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Biomedical subjects

J Ross

Publications and source records attributed to J Ross.

At least 361 records · Page 20Linked to original sources

The differential effects of donor versus host Langerhans cells in the rejection of MHC-matched corneal allografts.

The fate of MHC-identical, multiple minor H-disparate corneal grafts was examined in the rat. Although skin grafts exchanged between LEW and F344 rats were invariably rejected, only 26% of the corresponding corneal grafts underwent rejection. The immunologic privilege of the minor H-disparate corneal grafts was due, at least in part, to the absence of donor-derived Langerhans cells. Corneal grafts were normally devoid of donor-derived Langerhans cells; however, grafts pretreated with latex beads became infiltrated with donor-derived Langerhans cells and were rejected by 59% of the naive minor H--compatible recipients. By contrast, untreated LEW corneal grafts underwent rejection in 26% of the naive F344 hosts even though the grafts became heavily infiltrated with host-derived Langerhans cells. The immunologic privilege of minor H-disparate corneal grafts was not the result of efferent blockade or suppression of the immune response. F344 hosts bearing long-term surviving LEW corneal allografts were challenged with LEW skin grafts. In all cases, orthotopic skin grafts were rejected acutely. Moreover, all previously clear corneal grafts underwent rejection following skin graft rejection. Thus, the unique absence of donor-derived Ia+ passenger cells and the avascular graft bed conspire to provide the primary minor H-disparate corneal graft with an immunologic privilege not shared by other organ grafts.

Animals↗

HIV-related knowledge, beliefs, and behaviors among high school students in the United States: results from a national survey.

The Secondary School Student Health Risk Survey measured the prevalence of sexual intercourse and illegal drug injection among a national probability sample of U.S. high school students and assessed their HIV-related knowledge and beliefs. Ninety-nine (81%) of the 122 selected schools and 8,098 (83%) of the eligible students participated. Nearly all high school students knew the major modes of HIV transmission. Three percent reported injecting illegal drugs, and 1% reported sharing needles used to inject drugs. In addition, 59% of students reported having sexual intercourse and, of students who reported having sexual intercourse, 40% reported having four or more sexual partners. HIV-related knowledge, beliefs, and behaviors among high school students suggest the need for school-based HIV education programs that help young people acquire the knowledge and skills to adopt and maintain behaviors that reduce risk of HIV infection and other related health problems.

Adolescent↗

An in vitro transcription analysis of early responses of the human immunodeficiency virus type 1 long terminal repeat to different transcriptional activators.

In this report we introduce a simple, fast, and reliable method to prepare whole cell or nuclear extracts from small numbers of cells. These extracts were used to study transcriptional activation of the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) in vitro. Our results revealed that the time courses of activation of extracts derived from cells stimulated with the mitogenic lectin phytohemagglutinin (PHA) or with the tumor promoter phorbol 12-myristate 13-acetate (PMA) are different. PMA induces a rapid onset of increased in vitro transcription from the HIV-1 LTR, while PHA causes a slow and sustained response. The biochemical relevance of protein synthesis inhibition by cycloheximide treatment of cells was investigated. In these studies, PMA induction of a change in in vitro transcriptional activity is not dependent on protein synthesis. Cycloheximide alone is insufficient to induce activation. Oligonucleotide-mediated site-directed mutagenesis demonstrated that mutation of the TATA box in the LTR ablated initiation of both basal-level transcription and activation by extracts from cells stimulated with PMA. Surprisingly, mutation of both kappa B sites in the LTR reduced but did not eliminate the in vitro response to extracts prepared at early time points after PHA or PMA stimulation of Jurkat cells. The reduction was greater in extracts derived from cells treated with PMA. Deletion analysis of the HIV-1 LTR revealed at least one region (-464 to -252) capable of suppressing in vitro transcription in extracts from Jurkat cells stimulated by PMA. This result is consistent with early studies of the HIV-1 LTR in transient transfection assays. We therefore have been able to observe distinct regulatory events at early time points after cells are exposed to agents known to induce transcription of both the HIV-1 LTR reporter gene constructs and the HIV-1 provirus itself.

