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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







Haematologica. 2000 Nov;85(11):1153-7.
Need for an accurate molecular diagnosis to assess the donor origin of leukemia relapse after allogeneic stem cell transplantation.

Spinelli O, Giussani U, Borleri G, Lazzari M, Michelato A, Dotti G, Barbui T, Rambaldi A.

Divisione di Ematologia e Centro Trasfusionale, Ospedali Riuniti di Bergamo, Italy.

BACKGROUND AND OBJECTIVES: Leukemia relapse occurring in donor cells after allogeneic hematopoietic stem cell transplantation has been reported in rare cases. Cytogenetic analysis and molecular probing of variable number of tandem repeats (VNTRs) have been used to confirm this unusual event in the few cases so far reported in the literature. The aim of this study was to demonstrate that extensive molecular characterization of leukemic cells at diagnosis and relapse may be necessary to avoid many technical pitfalls possibly leading to an erroneous diagnosis of leukemia relapse in donor cells after allogeneic transplantation. DESIGN AND METHODS: We report the case of a 49- year old man who received an allogeneic transplantation from his HLA-identical sister because of BCR-ABL+ acute lymphoblastic leukemia (ALL). After having achieved complete hematologic and molecular remission, two years later an overt leukemia relapse occurred with cytogenetic findings suggesting a leukemia relapse in donor cells. The donor or patient origin of leukemic cells at relapse was further investigated by fluorescence in situ hybridization (FISH) karyotyping, reverse transcription (RT) polymerase chain reaction (PCR) analysis of BCR-ABL chimeric transcripts, PCR amplification of several VNTRs and the Y chromosome-specific DYS14 sequence and finally by amplification, cloning and sequencing of the CDRIII region of the immunoglobulin heavy chain (IgH) gene. RESULTS: At the time of relapse, conventional and FISH karyotyping revealed the presence of a Phl+ chromosome and a female karyotype in all the 25 metaphases analyzed and PCR amplification of the Y chromosome-specific DYS14 sequence was negative. Moreover, the molecular evaluation of hematopoietic chimerism performed by the NZ-22 VNTR allowed us to demonstrate that at the time of relapse, a consistent proportion of hematopoietic cells was of donor origin. However, the molecular cloning and sequencing of the CDRIII region of the immunoglobuin heavy chain (IgH) gene rearrangement in leukemic blasts at diagnosis and relapse demonstrated their identity thus formally proving the patient origin of both leukemic clones. INTERPRETATION AND CONCLUSIONS: While the simplest interpretation of the apparent female karyotype at relapse is the consequence of a loss of the Y chromosome which in leukemic blasts took place along with duplication of an X-chromosome, this case strongly emphasizes the need for accurate and extensive molecular characterization to prove the donor origin of a leukemia relapse after allogeneic transplantation.


online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11064467&dopt=Abstract



Nat Med. 2000 Nov;6(11):1235-40.
Stem cell repopulation efficiency but not pool size is governed by p27(kip1).

Cheng T, Rodrigues N, Dombkowski D, Stier S, Scadden DT.

Massachusetts General Hospital AIDS Research Center, Harvard Medical School, 149 13th Street, Room 5212 Boston, Massachusetts 02129, USA. cheng-tagh.harvard.edu

Sustained blood cell production requires preservation of a quiescent, multipotential stem cell pool that intermittently gives rise to progenitors with robust proliferative potential. The ability of cells to shift from a highly constrained to a vigorously active proliferative state is critical for maintaining stem cells while providing the responsiveness necessary for host defense. The cyclin-dependent kinase inhibitor (CDKI), p21(cip1/waf1) (p21) dominates stem cell kinetics. Here we report that another CDKI, p27(kip1) (p27), does not affect stem cell number, cell cycling, or self-renewal, but markedly alters progenitor proliferation and pool size. Therefore, distinct CDKIs govern the highly divergent stem and progenitor cell populations. When competitively transplanted, p27-deficient stem cells generate progenitors that eventually dominate blood cell production. Modulating p27 expression in a small number of stem cells may translate into effects on the majority of mature cells, thereby providing a strategy for potentiating the impact of transduced cells in stem cell gene therapy.


online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11062534&dopt=Abstract



Harefuah. 2000 Sep;139(5-6):174-9, 248, 247.
[High-dose chemotherapy and autologous stem cell transplantation for refractory and relapsing Hodgkin's disease as first-line therapy-- studies at Sheba Medical Center--Tel Hashomer]

[Article in Hebrew]

Avigdor A, Hardan I, Shpilberg O, Raanani P, Grotto I, Ben-Bassat I.

