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Biomedical subjects

J Mann

Publications and source records attributed to J Mann.

At least 37 records · Page 2Linked to original sources
PubMed2003

Experimental studies of occupation times in turbulent flows.

The motion of passively convected particles in turbulent flows is studied experimentally in approximately homogeneous and isotropic turbulent flows, generated in water by two moving grids. The simultaneous trajectories of many small passively convected, neutrally buoyant, polystyrene particles are followed in time by a particle tracking technique. We estimate the probability distribution of the occupation times of such particles in spherical volumes with a given radius. A self-consistently moving particle defines the center of the reference sphere, with the occupation time being defined as the difference between entrance and exit times of surrounding particles convected through the sphere by the turbulent motions. Simple, and seemingly universal, scaling laws are obtained for the probability density of the occupation times in terms of the basic properties for the turbulent flow and the geometry. In the present formulation, the results of the analysis are relevant for understanding details in the feeding rate of micro-organisms in turbulent waters, for instance.

Journal Article↗
PubMed2003

Mechanistic and anti-proliferative studies of two novel, biologically active bis-benzimidazoles.

We have previously synthesised a number of novel head-to-head bis-benzimidazole derivatives that are structurally related to the fluorochrome, Hoechst 33258, and which possess strong affinity for A:T sites in the minor groove of duplex DNA. Initial studies revealed these compounds to exhibit potent antiproliferative activity against a range of ovarian cell lines and to inhibit transcription in an in vitro setting. In this study, we have examined their cellular behaviour in detail and have shown that two of these compounds (ABA13 and ABA833) potently inhibit the proliferation of a range of human tumour cell lines, and show some specificity towards breast carcinoma cell lines. In most of the cell lines investigated, ABA833 was the more potent of the two compounds. Flow cytometric analysis revealed that ABA13 and ABA833 (50-500 nM) induced an S phase block and increased the pre-G1 population in MCF-7 and MDA 468 human breast cancer cells. An increase in the pre-G1 population of RKO colon carcinoma cells was seen only at 500 nM with ABA833, reflecting the reduced sensitivity of this cell line to the bis-benzimidazoles in comparison to the breast cancer cell lines. Mechanistic studies revealed that neither ABA13 or ABA833 act as topoisomerase I (topo I) or topoisomerase II (topo II) poisons in plasmid or kinetoplast DNA (kDNA) relaxation assays, but both compounds do inhibit the catalytic activity of these enzymes. Drug uptake studies showed that reduced sensitivity of MCF-7adr and RKO cells compared with MCF-7 to both ABA13 and ABA833 correlated with a markedly reduced intracellular drug accumulation.

Antineoplastic Agents↗
PubMed2003

Plant sterol-enriched spread enhances the cholesterol-lowering potential of a fat-reduced diet.

OBJECTIVE: To determine the effect of a plant sterol-enriched spread on plasma cholesterol concentrations when replacing butter or a standard polyunsaturated spread in a diet containing 30% of energy fat. DESIGN: Parallel butter phase followed by double-blind, randomized, cross-over polyunsaturated spread phases. SETTING: General community. SUBJECTS: Volunteer sample of 50 free-living men and women with mean age (s.d.) 46.7 y (10.5), moderately elevated plasma total cholesterol 5.95 mmol/l (0.78), and body mass index 26.0 (3.9) kg/m(2). INTERVENTION: Participants ate a moderately low-fat diet (30% of energy) for the 11-week intervention. During the first 3 weeks the diet included 20 g per day of butter. Participants were then randomized to replace the butter with 25 g of polyunsaturated spread with or without 2 g of plant sterols for 4 weeks, crossing over in the last 4 weeks to the alternate spread. MAIN OUTCOME MEASURES: Plasma cholesterol and fatty acids. RESULTS: Replacing butter with a standard polyunsaturated fat spread reduced mean plasma total cholesterol concentrations by 4.6% (from 6.09 (0.82) to 5.81 (0.77) mmol/l, P<0.01) and low-density lipoprotein cholesterol by 5.5% (from 3.98 (0.76) to 3.76 (0.74) mmol/l, P<0.05). Replacing butter with a polyunsaturated spread containing plant sterols reduced plasma total cholesterol by 8.9% (from 6.09 (0.82) to 5.55 (0.76) mmol/l, P<0.01) and low density lipoprotein cholesterol by 12.3% (from 3.98 (0.76) to 3.49 (0.72) mmol/l, P<0.01). Plasma high density lipoprotein cholesterol concentration was the same on the three diets. CONCLUSION: In people with moderately raised plasma cholesterol concentrations consuming reduced-fat diets the reduction in plasma total and low-density lipoprotein cholesterol concentrations achieved by replacing butter with a polyunsaturated spread is enhanced by addition of plant sterols.

