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11.
Amount and distribution of dietary protein affects clinical response to levodopa in Parkinson's disease 总被引:1,自引:0,他引:1
Reducing dietary protein improves the effectiveness of levodopa (LD) but the most effective distribution of a low-protein diet (0.8 g/kg) is unclear. We compared a 1.6 g/kg protein diet, a 0.8 g/kg diet with protein evenly distributed between meals, and a 0.8 g/kg diet with protein restricted to the evening meal in 5 parkinsonian patients with motor fluctuations. We monitored clinical response, plasma LD, and plasma large amino acids (LNAAs) hourly throughout the day. Mean "on" times were 51% (1.6 g/kg diet), 67% (0.8 g/kg evenly distributed), and 77% (0.8 g/kg restricted). Hourly averages of plasma LD did not differ between the diets. The mean plasma LNAAs were 732 nmol/ml (1.6 g/kg diet), 640 (0.8 g/kg distributed), and 542 (0.8 g/kg restricted), and the diurnal pattern reflected the distribution of protein intake. In conclusion, the amount and distribution of dietary protein affect clinical response to LD. These effects are not related to LD absorption but are explained by the variation in plasma LNAAs. 相似文献
12.
Day DJ; Speiser PW; Schulze E; Bettendorf M; Fitness J; Barany F; White PC 《Human molecular genetics》1996,5(12):2039-2048
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.
相似文献
13.
14.
Physical characteristics of the ECAT EXACT3D positron tomograph 总被引:9,自引:0,他引:9
Spinks TJ Jones T Bloomfield PM Bailey DL Miller M Hogg D Jones WF Vaigneur K Reed J Young J Newport D Moyers C Casey ME Nutt R 《Physics in medicine and biology》2000,45(9):2601-2618
The 'EXACT3D' positron tomograph, which is now in routine clinical research use, was developed with the aim of achieving unprecedented sensitivity, high spatial and temporal resolution and simplicity of design using proven detector technology. It consists of six rings of standard detector blocks (CTI/Siemens EXACT HR+) with 4.39 mm x 4.05 mm x 30 mm elements, giving an axial field of view (FOV) of 23.4 cm. This extended FOV and the absence of interplane septa and retractable transmission rod sources has allowed greatly simplified gantry and detector cassette design. Operation in exclusive 3D mode requires an alternative to the conventional coincidence method for transmission scanning, and a single photon approach using a hydraulically driven 137Cs point source has been implemented. The tomograph has no other moving parts. A single time frame of data without any compression is very large (> 300 Mbyte) and two approaches are employed to overcome this difficulty: (a) adjacent sinograms can be summed automatically into different combinations and (b) listmode (event-by-event) acquisition has been instituted, which is both storage efficient (particularly for acquisition of sparse data sets) and maximizes temporal resolution. The high-speed I/O and computing hardware can maintain a sustained acquisition rate of about 4 million coincidence events per second. A disadvantage of the large axial FOV in 3D is the increased sensitivity to activity outside the coincidence FOV. However, this can be minimized by additional side shielding. The mean spatial resolution is 4.8 +/- 0.2 mm FWHM (transaxial, 1 cm off-axis) and 5.6 +/- 0.5 mm (axial, on-axis). Its absolute efficiency is 5.8% for a line source in air (just spanning the axial FOV) and 10% for a central point source (with thresholds of 350-650 keV). For a uniform 20 cm diameter cylinder, the efficiency is 69 kcps kBq(-1) ml(-1) (after subtraction of a scatter fraction of 42%). Sensitivity relative to the EXACT HR+ (with four rings of blocks) is 2.5 (3D) and 12 (2D) times respectively. The rate of random events in blood flow studies in the brain and body, using 15O-labelled water, can be controlled by limiting the administered dose and inserting additional side shielding. 相似文献
15.
