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At least 577 records · Page 32Linked to original sources

Development of malabsorption and nutritional complications in simian immunodeficiency virus-infected rhesus macaques.

OBJECTIVE: To assess the development and cause of malabsorption in rhesus macaques following experimental simian immunodeficiency virus (SIV) infection and to evaluate its impact on nutritional status. DESIGN: Clinical malabsorption tests and serial jejunal aspirates and biopsies were obtained from nine SIV-infected and three uninfected animals prior to infection and at 1, 2, 4, 8, 12, 24, 40 and 52 weeks postinoculation. METHODS: Malabsorption was measured by sucrose breath hydrogen (H2) analysis and blood assay of D-xylose. Digestive enzyme activity was determined in jejunal mucosal homogenates. Bacterial and protozoal flora were determined in jejunal aspirates. Nutritional assessment was evaluated using specific blood micronutrient values. Cellular targets of SIV in the jejunum were determined by combined in situ hybridization and immunohistochemistry. RESULTS: Eight out of nine SIV-infected monkeys, including asymptomatic animals, exhibited malabsorption by either increased breath H2 and/or decreased blood D-xylose. All animals that died of AIDS had diarrhea, D-xylose malabsorption and decreased sucrase activity. Significant changes in nutritional status were associated with malabsorption. Bacterial overgrowth was not considered to be a cause of malabsorption. Histopathological biopsy findings included dilated villus lacteals, excessive cellular debris, lymphoplasmocytic infiltrates and cytoplasmic vacuoles in crypt epithelial cells. SIV-infected T cells and macrophages were detected as early as 1 week postinoculation. CONCLUSIONS: SIV-associated malabsorption can occur prior to clinical complications of disease. Severe intestinal complications are associated with malabsorption and malnutrition in the terminal stages of AIDS. The high proportion of macaques experiencing malabsorption without detectable pathogens, suggests an enteropathogenic role for SIV.

Animals↗

Uncertain clinical significance of duodenal mucosal abnormalities in HIV-infected individuals. Results of a case-control study.

Previous research has described abnormalities of duodenal mucosal morphology in human immunodeficiency virus (HIV)-infected individuals. We wanted to determine the frequency of disturbed villus architecture and investigate its relationship to HIV-related chronic diarrhea. We conducted a case-control study of 120 HIV-infected men, 63 with and 57 without chronic diarrhea. Stools were cultured for bacteria and examined for ova and parasites; esophagogastroduodenoscopy and flexible sigmoidoscopy with mucosal biopsies were performed. Biopsy tissue was examined using light and electron microscopy to detect enteric pathogens and to evaluate mucosal morphology. The mean CD4+ cell count was 143/min3, and enteric pathogens were detected in 56 of 120 men (47%). In approximately half the study sample (57%), duodenal villus architecture was normal; complete villus flattening was not observed. We detected no association between chronic diarrhea and altered villus architecture. Although further study is needed to clarify the pathogenesis of altered duodenal mucosal morphology, our results suggest that the clinical significance of the abnormalities may be small.

Adult↗

Human herpesvirus-6 meningoencephalitis in a recipient of an unrelated allogeneic bone marrow transplantation.

BACKGROUND: Human herpesvirus-6 (HHV-6) has been implicated in bone marrow suppression, interstitial pneumonitis, and fatal meningoencephalitis in bone marrow transplant (BMT) recipients. METHODS: We describe the case of a woman with acute myeloid leukemia in second remission who developed febrile meningoencephalitis 8 months after a second unrelated BMT. RESULTS: Computed tomography and magnetic resonance images of the brain were nonspecific. Analysis of cerebrospinal fluid (CSF) revealed lymphocytosis and an increased protein level. Using polymerase chain reaction methods, HHV-6 was the only pathogen detected in CSF, peripheral blood mononuclear cells, and bone marrow. The patient was treated with ganciclovir and foscarnet for 3 months. All clinical manifestations resolved and HHV-6 polymerase chain reaction analysis of CSF became negative 40 days after the beginning of antiviral treatment. CONCLUSIONS: This observation strongly suggests that HHV-6 should be sought in BMT patients with neurological complications and that HHV-6 meningoencephalitis may respond to ganciclovir and foscarnet therapy.

Acute Disease↗

Fatal primary infection due to human herpesvirus 6 variant A in a renal transplant recipient.

