Biomedical subjects

J E Morris

Publications and source records attributed to J E Morris.

At least 37 records · Page 2Linked to original sources

PubMed1999

Preclinical evaluation of a rheolytic catheter for percutaneous coronary artery/saphenous vein graft thrombectomy.

The presence of thrombus increases the rate of acute complications and restenosis in percutaneous revascularization of native coronary arteries and saphenous vein grafts. Rheolytic thrombectomy uses high velocity saline jets to create a Bernoulli effect for thrombus entrainment, dissociation, and evacuation of debris, providing a novel approach to the treatment of thrombotic lesions. The study objective was to determine the preclinical safety and effectiveness of a 5 French rheolytic thrombectomy catheter designed for use in coronary arteries and saphenous vein grafts. In vitro testing was performed to evaluate catheter effectiveness (clot removal rate) and safety (particle generation and hemolysis). This was followed by acute (n = 6) and chronic (n = 6) canine studies to determine hemodynamic, angiographic, and histopathologic effects of the catheter. The results showed effective clot removal with minimal embolization: 99.4% of the total clot volume was removed with only 0.1% proximal embolization and 0.5% distal embolization. 98.4% of the embolic particles were less than 10 microm. Canine studies revealed no significant angiographic, hemodynamic, histopathologic, or electrocardiographic abnormalities with the exception of transient heart block in one animal. There was transient hemolysis which normalized within 24 hours with no adverse effects. These results demonstrate the effectiveness and safety of coronary rheolytic thrombectomy and provided the basis for clinical trials to further evaluate this promising new approach for coronary thrombectomy.

Animals↗

PubMed1998

Sonoporation of erythrocytes by lithotripter shockwaves in vitro.

Sonoporation of red blood cells was examined in relation to cavitation-induced hemolysis. FITC-dextran at 580,000 MW was added to suspensions of canine erythrocytes and the mixture was exposed to lithotripter shockwaves. Exposure at 5% or 50% hematocrit in PBS or 50% in plasma yielded not only hemolysis but also FITC-dextran uptake in surviving cells. Hemolysis increased with increasing numbers of shockwaves. The numbers of cells with fluorescent dextran uptake remained roughly constant for 250-1000 shockwaves, but this represented an increasing percentage of the surviving cells. In addition, fluorescent microspheres formed spontaneously in samples with hemolysis. An air bubble was needed in the chamber to obtain substantial effects, implicating the cavitation mechanism. The exposure-response trends could be modeled by simple theory for random interaction of the cells with bubbles.

Air↗

PubMed1998

Lack of a co-promoting effect of a 60 Hz magnetic field on skin tumorigenesis in SENCAR mice.

It has been proposed that extremely low frequency (ELF) magnetic fields may enhance tumorigenesis through a co-promotional mechanism. This hypothesis has been further tested using the two-stage model of mouse skin carcinogenesis, i.e. 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced promotion of skin tumors in mice initiated by a single subcarcinogenic dose of 7,12-dimethylbenz[a]anthracene. Experimentation described herein utilized the SENCAR mouse and examined the effect of a magnetic field on skin tumor promotion induced by three different doses of TPA within its dose-response range, i.e. 0.85, 1.70 or 3.40 nmol, administered twice per week. SENCAR mice (56/treatment group) were exposed to a 60 Hz magnetic field having a flux density of 2 mT for 6 h/day for 5 days/week and compared with mice exposed to the ambient magnetic field. Tumor incidence and multiplicity were monitored weekly for 23 weeks of TPA promotion. Statistical evaluation of the effects of the magnetic field on tumor incidence and multiplicity did not reveal any statistically significant effects; thus, within the sensitivity limits imposed by the animal model and the exposure parameters employed, no promotional or co-promotional effect of a 2 mT magnetic field on skin tumor development in SENCAR mice could be demonstrated.

Animals↗

PubMed1997

Comparison of DNA-lipid complexes and DNA alone for gene transfer to cystic fibrosis airway epithelia in vivo.

