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Biomedical subjects

G Faulkner

Publications and source records attributed to G Faulkner.

At least 55 records · Page 3Linked to original sources
PubMed1988

Progression of a human B cell chronic lymphocytic leukemia line in nude mice.

Subcutaneous (s.c.) inoculation of the 85-4LN subline, derived from a lymph nodal metastasis of the Epstein-Barr virus (EBV) transformed human chronic lymphocytic leukemia (CLL) B cell line, EBV-CLL (1), produced progressively growing lethal tumors in 31/35 nonirradiated (88.6%) and 22/25 (88%) of whole-body irradiated (440 rad) nude mice. In contrast, EBV-CLL(1) could produce progressive tumors only in irradiated nude mice. All 85-4LN cells had Epstein-Barr virus nuclear antigen and reacted with pan B and anti-la antibodies. The morphology and ultrastructural features was consistent with the lymphoblastoid nature of the cells. In all s.c. tumor bearing mice, there was enlargement of the spleen and draining lymph nodes. Karyological studies revealed human cells in the spleen and draining nodes in all the mice investigated. Metastases in nonlymphoid organs were seen in 1/8 irradiated and 8/12 nonirradiated mice. The subline contained 77% cells with 47,XY, +12 and 23% cells with 45,XY karyotype. The clone with trisomy 12 did not have any growth advantage either in s.c. transplants or in splenic/lymph nodal metastases. Treatment with the maximum permissible doses of methotrexate (MTX) or chlorambucil (CBL) revealed xenografts to be more sensitive to MTX than CBL. A clone with a 1g+ marker, i.e., 46,XY,Dup(1) (q11----q32) appeared to be associated with resistance to CBL. We have not seen any previous report on the growth and dissemination of human CLL B cells in nonirradiated nude mice. The 85-4LN subline, thus, provides a model for studying the progression, dissemination and therapeutic response of human CLL-B cells.

Animals↗
PubMed1988

Antibody directed targeting of methotrexate-containing small unilamellar vesicles.

The potential of antibody-linked SUVs containing MTX in anticancer therapy was investigated. The SUVs, mean diameter 50 +/- 20 nm, were prepared by probe sonication of MTX-containing MLVs and were covalently linked either to a RAMG or NRG. After incubation with M21 melanoma cells for 2 h, RAMG-linked SUVs showed 2 and 4 times more binding than NRG-linked MTX-containing SUVs or MTX-containing SUVs unlinked to any Ig. Furthermore, on incubating M21 melanoma cells with RAMG-linked 3H MTX-containing SUVs for 2, 4, and 8 h at 4 degrees C or 37 degrees C, a higher radioactivity was associated with cells at 37 degrees C than at 4 degrees C. Membrane immunofluorescence revealed aggregation of and cap formation by RAMG-linked SUVs after 2 h (37 degrees C) and endocytosis at 4 and 8 h at 37 degrees C. Electron microscopic and autoradiographic studies confirmed aggregation of 3H MTX-containing SUVs around and on the surface of M21 cells. Electron microscopy also revealed these SUVs inside invaginations of and under the plasma membrane of melanoma cells. A colony inhibition assay showed that RAMG-linked, MTX-containing SUVs were 60 times, 8 times, and 4.5 times more growth inhibitory than free MTX, NRG-linked MTX-containing SUV, and MTX-containing SUVs unlinked to any Ig, but not toxic to a human kidney cancer line (that did not react with RAMG).

Antibodies, Neoplasm↗
PubMed1987

Prevention of myocardial electrical activity during ischemic arrest with verapamil cardioplegia.

The effect of potassium cardioplegia and potassium cardioplegia containing verapamil hydrochloride on myocardial preservation and electrical activity during prolonged aortic occlusion was examined in 40 adult mongrel dogs. Twenty-four animals (Group 1) received potassium cardioplegia, and 16 animals (Group 2) received potassium verapamil cardioplegia. Potassium or potassium verapamil cardioplegia, 10 ml per kilogram of body weight, was administered after application of the aortic cross-clamp and at 30-minute intervals during the 90-minute arrest. Myocardial temperature was maintained within a range of 8 degrees to 10 degrees C with topical ice saline solution, and electrical activity was monitored with specially designed plunge electrodes. Plunge electrode activity was recorded from the myocardium during arrest in 16 of the 24 animals in Group 1; no electrical activity was present in the animals in Group 2 (p less than .001). The addition of verapamil to potassium cardioplegia increased the tolerance of the myocardium to prolonged ischemia and resulted in less depletion of high-energy phosphate stores and better preservation of mitochondrial ultrastructure and left ventricular function. These data suggest that verapamil augments the preservation provided by potassium cardioplegia by initiating and maintaining a more complete electrical arrest.