We describe a fatal primary human herpesvirus 6 (HHV-6) variant A infection in a kidney transplanted adult woman. On day 20 post transplantation (TX), after rejection therapy, the patient presented an acute hemophagocytic syndrome with hepatitis and central nervous system involvement. HHV-6 IgG and IgM antibodies seroconversion was demonstrated. HHV-6 variant A was the sole pathogen detected by nested PCR and/or culture in blood, bone marrow aspiration, liver biopsy, cerebrospinal fluid and bronchoalveolar lavage. The graft was HHV-6 seropositive and the patient was not transfused before day 28 post TX, suggesting that the virus was transmitted by the graft. Despite immunoglobulins, ganciclovir and foscarnet therapy, the HHV-6 infection progressed and led to severe aplasia. The patient developed Aspergillus fumigatus pneumonia and died from fulminant candidemia. This case demonstrated for the first time that HHV-6 variant A primary infection can cause life-threatening disseminated infection in immunosuppressed patients.

Adult↗

Severe pancytopenia and hemophagocytosis after HHV-8 primary infection in a renal transplant patient successfully treated with foscarnet.

We report the occurrence of human herpesvirus (HHV)-8 primary infection in an adult male kidney recipient. Four months after transplantation, the patient developed visceral Kaposi sarcoma, and 1 month later he presented with progressive and severe peripheral cytopenia, in the presence of a normocellular or hypercellular bone marrow (BM) with hemophagocytosis. HHV-8 was the sole pathogen detected by polymerase chain reaction either in the serum or in the BM. HHV-8 latent nuclear antigen was detected in immature progenitor cells from the BM. Immunosuppressive therapy was reduced, and the patient was treated with foscarnet for 2 weeks, leading to a dramatic normalization of blood cell counts, concomitantly with the disappearance of HHV-8 viremia. At the end of antiviral therapy, the patient received chemotherapy, and Kaposi sarcoma regressed in 2 months. Severe peripheral cytopenia may be a posttransplant complication after HHV-8 infection, for which treatment with foscarnet seems appropriate.

Antiviral Agents↗

Poliomyelitis-like syndrome in a child with West Nile virus infection.

West Nile virus (WNV) infections of the central nervous system are very uncommon in U.S. children. We report a child with a poliomyelitis-like presentation in which WNV was the only detected pathogen. WNV has not previously been associated with a poliomyelitis-like presentation in children.

Child↗

Assessment of the pathogenic potential of two Listeria monocytogenes human faecal carriage isolates.

Two human faeces carriage isolates of Listeria monocytogenes (H1 and H2) were compared to reference strains (ScottA and LO28) with regard to their lethality in 14-day-old chick embryos, their haemolytic and phospholipase (phosphatidylcholine-phospholipase C and phosphatidylinositol-phospholipase C) activities and their invasiveness towards Caco-2 cells. Experimental infection of chick embryos allowed discrimination of the strains into those exhibiting high virulence (ScottA and H2), those exhibiting slightly attenuated virulence (LO28) and those exhibiting low virulence (H1). A similar percentage mortality and time to death for embryos was observed when they were infected with H2 as was seen with infection by the reference strain ScottA. Therefore, human carriage strain H2 was considered potentially pathogenic. In contrast to H2 and ScottA, H1 exhibited low virulence. Using the tissue-culture cell-line model, it was found that carriage strain H1 was unable to enter Caco-2 cells efficiently, even though it was similar to the virulent strains in terms of the enzymic activities involved in pathogenicity. Detection of the internalins InlA and InlB, involved in the internalization of L. monocytogenes in the host cells, by immunoblot indicated that a truncated form of InlA was produced by H1. Taken together, these data provide a starting point for the study of the behaviour of two types of human faeces carriage strains and their characterization.

Animals↗

Dendritic cells, DRiPs, and DALIS in the control of antigen processing.

The study of the cell biology of antigen processing and presentation has greatly contributed to our understanding of the immune response. The work of many immunologically inclined cell biologists has also permitted new insights into cellular mechanisms shared by many cell types. Here are described recent and particularly exciting findings on the regulation of major histocompatibility complex class I-restricted presentation in dendritic cells and their contribution to the deciphering of the cellular response to pathogen detection.

Animals↗

The relationship between concentration of a dual marker strain of Salmonella Typhimurium in bovine faeces and its probability of detection by immunomagnetic separation and culture.

