Previous reports in the literature have described correlation of increasing repeat length with severity of the phenotype, in Kennedy syndrome. We describe male siblings with different repeat lengths, with lack of expression of the phenotype in the sibling with the longer repeat length. The phenotype was identical to motor neurone disease. There is variability of expression in Kennedy syndrome and repeat length even in siblings cannot be taken as a conclusive indicator of severity. CAG repeat length cannot be used to predict the natural history of Kennedy disease. The diagnosis of Kennedy syndrome should be considered in male patients presenting with atypical motor neurone disease. 相似文献
Background: Acetaminophen (paracetamol) is widely used for postoperative analgesia. Its mechanism of action is inhibition of prostaglandin synthesis in the central nervous system, and acetaminophen is traditionally not considered to influence platelet function. The authors studied the dose-dependent inhibition of platelet function by acetaminophen in healthy volunteers.
Methods: Thirteen healthy male volunteers (aged 19-26 yr) were given placebo or 15, 22.5, or 30 mg/kg acetaminophen intravenously in a double-blind, crossover study. Ten and 90 min after infusion, platelet function was assessed by photometric aggregometry and by measuring release of thromboxane B2, analgesia by cold pressor test, and plasma acetaminophen concentrations by high-performance liquid chromatography.
Results: When triggered with 500 [mu]m arachidonic acid, median platelet aggregation (area under the curve) was 25.7, 22.8, 4.1, or 3.6 x 103 area units (P < 0.001) 10 min after placebo or 15, 22.5, or 30 mg/kg acetaminophen, respectively. An increasing concentration of arachidonic acid attenuated the antiaggregatory effect. After 90 min, platelet function was recovering. Release of thromboxane B2 was also dose-dependently inhibited by acetaminophen. Although plasma concentration of acetaminophen increased linearly with the dose, no analgesic effect was detected in the cold pressor test. 相似文献
From the experiments described, it can be seen that there are different
research approaches that can be taken and these are summarized in Table 1.
Whereas much scientific research is principally hypothesis led, there
remains, nevertheless, an important place for exploratory research. High
resolution NMR can measure, directly and simultaneously, a wide range of
endogenous metabolites in biological fluids and has the unique capability
of providing structural information on the metabolites detected. It has
proved to be a powerful research tool with which to study inherited
metabolic diseases, renal disease, drug metabolism, and toxicity, and can
be used to monitor the effects of drug therapy. For instance, by using a
library of experimental toxins one can map the metabolic profile of
site-specific nephron injury. With this approach in man one could
eventually take an unknown disease such as Balkan nephropathy and predict
the initial site of tubular injury, the mode of injury and therefore the
kind of toxin capable of producing that injury. NMR spectroscopic
techniques are still advancing rapidly, with ever increasing sensitivity
and sophistication of NMR pulse sequences to enhance structural elucidation
in complex mixtures. Given the advances in directly coupled HPLC-NMR and
even HPLC-NMR-mass spectroscopy it is likely that these technologies in
conjunction with pattern recognition will make major contribution to our
understanding of renal processes and provide new diagnostic insights in the
21st century.
相似文献
Leukotriene B4 (LTB4) and the protein kinase C activator, 4-beta-phorbol dibutyrate (PDBu), both induced a pronounced and concentration-dependent stimulation of hydrogen peroxide (H2O2) generation by purified guinea pig peritoneal eosinophils in the concentration range 1 nM-1 microM. The LTB4 response was inhibited competitively by the specific LTB4 receptor antagonist, U-75302, with a KB of 25 nM, while the concentration-response curves for both stimuli were shifted rightwards (3.8-fold and 2.8-fold for LTB4 and PDBu, respectively) by the competitive protein kinase C inhibitor, 1-O-hexadecyl-2-O-methylglycerol at a concentration of 300 microM. LTB4 appears, therefore, to induce respiratory burst in eosinophils via a receptor-mediated mechanism involving protein kinase C. 相似文献
Twenty-four epileptic women were followed-up during late pregnancy, labor, and early puerperium in order to detect possible alterations in serum protein binding of antiepileptic drugs (AEDs). The total and free concentrations of carbamazepine (CBZ), phenytoin (PHT), and valproate (VPA) in maternal serum were measured. In addition, the concentrations of albumin, alpha 1-acid glycoprotein (AGP), and free fatty acids (FFA) were also measured. Total AED concentrations during labor were influenced by changes in drug dosages; total PHT increased during the first puerperal weeks. During labor the free fraction of CBZ remained stable, whereas PHT and particularly VPA free fractions increased. This phenomenon was parallel to the increase in FFA concentration; FFA concentrations decreased again during the first days postpartum. Albumin and AGP concentrations were low during pregnancy and labor, and increased after delivery. The total umbilical CBZ and PHT concentrations were not significantly different from maternal concentrations. The total VPA concentration in umbilical serum was significantly higher than that in maternal serum. The free fraction of CBZ was higher and that of PHT and VPA lower in umbilical than in maternal serum at delivery. Umbilical cord serum had a higher albumin but a lower AGP and FFA concentration than maternal serum. The changes in PHT and particularly VPA free fraction associated with changes in FFA concentration should be considered when assessing the total concentration of these drugs in maternal and umbilical serum. 相似文献
Among white adults otosclerosis is the single most common cause of hearing
impairment. Although the genetics of this disease are controversial, the
majority of studies indicate autosomal dominant inheritance with reduced
penetrance. We studied a large multi- generational family in which
otosclerosis has been inherited in an autosomal dominant pattern. Five of16
affected persons have surgically confirmed otosclerosis; the remaining nine
have a conductive hearing loss but have not undergone corrective surgery.
To locate the disease- causing gene we completed genetic linkage analysis
using short tandem repeat polymorphisms (STRPs) distributed over the entire
genome. Multipoint linkage analysis showed that only one genomic region, on
chromosome 15q, generated a lod score >2.0. Additional STRPs were typed
in this area, resulting in a lod score of 3.4. STRPs FES (centromeric) and
D15S657 (telomeric) flank the 14. 5 cM region that contains an otosclerosis
gene.
相似文献
X-linked liver glycogenosis type II (XLG II) is a recently described X-
linked liver glycogen storage disease, mainly characterized by enlarged
liver and growth retardation. These clinical symptoms are very similar to
those of XLG I. In contrast to XLG I patients, however, XLG II patients do
not show an in vitro enzymatic deficiency of phosphorylase kinase (PHK).
Recently, mutations were identified in the gene encoding the liver alpha
subunit of PHK (PHKA2) in XLG I patients. We have now studied the PHKA2
gene of four unrelated XLG II patients and identified four different
mutations in the open reading frame, including a deletion of three
nucleotides, an insertion of six nucleotides and two missense mutations.
These results indicate that XLG II is due to mutations in PHKA2. In
contrast to XLG I, XLG II is caused by mutations that lead to minor
structural abnormalities in the primary structure of the liver alpha
subunit of PHK. These mutations are found in a conserved RXX(X)T motif,
resembling known phosphorylation sites that might be involved in the
regulation of PHK. These findings might explain why the in vitro PHK
enzymatic activity is not deficient in XLG II, whereas it is in XLG I.
相似文献