Biomedical subjects

A Friedman

Publications and source records attributed to A Friedman.

At least 109 records · Page 6Linked to original sources

PubMed1995

Laminar pattern of synaptic inhibition during convulsive activity induced by 4-aminopyridine in neocortical slices.

1. Epileptiform activity was induced in rat neocortical brain slices by application of a low concentration (10 microM) of 4-aminopyridine (4-AP). In intracellular recordings from regular spiking neurons, the activity was characterized by prolonged, all-or-none depolarizing events, with variable delay to a threshold stimulus. 2. At this concentration, 4-AP had no measurable effect on passive electrical properties or on action-potential characteristics. 3. Paroxysmal responses in neurons of deeper layers differed markedly from those of superficial cells. In deep neurons, responses resembled those generated by neocortical neurons exposed to GABAergic blockers. A low-intensity stimulus to the white matter evoked an excitatory postsynaptic potential (EPSP) that was followed with variable latency by a paroxysmal depolarizing shift that reversed at suprathreshold membrane potentials and upon which superimposed repetitive firing was always evident. By contrast, in superficial (layer II-III) neurons, the same stimulus evoked an EPSP that was followed by a prolonged response whose late component reversed at subthreshold membrane potentials (between -50 and -80 mV). These cells rarely fired more than a single spike throughout the response. 4. Repetitive stimulation at relatively low frequencies (0.3-1 Hz) caused a gradual change in the synchronized responses that was most marked in superficial neurons. The reversal potential of the response shifted toward suprathreshold membrane potentials, and subsequently, superimposed repetitive firing became evident. These changes were not associated with measurable changes in input resistance or membrane potential.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Aminopyridine↗

PubMed1995

Effect of dietary fatty acids on antibody production and fatty acid composition of lymphoid organs in broiler chicks.

This study examined the effect of increasing amounts of dietary polyunsaturated fatty acids on antibody production in vivo and fatty acid composition of plasma and lymphoid tissues in the broiler. Chicks were fed four diets containing 12% added fat made up of different proportions of palm oil and soybean oil and immunized against bovine serum albumin at 14 to 16 d of age. Blood samples were taken every 4 to 5 d for 30 d; then the chicks were killed and liver, spleen, thymus, bursa of Fabricius, and bone marrow were sampled. Fatty acid composition in serum and tissues reflected the composition of the diets, although amounts of saturated fatty acids were tissue-specific. Arachidonic acid concentration was not changed by dietary fatty acid content. Antibody production developed more rapidly, reached a higher level, and was more persistent in the chicks fed lower levels of linoleic acid. A quadratic relationship was found between tissue linoleic acid or total polyunsaturated fatty acid concentrations and antibody production at 11 and 14 d after challenge. No correlation was found with arachidonic acid. It is concluded that dietary fatty acid composition can influence immune response in broilers.

Animals↗

PubMed1995

The restoration of elbow flexion with intercostal nerve transfers.

Seventeen patients with absent elbow flexion secondary to brachial plexus avulsion injury underwent intercostal neurotization of the biceps muscle. Followup was performed at an average of 5 years. The average age in this series was 21.8 years; the mean time interval from injury to the surgical procedure was 6 months. Eight of the 17 patients (47%) obtained good or excellent results as defined by Nagano et al. Five patients had muscle function ratings of M2 but were unable to power the elbow against gravity. The overall success rate theoretically may be increased by (1) decreasing the time interval from injury to neurotization to < 5 months; (2) selecting patients < 50 years of age; and (3) using adjuvant surgical procedures after neurotization, including tendon transfers and shoulder arthrodesis, which may improve results from good to excellent.

Adolescent↗

PubMed1994

Induction of anergy or active suppression following oral tolerance is determined by antigen dosage.

