Transverse Single-Spin Asymmetry for Very Forward Neutral Pion Production in Polarized p+p Collisions at sqrt[s]=510 GeV.

Transverse single-spin asymmetries of very forward neutral pions generated in polarized p+p collisions allow us to understand the production mechanism in terms of perturbative and nonperturbative strong interactions. During 2017, the RHICf Collaboration installed an electromagnetic calorimeter in the zero-degree region of the STAR detector at the Relativistic Heavy Ion Collider (RHIC) and measured neutral pions produced at pseudorapidity larger than 6 in polarized p+p collisions at sqrt[s]=510 GeV. The large nonzero asymmetries increasing both in longitudinal momentum fraction x_{F} and transverse momentum p_{T} have been observed at low transverse momentum p_{T}<1 GeV/c for the first time, at this collision energy. The asymmetries show an approximate x_{F} scaling in the p_{T} region where nonperturbative processes are expected to dominate. A non-negligible contribution from soft processes may be necessary to explain the nonzero neutral pion asymmetries.

Association between excessive supraventricular ectopy and subclinical cerebrovascular disease: a population-based study.

BACKGROUND AND PURPOSE: The association between an increased supraventricular ectopic beat (SVEB) and subclinical cerebrovascular disease remains unclear. Given the emerging concept that an increased SVEB is a marker of atrial cardiomyopathy or atherosclerosis burden, we sought to determine whether excessive supraventricular ectopic activity (ESVEA) is associated with a higher burden of subclinical cerebrovascular disease in the middle-aged to older cohort with neither apparent stroke nor atrial fibrillation. METHODS: We conducted a cross-sectional population-based study of 462 men (mean age, 68.1 years) who underwent 24-h Holter electrocardiography and brain magnetic resonance imaging. ESVEA was defined as the presence of >10 SVEBs/h. Subclinical cerebrovascular diseases were defined as silent brain infarct (SBI), white matter hyperintensity (WMH) and intracranial atherosclerotic stenosis (ICAS). The association of ESVEA with the presence of subclinical cerebrovascular diseases was adjusted for potential confounding covariates. RESULTS: A total of 88 (19.0%) participants had ESVEA and 81 (17.5%), 91 (19.7%) and 109 (23.6%) had SBI, WMH and ICAS, respectively. In multivariable-adjusted Poisson regression with robust error variance, ESVEA was associated with the presence of WMH (relative risk, 1.58; 95% confidence interval, 1.06-2.36) and ICAS (relative risk, 1.49; 95% confidence interval, 1.02-2.18), but not with that of SBI (relative risk, 1.32; 95% confidence interval, 0.86-2.01). These associations were consistent when the graded distributions of subclinical cerebrovascular diseases were applied as outcomes in ordinal logistic regression. CONCLUSIONS: The ESVEA was independently associated with higher burdens of WMH and ICAS. This suggests that increased SVEBs might improve risk stratification of individuals at high risk of subclinical cerebrovascular disease and consequently apparent ischaemic stroke.

Cultural adaptation, content, and protocol of a feasibility study of school-based "Let's learn about emotions" intervention for Finnish primary school children.

