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[Transmission and expression of malignancy in somatic hybrid cell lines (hamster/hamster, mouse/mouse, hamster/mouse)].

Various characteristics of transformation were studied in subclones isolated from a hybrid cell line obtained by fusion of two Chinese hamster sub-lines having the same origin but presenting different properties, particularly in respect to heterotransplantability. Different subclones were obtained by cloning on semisoft agar. Transplantability, plating efficiency, agglutinability by concanavalin A and actinomycin D resistance were studied in parallel with the evolution of the karyotype to try to find a correlation between these various parameters. A relationship seems to exist between a chromosome marker arising in the hybrid and the percentage of tumours. The second part of this work dealth with the study of intra and interspecies hybrids, one of the parents of which was a normal, fibroblastic cell and the other of which contained the polyoma virus genome. In the hybrid cell this viral genome was expressed at several levels. Firstly, in the formation of specific polyoma virus-induced antigens and secondaryly, in surface properties normally considered related to the expression of tumorigenicity. Nevertheless, tumour development was repressed. Though the presence of characteristic antigens seemed necessary for the expression of malignant transformation, presence alone was not sufficient to induce malignant transformation of the cell. The study of inter-species mouse/hamster hybrids showed that this situation is not general. For this we examined the properties of hybrid cells between, on the one hand, a mouse tumorigenic cell bearing polyoma virus genetic information and, on the other, non-tumorigenic mouse or hamster cell. In this case the complete hamster genome could bot repress malignancy whereas a few mouse chromosomes sufficed to code for the expression of virus-induced tumour antigens and various malignant properties. It may be hoped that these hybrids could be used to pin-point the chromosome localization of the genetic factors of malignancy and could be used in immunoprotection studies or immunotherapy research.

Agglutination

[The nursing dimension in palliative care].

In this 250-bed general hospital, nursing care for the dying focuses not on recovery but on self-actualization. In a broader context, patients also benefit from nursing's theory-based approach. A parallel between the evolution of the patient and the nursing process is established.

Adult

Teaching medical professionals to retrieve and manage medical information.

Popularity of the personal computer has prompted physician interest in direct access to the medical literature from sophisticated electronic data retrieval systems. This paper describes the educational programs developed by the library at the George Washington University Medical Center in response to this interest and growing national trend. As a result of these programs, the role of the librarian has changed permanently. Librarians are now perceived by faculty as educational specialists and information consultants. The evolution in libraries parallels the technological changes taking place in other biomedical communications units. The authors recommend the positive outcomes from adapting traditional roles to meet user's needs in a changing environment.

Humans

[The evolutionary principle in histology].

The A.A. Zavarzin's law of parallel lines in tissue evolution showing the appearance of a common tissue organization pattern is the major regularity of the cellular development of animals in phylogenesis. It carries out the metabolism principally similar in all animals in their interaction with the environment. The A.A. Zavarzin's law of parallel lines is also the main regularity of the evolution of tissue interrelations bringing about the principal processes of metabolism. The tissue evolution as well as the evolution of the organism is under the influence of factors of heredity, variability and natural selection. These factors however have an influence mediated by the organism evolution. The precess of cephalization represents a fairly important manifestation of the evolution of animals. The theory of general histogenesis reflects the main regularity of the cellular development in ontogenesis of man and animals. Being a further development of the conception of the A.A. Zavarzin's tissue evolution this theory shows the development of the animal cellular structure as a single general process of histogenesis, beginning with a zigote and continuing till the end of the organism life. The integration, heterochronia and determination manifest themselves in this process of differentiation of cells, tissues and intertissue relations.

Biological Evolution

[Several methodologic problems of evolutionary histology in light of the findings of molecular genetics].

The paper elucidates certain methodological problems of evolutionary histology. The principal attention is given to the necessary synthesis of modern molecular biology and genetics and evolutionary histology. Modern data on the levels of the organization of the living matter and their significance for the rightness of the A.A. Zavarzin's theory of parallel lines in the tissue evolution are presented. The hypothesis of an application of the theory of parallel lines in the hereditary variability by N.I. Vavilov to the analysis of regularities of the tissue evolution is set forth. The hypothesis is proposed that mutation changes of similar genes in representatives of different types of animals underlie the regularities of the tissue evolution discovered by A.A. Zavarzin, and epigenomic changes of regulation systems occurring most frequently in the process of ontogenesis of organisms lie in the basis of the divergent evolution of tissues after N.G. Chlopin.

Biological Evolution

Massively parallel approaches for characterizing noncoding functional variation in human evolution.

