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1.
BMC Geriatr ; 21(1): 415, 2021 07 06.
Article in English | MEDLINE | ID: mdl-34229623

ABSTRACT

BACKGROUND: Older age and comorbid burden are both associated with adverse outcomes in SARS-CoV-2, but it is not known whether the association between comorbid burden and adverse outcomes differs in older and younger adults. OBJECTIVE: To compare the relationship between comorbid burden and adverse outcomes in adults with SARS-CoV-2 of different ages (18-64, 65-79 and ≥ 80 years). DESIGN, SETTING, AND PARTICIPANTS: Observational longitudinal cohort study of 170,528 patients who tested positive for SARS-CoV-2 in the US Department of Veterans Affairs (VA) Health Care System between 2/28/20 and 12/31/2020 who were followed through 01/31/2021. MEASUREMENTS: Charlson Comorbidity Index (CCI); Incidence of hospitalization, intensive care unit (ICU) admission, mechanical ventilation, and death within 30 days of a positive SARS-CoV-2 test. RESULTS: The cumulative 30-day incidence of death was 0.8% in cohort members < 65 years, 7.1% in those aged 65-79 years and 20.6% in those aged ≥80 years. The respective 30-day incidences of hospitalization were 8.2, 21.7 and 29.5%, of ICU admission were 2.7, 8.6, and 11% and of mechanical ventilation were 1, 3.9 and 3.2%. Median CCI (interquartile range) ranged from 0.0 (0.0, 2.0) in the youngest, to 4 (2.0, 7.0) in the oldest age group. The adjusted association of CCI with all outcomes was attenuated at older ages such that the threshold level of CCI above which the risk for each outcome exceeded the reference group (1st quartile) was lower in younger than in older cohort members (p < 0.001 for all age group interactions). LIMITATIONS: The CCI is calculated based on diagnostic codes, which may not provide an accurate assessment of comorbid burden. CONCLUSIONS: Age differences in the distribution and prognostic significance of overall comorbid burden could inform clinical management, vaccination prioritization and population health during the pandemic and argue for more work to understand the role of age and comorbidity in shaping the care of hospitalized patients with SARS-CoV-2.


Subject(s)
COVID-19 , SARS-CoV-2 , Aged , Hospitalization , Humans , Intensive Care Units , Longitudinal Studies , Middle Aged , Pandemics
2.
Eur Respir J ; 32(4): 938-44, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18550614

ABSTRACT

Exacerbations of chronic obstructive pulmonary disease (COPD) reduce quality of life and increase mortality. Genetic variation might explain the substantial variability seen in exacerbation frequency among COPD subjects with similar lung function. Polymorphisms in five candidate genes, previously associated with COPD susceptibility, were analysed in order to determine whether they demonstrated association with COPD exacerbations. A total of 88 single nucleotide polymorphisms (SNPs) in the genes microsomal epoxide hydrolase (EPHX1), transforming growth factor, beta-1 (TGFB1), serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 2 (SERPINE2), glutathione S-transferase pi (GSTP1) and surfactant protein B (SFTPB) were genotyped in 389 non-Hispanic white participants in the National Emphysema Treatment Trial. Exacerbations were defined as COPD-related emergency room visits or hospitalisations using the Centers for Medicare and Medicaid Services claims data. One or more exacerbations were experienced by 216 (56%) subjects during the study period. An SFTPB promoter polymorphism, rs3024791, was associated with COPD exacerbations. Logistic regression models, analysing a binary outcome of presence or absence of exacerbations, confirmed the association of rs3024791 with COPD exacerbations. Negative binomial regression models demonstrated association of multiple SFTPB SNPs (rs2118177, rs2304566, rs1130866 and rs3024791) with exacerbation rates. Polymorphisms in EPHX1, GSTP1, TGFB1 and SERPINE2 did not demonstrate association with COPD exacerbations. In conclusion, genetic variation in surfactant protein B is associated with chronic obstructive pulmonary disease susceptibility and exacerbation frequency.


