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PubMed2002

National study of microphthalmia, anophthalmia, and coloboma (MAC) in Scotland: investigation of genetic aetiology.

We report an epidemiological and genetic study attempting complete ascertainment of subjects with microphthalmia, anophthalmia, and coloboma (MAC) born in Scotland during a 16 year period beginning on 1 January 1981. A total of 198 cases were confirmed giving a minimum live birth prevalence of 19 per 100 000. One hundred and twenty-two MAC cases (61.6%) from 115 different families were clinically examined and detailed pregnancy, medical, and family histories obtained. A simple, rational, and apparently robust classification of the eye phenotype was developed based on the presence or absence of a defect in closure of the optic (choroidal) fissure. A total of 85/122 (69.7%) of cases had optic fissure closure defects (OFCD), 12/122 (9.8%) had non-OFCD, and 25/122 (20.5%) had defects that were unclassifiable owing to the severity of the corneal or anterior chamber abnormality. Segregation analysis assuming single and multiple incomplete ascertainment, respectively, returned a sib recurrence risk of 6% and 10% in the whole group and 8.1% and 13.3% in the OFCD subgroup. Significant recurrence risks were found in both unilateral and bilateral disease. In four families, one parent had an OFCD, two of which were new diagnoses in asymptomatic subjects. All recurrences in first degree relatives occurred in the OFCD group with a single first cousin recurrence seen in the non-OFCD group. A total of 84/122 of the MAC cases were screened for mutations in the coding regions of PAX6, CHX10, and SIX3. No pathogenic mutations were identified in the OFCD cases. A single PAX6 homeodomain missense mutation was identified in a subject with partial aniridia that had been initially misclassified as coloboma.

Anophthalmos↗
PubMed2007

Separation of sequences from host-pathogen interface using triplet nucleotide frequencies.

The identification of genes involved in host-pathogen interactions is important for the elucidation of mechanisms of disease resistance and host susceptibility. A traditional way to classify the origin of genes sampled from a pool of mixed cDNA is through sequence similarity to known genes from either the pathogen or host organism or other closely related species. This approach does not work when the identified sequence has no close homologues in the sequence databases. In our previous studies, we classified genes using their codon frequencies. This method, however, explicitly required the prediction of CDS regions and thus could not be applied to sequences composed from the non-coding regions of genes. In this study, we show that the use of sliding-window triplet frequencies extends the application of the algorithm to both coding and non-coding sequences and also increases the prediction accuracy of a Support Vector Machine classifier from 95.6+/-0.3 to 96.5+/-0.2. Thus the use of the triplet frequencies increased the prediction accuracy of the new method by more than 20% compared to our previous approach. A functional analysis of sequences detected gene families having significantly higher or lower probability to be correctly classified compared to the average accuracy of the method is described. The server to perform classification of EST sequences using triplet frequencies is available at (URL: http://mips.gsf.de/proj/est3).

Algorithms↗
PubMed2005

Community-level physiological profiles of cloacal microbes in songbirds (order: Passeriformes): variation due to host species, host diet, and habitat.

The relationship between microorganisms and birds has received increased attention recently. The state of knowledge of this relationship, however, is based largely on examination of sick or dead birds, and knowledge of the prevalence and community structure and function of microbes in healthy wild populations is limited. Using carbon substrate utilization profiles, microbial communities were examined in 91 cloacal samples from 14 species within apparently healthy summer and winter passerine populations. Within each season, gradient lengths and eigenvalues from ordination analyses suggested that many samples differed in their carbon substrate utilization and several had very different communities. Cloacal microbe carbon utilization profiles were distinguishable among host species, season-specific diet, and study site in the ordination analyses. However, these patterns were only observed for the analysis of the summer data set. The results of this study support the idea that the avian host's microbial community, relative to carbon substrate utilization, is related to host diet. Previously, this pattern had only been reported for potential pathogens isolated from the avian cloaca. Study site-specific patterns in the ordination analysis suggest that environmental conditions at a particular study site may influence cloacal microbial communities in birds. Results of this study indicate that examination of community-level physiological profiles may be a useful technique for distinguishing among avian cloacal samples, similar to that already established for discriminating aqueous and soil samples. Future studies that correlate microbe physiological profiles to condition-based indices of avian hosts may be most useful for eventually using the profile as an indicator of environmental conditions experienced by hosts.