The GAP-related domain of tuberin, the product of the TSC2 gene, is a target for missense mutations in tuberous sclerosis 总被引:5,自引:0,他引:5
Maheshwar MM; Cheadle JP; Jones AC; Myring J; Fryer AE; Harris PC; Sampson JR 《Human molecular genetics》1997,6(11):1991-1996
Tuberous sclerosis is an autosomal dominant trait in which the
dysregulation of cellular proliferation and differentiation results in the
development of hamartomatous growths in many organs. The TSC2 gene is one
of two genes determining tuberous sclerosis. Inactivating germline
mutations of TSC2 in patients with tuberous sclerosis and somatic loss of
heterozygosity at the TSC2 locus in the associated hamartomas indicate that
TSC2 functions as a tumour suppressor gene and that loss of function is
critical to expression of the tuberous sclerosis phenotype. The TSC2
product, tuberin, has a region of homology with the GTPase activating
protein rap1GAP and stimulates the GTPase activity of rap1a and rab5a in
vitro. Here we show that the region of homology between tuberin and human
rap1GAP and the murine GAP mSpa1 is more extensive than previously reported
and spans approximately 160 amino acid residues encoded within exons 34-38
of the TSC2 gene. Single strand conformation polymorphism analysis of these
exons in 173 unrelated patients with tuberous sclerosis and direct
sequencing of variant conformers together with study of additional family
members enabled characterisation of disease associated mutations in 14
cases. Missense mutations, which occurred in exons 36, 37 and 38 were
identified in eight cases, four of whom shared the same recurrent change
P1675L. Each of the five different missense mutations identified was shown
to occur de novo in at least one sporadic case of tuberous sclerosis. The
high proportion of missense mutations detected in the region of the TSC2
gene encoding the GAP-related domain supports its key role in the
regulation of cellular growth.
相似文献
16.
Bell C Vanderlinden H Hiersemenzel R Otoul C Nutt D Wilson S 《Journal of sleep research》2002,11(3):255-263
Levetiracetam is a novel antiepileptic drug which has recently been released as an adjunctive treatment for partial epilepsy. In the two studies reported here we examined the objective and subjective effects of levetiracetam on sleep in 12 healthy volunteers and 17 patients [16 who could be evaluated for electroencephalogram (EEG) recordings] with a history of partial epilepsy on stable carbamazepine monotherapy. The studies were of a similar double-blind crossover placebo-controlled design with subjects' sleep being recorded in their own homes. The results from the two studies showed considerable similarities. In both, levetiracetam produced an increase in the time spent in stage 2 sleep, which in the patient study was accompanied by a decrease in the time spent in stage 4 sleep and in the volunteer study an increase in rapid eye movement (REM) latency. The subjective changes included reports that sleep was of a better quality with fewer awakenings and patients also reported that their sleep was more restful. Volunteers and patients did, however, feel less alert on waking in the morning. Therefore, both groups reported a decrease in awakenings after levetiracetam despite the finding from the EEG of no change in the actual number of awakenings. It may be concluded from both studies that levetiracetam does affect some indicators of subjective sleep perception, but does not influence objective sleep measures of sleep continuity. The results from the patient study during placebo add-on treatment also showed that patients on carbamazepine had a marked increase in SWS, an increase in stage 2 sleep and an increase in REM latency compared with healthy volunteers. Interestingly, levetiracetam also reduced bilateral epileptiform EEG activity, particularly in patients with more discharges. 相似文献
17.
