Expansion of the basic knowledge on the inheritance of characters that allow the development of new maize breeding techniques / Expansión de los conocimientos básicos de la herencia de caracteres que posibiliten desarrollar nuevas técnicas de mejoramiento en maíz

ABSTRACT In order to increase the efficiency of maize hybrid seed production it is necessary to achieve a high grain yield to reduce production costs. This goal requires an expansion of the basic knowledge of the inheritance of characters in order to develop new breeding techniques to improve experimental materials with hard endosperm (flint). The balanced lethal system allows to study the relative contribution of different chromosome segments to hybrid vigour due to the heterozygosity of certain chromosome segments while the rest of the genome becomes homocygotic through continuous selfing. In this way, these segments can be transferred to inbred lines in order to increase grain yield or tassel size (to increase pollen production). The goal of this study was to transfer a heterotic segment by using a balanced lethal system regulated line (BLS14), through crosses and backcrosses, to S5 flint lines derived from two commercial hybrids, ACA 2000 and Cóndor with closed pedigree, with the objective of increase grain yield or tassel size for pollen production. The analysis of variance (ANOVA) and principal components analysis (PCA) showed a significant improvement in grain yield and tassel size in the S5 flint lines of both commercial hybrids, carrying the heterotic segment of the BLS14 line.

RESUMEN Para incrementar la eficiencia en la producción de semillas híbridas en maíz se necesitan altos rendimientos con un correlativo bajo costo de producción. Esto requiere una expansión de los conocimientos básicos de la herencia de caracteres que posibiliten desarrollar nuevas técnicas de mejoramiento sobre materiales experimentales de textura dura (flint). Los sistemas de letales balanceados permiten estudiar la contribución relativa de distintos segmentos heteróticos en el vigor híbrido dado que permiten lograr la heterocigosis cuasipermanente de una porción del genomio, mientras el resto del genoma se vuelve homocigota por autofecundaciones sucesivas. Estos sistemas pueden ser transferidos a líneas endocriadas para incrementar el rendimiento del grano y el tamaño de la panoja para aumentar la producción de polen. El objetivo de este trabajo fue incorporar un segmento heterótico de una línea regulada por un sistema de letales balanceados (BLS14), mediante cruzamiento y retrocruza, a líneas S5 derivadas de dos híbridos comerciales, ACA 2000 y Cóndor, de pedigree cerrado, con textura dura (flint), con la finalidad de aumentar el rendimiento en grano o el tamaño de la panoja para la producción de polen. Los análisis de variancia (ANOVA) y de componentes principales (ACP) mostraron un incremento significativo en el rendimiento del grano y el tamaño de la panoja de las líneas S5 de ambos híbridos comerciales, portando cada una de ellas el segmento heterótico proveniente de la línea BLS14.

[Impact of laparoscopic sacrocolpopexy, with or without a midurethral sling, on lower urinary tract symptoms]. / Impact de la promonto-fixation cœlioscopique, avec ou sans bandelette sous-urétrale, sur les symptômes du bas appareil urinaire.

OBJECTIVE: To evaluate the impact of laparoscopic sacrocolpopexy, with or without simultaneous midurethral sling (MUS), on urinary symptoms and health-related quality of life of patients. MATERIALS: A prospective analysis was carried out including 83 women with symptomatic pelvic organ prolapse who had laparoscopic sacrocolpopexy between 2009 and 2011. Patients were classified according to the preoperative clinical examination (stress test). Thirty patients with patent (group A) stress urinary incontinence (SUI) and 15 patients with occult SUI (group B) had a MUS associated with sacrocolpopexy. Thirty-eight patients with negative stress test (group C) were treated by sacrocolpopexy without MUS, even if they had history of SUI. At each visit, urinary symptoms (UDI-6) and their impact on quality of life (UIQ-7) were evaluated using validated self-questionnaires, Pelvic Floor Distress Inventory and Pelvic Floor Impact Questionnaire. RESULTS: After 3years of mean follow-up, SUI was improved in 22/30 (77%) of patients in group A and only one patient needed a second MUS. Dysuria was cured in 9/12 (75%), 5/7 (71%) and 16/19 (84%) of patients of groups A, B, C respectively and urge urinary incontinence in 13/19 (68%), 2/2 (100%) and 4/6 (67%) of patients. The rate of de novo urge incontinence was respectively 1/11 (9%), 2/13 (15%) and 6/32 (19%). De novo SUI appeared in 6/32 (19%) of patients in group C, but only 2 of them secondarily needed a MUS. After 3 years, our study showed a significant decrease of UDI-6 of 62, 63 and 48% comparing with preoperative score and of UIQ-7 of 77, 54 and 81%. CONCLUSION: Laparoscopic sacrocolpopexy associated with MUS for patent stress urinary incontinence improves significantly stress and urgency urinary incontinence. Laparoscopic sacrocolpopexy without MUS, when physical exam shows a negative stress test, significantly reduces voiding difficulties with very few cases of de novo stress and urge incontinence. LEVEL OF EVIDENCE: 4.

