Bone marrow CD34(+) cells and megakaryoblasts secrete beta-chemokines that block infection of hematopoietic cells by M-tropic R5 HIV.

CD34(+) cells are nonpermissive to infection by HIV strains X4 and R5, despite the fact that many CD34(+) cells express high levels of the viral receptor protein CD4 and the coreceptor CXCR4 on their surface. In these cells, the co-receptor CCR5 protein, which, like CXCR4, is a chemokine receptor, is detected mainly intracellularly. We hypothesized that CD34(+) cells secrete CCR5-binding chemokines and that these factors interfere with HIV R5 interactions with these cells, possibly by binding CCR5 or by inducing its internalization. We found that human CD34(+) cells and CD34(+)KIT(+) cells, which are enriched in myeloid progenitor cells, expressed and secreted the CCR5 ligands RANTES, MIP-1alpha, and MIP-1beta and that IFN-gamma stimulated expression of these chemokines. In contrast, SDF-1, a CXCR4 ligand, was not detectable in the CD34(+)KIT(+) cells, even by RT-PCR. Conditioned media from CD34(+) cell culture significantly protected the T lymphocyte cell line PB-1 from infection by R5 but not X4 strains of HIV. Interestingly, the secretion of endogenous chemokines decreased with the maturation of CD34(+) cells, although ex vivo, expanded megakaryoblasts still secreted a significant amount of RANTES. Synthesis of CCR5-binding chemokines by human CD34(+) cells and megakaryoblasts therefore largely determines the susceptibility of these cells to infection by R5 HIV strains. We postulate that therapeutic agents that induce the endogenous synthesis of chemokines in human hematopoietic cells may protect these cells from HIV infection.

Correlation of behavioral and cerebrovascular functions in the aging rat.

Regional cerebral blood flow (rCBF), maze performance and the influence of environmental enrichment on these parameters were studied in Sprague-Dawley rats aged 6, 12 and 24 months. Learning ability in a complex sequential T-maze (Stone maze) progressively declined with increasing age in rats which were normally housed in standard caging. Environmental enrichment significantly improved maze performance but did not prevent the age-dependent impairment. Following completion of the learning studies, rCBF was measured in each of 13 brain regions in conscious, unrestrained, resting animals. In the absence of any significant change in cardiac output over the entire age range, rCBF was lower in all brain regions by an average of 16% in 12-14 month old rats and 8% in aged rats (24-26 months old); the occipital cortex, inferior and superior colliculi and hypothalamus were particularly affected regions in both age groups. The sharp reduction of rCBF that occurred between 6 and 12 months of age did not reflect, and probably preceded the progressive decline in maze performance. Such highly significant age-related changes in rCBF were not affected, however, by environmental enrichment procedures. This contrasts with the substantial influence of enrichment on maze performance. Finally, mean brain blood flow and mean cortical blood flow correlated inversely and significantly with average daily numbers of errors made by 24 month old rats during Stone maze acquisition.

Gainsharing: a call for guidance.

Gainsharing is a device by which hospitals and physicians share in the development, implementation, and proceeds resulting from the mechanisms to make the provision of healthcare more efficient and cost effective. The goal of gainsharing programs is to save hospitals money while maintaining the same or better quality of care--a goal that will ultimately result in both better care and lower expenses for payors and for society as a whole. Nevertheless, the OIG has ruled that gainsharing programs are per se illegal. This Article analyzes the reasons behind the OIG's determination and argues that, contrary to the OIG's conclusion, the advisory opinion process is legally and practically the best way to deal with the issues raised by gainsharing programs.

Deaths: final data for 1998.

OBJECTIVES: This report presents final 1998 data on U.S. deaths and death rates according to demographic and medical characteristics such as age, sex, race, Hispanic origin, marital status, educational attainment, injury at work, State of residence, and cause of death. Trends and patterns in general mortality, life expectancy, and infant and maternal mortality are also described. A previous report presented preliminary mortality data for 1998. METHODS: In 1998 a total of 2,337,256 deaths were reported in the United States. This report presents descriptive tabulations of information reported on the death certificates. Death certificates are completed by funeral directors, attending physicians, medical examiners, and coroners. Original records are filed in the State registration offices. Statistical information is compiled into a national data base through the Vital Statistics Cooperative Program of the National Center for Health Statistics (NCHS), Centers for Disease Control and Prevention. RESULTS: The 1998 age-adjusted death rate for the United States decreased to an all-time low of 471.7 deaths per 100,000 standard population, and life expectancy at birth increased to a record high of 76.7 years. Of the 15 leading causes of death in 1998, the largest decline from the previous year--9.5 percent--in age-adjusted death rates was for Atherosclerosis (atherosclerosis). Human immunodeficiency virus (HIV) infection dropped from among the 15 leading causes for the first time since 1987. The age-adjusted death rate for firearm injuries decreased for the fifth consecutive year, declining 7.4 percent between 1997 and 1998. Among all causes of death, age-specific death rates rose for those under 1 year but declined for all other age groups, although the decline for children aged 1-4 years was not significant. The infant mortality rate was unchanged from 1997 at 7.2 infant deaths per 1,000 live births. CONCLUSIONS: The overall improvements in general mortality and life expectancy in 1998 continue the long-term downward trend in U.S. mortality. Although unchanged from 1997, the trend in U.S. infant mortality is of steady declines over the past four decades.

Deaths: final data for 1997.

