Antineutrophilic cytoplasmic antibodies in systemic vasculitis.
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Autoantibodies↗
Biomedical subjects
B F Murphy
Publications and source records attributed to B F Murphy.
Human seminal clusterin (SP-40,40). Isolation and characterization.
Molecular cloning of the human complement inhibitor SP-40,40, has revealed strong homology to a major rat and ram Sertoli cell product, sulfated glycoprotein-2, known also as clusterin. This study reports the purification and characterization of human seminal clusterin. Two-dimensional gel electrophoresis revealed charge differences between clusterin purified from semen and the serum-derived material. Both preparations demonstrate comparable hemagglutination (clustering) activity and inhibition of C5b-6 initiated hemolysis. The average clusterin concentration in normal seminal plasma is considerably higher than that found in serum. Mean seminal plasma clusterin concentrations were significantly lower in azoospermia caused by obstruction or seminiferous tubule failure than with oligospermia or normospermia. Only men with vasal agenesis had undetectable seminal clusterin, suggesting that some of the seminal clusterin is produced by the seminal vesicles. Immunofluorescence of human spermatozoa revealed that clusterin was detected on 10% of spermatozoa, predominantly those that were immature or had abnormal morphology. A pilot study of 25 patients suggests that seminal clusterin concentration, together with sperm motility and morphology, is correlated with the fertilization rate in vitro. The function of seminal clusterin is unknown. Its extensive distribution in the male genital tract and its high concentration in seminal plasma suggests an important role in male fertility.
Animals↗
Antineutrophil cytoplasm antibody (ANCA) associated vasculitis.
In 1982 we first reported the presence of antineutrophil cytoplasm antibodies (ANCA) in 8 patients with systemic vasculitis and segmental necrotizing glomerulonephritis. The results of long-term follow-up are described. Screening of 7,500 serum samples revealed positive ANCA in 9 additional patients with vasculitis. Eighty-eight other patients with vasculitis were ANCA negative, including 7 with microscopic polyarteritis nodosa (MPAN) and 8 with Wegener's granulomatosis (WG). Conversely, ANCA were never detected in the absence of vasculitis. Fourteen patients presenting with glomerulonephritis and ANCA were followed for a median of 6.3 years. Eleven patients had MPAN and 3 WG. Remissions were obtained with immunosuppressive therapy in all patients. Clinical relapse was associated with the reappearance of ANCA. Five-year survival was 89% and 5-year dialysis free survival was 77%. ANCA are specific markers for a sub-group of patients with vasculitis and are sensitive markers of disease activity. Glomerulonephritis associated with ANCA positive vasculitis has a favorable outcome with immunosuppressive therapy.
Antibodies, Antinuclear↗
Migratory polyarthralgia and haemoptysis.
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Granulomatosis with Polyangiitis↗
Abdominal positioning interneurons in crayfish: participation in behavioral acts.
Premotor interneurons involved in the abdominal positioning behaviors of the crayfish, Procambarus clarkii, were studied intracellularly, along with motoneuron activity, in semi-intact preparations during episodes of fictive behavior. Each impaled cell was tested by injecting depolarizing current and examining the motor output. If a response was evoked then the cell was classified as a flexion-producing interneuron (FPI), extension-producing interneuron (EPI) or mixed output interneuron (MOI). A platform drop/rise procedure was then used to elicit abdominal extension-like and flexion-like responses. Interneurons that were active during positioning behavior were silenced by hyperpolarization to determine their contribution in generating the underlying motor program. The data were used to assess the degree of participation of these interneurons in abdominal positioning behavior. Fewer than half of the FPIs, EPIs and MOIs became active during the behavioral episodes. Strength of response to depolarizing current was not correlated with the probability that a cell would fire during behavior. Hyperpolarization tests showed that typical FPIs, EPIs and MOIs were only responsible for a small part of the overall motor output. Also, interneurons, regardless of their FPI or EPI classification, were often observed to fire during both flexion-like and extension-like behaviors. Responses of FPIs, EPIs and MOIs to repeated platform movements suggest that these cells may fire according to a probability distribution depending on: (1) strength of the stimulus; (2) location of the stimulus; (3) location of the interneuron. Most identified cells could not readily be assigned to a specific behavior except for the 'T' cell type, which seems intimately involved in most flexion behaviors. The results of this study support the hypothesis that there are few if any 'command neurons', as defined by Kupfermann and Weiss (1978), in the crayfish abdominal positioning system. Abdominal positioning behavior, therefore, is probably under the control of a large network of cells each contributing a small part to the overall motor output.
