Cross-reactivity to eel, eelpout and ocean pout in codfish-allergic patients

Fish allergy is one of the most common food allergies in both children and adults and patients with allergic reactions to one fish species have in many cases been given the advice to avoid all fish, without further evaluation. The possible common reactivity between different fish species is not well studied. Because of this and a possible exploitation of fish species hitherto not much used in the Scandinavian diet ocean pout, eelpout and eel were evaluated. We examined the serological and biological cross-reactivity of these species in double-blind challenged-confirmed codfish-allergic patients using CAP, Maxisorp-radio allergosorbent test (RAST) inhibition, western blot, skin prick test (SPT) and histamine release (HR). All 18 codfish allergic patients had specific IgE to ocean pout, eelpout and eel determined by Maxisorp-RAST. All four fish species could induce basophil HR using blood from 16 of 18 patients and all patients tested reacted in SPT. This study demonstrates that patients with a verified clinical allergy to codfish in a high frequency express biological cross-reactivity to other fish species. By RAST inhibition this common reactivity was shown to be a true cross-reactivity.     

Caspase-cleavage of tau is an early event in Alzheimer disease tangle pathology

Neurofibrillary tangles (NFTs) are composed of abnormal aggregates of the cytoskeletal protein tau. Together with amyloid beta (Abeta) plaques and neuronal and synaptic loss, NFTs constitute the primary pathological hallmarks of Alzheimer disease (AD). Recent evidence also suggests that caspases are activated early in the progression of AD and may play a role in neuronal loss and NFT pathology. Here we demonstrate that tau is cleaved at D421 (DeltaTau) by executioner caspases. Following caspase-cleavage, DeltaTau facilitates nucleation-dependent filament formation and readily adopts a conformational change recognized by the early pathological tau marker MC1. DeltaTau can be phosphorylated by glycogen synthase kinase-3beta and subsequently recognized by the NFT antibody PHF-1. In transgenic mice and AD brains, DeltaTau associates with both early and late markers of NFTs and is correlated with cognitive decline. Additionally, DeltaTau colocalizes with Abeta(1-42) and is induced by Abeta(1-42) in vitro. Collectively, our data imply that Abeta accumulation triggers caspase activation, leading to caspase-cleavage of tau, and that this is an early event that may precede hyperphosphorylation in the evolution of AD tangle pathology. These results suggest that therapeutics aimed at inhibiting tau caspase-cleavage may prove beneficial not only in preventing NFT formation, but also in slowing cognitive decline.     

Molecular dating of senile plaques in the brains of individuals with Down syndrome and in aged dogs

beta-Amyloid (Abeta) is a constituent of senile plaques found with increasing age in individuals with Down syndrome (DS) and in the canine model of aging. Sections of DS and dog brain were immunostained using an affinity-purified polyclonal antibody for a posttranslationally modified Abeta with a racemized aspartate at position 7 (d7C16). The immunostaining characteristics of d7C16 Abeta in DS and dog brain indicate that it is present in all plaque subtypes, including the thioflavin-S-negative diffuse plaques that develop with age in dogs. The youngest DS case exhibited weak immunolabeling for d7C16 but the extent of d7C16-positive plaques increased with age. In addition, d7C16-positive plaques were initially found in clusters in the superficial layers of the frontal and entorhinal cortex but, with advancing age, increasing numbers appeared in deeper layers, suggesting a progression of Abeta deposition from superficial to deeper cortical layers. Ultrastructural studies in DS brain were confirmed using perfused dog brain and provided consistent results; thioflavin-S-negative diffuse plaques consist of fibrillar Abeta and racemized Abeta is associated with thicker and more highly interwoven fibrils than nonracemized Abeta. The use of antibodies to modified forms of the Abeta protein should provide insight into the progression of plaque pathology in DS and Alzheimer's disease brain.     

Immunohistochemical detection of epidermal growth factor receptor in human high-grade astrocytomas--a comparison between frozen- and paraffin sections

The overexpression of epidermal growth factor receptor (EGFR) in human astrocytic tumours is associated with the oncogenesis of these tumours. Ongoing research on diagnostic, prognostic, and therapeutic aspects of this receptor is highly dependent on the development of reliable techniques for the detection of EGFR in tumour tissue. The aim of this study was to assess EGFR expression in human high-grade astrocytomas by means of immunohistochemistry on formalin-fixed, paraffin-embedded sections and to compare these findings with the results of our previous study on frozen sections from these tumours, in which we found about 60% EGFR positivity (10). Four anaplastic astrocytomas and 19 glioblastomas were included in this study. Two different antibodies were used, the monoclonal antibody E30 reactive against the extracellular domain of EGFR and the polyclonal antibody Ab-4 directed against its cytoplasmic domain. With E30, 3 out of 4 anaplastic astrocytomas (75%) and 12 out of 19 glioblastomas (63%) were found to express EGFR whereas Ab-4 demonstrated positive EGFR immunoreactivity in most of the tumours (18/19 glioblastomas and all the 4 anaplastic astrocytomas). In conclusion, immunohistochemistry represents a reliable and convenient technique for the detection of EGFR in tissue sections of human high-grade astrocytomas, and that EGFR immunoreactivity is comparable in frozen- and paraffin sections from these tumours.     

