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Biomedical subjects

K M Morgan

Publications and source records attributed to K M Morgan.

17 recordsLinked to original sources
PubMed2001

An experimental and computational study of 1,2-hydrogen migrations in 2-hydroxycyclopentylidene and its conjugate base.

Thermal decomposition of alpha-hydroxydiazirine 2 gives primarily cyclopentanone and some allylic alcohol, in similar amounts as the known cyclohexyl analogue 1. Calculations (B3LYP/6-31+G) also show cyclopentanone to be the major product of this carbene rearrangement. Diazirine 2 and the lithium salt of the corresponding conjugate base 3 were decomposed by photolysis. The proportion of ketone formed increases with deprotonation, a trend also found computationally. In comparison, the base-induced isomerization of cyclopentene oxide, which proceeds via alpha-elimination to a carbenoid intermediate similar to that obtained from 3, yields primarily allylic alcohol rather than ketone; neither ring size nor charge thus accounts for the unusual product distribution observed. Interestingly, the calculations reveal that in the gas phase with no counterion, the singlet, oxyanionic carbene, and the alpha-deprotonated epoxide are the same, rather than discrete structures. This intramolecular complexation stablilizes the oxyanionic carbene by 20-25 kcal/mol.

Journal Article↗
PubMed2001

A deliberative method for ranking risks (I): Overview and test bed development.

Risk ranking offers a potentially powerful means for gathering public input to help set risk-management priorities. In most rankings conducted to date, the categories and attributes used to describe the risks have varied widely, the materials and procedures have not been designed to facilitate comparisons among risks on all important attributes, and the validity and reproducibility of the resulting rankings have not been assessed. To address these needs, a risk-ranking method was developed in which risk experts define and categorize the risks to be ranked, identify the relevant risk attributes, and characterize the risks in a set of standardized risk summary sheets, which are then used by lay or other groups in structured ranking exercises. To evaluate this method, a test bed involving 22 health and safety risks in a fictitious middle school was created. This article provides an overview of the risk-ranking method and describes the challenges faced in designing the middle school test bed. A companion article in this issue reports on the validity of the ranking procedures and the level of agreement among risk managers regarding ranking of risks and attributes.

Adolescent↗
PubMed2001

A deliberative method for ranking risks (II): Evaluation of validity and agreement among risk managers.

A deliberative method for ranking risks was evaluated in a study involving 218 risk managers. Both holistic and multiattribute procedures were used to assess individual and group rankings of health and safety risks facing students at a fictitious middle school. Consistency between the rankings that emerged from these two procedures was reasonably high for individuals and for groups, suggesting that these procedures capture an underlying construct of riskiness. Participants reported high levels of satisfaction with their groups' decision-making processes and the resulting rankings, and these reports were corroborated by regression analyses. Risk rankings were similar across individuals and groups, even though individuals and groups did not always agree on the relative importance of risk attributes. Lower consistency between the risk rankings from the holistic and multiattribute procedures and lower agreement among individuals and groups regarding these rankings were observed for a set of high-variance risks. Nonetheless, the generally high levels of consistency, satisfaction, and agreement suggest that this deliberative method is capable of producing risk rankings that can serve as informative inputs to public risk-management decision making.

Adolescent↗
PubMed2000

Modified amino acids and peptides as substrates for the intestinal peptide transporter PepT1.

