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Biomedical subjects

C G Lewis

Publications and source records attributed to C G Lewis.

At least 37 records · Page 2Linked to original sources

Biotechnology and potential nutritional implications for children.

The tools of biotechnology have enormous potential to develop new, safe, and nutritious foods and food products that could benefit the immediate and long-term nutritional and health needs of the pediatric population. This is especially true as more emphasis is placed on the prevention, rather than the treatment, of chronic degenerative and metabolic diseases. But the promise of biotechnology for nutritional and health benefits of children's diets must be accepted with cautious optimism. Many advances in food technology and nutritional composition of food animals and plants have already been made through biotechnology, but they represent only the beginning of the necessary research. These advances have been based on relatively little knowledge of basic human nutritional needs, particularly during the dynamic pediatric period of growth and development. More importantly, these advances have been predicated with no understanding of dietary nutrient interactions. Changing nutrient composition of foods through biotechnology may alter nutrient interactions, nutrient-gene interactions, nutrient bioavailability, nutrient potency, and nutrient metabolism. Biotechnology has the potential to produce changes in our foods and in our diet at a pace far greater than our ability to predict the significance of those changes on pediatric nutrition. The Human Genome Project, which relies on biotechnology, will revolutionize science and medicine. Pediatrics will be one of the first medical specialties to benefit from the outcome of this project as recombinant DNA manipulations will replace diet therapies for treating metabolic diseases. Somatic gene therapy eventually may be the ideal means for diagnosis, treatment, and cure of inherited diseases and metabolic disorders; however, many problems exist, especially in situations in which nutrients are involved in the complex regulation of gene expression. DNA and genes themselves do not determine the fate of an individual. The genetic material provides the potential for the individual, but this potential can be modified by environmental factors. The interaction of nutrients with genes is a major determinant in the final outcome of the individual. Biotechnology promises children a more productive and better quality of life, but achieving the full potential of this promise demands a continued diligent search for knowledge of nutrition and nutrient-gene interactions.

Biotechnology↗

Intraarticular carcinogenesis bioassays of CoCrMo and TiAlV alloys in rats.

Wear-debris powders of cobalt-chromium-molybdenum (CoCrMo) and titanium-aluminum-vanadium (TiAlV) alloys, which are widely used for orthopedic implants (eg, hip and knee prostheses), were tested for carcinogenic activity following intraarticular administration (20 mg/rat) to groups of 44 male Fischer-344 rats (Charles River Breeding Laboratories, North Wilmington, MA). Control groups received similar intraarticular injections of either a noncarcinogen (manganese powder, negative control rats) or a potent carcinogen (nickel subsulfide powder, positive control rats). The experimental groups of 8-12 rats were observed for 24 months after injection. No local tumors developed at the injection site in the negative control rats or in rats that received the CoCrMo or TiAlV powders; poorly differentiated or pleomorphic sarcomas developed at the injection site in 10 of the 12 positive control rats that were treated with nickel subsulfide. Incidences of primary tumors distant from the injection site did not differ significantly among the experimental groups. This study shows that, under experimental conditions, any carcinogenic activity of CoCrMo or TiAlV wear-debris powders is weak in comparison to nickel subsulfide. Based on this study and observations in other laboratories, intraarticular administration of test materials to rats provides a practical, reliable, and biologically relevant method for carcinogenesis testing of biomaterials used for orthopedic implants.

Alloys↗

Prosthetic component failures in hip arthroplasty surgery.

A survey was conducted of the entire membership of the American Association of Hip and Knee Surgeons to determine their experience with total hip arthroplasty (THA) device-related failures. Forty-seven percent of the membership reviewed their preceding 5-year clinical experience and returned the survey instrument. The aggregate 5-year volume encompassed experience with more than 60,000 hip arthroplasties. The median 5-year experience per respondent was 200 metal-based sockets and 214 metal stems. The frequency distribution of the number of hip arthroplasties per respondent was skewed to the right, with fewer surgeons reporting the higher volumes of arthroplasties. In aggregate, 60,115 of the acetabular components used were metal backed. Nonmetal acetabular component usage totaled 3,219. Complete polyethylene failure was defined as fracture or complete wear through of the polyethylene portion of the component. Complete polyethylene failure was seen in 172 metal-backed sockets (29/10,000). Seventy-seven all-polyethylene sockets had complete polyethylene failure (239/10,100). A total of 87 THAs were revised for modular acetabular dissociations for a dissociation rate of 15/10,000. In aggregate, 64,483 metal-stemmed components were used. Femoral stem fractures occurred in 172 for a rate of 27/10,000. A total of 56,965 metallic femoral components were reported as being modular. Dissociation between the femoral head and neck was uncommonly seen (3/10,000). Use of ceramic femoral heads was low (5,023); however, a total of 11 ceramic head fractures were revised in the 5-year period for a failure rate of 22/10,000. The risks of catastrophic prosthetic THA failure are low but vary according to hip component and the manufacturer of the part.

