Search PubMed⌕ Search

Biomedical subjects

A Friedman

Publications and source records attributed to A Friedman.

At least 55 records · Page 3Linked to original sources
PubMed1999

Dose dependence of CTL precursor frequency induced by a DNA vaccine and correlation with protective immunity against influenza virus challenge.

Intramuscular injection of BALB/c mice with a DNA plasmid encoding nucleoprotein (NP) from influenza virus A/PR/8/34 (H1N1) provides cross-strain protection against lethal challenge with influenza virus A/HK/68 (H3N2). CTL specific for the H-2Kd-restricted epitope NP147-155 are present in these mice and are thought to play a role in the protection. To assess the effectiveness of NP DNA immunization in comparison with influenza virus infection in the induction of CTL responses, we monitored the frequency of CTL precursors (CTLp) in mice following i.m. injection with NP DNA or intranasal infection with influenza virus and showed that the CTLp frequency in NP DNA-immunized mice can reach levels found in mice that had been infected with influenza virus. We also measured the CTLp frequency, anti-NP Ab titers, and T cell proliferative responses in mice that were injected with titrated dosages of NP DNA and documented a correlation of the CTLp frequency and the Ab titers, but not proliferative responses, with the injection dose. Furthermore, we observed a positive correlation between the frequency of NP147-155 epitope-specific CTLp and the extent of protective immunity against cross-strain influenza challenge induced by NP DNA injection. Collectively, these results and our early observations from adoptive transfer experiments of in vitro activated lymphocytes from NP DNA-immunized mice suggest a protective function of NP-specific CTLp in mice against cross-strain influenza virus challenge.

Animals↗
PubMed1999

A-protein from achromogenic atypical Aeromonas salmonicida: molecular cloning, expression, purification, and characterization.

Achromogenic atypical Aeromonas salmonicida is the causative agent of goldfish ulcer disease. Virulence of this bacterium is associated with the production of a paracrystalline outer membrane A-layer protein. The species-specific structural gene for the monomeric form of A-protein was cloned into a pET-3d plasmid in order to express and produce a recombinant form of the protein in Escherichia coli BL21(DE3). The induced protein was isolated from inclusion bodies by a simple solubilization-renaturation procedure and purified by ion exchange chromatography on Q-Sepharose to over 95% pure monomeric protein. Recombinant A-protein was compared by biochemical, immunological, and molecular methods with the A-protein isolated from atypical A. salmonicida bacterial cells by the glycine and the membrane extraction methods. The recombinant form was found to be undistinguishable from the wild type when examined by SDS-PAGE and gel filtration chromatography. The immunological similarity of the protein samples was demonstrated by employing polyclonal and monoclonal antibodies in ELISA and Western blot techniques. All forms of A-protein were found to activate the secretion of tumor necrosis factor alpha from murine macrophage. To date, this represents the first large-scale production of biologically active recombinant A-protein.

Aeromonas↗
PubMed1999

Analysis of a mathematical model for the growth of tumors.

In this paper we study a recently proposed model for the growth of a nonnecrotic, vascularized tumor. The model is in the form of a free-boundary problem whereby the tumor grows (or shrinks) due to cell proliferation or death according to the level of a diffusing nutrient concentration. The tumor is assumed to be spherically symmetric, and its boundary is an unknown function r = s(t). We concentrate on the case where at the boundary of the tumor the birth rate of cells exceeds their death rate, a necessary condition for the existence of a unique stationary solution with radius r = R0 (which depends on the various parameters of the problem). Denoting by c the quotient of the diffusion time scale to the tumor doubling time scale, so that c is small, we rigorously prove that (i) lim inf s(t) > 0, i.e. once engendered, tumors persist in time. t-->infinity Indeed, we further show that (ii) If c is sufficiently small then s(t)-->R0 exponentially fast as t-->infinity, i.e. the steady state solution is globally asymptotically stable. Further, (iii) If c is not "sufficiently small" but is smaller than some constant gamma determined explicitly by the parameters of the problem, then t-->infinity lim sup s(t) < infinity; if however c is "somewhat" larger than gamma then generally s(t) does not remain bounded and, in fact, s(t)-->infinity exponentially fast as t-->infinity.

Models, Biological↗
PubMed1999

Effect of repeated doses of sucrose during heel stick procedure in preterm neonates.

