Previous EST Research Articles

Prevention of post-sphincterotomy bleeding by proton pump inhibitor: A randomized controlled trial.

Post-endoscopic sphincterotomy (EST) bleeding is one of the most frequent complications of endoscopic retrograde cholangiopancreatography (ERCP). Although the use of proton pump inhibitors (PPIs) reduces the risk of peptic ulcer bleeding, their role in preventing EST bleeding has not been evaluated. This study aimed to assess the use of pre-emptive PPIs in patients undergoing EST. This was an investigator-initiated, open-label, randomized study. Consecutive patients scheduled to undergo ERCP and EST were enrolled after excluding those who had previous EST or used acid-suppression agents. Eligible patients were randomized to receive either PPI or standard care. The PPI group received intravenous esomeprazole 4 h before the EST and then every 12 h for 1 day, followed by high-dose oral esomeprazole for 10 days. All patients were followed up for 30 days. The primary outcome was the proportion of patients with combined immediate and delayed overt post-EST bleeding. Altogether 125 patients (60 in the PPI arm and 65 in the standard care arm) who had undergone EST were analyzed. Immediate bleeding was noted in nine (15.0%) patients in the PPI group and four (6.2%) in the standard care group (P = 0.14). Overt delayed post-EST bleeding was seen in two (3.3%) and five (7.7%) patients in PPI and standard care arms, respectively (P = 0.44). There were no significant differences in other outcomes, including a decrease in hemoglobin of >20 g/L, the need for blood transfusion, length of hospital stay and 30-day mortality. Pre-emptive PPI did not reduce the risk of post-EST bleeding.

Translation of mitochondrial swinger RNAs according to tri-, tetra- and pentacodons

Transcriptomes and proteomes include RNA and protein fragments not matching regular transcription/translation. Some ‘non-canonical’ mitochondrial transcripts match mitogenomes after assuming one among 23 systematic exchanges between nucleotides, producing swinger RNAs (nine symmetric, X↔Y, example C↔T; 14 asymmetric, X→Y→Z→X, example A→T→G→A) in GenBank's EST database. Here, reanalyzes of (a) public human mitochondrial transcriptome data (Illumina: RNA-seq) allowed to detect mitochondrial swinger RNAs for all 23 exchanges and (b) independent public human mitochondrial trypsinized proteomic mass spectrometry data allowed to detect peptides predicted from translation of parts of swinger-transformed mitogenomes covered by detected swinger reads. RNA-seq and previous EST swinger transcript data converge. Swinger RNA translation frequently inserts various amino acids at stop codons. Swinger RNA-peptide associations exist also for peptides matching systematically frameshifting translation, peptides entirely coded by tetra- and pentacodons (regular codons expanded by silent mononucleotides at 4th, and silent dinucleotides at 4th and 5th position(s), respectively). Swinger peptides differ from regular mitochondrial proteins: not membrane embedded, reflect warmer, anaerobic, low resource conditions, reminding a free-living ancestor. Tetra- and pentacoded peptides associate with low, high GC contents, respectively, suggesting expanded codon translations associate with thermic stresses. Results confirm experimentally predicted swinger, tetra- and pentacoded mitochondrial peptides, increasing mitogenomic coding density.

The Asian Citrus Psyllid Genome (Diaphorina citri, Hemiptera)

The Asian citrus psyllid, Diaphorina citri (Hemiptera), is an important pest of citrus because it vectors bacteria responsible for huanglongbing, which is one of the most serious diseases of citrus worldwide.  The first genome draft of D. citri (DIACI_1.0) was completed in 2011 (ARS, Ft. Pierce, FL), however, gaps in the assembly prompted additional sequencing using the long run PacBio system at the Los Alamos National Lab, NM.  The revised draft genome (DIACI_1.1) was assembled using the new software PB-Jelly, with an improved N50 of 38 kb (up from 25 kb) and an increase by over 10 million in the number of resolved bases.  The genome and transcriptome have been submitted into the public domain at the National Center for Biotechnology Information, NCBI, and the genome is currently being submitted to be processed and made available for access by the larger research community [http://www.ncbi.nlm.nih.gov/genome?LinkName=bioproject_genome&from_uid=29447].  The psyllid transcriptome identified over 25,600 predicted genes, and is supported by an additional 19,598 previous EST’s.  Life-stage specific transcripts were identified for adults, nymphs and eggs.  BlastX analyses showed that the psyllid genome has the most similarity to the Pea Aphid, Acyrthosiphon pisum, another hemipteran.  The transcriptome data was provided to the Innocentive® Challenge Program in 2011 to advance efforts for RNAi development against psyllids.  Other researchers are also using these data to develop strategies to suppress psyllid populations.  Efforts are now focused on annotation of the psyllid genome which will provide more information on the genetic basis of psyllid biology.  Free Downloads of the most recent datasets can be found at: http://www.psyllid.org/node/10 which includes the transcriptome and predicted protein files in FASTA format, and the gene locations on the DIACI_1.1 Genome assembly (GFF3 format).