Introduction: Emotional awareness and emotion regulation are crucial for cognitive and socio-emotional development in children. School-based interventions on socio-emotional skills have the potential to prevent these problems and promote well-being of children. The Japanese school-based program, Universal Unified Prevention Program for Diverse Disorders (Up2-D2), has shown preventive effects on mental health of children in Japan. The aims of this protocol paper are to describe the unique process of adapting the Up2-D2 from Eastern to Western context, and to present a feasibility study of the intervention, conducted in Finland. Methods: The cultural adaptation process started with the linguistic translation of materials, followed by the modification of language to fit the Finnish context. While the Japanese ideology was saved, some content was adapted to fit Finnish school children. Further modifications were made based on feedback from pupils and teachers. The Finnish version of the program was named "Let's learn about emotions" and consisted of 12 sessions and targeted 8- to 12-year-old pupils. A teacher education plan was established to assist Finnish teachers with the intervention, including a workshop, teachers' manual, brief introductory videos, and online support sessions. A feasibility study involving 512 4th graders in the City of Hyvinkää, South of Finland, was conducted. It assessed emotional and behavioral problems, classroom climate, bullying, loneliness, perception of school environment, knowledge of emotional awareness, and program acceptability. Discussion: The originality of this study underlies in the East-West adaptation of a cognitive behavioral therapy-based program. If promising feasibility findings are replicated in Finland, it could pave the way for further research on implementing such programs in diverse contexts and cultures, promoting coping skills, awareness, social skills and early prevention of child mental health problems. Ethics: The ethical board of the University of Turku gave ethics approval for this research. The educational board of the City of Hyvinkää accepted this study.

Apoptotic protease activating factor 1 (Apaf-1)-independent cell death suppression by Bcl-2.

Reportedly, antiapoptotic Bcl-2 family proteins suppress apoptosis by binding to and inhibiting members of the CED-4 family of caspase activators. To explore this question, we used embryonic stem (ES) cells in which one (-/+) or both (-/-) copies of the gene encoding apoptotic protease activating factor 1 (Apaf-1), a CED-4 homologue, were disrupted by homologous recombination. Stable clones of heterozygous (-/+) and homozygous (-/-) Apaf-1 knockout ES cells that overexpressed Bcl-2 were generated. Withdrawal of serum growth factors or stimulation of heterozygous ES cells with staurosporine (STS), ultraviolet (UV)B irradiation, etoposide (VP16), or cisplatin induced apoptosis followed by cell death (determined by failure to exclude propidium iodide dye). These cell death stimuli also induced activation of several types of caspases and loss of mitochondrial membrane potential (DeltaPsi) in heterozygous (+/-) Apaf-1 knockout ES cells. In addition, overexpression of Bcl-2 protected against these events in Apaf-1-expressing ES cells. In contrast, STS, UVB, and VP16 induced little or no caspase activation and apoptosis in homozygous (-/-) Apaf-1 knockout ES cells. Nevertheless, Apaf-1-deficient ES cells subjected to these cell death stimuli or deprived of growth factors did eventually die through a nonapoptotic mechanism associated with loss of DeltaPsi. Moreover, Bcl-2 overprotection preserved DeltaPsi, reduced the percentage of Apaf-1(-/)- ES cells undergoing cell death, and increased clonigenic survival. The extent of Bcl-2-mediated cytoprotection was not significantly different for heterozygous (-/+) versus homozygous (-/-) Apaf-1 knockout cells. Furthermore, although Bcl-2 could be readily coimmunoprecipitated with Bax, associations with Apaf-1 were undetectable under conditions where Apaf-1 interactions with procaspase-9 were observed. We conclude that Bcl-2 has cytoprotective functions independent of Apaf-1, preserving mitochondrial function through a caspase-independent mechanism.

Relationship between the MRI and EMG measurements.

The purpose of this study was to investigate the effect of intensive eccentric exercise on hamstring muscles by using magnetic resonance imaging (MRI) and to elucidate the relationships between the changes in the electromyographic (EMG) parameters and in the transverse relaxation time (T2) of the hamstring muscles. Seven male volunteers performed eccentric knee flexion exercise, and the EMG activity of the hamstring muscles was simultaneously measured. Before and immediately after the exercise, the maximum isometric knee flexion torque was measured and MR images of the hamstring muscles were obtained. For all hamstring muscles, the EMG activity of the fifth set was significantly lower than that of the first set. For each subject, a significant correlation was detected between the percentage change in the value of the post-exercise T2 value and those of EMG signals during the exercise only for the semitendinosus (ST) muscle and not for the biceps femoris (BF) and the semimembranosus (SM) muscles. These results suggested that the EMG-activity reductions in the BF, ST, and SM muscles were due to neuromuscular fatigue, and moreover the reduction in the ST muscle was due to a failure in the E-C coupling, which was caused by excessive muscle-fiber damage.