The C331A mutant of neuronal nitric-oxide synthase is defective in arginine binding.

It has been proposed that Cys99 of human endothelial nitric oxide synthase (eNOS) is responsible for tetrahydrobiopterin (BH4) binding. To examine this possibility rigorously, we expressed rat neuronal NOS (nNOS) in Escherichia coli, with the homologous Cys331 to Ala mutation, and characterized structural and functional attributes of the purified, mutated enzyme. C331A-nNOS, as isolated, was catalytically incompetent. Upon prolonged incubation with L-arginine (L-Arg), not only BH4 binding but also catalytic activity could be restored. In contrast to wild-type nNOS (WT-nNOS), which exhibits an absorbance maximum at 407 nm that shifts immediately upon L-arginine addition to a high spin form, the C331A-nNOS mutant, as isolated, exhibited an absorbance maximum at 420 nm. C331A-nNOS, as isolated, did not bind detectable levels of either [3H]Nomega-nitro-L-arginine or [3H]BH4, but [3H]BH4 binding was reinstated after extended incubation with excess L-arginine. On the other hand, C331A-nNOS and WT-NOS were identical with regard to imidazole binding affinity, CaM binding affinity, and rates of cytochrome c and 2, 6-dichlorophenolindophenol reduction. EPR spectroscopy revealed conversion of low to high spin heme after extended incubation with high concentrations of L-arginine (0.1-10 mM). The estimated Kd for L-arginine binding to C331A-nNOS was two orders of magnitude greater than WT-nNOS (>100 microM versus 2-3 microM). Here we propose that Cys331 plays an important role in stabilizing L-arginine binding to nNOS. Our findings suggest that the primary dysfunction in the C331A mutant of nNOS, as isolated, is disruption of the BH4-substrate binding interactions as broadcast from this mutated cysteine residue. Prolonged incubation with L-arginine appears to cause remodeling of the mutant protein to a form similar to that of WT-nNOS, allowing for normalized BH4 binding and nitric oxide synthetic activity.

Lower lipid peroxide levels in practitioners of the Transcendental Meditation program.

OBJECTIVE: Oxidative stress or free radical activity may contribute to the pathophysiology of atherosclerosis and other chronic diseases associated with aging. Because psychosocial stress has been shown to increase oxidative stress, we conducted an exploratory study to investigate the effects of stress reduction with the Transcendental Meditation program on serum lipid peroxide levels in elderly subjects. METHOD: Forty-one normally healthy subjects (aged 56 to 74 years, average 67 years) were recruited from the same Midwest city. Eighteen were long-term practitioners of the TM program (average 16.5 years). Twenty-three controls were not practicing a formal stress management technique. Venous blood samples were analyzed for lipid peroxides by the TBARS assay. A dietary questionnaire was used to assess fat intake, red meat consumption, antioxidant vitamin supplementation, and smoking. Differences between groups and subgroups were analyzed by t test, and correlations. RESULTS: Significantly lower serum levels of lipid peroxides were found in the TM practitioners compared with controls (-15%, p = .026). No significant differences were found between groups on smoking, fat intake, or vitamin supplementation. TM practitioners also had lower red meat consumption but matched subgroup analysis and partial correlations did not confirm a relationship between red meat intake and lipid peroxide levels. CONCLUSIONS: These preliminary findings suggest that lower serum lipid peroxide levels may be associated with stress reduction using the Transcendental Meditation technique. Prospective controlled trials are needed to confirm that this effect is because of TM practice rather than other lifestyle factors, such as diet.

