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PubMed1995

Hepatic granulomatosis in a patient with Graves' disease.

We report a case of granulomatous hepatitis in a patient with hyperthyroidism resulting from Graves' disease. A 30-year-old man presented with massive weight loss, jaundice, tachyarrhythmia and goitre. Liver function tests showed mild cytolysis and cholestasis and massive hyperbilirubinaemia. The echogram of liver and bile ducts was normal and no infection was found. A liver biopsy revealed a mixed cytolytic and cholestatic hepatitis with intralobular epithelioid granulomas. No specific cause was identified, and sarcoidosis and primary biliary cirrhosis were ruled out. The outcome was favourable with antithyroid therapy and short-term glucocorticoid therapy, and the patient was totally free of symptoms after 2 years. To our knowledge, this is the first case of granulomatous hepatitis to be reported in association with Graves' disease. The clinical evolution of the liver disease paralleled the evolution of hyperthyroidism.

Adult↗

PubMed1998

Parallel and divergent genotypic evolution in experimental populations of Ralstonia sp.

Genetic rearrangements within a population of bacteria were analyzed to understand the degree of divergence occurring after experimental evolution. We used 18 replicate populations founded from Ralstonia sp. strain TFD41 that had been propagated for 1,000 generations with 2,4-dichlorophenoxyacetic acid (2,4-D) as the carbon source. Genetic divergence was examined by restriction fragment length polymorphism analysis of the incumbent plasmid that carries the 2,4-D catabolic genes and by amplification of random regions of the genome via PCR. In 18 evolved clones examined, we observed duplication within the plasmid, including the tfdA gene, which encodes a 2,4-D dioxygenase that catalyzes the first step in the 2,4-D catabolic pathway. In 71 of 72 evolved clones, a common 2.4-kb PCR product was lost when genomic fingerprints produced by PCR amplification using degenerate primers based on repetitive extragenic palindromic (REP) sequences (REP-PCR) were compared. The nucleotide sequence of the 2.4-kb PCR product has homology to the TRAP (tripartite ATP-independent periplasmic) solute transporter gene family. Hybridization of the 2. 4-kb REP-PCR product from the ancestor to genomic DNA from the evolved populations showed that the loss of the PCR product resulted from deletions in the genome. Deletions in the plasmid and presence and/or absence of other REP-PCR products were also found in these clones but at much lower frequencies. The common and uncommon genetic changes observed show that both parallel and divergent genotypic evolution occurred in replicate populations of this bacterium.

Chlorophenols↗

PubMed1987

The evolution of antibiotic production and public health problems.

Antibiotic evolution is closely paralleled by the evolution of bacterial resistance. Prior to wide usage of penicillin G, resistance to beta-lactam antibiotics as a consequence of beta-lactamase production had been recognized, and has been an increasing clinical problem ever since. Discovery of antibiotics other than beta-lactams, such as macrolides, tetracyclines and aminoglycosides, has also resulted in the eventual selection of bacteria resistant to these agents. Synthesis of novel beta-lactam derivatives from 6-APA, such as methicillin and isoxazolyl penicillins, resistant to staphylococcal beta-lactamase, overcame the clinical problem of penicillin-resistant S. aureus. Likewise, the isolation of cephamycins and monobactams, and further exploitation of the cephalosporin nucleus, led to the development of derivatives which display a high degree of stability to a wide range of gram-positive and gram-negative bacterial beta-lactamases, thus rendering organisms producing these enzymes susceptible to these agents. Analogous modification of the penicillin nucleus, to give 6 alpha-substituted penicillins, also resulted in derivatives with exceptional stability to beta-lactamases. An alternative approach to the problem of beta-lactamase was the isolation or synthesis of substances able to inhibit the activity of enzymes, thus protecting the unstable beta-lactams from inactivation by beta-lactamase. In this way the activity of beta-lactamase-labile agents was effectively restored against a wide range of beta-lactamase-producing bacterial pathogens. The wide diversity of new antibacterial agents, together with an increasing knowledge and understanding of mechanisms of resistance, indicates that further advances against resistant bacterial pathogens is ensured.

Anti-Bacterial Agents↗

PubMed2025

Genome-wide Parallelism Underlies Rapid Freshwater Adaptation Fueled by Standing Genetic Variation in a Wild Fish.