Cationic lipids show promise as vectors for transfer of CFTR cDNA to airway epithelia of patients with cystic fibrosis (CF). However, previous studies have not compared the effect of DNA-lipid to DNA alone. Recently, we developed a formulation of plasmid encoding CFTR (pCF1-CFTR) and cationic lipid (GL-67:DOPE) that generated greater gene transfer in mouse lung than previously described DNA-lipid vectors. Therefore, we tested the hypothesis that DNA-lipid complexes were more effective than DNA alone at transferring CFTR cDNA to airway epithelia in vivo. We administered complexes of DNA-lipid to one nostril and DNA alone to the other nostril in a randomized, double-blind study. Electrophysiologic measurements showed that DNA-lipid complexes partially corrected the Cl- transport defect. Importantly, the pCF1-CFTR plasmid alone was at least as effective as complexes of DNA with lipid. Measurements of vector-specific CFTR transcripts also showed gene transfer with both DNA-lipid and DNA alone. These results indicate that nonviral vectors can transfer CFTR cDNA to airway epithelia and at least partially restore the Cl- transport defect characteristic of CF. However, improvements in the overall efficacy of gene transfer are required to develop a treatment for CF.

Adolescent↗

PubMed1996

Estradiol induces E-cadherin degradation in mouse uterine epithelium during the estrous cycle and early pregnancy.

Mouse uterine epithelium is a tissue that undergoes cyclic endocrine-regulated cell dissociation and regeneration. It shows a dramatic cell loss following normal estrus. If pregnancy ensues, cell loss is averted during the first 2.5-3.5 days. However, this is followed by a precipitous loss of basal-lateral cell adhesion and apoptosis in preparation for blastocyst invasion. By comparing epithelia isolated by protease treatment, we show that a reduction of lateral cell adhesion is a primary event in these instances of normal tissue loss. It was readily induced in ovariectomized adult and immature mice by injections of estradiol (E2), and to some extent also by progesterone (P4). The reduction of lateral adhesion induced by including ethylene glycol-bis (beta-aminoethyl ether) -N,N,N',N'-tetraacetic acid (EGTA) in the isolation medium mimicked and was additive to the effect of E2 injection. However, the E2 effect was different in not being prevented by adding Ca2+. The E2 effect also was mimicked by the action on isolated epithelium of monoclonal antibody against the calcium-dependent cell adhesion molecule, E-cadherin, suggesting that inactivation of E-cadherin was induced by E2. In detergent extracts of estrous and metestrous epithelium there was an increase in 80-kDa extracellular domain of E-cadherin relative to the intact 120-kDa molecule. The loss of adhesion between 3.5 and 4.5 days of pregnancy was associated with a loss of both intact membrane-associated 120-kDa E-cadherin and cleavage products. Cleavage of 80-kDa E-cadherin was uniquely induced by E2 in ovariectomized adult and immature mice; P4 was without effect. The cleavage of E-cadherin correlated with increased basal accumulation of E-cadherin antigen in estrous and E2-injected mice and a loss of both basal and lateral antigen at 4.5 days of pregnancy. Only the E-cadherin antigen within junctional complexes appeared unaffected. The data are consistent with the hypothesis that the cyclic and pregnancy-dependent disruption of uterine epithelial integrity are promoted by E2-dependent modification of E-cadherin, including its extracellular cleavage.

Animals↗

PubMed1996

Exposure to 60 Hz magnetic fields does not alter clinical progression of LGL leukemia in Fischer rats.

Associations between exposure to 60-Hz magnetic fields in residential and occupational environments and the incidence of leukemia and other cancers has been suggested by the results of a number of epidemiology studies. To address these potential associations, a study has been conducted to determine if 60-Hz magnetic fields can alter the clinical progression of leukemia. In the large granular lymphocytic (LGL) leukemia model, spleen cells from aged leukemic rats were transplanted into young, male Fischer 344 rats, producing leukemia in a relatively short period. A total of 72 animals were randomly assigned to four treatment groups (18/group) as follows: (1) 10 G; (2) sham exposed (null energized field) (approximately 20 mG); (3) ambient controls (<1 mG); and (4) positive controls (5 Gy whole body irradiation from Cobalt-60, 4 days before initiation of exposure). At the initiation of exposure or sham-exposure, all rats were injected (i.p.) with 2.2x10(7) fresh, viable, LGL leukemia cells. The magnetic fields were activated for 20 h per day, 7 days per week; all exposure conditions were superimposed over the natural ambient magnetic field. Eighteen rats from each treatment were bled at weeks 0, 2, 4, 5, 6, 7, 8 and 10 to monitor, in the same set of animals, the clinical progression of the LGL disease and survival of the animals. Peripheral blood hematological changes were monitored to evaluate the progression of the leukemia. In general, no significant or consistent differences were detected between the magnetic field exposed and the ambient field control groups, although some inconsistent and random differences were occasionally observed. These data indicate that the 10 G magnetic fields did not significantly alter the clinical progression of LGL leukemia in Fischer 344 rats.

