Features of chronic asthma include airway hyperresponsiveness, inflammatory infiltrates, and structural changes in the airways, termed remodeling. The contribution of eosinophils, cells associated with asthma and allergy, remains to be established. We show that in mice with a total ablation of the eosinophil lineage, increases in airway hyperresponsiveness and mucus secretion were similar to those observed in wild-type mice, but eosinophil-deficient mice were significantly protected from peribronchiolar collagen deposition and increases in airway smooth muscle. These data suggest that eosinophils contribute substantially to airway remodeling but are not obligatory for allergen-induced lung dysfunction, and support an important role for eosinophil-targeted therapies in chronic asthma.

https://science.sciencemag.org/content/sci/305/5691/1776.full.pdf

A critical role for eosinophils in allergic airways remodeling

Two hundred and seventeen patients presenting with abdominal aneurysms in the Department of Surgery at the Manchester Royal Infirmary between the years 1958–69 were surveyed retrospectively.



One hundred and eighty-seven of the patients underwent operation for resection of their aneurysms; of these, 19 (10 per cent) showed excessive thickening of the aneurysm walls and perianeurysmal adhesions at operation.



Subsequent histological examination of the walls of these unusual aaneurysms showed extensive active chronic inflammatory changes, including plasma-cell infiltration.



This group of patients whose aneurysms we describe as ‘inflammatory’ presented with different clinical features in comparison with the atherosclerotic group.



Retrospective investigation has not yet revealed any aetiological factors. We feel that ‘inflammatory’ aneurysms are a discrete entity with significant differences from atherosclerotic aneurysms and previously described arteritis.

Inflammatory aneurysms of the abdominal aorta.

Hypertension due to a renin-secreting renal tumour

Septic shock is one of the leading causes of acute kidney injury. The mechanisms of this injury remain mostly unknown notably because of the lack of data on renal histological lesions in humans. Kidney biopsy was performed immediately post-mortem in consecutive patients who died of septic shock. Comparisons were made with specimens from eight patients who died of trauma on scene and nine ICU patients that died of non-septic causes. Nineteen septic patients were included, 11 were male, and age was 72 ± 12 years. Anuria occurred in all patients 2.2 ± 1.4 days before death. Seven patients had disseminated intravascular coagulation. In all patients we observed (1) acute tubular lesions whose intensity correlated with blood lactate concentration; (2) intense infiltration by leukocytes, mainly monocytic, in glomeruli and interstitial capillaries as compared to controls; (3) presence of tubular cell apoptosis proved by the presence of apoptotic bodies (2.9% of tubular cells) significantly more frequently than in controls and confirmed by TUNEL and activated caspase-3 staining. Arteriolar/arterial thromboses were observed in only 4 of 19 patients, without any association with presence of disseminated intravascular coagulation. Kidney lesions in septic shock go beyond those associated with simple acute tubular injury, notably capillary leukocytic infiltration and apoptosis. Vascular thrombosis, however, did not appear to play a major role in the majority of patients. The extent to which these lesions are specific to sepsis or are common to all multi-organ failure independent of its cause is yet to be elucidated.

/pdf/histopathology-of-septic-shock-induced-acute-kidney-injury-1neeu6bcw5.pdf

Histopathology of septic shock induced acute kidney injury: apoptosis and leukocytic infiltration