The genetic differences underlying unique phenotypes in humans compared to our closest primate relatives have long remained a mystery. Similarly, the genetic basis of adaptations between human groups during our expansion across the globe is poorly characterized. Uncovering the downstream phenotypic consequences of these genetic variants has been difficult, as a substantial portion lies in noncoding regions, such as cis-regulatory elements (CREs). Here, we review recent high-throughput approaches to measure the functions of CREs and the impact of variation within them. CRISPR screens can directly perturb CREs in the genome to understand downstream impacts on gene expression and phenotypes, while massively parallel reporter assays can decipher the regulatory impact of sequence variants. Machine learning has begun to be able to predict regulatory function from sequence alone, further scaling our ability to characterize genome function. Applying these tools across diverse phenotypes, model systems, and ancestries is beginning to revolutionize our understanding of noncoding variation underlying human evolution.

Humans

Digestive histochemical reactions in rats after space flight of different duration.

Different histochemical reactions were searched in the digestive tract of rats that flighted on Soviet biosatellites, 5, 7, 13, 14 and 18 1/2 days (2). Space flight decreased glycoprotein (GP) content of sublingual glands and of gastric and intestinal mucosa, and increased reactions for leucin-aminopeptidase (LAP) and acid phosphatase (ACP) of the small intestine. These responses were in relation with the duration of the flight. For searching some possible mechanism by which they occurred, same investigations were done in rats submitted at soil level to a contention hypokinesia (HK), for mimicking space flight. After HK, similar histochemical responses were founded as after the true flight. The evolution of histochemical responses paralleled the corticosterone hypersecretion, suggesting a causal correlation, but they were also the same in adrenalectomised rats. Effectory hormonal pathways are thus further to be searched, as well as a correlation with the intermediary metabolism, as a similar evolution was founded in pancreatic, insulin secreting, B cells.

Animals

Chondrocytes in agarose culture synthesize a mechanically functional extracellular matrix.

The ability of chondrocytes from calf articular cartilage to synthesize and assemble a mechanically functional cartilage-like extracellular matrix was quantified in high cell density (approximately 10(7) cells/ml) agarose gel culture. The time evolution of chondrocyte proliferation, proteoglycan synthesis and loss to the media, and total deposition of glycosaminoglycan (GAG)-containing matrix within agarose gels was characterized during 10 weeks in culture. To assess whether the matrix deposited within the agarose gel was mechanically and electromechanically functional, we measured in parallel cultures the time evolution of dynamic mechanical stiffness and oscillatory streaming potential in uniaxial confined compression, and determined the intrinsic equilibrium modulus, hydraulic permeability, and electrokinetic coupling coefficient of the developing cultures. Biosynthetic rates were initially high, but by 1 month had fallen to a level similar to that found in the parent calf articular cartilage from which the cells were extracted. The majority of the newly synthesized proteoglycans remained in the gel. Histological sections showed matrix rich in proteoglycans and collagen fibrils developing around individual cells. The equilibrium modulus, dynamic stiffness, and oscillatory streaming potential rose to many times (>5x) their initial values at the start of the culture; the hydraulic permeability decreased to a fraction (approximately 1/10) that of the cell-laden porous agarose at the beginning of the culture. By day 35 of culture, DNA concentration (cell density), GAG concentration, stiffness, and streaming potential were all approximately 25% that of calf articular cartilage. The frequency dependence of the dynamic stiffness and potential was similar to that of calf articular cartilage. Together, these results suggested the formation of a mechanically functional matrix.

Animals

[The evaluation of the measurement of serum fibronectin in pulmonary tuberculosis].

The investigation was carried out in 125 patients with pulmonary tuberculosis in different stages of evolution. The treatment was that granted, used in triple and/or quadruple scheme twice a week. In the greatest part of the patients the concentration of serum fibronectine (sFN) was followed in its dynamics. A reasonable increase (statistical average) of the sFN was found in the patients with tuberculosis (tbc), active at the first treatment. The values regressed slowly, parallel to the favourable evolution under treatment. In the chronic forms, values situated at the normal or at the inferior limit were recorded. They were probably due to the sum of factors often met in these patients: protein-caloric malnutrition, chronic alcoholism with afferent hepatopathies, nonspecific chronic bronchial suppurations. No significant correlation of the sFN concentration was noticed in relation to the radiologic extension of the lesions, to the structure of the chemotherapeutic regimen, or to age. There exists a large variability of the sFN concentration in tbc, both at the beginning and during chemotherapy. The sFN level is not enough for the assessment of the disease stage or evolution; for increasing its informational value, the concentration of the immune circulatory complexes (ICC) and the lymphocytic subsets T were investigated.