The pineapple AcMADS1 promoter confers high level expression in tomato and Arabidopsis flowering and fruiting tissues, but AcMADS1 does not complement the tomato LeMADS-RIN (rin) mutant.

A previous EST study identified a MADS box transcription factor coding sequence, AcMADS1, that is strongly induced during non-climacteric pineapple fruit ripening. Phylogenetic analyses place the AcMADS1 protein in the same superclade as LeMADS-RIN, a master regulator of fruit ripening upstream of ethylene in climacteric tomato. LeMADS-RIN has been proposed to be a global ripening regulator shared among climacteric and non-climacteric species, although few functional homologs of LeMADS-RIN have been identified in non-climacteric species. AcMADS1 shares 67 % protein sequence similarity and a similar expression pattern in ripening fruits as LeMADS-RIN. However, in this study AcMADS1 was not able to complement the tomato rin mutant phenotype, indicating AcMADS1 may not be a functionally conserved homolog of LeMADS-RIN or has sufficiently diverged to be unable to act in the context of the tomato network of interacting proteins. The AcMADS1 promoter directed strong expression of the GUS reporter gene to fruits and developing floral organs in tomato and Arabidopsis thaliana, suggesting AcMADS1 may play a role in flower development as well as fruitlet ripening. The AcMADS1 promoter provides a useful molecular tool for directing transgene expression, particularly where up-regulation in developing flowers and fruits is desirable.

Genes responding to water deficit in apple (Malus × domestica Borkh.) roots.

BackgroundIndividual plants adapt to their immediate environment using a combination of biochemical, morphological and life cycle strategies. Because woody plants are long-lived perennials, they cannot rely on annual life cycle strategies alone to survive abiotic stresses. In this study we used suppression subtractive hybridization to identify genes both up- and down-regulated in roots during water deficit treatment and recovery. In addition we followed the expression of select genes in the roots, leaves, bark and xylem of ‘Royal Gala’ apple subjected to a simulated drought and subsequent recovery.ResultsIn agreement with studies from both herbaceous and woody plants, a number of common drought-responsive genes were identified, as well as a few not previously reported. Three genes were selected for more in depth analysis: a high affinity nitrate transporter (MdNRT2.4), a mitochondrial outer membrane translocase (MdTOM7.1), and a gene encoding an NPR1 homolog (MpNPR1-2). Quantitative expression of these genes in apple roots, bark and leaves was consistent with their roles in nutrition and defense.ConclusionsAdditional genes from apple roots responding to drought were identified using suppression subtraction hybridization compared to a previous EST analysis from the same organ. Genes up- and down-regulated during drought recovery in roots were also identified. Elevated levels of a high affinity nitrate transporter were found in roots suggesting that nitrogen uptake shifted from low affinity transport due to the predicted reduction in nitrate concentration in drought-treated roots. Suppression of a NPR1 gene in leaves of drought-treated apple trees may explain in part the increased disease susceptibility of trees subjected to dehydrative conditions.

Custom Microarray Analysis for Transcript Profiling of Dormant Vegetative Buds of Japanese Apricot during Prolonged Chilling Exposure