Animals↗
PubMed1986

Non-steroidal anti-inflammatory drugs and bleeding peptic ulcer.

Out of all 406 people admitted to hospital with bleeding peptic ulcers over a 2-year period 230 over the age of 60 and their matched community and hospital inpatient controls were interviewed according to a questionnaire designed to obtain details of all drug intake. Non-aspirin non-steroidal anti-inflammatory drugs were taken over twice as often by the patients with bleeding as by the community controls (relative risk 2.7, 95% confidence limits 1.7-4.4) or the hospital controls (relative risk 3.8, 95% confidence limits 2.2-6.4). Confounding seemed unlikely to explain the differences, which were highly significant, were evident for both gastric and duodenal ulcer, and are likely to be important in view of the widespread use of these drugs in elderly people.

Adolescent↗
PubMed1986

Opsonization of Listeria monocytogenes type 4b by human adult and newborn sera.

We studied the requirements for opsonization of Listeria monocytogenes type 4b with chemiluminescence and bactericidal assays and electron microscopy. Preopsonization with 3% adult serum had good opsonic activity (27,300 +/- 11,000 [standard deviation] counts, chemiluminescence assay), while 3% newborn cord serum was not opsonically active (820 +/- 530 counts, P less than 0.001 versus adult serum). In addition, organisms opsonized with cord serum were not killed (0% bacterial killing) and were less frequently visualized intracellularly on electron micrographs (0 to 4 bacteria per cell) than organisms opsonized with adult serum (70% killing and 10 to 20 bacteria per cell). Opsonic requirements for L. monocytogenes type 4b at low concentrations of serum were studied in detail with Sepharose-protein A-treated adult serum to obtain immunoglobulin G (IgG) and IgM fractions and zymosan-absorbed and C4 inactivator-treated serum to obtain alternative and classical complement pathway-deficient sera, respectively. In the presence of complement, IgM was opsonically active (59% of control) while IgG was not (6% of control). In addition, classical complement activity was required for efficient opsonization (greater than 100% of control) while the alternative complement pathway was unnecessary (3% of control). Since IgM is absent and classical complement activity is low in neonatal serum and at the common sites of neonatal Listeria infection, the requirement for IgM and classical complement activity for efficient opsonization of L. monocytogenes type 4b at low serum concentrations may be a factor in the pathogenesis of neonatal disease.

Blood Bactericidal Activity↗
PubMed1986

Effect of small-amplitude electrical activity on myocardial preservation in the cold potassium-arrested heart.

Recent reports indicate that small-amplitude electrical activity may be present in the cold potassium-arrested heart. Twenty-four mongrel dogs were placed on cardiopulmonary bypass and cooled to a rectal temperature of 26 degrees C. Myocardial preservation was provided with a combination of systemic hypothermia 26 degrees C. potassium (20 mEq/L) crystalloid cardioplegic solution (10 ml/kg) infused initially and every 30 minutes during 90 minutes of ischemic arrest, and topical hypothermia. Myocardial temperature was maintained between 8 degrees and 10 degrees C. Electrical activity and transmural myocardial temperature were monitored with specially designed plunge electrodes. Left ventricular stroke work index, cardiac index, and maximum rate of rise of left ventricular pressure were measured before bypass and 45 minutes after ischemic arrest. Biopsy specimens were taken before bypass and at 15 and 45 minutes after ischemic arrest. The specimens were used to measure adenosine triphosphate and to analyze electron microscopic ultrastructure. Small-amplitude electrical activity was present in 16 of 24 animals during cardioplegic arrest. Cardiac index decreased 18 ml/min/kg (not significant), left ventricular stroke work index fell by 0.28 +/- 0.1 gm-m/beat/kg (p less than 0.007), and maximum rate of rise of left ventricular pressure decreased 409 mm Hg/sec (p less than 0.01) in the eight animals without small-amplitude electrical activity. Adenosine triphosphate concentration was unchanged and electron microscopic ultrastructure was well preserved. In contrast, small-amplitude electrical activity (16 animals) resulted in a decrease in cardiac index of 67 ml/min/kg (p less than 0.001), a decrease in left ventricular stroke work index of 0.79 +/- 0.8 gm-m/beat/kg (p less than 0.001), and a fall in maximum rate of rise of left ventricular pressure of 775 mm Hg/sec (p less than 0.001). Adenosine triphosphate concentration decreased from 25 to 21 mumol/gm (p less than 0.04) and electron microscopic ultrastructure was poorly preserved (p less than 0.001). This study demonstrates that small-amplitude electrical activity in the cardioplegia-arrested heart at 10 degrees C impairs myocardial preservation.

