Biomedical subjects

J D Peterson

Publications and source records attributed to J D Peterson.

At least 19 recordsLinked to original sources

PubMed2001

Complete genome sequence of a virulent isolate of Streptococcus pneumoniae.

The 2,160,837-base pair genome sequence of an isolate of Streptococcus pneumoniae, a Gram-positive pathogen that causes pneumonia, bacteremia, meningitis, and otitis media, contains 2236 predicted coding regions; of these, 1440 (64%) were assigned a biological role. Approximately 5% of the genome is composed of insertion sequences that may contribute to genome rearrangements through uptake of foreign DNA. Extracellular enzyme systems for the metabolism of polysaccharides and hexosamines provide a substantial source of carbon and nitrogen for S. pneumoniae and also damage host tissues and facilitate colonization. A motif identified within the signal peptide of proteins is potentially involved in targeting these proteins to the cell surface of low-guanine/cytosine (GC) Gram-positive species. Several surface-exposed proteins that may serve as potential vaccine candidates were identified. Comparative genome hybridization with DNA arrays revealed strain differences in S. pneumoniae that could contribute to differences in virulence and antigenicity.

Antigens, Bacterial↗

PubMed2001

The Comprehensive Microbial Resource.

One challenge presented by large-scale genome sequencing efforts is effective display of uniform information to the scientific community. The Comprehensive Microbial Resource (CMR) contains robust annotation of all complete microbial genomes and allows for a wide variety of data retrievals. The bacterial information has been placed on the Web at http://www.tigr.org/CMR for retrieval using standard web browsing technology. Retrievals can be based on protein properties such as molecular weight or hydrophobicity, GC-content, functional role assignments and taxonomy. The CMR also has special web-based tools to allow data mining using pre-run homology searches, whole genome dot-plots, batch downloading and traversal across genomes using a variety of datatypes.

Bacteria↗

PubMed2000

DNA sequence of both chromosomes of the cholera pathogen Vibrio cholerae.

Here we determine the complete genomic sequence of the gram negative, gamma-Proteobacterium Vibrio cholerae El Tor N16961 to be 4,033,460 base pairs (bp). The genome consists of two circular chromosomes of 2,961,146 bp and 1,072,314 bp that together encode 3,885 open reading frames. The vast majority of recognizable genes for essential cell functions (such as DNA replication, transcription, translation and cell-wall biosynthesis) and pathogenicity (for example, toxins, surface antigens and adhesins) are located on the large chromosome. In contrast, the small chromosome contains a larger fraction (59%) of hypothetical genes compared with the large chromosome (42%), and also contains many more genes that appear to have origins other than the gamma-Proteobacteria. The small chromosome also carries a gene capture system (the integron island) and host 'addiction' genes that are typically found on plasmids; thus, the small chromosome may have originally been a megaplasmid that was captured by an ancestral Vibrio species. The V. cholerae genomic sequence provides a starting point for understanding how a free-living, environmental organism emerged to become a significant human bacterial pathogen.

Base Sequence↗

PubMed2000

Altered responsiveness of medial prefrontal cortex neurons to glutamate and dopamine after withdrawal from repeated amphetamine treatment.

Using in vivo extracellular single-cell recording and microiontophoresis, we compared the responsiveness of medial prefrontal cortex (mPFC) neurons (layers V-VI) to dopamine and glutamate in rats that had received repeated amphetamine or saline injections. Neurons from amphetamine-pretreated rats showed increased responsiveness to glutamate and decreased responsiveness to dopamine after three days of withdrawal, suggesting that the mPFC is transiently hyperexcitable during amphetamine withdrawal. Published 2000 Wiley-Liss, Inc.

Amphetamine↗

PubMed2000

Complete genome sequence of Neisseria meningitidis serogroup B strain MC58.

