Biomedical subjects
Publications and source records attributed to D M Francis.
This paper reports an isolated case of the exceedingly rare cutaneo-skeletal condition craniomandibular dermatodysostosis, in which focal glomerular sclerosis and end-stage renal failure developed and renal transplantation was required.
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We have constructed an expression vector that leads to secretion of the whole Fc of human immunoglobulin E (hIgE-Fc) from mammalian cells at levels up to 100 mg/l of culture. Two surface glycosylation sites at Asn265 and Asn371 have been changed to glutamine, to obtain a more homogeneous preparation of hIgE-Fc for structural studies. Comparison of wild-type and mutant products revealed that Asn371 is rarely glycosylated in Chinese hamster ovary cells. Both the double mutant and wild-type hIgE-Fc bind to the high-affinity IgE receptor, Fc epsilon RI, with about the same affinity as myeloma IgE (Ka in the range 10(10)-10(11) M-1), and were able to sensitize isolated human basophils for anti-IgE triggering of histamine release. However, only the double mutant hIgE-Fc approached the affinity of myeloma IgE for the low-affinity receptor, Fc epsilon RII (Ka = 7.3 x 10(7) M-1), whereas the wild-type hIgE-Fc bound with a 10-fold lower affinity (Ka = 4.1 x 10(6) M-1).
Results of renal transplantation in very young children with end-stage chronic renal failure have been poor compared with those in older children and adults. Consequently small children either may not be treated or may be placed on chronic dialysis programmes. Between 1988 and 1992, six children under the age of 5 years received seven renal transplants at the Royal Children's Hospital, Parkville, Victoria, Australia; five from live donors and two from cadaver donors. All children were treated with peritoneal dialysis before transplantation, and immunosuppressed with a standardized regimen of cyclosporine, azathioprine and prednisolone. An extraperitoneal incision was used, and the donor renal vessels were anastomosed to the lower abdominal aorta and inferior vena cava or the common iliac vein. All children received intensive monitoring and fluid replacement during the peri-operative period. Patient survival was 100%. One cadaver graft failed 1 week after transplantation because of irreversible acute rejection. This child subsequently received a successful second transplant. Two children developed postoperative urinary fistulae which were treated successfully by further operation. Current renal function in all children is excellent. The success of this programme has led us to review our attitude towards renal transplantation in this age group and to advocate live donor renal transplantation as the treatment of choice in very young children with end-stage chronic renal failure whenever possible.
AIMS: To review the outcome of renal transplantation in small children treated with triple immunosuppression at a single Australian centre. METHODS: The medical records of all children under the age of five years undergoing renal transplantation from 1988 were reviewed. The duration of follow-up was 30 months (range 18-36). RESULTS: Six children received seven renal allografts (five living-related [LR] and two cadaveric [CD]). They had a median age of 3.75 years (range 1.5-4.9) and weight of 11.6 kg (9.1-14.5) at the time of transplantation. All patients received an immunosuppressive regime involving cyclosporin A, azathioprine and prednisolone. There were no deaths. The only graft lost was a CD graft (severe acute rejection within one week of transplantation). Hypertension occurred in all recipients and usually required more than one antihypertensive drug for treatment. Renal function measured by serum median creatinine concentration (range) was 0.05 mmol/L (0.03-0.11) at three months (n = 6) and 0.10 mmol/L (0.07-0.22) at 30 months (n = 4). Growth estimated from median (range) height standard deviation scores was -1.97 (-1.36-(-4.04)) at three months (n = 6) and -1.90 (-1.74-2.50) at 30 months (n = 4). No patient was entirely weaned from prednisolone. Cyclosporin A side effects included hirsutism (five patients), gingival hyperplasia (six patients) and nephrotoxicity (three patients). CONCLUSIONS: Satisfactory patient and graft survival can be accomplished in this recipient age group. The results compare with other international experience and accumulating Australian experience. Hypertension and poor skeletal growth were consistent observations. The long-term outcome of renal function using triple immunosuppression remains to be determined.