Abdominal Muscles↗
Percutaneous renal biopsy as a day-patient procedure.
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Ambulatory Care↗
SP-40,40 is an inhibitor of C5b-6-initiated haemolysis.
This study examines the function of SP-40,40, a newly identified component of the SC5b-9 complement complex, in the regulation of the terminal complement pathway. Purified SP-40,40 was shown to inhibit, in a dose-dependent manner, C5b-6-initiated haemolysis. Apparently additive inhibition was also demonstrated in conjunction with complement S-protein, although SP-40,40 appears to be the more potent inhibitor on an equimolar basis. The data suggest that SP-40,40, like S-protein, probably combines with the nascent C5b-7 complex, forming a cytolytically inactive SC5b-7 - SP-40,40 complex. Preparations of S-protein, purified by an established technique, were shown to be contaminated with SP-40,40. Preparations of affinity-purified SP-40,40 were also shown to contain S-protein, suggesting that these proteins may be partially complexed in plasma.
Animals↗
The effect of immunosuppression on vascularised allografts. A preliminary report.
Five vascularised allografts of the knee joint were performed in dogs immunosuppressed with cyclosporin A and azathioprine. Three survived with normal function for 3 to 4 months after operation. One of the unsuccessful grafts had a failed vascular anastomosis, the other an inadequate blood level of cyclosporin A. All three successful grafts healed well. In two, bone scans, radiographs and biopsies were indistinguishable from successful autografts; in the third the blood supply to the graft failed despite patent anastomoses but the graft healed well with good function. All three grafts were rejected within 2 to 3 weeks of withdrawal of cyclosporin A and azathioprine. In non-immunosuppressed dogs, allografts of the knee, both vascularised and non-vascularised, were rejected within a few days of operation. In two non-vascularised allografts, administration of cyclosporin and azathioprine had no apparent effect on the rate of rejection of the graft.
Animals↗
Localization of terminal complement components S-protein and SP-40,40 in renal biopsies.
The terminal complement complex has been implicated in the development of glomerular injury in both experimental and, indirectly, in human glomerulonephritis. Recent data suggests that the terminal complement complex in human glomerulonephritis may be in the cytolytically inactive SC5b-9 form which also contains S-protein and a recently identified protein, SP-40,40. In this study renal biopsies were examined by immunofluorescence to determine the incidence and inter-relation of deposition of the SC5b-9 components C6, C9, S-protein and SP-40,40. All components of SC5b-9 were found in arteries and arterioles, along the tubular basement membrane and in areas of glomerulosclerosis in all biopsies. This deposition was sometimes associated with C3 but never immunoglobulin deposition and correlated with the degree of renal injury. In addition, in biopsies with glomerular deposition of immunoglobulin and C3, the SC5b-9, components co-localized with the immune deposits. Glomeruli without immune deposits or glomerulosclerosis contained none of the SC5b-9 components. The incidence and pattern of distribution of SP-40,40 was similar to that of S-protein, C6 and C9 in all of cases. These data confirm that the terminal complement complex in the kidney is, at least partly, in the SC5b-9 form both in the specific immune glomerular deposition and in the "non-specific" deposition in areas of renal injury. SP-40,40 is also found in the SC5b-9 complex in all forms of renal disease.
Biopsy↗
Absence of competitive interactions among axon terminals of regenerating motor neurons.
