Guillermo Perez Perez - Academia.edu (original) (raw)

Papers by Guillermo Perez Perez

Acta Neurologica Scandinavica, 2009

Sir In 1996 I published an article “Gastric Helicobacter pylori infection as a cause of idiopathi... more Sir In 1996 I published an article “Gastric Helicobacter pylori infection as a cause of idiopathic Parkinson disease and nonarteritic anterior optic ischemic neuropathy” (l), suggesting a role for H. pylori infection in the pathogenesis of Parkinson’s disease. This paper appeared on all the major databases (e.g. Medline, Current

Scientific Reports

The incidence of kidney stones is increasing in the US population. Oxalate, a major factor for st... more The incidence of kidney stones is increasing in the US population. Oxalate, a major factor for stone formation, is degraded by gut bacteria reducing its intestinal absorption. Intestinal O. formigenes colonization has been associated with a lower risk for recurrent kidney stones in humans. In the current study, we used a clinical trial of the eradication of Helicobacter pylori to assess the effects of an antibiotic course on O. formigenes colonization, urine electrolytes, and the composition of the intestinal microbiome. Of 69 healthy adult subjects recruited, 19 received antibiotics for H. pylori eradication, while 46 were followed as controls. Serial fecal samples were examined for O. formigenes presence and microbiota characteristics. Urine, collected serially fasting and following a standard meal, was tested for oxalate and electrolyte concentrations. O. formigenes prevalence was 50%. Colonization was significantly and persistently suppressed in antibiotic-exposed subjects but r...

Genome Medicine, 2020

Background There is increasing evidence that the intestinal microbiota plays a crucial role in th... more Background There is increasing evidence that the intestinal microbiota plays a crucial role in the maturation of the immune system and the prevention of diseases during childhood. Early-life short-course antibiotic use may affect the progression of subsequent disease conditions by changing both host microbiota and immunologic development. Epidemiologic studies provide evidence that early-life antibiotic exposures predispose to inflammatory bowel disease (IBD). Methods By using a murine model of dextran sodium sulfate (DSS)-induced colitis, we evaluated the effect on disease outcomes of early-life pulsed antibiotic treatment (PAT) using tylosin, a macrolide and amoxicillin, a beta-lactam. We evaluated microbiota effects at the 16S rRNA gene level, and intestinal T cells by flow cytometry. Antibiotic-perturbed or control microbiota were transferred to pups that then were challenged with DSS. Results A single PAT course early-in-life exacerbated later DSS-induced colitis by both pertur...

Infection and Immunity, 1997

Helicobacter pylori persistently colonizes the human gastrointestinal tract and is associated wit... more Helicobacter pylori persistently colonizes the human gastrointestinal tract and is associated with chronic gastritis and, in some cases, peptic ulcer disease or gastric neoplasms. One factor in the persistence of this organism may be its inability to elicit a strong inflammatory response. Lipopolysaccharide (LPS) is a proinflammatory substance found in the cell walls of all gram-negative bacteria. H. pylori LPS has been found by several different measures to be less active than LPS from Enterobacteriaceae. This study addresses the role of CD14 and LPS-binding protein in the cellular response to H. pylori LPS. We report that H. pylori LPS activates mammalian cells expressing CD14 at much lower LPS concentrations than those for control cells not expressing CD14. The maximal activation of CD14-70Z/3 cells by H. pylori LPS also requires LPS-binding protein. H. pylori LPS at concentrations as high as 30 microg/ml does not elicit an interleukin-8 (IL-8) response from the epithelial cell l...