Cell Line↗

An analysis of false positive reactions occurring with the Captia Syph G EIA.

AIM: The Captia Syph G enzyme immuno assay (EAI) offers the potential for the rapid automated detection of syphilis antibodies. This study was designed to assess the role of other sexually transmitted diseases (STDs) in producing false positive reactions in the Captia Syph G EIA. The role of rheumatoid factor (RF) as a potential source of false positives was also analysed. METHODS: Patients who attended a genitourinary medicine (GUM) department and gave a false positive reaction with the EIA between 1988 and 1990 were compared with women undergoing antenatal testing and with the control clinic population (EIA negative) over the same time period. The incidence of sexually transmitted disease (STD) in the clinic population and the false positive reactors was measured in relation to gonorrhoea, chlamydia, genital warts, candidiasis, "other conditions not requiring treatment" and "other conditions requiring treatment." Male: female sex ratios were also compared. Ninety two RF positive sera were analysed with the EIA. RESULTS: The rate of false positive reactions did not differ with respect to the diagnosis within the GUM clinic population. The antenatal group of women, however, had a lower incidence of false positive reactions than the GUM clinic group. No RF positive sera were positive on Captia Syph G EIA testing. CONCLUSIONS: There is no cross reaction between Captia Syph G EIA and any specific STD or with RF positive sera. The lower incidence of false positive reactions in antenatal women is unexplained but may be related to physiological changes associated with pregnancy.

False Positive Reactions↗

Heart rate reduction improves myocardial ischemia in swine: role of interventricular blood flow redistribution.

Regional myocardial blood flow (MBF) distribution and function upon slowing the heart rate (HR) during ischemia were studied in anesthetized swine, a species without coronary collaterals. Perfusion of the left anterior descending artery by a pump allowed controlled production of regional ischemia. Slowing tachycardia by electrical pacing (127 to 87 beats/min) caused marked improvement of regional dysfunction [% wall thickening (WTh) from 9 to 27%] and increased subendocardial MBF [from 0.31 to 0.55 ml.min-1.g-1 (P less than 0.001)] without change of subepicardial MBF. Total left ventricular (LV) MBF increased, whereas right ventricular (RV) MBF fell by 18% (P less than 0.02). The mechanism of MBF changes during slowed HR was assessed by surgically excluding the RV and comparing findings with previous experiments with RV intact when HR was slowed from 96 to 60 beats/min. A similar improvement of regional LV function occurred (8% vs. 30% WTh) with the RV excluded, but without a change in total flow to the LV bed, whereas subendocardial MBF increased and subepicardial MBF fell, indicating transmural redistribution only. These findings show that the RV vascular bed can contribute to LV perfusion in swine during ischemia, and they document the potential for "reverse RV steal" during slowed heart rate in this setting.

Animals↗

Myocardial perfusion-contraction matching. Implications for coronary heart disease and hibernation.

Experimental studies demonstrate that short-term regional perfusion-contraction matching, in which the energy demands of regional myocardial contraction are reduced to match the diminished myocardial substrate supply, occurs during states of low coronary blood flow under resting conditions and during exercise-induced ischemia. This phenomenon is rapidly reversible and appears to occur in several clinical settings. Sustained perfusion-contraction matching is observed in states of partial experimental ischemia of intermediate duration lasting several hours. This condition might be called short-term hibernation and resembles clinical conditions such as unstable angina pectoris or myocardial infarction with some residual perfusion in which the contractile defect can be improved by reperfusion provided the ischemia is not severe enough to cause transmural necrosis. Such experimental and clinical observations may or may not relate to the setting of regional dysfunction at rest in patients with chronic coronary heart disease, in whom manifestations of acute ischemia may be absent but improvement of wall motion abnormalities occurs after CABG or balloon angioplasty. This condition may constitute the hypothetical state of chronic myocardial hibernation, for which tentative evidence exists from metabolic and perfusion studies using PET. Whether such a condition of prolonged perfusion-contraction matching might be associated with adaptive processes that could allow its persistence for long periods without manifest ischemia remains to be investigated.

