Pediatric bronchoscopy

Endoscopic techniques for evaluation and management of airway and pulmonary problems in pediatric patients have matured greatly in the past decade, especially with the introduction of flexible instruments suitable for use in the smallest infants. Careful selection of the most appropriate instrument and technique by well-trained medical or surgical endoscopists will result in safe and effective diagnosis and treatment of a wide variety of conditions affecting the upper and lower respiratory tract.     

Alpha 6 beta 4 integrin and newly deposited laminin-1 and laminin-5 form the adhesion mechanism of gastric carcinoma. Continuous expression of laminins but not that of collagen VII is preserved in invasive parts of the carcinomas: implications for acquisition of the invading phenotype

We studied the expression and distribution of different laminin chains, the alpha 6 beta 4 integrin and type VII collagen, i.e., components of the epithelial adhesion complex, in gastric carcinomas and in suggested preneoplastic stages of this malignancy. Intestinal-type gastric carcinomas showed strong reactivity for laminin alpha 1, alpha 3, beta 1, and beta 3 chains, the components of laminin-1 and -5, at the interface between malignant cells and tumor stroma. The reactivities were continuous throughout the carcinomas, even in structures invading through the smooth muscle layers of the gastric wall. The expression of different laminin chains was accompanied by strong polarized reactivity for the alpha 6 beta 4 integrin, which is a receptor for both laminin-1 and laminin-5. Collagen type VII was only occasionally present at sites showing reactivity for laminin-5 and was totally absent from the cell islands invading through the gastric wall. Intestinalized gastric epithelium showed a similar expression pattern of laminins and the alpha 6 beta 4 integrin as the gastric carcinomas. Our results suggest that gastric carcinomas use the alpha 6 beta 4 integrin and newly deposited laminin-1 and -5, accompanied by the disappearance of type VII collagen, as their mechanism of adhesion during the invasion through surrounding tissues. Unlike in previous studies, the reactivity for the laminin-5 protein was not restricted to the invading cells but surrounded the malignant glandular structures throughout the tumor. Our results also show that both intestinal-type gastric carcinoma, and intestinal metaplasia mimic the gastric surface epithelium in the expression pattern of laminins and the beta 4 integrin subunit. This supports previous studies proposing a pathogenetic sequence from intestinal metaplasia to gastric carcinoma.     

Ovarian small cell tumors: an electron microscopic review

Small cell tumors of the ovary are uncommon but represent an important group to recognize in the differential diagnosis of primary and metastatic ovarian neoplasms. In some cases the correct diagnosis cannot be confidently made on the basis of clinical setting, routine light microscopy, and immunohistochemistry, and electron microscopy may be supportive or definitive in establishing cell type. The cell type is often important in choosing optimal therapy and in predicting prognosis. The authors performed electron microscopy on a moderate number of ovarian small cell tumors and here describe and illustrate the diagnostic features of representative examples of various types. The ultrastructural features of the metastatic tumors, such as embryonal rhabdomyosarcoma, neuroblastoma, and melanoma, are identical to those of their respective primary tumors, are well known, and usually pose no problem in diagnosis. On the other hand, the ultrastructural features of some primary ovarian small cell tumors may present a more difficult differential diagnosis, because they have features that are subtle and/or in common. Exemplary of tumors in this category are diffuse adult granulosa cell tumor, endometrial stromal sarcoma, and small cell carcinomas of the hypercalcemic and pulmonary (oat cell) types. Distinguishing among them may be difficult but is possible, and electron microscopy may be a valuable supplement to the diagnostic information obtained from the clinical presentation, light microscopy, immunohistochemistry and, in some tumors, cytometric analysis of these neoplasms.     