Oral tolerance was generated to hen egg white lysozyme in the mouse or to guinea pig myelin basic protein in the rat by a low-dose (1 mg) or a high-dose (5-20 mg) feeding regimen. High doses of antigen induced tolerance characterized by anergy with little or no active suppression and increased secretion of interleukin 4 (IL-4). Anergy was shown by an increase in frequency of IL-2-secreting cells following culture in recombinant IL-2. Low doses of antigen induced tolerance characterized by antigen-driven active suppression with increased secretion of transforming growth factor beta (TGF-beta) and IL-4 and minimal anergy. Without further immunization, spleen cells from animals orally tolerized by both regimens secreted increased levels of IL-4 and TGF-beta in an antigen-specific manner. Animals fed high doses secreted more IL-4 and less TGF-beta, whereas those fed low doses secreted more TGF-beta and less IL-4. These results demonstrate that the two feeding regimens induced cell populations that differed in their cytokine secretion profile and their capacity to actively suppress in vitro and to induce anergy. Our results provide a basis for distinguishing different forms of antigen-driven peripheral tolerance and have important implications for orally induced antigen-specific modulation of human autoimmune diseases.

Administration, Oral↗

PubMed1994

In vivo tolerization of Th1 lymphocytes following a single feeding with ovalbumin: anergy in the absence of suppression.

Oral tolerance is a biologically relevant pathway for inducing peripheral tolerance to foreign antigens. The mechanisms responsible for the tolerant state following feeding with antigen have been shown to involve both anergy and suppression. The demonstration of anergic T lymphocytes following oral tolerance has so far been limited in in vitro systems, and a primary objective of the present study was to provide evidence, in vivo, for the existence of a state of anergy in mice orally fed with ovalbumin (OVA). In addition, it has been shown that peripheral anergy following the intravenous administration of antigen is selectively induced in Th1 lymphocytes. Thus, a second objective of this study was to investigate whether tolerance induced by a feeding regimen known to cause anergy could be selectively limited to Th1 lymphocytes, and whether tolerance induction could be explained by antigen absorption from the gut into the circulation. Oral tolerance was induced by a single feeding with OVA, and was demonstrated by diminished antibody production in vivo, and by reduced cytokine secretion or proliferation in vitro. Anergy, as a mechanism for tolerance, was demonstrated by the ability to reverse the tolerant state after culturing tolerant cells in recombinant interleukin-2 (rIL-2). Reversal of the tolerant state in vivo was established by antibody production in irradiated mice adoptively transferred with cells cultured in the presence of rIL-2. The possibility that suppression was also an in vivo mechanism for tolerance was studied by adoptive transfer experiments. Our results show: 1) that a single dose of orally administered OVA leads to the selective tolerization of Th1 responses (diminished IgG2a, IL-2 and interferon-gamma production) with intact Th2 responses (IgG1, and IL-4), 2) that tolerance in vivo is explained by anergy in the absence of active suppression, 3) that exposure of tolerant cells to rIL-2 in vitro abrogates the anergic state both in vitro (proliferation and cytokine secretion) and in vivo (IgG2a production), and 4) that the induction of oral tolerance is inhibited by the presence of antibodies specific for the tolerizing antigen. These findings indicate that the induction of anergy via the oral route might depend on the dissemination of antigen absorbed from the gut. It is suggested that tolerance is guaranteed by the fact that this absorbed antigen is presented to Th1 lymphocytes in the absence of inflammatory and co-stimulatory molecules; these foreign antigens are thus not different from self antigens.

Administration, Oral↗

PubMed1994

Different kinetic patterns of cytokine gene expression in vivo in orally tolerant mice.

