The Georgia Centenarian Study.
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Adaptation, Physiological↗
Biomedical subjects
M A Johnson
Publications and source records attributed to M A Johnson.
Nutritional patterns of centenarians.
This study compares the dietary patterns of centenarians (n = 24) with elderly adults in their sixties (n = 54) and eighties (n = 47). Compared to the younger cohorts, centenarians consumed breakfast more regularly, avoided weight loss diets and large fluctuations in body weight, consumed slightly more vegetables, and relied on their doctor and family more than on the news media for nutrition information. On the other hand, centenarians were less likely to consume diets low in fat and to comply with nutritional guidelines designed to reduce the risk of chronic disease. Elderly black men consumed diets higher in sweets and fat compared to black women and white men and women. Nearly three times as many blacks expressed the desire to eat more nutritiously. High nutrition risks, particularly in blacks, were associated with lower physical and mental health and impaired activities of daily living.
Activities of Daily Living↗
Religiosity and adaptation in the oldest-old.
Previous research has yielded mixed results with respect to the relationship between religiosity and adaptation in older adults. Most studies show that religiosity is stable over the life span, but that religiosity may or may not be related to such factors as physical and mental health, life satisfaction, and coping. This study adds to earlier investigations by including centenarians among the sample. The preliminary results of this research project support earlier findings that religiosity does not change significantly as one ages, although there is a trend in the results that suggests otherwise. The results also indicate a significant relationship between religiosity and physical health but no significant relationship between religiosity and mental health and life satisfaction. Religiosity and coping are strongly related, and there is the suggestion that religious coping mechanisms might be more important in the oldest-old.
Adaptation, Psychological↗
The influences of cognitive resources on adaptation and old age.
In the Georgia Centenarian Study, cognitive resources were estimated by fluid and crystallized intelligence, acquisition and retrieval of new information, retrieval of familiar information, and problem-solving ability in community-dwelling and nondemented adults ranging from sixty to one hundred plus years of age. Five clusters of results were found: 1) cognitive performances were lower for the older cohorts; 2) when cognitive activities were dependent on everyday experiences, no age-related problem-solving decline was found; 3) physical health and mental health can significantly influence cognitive performances; 4) cognitive and personality factors can combine to account for a larger amount of adaptation variance than can be accounted for by either of the factors alone; and 5) individuals with a high level of intelligence and affect sustain their instrumental activities of daily living. Cognitive resources were an important contributor to successful adaptation for the oldest-old.
Activities of Daily Living↗
Alveolar macrophage populations are distorted in immunocompromised patients with pneumonitis.
Alveolar macrophages (AM) were obtained by bronchoalveolar lavage (BAL) from patients presenting with pneumonitis: 30 human immunodeficiency virus (HIV)-infected individuals and 12 transplant recipients. Nine normal volunteers acted as controls. The cells were washed and cytospins prepared. Monoclonal antibodies (MoAbs) and immunoperoxidase methods were used to analyse the expression of HLA-DR molecules as well as phenotypic macrophage markers. P values apply to the differences between medians using the Mann-Whitney test. Median percentages of macrophages, lymphocytes and neutrophils were similar in all three groups. No differences were found in the median percentages of macrophages expressing the monocyte phenotype (MoAb UCHM1, CD14). However, in HIV-infected patients and transplant recipients a median of only 45% of macrophages expressed the pan-macrophage phenotype identified by MoAb EBM11 (CD68) in contrast with 98% in the normal volunteers. The AM population expressing the dendritic cell marker (MoAb RFD1) was also markedly reduced in both groups of immunocompromised patients (2 vs 28% in normal volunteers). Transplant recipients had significantly more phagocytic cells identified by MoAb RFD7 than the HIV-infected patients (25 vs 2%), but the numbers were still low when compared with the volunteers (48%). HLA-DR expression on BAL cells was reduced by 90% in both immunocompromised groups. For the transplant recipients, severity of pneumonitis was correlated with expression of dendritic cell marker RFD1, (Spearman's rank correlation r = 0.538, p less than 0.05) and pan-macrophage marker EBM11 (r = 0.581, p less than 0.05), while no such correlation was found in HIV-infected patients. These results suggest that a defective macrophage population is probably a serious factor contributing to immunosuppression.
Adult↗
Open access clinic providing HIV-I antibody results on day of testing: the first twelve months.