A fundamental focus of ecological and evolutionary biology is determining how natural populations adapt to environmental changes. Rapid parallel phenotypic evolution can be leveraged to uncover the genetics of adaptation. Using population genomic approaches, we investigated the genetic architecture underlying rapid parallel freshwater adaptation of Neosalanx brevirostris by comparing four freshwater-resident populations with their common ancestral anadromous population. We demonstrated that the rapid parallel adaptation to freshwater followed a complex polygenic architecture and was characterized by genomic-level parallelism, which proceeded predominantly through repeated selection on the preexisting standing genetic variations. Frequencies of the genome-wide adaptive standing variations were moderate in the ancestral anadromous population, which had pre-adapted to fluctuating salinities. Relatively large allele frequency shifts were observed at some adaptive single-nucleotide polymorphisms (SNPs) during parallel adaptation to freshwater environments, with a large fraction of freshwater-favored alleles being fixed or nearly fixed. These adaptive SNPs were involved in multiple biological functions associated with osmoregulation, immunoregulation, locomotion, metabolism, etc., which were highly consistent with the polygenic architecture of adaptive divergence between the two ecotypes involving multiple complex physiological and behavioral traits. This work provides insight into the mechanisms by which natural populations rapidly evolve to changes in the environment and highlights the importance of standing genetic variation for the evolutionary potential of populations facing global environmental changes.

Animals↗

PubMed1994

A parallel between development and evolution: germ cell recruitment by the gonads.

In gonad-bearing animals gametogenesis can be divided into three main phases. During embryonic development the primordial germ cells move towards the gonadal primordia. A long, intra-gonadal phase follows during which the germ cells grow and differentiate. Mature germ cells are finally released from the gonads and brought to the exterior. Thus, germ cells are successively motile, non-motile and motile again. This complex life history is given here a simple evolutionary interpretation. The basic assumption is that primitive Metazoa already had germ cells, but no gonads to harbour them. Higher animals acquired gonads, which sequestered the germ cells, thus creating the temporary confinement experienced by germ cells in most present-day Metazoa. This evolutionary scheme may explain why several steps of germ cell differentiation are totally or partially independent of the gonads. These steps presumably existed in primitive, gonad-free Metazoa, and conserved their autonomy in higher animals.

Animals↗

PubMed1984

Human alcohol dehydrogenase: structural differences between the beta and gamma subunits suggest parallel duplications in isoenzyme evolution and predominant expression of separate gene descendants in livers of different mammals.

Human alcohol dehydrogenase (ADH; alcohol:NAD+ oxidoreductase, EC 1.1.1.1) occurs in multiple forms, which exhibit distinct electrophoretic mobilities and enzymatic properties. The homogeneous isoenzymes beta 1 beta 1 and gamma 1 gamma 1 were isolated from livers of Caucasians with "typical" ADH phenotype by double ternary complex affinity chromatography and ion exchange chromatography. The differences between the beta 1 and gamma 1 subunits were determined by structural analysis of all tryptic peptides from the carboxymethylated proteins. The human beta 1 and gamma 1 chains differ at 21 of the 373 positions (5.6%). Ten tryptic peptides account for the differences. All residue substitutions are compatible with one-base mutations and result in largely unaltered properties, but five lead to charge differences. Sixteen substitutions are at positions corresponding to the catalytic domain of the well-known horse enzyme; five correspond to the coenzyme-binding domain. Substitutions adjacent to important regions may correlate with differences in coenzyme binding, substrate specificities, and active-site relationships. The residue replacements between the beta 1 and gamma 1 subunits of human ADH are not identical to the known substitutions between ethanol-active (E) and steroid-active (S) subunits of horse ADH. Thus, the duplication leading to human beta 1 and gamma 1 subunits is separate and different from that leading to equine E and S subunits. Both duplications are likely to have occurred after the ancestral separation of human and equine ADH. Of the 21 residues that are different between beta 1/gamma 1, 13 in gamma 1 but only 6 in beta 1 are identical to those of the horse E chain. This suggests a closer relationship between gamma 1 and E, although beta 1 in man and E in the horse are the subunits recovered in highest yield from liver ADH preparations. Consequently, in these two mammalian species, relative activities of genes for an isoenzyme family appear to be different.

