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PubMed1991

[Effects of buserelin presurgical treatment on vascularity in the sub-serosal interstitial tissue of the uterus and operative blood loss at hysterectomy in women with uterine leiomyoma and adenomyosis].

We examined 194 cases of uterine leiomyoma and adenomyosis who received total abdominal hysterectomy, in order to compare the effect of presurgical medical treatment such as with Buserelin, Danazol and Pill, on operative blood loss with non-treated group. The operative blood loss was 314.0 +/- 177.2 ml (mean +/- SD) in the control group (n = 145), 211.2 +/- 64.1 ml in the Buserelin-treated group (n = 26), 276.8 +/- 110.7 ml in the Danazol-treated group (n = 10), and 396.6 +/- 213.1 ml in the Pill-treated group (n = 13). The operative blood loss in the Buserelin-treated group was significantly lower than in the control group (p less than 0.01) and in the Pill-treated group (p less than 0.05). After considering the pathology of the uterus, the uterine size, and the level of expertise of the surgeon, the operative blood loss in the Buserelin-treated group was significantly lower than in the control group. We measured the capillary space, small arteries and veins in the sub-serosal interstitial tissue of the uterus, and observed that the vascular space decreased significantly (p less than 0.01) in the Buserelin-treated group compared to the control group. From these facts it may be concluded that Buserelin presurgical treatment reduces the operative blood loss at hysterectomy, and it seems very likely that the decrease in vascularity may play an important role.

Blood Loss, Surgical↗
PubMed1991

Molecular cloning of the mouse mast cell protease-5 gene. A novel secretory granule protease expressed early in the differentiation of serosal mast cells.

cDNAs were isolated that encode mouse mast cell protease-5 (MMCP-5), an approximately 30,000 Mr serine protease stored in the secretory granules of serosal mast cells (SMC) and Kirsten sarcoma virus-immortalized mast cells. Based on the deduced amino acid sequences of these cDNAs, MMCP-5 is synthesized as a 247-amino acid preproenzyme composed of a novel 19-residue hydrophobic signal peptide, a Gly-Glu activation peptide not present in other mast cell chymases, and a 226-amino acid protein that represents the mature enzyme. MMCP-5 possesses a unique Asn residue in the substrate binding cleft at residue 176 and is highly basically charged. The MMCP-5 gene was isolated, sequenced, and found to belong to a distinct subset of chymase genes. Allelic variations of the MMCP-5 gene were also detected. MMCP-5 is expressed in bone marrow-derived mast cells (BMMC), Kirsten sarcoma virus-immortalized mast cells, and SMC, but not in gastrointestinal mucosal mast cells of helminth-infected mice. The abundant levels of MMCP-5 mRNA in immature BMMC indicate that this chymase is expressed relatively early during the differentiation of mast cells. MMCP-5 is the first chymase to be molecularly cloned from progenitor mast cells and is also the first chymase shown to be expressed preferentially in the SMC subclass.

Amino Acid Sequence↗
PubMed1991

Prognostic significance of serosal invasion in carcinoma of the stomach.

Two hundred and seventy-seven patients with advanced carcinoma of the stomach invading the serosa were studied with regard to the relationship between the length of the serosal invasion (LSI) and prognosis, with a division made between expanding and infiltrative types of tumors. Among patients with expanding types of tumors, five year survival rates were 40 per cent in patients with LSI less than 4.0 centimeters, 33 per cent in patients with LSI 4.1 to 6.0 centimeters and 13.0 per cent in patients with LSI more than 6.0 centimeters. Among those patients with infiltrative types of tumors, those with less than 2.0 centimeters of LSI had a better prognosis (five year survival rate of 53 per cent), whereas those patients with a LSI more than 2.0 centimeters had a very poor prognosis (five year survival rate of less than 20 per cent) and the significant LSI on prognosis was found to be 2.0 centimeters. Involvement of the lymph node and metastasis to the liver were not affected by LSI, whereas the rates of peritoneal dissemination and direct invasion to neighboring organs increased with an increase in LSI. Knowledge of these factors facilitates the planning of postoperative treatment.

Follow-Up Studies↗
PubMed1991

Modification of low density lipoproteins by secretory granules of rat serosal mast cells.