The purpose of this randomized clinical trial was to test the efficacy of repeated versus single dose sucrose to decrease pain from routine heel stick procedures in preterm neonates. Infants (n = 48) in the first week of life with a mean gestational age of 31 weeks received 0.05 ml of 24% sucrose solution or sterile water by mouth (1) 2 min prior to actual lancing of the heel; (2) just prior to lancing, and (3) 2 min after lancing. The single-dose group received sucrose for the first dose and water for the second and third dose; the repeated-dose group received sucrose three times, and the placebo group received only water. The Premature Infant Pain Profile (PIPP) scores were obtained for five 30-second blocks from lancing. Both sucrose groups had lower PIPP scores (single sucrose pain scores, 6.8-8.2, p = 0.07; repeated sucrose pain scores, 5.3-6. 2, p < 0.01) than water (pain scores 7.9-9.1), and in the last block, the repeated dose had lower scores than the single dose (6.2 vs. 8. 2, p < 0.05).

Analgesics↗
PubMed1999

Intraovarian regulation of luteolysis.

The corpus luteum is a transient gland, which is only functional for 17-18 days in the cyclic cow or for up to 200 days in the pregnant cow. Regression of the corpus luteum is essential for normal cyclicity as it allows the development of a new ovulatory follicle, whereas prevention of luteolysis is necessary for the maintenance of pregnancy. Evidence acquired over the past three decades indicated that PGF2 alpha is the luteolytic hormone in ruminants. Nevertheless, the detailed mechanisms of PGF2 alpha action are just beginning to be clarified. A pivotal role for an endothelial cell product endothelin 1 (ET-1) has been documented in PGF2 alpha-induced luteal regression. ET-1 inhibited progesterone production by luteal cells in a dose-dependent manner via selective ET-1 binding sites (ETA). The inhibitory action of PGF2 alpha on progesterone secretion (in vivo and in vitro) was blocked by a selective ETA receptor antagonist. This implied that ET-1 (through ETA receptors present on steroidogenic cells) may have mediated the inhibitory effect of PGF2 alpha. The involvement of ET-1 in luteal regression was also suggested by the observation that the highest concentrations of ET-1 coincide with uterine PGF2 alpha surges. Furthermore, PGF2 alpha administration upregulated ET-1 expression within the corpus luteum. Later stages of luteal regression, which involve programmed cell death (PCD), are presumably mediated by immune cells. ET-1 may also be involved in this process by promoting leukocyte migration and stimulating macrophages to release tumour necrosis factor alpha (TNF alpha). The TNF alpha receptor type 1 (p55) is present on luteal cells (endothelial and steroidogenic cells) and could initiate PCD and the structural demise of the corpus luteum.

Animals↗
PubMed1999

[Treatment of Parkinson's disease--from theory to practice].

The symptomatic treatment of Parkinson's disease is based on assumption that its symptoms are a consequence of damage to the dopaminergic system at the level of substantia nigra. However, not all symptoms can be explained by this damage, moreover, substitution therapy /with preparations containing dopamine precursor--levodopa and agonists of the dopaminergic receptor /not only fails to remove all disease symptoms but can even produce adverse effects. Theoretical bases of treatment are discussed, including the non-motor signs /dementia, depression, autonomic system disturbances/ with the analysis of how these theoretical assumptions come true in practise, including the author's practice. a schema is proposed of diagnosis establishing and decision taking of treatment with stress laid on the most frequent diagnostic and therapeutic errors. Expectations and hopes are discussed also concerning the search for the cause and better therapeutic methods in the future.

Animals↗
PubMed1998

Acute stress facilitates long-lasting changes in cholinergic gene expression.

