Characteristics of human erythrocyte insulin receptors

Highly specific insulin receptors have been identified on human erythrocytes. A modification of the monocyte insulin radioreceptor technique permitted distinct separation of human erythrocytes with their bound insulin from the free insulin. When incubated with 80 pg. per milliliter of 125I-insulin (pH 8.0, 3.5 hours, 15 degrees C.), erythrocytes from 17 normal volunteers specifically bound 10 per cent (+/- 1.450 S.D.) of the total 125I-insulin. Less than 15 per cent of the total 125I-insulin bound was nonspecific. Binding of 125I-insulin to human erythrocytes was dependent on pH and temperature. Less than 5 per cent of the insulin available to the plasma membrane was degraded. Both calcium and magnesium enhanced 125I-insulin binding by 100 per cent but had no synergistic effect when mixed in a 1:1 molar ratio. Scatchard analysis of the binding data resulted in a curvilinear plot with characteristics typical of negative cooperative interactions between receptor sites and with an unoccupied site affinity constant of 0.1 X 10(8) M-1. Human erythrocytes have 2,000 insulin binding sites per erythrocyte with 14 sites per square micrometer of surface area. The readily available human erythrocyte, thus, has both specific insulin binding sites and binding characteristics similar to other human cell types. These studies have provided the basis for further clinical investigation of polypeptide hormone receptors on human erythrocytes.     

An audit of clinical resources available for the care of head and neck cancer patients in England

OBJECTIVE: To undertake a postal survey of cancer networks to define the services available for the diagnosis, treatment and support of patients with head and neck cancer in England. FINDINGS: Thirty-four cancer networks are now responsible for the delivery of head and neck cancer services in England and 52 cancer units responded to our questionnaire. Multidisciplinary team working was evident in all centres. However such team working was not always fully staffed, especially in areas of national staff shortages such as pathology, radiology, dietetics and speech therapy. Rapid referral pathways were present for initial assessment of patients but clinically significant delays were identified in the provision of complex investigations, in access to intensive care beds and for oncological care--especially radiotherapy. CONCLUSIONS: Major changes in service configuration are likely to be required if the current national targets of time to diagnosis and treatment are to be met.     

Pathologic changes of presbycusis begin in secondary processes and spread to primary processes of strial marginal cells

Strial atrophy underlying age-related hearing loss was investigated by ultrastructural comparisons in young and senescent gerbils. In young animals strial marginal cells (MCs) projected primary processes which gave rise to and were connected by numerous ultrathin secondary processes. In 30-36-month-old gerbils, the MC secondary processes degenerated into lamellar or amorphous profiles as the first manifestation of strial atrophy. Some short primary processes shorn of projecting and connecting secondaries coalesced to form mitochondria-filled lobules. Strial involution appeared to progress with transformation of the degenerating processes and lobules into permanent residues of laminated amorphous substance. A second apparently unique form of degeneration was observed in which areas filled with homogeneous granular material replaced the processes that comprise the basal half of the normal MC. An abrupt line of transition separated this structureless degradation product below from the viable upper half of the MC. The terminally involuted stria consisted of MC bodies lining scala media, along with vestigial remnants of MC processes, nearby normal appearing intermediate cells (ICs) and unaltered basal cells. The only age-related change in ICs involved incorporation of melanosomes into very large, matrix-filled lysosomes. A profile of one MC in apparent necrosis provided evidence for an infrequent occurrence of MC death. These data support a progression of pathologic changes beginning with the demise of MC secondary processes and ending with ablation of secondary and primary processes. The initial injury apparently occurs as a result of oxidative self-damage to mitochondria in the MCs primary processes, leading to insufficient ATP for the Na,K-ATPase of the secondary processes. The reduced ATP level may cause cytotoxic alteration of the cytosolic Na(+)/K(+) ratio first in MC secondary processes and later in the primaries, with consequent degeneration of these structures.     

Fungal rhinosinusitis: state-of-the-art diagnosis and treatment

The past 30 years has been witness to a period of tremendous growth and innovation within the field of rhinology, facilitating a better understanding and improved management techniques for a variety of local and systemic conditions manifesting within the nose and paranasal sinuses. Of these disease states, the spectrum of conditions considered under the rubric of fungal rhinosinusitis best exemplifies modern rhinology's position as a truly multidisciplinary specialty. We review the classification of the various forms of fungal rhinosinusitis and their clinical presentations, radiologic findings, and treatment options.     

Transient phenomena in learning and evolution: genetic assimilation and genetic redistribution

Deacon has recently proposed that complexes of genes can be integrated into functional groups as a result of environmental changes that mask and unmask selection pressures. For example, many animals endogenously synthesize ascorbic acid (vitamin C), but anthropoid primates have only a nonfunctional version of the crucial gene for this pathway. It is hypothesized that the loss of functionality occurred in the evolutionary past when a diet rich in vitamin C masked the effect of the gene, and its loss effectively trapped the animals in a fruit-eating lifestyle. As a result, the complex of abilities that support this lifestyle were evolutionarily bound together, forming a multilocus complex. In this study we use evolutionary computation simulations to explore the thesis that masking and unmasking can transfer dependence from one set of genes to many sets, and thereby integrate the whole complex of genes. We used a framework based on Hinton and Nowlan's 1987 simulation of the Baldwin effect. Additional gene complexes and an environmental parameter were added to their basic model, and the fitness function extended. The simulation clearly demonstrates that the genetic redistribution effect can occur in silico, showing an initial advantage of endogenously synthesized vitamin C, followed by transfer of the fitness contribution to the complex of genes that together allow the acquisition of vitamin C from the environment. As is well known in the modeling community, the Baldwin effect only occurs in simulations when the population of agents is 'poised on the brink' of discovering the genetically specified solution. Similarly, the redistribution effect occurs in simulations under specific initial conditions: too little vitamin C in the environment, and its synthesis it is never fully masked; too much vitamin C, and the abilities required to acquire it are not tightly integrated. The Baldwin effect has been hypothesized as a potential mechanism for developing language-specific adaptations like innate universal grammar and other highly modular capacities. We conclude with a discussion of the relevance of genetic assimilation and genetic redistribution to the evolution of language and other cognitive adaptations.