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Biomedical subjects

M J Roy

Publications and source records attributed to M J Roy.

At least 19 recordsLinked to original sources
PubMed2000

Induction of antigen-specific CD8+ T cells, T helper cells, and protective levels of antibody in humans by particle-mediated administration of a hepatitis B virus DNA vaccine.

A DNA vaccine against the hepatitis B virus (HBV) was evaluated for safety and induction of immune responses in 12 healthy, hepatitis-naïve human volunteers using the needle-free PowderJect system to deliver gold particles coated with DNA directly into cells of the skin. Three groups of four volunteers received three administrations of DNA encoding the surface antigen of HBV at one of the three dose levels (1, 2, or 4 microg). The vaccine was safe and well tolerated, causing only transient and mild to moderate responses at the site of administration. HBV-specific antibody and both CD4+ and CD8+ T cell responses were measured before and after each immunization. All the volunteers developed protective antibody responses of at least 10 mIU/ml. In volunteers who were positive for the HLA class I A2 allele, the vaccine also induced antigen-specific CD8+ T cells that bound HLA-A2/HBsAg(335-343) tetramers, secreted IFN-gamma, and lysed target cells presenting a hepatitis B surface antigen (HBsAg) CTL epitope. Enumeration of HBsAg-specific T cells producing cytokine indicated preferential induction of a Type 1 T helper cell response. These results provide the first demonstration of a DNA vaccine inducing protective antibody titers and both humoral and cell-mediated immune responses in humans.

Adult↗
PubMed1999

Phase 1 safety and immune response studies of a DNA vaccine encoding hepatitis B surface antigen delivered by a gene delivery device.

This study was designed to determine the safety and immunogenicity in volunteers of a DNA vaccine consisting of a plasmid encoding hepatitis B surface antigen delivered by the PowderJect XR1 gene delivery system into human skin. Seven healthy adult volunteers received two immunizations at one of three forces of delivery on day 0 and 56. The vaccine was well tolerated. One of six seronegative volunteers developed high titers of persistent HBsAb after a single immunization. In retrospect, this volunteer may have had previous exposure to hepatitis B. Our study suggests that the hepatitis B DNA vaccine given by this gene delivery system may induce a booster response, but the vaccine at the extremely low DNA dose used (0.25 microg) did not induce primary immune responses.

Adolescent↗
PubMed1998

The value of screening for psychiatric disorders prior to upper endoscopy.

Gastrointestinal (GI) complaints are among the most common symptoms in primary care yet are frequently unexplained and often lead to costly diagnostic testing. We sought to determine the prevalence of psychiatric disorders in patients with unexplained GI complaints undergoing upper endoscopy, and the likelihood of endoscopic abnormalities in patients with and without psychiatric diagnoses. We prospectively evaluated 116 adult patients who were undergoing upper endoscopy to evaluate GI complaints. All subjects received a structured psychiatric interview prior to endoscopy using PRIME-MD, and endoscopists were blinded to the PRIME-MD results. Psychiatric disorders were detected in 70 (60%) patients. Overall, there were 113 diagnoses (some patients had multiple disorders) with the most common being somatoform (44%), depressive (29%), and anxiety (19%) disorders. Only 29 patients had major endoscopic abnormalities, including esophageal disease (14), peptic ulcer (9), severe gastritis (4), gastric cancer (1), and esophageal cancer (1). There was a much higher prevalence of psychiatric disorders in patients without major endoscopic abnormalities (74% vs. 21%, p < 0.0001). Psychiatric disease was strongly predictive of endoscopic findings (OR for major abnormality = 0.11 in women, and 0.40 in men), especially if somatoform disorder was present (OR = 0.15). We conclude that, with a simple questionnaire, psychiatric disorders can be diagnosed in a large proportion of patients with unexplained GI complaints who are referred for upper endoscopy. The presence of a psychiatric disorder, particularly if somatoform, makes it unlikely that endoscopy will reveal significant GI disease.

Adult↗
PubMed1998

Restricted diastolic opening of the mitral leaflets in patients with left ventricular dysfunction: evidence for increased valve tethering.

