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M von der Ohe

Publications and source records attributed to M von der Ohe.

At least 19 recordsLinked to original sources
PubMed2001

Human neutrophils produce macrophage inhibitory protein-1beta but not type i interferons in response to viral stimulation.

Several cell types have been shown to produce type I interferons (IFN). Of human leukocytes, monocytes and especially type 2 dendritic cell precursors (pDC2) seem to be the main producers and also have a wide spectrum of cytokine production. However, neutrophils seem to have a limited capacity for cytokine production but possess efficient defense mechanisms vs. bacterial infection by phagocytosis and degranulation. To determine whether they also have antiviral functions, IFN-alpha and IFN-beta were measured in preparations of pure neutrophils. The capacity of neutrophils to produce type I IFN is controversial. Additionally, macrophage inflammatory protein-1alpha (MIP-1alpha) and MIP-1beta were measured, as they are described to have indirect or direct antiviral activity. As stimulants, active and inactivated Newcastle disease virus (NDV), Sendai virus, and granulocyte colony-stimulating factor (G-CSF) were used. Peripheral blood mononuclear cells (PBMC) from the same donors were highly reactive to viral stimulation, whereas neutrophils failed to produce IFN but produced MIP-1beta in response to NDV. We conclude that neutrophils fail to prevent viral infection by IFN production but probably possess alternative mechanisms, such as secreting MIP-1beta in response to viruses.

Cells, Cultured↗
PubMed2001

Induction of interleukin-8 in human neutrophils after MHC class II cross-linking with superantigens.

Neutrophils have been shown to express major histocompatibility complex class II (MHC II) after stimulation. However, reports concerning the functional effect of MCH II expression are still lacking. In our hands, granulocyte-monocyte colony-stimulating factor (GM-CSF) alone and in combination with interferon (IFN)-gamma, but not IFN-gamma or interleukin (IL)-3, induced a significant level of expression of human leukocyte antigen DR on neutrophils. The addition of staphylococcal enterotoxin E to neutrophils resulted in a significant increase in IL-8 production only after prestimulation with GM-CSF alone or in combination with IFN-gamma but had no effect on neutrophils preincubated with IFN-gamma alone or IL-3. Staphylococcal enterotoxin A, another bivalent superantigen, also stimulated production of IL-8 by preincubated polymorphonuclear neutrophils, whereas staphylococcal enterotoxin A mutants that are not able to cross-link MHC II molecules failed to induce IL-8 production. Taken together, our results clearly demonstrate that after induction of MHC II, neutrophils are able to respond to MHC II-specific stimulation. These findings support the ideas that the induced MHC II complex is completely functional and that neutrophils may be able to present antigens.

Enterotoxins↗
PubMed1999

Desensitization of melanoma cells to autocrine TGF-beta isoforms.

Previous studies have suggested that transforming growth factor-beta 1 (TGF-beta1) acts as an autocrine growth inhibitor on normal human melanocytes, while melanoma cells may not respond to this stimulus. The role of other TGF-beta isoforms such as TGF-beta2 and TGF-beta3 remained less well characterized. In the present study, the mRNA and protein levels of all three isoforms of TGF-beta were analyzed in a panel of human melanoma cell lines and in cultures of normal human melanocytes in vitro. Northern analysis showed that the degree of TGF-beta1, -beta2, -beta3 mRNA expression varied considerably in melanoma cells, whereas TGF-beta expression was very low in melanocytes. In melanoma cells, secreted amounts of TGF-beta1 and TGF-beta3 were found increased in comparison to normal melanocytes: 615 pg/ml vs. 118 pg/ml and 193 pg/ml vs. 30 pg/ml (mean values). In addition, low levels of TGF-beta2 were detected (mean value: 28 pg/ml). Although TGF-beta secretion increased, the proliferation of melanoma cells was found to be only moderately inhibited by TGF-beta isoforms, in contrast to its strong antiproliferative effect on normal human melanocytes: - 15%, -11%, and -18% vs. -52%, -46%, and -50% average inhibition at 0.5 ng/ml TGF-beta1, -beta2, and -beta3, respectively. The different efficacy of TGF-beta on melanocyte and melanoma cells was highly significant (P<0.0001); in addition, TGF-beta-dependent growth inhibition of melanoma cells from primary tumors vs. cells from metastases showed a trend for further decreased response for the metastatic populations (P< or = 0.075). Measurements of DNA synthesis revealed even more pronounced differences between melanocytes (-86%, -78%, and -80% inhibition, respectively, for TGF-beta1, -beta2, and -beta3) and melanoma cells (no inhibition). Our data show loss of responsiveness of melanoma cells to the growth-inhibitory function of TGF-beta isoforms but not of melanocytes. Although melanoma cells are not growth-inhibited by all three TGF-beta isoforms, they secrete significantly higher levels of TGF-beta, as compared to melanocytes. The reduced response indicates their escape from TGF-beta surveillance with ongoing tumor progression.