An autoinhibitory control element defines calcium-regulated isoforms of nitric oxide synthase.

Nitric oxide synthases (NOSs) are classified functionally, based on whether calmodulin binding is Ca2+-dependent (cNOS) or Ca2+-independent (iNOS). This key dichotomy has not been defined at the molecular level. Here we show that cNOS isoforms contain a unique polypeptide insert in their FMN binding domains which is not shared with iNOS or other related flavoproteins. Previously identified autoinhibitory domains in calmodulin-regulated enzymes raise the possibility that the polypeptide insert is the autoinhibitory domain of cNOSs. Consistent with this possibility, three-dimensional molecular modeling suggested that the insert originates from a site immediately adjacent to the calmodulin binding sequence. Synthetic peptides derived from the 45-amino acid insert of endothelial NOS were found to potently inhibit binding of calmodulin and activation of cNOS isoforms. This inhibition was associated with peptide binding to NOS, rather than free calmodulin, and inhibition could be reversed by increasing calmodulin concentration. In contrast, insert-derived peptides did not interfere with the arginine site of cNOS, as assessed from [3H]NG-nitro-L-arginine binding, nor did they potently effect iNOS activity. Limited proteolysis studies showed that calmodulin's ability to gate electron flow through cNOSs is associated with displacement of the insert polypeptide; this is the first specific calmodulin-induced change in NOS conformation to be identified. Together, our findings strongly suggest that the insert is an autoinhibitory control element, docking with a site on cNOSs which impedes calmodulin binding and enzymatic activation. The autoinhibitory control element molecularly defines cNOSs and offers a unique target for developing novel NOS activators and inhibitors.

Structural analysis of the Trichodesmium nitrogenase iron protein: implications for aerobic nitrogen fixation activity.

Trichodesmium spp. are marine filamentous nitrogen-fixing cyanobacteria which play an important role in the nitrogen budget of the open ocean. Trichodesmium is unique in that it is nonheterocystous and fixes nitrogen during the day, while evolving oxygen through photosynthesis, even though nitrogenase is sensitive to oxygen inactivation. The sequence of the gene encoding the Fe protein component of nitrogenase from the recently cultivated isolate Trichodesmium sp. IMS 101 was used to construct a 3-dimensional model of the Fe protein, by comparison to the X-ray crystallographic structure of the Fe protein of the gamma-proteobacterium Azotobacter vinelandii. The primary differences in amino acid sequences of the Fe protein from diverse organisms do not impact the critical structural features of the Fe protein. It can be concluded that aerobic nitrogen fixation in Trichodesmium spp. is not facilitated by unique structural features of Trichodesmium Fe protein.

Modular structure of neuronal nitric oxide synthase: localization of the arginine binding site and modulation by pterin.

A putative dihydrofolate reductase (DHFR) module has been identified in neuronal nitric oxide synthase, consisting of amino acids 558-721, and is proposed to be the site of tetrahydrobiopterin (BH4) binding. This polypeptide has been expressed in E. coli as a fusion protein with glutathione S-transferase (GST), using the plasmid pGEX-4T1. The protein binds N omega-nitro-L-arginine (NNA) tightly, but this binding is not stimulated by BH4. cDNAs for Module II (residues 220-557) and Module III (residues 220-721) have been expressed as fusion proteins with GST. Module II does not bind NNA. However, Module III does bind NNA and binding is significantly stimulated by BH4. These observations are taken as strong evidence that the DHFR module contains the L-arginine binding site and, presumably, the BH4 binding site by analogy to its homology with DHFR, but that tight binding of BH4 requires amino acids 220-577.

Further studies on the "de novo" process of alpha 1,4-alpha 1,6 glucopolysaccharides--corn starch biogenesis.