Seasonal changes in spermatogenic activity and in plasma levels of FSH, LH and testosterone, and the effect of immunization against inhibin in the male silver fox (Vulpes vulpes)

The cellular composition of the silver fox testis assessed by DNA flow cytometry and histological analysis exhibited marked circannual alterations. The proportion of haploid cells increased from late October to the breeding season in February, while that of diploid cells decreased and that of tetraploid cells fluctuated during the same period. Towards the end of March these changes were reversed. The seasonal variations in testicular histology paralleled the changes in distribution of cells from the different DNA populations. In August, 69% of the tubules contained spermatogonia as the only type of germ cell, while the remaining 31% also contained a few primary spermatocytes. In late October more than 50% of the tubules contained spermatocytes, and during the period of further activation from early December-February the seminiferous epithelium included round and/or elongated spermatids as well. In February, all tubules contained complete associations of germ cells, whereas in late March tubules with spermatogonia only and spermatogonia together with a few spermatocytes reappeared. In May, only such tubules could be found indicating total regression. Plasma concentrations of FSH and LH increased from early November, both gonadotrophins reaching maximum levels in December or early January, and then both declined during the second part of January, immediately prior to the actual breeding season. LH values showed a few smaller peaks in the beginning of June, whereas FSH levels were generally low until the next period of testicular reactivation. Testosterone concentrations were also low during most of the year but rose in November and December to reach a peak in January and a second peak in June. In animals immunized against inhibin the distribution of haploid, diploid and tetraploid cells did not deviate to any great extent from that in the controls, except in March when the immunized males had a markedly lower proportion of tetraploid cells, and in May, when they had a distinctly higher proportion of haploid cells. These findings were partly reflected by the histology. In the immunized animals, plasma FSH levels started to increase at approximately the same time but peaked higher and remained elevated almost 1 month longer than in the controls, whereas both the rise and decline in LH levels generally coincided with the variations in these animals, but the values were mostly higher. The testosterone profiles were similar to those in the controls except that the maximum values were also usually higher.     

Comparison of Three Triple Regimens with Omeprazole or Ranitidine Bismuth Citrate for Helicobacter pylori Eradication

Background: Regimens with ranitidine bismuth citrate (RBC) or omeprazole (O) are effective in eradicating Helicobacter pylori. This randomized, open, multicentre trial compares three different regimens with these drugs. Methods: Consecutive H. pylori +ve outpatients were included. The alternative regimens were: 1) O 20 mg, clarithromycin (C) 250 mg and metronidazole (M) 500 mg (O·3;C·3;M), 2) RBC 400 mg, C 250 mg and M 500 mg (RBC·3;C·3;M), 3) RBC 400 mg, tetracycline (T) 1000 mg and M 500 mg [RBC·3;T·3;M]. All drugs were given twice daily for 7 days. H. pylori infection was assessed with H. pylori urea breath tests. Results: 426 H. pylori +ve patients were included (mean age 58 years [range 18-88], male/female: 244/182). The eradication rates (intention to treat) in the O·3;C·3;M, RBC·3;C·3;M and RBC·3;T·3;M groups were 117/137 (85%), 141/146 (97%) and 117/143 (82%), respectively ( P < 0.001, overall assessment). There were no significant differences in side effects between the alternatives. Conclusion: In this trial, RBC·3;C·3;M was the most effective one, it was well tolerated and compliance was satisfactory. RBC·3;T·3;M is an alternative to regimens with clarithromycin.     

Patients with Functional Dyspepsia Responding to Omeprazole Have a Characteristic Gastro-oesophageal Reflux Pattern

Background: The effect of acid secretion inhibitors in patients with functional dyspepsia (FD) is equivocal. One previous trial showed an effect in patients with a characteristic gastro-oesophageal reflux pattern. This double-blind trial compares the number of reflux episodes in responders and non-responders to omeprazole. Methods: Twenty-four patients (men/women, 11:13; mean age, 49 years) with FD were included; those with reflux as the main symptom were excluded. An upper endoscopy and a 24-h oesophageal pH measurement were performed before randomization to treatment with 10-20 mg omeprazole or placebo for 4 weeks. Patients who at questioning considered themselves to have achieved sufficient relief of dyspeptic symptoms after 4 weeks were characterized as responders. Results: The number of responders in the omeprazole and placebo groups was 8 of 14 (57%) and 2 of 10 (20%), respectively (P = 0.07). The mean number of reflux episodes at the 24-h oesophageal pH measurement in responders and non-responders to omeprazole was 57 and 25, respectively (P     

Spontaneous enterochromaffin-like cell carcinomas in cotton rats (Sigmodon hispidus) are prevented by a somatostatin analogue

Among inbred female cotton rats (Sigmodon hispidus) 25-50% of the animals develop spontaneous gastric carcinomas; the corresponding figure for male cotton rats is approximately 1%. Animals with carcinomas have hypergastrinaemia and gastric hypo-anacidity and the tumours are derived from enterochromaffin-like (ECL) cells. The mechanism behind the hypo-anacidity is unknown. Carcinomas are found in all female cotton rats with hypergastrinaemia lasting more than 4 months and this represents an excellent animal model for studying gastric carcinogenesis. In this study, the somatostatin analogue octreotide was given to female cotton rats to prevent carcinoma development caused by hypergastrinaemia. Twelve female cotton rats were given monthly injections of long-acting octreotide (5 mg i.m.) for 6 months. A control group of 20 animals was not given injections. Of the 20 control animals, 13 developed hypergastrinaemia and histologically invasive carcinomas or dysplasia. Of the 12 animals in the octreotide group, five developed hypergastrinaemia. None of these five animals developed histological cancer (P<0.05), whereas three had dysplasia. However, octreotide did not affect plasma gastrin concentration or antral gastrin mRNA abundance significantly. Dysplasia of the oxyntic mucosa in hypergastrinaemic animals was accompanied by a marked increase in chromogranin A-immunoreactive cells and cells positive for Sevier-Munger staining. The malignant tissue also contained groups of cells with Sevier-Munger staining. In conclusion, octreotide prevented ECL cell carcinomas in hypergastrinaemic cotton rats without lowering the gastrin concentration.