Anti-FcαRI Monoclonal Antibodies Resolve IgA Autoantibody-Mediated Disease.

Immunoglobulin A (IgA) is generally considered as a non-inflammatory regulator of mucosal immunity, and its importance in diversifying the gut microbiota is increasingly appreciated. IgA autoantibodies have been found in several autoimmune or chronic inflammatory diseases, but their role in pathophysiology is ill-understood. IgA can interact with the Fc receptor FcαRI on immune cells. We now established a novel IgA autoimmune blistering model, which closely resembles the human disease linear IgA bullous disease (LABD) by using genetically modified mice that produce human IgA and express human FcαRI. Intravital microscopy demonstrated that presence of IgA anti-collagen XVII, - the auto-antigen in LABD-, resulted in neutrophil activation and extravasation from blood vessels into skin tissue. Continued exposure to anti-collagen XVII IgA led to massive neutrophil accumulation, severe tissue damage and blister formation. Importantly, treatment with anti-FcαRI monoclonal antibodies not only prevented disease, but was also able to resolve existing inflammation and tissue damage. Collectively, our data reveal a novel role of neutrophil FcαRI in IgA autoantibody-mediated disease and identify FcαRI as promising new therapeutic target to resolve chronic inflammation and tissue damage.

Inadequacy of iridium implant as sole radiation treatment for operable breast cancer.

In order to avoid a prolonged course of external irradiation as part of breast conservation therapy, 27 patients received an iridium implant to the primary tumour bed as sole radiation treatment. Surgery was standardised comprising tumourectomy and axillary clearance. Using a rigid implant afterloading with iridium192 wires, 55 Gy was delivered on a continuous basis over 5 days. After 6 years median follow-up, relapse of cancer within the treated breast has occurred in 10 of the 27 patients (37%). Compared with historical controls treated by similar surgery and iridium192 implant (20 Gy) with external radiotherapy (46 Gy), there was a significantly increased breast relapse rate in those treated by iridium implant alone. However, the incidence of distant metastases and overall survival was similar. Thus, a continuous iridium192 implant delivering 55 Gy in 5 days is not an effective means of achieving local control in patients with operable breast cancer.

Influence of the oestrous cycle on experimental intrauterine E. coli infection in the sow.

The influence of the oestrous cycle on the onset of endometritis in the sow was studied. Ten pubertal, unmated gilts of the Belgian Negative Landrace were used. Nine gilts were inoculated into the uterus by laparotomy with a suspension of an E. coli strain isolated from the uterus of a discharging sow from a herd having many problems with vaginal discharge and a lowered fertility. One gilt was as a control inoculated with 2 ml of a PBS-solution. All sows inoculated during dioestrus developed clinical symptoms, but only 1 of the 5 gilts inoculated at standing oestrus developed a vaginal discharge. These data confirm the hypothesis that the stage of the oestrous cycle has an important influence on the onset of endometritis. The resistance to E. coli infections was higher when the gilts were inoculated during oestrus.

Water-sealed spirometer for measurements in newborns and infants.

Details are given of two spirometers for use in neonates and infants < 12 mo old. The minimum volumes are 520 and 670 ml, respectively. The maximum volume changes that can be recorded are 250 and 450 ml, respectively. The minimal detectable volume changes are 0.4 and 0.6 ml, respectively. Rebreathing of dead space gas is prevented by a fan producing a flow of 6.2 and 10.2 l/min, respectively; 100% gas mixing after injecting a gas bolus in the two spirometers is achieved in 5.7 and 6.6 s, respectively. Resistance to airflow is 0.2 kPa.l-1.s (2 cmH2O.l-1.s) at 150 ml/s in both spirometers. The frequency response of both instruments is flat to 6 cycles/s. The instruments can be easily cleaned and are suitable for bedside measurements.

Cerebral and aortic blood flow velocity patterns in preterm infants receiving prophylactic surfactant treatment.

