Faculty Bibliography

Targeted IS6110-based RFLP genotyping can be applied to rapidly identify specific groups of biomedically/epidemiologically relevant Mycobacterium tuberculosis clinical isolates. One such group is the W-Beijing strain family (also known as Beijing/W), implicated in significant nosocomial and community outbreaks worldwide. Using previously defined criteria, we developed a simple and accurate method to identify members of the W-Beijing family, based on rehybridization of Southern blot membranes used previously in routine IS6110 DNA fingerprint analysis. The hybridization probe constructed ('W-Beijing polyprobe') contains the PCR-amplified fragments specific for three M. tuberculosis chromosomal loci used for the identification of W-Beijing strains. The targets include the dnaA-dnaN and NTF regions and the direct repeat locus. A total of 526 selected clinical isolates (representative of 253 different IS6110-defined strain types) were analyzed using the W-Beijing polyprobe. A total of 148 isolates from this collection were found to be members of the W-Beijing phylogenetic lineage, comprising 106 strains from the W-Beijing family (46 clusters) and 42 related isolates. Rehybridization results were confirmed by computer-assisted analysis. The sensitivity and specificity of this method were estimated at 98.7% and 99.7%, respectively. This study demonstrates that the W-Beijing polyprobe can accurately and reliably discriminate members of the W-Beijing phylogenetic lineage and the W-Beijing family of M. tuberculosis strains

The initial host response to Mycobacterium tuberculosis is driven by innate immunity. For this study, we examined the ability of 18 recent clinical isolates and 5 reference strains to survive and replicate in the context of host innate immunity by using whole blood culture. Six healthy tuberculin-negative volunteers served as subjects. H(37)Ra showed the least capacity to replicate of any of the strains tested, decreasing in viability 1.3 log CFU during 72 h of whole blood culture, whereas H(37)Rv increased 0.32 log. Clinical isolates varied greatly in their ability to replicate in blood cells, ranging from -0.4 to +0.8 log (P < 0.001). Four showed significantly more growth than H(37)Rv, and one showed significantly reduced growth. Host mechanisms for restricting intracellular mycobacterial growth were more effective during the first 24 h of whole blood culture than during the 24- to 72-h period. Certain mycobacterial isolates appeared preferentially able to withstand host defenses during each of these intervals. Although there was relatively more homogeneity among subjects than among strains, one of the six subjects showed a reduced capacity to restrict intracellular mycobacterial growth due to a defect expressed during the first 24 h of culture. Our findings indicate substantial variability in the capacity of clinical tuberculosis isolates to replicate in host cells in the face of innate host immunity

Anabolic steroids were developed in the late 1930s, primarily to treat hypogonadism. Scientists discovered these steroids caused muscle growth in animals, which led to use of the compounds by bodybuilders. In Germany in the 1930s, experiments were conducted on dogs; steroids were subsequently given to German soldiers and prisoners during World War II. In the 1950s, Russians began to dominate the sport of power lifting, and it was shown that most of these athletes were using steroids containing testosterone. An American physician, Dr. John Ziegler, then created a selective form of anabolic steroids that was available on the open market. Not all bulking up comes from anabolic steroids. Human growth hormone, which is made by the pituitary gland in the brain and does not contain sex hormones or steroids, can cause increased muscle mass and weight gain. [Gary Wadler] says that one of the main motivations for abusing synthetic human growth hormone is that no urine tests exist, so a user may elude detection. There is a blood test for growth hormone but it's rarely used and is not mandated in professional sports. The only true medical indication for growth hormone is a deficiency in either childhood or adulthood. Studies have shown that the unregulated use of the drug as an anti-aging agent carries an increased risk of developing diabetes

No cases of influenza from the strain known as A(H2N2), which caused the Asian flu pandemic in 1957, have been detected anywhere in the world, said the official, Dr. Julie L. Gerberding, who directs the Centers for Disease Control and Prevention in Atlanta. Meridian Bioscience Inc., in Cincinnati, shipped the samples beginning last fall under contract with the College of American Pathologists as part of the group's proficiency testing program. Dr. Jared N. Schwartz, an official of the college, has said that when Meridian checked a United States government manual, its team found that the A(H2N2) strain could be sent to laboratories as a biosafety level 2 microbe, the second-lowest in a four-class danger rating system

PURPOSE/OBJECTIVE:There are few treatment options for patients with metastasized or inoperable endocrine gastroenteropancreatic (GEP) tumors. Chemotherapy can be effective, but the response is usually less than 1 year. Here, we present the results of treatment with a radiolabeled somatostatin analog, [177Lu-DOTA0,Tyr3]octreotate (177Lu-octreotate). PATIENTS AND METHODS/METHODS:One hundred thirty-one patients with somatostatin receptor-positive tumors were treated with up to a cumulative dose of 600 to 800 mCi (22.2 to 29.6 GBq) of 177Lu-octreotate. RESULTS:One patient developed renal insufficiency, and another patient developed hepatorenal syndrome. Creatinine clearance did not change significantly in the other patients. WHO hematologic toxicity grade 3 or 4 occurred after less than 2% of the administrations. We observed complete remission in three patients (2%), partial remission in 32 patients (26%), minor response (tumor diameter decrease of 25% to 50%) in 24 patients (19%), stable disease (SD) in 44 patients (35%), and progressive disease (PD) in 22 patients (18%). Higher remission rates were positively correlated with high uptake on pretherapy somatostatin receptor imaging and a limited number of liver metastases, whereas PD was significantly more frequent in patients with a low performance score and extensive disease. Median time to progression in 103 patients who either had SD or tumor regression was more than 36 months. CONCLUSION/CONCLUSIONS:Treatment with 177Lu-octreotate results in tumor remission in a high percentage of patients with GEP tumors. Serious side effects are rare. The median time to progression compares favorably with chemotherapy. Results are better in patients with a limited tumor load. Therefore, early treatment, even in patients who have no PD, may be better.

A series of novel ligands for the glucocorticoid receptor containing two heterocycles were synthesized. These compounds were investigated for a dissociative profile using transrepression and transactivation assays. Several compounds were tested in vivo and showed the ability to reduce inflammation in a mouse.

This parasitic infection usually is transmitted through the bite of the kissing bug (also known as the reduviid bug and the triatomine bug). The insect lives in cracks and holes in poor housing, where it bites people, often on the face, while they sleep. Occasionally, Chagas' is transmitted through blood transfusions, organ transplants, and from mother to child at birth. Recently, Brazilian health officials reported a widespread outbreak in which [Carlos Chagas]' apparently was transmitted orally through contaminated sugar cane juice. Brazil has banned the sale of the juice

Immediately, he said, investigators tracked down the woman to determine whether she was in fact infected with the strain. They asked her about her recent travels, contact with birds and when she first felt sick. They determined quickly that her respiratory symptoms were not from influenza. The origin of the 1957 strain remained mysterious. Dr. [Frank Plummer] said his team called the center in Atlanta on March 26. By April 8, Canadian epidemiologists had traced the strain to the specimens sent out by the College of American Pathologists in Northfield, Ill., which had ordered them from Meridian. Dr. Jared N. Schwartz, a microbiologist and official of the College of American Pathologists, said his group asked Meridian to include a type A influenza virus in the test kit, but did not specify which strain. When Meridian checked a United States government manual, he said, its team found that the A(H2N2) strain could be sent to laboratories as a biosafety Level 2 microbe, the second-lowest level of danger in a four-class rating. Dr. Plummer agreed, saying, ''Meridian made an error in choosing the A(H2N2) virus to send out.'' The strain was listed as A(H3N2), a common strain, on the permit forms for customs, Dr. Plummer said