Animals↗
PubMed2002

Tiamulin activity against fastidious and nonfastidious veterinary and human bacterial isolates: initial development of in vitro susceptibility test methods.

Tiamulin is a pleuromutilin derivative used in veterinary practice for the control and specific therapy of infections in swine. This report summarizes studies to establish standardized susceptibility testing methods, interpretive criteria, and reagent details for use in veterinary methods recently developed by the National Committee for Clinical Laboratory Standards (NCCLS) (standards M31-A and M37-A, NCCLS, Wayne, Pa., 1999). A total of 636 fastidious and nonfastidious animal and human pathogens were processed by using media and procedures described by the NCCLS. Tiamulin disk diffusion tests used a 30-microg disk concentration, and the proposed MIC breakpoints corresponding to levels achievable in animal target tissues (lung) were < or =4 microg/ml for susceptibility and > or =32 microg/ml for resistance. Correlate zone diameters for specific nonfastidious species were as follows: for Pasteurella multocida and staphylococci tested on Mueller-Hinton agar, susceptibility at > or =19 mm and resistance at < or =11 mm, and for Actinobacillus suis, Erysipelothrix rhusiopathiae, and Streptococcus suis tested on enriched chocolate Mueller-Hinton agar, susceptibility at > or =16 mm and resistance at < or =8 mm. When Actinobacillus pleuropneumoniae was tested, a susceptibility breakpoint of < or =16 microg/ml (> or =9 mm) was suggested for veterinary fastidious medium broth and enriched chocolate Mueller-Hinton agar. Absolute categorical agreement between NCCLS dilution and disk diffusion test results with these criteria ranged from 90.5 to 96.2%. Tiamulin susceptibility testing methods appear to be accurate in their categorical classification for indicated species, and their availability will allow immediate testing of animal isolates to guide therapy via appropriate levels of dosing and to monitor the development of resistance for agents in this unique class.

Humans↗
PubMed2006

[Autoantibodies specifically detected in patients with polymyositis/dermatomyositis].

Polymyositis/Dermatomyositis (PM/DM) is a chronic inflammatory disorder that culminates in injury to the skin and muscle and, sometimes, is accompanied by interstitial lung disease (ILD). A number of autoantibodies are associated with myositis, including those specific for aminoacyl-tRNA synthetase (anti-ARS), signal recognition particle (anti-SRP), and Mi-2. These autoantibodies have proven to be useful in the diagnosis and classification of the diseases and are predictive of prognosis. It has been known that certain patients may have typical DM skin manifestations without clinical evidence of myositis for at least 2 years (Clinically Amyopathic DM; C-ADM). Although classical myositis-related antibodies are well known, specificities related to C-ADM have not been examined in detail. Therefore, we have examined sera from 15 Japanese patients with C-ADM to identify additional autoantibodies associated with this disease. Eight sera of C-ADM patient recognized a polypeptide of approximately 140 kDa and we named this new antibody specificity anti-CADM-140. Anti-CADM-140 antibodies were detected in 8 of 42 patients with DM, but not in patients with other connective tissue diseases or idiopathic pulmonary fibrosis. It is noteworthy that DM patients with anti-CADM-140 had significantly more rapidly progressive ILD when compared to patients without anti-CADM-140 (50% vs 6%, P=0.008). Further studies of the pathogenicity of these autoantibodies specificity may provide insight into the pathogenic mechanisms of PM/DM accompanied by rapidly progressive ILD.

Adult↗
PubMed2003

Immune restoration disease in HIV-infected individuals receiving highly active antiretroviral therapy: clinical and immunological characteristics.