Cell Division↗
PubMed1997

Octreotide inhibition of flushing and colonic motor dysfunction in carcinoid syndrome.

OBJECTIVES: Previous studies showed increased plasma motilin and substance P concentrations and accelerated motor function in the small bowel and colon in patients with carcinoid diarrhea. Octreotide is beneficial in patients with carcinoid syndrome. Our hypothesis was that octreotide inhibits accelerated motility and gut neuropeptides in carcinoid syndrome. METHODS: In 12 patients with metastatic carcinoid syndrome, we investigated the effect of octreotide 50 microg s.c. t.i.d (n = 6) or placebo (n = 6) on postprandial symptoms, GI transit, colonic motility, and circulating levels of selected circulating peptides and amines. RESULTS: Octreotide reduced postprandial flushing (p = 0.03) but not pain. Octreotide significantly retarded overall colonic transit and proximal colonic emptying (p < 0.05); it tended to prolong small bowel transit time (p = 0.13) and to reduce postprandial colonic tone (p = 0.08) compared with placebo. Octreotide also reduced circulating levels of peptide YY, neurotensin, vasoactive intestinal polypeptide, and substance P but had no effect on plasma motilin, neuropeptide Y, calcitonin gene-related peptide, or histamine after meal ingestion. CONCLUSION: Octreotide ameliorates gut motor dysfunctions that characterize carcinoid diarrhea; the potential role of specific antagonism of serotonin, substance P, and vasoactive intestinal polypeptide alone or in combination with agents that inhibit their release in carcinoid diarrhea deserves further study.

Aged↗
PubMed1996

[Treatment of radiotherapy-induced gastroparesis with erythromycin].

HISTORY: A 75-year-old woman who had undergone a hysterectomy with adnexectomy followed by radiotherapy for endometrial carcinoma complained of postprandial nausea with vomiting after eating solid foods and of cramp-like abdominal pain, but her appetite was good. She had lost 25 kg in weight over 13 months. EXAMINATION: Physical examination, laboratory tests, radiology and gastroscopy were unremarkable. Gastric scintigraphy showed abnormally prolonged emptying. TREATMENT AND COURSE: Nausea and vomiting stopped at once after erythromycin (a motilin agonist) had been administered. It was at first given intravenously after meals (50 mg three times daily for 5 days), then orally for 10 weeks (250 mg three times daily before meals). Subsequent examination revealed normal gastric emptying. The symptoms did not recur after erythromycin had been discontinued. CONCLUSION: Erythromycin is an effective drug against gastroparesis caused by radiotherapy, because it acts even when the enteric nerves are damaged.

Aged↗
PubMed1994

[Irritable colon syndrome].

The irritable bowel syndrome (IBS) is a common chronic functional disorder. Although its cause is unclear, a multifactorial etiology has been hypothesized with several putative pathophysiological mechanisms which may interact. These include abnormal intestinal motor function, abnormal visceral perception, psychosocial factors and luminal factors that irritate the small bowel and colon. A positive diagnosis should be made from an accurate history and physical examination and requires confirmation by exclusion of structural, metabolic and infectious processes that may result in similar clinical presentations. The IBS can be classified on the basis of its broad clinical spectrum of severity and variable patterns of dominant symptoms. Such a classification permits an appropriately graduated treatment approach that includes patient education, dietary adjustment, psychotherapeutic and behavioral techniques, as well as a symptom-orientated pharmaco- and psychopharmacotherapy. The majority of patients has mild symptoms and requires no specific treatment besides careful education and reassurance and dietary adjustment. For moderate symptom severity, additional psychotherapy and behavior techniques are indicated, which should be combined with pharmacotherapy targeted at the presumed pathomechanism. For severe symptoms, physician-based behavior modification and psychopharmacological agents may be needed.

