Submaximal exercise in emphysema and malnutrition at two levels of carbohydrate and fat intake

Eight malnourished patients with emphysema (EMPH) and eight malnourished patients without evidence of lung disease (MLAN) received an infusion of 5% dextrose plus electrolytes (D5W) for 48 h and were then randomly assigned to a hypercaloric diet with either 53% of the calories as carbohydrate (CB) or with 55% as fat (FB) for the 1st wk, maintaining a constant protein intake. The alternate diet was given the following week. Ventilation and gas exchange were measured during supine cycle ergometry at 0, 12, and 25 W during the D5W, CB, and FB diet periods. At each exercise intensity, the EMPH group demonstrated a 12-15% greater O2 consumption, a lower respiratory quotient, and an O2 debt larger than that of the MALN group. Resting ventilation was higher during the CB than FB regimen in both groups of patients, but during the CB diet the EMPH group had a more exaggerated ventilatory response than the MALN group. The results demonstrate that EMPH patients have an unusual metabolic pattern during hypercaloric feeding and exercise. Furthermore in EMPH patients a FB regimen does not appear to create the additional stress on the respiratory system during exercise that is generated with a CB regimen.     

Mouse mammary tumor virus-related sequences in mouse lymphocytes are inducible by 12-O-tetradecanoyl phorbol-13-acetate

cDNA libraries from EL-4 cells treated with 12-O-tetradecanoyl phorbol-13-acetate (TPA) were screened for TPA-inducible sequences by differential hybridization. The most abundant inducible species was a sequence similar to that of mouse mammary tumor virus (MMTV). Induction of the mRNA corresponding to the MMTV-related sequences was already evident 30 min after TPA treatment, whereas the maximum accumulation occurred after 20 h of exposure to TPA. TPA also increased levels of MMTV-related RNA in the normal spleen cells of BALB/c and C57BL/6 mice. The level of RNA expression corresponding to MMTV-related sequences, however, was markedly elevated in EL-4 cells as compared with normal spleen cells. Southern blots of EL-4 cell DNA showed that the MMTV-related sequences were inserted into multiple locations of the EL-4 genome. Sequence analysis revealed that the MMTV-related cDNA clones included a part of the env gene and the right long terminal repeat of MMTV. However, the cDNA sequences were substantially different from published MMTV proviral sequences, most notably because of a contiguous deletion of 491 base pairs in the open reading frame within the U3 region.     

Construction of lambda gt103, a derivative of phage lambda gt10 that has unique EcoRI, NotI, SacI and SpeI sites and retains positive selection for recombinants.

A phage vector, lambda gt103, that has unique EcoRI, NotI, SacI and SpeI sites within the imm434 cI repressor gene, was constructed by PCR-aided site-directed mutagenesis of lambda gt10 [Huynh et al., DNA Cloning Techniques: A Practical Approach, 1985, pp. 49-78]. This vector allows directional cloning and retains positive selection for recombinants on Escherichia coli C600hfl strains (since only phages with disrupted cI genes plate on this host). Libraries made with this phage vector can be efficiently screened for clones in which a part of the insert is homologous to probe DNAs derived from a plasmid-based library, without cross-hybridization.     

Comparative morphology and morphometry of alveolar macrophages from six species

Pulmonary alveolar macrophages (PAM) were collected from normal, healthy mice, rats, dogs, cynomolgus monkeys, chimpanzees, and humans and evaluated for morphologic and morphometric characteristics. The PAM of mice, rats, and dogs were morphologically similar and had statistically similar frequency distributions for size. The cell size distribution for these three species was relatively homogeneous. The PAM of nonhuman primates and humans were morphologically heterogenous with sometimes prominent cytoplasmic vacuolation, irregular cell outlines, and increased numbers of multinucleated cells as compared to the PAM of rodents and dogs. The mean size of human PAM was statistically greater than that for all other species evaluated, including nonhuman primates. These data indicate that significant differences in PAM morphology and size exist among species.     

