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Biomedical subjects

D Paul

Publications and source records attributed to D Paul.

At least 19 recordsLinked to original sources
PubMed2006

Antioxidant vitamins E and C as adjunct therapy of severe acute lower-respiratory infection in infants and young children: a randomized controlled trial.

OBJECTIVE: To evaluate the effect of antioxidant Vitamins E and C as adjunct therapy of severe acute lower respiratory infection (ALRI) in children. DESIGN: Randomized double-blind placebo-controlled clinical trial. SETTING: A large childrens' hospital serving the urban poor in Kolkata, India. SUBJECTS: Children aged 2-35 months admitted with severe ALRI. INTERVENTION: In total, 174 children were randomly assigned to receive alpha-tocopherol 200 mg and ascorbic acid 100 mg twice daily or placebo for 5 days. All children received standard treatment for severe ALRI. Outcome measures were: time taken to recover from a very ill status, fever, tachypnoea, and feeding difficulty; and improvement in oxidative stress and immune response indicated by thiobarbituric acid reacting substances (TBARS) and response to skin antigens, respectively. RESULTS: Recovery rate ratios (95% CI) using proportional hazards model were 0.89 (0.64-1.25), 1.01 (0.72-1.41), 0.86 (0.57-1.29), and 1.12 (0.77-1.64) for very ill status, feeding difficulty, fever, and tachypnoea, respectively. TBARS values were high and similar in the two groups at admission, discharge, and at 2 weeks follow-up. Serum alpha-tocopherol significantly increased in treated group at discharge. Immune response to skin antigens were very poor at admission and after 2 weeks, in both groups. CONCLUSION: Infants with severe ALRI failed to benefit from two antioxidant nutrients as adjunct therapy. Severe ALRI in infants may cause cell-mediated immune dysfunction. We need a better understanding of oxidative processes in growing infants to help us better design interventions with antioxidant therapy.

Acute Disease↗
PubMed2005

Building blocks for self-assembled porphyrinic photonic wires.

[structure: see text] Based on the high affinity of phenanthroline-strapped porphyrins for imidazoles, building blocks for self-assembled, linear porphyrin architectures have been designed. Their synthesis is reported, and the assembly principle is illustrated by the formation of the shortest possible scaffold. Only one type of assembly is observed, and the stepwise energy transfer from the boron dipyrrylmethane (BODIPY) input to the free base output is highly efficient.

Journal Article↗
PubMed2005

Growth of human cells on polyethersulfone (PES) hollow fiber membranes.

A novel material of porous hollow fibers made of polyethersulfone (PES) was examined for its ability to support the growth of human cells. This material was made in the absence of solvents and had pore diameters smaller than 100 microm. Human cell lines of different tissue and cell types (endothelial, epithelial, fibroblast, glial, keratinocyte, osteoblast) were investigated for adherence, growth, spread and survival on PES by confocal laser microscopy after staining of the cells with Calcein-AM. Endothelial cell attachment and growth required pre-coating PES with either fibronectin or gelatin. The other cell types exhibited little difference in growth, spread or survival on coated or uncoated PES. All the cells readily adhered and spread on the outer, inner and cut surfaces of PES. With time confluent monolayers of cells covered the available surface area of PES and in some cases cells grew as multilayers. Many of the cells were able to survive on the PES for up to 7 weeks and in some cases growth was so extensive that the underlying PES was no longer visible. Scanning electron microscope observations of cells on the materials correlated with the confocal morphometric data. Thus, PES is a substrate for the growth of many different types of human cells and may be a useful scaffolding material for tissue engineering.

Biocompatible Materials↗
PubMed2003

Increased susceptibility to the tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in transgenic mice overexpressing c-myc and epidermal growth factor in alveolar type II cells.

