Biomedical subjects

B Lucas

Publications and source records attributed to B Lucas.

At least 37 records · Page 2Linked to original sources

PubMed2001

Maternal and child health nutrition training builds leadership skills.

For more than 30 years, the Maternal and Child Health Bureau (MCHB) has funded specialized professional training in nutrition with an emphasis on the development of leadership skills. A survey was conducted of individuals who received Maternal and Child Health nutrition training at the Center for Human Development and Disability (CHDD) at the University of Washington. Those surveyed were asked to reflect on the impact of the training on their career pathway and to report on their leadership activities. Of the 91 respondents, 83 (92%) indicated that the training supported a career pathway that emphasized maternal and child health or children with special healthcare needs. Eighty-five former trainees (93% of respondents) reported leadership activities at the local level, 61 (67%) reported leadership activities at the state level, and 46 (51%) reported leadership activities at the national level. The results of the survey indicate that specialized, intensive training in the field of nutrition develops and supports leadership skills.

Adult↗

PubMed2001

[Gastroduodenal metastases: an unusual manifestation of lung cancer. Study of two cases and review ot the literature].

INTRODUCTION: Diagnosis of gastroduodenal metastases is rare. Primary tumors are essentially melanomas and breast cancer, and exceptionally lung cancer. EXEGESIS: We report two patients who have a diagnosis of gastroduodenal metastases as initial manifestation of lung cancer. In one case, the patient died 3 weeks after the diagnosis. In the other case, chemotherapy was performed and complete response was obtained for the gastric metastasis. After a few months, node recurrence was diagnosed and the patient died 8 months after the diagnosis. CONCLUSION: We review the endoscopic and non-endoscopic literature and discuss the different histological types and therapeutic strategies concerning these unusual manifestations of lung cancer.

Abdominal Pain↗

PubMed2001

Sleep and brain lesions: a critical review of the literature and additional new cases.

We present a comprehensive review of sleep studies performed in patients with brain lesions complemented by 16 additional personal selected cases and by discussion of the corresponding animal data. The reader is cautioned about the risk of establishing an erroneous correlation between abnormal sleep and a given disorder due to the important inter and intra variability of sleep parameters among individuals. Salient points are stressed: the high frequency of post-stroke sleep breathing disorders is becoming increasingly recognised and may, in the near future, change the way this condition is managed. Meso-diencephalic bilateral infarcts induce a variable degree of damage to both waking and non-REM sleep networks producing and abnormal waking and sometimes a stage 1 hypersomnia reduced by modafinil or bromocriptine, which can be considered as a syndrome of cathecholaminergic deficiency. Central pontine lesions induce REM and non-REM sleep insomnia with bilateral lateral gaze paralysis. Bulbar stroke leads to frequent sleep breathing disorders. Polysomnography can help define the extent of involvement of various degenerative diseases. Fragmented sleep in Parkinson's disease may be preceded by REM sleep behavioural disorders. Multiple system atrophies are characterised by important sleep disorganization. Sleep waking disorganization and a specific ocular REM pattern are often seen in supra-nuclear ophtalmoplegia. In Alzheimer patients, sleep perturbations parallel the mental deterioration and are possibly related to cholinergic deficiency. Fronto-temporal dementia may be associated with an important decrease in REM sleep. Few narcoleptic syndromes are reported to be associated with a tumour of the third ventricle or a multiple sclerosis or to follow a brain trauma; all these cases raise the question whether this is a simple coincidence, a revelation of a latent narcolepsy or, as in non-DR16/DQ5 patients, a genuine symptomatic narcolepsy. Trypanosomiasis and the abnormal prion protein precociously after sleep patterns. Polysomnography is a precious tool for evaluating brain function provided it is realised under optimal conditions in stable patients and interpreted with caution. Several unpublished cases are presented: one case of pseudohypersomnia due to a bilateral thalamic infarct and corrected by modafinil, four probable late-onset autosomal recessive cerebellar ataxias without sleep pattern anomalies, six cases of fronto-temporal dementia with strong reduction in total sleep time and REMS percentage on the first polysomnographic night, one case of periodic hypersomnia associated with a Rathke's cleft cyst and four cases of suspected symptomatic narcolepsy with a DR16-DQ5 haplotype, three of which were post-traumatic without MRI anomalies, and one associated with multiple sclerosis exhibiting pontine hyper signals on MRI.

Animals↗

PubMed2001

A small molecule designed to bind to the adenine nucleotide pocket of Hsp90 causes Her2 degradation and the growth arrest and differentiation of breast cancer cells.

