Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “CD74”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 55 records · Page 3Linked to original sources
PubMed1992

Bauhinia purpurea--a new paraffin section marker for Reed-Sternberg cells of Hodgkin's disease. A comparison with Leu-M1 (CD15), LN2 (CD74), peanut agglutinin, and Ber-H2 (CD30).

Thirty-three cases of Hodgkin's disease (thirteen nodular sclerosis, four diffuse, lymphocyte predominance, and sixteen mixed cellularity) were studied with Bauhinia purpurea (BPA), peanut agglutinin (PNA), anti-Leu-M1, LN2, and Ber-H2 by the avidinbiotin-peroxidase complex (ABC) method in paraffin sections. Reed-Sternberg (RS) cells and variants were stained positively with one or more of the reagents in all cases. BPA staining was positive in 32 of 33 cases (97.0%), PNA staining was positive in 23 of 33 cases (69.7%), Leu-M1 was positive in 13 of 33 cases (39.4%), LN2 was positive in 14 of 33 cases (42.4%), and Ber-H2 was positive in 24 of 33 cases (72.7%). Many RS cells were stained moderately to strongly and were readily recognized in 31 cases (96.9%) of BPA+, 10 (43.5%) of PNA+, 8 (61.5%) of Leu-M1+, 6 (42.9%) of LN2+, and 22 (91.7%) of Ber-H2+ cases; in the remaining positive cases, the RS cells were found only after careful searching. Three staining patterns were recognized: paranuclear, diffuse cytoplasmic, and membranous. These three patterns were obtained with all markers except for LN2. LN2 showed diffuse cytoplasmic staining in most of the positive cells, and a few cells showed paranuclear deposits. BPA reactivity was not affected by formalin fixation or paraffin embedding. Except for RS cells, BPA also showed dense cytoplasmic staining reaction with macrophage-histiocytes. Sixty cases of non-Hodgkin's diffuse lymphomas (30 T- and 30 B-cell origin) were also studied. Tumor cells were not stained with BPA, PNA, and Leu-M1, but stained positively with LN2 in six T-cell lymphomas and thirteen B-cell lymphomas, and with Ber-H2 in six T-cell lymphomas and one B-cell lymphoma. In conclusion, to facilitate the detection of RS cells and related variants in paraffin sections, BPA can be accepted as a useful marker due to its high-detection rate, reproducible staining pattern, and resistance to fixatives.

Antigens, CD↗
PubMed1991

Rapid intracellular pathway gives rise to cell surface expression of the MHC class II-associated invariant chain (CD74).

In previous investigations, it had been shown that class II and associated invariant polypeptides are sorted to an endocytic route where transport is delayed. Invariant chain (Ii) is degraded in a post-Golgi compartment, presumably an endosomal vesicle, and only class II molecules emerge on the cell surface. By using a mAb against the extracytoplasmic domain of human Ii, we demonstrate, by electron microscopy and by cytofluorometry, surface expression of Ii on lymphoma cells and on human B lymphocytes. We examined surface expression of Ii upon inhibition by brefeldin A of intracellular transport from the endoplasmic reticulum to the Golgi stack. This treatment rapidly depletes the cell surface of Ii. In the subsequent absence of brefeldin A, Ii appears rapidly at the cell surface. Within 5 h, the previous level of surface Ii (sIi) is reconstituted. Chloroquine abrogates depletion of sIi by brefeldin A, apparently by inhibition of internalization of sIi. Because on its route to the cell surface Ii is not proteolytically digested, it was possible that Ii and associated class II molecules are not separated on this pathway. Immunochemical studies reveal that on the cell surface of a B lymphoma cell line a proportion of Ii and class II polypeptides are associated.

Antigens, Differentiation, B-Lymphocyte↗
PubMed1997

Biochemical analysis of plasma-soluble invariant chains and their complex formation with soluble HLA-DR.

