GARP inhibits allergic airway inflammation in a humanized mouse model.

BACKGROUND: Regulatory T cells (Treg) represent a promising target for novel treatment strategies in patients with inflammatory/allergic diseases. A soluble derivate of the Treg surface molecule glycoprotein A repetitions predominant (sGARP) has strong anti-inflammatory and regulatory effects on human cells in vitro as well as in vivo through de novo induction of peripheral Treg. The aim of this study was to investigate the immunomodulatory function of sGARP and its possible role as a new therapeutic option in allergic diseases using a humanized mouse model. METHODS: To analyze the therapeutic effects of sGARP, adult NOD/Scidγc(-/-) (NSG) mice received peripheral blood mononuclear cells (PBMC) derived from allergic patients with sensitization against birch allergen. Subsequently, allergic inflammation was induced in the presence of Treg alone or in combination with sGARP. RESULTS: In comparison with mice that received Treg alone, additional treatment with sGARP reduced airway hyperresponsiveness (AHR), influx of neutrophils and macrophages into the bronchoalveolar lavage (BAL), and human CD45(+) cells in the lungs. Furthermore, the numbers of mucus-producing goblet cells and inflammatory cell infiltrates were reduced. To elucidate whether the mechanism of action of sGARP involves the TGF-ß receptor pathway, mice additionally received anti-TGF-ß receptor II (TGF-ßRII) antibodies. Blocking the signaling of TGF-ß through TGF-ßRII abrogated the anti-inflammatory effects of sGARP, confirming its essential role in inhibiting the allergic inflammation. CONCLUSION: Induction of peripheral tolerance via sGARP is a promising potential approach to treat allergic airway diseases.

[Remarks on finding "real" sexual differential values--presented by the example of measurements of vital capacity (author's transl)]. / Bemerkungen zur Ermittlung "realer" Sexualdifferenzwerte, dargestellt am Beispiel von Messungen zur Vitalkapazität.

Investigations conducted over many years have lead to the proposal to use - on the basis of classes of equal stature - the "female-male-index" (Ifm) for anthropometric, physiological and physical-athletic measured or performance values, respectively, which correlate significantly with stature. A "standard table for measurements of vital capacity by dry spirometer" is used to present this method of applying the "real" sexual differential values.

The value of morphological prognostic criteria in the assessment of renal cell carcinoma.

In this study, we examined some of the morphological values from the large number of prognostic parameters indicated in the literature by establishing survival statistics. Primary distant metastasis formation was confirmed to be a prognostically unfavorable factor. Regional metastasis formation takes an intermediate position between the primarily distantly metastasized and the primary non-metastasized renal cell carcinoma. In the primarily non-metastasized renal cell carcinoma, tumor invasion into the renal vein is associated with prognostic deterioration, obviously due to a linkage to other unfavorable tumor characteristics. The histological degree of malignancy as a single prognostic parameter seems to be of little informational value if no other tumor data are taken into consideration. The classification of renal tumors according to Robson proves to be of great clinical relevance, especially when it is combined with the histological degree of malignancy. The prognostic scheme by Hermanek 'combined staging and grading' must be recommended as the prognostic scheme of choice. Apart from special histological types of the renal cell carcinoma, such as the papillary or sarcomatous variant, and with reservation as to the tendency to unpredictable secondary metastasis formation that is peculiar to the renal cell carcinoma, a prediction of the prognosis according to the morphological criteria mentioned above is possible to a satisfactory degree within certain limits.

More exercise for the hyperlipidaemic patients?

Epidemiological studies have left no doubt that moderate to vigorous physical training (PT) of endurance type decreases atherogenic lipoprotein fractions and increases vasoprotective lipoproteins. Depending on the underlying metabolic abnormality in various dyslipoproteinaemias a different response to endurance training was observed. PT is particularly effective in most forms of primary hypertriglyceridaemias. PT acts on both excessive VLDL production and fractional catabolic rate of TG--rich lipoproteins. However, improved removal seems to be of dominating importance. In primary hypercholesterolaemia LDL--cholesterol levels did not change during a 4 weeks exercise regimen with standardized isocaloric lipid lowering diet. In observational studies with hyperlipidaemic patients with stable body weight and under lipid lowering diet, during the first 4-6 weeks no significant effect on HDL was seen, whereas longterm studies clearly demonstrate an increase in HDL--cholesterol. Further beneficial effects of PT in hyperlipidaemic patients are improved glucose tolerance, down--regulation of hyperinsulinaemia, lowering of blood pressure and correction of hypercoagulability of the blood.

