Search PubMed⌕ Search

Biomedical subjects

R Klein

Publications and source records attributed to R Klein.

At least 37 records · Page 2Linked to original sources
PubMed2002

Natrialba magadii virus phiCh1: first complete nucleotide sequence and functional organization of a virus infecting a haloalkaliphilic archaeon.

The double-stranded (ds)DNA virus phiCh1 infects the haloalkaliphilic archaeon Natrialba magadii. The complete DNA sequence of 58 498 bp of the temperate virus was established, and the probable functions of 21 of 98 phiCh1-encoded open reading frames (ORFs) have been assigned. This knowledge has been used to propose functional modules each required for specific functions during virus development. The phiCh1 DNA is terminally redundant and circularly permuted and therefore appears to be packaged by the so-called headful mechanism. The presence of ORFs encoding homologues of proteins involved in plasmid replication as well as experimental evidence indicate a plasmid-mediated replication strategy of the virus. Results from nanosequencing of virion components suggest covalent cross-linking of monomers of at least one of the structural proteins during virus maturation. A comparison of the phiCh1 genome with the partly sequenced genome of Halobacterium salinarum virus phiH revealed a close relationship between the two viruses, although their host organisms live in distinct environments with respect to the different pH values required for growth.

Base Sequence↗
PubMed2002

Relation of ocular trauma to cortical, nuclear, and posterior subcapsular cataracts: the Beaver Dam Eye Study.

BACKGROUND: The consequences of minor ocular trauma in the general population are unclear. The relation of self reported ocular trauma to cortical, nuclear, and posterior subcapsular cataracts is described in a defined population. METHODS: Population based, cross sectional study involving all people aged 43 to 86 years, living in Beaver Dam, Wisconsin (n=4926). Ocular trauma was ascertained by interview and cataract was graded from lens photographs. The relation of ocular trauma to cortical, nuclear, and posterior subcapsular cataracts was examined. RESULTS: People with a history of ocular trauma were more likely to have cortical (odds ratio (OR): 1.5; 95% confidence interval (CI): 1.0 to 2.2) and posterior subcapsular (OR: 1.7; 95% CI: 1.0 to 3.1) cataracts, compared to people without a history of trauma. These associations were stronger for people with previous trauma caused by a blunt object (OR: 3.3; 95% CI: 1.6 to 6.9 for cortical cataract, and OR: 4.1; 95% CI: 1.5 to 10.8 for posterior subcapsular cataracts). However, in analyses comparing the frequencies of cataract between traumatised and non-traumatised eyes among people with unilateral ocular trauma, the ocular trauma association for cortical cataract was no longer present, although the association for posterior subcapsular cataract persisted (OR: 2.4; 95% CI: 0.8 to 7.8). CONCLUSION: The data provide evidence of a possible association between self reported ocular trauma and posterior subcapsular cataract.

Adult↗
PubMed2002

Retinal microvascular abnormalities and blood pressure in older people: the Cardiovascular Health Study.

AIM: To examine the relation between blood pressure and retinal microvascular abnormalities in older people. METHODS: The Cardiovascular Health Study is a prospective cohort study conducted in four US communities initiated in 1989 to 1990. Blood pressure was measured according to standardised protocols at each examination. During the 1997-8 examination, retinal photographs were taken of 2405 people aged 69-97 years (2056 without diabetes and 349 with diabetes). Signs of focal microvascular abnormalities (focal arteriolar narrowing, arteriovenous nicking, and retinopathy) were evaluated from photographs according to standardised methods. To quantify generalised arteriolar narrowing, the photographs were digitised and diameters of individual arterioles were measured and summarised. RESULTS: In non-diabetic people, elevated concurrent blood pressure taken at the time of retinal photography was strongly associated with presence of all retinal microvascular lesions. The multivariable adjusted odds ratios, comparing the highest to lowest quintile of concurrent systolic blood pressure, were 4.0 (95% confidence intervals (CI): 2.4 to 6.9, p test of trend<0.001) for focal arteriolar narrowing, 2.9 (95% CI: 1.6 to 5.3, p<0.001) for arteriovenous nicking, 2.8 (95% CI: 1.5 to 5.2, p<0.001) for retinopathy, and 2.1 (95% CI: 1.4 to 3.1, p<0.001) for generalised arteriolar narrowing. Generalised arteriolar narrowing and possibly arteriovenous nicking were also significantly associated with past blood pressure measured up to 8 years before retinal photography, even after adjustment for concurrent blood pressure. These associations were somewhat weaker in people with diabetes. CONCLUSIONS: Retinal microvascular abnormalities are related to elevated concurrent blood pressure in older people. Additionally, generalised retinal arteriolar narrowing and possibly arteriovenous nicking are related to previously elevated blood pressure, independent of concurrent blood pressure. These data suggest that retinal microvascular changes reflect severity and duration of hypertension.