Bud dormancy is a critical developmental process for perennial plant survival, and also an important physiological phase that affects the next season’s growth of temperate fruit trees. Bud dormancy is regulated by multiple genetic factors, and affected by various environmental factors, tree age and vigor. To understand the molecular mechanism of bud dormancy in Japanese apricot (Prunus mume Sieb. et Zucc.), we constructed a custom oligo DNA microarray covering the Japanese apricot dormant bud ESTs referring to the peach (P. persica) genome sequence. Because endodormancy release is a chilling temperature-dependent physiological event, genes showing chilling-mediated differential expression patterns are candidates to control endodormancy release. Using the microarray constructed in this study, we monitored gene expression changes of dormant vegetative buds of Japanese apricot during prolonged artificial chilling exposure. In addition, we analyzed seasonal gene expression changes. Among the 58539 different unigene probes, 2345 and 1059 genes were identified as being more than twofold up-regulated and down-regulated, respectively, following chilling exposure for 60 days (P < 0.05). Cluster analysis suggested that the expression of the genes showing expression changes by artificial chilling exposure were coordinately regulated by seasonal changes. The down-regulated genes included P. mume DORMANCY-ASSOCIATED MADS-box genes, which supported previous quantitative RT-PCR and EST analyses showing that these genes are repressed by prolonged chilling exposure. The genes encoding lipoxygenase were markedly up-regulated by prolonged chilling. Our parametric analysis of gene-set enrichment suggested that genes related to jasmonic acid (JA) and oxylipin biosynthesis and metabolic processes were significantly up-regulated by prolonged chilling, whereas genes related to circadian rhythm were significantly down-regulated. The results obtained from microarray analyses were verified by quantitative RT-PCR analysis of selected genes. Taken together, we have concluded that the microarray platform constructed in this study is applicable for deeper understanding of the molecular network related to agronomically important bud physiology, including dormancy release.

Cloning and expression of apyrase gene from Ancylostoma caninum in Escherechia coli.

Apyrase encoding metal-ions activated plasma membrane protease is present in animal and plant tissues. This enzyme can hydrolyze ADP and ATP pyrophosphate bond, resulting in AMP and free phosphate groups, and plays an important role for insects and parasites to evade host immune system. However localization and function of apyrase in the canine hookworm, Ancylostoma caninum, remains unknown. To analyze apyrase gene in A. caninum (a eukaryotic parasitic hookworm), a pair of primers was designed according to the previous EST data. The full-length cDNA of apyrase gene was amplified from A. caninum by RT-PCR. The partial cDNA of apyrase encodes 249 amino acid protein was expressed in Escherechia coli. The recombinant protein was induced to express under proper conditions and the molecular size was as expected. The recombinant protein was purified. The transcripts of apyrase in different stages of A. caninum were analyzed by the Real-time PCR assay, and Immuno-localization assays were used to research the protein expression in different stages of A. caninum.

Characterization of genes with a putative key role in the parasitic lifestyle of the nematode Strongyloides ratti

Parasitic nematodes are significant pathogens of humans and other animals. The molecular and genetic basis of animal parasitism is not yet fully understood. Strongyloides spp. are a genus of gastrointestinal nematodes of which species infect approximately 100–200 million people worldwide. S. ratti is a natural parasite of the rat, and a useful and amenable laboratory model. Previous EST and microarray analyses of the S. ratti life cycle have identified genes whose expression was specific, or biased, to the parasitic adult stage, suggesting that they may play a key role in parasitism in this species. Here we have further investigated the expression of these genes (by RT-PCR) throughout the S. ratti life-cycle. We produced recombinant proteins in vitro for a subset of these genes, which were used in Western blot analyses to investigate the distribution of the gene products among different stages of the S. ratti life cycle. We tested the efficacy of these recombinant proteins as anti-S. ratti vaccines. One of the proteins was detected in the excretory/secretory products of the parasitic stages.

Deep sequencing of the Camellia sinensis transcriptome revealed candidate genes for major metabolic pathways of tea-specific compounds

BackgroundTea is one of the most popular non-alcoholic beverages worldwide. However, the tea plant, Camellia sinensis, is difficult to culture in vitro, to transform, and has a large genome, rendering little genomic information available. Recent advances in large-scale RNA sequencing (RNA-seq) provide a fast, cost-effective, and reliable approach to generate large expression datasets for functional genomic analysis, which is especially suitable for non-model species with un-sequenced genomes.ResultsUsing high-throughput Illumina RNA-seq, the transcriptome from poly (A)+ RNA of C. sinensis was analyzed at an unprecedented depth (2.59 gigabase pairs). Approximate 34.5 million reads were obtained, trimmed, and assembled into 127,094 unigenes, with an average length of 355 bp and an N50 of 506 bp, which consisted of 788 contig clusters and 126,306 singletons. This number of unigenes was 10-fold higher than existing C. sinensis sequences deposited in GenBank (as of August 2010). Sequence similarity analyses against six public databases (Uniprot, NR and COGs at NCBI, Pfam, InterPro and KEGG) found 55,088 unigenes that could be annotated with gene descriptions, conserved protein domains, or gene ontology terms. Some of the unigenes were assigned to putative metabolic pathways. Targeted searches using these annotations identified the majority of genes associated with several primary metabolic pathways and natural product pathways that are important to tea quality, such as flavonoid, theanine and caffeine biosynthesis pathways. Novel candidate genes of these secondary pathways were discovered. Comparisons with four previously prepared cDNA libraries revealed that this transcriptome dataset has both a high degree of consistency with previous EST data and an approximate 20 times increase in coverage. Thirteen unigenes related to theanine and flavonoid synthesis were validated. Their expression patterns in different organs of the tea plant were analyzed by RT-PCR and quantitative real time PCR (qRT-PCR).ConclusionsAn extensive transcriptome dataset has been obtained from the deep sequencing of tea plant. The coverage of the transcriptome is comprehensive enough to discover all known genes of several major metabolic pathways. This transcriptome dataset can serve as an important public information platform for gene expression, genomics, and functional genomic studies in C. sinensis.

