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Biomedical subjects

P R Harris

Publications and source records attributed to P R Harris.

At least 19 recordsLinked to original sources
PubMed2000

Helicobacter pylori-induced mucosal inflammation is Th1 mediated and exacerbated in IL-4, but not IFN-gamma, gene-deficient mice.

To elucidate the pathogenesis of Helicobacter pylori-associated gastritis, we studied immune responses of C57BL/6J wild-type (WT), SCID, and gene deficient (IFN-gamma-/- and IL-4-/-) mice following infection with a pathogenic isolate of H. pylori (SPM326). During early infection in WT mice, mononuclear and polymorphonuclear cells accumulated in the gastric lamina propria, and the numbers of cells in the inflamed mucosa expressing IFN-gamma, but not IL-4, mRNA rose significantly (p < 0.005), consistent with a local Th1 response. Splenic T cells from the same infected WT mice produced high levels of IFN-gamma, no detectable IL-4, and low amounts of IL-10 following in vitro H. pylori urease stimulation, reflecting a systemic Th1 response. Infected C57BL/6J SCID mice did not develop gastric inflammation despite colonization by many bacteria. Infected C57BL/10J and BALB/c mice also did not develop gastric inflammation and displayed a mixed Th1/Th2 splenic cytokine profile. These data imply a major role for the Th1 cytokine IFN-gamma in H. pylori-associated gastric inflammation in C57BL/6J mice. Compared with WT animals, infected IL-4-/- animals had more severe gastritis and higher levels of IFN-gamma production by urease-stimulated splenocytes (p < 0.01), whereas IFN-gamma-/- mice exhibited no gastric inflammation and higher levels of IL-4 production by stimulated splenocytes. These findings establish C57BL/6J mice as an important model for H. pylori infection and demonstrate that up-regulated production of IFN-gamma, in the absence of the opposing effects of IL-4 (and possibly IL-10), plays a pivotal role in promoting H. pylori-induced mucosal inflammation.

Animals↗
PubMed2000

Inflammatory cytokine mRNA expression during early and persistent Helicobacter pylori infection in nonhuman primates.

The role of mononuclear phagocytes in orchestrating the host responses to Helicobacter pylori is inadequately understood. Therefore, gene expression for the monocyte/macrophage-derived cytokines interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha was determined before and during H. pylori infection of rhesus monkeys by use of a highly sensitive quantitative reverse transcriptase polymerase chain reaction. The numbers of molecules of IL-1beta, IL-6, and TNF-alpha mRNA in gastric tissue during early infection (7 weeks) significantly exceeded the preinfection numbers (P<.03). Moreover, the numbers of IL-1beta, IL-6, and TNF-alpha mRNA molecules in persistently infected animals (6 years) also were elevated compared with preinfection numbers (P<.02, P=.03, P=.16, respectively). Cytokine gene expression coincided with progressive H. pylori gastritis, confirmed by increased gastritis scores over preinfection scores (P<.005). These findings provide quantitative evidence that H. pylori induces local gene expression of monocyte/macrophage-derived inflammatory cytokines and evokes an innate response in gastric tissue of nonhuman primates.

Animals↗
PubMed1998

High mucosal levels of tumor necrosis factor alpha messenger RNA in AIDS-associated cytomegalovirus-induced esophagitis.

BACKGROUND & AIMS: To evaluate the role of tumor necrosis factor alpha (TNF-alpha), a key inflammatory cytokine, in cytomegalovirus-associated gastrointestinal disease, we quantitated the level of TNF-alpha messenger RNA (mRNA) in esophageal mucosa from patients with cytomegalovirus-associated esophagitis and acquired immunodeficiency syndrome. METHODS: Four patients underwent endoscopic biopsy of their cytomegalovirus-associated esophageal ulcers before and after ganciclovir therapy. The level of TNF-alpha mRNA in coded esophageal specimens was assessed by in situ hybridization, reverse-transcription polymerase chain reaction, and quantitative polymerase chain reaction. RESULTS: Esophageal mucosa from 3 patients whose ulcers healed or markedly improved contained before therapy numerous macrophages expressing TNF-alpha mRNA and high tissue levels of TNF-alpha mRNA that decreased substantially or were not detectable after therapy. In contrast, esophageal specimens from the single patient whose ulcer worsened after therapy contained many mucosal macrophages expressing TNF-alpha mRNA before as well as after therapy, and the high number of molecules of TNF-alpha mRNA present in the tissue before therapy increased further after treatment. CONCLUSIONS: Increased macrophage production and high tissue levels of TNF-alpha mRNA are associated with cytomegalovirus-associated esophageal ulcers and probably contribute to the inflammatory response associated with cytomegalovirus-induced gastrointestinal disease.

