Treatment of solid tumors should obligatorily be combined with the in vivo codepletion of tumor-protecting, CD8+/HLA-DR(+)-suppressor T cells by alloreactive donor T cells whose preprogrammed cell death allows a high GvL-effect before GvHD can be established. Results of animal experiments, including more than 6000 mice.

The FACS-analysis of diseases as different as cancer, autoimmune disorders and chronic (retro)viral infections, including HIV-infection, shows -at least temporarily- a common feature of lymphocyte hyperactivation, characterized by cellular activation markers (HLA-DR, CD26, CD38, CD69, CD2R and/or CD30), as well as by solubilized membrane structures, such as beta-2m, sICAM-I, sIL-2R/sCD25, sCD8, and by some oversecreted immunocyte products (e.g. neopterin, lysozyme and/or cathepsin D). We tested two potential approaches to down-regulate the pathologically elevated CD8+ and HLA-DR+ T cells: (a) In animal model, we tested the sensibility of these, disease inducing and maintaining T cell subsets to in vitro pretreated (cell death preprogrammed) semi-syngeneic and allogeneic donor T cells in tumor-bearing mice. (b) In the first clinical study, we used a novel combination of FDA-approved drugs which inhibits Ca(2+)-influx and concomitantly down-regulates cytosolic cAMP in patient's overstimulated immunocompetent cells. We could achieve a 94.6-100% long-term survival in tumor-bearing mice. In patients, large primary tumors and large metastases shrinked by 80-85% and small metastases disappeared completely. Since in HIV-infected persons, the increased number of HLA-DR+ CD38+T (T8) cells is associated with a fall in CD4-level and with development of AIDS, we are looking for the elimination of these HLA-DR+ targets by our novel technique in two AIDS-simulating (FIV/FeLV and SIV) animal models.

[Novel immunotherapeutic models for neoplastic diseases of the urogenital tract with special attention to bladder carcinoma]. / Neuartige immuntherapeutische Modelle bei neoplastischen Erkrankungen des Urogenitaltraktes unter besonderer Berücksichtigung des Blasenkarzinoms.

In this review article some novel immunotherapeutic models as well as some new concepts concerning the unspecific and specific T-cell stimulation are discussed briefly. Some of these immunotherapeutic models are restricted to bladder cancer; the others have a generalized meaning. One model, restricted to bladder cancer, is based on the enzymatic++ pretreatment of effector-cells (macrophages, NK-cells), followed by their instillation in the patient's bladder. The other bladder tumor restricted model includes the direct in situ activation of effector cells by proteases and lipases. A third model for the treatment of bladder tumor implies a presensitization of patient's TD/TDTH-cells, followed by the treatment of patient's bladder tumor cells by some, common haptenic group. In addition, some novel ways of immune stimulation, partly by circumventing the (tumor-specific) immune tolerance, based on the cross-linking of crucial membrane structures on T4- and T8-cells or on a managed, controlled APC: T-cell interaction, are discussed. The details inclusively the comprehensive special literature can not be brought in this review article; they should be dealt with in special papers being in preparation.

Some acid-base balance-dependent urinary parameters and calcium-binding anions in stone formers.

Urinary organic acids were determined by gradual titration of portioned urine samples of moderately and severely recurrent stone patients and compared to those found in healthy controls. An essential deficit of organic acids was found in patients with a high recurrence rate. According to the results, the lack of organic acids in the urine of urolithiasis patients, accompanied by a reduced inhibition of the calcium-oxalate and calcium-phosphate crystallization might be causatively involved in the stone formation.

[Search for a new rinsing solution for the local lysis of calcium-containing urinary calculi]. / Suche nach neuen Spüllösungen für die lokale Lyse von Ca-haltigen Harnsteinen.

Due to improved rinsing techniques local chemolitholysis is again becoming more important. Good result good results in the local chemolysis of phosphate calculi (calculi caused by remains of Struvit) with Renacidin and other rinsing solutions (Fam, Rossier, Gittes, Jacobs, Smith, Royle, Nemoy, Stamey) have led to a revival chemolitholysis (Alken) in the last 4--5 years, however only in the case of phosphate calculi, which account for 60--80%, cannot be dissolved by Renacidin, as is explicitly pointed out by the manufacturer. The experiments carried out by the group headed by Kallistratos and Timmermann in the 60's using rinsing solutions based on EDTA were discontinued, probably because of physiological reservations concerning the chemicals used and the long duration of treatment at physiologically tolerable concentrations and pH values. In order to extend the range of rinsing solutions to be tested, we tested new substances, including some which complex not only the anion (oxalate) but also the cation (Ca). Alternating treatment with oxalate binding and Ca binding rinsing solutions has been found to give particularly good results.

