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A Gasser

Publications and source records attributed to A Gasser.

At least 19 recordsLinked to original sources
PubMed2007

Regulation of calcium signalling by adenine-based second messengers.

cADPR [cyclic ADPR (ADP-ribose)], NAADP (nicotinic acid-adenine dinucleotide phosphate) and ADPR belong to the family of adenine-containing second messengers. They are metabolically related and are all involved in the regulation of cellular Ca(2+) homoeostasis. Activation of specific plasma membrane receptors is connected to cADPR formation in many cell types and tissues. In contrast receptor-mediated formation of NAADP and ADPR has been shown only in a few selected cellular systems. The intracellular Ca(2+) channel triggered by cADPR is the RyR (ryanodine receptor); in the case of NAADP, both activation of RyR and a novel Ca(2+) channel have been proposed. In contrast, ADPR opens the non-specific cation channel TRPM2 [TRP (transient receptor potential) melastatin 2] that belongs to the TRP family of ion channels.

Adenine↗
PubMed2006

Cellular effects and metabolic stability of N1-cyclic inosine diphosphoribose and its derivatives.

BACKGROUND AND PURPOSE: Recently, a number of mimics of the second messenger cyclic ADP-ribose (cADPR) with replacement of adenosine by inosine were introduced. In addition, various alterations in the molecule ranging from substitutions at C8 of the base up to full replacement of the ribose moieties still retained biological activity. However, nothing is known about the metabolic stability and cellular effects of these novel analogues. EXPERIMENTAL APPROACH: cADPR and the inosine-based analogues were incubated with CD38, ADP-ribosyl cyclase and NAD-glycohydrolase and metabolism was analysed by RP-HPLC. Furthermore, the effect of the analogues on cytokine expression and proliferation was investigated in primary T-lymphocytes and T-lymphoma cells. KEY RESULTS: Incubation of cADPR with CD38 resulted in degradation to adenosine diphosphoribose. ADP-ribosyl cyclase weakly catabolised cADPR whereas NAD-glycohydrolase showed no such activity. In contrast, N1-cyclic inosine 5'-diphosphoribose (N1-cIDPR) was not hydrolyzed by CD38. Three additional N1-cIDPR analogues showed a similar stability. Proliferation of Jurkat T-lymphoma cells was inhibited by N1-cIDPR, N1-[(phosphoryl-O-ethoxy)-methyl]-N9-[(phosphoryl-O-ethoxy)-methyl]-hypoxanthine-cyclic pyrophosphate (N1-cIDP-DE) and N1-ethoxymethyl-cIDPR (N1-cIDPRE). In contrast, in primary T cells neither proliferation nor cytokine expression was affected by these compounds. CONCLUSIONS AND IMPLICATIONS: The metabolic stability of N1-cIDPR and its analogues provides an advantage for the development of novel pharmaceutical compounds interfering with cADPR mediated Ca2+ signalling pathways. The differential effects of N1-cIDPR and N1-cIDPRE on proliferation and cytokine expression in primary T cells versus T-lymphoma cells may constitute a starting point for novel anti-tumor drugs.

ADP-ribosyl Cyclase↗
PubMed2001

Interaction of HSV-1 infected peripheral blood mononuclear cells with cultured dermal microvascular endothelial cells: a potential model for the pathogenesis of HSV-1 induced erythema multiforme.

