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Biomedical subjects

W S Johnson

Publications and source records attributed to W S Johnson.

At least 19 recordsLinked to original sources
PubMed2000

Colostrum and milk-derived peptide growth factors for the treatment of gastrointestinal disorders.

Colostrum is the specific first diet of mammalian neonates and is rich in immunoglobulins, antimicrobial peptides, and growth factors. In this article we review some of these constituents of human and bovine colostrum in comparison with those of mature milk. Recent studies suggest that colostral fractions, or individual peptides present in colostrum, might be useful for the treatment of a wide variety of gastrointestinal conditions, including inflammatory bowel disease, nonsteroidal antiinflammatory drug-induced gut injury, and chemotherapy-induced mucositis. We therefore discuss the therapeutic possibilities of using whole colostrum, or individual peptides present in colostrum, for the treatment of various gastrointestinal diseases and the relative merits of the 2 approaches.

Animals↗
PubMed1996

Cellular and extracellular remodeling with the development and recovery from tachycardia-induced cardiomyopathy: changes in fibrillar collagen, myocyte adhesion capacity and proteoglycans.

The myocardial extracellular matrix (ECM) is composed of three important constituents: (1) fibrillar collagen, (2) a basement membrane, and (3) proteoglycans. Structural or compositional changes in these ECM components may affect left ventricular (LV) function as well as influence overall LV geometry. Accordingly, this study examined the relationship between changes in these ECM components to changes in LV function and geometry which develop with the progression and regression from supraventricular tachycardia-induced cardiomyopathy (SVT). LV function and specific components of the ECM were studied in pigs with SVT cardiomyopathy (SVT:atrially paced 240 bpm, 3 weeks; n = 7), or after a 4-week recovery from SVT cardiomyopathy (post-SVT; n = 6), and in controls (n = 7). LV fractional shortening fell by 60% and end-diastolic dimension increased by 47% with SVT compared to controls. While LV fractional shortening normalized with post-SVT, end-diastolic dimension remained 40% higher than controls. Collagen concentration fell by 22% and salt extractable collagen, which reflects collagen cross-linking, increased by 41% with SVT compared to controls. Collagen concentration increased by 20%, collagen extraction normalized, and levels of collagen type III mRNA increased by 42% with post-SVT. Isolated myocyte adhesion capacity to basement membrane substrates laminin, fibronectin, and collagen type IV were examined. SVT resulted in over a 50% reduction in myocyte adhesion for all of the basement membrane components compared to controls. A normalization in isolated myocyte adhesion capacity was observed in post-SVT. The relative content and distribution of the ECM proteoglycan chondroitin sulfate was examined using immunohistochemistry. With SVT, the density of this proteoglycan increased around individual myocytes. With post-SVT, the relative distribution of chondroitin sulfate returned to control levels. Thus, SVT cardiomyopathy was associated with reduced collagen concentration and cross-linking, diminished myocyte basement membrane adhesion capacity, and increased proteoglycans. Recovery from SVT cardiomyopathy resulted in increased collagen concentration, and a normalization of myocyte adhesion capacity and proteoglycan distribution. These results suggest that changes within the ECM are a dynamic process and accompany the LV systolic and diastolic function as well as ventricular and myocyte remodeling during the progression and regression from cardiomyopathic disease.

Analysis of Variance↗
PubMed1996

Direct effects of chronic beta-adrenergic receptor blockade on left ventricular and myocyte function in a model of tachycardia-induced congestive heart failure.