Acute traumatic stress may lead to post-traumatic stress disorder (PTSD), which is characterized by delayed neuropsychiatric symptoms including depression, irritability, and impaired cognitive performance. Curiously, inhibitors of the acetylcholine-hydrolysing enzyme acetylcholinesterase may induce psychopathologies that are reminiscent of PTSD. It is unknown how a single stressful event mediates long-term neuronal plasticity. Moreover, no mechanism has been proposed to explain the convergent neuropsychological outcomes of stress and of acetylcholinesterase inhibition. However, acute stress elicits a transient increase in the amounts released of the neurotransmitter acetylcholine and a phase of enhanced neuronal excitability. Inhibitors of acetylcholinesterase also promote enhanced electrical brain activity, presumably by increasing the survival of acetylcholine at the synapse. Here we report that there is similar bidirectional modulation of genes that regulate acetylcholine availability after stress and blockade of acetylcholinesterase. These calcium-dependent changes in gene expression coincide with phases of rapid enhancement and delayed depression of neuronal excitability. Both of these phases are mediated by muscarinic acetylcholine receptors. Our results suggest a model in which robust cholinergic stimulation triggers rapid induction of the gene encoding the transcription factor c-Fos. This protein then mediates selective regulatory effects on the long-lasting activities of genes involved in acetylcholine metabolism.

Acetylcholine↗
PubMed1998

Induction of MHC class I-restricted CTL response by DNA immunization with ubiquitin-influenza virus nucleoprotein fusion antigens.

DNA vaccines have been shown to be an effective means of inducing cytotoxic T-lymphocyte (CTL) responses in both young and aged mice. Better understanding of the pathways by which antigens encoded by DNA vaccines are processed and presented to CTL may allow for improvements in CTL responses in older animals. Since CTL recognize short peptides presented by MHC class I molecules, and since ubiquitin-dependent proteolysis is widely believed to be responsible for degradation of endogenously synthesized antigens and generation of these peptide ligands, we sought to use ubiquitin (Ub) conjugation to target influenza virus nucleoprotein (NP) antigen into the Ub-proteasome degradation pathway for MHC class I-restricted antigen processing and presentation. However, the addition of the Ub moiety did not affect the half-life of Ub-NP protein in transiently transfected human rhabdomyosarcoma (RD) cells. Moreover, the modifications of NP DNA vaccine with Ub conjugation did not affect their ability to induce a CTL response specific for the H-2Kd-restricted NP147-155 epitope, as assessed by both percent cytolysis in bulk CTL culture and by CTL precursor (CTLp) frequency in limiting dilution analysis (LDA). In contrast, the anti-NP antibody (Ab) responses were dramatically reduced in mice immunized with low doses (1 microgram) of Ub-NP constructs, compared with mice immunized with wild-type NP DNA. These results demonstrate that Ub conjugation alone does not guarantee targeting of endogenously synthesized antigens for rapid degradation by proteasomes. Furthermore, the ability of ubiquintination to reduce Ab responses to NP without affecting CTL responses suggests that the Ub modifications result in a lower availability of full-length NP from transfected cells in vivo. The implications of these data on antigen presentation and cross-priming are discussed.

Animals↗
PubMed1998

Immunogenicity and efficacy of DNA vaccines encoding influenza A proteins in aged mice.

Influenza is a leading cause of morbidity and mortality in older persons. The current influenza vaccine is only modestly successful, in part because of an age-related decline in immunogenicity and also because it induces only type-specified immunity. To overcome this, we evaluated DNA vaccines encoding A/PR8/34 haemagglutinin (HA) and nucleoprotein (NP) in young and aged BALB/c mice. Control mice were given formalin-inactivated A/PR8/34, control DNA, or a non-lethal dose of PR8. Aged mice given HA DNA developed slightly lower anti-HA serum antibodies than young mice; however, both young and aged mice were protected from a homotypic PR8 challenge. Following vaccination with NP DNA, both young and aged mice developed anti-NP bulk cytotoxic T-lymphocyte (CTL) activity and pCTL frequency similar to control animals. When challenged with a low dose of A/HK/68 (H3N2) influenza virus, both young mice and aged mice showed significant protection as measured by inhibition of weight loss. When challenged with a relatively high dose of A/HR/68 (H3N2) influenza virus, however, the anti-NP vaccine only partially protected young mice and failed to protect aged mice. These data demonstrate that DNA-based vaccines are immunogenic in aged animals, but suggest that factors other than the age-related decline in CTL activity also contribute to the increased morbidity and mortality of influenza in the elderly.

Aging↗
PubMed1998

Use of free fibula flap in patients with prior failed mandibular reconstruction.