OBJECTIVES: To determine the sociodemographic profile, risk category, and prevalence of HIV-I infection among people attending a clinic providing counselling, medical advice, and results of HIV-I antibody testing on the day of consultation; to determine the stage of infection and peripheral blood CD4 cell count among attenders with detectable HIV-I antibodies. DESIGN: Analysis of prospectively collected data for the 12 months from March 1989. SETTING: Same day testing clinic run by the HIV/AIDS team at an urban teaching hospital. PATIENTS: 561 consecutive people choosing to attend and proceeding to HIV-I testing. RESULTS: The demand for the service caused it to run to capacity within six months. The median age of those attending was 28 years and 65% (364 patients) were male. The overall prevalence of HIV-I infection was 3.9% (22 patients). The greatest prevalence was in men reporting their primary risk as homosexual contact (11.9%, 13/109). The median CD4 cell count in the 22 patients who had detectable HIV-I antibodies was 0.31 x 10(9) cells/l (normal range 0.5 x 10(9)/l to 1.2 x 10(9)/l). Twenty of these patients were asymptomatic (Centers for Disease Control stages II or III), 14 had CD4 cell counts below 0.5 x 10(9)/l. CONCLUSIONS: There is a recognisable demand for a service providing rapid results of HIV-I antibody testing in this setting. The overall seroprevalence of 3.9% is comparable with the 5.8% reported from freestanding clinics in the United States. Most patients with HIV-I antibodies detected in this way are asymptomatic but could benefit from early medical intervention because of low CD4 cell counts.
Acquired Immunodeficiency Syndrome↗
Pneumothorax and aerosolised pentamidine prophylaxis.
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Aerosols↗
Identification of a mutation in the promoter region of the dystrophin gene in a patient with atypical Becker muscular dystrophy.
We have identified 7 patients with Becker muscular dystrophy (BMD) in whom analysis of dystrophin by immunoblotting shows a full-sized molecule produced at reduced abundance compared with controls. They have no detectable deletion in their dystrophin cDNA. One patient presented atypically with unusually severe cramps as his only symptom for 25 years. These patients were investigated using the polymerase chain reaction (PCR) with 3 sets of primers within the promoter region of the dystrophin gene, followed by dot blot and restriction analysis. In the patient with the atypical history, one of the expected fragments on PCR failed to amplify. A large deletion was excluded by the finding of normally sized fragments on amplification with the other primer sets. The mutation was localised to the 3' end of the forward primer binding site by dot blot and restriction analysis. This result supports the hypothesis that, in patients with a full-sized dystrophin molecule produced at reduced abundance, the phenotype may result from a mutation in the promoter region of the dystrophin gene. The atypical history of the patient in whom this was detected adds to the variety of phenotypes now known to exist as BMD.
Adolescent↗
Gallid herpesvirus 1 (infectious laryngotracheitis virus): cloning and physical maps of the SA-2 strain.
Clones representing 90% of the genome of Gallid herpesvirus 1 (infectious laryngotracheitis virus; ILTV) were obtained and used in hybridization experiments to construct EcoRI, KpnI amd SmaI physical maps. The genome was 155 kilobase pairs (kbp) and comprised of a long unique sequence (120 kbp) and a short unique sequence (17 kbp) bounded by repeat sequences each of 9 kbp. An unrelated second pair of repeat sequences was located at 0.67 and 0.88 map untis. A terminal repeat of the unique long region (UL) was also detected, but no isomerization of UL was detected.
Animals↗
Nucleotide sequence of the gene encoding infectious laryngotracheitis virus glycoprotein B.
The nucleotide sequence of the infectious laryngotracheitis virus (ILTV) gene encoding the 205K complex glycoprotein (gp205) was determined. The gene is contained within a 3-kb EcoRI restriction fragment mapping at approximately map coordinates 0.23 to 0.25 in the UL region of the ILTV genome and is transcribed from right to left. Nucleotide sequence analysis of the DNA fragment identified a single, long open reading frame capable of encoding 873 amino acids. The predicted precursor polypeptide derived from this open reading frame would have a calculated Mr of 98,895 Da and contains nine potential glycosylation sites. Hydropathic analysis indicates the presence of an amino terminal hydrophobic sequence and hydrophobic carboxyl terminal domain which may function as a signal peptide and a membrane anchor sequence, respectively. Comparison of the predicted ILTV gp205 protein sequence with those of other herpesviruses revealed a significant sequence similarity with gB-like glycoproteins. Extensive homology was observed throughout the molecule except for the amino and carboxyl termini. The high homology in predicted primary and secondary structures is consistent with the essential role of the gB family of proteins for viral infectivity and pathogenesis.
Amino Acid Sequence↗
The effect of copper deficiency on adriamycin toxicity.
