Cortical stimulation did not augment the gains from a late rehabilitation program. The effect size anticipated by the authors was overestimated. These results can improve the design of future work on therapeutic uses of TMS.

MicroRNA-27a (miR-27a) is expressed in MCF-7 breast cancer cells, and antisense miR-27a (as-miR-27a) induces ZBTB10, a specificity protein (Sp) repressor. Both as-miR-27a and overexpression of ZBTB10 decreased Sp1, Sp3, and Sp4 mRNA and protein expression in MCF-7 cells, and this was also accompanied by decreased levels of estrogen receptor alpha (ERalpha) mRNA and protein. RNA interference studies confirmed that basal expression of ERalpha was dependent on Sp1 but not Sp3 or Sp4 in MCF-7 cells. as-miR-27a and overexpression of ZBTB10 inhibited 17beta-estradiol (E2)-induced transactivation in MCF-7 cells, and this was accompanied by decreased binding of Sp and ER proteins in cell lysates to oligonucleotides containing GC-rich motifs or estrogen-responsive elements, respectively. as-miR-27a and overexpression of ZBTB10 arrested MCF-7 cells in G(0)/G(1) and inhibited E2-induced G(0)/G(1) to S phase progression. as-miR-27a induced only a minimal increase in Myt-1, another miR-27a regulated gene, and this was not accompanied by Myt-1-dependent G(2)/M arrest as observed previously in ER-negative MDA-MB-231 breast cancer cells. Thus, miR-27a indirectly regulates E2-responsiveness in MCF-7 cells through suppression of ZBTB10, thereby enhancing expression of ERalpha.

tsl is a neurovirulent spontaneous temperature-sensitive mutant of Moloney murine leukemia virus TB which causes hindlimb paralysis in mice. Previously, it had been shown that the temperature-sensitive defect resided in the env gene. At the restrictive temperature, the envelope precursor polyprotein, gPr80env, is inefficiently processed intracellularly into two cleavage products, gp7O and Prpl5E. This inefficient processing of gPr8Oe"v is correlated with neurovirulence. In this study, it was shown that a single amino acid substitution, Val-25-Ile in gPr80"v, is responsible for the temperature sensitivity, inefficient processing of gPr8(W'v at the restrictive temperature, and neurovirulence of tsl. At the restrictive temperature, a steady-state level of nonprocessed, endoglycosidase H-sensitive gPr8Oenv remained in the endoplasmic reticulum of cells infected by tsl, but no endoglycosidase H-resistant gPr8Oe"v and only trace amounts of gp70 were detected in the infected cells. Since the host cell-encoded processing protease resides in the cis cisternae of the Golgi apparatus, inefficient processing of gPr80e"V at the restrictive temperature is. most likely due to inefficient transport of gPr8 env from the endoplasmic reticulum to the cis cisternae of the Golgi apparatus rather than due to misfolded gPr80rnV being a poor substrate for the processing protease at the restrictive temperature.

1601pathy. Only one abnormal ratio was found in the 75 diabetics of grades 0 and 1, in whom autonomic function was normal on conventional testing. In grade 2, 41 of the 47 diabetics gave abnormal or borderline results. The ratios in the 12 with symptomatic autonomic neuropathy (grade 3) were all well below the normal range.Repeat measurements of the E:I ratio varied little; the coefficients of variation were 8 9°in healthy subjects and 5 3%/ in diabetics. DiscussionMeasurement of variation in heart rate during deep breathing is generally agreed to be a sensitive index of autonomic dysfunction, comparing favourably with tests based on changes in posture.1 3 Adaptation of a repeated deep breathing test for use with a conventional electrocardiogram to obtain an E:I ratio was first described by Sundkvist et al,11 which represented a considerable simplification in technique over previous methods. These authors did not define the influence of age on this ratio but set the lower limit of normal at an E:I ratio of 1-1. When applied to the ratios measured here this limit gave three falsepositive and 16 false-negative diagnoses. The age-related normal range described in this report increases the diagnostic value of the E:I ratio test since there were only one false-positive and six false-negative results.There does not appear to be any advantage in averaging the variations in heart rate from a sequence of forced respirations compared with measuring the change resulting from a single deep breath. The change in rate is greater on the first breath1 12 and, in contrast to the mean, is not affected by the resting heart -rate,5 which simplifies the construction of a normal range.I conclude, therefore, that the E:I ratio test of sinus arrhythmia is an accurate and reliable method of screening diabetic patients for autonomic dysfunction. It may be performed rapidly by a nurse or technician with any electrocardiographic apparatus and immediate reference made to the normal range. It is thus appropriate for use in the diabetic clinic.I am grateful to the British Diabetic Association for financial support, Professor S E Smith for statistical advice, and Professor P H Sonksen and Dr C Lowy for allowing me to study their patients. ReferencesMackay Microscopic colitis-a cause of chronic watery diarrhoea JEREMY G C KINGHAM, DAVID A LEVISON, JOANNA A BALL, ANTHONY M DAWSON Abstract Six patients with severe watery diarrhoea were found to have microscopic total colitis. None had any abnormality detectable by conventional tests used to diagnose inflammatory bowel disease-namely, barium radiology and endoscopy. The diagnosis could only be made by microscopic examination of biopsy specimens from the apparently normal colon. Anaemia, raised erythrocyte sedimentation rate, hypokalaemia, and hypoalbuminaemia were common findings. Smallbowel function was normal in all, though three patients had jejunal lesions of uncertain relevance but seemingly unrelated to the diarrhoea. The five patients given anti-inflammatory drugs showed a satisfactory re...

A 68 year old man is described with an alien left hand, cortical myoclonus, bilateral parietal lobe dysfunction and memory impairment but preserved language skills. The clinical diagnosis was of corticobasal degeneration but at necropsy, four years after the onset of symptoms, the pathology was of Alzheimer's disease together with some scattered chromatolytic pale neurons in the cerebral cortex. The alien hand sign has not previously been described in Alzheimer's dementia and is an illustration of the clinical heterogeneity that may occur in association with Alzheimer histopathology.