PURPOSE: The purpose of this study was to assess the efficacy of the free fibula flap in patients who had failed prior attempts at bony reconstruction. PATIENTS AND METHODS: The records of all patients who had undergone free fibula reconstruction for segmental mandibular resections between 1993 and 1995 were retrospectively reviewed. Patients were divided into group I (14 patients who had failed previous bony reconstruction attempts) and group II (50 patients who had no previous reconstruction), and the two groups were compared. RESULTS: No statistical differences were found between group I and group II for mean age, mean hospital stay, mean intensive care unit stay, mean operating room time, mean intraoperative blood loss, mean colloid usage, or mean blood units transfused. Although group I had a statistically higher proportion of both patients with osteoradionecrosis and those receiving hyperbaric oxygen therapy (HBO), the number with a history of radiation therapy was not different in the two groups. Wound complication rates were not statistically different between groups I and II for all patients, or between those group I patients who did or did not receive HBO therapy. CONCLUSION: There was no increase in wound complications in the patients who had failed prior bony reconstructive attempts who underwent free fibula flaps. The free fibula flap is suggested as the reconstructive method of choice in this patient population.

Bone Transplantation↗
PubMed1998

Structure and strength of low-mercury dental amalgams prepared with liquid Hg-47.4% In alloy.

Two low-mercury amalgams: (1) low-copper lathe-cut and (2) high-copper (Tytin) were prepared by amalgamation with liquid Hg-47.4% In alloy. The strength-structure relationship of these amalgams was investigated and compared with standard amalgams (i.e. amalgams prepared with the same powders and pure mercury). The matrix phase of the low-mercury amalgam was found to be depleted of mercury and may be thought of as In4Ag9 compound with some mercury dissolved, indicating that less mercury (compared with standard amalgam) combines with silver, thus producing a strong amalgam matrix. On the other hand, an increase was observed in the consumption of the initial gamma (Ag3Sn)-phase, leading to an increase of the tin released. As a result, the potential of [HgSn]-phase formation in low-mercury amalgams increases. The observed increase in the quantity of gamma2(Sn7-8Hg)-phase in low-copper amalgam, or its appearance in high-copper amalgam (where it is normally absent), contributes to a deterioration in the strength of the investigated amalgam. The conclusion drawn was that low-mercury amalgam may be prepared with liquid Hg-47.4%In alloy but, in order to eliminate gamma2-phase formation, novel and possibly tin-free amalgamable alloys should be developed.

Journal Article↗
PubMed1998

Gender differences in romantic jealousy.

Findings of studies of gender differences in jealousy are contradictory. In the present study, conflicting literature was addressed by distinguishing 5 dimensions of jealousy: level, trigger, experience, focus, and responses. In 4 studies, 3 in the U.S. and 1 in Israel, gender differences were explored in these 5 dimensions of romantic jealousy. Although there were no gender differences in the likelihood, frequency, duration, or intensity of jealousy, there were differences in the responses to certain jealousy-producing occasions as well as in the focus, experience, and expression of jealousy.

Adult↗
PubMed1998

De novo mutations (GAG deletion) in the DYT1 gene in two non-Jewish patients with early-onset dystonia.

The DYT1 gene recently has been cloned and shown to contain a three nucleotide (GAG) deletion responsible for most cases of autosomal dominant early-onset torsion dystonia. This deletion results in the loss of one of a pair of glutamic acids in a conserved region of a novel ATP-binding protein (torsinA). Previous haplotype analysis revealed that this same deletion had arisen at least two different times in history, suggesting independent mutational events. This deletion is the only sequence change found thus far to be associated uniquely with the disease status, regardless of ethnic origin. Here we describe two patients with typical early-onset torsion dystonia of Swiss-Mennonite and non-Jewish Russian origin, respectively, that both carry this same mutation as a de novo GAG deletion. This finding proves that this 3 bp deletion in the DYT1 gene is indeed a mutation that causes early-onset torsion dystonia. The DYT1 mutation is one of the rare examples of the same recurrent mutation causing a dominantly inherited condition. The sequence surrounding the GAG deletion contains an imperfect 24 bp tandem repeat, suggesting a possible mechanism for the high frequency of this mutation.

Adult↗
PubMed1998

Humoral immune response impairment following excess vitamin E nutrition in the chick and turkey.