BACKGROUND: Chronic beta-receptor blockade (beta-blockade) has been reported to improve symptoms and increase survival in patients with congestive heart failure (CHF); however, whether the mechanisms for the effects of beta-blockade in CHF are due to modulating chronotropy, inotropy, or both remains unknown. To address this issue, left ventricular function and isolated myocyte function were examined with chronic beta-blockade in a rapid pacing model of CHF, thereby eliminating potential chronotropic effects of beta-blockade. METHODS AND RESULTS: Pigs were randomly assigned to three groups of six pigs each: supraventricular tachycardia (SVT): 3 weeks of atrial pacing at 240 beats/min; SVT/beta-blockade: 3 weeks of rapid pacing and beta-blockade (25 mg atenolol twice daily on days 14-21 of pacing); control group, sham control animals. This dosage schedule for beta-blockade was chosen because catecholamines are persistently elevated by day 14 in this model of CHF. Left ventricular fractional shortening and end-diastolic dimension were measured by echocardiography in the conscious state with a resting ambient heart rate. Isolated left ventricular myocyte function was examined using high-speed videomicroscopy. Supraventricular tachycardia caused left ventricular dilation (5.4 +/- 0.1 vs 3.5 +/- 0.1 cm) and reduced fractional shortening (12 +/- 1% vs 35 +/- 1%) compared with control animals (P < .05). The SVT/beta-blockade group showed no significant effects on left ventricular size or function compared with the SVT group, but their ambient resting heart rate was reduced by 20% relative to the SVT group (P < .05). Myocyte shortening was reduced in the SVT group (2.2 +/- 0.1% vs 4.5 +/- 0.1%, P < .05) compared with the control group and increased from SVT-only values with beta-blockade (2.7 +/- 0.1%, P < .05). Similarly, myocyte shortening velocity was similarly reduced in the SVT and SVT/beta-blockade groups (31 +/- 1 and 32 +/- 1 microns/s) compared with the control group (51 +/- 1 microns/s, P < .05). With SVT/beta-blockade myocyte contraction duration was prolonged (525 +/- 5 ms) compared with SVT-only or control values (469 +/- 9 and 473 +/- 4 ms, P < .05). Thus, institution of beta-1-selective blockade during the development of SVT-induced CHF altered the temporal characteristics of the myocyte contraction process, which resulted in improved myocyte shortening. CONCLUSIONS: In a model of CHF due to the maintenance of a chronically elevated heart rate, institution of beta-1-selective blockade during the progression of the CHF process minimally affected left ventricular size and function. At the level of the myocyte, chronic beta-1-receptor blockade prolonged the contraction interval and thereby increased myocyte shortening. These unique results suggest that a contributory mechanism for the effects of beta-blockade in the setting of CHF is chronotropic modulation.

Adrenergic beta-Antagonists↗
PubMed1995

Selective recognition of the m5CpG dinucleotide sequence in DNA by mitomycin C for alkylation and cross-linking.

The clinically used natural antitumor agent mitomycin C (MC) is known to alkylate DNA monofunctionally and bifunctionally, resulting in the cross-linking of DNA. These reactions occur selectively with guanines at the CpG sequence. We show, confirming a previous report (Millard, J. T.; Beachy, T. M. Biochemistry 1993, 32, 12850) that cross-linking in oligonucleotides is further enhanced when the cytosines in CpG.CpG are 5-methylated to m5CpG.m5CpG. It is shown, furthermore, that guanines in m5CpG are monoalkylated two- to three-times faster than in CpG indicating that the m5C-induced rate enhancement occurs at the first, monoalkylation step of the two-step cross-linking process. The same MC-DNA adducts are formed in methylated as in non-methylated DNA. The basepaired but not the 5'-flanking, m5C residue is responsible for the enhanced alkylation of guanine. Enzymatically activated or Na2S2O4-activated MC shows identical rate-enhancement of alkylation at m5CpG. pBR322 DNA methylated by CpG-methylase was cross-linked two- to three-times more efficiently by MC than non-methylated DNA, indicating that the m5C effect is not an artifact of oligonucleotides. An electronic effect of the 5-methyl group of cytosine transmitted via G.C H-bonding to N2 of guanine is suggested as responsible for increased reactivity with MC. CpG is severely depleted in mammalian DNA and it is speculated that this factor attenuates MC cytotoxicity in human cells.

Alkylation↗
PubMed1994

The relation between latissimus dorsi skeletal muscle structure and contractile function after cardiomyoplasty.

