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At least 253 records · Page 14Linked to original sources

Malignant lymphomas of follicular center cell origin in humans. V. Incidence, clinical features, and prognostic implications of transformation of small cleaved cell nodular lymphoma.

Seventy-five cases of small cleaved cell nodular lymphoma (SCC-N) were reviewed. Thirty-four cases underwent repeat biopsy a median of 54 months after diagnosis (range, 7-116 months) because of progressive or recurrent disease. Histologic conversion to a transformed (noncleaved) cell lymphoma was found at re-biopsy in 13 of 34 cases (38%). Neither age, gender, stage, visceral sites of disease, nor symptoms at presentation were predictive of subsequent conversion. Similarly, none of the clinical features analyzed at the time of rebiopsy were predictive of whether the rebiopsy would show stable histology or transformation. Documentation of transformation was of significant prognostic value. Although rebiopsies were performed at the time of progressive disease, survival following re-biopsy was 37.5 months for patients found to have cleaved cell lymphoma at re-biopsy, and only 2.5 months for those with transformed cell lymphoma at re-biopsy. Two of the cases which had immunoglobulin surface markers studied at diagnosis and at transformation, showed retention of heavy and light chain markers. This implies that the change in appearance involves the original neoplastic clone and was not due to a second neoplasm. Development of transformed cell lymphoma is one of the most common features of the aggressive phase of indolent lymphoma. Repeat biopsy in all patients with indolent lymphoma who have relapsing or progressive disease is recommended.

Adult↗

Comparative studies of human malignant mesothelioma in vivo, in xenografts in nude mice, and in vitro. Cell origin of malignant mesothelioma.

Several decades ago, it was reported that normal and malignant mesothelial cells were transformed into distinct cell types (epithelial to fibrous and fibrous to epithelial) when transferred to in vitro conditions. Those tissue culture data are still cited as evidence supporting that the mesothelial cell has multipotentiality of differentiation and the mesothelial cell is a sole precursor of malignant mesothelioma cells. Six cell lines of heterotransplanted human malignant mesothelioma in nude mice and one cell line of subcultured human malignant mesothelioma in vitro have been established. To establish the validity of the classic concept of multipotentiality of malignant mesothelioma, we studied malignant mesothelioma cells of the seven cases using in vivo cultures, xenografts in nude mice and an in vitro tissue culture, utilizing histology, histochemistry, immunocytochemistry and electron microscopy. The nature of the original malignant mesothelioma cells was clearly shown to be well preserved in both the heterotransplanted and subcultured cells. Data did not support earlier hypotheses that mesothelial cells are capable of differentiating into distinct cell lines. The mesothelial cell and the submesothelial connective tissue cells are the precursors of the neoplastic cells in malignant mesothelioma.

Aged↗

Common clonal T-cell origin in a patient with T-prolymphocytic leukaemia and associated cutaneous T-cell lymphomas.

An unusual course was observed in a patient with indolent T-prolymphocytic leukaemia (T-PLL) who subsequently developed mycosis fungoides (Mf), lymphomatoid papulosis (LyP) and cutaneous CD30+ anaplastic large cell lymphoma (ALCL). Polymerase chain reaction analysis demonstrated identical monoclonal T-cell receptor-beta and -gamma gene rearrangements in all the different clinical entities. Furthermore, cytogenetic studies revealed the same aberrant clone with trisomy of chromosome 8 in T-PLL and ALCL cells. This unique observation suggests that in T-PLL, the leukaemic cells might undergo secondary transformation, subsequently resulting in different phenotypes of cutaneous T-cell lymphoma.

Aged↗

Expression of hepatitis B virus genes in early embryonic cells originated from hamster ova and human spermatozoa transfected with the complete viral genome.

AIM: To detect the expression of hepatitis B virus (HBV) genes (HB S and C genes) in early embryonic cells after introducing motile human sperm carrying HBV DNA into zona-free hamster oocytes via the in vitro fertilization (IVF) technique. METHODS: Human sperm-mediated HBV genes were delivered into zona-free hamster oocytes by the IVF method. Polymerase chain reaction (PCR) was used to detect HB S and pre-Core/Core (pre-C/C) coding genes both in one- and two-cell embryos. Reverse transcription-PCR (RT-PCR) analysis was used to study the expression of the two genes. Fluorescence in situ hybridization (FISH) analysis using the full-length HBV DNA as the hybridization probe was performed to confirm the integration of viral DNA in the host embryonic genome. RESULTS: Both HB S and pre-C/C coding genes are present and transcribed in one- and two-cell embryos originated from hamster ova IVF with human spermatozoa carrying HBV DNA sequences. CONCLUSION: Sperm-mediated HBV genes are able to replicate and express themselves in early embryonic cells. These results provide direct evidence that HBV DNA could transmit vertically to the next generation via the male germ line.