When low density lipoprotein (LDL) is incubated with granules isolated from rat serosal mast cells, a fraction of LDL is bound to the granule heparin proteoglycan. If incubation is continued at 37 degrees C, the bound LDL, but not the unbound LDL, is degraded by granule neutral proteases. In the early stage of incubation, all the granule-bound LDL can be released by 0.3 M NaCl (the "salt-sensitive" fraction of LDL). With time, an increasing proportion of the granule-bound LDL requires 0.5 M NaCl for release (the "salt-resistant" fraction of LDL). Chemical analysis showed that, on average, 20% of the apolipoprotein B LDL was lost from the salt-sensitive fraction and 60% from the salt-resistant fraction, without any change in the composition of the lipid portion. Electron microscopic analysis disclosed large fused particles of LDL (diameters up to 100 nm) in the highly proteolyzed salt-resistant fraction, but no fused particles could be found in the less proteolyzed salt-sensitive fraction. We conclude that both binding and extensive degradation of LDL by mast cell granules is required for fusion of LDL particles on the granule surface. As compared with native LDL, the mast cell granule-modified LDL particles exhibit (i) increased particle size, (ii) selective loss of protein (apoB), (iii) a decrease in hydrated density, and (iv) stronger ionic interaction between apoB and heparin proteoglycan. The particles resemble the extracellular lipid droplets found in atherosclerotic lesions of both man and animals. Modification of LDL by mast cells may therefore provide a model of how these lipid structures are formed.

Animals↗
PubMed1990

Mast cell heterogeneity. Differential synthesis and expression of glycosphingolipids by mouse serosal mast cells as compared to IL-3-dependent bone marrow culture-derived mast cells before or after coculture with 3T3 fibroblasts.

The synthesis and intracellular expression of glycosphingolipids by mouse serosal mast cells (SMC) have been characterized by radiolabeling and TLC and by immunodetection in situ. Chromatographic analysis of purified glycosphingolipids from SMC intrinsically labeled with [14C]galactose and [14C]glucosamine hydrochloride revealed the predominant synthesis of only the simplest neutral glycosphingolipid and ganglioside, glucosylceramide and ganglioside GM3, respectively. Intracellular indirect immunofluorescence staining of permeabilized SMC demonstrated the absence of the more complex neutral glycosphingolipids lactosylceramide, globotriosylceramide, globotetraosylceramide, and globopentaosylceramide, the absence of ganglioside GM1, and the presence of ganglioside GM3. By contrast, permeabilized mouse IL-3-dependent bone marrow culture-derived mast cells (BMMC) and mast cells recovered after 21 days of coculture of BMMC with mouse 3T3 fibroblasts expressed lactosylceramide, globotriosylceramide, globotetraosylceramide, ganglioside GM1, and ganglioside GM3, but not globopentaosylceramide intracellularly as determined by immunofluorescence. The findings indicate a loss of biosynthetic capacity and epitope maintenance for glycosphingolipids with in vivo differentiation of SMC from IL-3-dependent BMMC progenitors. Thus, although mast cells derived after coculture of these progenitors for 21 days with fibroblasts assume multiple SMC-like properties in terms of their histochemical staining and their secretory granule proteoglycan and neutral protease constituents, they do not lose the ability to express complex glycosphingolipids. The finding that glycosphingolipid composition does not change coordinately with other secretory granule markers defines a new stage of mouse mast cell development between the BMMC and SMC and provides evidence that mast cell development is more complex than previously appreciated.

Animals↗
PubMed1990

Cleavage of a rat serosal mast cell membrane component during degranulation mediated by chymase, a secretory granule protease.