OBJECTIVES: We tested the hypothesis that patients with incomplete systolic mitral leaflet closure (IMLC: apically displaced coaptation) also have restricted diastolic leaflet opening that is independent of mitral inflow volume and provides evidence supporting increased leaflet tethering. BACKGROUND: Competing hypotheses for functional mitral regurgitation (MR) with IMLC include global left ventricular (LV) dysfunction per se (reduced leaflet closing force) versus geometric distortion of the mitral apparatus by LV dilation (augmented leaflet tethering). These are inseparable in systole, but restricted leaflet motion has also been observed in diastole, and attributed to reduced mitral inflow. METHODS: Diastolic mitral leaflet excursion and orifice area were measured by two-dimensional echocardiography in 58 patients with global LV dysfunction, 36 with and 22 without IMLC, compared with 21 normal subjects. The biplane Simpson's method was used to calculate LV ejection volume, which equals mitral inflow volume in the absence of aortic regurgitation. RESULTS: The diastolic mitral leaflet excursion angle was markedly reduced in patients with IMLC compared with those without IMLC, whose ventricles were smaller, and normal subjects (17 +/- 10 degrees vs. 58 +/- 13 degrees vs. 67 +/- 8 degrees, p < 0.0001). Excursion angle was dissociated from mitral inflow volume (r2 = 0.04); excursion was reduced in patients with IMLC despite a normal inflow volume in the larger ventricles with MR (60 +/- 25 vs. 61 +/- 12 ml in normal subjects, p = NS), and excursion was nearly normal in patients without IMLC despite reduced inflow volume (40 +/- 10 ml, p < 0.001 vs. normal subjects). The anterior leaflet when maximally open coincided well with the line connecting its attachments to the anterior annulus and papillary muscle tip (angular difference = 3 +/- 7 degrees vs. 25 +/- 9 degrees vs. 32 +/- 10 degrees in patients with and without IMLC vs. normal subjects, p < 0.0001). In patients with IMLC, the leaflet tip orifice was smaller in an anteroposterior direction but wider than in the other groups, giving a normal total area (6.8 +/- 1.8 vs. 7.1 +/- 1.2 vs. 6.9 +/- 0.8 cm2, p = NS). CONCLUSIONS: Patients with LV dysfunction and systolic IMLC also have restricted diastolic leaflet excursion that is independent of inflow volume, coincides with the tethering line connecting the annulus and papillary muscle and reflects limitation of anterior motion relative to the posteriorly placed papillary muscles without a decrease in total orifice area. These observations are consistent with increased tethering by displaced mitral leaflet attachments in the dilated ventricles of patients with IMLC that can restrict both diastolic opening and systolic closure.

Adult↗
PubMed1996

Possibilities for unexplained chronic illnesses among reserve units deployed in Operation Desert Shield/Desert Storm.

Because Armed Forces Reserve members, especially combat support units, were rapidly mobilized during Operation Desert Shield/Desert Storm, they were at higher risk for anxiety and stress-related disorders. Personnel in reserve units in the military force structure are at greater risk for psychologic stress due to rapid mobilization and demobilization, which allows minimal time to process adverse experiences or fears. The unexpected disruption of families and careers and resulting financial pressures are magnified in older age groups who have increased personal and family commitments. Personnel in combat support units are at greatest risk when they lack necessary training, cohesion, and leadership. Prevention efforts in reserve units should involve education regarding the potential for activation and associated disruption of family and career plans. Support networks for reserve families should be encouraged. Additional training in an appropriate context regarding risks of biologic and chemical exposure, with the goal of developing confidence in training and equipment, should be stressed. Finally, group processing before demobilization and recall within 90 days of return to emphasize unit cohesion and readjustment to civilian life may be of benefit.

Chronic Disease↗
PubMed1995

When the physician leaves the patient: predictors of satisfaction with the transfer of care in a primary care clinic.

