Specific somatosensory processing in somatosensory area 3b for human thumb: a neuromagnetic study.

OBJECTIVES: We examined the relation between somatosensory N20m primary responses and high-frequency oscillations (HFOs) after thumb and middle finger stimulation. METHODS: Somatosensory evoked fields (SEFs) from 12 subjects were measured following electric stimulation of the thumb and middle finger. SEFs were recorded with a wide bandpass (3-2000 Hz) and then N20m and HFOs were separated by subsequent 3-300 and 300-900 Hz bandpass filtering. RESULTS: The N20m peak-to-peak amplitude did not differ significantly between thumb and middle finger SEFs. In contrast, HFOs had a significantly larger number of peaks and were higher in the maximum amplitude and the total amplitude after thumb stimulation than after middle finger stimulation. CONCLUSIONS: Our present data demonstrate a different relation between N20m and HFOs after thumb and middle finger stimulation. In view of the fact that the human thumb has uniquely evolved functionally and morphologically, the somatosensory information from the thumb will be processed differently for a fine motor control. We speculate that HFOs are generated by inhibitory interneurons in layer 4 in area 3b. Thus, enhanced activity of interneurons reflected by high amplitude HFOs exerts stronger inhibition on downstream pyramidal cells in area 3b for thumb stimulation.

Detection of gene-environment interaction by case-only studies.

BACKGROUND: The detection of gene-environment interaction can provide important clues not only for resolving biological mechanisms underlying diseases, but also for disease prevention. The newly introduced case-only study was compared with traditional case-control study in terms of statistical power to detect significant gene-environment interaction. METHODS: Odds ratios for interaction were calculated in the framework of case-control study and case-only study separately, by an unconditional logistic model. Hypothetical data with 200 cases and 200 or 400 controls and real published data derived from four cancer case-control studies of genotype and smoking were used for the comparisons. RESULTS: Although odds ratio estimates for interaction were the same, 95% confidence intervals were narrower in case-only studies than in case-control studies. Similarly, there were no substantial differences in point estimates for interaction in four real cancer case-control studies between the two study designs, but the confidence intervals were narrower with the case-only study. CONCLUSIONS: Although the case-only study does not provide odds ratios for exposure or genotype alone, it is very useful for the detection of interaction, especially for screening purposes.

Mapping of angiotensin II receptor subtypes in peripheral tissues of spontaneously hypertensive rats by in vitro autoradiography.

1. The regulation of angiotensin II (AII) receptor subtypes was studied in peripheral tissues of 20 week old male spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar-Kyoto (WKY) rats. 2. AII receptor binding was determined by a quantitative in vitro autoradiography using [125I]-[Sar1,Ile8]AII as a ligand on the kidney, adrenal gland, thoracic aorta and heart. CV-11974, a specific AT1 receptor antagonist, and CGP42112B, a specific AT2 antagonist, were used in competition with [125I]-[Sar1,Ile8]AII to differentiate AT1 and AT2 receptor binding. 3. The relative abundance of each subtype was very similar between SHR and WKY rats. In both strains of rats, the adrenal cortex contained predominantly AT1 receptors, while AT2 receptors predominated in the adrenal medulla. The kidney contained exclusively AT1 receptors over glomeruli, proximal tubules and outer medulla. AT1 receptors were predominant in the thoracic aorta and heart. 4. As for relative receptor density, important differences were observed between SHR and WKY rats. In SHR, the adrenal cortex, outer medulla of the kidney, and heart displayed higher AT1 receptor density than WKY rats. 5. These results indicate that the expression of AT1 receptors is differently regulated in some important targets of AII in SHR, and suggest that the altered regulation of AT1 receptor presented in this study should be relevant to the pathophysiological features of SHR.

Quantitative localization of angiotensin II receptor subtypes in spontaneously hypertensive rats.

Angiotensin II (Ang II) receptors were labelled by in vitro autoradiography using 125I-[Sar1,Ile8]Ang II as a ligand in the kidney, adrenal gland, thoracic aorta, and hindbrain of adult spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Ang II receptors were differentiated into subtypes by susceptibility to subtype 1 (AT1) and subtype 2 (AT2) antagonists. In both rat strains, the adrenal cortex contained predominantly AT1 receptors, while AT2 receptors predominated in the adrenal medulla. The kidney contained exclusively AT1 receptors in glomeruli, proximal tubules, and the outer medulla. AT1 receptors were predominant in the thoracic aorta. The nucleus of the solitary tract (NTS), dorsal motor nucleus of the vagus (DM10), area postrema, and spinal trigeminal nucleus (Sp5) contained exclusively AT1 receptors, whereas the nucleus of the inferior olive contained AT2 receptors predominantly. Significant differences in receptor density were observed between SHR and WKY. The adrenal cortex, renal outer medulla, NTS, DM10, and Sp5 displayed higher AT1 receptor density in SHR than in WKY. These results indicate that expression of AT1 receptors is regulated differently in important targets of Ang II in SHR, and suggest that altered regulation of AT1 receptor expression may be relevant to the pathogenesis of hypertension in SHR.