The binding affinities of a number of amino-acid and peptide derivatives by the mammalian intestinal peptide transporter PepT1 were investigated, using the Xenopus laevis expression system. A series of blocked amino acids, namely N-acetyl-Phe (Ac-Phe), phe-amide (Phe-NH2), N-acetyl-Phe-amide (Ac-Phe-NH2) and the parent compound Phe, was compared for efficacy in inhibiting the uptake of the peptide [3H]-D-Phe-L-Gln. In an equivalent set of experiments, the blocked peptides Ac-Phe-Tyr, Phe-Tyr-NH2 and Ac-Phe-Tyr-NH2 were compared with the parent compound Phe-Tyr. Comparing amino acids and derivatives, only Ac-Phe was an effective inhibitor of peptide uptake (Ki = 1.81+/- 0.37 mM). Ac-Phe-NH2 had a very weak interaction with PepT1 (Ki = 16.8+/-5.64 mM); neither Phe nor Phe-NH2 interacted with PepT1 with measurable affinity. With the dipeptide and derivatives, unsurprisingly the highest affinity interaction was with Phe-Tyr (Ki = 0.10+/-0.04 mM). The blocked C-terminal peptide Phe-Tyr-NH2 also interacted with PepT1 with a relatively high affinity (Ki = 0.94+/-0.38 mM). Both Ac-Phe-Tyr and Ac-Phe-Tyr-NH2 interacted weakly with PepT1 (Ki = 8.41+/-0.11 and 9.97+/-4.01 mM, respectively). The results suggest that the N-terminus is the primary binding site for both dipeptides and tripeptides. Additional experiments with four stereoisomers of Ala-Ala-Ala support this conclusion, and lead us to propose that a histidine residue is involved in binding the C-terminus of dipeptides. In addition, a substrate binding model for PepT1 is proposed.

Amino Acids↗
PubMed1999

Retrospective analysis of an implant system.

The reliability of dental implants results from a combination of design, placement, and reconstructive techniques. Retrospective analysis is one vehicle for evaluating implant success. This article presents the reliability of these techniques in Bicon dental implants. The survivability of this implant was evaluated retrospectively using life table survival analysis over a 10-year period in 13 practices. The parameters used for success included no implant loss, no mobility, no continuing bone loss that did not stabilize after 1 year, no discomfort, and no purulence.

Dental Abutments↗
PubMed1998

4-aminomethylbenzoic acid is a non-translocated competitive inhibitor of the epithelial peptide transporter PepT1.

1. 4-Aminomethylbenzoic acid, a molecule which mimics the special configuration of a dipeptide, competitively inhibits peptide influx in both Xenopus Laevis oocytes expressing rabbit PepT1 and through PepT1 in rat renal brush border membrane vesicles. 2. This molecule is not translocated through PepT1 as measured both by direct HPLC analysis in PepT1-exp ressing oocytes and indirectly by its failure to trans-stimulate labelle d peptide efflux through PepT1 in oocytes and in renal membrane vessicle s. 3. However 4-aminiomethylbenzoic acid does reverse trans-stimulation through expressed PepT1 of labelled peptid efflux induced by unlabelled peptide. Quantitatively this reversal is compatible with 4-aminomethyl benzoic acid competitively binding to the external surface of PepT1. 4. 4-Aminomethylbenzoic acid (the first molecule discovered to be a non-translocated competitive inhibitor of proton-coupled oligopeptide transport) and its derivatives may thus be particularly useful as experimental tools.

4-Aminobenzoic Acid↗
PubMed1998

Peptide mimics as substrates for the intestinal peptide transporter.

4-Aminophenylacetic acid (4-APAA), a peptide mimic lacking a peptide bond, has been shown to interact with a proton-coupled oligopeptide transporter using a number of different experimental approaches. In addition to inhibiting transport of labeled peptides, these studies show that 4-APAA is itself translocated. 4-APAA transport across the rat intact intestine was stimulated 18-fold by luminal acidification (to pH 6.8) as determined by high performance liquid chromatography (HPLC); in enterocytes isolated from mouse small intestine the intracellular pH was reduced on application of 4-APAA, as shown fluorimetrically with the pH indicator carboxy-SNARF; 4-APAA trans-stimulated radiolabeled peptide transport in brush-border membrane vesicles isolated from rat renal cortex; and in Xenopus oocytes expressing PepT1, 4-APAA produced trans-stimulation of radiolabeled peptide efflux, and as determined by HPLC, was a substrate for translocation by this transporter. These results with 4-APAA show for the first time that the presence of a peptide bond is not a requirement for rapid translocation through the proton-linked oligopeptide transporter (PepT1). Further investigation will be needed to determine the minimal structural requirements for a molecule to be a substrate for this transporter.