Competition among axon terminals is usually considered to contribute to the formation of patterned synaptic connections. During axonal regeneration of motor neurons in the cockroach, leg muscles initially become innervated by appropriate and inappropriate motor neurons. All axon terminals from inappropriate neurons eventually are eliminated, resulting in the reformation of the original innervation pattern. Destruction of an identified motor neuron by the intracellular injection of pronase did not prevent the elimination of inappropriate axon terminals in the muscle normally innervated by that motor neuron. Therefore, competition does not play a role in the reinnervation of the leg muscles. This indicates a major role for specific cell-cell recognition.
Animals↗
SP-40,40, a newly identified normal human serum protein found in the SC5b-9 complex of complement and in the immune deposits in glomerulonephritis.
We report herein the isolation and initial characterization of a novel protein, termed SP-40,40, which is present at moderate levels (35-105 micrograms/ml) in normal human serum. SP-40,40 is deposited in the renal glomeruli of patients with glomerulonephritis but is not found in normal glomeruli. The protein is a heterodimeric structure of relative molecular mass 80 kD, both chains of which are of a similar size (40 kD). The amino-terminal sequences of both chains are unrelated to one another and possess no significant homology to any known protein sequence. The tissue distribution of SP-40,40 closely resembles that of the terminal complement components and its physicochemical properties are similar to, but distinct from, those of the S protein of complement. We have identified SP-40,40 in the SC5b-9 complex of complement and have demonstrated incorporation of labeled SP-40,40 into this complex. These data suggest that SP-40,40 is an additional component of SC5b-9.
Amino Acid Sequence↗
Identification of the components of glomerular immune deposits using monoclonal antibodies.
Monoclonal antibodies have been raised against components of glomerular immune deposits in experimental glomerulonephritis and idiopathic human glomerulonephritis. An accelerated model of chronic serum sickness in the rat using cationized human serum albumin was employed to obtain renal tissue with capillary loop and mesangial immune deposits. Mice were immunized with isolated rat glomeruli or a preparation of glomerular basement membrane and mouse spleen cells fused with myeloma cells. Anti-human serum albumin monoclonal antibodies were produced from all technically successful fusions irrespective of the size of the deposits in the immunizing tissue or whether whole glomeruli or glomerular basement membrane were used for immunization. Monoclonal antibodies were then produced following immunization with tissue from postmortem human kidneys with idiopathic membranous and mesangiocapillary glomerulonephritis. Sixteen monoclonal antibodies, apparently reactive with glomerular immune deposits, were cloned; most of these were reactive with components of the complement system including a previously undescribed complement-related protein. These studies demonstrate that monoclonal antibody technology may be useful in determining the identity of antigen and non-antigen components of glomerular immune deposits.
Animals↗
Idiopathic membranous glomerulonephritis: long-term follow-up in 139 cases.
The clinical course of 139 patients (77 male, 62 female) with idiopathic membranous glomerulonephritis is reviewed. The median duration of follow-up was 52 months; 45% and 25% were followed for more than 5 and 10 years respectively. The median age at presentation was 36. Fifty-four percent of patients had the nephrotic syndrome at presentation. Half of the patients were treated at some stage with cyclophosphamide or corticosteroids. During the course of follow-up some deterioration in renal function occurred in only 20% of patients. The patients who suffered deterioration in renal function were mainly male and had significantly worse renal function and a higher incidence of the nephrotic syndrome than the other patients at presentation. Only 7 male patients (5%) developed terminal renal failure during follow-up and one female presented in terminal renal failure. Survival was 88% and 81% at 5 and 10 years. The median predicted (or actual) time for development of terminal renal failure in patients with progressive deterioration was 7.3 years. These data are in accord with other recently published series which have described a relatively benign prognosis for idiopathic membranous glomerulonephritis.
Adolescent↗
Comparison of the prophylactic effects of 2-deoxycytidine and prednisolone for high-dose intravenous cytarabine-induced keratitis.
