The effects of interleukin-10 depletion in vivo on the immune response to Porphyromonas gingivalis in a murine model

Background: The immune response to Porphyromonas gingivalis in the mouse abscess model is known to be dependent upon CD4 T-cell activation and the regulatory role of cytokines. The role of interleukin-10 (IL-10) in this mouse model was examined in vivo. Methods: One-week-old, female BALB/c mice were divided into 4 groups. Groups 1 and 2 were given intraperitoneal (ip) injections of phosphate buffered saline (PBS) weekly for 5 weeks. Group 3 was given an ip injection of rat immunoglobulin. Group 4 was injected with rat anti-IL-10 antibodies. At week 6, group 1 was sham-immunized with PBS, and groups 2, 3, and 4 were injected with P gingivalis lipopolysaccharide (Pg-LPS) weekly for 2 weeks. One week after the final immunization, delayed-type hypersensitivity (DTH) was assessed by footpad swelling to Pg-LPS. The level of serum antibodies to Pg-LPS and IFN-gamma (IFN-gamma) was determined by enzyme-linked immunosorbent assay. Dorsal abscess formation induced by the injection of viable P gingivalis was examined daily for 30 days. Results: The footpad swelling of the anti-IL-10-treated group (group 4) was significantly higher than that of groups 1 to 3. Similarly, the serum IFN-gamma level in group 4 was much higher than that of the other experimental groups. There was no significant difference in serum IgG antibodies to Pg-LPS in any of the experimental groups. However, the level of IgM antibodies in group 4 mice was significantly lower than that in groups 2 and 3. In addition, serum IgG1 was suppressed in group 4 mice, while IgG2a antibodies were raised. However, there was no difference observed between the levels of IgG2b and IgG3 antibodies in any group of mice. The lesions in sham-immunized mice (group 1) persisted for 30 days, and those in group 2 and 3 were undetected by day 18 and 20, respectively. In sharp contrast, lesions in group 4 had healed completely by day 13. Conclusions: This study has shown that IL-10 depletion in vivo in P gingivalis LPS-induced immune response in mice led to an elevated DTH response, an increase in serum IFN-gamma levels, and raised levels of IgG and IgG2a antibodies. Treatment with anti-IL-10 antibodies resulted in suppressed IgG I and IgM responses and a more rapid healing of abscesses than in non-IL-10-depleted mice. These results suggest that IL-10 depletion in Pg-LPS-induced immune response in mice may lead to a Th1-like immune response and provide strong protection against a subsequent challenge with live P gingivalis in an abscess model.

Olfaction in the Queensland fruit fly, Bactrocera tryoni. I: Identification of olfactory receptor neuron types responding to environmental odors

The electroantennogram method was used to investigate the number of distinct olfactory receptor neuron types responding to a range of behaviorally active volatile chemicals in gravid Queensland fruit flies, Bactrocera tryoni. Three receptor neuron types were identified. One type responds to methyl butyrate, 2-butanone, farnesene, and carbon dioxide; a second to ethanol; and a third to n-butyric acid and ammonia. The receptor neuron type responding to methyl butyrate, 2-butanone, farnesene, and carbon dioxide consists of three subtypes. The presence of a limited number of receptor neuron types responding to a diverse set of chemicals and the reception of carbon dioxide by a receptor neuron type that responds to other odorants are novel aspects of the peripheral olfactory discrimination process.

Precipitation hardening of Cu-Fe-Cr alloys - Part I - Mechanical and electrical properties

This research is part of a project whose scope was to investigate the engineering properties of new non-commercial alloy formulations based on the Cu rich corner of the Cu-Fe-Cr ternary system with the primary aim of exploring the development of a new cost-effective high-strength, high-conductivity copper alloy. The literature indicated that Cu rich Cu-Cr and Cu-Fe alloys have been thoroughly investigated. A number of commercial alloys have been developed and these are used for a variety of applications requiring combinations of high-strength, high-conductivity and resistance to softening. Little evidence was found in the literature that the Cu rich corner of the Cu-Fe-Cr system had previously been investigated for the purpose of developing high-strength, high-conductivity copper alloys resistant to softening. The aim of these present investigations was to explore the possibility that new alloys could be developed that combined the properties of both sets of alloys, ie large precipitation hardening response combined with the ability to stabilise cold worked microstructures to high temperatures while at the same maintain high electrical conductivity. To assess the feasibility of this goal the following alloys were chosen for investigation: Cu-0.7wt%Cr-0.3wt%Fe, Cu-0.7wt%Cr-0.8wt%Fe, Cu-0.7wt%Cr-2.0wt%Fe. This paper reports on the mechanical property investigation which indicated that the Cu-0.7wt%Cr-0.3wt%Fe, and Cu-0.7wt%Cr-2.0wt%Fe alloys were worthy of further investigation. (C) 2001 Kluwer Academic Publishers.