AIMS: To modify a strain of Salmonella serotype Typhimurium to express unique marker traits and then define how the concentration of the marker in bovine faeces affects the probability of its detection by culture preceded by immunomagnetic separation (IMS). METHODS AND RESULTS: DNA encoding for the production of green fluorescent protein (gfp) and resistance to kanamycin was inserted into the bacterial chromosome of Salm. Typhimurium. Transposon insertion was demonstrated by Southern blot hybridization. Varying amounts of one electroporant (gfpSal-1) were inoculated into suspensions of bovine faeces and attempts made to isolate gfpSal-1 using a protocol based on pre-enrichment incubation, IMS and enrichment in selective media. Isolates of gfpSal-1 were differentiated from wild strains of Salmonella using fluorescence under u.v. light and expression of kanamycin resistance. A logistic and Gompertz function each derived from the dose-response data partially explained the observations with the fit of the Gompertz function judged to be superior. The 10, 50 and 90% limits of detection from the Gompertz function were estimated to be 1.92, 2.03 and 2.27 CFU g(-1) respectively. CONCLUSIONS: Reliance on the traditional concept of 'limit of detection' could introduce unacceptable errors in the interpretation of test findings when the concentration of Salm. Typhimurium in bovine faeces (pooled or individual) is below ca 3 CFU g(-1) of faeces. SIGNIFICANCE AND IMPACT OF THE STUDY: The dose-response curve can be used to aid the design of protocols for detecting Salmonella in individual and pooled faecal specimens. The experiments demonstrate that both reporter genes in tandem are useful for studying the performance of culture-based methods for detecting pathogens in faeces.

Animals↗

Role of MAP kinase-dependent apoptotic pathway in innate immune responses and viral infection.

Mitogen-activated protein (MAP) kinase cascades are multifunctional signalling networks that influence cell growth, differentiation, apoptosis and cellular responses to stress. Apoptosis signal-regulating kinase 1 (ASK1) is a MAP kinase kinase kinase that triggers apoptogenic kinase cascade leading to the phosphorylation/activation of c-Jun N-terminal kinases (JNK) and p38-MAP kinase, which are responsible to induce apoptotic cell death. This pathway plays a pivotal role in the transduction of signals from different apoptotic stimuli. Recently, it has become evident that ASK1 and its downstream pathway are employed in the transduction of signals from Toll-like receptors (TLR) - multistep processes that interfere with different intracellular signalling pathways. TLR are the key proteins that allow mammals to detect pathogens and mediate innate immune responses. In addition, ASK1 and its downstream pathway play a target role in the regulation of apoptosis in some cases of viral infection - AIDS, influenza, hepatitis C and others. In the present review, we summarize current knowledge about the role of ASK1 and its downstream pathway in innate immune responses and viral infection.

Animals↗

Lymphoid organ dendritic cells: beyond the Langerhans cells paradigm.

The immune system has developed mechanisms to detect and initiate responses to a continual barrage of immunological challenges. Dendritic cells (DC), a heterogeneous population of leucocytes, play a major role as immunosurveillance agents. To accomplish this function, DC are equipped with highly efficient mechanisms to detect pathogens, to capture, process and present antigens, and to initiate T-cell responses. These mechanisms are developmentally regulated during the DC life cycle in a process termed 'maturation', which was originally defined using Langerhans cells (LC), a DC type of the epidermis. LC exist in the skin in an immature state dedicated to capturing antigens, and in the subcutaneous lymph nodes in a mature state dedicated to presenting those antigens to T cells. The phenotypic changes undergone by LC during maturation, and the correlation of these changes with tissue localization, have been generally considered a paradigm for all DC. However, studies of the multiple DC types found in the lymphoid organs of mice and humans have revealed that most DC subsets do not follow the life cycle typified by LC. In this review we discuss the limitations of the 'LC paradigm' and suggest that this model should be revised to accommodate the heterogeneity of the DC system. We also discuss the implications of the maturational status of the DC subsets contained in the lymphoid organs for their putative roles in the induction of immune responses and the maintenance of peripheral tolerance.

Animals↗

Mutational analysis of the estrogen receptor-alpha gene in familial ovarian cancer.

