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Biomedical subjects

K David

Publications and source records attributed to K David.

At least 19 recordsLinked to original sources

Reduction of Escherichia coli adherence to uroepithelial bladder cells after consumption of cranberry juice: a double-blind randomized placebo-controlled cross-over trial.

To determine the efficacy of the consumption of cranberry juice versus placebo with regard to the presence of in vitro bacterial anti-adherence activity in the urine of healthy volunteers. Twenty healthy volunteers, 10 men and 10 women, were included. The study was a double-blind, randomized, placebo-controlled, and cross-over study. In addition to normal diet, each volunteer received at dinner a single dose of 750 ml of a total drink composed of: (1) 250 ml of the placebo and 500 ml of mineral water, or (2) 750 ml of the placebo, or (3) 250 ml of the cranberry juice and 500 ml of mineral water, or (4) 750 ml of the cranberry juice. Each volunteer took the four regimens successively in a randomly order, with a washout period of at least 6 days between every change in regimen. The first urine of the morning following cranberry or placebo consumption was collected and used to support bacterial growth. Six uropathogenic Escherichia coli strains (all expressing type 1 pili; three positive for the gene marker for P-fimbriae papC and three negative for papC), previously isolated from patients with symptomatic urinary tract infections, were grown in urine samples and tested for their ability to adhere to the T24 bladder cell line in vitro. There were no significant differences in the pH or specific gravity between the urine samples collected after cranberry or placebo consumption. We observed a dose dependent significant decrease in bacterial adherence associated with cranberry consumption. Adherence inhibition was observed independently from the presence of genes encoding type P pili and antibiotic resistance phenotypes. Cranberry juice consumption provides significant anti-adherence activity against different E. coli uropathogenic strains in the urine compared with placebo.

Adult↗

[Active ageing and quality of life--Results of a WHO demonstration project].

Based on the Active Ageing Programme of the World Health Organization (WHO), a demonstration project was conducted in a city in North-Rhine Westphalia between October 2002 and December 2004. The aim of the study was to promote an active ageing process, to maintain autonomy and independence among older people, and thereby to promote health and quality of life. The target group included people aged 55 to 80 years. The aim was to include older persons in a critical period of life due to loss of partner within the last five years and people undergoing a status change due to retirement within the last two years. 344 participants were visited at home to assess their health and psychosocial situation and to identify opportunities for activities. Participants were supported in their efforts to realise the agreed-upon activities. In this article results of the external evaluation are presented. It is analysed whether quality of life according to the WHOQOL Bref improves among participants in the course of the project. Results of non-parametric tests show small differences in quality of life between the three waves of interviews (at the beginning of the project, after one year, at the end of the project). This holds true when only those participants are analysed who retired within the last two years. However, quality of life significantly improves among older persons who lost their partner within the last five years. In terms of implementation of the WHO Active Ageing Programme results suggest application of a risk group strategy.

Adaptation, Psychological↗

Daclizumab is associated with decreased rejection and no increased mortality in cardiac transplant patients receiving MMF, cyclosporine, and corticosteroids.

BACKGROUND: Sparse published data exist on outcomes in daclizumab-treated cardiac transplant patients. One trial observed an increased mortality risk 6 and 12 months posttransplant in patients receiving daclizumab plus mycophenolate mofetil (MMF), cyclosporine, and steroids. This study further investigates the safety profile of daclizumab with this same immunosuppressive regimen from a large registry. METHODS: Data obtained at hospital discharge on all adult cardiac transplants performed in the USA between January 1998 and October 2003 for patients receiving MMF plus cyclosporine and steroids were accessed from the Scientific Registry of Transplant Recipients. Patients were selected based on induction treatment: daclizumab (n = 684) or no induction (n = 2525). Outcomes were evaluated at 6 months, 12 months, and 3 years posttransplant. Univariate Kaplan-Meier and multivariate Cox models were used to evaluate the effect of treatment on outcomes. Patient survival and infectious death were the primary endpoints. Secondary endpoints included rejection within the first year posttransplant (acute rejection; AR) and total rejection episodes over time. The two treatment groups shared similar demographics and transplant procedure details. RESULTS: Daclizumab (vs no induction) patients had no increased risk of patient death nor infectious death. Daclizumab patients had a lower incidence of AR at 6 months (P = .005) and 12 months (P < .001); the adjusted risk for AR at 12 months (hazards ratio [HR] = 0.77; P = .89) and over 3 years (HR 0.83, P = .006) was also lower in daclizumab-treated patients. CONCLUSIONS: In cardiac transplant patients, daclizumab (vs no induction) does not result in increased mortality or infectious death, and is associated with a lower incidence of AR.