Blood velocity in the internal carotid artery (ICA) and in the descending thoracic aorta (DAo) was investigated used Duplex-Doppler ultrasound in 14 infants of less than 30 weeks gestation, treated prophylactically with surfactant, and in 11 comparable infants with relatively mature lungs who served as controls. After surfactant administration, blood gases, pH or FiO2 were not different between the groups. Temporal mean blood velocity in the ICA was used as a relative measure of cerebral flow (TMFV-cer), and its coefficient of variation (CV-cer) was used to assess fluctuations in cerebral blood velocity. The pulsatility index (PI) in the ICA (PI-cer) and DAo (PI-DAo) was used to estimate if a left-to-right shunt was present. During surfactant instillation TMFV-cer was abnormally low and CV-cer indicated a fluctuating cerebral blood velocity. At 10 min after surfactant administration, TMFV-cer of the treated infants was higher compared to the controls, while CV-cer was stable in both groups. PI-cer and PI-DAo were abnormally high during the first hour of life after surfactant treatment, suggesting a left-to-right shunt without, however, clinical signs of a hemodynamically important ductus arteriosus. We suggest that cerebral perfusion is affected during and at 10 min after surfactant instillation. Left-to-right shunting appears to be a common event following surfactant treatment.

Replication of human occlusal tooth attrition surfaces for scanning electron microscopic study.

Silicone negative replicas of dentine islands exposed by occlusal attrition were examined on extracted human teeth using the scanning electron microscope. Because the details of the dentinal tubules were reproducible on the silicone impression, the replication technique was applied in vivo to occlusal attrition to demonstrate patent dentinal tubules in cases with symptomatic exposed dentine islands. using this replication technique, it should be possible to monitor the effect of the therapeutic management of symptomatic tooth attrition on dentinal tubule closure.

Iridium implant treatment without external radiotherapy for operable breast cancer: a pilot study.

A pilot study has been conducted to examine a new approach to the treatment of operable breast carcinoma. 27 patients with tumours measuring up to 4 cm in diameter have been treated by tumourectomy, axillary clearance and high dose iridium-192 implant (55 Gy) without any external beam radiotherapy. This enabled the entire local primary treatment of the breast carcinoma to be given in five days. The technique was compatible with adjuvant chemotherapy for those with involved axillary nodes. Local complications have been few and locoregional control has to date been satisfactory. With a relatively short median follow-up of 27 months, cosmesis was objectively rated as good or excellent in over 80% of cases and subjectively rated good/excellent in 96%. High dose brachytherapy now requires testing in a prospective clinical trial to determine whether it is as effective as standard breast conservation techniques for management of early breast cancer.

Influence of radiotherapy on the dose of adjuvant chemotherapy in early breast cancer.

399 patients with early breast cancer were randomly allocated to treatment by either modified radical mastectomy or lumpectomy and radiotherapy. 169 had histologically involved axillary nodes and were randomised to receive either adjuvant cytotoxic chemotherapy (76 patients) or no systemic adjuvant treatment (93 patients). Chemotherapy comprised a combination of oral cyclophosphamide and intravenous methotrexate and 5-fluorouracil (CMF) for 12 cycles over one year. Patients in the mastectomy group received a significantly higher percentage of the planned chemotherapy dose compared with those in the radiotherapy group (median 85% v. 71% p less than 0.05). Patients treated with radiotherapy were more frequently nauseated and developed more severe alopecia, but these differences were not statistically significant. At median follow-up of 37 months the relapse-rate and pattern of relapse were similar in both groups of patients receiving CMF.

Prednisolone improves the response to primary endocrine treatment for advanced breast cancer.

Two hundred and twenty patients with progressive advanced breast cancer were given primary endocrine treatment (PET) according to menstrual status. Pre-menopausal patients received ovarian irradiation (O) and post-menopausal tamoxifen 10 mg bd (T). Patients were randomised to receive either no additional treatment or prednisolone 5 mg bd (P). Similar results were observed in each menstrual subgroup. In 194 evaluable patients, the response to PET + P was 49% and to PET alone 30% (P less than 0.01). P increased the median duration of response from 9 to 14 months (P less than 0.002) and the median time to disease progression from 5 to 9 months (P less than 0.001). Response to P after O or T alone occurred in only 2/62 (3%). Median survival in patients randomised to receive P at the outset of PET was prolonged by 4 months (P less than 0.05). The addition of P significantly improves the response to O or T in the treatment of advanced breast cancer.

The relationship between intestinal Campylobacter species isolated from animals and humans as determined by BRENDA.