Animals↗

Stem and progenitor cells: origins, phenotypes, lineage commitments, and transdifferentiations.

Multipotent stem cells are clonal cells that self-renew as well as differentiate to regenerate adult tissues. Whereas stem cells and their fates are known by unique genetic marker studies, the fate and function of these cells are best studied by their prospective isolation. This review is about the properties of various highly purified tissue-specific multipotent stem cells and purified oligolineage progenitors. We contend that unless the stem or progenitor cells in question have been purified to near homogeneity, one cannot know whether their generation of expected (or unexpected) progeny is a property of a known cell type. It is interesting that in the hematopoietic system the only long-term self-renewing cells in the stem and progenitors pool are the hematopoietic stem cells. This fact is discussed in the context of normal and leukemic hematopoiesis.

Animals↗

Adventitia-derived nitric oxide in rat aortas exposed to endotoxin: cell origin and functional consequences.

The role of adventitial cells in bacterial lipopolysaccharide (LPS)-induced vascular nitric oxide (NO) overproduction has been largely ignored. In rat aortas exposed to LPS in vitro or in vivo, it was found that adventitia contained the major part of NO synthase (NOS)-2 protein (Western blot and immunohistochemistry) and generated the largest amount of NO (electron paramagnetic resonance spin trapping). NOS-2 immunoreactive cells were mainly resident macrophages at an early stage (5 h, in vitro or in vivo) and fibroblasts at a later stage (20 h, in vitro). Adventitial NOS-2 activity largely accounted for 1) the relaxing effect of L-arginine in rings exposed to LPS in vivo, 2) generation of an "NO store" revealed by N-acetylcysteine-induced relaxation, and 3) formation of protein-bound dinitrosyl iron complexes in the medial layer of aortic rings exposed to LPS in vitro. In conclusion, the adventitia is a powerful source of NO triggered by LPS in the rat aorta. This novel source of NO has an important impact on smooth muscle function and might be implicated in various inflammatory diseases.

Animals↗

[Dendritic cells originated from the peripheral blood in chronic hepatitis B patients can induce specific T cell immune response].

OBJECTIVE: To study whether dendritic cells (DCs) derived from the peripheral blood in chronic hepatitis B patients can induce specific T cell immune response. METHODS: (1)The subjects were divided into 3 groups: chronic hepatitis B group (CHB), acute hepatitis B group (AHB), and normal donor group (ND). The peripheral blood mononuclear cells (PBMCs) isolated from those subjects were stimulated with HBcAg 18 to 27 CTL epitope peptide, and intracellular cytokine staining (ICCS) was used for detecting IFN-gamma, IL-2 and TNF-alpha produced by CD8+ T cell. (2) DCs generated from PBMCs were pulsed with HBcAg 18 to 27 CTL epitope peptide, then were cocultured with autologous lymphocytes for 10 days to induce antigen-specific T cell, which was assessed by ICCS and cytotoxic assay. RESULTS: (1) The memory effect of the PBMCs from AHB group to HBcAg 18 to 27 CTL epitope peptide was stronger than that from CHB or ND group (t=2.508-3.305, P<0.05). (2)After lymphocytes were cocultured with DC treated with HBcAg 18 to 27 CTL epitope peptide, antigen-specific T cell effect was induced. And the killing rates were (57.0+/-23.0)%, (49.5+/-20.2)%, (21.8+/-12.9)% at the effector/target of 30:1, 10:1, 3:1, which were higher than that in control group. CONCLUSIONS: The memory T cells against HBV antigen lacks in CHB patients. DCs from CHB patients pulsed with HBcAg 18 to 27 epitope peptide can induce HBV antigen-specific T cell, which can kill specific target cells and produce cytokines involved in virus clearance.

Adult↗

Hepatosplenic T-cell lymphoma: a distinct clinicopathologic entity of cytotoxic gamma delta T-cell origin.

