendrites that invaginate the rod terminal, similar to the effect seen in the absence of mGluR6, Gβ3 or the matrix‐associated proteins, pikachurin, dystroglycan and dystrophin, which are localized presynaptically to the rod bipolar cell. We therefore tested mice lacking mGluR6, Gα_o1 and Gβ3 for expression of these matrix‐associated proteins. In all three genotypes, staining intensity for these proteins was lower than in wild type, suggesting a retrograde trans‐synaptic effect. We propose that the mGluR6 macromolecular complex is connected to the presynaptic rod terminal via a protein chain that includes the matrix‐associated proteins. When a component of the macromolecular chain is missing, the chain may fall apart and loosen the dendritic tip adherence within the invagination.