Intestinal thermophilic Campylobacter species produce stable patterns when subjected to bacterial restriction endonuclease DNA analysis (BRENDA); this technique is therefore of considerable value in epidemiological studies. BRENDA was used to examine thermophilic Campylobacter species from humans, wild and domestic animals. One hundred and ninety-four (61%) of 316 isolates of Campylobacter jejuni from humans had BRENDA patterns which could be matched to those of animal isolates. Poultry appear to be a major source of infection for C. jejuni in humans with nearly half (49.7%) of the human isolates giving patterns which were indistinguishable from those isolated from poultry. A total of 60 BRENDA types were identified from 316 human isolates and 11 of these had the same pattern as those isolated from poultry. One of the three Campylobacter coli BRENDA types recovered from poultry was indistinguishable from a human isolate type. Pigs appear to be only a minor source of C. coli infection for humans in New Zealand. Rats were found to be infected with strains of C. jejuni with BRENDA patterns indistinguishable from those infecting humans, poultry and a horse. None of the 102 isolates of Campylobacter species from wild birds gave BRENDA patterns similar to those of isolates from humans.

Restriction endonuclease analysis of Leptospira interrogans serovar hardjo isolates from cattle.

The genomes of 253 strains of Leptospira interrogans serovar hardjo were examined by restriction endonuclease analysis of their DNA. The strains had been isolated from cattle at an abattoir (190), milk of agalactic cows (seven) and from aborted bovine fetuses (56). Two distinct genome types, Hardjoprajitno and Hardjobovis, were detected. The majority (91 per cent) of isolates from abattoir cattle were of the Hardjobovis type while most (76 per cent) of the isolates from clinical/pathological material were similar to Hardjoprajitno.

Assessment of skin dose and its relation to cosmesis in the conservative treatment of early breast cancer.

A conservation technique has been developed for the treatment of early breast cancer which involved removal of the tumor, axillary clearance, tumor site implantation with Iridium-192 wires for a boost dose and subsequent treatment of the breast with radical megavoltage external beam therapy. Although the cosmetic results were satisfactory in the majority of the patients, for some it was rated as fair or poor. One variable factor which could have carried some morbidity was the dose of radiation received by the skin. In 51 patients, doses were measured at several points over the treated breast using Thermoluminescent Dosimetry (TLD) at the time of the iridium implant and during the subsequent external beam therapy. Development of skin pigmentation, oedema, and fibrosis were unrelated to the dose received by the skin but the findings suggested that doses greater than 50 Gy to the skin increased the possibility of late (greater than 24 months) telangiectasia over the boosted area. Treatment of tumors in the lower half of the breast, or in large breasts, was associated with a higher incidence of poor cosmesis. This may have been the result of varying posture on the interstitial dose distribution from the Iridium-192 wires and comparison of dose distribution in both supine and erect positions was carried out.

A comparison of serotyping, BRENDA-typing and incompatibility grouping, and toxin testing of haemolytic Escherichia coli isolated from piglets before and after weaning.

Before weaning, some young pigs in a research piggery excreted in their faeces a weakly haemolytic non-enterotoxigenic serotype of Escherichia Coli. After weaning, all of the pigs excreted strongly haemolytic Escherichia coli of known enteropathogenic serotypes (0-138 and 0-139). The 0-138 serotype produced vero cell toxin, whilst the 0-139 serotype elaborated heat labile enterotoxin. Haemolytic enterotoxigenic E. Coli were also recovered from three-week-old unweaned piglets with so-called ;milk scours; and from pigs with post-weaning diarrhoea on two local commercial piggeries. Selected haemolytic isolates were compared using serotyping, bacterial restriction endonuclease DNA analysis (BRENDA) and incompatibility grouping. The three typing methods divided most of the isolates into the same groupings; the exceptions were two isolates with the same BRENDA pattern and incompatibility group, but with different H-serotypes, and eleven isolates with the same serotype and BRENDA pattern but which showed differences in colony compatibility such that they were divided into five subgroups of a single incompatibility type.

Dual infections of red deer (Cervus elaphus) by Leptospira interrogans serovars copenhageni and hardjo.

On a property in the Nelson District, blood and urine samples were taken from red deer (Cervus elaphus) from which low (<1:100) antibody titres to serovar copenhageni and suspected leptospiral abortions had previously been reported. A total of 27 hinds were sampled. Microscopic agglutination test (MAT) titres in sera ranging from 1:32 to 1:128 were found in six animals. Thirteen leptospiral isolations were made from nine of the 27 urine samples. Four of these were typed as copenhageni and nine as hardjo. Two cultures were prepared from each urine sample and hardjo and copenhageni were both isolated from single urine samples from two animals. None of the 27 deer had serum MAT titres at 1:32 or above to copenhageni.

Ceroid lipofuscinosis in sheep. I. Bis(monoacylglycero)phosphate, dolichol, ubiquinone, phospholipids, fatty acids, and fluorescence in liver lipopigment lipids.