[Contribution to the problem of preventing recurrences of oxalate and phosphate urinary caluli: active modification of citrate excretion and Ca++-binding capacity in the urine of Wistar rats]. / Beitrag zum Problem der Rezidivprophylaxe von Oxalat- und Phosphatharnsteinen: Aktive Beeinflussung der Zitratausschidung und der Ca++-bindungs-kapazität im Harn bei Wistarratten.

Citric acid may well be, quantitatively and in terms of complex chemistry, the most important of the organic acids capable of binding Ca++ in urine. Since the quantitative determination of citrates in urine became a routine method in many research-orientated urological laboratories thanks to the introduction of standardized enzymatic tests, reports of a reduced excretion of citrates in patients with (recurrent) (oxalate) calculi have become frequent. During our long-term study of patients with recurrent formation of calculi we also observed a clear deficit of citrates in their morning, midday and evening urine. The conspicuous incidence of calculi when there is a concurrence of hypocitraturia and alkaline urine (RTA, in animal experiments: acetazolamide) clearly suggests the lithoprotective significance of citric acid. By quantitatively testing a large number of organic compounds which are interesting both structurally and in terms of complex chemistry, it has been possible to find some substances which restrict crystallization, raise the level of citrates and bind Ca++. A few have also found to restrict the excretion of oxalate in Wistar rats.

[Detection of urinary organic acids by gradual titration of pH 2,0-7,4. Significance for the assessment of the litho-protective characteristic of the examined urine]. / Erfassung der organischen Säuren im Harn durch stufenweise Titrierung von pH 2,0--7,4. Bedeutung für die Abschätzung des lithoprotektiven Charakters des untersuchten Harns.

The role of organic acids in urine is not sufficiently known until today. From our detailed in vitro studies it can be concluded that some of them are highly efficacious in the inhibition of Ca-oxalate and Ca-phosphate crystal growth. Moreover, some of them showed, as acids and as salts, a strong lytic effect on stone-forming crystals and native stone-material. By the oral application to rats, concentrations preventing any precipitation out of meta- and instable Ca-oxalate solutions could be achieved. The renal excretion was controlled by the stepwise titration of preacidified urinary samples from pH 2.0 to 7.4 and the lithoprotective character of urine estimated by the Ca2+-binding capacity.

[In vitro and first in vivo experiments for the dissolution of calcium-containing urinary calculi (author's transl)]. / In-vitro- und erste In-vivo-Versuche zue Lyse calciumhaltiger Harnsteine.

There are numerous reports dealing with the significantly reduced citrate secretion in (recurrent) tone formers. The critical values of the Ca/citrate ratio in the nocturnal urine of (oxalate) stone formers has also been reported, emphasizing the need of medicaments being capable to increase the citrate secretion and to raise the basal citrate level of the nocturnal urine in these patients. In our in vitro experiments, we tested quantitatively the inhibitory activity of some new substances on crystal growth. In Wistar rats we measured the Ca2+-binding capacity as well as the citrate and oxalate excretion before and after oral application of a great number of new compounds. Some of them were highly efficacious in the reduction of the Ca-oxalate activity product, as can be derived from the increased Ca2+-binding capacity and/or the decreased oxalate secretion in urine.

[Calcium concentrations in the urine of recurrent stone-formers and their controls (author's transl)]. / Unkorrigierte sowie osmolarität- und creatininkorrigierte Konzentrationen des ionisierten und des Gesamtcalciums im Harn rezidivierender Steinbildner und gesunder Vergleichspersonen. Ergebnisse einer Langzeitstudie.

Over a period of 4--6 weeks the urinary concentrations of (total calcium, ionized calcium, creatinine and osmolarity in recurrent stone-formers and healthy controls were measured in morning, midday and evening urine samples. The mean urinary concentrations of the (total) calcium were in both groups the same. However, 31% of the stone-formers and only 18% of the controls showed a mean calcium concentration > 5 mmol/l. The ionized calcium, on the contrary, was significantly higher in the stone-formers than in the controls. The lower urinary osmolarity of the recurrent stone-formers led to significantly higher Ca/osmolarity and Ca2+/osmolarity ratios; analogously, the quotient Ca2+/creatinine was also significantly raised in stone-formers.

