Testicular cancer: prognostic implications of vascular invasion.

In a retrospective study the primary tumors of 33 patients with seminomas and 53 with nonseminomatous germ cell tumors were re-evaluated for vascular invasion. The significance of vascular invasion was analyzed in respect to the appearance of visceral metastases and the effect of adjuvant chemotherapy. Vascular invasion was demonstrated in 27 per cent of the patients with seminomas and 53 per cent with nonseminomatous germ cell testis tumors, while visceral metastases appeared in 9 and 32 per cent, respectively.

[Is lymphadenectomy in stage I of non-seminomatous testicular cancer still justified?].

Testicular cancer is the tumour of the male genital tract which is most easily and successfully treated today. This very circumstance dictates that for ethical reasons we are more bound than ever to prevent unnecessary diagnostic and therapeutic procedures in these young patients. They should receive only the maximum necessary and not the maximum possible therapy.

Degradation of cholecystokinin octapeptide by the neutral endopeptidase EC 3.4.24.11 and design of proteolysis-resistant analogues of the peptide.

Inactivation of cholecystokinin octapeptide in vitro involves a metalloendopeptidase (EC 3.4.24.

Stimulatory and inhibitory effects of TMB-8 on pancreatic enzyme secretion.

The putative intracellular calcium antagonist 3,4,5-trimethoxybenzoate 8-(diethylamino)-octyl ester (TMB-8) affects carbachol-induced enzyme secretion from rabbit pancreatic acini in a different way than it does that induced by either the C-terminal octapeptide of cholecystokinin (CCK-8), the phorbol ester, 12-O-tetradecanoylphorbol 13-acetate (TPA) or the calcium ionophore, A23187. In the presence of TMB-8 the dose-response curve for carbachol-induced amylase release shifts to the right, suggesting competitive antagonism at the muscarinic receptor. The hypothesis that TMB-8 acts as a muscarinic receptor antagonist is supported by the observation that TMB-8 dose-dependently inhibits the carbachol-, but not CCK-8-induced increases in cytosolic free calcium, measured in acinar cells by means of the fluorescent calcium indicator quin2.

Nucleotide specificity of the E2K----E1K transition in (Na+ + K+)-ATPase as probed with tryptic inactivation and fragmentation.

The nucleotide specificity for the E2K----E1K conformational transition in (Na+ + K+)-ATPase as the key step for overall hydrolytic activity and coupled cation transport has been investigated. Use has been made of tryptic inactivation, which is biexponential in time for the enzyme in the presence of Na+ with or without nucleotides (E1 conformation) and monoexponential in the presence of K+ (E2 conformation). ATP, AdoPP[NH]P and CTP in order of decreasing effectivity induce the biphasic tryptic inactivation pattern in the presence of K+.

Presence of a low-affinity nucleotide binding site on the (K+ + H+)-ATPase phosphoenzyme.

The effects of Mg2+ and nucleotides on the dephosphorylation process of the (K+ + H+)-ATPase phosphoenzyme have been studied. Phosphorylation with [gamma-32P]ATP is stopped either by addition of non-radioactive ATP or by complexing of Mg2+ with EDTA. The dephosphorylation process is slow and monoexponential when dephosphorylation is initiated with ATP.

[HTLV-III serology, epidemiology and clinical aspects of imprisoned i.v. drug-dependent males in Austria].

Sera of 71 intravenous drug abusers imprisoned in Austria were tested for HTLV-III antibodies and the results correlated with the case histories and available clinical data. 12 sera, i.e.

Buffering capacity of human semen.

The buffering capacity of 270 semen samples derived from 196 men of infertile couples was determined from titration curves. The average buffering capacity in the physiologic range (pH 7.0 to 6.

Eosin, a fluorescent marker for the high-affinity ATP site of (K+ + H+)-ATPase.

Eosin has been used as a fluorescent probe for studying conformational states in (K+ + H+)-ATPase. The eosin fluorescence level is increased by Mg2+ (K0.5 = 0.

Sodium and buffer cations inhibit dephosphorylation of (Na+ + K+)-ATPase.

Effects of various cations on the dephosphorylation of (Na+ + K+)-ATPase, phosphorylated by ATP in 50 mM imidazole buffer (pH 7.0) at 22 degrees C without added Na+, have been studied. The dephosphorylation in imidazole buffer without added K+ is extremely sensitive to K+-activation (Km K+ = 1 microM), less sensitive to Mg2+-activation (Km Mg2+ = 0.

Free protons do not substitute for sodium ions in buffer-mediated phosphorylation of (Na+ + K+)-ATPase.

In view of our recent finding of imidazole-activation of the phosphorylation of (Na+ + K+)-ATPase and the suggestion by others of an activating role of protons, in lieu of sodium ions, in the overall hydrolytic and phosphorylation processes of the enzyme, we have investigated the effect of pH on the phosphorylation process. No indication of proton activation is found. Rather, phosphorylation at low pH in the absence of Na+ is dependent on the buffer concentration.

Direct evidence for an ADP-sensitive phosphointermediate of (K+ + H+)-ATPase.

Direct evidence for the occurrence of an ADP-sensitive phosphoenzyme of (K+ + H+)-ATPase, the proton-pumping system of the gastric parietal cell is presented. The enzyme is phosphorylated with 5 microM [gamma-32P]ATP in 50 mM imidazole-HCl (pH 7.0) and in the presence of 7-15 microM Mg2+.

The locus of nucleotide specificity in the reaction mechanism of (Na+ + K+)-ATPase determined with ATP and GTP as substrates.