High dose chemotherapy and autologous stem cell transplantation are widely used in relapsed and primary refractory Hodgkin's disease. We transplanted 42 patients with Hodgkin's disease between 1990-1998. Median follow-up was 31 months (range 1-102). 29 (69%) were transplanted after relapse and 13 (31%) were refractory to first line therapy. Median age at transplantation was 29 years (range 19-58) and 23 (55%) were males. All were treated with the BEAM protocol (carmustine, etoposide, cytarabine and melphelan). 18 who were in remission received radiotherapy following transplantation. The source of the stem cells was bone marrow in 17% and peripheral blood in 83%. At initial diagnosis: 57% had stage III-IV disease and B symptoms were present in 52%. 75% were treated with MOPP, ABVD or with related versions. Radiotherapy followed in 52%. Prior to transplantation, 45% of the relapsed group were in the advanced stage. 33% and 12% of all patients had lung and bone involvement, respectively. The complete remission rate was 86% for the 2 groups. 2 (5%) died from transplant-related complications and MDS/AML developed in 2 (5%) after transplantation. The 3-year overall survival (OS) and disease-free survival (DFS) were 68% and 60%, respectively. The 3-year OS for the relapsed group was 64% compared with 76% for the refractory group, and the 3-year DFS for the relapsed group was 60% vs. 42% for the refractory group (neither difference significant). Radiotherapy following transplantation did not have a beneficial effect on DFS. No prognostic factors for outcome of transplantation were found, most probably due to the limited number of patients and the high variability of disease characteristics. We conclude that high dose chemotherapy and autologous stem cell transplantation are effective and relatively safe for relapsed or primary refractory Hodgkin's disease. The DFS at 3 years was longer for those transplanted after relapse than those with primary refractory disease, but not significantly. Patients with primary refractory disease can be salvaged with high dose chemotherapy.


online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11062945&dopt=Abstract



Exp Hematol. 2000 Nov;28(11):1286-96.
Identification of four human cDNAs that are differentially expressed by early hematopoietic progenitors.

Zhang X, Dormady SP, Basch RS.

Department of Pathology and the Kaplan Comprehensive Cancer Center, New York University School of Medicine, New York, NY, USA.

The molecular processes that maintain the stem cell pool are largely unknown. Using polymerase chain reaction-driven subtraction, we examined genes that are differentially expressed by early hematopoietic progenitors. We expected that identifying genes that are uniquely expressed by the earliest precursors would provide insight into the mechanism(s) through which stem cell number is maintained and differentiation is regulated.Using CD34(+)CD38(-) cells as starting material, we identified four mRNAs, expressed by these cells, that are either absent or present in reduced amounts in more mature CD34(+)CD38(+) cells. One of these cDNAs (C40) encodes a known member of the subfamily of protein phosphatases (CL100) that exhibits dual substrate specificity for phosphotyrosine- and phosphoserine/threonine-containing substrates and specifically inactivates MAP kinases. This phosphatase has been shown to play a role in regulating the differentiation of several cell types. The second cDNA (C23) is identical to LR11 (gp250), a member of the low-density lipoprotein receptor family. LR11 is unusual in that, in addition to 11 ligand-binding repeats, it contains a series of fibronectin type III repeats near its carboxyl terminal end that are similar to those found in cytokine receptors. It is highly expressed in developing brain, but hematopoietic expression has not been reported. The 178-bp fragment that we originally cloned is part of a 4,145-bp 3' untranslated region (UTR) that had not been previously sequenced and is among the largest human 3' UTRs ever reported. The other isolates (C21 and C12) do not correspond to known protein sequences. They are homologous to EST sequences from a fetal brain library. C21 encodes a previously unknown gene that is a member of the WD-40 family. An open reading frame encoding a 515 amino acid protein has been identified.Four mRNAs, differentially expressed by CD34(+)CD38(-) human bone marrow cells, have been identified. Although this population is highly enriched for early hematopoietic progenitors, none of these genes encodes a message whose expression is limited to the hematopoietic system. They all are expressed in a variety of tissues, suggesting that they are involved in processes that are fundamental to the development of many cell types. All of these cDNAs possess atypically long 3' UTRs, and one of them is among the longest ever described. Their differential expression by immature hematopoietic cells, in contrast to more mature cells, suggest that long 3' UTRs may be characteristic of genes that play a regulatory role during development.


online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11063877&dopt=Abstract



Rheumatol Int. 2000;19(6):235-41.
An unusual case of systemic lupus erythematosus, lupus nephritis, and transient monoclonal gammopathy.