[Urinary magnesium and its relationship to calcium in recurrent stone-formers and controls (author's transl)]. / Magnesium und seine Relation zum ionisierten und zum Gesamtcalcium im Harn rezidivierender Steinpatienten und gesunder Kontrollpersonen.

Over a period of 4--6 weeks, urine samples were collected three times daily in a group of 16 recurrent stone-formers and in a control group of 11 healthy persons and the urinary concentrations of magnesium, calcium, ionized calcium and creatinine were determined. The Mg-concentrations were distinctly lower in the group of recurrent stone-formers than in the group of healthy controls. The differences were clearly present also in the ratio Ca/Mg, but were diminished in the Mg/creatinine ratio. The Ca2+/Mg-ratio was significantly raised in the group of recurrent stone-formers (p < 0.01) because of the significantly increased Ca2+-concentration and the diminished Mg-concentration in the group of stone-patients. The correlation between the Ca-resp. Ca2+-concentration and the Mg-concentration was in both groups, in the patient and control group, high (r about 0.7).

[Uric acid and oxalate lithiasis. Physico-chemical and crystallo-chemical explanation of the relationship]. / Harnsäure und Oxalatlithiasis. PHysikalisch-chemische und kristallchemische Deutung der Zusammenhänge.

It is tried to explain physico-chemically or crystallo-chemically the so-called "salting out effect", i.e. the influence of the Ca-oxalate precipitation by uric often discussed in urolith research which, indeed, is regarded as real by several researchers and by other investigators refused with emphasis, in order to understand better the connections between hyperuricosuria and oxalate lithiasis which obtrude themselves from the observation material. However, this phenomenon of the facilitated oxalate precipitation at increased uric acid level in the urine further needs directed research.

[Current status of prevention and therapy of urinary calculi and peroral chemo-litholysis with special attention to the relationship of increased excretion of uric acid in oxalate lithiasis]. / Heutiger Stand der Prophylaxe und Therapie des Harnsteinleidens sowie der peroralen Chemolitholyse unter besonderer Berücksichtigung der Zusammenhänge zwischen erhöhter Harnsäureausscheidung und Oxalatlithiasis.

A survey shall be given of the present state of prevention and therapy of urolithiasis as well as of the up to now much restricted possibilities of the chemolitholysis. Particular attention is paid to calcium on account of its participation in the development of oxalate and phosphate calculi which together might be 70--80% of all calculi as well as to the rather limited possibilities of the reduction of the oxalate secretion in the urine. The encouragement of the oxalate lithiasis by increased uric acid in the urine as well as the reduction of the frequency of relapses not only of the concrements of the uric acid but also of the oxalate concrements by the uricostatic Allopurinol (e.g. zyloric) is dealt with.

[Analysis of citric acid and citrates. Citric acid and urolithiasis]. / Analytik der Zitronensäure und Zitrate. Zitronensäure und Urolithiasis.

In the first part the physico-chemical, analytic chemical and physiologic biochemical properties of the citric acid are discussed. In the second part the author enters the role of the citric acid in the formation of uric calculi. In the third part is reported on the individual methods of the determination of citric acid and the method practised in the author's laboratory is described.

[Analysis of oxalic acid and oxalates]. / Analytik der Oxalsäure und Oxalate.

It is reported on individual methods for the estimation of the oxalic acid in body fluids, particularly in the urine. The case in question is a survey of the oxalate estimation methods, which, however, has no pretensions to completeness. The at present most actualestimation methods are brought somewhat more in detail. The data are not sufficient for the laboratorytechnical performance of the individual methods, this would transgress the possibilities of the work. However, the original papers are cited which contain all the necessary details. Some technical difficulties and disturbances in the individual estimation methods are also entered. Despite excellent work of several teams the problems of standardization, of the absolutely reliable reference methoda as well as of an objective consideration of advantages and disadvantages of individual, often subjectively judged methods is not yet solved. Comparing these methods, one gets the impression that several reliable methods of the same value are established. It seems that this estimation method brings the greatest progress which will reliably establish so small quantities of oxalate as they are in the blood or in the liquor. By this also the oxalate clearance and the renal oxalate treatment becomes more exactly establishable than up to now.