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Modes of Cl- transport across the mucosal and serosal membranes of urodele intestinal cells.

The characteristics of Cl- movement across luminal and basolateral membranes of Amphiuma intestinal absorptive cells were studied using Cl(-)-sensitive microelectrodes and tracer 36Cl techniques. Intracellular Cl- activity (aiCl) was unchanged when serosal Cl- was replaced; when luminal Cl- was replaced cell Cl- was rapidly lost. Accordingly, the steady state aiCl could be varied by changing the luminal [Cl]. As luminal [Cl] was raised from 1 to 86 mM, aiCl rose in a linear manner, the mucosal membrane hyperpolarized, and the transepithelial voltage became serosa negative. In contrast, the rate of Cl- transport from the cell into the serosal medium, measured as the SITS-inhibitable portion of the Cl- absorptive flux, attained a maximum when aiCl reached an apparent value of 17 mM, indicating the presence of a saturable, serosal transport step. The stilbene-insensitive absorptive flux was linear with luminal [Cl], suggestive of a paracellular route of movement. Intracellular aCl was near electrochemical equilibrium at all but the lowest values of luminal [Cl] after interference produced by other anions was taken into account. aiCl was unaffected by Na replacement, removal of medium K, or elevation of medium HCO-3. Mucosae labeled with 36Cl lost isotope into both luminal and serosal media at the same rate and from compartments of equal capacity. Lowering luminal [Cl] or addition of theophylline enhanced luminal Cl- efflux. It is concluded that a conductive Cl leak pathway is present in the luminal membrane. Serosal transfer is by a saturable, stilbene-inhibitable pathway. Luminal Cl- entry appears to be passive, but an electrogenic uptake cannot be discounted.

Animals↗

Intestinal HCO3- secretion in Amphiuma: stimulation by mucosal Cl- and serosal Na+.

The requirement for Na+ and Cl- in the bathing media to obtain a maximal HCO3- secretory flux (JHCO3-) across isolated short-circuited Amphiuma duodenum was investigated using titration techniques and ion substitution. Upon substitution of media Na+ with choline, HCO3- secretion was markedly reduced. Replacement of media Cl- produced a smaller reduction of JHCO3-. The presence of Cl- enhanced HCO3- secretion only if Na+ was also in the media. Elevation of media Na+ or Cl- in the presence of the other ion produced a saturable increase of JHCO3-. In the presence of Na+, Cl- stimulated JHCO3- when added to the mucosal but not the serosal medium. In the presence of Cl-, Na+ elevated JHCO3- when added to the serosal but not the mucosal medium. The ability of mucosal Cl- to stimulate JHCO3- was not apparently dependent on mucosal Na+. Simultaneous addition of 10 mM Cl- to the Na+ -free mucosal medium and 10 mM Na+ to the Cl- -free serosal medium stimulated JHCO3- above levels produced by serosal Na+ alone. In conclusion, intestinal HCO3- secretion required mucosal Cl- and serosal Na+ and did not involve mucosal NaCl cotransport. The results are consistent with a mucosal Cl- absorptive mechanism in series with parallel basolateral Na+ -H+ and Cl- -HCO3- exchange mechanisms.

Animals↗

Covering of the terminal ureter with de-serosalized muscle layer of the ileum for antireflux ureteroileostomy: an experimental study in dogs and a preliminary clinical trial.

We demonstrated a new operative technique for antireflux ureteroileostomy in dogs. The severed ureter was reimplanted into the isolated ileum. Ten terminal ureters were covered with a 2 x 2 cm2 section of de-serosalized ileal wall after direct ureteroileostomy, and another six terminal ureters were covered with a 2 x 2 cm2 section of non-de-serosalized full-thickness ileal wall. Thirteen ureters were directly anastomosed to the ileum without any additional procedures. The bladder was augmented by the detubularized ileum with the ureter. Postoperative evaluations on ureteral stenosis and reflux were performed monthly for 3 months. The ureters covered with the de-serosalized ileal wall prevented ureteral reflux even when the intravesical pressure climbed as high as 100 cm H2O. Although two of these ten ureters demonstrated strictures at the precise site of direct ureteroileostomy, the sections of the ureters covered with the de-serosalized ileal wall were opened and did not collapse. In the resected specimens, the terminal ureters were found in the intramural part of the ileum. The ureters covered with the full-thickness of ileal wall did not prevent reflux. Our method of covering the terminal ureter with the de-serosalized ileal wall worked well as an antireflux mechanism, and the intramural ureter did not cause ureteral stricture. After this animal experiment, we introduced this antireflux mechanism clinically.