A biologically relevant mechanism of generating peripheral tolerance in T cells that have escaped thymic deletion is by the oral administration of soluble antigens. Oral tolerance occurs by two distinct mechanisms. Feeding a single high dose of antigen induces anergy of antigen-specific TH1 cells, while multiple low doses of antigen induce regulatory T cells that mediate suppression by producing immunosuppressive cytokines. Although cytokine production orally tolerant animals has been well studied utilizing in vitro assay systems, semi-quantitative characterization of cytokine production in oral tolerance in vivo has not been carried out. In this paper we have developed a system using semi-quantitative RNA polymerase chain reaction to characterize cytokine gene expression in vivo in mice orally tolerized by feeding either a single high dose or multiple low dosages of antigen. We find that measurable differences in interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) gene expression occurred between the tolerized and non-tolerized groups. Qualitatively, IL-4 mRNA was increased in both orally tolerized groups. However, significant differences in IL-4 gene expression between the two groups in both magnitude and kinetics were found. A large but short-lived increase in IL-4 was produced in mice fed a single high dose, while a relatively more moderate, longer-lived increase was produced in mice fed multiple low doses. The increase in IL-4 gene expression was specific only to the draining lymph node following antigen administration. Expression of IFN-gamma was decreased in both orally tolerant groups. These results indicate that tolerance in TH1 cells is induced by both of these feeding regimens while TH2 responses are intact and amplified upon reexposure to antigen.

Administration, Oral↗

PubMed1994

Protective immunity by intramuscular injection of low doses of influenza virus DNA vaccines.

Dose-response relationships were investigated between dose of influenza virus haemagglutinin (HA) or nucleoprotein (NP) DNA vaccines, and immunogenicity and protective efficacy based on humoral and cellular immunity. In mice, intramuscular (i.m.) injection of HA or NP DNA, at doses of 100 ng to 1 microgram, was found to generate haemagglutination inhibiting (HI) antibodies and cytotoxic T-lymphocytes, respectively, and provide protection in influenza virus challenge models. A direct correlation between the amount of DNA injected and the level of HI antibody was observed. In non-human primates, high-titre neutralizing antibodies were induced in animals vaccinated with as little as 10 micrograms of HA DNA. These results indicate that low doses of DNA administered by i.m. injection provide protective efficacy against influenza.

Animals↗

PubMed1994

Retinoic acid receptor-alpha gene expression is modulated by dietary vitamin A and by retinoic acid in chicken T lymphocytes.

The effects of dietary vitamin A and retinoic acid in vitro on the proliferative response and gene expression of retinoic acid receptor-alpha (RAR-alpha) in chicken T lymphocytes were studied. Antigen-specific proliferative responses of T lymphocytes increased with dietary vitamin A intake from 0 to 6.6 mg/kg diet; however, at high dietary vitamin A (13.2 mg/kg diet), the proliferative response declined. RAR-alpha mRNA expression in T lymphocytes peaked in chicks fed low levels of vitamin A (830 and 1500 micrograms/kg diet) and declined at higher intakes. In vitro effects of retinoic acid on the modulation of RAR-alpha mRNA were studied in stimulated T lymphocytes. Retinoic acid (0.01 mumol/L) increased RAR-alpha mRNA levels within 2 or 16 h of incubation with concanavalin A- or beta-casein-stimulated T cells, respectively. This effect was transient. Expression of RAR-alpha mRNA in concanavalin A-stimulated T lymphocytes was up-regulated by retinoic acid in a dose-dependent manner, and maximal expression occurred in response to 1 mumol/L retinoic acid. The proliferative response of these cells was also modulated by retinoic acid in a dose-dependent manner, and highest effects were observed at 0.01 mumol/L retinoic acid. Our results indicate that RAR-alpha mRNA expression and antigen-specific proliferative responses of T lymphocytes are influenced by vitamin A status in vivo, and directly modulated by retinoic acid.

Administration, Oral↗

PubMed1994

The role of preserved autogenous cartilage graft in septorhinoplasty.