AIDS-Related Opportunistic Infections↗
PubMed1998

Recombinant Helicobacter pylori urease activates primary mucosal macrophages.

Helicobacter pylori urease is absorbed into the gastric mucosa at sites of inflammation, but whether the enzyme activates mucosal macrophages is not known. Because mucosal macrophages differ phenotypically and functionally from blood monocytes, whether recombinant H. pylori urease (rUrease) activated purified lamina propria macrophages in vitro was investigated. rUrease (1-10 microgram/mL) induced primary mucosal macrophages to produce interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha but not IL-8 proteins in a dose-dependent manner (P<.05 to P<.001). Quantitative reverse transcriptase-polymerase chain reaction using capillary electrophoresis laser-induced fluorescence showed that rUrease (0.1-10 microgram/mL) also induced dose-dependent expression of IL-1beta, IL-6, and TNF-alpha but not IL-8 mRNA (P<.05), suggesting that rUrease-induced production of certain cytokines is regulated at the level of gene transcription. These findings indicate that the ability of H. pylori urease to activate mucosal macrophages, resulting in production of proinflammatory cytokines, may be involved in the pathogenesis of H. pylori-associated mucosal inflammation.

Helicobacter pylori↗
PubMed1996

Impact of intestinal lengthening on the nutritional outcome for children with short bowel syndrome.

Survival among children with short bowel syndrome has increased with the use of supportive nutritional techniques including parenteral and enteral nutrition. Further improvement in outcome has been sought by using intestinal lengthening procedures to lengthen the bowel, improve intestinal motility, initiate a progressive increase in intestinal mucosal mass, and thereby improve tolerance to enteral nutrition. The authors examine the growth parameters and the tolerance to enteral nutrition in children with refractory short bowel syndrome before and after intestinal lengthening procedures. For seven children, the percentage of calories from enteral nutrition, the medical and surgical complications, and the number of days in the hospital (1 year before and 2 years after the lengthening procedure) were evaluated. The mean birth weight was 1,991 g (range, 1,198 to 3,096 g). The initial diagnoses requiring bowel resection included necrotizing enterocolitis, multiple small bowel atresias, gastroschisis with midgut volvulus, cloacal exstrophy, and long-segment Hirschsprung's disease. The mean length of the residual small bowel was 49 cm (range, 6 to 92 cm). All but one child had surgical resection of the ileocecal valve. The percentage of enteral nutrition calories significantly increased by 9 months after the procedure (P < .008, analysis of variance). Only one child has been completely weaned from parenteral nutrition. All children's growth parameters have been maintained or improved (weight/age, height/age, and weight/height). Few major medical and surgical complications have been observed. Central venous catheter infection has been the most common medical complication. The mean number of hospitalization days decreased during the second year after the lengthening procedure. The authors conclude that the intestinal lengthening procedure enhances the tolerance for enteral nutrition, improves the nutritional status, and decreases the need for hospitalization. The procedure should be considered for children with refractory short bowel syndrome who require prolonged parenteral nutrition.

Abdominal Muscles↗
PubMed1996

Helicobacter pylori urease is a potent stimulus of mononuclear phagocyte activation and inflammatory cytokine production.

BACKGROUND & AIMS: Helicobacter pylori surface proteins induce the production of proinflammatory mediators by mononuclear phagocytes, but the protein responsible for this stimulation has not been identified. This study determined whether urease, the major component of the soluble proteins extracted from H. pylori grown in culture, activates mononuclear phagocytes and stimulates them to produce proinflammatory cytokines. METHODS: Primary human blood monocytes were incubated with column-purified H. pylori urease and assayed by flow cytometry, Immunoassay, and reverse-transcription polymerase chain reaction for phenotypic, functional, and molecular evidence of activation. RESULTS: H. pylori urease induced monocyte expression of surface interleukin 2 receptors and increased expression of HLA-DR, phenotypic changes consistent with activation. Urease also stimulated dose-dependent production of interleukin 1 beta, interleukin 6, interleukin 8, and tumor necrosis factor alpha peptides and messenger RNA. These urease-induced phenotypic and functional changes were inhibited by preincubation of the urease with antisera to H. pylori whole bacteria, purified urease, or the 31-kilodalton subunit of urease. CONCLUSIONS: Among the soluble proteins released by H. pylori, urease is capable of activating monocytes for proinflammatory cytokines production. The local production of cytokines by urease-stimulated mononuclear phagocytes may play a central role in the development of H. pylori gastroduodenal inflammation.

Base Sequence↗
PubMed1996

Helicobacter pylori cytotoxin induces vacuolation of primary human mucosal epithelial cells.

