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Probiogenomic analysis of functional potential and safety of L. plantarum 8p-a3 and DMC-S1 strains: in silico vs in vitro and in vivo data.

The molecular basis of the beneficial effects and the causes of the negative effects of probiotics are not entirely clear. Clarifying these issues is important for understanding the biology and assessing the safety of the microbes. Omics technologies have opened up new resources for obtaining relevant knowledge. Here, for the first time, we present the results of a comparative analysis of the functional potential and safety of two L. plantarum strains: the approved probiotic 8p-a3 and the Drosophila intestinal resident, which exhibit opposite effects on D. melanogaster as the model host organism. Through genomic analysis, extracellular vesicle studies, and in vitro and in vivo assays, we have identified the common and specific characteristics of the strains. The strains proved to be similar in a set of genes that determine benefits to the host organism, as well as in the presence of some risk factors. Significant differences between the strains are related to genes responsible for adhesion, sialic acid metabolism, mucin degradation, antimicrobial peptides, tannin resistance, and immunomodulation. In silico data correlated with in vitro and in vivo data, with the exception of antimicrobial sensitivity. Pronounced differences between the strains were found in terms of the composition and biological effects of their vesicles. In vivo data on the effects of the strains correlate with the corresponding data of their vesicles in the fruit fly model. The results obtained open up new facets in L. plantarum strains relevant for evaluating the functionality and safety of probiotics.IMPORTANCEUsing a probiogenomic approach, common and specific features regarding functionality and safety were identified in the strains (the approved probiotic strain L. plantarum 8p-a3 and the Drosophila intestinal bacterium L. plantarum DMC-S1), which exhibit opposite effects on the model host organism (D. melanogaster). The genomic analysis was supplemented by the analysis of extracellular vesicles of the strains. Comparative analysis of in silico data in combination with in vitro and in vivo studies was performed, and unexpected capabilities of the strains were discovered. Novel factors, essential for evaluating the safety of probiotics, were identified. New facets in the interplay of probiotic bacterium with host organism have been revealed.

Animals

Small cell undifferentiated bronchogenic carcinoma: current status with emphasis upon the role of chemotherapy.

Current opinions concerning tumor biology and clinical characteristics of small cell undifferentiated bronchogenic carcinoma are reviewed. Special emphasis is placed upon chemotherapy for this lung cancer subtype and presently achievable response rates and survival times are presented. A series of 16 patients with small cell undifferentiated bronchogenic carcinoma is also presented. All patients were given cyclophosphamide, methotrexate, vincristine, and procarbazine as treatment for this neoplasm. Sixty-eight percent of patients responded and the survival time in partial responders was 33.4+ weeks as compared to 13.7 weeks with nonresponders. These data correlate well with the previous data of Alberto et al [Alberto P, Brunner KW, Martz G, Obrect JP: Cancer 38:2208--2216, 1976], who investigated the same agents for this tumor, but at higher dosages.

Adult

A model for steroid transport across biological membranes.

The absorption of a range of steroids (water soluble to lipid soluble) in the mouth was investigated under standard conditions and using gas chromatography. A two-compartment open model was used to describe the absorption of these steroids into, and through, the membrane. Rate constants were calculated on this basis using a feathering technique, and were used in an analogue computer program to predict steroid concentration which agree favourably with experimental data. Correlations between absorption and partition data were made in an attempt to relate the proposed model to anatomical features of the absorptive membrane and to make comparison with models proposed to describe drug absorption across the intestinal mucosa.

Absorption

Effect of improved assay sensitivity on luteinizing hormone pulse detection after gonadotropin-releasing hormone antagonist treatment in man.