Aged↗
PubMed2002

Is there stimulant sensitivity in children?

It has been suggested that exposure to stimulants alters the dopamine system and thus enhances sensitivity to stimulants and possibly other drugs. Sensitization has been induced experimentally in animals, especially in rats, and has been shown to be long-lasting. In addition, cross-sensitization across different compounds has been demonstrated. The animal data have raised concern that exposure to methylphenidate in childhood may enhance the risk for later abuse of stimulants and other drugs. We review the evidence bearing on sensitization in children treated with stimulants and followed into adulthood. None of four clinic-based studies found an excess of drug abuse in children previously treated with stimulants. A school-based longitudinal study obtained a relationship between early stimulant treatment and later drug use, without controlling for dinical confounds. The single prospective-controlled study of children who received placebo or methylphenidate does not support the sensitization hypothesis.

Adolescent↗
PubMed2002

Guidelines and algorithms for the use of methylphenidate in children with Attention-Deficit/ Hyperactivity Disorder.

OBJECTIVE: To review published algorithms for guiding the use of methylphenidate (MPH) in the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) in children and adolescents. METHODS: A consensus roundtable of 12 experts was convened to review the evidence for the safety and efficacy of MPH in the treatment of ADHD, as well as the published algorithms and practice guidelines for using MPH. The experts reviewed the algorithms for practicality and acceptability by clinicians. RESULTS: Algorithms that included MPH commonly selected it as the initial medication to be employed in the treatment of children with ADHD. Factors involved included its high efficacy, good safety record, and the ubiquitous nature of its appearance in the ADHD treatment literature. CONCLUSIONS: MPH should be considered as the first medication to be used in a treatment algorithm for children and adolescents with ADHD.

Adolescent↗
PubMed2001

Kinase-independent requirement of EphB2 receptors in hippocampal synaptic plasticity.

During development, Eph receptors mediate the repulsive axon guidance function of ephrins, a family of membrane attached ligands with their own receptor-like signaling potential. In cultured glutamatergic neurons, EphB2 receptors were recently shown to associate with NMDA receptors at synaptic sites and were suggested to play a role in synaptogenesis. Here we show that Eph receptor stimulation in cultured neurons modulates signaling pathways implicated in synaptic plasticity, suggesting cross-talk with NMDA receptor-activated pathways. Mice lacking EphB2 have normal hippocampal synapse morphology, but display defects in synaptic plasticity. In EphB2(-/-) hippocampal slices, protein synthesis-dependent long-term potentiation (LTP) was impaired, and two forms of synaptic depression were completely extinguished. Interestingly, targeted expression of a carboxy-terminally truncated form of EphB2 rescued the EphB2 null phenotype, indicating that EphB2 kinase signaling is not required for these EphB2-mediated functions.

Age Factors↗
PubMed2001

Retinal microvascular abnormalities and incident stroke: the Atherosclerosis Risk in Communities Study.

