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Biomedical subjects

A Friedman

Publications and source records attributed to A Friedman.

At least 73 records · Page 4Linked to original sources
PubMed1998

Delayed auditory feedback during smoking cessation.

Delays between speech production and hearing, delayed auditory feedback (DAF), reduce speech and reading rates. Smoking cessation in heavy smokers causes subjective reports of difficulty in concentration, decrements in cognitive performance, and EEG changes. The purpose of the present study was to determine if tobacco cessation disrupts linguistic processing as modeled by the DAF paradigm. Smokers (n = 14) were tested on 3 d of ad libitum smoking and 3 d no smoking. At each session, they read a word list (24 words) and a story (about 57 words) with and without delay (220 msec). The delay significantly decreased reading speed of the story from 3.4 to 2.9 words per second (wps) and of list from 2.1 to 1.7 wps. However, tobacco cessation had no significant effect on reading speed and no interaction with DAF. Although tobacco withdrawal slows performance on cognitive tasks, linguistic processing modeled by DAF is preserved. DAF may prove useful for the study of other drug classes and drug withdrawal states.

Adult↗
PubMed1998

Analysis of DNA mismatch repair proteins in human medulloblastoma.

During replication, the primary function of the eukaryotic DNA mismatch repair (MMR) system is to recognize and correct mismatched base pairs within the DNA helix. Deficiencies in MMR have been reported previously in cases of hereditary nonpolyposis colorectal cancer and sporadic tumors occurring in a variety of tissues including gliomas. Furthermore, recent evidence indicates that the MMR system may be involved in mediating therapeutic sensitivity to alkylating agents. In this study, 22 neoplastic tissue samples from 22 patients who underwent surgical resection for medulloblastoma, a common cerebellar tumor of childhood, were assayed for the presence or absence of MMR polypeptides using Western blot and immunohistochemical techniques. Results from these experiments indicate that the MMR system is not commonly deficient in medulloblastoma.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Acetylcholinesterase-transgenic mice display embryonic modulations in spinal cord choline acetyltransferase and neurexin Ibeta gene expression followed by late-onset neuromotor deterioration.

To explore the possibility that overproduction of neuronal acetylcholinesterase (AChE) confers changes in both cholinergic and morphogenic intercellular interactions, we studied developmental responses to neuronal AChE overexpression in motoneurons and neuromuscular junctions of AChE-transgenic mice. Perikarya of spinal cord motoneurons were consistently enlarged from embryonic through adult stages in AChE-transgenic mice. Atypical motoneuron development was accompanied by premature enhancement in the embryonic spinal cord expression of choline acetyltransferase mRNA, encoding the acetylcholine-synthesizing enzyme choline acetyltransferase. In contrast, the mRNA encoding for neurexin-Ibeta, the heterophilic ligand of the AChE-homologous neuronal cell surface protein neuroligin, was drastically lower in embryonic transgenic spinal cord than in controls. Postnatal cessation of these dual transcriptional responses was followed by late-onset deterioration in neuromotor performance that was associated with gross aberrations in neuromuscular ultrastructure and with pronounced amyotrophy. These findings demonstrate embryonic feedback mechanisms to neuronal AChE overexpression that are attributable to both cholinergic and cell-cell interaction pathways, suggesting that embryonic neurexin Ibeta expression is concerted in vivo with AChE levels and indicating that postnatal changes in neuronal AChE-associated proteins may be involved in late-onset neuromotor pathologies.

Acetylcholinesterase↗
PubMed1997

Further protection against antigenic drift of influenza virus in a ferret model by DNA vaccination.

Previously we showed that immunization of ferrets with DNA encoding the hemagglutinin (HA), nucleoprotein (NP), and matrix protein (M1) of influenza virus induced protective immune responses. A DNA vaccine encoding HA (from a 1991 strain), NP and M1 (from a 1989 strain) protected ferrets better against challenge with the antigenic drift variant A/Georgia/03/93 than did the inactivated vaccine from the 1992-93 influenza season. Here we report that the same DNA vaccine protected ferrets against a second, further divergent, drift variant (A/Johannesburg/33/94). Furthermore, the extent of protection provided by the DNA vaccine was equivalent to the homologous protection provided by an inactivated vaccine that exactly matched the challenge strain.

