Quantification of vitamin C in the rat brain in vivo using short echo-time 1H MRS.

Both ultrashort echo-time STEAM and MEGA-PRESS-edited spectroscopy were used to validate noninvasive quantification of vitamin C (ascorbate) in the developing rat brain, where changes in ascorbate concentration have been reported. Despite strong overlap with resonances from glutamine, glutamate, glutathione, and macromolecules, reliable quantification of ascorbate (Cramer-Rao lower bounds<0.2 micromol/g) by LCModel analysis of STEAM (TE=2 ms) spectra was possible at 9.4 T. Ascorbate concentrations quantified from the STEAM spectra were in very good agreement with concentrations calculated from fully resolved ascorbate resonances in MEGA-PRESS-edited spectra measured from identical volumes of interest. Ascorbate concentrations measured using STEAM decreased with increasing postnatal rat age, in agreement with published brain ascorbate concentrations measured in vitro using high-performance liquid chromatography (HPLC).     

Hyperemic Islets: A Possible Explanation for Poor Yields in Human and Porcine Islet Isolation

When studying histological characteristics of human and porcine pancreata in relation to islet isolation, we encountered a remarkably high number of hyperemic islets. The abnormalities observed in these islets ranged from a single dilated vessel through multiple widely dilated vessels to hemorrhages extending into the surrounding exocrine tissue. We determined their possible relevance for outcomes of islet isolation. This study involved a histological examination of 143 porcine pancreata (72 juvenile and 71 adult) and islet isolation from 48 adult pancreata. Human pancreata obtained from 71 multiple organ donors yielded islet isolation in 24 cases. To determine their endocrine content, tissue samples were stained with Aldehyde Fuchsin. The presence of hyperemic islets was scored semiquantitatively with pancreata allotted to categories based on the severity. In humans and pigs we observed hyperemic islets in 48% of pancreata, but only 4.0 ± 2.4% of the islets were hyperemic. In both humans and pigs, significantly higher endocrine content was found in the most severely affected pancreata. When the higher endocrine content was taken into account and isolation results were expressed as ratios of yield and content, we observed significantly lower yields in the most affected pancreata in pigs with a trend toward lower yields in humans. A substantial proportion of human and porcine pancreata contain hyperemic islets. Although the results in humans are preliminary, our data suggest that this phenomenon may contribute to the unpredictable, highly variable islet yields in pigs and humans.     

应用低严格度—单引物聚合酶链反应对问号钩体中国参考株的…

Ｇ１、Ｇ２引物是对问号钩体具有特异性引物。分别用Ｇ１或Ｇ２单引物对问号钩体中国参考株进行前４个低严格度循环的ＰＣＲ扩增，扩增带谱显示赖型、犬型、致热型、秋季型、澳洲型、临海型、乌尔夫型、溶血型为一类，而爪哇型、拜伦型、波摩那型、七日热型、巴叶赞型塔拉索夫型、曼耗Ⅱ型是不与以上赖型等血清型本为一类，双曲钩体ａｔｏｃ型及伊利尼细丝体伊利尼型的扩增带谱与问号钩体截然不同。应用苯酚法提取的高纯度钩体ＤＮＡ     

Determination of the growth fraction in monoclonal gammopathy with the monoclonal antibody Ki-67

The monoclonal antibody Ki-67 reacts with a nuclear antigen that is present only in proliferating cells. The proportion of Ki-67 positive cells may therefore serve as a reliable measurement for the growth fraction in normal and neoplasmic cell populations. We have tested the significance of the MoAb Ki-67 in the classification of monoclonal gammopathy and compared the results with the plasma cell labelling index. In benign monoclonal gammopathy the percentage of Ki-67 positive plasma cells (median 1.6%) was significantly lower than in untreated multiple myeloma (median 9.6). Among the patients with more than 10% Ki-67 positive plasma cells there were some very short survivors. The largest growth fractions (median 41.8%) were found in patients with relapsing multiple myeloma indicating here a different growth pattern more resembling the high-grade lymphomas. A linear correlation between the proportion of Ki-67 positive plasma cells and the labelling index was not found. Determination of the plasma cell growth fraction with the monoclonal antibody Ki-67 in monoclonal gammopathy may help to discriminate benign monoclonal gammopathy from multiple myeloma and will probably identify a subgroup of multiple myeloma patients with a poor prognosis, including those with relapsing multiple myeloma.     