BACKGROUND: HIV-infected patients responding to HAART can show a diverse spectrum of symptoms caused by inflammatory reaction. The pathogenesis of this phenomenon, called immune restoration disease (IRD), is unclear. This study describes the spectrum of IRD and analyses the immunological and clinical parameters that could be related to its development. METHODS: In a retrospective, matched case-control study, 17 HIV-infected individuals who developed inflammatory symptoms < 12 months after initiation of HAART were included. HIV-infected controls were matched for age, gender and CDC classification. Factors included in the analysis were: CD4+ and CD8+ cell counts, deltaCD4+ and deltaCD8+, CD4/CD8 ratios, HIV-1-RNA load (VL), AVL and the number of CDC events prior to HAART. RESULTS: The median time after initiation of HAART and developing IRD (n = 17) was 72 days (range 2-319). In nine cases (53%) a mycobacterial infection was identified as the underlying cause. HAART was started at a mean CD4+ count (+/- SD) of 55 x 10(6) /l (+/- 59) and 85 x 10(6) /l (+/- 78.0) for cases and controls, respectively (p = 0.13). After initiation of HAART, the CD4+ count showed a 10.6 fold increase at the onset of IRD in the cases and a 2.7 fold increase in the controls in an equal period of time (p = 0.020). The other parameters analysed did not differ significantly between cases and controls. CONCLUSION: We conclude that the risk of developing IRD is associated with a high-fold increase in CD4+ lymphocytes. In this study, mycobacteria are the pathogens most frequently associated with IRD.

AIDS-Related Opportunistic Infections↗
PubMed1994

Specific identification of Candida albicans by hybridization with oligonucleotides derived from ribosomal DNA internal spacers.

In order to develop DNA probes for rapid, sensitive and specific detection of the pathogenic yeast species Candida albicans, we carried out comparative sequence analysis of the two internal transcribed spacer regions (ITS1 and ITS2) of the ribosomal DNA (rDNA) units of C. albicans and the closely related pathogenic species C. tropicalis. While overall sequence similarity between the two species was considerable (65-75%), both ITS1 and ITS2 were found to contain distinct regions with sufficient sequence divergence to make them suitable as specific target sites for the identification of C. albicans. On the basis of these results one ITS1-derived (ANAB1) and two ITS2-derived (ANAB2 and ANAB3) oligonucleotides were selected, chemically synthesized, and used as hybridization probes. Their specificity and reliability were evaluated in dot-blot hybridization experiments with total genomic DNA from 13 strains of medically important Candida species, six strains of other yeast genera associated with man and animals, and ten strains previously identified as C. albicans by phenotypic criteria. Under well-defined hybridization conditions the three probes hybridized exclusively with DNA derived from strains belonging to the species C. albicans, thus demonstrating their potential clinical usefulness. The failure of four of the (presumed) C. albicans strains to show hybridization to the ITS probes sheds doubt upon their taxonomic classification, which is reinforced by other phenotypic aspects of these strains.

Base Sequence↗
PubMed2001

Genetic differences between humans and great apes.

The remarkable similarity among the genomes of humans and the African great apes could warrant their classification together as a single genus. However, whereas there are many similarities in the biology, life history, and behavior of humans and great apes, there are also many striking differences that need to be explained. The complete sequencing of the human genome creates an opportunity to ask which genes are involved in those differences. A logical approach would be to use the chimpanzee genome for comparison and the other great ape genomes for confirmation. Until such a great ape genome project can become reality, the next best approach must be educated guesses of where the genetic differences may lie and a careful analysis of differences that we do know about. Our group recently discovered a human-specific inactivating mutation in the CMP-sialic acid hydroxylase gene, which results in the loss of expression of a common mammalian cell-surface sugar throughout all cells in the human body. We are currently investigating the implications of this difference for a variety of issues relevant to humans, ranging from pathogen susceptibility to brain development. Evaluating the uniqueness of this finding has also led us to explore the existing literature on the broader issue of genetic differences between humans and great apes. The aim of this brief review is to consider a listing of currently known genetic differences between humans and great apes and to suggest avenues for future research. The differences reported between human and great ape genomes include cytogenetic differences, differences in the type and number of repetitive genomic DNA and transposable elements, abundance and distribution of endogenous retroviruses, the presence and extent of allelic polymorphisms, specific gene inactivation events, gene sequence differences, gene duplications, single nucleotide polymorphisms, gene expression differences, and messenger RNA splicing variations. Evaluation of the reported findings in all these categories indicates that the CMP-sialic hydroxylase mutation is the only one that has so far been shown to result in a global biochemical and structural difference between humans and great apes. Several of the other known genetic dissimilarities deserve more exploration at the functional level. Among the areas of focus for the future should be genes affecting development, mental maturation, reproductive biology, and other aspects of life history. The approaches taken should include both going from the genome up to the adaptive potential of the organisms and going from novel adaptive regimes down to the relevant repercussions in the genome. Also, as much as we desire a simple genetic explanation for the human phenomenon, it is much more probable that our evolution occurred in multiple genetic steps, many of which must have left detectable footprints in our genomes. Ultimately, we need to know the exact number of genetic steps, the order in which they occurred, and the temporal, spatial, environmental, and cultural contexts that determined their impact on human evolution.