When serum levels of a hormone are at or below the detection limit of the measurement system, accurate characterization and quantitation of pulsatile hormone secretion may be difficult. This point is well illustrated in this study, which used two immunoassays with markedly different assay sensitivities to quantitate pulsatile LH secretion in men in whom serum LH levels had been suppressed by the administration of a GnRH antagonist. Five normal men received 5 mg Nal-Glu, sc, daily for 21 days. Blood was drawn at 10-min intervals over 8 h on days 0 and 21. Samples were assayed in triplicate in both a conventional LH RIA with a sensitivity of 0.6-1.0 IU/L and a two-site-directed ultrasensitive immunofluorometric assay (IFMA) with assay sensitivity ranging from 0.05-0.125 IU/L. LH pulses were analyzed by Cluster analysis (C) and were corroborated by the Detect algorithm (D). Nal-Glu suppressed LH (C) pulse amplitude from 4.0 +/- 0.7 to 0.40 +/- 0.03 IU/L by LH RIA and from 7.8 +/- 2.1 to 0.21 +/- 0.04 IU/L by LH IFMA. An apparent reduction in LH pulse number was observed in the RIA data on day 21 by both pulse detection methods [4.2 +/- 0.4 vs 2.4 +/- 0.2/8 h on days 0 and 21 by C (P < 0.005); 5.8 +/- 0.8 vs. 2.8 +/- 0.7 by D (P < 0.05)]. However, the IFMA measurements in the same samples using the more sensitive LH IFMA showed no difference in pulse number between days 0 and 21. The RIA data correlated well with the IFMA data, with a concordance coefficient ranging from 0.66-0.9. In summary, the Nal-Glu GnRH antagonist markedly decreases LH pulse amplitude, but not pulse frequency. These observations are consistent with competitive inhibition of GnRH action at the pituitary site by the Nal-Glu antagonist; they indicate that assay characteristics can significantly affect quantitation of hormone pulse pattern and underscore the need for ultrasensitive LH assays for accurate assessment of LH pulse characteristics when LH levels are low or suppressed.

Adult

The distribution of isoprenoid quinones in streptococci of serological groups D and N.

The isoprenoid quinone contents of streptococci of serological groups D and N were investigated. Streptococcus faecalis, S. faecalis subsp. liquefaciens and S. faecalis subsp. zymogenes strains contained demethylmenaquinones with nine isoprene units as their major isoprenologues. Menaquinones with eight isoprene units predominated in S. faecium subsp. casseliflavus and S. faecium subsp. mobilis whereas menaquinones with nine isoprene units constituted the major components in strains of S. cremoris, S. cremoris subsp. alactosus, S. lactis and S. lactis subsp. diacetylactis. Strains of S. avium, S. bovis, S. durans, S. equinus, S. faecium, S. raffinolactis and S. suis contained neither menaquinones nor ubiquinones. The isoprenoid quinone data correlate well with other kinds of data on these organisms and are of value in the classification of these bacteria.

Enterococcus faecalis

Vectorcardiographic-hemodynamic correlations in adult aortic stenosis.

Thirty-nine vectorcardiographic (VCG) data from 45 patients with pure adult aortic stenosis have been tested as to their ability to reflect quantitatively the peak systolic left ventricular pressure (LVPSP), the left ventricular end diastolic pressure (LVEDP), and the X-ray estimated heart volume. VCG was recorded with the axial lead system and simple and multiple linear regression analyses were applied. Eight VCG data correlated significantly (p less than 0.001) with LVPSP, the best indicator being the maximum posterior dislocation in the Z lead (r = 0.65). Through multiple regression analysis a formula was derived which gave a correlation coefficient between observed and calculated pressures of 0.82. The best indicator of LVEDP was the maximum positive P amplitude in the X lead (r = 0.41). The relationship was, however, too poor to have practical significance. A good correlation was found between ST segment dislocation and heart volume (r = 0.65), in good accordance with previous observations as to the effect of right ventricular dilatation on the ECG. The study illustrates how ventricular volume and pressure exert different effects on the ECG, and how all the important hemodynamic aspects in aortic stenosis to some degree are reflected. Only the pressure correlations have, however, practical importance.

Aortic Valve Stenosis

Multivariate methods for binary longitudinal data with heterogeneous correlation over time.

Clustered binary data occur frequently in biostatistical work. One particular application is in binary longitudinal data, where several visits are available for the same individual. Several approaches have been proposed for the analysis of clustered binary data. In Rosner, a polychotomous logistic regression model was proposed which is a generalization of the beta-binomial distribution and allows for person- and visit-specific covariates, while controlling for clustering effects. One assumption of this model is that all pairs of visits within an individual are equally correlated, which may be inappropriate if several visits are available over a long follow-up period. In this paper, this approach is extended to allow for heterogeneous correlation over time. The total time period is divided into subintervals and a beta-binomial mixture model is introduced to estimate odds ratios relating outcomes for pairs of visits both within a subinterval as well as in different subintervals. To include covariates, an extension of the polychotomous logistic regression model is proposed, which allows one to estimate effects of person-, subinterval-, and visit-specific covariates, while controlling for clustering using the beta-binomial mixture model. This model is applied to the analysis of respiratory symptom data in children collected over a 14-year period in East Boston, MA, in relation to maternal and child smoking, where the unit is the child and symptom history is divided into early-adolescent and late-adolescent symptom experience.

Humans

An analysis of least restrictive environment placement variables in physical education.