Effect of joint position on the electromyographic activity of the semitendinosus muscle.

The semitendinosus (ST) muscle has a tendinous intersection within the muscle belly that separates the ST muscle into distinct proximal and distal compartments. Thus far, no study has compared the electromyographic (EMG) activities between the proximal and distal compartments of the human ST muscle. This study aimed to investigate the intramuscular EMG activity patterns of the proximal and distal compartments of the ST muscle by altering the hip and knee joint positions. The study population comprised eight healthy male volunteers. They performed ramp isometric knee flexion tasks form the relaxed state to the maximal voluntary contraction (MVC) state with (1) the hip and knee at 90 degrees and 0 degrees, respectively (90-0 position), (2) both the hip and knee at 00 (0-0 position), and (3) the hip and knee at 0 degrees and 90 degrees, respectively (0-90 position). Fine-wire electrodes were inserted into the proximal and distal compartments of the ST muscle and the individual EMG activities were recorded. In the 90-0 position, the EMG activity of the distal compartment was higher than that of the proximal compartment at 60%, 80%, and 90% MVC. Moreover, in the 0-90 position, the EMG activity of the proximal compartment was higher than that of the distal compartment at 60% MVC. These results indicated that the lengthened or shortened muscle conditions induced regional differences in the EMG activity patterns, while the two compartments showed equivalent activity when the muscle length was moderate.

Efficacy of dimethyl fumarate in Japanese multiple sclerosis patients: interim analysis of randomized, double-blind APEX study and its open-label extension.

BACKGROUND: Current data for the use of dimethyl fumarate (DMF) in Japanese patients with relapsing-remitting multiple sclerosis (RRMS) is limited. OBJECTIVES: To assess the efficacy of DMF in Japanese patients with RRMS. METHODS: The phase 3, multinational APEX study (ClinicalTrials.gov identifier: NCT01838668) consisted of two parts: a 24-week double-blind part where subjects were randomized to receive DMF 240 mg or placebo twice daily in East Asian and Eastern European countries, and an open-label extension part where all subjects received DMF. The primary endpoint was the total number of new gadolinium-enhancing lesions in Weeks 12-24. In this interim analysis, we report efficacy data in the Japanese subgroup (DMF n = 56; placebo n = 58) over 72 weeks, including an extension phase. RESULTS: DMF reduced the total number of new gadolinium-enhancing lesions in Weeks 12-24 by 85% versus placebo (p < 0.0001). At Week 24, the annualized relapse rate was also reduced by 48% with DMF, versus placebo. DMF reduced the probability of relapse from Week 8 and was sustained. The number of gadolinium-enhancing lesions was maintained through 72 weeks. CONCLUSIONS: DMF demonstrated sustained efficacy in this Japanese subgroup. The results were consistent with those observed in studies of DMF enrolling primarily Caucasian patients.

Presence of immunoglobulin (Ig) M and IgG double isotype-bearing cells and defect of switch recombination in hyper IgM immunodeficiency.

We established a transformed B cell line expressing both IgM and IgG on the cell surface from a patient with hyper IgM immunodeficiency using Epstein-Barr viruses. DNA and RNA of the cells were analyzed. DNA rearrangements of Ig JH gene loci were observed on both chromosomes. Cloning and DNA sequence analyses showed that one has a VHDHJH structure while the other has a DHJH structure. Southern hybridization with 5'-S mu and S gamma region-containing probes indicated germline configuration in the switch regions of mu and gamma genes on both chromosomes. To test expression of mu and gamma chains in the transformed cells at the mRNA-level, we used the polymerase chain reaction with three kinds of synthetic oligonucleotides as primers, one of which was part of the VH gene, while the other two were complementary to parts of C mu and C gamma genes. Sequence analysis of the amplified products showed that the same VHDHJH sequence is directly connected with either the C mu or the C gamma sequence in the mRNAs. This is direct evidence showing that in double isotype-bearing cells one VHDHJH exon in the transcript is alternatively spliced to C mu or C gamma without DNA rearrangement. The defect in this disease could be at the S-S recombination stage.

