Phagocyte function and cytokine production in community acquired pneumonia.

BACKGROUND--It is possible that many deaths from pneumonia may involve the generation of inflammatory mediators and tissue damage by activated phagocytes. To test this hypothesis phagocyte function, plasma levels of interleukin 6 (IL-6), tumour necrosis factor alpha (TNF alpha), and soluble interleukin 2 receptor (IL-2R), disease severity, and outcome have been examined in 46 patients with community acquired pneumonia. METHODS--Polymorphonuclear leucocyte (PMNL) and monocyte function were measured daily by chemiluminescence in these patients during the first week of admission, and cytokine levels were subsequently determined by ELISA. A series of 61 healthy individuals were used as a control group for the chemiluminescence results. RESULTS--There was evidence of phagocyte, particularly PMNL, activation on admission in 76% of the patients. Most patients (86%) also had raised IL-2R levels on admission. IL-6 and unbound TNF alpha were present in 23% and 41% of patients at varying times during the course of the disease. There was little correlation between measurements of cytokine or phagocyte levels and outcome or indicators of disease severity, although this may be because of the small number of patients included in this preliminary study. CONCLUSIONS--These results are consistent with the hypothesis that activated phagocyte function and raised levels of circulating cytokines may contribute to the pathogenesis of community acquired pneumonia. There are striking similarities in this respect between pneumonia, adult respiratory distress syndrome, and sepsis.     

A New Derived and Highly Polymorphic Chromosomal Race of Liolaemus Monticola (Iguanidae) from the 'Norte Chico' of Chile

A multiple Robertsonian fission chromosomal race of the Liolaemus monticola complex in Chile is described and is shown to be the most derived and the most complex among the Liolaemus examined thus far. The 29 karyotyped lizards analysed from the locality of Mina Hierro Viejo, Petorca, Provincia de ValparaUso, Chile, exhibited a diploid chromosomal number ranging from 42 to 44, and several polymorphisms. The polymorphisms included: a pair 1 fission; a pair 2 fission plus a pericentric inversion in one of the fission products, which moved the NOR and satellite from the tip of the long arm of the metacentric 2 to the short arm of the fission product; a fission in pair 3; a polymorphism for an enlarged chromosome pair 6; and a polymorphism for a pericentric inversion in pair 7. This population is fixed for a fission of chromosome pair 4. A total of 76% of the lizards analysed were polymorphic for one or more pairs of chromosomes. We have compared these data with other Liolaemus monticola chromosomal races and calculated the Hardy–Weinberg ratios for the polymorphic chromosome pairs in this Multiple-Fission race. Karyotypic differences between the Northern (2n = 38–40) and the Multiple-Fission (2n = 42–44) races were attributed mainly to Robertsonian fissions, an enlarged chromosome and pericentric inversions involving the macrochromosomes and one microchromosome pair.     

Racial differences in the incidence of end-stage renal disease in types I and II diabetes mellitus

An increased risk of end-stage renal disease (ESRD) among blacks has been previously shown for most causes of chronic renal failure, including diabetes. Most previous studies have not considered the higher prevalence of diabetes in the black population and have not analyzed relative risk by type of diabetes. We found that the incidence of ESRD among blacks with diabetes was 3.6 times the rate in whites with diabetes. The relative risk for blacks increases progressively with age, reaching a maximum of 6.9 in persons over the age of 65. The incidence of ESRD due to diabetes is higher in the population with type I diabetes (492 per 100,000) than in the population with type II diabetes (71 per 100,000). Blacks have a higher incidence of ESRD in both type I diabetes (odds ratio, 2.96; 95% confidence interval, 1.8 to 4.9) and type II diabetes (odds ratio, 4.9; 95% confidence interval, 3.6 to 6.5). The incidence of ESRD in patients with diabetes varies with age, race, and type of diabetes.     

Cystinuria and its treatment: 25 years experience at St. Bartholomew's hospital

Summary Cystinuria is an inherited condition affecting the active transport of the diamino acids cystine, ornithine, lysine and arginine across the renal tubule and the small intestine. The only clinical effect is the production of urinary tract stones and if these can be prevented the affected individuals can lead a normal life. In many people cystine stones can be dissolved and new stone formation prevented by a high fluid intake, but if this does not succeed regular treatment with penicillamine will do so. Although many side-effects have been described with penicillamine treatment it is rare for them to be severe enough to prevent its use in patients with cystinuria. Since the clinical effects of cystinuria can be prevented by either a high fluid intake or by penicillamine it is important to make the diagnosis in affected individuals as soon as possible and cystinuria should therefore be considered in all people (regardless of age) who form urinary stones.     

Neuropathogenesis of Chimeric Simian/Human Immunodeficiency Virus infection In Pig-tailed and Rhesus Macaques

We recently reported that a chimeric simian/human immunodeficiency virus (SHIV_KU-1) developed in our laboratory caused progressive depletion of CD4⁺T lymphocytes and AIDS within 6 months of inoculation into pig-tailed macaques (M.nemestrina). None of the pig-tailed macaques showed productive SHIV infection in the central nervous system (CNS). In this report, we show that by further passage of the pathogenic virus in rhesus macaques [M. mulatta], we have derived a new strain of SHIV (SHIV_KU-2) that has caused AIDS and productive CNS infection in 3 of 5 rhesus macaques infected with the virus. Productive replication of SHIV in the CNS was clearly shown by high infectivity titers and p27 protein levels in brain homogenates, and in 2 of the 3 rhesus macaques this was associated with disseminated, nodular, demyelinating lesions, including focal multinucleated giant cell reaction, largely confined to the white matter. These findings were reminiscent of HIV-1 associated neurological disease, and our immunohistochemical and in situ hybridization data indicated that the neuropathological lesions were associated with the presence of SHIV-specific viral antigens and nucleic acid respectively. However, the concomitant reactivation of opportunistic infections in these macaques suggested that such pathogens may have influenced the replication of SHIV in the CNS, or modified the neuropathological sequelae of SHIV infection in the rhesus species, but not in pig-tailed macaques. Our findings in the two species of macaques highlight the complexities of lentiviral neuropathogenesis, the precise mechanisms of which are still elusive.     

Transformation of alveolar type 2 cells to type 1 cells following exposure to NO2.

This research was undertaken to study the fate of Type 2 cells after they have divided. To accomplish this, male rats were exposed to NO₂ to increase the number of dividing Type 2 cells. Dividing cells were labeled with ³H-TdR and studied with autoradiographic techniques in the electron microscope for up to 14 days after labeling. The results show that initially most of the ³H-TdR labeled cells were Type 2. However, by 2 days there was a decrease in frequency of labeled Type 2 cells and a large increase in labeled Type 1 cells. The new frequencies of labeled alveolar epithelial cells were stable from 2 through 14 days. This evidence supports the interpretation that Type 2 cells may transform into Type 1 cells. In addition, it was shown that under the conditions of this experiment: (1) the time for transformation was about 2 days, and (2) during this process an intermediate cell type was present.