Brain activity during the encoding, retention, and retrieval of stimulus representations

Studies of delayed nonmatching-to-sample (DNMS) performance following lesions of the monkey cortex have revealed a critical circuit of brain regions involved in forming memories and retaining and retrieving stimulus representations. Using event-related functional magnetic resonance imaging (fMRI), we measured brain activity in 10 healthy human participants during performance of a trial-unique visual DNMS task using novel barcode stimuli. The event-related design enabled the identification of activity during the different phases of the task (encoding, retention, and retrieval). Several brain regions identified by monkey studies as being important for successful DNMS performance showed selective activity during the different phases, including the mediodorsal thalamic nucleus (encoding), ventrolateral prefrontal cortex (retention), and perirhinal cortex (retrieval). Regions showing sustained activity within trials included the ventromedial and dorsal prefrontal cortices and occipital cortex. The present study shows the utility of investigating performance on tasks derived from animal models to assist in the identification of brain regions involved in human recognition memory.

A phylogeny for the genus Isoodon and a range extension for I-obesulus peninsulae based on mtDNA control region and morphology

Short-nosed bandicoots, Isoodon, have undergone marked range contractions since European colonisation of Australia and are currently divided into many subspecies, the validity of which is debated. Discriminant function analysis of morphology and a phylogeny of Isoodon based on mtDNA control region sequences indicate a clear split between two of the three recognised species, I. macrourus and I. obesulus/auratus. However, while all previously recognised taxa within the I. obesulus/auratus group are morphologically distinct, I. auratus and I. obesulus are not phylogenetically distinct for mtDNA. The genetic divergence between I. obesulus and I. auratus (2.6%) is similar to that found among geographic isolates of the former (I. o. obesulus and I. o. peninsulae: 2.7%). Further, the divergence between geographically close populations of two different species (I. o. obesulus from Western Australia and I. a. barrowensis: 1.2%) is smaller than that among subspecies within I. auratus (I. a. barrowensis and I. auratus from northern Western Australia: 1.7%). A newly discovered population of Isoodon in the Lamb Range, far north Queensland, sympatric with a population of I. m. torosus, is shown to represent a range extension of I. o. peninsulae (350 km). It seems plausible that what is currently considered as two species, I. obesulus and I. auratus, was once one continuous species now represented by isolated populations that have diverged morphologically as a consequence of adaptation to the diverse environments that occur throughout their range. The taxonomy of these populations is discussed in relation to their morphological distinctiveness and genetic similarity.

Antibody levels to the class I and II epitopes of the M protein and myosin are related to group A streptococcal exposure in endemic populations

Rheumatic fever (RF)/rheumatic heart disease (RHD) and post-streptococcal glomerulonephritis are thought to be autoimmune diseases, and follow group A streptococcal (GAS) infection. Different GAS M types have been associated with rheumatogenicity or nephritogenicity and categorized into either of two distinct classes (I or II) based on amino acid sequences present within the repeat region ('C' repeats) of the M protein. Sera from ARF patients have previously been shown to contain elevated levels of antibodies to the class I-specific epitope and myosin with the class I-specific antibodies also being cross-reactive to myosin, suggesting a disease association. This study shows that immunoreactivity of the class I-specific peptide and myosin does not differ between controls and acute RF (ARF)/RHD in populations that are highly endemic for GAS, raising the possibility that the association is related to GAS exposure, not the presence of ARF/RHD. Peptide inhibition studies suggest that the class I epitope may be conformational and residue 10 of the peptide is critical for antibody binding. We demonstrate that correlation of antibody levels between the class I and II epitope is due to class II-specific antibodies recognizing a common epitope with class I which is contained within the sequence RDL-ASRE. Our results suggest that antibody prevalence to class I and II epitopes and myosin is associated with GAS exposure, and that antibodies to these epitopes are not an indicator of disease nor a pathogenic factor in endemic populations.