PURPOSE: As previously described, SPC/myc transgenic mice developed bronchioloalveolar adenocarcinomas derived from alveolar type II (AT II) cells within 10-14 months, whereas SPC/IgEGF transgenic mice developed hyperplasias. Our purpose was to determine the potential interplay of environmental and genetic factors in lung tumorigenesis. MATERIALS AND METHODS: Six-week-old SPC/myc and SPC/IgEGF transgenic mice, overexpressing c-myc and a secretable form of the epidermal growth factor (IgEGF) under the control of the surfactant protein C (SPC) promoter, were treated with a single dose of the tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). As control groups, SPC/myc and SPC/IgEGF transgenic mice were treated with NaCl and non-transgenic littermates were treated with NNK or NaCl, respectively. RESULTS: After 6 months, none of the NaCl-treated transgenic littermates showed bronchioloalveolar hyperplasia and adenocarcinoma formation, whereas 100% of the NNK-treated SPC/myc transgenic mice did. The effect of NNK on SPC/IgEGF transgenic mice was less pronounced, inducing hyperplasia in the lung in only 16.7% of them. In 90% of the NNK-treated non-transgenic littermates no neoplastic changes were detected in the lung. CONCLUSIONS: These results demonstrate that the progression of pulmonary bronchioloalveolar adenocarcinomas, induced by expression of c-myc as a transgene, was accelerated by NNK, suggesting that c-myc cooperates with NNK-induced mutations.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed2003

Surface properties of and cell adhesion onto allylamine-plasma-coated polyethylenterephtalat membranes.

Allylamine was plasma polymerised onto a polyester (PET) membrane to obtain a surface with good cell adhesive properties. Samples were coated using a microwave plasma source operating at different process parameters. The effect of process parameters on the physical, and chemical properties of plasma-polymerised-allylamine (PPAa) was evaluated by studying elemental composition, amine concentration, wettability, and surface morphology. A relatively high amine concentration was measured (up to 50 nmol/cm2). In parallel, nitrogen enrichment was observed after exposure to high-energetic plasma. Irrespective of the treatment conditions, oxygen was incorporated into the polymer structure. PPAa surfaces were found to be more hydrophilic than PET. The wettability of the samples increased with increasing amine concentration. Pictures from scanning electron microscopy indicated that homogeneous pinhole-free PPAa layers were deposited on PET membranes, without a significant change of permeability. In vitro evaluation of biocompatibility was carried out by studying human skin fibroblast interaction with surfaces. Cell attachment and viability on PPAa layers were found to be more intensive than on the control PET, based on the higher metabolic activity of adhering cells, but also on morphological criteria including overall cell morphology.

Allylamine↗
PubMed2003

Constitutive and inducible expression of CYP enzymes in immortal hepatocytes derived from SV40 transgenic mice.

1. The expression of liver-specific transcription factors and cytochrome P450 (CYP) enzymes have been studied in three new hepatocyte-like cell lines derived from SV Delta 202 transgenic mice: AMH-Delta 202 (adult mouse hepatocytes), TAMH-Delta 202 (tumour-derived adult mouse hepatocytes) and NMH-Delta 202 (newborn mouse hepatocytes). 2. mRNA levels of liver-enriched transcription factors such as D-element binding protein (DBP), liver-enriched transcription activating protein (LAP) and the hepatic nuclear factors (HNF) 1, 2 and 3 in all Delta 202 transgenic hepatocyte lines were similar to those in the wild-type liver and in primary mouse hepatocytes. 3. Analysis of basal CYP activities and testosterone metabolism revealed that Delta 202 cells showed higher similarities to mouse hepatocytes than Hepa 1c1c7 hepatoma cells. All three Delta 202 cell lines exhibited substantial active CYP1A1/2, CYP2A4/5 and CYP3A11 activities and lower levels of CYP2B, CYP2C and CYP2E1 activities. 4. The Delta 202 cells also responded to model inducers. 3-Methylcholanthrene induced CYP1A1/2 (7-ethoxyresorufin O-deethylation); phenobarbital induced CYP2B (7-benzoxyresorufin O-debenzylation), CYP2A4/5 (testosterone 7alpha -hydroxylation) and CYP3A11 (testosterone 6beta -hydroxylation); and rifampicin and dexamethasone induced CYP3A11 activities in the three Delta 202 cell lines, whereas only AMH-Delta 202 cells reproduced to a limited extent the response of CYP2E1 to ethanol observed in hepatocytes. 5. The results suggest that generation of hepatocyte lines from transgenic animals constitutes a successful approach to obtain in vitro models alternative to primary hepatocytes for drug metabolism and CYP inducibility studies.

Animals↗
PubMed2003

Expression of active human blood clotting factor VIII in mammary gland of transgenic rabbits.

