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PubMed1980

[Value of the measurement of gases in the diagnosis of pleural effusion (author's transl)].

Determination of pH and measurement of pCO2 and pO2 have been systematically included in the study of 183 patients with pleural effusion. According to selective etiologic criteria the effusions were divided into four categories: those of cardiac origin (42), non-specific infectious (14), tuberculous (22) and neoplastic (20). A pH inferior to 6.30 seemed to be characteristic of non-tuberculous pleural effusion, and in these circumstances an associated pCO2 greater than 135 mm Hg and pO2 less than 21 mm Hg were noticed. Results in tuberculous and neoplastic cases were similar, pO2 being the only differential datum (pO2 less than 49 mm Hg and pO2 greater than 52 mm Hg, respectively). Overall results are compared to those obtained in the subgroup of pleural effusions of cardiac origin. Determination of pH, pO2 and pCO2 in pleural effusions may help to identified the etiology of this condition, specially when associated to analysis of other parameters of the aspirated fluid.

Carbon Dioxide↗

PubMed1983

Relationship of the biodisposition of the stereoisomers of nicotine in the central nervous system to their pharmacological actions.

The stereoisomers of nicotine were evaluated for their effectiveness in producing antinociception and altering spontaneous activity and Rotarod performance in rats. (-)-Nicotine was found to be 6, 15 and 30 times more active than its unnatural enantiomer, (+)-nicotine, in the spontaneous activity, Rotarod and antinociceptive tests, respectively. Biodispositional studies revealed that the time course (-)-[3H]nicotine closely paralleled the time course of effects on spontaneous activity and Rotarod performance but not antinociception, which suggested that multiple mechanisms were involved in the actions of nicotine. In addition, the distribution studies showed the brain and plasma levels of (-)-[3H]nicotine were higher than those of (+)-[3H] nicotine, which indicate that the pharmacological stereoselectivity of nicotine is less than originally determined. Finally, the greatest difference in the regional localization in brain of the stereoisomers was found in cerebral cortex, hippocampus and corpus striatum.

Analgesia↗

PubMed1981

Distinction of seventy-one cultured human tumor cell lines by polymorphic enzyme analysis.

A large collection of cultured human tumor cell lines was characterized for the phenotypes of 16 polymorphic enzyme loci: ACP1, ADA, AK1, ESD, FUCA, GLO1, GOT2, G6PD, ME2, PEPA, PEPB, PEPC, PEPD, PGD, PGM1, and PGM3 primarily to detect and monitor against cell line contamination. Among 100 highly characterized cell lines, 59 lines from different patients and 6 pairs of lines (each pair from the same patient's tumor) had unique phenotype combinations and were therefore presumed to be authentic, uncontaminated cell lines. Besides these 71 lines, the remaining 29 lines consisted of several small groups of two to three lines, each group having a different combination and being among the more frequent in the normal population. The 29 lines, therefore, were not suspected to be contaminants. Among unusual findings were the ME2 1 plus 2 phenotype determined for two bladder tumor lines, a G6PD A phenotype found in a line of Caucasian origin determined not to be a HeLa contaminant, and asymmetrical heterozygous phenotypes in several lines. Except for kidney tumor lines, there was no correlation of adenosine deaminase tissue isoenzymes between tumor lines and normal tissues of origin. For several enzymes significant deviations were found in proportions of the phenotypes observed in Caucasian cell lines from expected proportions on the basis of normal population data, indicating possible natural selection among these lines in tissue culture or among the patients of origin.

Cell Line↗

PubMed1995

[Is there an end to adolescence?--Observations from the ethnopsychoanalytic viewpoint].

Being an adult today does not mean anymore to have secure knowledge and routine at one's disposal, but rather being able to endure anxiety and uncertainty in culture. In the course of the process of civilization youth has more and more become the model and embodiment of a dynamic, ever-changing culture. As a consequence of abolishing initiation rituals, which originally determined the transition to adulthood, adolescents today must develop their own strategies in order to relate chaos and order to each other. The antagonism between family and culture plays a central role here: The individual must be able to personify two aggregate states as it were, that is being firm in the family and being fluid in culture. Today adolescence only ends inside the family when the individual takes on a parent role, but in the cultural area we should remain adolescents all of our lives, in order to muster the creativity necessary for a changing culture.