Sex versus parthenogenesis: A transcriptomic approach of photoperiod response in the model aphid Acyrthosiphon pisum (Hemiptera: Aphididae)

Most aphids develop a cyclic parthenogenesis life-cycle. After several generations of viviparous parthenogenetic females, it follows a single annual generation of sexual individuals, usually in autumn, that mate and lay the sexual eggs. Shortening of photoperiod at the end of the summer is a key factor inducing the sexual response. With the survey here reported we aimed at identifying a collection of candidate genes to participate at some point in the cascade of events that lead to the sexual phenotypes. Following a suppression subtractive hybridization methodology (SSH) on the model aphid Acyrthosiphon pisum, we built and characterised two reciprocal cDNA libraries (SDU and SDD) enriched respectively in genes up-regulated or down-regulated by short photoperiod conditions that lead to the sexual response in this aphid species. A total of 557 ESTs were obtained altogether representing 223 non-overlapping contigs. 29% of these were new sequences not present in previous aphid EST libraries. BLAST searches allowed putative identification of about 54% of the contigs present in both libraries. Relative quantification of expression through real-time quantitative PCR demonstrated the differential expression in relation with the photoperiod of 6 genes (3 up-regulated and 3 down-regulated by shortening the day length). Among these, expression of a tubulin gene, two cuticular proteins and a yet unidentified sequence along the day–night cycle was further investigated. Implications for current studies on gene regulation of the dichotomy sex vs. parthenogenesis in aphids are discussed.

Causes and complications of multiple repeated endoscopic sphincterotomies

There is little information on the background of repeated endoscopic sphincterotomies (re-EST). We have examined frequency and background of complications of re-EST in our tertiary endoscopic center. Patients and method: Between 1999 and 2004, we retrospectively investigated the medical records of patients who underwent endoscopic retrograde choledocho-pancreatography (ERCP) with several (two or more) re-EST-s. Results: During the 6 years there were 6504 ERCPs including 1689 cases of EST and 266 cases of re-EST with the following etiologies: adenoma of the papilla: 34.2%, choledocholithiasis: 28.2%, chronic calcifying pancreatitis: 12.0%, previous incomplete EST: 5.6%, papillitis: 3.1%, acute pancreatitis: 2.6%, pancreatic tumor: 2.6%, gallbladder tumor: 1.9%, papillary sclerosis: 1.5%, choledochus tumor: 1.5%, tumor of the papilla: 0.8%. The number of patients who repeatedly (twice or more) underwent re-EST was 29. In these cases re-EST was performed 76 times (with an average of 2.6 per patient). The most frequent reasons for re-EST were: choledocholithiasis: 33 (43.2%), papillary adenoma: 29 (38.2%), papilla restenosis of unknown origin: 9 (11.8%), cholangitis: 6 (7.9%), juxtapapillary diverticla: 5 (6.6%), previous incomplete EST: 4 (5.3%), papillary sclerosis: 4 (5.3%), chronic calcifying pancreatitis: 2 (2.6%), choledochus stricture: 2 (2.6%), mucin producing neo plasma: 2 (2.6%), pancreatic carcinoma: 2 (2.6%), papillitis: 2 (2.6%) and acute pancreatitis: 1 (1.3%) The following complications were found in 25% of all re-EST-s bleeding (no transfusion required): 8 (10.5%), cholangitis: 7 (9.2%), pancreatitis: 2 (2.6%), hepatic abscess: 1 (1.3%), choledochus stricture: 1 (1.3%). Summary: In the examined population of patients (including difficult cases of several hospitals) re-EST was required mostly in cases of choledocholithiasis, adenoma of the papilla and restenosis of unkown origin. Most frequent complications were minor bleedings, cholangitis and pancreatitis. A sufficient length of the primary sphincterotomy probably prevents restenosis of the papilla.