The 2,272,351-base pair genome of Neisseria meningitidis strain MC58 (serogroup B), a causative agent of meningitis and septicemia, contains 2158 predicted coding regions, 1158 (53.7%) of which were assigned a biological role. Three major islands of horizontal DNA transfer were identified; two of these contain genes encoding proteins involved in pathogenicity, and the third island contains coding sequences only for hypothetical proteins. Insights into the commensal and virulence behavior of N. meningitidis can be gleaned from the genome, in which sequences for structural proteins of the pilus are clustered and several coding regions unique to serogroup B capsular polysaccharide synthesis can be identified. Finally, N. meningitidis contains more genes that undergo phase variation than any pathogen studied to date, a mechanism that controls their expression and contributes to the evasion of the host immune system.

Antigenic Variation↗

PubMed1999

Genome sequence of the radioresistant bacterium Deinococcus radiodurans R1.

The complete genome sequence of the radiation-resistant bacterium Deinococcus radiodurans R1 is composed of two chromosomes (2,648,638 and 412,348 base pairs), a megaplasmid (177,466 base pairs), and a small plasmid (45,704 base pairs), yielding a total genome of 3,284, 156 base pairs. Multiple components distributed on the chromosomes and megaplasmid that contribute to the ability of D. radiodurans to survive under conditions of starvation, oxidative stress, and high amounts of DNA damage were identified. Deinococcus radiodurans represents an organism in which all systems for DNA repair, DNA damage export, desiccation and starvation recovery, and genetic redundancy are present in one cell.

Bacterial Proteins↗

PubMed1999

Evidence for lateral gene transfer between Archaea and bacteria from genome sequence of Thermotoga maritima.

The 1,860,725-base-pair genome of Thermotoga maritima MSB8 contains 1,877 predicted coding regions, 1,014 (54%) of which have functional assignments and 863 (46%) of which are of unknown function. Genome analysis reveals numerous pathways involved in degradation of sugars and plant polysaccharides, and 108 genes that have orthologues only in the genomes of other thermophilic Eubacteria and Archaea. Of the Eubacteria sequenced to date, T. maritima has the highest percentage (24%) of genes that are most similar to archaeal genes. Eighty-one archaeal-like genes are clustered in 15 regions of the T. maritima genome that range in size from 4 to 20 kilobases. Conservation of gene order between T. maritima and Archaea in many of the clustered regions suggests that lateral gene transfer may have occurred between thermophilic Eubacteria and Archaea.

Archaea↗

PubMed1998

Analysis of leukocytes recruited to the pancreas by diabetogenic T cell clones.

To investigate host leukocytes recruited to the pancreas by diabetogenic T cells, we administered islet-specific CD4(+) T cell clones to 2-week-old nonobese diabetic (NOD) mice and examined the resulting pancreatic infiltrate by flow cytometry. Two different Vbeta4(+)CD4(+) T cell clones, BDC 2.5 and BDC 6.9, were found to recruit a heterogeneous T cell population as determined by staining with a panel of anti-TCR Vbeta monoclonal antibodies. The majority of the diabetes-initiating, Vbeta4(+) T cell clones migrated to the spleen whereas only 5-8% of the T cell population infiltrating the pancreas was Vbeta4(+). Anti-IL-2 receptor staining indicated that fewer than 10% of the total population of infiltrating lymphocytes within the pancreas were in a highly activated state. We have further found that normal splenic T cells from the NOD mouse proliferate poorly to IL-2 in vitro, yet secrete IFN-gamma in response to IL-2 stimulation. These results suggest that the recruited host T cells in our disease transfer system are not directly pathogenic but, rather, are responding to the small numbers of inflammatory T cell clones by providing cytokines that facilitate the disease process.

Animals↗

PubMed1998

Inhibition of angiogenesis by interleukin 4.

Interleukin (IL)-4, a crucial modulator of the immune system and an active antitumor agent, is also a potent inhibitor of angiogenesis. When incorporated at concentrations of 10 ng/ml or more into pellets implanted into the rat cornea or when delivered systemically to the mouse by intraperitoneal injection, IL-4 blocked the induction of corneal neovascularization by basic fibroblast growth factor. IL-4 as well as IL-13 inhibited the migration of cultured bovine or human microvascular cells, showing unusual dose-response curves that were sharply stimulatory at a concentration of 0.01 ng/ml but inhibitory over a wide range of higher concentrations. Recombinant cytokine from mouse and from human worked equally well in vitro on bovine and human endothelial cells and in vivo in the rat, showing no species specificity. IL-4 was secreted at inhibitory levels by activated murine T helper (TH0) cells and by a line of carcinoma cells whose tumorigenicity is known to be inhibited by IL-4. Its ability to cause media conditioned by these cells to be antiangiogenic suggested that the antiangiogenic activity of IL-4 may play a role in normal physiology and contribute significantly to its demonstrated antitumor activity.

