Specific IgG to gelatin in children with systemic immediate- and nonimmediate-type reactions to measles, mumps and rubella vaccines.

We examined anti-gelatin IgG in sera of children who suffered from systemic adverse reactions upon immunization with gelatin-containing live virus vaccines. In the group of 30 children who had immediate-type reactions and anti-gelatin IgE, 30 (100%) had anti-gelatin IgG and 29 (96%) had anti-gelatin IgG4. In another group of 75 children who had nonimmediate-type reactions and no anti-gelatin IgE, 22 (29%) had anti-gelatin IgG and six (8%) had IgG4. The IgG positivity well correlated with the lymphocyte proliferation assay positivity. In contrast, as a negative control, all 24 children who had no allergic reaction to live virus vaccines had no anti-gelatin IgG and IgG4. The results suggest that immune-response to gelatin may play a role in the pathogenesis of systemic nonimmediate-type reactions to the live virus vaccines.     

Immunohistochemical and ultrastructural analysis of dysplastic epithelium of human ocular surface: basement membrane and intermediate filament.

PURPOSE: The dysplastic corneal epithelium is characterized by the abnormal proliferation of epithelial cells. The phenotypes of these cells have not been elucidated. We investigated whether such epithelium expresses the phenotypes of corneal or conjunctival epithelial cells. METHODS: The corneas and conjunctivae from four normal subjects and from one patient with epithelial dysplasia of the central cornea were immunostained for IV and VII collagens and for cytokeratins. Monoclonal antibodies against collagen IV reacted to the [alpha1(IV)]2alpha2(IV) or alpha5(IV) molecule. Anti-cytokeratin antibodies were used to define epithelial cell types. The ultrastructure of the basement membrane (BM) of each specimen also was examined. RESULTS: Type VII collagen immunoreactivity was detected in all the specimens of epithelial BM. The anti-collagen IV [alpha1(IV)]2alpha2(IV) antibody labeled the conjunctival BMs, not the BMs of the corneal epithelia, of each subject. The normal corneal epithelial BM, not the BM of the conjunctival or dysplastic corneal epithelium, was immunolabeled with anti-alpha5(IV) antibody. The pattern of cytokeratin expression in the corneal epithelial dysplasia resembled that seen in the normal conjunctivae. Small breaks in the BM of dysplastic corneal epithelium were ultrastructurally revealed. The number of hemidesmosomes in the dysplastic corneal epithelium was decreased as compared with that in the normal BM. CONCLUSION: The composition of collagen types within the BM and the cellular phenotype of the dysplastic epithelium in the cornea resembled those of conjunctival epithelium, not of the cornea.     

In vitro antiplatelet profile of FR171113, a novel non-peptide thrombin receptor antagonist

We have examined the potency of several adenosine receptor antagonists at adenosine A₁ and A_2A receptors using quantitative autoradiography and have compared the results with those of previous studies using the same radioligands in membrane preparations. The agonists [³H]cyclohexyladenosine and [³H]2-[p-(2-carbonylethyl)-phenylethylamino]-5′-N-ethylcarboxamido adenosine ([³H]CGS 21680) were used as radioligands for the two receptors. The results show that 1,3-dipropyl-8-cyclopentyl xanthine (DPCPX) is almost 1000-fold and 8-chloro-4-cyclohexyl-amino-1-(trifluoromethyl)[1,2,4]triazolo[4,3-a] quinoxaline (CP-68,247) about 300-fold more potent at adenosine A₁ receptors in cortex and striatum than at striatal adenosine A_2A receptors. Conversely, 5-amino-7-(2-phenylethyl)-2-(2-furyl)-pyrazolo-[4,3-e]-1,2,4-triazolo [1,5-c]pyrimidine (SCH 58261) is approximately 1000-fold and 4-(2-[7-amino-2-(2-furyl) [1,2,4]-triazolo[2,3-a][1,3,5]triazin-5-yl amino]ethyl)phenol (ZM 241,385) about 400-fold more potent at adenosine A_2A than at A₁ receptors. Caffeine and its metabolites did not show any selectivity. Other studied antagonists were non-selective or showed a modest (20- to 40-fold) adenosine A_2A receptor selectivity. Thus, only a few of the antagonists show such high selectivity that it is not offset by differences in drug distribution and levels of receptor subtype expression.     

Effects of activation of renal adenosine A2 receptor on renal function and renin release in dogs.

Direct effects of adenosine A2 receptor activation on renal function were examined in dogs. When renal perfusion pressure was maintained constant at 100 mmHg, renal administration of a selective A2 receptor agonist, CGS 21680C (sodium salt of CGS 21680, 2-[p-(2-carboxyethyl) phenethylamino]-5'-N-ethylcarboxamido adenosine) (1 microg x kg(-) x min (-1)), although it decreased blood pressure by 20 mmHg, increased renal blood flow and renin release, whereas glomerular filtration rate and urine flow were unaffected. These results suggest that stimulation of renal A2 receptor led to both afferent and efferent arteriolar dilatation, whereas renal A2 receptor plays a minor role in urine formation. CGS 21680C induced renin release and tachycardia that were blocked by propranolol, indicating these effects of A2 receptor stimulation appeared to be indirect.     

