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PubMed2005

Transmission of bovine viral diarrhea virus 1b to susceptible and vaccinated calves by exposure to persistently infected calves.

Bovine viral diarrhea virus (BVDV) persistently infected (PI) calves represent significant sources of infection to susceptible cattle. The objectives of this study were to determine if PI calves transmitted infection to vaccinated and unvaccinated calves, to determine if BVDV vaccine strains could be differentiated from the PI field strains by subtyping molecular techniques, and if there were different rates of recovery from peripheral blood leukocytes (PBL) versus serums for acutely infected calves. Calves PI with BVDV1b were placed in pens with nonvaccinated and vaccinated calves for 35 d. Peripheral blood leukocytes, serums, and nasal swabs were collected for viral isolation and serology. In addition, transmission of Bovine herpes virus 1 (BHV-1), Parainfluenza-3 virus (PI-3V), and Bovine respiratory syncytial virus (BRSV) was monitored during the 35 d observation period. Bovine viral diarrhea virus subtype 1b was transmitted to both vaccinated and nonvaccinated calves, including BVDV1b seronegative and seropositive calves, after exposure to PI calves. There was evidence of transmission by viral isolation from PBL, nasal swabs, or both, and seroconversions to BVDV1b. For the unvaccinated calves, 83.2% seroconverted to BVDV1b. The high level of transmission by PI calves is illustrated by seroconversion rates of nonvaccinated calves in individual pens: 70% to 100% seroconversion to the BVDV1b. Bovine viral diarrhea virus was isolated from 45 out of 202 calves in this study. These included BVDV1b in ranch and order buyer (OB) calves, plus BVDV strains identified as vaccinal strains that were in modified live virus (MLV) vaccines given to half the OB calves 3 d prior to the study. The BVDV1b isolates in exposed calves were detected between collection days 7 and 21 after exposure to PI calves. Bovine viral diarrhea virus was recovered more frequently from PBL than serum in acutely infected calves. Bovine viral diarrhea virus was also isolated from the lungs of 2 of 7 calves that were dying with pulmonary lesions. Two of the calves dying with pneumonic lesions in the study had been BVDV1b viremic prior to death. Bovine viral diarrhea virus 1b was isolated from both calves that received the killed or MLV vaccines. There were cytopathic (CP) strains isolated from MLV vaccinated calves during the same time frame as the BVDV1b isolations. These viruses were typed by polymerase chain reaction (PCR) and genetic sequencing, and most CP were confirmed as vaccinal origin. A BVDV2 NCP strain was found in only 1 OB calf, on multiple collections, and the calf seroconverted to BVDV2. This virus was not identical to the BVDV2 CP 296 vaccine strain. The use of subtyping is required to differentiate vaccinal strains from the field strains. This study detected 2 different vaccine strains, the BVDV1b in PI calves and infected contact calves, and a heterologous BVDV2 subtype brought in as an acutely infected calf. The MLV vaccination, with BVDV1a and BVDV2 components, administered 3 d prior to exposure to PI calves did not protect 100% against BVDV1b viremias or nasal shedding. There were other agents associated with the bovine respiratory disease signs and lesions in this study including Mannheimia haemolytica, Mycoplasma spp., PI-3V, BRSV, and BHV-1.

Animals↗
PubMed1994

Restriction fragment length polymorphism analysis of clinical isolates of Mycobacterium haemophilum.

Mycobacterium haemophilum is an emerging opportunistic pathogen, and since 1989, infections caused by this organism have been identified more frequently in the New York City area than in any other region of the United States. A DNA fingerprinting method, based on restriction fragment length polymorphisms (RFLPs) was developed. A genomic library of M. haemophilum isolate 1A was constructed; screening the library yielded a recombinant strain that incorporated a genetic element present in multiple copies in the M. haemophilum genome. This clone was used to produce a probe for RFLP analyses of PvuII digests of genomic DNA. We used this probe to determine the RFLP patterns of 43 clinical isolates of M. haemophilum from 28 patients. A total of six distinct patterns were observed. Two patterns, designated types 1 and 2, accounted for 91% of the infections in patients from the New York City area. Two isolates from Arizona had identical patterns but were distinct from those of New York isolates, and an isolate from Israel, the type strain, had another distinct pattern (type 6). The type 6 pattern was also seen in a recent isolate from Norway. All of the type 1 isolates and 60% of the type 2 isolates were recovered from patients with AIDS in the New York City area. This molecular subtyping method should provide a useful tool for epidemiological studies and may help identify the associated risk factors, vehicles, and possible reservoirs of this newly emerging pathogen.