Subject(s)
Polymorphism, Genetic , Pulmonary Disease, Chronic Obstructive/genetics , Pulmonary Surfactant-Associated Protein B/genetics , Aged , Alleles , Female , Genetic Predisposition to Disease , Genetic Variation , Genotype , Humans , Male , Middle Aged , Polymorphism, Single Nucleotide , Regression Analysis , Smoking
4.
J Bacteriol ; 144(3): 957-66, 1980 Dec.
Article in English | MEDLINE | ID: mdl-6777372

ABSTRACT

Cell walls from bacillus subtilis 168 were prepared by conventional methods and found to contain deoxyribonucleic acid (DNA). In transformation assays, after autolysis, it was found that two major regions of the chromosome were selectively enriched in the wall preparations. One region clustered around the replication origin and is represented by the markers purA16, ts8132, thiC5, sacA321, and hisA1. The other region included the replication terminus with representative loci metB10, citK5, gltA292, and pyrA1. All other (internal) loci which were examined showed no statistical enrichment. The two areas of enrichment were similar to but more extensive than those reported for membrane-DNA complexes. The wall preparations also contained protein and lipid, indicating a possible membrane involvement. Analyses of the cell walls revealed that the fatty acid composition of the membrane component was not typical of the for B. subtilis protoplast membranes or for lipoteichoic acids. In addition, radioiodination of cell wall autolysates, followed by gel electrophoresis and autoradiography, demonstrated the presence of proteins not readily detectable in bulk protoplast membranes or on the surfaces of intact cells. These data suggest that a unique component of the membrane and regions of the B. subtilis genome involved in DNA replication events are tightly associated with cell walls. The binding of DNA-membrane complexes to the "rigid" cell wall and the replication of the wall could be a mechanism by which the segregation of growing chromosomes occurs.


Subject(s)
Bacillus subtilis/genetics , Cell Wall/metabolism , DNA, Bacterial/metabolism , Transformation, Bacterial , Bacillus subtilis/metabolism , Bacillus subtilis/ultrastructure , Bacterial Proteins/analysis , DNA Replication , Fatty Acids/analysis , Genetic Markers
6.
Biochim Biophys Acta ; 551(1): 67-73, 1979 Feb 20.
Article in English | MEDLINE | ID: mdl-427154

ABSTRACT

HEp-2 cell monolayers were treated with 40% polyethylene glycol for 5 min which resulted in fusion during the subsequent incubation period. A loss of cell membrane components was detected in the polyethylene glycol-treated as well as phosphate buffer/saline-treated control cells, however the polyethylene glycol-treated cells released nearly twice the amount of [14C]acetate-labeled material and [3H]glycerol-labeled lipids into culture fluids than the control cells. It was further detected that the polyethylene glycol-treated cells released only approximately half the amount of protein, glycoprotein, and glycolipid as the control cells. These results suggest that polyethylene glycol exerts a differential mode of action against cell surface components and causes the treated cells to release membrane components rich in lipids but relatively low in protein and carbohydrate-containing components.


Subject(s)
Cell Membrane/ultrastructure , Liver Neoplasms, Experimental/ultrastructure , Polyethylene Glycols/pharmacology , Animals , Cell Line , Cell Membrane/drug effects , Glycoproteins/analysis , Kinetics , Membrane Lipids/analysis , Membrane Proteins/analysis , Phospholipids/analysis , Rats
7.
J Bacteriol ; 129(1): 547-9, 1977 Jan.
Article in English | MEDLINE | ID: mdl-401503

ABSTRACT

The cell wall of Bacillus subtilis 168 contains protein that is refractory to removal by salts, detergents, and denaturants.


Subject(s)
Bacillus subtilis/ultrastructure , Bacterial Proteins/metabolism , Bacillus subtilis/metabolism , Cell Wall/metabolism
8.
Br J Surg ; 62(4): 309-12, 1975 Apr.
Article in English | MEDLINE | ID: mdl-1131510

ABSTRACT

Six patients with watery postvagotomy diarrhoea and 4 patients with intractable diabetic diarrhoea were treated with cholestyramine. The diarrhoea responded completely to therapy, during which the stool content of water, sodium, postassium and magnesium fell. Two of the patients, while receiving cholestyramine, had a rise in faecal fat, but this was not accompanied by diarrhoea, the stools being well formed. Evidence is presented which suggests that the mechanism of diarrhoea is similar in both disorders and is due to division or neuropathy of the hepatic fibres of the vagus nerve. This results is distension of the gallbladder, contraction of which expels increased quantities of bile salts, which swamp the reabsorptive capacity of the small intestine and induce diarrhoea by direct action on the colon. If this theory is valid, cholecystectomy, by preventing large quantities of concentrated bile salts from suddenly entering the gut, may result in improvement of postvagotomy and diabetic diarrhoea.