Animals↗
PubMed1991

Evaluation of mortality in surgical neonates over a 10-year period: nonpreventable, permissible, and preventable death.

The mortality pattern and causes of death in surgical neonates were evaluated over the period of 1980 through 1990 in order to assess whether any deaths might have been prevented. In the study period 1,010 neonates were admitted, 104 of whom died (10%). These 104 neonates formed our study population. The Clinical Classification System (CCS) and the Therapeutic Intervention Scoring System (TISS) were used to assess the severity of illness. All 104 nonsurvivors were seriously ill (CCS 3 and 4; TISS greater than 20). The mortality pattern was classified in three groups. Group A (nonpreventable death) included 56 deaths, 48 of which were due to the underlying disease. The other 8 patients died of a nonpreventable complication of treatment. Eleven of the patients in group B (permissible death) had (multiple) congenital anomalies associated with chromosomal anomalies. Three of them were not treated and in the other 8 treatment was initially started but later withdrawn. In most of the other 14 patients further treatment was withdrawn because of serious postoperative complications or inoperable cardiac anomalies. Group C (preventable death) consisted of 23 patients. Six of 10 had irreversible brain damage due to prolonged hypoxemia. In the other 13 patients of group C, death was due to sepsis acquired in the postoperative period and treated inadequately. Staphylococcus epidermidis was the most frequent isolated pathogen (7/13).

Cause of Death↗
PubMed2002

Close genetic and phenotypic relatedness between mycoplasma ovine/caprine serogroup 11 and Mycoplasma bovigenitalium.

Strains of Mycoplasma ovine/caprine serogroup 11, isolated from infertile sheep, were compared to the type strain, 2D, and to strains of the cattle pathogen M. bovigenitalium, including the type strain, PG11. Examination of these strains by growth inhibition and immune fluorescence tests showed strong serological cross reactivity between M. serogroup 11 and M. bovigenitalium but not with other ruminant mycoplasmas. Substrate oxidation and growth studies did not show any consistent differences between M. serogroup 11 and M. bovigenitalium strains; all strains assigned to both groups were adapted to the utilisation of a small range of organic acids as energy sources. DNA:DNA hybridisation, carried out between DIG labelled reference strains of M. serogroup 11 and M. bovigenitalium and field isolates of these two mycoplasmas showed a particularly close relationship with hybridisation rates all greater than 70% and, mostly, closer to 90%. Sequencing of the 16S ribosomal RNA gene region of the M. serogroup 11 and M. bovigenitalium strains as well as the respective type strains revealed very high overall homologies of 99.5%. In summary, the results showed a very close phenotypic and genotypic relatedness between these two ruminant mycoplasmas which justifies their classification into a single species.

Animals↗
PubMed2006

The promise and the potential consequences of the global transport of mycorrhizal fungal inoculum.

Advances in ecology during the past decade have led to a much more detailed understanding of the potential negative consequences of species' introductions. Moreover, recent studies of mycorrhizal symbionts have led to an increased knowledge of the potential utility of fungal inoculations in agricultural, horticultural and ecological management. The intentional movement of mycorrhizal fungal species is growing, but the concomitant potential for negative ecological consequences of invasions by mycorrhizal fungi is poorly understood. We assess the degree to which introductions of mycorrhizal fungi may lead to unintended negative, and potentially costly, consequences. Our purpose is to make recommendations regarding appropriate management guidelines and highlight top priority research needs. Given the difficulty in discerning invasive species problems associated with mycorrhizal inoculations, we recommend the following. First, careful assessment documenting the need for inoculation, and the likelihood of success, should be conducted prior to inoculation because inoculations are not universally beneficial. Second, invasive species problems are costly and often impossible to control by the time they are recognized. We recommend using local inoculum sources whenever possible. Third, non-sterile cultures of inoculum can result in the movement of saprobes and pathogens as well as mutualists. We recommend using material that has been produced through sterile culture when local inoculum is not available. Finally, life-history characteristics of inoculated fungi may provide general guidelines relative to the likelihood of establishment and spread. We recommend that, when using non-local fungi, managers choose fungal taxa that carry life-history traits that may minimize the likelihood of deleterious invasive species problems. Additional research is needed on the potential of mycorrhizal fungi to spread to non-target areas and cause ecological damage.

