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.

The use of perineal ultrasound to quantify levator activity and teach pelvic floor muscle exercises

Perineal ultrasound was used to detect and quantify levator activity by measuring the displacement of the internal urethral meatus against the inferoposterior margin of the symphysis pubis, Women who had previously been instructed in pelvic floor muscle exercises were more likely to contract the levator muscle when asked to do so than were those without previous instruction (P

The influence of posture on perineal ultrasound imaging parameters

A prospective clinical study was carried out to evaluate the influence of posture on perineal ultrasound imaging parameters. One hundred and thirty-two consecutive women presenting with symptoms of lower urinary tract dysfunction were examined by multichannel videourodynamics and perineal ultrasound, both supine and standing. Ultrasound included color Doppler imaging when available, i.e. in a subgroup of 99 patients. The position of the bladder neck at rest was higher in the supine position (P

The urethral pressure profile and ultrasound imaging of the lower urinary tract

In a prospective study 105 patients with symptoms of stress incontinence underwent video-urodynamic testing, including resting urethral pressure profilometry and translabial ultrasound. The urethral pressure profile (UPP) included maximum urethral closure pressure (MUCP), functional length (FL) and area under the curve (AUC). Ultrasound parameters included urethral thickness, urethral rotation and bladder neck descent, as well as funneling/opening of the internal urethral meatus on Valsalva maneuver. Levator contraction strength was assessed measuring the cranioventral displacement of the internal meatus. Negative correlations between UPP data and age, parity and previous surgery were observed which were consistent with literature data. There was a positive correlation :between the urethral AP diameter on ultrasound and the MUCP, which agrees with reports showing reduced sphincter thickness or volume in stress-incontinent women. Hypermobility on ultrasound did not correlate with UPP data. However, a lower MUCP correlated with extensive opening of the bladder neck. Finally, there was a trend towards poorer pelvic floor function with lower MUCP measurements.

Immune responses to ISCOM (R) formulations in animal and primate models

ISCOMs(R) are typically 40 nm cage-like structures comprising antigen, saponin, cholesterol and phospholipid. ISCOMs(R) have been shown to induce antibody responses and activate T helper cells and cyrolytic T lymphocytes in a number of animal species, including non-human primates. Recent clinical studies have demonstrated that ISCOMs(R) are also able to induce antibody and cellular immune responses in humans. This review describes the current understanding of the ability of ISCOMs(R) to induce immune responses and the mechanisms underlying this property. Recent progress in the characterisation and manufacture of ISCOMs(R) will also be discussed. (C) 2001 Elsevier Science Ltd. All rights reserved.

Minimum acceptable standards for digital compression of a fetal ultrasound video-clip

If the Internet could be used as a method of transmitting ultrasound images taken in the field quickly and effectively, it would bring tertiary consultation to even extremely remote centres. The aim of the study was to evaluate the maximum degree of compression of fetal ultrasound video-recordings that would not compromise signal quality. A digital fetal ultrasound videorecording of 90 s was produced, resulting in a file size of 512 MByte. The file was compressed to 2, 5 and 10 MByte. The recordings were viewed by a panel of four experienced observers who were blinded to the compression ratio used. Using a simple seven-point scoring system, the observers rated the quality of the clip on 17 items. The maximum compression ratio that was considered clinically acceptable was found to be 1:50-1:100. This produced final file sizes of 5-10 MByte, corresponding to a screen size of 320 x 240 pixels, running at 15 frames/s. This study expands the possibilities for providing tertiary perinatal services to the wider community.

Realtime fetal ultrasound by telemedicine in Queensland. A successful venture?

We have established a realtime fetal tele-ultrasound consultation service in Queensland, which has been integrated into our routine clinical practice, The service, which uses ISDN transmission at 384 kbit/s, allows patients in Townsville to be examined by subspecialists in Brisbane, 1500 km away. For the 90 tele-ultrasound consultations performed for the first 71 patients, 90% of the babies have been delivered, and outcome data have been received on all the pregnancies. All significant anomalies and diagnoses have been confirmed. The referring clinicians would have physically referred 24 of the 71 patients to Brisbane in the absence of telemedicine. A crude cost-benefit calculation suggests that the tele-ultrasound service resulted in a net saving of A$6340, and at the same time enabled almost four times the number of consultations to be carried out.