Adult↗

[An atypical Demons-Meigs syndrome].

Meigs'syndrome is defined as a hydrothorax with ascites and benign ovarian tumor, both of which resolve on removal of the tumor. Pseudo-Meigs'syndrome or atypical Meigs'syndrome occurs when a pelvic mass other than an ovarian fibroma is present with hydrothorax and ascites. Both these syndromes should be nevertheless considered in women who present hydrothorax and ascites. This case concerns a 50-year-old woman who presented a pseudo-Meigs'syndrome (Hydrothorax and uterine leiomyoma). The distinction between these two syndrome is useless, because tumour removal is the only treatment.

Ascites↗

How reliable are light traps in estimating biting rates of adult Anopheles gambiae s.l. (Diptera: Culicidae) in the presence of treated bed nets?

The sampling efficiency of light trap catches relative to human bait catches in estimating biting rates of the mosquito Anopheles gambiae Giles was investigated in two types of community in southern Sierra Leone: (i) where most of the inhabitants slept under treated bed nets; and (ii) where most of the inhabitants slept without bed nets. The number of female A. gambiae mosquitoes caught in these communities by light trap was strongly correlated (r > or = 0.72) with those from corresponding human biting catches performed either on the same or adjacent nights. It was found that the relative sampling efficiency of light traps varied slightly but significantly with mosquito abundance in villages with treated bed nets, but not in those without them. Nevertheless, the relationship between relative sampling efficiency and mosquito abundance did not differ significantly between the two types of village. Overall, there was insufficient evidence to show that the presence of treated nets altered the relative efficiency of light traps and any bias was only slight, and unlikely to be of any practical importance. Hence, it was concluded that light traps can be used as a surrogate for human bait catches in estimating biting rates of A. gambiae mosquitoes in the two communities.

Animals↗

Conformational dynamics underlie the activity of the auxin-binding protein, Nt-abp1.

The auxin-binding protein 1 (ABP1) has been proposed to be involved in the perception of the phytohormone at the plasma membrane. Site-directed mutagenesis was performed on highly conserved residues at the C terminus of ABP1 to investigate their relative importance in protein folding and activation of a functional response at the plasma membrane. Detailed analysis of the dynamic interaction of the wild-type ABP1 and mutated proteins with three distinct monoclonal antibodies recognizing conformation-dependent epitopes was performed by surface plasmon resonance. The influence of auxin on these interactions was also investigated. The Cys(177) as well as Asp(175) and Glu(176) were identified as critical residues for ABP1 folding and action at the plasma membrane. On the contrary, the C-terminal KDEL sequence was demonstrated not to be essential for auxin binding, interaction with the plasma membrane, or activation of the transduction cascade although it does appear to be involved in the stability of ABP1. Taken together, the results confirmed that ABP1 conformational change is the critical step for initiating the signal from the plasma membrane.

Amino Acid Sequence↗

What establishes a protein as an allergen?

There is little known about the factors that determine the allergenicity of food proteins. Apparently, the ability of a food protein to induce an allergic response requires its presence in substantial amounts in the food supply, its durability during food processing, and its resistance to digestion in the gastrointestinal tract. In addition to the mode and degree of exposure, structural characteristics appear to play an important role for the capacity of a protein to modulate the immune response towards allergic reactions. Until now, however, there has been no indication for common structural characteristics of linear T cell or linear IgE (B cell) epitopes and the knowledge of structural characteristics of conformational IgE binding sites is very limited. Experimental data point only to certain surface areas of allergenic proteins which are important for IgE binding. Therefore, it is not possible to suggest any structural motif or conformational sequence pattern common to all allergenic proteins. Furthermore, glycosylation appears not to be a common critical determinant of allergenicity since food allergens comprise both glycoproteins and nonglycosylated proteins. Based on the few published three-dimensional structures of allergenic proteins including food proteins, one unifying feature of allergens appears to be their spherical shape. The three-dimensional structures of many more allergens have to be determined, however, to allow for a better understanding of the molecular basis of allergenicity. Most recently, new ideas have been introduced as to why certain biochemical or biologic functions such as enzymatic activities may predispose a protein to become an allergen. Proteolytically active allergens have been demonstrated to irritate the human mucosal surface, to enhance their own transmucosal uptake, and to augment IgE production. Therefore, the functional activity of some allergens may play a role among other factors in the process of sensitization and allergic responses.