Adenosine Triphosphate↗
PubMed1986

Quantification of surfactant pool sizes in rabbit lung during perinatal development.

Methods are presented for the quantitative isolation of surfactants from fetal and newborn rabbit alveolar lavage returns and post-lavaged lung tissue homogenates. The phospholipid content of both fractions progressively increased between 27 days gestation and term (31 days). The tissue-stored fraction increased approximately 16-fold (from 0.48 +/- 0.13 to 7.83 +/- 0.86 mg/g dry lung) and the alveolar fraction more than 30-fold (from 0.08 +/- 0.02 to 2.69 +/- 0.52 mg/g dry lung). Developmental changes in phospholipid composition were also observed. Tissue-stored surfactant was prepared using differential and density gradient centrifugation. Alveolar surfactant was isolated during fetal development as a high-speed pellet following a one-step differential centrifugation. There was little change in the phospholipid content of fetal alveolar lavage supernatant (range 0.12 +/- 0.04 to 0.28 +/- 0.09 mg/g dry lung). By the first postnatal day the phospholipid content of both lavage fractions significantly increased (pellet, 7.51 +/- 1.79; supernatant, 4.01 +/- 1.36 mg/g dry lung) and both were identified as surfactant. This increase in alveolar surfactant was accompanied by an approximately twofold decrease (to 3.81 +/- 1.1 mg/g dry lung) in the tissue-stored fraction. These data provide a quantitative profile of surfactant accumulation and secretion in developing rabbit lung.

Animals↗
PubMed1984

Reverse transformation of Chinese hamster ovary cells by methyl xanthines. Structure-function relationships.

Using a number of drugs that increase cellular cAMP levels, alterations in the amount of cell surface fibronectin and other transformation parameters were studied in Chinese hamster ovary (CHO) cells. The drugs include db-cAMP, different methylxanthines (theophylline, aminophylline, methyl isobutyl xanthine (MIX), caffeine and theobromine), papaverine and cholera toxin. Methylxanthines that have a methyl group at the seventh position lack reverse transforming potential; those that lack a methyl group at the seventh position induced reverse transformation in CHO cells, causing an increase in surface fibronectin, cell substratum adhesive strength and anchorage dependence for growth. Further, as methyl xanthines are substituted in other positions different from the seventh position, the more efficient they become in restoring normal phenotypic properties; the later agents also induced low saturation density via a cytostatic state causing accumulation of cells in the S and G2 phases of the cycle in contrast to the G1 arrest of normal cells at low saturation density. db-cAMP and cholera toxin induced cell elongation but like caffeine and theobromine, did not induce surface fibronectin. The non-methylxanthine phosphodiesterase inhibitor papaverine induced neither cell elongation nor surface fibronectin but produced a cytostatic effect similar to aminophylline and MIX. These studies suggest that the reverse transformation properties fall into two groups: (a) Differentiation-related properties including cell morphology, parallel alignment and surface matrix fibronectin, etc.; (b) cell cycle-related properties-low saturation density, cell arrest at G1 phase and anchorage-dependent growth. Phosphodiesterase inhibitors reversibly eliminate indefinite division potential of CHO cells by inducing a cytostatic situation and not by inducing a G1-specific arrest.

Animals↗
PubMed1984

An antigen cross-reacting with anti-laminin sera is found in the submembranous cortical region of various cells in culture.

