Faculty Bibliography

Nmp4/CIZ proteins (nuclear matrix protein 4/cas interacting zinc finger protein) contribute to gene regulation in bone, blood, and testis. In osteoblasts, they govern the magnitude of gene response to osteotropic factors like parathyroid hormone (PTH). Nmp4/CIZ is recurrently involved in acute leukemia and it has been implicated in spermatogenesis. However, these conserved proteins, derived from a single gene, are expressed in numerous tissues indicative of a more generalized housekeeping function in addition to their tissue-specific roles. To address how Nmp4/CIZ expression is governed, we characterized the 5' regulatory region of the mouse Nmp4 gene, located on chromosome 6. Two adjacent promoters P(1) [-2521 nucleotide (nt)/-597 nt] and P(2) (-2521 nt/+1 nt) initiate transcription of alternative first exons (U(1) and U(2)). Both promoters lack TATA and CCAAT boxes but contain initiator sites and CpG islands. Northern analysis revealed expression of both U(1) and U(2) in numerous adult tissues consistent with the constitutive and ubiquitous activity of a housekeeping gene. Sequence analysis identified numerous potential transcription factor-binding sites significant to osteogenesis, hematopoeisis, and gonadal development. The promoters are active in both osteoblast-like cells and in the M12 B-lymphocyte cell line. Low doses of PTH attenuated P(1)/P(2) activity in osteoblast-like cells. The Nmp4/CIZ promoters are autoregulated and deletion analysis identified regions that drive P(1) and P(2) basal activities as well as regions that contain positive and negative regulatory elements affecting transcription. The Nmp4/CIZ promoters comprise a genomic regulatory architecture that supports constitutive expression as well as cell- and tissue-specific regulation.

The discoveries arose from studies undertaken out of concern that another retrovirus could emerge to mushroom into another global pandemic like AIDS. Many scientists say they believe that H.I.V., the AIDS virus, mutated from a simian virus that was transmitted from nonhuman primates to hunters and then spread widely through sex and contaminated needles. The retroviruses, named H.T.L.V.-3 and H.T.L.V.-4, for human T-lymphotropic virus, are the newest members of a class that can cause a wide spectrum of illnesses. The retrovirus numbered 1 is a cause of leukemia and inflammatory diseases, and it and H.T.L.V.-2 can lead to neurological disease, Dr. [Walid Heneine] said. Although the ultimate aim is to prevent another virus from causing an AIDS-like pandemic, Dr. Heneine said, one concern is the potential spread of the new viruses through blood transfusions. Blood banks in Africa do not test for H.T.L.V. viruses before blood and blood products are transfused, he said

In a special symposium arranged to deal with the issues raised by the New York case, Dr. [David Ho] presented his case to thousands of the world's top AIDS experts at the Hynes Convention Center. He said it was unique not only among all those the Aaron Diamond Center had ever seen, but also among all the cases cataloged in the laboratory at Los Alamos, which collects data of the gene sequences and other molecular biology information of H.I.V. isolates from around the country. Scientists can test for a number of genetic markers that indicate whether a patient is unusually susceptible to such a quick progression. Dr. Ho's team reported that it had found none of the key indicators that usually signal rapid progression of the virus. Dr. Ho said they had several more tests yet to run. But even when all the tests are complete, he said, there will still be room for doubt. ''The scientific community simply doesn't know enough about genetic markers for disease progression,'' Dr. Ho said in an interview before the presentation. ''There could be other markers that we cannot look at, so we can never exclude genetics, because the knowledge is incomplete.'' The patient is a 46-year-old gay man who tested positive for H.I.V. in December. Another test showed that the man had antibodies to H.I.V., indicating that he had been infected for more than three months, but less than 20, Dr. Ho said

Dr. David Ho, director of the Aaron Diamond AIDS Research Laboratory in Manhattan, which first identified the possible new strain, said: 'I think we have a unique convergence of a very drug- resistant virus, and this infection was very, very rapid. And this man has many, many sexual partners.' Some scientists and gay rights advocates have criticized the disclosure as premature and unnecessarily alarmist. There is little doubt that the HIV strain was resistant to drugs used to combat the AIDS virus

Health officials around the world have pointed to Uganda's success in reducing the prevalence of infections with H.I.V., the virus that causes AIDS, in recent years. President Yoweri Kaguta Museveni of Uganda, the [Bush] administration and some public health experts have credited the decline largely to a policy known as ABC, for abstinence, be faithful (monogamy) and condom use. The findings apply strictly to Rakai and cannot be extrapolated to other areas of Uganda for many reasons, Dr. [Maria J. Wawer] and a co-author, Dr. Ronald Gray of the Johns Hopkins Bloomberg School of Public Health, who is also her husband, said in interviews with reporters. One reason is that the age of first sexual intercourse varies in different areas of Uganda. Dr. [Chris Beyrer], Dr. Wawer and Dr. Gray said there was now a condom shortage in Uganda because officials had found defects in condoms imported from a country that they did not identify. The Ugandan government has stopped distribution of that country's condoms and is testing all foreign-made condoms, including those made in the United States, they said, adding that the price of condoms in Uganda has risen