Adenocarcinoma↗

PubMed1998

Glutathione levels in antigen-presenting cells modulate Th1 versus Th2 response patterns.

Current thinking attributes the balance between T helper 1 (Th1) and Th2 cytokine response patterns in immune responses to the nature of the antigen, the genetic composition of the host, and the cytokines involved in the early interaction between T cells and antigen-presenting cells. Here we introduce glutathione, a tripeptide that regulates intracellular redox and other aspects of cell physiology, as a key regulatory element in this process. By using three different methods to deplete glutathione from T cell receptor transgenic and conventional mice and studying in vivo and/or in vitro responses to three distinct antigens, we show that glutathione levels in antigen-presenting cells determine whether Th1 or Th2 response patterns predominate. These findings present new insights into immune response alterations in HIV and other diseases. Further, they potentially offer an explanation for the well known differences in immune responses in "Th1" and "Th2" mouse strains.

Animals↗

PubMed1998

Alcohol consumption alters antigen-specific Th1 responses: mechanisms of deficit and repair.

Among the physiological effects associated with excessive alcohol consumption are alterations in immune function. Alcohol impairs T-helper 1 lymphocyte (Th1) regulated, cell-mediated immune responses. Antibody responses, regulated by T-helper 2 lymphocyte (Th2), are either unimpaired or enhanced. Antigen presenting cells are central to the development of both Th1 and Th2 regulated immune responses. We used both T-cell receptor transgenic and conventionally immunized mice to demonstrate that ethanol consumption directly affects antigen presenting cells that, in turn, determines whether Th1 or Th2 response patterns predominate. Ethanol consumption inhibits Th1-associated interleukin-12 and interferon-gamma cytokine production and delayed-type hypersensitivity. Administration of exogenous recombinant interleukin-12 both restores interferon-gamma levels and delayed-type hypersensitivity responses in ethanol-consuming mice.

Alcoholism↗

PubMed1998

Human antibody responses to Trypanosoma cruzi 70-kD heat-shock proteins.

Heat-shock proteins of the 70-kD (hsp70) family are targets of humoral and cellular immune responses following bacterial or parasitic infections, including Chagas' disease. In the present study, we measured antibodies in human sera reactive with hsp70s from the cytoplasm (cy-hsp70), mitochondrion (mt-hsp70), and endoplasmic reticulum (grp78) of Trypanosoma cruzi. Of the three hsp70s tested, only grp78 detected T. cruzi infection in more than 90% of nontreated (NT) patients, with cy-hsp70 and mt-hsp70 detecting only 78% and 25% of NT patients, respectively. Reactivity of leishmanial sera was 77% with cy-hsp70, 13% with grp78, and 5% with mt-hsp70. Therefore, considering sensitivity and specificity, the best candidate for T. cruzi serodiagnosis is grp78. Combination of grp78 with a T. cruzi 24-kD flagellar calcium binding protein (FCaBP) increased the diagnostic sensitivity from 90% to 97% but increased leishmanial reactivity from 3% to 8%. To determine whether hsp70s are useful for discriminating between cured and noncured patients treated with trypanocidal drugs, we tested sera from treated noncured (TNC) patients and cured patients who have positive conventional serology, termed treated dissociated (TD). The cy-hsp70 and grp78 reacted with 74% and 68% of TNC patient sera, respectively, but these antigens did not discriminate TNC from TD patients (52% and 45% positive, respectively). The mt-hsp70 was detected by sera from few TNC patients (18%) and no TD patients. Although individual hsp70s were not useful for determining the effect of trypanocidal drugs on T. cruzi infection in individual patients, the majority of TNC patient sera (70-80%) reacted with two or three of the hsp70s. In contrast, no TD sera reacted with all three hsp70s, and 40% did not react with any of the hsp70s, indicating that the number of hsp70s detected decreases following successful treatment. Considered together, these results show that grp78 has potential as a diagnostic antigen and that absence of reactivity to all three hsp70s may be indicative of effective treatment.