Laminin is a complex extracellular matrix molecule consisting of one A-subunit (Mr400KD) and 3 B-subunits (Mr220KD) and is found in the basement membrane. Even though it is now apparent that different cell types are synthesizing laminin-like molecules, the role of these molecules in different systems is not well understood. We have characterized laminin and raised specific antiserum in rabbits. The distribution of laminin was studied by indirect immunofluorescence in different cells such as PFHR-9, WI-38, MRC-5, CHO, 3T3, WI38VA132RA, RAW264-7 and Ki3T3. All normal and transformed cells display a high amount of intracellular submembranous network-like component cross-reacting with antilaminin serum (anti-Lm) and not with anti-fibronectin (anti-Fn) serum as seen by immunofluorescence in permeabilized cells. Preabsorption of anti-Lm with increasing amounts of laminin progressively decreased the staining of the submembranous network. Anti-Lm sera from four other laboratories also showed similar staining pattern. The structural and non-secretory nature of this submembranous staining was confirmed by (a) inhibiting protein synthesis in 0.5% serum and 4 micrograms/ml puromycin and (b) by immunoelectron microscopy of permeabilized cells. Immunoprecipitation of 3H-leucine labelled cellular proteins with anti-laminin sera showed proteins of Mr 220-210 KD in SDS-PAGE fluorography. These studies suggest that an antigen(s) crossreacting with anti-Lm sera is localized in the membrane associated cytoskeletal region where spectrin/fodrin family of proteins have been localized.

Animals↗
PubMed1981

Phagocytosis of Candida albicans in chronic mucocutaneous candidiasis.

Inasmuch as human monocytes are able to kill Candida albicans (C. albicans) only through oxidative pathways, which also produce chemiluminescence (CL), CL was used to assess the ability of polymorphonuclear neutrophils and monocytes to phagocytose and kill C. albicans in a 12-year-old girl with chronic mucocutaneous candidiasis. In contrast to normal mononuclear cells (monocytes and lymphocytes), mononuclear cells from the patient did not respond with a CL burst when mixed with opsonized C. albicans (peak CL, 55 versus 105 cpm X 10(-3) for control). Phagocytosis of C. albicans by monocytes, assessed by electron microscopy, was normal. The patient's mononuclear cells did produce CL when mixed with Candida parapsilosis (peak CL, 68 versus 72 cpm X 10(-3) for control) or zymosan (peak CL, 149 versus 180 cpm X 10(-3) for control). Myeloperoxidase activity in monocytes assessed by light microscopy was normal. However, peroxidase activity in the patient's monocytes persisted in glass-adherent monocyte-macrophages after 5 days incubation, suggesting that her cells may mature poorly. In contrast to the poor CL response of monocytes to C. albicans, polymorphonuclear neutrophils from the patient had increased CL (peak, 858 versus 458 cpm X 10(-3) for control). Also, the patient's serum showed increased opsonic activity for C. albicans (peak, 1800 versus 1100 cpm X 10(-3) for control).

Candida albicans↗
PubMed1979

Defective interfering particles modulate VSV infection of dissociated neuron cultures.

Infection of dissociated neuron cultures of mice with VSV and its defective particle DI-T was studied using fluorescent light microscopy as well as transmission and scanning electron microscopy. When cultures are infected with wild virus, VSV replicates selectively in neurons, producing cell death within 24-48 hr. Sensory and immature neurons express viral antigen most rapidly. Viral antigen and viral budding sites are detected along the neuron soma and dendrites. When large amounts of DI-T particles are added to the wild virus inoculum, viral growth is completely suppressed in mature neurons, the cell killing effects of VSV are considerably delayed and co-infected cultures survive for 5-16 days. Viral antigen accumulates in cytoplasmic inclusions and on the membrane of neuron cell somas and dendrites in the virtual absence of viral assembly. Identical modulation of VSV infection in mature neuron cultures is obtained when DI-T particles are added before or after the wild virus, but ultraviolet inactivation of DIs completely abolishes their protective effect. Immature neurons or Vero cells cannot be protected from acute cytopathic changes by an equivalent amount of DI particles. Thus DIs interfere with replication and assembly of the wild virus and attenuate cell killing effects in mature neurons in vitro.

Animals↗
PubMed1978

Apparent replication of an unusual virus-like particle in both a parasitoid wasp and its host.

Nuclear inclusion bodies are found in the hemocytes of all tussock moth larvae parasitized by the braconid wasp Apanteles melanoscelus. These inclusion bodies represent the apparent site of replication of an unusual virus-like particle. Identical particles are observed in the nuclei of a small number of parasitoid calyx cells and are probably transmitted to host larvae during oviposition.