Human clotting factor VIII is probably the largest protein to be expressed to date in the mammary gland of a transgenic animal, and it requires extensive posttranslational modification to achieve full biological activity. The mammary gland specific construct mWAP-hFVIII-MT-I was injected into the pronuclei of rabbit zygotes, and three transgenic offspring were obtained. Founder 385 showed germ-line transmission of a single integrated copy, and a homozygous line was established from this animal. The rhFVIII was transcribed and translated exclusively in the mammary gland. The activity of rhFVIII in the rabbit milk ranged from 5 to 8% of that found in normal human plasma. Results indicate the suitability of the transgenic rabbit mammary gland for rhFVIII production.

Animals↗
PubMed2002

Risk factors for pneumonia in infants and young children and the role of solid fuel for cooking: a case-control study.

We evaluated the risk factors for childhood pneumonia with particular reference to indoor air-pollution associated with solid fuel use for cooking (e.g. coal, wood, dung), using a case-control study in a children's hospital in Calcutta. Cases were 127 children aged 2-35 months of either sex admitted with pneumonia and controls were 135 children attending their immunization clinic. Solid fuel use (odds ratio = 3.97, CI = 2.00-7.88), history of asthma in the child (OR = 5.49, CI = 2.37-12.74), poor economic status indicator (OR = 4.95, CI = 2.38 to 10.28), keeping large animals (OR = 6.03, CI = 1.13-32.27) were associated with high risk of pneumonia after adjusting for confounding (logistic regression analysis). Nearly 80% of people in India use such smoke producing fuel and the population attributable risk would be very high. This finding has important health policy implications. Furthermore, history of asthma is a useful prognostic indicator for early action for prevention of severe pneumonia.

Air Pollution, Indoor↗
PubMed2002

Polyetherimide: a new membrane-forming polymer for biomedical applications.

Membranes for biohybrid organs such as the biohybrid liver support system have to face 2 different environments, namely blood and tissue cells. Accordingly, the respective membrane surfaces must have optimal properties in terms of biocompatibility for blood or tissue. Flat membranes prepared by a phase inversion process from polyetherimide were modified by binding of tris-(hydroxymethyl)-aminomethane to obtain a surface with hydroxyl groups by binding of polyethylene imine to attach a hydrophilic macromolecule with amine groups useful as a spacer for later bonding of further ligands and by attachment of heparin. The binding of the different ligands was successful as monitored by different physicochemical methods. The blood response of plain polyetherimide was comparable to that of polyacrylonitrile, and it could be further improved by the binding of heparin. The tissue compatibility of polyetherimide and its different modifications was compared with commercial cell culture substrate membranes (Millicell) and found to be comparable for polyetherimide and even better after the modification with tris-(hydroxymethyl)-aminomethane. In conclusion, polyetherimide seems to be an interesting material for the production of membranes for application in biohybrid organ systems.

Complement Activation↗
PubMed2002

Application of cDNA arrays to monitor mRNA profiles in single preimplantation mouse embryos.

Array technology is a widely used tool for gene expression profiling in various biological systems. However, the application of this method to mammalian preimplantation embryos is limited by the small amount of mRNA that can be extracted from a single embryo, which is not sufficient for array analysis. Here we report a protocolfor the rapid global amplification of embryonic mRNA that permits the generation of expression profiles from single murine blastocysts. The approach combines global PCR and 77 RNA polymerase amplification and allows the preparation of labeled, amplified RNA for array hybridization from single murine blastocysts containing approximately 1.5 pg mRNA in less than 12 h. We demonstrate that this amplification procedure is highly reproducible and does not bias original relative mRNA levels. Signal patterns from various embryonic stages of murine development revealed marked differences in mRNA expression that were in accordance with previously published data. We found genes known to be involved in embryonic apoptosis expressed at different levels in individual murine day 3.5 blastocysts. This technique can thus be used to assess embryonic viability and investigate molecular mechanisms of embryonic development.

Animals↗
PubMed2001

Cytomegalovirus early promoter induced expression of hCD59 in porcine organs provides protection against hyperacute rejection.