Subject(s)
Diarrhea/etiology , Vagotomy/adverse effects , Adult , Bile/metabolism , Bile Acids and Salts/metabolism , Cholestyramine Resin/therapeutic use , Diabetes Complications , Diarrhea/drug therapy , Feces/analysis , Gallbladder/metabolism , Humans , Liver/innervation , Magnesium/analysis , Male , Middle Aged , Potassium/analysis , Sodium/analysis
9.
Proc Soc Exp Biol Med ; 148(2): 351-7, 1975 Feb.
Article in English | MEDLINE | ID: mdl-804699

ABSTRACT

The biosynthesis of phospho-lipids and neutral lipids in normal and monkey kidney cells infected with lymphogranuloma venereum were compared using 14C-acetate and 14-C-serine in pulse-chase experiments. Synthesis of phospholipids and nutral glycerolipids were inhibited in infected cells. Phosphatidyl ethanolamine (PE) synthesis increased while phosphatidyl choline, phosphatidyl serine and cardiolipin synthesis decreased in infected cells within 36 hr after infection. Sphingomyelin syntheisis decreased after 48 hr of infection. The synthesis of PE in the infected cell followed a similar pathway found in bacteria and could be distinguished from the normal host cell. An explanation of the parsitic requirement for lipid precursors has been proposed.


Subject(s)
Chlamydia , Lipids/biosynthesis , Lymphogranuloma Venereum , Phospholipids/biosynthesis , Acetates/metabolism , Animals , Cardiolipins/biosynthesis , Cells, Cultured , Diglycerides/biosynthesis , Fatty Acids/biosynthesis , Haplorhini , Kidney/metabolism , Phosphatidylcholines/biosynthesis , Phosphatidylethanolamines/biosynthesis , Phosphatidylserines/biosynthesis , Serine/metabolism , Sphingomyelins/biosynthesis , Triglycerides/biosynthesis
10.
Infect Immun ; 10(3): 464-70, 1974 Sep.
Article in English | MEDLINE | ID: mdl-4214771

ABSTRACT

Lipid metabolism of monkey kidney (LLC-MK-2) cells and cells infected with a Chlamydia trachomatis strain lymphogranuloma venereum (LGV) was studied. The protein-to-lipid ratio of normal MK-2 cells was found to increase linearly over a 60-h period of incubation. The protein-to-lipid ratio of the infected cells was similar to that in normal cells until 36 h after infection, when a plateau in the ratio was observed. Lipid synthesis of the infected cells was found to be inhibited after 48 h of infection. Turnover of host lipids did not appear to be markedly altered by infection with LGV over a 48-h period of incubation. An anteiso branched chain of 15:0 fatty acid was found in infected cells but not in normal cells. The appearance of this fatty acid, correlated with a rise in the infectivity of LGV, suggests that synthesis of specific lipids was associated with the infection.


Subject(s)
Granuloma Inguinale/metabolism , Kidney/metabolism , Lipid Metabolism , Acetates/metabolism , Animals , Carbon Radioisotopes , Cell Line , Chlamydia/isolation & purification , Culture Media , Culture Techniques , Esters , Fatty Acids/analysis , Fatty Alcohols , Granuloma Inguinale/microbiology , Haplorhini , Lipids/isolation & purification , Proteins/analysis , Viral Plaque Assay , Virus Cultivation
11.
J Bacteriol ; 104(1): 608-9, 1970 Oct.
Article in English | MEDLINE | ID: mdl-5473914

ABSTRACT

A difference in glycogen metabolism between two strains of Chlamydia agents was observed which can serve as a taxonomic marker to distinguish C. psittaci from C. trachomatis.


Subject(s)
Chlamydia , Glycogen/metabolism , HeLa Cells/metabolism , Carbon Isotopes , Chlamydia/classification , Glucose/metabolism
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