ATP and GTP have been compared as substrates for (Na+ + K+)-ATPase in Na+-activated hydrolysis, Na+-activated phosphorylation, and the E2K----E1K transition. Without added K+ the optimal Na+-activated hydrolysis rates in imidazole-HCl (pH 7.2) are equal, but are reached at different Na+ concentrations: 80 mM Na+ for GTP, 300 mM Na+ for ATP.

Ouabain- and potassium-induced stimulation of amylase release in fragments and acini of rabbit pancreas.

Ouabain increases the enzyme secretion from the isolated rabbit pancreas and pancreatic fragments, but not from isolated pancreatic acini. The increase occurs after a delay of 45-60 min and is not accompanied by an increase in lactate dehydrogenase release. The stimulatory effect of ouabain (10(-5) M) is dependent on the presence of extracellular calcium, and is not antagonized by 10(-4) M atropin, 10(-4) M propranolol, 10(-5) M phentolamine, 10(-3) M dibutyryl-cyclic GMP, 10(-6) M tetrodotoxin, 10(-4) M verapamil or 10(-4) M D-600.

CHOP-firstline treatment in NHL with unfavorable prognosis--evaluation of therapeutic response and factors influencing prognosis.

58 NHL-patients (9 large cell centrocytic, 18 centroblastic, 16 immunoblastic, 15 lymphoblastic lymphomas) were treated immediately after diagnosis with CHOP-chemotherapy regardless of the extent of disease. Because of the advanced age of the majority of patients (median age 61 years, range 22-85 years) a reduced dose in the first two cycles was administered. Statistically significant prognostic variables influencing survival were the following: histologic subtypes according to the Kiel-classification (p less than 0,05), B-symptoms (p less than 0,001), blood sedimentation rate (p less than 0,02) and LDH (p less than 0,0005).

Na+-like effect of imidazole on the phosphorylation of (Na+ + K+)-ATPase.

A high basal level of phosphorylation (approx. 70% of the optimal Na+-dependent phosphorylation level) is observed in 50 mM imidazole-HCl (pH 7.0), in the absence of added Na+ and K+ and the presence of 10-100 microM Mg2+.

Tight junctional permeability of the resting and carbachol stimulated exocrine rabbit pancreas.

The permeability of the pancreatic epithelium to horseradish peroxidase is investigated in the resting and carbachol stimulated rabbit pancreas. Horse radish peroxidase administered to the bathing medium of the isolated rabbit pancreas appears in the secreted fluid of the pancreas in a relatively low concentration. Carbachol stimulates both protein secretion and the passage of horse radish peroxidase into the secretory fluid.

The mechanism of fluid secretion in the rabbit pancreas studied by means of various inhibitors.

In order to increase our understanding of the mechanism of pancreatic fluid secretion we have studied the effects of various transport inhibitors on this process in the isolated rabbit pancreas. In this preparation, a high rate of unstimulated fluid secretion occurs, which probably originates from the ductular cells. Inhibitory are ouabain, furosemide, bumetanide, piretanide, 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS) and acetazolamide, with their half-inhibitory concentrations: 2 X 10(-6) M (ouabain), 1.

Potentiating role of cyclic AMP in pancreatic enzyme secretion, demonstrated by means of forskolin.

The role of cyclic AMP in the regulation of enzyme secretion by the rabbit pancreas has been investigated by means of forskolin, an activator of the catalytic subunit of adenylate cyclase. Forskolin increases the cyclic AMP level in isolated pancreatic acini in a dose-dependent way. Basal amylase release, however, remains unchanged.

Amino group modification of (Na+ + K+)-ATPase.

The effects of three amino group reagents on the activity of (Na+ + K+)-ATPase and its component K+-stimulated p-nitrophenylphosphatase activity from rabbit kidney outer medulla have been studied. All three reagents cause inactivation of the enzyme. Modification of amino groups with trinitrobenzene sulfonic acid yields kinetics of inactivation of both activities, which depend on the type and concentration of the ligands present.

Anion secretion by the isolated rabbit pancreas.

The isolated rabbit pancreas secretes a fluid containing chloride and bicarbonate in about equal concentrations. Replacement of bicarbonate by acetate, phosphate or isethionate, replacement of Na+ by Li+ and addition of ouabain to the bathing medium of the pancreas inhibit the secretion of fluid, chloride and bicarbonate in a similar fashion and by maximally 100%. Replacement of chloride by isethionate inhibits fluid secretion by maximally 50%, chloride secretion by 90% and bicarbonate secretion by 20%.

Thiophosphorylation of (Na + K+)-ATPase yields an ADP-sensitive phosphointermediate.

1) Treatment of (Na+ + K+)-ATPase from rabbit kidney outer medulla with the gamma-35S labeled thio-analogue of ATP in the presence of Na+ + Mg2+ and the absence of K+ leads to thiophosphorylation of the enzyme. The Km value for [gamma-S]ATP is 2.2 microM and for Na+ 4.

The H+/ATP transport ratio of the (K+ + H+)-ATPase of pig gastric membrane vesicles.

Various values have been reported for the H+/ATP transport ratio of the (K+ + H+)-ATPase of the gastric parietal cell: 4, 2 and 1. We have, therefore, reinvestigated this matter with a vesicle preparation isolated from pig gastric mucosa. The vesicles are suspended in glycylglycine buffer (pH 6.

Amiloride is a cholinergic antagonist in the rabbit pancreas.

The effect of amiloride on fluid and protein secretion in the isolated rabbit pancreas and on amylase secretion in rabbit pancreatic acini has been studied. Amiloride (1 mM) has no effect on the pancreatic fluid secretion either in a normal incubation medium (143 mM Na+), or in a medium containing only 25 mM Na+. The carbachol-induced enzyme secretion is inhibited by amiloride in both systems, whereas the enzyme secretion induced by the C-terminal octapeptide of cholecystokinin ( PzO ) is not affected.