The critical shortage of human donor organs has generated growing interest for porcine to human xenotransplantation. The major immunological barrier to xenotransplantation is the hyperacute rejection (HAR) response that is mediated by preformed xenoreactive antibodies and complement. A promising strategy to control the complement activation, is the expression of human complement regulatory proteins in transgenic animals. We have used the human early cytomegalovirus (CMV) promoter to drive expression of the human complement regulatory protein CD59 (hCD59) in transgenic pigs. A total of eight live transgenic founder animals was born from which five transgenic lines could be established. mRNA analysis and Western blotting revealed high expression of hCD59 in heart, kidney, skeletal muscle, and skin in animals of lines 1 and 5, as well as in the pancreas of four lines. This pattern of expression was confirmed by immunhistological staining. A cell-specific expression in heart and kidney tissue of transgenic lines 1 and 5 was determined. Primary fibroblasts and endothelial cell cultures derived from the aorta of transgenic pigs showed a significantly diminished sensitivity against the challenge with xenoreactive human antibodies and complement whereas non-transgenic control cells were highly susceptible to complement mediated lysis. Ex vivo perfusion of kidneys with pooled human blood revealed a significant protective effect of hCD59 against HAR. The average survival of transgenic kidneys was significantly extended (P<0.05) over nontransgenic controls (207.5+/-54.6 vs. 57.5+/-64.5 min). These data support the concept that hCD59 protects nonprimate cells against human complement mediated lysis and suggest that donor pigs transgenic for hCD59 could play a crucial role in clinical xenotransplantation. Two of five hCD59 transgenic lines showed strong hCD59 expression in several organs relevant for xenotransplantation and a protective effect against HAR. This indicates that the use of the CMV-promoter can facilitate the selection process for optimized transgene expression.

3T3 Cells↗
PubMed2001

Delivering adjuvant chemotherapy to women with early-stage breast carcinoma: current patterns of care.

BACKGROUND: Variations in practice patterns are markers for the quality of patient care in general medicine, but little is known about variation in care delivered to cancer patients. This study's purpose was to describe chemotherapy use, variations in chemotherapy delivery, and the incidence of complications in community practice settings. METHODS: Data describing adjuvant chemotherapy for patients with early-stage breast carcinoma (ESBC) were collected from an ongoing Oncology Practice Pattern Study at 13 large managed care, academic, and community practices (1111 patients). Data collection included information about diagnoses and adjuvant chemotherapy treatments, laboratory results, supportive care, complications, and treatment modifications. RESULTS: The median patient age was 50 years, and most patients had zero to three positive lymph nodes. Chemotherapy regimens consisting of cyclophosphamide, methotrexate, and 5-fluororacil (CMF) and of doxorubicin and cyclophosphamide (AC) accounted for 76% of the adjuvant therapies used. Overall, 30% of patients had delivered average relative dose intensities </= 85% of the referenced targets. Delivered summation dose intensities (SDIs) frequently were well below targeted SDIs. Neutropenia-related dose modifications occurred for 27.6% of patients and recurred with a 60.7% rate. AC was the regimen delivered with a dose intensity closest to the referenced target. However, patients who were treated with AC regimens and with regimens consisting of cyclophosphamide, doxorubicin, and 5-fluorouracil had significantly higher rates of chemotherapy-related complications compared with patients who were treated with CMF regimens in the most recent treatment years. CONCLUSIONS: Adjuvant chemotherapy for patients with ESBC frequently is not administered as referenced in off-protocol community settings. Variation in the delivered SDI raises concerns about potential treatment outcomes and warrants strategies to identify patients who are at risk for complications early in therapy.

Adult↗
PubMed2001

Development of pulmonary bronchiolo-alveolar adenocarcinomas in transgenic mice overexpressing murine c-myc and epidermal growth factor in alveolar type II pneumocytes.

Transgenic mouse models were established to study tumorigenesis of bronchiolo-alveolar adenocarcinomas derived from alveolar type II pneumocytes (AT-II cells). Transgenic lines expressing the murine oncogene c- myc under the control of the lung-specific surfactant protein C promoter developed multifocal bronchiolo-alveolar hyperplasias, adenomas and carcinomas respectively, whereas transgenic lines expressing a secretable form of the epidermal growth factor (IgEGF), a structural and functional homologue of transforming growth factor alpha (TGF alpha), developed hyperplasias of the alveolar epithelium. Since the oncogenes c- myc and TGF alpha are frequently overexpressed in human lung bronchiolo-alveolar adenocarcinomas, these mouse lines are useful as models for human lung bronchiolo-alveolar adenocarcinomas. The average life expectancies of hemizygous and homozygous c- myc transgenics were 14.25 months and 9.2 months, respectively, suggesting that a dosage effect of c- myc caused an accelerated bronchiolo-alveolar adenocarcinoma formation. First analyses of double transgenics, hemizygous for both c- myc and IgEGF, show that these mice develop bronchiolo-alveolar adenocarcinomas at the average age of 9 months, indicating that these oncogenes cooperate during the lung cancer formation. Our results demonstrate that c- myc and EGF are directly involved and cooperate with one another during formation of bronchiolo-alveolar adenocarcinomas in the lung.

