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Pathogen research abs 1 || Pathogen research abs 2 || Pathogen research abs 3 || Pathogen research abs 4 || Pathogen research abs 5 || Hormone and endocrine research abs 1 || Hormone and endocrine research abs 2 || Hormone and endocrine research abs 3 || Hormone and endocrine research abs 4 || Hormone and endocrine research abs 5 || Follicle and follicular cells research abs 1 || Interferon research abs 1 || Hemoglobin research abs || Stem cell research abs

J Cell Mol Med. 2002 Jan-Mar;6(1):59-73.
Neoductular progenitor cells regenerate hepatocytes in severely damaged liver: a comparative ultrastructural study.

Mandache E, Vidulescu C, Gherghiceanu M, Dragomir P, Popescu LM.

Victor Babes Institute of Pathology, Bucharest, Romania. empathobabes.ro

In severely injured liver, stem cells give rise to progeny that tend to replace lost hepatocytes. Neoductular reaction appears as an inherent stage of liver reconstruction following severe damage caused by different pathological mechanisms. Few ultrastructural types of progenitor cells have been described, and some molecular phenotypes of progenitor stages have been characterized, but the details of the differentiation process are largely unknown. We prepared for light and electron microscopy examination human liver from biopsies of patients with chronic active hepatitis, and rat liver with allyl alcohol-induced periportal necrosis. We found that progenitor neoductular cells acquire the hepatocytic polarity pattern during a multi-step process apparently involving cell migration and dissolution of neoductular basement membrane. An intermediate stage with "mixed" ductular and hepatocytic polarity was described.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12003669&dopt=Abstract

J Biol Chem. 2002 Jul 26;277(30):27294-304. Epub 2002 May 09.
Increased basal cAMP-dependent protein kinase activity inhibits the formation of mesoderm-derived structures in the developing mouse embryo.

Amieux PS, Howe DG, Knickerbocker H, Lee DC, Su T, Laszlo GS, Idzerda RL, McKnight GS.

Department of Pharmacology, University of Washington, Seattle, WA 98195, USA.

A targeted disruption of the RIalpha isoform of protein kinase A (PKA) was created by using homologous recombination in embryonic stem cells. Unlike the other regulatory and catalytic subunits of PKA, RIalpha is the only isoform that is essential for early embryonic development. RIalpha homozygous mutant embryos fail to develop a functional heart tube at E8.5 and are resorbed at approximately E10.5. Mutant embryos show significant growth retardation and developmental delay compared with wild type littermates from E7.5 to E10.5. The anterior-posterior axis of RIalpha mutants is well developed, with a prominent head structure but a reduced trunk. PKA activity measurements reveal an increased basal PKA activity in these embryos. Brachyury mRNA expression in the primitive streak of RIalpha mutants is significantly reduced, consistent with later deficits in axial, paraxial, and lateral plate mesodermal derivatives. This defect in the production and migration of mesoderm can be completely rescued by crossing RIalpha mutants to mice carrying a targeted disruption in the Calpha catalytic subunit, demonstrating that unregulated PKA activity rather than a specific loss of RIalpha is responsible for the phenotype. Primary embryonic fibroblasts from RIalpha mutant embryos display an abnormal cytoskeleton and an altered ability to migrate in cell culture. Our results demonstrate that unregulated PKA activity negatively affects growth factor-mediated mesoderm formation during early mouse development.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12004056&dopt=Abstract

Clin Lymphoma. 2002 Sep;3(2):97-104.
Gemcitabine and its combinations in the treatment of malignant lymphoma.

Chau I, Watkins D, Cunningham D.

Department of Medicine, Royal Marsden Hospital, Sutton, Surrey, United Kingdom. ian.chamh.nthames.nhs.uk

Although combination chemotherapy can induce complete remission in a large proportion of patients with Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL), 30%-50% of patients will relapse. Gemcitabine has shown promising activity in heavily pretreated patients with HD and NHL even in those who have progressed after autologous stem cell transplantation. Its favorable toxicity profile allows development of combination regimens with other cytotoxic drugs and anti-CD20-targeted therapy, although hematologic toxicities appear to be greater than when gemcitabine is used as a single agent. Prolonged infusion of gemcitabine at a pharmacologically guided dose rate of 10 mg/m2/minute has demonstrated a pharmacokinetic and pharmacodynamic advantage although clinical efficacy of prolonged infusion needs to be established. Thus far, gemcitabine has been mainly tested in relapsed or refractory patients, and its inclusion in front-line therapy may bring about greater benefit. However, as gemcitabine has not been evaluated in randomized studies either alone or in combination with other chemotherapy drugs, its exact role in the treatment paradigm of lymphoma remains to be determined.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12435288&dopt=Abstract [PubMed - in process]

Stem Cells. 2002;20(3):230-40.
Modeling stem cell development by retrospective analysis of gene expression profiles in single progenitor-derived colonies.

