bluuebunny/crossref_metadata_2025_split huggingface dataset:
Host‐vs.‐altered‐host eruptions in patients on liposomal doxorubicin
Authors: Skelton Henry , Linstrum Jill , Smith Kathleen 
Published: March 2003

Background:  Anthracycline antitumor antibiotics are the most commonly used chemotherapeutic agents. One of these is doxorubicin. Liposomal doxorubicin was developed as a drug delivery system in order to deliver the active drug intracellularly while decreasing the systemic toxicity, particularly hematological and cardiac toxicity.Methods:  The clinical and histologic findings of the cutaneous eruptions of associated with liposomal doxorubicin are reviewed.Results: The eruptions occurred in three women with metastatic ovarian carcinoma who were treated with liposomal doxorubicin. These three patients developed erythematous macular/papular to plaque cutaneous lesions, and in one patient a vesicular component. The eruptions involved the trunk and extremities approximately 3–4 weeks after completions of therapy. None of the patients had any documented infections, and none of the patients had symptoms other than pruritus. The eruptions cleared over a period of weeks to months. Histologic features included an interface dermatitis with numerous apoptotic/dyskeratotic cells within the epidermis, with involvement the intra‐epidermal sweat ducts and the infundibulum of hair follicles.Conclusion:  We believe that these eruptions represented a chemotherapy induced host‐vs.‐altered host reaction.
Anaplastic neoplasms arising from basal cellcarcinoma xenotransplants into SCID‐beige mice
Authors: Carlson J. Andrew , Combates Nicholas J. , Stenn Kurt S. , Prouty Stephen M. 
Published: March 2003

Background: An animal model for the study of basal cell carcinoma (BCC) is required to better understand its biology. Several attempts to grow BCC in immuno‐incompetent animals have been only modestly successful. Methods: To test the ability of BCC to grow in a mouse with complete and severe immuno‐incompetence, 14 individual BCC were transplanted into the subcutaneous tissue of 18 SCID‐beige mice (T, B and natural killer cell deficient). Light microscopy and immunophenotypic analyses were performed on primary BCC and first and seventh passage tumors. Results: Transplantation of three BCC yielded rapidly growing anaplastic tumors for a tumor take of 18% (3/18). SCID‐beige mice without tumor growth had mostly scars or epidermoid cysts at the transplant sites. The three patients whose BCC gave rise to the anaplastic tumors were significantly older than those without tumor growth (87 vs. 64, p = 0.001), but they did not differ with respect to BCC type or general health. These three anaplastic tumors were histologically and immunophenotypically similar, being composed of dyscohesive, pleomorphic cells that expressed vimentin and smooth muscle actin. In the first passage mice these tumors were locally invasive, tumor‐forming nodules associated with an expansion of donor inflammatory cells (T and B lymphocytes and plasma cells), rare remnants of BCC epithelium and epidermoid cysts. By the seventh passage, the tumors were homogenous and metastasized widely throughout the mice. Changing transplantation location to the dermis to wound environment or supplementing the tumor with BCC‐derived fibroblasts did not alter the phenotype or growth rate in SCID‐beige mice. Anaplastic tumors also grew easily in SCID mice (T and B cell deficient). However, transplantation of the anaplastic tumors into normal mice (CB‐17) or less severely immunodeficient mice (NCr and Balb/c: T and natural killer cell deficient) did not allow for growth. Furthermore, tumor growth could not be maintained in vitro. Conclusion: Empirically, these data suggest that BCC has the potential to become an aggressive metastatic neoplasm, given the right immune and stromal environment. Moreover, a functional B lymphocyte system appears to prevent this growth. As human lymphocytes also engraft in SCID‐beige mice, the original host immune response could be responsible for the lack of tumor growth in the majority of xenografts. Furthermore, the anaplastic and metastatic phenotype of these BCC derived neoplasms may be the experimental equivalent of metastatic BCC and BCC associated with carcinosarcoma.
A predominant IgG4 subclass may be responsible for false‐negative direct immunofluorescence in bullous pemphigoid
Authors: Buschman Kerry E. , Seraly Mark , Thong H. Y. , Deng Jau‐Shyong , Draviam Rose P. , Abernethy John L. 
Published: March 2003