Adaptation, Psychological↗

PubMed1994

Comparative evaluation of body composition methods and predictions, and calculation of density and hydration fraction of fat-free mass, in obese women.

The objective of this study was to apply a three-component model of body composition to a group of obese women in order to (a) establish the relative value of a number of readily available prediction equations by comparison of the extent of agreement between these predictions and body composition estimated by the model and other reference methods and (b) evaluate density and hydration of fat-free mass. Estimation of body composition was carried out by reference methods and prediction equations and the usefulness of these prediction equations for application specifically to obese women was evaluated. The subjects were 15 obese, otherwise healthy, Caucasian women (body mass index > 30kg/m2 and body fat > 40% of body weight, as originally determined using densitometry). Body composition was estimated using three established reference methods (deuterium dilution which primarily measures total body water, densitometry for body fat and fat-free mass and total body potassium) and the three component model constructed from deuterium dilution and densitometry. Density and hydration fraction of the fat-free mass were calculated from appropriate values obtained as integral parts of the three-component model. In addition, body composition was predicted from various prediction equations incorporating weight and height (some of which include a factor for age), from a number of prediction equations utilizing different terms involving the same whole-body bio-electrical impedance measurement and from measurements of skinfold thickness and near infrared interactance. The extent of agreement between methods was assessed using bias and 95% limits of agreement. Mean density of fat-free mass was found to be 1.104 kg/l (s.d. 0.006kg/l) with a range of 1.093 to 1.117 kg/l, and mean hydration fraction was 0.712 (s.d. 0.016) with a range of hydration from 68.2% to 75.1% (all values were calculated from the three-component model). In general, the reference methods (densitometry, deuterium dilution, the three-component model and total body potassium) demonstrated better agreement with each other than with the prediction methods or equations. In these obese women, skinfold thickness measurements are apparently less reliable (large bias and 95% limits of agreement) than in the lean subjects of a variety of other studies. A majority of interpretations of weight and height measurements and predictions incorporating impedance/resistance measurements are apparently not applicable to this group of obese women, due to large values for both bias and 95% limits of agreement.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

PubMed1994

Deoxyribonucleotides are maintained at normal levels in a yeast thioredoxin mutant defective in DNA synthesis.

Deletion of both thioredoxin genes TRX1 and TRX2 of Saccharomyces cerevisiae reduces the rate of DNA replication. This observation, originally determined by flow cytometry, was confirmed by radiochemical labeling of synchronized cultures. Since thioredoxin is a hydrogen donor to ribonucleotide reductase, a priori the inhibition of DNA synthesis was predicted to be caused by a reduction in the deoxyribonucleotide pools. However, the levels of TTP, dCTP, dATP, and dGTP were either unchanged or slightly greater in the thioredoxin mutant (3.2, 0.91, 1.4, and 1.21 pmol/10(6) cells, respectively) versus the wild-type culture (2.5, 0.91, 1.0, and 0.68 pmol/10(6) cells, respectively). An impact on ribonucleotide reduction was seen by an increased accumulation of RNR1 and RNR2 transcripts in the thioredoxin mutant (4.3- and 6.8-fold, respectively). Increased RNR expression did not reflect a general response of the DNA replication machinery. POL1 (DNA polymerase I) and CDC8 (thymidylate kinase) transcription were unaltered, while histone H2B transcripts actually decreased by half. Two alternative models incorporating these results are discussed. One suggests that thioredoxin reduces a multiprotein complex channeling nucleotides to the replication apparatus. The second proposes that thioredoxin regulates the tempo of DNA replication directly by activating a component of the replication machinery.

DNA Replication↗

PubMedDate not supplied

[Segments initiating replication of the dihydrofolate reductase domain and the DNA fragment DARC146 interact with the same nuclear proteins].

Comparison analysis was made of the putative replication origin DARC146 and the origin determined in the DNFR domain of CHO cells. We failed to observe extensive homology between these two sequences. However, several short (8-10 bp) areas of homology were identified. Some of them are binding sites for nuclear proteins. As shown by GM and competition experiments, both origins contain high-affinity binding sites for the transcription-replication factor Oct-1 and for two unknown nuclear factors. The two unknown nuclear factors bound to TCTCTTA and CACTTAG nucleotides. The binding sites for these proteins are located at a short distance from each other. This fact suggests interaction between these polypeptides. Measurement of DNA-binding activity of Oct-1 during the cell cycle of proliferating hepatocyte demonstrated that the binding activity of Oct-1 protein increased before initiation of DNA synthesis. The results of this report suggest that Oct-1 and two other nuclear proteins participate in the regulation of mammalian DNA replication. The results published early indicated the presence of an unusual DNA structure (bent DNA) in both origins under study. We suggest that these common elements of the origins regulate their activation.