Animals↗
PubMed1997

Effect of vitamin A on the oxidative stability of broiler meat during storage: lack of interactions with vitamin E.

1. An experiment was carried out with male broiler chicks to evaluate the combined effect of two concentrations of vitamin A (1.032 and 10.32 mg retinyl acetate/kg diet) and two concentrations of vitamin E (0 and 150 mg alpha-tocopheryl acetate/kg diet) on the oxidative stability of the drumstick meat of broiler chickens. The experimental diets were fed from 1 to 42 d of age. The oxidative stability, evaluated by thiobarbituric acid reactive substances (TBARS) values, was determined after 125 d of storage at -18 degrees C. 2. TBARS values were very low and not significantly affected by dietary vitamins A and E or their combinations. However, the TBARS values in the meat of birds fed on the vitamin E-free diets, but not on the vitamin E-supplemented diets, were markedly increased after using an accelerated test of oxidation of the meat lipids by incubation. This resulted in a significant (P<0.001) difference from vitamin E supplementation. Vitamin A, alone or in combination with vitamin E, did not affect TBARS values found after incubation. 3. It is concluded that vitamin A at the concentrations used had no effect on the oxidative stability of the meat, in contrast to the protective effect of vitamin E, and that there is no interaction between the effect of these two vitamins on meat stability.

Animal Feed↗
PubMed1997

Effect of dietary fatty acids on humoral immune response of turkeys.

1. This study examined the effect of increasing amounts of dietary polyunsaturated fatty acids on the fatty acid composition in serum and antibody production following a standard vaccination programme in growing turkeys. Turkey poults were fed on 5 diets containing 75g/kg added fat made up of different proportions of palm and soyabean oils, and were vaccinated against Newcastle disease, infectious bronchitis and necrotic enteritis according to a standard vaccination programme. Blood samples were taken before and one week after each vaccination. 2. Fatty acid composition in serum reflected the composition of the diets although arachidonic acid concentration was not changed by dietary fatty acid content. Growth, erythrocyte and leukocyte parameters were not affected by the respective diets. 3. Specific antibody production was related quadratically to serum linoleic and total n-6 polyunsaturated fatty acid concentrations. No correlation was found with linolenic or arachidonic acids. 4. It is concluded that dietary fatty acid composition can augment the specific anti-vaccine immune response in turkey poults.

Animal Feed↗
PubMed1997

Protective cellular immunity: cytotoxic T-lymphocyte responses against dominant and recessive epitopes of influenza virus nucleoprotein induced by DNA immunization.

DNA immunization offers a novel means to induce cellular immunity in a population with a heterogeneous genetic background. An immunorecessive cytotoxic T-lymphocyte (CTL) epitope in influenza virus nucleoprotein (NP), residues 218 to 226, was identified when mice were immunized with a plasmid DNA encoding a full-length mutant NP in which the anchor residues for the immunodominant NP147-155 epitope were altered. Mice immunized with wild-type or mutant NP DNA were protected from lethal cross-strain virus challenge, and the protection could be adoptively transferred by immune splenocytes, indicating the role of cell-mediated immunity in the protection. DNA immunization is capable of eliciting protective cellular immunity against both immunodominant and immunorecessive CTL epitopes in the hierarchy seen with virus infection.

Animals↗
PubMed1997

Sex hormones and renal nitric oxide synthases.