Behavior Therapy↗
PubMed1993

[The synthetic somatostatin analog octreotide: effect on interdigestive pancreas secretion and gastrointestinal motility in man].

The aim of the present study was to determine the effects of a therapeutical dose of the long-acting cyclic somatostatin analogue octreotide (SMS 201-995) on cyclical interdigestive small intestinal motor function and exocrine pancreatic secretion in humans. Five fasting healthy subjects swallowed a gastroduodenal multi-lumen tube assembly and received continuous infusions of saline and octreotide (720 ng/kg/hr) for at least one interdigestive motor cycle or two hours. Upper gastrointestinal motility was recorded continuously by standard manometry. Duodenal chymotrypsin outputs were measured at 15 minutes intervals using polyethylene glycol as a dilution marker. Octreotide significantly decreased the length of the interdigestive motor cycle to one third of the control period (p < 0.01). Phase II proportion was reduced to less than 5% of the cycle length (controls: 66%; p < 0.01). The propagation velocity of octreotide-induced motor activity fronts was significantly slower compared with migrating motor complexes during the control period (controls: 6.8 +/- 0.4 cm/min, octreotide: 2.3 +/- 0.4 cm/min; p < 0.05). Overall duodenal chymotrypsin output was markedly inhibited by octreotide (5% of controls; p < 0.01). Moreover, during octreotide administration coupling between interdigestive motor activity and pancreatic exocrine enzyme secretion was disrupted. In conclusion short administration of a therapeutical dose of octreotide exerts similar effects on upper intestinal interdigestive human motor secretory parameters as naturally occurring molecular forms of somatostatin at pharmacological doses.

Adult↗
PubMed1993

Effects of serotonin on rat ileocolonic transit and fluid transfer in vivo: possible mechanisms of action.

The aim was to investigate the action of serotonin (5HT) on function of the ileocolonic junction (ICJ) in vivo. In anaesthetised rats, models were developed to study the effects of intra-aortic (ia) serotonin on ileocolonic and colonic transit, and the effects on transit of a number of 5HT receptor antagonists. In the first series of experiments, a bolus of saline labelled with 99mTc DTPA was instilled 20 cm proximal to the ICJ and transit was assessed three hours later by the geometric centre of the spread of isotope. In the second series, similar techniques were used on the postcaecal colon and transit assessed two hours later. In the third series of experiments, the effects of ia 5HT on ileal net fluid flux was evaluated by standard perfusion experiments with 14C polyethylene glycol (PEG) 4000 as a non-absorbable marker in rat plasma-like electrolyte solution. Compared with ia saline, 5HT accelerated ICJ transit significantly (p < 0.05). This acceleration was comparable with the effect of ia bethanechol. The effects of 5HT on ICJ transit were inhibited by the intraperitoneal (ip) infusion of atropine, the 5HT receptor antagonists, methysergide, ketanserin, zacopride, and the 5HT4 agonist, SC53116. Methysergide, zacopride, and SC53116 given with ia 5HT slowed ICJ transit to rates below those of ia saline alone. When these same agents were given together with ia saline, the ICJ transit was not significantly altered. Serotonin, at the dose that accelerated ICJ transit, did not significantly alter colonic transit or ileal fluid transport. In conclusion, 5HT is a potent pharmacological stimulant of transit across the rat ICJ in vivo; the action of 5HT is mediated partly through muscarinic neurones and several 5HT receptor subtypes.

Animals↗
PubMed1992

Somatostatin 28 and coupling of human interdigestive intestinal motility and pancreatic secretion.

To determine the effects of small increases in somatostatin 28 plasma concentrations on human interdigestive gastrointestinal motility and pancreatic secretion, six fasting volunteers were intubated with gastroduodenal multilumen tubes and motility and pancreatic enzyme secretion were measured. Subjects received intravenous NaCl and somatostatin 28 at 11 and 44 pmol.kg-1.h-1 for 120 minutes or at least one interdigestive cycle. The two doses increased plasma somatostatin 28 levels within the physiological or into the supraphysiological range, respectively. Somatostatin 28 at 11 and 44 pmol.kg-1.h-1 decreased the length of the interdigestive motility cycle by 50% and 67% compared with controls, respectively (both P less than 0.002). Propagation velocity of the migrating motor complex (P less than 0.01) and plasma motilin were decreased (P less than 0.01). The smaller and larger dose decreased pancreatic enzyme outputs by 50% and 65%, respectively (P less than 0.005), but with the smaller dose, phase III-associated enzyme outputs were greater than phase I outputs. These findings suggest that small changes in somatostatin 28 plasma concentrations modulate human interdigestive motility and pancreatic enzyme output while coupling of motor and secretory events is preserved.