Starch biogenesis in corn endosperm from Flint, Sugary, Waxy, as a function of the grain filling/period was studied. We have differentially identified the initiation from the elongation process. After incubating under unprimed conditions, two glucose radiolabelled protein bands of 39,5 and 36 kDa were obtained. UDP(14C)Glc was the preferred glucosyl donor but also ADP(14C)Glc was. It was additionally found that more than one glucose was transferred to the protein or to the alpha 1,4-glucan linked to protein from UDPGlc. These results were supported by the fact that the glucosylated protein from UDPGlc liberates maltooligosaccharides after alpha- or beta-amylase treatment. The elongation activity in the first steps related to the glucan linked to protein is different from starch synthase. Therefore, we are proposing a model for starch biogenesis where two new transglucosylating enzyme activities are necessary to prepare the primer for starch synthase.

Factors that predict spontaneous remission of ectopic atrial tachycardia.

Ectopic atrial tachycardia (EAT) is usually considered as benign and easy to treat. The natural history of the disease, however, has not yet been clarified. The purpose of the study was to analyse its spontaneous evolution in a cohort of EAT patients and to define a predictive model of remission based on several factors. Between 1973 to 1989, 46 patients (25 male, 21 female), aged 38 +/- 18 years, entered the study. Clinically EAT was paroxysmal in 23 patients, permanent in 12 and repetitive in 11; six patients were asymptomatic. Thirty-five complained of palpitations; dyspnoea, dizziness and syncope were also reported less frequently. All patients underwent an electrophysiological study to clarify the mechanism of the arrhythmia and to localize its site of origin. In 15 patients no heart disease was documented. Five patients underwent surgery and were excluded from subsequent analysis. Seven patients were discharged without antiarrhythmic treatment. We defined remission as the absence of recurrence of EAT within 6 months from withdrawal of therapy. Logistic regression was applied to identify potential predictors of remission. Seven clinical and electrophysiological covariates were entered in the model; univariate and multivariate tests were performed, using the GLIM3 statistical package. During a follow-up period of 5.1 +/- 4.5 years, 14 instances of remission (34%) were observed in 5/22 patients with paroxysmal EAT, 4/8 patients with permanent EAT and 5/11 patients with repetitive EAT. Mean age of patients with remission was 25 +/- 14 years vs 45 +/- 15 years in the group without remission. No covariate had an independent predictive value.(ABSTRACT TRUNCATED AT 250 WORDS)

Left atrial isolation associated with mitral valve operations.

Surgical isolation of the left atrium was performed for the treatment of chronic atrial fibrillation secondary to valvular disease in 100 patients who underwent mitral valve operations. From May 1989 to September 1991, 62 patients underwent mitral valve operations (group I); 19, mitral valve operations and DeVega tricuspid annuloplasty (group II); 15, mitral and aortic operations (group III); and 4, mitral and aortic operations and DeVega tricuspid annuloplasty (group IV). Left atrial isolation was performed, prolonging the usual left paraseptal atriotomy toward the left fibrous trigone anteriorly and the posteromedial commissure posteriorly. The incision was conducted a few millimeters apart from the mitral valve annulus, and cryolesions were placed at the edges to ensure complete electrophysiological isolation of the left atrium. Operative mortality accounted for 3 patients (3%). In 79 patients (81.4%) sinus rhythm recovered and persisted until discharge from the hospital. No differences were found between the groups (group I, 80.7%; group II, 68.5%; group III, 86.7%; group IV, 75%; p = not significant). Three late deaths (3.1%) were registered. Long-term results show persistence of sinus rhythm in 71% of group I, 61.2% of group II, 85.8% of group III, and 100% of group IV. The unique risk factor for late recurrence of atrial fibrillation was found to be preoperative atrial fibrillation longer than 6 months. Due to the satisfactory success rate in recovering sinus rhythm, we suggest performing left atrial isolation in patients with chronic atrial fibrillation undergoing valvular operations.

[Left atrial electric isolation in the treatment of atrial fibrillation secondary to rheumatic valvular disease]. / L'isolamento elettrico dell'atrio sinistro per il trattamento della fibrillazione atriale secondaria a valvulopatia reumatica.

