Pharmacological evidence for beta3 adrenoceptors in the control of rat gastric acid secretion

The effect of the ₃-adrenoceptor agonist BRL37344 on gastric acid secretion evoked by different secretory stimuli was investigated in anaesthetized rats with lumen-perfused stomachs in comparison with the ₂-adrenoceptor agonist clenbuterol. Intravenous injections of BRL37344 (1–10 mol/kg) and clenbuterol (0.01–1 mol/kg) dose-dependently reduced 2-deoxy-D-glucose-induced acid secretion, with BRL37344 about forty times less potent than clenbuterol. BRL37344 (0.1–3 mol/kg) inhibited pentagastrin-induced acid output, whereas clenbuterol was effective only at high doses (10–100 mol/kg). The inhibitory effect of BRL37344 on pentagastrin-induced acid secretion was not modified by the nonselective –adrenoceptor antagonist propranolol, but it was prevented by bupranolol, a ₃-adrenoceptor antagonist. Furthermore, neither BRL37344 (10 mol/kg) nor clenbuterol (100 mol/kg) modified the acid secretion induced by histamine. These data suggest that ₃ adrenoceptors have an inhibitory role in the control of rat gastric acid secretion induced by indirect stimuli.     

Iron stores in 1359, 30- to 60-year-old Danish women: Evaluation by serum ferritin and hemoglobin

Summary Iron status, including serum (S-)ferritin and hemoglobin (Hb), was assessed in a population survey comprising 1359 nonpregnant Danish women in age cohorts of 30, 40, 50, and 60 years. S-ferritin levels were similar in 30- and 40-year-old women; they displayed a significant increase in 50-year-old women and a further significant increase in 60-year-old women. In the 30- and 40-year-old women, median S-ferritin was 38g/l, 5–95 percentile 6–135g/l; 17.2% had values < 15,g/l (i.e., depleted iron stores), 22.7% values from 15 to 30g/l (i.e., small iron stores), and 60.1% values > 30g/l (i.e., replete iron stores). In the 50-year-old women, median S-ferritin was 54g/l, 5–95 percentile 10–164g/l; 10.3% had values < 15g/l, 16.5% values from 15 to 30g/l, and 73.2% values > 30g/l. For the 60-year-old women, median S-ferritin was 84g/l, 5–95 percentile 25–249g/l; 1.6% had values < 15g/l, 8.6% values from 15 to 30g/l, and 89.8% values > 30g/l. Blood donors (n=180) had lower S-ferritin than nondonors in all age-groups (p<0.001). In the entire series, Hb levels were similar in 30- and 40-year-old women, median 137 g/l (8.5 mmol/l), 5–95 percentile 121–152 g/1 (7.5–9.4 mmol/l), and higher in 50- and 60-year-old women, median 140 g/l (8.7 mmol/l), 5–95 percentile 123-158 g/l (7.6–9.8 mmol/l) (p<0.0001). Hb values < 121 g/l (7.5 mmol/l) were observed in 3.8% of the women. Women with S-ferritin < 15 g/l (n=161) had lower Hb, median 134 g/l (8.3 mmol/l), than those with S-ferritin > 15 g/l, median 139 g/l (8.6 mmol/l) (p<0.001). Iron deficiency anemia (S-ferritin < 15 g/l and Hb < 121 g/l) was seen in 2.3% of 30- and 40-year-old women, and in 1.1% of 50- and 60-year-old women.     

Secretory component and lactoferrin in pure pancreatic juice in chronic pancreatitis

