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Publications and source records attributed to C L Johnson.
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The synthesis of a series of novel analogues of lipid A, the active principle of lipopolysaccharide, is reported. In these compounds, the 1-O-phosphono and (R)-3-hydroxytetradecanoyl moieties of native Salmonella minnesota R595 lipid A have been replaced with hydrogen and the length of the normal fatty acyl residues has been systematically varied. Normal fatty acid chain length in the 3-O-desacyl monophosphoryl lipid A (MLA) series is shown to be a critical determinant of iNOS gene expression in activated mouse macrophages and the induction of proinflammatory cytokines in human peripheral monocytes. Examination of pyrogenicity in rabbits and lethal toxicity in D-galactosamine-treated mice shows that toxic effects in the MLA series can be ameliorated by modifying fatty acid chain length. When used as an adjuvant for tetanus toxoid vaccines, certain MLA derivatives enhance the production of tetanus toxoid-specific antibodies in mice.
BACKGROUND: The concentration of circulating total homocysteine is a sensitive marker of inadequate folate and vitamin B12 status. Elevated homocysteine concentrations are associated with an increased risk for vascular disease. OBJECTIVE: To identify reference ranges for serum total homocysteine concentration in U.S. residents and quantify the contribution of circulating vitamin concentrations to high homocysteine concentrations. DESIGN: Cross-sectional prevalence study. SETTING: United States. PATIENTS: A nationally representative sample of 3563 male participants and 4523 female participants 12 years of age or older who participated in the third National Health and Nutrition Examination Survey. MEASUREMENTS: Reference ranges (5th and 95th percentiles) for the total homocysteine concentration were defined among participants who were folate- and vitamin B12-replete and had normal creatinine concentrations. A high total homocysteine concentration was defined as one that exceeded the sex-specific 95th percentile for the reference sample (participants 20 to 39 years of age). The population attributable risk percentage was calculated to determine the contribution of low folate (<11 nmol/L) and vitamin B12 (<185 pmol/L) concentrations to a high homocysteine concentration. RESULTS: Reference ranges for serum total homocysteine concentration increased with age; these ranges were 4.3 to 9.9 micromol/L for male participants and 3.3 to 7.2 micromol/L for female participants 12 to 19 years of age and from 5.9 to 15.3 micromol/L for men and 4.9 to 11.6 micromol/L for women 60 years of age or older. A high homocysteine concentration was defined as at least 11.4 micromol/L for male participants and at least 10.4 micromol/L for female participants. Approximately two thirds of the cases of high homocysteine concentrations were associated with low vitamin concentrations. CONCLUSIONS: Upper reference limits for the serum total homocysteine concentration increased with age and were higher for male participants than for female participants at all ages. In most cases, high homocysteine concentrations were associated with low serum vitamin concentrations.
A novel series of acylated omega-aminoalkyl 2-amino-2-deoxy-4-phosphono-beta-D-glucopyranosides (aminoalkyl glucosaminide 4-phosphates) was synthesized and screened for immunostimulant activity. Several of these compounds enhance the production of tetanus toxoid-specific antibodies in mice and augment vaccine-induced cytotoxic T cells against EG.7-ova target cells.
The recommendations of the Fifth American College of Chest Physicians (ACCP) Consensus Conference on Antithrombotic Therapy are reviewed, with a focus on outpatient anticoagulation management in adults. Numerous therapeutic recommendations have changed since the Fourth ACCP Consensus Conference on Antithrombotic Therapy. The system of grading recommendations has been modified to emphasize clinically important differences and to take into account the benefit-risk ratio of each treatment option. The International Normalized Ratio (INR) goal is now expressed as a specific target value within a range rather than simply an INR range. The recommendations of the fifth conference cover initiation of warfarin therapy, hemorrhagic complications, management of excessive anticoagulation, interruption of warfarin therapy for patients requiring surgery, nonvalvular atrial fibrillation, cardioversion in patients with atrial fibrillation, valvular heart disease, mechanical and biological prosthetic heart valves, coronary artery disease, saphenous vein and internal mammary artery bypass grafts, peripheral arterial occlusive disease, prevention of venous thromboembolism, treatment of venous thromboembolism, stroke prevention in patients with cerebrovascular disease, and pregnancy. Since the fourth consensus conference, new anticoagulation therapies and indications have emerged; the recommendations of the Fifth ACCP Consensus Conference on Antithrombotic Therapy have provided practitioners with a resource of immense value.