BACKGROUND: Retinal microvascular abnormalities reflect damage from hypertension and other vascular processes. We examined the relation of such abnormalities to incident stroke. METHODS: A cohort of 10358 men and women (aged 51 to 72 years) living in four US communities underwent retinal photography and standard grading for retinal microvascular abnormalities. The calibres of all retinal arterioles and venules were measured after digital conversion of the photographs, and a summary arteriole-to-venule ratio (AVR) was calculated as an index of arteriolar narrowing (smaller AVR indicates greater narrowing). Cases of incident stroke admitted to hospital were identified and validated by case record reviews. FINDINGS: Over an average of 3.5 years, 110 participants had incident strokes. After adjustment for age, sex, race, 6-year mean arterial blood pressure, diabetes, and other stroke risk factors, most retinal microvascular characteristics were predictive of incident stroke, with adjusted relative risks of 2.58 (1.59-4.20) for any retinopathy, 3.11 (1.71-5.65) for microaneurysms, 3.08 (1.42-6.68) for soft exudates, 2.55 (1.27-5.14) for blot haemorrhages, 2.26 (1.00-5.12) for flame-shaped haemorrhages, and 1.60 (1.03-2.47) for arteriovenous nicking. The relative risk of stroke increased with decreasing AVR (p=0.03). The associations were similar for ischaemic strokes specifically, and for strokes in individuals with hypertension, either with or without diabetes. INTERPRETATION: Retinal microvascular abnormalities are related to incident stroke. The findings support a microvascular role in the pathogenesis of stroke. They suggest that retinal photography may be useful for cerebrovascular-risk stratification in appropriate populations.

Arteriosclerosis↗
PubMed2001

Hospital inquiries. No quick fix.

The Bristol inquiry highlights the disjunction between ends and means in the NHS. It draws attention to the 'make do and mend' culture in the service. The ethos of 'getting by' is seen as the enemy of excellence. Its most radical theme is the separation of management and regulation.

Cardiac Surgical Procedures↗
PubMed2001

Beta1-class integrins regulate the development of laminae and folia in the cerebral and cerebellar cortex.

Mice that lack all beta1-class integrins in neurons and glia die prematurely after birth with severe brain malformations. Cortical hemispheres and cerebellar folia fuse, and cortical laminae are perturbed. These defects result from disorganization of the cortical marginal zone, where beta1-class integrins regulate glial endfeet anchorage, meningeal basement membrane remodeling, and formation of the Cajal-Retzius cell layer. Surprisingly, beta1-class integrins are not essential for neuron-glia interactions and neuronal migration during corticogenesis. The phenotype of the beta1-deficient mice resembles pathological changes observed in human cortical dysplasias, suggesting that defective integrin-mediated signal transduction contributes to the development of some of these diseases.

Animals↗
PubMed2001

Risk of incident age-related eye diseases in people with an affected sibling : The Beaver Dam Eye Study.

The purpose of this investigation was to determine whether age-related cataract and maculopathy in older siblings predicts development of the same in younger siblings. A population-based study of age-related eye diseases was conducted in 1988--1990 in Beaver Dam, Wisconsin, and a follow-up examination was performed 5 years later. Diagnoses of age-related eye diseases were assigned on the basis of gradings of study photographs. There were 1,088 people from 488 sibships with at least two siblings who could contribute information for these analyses. The authors computed odds ratios and 95% confidence intervals for developing the specific lesion and identifying it 5 years later if an older sibling had it at baseline. The odds ratios were 1.65 (95% confidence interval (CI): 0.91, 2.99) for nuclear cataract, 1.62 (95% CI: 0.92, 2.85) for cortical cataract, 1.95 (95% CI: 0.48, 7.95) for posterior subcapsular cataract, 1.82 (95% CI: 0.91, 3.66) for soft drusen, 8.18 (95% CI: 3.34, 20.08) for retinal pigment epithelium depigmentation, 3.59 (95% CI: 1.71, 7.57) for increased retinal pigment, and 10.32 (95% CI: 0.83, 128.58) for exudative age-related maculopathy. These findings suggest that strong family determinants of lesions of age-related maculopathy are likely, less so for age-related cataract, which confer risk of the same lesion in a younger sibling.

Adult↗
PubMed2001

Temperature development in a modern municipal solid waste incineration (MSWI) bottom ash landfill with regard to sustainable waste management.