Nature Microbiology, 2016

Together with plague, smallpox and typhus, epidemics of dysentery have been a major scourge of hu... more Together with plague, smallpox and typhus, epidemics of dysentery have been a major scourge of human populations for centuries 1. A previous genomic study concluded that Shigella dysenteriae type 1 (Sd1), the epidemic dysentery bacillus, emerged and spread worldwide after World War (WW) I, with no clear pattern of transmission 2. This is not consistent with the massive cyclic dysentery epidemics reported in Europe during the 18th and 19th centuries 1,3,4 and the first isolation of Sd1 in Japan in 1897 5. We report here a whole-genome analysis of 331 Sd1 isolates from around the world, collected between 1915 and 2011, providing us with unprecedented insight into the historical spread of this pathogen. We show here that Sd1 has existed since at least the 18th century, and that it swept the globe at the end of the 19th century, diversifying into distinct lineages associated with WWI, WWII, and various conflicts or natural disasters across Africa, Asia, and Central America. We also provide a unique historical perspective on the evolution of antibiotic resistance over a 100-year period, beginning decades before the antibiotic era, and identify a prevalent multiple antibiotic-resistant lineage in South Asia that was transmitted in several waves to Africa, where it caused severe outbreaks of disease.

Veterinary Microbiology, 2011

The mammalian gastric and oral mucosa may be colonized by mixed Helicobacter and Campylobacter sp... more The mammalian gastric and oral mucosa may be colonized by mixed Helicobacter and Campylobacter species, respectively, in individual animals. To better characterize the presence and distribution of Helicobacter and Campylobacter among marine mammals, we used PCR and 16S rDNA sequence analysis to examine gastric and oral samples from ten dolphins (Tursiops gephyreus), one killer whale (Orcinus orca), one false killer whale (Pseudorca crassidens), and three wild La Plata river dolphins (Pontoporia blainvillei). Helicobacter spp. DNA was widely distributed in gastric and oral samples from both captive and wild cetaceans. Phylogenetic analysis demonstrated two Helicobacter sequence clusters, one closely related to H. cetorum, a species isolated from dolphins and whales in North America. The second related cluster was to sequences obtained from dolphins in Australia and to gastric non-Helicobacter pylori helicobacters, and may represent a novel taxonomic group. Dental plaque sequences from four dolphins formed a third cluster within the Campylobacter genus that likely represents a novel species isolated from marine mammals. Identification of identical Helicobacter spp. DNA sequences from dental plaque, saliva and gastric fluids from the same hosts, suggests that the oral cavity may be involved in transmission. These results demonstrate that Helicobacter and Campylobacter species are

Proceedings of the National Academy of Sciences, 2002

Phylogenies of indigenous microbes have been used as surrogates for the origins of the hosts that... more Phylogenies of indigenous microbes have been used as surrogates for the origins of the hosts that carry them. Conversely, polymorphisms may be used to date the spread of a microbial species when information about their host populations is available. Therefore, we examined polymorphisms in Helicobacter pylori , which persistently colonize the human stomach, to test the hypothesis that they have been ancient inhabitants of humans. Three H. pylori loci that previously have been shown to have phylogeographic affinity have been analyzed for two populations with different ethnic origins from Venezuela. In a group of Amerindian subjects from Amazonia, East Asian H. pylori genotypes were present for each of the loci examined but were absent in a mestizo population from Caracas. These findings provide evidence that H. pylori has been present in humans at least since ancestors of Amerindians migrated from Asia more than 11,000 years ago.

Obesity Surgery, 2008

Background-We hypothesized that laparoscopic adjustable gastric banding (LAGB) reduces weight and... more Background-We hypothesized that laparoscopic adjustable gastric banding (LAGB) reduces weight and modulates ghrelin production, but largely spares gastrointestinal endocrine function.

Journal of Clinical Microbiology, 2002

We demonstrate that Bacillus anthracis may be detected from a formalin-fixed, paraffin-embedded b... more We demonstrate that Bacillus anthracis may be detected from a formalin-fixed, paraffin-embedded biopsy specimen, even after the patient has received antibiotic treatment. Although traditional PCR methods may not be sufficiently sensitive for anthrax detection in such patients, cycle numbers can be increased or PCR can be repeated by using an aliquot from a previous PCR as the template.

