The effect of human monocytes and macrophages on lymphocyte proliferation

The formation and dissociation of BSA:anti-BSA complexes was studied under two dissociating conditions: (i) low pH, which disrupts Coulombic bonds, and (ii) low surface tension, which disrupts van der Waals bonds. Soluble complexes formed in marked (thirty-two times) antigen excess were almost totally dissociated at low pH. By contrast, complexes formed near equivalence or in the zone of antibody excess, while becoming smaller, were not dissociated at low pH. Lowering surface tension at neutral pH likewise resulted in smaller complexes but not in dissociation of antigen from antibody. Dissociation of complexes formed near equivalence or in antibody excess was achieved by simultaneously lowering pH and surface tension. These data suggest that complexes formed in marked antigen excess involve predominantly Coulombic bonding while complexes formed at other antigen:antibody ratios involve both Coulombic and van der Waals bonding.     

The mutual clonal origin of the lymphoplasmocytic and lymphoma cell in alpha-heavy chain disease.

Biosynthetic studies in alpha-heavy chain disease were performed on the gut tumour which was composed mainly of lymphoplasmocytic cells and on the mesenteric lymph node tumour composed mainly of immunoblasts. The gut tumour cells synthesised alpha-heavy chains and secreted them during 2-5 hr culture, whereas the lymph node tumour cells synthesized alpha-heavy chains which were shed into the culture medium only after 20 hr. These chains were shown to be present on the surface of the immunoblastic tumour cells by enzymatic radioiodination. Both the surface and the secreted alpha-heavy chain of the lymph node and gut tumour were found to be smaller than the alpha-heavy chain of myeloma proteins. These results suggest that the lymphoblasmocytic and the immunoblastic tumour cells originate from the same defective clone.     

Gene dosage and down's syndrome: Metabolic and enzymatic changes in PC12 cells overexpressing transfected human liver-type phosphofructokinase

Down's syndrome (DS) is a human genetic disease caused by triplication of the distal third of chromosome 21 and overexpression of an unknown number of genes residing in it. The gene for the liver-type subunit of phosphofructokinase (PFKL), a key glycolytic enzyme, maps to this region and the product is overproduced in DS erythrocytes and fibroblasts. These facts, together with abnormalities which occur in DS glycolysis, make PFKL overexpression a candidate for causing some aspects of the DS phenotype. A cellular model for examining the consequences of PFKL overexpression in DS was constructed by transfecting rat PC12 cells with the human PFKL cDNA. Phosphofructokinase (PFK) isolated from PFKL-overexpressing clones was more inhibited by ATP and citrate and less activated by fructose-6-phosphate than control PFK; similar results were obtained when PFK preparations from DS and control fibroblasts were compared. In vivo NMR measurements determined that cells overexpressing PFKL performed glycolysis 40% faster than controls. These results show that overexpression of PFKL is the cause for altered biochemical regulatory characteristics of PFK in DS fibroblasts and can result in enhancement of glycolysis rates. It is also shown that increased gene dosage can exert its influence not merely by enhancing the amounts of gene products but also by altering their biochemical nature.     

An evaluation of the U.S. Army fallout prediction model

The U.S. Army fallout prediction method was evaluated against an advanced fallout prediction model--SIMFIC (Simplified Fallout Interpretive Code). The danger zone areas of the U.S. Army method were found to be significantly greater (up to a factor of 8) than the areas of corresponding radiation hazard as predicted by SIMFIC. Nonetheless, because the U.S. Army's method predicts danger zone lengths that are commonly shorter than the corresponding "hot line distances" of SIMFIC, the U.S. Army's method is not reliably conservative.     