Adolescent

[Clinical, functional and hemodynamic course in patients with chronic bronchitis at the stage of chronic cor pulmonale].

Twenty seven patients, almost all chronic bronchitic, and with a "chronic cor pulmonale" according to the E. C. G., were followed clinically, radiologically and for E. C. G. and pulmonary functions, and also for the hemodynamics, during a minimum of 3 years, the average length of observation period being about 5 years. Twelve patients died during this observation time. Periods of right heart failure (R. H. F.) were frequent : 3.6 +/- 3.0 in average, slightly more frequent in the deceased patients than in the others. The average delay between the onset R. H. F. and death was of 49.3 +/- 30.8 months ; the survivors on average lived another 54.6 +/- 30.8 months after their first R. H. F. The mean pulmonary arterial pressure (PAP) was quite stable, going from 27.5 +/- 7.0 to 31.2 +/- 9.6 torr (an unsignificicant difference); in only 9 cases did the PAP increase of more than 5 torr during the observation period (acute attacks excepted). The PAP evolution was not significantly different in the deceased and the survivors. PAP worsening by steps after a fit of R. H. F. was observed in only 4 cases. Chronological variations of PAP were well correlated with those of Pao2 during the same period : r = -- 0.68, P less than 0.001. The hemodynamic evolution (PAP), that of the E. C. G. and the volume of the heart were reasonably parallel to the overall clinical evolution ; the E. C. G. evolution had the closest match with the overall clinical evolution (78% of cases). The E. C. G. enables only a late diagnosis of CCP but its evolution is very valuable for prognosis. Hemodynamic tests have a double value initially for diagnosis and later for the evolution.

Adult

Virulent Parasites Emerge in Hosts With Rising Temperatures.

Climate change is increasing the risk of emerging parasites. However, whether more virulent variants will spread during climate-driven outbreaks remains unclear. Here, we aimed to explore the short-term trajectory of parasite evolution-at the phenotypic and genomic scales-across environmentally relevant temperatures in a thermally mismatched host-parasite interaction. We experimentally evolved a wild parasitic bacterium (Leucobacter musarum), across the thermal range (20°C-30°C) and extremes (35°C) of Cabo Verde-the site of field collection-in a Caenorhabditis elegans host strain. Starting from a single bacterial isolate, we then tracked phenotypic and de novo genomic changes that arose across replicate populations following ten passages of experimental evolution. We found that at 25°C, warm for the host but an average temperature for the parasite, host-mediated selection favoured higher virulence and genomic diversification by the end of the experiment. At hot temperatures, towards the limit of host survival, virulence was maintained across all parasite populations. Parasites evolved at hot temperatures also displayed a latent virulence boost, deadlier once hosts experienced a heatwave. Patterns of molecular evolution were constrained to parallel changes in fewer loci at extreme temperatures. Our findings suggest that shifting environmental temperatures will leave phenotypic and genomic signatures on evolving parasites.

Animals

Spastic paraplegia associated with Addison's disease: adult variant of adreno-leukodystrophy.

Clinical and pathological features of an adult variant of adreno-leukodystrophy (ALD) are presented. A male with clinical and laboratory signs of Addison's disease (AD) developed at age 22 a slowly progressing paraplegia with slight sensory deficits in both legs and bladder and sphincter dysfunctions; he died at age 24 in an AD crisis. Autopsy revealed hyperplasia of lymphatic tissues, lymphocytic infiltrates in various organs including the CNS and adrenocortical atrophy with prominence of large ballooned, sometimes bizarre and occassionally striated cortical cells. CNS lesions consisted in incomplete demyelination of long tracts of brain stem and spinal cord with accentuation in the pyramical tracts; in these areas, perivascular cuffs of "epitheloid" histiocytic cells contained a strongly PAS-positive non-sudanophilic material. Electron microscopy demonstrated massive stroge of leaflet structures in perivascular histiocytes identical to the lamellar profiles previously described as specific for ALD. Some leaflets were found in close contact with compact lamellar arrays and with an electron-dense fingerprint material within astrocytes. In our case, the spastic paraplegia-AD syndrome which has been described previously in several clinical observations could be neuropathologically classified as an adult variant of ALD. Several differences to "classical" ALD occurring in young boys are stressed: the predominance of the endocrine disorder probably accounting for some of the perivascular lymphocyte infiltrates within the CNS; the absence of both clinical and pathological signs of diffuse cerebral involvement and the peculiar topistic pattern of CNS lesions and the very slow evolution of neurological signs paralleled by the absence of active sudanophilic demyelinating lesions. The possible mechanism of demyelination and the nature of the suggested metabolic defect in ALD are discussed. The ultrastructurally prominent leaflet structures may originate from myelin remnants, thus relating ALD to pathological storage of a myelin degradation product.