Agriculture↗
PubMed1999

QTc dispersion and complex ventricular arrhythmias in untreated newly presenting hypertensive patients.

Increased dispersion of ventricular repolarisation (increased QT dispersion) is believed to predispose to arrhythmias associated with sudden death in certain cardiac diseases. Hypertension is also associated with increased risk of sudden death, particularly in those with left ventricular hypertrophy (LVH). Therefore, the first aim of this study is to look into the possible pathogenic role of QT dispersion on the ventricular arrhythmias occurring in a group of never-treated hypertensive patients. The second aim is to look at other possible determinants of QT dispersion (ie, level of blood pressure, hypokalaemia, electrocardiographic LVH and presence or absence of strain pattern) in hypertensive patients, and their relevance to complex ventricular arrhythmias. QTc (corrected QT) was measured in 70 newly presenting (never-treated) hypertensive patients (47 male, 23 female, mean age 51.9 +/- 12.5 years) from a standard 12-lead surface electrocardiogram (ECG). Blood pressure measurements and 24-h ECG holter recordings were performed in all patients. Serum potassium level was measured in 51 of the patients. Ventricular arrhythmias were classified using a modified Lown's scoring system. Maximum QTc, minimum QTc and QTc dispersion for all patients were 442 +/- 30.3 ms, 380 +/- 26.7 ms and 61.5 +/- 21.6 ms respectively. High grade ventricular arrhythmias (Lown's score >/=3) were found in 43% of the patients. The QTc dispersion was strongly correlated with the Lown's classification of arrhythmia and the age of the patients. Patients with more severe ectopy (Lown's score >/=3) were significantly older (57.4 +/- 10.3 years) compared to those with score </=2 (48.3 +/- 12.6 years) (P = 0.0067) and had a significantly greater QTc dispersion (69.9 +/- 22.5 ms vs55.2 +/- 18. 8 ms; P = 0.002). Presence of electrocardiographic strain did not affect the severity of arrhythmia, as 29% of the patients with LVH and strain had grade >/=3 Lown's score compared to 39% in the group with LVH but without strain. In the presence of relative hypokalaemia, hypertensive patients with LVH showed more QTc dispersion (85.7 +/- 15.5 ms) and a greater tendency for complex ventricular arrhythmias (100% grade >/=3 Lown's score) compared to those with LVH and normal serum potassium levels (64.1 +/- 22.6 ms and 35%, QTc dispersion and Lown's score >/=3, respectively P = 0. 05). The level of blood pressure had no effect on either the QTc dispersion or the prevalence of complex ventricular arrhythmias. Prevalence of complex ventricular arrhythmias in hypertensive patients is strongly correlated with QTc dispersion and age. When hypertensive patients with LVH have low potassium levels the risk of developing complex ventricular arrhythmias is significantly increased.

Aging↗
PubMed1984

Chronic myeloproliferative disorders (CMPD).

