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Biomedical subjects

J Sternberg

Publications and source records attributed to J Sternberg.

At least 19 recordsLinked to original sources
PubMed2006

Properties of pseudopotentials for higher partial waves.

Contact psuedopotentials for relative angular momentum greater than zero are of interest for the study of cold atomic gases. For bosons, it is known that when the s-wave scattering length becomes infinite, an infinite number of three-body bound states, called Efimov states, are predicted by such potentials. Realistic potentials also exhibit the such states, thus a study of the Efimov effect for contact psuedopotentials for higher partial waves and fermions is important for the study of cold atoms. In this Letter we analyze three-body states of three particles interacting via psuedopotentials for higher partial waves and show that there is an Efimov effect for three fermions interacting via p-wave psuedopotentials.

Journal Article↗
PubMed2006

Regulation of vesicular monoamine and glutamate transporters by vesicle-associated trimeric G proteins: new jobs for long-known signal transduction molecules.

Neurotransmitters of neurons and neuroendocrine cells are concentrated first in the cytosol and then in either small synaptic vesicles ofpresynaptic terminals or in secretory vesicles by the activity of specific transporters of the plasma and the vesicular membrane, respectively. In the central nervous system the postsynaptic response depends--amongst other parameters-on the amount of neurotransmitter stored in a given vesicle. Neurotransmitter packets (quanta) vary over a wide range which may be also due to a regulation of vesicular neurotransmitter filling. Vesicular filling is regulated by the availability of transmitter molecules in the cytoplasm, the amount of transporter molecules and an electrochemical proton-mediated gradient over the vesicular membrane. In addition, it is modulated by vesicle-associated heterotrimeric G proteins, Galphao2 and Galphaq. Galphao2 and Galphaq regulate vesicular monoamine transporter (VMAT) activities in brain and platelets, respectively. Galphao2 also regulates vesicular glutamate transporter (VGLUT) activity by changing its chloride dependence. It appears that the vesicular content activates the G protein, suggesting a signal transduction from the luminal site which might be mediated by a vesicular G protein-coupled receptor or as an alternative possibility by the transporter itself. Thus, G proteins control transmitter storage and thereby probablylink the regulation of the vesicular content to intracellular signal cascades.

Animals↗
PubMed2000

Hypocaloric total parenteral nutrition: effectiveness in prevention of hyperglycemia and infectious complications--a randomized clinical trial.

OBJECTIVE: To determine whether the frequency rate of hyperglycemia and infectious complications can be reduced by an underfeeding strategy in patients requiring total parenteral nutrition (TPN), without deleterious effects on nitrogen balance. DESIGN: Prospective, randomized, controlled nonblinded trial. SETTING: A university-affiliated teaching hospital with a dedicated TPN service. PATIENTS: TPN was initiated in 40 adult patients and continued for > or =5 days. INTERVENTION: Two different TPN feeding strategies were compared: hypocaloric feeding (1 L containing 70 g protein and 1000 kcal) and standard weight-based regimen, begun in similar amounts initially, but advanced in increments toward 25 kcal and 1.5 g protein/kg dry (or adjusted ideal) weight. MEASUREMENTS AND MAIN RESULTS: We evaluated the frequency rate of hyperglycemia, average blood glucose, numbers and types of infections while receiving nutritional support and nitrogen balance after 5 days of TPN. There were significant differences between the quantities of calories, dextrose, fat, and protein provided to the two groups. However, average blood glucose, frequency rate of hyperglycemia, and infection rates (from intravenous catheter, pneumonia, and wound/abdominal collection) were similar in each group. The control group showed a trend toward a higher insulin requirement. Nitrogen balance, only available as a subset, was significantly more negative in the hypocaloric group. CONCLUSIONS: Provision of TPN to a goal of 25 kcal/kg was not associated with more hyperglycemia or infections than a deliberate underfeeding strategy. A regimen of 1.5 g/kg protein in conjunction with 25 kcal/kg did, however, provide significant nutritional benefit in terms of nitrogen balance in comparison with hypocaloric TPN.