AIDS-Related Opportunistic Infections↗
PubMed2026

SWI/SNF Alterations Define a Chromatin-Dependent Subtype of Urothelial Carcinoma.

PURPOSE: SWI/SNF (BAF) chromatin remodeling complex alterations are common in urothelial carcinoma, yet no biomarker-directed therapeutic strategies have been established for this population. We investigated whether BAF alterations delineate a biologically distinct, therapeutically actionable urothelial carcinoma subtype. EXPERIMENTAL DESIGN: We performed integrative genomic and transcriptomic analyses of 792 urothelial carcinoma tumors from the Oncology Research Information Exchange Network (ORIEN) and validated findings in the TCGA-BLCA cohort. Mechanistic studies incorporated RNA sequencing and ATAC-seq following histone deacetylase (HDAC) inhibition. Functional dependencies were assessed using patient-derived xenograft organoids and cell line models. Clinical relevance was explored in a biomarker-enriched investigator-initiated trial. RESULTS: Approximately half of urothelial carcinoma tumors exhibited BAF alterations, defining a previously unrecognized chromatin-altered molecular subtype characterized by activation of proliferative programs, loss of lineage identity, and altered metabolic signaling. This subtype was enriched for transcriptomic programs associated with HDAC inhibitor sensitivity and depleted of HDAC inhibitor resistance signatures. Mechanistically, HDAC inhibition induced widespread chromatin remodeling with reduced accessibility at AP-1 and TEAD-associated regions, and downregulation of E2F- and MYC-driven transcriptional networks. Functional studies confirmed enhanced HDAC inhibition sensitivity in ARID1A -mutated cell lines and a patient-derived organoid model. Early clinical observations demonstrated a durable responder treated with HDAC inhibitors and immunotherapy. CONCLUSIONS: BAF alterations define a chromatin-dependent tumor state in urothelial carcinoma that is selectively vulnerable to HDAC inhibition. Integrating genomic, epigenomic, functional, and early clinical evidence, these findings provide a rationale for biomarker-enriched clinical trials and HDAC inhibitor-based combination strategies in urothelial carcinoma.

Journal Article↗
PubMed2026

Integrative subtyping by bile acid metabolism identifies CLCA1/UGT2A3/ZG16 as markers of immune dysfunction and poor prognosis in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is the primary driver of cancer-related death and illness across the world. Despite the full-scale shift of the treatment approach for some colorectal cancer patients due to the use of immune checkpoint inhibitors (ICIs), primary resistance still poses a huge challenge to clinicians. Bile acid metabolism is involved in the pathogenesis of CRC. However, its particular function in shaping the tumor immune microenvironment (TIME) and its effect on prognosis and immune treatment response remain unclear. METHODS: Based on the transcriptome and clinical data from The Cancer Genome Atlas-Colon Adenocarcinoma (TCGA-COAD) cohort, we performed unsupervised consensus clustering and classified patients into different molecular subtypes according to bile acid metabolism. We subsequently compared overall survival (OS), immune cell infiltration levels, and differentially expressed genes among the subtypes. In addition, protein-protein interaction (PPI) network and Cox proportional hazards regression were used to identify key hub genes. Finally, the expression of these crucial hub genes was validated in the Gene Expression Omnibus (GEO) cohort and independent clinical patients. RESULTS: The bile-low group showed a significant reduction in OS time (p = 0.0049). The infiltration levels of CD8+ T cells (p < 0.05) and M1 macrophages (p < 0.01) were significantly higher in the bile-low group than in the bile-high group. We identified three key genes-CLCA1, UGT2A3, and ZG16-and found that they all were downregulated in tumor tissues across the TCGA-COAD and GEO datasets, as well as in independent clinical samples. Survival analysis showed that high CLCA1 expression was significantly associated with favorable overall survival (p < 0.001), whereas UGT2A3 (p = 0.23) and ZG16 (p = 0.17) did not reach statistical significance. The three hub genes were negatively correlated with the (TIDE) score (CLCA1: R = - 0.24, p < 0.001; UGT2A3: R = - 0.15, p = 0.0022; ZG16: R = - 0.14, p = 0.0039). CONCLUSION: Our findings suggest that bile acid metabolism could shape the TIME via key genes CLCA1, UGT2A3, and ZG16, and subsequently modify CRC prognosis and immunotherapy responses. These genes may serve as potential prognostic indicators and mechanistic mediators linking bile acid metabolism to T-cell dysfunction, offering insights for future combination strategies targeting the metabolism-barrier-immunity axis.

