Pathogenesis of neuroimmunologic diseases. Experimental models

Development of the retina, like that of other tissues, occurs via an orderly sequence of cell division and differentiation, producing the functional retina. In teleost fish, however, cell division and differentiation in the retina continue throughout the life of the animal in two distinct ways. Stem cells in a circumferential germinal zone at the periphery of the retina give rise to all retinal cell types and progenitor cells located throughout the retina in the outer nuclear layer (ONL) produce new rod photoreceptors. These processes in adult retina recapitulate in space the embryonic events responsible for forming the retina. Analysis of these events in an African cichlid fish, Haplochromis burtoni, confirmed that cone photoreceptors differentiate first, followed by rod photoreceptors. Correspondingly, at the margin of the eye, cone photoreceptors differentiate nearer to the margin than do rods. Control of photoreceptor production is not understood. Here we present the time of appearance and distribution pattern of GABA and vimentin which are candidates for the control of retinal cell division and differentiation. Antibody staining reveals that both GABA and vimentin exhibit unique patterns of expression during embryonic retinal development. Vimentin immunoreactivity is evident throughout the retina in a spoke-like pattern between developmental Days 4 and 7, as both cone and rod photoreceptors are being formed. GABA is expressed in horizontal cells between Days 5 and 7, corresponding to the onset of rod differentiation in time and in position within the retina. Moreover, the wave of GABAergic staining in the horizontal cells parallels the wave of rod differentiation across the embryonic retina of H. burtoni. Thus, GABA may play a role in the development of rod photoreceptors.     

Broiler industry strategies for control of respiratory and enteric diseases

The commercial broiler industry is a modern day agricultural success due to popular consumer demand, healthy flocks, and least cost production. Preventive medicine is the key for economical control of disease in integrated broiler companies, and includes quarantine-eradication, controlled-exposure, and preventive feed medication. Respiratory and enteric diseases present a continuing, potential threat for economic loss. Most exotic and egg-transmitted poultry diseases have been controlled by reduction or eradication policies. Endemic diseases are controlled by mass vaccination and preventive feed medication. Improvements in genetics, housing, equipment, and disease surveillance has allowed continued improvements in disease prevention. Attention to detail and management of risk is crucial to industry success. With fast industry growth and market maturity of the broiler industry, new challenges have risen. These challenges include increased poultry house density, increasing economic pressures, changing industry attitudes, and increased governmental regulations that will strain the continued success of today's control strategies.     

Hypertension in diseases of the kidney. Pathogenesis and therapy

Renal disease is the cause of hypertension in about 5% of all hypertonics. Patients with renal hypertension are threatened by cardiovascular complications of hypertension even more frequently than patients with essential hypertension. Hypertension is moreover an important factor in the progression of renal insufficiency. In the pathogenesis of renal hypertension an important role is played by sodium and fluid retention and activation of the renin-angiotensin system. Progression of rental insufficiency can be retarded only by more strict control of hypertension than in patients with normal renal function. Optimal treatment is administration of angiotensin converting enzyme inhibitor which moreover in the majority of patients retards the progression of renal insufficiency more markedly than other antihypertensive drugs.     

Pathogenesis of dengue virus diseases: missing pieces in the jigsaw

The mechanisms involved in the pathogenesis of dengue hemorrhagic fever and dengue shock syndrome remain unresolved. Antibody-dependent enhancement of infection has long been thought to play a central role; however, this remains unverified. The alternative hypothesis that virus variation, virulence and dynamics may account for severe dengue disease, particularly in children, should be considered.     

Pathogenesis of scoliosis

Scoliosis often occurs in otherwise normal individuals or it may be associated with many widely differing diseases. The curve patterns are fairly uniform and the vertebrae always rotate in the frontal and horizontal planes producing convex side rotation with little displacement of the spinuous processes. Many small curves do not increase. Progressive scoliosis increases linearly and the rate of increase accelerates at puberty. No endocrine abnormalities have been observed in these patients. Usually the deformity is not caused by abnormal vertebral growth nor by abnormal collagen in verterbral ligaments. The glycosaminoglycans of nucleus pulposus are decreased in patients with idiopathic scoliosis. We speculate that loss of proteoglycans will affect the viscoelastic properties of the intervertebral discs which may result in permanent deformation. The etiology of scoliosis appears to be multifactorial with a genetic tendency to the deformity which is triggered in different individuals by different factors, some medical, some mechanical and some genetic.     