The invariant chain (CD74) is preferentially localized in the cytoplasm and regulates the loading of exogenous derived peptides into HLA class II heterodimers. In addition, a small proportion of CD74:class II complexes is also expressed on the cell surface. We identified and quantified soluble CD74 (sCD74) molecules in the plasma and sCD74:sHLA-DR complexes by ELISA. EDTA plasma samples from 86 healthy probands were analyzed. sCD74 could be detected in all samples with a mean concentration of 1.14 relative units +/- 1.04 SD (range 0.17-4.31). Approximately 10% of the samples had increased amounts of sCD74 (>3.0 relative units). Complexes of sCD74 and sHLA-DR were detected in all samples and their quantities were positively correlated (r=0.83, p<0.001) with the sCD74 concentrations. SDS-PAGE analysis of plasma samples with high sCD74 concentrations (>3.0 relative units) revealed four isoforms of sCD74 with molecular weights of 45, 43, 35, 31 kDa corresponding to known sizes of intracellular CD74. However, only molecular weights of the 45 and 43 kDa isoforms of sCD74 are found complexed with sHLA-DR. Our data demonstrate, that CD74 molecules are present in their soluble form in the plasma of healthy probands and form complexes with soluble HLA-DR molecules.

Antigens, CD7↗
PubMed1994

Immunoreactivity of neoplastic and non-neoplastic monocytoid B lymphocytes for DBA.44 and other antibodies.

AIMS--To evaluate the immunoreactivities of neoplastic and non-neoplastic monocytoid B cells (MBC) and compare them with hairy cell leukemia (HCL) and mantle cell lymphoma (MCL). METHODS--An immunohistochemical study of paraffin wax embedded sections was done on surgically resected specimens of spleens with MBC clusters from patients with gastric cancer (14 cases), tonsils (five cases), and lymph node (two cases) showing lymphoid follicular hyperplasia (LFH), submandibular lymph nodes containing MBC in Sjögren's syndrome (one case). Extranodal organs affected by MCL (three cases) and monocytoid B cell lymphoma (MBCL) (seven cases), and spleens from HCL (four cases) were also studied. These specimens were fixed in 10% formalin and routinely processed for paraffin wax embedding. Fresh spleen specimens from patients with liver cirrhosis (one case) and gastric cancer (seven cases) were snap frozen. RESULTS--Mantle zone lymphocytes were DBA.44, CD74 positive and showed a weaker reaction for CDw75 than marginal zone lymphocytes and MBC, which were almost DBA negative. In neoplastic diseases tumour cells in MCL were DBA.44, CD74, and CDw75 positive. MBCL showed a positive reaction for CD74 and CDw75, but positivity for DBA.44 was observed in only one of seven cases. The HCL specimens, all positive for DBA.44, showed a weaker reaction for CD74 and a stronger reaction for CDw75 than either MCL and MBCL specimens. CONCLUSION--These results show that mantle zone lymphocytes and MCL more closely matched HCL for reactivity to DBA.44 than MBC and MBCL. Reactivities for DBA.44 and CDw75 were greater in MBCL compared with its non-neoplastic counterpart, MBC.

Adult↗
PubMed2005

Effective therapy of human lymphoma xenografts with a novel recombinant ribonuclease/anti-CD74 humanized IgG4 antibody immunotoxin.

Ranpirnase (Rap) is a cytotoxic ribonuclease (RNase) isolated from frog oocytes. Here we describe high antitumor activity of a novel immunotoxin, 2L-Rap-hLL1-gamma4P, composed of 2 Rap molecules, each fused to the N terminus of the light chain of hLL1, an internalizing anti-CD74 humanized antibody. To reduce unwanted side effects, the constant region of hLL1 was changed from gamma1 to gamma4 and further to gamma4P by replacing serine228 to proline to prevent the formation of a half immunoglobulin G (IgG) common for IgG4. In vitro, 2L-Rap-hLL1-gamma4P retained RNase activity, specific binding to CD74, and was significantly more potent against CD74+ cell lines (Daudi, Raji, and MC/CAR) than naked hLL1. In vivo, the pharmacokinetic profile of 2L-Rap-hLL1-gamma4P was similar to that of naked hLL1. The maximum tolerated dose of 2L-Rap-hLL1-gamma4P in severe combined immunodeficient mice (SCID) or BALB/c mice was 50 microg per mouse. In Raji and Daudi Burkitt lymphoma xenograft models, treatment with a single 5 to 50 microg dose of 2L-Rap-hLL1-gamma4P, given as early or delayed treatment, resulted in cures of most animals. Treatment with 2L-Rap-hLL1-gamma4P was significantly better than all controls, including saline, naked hLL1, and nonspecific immunotoxin. In conclusion, 2L-Rap-hLL1-gamma4P demonstrated excellent in vitro and in vivo efficacy and thus merits further consideration as a therapeutic for CD74+ tumors.

