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Biomedical subjects

M Keys

Publications and source records attributed to M Keys.

11 recordsLinked to original sources
PubMed1999

Target genes and regulatory domains of the GAMYB transcriptional activator in cereal aleurone.

GAMYB is an MYB transcription factor which is expressed in cereal aleurone cells in response to gibberellin (GA). HvGAMYB binds to the TAACAAA box of a high-pl alpha-amylase gene promoter and transcriptionally activates its expression. In this study, we examined the role of HvGAMYB in activating expression of other GA-regulated genes encoding hydrolytic enzymes. In transient expression experiments, HvGAMYB transactivated expression of reporter genes fused to a low-pl alpha-amylase gene promoter, an EII (1-3, 1-4)-beta-glucanase gene promoter and a cathepsin B-like protease promoter. HvGAMYB DNA binding specificity was determined using a PCR-based random site selection using HvGAMYB fusion protein isolated from E. coli. The deduced consensus closely resembled gibberellin response elements in alpha-amylase promoters. Functional analysis of HvGAMYB by transient expression of C terminal HvGAMYB deletions in barley aleurone cells identified two transcriptional activation domains (TADs) which function in transcriptional regulation of both high- and low-pl alpha-amylase promoters. The same TADs were identified using a heterologous yeast expression system. Together, these results indicate that HvGAMYB has two TADs. These domains are C-terminal to its DNA-binding domain.

Base Sequence↗
PubMed1997

Health visitors' reactions to implementing skill mix.

This article describes a small-scale qualitative study of health visitors' experiences of skill mix. The author finds that the implementation of skill mix has been more successful where health visitors have control over the process and are supported during the change.

Attitude of Health Personnel↗
PubMed1997

Cloning of a rice cDNA encoding a transcription factor homologous to barley GAMyb.

A cDNA clone, OsGAmyb, which encodes a homologue to the barley Myb-like transcription factor, HvGAMyb, was isolated from a rice endosperm cDNA library. The clone was used to show that expression of the OsGAmyb gene in aleurone cells was stimulated by gibberellic acid and the gene product was shown to transactivate an alpha-amylase gene promoter in transient expression analyses.

Amino Acid Sequence↗
PubMed1996

Double-blind placebo-controlled study of velnacrine in Alzheimer's disease.

The present study assessed the safety and efficacy of the cholinesterase inhibitor, velnacrine, for treating the cognitive symptoms of Alzheimer's disease. Patients (N = 236) meeting NINCDS-ADRDA criteria for Alzheimer's disease entered a double-blind, placebo-controlled dose-ranging protocol (30, 75, 150, 225 mg/day each for one week) to identify velnacrine responders (> or = four point improvement on the cognitive subscale of the Alzheimer's Disease Assessment Scale [ADAScog]). After a two week drug washout, velnacrine responders were randomly assigned to their best velnacrine dose or placebo in a six week dose-replication protocol employing the ADAScog and the Clinical Global Improvement scale as primary outcome measures. During dose-replication, intent-to-treat analysis revealed that velnacrine patients scored significantly better than placebo patients on the ADAScog after two (p < 0.004), four (p < 0.025) and six (p < 0.001) weeks of treatment. No significant treatment effect on Clinical Global Improvement scores was observed. The primary adverse event was an asymptomatic elevation of liver transaminases found among 28% of the 236 treated patients. Cholinergic side effects including diarrhea (14%), nausea (11%) and vomiting (5%) were observed and 8% of patients experienced skin rash. The present study identified a subgroup of Alzheimer's patients who demonstrated a significant, but modest, improvement during velnacrine treatment on structured cognitive testing.

Aged↗
PubMed1988

The contributions of adrenal hormones, hemodynamic factors, and the endotoxin-related stress reaction to stable prostaglandin analog-induced peripheral lymphopenia and neutrophilia.