Alcohol Dehydrogenase↗

PubMedDate not supplied

Michigan's fisheater cohorts: a prospective history of exposure.

Interest in environmental contaminants and their effect on human health emerged as a primary focus in the 1970s following the discovery of significant levels of mercury, dichloro diphenyl trichloroethane (DDT), and polychlorinated bihpenyls (PCBs) in recreationally caught Great Lakes fish. In response to these findings, the Michigan Department of Public Health, in 1971, initiated a series of "fisheater" cohort studies. These studies continue to be conducted today. The evolution of human exposure assessment by serum PCB determination parallels the evolution of more precise and sensitive analytical laboratory procedures over the past 25 years. Early work quantitated PCB with Aroclor 1254 standards. By 1980, the Webb and McCall packed-column method (Webb and McCall, 1972, 1973), which quantitates total PCB with Aroclor 1016 and 1260 standards, had gained the Association of Official Analytical Chemists (AOAC) approval and became the accepted method. This method was used in the 1978-1980 Michigan Great Lakes Fisheater Study, the first sizable study of this kind in the nation. The study confirmed that fisheaters had significantly more exposure (median 21.4 ppb vs 6.6 ppb) than controls. Toxicology studies have indicated the need to quantitate individual PCB congeners, in order to correlate exposure with possible toxicological and health outcomes. Today, capillary column gas chromatography and gas chromatography/mass spectrometry are used to search for trace components of the total PCB dose (Mullen et al., 1984). Because of the legacy of the earlier analytical data, Michigan also continues to conduct packed-column analysis for longitudinal comparisons. The Michigan fisheater study database and registry provide a significantly exposed and historic foundation for research testing health outcome hypotheses.

Cohort Studies↗

PubMed1994

Perspectives on interactions with QA--the regulatory perspective.

It has been my experience that the quality assurance unit (QAU) normally serves as the facility point-of-contact with the agency on matters relating to a Good Laboratory Practice (GLP) compliance inspection. The QAU usually receives the notification letter, does most of the coordinating for the GLP inspection, and often bears the criticism for deficiencies found during the inspection. In general, as inspectors, we have found it difficult to get management to show any interest in the inspection and, in many facilities, have been forced to communicate almost entirely with the QAU. The evolution of the relationship between regulators and the QA community, which parallels the evolution of the image of quality assurance personnel from inexperienced technicians to recognized professionals, is discussed. Also discussed are both typical and atypical examples of interaction between government inspectors and quality assurance units.

Facility Regulation and Control↗

PubMed1999

Evolution of the carabid ground beetles.

The phylogenetic relationships of the carabid ground beetles have been estimated by analysing a large part of the ND5 gene sequences of more than 1,000 specimens consisting of the representative species and geographic races covering most of the genera and subgenera known in the world. From the phylogenetic analyses in conjunction with the mtDNA-based dating, a scenario of the establishment of the present habitats of the respective Japanese carabids has been constructed. The carabid diversification took place ca. 40 MYA as an explosive radiation of the major genera. During evolution, occasional small or single bangs also took place, sometimes accompanied by parallel morphological evolution in phylogenetically remote as well as close lineages. The existence of silent periods, in which few morphological changes took place, has been recognized during evolution. Thus, the carabid evolution is discontinuous, alternatively having a phase of rapid morphological change and a silent phase.

Animals↗

PubMed2024

Repeated evolution on oceanic islands: comparative genomics reveals species-specific processes in birds.