Adult↗
PubMed1999

T-Cell responses during Trypanosoma brucei infections in mice deficient in inducible nitric oxide synthase.

We have investigated the possibility that nitric oxide (NO) synthesis may affect the course of a trypanosome infection via T-cell responses using mice deficient in inducible NO synthase (iNOS). Parasitemia levels increased at the same rate in both iNOS-deficient homozygous and control heterozygous mice, and peak parasitemia values were the same in both groups. However, the heterozygous mice maintained higher parasitemia levels after the peak of an infection than the homozygous mice due to a decrease in the rate of clearance of parasites. In iNOS-deficient mice there was an increase in the numbers of total CD4(+) cells and activated (interleukin-2 receptor-expressing) CD4(+) cells in infected mice compared with the numbers in uninfected mice. Spleen cells from infected iNOS-deficient mice displayed increased proliferative responses and gamma interferon secretion when stimulated in vitro than those of control mice. These data suggest that NO production depresses T-helper 1-like responses generated during Trypanosoma brucei infections, thus promoting the survival of the parasite.

Animals↗
PubMed1995

Bone marrow nitric oxide production and development of anemia in Trypanosoma brucei-infected mice.

Mice infected with Trypanosoma brucei rapidly develop anemia, with the number of circulating erythrocytes reduced by 50% within a week after infection. The present study investigated the relationship between anemia and bone marrow nitric oxide (NO) production. Bone marrow cell populations from T. brucei-infected mice exhibited elevated levels of NO synthase activity which was inhibitable by NG-nitro-L-arginine methyl ester. NO production was found to coincide with suppressed bone marrow T-cell proliferation in response to stimulation with the mitogen concanavalin A both in vitro and in vivo. As this indicated that NO may inhibit proliferation in other cell types, particularly hemopoietic precursors, we examined the role of NO in anemia during trypanosome infection. NO production correlated directly with the development of anemia, and treatment of infected mice with NG-nitro-L-arginine methyl ester in vivo to systemically inhibit NO synthesis led to a significant reduction in the anemia. Thus, elevated NO production in the bone marrow of T. brucei-infected mice is likely to play a significant role in the anemia resulting from T. brucei infection.

Anemia↗
PubMed1994

Inhibition of nitric oxide synthesis leads to reduced parasitemia in murine Trypanosoma brucei infection.

In murine Trypanosoma brucei infection, macrophage activation and nitric oxide (NO) production lead to suppressed splenic T-cell responses (J. Sternberg and F. McGuigan, Eur. J. Immunol. 22:2741-2744, 1992). In this study, evidence is presented that NO has no detectable trypanocidal activity under simulated in vivo conditions and that inhibition of NO production in vivo results in reduced parasitemia.

Animals↗
PubMed1993

Semiconductor laser-induced fluorescence detection in capillary electrophoresis using a cyanine dye.

Cy5, an activated carboxyl cyanine fluorophore, was characterized by capillary electrophoresis (CE) using a semiconductor laser at 652 nm to induce fluorescence. Hydrolysis of the activated Cy5 in the presence of ammonia results in the formation of a mono- and diamide and a dicarboxylic acid. A Cy5-labeled oligonucleotide M13 primer for DNA sequencing (M13mp18 template) was synthesized with a purity of better than 95%. The labeled primer was analyzed by liquid chromatography, using UV-visible detection, and by CE, monitored by laser-induced fluorescence (LIF) detection. Analysis of the Cy5-labeled oligonucleotide primer by CE-LIF in a 9% polyacrylamide gel-filled capillary indicated the purity of the major Cy5-oligonucleotide primer was greater than 90%. The detection sensitivity for Cy5-based CE-LIF detection system with a 2.5-mW red semiconductor laser is about 10(-10) M.

Base Sequence↗
PubMed1992

Nitric oxide mediates suppression of T cell responses in murine Trypanosoma brucei infection.