The effect of herpes virus infection on human dermal microvascular endothelial cells and herpes-virus-1-infected peripheral blood mononuclear cells on human dermal microvascular endothelial cells was studied as a model of herpes-associated erythema multiforme. After infection of human dermal microvascular endothelial cells with native herpes virus and overnight culture, 60%--90% of human dermal microvascular endothelial cells showed cytopathic effects. HLA class I molecules and CD31 (PECAM-1) surface expression in herpes-virus-infected endothelial cells were substantially downregulated, whereas CD54 (ICAM-1) remained unchanged. Cocultivation with herpes-virus-1-infected peripheral blood mononuclear cells left characteristic plaques on the human dermal microvascular endothelial cell monolayer; however, very few human dermal microvascular endothelial cells (1%--3%) were infected. Adhesion molecule expression of human dermal microvascular endothelial cells cocultivated with herpes-virus-infected peripheral blood mononuclear cells demonstrated a 5-fold increase in CD54 expression, a 2-fold increase in HLA class I expression, but no change of CD31 by fluorescence-activated cell sorter analysis. Incubation of human dermal microvascular endothelial cells with ultraviolet-C irradiated herpes-virus-infected peripheral blood mononuclear cells had no effect on morphology or adhesion molecule expression levels. Changes of adhesion molecule expression by direct infection or cocultivation with peripheral blood mononuclear cells (with native and ultraviolet-C inactivated herpes virus infection) were also documented at the mRNA level. Adhesion assays demonstrated an increased binding of herpes-virus-infected peripheral blood mononuclear cells versus noninfected peripheral blood mononuclear cells to noninfected human dermal microvascular endothelial cells. Our results suggest that incubation of herpes-virus-infected peripheral blood mononuclear cells with human dermal microvascular endothelial cells induces significant upregulation of CD54 and major histocompatibility complex class I molecules in the surrounding noninfected human dermal microvascular endothelial cells, which is associated with an increased binding of peripheral blood mononuclear cells. Our in vitro findings may serve as a model for herpes-associated erythema multiforme possibly explaining the dermal inflammatory reaction seen in that condition.

Antigens, Surface↗
PubMed1999

Generation of multinucleated giant cells in vitro by culture of human monocytes with Mycobacterium bovis BCG in combination with cytokine-containing supernatants.

Multinucleated giant cells (MGC), a characteristic feature of tuberculous granulomas, form by fusion of monocytes or macrophages, but little is known about the mechanism of the fusion process itself. Several studies report an indirect effect of mycobacteria, i.e., induction of a soluble lymphocyte-derived fusion factor following stimulation by mycobacteria or mycobacterial products. The aim of our study was to determine whether contact with mycobacteria can induce MGC formation from human monocytes in vitro. Stimulation of monocytes with Mycobacterium bovis bacillus Calmette-Guérin (BCG) in combination with cytokine-containing supernatants of herpesvirus saimiri-transformed human T-cell clones (T-SN) led to MGC formation with fusion rates of about 27%. In contrast, stimulation with one component alone induced only low fusion rates of up to 10%. Heat-killed BCG in combination with T-SN induced monocyte fusion to the same extent as live mycobacteria. BCG culture supernatant, BCG lysate, or inert particles in combination with T-SN did not induce MGC formation. Experiments using transwell plates containing a semipermeable membrane revealed that induction of the fusion process is dependent on direct contact of monocytes and mycobacteria. MGC formation induced by BCG plus T-SN could be inhibited by addition of monoclonal antibodies to gamma interferon (but not tumor necrosis factor alpha) as well as to the beta chain (CD18) of beta2-integrins. These results demonstrate that contact with mycobacteria in combination with cytokine-containing supernatants is able to induce human monocytes to form MGC and that membrane-bound molecules of mycobacteria and monocytes are involved in the fusion process.

Adult↗
PubMed1997

Formation of multinucleated giant cells in vitro is dependent on the stage of monocyte to macrophage maturation.

Multinucleated giant cells (MGC) are a common feature of granulomas that develop during various inflammatory reactions. MGC originate from fusion of monocytes or macrophages, but the exact mechanism of their generation is still unclear. In the present study, we investigated the influence of monocyte to macrophage maturation on the ability of human monocytes/macrophages to fuse with each other. MGC were generated in vitro by stimulation of human peripheral blood monocytes with cytokine containing supernatants. With freshly isolated monocytes, fusion rates of up to 90% were obtained. When monocyte to macrophage maturation was induced by culturing the cells in human serum, fusion rates gradually decreased with advancing time of the preceding culture (corresponding to the stage of differentiation) and almost no MGC formation could be obtained with 8-day-old macrophages. In contrast, fusion rates did not decrease when monocytes had been cultured under serum free conditions before stimulation. When freshly isolated monocytes were added to 1-week cultured macrophages, which had been membrane-labeled with a fluorochrome, fusion between the two populations could be induced. Because the ability for intracellular killing of certain pathogens is reduced in macrophages, fusion with monocytes (newly arriving at the site of inflammation) may represent an attempt to restore this capacity.