Past reports suggest that structural changes within the latissimus dorsi muscle occur with chronic electrical stimulation during cardiomyoplasty. However, the specific changes in the structure of the latissimus dorsi muscle and the relation to muscle contractile function with cardiomyoplasty are unknown. Accordingly, this study examined regional changes in latissimus dorsi muscle structure and function after cardiomyoplasty. The left latissimus dorsi muscle was mobilized and wrapped around the heart in pigs with the use of standardized techniques and the latissimus dorsi muscle chronically paced at ambient heart rates (90 beats/min; 20 Hz, 5 V amplitude, n = 6). After 6 weeks, the paced latissimus dorsi muscle and the contralateral control muscle were removed and divided into proximal (0 to 3 cm), middle (3 to 6 cm), and distal (6 to 12 cm) regions. By computer-assisted morphometry, muscle cell myofibril volume, cross-sectional area, and collagen percent area were determined. In the paced latissimus dorsi muscle, myofibril volumes increased by more than 50% in the proximal and middle regions compared with those in the contralateral control muscle. However, myofibril volumes were significantly lower in the distal region of the paced latissimus dorsi muscle compared with those in control muscles (33% +/- 5% versus 20% +/- 3%, p < 0.05). In the paced latissimus dorsi muscle, cross-sectional area was significantly reduced from that of control muscles in all regions. A further reduction in cross-sectional area was noted in the distal region of the paced latissimus dorsi muscle compared with that in both the contralateral control muscle and the proximal and middle regions of the paced latissimus dorsi muscle. Collagen content significantly increased in the paced latissimus dorsi muscle compared with that in control muscle with a more fibrotic pattern observed in the distal region. Latissimus dorsi muscle strips (less than 2 mm2 cross-sectional area) were harvested, and peak and velocity of tension development were examined after field electrical stimulation at 0.2 to 1.2 Hz. At 0.2 Hz, the velocity of tension development was unchanged in the paced latissimus dorsi muscle compared with that in control muscle. However, peak tension development degraded by only 28% in the paced latissimus dorsi muscles but fell by 51% in control muscles with increased stimulation frequencies. In summary, the contractile function of the chronically stimulated latissimus dorsi muscle was associated with fatigue resistance and increased contractile protein content. However, more distal regions of the paced latissimus dorsi muscle demonstrated atrophy and fibrosis.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Orientation isomers of the mitomycin C interstrand cross-link in non-self-complementary DNA. Differential effect of the two isomers on restriction endonuclease cleavage at a nearby site.

Reductively activated mitomycin C (MC) forms DNA interstrand cross-links between two guanines at CG.CG sequences. It is predictable that such cross-links should occur in two isomeric strand orientations in duplex DNA (except when located in the center of a self-complementary duplex). This was verified by the isolation and characterization of a pair of two isomeric oligonucleotides in each case of five non-self-complementary duplexes of 8-bp length, cross-linked by MC. Isomer separation was accomplished by reverse-phase HPLC. The isomers in a pair were formed in approximately 1:1 proportion. Their structures were rigorously characterized by a two-step cross-linking procedure: first, 1''-monoalkylation of each strand, followed by conversion to a cross-linked duplex by annealing the monoalkylated strand to its complement in the presence of a reducing agent. The resulting individual authentic orientation isomers were used as standards for identification of the two isomers formed in the original (one-step) cross-linking reactions. A 16-bp duplex oligonucleotide was synthesized featuring the AluI cognate sequence, separated from a MC cross-link site by only 1 bp. Its two MC cross-linked isomers were prepared separately, and their rate of cleavage by AluI was determined using HPLC. Cleavage of both the unmodified and cross-linked duplexes was nonsymmetrical. The isomer in which the 2''-NH3+ of MC is oriented toward the AluI site was cleaved essentially at the same rate as the control duplex, while cleavage of the isomer with the MC indoloquinone group oriented toward the AluI site was inhibited 2-fold at the faster-cleaved strand.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1992

Inhibition of 2,3-oxidosqualene cyclases.

Monocyclic and tricyclic compounds possessing a nitrogen atom situated at a position corresponding to the carbenium ion of high energy intermediates or transition states involved during cyclization of 2,3-oxidosqualene to tetra- and pentacyclic triterpenes have been synthesized. These compounds were tested as inhibitors of 2,3-oxidosqualene cycloartenol, lanosterol-, and beta(alpha)-amyrin-cyclases in vitro and in vivo, and their affinity was compared to that of formerly synthesized 8-aza-bicyclic compounds [Taton et al. (1986) Biochem. Biophys. Res. Commun. 138, 764-770]. A monocyclic N-alkyl-hydroxypiperidine was shown to be the strongest inhibitor of the series upon cycloartenol-cyclase (I50 = 1 microM) from maize embryos but was much less effective on the beta(alpha)-amyrin-cyclases from Rubus fruticosus suspension cultures or pea cotyledons. In contrast, 13-aza-tricyclic derivatives displayed little inhibition on 2,3-oxidosqualene cycloartenol-, lanosterol-, and beta(alpha)-amyrin-cyclases. The obtained data exemplify the differences existing in the cyclization process between cycloartenol- (lanosterol-) cyclases on one hand and beta(alpha)-amyrin-cyclases on the other. The results are discussed with respect to current mechanisms postulated for 2,3-oxidosqualene cyclization. Because of its activity in vivo and in vitro the monocyclic N-alkyl-hydroxypiperidine appears to be a potent and promising tool to study sterol biosynthesis regulation.

