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Biomedical subjects

M A Franklin

Publications and source records attributed to M A Franklin.

14 recordsLinked to original sources

Bastadin 20 and bastadin O-sulfate esters from Ianthella basta: novel modulators of the Ry1R FKBP12 receptor complex.

New compounds bastadin 20 (9), 15,34-O-disulfatobastadin 7 (10), and 10-O-sulfatobastadin 3 (11) were isolated from Ianthella basta collected in Exmouth Gulf, Western Australia. Compounds 10 and 11 exhibited moderate differential activity as SR Ca2+ channel agonists (EC50 13.6 and 100 microM, respectively) of the Ry1R FKBP12 complex, while the potency of 9 was almost half that of 10 (EC50 20.6 microM). The problem of dereplication of bastadins was addressed using 1H-NMR "fingerprinting" of MeO signals in the corresponding permethyl bastadin derivatives.

Animals

A PCR-based method of detection and differentiation of K88+ adhesive Escherichia coli.

The objective of this study was to develop a polymerase chain reaction (PCR)-based method to detect and differentiate among Escherichia coli strains containing genes for the expression of 3 antigenic variants of the fimbrial adhesin K88 (K88ab, K88ac, and K88ad). Five primers were designed that allowed detection of K88+ E. coli, regardless of antigenic variant, and the separate detection of the ab, ac, and ad variants. Primers AM005 and AM006 are 21 base pair (bp) oligomers that correspond to a region of the K88 operon that is common to all 3 antigenic variants. Primers MF007, MF008, and MF009 are 24-bp oligomers that matched variable regions specific to ab, ac, and ad, respectively. Using primers AM005 and AM006, a PCR product was obtained that corresponds to a 764-bp region within the large structural subunit of the K88 operon common to all 3 antigenic variants. Primer AM005 used with MF007, MF008, or MF009 produced PCR products approximately 500-bp in length from within the large structural subunit of the K88 operon of the 3 respective antigenic variants. Fragments were identified by rates of migration on a 1% agarose gel relative to each other as well as to BstEII-digested lambda fragments. This PCR-based method was comparable to the enzyme-linked immunosorbent assay and western blot test in the ability to differentiate between the antigenic variants. K88+ E. coli were differentiated from among laboratory strains and detected in ileal samples taken from cannulated pigs challenged with a known K88+ variant. K88+ E. coli were also detected from fecal swabs taken from newly weaned pigs, thus confirming that this PCR-based test could provide a convenient clinical assay for the detection of K88+ E. coli. Detection and differentiation of K88+ E. coli using general and specific primers was successful. PCR methods of detection should permit identification of K88+ antigenic variants regardless of the level of expression of the antigen.

Adhesins, Escherichia coli

Testing and validation of computerized decision support systems.

Systematic, through testing of decision support systems (DSSs) prior to release to general users is a critical aspect of high quality software design. Omission of this step may lead to the dangerous, and potentially fatal, condition of relying on a system with outputs of uncertain quality. Thorough testing requires a great deal of effort and is a difficult job because tools necessary to facilitate testing are not well developed. Testing is a job ill-suited to humans because it requires tireless attention to a large number of details. For these reasons, the majority of DSSs available are probably not well tested prior to release. We have successfully implemented a software design and testing plan which has helped us meet our goal of continuously improving the quality of our DSS software prior to release. While requiring large amounts of effort, we feel that the process of documenting and standardizing our testing methods are important steps toward meeting recognized national and international quality standards. Our testing methodology includes both functional and structural testing and requires input from all levels of development. Our system does not focus solely on meeting design requirements but also addresses the robustness of the system and the completeness of testing.

Artificial Intelligence

Exact mass determination for elemental analysis of ions produced by matrix-assisted laser desorption.

The exact masses of bastadins, cyclic peptides from marine sponges Ianthella basta, are determined using matrix-assisted laser desorption ionization (MALDI) coupled to a Fourier transform mass spectrometer. Two known compounds were mixed with the unknown to serve as internal calibrants. The mass of the calibrants bracketed the mass of the unknown compound. With this method, exact masses were obtained to within 5 ppm for single determinations, and less than 3 ppm for multiple determinations, allowing the derivation of elemental composition. This method is viable for routinely obtaining the exact masses of new compounds with MALDI.

Animals

Medical informatics academia and industry: a symbiotic relationship that may assure survival of both through health care reform.

There are often clear lines drawn identifying the demilitarized zone between medical informatics academics and industry. Academics were "pure" intellectuals sequestered in ivory towers that effectively shielded them from the realities of the world. Industry has historically focused on creating effective products that produce financial return to the corporation. Both the paradigms of academia and industry are quickly becoming dinosaurs in the era of health care reform where both medical informatics academia and industry are under increasing pressure to develop and prove that medical informatics has a positive impact on health care both in terms of the quality of care as well as cost. Unfortunately, neither academia or industry alone are going to be able to successfully complete this task. The purpose of this paper is to describe such a collaborative effort that has produced a computerized decision support system for the management of mechanical ventilation in patients with the Adult Respiratory Distress Syndrome (ARDS) that is now installed and supported on three different commercial CIS platforms. This collaborative effort has allowed us to successfully mount a large multi-center clinical trial designed to determine efficacy.

