Search PubMed⌕ Search

Biomedical subjects

J Bosch

Publications and source records attributed to J Bosch.

At least 37 records · Page 2Linked to original sources

Developing and establishing bee species as crop pollinators: the example of Osmia spp. (Hymenoptera: Megachilidae) and fruit trees.

The development of a bee species as a new crop pollinator starts with the identification of a pollination-limited crop production deficit and the selection of one or more candidate pollinator species. The process continues with a series of studies on the developmental biology, pollinating efficacy, nesting behaviour, preference for different nesting substrates, and population dynamics of the candidate pollinator. Parallel studies investigate the biology of parasites, predators and pathogens. The information gained in these studies is combined with information on the reproductive biology of the crop to design a management system. Complete management systems should provide guidelines on rearing and releasing methods, bee densities required for adequate pollination, nesting materials, and control against parasites, predators and pathogens. Management systems should also provide methods to ensure a reliable pollinator supply. Pilot tests on a commercial scale are then conducted to test and eventually refine the management system. The process culminates with the delivery of a viable system to manage and sustain the new pollinator on a commercial scale. The process is illustrated by the development of three mason bees, Osmia cornifrons (Radoszkowski), O. lignaria Say and O. cornuta (Latreille) as orchard pollinators in Japan, the USA and Europe, respectively.

Animals↗

Assessment of therapeutic benefit of antiviral therapy in chronic hepatitis C: is hepatic venous pressure gradient a better end point?

Chronic hepatitis C is a major healthcare problem. The response to antiviral therapy for patients with chronic hepatitis C has previously been defined biochemically and by PCR. However, changes in the hepatic venous pressure gradient (HVPG) may be considered as an adjunctive end point for the therapeutic evaluation of antiviral therapy in chronic hepatitis C. It is a validated technique which is safe, well tolerated, well established, and reproducible. Serial HVPG measurements may be the best way to evaluate response to therapy in chronic hepatitis C.

Antiviral Agents↗

Unprecedented oxidation of a phenylglycinol-derived 2-pyridone: enantioselective synthesis of polyhydroxypiperidines.

[reaction: see text]. The phenylglycinol-derived 2-pyridone 1 undergoes m-CPBA oxidation steroselectively leading to the chiral nonracemic unsaturated bicyclic hydroxylactam 2, from which the enantioselective synthesis of (3R,5R)-3,4,5-trihydroxypiperidine (16) and the formal synthesis of the azasugar epiisofagomine are described. The enantioselective synthesis of (S)-N-Boc-3-hydroxypiperidine and (3R,4S)-3,4-dihydroxypiperidine is also reported.

Enzyme Inhibitors↗

Ramipril and the development of diabetes.

CONTEXT: Type 2 diabetes is a growing clinical and public health problem. Preventive efforts related to lifestyle modification are not always successful; therefore, alternative prevention strategies need to be studied. OBJECTIVE: To investigate the effectiveness of ramipril, an angiotensin-converting enzyme inhibitor, in preventing diabetes among high-risk persons. DESIGN, SETTING, AND PARTICIPANTS: The randomized, controlled Heart Outcomes Prevention Evaluation trial of 5720 patients older than 55 years without known diabetes but with vascular disease who were followed up for a mean of 4.5 years. The study included 267 hospitals in 19 countries and was conducted between 1994 and 1999. INTERVENTION: Patients were randomly assigned to receive ramipril, up to 10 mg/d (n = 2837), or placebo (n = 2883). MAIN OUTCOME MEASURE: Diagnosis of diabetes determined from self-report at follow-up visits every 6 months, compared between the 2 groups. RESULTS: One hundred and two individuals (3.6%) in the ramipril group developed diabetes compared with 155 (5.4%) in the placebo group (relative risk [RR], 0.66; 95% confidence interval [CI], 0.51-0.85, P<.001). Similar results were noted when different diagnostic criteria were used; in the ramipril group, the RR for diagnosis of diabetes and hemoglobin A(1c) greater than 110% was 0.60 (95% CI, 0.43-0.85), for initiation of glucose-lowering therapy, 0.56 (95% CI, 0.41-0.77), and for both, 0.51 (95% CI, 0.34-0.76). These effects were also consistently seen in several subgroups examined. CONCLUSIONS: Ramipril is associated with lower rates of new diagnosis of diabetes in high-risk individuals. Because these results have important clinical and public health implications, this hypothesis requires prospective confirmation.