To evaluate pathophysiological roles of proteins in pancreatic secretion, immunoreactive lactoferrin (LF) and secretory component (SC) were measured in the first fraction of the pure pancreatic juice obtained endoscopically from 17 control, 21 suspected (SCP), 14 noncalcified (NCP), and 14 calcified chronic pancreatitis (CCP) subjects. The protein and amylase tended to decrease both in concentration and output from control to CCP. LF concentration was elevated in CCP (18.0±4.9/ml) when compared with controls (2.3±0.2g/ml), and LF output in NCP (12.3±3.8 g/min) was increased from controls (3.8±0.6 g/min). The combination of high LF concentration with low protein output was observed in 10/14 in CCP but 0/14 in NCP and can be a biochemical discriminator of CCP from NCP. SC concentrations were also elevated in NCP (8.5±2.0 g/ml) and CCP (5.6±1.6 g/ml) from controls (1.2±0.2 g/ml). SC outputs in SCP (9.8±3.1 g/min) and NCP (21.1±4.8 g/min) were increased from controls (1.7±0.3 g/min), but there was no further increase in CCP. Hypersecretion of LF and SC in chronic pancreatitis is different, especially in CCP, although the mechanisms for hypersecretion are unknown.This study was supported in part by a research grant for intractable pancreatic disease from the Ministry of Health and Welfare, Japan.     

Comparison of gastric inhibitory polypeptide and intraduodenal or intravenous fat on gastric acid secretion from vagally innervated and denervated canine stomach

Gastric inhibitory polypeptide (GIP), given to dogs in graded doses (range 0.25–2 g/kg/hr) against a constant background stimulation with pentagastrin (4 g/kg/hr), failed to affect the acid secretion at all doses used except the largest one (2 g/kg/hr) which significantly reduced the acid secretion only from the vagally denervated portion of the stomach (Heidenhain pouch, HP) while raising plasma GIP two to three times above the levels reached with duodenal fat. GIP infused in a constant dose (1 g/kg/hr) significantly reduced the HP responses to lower (0.5–2 g/kg/hr) but not to higher (4–16 g/kg/hr) doses of pentagastrin, the kinetics of this inhibition being of competitive type. GIP was ineffective against a constant near maximal stimulation with pentagastrin (4 g/kg/hr), histamine (40 g/kg/hr), or liver extract meal, whereas fat (10 g), given intraduodenally or intravenously, was a powerful inhibitor of acid responses to these stimulants both from the innervated and denervated stomach. Plasma GIP reached similar levels with exogenous GIP and duodenal fat but remained unchanged with intravenous infusion of fat.     

Der Urobilinkörperstoffwechsel des Menschen

Zusammenfassung Es wurde eine Mikromethode zur Bestimmung der Serumurobilinkörper und Harnurobilinkörper mit einem Serumbedarf von 5–10 ml entwickelt. Nach Methanolextraktion und Reduktion wurden die Urobilinkörper in Eisessigäther aufgenommen und nach Ehrlich-Reaktion in wäßriger Lösung spektralphotometrische Konzentrationsbestimmungen durchgeführt. Die Serumurobilinkörperkonzentration bei 17 Normalpersonen betrug 2.3±1.7 g%, die methodische Streubreite (2 )±18%, 7 Patienten mit Virushepatitis hatten eine erhöhte Serumkonzentration von 10.6±6.9 g%.Die tageszeitliche Schwankung der Serumurobilinkörperkonzentration (9–19 Uhr) betrug±73% (2 ) des Mittelwertes.

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Summary A micromethod has been developed for the determination of serum and urine urobilinoids, demanding 5–10 ml serum.After methanol-extraction and reduction, the urobilinoids were transferred to aceticacid-ether. After Ehrlich-reaction, concentration was determined in aqueous solution by spectrophotometric measurement.The concentration of serum urobilinoids at 17 normal adults was 2.3±1.7 g%, the methodical 2 -deviation ±18%. At seven patients with virus hepatitis serum concentration was elevated to 10.6±6.9 g%.Changes of concentration of serum urobilinoids at 5 persons during a day (9 a. m. – 19. p. m.) were ±73% (2 ) of average concentration.

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Studie im Rahmen des Assoziationsvertrages Strahlenhämatologie GSF-EURATOM Nr. 031-64-I BIAD.     