Stable prostaglandin analogs are known to induce lymphopenia and neutrophilia in a dose-dependent fashion after subcutaneous injection in rats. The purpose of the present investigation is to determine whether the prostaglandin-induced changes in circulating leukocytes might be secondary to hypotension with the ensuing release of adrenal hormones. The adrenal medullary catecholamine epinephrine was found to induce neutrophilia in both intact and adrenalectomized rats, and the glucocorticosteroid analog dexamethasone induced a profound lymphopenia in rats as reported by previous investigators. A stable analog of PGF2 alpha (15-S-15-methyl PGF2 alpha; M-PGF2 alpha) at the dose of 1 mg/kg induced marked systemic hypotension 1 h after injection, with lymphopenia and neutrophilia 6 h after injection. The non-prostanoid hypotensive agent captopril, at a dose of 63 mg/kg, induced a hypotension of similar magnitude and kinetics to that induced by prostaglandin. Captopril also induced lymphopenia and neutrophilia at 6 h, although the neutrophilia was of lesser magnitude than that induced by prostaglandins. The prostaglandin-induced lymphopenia was found to be mediated, at least in part, by the hypotension-induced release of adrenal hormones, as evidenced by the abrogation of lymphopenia in prostaglandin-treated adrenalectomized rats. Captopril-treated adrenalectomized rats, however, did develop a significant lymphopenia, suggesting that hypotension can result in lymphopenia even in adrenalectomized rats. The M-PGF2 alpha-induced neutrophilia in adrenalectomized rats, by comparison to captopril-induced neutrophilia in adrenalectomized rats, was greater than the neutrophilia expected as the result of hypotension alone. Indeed, the M-PGF2 alpha-induced neutrophilia in adrenalectomized rats was greater than the captopril-induced neutrophilia in sham-adrenalectomized rats. Thus, a portion of the neutrophilia induced by M-PGF2 alpha in intact rats may be mediated through adrenal-independent, hemodynamic-independent mechanisms. The possibility that M-PGF2 alpha might be inducing neutrophilia via an endotoxin-like stress reaction was investigated by examining changes in circulating white blood cells in intact and adrenalectomized C3H/HeN (endotoxin-sensitive) and C3H/HeJ (endotoxin-resistant) mice after prostaglandin administration. No quantitative differences in the prostaglandin-induced neutrophilia were noted in C3H/HeJ mice as compared to the C3H/HeN mice.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenalectomy↗
PubMed1988

Silent nights.

Explore the source record for details and available documents.

Child, Preschool↗
PubMed1987

Kinetics and mechanisms of recombinant human interleukin 1 and tumor necrosis factor-alpha-induced changes in circulating numbers of neutrophils and lymphocytes.

Human recombinant interleukins 1 alpha and 1 beta (rIL-1 alpha and -1 beta) both induced monophasic peripheral neutrophilia and lymphopenia in Lewis rats 1.5 hr after i.v. injection. The kinetics of rIL-1 alpha- and -1 beta-induced neutrophilia were similar to those induced by human monocyte-derived IL-1, IL-1 alpha, and IL-1 beta, and the peripheral neutrophilia was accompanied by a marked decrease in marrow neutrophils. Arachidonic acid metabolites are implicated as biochemical intermediates in the production of the neutrophilia but not lymphopenia, since indomethacin and dexamethasone both completely abrogated IL-1-induced neutrophilia but did not affect the IL-1-induced lymphopenia. Acetylsalicylic acid, a cyclooxygenase inhibitor, did not inhibit IL-1-induced neutrophilia, suggesting that products of the lipoxygenase rather than the cyclooxygenase pathway of arachidonate metabolism may contribute to the neutrophilia. Human recombinant tumor necrosis factor-alpha (rTNF) administered i.v. to Lewis rats induced peripheral neutropenia, two peaks of neutrophilia, and lymphopenia. A wide range of doses of rTNF resulted in an initial neutropenia at 0.5 hr after injection followed by a first peak of neutrophilia at 1.5 hr and a second peak of neutrophilia at 6 hr. The initial neutropenia and the first peak of neutrophilia were not inhibited by pretreatment of rats with dexamethasone, indomethacin, or aspirin. The second peak of neutrophilia was inhibited by both dexamethasone and indomethacin, but was not at all inhibited by aspirin, suggesting that the second peak of neutrophilia is mediated by the release of endogenous cytokines, especially by IL-1, since exogenous IL-1-induced neutrophilia is also completely inhibited by dexamethasone and indomethacin but not by aspirin. The TNF-induced peripheral neutrophilia is also accompanied by a significant depletion of bone marrow neutrophils, indicating that the source of increased circulating neutrophils is, at least in part, via recruitment of marrow neutrophils. Systemic blood pressure was not affected by IL-1 or rTNF at the dosages employed, showing that the changes in circulating leukocyte subsets were not attributable to hemodynamic changes nor to the hemodynamic change-related release of adrenal hormones. Adrenalectomy did not alter the IL-1- or rTNF-induced neutrophilia or lymphopenia, also demonstrating that neither monokine mediates its hematologic effects on peripheral blood leukocytes via the release of adrenal hormones.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1987

Recombinant human alpha lymphotoxin (tumor necrosis factor-beta) induces peripheral neutrophilia and lymphopenia in the rat.