BACKGROUND: Surgical isolation of the left atrium was performed for the treatment of chronic atrial fibrillation secondary to valvular disease in 100 patients who underwent valve surgery. METHODS: From May 1989 to September 1991, 62 patients underwent mitral valve surgery (Group I), 19 underwent mitral valve surgery and DeVega tricuspid annuloplasty (Group II), 15 underwent mitral and aortic surgery (Group III), and 4 patients underwent mitral and aortic surgery and DeVega tricuspid annuloplasty (Group IV). Left atrial isolation was performed prolonging the usual left paraseptal atriotomy towards the left fibrous trigone anteriorly, and the postero-medial commissure posteriorly. The incision was conducted a few millimeters apart from the mitral valve annulus, and cryolesion were placed at the edges to ensure complete electrophysiological isolation of the left atrium. RESULTS: Operative mortality accounted for 3 cases (3%). In 79 patients (81.4%) sinus rhythm recovered and persisted until discharge from the hospital. No differences were found between the groups (Group I: 80.7%; Group II: 68.5%; Group III 86.7%, Group IV 75% - p = N.S.). Three cases of late mortality (3.1%) were registered. long-term results showed persistence of SR in 71% of Group I, 61.2% of Group II, 85.8% of Group III, and 100% of Group IV. The unique risk factor for late recurrency of atrial fibrillation was found to be a duration of preoperative AF longer than 6 months. CONCLUSIONS: Due to the high success rate in recovering the sinus rhythm, we suggest left atrial isolation in patients with chronic atrial fibrillation undergoing valvular surgery.

Selective growth inhibition of a human malignant melanoma cell line by sesame oil in vitro.

Ayurveda, an ancient and comprehensive system of natural medicine, recommends regular topical application to the skin of sesame oil, above all other oils, as a health-promoting procedure. We examined the effect of sesame oil and several other vegetable oils and their major component fatty acids on the proliferation rate of human normal and malignant melanocytes growing at similar rates in serum-free media. We found that sesame and safflower oils, both of which contain large amounts of linoleate in triglyceride form, selectively inhibited malignant melanoma growth over normal melanocytes whereas coconut, olive and mineral oils, which contain little or no linoleate as triglyceride, did not. These oils were tested at a range of 10-300 micrograms/ml. We found that of the fatty acids tested, only linoleic acid was selectively inhibitory while palmitic and oleic were not. These fatty acids were tested in the range of 3-100 micrograms/ml. These results suggest that certain vegetable oils rich in linoleic acid, such as the sesame oil, recommended for topical use by Ayurveda, may contain selective antineoplastic properties which are similar to those demonstrated for essential polyunsaturated fatty acids and their metabolites. This suggests that whole vegetable oils may have potential clinical usefulness.

[The nonpharmacological treatment of tachyarrhythmias. The surgery of supraventricular arrhythmias not due to pre-excitation]. / Il trattamento non farmacologico delle tachiaritmie. La chirurgia delle aritmie sopraventricolari non da preeccitazione.

Surgery can provide treatment for supraventricular tachyarrhythmias without operative risk and with a definite improvement of patients' quality of life. Ectopic atrial tachycardia is a rare but invalidating arrhythmia that may lead to cardiomyopathy: intraoperative mapping is necessary for the location of the location of the ectopic focus; in our experience, surgical, cryothermal or isolation ablation of the area were effective in 9 patients out of 9, with regression of the cardiomyopathy. Atrioventricular node reentry tachycardia is a reentry tachycardia which is often associated with Wolff-Parkinson-White syndrome and is amenable to surgical treatment. Discrete cryolesions around the Koch triangle are effective in interrupting the atrial inputs to the atrioventricular node and therefore the reentry mechanism: in our experience, 7 patients were successfully treated without operative mortality: 3 patients underwent surgical ablation of Kent bundles as well. Atrial fibrillation is not based on a well-defined mechanism, and therefore does not permit an electrically-guided surgical treatment. However, in case of atrial septal defect it is possible to isolate the enlarged right atrium in order to allow sinus rhythm to activate the left atrium and ventricles.(ABSTRACT TRUNCATED AT 250 WORDS)

[Surgical treatment of supraventricular tachycardia]. / Khirurgicheskoe lechenie nadzheludochkovykh takhikardii.