Body Mass Index↗
PubMed2003

Angiotensin-I-converting enzyme insertion/deletion polymorphism and high urinary albumin concentration in French Type 2 diabetes patients.

AIMS: Family-based studies suggest a genetic basis for nephropathy in Type 2 diabetes. The angiotensin-I-converting enzyme (ACE) gene is a candidate gene for Type 1 diabetes nephropathy. We assessed the association between high urinary albumin concentration and ACE insertion/deletion (I/D) polymorphism, in French Type 2 diabetes patients. METHODS: We studied 3139 micro/macroalbuminuric French patients recruited in the DIABHYCAR Study, an ACE inhibition trial in Type 2 diabetes patients with renal and cardiovascular outcomes. The main inclusion criteria were age >/= 50 years, urinary albumin concentration >/= 20 mg/l assessed centrally during two consecutive screening visits, and plasma creatinine concentration </= 150 micro mol/l. These patients were compared with 605 normoalbuminuric (NA; urinary albumin concentration < 10 mg/l at first screening for the DIABHYCAR Study) French patients. ACE I/D genotype was determined by nested polymerase chain reaction. RESULTS: The ACE I/D polymorphism was in Hardy-Weinberg equilibrium. The distribution of genotypes did not differ significantly between micro/macroalbuminuric and NA patients: 552 and 115 II, 1468 and 282 ID, 1119 and 208 DD (P = 0.67). However, the ACE D allele was more frequent among normotensive micro/macroalbuminuric patients than among NA patients (P = 0.039). CONCLUSIONS: The ACE I/D polymorphism was not associated with high urinary albumin concentration in French Type 2 diabetes patients.

Aged↗
PubMed2003

Relation between body mass index and mortality in an unusually slim cohort.

STUDY OBJECTIVE: To investigate the relation between body mass index and mortality in an unusually slim cohort. DESIGN: Prospective cohort study. SETTING: United Kingdom. PARTICIPANTS: About 11,000 non-meat eaters and their meat eating friends and relatives, with a median age of 33 years were recruited between 1980 and 1984. More than 20% of the cohort had a self reported BMI below 20 kg/m(2) at recruitment. There were 195,000 person years of observation after a mean of 18.0 years of follow up. MAIN RESULTS: The characteristics of participants with a BMI below 18 kg/m(2) were favourable to a lower risk of cardiovascular disease. Nevertheless, these participants had an increased all cause death rate ratio (2.07, 95% CI 1.58 to 2.70) in comparison with participants who had a BMI between 20 and 22 kg/m(2). The death rate ratio for the slimmest category was also significantly increased for circulatory diseases (including ischaemic heart disease and cerebrovascular disease), respiratory diseases, and all other causes combined excluding all malignant neoplasms. This finding was consistent across a range of subgroups. CONCLUSIONS: Lean men and women (BMI <18 kg/m(2)) experience increased all cause mortality compared with those with a BMI between 20 and 22 kg/m(2). This pattern is not seen for cancer mortality, but is found for cardiovascular and respiratory diseases. It is important that public health messages regarding healthy eating are aimed at maintaining a healthy body weight rather than just "losing weight".

Adolescent↗
PubMed2003

[Oral health in dementia patients].