Adult↗
PubMed1987

Biorhythmic changes of plasma histamine levels in healthy volunteers.

The plasma histamine levels were reported to increase in early hours of the morning in asthmatic patients. It was supposed that this phenomenon would also be observed in normal volunteers. In this study using twelve normal healthy volunteers the plasma histamine levels were examined in a pharmacokinetic manner. It could be shown that plasma histamine levels flow biorhythmic changes with 3 maxima and 3 minima. The acrophases of the maxima are 12.77 +/- 0.61, 19.33 +/- 0.78 and 5.42 +/- 1.83 h. The most important rise in plasma histamine levels was found in the early hours of the morning representing about 55% of the total histamine available in plasma.

Adult↗
PubMed1985

Intranasal thyrotrophin releasing hormone is a potent stimulus for TSH release in man (comparison with intravenous and oral TRH).

Intranasally administered TRH was tested and compared to i.v. and oral TRH in respect to its efficacy of TSH stimulation and thereby the stimulation of thyroid reserve. TSH release after nasal application is as prompt as after the i.v. route, reaching a peak at 20 to 30 min. After that, however, compared to the i.v. administration its stimulatory effect is prolonged, lasting over 3 h. At the dose used in this study the peak TSH response after intranasal TRH administration was 14.7 +/- 1.6 mU/l compared to 8.4 +/- 1.4 and 23.1 +/- 4.4 mU/l after i.v. and oral administration respectively (P less than 0.005). Intranasal application of TRH is as potent as i.v. or oral TRH for the stimulation of thyroid reserve. At 3 h a marked increase of T3 and a smaller elevation of FT4 is observed (delta T3 = 48.4%, delta FT4 = 31.6%). The nasal peptide was well tolerated locally and systemic side effects were comparable to those of i.v. TRH. This form of application offers a practical advantage by avoiding intravenous injections. Its diagnostic potential in investigation of thyroid disease and its possible therapeutic application have yet to be elucidated.

Administration, Intranasal↗
PubMed1984

[The effect pf antacids on the tissue histamine and prostaglandin (PGE2) content of the gastric mucosa].

Stimulation tests (pentagastrin) induced significant changes in tissue histamine levels in the gastric mucosa within 30 minutes. Acid secretion and a decrease of histamine after application of antacids containing calcium could not be observed in our study; neither was application of antacids over a period of eight days followed by a change in gastric mucosal tissue histamine concentrations. Patients under non-steroidal antiphlogistic medication showed diminished histamine levels. Administration of antacids did not produce changes in histamine levels, but induced a rise of PGE2 levels in the fundal and corpus area of the stomach. This may be due to a cytoprotective effect of antacids containing calcium on the gastric mucosa.

Adult↗
PubMed1981

Influence of the LH-RH analogue buserelin on cyclic ovarian function and on endometrium. A new approach to fertility control?

The long-acting stimulatory luteinizing hormone - releasing hormone analogue D-Ser(TBU)6-EA10-LH-RH (buserelin) was administered intranasally once daily in a dose of 400 mcg to 24 normally ovulating women and to 4 women with pre-existing endocrine dysregulation. Ovulation was inhibited in 136 out of 156 treatment months. In 20 treatment months, progesterone values temporarily increased indicating luteinization of follicles or ovulation with defective corpus luteum function. Estradiol secretion showed a tendency to lower values as treatment progressed but individually indicated follicle maturation until the end of the observed medication period. Bleeding pattern ranged from menses-like bleeding in regular as well as irregular intervals to amenorrhea. The morphological findings of 31 endometrial biopsies of 20 volunteers ranged from atrophy (n = 4) to proliferation (n = 25) with early signs of hyperplasia as well as early secretory transformation (n = 2). The morphological alterations indicate that unopposed estrogen stimulation of the endometrium is the main problem of long-term contraception with the dose schedule of buserelin used.

Adolescent↗