Vitamin B-6 metabolism in the brains of young adult and senescent mice

The steady state levels of pyridoxal-P and pyridoxamine-P, the activities of pyridoxal (pyridoxine) kinase and pyridoxamine-(pyridoxine)-P oxidase, and the metabolism of [³H]pyridoxine were determined in the brains of C57B1/6J mice of selected ages. The steady state concentratioons of the coenzymes and the activities of the enzymes required for pyridoxal-P synthesis did not change significantly as a function of age. The uptake and metabolism of vitamin B-6 by the brain was studied by injecting [³H]pyridoxine in the tail vein of young adult and senescent mice, killing the mice after 15 or 30 min, and separating the B-6 metabolites by ion exchange chromatography. More total radioactivity was accumulated in 15 min in the brains of the senescent mice than the brains of the young mice. The brains from both age groups rapidly synthesized pyridoxal-P from pyridoxine. However, less radioactive pyridoxamine-P and more radioactive pyridoxal were formed in the brains of the senescent mice than in the young mice killed 15 min after injection. These results are similar to those obtained for the metabolim of [³H]-pyridoxine in the liver of these senescent mice. The senescent mice appear to be vitamin B-6 deficient, have decreased brain amino acid transaminase activity, and either increased pyridoxal-P phosphatase activity or decreased protection of brain pyridoxal-P.     

A novel<Emphasis Type="Italic"> PMP22</Emphasis> mutation Ser22Phe in a family with hereditary neuropathy with liability to pressure palsies and CMT1A phenotypes

We describe a Cypriot family in which some family members presented with episodes of pressure palsies, while other family members had a slowly progressive chronic polyneuropathy typical of the Charcot-Marie-Tooth type 1 phenotype. All family members were evaluated clinically, with nerve conduction studies, and with genetic testing. In all affected individuals there was clinical and electrophysiological evidence of diffuse demyelinating sensorimotor polyneuropathy and a novel point mutation in the PMP22 gene (Ser22Phe) was identified.     

Behavioural profiling of a murine Charcot-Marie-Tooth disease type 1A model

Different features of motor behaviour were studied on a transgenic mouse model of Charcot-Marie-Tooth's disease (CMT). Mutants with 4 or 7 copies of the human PMP22 gene leading to a phenotype significantly close to CMT's disease type 1A were compared with control animals. The aim of the study was to validate this transgenic model and to characterise the impairments occurring in the various lines. Three main types of analysis were performed in 2-month-old mice without any peculiar visible deficit: (i) a study of standardised clinical tests (SHIRPA protocol) demonstrated that only a few motor deficits were expressed; (ii) a measurement of general spontaneous activity by means of a commercial video-tracking system was performed and revealed that the main spontaneous activities were identical in the three lines with, however, some slight localised modifications; and, (iii) by contrast, the three lines respond very differently to the footprints, grip strength, splay test and rotarod test. Even in lines with a significantly limited copy number of the transgene, we observed and quantified impairments. In conclusion, mutants of CMT1A seem to be a very pertinent model of this human pathology and will certainly be useful for therapeutic procedures and for theoretical studies on this disease.     

除害专业队伍实施城市灭蚊的研究

目的比较3个在用人、培训、技术措施和管理方面不同的实施单位在城市灭蚊工作中灭蚊效果的差异。方法2002年6~9月,3个实施单位分别承包了武汉7个灭蚊区的灭蚊试点工作。其中城区灭蚊项目组将其负责的灭蚊区内下岗人员训练为除害员,开展了蚊虫孳生地普查,然后利用普查资料和地图搜索、处理蚊虫孳生地。除害员对灭蚊区市民进行面对面的灭蚊宣传。项目组建立防止遗漏蚊虫孳生地的管理制度。而另外两个实施单位在这几方面与项目组不同。试点结束前由专家对灭蚊区进行问卷调查和达标考核。结果在项目组负责的灭蚊区有12个蚊密度测试点,其中10个点的RPI值为0。普查后每小时能在灭蚊区找到的蚊虫孳生地数量显著下降。项目组的问卷调查和达标考核结果均优于另外2个实施单位。结论蚊虫孳生地普查,训练灭蚊区当地的下岗人员为除害员,建立合理的管理制度能有效防止蚊虫孳生地的遗漏,提高除害专业队伍实施城市灭蚊的工作质量。     

