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PubMedDate not supplied

1H magnetic resonance spectroscopy evidence that aberrant crypt foci are preneoplastic lesions in the colon.

BACKGROUND: Histopathological and genetic studies support the hypothesis that aberrant crypt foci (ACF) represent one of the earliest events in colon carcinogenesis. The purpose of this study is to make use of 1H MRS in conjunction with multivariate methods of analysis to ascertain the validity of the above mentioned hypothesis. MATERIALS AND METHODS: ACF, colonic mucosa and tumor samples taken from thirty-two carcinogen (azoxymethane)-treated Sprague Dawley rats, and of colon mucosa taken from ten healthy animals, were investigated ex vivo by 1H MRS and analyzed using multivariate methods of analysis. RESULTS: The 1H magnetic resonance peak intensities and areas of ACF lie between those from normal and carcinogen- treated mucosa samples and tumors. Multivariate analysis classification of the spectra suggests that the ACF exhibit biochemical characteristics intermediate between the control and AOM-mucosa samples and the tumor groups. CONCLUSION: The use of sophisticated methods of data classification has enabled us to support the hypothesis that ACF represent preneoplastic lesions of the colon.

Animals↗
PubMed1998

Pneumocystis carinii: a fungus resistant to antifungal therapies - mechanisms of action of antipneumocystis drugs.

Pneumocystis carinii is a pathogen that causes a potentially lethal pneumonia in patients with AIDS and other immunodeficiency states. This review discusses the mechanisms of action of four classes of antipneumocystis agents: inhibitors of ergosterol synthesis and function, 1,3-beta-glucan synthase inhibitors, antifolates and DNA binding agents. Investigations of P. carinii's biologic pathways affected by the antipneumocystis actions of each of these classes of agents has generated important insights into the organism's basic biology and supports the organism's classification as a fungus. In addition, this review discusses some recent P. carinii research and its potential impact on drug development.

Journal Article↗
PubMed2003

New developments in anti-tumor efficacy and malignant transformation of human natural killer cells.

For decades, the driving force behind many immunologic studies has been the hope of augmenting anti-cancer therapy through targeted immune-based strategies. The question remains: can immune cells be successfully manipulated to augment chemotherapy and aid in the elimination of malignancy? Such efforts have included work with natural killer (NK) cells, large granular lymphocytes that contribute to the early innate immune response by nonspecifically killing pathogens, virus-infected cells, and tumor cells, and by producing important early immunoregulatory cytokines such as interferon gamma (IFN-gamma). These qualities have made NK cells attractive candidates for therapy aimed at boosting host immunity against tumor cells and infectious pathogens. Recent advances in our understanding of how NK cells select targets for killing have improved our ability to design and test more effective immune-targeted therapies. However, our understanding of NK leukemias and lymphomas remains incomplete. NK leukemias and lymphomas, while rare, represent a significant challenge to the patients and physicians coping with them, as most lack effective treatment strategies. This brief review will summarize current directions in NK cell immune therapy and give an update on the classification and treatment of NK malignancies.

Cell Transformation, Neoplastic↗
PubMed2001

Proposal to transfer some members of the genera Haemobartonella and Eperythrozoon to the genus Mycoplasma with descriptions of 'Candidatus Mycoplasma haemofelis', 'Candidatus Mycoplasma haemomuris', 'Candidatus Mycoplasma haemosuis' and 'Candidatus Mycoplasma wenyonii'.