Inhibition of basal and stimulated gastric H+ and pepsin secretion in duodenal ulcer patients by metiamide,an H-2 histamine antagonist

Metiamide was given orally in one dose of 200 mg in 23 studies in patients with duodenal ulcer, 4 in the basal state, 11 during histamine infusion, and 8 before insulin hypoglycemia stimulation. In the latter 8 patients insulin was given at another time without metiamide. In 17 studies acid secretion was suppressed by metiamide—up to 75% in the basal state, 53% after histamine, and 80% after insulin. Pepsin secretion was reduced to the same extent as H⁺ in the histamine studies but not in the basal (57%) or insulin (44%) studies, so that in the latter pepsin/acid ratios were 3-fold greater than in controls. Blood levels of metiamide were measured in 17 studies. In 10 out of 11 who showed inhibition of 40% or more, peak blood levels of metiamide were 0.45 g/ml to 1.25 g/ml. In 5 of 6 who did not show inhibition, blood levels were 0.05–0.4 g/ml; in the sixth it was 0.8 g/ml. Therefore a critical blood level for suppression of basal or stimulated secretion appears to be 0.45 g/ml.Supported by Public Health Service Grants AM09260 and AM05286; and by a Grant-in-Aid from Smith Kline & French Laboratories; Veterans Administration Hospital, Birmingham, Alabama, Research Project 3649-01.     

Esophageal carcinoma in house musk shrews,Suncus murinus (insectivora), induced by N-methyl-N′-nitro-N-nitrosoguanidine

Female 6-week-old shrews were given a solution ofN-methyl-N-nitroN-nitrosoguanidine (MNNG) at a concentration of 50 g/ml or 100 g/ml in the drinking water. All 11 shrews receiving 100 g/ml MNNG died 8–13 days after the beginning of carcinogen administration and 6 of the 20 shrews receiving 50 g/ml MNNG died after 10–54 days. When animals were between 43 and 54 weeks of age, multiple esophageal lesions were evoked in all 14 that had received 50 g/ml MNNG for 30 weeks. All shrews developed a protruding, ulcerative, or superficial type of squamous-cell carcinoma of the esophagus, accompanied by papillomas. Local invasion was seen in squamous-cell carcinoma but no distant metastasis was noted. None of the 5 control shrews developed any esophageal abnormality. No gastric adenocarcinoma, intestinal sarcoma, or other tumors were induced with MNNG. It can be concluded that MNNG has a carcinogenic effect on shrew esophageal epithelium.Abbreviations MNNG N-methyl-N-nitro-N-nitrosoguanidine - ENNG N-ethyl-N-nitro-N-nitrosoguanidine - BrdU 5-bromo-2-deoxyuridine     

B cell adrenoceptors and sulphonylurea-induced insulin release in mouse islets

Summary Interactions of tolbutamide and glibenclamide with B cell adrenoceptors have been reported. This study evaluated the possible role of such interactions in the stimulation of insulin release. Mouse islets were incubated in the presence of 10 mmol/l glucose alone or with tolbutamide (10 mol/l) or glibenclamide (0.02 mol/l). At 0.01–10 mol/l, blockers of ₂-adrenoceptors (yohimbine, idazoxan) or ₁-adrenoceptors (prazosin) had practically no effect on glucose-induced insulin release and did not affect its potentiation by sulphonylureas, except for a slight increase by 10 mol/l prazosin and idazoxan. Nonspecific -blockers (phentolamine, dihydroergotamine) increased control release at 10 mol/l, but only the latter amplified the response to tolbutamide. Blockers of -adrenoceptors were tested at 0.1–100 mol/l: propranolol (₁, ₂), metoprolol (₁) and compound ICI 118-551 (₂). They increased glucose-induced insulin release at 100 mol/l but variably altered the effect of sulphonylureas. Blockers of adrenoceptors have, thus, no effect on insulin release in vitro at therapeutic concentrations. At high concentrations, they non-specifically affect the action of sulphonylureas. We conclude that an interaction with B cell adrenoceptors is not involved in the insulinotropic action of sulphonylureas.     