Health officials around the world have pointed to Uganda's success in reducing the prevalence of infections with HIV, the virus that causes AIDS, in recent years. Uganda's President Yoweri Kaguta Museveni, the [BUSH] administration and some public health experts have credited the decline largely to a policy known as ABC -- for abstinence, be faithful (monogamy) and condom use. The findings apply strictly to Rakai and cannot be extrapolated to other areas of Uganda for many reasons, [Maria J. Wawer] and a co-author, Dr. Ronald Gray of Johns Hopkins, who is also her husband, said in interviews with reporters. One reason is that the age of first sexual intercourse varies in different areas of Uganda. [Chris Beyrer], Wawer and Gray said there now is a condom shortage in Uganda because officials have found defects in condoms imported from a country they did not identify. The Ugandan government has stopped distribution of condoms imported from that country and is testing all foreign-made condoms, including those made in the United States, they said, adding that the price of condoms in Uganda has risen

Charles King, the president of Housing Works, an AIDS support group, said the announcement could be used to demonize the gay lifestyle and accused Dr. [Thomas R. Frieden] of having wanted to change regulations regarding H.I.V. testing for a long time. The Community H.I.V./AIDS Mobilization Project, based in New York, said the link between the spread of the possible new strain and the use of crystal methamphetamine was unproven, and suggested that the city had ignored the ''underlying issues'' behind the spread of the virus, like discrimination, poor housing and unemployment. Dr. Ho, then a relatively unknown 37-year-old researcher fresh from Harvard and U.C.L.A., was hired to run the center in 1989 and immediately attracted attention. With more money at his disposal than most other research institutions, Dr. Ho became the object of envy as top-flight scientists lined up to join his center. Within a few years, Dr. Ho's team won international publicity, challenging long-held theories about AIDS and reporting new evidence about the way the AIDS virus works in the body. After Dr. Frieden disclosed the case, reports of similar cases quickly emerged, some of which had been published earlier. For example, Dr. Julio Montaner, a professor of medicine at the University of British Columbia in Vancouver, reported in 2003 in the scientific journal AIDS that two men with a highly drug-resistant strain of H.I.V. might have progressed rapidly to AIDS. Dr. Ho did not contact Dr. Montaner about the case until three days after Dr. Frieden's news conference

In 2003, the incidence of tuberculosis (TB) cases in the United States declined for the eleventh consecutive year to a record low of 5.1 cases per 100,000 population. In 2003, 6.3% of reported TB cases in the United States were among homeless persons. Compared with the general population, this group has a greater risk for latent TB infection (LTBI) and progression to active disease. This report summarizes a recent outbreak of TB and highlights the challenges of preventing TB among homeless persons, particularly when multiple chains of transmission are occurring and multiple jurisdictions are involved. The findings underscore the complementary role of rapid DNA genotyping in the detection of possible TB transmission in homeless populations. To ensure early detection of unsuspected TB transmission in homeless populations, health department TB-control programs are encouraged to use CDC's universal Mycobacterium tuberculosis rapid genotyping system.

Dr. Guthrie S. Birkhead, director of the New York State Health Department's AIDS Institute, said he discussed the measure with Dr. [Thomas R. Frieden] and was open to considering changing state law. However, Dr. Birkhead and Dr. Frieden said they recognized that because laboratories do not use a standard format to report test results, collecting the data could prove extremely difficult. Immediately after the rare H.I.V. strain was reported to the department, Dr. Frieden said he asked the dozen or so laboratories licensed by the state to check their records for any other patients with the same strain of the virus. While proposals to restructure the AIDS bureau have been in the planning stages for months, they gained added urgency after the city announced last week that a strain of H.I.V. had been found that showed resistance to multiple drugs and possibly led to the rapid onset of AIDS in a New York City man, perhaps in as few as two months

Dr. Thomas R. Frieden, the commissioner of the New York City Department of Health and Mental Hygiene, faced that conundrum last Friday. At a news conference, Dr. Frieden announced that a New York City man in his mid-40's had the first diagnosed strain of H.I.V. that showed both resistance to multiple classes of antiretroviral drugs and a rapid progression from infection to AIDS. Doctors have in the past reported each of these components separately, but not in combination. He said that AIDS and H.I.V. had been viewed as a cause by advocacy groups and as a scientific challenge by researchers, and that that was appropriate. ''But we really have not applied the principles of epidemic control to H.I.V./AIDS to a remarkably great extent because of the population and the political context in which it arose,'' Dr. Frieden said. In alerting medical workers, Dr. Frieden said his hope was that more infected people would be found in the early stages of H.I.V. infection. It is at that time when the risk of transmission of the virus is extremely great because there are large amounts of H.I.V. in the blood. Also, Dr. Frieden said, most people change their risk behavior upon learning that they are infected