Treatment of schizophrenic psychoses with Lyorodin

Forty-four patients suffering from acute and chronic schizophrenic psychoses were used to obtain, by using Lorr's scale (IMPS) and taking the changes in disease state observed within three months as a base, suggestions or pointers as to the proper treatment of disease with fluphenazine (lyorodin) which is a neuroleptically highly potent phenothiazine derivative. Megalomania, grandiose delusions apathetic and depressive syndromes showed marked tendencies toward major improvement. An "antiautistic" effect was observed in chronic patients. The effective dose was between 6 and 12 mg a day. The drug was well tolerated. In the majority of cases it was also necessary for antiparkinsonian drugs to be administered to patients. After twelve months of treatment, slight to major improvements or even freedom from symptoms could be observed in 28 cases (or 64%).     

A logic-based approach to rule induction in expert systems

Rule induction is an important part of learning in expert systems. Rules can help managers make more effective decisions and gain insight into the relationships between decision variables. We present a logic-based approach to rule induction in expert systems which is simple, robust and consistent. We also derive bounds on levels of certainty for combining rules. We apply our approach to the development of rules for the entry decisions of new products. We then discuss how the logic-based approach of rule induction can be used to create a decision support system and the methodology to create such a system.     

外延SCNN电光薄膜生长及研究

用激光脉冲沉积(PLD)法在MgO(001)衬底上成功地生长、制备出了外延铌酸锶钡钠(SCNN)电光薄膜.对生长制备出的SCNN电光薄膜用X射线衍射对其微观结构进行了测量研究;X射线衍射结果显示生长在MgO(001)衬底上的SCNN电光薄膜是外延膜;对生长在MgO(001)衬底上的外延SCNN电光薄膜在200～900nm光谱范围的透射光谱进行了测量研究,通过对薄膜透射光谱的振荡曲线分析计算得到了SCNN电光薄膜的光学常数,结果发现外延SCNN电光薄膜的折射率符合单电子模型.     

Molecular genetics of rust resistance in poplars (Melampsora larici-populina Kleb/Populus sp.) by bulked segregant analysis in a 2 x 2 factorial mating design

With random amplified polymorphic DNA (RAPD) markers, we have tagged a genomic region in Populus sp. involved in qualitative resistance to Melampsora larici-populina. Our approach was based on three steps: use of RAPD markers that can be quickly and efficiently researched: application of "bulked segregant analysis" technique on individuals of one interspecific family P. trichocarpa x P. deltoides to search for RAPD markers linked to resistance; and validation of these markers in two other families linked with the first one in a 2 x 2 factorial mating design. Of five detected markers, only one marker M03/04_480 was polymorphic in the three segregating families, involving 89 individuals and four different parents. We have estimated the recombination value of 1 cM with 1 cM sampling error.     

Evaluation of nefazodone as a serotonin uptake inhibitor and a serotonin antagonist in vivo

Nefazodone (2-[3-[4-(3-chlorophenyl)-1-piperazinyl]propyl]-5-ethyl- 2,4-dihydro-4-(2-phenoxyethyl)-3H-1,2,4-triazol-3-one) has been reported to be effective in the treatment of depression. Antagonism of serotonin type 2A (5HT2A) receptors, as well as inhibition of the serotonin (5HT) uptake carrier, has been suggested to contribute to the antidepressant action of nefazodone in vivo (Eison et al., 1990). Nefazodone weakly antagonized the quipazine-induced rise in rat serum corticosterone levels and the quipazine-induced increase in rat hypothalamic 3-methoxy-4-hydroxy-phenylglycol sulfate, suggesting blockade of 5HT2A receptors in vivo. Nefazodone, however, failed to antagonize the p-chloroamphetamine-induced depletion of mouse or rat brain 5HT, displaying a lack of effect on the 5HT uptake carrier. These data extend previous in vitro and in vivo data (Eison, et al. 1990) reporting nefazodone to be an antagonist at 5HT2A receptors, but fail to show inhibition of the 5HT uptake carrier in the same dose range.     