Clinical Protocols

Effect of creep feeding on selected microflora and short-chain fatty acids in the ileum of weanling pigs.

Pigs cannulated at the ileum were used to investigate the effect of creep feeding on specific intestinal microflora and VFA and lactate concentrations. In two replicate trials performed 50 d apart, a total of 24 15-d-old nursing pigs from seven sows were cannulated in the terminal ileum and randomly assigned to two test groups. One group was allowed access to a creep diet, whereas the other group was denied access to the diet by removal from the farrowing crate. Ileal samples were collected at 19, 22, 26, and 29 d of age (preweaning) and at 33, 36, and 40 d of age (postweaning). Samples were assayed for total and hemolytic E. coli, total lactobacilli, pH, acetate, propionate, butyrate, isobutyrate, valerate, isovalerate, D(-), and L(+) lactate. Creep feeding did not affect lactobacilli or E. coli concentrations (P > .05), nor did it affect short-chain fatty acid concentrations (P > .05). Most volatile fatty acid concentrations decreased (P < .05), total lactate increased (P < .05), and the proportion of E. coli that were hemolytic increased (P < .05) following weaning. Consumption of creep feed did not affect specific microbial populations or fermentative byproducts in the ileum of the young pig.

Animal Feed

Synthesis of 5-substituted isophthalic acids and competitive inhibition studies with bovine liver glutamate dehydrogenase.

Isophthalic acid, 5-carboxy-, 5-hydroxy-, 5-methoxy-, 5-fluoro-, 5-bromo-, 5-cyano-, and 5-methylisophthalic acid were inhibitors competitive with L-glutamate for bovine liver glutamate dehydrogenase. The extent of inhibition by the derived compounds was not much greater than that obtained with the parent compound, isophthalic acid. A plot of pKi versus pH showed the presence of an ionizable group (pKa 7.4-7.8) at the enzyme active site which interacted with the substitutent at the 5 position of the substituted isophthalates.

Animals

Studies on natural gastric flora: survival of bacteria in fasting human subjects.

The present report deals with the survival of micro-organisms in the gastric lumen of fasting human subjects. Studies were carried out on hospitalized adult patients during the day, at night and over a 24-hour period.It is concluded that the survival of bacteria in the gastric lumen depends on the pH of the gastric juice. The duration of survival of the organisms at the pH <3.0 varied; however, at pH> 4.0, when a subsequent rapid drop in pH occurred, the clearing of viable organisms occurred within the hour sampling period in most cases. It is possible that medications which decrease gastric acidity favour an increase in the growth of gastric bacteria, while substances with a low pH may decrease bacterial growth.

Adult

Partial characterization of antigenic streptococcal plasma membrane components in acute glomerulonephritis.

Fluorescein-labeled immunoglobulin G (IgG) fractions of serum from patients with acute poststreptococcal glomerulonephritis stained parts of the glomerular basement membrane and mesangium of kidney tissue obtained from the same patients during the early phase of the disease. Renal tissue obtained from normal individuals and from patients with other kidney diseases failed to stain with these IgG fractions. Preabsorption of the serum fractions with various freezethawed bacteria demonstrated that only certain group A streptococci abolished the staining capacity. Fractionation of the streptococci into cellular constituents indicated that it was predominantly the plasma membrane fraction which blocked the immune staining. Spectrofluorometry using alkali-solubilized renal tissue confirmed these observations in a quantitative manner. By sucrose density-gradient ultracentrifugation of the plasma membrane two possible antigens were isolated. One was soluble in phosphate-buffered saline and the other was insoluble. The soluble component was a lipoprotein with a molecular weight of approximately 120,000.

Adult

Studies on natural gastric flora. I. Bacterial flora of fasting human subjects.

The presence and survival of ingested micro-organisms, both pathogenic and commensal, is of practical interest because the stomach is one of the principal portals of entry of bacteria in humans. A study of the environmental factors governing the survival of indigenous flora in the gastric lumen will assist in determining whether potentially pathogenic organisms will survive in the stomach and pass on. The authors set out to determine the significance of gastric mucin in such survival, with the ultimate objective of learning what factors provide optimal bactericidal conditions.Samples of gastric juice were aspirated from 149 fasting individuals; samples of saliva, nose and throat swabs were also obtained. Positive gastric cultures were found in 82%. The study of the effects of gastric pH demonstrated an increase in the number of samples showing growth above pH 2.0 and a concomitant increase in total bacterial growth. At a pH lower than 2.0, certain organisms are selected out. It appears that even minor changes in gastrointestinal physiology disrupt the normal clearing of the flora.

Adolescent