Ganglioside modulation of lipopolysaccharide-initiated complement activation

Highly purified preparations of mouse gangliosides have been demonstrated to bind to purified preparations of lipopolysaccharide (LPS). In some instances, the binding has been demonstrated to be dependent upon the presence of sialic acid in the ganglioside preparation. The binding of gangliosides to LPS from the deep rough Salmonella minnesota Re mutant has suggested that the interaction involves the lipid A-2-keto-3-deoxyoctulosanate region of the LPS macromolecule. The interaction between gangliosides and LPS has been demonstrated to result in an abrogation of lipid A dependent activation of the classical pathway of serum complement by Re LPS. Surprisingly, however, the presence of sialic acid containing glycolipids has been shown to enhance significantly the capacity of LPS to initiate activation of the alternative pathway of complement. These data suggest that sialic acid can enhance as well as inhibit the formation of a stable alternative-pathway C3 convertase.     

Psychological and neuropsychological aspects of COPD

A review of the literature dealing with the effects of chronic obstructive pulmonary disease (COPD) on psychological and neuropsychological functioning indicates that significant emotional and adaptive deficits characterize this patient population. Psychiatric consultation can provide valuable assistance to the primary care physician by reducing emotional distress and correcting dysfunctional attitudes and beliefs. Neuropsychological assessment can elucidate an individual's neurobehavioral resources and deficits.     

Unusual combinations of verbal and performance IQs in normal and neurologically impaired elderly.

For the WAIS-R old age standardization sample, unusual Verbal-Performance IQ combinations were generated at the .05 and .01 levels of significance. In a preliminary attempt to determine the neurological significance of these unusual test score combinations, the standardization based values were compared to those of a small sample of elderly brain-injured subjects. The frequency of unusual IQ combinations was essentially the same for the normal and brain-damaged elderly. Unusual VIQ-PIQ combinations should not be considered pathognomonic of neurological impairment.     

Sequence variation and size ranges of CAG repeats in the Machado-Joseph disease, spinocerebellar ataxia type 1 and androgen receptor genes

A subgroup of trinucleotide repeat diseases result from abnormalexpansions of CAG repeats which are translated into polyglutaminestretches. As yet there is little understanding of how the polyglutaminesfunction either normally, or when expanded. We have investigatedthese sequences in the Machado-Joseph disease, androgen receptorand spinocerebellar ataxia type 1 genes in humans and otherprimates. None of the 748 normal chromosomes that were examinedhad more than 34 uninterrupted gluta-mine codons in the Machado-Josephdisease gene. Similarly, no normal alleles with more than 39uninterrupted glutamine codons have been reported for the otherdisease genes associated with polyglutamine expansions. Sequenceanalyses of the repeats in primates revealed shorter polyglutaminestretches in some of the non-human primates at all three lociand marked diversions from the expected polyglutamines in theorang-utan Machado-Joseph gene and in the marmoset spinocerebellarataxia type 1 gene. These data suggest that conservation ofthese polyglutamine stretches may not always be necessary fornormal gene function.     

Origin of myofibroblasts in the avascular capsule around free-floating intraperitoneal blood clots

The origin of cells comprising the capsule which forms around free-floating intraperitoneal blood clots has been examined in rats. One day after implantation the surface of the clot was covered by 1-2 layers of rounded nucleated cells. The majority of these cells were monocyte/macrophage in type with many cytoplasmic folds. Over the next 2 wk a thick capsule composed of dense connective tissue and myofibroblasts developed, completely covering the clot. The surface became covered by a contiguous layer of mesothelial cells, apparently derived from displaced cells of the damaged peritoneum. Detailed examination of the formation of the capsule suggested that a proportion of cells with the characteristic features of peritoneal macrophages gradually develop over a 3-4 d period the characteristic features of fibroblasts. These cells with time then develop filament bundles and a basal lamina to become myofibroblasts.     

Rats fed only during the light period are resistant to stress-induced weight loss

Repeated restraint stress (3 h/day for 3 days) causes a chronic down-regulation of body weight in rats. This study determined whether weight loss was influenced by the time of day that rats had access to food or that stress was applied. Groups of male Sprague-Dawley rats were fed a 40% kcal fat diet with food given ad libitum, only during the light phase or only during the dark phase. After 2 weeks of adaptation, rats within each feeding treatment were divided into four groups. One was exposed to repeated restraint at the start of the light phase, another was restrained at the start of the dark phase and the remaining groups were nonstressed controls for restrained rats. Body weight was significantly reduced in ad libitum- and dark-fed restrained rats, compared with nonstressed controls, from Day 2 of restraint, regardless of the time of day that they were stressed. There was no significant effect of restraint on weight change of light-fed rats. Food intake was inhibited by stress in ad libitum- and dark-fed rats, but it was not changed in light-fed rats. Serum corticosterone was increased by restraint in all rats irrespective of feeding schedule. This study demonstrates that stress-induced weight loss only occurs when rats have food available during their normal feeding period (dark phase) and is not determined by increased corticosterone release.     

Modeling pandemic preparedness scenarios: health economic implications of enhanced pandemic vaccine supply

Influenza pandemic planning is a complex, multifactorial process, which involves public health authorities, regulatory authorities, academia and industry. It is further complicated by the unpredictability of the time of emergence and severity of the next pandemic and the effectiveness of influenza epidemic interventions. The complexity and uncertainties surrounding pandemic preparedness have so far kept the various stakeholders from joining forces and tackling the problem from its roots. We developed a mathematical model, which shows the tangible consequences of conceptual plans by linking possible pandemic scenarios to health economic outcomes of possible intervention strategies. This model helps to structure the discussion on pandemic preparedness and facilitates the translation of pandemic planning concepts to concrete plans. The case study for which the model has been used shows the current level of global pandemic preparedness in an assumed pandemic scenario, the health economic implications of enhanced pandemic vaccine supply and the importance of cell culture-based influenza vaccine manufacturing technologies as a tool for pandemic control.