Physiological and chemical indicators for early and late stages of sepsis in conscious rats

Endotoxin shock is a major cause of death in patients with septicemia. Endotoxin induces nitric oxide (NO) production and causes tissue damage. In addition, the release of oxygen free radicals has also been observed in endotoxin shock and was found to be responsible for the occurrence of multiple organ failure. The purpose of the present study was to evaluate suitable indicators for early and late stages of endotoxin shock. The experiments were designed to induce endotoxin shock in conscious rats by means of anEscherichia coli lipopolysaccharide (LPS) injection. Arterial pressure (AP) and heart rate (HR) were continuously monitored for 72 h after LPS administration. The maximal decrease in AP and increase in HR and nitrate/nitrite level occurred at 9–12 h following LPS administration. The white blood cell (WBC) count had decreased at 3 h. Hydroxyl radical (methyl guanidine, MG) decreased rapidly after LPS administration. Plasma levels of blood urea nitrogen (BUN), creatinine (Cr), lactic dehydrogenase (LDH), creatine phosphokinase (CPK), and glutamic oxaloacetic transaminase increased before the rise of amylase. Our results suggest that changes in AP, HR, WBC, free radicals, and chemical substances (BUN, Cr) can possibly serve as approximate indicators for the early stage of endotoxin shock. Severe multiple organ damage may be caused by amylase release in the late stage of endotoxin shock.     

Lamp-1 is upregulated in human glioblastoma cell lines induced to undergo apoptosis

Lysosome-associated membrane protein (LAMP)-1, one of the major protein components of the lysosomal membrane, is upregulated in the human glioblastoma cell lines, U-373 MG and LN-Z308, which undergo cisplatin-induced apoptosis. These human brain tumor cell lines demonstrated apoptosis in response to cisplatin/nifedipine treatment. Both cell lines demonstrated an apoptotic response by more than one criterion. Apoptosis was demonstrated by DNA fragmentation techniques such as DNA laddering, ApopTag in situ labeling, and an ELISA-based method of detecting liberated oligosomes. These cells also had characteristic morphologic changes and upregulation of bax consistent with apoptosis. LAMP-1 expression at the protein and mRNA level was examined and found to increase with cisplatin/nifedipine treatment. LAMP-1 expression was examined using indirect immunofluorescent staining, Northern blot analysis and Western blot analysis. The finding of an augmentation of LAMP-1 in these cells induced to die is enigmatic. These findings raise the possibility of LAMP-1 involvement in the apoptotic process.     

Les génotypes responsables de mucoviscidose ou d’absence bilatérale des canaux déférents ABCD

Over the last decade, the genetic basis for CBAVD has been identified by its association with CFTR gene mutations, and CBAVD is now generally considered to be a mild or incomplete form of CF. In this review, the author summarizes the main results of compilation of CFTR gene analysis conducted in French laboratories for 3,923 patients with CF and 800 males with CABVD. The degree of clinical expression can be affected by several variables, including the molecular mechanisms by which the various CFTR mutations impair or disrupt the function of the CFTR chloride channel. Phenotypic expression of CFTR mutational genotypes varies from severe, progressive pulmonary disease with pancreatic insufficiency (CF-PI), to mild pulmonary disease with pancreatic sufficiency (PS) or singleorgan forms of “CFTR-opathies”. In CF, a total of 310 different CFTR mutations accounting for 94% of 7,846 CF alleles have generated almost 500 different genotypes, comprising 2 severe mutations in 88% of cases (CF-PI), one severe mutation in trans to a mild mutation in 11% (CF-PS), and 2 mild mutations in 1% of identified genotypes. In CBAVD, 137 mutations scattered over the whole gene were identified in 60% of 1,600 CBAVD alleles during the study. Among the 150 characterized mutational CFTR genotypes, compound heterozygosity was the rule, and the most frequent CBAVD combinations were ΔF508/5T (35%), ΔF508/other mutation (30%, including ΔF508/R117H-7T: 5,6%), and 5T/other mutation (17%). No combination of two severe mutations was found in CBAVD (0%); by contrast with the CF population, 88% of genotypes identified in CBAVD comprised a severe mutation in trans to a mild mutation, and 12% consisted of 2 mild mutations. A total of 22 genotypes were shared by both CF and CBAVD. The role of the 5T allele as a splicing variant with variable, incomplete disease penetrance in CBAVD is reviewed. Other haplotype backgrounds, such as the TG12 sequence and the M470V polymorphism, may influence CFTR splicing and/or function. This study confirms the high molecular heterogeneity of CFTR mutations in CBAVD and emphasizes the importance of extensive CFTR analysis in these patients. Longterm follow-up studies of CBAVD patients are necessary in order to predict the phenotypic consequences of numerous CFTR mutational genotypes.     