OBJECTIVE: To identify independent predictors of patients' satisfaction with transfer of their care from a departing to a new resident physician. DESIGN: A self-administered questionnaire completed by consecutive patients following up after transfer of their care, and by a randomly selected 50% of patients not returning within three months after transfer. SETTING: An internal medicine clinic in a teaching hospital. PATIENTS: Questionnaires were completed by 376 patients: 237 returning to clinic and 139 (91%) of 152 randomly selected patients who had not returned. Mean age of the patients was 65 years, 52% were men, and they had come to the clinic for a median of four years. RESULTS: 57% of the patients were satisfied with the transfer process, 25% were neutral, and 18% expressed frank dissatisfaction. Of nine variables significantly associated with satisfaction by univariate analysis, stepwise multiple regression identified five independent predictors. Personal notification of the patient by the departing physician was the most powerful determinant, explaining 41% of the variability in satisfaction. Other predictors were whether patients believed their physicians had done everything possible to facilitate transfer, whether the departing physician had provided opportunity for discussion of the transfer, whether this discussion was considered sufficient, and patients' impressions of the institution. CONCLUSIONS: Most of the predictors identified can be influenced by physician behavior, suggesting that physicians should personally notify patients of their departure and provide an opportunity for discussion. This could significantly improve patient satisfaction with the transfer process and, as previous studies suggest, translate into greater compliance with medications and follow-up.

Aged↗
PubMed1993

Absence of true seroreversion of HIV-1 antibody in seroreactive individuals.

OBJECTIVES: First, to determine whether there is evidence for loss of human immunodeficiency virus type 1 (HIV-1) antibody in seroreactive individuals. Second, if true seroreversion occurs, to determine its incidence relative to errors in the testing process. DESIGN: A retrospective cohort study reviewing the results of 5,446,161 HIV-1 antibody tests performed on 2,580,974 individuals (the US Army HIV Data System) from 1985 through 1992. For all patients with one or more seroreactive sample followed by one or more nonreactive sample, we examined available records and retested the samples. PARTICIPANTS: Serum samples had been obtained from active-duty and retired military personnel, their dependents, and applicants to the military. RESULTS: Of 4911 individuals reported to be seroreactive for HIV-1 by two independent samples, only six were potential seroreverters. Review of the six cases revealed that five actually were HIV-seroreactive patients who had samples from nonreactive individuals mistakenly attributed to them, while the sixth had a testing error proven by retesting the discrepant specimen. Errors in the testing process were identified (n = 23) or suspected (n = 3) in another 26 individuals who had not had independent confirmation of reactivity by a second sample. The cumulative error rate was 12.4 per 1 million patients tested. An additional group of 31 uninfected infants appeared to serorevert due to loss of antibody acquired from their HIV-1-infected mothers. CONCLUSIONS: Review of this database demonstrates no evidence for true seroreversion of HIV-1 antibody status. We conclude that if seroreversion occurs at all, it is exceedingly rare. In fact, most (if not all) cases of apparent seroreversion represent errors of attribution or testing.

AIDS Serodiagnosis↗
PubMed1993

The German health care system: model or mirage?

Rising costs have spurred America's leaders to look abroad for a model upon which to pattern reform of our health care system. On the surface, at least, Germany would appear to have an ideal system combining universal access, high quality, free choice of physicians, and cost control. Germany has been particularly effective in curbing pharmaceutical and administrative expenses, and has avoided the progressive imbalance between primary care providers and medical specialists seen in America. However, Germany lags behind the US in emphasizing preventive services and in shifting services to the ambulatory setting. Also, an oversupply of physicians, lack of incentives to limit the volume of services, and a global budget cap have combined to induce physicians to do more while their incomes were falling sharply relative to those of other workers. Although selected elements of the German health care system could be beneficial to America, full-scale adoption of the German system is neither realistic nor desirable.

Cost Control↗
PubMed1992

Efficacy of bovine milk immunoglobulin concentrate in preventing illness after Shigella flexneri challenge.