AIM: The genetic region of 6q25 containing the estrogen receptor-alpha (ER-alpha) gene is lost in a significant number of ovarian tumors. The aim of this study was to identify how inherited variation in the ER-alpha gene contributes to susceptibility to familial ovarian cancer. METHODS: DNA obtained from 18 cases of familial ovarian cancer without mutation of the BRCA1 and BRCA2 genes, 20 cases with BRCA1 mutation, 20 cases of sporadic ovarian cancer, and 19 controls were screened for mutations in the coding region of the ER-alpha gene using direct sequencing. RESULTS: Two germline missense variants at codons 307 [GCC(Ala)-->TCC(Ser)] and 347 [ACC(Thr)-->TCC(Ser)] were detected in two unrelated cases with BRCA1 mutation, but not in all other cases tested. Three polymorphisms in codon 10 [TCT-->TCC(Ser)], codon 325 [CCC-->CCG(Pro)], and codon 594 [ACA-->ACG(Thr)] were identified in this series, and a higher frequency of the allele TCC at codon 10 and a lower frequency of the allele CCG at codon 325 were observed in familial cases without BRCA1 mutation, compared with those in familial cases with BRCA1 mutation, in both the sporadic cases and in the controls. CONCLUSIONS: We could not detect pathogenic mutations of the ER-alpha gene in ovarian cancer cases without BRCA1 mutation. However, association analyses of two polymorphisms suggest that the ER-alpha gene or a gene located close to the ER-alpha locus might be related to susceptibility of familial ovarian cancer without BRCA1 mutation.

Adult↗

How to kill a mocking bug?

All metazoans have evolved means to protect themselves from threats present in the environment: injuries, viruses, fungi, bacteria and other parasites. Insect protection includes innate physical barriers and both cellular and humoral responses. The insect innate immune response, best characterized in Drosophila melanogaster, is a rapid broad response, triggered by pathogen-associated molecular patterns (PAMPs) recognition, which produces a limited range of effectors that does not alter upon continued pathogen exposure and lacks immunological memory. The Drosophila response, particularly its humoral response, has been investigated by both low and high-throughput methods. Three signalling pathways conserved between insects and mammals have been implicated in this response: Toll (equivalent to mammalian TLR), Imd (equivalent to TNFalpha) and Hop (equivalent to JAK/STAT). This review provides an entry point to the insect immune system literature outlining the main themes in D. melanogaster bacterial pathogen detection and humoral and cellular immune responses. The Drosophila immune response is compared with other insects and the mammalian immune system.

Animals↗

Epidemiologic Observations on Diarrhea Developing in U.S. and Mexican Students Living in Guadalajara, Mexico.

Background: A previous study suggested that U.S. students who lived in Mexico for 1 year had a risk of diarrhea intermediate between the rate for newly arrived U.S. students and Mexican students; however, the study was not controlled for changes of risky behavior over time. Methods: An analysis of acute diarrhea occurring among U.S. and Mexican student groups living in Guadalajara, Mexico was conducted to explore the association of diarrhea developing during selected 28-day periods with length of residence, season, and risk factors such as locations of food consumption, consumption of tap water, unsafe ice, alcohol, and antibiotics. Results: Compared to U.S. and Mexican student groups, newly arrived U.S. college students in July had the highest rate of diarrhea (55%), highest enteropathogen isolation rate (46%), and most consumption of alcohol and antibiotics; they also ate most frequently at restaurants and in Mexican family homes. Compared to a 34% rate of diarrhea among newly arrived U.S. medical students in August, the rate was only 6% among established medical students in January. This drop in attack rate was attended by less tap water and unsafe ice consumption by established students in January compared to the habits of newly arrived students in January or August when risky behavior was otherwise similar among these groups. The role of tap water and unsafe ice in the acquisition of wintertime diarrhea is further supported by the relatively high 29% rate of diarrhea among U.S. medical students newly arrived in January, who also consumed more tap water and ice than established students in January. Enterotoxigenic E. coli disease was observed only during the summer months; whereas, Campylobacter jejuni disease and disease associated with no detected pathogen were more common in winter. Conclusions: These data imply that wintertime diarrhea in Guadalajara is more likely than summertime diarrhea to be waterborne and to be caused by agents such as viruses or previously unrecognized enteropathogens that were not assessed in this study. Among Mexican students who had the highest frequency of tap water consumption and eating from vendors, the low rates of diarrhea in summer (3%) and winter (5%) imply that they enjoy a substantial degree of immunity. Further study will be necessary to understand the role that immunity (or its loss during summer vacation back in the United States) might play in additionally accounting for observed differences in attack rates between newly arrived students and those who had lived for a period of time in Mexico. (J Travel Med 2:6-10, 1995)

Journal Article↗

Rapid, automated nucleic acid probe assays using silicon microstructures for nucleic acid concentration.