Increased tissue-type plasminogen activator activity in orthotopic but not heterotopic liver transplantation: the role of the anhepatic period.

The major cause of the increased tissue-type plasminogen activator activity during orthotopic liver transplantation is still unclear. Both the lack of hepatic clearance of tissue-type plasminogen activator in the anhepatic period and increased endothelial release from the graft on reperfusion have been proposed as the major causes. Heterotopic liver transplantation avoids the resection of the host liver and is a useful model to help differentiate between these two possibilities. In this study the fibrinolytic system was evaluated in 10 orthotopic liver transplantations, 18 heterotopic liver transplantations and a control group of 10 partial hepatic resections. A marked increment in tissue-type plasminogen activator activity, from 0.2 to 5.2 IU/ml (p less than 0.02), was observed during the anhepatic period of orthotopic liver transplantation, which rapidly normalized after reperfusion. In contrast, tissue-type plasminogen activator activity levels remained normal in heterotopic liver transplantation and partial hepatic resections. In orthotopic liver transplantation and in heterotopic liver transplantation no increase occurred in tissue-type plasminogen activator activity after reperfusion. The first venous hepatic outflow after reperfusion did not contain elevated tissue-type plasminogen activator activity levels. Plasma degradation products of fibrin and fibrinogen increased during the anhepatic period of orthotopic liver transplantation (from 2.60 to 8.80 micrograms/ml [p less than 0.008] and from 0.40 to 1.60 micrograms/ml [p less than 0.04], respectively) and remained elevated thereafter. In heterotopic liver transplantation and partial hepatic resections these levels remained low. In conclusion, the lack of hepatic clearance during the anhepatic period is probably the most important factor in the evolution of increased tissue-type plasminogen activator activity during orthotopic liver transplantation.     

A phase II study of sulofenur,a novel sulfonylurea,in recurrent epithelial ovarian cancer

Summary A total of 16 patients with recurrent epithelial ovarian cancer were treated with sulofenur (LY 186641), a novel oral sulfonylurea. All subjects had received previous chemotherapy. Anaemia occurred in all 16 patients, 14 of whom required a blood transfusion, and 2/16 patients received methylene blue for breathlessness due to methaemaglobinaemia. Treatment was discontinued in 2/16 cases due to rising liver enzyme values, which reverted to normal on cessation of the drug. There was no nausea or alopecia. Only two minor responses were seen. Plasma drug levels were insufficient to result in antitumour activity as extrapolated from animal data. Further studies that attempt to increase the bioavailability and improve the therapeutic index are warranted.     

Linkage of the MHC to familial multiple sclerosis suggests genetic heterogeneity. The Multiple Sclerosis Genetics Group

Multiple sclerosis (MS) is a demyelinating autoimmune disease of the central nervous system. While its etiology is not well understood, genetic factors are clearly involved. Until recently, most genetic studies in MS have been association studies using the case-control design testing specific candidate genes and studying only sporadic cases. The only consistently replicated finding has been an association with the HLA-DR2 allele within the major histocompatibility complex (MHC) on chromosome 6. Using the genetic linkage design, however, evidence for and against linkage of the MHC to MS has been found, fostering suggestions that sporadic and familial MS have different etiologies. Most recently, two of four genomic screens demonstrated linkage to the MHC, although specific allelic associations were not tested. Here, a dataset of 98 multiplex families was studied to test for an association to the HLA-DR2 allele in familial MS and to determine if genetic linkage to the MHC was due solely to such an association. Three highly polymorphic markers (HLA-DR, D6S273 and TNFbeta) in the MHC demonstrated strong genetic linkage (parametric lod scores of 4.60, 2.20 and 1.24, respectively) and a specific association with the HLA-DR2 allele was confirmed (TDT; P < 0.001). Stratifying the results by HLA-DR2 status showed that the linkage results were limited to families segregating HLA-DR2 alleles. These results demonstrate that genetic linkage to the MHC can be explained by the HLA-DR2 allelic association. They also indicate that sporadic and familial MS share a common genetic susceptibility. In addition, preliminary calculations suggest that the MHC explains between 17 and 62% of the genetic etiology of MS. This heterogeneity is also supported by the minority of families showing no linkage or association with loci within the MHC.