Journal of Clinical Microbiology, 2010

Helicobacter pylori is known to be a major cause of gastric carcinoma and peptic ulceration. cagA... more Helicobacter pylori is known to be a major cause of gastric carcinoma and peptic ulceration. cagA positivity and vacA 's signal regions and mid-regions are well-characterized markers of H. pylori 's virulence. Recently, an intermediate region has been identified as another strong marker of H. pylori -associated disease, and its i1 allele has been linked with severe diseases in colonized hosts. The goal of this study was to determine the prevalence of the intermediate alleles in H. pylori isolates from China, Turkey, and Uruguay and from U.S. Africans and to compare their distribution with other well-characterized virulence factors. Originally, 123 H. pylori strains were studied, but 3 were excluded due to the failure to amplify the intermediate region in these samples. Therefore, a total of 120 strains were analyzed: 30 Chinese isolates, 35 Turkish isolates, 30 Uruguayan isolates, and 25 U.S. African isolates. The s type and the m type were determined by PCR amplification. T...

Emerging Infectious Diseases, 2004

Emerging Infectious Diseases, 2006

Critical Care Medicine, 1996

Background/purpose: We aimed to identify the risk factors of first-time occurrence of nonvariceal... more Background/purpose: We aimed to identify the risk factors of first-time occurrence of nonvariceal upper gastrointestinal bleeding (UGIB) among aspirin users after adjusting for confounding factors like age, gender, underlying co-morbidities, and medications. Methods: Using the National Health Insurance Research Database of Taiwan and matching age, gender, underlying co-morbidities and enrollment time by propensity score, 11105 aspirin users and 11105 controls were identified for comparison from a cohort dataset of 1,000,000 randomly sampled subjects. Cox proportional hazard regression models were used to identify independent risk factors for first-time occurrence of non-variceal UGIB in the study cohort and in the aspirin users after adjusting for age, gender, underlying comorbidities, and medications (e.g., non-steroidal anti-inflammatory drugs [NSAIDs], cyclooxygenase-2 [COX-2] inhibitors, steroids, thienopyridines, selective serotonin reuptake inhibitors, warfarin, and dipyridamole). Results: By Cox proportional hazard regression analysis, aspirin use increased the risk of first-time occurrence of UGIB (hazard ratio [HR]: 1.48; 95% confidence interval [CI]: 1.28e1.72). Age, male

The American Journal of Pathology, 2011

The host immune response directed against Helicobacter pylori is ineffective in eliminating the o... more The host immune response directed against Helicobacter pylori is ineffective in eliminating the organism and strains harboring the cag pathogenicity island augment disease risk. Because eosinophils are a prominent component of H. pylori-induced gastritis, we investigated microbial and host mechanisms through which H. pylori regulates eosinophil migration. Our results indicate that H. pylori increases production of the chemokines CCL2, CCL5, and granulocyte-macrophage colony-stimulating factor by gastric epithelial cells and that these molecules induce eosinophil migration. These events are mediated by the cag pathogenicity island and by mitogen-activated protein kinases, suggesting that eosinophil migration orchestrated by H. pylori is regulated by a virulence-related locus.

The ISME Journal, 2020

Helicobacter pyloriis a common component of the human stomach microbiota, possibly dating back to... more Helicobacter pyloriis a common component of the human stomach microbiota, possibly dating back to the speciation ofHomo sapiens. A history of pathogen evolution in allopatry has led to the development of genetically distinctH. pylorisubpopulations, associated with different human populations, and more recent admixture amongH. pylorisubpopulations can provide information about human migrations. However, little is known about the degree to which someH. pylorigenes are conserved in the face of admixture, potentially indicating host adaptation, or how virulence genes spread among different populations. We analyzedH. pylorigenomes from 14 countries in the Americas, strains from the Iberian Peninsula, and public genomes from Europe, Africa, and Asia, to investigate how admixture varies across different regions and gene families. Whole-genome analyses of 723H. pyloristrains from around the world showed evidence of frequent admixture in the American strains with a complex mosaic of contribu...