Animals↗
PubMed1989

Cyanide poisoning successfully treated without 'therapeutic methemoglobin levels'.

A 24-year-old woman ingested an unknown amount of potassium cyanide in a suicide attempt. Coma and metabolic acidosis developed. Administration of the Lilly Cyanide Antidote kit (Eli Lilly and Co, Indianapolis) resulted in prompt resolution of symptoms and full recovery. Whole blood cyanide level was 13 micrograms/mL approximately one hour after ingestion. The highest measured methemoglobin level after sodium nitrite administration was 9.2%, demonstrating that attaining a "therapeutic methemoglobin level" of 25% is unnecessary to insure a satisfactory clinical outcome. Because severe hypotension or excessive methemoglobinemia can be caused by the sodium nitrite component of the Lilly kit, only enough to produce an acceptable clinical response should be administered.

Acidosis↗
PubMed1988

An evaluation of 9-aminoacridine/Gelfoam to reduce dry socket formation.

This clinical study was undertaken to evaluate the effectiveness of locally applied 9-aminoacridine in Gelfoam in reducing the incidence of dry socket formation after third molar extractions. Results indicated that this technique was not effective. The incidence of dry socket formation in smokers and nonsmokers was compared. Also, the influence of surgical trauma on dry socket formation was examined.

Aminacrine↗
PubMed1984

Rapid detection of methicillin-resistant staphylococci with the MS-2 system.

The ability of the updated Abbott MS-2 system to detect methicillin-resistant Staphylococcus aureus (MRSA) was compared with disk agar diffusion and broth microdilution. Of the 87 MRSA isolates tested, the MS-2 system correctly detected 85 (97.7%) in 5 h. Seventy-two of the isolates were detected by disk agar diffusion within 24 h, and 15 more by 48 h. Broth microdilution detected 71 MRSA by 24 h of incubation and 11 more by 48 h. The updated MS-2 system yielded reliable results that were highly comparable with the standard techniques.

Methicillin↗
PubMed1980

Some problems in assessing the physiological and economic significance of hypocupraemia in beef suckler herds.

Factors influencing the incidence of hypocupraemia and responses to copper therapy were investigated in three beef suckler herds calving in spring and early summer. On farm A hypocupraemia was most severe (plasma copper less than 0.4 mg per litre) in March for the cows and in October/November for their calves. On farm B plasma copper levels were 30 per cent lower in five to eight-year-old cows than in two-year-old cows in late November. Administration of copper (100 mg) in late pregnancy significantly increased plasma copper in the suckled calves on farm A but not in their dams after parturition. Growth of the calves was not increased. The alleviation of severe hypocupraemia on a third farm (C) by injecting the calf with copper did not improve growth rate. It is concluded that in some areas a severe seasonal hypocupraemia may be tolerated without loss of productivity.

Animal Feed↗
PubMed1980

Perception of verticality by boys and girls in grade 6.

Understanding of the principle of verticality was tested by having 246 sixth grade students draw a pendulum on pictures of an abstract shape similar to a steeple. Girls performed more poorly than boys. Verticality was apparently much better understood by subjects than horizontally, also tested to provide a comparison.

Child↗
PubMed1977

Effects of polyvinyl chloride ingestion by dogs.

Polyvinyl chloride (PVC) acrylic thermoplastic sheeting was fed to 6 dogs to determine whether ingestion during periods of normal transit of military working dogs would be toxic and thus affect the safety of this material for construction of shipping containers. The test dogs were fed PVC acrylic (0.125 g/kg of body weight; by gelatin capsule) twice each day for 5 days: for 2 dogs, the test material was in a shredded form; for 2 dogs, the material was diced; and for 2 dogs, it was powdered. Two other dogs were used as controls. Dogs were observed for clinical signs, and feed consumption and body weights were recorded. Blood and urine samples were examined. All animals were necropsied approximately 10 days after the feeding was stopped. Clinical or pathologic indication of a toxic effect of PVC was not seen within the time limits of the study.

Animals↗