Animals↗

PubMed1994

Estradiol-17 beta stimulates proliferation of uterine epithelial cells cultured with stromal cells but not cultured separately.

There is indirect evidence that the in vivo proliferative response of rodent uterine epithelium to estrogen requires interaction with the underlying stroma in pre- and post-pubescent animals. To examine this potential requirement directly, the proliferative response of epithelium to 17 beta-estradiol in the presence or absence of stroma was measured in vitro. Uterine epithelial and stromal cells were isolated separately from immature or adult mice, and were maintained as monocultures or cocultures in defined, serum-free medium with or without 8 x 10(-9) M 17 beta-estradiol. Incorporation of bromodeoxyuridine into the DNA was determined by immunolabeling to assay proliferation in individual cells. Cell morphology and immunolabeling of cytokeratin were used to distinguish epithelial from stromal cells. Treatment of cocultures with 17 beta-estradiol for 24 h increased the proliferation of epithelial cells relative to controls approximately threefold, whereas, in monocultures of epithelial or stromal cells 17 beta-estradiol decreased the number of bromodeoxyuridine-incorporating cells by approximately half. Furthermore, cell contact between epithelial and stromal cells was important for the effects of 17 beta-estradiol on cells in cocultures. Approximately three quarters of the 17 beta-estradiol-induced proliferation of epithelial cells in cocultures was produced by epithelial cells within colonies that were also contacting stromal cells. These results are consistent with the hypothesis that stromal cells mediate the estrogenic proliferative response, and provide evidence that this mediation involves cell contact or stroma-mediated changes in the microenvironment immediately around the epithelial cell.

Animals↗

PubMed1994

Specific stimulation of basal lamina heparan sulfate proteoglycan in mouse uterine epithelium by Matrigel and by transforming growth factor-beta 1.

The basal lamina of differentiated epithelium normally turns over only slowly unless stimulated by tissue repair and growth. We show here that one mechanism of this stimulation, as modeled by basal lamina proteoglycan synthesis, may be the release of basal lamina-bound transforming growth factor (TGF-beta). A large heparan sulfate proteoglycan (HSPG, 0.2 Kav on Sepharose CL-4B) that was extractable from mouse uterine epithelium with 4 M guanidine-HCl or 1 M KCl was recognized by a specific monoclonal antibody to the basal lamina HSPG, perlecan. This HSPG was metabolically inactive with respect to [35S]-sulfate labeling in pieces of whole uterus during 4 h of culture, but it was labeled in isolated cells under the same conditions, provided that the cells had been cultured at least 6 to 12 h before labeling. The rate of labeling was then constant during at least 4 days in culture in serum-containing medium. Cultures on Matrigel showed an enhanced [35S]-sulfate labeling specifically in the 0.2 Kav HSPG fraction. Partial stimulation was obtained with a serum-free medium extract of Matrigel, which fractionated on Sephadex G-50 in two components; a major one > 30 kDa and the other at about 15 to 25 kDa. The specific stimulation was mimicked by the addition of 10 ng/ml of TGF-beta 1, but there was no specific stimulation by basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), insulinlike growth factor-1 (IGF-1), or interleukin-1 (IL-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Distribution of heparan sulfate proteoglycans in embryonic chicken neural retina and isolated inner limiting membrane.