BACKGROUND: The Hsp90s contain a conserved pocket that binds ATP/ADP and plays an important role in the regulation of chaperone function. Occupancy of this pocket by several natural products (geldanamycin (GM) and radicicol) alters Hsp90 function and results in the degradation of a subset of proteins (i.e. steroid receptors, Her2, Raf). We have used the structural features of this pocket to design a small molecule inhibitor of Hsp90. RESULTS: The designed small molecule PU3 competes with GM for Hsp90 binding with a relative affinity of 15-20 microM. PU3 induces degradation of proteins, including Her2, in a manner similar to GM. Furthermore, PU3 inhibits the growth of breast cancer cells causing retinoblastoma protein hypophosphorylation, G1 arrest and differentiation. CONCLUSIONS: PU3 is representative of a novel class of synthetic compounds that binds to Hsp90 and inhibits the proliferation of cancer cells. These reagents could provide a new strategy for the treatment of cancers.

Adenine Nucleotides↗

PubMed2001

Multiple renal arteries do not pose an impediment to the routine use of laparoscopic donor nephrectomy.

UNLABELLED: Since the first description by Ratner and collegues in 1996, laparoscopic live-donor nephrectomy is gaining wide acceptance in an attempt to minimize the donor morbidity, length of hospital stay and length of time to return to work. It is unknown whether multiple renal arteries pose additional problems with laparoscopic donor nephrectomy. In November 1998, our institution initiated laparoscopic donor nephrectomy program. In the ensuing 19 months, we performed 25 living donor renal transplants, 24 of them using laparoscopic donor nephrectomy. The left kidney was procured in all cases. Eight donor candidates (33%) had two or more renal arteries (two arteries in five patients and three patients). RESULTS: In six cases (25%), findings at surgery differed from the CT angography results (in four cases, CT angiogram reported fewer arteries than were found at surgery and in two cases it reported more). We found no significant differences in both donor outcomes and recipient, based on the presence or absence of multiple renal arteries. Among donor outcomes, we found equivalent results for donor warm ischemia time total donor operating time, and donor length of stay. For recipient outcomes, we found no significant differences between groups for the incidence of acute tubular necrosis (ATN), graft survival and most recent serum creatinine. In one case, we constructed two arteries into a single conduit on the backtable prior to transplantation. However, in most cases with multiple arteries, we implanted the arteries separately into the recipient external iliac artery. Based on this experience, we do not find the presence of multiple renal arteries to be a barrier to the successful use of kidney grafts procured by laparoscopic donor nephrectomy.

Adult↗

PubMed2001

Prolactin receptor signal transduction pathways and actions determined in prolactin receptor knockout mice.

Prolactin-receptor-deficient mice are a good model in which to study the various actions of prolactin. Female homozygous knockout mice are completely infertile and show a lack of mammary development, while hemizogotes are unable to lactate following their first pregnancy. Male and female homozygotes have markedly elevated serum prolactin levels, and in some instances pituitary hyperplasia is present. Maternal behaviour is severely affected in both hemizygous and homozygous animals. Bone formation is reduced in young animals and in adults (males and females). Finally, older males and females show a slight reduction in body weight, which seems to be due to reduced abdominal fat deposition in the knockout animals.

Animals↗

PubMed2001

Adoptive transfer of CD4+ T cells specific for subunit A of Helicobacter pylori urease reduces H. pylori stomach colonization in mice in the absence of interleukin-4 (IL-4)/IL-13 receptor signaling.

Protection in the murine model of Helicobacter pylori infection may be mediated by CD4+ T cells, but the mechanism remains unclear. To better understand how protection occurs in this model, we generated and characterized H. pylori urease-specific CD4+ T cells from BALB/c mice immunized with Salmonella enterica serovar Typhimurium expressing H. pylori urease (subunits A and B). The CD4+ T cells were found to be specific for subunit A (UreA). Upon antigen-specific stimulation, expression of interleukin 4 (IL-4), IL-10, gamma interferon (IFN-gamma), and tumor necrosis factor alpha was induced. Immunocytochemical analysis showed that the majority of cells produced IFN-gamma and IL-10. Adoptive transfer of the UreA-specific CD4+ T cells into naive syngeneic recipients led to a threefold reduction in the number of bacteria in the recipient group when compared to that in the nonrecipient group. Stomach colonization was also reduced significantly after transfer of these cells into patently infected mice. Adoptive transfer of UreA-specific CD4+ T cells into IL-4 receptor alpha chain-deficient BALB/c mice indicated that IL-4 and IL-13 were not critical in the control of bacterial load. In addition, synthetic peptides were used to identify three functional T-cell epitopes present in subunit A which were recognized by the UreA-specific T cells. Analysis of H. pylori-specific cellular immune responses in recipient challenged and nonrecipient infected mice indicated a strong local restriction of the response in infected animals. The implications of these findings for the mechanism of protection and the development of peptide-based vaccination are discussed.