Cell Differentiation↗
PubMed1995

Curative treatment of clinical stage II endometrial carcinoma.

In a retrospective study of 54 patients we compared three treatment policies of clinical stage II endometrial carcinoma: One group of patients (n = 29) was surgically staged with histological examination made at surgery and treated by abdominal total hysterectomy with bilateral salpingo-oophorectomy. In case of cervical infiltration by tumour, a pelvic node sampling was added. The second group was treated by radical hysterectomy (n = 9) and the third group of patients (n = 16) was treated by abdominal total hysterectomy with bilateral oophorectomy only. The median follow-up time was 68 months. The overall five year-survival was 64%. The overall five year-survival rates according to surgical procedure were not significantly different. The survival curves were significantly different from each other as were those according to surgical stage and age. In a multivariant analysis stage, grading and age proved to have an independent relation with the survival rate whereas type of surgical procedure, depth of myometrial infiltration and type of radiotherapy had no influence on survival. Intraoperative histological staging allows adaption of treatment to the true stage, thus minimising treatment-related morbidity.

Adult↗
PubMed1993

[Urothelial cancer of the upper urinary tract].

Uretero-nephrectomy with bladder cuff was performed in 61 patients with renal pelvis and ureter carcinoma between 1982 and 1987. A retrospective study was done on 54 patients, with a mean follow up of 56.9 months. The 5-year survival was 61.6%. The average age was 68.8 years with a male-to-female ratio of 1.7:1. Macrohaematuria was the most frequent symptom, occurring in 77.7% of the patients. In 92.5% of the urothelial tumours the diagnosis was confirmed by intravenous pyelogram (IVP) and retrograde pyelography. Between grade G1 and G3 and stage pTa and pT3-4 a statistically significant difference (P < 0.05) in the 5-year survival rate could be seen, as expected.

Adult↗
PubMed1992

Prevalence of the Rhesus-negative phenotype in Caucasian patients with small-cell lung cancer (SCLC).

We report that the Rhesus (Rh)-negative phenotype is more prevalent in patients with small-cell lung cancer (SCLC) than in the normal Caucasian population (SCLC: 25% Rh-negative vs. 15% expected, p less than 0.0001). This finding has been validated for a Central and a Northern European population (Switzerland and UK). In contrast, the Rh-negative phenotype is no more frequent in non-small-cell lung cancer patients or in heavy smokers with coronary heart disease than in the general population. There was a normal distribution of the ABO blood group phenotype in all patients studied. Whilst the significance of this observation is unclear, we hypothesize that a genetic predisposition to the development of SCLC may be linked to a hitherto unidentified gene on chromosome 1p near the Rh locus. Our observation may perhaps allow further progress to be made in understanding genetic mechanisms of SCLC carcinogenesis.

ABO Blood-Group System↗
PubMed1992

[Staging and prognosis of colorectal carcinoma].

Three different systems in staging colorectal cancer (TNM3, ACPS, TNM4/Dukes) have been compared in 318 patients treated at some stage of their disease at Berne University Hospital. Simultaneously, the role of some prognostic factors for survival and relapse has been analyzed. The estimated 5 years' survival rate for all patients is 42%. After complete removal of the tumor 49% of patients relapsed. In a multivariate analysis the stage, age above 80 years and the site of the primary tumor have an influence on survival and relapse. Blood transfusions had no effect on either in this analysis. The concordance of the three staging systems is good and the resultant survival curves are similar. TNM3 puts some patients with a bad prognosis into stage I. ACPS classifies patients with residual tumor after surgery with patients with distal metastasis. It has no further advantages over TNM4. TNM4 seems at present to be the best staging system. It incorporates the advantages of the well-known Dukes classification and, with possible refinements, has the qualities to be used as a standard method.

