Faculty Bibliography

Protective immunity against pulmonary tuberculosis (TB) is characterized by the formation in the lungs of granulomas consisting of macrophages and activated T cells producing tumor necrosis factor alpha and gamma interferon, both required for the activation of the phagocytes. In 90% of immunocompetent humans, this response controls the infection. To understand why immunity fails in the other 10%, we studied the lungs of six patients who underwent surgery for incurable TB. Histologic examination of different lung lesions revealed heterogeneous morphology and distribution of acid-fast bacilli; only at the surface of cavities, i.e., in granulomas with a patent connection to the airways, were there numerous bacilli. The mutation profile of the isolates suggested that a single founder strain of Mycobacterium tuberculosis may undergo genetic changes during treatment, leading to acquisition of additional drug resistance independently in discrete physical locales. Additional drug resistance was preferentially observed at the cavity surface. Cytokine gene expression revealed that failure to control the bacilli was not associated with a generalized suppression of cellular immunity, since cytokine mRNA was up regulated in all lesions tested. Rather, a selective absence of CD4(+) and CD8(+) T cells was noted at the luminal surface of the cavity, preventing direct T-cell-macrophage interactions at this site, probably allowing luminal phagocytes to remain permissive for bacillary growth. In contrast, in the perinecrotic zone of the granulomas, the two cell types colocalized and bacillary numbers were substantially lower, suggesting that in this microenvironment an efficient bacteriostatic or bactericidal phagocyte population was generated

Human tuberculosis (TB) is caused by the bacillus Mycobacterium tuberculosis, a subspecies of the M. tuberculosis complex (MTC) of mycobacteria. Postgenomic dissection of the M. tuberculosis proteome is ongoing and critical to furthering our understanding of factors mediating M. tuberculosis pathobiology. Towards this end, a 32-kDa putative glyoxalase in the culture filtrate (CF) of growing M. tuberculosis (originally annotated as Rv0577 and hereafter designated CFP32) was identified, cloned, and characterized. The cfp32 gene is MTC restricted, and the gene product is expressed ex vivo as determined by the respective Southern and Western blot testing of an assortment of mycobacteria. Moreover, the cfp32 gene sequence is conserved within the MTC, as no polymorphisms were found in the tested cfp32 PCR products upon sequence analysis. Western blotting of M. tuberculosis subcellular fractions localized CFP32 predominantly to the CF and cytosolic compartments. Data to support the in vivo expression of CFP32 were provided by the serum recognition of recombinant CFP32 in 32% of TB patients by enzyme-linked immunosorbent assay (ELISA) as well as the direct detection of CFP32 by ELISA in the induced sputum samples from 56% of pulmonary TB patients. Of greatest interest was the observation that, per sample, sputum CFP32 levels (a potential indicator of increasing bacterial burden) correlated with levels of expression in sputum of interleukin-10 (an immunosuppressive cytokine and a putative contributing factor to disease progression) but not levels of gamma interferon (a key cytokine in the protective immune response in TB), as measured by ELISA. Combined, these data suggest that CFP32 serves a necessary biological function(s) in tubercle bacilli and may contribute to the M. tuberculosis pathogenic mechanism. Overall, CFP32 is an attractive target for drug and vaccine design as well as new diagnostic strategies

Releasing the agency's annual report before World AIDS Day on Monday, [Peter Piot] acknowledged that greater financing and stronger political commitments had given the battle against AIDS more momentum. But he singled out nations that were way behind in tackling AIDS. Chiding Russia for not making the political commitment other countries have made for AIDS, Piot said it allocated only a few million dollars for AIDS and was still dealing with it at the level of a deputy minister of health. Piot said he welcomed the South African government's plan, announced last week, to provide antiretroviral drugs to AIDS patients, as well as an earlier announcement by former President Bill Clinton that he had brokered an agreement under which drug companies agreed to lower the price of AIDS drugs for many countries. The World Health Organization plans to deliver antiretroviral drugs to three million people by 2005