Transport of endosomal early antigen I in the rat sciatic nerve and location in cultured neurons

Early endosomal antigen I (EEAI) is known to be a marker of early endosomes and in cultured hippocampal neurons it preferentially localizes to the dendritic but not the axonal compartment. We show in cultured dorsal root ganglia and superior cervical ganglia neurons that EEAI localizes to the cell bodies and the neurites of both sensory and sympathetic neurons. We then show in vivo using a ligated rat sciatic nerve that EEAI significantly accumulates on the proximal side and not on the distal side of the ligation. This suggests that EEAI is transported in the anterograde direction in axons either as part of the homeostatic process or to the nerve ligation site in response to nerve injury. NeuroReport 12:281-284 (C) 2001 Lippincott Williams & Wilkins.

Developmental changes in hyperpolarization-activated currents I-h and I-K(IR) in isolated rat intracardiac neurons

The hyperpolarization-activated nonselective cation current, I-h, was investigated in neonatal and adult rat intracardiac neurons. I-h was observed in all neurons studied and displayed slow time-dependent rectification. I-h was isolated by blockade with external Cs+ (2 mM) and was inhibited irreversibly by the bradycardic agent, ZD 7288. Current density of I-h was approximately twofold greater in neurons from neonatal (-4.1 pA/pF at -130 mV) as compared with adult (-2.3 pA/pF) rats; however, the reversal potential and activation parameters were unchanged. The reversal potential and amplitude of I-h was sensitive to changes in external Na+ and K+ concentrations. An inwardly rectifying K+ current, I-K(IR), was also present in intracardiac neurons from adult but not neonatal rats and was blocked by extracellular Ba2+. I-K(IR) was present in approximately one-third of the adult intracardiac neurons studied, with a current density of -0.6 pA/pF at -130 mV. I-K(IR) displayed rapid activation kinetics and no time-dependent rectification consistent with the rapidly activating, inward K+ rectifier described in other mammalian autonomic neurons. I-K(IR) was sensitive to changes in external K+, whereby raising the external K+ concentration from 3 to 15 mM shifted the reversal potential by approximately +36 mV. Substitution of external Na+ had no effect on the reversal potential or amplitude of I-K(IR). I-K(IR) density increases as a function of postnatal development in a population of rat intracardiac neurons, which together with a concomitant decrease in I-h may contribute to changes in the modulation of neuronal excitability in adult versus neonatal rat intracardiac ganglia.

Peritoneal cytology: impact on disease-free survival in clinical stage I endometrioid adenocarcinoma of the uterus

The prognostic significance of positive peritoneal cytology in endometrial carcinoma has led to the incorporation of peritoneal cytology into the current FIGO staging system, While cytology was shown to be prognostically relevant in patients with stage II and III disease, conflicting data exists about its significance in patients who would have been stage I but were classified as stage III solely and exclusively on the basis of positive peritoneal cytology (clinical stage I). Analysis was based on the data of 369 consecutive patients with clinical stage I endometrioid adenocarcinoma of the endometrium. Standard treatment consisted of an abdominal total hysterectomy, bilateral salpingo-oophorectomy with or without pelvic lymph node dissection. Peritoneal cytology was obtained at laparotomy by peritoneal washing of the pouch of Douglas and was considered positive if malignant cells could be detected regardless of the number of malignant cells present. Disease-free survival (DFS) was considered the primary statistical endpoint. In 13/369 (3.5%) patients, positive peritoneal cytology was found. The median follow-up was 29 months and 15 recurrences occurred. Peritoneal cytology was independent of the depth of myometrial invasion and the grade of tumour differentiation, Patients with negative washings had a DFS of 96'7e at 36 months compared with 67% for patients with positive washings (log-rank P < 0.001). The presence of positive peritoneal cytology in patients with clinically stage I endometrioid adenocarcinoma of the endometrium is considered an adverse prognostic factor. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.

A novel target-field method for finite-length magnetic resonance shim coils: I. Zonal shims

This paper presents a new approach for the design of genuinely finite-length shim and gradient coils, intended for use in magnetic resonance imaging equipment. A cylindrical target region is located asymmetrically, at an arbitrary position within a coil of finite length. A desired target field is specified on the surface of that region, and a method is given that enables winding patterns on the surface of the coil to be designed, to produce the desired field at the inner target region. The method uses a minimization technique combined with regularization, to find the current density on the surface of the coil. The method is illustrated for linear, quadratic and cubic magnetic target fields located asymmetrically within a finite-length coil.