Animals↗
PubMed2005

Constitutive intracellular expression of human leukocyte antigen (HLA)-DO and HLA-DR but not HLA-DM in trophoblast cells.

The nonclassic human leukocyte antigen (HLA)-DM molecules have been proved to positively regulate antigen presentation in classic antigen-presenting cells, whereas in B lymphocytes HLA-DO have been identified as negative regulators of the process. The present report examines whether the negative expression of classic class II molecules in trophoblasts implies negative regulation by HLA-DO. It was revealed by immunofluorescence, confocal microscopy, and subcellular fractionation techniques that human trophoblasts, although not expressing any surface HLA-DR antigens, constitutively express intracellular HLA-DR, HLA-DO, and CD74, but not HLA-DM. Administration of interferon-gamma to the cell culture increased HLA-DR and CD74, induced HLA-DM, but did not alter the expression of HLA-DO and induced HLA-DR release from the cells. These results were confirmed by reverse transcriptase-polymerase chain reaction analysis except that HLA-DM mRNA was detected in control cells, indicating a posttranscriptional regulation. Under the same experimental conditions, human monocytes/macrophages were not expressing intracellular HLA-DO while exhibiting significant levels of HLA-DR, HLA-DM, and CD74. The results presented here reveal for the first time expression of HLA-DO in trophoblasts, which can be of great importance in maintaining the class II-negative state in these cells and consequently protecting the fetus from maternal immune attack.

Animals↗
PubMed2005

Further evidence for increased macrophage migration inhibitory factor expression in prostate cancer.

BACKGROUND: Macrophage migration inhibitory factor (MIF) is a cytokine associated with prostate cancer, based on histologic evidence and circulating (serum) levels. Recent studies from another laboratory failed to document these results. This study's aims were to extend and confirm our previous data, as well as to define possible mechanisms for the discrepant results. Additional aims were to examine MIF expression, as well as the location of MIF's receptor, CD74, in human prostatic adenocarcinoma compared to matched benign prostate. METHODS: MIF amounts were determined in random serum samples remaining following routine PSA screening by ELISA. Native, denaturing and reducing polyacrylamide gels and Western blot analyses determined the MIF form in serum. Prostate tissue arrays were processed for MIF in situ hybridization and immunohistochemistry for MIF and CD74. MIF released into culture medium from normal epithelial, LNCaP and PC-3 cells was detected by Western blot analysis. RESULTS: Median serum MIF amounts were significantly elevated in prostate cancer patients (5.87 +/- 3.91 ng/ml; +/- interquartile range; n = 115) compared with patients with no documented diagnosis of prostate cancer (2.19 +/- 2.65 ng/ml; n = 158). ELISA diluent reagents that included bovine serum albumin (BSA) significantly reduced MIF serum detection (p < 0.01). MIF mRNA was localized to prostatic epithelium in all samples, but cancer showed statistically greater MIF expression. MIF and its receptor (CD74) were localized to prostatic epithelium. Increased secreted MIF was detected in culture medium from prostate cancer cell lines (LNCaP and PC-3). CONCLUSION: Increased serum MIF was associated with prostate cancer. Diluent reagents that included BSA resulted in MIF serum immunoassay interference. In addition, significant amounts of complexed MIF (180 kDa under denaturing conditions by Western blot) found in the serum do not bind to the MIF capture antibody. Increased MIF mRNA expression was observed in prostatic adenocarcinoma compared to benign tissue from matched samples, supporting our earlier finding of increased MIF gene expression in prostate cancer.

Adenocarcinoma↗
PubMed2001

Single-cell cytotoxicity with radiolabeled antibodies.