We identified eight cases of T-cell lymphoma with evidence of a gamma delta phenotype over a 13-year period. Seven of these cases conformed to a distinct clinicopathologic entity of hepatosplenic gamma delta T-cell lymphoma. Nearly all of these patients were young adult males (five of seven), with a median age at presentation of 20 years. They presented with marked hepatosplenomegaly, without lymphadenopathy or significant peripheral blood lymphocytosis. Thrombocytopenia was seen in all patients, and five of seven were mildly anemic. The clinical course was aggressive, and despite multiagent chemotherapy, the median survival duration was less than 1 year. The morphologic findings were uniform; a monomorphic population of medium-sized lymphoid cells with moderately clumped chromatin and a rim of pale cytoplasm infiltrated the sinusoids of the spleen, liver, and bone marrow. The cells had a characteristic immunophenotype: CD2+, CD3+, CD4-, CD5-, CD7+, CD16+, CD57-, CD25-, T-cell receptor (TCR)delta +, beta F1-. CD8 was positive in four of seven cases tested, and CD56 was positive in five of six. All cases expressed the cytotoxic granule-associated protein, TIA1, but perforin was detected in only one case. All cases with assessable DNA had a TCR gamma gene rearrangement, and lacked Epstein-Barr virus sequences. Isochromosome 7q was identified in two cases with cytogenetic information. The one case of cutaneous gamma delta T-cell lymphoma differed in its clinical manifestations, histologic appearance, and immunophenotype. We conclude that hepatosplenic gamma delta T-cell lymphoma is a distinct clinicopathologic entity derived from cytotoxic gamma delta T cells, and should be distinguished from other lymphomas of T-cell and natural-killer cell (NK)-like T-cell derivation.

Adolescent↗

The expression of the homeobox gene Msx1 reveals two populations of dermal progenitor cells originating from the somites.

Experimental manipulation in birds has shown that trunk dermis has a double origin: dorsally, it derives from the somite dermomyotome, while ventrally, it is formed by the somatopleure. Taking advantage of an nlacZ reporter gene integrated into the mouse Msx1 locus (Msx1(nlacZ) allele), we detected segmental expression of the Msx1 gene in cells of the dorsal mesenchyme of the trunk between embryonic days 11 and 14. Replacing somites from a chick host embryo by murine Msx1(nlacZ )somites allowed us to demonstrate that these Msx1-(beta)-galactosidase positive cells are of somitic origin. We propose that these cells are dermal progenitor cells that migrate from the somites and subsequently contribute to the dorsalmost dermis. By analysing Msx1(nlacZ) expression in a Splotch mutant, we observed that migration of these cells does not depend on Pax3, in contrast to other migratory populations such as limb muscle progenitor cells and neural crest cells. Msx1 expression was never detected in cells overlying the dermomyotome, although these cells are also of somitic origin. Therefore, we propose that two somite-derived populations of dermis progenitor cells can be distinguished. Cells expressing the Msx1 gene would migrate from the somite and contribute to the dermis of the dorsalmost trunk region. A second population of cells would disaggregate from the somite and contribute to the dermis overlying the dermomyotome. This population never expresses Msx1. Msx1 expression was investigated in the context of the onset of dermis formation monitored by the Dermo1 gene expression. The gene is downregulated prior to the onset of dermis differentiation, suggesting a role for Msx1 in the control of this process.

Animals↗

Measles virus from a long-term persistently infected human T lymphoblastoid cell line, in contrast to the cytocidal parental virus, establishes an immediate persistence in the original cell line.

To investigate the mechanisms of measles virus (MV) establishment and maintenance of persistence in lymphoid cells, we have established a long-term persistent infection with MV, Edmonston strain, in the human T lymphoblastoid cell line MOLT4, which has been in continuous culture for over 8 years. In this culture, designated MOMP1, more than 98% of cells display viral antigens. The MOMP1 culture is immune to superinfection with MV and is not cured by anti-MV antibodies. No evidence of defective interfering particles was obtained. The persistently infected culture releases an infectious virus showing a miniplaque and thermoresistant modified phenotype that, unlike the parental virus Edmonston strain which produces a lytic infection with extensive cell fusion, establishes an immediate persistence in MOLT4 cells with neither significant loss of cell viability nor cell fusion. This suggests that the modification in the virus suffices to maintain the state of persistence without requiring a coevolution of the host cell during the infection, as has been reported in other persistent virus infections.

Antibodies, Viral↗

Cytological evidence for single-cell origin of tumors induced with 3-methylcholanthrene in female mice carrying Cattanach's translocation.

Chromosome studies were carried out on 12 tumors induced by subcutaneous injection of 0.005-0.5 mg of 3-methylcholanthrene in female mice carrying Cattanach's X-autosome translocation. Using the asynchronously replicating (hence genetically inactive) X chromosome as a marker, we obtained evidence showing that most or all of these tumors were monoclonal in origin. A single case, in which cell fusion occurred early in tumorigenesis, demonstrated that simultaneous expression of two different X chromosomes is not always incompatible with monoclonality.