The article deals with the modern approaches to the treatment of supraventricular tachycardia . The authors analyse the results of operations in ectopic atrial tachycardias, the Wolff-Parkinson-White syndrome, modal re-entry tachycardias, and atrial fibrillation . The last-named is of most interest because the authors possess experience in a new operation for isolation of the internodal tracts. In all conditions the authors obtained convincing evidence on the efficacy of modern surgical treatment in supraventricular tachycardias.

[Indications and results of transcatheter ablation and surgery in paroxysmal reentry nodal tachycardia]. / Indicazioni e risultati dell'ablazione transcatetere e della chirurgia nelle tachicardie parossistiche da rientro "nodale".

In patients with nodal tachycardia refractory to medical therapy, transcatheter or surgical ablation is necessary. From January 1989 to December 1990, in 26/42 patients with nodal tachycardia, referred to our institution for electrophysiologic evaluation, transcatheter ablation by radiofrequency (20 patients) or surgical ablation by perinodal cryo (6 patients) was performed. In all these cases, a total refractoriness to several antiarrhythmic drugs alone or in association had been observed. The radiofrequency current, generated by the Osypka HAT 100 device, was administered through a tripolar USCI 7 F catheter. The ideal site for energy delivery was defined on the basis of a mapping, performed in the A-V junction area. In order to find out the most premature retrograde atrial activation, the following areas were explored: right bundle, atrial His bundle, peri-nodal region, proximal His bundle and coronary sinus ostium. Local atrial activation time was evaluated during nodal tachycardia by delivering a premature ventricular extrastimulus to discover the atrial deflection from the ventricular one. In the selected area, 5 applications (range 1-12) of 20-25 W power radiofrequency energy for 5-30 s were delivered on average. A complete prevention of nodal tachycardia was achieved in 18/20 patients (90%). Only in 2 patients a total A-V block was induced. The pre- and post-procedure values are as follows: AH: pre 71 +/- 19, post 113.6 +/- 50; HV: pre 45.5 +/- 8, post 47 +/- 6; aWP: pre 353 +/- 57, post 391 +/- 87; rWP: pre 322 +/- 58, post 411 +/- 58. In 10/18 cases the AH interval was normal after radiofrequency application.(ABSTRACT TRUNCATED AT 250 WORDS)

The use of sesame oil and other vegetable oils in the inhibition of human colon cancer growth in vitro.

Sesame contains large quantities of the essential polyunsaturated fatty acid (PUFA), linoleic acid, in the form triglycerides. The antineoplastic properties of many PUFAs such as linoleic acid and their metabolites are known. We tested the hypothesis that natural vegetable oils, such as sesame oil and its component linoleic acid, when added to human colon adenocarcinoma cells growing in tissue culture would inhibit their growth and that normal colon cells would not be similarly affected. Three human colon cancer cell lines and one normal human colon cell line were exposed to the following: (1) pure linoleic acid; (2) lipase-digested sesame oil; (3) undigested sesame oil; (4) five additional common vegetable oils; (5) mineral oil. Linoleic acid inhibited the in vitro growth of all three malignant human colon adenocarcinoma cell lines. The normal colon cell line showed dramatically less inhibition of growth. Lipase-digested sesame oil (LDSO) and undigested sesame oil (UDSO) produced greater inhibition of growth of all three malignant colon cell lines than of the normal colon cells. Five other common vegetable oils containing various amounts of PUFAs such as corn, soybean, safflower, olive and coconut oils, all in their lipase-digested form, were found to dramatically inhibit the growth of the HT-29 malignant human colon cell line. Undigested olive and safflower oils also inhibited the HT-29 cells although not as markedly as the lipase-digested oils. Mineral oil did not inhibit the growth of HT-29 cells. Both lauric and palmitic acid, which are saturated fatty acids found in abundance in coconut oil inhibits the HT-29 cells more strongly than linoleic acid, while oleic acid did not inhibit. We conclude that many vegetable oils including sesame contain in vitro antineoplastic properties and that this finding warrants further investigation both in vitro and in vivo to assess their possible chemotherapeutic potential.