Gene discovery and annotation using LCM-454 transcriptome sequencing

454 DNA sequencing technology achieves significant throughput relative to traditional approaches. More than 261,000 ESTs were generated by 454 Life Sciences from cDNA isolated using laser capture microdissection (LCM) from the developmentally important shoot apical meristem (SAM) of maize (Zea mays L.). This single sequencing run annotated >25,000 maize genomic sequences and also captured approximately 400 expressed transcripts for which homologous sequences have not yet been identified in other species. Approximately 70% of the ESTs generated in this study had not been captured during a previous EST project conducted using a cDNA library constructed from hand-dissected apex tissue that is highly enriched for SAMs. In addition, at least 30% of the 454-ESTs do not align to any of the approximately 648,000 extant maize ESTs using conservative alignment criteria. These results indicate that the combination of LCM and the deep sequencing possible with 454 technology enriches for SAM transcripts not present in current EST collections. RT-PCR was used to validate the expression of 27 genes whose expression had been detected in the SAM via LCM-454 technology, but that lacked orthologs in GenBank. Significantly, transcripts from approximately 74% (20/27) of these validated SAM-expressed "orphans" were not detected in meristem-rich immature ears. We conclude that the coupling of LCM and 454 sequencing technologies facilitates the discovery of rare, possibly cell-type-specific transcripts.

The proteome of the phytopathogenic fungusSclerotinia sclerotiorum

In order to gain a more thorough understanding of the phytopathogenic fungus, Sclerotinia sclerotiorum, we initiated a proteome-level study of the fungal mycelia and secretome. To our knowledge, this is the first comprehensive proteome-level study of this fungus. Extracted mycelial proteins and secreted proteins collected from liquid culture were separated using 2-DE and annotated following ESI-q-TOF MS/MS. Fifty-two secreted proteins were reproducibly present in three biological replicates and 18 of them were identified by MS/MS while over 200 mycelial proteins were reproducibly present in three independent extractions and approximately half of them were identified. Many of the annotated secreted proteins were cell wall degrading enzymes that had been previously identified as pathogenicity or virulence factors of S. sclerotiorum; however, the contribution to the virulence of S. sclerotiorum of one of the identified proteins, alpha-L-arabinofuranosidase, is yet to be analyzed. Furthermore, previous comprehensive EST studies did not detect the presence of the alpha-L-arabinofuranosidase transcript, which demonstrates the merit of performing proteome-level research. All of the secreted and mycelial proteins identified were functionally classified, and the known and proposed roles in disease initiation or progression for many of them are discussed.

Isolation, sequence analysis, and expression studies of florally expressed cDNAs in Arabidopsis

Molecular genetics has identified dozens of genes that regulate flower development in Arabidopsis. However, the complexity of flower development suggests that many other genes are yet to be uncovered. To identify floral genes that are expressed at low levels in the flower, we have sequenced 1587 cDNA fragments from a subtractive floral cDNA library. A total of 1222 unique genes represented by these ESTs are distributed on all five chromosomes with similar frequencies as all predicted genes in the genome. Among these, 17 genes were shown to be expressed anywhere for the first time because they were not found in previous EST and full-length cDNA datasets. Furthermore, 724 of the genes revealed by this library were not definitively shown to be expressed in the flower by previous floral EST datasets. In addition, 49 transcriptional regulators, 31 protein kinases, 12 zinc-finger proteins and other signaling proteins were found to be present in floral buds. Moreover, the EST sequences likely extended the transcribed regions of 26 previously annotated genes, and may have uncovered several previously unrecognized genes. To obtain additional clues about possible gene function, we hybridized cDNA microarray with probes derived from wild-type Arabidopsis rosette leaves and floral buds. We estimated that over 50% of genes were expressed at levels lower than 1/30 of the highest detectable signal intensity, indicating that many floral genes are expressed at low levels. Furthermore, 97 genes were found to be expressed at a higher level in the flower than the leaf by the Significance Analysis of Microarray (SAM) method with a 1.0% false discovery rate (FDR). Further RT-PCR analyses of selected genes support the microarray results. We suggest that the genes encoding putative regulatory proteins and at least some proteins with currently unknown functions might play important roles during flowering.

