Christmas candy maker's asthma. IgG4-mediated pectin allergy

We evaluated a 29-year-old candy maker with no history of asthma who developed asthma after exposure to pectin, a compound manufactured from fruits and fruit rinds. Following eight years of employment during which he added pectin to a recipe for Christmas candies, the candymaker developed acute respiratory symptoms. Challenge testing with the pectin mixture caused a 40 percent decrease in FEV1. Skin prick testing was positive to the pectin extract. Total IgE was normal and pectin-specific IgE antibodies were not detected. A strongly positive pectin-specific IgG4 antibody response was present that was not detected in a control serum and could be inhibited by the addition of pectin. Antigen-specific IgG4 should be sought in IgE negative cases of occupational asthma.     

Elevated lipoprotein (a) levels in primary nephrotic syndrome

Elevated plasma levels of total cholesterol and increase in the hepatic synthesis of some apo B-containing lipoproteins have been noted in the nephrotic syndrome. Apoprotein (a), the apolipoprotein distinguishing lipoprotein (a) [Lp(a)] from low-density lipoprotein, is equally of hepatic origin, and Lp(a) recently has been shown to possess both atherogenic and thrombogenic activities. However, little is known of Lp(a) levels in nephrotic patients. We measured plasma Lp(a) concentrations in 11 patients with primary nephrotic syndrome in the absence of hematuria, hypertension, and renal insufficiency. Histologic lesions were minimal-change disease in five cases, membranous glomerulopathy in four cases, and focal and segmental glomerulosclerosis in two cases. Mean levels of Lp(a) (98 +/- 92 mg/dL [mean +/- SD]) were markedly elevated in the nephrotic patients as compared with the controls (14 +/- 13 mg/dL). No correlation was noted between plasma Lp(a) and proteinuria, albuminemia, total cholesterolemia, low-density lipoprotein cholesterol, apoprotein B100, or plasminogen. Furthermore, there was no correlation between Lp(a) levels and apoprotein (a) isoform size. In four patients, the level of Lp(a) decreased approximately fourfold after remission of the nephrotic syndrome under corticosteroid treatment. Our observation that Lp(a) levels are elevated in the nephrotic syndrome is consistent with the hypothesis that these patients may be at an increased risk of cardiovascular and thrombotic complications.     

Experimental cyathostome challenge of ponies maintained with or without benefit of daily pyrantel tartrate feed additive: comparison of parasite burdens, immunity and colonic pathology

Eighteen mixed-breed, naturally infected ponies ranging in age from 1 to 16 yr and four cyathostome-na?ve ponies reared and maintained under parasite-free conditions ranging in age from 1 to 4 yr were used in this study. Naturally-infected ponies were treated with 1 dose of ivermectin (IVM) at 200 micrograms kg-1, followed by a 5-day regimen of oxibendazole (OBZ) at 20 mg kg-1 to remove existing cyathostome burdens; cyathostome-na?ve control ponies were treated with IVM alone. The naturally infected ponies were matched on age and gender, then randomly assigned to one of three treatment groups of six animals per group; the four cyathostome-na?ve ponies constituted a fourth group. Following OBZ treatment, Group 1 ponies were treated with pyrantel tartrate (PT) in their pelleted ration; the remaining ponies received only the pelleted ration. Beginning on experiment Day 3, a daily challenge infection of 10(4) mixed cyathostome larvae was administered orally to ponies of Group 1, Group 2 and the cyathostome-na?ve controls. Group 3 ponies served as unchallenged controls to determine residual parasite burdens following IVM/OBZ treatment. Necropsy examinations were performed on three Group 3 ponies on Day 1; the remainder of the necropsy examinations began on Day 41. Cyathostome burdens were evaluated by recovery of larvae and adults from the luminal contents, by digestions of the intestinal mucosa, and by mural transillumination of full-thickness intestinal sections. Differences in postchallenge clinical responses were also compared. Necropsy examinations included comparisons of grossly visible inflammation of the large bowel, weights of biopsy specimens from each region, and histologic evaluations of these biopsies. Parasite recoveries at necropsy indicated a strong protective effect derived from daily PT treatment. Mean weights of intestinal biopsies corresponded with worm burdens, but histological evaluation did not reveal architectural or cellular changes to account for the increase in weight; therefore, edema was suspected. A strong age-related resistance to challenge infection was apparent in both the PT-treated and control groups by virtue of the lower mean worm burdens found in older ponies compared to younger ponies of the same treatment group; however, daily PT treatment of older ponies reduced the variability of their worm burdens to a uniformly low level. Comparisons of luminal and mucosal parasite burdens of age stratified nontreated controls further suggest that the age related resistance, which is acquired, targets increasing numbers of parasite stages as this resistance matures. Further, there is no evidence for an immune mediated acquisition of hypobiotic L3.     