BACKGROUND: The elevation of circulating total homocysteine concentrations in a fasting state is associated with an increased risk of occlusive vascular disease. OBJECTIVE: The primary goals of this study were to describe the distribution of serum total homocysteine concentrations in the United States and to test for differences in homocysteine concentrations among sex, age, and race-ethnicity categories. DESIGN: Using surplus sera from phase 2 of the third National Health and Nutrition Examination Survey, we measured serum total homocysteine concentrations for a nationally representative sample of 3766 males and 4819 females aged > or = 12 y. RESULTS: Age-adjusted geometric mean total homocysteine concentrations were 9.6 and 7.9 mmol/L in non-Hispanic white males and females, 9.8 and 8.2 mmol/L in non-Hispanic black males and females, and 9.4 and 7.4 mmol/L in Mexican American males and females, respectively. Age-adjusted geometric mean total homocysteine concentrations were significantly lower in females than in males in each race-ethnicity group (P < 0.01) and were significantly lower in Mexican American females than in non-Hispanic white and non-Hispanic black females (P < 0.01). There was a significant age-sex interaction (P < 0.01), reflecting the fact that homocysteine concentrations in females tended to diverge from those in males at younger ages and converge with those in males at older ages. CONCLUSIONS: The first data on homocysteine concentrations in a nationally representative sample of Americans confirm the age and sex differences reported previously in nonrepresentative samples. These data also indicate that differences between Mexican American and non-Hispanic females may influence circulating homocysteine concentrations.
OBJECTIVES: The purpose here is to identify those processes that account for the more active and supportive kinship networks among Black oldest old than found among their White age peers. METHODS: Focused interviews were conducted with 122 Blacks 85 years and older. Both open-ended and semistructured questions were asked in order to determine how Blacks defined family and kinship membership, their expectations for kin, and the desired levels of reciprocity. FINDINGS: A content analysis of the responses indicated that Blacks defined the boundaries of their families flexibly so as to include fictive kin, and they upgraded more distant kin into the status of primary kin. They also emphasized the importance of collateral relatives so as to expand the size of the network. DISCUSSION: These processes use personal choices as well as immediate needs to expand the basis of relatedness beyond blood and marriage. Thus the supportive capacities of networks increase in order to serve a potentially vulnerable population.
OBJECTIVE: This paper evaluates the possibility that examiner bias or other factors contributed to an observed decline in pocket depth and gingivitis between the two three-year sequential periods of time (or phases) covered by the Third National Health and Nutrition Examination Survey (NHANES III). METHODS: Prevalences of periodontal conditions were analyzed using data from two sets of repeat oral health examinations by examining dentists of NHANES III sample persons. The first set includes sample persons who were examined twice by the same examining dentist at an interval of one to six weeks. The second set includes sample persons who were assessed on the same day by both an examining dentist and a reference dentist. Other possible sources of error also were evaluated. RESULTS: Overall kappa statistics measuring agreement between or within dental examiners were within the range observed for other periodontal disease surveys. While differences were found among dentists in the prevalence of pocket depth of 4 mm or more, for each group of sample persons assessed by a reference examiner-examining dentist pair, the reference examiner's periodontal measurements closely corresponded to measurements made by the examining dentists. CONCLUSIONS: Differences between dental examiners in prevalences of periodontal conditions may be due in part to the fact that examinees were not randomly assigned to examiners. As a result, the sample persons examined by each dentist may not have been alike in characteristics thought to affect periodontal disease status. These findings suggest that the observed declines in periodontal health status between phases is not due to examiner bias. This unexplained decline may be the result of sampling variation. It is recommended that combined six-year survey results be presented whenever possible.