Dementia shares multiple clinical symptoms characterized by cognitive deficits that interfere with daily activities but differentiated by etiology. Advanced age is a major risk factor for dementia especially in more developed countries where older adults are most evident and growing rapidly. Since the prevalence of edentulism is decreasing, greater efforts will be necessary in the future to maintain oral health in dementia patients. Meeting the oral care needs of these individuals can be very challenging and should include prevention, maintenance of oral function and improved access for emergencies as well as regular dental care. Dental professionals should provide complex treatment utilizing appropriate behavioral and communication techniques. At the national level there is also a need for oral disease prevention programs directed towards staff, family members, and other caregivers of dementia patients.

Activities of Daily Living↗
PubMed2003

[Is there a need for an additional dental school in Israel? 2002 status and future forecasting].

Dental manpower planning is constantly in discussion throughout the world. Current data indicates a transition from oversupply reports 10 to 20 years ago to a present undersupply of dentists with a forecast for further shortage in the near future. The dental profession in Israel has gone through deep and extreme changes since the late 80'. Dentists are now at the "bottom of the barrel" and many abandoned the profession after long and demanding years of education. The future of the academic dental institutions is also unclear. In spite of the current unrealistic present, we are witnessing some processes that might change the status of the dental profession in Israel in the near future. Among these are the changing roll of female dentists in the profession, increasing age of practicing dentists, obligatory state licensing exams, less immigration of dentists and the natural growth of the population. Together with the expected increase of demand for dental care, a decrease in the number of dentists in Israel will result in a balanced dental manpower in 2011. Therefore, the necessity of establishing a third dental school in Israel was brought to discussion. Dental schools are responsible not only for students qualification as caregivers, but also for enrichment of practicing dentists with updated data, and qualifying specialist dentists in the various fields of the profession. At the present, there is no justification for establishing a third dental school in Israel. Nevertheless, it is obligatory to maintain and strengthen the two existing dental schools in spite of the needed high costs. Only in this way the profession will continue to enjoy a nation high quality professional and academic dental manpower. The continuous qualification of specialists will be maintained and an open "path" will be available for future manpower enlargement. Hastiness and rashness, which ended in national shortage of dentists in other countries, should be avoided in Israel.

Age Factors↗
PubMed2002

Predator-prey encounters in turbulent waters.

With reference to studies of predator-prey encounters in turbulent waters, we demonstrate the feasibility of an experimental method for investigations of particle fluxes to an absorbing surface in turbulent flows. A laboratory experiment is carried out, where an approximately homogeneous and isotropic turbulent flow is generated by two moving grids. The simultaneous trajectories of many small neutrally buoyant polystyrene particles are followed in time. Selecting one of these to represent a predator, while the others are considered as prey, we obtain estimates for the time variation of the statistical average of the prey flux into a suitably defined "sphere of interception." The variation of this flux with the radius in the sphere of interception, as well as the variation with basic flow parameters is well described by a simple model, in particular for radii smaller than a characteristic length scale for the turbulence. Also the Eulerian counterpart of the problem has been analyzed, and the particle fluxes from the two studies compared.

Journal Article↗
PubMed2001

[Renal failure and cardiovascular risk. Increased borderline serum creatinine--a warning sign?].

It is well-known that patients with terminal renal insufficiency are at increased risk for a future cardiovascular event. A relevant relationship also appears to apply to the early stages of renal insufficiency. The HOPE study has shown that the incidence of myocardial infarction, apoplexy and cardiovascular mortality in patients with incipient renal insufficiency is significantly raised. The study also found that the incidence of cardiovascular events is in direct proportion to the level of serum creatinine. Against this background, patients at risk can be readily identified. The HOPE study documents a considerable cardiovascular risk for patients with incipient renal insufficiency and concomitant uncomplicated hypertension, atherosclerosis or diabetes. In view of this, the use of ACE inhibitors in patients with moderate renal insufficiency should now be introduced. In the HOPE subjects, ramipril was found not only to lower the cardiovascular risk, but also to improve renal insufficiency.

Adult↗
PubMed2001

JunD regulates transcription of the tissue inhibitor of metalloproteinases-1 and interleukin-6 genes in activated hepatic stellate cells.