Quantitative distribution of proteoglycans was studied in retinal neural epithelium and its basement membrane (inner limiting membrane). Heparan sulfate proteoglycans (HSPGs) were primarily associated with both inner and outer plexiform (synaptic) layers, and inner limiting membrane (ILM), as determined by autoradiographs of lyase-digested cryosections. Based on distribution of 35S-sulfate-labeled proteoglycans, the isolated ILM contained on average approximately three fourths of its proteoglycans as HSPGs and one fourth as chondroitin sulfate/dermatan sulfate proteoglycans (CS/DSPGs), whereas the remaining retina contained approximately equal amounts of the two proteoglycans (PGs). Immunohistochemical staining indicates that the core proteins of the HSPGs in the ILM are distinct from those of the plexiform layers. The photoreceptor layer, which other studies have shown to contain much of the extracellular CS/DSPGs, was not examined. Enrichment of distinct HSPGs in the ILM and plexiform layers support the conclusion that the HSPGs may be intimately involved in the different developmental events characterizing the two regions: development and extension of ganglion cell axons in the former, synaptogenesis and neuronal function in the latter.

Animals↗

PubMed1994

Micronuclei induced by radon and its progeny in deep-lung fibroblasts of rats in vivo and in vitro.

Genotoxic damage induced by radon and its progeny was investigated using the micronucleus assay in deep-lung fibroblasts to compare the response induced in vitro with that induced from inhalation of radon and its progeny in vivo. Male Wistar rats were exposed to 0, 115, 213 and 323 working-level months (WLM) of radon and its progeny by inhalation. After sacrifice, the cells were isolated and grown in culture, and the frequency of micronuclei was determined. A linear increase in the frequency of micronuclei was measured as a function of exposure [micronuclei/1000 binucleated cells = (29 +/- 9) + (0.47 +/- 0.04) WLM]. To compare exposure in WLM to dose in mGy, and to study how cell proliferation influences the way inhalation of radon and its progeny induces micronuclei, lung fibroblasts were isolated and exposed in vitro to graded doses from radon and its progeny after either 16 or 96 h in tissue culture. Cell cycle stage at the time of exposure was determined using flow cytometry. Primary lung fibroblasts exposed as either nondividing or dividing cells showed dose-dependent increases in micronuclei [micronuclei/1000 binucleated cells = (33 +/- 40) + (593 +/- 68)D and micronuclei/1000 binucleated cells = (27 +/- 69) + (757 +/- 88)D, respectively, where D is dose in Gy]. Results showed no significant influence (P = 0.20) of cell proliferation at the time of exposure on the frequency of micronuclei induced by radon and its progeny. Comparing dose-response relationships for nondividing cells to the exposure response for cells exposed by inhalation of radon and its progeny, it was estimated that a 1-WLM exposure in vivo caused the same amount of cytogenetic damage as produced by 0.79 mGy in vitro. In vivo/in vitro research using the micronucleus assay in lung fibroblasts serves as a powerful tool to estimate effective dose to cells in the respiratory tract after inhalation of radon and its progeny. Such studies form the basis for understanding the relationship between exposure, dose and biological damage.

Administration, Inhalation↗

PubMed1993

Proteoglycans and the modulation of cell adhesion by steric exclusion.

The hypothesis that cell aggregation may be driven by linear polymers in the matrix, particularly glycosaminoglycans, is revisited in light of more recent evidence. A model is proposed that extends the concept of steric exclusion to include a role in determining the directionality of cell migration and neurite extension. Recent literature is reviewed to support the conclusion that in living tissues the theoretical conditions for driving aggregation and migration by steric exclusion are met. The ability of a linear polymer to exclude cells is a function of its viscosity, which is optimum with glycosaminoglycans similar to chondroitin sulfate. It is ineffective with low viscosity glycosaminoglycans such as most heparin or heparan sulfate. Hyaluronic acid, a massive polymer, excludes cells poorly when present as an open matrix gel but forms an effective exclusion barrier when attached to the cell surface. According to a model for steric exclusion in organogenesis, when cells have a glycocalyx of linear polymer, they should disperse and migrate down a viscosity gradient of excluding matrix polymer; when they shed or internalize their surface coat in the continued presence of matrix, they should be excluded into a smaller volume and thus stimulated to aggregate.

Animals↗

PubMed1993

Molecular confirmation of alpha 1-antitrypsin genotypes in newborn dried blood specimens.