CLCA1↗
PubMed2004

Use of gene-expression profiling to identify prognostic subclasses in adult acute myeloid leukemia.

BACKGROUND: In patients with acute myeloid leukemia (AML), the presence or absence of recurrent cytogenetic aberrations is used to identify the appropriate therapy. However, the current classification system does not fully reflect the molecular heterogeneity of the disease, and treatment stratification is difficult, especially for patients with intermediate-risk AML with a normal karyotype. METHODS: We used complementary-DNA microarrays to determine the levels of gene expression in peripheral-blood samples or bone marrow samples from 116 adults with AML (including 45 with a normal karyotype). We used unsupervised hierarchical clustering analysis to identify molecular subgroups with distinct gene-expression signatures. Using a training set of samples from 59 patients, we applied a novel supervised learning algorithm to devise a gene-expression-based clinical-outcome predictor, which we then tested using an independent validation group comprising the 57 remaining patients. RESULTS: Unsupervised analysis identified new molecular subtypes of AML, including two prognostically relevant subgroups in AML with a normal karyotype. Using the supervised learning algorithm, we constructed an optimal 133-gene clinical-outcome predictor, which accurately predicted overall survival among patients in the independent validation group (P=0.006), including the subgroup of patients with AML with a normal karyotype (P=0.046). In multivariate analysis, the gene-expression predictor was a strong independent prognostic factor (odds ratio, 8.8; 95 percent confidence interval, 2.6 to 29.3; P<0.001). CONCLUSIONS: The use of gene-expression profiling improves the molecular classification of adult AML.

Acute Disease↗
PubMed1994

Application of subtyping by combined allozyme, whole-cell protein and antibiotic resistance analysis in epidemiological investigations of food-borne infections.

Allozyme pattern, whole-cell protein pattern and antibiotic resistance were used as markers for epidemiological subtyping (below the species level) of food-relevant bacteria. The results of this study confirm the applicability of these patterns as epidemiological markers also for this special purpose. Electrotyping using also a reduced allozyme set seems to be the method with the highest discriminatory power of the three methods evaluated. Several examples demonstrate that complex typing of bacteria based on a combination of these three methods is useful for the analysis of food-borne infections and establishment of their causes but also for zoonotic studies. We see, beyond this, further applications of molecular subtyping methods in food microbiology and food hygiene such as safety checking in food industry or monitoring in biotechnological processes.

Bacterial Proteins↗
PubMed2026

Proteogenomic features define subtypes of mantle cell lymphoma.

Mantle cell lymphoma (MCL) is a biologically heterogeneous B-cell malignancy. Although genomics and transcriptomics have delineated parts of the MCL disease spectrum, proteomics remains largely unexplored. Here, we conducted a comprehensive proteogenomic analysis integrating genomics, transcriptomics, and proteomics on peripheral blood samples from 27 patients with MCL and 4 healthy donors to investigate the translational and posttranslational dimensions of MCL. Our study identified 1296 downregulated and 468 upregulated proteins in MCL cells. The splicing pathways were significantly upregulated at both the mRNA and protein levels, suggesting a critical role for aberrant RNA splicing in MCL pathogenesis. Integration of proteomic data with genetic aberrations revealed immunoglobulin heavy chain variable mutational status and CCND1 mutation are associated with distinctive transcriptomic and proteomic profiles, which correspond to significant differences in clinical outcomes. A multiomics molecular stratification model incorporating proteomic data showed superior predictive power for patient survival compared with single-omics models (concordance index, 0.83 vs 0.74). This study provides, to our knowledge, the first comprehensive proteogenomic profile of MCL, offering novel insights into its molecular mechanisms and clinical behavior. The identification of molecular subtypes and prognostic protein signatures underscores the potential of proteomics to guide precision medicine strategies for MCL.