African trypanosomes induce a generalized state of immunosuppression in their mammalian hosts. One characteristic of this is a suppression of lymphocyte responses to mitogen, which is mediated by suppressor macrophages. We investigated the involvement of nitric oxide in this phenomenon. Both peritoneal and splenic cell cultures from infected mice released nitrite and this was inhibitable by NG-monomethyl L-arginine (L-NMMA). The release of nitrite correlated with suppressed splenic T cell proliferative responses to concanavalin A. It was shown that adherent spleen cells from infected mice mediate suppression, which could be abrogated by L-NMMA. These results suggest that in T. brucei infection, the activation of macrophages to produce nitric oxide leads to impaired lymphocyte responses and immunosuppression.

Animals↗
PubMed1990

Genetic exchange in African trypanosomes.

African trypanosomes are important pathogens of humans and domestic animals, but little was known, until recently, of the genetic system of these parasites. Recent results demonstrate the existence of nonobligatory genetic exchange between different stocks of T. brucei. A number of models have been put forward for the mechanism of genetic exchange, including a fusion model with subsequent random loss of chromosomes and a more conventional mendelian system.

Animals↗
PubMed1990

Evidence that the mechanism of gene exchange in Trypanosoma brucei involves meiosis and syngamy.

All pairwise combinations of three cloned stocks of Trypanosoma brucei (STIB 247L, STIB 386AA and TREU 927/4) were co-transmitted through tsetse flies (Glossina morsitans) and screened for the production of hybrid trypanosomes. Clones of metacyclic and bloodstream trypanosomes from flies harbouring mature infections containing hybrid trypanosomes were established and screened for several isoenzyme and restriction fragment length polymorphisms. For each of the three combinations of parents, some progeny clones were observed to be of a phenotype and genotype indicating that genetic exchange had occurred during development of the trypanosomes in flies. These hybrid clones shared three salient features: (1) where the parents were homozygous variants the progeny were heterozygous, (2) where one of the parents was heterozygous, allelic segregation was observed and (3) the progeny clones were shown to be recombinant when two or more markers for which one of the parents was heterozygous were examined. These results are consistent with the progeny being an F1 in a diploid mendelian genetic system involving meiosis and syngamy. Our observations show that all possible combinations of the three stocks may undergo genetic exchange. A marker analysis of a series of clones each derived from single metacyclic trypanosomes showed that individual flies transmit a mixture of trypanosome genotypes corresponding to F1 progeny and to parental types, indicating that genetic exchange was a non-obligatory event in the life-cycle of the trypanosome. In addition, a preliminary analysis of the phenotype of procyclic stage trypanosomes derived from flies infected with two stocks, indicates that genetic exchange is unlikely to occur at this stage.

Alleles↗
PubMed1989

Gene exchange in African trypanosomes: frequency and allelic segregation.

The existence of a system of genetic exchange in Trypanosoma brucei is now established, but the frequency with which mating occurs and the mechanisms by which genes are exchanged are still unknown. This paper presents the results of a study of one pair of trypanosome stocks, which show that mating is a non-obligatory but frequent event in a life-cycle stage within the insect vector. Analysis of ten progeny clones using a total of eleven markers (iso-enzymes and DNA probes detecting restriction fragment length polymorphisms) has indicated that segregation of alleles occurs at five of these loci. The segregation patterns of a polymorphic EcoRI site in the maxi-circle of the kinetoplast DNA (kDNA) show that the progeny inherit one or other of the parental kDNA types. These results demonstrate that segregation of alleles occurs and that new combinations of alleles at different loci are generated in the progeny clones. The implications of these findings for defining the mechanism of gene exchange are discussed in relation to a simple mendelian genetic system involving meiosis and syngamy.

Alleles↗
PubMed1989

Neuropeptide expression in cultures of adult sensory neurons: modulation of substance P and calcitonin gene-related peptide levels by nerve growth factor.