Exogenous addition of purified chymase, a rat serosal mast cell (RSMC) chymotryptic enzyme, results in RSMC degranulation at 37 degrees, but not at 1 degree. Chymase can cause an active site-dependent inducing event at 1 degree such that RSMC degranulation occurs if the cells are later incubated at 37 degrees. RSMC exposed to chymase or other stimuli were surface radiolabelled using 125I and Iodo-Gen, solubilized with 1% Nonidet-40, and the resulting 25,000 g supernatants analysed by SDS-PAGE and autoradiography. A 125I-labelled RSMC membrane protein of approximate 90,000 MW decreased upon exposure to either chymase or alpha-chymotrypsin (alpha-CT) for 5 min at 37 degrees or to chymase for 60 min at 1 degree. Exposure of RSMC to the secretagogues ionophore A23187, compound 48/80, and anti-IgE for 5 min at 37 degrees resulted in beta-hexosaminidase (a secretory granule enzyme) release, but did not cause a detectable change in the 90,000 MW surface-labelled protein. Lima bean trypsin inhibitor, which inhibits both the esterase and RSMC degranulation activities of chymase and alpha-CT, prevented the disappearance of the 125I-labelled 90,000 MW band when added with chymase or alpha-CT. Exposure of RSMC to chymase at 1 degree for 0-10 min, prior to addition of LBTI, led to a progressive disappearance of the 90,000 MW band, which corresponded to the kinetics of priming for subsequent RSMC degranulation at 37 degrees. When RSMC were exposed to trypsin (2.5 micrograms/ml) for 0-120 min at 1 degree, a progressive disappearance of the 90,000 MW band occurred, in association with a loss of sensitivity to subsequent activation by chymase at 37 degrees. The disappearance of the 90,000 MW determinant in association with chymase-mediated priming for degranulation and the inability of chymase to mediate degranulation of trypsin-treated RSMC, which lack this membrane protein, suggests that it is involved in chymase-mediated RSMC degranulation.

Animals↗
PubMed1986

[Foreign bodies of unknown origin found in a serosal hematoma between the stomach and the pancreas of a patient].

An autopsy of a 55-year-old man who had died suddenly revealed extensive intra-abdominal bleeding and a serosal hematoma between the stomach and the pancreas, in which numerous foreign bodies were found. They were located just adjacent to pancreatic tissue which had undergone changes of acute necrotizing pancreatitis. It was assumed that they had been shaped by a pathological mechanism contributing much to the sudden death of the patient. The nature of the foreign bodies was investigated by comparing their microscopic sections with those of various living organisms and by testing their chemical character with some histochemical methods. However, they had no similarities to known foreign bodies of animal or plant origin found in pathological sections of human tissues and no conclusive evidence on their chemical nature could be obtained either. Our unified opinion is that the foreign bodies might have been formed in human tissues in situ as a result of the pathological tissue changes. The morphological features of the bodies are described in detail and their significance is discussed.

Acute Disease↗
PubMed1987

Biochemical characterization of a mast cell plasma membrane antigen shared by mouse serosal, culture-derived, and virally transformed mast cells.

The expression of the antigenic determinant identified by the B54.2 rat monoclonal antibody on four populations of mouse mast cells has been quantified, and the epitope-bearing surface antigen and its biosynthesis have been characterized. As assessed by indirect immunofluorescence staining and flow cytometric analysis, B54.2 antibody bound to serosal mast cells (S-MC), bone marrow culture-derived mast cells (BM-MC), fetal liver culture-derived mast cells (FTL-MC), and Abelson murine leukemia virus-transformed FTL-MC (ABFTL-MC). However, the intensity of cell surface fluorescence exhibited by ABFTL-MC was approximately eightfold less per cell compared with nontransformed, culture-derived mast cells. Immunoprecipitation of B54.2 antibody-binding molecules from each population of mast cells labeled intrinsically with [35S]methionine and analysis by SDS-PAGE demonstrated that the B54.2 epitope was expressed in each case on two noncovalently associated proteins of 110,000 Mr and approximately 130,000 Mr, but that the percentage of radiolabel in the latter species was approximately threefold less in ABFTL-MC than in BM-MC. As assessed by pulse-chase analysis with [35S]methionine, the 110,000 Mr protein was a precursor of the 130,000 Mr molecule ("B54.2 antigen") synthesized by BM-MC. Labeling of BM-MC with [35S]methionine in the presence of tunicamycin followed by immunoprecipitation and SDS-PAGE of B54.2 antibody-binding material revealed a single species of 93,000 Mr, indicating that the native molecules contained N-linked carbohydrate. Endoglycosidase H treatment of the glycoproteins precipitated by B54.2 antibody from BM-MC reduced the Mr of the 110,000-Mr molecule to 93,000 Mr without an appreciable change in the 130,000-Mr species. These data indicate that the 110,000-Mr precursor form is a "high mannose" type glycoprotein and the 130,000-Mr membrane surface B54.2 antigen is a "complex" type glycoprotein, and that the epitope recognized by the B54.2 antibody on the surface of the mouse mast cell populations is located on the 93,000-Mr peptide core.