Municipal solid waste is treated in incineration plants to reduce the volume, the toxicity and the reactivity of the waste. The final product, municipal solid waste incineration (MSWI) bottom ash, was considered as a material with a low reactivity, which can safely be deposited in a MSWI bottom ash landfill, or which can be used, e.g. in road construction after further treatment. However, temperature measurements in MSWI bottom ash landfills showed temperatures up to 90 degrees C, caused by exothermic reactions within the landfill. Such high temperatures may affect the stability of the flexible polymer membrane liner (FML) and may also lead to an accelerated desiccation of the clay barrier. At the beginning of this study it was uncertain whether those reported results would be applicable to modern landfills, because the treatment techniques in MSWI and landfills have changed, bottom and fly ash are stored separately, and the composition of the incinerated waste has changed significantly since the publication of those results. The aim of this study was to gain detailed knowledge of temperature development under standard disposal conditions in relation to the rate of ash disposal, the variation of layer thickness, and the environmental conditions in a modern landfill. Temperatures were measured at nine levels within the body of a landfill for a period of nearly 3 years. Within 7 months of the start of the disposal, a temperature increase of up to 70 degrees C within the vertical centre of the disposal was observed. In the upper and central part of the landfill this initial temperature increase was succeeded by a decrease in temperature. The maximum temperature at the time of writing (May 2000) is about 55 degrees C in the central part of the landfill. The maximum temperature (45.9 degrees C) at the FML was reached 17 months after the start of the deposition. Since then the temperatures decreased at a rate of 0.6 degrees C per month. Temperature variation within each individual layer corresponds to the temperature of the underlying layer and the overall surface-to-volume ratio of the landfill. The temperatures in the uppermost layer are significantly influenced by the ambient temperatures.

Cities↗
PubMed2001

Ephrin-B3 is the midline barrier that prevents corticospinal tract axons from recrossing, allowing for unilateral motor control.

Growing axons follow highly stereotypical pathways, guided by a variety of attractive and repulsive cues, before establishing specific connections with distant targets. A particularly well-known example that illustrates the complexity of axonal migration pathways involves the axonal projections of motor neurons located in the motor cortex. These projections take a complex route during which they first cross the midline, then form the corticospinal tract, and ultimately connect with motor neurons in the contralateral side of the spinal cord. These obligatory contralateral connections account for why one side of the brain controls movement on the opposing side of the body. The netrins and slits provide well-known midline signals that regulate axonal crossings at the midline. Herein we report that a member of the ephrin family, ephrin-B3, also plays a key role at the midline to regulate axonal crossing. In particular, we show that ephrin-B3 acts as the midline barrier that prevents corticospinal tract projections from recrossing when they enter the spinal gray matter. We report that in ephrin-B3(-/-) mice, corticospinal tract projections freely recross in the spinal gray matter, such that the motor cortex on one side of the brain now provides bilateral input to the spinal cord. This neuroanatomical abnormality in ephrin-B3(-/-) mice correlates with loss of unilateral motor control, yielding mice that simultaneously move their right and left limbs and thus have a peculiar hopping gait quite unlike the alternate step gait displayed by normal mice. The corticospinal and walking defects in ephrin-B3(-/-) mice resemble those recently reported for mice lacking the EphA4 receptor, which binds ephrin-B3 as well as other ephrins, suggesting that the binding of EphA4-bearing axonal processes to ephrin-B3 at the midline provides the repulsive signal that prevents corticospinal tract projections from recrossing the midline in the developing spinal cord.

Animals↗
PubMed2001

Design and synthesis of inhibitors of adenosine and AMP deaminases.

Nucleosides and nucleotides which are able to undergo covalent hydration in the aglycone ring system are potential inhibitors of the enzymes adenosine deaminase (ADA) and AMP deaminase, respectively. Calculations of the enthalpy of covalent hydration and of enzyme binding energy have been used to design new inhibitors of ADA. The ribosyl triazolotriazine 16, which was synthesized as a result of these calculations, exists predominantly as the covalent hydrate 18 in water and is a potent inhibitor of mammalian ADA (IC(50) 50 nM).

AMP Deaminase↗