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Thirty-four children (< or = 15 years of age) with end-stage renal failure received 39 renal allografts between 1985 and 1991 and were treated with cyclosporin A (CyA), azathioprine and low-dose prednisolone (PNL). We aimed to withdraw PNL by 6 months after transplantation. Median duration of follow-up was 2 years 4 months (range 0.1 month to 6 years 4 months). There were no deaths. Crude graft survival for living-related grafts (n = 9) was 100%, although only 1 patient has been followed for > 2 years. For cadaveric grafts (n = 30), 1- and 5-year actuarial graft survivals were 90% and 79% respectively. At 12 months posttransplant, the median (range) glomerular filtration rate for all patients was 63 (19-109) ml/min per 1.73 m2 (n = 25) and at 5 years was 48 (17-64) ml/min per 1.73 m2 (n = 9). Complications observed included rejection episodes which occurred after discontinuation of PNL. Long-term (after 12 months), 28% of patients remain on PNL. Hypertension was present in more than 50% of patients. Severe CyA nephrotoxicity was not seen. Catch-up growth as determined by the change (delta) in mean height standard deviation score (Ht-SDS) was noted at 1 year [delta SDS/year = +0.60; P < 0.001 (n = 18)] and at 2 years [delta SDS/year = +0.27; P < 0.01 (n = 16)] in pre-pubertal patients. The median Ht-SDS at 2 years for pre-pubertal children was -0.71 SD and growth velocity did not improve thereafter.(ABSTRACT TRUNCATED AT 250 WORDS)
A segment of DNA 5' to the transcribed region of an auxin-regulated gene, ARPI, from Lycopersicon esculentum Mill. cv. VFN8 contains a sequence with the structural characteristics of a transposable element. The putative element (Lyt1) is 1340 bp long, has terminal inverted repeats of approximately 235 bp and is flanked by 9-bp direct repeats. Lyt1 has a structure similar to the Robertson's Mutator (Mu) family from maize. The terminal inverted repeats are 80% AT-rich, are 96.6% identical, and define a larger family of repetitive elements. Southern analysis and genomic dot-blot reconstructions detected at least 41 copies of Lyt1-hybridizing sequences in red-fruited Lycopersicon spp. (L. esculentum, L. pimpinellifolium and L. cheesmanii), and 2-8 copies in the green-fruited species (L. hirsutum, L. pennellii, L. peruvianum, L. chilense and L. chmielewskii). There were two to four copies in the Solanum spp. closely allied with the genus Lycopersicon (S. lycopersicoides, S. ochranthum and S. juglandifolium), while the more distantly related Solanum spp. showed little (one to two copies in S. tuberosum) to no (S. quitoense) detectable hybridization under stringent conditions. Linkage analysis in the F2 progeny of a cross between L. esculentum and L. cheesmanii indicated that at least six loci that hybridize to the Lyt1 sequence are dispersed in the genome. Polymerase chain reaction and Southern analyses revealed that some red-fruited accessions and L. chmielewskii lacked Lyt1 5' to the transcribed region of ARPI. Subsequent sequence analysis indicated that only one copy of the 9-bp direct repeat (target site) was present, suggesting that transposition of the element into the ARPI gene occurred after the divergence of the red-fruited and green-fruited Lycopersicon species.
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AIM: To investigate the tissue specificity of a novel monoclonal antibody raised to a tissue fraction of normal human liver and which identified certain cells of gastric and duodenal mucosa. METHODS: A total of 155 samples of various tissues obtained from 100 surgical specimens were fixed in cold ethanol-paraformaldehyde, embedded in paraffin wax, and 3 microns sections were studied by immunohistochemical and lectin staining procedures. RESULTS: Immunohistochemical staining showed a major tissue specific component which was strongly expressed by mucous neck cells of the body of the stomach, glands of the cardia and pyloric antrum, and by Brunner's glands. Staining for antigen in the periductal glands of normal major biliary and pancreatic ducts was variable and relatively weaker. It was not detected elsewhere in normal intestine or in the other normal tissues tested. Barrett's mucosa of gastric cardia type, and pyloric gland metaplasia in the gall bladder and small bowel affected with Crohn's disease stained for the antigen. The tissue distribution of the antigen was identical with that of a glycoprotein, demonstrated by an induced affinity for concanavalin A following treatment of tissue sections with periodic acid. The antigen was not sensitive to sialidase. CONCLUSIONS: The tissue component identified (designated here as antigen D10) seems to be characteristic of certain differentiated epithelial cells derived from that part of foregut giving rise to stomach, duodenum, and biliary and pancreatic ducts. The antibody will be of use in investigating pathological processes involving tissue differentiation at these sites, and in the oesophagus and intestines.