Predicting skeletal muscle mass from dual-energy X-ray absorptiometry in Japanese prepubertal children.

BACKGROUND/OBJECTIVE: We aimed to develop regression-based prediction equations for estimating total and regional skeletal muscle mass (SMM) from measurements of lean soft tissue mass (LSTM) using dual-energy X-ray absorptiometry (DXA) and investigate the validity of these equations. SUBJECTS/METHODS: In total, 144 healthy Japanese prepubertal children aged 6-12 years were divided into 2 groups: the model development group (62 boys and 38 girls) and the validation group (26 boys and 18 girls). Contiguous MRI images with a 1-cm slice thickness were obtained from the first cervical vertebra to the ankle joints as reference data. The SMM was calculated from the summation of the digitized cross-sectional areas. Total and regional LSTM was measured using DXA. RESULTS: Strong significant correlations were observed between the site-matched SMM (total, arms, trunk and legs) measured by MRI and the LSTM obtained by DXA in the model development group for both boys and girls (R2adj=0.86-0.97, P<0.01, standard error of the estimate (SEE)=0.08-0.44 kg). When these SMM prediction equations were applied to the validation group, the measured total (boys 9.47±2.21 kg; girls 8.18±2.62 kg) and regional SMM were very similar to the predicted values for both boys (total SMM 9.40±2.39 kg) and girls (total SMM 8.17±2.57 kg). The results of the Bland-Altman analysis for the validation group did not indicate any bias for either boys or girls with the exception of the arm region for the girls. CONCLUSIONS: These results suggest that the DXA-derived prediction equations are precise and accurate for the estimation of total and regional SMM in Japanese prepubertal boys and girls.

Plasma phylloquinone, menaquinone-4 and menaquinone-7 levels and coronary artery calcification.

Vitamin K is considered to be involved in the pathological mechanisms of coronary artery calcification (CAC). Correlation between CAC and plasma vitamin K levels was studied. A total of 103 patients, with at least one coronary risk factor, were studied. CAC was measured using 64-slice multislice computed tomography (MSCT) and divided into three groups: none (CAC score = 0; n 25), mild to moderate (0 < CAC score < 400; n 52) and severe (CAC score > 400; n 26). Phylloquinone (PK) and menaquinone (MK)-4 and MK-7 were measured by HPLC-tandem MS. Mean age of patients was 64 (sd 13) years, of which 57 % were male. Median CAC score was 57·2. Median levels of PK, MK-4 and MK-7 were 1·33, 0 and 6·99 ng/ml, showing that MK-7 was the dominant vitamin K in this population. MK-7 showed a significant inverse correlation with uncarboxylated osteocalcin (ucOC, P = 0·014), protein induced by vitamin K absence of antagonist-2 (PIVKA-2, P = 0·013), intact parathyroid hormone (P = 0·007) and bone-specific alkaline phosphatase (P = 0·018). CAC showed an inverse correlation with total circulating uncarboxylated matrix Gla protein (t-ucMGP, P = 0·018) and Hb (P = 0·05), and a positive correlation with age (P < 0·001), creatinine, collagen type 1 cross-linked N-terminal telopeptide (NTX, P = 0·03), pulse wave velocity (P < 0·001) and osteoprotegerin (P < 0·001). However, CAC did not have a significant correlation with plasma levels of PK, MK-4 or MK-7. In conclusion, plasma MK-7, MK-4 or PK level did not show significant correlation with CAC despite the association between plasma vitamin K levels and vitamin K-dependent proteins such as ucOC or PIVKA-2.

