Faculty Bibliography

At a news conference yesterday, Hopkins officials said that they did not receive the Nov. 30 recall letter until late January, because instead of being sent to the department that used the bronchoscopes, it was addressed to a loading dock at another department across the street. The letter had a return receipt requested. No one had signed for it, and as far as they knew, Hopkins officials said, Olympus had not followed up. In the meantime, doctors at Hopkins, like those in Tennessee, had begun to notice an unusually high rate of pseudomonas infections among patients exposed to bronchoscopes. Hopkins began its own investigation and developed a culturing technique based on running fluid backward through the scope to detect the bacteria. Dr. [Paul Scheel] said doctors at Hopkins began calling other hospitals to warn them of the problem, to tell them how to culture the bacteria and to alert them to the recall. He said mention of the recall was usually greeted by a long silence and then the question, ''What recall?''

A cohort of 56 patients infected with related strains of Mycobacterium tuberculosis, the S75 group, was identified in a New Jersey population-based study of all isolates with a low number of copies of the insertion element IS6110. Genotyping was combined with surveillance data to identify the S75 group and to elucidate its recent evolution. The S75 group had similar demographic and geographic characteristics. Seventeen persons (30%) were linked epidemiologically. The S75 group was segregated from other low-copy-number isolates on the basis of several independent molecular methods. This group included 3 IS6110 genotype variants: BE, H6, and C28, containing 1, 2, and 3 IS6110 insertions, respectively. IS6110 insertion site mapping and comparative sequence analysis strongly suggest a stepwise acquisition of IS6110 elements from BE to H6 to C28. S75 represents a locally produced strain cluster that has recently evolved. The combination of multiple molecular tools with traditional epidemiology provides novel insights into dissemination, local transmission, and evolution of M. tuberculosis

Early events in the response of cells to lipopolysaccharide (LPS) include activation of NF-kappaB and stress-activated MAP kinase p38. Recent studies have shown that the human Toll-like receptor 2 (TLR2) mediates activation of NF-kappaB in response to commercial preparations of LPS (comLPS), membrane lipoproteins, and Gram-positive bacterial products. Here, we show that expression of TLR2 in human embryonic kidney 293 cells enabled p38 phosphorylation in response to comLPS, a synthetic bacterial lipoprotein, and B. subtilis. Activation of p38 was confirmed by an in vitro kinase assay using ATF2 as substrate and by an assay measuring activation of the downstream effector of p38, MAP kinase-activated protein kinase in cells. Thus, TLR2 initiated the signaling pathway for p38 in response to bacterial products.

BACKGROUND: The response of tumors to chemotherapy (CHT) exhibits wide individual variations. PATIENTS AND METHODS: We examined the incidence of polymorphic TNF genes in 61 patients treated for Hodgkin lymphoma. RESULTS: During treatment, the patients were divided as responders or non-responders, depending upon the amount of CHT required for a clinical eradication of the tumor. The incidence of TNFa4, a microsatellite allele associated with low TNF production in leukocytes, was significantly higher in responders than in non-responders (25.7% vs 0 %, p=0.04). We also examined the incidence of tumor relapses 2-5 years after treatment. The incidence of TNFa4 was also significantly higher in patients with relapses, than in those without relapses (41.1% vs 9.3%, p=0.007). CONCLUSION: These results indicate that TNFa4 is a marker of resistance of Hodgkin lymphoma to chemotherapy and most probably is a marker of bad prognosis.

Cryptococcus neoformans, an encapsulated yeast, is a common cause of life-threatening meningoencephalitis in immunosuppressed patients. We previously observed that administration of a monoclonal antibody (MAb) to the capsular polysaccharide to mice with pulmonary infection prolonged survival and enhanced granulomatous inflammation without reducing lung CFU. To understand the mechanism of MAb action, we studied leukocyte recruitment and cytokine profiles in lungs of A/JCr mice. B lymphocytes were the predominant cell type in lung infiltrates, comprising 15 to 30% of the leukocytes. Despite alterations in histological appearance, fluorescence-activated cell sorter analysis revealed no significant difference in total numbers of lung leukocytes in MAb-treated mice and controls. Differences in the immune response to C. neoformans between MAb-treated mice and controls included (i) an increase in the percentage of granulocytes among lung leukocytes on day 14, (ii) higher macrophage surface expression of CD86 on day 28, (iii) larger amounts of IL-10 in lung homogenates at day 7, (iv) a trend toward smaller amounts of gamma interferon mRNA and protein on day 7, and (v) a smaller increase in the levels of interleukin-4 mRNA and protein on day 7. Hence, the immune responses to C. neoformans infection in the presence and absence of specific antibody were qualitatively similar, and antibody administration was associated with several subtle quantitative differences in immune response parameters that could translate into enhanced survival. MAb may function partly by down-regulating the inflammatory response and reducing host damage. Our findings demonstrate unexpected complexity in the interaction between specific MAb and other components of the host immune response.

Breast cancer activism has become a fixture in the United States, where fundraising events are ubiquitous and government financing of research into the disease has skyrocketed. Activists in other countries are now reporting similar accomplishments. Here, predominantly using the United States as a case study, I analyse the recent successes of breast cancer activism. I also raise a series of questions about the future goals of activism.

This study evaluates the effects of the American Heart Association's Heart At Work program on cardiovascular disease risk factor awareness, self-efficacy, and health behaviors. A prospective, quasi-experimental research design was used to assess the impact of the program at two factory sites (one intervention and one control). A total of 633 employees participated. Intervention site respondents significantly improved their knowledge of blood pressure management, the relationship between nutrition and cardiovascular disease, and heart attack risk factors. They also were more likely to begin treatment for hypertension, to report fewer sick days, and to have plans to improve their diet and lose weight. These findings suggest that the Heart At Work program had a favorable overall impact.

Lamm and Secor discuss common causes of headaches in people over the age of 40, noting that headaches in older people may be a sign of systemic disease. Headaches could be caused by temporal arteritis or cervical spondylosis

Her team used data from 25 states where H.I.V. infections are monitored to create a mathematical model to predict H.I.V. diagnosis in the remaining states. From the model, they also estimated that a quarter of infected people might not know they were infected. To improve care, the agency has begun public campaigns to increase the number of people who get H.I.V. tests. It is also urging wider use of a rapid H.I.V. test so individuals can get the results on the day they visit a clinic rather than waiting a week or longer, Dr. [Harold W. Jaffe] said. Also, the agency will urge hospitals to follow a guideline to make H.I.V. testing more of a routine part of health care. The recommendation, which was issued in 1993, calls on hospitals where at least 1 percent of the patient population has AIDS to consider offering H.I.V. testing to patients 15 to 54 years old