Adoptive Transfer↗

PubMed2001

Stance control is not affected by paresis and reflex hyperexcitability: the case of spastic patients.

OBJECTIVES: Spastic patients were studied to understand whether stance unsteadiness is associated with changes in the control of voluntary force, muscle tone, or reflex excitability, rather than to abnormal posture connected to the motor deficit itself. METHODS: Twenty four normal subjects, 12 patients affected by amyotrophic lateral sclerosis (ALS), seven by spastic paraparesis, and 14 by hemiparesis were studied. All patients featured various degrees of spasticity and paresis but were free from clinically evident sensory deficits. Body sway during quiet upright stance was assessed through a stabilometric platform under both eyes open (EO) and eyes closed (EC) conditions. The sudden rotation of a supporting platform, in a toe up and toe down direction respectively, evoked short (SLR) and medium latency (MLR) reflex responses to stretch of the soleus or the tibialis anterior (TA) muscle. RESULTS: No relation was found between clinical findings (tone, muscle strength, tendon reflexes, plantar response, and duration of disease) and body sway. On average, all patient groups exhibited a forward shift of the centre of foot pressure (CFP) with respect to normal subjects; in addition, paraparetic and to a much larger extent hemiparetic patients showed a lateral shift of CFP. Body sway area was significantly increased only in the hemiparetic patients. No relation was found between position of the CFP and sway within any patient group. Soleus SLR was increased in all patients with respect to normal subjects. TA SLR was often seen in both patients with ALS and paraparetic patients, but only rarely in normal subjects and hemiparetic patients. However, no relation was found between amplitude of soleus or TA SLRs and stabilometric variables. The frequency and size of soleus MLR and TA MLR were decreased in all patients. These responses were decreased in size and not modulated by background EMG in the affected leg of hemiparetic patients, suggesting a disturbed control of spinal reflexes fed by spindle group II afferent fibres. CONCLUSIONS: It is proposed that body posture, paresis, or monosynaptic reflex hyperexcitability do not affect the control of equilibrium during quiet upright stance. In hemiparetic patients, the decreased amplitude of MLRs might be the main cause of the large postural instability. The results are congruent with the hypothesis of a role for group II afferent input in the reflex control of equilibrium.

Adult↗

PubMed2001

Electrical and mechanical H(max)-to-M(max) ratio in power- and endurance-trained athletes.

The aim of this study was to compare the mechanical and electromyographic (EMG) characteristics of soleus motor units activated during maximal H reflex and direct M response among subjects with different histories of physical activity. Power-trained athletes produced stronger twitches, with a higher rate of twitch tension buildup and relaxation, than their endurance counterparts for both maximal H-reflex and maximal M-wave responses. The maximal H-reflex-to-maximal M-wave ratios for both force output (twitch) and EMG wave amplitude were significantly lower in power-trained than endurance-trained athletes. However, power-trained athletes exhibited a significantly greater twitch-to-EMG ratio for the reflexly activated motor units with respect to the entire motor pool, whereas endurance-trained athletes had comparable twitch-to-EMG ratios for both reflexly and directly activated units. Power training increases the force output of the whole ensemble of the motor units, thereby compensating for the lower efficacy of the reflex transmission between Ia spindle afferent input and soleus alpha-motoneuron. On the other hand, the lower level of force evoked by the reflexly activated units in endurance-trained athletes is associated with a greater motor pool reflex excitability. Therefore, endurance-trained athletes produce the necessary force by recruitment of more slow-twitch units than do other subjects for comparable levels of force and type of task.

Adult↗

PubMed2001

Costs and characteristics of heavy inpatient service users in outer London.

"Heavy users" is a new term often used to describe those who occupy a disproportionate number of psychiatric beds. In this study we identified the heaviest 10% (193) inpatient service users in one London borough over a 6 year period and compared these with a control group of 400 ordinary inpatient users. A weighting index was used to combine frequency of admission with duration. Heavy users were diagnostically and demographically similar to ordinary inpatient service users and only differed by their extensive use of services, about 3 times more than ordinary users in terms of health care costs, during the measured year. Their heavy use mainly depended on occupying hospital beds, and their use of outpatient, day patient and community services was relatively light.