The ceroid lipofuscinoses are inherited lysosomal diseases of children characterized by a fluorescent lipopigment stored in a variety of tissues. Defects in lipid metabolism or the control of lipid peroxidation have been postulated to explain their pathogenesis. In the present study, lipopigment was isolated from the liver of sheep affected with ceroid lipofuscinosis. It was 70% protein, the rest being mainly lipids. These were only one-sixth as fluorescent as total liver lipids, but contained a number of fluorophors. None were major components of the lipopigment or the postulated fluorescent product of lipid peroxidation. Lipopigment lipids included the lysosomal marker bis(monoacylglycero)phosphate that contained 42.9% linoleate and 16.5% linolenate. Lipopigment neutral lipids were dolichol, dolichyl esters, ubiquinone, free fatty acids, and cholesterol, indicative of a lysosomal origin of the lipopigment. Phosphatidylcholine, phosphatidylinositol, phosphatidylserine, and phosphatidylethanolamine were present in proportions and with fatty acid profiles typical of lysosomes. No differences were found between the lipids of total control and affected livers, nor the fatty acid profiles of their phosphatidylcholine, phosphatidylethanolamine, or triglycerides. It is concluded that ovine ceroid lipofuscinosis is not a lipidosis, nor does the lipopigment arise from the abnormal peroxidation of lipids. Strong similarities between the lipopigment and the age pigment lipofuscin were noted.

Differentiation of reference strains of leptospires of the Pomona serogroup by cross-agglutination absorption and restriction endonuclease analysis.

The serological classification of all reference strains that have been described as representing separate serovars of Leptospira interrogans within the Pomona serogroup was investigated using cross-agglutination absorption and bacterial restriction endonuclease analysis (BRENDA). Comparative cross-agglutination absorption studies indicated that cornelli CB, monjakov Monjakov and kennewicki LT1026 were homologous with pomona Pomona, and dania K1 and tsaratsova B81/7 were homologous with mozdok 5621. BRENDA confirmed these results, except that pomona Pomona and monjakov Monjakov showed a difference in the high molecular weight region. It is proposed that four serovars be currently recognised within the Pomona serogroup: pomona, mozdok, proechimys and tropica. The relative merits of the use of cross-agglutination absorption and BRENDA with respect to identification of Pomona serogroup isolates are discussed.

Identification by cross-agglutination absorption and restriction endonuclease analysis of leptospires of the Pomona serogroup isolated in the United Kingdom.

Five strains of Leptospira interrogans isolated in the United Kingdom and belonging to the Pomona serogroup were subjected to cross-agglutination absorption and bacterial restriction endonuclease DNA analysis (BRENDA) for their identification. British isolates were compared with reference strains representing the known serovars in the Pomona serogroup and also with isolates of the Pomona serogroup obtained from other countries. Three strains isolated from wildlife in England produced equivocal results when the cross-agglutination absorption and BRENDA results were compared. According to the World Health Organisation definition of a serovar the three English strains represented two new serovars, whereas by BRENDA all three had DNA electrophoresis patterns indistinguishable from serovar mozdok. Serovar pomona has not as yet been isolated in Great Britain and the epidemiology of the Pomona serogroup infections that have been detected by serology suggests that a serovar such as mozdok, maintained by wildlife, may be the causal agent. Two strains isolated in Northern Ireland were identified as pomona by the cross-agglutination absorption test. Further studies are needed to investigate the homogeneity of field and reference strains that are designated as pomona using the cross-agglutination absorption test.

Interstitial irradiation for squamous carcinoma of the oral cavity.

Interstitial radiation delivered by iridium 192 implants was used to treat 38 patients with squamous carcinoma of the oral cavity. Thirty-six patients had either T1 or T2 tumours and no patient had palpable nodes at the time of implantation. Control of the primary tumour was achieved in all but 2 patients; these 2 were successfully treated by surgery. Fifteen patients (39%) went on to develop metastatic neck nodes. Nine were cured by radical neck dissection but the remaining 6 died of their disease. This gives a 5-year actuarial survival of 81%. Since all deaths occurred after the development of metastatic disease in the neck with control of the primary lesion, the evidence for and against prophylactic treatment of the neck lymphatics in clinically negative necks was reviewed. Prophylactic irradiation of the neck is probably preferable to any form of neck dissection but clear evidence that this improves long-term survival compared with careful follow-up and radical neck dissection for palpable nodes is still lacking.