Allergens↗

A novel metastatic animal model reflecting the clinical appearance of human neuroblastoma: growth arrest of orthotopic tumors by natural, cytotoxic human immunoglobulin M antibodies.

Neuroblastoma (NB), the most common extracranial solid tumor in childhood is associated with poor prognosis in patients with advanced tumor stages. Natural human cytotoxic anti-NB IgM antibodies present in the serum of healthy humans are discussed as a potential novel immunotherapeutic regimen against human NB because these antibodies have been shown to affect growth arrest of solid s.c. xenografts of human NB in nude rats. Subcutaneously induced tumors, however, exhibit a different growth pattern compared with the typical growth pattern of NB tumors in humans. Therefore, we developed in this study a novel metastatic tumor model in nude rats that reflects the clinical appearance of human NB and used this model to study the therapeutic efficacy of human anti-NB IgM. Intra-aortal injection of human NB cells in nude rats resulted in the development of large invasive adrenal gland tumors and micrometastases in the liver and bones. Apparently, adrenal glands provide most favorable growth conditions for human NB cells, as documented by the preferential and rapid growth of NB cells in this location. We studied three different treatment protocols of natural human anti-NB IgM. Anti-NB IgM completely inhibited tumor formation and metastases when injected simultaneously with human LAN-1 NB cells (P < 0.05). When antibody treatment was started 6 days after tumor cell injection (i.e., micrometastatic stage), tumor growth was inhibited by 90% (P < 0.05). An anti-NB IgM therapy directed against established tumors (14 days after tumor cell injection) shrank adrenal gland tumors by 90% (P < 0.05). Analysis of the tumors revealed both complement activation and an induction of apoptosis as two independent mechanisms of antitumor function. This study strongly suggests human anti-NB IgM antibodies as new agents for the therapy of neuroblastoma.

Adrenal Gland Neoplasms↗

Initial characterization of the apoptosis-inducing receptor for natural human anti-neuroblastoma IgM.

BACKGROUND: Human neuroblastoma (NB) cells contain a 260 kDa surface antigen (NB-p260), which serves as receptor for natural human IgM antibodies (anti-NB IgM). Upon binding to NB-p260, these antibodies induce apoptosis in human NB cells. PROCEDURE AND RESULTS: In this study, we purified NB-p260 to homogeneity from human LA-N-1 NB cells by sequential ion exchange chromatography followed by preparative SDS gel electrophoresis. Purified NB-p260 exhibited rapid autodegradation despite the presence of various protease inhibitors. The autodegradation process precluded extensive N-terminal sequencing. However, from repeat N-terminal sequence analysis, a consensus sequence of seven amino acid residues emerged that exhibited significant homology to the subunit c of the human mitochondrial ATP synthase, a hydrophobic membrane protein of 7.6 kDa. Western blot analyses demonstrated that purified NB-p260 was recognized by polyclonal antibodies raised against both subunit c-containing storage bodies and a synthetic peptide consisting of amino acid residues 32-45 of subunit c. In addition to peptide sequences related to subunit c, NB-p260 also contained epitopes related to the human heat shock protein HSP90. In Western blots, a monoclonal anti-HSP90 antibody reacted with purified NB-p260 as well as with a predominant protein fragment of approximately 90 kDa that appeared during the process of NB-p260 autodegradation. The anti-HSP90 antibody was also capable of binding to the surface of LA-N-1 cells and inhibiting the binding of human anti-NB IgM in a dose-dependent manner. CONCLUSIONS: Collectively, our data suggest that NB-p260, the apoptosis-mediating receptor for natural human anti-NB IgM, represents a novel surface protein of human NB cells containing polypeptide sequences related to the subunit c of the mitochondrial ATP synthase and the heat shock protein HSP90.