Understanding the interplay between genetic drift, natural selection, gene flow, and demographic history in driving phenotypic and genomic differentiation of insular populations can help us gain insight into the speciation process. Comparing patterns across different insular taxa subjected to similar selective pressures upon colonizing oceanic islands provides the opportunity to study repeated evolution and identify shared patterns in their genomic landscapes of differentiation. We selected four species of passerine birds (Common Chaffinch Fringilla coelebs/canariensis, Red-billed Chough Pyrrhocorax pyrrhocorax, House Finch  Haemorhous mexicanus and Dark-eyed/island Junco Junco hyemalis/insularis) that have both mainland and insular populations. Changes in body size between island and mainland populations were consistent with the island rule. For each species, we sequenced whole genomes from mainland and insular individuals to infer their demographic history, characterize their genomic differentiation, and identify the factors shaping them. We estimated the relative (Fst) and absolute (dxy) differentiation, nucleotide diversity (π), Tajima's D, gene density and recombination rate. We also searched for selective sweeps and chromosomal inversions along the genome. All species shared a marked reduction in effective population size (Ne) upon island colonization. We found diverse patterns of differentiated genomic regions relative to the genome average in all four species, suggesting the role of selection in island-mainland differentiation, yet the lack of congruence in the location of these regions indicates that each species evolved differently in insular environments. Our results suggest that the genomic mechanisms involved in the divergence upon island colonization-such as chromosomal inversions, and historical factors like recurrent selection-differ in each species, despite the highly conserved structure of avian genomes and the similar selective factors involved. These differences are likely influenced by factors such as genetic drift, the polygenic nature of fitness traits and the action of case-specific selective pressures.

Animals↗

PubMed1994

Bioenergetics: the evolution of molecular mechanisms and the development of bioenergetic concepts.

Possible routes for the evolution of cell energetics are considered. It is assumed that u.v. light was the primary energy source for the precursors of the primordial living cell and that primitive energetics might have been based on the use of the adenine moiety of ADP as the u.v. chromophore. It is proposed that the excitation of the adenine residue facilitated phosphorylation of its amino group with subsequent transfer of a phosphoryl group to the terminal phosphate of ADP to form ATP. ATP-driven carbohydrate synthesis is considered as a mechanism for storing u.v.-derived energy, which was then used in the dark. Glycolysis presumably produced compounds like ethanol and CO2, which easily penetrate the membrane and therefore were lost by the cell. Later lactate-producing glycolysis appeared, the end product being non-penetrant and, hence, retained inside the cell to be utilized to regenerate carbohydrates when light energy became available. Production of lactate was accompanied by accumulation of equimolar H+. To avoid acidification of the cell interior, an F0-type H+ channel was employed. Later it was supplemented with F1. This allowed the ATP energy to be used for 'uphill' H+ pumping to the medium, which was acidified due to glycolytic activity of the cells. In the subsequent course of evolution, u.v. light was replaced by visible light, which has lower energy but is less dangerous for the cell. It is assumed that bacteriorhodopsin, a simple and very stable light-driven H+ pump which still exists in halophilic and thermophilic Archaea, was the primary system utilizing visible light. The delta mu-H+ formed was used to reverse the H(+)-ATPase, which began to function as H(+)-ATP-synthase. Later, bacteriorhodopsin photosynthesis was substituted by a more efficient chlorophyll photosynthesis, producing not only ATP, but also carbohydrates. O2, a side product of this process, was consumed by the H(+)-motive respiratory chain to form delta mu-H+ in the dark. At the next stage of evolution, a parallel energy-transducing mechanism appeared which employed Na+ instead of H+ as the coupling ion (the Na+ cycle).(ABSTRACT TRUNCATED AT 400 WORDS)

Adenine↗

PubMed1986

Evolution of cell and chromosome structure in eukaryote.

The analysis of the data so far available indicates that eukaryotic chromosome with splicing characteristics appeared quite early in evolution possibly parallel and not sequential to the prokaryotic system. The endosymbiotic origin of the eukaryotic cell involved a primitive undifferentiated unicellular eukaryote and a photosynthetic or non-photosynthetic microbe. Certain regulatory genes of extra-cellular organelles were transferred later through molecular hybridization to the nucleus. The evolution of multicellularity and sexual reproduction led to the origin of innumerable eukaryotic forms in the late precambrian period. This new concept of the author can account for the evolution of complex eukaryotic chromosome and harmonious functioning of extra-cellular organelles with the nucleus. The concept also explains the sudden spurt of innumerable eukaryotic fossils at the early palaeozoic era.

Animals↗

PubMed1979

[Symptomatic arterial hypertension in lupus nephropathy].