Animals↗

Trends in use of coronary angiography in subacute phase of myocardial infarction.

BACKGROUND: Most patients do not undergo acute reperfusion after myocardial infarction, and which of these patients should undergo coronary angiography is still debated. METHODS AND RESULTS: We analyzed the 1-year clinical outcomes and rates of coronary angiography performed as late as 60 days after myocardial infarction in 3,804 patients admitted between 1979 and 1988 and followed in six different centers. Patients less than 75 years old were classified into low-, medium-, and high-risk groups using a multivariate analysis of historical and clinical variables gathered during the first 8 hospital days. Patients who underwent early reperfusion (17%, all after 1984) were analyzed separately. To analyze time trends, patients were compared before and after mid-1984. Mortalities from day 9 through 1 year were similar for the two time periods in the low- (3.3% versus 2.5%) and medium-risk (7.4% versus 5.6%) groups, but mortality was lower for the high-risk group after 1984 (31.6% versus 20.0%). The proportion of patients undergoing coronary angiography increased dramatically in each group after 1984 (low risk, 18% versus 48%; medium risk, 23% versus 49%; high risk, 10% versus 32%, before and after 1984, respectively). Furthermore, a large percentage of patients (more than 40%) in the low-risk group did not have at least one of the indications for coronary angiography recently recommended by a joint task force. Among patients undergoing coronary angiography, the proportion of patients with three-vessel coronary artery disease decreased after 1984, whereas the proportion undergoing mechanical revascularization in the year after infarction increased in all risk groups. CONCLUSIONS: Despite the recent development of noninvasive techniques with high sensitivity for detecting high-risk patients after myocardial infarction, coronary angiography is being performed increasingly in all patients, including those determined to be at low risk for complications based on clinical data. The economic consequences of such a trend could be considerable, and its impact requires careful analysis.

Age Factors↗

Effect of alpha-adrenergic stimulation on regional contractile function and myocardial blood flow with and without ischemia.

BACKGROUND: The effect of alpha-adrenergic receptor activation on regional contractile function and transmural myocardial blood flow is controversial. Accordingly, the effects of selective alpha 1-(methoxamine) and alpha 2-(BHT 933) receptor stimulation on regional contractile function and transmural myocardial blood flow distribution were studied in 15 anesthetized open-chest dogs. METHODS AND RESULTS: The alpha-adrenergic agonists were separately infused into the cannulated left circumflex coronary artery during control and ischemic conditions in the same animal. Mean coronary perfusion pressure was held constant by a servocontrolled pump in an extracorporeal circuit. Ischemia was created by reducing coronary perfusion pressure to the level at which percent systolic wall thickening (%WT) decreased by 54%. Contractile function during control conditions was unchanged, whereas under ischemic conditions a further significant decrease in %WT of 27% occurred with either alpha 1- or alpha 2-receptor stimulation without any change in the anterior (control) wall function. Both alpha 1- and alpha 2-receptor stimulations during control conditions resulted in a relatively uniform transmural decrease in blood flow with no change in the subendocardial-to-subepicardial blood flow ratio. With alpha 1-stimulation during ischemia (n = 13), there was a tendency toward decreased subepicardial blood flow with no change in subendocardial flow, resulting in an increased subendocardial-to-subepicardial blood flow ratio (0.61 +/- 0.23 to 0.82 +/- 0.40, p less than 0.05). alpha 2-Receptor stimulation during ischemia (n = 12) produced a significant decrease in subepicardial blood flow (0.45 +/- 0.20 to 0.35 +/- 0.12 ml/min/g, p less than 0.01) with no change in subendocardial blood flow, also resulting in an increased subendocardial-to-subepicardial blood flow ratio. CONCLUSIONS: These results indicate the selective vasoconstriction in outer wall layers during ischemia mediated by either alpha 1- or alpha 2-receptors can cause a decrease in regional contractile function despite unchanged subendocardial blood flow and improved subendocardial-to-subepicardial flow ratio. This suggests an adverse effect of alpha-adrenergic vasoconstriction during ischemia in this coronary perfusion pressure-controlled canine model.