Previous studies demonstrated the effective, antigen-specific killing of Raji B-lymphoma cells in vitro by radiolabeled anti-CD74, attributable largely to the high level of uptake, of approximately 10(7) antibody (Ab) molecules/cell/ day. This Ab is rapidly delivered to lysosomes for catabolism, so the radionuclide delivered accumulates primarily in lysosomes. In this study, we have tested Abs that bind to the same target cells in similar amounts, but remain primarily on the cell surface, to compare the potency of radioactivity delivered to the cell surface versus the cytoplasm. The Abs tested were anti-major histocompatibility complex class II and anti-CD20. 111In-labeled conjugates made with these two Abs killed cells very effectively and specifically, with 100% kill of sample of 5 x 10(5) cells. Because these Abs remain primarily on the cell surface, it would be predicted that residualizing radiolabels, which are trapped in lysosomes after Ab catabolism, would not be required, and this was observed, i.e., these two Abs were effective when labeled with either 125I or 131I, using conventional iodination, as well as with the residualizing label 111In-labeled DTPA. These results are in contrast to results obtained with anti-CD74, which required a residualizing radiolabel for effectiveness. The uptake of these radionuclides, in cpm/cell, was monitored, and this allowed estimation of the radiation dose delivered; the cytotoxicity observed was consistent with the estimated radiation dose delivered. To establish the generality of the results, we also demonstrated that 111In-labeled anti-CD74 effectively killed three other B-lymphoma cell lines, in addition to Raji and the adherent melanoma cell line SK-MEL-37. By using more potent radionuclides or conjugates of higher specific activity, this approach might be effective with other, lower density antigens.

Antibodies, Monoclonal↗
PubMed2003

A comparison of 4 radionuclides conjugated to antibodies for single-cell kill.

UNLABELLED: We previously found that (67)Ga was more potent and more specific in single-cell kill than other Auger electron emitters and beta-particle emitters, using an anti-CD74 antibody (Ab) (major histocompatibility complex [MHC] class II invariant chain). Because anti-CD74 Abs follow an unusual processing pathway, with rapid delivery in very large amounts to lysosomes, it was important to determine if similar results would be obtained with other, more typical Abs. METHODS: Target cells were Raji B-lymphoma cells, and the Abs tested were antimature MHC class II antigen (lacking the invariant chain) and anti-CD20, both of which react with high-density antigens. Labeling was with (125)I or (131)I, by conventional iodination; with (111)In using the chelator benzyl-diethylenetriaminepentaacetic acid; or with (67)Ga using the chelator 1,4,7-triazacyclononane-1,4,7-triacetic acid. Abs were incubated with the cells for 2 d, uptake of radioactivity was assayed at various times, and toxicity was assayed primarily by a clonogenic assay. The fraction surviving was plotted versus cumulative disintegrations per cell to determine relative potency. RESULTS: The ranking of the radionuclides for potency was (131)I > (67)Ga > (125)I > (111)In. (67)Ga was approximately 2- to 3-fold more potent than (111)In. This was very similar to previous results with anti-CD74. Dosimetry calculations were generally consistent with the level of toxicity observed. In previous studies of nonspecific toxicity, the order of ranking was the same. CONCLUSION: The subcellular location of the bound Ab (whether on the cell surface or the cytoplasm) does not appear to be an important variable in the choice of radionuclide for single-cell kill. (67)Ga is a promising radionuclide for killing micrometastases, for high-density target antigens, but methods for achieving higher specific activity are required to fully exploit this approach. Each of the 4 radionuclides tested has certain advantages, and further studies are required to select the optimal radionuclide for a particular purpose.

Antibodies↗
PubMed2005

Therapy of small subcutaneous B-lymphoma xenografts with antibodies conjugated to radionuclides emitting low-energy electrons.