Animals↗
PubMed1989

Activation- and phorbol ester-stimulated phosphorylation of a plasma membrane glycoprotein antigen expressed on mouse IL-3-dependent mast cells and serosal mast cells.

As assessed by immunoprecipitation analyses, expression of the epitope recognized by the rat mAb B23.1 is approximately sevenfold greater on the surface of mouse IL-3-dependent bone marrow culture-derived mast cells (BMMC) than on serosal mast cells (SMC) obtained directly from the peritoneal cavity. Immunoprecipitation of B23.1 antibody-binding molecules from Na[125I] surface-labeled BMMC and SMC followed by sizing on SDS-polyacrylamide gels under reducing conditions demonstrated that the epitope is located on molecules of 49,000 and 47,500 Mr, respectively. An additional immunoprecipitated molecule of 42,000 Mr was detected from BMMC intrinsically radiolabeled with [35S]methionine, and pulse-chase analyses revealed that this species was a biosynthetic precursor of the 49,000 Mr cell surface form of the Ag. Treatment of the immunoprecipitated 42,000 and 49,000 Mr forms with endoglycosidase F reduced the Mr of both to 37,000, as did intrinsic radiolabeling of BMMC in the presence of tunicamycin, indicating that both the 42,000 Mr precursor form and the 49,000 Mr cell surface molecule (gp49) contained N-linked carbohydrate. Activation of [32P]orthophosphate-labeled BMMC by sensitization with mouse monoclonal IgE anti-TNP and challenge with TNP-BSA or by exposure to the calcium ionophore A23187 elicited the rapid phosphorylation of gp49 but not of its precursor forms, as did treatment of the cells with PMA. Elution of phosphorylated and immunoprecipitated gp49 from SDS-polyacrylamide gels followed by partial acid hydrolysis of the protein and phosphoamino acid analysis by high voltage thin-layer electrophoresis on cellulose plates indicated that serine, but not threonine or tyrosine, was phosphorylated upon stimulation of BMMC with IgE/Ag, calcium ionophore, or PMA. Cholera toxin did not elicit phosphorylation of gp49. These data suggest that gp49, a plasma membrane glycoprotein preferentially expressed by mouse BMMC, may be either directly or indirectly phosphorylated via protein kinase C during mast cell activation-secretion.

Animals↗
PubMed1989

Modulation of chymase-mediated rat serosal mast cell degranulation by trypsin or diisopropyl fluorophosphate.

Exposure of rat serosal mast cells (RSMC) to chymase, an endogenous secretory granule serine protease, at 37 degrees results in exocytosis, as determined by beta-hexosaminidase release. As the number of RSMC is increased with a set amount of chymase, the net percentage beta-hexosaminidase release decreases linearly, implying a finite set of cellular interactions per chymase unit. Pretreatment of RSMC with trypsin at 37 degrees renders them refractory to subsequent exocytosis mediated by chymase in a dose- and time-dependent fashion, with complete refractiveness occurring by 15 min at 37 degrees with 2.5 micrograms trypsin/ml. Anti-IgE-mediated coupled activation-secretion of RSMC is not affected by the same trypsin pretreatment. When RSMC are pretreated with trypsin (2.5 micrograms/ml) for 0-120 min at 1 degree a progressive loss of sensitivity to activation by chymase at 37 degrees occurs. RSMC susceptibility to chymase-mediated degranulation after trypsin pretreatment can be partially regenerated by culturing the RSMC for about 24 hr in medium at 37 degrees. These findings suggest that a trypsin-sensitive constituent, possibly a receptor or substrate, is necessary for the functional interaction of chymase with RSMC. When added with diisopropyl fluorophosphate (DFP), chymase does not induce RSMC degranulation at 37 degrees. However, if the DFP is removed before addition of chymase at 37 degrees or is added after the chymase-priming event occurs at 1 degree, subsequent degranulation at 37 degrees is not inhibited. Thus, the induction and not the secretion phase is DFP-inhibitable in chymase-induced activation-secretion. In addition, the priming but not the exocytosis phase of chymase-initiated RSMC activation-secretion, which is not dependent on temperature and calcium ion concentration, involves a cellular trypsin-sensitive protein.