Four to seven random casual urine specimens are sufficient to estimate 24-h urinary sodium/potassium ratio in individuals with high blood pressure.

This study was done to clarify the optimal number and type of casual urine specimens required to estimate urinary sodium/potassium (Na/K) ratio in individuals with high blood pressure. A total of 74 individuals with high blood pressure, 43 treated and 31 untreated, were recruited from the Japanese general population. Urinary sodium, potassium and Na/K ratio were measured in both casual urine samples and 7-day 24-h urine samples and then analyzed by correlation and Bland-Altman analyses. Mean Na/K ratio from random casual urine samples on four or more days strongly correlated with the Na/K ratio of 7-day 24-h urine (r=0.80-0.87), which was similar to the correlation between 1 and 2-day 24-h urine and 7-day 24-h urine (r=0.75-0.89). The agreement quality for Na/K ratio of seven random casual urine for estimating the Na/K ratio of 7-day 24-h urine was good (bias: -0.26, limits of agreements: -1.53-1.01), and it was similar to that of 2-day 24-h urine for estimating 7-day 24-h values (bias: 0.07, limits of agreement: -1.03 to 1.18). Stratified analyses comparing individuals using antihypertensive medication and individuals not using antihypertensive medication showed similar results. Correlations of the means of casual urine sodium or potassium concentrations with 7-day 24-h sodium or potassium excretions were relatively weaker than those for Na/K ratio. The mean Na/K ratio of 4-7 random casual urine specimens on different days provides a good substitute for 1-2-day 24-h urinary Na/K ratio for individuals with high blood pressure.

Hypoxic enhancement of type IV collagen secretion accelerates adipose conversion of 3T3-L1 fibroblasts.

Hypoxic modulation of collagen metabolism appears to be related to pathogenesis of many diseases such as fibrosis of connective tissue after injury and scleroderma. Since most of our understanding of how procollagen assembles within the cell has come from studies on cells cultured under normoxia, it may not be helpful for the etiology of the diseases observed in peripheral tissues under hypoxic conditions. As an experimental model for the hypoxic modulation of collagen metabolism, we cultured 3T3-L1 fibroblasts under low partial oxygen pressure and found that hypoxia enhances secretion of type IV collagen 10-fold and accelerates adipose conversion of the cells. The enhanced secretion of type IV collagen was not accompanied by an appreciable increase of alpha1(IV) and alpha2(IV) mRNAs. Prolyl 4-hydroxylase alpha increased only 3-fold under hypoxia. We suggest that hypoxia creates an environment of prolyl 4-hydroxylase alpha(2)beta(2) tetramers favorable for the folding of type IV procollagen which has many interruptions of the Gly-Xaa-Yaa repeat.

The luminosity curve of the protanomalous fovea.

Threshold spectral sensitivities (in the dark, or against bright colored backgrounds) are identical in the red-green range for both protanopes (dichromats) and protanomalous trichromatic color defectives. The latter, however, must have an additional photolabile cone pigment in the red-green range, and its presence is revealed by heterochromatic brightness matching through the spectrum (i.e. luminosity curves). The absorption spectrum of the anomalous cone pigment can be inferred from the protanomalous and protanopic luminosity curve, given reasonable assumptions as to how the different cone mechanisms pool their responses. Depending upon these assumptions, the pigment inferred is either (a) dilute solution of the normal red pigment (assumed density 1.0 for the deuteranope) or (b) similar in its absorption spectrum to the normal green pigment but shifted slightly toward the long wave end of the spectrum. Experimental attempts to choose between these alternatives have so far proved equivocal though (b) seems more likely on the basis of indirect evidence.

The luminosity curve of the deuteranomalous fovea.