The present study was undertaken to determine whether sex hormones influence nitric oxide synthase levels in the kidney. Five groups of rats were studied: males, castrated males, females, oophorectomized females, and oophorectomized females receiving estradiol replacement therapy. Endothelial nitric oxide synthase (eNOS) levels in the kidney were measured by Western blotting. eNOS levels were significantly greater in the renal medulla of female rats compared with male rats (3545 +/- 473 versus 2418 +/- 205 densitometry units (DU), P < 0.05). Oophorectomy reduced renal medullary eNOS levels to that of intact male rats (2566 +/- 304 DU, P = NS). Estrogen replacement therapy significantly increased medullary eNOS levels in oophorectomized animals (3249 +/- 377 versus 2302 +/- 213 DU, P < 0.05). Renal inducible nitric oxide synthase (iNOS) levels were measured after induction with lipopolysaccharide. iNOS levels were significantly greater in the renal medulla of female rats compared with male rats (677 +/- 253 versus 252 +/- 12 DU, P < 0.05). Oophorectomy reduced renal medullary iNOS levels to that of intact male rats (295 +/- 57 DU, P = NS). In contrast, estrogen replacement therapy significantly increased medullary iNOS levels in oophorectomized animals (682 +/- 356 versus 160 +/- 92 DU, P < 0.05). Steady-state levels of mRNA for iNOS were found to be higher in the inner medulla of female rats compared with male rats (1519 +/- 211 versus 899 +/- 105 DU, P < 0.05). In contrast to these findings, sex hormones failed to influence nitric oxide production or iNOS levels in lipopolysaccharide-stimulated mesangial cells in culture. These results suggest that gender may influence renal medullary synthesis of nitric oxide.

Animals↗
PubMed1997

Controversies about iron in parkinsonian and control substantia nigra.

According to the oxidative stress theory iron may play an important role in the pathogenesis of neurodegenerative diseases, as e.g. Parkinson's disease (PD). This review presents the results of studies, obtained by various methods, of iron in substantia nigra (SN)--a cerebral structure which degenerates in PD--and shows controversies concerning the amount of iron, its redox state, and the iron binding compounds. Taking into account all published experimental results, the increase in the concentration of iron in parkinsonian SN vs. control may be estimated as (3 +/- 5)%. The presence of large amounts of divalent iron in post mortem SN can be unequivocally negated. It is, however, still possible that iron is involved in the pathogenesis of PD, as even minor changes in the amount and form of iron may initiate processes leading to cells death.

Humans↗
PubMed1997

Priming of cytotoxic T lymphocytes by DNA vaccines: requirement for professional antigen presenting cells and evidence for antigen transfer from myocytes.

BACKGROUND: MHC class I molecule-restricted cytotoxic T-lymphocyte (CTL) responses are induced following either intramuscular (i.m.) injection of a DNA plasmid encoding influenza virus nucleoprotein (NP) or transplantation of myoblasts stably transfected with the NP gene, the latter indicating that synthesis of NP by myocytes in vivo is sufficient to induce CTL. The present study was designed to investigate the role of muscle cells and involvement of professional antigen-presenting cells (APCs) in priming CTL responses following DNA vaccination. MATERIALS AND METHODS: Parent-->F1 bone marrow (BM) chimeric mice were generated whose somatic cells include muscle cells bearing both parental MHC haplotypes, while their professional APCs express only the donor MHC haplotypes. RESULTS AND CONCLUSIONS: Upon injection of NP DNA, or after infection with influenza virus, CTL responses generated in the chimeras were restricted to the donor MHC haplotype. Thus cells of BM lineage were definitively shown to be responsible for priming such CTL responses after infection or DNA immunization. Moreover, expression of antigen by muscle cells in BM chimeric mice after myoblast transplantation is sufficient to induce CTL restricted only by the MHC haplotype of the donor BM. This indicates that transfer of antigen from myocytes to professional APCs can occur, thus obviating a requirement for direct transfection of BM-derived cells.

Animals↗
PubMed1997

Collagen subtype pattern in normal and varicose saphenous veins in humans.