Background: Bullous pemphigoid (BP) is an immune‐mediated blistering disease, usually characterized immunopathologically by the linear deposition of IgG and C3 along the basement membrane zone (BMZ) of skin. However, positive deposition of C3 but negative staining for IgG on direct immunofluorescence (DIF) studies has been noted in some patients.Methods: Twelve patients known to have BP but with absence of staining for IgG were included in this study. Frozen sections of skin specimens from the 12 patients were subjected to IgG DIF, as well as a sandwich double antibody method of staining for IgG, IgG subclasses, and light chains. Enzyme‐linked immunosorbent assay (ELISA) using commercially available human IgG subclasses was used to analyze the subclass restriction of FITC‐labeled antihuman IgG conjugates.Results:  Of the 12 skin specimens with positive C3 and negative IgG on DIF, nine were positive for IgG with the double antibody sandwich method. In addition, all 12 specimens had positive linear staining for the subclass IgG4 along the BMZ with this method. There was no IgG light chain restriction. Two commercially obtained antihuman IgG conjugates, both commonly used in our laboratory for DIF testing, were analyzed for separate IgG subclass specificity by ELISA. Both conjugates showed high reactivity to IgG1 and IgG3 with less reactivity to IgG2 and IgG4.Conclusion:  These results suggest that the following factors contribute to false‐negative staining for IgG on DIF in some BP patients: (i): subthreshold IgG in skin specimens; (ii) limited reactivity of commercial antihuman IgG conjugates to the IgG4 subclass; and (iii) decreased sensitivity of DIF compared with double antibody methods for the detection of IgG. The use of sandwich double antibody immunofluorescence methods to test for IgG and/or IgG subclasses may be helpful in definitively diagnosing BP in patients with negative IgG and positive C3 staining on DIF.
Human telomerase RNA component expression in Spitz nevi, common melanocytic nevi, and malignant melanomas
Authors: Guttman‐Yassky Emma , Bergman Reuven , Manov Lena , Sprecher Eli , Shaefer Yan , Kerner Hedviga 
Published: March 2003

Background:  Telomerase is a ribonucleoprotein DNA polymerase that is capable of synthesizing telomeres onto the ends of chromosomes. The cumulative loss of telomerase activity is believed to be associated with cell senescence. Telomerase activity has been shown to be higher in malignant melanomas than in common melanocytic nevi. The aim of the present study was to elucidate the pattern of expression of the human telomerase RNA (hTER) component in routinely processed specimens of Spitz nevi, malignant melanomas, and ordinary melanocytic nevi.Methods:  Ten specimens of each type of tumor were studied, using an in situ hybridization technique.Results:  All three types of tumors demonstrated moderate to high intensities of hTER expression, usually in more than half of the tumor cells, and the majority of the studied lesions in each group did not show stratification of staining. The hTER component was also detected in the epidermis, sweat glands, and pilosebaceous units.Conclusions:  hTER levels do not necessarily correlate with the level of telomerase activity, and the level and pattern of hTER expression are not useful as an adjunct to the histologic differential diagnosis of Spitz nevi from melanocytic nevi and malignant melanomas.
h‐Caldesmon as a specific marker of smooth muscle cell differentiation in some soft tissue tumors of the skin
Authors: D'Addario Stephen F. , Morgan Michael , Talley Lori , Smoller Bruce R. 
Published: March 2003

Background:  An existing problem in contemporary pathology is the classification and distinction of spindle cell soft tissue tumors of the skin. Markers such as α‐smooth muscle actin (α‐SMA) and desmin, considered specific for smooth muscle cell (SMC), have been shown to be expressed in a variety of fibroblastic and myofibroblastic processes. High‐molecular‐weight caldesmon (h‐caldesmon), one of two isoforms, is reported to be expressed exclusively by SMC and has recently been shown to be a specific marker of SMC tumors.Methods: Tumors were obtained from 11 patients taken from the surgical pathology archives of the University of South Florida and cases were coded as smooth muscle hamartoma, myofibroma, and dermatomyofibroma.Results:  The case of smooth muscle hamartoma had greater than 90% of tumor cells labeling with anti‐h‐caldesmon antibodies. Three of three cases of myofibroma had focal areas of positivity representing less than 10% of total tumor cells. Seven of seven dermatomyofibromas showed no apparent labeling with anti‐h‐caldesmon antibody. Dense reactivity was noted in vascular wall smooth muscle, indicating internal controls.Conclusions: We can conclude that h‐caldesmon is a specific marker of fully differentiated smooth muscle and that it can serve to differentiate spindled SMC soft tissue tumors of the skin from tumors of myofibroblastic and/or fibroblastic origin.
Three‐dimensional imaging of human skin and mucosa by two‐photon laser scanning microscopy
Authors: Malone Janine C. , Hood Antoinette F. , Conley Tameka , Nürnberger Jens , Baldridge Lee Ann , Clendenon Jeffrey L. , Dunn Ken W. , Phillips Carrie L. 
Published: March 2003