Animals↗
PubMed1989

[Prognostic factors in gastric cancer with serosal invasion--importance of the extent of cancer infiltration in the subserosal layer].

The extent of cancer infiltration in the subserosal layer has been examined in 214 stomachs resected for cancer with a serosal invasion. The extent was 4 cm or less in 109 patients (Group A) and 5 cm or more in 105 patients (Group B). The resection was estimated as being non-curative in 26% of Group A and in 52% of Group B (p less than 0.001). Peritoneal dissemination was the outstanding non-curative factor in the latter. The five-year survival rate was 39% in Group A and 14% in Group B (p less than 0.001). The survival rate after the curative resection was 49% and 26%, respectively (p less than 0.01). In Group B, peritoneal dissemination was the main mode of recurrence after the curative resection.

Adult↗
PubMed1989

Modified vertical banded gastroplasty. Technique with vertical division and serosal patch.

A modification of Mason's vertical banded gastroplasty for morbid obesity is presented, along with experience from 62 treated patients. The modification consists of vertical separation of the reservoir and gastric cavities by division of the gastric wall with a linear cutter and use of a serosal patch to prevent leakage to the abdomen. No breakdown of the vertical suture line occurred. The one major complication was a posterior esophageal injury. Subcutaneous wound infection occurred in two patients. There was no pulmonary embolism and no death. The average weight loss at 1 year postoperatively was 40 kg from the initial body weight, or 61.5% of the excess weight. The body mass index at 1 year had fallen from 47 to 32.45.

Adolescent↗
PubMed1986

Rat serosal mast cell degranulation mediated by chymase, an endogenous secretory granule protease: active site-dependent initiation at 1 degree C.

Exposure at 37 degrees C of rat serosal mast cells (RSMC) to chymase, an endogenous secretory granule serine protease, results in exocytosis as determined by the release of another secretory granule enzyme, beta-hexosaminidase. Chymase-mediated RSMC degranulation does not occur at 1 degree C; however, exposure of RSMC to chymase at 1 degree C followed by the removal of buffer and the resuspension of the cells in buffer alone at 37 degrees C results in exocytosis equivalent to that obtained by direct exposure of RSMC to chymase at 37 degrees C. Maximal chymase-mediated RSMC degranulation at 37 degrees C is Ca2+-dependent and Mg2+-independent. The dose-dependent degranulation-inducing interaction of chymase and alpha-chymotrypsin with RSMC at 1 degree C is Ca2+-independent, whereas subsequent exocytosis at 37 degrees C in new buffer without added enzyme still requires Ca2+. Specific binding of 125I-labeled alpha-chymotrypsin to RSMC does not occur at 1 degree C, implying that the inducing action of chymase is not a simple ligand-receptor binding. The enzyme inhibitors diisopropyl fluorophosphate and lima bean trypsin inhibitor inhibit subsequent exocytosis at 37 degrees C only if they are added within the first 10 min of the interaction of RSMC and chymase at 1 degree C, implying that an active site-dependent inducing event occurs between RSMC and chymase at 1 degree C. Thus, chymase-induced coupled activation-secretion can be divided into a cation- and temperature-independent initiation phase, which is dependent on the active site of exogenously added chymase and a subsequent temperature-dependent and calcium-augmented cellular secretion phase.

Animals↗
PubMed1988

[Surgical problems encountered in cases of S0 (serosal invasion-free) gastric cancers].