Activation of hepatic stellate cells (HSCs) to a myofibroblast-like phenotype is the pivotal event in hepatic wound healing and fibrosis. Rat HSCs activated in vitro express JunD, Fra2, and FosB as the predominant AP-1 DNA-binding proteins, and all three associate with an AP-1 sequence that is essential for activity of the tissue inhibitor of metalloproteinases-1 (TIMP-1) promoter. In this study, we used expression vectors for wild-type, dominant-negative, and forced homodimeric (Jun/eb1 chimeric factors) forms of JunD and other Fos and Jun proteins to determine the requirement for JunD in the transcriptional regulation of the TIMP-1 and interleukin-6 (IL-6) genes. JunD activity was required for TIMP-1 gene promoter activity, whereas overexpression of Fra2 or FosB caused a repression of promoter activity. The ability of homodimeric JunD/eb1 to elevate TIMP-1 promoter activity supports a role for JunD homodimers as the major AP-1-dependent transactivators of the TIMP-1 gene. IL-6 promoter activity was induced upon activation of HSCs and also required JunD activity; however, expression of JunD/eb1 homodimers resulted in transcriptional repression. Mutagenesis of the IL-6 promoter showed that an AP-1 DNA-binding site previously reported to be an activator of transcription in fibroblasts functions as a suppressor of promoter activity in HSCs. We conclude that JunD activates IL-6 gene transcription as a heterodimer and operates at an alternative DNA-binding site in the promoter. The relevance of these findings to events occurring in the injured liver was addressed by showing that AP-1 DNA-binding complexes are induced during HSC activation and contain JunD as the predominant Jun family protein. JunD is therefore an important transcriptional regulator of genes responsive to Jun homo- and heterodimers in activated HSCs.

Animals↗
PubMed2001

A new class of symmetric bisbenzimidazole-based DNA minor groove-binding agents showing antitumor activity.

The synthesis and evaluation of the novel head-to-head bisbenzimidazole compound 2,2-bis[4'-(3' '-dimethylamino-1' '-propyloxy)phenyl]-5,5-bi-1H-benzimidazole is described. An X-ray crystallographic study of a complex with the DNA dodecanucleotide sequence d(CGCGAATTCGCG) shows the compound bound in the A/T minor groove region of a B-DNA duplex and that the head-to-head bisbenzimidazole motif hydrogen-bonds to the edges of all four consecutive A:T base pairs. The compound showed potent growth inhibition with a mean IC(50) across an ovarian carcinoma cell line panel of 0.31 microM, with no significant cross-resistance in two acquired cisplatin-resistant cell lines and a low level of cross-resistance in the P-glycoprotein overexpressing acquired doxorubicin-resistant cell line. Studies with the hollow fiber assay and in vivo tumor xenografts showed some evidence of antitumor activity.

Animals↗
PubMed2001

Laboratory investigations of the survivability of bacteria in hypervelocity impacts.

It is now well established that material naturally moves around the Solar System, even from planetary surface to planetary surface. Accordingly, the idea that life is distributed throughout space and did not necessarily originate on the Earth but migrated here from elsewhere (Panspermia) is increasingly deemed worthy of consideration. If life arrived at the Earth from space, its relative speed will typically be of order many km s-1, and the resulting collision with the Earth and its atmosphere will be in the hypervelocity regime. A mechanism for the bacteria to survive such an impact is required. Therefore a programme of hypervelocity impacts in the laboratory at (4.5 +/- 0.6) km s-1 was carried out using bacteria (Rhodococcus) laden projectiles. After impacts on a variety of target materials (rock, glass and metal) attempts were made to culture Rhodococcus from the surface of the resulting craters and also from the target material ejected during crater formation. Control shots with clean projectiles yielded no evidence for Rhodococcus growth from any crater surface or ejecta. When projectiles doped with Rhodococcus were used no impact crater surface yielded colonies of Rhodococcus. However, for four shots of bacteria into rock (two on chalk and two on granite) the ejecta was afterwards found to give colonies of Rhodococcus. This was not true for shots onto glass. In addition, shots into aerogel (density 96 kg m-3) were also carried out (two with clean projectiles and two with projectiles with Rhodococcus). This crudely simulated aero-capture in a planetary atmosphere. No evidence for Rhodococcus growth was found from the projectiles captured in the aerogel from any of the four shots.

Earth, Planet↗