Background: Various structural components of human skin biopsy specimens are difficult to visualize using conventional histologic approaches.Methods: We used two‐photon microscopy and advanced imaging software to render three‐dimensional (3D) images of in situ nerves, blood vessels, and hair follicles labeled with various fluorescent markers. Archived frozen human skin biopsy specimens were cryosectioned up to 150 µm in thickness and fluorescently stained with rhodamine‐ or fluorescein‐labeled antibodies or lectins. Optical sections were collected by two‐photon microscopy and the resulting data sets were analyzed in three dimensions using Voxx software.Results: Reconstructed image volumes demonstrated the complex 3D morphology of nerves, blood vessels and adnexal structures in normal mucocutaneous tissue.Conclusion: Two‐photon microscopy and Voxx rendering software allow for detailed 3D visualization of structures within human mucocutaneous biopsy specimens, as they appear in situ, and facilitate objective interpretation of variations in their morphology. These techniques may be used to investigate disorders involving cutaneous structures that are difficult to visualize by means of traditional microscopy.
Aberrant expression of p16 and RB protein in eccrine porocarcinoma
Authors: Gu Li‐Hong , Ichiki Yoshiro , Kitajima Yasuo 
Published: March 2003

Background:  Eccrine porocarcinoma is a rare malignant tumor of the sweat gland and very little is known about its etiology and molecular basis.Methods:  To investigate the expression of p16 and retinoblastoma (RB) protein and their relationship, an immunohistochemical method was performed on nine eccrine porocarcinomas and five eccrine poromas. Furthermore, one case of eccrine porocarcinoma was analyzed for p16 gene mutation.Results:  A striking inverse correlation between p16 and RB expression was noted in all of the eccrine porocarcinomas and poromas. Strong immunoreactivity for p16 protein was observed in both nuclei and cytoplasm of the tumor cells in eight out of nine cases of eccrine porocarcinomas, while RB expression was negative in these cases. Conversely, one case of eccrine porocarcinoma did not show immunoreactivity for p16 protein, whereas RB protein was positive in the scattered nuclei. On the other hand, immunostaining of p16 was negative in all cases of five poromas, whereas RB‐positive nuclei were sparse. No p16 gene mutation was detected in the investigated eccrine porocarcinoma case.Conclusions:  These results indicate that detectable p16 protein and loss of RB protein are common occurrences in eccrine porocarcinoma lesions. Moreover, overexpression of p16 protein may be an additional, simple and useful diagnostic marker for eccrine porocarcinoma on routine laboratory screening.
Simultaneous development of lymphoplasmacytic lymphoma and diffuse large B‐cell lymphoma – analyses of the clonal relatedness by sequencing CDR3 in immunoglobulin heavy chain genes
Authors: Shimizu Seiichi , Tamagawa Yuna , Kojima Hiroshi , Mori Naoyoshi , Nagata Michio , Noguchi Masayuki , Nagasawa Toshiro 
Published: March 2003

Abstract: A 75‐yr‐old male simultaneously having lymphoplasmacytic lymphoma (LPL) and diffuse large B‐cell lymphoma (DLBCL) is presented. He had manifested with lumbago, high‐grade fever, and confusion. Physical examination on admission showed disorientation and severe back pain. There were neither lymphadenopathy nor hepatosplenomegaly. Routine laboratory tests showed moderate pancytopenia, hypercalcemia (serum calcium, 15.9 mg/dL), IgM λ‐type monoclonal gammopathy (IgG, 405 mg/dL; IgA, 42 mg/dL; and IgM, 2023 mg/dL), and λ‐type Bence–Jones protein in the urine (0.8 g/d). Bone marrow biopsy showed the clusters of surface λ‐positive small‐sized mature‐appearing lymphoplasmacytoid cells. Bone survey and computed tomographic scan showed multiple osteolytic lesions and a tumor involving the third lumbar spine (L3). An open biopsy of the L3 tumor showed diffuse proliferation of CD20‐ and λ‐positive large cells. We thus diagnosed the patient as simultaneously having LPL and DLBCL. Although the combination chemotherapy was at least partially effective, he died of bacteremia and organ failure after three courses of chemotherapy. To clarify the clonal relatedness between LPL and DLBCL, we analyzed the sequences of the complementarity‐determining region 3 in immunoglobulin heavy‐chain genes. The data showed that LPL and DLBCL in the present patient originated from two independent clones.
Cytokine Network of Eutopic and Ectopic Endometrium in Women with Adenomyosis
Authors: SOTNIKOVA NATALIA , ANTSIFEROVA IOULIA , MALYSHKINA ANNA 
Published: March 2003