Animals↗

PubMed1998

Interleukin-12 therapy restores cell-mediated immunity in ethanol-consuming mice.

Previous studies from our laboratory show that ethanol consumption impairs antigen-specific, cell-mediated, but not, humoral immune responses of C57BL/6, BALB/c, and DO11.10 T-cell receptor transgenic mice. This ethanol-associated deficit is associated with decreased interleukin (IL)-12 and interferon-gamma (IFN-gamma) production, but not IL-2 or antigen-specific T-cell proliferation by explanted leukocytes from ethanol-consuming mice. IL-12 expression by macrophage/monocytes is viewed as a requirement for the production of IFN-gamma by Th1 lymphocytes that mediate cellular immunity. In this study, we restored antigen-specific, cell-mediated immunity, delayed hypersensitivity, to ethanol-consuming C57BL/6 or BALB/c mice with a single 100 ng of intravenous injection of recombinant IL-12 at the time of immunization. The addition of exogenous recombinant IL-12 to co-cultures of antigen-presenting cells derived from ethanol-consuming mice and purified T cells derived from ethanol-nonconsuming DO11.10 repairs the ability of Th1 cells to make IFN-gamma in response to antigen. Administration of recombinant IL-12 opens a potential for restoring cell-mediated immune function to ethanol-consuming individuals.

Alcoholism↗

PubMed1997

The complete genome sequence of the hyperthermophilic, sulphate-reducing archaeon Archaeoglobus fulgidus.

Archaeoglobus fulgidus is the first sulphur-metabolizing organism to have its genome sequence determined. Its genome of 2,178,400 base pairs contains 2,436 open reading frames (ORFs). The information processing systems and the biosynthetic pathways for essential components (nucleotides, amino acids and cofactors) have extensive correlation with their counterparts in the archaeon Methanococcus jannaschii. The genomes of these two Archaea indicate dramatic differences in the way these organisms sense their environment, perform regulatory and transport functions, and gain energy. In contrast to M. jannaschii, A. fulgidus has fewer restriction-modification systems, and none of its genes appears to contain inteins. A quarter (651 ORFs) of the A. fulgidus genome encodes functionally uncharacterized yet conserved proteins, two-thirds of which are shared with M. jannaschii (428 ORFs). Another quarter of the genome encodes new proteins indicating substantial archaeal gene diversity.

Archaeoglobus fulgidus↗

PubMed1997

The complete genome sequence of the gastric pathogen Helicobacter pylori.

Helicobacter pylori, strain 26695, has a circular genome of 1,667,867 base pairs and 1,590 predicted coding sequences. Sequence analysis indicates that H. pylori has well-developed systems for motility, for scavenging iron, and for DNA restriction and modification. Many putative adhesins, lipoproteins and other outer membrane proteins were identified, underscoring the potential complexity of host-pathogen interaction. Based on the large number of sequence-related genes encoding outer membrane proteins and the presence of homopolymeric tracts and dinucleotide repeats in coding sequences, H. pylori, like several other mucosal pathogens, probably uses recombination and slipped-strand mispairing within repeats as mechanisms for antigenic variation and adaptive evolution. Consistent with its restricted niche, H. pylori has a few regulatory networks, and a limited metabolic repertoire and biosynthetic capacity. Its survival in acid conditions depends, in part, on its ability to establish a positive inside-membrane potential in low pH.

Antigenic Variation↗

PubMed1996

Transfer of diabetes in the NOD-scid mouse by CD4 T-cell clones. Differential requirement for CD8 T-cells.