Glycoproteins present in human follicular fluid that inhibit the zona- binding capacity of spermatozoa 总被引:1,自引:0,他引:1
Previous studies have suggested that human follicular fluid contains
factors that reduce the zona-binding capacity of spermatozoa. The present
study provides further evidence of the existence of such factors. Using the
hemizona binding assay (HZA), we have shown that the inhibitory effect of
human follicular fluid on the zona-binding capacity of spermatozoa is
concentration-dependent, an inhibitory effect being detected when the
concentration of human follicular fluid was > or = 10%. A 1%
concentration of human follicular fluid did not possess this inhibitory
activity. Heating human follicular fluid at 56 degrees C for 30 min did not
affect its inhibitory properties; treatment with proteinase-K abolished
such inhibition. Human follicular fluid was fractionated sequentially by
concanavalin-A affinity chromatography, Mono Q ion-exchange chromatography
and Superose-12 gel filtration. The zona binding inhibitory activity
resided in the fraction which bound to the lectin and Mono Q column and
contained molecules with native molecular weights of 32 and 192 kDa. Sodium
dodecyl sulphate-polyacrylamide gel electrophoresis analysis suggested that
the 192 kDa glycoprotein was a tetramer, while the 32 kDa glycoprotein
remained as a single molecular species under denaturing conditions. We
conclude that two glycoproteins were responsible for the zona binding
inhibitory activity of human follicular fluid. The physiological role of
these factors remains unclear.
相似文献
18.
The postural adaptation impairments of patients with Parkinson's disease (PD) suggest that the basal ganglia may be important for quickly modifying muscle activation patterns when the direction of perturbation or stance conditions suddenly change. It is unknown whether their particular instability to backward postural perturbations is due to specific abnormalities of parkinsonian postural muscle synergies in that direction and not present in other directions. In the present study, we test this hypothesis by comparing the patterns of leg and trunk muscle activation in 13 subjects with PD and 13 control subjects in response to eight randomly presented directions of horizontal surface translations while standing with either narrow or wide stance. The direction of maximum activation for each muscle was similar for PD and control subjects, suggesting that the basal ganglia is not critical for programming externally triggered postural synergies. However, antagonist muscle activation was earlier and larger in PD than in control subjects, resulting in coactivation. PD subjects also did not increase the magnitude of muscle activation as much as did control subjects when changing from wide to narrow stance. These results are consistent with the hypothesis that PD results in an inability to shape the pattern and magnitude of postural muscle responses for changes in perturbation direction and in stance position. 相似文献
19.
Genetic alterations of phosphoinositide 3-kinase subunit genes in human glioblastomas 总被引:1,自引:0,他引:1
Genetic alterations of PI3K (phosphoinositide 3-kinase) subunits have been documented in a number of tumor types, with increased PI3K activity linked to gene amplification and mutation of catalytic subunits, as well as mutations of regulatory subunits. Among high grade gliomas, activation of the PI3K-AKT signaling pathway through loss of PTEN function is common. We therefore investigated whether genetic alteration of class IA PI3Ks might provide a mechanism for deregulation of this pathway in glioblastomas. We studied a series of glioblastomas with FISH to assess copy number of catalytic subunits (PIK3CA and PIK3CD) and with PCR-SSCP to screen for somatic mutations of conserved regions of both catalytic and regulatory subunits. FISH revealed frequent balanced copy number increases of both PIK3CA and PIK3CD, and one case showed an extra copy limited to PIK3CA. One glioblastoma exhibited a 9-bp deletion that encompassed the exon-intron junction of exon 12 of PIK3R1, documenting for the first time a mutation within a PI3K regulatory subunit in human glioblastoma. This deletion would be predicted to yield a truncated protein that lacks the inhibitory domain, resulting in increased PI3K activity. Furthermore, the case with selected PIK3CA copy number gain and the case with a truncating PIK3R1 mutation both featured AKT activation without PTEN mutation. These results suggest that genetic alterations of class IA PI3K subunit genes can occasionally play a role in human glioblastoma by activating the PI3K-AKT signaling pathway independently of PTEN mutation. 相似文献
20.
Michaël Chopin Aaron T. Lun Yifan Zhan Jaring Schreuder Hannah Coughlan Angela D’Amico Lisa A. Mielke Francisca F. Almeida Andrew J. Kueh Ross A. Dickins Gabrielle T. Belz Shalin H. Naik Andrew M. Lew Phillipe Bouillet Marco J. Herold Gordon K. Smyth Lynn M. Corcoran Stephen L. Nutt 《Immunity》2019,50(1):77-90.e5