Cell-wall-less uncultivated parasitic bacteria that attach to the surface of host erythrocytes currently are classified in the order Rickettsiales, family Anaplasmataceae, in the genera Haemobartonella and Eperythrozoon. Recently 16S rRNA gene sequences have been determined for four of these species: Haemobartonella felis and Haemobartonella muris and Eperythrozoon suis and Eperythrozoon wenyonii. Phylogenetic analysis of these sequence data shows that these haemotrophic bacteria are closely related to species in the genus Mycoplasma (class Mollicutes). These haemotrophic bacteria form a new phylogenetic cluster within the so-called pneumoniae group of Mycoplasma and share properties with one another as well as with other members of the pneumoniae group. These studies clearly indicate that the classification of these taxa should be changed to reflect their phylogenetic affiliation and the following is proposed: (i) that Haemobartonella felis and Haemobartonella muris should be transferred to the genus Mycoplasma as 'Candidatus Mycoplasma haemofelis' and 'Candidatus Mycoplasma haemomuris' and (ii) that Eperythrozoon suis and Eperythrozoon wenyonii should be transferred to the genus Mycoplasma as 'Candidatus Mycoplasma haemosuis' and 'Candidatus Mycoplasma wenyonii'. The former Haemobartonella and Eperythrozoon species described here represent a new group of parasitic mycoplasmas that possess a pathogenic capacity previously unrecognized among the mollicutes. These haemotrophic mycoplasmas have been given the trivial name haemoplasmas. These results call into question the affiliation of the remaining officially named species of Haemobartonella and Eperythrozoon which should be considered species of uncertain affiliation pending the resolution of their phylogenetic status.

Anaplasmataceae↗
PubMed1995

[Cranio-cerebral dermoid and epidermoid cysts. Classification and pathogenesis].

The pathogenesis of cranial dermoids and epidermoids is still controversial, owing to the multiple etiologies and locations of these lesions. We reviewed 25 cases, classified as follows: extradural lesion of the calvarium; of the occipital squama; dysraphic occipital lesions; and strictly intradural lesions. In the latter group, all lesions but one were in a paramedian, prenevraxial situation, and could be classified according to their situation relative to the tentorium cerebelli. In our series, strictly intradural dermoids are more often in a rostral situation, and epidermoids in a more caudal situation. Dermoids appear earlier in life than epidermoids, suggesting a more rapid growth due to eccrine secretion. For each group of lesions, the pathogenic hypotheses are studied. Inclusion of epidermal nests at different levels might result from traumatism, dysraphism, or developmental trouble in the lamination of the different layers of the meninges. Most intradural lesions trent to be related to the formation of Rathke's pouch and closure of the anterior neuropore.

Adult↗
PubMed1997

HIV-1 subtypes: implications for epidemiology, pathogenicity, vaccines and diagnostics. Workshop Report from the European Commission (DG XII, INCO-DC) and the Joint United Nations Programme on HIV/AIDS.

Forty-three AIDS scientists from Europe, Africa, the United States, Canada, India and China met in Dar es Salaam, Tanzania to discuss the implications of the global variation of HIV (list of participants included in Appendix). This meeting followed an earlier meeting of the Joint United Nations Programme on HIV/AIDS, held in 1996 in Berlin, Germany [1], in which HIV genetic variability was considered in relation to transmissibility. During the Tanzania meeting, available data pertaining to the biological consequences of HIV genetic variation and its ramifications with regard to epidemiology, diagnostics, classification, and vaccine design were systematically reviewed. There was consensus that classification based on genetically defined subtypes provides an important framework for making advances on understanding viral biology and immunology, and for vaccine development. In addition, other groupings of viruses based on immunological and biological characteristics would be also valuable and help to further refine our understanding of the implications of variability. Key elements of the discussion are summarized here in the context of a review of the current literature.

AIDS Vaccines↗
PubMed1998

Plasmid (1952-1997).

The term "plasmid" was introduced 45 years ago (J. Lederberg, 1952, Physiol. Rev. 32, 403-430) as a generic term for any extrachromosomal genetic particle. It was intended to clarify the classification of agents that had been thought of disjunctively as parasites, symbionts, organelles, or genes. For a decade or more it was confused with "episome," although that was carefully crafted (F. Jacob and E. L. Wollman, 1958, C. R. Acad. Sci. 247, 154-156) to mean agents with traffic in and out of chromosomes. Starting about 1970, plasmids became important reagents in molecular genetic research and biotechnology. They also play a cardinal role in the evolution of microbial resistance and of pathogenicity. The usage of the term has then escalated to its current peak of about 3000 published articles per year. The bedrock of genetic mechanism is no longer mitosis and meiosis of chromosomes; it is template-directed DNA assembly. This is often more readily studied and managed with the use of plasmids, which replicate autonomously outside the chromosomes. Some plasmids are also episomes, namely, they interact with the chromosomal genome, and other mobile elements may be transposed from one chromosomal locus to another without replicating autonomously.