Adrenergic alpha-Agonists↗

Pulmonary function in individuals with a history of poliomyelitis.

We examined the relationship between the lung function of 74 individuals with a history of poliomyelitis and reports of shortness of breath during activities of daily living, and the presence of post-polio sequelae risk factors. First, we studied the spirometry of 60 individuals (group 1) and second, we studied the relationship between the spirometry of an additional 14 individuals (group 2) and their respiratory muscle strength (Pimax and Pemax). In both groups, we examined the relationship between factors associated with post-polio sequelae including ventilation at polio-onset, having contracted polio after the age of 10, and having had polio for over 35 years; and lung function. In group 1, the FEV1 and FVC were lower for individuals with shortness of breath than individuals without (p less than 0.01). With respect to risk factors, FEV1 and FVC were lower in individuals who were ventilated at polio-onset, in individuals who contracted polio over 10 years of age, and in individuals who had had polio for less, rather than more than 35 years (p less than 0.05). The results for group 2 were comparable to group 1. In addition, the observed Pimax and Pemax were significantly lower than predicted values (p less than 0.05). Although FEV1 and FVC were positively correlated with both Pimax and Pemax (p less than 0.05), Pemax was disproportionately impaired compared to Pimax (40 +/- 12.1 and 82 +/- 38.8 percent predicted respectively). We conclude that individuals with a history of poliomyelitis can have compromised lung function irrespective of shortness of breath, that risk factors such as ventilation at polio-onset and polio-onset after 10 years of age can help predict those at risk of respiratory compromise, and that the measurement of respiratory muscle strength and of Pemax in particular, can augment the assessment of lung function of these individuals. Such assessment may avert respiratory complications in the post poliomyelitis population including those secondary to health care interventions.

Adult↗

Class I disparate corneal grafts enjoy afferent but not efferent blockade of the immune response.

Class I antigens are normally expressed on cells in all three layers of the cornea. In congenic rats that differ only at the single Class I locus RT1 A, central orthotopic corneal grafts were rejected 18% of the time with a mean survival time (MST) of 11.5 days. Pre-immunized recipients always rejected Class I disparate corneal grafts (100%, MST = 13.3 days). Surprisingly, the presence of donor Langerhans cells in the cornea at the time of grafting did not increase the rejection of grafts (20%, MST = 14.0 days). To determine if long term surviving grafts enjoyed immune priviledged in the form of efferent blockade, the recipients were challenged with skin grafts 4 to 6 weeks following corneal transplantation. All of the corneal grafts underwent rejection (100%, MST = 14.7 days). A number of important conclusions may be drawn from these studies. A single Class I mismatch is a weak barrier to successful engraftment of corneal grafts. However if the recipient has previously been exposed to donor antigens, a single Class I disparity is sufficient to provoke rejection of all subsequent corneal grafts. The susceptibility of long term surviving grafts to rejection induced by skin grafts indicates the orthotopic corneal grafts are antigenic but not immunogenic.

Afferent Pathways↗

Effect of modified aerobic training on movement energetics in polio survivors.