OBJECTIVES: This report presents final 1997 data on U.S. deaths and death rates according to demographic and medical characteristics such as age, sex, race, Hispanic origin, marital status, educational attainment, injury at work, State of residence, and cause of death. Trends and patterns in general mortality, life expectancy, and infant and maternal mortality are also described. A previous report presented preliminary mortality data for 1997. METHODS: In 1997 a total of 2,314,245 deaths were reported in the United States. This report presents descriptive tabulations of information reported on the death certificates. Death certificates are completed by funeral directors, attending physicians, medical examiners, and coroners. Original records are filed in the State registration offices. Statistical information is compiled into a national data base through the Vital Statistics Cooperative Program of the National Center for Health Statistics (NCHS), Centers for Disease Control and Prevention. RESULTS: The 1997 age-adjusted death rate for the United States decreased to an all-time low of 479.1 deaths per 100,000 standard population, and life expectancy at birth increased to a record high of 76.5 years. The 15 leading causes of death remained the same as in 1996, although Human immunodeficiency virus (HIV) infection plummeted from the 8th leading cause of death to the 14th leading cause. Some of the 8th-14th leading causes of death shifted positions. HIV infection remained the leading cause of death for black persons aged 25-44 years. The largest decline in age-adjusted death rates among the leading causes of death was for HIV infection, which dropped 47.7 percent between 1996 and 1997. Mortality declined for all age groups, except for persons aged 85 and over. The infant mortality rate reached a record low of 7.2 infant deaths per 1,000 live births in 1997 although the decline in the rate from 1996 was not statistically significant. CONCLUSIONS: The overall improvements in general mortality and life expectancy in 1997 continue the long-term downward trend in U.S. mortality. The trend in U.S. infant mortality is of steady declines over the past four decades.

Deaths: final data for 1996.

OBJECTIVES: This report presents 1996 data on U.S. deaths and death rates according to demographic and medical characteristics such as age, sex, race, Hispanic origin, marital status, educational attainment, injury at work, State of residence, and cause of death. Trends and patterns in general mortality, life expectancy, and infant and maternal mortality are also described. METHODS: In 1996 a total of 2,314,690 deaths were reported in the United States. This report presents descriptive tabulations of information reported on the death certificates. Death certificates are completed by funeral directors, attending physicians, medical examiners, and coroners. Original records are filed in the state registration offices. Statistical information is compiled into a national data base through the Vital Statistics Cooperative Program of the National Center for Health Statistics, Centers for Disease Control and Prevention. Changes between 1995 and 1996 in death rates and differences in death rates across demographic groups in 1996 are tested for statistical significance. Unless otherwise specified reported differences are statistically significant. RESULTS: The 1996 age-adjusted death rate for the United States decreased, reaching an all-time low of 491.6 deaths per 100,000 standard population, and life expectancy at birth increased by 0.3 years to 76.1 years, a record high. The 15 leading causes of death remained the same as in 1995, although there were changes in the ranking of some causes. Replacing homicide, septicemia became the 12th leading cause of death, and Alzheimer's disease moved from the 14th to the 13th leading cause. For the third consecutive year, the number of homicide deaths dropped, making it the 14th leading cause of death. Mortality declined for all age groups, including persons aged 85 and over. The largest decline in age-adjusted death rates among the leading causes of death was for Human immunodeficiency virus infection, which dropped 28.8 percent in 1996, compared with the previous year. The infant mortality rate declined by 4 percent to a record low of 7.3 infant deaths per 1,000 live births in 1996. Neonatal and postneonatal mortality rates declined for all races combined as well as for postneonatal white infants. Although not statistically significant, mortality rates for white and black neonatal infants and black postneonatal infants also declined. CONCLUSIONS: The overall improvements in general mortality and life expectancy in 1996 continue the long-term downward trend in U.S. mortality. The drop in U.S. infant mortality continues the steady declines of the past four decades.

Deaths: final data for 1999.

OBJECTIVES: This report presents final 1999 data on U.S. deaths and death rates according to demographic and medical characteristics. Trends and patterns in general mortality, life expectancy, and infant and maternal mortality are also described. A previous report presented preliminary mortality data for 1999. METHODS: In 1999 a total of 2,391,399 deaths were reported in the United States. This report presents tabulations of information reported on the death certificates completed by funeral directors, attending physicians, medical examiners, and coroners. Original records are filed in the State registration offices. Statistical information is compiled into a national data base through the Vital Statistics Cooperative Program of the National Center for Health Statistics (NCHS), Centers for Disease Control and Prevention. For the first time in a final mortality data report, age-adjusted death rates are based upon the year 2000 population and causes of death are processed in accordance with the Tenth Revision of the International Classification of Diseases (ICD-10). RESULTS: The 1999 age-adjusted death rate for the United States was 881.9 deaths per 100,000 standard population, a 0.7 percent increase from the 1998 rate, and life expectancy at birth remained the same at 76.7 years. For all causes of death, age-specific death rates rose for those 45-54 years, 75-84 years, and 85 years and over and declined for a number of age groups including those 5-14 years, 55-64 years, and 65-74 years. Aortic aneurysm and dissection made its debut in the list of leading causes of death and atherosclerosis exited from the list. Heart disease and cancer continued to be the leading and second leading causes of death. The age-adjusted death rate for firearm injuries decreased for the sixth consecutive year, declining 6.2 percent between 1998 and 1999. The infant mortality rate, 7.1 infant deaths per 1,000 live births, was not statistically different from the rate in 1998. CONCLUSIONS: Generally, mortality continued long-term trends. Life expectancy in 1999 was unchanged from 1998 despite a slight increase in the age-adjusted death rate from the record low achieved in 1998. Although statistically unchanged from 1998, the trend in infant mortality has been of a steady but slowing decline. Some mortality measures for women and persons 85 years and over worsened between 1998 and 1999.