The purpose of this study was to determine the variables related to the successful least restrictive placement of students with disabilities into physical education classes. Subjects were 470 school building representatives and 62 adapted physical education professors throughout the nation. Confidence interval estimates (95%) of school building data correlated highest on relative importance with university census data on 8 of 37 total variables: motor ability test scores, developmental scale scores, reaching individualized education program instructional objectives, special education teacher recommendation, regular physical educator recommendation, activity offerings, classroom physical accessibility, and safety considerations. These represent those variables that should be used in some "best practices" combination by school personnel in making decisions regarding relevant students' class placement within physical education least restrictive environment alternatives. In addition, staff recommendation category variables were considered more important than test score, student related, class related, and administrative category variables.

Persons with Disabilities

Correlation of in vivo collagen degradation rate with in vitro measurements.

The rate of in vitro enzymatic degradation of various materials based on collagen has been determined by a novel mechanochemical method, and has been compared with the extent of degradation resulting from subcutaneous implantation in guinea pigs. In vitro data correlate well with in vivo data. It is suggested that the simple in vitro method described is an effective means of screening a large number of materials based on collagen for their ability to resist degradation during implantation in animals.

Animals

Path analysis of palmar ridge counts.

The methods for path analysis of family resemblance (Rao et al., '74) are employed to test hypotheses concerning the inheritance of a-b, b-c and c-d palmar ridge counts using the correlation data of Pateria ('74). Homogeneity chi-square tests of the various familial correlations provide no evidence for sex-linkage of either kind, and also suggest that maternal effects are absent. The path coefficient model employed here involves heritability (additive) and common sibling environment. Variance components show that both heritability and common environment are significant, and account for most of the variation at each of the three ridge count area; b-c has the highest heritability, significantly higher than that for a-b or c-d.

Dermatoglyphics

Occupationally induced neoplasms of the lung and pleura.

The relationship between asbestos and mesothelioma has been well delineated in the past. The epidemiologic, clinical, radiologic, and pathologic features of mesothelioma are discussed with reference to the diagnostic evaluation of asbestos-exposed patients. The extensive epidemiologic data correlating asbestos, tobacco smoke, and induction of lung carcinoma are also reviewed. These data provide a model for evaluation of other occupationally induced lung carcinogens such as organic and metallic industrial inhalants.

Humans

Experimental models for spinal cord injury research: physical and physiological considerations.

This paper describes historical and current experimental models used to develop our current understanding of the biomechanics and pathophysiology of traumatic spinal cord injury; the advantages and limitations of current experimental models; considerations for selecting an appropriate injury model based on experimental objectives; and key physiological factors in the spinal cord injury response that may interact with the injury response and alter the outcome. All of the above must be considered in the development and selection of an appropriate experimental injury model that meets specific needs. Various experimental models have been developed to study spinal cord injury and the pathophysiological and physical mechanisms responsible for tissue damage and loss of function. Such modeling may involve inherently different biomechanical variables with alternative outcomes and purposes. There is not, therefore, a single "ideal" experimental injury model just as there is no "stereotypical" clinical spinal cord injury. Instead, the goals and objectives of the research dictate specific requirements on the model. In all cases, however, both physical and physiological aspects of the model should be considered, and measured if possible, to ensure interlaboratory comparability and possible clinical relevance. Also, experimental techniques, especially anesthesia, and surgical procedures, should be carefully reviewed for interactions with the injury response or potential therapeutic interventions to ensure validity of interpretation. It is hoped that data correlating physical spinal cord injury parameters with functional outcome will ultimately be combined with data on vertebral injury and spinal failure mechanics to further our understanding of clinical injury. Such approaches should lead to interventions that reduce the incidence and severity of traumatic human spinal cord injury.

Animals

Further examination of seventeen mutations in Escherichia coli F1-ATPase beta-subunit.