Five patients from a single institution received concomitant warfarin and 5-fluorouracil (5-FU) during a 3-year period. The mean weekly warfarin dose before starting chemotherapy was 40.66 mg and during chemotherapy it was 24 mg (p=0.0026). All patients required a warfarin dosage reduction (range 18-74%, mean 44%). Two patients were hospitalized, one with a major retroperitoneal bleed, the other for fresh-frozen plasma administration and observation. Maximum international normalized ratios (INRs) ranged from 3.66-23.7. This series confirms a common, clinically significant interaction between warfarin and 5-FU. An interaction between capecitabine, the orally available prodrug of 5-FU, and warfarin also has been reported. We recommend weekly monitoring of prothrombin time and INR for all patients receiving concomitant warfarin and 5-FU or capecitabine.
Elevations from the Mars Orbiter Laser Altimeter (MOLA) have been used to construct a precise topographic map of the martian north polar region. The northern ice cap has a maximum elevation of 3 kilometers above its surroundings but lies within a 5-kilometer-deep hemispheric depression that is contiguous with the area into which most outflow channels emptied. Polar cap topography displays evidence of modification by ablation, flow, and wind and is consistent with a primarily H2O composition. Correlation of topography with images suggests that the cap was more spatially extensive in the past. The cap volume of 1.2 x 10(6) to 1.7 x 10(6) cubic kilometers is about half that of the Greenland ice cap. Clouds observed over the polar cap are likely composed of CO2 that condensed out of the atmosphere during northern hemisphere winter. Many clouds exhibit dynamical structure likely caused by the interaction of propagating wave fronts with surface topography.
BACKGROUND: A population-based hemochromatosis screening program that uses serum transferrin saturation has been proposed, but few data exist on the number of U.S. adults that such a program would identify for further testing. OBJECTIVE: To determine the prevalence of an initially elevated serum transferrin saturation and the prevalence of concurrently elevated serum transferrin saturation and serum ferritin levels in the adult population of the United States. DESIGN: Nationally representative cross-sectional survey of the noninstitutionalized U.S. civilian population. PARTICIPANTS: 15 839 men and nonpregnant women 20 years of age and older who were examined in the third National Health and Nutrition Examination Survey (1988-1994). MEASUREMENTS: Single measurements of serum transferrin saturations and serum ferritin levels. Cut-off values used to define elevated serum transferrin saturation ranged from greater than 45% to greater than 62%. RESULTS: The prevalence of initially elevated serum transferrin saturation ranged from 1% to 6%. Approximately 11% to 22% of those with elevated serum transferrin saturation had concurrently elevated serum ferritin levels. The prevalence of elevated serum transferrin saturation was lower in women than in men when the same cut-off value was used to define elevated serum transferrin saturation. The prevalence of elevated serum transferrin saturation in non-Hispanic black persons and Mexican-Americans was similar to or slightly less than that in non-Hispanic white persons. The prevalence of elevated serum transferrin saturation in persons 20 to 49 years of age was as high as or higher than that in older adults. CONCLUSIONS: A hemochromatosis screening program that uses a cut-off value of greater than 60% to define elevated serum transferrin saturation would identify an estimated 1.4 to 2.5 million U.S. adults for further testing.
The clinical findings of eight families with Stickler syndrome were analyzed and compared with the results of linkage studies using a marker for the type II collagen gene (COL2A1). In six families, there was linkage of the phenotype to COL2A1. The manifestations of the affected individuals were similar to those of the original Stickler syndrome family [Stickler et al., Mayo. Clin. Proc. 40:433-455, 1965] and resembled the phenotype of the previously reported individuals or families with Stickler syndrome in which a dominant mutation in the COL2A1 gene has been identified. Linkage to COL2A1 was excluded in the two remaining families. The most striking difference between these two types of families was the absence of severe myopia and retinal detachment in the two unliked families. In the COL2A1 unlinked families, linkage of the phenotype to genes (COL11A1 and COL11A2) that encode pro alpha chains of type XI collagen, a minor cartilage-specific collagen, was also excluded. Since Stickler syndrome can be produced by mutations in COL2A1, COL11A1, and COL11A2, our data suggest that there is at least a fourth locus for Stickler syndrome.