Aniline Compounds↗
PubMed1997

African-American homeless and low-income housed mothers: comparison of parenting practices.

The child-rearing practices of homeless and low-income housed mothers of preschool children in Head Start were compared. Overall, homeless mothers provided less learning and academic stimulation, less variety in social and cultural experiences, less warmth and affection, and a less positive physical environment for their children than did housed mothers. Mothers in both living arrangements provided more language stimulation to daughters than to sons. Implications of the findings for working with homeless families are discussed.

Adult↗
PubMed1992

Candidal endophthalmitis after lithotripsy of renal calculi.

Candidal endophthalmitis is most commonly due to hematogenous seeding of the eye by Candida albicans. Although it is most often seen as a manifestation of disseminated candidiasis in patients who are seriously ill, other patients may have candidal endophthalmitis as the only evidence of fungal infection. We have presented a case of endophthalmitis due to C albicans in a patient who had bilateral renal calculi and who had received multiple antibiotics and extracorporeal shock wave lithotripsy.

Candidiasis↗
PubMed1990

Spontaneous involution of subfoveal neovascularization.

We studied five patients who maintained or spontaneously regained significant central vision despite the presence of a subfoveal neovascular membrane. Sequential photographs and fluorescein angiograms showed a pattern of development common to these patients and not observed in patients who lose all central vision. The pattern involves formation of a pigmented ring around the subfoveal neovascular membrane followed by alteration of the membrane from one that leaks fluorescein to one that stains but does not leak. This pattern is associated with gradual resorption of subretinal fluid and apparent limitation of subretinal hemorrhage and fibrosis. This course suggests the occurrence of spontaneous involution of some subfoveal neovascular membranes and implicates the retinal pigment epithelium in this process.

Adult↗
PubMed1989

Comparison of corneal storage in K-Sol and chondroitin sulfate corneal storage medium in human corneal transplantation.

Fifty-one pairs of corneas, stored in either K-Sol or CSM (chondroitin sulfate corneal storage medium) from 8 to 97 hours (mean +/- standard deviation, 58 +/- 21 and 57 +/- 21 hours, respectively), were transplanted in a prospective, randomized manner into 99 patients (n = 102 eyes), paired by diagnostic group and procedure. Ninety-six percent of K-Sol grafts (n = 51) and 94% of the CSM grafts (n = 51) were clear at 6 months; 92% of both the K-Sol (n = 38) and CSM (n = 35) grafts were clear at 12 months. One primary donor failure occurred, a K-Sol cornea stored for 76 hours. The CSM group experienced a greater number of persistent epithelial defects beyond 2 weeks (7 versus 4 defects) and graft reaction episodes (7 versus 3 episodes) than the K-Sol group; however, an equal number of late graft failures (3) occurred in both groups. No significant differences by paired t test analyses were found in endothelial cell density, area, coefficient of variation, or figure coefficient at 3 (n = 37 pairs), 6 (n = 36 pairs), and 12 (n = 26 pairs) months between the two groups. Mean endothelial cell density significantly decreased by 11% +/- 22 by 3 months in the K-Sol group, whereas the 7% +/- 24 decrease in the CSM group was insignificant. By 12 months, both groups experienced a significant decrease: K-Sol, 27% +/- 22; CSM, 17% +/- 26. A significant decrease in the mean coefficient of variation (polymegathism) was noted after 3 months in the K-Sol group which returned to the preoperative mean by 1 year, whereas this parameter remained unchanged in the CSM group. Both chondroitin sulfate-based media result in successful corneal transplantation with storage up to 4 days; however, endothelial survival with both media are comparable with previous studies with McCarey-Kaufman (M-K) medium.

Adolescent↗
PubMed1989

Sustained release of 5-fluorouracil from ethylene acetate copolymer.