Vitamin B-6 metabolism in the livers of young adult and senescent mice

The steady state level of pyridoxal-P and the activities of pyridoxal (pyridoxine) kinase and pyridoxine-P oxidase were determined in the livers of C57B1/6J mice of selected ages. The concentration of pyridoxal-P and the activities of these two enzymes did not change significantly as a function of age. In addition, the uptake and metabolism in the liver of [³H]pyridoxine injected in the tail vein of young adult and senescent mice was studied. More total radioactivity was accumulated in 15 and 30 min in the livers of the senescent mice than the livers of the young mice. The livers from both age groups rapidly synthesized the coenzyme, pyridoxal-P, from pyridoxine. However, a smaller percentage of the total radioactivity appeared in the other coenzyme form, pyridoxamine-P, and a larger percentage appeared in the hydrolysis product, pyridoxal, in the livers of the senescent mice than the livers of the young mice. These results may indicate that the senescent mice were B-6 deficient, that they had decreased total amino acid transaminase activity, and that they had increased pyridoxal-P phosphatase activity or decreased protection of liver pyridoxal-P.     

Glucocorticosteroids stimulate the activity of the promoters of peripheral myelin protein-22 and protein zero genes in Schwann cells

To better understand the mechanism by which glucocorticosteroids (GLUC) could enhance myelination in the PNS, cultured rat Schwann cells were transiently transfected with reporter constructs in which luciferase expression was controlled by the promoter region of either the peripheral myelin protein-22 (PMP22) or the protein zero (P(0)) genes. GLUC stimulated the activity of the P(0) promoter and the PMP22 promoters 1 and 2. The effect of GLUC was specific as estradiol and testosterone did not activate the promoters. The antagonist RU486 did not abolish the effect of GLUC, but instead stimulated promoter activities by itself. In the mammary carcinoma cell line 34i, which expresses GLUC receptors, GLUC did not stimulate the P(0) and PMP22 promoters while the promoter of the mouse mammary tumor virus was strongly activated. Thus, the activation by GLUC of the promoter activities of two peripheral myelin protein genes is Schwann cell-specific.     

不同浓度血小板激活剂激活血小板微粒膜表达PAC-1、CD62p的比较

目的　比较不同浓度的激活剂激活血小板形成的血小板微粒 (PMP)膜表达PAC 1、CD6 2p的差异。方法　抽取 10例健康人静脉血 ,以枸橼酸钠抗凝 ,离心得富血小板血浆 ,分别以不同浓度的ADP(5、10、2 0 μmol/L)、凝血酶 (0 .1、0 .5、1.0U/ml)、胶原 (5、10、2 0 μg/ml)作诱导剂 ,激活同一标本中的血小板 ,比较其PMP表达PAC 1和CD6 2p的情况。 结果　随着激活剂浓度的增加 ,CD6 2p PMP、PAC 1 PMP的百分率都逐渐增加 ,同一诱导剂各浓度间有显著性差异 (P <0 .0 1)。结论　不同刺激强度的血小板诱导剂ADP、凝血酶、胶原 ,随浓度的增加 ,其诱导血小板所形成的CD6 2p PMP、PAC 1 PMP的百分率逐渐增加。     

Peritoneal dissemination from high-grade appendiceal cancer treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC)

Background

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have shown variability in survival outcomes when used to treat peritoneal surface disease (PSD) from appendiceal and colorectal cancers. The primary goal of this study was to examine outcomes for high-grade appendiceal (HGA) and high-grade colonic primaries after CRS-HIPEC to determine if a significant difference exists between the two groups.

