Since patients with Friedreich's ataxia appear to oxidize pyruvate slowly, we measured the activity of the pyruvate dehydrogenase complex in disrupted fibroblasts from four patients with this syndrome and one patient with a clinical variant. The activity was 43 +/- 4 per cent of that in 16 controls (mean +/- S.E.M., P less than 0.001). The activity of the 2-oxoglutarate dehydrogenase complex was also lower in the patients' cells than in those of controls (50 +/- 2 per cent, P less than 0.001). However, the activity of cytochrome-c oxidase was normal (126 +/- 43 per cent of controls). Mixing experiments gave no evidence of soluble enzyme inhibitors or activators, and the addition of excess substrate or cofactor did not ameliorate the deficiencies. White blood cells from one of the patients had low activities of both complexes. Mutations of these dehydrogenase complexes occur in some patients with Friedreich's ataxia and lead to abnormally low activity of an enzyme of the tricarboxylic acid cycle.

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authors request that the following correction be noted. Our conclusion that the APP gene maps very near the 21q21/21q22 border is consistent with the mapping by in situ hybridization to the interface of these two chromosomal bands as reported by Blanquet et al. (1,2) and reported in an abstract by Zabel et al. (3). Unfortunately, we were not familiar with this material. Nevertheless, the situation as it stood before our publication involved the mapping ofthe APP gene by in situ hybridization to two different locations on chromosome 21, one of which would have excluded it from the region of the chromosome pathogenic for Down syndrome. In situ hybridization has, in other important cases, led to incorrect mapping of genes. Therefore, other approaches were required. Our paper presents mapping by other, more reliable methods. In addition, our in situ hybridization was confirmed using a completely different and unrelated DNA probe that we had linked physically to the APP locus by using transverse alternating field electrophoresis, so that we have further independent confirmation of our mapping.

A b s t r a c t . U s i n g a new n i t r i c o x i d e a n a l y s e r , we h a v e d e v e l o p e d a s e n s i t i v e c h e m i l u m i n e s c e n c e a s s a y t o d e t e c t t r a c e q u a n t i t i e s o f NO i n a q u e o u s s o l u t i o n s . T h i s improved t e c h n i q u e i n c o m b i n a t i o n w i t h t h e b i o a s s a y h a s b e e n employed t o v e r i f y t h e t h e o r y t h a t NO r e l e a s e d by v a s c u l a r e n d o t h e l i u m , a c c o u n t s f o r t h e I n t r o d u c t i o n . N i t r i c o x i d e has been i m p l ic a t e d as t h e e n d o t h e l i u m -d e r i v e d r e l a x i n g f a c t o r (EDRF) , whi ch mediates t h e vascul a r r e l a x a t i o n produced by a c e t y l c h o l i n e and c a l c i u m ionophore A23187 ( I ,2). R e c e n t l y we have demonstrated t h a t 1ysop;;;sphatidyl c h o l i n e (LPC) a1 so produces endothelium-dependent r e l a x a t i o n o f r a b b i t t h o ra c i c a o r t a as w e l l as b o v i n e i n t r a p u l m o n a r y a r t e r y and v e i n ( 3 -6 ) . The n a t u r e o f t h e r e l a x i n g substance produced b y LPC has n o t been determined. The i d e a t h a t EDRF c o u l d be NO emerged f r o m a n a lagous f i n d i n g s w i t h n i t r o v a s o d i l a t o r s , a c i d i f ic a t i o n o f i n o r g a n i c n i t r i t e which generates NO, and t h e v a s c u l a r r e l a x i n g e f f e c t s o f aqueous s o l u t i o n s of NO gas i n s u p e r f u s i o n cascade b i oassays (7-9 ) . The chemical assays f o r t h e det e c t i o n NO have u t i l i z e d t h e chemiluminescence r e a c t i o n o f NO w i t h ozone t o f o r m NO2, o r t h e i n t h e presence and absence of a c i d . I n c o m b i n a t i o n w i t h b i o a s s a y s u p e r f u s i o n experiments t h i s t e c hn i q u e i s more d i r e c t and s e n s i t i v e f o r t h e det e c t i o n o f NO t h a n those p r e v i o u s l y described. F l a t e r i a l s and ~e t h o d s . ~e t e c t i o n o f n i t r i c o x i d e . N i t r i c Oxide A n a l v s e r (NOA) model 270 was purchased f r o m s i e v e & ~e s e a r c i i , I n c . , ~o u l d e r , CO. D e t e c t i o n o f NO i s based on t h e chemiluminescence r e a c t i o n of NO w i t h ozone. t o t h e NOA. The l e a k -? r o o f purge and t r a p d e v i c e c o n s i s t s o f a p u r g i n g u n i t made o f b o r o s i l i c a t e g l a s s (7.5 cm X 1.27 cm) w i t h a g l a s s b u l b (3.7 cm) a t t h e t o p and a medium p o r o s i t y g l a s s f r i t a t t h e bottom. T h i s i s connected by a U-tube and an o b l i q u e h i g h vacuum cup stopcock t o an i n l e t o f he1 ium. The p o r t a t t h e t o p p e r m i t s i n t r od u c t i o n and removal of samples. The s i d e arm on t h e b u l b i s connected b y a h i g h vacuum s t o pcock t o t h e NOA which i s m a i n t a i n e d under reduced p r e s s u r e (0-1 T o r r ) b y a vacuum pump (Edwards Model E2M-1). Gases f r o m t h e purge d e v i c e pass t h r o u g h a needle v a l v e t h a t r e...