[Physiologic studies of maturity diagnosis in the calf and its relationship to the postnatal condition]. / Physiologische Untersuchungen zur Reifediagnostik beim Kalb und ihre Beziehungen zum postnatalen Zustand.

The parameters of kidney, lung, and skin maturity, known from human medicine, were for the first time determined from amniotic fluid of cattle. Given the difference in placentation, it is not known whether the conditions of the human fetus can be fully applied to the bovine fetus, the detectability of such maturity criteria may be indicative of comparable morphokinetic conditions in the bovine fetus. All physiological parameters investigated exhibited difference to the benefit of surviving calves. Positive correlations were found to exist between the lecithin/sphingomyelin quotient and body weight gain in the first week of age as well as drinking behaviour of the calves. Hence, insufficient concentration of surface-active phospholipids in calf breeding has measurable effects on quantitatively definable characteristics.

Surgery of the primary tumor of metastasizing renal carcinoma.

40% or 116 of 350 patients with renal carcinoma had distant metastases at the time of hospital admission (M1, N0-4). Women fell ill less often than men did (3:7). 82 of 116 patients (71%) received nephrectomy primarily. Lethality within the first 30 days was 6%. Patients with nephrectomy survived longer than those without, women with nephrectomy survived longer than men. Patients with a grade II tumor survived longer than those with a grade III tumor. Palliative nephrectomy can therefore be recommended as treatment of choice, if the general condition of the patient allows it, the more so as there are no alternative ways of treatment.

[Pathogen spectrum of urethritis in the man]. / Erregerspektrum der Urethritis des Mannes.

545 male patients with a tentative diagnosis "urethritis" were examined between November 1984 and December 1994 in the Department of Dermatology and Venerology of the Military Hospital in Ulm. The patients, aged from 18 to 58 years (mean age 24.1 years), were examined according to a standardized diagnostic procedure: Smear preparations from the urethra with subsequent gram staining, bacterial cultures for aerobic bacteria, Neisseria gonorrhoeae (cultures and Phadebact gonococcus test), mycoplasma cultures (Mycoplasma hominis (M. hom.); Ureaplasma urealyticum (U. u), and Chlamydia trachomatis using several methods, primarily DIFT (Syva Micro-Trak). Trichomonas vaginalis counts in urine sediment 441 patients (81%) had 4 or more leukocytes per high-power (x1000) field in the gram stained specimens. In these 441 urethritis-patients the following germs could be detected: Trichomonas vagin 3 (1%), N. gonorrhoeae 80 (18%), Mycoplasma 94 (21%) [U. u. 59, M. hom. 24, both 11], C. trachomatis 114 (26%), other pathogenic bacteria 135 (31%). In 114 patients (26%) no bacteria could be identified. A single infection was diagnosed in a total of 242 patients (55%), a double infection was determined in 71 patients (16%) while a triple infection was found in 14 patients (3%). The spectrum determined in the single infection included the following: N. gonorrhoeae 41 (9%), Mycoplasma 45 (10%), C. trachomatis 67 (15%), other pathogenic bacteria 89 (20%) (most frequently found germs were Enterococcus, beta-hemolytic Streptococcus, Escherichia coli, Staph. aureus). In the double infections combinations with aerobic bacteria dominated. In triple infections, mycoplasma were most common. During the investigation period the number of patients with urethritis symptoms declined at a constant rate.

[Results of protein-sparing modified fasting in hyperlipoproteinemias]. / Ergebnisse des proteinsparenden modifizierten Fastens bei Hyperlipoproteinämien.

We investigated the influence of a PSMF on body weight, body composition, blood lipids, physical working capacity, and nitrogen balance in obese HLP patients. During 4 weeks, 12 patients were treated by PSMF (approximately 340 kcal/d) under health resort conditions. At the same time, they daily exercised on a bicycle with an intensity of 80% of their physical working capacity estimated by an exercise load. The therapeutic regimen induced a significant weight loss (10.1 kg in the mean). Evidently, the patients diminished their body fat only as could be shown by estimations of total body water. Triglycerides, total cholesterol, and LDL-cholesterol also decreased significantly, while HDL-cholesterol remained unchanged. In spite of the weight reduction, the physical working capacity significantly increased from 57.8 to 93.2 kgm. Measurements of total nitrogen excretion with urine gave evidence of the protein saving effect of the therapy. Thus, PSMF--representing an effective therapeutic procedure--can be recommended to be used in obese HLP patients, proceeded that contraindications have been taken into consideration carefully.