The wide clinical range of CMPD can be understood as leukaemia of pluripotent stem cells according to the pathogenic concepts reviewed above. Blastic metamorphoses of CMPD are regressions to a more primitive level of cellular differentiation. The predominant proliferative cell line characterizes the classical entities of PV, PT and CML, and their different prognoses. Pure erythrocytic and megakaryocytic proliferations are more compatible with sustained physiologic bone marrow functions than granulocytic proliferations. The combinations of granulocytic and megakaryocytic growth are especially prone to develop MF/OMS, in which participation of immune reactions, of granulocytic and of platelet factors is probable. An etiologic role for ineffective thrombocytopoiesis is supported by experimental as well as by histologic evidence. Myelofibrosis and osteomyelosclerosis may have similar causes, but develop independently. The prevalence of the female sex among thrombocythaemic patients was proven statistically also for the increase of giant type megakaryocytes in the form of clusters in the bone marrow, and for longer median survival of females in CMPD, especially when there is megakaryocytosis in the bone marrow. It is assumed that females may be better protected against the detrimentous effects of abnormal platelet production. An arbitrary classification according to haematologic and histologic criteria was applied to PV, PT and CML, and groups with typical and atypical haematologic and histologic signs were distinguished. The latter cannot be separated from each other by their various haematologic manifestations, but by histology and their different propensity to progress into more immature and/or fibrotic stages. Three major groups are characterized by histology: mixed granulocytic-megakaryocytic myelosis with giant megakaryocytic clusters, a similar variant with diffuse distribution of giant megakaryocytes, and immature and/or pleomorphic megakaryocytic myelosis. Transitions from each of these groups have been observed as well as transitions from each of the typical CMPD-entities into these less typical forms. CML, frequently accompanied by dwarf-megakaryocytes, often develops into pleomorphic megakaryocytic or blastic myelosis. Blastic dedifferentiation and myelofibrosis manifest themselves as closely related end stages, to which principally all groups proceed after a longer or shorter period of time, modified by the proliferating cell lines in each group. Clinical, experimental and histologic evidence of this natural history has been reviewed, with special emphasis on the re-evaluation of technically optimal bone marrow biopsies of untreated patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1993

Molecular biology and evolution of filoviruses.

The family Filoviridae contains extremely pathogenic human viruses causing a fulminating, febrile hemorrhagic disease. Filoviruses are enveloped, filamentous particles with a nonsegmented negative-strand RNA genome showing the gene arrangement 3'-NP-VP35-VP40-GP-VP30-VP24-L-5'. Genes are flanked by highly conserved transcriptional signals and are generally separated by variable intergenic regions. They are transcribed into monocistronic polyadenylated messenger RNAs which contain relatively long 5' and 3' untranslated regions. Seven structural proteins are encoded by the genome of which four form the helical nucleocapsid (NP-VP35-VP30-L), two are membrane-associated (VP40-VP24), and one is a transmembrane glycoprotein (GP). Comparison of filovirus genomes with those of other nonsegmented negative-strand RNA viruses suggest comparable mechanisms of transcription and replication and a common evolutionary lineage for all these viruses. Sequence analyses of single genes, however, showed that filoviruses are more closely related to paramyxoviruses, particularly human respiratory syncytial virus. These data support the concept of the taxonomic order Mononegavirales for all nonsegmented negative-strand RNA viruses and the classification of Marburg virus, Ebola virus, and Reston virus in the family Filoviridae, separate from the families Paramyxoviridae and Rhabdoviridae.

Animals↗
PubMed2006

Fourier transform infrared (FT-IR) spectroscopy in bacteriology: towards a reference method for bacteria discrimination.

Rapid and reliable discrimination among clinically relevant pathogenic organisms is a crucial task in microbiology. Microorganism resistance to antimicrobial agents increases prevalence of infections. The possibility of Fourier transform infrared (FT-IR) spectroscopy to assess the overall molecular composition of microbial cells in a non-destructive manner is reflected in the specific spectral fingerprints highly typical for different microorganisms. With the objective of using FT-IR spectroscopy for discrimination between diverse microbial species and strains on a routine basis, a wide range of chemometrics techniques need to be applied. Still a major issue in using FT-IR for successful bacteria characterization is the method for spectra pre-processing. We analyzed different spectra pre-processing methods and their impact on the reduction of spectral variability and on the increase of robustness of chemometrics models. Different types of the Enterococcus faecium bacterial strain were classified according to chromosomal DNA restriction patterns produced by pulsed-field gel electrophoresis (PFGE). Samples were collected from human patients. Collected FT-IR spectra were used to verify if the same classification was obtained. In order to further optimize bacteria classification we investigated whether a selected combination of the most discriminative spectral regions could improve results. Two different variable selection methods (genetic algorithms (GAs) and bootstrapping) were investigated and their relative merit for bacteria classification is reported by comparing with results obtained using the entire spectra. Discriminant partial least-squares (Di-PLS) models based on corrected spectra showed improved predictive ability up to 40% when compared to equivalent models using the entire spectral range. The uncertainty in estimating scores was reduced by about 50% when compared to models with all wavelengths. Spectral ranges with relevant chemical information for Enterococcus faecium bacteria discrimination were outlined.