Humans↗
PubMed2026

Yes-Associated Protein (YAP)1 and &#x3b2;-Catenin Immunohistochemistry as a Surrogate Marker for GTF2I-Mutant Type A/AB Thymomas.

Thymomas are rare thymic epithelial tumors classified by the World Health Organization into type A/AB thymomas, which commonly harbor GTF2I mutations and behave indolently, and type B thymomas and thymic carcinomas, in which these mutations are less common. Type A and AB thymomas are uniquely enriched for a recurrent somatic hotspot mutation in GTF2I p. L424H; yet, this gene is rarely included in clinical sequencing panels, limiting its diagnostic utility. Yes-associated protein (YAP)1, the principal effector of the Hippo signaling pathway, and &#x3b2;-catenin, the central transcriptional effector of the Wnt pathway, have emerging roles in thymoma biology; however, their relationship to GTF2I mutation status and histologic subtype has not been systematically characterized. We analyzed The Cancer Genome Atlas thymoma data set and an institutional cohort of 38 thymic epithelial tumors to evaluate YAP1 and &#x3b2;-catenin immunohistochemistry (IHC) as surrogate markers for GTF2I mutation status and histologic classification. In The Cancer Genome Atlas data set, YAP1 and CTNNB1 mRNA expression were markedly elevated in type A/AB thymomas relative to type B and carcinoma subtypes, and GTF2I-mutant tumors exhibited significantly higher YAP1 mRNA expression than GTF2I-wildtype tumors. Targeted next-generation sequencing of our institutional cohort confirmed enrichment of the canonical GTF2I p. L424H hotspot in indolent subtypes. By IHC, both nuclear YAP1 positivity and cytoplasmic &#x3b2;-catenin localization were significantly more frequent in indolent thymomas. Cytoplasmic &#x3b2;-catenin demonstrated high specificity (94%) for indolent histology, supporting its use in diagnostically challenging cases such as type A versus type B3 distinction on small biopsies. YAP1 IHC showed a high negative predictive value for GTF2I mutations, such that a YAP1-negative result reliably excludes a GTF2I-mutant tumor. These findings implicate crosstalk between Hippo and Wnt signaling in GTF2I-mutant thymomas and position YAP1 and &#x3b2;-catenin IHC as accessible, cost-effective surrogates for molecular subtyping in a tumor where standard sequencing panels have limited coverage.

GTF2I↗
PubMed2026

[BRCA1 Gene's Mutations And Hereditary Breast Cancer: Genetic, Biological, And Clinical Aspects].

INTRODUCTION: Hereditary breast cancer accounts for approximately 5 to 10% of all breast cancer cases. Mutations in the BRCA1 gene, which plays a central role in DNA repair and cell cycle regulation, are the main cause of these familial forms and are strongly associated with aggressive subtypes, particularly triple-negative breast cancer. METHODS: A narrative literature review was conducted using biomedical databases (PubMed, Scopus, Web of Science, Google Scholar) between January 2024 and June 2025. Eligible publications addressed the genetic, biological, epidemiological, and clinical aspects of BRCA1 in hereditary breast cancer. RESULTS: BRCA1 ensures genomic stability through its roles in DNA repair, cell cycle checkpoints, and transcriptional regulation. Most mutations are truncating or missense variants, with some reported as founder mutations (e.g., c.68_69delAG, c.5266dupC, 943ins10). Women carrying germline BRCA1 mutations have an estimated lifetime risk of 56-87% of developing breast cancer, with a strong association with aggressive molecular subtypes, especially triple-negative breast cancer. CONCLUSION: A comprehensive understanding of BRCA1 mutations is crucial to enhance prevention, screening, and personalized management of hereditary breast cancer. In low-resource settings, the integration of genetic testing and counseling remains a major challenge and a public health priority to reduce disparities in cancer care.

