Proton MR spectroscopic findings in paroxysmal kinesigenic dyskinesia

Although paroxysmal kinesigenic dyskinesia (PKD) has characteristic clinical features, the pathophysiology of PKD has remained unknown. The purpose of this study was to investigate the pathophysiology of idiopathic PKD by performing proton magnetic resonance spectroscopy (1H-MRS) in five patients with idiopathic PKD. Three patients were familial and two sporadic. Single-voxel 1H-MRS was performed on a GE 1.5-T SIGNA MR system. Localized 1H-MR spectra were obtained from the basal ganglia (n = 5), thalamus (n = 3), and supplementary motor area (SMA; n = 4) using STEAM sequence (stimulated echo acquisition mode; TR = 3.0 sec, TE = 30 msec, 64 AVG, volume = 8 mL) or PRESS (point resolved spectroscopy; TR = 3.0 sec, TE = 135 msec, volume = 4 mL). Peak ratios of Cho/Cr (Cho: choline, Cr: creatine) and mI/Cr (mI: myoinositol) were decreased significantly in the unilateral basal ganglia of two patients. In one, decreased peak ratio of mI/Cr in the unilateral basal ganglia was the only abnormality. In the remaining two, there was no significant abnormality. 1H-MR spectra obtained from the thalamus and SMA were all within normal limits. In conclusion, these results suggest that underlying pathophysiological mechanism of PKD may be at least partially associated with the dysfunction of cholinergic system in the basal ganglia.     

Efficient expression of CFTR function with adeno-associated virus vectors that carry shortened CFTR genes

Adeno-associated virus (AAV)-based vectors have been shown to be effective in transferring the cystic fibrosis gene (CFTR) into airway epithelial cells in animal models and in patients. However, the level of CFTR gene expression has been low because the vector cannot accommodate the CFTR gene together with a promoter. In this study, we described a strategy to reduce the size of the CFTR cDNA to allow the incorporation of an effective promoter with the CFTR gene into AAV vectors. We engineered and tested 20 CFTR mini-genes containing deletions that were targeted to regions that may contain nonessential sequences. Functional analyses showed that four of the shortened CFTRs (one with combined deletions) retained the function and the characteristics of a wild-type CFTR, as measured by open probability, time voltage dependence, and regulation by cAMP. By using an AAV vector with a P5 promoter, we transduced these short forms of CFTR genes into target cells and demonstrated high levels of CFTR expression. We also demonstrated that smaller AAV/CFTR vectors with a P5 promoter expressed the CFTR gene more efficiently than larger vectors or a vector in which CFTR gene was expressed from the AAV inverted terminal repeat sequence. The CFTR mini-gene with combined deletions was packaged into AAV virions more efficiently, generated higher titers of transducing virions, and more effectively transferred CFTR function into target cells. These new vectors should circumvent the limitations of AAV vector for CFTR expression. Our strategy also may be applicable to other genes, the sizes of which exceed the packaging limit of an AAV vector.     

Efficacy of monensin for the prevention of subclinical ketosis in lactating dairy cows

A total of 1010 dry cows and pregnant heifers was randomly selected from 25 dairy farms near Guelph, Ontario, Canada to receive either a controlled-release capsule of monensin or a placebo at 3 wk prior to expected calving. Serum samples were obtained at the time of treatment administration, and both serum and milk samples were collected at wk 1, 2, 3, 6, and 9 postcalving. The threshold used to define subclinical ketosis was selected a priori at a concentration of > or = 1200 mumol/L of beta-hydroxybutyrate. Using this threshold, the prevalence and incidence of subclinical ketosis were significantly reduced (50%) by monensin treatment. The duration of subclinical ketosis for cows that had been treated with monensin was also shorter than that for cows treated with the placebo. Monensin treatment significantly reduced the incidence of subclinical ketosis when the threshold was defined using higher concentrations of serum beta-hydroxybutyrate (1400 and 2000 mumol/L). In addition, monensin significantly reduced the prevalence of positive milk ketone tests.     

Change in envelope beats as a possible cue in comodulation masking release (CMR)

The detection advantage associated with masker envelope coherence across frequency has typically been described in terms of comparisons of information across auditory channels. More recently it has been suggested that analysis of the output of a wider initial filter, similar to that suggested for the TMTF, can account for the data [B. G. Berg, J. Acoust. Soc. Am. 100, 1013-1023 (1996)]. This approach suggests that a change in envelope beats could serve as the cue to the addition of a pure-tone signal. Data are presented here for the detection of a tone added to multiple maskers with coherent envelopes. In one condition a change in envelope beats was an accurate potential cue, whereas in others the change was too unreliable to serve as an indicator of the presence of the signal. All conditions employing maskers with coherent envelopes produced very similar thresholds, and all showed improved sensitivity over the case of detecting a signal added to a single masker centered on the signal frequency. Results are interpreted as evidence that a change in envelope beats does not form the basis of detection in CMR.     

Audit of diagnostic criteria for Trichomonas vaginalis in a genitourinary medicine clinic

A comparison between high vaginal swab (HVS) wet prep examination within the genitourinary medicine (GUM) clinic and that made from an HVS transported in Amies charcoal medium to the laboratory for the diagnosis of Trichomonas vaginalis was made in a prospective study. Clinic wet prep compared with Amies had a sensitivity of 68% and specificity of nearly 100%. Using the clinic wet prep alone, 9/30 (30%) cases would have been missed.     

Evidence of multiple mechanisms of avermectin resistance in haemonchus contortus--comparison of selection protocols

The ginsenosides Rb1 and Rg1, the major components of ginseng saponin, inhibited not only methamphetamine-induced hyperactivity but also conditioned place preference (CPP) in mice following a single or repeated administration. Dopamine (DA) receptor supersensitivity, which developed in methamphetamine-induced CPP mice, was also inhibited by both Rb1 and Rg1. Therefore, the present results suggest that Rb1 and Rg1 may be the active components of ginseng saponin in the modulation of methamphetamine-induced dopaminergic behaviors such as hyperactivity and CPP, supporting our previous conclusion that ginseng saponin might modulate methamphetamine-induced dysfunction at both the pre- and postsynaptic DA receptors.