Pharmacologic inhibition of fibroblast proliferation and scar formation remains an important consideration in many ophthalmologic surgical procedures. Such inhibition is particularly important in glaucoma filtration surgery. A sustained release system for 5-fluorouracil (5-FU) using ethylene vinyl acetate copolymer (Elvax) was characterized in vitro. 5-FU was incorporated into Elvax discs of 4 mm diameter. Discs were coated to allow sustained and predictable release over a 14 day period. Alteration of coatings, which act as rate-controlling membranes, allowed variation in the pattern of 5-FU release from the core which acts as the drug reservoir. This system for the sustained release of 5-FU may prove valuable in glaucoma surgery where the suppression of cellular proliferation is desired. The non-inflammatory nature of Elvax suggests this compound may provide an alternative means of 5-FU delivery.

Delayed-Action Preparations↗
PubMed1989

A donor-age-dependent change in the activity of alpha-mannosidase in human cultured RPE cells.

Six acidic glycosidase activities in cultured human retinal pigment epithelium (RPE) cells from donors of different ages (19 to 80 years) were studied with regard to pH optimum, Km, Vmax and specific activity. For alpha-mannosidase we found significant age-dependent decreases in specific activity and Vmax but not in Km. The other glycosidases and acid phosphatase, lactate dehydrogenase (LDH) and citrate synthase showed no change in these parameters with donor age. The alpha mannosidase activity of older donor cells could be activated almost 2-fold by the addition of zinc. This is the first report of age-dependent change in a human RPE lysosomal enzyme. Since alpha-mannosidase is probably required for the degradation of rhodopsin in the phagolysosomal system of the RPE, decrease in this enzyme activity may lead to accumulation of undigested rod outer segments (ROS) and drusen, both of which are associated with age-related macular degeneration (AMD).

Adult↗
PubMed1988

Lysosomal enzyme levels in corneal storage media. K-Sol versus McCarey-Kaufman.

Evidence indicates that lysosomal enzymes can carry out corneal autolysis during corneal storage and that they are damaging to the corneal endothelium. The authors investigated the release of lysosomal enzymes into two corneal storage media (K-Sol and McCarey-Kaufman [M-K]) by paired human donor corneas during 4 degrees C storage. The authors also studied the interaction of these media with lysosomal enzymes from human cornea. K-Sol and M-K stimulated (P less than 0.01) both beta-glucuronidase and alpha-galactosidase about equally. beta-N-Acetyl-glucosaminidase, a major catabolic enzyme of the cornea, was inhibited by the chondroitin sulfate in K-Sol by over 90% (P less than 0.01). Corneas stored in M-K released more lysosomal enzymes than corneas stored in K-Sol. At 4 days, the values approached significance (P less than 0.06) and by day 10 significantly higher values were found in the M-K media (P less than 0.01). Both storage methods showed a linear release. Individual corneas were found to vary in their release rates. Whether corneas that release more enzyme will show higher endothelial cell loss or produce less successful penetrating keratoplasty grafts deserves further study.

Chondroitin↗
PubMed1986

Beta-N-acetyl-glucosaminidase: possible role in ocular neovascularization.

The possibility that lysosomal enzymes might be involved as angiogenic factors in ocular neovascularization (NV) was investigated. Beta-N-acetyl-glucosaminidase (NAGase) activity, and that of two other glycosidases, were present in the retinal derived protein fraction (RDPF) reported by others to be angiogenic. NAGase, but not the other glycosidases, was inhibited by vitreous. NAGase exhibited the same stability characteristics as RDPF. In diabetic rats there was a significant rise in vitreous but a fall in retinal NAGase activity. The sera of these animals, however, showed elevation in the activities of all five glycosidases. Preliminary experiments indicate that only the intermediate isoenzyme of NAGase, putatively insulin dependent, is elevated in the eyes of these diabetic rats. NAGase was also specifically elevated in the intraocular fluid from monkey eyes with retinal vein occlusion (RVO), and markedly so if NV was present. These results suggest the involvement of NAGase in the neovascular process in the eye.

Acetylglucosaminidase↗