Aged↗

Gap junction modulation in rat uterus. I. Effects of estrogens on myometrial and serosal cells.

The ability of estradiol benzoate (E2 B) and diethylstilbestrol (DES) to affect the formation and internalization of gap junctions was examined in several uterine cell types from hypophysectomized rats. Both myometrial and serosal cells respond to daily administration of E2 B or DES by increasing gap junction membrane in a dose-dependent fashion. The myometrial cell response arises from a zero base with gap junctions detected within 24 h of a single injection of 500 micrograms E2 B, while five daily injections of 5 micrograms E2 B were required to induce their formation at the lower dosage. Uterine serosal cells exhibit small macular gap junctions 60 days posthypophysectomy with E2 B stimulation leading to an increase in the number of macular gap junctions and the induction of annular gap junctions. Myometrial cell gap junctions were modulated by L-thyroxine and progesterone when administered in combination with E2 B but were without effect when administered alone. Combination of indomethacin with E2 B injections antagonized E2 B-stimulated junction growth in both myometrial and serosal cells, however, only serosal cells responded to exogenous prostaglandin (PG) injections, with PGE1 increasing and PGF2 alpha decreasing the number of serosal cell gap junctions. These studies support the assumption that the induction of gap junctions in uterine myometrium is hormone dependent.

Animals↗

Transepithelial sodium transport and carbon dioxide production by the toad urinary bladder in the absence of serosal sodium.

1. The production of CO2 in relation to sodium transport by toad urinary bladder has been examined in the absence of sodium from the serosal medium. 2. Replacement of serosal sodium by choline increased CO2 production without stimulating short-circuit current. Replacement of serosal medium by Tris did not have this effect. 3. With serosal sodium Ringer replaced by Tris Ringer, the ratio of sodium transported to CO2 produced was not altered significantly. 4. The results therefore suggest that there is no important recycling of sodium between the serosal medium and the transporting epithelial cells.

Animals↗

Effects of serosal hypertonicity on water permeability in toad urinary bladder.

We studied in toad urinary bladder the effects of serosal hypertonicity on tissue water permeability, granular cell luminal membrane water permeability, and granular cell luminal membrane particle aggregates and compared them with effects of antidiuretic hormone (ADH). In tissues challenged by a hypertonic (447 mosmol/kgH2O) serosal bath, luminal membrane aggregates were structurally similar to those caused by ADH. The tissue water permeability increase induced by serosal hypertonicity was much less than that caused by a maximally stimulating concentration of ADH on tissue in isotonic serosal baths with approximately the same transmural gradient. The difference is explained not only by a reduced incidence of luminal membrane aggregates but also by an increased resistance to water movement at a postluminal membrane site. Measurements of luminal membrane water permeability showed a close correlation with luminal membrane aggregate frequency, indicating that the calculated permeability of an individual aggregate was a constant. Thus the relation of luminal membrane aggregates to tissue osmotic permeability is modified by serosal hypertonicity. Morphological examination of these tissues suggested that luminal membrane aggregates may be less stable in the absence of hormone. This was evident by the proportionally greater number of structures interpreted as aggregates captured in the process of disassembly ("patches"). Membrane depressions containing intramembrane particles ("craters") were also observed. They corresponded in terms of frequency and size to coated pits as seen in thin sections.

Animals↗

PAH transport in rock crab urinary bladder. II. Luminal and serosal steps.

To characterize the organic anion transport properties of the luminal (1) and serosal (s) membranes of crab urinary bladder, initial (10 min) fluxes (J) and tissue accumulations (Ac) of 10 microM PAH were measured in the absence and presence of 1 mM BCG (nontransported, high-affinity competitor). Control bladders exhibited net reabsorptive transport with a mean Jl leads to s/Js leads to 1 of about 7; concentrative transport of p-aminohippuric acid (PAH) occurred only across the luminal cell (c) membrane. With luminal PAH, luminal bromocresol green (BCG) reduced Jl leads to c, Jc leads to s, and Ac by about 85%; serosal BCG reduced Jc leads to s, increased Ac but had no effect on Jl leads to c. With serosal PAH, serosal BCG reduced Js leads to c, Jc leads to l, and Ac; luminal BCG had no effects on either fluxes or tissue accumulation. When bladder sheets were loaded with radiolabeled PAH, mounted in a chamber, and exposed to flowing crab Ringer solution on both sides, Jc leads to s was nearly twice as large as Jc leads to l; BCG significantly reduced Jc leads to s but not Jc leads to l. With unlabeled PAH in the efflux media, Jc leads to s was increased. The data are consistent with a model featuring an inwardly directed pump at the luminal membrane, a facilitated carrier at the serosal membrane, and nonmediated pathways at both membranes.