Analogous to protans, the two types of deutan color-defectives-the dichromats (deuteranopes) and the anomalous trichromats (deuteranomalous)-do not differ in spectral sensitivity in the red-green range at threshold (either in the dark or against bright colored backgrounds). However, luminosity curves obtained by heterochromatic brightness matching show the latter to be slightly more sensitive in the blue-green, and slightly less so in the red, than the former. Experiment proves that these differences are due (at least in part) to contributions of cones containing the deuteranomalous anomalous pigment which are missing from the deuteranope's eye. The absorption spectrum of the anomalous pigment can be inferred with assumptions (analogous to those already made with protanomalous trichromats) about how the different cone mechanisms pool their responses to yield luminosity. Two alternatives thus revealed are (a) the normal red pigment in dilute solution or (b) a spectrum very similar to that of the normal red pigment but shifted slightly toward the short wave end of the spectrum. Since the spectrum inferred by (a) has the same lambda(max) as the normal red pigment, (a) predicts that deuteranomalous observers will require a negative red primary when matching monochromatic lights of wavelengths near the lambda(max). This is not observed.

Involvement of inhibitory PAS domain protein in neuronal cell death in Parkinson's disease.

Inhibitory PAS domain protein (IPAS), a repressor of hypoxia-inducible factor-dependent transcription under hypoxia, was found to exert pro-apoptotic activity in oxidative stress-induced cell death. However, physiological and pathological processes associated with this activity are not known. Here we show that IPAS is a key molecule involved in neuronal cell death in Parkinson's disease (PD). IPAS was ubiquitinated by Parkin for proteasomal degradation following carbonyl cyanide m-chlorophenyl hydrazone treatment. Phosphorylation of IPAS at Thr12 by PTEN-induced putative kinase 1 (PINK1) was required for ubiquitination to occur. Activation of the PINK1-Parkin pathway attenuated IPAS-dependent apoptosis. IPAS was markedly induced in the midbrain following 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration, and IPAS-deficient mice showed resistance to MPTP-induced degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc). A significant increase in IPAS expression was found in SNpc neurons in patients with sporadic PD. These results indicate a mechanism of neurodegeneration in PD.

The effect of thyroid hormone on fibronectin messenger ribonucleic acid levels in primary cultured rat hepatocytes.

Our previous in vivo studies demonstrated that thyroid hormone promotes the expression of the fibronectin (FN) gene in the rat liver, while it inhibits the synthesis in cultured human skin fibroblasts. These results can be interpreted as either different regulation of FN synthesis or gene expression among tissues, or divergent results of experiments performed in vivo or in vitro. Here we report on the action of thyroid hormone on FN gene expression in vitro using primary cultured hepatocytes compared to that in cultured skin fibroblasts. Hepatocytes were isolated from hypothyroid rats and were cultured in medium supplemented with thyroidectomized bovine serum (TxBS) or fetal bovine serum (FBS). T3 was added 2 or 24 h after plating, and cells were harvested after 2, 6, or 24 h. Total RNA was extracted, and mRNAs for rat FN and albumin were measured. The requirement of de novo protein synthesis for thyroid hormone-mediated induction of FN mRNA was examined by the addition of cycloheximide 15 min before T3 addition. The amount of FN mRNA significantly decreased in the hepatocytes cultured with TxBS compared with those cultured with FBS. The addition of T3 to TxBS resulted in the restoration of FN mRNA to the level in hepatocytes cultured in FBS. FN mRNA increased during the course of culture in the absence of T3; however, a further increase was observed 6 h after T3 addition. The abundance of albumin RNA decreased during the course of culture, but unlike FN mRNA, it was not changed by T3 addition. The increase in FN mRNA by T3 was not influenced by cycloheximide. These results indicate that thyroid hormone enhances FN gene expression in hepatocytes by its direct action without requiring de novo protein synthesis. In contrast, T3 decreased FN mRNA in cultured skin fibroblasts. Thus, the mode of thyroid hormone action on FN gene expression is different among tissues.

