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Biomedical subjects

M Fulop

Publications and source records attributed to M Fulop.

At least 19 recordsLinked to original sources

Role of antibody to lipopolysaccharide in protection against low- and high-virulence strains of Francisella tularensis.

Mice immunised with lipopolysaccharide (LPS) from Francisella tularensis were protected against challenge with the live vaccine strain (LVS). However, when similarly immunised mice were challenged using the fully virulent F. tularensis strain Schu4, only an increase in the time to death was observed. Passive transfer of serum from LPS-immunised mice to naive mice afforded protection against F. tularensis LVS. LPS-immunised mice depleted of either CD4+ or CD8+ T-cells survived a F. tularensis LVS challenge although the rate of clearance of bacteria from the spleen was significantly reduced in the CD8+ depleted group. LPS-immunised mice boosted with F. tularensis LVS were re-challenged with F. tularensis Schu4. This cohort was significantly protected (LD(50) increased from <1 to >1000 CFU). However, passive transfer of serum did not confer protection and mice depleted of CD4+ or CD8+ T-cells did not survive.

Animals↗

Serum beta-hydroxybutyrate measurement in patients with uncontrolled diabetes mellitus.

OBJECTIVE: To assess whether routinely measuring serum beta-hydroxybutyrate (beta-OHB) concentration might help judge the severity of or assist in treating patients with suspected ketoacidosis. METHODS: Serum beta-OHB level was estimated by a standard enzymatic method in 64 episodes in adults admitted to a municipal hospital. Of the 85 specimens analyzed, 60 were taken before treatment from a nearly consecutive group of diabetic patients with ketosis, 21 were follow-up specimens, and 4 were from nondiabetic patients with ketosis. RESULTS: In the 85 specimens, the correlation between serum carbon dioxide and beta-OHB levels was -0.69, and that between anion gap and beta-OHB level was 0.75. For just the initial specimens, the respective correlation coefficients were -0.60 and 0.52. CONCLUSIONS: The correlations between serum beta-OHB and carbon dioxide levels and the anion gap were close, but not sufficiently so for the beta-OHB measurements to be routinely useful alone to assess the severity of the ketoacidosis. Full laboratory assessment of the severity and characteristics of ketoacidosis also requires knowledge of serum carbon dioxide level, anion gap, often blood pH, and ideally serum acetoacetate and lactate concentrations as well as serum beta-OHB concentration.

3-Hydroxybutyric Acid↗

Algorithms for diagnosing some electrolyte disorders.

The differential diagnosis of electrolyte disorders has traditionally been framed in terms of pathophysiology, and analysis of clinical problems has usually proceeded in the same way. However, easier access to rapid-response laboratory analysis has prompted physicians who encounter patients with serious electrolyte abnormalities to try to establish the cause by quickly obtaining further simple tests. In that vein, this article and the algorithms that are presented are intended to assist the preliminary laboratory differential diagnosis of low and high serum levels of sodium, potassium, and calcium.

Algorithms↗

Health risk behaviors among California college students.

Health risk behaviors among students attending 4-year colleges in California were examined. The Youth Risk Behavior Survey for College Students was administered in a two-stage (29 universities, 5,652 students) random sample. All campuses and 3,810 (69%) students participated in the survey. In the 30 days preceding the survey, 36.7% of the students had binged at least once while drinking; 25.3% had driven after consuming alcohol; 32% had ridden in a car with someone who had been drinking; 17.6% had used marijuana; and 6% had carried a knife, gun, or club. More than half of the students who were sexually active and not married or living with a primary partner had not used a condom the last time they had sexual intercourse. Only 5% of regular bicycle riders always wore a helmet. Fewer than half (44%) reported aerobic physical activity on 3 or more of the preceding 7 days. The results of this study indicate a substantial amount of serious, risky health behaviors among California college students.

Adolescent↗

Binge drinking among college students: a comparison of California with other states.

California college students (1,864 students from 15 colleges) were compared with students who participated in the Harvard School of Public Health College Alcohol Study, which surveyed 17,592 students in 140 colleges nationwide. California college students, in comparison with the remainder of the nation, were less frequent drinkers; less frequent binge drinkers; exhibited fewer personal problems and risks associated with heavy episodic drinking, including drinking and driving; and reported fewer "secondhand" effects of binge drinking, such as being physically assaulted or experiencing an unwanted sexual advance. Many of these differences appear to be related to the California college students' being older, more likely to be married, and less likely to live on campus than those in the Harvard study. The findings suggest that, in developing programs tailored to local needs, there is significant value in augmenting national surveillance of college student health risk behaviors with the development of regional, state, and local surveillance systems.

Adolescent↗

Principles for assuring the health of college students: a California perspective.

Given the rapidity of change in both higher education and health care, re-examining the values and precepts that undergird the profession of college health is an ongoing need. Reported in this article are the results of a structured process in which a group of college health professionals from California, along with others interested in the health of college students, examined several trends affecting higher education and health; considered possible scenarios for these sectors; created a shared vision for the future of college health; and developed strategies useful in attaining that vision. The results of these deliberations are presented as a set of principles that, if followed, should increase the likelihood that college health centers will be responsive to user needs. Although the article is based on a California-based conference, the principles discussed are almost certainly valuable for all in college health.

Adolescent↗

A guide for predicting arterial CO2 tension in metabolic acidosis.