Animals↗
PubMedDate not supplied

Development towards multimedia medical workstations.

In this paper, concepts and examples of medical workstations with multimedia and hypermedia capabilities will be presented. These workstations have special hardware and software requirements. Also described in the article are the developments in Europe (AIM project line) within this area.

Computer Communication Networks↗
PubMedDate not supplied

Freeze substitution technique for identifying liposomes incorporated in emulsion and gel preparations.

The freeze-substitution technique was utilized for identifying unilamellar and multilamellar liposomes incorporated in gel or emulsion preparations. Samples of each preparation were rapidly frozen in liquid propane and the ice formed in the process was substituted with acetone containing 2 per cent osmium tetroxide at -70 degrees C. Electron micrographs obtained by both freeze-fracture and freeze-substitution methods showed the presence of either small unilamellar or multilamellar vesicles in all the liposome preparations. Results clearly demonstrated that freeze-substitution is a simple and cost-effective technique in comparison to the traditional freeze-fracture method and can be successfully used to characterize liposomes incorporated in dermatological or cosmetic vehicles.

Emulsions↗
PubMedDate not supplied

Liposomal drug delivery to the eye and lungs: a preliminary electron microscopy study.

Colloidal gold was used as an electron-dense marker for multilamellar vesicles to study the mechanism of liposome drug delivery to the eye and lung. A gold labelled multilamellar vesicle could be seen in the conjunctiva but there was no evidence of vesicles adsorbed to the epithelial surface of cornea or conjunctiva. In the lung, a free gold particle was isolated in type 1 epithelial cells and many vesicular structures were observed in the alveolar spaces which were not gold labelled. Experiments performed so far indicate that adsorption and not endocytosis was the major mechanism of uptake of drug or marker for multilamellar vesicles except for conjunctiva.

Adsorption↗
PubMedDate not supplied

Predicting physical activity promotion in health care settings.

PURPOSE: To test the ability of the theory of planned behavior (TPB) in predicting the stage of change for physical activity promotion by mental health professionals. DESIGN: Six-month prospective questionnaire study. SETTING: One mental health trust in the East Midlands, United Kingdom. SUBJECTS: Three hundred ninety-four mental health professionals (men, n = 131; women, n = 263) of an initial sample of 477 participated in the study (83% response rate). MEASURES: Attitudes, subjective norms, intentions, perceived behavioral control, and stage of change were measured at the first wave of data collection. Stage of change was also assessed 6 months later. Data were analyzed using structural equation modeling. RESULTS: Intention and stage of change were successfully predicted from TPB variables. Overall, 27% of the variance in self-reported stage of promoting physical activity was explained by the model. Sixty-one percent of the variance in intention to promote physical activity was explained. When included, past behavior was the strongest predictor of both intention and stage of change and attenuated all other path coefficients. Past behavior improved the predicted variance in intention by 11% and stage by 6%. CONCLUSIONS: The TPB variables of attitude, subjective norms, perceived behavioral control, and intention predict stage of change of physical activity promotion in a health care setting. However, promoting physical activity in the past had a sizable effect on predicting subsequent promotion. Due to unequal distribution across stages, the stage model's application to understanding the behavior of health professionals may be limited.

Adult↗
PubMedDate not supplied

Mechanical evaluation of craniofacial osseointegration retention systems.

This study evaluates mechanical behavior of retention systems that have been used in craniofacial osseointegration. A loading/measuring apparatus was custom designed and constructed. Test bases that represented a typical auricular situation were constructed. These bases allowed for three points of retention. Jigs that could be reproducibly positioned carried the reciprocal portion of the retentive components. The test apparatus provided vertical and horizontal loads in five locations. The system was used to test two ball-and-socket attachments (Dalla Bona; Nobelpharma), cast and preformed bar and clips (Nobelpharma), and three magnet systems (Dynamag; Neomag; Technovent). The loading/measuring apparatus was also used to evaluate the performance of two facial prosthetic adhesives. Retention systems employed in craniofacial osseointegration offer more predictable retention than the facial prosthetic adhesives. The mechanical retention systems are best suited to situations where tensile and shear forces will operate. Magnet systems are best used where only tensile forces are anticipated or where horizontal forces on the implants are to be avoided.

Adhesives↗