In this paper we have studied 649 resected cases of S0 (macroscopically negative serosal invasion) gastric cancer, this number of S0 gastric cancer resections experienced from a total number of 1692 patients treated at our hospital during the previous 16 years. The five-year survival rate of S0 cancers was 94% for patients given curative resections. Most of S0 cancers were histologically restricted within the pm layer but a few had reached the ss gamma or se layer. Non-curative factors in S0 cancers we recomposed of cancer positive stumps in the IIb-like margin, liver metastasis in the differentiated type carcinomas with ss invasion, and surgically left lymph node metastasis in the advanced carcinomas. As for lymph node dissections, our study reveals that an R2 dissection in the C and M regions, and a R3 or R2 + No.12 dissection for the A region are recommended. Modes of recurrence were characterized by liver or other hematogeneous metastasis in pm cancers or lymph node-positive cancers at the antrum, and by a peritoneal recurrence at the corpus in cases of advanced cancers. Histological ps(-) cancers showed a different survival result than did the S0 cancers and S(+) cancers.

Aged↗
PubMed1987

[Diagnosis of degree of serosal invasion of carcinoma of the colon by angiography].

Angiography (AG) using Prostaglandin E1 was performed on 35 cases of carcinoma of the colon in order to diagnose the degree of serosal invasion. The findings of AG were classified into 4 groups: AG-S3, abnormal change (like irregularity and/or encasement) up to marginal vessels; AG-S2, abnormality up to vasa recta; AG-S1, abnormality of penetrating branches of vasa recta; AG-S0, no distinct findings of above mentioned vessels. 1) Diagnosis of AG is in accord with the visible postoperative findings in 82.9%. 2) Diagnosis of AG is in accord with the histopathological findings in 32.4%. 3) Postoperative examinations confirmed the AG diagnosis precisely but the conflict with histopathological findings should not be overlooked. This may be the results of inflammatory change, adhesion and fibrosis around the carcinoma of the colon.

Adenocarcinoma↗
PubMed1985

Identification of the neutral glycosphingolipids of murine mast cells: expression of Forssman glycolipid by the serosal but not the bone marrow-derived subclass.

The expression of neutral glycosphingolipids by mouse T cell-dependent, bone marrow-derived mast cells (BMMC) obtained in vitro was determined by chromatographic and immunochemical criteria. Neutral glycosphingolipids were isolated from BMMC by extraction of 3 to 5 X 10(8) cells in chloroform/methanol (1/1, v/v) and chromatography on DEAE-Sephadex, and were analyzed by thin layer chromatography with orcinol staining. The predominant neutral glycosphingolipids of BMMC were glucosylceramide (CMH), lactosylceramide (CDH), globotriosylceramide (CTH), globotetraosylceramide (globoside), and a molecule migrating slightly faster than gangliotetraosylceramide (asialo GM1) and slower than globopentaosylceramide (Forssman glycolipid). The profiles on thin layer chromatograms of the neutral glycosphingolipids were the same for BMMC derived from BALB/c, C57BL/6, WBBF1-W/Wv, and WBBF1-+/+ mice, and for cells differentiated in either WEHI-3 conditioned medium or concanavalin A-splenocyte conditioned medium. High performance liquid chromatography of benzoylated neutral glycosphingolipids of BMMC on a Zipax column confirmed the identity of the four neutral glycosphingolipids identified by thin layer chromatography. The fifth major glycosphingolipid had an elution time greater than that of globotetraosylceramide and did not co-elute with any of the standards tested. Direct biochemical analyses of the neutral glycosphingolipids of mouse serosal mast cells (SMC) were not feasible because only 2 X 10(6) SMC could be isolated per 100 mice. However, mouse SMC bound a rat monoclonal anti-globopentaosylceramide antibody (M1/87.27.7) and rat monoclonal B1.1 antibody, as assessed by indirect immunofluorescence and flow cytometry, whereas mouse BMMC did not. The binding of B1.1 antibody to SMC could be blocked by the anti-globopentaosylceramide antibody, and the specificity of B1.1 antibody for globopentaosylceramide was confirmed immunochemically with the use of a solid phase radioimmunoassay. As estimated immunochemically, the amount of globopentaosylceramide in mouse SMC was 62 ng/10(6) cells, whereas BMMC contained less than 8 ng/10(6) cells. Thus, the expression of globopentaosylceramide is a characteristic of the mouse SMC that is lacking in the T cell-dependent BMMC.

