Select types of supporting cell in the inner ear express aquaporin-4 water channel protein

Aquaporins (AQPs) confer a high water permeability on cell membranes and play important parts in secretory and absorptive epithelia in kidney and other organs. Here we investigate whether AQPs are expressed in the sensory epithelia of the inner ear, where a precise volume regulation is crucial. By use of specific antibodies it was found that the inner ear contains AQP1 and 4 while being devoid of detectable levels of AQP2, 3 or 5. Immunofluorescence and postembedding immunogold labelling revealed a strictly non-epithelial distribution of AQP1, confirming previous data. In contrast, AQP4 protein and mRNA (visualized by in situ hybridization) were concentrated in select types of supporting cell, including Hensen's cells and inner sulcus cells. Immunogold particles signalling AQP4 were confined to the basolateral plasma membrane of Hensen's cells and to the basal plasma membrane of Claudius cells and inner sulcus cells. AQP4 was also found in supporting cells of the vestibular end organs, but was absent from transitional epithelial cells and dark cells. Strong labelling for AQP4 and AQP4-mRNA was associated with the central part of the cochlear and vestibular nerves. Hair cells were consistently unlabelled. Our findings indicate that AQP4 may facilitate osmotically driven water fluxes in the sensory epithelia of the inner ear and thus contribute to the volume and ion homeostasis at these sites.     

Distribution of glutamine-like immunoreactivity in the cerebellum of rat and baboon (Papio anubis) with reference to the issue of metabolic compartmentation

Summary The cellular and subcellular localization of glutamine, a major glutamate precursor, was studied by means of an antiserum raised against glutaraldehydefixed glutamine. Ultrathin sections from the cerebellar cortex of rat and baboon (Papio anubis) were incubated sequentially in the primary antiserum and in a secondary antibody coupled to colloidal gold particles. The labelling intensity was quantified by computer-aided calculation of gold particle densities. High levels of immunoreactivity occurred in glial cells (Bergmann fibres, astrocytes, and oligodendrocytes), intermediate levels in cell bodies and processes of granule cells, and low levels in terminals of presumed GABAergic or glutamatergic fibres (terminals of basket and Golgi cells, and of parallel, mossy, and climbing fibres). The labelling intensity of Purkinje cells showed some variation, but never exceeded that in glial cells. Within the nerve fibre terminals, the glutamine-like immunoreactivity showed some preference for mitochondria, but was otherwise evenly distributed. The predominant glial localization of glutamine was also obvious in light microscopic preparations processed according to the postembedding peroxidase-antiperoxidase procedure. Gold particle densities over different types of profile in glutamine immunolabelled sections were compared with particle densities over the corresponding types of profiles in neighbouring sections labelled with an antiserum to glutaraldehyde-fixed glutamate. The glutamate/glutamine ratio, expressed arbitrarily by the ratio between the respective gold particle densities, varied by a factor of about 6, with the highest ratio in the putative glutamatergic mossy and parallel fibre terminals, and the lowest ratio in glial elements. The remaining tissue components displayed intermediate ratios. The present study provides direct morphological evidence for the existence in the brain of distinct compartments with differing glutamate/glutamine ratios.This paper is dedicated to Professor Fred Walberg on the occasion of his 70th birthdayOn leave of absence from Department of Anatomy, Capital Institute of Medicine, You An Men Street, Beijing, China     

Mechanisms of nonopsonic phagocytosis of Pseudomonas aeruginosa.

The interaction of the macrophage cell line P388D1 with Pseudomonas aeruginosa in the absence of stimulators or opsonins led to substantial association of bacteria, as judged by visual counting and FACScan assays. This association was observable within 5 min of addition of bacteria, could not be disturbed by exhaustive washing, and occurred with pilus- or flagellum-deficient mutants but not with rpoN mutants, which have been proposed to lack a secondary adhesin. In contrast, specific antibody was capable of causing similar enhancement of bacterial uptake regardless of the rpoN phenotype. Fibronectin stimulated uptake of bacteria with the pilus as an adhesin, and stimulation was observable within 5 min. Both fibronectin-enhanced and antibody-opsonized uptake were susceptible to inhibition by pertussis toxin but not by cholera toxin. The influence of fibronectin on P388D1 cells was distinguishable from that of lipopolysaccharide, which caused substantial morphological changes in cells. Although lipopolysaccharide stimulated bacterial uptake, it actually suppressed fibronectin-mediated enhancement of uptake at high concentrations.     