Animals↗

Fetal gonadotrope cell origin of FSH-secreting pituitary adenoma - insight into human pituitary tumour pathogenesis.

OBJECTIVE: The pathogenesis of human pituitary adenomas remains unclear, but we report a case of FSH-secreting pituitary adenoma whose monohormonal phenotype suggests it was of fetal origin. PATIENTS: A 28-year-old woman presented with abdominal discomfort and irregular menses, enlarged multicystic ovaries and elevated serum oestradiol, with sustained high-normal FSH and low LH levels. MEASUREMENTS: Endocrine studies were performed before and after curative surgery, with assessment of tumour hormone secretion in vitro, and immunostaining of tumour tissue for a series of gonadotrope proteins. RESULTS: Immunocytochemistry showed that tumour cells were monohormonal for FSH. Normal components of gonadotrope signalling pathways were expressed, including oestrogen receptor-alpha, activin receptors, secretogranin-II and chromogranin-A. beta-glycan, the putative inhibin coreceptor, was absent. Tumour culture in vitro confirmed secretion of FSH with minimal LH, that was unsuppressed by oestradiol or inhibin-A. Human fetal pituitary tissue contained FSH-only cells at 18 weeks gestation, whereas normal adult pituitary tissue contained only bihormonal gonadotropes. CONCLUSIONS: We propose that this pituitary adenoma represents an indolent tumour of monohormonal fetal gonadotrope cells that originated early in gestation. Pituitary tumours may therefore arise from abnormal persistence of fetal cell types, with extremely slow growth over many years until reaching a size threshold to generate an endocrine syndrome. Understanding fetal pituitary architecture and function may be more informative for new insights into pituitary tumour pathogenesis than classical theories of cancer biology that invoke unrestrained cell proliferation.

Adenoma↗

Stem cell origin of cancer and differentiation therapy.

Our forefathers in pathology, on observing cancer tissue under the microscope in the mid-19th century, noticed the similarity between embryonic tissue and cancer, and suggested that tumors arise from embryo-like cells [Recherches dur le Traitement du Cancer, etc. Paris. (1829); Editoral Archiv fuer pathologische Anatomie und Physiologie und fuer klinische Medizin 8 (1855) 23]. The concept that adult tissues contain embryonic remnants that generally lie dormant, but that could be activated to become cancer was later formalized by Cohnheim [Path. Anat. Physiol. Klin. Med. 40 (1867) 1-79; Virchows Arch. 65 (1875) 64] and Durante [Arch. Memori ed Osservazioni di Chirugia Practica 11 (1874) 217-226], as the "embryonal rest" theory of cancer. An updated version of the embryonal rest theory of cancer is that cancers arise from tissue stem cells in adults. Analysis of the cellular origin of carcinomas of different organs indicates that there is, in each instance, a determined stem cell required for normal tissue renewal that is the most likely cell of origin of carcinomas [Lab. Investig. 70 (1994) 6-22]. In the present review, the nature of normal stem cells (embryonal, germinal and somatic) is presented and their relationships to cancer are further expanded. Cell signaling pathways shared by embryonic cells and cancer cells suggest a possible link between embryonic cells and cancer cells. Wilm's tumors (nephroblastomas) and neuroblastomas are presented as possible tumors of embryonic rests in children. Teratocarcinoma is used as the classic example of the totipotent cancer stem cell which can be influenced by its environment to differentiate into a mature adult cell. The observation that "promotion" of an epidermal cancer may be accomplished months or even years after the initial exposure to carcinogen ("initiation"), implies that the original carcinogenic event occurs in a long-lived epithelial stem cell population. The cellular events during hepatocarcinogenesis illustrate that cancers may arise from cells at various stages of differentiation in the hepatocyte lineage. Examples of genetic mutations in epithelial and hematopoietic cancers show how specific alterations in gene expression may be manifested as maturation arrest of a cell lineage at a specific stage of differentiation. Understanding the signals that control normal development may eventually lead us to insights in treating cancer by inducing its differentiation (differentiation therapy). Retinoid acid (RA) induced differentiation therapy has acquired a therapeutic niche in treatment of acute promyelocytic leukemia and the ability of RA to prevent cancer is currently under examination.

Antineoplastic Agents↗

Ossifying fibromyxoid tumor of soft parts: evidence supporting Schwann cell origin.

