Inhibitory actions of prostaglandin E1 on non-adrenergic non-cholinergic contraction in guinea-pig bronchi.

ZK110841 and AH6809, an agonist and an antagonist of prostaglandin DP-receptors on human platelets, were evaluated with a fibroblastic cell line from bovine embryonic trachea (EBTr) which specifically responds to prostaglandin D2 (PGD2). ZK110841, equipotent to PGD2, elevated the adenosine 3':5'-cyclic monophosphate (cyclic AMP) level in EBTr cells dose-dependently, being more than 100 fold over the basal level at 1 microM. The half-maximally effective concentration of PGD2 or ZK110841 was 10-30 nM. Increasing concentrations (10(-7)-10(-4) M) of AH6809 (which possesses negligible intrinsic agonist activity) produced parallel shifts to the right of dose-response curves to PGD2 and ZK110841. Schild plots of these data were linear (correlation close to unity) and pA2 values against PGD2 and ZK110841 were calculated to be 6.36 and 6.57, respectively, indicating that AH6809 is a simple and competitive antagonist. These results demonstrate that ZK110841, AH6809 and EBTr cells will be useful for characterization of DP-receptors.     

Immunoglobulin G from subacute sclerosing panencephalitis brain as an immunological reagent.

"Natural" hemagglutinin titers against a panel of fixed erythrocyte antigens were determined for groups of Minnesota miniature swine reared conventionally, in a specific pathogen-free facility, and in germfree isolators. Sera were assayed for hemagglutination (HA) titers by the microtiter method against 12 species of erythrocytes stabilized by treatment with pyruvic aldehyde and formaldehyde. These erythrocytes were stable for up to 2 years and gave slightly enhanced HA titers as compared to fresh, unfixed erythrocytes. Of the sera from conventional swine tested, the highest "natural" HA titers were directed towards rabbit, cat, swine dog, and burro erythrocytes (greater than 1:1,000), intermediate titers were detected against human A, B, and O, and sheep, pig, and chicken erythrocytes (1:64 to 1:1,000), whereas the lowest titers were found against ox and goat erythrocytes (less than 1:8). Titers obtained with sera from specific pathogen-free swine were 2- to 16-fold lower than those of conventional swine, but were of a similar distribution with regard to the species of erythrocyte tested. Germfree swine sera uniformly exhibited HA titers less than 1:4 against all species of erythrocytes. The majority of these hemagglutinins were immunoglobulin M class but there were some agglutinins of immunoglobulin A class and a slight amount of immunoglobulin G class. Specificity of these agglutinins was examined by absorption tests. The results are consistent with the hypothesis that natural hemagglutinins develop due to dietary or microbial antigenic stimulation, or both.     

Immunohistochemical expressions of cytokeratins, mucin core proteins, p53, and neuroendocrine cell markers in epithelial neoplasm of appendix

Epithelial neoplasms of appendix are infrequent, and their pathological features are not fully characterized. We collected 33 cases of appendiceal tumors and examined immunohistochemically the expression of cytokeratins (CK, CK7, and CK20), mucin core protein (MUC1, MUC2, MUC5AC, and MUC6), E-cadherin, chromogranin A, and p53 protein. Gene analysis of TP53 was also conducted on exons 5 to 8. Clinically, mucinous tumors were predominant in females. Immunohistochemically, all the tumors expressed CK20, whereas CK7 was positive in one third of the cases. Similarly, MUC2 was expressed in all the tumors, whereas MUC1 and MUC5AC were detected in about a half of the cases. Although chromogranin A-positive cells are generally sparse in normal appendix, they were more common in mucinous tumors than in nonmucinous tumors. Contrary to the previous data reported (Mod Pathol 2002;15:599-605), mucinous carcinoma exhibited a higher frequency of p53-positive cells (mean 29%) compared with mucinous adenoma (2.8%) (P < .001), whereas nonmucinous tumors showed high levels of p53-positive cells to similar extent (51%-67%) in both adenoma and carcinoma. The high expression of p53 protein coincided with the presence of mutations in multiple sites of TP53 gene in mucinous tumors. This is the first report that characterized the immunophenotypic profile of appendiceal epithelial neoplasms with an emphasis of a higher frequency of p53 positivity in mucinous carcinoma cases compared with mucinous adenoma in the appendix.     

The Natural History of Neuroblastic Cells in the Fetal Adrenal Gland

A study was made of neuroblastic nodules of the human adrenal gland in fetal life to determine their embryonic morphology and derivation. One hundred sixty-nine glands from 92 fetuses selected from 106 consecutively submitted fetuses formed the basis of this study. All adrenal glands examined contained neuroblastic nodules. They increased in number and maximum size with increasing age, peaked at 17 to 20 weeks gestational age, and regressed in the oldest fetuses. It is concluded that such neuroblastic nodules are an integral part of the normal morphogenesis of the adrenal gland. Their presence at birth and early infancy may represent a normal variation, and they do not necessarily constitute microscopic incipient malignancy.     

gamma-Aminobutyric acid-induced response in rat dissociated paratracheal ganglion cells.

