Antibodies in guinea-pigs immunized with kidney and lung basement membranes

The cross-reaction of antibodies to tubular basement membrane (TBM) with alveolar basement membrane (ABM) has been studied in guinea-pigs with tubulointerstitial (TI) nephritis. Forty-three of fifty-two Hartley guinea-pigs immunized with rabbit TBM in complete Freund's adjuvant developed TI nephritis. In addition to linear deposits of guinea-pig IgG and C3 in the TBM, thirty-two of the nephritic animals showed linear immune deposits in ABM; twelve of these animals had thickened alveolar septa and increased numbers of polymorphonuclear (PMN) leucocytes in lung tissue. Sera and eluates of kidney and lung from nephritic guinea-pigs reacted strongly with TBM and more weakly with ABM of normal animals. Absorption experiments suggested that antibodies to TBM and ABM were closely related or identical. Only a minority of guinea pigs immunized with TBM showed in vivo binding of IgG to glomerular basement membrane (GBM). Immunization of guinea-pigs with lung-homogenate-induced antibodies binding to TBM and ABM (in approximately 45% of animals) and to GBM (in approximately 30% of animals). Immunization with crude GBM-induced antibodies which reacted preferentially with TBM and ABM. In contrast, collagenase-treated GBM-induced antibodies preferentially reactive with GBM. TI nephritis was induced in both Strain 13 and Strain 2 guinea-pigs, but the nephropathy developed much faster in Strain 13 animals. Immunization with rabbit TBM-induced antibodies reactive with ABM in 25% of Strain 13 guinea-pigs and in 50% of Strain 2 guinea-pigs, respectively.     

IL-4 inhibits human CD8 T cell expression of the common IL-2 receptor gamma chain

Previous studies in both rats and humans have shown that interleukin (IL) 4 can suppress the generation of IL-2-producing CD8 T cells. In an attempt to elucidate the mechanism by which this suppression is brought about, we set out to investigate whether the IL-4 signal interferes with the IL-2 receptor system. It has already been reported that IL-2 can affect the expression of its own receptor and thus provide a means of controlling its own activities. In this study, we demonstrate that the IL-2 Ralpha- and the IL-2 Rgamma-chains are dramatically upregulated following stimulation of CD8 T cells, whereas lower levels of beta-chain are observed. IL-4 did not affect the expression of the alpha- or beta-chains, but was found to inhibit the generation of common gamma-chain-expressing cells. Moreover, CD4 T cells were found to express much lower levels of this subunit and appeared less sensitive to the effects of IL-4. We postulate that the differential expression of the gamma-chain subunit, in the presence and absence of IL-4, may provide a tool for identifying functionally distinct subpopulations of CD8 T cells.     

Studies on the dispersal of staphylococci

The dispersal of staphylococci during undressing in a cubicle has been investigated. The ability to disperse appears to be largely dependent on the degree of contamination of the skin with staphylococci. There are some major differences in the numbers of bacteria and skin scales disseminated by different groups of people, e.g., patients with skin disease disseminated more than did normal persons. Differences in dissemination between males and females appeared to be largely due to differences in clothing.     

The effect of carbon dioxide in the airways and alveoli on ventilation; a vagal reflex studied in the dog

1. The inhalation of CO(2) produces a tachypnoea only in the presence of intact vagus nerves; the present study was designed to examine the mechanism of this phenomenon in the dog.2. Closed-chest cardiopulmonary bypass was established in dogs weighing 16-24 kg, anaesthetized with chloralose. When the ;bypass' was established pulmonary blood flow ceased, P(A, CO2) was reduced and the respiratory rate slowed. 3-10% CO(2) in O(2) could then be inhaled without change in the level of P(a, CO2) set at the oxygenator.3. The addition of CO(2) in these concentrations to the inspired oxygen resulted in an increase in respiratory frequency, maximal at the first breath and sustained for the 1 min period of exposure. The increase in respiratory frequency was due to a shortening of expiratory duration. Inspiratory duration did not change. The response was absent after vagotomy.4. Inert gases in O(2), given as a control, had no effect on breathing.5. The effect of raising P(a, CO2) (by increasing the concentration of CO(2) in the gas equilibrating the blood in the oxygenator), was primarily to increase tidal volume.6. The ventilatory effect of inspiring CO(2)/O(2) mixtures was shown to be additive to the effect of raising P(a, CO2).7. These experiments show that an afferent vagal reflex originating from the lungs causes tachypnoea, when a dog, on ;bypass', inhales low concentrations of CO(2) in O(2).     

Minimal progesterone support required for the maintenance of pregnancy in mice

A study of the degree of progesterone support required for the maintenance of various stages of pregnancy was undertaken in mice. Mated females were ovariectomized at various stages of pregnancy and progesterone and oestradiol support provided by s.c. Silastic implants with known release characteristics. In the earliest stages of pregnancy (days 1-5), very low concentrations of progesterone (<25% of normal physiological values) were sufficient to maintain pre-implantation stages and allow implantation. In the immediate post-implantation period (days 5-9), the development of implantation sites and decidualization required considerably higher progesterone support. In mid-pregnancy (days 11-14), progesterone alone could not maintain pregnancy unless present in very high amounts; however, the presence of oestradiol during this period lowered the progesterone requirements to well within the physiological range. This effect of oestradiol started on day 11 but required the level of oestradiol support to be kept within strictly defined limits, with high concentrations inducing abortion. Progesterone alone was able to maintain pregnancy from day 15. These results indicate that the minimal progesterone support required for pregnancy in mice varies considerably at different stages of pregnancy and is at least partly modulated by oestradiol.      

