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At least 73 records · Page 4Linked to original sources

Diffuse large-cell lymphoma of B-cell origin and deficient T-cell function in a patient with rheumatoid arthritis.

An increased incidence of non-Hodgkin's lymphoma has been described in patients with rheumatoid arthritis. Mechanisms related to abnormal immune regulation have been postulated, but no patients with rheumatoid arthritis and lymphoma have been previously well characterized immunologically. We describe here a patient with long-standing rheumatoid arthritis in whom a B-cell diffuse large-cell lymphoma developed. He was found to have a severe T-cell immunodeficiency and evidence of persistent Epstein-Barr virus infection. Epstein-Barr nuclear antigen was not found to be present within lymphoma cells. The combination of defective T-cell function and persistent Epstein-Barr virus infection may have predisposed this patient with rheumatoid arthritis to the development of a malignant clone of B lymphocytes.

Arthritis, Rheumatoid↗

In young primary cultures of rabbit kidney cortical collecting ducts intercalated cells originate from principal or undifferentiated cells.

The evolution of a primary culture of rabbit kidney cortical collecting tubule was followed over a period of 10 to 11 days. The cell types of this segment were characterized by using monoclonal antibodies, specifically directed against principal (Mab 703) and intercalated (Mab 503) cells of the apical membrane. The activity of a H+ pump ATPase was revealed in Mab 503-labeled cells, confirming that these cultured cells present characteristics of intercalated cells. The primary culture was also stained with peanut agglutinin (PNA), a specific ligand of beta intercalated cells. During the first two days, some cells, mainly Mab 503-labeled cells, disappeared, and cell division did not occur. At 2 days, the culture showed 80% and 18% of Mab 703-labeled and Mab 503-labeled cells, respectively. The first mitoses were observed at 2 days. From two to four days, cell division was nestly in Mab 703-labeled cells and only rarely seen in Mab 503-labeled cells, although during this period the proportion of Mab 703-labeled cells decreased to 44% of cells and that of Mab 503-labeled cells increased to 30%. The labeling with PNA was curious. Up to 2 days, PNA stained Mab 503-labeled cells, but from 4 days it stained other cells, probably dedifferentiated ones. In our culture conditions types of cells other than Mab 703-labeled and Mab 503-labeled cells occurred. First, throughout the life of the culture, some cells were not recognized by any monoclonal antibody; their number varied between 10 and 28% of the total cell number.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Mutational analysis of IgVH and BCL-6 genes suggests thymic B-cells origin of mediastinal (thymic) B-cell lymphoma.

Mediastinal (thymic) large B-cell lymphoma (MBL) has been defined as a subtype of diffuse large B-cell lymphoma (DLBL) arising in the mediastinum with characteristic clinicopathological features. It has been postulated that MBL arise from non-circulating thymic B-cells and represent a distinct lymphoma entity, however, the histogenesis of the disease is not yet fully understood. In order to clarify the histogenetic derivation of MBL and to determine the relationship of MBL to thymic B-cells we have analyzed the nucleic acid sequences of immunoglobulin (Ig) heavy chain variable region (VH) and 5' noncoding region of BCL-6 genes in normal thymic B-cells and six cases of MBL. Thymic B-cells and tumor cells of MBLs displayed hypermutated VH and/or BCL-6 genes but intraclonal divergence did not associate with these mutations. Since somatic mutations of the IgVH and BCL-6 genes are histogenetic markers of B-cell transit through the germinal centre (GC), these results suggest that both thymic B-cells and MBLs derived from GC or an equivalent environment where B-cells underwent somatic hypermutation. The similar pattern of mutations of IgVH and BCL-6 genes found in thymic B-cells and MBLs further supports the theory that MBLs originate from thymic B-cells.

Adult↗

Cloning and expression of a novel MAPKK-like protein kinase, lymphokine-activated killer T-cell-originated protein kinase, specifically expressed in the testis and activated lymphoid cells.

