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Effect of microsomal enzyme inducers and inhibitors on the toxicity of tunicamycin and corynetoxin, the causal agent of annual ryegrass toxicity.

Of the microsomal enzyme inducers and inhibitors tested in rats, the only one to modify the toxicity of tunicamycin or the closely-related corynetoxin, the causal agent of annual ryegrass toxicity, was phenobarbitone. It increased the LD50 of tunicamycin from 0.31 mg/kg to 0.77 mg/kg. Similar results were obtained with the related corynetoxin. Tunicamycin was also shown to be an inhibitor of cytochromes P-450. Rats sacrificed 48 h after receiving an LD50 dose of tunicamycin had cytochromes P-450 levels 30% that of controls. Rats pretreated with trans-stilbene oxide, which like phenobarbitone is an inducer of glutathione transferase, showed no decreased susceptibility to tunicamycin. These results suggest that neither hepatic cytochromes P-450 enzymes nor glutathione transferase is involved in detoxication of tunicamycin or corynetoxin in rats. The beneficial effect of phenobarbitone may be the result of a special kind of phenobarbitone-inducible enzyme which may not be P-450 dependent.

Animals↗

Could Borrelia burgdorferi be a causal agent of sarcoidosis?

Sarcoidosis is a multisystem granulomatous disorder of unknown etiology, most commonly affecting young adults presenting most frequently with bilateral hilar lymphadenopathy, pulmonary infiltrations, skin or eye lesions (1). Borrelia burgdorferi, the causal agent of Lyme disease, could also be responsible for sarcoidosis. Domestic animals may play a major role in transmitting the disease to humans. The modes of transmission to such animals and possible contact transmission to humans are still obscure and should be more fully investigated. Small rodents have been found to play a role as reservoirs for Borrelia burgdorferi. They are suspected to constitute an important source of contamination for domestic animals. The author explains in this paper how geographic distribution and familial occurrence of sarcoidosis as well as racial differences in the incidence of this disease, could be related to such findings.

Animals↗

The discovery of the causal agent of Minamata disease.

After the outbreak of an epidemic of a strange disease characterized by severe neurological signs in the small Japanese town of Minamata, a number of scientists in different disciplines were required to identify the causal agent. An account is given of the three-year program, with its disappointments and frustrations as a result of the limitations of knowledge of ecological principles and the absence of adequate techniques for detection and measurement. The lessons that have been learned on how toxic compounds can accumulate and concentrate in food chains are described as are the ecological contributions of environmentally safe waste disposal techniques. This article is based on the recollections of Dr. Shoji Kitamura, who contributed greatly to the discovery of the causative agent of Minamata disease.

Animals↗

Mapping quantitative trait loci in chickpea associated with time to flowering and resistance to Didymella rabiei the causal agent of Ascochyta blight.

Drought is the major constraint to chickpea (Cicer arietinum L.) productivity worldwide. Utilizing early-flowering genotypes and advancing sowing from spring to autumn have been suggested as strategies for drought avoidance. However, Ascochyta blight (causal agent: Didymella rabiei (Kov.) v. Arx.) is a major limitation for chickpea winter cultivation. Most efforts to introgress resistance to the pathogen into Kabuli germplasm resulted in relatively late flowering germplasm. With the aim to explore the feasibility of combining earliness and resistance, RILs derived from a cross between a Kabuli cultivar and a Desi accession were evaluated under field conditions and genotyped with SSR markers. Three quantitative trait loci (QTLs) with significant effects on resistance were identified: two linked loci located on LG4 in epistatic interaction and a third locus on LG8. Two QTLs were detected for time to flowering: one in LG1 and another on LG2. When resistance and time to flowering were analyzed together, the significance of the resistance estimates obtained for the LG8 locus increased and the locus effect on days to flowering, previously undetected, was significantly different from zero. The identification of a locus linked both to resistance and time to flowering may account for the correlation observed between these traits in this and other breeding attempts.

Agriculture↗

Inhibiting effects of resveratrol and its glucoside piceid against Venturia inaequalis, the causal agent of apple scab.