Physical mapping of the CA6, ENO1, and SLC2A5 (GLUT5) genes and reassignment of SLC2A5 to 1p36.2

Several human malignancies frequently exhibit deletions or rearrangements of the distal short arm of chromosome 1 (1p36), and a number of genetic diseases also map to this region. The carbonic anhydrase (CA6) and α-enolase (ENO1) genes, previously mapped to 1p36, were physically linked in yeast- and P1-artificial chromosome (YAC and PAC) contigs. PACs from the contig were mapped to 1p36.2 by fluorescence in situ hybridization. The ESTs D1S2068, D1S274E, D1S3275, and stSG4370 were also placed in the same contig. The physical map was integrated with the genetic map of chromosome 1 by assignment of genetic markers D1S160, D1S1615, and D1S503 to the contig. Sequencing of the EST clone representing D1S274E indicated that it was derived from the same transcript as D1S2068E and corresponded to the SLC2A5 (GLUT5) gene, previously assigned to 1p31. Reassignment of SLC2A5 to 1p36.2 was confirmed by somatic cell and radiation hybrid mapping panels and was consistent with previous EST mapping data. Sequencing of the EST clone for D1S274E revealed the presence of intronic sequences, suggesting that the clone was derived from an unprocessed message. The presence of unprocessed and/or alternatively spliced EST clones has potential ramifications for EST-based genomic projects. This information should facilitate the mapping of tumor suppressor and genetic disease loci that have been localized to this region.

Drug variables in the etiology of tardive dyskinesia application of discriminant function analysis

1. 1. From the medical records of 50 chronic, hospitalized, psychotic patients, information was obtained on numerous drug and non-drug variables. 2. 2. On the basis of the Simpson Tardive Dyskinesia Rating Scale, the study sample was dichotomized into dyskinesia (N = 23) and no dyskinesia (N = 27) groups. 3. 3. A step-wise multiple discriminant function analysis showed the following variables to discriminate significantly between the two groups: 1) duration of low potency neuroleptic therapy; 2) previous EST; 3) length of neuroleptic therapy; 4) total amount of long-acting fluphenazine; and 5) abnormal EEG. 4. 4. The equation correctly classified 85.2% of “no dyskinesia” and 60.9% of “dyskinesia” patients. 5. 5. The discriminant function analysis appears to be a useful tool in disentangling the relative importance of overlapping etiological factors in dyskinesia.

Clinical and statistical evaluation of results with plegicil AY-57062 in chronic mental patients.

Acepromazine was tried in 48 chronic mental patients, 12 male and 36 female. Their ages ranged from 22 to 61 years, and the time elapsed from their first admission in a mental hospital ranged from 1 to 29 years. The majority of the patients were suffering from various types of schizophrenic reactions, and no significant number of other diagnostic categories was included. Acepromazine was administered orally for an average of 16 weeks. The highest daily dosage reached 120 mg., with an average of 99.58 mg. The drug did improve symptoms and behavior in a significant manner. Thirty-seven out of the 48 patients showed some improvement; 7 showed no change; 1 patient worsened. The other 3 patients worsened and developed toxic reactions; the medication was discontinued and the patients were removed from the study. There was a slight indication that younger patients and those admitted recently were helped more than older patients or those whose first admission was many years ago. There was no significant difference in the effect of acepromazine on various diagnostic categories. There was no relation between the total length of the medication and the degree of improvement. There was a slight but not significant indication that a slower increment in dosage results in greater improvement than a faster increment. Two main areas, Psychotic Symptoms and Behavioral Traits, improved more than Intellectual Resources, Character Traits and Interpersonal Relationships, and Socialization and Rehabilitation, but the improvement in Behavioral Traits is not significantly correlated with the improvement in the Psychotic Symptoms. With the exception of 3 patients for whom the drug had to be discontinued because of toxic reaction characterized by extreme agitation, confusion and weakness, very few side effects have occurred and none was serious. No jaundice or allergic reactions were noted, and a very low incidence of Parkinsonism was encountered. No relation was found between the number or the type of the side effects, including Parkinsonism, and the degree of improvement. Finally, it was noted that in this series of patients, acepromazine proved effective where other drugs or EST were not and that of the 7 patients who showed no improvement on acepromazine, none had improved on previous chemotherapy or EST.