Insulin levels in the umbilical vein and in the umbilical artery of newborns of normal and gestational diabetic mothers

Summary Insulin levels (by double antibody radioimmunological assay) were studied in the venous blood of mothers at vaginal delivery and in the umbilical vein and artery of their newborns. — In 14 normal mothers the insulin levels after 10 hours fasting were 18.5±3.6 U/ml (mean±S.E.M.). In their newborns (mean: 3.420 kg, all < 4.000 kg, 38–41 weeks gestation) the insulin levels were low and similar in the umbilical vein (5.6±0.7 U/ml) and in the umbilical artery (6.6±0.7 U/ml). The plasma glucose levels in the mothers were 99.7±3.9 mg/100 ml and in the umbilical vein 77.3±3.7 mg/100 ml and the umbilical artery 65.5±3.2 mg/100 ml. They were significantly different from each other. — Eleven normal mothers receiving a glucose infusion (ca. 15 g/3 hours) during delivery had 42.0±9.9 U/ml insulin in their venous blood. In their newborns with a normal birth-weight (mean: 3.585 kg, all < 4.000 kg) the insulin levels were not increased either in the umbilical vein (7.0±1.0 U/ml) or in the artery (7.9±1.0 U/ml). The plasma glucose levels in the mothers were 128.0±7.7 mg/100 ml, and in the umbilical vein 105.0±7.5 mg/ 100 ml and in the umbilical artery 88.8±8.6 mg/100 ml. The plasma glucose levels were significantly different from each other. — In six infants with large birthweight (> 4.100 kg) born to untreated mothers with gestational diabetes the insulin levels were superior to the values found in normal newborns. In three of these infants, born to mothers who did not receive a glucose infusion, the insulin levels in the umbilical vein were 38, 42 and 13 U/ml, and in the artery they were 17, 34.5 and 18.5 U/ml. The other three mothers received a glucose infusion, their newborns had in the umbilical vein an insulin level of 15.5, 65 and 19 U/ml and in the artery 20, 72.5 and 14 U/ml. — In conclusion, the normal infant at birth has a low insulin level, which is equal in the umbilical vein and artery. In 6 heavy infants born to untreated latent diabetic mothers, the insulin levels were significantly higher than in normals, and the levels in the umbilical vein and the artery were different from one another. This latter data on hyperinsulinism is discussed in relation with hyperplasia of the islets of Langerhans observed in stillborn infants of mothers with insulin-dependant diabetes or gestational diabetes.Aspirant du Fonds National de la Recherche Scientifique     

Untersuchungen zum antilipolytischen Effekt des Insulins am menschlichen Fettgewebe in vitro

Zusammenfassung Am menschlichen Fettgewebein vitro wurde die Hemmung der Lipolyse durch Insulin in glucosefreiem Medium untersucht. Als Parameter der lipolytischen Aktivität wurde die Produktion von Glycerin und freien Fettsäuren bezogen auf Gewebe-Feuchtgewicht gemessen. Die Metabolitfreisetzung durch Fettgewebsschnitte von 25 Normalpersonen betrug in glucosefreiem Medium unter basalen Bedingungen 0.57 ± 0.20 Mol Glycerin/g Gewebe-Feuchtgewicht/2 Std und 2.6 ± 0.8 Eq freie Fettsäuren/g Gewebe-Feuchtgewicht/2 Std — Die Lipolyse wurde durch Zusatz von Noradrenalin oder Adrenalin in Konzentrationen von 0.01 g/ml oder mehr stimuliert. Bei Konzentrationen von 0.1 und 1.0 g Katecholamin/ml ergaben sich submaximale Steigerungen der Metabolitfreisetzung auf rund das Doppelte des Basalwertes. Die mit beiden Hormonkonzentrationen erzielten Effekte waren nicht signifikant unterschiedlich, jedoch bei Noradrenalin signifikant größer als bei Adrenalin. — Zusatz von Insulin zum Inkubationsmedium hemmte die Lipolyse. Durch 33 E Insulin/ml wurde bei Fettgewebsschnitten von 18 Normalpersonen die basale Produktion von Glycerin auf 66 ± 21% und von freien Fettsäuren auf 67 ± 24% reduziert. Auch bei gleichzeitiger submaximaler Stimulation durch Katecholamine betrug die Hemmung der Lipolyse rund 1/3. — Die Konzentration-sabhängigkeit des Insulineffekts auf die Katecholamin-stimulierte Lipolyse wurde an Fettgewebsschnitten von 14 Normalpersonen geprüft. Eine signifikante Lipolyse-hemmung wurde mit einer Konzentration von 1.0 E Insulin/ml im Inkubationsmedium erzielt. Durch 100 E/ml wurde die durch Katecholaminzusatz bedingte Stimulation der Lipolyse aufgehoben. — Diein vitro nachweisbare hohe Insulinempfindlichkeit der Lipolyse des menschlichen Fettgewebes läßt darauf schließen, daß die Fettmobilisation auch unter physiologischen Bedingungenin vivo unabhängig vom Glucosestoffwechsel durch Insulin reguliert wird.