Animals↗
PubMed2004

Purification of antilisterial bacteriocins.

In recent years, numerous contamination outbreaks, involving various pathogens (i.e., Listeria and Salmonella), have increased concern over food preservation. Research efforts have focused on the discovery of new molecules targeting such foodborne pathogens and therefore able to inhibit and or kill them. Lactic acid bacteria (LAB) extensively used in fermented foods for thousands of years not only improve their flavor and texture but also inhibit pathogenic and spoilage microorganisms. LAB inhibitory activity is primarily owing to pH decrease and competition for substrates. Antagonistic activity of LAB also depends on secreted antimicrobial compounds with a poor selectivity, such as metabolic compounds (i.e., hydrogen peroxide, acetoin, and others) or more specific ones like bacteriocins. The latter are proteinaceous compounds, ribosomally synthesized and subsequently secreted by Gram-positive as well as Gram-negative bacteria. Their antimicrobial activity is generally restricted to strains phylogenetically related to the producers.A classification of bacteriocins produced by LAB was first proposed by Klaenhammer in 1993 and was modified by Nes et al. in 1996; class I and class II bacteriocins are the most abundant and thoroughly studied. Bacteriocins from both classes exhibit antilisterial activity. Class I bacteriocins, namely, lantibiotics, have been widely studied, and among them, nisin is used in many countries as a preservative in food products. These bacteriocins are characterized by the presence, in their primary structure, of post-translationally modified amino acid residues (i.e., lanthionine and methylanthionine) that are formed. Class II bacteriocins, containing three subclasses, consist of small peptides that do not bear any modified amino acid residue. The most studied subclass corresponds to class IIa, also termed anti-Listeria bacteriocins. These peptides share strong structural homologies in their N-terminal domain, with the presence of one disulfide bond and a net positive charge. Their C-terminal domain is more variable but appears quite hydrophobic. Moreover, some of these bacteriocins, namely, sakacin G, pediocin PA-1, enterocin A, coagulin, and divercin V41, are characterized by the presence of a second disulfide bond in the C-terminal region.

Amino Acid Sequence↗
PubMedDate not supplied

Relationship between the immunosuppressive potential and the pathotype of Marek's disease virus isolates.

Isolates of Marek's disease virus (MDV) representing three pathotypes of differing virulence were compared for relative immunosuppressive properties in genetically susceptible P2a-strain and genetically resistant N2a-strain chickens. Criteria of immunosuppression were 1) persistence of early cytolytic infection (i.e., a delay or failure to enter latency) in lymphoid organs, 2) atrophy of the bursa of Fabricius and thymus as measured by organ weight proportional to body weight at 8 and 14 days postinfection (DPI), and 3) histopathologic evidence of necrosis and atrophy in lymphoid organs. No significant differences in infection level were observed among the pathotypes during the early (4-5 DPI) period of infection. However, the extent of persistent cytolytic infection at 7-8 DPI, based on numbers of tissues positive and mean scores in immunofluorescence tests, was greater (P < 0.05) for three isolates (RK1, 584A, 648A) in the highest virulence pathotype (very virulent-plus MDV [vv + MDV]) than for two isolates (JM16, GA5) in a lower virulence (virulent MDV [vMDV]) pathotype. Results from two isolates (RB1B, Md5) classified in the intermediate very virulent pathotype (very virulent MDV [vvMDV]) fell between those from the other two pathotypes. Similarly, there was a stepwise effect of viral pathotype in which the vv + MDV isolates caused the most severe damage to lymphoid organs in terms of atrophy (relative organ weights) and histopathologic changes. Organs from chickens infected with vv + MDVs showed little recovery between 8 and 14 DPI. The vMDV isolates caused the least severe damage, and lymphoid organs showed a significant return toward normal by 14 DPI; vvMDV isolates induced intermediate degrees of atrophy and recovery. The same pattern of relationship between virulence pathotype and degree of bursal and thymic atrophy was also observed in genetically resistant N2a chickens. These results suggest that the degree of immunosuppression is linked to virulence and that a simple measure of atrophic changes (relative organ weights) in the bursa of Fabricius and thymus might be useful in determining the pathotype classification of new MDV isolates. The basis for differences in immunosuppressive potential of MDV isolates needs further clarification.