Humans↗
PubMed1988

Comparison of molecular methods for subtyping patients and epidemiologically linked environmental isolates of Legionella pneumophila.

We used the molecular techniques of monoclonal antibody typing, plasmid analysis, and outer membrane protein profiling to subtype 159 patients' and environmental (water distribution system) isolates of Legionella pneumophila serogroup 1 from 18 institutions. The ability of these techniques to match patients' and epidemiologically linked environmental isolates from outbreaks of Legionnaires' disease at seven institutions was also compared. Two different panels of monoclonal antibodies (I and II) identified nine subtypes (one new disease-causing subtype) and six subtypes, respectively. The Bellingham 1 subtype type was the most common among environmental isolates, and the Philadelphia 1 subtype predominated among patients' isolates from all institutions except the Veterans Administration Medical Center in Pittsburgh, Pennsylvania. The source of an isolate (patient vs. environment) and its monoclonal antibody subtype were significantly associated (P less than .01). With use of the molecular techniques tested, the subtypes of patients' isolates were identical to those of epidemiologically linked environmental isolates from the same hospital.

Antibodies, Monoclonal↗
PubMed2005

Outbreak of osteomyelitis/septic arthritis caused by Kingella kingae among child care center attendees.

OBJECTIVE: Kingella kingae often colonizes the oropharyngeal and respiratory tracts of children but infrequently causes invasive disease. In mid-October 2003, 2 confirmed and 1 probable case of K kingae osteomyelitis/septic arthritis occurred among children in the same 16- to 24-month-old toddler classroom of a child care center. The objective of this study was to investigate the epidemiology of K kingae colonization and invasive disease among child care attendees. METHODS: Staff at the center were interviewed, and a site visit was performed. Oropharyngeal cultures were obtained from the staff and children aged 0 to 5 years to assess the prevalence of Kingella colonization. Bacterial isolates were subtyped by pulsed-field gel electrophoresis (PFGE), and DNA sequencing of the 16S rRNA gene was performed. A telephone survey inquiring about potential risk factors and the general health of each child was also conducted. All children and staff in the affected toddler classroom were given rifampin prophylaxis and recultured 10 to 14 days later. For epidemiologic and microbiologic comparison, oropharyngeal cultures were obtained from a cohort of children at a control child care center with similar demographics and were analyzed using the same laboratory methods. The main outcome measures were prevalence and risk factors for colonization and invasive disease and comparison of bacterial isolates by molecular subtyping and DNA sequencing. RESULTS: The 2 confirmed case patients required hospitalization, surgical debridement, and intravenous antibiotic therapy. The probable case patient was initially misdiagnosed; MRI 16 days later revealed evidence of ankle osteomyelitis. The site visit revealed no obvious outbreak source. Of 122 children in the center, 115 (94%) were cultured. Fifteen (13%) were colonized with K kingae, with the highest prevalence in the affected toddler classroom (9 [45%] of 20 children; all case patients tested negative but had received antibiotics). Six colonized children were distributed among the older classrooms; 2 were siblings of colonized toddlers. No staff (n = 28) or children aged <16 months were colonized. Isolates from the 2 confirmed case patients and from the colonized children had an indistinguishable PFGE pattern. No risk factors for invasive disease or colonization were identified from the telephone survey. Of the 9 colonized toddlers who took rifampin, 3 (33%) remained positive on reculture; an additional toddler, initially negative, was positive on reculture. The children of the control child care center demonstrated a similar degree and distribution of K kingae colonization; of 118 potential subjects, 45 (38%) underwent oropharyngeal culture, and 7 (16%) were colonized with K kingae. The highest prevalence again occurred in the toddler classrooms. All 7 isolates from the control facility had an indistinguishable PFGE pattern; this pattern differed from the PFGE pattern observed from the outbreak center isolates. 16S rRNA gene sequencing demonstrated that the outbreak K kingae strain exhibited >98% homology to the ATCC-type strain, although several sequence deviations were present. Sequencing of the control center strain demonstrated more homology to the outbreak center strain than to the ATCC-type strain. CONCLUSIONS: This is the first reported outbreak of invasive K kingae disease. The high prevalence in the affected toddler class and the matching PFGE pattern are consistent with child-to-child transmission within the child care center. Rifampin was modestly effective in eliminating carriage. DNA sequence analysis suggests that there may be considerable variability within the species K kingae and that different K kingae strains may demonstrate varying degrees of pathogenicity.

