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G H Yu

Publications and source records attributed to G H Yu.

At least 19 recordsLinked to original sources

Changing clinical course of patients with malignant mesothelioma: implications for FNA cytology and utility of immunocytochemical staining.

The diagnosis of both local recurrences and distant metastases of mesothelioma can be accomplished by fine-needle aspiration (FNA) biopsy. Although the previous history of mesothelioma provides strong support for recurrent/metastatic mesothelioma, other diagnostic possibilities (particularly adenocarcinoma) may require exclusion via special stains in some cases. In this study, we report on the morphologic findings in 13 cases of mesothelioma which underwent FNA (7 metastatic lesions, 6 local recurrences). In addition, immunohistochemical staining results for 7 cases with available material using antibodies directed against cytokeratin AE 1/3 and two antibodies reported to show consistently positive results in mesothelioma (calretinin and cytokeratin 5/6) are reported and compared to results seen for 10 cases of adenocarcinoma. All cases of mesothelioma and adenocarcinoma showed strong staining with cytokeratin AE 1/3. Three of 7 cases of mesothelioma showed strong staining with calretinin, while only focal staining was detected in 3 additional cases; only one case showed positive staining with cytokeratin 5/6. One of 10 cases of adenocarcinoma showed calretinin positivity; however, at least focal staining with cytokeratin 5/6 was seen in 4 cases. These results suggest that cytokeratin 5/6 is neither a sensitive nor specific stain for the diagnosis of mesothelioma in cytology material. Calretinin appears to be more specific for mesothelioma but showed disappointing sensitivity for this tumor, potentially limiting its diagnostic utility in FNA material.

Aged↗

Adenocarcinoma in colonic brushing cytology: High-grade dysplasia as a diagnostic pitfall.

Cytologic evaluation of brushing specimens obtained from the colon may be useful in the diagnosis of neoplastic and inflammatory lesions, as previous studies have reported favorable sensitivity and specificity figures for this procedure. In this study, we report our experience with 80 colonic brushings examined over a 5-yr period. Thirty cases received an atypical or malignant cytologic diagnosis. Nineteen of 20 cases diagnosed cytologically as adenocarcinoma revealed adenocarcinoma on biopsy; one case showed only adenomatous epithelium on biopsy and subsequent resection. Cases diagnosed cytologically as "atypical" or "adenomatous" showed adenocarcinoma, adenoma, and inflammatory conditions upon biopsy. Slides from 30 atypical/malignant cases were retrospectively reviewed for a number of cytomorphologic features and were correlated with the histologic diagnosis. Cases from histologically confirmed adenocarcinoma tended to show greater degrees of altered nuclear polarity, nuclear pleomorphism, membrane irregularities, and chromatin pattern alterations than those from histologically proven adenomatous or inflammatory lesions. The most likely cause of a false-positive diagnosis in this setting is sampling of an adenoma with high-grade dysplasia which fails to meet histologic criteria for adenocarcinoma (invasion of the underlying muscularis mucosae). Thus, in the second part of the study, we examined histologic sections from surgically excised adenomas to determine the frequency with which profound nuclear atypia is at least focally present, potentially resulting in a false-positive cytology diagnosis upon brushing. Slides from 51 cases were reviewed; cytologic atypia beyond that typically observed in adenomas was not observed in 43% of cases. However, profound nuclear atypia was present in 6% of cases; cytologic evaluation of a brushing specimen from these lesions may have resulted in a false-positive diagnosis of adenocarcinoma, despite the histologic diagnosis of adenoma with severe dysplasia. The remaining cases demonstrated intermediate degrees of atypia. These findings serve to quantitate the frequency with which cytohistologic discrepancies might be expected for mass lesions of the colon.

Adenocarcinoma↗

Blends of stearyl poly(ethylene oxide) coupling-polymer in chitosan as coating materials for polyurethane intravascular catheters.