Aged↗

Reduction of cardiovascular risk by regression of electrocardiographic markers of left ventricular hypertrophy by the angiotensin-converting enzyme inhibitor ramipril.

BACKGROUND: Electrocardiographic markers of left ventricular hypertrophy (LVH) predict poor prognosis. We determined whether the ACE inhibitor ramipril prevents the development and causes regression of ECG-LVH and whether these changes are associated with improved prognosis independent of blood pressure reduction. METHODS AND RESULTS: In the Heart Outcomes Prevention Evaluation (HOPE) study, patients at high risk were randomly assigned to ramipril or placebo and followed for 4.5years. ECGs were recorded at baseline and at study end. We compared prevention/regression and development/persistence of ECG-LVH in the two groups and related these changes to outcomes. At baseline, 676 patients had LVH (321 in the ramipril group and 355 in the placebo group) and 7605 patients did not have LVH (3814 in the ramipril group and 3791 in the placebo group). By study end, 336 patients in the ramipril group (8.1%) compared with 406 in the placebo group (9.8%) had development/persistence of LVH; in contrast, 3799 patients in the ramipril group (91.9%) compared with 3740 in the placebo group (90.2%) had regression/prevention of LVH (P=0.007). The effect of ramipril on LVH was independent of blood pressure changes. Patients who had regression/prevention of LVH had a lower risk of the predefined primary outcome (cardiovascular death, myocardial infarction, or stroke) compared with those who had development/persistence of LVH (12.3% versus 15.8%, P=0.006) and of congestive heart failure (9.3% versus 15.4%, P<0.0001). CONCLUSIONS: The ACE inhibitor ramipril decreases the development and causes regression of ECG-LVH independent of blood pressure reduction, and these changes are associated with reduced risk of death, myocardial infarction, stroke, and congestive heart failure.

Aged↗

CD84 functions as a homophilic adhesion molecule and enhances IFN-gamma secretion: adhesion is mediated by Ig-like domain 1.

CD84 is a member of the CD2 subset of the Ig superfamily of cell surface molecules. Its cytoplasmic tail binds to Src homology 2 domain-containing protein 1A (signaling lymphocytic activation molecule-associated protein), a protein encoded by the X-linked lymphoproliferative disease gene. It is preferentially expressed on B lymphocytes, monocytes, and platelets. We show that it is also expressed on thymocytes and T cells. CD84 was positive on CD4-CD8- thymocytes, and its expression decreased with cell maturation. It is expressed on mature T cells preferentially on CD45RO+. To identify the CD84 ligand, we generated a soluble Ig fusion protein containing the human CD84 extracellular domains (CD84-Ig). Because receptor-ligand interactions occur between several members of this subfamily, we assayed CD84-Ig binding with all members of the CD2 family. CD84-Ig bound to CD84-transfected cells, whereas no binding was detected with cells expressing other CD2 subfamily receptors, showing that CD84 binds to itself. Anti-CD84 mAbs recognizing epitopes wholly within domain 1 of CD84 blocked the binding of the CD84-Ig fusion protein to CD84-transfected cells and platelets. Data from CD84 domain human/mouse chimeras further revealed that only the first extracellular domain of the molecule is involved in the ligand receptor recognition. The CD84-CD84 interaction was independent of its cytoplasmic tail. Finally, concurrent ligation of human CD84 with mAbs or CD84-Ig and CD3 enhanced IFN-gamma secretion in human lymphocytes. Thus, CD84 is its own ligand and acts as a costimulatory molecule.

Animals↗

Effects of ramipril on coronary events in high-risk persons: results of the Heart Outcomes Prevention Evaluation Study.