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BACKGROUND: Most urticarias are induced by vasoactive mediators such as histamine released from mast cells. Although mast cells are activated by allergens through cross-linking of cell-surface--bound IgE, this mechanism does not appear to explain most cases of chronic urticaria, which, when allergic, infectious, drug-induced, or physical causes cannot be identified, are classified as idiopathic. METHODS: We recruited 26 patients with chronic idiopathic urticaria, in whom intradermal injection of autologous serum caused a wheal-and-flare response. Serum from four patients that induced marked histamine release from basophils from a donor with very low serum IgE levels was studied with respect to the IgE dependence of the histamine release, the activity of the IgG fractions, and the neutralizing effect of a recombinant preparation of the soluble extracellular domain of the alpha subunit of the high-affinity IgE receptor (sFc epsilon RI alpha). RESULTS: The histamine-releasing activity of the serum was abolished by passive sensitization of basophils with myeloma IgE, enhanced after dissociation of IgE by treatment with lactic acid, and induced by IgG fractions from the serum of all four patients. Preincubation of the serum and isolated IgG with sFc epsilon RI alpha resulted in almost complete neutralization. CONCLUSIONS: Histamine-releasing IgG autoantibodies against the alpha subunit of the high-affinity IgE receptor are present in the circulation of some patients with chronic urticaria. Autoantibody-induced cross-linking of IgE receptors may be an important mechanism in the pathogenesis of chronic urticaria and other diseases mediated by mast cells.
OBJECTIVE: To estimate the potential increase in renal donation rates if elderly donors (those over 60 years of age) were considered. DESIGN: Patients dying from acute brain damage resulting from stroke were identified using the Royal Melbourne Hospital (RMH) Stroke Service Register. Their records were retrospectively analysed to assess their eligibility as potential renal donors. SETTING: One hundred and ninety-eight patients dying from acute brain damage caused by stroke at a large metropolitan teaching hospital (RMH), from May 1987 to December 1990 inclusive. PATIENT ASSESSMENT: Patients were considered "eligible", "ineligible" or "possibly eligible" (requiring further assessment) as donors according to existing strict criteria (see methods) but irrespective of age. RESULTS: Of 198 stroke patients dying of brain damage, 92 satisfied the criteria of eligibility for renal donation; 51 of these were over 60 years old, yet only one became a renal donor. CONCLUSION: There is good evidence that elderly donors are acceptable for renal transplantation, yet they are not being referred. The consideration of elderly stroke victims as renal donors could have a dramatic effect on decreasing transplant waiting lists, increasing recipient patient well-being, and reducing hospital costs.