Murine IgG1 complexes trigger immune effector functions predominantly via Fc gamma RIII (CD16)

Previously, we have demonstrated that phagocytosis of IgG1-coated particles by macrophages in vitro is impaired by deletion of Fc gamma RIII in mice, suggesting that IgG1 may interact preferentially with Fc gamma RIII. In the present study, the biologic relevance of this observation was addressed by triggering various effector functions of the immune system in Fc gamma RIII(-/-) mice, using panels of mAbs of different IgG subclasses. Both binding and phagocytosis of IgG1-coated sheep or human erythrocytes by Fc gamma RIII(-/-) macrophages in vitro were strongly impaired, indicating that the impaired ingestion of complexed IgG1 by Fc gamma RIII(-/-) macrophages is due to a defect in binding. An in vivo consequence of the defective phagocytosis was observed by resistance of Fc gamma RIII-deficient mice to experimental autoimmune hemolytic anemia, as shown by a lack of IgG1-mediated erythrophagocytosis in vivo by liver macrophages. Furthermore, trapping of soluble IgG1-containing immune complexes by follicular dendritic cells in mesenteric lymph nodes from Fc gamma RIII(-/-) mice was abolished. Whole blood from Fc gamma RIII(-/-) mice was unable to induce lysis of tumor cells in the presence of IgG1 antitumor Abs. Finally, IgG1 mAbs proved unable to mount a passive cutaneous anaphylaxis in Fc gamma RIII(-/-) mice. Together, these results demonstrate that IgG1 complexes, either in particulate or in soluble form, trigger in vitro and in vivo immune effector functions in mice predominantly via Fc gamma RIII.     

Molecular cloning, expression, and characterization of a novel human serine/threonine protein phosphatase, PP7, that is homologous to Drosophila retinal degeneration C gene product (rdgC)

A novel serine/threonine protein phosphatase (PPase) designated PP7 was identified from cDNA produced from human retina RNA. PP7 has a molecular mass of approximately 75 kDa, and the deduced amino acid sequence of PP7 contains a phosphatase catalytic core domain that possesses all of the invariant motifs of the PP1, PP2A, PP2B, PP4, PP5, and PP6 gene family. However, PP7 has unique N- and C-terminal regions and shares < 35% identity with the other known PPases. The unique C-terminal region of PP7 contains multiple Ca2+ binding sites (i.e. EF-hand motifs). This region of PP7 is similar to the Drosophila retinal degeneration C gene product (rdgC), and PP7 and rdgC share 42.1% identity. Unlike the other known PPases, the expression of PP7 is not ubiquitous; PP7 was only detected in retina and retinal-derived Y-79 retinoblastoma cells. Expression of recombinant human PP7 in baculovirus-infected SF21 insect cells produces an active soluble enzyme that is capable of utilizing phosphohistone and p-nitrophenyl phosphate as substrates. The activity of recombinant PP7 is dependent on Mg2+ and is activated by calcium (IC50 approximately equal to 250 microM). PP7 is not affected by calmodulin and is insensitive to inhibition by okadaic acid, microcystin-LR, calyculin A, and cantharidin.     

2-Azetidinone cholesterol absorption inhibitors: structure-activity relationships on the heterocyclic nucleus

A series of azetidinone cholesterol absorption inhibitors related to SCH 48461 ((-)-6) has been prepared, and compounds were evaluated for their ability to inhibit hepatic cholesteryl ester formation in a cholesterol-fed hamster model. Although originally designed as acyl CoA: cholesterol acyltransferase (ACAT) inhibitors, comparison of in vivo potency with in vitro activity in a microsomal ACAT assay indicates no correlation between activity in these two models. The molecular mechanism by which these compounds inhibit cholesterol absorption is unknown. Despite this limitation, examination of the in vivo activity of a range of compounds has revealed clear structure-activity relationships consistent with a well-defined molecular target. The details of these structure-activity relationships and their implications on the nature of the putative pharmacophore are discussed.     

Data quality review program: the Society of Thoracic Surgeons Adult Cardiac National Database

In summary, the National Database Committee's Audit and Validation Subcommittee is working to maximize the data completeness and quality of the STS National Database. Toward this end, we welcome your suggestions for improvement.