Bacterial Typing Techniques↗
PubMed1997

Xenorhabdus and Photorhabdus spp.: bugs that kill bugs.

Xenorhabdus and Photorhabdus spp. are gram negative gamma proteobacteria that form entomopathogenic symbioses with soil nematodes. They undergo a complex life cycle that involves a symbiotic stage, in which the bacteria are carried in the gut of the nematodes, and a pathogenic stage, in which susceptible insect prey are killed by the combined action of the nematode and the bacteria. Both bacteria produce antibiotics, intracellular protein crystals, and numerous other products. These traits change in phase variants, which arise when the bacteria are maintained under stationary phase conditions in the laboratory. Molecular biological studies suggest that Xenorhabdus and Photorhabdus spp. may serve as valuable model systems for studying signal transduction and transcriptional and posttranscriptional regulation of gene expression. Such studies also indicate that these bacterial groups, which had been previously considered to be very similar, may actually be quite different at the molecular level.

Animals↗
PubMed1979

[Primary pyelonephritis (the focal problem)].

On different experimental models of pyelonephritis in dogs and rabbits an experiment for the classification of the pathogenesis of this disease with the special questioning of the possible development of the so-called primary pyelonephritis was performed. A series of experiments consisted of 3 groups: 1. Injection of an E.-coli-suspension into the musculature of the urinary bladder of dogs and rabbits. 2. Injection of an E.-coli-suspension into the testicles of rabbits. 3. Injection of an E.-coli-suspension into the seminal bladders of rats. The experiments lasted 2 to 15 days and 16 to 110 days, respectively. In the second series of experiment in rats and rabbits an E.-coli-suspension was injected into the gall-bladder of rats and rabbits. Bacteriologic blood cultures and histologic investigations of the kidneys, the ureters, the wall of the urinary bladder and the adjacent lymphatic and fatty tissue as well as of the gall-bladders were performed. The results showed that the pyelonephritis developed secondarily after the infection of the other infected organs by haematogenic or interstitial dissemination of the pathogenic agents. Conclusions are drawn: 1. Every pyelonephritis, also the haematogenic, is a secondary process. 2. Therefore all must be done to find out the primary inflammatory change in the organism and to cure it. 3. Severe forms of the pyelonephritis may, on the other hand, effect as focus and evoke in inflammation of other organs on lymphogenic and haematogenic way. 4. Taking into consideration the facts mentioned perhaps the great number of pyelonephritiides having become latent might be reduced.

Animals↗
PubMed2025

Type and position of repeat interruptions as determinants of disease severity and expansion size in Friedreich ataxia.

PURPOSE: In Friedreich ataxia (FRDA) the size of the smaller GAA expansion is a major determinant of disease severity; interruption motifs were identified after the discovery of the pathogenic expansions; however, their impact is only recently investigated. METHODS: 164 patients with FRDA with biallelic expansions and 15 patients without FRDA were analyzed for interruption(s) number, position, and motif. Expansion size and age at onset of ataxia (AAO) were determined for patients with FRDA. RESULTS: Three groups of patients with FRDA were identified by the simultaneous analysis of the precise distance ("depth") between the interruptions (mostly nontriplet) and the 3' end of the expansion (P < .001), the smaller expansion size (P < .001), and AAO (P < .001). Classical FRDA corresponds to absence of interruption or interruption depth < 8 repeats, with AAO often <15 years (area under the curve [AUC] = 0.90; 95% CI, 0.84-0.96); LOFA to interruption depth of 8 to 18 repeats (AUC = 0.97; 95% CI, 0.94-1), with AAO 15 to 34 years (AUC = 1; 95% CI, 1-1); and vLOFA to interruption depth > 18 (AUC = 0.97; 95% CI, 0.92-1), with AAO > 34 years. Multiple (>5) triplet interruptions hamper further expansion. CONCLUSION: This study provides the molecular basis for a novel classification of FRDA that should be recommended for correct diagnosis.

Humans↗