Methods

A retrospective analysis of patients with peritoneal dissemination from appendiceal and colonic primaries were identified in a prospectively maintained database of 1,223 CRS-HIPEC procedures performed between 1991 and 2015. Patient demographics, performance status resection status, tumor grade, nodal status, morbidity, mortality, and survival were reviewed with biopsy-proven PSD being classified according to primary site. Univariate and multivariate analyses were performed, and outcomes compared.

Results

The study identified 171 CRS-HIPEC procedures for 165 patients: 110 (66.7%) for HGA and 55 (33.3%) for high-grade colonic lesions. Observed median disease-free survival (DFS) and overall survival (OS) for both groups were the same at14.4 and 18 months, respectively. Median survival according to resection status for R0/R1, R2a, and R2b/c were 36, 15.6, and 8.4 months (P<0.0001). Median OS for those who received preoperative chemotherapy versus those who did not were 14.4 and 20.4 months, respectively (P=0.01). For those who received preoperative chemotherapy, no difference was apparent in the DFS interval (P=0.34). Multivariate predictors of OS included resection status (P<0.0001) and lymph node involvement (P=0.0005).

Conclusions

Preoperative chemotherapy offered no clear DFS or OS benefit, for HGA or high-grade colon cancer patients. Complete cytoreduction offered the greatest survival benefit to both groups with a correlating drop in survival to resection status. Outcomes for high grade appendiceal cancer are remarkably similar to colon cancer.     

Systemic lupus erythematosus and systemic sclerosis: All roads lead to platelets

Systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) are two phenotypically distincts inflammatory systemic diseases. However, SLE and SSc share pathogenic features such as interferon signature, loss of tolerance against self-nuclear antigens and increased tissue damage such as fibrosis. Recently, platelets have emerged as a major actor in immunity including auto-immune diseases. Both SLE and SSc are characterized by strong platelet system activation, which is likely to be both the witness and culprit in their pathogenesis. Platelet activation pathways are multiple and sometimes redundant. They include immune complexes, Toll-like receptors activation, antiphospholipid antibodies and ischemia-reperfusion associated with Raynaud phenomenon. Once activated, platelet promote immune dysregulation by priming interferon production by immune cells, providing CD40L supporting B lymphocyte functions and providing a source of autoantigens. Platelets are actively implicated in SLE and SSc end-organ damage such as cardiovascular and renal disease and in the promotion of tissue fibrosis. Finally, after understanding the main pathogenic implications of platelet activation in both diseases, we discuss potential therapeutics targeting platelets.     

Dejerine-Sottas neuropathy in mother and son with same point mutation of PMP22 gene

We studied a 25-year-old black woman with healthy parents and her 2-year, 11-month-old son. Her motor development was delayed and she started to walk with support when she was 6 years old. She never walked independently and had always used a wheelchair. Neurological evaluation showed severe weakness and atrophy of her feet, legs, and hands, bilateral pes cavus and hammertoes, corrected scoliosis, hypesthesia for proprioception and vibration sense in both feet and ankles, and areflexia. She had normal intelligence. Her son also had delayed motor milestones and was still unable to stand and walk independently at almost 3 years. Neurological evaluation revealed diffuse muscle hypotonia and weakness with generalized areflexia and normal intelligence. No muscle atrophies or feet deformities were noticed. Nerve conduction velocities showed significant slowing (less than 5 m/s) with prolonged distal latencies (above 30 ms). Compound motor action potential amplitudes were markedly reduced. Electromyography revealed polyphasic motor unit potentials. Molecular genetic studies indicated a Trembler type missense point mutation of exon 4 of the peripheral myelin protein 22 gene that led to the substitution of a spartic acid for glycine in both the mother and her son. Her parents showed normal DNA studies. © 1997 John Wiley & Sons, Inc.