The effect of copper (Cu) deficiency on antioxidant status of liver and heart and its effect on adriamycin toxicity was assessed. Weanling rats were fed Cu-adequate (+Cu) and Cu-deficient (-Cu) diets for 3 weeks and then injected intraperitoneally once with saline or adriamycin (8 mg/kg). All -Cu rats had increased heart/body weight ratios compared to +Cu rats. Regardless of Cu status, adriamycin decreased body weight and increased heart cytochrome c oxidase, but had no effect on Cu,Zn-superoxide dismutase, glutathione peroxidase, the thiobarbituric acid (TBA) index or liver cytochrome c oxidase activity. -Cu, adriamycin rats had significantly decreased heart weights (0.54 + 0.02 g/kg body wt.) compared to -Cu, saline rats (0.69 +/- 0.05 g/kg body wt.). Four of 6 -Cu rats given adriamycin had abnormal EKGs, with 3 showing extrasystoles and 1 having a severe bradycardia. All +Cu rats given adriamycin had normal EKGs. Pathological changes detected with electron microscopy were most severe in -Cu rats given adriamycin.
Animals↗
New methods in the diagnosis and management of cerebral toxoplasmosis associated with the acquired immune deficiency syndrome.
Cerebral toxoplasmosis is a life-threatening condition associated with the acquired immune deficiency syndrome (AIDS). Current diagnostic and therapeutic methods have serious limitations. The diagnosis of cerebral toxoplasma infection in a patient with AIDS was assisted by the detection of specific IgM in a highly sensitive immunosorbent agglutination assay and by the demonstration of Toxoplasma gondii nucleic acid in a brain biopsy specimen by means of the polymerase chain reaction. Following initial failure of the patient to respond to treatment with sulphadiazine and pyrimethamine, clinical improvement was observed during treatment with clindamycin followed by dapsone. Further assessment of novel methods in the management of cerebral toxoplasmosis is required.
Acquired Immunodeficiency Syndrome↗
Iron supplementation increases gentamicin nephrotoxicity in rats.
Gentamicin (GM), an aminoglycoside antibiotic, can cause acute renal failure in humans and experimental animals. It has been proposed that lipid peroxidation may play a role in GM nephrotoxicity. Nutrients such as copper, selenium or iron that influence lipid peroxidation may also be a factor in toxicity. This study investigated the effect of supplemental dietary iron on the nephrotoxicity of GM. Weanling male Sprague-Dawley rats were fed control [0.75 mmol (42 mg) iron/kg] or iron-supplemented [4.32 mmol (242 mg) iron/kg] diets for 3 wk. Rats were subsequently injected intraperitoneally with GM (50 or 100 mg.kg body wt-1.d-1) or saline for 8 d. High dietary iron resulted in greater sensitivity to GM (100 mg/kg body wt) toxicity in terms of elevated urinary excretion of n-acetyl-beta-glucosaminidase (NAG) and increased mineralization, casts and megalocytes in renal tubules. After GM treatment was terminated, NAG excretion decreased with both dietary treatments. However, renal tubular cell damage, due to GM, remained higher than in saline-treated controls in rats fed 4.32 mmol iron/kg diet.
Acute Kidney Injury↗
Cholesterol ester deposition is reduced in rats with hypercholesterolemia and hypertension.
High K diets prevent hypertensive endothelial injury and intimal thickening. Cholesterol esters often deposit during hypercholesterolemia. We investigated whether a high K diet would influence cholesterol ester deposits in stroke prone SHR rats. Stroke prone SHR rats were fed for 3 months a basic diet containing 4% cholesterol, 14% coconut oil and 7% NaCl. One group of 13 rats had normal (.5%) K in the diet. Another group of 10 rats ate high (2.1%) K. Mean intra-arterial BPs averaged 165 mmHg in the normal K group and 161 mmHg in the high K group (NS). The serum cholesterol averaged 229 mg/dl in the normal K group and 214 in the high K group (NS). Total aortic cholesterol esters per rat averaged 187 micrograms in normal K vs 68 micrograms in high K, measured by gas chromatography. Thus high K reduced cholesterol ester deposits by 64% (p less than .0003), even though BPs and cholesterol levels were quite similar in the two groups. Both high cholesterol and high BP injure endothelial cells and increase invasion of monocytes and vascular smooth muscle cells into the intima and increase endothelial permeability to proteins. With high plasma cholesterol, these processes lead to atherosclerosis with cholesterol ester deposition. The high K diet, by protecting endothelial cells, can greatly decrease this cholesterol ester deposition. This effect could possibly be useful for preventing heart attacks in human hypertension.
Animals↗
Leukotriene C4 disposition and metabolism in the anesthetized and endotoxemic dog.