Effect of restricted feed intake on early reproductive development in Large White gilts

Forty-five Large White gilts were used to study the effect of energy intake from 28 to 176 d of age on body composition and reproductive development. From 28 to 60 d, the gilts were fed ad libitum a 16.6 MJ DE/kg, 24% crude protein and 1.3% total lysine diet. From 61 d of age three dietary treatments were used; 1) ad libitum access to feed (15.6 MJ DE/kg, 21% crude protein and 1.07% total lysine) (H), 2) feed offered at 75% (M) of the previous days intake of H, and 3) feed offered at 60% (L) of the previous days intake of H. ADG from 61 to 176 d of age was (p <0.05) affected by treatment. Although live weight at 176 d of age did not differ (p >0.1) the H gilts had higher (p <0.08) carcass weights than the M or L gilts. Back fat depths were similar (p >0.1) for all treatments at 115 d of age, however by 176 d of age M and H gilts were fatter (p <0.1) than L gilts. The mean lipid deposition (LD) from 115 to 176 d of age for L gilts (78.9 g/d) was less (p <0.05) than for M gilts (143.6 g/d) and H gilts (135.6 g/d). There were no differences between treatments for protein deposition (PD) over the same period. More (p <0.05) H gilts (n=8) attained puberty (first observed estrus) than either M gilts or L gilts (n=4 for both). Follicle numbers were similar (p >0.1) across treatments. For gilts that attained puberty, H gilts had fewer (p <0.05) follicles (13.5) than M gilts (19.7) and L gilts (21.3). For gilts with follicular development, H gilts had the heaviest (458.7 g) reproductive tract weight (RTW). However, for those that attained puberty, L gilts had the heaviest RTW. RTW were lowest for those with no follicular development. Energy restriction had a negative impact on puberty attainment, i.e. it took longer to reach puberty. However, for gilts that attained puberty, the number of follicles was greater for those on lower feed intakes. It would appear that rate of fat deposition, but not necessarily the total amount of fat, plays an important role in puberty attainment.

N-15 natural abundance of fossil peat reflects the influence of animal-derived nitrogen on vegetation

delta(15)N signatures of fossil peat were used to interpret past ecosystem processes on tectonically active subantarctic Macquarie Island. By comparing past vegetation reconstructed from the fossil record with present-day vegetation analogues, our evidence strongly suggests that changes in the delta(15)N signatures of fossil peat at this location reflect mainly past changes in the proportion of plant nitrogen derived from animal sources. Associated with uplift above sea level over the past 8,500 years, fossil records in two peat deposits on the island chronicle a change from coastal vegetation with fur and elephant seal disturbance to the existing inland herbfield. Coupled with this change are synchronous changes in the delta(15)N signatures of peat layers. At two sites N-15-enriched peat delta(15)N signatures of up to +17parts per thousand were associated with a high abundance of pollen of the nitrophile Callitriche antarctica (Callitrichaceae). At one site fossil seal hair was also associated with enriched peat delta(15)N. Less N-15 enriched delta(15)N signatures (e.g. -1.9parts per thousand to +3.9parts per thousand) were measured in peat layers which lacked animal associated C. antarctica and Acaena spp. Interpretation of a third peat profile indicates continual occupation of a ridge site by burrowing petrels for most of the Holocene. We suggest that N-15 signatures of fossil peat remained relatively stable with time once deposited, providing a significant new tool for interpreting the palaeoecology.

Myocardial abnormalities in hypertensive patients with normal and abnormal left ventricular filling: a study of ultrasound tissue characterization and strain

Abnormal left ventricular (LV) filling is common, but not universal, in hypertensive LV hypertrophy (LVH). We sought to elucidate the relative contributions of myocardial structural changes, loading and hypertrophy to LV dysfunction in 113 patients: 85 with hypertensive LVH and 28 controls without LVH and with normal filling. Patients with normal dobutamine stress echocardiography and no history of coronary artery disease were selected, in order to exclude a contribution from ischaemia or scar. Abnormal LV filling was identified in 65 LVH patients, based on Doppler measurement of transmitral filling and annular velocities. All patients underwent grey-scale and colour tissue Doppler imaging from three apical views, which were stored and analysed off line. Integrated backscatter (113) and strain rate imaging were used to detect changes in structure and function; average cyclic variation of 113, strain rate and peak systolic strain were calculated by averaging each segment. Calibrated 113 intensity, corrected for pericardial 113 intensity, was measured in the septum and posterior wall from the parasternal long-axis view. Patients with LVH differed significantly from controls with respect to all backscatter and strain parameters, irrespective of the presence or absence of abnormal LV filling. LVH patients with and without abnormal LV filling differed with regard to age, LV mass and incidence of diabetes mellitus, but also showed significant differences in cyclic variation (P < 0.01), calibrated 113 in the posterior wall (P < 0.05) and strain rate (P < 0.01), although blood pressure, heart rate and LV systolic function were similar. Multivariate logistic regression analysis demonstrated that age, LV mass index and calibrated IB in the posterior wall were independent determinants of abnormal LV filling in patients with LVH. Thus structural and functional abnormalities can be detected in hypertensive patients with LVH with and without abnormal LV filling. In addition to age and LVH, structural (not functional) abnormalities are likely to contribute to abnormal LV filling, and may be an early sign of LV damage. 113 is useful for the detection of myocardial abnormalities in patients with hypertensive LVH.