An induction machine model for predicting inverter-machineinteraction

The conventional qd induction motor model typically used in drive simulations is very inaccurate in predicting machine performance, except perhaps for the fundamental component of the current and the average torque near rated operating conditions. Predictions of current and torque ripple are often in error by a factor of two to five. This work sets forth an induction machine model specifically designed for use with inverter models to study machine-inverter interaction. Key features include stator and rotor leakage saturation as a function of current and magnetizing flux, distributed effects in the rotor circuits, and a highly computationally efficient implementation. The model is considerably more accurate than the traditional qd model, particularly in its ability to predict switching frequency phenomena. The predictions of the proposed model are compared with those of the standard qd model and to experimental measurements on a 37 W induction motor drive     

Changes in field potentials and membrane currents in rat sensorimotor cortex following repeated tetanization of the corpus callosum in vivo

Repeated, daily tetanization of the corpus callosum induces lasting changes in sensorimotor cortex field potential responses, but the synaptic populations that mediate these responses and support long-term potentiation (LTP) have not been characterized. Current source density analyses of field responses were compared between control animals and those in which LTP was induced by 10 daily series of tetanizations. Tetanization and paired-pulse stimulation (100 ms interval) enhanced the duration of initial (approximately 3 ms onset) deep-negative population spike activity generated by a current sink in layer V that peaked repeatedly at a frequency of approximately 400 Hz. The early (approximately 10 ms to peak) surface-negative component of field responses was generated by a current sink in upper layer V and a source in layer VI. This monosynaptic component followed high stimulation frequencies, recovered quickly from the effects of anaesthesia, and was enhanced by both tetanization and paired-pulse stimulation. The late (approximately 20 ms to peak) surface-negative component was generated by a sink in upper layer V and a source deep in layer V, and was greatly enhanced by tetanization and paired-pulse stimulation. The late component did not follow high-frequency stimulation and recovered slowly from anaesthesia, suggesting that it is driven polysynaptically. Potentiation of monosynaptic thalamic and cortico-cortical afferents probably mediates enhancements of the early component and population spikes, while potentiation of polysynaptic afferents to layer V may contribute to growth in the late component.     

CD11b+CD28-CD4+ human T cells: activation requirements and association with HLA-DR alleles

Engagement of CD28 induces a major costimulatory pathway required by many CD4+ T cells in addition to activation via the TCR. In the absence of signals provided by CD28, ligation of the TCR alone can induce anergy or apoptosis in CD28+ cells. However, we report here characterization of a distinct subset of CD4+ T cells that are CD28-. Three autoreactive CD4+ human T cell clones that could be activated to produce IL-2 and proliferate by anti-CD3 alone were found to lack expression of CD28. CD28- clones that were activated with anti-CD3 alone were not anergic to restimulation via CD3. The presence of CD28-CD4+ T cells was verified in peripheral blood, and their frequency ranged from 0% to >22% of CD4+ T cells in different individuals. The percentage of CD28-CD4+ T cells in the peripheral blood of 57 individuals was significantly correlated with specific class II MHC alleles. Persons with HLA-DRB1*0401 and DR1 alleles had significantly higher numbers of CD28- T cells, while individuals with HLA-DR2(15) had significantly fewer CD28-CD4+ T cells than the mean. Like the CD28- clones, CD28-CD4+ T cells isolated from peripheral blood proliferated upon CD3 cross-linking in the absence of costimulation. The finding that CD28-CD4+ T cells resist induction of anergy following engagement of the TCR in the absence of conventional costimulation demonstrates one mechanism by which autoreactive T cells can escape processes that censor self-reactivity. The MHC associations observed suggest a relationship with autoimmunity and loss of self-tolerance.     

Phase I/II trial of combined 131I anti-CEA monoclonal antibody and hyperthermia in patients with advanced colorectal adenocarcinoma

BACKGROUND: This pilot project was undertaken to evaluate the toxicity of and tumor response to combined 131I anti-carcinoembryonic antigen monoclonal antibody (131I anti-CEA RMoAb) and hyperthermia in patients with metastatic colorectal adenocarcinoma. METHODS: Nine patients who had colorectal carcinoma with liver metastases were enrolled in this study. Intact 131I anti-CEA RMoAb was used (the specific antibody was IMMU-4, provided by Immunomedics, Inc., Morris Plains, NJ). During the diagnostic phase, dosimetry revealed that the tumor site received a higher radiation dose than the surrounding normal tissues in only six patients. These six, who were treated with radioimmunotherapy and hyperthermia, were the basis of this study. The first three patients were treated with 30 mCi/m2 of 131I anti-CEA RMoAb, and the next three received 60 mCi/m2. Pharmacokinetic clearance data were reported for all nine patients. RESULTS: Thermometry data revealed an average T90 of 40.3 (+/- 1.4 degrees C) and T50 of 41.1 (+/- 1.2 degrees C). The average thermal dose equivalent at 42.5 degrees C was 34.5 (+/- 21.5) minutes. The average Tmin, Tmax, and Tmeam were 40 (+/- 1.2 degrees C), 42.4 (+/- 0.7 degrees C), and 41.1 (+/- 1.1 degrees C), respectively. The pharmacokinetic clearance data of antibody showed monoexponential plasma clearances in all patients except one, in whom a biexponential plasma clearance was observed. In general, similar plasma and whole-body clearances as well as similar urinary excretions were observed when diagnostic and therapeutic phases for each patient were compared. Two of the six patients showed a marked improvement in their symptoms; five patients showed a drop in carcinoembryonic antigen levels. A follow-up computed tomography scan one month after treatment showed no change in tumor volume in five patients; one patient showed a partial response. Three patients developed toxicity, two developed moderate thrombocytopenia (39,000 and 58,000), and the other patient developed hematoma resulting from the insertion of a catheter for thermometry. CONCLUSIONS: It is feasible to combine hyperthermia and radiolabeled monoclonal antibodies, and the combination was well tolerated by these patients. The interaction between hyperthermia and low dose rate radioimmunotherapy is complex. Further studies are necessary to explore the use of this combined modality in the management of maligancies.