PURPOSE: Radionuclides emitting low-energy electrons (Auger and conversion electrons of <50 keV) are potentially useful for cancer therapy when conjugated to an antibody, because they can irradiate the cell to which they bind while producing relatively little irradiation of surrounding cells and tissues. We showed previously the ability of such antibody conjugates to treat micrometastatic, disseminated human B-lymphoma in a severe combined immunodeficient mouse model using an anti-CD74 antibody. In this study, we have evaluated the ability of such conjugates to treat s.c. tumors. EXPERIMENTAL DESIGN: Severe combined immunodeficient mice were injected s.c. with Raji, Daudi, or RL B-lymphoma human tumor cells. Antibodies to CD74, CD20, or HLA-DR were radiolabeled with (111)In or (125)I and injected i.v. at various times starting at day 5, and tumor growth was monitored. Controls included the testing of unlabeled antibodies, labeled nonreactive antibodies, and a combination of the two. RESULTS: Therapy of s.c. B-lymphoma was more difficult than therapy of tumor cells that had been injected i.v. Although large, macroscopic tumors were not effectively treated, therapy was effective on s.c. Daudi tumors on day 36 after injection of this slowly growing tumor, with an (111)In anti-CD74 antibody given in two doses. An anti-CD20 antibody labeled with either (111)In or (125)I was able to effectively treat s.c. RL tumors when given as late as day 16 after tumor inoculation. The largest tumors that were effectively treated were macroscopic thin discs (<2 mm in diameter) growing on the mesentery. CONCLUSION: These results extend previous evidence that antibody conjugates with emitters of low-energy electrons can be effective therapeutic agents for micrometastatic cancer.

Animals↗
PubMed1997

Hemopoiesis in human fetal and embryonic liver.

In this review, we describe the topographic distribution of hemopoietic cells of the lymphoid, myeloid, and erythroid lineages in the human fetal and embryonic liver. The data are based on studies of frozen tissue, allowing the determination of a broad range of hemopoietic antigens, and studies on paraffin-embedded tissue, allowing the combination of optimal morphology and immunodetection of lineage-specific antigens. The different hemopoietic lineages each show their own immunophenotype and distribution; intercellular and microenvironmental relationships were easily determined. In a few cases, some scarce CD34-positive early progenitor cells were seen. The number of proliferating cells, identified by monoclonal antibody (MAb) Ki-67, varied from 350 to 2500 (median = 1,500) per square millimeter of tissue. Erythroid cells reacted with antisera to glycophorin A, CDw75, and CD43 and partly surround a central macrophage, whereas the myelomonocytic cells reacted with CD45, CD43, CD74, and antilysozyme serum, and with LN3 from 14 weeks onward. Myelopoietic (CD15 positive) cells were localized mainly around portal triad vessels and increased in number with gestational age. The lymphoid cells showed CD45, CD43, CD45RA/MT2, CD45RA/MB1, MB2, and CD74 reactivity. B cells and their precursors were scattered among the hepatocytes without any sign of focal development in the age range studied. We seldom found cells positive for delta-H chain or C3bR (CD35); C3dR (CD21)-positive cells were even more scarce. Cells reactive with MAb WT1 (CD7) were present in a scattered single pattern (< or = 20/mm2) among the parenchymal cells; cells expressing mature T-cell markers (CD2, CD3, CD5) were rare. Large (> 15 mu) CD43-positive hemopoietic cells in the fetal liver were distinguished that exclusively expressed CD43, probably representing early hemopoietic progenitor cells.

Antigens, CD↗
PubMed2006

Expression and upregulation of cathepsin S and other early molecules required for antigen presentation in activated hepatic stellate cells upon IFN-gamma treatment.

Hepatic stellate cells (HSCs) have been shown to be able to activate T-cells and upregulate expression of surface molecules essential for this process, when treated with IFN-gamma. But little is known about the early molecules expressed by activated hepatic stellate cells under the same treatment. In this study, we investigate the effect of IFN-gamma on the transcription and expression of these early molecules in hepatic stellate cells. We show on the molecular level that activated rat hepatic stellate cells express the class II transactivator, the invariant chain (CD74), the MHC class II molecules, as well as cathepsin S, all of which are known to be responsible for the initial steps of successful antigen presentation. The mRNA and the protein expression level of these molecules is upregulated by IFN-gamma. Importantly, IFN-gamma increases cathepsin S activity, suggesting a possible involvement of this protease in CD74 processing. Our data also show that not only can the HSCs take up antigenic proteins, they can also process them. Our comparative study indicates that the rat HSC-T6 cell line displays sufficient similarity to the activated rat HSCs in order to serve as a model for in vitro studies on the molecular mechanisms of inflammatory response.