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Investigations of the antilipolytic effect of insulin on human adipose tissue in vitro

Summary The antilipolytic effect of insulin on human adipose tissue was studied employing glucose-free incubation medium. The lipolytic activity was measured by the production of glycerol and free fatty acids, and calculated per g wet weight of tissue. Slices of adipose tissue, which was obtained after an overnight fast from 25 subjects selected for lack of metabolic or endocrine diseases, released 0.57 ± 0.20 moles glycerol/g tissue/2 h, and 2.6 ± 0.8 eq. free fatty acids/g tissue/2 h. — Lipolysis was increased by addition of 0.01 or more g epinephrine or norepinephrine per ml of medium, the increment produced by 0.1 or 1.0 g catecholamine/ml being about 100% of the basal rate. However, the effect of norepinephrine was significantly greater than the effect of epinephrine. — Addition of insulin to the medium inhibited lipolysis. 33 U of insulin per ml decreased the release of glycerol to 66 ± 21 % and the release of free fatty acids to 67 ± 24% of the basal rate. A reduction of lipolysis by about 1/3 was also seen when lipolysis was stimulated by 0.1 or 1.0 g catecholamine per ml. — The dose response of the insulin effect on stimulated lipolysis was studied in slices of adipose tissue from 14 normal subjects. A significant inhibition of lipolysis was demonstrated with 1.0 U of insulin per ml. The lipolytic effect of 0.1 or 1.0 g catecholamine per ml was completely inhibited by 100 U insulin per ml. — The marked insulin sensitivity of lipolysis in human adipose tissuein vitro would be in agreement with the concept, that mobilization of depot fat under physiological conditionsin vivo is regulated by insulin, independent of glucose metabolism.

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Etude de l'effet antilipolytique de l'insuline sur le tissu adipeux humain in vitro

Résumé Les auteurs ont étudié l'effet antilipolytique de l'insuline sur le tissu adipeux humain en utilisant un milieu d'incubation ne contenant pas de glucose. L'activité lipolytique a été mesurée d'après la production de glycérol et d'acides gras libres, et calculée par g de poids humide de tissu. Des coupes de tissu adipeux obtenu à partir de 25 sujets à jeun depuis la veille au soir et n'ayant pas de maladies métaboliques ou endocriniennes, libéraient 0.57 ± 0.20 mol de glycérol/g de tissu en 2 h, et 2.6 ±0.8 Eq d'acides gras libres/g de tissu en 2 h. La lipolyse était augmentée par addition de 0.01 g ou plus d'adrénaline ou de noradrénaline par ml, l'augmentation produite par 0.1 ou 1.0 g de catécholamine/ml étant environ de 100% par rapport au taux de base. Cependant, l'effet de la noradrénaline était significativement plus grand que celui de l'adrénaline. L'addition d'insuline au milieu inhibait la lipolyse. 33 U d'insuline par ml réduisaient la libération de glycérol à 66± 21 % et la libération d'acides gras libres à 67 ± 24% du taux de base. Une réduction de la lipolyse d'environ 1/3 a été également observée quand la lipolyse était stimulée par 0.1 ou 1.0 g de catécholamine par ml. La relation effet-dose de l'insuline sur la lipolyse stimulée a été étudiée sur des coupes de tissu adipeux de 14 sujets normaux. Une inhibition significative de la lipolyse a été constatée avec 1.0 U d'insuline par ml. L'effet lipolytique de 0.1 ou 1.0 g de catécholamine par ml était complètement inhibé par 100 U d'insuline par ml. La sensibilité marquée de la lipolyse à l'insuline dans le tissu adipeux humain in vitro serait en accord avec l'idée que la mobilisation des graisses en dépôt dans les conditions physiologiques in vivo est régulée par l'insuline indépendamment du métabolisme du glucose.