Adult↗

PubMed2000

How CD4(+) T cells may eliminate extracellular gastric Helicobacter?

Helicobacter pylori is recognised as a causal agent in the pathogenesis of gastritis, gastric and duodenal ulcer disease as well as gastric cancers. Eradication of the bacteria with antibiotics is currently used to treat symptomatic, infected individuals. Theoretically the infection could also be controlled by vaccination. Several immunisation protocols were developed in small animal models and primates in order to validate this approach. Recently making use of mice with defined genetic defects, H. pylori-specific CD4(+) T cells were found to be crucial for protective vaccination. This was unexpected and poses the question of how activation of CD4(+) T cells leads to the elimination of bacteria that reside primarily in the mucin layer behind a barrier of epithelial cells. CD4(+) T cells fulfil their effector function by secreting lymphokines and by engaging specific surface ligands on interacting cells. Here we propose that phagocytes and epithelial cells stimulated either by direct interaction with CD4(+) T cells or by soluble mediators such as cytokines or neuropeptides are the ultimate effector populations in protective immunity induced by vaccination.

Animals↗

PubMed2000

TCR signaling for initiation and completion of thymocyte positive selection has distinct requirements for ligand quality and presenting cell type.

Thymocyte selection involves signaling by TCR engaging diverse self-peptide:MHC molecule ligands on various cell types in the cortex and medulla. Here we separately analyze early and late stages of selection to better understand how presenting cell type, ligand quality, and the timing of TCR signaling contribute to intrathymic differentiation. TCR transgenic CD4+CD8+ thymocytes (double positive (DP)) from MHC-deficient mice were stimulated using various presenting cells and ligands. The resulting CD69high cells were isolated and evaluated for maturation in reaggregate cultures with wild-type or MHC molecule-deficient thymic stroma with or without added hemopoietic dendritic cells (DC). Production of CD4+ T cells required TCR signaling in the reaggregates, indicating that transient recognition of self-ligands by DP is inadequate for full differentiation. DC bearing a potent agonist ligand could initiate positive selection, producing activated thymocytes that matured into agonist-responsive T cells in reaggregates lacking the same ligand. DC could also support the TCR signaling necessary for late maturation. These results argue that despite the negative role assigned to DC in past studies, neither the peptide:MHC molecule complexes present on DC nor any other signals provided by these cells stimulate only thymocyte death. These findings also indicate that unique epithelial ligands are not necessary for positive selection. They provide additional insight into the role of ligand quality in selection events and support the concept that following initiation of maturation from the DP state, persistent TCR signaling is characteristic of and perhaps required by T cells.

Animals↗

PubMed2000

Opening a window on thymic positive selection: developmental changes in the influence of cosignaling by integrins and CD28 on selection events induced by TCR engagement.

How TCR and non-TCR signals are integrated by thymocytes to generate a decision to undergo either positive or negative selection remains incompletely understood. Recent evidence suggests that TCR signal transduction changes its quality during thymocyte maturation, but whether the contributions of various cosignaling or costimulatory pathways to thymocyte selection also are modified during development is unclear. Questions also remain about the possible selective roles of specific costimulatory pathways in induction of differentiation vs death among thymocytes at any given stage of maturity. To address these issues, a quantitative in vitro analysis of initiation of CD4+CD8+ thymocyte differentiation as measured by CD69 up-regulation/coreceptor down-modulation was conducted in parallel with an analysis of induction of death. Using transfected cells varying in their surface display of ICAM-1 or B7.1 along with antibody blocking experiments, we demonstrate here that ICAM-1 provides a selective boost to signaling for differentiation without substantially affecting induction of death among CD4+CD8+ cells, a property that is lost as thymocytes mature further. In contrast, B7 engagement enhances both cell activation and death in parallel. Based on these data, we propose that the high level of ICAM-1 on cortical epithelial cells plays a special role in opening a window between TCR signaling for differentiation vs death, permitting efficient initiation of positive selection on epithelial ligands. In contrast, late CD28-dependent cosignaling on hemopoietic cells in the medulla would help enforce negative selection by augmenting the effects of TCR engagement by low levels of high affinity ligands.

Amino Acid Sequence↗

PubMed2000

Developmental regulation of TCR efficiency.