Animals↗

PubMed1993

Antigenic characterization of human isolates of cryptosporidia.

Isolates of cryptosporidia from immunodeficient patients and from immunocompetent children suffering from diarrhoea were sources for preparation of antigens. Altogether, antigens from 21 isolates were obtained, 19 from children and 2 from AIDS patients. With one exception, all children were under 4 years old and most of them were between 1 and 2 years old. The probable source of infection was found in 11 cases. In 8 cases, as well as in both AIDS patients, the source of infection was not determined. The same groups of persons and the control group of healthy blood donors were examined serologically using ELISA with the antigen of bovine origin and positive sera were used for following experiments. Soluble and membrane-enriched antigens from oocysts were compared using polyacrylamide gel electrophoresis and electroimmunotransfer blots developed by human immune sera. While no differences were recorded in soluble antigens, two of the membrane-enriched antigens were missing (15.5 and 33 kD bands). While all isolates with a pattern typical for Cryptosporidium parvum were infective for neonatal mice, both isolates with missing bands were not infective for newborn mice in repeated experiments. The first of them was infective for chickens and was originally determined to be Cryptosporidium baileyi (Ditrich et al. 1991). However, the antigenic pattern differs from pattern of this species. The second isolate was infective for guinea pigs and its species classification remains uncertain.

Adolescent↗

PubMed1994

Validating the TMJ scale in a national sample of 10,000 patients: demographic and epidemiologic characteristics.

The accuracy and reliability of the TMJ Scale were originally determined in cross-validation studies on large, research-based patient samples. It had been assumed that the demographic characteristics and test responses of these research-based samples would be representative of the clinical population in which the TMJ Scale would ultimately find use. The present study on more than 10,000 patients that were evaluated for temporomandibular disorders in clinical practice demonstrates that the test scores, demographic variables, and the patterns of symptom severity that characterize the original TMJ Scale research sample accurately represent the general temporomandibular disorder patient population in which the TMJ Scale is now being used. The results suggest a high degree of confidence in the clinical efficacy of this assessment tool. The overall symptom severity of temporomandibular disorders was found to be normally distributed in the patient population. Women with temporomandibular disorders report a higher level of severity of all physical and psychological symptoms than men. This may explain the high female-to-male ratio in patients seeking treatment. However, a higher percentage of male temporomandibular disorder patients has clinically significant psychological and stress-related problems than do women. The severity and prevalence of symptoms associated with joint dysfunction and range of motion limitation are lower in older age groups, and the overall symptom severity of temporomandibular disorders is not higher in older age groups. However, the severity and prevalence of symptoms associated with joint dysfunction are greater in groups in which temporomandibular disorders have existed for longer durations, although pain levels do not follow this trend. There is also an association between time duration of the temporomandibular disorder and the severity of psychological problems and chronicity. Patients with chronic problems are symptomatically more impaired than those with acute problems.

Acute Disease↗

PubMed1977

Embryogeneic cell type, organ site sequence specificity in human cancers.

An extensive series of cross-hybridization studies were carried out with the DNA-RNA molecular hybridization technique. Molecular 70 S [3H]DNA probes synthesized from human central nervous system, gastrointestinal, pulmonary, and prostatic carcinomas were hybridized to cytoplasmic RNA's isolated from cancers of virtually all organ sites of the human body. Results indicated sequence homology between cancers of the same organ or cell type but not with cancers of different cell types. Thus cell types based on embryological origins determine the organ site specificity of the involved sequences. The designation of 70 S [3H]DNA denotes those [3H]DNA's that were copied off the template 70 S RNA, as distinguished from total [3H]DNA product, which includes all DNA's synthesized. It does not necessarily follow nor is it to be inferred that the 70 S [3H] DNA thus designated contains the full complement of the sequences found in the 70 S RNA template.