While the pace of the battle against AIDS is picking up, efforts to stem the epidemic are 'entirely inadequate' for the health emergency that is 'continuing to spiral out of control,' the director of the U.N. AIDS program said Tuesday. He singled out nations that were way behind in tackling AIDS. 'Many countries do not take AIDS seriously, and that is particularly the case of Russia, all the countries of the former Soviet Union, and several Asian countries,' [Peter Piot] said in a teleconference

The global epidemic of AIDS shows no sign of abating, he said, and measured against the scale of the global epidemic, the current pace and scope of the world's response to AIDS fall far short of what is required. The toll from AIDS this year is expected to be the highest ever, [Peter Piot] said in a telephone news conference, with the virus infecting 5 million new people and killing 3 million. Around the world, an estimated 40 million people are now infected with the AIDS virus

The epidemic shows no sign of abating, said the director, Dr. Peter Piot, adding, ''Measured against the scale of the global epidemic, the current pace and scope of the world's response to AIDS fall far short of what is required.'' He chided nations that were way behind in tackling AIDS -- though not, in every case, by name. ''Many countries do not take AIDS seriously, and that is particularly the case of Russia, all the countries of the former Soviet Union, and several Asian countries,'' Dr. Piot said in a teleconference. Dr. Piot said he welcomed the South African government's new plan to provide antiretroviral drugs to patients, as well as an earlier announcement by former President Bill Clinton that he had brokered an agreement with drug companies to lower the price of AIDS drugs for many countries. The World Health Organization plans to deliver antiretroviral drugs to three million people by 2005

In releasing the agency's annual report in advance of World AIDS Day on Monday, [Peter Piot] acknowledged that greater funding and stronger political commitments had moved the battle against AIDS into higher gear. But he singled out nations that were way behind in tackling AIDS. 'Many countries do not take AIDS seriously, and that is particularly the case of Russia, all the countries of the former Soviet Union, and several Asian countries,' Piot said in a telephone news conference. An estimated 1 million Russians are infected, and 'the epidemic is growing at a fearsome rate,' the report said. Chiding Russia for not making the political commitment other countries have made for AIDS, Piot said Russia allocates 'only a few million dollars for AIDS and still deals with it at the level of a deputy minister of health.' Piot said he welcomed the South African government's plan last week to provide anti-retroviral drugs to AIDS patients as well as an earlier announcement by former President Bill Clinton that he had brokered an agreement with drug companies to lower the price of AIDS drugs for many countries. The World Health Organization plans to deliver anti-retroviral drugs to 3 million people by 2005

Chiding Russia for not making the political commitment that other countries have made for AIDS, [Peter Piot] said Russia allocates 'only a few million dollars for AIDS and still deals with it at the level of a deputy minister of health.' Piot said he welcomed a plan announced last week by South Africa's government to provide anti-retroviral drugs to AIDS patients, as well as an earlier announcement by former President Clinton that he had brokered a deal with drug companies to lower the price of AIDS medications for many countries. The World Health Organization plans to deliver anti-retroviral drugs to 3 million people by 2005. Southern Africa is home to about 30 percent of people living with HIV/AIDS worldwide, although the region has less than 2 percent of the world's population. In Botswana and Swaziland, the infection rate of HIV/AIDS among adults is 40 percent

[Alonzo Mourning], a four-time N.B.A. All-Star, ''will need a kidney transplant in the near future,'' the doctor, Gerald Appel, a kidney specialist at Columbia University, said in a telephone interview after the Nets disclosed that Mourning's career had apparently come to an end after a frustrating 12-game comeback. When he examined Mourning, a 6-foot-10 center, on Sunday, a day after Mourning scored 15 points in his best game of the season, Appel said the levels in Mourning's blood of creatinine, a measure of kidney function, and potassium were very high and that those readings, along with other chemical imbalances, led him and the Nets physicians to conclude that it was ''no longer medically safe for him to play basketball.'' With the Nets, Mourning did not have the time, nor perhaps the resiliency, to make much of an impact. His short stay with the Nets will be best remembered for the ugly confrontation he had with two Nets stars -- Kenyon Martin and Richard Jefferson -- in practice last week, a dispute in which Mourning's intensity ran head on into the very casual attitude sometimes embraced by younger Nets players