Unresponsiveness of mature T cells to the same self-peptide/self-MHC molecule complexes with which thymocytes have reacted during positive selection results from an increase of activation thresholds during maturation. The molecular events accounting for this increase are still unknown. In mature cells, a strong correlation between the extent of TCR down-modulation and T cell responses has been demonstrated. Exploiting this relationship, we show that the efficiency with which the TCR mediates full signaling is developmentally regulated. It decreases with thymic maturation and then increases with differentiation of naive T cells into memory lymphocytes. This analysis based on TCR modulation revealed an unexpected characteristic of the T cell receptor: its ability to signal fully is regulated inversely by its level of expression. This latter relationship may apply to other receptors both within and outside the immune system.

Animals↗

PubMed2000

Incidence of multiple sclerosis in Dijon, France: a population-based ascertainment.

Incidence of multiple sclerosis (MS) was prospectively determined within the population of the city of Dijon (94,000 inhabitants under 60 years old) at 47 degrees northern latitude, in Burgundy, France. All the incident cases were diagnosed according to the criteria of Poser, associated to the study of cerebrospinal fluid, evoked potentials and cerebral magnetic resonance imaging. Diagnosis was assessed in all the cases by a neurologist working either in the University Hospital (four neurologists) or in private offices (seven neurologists). The ascertainment was performed on a full 5-year period, from 1993 to 1997. Twenty-one cases were diagnosed in the population of 94,000 inhabitants, with an incidence of 6.1/100,000/year in women, 3.3/100,000/year in men and 4.3/100,000/year in both sexes. The sex-ratio female/male was 2.5. Our data are similar to those of the literature, in particular in countries around the Burgundy area. Our data allow evaluation of the burden of MS in our area and allow evaluation of the changes of incidence in the future.

Adolescent↗

PubMed2000

[Pyoderma gangrenosum and breast cancer: a new case].

We report here a new case of pyoderma gangrenosum (PG) associated with a breast cancer in a 39-year-old woman. We only found in literature three other reports of this rare entity which seems usually to be associated with monoclonal gammopathy, gastro-intestinal diseases such as Crohn's disease, chronic ulcerative colitis, leukemias or rheumatologic diseases. A commun hapten between of tumor and skin may explain the origin of this inflammatory lesion. In our case, PG could be a paraneoplastic syndrome.

Adult↗

PubMed2000

Continuous spikes and waves during slow sleep (CSWS): outcome in adulthood.

We report a longitudinal, electroencephalographic and neuropsychological analysis of epilepsy with continuous spikes and waves during slow sleep (CSWS) in a 19 year-old boy. The clinical course fluctuated, with temporary worsening or improvement of the paroxysmal abnormalities, epilepsy and cognitive functions. At the end of the follow-up period, seizures persisted. Evaluation of the boy's behaviour, language and cognitive function suggested a dysexecutive syndrome. We discuss the relationship between paroxysmal abnormalities and neuropsychological disorders.

Adult↗

PubMed2000

[Specific factors of diabetes in the rehabilitation of coronary patients].

This prospective controlled trial included two groups of subjects with coronary artery disease: one of 33 patients with non-insulin-dependent diabetes mellitus (6 females and 27 males, mean age 57 +/- 9 years, left ventricular ejection fraction of 56 +/- 14%) and the control group of 33 subjects without diabetes (3 females and 33 males, mean age of 57 +/- 11 years, LVEF of 58 +/- 11%). Before training heart rate was faster for patients with diabetes at rest (72 +/- 11 vs 66 +/- 81 bpm, p = 0.03) and at the end of the stress test (127 +/- 15 versus 118 +/- 18 bpm, p = 0.03). After rehabilitation, resting heart rate and peak heart rate were similar. However cardiovascular capacities improvement was better in subjects without diabetes mellitus, especially concerning peak VO2 (28.98 +/- 8.88 versus 22.78 +/- 6.28 mL/min/kg, p < 0.01) and mechanical power (138 +/- 48 versus 118 +/- 23 watts, p < 0.01). Two groups were retrospectively distinguished among diabetic patients: one group of 17 patients showing a VO2 improvement superior to 5% and a second group non improved (VO2 < 5%). For the second group the two selective factors were higher fasting glycemia (1.83 +/- 0.75 versus 1.31 +/- 0.38 g/L, p = 0.01) and higher hemoglobin A1C (8.05 +/- 2.04 vs 6.62 +/- 1.03%, p = 0.02). Heart rate variability was not significantly different for these two groups: changes in autonomic nervous system cannot explain resistance of diabetic subjects to training. On the other hand, principal aim must be the equilibrium of glycemia in the management of diabetes.

Aged↗