Addison Disease

Dynamic computed tomography of cerebral parenchymal tuberculomata.

The technique of intravenous dynamic cranial computed tomography has been applied to our patient population in Saudi Arabia in which parenchymal tuberculomata make up approximately 10-15% of all cerebral mass lesions. A spectrum of perfusion patterns was observed in tuberculosis progressing from presentation, through treatment, to resolution. These patterns reflect the microscopic vascular evolution of tuberculomata and parallel at least in part the effects of treatment. The method of dynamic scanning further demonstrates its value in improving the specificity of computed tomography in the evaluation of cerebral masses, thereby enhancing patient-beneficial triage.

Adolescent

Effect of prior exercise in Pi/PC ratio and intracellular pH during a standardized exercise. A study on human muscle using [31P]NMR.

Seven subjects underwent a standard localized exercise of calf muscles in order to investigate whether the metabolic exercise-induced steady-state, as revealed by the evaluation of inorganic phosphate/phosphocreatine ratio, depends on the conditioning of the muscle just prior to the exercise. The experimental protocols consisted of two separate experiments using first [31P]nuclear magnetic resonance spectroscopy and second (on 3 subjects) infrared oxyphotometry to respectively follow variation of energy metabolism and tissular deoxygenation. The exercise consisted of 240 successive plantar flexions (0.5 Hz frequency) against a high load equivalent to 80% of the maximal voluntary contraction. This exercise was accomplished before cold exercise and after warm exercise, a warming-up period bringing to approximately 50% of VO2max. The results showed that: (1) steady-state level of phosphate/phosphocreatine and intracellular acidosis was significantly lowered by warming-up; (2) cold and warm exercise steady-state of calculated adenosine diphosphate values were not significantly different; (3) cold exercise rapidly induced a high tissular deoxygenation that is not observed during warm exercise; and (4) time-constant of phosphocreatine resynthesis is lowered after warm exercise but the initial slope of time-evolution is not modified. Parallel experiments also showed that phosphate/phosphocreatine steady-state was not modified in comparison with warm exercise when the same power of exercise was reached by stepwise incrementation of the charge. From these results we postulate that a better tissue oxygenation due to a global or localized warming-up allows to reach the same mechanical performance with a lower decrease of PCr content, owing to a faster adjustment of oxidative metabolism during the transitional period.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate

Alkaline phosphatase positive lymphocytes (APPL) in man.

APPL are located in human lymph nodes in almost the same sites as in the laboratory rodents studied up to date. This means that their echotaxis is almost identical and may be an old phylogenetic heritage. But APPL may be found in man until puberty only; thereafter they disappear from all the lymphatic organs. At the age of 40 their depletion is perfected. This evolution of APPL is parallelized by thymus involution. Therefore we may strengthen the conclusion that APPL belong to the T-dependent lymphocytes and that all lymphocytes which really have visited the thymus acquire the enzymatic marker.

Adult

[A method for the determination of corroding factors of amalgams by electrical measurements].

The study describes a method for the determination of corrosion kinetics of amalgams from the buccal cavity by measuring initial and evolutive electrical potentials in parallel with an evaluation of clinical factors. It also deals with factors which might be improved in this connection. The method was applied experimentally in 125 cases with restoration therapy with silver amalgam, and a digital milivoltmeter for direct current was used, of 0.2% precision class with silver chloride electrodes to which two probes have been adapted. The values determined varied between--320 and--82 milivolts. The advantages as compared with previously used methods are the following: an electrical measurement of resistance to corrosion of amalgams, and improvement of factors which influence corrosion.

Corrosion

Complexity of the Rh antigen demonstrated by comparative tests using antisera of human and primate origins.

Comparative analysis of two antisera, one produced in chimpanzee and another of human origin, demonstrates the existence of the whole spectrum of antibodies directed against at least four, and possibly five, antigenic determinants connected with the Rh reactivity. Some of the determinants are shared by chimpanzee and human red cells, while others are restricted to one species only. Based on this study, it is suggested that both the human Rh(D)-positive type and its chimpanzee counterpart, the Rc-positive type, could be of common origin, while the negative types are the results of later, parallel events during the evolution.

Animals