The metabolism and disposition of tritiated leukotriene C4, [3H]-LTC4, were studied in control dogs and endotoxin-treated dogs. Radioactivity was monitored in plasma, bile, and urine for 4.5 hr after an IV bolus of [3H]-LTC4. A decreased recovery of radioactivity in bile and urine was observed in the endotoxin-treated dogs. Cumulative [3H]-LTC4 metabolic patterns in bile and urine were determined by reverse-phase high-performance liquid chromatography (RP-HPLC) separation. Three primary metabolites, [3H]-LTD4, [3H]-LTE4, and a polar metabolite, (0.15-0.19)LT, accounted for most of the total bile radioactivity. The same primary metabolites were found for endotoxin-treated dogs and in similar relative amounts. [3H]-LTE4 and the polar metabolite (0.15-0.21)LT were the primary metabolites found in urine, but no N-acetyl LTE4 was found in bile or urine for either group. Plasma incubation of [3H]-LTC4 revealed heat-sensitive dipeptidase and glutamyl transpeptidase activity with significant production of [3H]-LTD4 and [3H]-LTE4 after 5- and 30-min incubation. Pharmacokinetic analysis using the two-compartment open model revealed an increased distribution phase rate constant (alpha) and distribution phase half-life [t1/2(alpha)], and decreased clearance (ClB), volume of distribution [Vd(ss) and Vd(area)] and elimination rate microconstant (Kel) of tritiated leukotrienes for endotoxin-treated dogs. This analysis along with the maintained higher plasma levels of tritiated leukotrienes, [3H]-LTs, in endotoxin-treated dogs suggests that endotoxin caused a decreased body clearance and less peripheral tissue penetration of [3H]-LTs. Collectively, these results indicate that the metabolism of LTC4 to LTD4 and LTE4, but not N-acetyl LTE4, in dogs was similar to that reported for man, pig, and monkey but dissimilar to rat. Endotoxin did not affect the types or relative amounts of metabolites found in bile or urine but appears to affect the disposition of [3H]-LTs by decreasing clearance and distribution.
Anesthesia↗
Procainamide inhibits DNA methyltransferase in a human T cell line.
Procainamide, a widely used antiarrythmic, causes DNA hypomethylation in the human T cell line Jurkat, but the mechanism is unknown. We report that procainamide inhibits the DNA methyltransferase catalyzed transfer of methyl groups from S-adenosylmethionine to DNA, but has no effect on other known regulators of DNA methylation. Our results suggest that procainamide could inhibit cellular DNA methylation by inhibiting DNA methyltransferase activity.
Animals↗
Very mild muscular dystrophy associated with the deletion of 46% of dystrophin.
Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD), a much milder form of the disease where the age of onset can sometimes be as late as the third or fourth decade of life, are caused by mutations in the same X-linked gene, a 14 kilobase (kb) transcript which is spread over more than 2 megabases of the human X chromosome. The corresponding protein, dystrophin, has a relative molecular mass of 400,000. Most mutations causing DMD and BMD are deletions and deletions associated with both phenotypes are observed throughout the gene sequence. This observation led to the suggestion that DMD patients possess deletions that disrupt the reading frame of the protein, whereas BMD patients have deletions that retain the translational reading frame and enable the muscle cells to produce altered dystrophin products. This theory is supported by immunoblotting studies, which show that DMD patients lack dystrophin in their muscle cells or that dystrophin is present at very low levels, whereas BMD patients produce a protein with reduced abundance or abnormal size. Here we describe a deletion of the dystrophin gene in a family segregating for very mild BMD, one member of which was still ambulant at age 61 years, which removes a central part of the dystrophin gene encompassing 5,106 base pairs of coding sequence, almost half the coding information. Immunological analysis of muscle from one of the patients demonstrates that this mutation results in the production of a truncated polypeptide localized correctly in the muscle cell. These results are particularly significant in the context of gene therapy which, if it is ever envisaged, would be facilitated by the replacement of the very large dystrophin gene with a more manipulatable mini-gene construct.
Blotting, Western↗
Absence of immunoreactive enzyme protein in short-chain acylcoenzyme A dehydrogenase deficiency.
Defects of short-chain acylcoenzyme A dehydrogenase (SCAD) may cause a severe metabolic illness in children or a lipid storage myopathy in adults. The childhood form is associated with low enzyme activity, but the synthesis of a normal-size enzyme protein in cultured skin fibroblasts. We report further biochemical studies on the original patient described with myopathic SCAD deficiency. We show an absence of enzyme protein in skeletal muscle, which both confirms the original diagnosis and suggests that the two forms of SCAD deficiency have a different molecular basis.
Electrophoresis, Polyacrylamide Gel↗