Anti-Bacterial Agents↗
PubMed1999

Analysis of Huntingtin-associated protein 1 in mouse brain and immortalized striatal neurons.

Huntingtin, the protein product of the Huntington's disease (HD) gene, is expressed with an expanded polyglutamine domain in the brain and in nonneuronal tissues in patients with HD. Huntingtin-associated protein 1 (HAP-1), a brain-enriched protein, interacts preferentially with mutant huntingtin and thus may be important in HD pathogenesis. The function of HAP-1 is unknown, but recent evidence supports a role in microtubule-dependent organelle transport. We examined the subcellular localization of HAP-1 with an antibody made against the NH2-terminus of the protein. In immunoblot assays of mouse brain and immortalized striatal neurons, HAP-1 subtypes A and B migrated together at about 68 kD and separately at 95 kD and 110 kD, respectively. In dividing clonal striatal cells, HAP-1 localized to the mitotic spindle apparatus, especially at spindle poles and on vesicles and microtubules of the spindle body. Postmitotic striatal neurons had punctate HAP-1 labeling throughout the cytoplasm. Western blot analysis of protein extracts obtained after subcellular fractionation and differential centrifugation of the clonal striatal cells showed that HAP-1B was preferentially enriched in membrane fractions. Electron microscopic study of adult mouse basal forebrain and striatum showed HAP-1 localized to membrane-bound organelles including large endosomes, tubulovesicular structures, and budding vesicles in neurons. HAP-1 was also strongly associated with an unusual large "dense" organelle. Microtubules were labeled in dendrites and axonal fibers. Results support a role for HAP-1 in vesicle trafficking and organelle movement in mitotic cells and differentiated neurons and implicate HAP-1B as the predominant molecular subtype associated with vesicle membranes in striatal neurons.

Animals↗
PubMed2006

Outbreaks of avian cholera in Hope Bay, Antarctica.

During austral summers 1999-2000 and 2000-01, two outbreaks of avian cholera occurred in the Hope Bay area (63 degrees 24'S, 56 degrees 59'W), located on the tip of the Antarctic Peninsula. Eighty-six dead birds were found: five kelp gulls (Larus dominicanus), 36 skuas (Stercorarius sp.), and 45 Adelie penguins (Pygoscelis adeliae). The carcasses were studied using clinical, pathological, and microbiological criteria. Water samples from ponds where birds were settled and samples from 90 healthy birds also were analyzed during the second outbreak. Pasteurella multocida isolates were identified by biochemical tests, capsular type, somatic serotype, and susceptibility to nine antibiotics. Molecular subtyping was performed by ApaI and SmaI pulsed-field gel electrophoresis (PFGE) and enterobacterial repetitive intergenic consensus (ERIC-PCR). In February 2000, mortality in skuas was 16% and 2% in kelp gulls. In the 2000-01 breeding season, mortality in south polar skuas was 47%, 24% in brown skuas, 1.4% in kelp gulls, and 0.01% in Adelie penguins. All birds had lesions of avian cholera. In kelp gulls the presentation was chronic, whereas skuas and penguins suffered subacute and acute disease, respectively. Fifty-five isolates recovered from dead birds and one from water were identified as P. multocida gallicida, type A:1. The strains presented a unique molecular pattern by PFGE and ERIC-PCR. A possible hypothesis to explain the origin of the outbreaks was that nonbreeder kelp gulls carried P. multocida gallicida to Hope Bay, and avian cholera was transmitted through water to skuas and penguins. This study reports avian cholera in new bird species, their potential role in the transmission of the disease, and the different responses of these species to the disease.