A system for rapid point-of-use nucleic acid (NA) analysis based on PCR techniques is described. The extraction and concentration of DNA from test samples has been accomplished utilizing silicon fluidic microchips with high surface-area-to-volume ratios. Short (500 bp) and medium size (48,000 bp) DNA have been captured, washed, and eluted using the silicon dioxide surfaces of these chips. Chaotropic (GuHCl) salt solutions were used as binding agents. Wash and elution agents consisted of ethanol-based solutions and water, respectively. DNA quantities approaching 40 ng/cm2 of binding area were captured from input solutions in the 100-1000 ng/mL concentration range. For dilute samples of interest for pathogen detection, PCR and gel electrophoresis were used to demonstrate extraction efficiencies of about 50 percent, and concentration factors of about 10x using bacteriophage lambda DNA as the target. Rapid, multichannel PCR thermal cycling modules with integrated solid-state detection components have also been demonstrated. These results confirm the viability of utilizing these components as elements of a compact, disposable cartridge system for the detection of NA in applications such as clinical diagnostics, biowarfare agent detection, food quality control, and environmental monitoring.

Automation↗

[An epidemiological investigation for gram-positive coccus, especially MRSA, in Kinki area].

An epidemiological investigation for Methicillin-resistant Staphylococcus aureus (MRSA) was performed at 21 medical institutes in Kinki area by the questionnaire from Kinki Infection Working Group in 1995. The most frequent specimen for MRSA was pus (25.3%) from out-patients and sputum (34.4%) from in-patients, respectively. As compared to the investigation of the MRSA Forum in 1992 and 1993, MRSA increased over 20%, and furthermore 57.8% was MRSA out of S. aureus under this study. It demonstrated that drug-resistance was accelerated for a few years. Polymicrobial infection, especially with more than 3 pathogens, increased significantly compared with the results of the MRSA Forum (p < 0.01). It was suggested that compromized host increased and therapy turned to be more difficult. Simultaneous pathogens detected with MRSA were Candida species, Pseudomonas aeruginosa and Enterococcus faecalis. In terms of chemosusceptibility, VCM (99.9%), ST (99.4%) and ABK (99.3%) were still determined to be highly sensitivity against MRSA.

Drug Resistance, Microbial↗

[Clinical study of 28 children with bacterial meningitis].

A retrospective study was conducted on 28 patients with bacterial meningitis who were admitted to our department between April 1988 and March 2002. The most commonly detected pathogen was group B Streptococcus in those under 1 month of age and Haemophilus influenzae (72.2%) among those over 1 month. The most commonly administered antibiotic combination (67.9%) at the initial treatment was that of cefotaxime (CTX) and ampicillin (ABPC). We encountered one case that was resistant to both CTX and ABPC. Through this experience, it became apparent that for the initial treatment of bacterial meningitis in infants, it is necessary to apply a combination of two antibiotics, instead of a single agent, and new antibiotics should be considered for such combinations rather than persisting on conventional CTX and ABPC. The aforementioned 28 patients were divided into 2 groups--7 patients (25.0%) with sequelae and 21 (75.0%) without--and various factors noted during the diagnosis were evaluated retrospectively. It was found that the number of days leading to admission at the hospital and the development of convulsions were unrelated to the prognosis. Those who succumbed or suffered sequelae were all infants under 1 year of age. All cases were caused by genus Haemophilus.

Ampicillin↗

T cell activation by lipopeptide antigens.

Unlike major histocompatibility proteins, which bind peptides, CD1 proteins display lipid antigens to T cells. Here, we report that CD1a presents a family of previously unknown lipopeptides from Mycobacterium tuberculosis, named didehydroxymycobactins because of their structural relation to mycobactin siderophores. T cell activation was mediated by the alphabeta T cell receptors and was specific for structure of the acyl and peptidic components of these antigens. These studies identify a means of intracellular pathogen detection and identify lipopeptides as a biochemical class of antigens for T cells, which, like conventional peptides, have a potential for marked structural diversity.

Antigen Presentation↗