OBJECTIVE: To develop new, nationally representative equations to predict stature for racial/ethnic groups of the elderly population in the United States. DESIGN: Anthropometric data for stature, knee height, and sitting height for adults aged 60 years or older were collected from a sample of persons in the third National Health and Nutrition Examination Survey (1988-1994), a national probability sample of the US population. SUBJECTS: A gender- and racial/ethnic-stratified sample of 4,750 persons from the US population (1,369 non-Hispanic white men, 1,472 non-Hispanic white women, 474 non-Hispanic black men, 481 non-Hispanic black women, 497 Mexican-American men, 457 Mexican-American women) aged 60 years or older participated in this study. STATISTICAL ANALYSES: Sampling weights were used to adjust the individual data to account for unequal probabilities of selection, nonresponse, and coverage errors so that all individual data used in these analyses represented national probability estimates. Regression analysis was performed to predict stature in each gender and ethnic group, and the results were cross-validated. RESULTS: Stature prediction models using knee height and age and sitting height and age were evaluated for each gender and racial/ethnic group. The equations with knee height and age were selected on the basis of root mean square error and pure errors in cross-validation and on the accuracy and validity of measures of knee height over sitting height. Results of these regressions, including regression coefficients, standard errors of the coefficients, multiple correlation coefficients, root mean square error, and the standard error for the individual for the final equations, are presented. CONCLUSIONS: New stature prediction equations using knee height and age are presented for non-Hispanic white, non-Hispanic black and Mexican-American elderly persons from current nationally representative data. These equations should be applied when a measure of stature cannot be obtained, for example, for persons with amputations of the leg, or with spinal curvature or who are confined to bed. Predicted stature values are acceptable surrogates in nutritional indexes.
OBJECTIVE: To describe the prevalence of, and trends in, overweight and obesity in the US population using standardized international definitions. DESIGN: Successive cross-sectional nationally representative surveys, including the National Health Examination Survey (NHES I; 1960-62) and the National Health and Nutrition Examination Surveys (NHANES I: 1971-1974; NHANES II: 1976-1980; NHANES III: 1988-94). Body mass index (BMI:kg/m2) was calculated from measured weight and height. Overweight and obesity were defined as follows: Overweight (BMI > or = 25.0); pre-obese (BMI 25.0-29.9), class I obesity (BMI 30.0-34.9), class II obesity (BMI 35.0-39.9), and class III obesity (BMI > or = 40.0). RESULTS: For men and women aged 20-74 y, the age-adjusted prevalence of BMI 25.0-29.9 showed little or no increase over time (NHES I: 30.5%, NHANES I: 32.0%, NHANES II: 31.5% and NHANES III: 32.0%) but the prevalence of obesity (BMI > or = 30.0) showed a large increase between NHANES II and NHANES III (NHES I: 12.8%; NHANES I, 14.1%; NHANES II, 14.5% and NHANES III, 22.5%). Trends were generally similar for all age, gender and race-ethnic groups. The crude prevalence of overweight and obesity (BMI >> 25.0) for age > or = 20 y was 59.4% for men, 50.7% for women and 54.9% overall. The prevalence of class III obesity (BMI > or = 40.0) exceeded 10% for non-Hispanic black women aged 40-59 y. CONCLUSIONS: Between 1976-80 and 1988-94, the prevalence of obesity (BMI > or= 30.0) increased markedly in the US. These findings are in agreement with trends seen elsewhere in the world. Use of standardized definitions facilitates international comparisons.