Madras N, Gibbs AL, Zhou Y, Zandstra PW, Aubin JE.

Department of Mathematics and Statistics, York University, Toronto, Ontario, Canada.

The process of development of various cell types is often based on a linear or deterministic paradigm. This is true, for example, for osteoblast development, a process that occurs through the differentiation of a subset of primitive fibroblast progenitors called colony-forming unit-osteoblasts (CFU-Os). CFU-O differentiation has been subdivided into three stages: proliferation, extracellular matrix development and maturation, and mineralization, with characteristic changes in gene expression at each stage. Few analyses have asked whether CFU-O differentiation, or indeed stem cell differentiation in general, may follow more complex and nondeterministic paths, a possibility that may underlie the substantial number of discrepancies in published reports of progenitor cell developmental sequences. We analyzed 99 single colonies of osteoblast stem/primitive progenitor cells cultured under identical conditions. The colonies were analyzed by global amplification poly(A) polymerase chain reaction to determine which of nine genes had been expressed. We used the expression profiles to develop a statistically rigorous map of the cell fate decisions that occur during osteoprogenitor differentiation and show that different developmental routes can be taken to achieve the same end point phenotype. These routes appear to involve both developmental "dead ends" (leading to the expression of genes not correlated with osteoblast-associated genes or the mature osteoblast phenotype) and developmental flexibility (the existence of multiple gene expression routes to the same developmental end point). Our results provide new insight into the biology of primitive progenitor cell differentiation and introduce a powerful new quantitative method for stem cell lineage analysis that should be applicable to a wide variety of stem cell systems.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12004081&dopt=Abstract

Stem Cells. 2002;20(3):241-8.
A new assay method for late CFU-S formation and long-term reconstituting activity using a small number of pluripotent hemopoietic stem cells.

Yang G, Hisha H, Cui Y, Fan T, Jin T, Li Q, Lian Z, Hosaka N, Li Y, Ikehara S.

First Department of Pathology, Transplantation Center, and Regeneration Research Center for Intractable Diseases, Kansai Medical University, Moriguchi City, Osaka, Japan.

We have previously reported that Lin-/CD71-/MHC class Ihigh/c-kit<low bone marrow cells (c-kit<low cells) are pluripotent hemopoietic stem cells (P-HSCs), since they have the capacity to self-renew for at least 2 years in mice and differentiate into all hemopoietic lineage cells over the long term when serial bone marrow transplantation is carried out using 500 c-kit<low cells. In addition, we have found that the c-kit<low cells do not form colony-forming units-spleen (CFU-S) on days 8 to 14 but form late CFU-S (after 16 days). In the present study, to confirm that c-kit<low cells are truly P-HSCs, we examine whether a few (< or = 50) c-kit<low cells can form late CFU-S and reconstitute lethally irradiated recipients. We have established a new method to rescue lethally irradiated mice by transplantation of a few cells so that they survive for more than 16 days: 0.2 ml of 20 Gy-irradiated peripheral blood (PB) was injected into the recipients every 3 days. All the mice that had been transplanted with 25 or 50 c-kit<low cells alone died within 12 days, and no CFU-S were detected in their spleens. However, when 25 or 50 c-kit<low cells were injected and 0.2 ml of 20 Gy-irradiated PB was injected every 3 days, the recipients survived, and a small number of CFU-S were detected after 16 days. About 40% of the recipients injected with 50 c-kit<low cells and about 15% of those injected with 25 c-kit<low cells survived for more than 6 months. Moreover, donor-derived multilineage cells were detected in all the hematolymphoid organs of the recipient mice. This new assay method using a small number of cells would be of great advantage for clarifying which cells are truly P-HSCs.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12004082&dopt=Abstract

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