PROBLEM: Recent studies showed the impairment of local cytokine balance in women with external endometriosis, but similar findings concerning direct production of cytokines by immunocompetent cells of women with adenomyosis are absent. In this context, investigation of the cytokine synthesis by mononuclear cells (MNCs) infiltrating eutopic and ectopic endometrium is of special interest.METHOD OF STUDY: Concentration of interferon‐γ (IFNγ), interferon‐α (IFNα), tumour necrosis factor‐α (TNFα), interleukin‐1β (IL‐1β) and epidermal growth factor (EGF) in supernatants (SNs) of 24‐hr cultures of MNCs obtained from eutopic and ectopic endometrium of women with adenomyosis was determined by enzyme‐linked immunosorbent assay.RESULTS: The levels of IFNγ, IFNα, TNFα, IL‐1β and EGF in SNs of eutopic endometrial MNCs of women with adenomyosis were significantly increased and the content of IL‐8 in SNs was reduced compared with that of the control figures. Ectopic MNCs of women with adenomyosis produced higher levels of IFNγ, IFNα and TNFα than the MNCs of normal endometrium. The production of IL‐1β, IL‐8 and EGF by ectopic endometrial MNCs was significantly reduced.CONCLUSION: The results obtained indicate a significant role of local cytokine production impairment in the development of adenomyosis.
Some Thoughts on the Reproductive Autoimmune Failure Syndrome (RAFS) and Th‐1 Versus Th‐2 Immune Responses
Authors: GLEICHER NORBERT 
Published: March 2003

Gleicher N. Some thoughts on the reproductive autoimmune failure syndrome (RAFS) and Th‐1 versus Th‐2 immune responses. AJRI 2002; 48:252–254 © Blackwell Munksgaard, 2002 PROBLEM: The concept of immunologically induced reproductive failure has remained very controversial. Especially the question whether abnormal immune function can cause infertility has recently been subject to strong disagreement. This opinion piece is an attempt to reconcile difference of opinion by integrating clinical data from the human experience with well‐established experimental models in animals.METHOD OF STUDY: Review of published literature.RESULTS: Experimental animal data, especially in the mouse, have suggested that normal pregnancy requires a switch to an immune response with T helper (Th)‐2 preponderance. Recent data from the human experience suggest that infertility, repeated pregnancy loss and certain complications of pregnancy may be the consequence of abnormal Th‐1 preponderance. In analogy, to animal models, immunologic reproductive failure in humans, may therefore not be the consequence of specific autoantibody abnormalities or natural killer (NK)‐cell abnormalities, but the reflection of a misdirection of a more broadly based immune response.CONCLUSIONS: Under such a model, both diagnosis and treatment of immunologically induced forms of reproductive failure require re‐evaluation. Such a model, however, provides a satisfactory explanation for contradictory findings in the human experience that have led to strong disagreements among investigations.
Prostaglandin D2 and Reproduction
Authors: SAITO SHIGERU , TSUDA HIROSHI , MICHIMATA TOSHIHIKO 
Published: March 2003

This review highlights recent studies investigating the role of prostaglandin (PG)D2 in reproduction. PGD2 induces sleep, allergic responses, inhibition of platelet aggregation, and relaxation of vascular and non‐vascular smooth muscle, and has some roles in reproduction.Two types of PGD2 synthase are known. Lipocalin‐type PGD synthase is present in cerebrospinal fluid, seminal plasma and may play an important role in male reproduction. Another PGD synthase, hematopoietic PGD synthase is present in the spleen, fallopian tube, endometrial gland cells, extravillous trophoblasts and villous trophoblasts, and perhaps plays an important role in female reproduction. Recent studies demonstrate that PGD2 is probably involved in multiple aspects of inflammation through its dual receptor systems, DP and CRTH2. CRTH2 but not DP is a chemo‐attractant receptor for PGD2. Interestingly, CRTH2 is a most reliable marker for the detection of human T helper type 2 (Th2) and T cytotoxic type 2 (Tc2) cells, and the percentages of CRTH expressing CD4+‐T cells and CD8+‐T cells were significantly higher in the decidua especially at the implantation site, suggesting that Th2 and Tc2 cells recruit into the materno–fetal interface, in a PGD2‐mediated manner. PGD2 has a very unique effect to inhibit antigen presentation by inhibition of dendritic cell (DC) migration through DP but not CRTH2. PGD2 might appear to contribute to the maintenance of pregnancy by controlling the Th1/Th2 balance and antigen presentation by DCs through its dual receptor systems, CRTH2 and DP.
Absence of HLA‐G Expression in Macrophages of Human Decidua
Authors: SEDLMAYR PETER , MORALES PEDRO , TRUMMER SILVIA , WASCHER KARIN , AZZOLA DAGMAR , BLASCHITZ ASTRID , HAMMER ASTRID , WALCHER WOLFGANG , WINTERSTEIGER REINHOLD , DOHR GOTTFRIED 
Published: March 2003