BACKGROUND: In trials of patients with left ventricular dysfunction or heart failure, ACE inhibitor use was unexpectedly associated with reduced myocardial infarction (MI). Using the Heart Outcomes Prevention Evaluation (HOPE) trial data, we tested prospectively whether ramipril, an ACE inhibitor, could reduce coronary events and revascularization procedures among patients with normal left ventricular function. METHODS AND RESULTS: In the HOPE trial, 9297 high-risk men and women, >/=55 years of age with previous cardiovascular disease or diabetes plus 1 risk factor, were randomly assigned to ramipril (up to 10 mg/d), vitamin E (400 IU/d), their combination, or matching placebos. During the mean follow-up of 4.5 years, there were 482 (10.4%) patients with clinical MI and unexpected cardiovascular death in the ramipril group compared with 604 (12.9%) in the placebo group [relative risk reduction (RRR), 21% (95% CI) (11,30); P<0.0003]. Ramipril was associated with a trend toward less fatal MI and unexpected death [4.0% versus 4.7%; RRR, 16% (-3, 31)] and with a significant reduction in nonfatal MI [5.6% versus 7.2%; RRR, 23% (9,34)]. Risk reductions in MI were documented in participants taking or not taking beta-blockers, lipid lowering, and/or antiplatelet agents. Although ramipril had no impact on hospitalizations for unstable angina [11.9% versus 12.2%; RRR, 3% (-9,14)], it reduced the risk of worsening and new angina [27.2% versus 30.0%; RRR, 12% (5,18); P<0.0014] and coronary revascularizations [12.5% versus 14.8%; RRR, 18%; (8,26) P<0.0005]. CONCLUSIONS: In this high-risk cohort, ramipril reduced the risk of MI, worsening and new angina, and the occurrence of coronary revascularizations.

Aged↗

Molecular characterization and expression of a novel human leukocyte cell-surface marker homologous to mouse Ly-9.

Ly-9 is a mouse cell-surface glycoprotein that is selectively expressed on thymocytes and on mature T and B lymphocytes. Ly-9 belongs to the CD2 subset of the immunoglobulin superfamily, an emerging family of cell signaling receptors. Recently, a partial human Ly-9 complementary DNA (cDNA) sequence has been described. Full-length cDNA clones were isolated that included the initiation codon, the sequence encoding the full signal peptide, and 14 amino acids more in the cytoplasmic domain than in the previously reported clone. The predicted extracellular domain of human Ly-9 contains 4 immunoglobulinlike domains, similar to those in mouse Ly-9. Northern blot analysis revealed that the human Ly-9 messenger RNA (2.6 kb) is expressed predominantly in lymph node, spleen, thymus, and peripheral blood leukocytes. Four monoclonal antibodies (mAbs) were raised against human Ly-9 by immunizing mice with the pre-B-cell line 300.19 stably transfected with human Ly-9 full-length cDNA. These mAbs strongly stained the surfaces of cells transfected with human Ly-9 cDNA but not of untransfected cells. Human Ly-9 expression was restricted to T and B lymphocytes and thymocytes, with the highest levels of expression on CD4(+)CD8(-) and CD4(-)CD8(+) thymocytes. Monocytes, granulocytes, platelets, and red blood cells were uniformly negative for Ly-9. These mAbs immunoprecipitated major polypeptides of 120 kd from the transfected cells and 120 kd and 100 kd from B-cell line Daudi, probably because of the cell-surface-expressed isoforms. These data demonstrate that human Ly-9 is a new marker for the study of normal and malignant leukocytes. (Blood. 2001;97:3513-3520)

Amino Acid Sequence↗

Generation and intermolecular reactions of 2-indolylacyl radicals.

The generation of 2-indolylacyl radicals from the corresponding phenyl selenoesters, aldehydes, and alpha-keto carboxylic acids and the scope of their participation in intermolecular addition reactions to carbon-carbon double bonds have been studied. Whereas the phenyl selenoester method has provided easy access to a variety of 1,4-dicarbonyl compounds bearing the 2-acylindole moiety, the glyoxylic acid route has been employed for the preparation of 2-indolyl pyridyl ketones.

