Study of proinflammatory responses induced by Yersinia pestis in human monocytes using cDNA arrays.

Yersinia pestis, the causative agent of plague, is known to develop strategies to overcome the host immune mechanisms and survive in the host. The molecular changes induced by Y. pestis in the host are not well delineated. Here, we examined the early events triggered after the intracellular infection of Y. pestis in human monocytes and lymphocytes by analyzing the host transcriptional profiles using cDNA arrays. We found that sets of genes that, especially at early time periods, were highly upregulated in monocytes alone when compared with a mixed culture of lymphocytes and monocytes. Gene expression responses revealed genes coding for cytokines, chemokines, transcription factors, inflammatory and apoptosis-related genes. Protein levels were measured, and real-time polymerase chain reaction was used to validate the microarray results. Our data suggest that intracellular infection of human monocytes with Y. pestis results in a strong inflammatory response at early time periods and a downregulation of genes such as thromobomodulin, which may play a role in coagulation, resulting in disseminated intravascular coagulation, a primary cause of death in plague infected hosts. We provide evidence that genomic analysis can provide a solid foundation to mechanistic insights to explain some of the symptoms induced by Y. pestis.

Sodium sensitivity in young adults with high resting end-tidal CO2.

BACKGROUND: Previous research with normotensive adults aged over 40 years ('older') found that sensitivity of blood pressure of subjects with high resting end-tidal partial pressures of CO2 to high sodium intake was greater than normal. OBJECTIVE: To test the hypothesis that the lesser sensitivity of blood pressure of young normotensive adults to high sodium intake is also a function of resting end-tidal partial pressure of CO2. DESIGN: Forty-eight Caucasian men and women (age 28.5 +/- 1.4 years) had a lower than normal dietary intake of sodium chloride for 4 days, and then ingested sodium chloride capsules for 7 days (an additional 190 mmol/day sodium chloride). Resting end-tidal partial pressure of CO2 and blood pressure, and 24 h ambulatory blood pressure, were measured before and after the high-sodium diet. Overnight urine samples were collected before and after the high-sodium diet to determine dietary compliance, and to assess changes in urinary excretion of endogenous digitalis-like factors (a ouabain-like factor, and a marinobufagenin-like factor) that covary with plasma volume. RESULTS: Subjects with high end-tidal partial pressures of CO2 had lower resting heart rates and lower urinary excretion of ouabain-like factor before sodium loading. Sodium loading decreased mean partial pressure of CO2 (by 0.8 +/- 0.2 mmHg) and increased only ambulatory systolic blood pressure (by 2.1 +/- 0.8 mmHg) for the whole group. However, the changes in resting systolic (r = 0.32, P < 0.025) and diastolic (r = 0.36, P < 0.01) blood pressures and in 24 h systolic (r = 0.28, P < 0.05) blood pressure after sodium loading were all positive functions of individual resting end-tidal partial pressures of CO2. Sodium loading increased urinary excretion of marinobufagenin-like factor (by 1.78 +/- 0.88 nmol) and the magnitude of the individual increase was a function of end-tidal partial pressure of CO2. CONCLUSIONS: The results indicate that a high resting partial pressure of CO2 augments the effects of high sodium intake on plasma volume, levels of endogenous digitalis-like factors, and blood pressure in young normotensive humans.

Resting end-tidal CO2 association with age, gender, and personality.

OBJECTIVES: A previous study found that individuals with blood pressure sensitivity to high sodium intake tend to have a high resting partial pressure of end-tidal CO2 (PetCO2). The present study analyzed the test-retest reliability of individual PetCO2 over 6 months, and the association of individual PetCO2 with age, gender, and personality characteristics. METHODS: PetCO2 of 104 men and women (mean ages 42.1+/-1.5 years) was monitored via a respiratory gas monitor for 25 minutes during each of three sessions over an 11-day interval, and 59 subjects also participated in a 25-minute follow-up session 261+/-10 days later. Each subject completed the NEO Personality Inventory. RESULTS: PetCO2 remained stable within and between monitoring sessions over a 6-month period. PetCO2 was higher in men than in women, and decreased progressively over the life span. PetCO2 was not correlated with the Extraversion, Openness, Agreeableness, or Conscientiousness Scales of the NEO Personality Inventory, but was highly positively associated with the Neuroticism Scale of the NEO Personality Inventory, and with its subscales. CONCLUSIONS: High resting end-tidal CO2 tends to be a stable individual characteristic that is accompanied by a tendency to worry and experience negative emotions.

High end tidal CO2 association with blood pressure response to sodium loading in older adults.

OBJECTIVE: To test the hypothesis that blood pressure of older adults with high resting end tidal CO2 (PETCO2) is sensitive to high dietary intake of sodium chloride. DESIGN AND METHODS: Forty-four Caucasian men and women, aged 41-79 years (mean +/- SEM 55.5 +/- 1.4), restricted their dietary intake of sodium chloride for 11 days and ingested sodium chloride capsules (an additional 190 mmol sodium/day) during the last seven of those days. On days 1, 4 and 11, resting PETCO2 and blood pressure were monitored for 25 min in the laboratory, followed by ambulatory blood pressure monitoring in the natural environment for 24 h. Overnight urine samples were obtained at days 4 and 11 to estimate excretion of sodium and of an endogenous digitalis-like factor (EDLF) that is sensitive to changes in plasma volume. RESULTS: Individual resting PETCO2 remained stable within and between laboratory monitoring sessions and was correlated with urinary excretion of the endogenous digitalis-like factor, both before and after the period of high sodium intake. The high-sodium diet was associated with increased urinary sodium excretion and body weight in all quartiles of PETCO2. The high-sodium diet produced significant increases in resting and in 24 h systolic blood pressures in the upper two quartiles of the PETCO2 distribution, and significant increases in resting and in 24 h diastolic blood pressures in the highest PETCO2 quartile only. CONCLUSION: These findings indicate blood pressure sensitivity to sodium loading is differentially associated with high resting PETCO2 in older adults. A high PETCO2 may be an index of a dynamic steady state that influences sodium transport mechanisms.