The effect of high dietary intakes of vitamin E on antibody production was investigated in chicks and turkeys. Chicks were fed four diets with 0, 10, 30, and 150 mg/kg added vitamin E and turkeys were fed three diets with 0, 50, and 150 mg/kg added vitamin E. Antibodies produced in response to naturally occurring Escherichia coli and to Newcastle disease virus and turkey pox vaccines were determined. In chicks, antibody production in response to E. coli and Newcastle disease was affected by vitamin E nutrition: significantly higher responses were measured in chicks that received 0 and 10 mg/kg added vitamin E, whereas in chicks receiving 30 and 150 mg/kg, antibody production was significantly lower. In turkeys, concentrations of circulating antibodies to Newcastle disease virus and to turkey pox were also influenced by dietary vitamin E: antibody titers to Newcastle disease and turkey pox vaccines were highest in groups receiving 0 mg/kg added vitamin E, whereas titer in groups receiving 150 mg/kg were significantly lower. Responses of groups receiving 50 mg/kg added vitamin E were slightly lower than groups receiving 0 mg/kg, though not significantly so in most cases. These results indicate that humoral immune responses are directly effected by vitamin E, and that excessive vitamin E intake has a detrimental effect on antibody production in chickens and turkeys.

Animal Nutritional Physiological Phenomena↗
PubMed1998

Protective CD4+ and CD8+ T cells against influenza virus induced by vaccination with nucleoprotein DNA.

DNA vaccination is an effective means of eliciting both humoral and cellular immunity, including cytotoxic T lymphocytes (CTL). Using an influenza virus model, we previously demonstrated that injection of DNA encoding influenza virus nucleoprotein (NP) induced major histocompatibility complex class I-restricted CTL and cross-strain protection from lethal virus challenge in mice (J. B. Ulmer et al., Science 259:1745-1749, 1993). In the present study, we have characterized in more detail the cellular immune responses induced by NP DNA, which included robust lymphoproliferation and Th1-type cytokine secretion (high levels of gamma interferon and interleukin-2 [IL-2], with little IL-4 or IL-10) in response to antigen-specific restimulation of splenocytes in vitro. These responses were mediated by CD4+ T cells, as shown by in vitro depletion of T-cell subsets. Taken together, these results indicate that immunization with NP DNA primes both cytolytic CD8+ T cells and cytokine-secreting CD4+ T cells. Further, we demonstrate by adoptive transfer and in vivo depletion of T-cell subsets that both of these types of T cells act as effectors in protective immunity against influenza virus challenge conferred by NP DNA.

Animals↗
PubMed1998

Seizure onset from periventricular nodular heterotopias: depth-electrode study.

The association between gray matter heterotopias and seizures is well established; whether seizures originate from these lesions is not known. We evaluated three patients with intractable complex partial seizures and periventricular nodular heterotopias (PNHs) with video-EEG monitoring with multiple depth electrodes, including placement in the PNH, to determine whether seizures originate from the PNH. In two of the three patients, all seizures arose from the PNH as low-voltage beta activity. In the third patient, 80% arose from the hippocampi and 20% from the heterotopia. PNHs may serve as an epileptogenic focus in patients with intractable epilepsy.

Adult↗
PubMed1998

An economic evaluation of the use of rare earth screens to reduce the radiation dose from diagnostic X-ray procedures in Israel.

In Israel the diffusion of rare earth screen technology has been limited. These screens could halve the radiation dose to the patient from diagnostic X-ray radiography, with little managerial effort and without being detrimental to the quality of the diagnostic image. We estimated the total effective dose from diagnostic film radiography capable of reduction by the use of rare earth screens, based on the number of hospital and ambulatory diagnostic X-ray procedures. This number was multiplied by the computed radiation dose per body site for a series of diagnostic procedures. The annual dose was approximately 0.53 mSv per head, approximately half of which could be averted by the introduction of rare earth screen technology. Based on a fatality risk of 3% Sv-1, it is estimated that the adoption of rare earth screen technology might reduce the annual incidence of cancer by some 93 cases, half of which would be fatal after an average latency period of 18.4 years. The cost of purchasing rare earth screens on a nationwide basis is approximately $3.0 million. This cost is outweighed by a saving of $9.6 million in X-ray tube replacement costs over the period 1997-2006. Government legislation enforcing the use of rare earth screens is essential, because of the lack of prestige associated with acquiring rare earth technology, as well as institutional reluctance to accept the external benefits of reduced morbidity and mortality and/or to extend budgetary time horizons.

Cost-Benefit Analysis↗