Immunolocalization of prolyl 4-hydroxylase in fibroblasts cultured from Tenon's capsule of humans

Background: The excessive accumulation of extracellular matrix (ECM) with the repopulation of fibroblasts may lead to an unsuccessful outcome of glaucoma filtering surgery. We examined the immunolocalization of ECM components and prolyl 4-hydroxylase, an enzyme involved in collagen biosynthesis, in cultured Tenon's capsule fibroblasts (TCFs) of humans to evaluate the production of ECM in the cells. Methods: We used light microscopy to evaluate the immunolocalization of prolyl 4-hydroxylase and ECM components, collagen types I, III, and IV, cellular fibronectin, and laminin in TCFs. Ultrastructural localization of the enzyme was also evaluated by electron microscopy. Results: Immunoreactivity with monoclonal antibodies against the and subunits of the enzyme or with the polyclonal antibody against it was detected in the cytoplasm of the cells in a fine granular pattern, indicating its localization in the indoplasmic reticulum (ER). Immunoreactivity for the enzyme was detected in the cisternae of the ER on electron microscopy. Types I and III collagen reactivities were also observed in the cytoplasm in a fine granular pattern. T reactivity was present diffusely on the cell surface. The distribution of laminin reactivity in the cytoplasm resembled that of types I and III collagen. Cellular fibronectin reactivity was observed in the ECM in a reticular pattern. Conclusion: Prolyl 4-hydroxylase was located in the cisternae of the ER. TCFs produced a variety of ECM components in vitro. The results provide insight into the fibrotic process during scar formation at the site of a bleb following filtering surgery.     

Purification and Partial Characterization of an Indomethacin Hydrolyzing Enzyme from Pig Liver

Purpose. Indomethacin is well known to be metabolized via O-demethylation and N-deacylation. In this paper we found an enzyme involved in the hydrolysis of amide-linkage of indomethacin and partially characterized it as well as its substrate specificity. Methods. An indomethacin hydrolyzing enzyme was purified to homogeneity from pig liver microsomes using columns of Q-Sepharose, Red-Sepharose and Blue-Sepharose. The enzyme activity was assayed by measuring of -chlorobenzoic acid liberated from indomethacin by HPLC. Results. The purified enzyme effectively hydrolyzed the amide linkage in indomethacin but not those in -naphthylacetate and -nitrophenylacetate, which are typical substrates for carboxylesterase. The subunit molecular mass of the enzyme was 65 kDa according SDS-polyacrylamide gel electrophoresis. The Michaelis constant (Km) and maximum velocity (Vmax) values for indomethacin were 67.8 µM and 9.02 nmol/min/mg protein, respectively. The amino acid sequence analysis of the enzyme after cyanogen bromide cleavage showed high homology with a mouse carboxylesterase isozyme designated as ES-male. The activity of indomethacin hydrolysis was relatively high in the pig, rabbit and human liver homogenate, but not in those from rat and mouse. On the other hand, purified human liver carboxylesterases pl 5.3 and 4.5, and pig liver carboxylesterases have no catalytic activity for indomethacin. Conclusions. These results indicate that the hydrolysis of amide-linkage of indomethacin in humans would be associated with an enzyme similar to the indomethacin hydrolyzing enzyme from pig liver microsomes described here.     

Oxygen uptake and carbon dioxide elimination during epinephrine-induced arrhythmias in humans

Key words  cardiac arrhythmias - oxygen uptake - carbon dioxide elimination     

Comparative cardiovascular effects of SNP,ATP and phentolamine during norepinephrine-induced hypertension in dogs

There has been no study comparing the advantage and disadvantage of various antihypertensive agents during surgery for pheochromocytomas because the study is difficult in clinical setting. In the present experiments using dogs, after increasing the arterial blood pressure with norepinephrine, we decreased it to the baseline with sodium nitroprusside (SNP), adenosine triphosphate (ATP), or phentolamine (PE) and compared the hemodynamic changes. A hyperdynamic state was found with ATP and with PE, but not with SNP. The norepinephrine-induced pulmonary hypertension could be successfully treated with SNP, but not with ATP or PE. The reason for these differences are thought to be the different vasodilative properties on peripheral arteries and veins. We conclude that agents that dilates the arteries and veins should be used to regulate the arterial pressure during surgical removal of a pheochromocytoma.(Murata K, Takahashi H, Ikeda K: Comparative cardiovascular effects of SNP, ATP and phentolamine during norepinephrine-induced hypertension in dogs. J Anesth 5: 396–403, 1991)     

Nasal T-cell lymphoma as a type of so-called "lethal midline granuloma"

Six cases were described in which an initial clinical diagnosis of "rhinitis gangrenosa progressiva" or lethal midline granuloma was made. The histological examinations of their surgical and autopsy specimens proved that their nasologic diseases could all be identified as malignant lymphoma arising from the nasal cavity, showing the general histologic characteristics reported for T-cell lymphomata derived from peripheral T-cells. This histologic observation was then confirmed by immunofluorescence studies using various antisera directed toward either human T- or B-cell-surface antigens. These studies clearly demonstrated that their malignant cells bore human Ly-l-like antigen but lacked human TL-like and Ia-like antigens as well as surface-bound immunoglobulins, indicating their peripheral T-cell origin. These data may suggest that so-called "rhinitis gangrenosa progressiva" or lethal midline granuloma contains at least two distinct disease categories, one of which is Wegener's granulomatosis, and the other of which is nasal T-cell lymphoma as described herein.