Base Sequence↗

PubMedDate not supplied

Serum aminotransferase levels and histological disease in chronic hepatitis C.

The reliability of serum aminotransferase (ASAT and ALAT) levels, currently used in deciding on performing liver biopsy and to assess interferon therapy in chronic hepatitis C has been questioned. In Belgium, interferon therapy is actually only reimbursed for treatment of chronic hepatitis C when serum aminotransferase levels are more than twice the upper limit of normal. The aim of the present study was to assess the relationship between serum aminotransferase levels and histological severity of chronic hepatitis C. Sixty-seven liver biopsies from 51 different patients with chronic hepatitis C and presenting with elevated ASAT and/or ALAT levels, were retrospectively evaluated using the original terminology (minimal hepatitis, chronic persistent hepatitis, chronic active hepatitis, cirrhosis), the Knodell score and the components of the Bianchi-Gudat score, where grading (portal inflammation, piecemeal necrosis, intra-acinar necrosis and inflammation) and staging components (fibrosis/ cirrhosis) are quantitated separately. The correlation between amino-transferase levels measured at or near to the biopsy date and histological criteria were evaluated using Spearman's rank correlation. About one third of the patients, including patients with chronic active hepatitis and cirrhosis, presented with ASAT and ALAT levels less than twice the upper limit of normal. ASAT levels correlated with originally determined histological severity, the numerical Knodell score and the numerical scores for piecemeal necrosis, for intra-acinar necrosis and inflammation and for fibrosis in the Bianchi-Gudat score. ALAT levels correlated only with intra-acinar necrosis and inflammation. It is concluded that limiting interferon therapy to patients with aminotransferase levels over twice the upper limit of normal excludes a large proportion of patients from potentially curative treatment. ASAT levels are more useful than ALAT to assess the histological severity of the disease, probably because this mitochondrial enzyme is present in higher quantities in the liver as compared to the cytosolic ALAT, and is more released when tissue damage is more severe.

Adult↗

PubMed1997

Kinetics of central nervous system microglial and macrophage engraftment: analysis using a transgenic bone marrow transplantation model.

To determine the kinetics of tissue macrophage and microglial engraftment after bone marrow (BM) transplantation, we have developed a model using the ROSA 26 mouse. Transplanted ROSA 26 cells can be precisely identified in recipient animals because they constitutively express beta-galactosidase (beta-gal) and neomycin resistance. B6/129 F2 mice were irradiated and transplanted with BM from ROSA 26 donors and their tissues (spleen, marrow, brain, liver, and lung) examined at various time points to determine the kinetics of engraftment. Frozen sections from transplanted animals were stained histochemically for beta-gal to identify donor cells. At 1, 2, 6, and 12 months posttransplantation, 98% to 100% of granulocyte-macrophage colonies were of donor (ROSA 26) origin determined by beta-gal staining and by neomycin resistance. Splenic monocytes/macrophages were 89% donor origin by 1 month confirming quick and complete engraftment of hematopoietic tissues. At this time, only rare ROSA 26 tissue macrophages or microglia were observed. Alveolar macrophage engraftment was evident by 2 months and had increased to 61% of total tissue macrophages at 1 year posttransplantation. The kinetics of liver Kupffer cell engraftment were similar to those seen in the lung. However, donor microglial engraftment remained only 23% of total microglia at 6 months and increased to only 30% by 1 year. Also, donor microglia were predominantly seen at perivascular and leptomeningeal, and not parenchymal, sites. The data show that microglia derive from BM precursors but turn over at a significantly slower rate than other tissue macrophages. No clinical or histological graft-versus-host disease was observed in the recipients of ROSA 26 BM. These kinetics may impact strategies for the gene therapy of lysosomal storage diseases. Because individual donor cells can be identified in situ, the ROSA 26 model should have many applications in transplantation biology including studies of homing and differentiation.

Animals↗

PubMed1997

S phase damage sensing checkpoints in mammalian cells.