Resveratrol is a phytoalexin produced in different unrelated plant species such as grapevine and peanut. The effect of resveratrol and its glucoside trans-resveratrol-3-O-beta-D-glycopyranosid (piceid) against Venturia inaequalis, the causal agent of apple scab, was evaluated using a newly established test based on enzymatically isolated cuticular membranes (CMs) from apple (Malus domestica Borkh.) leaves. The test substances resveratrol and piceid were either sorbed to CMs before inoculation with spores or were applied simultaneously with the Venturia inaequalis spores to the CMs, and their effect on germination, appressoria formation, and penetration was examined. Resveratrol had no influence on spore germination but a significant inhibiting effect on penetration when applied simultaneously as well as before. A percentage inhibition of 89.7 +/- 11.5 and 61.8 +/- 35.1 was observed for simultaneous and preapplication, respectively. The resveratrol glucoside piceid had a significant inhibitory effect on germination and completely inhibited penetration of the fungus at concentrations between 200 and 400 microg mL(-1) when applied simultaneously with the spores to the CMs. On piceid-enriched CM (preapplication), spores germinated but penetration was inhibited nearly completely (96.1 +/- 5.1%). Thus, in vitro experiments showed that resveratrol and its glucoside in fact could contribute to improving the pathogen resistance of apple leaves.

Ascomycota↗

RNAi in the Rhizarian Phytopathogen Plasmodiophora brassicae: The Causal Agent of Clubroot Disease in Cruciferous Crops.

Although RNA interference (RNAi) is widespread and functionally important across eukaryotes, RNAi pathways are diverse or even lost in some lineages. Rhizaria represents a major and distinct eukaryotic supergroup that includes Plasmodiophora brassicae (Pb), the causal agent of cruciferous clubroot disease, yet RNAi in this lineage remains poorly understood. Here, we characterized an unusual RNAi pathway in Pb. Small RNA sequencing across five representative Pb life stages revealed abundant siRNAs and miRNAs characterized by a predominant 21-nt length, phased genomic distribution, 2-nt 3' overhangs, and a strong 5'-cytidine bias. Three Pb miRNAs were further validated by northern blotting and stem-loop RT-qPCR. Genome analysis identified two canonical AGO homologs, PbAGO1 and PbAGO2, but no Dicer homologs, except for an RNase III-containing Drosha-like protein, PbDRL. Functional analyses showed that PbAGO1 and PbAGO2 mediate gene silencing, whereas PbDRL is required for sRNA biogenesis. Further, the cell wall component chitin was identified from Pb zoosporangia during the early infection and RNAi interfering with its biosynthesis in transgenic plants of Arabidopsis and Brassica napus blocked Pb early infection and conferred broad-spectrum resistance. Our study uncovers an unusual RNAi pathway in Rhizaria and provides a promising strategy to control cruciferous clubroot disease.

Plasmodiophora brassicae↗

Infectious glomerulopathy induced by a defined agent (Schistosoma mansoni): progression despite early elimination of the causal agent.

Thirty Syrian golden hamsters were infected with Schistosoma mansoni and 10 were used as negative controls. Hamsters were infected by 50 cercaria; 15 were treated by praziquantil in doses of 100 mg/kg at 12, 13, 14 and 15 weeks postinfection, and 15 hamsters were left as positive control. Five from each subgroup were sacrificed at 24, 28 and 32 weeks postinfection. Animals were subjected to weekly analysis for total plasma protein, serum creatinine, albumin, cholesterol, 24-hour urine volume, and urinary total protein excretion. At the end point, animals were sacrificed and the mesenteric venous plexus was explored for adult worms. Kidney and liver specimens were examined by light microscopy, immunofluorescence microscopy, and electron microscopy. Complete parasite eradication was achieved in treated animals. Although there were significantly higher plasma total protein, albumin, and lower cholesterol in the treated group, there were no significant differences in proteinuria or renal histopathologic changes between treated and untreated animals. We conclude that in golden hamsters, with complete and early parasite eradication no regression occurs in S. mansoni-related nephropathy. Moreover, we suggest that in this glomerulopathy, short exposure to an antigen may be sufficient to set in motion a cascade of events which is irreversible and which leads to permanent glomerular damage.

Animals↗

Genomes of the ex-type strains of Elsinoë mangiferae and E. perseae, the causal agents of scab on mango and avocado.