Angiogenesis is essential for normal mammalian development and is controlled by the local balance of pro- and antiangiogenic factors. Here we describe a novel mouse cDNA sequence encoding sFLT-1 that is a potent antagonist to vascular endothelial growth factor (VEGF) and show for the first time its in vivo production. In situ hybridization and Northern blot analysis with probes specific for sFLT-1 or FLT-1 showed that the relative abundance of their mRNAs changed markedly in spongiotrophoblast cells in the placenta as gestation progressed. On day 11 of pregnancy, sFLT-1 mRNA was undetectable but FLT-1 readily apparent, and by day 17 sFLT-1 mRNA was abundant but FLT-1 barely detectable. sFLT-1 was identified in conditioned medium of cultured placenta from day 17 pregnant mice and likely to be present in the circulation, as there is a substantial increase of VEGF-binding activity in the serum from day 13 of pregnancy, which coincides with the abundant sFLT-1 expression in placenta. Expression of sFLT-1 was also observed in adult lung, kidney, liver, and uterus. These data suggest a novel mechanism of regulation of angiogenesis by alternative splicing of FLT-1 pre-mRNA. Treatment of pregnant mice with exogenous VEGF from day 9 to 17 of pregnancy, which alters the ratio of VEGF to sFLT-1, resulted in an increase in the number of resorption sites and fibrin deposition in the placenta of ongoing pregnancies. These findings have important implications for understanding placental function and may be relevant in a range of disease states.

/pdf/alternative-splicing-of-vascular-endothelial-growth-factor-2ao0q0dnzh.pdf

Alternative splicing of vascular endothelial growth factor (VEGF)-R1 (FLT-1) pre-mRNA is important for the regulation of VEGF activity.

There are few satisfactory staining methods for fibrin. There are even fewer clear definitions of the material for which these methods are commended. In sections of tissue the older pathologists recognized three phenomena to which they gave the name fibrin. These were: (a) The networks and more solid masses within blood vessels that formed a large part of the substance of what had been seen with the naked eye as a thrombus; (b) the extravascular networks ofsomewhat comparable structure associated with acute inflammation and seen in the interstitial tissue, in the arachnoid space, or in pneumonic alveoli; and (c) the more solid and plaque-like masses occurring on serous surfaces. When observations came to be made on the hyaline eosinophilic fibrin-like material found to be present in pathological processes other than simple coagulation and the pyogenic lesions, the names given to it were curiously varied. It is a measure of this vagueness that in tissues from rheumatic disease of the heart the eosinophilic deposit on the epicardial surface was called 'fibrin', a comparable deposit in the superficial layers of the mitral valve was called 'platelets', and the eosinophilic and slightly refractile network of the reticular Aschoff body was called 'fibrinoid'. Within recent years, almost contemporaneously with the falling incidence of acute pyogenic inflammation, there has been an increasing recognition and experience of this fibrin-like material which, with the classical methods for staining fibrin, gives varied degrees of positiveness; typical examples are the intra-alveolar networks in the lungs of subjects with uraemia or cardiac failure, and the deposits of hyaline materials within the walls of blood vessels ('fibrinous vasculosis', Lendrum, 1955, 1956) as seen in systemic and pulmonary hypertension, in areas of infarction, and in the diseases which for want of more exact knowledge we group under the term 'sensitization'. It is fashionable still to call this material 'fibrinoid' but the new methods for demonstrating fibrin described below all give a sharp, contrasty snining reaction with this material, a finding which encourages us to abjure this melodious but misleading term. The fact of identical staining reaction on these

https://jcp.bmj.com/content/jclinpath/15/5/401.full.pdf

Studies on the character and staining of fibrin

This describes the sodium sulphate-Alcian Blue (SAB) method for staining amyloid in paraffin sections. Its value lies in the possibility of subsequent counterstaining and thus of revealing the structural relationships of amyloid. In the kidney the topical disposition of amyloid closely resembles the disposition of fibrin in the kidney of diabetics; this suggests that upset in vascular permeability plays a part in determining the site of the amyloid deposits. Furthermore, an aging process in amyloid can now be envisaged resembling the aging of extraluminal fibrin. Both materials proceed to a hyalin material that, staining like collagen, merits the name pseudo-collagen. This term we apply to a hyalin, staining like collagen, for which, we can postulate a specific precursor.

https://jcp.bmj.com/content/jclinpath/25/5/373.full.pdf

A. C. Lendrum

Papers

Studies on the character and staining of fibrin

Renal hyalin. A study of amyloidosis and diabetic fibrinous vasculosis with new staining methods.