Animals↗

Detection of precytopathic effect of enteroviruses in clinical specimens by centrifugation-enhanced antigen detection.

Rapid enterovirus detection is important for decisions about antibiotic administration and length of hospital stay. The efficacy of rapid antigen detection-cell culture amplification (Ag-CCA) was evaluated with monoclonal antibodies (MAbs) 5-D8/1 (DAKO) and Pan-Enterovirus clone 2E11 (Chemicon) with 10 poliovirus, echovirus, and coxsackievirus type A and B stock isolates and College of American Pathologists check samples. By using Ag-CCA technology, MAb 2E11 was more sensitive than 5-D8/1 at detecting a greater number of stock isolates at or past tube (cytopathic effect [CPE]) culture (TC) end points. The efficacy of Ag-CCA in the clinical setting was subsequently confirmed with 273 consecutively freshly collected nasopharyngeal aspirate or swab specimens, rectal swab, and cerebrospinal fluid specimens during the 1999 enterovirus season. All specimens were tested by Ag-CCA in parallel with rhesus monkey kidney (RhMk), MRC-5, and A549 conventional TCs. Approximately 60% of field specimens were additionally tested with Hep-2 and HNK conventional TCs. Sixty-two percent of the clinical specimens tested were Ag-CCA positive after 48 h. Among 51 isolates, the mean time to CPE or culture confirmation was 5.5 days (range, 2 to 18 days). After 48 h, Ag-CCA achieved sensitivity, specificity, and positive and negative predictive values of 62, 100, 100, and 93%, respectively. During the same period, TC-CPE displayed test parameters of 12, 100, 100, and 85%, respectively. After 5 days, the sensitivity and specificity of Ag-CCA increased to 92 and 98%, respectively. Within the same period, isolation attained sensitivity and specificity of 52 and 100%, respectively. Although Ag-CCA displayed slightly reduced sensitivity and reduced specificity compared with conventional cell culture after 14 days, the markedly superior 48-h enterovirus Ag-CCA detection rate supports incorporation of this assay into the routine clinical setting.

Animals↗

Intervening to reduce weight gain in pregnancy and gestational diabetes mellitus in Cree communities: an evaluation.

BACKGROUND: A high prevalence of gestational diabetes mellitus and type 2 diabetes has been observed among the Cree of James Bay, Quebec. To address this problem, a diet and activity intervention during pregnancy, which was based on social learning theory, was initiated in 4 Cree communities. METHODS: A prospective intervention compared dietary, weight and glycemic indicators for 107 control subjects and for 112 women who received the intervention during the course of their pregnancy. A control period in 4 communities (July 1995-March 1996) was followed by an intervention period (April 1996-January 1997) when subjects were offered regular, individual diet counselling, physical activity sessions and other activities related to nutrition. RESULTS: The intervention and control groups did not differ at baseline regarding their mean age (24.3 years [SD 6.29] v. 23.8 years [SD 5.86]), mean prepregnancy weight (81.0 kg [SD 19.46] v. 78.9 kg [SD 17.54]) and mean gestational age at recruitment (17.1 weeks [SD 7.06] v. 18.5 weeks [SD 6.92]). The intervention did not result in differences in diet measured at 24-30 weeks' gestation, rate of weight gain over the second half of pregnancy (0.53 kg per week [SD 0.32] v. 0.53 kg per week [SD 0.27]) or plasma glucose level (50 g oral glucose screen) between 24 and 30 weeks (7.21 mmol/L [SD 2.09] v. 7.43 mmol/L [SD 2.10]). Mean birth weights were similar (3741 g [SD 523] v. 3686 g [SD 686]), as was maternal weight at 6 weeks post partum (88.1 kg [SD 16.8] v. 86.4 kg [SD 19.0]). The only changes in dietary intake were a reduction in caffeine (pregnancy) and an increase in folate (post partum). INTERPRETATION: This intervention had only a minor impact on diet; finding ways of encouraging appropriate body weight and activity levels remains a challenge.