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OBJECTIVE: To determine the 1H MRS findings in patients with intractable temporal lobe epilepsy (TLE) who had no detectable abnormality on either qualitative or quantitative MRI. BACKGROUND: Previous work has indicated that approximately 20% of patients with TLE remain MRI negative after extensive qualitative and quantitative investigation. Single-voxel 1H MRS provides a means of identifying potentially diffuse disease. METHODS: Seven patients with intractable TLE, normal routine MRI, normal hippocampal volumes, and normal hippocampal and amygdala quantitative T2 values underwent single-voxel 1H MRS of the medial temporal lobes. The results are compared with those from 13 control subjects and 15 patients with evidence of hippocampal sclerosis (HS). RESULTS: The ratio N-acetylaspartate/(choline-creatine + phosphocreatine) was abnormally low in five of the seven MRI-negative patients. In two of these patients, the ratios were low bilaterally. The observed MRS ratios in the MRI-negative group with abnormal EEG were similar to those from temporal lobes ipsilateral to HS, suggesting the presence of widespread or diffuse disease of a similar degree in both groups. CONCLUSIONS: These results demonstrate that MRS can provide evidence of temporal lobe abnormalities in TLE patients who show no abnormality on extensive MRI investigation.
OBJECTIVES: This report presents national estimates of serum and red blood cell (RBC) folate and serum vitamin B12 distributions for persons 4 years and over, by sociodemographic variables. METHODS: The third National Health and Nutrition Examination Survey (NHANES III) (1988-94), provides information on the health and nutritional status of the civilian noninstitutionalized U.S. population. The analytic sample included 23,378 participants with serum folate data, 23,082 with RBC folate data, and 11,851 with serum vitamin B12 data. RESULTS: The mean serum and RBC folate concentrations are 7.2 and 196 nanograms per milliliter (ng/mL), respectively, and the mean serum vitamin B12 concentration is 518 picograms per milliliter (pg/mL). Non-Hispanic white people have higher mean serum and RBC folate concentrations than non-Hispanic black or Mexican American people. Serum vitamin B12 concentrations are lowest for older adults, and non-Hispanic black people have higher serum B12 concentrations than non-Hispanic white individuals. Only approximately 3 percent of the population has a serum B12 concentration less than 200 pg/mL. CONCLUSIONS: Inadequate folate status may be more prevalent among non-Hispanic black and Mexican American people. Data also suggest a modest prevalence of low serum B12 concentrations. Future assessments of folate and vitamin B12 status will be important to evaluate the impact of a recently enacted fortification policy.
OBJECTIVE: To determine the prevalence of iron deficiency and iron deficiency anemia in the US population. DESIGN: Nationally representative cross-sectional health examination survey that included venous blood measurements of iron status. MAIN OUTCOME MEASURES: Iron deficiency, defined as having an abnormal value for at least 2 of 3 laboratory tests of iron status (erythrocyte protoporphyrin, transferrin saturation, or serum ferritin); and iron deficiency anemia, defined as iron deficiency plus low hemoglobin. PARTICIPANTS: A total of 24,894 persons aged 1 year and older examined in the third National Health and Nutrition Examination Survey (1988-1994). RESULTS: Nine percent of toddlers aged 1 to 2 years and 9% to 11% of adolescent girls and women of childbearing age were iron deficient; of these, iron deficiency anemia was found in 3% and 2% to 5%, respectively. These prevalences correspond to approximately 700,000 toddlers and 7.8 million women with iron deficiency; of these, approximately 240,000 toddlers and 3.3 million women have iron deficiency anemia. Iron deficiency occurred in no more than 7% of older children or those older than 50 years, and in no more than 1% of teenage boys and young men. Among women of childbearing age, iron deficiency was more likely in those who are minority, low income, and multiparous. CONCLUSION: Iron deficiency and iron deficiency anemia are still relatively common in toddlers, adolescent girls, and women of childbearing age.