A novel protein kinase, TOPK (T-LAK cell-originated protein kinase), was isolated from a lymphokine-activated killer T (T-LAK) cell subtraction cDNA fragment library. The open reading frame of the TOPK gene encodes a protein of 322 amino acids, possessing a protein kinase domain profile. The cap site analysis of the 5'-end of TOPK mRNA revealed two forms, a major full-length form and a minor spliced form at the 5'-site, both encoding the same protein. A BLAST homology search and phylogenetic analysis indicated that TOPK is related to dual specific mitogen-activated protein kinase kinase (MAPKK). The transfection of the TOPK gene to COS-7 cells up-regulated a phosphorylation of p38 MAPK but not ERK1/2 or SAPK/JNK. Gel precipitation study indicated that TOPK protein can be associated with p38 in vitro. Tissue distribution of TOPK mRNA expression was specific for the testis, T-LAK cells, activated lymphoid cells, and lymphoid tumors. On the other hand, deactivated T-LAK cells did not show TOPK mRNA expression. These data suggest that TOPK is a newly identified member of a novel MEK3/6-related MAPKK that may be enrolled in the activation of lymphoid cells and support testicular functions.

Amino Acid Sequence↗

Autoantibody-associated cross-reactive idiotypes expressed at high frequency in chronic lymphocytic leukemia relative to B-cell lymphomas of follicular center cell origin.

Using murine monoclonal antibodies (MoAbs) specific for immunoglobulin (Ig) cross-reactive idiotypes (CRI), we performed immunohistochemical analyses on frozen tissue sections and cytocentrifuge preparations of Ig-expressing malignant cells from patients with chronic lymphocytic leukemia (CLL) and B-cell non-Hodgkin's lymphomas (NHL) of follicular center cell origin. Twenty percent (4/20) of the Ig kappa light chain-expressing CLL cells reacted with 17.109, a MoAb against a major CRI on human IgM autoantibodies that is encoded by a conserved Ig variable-region gene (V gene) of the V kappa IIIb sub-subgroup. Another MoAb specific for V kappa IIIb framework determinant(s) reacted exclusively with all the 17.109-reactive CLL cells. Only one of 20 kappa light-chain-expressing CLL cells reacted with 6B6.6, a monoclonal antibody specific for a CRI commonly found on rheumatoid factor (RF) paraproteins with light-chain variable regions of the V kappa IIIa sub-subgroup. Finally, greater than 20% (8/34) of all CLL reacted with G6, a MoAb specific for an Ig heavy chain-associated CRI present on several RF paraproteins. In contrast, these CRIs were expressed at significantly lower frequencies in NHL of follicular center cell origin. Only one of 30 NHL expressing kappa light chains reacted with the 17.109 MoAb. Also, in contrast to the concordance between the 17.109-CRI and V kappa IIIb framework determinant(s) in CLL, two lymphomas in addition to the 17.109-reactive lymphoma were recognized by the anti-V kappa IIIb framework MoAb. None of the NHL reacted with either the 6B6.6 or the G6 MoAbs. These results are the first to demonstrate that CLL and NHL differ with respect to the expression of autoantibody-associated CRIs. The data support the notion that NHL of follicular center cell origin differs from CLL in its utilization and/or somatic mutation of Ig variable-region genes. The physiological and immunotherapeutic implications of these findings are discussed.

Autoantibodies↗

[The role of cells originating from seminal vesicles in aspiration biopsy smears of the prostate (author's transl)].

328 (30.7%) of 1068 prostatic aspirates obtained from 874 patients contained cells of seminal vesicle origin. Cells originating from the seminal vesicles were recognized in aspirates obtained from 27.6% of the untreated patients and in aspirates from 60.4% of the treated patients. Patients of the latter group had received hormonal treatment or radation therapy, or both, or had been surgically treated by prostatectomy. The occurrence of cells derived from seminal vesicles was due to the site of the needled prostatic lesion in 21% of the aspirates obtained, to treatment in 21% and to incorrect biopsy technique in the remaining 58%. A false cytologic report was made in the case of 6 aspirates (1.6%).

Biopsy, Needle↗

Distribution of complement receptor subtypes in non-Hodgkin's lymphomas of B-cell origin.