Adult↗

The treatment of 'acquired tonsillar herniation' in pseudotumour cerebri.

Acquired tonsillar herniation and syrinx formation are recognized complications of a lumboperitoneal shunt used to treat conditions of increased CSF volume. Treatment of this complication is by ventriculoperitoneal shunt or foramen magnum decompression. We describe the first case of acquired tonsillar herniation in a pseudotumour cerebri (following lumboperitoneal shunt insertion) that responded partly to ventriculoperitoneal shunt insertion and more completely to foramen magnum decompression. Our case demonstrates that a ventriculoperitoneal shunt is not always sufficient in treating this complication and reversing visual deterioration. Foramen magnum decompression may therefore be a sight saving procedure in pseudotumour cerebri with acquired tonsillar herniation and may be important in understanding the pathogenesis of conditions of increased CSF volume.

Adult↗

A novel immunological approach establishes that the auxin-binding protein, Nt-abp1, is an element involved in auxin signaling at the plasma membrane.

Interactions of a collection of monoclonal antibodies (mAbs) to the recombinant Nicotiana tabacum auxin-binding protein 1 (Nt-abp1) were extensively characterized using surface plasmon resonance. Dynamic interaction studies using combinations of Nt-abp1, synthetic peptides corresponding to conserved sequences within auxin-binding proteins, and the mAbs have shown that a number of the mAbs recognized discontinuous epitopes revealing the junction of distinct domains in the folded protein. In particular, the two putative auxin binding domains and the C terminus of the protein were shown to interact with each other in the folded protein. Using the auxin-induced electrical response of tobacco protoplasts as a functional assay, all the mAbs exhibited either auxin antagonist or hormonomimetic properties. These effects, measured for the first time in homologous conditions, confirm that Nt-abp1 is present at the plasma membrane and is involved in the activation of the auxin-dependent electrical response of tobacco protoplasts. Based on our surface plasmon resonance data, we propose that the key event leading to the activation of this auxin electrical response consists of a conformational change in Nt-abp1.

Amino Acid Sequence↗

Human natural immunoglobulin M antibodies induce apoptosis of human neuroblastoma cells by binding to a Mr 260,000 antigen.

Sera of healthy humans contain natural cytotoxic IgM antibodies that specifically recognize a Mr 260,000 antigen (NB-p260) on the surface of human neuroblastoma (NB) cells. Here we demonstrate that anti-NB IgM antibodies prepared from different healthy individuals induce, in all human NB cell lines analyzed thus far, typical morphological and biochemical features of apoptosis including nuclear fragmentation, chromatin condensation, and DNA fragmentation. Both the binding of human anti-NB IgM to NB cells and the induction of apoptosis could be inhibited by preincubation of NB cells with murine IgG raised against purified NB-p260. Furthermore, preincubation of human anti-NB IgM with purified NB-p260 immobilized onto a solid support abolished its ability to induce apoptosis in NB cells. Natural human anti-NB IgM failed to bind to and induce apoptosis in control tumor cell lines that lack expression of NB-p260. The anti-NB IgM-induced apoptotic response was also observed in vivo in xenografted human NB tumors. After a single i.v. injection of anti-NB IgM into nude rats bearing solid NB xenografts, many areas of pyknotic cells with fragmented nuclei were observed that stained positive using the terminal dUTP nick end labeling method. In conclusion, the data demonstrate that natural anti-NB IgM antibodies in the sera of healthy individuals are potent mediators of apoptotic cell death of NB cells both in vitro and in vivo. The NB-p260 antigen was identified as the apoptosis-inducing receptor for anti-NB IgM. Whereas natural anti-NB IgM and NB-p260 may be useful tools for immunotherapy of NB, their biological significance remains to be determined.

Animals↗

Annual health outcomes and treatment costs for schizophrenia populations.