Given that individuals with disabilities may be unable to achieve maximal oxygen uptake in an exercise test and that maximal exercise testing may cause increased fatigue, pain, and muscle weakness, we examined the role of submaximal exercise testing and training based on objective as well as subjective parameters in polio survivors. Experimental (N = 7) and control subjects (N = 13) were tested before and after a 6-week period. The experimental subjects participated in a 6-week exercise training program for 30 to 40 minutes, three times a week. The program consisted of treadmill walking at 55% to 70% of age-predicted maximum heart rates; however, exercise intensity was modified to minimize discomfort/pain and fatigue. Neither objective nor subjective exercise responses were significantly different in the control group over the 6 weeks. No change was observed in cardiorespiratory conditioning in the experimental group. However, movement economy, which is related to the energy cost of walking, was significantly improved; and walking duration was significantly increased at the end of training. Modified aerobic training may have a role in enhancing endurance and reducing fatigue during activities of daily living in polio survivors.

Adult↗

Promotion of murine orthotopic corneal allograft survival by systemic administration of anti-CD4 monoclonal antibody.

A mouse model of orthotopic corneal allograft rejection was used to examine the efficacy of anti-CD4 and anti-CD8 monoclonal antibodies in preventing immunologic rejection of corneal allografts. Although it is believed by many that corneal graft rejection is mediated, at least in part, by CD8-positive cytotoxic T-lymphocytes, systemic administration of anti-CD8 antibody did not reduce the rejection rate of corneal allografts that differed from the host at the entire major histocompatibility complex. By contrast, systemic administration of anti-CD4 monoclonal antibody reduced the rejection rate from 83% (untreated controls) to 33%. Fluorocytometric analysis of residual lymphoid populations showed that neither monoclonal antibody eliminated the inappropriate subset of T-cells in antibody-treated animals. In vitro cell-mediated cytotoxicity assays showed that both antibodies eliminated allospecific cytotoxic T-lymphocyte populations; however, only anti-CD4 antibody promoted graft survival. Thus, these results indicate that anti-CD4 monoclonal antibody is a powerful immunosuppressive agent for promoting corneal graft survival and that CD8-positive T-cells alone do not cause rejection of corneal allografts.

Animals↗

Social phobia: the Anxiety Disorders Associated of America helps raise the veil of ignorance.

Social phobias affect some 2.4 million American adults, and more than 5 million can expect to develop a social phobia during their lifetime. Despite their prevalence, social phobias have been virtually ignored until this past decade. The Anxiety Disorders Association of America (ADAA) was founded in 1980 to promote awareness among professionals and the public of anxiety disorders. This paper outlines the objectives of ADAA and its programs, including the Self-Help Group Network, helpful publications, and its partnership with psychiatrists and patients. The benefits of self-help programs to persons with social phobias are illustrated, including the role played by the clinician in evaluation and referral. The ADAA program for the 1990s focuses on the education of all health professionals and the creation of awareness of economic costs of undiagnosed anxiety disorders.

Adult↗

An outbreak of methicillin-resistant Staphylococcus aureus in a pediatric hospital--how it got away and how we caught it.

An outbreak of methicillin-resistant Staphylococcus aureus (MRSA) occurred in a hospital without endemic MRSA, following the transfer of a patient colonized by MRSA from another hospital known to have a problem with endemic MRSA. Despite initial appropriate isolation and therapy to eradicate colonization of the organism, the index child relapsed 10 weeks after the last prior positive culture. Simultaneously, the organism was isolated from two other patients on the same ward, and subsequently at surgery from one child transferred to the neonatal intensive care nursery. Antimicrobial therapy for urinary tract infection likely impaired earlier identification of MRSA in the index case. Suppression with mupirocin rather than eradication may have resulted in inappropriate early discontinuation of infection control precautions. Control of the outbreak and eradication of the organism from all patients was successful after intensive surveillance and control measures, including strict isolation and cohorting. This outbreak suggests that infection control precautions and intensive screening of contacts, as well as positive cases, may be effective for control and eradication of MRSA from health care facilities with recent introduction of an epidemic strain.

Child, Preschool↗