PROBLEM: Macrophages – together with natural killer (NK) cells – constitute the majority of bone marrow derived infiltrating cells in the decidua. As interferon‐γ (IFN‐γ), a cytokine produced by NK cells, has been reported to induce expression of human leukocyte antigen (HLA‐G) in monocytic cells, suggesting expression of HLA‐G on decidua macrophages potentially stimulated by IFN‐γ, the question arises whether decidua macrophages in normal pregnancy express HLA‐G.METHOD OF STUDY: The study was based on immunohistochemistry and flow cytometry. In order to exclude that potentially elusive soluble HLA‐G was not detected by immunohistochemistry, we performed in addition RT–PCR of flow‐sorted decidua macrophages.RESULTS: Our findings indicate that HLA‐G is not present on macrophages of first trimester or term decidua in either membrane‐bound or soluble form. Transcripts for soluble HLA‐G1 and ‐G2 were not detected.CONCLUSIONS: We exclude a role of HLA‐G on the surface of decidua macrophages or of soluble HLA‐G1 or ‐G2 as a secretory product of decidua macrophages with regard to interaction with HLA‐G receptors present in or outside the decidua.
IL‐18 is Present at the Maternal–Fetal Interface and Enhances Cytotoxic Activity of Decidual Lymphocytes
Authors: TOKMADZ̆IĆ VLATKA S. , TSUJI YOSHIYUKI , BOGOVIĆ TATJANA , LAŠKARIN GORDANA , CUPURDIJA KRISTIJAN , Š TRBO NATAŠŠA , KOYAMA KOJI , OKAMURA HARUKI , PODACK ECKHARD R. , RUKAVINA DANIEL 
Published: March 2003

Tokmad&#x007a;̆ić VS, Tsuji Y, Bogović T, Laškarin G, Cupurdija K, Štrbo N, Koyama K, Okamura H, Podack ER, Rukavina D. IL‐18 is present at the maternal‐fetal interface and enhances cytotoxic activity of decidual lymphocytes. AJRI 2002; 48:191–200 © Blackwell Munksgaard, 2002 PROBLEM: Perforin expressing uterine natural killer (uNK) cells are under complex cytokine influence. The aim of the study was to investigate the presence and role of interleukin (IL)‐18 on NK cytolytic potential at maternal–fetal (M–F) interface.METHOD OF STUDY: Peripheral blood cells and decidual tissue were obtained from elective pregnancy termination of normal human 6–10‐week‐old pregnancies. Perforin expression and cytolytic activity of peripheral blood (PBL) and decidual lymphocytes (DL) were analyzed by flow cytometry. IL‐18 positive decidual adherent cells (DAC) were detected by the same method. Interleukin‐18 and IL‐18 receptor (IL‐18R) expression on the trophoblastic cells was detected by immunohistology using biotinylated anti‐IL‐18 and IL‐18R monoclonal antibodies.RESULTS: The IL‐18 added in a dose of 10 ng/mL up‐regulates perforin expression and cytolytic activity of DL. Simultaneous stimulation with IL‐18 and IL‐12 enhanced DL cytolytic activity, while IL‐18 combined with IL‐10 or IL‐15 did not show this effect. Cytolytic activity of PBL was up‐regulated by IL‐18 as well, and this effect was enhanced by the addition of IL‐12 and IL‐15. Interleukin‐18 did not affect perforin‐protein expression in cultured PBL. Approximately 20% of DAC were IL‐18 positive and these cells were mostly human leukocyte antigen (HLA)‐DR negative. IL‐18R positive cells were found on syncytiotrophoblast cell layer, interstitial tissue cells of villi and fetal blood cells. There was no detectable IL‐18 staining on trophoblast cell layer on villi, but strong staining of fetal blood cells in villous vessels.CONCLUSION: These are first results showing IL‐18R expression, but not IL‐18 expression on villous trophoblastic cells, as well as enhancement of perforin expression and NK cytolytic potential of DL under the influence of IL‐18. IL‐18 in concert with other cytokines and hormones could play an important role in the regulation of cytolytic potential of first trimester pregnancy decidual and peripheral blood NK cells.