Adult↗
PubMed1992

Pheochromocytoma of the urinary bladder.

A case of a pheochromocytoma of the urinary bladder is reported which was treated preoperatively with alpha-receptor-blocking agents. The tumor was operated transurethrally, followed by partial cystectomy.

Combined Modality Therapy↗
PubMed1991

[Vulvar cancer. Bern university gynecologic clinic patients treated 1978 to 1987].

Between 1978 and 1987, 44 women with primary invasive carcinoma of the vulva were treated. The mean age of the patients was 69 years (24-91). The predominant histologic type was squamous cell carcinoma. Thirteen radical vulvectomies were performed. Various other vulvar operative procedures were performed on 27 cases and were followed up with or without radiation therapy. The 5-year survival rate was 80% in stage T1 patients, 58% in T2 and 40% in T3. Patients with negative lymph nodes had a survival rate of 79% after 5 years and those with positive nodes a survival rate of 40%. A modified radical vulvectomy was performed: to the Pary-Jones incision we use an additional groin incision. The advantage is better wound healing as compared to Way's technique.

Adult↗
PubMed1990

Prostate-specific antigen in prostatic carcinoma.

To evaluate the clinical and prognostic value of prostate-specific antigen (PSA) for the detection of tumor and tumor growth after therapy, 520 sera from 246 patients with prostatic carcinoma, 990 sera from patients with BPH, and 1,488 sera from patients with other urological diseases were analyzed. The values ranged from 0.1 to 1,828.9 ng/ml. 51% of all values were about 2.5 ng/ml, and 76.8% of all values about 10 ng/ml. The commercial recommendation for the cutoff values is 2.5 ng/ml (IBL, FRG). In patients with benign prostatic hypertrophy this cutoff means 61% false-positive results, which makes the test highly sensitive but unspecific. In prostatic carcinoma patients this borderline means a false-negative result in 9.75% (24 of 246). By determining the cutoff at 10 ng/ml in our series, a false-negative result appeared in 14.6%. Therefore a plea is made for the 10-ng/ml cutoff. In follow-up studies a marked decline in PSA values after transurethral resection or antiandrogen therapy (orchiectomy/Zoladex/ICI/flutamide, Essex). Generally, the greater the PSA levels the more advanced the stage of disease. These data suggest that PSA may be a useful adjuvant marker for monitoring tumor growth in patients with regionally confined tumor.

Aged↗
PubMed1990

[Clinical aspects, follow-up and therapy of benign tumors of the epididymis and para-testicular tissue].

Between July 1982 and July 1988, 15 patients were operated on because of a paratesticular solid tumor. In 10 of the 15 tumors the testis could be preserved by excision or enucleation of the tumor because the frozen section showed an adenomatoid tumor. None of the patients show tumor recurrence after a follow-up of 25.3 months. If the frozen section is found to be benign, a plea is made that the tumor be excised or enucleated without semicastration.

Adenoma↗
PubMed1988

[Swiss interregional epidemiologic study of the risk of cancer in the contralateral breast].

This epidemiologic investigation in three Swiss regions (Geneva, St. Gall-Appenzell, Vaud) included 5,193 women diagnosed as having a first primary breast cancer. The patients were followed up for ten years (the observation totalled 24,994 women-years). Overall, these results confirmed that the relative risk of a second breast cancer was greatly increased during the first year following the primary diagnosis, but this was largely due to simultaneously discovered contralateral tumours. Beyond the first year of follow-up, the relative risk of a second tumour was lower but still significantly greater than unity. No significant diminution of the excess risk was observed in the first 10 years of follow-up. Relative risk of a second breast cancer was generally higher before age 50, independently of the latency. The relative risk of a second breast cancer differed significantly from one region to another, possibly due to specific techniques of registration.