Deficiency of alpha 1-antitrypsin (alpha 1AT), a common hereditary disorder of Caucasians, is associated with an increased risk for early-onset chronic obstructive pulmonary disease and childhood liver dysfunction. The two most common deficiency variants, PiS and PiS, are both single base-pair substitutions causing amino acid modifications, although neither mutation creates or destroys a naturally occurring restriction site. Dried blood specimens (DBS) submitted to the New York State Department of Health for mandated newborn screening tests were tested for alpha 1AT activity using a fluorometric elastase inhibition assay. A second DBS from specimens determined to be alpha 1AT deficient was phenotyped on an agarose isoelectric focusing gel. Genotypic confirmation was performed by amplifying, directly from a DBS, the regions of the DNA containing the S and Z mutation. The Z mutation was analyzed with a modified primer designed to create an artificial restriction site in the normal allele. TaqI digestion produces two bands, a 157- and a 22-bp fragment. The single base substitution in PiS individuals eliminates this TaqI restriction site, thus showing the same 179-bp fragment before and after digestion. A primer mismatch placed close to the S mutation creates a restriction site in the normal allele, producing a 100-bp product after TaqI digestion. The restriction site is abolished in individuals that carry the S mutation, with a 121-bp product observed before and after digestion. Of 11,081 specimens screened, 3 PiS neonates, all Caucasian, were detected by these methodologies for an estimated incidence of 1:2019 in the Caucasian or 1:3694 in the general population in New York State.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

PubMed1992

Immunophenotypic characterization of owl monkey peripheral blood mononuclear cells.

A two-phase study was initiated to delineate the peripheral blood lymphocyte populations present in owl monkeys and to correlate those populations with immune response and parasitism during malaria infection. The goal of phase I of the study was to elucidate a monoclonal antibody panel that could be used to characterize peripheral blood mononuclear cell (PBMC) populations with flow cytometric techniques. Forty-two monoclonal antibodies (reported to be reactive with human and macaque lymphocyte antigens) were screened for activity to owl monkey PBMC. Eleven monoclonals were found to react: anti-H42A (MHC Class II DP-like); anti-TH14B (MHC Class II DR-like); and anti-TH81A5 (MHC Class II DQ-like); anti-H58A (MHC Class I); anti-DH59B (granulocyte and monocyte); anti-B1 (B cell); anti-T4 (CD4); anti-Leu3a (CD4); anti-Leu11a (CD16); anti-60.3 (CD18); and anti-OKM1 (NK and monocyte). In a preliminary retrospective study correlating antibody titers, parasitemia values, and MHC Class I and Class II marker profiles on PBMC to test antigens used in malaria vaccine trials, a significant negative association was observed between cells bearing MHC Class II molecules and the other elements of the comparison. In summary, an appropriate panel of monoclonal antibodies has been identified for characterizing PBMC in owl monkeys, and preliminary studies indicate a possible association between clinical outcome and expressed phenotypic PBMC markers.

Animals↗

PubMed1992

Changes in histochemical distribution of cell surface heparan sulfate proteoglycan in mouse uterus during the estrous cycle and early pregnancy.

We have investigated the changes in immunolocalization of a cell surface heparan sulfate proteoglycan (HSPG) in the mouse uterus during the estrous cycle and at the time of implantation in early pregnancy. A monoclonal antibody prepared against syndecan, a cell surface HSPG from mouse mammary epithelium (gift of Dr. M. Bernfield), was reacted with unfixed and fixed frozen sections of uteri from normally cycling, 3.5 and 4.5 days pregnant, and estradiol-treated immature and ovariectomized mature mice. A polyclonal antibody prepared against basal lamina HSPG from Engelbreth-Holm-Swarm (EHS) tumor cells (gift of Dr. John Hassell) was used as a positive control. The latter showed no variation during the estrous cycle or early pregnancy. Localization of syndecan in uterine epithelium changed from basolateral to predominantly basal as the cycle progressed from metestrus toward estrus. A similar pattern was seen in immature and ovariectomized mature females that had received estradiol injections. With the onset of pregnancy, the basolateral localization became progressively less intense from 3.5 days through 4.5 days of pregnancy. Thus, cell surface HSPG distribution is modulated by hormonally dependent changes in cycling and pregnant mice, supporting previous suggestions that early pregnancy in mice is accompanied by a turnover and rearrangement of uterine epithelial cell surface.

