Similarities and differences of human and experimental mouse lymphangiomas.

Lymphangioma is a disfiguring malformation of early childhood. A mouse lymphangioma model has been established by injecting Freund's incomplete adjuvant (FIA) intraperitoneally, but has not been compared with the human disease. We show that, in accordance with studies from the 1960s, the mouse model represents an oil-granuloma, made up of CD45-positive leukocytes and invaded by blood and lymph vessels. Several markers of lymphatic endothelial cells are expressed in both mouse and human, like CD31, Prox1, podoplanin, and Lyve-1. However, the human disease affects all parts of the lymphovascular tree. We observed convolutes of lymphatic capillaries, irregularly formed collectors with signs of disintegration, and large lymph cysts. We observed VEGFR-2 and -3 expression in both blood vessels and lymphatics of the patients, whereas in mouse VEGFR-2 was confined to activated blood vessels. The experimental mouse FIA model represents a vascularized oil-granuloma rather than a lymphangioma and reflects the complexity of human lymphangioma only partially.     

Mouse hepatitis virus nucleocapsid protein-specific cytotoxic T lymphocytes are Ld restricted and specific for the carboxy terminus.

Infection of mice with the JHM strain of mouse hepatitis virus (MHV) results in an acute encephalomyelitis associated with primary demyelination of the central nervous system. Efforts at understanding the components of the immune response in the development of chronic MHV-induced demyelination have implicated the antibody response and both the CD4+ and CD8+ T cell responses. In this report, we demonstrate that Balb/c (H-2d) mice immunized with the JHM (JHMV) strain of MHV develop a CD8+ cytotoxic T lymphocyte (CTL) response. One population of these virus-specific CTL recognize the nucleocapsid (N) protein. Recombinant vaccinia viruses expressing either the entire N protein or carboxy-terminal deletions were used to determine the number and location of the epitope(s) recognized. The CTLs were found to recognize a peptide contained within the carboxy-terminal 149 amino acids of the N protein. Analysis of infected cell lines expressing transfected major histocompatibility genes demonstrated that the anti-N protein CTLs were restricted exclusively to the Ld molecule. These data provide the first definition of a MHV-specific CTL response directed to a viral protein and suggest that the anti-N protein CTL response is one potential mechanism used by the host to clear JHMV from the central nervous system.     

EEG delta power during sleep in young and old rats

Delta EEG power density, which has been viewed as a measure of intensity of NREM sleep, declines across the lifetime in humans, cats, and hamsters, but data in rats have been unclear. It is also uncertain whether older rats differ from younger animals in the degree of change in delta power during recovery sleep following short-term sleep deprivation. We have examined delta power density in NREM sleep under baseline conditions and following 48 h of sleep deprivation in young (3 months), middle-aged (12 months), and older (24 months) rats. The presence or absence of age effects was highly dependent on the method of normalizing the data. When expressed as a fraction of total NREM EEG power, there was no age effect on baseline delta power density, or on the change from baseline to recovery conditions. When expressed as a multiple of delta power in REM under the same condition, the younger rats had higher delta power density than the middle-aged and older rats. For all the ages combined, there was an increase in delta power density in the recovery condition. When examined by age, the younger rats (which started from a higher level of delta power density than the other groups) did not have an increase in delta during recovery; the middle-aged rats tended to, and the older rats (which started from lower baseline levels) significantly increased delta power density in the recovery condition. This suggests that the lower delta power seen during baseline in older rats is not due to decreased ability to generate delta activity.     

Der Nachweis tubulärer Funktionsstörungen der Niere durch Bestimmung der Aminopeptidase-Aktivität im Harn

Zusammenfassung Aminopeptidase findet sich im lumennahen Cytoplasma der Zellen des proximalen Tubulus der Niere in hoher Konzentration. Bei Schädigungen der Tubuluszellen, die mit einer Änderung der Permeabilität der Zellmembranen einhergehen, kann sie in den Harn übertreten. Dementsprechend ist bei akuten Läsionen des proximalen Tubulus eine erhöhte Aminopeptidase-Aktivität im Harn zu erwarten.An einer Reihe von Beispielen sollte gezeigt werden, daß die Bestimmung der Aminopeptidase-Aktivität im Harn zum Nachweis akuter Funktionsstörungen des proximalen Tubulus geeignet ist.

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Summary Aminopeptidase occurs in high concentration in the luminal portion of the cytoplasma of cells of the proximal convoluted tubules. In case of damage of the tubular cells this enzyme can pass into the urine. Thus, in acute lesions of the proximale tubule an elevated aminopeptidase activity in the urin is to be expected.The task was to demonstrate in a series of cases, that the determination of the aminopeptidase activity in the urine serves for the evaluation of acute disturbances of the proximal tubule.

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Als Aminopeptidase (sog. Leucin-Aminopeptidase, LAP), bezeichnen wir in der vorliegenden Arbeit dasjenige Enzym oder diejenigen Enzyme, die in der Lage sind,l-Leucyl--Naphthylamid zu spalten.     