Previous reports have established the role of fresh autogenous cartilage grafts harvested at the time of surgery. This report describes the value of autogenous preserved cartilage, removed and stored at the time of initial surgery, for use in secondary surgery. This study also compares fresh and preserved cartilage used in crushed and noncrushed states in secondary rhinoplasties. From 1983 to 1990, 256 of 1,185 patients who had undergone septorhinoplasty required a revision procedure. Cartilage graft was used in 186 (72.7%) patients. Cartilage removed during the primary surgery was stored in a saline and antibiotic solution at 0 degree F to 2 degrees F. The average time interval from primary to secondary surgery was 11.97 months (SD, 10.63 mo). Follow-up after graft placement averaged 44.71 months (SD, 26.21 mo). Two hundred seventy-seven pieces of cartilage were used, consisting of 16 noncrushed fresh, 136 crushed fresh, 8 noncrushed preserved, and 117 crushed preserved. Graft success rate was 93.8% for noncrushed fresh cartilage grafts, 87.5% for crushed fresh, 87.5% for noncrushed preserved, and 85.5% for crushed preserved graft. We conclude that preserved autogenous cartilage retains almost as much graft volume as fresh cartilage in rhinoplasties and eliminates the need for harvesting a graft. Cartilage removed during nasal surgery, particularly when a septoplasty is being performed, is valuable and should be stored for possible later use.

Adult↗

PubMed1994

Anaesthesia for abdominal vascular surgery in patients with coronary artery disease (CAD), Part I: Isoflurane produces dose-dependent coronary vasodilation.

The effects of anaesthesia for major abdominal vascular surgery on coronary flow regulation and mechanisms of myocardial ischaemia were studied in 56 patients with CAD, using a randomized, partly double-blinded protocol. After induction with fentanyl (3 micrograms.kg-1) and thiopentone (2-4 mg.kg-1) and tracheal intubation, principal anaesthetics were nitrous oxide/oxygen (60/40) with isoflurane (n = 20), halothane (n = 19) or fentanyl (15-20 micrograms.kg-1) (n = 17). Conventional invasive techniques and coronary venous retrograde thermodilution were used to assess systemic and coronary haemodynamics. Coronary vascular resistance was estimated from myocardial oxygen extraction. Myocardial ischaemia was diagnosed by 12-lead ECG and/or anterior wall motion abnormalities by cardiokymography and/or myocardial lactate production. When adjustment of anaesthetic dose was insufficient for haemodynamic control, i.v. phenylephrine and nitroglycerine were administered to treat hypotension and hypertension or cardiac failure respectively. Measurements were performed at four specific intervals; awake, before surgery and 10 and 30 min after abdominal incision. Comparable changes of systemic haemodynamics and myocardial oxygen consumption were observed in the three groups. Coronary vasodilation was evidenced in isoflurane patients only and was linearly dose-dependent (P < 0.001). Partial Least Squares Projections to Latent Structures modelling with cross validation confirmed this dose-dependency and ruled out a clinically measurable influence by intervention drugs or simultaneous systemic haemodynamic abnormalities. The incidence of myocardial ischaemia during anaesthesia and surgery was comparable in the three groups (35, 37 and 24%, respectively) and there was an association with systemic haemodynamic aberrations in 19 of the 27 ischaemic episodes. In contrast to ischaemic halothane and fentanyl patients, isoflurane patients with ischaemia had significantly lower myocardial oxygen extraction (P = 0.008 and P = 0.001, respectively), indicating that the oxygen extraction reserve was not utilized in a normal way during ischaemia.

Abdomen↗

PubMed1994

Anaesthesia for abdominal aortic surgery in patients with coronary artery disease, Part II: Effects of nitrous oxide on systemic and coronary haemodynamics, regional ventricular function and incidence of myocardial ischaemia.

This study examines the effects of nitrous oxide on haemodynamics, anterior left ventricular (LV) function and incidence of myocardial ischaemia in abdominal vascular surgical patients with coronary artery disease. Forty-seven patients were randomly assigned to isoflurane-fentanyl anaesthesia with nitrous oxide-oxygen vs air-oxygen (control). Systemic and coronary haemodynamics, 12-lead ECG, LV anterior wall motion by cardiokymography (CKG) and myocardial lactate balance were recorded at four intervals: before and during anaesthesia and 10 and 30 minutes into surgery. Systemic haemodynamics were controlled by anaesthetic dose, and, when insufficient, by i.v. nitroglycerine (NG) in case of LV failure (PCWP > 18 mmHg) and by phenylephrine during hypotension. We found that nitrous oxide was associated with greater need for i.v. nitroglycerin (patients: P = 0.031, episodes P = 0.005) and more myocardial ischaemia (patients P = 0.012, episodes P = 0.001) despite systemic and coronary haemodynamics comparable to the control group. We conclude that nitrous oxide, known to have both sympathomimetic and cardiodepressive actions, produced cardiodepression in the face of sympathetic stimulation. Our study design did not allow to conclude if myocardial ischaemia was the consequence of increased wall stress or a reason for the observed LV dysfunction. The higher incidence of introperative myocardial ischaemia and need for NG did not cause increased cardiac morbidity.