1. The pharmacologic properties of gamma-aminobutyric acid (GABA)-induced Cl- current (ICl) were studied in the paratracheal ganglion cells freshly dissociated from 7- to 10-day-old rat trachea in a whole-cell recording mode by the use of a conventional patch-clamp technique. 2. GABA- and muscimol-induced currents increased sigmoidally in a concentration-dependent manner, and both currents reversed at approximately -3 mV, which was close to the Cl- equilibrium potential (ECl). 3. Strychnine (STR) at low concentration and bicuculline (BIC) inhibited GABA response competitively, whereas STR at the higher concentrations, benzylpenicillin (PCG), or picrotoxin (PTX) inhibited noncompetitively. Inhibition of GABA response by PCG but not other antagonists was voltage dependent, indicating that PCG acts as a Cl- channel blocker. 4. The concentration-response curve of pentobarbital sodium (PB)-induced ICl was bell shaped. At concentrations higher than 10(-3) M, both the peak and plateau currents decreased, and a transient "hump" current appeared immediately after washing out PB. In the presence of PB, the concentration-response curve of GABA shifted toward left without changing the maximum response. 5. Although diazepam (DZP) at concentration used did not induce a response, it potentiated the GABA response in a concentration-dependent manner between 10(-8) and 10(-6) M. DZP also caused a parallel shift toward left in the concentration-response curve of GABA. 6. PB or DZP further enhanced the GABA response in the presence of the other agent. 7. It is concluded that the properties of GABAA receptors in the paratracheal ganglion cells are essentially similar to those reported in other preparations.     

Changes in immune function following surgery for esophageal carcinoma.

Changes in immune function due to surgical injury have been well-documented. Immunosuppression is one of the causes of infectious complications leading to organ dysfunction in critical illness. It is not known what kind of surgery in the daily clinical practice causes immunosuppression. Stress response and immune function following surgery for esophageal carcinoma, assuming a highly-stressed operation, were studied and then compared with the stress response and immune function following gastric surgery, a moderately-stressed procedure. Forty patients who underwent esophagectomy and 39 patients receiving gastric operation were studied. The concentrations of serum interleukin-6 (IL-6) were measured preoperatively, at 1, 2, and 6 h, and at 1, 3, and 10 d after operation. Total protein, serum albumin, rapid turnover protein, serum CRP, and cortisol were measured before operation and at 1, 3, 7, and 21 d after operation. ConA- and PHA-stimulated lymphocyte proliferation, IgA, IgG, and IgM were also measured preoperatively, and on 7 and 21 d following surgery. The patients were fed exclusively by total parenteral nutrition (TPN). A striking rise of IL-6 was observed, with a peak in both groups at 1 to 6 h following operation. The peak values were 419+/-30 pg/mL, which was approximately twice as high in the esophagectomy patients as in the gastrectomy patients (195+/-40 pg/mL). CRP and cortisol also increased after operation, and these increases were also significantly greater in the esophagectomy patients. ConA- and PHA-stimulated lymphocyte proliferation decreased significantly 7 d after esophagectomy (P<0.05), but was unchanged in the patients receiving gastrectomy. Suppression of cellular immunity correlated significantly with serum cortisol, and was preceded by a rise in serum IL-6. The IgA, IgG, and IgM levels, however, remained unchanged from their preoperative values throughout the study in both groups. Nutritional status in terms of serum protein, albumin, and rapid turnover protein, decreased postoperatively, but there was no difference between the two groups. It is, therefore, concluded that cell-mediated immunosuppression, preceded by a hyperinflammatory response, is an observable reaction in patients following esophageal surgery, but not in patients undergoing gastric surgery.     

Device Landing Zone Calcification Predicts Significant Paravalvular Regurgitation after Transcatheter Aortic Valve Replacement: A Real Time Three‐Dimensional Transesophageal Echocardiography Study

Paravalvular regurgitation (PVR) after transcatheter aortic valve replacement (TAVR) is one of the major complications with negative clinical prognosis. Therefore, its prediction is important for further improvement of the outcome. We present a case with TAVR, in which we successfully evaluated aortic valve calcification protruding inward and into the left ventricular outflow tract by real time three‐dimensional transesophageal echocardiography, and predicted significant PVR after the procedure. In conclusion, device landing zone calcification protruding inward is a key for the prediction of significant PVR after TAVR.