A review of animal models for the study of arsenic carcinogenesis

As inorganic arsenic is a proven human carcinogen, significant effort has been made in recent decades in an attempt to understand arsenic carcinogenesis using animal models, including rodents (rats and mice) and larger mammals such as beagles and monkeys. Transgenic animals were also used to test the carcinogenic effect of arsenicals, but until recently all models had failed to mimic satisfactorily the actual mechanism of arsenic carcinogenicity. However, within the past decade successful animal models have been developed using the most common strains of mice or rats. Thus dimethylarsinic acid (DMA), an organic arsenic compound which is the major metabolite of inorganic arsenicals in mammals, has been proven to be tumorigenic in such animals. Reports of successful cancer induction in animals by inorganic arsenic (arsenite and arsenate) have been rare, and most carcinogenetic studies have used organic arsenicals such as DMA combined with other tumor initiators. Although such experiments used high concentrations. of arsenicals for the promotion of tumors, animal models using doses of arsenicals species closed to the exposure level of humans in endemic areas are obviously the most significant. Almost all researchers have used drinking water or food as the pathway for the development of animal model test systems in order to mimic chronic arsenic poisoning in humans; such pathways seem more likely to achieve desirable results. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

Effect of periparturient diseases accompanied by excessive vulval discharge and weaning to mating interval on sow reproductive performance

Objective To evaluate the effect of periparturient disease accompanied by vulval discharge, and weaning-to-mating intervals, on sow fertility and litter size. Design Reproductive data were collected and analysed from 19 Hungarian swine herds over a 4 year period. Conception rates, farrowing rates and litter sizes of sows with periparturient disease accompanied by vulval discharge were used to evaluate the relationship between duration of vulval discharge and subsequent fertility and litter size. The possibility of interactions between weaning-to-mating intervals and duration of vulval discharges was investigated to determine if there was any effect on subsequent fertility and litter size. Results and conclusions Both parity 1 and parity 2 to 8 sows having had periparturient disease accompanied by vulval discharge in excess of 6 days duration had significantly (P < 0.001) lower subsequent fertility (conception, farrowing and adjusted farrowing rates) compared with sows of similar parity where the duration of vulval discharge was < 4 or 4 to 6 days. There was no difference in fertility rates between sows, in both parity categories, with vulval discharge for < 4 days compared with 4 to 6 days. A duration of vulval discharge in excess of 6 days in parity 1 sows significantly reduced litter size (total born and live-born) in subsequent farrowings, but not in parity 2 to 8 sows. There was no interaction between the duration of vulval discharge and post-weaning to mating intervals. However sows with weaning to mating intervals between 7 and 10 days had smaller (P < 0.001) subsequent litter sizes compared with 3 to 6 or 11 to 14 day intervals. It was concluded that the duration of vulval discharge in excess of 6 days was an indication of a severe persistent endometritis adversely affecting fertility of sows.

Dynamin-dependent endocytosis is necessary for convergent-extension movements in Xenopus animal cap explants

Cadherin cell-cell adhesion molecules are important determinants of morphogenesis and tissue patterning. C-cadherin plays a key role in the cell-upon-cell movements seen during Xenopus gastrulation. In particular, regulated changes in C-cadherin adhesion critically influence convergence-extension movements, thereby determining organization of the body plan. It is also predicted that remodelling of cadherin adhesive contacts is important for such cell-on-cell movements to occur. The recent demonstration that Epithelial (E-) cadherin is capable of undergoing endocytic trafficking to and from the cell surface presents a potential mechanism for rapid remodelling of such adhesive contacts. To test the potential role for C-cadherin endocytosis during convergence-extension, we expressed in early Xenopus embryos a dominantly-inhibitory mutant of the GTPase, dynamin, a key regulator of clathrin-mediated endocytosis. We report that this dynamin mutant significantly blocked the elongation of animal cap explants in response to activin, accompanied by inhibition of C-cadherin endocytosis. We propose that dynamin-dependent endocytosis of C-cadherin plays an important role in remodelling adhesive contacts during convergence-extension movements in the early Xenopus embryo.