Mammalian cells have evolved multiple responses for dealing with DNA damage. One response is to acutely downregulate DNA synthesis at the initiation step. Essentially nothing is known about the initial signal that activates this SDS pathway or the macromolecules involved in transducing the signal into the final inhibitory step at origins. Determining whether any radiation induced changes in known proteins involved in cell cycle regulation or in other signal transduction pathways are primary or secondary responses to DNA damage constitutes a major challenge to identifying members of the pathway. It may turn out to be easier to identify the final mediator in the pathway, namely the protein(s) whose interaction with origins is ultimately affected by radiation. Hopefully, mutations in SDS genes in genetically tractable systems such as S cerevisiae or Schizosaccharomyces pombe will allow the identification of homologous genes in mammals. Most tumour cells are TP53 negative, and yet it is not clear that TP53 status influences radiation sensitivity. The SDS pathway may therefore represent an important protective mechanism that stands in the way of effective tumour cell killing by radiation therapy. It is hoped that an understanding of this pathway will provide opportunities for developing novel antineoplastic targets and/or radiation sensitizers.

Animals↗

PubMed1997

Redox active disulfides: the thioredoxin system as a drug target.

Thioredoxin, and particularly extracellular thioredoxin, presents an attractive target for developing novel agents to treat cancer. Our studies have involved the examination of a series of alkyl 2-imidazolyl disulfides as inhibitors of the growth-stimulatory activity of the thioredoxin system. We originally determined the disulfides to be weak reversible inhibitors of thioredoxin reductase. Subsequently, we have shown that alkyl 2-imidazolyl disulfides interact directly with thioredoxin, thioalkylating critical cysteine residues or causing dimerization of the protein leading to its loss of biological activity. One of the analogues that binds to thioredoxin, 1-methylpropyl 2-imidazolyl disulfide (IV-2), selectively inhibits the thioredoxin-dependent growth of tumor cells in culture and has antitumor activity against MCF-7 and HL-60 tumors in vivo. Our work involves the development of a parallel combinatorial synthetic method to produce a large number of disulfide analogues at one time. These analogues, which differ sterically, electronically, and physically, were produced in a 96-well plate. The biological activity of these analogues was evaluated, also in the 96-well plate format. This rapid method of evaluating biological activity is a means to identify agents with specificity for inhibition of the thioredoxin system, and may provide novel antitumor agents with activity against solid tumor cancers.

Animals↗

PubMed1998

[The value of endoscopic ultrasonography in the study of submucosal tumors of the digestive tract].

Twenty-one consecutive patients with 24 possible submucosal lesions of the digestive tract were studied. Endoscopic ultrasonography (EUS) differentiated between 17 true positive submucosal tumors and 3 true negative extrinsic compressions. False positives were interpreted in 3 cases and in one patient no lesion was echoendoscopically observed (false negative). The sensitivity was 94%, the specificity 50% and the positive and negative predictive values were 82% and 75%, respectively. In conclusion, EUS may be the method of choice for the study of submucosal tumors since it allows visualization of the five layers of the wall of the digestive tract in which a tumor may originate, determination of its sonographic features, depth and exact size, in addition to the invasion of neighboring organs. Moreover, EUS may aid in collecting material for cytology and microscopy by fine needle aspiration puncture (FNAP) by EUS.

Adult↗

PubMed1998

[Residential colonization of orbital complex "Mir" environment by penicillium chrysogenum and problem of ecological safety in long-term space flight].

Results of many years of the survey of highly specific evolution of quantitative and species composition of microflora of the MIR environment are reviewed. Analysis of the data enabled listing of microorganisms-declinous fungi with the ability of residential colonization of structural materials of the interior and equipment of habitable modules of the space station. Results of the studies of variability and level of similarity/affinity on the basis of DNA, polymorphism of strains isolated in space flight, convincingly confirmed this characteristic in the Penicillium chrysogenum cultures. In view of the common origin determined from the signs of genetic alliance, the P. chrysogenum strains isolated on MIR in 1995 can be considered descendants of the cultures found at the beginning of the MIR operation. This ecological expansion of P. chrysogenum in the space station environment gains in prominence due to the fact that representative of this particular species known for its active biodestructive nature were, as a rule, detected in the areas where structural materials of the SALYUT and MIR space stations incurred biological degradation.

Colony Count, Microbial↗

PubMed1997

Current migration to Europe.

"In this...article, we concentrate our attention on migration from the Mediterranean region and Sub-Saharan Africa (South-North migration) and from Central and Eastern Europe (East-West migration).... After briefly discussing history and causes of these migration flows, we will address where European immigration stands to date. In conclusion we discuss what is likely to happen within the Europe-centred migration system in the foreseeable future."

Africa↗