Adult↗
PubMed1985

[Multidisciplinary study of the prolonged treatment of involution osteoporosis using sodium fluoride with calcium, phosphate and vitamin D].

A multidisciplinary study on the prolonged treatment of involution osteoporosis with fluoride was performed on a homogeneous population of 31 women aged 51 to 75 years (mean 64 years). The selection criteria were the following: significant backache, vertebral compression fractures on X-rays, bone biopsy evidence of osteoporosis, and absence of other risk factors after a complete workup. The patients were treated for a period of 3 to 6 years (mean 4 years) with daily doses of 30 mg (10 mg 3 times) fluorides ion associated during the last 3 years with 500 mg calcium twice daily, 750 mg phosphate and 1000 units vitamin D daily. The study demonstrated a favourable effect of the treatment on the backache and that it was well tolerated in the majority of cases, the side effects being intermittent osteo-articular pains of the lower extremities due to the fluoride in 9 patients, and gastric intolerance to the phosphate in 7. X-ray follow-up showed slowing of the vertebral compressions after the first year of treatment, but no effect on fractures of the extremities. There was no evidence of alterations in parameters of mineral and bone metabolism, and in endocrine, hepatic, renal or hematological assays. Histomorphometric and biophysical examination of biopsies indicated that, although there was no significant increase in the quantity of mineralized bone under the treatment, there was a very significant improvement in the crystallinity of the mineral substance, thus enhancing the quality of the bone tissue and its resistance to pressure. This study is the first in which a catamnesis of the patients was undertaken, 28 of them having received a clinical and radiological examination 2 years after the end of therapy: a favourable evolution was observed in most of the cases, both in those patients treated for a period of 3 years and in those whose treatment had lasted for a longer period.

Aged↗
PubMed1980

Production of glycolate by oxidation of the 1,2-dihydroxyethyl-thamin-diphosphate intermediate of transketolase with hexacyanoferrate(III) or H2O2.

In the presence of hexacyanoferrate(III), or other suitable oxidants, transketolase catalyzes the oxidative cleavage of its donor substrates xylulose 5-phosphate or fructose 6-phosphate into glycolate and glyceraldehyde 3-phosphate or erythrose 4-phosphate, respectively. Two moles of hexacyanoferrate(III) are reduced per mole of oxidatively cleaved donor substrate. In analogy to the oxidative trapping of carbanion intermediates of other enzymes [Healy, M. J. & Christen, P. (1973) Biochemistry, 12, 35-41], the kinetic features of the reaction indicate that the 1,2-dihydroxyethylthiamin diphosphate intermediate is the oxidation-susceptible species. The molecular activity for the oxidative cleavage of fructose 6-phosphate at a hexacyanoferrate(III) concentration of 0.5 mM is 0.2% of that for the normal transfer reaction with erythrose 4-phosphate as acceptor substrate. Glycolate is also produced with H2O2 as oxidant; however, the reaction is at least two orders of magnitude slower than with hexacyanoferrate(III).

Ferricyanides↗
PubMed1979

The clinical measurement of urinary total hydroxyproline excretion.

The effect of dietary control on the day-to-day variation in total hydroxyproline excretion has been examined in two studies. In the first, a normal volunteer ate a controlled diet containing varying gelatin supplements for several weeks. In the second, the effect of removing hydroxyproline-containing foods from the diets of 8 volunteers was examined. Both studies confirm that the day-to-day variation in total hydroxyproline excretion falls when the gelatin content of the diet is decreased, whether the results are expressed as total hydroxyproline excretion rate or as the total hydroxyproline: creatinine ratio. This fall in variation takes place within 24 h of dietary control beginning and therefore longer periods of dietary restrictions to achieve optimum precision in the measurement of total hydroxyproline are unnecessary. For some analytical methods, results are better expressed as the ratio total hydroxyproline:creatinine than as the total hydroxyproline excretion rate.

Adult↗