Animals↗
PubMed2004

A multistate outbreak of Escherichia coli O157:H7 infection linked to consumption of beef tacos at a fast-food restaurant chain.

We investigated a multistate outbreak of Escherichia coli O157:H7 infections. Isolates from 13 case patients from California, Nevada, and Arizona were matched by pulsed-field gel electrophoresis subtyping. Five case patients (38%) were hospitalized, and 3 (23%) developed hemolytic uremic syndrome; none died. The median age was 12 years (range, 2-75 years), and 10 (77%) were female. Case-control studies found an association between illness and eating beef tacos at a national Mexican-style fast-food restaurant chain (88% of cases versus 38% of controls; matched OR, undefined; 95% confidence interval, 1.49 to infinity; P=.009). A trace-back investigation implicated an upstream supplier of beef, but a farm investigation was not possible. This outbreak illustrates the value of employing hospital laboratory-based surveillance to detect local clusters of infections and the effectiveness of using molecular subtyping to identify geographically dispersed outbreaks. The outbreak investigation also highlights the need for a more efficient tracking system for food products.

Adolescent↗
PubMed2005

Necrotizing enterocolitis associated with clostridium perfringens type A in previously healthy north american adults.

BACKGROUND: Necrotizing enteritis associated with Clostridium perfringens type C ("pigbel") is a well-known syndrome in severely protein-deprived populations in the Pacific. It is exceedingly rare in the developed world. C perfringens type A is a common cause of acute gastroenteritis and, in a handful of infections, has been reported in association with a syndrome resembling necrotizing enteritis. STUDY DESIGN: This study includes a case series and literature review. Charts and autopsy reports from four patients with adult necrotizing enterocolitis (ANEC) were reviewed. C perfringens isolates were subtyped by mouse bioassay and pulsed-field gel electrophoresis. Fixed tissue specimens were tested with an anticlostridial antibody using an immunohistochemical assay. RESULTS: Between 2000 and 2003, ANEC developed in four previously healthy men; three died. The small bowel was affected in three patients and the colon in two patients. Portal or mesenteric vein thrombosis occurred in three patients. C perfringens type A was isolated from three patients and immunohistochemical assay demonstrated clostridial antigens limited to affected areas of the intestine of all four. The nonculture positive patient had a strong epidemiologic link to one of the others, and a compatible clinical course. C perfringens of the same pulsed-field gel electrophoresis-defined molecular subtyped was isolated from stool samples of one patient, his wife, and food from a restaurant they patronized. CONCLUSIONS: ANEC associated with C perfringens type A infection occurred in four North American adults. Culture for C perfringens type A should be performed in cases of ANEC. Alternative tests such as immunohistochemical assay were diagnostically useful. Additional research might uncover virulence factors, host factors, and the burden of disease in the population.

Adult↗
PubMed2004

Patterns of large-scale genomic variation in virulent and avirulent Burkholderia species.

The human diseases melioidosis and glanders are caused by the bacteria Burkholderia pseudomallei and B. mallei respectively, and both species are regarded as potential biowarfare agents. We used B. pseudomallei DNA microarrays to compare the genomes of several clinical and environmental isolates of B. pseudomallei, B. mallei, and B. thailandensis, a closely related but avirulent species. Open reading frames (ORFs) deleted between the three species were associated with diverse cellular functions, including nitrogen and iron metabolism, quorum sensing, and polysaccharide production. Deleted ORFs in B. mallei exhibited significant genomic clustering, whereas deletions in B. thailandensis were more uniformly dispersed, suggesting that B. mallei and B. thailandensis may have diverged from B. pseudomallei and each other via distinct mechanisms. The genomes of independent B. pseudomallei isolates were highly conserved with a large-scale variance of less than 3% between isolates, and at least three distinct molecular subtypes could be defined. An analysis of subtype-specific genomic regions suggests that DNA loss has played an important role in the evolutionary radiation of B. pseudomallei in the natural environment. Our results raise several hypotheses concerning the possible mechanisms underlying the diverse biological properties exhibited by members of the Burkholderia family.