Electrocardiographic changes suggestive of myocardial ischemia elicited by dipyridamole infusion in acute rejection early after heart transplantation.

Acute cardiac rejection, syndrome X, and arterial hypertension can induce small vessel damage and, therefore, restriction of coronary reserve in the presence of normal epicardial coronary arteries. A characteristic response pattern to dipyridamole (DIP) infusion has been previously described in syndrome X and arterial hypertension: ST segment depression without any measurable systolic dysfunction. The aim of this study was to establish whether acute cardiac rejection might induce electrocardiographic alterations during DIP infusion. Changes in the 12-lead electrocardiogram and two-dimensional echocardiogram during high-dose DIP infusion (up to 0.84 mg/kg in 10 minutes) were evaluated within 24 hours of endomyocardial biopsy in 14 transplanted patients. A total of 47 biopsy-controlled DIP studies were performed within 5 weeks after cardiac transplantation. For each patient, at least 7 days elapsed between two consecutive studies. Electrocardiographic and echocardiographic tracings were analyzed without prior knowledge of endomyocardial biopsy findings. No remarkable side effects occurred in any case, so that the DIP study could be completed in all patients. A diagnostic (greater than 0.1 mV) ST segment depression was found in 11 studies. The sensitivity and specificity of DIP-induced ST segment depression for the detection of biopsy-proven acute rejection were 72% and 94%, respectively. These data show that DIP stress is feasible and safe in transplanted patients and that acute cardiac rejection can be accompanied by DIP-induced ST segment depression without detectable impairment in systolic function. These changes might provide noninvasive markers for surveillance of rejection.

Arrhythmogenic right and left ventricular disease: evaluation by computed tomography and nuclear magnetic resonance imaging.

Ventricular tachycardia may represent the first sign of an unknown cardiomyopathy; fewer data are available on the anatomical substrate of the arrhythmia. The aim of the study was to characterize better those patients who usually do not have haemodynamic impairment, but in whom the arrhythmia may be severely invalidating. To that purpose, two recent and sophisticated radiological methods were used, computed tomography (CT) and nuclear magnetic resonance (NMR); both methods allowed a precise characterization of the morphology and function of the right and left ventricle; a tissue analysis was performed that identified regions of lipomatous degeneration both in the right and the left ventricle, particularly with NMR. In conclusion, CT and particularly NMR appear to be able to reveal minimal changes suggestive of a right and/or left cardiomyopathy whose first manifestation is ventricular tachycardias.

Correlation between preferred sugar ring conformation and activity of nucleoside analogues against human immunodeficiency virus.

Analysis of the solid-state conformations of six active and two inactive anti-human immunodeficiency virus nucleoside analogues is used to correlate conformational features with the relative activities of the compounds. Ten of the 11 observations of the active compounds (3'-azido-3'-deoxythymidine, 3'-azido-2',3'-dideoxyuridine, 3'-azido-2',3'-dideoxy-5-ethyluridine, 2',3'-dideoxyadenosine, 2',3'-dideoxycytidine, and 3'-deoxythymidine) have C3'-exo sugar ring conformations. The only exception is one of the two molecules of 3'-deoxythymidine. Four have unusual low anti glycosyl link conformations coupled with unusual C3'-exo/C4'-endo sugar ring conformations. The inactive compounds, 2',3'-dideoxyuridine and 3'-(propyl-2-ene)-2',3'-dideoxyuridine, have C3'-endo conformations. The C3'-exo and C3'-endo conformations place C5' in axial and equatorial positions, respectively. This affects the location of the 5'-hydroxyl group in relation to the location of the base. The 5'-hydroxyl group is the site of phosphorylation of the nucleoside and the observation of this conformational preference of the active compounds may be of importance for the development of new nucleosides with activity against human immunodeficiency virus.