Animals↗

PubMed1991

Evaluation of changes in diatom mobility after exposure to 16-Hz electromagnetic fields.

The effect of a 16-Hz electromagnetic field on the mobility of the diatom Amphora coffeaformis was examined on agar plates that contained no added calcium and also on agar plates containing 0.25 or 2.5 mM exogenous Ca2+. Exposure conditions consisted of an ac field of 16 Hz with an amplitude of 20.9 microT parallel to the horizontal component of the dc field (BH = 20.9 microT, where BV = 0). To assess results, the percentage of diatoms that moved a distance greater than their body length was determined. We observed the field-associated increase in diatom motion at 0.25 mM Ca++, which was previously reported in the literature. Although the magnitude of the effect at 16 Hz was significant, the percentage of cells that moved was not sufficiently reproducible to allow examination for frequency dependence.

Calcium↗

PubMed1990

Exposure of mammalian cells to 60-Hz magnetic or electric fields: analysis of DNA repair of induced, single-strand breaks.

DNA damage was induced in isolated human peripheral lymphocytes by exposure at 5 Gy to 60Co radiation. Cells were permitted to repair the DNA damage while exposed to 60-Hz fields or while sham-exposed. Exposed cells were subjected to magnetic (B) or electric (E) fields, alone or in combination, throughout their allotted repair time. Repair was stopped at specific times, and the cells were immediately lysed and then analyzed for the presence of DNA single-strand breaks (SSB) by the alkaline-elution technique. Fifty to 75 percent of the induced SSB were repaired 20 min after exposure, and most of the remaining damage was repaired after 180 min. Cells were exposed to a 60-Hz ac B field of 1 mT; an E field of 1 or 20 V/m; or combined E and B fields of 0.2 V/m and 0.05 mT, 6 V/m and 0.6 mT, or 20 V/m and 1 mT. None of the exposures was observed to affect significantly the repair of DNA SSB.

Cobalt Radioisotopes↗

PubMed1990

An outbreak of foodborne botulism associated with contaminated hazelnut yoghurt.

The largest recorded outbreak of foodborne botulism in the United Kingdom occurred in June 1989. A total of 27 patients was affected; one patient died. Twenty-five of the patients had eaten one brand of hazelnut yoghurt in the week before the onset of symptoms. This yoghurt contained hazelnut conserve sweetened with aspartame rather than sugar. Clostridium botulinum type B toxin was detected in a blown can of hazelnut conserve, opened and unopened cartons of hazelnut yoghurt, and one faecal specimen. Cl. botulinum type B was subsequently cultured from both opened and unopened cartons of the hazelnut yoghurt and from one faecal specimen. Investigations indicated that the processing of the conserve was inadequate to destroy Cl. botulinum spores. Control measures included the cessation of all yoghurt production by the implicated producer, the withdrawal of the firm's yoghurts from sale, the recall of cans of the hazelnut conserve, and advice to the general public to avoid the consumption of all hazelnut yoghurts.

Adolescent↗

PubMed1990

Evidence for an effect of ELF electromagnetic fields on human pineal gland function.

A study was carried out to determine possible effects of 60-Hz electromagnetic-field exposure on pineal gland function in humans. Overnight excretion of urinary 6-hydroxymelatonin sulfate (6-OHMS), a stable urinary metabolite of the pineal hormone melatonin, was used to assess pineal gland function in 42 volunteers who used standard (conventional) or modified continuous polymer wire (CPW) electric blankets for approximately 8 weeks. Volunteers using conventional electric blankets showed no variations in 6-OHMS excretion as either a group or individuals during the study period. Serving as their own controls, 7 of 28 volunteers using the CPW blankets showed statistically significant changes in their mean nighttime 6-OHMS excretion. The CPW blankets switched on and off approximately twice as often when in service and produced magnetic fields that were 50% stronger than those from the conventional electric blankets. On the basis of these findings, we hypothesize that periodic exposure to pulsed DC or extremely low frequency electric or magnetic fields of sufficient intensity and duration can affect pineal gland function in certain individuals.

Adult↗