Surface receptors specific for either the C4b (CR1) or C3d (CR2) component of complement were examined on the neoplastic cells from 30 cases of non-Hodgkin's lymphoma of B-cell origin and on cells derived from 9 normal lymphoid tissues. Lymphocyte suspensions from non-neoplastic peripheral blood, tonsils, and lymph node contained three categories of complement receptor lymphocytes (CRL): cells with receptors for both C4b and C3d (CR1+, CR2+); cells with receptors for C4b but not C3d (CR1+, CR2-), and cells with receptors for C3d but not C4b (CR1-, CR2+). The mean of the proportion of total CRL expressing receptors only of C3d (CR1-, CR2+) was 0.35 for non-neoplastic tissues and 0.28 for malignant lymphomas of follicular center cell (FCC) origin. However, the proportion of cells with this phenotype was significantly higher in well differentiated lymphocytic lymphomas (WDL) and chronic lymphocytic leukemia (CLL) (0.65) and in intermediately differentiated lymphocytic lymphomas (IDL) (0.59). Histologic compartmentalization of the CRL subtypes was observed in frozen sections of normal lymphoid tissue. CR1+ cells were present in lymphoid follicles interfollicular areas, and in splenic red pulp. CR2+ cells were confined to lymphoid follicles. These findings strongly suggest that complement receptor phenotypes may be useful markers of B-cell differentiation.

B-Lymphocytes↗

The follicle-associated epithelium in the bursa of Fabricius cell origin studied by means of quail-chick chimeras and monoclonal antibodies.

The cell origin of the follicle-associated epithelium (FAE) of the bursa of Fabricius was studied by two different technical approaches. Precolonized quail bursal rudiments were grafted into chick embryos and the grafts were recovered 2 wk after hatching of the recipients. By taking advantage of the distinct nuclear characteristics of chick and quail cells, it could be shown that the specialized FAE consists of a mixture of epithelial cells, with special features, among which hemopoietic cells, originating from the host, are dispersed. Staining of chicken bursas with different monoclonal antibodies reacting either with the epithelial component (BEP-1) or with the hemopoietic cells of the bursa (L22, L17) confirmed that hemopoietic cells, presumably macrophages, are mixed with the epithelial cells at the level of FAE.

Animals↗

Variation of peptide transporter (PepT1 and HPT1) expression in Caco-2 cells as a function of cell origin.

Caco-2 cell cultures are a widely used in vitro model for the small intestinal drug transport, although large differences have been reported for actively transported substrates from different laboratories. Therefore, we compared three different Caco-2 clones: (1) from the American Culture Tissue Collection (ATCC), (2) from the German Cancer Research Center (DKFZ) in Heidelberg, and (3) from the University Hospital in Marburg in different passage numbers regarding their morphology, multilayers, and tight junction formation, as well as expression of the peptide transporters, HPT1 and PepT1. We determined tight junction formation by measurement of the transepithelial electrical resistance, multilayer formation by confocal laser scanning microscopy, the expression of PepT1 and HPT1 by RT-PCR, indirect immunofluorescence and the permeability of the PepT1 substrate, cephradine. Morphology and TEER-values varied strongly between the different clones. The expression of PepT1 and HPT1 increased in the following order: HD > ATCC > MR. Indirect immunofluorescence revealed a heterogeneous distribution of the transporters in ATCC-cells, whereas it was homogeneous in HD-cells. Only a very weak expression was found in MR-cells. While in ATCC-cells expression of transporters decreased with increasing passage number, it increased in HD-cells. Expression levels were congruent with the transport of cephradine. Expression of PepT1 and HPT1 was strongly affected by the culture conditions. Under identical culture conditions, Heidelberg (HD) Caco-2 cells seemed to be an appropriate in vitro cell culture model for the transport of actively transported drugs, because interpassage changes are low and the transporter distribution was homogeneous throughout the monolayer.

Caco-2 Cells↗

Porcine lymphoblastoid cell lines of B-cell origin.

Two lymphoblastoid cell lines were isolated from different pigs and were maintained in culture for over 100 passages or 20 months. These cell lines were characterized by their cell surface antigens, ability to stimulate a mixed lymphocyte reaction and production of immunoglobulin. When tested against a panel of monoclonal anti-cell surface antigen antibodies, only those monoclonal antibodies which detect porcine class I or II molecules reacted against the lymphoblastoid cell lines in a microcytotoxicity assay. The two pig cell lines could stimulate peripheral blood mononuclear cells in a mixed lymphocyte reaction. P-SC(1) and P-16(2) also demonstrated a dependency upon the presence of 2-mercaptoethanol for cell division. The secretion of pig immunoglobulin by P-SC(1) or P-16(2) was first demonstrated by ELISA using a polyclonal anti-swine IgG (heavy and light chain) serum. By the use of monoclonal anti-IgA, IgG or IgM antibodies in an enzyme-linked assay on Western blots of P-SC(1) or P-16(2) lysate/supernatant, the two cell lines were demonstrated to be producing a whole monomeric IgA molecule and a mu chain.