Aminohippuric Acids↗

Serosal tissue: reactive tissue as a model for understanding mesotheliomas.

Serosal tissues consist of a surface mesothelial layer and subsurface spindled connective tissue cells. Surface cells are decorated with antibodies to both low and high molecular weight cytokeratin whereas subserosal cells only express the intermediate filament vimentin. Serosal injury results in the proliferation of multipotential subserosal cells (MSC) which have the ultrastructural morphology of myofibroblasts and yet co-express low molecular weight cytokeratin and vimentin. These cells appear responsible for the re-establishment of surface mesothelium during which they acquire high molecular weight cytokeratin and loose vimentin. There are many parallels between reactive and neoplastic serosal tissues. Desmoplastic/sarcomatoid mesotheliomas resemble the MSC and co-express low molecular weight cytokeratin and vimentin and epithelial mesotheliomas resemble surface mesothelium and express both low and high molecular weight cytokeratin. The ability of normal serosal tissue to modulate its cell shape and intermediate filament expression helps understand the diversity of serosal tumors.

Antibodies↗

Dose-dependent stimulatory and inhibitory effects of luminal and serosal n-butyric acid on epithelial cell proliferation of pig distal colonic mucosa.

Large bowel bacteria convert various carbohydrates into short-chain fatty acids (SCFA). SCFA stimulate epithelial cell proliferation of the large intestine in vivo and inhibit that of various cells in vitro. Supposing that too high concentration of SCFA on the serosal side is responsible for their inhibitory effect in vitro, we studied effects of luminal and serosal n-butyric acid (0, 0.1, 1, or 10 mmol/L, adjusted to neutral pH) on the epithelial cell proliferation rate of pig colonic mucosa in organ culture taking crypt cell production rate (CCPR) as the measure of proliferative activity. With 0 or 0.1 mmol/L n-butyric acid on the serosal side, luminal n-butyric acid increased CCPR at 1.0 mmol/L, and decreased CCPR at 10 mmol/L when compared to the luminal 0 mmol/L control. With 1.0 or 10 mmol/L serosal n-butyric acid, luminal n-butyric acid depressed CCPR dose-dependently. The above results indicated that n-butyric acid stimulated colonic epithelial cell proliferation at low concentration and inhibit it at high concentration with interaction effect to enhance the inhibitory action. The stimulatory effect of a low dose of serosal n-butyric acid may be responsible for the distant trophic effect of SCFA.

Animals↗

[Correlations between invasion of gastric cancer to serosal layer and other relevant factors].

OBJECTIVE: To study correlations between invasion of stomach cancer to serosal layer and such factors as size and type of tumor, depth of ulcer, gastric wall contraction, etc. METHODS: Gastric cancer specimens from 150 patients admitted to the hospital in March 1993 through March 1997 were examined. RESULTS: The frequency of tumor invasion to the serosa in gastric cancer of Borrmann type I, II, III and IV was 8.3%, 23.4%, 32.9% and 76.2%, respectively. The frequency of serosal involvement was 13.6% in tumors with a diameter < or = 3.0 cm which was significantly less frequent than in tumors with a diameter > 3.0 cm. The frequency of serosal involvement increased with the increase in depth of ulcer and with spastic contraction of gastric wall as observed in pre-operative barium meal examination. That of serosal involvement varied with degree of differentiation of the tumor, being much lower in well- and moderately well-differentiated adenocarcinomas (10.3%) than in poorly differentiated ones (62.8%). The serosa was frequently invaded by mucinous adenocarcinoma (42.9) and signet cell carcinoma (83.3%). CONCLUSION: Invasion of gastric cancer to serosal layer correlates, to various extents, with the tumor size and type, status of cell differentiation, and depth of ulcer.

Adenocarcinoma↗

Neoadjuvant chemotherapy with CDDP and 5-fluorouracil for gastric cancer with serosal invasion.