     

Serum sialic acid in malignant tumors,bacterial infections,and chronic liver diseases

Summary The total serum sialic acid concentration was determined in 2,264 persons with various malignant tumors, bacterial infections, rheumatic diseases, and chronic liver diseases, and in a control group. The thiobarbiturate method according to Warren was used [34].The upper limit (95% percentile) in the control group was 2.23 mol/ml. Higher values were found in the groups with neoplasms (mean: 3.04 mol/ml), inflammatory diseases (e.g., pneumonia: 3.02 mol/ml), and active rheumatoid arthritis (3.05 mol/ml). In the group with malignant diseases, the sialic acid concentration at the time of diagnosis was highest for bronchial carcinoma (3.29 mol/ml) and lowest for breast cancer (2.58 mol/ml). In chronic liver diseases the mean sialic acid level was lower than in a heterogeneous group of noninflammatory and nonneoplastic diseases.The estimation of the serum sialic acid concentration could be useful in the detection of tumor burden and metastases, and in the evaluation of the later course and prognosis of malignant neoplasms if bacterial/inflammatory and active rheumatoid processes can be excluded.     

Induction and activation of procollagenase in rabbit synovial fibroblasts after treatment with active oxygen released by xanthine/xanthine oxidase

Treatment of rabbit synovial fibroblasts with active oxygen (AO) released by xanthine/xanthine oxidase resulted in an induction of procollagenase in these cells in concentrations ranging from 12.5 g/ml xanthine plus 0.0025 U/ml xanthine oxidase to 50 g/ml xanthine plus 0.01 U/ml xanthine oxidase. Preceding this there was an accumulation of poly(ADP-ribose) for the same concentration range of xanthine/xanthine oxidase. Furthermore, it was found that AO caused activation of the latent procollagenase to the active enzyme in concentrations ranging from 0.1 g/ml xanthine plus 0.00002 U/ml xanthine oxidase to 1 g/ml xanthine plus 0.0002 U/ml xanthine oxidase. It is suggested that poly(ADP-ribosyl)ation participates in the induction of procollagenase by relaxing chromatin. Furthermore, it is proposed that AO activates latent procollagenase under physiological conditions.     

C-reactive protein (CRP) levels in systemic lupus erythematosus (SLE)

Summary CRP levels in 194 serum samples from 43 SLE patients were measured. Patients with inactive disease have levels below 10 g/ml; patients with active SLE have higher levels, but never over 50 g/ml. In the presence of infection or inflammatory processes, regardless of the activity of SLE, the levels are significantly higher (p<0.05), and well over 50 g/ml. Both active SLE patients and inactive SLE patients with local infections have levels between 10 g/ml and 50 g/ml. In this situation, the presence of anti-DNA antibodies strongly suggests disease activity (82% versus 9%, p<0.05). The clinical and physiopathological meaning of these findings is discussed.     

Dose/response study of the effects of oestrogens on tumour growth and morphology in the Dunning R3327 prostatic adenocarcinoma

Summary The present study was undertaken to investigate to what extent the oestrogen-induced effects on growth and morphology of the Dunning R3327 rat prostatic adenocarcinoma are dose-dependent. Castrated and testosterone-supplemented rats were used in order to study effects of increasing doses of oestrogens on the tumour. It was found that the lowest dose of oestradiol-17 that reduced the overall growth, the volume density of the epithelium and epithelial cell area in Dunning R3327 prostatic tumours is 10 g given as daily injections. Higher oestrogen doses (50 g, 200 g, and 500 g), in addition to reducing the volume of tumour epithelium, also induced an increase of the volume density of tumour stroma. The area of stroma cell nuclei was increased by 50 g and 200 g oestradiol-17. These observation, may indicate that the lowest effective oestrogen dose is different in the epithelium and stroma of Dunning tumours and that large doses of oestrogen stimulate the stromal compartment. This stimulatory effect did not influence the inhibitory effects seen on the overall growth of the tumour and on the tumor epithelium.     