Seroepidemiology of HTLV-III (LAV) in the Federal Republic of Germany

Summary In 1984 10,281 sera were collected in the FRG and examined for antibodies to HTLV-III (LAV) with an enzyme-linked immunosorbent assay and confirmative tests. Of the German AIDS patients 81% have antibodies. Individuals belonging to AIDS risk groups, homosexuals, haemophiliacs and i.v. drug abusers, have antibody frequencies between 25%–72%. The detection of HTLV-III antibodies in blood donours indicates that the virus is being transmitted by blood transfusions.Abbreviations AIDS acquired immunodeficiency syndrome - LAS lymphadenopathy syndrome - ARC AIDS related complex - LAV lymphadenopathy associated virus - HTLV-III human T-lymphotropic virus type III - HBV hepatitis B virus     

TrkC Is Essential for Nephron Function and Trans-Activates Igf1R Signaling

BackgroundInjury to kidney podocytes often results in chronic glomerular disease and consecutive nephron malfunction. For most glomerular diseases, targeted therapies are lacking. Thus, it is important to identify novel signaling pathways contributing to glomerular disease. Neurotrophic tyrosine kinase receptor 3 (TrkC) is expressed in podocytes and the protein transmits signals to the podocyte actin cytoskeleton.MethodsNephron-specific TrkC knockout (TrkC-KO) and nephron-specific TrkC-overexpressing (TrkC-OE) mice were generated to dissect the role of TrkC in nephron development and maintenance.ResultsBoth TrkC-KO and TrkC-OE mice exhibited enlarged glomeruli, mesangial proliferation, basement membrane thickening, albuminuria, podocyte loss, and aspects of FSGS during aging. Igf1 receptor (Igf1R)–associated gene expression was dysregulated in TrkC-KO mouse glomeruli. Phosphoproteins associated with insulin, erb-b2 receptor tyrosine kinase (Erbb), and Toll-like receptor signaling were enriched in lysates of podocytes treated with the TrkC ligand neurotrophin-3 (Nt-3). Activation of TrkC by Nt-3 resulted in phosphorylation of the Igf1R on activating tyrosine residues in podocytes. Igf1R phosphorylation was increased in TrkC-OE mouse kidneys while it was decreased in TrkC-KO kidneys. Furthermore, TrkC expression was elevated in glomerular tissue of patients with diabetic kidney disease compared with control glomerular tissue.ConclusionsOur results show that TrkC is essential for maintaining glomerular integrity. Furthermore, TrkC modulates Igf-related signaling in podocytes.     

Induction of inflammatory mediator release (serotonin and 12-hydroxyeicosatetraenoic acid) from human platelets by Pseudomonas aeruginosa glycolipid.

Purified glycolipid from Pseudomonas aeruginosa induced the generation of significant amounts of 12-hydroxyeicosatetraenoic acid (12-HETE) and serotonin release from human platelets. The release of serotonin was first observed 2 min after addition of the glycolipid and increased with time. Significant serotonin release was obtained at glycolipid concentrations above 5 micrograms/ml and increased dose-dependently up to 100% at glycolipid concentrations above 40 micrograms/ml. Glycolipid induced 12-HETE in a time- and dose-dependent manner. 12-HETE formation was first measured after 10 min of incubation and increased with time. Optimal 12-HETE formation was obtained at a glycolipid concentration of 50 micrograms/ml; higher concentrations of glycolipid led to a decrease in 12-HETE formation, indicating a cytotoxic effect. Stimulation of platelets with glycolipid (12-HETE formation and serotonin release) was accompanied by calcium influx, translocation of protein kinase C, activation of guanylylimidodiphosphate binding, and increased GTPase activity in platelet membranes within the same concentration range.     

Regional organisational audit of district departments of public health.

Organisational audit of public health in the United Kingdom is rare. To provide a framework for a structured organisational audit in district public health departments in one region organisational factors contributing to efficient, high quality work were identified and compared between districts, enabling each department to identify its organisational strengths and weaknesses. A draft list of organisational factors, based on the King's Fund organisational audit programme, were rated by 52 public health physicians and trainees in 12 district public health departments in South East Thames region for their importance on a scale of 0 (not relevant) to 5 (vital). Factors with average ratings of > 4, judged to be "vital" and proxies for standards, were then used to compare each district's actual performance, as reported by its director of public health in a self reported questionnaire. In all, 37 responses were received to the rating questionnaire (response rate 71%) and 12 responses to the directors' questionnaire. Of the 54 factors identified as vital factors, 20(37%) were achieved in all 12 districts and 16(30%) in all but one district; 18 were not being achieved by two (33%) districts or more. Overall, vital factors were not being achieved in 9% of cases. The authors concluded that most departments are achieving most vital organisational factors most of the time, but improvement is still possible. The results have been used as a basis for planning the organisation of public health departments in several of the newly formed commissioning agencies. This was the first regional audit of public health of its kind performed in the region and it provided valuable experience for planning future regional audit activity.