In contrast to developing sensory neurons, the survival of adult rat dorsal root ganglion neurons in pure neuronal culture is not dependent on specific neurotrophic factors such as nerve growth factor or brain-derived neurotrophic factor [Lindsay R. M. (1988) J. Neurosci. 8, 2394-2405]. In the present study we have examined possible modulatory effects of nerve growth factor on the neuropeptide content of sub-populations of adult rat dorsal root ganglion neurons in vitro. During the first 1-2 days in culture the neuropeptides substance P and calcitonin gene-related peptide could be detected by immunofluorescence staining in cultures grown in the presence or absence of nerve growth factor, but at longer times in nerve growth factor-deprived cultures there was loss of immunoreactive staining for both peptides. In the presence of nerve growth factor, however, the percentage of substance P- and calcitonin gene-related peptide-immunoreactive neurons remained relatively constant, for at least 14 days, at levels that were similar to the percentage of such peptide-containing neurons found in sections of adult rat dorsal root ganglia. Quantitation by radioimmunoassay of the levels of substance P and calcitonin gene-related peptide in cultures grown in the presence or absence of nerve growth factor agreed with the qualitative observations obtained by immunofluorescence: 10-15-fold higher levels of substance P and calcitonin gene-related peptide were found in cultures grown with nerve growth factor for 18 days, as compared to nerve growth factor-deprived cultures. In nerve growth factor-treated cultures increased levels of substance P and calcitonin gene-related peptide were observed within 3-6 days in vitro, and further steady increases in the levels of both peptides were found up to 18 days. A low basal level of both peptides could always be detected, even in the presence of an excess of antibodies to nerve growth factor. Up-regulation of the synthesis of substance P and calcitonin gene-related peptide did not depend on nerve growth factor being present at the initiation of the cultures, as elevated levels of both peptides could be induced in cultures even after up to 10 days' prior deprivation of nerve growth factor. Removal of nerve growth factor from the cultures resulted in reduced levels of peptide within 3 days.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

Gene exchange in African trypanosomes: characterisation of a new hybrid genotype.

We describe the isolation of a hybrid Trypanosoma brucei clone following the mixed cyclical transmission of two parental clones through tsetse flies. The characterisation of this clone reveals some new facets of the process of genetic exchange in T. brucei. The inheritance of four isoenzyme loci and restriction fragment polymorphisms at two loci was interpretable in 'mendelian' genetic terms, involving meiosis either before or after the genetic exchange event. However, at a further two isoenzyme loci a deviation from mendelian behaviour was observed. Pulse field gel analysis showed that the hybrid clone possessed a new combination of intermediate size chromosomes. Examination of kinetoplast DNA variants showed uniparental kinetoplast inheritance, and with reference to previous work we conclude that the kinetoplast can be inherited from either parent. The nuclear DNA content of the hybrid clone was measured and found to be identical to the parental nuclear DNA contents. This finding, together with the inheritance of isoenzyme and RFLP markers, is discussed with respect to possible models for genetic exchange.

Animals↗
PubMed1988

Nerve growth factor (NGF) regulates adult rat cultured dorsal root ganglion neuron responses to the excitotoxin capsaicin.

An overlap between subpopulations of nerve growth factor (NGF)-responsive and capsaicin-sensitive dorsal root ganglion (DRG) sensory neurons has been suggested from a number of in vivo studies. To examine this apparent link in more detail, we compared the effects of capsaicin on adult rat DRG neurons cultured in the presence or absence of NGF. Capsaicin sensitivity was assessed histochemically by a cobalt staining method, by measuring capsaicin-induced 45Ca2+ uptake, and by electrophysiological recording of capsaicin-evoked membrane currents. When cultured with NGF, approximately 50% of these adult DRG neurons were capsaicin-sensitive, whereas adult sympathetic neurons or ganglionic nonneuronal cells were insensitive. DRG cultures grown in the absence of NGF, however, were essentially unresponsive to capsaicin. Capsaicin sensitivity could be regained fully within 4-6 days of replacement of NGF. These results indicate that, at least in vitro, NGF can modify the capsaicin sensitivity of adult DRG neurons.

Animals↗