Our present study was to determine the collagen subtype pattern in the greater saphenous vein of the lower limb, obtained from 21 normal (macroscopically and ultrastructurally non-varicose vein segments from non-varicose subjects) and 37 varicose subjects, and to compare affected (macroscopically and ultrastructurally varicose segments from varicose veins) vs. non-affected (macroscopically and ultrastructurally non-varicose segments from varicose veins) segments (16). After elastase pretreatment and partial pepsin digestion, types I, III & V collagens (CI, CIII, CV) were extracted selectively by differential salt precipitation and measured quantitatively in samples obtained from normal and varicose saphenous veins-either affected or unaffected segments. Significant elevations of water (p < 0.05) and collagen type I [CI] (p < 0.01) content in varicose veins (both affected and unaffected segments) as compared with normal saphenous veins were observed. The collagen type III (CIII) and collagen type V (CV) content of varicose veins were found to be slightly reduced as compared to normal veins and consequently the CI/(CIII+CV) ratio in varicose veins increased significantly (p < 0.02) as compared to normal veins. Elevation of the CI/(CIII+CV) ratio in varicose veins may cause considerable weakening of the venous wall, further supporting the "weak wall" theory of varicose vein etiology.

Case-Control Studies↗
PubMed1997

Induction of immunity by DNA vaccination: application to influenza and tuberculosis.

DNA vaccination is an effective means of inducing both humoral and cell-mediated immunity in animal models of infectious disease. Presented here are data generated in two distinct disease models; one viral (influenza) and one bacterial (tuberculosis). Specifically, plasmid DNA encoding an influenza virus antigen (nucleoprotein; NP) and a Mycobacterium tuberculosis antigen (antigen 85; Ag85) were prepared and tested as DNA vaccines in mice. In both cases, high titer antibody responses and robust cell-mediated immune responses were induced against the respective antigens. With respect to the latter, lymphocyte proliferation, Th1-type cytokine secretion, and cytotoxic T lymphocyte responses were observed upon restimulation with antigen in vitro. Furthermore, protective efficacy in animal challenge models was demonstrated in both systems. The data support the hypothesis that DNA vaccination will prove to be a broadly applicable technique for inducing immunity against various infectious diseases.

Animals↗
PubMed1996

Slow inactivation of Na+ current and slow cumulative spike adaptation in mouse and guinea-pig neocortical neurones in slices.

1. Spike adaptation of neocortical pyramidal neurones was studied with sharp electrode recordings in slices of guinea-pig parietal cortex and whole-cell patch recordings of mouse somatosensory cortex. Repetitive intracellular stimulation with 1 s depolarizing pulses delivered at intervals of < 5 s caused slow, cumulative adaptation of spike firing, which was not associated with a change in resting conductance, and which persisted when Co2+ replaced Ca2+ in the bathing medium. 2. Development of slow cumulative adaptation was associated with a gradual decrease in maximal rates of rise of action potentials, a slowing in the post-spike depolarization towards threshold, and a positive shift in the threshold voltage for the next spike in the train; maximal spike repolarization rates and after-hyperpolarizations were unchanged. 3. The data suggested that slow adaptation reflects use-dependent removal of Na+ channels from the available pool by an inactivation process which is much slower than fast, Hodgkin-Huxley-type inactivation. 4. We therefore studied the properties of Na+ channels in layer II-III mouse neocortical cells using the cell-attached configuration of the patch-in-slice technique. These had a slope conductance of 18 +/- 1 pS and an extrapolated reversal potential of 127 +/- 6 mV above resting potential (Vr) (mean +/- S.E.M.; n = 5). Vr was estimated at -72 +/- 3 mV (n = 8), based on the voltage dependence of the steady-state inactivation (h infinity) curve. 5. Slow inactivation (SI) of Na+ channels had a mono-exponential onset with tau on between 0.86 and 2.33 s (n = 3). Steady-state SI was half-maximal at -43.8 mV and had a slope of 14.4 mV (e-fold)-1. Recovery from a 2 s conditioning pulse was bi-exponential and voltage dependent; the slow time constant ranged between 0.45 and 2.5 s at voltages between-128 and -68 mV. 6. The experimentally determined parameters of SI were adequate to simulate slow cumulative adaptation of spike firing in a single-compartment computer model. 7. Persistent Na+ current, which was recorded in whole-cell configuration during slow voltage ramps (35 mV s-1), also underwent pronounced SI, which was apparent when the ramp was preceded by a prolonged depolarizing pulse.