Animals↗

Primary mesenchymal or mixed-cell-origin lung tumors in four dogs.

Primary lung tumors of mesenchymal or mixed cell origin were diagnosed in 4 dogs with clinical and radiographic abnormalities indicating an intrathoracic mass. Each dog had 1 large intrapulmonary lesion, and 1 dog also had nodules scattered throughout all lung lobes. Two dogs were euthanatized; 1 had a biphasic pulmonary blastoma; and the other had a pulmonary chondroblastic osteosarcoma with intrapulmonary metastases. The masses in the other 2 dogs were hamartomas (lipomatous in 1, microcystic in the other), which were resected. Both dogs survived more than 1 year after surgery. Primary lung tumors are uncommon in dogs and are generally malignant (adenocarcinomas or carcinomas). Tumors of connective tissue or mixed cell origin are rare, but the outcome is potentially good after surgical removal.

Animals↗

Human embryonic stem cells: origin, properties and applications.

Human embryonic stem cells originate from the human preimplantation embryo. The derivation of the first human embryonic stem cells was reported in 1998. Since then we have learnt a great deal about how to isolate and culture these cells. Additionally, their stem cell phenotype and differentiation competence have been determined. Although it is expected that many basic biological properties, such as self-renewal and cell specification, are evolutionary conserved, at least from the mouse, we lack significant knowledge about the molecular events that regulate the unique stem cell features of human embryonic stem cells. The pluripotent nature of human embryonic stem cells has attracted great interest in using them as a source of cells and tissues in cell therapy. Recent progress in human somatic cell nuclear transfer suggests that there may be a solution to the immunotolerance problems associated with the use of human embryonic stem cells in cell-replacement therapy. Thus, human embryonic stem cells supply the research community with unique research tools to study basic biological processes in human cells, model human genetic diseases and develop new cell-replacement therapies.

Animals↗

Cell origin and paracrine control of interstitial collagenase in the guinea pig uterine cervix--evidence for a low molecular weight epithelial cell-derived collagenase stimulator.

Dilatation of the uterine cervix at parturition is achieved by degradation of type I collagen, the main structural protein in the cervix, by interstitial collagenase. In order to determine the cell origin of interstitial collagenase in the cervix, separate stromal and epithelial cell cultures were established. Using a highly sensitive and specific assay for collagenase that utilizes [3H]telopeptide-free type I collagen as a substrate, we determined that the cells of origin of collagenase were cervical stromal cells and not cervical epithelial cells. Cells of cervical epithelium produced factors in culture that stimulated stromal cell collagenase production. The addition of epithelial cells or epithelial cell-conditioned culture medium to stromal cells resulted in a dose-dependent stimulation of stromal cell collagenase production with a maximum increase of 3- or 6-fold, respectively. To characterize the collagenase-stimulatory activity produced by epithelial cells, epithelial cell-conditioned culture medium was extracted under conditions that optimized the recovery of peptides and was subjected to ion-exchange batch extraction as well as reverse-phase and size-exclusion HPLC. Collagenase-stimulatory activities were mainly recovered in neutral extracts of epithelial cell-conditioned medium with an apparent molecular mass of 6 kDa. In conclusion, interstitial collagenase is produced by cervical stromal cells and not by cervical epithelial cells. Epithelial cells, however, secrete factors of low molecular size that stimulate stromal cell collagenase production.

Animals↗

Primary gastric lymphoma of T-cell origin: clinicopathologic features and treatment outcome.

We conducted a retrospective analysis to investigate the natural history and the clinical outcome after treatment of primary gastric lymphoma of T-cell origin. Seventeen cases of T-cell origin among 444 primary gastric lymphoma patients were analyzed. The median age of the 14 male and 3 female patients was 49 years (range 22-76 years). The median progression-free survival (PFS) and overall survival (OS) were only 10 months (95% CI; 0-20 months), and 12 months (95% CI; 4-21 months), respectively. This study showed that the incidence of this subtype of T-cell gastric lymphoma was very rare, and had poor prognosis.