Bacterial Typing Techniques↗
PubMed1999

Arbitrarily primed-polymerase chain reaction for identification and epidemiologic subtyping of oral isolates of Fusobacterium nucleatum.

BACKGROUND: Fusobacterium nucleatum is the most frequently isolated bacterium in periodontal disease and plays an important role in serious infections in other parts of the body. Arbitrarily primed-polymerase chain reaction (AP-PCR) was used to construct primers for specific identification and subtyping of F. nucleatum. Subtypes may differ in virulence and, hence, are important as periodontal pathogens. Subtypes also may differ in antibiotic susceptibility; therefore, knowing the subtypes may influence choice of treatment. METHODS: We analyzed 70 DNA samples of F. nucleatum isolated from patients with periodontal disease (PD) (N = 32) or AIDS-related PD (N = 8) and from healthy carriers (N = 30). From 90 AP-PCR primers screened, five amplification products were selected, cloned in pCR II vector, and sequenced. These sequences were used to design new pairs of specific primers. Sequences were compared to GenBank entries with BLAST and showed no significant matches. RESULTS: Three primer pairs produced bands of approximately 1 Kb (primer 5059S) or 0.5 Kb (primers FN5047 or M1211) with all F. nucleatum DNAs tested. PCR amplification using primer pair M8171 produced a 1 Kb band with isolates from 7 (22%) PD and 5 (63%) PD-AIDS patients and 9 (30%) healthy controls. Using the same primer pair, 2 other bands of approximately 0.5 Kb and 0.4 Kb were observed with DNA from isolates from 2 (6%) PD and all PD-AIDS patients, but were not observed with DNA samples from healthy controls (P<0.0001). All the primer pairs produced no or different amplicon profiles with DNA samples from bacterial species other than F. nucleatum. CONCLUSIONS: Our results suggest that PCR primer pairs 5059S, FN5047 or M1211 can be used to specifically identify F. nucleatum isolates and distinguish them from other bacteria. The primer pair M8171 could also be used to differentiate F. nucleatum isolated from periodontal patients or healthy individuals. These specific primers can be used in PCR analysis for specific identification of F. nucleatum and to distinguish it from other bacteria associated with human periodontitis. These approaches appear promising in facilitating laboratory identification, molecular subtyping, and taxonomy of putative periodontopathogens.

AIDS-Related Opportunistic Infections↗
PubMed1999

Core-binding factor (CBF) and MLL-associated primary acute myeloid leukemia: biology and clinical implications.

Presence of specific chromosomal abnormalities is one of the most important prognostic factors in acute myeloid leukemia (AML). Recent advances in molecular biology have allowed structural and functional characterization of many of these genomic rearrangements. In many instances, AML is associated with gene fusion, whereby segments from two different genes fuse to give rise to a chimeric structure consisting of the 5' end of one gene and the 3' end of another. Recombinant DNA technology has also permitted the creation of animal models for in vivo studies of the leukemogenic role of several of these chimeric proteins. This review presents current information on the molecular biology and the clinical significance of three of the most common molecular subtypes of AML. In the first two, t(8;21)(q22;q22) and inv(16)(p13q22), disruption of genes encoding for subunits of core-binding factor (CBF), a transcriptional regulator of normal hematopoiesis, occurs, suggesting a common leukemogenic pathway. The third subgroup is characterized by disruption of MLL, a gene that is located at chromosome band 11q23 and encodes a putative transcriptional regulator. This gene is commonly involved in reciprocal translocations of chromosome 11q23 with other gene partners, but, in some instances, MLL disruption occurs by a mechanism of partial tandem duplication, in the absence of any other partner gene. Current data suggest that identification of specific genetic abnormalities in newly diagnosed AML patients is important to predict clinical outcome and, perhaps, to select different therapeutic strategies. The predictive value of detecting these molecular markers to predict cure or relapse in AML patients in complete remission following definitive treatment is still uncertain.

Acute Disease↗