The hepatic immune system

The liver regulates T-cell homeostasis, induces T-cell tolerance, and supports intrahepatic T-cell responses against hepatotropic pathogens. Many data from clinical and preclinical systems provide supportive evidence for these diverse roles of the liver in modulating peripheral (systemic, mucosal, and intrahepatic) T-cell immunity. Little information is available on the cellular and molecular mechanisms that mediate the dual role of the liver in tolerizing T-cell responses and in supporting intrahepatic priming of T-cell responses. Understanding these immunoregulatory effects in the liver may offer insight into clinically relevant immunopathologies of this organ.     

Die Ausbildung der Haptoglobintypen im Säuglingsalter

Zusammenfassung Das gesunde Neugeborene bildet seinen eigenen Haptoglobintyp innerhalb der 1. Lebenswoche aus. Unreife (Frühgeborene) und starke Hämolyse können das Auftreten verzögern. Am Ende des 3. Monats war der eigene Typ bei allen untersuchten Säuglingen (865) nachweisbar.     

Über Schwankungen von Fermentaktivitäten in der Leber bei experimentellen Eingriffen und bei Infektionskrankheiten

Ohne ZusammenfassungAn dieser Stelle sei der Deutschen Forschungsgemeinschaft, mit deren Hilfe die Arbeiten zum Teil durchgeführt wurden, gedankt.     

Rezidivierende Meningitis bei familiärem Mangel der achten Komponente des Komplementsystems

Summary An 18-year-old man suffered from recurrent bacterial meningitis. Investigation of the complement system revealed deficiency of the 8th complement component (C8) in the patient and his sister. Genetic defects of the terminal complement components C5 to C8 predispose toNeisseria infections, probably due to a lack in bacteriolytic activity. It is to be noted that 1 year ago the patient had been hospitalized for a culture-proved pneumococcal meningitis.

     

Search for intracranial aneurysm susceptibility gene(s) using Finnish families

Background

Cerebrovascular disease is the third leading cause of death in the United States, and about one-fourth of cerebrovascular deaths are attributed to ruptured intracranial aneurysms (IA). Epidemiological evidence suggests that IAs cluster in families, and are therefore probably genetic. Identification of individuals at risk for developing IAs by genetic tests will allow concentration of diagnostic imaging on high-risk individuals. We used model-free linkage analysis based on allele sharing with a two-stage design for a genome-wide scan to identify chromosomal regions that may harbor IA loci.

Methods

We previously estimated sibling relative risk in the Finnish population at between 9 and 16, and proceeded with a genome-wide scan for loci predisposing to IA. In 85 Finnish families with two or more affected members, 48 affected sibling pairs (ASPs) were available for our genetic study. Power calculations indicated that 48 ASPs were adequate to identify chromosomal regions likely to harbor predisposing genes and that a liberal stage I lod score threshold of 0.8 provided a reasonable balance between detection of false positive regions and failure to detect real loci with moderate effect.

Results

Seven chromosomal regions exceeded the stage I lod score threshold of 0.8 and five exceeded 1.0. The most significant region, on chromosome 19q, had a maximum multipoint lod score (MLS) of 2.6.

Conclusions

Our study provides evidence for the locations of genes predisposing to IA. Further studies are necessary to elucidate the genes and their role in the pathophysiology of IA, and to design genetic tests.     

Low plasma glutamine in combination with high glutamate levels indicate risk for loss of body cell mass in healthy individuals: the effect of N-acetyl-cysteine

Skeletal muscle catabolism, low plasma glutamine, and high venous glutamate levels are common among patients with cancer or human immunodeficiency virus infection. In addition, a high glycolytic activity is commonly found in muscle tissue of cachectic cancer patients, suggesting insufficient mitochondrial energy metabolism. We therefore investigated (a) whether an anaerobic physical exercise program causes similar changes in plasma amino acid levels, and (b) whether low plasma glutamine or high glutamate levels are risk factors for loss of body cell mass (BCM) in healthy human subjects, i.e., in the absence of a tumor or virus infection. Longitudinal measurements from healthy subjects over longer periods suggest that the age-related loss of BCM occur mainly during episodes with high venous glutamate levels, indicative of decreased muscular transport activity for glutamate. A significant increase in venous glutamate levels from 25 to about 40 M was seen after a program of anaerobic physical exercise. This was associated with changes in T lymphocyte numbers. Under these conditions persons with low baseline levels of plasma glutamine, arginine, and cystine levels also showed a loss of BCM. This loss of BCM was correlated not only with the amino acid levels at baseline examination, but also with an increase in plasma glutamine, arginine, and cystine levels during the observation period, suggesting that a loss of BCM in healthy individuals terminates itself by adjusting these amino acids to higher levels that stabilize BCM. To test a possible regulatory role of cysteine in this context we determined the effect of N-acetyl-cysteine on BCM in a group of subjects with relatively low glutamine levels. The placebo group of this study showed a loss of BCM and an increase in body fat, suggesting that body protein had been converted into other forms of chemical energy. The decrease in mean BCM/body fat ratios was prevented by N-acetyl-cysteine, indicating that cysteine indeed plays a regulatory role in the physiological control of BCM.Abbreviations BCM Body cell mass - HIV Human immunodeficiency virus type 1 - NAC N-Acetyl-cysteine     

Inhibition of nitric oxide synthase reduces Sephadex-induced oedema formation in the rat lung: Dependence on intact adrenal function

In the present study we have investigated the effect of L-nitro arginine mono methyl ester (L-NAME), an inhibitor of nitric oxide (NO) synthase on Sephadex induced inflammation in the rat lung. Instillation of Sephadex into the airways induced an inflammatory reaction characterized by a long-lasting interstitial oedema, measured as an increase in lung weight, and an influx of inflammatory cells into the airways. L-NAME given s.c. prevented the increase in lung weight following Sephadex instillation. The inactive enantiomer D-NAME had no effect, nor did aminoguanidine which indicates that this effect of L-NAME was mediated by inhibition of the constitutive form of NOS. Treatment with L-NAME did not reduce an established oedema. In contrast, L-NAME tended to enhance the influx of oesinophils into the airways of Sephadex-instilled animals.L-NAME did not have any effect on the development of oedema in adrenalectomized rats or in animals where formation of glucocorticosteroids (GCS) was inhibited with metyrapone. L-NAME did not however, increase plasma levels of corticosterone. The present results indicate that, in this model, inhibition of NO-synthesis has marked anti-inflammatory effects. The underlying mechanism is complex but seems not to involve prevention of overproduction of NO.