The role of myocardial edema in the left ventricular diastolic stiffness

Summary It has been shown that simultaneous administration of norepinephrine (10 g/kg/min) and drotaverine (200 g/kg/min) does induce interstitial myocardial edema which tends to increase left ventricular diastolic stiffness. These results suggest that in myocardial ischaemia temporary increase of left ventricular diastolic stiffness may be caused by interstitial edema.

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Die Bedeutung des Myokardödems für die diastolische Steifheit des linken Ventrikels

Zusammenfassung Es wurde bewiesen, daß die gleichzeitige, intravenöse Verabreichung von Noradrenalin (10 g/kg/min) und Drotaverin (200 g/kg/min) ein vorübergehendes interstitielles Myokardödem hervorruft, das zur diastolischen Erhöhung der linken Herzkammerwandsteifheit führt. Die Beobachtung läßt vermuten, daß die bei Myokardischämie zeitweilig in Erscheinung tretende, diastolische Erhöhung der linken Kammerwandsteifheit durch ein vorübergehendes, interstitiales Gewebsödem verursacht werden kann.

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With 3 figures and 1 table     

Plasma levels of secretory IgA in patients with gastric cancer

Summary The levels of plasma secretory IgA were measured in patients with gastric cancer and found to be slightly higher (9.6±6.2 g/ml) than those in healthy controls (7.0±2.6 g/ml, 0.05<P<0.1). Secretory IgA levels in those with hepatic metastases (19.7±12.2 g/ml) were significantly higher than those in patients without hepatic metastases (P<0.001). In the latter, there was no significant relationship between plasma secretory IgA levels and the deepest layer of cancerous invasion or lymph node metastases. The secretory IgA levels in cases of well differentiated tubular adenocarcinoma were significantly higher than those with poorly differentiated adenocarcinoma (P<0.05). Although there is small diagnostic value in the detection of gastric cancer by measuring the levels of secretory IgA, high levels of secretory IgA in gastric cancer patients may be indicative of the presence of hepatic metastases.     

Effect of small doses of somatostatin analog,octreotide, on gallbladder contractility in normal Chinese adults

The acute effects of single different doses of the somatostatin analog octreotide on the contractility of the gallbladder stimulated by fatty meal were studied in six healthy Chinese volunteers. Gallbladder contraction after a fatty meal was significantly suppressed by octreotide at doses of 50, 25, 12.5, and 5 g. Mean duration of suppression lasted for more than 10 hr at doses of 25 and 50 g, after which the gallbladder contractility was restored at 24 hr in three and four, respectively, of the six subjects. The percentage of relative gallbladder contraction (PRGC) in all subjects receiving 12.5 and 5 g octreotide returned to pretreatment values at 10 hr but had not returned to normal 6 hr after the injection of 5 g octreotide. In summary, octreotide inhibits the contraction of the gallbladder even with a dose as low as 5 g. It appears that it may not be possible to avoid gallbladder dysfunction during long-term octreotide therapy by decreasing the dose. Further studies including modalities to increase the contractility of the gallbladder are recommended.     

Assessment of nucleolar organizer regions by automatic image analysis in breast cancer: correlation with DNA content,proliferation rate,receptor status and histopathological grading

