GABAergic synaptic transmission onto striatal cholinergic interneurons in dopamine D2 receptor knock-out mice.

Whole-cell or cell-attached analysis was carried out in dopamine (DA) D2 receptor (D2R) knock-out (KO) mice to elucidate the function of this receptor in the regulation of GABAergic synaptic transmission onto striatal cholinergic interneurons as well as their spontaneous firing. In slice preparation obtained from wild-type mice, evoked GABAergic inhibitory postsynaptic currents (IPSCs) showed frequency-dependent suppression, and this suppression significantly decreased in the presence of a D2-like receptor antagonist or in D2R KO mice. Contribution of N-type calcium channel was also significantly reduced in the striatal cholinergic interneurons of the D2R KO mice compared with that in the wild-type mice. Spontaneous firing of striatal cholinergic interneurons was inhibited by 5- or 10-Hz stimulation, and the suppression was decreased in the presence of a D2-like receptor antagonist or in D2R KO mice. These findings substantiate the physiological role of D2R in the regulation of GABAergic synaptic transmission onto striatal cholinergic interneurons as well as their excitability, confirming the tight coupling between D2R and N-type calcium channels in the regulation of GABA release.

Mutational analyses in four Japanese families with X-linked liver phosphorylase kinase deficiency type 1.

We analysed the gene of the human alpha-subunit of liver phosphorylase kinase (PHKA2) in four Japanese families with X-linked liver phosphorylase kinase deficiency type 1 by RT-PCR followed by PCR-single-strand conformation polymorphism and direct DNA sequencing. In this study, two novel mutations (Y116D and 2675A-->G) and one mutation previously reported (P1205L) were identified, revealing molecular heterogeneity in Japanese patients. Considering the dissimilarity in phenotype among our patients even with an identical mutation in the PHKA2 gene, it seems that each genetic deficiency in this gene may not be the only factor to determine the clinical heterogeneity in this disease.

An autopsy case of hypertrophic cardiomyopathy with pathological findings suggesting chronic myocarditis.

Myocardial fibrosis in patients with hypertrophic cardiomyopathy (HCM) may play an important role in the function and/or dimensions of the left ventricle. We present an autopsied case of HCM followed for 10 years. A 68-year-woman with HCM underwent trans-aortic myectomy of the interventricular septum in 1979. A significant amount of round cell infiltration, myocardial fibrosis and disarray were observed in the resected specimen. She experienced repeated admissions due to diabetes mellitus and congestive heart failure, and died of renal failure in 1989. An autopsy revealed extensive myocardial fibrosis and significant cell infiltration in the ventricular myocardium. The infiltrating cells were almost all lymphocytes, and the ratio of CD4 to CD8 was 3.8. This ratio was different from that of typical viral myocarditis. This case suggests that there may be an undefined inflammatory process causing fibrosis in HCM, in addition to the ischemia due to intramural small coronary artery stenosis.

[Echocardiography of ischemic heart disease simulating dilated cardiomyopathy, with special reference to abnormal wall movement on the short-axis].

The purpose of this study was to determine whether two-dimensional echocardiography (2DE) can differentiate ischemic myocardial disease (IMD) from dilated cardiomyopathy (DCM). The subjects consisted of six cases of IMD which showed left ventricular dilatation (LVDd greater than or equal to 60 mm) and diffuse abnormality of wall motion, but did not show obvious localized myocardial infarction or left ventricular aneurysm on 2DE, and 16 cases of DCM. Two cases of IMD had previous myocardial infarction, and five cases of DCM had cardiomegaly following myocarditis. A short-axis image of the left ventricle was recorded at the chordal and the papillary muscle levels. Each image was divided into 4 segments, which were comprised of the septum, anterior wall, lateral (posterolateral) wall, and posterior (posteromedial) wall. Regional wall motion abnormality with reference to systolic thickening was analyzed qualitatively in each segment. The results were as follows: In ECG findings in IMD group, only one case showed abnormal Q waves and five cases showed left ventricular hypertrophy (LVH) similar to intraventricular conduction defect. On the other hand, in DCM group seven cases showed abnormal Q waves and five cases showed LVH. Two cases of IMD had two-vessel disease and four three-vessel disease, respectively. Left ventricular ejection fraction by cine-angiography ranged from 0.10 to 0.39 (mean 0.24) in IMD group and from 0.22 to 0.42 (mean 0.36) in DCM group. Mean LVDd showed no significant difference between these two groups. Five cases of DCM showed marked left ventricular dilatation (LVDd greater than or equal to 75 mm), but there were no such cases in IMD group. B-B' step was recognized in only one case of IMD, though it was present in eight cases in DCM. In regional wall motion, incidence of asynergy such as akinesis or dyskinesis was higher in IMD group than in DCM group. Left ventricular asynergy was more serious in the posteromedial wall than the posterolateral wall at the same image in five cases of IMD. However, in 12 cases of DCM, the degree of asynergy was equal at the both walls. In conclusion, it is recommended to examine echocardiographically the extent of severe asynergy in the posteromedial and posterolateral walls in order to differentiate IMD from DCM.