Journal Article↗

Renal insufficiency as a predictor of cardiovascular outcomes and the impact of ramipril: the HOPE randomized trial.

BACKGROUND: The cardiovascular risk associated with early renal insufficiency is unknown. Clinicians are often reluctant to use angiotensin-converting enzyme inhibitors in patients with renal insufficiency. OBJECTIVE: To determine whether mild renal insufficiency increases cardiovascular risk and whether ramipril decreases that risk. DESIGN: Post hoc analysis. SETTING: The Heart Outcomes and Prevention Evaluation (HOPE) study, a randomized, double-blind, multinational trial involving 267 study centers. PATIENTS: 980 patients with mild renal insufficiency (serum creatinine concentration >/= 124 micromol/L [>/=1.4 mg/dL]) and 8307 patients with normal renal function (serum creatinine concentration < 124 micromol/L [<1.4 mg/dL]) Patients with a baseline serum creatinine concentration greater than 200 micromol/L (2.3 mg/dL) were excluded. MEASUREMENTS: The primary outcome measure was incidence of cardiovascular death, myocardial infarction, or stroke. RESULTS: Cumulative incidence of the primary outcome was higher in patients with renal insufficiency than in those without (22.2% vs. 15.1%; P < 0.001) and increased with serum creatinine concentration. Patients with renal insufficiency had a substantially increased risk for cardiovascular death (11.4% vs. 6.6%) and total mortality (17.8% vs. 10.6%) (P < 0.001 for both comparisons). The effect of renal insufficiency on the primary outcome (adjusted hazard ratio, 1.40 [95% CI, 1.16 to 1.69]) was independent of known cardiovascular risks and treatment. Ramipril reduced the incidence of the primary outcome in patients with and those without renal insufficiency (hazard ratio, 0.80 vs. 0.79; P > 0.2 for the difference). CONCLUSIONS: In patients who had preexisting vascular disease or diabetes combined with an additional cardiovascular risk factor, mild renal insufficiency significantly increased the risk for subsequent cardiovascular events. Ramipril reduced cardiovascular risk without increasing adverse effects.

Aged↗

Conjugate addition of organocuprates to chiral bicyclic delta-lactams. Enantioselective synthesis of cis-3,4-disubstituted and 3,4,5-trisubstituted piperidines.

[reaction: see text] Chiral nonracemic bicyclic lactam 3, easily accessible by cyclodehydration of (R)-phenylglycinol and racemic methyl 4-formylhexanoate, was converted to the unsaturated lactams 5, which undergo the stereoselective conjugate addition of lower order cyanocuprates to ultimately lead to enantiopure cis-3,4-disubstituted and 3,4,5-trisubstituted piperidines.

Heterocyclic Compounds, 2-Ring↗

Effects of ramipril and vitamin E on atherosclerosis: the study to evaluate carotid ultrasound changes in patients treated with ramipril and vitamin E (SECURE).

BACKGROUND: Activation of the renin-angiotensin-aldosterone system and oxidative modification of LDL cholesterol play important roles in atherosclerosis. The Study to Evaluate Carotid Ultrasound changes in patients treated with Ramipril and vitamin E (SECURE), a substudy of the Heart Outcomes Prevention Evaluation (HOPE) trial, was a prospective, double-blind, 3x2 factorial design trial that evaluated the effects of long-term treatment with the angiotensin-converting enzyme inhibitor ramipril and vitamin E on atherosclerosis progression in high-risk patients. METHODS AND RESULTS: A total of 732 patients >/=55 years of age who had vascular disease or diabetes and at least one other risk factor and who did not have heart failure or a low left ventricular ejection fraction were randomly assigned to receive ramipril 2.5 mg/d or 10 mg/d and vitamin E (RRR-alpha-tocopheryl acetate) 400 IU/d or their matching placebos. Average follow-up was 4.5 years. Atherosclerosis progression was evaluated by B-mode carotid ultrasound. The progression slope of the mean maximum carotid intimal medial thickness was 0.0217 mm/year in the placebo group, 0.0180 mm/year in the ramipril 2.5 mg/d group, and 0.0137 mm/year in the ramipril 10 mg/d group (P=0.033). There were no differences in atherosclerosis progression rates between patients on vitamin E and those on placebo. CONCLUSIONS: Long-term treatment with ramipril had a beneficial effect on atherosclerosis progression. Vitamin E had a neutral effect on atherosclerosis progression.