Elsinoë species are slow-growing, hemibiotrophic to necrotrophic fungi that cause scab diseases on economically important fruit crops. Genome resources for many host-specific species remain limited. We report high-quality draft genome assemblies for the ex-type strains of Elsinoë mangiferae (CBS 226.50) and E. perseae (CBS 406.34), causal agents of mango and avocado scab, respectively. Among 5 approaches tested, a Nanopore-only NextDenovo assembly produced the most contiguous genomes, yielding 24.5 Mb (E. mangiferae) and 25.1 Mb (E. perseae) assemblies with 13 and 18 contigs, respectively, BUSCO completeness scores of ∼94%, and multiple putative telomere-to-telomere chromosomes. Gene prediction identified 9,134 and 9,243 genes, respectively. Functional annotation revealed enrichment of metabolic and regulatory pathways, including those involved in posttranslational modification, protein transport, and secondary metabolism. Carbohydrate-active enzyme repertoires were small but conserved, consistent with stealth pathogenicity strategies and low plant cell wall degradation. Both genomes encoded large secretomes (>850 proteins), diverse protease repertoires (>300 proteins), Ecp2-like effector proteins, and multiple biosynthetic gene clusters, including clusters with similarity to those associated with elsinochrome and ACT-toxin II biosynthesis, some of which may contribute to host-pathogen interactions and disease development. A large fraction of genes lacked functional characterization, suggesting incomplete databases and/or the presence of lineage-specific genes potentially involved in virulence or host adaptation. These genome resources fill critical gaps for underrepresented Elsinoë species and provide taxonomically anchored references essential for diagnostics, comparative genomics, and research into the molecular basis of host specificity and pathogenicity in scab-causing fungi.

Persea↗

First isolation of Mycoplasma capricolum subsp. capricolum, one of the causal agents of caprine contagious agalactia, on the island of Lanzarote (Spain).

During an unusually long period of bad weather, several outbreaks of caprine contagious agalactia (CCA) were reported in a number of flocks on the island of Lanzarote (Canary Islands, Spain). Clinical and subclinical mastitis in lactating goats and some cases of arthritis and pneumonia in kids were observed in the affected flocks. Mycoplasma capricolum subsp. capricolum was isolated as the main causal agent of the outbreaks, associated with M. mycoides subsp. mycoides "large colony type" (Mmm LC) in two flocks. This is the first report of an isolation of M. capricolum subsp. capricolum on the island of Lanzarote. The finding is of epidemiological importance and could complicate plans to control the disease. The significance of this mycoplasma species in association with CCA must now be studied in detail.

Animals↗

The causal agents of damping-off disease of buglosse from Iran.

Iran is considered a major genetic for medicinal plant in the world. Because of this significant diversity and historical background in identification and utilization to remedy human and animal diseases, export of medicinal plant can help to strengthen local as well as natural economy. Buglosse (Fig. 1) is one of the most important and common medicinal plants in Iran and exist as Echium amoneum and Borago officinalis. This work was conducted in order to identify the causal agent(s) of damping off disease in buglosse. Plant disease samples were taken from Esfahan and Tehran provinces. Symptoms on original plant including root, crown rot, dark tissue, pith and hallow root were collected in order to isolate disease agent(s). Symptomatic root and crown tissues after surface sterilization with 96% ethanol were transferred on to PDA and WA media and also on moist filter paper in petri dishes. Two fungal colonies grew from tissue segments and spore culture was subsequently purified. The fungal isolate identified as Rhizoctonia solani based on the following test. Hyphal tip was removed from colony margin placed on PDA and PSA media and incubated in dark. Colony diameter of one hundred hyphae measured and nucleus was stained according to Bandoni (1979), Kronland and Stanghellini (1988). It was observed that in each cell of hyphae there are more than two nuclei. Single spore culture were obtained from macroconidia of Fusarium isolate. After 24 hr of incubation, growing single spore were transferred to KCL medium to detect spore chains. Fungal isolates transferred to PSA and PDA media for sporulation. After 7 days colonies appeared as white cream to pinkish on top and cream to dark pink at the bottom of petri dish with abundant micro and macro conidia. Colonies were snow white, felting shape, with ample causal hyphae on PSA medium. On KCL medium, fungal growth was superficial and colonies were colorless with long macroconidia and individual sausage-shape macroconidia being thinner one side and having maximum four septa. Microconidia were long double compartment round on both side, straight to slightly curved. Base on morphology and dimension of conidia and production of chlamidospore the funguses identify as Fusarium solani.