Effect of respiratory apparatus on respiration

A mouthpiece plus noseclip (MP + NC) is frequently used in performing measurements of breathing patterns. Although the effects the apparatus exerts on breathing patterns have been studied, the mechanism of the changes it causes remains unclear. The current study examines the effects on respiratory patterns of a standard (17-mm-diam) MP + NC during room air (RA) breathing and the administration of 2 and 4% CO2 in normal volunteers and in patients 2-4 days after abdominal operation. When compared with values obtained with a noninvasive canopy system, the MP + NC induced increases in minute ventilation (VE), tidal volume (VT), and mean inspiratory flow (VT/TI), but not frequency (f) or inspiratory duty cycle, during both RA and CO2 administration. The percentage increase in VE, VT, and VT/TI caused by the MP + NC decreased as the concentration of CO2 increased. During RA breathing, the application of noseclip alone resulted in a decrease in f and an increase in VT, but VE and VT/TI were unchanged. The changes were attenuated during the administration of 2 and 4% CO2. Reducing the diameter of the mouthpiece to 9 mm abolished the alterations in breathing pattern observed with the larger (17-mm) diameter MP.     

Endogenous inhibitors of 4'-[3H]chlorodiazepam (Ro 5-4864) binding to 'peripheral' sites for benzodiazepines

'Peripheral' binding sites for benzodiazepines are under neural or homonal control in the pineal gland, olfactory bulb, and kidney. These observations prompted a search for an endogenous substance which could modulate these sites under physiological conditions. Acidified methanol extracts from several tissues (e.g. stomach, kidney, lung) were found to inhibit the binding of [3H]Ro 5-4864 to 'peripheral' binding sites, but did not significantly affect the binding of [3H]diazepam to 'brain' benzodiazepine receptors. Fractionation of a crude extract prepared from antral stomach by either ultrafiltration or gel filtration chromatography yielded high (Mr greater than 10 000) and low (Mr less than 1000) Mr fractions which competitively inhibited [3H]Ro 5-4864 binding to 'peripheral' sites. These observations suggest the presence of endogenous substances in several rat tissues which may represent physiologically important ligands for 'peripheral' binding sites for benzodiazepines.     

Characterization of an anti-peptide antibody that recognizes the murine analogue of the human T cell antigen receptor-T3 delta-chain

The T cell antigen receptor consists of two disulfide-linked 40,000 to 45,000 dalton glycoproteins (alpha and beta) that contain variable and constant regions analogous to those found in immunoglobulin molecules. The antigen receptor on murine T cells is noncovalently associated with four additional nonpolymorphic structures. We describe an antibody that binds one of these molecules, a 26,000 dalton glycoprotein homologous to the human T3 delta-chain. This antibody immunoprecipitates the entire antigen receptor complex from a T cell hybridoma and from normal murine thymocytes. It represents the first reagent that can immunoprecipitate the antigen receptor complex on all murine T cells.     

Oxygen reduction in chloroplasts and the ascorbate cycle

Current views concerning the generation of superoxide radicals and hydrogen peroxide in chloroplasts as well as their toxic influences on photosynthesis are presented. Systems of H2O2 detoxification including the ascorbate peroxidase reactions and the ascorbate regenerating reactions are described. Data concerning mechanisms of monodehydroascorbate reduction by the photosynthetic electron transport chain are reviewed. The participation of the Mehler-peroxidase reaction in building of a proton gradient across the thylakoid membrane and its possible input in ATP synthesis and in protection from photoinhibition are analyzed. Ascorbate functions in chloroplasts and the need to consider the high concentration of ascorbate in chloroplasts when photosynthetic reactions in vivo are discussed are briefly reviewed.     

Evolution of normal and neoplastic tissue stem cells: progress after Robert Hooke

The appearance of stem cells coincides with the transition from single-celled organisms to metazoans. Stem cells are capable of self-renewal as well as differentiation. Each tissue is maintained by self-renewing tissue-specific stem cells. The accumulation of mutations that lead to preleukaemia are in the blood-forming stem cell, while the transition to leukaemia stem cells occurs in the clone at a progenitor stage. All leukaemia and cancer cells escape being removed by scavenger macrophages by expressing the ''don''t eat me'' signal CD47. Blocking antibodies to CD47 are therapeutics for all cancers, and are currently being tested in clinical trials in the US and UK.