Sixty six patients with lupus nephropathy with hypertonic syndrome are examined. In patients with latent (inactive) lupus glomerulonephritis hypertonic syndrome developed 3--8 months after the initiation of the corticosteroid treatment, advancing with fluctuations, in some of the patients the arterial pressure being normalized after the discontinuation of that treatment. In patients with chronic active lupus glomerulonephritis without nephrotic syndrome, the hypertension develops before the initiation of the corticosteroid treatment, fluctuating at the beginning, and gradually assumes a stable character 3--5 months after the beginning of such treatment, sometimes with a malignant course and rapid development of renal insufficiency. The hypertonic syndrome advances most severely and malignantly in chronic lupus glomerulonephritis with nephrotic syndrome and is resistant to the active antihypertensive treatment. In 18, out of 25, such patients, the hypertonic syndrome is manifested in parallel with nephropathy before the inclusion of the cortocosteroid treatment. The grave and malignant course of the hypertonic syndrome is associated with the peculiarities of the clinical form and histomorphological type of that lupus nephropathy. In the patients with nephrosclerosis, the hypertonic syndrome is with a gradually progressing evolution, in parallel with the progress of the renal insufficiency.

Adolescent↗

PubMed1983

[Characteristics of testosterone binding to plasma proteins during the sexual cycle in a seasonally-reproductive animal, the male viviparous lizard].

Plasma testosterone binding activity was determined by an equilibrium dialysis method in the male of Lacerta vivipara during the annual cycle of activity (from March to September). Capacity showed significant variations during the sexual cycle although affinity remained constant. The variations of capacity were then compared with plasma testosterone levels measured by radioimmunoassay and plasma proteins content measured by the Lowry method. The three parameters showed parallel seasonal evolution except in May-June when binding activity increased although plasma testosterone and protein levels fell. The physiological meaning of this conspicuous phenomenon is discussed=an active mechanism of strengthening of the atrophy of accessory sexual organs is hypothesized. Furthermore, the increase of the binding activity which occurs in autumn and is parallel to the levels of testosterone must prevent these accessory organs from a full resumption of activity before the retreat since the lizard is a hibernating animal. These results emphasize the key role played by specific plasma binding proteins in the modulation of steroid hormone action.

Animals↗

PubMed1985

[Angiolymphoid hyperplasia with eosinophilia. Extensive form associated with thrombopenic purpura].

The authors report a case, on a 59-year-old female patient, of angiolymphoid hyperplasia with eosinophilia (AHE) associated to a thrombopenic purpura (TP) of which the evolution is parallel. The clinical aspect is made of sub-cutaneous nodules of various sizes (1 or 2 cm on an average) and of more superficial, erythematous, sometimes telangiectatic, pseudo-angiomatous nodules. There are (about) 25 nodules, located on the face, the neck, the arms and the thorax, sometimes pruriginous: the rest of the examination is negative excepting axillary and inguinal small size lymph nodes and of a dermographism. The anatomopathological examination in optical microscopy, shows a dermo-epidermal lymphocytic infiltrate with which mingle numerous eosinophilic leucocytes. The dermal vessels are very altered, with a swelling endothelium and a proliferation of endothelial and perithelial cells filling up in large part the vascular section. The biological investigation show essentially: a slight and altering hypereosinophilia (between 500 and 800/mm3); a low amount of blood-platelets (between 95,000 and 130,000/mm3); an increase of the seroconversion enzyme of angiotensin (75 UI; N less than 52 UI); are normal or negative: ESR, protein electrophoresis, immunological tests. The diagnosis of AHE is held back and the clinical evolution is done in several stages: under general corticotherapy (prednisone 1 mg/kg/j): progressive decrease of the nodules, but stopping of the therapy by the patient after 4 months; testing of treatment by thalidomide (100 mg/day) interrupted after 2 weeks because of the aggravation of the thrombopenia (25,000/mm3); occurrence of a thrombopenic purpura (TP) (amount of platelets 10,000/mm3) without a serious haemorrhagic syndrome, evolving in a parallel way to the outbreak of AHE.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex Hormones↗

PubMedDate not supplied

Calcium antagonists reduce the extent of infarction in rat middle cerebral artery occlusion model as determined by quantitative magnetic resonance imaging.