Etiology and modification of gait instability in older adults: a randomized controlled trial of exercise.

Increased gait instability is common in older adults, even in the absence of overt disease. The goal of the present study was to quantitatively investigate the factors that contribute to gait instability and its potential reversibility in functionally impaired older adults. We studied 67 older men and women with functional impairment before and after they participated in a randomized placebo-controlled, 6-mo multimodal exercise trial. We found that 1) gait instability is multifactorial; 2) stride time variability is strongly associated with functional status and performance-based measures of function that have previously been shown to predict significant clinical outcomes such as morbidity and nursing home admission; 3) neuropsychological status and health-related quality of life play important, independent roles in gait instability; and 4) improvement in physiological capacity is associated with reduced gait instability. Although the etiology of gait instability in older persons with mild-moderate functional impairment is multifactorial, interventions designed to reduce gait instability may be effective in bringing about a more consistent and more stable walking pattern.     

Muon disrupts AKT hydrogen bond network in cancer

A cancer microenvironment generates strong hydrogen bond network system by the positive feedback loops supporting cancer complexity and robustness. Such network functions through the AKT locus generating high entropic energy supporting cancer metastatic robustness. Charged lepton particle muon follows the rule of Bragg effect during a collision with hydrogen network in cancer cells. Muon beam dismantles hydrogen bond network in cancer by the muon-catalyzed fusion, leading to apoptosis of cancer cells. Muon induces cumulative energy appearance on the hydrogen bond network in a cancer cell with its fast decay to an electron and two neutrinos. Thus, muon beam, muonic atom, muon neutrino shower, and electrons simultaneously cause fast neutralization of the AKT hydrogen bond network by the conversion of hydrogen into deuterium or helium, inactivating the hydrogen bond networks and inducing failure of cancer complexity and robustness with the disappearance of a malignant phenotype.     

Identification of potentially critical genes in the development of heart failure after ST-segment elevation myocardial infarction (STEMI)

Heart failure (HF) remains a common complication after acute ST-segment elevation myocardial infarction (STEMI). Here, we aim to identify critical genes related to the developed HF in patients with STEMI using bioinformatics analysis. The microarray data of GSE59867, including peripheral blood samples from nine patients with post-infarct HF and eight patients without post-infarct HF, were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) between HF and non-HF groups were screened by LIMMA package. Functional enrichment analyses of DEGs were conducted, followed by construction of a protein-protein interaction (PPI) network. The dynamic messenger RNA (mRNA) level of the hub genes during the follow-up was analyzed to further elucidate their role in HF development. A total of 58 upregulated and 75 downregulated DEGs were screen out. They were mainly enriched in biological processes about inflammatory response, extracellular matrix organization, response to cAMP, immune response, and positive regulation of cytosolic calcium ion concentration. Pathway analysis revealed that the DEGs were also involved in hematopoietic cell lineage, pathways in cancer, and extracellular matrix-receptor interaction. In the PPI network consisting of 58 nodes and 72 interactions, CXCL8 (degree = 15), THBS1 (degree = 8), FOS (degree = 7), and ITGA2B (degree = 6) were identified as the hub genes. In the comparison of patients with and without post-infarct HF, the mRNA level of these hub genes were all higher within 30 days but reached similar at 6 months after STEMI. In conclusion, CXCL8, THBS1, FOS, and ITGA2B may play important roles in the development of HF after acute STEMI.     