OBJECTIVE: To determine the outcome of patients with end-stage chronic renal failure treated by live donor renal transplantation at the Royal Melbourne Hospital and Royal Children's Hospital between 1973 and 1991, during which time two distinct immunosuppressive regimens were used. DESIGN: Data about live donor renal transplant recipients were retrieved from the Australian and New Zealand Dialysis and Transplantation Association Registry, to which we have submitted data on all transplant recipients at six monthly intervals since the commencement of our dialysis and transplant programs. PATIENTS: Seventy-two patients with chronic renal failure who received live donor renal transplants during the 19 years from February 1973 to February 1992 were included. MAIN OUTCOME MEASURES: Patient survival, transplant survival, transplant function, change in prednisolone requirements, and duration of hospital stay. RESULTS: The first 32 patients were treated with immunosuppressive regimens based on combinations of prednisolone and azathioprine ("dual therapy"), while the next 40 patients were treated with combinations of cyclosporin, prednisolone and azathioprine ("triple therapy"). Survival of patients in each group five years after transplantation was 97%. Actuarial graft survival at 5, 10 and 15 years in the dual therapy group was 58%, 52% and 47%, compared with a 5-year actuarial graft survival in the triple therapy group of 96%. There was no statistically significant difference in renal transplant function between the two groups within the first 6 years after transplantation. Twelve of 26 patients (46%) treated initially with triple therapy were able to stop treatment with prednisolone within 12 months of transplantation. Median hospital stay was 12 (range, 6-35) days during the period 1973-1985 and 8 (range, 5-20) days for the 1985-1992 period. CONCLUSION: Live donor renal transplantation has provided a highly satisfactory means of treating patients with end-stage chronic renal failure in the short and long term. Our recent experience indicates that excellent patient and graft survival and adequate renal function can be achieved by treating live donor renal transplant recipients with a triple immunosuppressive regimen of low dose cyclosporin, prednisolone and azathioprine.
Blood transfusion prior to renal transplantation improves subsequent renal allograft survival, and some experimental studies have shown that allogeneic transfusion significantly increases growth of subsequently transplanted tumors. The aim of the present study was to examine the influence of the timing of transfusion on tumor growth. Six experiments were performed, each with different intervals between blood transfusion and inoculation of mice with an immunogenic B16 melanoma cell line. Each experiment contained three groups of C57 BL/6J mice which received intravenously normal saline, syngeneic blood, or allogeneic blood. Allogeneic transfusion 7 and 10 days before, but not at the time of, tumor inoculation produced a significant increase in tumor growth. Allogeneic transfusion within the first 10 days after tumor inoculation was associated with larger and heavier tumors than those observed in animals treated with saline or syngeneic blood, although the differences were not always statistically significant. Multiple transfusions after tumor inoculation and transfusions in animals bearing well-established tumors significantly increased tumor growth. The study shows that growth of a transplantable immunogenic murine tumor can be increased by prior allogeneic transfusion and, perhaps more importantly, by allogeneic transfusions given after the tumor has become established.
Pyeloureterostomy is the standard procedure for reconstructing renal allograft ureteral complications. Most reports describe an end-to-end technique with or without native nephrectomy. An alternative is an end-to-side anastomosis, leaving the native ureter in continuity. We report our experience with the latter method. Since July 1983, 437 renal transplantations have been performed at our institution. End-to-side pyeloureterostomy has been used in 5 cases for urological reconstruction after renal transplantation following ureteral ischemic necrosis or stenosis. In 1 patient the native kidneys had been removed several years previously but in the remaining 4 the native kidneys were left in situ. There have been no significant complications following this procedure. We believe that by not significantly mobilizing, ligating or dividing the native ureter the chance of anastomotic breakdown due to ischemia may be decreased.
This paper prospectively evaluates 33 dual lumen, right atrial catheters inserted into either an external or internal jugular vein by open operation in 29 patients, of whom 15 required haemodialysis and 14 required temporary plasma exchange. The median (range) catheter survival in the haemodialysis and plasma exchange groups was 108 days (7-334 days) and 61 days (10-116 days), respectively. Life table analysis demonstrated that overall catheter survival was 58% at 200 days. The main causes of catheter failure were infection (four cases), poor flow (three cases) and accidental removal (one case). Another nine catheters were removed electively because of maturation of alternative methods of vascular access (five cases), completion of plasma exchange treatment (three cases), or successful renal transplantation (one case). Long-term silastic catheters, inserted into the right atrium via a jugular vein, have distinct advantages over temporary subclavian vein catheters and external arteriovenous (AV) shunts; this form of access is the method of choice for haemodialysis and plasma exchange patients who require immediate and short- to medium-term vascular access.