Adenocarcinoma↗
PubMed2001

[Retinal degeneration. Apoptosis as pathomechanism and therapy strategy].

Molecular techniques in ophthalmology and related subjects have led in recent years to the identification of many genes expressed in photoreceptor cells and have allowed the characterization of mutations leading to distinct phenotypes of retinal degeneration. Programmed cell death, or apoptosis, has been identified as the final common pathway in this disease group. A cascade of events has evolved, starting with specific stimuli and developing over different mediators and regulators (e.g., Fas ligand, proteins of the Bcl-2 family, p53) to effector enzymes (caspases). The ever increasing data of this pathway serve as a basis for new therapeutic strategies. We review the current knowledge on apoptosis in retinal degeneration.

Animals↗
PubMed2001

A new module arrangement for plasmapheresis.

On-line plasmapheresis using microporous membranes for filtration normally requires two external circulations (double treatment) before the detoxified plasma can be returned to the patient. The duomodule, a new filter arrangement developed by our group, integrates both steps in one equipment module using only one external circuit. Separations of aqueous polyethylene glycol (PEG) solutions as well as human plasma were carried out using the duomodule arrangement. The results revealed a considerable decrease of higher molecular substances in the feed solutions and a significant increase of these components in the permeate solution accumulated in the external compartment of the module. In conclusion, the duomodule arrangement seems to be an useful tool for the therapeutic apheresis.

Chemical Fractionation↗
PubMed2001

Uteroglobin promoter-targeted c-MYC expression in transgenic mice cause hyperplasia of Clara cells and malignant transformation of T-lymphoblasts and tubular epithelial cells.

To investigate the influence of the proto-oncogene c-MYC on tumor development in different epithelial tissues which secrete Clara Cell Secretory Protein (uteroglobin, UG), transgenic mouse lines were established expressing the human c-MYC proto-oncogene under the control of the rabbit UG-promoter. These mice expressed the c-MYC transgene in Clara cells and other UG expressing tissues like uterus and prostate. In the bronchioalveolar epithelium of the lung hyperplasias developed originating from Clara cells. Surprisingly, transgenics most frequently developed T-lymphoblastic lymphomas, a polycystic kidney phenotype and renal cell carcinoma derived from tubular epithelial cells, which are both tissues that had so far not been known to express UG. Immunohistological studies in UG/MYC transgenics and in a transgenic line (UG/eGFP) expressing Green Fluorescent Protein confirmed that the uteroglobin promoter is not only active in Clara cells, but also in tubular epithelial cells of the kidney and in lymphatic tissue. The UG/MYC transgenics will be useful to investigate the biochemical mechanisms underlying the development of carcinomas and the oncogenic properties of c-MYC in epithelial cells of various tissues.

Animals↗
PubMed2001

Progressive atrioventricular conduction defects and heart failure in mice expressing a mutant Csx/Nkx2.5 homeoprotein.

A DNA nonbinding mutant of the NK2 class homeoprotein Nkx2.5 dominantly inhibits cardiogenesis in Xenopus embryos, causing a small heart to develop or blocking heart formation entirely. Recently, ten heterozygous CSX/NKX2.5 homeoprotein mutations were identified in patients with congenital atrioventricular (AV) conduction defects. All four missense mutations identified in the human homeodomain led to markedly reduced DNA binding. To examine the effect of a DNA binding-impaired mutant of mouse Csx/Nkx2.5 in the embryonic heart, we generated transgenic mice expressing one such allele, I183P, under the beta-myosin heavy chain promoter. Unexpectedly, transgenic mice were born apparently normal, but the accumulation of Csx/Nkx2.5(I183P) mutant protein in the embryo, neonate, and adult myocardium resulted in progressive and profound cardiac conduction defects and heart failure. P-R prolongation observed at 2 weeks of age rapidly progressed into complete AV block as early as 4 weeks of age. Expression of connexins 40 and 43 was dramatically decreased in the transgenic heart, which may contribute to the conduction defects in the transgenic mice. This transgenic mouse model may be useful in the study of the pathogenesis of cardiac dysfunction associated with CSX/NKX2.5 mutations in humans.

Age Factors↗