Recombinant human alpha lymphotoxin (rLT) administered intravenously to Lewis rats induces peripheral neutrophilia and lymphopenia in a dose-response dependent fashion. A dose of 30,000 units of rLT induced a neutrophilia (1589 +/- 326 to 5554 +/- 1050 neutrophils/cu mm) and lymphopenia (10,368 +/- 992 to 4636 +/- 878 lymphocytes/cu mm) at 2 hours after injection that was highly significant (P less than 0.001 and P less than 0.001, respectively) in comparison with vehicle controls. The kinetics of the neutrophilia that peaked at 2 hours as well as of the lymphopenia were highly reminiscent of the neutrophilia and lymphopenia following intravenous administration of either recombinant human interleukin-1 (IL-1) alpha or beta to rats. The peripheral neutrophilia was accompanied by a significant depletion of bone marrow neutrophils (P less than 0.001), as is also known to occur after administration of IL-1. Systemic blood pressure was not affected by rLT, which suggested that the changes in circulating leukocyte subsets were not attributable to hemodynamic changes nor to the hemodynamic-change-related release of adrenal hormones. Adrenalectomy did not alter the rLT-induced neutrophilia or lymphopenia, which suggested that rLT does not mediate its hematologic effects on peripheral blood leukocytes via the release of adrenal hormones. Pretreatment of rats with dexamethasone, indomethacin, or aspirin also did not alter rLT-induced neutrophilia or lymphopenia, which suggested that rLT-induced hematologic effects were not mediated via arachidonic acid metabolites, in stark contrast to IL-1 induced neutrophilia, which is inhibited by both dexamethasone and indomethacin.

Animals↗
PubMed1987

Stable analogs of prostaglandins E1 and F2 alpha ameliorate the proteinuria of aminonucleoside-of-puromycin nephrosis in Lewis rats.

Prostaglandins have been implicated by previous investigators in the pathogenesis of the nephrotic syndrome. A single subcutaneous injection of 1 mg/kg of stable analogs of prostaglandins E1 or F2 alpha (15[S]-15-methyl -PGE1 [M-PGE1] and -PGF2 alpha [M-PGF2 alpha]) was found in the present study to dramatically decrease proteinuria on Day 10 of puromycin aminonucleoside (PAN) nephrosis in Lewis rats. The decrease in proteinuria was mediated at least in part by a decrease in glomerular filtration rate (GFR), as quantitated by inulin clearances in nephrotic control and prostaglandin-treated rats. M-PGE1, moderately, and M-PGF2 alpha, to a lesser degree, also decreased the GFR in normal rats. Interestingly, the GFR was dramatically decreased in nephrotic as compared with nonnephrotic control rats, which suggests that PAN nephrosis may not be an ideal experimental model for human minimal change nephrosis in which the GFR is usually not severely compromised. The prostaglandin-induced decrease in GFR in both nephrotic and normal rats was coincident with a drop in systemic blood pressure. Nephrotic rats, however, had a slightly higher baseline blood pressure than normals, and the hypotensive effects of both prostaglandins were much less in nephrotic than in normal rats. The decrease in proteinuria was not related to a cytoprotective effect, as indicated by the failure of daily doses of 5 micrograms/kg M-PGE1 to reduce proteinuria 6, 8, or 10 days after injection of puromycin aminonucleoside. The similar antiproteinuric effects of prostaglandin synthesis inhibitors and of pharmacologic doses of prostaglandins are somewhat paradoxical but are reminiscent of the similarly paradoxical mutual antiinflammatory effects of these agents. The high doses of prostaglandins required to reduce proteinuria as well as their reduction of blood pressure and GFR will limit their clinical usefulness in the nephrotic syndrome.

Alprostadil↗