Summary The value of automatic image analysis in the investigation of nucleolus regions (AgNOR) has been examined in tissue sections of 52 malignant and 30 benign breast lesions. Determination of the AgNOR number per cell alone revealed a considerable overlap between benign (range 1.2–3.8) and malignant specimens (range 1.5–16.2). They differed however, highly significantly (P<0.001) in their AgNOR sizes. In benign breast disorders the mean AgNOR area per tumour ranged from 0.22 m² to 1.07 m² (mean 0.39 m²), whereas in carcinomas AgNOR sites ranged from 0.05 m² to 0.22 m² (mean 0.09 m²). AgNOR counts showed a good correlation with histopathological grade (P<0.05), aneuploidy (P<0.01), proliferation rate as determined by Ki67 immunostaining (P<0.01), as well as oestrogen and progesterone receptor content (P<0.01). Image analysis proved to be advantageous over AgNOR counting alone as it facilitated the standardization of the AgNOR technique itself and thus, significantly improved its diagnostic specifity.Abbreviations AgNOR nucleolar organizer regions demonstrated by silver staining - Ki67 proliferation marker Dedicated to Professor Dr. D. Schmähl on the occasion of his 65th birthdaySupported in part by a grant from the Bundesminister für Forschung und Technologie and by the P. E. Kempes Foundation     

Granulocyte Elastase in Cirrhotic Patients with Spontaneous Bacterial Peritonitis

Granulocyte elastase (GE) is a powerfulproteolytic enzyme that is released by PMNs whendegranulated in infectious processes. The aim of thisstudy was to measure GE in ascites and plasma ofcirrhotic patients with spontaneous bacterial peritonitis(SBP). We studied 29 cirrhotic patients, 17 of themhaving SBP (group A). Twelve patients with noninfectedascites formed the control group (group B). At the time of diagnosis of SBP, GE levels inascites (183.17 ± 86.11 g/liter) and plasma(114.6 ± 35.99 g/liter) were higher in groupA than in group B (27.41 ± 11.54 g/liter, P< 0.00001 and 82.54 ± 20.52 g/liter, P = 0.01,respectively). Levels of GE in ascites had a high valuefor discriminating between patients with and withoutSBP. In the patients who responded to the initialantibiotic treatment, these values significantly decreasedin ascites (67.69 ± 54.22 g/liter, P = 0.003)and plasma (67 ± 22.39 g/liter, P = 0.01) 48hr after therapy was started, in parallel with thedecrease of PMN in ascites. In patients who did notrespond, the production of GE remained elevated.Patients who developed renal insufficiency following SBPhad more marked elevation of GE in plasma (144.8± 33.43 g/liter) than those with normal renalfunction (99.5 ± 27.53 g/liter, P = 0.02).These results suggest that the measurement of GE may behelpful for the diagnosis of SBP in patients withcirrhosis and for assessing the efficacy of therapy. Inaddition, the release of GE into plasma may contributeto the impairment of renal function that follows SBP insome patients.     

Catecholamines and tumour promoting phorbolesters inhibit insulin receptor kinase and induce insulin resistance in isolated human adipocytes

Summary The effect of the catecholamine isoprenaline (10^–5mol/l) and of the tumour promoting phorbolester tetradecanoyl--phorbol acetate (10^–9mol/l) on insulin stimulated 3-O-methyl-glucose transport was studied in freshly isolated human adipocytes. Both substances reduced the maximal responsiveness of the glucose transport system to insulin by approximately 50%. To test if this is caused by inhibition of the insulin receptor kinase the receptor from phorbolester and isoprenaline treated cells was solubilized, partially purified and its kinase activity studied in vitro. Insulin stimulated ³²P-incorporation into the -subunit of the insulin receptor of phorbolester or isoprenaline treated cells was reduced to 20–60% of the values found with receptor from control cells at insulin concentrations between 10^–10mol/l and 10^–7mol/l. This inhibition of kinase activity of receptor from phorbolester and isoprenaline treated cells was observed at nonsaturating adenosine triphosphate levels (5 mol/l), and it could be overcome with higher concentrations of -³²P-adenosine triphosphate in the phosphorylation assay. A Lineweaver Burk analysis of the insulin stimulated receptor phosphorylation revealed that the Michaelis constant for adenosine triphosphate of the receptor kinase from phorbolester and isoprenaline treated cells was increased to >100 mol/l compared with <50 mol/l for receptor from control cells. We conclude from the data that catecholamine and phorbolester treatment of human adipocytes modulates the kinase activity of the insulin receptor by increasing its Michaelis constant for adenosine-triphosphate, and propose that this modulation of receptor kinase is a mechanism that can contribute to the pathogenesis of insulin resistance in human fat cells.