Transfer of an interleukin 2/interferon-gamma-secreting islet-specific CD4+ T-cell clone, BDC-6.9, in the immunodeficient NOD-scid mouse induces destruction of pancreatic beta-cells without help from host B-cells, CD4+ T-cells, or CD8+ T-cells. However, a second islet-specific T-cell clone, BDC-2.5, showing the same cytokine profile and T-cell receptor Vbeta expression as BDC-6.9 was not capable of inducing diabetes or insulitis in NOD-scid mice. Even though BDC-2.5 by itself readily induces diabetes in young unmanipulated NOD mice, cotransfer of CD8-enriched T-cells was required to induce disease in NOD-scid mice. Immunohistochemical staining of pancreatic lesions in young NOD mice receiving either BDC-2.5 or BDC-6.9 showed the presence of CD4+, CD8+, Vbeta4+, and MAC-1+ cells within the infiltrate, similar to infiltrates in lesions of spontaneously diabetic female NOD mice. In contrast, NOD- scid mice that received BDC-6.9 showed only the presence of CD4+Vb4+ T-cells and a large population of MAC-1+ cells in islet lesions. NOD-scid recipients of cotransferred BDC- 2.5/CD8+ splenic T-cells showed a small population of CD4+ T-cells and a larger population of CD8+ T-cells within the infiltrated islets, whereas no infiltrate was detectable in recipients of CD8+ splenocytes or BDC-2.5 alone. Our results suggest that at least two types of islet-specific CD4+ T-cell clones play a role in diabetes pathogenesis.

Animals↗

PubMed1995

Inhibition of Theiler's virus-mediated demyelination by peripheral immune tolerance induction.

Theiler's murine encephalomyelitis virus (TMEV), a member of the cardiovirus subfamily of the Picornaviridae, is a natural pathogen of mice. Thirty to 60 days following intracerebral infection with TMEV, susceptible inbred mouse strains develop a chronic, progressive, T cell-mediated inflammatory demyelinating disease of the central nervous system (CNS) characterized by spastic hind limb paralysis and a lifelong persistent CNS virus infection. We have examined the effect of peripheral virus-specific tolerance on the development of demyelinating disease. Treatment of SJL/J mice with TMEV-coupled, ethyl carbodiimide-treated splenocytes either before or after infection with live TMEV prevented the development of clinical disease, including inflammation and demyelination in the CNS. Prevention of clinical disease was paralleled by significant reductions in virus-specific immune responses, including delayed type hypersensitivity and T cell proliferative responses. Tolerance induction resulted in a significant reduction in the absolute numbers of mononuclear cells infiltrating the CNS, particularly the CD4+IL-2R+ T cell subset, 3, 5, and 8 wk postinfection. In contrast, tolerance induction had no effect on the numbers of CD8+IL-2R+ T cells infiltrating the CNS. Treatment with TMEV-coupled splenocytes failed to prevent the development of relapsing experimental autoimmune encephalomyelitis, demonstrating the specificity of in vivo tolerance induction. Prevention of demyelinating disease did not correlate with the increased TMEV-specific Ab responses observed in tolerized mice. These results indicate that induction of immune tolerance to TMEV can down-regulate a chronic immunopathogenic disease directed against virus Ag persisting in the CNS that normally results in a progressive demyelinating disease similar to multiple sclerosis.

Animals↗

PubMed1995

Induction of diabetes with islet-specific T-cell clones is age dependent.

To investigate the effects of recipient age on the induction of diabetes by CD4+ islet-specific T-cell clones, we tested four different clones in non-obese diabetic (NOD) mice of different ages. Transfer of each of the T-cell clones resulted in insulitis and full development of diabetes in unirradiated 8-18-day-old NOD mice within 2-3 weeks. A small gender bias in disease susceptibility was seen in 8-14-day-old female NOD mice, which showed a twofold increase in disease incidence over both age-matched males and slightly older (15-18-day-old) females. In contrast, both male and female NOD mice, 19 days or older, were highly resistant to T-cell clone-induced insulitis and completely resistant to the development of diabetes. In mice of an intermediate age range (15-18 days old), two of the clones showed a three- to fourfold reduction in transfer of overt diabetes regardless of gender. These results suggest that an important developmental event occurs in both male and female NOD mice between the age of 15 and 19 days, leading to the inhibition of disease induced by T-cell clones.

Age Factors↗