Localization of Kex2-like processing endoproteases, furin and PC4, within mouse testis by in situ hybridization.

By in situ hybridization analysis, we show here the localization of furin and PC4, which are both members of a growing family of endoproteases structurally related to the yeast precursor processing protease Kex2, within mouse testis. Furin transcript was detected in both germ and somatic cells, while PC4 transcript was found only in round spermatids. Proenkephalin transcript was also localized in round spermatids. These observations suggest that, within testis, PC4 is involved in processing of peptide precursors such as proenkephalin and may play a role in regulation of sperm maturation, while furin may serve as a more general processing endoprotease.

Immunosuppression by anti-ICAM-1 and anti-LFA-1 monoclonal antibodies of free and vascularized skin allograft rejection.

Immunosuppression by anti-adhesion molecule antibody of free or vascularized skin allograft rejection was investigated in rats. Lewis (LEW, RT11) rats were used as donors and Fisher (F344, RT11v1) rats as the recipients. When F344 rats were treated intraperitoneally (i.p.) with anti-intercellular adhesion molecule-1 (ICAM-1) mAb (1A29) (3 mg/kg/day) and anti-leukocyte function-associated antigen-1 (LFA-1) mAb (WT.1) (3 mg/kg/day) one day prior to grafting and daily after grafting for nine days, free skin graft survival was prolonged only slightly compared with that in control rats which were injected i.p. with a daily dose of 6 mg/kg of anti-TNP mAbs (H1-6-2) one day prior to grafting and daily after grafting for nine days. (Mean survival time [MST] of the free skin graft was 11.2 +/- 0.6 days in the control group and 13.4 +/- 0.3 days in the 1A29 + WT-1 treated group [p < 0.01], respectively.) On the other hand, the vascularized graft survival was prolonged significantly in anti-ICAM-1/LFA-1 mAbs-treated F344 rats as compared with that in control rats. (The mean vascularized graft survival time was 14.2 +/- 0.7 days in the control group and 21.5 +/- 1.9 days in 1A29 + WT-1 treated group [p < 0.002]). Our results suggest that interaction with ICAM-1 and LFA-1 is more important in the rejection of vascularized skin allografts than that of free skin allografts.

Immediate appearance of coronary collaterals during ergonovine-induced arterial spasm.

Angiographically demonstrable collateral flow occurred immediately when coronary arterial spasm was induced by ergonovine in two patients with angina who had organic stenosis of less than 40 percent. These findings suggest that coronary collaterals may develop in response to intermittent brief myocardial ischemia in man, and that collaterals may be preserved even if they are closed at rest and can immediately function when a coronary artery is acutely occluded.

The effect of butoctamide hydrogen succinate on nocturnal sleep: all-night polygraphical studies.

Butoctamide hydrogen succinate (BAHS), related to an organic compound naturally occurring in the central nervous system (CNS), has been shown to increase REM sleep in chronically prepared cats. In the present study, we confirmed that BAHS increases REM sleep in healthy humans, the subjects were six males whose mean age was 21 years and the experiment covered eight consecutive nights. Identical capsules containing either a placebo (linolenic acid) or 600 mg BAHS were administered 1 h prior to recording, which was started at 11 p.m. There was little change in total sleep time, sleep efficiency index, sleep latency, REM sleep latency, or the number of REM sleep periods during the drug- as compared to the baseline periods. There were, however, significant increases in REM sleep and decreases in sleep stages 1 and 2. The night's sleep was divided into three equal portions and analysis of the percentage of sleep stages in each showed that REM sleep markedly increased in the middle third while stages 3 and 4 increased in the last third. A carryover effect of BAHS was recognized during the withdrawal period. The maximum percentage of BAHS-induced REM sleep was 34%. REM density during the drug periods tended to decrease. These results suggest that BAHS may be an efficacious hypnotic in that it increases REM sleep which is suppressed by other clinically used hypnotics.