To optimize the surface biocompatibility of the intravascular catheter, an amphiphilic coupling-polymer of stearyl poly (ethylene oxide) -co- 4,4'-methylene diphenyl diisocyanate-co- stearyl poly (ethylene oxide), for short MSPEO, was specially designed as the surface modifying additive (SMA). The blend of MSPEO in chitosan was coated on the outer wall of the catheters by the dip-coating method. The surface analysis was carried out by ATR-FTIR and contact angle measurements. The surface enrichment of MSPEO was confirmed. On the water interface, the larger the molecular weight of PEO was, the higher the surface enrichment. While on air interface, the case was the contrary. Three kinds of static test of clotting time, plasma recalcification time (PRT), prothrombin time (PT), and thrombin time (TT), as well as the static platelet adhesion experiment were carried out. The results indicated that the coated surface could resist the clotting effectively. In order to test the blood-compatibility of the coated catheters under a shear of blood flow, the dynamic experiment was performed through a closed-loop tubular system with the shear rate of 1500 s(-1). The results of blood regular testing at six different times (0, 5,10, 20, 30, and 60 min) indicated that the biocompatibility of the coating was nearly ideal. Finally, the SMA-MSPEO was proved to be non-chronic-toxic by animal experiments with rats and suitable as a coating material for clinical use.

Animals↗

Surface coating of stearyl poly(ethylene oxide) coupling-polymer on polyurethane guiding catheters with poly(ether urethane) film-building additive for biomedical applications.

Three types of stearyl poly(ethylene oxide) (SPEO) with Mn of 2,300, 6,000 and 12,000 were synthesized; accordingly, three types of amphiphilic coupling-polymer SPEO-MDI-SPEO (MSPEO) were prepared by the reactions with 4,4'-methylene diphenyl diisocyanate (MDI). As the surface-modifying additives (SMA), MSPEOs were coated onto the outer wall of the medical guiding catheters. Due to the lack of stability, when coated, MSPEO blended with the film building agent (FBA), poly(ether urethane) (PEL). The process of coating was performed with a lifter. With invariable speed, the PU guiding catheter was vertically dipped into the coating mixture of SMA-MSPEO and FBA-PEL. The surface analysis was carried out by ATR-FTIR and contact angle measurements. It was proved that the surface enrichment of PEO on water interface was much higher than that on air interface. Three kinds of static clotting time tests, PRT, PT and TT, as well as the static platelet adhesion experiment were performed. The results indicated that the coated surface could resist the blood coagulation effectively. In order to test the blood compatibility of the coated catheters under a shear of blood flow, the dynamic experiment was performed with a closed-loop tubular system under a shear rate of 1,500 s(-1). The blood regular testing was carried out on the samples taken out at six different times (0, 5,10, 20, 30 and 60 min). The results were ideal. Finally, the SMA-MSPEO was proved to be non-acute-toxic by LD50 test.

Blood Coagulation↗

Heterologous activation of protein kinase C stimulates phosphorylation of delta-opioid receptor at serine 344, resulting in beta-arrestin- and clathrin-mediated receptor internalization.

The purpose of the current study is to investigate the effect of opioid-independent, heterologous activation of protein kinase C (PKC) on the responsiveness of opioid receptor and the underlying molecular mechanisms. Our result showed that removing the C terminus of delta opioid receptor (DOR) containing six Ser/Thr residues abolished both DPDPE- and phorbol 12-myristate 13-acetate (PMA)-induced DOR phosphorylation. The phosphorylation levels of DOR mutants T352A, T353A, and T358A/T361A/S363S were comparable to that of the wild-type DOR, whereas S344G substitution blocked PMA-induced receptor phosphorylation, indicating that PKC-mediated phosphorylation occurs at Ser-344. PKC-mediated Ser-344 phosphorylation was also induced by activation of G(q)-coupled alpha(1A)-adrenergic receptor or increase in intracellular Ca(2+) concentration. Activation of PKC by PMA, alpha(1A)-adrenergic receptor agonist, and ionomycin resulted in DOR internalization that required phosphorylation of Ser-344. Expression of dominant negative beta-arrestin and hypertonic sucrose treatment blocked PMA-induced DOR internalization, suggesting that PKC mediates DOR internalization via a beta-arrestin- and clathrin-dependent mechanism. Further study demonstrated that agonist-dependent G protein-coupled receptor kinase (GRK) phosphorylation sites in DOR are not targets of PKC. Agonist-dependent, GRK-mediated receptor phosphorylation and agonist-independent, PKC-mediated DOR phosphorylation were additive, but agonist-induced receptor phosphorylation could inhibit PKC-catalyzed heterologous DOR phosphorylation and subsequent internalization. These data demonstrate that the responsiveness of opioid receptor is regulated by both PKC and GRK through agonist-dependent and agonist-independent mechanisms and PKC-mediated receptor phosphorylation is an important molecular mechanism of heterologous regulation of opioid receptor functions.