Pathogenesis of Wegener's granulomatosis

Although a single disease entity, Wegener's granulomatosis (WG) displays a set of clinical manifestations, each with a different immunopathogenesis. Granuloma formation, "pauci-immune" vasculitis and glomerulonephritis (= renal vasculitis) are the histologic hallmarks of WG which can occur together (WG triad) in full-blown disease, or separately in "initial phase" disease or the formes frustes. The different clinical manifestations are characterised by multiple immune abnormalities that culminate in the over-production of autoantibodies directed mainly against proteinase 3 (PR3-ANCA). A number of in vitro observations point to the potential mechanisms by which ANCA could induce neutrophil-mediated vascular injury, i.e. vasculitis. The most commonly postulated scenario for ANCA-mediated vasculitis involves the interaction of polymorphonuclear neutrophils (PMN) and endothelial cells (EC) via cell adhesion molecule interactions. The initiating event is ANCA-induced leukocyte activation, in which PMN-derived mediators (i.e. cytokines, lipid metabolites, etc.) are intimately involved. The result is necrotizing inflammation of blood vessel walls. However, the clinical and pathological hallmark of WG is the coexistence of vasculitis and granuloma. The causative agent(s) leading to granuloma formation, predominantly in the respiratory tract, is still unknown, but the presence of T cells in the granulomatous inflammation indicates T-cell hyperactivity. Immunohistochemical studies have shown that the cellular infiltrations in renal and pulmonary lesions of WG primarily contain CD4+ T-cells and macrophages. Recent investigations have demonstrated that CD4+ T-cells from granulomatous lesions in the nose and from bronchoalveolar lavage (BAL) mainly express the Th1 cytokine profile, which stimulates predominantly cell-mediated immune responses. This result supports the hypothesis that due to the two-phase course of WG there occurs a polarisation of the T-cell sub-population (Th1 versus Th2 type) which may explain the transition from the initial (granulomatous) phase of WG (so-called localized or locoregional restricted WG) to the generalized (vasculitic) phase. In conclusion, although the initiating events in the development of WG are still unknown, remarkable advances have been made in characterizing the infiltrating inflammatory cells and their products, which is of major importance in understanding the pathogenesis of this disease. In this regard, the use of specific mediators (i.e. cytokines, adhesions molecule antagonists, anti-Id ANCA, etc.) to modulate the inflammatory response may prove beneficial in the therapy of WG.     

Pathogenesis of diabetic microangiopathy

Several are the recent experimental data regarding the pathogenesis of diabetic microangiopathy, even if the comprehensive picture of this condition is still rather incomplete. The functional and structural alterations of several organs involved (first of all kidney and retina) are especially dependent on the activation of the polyol pathway and on the increase of the nonenzymatic glycosylation. An important determinant of diabetic microangiopathy is the increase of permeability, at first charged especially to the haemodynamic alterations and partly reversible, and later supported by irreversible variations of the cellular and extracellular components of the vascular wall. Genetic factors certainly contribute to the explanation of the diverse gravity of microvascular damage in diabetic patients, even if the mechanisms by which they interfere are only partly known. Furthermore, the links between arterial hypertension and diabetic nephropathy, and also the reduction in glycosaminoglycans in the basal membranes are perhaps genetically originated.     

Pathogenesis of IgA nephropathies

The loss of kidney function in IgA nephropathy results from matrix overproduction by mesangial cells stimulated by IgA circulating complexes (IgA-CC) deposited in the mesangial area. High IgA-CC plasma concentrations are at least partly secondary to a genetically induced overproduction of undergalactosylated IgA molecules poorly cleared by the liver.     

Pathogenesis of Crohn''s disease

There remains a great deal to be accomplished in freeing many millions of gays and lesbian from the tyranny of fear of discovery, of actual and potential economic disenfranchisement, of the burden of ridicule, shame, and scorn, and of penalties for alleged criminal behavior. Nevertheless, the recognized status, for example, of openly gay and lesbian psychologists ... is light years away from their inferior and almost certainly closed status of 1954. They are not only free now of the criminal penalties and of the stigma of mental illness, but are in positions of trust, respect, and power.     

Pathogenesis of leukocytoclastic vasculitis

A prospective protocol for the management of the airway was applied to patients in the ICU. Acute complications due to intubation and tracheotomy as well as laryngo-tracheal lesions were studied in 125 consecutive patients during one year from the moment of extubation. Thirty four cases (27%) needed reintubation, and 58 tracheotomies were performed (46%). The average length of intubation was of 10 +/- 7 days. Sixty five patients (53%) had acute complications due to intubation and 30 (52%) had acute complications due to the traccotomy. The high incidence of laryngo-tracheal lesions in the 85 patients who underwent early exploration (76 cases [90%]) was reduced in those who underwent late exploration (11 cases [20%]). Analysis of possible prognostic factors in the development of late lesions allows us to affirm that a reduction in the length of intubation diminishes the presence of late lesions. We recommend the avoidance of oro-tracheal intubation prolonged for more than 10 days by the early carrying out of tracheotomy.