Maturation of peroxisomes in differentiating human hepatoblastoma cells (HepG2): possible involvement of the peroxisome proliferator-activated receptor alpha (PPAR alpha)

Although several variant alleles at the human NAT1 gene locus have been reported, their relationship to phenotypic variations in NAT1 function remains unclear. We have used in-vivo and invitro phenotyping tests, along with PCR-based cloning and heterologous expression, to investigate the extent of variation in NAT1 function and to characterize novel allelic variants at the NAT1 gene locus. The NAT1-selective substrate p-aminosalicylic acid (PAS) was used as a probe for NAT1 function. In-vivo PAS acetylation rates were estimated by determining the ratio of PAS to N-acetylated PAS (AcPAS) in urine and plasma following the oral ingestion of Nemasol Sodium. Excluding outliers, a 65-fold variation in the urinary AcPAS:PAS ratio was observed (n = 144), while a 5.6-fold variation in the plasma AcPAS:PAS ratio was seen in a subset (n = 19) of this sample. Urinary and plasma ratios correlated moderately (r = 0.74, p < 0.0005). One individual (case 244) had a marked impairment of PAS N-acetylation, with 10-fold lower urinary and plasma AcPAS:PAS ratios compared with other subjects. Biochemical investigations in whole blood lysates from case 244 suggested a NAT1 kinetic defect, with a 20-fold increased apparent K(m) for PAS and a 90-fold decreased Vmax for AcPAS formation. We subcloned, sequenced and expressed the protein-coding regions of the NAT1 alleles from case 244 and from seven other selected probands. Sequence analysis revealed the presence of two new variant alleles, designated as NAT1 x 14 and NAT1 x 15, in case 244, as well as one variant, NAT1 x 11, which has been observed in previous investigations. NAT1 x 14 contained a missense mutation (G560-->A) that is predicted to change a single amino acid (Arg187-->Gln), as well as two 3' non-coding region mutations (T1088-->A and C1095-->A) that have previously been observed in the NAT1 x 10 allelic variant. NAT1 x 15 had a single nonsense mutation (C559-->T; Arg187-->stop) and, thus, encodes a truncated protein. The activity of recombinant NAT1 14 mirrored the defective enzyme function in whole blood lysates from case 244, while NAT1 15 was completely inactive. Expressed NAT1 11, on the other hand, had identical activity to the wild type NAT1 4 allele, suggesting that the coding region mutations in this variant are functionally silent. The frequencies of NAT1 x 11, NAT1 x 14 and NAT1 x 15 were 0.021, 0.028 and 0.014 (n = 288 alleles), respectively, suggesting that they are relatively rare in our predominantly Caucasian sample.     

A computer-controlled spraying-freezing apparatus for millisecond time-resolution electron cryomicroscopy

The application of gene therapy techniques to the clinical problem of coronary restenosis has generated tremendous attention and enthusiasm. Use of gene transfer technology to prevent a common intractable illness would represent a watershed event for human gene therapy. However, the time is not yet right to initiate gene therapy trials for restenosis. The biology of restenosis is incompletely understood, catheter-based gene delivery is poorly adapted to the coronary circulation, and current gene transfer vectors are ill-suited for safe and effective gene delivery to the coronary artery wall. Basic research designed to overcome these obstacles is currently more appropriate than the initiation of clinical trials.     

Essential contribution of caspase 3/CPP32 to apoptosis and its associated nuclear changes

Caspases are fundamental components of the mammalian apoptotic machinery, but the precise contribution of individual caspases is controversial. CPP32 (caspase 3) is a prototypical caspase that becomes activated during apoptosis. In this study, we took a comprehensive approach to examining the role of CPP32 in apoptosis using mice, embryonic stem (ES) cells, and mouse embryonic fibroblasts (MEFs) deficient for CPP32. CPP32(ex3-/-) mice have reduced viability and, consistent with an earlier report, display defective neuronal apoptosis and neurological defects. Inactivation of CPP32 dramatically reduces apoptosis in diverse settings, including activation-induced cell death (AICD) of peripheral T cells, as well as chemotherapy-induced apoptosis of oncogenically transformed CPP32(-/-) MEFs. As well, the requirement for CPP32 can be remarkably stimulus-dependent: In ES cells, CPP32 is necessary for efficient apoptosis following UV- but not gamma-irradiation. Conversely, the same stimulus can show a tissue-specific dependence on CPP32: Hence, TNFalpha treatment induces normal levels of apoptosis in CPP32 deficient thymocytes, but defective apoptosis in oncogenically transformed MEFs. Finally, in some settings, CPP32 is required for certain apoptotic events but not others: Select CPP32(ex3-/-) cell types undergoing cell death are incapable of chromatin condensation and DNA degradation, but display other hallmarks of apoptosis. Together, these results indicate that CPP32 is an essential component in apoptotic events that is remarkably system- and stimulus-dependent. Consequently, drugs that inhibit CPP32 may preferentially disrupt specific forms of cell death.