Arrestins↗

Fine-needle aspiration of cystic parotid glands lesions: an institutional review of 46 cases with histologic correlation.

BACKGROUND: Many case reports describing various benign and malignant disease entities diagnosed in cystic parotid gland lesions by fine-needle aspiration (FNA) exist in the literature. Very few studies, however, discuss the efficacy and the diagnostic difficulties of FNA cytology in such lesions. The authors report a 5-year institutional experience with FNA cytology of cystic parotid gland lesions and address the accuracy of the procedure and avoidance of diagnostic pitfalls. METHODS: A retrospective review of 46 cases in which patients clinically presented with cystic parotid gland lesions was done from a total of 221 parotid FNAs performed over a 5-year period at the University of Pennsylvania Medical Center. The clinical features, cytology, and follow-up surgical pathology were reviewed to determine diagnostic accuracy and highlight potential pitfalls. RESULTS: Based on subsequent surgical excision in 29 of the 46 cases of cystic parotid gland lesions, a diagnostic accuracy rate of 83% was obtained for FNA. Approximately 20% (9 of 46 cases) were found to be clinically significant tumors and included 4 mucoepidermoid and 1 adenocarcinoma (NOS), 3 benign mixed tumors, and 1 metastatic melanoma. Three major factors were implicated as diagnostic pitfalls in our series: 1) failure to obtain critical clinical information, 2) overinterpretation of paucicellular specimens, and 3) failure to realize that certain tumors generally perceived as solid masses can present clinically as cystic lesions. CONCLUSIONS: FNA cytology is a valuable tool in the primary diagnosis and management of cystic parotid gland lesions. The diagnostic accuracy of this procedure can be significantly improved by acquiring a detailed clinical history, obtaining an adequate cellular specimen, and having knowledge of the variety and frequencies of possible diagnostic entities that may present as cystic parotid gland lesions.

Adult↗

Diagnosis and classification of lymphoma based on cytospin preparations: a comparison of hematopathologists and cytopathologists.

The diagnosis of malignant lymphoma based on cytologic preparations is a source of much debate. The purpose of this study was to assess the ability of a number of pathologists to diagnose and classify lymphoma using cytospin preparations, and to compare the rate of agreement between cytopathologists and hematopathologists. One hundred twenty-five cytospins prepared from histologically confirmed hematologic lesions were examined retrospectively and independently by four hematopathologists/fellows and two cytopathologists without knowledge of the final diagnosis; the results were compared with the final diagnoses derived from histology and immunophenotyping. Eighty-one cases were histologically diagnosed as lymphoma (including 67 cases of B-cell non-Hodgkin's lymphoma), and 44 cases represented a reactive process histologically. The distinction of a malignant from a benign process was made in 75% of the cases by cytospin examination, with cytopathologists correctly diagnosing 75% and hematopathologists 76% of the cases. The accuracy rate for subclassification of the lymphoma cases was 49% (46% for cytopathologists, 52% for hematopathologists). The cytopathologists correctly recognized large-cell lymphoma at an increased frequency compared with the hematopathologists (70% vs. 56%, P = 0.11), while the hematopathologists showed a greater ability to recognize and classify nonfollicle center low-grade B-cell lymphomas (57% vs. 28%, P = 0.01). We conclude that cytopathologists and hematopathologists generally achieve similar accuracy rates in the morphologic evaluation of cytologic preparations of lymphoid lesions, though some differences in their performance do exist.

Biopsy, Needle↗

Intercellular adhesion molecule expression in ductal carcinoma of the breast: correlation of immunohistochemical staining with cytologic smear pattern.