Seventeen mutations in beta-subunit of Escherichia coli F1-ATPase which had previously been characterized in strain AN1272 (Mu-induced mutant) were expressed in strain JP17 (beta-subunit gene deletion). Six showed unchanged behavior, namely: C137Y; G142D; G146S; G207D; Y297F; and Y354F. Five failed to assemble F1F0 correctly, namely: G149I; G154I; G149I,G154I; G223D; and P403S,G415D. Six assembled F1F0 correctly, but with membrane ATPase lower than in AN1272, namely: K155Q; K155E; E181Q; E192Q; D242N; and D242V. AN1272 was shown to unexpectedly produce a small amount of wild-type beta-subunit; F1-ATPase activities reported previously in AN1272 were referable to hybrid enzymes containing both mutant and wild-type beta-subunits. Purified F1 was obtained from K155Q; K155E; E181Q; E192Q; and D242N mutants in JP17. Vmax ATPase values were lower, and unisite catalysis rate and equilibrium constants were perturbed to greater extent, than in AN1272. However, general patterns of perturbation revealed by difference energy diagrams were similar to those seen previously, and the new data correlated well in linear free energy relationships for reaction steps of unisite catalysis. Correlation between multisite and unisite ATPase activity was seen in the new enzymes. Overall, the data give strong support to previously proposed mechanisms of unisite catalysis, steady-state catalysis, and energy coupling in F1-ATPases (Al-Shawi, M. K., Parsonage, D. and Senior, A. E. (1990) J. Biol. Chem. 265, 4402-4410). The K155Q, K155E, D242N, and E181Q mutations caused 5000-fold, 4000-fold, 1800-fold, and 700-fold decrease, respectively, in Vmax ATPase, implying possibly direct roles for these residues in catalysis. Experiments with the D242N mutant suggested a role for residue beta D242 in catalytic site Mg2+ binding.

Catalysis

The effect of premenstrual anxiety and depression on cognitive function.

The Depression Adjective Check List, State-Trait Anxiety Inventory, and a battery of factor analytically derived cognitive tests sensitive to anxiety or depression were administered to 50 women between the ages of 30 and 45 during the 4 days prior to the onset of menstruation and again 2 weeks later. Testing sessions were scheduled on the basis of a previously completed Menstrual Distress Questionnaire. There were significant increases in anxiety and depression during the premenstruum. However, no statistically significant differences were found in cognitive test performance, and correlation data failed to support any consistent relationship between premenstrual mood and cognitive function. Moreover, no significant correlations were found between premenstrual complaints on the Menstrual Distress Questionnaire and either cognitive test performance or mood scores obtained during the premenstrual testing sessions. It was concluded that the magnitude of the premenstrual mood change was not great enough to affect intellectual function. Alternative explanations of the absence of decrements in performance are discussed.

Adult

Two minute slope inhalation technique for cerebral blood flow measurement in man. 1. Method.

The two minute slope method of measuring cerebral blood flow (CBF) by inhalation of 133Xe is described. It requires the subject to remain still for only two minutes and is thus applicable to a wide variety of patients and to investigations involving brief physiological stimuli. The influence of extracerebral blood flow on CBF calculated by this method has been studied. Results from the two minute slope inhalation method using two minutes of data correlate well with those obtained by carotid injection using either two minutes or 10 minutes of data.

Administration, Intranasal

[Clinico-electrophysiologic studies of experimental herpetic encephalitis].

Studies on animals demonstrated that in experimental herpetic encephalitis there is a diffuse retardation of background bioelectric brain activity and a proxysmal activity of 2 types: peek complex-slow waves 3 per 1 sec. and periodical paroxysmal complexes. There is also an increase of latent periods, duration and amplitudes of visual evoked potentials. Electrophysiological data correlate with the clinical picture of herpetic encephalitis and pathomorphological changes in the CNS. The obtained data are discussed with consideration bor the theory of neuron epileptization and hemodynamical disturbances.

Animals

Morbidity experience of air traffic control personnel--1967--77.

The morbidity experience of 28,086 air traffic controllers has been examined from 1967--77 with particular emphasis to the potential effects of job demands on ATC health. The morbidity experience of air traffic controllers does not appear excessive, except for psychoneurotic disorders, compared with the experience of other outside groups studied. Additionally, a lack of association between disease occurrence and occupation is observed in the data correlating disease occurrence with length of service and age. While some isolated trends found in these data are supportive of an occupation/disease relationship, they are neither--as would be expected if the association were a strong one--impressive nor consistent. Although anticipated empirically, one of the more interesting results of the study was quantification of the substantial differences found to exist in the incidence of disease before and after the second-career legislation.

Adult

Clinical application of electrical impedance for the study of arterial insufficiency.

A four-electrode impedance plethysmography containing a dedicated computer has been developed for evaluating arterial insufficiency in the clinical noninvasive vascular laboratory. Measurements obtained by the impedance plethysmograph were compared with measurements obtained by the Doppler ultrasound technique. Five case reports demonstrate that electrical impedance measurements can feasibly be obtained in the clinical setting and that the information is useful in treating patients with arterial insufficiency. Results indicate that electrical impedance data correlate better with the clinical symptoms reported by the patient than do the Doppler systolic pressure data. The impedance plethysmography measurements are particularly useful when considered in conjunction with the Doppler measurements.

Adult