We investigated whether Helicobacter pylori cytotoxin induces vacuolation in primary epithelial cells from normal human mucosa. Epithelial cells purified by enzyme digestion and elutriation were evaluated for vacuolation in a blinded protocol by light and electron microscopy before and after incubation with culture supernatant (CS) from H. pylori 60190, which has vacuolating activity for HeLa cells (Tox+), and isogenic H. pylori mutant 60190-v1, which lacks this activity (Tox-). Primary epithelial cells (>98% pure) exposed to CS from Tox+ H. pylori exhibited marked vacuolation (52% +/- 5% of cells) compared with epithelial cells exposed to either CS from Tox- H. pylori (23% +/- 3.2%) or uninoculated control broth (23% +/- 3.7%) (P < 0.05) by light microscopy, which was confirmed by electron microscopy and antibody inhibition studies. These are the first data to show that H. pylori cytotoxin causes vacuolation of primary human mucosal epithelial cells.

Bacterial Proteins↗
PubMed1995

The impact of culture on human and space development--new millennial challenge.

The Space Age is causing new applications to the concept of culture, a human coping tool. The exploration and exploitation of outer space resources are altering human culture both on Earth and in orbit. For the first time in history, our species need not merely react and adapt to environment, but plan for a space culture appropriate for extraterrestrial migration. The impact of culture can be analyzed in terms of how space developments alter human perceptions and behavior on this planet; the emergence of a new culture to suit the orbital environment; the organizations that build spacecraft and deploy people aloft; and the technological systems created for spacefaring. This article presents a paradigm for analyzing some of the non-technical human factors involved in space undertakings. It also offers a method for classifying a culture according to ten categories which may be applied both to a macroculture, such as a lunar base; or a microculture, such as a space agency or crew. Human enterprise in space is viewed as both altering the species, and providing a challenge for expanded behavioral and biological scientific research on living and working in space.

Adaptation, Psychological↗
PubMed1991

Nutrition components and assessment procedures of a university employee wellness program: a case study.

This article describes the various nutrition components and data collection tools developed and implemented within the Montana State University Employee Wellness Program. Nutrition components included a variety of classes, seminars, follow-up support groups, and individual consultations. Tools included surveys and computerized data input cards. It is important for dietetic professionals to initiate the development and implementation of a quality nutrition component within university employee wellness programs.

Data Collection↗
PubMed1990

Evaluation tools for undergraduate program planning in times of financial austerity.

This article describes the administration and outcome of two evaluation tools developed by faculty of the dietetic program for ongoing assessment of a Plan IV dietetic education program over a 4-year period. Interns and internship directors were asked to evaluate the level of skills and knowledge base of interns compared with their internship classmates. Interns were also asked to rate the effectiveness of undergraduate course assignments and activities for internship preparation. As a result of the surveys, the home economics core course work was deleted, credits were shifted from food science to nutrient metabolism courses, and credits in clinical nutrition were increased. Projects in clinical nutrition and food systems management were modified. The surveys justified program requirements and utilization of resources, and provided an additional, effective measure of faculty competence.

Curriculum↗
PubMed1989

Behavioral science space contributions.

In anticipation of longer missions on the space stations, Mir and Freedom, as well as a potential return to the Moon and the exploration of Mars, human survival and the quality of life aloft will be increasingly dependent upon research in the behavioral and biological sciences. This article reviews the possible contributions to space habitation of the behavioral sciences--especially anthropology, psychology, and sociology. Before space settlements become a reality, the author makes a case for the broadening of the engineering approach to human factor studies, and consideration of the integrative living systems theory in space planning and management.

Adaptation, Psychological↗
PubMed1989

Human dimensions in space development.

Space exploration is now moving beyond the stage when technical development dominated research. As thinking shifts towards the problems of long-term colonization of the Solar System, the biological and behavioural sciences must make major contributions. This article outlines some of the issues which must be addressed, such as group behaviour and dynamics in space flight, the environment created at space stations and other outposts, recruitment and training of suitable spacefarers, and the planning and governing of space settlements. Ten dimensions of the human aspect of space habitation are described and an indication given of how they may form the basis for a new taxonomy of space planning, operations and management.

Communication↗
PubMed1977

Cervical traction. Review of literature and treatment guidelines.

This article is a review of the literature on cervical traction. The various mechanical factors most relevant to cervical traction are organized and discussed. The factors presented are 1) neck position, 2) traction force, 3) duration of traction, 4) angle of pull, and 5) position of the patient. Treatment guidelines are suggested based on interpretation of the literature.

Biomechanical Phenomena↗
PubMed1974

Coupling between cortical potentials from different areas.

At any instant, the electroencephalogram can be classified as to (i) polarity and (ii) direction of change in polarity. This classification provides a way to measure coupling between cortical areas. The technique is simple, yet of wide potential utility for studying functional relationships between cortical areas. The results of applying this technique suggest how the potentials giving rise to the electroencephalogram may play a role in information processing in the central nervous system.

Cerebral Cortex↗