D-[3H]galactose incorporation into glycogen in retinal cone cells

Previous studies have shown that bovine retinas incubated with [3H]galactose incorporated it, unmodified, into large molecules. Light and electron microscope autoradiography showed a significant proportion of the label to be in cone inner segments, and pulse-chase studies showed it was subsequently transported to the synaptic pedicles. In this report, evidence is presented to show that the galactose-labelled macromolecules are resistant to hydrolysis by proteolytic enzymes, testicular hyaluronidase, chondroitinase ABC, beta-glucosidase and beta-glucuronidase, but are readily degraded by alpha-amylase and beta-galactosidase, and to a lesser extent by beta-amylase. Treatment with alpha-amylase also leads to specific removal of radioactivity from cone inner segments and pedicles, as judged by light-microscopic autoradiography. These studies appear to indicate that the cone-specific galactose label is in glycogen or glycogen-like molecules.     

To what extent does IQ 'explain' socio-economic variations in function?

Background  

The aims of this study were to examine the extent to which higher intellectual abilities protect higher socio-economic groups from functional decline and to examine whether the contribution of intellectual abilities is independent of childhood deprivation and low birth weight and other socio-economic and developmental factors in early life.     

Discordant repeat size and phenotype in Kennedy syndrome

Previous reports in the literature have described correlation of increasing repeat length with severity of the phenotype, in Kennedy syndrome. We describe male siblings with different repeat lengths, with lack of expression of the phenotype in the sibling with the longer repeat length. The phenotype was identical to motor neurone disease. There is variability of expression in Kennedy syndrome and repeat length even in siblings cannot be taken as a conclusive indicator of severity. CAG repeat length cannot be used to predict the natural history of Kennedy disease. The diagnosis of Kennedy syndrome should be considered in male patients presenting with atypical motor neurone disease.     

INTERFERONS IN ONCOLOGY

SUMMARY The interferons are natural glycoproteins secreted in response to various stimuli, including viral infection. They have antiviral, antiproliferative and immunomodulatory effects on different target cell populations. Since recombinant human interferons have become available, they have been tested in a wide range of malignancies. They are well established in the treatment of hairy cell leukaemia, chronic myelogenous leukaemia and multiple myeloma. Although they have documented activity against lymphoma, melanoma, renal cell cancer and carcinoid tumours, their role in the treatment of these tumours is less clear. In the common solid tumours, such as lung cancer and colorectal cancer, the use of interferons remains experimental. Here we will summarise their practice applications in oncology, using randomised studies where available to establish their place in multi-modality treatment. We will not discuss their use as antiviral or immunomodulating agents in viral and autoimmune diseases, multiple sclerosis or after organ transplantation.     

Contrasting effects of propranolol on sympathetic nerve activity and vascular resistance during orthostatic stress.

BACKGROUND. Previous studies in humans advanced the concept that cardiac filling pressure and contractility, the primary determinants of ventricular mechanoreceptor discharge, are important determinants of sympathetic outflow during orthostatic stress. Thus, intravenous propranolol greatly attenuated forearm vasoconstrictor response to venous pooling with lower body negative pressure (LBNP). The aim of this study was to reevaluate the experimental support for this concept by using direct measurements of sympathetic nerve activity. METHODS AND RESULTS. In 11 healthy humans, we recorded muscle sympathetic nerve activity (MSNA) with microelectrodes (peroneal nerve), as well as blood flow in the forearm and calf (venous occlusion plethysmography) at baseline and during graded LBNP. The same experiments were repeated after administration of propranolol (0.15 mg/kg i.v.), which is thought to decrease ventricular mechanoreceptor discharge. The major new findings are that propranolol neither increased baseline MSNA nor attenuated the increases in MSNA during graded orthostatic stress even though in the same subjects, propranolol simultaneously increased the baseline level of vascular resistance in both the forearm and calf and substantially attenuated the increases in regional vascular resistance during orthostatic stress. CONCLUSIONS. Systemic beta-blockade causes a marked dissociation between sympathetic outflow and vascular resistance that invalidates the use of intravenous propranolol as an experimental model to examine the reflex effects of ventricular mechanoreceptors on peripheral vascular resistance in humans.