Reviews

The Family Album. A film by Alan Berliner. 16mm, 55min, b/w. Distributed by Filmmakers Library, Inc.

Beyond Words—Images from America's Concentration Camps. By Deborah Gesensway and Mindy Roseman. 1987, 176 pages, illustrated. Ithaca: Cornell University Press. Price: cloth $24.95.

The Lau (Granada Television “Disappearing World” Series). A film by Leslie Woodhead, producer‐director; Jon Woods, camera; Ray French, sound; Kimball Horton, editor; David Wasson, researcher; and Pierre Maranda, anthropological consultant. 1987, video, color, 52 minutes. Dialogues: Lau. Subtitles: English. Narration: English. Distributed by Granada TV International, Suite 3468, 1221 Avenue of the Americas, New York, NY 10020, tele. 212–242–2363. Price: on application.

Men's Lives: The Surfmen and Baymen of the South Fork. By Peter Matthiessen. 1986, New York: Random House. Price: hardcover $29.95; softcover $7.95 (Vintage Press); limited edition $200 (University of Washington Press, Seattle).

In Her Own Time. A film by Lynne Littman with Barbara Myerhoff. 1986, 16mm, color, 60 minutes. Distributed by Direct Cinema, Ltd., P.O. Box 69589, Los Angeles, CA 90060, tele. 213–652–8000. Price: 16mm—purchase $895, rental $100; video—purchase $350, rental $50 (prices quoted are for educational institutions only).

The Miracle of Intervale Avenue. A film by Irving Rappaport, producer; Ken Howard, director; and Jack Kugelmaas, associate producer. 1983, 16mm, color, 65 minutes. Catalog #430. Distributed by Ergo Media, Inc., P.O. Box 2037, Teaneck, NJ 07666, tele. 201–692–0404.

Some Babies Die. A film by Martyn Landon Down. Australia, 16mm, color, 54 minutes. Distributed by The University of California Extension Media Center, 2176 Shattuck Avenue, Berkeley, CA 94704, tele. 415–642–1340. Price: 16mm—purchase $850, rental $60; video—purchase $450, rental $60.

El Sebou’: The Egyptian Birth Ritual. A film by Fadwa El Guindi; produced by El Nil Research Project; co‐sponsored by the Office of Folklife, Smithsonian Institution. 1986, 16mm, color, 27 minutes. Distributed by El Nil Research Project, 1157 Beverwil Drive, Los Angeles, CA 90035, tele. 213–553–5645. Price: 16mm—purchase $570, rental $70; video—purchase $370. Screenings: Society for Visual Anthropology (1987 Award for Excellence); 1987 Margaret Mead Film Festival; Royal Anthropological Institute (1988 Commendation).

The Making of El Sebou‘

Classified People. Yolande Zauberman, director; produced by OBSESSION/INA/CNC/ FR3‐TOULOUSE; Dewald Aukema, camera; Tony Bensusan, sound; Jean‐François Naudon, editor. 1987, 16mm, color, 53 minutes. Distributed by TELEMONDIS, 15, rue Mesnil, 75016, Paris, tele. 47–27–03–84, telex: 649 078 TELMOND. In U.S., distributed by Filmmaker's Library, 124 E. 40th Street, New York, NY 10016, tele. 212–355–6545. Price: 16mm—rental only $150; video (½″ or ¾″)—purchase $75, rental $75. Screenings: Festival of Women's Films at Créteil (Prix de Jury); Festival of Young Directors at Belfort (Prix de Publique); Bilan du Film Ethnographique 1988 (Prix Nanook/Grand Prix); 1988 Cinéma du Réel; 1987 Margaret Mead Film Festival; U.S. Public Television.

To Cross the Border: An interview with Filmmaker Yolande Zauberman, Paris, May 1988.