Many gastric cancer patients who recur peritoneally are initially diagnosed with serosal invasion. To clarify the usefulness of neoadjuvant chemotherapy with 5-fluorouracil (5-FU) +/- cisplatin (CDDP), neoadjuvant versus no preoperative chemotherapy for gastric cancer with preoperative serosal invasion was investigated. The patients were treated preoperatively with 5-FU 300 mg/m(2)/day for 2 weeks (F group; n=40), 5-FU 300 mg/m(2)/day for 2 weeks + CDDP 15 mg/m(2)/day for 2 days (FP group; n=80) or nothing (C group; n=100). A total of 78% of patients in C, 65.0% in F and 67.5% in FP group were classified as T3 or higher surgically. In patients without peritoneal metastasis, the positive peritoneal lavage cytology was 29.2% in C, 11.8% in F, and 12.2% in FP patients (p=0.0279). Serosal invasion was found histologically in 60.0% of C, 30.0% of F, and 33.8% of FP patients (p=0.001). There were no serious drug reactions and no increases in morbidity or mortality using either regimen. The 5-year survival rate was 47.0% in F and 50.9% in FP patients, but only 33.2% in C patients (p=0.0042). In conclusion, neoadjuvant chemotherapy with 5-FU +/- CDDP for gastric cancer patients with serosal invasion may reduce positive peritoneal cytology, eliminate cancer cells from the serosal surface, and improve prognosis.

Aged↗

Serosal invasion as the single prognostic indicator in stage IIIA (T3N1M0) gastric cancer.

Prognostic factors of gastric cancer with positive serosal invasion and regional lymph node metastasis were evaluated by multivariate analysis. Sixty-seven patients with the T3N1M0 subgroup of stage IIIA disease were evaluated, in which 34.9 +/- 13.4 nodes were dissected in extended lymph node dissection, and 6.5 +/- 6.2 were metastatic. Routine postoperative systemic chemotherapy with mitomycin C and N1-(2'-tetrahydrofuryl)-5-fluorouracil was administered. With this approach, the 5-year survival rate of stage IIIA disease was 47.6%. By Cox proportional hazards model, diameter of serosal invasion was the only significant determinant of prognosis in the T3N1M0 subgroup. The predicted 5-year survival rate for 24 patients with serosal invasion less than 3.0 cm in diameter was 59.5%, compared with 11.5% for 38 patients with invasion of 3.0 cm or larger in diameter. The number of metastatic nodes and the type of operation (total gastrectomy or less than total gastrectomy) did not affect the prognosis. When gastric cancer has both positive serosal invasion and metastatic regional lymph nodes, the diameter of serosal invasion is the more important factor for predicting prognosis.

Adenocarcinoma↗

[A study of DNA heterogeneity on gastric cancer with serosal invasive exposure].

In order to assess clinical significance, the DNA content in gastric cancer with serosal invasive exposure from 50 patients was determined by flow cytometry. The DNA histograms could be measured in two different vertical portions, on the mucosal and serosal sides. DNA heterogeneity was found in 15 patients (30.0%). These cases were divided into 4 groups according to the combination of DNA ploidy patterns. There were no significant differences in clinicopathological characteristics or survival rate between these 4 subgroups. Furthermore, the serosal invasion index (SII) defined as the ratio of serosal extent to mucosal extent was examined to determine the malignancy potential. All cases were divided into 2 groups, high SII and low SII, according to the value of SII. The survival rate was significantly lower in the high SII-aneuploid group compared with the low SII-diploid group. These results suggested that DNA analysis, subclassified by the serosal invasion index, is useful for assessment of the patient's prognosis.

DNA, Neoplasm↗

Asymmetrical oxygen availability from serosal and luminal sides of rat distal colon epithelium.

Short-circuit current (Isc) and transepithelial potential difference (PD) of the rat distal colon mucosa are sensitive to acute hypoxia in vitro. The relative contribution of luminal and serosal oxygenation in sustaining Isc and PD was assessed. Rat distal colon Isc and PD responses to hypoxia and reoxygenation of preparations of mucosa-submucosa, and of isolated mucosa (with and without the mucus gel layer), mounted in an Ussing chamber, and of sacs of everted and non-everted isolated mucosa, were measured. In Ussing chambers, a 5-min total (bilateral) hypoxia reduces Isc and PD by 50 to 70%, while an overshoot was observed on reoxygenation. Serosal hypoxia caused about the same effect as total hypoxia, with complete recovery on reoxygenation. Luminal hypoxia had no effect in either Isc or PD. After total hypoxia, selective serosal reoxygenation allowed complete recovery of Isc and PD; addition of luminal reoxygenation did not further increase Isc and PD. Luminal reoxygenation after total hypoxia did not modify the decrease in Isc and PD, but addition of serosal reoxygenation led to complete recovery. A similar behaviour was seen in isolated mucosa preparations without the mucus gel layer. Baseline Isc and PD of everted sacs were about 45% of those of non-everted sacs, but their response to a hypoxic challenge was slightly attenuated. On reoxygenation, both everted and non-everted sacs showed complete recovery. Summing up: serosal oxygenation is both necessary and sufficient to sustain rat distal colon Isc and PD, while luminal oxygenation is not; there seems to exist a barrier, different from the mucus gel layer, for oxygen access from the luminal side of the epithelium; and distal colon isolated mucosa everted sac preparations are suboptimally oxygenated.