Abdomen↗

PubMed1994

Old-onset Parkinson's disease compared with young-onset disease: clinical differences and similarities.

Of 261 patients with clinically diagnosed Parkinson's disease (PD), whose age at the onset was 58.2 +/- 11.3, 46 patients with the onset age above 70 (the mean for the whole group + 1SD) were compared to 44 patients with onset age below 47 (the mean for the whole group - 1 SD). Old-onset PD patient were more susceptible to develop psychotic complications of levodopa treatment. More often had they tremor both as presenting and dominant symptom of their disease. Among young-onset PD bradykinesia was more often the dominant clinical feature, and susceptibility to levodopa induced dyskinesia was higher. In 9 cases of young-onset PD (20.5% of this group) paraesthesia was a presenting symptom, compared to only 1 patient (2%) in the group of old-onset PD.

Activities of Daily Living↗

PubMed1994

Oral tolerance: immunologic mechanisms and treatment of animal and human organ-specific autoimmune diseases by oral administration of autoantigens.

Oral tolerance is a long recognized method to induce peripheral immune tolerance. The primary mechanisms by which orally administered antigen induces tolerance are via the generation of active suppression or clonal anergy. Low doses of orally administered antigen favor active suppression whereas higher doses favor clonal anergy. The regulatory cells that mediate active suppression act via the secretion of suppressive cytokines such as TGF beta and IL-4 after being triggered by the oral tolerogen. Furthermore, antigen that stimulates the gut-associated lymphoid tissue preferentially generates a Th2 type response. Because the regulatory cells generated following oral tolerization are triggered in an antigen-specific fashion but suppress in an antigen nonspecific fashion, they mediate "bystander suppression" when they encounter the fed autoantigen at the target organ. Thus it may not be necessary to identify the target autoantigen to suppress an organ-specific autoimmune disease via oral tolerance; it is necessary only to administer orally a protein capable of inducing regulatory cells that secrete suppressive cytokines. Orally administered autoantigens suppress several experimental autoimmune models in a disease- and antigen-specific fashion; the diseases include experimental autoimmune encephalomyelitis (EAE), uveitis, and myasthenia, collagen- and adjuvant-induced arthritis, and diabetes in the NOD mouse. In addition, orally administered alloantigen suppresses alloreactivity and prolongs graft survival. Initial clinical trials of oral tolerance in multiple sclerosis, rheumatoid arthritis, and uveitis have demonstrated positive clinical effects with no apparent toxicity and decreases in T cell autoreactivity.

Administration, Oral↗

PubMed1994

Distress, denial, and low adherence to behavioral interventions predict faster disease progression in gay men infected with human immunodeficiency virus.

This study examined psychological prediction of 2-year disease progression in gay men after finding out their human immunodeficiency virus (HIV) serostatus. Psychological and immune status of asymptomatic gay men who did not know their HIV serostatus was monitored during the 5 weeks before and after serostatus notification. The men were randomly assigned to an exercise. cognitive-behavioral stress-management intervention, or control group. At 2-year follow-up for the 23 men who turned out to be seropositive. 9 had developed symptoms, including 5 with acquired immune deficiency syndrome--4 of whom died. Distress at diagnosis, denial (5 weeks post-diagnosis minus pre-diagnosis). and low adherence during interventions were significant predictors of 2-year disease progression. Denial and adherence remained significant predictors of disease progression even after controlling for CD4 number at entry. Furthermore. change in denial was significantly correlated with immune status 1 year later; l-year immune status was significantly correlated with 2-year disease progression. The present study therefore demonstrates significant relations between psychological variables on the one hand and both immune measures and HIV-1 disease progression on the other. We conclude that distress, denial, and low protocol compliance predict subsequent disease progression.