Animals↗
PubMed2003

Genomic distribution and characterization of EST-derived resistance gene analogs (RGAs) in sugarcane.

A large sugarcane EST (expressed sequence tag) project recently gave us access to 261,609 EST sequences from sugarcane, assembled into 81,223 clusters. Among these, we identified 88 resistance gene analogs (RGAs) based on their homology to typical pathogen resistance genes, using a stringent BLAST search with a threshold e-value of e(-50). They included representatives of the three major groups of resistance genes with NBS/LRR, LRR or S/T KINASE domains. Fifty RGAs showed a total of 148 single-dose polymorphic RFLP markers, which could be located on the sugarcane reference genetic map (constructed in cultivar R570, 2n=approximately 115). Fifty-five SSR loci corresponding to 134 markers in R570 were also mapped to enable the classification of the various haplotypes into homology groups. Several RGA clusters were found. One cluster of two LRR-like loci mapped close to the only disease resistance gene known so far in sugarcane, which confers resistance to common rust. Detailed sequence comparison between two NBS/LRR RGA clusters in relation to their orthologs in rice and maize suggests their polyphyletic origins, and indicates that the degree of divergence between paralogous RGAs in sugarcane can be larger than that from an ortholog in a distant species.

Amino Acid Sequence↗
PubMed1997

Differentiation of Leptospira species and serovars by PCR-restriction endonuclease analysis, arbitrarily primed PCR and low-stringency PCR.

Reference strains from 30 serovars representing seven species of Leptospira and 48 recent isolates from human patients, dogs and rats, were characterised by polymerase chain reaction-restriction endonuclease analysis (PCR-REA), arbitrarily primed PCR (AP-PCR) and low stringency PCR (LS-PCR). PCR-REA analysis yielded seven groups among 29 serovars of pathogenic Leptospira; the non-pathogenic L. biflexa serovar patoc was not amplified with the primer pairs studied. AP-PCR and LS-PCR fingerprinting resulted in 25 and 21 distinct profiles, respectively, among the 30 reference strains. The results of the three PCR-based techniques were highly concordant and were in general agreement with those from previous DNA studies, confirming the high level of polymorphism among Leptospira species and serovars, and supported the concept of the serovar as the basic taxonomic unit of leptospiral classification. Results of the PCR-based typing methods for 11 randomised leptospiral strains, 36 clinical isolates from human patients and dogs and 12 survey isolates from trapped rats agreed with those from serological identification. With one exception, isolates of the same serovar gave identical profiles irrespective of the source. AP-PCR and LS-PCR are simple to perform and interpret, and appear to be useful for characterising isolates of Leptospira spp. for diagnostic and epidemiological purposes.

Animals↗
PubMed1996

[Motor neuron diseases. Present].

Recent progress in our understanding of motor neuron diseases, particularly those of degenerative pathogenesis such as spinal muscular atrophies (SMA) and amyotrophic lateral sclerosis (ALS), have to be described as historic. They are essentially of three types: 1) In first place are advances afforded by molecular genetics both in SMA (with the discovery of survival motor neurons and neuronal apoptosis inhibitor protein, which are markers of the disease and their pathogenetic mechanism) and in ALS (with the discovery of the super oxide dismutase [SOD1] gene, involved in the genesis of familial forms of ALS and other types of SMA such as certain forms of familial juvenile ALS, bulbar-spinal atrophy with gynecomasty and others). 2) In second place are biological data detailing the mechanisms of neuron death, whether programed or not, and emphasizing the importance of the so-called trophic or neurotrophin factors-whether nerve growth factor, brain-derived-neurotrophic factor, neurotrophin-3 or others whose effect of preventing neuron death has been demonstrated in vitro-as well as that of other substances such as Ca(2+)-activated neutral protease, which stabilizes synapses during development. It is assumed that one or another of these data will lead to therapeutic strategies for blocking the cascade of events that lead to neuron degeneration. 3) Finally, the strong impact of neuroimmunology in the field of neuromuscular pathology has been of interest mainly in neurogenic diseases marked purely and essentially be motor expression. As markers and pathogens, antiganglioside antibodies must necessarily be determined at this time in such entities as multifocal motor neuropathy, Guillain-Barré syndrome, acute axon motor neuropathy, Miller-Fisher syndrome and others, as their presence can inform therapeutic approaches. These three aspects and others currently under discussion will be treated in this course. At the same time the basic diagnostic aspects of motor neuron diseases will be emphasized: electrophysiologic assessment, on the one hand, and clinical features on the other. Establishing an exhaustive classification of SMA, from the earliest forms of infancy to adult types, is of great priority, as is exposing the full range of SMA according to whether distal or proximal predominance of atrophy is present. Our current understanding of the field is summarized in ten chapters on degenerative motor neuron diseases.