Action Potentials↗
PubMed1996

A phase III randomized prospective trial of external beam radiotherapy, mitomycin C, carmustine, and 6-mercaptopurine for the treatment of adults with anaplastic glioma of the brain. CNS Cancer Consortium.

PURPOSE: This study was designed to evaluate strategies to overcome the resistance of anaplastic gliomas of the brain to external beam radiotherapy (ERT) plus carmustine (BCNU). Patients were > or = 15 years of age, had a histologic diagnosis of malignant glioma, and a Karnofsky performance status (KPS) > or = 60%. METHODS AND MATERIALS: In Randomization 1, patients were assigned to receive either ERT alone (61.2 Gy) or ERT plus mitomycin C (Mito, IV 12.5 mg/m(2)) during the first and fourth week of ERT. After this treatment, patients went on to Randomization 2, where they were assigned to receive either BCNU (i.v. 200 mg/m(2)) given at 6-week intervals or 6-mercaptopurine (6- MP, 750 mg/m(2) IV daily for 3 days every six weeks), with BCNU given on the third day of the 6-MP treatment. Three hundred twenty-seven patients underwent Randomization 1. One hundred sixty-four received ERT alone, and 163 received ERT + Mito [average 52.7 years; 63% male; 69% glioblastoma multiforme (GBM); 66% had a resection; 56% KPS > or = 90%]. Step-wise analysis of survival from Randomization 1 or 2 indicates that survival was significantly diminished by: (a) age > or = 45 years (b) KPS < 90%; (c) GBM/gliosarcoma histology; (d) stereotactic biopsy as opposed to open biopsy or resection. Median survival from Randomization 1 in both arms (ERT + Mito) was 10.8 months. Median survival from Randomization 2 was 9.3 months for BCNU/6MP vs. 11.4 months for the BCNU group (p = 0.35). Carmustine/6-MP showed a possible survival benefit for histologies other than GBM/GS. Two hundred and thirty-three patients underwent Randomization 2. The proportion of patients in the ERT group who terminated study prior to Randomization 2 was significantly less in the ERT group than in the ERT + Mito group (20 vs. 37%, p < 0.001). CONCLUSIONS: (a) The addition of Mito to ERT had no impact on survival; (b) patients treated with ERT + Mito were at greater risk of terminating therapy prior to Randomization 2; (c) there was not a significant survival benefit to the addition of 6-MP to BCNU.

Adult↗
PubMed1996

Induction of anergy in Th1 lymphocytes by oral tolerance. Importance of antigen dosage and frequency of feeding.

Oral tolerance, a biologically relevant pathway for inducing peripheral tolerance in T lymphocytes, occurs by two distinct mechanisms. Multiple low doses of antigen induce regulatory T lymphocytes that secrete immunosuppressive cytokines, whereas feeding a single high dose of antigen induces anergy of antigen-specific Th1 lymphocytes (diminished IgG2a, IL-2, and IFNgamma) with intact Th2 responses (IgG1 and IL-4). Anergy was demonstrated by the ability to reverse tolerant state after culturing tolerant cells in rIL-2. Reversal of the tolerant state was established in vitro by increase in frequency of IL-2 secreting cells, and in vivo by specific IgG2a production in irradiated mice adoptively transferred with cells cultured in rIL-2. Inasmuch as the induction of anergy was inhibited by the presence of antibodies specific for the tolerizing antigen, it appears that the oral induction of anergy might depend on the systemic dissemination of antigen (or its fragments) absorbed from the gut. It is suggested that tolerance is insured by the fact that this absorbed antigen is presented to Th1 lymphocytes in draining lymph nodes in the absence of inflammatory and costimulatory molecules.

Administration, Oral↗