Animals↗

Serosal cytologic study to determine free mesothelial penetration of intraperitoneal colon cancer.

BACKGROUND: The presence of complete transmural penetration with tumor cells at the free mesothelial surface in patients with intraperitoneal colon cancer is an important prognostic feature and may alter the decision regarding adjuvant chemotherapy. METHODS: In this prospective study of 65 patients, specimens obtained by scraping the serosa overlying the primary tumor mass were analyzed by routine Papanicolaou cytologic study. RESULTS: Malignant cells were present in 23.1% of patients. In 46 patients with histologic pT3 tumors (through the muscularis propria but not through serosa), serosal cytologic study results were positive in 26.1% of patients. Serosal cytologic results were positive from an area of normal colon at least 10 cm proximal or distal to the primary tumor in one patient. CONCLUSIONS: Serosal cytologic study appeared to be a simple and reliable method to detect serosal penetration and the presence of tumor cells at the mesothelial surface.

Colonic Neoplasms↗

Serosal balls detected immunocytochemically in peritoneal lavage obtained during surgery.

Using the immunoperoxidase technique, we studied "serosal balls," which have features resembling those of cells from primary and metastatic tumors, and may thus complicate cytodiagnosis. Serosal balls were detected in 32 (18%) of 174 peritoneal washings. The balls consisted of oval clusters of cells in solid masses surrounded by flattened cells. The interior of the serosal balls was stained green with Papanicolaou method, showing the presence of homogeneous amorphous material, sometimes stained in a filamentous pattern. Almost all serosal balls were stained immunocytochemically for both keratin and vimentin. The interior was stained with antibodies against collagen types I and III. Therefore, these balls were fragments of serous membrane, and contained fibrous tissue and mesothelial cells.

Azure Stains↗

In vivo studies of mucosal-serosal transfer in rat jejunum.

In anesthetized rats, the appearance rates of a series of labeled substances in jejunal venous blood (phi B) and serosal bath (phi S) were measured in vivo (intestinal blood flow rate 1.5 ml min-1 g-1) after intraluminal administration of 0.5 ml buffer solution (initial concentration 1 mmol/1 or 1 GBq/1 tritiated water) into a closed jejunal segment (length 4-5 cm). Between 32% (erythritol) and 93% (salicylic acid) of the administered activity (unchanged substance and possible metabolites) appeared in the intestinal venous blood within 60 min. The fraction recovered from the serosal bath after 15 (60) min was 11 (6)% for tritiated water, 7 (4)% for aniline, 3 (7)% for aminopyrine, 5 (4)% for butanol, 3 (3)% for benzyl alcohol, 2 (4)% for benzylamine, 1-2% for benzoic acid, theophylline, methyl-alpha-D -glucopyranoside, L-lysine, antipyrine, and urea, and less than 1% for L-phenylalanine, D-galactose, erythritol, and salicylic acid. During single pass perfusion of a jejunal segment (length 3-4 cm) the fraction of serosal transfer phi S/(phi B + phi S) was 19% for tritiated water, 4.9% for antipyrine, 0.5% for benzoic acid, and 0.08% for salicylic acid. Distension of the intestinal wall by administration of 1 ml buffer solution instead of 0.5 ml increased the appearance rate of benzoic acid and antipyrine in intestinal venous blood by a factor of 2 and serosal transfer by a factor of approximately 3.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Localized fibrous tumour of serosal surfaces. Immunohistochemical and ultrastructural evidence for a type of mesothelioma.

It is uncertain whether localized lesions of serosal membranes have a kinship to mesotheliomas or are truly fibromatous in nature. Ultrastructural and immunohistochemical investigations were carried out on 12 localized benign and malignant pleural and peritoneal tumours from 10 patients. Electron microscopic findings, including the consistent and non-fibroblastic cellular organization of localized neoplasms, the presence of some form of intercellular junctions in 7 of 10 cases, basal lamina deposition in 3 cases, and polarized microvilli in one case indicated a form of mesothelial differentiation. Using monoclonal and polyclonal antibodies, positive immunostaining of tumour cells for cytokeratin peptides was detected in one case, while antibody to vimentin stained four cases. Light microscopic, ultrastructural and immunohistochemical features of one benign localized serosal tumour, with a unique blend of epithelial and spindle cells, provided further evidence for a histogenic link between localized serosal tumours and diffuse epithelial mesotheliomas. On the basis of the current findings and reports in the literature, it would appear that the majority of localized tumours of serosal membranes are a subset of mesothelioma, while a minority are fibromas.

Adult↗