The protective efficacy of oral bovine immunoglobulin concentrates derived from colostrum against challenge with Shigella flexneri was studied in healthy adult volunteers in a randomized, double-blind fashion. Volunteers were given a product consisting of hyperimmune immunoglobulin concentrate with a high titer of anti-S. flexneri 2a lipopolysaccharide (LPS) with sodium bicarbonate or a control preparation with sodium bicarbonate three times a day for seven days. On the third day of treatment, volunteers received a challenge of 10(3) colony-forming units of S. flexneri 2a strain 2457T. None of the volunteers who received the high-titered hyperimmune product became ill, compared with 45% of volunteers who received the placebo (P less than 0.05). The duration of shedding of the challenge organism was decreased, and the active immune responses to S. flexneri LPS were less frequent and of lower magnitude in volunteers given the immunoglobulin concentrate than in those in the control group. High-titered, orally administered bovine immunoglobulin concentrate protects against shigellosis and may be useful in preventing shigellosis among travelers, military personnel, and individuals at risk during a Shigella outbreak.

Animals↗
PubMed1992

Histopathologic and immunohistochemical changes in gut-associated lymphoid tissues after treatment of rabbits with dexamethasone.

Corticosteroids cause impaired cell-mediated immunity which may encourage development of gastrointestinal and respiratory infections. In order to better understand the effects of corticosteroids on gastrointestinal immunity, immunological and histological changes in gut-associated lymphoid tissues were examined after intravenous administration of dexamethasone to rabbits. In treated animals, lymphoid domes and follicles were considerably reduced in size, and the dome epithelial layer was markedly depleted of M cells and lymphocytes. There were numerous open lesions at the luminal surface of dome epithelium, consistent with necrosis of M cells, and a striking depletion of follicular B cells in treated animals. These immunologic and histologic effects of corticosteroids could have found profound, deleterious effects on mucosal immune responses and host resistance to microbial infections.

Animals↗
PubMed1990

A novel surface antigen expressed by mature and activated rabbit T-lymphocytes.

The monoclonal antibody (Mab) 93C6 was used to identify a surface molecule expressed by mature and activated rabbit T-lymphocytes. This antigen was virtually absent in cells of the thymus (5% positive cells). All 93C6-positive cells expressed the rabbit pan-T marker L11-135 and proliferated in response to concanavalin A (Con A). When lymphocytes were activated in the presence of Con A, the expression of the 93C6 molecule was quantitatively increased. Con A stimulation alone did not markedly enhance expression of this antigen by thymocytes, but stimulation with both Con A and interleukin-2 (IL-2) resulted in a population of thymocytes that expressed the antigen in a manner quantitatively similar to that of mature T-cells in other tissues.

Animals↗
PubMed1987

Precocious development of lectin (Ulex europaeus agglutinin I) receptors in dome epithelium of gut-associated lymphoid tissues.

Dome epithelium (DE), the tissue covering lymphoid domes of gut-associated lymphoid tissues, was examined in both adult and neonatal rabbit appendix or sacculus rotundus to determine if dome epithelial cells matured earlier than epithelial cells covering adjacent villi. The localization of well-differentiated epithelial cells in rabbit gut-associated lymphoid tissues (GALT) was accomplished histochemically by use of molecular probes: fluorescein isothiocyanate or horseradish peroxidase conjugates of Ulex europaeus agglutinin I (UEA), a lectin specific for terminal L-fucose molecules on certain glycoconjugates. The villus epithelial cells of newborn and 2-, 5-, or 10-day-old rabbits did not bind UEA, but between the twelfth and fifteenth days of postnatal life, UEA receptors were expressed by well-differentiated villus epithelial cells. In contrast to villus epithelium, DE in appendix and sacculus rotundus of neonatal rabbits expressed UEA receptors two days after birth, a feature that distinguished the DE of neonatal GALT for the next two weeks. In adult rabbits, UEA receptors were associated with dome epithelial cells extending from the mouths of glandular crypts to the upper domes; in contrast to the domes, UEA receptors were only present on well-differentiated epithelial cells at the villus tips. Results suggested that in neonatal rabbits most dome epithelial cells developed UEA receptors shortly after birth, reflecting precocious development of DE as compared to villus epithelium. In adult rabbit dome epithelium UEA receptors appeared on dome epithelial cells as they left the glandular crypts, representing accelerated epithelial maturation.

Animals↗
PubMed1987

A novel antigen is common to the dome epithelium of gut- and bronchus-associated lymphoid tissues.