This article describes a model that estimates annual patient health and cost outcomes for schizophrenia under alternative treatment scenarios. We estimate these outcomes for typical antipsychotics and show how treatment with atypical antipsychotics could have an impact on these outcomes. Patients are divided into 5 subcategories--newly diagnosed, no episode, acute episode(s), extended care, and institutionalized--and patient health and cost outcomes are estimated for each category. The proportion of people in each category is estimated for U.S. general, state mental hospital, and community mental health populations. Outcomes include extrapyramidal and moderate/severe schizophrenia symptom days, employed days, suicides, hospital days, and health costs. For patients treated with typical antipsychotics, annual per-patient symptom days ranged from 55 to 365 and costs ranged from $16,000 to $57,000, depending on disease severity. Atypical antipsychotics may reduce symptoms and costs through better efficacy for negative symptoms and better compliance.

Adult↗

A controlled trial of lambda-cyhalothrin-impregnated bed nets and/or dapsone/pyrimethamine for malaria control in Sierra Leone.

A randomized controlled trial investigated the impact of community-wide use of mosquito nets impregnated with lambda-cyhalothrin alone or with dapsone/pyrimethamine (d/p) prophylaxis on clinical malaria due to perennially transmitted Plasmodium falciparum in children in the Bo district of Sierra Leone. The 17 study communities were pair-matched and randomly allocated to receive treated mosquito nets or no nets and the children (age range = 3 months-6 years) in each community were randomly allocated to receive d/p or placebo individually every two weeks. This resulted in each of the approximately 2,000 children recruited being in one of four study groups (impregnated mosquito nets and d/p prophylaxis, impregnated mosquito nets, d/p prophylaxis, and controls). The intervention phase of the study lasted 12 months. A total of 1,800 children attended more than 25% of the 48 total weekly morbidity surveillance surveys and were included in the analysis. The effects of the exclusive use of either treated mosquito nets or d/p prophylaxis on protection against clinical malaria due to P. falciparum was significantly similar (49% and 42%, respectively), while in combination this protective efficacy was significantly increased to 72% (95% confidence interval = 67-76%). Children in the control group had an average of 1.3 clinical malaria episodes per child annually compared with 0.65 episodes or 0.78 episodes for those using treated mosquito nets and d/p, respectively. Children using both treated mosquito nets and d/p prophylaxis had an average of 0.37 episodes per child. The interventions significantly reduced spleen rates and increased hematocrit values, and reduced the duration of episodes of clinical malaria.

Anti-Infective Agents↗

[Establishing a new human neuroblastoma animal model for development of adjuvant therapy methods and for study of metastasis].

We developed a human neuroblastoma animal model in nude rats, which shows high analogy to clinical stage IV disease. 10(7) LAN-1 human neuroblastoma cells were injected in the aorta of nude rats (rnu/rnu). After 5 weeks 6/6 rats developed invasive tumors in the adrenal gland (0.5-3 cm). Micrometastases (1-2 mm) were found in the liver (3 of 6 rats) and the femur (4 of 6 rats). This observation corresponds to the typical clinical finding of advanced neuroblastoma in the adrenal gland and small diffuse liver/bone metastases. A proliferation index of 80% was found in adrenal gland tumors and micrometastases. However, the number of apoptotic cells was different (5% and 50%, respectively). This animal model in nude rats can be used to evaluate the potential of new immunotherapeutic concepts with cytotoxic antibodies and to study the development of metastases.

Animals↗

Expression of a 260 kDa neuroblastoma surface antigen, the target of cytotoxic natural human IgM: correlation to MYCN amplification and effects of retinoic acid.

Human neuroblastoma cells contain a 260 kDa surface-associated antigen (NB-p260) that is recognised by natural cytotoxic IgM antibodies. In this study we demonstrate that NB-p260 is expressed in vivo in a neuroblastoma tumour specimen but not in normal human tissues of neuronal origin. Since MYCN amplification is a clinical marker of neuroblastoma disease progression, we analysed the expression of NB-p260 in human neuroblastoma cell lines with different MYCN amplification status. However, both amplified and non-amplified neuroblastoma cell lines exhibited comparable NB-p260 expression. Treatment of neuroblastoma cells with the differentiation-inducing agent retinoic acid (RA) also had no effect on the expression of NB-p260. Collectively, the data suggest that expression of NB-p260 on human neuroblastoma cells is independent of malignancy and differentiation status of neuroblastoma.

Antigens, Neoplasm↗