Borago↗

Identification of human herpesvirus-6 as a causal agent for exanthem subitum.

A virus was isolated from the peripheral blood lymphocytes of patients with exanthem subitum, cultured successfully in cord blood lymphocytes, and shown to be antigenically related to human herpesvirus-6 (HHV-6). Morphological features, as studied by thin-section electronmicroscopy, resembled those of herpes group viruses. Convalescent-phase serum samples, tested against the new viral antigen and HHV-6 antigen, showed seroconversion. The results strongly suggest that the newly isolated virus is identical or closely related to HHV-6 and the causal agent for exanthem subitum.

Acute Disease↗

Meat wrapper's asthma: identification of the causal agent.

Meat wrapper's asthma is a typical example of occupational asthma due to emissions from chemical products. The authors report three new cases due to the use of the now classic meat packaging techniques in supermarkets. The chemical agents involved were identified. Inhalation tests have been carried out in one patient with the complete wrappings, i.e. the PVC film and the price labels, and separate tests were performed with eight additives of the PVC film, and with phthalic anhydride and di-cyclohexylphthalate emitted from heated price labels. These tests incriminate two products: phthalic anhydride seems to be the principal causal agent and epoxidized soybean oil can be suspected as a secondary agent causing this occupational asthma.

Adult↗

Influence of Hydrogen Peroxide upon Carbon Dioxide Photoassimilation in the Spinach Chloroplast: I. HYDROGEN PEROXIDE GENERATED BY BROKEN CHLOROPLASTS IN AN "INTACT" CHLOROPLAST PREPARATION IS A CAUSAL AGENT OF THE WARBURG EFFECT.

Photosynthesis and the Warburg effect (O(2) inhibition of photosynthesis) were evaluated in preparations of intact spinach chloroplasts enriched with varying amounts of lysed chloroplasts. Increasing the ratio of broken to intact plastids resulted in decreased rates of CO(2) assimilation.Hydrogen peroxide when added at 10 or more micromolar also inhibited photosynthesis in these preparations. Inhibition of the photosynthetic rate by both factors was eliminated by addition of catalase. These findings indicate that H(2)O(2) presumably generated by the broken chloroplasts was the causal agent of this inhibition.The Warburg effect also became more pronounced by increasing the level of broken to intact chloroplasts. This effect was examined as a function of added catalase, pH, and O(2) concentration. At 21% O(2) and 0.44 to 0.68 millimolar CO(2), catalase relieved the effect almost completely at pH 7.5, but at pH 8.3, the rate was restored only to about half or less of the control. At pH 7.6, 0.44 millimolar CO(2), and 100% O(2), the effect was only slightly overcome by catalase.A rise in glycolate synthesis by the isolated spinach chloroplast has been shown previously to be coupled to an increase in pH and O(2) (Kow, Robinson, Gibbs 1977 Plant Physiol 60: 492-495; Robinson, Gibbs, Cotler 1977 Plant Physiol 59: 530-534). At 21% O(2), glycolate synthesis was not affected by the addition of catalase at pH 7.5 or 8.3. It is proposed that at 21% O(2) and without some means of removing H(2)O(2), that portion of the Warburg effect attributed to glycolate synthesis has been overestimated at pH values in the order of 7.5. In contrast, that portion of the Warburg effect which was, at alkaline pH, insensitive to catalase represented the stress placed upon the photosynthetic carbon reduction cycle which resulted from an enhanced synthesis of glycolate. At 100% O(2) aeration and pH 7.5 to 8.5, the Warburg effect may also represent O(2)-mediated inhibition of a Calvin cycle enzyme within the intact plastid.

Journal Article↗

[Borrelia burgdorferi may be the causal agent of sarcoidosis].

Serum antibody to Borrelia burgdorferi was measured in 33 patients with sarcoidosis who were confirmed clinically and pathologically. The results showed that 81.8% of the patients were positive. In addition, a strain of Borrelia burgdorferi was isolated from a patient's blood. Fourteen patients received ceftriaxone 2 g per day and/or penicillin 12 million per day and a patient received lincomycin 1.2 g per day. The antibody titer of the patients turned to normal level, their SACE turned to normal range, and chest X-ray findings were markedly improved in 3 cases after the treatment. According to the facts mentioned above, we consider that Borrelia burgdorferi may be the causal agent of sarcoidosis and sarcoidosis might be a special type of Lyme disease.