Strobel ES, Fritschka E, Schmitt-Graff A, Peter HH.

Department of Medicine, Klinikum der Albert-Ludwigs-Universitat Freiburg, Germany.

A 23-year-old female patient suffering from active systemic lupus erythematosus (SLE) was treated with azathioprine (2 mg/kg per day) and prednisone. Lupus nephritis class III with increasing proteinuria developed 28 months after disease onset. Treatment was switched to monthly pulse cyclophosphamide administered intravenously for 6 months (total dose 6.3 g), followed by oral azathioprine and low-dose prednisone to maintain partial remission. Eight months later, the patient developed an acute exacerbation of SLE with fever, proteinuria of 9.1 g/day, pancytopenia, and cerebral involvement with cephalgias and a grand mal seizure. She responded well to high-dose corticosteroids (500 mg prednisolone pulses over 3 days, i.v.) and was azathioprine switched from to methotrexate (12.5-15 mg per week). Under this treatment, lupus activity gradually decreased and the patient felt well again. Five years after the initial diagnosis of SLE, a rapidly increasing immunoglobulin G-kappa type (IgG-kappa) monoclonal gammopathy developed, reaching a maximal serum paraprotein concentration of 73.5 g/l. Bone marrow biopsy revealed 15% of moderately abnormal, highly differentiated plasma cells arranged in small clusters and expressing IgG-kappa. No bony lesions were detectable on skeletal radiographs. Pulses of dexamethasone (40 mg) were administered and led to a transient decrease of paraproteinemia to a minimum of 31.9 g/l, followed by an increase to 62 g/l. At that point, high-dose chemotherapy supported by autologous stem cell transplantation was considered. Due to an intermittent pneumococcal septicemia, methotrexate was discontinued and dexamethasone was replaced by 5-10 mg cloprednol. At this point, totally unexpectedly, the paraprotein decreased spontaneously without any further cytostatic treatment and was no longer detectable 1 year later. Concomitantly, plasma cell counts in bone marrow biopsies fell to below 5%. As SLE remained inactive, the patient became pregnant and gave birth to a healthy child. During late pregnancy, SLE activity flared up with rising proteinuria and blood pressure. Therefore, after delivery, cyclophosphamide (100 mg/day, orally) was readministered for 4 months, resulting in an improvement of kidney function with stable proteinuria of 1-2 g/l to date. Paraproteins are no longer detectable. In conclusion, this case report documents the rare event of transient paraproteinemia in a patient with SLE. A self-limiting regulatory defect in the control of a terminally differentiated B-cell clone may be the origin of this phenomenon.


online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11063295&dopt=Abstract








Natural Herbal Supplement: Hair Million


Hair loss alone does not pose significant health problems. In fact, there are people who opt for baldness as an alternative hair style. However, in general, however, hair loss is not considered desirable.

The most ostensive feature that distinguishes us human from chimps and other primates is the lack of bodily hair. During evolutionary process, we have lost the majority of hair. Hair is no longer a biologically essential part of our body, just like appendix. The hair we still have on our scalp and a few other bodily parts is still regarded as significant for reasons other than biological necessity. Hair loss is naturally accompanied by aging process, although the extent of hair loss and the timing of onset vary widely among individuals. Thus, loss of hair and baldness is considered as a symbol of maturity or old age. Like winkles and other signs of aging, hair loss is not welcome by most people, because we don't welcome aging, and being perceived as an aging person. However, it is alopecia, or premature hair loss that especially concerns certain people.

While the hair loss and resulting baldness in general have not been proven to be related to underlying health problems, there are certain correlations between hair loss and health problems. For instance, premature hair loss could suggest premature aging or nutritional and hormonal imbalance, stressful life, use of drugs that cause hair loss as a side effect, skin disease, or heart disease. The balding appearance could also impart a subdued impression of integrity in bodily health and youthfulness.














DHEA is a natural hormone, and it is produced in our body by the adrenal glands. DHEA has been suggested to provide numerous potential benefits. DHEA (or dehydroepiandrosterone) is converted into androgens (male hormones) or estrogens (female hormones) in the cells. Our bodies produce decreasing amount of DHEA as we get older. various health benefits: To deter aging, improve sexual function/erectile dysfunction, treat cognitive decline, enhance athletic performance, facilitate weight loss, improve strength, prevent osteoporosis, enhance immunomodulation for rheumatic conditions, and treat depression.







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