Amyotrophic Lateral Sclerosis↗
PubMed1997

[Benign laryngotracheal stenoses in pediatric age].

The diagnosis and treatment of infants and children with laryngo-tracheal pathology has changed substantially over the last 20 years. The change is the result of the continued evolution of diagnostic instruments, surgical techniques and new advancements in critical care medicine. Abnormalities in the development of the larynx may lead to congenital subglottic stenosis. A variety of pathogenic processes, either inflammatory or iatrogenic, also may damage the cricoid cartilage and lead to subglottic stenosis. The stenosis may involve alone or in combination the subglottis, glottis, upper cervical trachea. In this article the author reports a 12 years experience in 114 patients affected by benign laryngo-tracheal stenosis. These patients are classified in two groups: 1) 75 patients with congenital stenosis, 2) 39 patients with acquired stenosis. For the diagnose video-endoscopy has been used, and for the classification the Cotton's technique has been used. To get the best results in this pathology it is very important to have a multidisciplinary approach.

Child↗
PubMed2025

Extracting and calibrating evidence of variant pathogenicity from population biobank data.

Genomic medicine requires a robust evidence base of variant phenotypic impacts, which remains incomplete even in extensively studied genes with monogenic disease associations. Here, we evaluated the broad potential of using population cohort data to identify evidence that can be used in variant assessment. Across 41 genes related to 18 clinically actionable monogenic phenotypes, we calculated variant-level odds ratios of disease enrichment using data from 469,803 UK Biobank participants. We found significant differences in odds ratio values between ClinVar-labeled pathogenic and benign variants in 11 phenotypes, spanning both common and rare disorders. To facilitate clinical translation, we calibrated the strength of evidence provided by variant-level odds ratios to align with American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) interpretation guidelines (PS4 criterion) and found that odds ratios may reach "moderate," "strong," or "very strong" evidence, varying by phenotype and gene. Overall, we found that 2.6% (N = 12,350) of participants harbor a rare variant of uncertain significance (VUS) with at least moderate evidence of pathogenicity-an indication of potentially unrecognized disease risk. Finally, by incorporating computational and functional data alongside population-based odds ratios, we identified variants that met the criteria for clinical reclassification. Notably, using this approach, we identified that 12.4% of rare VUSs in LDLR seen in participants meet diagnostic criteria to be classified as likely pathogenic, demonstrating its potential to scale the reclassification of VUSs.

Humans↗
PubMed2000

Experimental evidence of host specificity of Bartonella infection in rodents.

A large number of Bartonella species and genetic variants were compared for their ability to cause bacteremia in different rodent species: the cotton rat (Sigmodon hispidus), white-footed mouse (Peromyscus leucopus), BALB/c mouse and Wistar rat. Experimental data supported field observations that host specificity can occur among certain Bartonella species and rodent species. Bacteremia could only be readily produced in cotton rats or white-footed mice if the strains used for inoculation were originally obtained from the same species or from a phylogenetically close species. A few Bartonella colonies could be observed in the blood of some BALB/c mice by 7 days after inoculation, but no evidence of the persistence of the infection was found. Host specificity suggests the possibility of a long co-speciation of Bartonella species with their rodent hosts. Host-parasite relationships measured by the duration and level of bacteremia and the minimal infectious dose may serve as additional criteria for classification of Bartonella isolates obtained from natural environments.

Animals↗
PubMed1995

Cerebral edema and intracranial pressure monitoring.