Reduced visuospatial performance in children with the D2 dopamine receptor A1 allele

Previous studies suggest a reduced dopaminergic function in subjects with the A1 (minor) allele of the D2 dopamine receptor (DRD2) gene. To explore influences on visuospatial ability as a function of the DRD2 gene, 182 alcohol- and other drug-naive sons (age 10–14) of active alcoholic, recovered alcoholic, and nonalcoholic fathers were administered a visuospatial task (Benton's Judgment of Line Orientation Test) which makes minimal motoric/verbal demands. Visuospatial scores were lower for boys with the A1 allele and for sons of active alcoholics. A1-allele boys made more errors than A2 boys on all 11 of the template lines, with the effect being largest for the rightmost presentations. In contrast, the effect of family history for alcoholism was strongest on both right and left midquadrant presentations. Moreover, separate analyses of the two types of errors produced allele but not family history of alcoholism effects when the two lines were misjudged as farther apart than they actually were and family history but not allele effects where the two lines were misjudged as closer together. These results suggest that polymorphism of the DRD2 gene and family history of alcoholism are dissociable determinants of visuospatial ability and that visuospatial defects previously observed in alcoholics may, in part, be antecedent to their drinking behavior.     

Classification and subtype prediction of adult soft tissue sarcoma by functional genomics

Adult soft tissue sarcomas are a heterogeneous group of tumors, including well-described subtypes by histological and genotypic criteria, and pleomorphic tumors typically characterized by non-recurrent genetic aberrations and karyotypic heterogeneity. The latter pose a diagnostic challenge, even to experienced pathologists. We proposed that gene expression profiling in soft tissue sarcoma would identify a genomic-based classification scheme that is useful in diagnosis. RNA samples from 51 pathologically confirmed cases, representing nine different histological subtypes of adult soft tissue sarcoma, were examined using the Affymetrix U95A GeneChip. Statistical tests were performed on experimental groups identified by cluster analysis, to find discriminating genes that could subsequently be applied in a support vector machine algorithm. Synovial sarcomas, round-cell/myxoid liposarcomas, clear-cell sarcomas and gastrointestinal stromal tumors displayed remarkably distinct and homogenous gene expression profiles. Pleomorphic tumors were heterogeneous. Notably, a subset of malignant fibrous histiocytomas, a controversialhistological subtype, was identified as a distinct genomic group. The support vector machine algorithm supported a genomic basis for diagnosis, with both high sensitivity and specificity. In conclusion, we showed gene expression profiling to be useful in classification and diagnosis, providing insights into pathogenesis and pointing to potential new therapeutic targets of soft tissue sarcoma.     

Comparison of leukocyte count and function in smoking and nonsmoking young men.

Leukocyte function and other hematological measurements were tested in 14 smoking and 13 nonsmoking young men free of intercurrent or chronic diseases. Leukocyte chemotaxis was depressed in smoking subjects when compared to the same subjects abstaining from cigarettes or to the nonsmokers. Smoking did not affect the whole blood bactericidal capacity of leukocytes and serum for Staphyloccus aureus or Klebsiella pneumoniae. Total leukocyte counts, hematocritis, and monocyte counts were higher in the smoking subjects when compared to the nonsmokers.     

Mononuclear cells in glomeruli and cytokines in urine reflect the severity of experimental proliferative immune complex glomerulonephritis.

Immunohistochemical methods were used to investigate the role of macrophages in the progression of proliferative immune complex glomerulonephritis. The mononuclear cell component of glomerular inflammation was analysed in three different stages of chronic serum sickness, each of which was clearly distinguished by criteria of kidney function. Urinary excretion of the macrophage secretory products interleukin-1 and tumour necrosis factor was also evaluated in relation to the functional severity of kidney disease. T lymphocytes and macrophages began to accumulate in glomeruli at the onset of proteinuria, but not before. Urinary excretion of interleukin-1 also began with proteinuria. Proteinuria increased in direct correlation with increases in the number of glomerular macrophages. Development of the most severe stage of glomerulonephritis, characterized by cachexia, declining kidney function, and necrotizing glomerular pathology, was accompanied by the disappearance of T cells from glomeruli and the expression of highly abnormal phenotypes by most macrophages. In addition, there was a switch from urinary excretion of interleukin-1 to excretion of tumour necrosis factor. The progression of proliferative immune complex glomerulonephritis was associated with qualitative as well as quantitative changes in glomerular macrophage populations. Differentiation and/or activation of those glomerular macrophages may have resulted from local T cell-mediated immunoregulation. Measurements of urinary cytokine excretion provided a reliable means of monitoring disease progression. The local action of tumour necrosis factor probably contributed to declining kidney function in the most severe stage of disease.