Albumins↗
PubMed2006

The temporal profile of genomic responses and protein synthesis in ischemic tolerance of the rat brain induced by repeated hyperbaric oxygen.

Repeated hyperbaric oxygen (HBO) exposure prior to ischemia has been reported to provide neuroprotection against ischemic brain injury. The present study examined the time course of neuroprotection of HBO (3.5 atmosphere absolute, 100% oxygen, 1 h for 5 consecutive days) and the changes of gene/protein expression in rats. First, at 6 h, 12 h, 24 h, and 72 h after HBO sessions, rats were subjected to forebrain ischemia (8 min). Histopathological examination of hippocampal CA1 neurons was done 7 days after ischemia. Second, temporal genomic responses and protein expression were examined at the same time points after HBO sessions without subjecting animals to ischemia. HBO significantly reduced loss of hippocampal CA1 neurons that normally follows transient forebrain ischemia when the last HBO session was 6 h, 12 h, or 24 h before ischemia (survived neurons 55%, 75%, and 53%, respectively), whereas if there was a 72-h delay before the ischemic insult, HBO was not protective (survived neurons only 6%). Statistical analysis on microarray data showed significant upregulation in 60 probe sets including 7 annotated genes (p75NTR, C/EBPdelta, CD74, Edg2, Trip10, Nrp1, and Igf2), whose time course expressions corresponded to HBO-induced neuroprotection. The protein levels of p75NTR, C/EBPdelta, and CD74 were significantly increased (maximum fold changes 2.9, 2.0, and 7.9, respectively). The results suggest that HBO-induced neuroprotection against ischemic injury has time window, protective at 6 h, 12 h and 24 h but not protective at 72 h. Although the precise interaction is to be determined, the genes/proteins relevant to neurotrophin and inflammatory-immune system may be involved in HBO-induced neuroprotection.

Animals↗
PubMed2005

177Lu-antibody conjugates for single-cell kill of B-lymphoma cells in vitro and for therapy of micrometastases in vivo.

Antibodies (Abs) conjugated to 177Lu, a relatively low-energy beta-particle emitter, were evaluated in vitro for their cytotoxic activity and in vivo for their therapeutic activity against disseminated B-cell lymphoma xenografts in SCID mice. 177Lu was compared with other beta-particle emitters ((131)I and 90Y), and also with emitters of low-energy electrons (LEEs, meaning Auger and conversion electrons of < 50 keV). The Abs used reacted with CD20, CD74 or HLA-DR, and the target cell was the Raji B lymphoma. Like the other beta-particle emitters, 177Lu was a potent and specific toxic agent in vitro, when conjugated to Abs recognizing high-density antigens. It appeared to be slightly less potent than (131)I per decay, but this difference was relatively small, and would not be a major factor in the selection of the optimal radionuclide for clinical use. The nonspecific toxicity from 177Lu was less than from 90Y, but 177Lu still produced greater nonspecific toxicity in vitro than LEE emitters. The maximum tolerated dose (MTD) of 177Lu-anti-CD74 in SCID mice was 1.81 MBq (49 microCi)/mouse. When this dose was administered on day 5 after tumor inoculation, significant protection was obtained, but considerably less than the protection obtained in previous experiments with LEE emitters (111)In and 67Ga. In conclusion, 177Lu has advantages over other available beta-particle emitters as a therapeutic agent, but its efficacy in the treatment of micrometastases seems to be less than that of LEE emitters, due to greater nonspecific toxicity. This conclusion, however, may not apply to therapy of macroscopic tumors.

Animals↗
PubMed1999

Specific cutaneous infiltrates in patients with myelogenous leukemia: a clinicopathologic study of 26 patients with assessment of diagnostic criteria.