The dome epithelium (DE) covering bronchus- and gut-associated lymphoid tissues (BALT and GALT) is composed of columnar cells, groups of lymphocytes, M cells, and pre-M cells. Although the cell biology and immunologic processes of this tissue are likely important in the afferent arm of secretory immune responses, virtually nothing is known about biochemical constituents of the DE. Therefore, a monoclonal antibody, 30E5, was used to study the distribution of a novel antigen, common to dome epithelia of GALT and BALT. 30E5 was secreted by a hybridoma, prepared by fusing murine splenocytes, immunized against dome epithelial cells, with P3 X 68/Ag8 myeloma cells. Reactivity of antigens was defined by indirect immunocytochemistry on sections of rabbit tissues or with dissociated epithelial cells. In situ, 30E5-reactive antigen circumscribed each group of dome epithelial lymphocytes, most or all of which were T cells, in rabbit appendix, sacculus rotundus, cecal patch, Peyer's patch, and BALT. In the DE this antigen was associated with the apical surface and the supranuclear or perinuclear regions of epithelial cells, but it was not associated with epithelial cells of villi, epithelium, or with individual lymphocytes. In peripheral lymph nodes, spleen, and in domes and follicles of GALT or BALT, 30E5-reactive antigen was visualized in linear wisps, primarily in regions populated by thymocytes. In other adult tissues, 30E5-reactive antigen was associated with involuntary muscle, myoepithelial cells of lactating mammary gland and with what appeared to be neural dendrites; but it was not found in epithelia other than DE. In neonatal rabbit appendix, this antigen first appeared in the upper dome epithelium two days after birth, a period coinciding with T cell infiltration and M cell maturation. The histologic distribution of 30E5-reactive antigen suggested that it might be a contractile filament, a receptor, or a differentiation antigen. Since 30E5 was associated with DE of both GALT and BALT, results support the concept of a molecule common to all mucosa-associated lymphoid tissues.

Animals↗
PubMed1987

Development of dome epithelium in gut-associated lymphoid tissues: association of IgA with M cells.

The dome epithelium (DE), which covers gut-associated lymphoid tissues (GALT) and provides both a protective barrier over lymphoid follicles and a route for antigen uptake from the gut, develops in rabbit appendix (caecum) during the first week of neonatal life. To determine if secretory immunoglobulins from maternal milk interact with this developing tissue, their interrelationships in neonatal rabbit appendix were examined by use of immunocytochemical techniques. The glycoprotein, secretory component, was not produced by neonatal rabbits less than 15 days old, since neither the membranous nor the free, secreted forms of maternal secretory component were associated with villi or DE of neonates. Immunoglobulin A (IgA), but neither IgG nor IgM, were noted on DE by light microscopy, even though IgG was abundant in the villus lamina propria and vascular spaces. The epithelial IgA was distributed, in a patchy pattern, across the upper dome surface of some two-day-old, and all five-and ten-day old nursing animals, but IgA was not on DE of rabbits prevented from nursing. Immuno-electron microscopy of appendix from nursed rabbits revealed IgA directly over the apical surface of M cells, where it formed a continuous, thick coating without binding to adjacent immature absorptive cells; it was also within apical vacuoles of M cell cytoplasm. The distribution of IgA on the DE of rabbit appendices indicated that in differentiating GALT, maternal IgA reacted preferentially with M cells or pre-M cells, leading to speculation concerning a role for IgA in the development of GALT and in establishment of mucosal immune responses in neonates.

Aging↗
PubMed1987

Diagnosis of spontaneous Clostridium spiroforme iota enterotoxemia in a barrier rabbit breeding colony.

Five New Zealand White rabbits (Oryctolagus cuniculus) in a rigid barrier rabbit breeding colony developed acute diarrhea 1 week after weaning. Both Clostridium spiroforme and an iota-toxin were isolated from cecal and colon contents of all five rabbits. When pure isolates of C. spiroforme were administered to two normal healthy rabbits, the rabbits developed identical disease and shed both the organism and the iota-toxin. Results of this study suggested that C. spiroforme is an important enteric pathogen of weanling rabbits and the etiology of this diarrhea complex can be rapidly confirmed using four diagnostic criteria.

Animals↗