The appearance and evolution of brain infarcts over 3 days following proximal occlusion of the left middle cerebral artery (MCA) in SHR rats were measured non-invasively by magnetic resonance imaging (MRI). Infarcts were clearly visible in coronal, T2 weighted brain sections, 24, 48 and 72 h after MCA occlusion in the left hemisphere, as areas of increased NMR signals. The infarcts were quantified by pixel counting in each section, the sum of 4 sections representing an accurate estimate of the total infarct size. The location and extent of infarction, determined by MRI, were found to be highly reproducible and correlated well with post-mortem histological and biochemical data. A neurological score, made every 24 h, paralleled the evolution of the infarct size, which culminated after 48 h. Pre- or post-treatment of MCA occluded rats with the dihydropyridine calcium antagonist PN 200-110 resulted in a substantial reduction of infarct size, determined by MRI 24, 48 and 72 h after infarction, compared to vehicle treated controls. These findings were corroborated by corresponding improvements of the neurological scores as well as histological and biochemical data. Post-treatment with nimodipine showed qualitatively similar effects. These results support the notion that calcium antagonists, through vascular and/or metabolic mechanisms, are effective in treating acute stroke. Since they were obtained in a chronic, relevant model of stroke with a method directly applicable also to humans, they should encourage further clinical studies with calcium antagonists.

Animals↗

PubMed2026

Tracking the shifting landscape of SARS-CoV-2 variants in Lebanon among healthcare workers and hospitalized patients.

UNLABELLED: Genomic surveillance of SARS-CoV-2 is critical for tracking viral evolution and informing public health responses. This study characterized variants circulating among healthcare workers (HCWs) and hospitalized patients in Lebanon between January 2022 and September 2024. A total of 530 SARS-CoV-2-positive nasopharyngeal swabs were collected from five Lebanese governorates and subjected to whole-genome sequencing. Correlations between variant circulation and a number of demographic and clinical variables were assessed. Most HCWs were female (64%), young adults (20-30 years, 39%), and had no comorbidities (97%). In contrast, hospitalized patients were mostly older adults (>60 years, 55.6%) with underlying conditions (77%). Early 2022 was marked by BA.1- and BA.2-like Omicron variants, followed by the predominance of BA.5-like lineages. In 2023, recombinant XBB sublineages became widespread. By 2024, these were largely replaced by next-generation variants, including JN.1 and KP.3.1.1. Despite differences in demographics and exposure risk, both groups showed parallel variant evolution. These findings reflect global and regional patterns and highlight the dynamic nature of SARS-CoV-2 circulation in Lebanon. IMPORTANCE: This study provides a comprehensive snapshot of SARS-CoV-2 variant evolution in Lebanon between 2022 and 2024, focusing on healthcare workers and hospitalized patients. By combining genomic and clinical data, it reveals how successive Omicron subvariants emerged and spread within key population groups. The detection of diverse and evolving lineages, including XBB recombinants and next-generation variants such as JN.1, underscores the ongoing antigenic drift of SARS-CoV-2. These insights reinforce the value of continued genomic surveillance for pandemic preparedness, especially in regions where data remain limited. Understanding local variant dynamics can guide targeted vaccination strategies and health policy decisions.

Humans↗

PubMed1997

Effect of hypothermia on microglial reaction in ischemic brain.

Intra-ischemic hypothermia is known to protect neurons against ischemic injury. Microglial cells have been shown to become activated following ischemia and are speculated to play significant roles in the evolution of ischemic neuronal injury. In this study, we examined the effect of intra-ischemic hypothermia on the microglial reaction in the hippocampus following transient forebrain ischemia produced in gerbils by 10 min bilateral carotid occlusion at 30 degrees C or at 37 degrees C, followed by normothermic reperfusion for 1-7 days. Microglial cells were visualized by histochemical staining with isolectin-B4 from Griffonia simplicifolia. Brains subjected to normothermic ischemia showed activation of microglia at 1 day post-ischemia; this increased with further recirculation, becoming intense by 3 days and diminished by 7 days. Ischemia under hypothermic conditions was not associated with activation of microglia, and these brains showed no significant neuronal damage, whereas the brains subjected to normothermic ischemia showed extensive neuronal necrosis in the CA1 region after 1 and 7 days reperfusion. The presence of activated microglial cells in the CA1 region prior to and in parallel with evolution of ischemic neuronal damage, the lack of such activation in brains subjected to the neuroprotective action of intra-ischemic hypothermia, together with the known potential capability of microglial cells to release cytotoxic substances appear to indicate that these cells could contribute significantly to ischemic neuronal necrosis.

Animals↗