Journal of Clinical Microbiology, 1995

Approximately 60% of Helicobacter pylori isolates possess the cagA gene and express its 120- to 1... more Approximately 60% of Helicobacter pylori isolates possess the cagA gene and express its 120- to 140-kDa product (CagA). In this study, the cagA gene was detected in H. pylori isolates from 26 (81.3%) of 32 patients with duodenal ulcers (DU), 17 (68.0%) of 25 patients with gastric ulcers, and 23 (59.0%) of 39 patients with nonulcer dyspepsia (NUD). By Western blotting (immunoblotting) with antiserum to CagA, in vitro CagA expression was demonstrated for 95.5% of cagA+ strains compared with 0% of strains lacking cagA. Sera from patients infected with cagA+ strains (n = 66) reacted with recombinant CagA in an enzyme-linked immunosorbent assay to a significantly greater extent than either sera from patients infected with strains lacking cagA (n = 30) or sera from uninfected persons (n = 25) (P < 0.001). A strain lacking cagA was isolated from eight patients who had serum immunoglobulin G antibodies to CagA, which suggests that these patients were infected with multiple strains. Serum...

Clinical and diagnostic laboratory immunology, 1997

For Helicobacter pylori, the hsp60 heat shock protein encoded by hspB is being considered as a po... more For Helicobacter pylori, the hsp60 heat shock protein encoded by hspB is being considered as a potential candidate for subunit vaccines. We investigated the humoral and cellular responses to H. pylori hsp60 and its cross-reactivity with the homologous Mycobacterium bovis p65 protein and autologous human hsp60 protein. H. pylori-infected persons had significantly higher levels than uninfected persons of serum immunoglobulin G antibodies recognizing H. pylori hsp60, but not M. bovis p65 or human hsp60, as determined by enzyme-linked immunosorbent assay. In contrast, immunoblotting demonstrated cross-reactivity of H. pylori hsp60 with human hsp60. T-cell recognition of H. pylori hsp60 was found in both infected and uninfected subjects, and there was no recognition of human hsp60. T cells from infected and uninfected subjects that had been activated in response to H. pylori hsp60 or M. bovis p65 were phenotypically similar but appeared to secrete different levels of gamma interferon and...

Clinical and Diagnostic Laboratory Immunology, 1999

Several different families of vacuolating toxin (vacA) alleles are present in Helicobacter pylori... more Several different families of vacuolating toxin (vacA) alleles are present in Helicobacter pylori, and they encode products with differing functional activities. H. pyloristrains containing certain types of vacA alleles have been associated with an increased risk for peptic ulcer disease. In this study, we tested serum samples and gastric juice from 19 H. pylori-negative and 39 H. pylori-positive patients for enzyme-linked immunosorbent assay reactivity with two different types of VacA antigens (types s1/m1 and s2/m2), which were purified from H. pylori 60190 and 86-338, respectively. Both antigens were recognized better by serum immunoglobulin G (IgG) fromH. pylori-positive persons than by serum IgG from H. pylori-negative persons (P < 0.01). The s1/m1 VacA antigen was better recognized by sera from patients carryingvacA type s1/m1 strains than by sera from patients carryingvacA type s2/m2 or s1/m2 strains (P < 0.01). Conversely, the s2/m2 VacA antigen was better recognized b...

VoI ý1. No I W) 19-9567i86!070(,47-06St)2. ft)

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2002

Incidence and mortality rates for gastric cancer in rural People's Republic of China differ g... more Incidence and mortality rates for gastric cancer in rural People's Republic of China differ greatly over short distances. In Shandong Province, we studied asymptomatic adult subjects from Bei Duan village (n = 196) in Linqu County (a high-risk area for gastric cancer) and from Shi Huang village (n = 192) in Cangshan County (a low-risk area for gastric cancer). The prevalence of advanced precancerous gastric lesions (APGL) was assessed by microscopic examination of endoscopic stomach biopsies. ELISAs were used to detect serum IgG to Helicobacter pylori whole-cell antigen and to the CagA protein. A logistic regression model was used to quantify the role of the two H. pylori seromarkers in explaining the differences in prevalence of APGL between the two villages after adjusting for age and sex. The prevalence of APGL was much greater in Bei Duan than in Shi Huang. Although H. pylori seroprevalence by the whole-cell ELISA was similar in the two populations, seroprevalence of CagA wa...