BACKGROUND: Few recent studies have analyzed the clinicopathologic features of specific cutaneous manifestations of myelogenous leukemia in a large number of patients. OBJECTIVE: We characterize the clinical and histopathologic spectrum of specific cutaneous manifestations in acute (AML) and chronic (CML) myelogenous leukemia, ascertain further diagnostic criteria, and examine current prognosis. METHODS: Thirty-six lesions of specific cutaneous infiltrates from 26 patients with myelogenous leukemia (AML: 17 patients; M:F = 1:2.4; mean age: 52.6 years; AML-French-American-British [FAB] classification subtypes:M1 = 1, M2 = 3, M4 = 8, M5 = 5. CML = 9 patients; M:F = 4.5:1; mean age: 60.6 years) were retrospectively collected for the study. RESULTS: Cutaneous manifestations presented as solitary or multiple reddish to violaceous papules, plaques, and nodules (17 lesions), or as a generalized erythematous maculopapular eruption (9 lesions). Concurrent extramedullary involvement in other peripheral sites (eg, gums, pharynx, orbits) was observed in 10 patients. Histopathologically, lesions revealed nodular/diffuse infiltrates, often with perivascular and periadnexal accentuation, sparing of the upper papillary dermis, and prominent single arraying of neoplastic cells between collagen bundles. Extension to the subcutis was noted in all deep biopsy specimens (26 lesions). Cytomorphologically, medium to large-sized mononuclear cells (myeloblasts and atypical myelocytes) predominated in AML-M1 and M2, whereas M4 and M5 mainly showed small, medium-sized, or large mononuclear cells with slightly eosinophilic cytoplasm and indented, bi-lobular, or kidney-shaped nuclei (atypical monocytoid cells). In CML, either a variable mixture of mature and immature cells of the granulocytic series (myelocytes, metamyelocytes, eosinophilic metamyelocytes, and neutrophils) or a rather monomorphous infiltrate of mononuclear cells were found. Staining for naphthol AS-D chloroacetate-esterase (NASD) was positive in 24 of 36 lesions (66.6%; AML: 16; CML: 8). Immunohistochemical analysis on paraffin sections using a large panel of antibodies (16 lesions: AML: 13; CML: 3) showed strong reactivity for LCA (CD45), lysozyme, myeloperoxidase (MPD), LN2 (CD74), HLA-DR, and MT1 (CD43) in the majority of cases, and variable staining for monocyte/macrophage markers (KP1/CD68, PGM1/CD68, Mac387, Ki-M1p). The neuronal cell adhesion molecule (NCAM) marker CD56 was reactive in 2 cases of CML, but negative in all cases of AML. MIB1(Ki67) stained 20% to 80% of neoplastic cells. CD34, CD15, CD20, and CD3 were negative in all cases. No correlation between histochemical/immunohistochemical features with type of leukemia or FAB-subtype of AML was observed. All patients with CML and AML with adequate follow-up died within 24 months after onset of skin lesions (mean survival, AML: 7.6 months; CML: 9.4 months). CONCLUSION: Specific cutaneous lesions in AML and CML show distinctive clinicopathologic features that allow diagnosis in most cases. Immunohistochemistry on routinely fixed, paraffin-embedded tissue sections provides useful adjunctive information. Simultaneous expression of lysozyme, MPD, CD45, CD43, and CD74 militates in favor of a diagnosis of specific cutaneous infiltrate of myelogenous leukemia. Pitfalls in immunohistologic diagnosis mainly include lack of expression of some myeloid markers (lysozyme, MPD), and aberrant expression of T-cell markers (eg, CD45RO). Regardless of type of myelogenous leukemia, onset of specific skin manifestations correlates with an aggressive course and short survival.

Adult↗
PubMed2006

A distinctive set of genes is upregulated during the inflammation-carcinoma sequence in mouse stomach infected by Helicobacter felis.

Helicobacter pylori infects over half the population worldwide and is a leading cause of chronic gastritis and gastric cancer. However, the mechanism by which this organism induces inflammation and carcinogenesis is not fully understood. In the present study we used insulin-gastrin (INS-GAS) transgenic mice that fully develop gastric adenocarcinoma after infection of H. pylori-related Helicobacter felis. Histological examination revealed that more than half of those mice developed invasive adenocarcinoma after 8 months of infection. These carcinomas were stained by NCC-ST-439 and HECA-452 that recognize 6-sulfated and non-sulfated sialyl Lewis X. Lymphocytic infiltration predominantly to submucosa was observed in most H. felis-infected mice, and this was associated with the formation of peripheral lymph node addressin (PNAd) on high endothelial venule (HEV)-like vessels detected by MECA-79. Time-course analysis of gene expression by using gene microarray revealed upregulation of several inflammation-associated genes including chemokines, adhesion molecules, surfactant protein D (SP-D), and CD74 in the infected stomach. Immunohistochemical analysis demonstrated that SP-D is expressed in hyperplasia and adenocarcinoma whereas CD74 is expressed in adenocarcinoma in situ and invasive carcinoma. These results as a whole indicate that H. felis induces HEV-like vessels and inflammation-associated chemokines and chemokine receptors, followed by adenocarcinoma formation.