Aged↗

Purification, crystallization, and preliminary X-ray diffraction analysis of the Tricorn protease hexamer from Thermoplasma acidophilum.

Tricorn protease from Thermoplasma acidophilum is a hexameric enzyme; in vivo the hexamers assemble further to form large icosahedral capsids of 14.6 MDa. Recombinant Tricorn protease was purified as an enzymatically active hexamer of 0.72 MDa that formed crystals of octahedral morphology under low-ionic-strength conditions. These crystals belong to space group C2 with unit cell dimensions a = 307.5 A, b = 163.2 A, c = 220.9 A, beta = 105.5 degrees and diffract to 2.2-A resolution using high-brilliance synchrotron radiation. Based on analysis of the self-rotation function and the presence of a pseudo-origin peak in the native Patterson map, a packing model was derived for the complex, comprising 1.5 hexamers per asymmetric unit with a solvent content of 43%. Due to the ninefold noncrystallographic symmetry the Tricorn crystals represent an interesting case for phasing X-ray crystallographic data by electron microscopic phase information.

Archaeal Proteins↗

Female reciprocal calling in the Iberian midwife toad (Alytes cisternasii) varies with male call rate and dominant frequency: implications for sexual selection.

Male midwife toads (Alytes cisternasii) responded differently depending on the call frequency and call rate of other males. I tested female Iberian midwife toads with the same set of stimuli used earlier with males. Females responded faster to high call rates, and female vocal activity was greater in response to low-frequency male calls. Thus, in both sexes, the vocal response differs in the same direction according to signal frequency variation, but the magnitude of the response is greater in males than in females. In the light of these results, I discuss the implications for sexual selection of this reciprocal calling.

Animals↗

Comparative effects of the novel vasotocin analogue F-180 vs. vasopressin and terlipressin on systemic and splanchnic isolated vessels from portal hypertensive rats.

F-180 has been proposed as a new vasopressin analogue for the treatment of portal hypertension. This study investigates the contractile profile of F-180 compared to vasopressin and its analogue terlipressin on isolated systemic and splanchnic vessels from sham-operated and partial portal vein ligated (PPVL) rats. F-180 (10(-9)-10(-6) M), vasopressin (10(-11)-10(-8) M) and terlipressin (10(-9)-10(-4) M) induced contraction of the mesenteric vein, aorta, iliac, tail and mesenteric arteries. The order of potency in these vessels was vasopressin (pD2 approximately 9) > F-180 (pD2 approximately 8) > terlipressin (pD2 approximately 6). Significant (P<0.01) differences between sham-operated and PPVL rats were noticed exclusively in the mesenteric vein, being the maximal effect of the three agonists at least twice greater in PPVL rats than in sham-operated rats. The order of sensitivity to the vasoconstrictors in vessels from PPVL rats was aorta < mesenteric artery << iliac artery approximately equal tail artery approximately equal mesenteric vein. The contractile profile of these peptides in each vessel from PPVL animals was quite similar, except in the mesenteric vein and the aorta. F-180 showed higher efficacy (P<0.01) than terlipressin in the mesenteric vein and lower (P<0.05) efficacy than vasopressin in the aorta. These findings suggest the existence of a vasoconstrictor territorial selectivity for vasopressin and its analogues, which could justify the efficacy of these drugs in portal hypertension therapy. In particular, F-180 appears to be a viable alternative to the classic vasopressin analogues.

Animals↗