Recent studies suggest that altered expression of intercellular adhesion molecules (ICAM) in ductal carcinoma of the breast is associated with a higher incidence of metastases and decreased patient survival. In addition, the presence of significant cellular dyscohesion in cytologic smear preparations has been found to correlate with the presence of regional and distant metastases in a subset of patients. In this study, we correlate the smear pattern in preparations taken directly from surgically excised breast tumors with their immunohistochemical staining pattern, using antibodies directed against a panel of ICAM. We found excellent correlation, as all three tumors with an extremely high degree of tumor cell cohesion showed strong staining with all ICAM antibodies in the vast majority (>/=90%) of tumor cells in corresponding tissue sections. In contrast, five tumors displaying a largely dyscohesive smear pattern demonstrated decreased staining (</=70% of tumor cells) with at least one of the ICAM antibodies used. Tumors with intermediate degrees of cellular cohesion in smear preparations showed varied patterns of ICAM staining. These findings support the theory that loss of ICAM expression represents the physiologic basis for patterns observed in cytologic smears of ductal carcinoma of the breast.

Adult↗

Evaluation of mild-to-moderate dysplasia on cervical-endocervical (Pap) smear: a subgroup of patients who bridge LSIL and HSIL.

The Bethesda System recommends Pap smear diagnosis to be based on the most abnormal cells present, regardless of number. Our reporting system includes a diagnostic category of mild-to-moderate dysplasia (D1-2), defined as cases with only a few moderately dysplastic cells. We evaluated the validity of a D1-2 diagnostic category by reevaluation of 58 cases with subsequent follow-up (up to 24 months). On biopsy and/or Pap smear follow-up, 24 cases (41%) showed LSIL and 34 cases (59%) showed HSIL. Index smears from these cases were examined by two cytopathologists blinded to patient follow-up for the following morphologic features: volumes (scale 1-4) of LSIL, HSIL, and dyskeratosis, HSIL as single cells or syncytial fragments, and acute inflammation. None of the morphologic features evaluated were significantly different between the LSIL and HSIL follow-up groups based on univariate and multivariate logistic regression analysis. The diagnosis of D1-2 on Pap smear is a valid diagnostic category that defines a subgroup of patients with both LSIL and HSIL follow-up, which cannot be reliably predicted based on morphology alone.

Biopsy↗

Follow-up of morphologically reactive lymphoid proliferations in fine-needle aspirates of elderly patients.

Fine-needle aspiration (FNA) is an effective tool in evaluating the cause of lymphadenopathy. While the morphologic diagnosis of a reactive lymphoid proliferation is common in younger patients, this diagnosis should be made carefully in older patients (those over the age of 50 yr) in light of the facts that such purely reactive conditions occur much less frequently in this population, and that follow-up of these patients reveals a malignancy (usually lymphoma) in a significant number of cases. In this series, we identified 40 patients with a morphologic diagnosis of reactive lymphoid proliferation on FNA and obtained their follow-up information. Of 19 patients under the age of 50 yr, 5 underwent subsequent biopsies and only one revealed a definitive malignancy (5%). In contrast, 7 of 21 patients over the age of 50 yr underwent a subsequent biopsy, and 6 were found to have a malignancy (5 malignant lymphomas, 1 metastatic melanoma). The higher rate of positive follow-up (29%) in this age group supports previous suggestions that morphologically reactive (mixed) lymphoid proliferations be viewed with increased suspicion in the elderly patient, and that additional studies, such as flow cytometry, be performed when material is available.

Adolescent↗

Developmentally regulated expression of two MADS-box genes, MdMADS3 and MdMADS4, in the morphogenesis of flower buds and fruits in apple.

Two MADS-box genes, MdMADS3 and MdMADS4, were isolated from the apple (Malus x domestica Borkh.) cultivar Fuji, and their spatial and temporal expression patterns were studied during morphological differentiation of the flower buds and the fruits. Both MdMADS3 and MdMADS4 showed high sequence similarities to FBP2 from petunia, TM5 from tomato, and AGL2, AGL4 from Arabidopsis. Although MdMADS3 was expressed in the inner three whorls of the floral primordium, its expression was hardly detectable in developing fruit. The second gene, MdMADS4, was ubiquitously expressed in the inflorescence meristem, floral meristem, all four floral organs, and fruit. Moreover, MdMADS4 expression was high in the vascular bundles assigned to the floral tube and the carpellary vascular bundles in fruit at early developmental stages. The MdMADS4 transcript also accumulated in embryos of the developing seeds. These results suggest that MdMADS3 and MdMADS4 are involved in different functions, and that MdMADS4 may function in the important events controlling flower and fruit development.

