FM sonography in diffuse liver disease: prospective assessment and blinded analysis

FM sonography - a signal-processing technique that uses frequency and phase information as well as amplitude data - shows promise in evaluation of patients with diffuse liver disease. In a prospective blinded review of 37 patients with biopsy-proved liver disease and 42 healthy volunteers, FM sonography was clearly superior to traditional amplitude-based (AM) sonography in distinguishing healthy from diseased subjects. Statistically significant differences were seen in accuracy (FM, 98.7%; AM, 84.8%), sensitivity (FM, 97.3%; AM, 70.3%), and negative predictive value (FM, 97.7%; AM, 78.8%). Our data also suggest that current FM sonographic techniques cannot differentiate among histologic findings associated with different hepatic parenchymal abnormalities. It is unclear, therefore, whether FM imaging can reduce the numbers of patients who require biopsy for diagnosis or the frequency of biopsy procedures in patients with known disease.     

用于筛选天然产物中脲酶抑制剂的脲酶活性测试方法的建立

抑制幽门螺杆菌产生的脲酶具有治疗胃炎和消化性溃疡的作用。用酚红指示剂和Ｂｅｒｔｈｅｌｏｔ试剂在９６孔培养板上检测重组脲酶活性，其灵敏度指标酚红法每ｍｇ酶蛋白引起的每分钟吸光度变化。△Ａ为６．９，而Ｂｅｒｔｈｅｌｏｔ法每ｍｇ酶蛋白引起的每分钟吸光度比值变化△Ａ为３１３。结果表明用Ｂｅｒｔｈｅｌｏｔ试剂检测重组脲酶活性适宜在９６孔培养板上大规模筛选天然产物中的脲酶抑制剂。     

Location of motoneurones projecting to the cat distal forelimb. II. Median and ulnar motornuclei

The position of the motornuclei projecting through the median (Mn) and ulnar (Ul) nerves to the cat distal forelimb has been investigated. Horseradish peroxidase (HRP) and fluorescent (Fl) compounds have been used as retrograde tracers. They were either injected into forelimb muscles or applied to the proximal end of transected forelimb nerves. Limb muscles that were not investigated were carefully denervated. The position and the architecture of the individual motornuclei were traced with HRP. The topographical relations between the nuclei were established with application of up to three different Fl compounds in the same animal. The Mn motoneurones had a bimodal distribution in the brachial spinal cord. The motoneurones to the pronator teres and flexor carpi radialis muscles were located in C7 and the other Mn motoneurones were located in C8 and Th1. In C7 the Mn motoneurones occupied a single representation area, which is located some distance medially of the lateral funiculus. In C8 and Th1 two Mn representation areas were found: A dorsal one that contacts the lateral funiculus and is located at the level of the central canal; a ventral one that is located ventrally in the ventral horn. The dorsal area is occupied by the motornuclei projecting to the intrinsic hand muscles and the ventral one by the nuclei projecting to the limb. The Ul motoneurones extend with an unimodal distribution from the caudal C7 to the caudal Th1 segments. They occupy a single, broad representation area. The dorsal part, which contacts the lateral funiculus, is located at the level of the central canal and harbours the nuclei to the intrinsic hand muscles. The other Ul nuclei are located ventromedially deep in the ventral horn. These results, together with those from the companion paper on the location of the deep radial motornuclei, provide important anatomical information for the investigation of the cat brachial enlargement.     

Identification of non-amplifying CYP21 genes when using PCR-based diagnosis of 21-hydroxylase deficiency in congenital adrenal hyperplasia (CAH) affected pedigrees

Steroid 21-hydroxylase deficiency is among the most common inborn errors of metabolism in man. Characterization of mutations in the 21- hydroxylase gene (CYP21) has permitted genetic diagnosis, facilitated by the polymerase chain reaction (PCR). The most common mutation is conversion of an A or C at nt656 to a G in the second intron causing aberrant splicing of mRNA. Homozygosity for nt656G is associated with profoundly deficient adrenal cortisol and aldosterone synthesis, secondary hypersecretion of adrenal androgens, and a severe form of congenital adrenal hyperplasia (CAH) characterized by ambiguous genitalia and/or sodium wasting in newborns. During the course of genetic analysis of CYP21 mutations in CAH families, we and others have noticed a number of relatives genotyped as nt656G homozygotes, yet showing no clinical signs of disease. A number of lines of evidence have led us to propose that the putative asymptomatic nt656G/G individuals are incorrectly typed due to dropout of one haplotype during PCR amplification of CYP21. For prenatal diagnosis, we recommend that microsatellite typing be used as a supplement to CYP21 genotyping in order to resolve ambiguities at nt656.      

Responsiveness of C-fiber nociceptors to punctate force-controlled stimuli in isolated rat skin: lack of modulation by inflammatory mediators and flurbiprofen

Although cutaneous C-fiber nociceptors show dramatic inflammatory sensitization to heat, they do not appear to get sensitized to the mechanical stimulation by von Frey hairs. We employed force-controlled punctate electromechanical stimulation to receptive fields of 61 characterized C-fibers in the isolated rat skin-saphenous nerve preparation. In general: low-in contrast to higher-threshold units showed greater dynamic sensitivity and response magnitude, an earlier onset and a stronger degree of adaptation, the latter due to the linear rise of the force stimulus. On this methodological basis three groups of units were subject to a mix of inflammatory mediators, to flurbiprofen or to control solution. Subsequent mechanostimulation revealed a good reproducibility of the control response and no significant changes in the treatment groups. In conclusion, even refined mechanostimulation was unable to demonstrate sensitization of the predominant nociceptor classes in the rat skin.     

Sensitization of nociceptive cutaneous nerve fibers from the rat's tail by noxious mechanical stimulation

Summary This single fiber study on rat tail nerve afferents attempts to establish a peripheral neural correlate for the hyperalgesia to mechanical stimulation which follows injury to the skin. Mechano-heat sensitive C fibers (MH-C or polymodal nociceptors) and high-threshold mechanoreceptive A delta fibers (HTM-A delta) were examined with a series of constant noxious pressure stimulations (4-6-8-4 N on 25 mm², 120 s each, 5 min intervals). These injurious stimuli were either directed to the most sensitive spot of the receptive fields (central stimulation) or closely outside their borders (1–5 mm). With this protocol no clear sensitization was seen in MH-C fibers apart from a stronger dynamic response to central stimulation in some of them. In contrast, most HTM-A delta units, irrespective of the site of noxious stimulation, developed spontaneous activity, lowering of their von Frey thresholds and expansion of their receptive fields. All HTM-A delta units responded to outside stimulation: upon the first stimulus (4 N) there was a delayed discharge of continuously increasing frequency (recruited response), but the onset of the last stimulation (4 N repeated) evoked vigorous dynamic responses in many fibers. The recruitment of HTM-A delta nociceptor activity may contribute to post-injury hyperalgesia to mechanical stimulation and it may counteract adaptation of the single afferent fiber during prolonged noxious influence.On leave from the Laboratoire de Physiologie, Faculté de Médecine Lyon-Sud, Chemin du Petit Revoyet, F-69600 Ouillins, France