Adult↗

Infectious cDNA clone used to identify strawberry mild yellow edge-associated potexvirus as causal agent of the disease.

A full-length in vivo infectious cDNA clone of strawberry mild yellow edge-associated potexvirus (SMYEaV) was constructed and used to inoculate Fragaria vesca 'Alpine' seedlings and Rubus rosifollus. Both host plants could be infected using particle bombardment or agroinoculation, but not by mechanical inoculation. A method that used potted strawberry plants for particle bombardment resulted in high survival and infection rates. The plants developed systemic infection and virus particles were detected by ELISA and immunoelectron microscopy. Mechanical inoculation of Chenopodium quinoa and C. foetidum with the 35S construct resulted in localized infections. F. vesca 'Alpine' indicator plants produced symptoms that were indistinguishable from control plants inoculated with a naturally occurring isolate of strawberry mild yellow edge by graft or aphid transmission. These results suggest that SMYE potexvirus is the causal agent of strawberry mild yellow edge disease. As this virus is capable of causing the disease, we propose the name strawberry mild yellow edge potexvirus, with the acronym SMYEPV, to replace the name strawberry mild yellow edge-associated potexvirus.

Animals↗

A rapid molecular assay for the detection of antibiotic resistance determinants in causal agents of infective endocarditis.

AIMS: To develop and employ a PCR amplification system, directly from clinical specimens, for the rapid molecular detection of common antimicrobial resistance genes for streptococci, staphylococci and enterococci organisms causing infective endocarditis (IE). METHODS AND RESULTS: Eleven antibiotic resistance genes were targeted by PCR along with four identification-related loci. Blood culture and heart valve material from staphylococcal endocarditis patients were directly examined for methicillin resistance. PCR conditions were optimized for the following antibiotic resistance loci: staphylococci (mecA, aacA-aphD), streptococci (PBP 1A, PBP 2B, gyrB, parE) and enterococci (vanA, vanB, vanC-1, vanC-2, aacA-aphD, aphA3). The presence of methicillin resistance was confirmed in one of the eight IE patients examined. CONCLUSION: This study presents a PCR amplification system for the detection of antibiotic resistance genes. Detection of such genes may indicate susceptibility of the causal agents of IE to commonly prescribed antimicrobial agents. SIGNIFICANCE AND IMPACT OF THE STUDY: Rapid detection of antibiotic resistant organisms may reduce the use of inappropriate antibiotic agents or enable the use of the most appropriate combinations of antibiotics, other than those that would normally be prescribed empirically for IE. Such a method may be particularly valuable in cases of culture-negative endocarditis. Detection of antibiotic resistance genes by molecular-based techniques, namely PCR, will allow more directed antibiotic therapy and may also provide opportunities for earlier identification of resistant organisms.

Drug Resistance, Microbial↗

Is Helicobacter pylori a causal agent in gastric carcinoma?

The aim of this study is to clarify the relationship between Helicobacter pylori (H. pylori) infection and gastric carcinoma. 94 patients with gastric carcinoma and 111 patients with chronic gastritis were involved in this study. They were classified into 3 age groups: Group A (40 years and under), Group B (41-59), Group C (60 years and over). Serum samples were tested for H. pylori IgG antibodies by ELISA and for pepsinogen (PG) by RIA. The ratio of PG I/PG II was used as a marker for atrophic gastritis. Results were as follows. In the incidence of H. pylori antibodies, there was no significant differences between gastric carcinoma and chronic gastritis in any of the groups. In the quantity of H. pylori antibodies, there was no significant difference between gastric carcinoma and chronic gastritis in any of the groups. The ratio of PG I/PG II was significantly decreased in H. pylori positive cases when compared to H. pylori negative cases in each group with chronic gastritis and group A and B with gastric carcinoma. The ratio of PG I/PG II in gastric carcinoma was significantly lower than that of chronic gastritis. As conclusion, from the point of view of the prevalence of H. pylori, it is suggested that H. pylori is not a direct causal agent in the pathogenesis of gastric carcinoma.

Adult↗