Amino Acid Sequence↗

Occurrence of intercellular spaces (windows) in metastatic adenocarcinoma in serous fluids: a cytomorphologic, histochemical, and ultrastructural study.

The application of cytomorphologic criteria to the examination of serous effusions allows the reliable diagnosis of malignancy in the majority of cases. One feature observed in tissue fragments previously thought to be indicative of mesothelial origin is the presence of intercellular windows, presumably due to long surface microvilli. In this study, however, we examined cytologic preparations of 143 effusion and body-cavity washing specimens and noted distinct intercellular window formation within tissue fragments of adenocarcinoma in 13% of the cases studied. Stains for mucicarmine, Alcian blue with hyaluronidase pretreatment, and periodic acid-Schiff following diastase digestion on corresponding cell block material demonstrated that intercellular mucin contributes to such window formation in greater than half of these cases. Thus the presence of intercellular windows within tissue fragments does not, in isolation, preclude the diagnosis of malignancy in serous effusions.

Adult↗

Papillary formations in metastatic melanoma.

Cytomorphologic features of melanoma can be extremely variable, in that they can mimic other poorly differentiated neoplasms. Ten cases of metastatic melanoma with distinct, cohesive, papillary tissue fragments observed in fine-needle aspiration (FNA) specimens are reported. These papillary fragments exhibited a central fibrovascular core with attached tumor cells, in a background of single scattered malignant cells, macrophages, and focal necrosis. The aspiration sites included regional or distant palpable lymph nodes, pancreas, bone, and skin. Nine cases had a histologic diagnosis of primary cutaneous melanoma, and in one case the primary skin tumor was detected after the diagnosis was established by FNA of the metastasis. Immunohistochemical studies (S-100 protein, HMB-45 antigen, and factor VIII) were performed in four cases, and electron microscopy in one, confirming the diagnosis of melanoma. An awareness of this cytomorphologic variation of papillary formations in cytology preparations from metastatic melanoma is important and can prevent potential inaccurate interpretation.

Adult↗

Cytomorphology of metastatic mesothelioma in fine-needle aspiration specimens.

The morphologic features of mesothelioma occurring in serous fluids, as well as fine-needle aspiration (FNA) of primary tumors, have been extensively described. Descriptions of the FNA findings in metastatic lesions of mesothelioma, however, are limited to single cases. In this report, we illustrate the cytomorphologic features of four cases of metastatic mesothelioma which underwent FNA, and one additional cytologic preparation taken from a surgically-excised metastatic lesion. The cytomorphologic features of metastatic mesothelioma varied greatly among individual cases with respect to the degree of nuclear pleomorphism, amount of cytoplasm, and degree of cellular cohesion. However, one feature which was consistently seen was the presence of numerous distinct, uniformly small intracytoplasmic vacuoles, believed to represent intracellular fat and glycogen. These morphologic features are illustrated, and the differential diagnosis of intracytoplasmic vacuoles within epithelioid tumor cells in primary and metastatic lesions is discussed.

Aged↗

Immunohistochemical detection of cytotoxic lymphocytes in malignant serous effusions.

The use of ancillary techniques to aid in the diagnosis of metastatic carcinoma in serous effusions has been the subject of numerous studies. In this article, we study 35 cases of malignant effusions (metastatic adenocarcinoma) and 20 benign effusions using a panel of immunohistochemical markers to determine whether changes in the subpopulations of accompanying lymphoid cells can be detected with this technique and whether such changes are associated with the presence of malignancy. We noted a significant increase in cytotoxic lymphocytes, defined as the percentage of all lymphoid cells staining with an antibody to TIA-1 (an antigen localized to the cytotoxic granule membranes of cytotoxic T cells and natural killer cells) in malignant compared with benign effusions (23% vs. 12%; P < 0.05). In addition, nearly all cases in which cytotoxic lymphocytes composed > 20% of the lymphoid cell population contained metastatic tumor. Thus, immunohistochemical staining for TIA-1 can reliably detect cytotoxic lymphocytes in cell blocks of serous effusions; in addition, a relative increase in their number is associated with the presence of malignancy.

Adult↗