Adenocarcinoma↗
PubMed2025

Computational network biology analysis revealed COVID-19 severity markers: Molecular interplay between HLA-II with CIITA.

COVID-19, severe acute respiratory syndrome coronavirus 2, rapidly spread worldwide. Severe and critical patients are expected to rapidly deteriorate. Although several studies have attempted to uncover the mechanisms underlying COVID-19 severity, most have focused on the perturbations of single genes. However, the complex mechanism of COVID-19 involves numerous perturbed genes in a molecular network rather than a single abnormal gene. Thus, we aimed to identify COVID-19 severity-specific markers in the Japanese population using gene network analysis. In order to reveal the severity-specific molecular interplays, we developed a novel computational network biology strategy that measures dissimilarity between networks based on the comprehensive information of gene network (i.e., expression levels of genes and network structure) by using Kullback-Leibler divergence. Monte Carlo simulations demonstrated the effectiveness of our strategy for differential gene network analysis. We applied this method to publicly available whole blood RNA-seq data from the Japan coronavirus disease 2019 Task Force and identified differentially regulated molecular interplays between 368 severe and 105 non-severe samples. Our analysis suggests the gene network between HLA class II, CIITA, and CD74 as a COVID-19 severity specific molecular marker. Although the association between HLA class II and COVID-19 has been demonstrated, our data analysis revealed that the molecular interplay of HLA class II with its target and/or regulator is a crucial marker for COVID-19 severity. Our findings from computational network biology analysis suggest that suppression and activation of the molecular interplay between HLA class II, CIITA, and CD74 provide crucial clues to uncover the mechanisms of COVID-19 severity.

Humans↗
PubMed2004

Differentially expressed genes in pancreatic ductal adenocarcinomas identified through serial analysis of gene expression.

Serial analysis of gene expression (SAGE) is a powerful tool for the discovery of novel tumor markers. The publicly available online SAGE libraries of normal and neoplastic tissues (http://www.ncbi.nlm.nih.gov/SAGE/) have recently been expanded; in addition, a more complete annotation of the human genome and better biocomputational techniques have substantially improved the assignment of differentially expressed SAGE "tags" to human genes. These improvements have provided us with an opportunity to re-evaluate global gene expression in pancreatic cancer using existing SAGE libraries. SAGE libraries generated from six pancreatic cancers were compared to SAGE libraries generated from 11 non-neoplastic tissues. Compared to normal tissue libraries, we identified 453 SAGE tags as differentially expressed in pancreatic cancer, including 395 that mapped to known genes and 58 "uncharacterized" tags. Of the 395 SAGE tags assigned to known genes, 223 were overexpressed in pancreatic cancer, and 172 were underexpressed. In order to map the 58 uncharacterized differentially expressed SAGE tags to genes, we used a newly developed resource called TAGmapper (http://tagmapper.ibioinformatics.org), to identify 16 additional differentially expressed genes. The differential expression of seven genes, involved in multiple cellular processes such as signal transduction (MIC-1), differentiation (DMBT1 and Neugrin), immune response (CD74), inflammation (CXCL2), cell cycle (CEB1) and enzymatic activity (Kallikrein 6), was confirmed by either immunohistochemical labeling of tissue microarrays (Kallikrein 6, CD74 and DMBT1) or by RT-PCR (CEB1, Neugrin, MIC1 and CXCL2). Of note, Neugrin was one of the genes whose previously uncharacterized SAGE tag was correctly assigned using TAGmapper, validating the utility of this program. Novel differentially expressed genes in a cancer type can be identified by revisiting updated and expanded SAGE databases. TAGmapper should prove to be a powerful tool for the discovery of novel tumor markers through assignment of uncharacterized SAGE tags.

Adenocarcinoma↗