With the wide acceptance of liver transplantation as a therapeutic alternative in fulminant hepatic failure (FHF), the successful management of patients with this syndrome has acquired a new urgency. Topping the list of medical problems is the development of brain swelling. Two decades after the recognition of its importance, brain edema and intracranial hypertension still constitute a major cause of death in these patients. In a more recent classification of FHF, brain edema was especially prominent in those subjects with "hyperacute failure," in whom a period of 7 days or less elapsed between the development of jaundice and encephalopathy. The goal of this review is to discuss two aspects of this clinical problem. On one hand, elucidation of its pathogenesis should lead to a more rational therapeutic approach; such an information would also be valuable to understand the relationship between hepatic encephalopathy and brain edema, a source of controversy. Studies of pathogenic mechanisms are difficult to perform in humans and animal models of FHF have proven valuable, as brain swelling can be detected with some regularity. On the other hand, an increasing array of techniques is now available in the intensive care setting to monitor patients with FHF. Of these, intracranial pressure monitoring has received the most critical attention. However, concerns with the risks of craniotomy and the need to acquire more dynamic information has led several groups to explore non-invasive methods that evaluate the consequences of intracranial hypertension. Their role, though potentially exciting, is still uncertain.

Brain Edema↗
PubMed2026

Presence of globally prominent multidrug-resistant genotypes of Salmonella enterica serovar Typhi in New York State, 2016-2023.

The human-restricted enteric pathogen Salmonella enterica serovar Typhi (S. Typhi) is the causative agent of the life-threatening typhoid fever. Although S. Typhi incidence is relatively low in the USA, routine surveillance of S. Typhi is critical to track the emergence and spread of high-risk lineages in non-endemic areas. In this study, we analysed 151 genomes of S. Typhi isolates from patients who were clinically confirmed with typhoid fever across New York State between 2016 and 2023. We used the GenoTyphi classification scheme and identified established multidrug-resistant and extensively drug-resistant lineages. We detected the presence of the globally widespread genotype 4.3.1 (haplotype 58) and its derivative 4.3.1.1.P1, which recently emerged in Pakistan, as well as the Bangladesh-restricted lineages 3.3.2.Bd1 and 3.3.2.Bd2 in our dataset. Ten mutations and 14 acquired genes associated with antimicrobial resistance (AMR) were present across the entire population, with 86.8% of the genomes possessing at least one of these AMR determinants. The gyrA S83F mutation conferring quinolone and triclosan resistance was the most frequently detected (94 genomes). Combinations of dfrA7+catA1 (resistance to trimethoprim and chloramphenicol, respectively) and sul2+aph(3&#x2033;)-Ib+aph(6)-Id (resistance to sulphonamide and aminoglycosides, respectively) co-occurred frequently and were associated with IncQ and IncY plasmid replicons. Phylogenetic contextualization against a global dataset of 1,643 genomes from 20 countries across five continents, including other parts of the USA, from the same time period showed geographic intermingling, suggesting the spread of high-risk genotypes of international origins to New York State. Altogether, these findings reveal the presence of globally dominant resistant genotypes that are likely facilitated by human travel in New York State, where typhoid fever is not endemic. Long-term genomic surveillance is critical to AMR profiling, identifying genotypic shifts in regional S. Typhi populations, monitoring transmission routes and guiding effective public health interventions.

Salmonella typhi↗
PubMed2002

[Middle ear cholesteatoma: present-day concepts of etiology and pathogenesis].

Since J. Cruveilhier described cholesteatoma as the "pearly" tumor of the middle ear in 1828, the pathogenesis of cholesteatoma remained controversial. It is accepted that cholesteatoma may be congenital or acquired. Several pathogenic mechanisms have been proposed to explain the pathogenesis of congenital cholesteatoma. Proposed theories include ectopic epidermis rest, ingrowth of meatal epidermis, metaplasia and reflux of amniotic fluid. Four basic theories present the pathogenesis of acquired cholesteatoma: invagination of the tympanic membrane (retraction pocket cholesteatoma), basal cell proliferation, epithelial in-growth through a perforation (the immigration theory) and squamous metaplasia of middle ear epithelium. The aim of the article is to review the recent literature dealing with problems of the etiopathogenesis and classification of cholesteatoma.

Adult↗