In a double-masked, randomized fashion, 11 patients with hematologic malignancies received 13 courses of high-dose cytarabine therapy, intravenously (3 g/m2 every 12 hours for five to six days). Each patient received topical prednisolone phosphate 1% in one eye and 2-deoxycytidine 100 microM in the other eye every six hours. Topical therapy was initiated 12 hours before the first cytarabine dose and continued for up to ten days (until four to five days after completion of cytarabine therapy). Slit-lamp biomicroscopy was performed before therapy and then weekly for one month. 2-Deoxycytidine was equally as effective as the topical corticosteroid therapy in reducing photophobia and pain, microcysts, and punctate epithelial erosions, and each treatment gave results significantly better when compared historically to placebo-treated eyes.
Administration, Topical↗
Serum sickness nephropathy in the rat using cationized albumin: effect of preimmunization and antigen dose.
A model of glomerulonephritis induced in preimmunized rats with cationic albumin is described. Extensive glomerular immune complex formation and a severe nephrotic syndrome occurred within 5 days of commencement of daily intravenous injections. Severity of disease was markedly influenced by the degree of preimmunization and, to a lesser extent, by the dose of cationic albumin administered. Immune deposits, although initially confined along the capillary loops, were seen at all sites in the glomerulus. This study confirms that, in rats, the use of cationic antigens accelerates the development of 'serum sickness' nephropathy but preimmunization is necessary to produce significant disease.
Animals↗
Chronic Propionibacterium endophthalmitis after extracapsular cataract extraction and intraocular lens implantation.
We studied six cases of chronic, indolent intraocular inflammation that occurred after extracapsular cataract extraction and posterior chamber intraocular lens implantation. The inflammation was characterized by a delayed onset, and in three cases had the clinical appearance of a granulomatous iridocyclitis. Cultures of intraocular specimens obtained from six eyes yielded Propionibacterium; five yielded P. acnes. Pleomorphic gram-positive bacilli consistent with Propionibacterium were identified in cytologic or histopathologic studies in four of the six culture-positive cases. After surgical and medical therapy, the inflammation resolved. Postoperative Propionibacterium endophthalmitis may masquerade as a chronic iridocyclitis.
Aged↗
Membranous glomerulonephritis and Landry-Guillain-Barre syndrome.
Two cases of idiopathic membranous glomerulonephritis associated with acute inflammatory demyelinating polyradiculoneuropathy (Landry-Guillian-Barre syndrome) are described. In both of the patients, the onset of the nephrotic syndrome coincided with the development of severe ascending sensorimotor neuropathy. Although this association has previously been reported in four other isolated cases, it is not generally recognized by nephrologists and may be of significance in the future understanding of the immunopathogenesis of both diseases.
Aged↗
Renovascular hypertension: treatment with the oral angiotensin-converting enzyme inhibitor enalapril.
Sixteen patients with an established diagnosis of renovascular hypertension were entered in an open study of enalapril (MK421), an oral angiotensin-converting enzyme (ACE) inhibitor, for treatment of their hypertension. Initial blood pressure was 178.9 +/- 6.3/106.2 +/- 3.1 mm Hg during conventional therapy on a median of 3 different antihypertensive agents. All antihypertensive therapy was ceased and the patients admitted to hospital. Following introduction of enalapril, blood pressure fell to 161.5 +/- 6.9/90.6 +/- 4.1 mm Hg at 24 h (p less than 0.01 systolic and diastolic). Blood pressure control (diastolic blood pressure, phase V, less than 95 mm Hg) was achieved with monotherapy in 7 patients and in a further 5 patients with addition of a diuretic. Renal function was compromised in 4 patients, requiring cessation of enalapril in 2 instances. Enalapril is an oral ACE inhibitor useful in the treatment of renovascular hypertension. Close monitoring of renal function is necessary during the introduction of enalapril therapy in patients with renovascular hypertension.
Adult↗