Immunohistochemical and ultrastructural studies of an ossifying fibromyxoid tumor of soft parts have been performed. Immunoreactivity of neoplastic cells for S-100 protein and glial fibrillary acidic protein, lack of immunoreactivity for type II collagen, and presence of basal lamina indicate that the tumor is of Schwann cell and not cartilaginous origin.

Aged↗

[Malignant histiocytosis: a study on clinicopathological features and cell origin].

Thirty-one autopsy cases previously diagnosed as malignant histiocytosis (MH) were studied by means of immunohistochemical staining. Antibodies detecting the formalin resistant epitopes on T-cells, B-cells and those of histiocyte/monocyte origin were used. It was shown that the malignant histiocytes reacted only to the cell markers derived from histiocyte/monocyte, and only a part of lymphocytes showed positive reaction to the T and B cell markers. It is suggested that the histiocyte/monocyte lineage is the possible origin of the malignant proliferating cells in MH. The clinicopathological features and the differentiation of MH from familial erythrophagocytic lymphohistiocytosis, virus-associated hemophagocytic syndrome and malignant lymphoma are described. The pathogenesis, the causes of death and the points for attention in the treatment of MH are also discussed.

Child↗

Stem-cell origin of metastasis and heterogeneity in solid tumours.

An explanation for the inherently metastatic and heterogeneous nature of cancers may be their derivation from distinct stem cells. The type of stem cell from which a neoplasm arises determines both the metastatic potential and the phenotypic diversity of that neoplasm. Hence, tumours originating from an early stem cell or its progenitor cells metastasise readily and have a more heterogeneous phenotype, whereas tumours originating from a later stem cell or its progenitor cells have limited metastatic potential and a more homogeneous phenotype. Further investigation of the role of stem cells in the development of cancer may lead to the discovery of novel diagnostic tools, prognostic markers, and therapeutic targets in the battle against cancer.

Biomarkers, Tumor↗

Properties of unitary IPSCs in hippocampal pyramidal cells originating from different types of interneurons in young rats.

Whole cell recordings were used in hippocampal slices of young rats to examine unitary inhibitory postsynaptic currents (uIPSCs) evoked in CA1 pyramidal cells at room temperature. Loose cell-attached stimulation was applied to activate single interneurons of different subtypes located in stratum oriens (OR), near stratum pyramidale (PYR), and at the border of stratum radiatum and lacunosum-moleculare (LM). uIPSCs evoked by stimulation of PYR and OR interneurons had similar onset latency, rise time, peak amplitude, and decay. In contrast, uIPSCs elicited by activation of LM interneurons were significantly smaller in amplitude and had a slower time course. The mean reversal potential of uIPSCs was -53.1 +/- 2.1 (SE) mV during recordings with intracellular solution containing potassium gluconate. With the use of recording solution containing the potassium channel blocker cesium, the reversal potential of uIPSCs was not significantly different (-58.5 +/- 2.6 mV), suggesting that these synaptic currents were not mediated by potassium conductances. Bath application of the gamma-aminobutyric acid-A (GABA(A)) receptor antagonist bicuculline (25 microM) reversibly blocked uIPSCs evoked by stimulation of all interneuron subtypes. In bicuculline, the mean peak amplitude of uIPSCs recorded with potassium gluconate was reduced to 3.5 +/- 4.4% of control (n = 7). Similarly, with cesium methanesulfonate, the mean amplitude in bicuculline was 2.9 +/- 3.1% of control (n = 13). Application of the GABA(B) receptor antagonist CGP 55845A (5 microM) resulted in a significant and reversible increase in the mean amplitude of uIPSCs recorded with cesium-containing intracellular solution. Thus uIPSCs from all cell types appeared under tonic presynaptic inhibition by GABA(B) receptors. Paired stimulation of individual interneurons at 100- to 200-ms intervals did not result in paired pulse depression of uIPSCs. For individual responses, a significant negative correlation was observed between the amplitude of the first and second uIPSCs. A significant paired pulse facilitation (154.0 +/- 8.0%) was observed when the first uIPSC was smaller than the mean of all first uIPSCs. A small, but not significant, paired pulse depression (90.8 +/- 4.0%) was found when the first uIPSC was larger than the mean of all first uIPSCs. Our results indicate that these different subtypes of hippocampal interneurons generate Cl(-)-mediated GABA(A) uIPSCs. uIPSCs originating from different types of interneurons may have heterogeneous properties and may be subject to tonic presynaptic inhibition via heterosynaptic GABA(B) receptors. These results suggest a specialization of function for inhibitory interneurons and point to complex presynaptic modulation of interneuron function.

Animals↗