Journal Article↗

PubMed1994

The effect of varying levels of dietary vitamin A on immune response in the chick.

The effect of dietary vitamin A on antibody production and T cell proliferative response was determined in broilers from 21 to 39 d old. Chicks were fed soybean meal-sorghum diets with levels of supplemented vitamin A from 0 to 13,200 micrograms/kg retinol equivalents from hatching and were immunized with beta-casein at 21 d of age. T cell proliferation response to beta-casein or an acetone precipitate of antigen to Mycobacterium tuberculosis was determined in vitro at 34 to 37 d old. Antibodies to beta-casein in serum were determined every 5 d from 21 d of age. In chicks with no added dietary vitamin A, antibody production and proliferative response were depressed in comparison with chicks receiving vitamin A. Addition of small amounts of vitamin A enhanced the responses; both antibody production and proliferative responses increased with dietary vitamin A until the diet contained 6,660 micrograms/kg, above which the responses decreased. This suggests that maximal immune responses in the chick may be achieved at dietary intakes considerably higher than NRC recommendations.

Animal Feed↗

PubMed1994

Effects of distance between objects and distance from the vertical axis on shape identity judgments.

In three experiments, we independently manipulated the angular disparity between objects to be compared and the angular distance between the central axis of the objects and the vertical axis in a mental rotation paradigm. There was a linear increase in reaction times that was attributable to both factors. This result held whether the objects were rotated (with respect to each other and to the upright) within the frontal-parallel plane (Experiment 1) or in depth (Experiment 2), although the effects of both factors were greater for objects rotated in depth than for objects rotated within the frontal-parallel plane (Experiment 3). In addition, the factors interacted when the subjects had to search for matching ends of the figures (Experiments 1 and 2), but they were additive when the ends that matched were evident (Experiment 3). These data may be interpreted to mean that subjects normalize or reference an object with respect to the vertical upright as well as compute the rotational transformations used to determine shape identity.

Adult↗

PubMed1994

Shape discriminations of three-dimensional objects depend on the number and location of bends.

In three experiments, subjects made shape discriminations of three-dimensional objects differing in orientation, number of bends, and location of bends (e.g., the central arm vs. a minor subarm). In general of bends, but only after a certain threshold of bends in the objects had been reached (Experiment 1). This effect was not due to the subjects' having to search for matching ends of the objects (Experiment 2). In contrast, rotation rates were influenced by the location of the bends, but not by the number of bends per se (Experiment 3). The results support a representational scheme that is hierarchical, but not necessarily one in which the principal axis of an object is paramount.

Depth Perception↗

PubMed1994

MR and positron emission tomography in the diagnosis of surgically correctable temporal lobe epilepsy.

PURPOSE: To determine the association of an MR abnormality and a positron emission tomography (PET) abnormality with a good outcome in patients with temporal lobe epilepsy after lobectomy, the association of combined PET and MR findings with good outcomes after lobectomy, and MR and PET pathologic correlation. METHODS: MR and PET were performed on 27 patients in a blinded study. Histologic studies were correlated with foci of increased T2 signal. RESULTS: Increased signal or decreased volume of the hippocampus was noted in 13 of 15 patients with mesial temporal sclerosis. Twelve of 15 had positive PET findings. MR identified 20 (83%) of the 24 patients with good outcomes. PET identified 71%. When MR and PET were combined, they detected 95% of the patients with good outcome. Region of interest measurements of the hippocampus in 11 study patients and 7 control subjects documented a significant increase in signal in the patients with seizures. Histologic correlative studies demonstrated that increased T2 signals related to astrocytosis in the hippocampus and adjacent white matter. CONCLUSIONS: MR (increased signal and decreased volume of the hippocampus) significantly improved the capability to identify those persons who would be helped by lobectomy. MR sensitivity exceeded that of PET.

Adolescent↗