Adult↗

Lymphokine-activated killer T-cell-originated protein kinase phosphorylation of histone H2AX prevents arsenite-induced apoptosis in RPMI7951 melanoma cells.

PURPOSE: Arsenic is a valuable therapeutic tool in cancer treatment. Lymphokine-activated killer T-cell-originated protein kinase (TOPK) is highly expressed in cancer cells, but its specific function is still unknown. We investigated the role of TOPK in arsenic-induced apoptosis in RPMI7951 human melanoma cells. EXPERIMENTAL DESIGN: Expression of TOPK was evaluated in different melanoma cell lines, and liquid chromatography-tandem mass spectrometry analysis was used to identify proteins binding with TOPK. Immunofluorescence, Western blot, and flow cytometry were used to assess the effect of arsenic on TOPK, histone H2AX, and apoptosis in RPMI7951 cells. RESULTS: Melanoma cell lines expressing high levels of TOPK were more resistant to arsenite (As(3+))-induced apoptosis. As(3+) treatment induced phosphorylation of TOPK and histone H2AX in RPMI7951 human melanoma cells. Liquid chromatography-tandem mass spectrometry results indicated that TOPK could bind with histone H2AX, and in vitro and in vivo assays confirmed that TOPK binds with and phosphorylates histone H2AX. As(3+) treatment caused phosphorylation of TOPK, which colocalized with phosphorylated histone H2AX in the nucleus. TOPK small interfering RNA cells exhibited a decreased phosphorylation of histone H2AX with As(3+) treatment. As(3+)-induced apoptosis was decreased in H2AX(-/-) cells but increased in TOPK small interfering RNA cells. CONCLUSIONS: TOPK binds with histone H2AX and inhibits As(3+)-induced apoptosis through phosphorylation of histone H2AX. Melanoma cell lines with high levels of TOPK are more resistant to As(3+)-induced apoptosis. Therefore, inhibition of TOPK activity combined with As(3+) treatment may be helpful in the treatment of melanomas.

Animals↗

Evidence regarding a stem cell origin of hepatocellular carcinoma.

The cellular origin of tumors remains as one of the unanswered, fundamental questions of cancer biology. The notion that tumors may arise from tissue stem cells is supported by phenotypic similarities between these two cell types, such as proliferative potential and expression of onco-fetal proteins. Liver stem cells, or oval cells, have been put forth as a possible target for hepatocarcinogens. Genetically modified and in vitro transformed oval cells have been shown to form tumors in transplantation to animals. Chemical carcinogenesis models in the liver demonstrate varying degrees of oval cell proliferation. There is also preliminary evidence that hepatocellular carcinoma may maintain a bipotential phenotype consistent with an oval cell origin. Whereas definitive proof of an oval cell origin of hepatocellular has yet to be presented, the current circumstantial evidence justifies continued research on this subject.

Animals↗

Induction of unusual pancreatic neoplasms, with morphologic similarity to human tumors, and evidence for their ductal/ductular cell origin.

A variety of pancreatic neoplasms, including giant cell, poorly differentiated or other unusual types, some morphologically similar to those observed in humans were induced in Syrian hamsters. Unclassified or anaplastic forms were also noted in the hamster. The finding of a blood group A-like antigen, which is produced by normal pancreatic ductal and ductular cells, in all of these induced tumors, but none in acinar, insular, and mesenchymal cells, suggests their ductal/ductular cell origin.

ABO Blood-Group System↗

Test for fused-cell origin of tumors with Mus caroli carrying glucose-6-phosphate dehydrogenase cellular mosaicism.

A test system for examining the fused cell-origin of tumors was developed by application of Mus caroli carrying the X-chromosome inactivation cellular mosaicism for G6PD. A G6PD heterodimer pattern is expected if a tumor is initiated from a fused cell. Among tumors induced by subcutaneous injection of a high dose of MCA, three tumors exhibited a single G6PD phenotype and one tumor exhibited a multiple G6PD phenotype; however, the G6PD heterodimer pattern was not found. Although the results obtained were not conclusive, this system is thought to be useful for detecting a possible fused cell-origin of tumors.

Animals↗