Pathogenetic role of vascular angiotensin-converting enzyme in the spontaneously hypertensive rat.

1. This study was undertaken to examine the possibility that the level of angiotensin-converting enzyme (ACE) increases in vascular tissue, and that this may participate in the pathogenesis of hypertension in spontaneously hypertensive rat (SHR). 2. In SHR, at the established hypertensive stage, the prolonged antihypertensive effect induced by a single oral dose of spirapril was closely correlated to the long-lasting inhibition of ACE in aortae and mesenteric arteries. In contrast, ACE in plasma, lung, heart and kidney recovered from inhibition faster than in vessels. 3. Prolonged daily oral treatment of SHR with spirapril, initiated at the age of 8 weeks and continued for 8 weeks, prevented the development of hypertension with concomitant decrease in aortic ACE activity. Blood pressure continued to be suppressed after the drug was withdrawn, as did the aortic ACE activity. 4. Spontaneously hypertensive rats developed hypertension with age as well as with the increase in aortic ACE activity which became higher with age than that of Wistar-Kyoto (WKY) normotensive control rats. On the contrary, ACE activity in plasma and lung of SHR was substantially lower than that of WKY at any age from 4 to 20 weeks old. Brain ACE activity of SHR did not differ from that of WKY at any age. Aged SHR showed the lower enzyme activity in the kidney compared with that of age-matched WKY. 5. Our results support the hypothesis that increased vascular ACE may play an essential role in the development and maintenance of hypertension in SHR.

Adrenergic regulation of estradiol uptake and cyclic GMP content in rat uterus.

The presence of adrenergic regulation of estradiol uptake in rat uterus was studied by using alpha- and beta-adrenergic blockers in normal or Ca2+-free Tyrode's solution at 30 degrees C in vitro. Cyclic GMP content was also investigated under these conditions. By the stimulation with noradrenaline (4 X 10(-7) M), Ca2+-dependent 3H-estradiol uptake was increased in both cytosol and nuclear fractions. These increases were blocked in the presence of phentolamine (4 X 10(-7) M) but not by propranolol (4 X 10(-7) M). Increase in uterine cyclic GMP contents were shown under the condition in which 3H-estradiol uptake was stimulated. These results suggest that adrenergic alpha-stimulation increased uterine estradiol uptake and that consequently, increased estradiol-receptor complexes elevated uterine cyclic GMP levels. The changes in uterine cyclic GMP may serve as an index of estrogen action.

Reversible control of oligomeric interaction of the sarcoplasmic reticulum calcium ATPase with the use of a cleavable cross-linking agent.

Reversible cross-linking with a cleavable homobifunctional reagent, dithiobissuccinimidyl propionate, of the Ca2+ ATPase polypeptides of fragmented sarcoplasmic reticulum produces oligomers in the range of 2 to 4 X 100,000 Da (cf. Louis, C. F., and Holroyd, J. A., (1979) Biochim. Biophys. Acta 535, 222-232). The presence of millimolar ATP during the dithiobissuccinimidyl propionate reaction protects the enzyme from inactivation without affecting cross-linking. In the presence of both ATP (e.g. 1 mM) and Ca2+ (e.g. 0.21 mM), there is no inhibition of phosphoenzyme (EP) formation and presteady state Ca2+ translocation, whereas Ca2+-induced conformational changes of the enzyme, and EP decomposition are inhibited. Cleavage of the S-S bond of the cross-links reverses the inhibition of conformational changes but has little effect on the inhibited EP decomposition. This indicates that the inhibition of conformational changes is due to cross-linking, while that of EP decomposition is due to the chemical modification as such. If [Ca2+] is low during the dithiobissuccinimidyl propionate reaction (e.g. pCa 7.6), the Ca2+-induced conformational changes of the enzyme, EP formation, presteady state Ca2+ translocation, and EP decomposition are inhibited, even in the presence of ATP. Cleavage of the cross-links reverses the inhibition of conformational changes and EP formation, but again has little effect on EP decomposition. Thus, the primary effect of cross-linking at high and low [Ca2+] is the inhibition of the Ca2+-induced conformational change, suggesting that extensive interaction of subunits is involved in this reaction step. The fact that EP formation and presteady state Ca2+ translocation are inhibited by cross-linking carried out at low but not at high [Ca2+] suggests that cross-linking takes place at different regions of the enzyme molecule at different [Ca2+].