Comparative study of in vitro and in vivo modulation of lactogenic and somatotropic receptors by native human growth hormone and its modified analog prepared by recombinant deoxyribonucleic acid technology

A modified analog of human GH (hGH), prepared by recombinant DNA technology, that lacks 13 amino acids at the amino terminus (Met14hGH), was able to compete with [125I]hGH for binding to lactogenic receptors in Nb2-11C rat lymphoma cells, to somatotropic receptors in IM-9 human lymphocytes, and to both lactogenic and somatotropic receptors in the microsomal fraction of virgin female rat liver. Exposure of intact Nb2 or IM-9 cells to Met14hGH did not reduce the number of surface or intracellular receptors, as compared to the control without hormone. A parallel exposure to 500-fold lower concentrations of hGH resulted in 77-93% reduction in both surface and intracellular receptors. In contrast to [125I]hGH, [125I]Met14hGH was not taken up by the intact Nb2 lymphoma cells. Infusion of anesthetized female virgin rats for 3 h with hGH down-regulated both lactogenic and somatotropic receptors in the liver. A similar infusion with up to 200-fold higher amounts of Met14hGH did not lower the number of total receptors, indicating lack of down-regulation. Some decrease in the binding to free receptors was observed, suggesting that Met14hGH is capable of binding to liver receptors in vivo.     

Sleep characteristics in children with Down syndrome.

BACKGROUND: Obstructive sleep apnea syndrome is common in children with Down syndrome (DS). Little is known about sleep patterns, especially arousals, awakenings, and movements during sleep in children with DS. OBJECTIVE: To determine the characteristics of sleep disorders in children with DS and to define the associations between respiratory disturbance and arousals, awakenings, and movements. METHODS: The study included 23 children with DS, compared with 13 children with primary snoring. All underwent a 6- to 8-hour sleep study. RESULTS: The respiratory disturbance index was significantly higher in the children with DS (2.8 +/- 2.3 events/h vs 0.6 +/- 0.4 events/h; P <.05). Sleep was significantly fragmented in children with DS, who had a significantly higher arousal/awakening (A/Aw) index (24.6 +/- 7.9 events/h) compared with the comparison group (17.6 +/- 4.0 events/h) (P <.02). A higher percentage of jerks associated with A/Aw and respiratory event-associated A/Aw was observed in patients with DS (45.2% +/- 25% and 8.6% +/- 6.4%, respectively) compared with the control patients (10.2% +/- 4.5% and 1.5% +/- 2.1%) (P <.02). The median length of occurrences of stage 2 sleep was 27% shorter in the DS group (P <.03). The number of shifts from "deeper" to "lighter" stages of non-rapid eye movement sleep was 30% greater (P <.02) in the DS group. CONCLUSION: Children with DS have significant sleep fragmentation, manifested by frequent awakenings and arousals, which are only partially related to obstructive sleep apnea syndrome.     

From genome to antivirals: SARS as a test tube

The severe acute respiratory syndrome (SARS) epidemic brought into the spotlight the need for rapid development of effective anti-viral drugs against newly emerging viruses. Researchers have leveraged the 20-year battle against AIDS into a variety of possible treatments for SARS. Most prominently, based solely on viral genome information, silencers of viral genes, viral-enzyme blockers and viral-entry inhibitors were suggested as potential therapeutic agents for SARS. In particular, inhibitors of viral entry, comprising therapeutic peptides, were based on the recently launched anti-HIV drug enfuvirtide. This could represent one of the most direct routes from genome sequencing to the discovery of antiviral drugs.     

Effects of UV-A irradiation on lens morphology and optics

Epidemiological studies have indicated that ultraviolet radiation (UVR) is one of the main factors leading to senile cataract formation. We investigated morphological changes in the eye lens caused by UVR-A. Twenty three pairs of lenses obtained from 23 one-year-old calves were used for this study. For each pair, one lens was exposed to 44 J/m(2) UVR in the 365 nm wavelength region while the contralateral lens was not exposed and served as a control. The lenses were placed in specially designed organ culture containers for pre-incubation. Lenses were exposed to UVR after one day in culture. After irradiation, lens optical quality was monitored throughout additional 15 days of the culture period and lenses were taken for morphological analysis by scanning electron microscopy. Damage to lens optical quality was evident as early as day 8 after the irradiation and increased with time in culture. We found irregularity of fiber morphology in lenses exposed to UV-A irradiation (but not in control lenses), similar to that reported previously for aged lenses. At the end of the culture period (day 16), lens fiber membranes also showed holes in fiber membranes. We conclude that UVR-A caused damage to cell membranes of the lens and alterations in lens optics, which may subsequently lead to senile cataract formation.