Animals↗
PubMed1985

Pharmacological modulation of activation-secretion of rat serosal mast cells by chymase, an endogenous secretory granule protease.

The action of pharmacologic agents on chymase-induced exocytosis of beta-hexosaminidase and arachidonic acid (AA) metabolism by rat serosal mast cells (RSMC) was determined and compared with their effects on anti-IgE induced activation. Indomethacin (INDO) (less than or equal to 10 microM), a cyclooxygenase inhibitor, did not affect chymase- or anti-IgE-mediated exocytosis, while completely inhibiting prostaglandin D2 (PGD2) release at 1.25 microM. Theophylline (THEO), mepacrine, 3-amino-1-[m-(trifluoromethyl)-phenyl]-2-pyrazoline (BW755C), and diethylcarbamazine (DEC), inhibitors of adenosine binding and phosphodiesterases, phospholipases, AA metabolism, and vesicular transport as well as leukotriene A4 formation, respectively, inhibited exocytosis with ID50 values of 3.4, 0.22, 3.4 and 1.9 mM for chymase and 2.4, 0.17, 2.8 and 5.2 mM for anti-IgE. These agents inhibited net PGD2 release with ID50 values of 2.1, 0.04, less than 0.05, and 1.5 mM for chymase and of 0.5, 0.1, less than 0.05, and 4 mM for anti-IgE. 5,6-Dehydroarachidonic acid (DHA) and arachidonyl hydroxylamine (AH), 5-lipoxygenase inhibitors, did not affect chymase-mediated exocytosis; anti-IgE-mediated exocytosis was not altered by AH but was suppressed by DHA (ID50 = 20 microM). Nordihydroguaiaretic acid (NDGA), an antioxidant, inhibited chymase-mediated exocytosis dose-dependently (ID50 less than or equal to 13.3 microM) while decreasing anti-IgE-mediated exocytosis by only 30% at 2.5-20 microM; net PGD2 release induced by both stimuli was inhibited dose-dependently. 2',5'-Dideoxyadenosine (DDA) and 1,6-di(0-(carbamoyl)cyclohexanone oxime)hexane (RHC 80267) and inhibitors of adenylate cyclase and of di-triglyceride lipases, respectively, had little effect on exocytosis induced by chymase but inhibited that induced by anti-IgE with ID50 values of 0.4 mM and 37 microM, respectively. With DDA the inhibition of net PGD2 release occurred with anti-IgE but not chymase, whereas RHC 80267 inhibited both chymase and anti-IgE-mediated PGD2 release. Differential inhibition of activation-secretion suggests either that chymase provides a step inhibited in IgE-mediated exocytosis by DDA, RHC 80267 and DHA, or that the activating pathway initiated by chymase is distinct.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1985

Demonstration of action of muzolimine on the serosal side of Henle's loop cells.

Muzolimine, a new diuretic, is known to act by inhibiting Na transport along the ascending limb of Henle's loop. Because of its ineffectiveness when perfused into the lumen, and as a result of experiments on frog skin, it is believed that muzolimine acts from the serosal cell side, unlike all other diuretics. We decided to assess the site of action of muzolimine (mucosa versus serosa) by experiments on rats. The animals were anesthetized, both ureters cannulated, and a hydronephrosis established in the left kidney by applying a counterpressure to the ureter, slowly and progressively increased up to 60 cm H2O in 3 minutes and kept stable for 20 minutes. Then either muzolimine 1.2 mg, or furosemide 4 mg, was injected i.v. together with 131I-Hypaque as a glomerular marker. Three minutes later the hydronephrosis was released in the left kidney by cutting the catheter, and urine collections were started simultaneously in both kidneys into 25 microliter glass capillaries, that were filled in continuous sequence and numbered progressively. In each urine sample from each glass capillary Na and 131I-Hypaque were measured. In 5 animals receiving furosemide, UNa rose in the left post-obstructed kidney and reached a plateau level by the 3rd to 5th sample. The rise in Na concentration, indicating delivery of urine whose Na reabsorption had been inhibited along the loop of Henle paralleled that in 131I-Hypaque, indicating that the diuretic and the glomerular marker had reached Henle's loop simultaneously, following filtration after the hydronephrosis had been discontinued.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