Quantitative determination of cell surface β-adrenoceptors in different rat skeletal muscles

In the present study, the density of cell surface beta-adrenergic receptors was determined in different skeletal muscles using the hydrophilic ligand [3H]CGP 12177. The density of beta-adrenergic receptors was highest in the slow-twitch soleus muscle (32.8+/-0.9 fmol mg dw(-1)) and lowest in the fast-twitch glycolytic white gastrocnemius (10.4+/-0.5 fmol mg dw(-1)) beta-Adrenoceptor density correlated closely with the percentage of type-I fibres (r=0.979; P<0.0001) and inversely with the percentage of type-IIB fibres (r=696; P<0.03). Incubation with isoprenaline (10 microM) for 30 min decreased the density of beta-adrenergic receptors in the cell surface from 32.9+/-0.8 to 19.3+/-0.7 fmol mg dw(-1) in the soleus and from 16.8+/-1.0 to 12.0+/-0.7 fmol mg dw(-1) in the epitrochlearis. Internalisation appeared rapid (half-time less than 5 min). To study externalisation of beta-adrenergic receptors, soleus strips were incubated 30 min with 10 microM isoprenaline and then transferred to buffer without agonist. The first incubation reduced the density to approximately 50%, the subsequent incubation without agonist increased cell surface receptor density to approximately 80% of the initial density after 1 h. No further increase was observed over the next 2 h, suggesting that some of the receptors had been degraded. Insulin or contractile activity did not influence rate of externalisation.     

Squamous cell carcinomas of the head and neck in Norway, 1953-92: an epidemiologic study of a low-risk population

Trends in incidence, five-year relative survival, and mortality among patients in Norway with squamous cell carcinoma of the oral sites, oro-/hypopharynx, and larynx were studied for the period 1953-92. Throughout the first part of the study period, age-adjusted incidence rates (AAIR) of oral cancer remained stable in both genders. Since the end of the 1960s, AAIRs increased by 13 percent per five-year period in males and 12 percent in females. The figures suggest increased male incidence rates of oral cancer in younger age groups. During the same period, AAIRs of cancers of the oro-/hypopharynx in males increased by 19 percent per five-year period. The AAIRs of laryngeal cancer increased steadily from 1953-92 among both males and females by 17 percent and 21 percent per five-year period, respectively. For all sites, changes in AAIRs for males were greater in rural than in urban areas. No improvement in detection of disease at a localized stage was observed for either gender. There are indications of improvements in the five-year relative survival rates for oral and pharyngeal cancer in both genders. For all sites, relative survival was better in younger than in older patients. Only in the case of pharyngeal cancer in males was an increase in disease-specific mortality rates positive for a time trend.     

The genetics of congenital aniridia—a guide for the ophthalmologist

Congenital aniridia is a rare panocular disease caused by fundamental disturbances in the development of the eye, characterized primarily by hypoplasia of the iris and macula. Severe secondary complications such as keratopathy, cataract, and glaucoma are common and often lead to considerable visual impairment or blindness. Many complications in aniridia patients are difficult to treat and present a challenge for the ophthalmologist. Increasingly, associated nonocular features of the disease are also being recognized. Over the past decades, major steps have been made in the understanding of the genetic basis of aniridia. Moreover, recent studies have prepared the ground for future treatment options based on specific mutations. Therefore, specific knowledge about genetics in aniridia has become more important than ever. We provide an overview of the field of aniridia genetics and its clinical implications.     

Clinical significance of the WHO grades of follicular lymphoma in a population-based cohort of 505 patients with long follow-up times

The prognostic value of grading follicular lymphoma has been debated since the 1980s. There is consensus that World Health Organization (WHO) grades 1 and 2 are indolent, but not whether grades 3A or 3B are aggressive. We retrospectively reviewed the follicular lymphoma diagnoses according to the 2008 WHO classification in all diagnostic specimens from a population-based cohort of 505 patients with a median follow-up time of 10·0years (range, 4·6-16·0). After excluding 43 patients with concomitant diffuse large B-cell lymphoma, 345 remained with grade 1-2, 94 with grade 3A, and 23 with grade 3B follicular lymphoma. Grades 1-2 and 3A seemed equally indolent, with indistinguishable clinical courses, even in patients receiving anthracyclines. Compared with grades 1-3A and independently of clinical factors, grade 3B correlated with higher mortality (P=0·008), but outcome was improved after upfront anthracycline-containing therapy (P=0·015). In contrast to grade 1-3A patients, grade 3B patients experienced no relapses or deaths beyond 5years of follow-up. Furthermore, patients with grade 3B were predominantly male and seldom presented with bone-marrow involvement. We conclude that follicular lymphoma grade 1-3A is indolent and incurable with conventional therapy. Grade 3B appears to be an aggressive but curable disease.     

Expression of CD18 (integrin β2 chain) correlates with prognosis in malignant B cell lymphomas

Summary. Several studies have shown that cell cycle related parameters including DNA synthesis and activation antigen expression can predict patient survival in lymphoma patients. In this study of 69 malignant B cell lymphomas we have examined the cell surface expression of several cell interaction and activation molecules by flow cytometry. Expression of CD18 (integrin β₂ chain) was found to correlate strongly with patient survival (median follow up 50 months) even when adjusting for other important prognostic factors ( P = 0.0001). The percentage of cells positive for CDw75 proved important both as a single parameter and in the multivariate analysis. Histology, classified as low versus high grade malignancy, bulky versus not bulky disease and high versus low thymidine incorporation, was also found to correlate with prognosis in this study.