N-甲基(3,4-亚甲二氧基苯甲酰)甲基-乙酰胺(SY-640)对化学致癌剂苯并芘与小鼠肝细胞核DNA共价结合的抑制作用

用小鼠肝细胞核制备和肝微粒体制备,研究了化合物SY-640对致癌剂苯并芘(BP)损伤肝细胞核的保护作用及与P-450的关系。结果表明,SY-640可显著抑制³H-BP与小鼠肝细胞核的DNA共价结合。SY-640连续po 3 d,可显著诱导小鼠肝微粒体细胞色素P-450含量及氨基比林脱甲基酶活性;给药1次2h内却只抑制氨基比林脱甲基酶活性。体外温孵实验表明,SY-640对小鼠肝微粒体氨基比林脱甲基酶活性也具有明显的抑制作用。差示光谱分析表明,SY-640可与细胞色素P-450形成络合物。提示该化合物对肝微粒体细胞色素P-450酶系的影响与其对化学致癌剂BP所致肝细胞毒性的保护作用有关。     

Cross-correlation between stress, pain, physical activity, and temporalis muscle EMG in tension-type headache

Thirty-six tension-type headache subjects and 36 non-headache matched controls recorded their temporalis muscle electromyographic (EMG) activity and their pain intensity, stress and physical activity levels in a daily diary. Measurements were performed every 30 min for 6 days (EMG 3 days only). A time-lagged cross-correlational analysis between pain, stress, physical activity, and EMG shows that the highest correlation coefficient values occurred between pain and stress at the same ( r =0.33) and at the two preceding 0.5 h time points ( r =0.21 and r =0.26) in the headache group. Virtually no correlation was found between pain, stress, or physical activity with EMG for either group. These data show that temporalis muscle activity levels were not related to the rise and fall of the subjects' pain or stress levels. Conversely, elevated stress appeared to be highly related to pain; it occurs as both an antecedent and simultaneous event with elevated headache pain.     

Molecular and biochemical analysis of protective protein/cathepsin A mutations: correlation with clinical severity in galactosialidosis [published erratum appears in Hum Mol Genet 1997 Jan;6(1):146]

Mutations in the gene encoding lysosomal protective protein/cathepsin A (PPCA) are the cause of the lysosomal disorder galactosialidosis (GS). Depending on age of onset and severity of the symptoms, patients present with either an early infantile (EI), a late infantile (LI), or a juvenile/adult (J/A) form of the disease. To study genotype-phenotype correlation in this disorder, we have analyzed the mutations in the PPCA gene of eight clinically different patients. In two EI and one J/A patient, we have identified four novel point mutations (Val104Met, Leu208Pro, Gly411Ser and Ser23Tyr), that prevent phosphorylation and, hence, lysosomal localization and maturation of the mutant precursors. Two amino acid substitutions (Phe412Val and Tyr221Asn) are shared by five LI patients. These mutations appear to be pathognomonic for this phenotype, and determine the clinical outcome depending on whether they are present together or in combination with other mutations. The latter include a single base deletion and a novel amino acid change (Met378Thr), which generates an additional glycosylation site. Within the LI group, patients carrying the Phe412Val mutation are clinically more severe than those with the Tyr221Asn substitution. This is in agreement with the biochemical behavior of the Asn221-mutant protein, that is, like the Phe412Val protein, phosphorylated, routed to lysosomes and proteolytically processed, but its intralysosomal stability is intermediate between that of wild-type PPCA and Val412- PPCA. Overall, these results may explain the clinical heterogeneity observed in GS patients and may help to correlate mutant allelic combinations with specific clinical phenotypes.      

A circuit modification that improves mammographic phototimer performance

The typical mammographic phototimer does not track with breast thickness. For four common, relatively new mammographic units, phototimed density decreases markedly as breast thickness increases. This trend is attributed to three factors: beam hardening, film reciprocity law failure (RFL), and photosensor dark or leakage current. The contributions of these three factors were experimentally quantitated for the phototimer of a Senographé 500T mammography unit. For a phototimed 28-kVp nongrid technique, the density varied from 2.0 for a 2.5-cm-thick phantom to 0.3 for one 7.6 cm thick. Of the 1.7 difference in film density, 1.1 was attributed to beam hardening, 0.2 to RFL, and 0.4 to photomultiplier tube dark current. A circuit modification was installed in the phototimer that offsets the photomultiplier dark current and has a nonlinear response to compensate for beam hardening and RFL effects. The modified phototimer tracked to within +/- 0.06 density for a 28-kVp grid technique as phantom thickness was varied from 2.0 to 6.0 cm. Similar results were obtained for nongrid techniques.     

Retrospective geometric correlation of MR, CT, and PET images

Magnetic resonance imaging, computed tomographic, and positron emission tomographic studies of the brain provide complementary information, and many patients undergo more than one of these studies during the course of their diagnostic workup and treatment. A new technique for quantitative geometric correlation of such studies makes it possible to create integrated multimodality images by mapping features from one image onto an image obtained with another modality. The coordinate transformation between any pair of images is found by a semiautomatic algorithm for matching models of the patient's external surface as depicted in the two data sets. The resultant hybrid images, which combine complementary features of different studies, are often more useful for diagnosis and treatment planning than are the original single-modality images. The algorithm can also be used for spatial registration of baseline studies with follow-up images created with the same modality, which allows tracking of a lesion to detect subtle interval changes in size and shape. This technique can be applied to images acquired in routine clinical practice, since it is completely retrospective and does not necessitate special positioning or landmarking of the patient.