This presentation examines the relation of arterial CO2 tension to the severity of acidemia in three large groups of cases of diabetic ketoacidosis, totalling 405 episodes. In particular, it evaluates the previously reported anecdotal observation that PaCO2 (in torr) in such patients is usually numerically close to the two-digit number to the right of the pH decimal point, down to a pH of 7.10-7.15. The relations between measured arterial CO2 tension levels and calculated plasma bicarbonate concentration in the three groups were very similar to those previously reported by others and us, the regression equations approximating PaCO2 = 1.5 x [HCO3-] + 8. Further, in the 262 episodes with blood pH 7.10-7.37, down to a pH of 7.10-7.15, the average PaCO2 in torr often did approximate the two-digit number to the right of the decimal point in the pH value. This relation provides a quick and easily remembered alternative guide for predicting the approximate expected PaCO2 in patients with metabolic acidosis. The basis for this apparently fortuitous relation between PaCO2 and blood pH may be the closely similar correlation between PaCO2 and 1/cH+ (i.e., 10PH), which in turn derives from the physiologically significant relation of alveolar ventilation to blood pH, and the inverse relation between PaCO2 and alveolar ventilation.

Adult↗

Role of two outer membrane antigens in the induction of protective immunity against Francisella tularensis strains of different virulence.

A crude outer membrane preparation from Francisella tularensis live vaccine strain was used to immunise mice. Immunised mice were completely protected from a F. tularensis challenge. We evaluated the role of two major outer membrane antigens in the induction of protective immunity, namely lipopolysaccharide and an outer membrane protein FopA. We presented FopA to the immune system using an aromatic amino acid dependent Salmonella typhimurium as a vector. Although mice mounted an immune response to cloned FopA no significant protection was induced. However, lipopolysaccharide-immunised mice were completely protected from a F.tularensis live vaccine strain challenge. No increase in LD50 was observed using F. tularensis Schu4 as the challenge strain, although there was a significant increase in time to death. These data question the validity of the murine F. tularensis live vaccine strain model.

Animals↗

A rapid, highly sensitive method for the detection of Francisella tularensis in clinical samples using the polymerase chain reaction.

We have developed a highly sensitive method for detection of Francisella tularensis in clinical samples based on a nested polymerase chain reaction (PCR) for the FopA gene. Mice infected with F. tularensis were killed at 24-hr intervals, and the DNA from blood and spleens was extracted by a variety of methods and analyzed by PCR. The best method, based on the ability of DNA to bind to silica in the presence of guanidine thiocyanate, yielded amplifiable DNA without dilution of the murine tissue samples. Francisella tularensis in infected murine spleens and culture-positive blood samples was reliably detected by nested PCR following this extraction procedure. We believe this technique has significant advantages over traditional methods for diagnosing F. tularensis infection in terms of speed, ease of use, reproducibility, and safety.

Animals↗

Role of lipopolysaccharide and a major outer membrane protein from Francisella tularensis in the induction of immunity against tularemia.

A crude outer membrane preparation from Francisella tularensis Live Vaccine Strain (LVS) was used to immunize mice. Immunized mice were completely protected from a F. tularensis challenge. We evaluated the role of two major outer membrane antigens in the induction of protective immunity, namely lipopolysaccharide and an outer membrane protein FopA. We presented FopA to the immune system using an aromatic amino acid-dependent Salmonella typhimurium as a vector. Although mice mounted an immune response to cloned FopA no significant protection was induced. However, LPS immunized mice were completely protected. We conclude that LPS is a major protective antigen whereas FopA has a limited or no role in the induction of protective immunity.

Animals↗

Effect of different plasmids on colonization of mouse tissues by the aromatic amino acid dependent Salmonella typhimurium SL 3261.

The stability of plasmids pBR322, pUC19 and pBluescript and their effect on bacterial colonization of mice was determined. S. typhimurium SL 3261 carrying high copy number plasmids colonized spleen and liver tissues poorly compared to low copy number plasmids. After inoculation into mice, the stability of the plasmids appeared to be inversely related to the plasmid's size and complexity. Mouse-passaging a pBluescript-based recombinant plasmid expressing the Protective Antigen of Bacillus anthracis selected for a mutant S. typhimurium strain (designated G3) that colonized at high levels and more stably maintained plasmids than S. typhimurium SL 3261. S. typhimurium G3 down-regulated the copy number of ColE1 plasmids. The significance of these data for vaccine design is discussed.

Animals↗

Bacillus anthracis protective antigen, expressed in Salmonella typhimurium SL 3261, affords protection against anthrax spore challenge.

The protective antigen (PA) gene from Bacillus anthracis has been expressed in Salmonella typhimurium SL 3261 (aroA). Expression was achieved by cloning the gene after the plac promoter in a high copy number plasmid. The recombinant PA was exported into the periplasm. This construct was unstable in vivo and also reduced the colonization ability of the host S. typhimurium. Mouse-passaging of the recombinant Salmonella resulted in a strain with enhanced colonization ability and increased stability of the plasmid in vivo. This effect appeared to be due to a reduction in copy number of the PA-encoding plasmid. Mice were vaccinated with recombinant S. typhimurium and adjuvanted PA and challenged with virulent B. anthracis. Only mice vaccinated with adjuvanted PA or orally with the mouse-passaged recombinant showed partial protection. The degree of protection observed after oral vaccination with the recombinant S. typhimurium was similar to the degree of protection afforded by adjuvanted PA and suggested that the use of S. typhimurium to deliver PA is an effective approach for inducing protection against B. anthracis. The results presented also suggest that the degree of protection demonstrated in the mouse may not fully indicate the potential of the recombinant Salmonella as an effective vaccine in other species.

Animals↗