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Biomedical subjects

M D Ware

Publications and source records attributed to M D Ware.

8 recordsLinked to original sources
PubMed1997

Interleukin-3 induces the association of the inositol 5-phosphatase SHIP with SHP2.

We recently purified and cloned a 145-kDa protein that becomes tyrosine phosphorylated and associated with Shc in response to multiple cytokines. Based on its predicated amino acid sequence and its enzymatic activity, we have called this protein SHIP, for Src homology 2-containing inositol phosphatase. To gain further insight into the intracellular pathways that this putative signal transduction intermediate might regulate we have investigated whether SHIP binds to intracellular proteins other than Shc. The results presented herein demonstrate that following interleukin-3 stimulation, SHIP binds to the tyrosine phosphatase, SHP2 (also called Syp, PTP1D, SHPTP2, and PTP2C) and that Shc is not present in these SHIP-SHP2 complexes. Time course studies reveal that SHIP's association with SHP2 is transient and is maximal at 10 min of stimulation with interleukin-3. We further show that the association of SHIP with SHP2 occurs through the direct interaction of the SH2 domain of SHIP with a pYXN(I/V) sequence within SHP2.

Animals↗
PubMed1996

Cloning and characterization of human SHIP, the 145-kD inositol 5-phosphatase that associates with SHC after cytokine stimulation.

We recently cloned and sequenced a cDNA encoding a 145-kD protein from the murine hematopoietic cell line B6SUtA, that becomes tyrosine phosphorylated and associated with Shc after cytokine stimulation. Based on its domains and enzymatic activity, we named this protein SHIP for SH2-containing inositol phosphatase (Damen et al, Proc Natl Acad Sci USA 93:1689, 1996). We describe here the cloning of the human homologue of murine SHIP (mSHIP) from a human megakaryocytic cell line (MO7e) lambda gt11 cDNA library using two nonoverlapping mSHIP cDNA fragments as probes. Northern blot analysis suggests that human SHIP (hSHIP) is expressed as a 5.3-kb mRNA in human bone marrow and a wide variety of other tissues. Sequence analysis of this cDNA predicts a protein of 1188 amino acids exhibiting 87.2% overall sequence identity with mSHIP. Contained within the defined open reading frame is an N-terminal, group l src homology 2 (SH2) domain; three NXXY motifs that, if phosphorylated, could be bound by phosphotyrosine binding (PTB) domains; a C-terminal proline-rich region; and two centrally located inositol polyphosphate 5-phosphatase motifs. Fluorescence in situ hybridization, using the full-length hSHIP cDNA as a probe, mapped hSHIP to the long arm of chromosome 2 at the border between 2q36 and 2q37.

Adaptor Proteins, Signal Transducing↗
PubMed1984

Coagulation and fibrinolysis in estrogen-treated surgically menopausal women.

The short-term effects of different types and doses of estrogen therapy on coagulation and fibrinolysis were studied in 35 surgically menopausal women. Dynamic tests of the coagulation cascade, tests indicative of ongoing, intravascular coagulation, and assessments of coagulation inhibition and fibrinolysis were performed. No clinically abnormal responses were found with the tested regimens--1 and 2 mg of 17 beta-estradiol and 0.625 and 1.25 mg of conjugated equine estrogens. Increased plasminogen antigen and activity were found with the conjugated estrogens but not with the 17 beta-estradiol preparations. The age of the woman had no effect on either the direction or magnitude of response to treatment. Estrogen therapy at the reported doses does not appear to adversely affect the coagulation-fibrinolysis systems of surgically menopausal women. Based on their ability to enhance plasminogen activity, conjugated estrogens may be preferred over the 17 beta-estradiol preparations for this clinical population.

Adult↗
PubMed1983

Lipids and lipoproteins in women after oophorectomy and the response to oestrogen therapy.

The short-term effects of different types and doses of oestrogen on serum lipids and lipoproteins were studied in 35 oophorectomized women. After 3 months treatment, serum cholesterol levels were unaffected by 1 and 2 mg of micronized 17 beta-oestradiol or 0.625 and 1.25 mg of conjugated equine oestrogens. Triglyceride levels were significantly elevated after treatment with 1.25 mg of conjugated oestrogens. A trend towards a higher relative proportion of high-density lipoproteins and a lower relative proportion of low-density lipoproteins was observed for all four oestrogen regimens, however, statistical significance was not achieved. The proportion of very-low-density lipoprotein was unaffected by oestrogen treatment. The age of the oophorectomized women was found to have no effect on either the direction or magnitude of the lipid or lipoprotein responses to oestrogen. Using FSH depression as an index, 1.25 mg of conjugated oestrogens was found to be the most potent of the four oestrogen regimens tested. Therefore, with respect to lipid balance, little additional clinical benefit is achieved by using a more potent regimen and the risk of adverse side effects may be increased.

Adult↗
PubMed1982

Oestrogen--progestin therapy and the lipid balance of post-menopausal women.

The lipid and lipoprotein profiles of 20 post-menopausal women treated with cyclic conjugated oestrogens (0.625 or 1.25 mg) and medroxyprogesterone acetate (10 mg for 7 days) were compared to those of 18 untreated women of similar age and menopausal status. No statistically significant between-group differences were observed during the 18-mth period for cholesterol, triglycerides or lipoprotein distribution. After 12 mth, a significant shift in lipoprotein distribution manifested in the treated and untreated groups. The proportion of high-density lipoproteins significantly increased and that of the low-density lipoproteins significantly decreased. Although the shift was more pronounced in the treated group, there was no significant difference between the treated and untreated groups. These results indicated that such relatively nonandrogenic progestins as medroxyprogesterone acetate, have no adverse effects on the lipid milieu of post-menopausal women when used with long-term oestrogen therapy.

Cholesterol↗
PubMed1981

Benzodiazepines decrease grooming in response to novelty but not ACTH or beta-endorphin.

Excessive grooming in response to intracerebroventricular (ICV) ACTH1-24 was assayed following various doses of diazepam, chlordiazepoxide and flurazepam. Grooming scores were only affected by doses of the benzodiazepines higher than those that depressed locomotor activity. Similarly, diazepam did not affect excessive grooming induced by ICV beta-endorphin, nor did chronic chlordiazepoxide affect ACTH-induced grooming. By contrast similar doses of the benzodiazepines decreased the increased grooming score observed when mice were observed in a novel as opposed to the home cage. This result is consistent with the hypothesis that novel cage-induced grooming is caused by an increase in the ventricular content of ACTH or beta-endorphin, and that the benzodiazepines decrease or prevent this increase. It is not consistent with hypotheses of a functional antagonism between ACTH and benzodiazepines, at least insofar as the mechanisms involved in the production of grooming are concerned.

Adrenocorticotropic Hormone↗