Ceramics↗

Dietary ferric vs. ferrous iron in copper-deficient rats fed fructose-based diets.

OBJECTIVE: This preliminary study was undertaken to determine whether the valence state of dietary iron affects signs associated with copper deficiency in rats fed fructose. METHODS: Rats were fed either copper-deficient or adequate diets containing 62% fructose as the sole dietary carbohydrate for 5 weeks. The mineral mixture contained equal concentration of either ferric or ferrous iron. RESULTS: Copper deficiency resulted in growth retardation, anemia, heart hypertrophy but pancreatic atrophy. The consumption of ferrous iron resulted in increased hematocrit and pancreas size. The combination of ferrous iron with copper deficiency reduced heart size. CONCLUSIONS: Copper deficiency had a major impact on each parameter measured. Although the valence state of iron did not protect the rats against the pathological consequence of copper deficiency it did have some positive effects. It may be that ferrous iron is a more available form than ferric iron.

Anemia↗

Postcaesarean section uterovesical fistula lined by persistent intermediate trophoblast.

We report a unique case of a postcaesarean section uterovesical fistula lined by intermediate trophoblast. The patient, a 42-year-old woman, presented with cyclical haematuria, and she had had a lower segment caesarean section 1 year previously. She was found to have uterovesical fistula, which was excised. On microscopic examination the fistula tract was lined by intermediate trophoblast characterised by cells with abundant eosinophilic cytoplasm, occasional multiclefted nuclei, and cytoplasmic immunoreactivity for epithelial cytokeratins and human placental lactogen. This finding has not, to our knowledge, been previously described and indicates that the survival of third trimester intermediate trophoblast is independent of pregnancy.

Adult↗

Deletion of DNA lying close to the glkA locus induces ectopic sporulation in Streptomyces coelicolor A3(2).

Streptomyces coelicolor A3(2) J1668 sporulated ectopically in the substrate hyphae (the Esp phenotype) with the same time course as sporulation in the aerial hyphae. Examination of related strains implied that the Esp phenotype was caused by the deletion of DNA that lies close to, but is distinct from, the glucose kinase gene (glkA). Co-transduction of the Esp phenotype with the deletion present in J1668 confirmed this hypothesis. The size of the deletion was found to be 7.4 kb. Construction of a strain carrying both the J1668 deletion and a whiG mutation demonstrated that the Esp phenotype depends on at least one of the genes required for the differentiation of aerial hyphae into spores.

Bacterial Proteins↗

The treatment of osteoarthritis of the knee with pulsed electrical stimulation.

OBJECTIVE: The safety and effectiveness of pulsed electrical stimulation was evaluated for the treatment of osteoarthritis (OA) of the knee. METHODS: A multicenter, double blind, randomized, placebo controlled trial that enrolled 78 patients with OA of the knee incorporated 3 primary efficacy variables of patients' pain, patients' function, and physician global evaluation of patients' condition, and 6 secondary variables that included duration of morning stiffness, range of motion, knee tenderness, joint swelling, joint circumference, and walking time. Measurements were recorded at baseline and during the 4 week treatment period. RESULTS: Patients treated with the active devices showed significantly greater improvement than the placebo group for all primary efficacy variables in comparisons of mean change from baseline to the end of treatment (p < 0.05). Improvement of > or = 50% from baseline was demonstrated in at least one primary efficacy variable in 50% of the active device group, in 2 variables in 32%, and in all 3 variables in 24%. In the placebo group improvement of > or = 50% occurred in 36% for one, 6% for 2, and 6% for 3 variables. Mean morning stiffness decreased 20 min in the active device group and increased 2 min in the placebo group (p < 0.05). No statistically significant differences were observed for tenderness, swelling, or walking time. CONCLUSION: The improvements in clinical measures for pain and function found in this study suggest that pulsed electrical stimulation is effective for treating OA of the knee. Studies for longterm effects are warranted.

Adult↗

Glucose repression in Streptomyces coelicolor A3(2): a likely regulatory role for glucose kinase.

The glucose kinase gene (glkA-ORF3) of Streptomyces coelicolor A3(2) plays an essential role in glucose utilisation and in glucose repression of a variety of genes involved in the utilisation of alternative carbon sources. These genes include dagA, which encodes an extracellular agarase that permits agar utilisation. Suppressor mutants of glkA-ORF3 deletion strains capable of utilising glucose (Glc+) arise at a frequency of about 10(-5) on prolonged incubation. The Glc+ phenotype of the mutants is reversible (at a frequency of about 10(-3) and reflects either the activation of a normally silent glucose kinase gene or the modification of an existing sugar kinase. Although the level of glucose kinase activity in the Glc+ supressor mutants is similar to that in the glkA+ parental strain, glucose repression of dagA remains defective. Expression of the glucose kinase gene of Zymomonas mobilis in glkA-ORF3 mutants restored glucose utilisation, but not glucose repression of dagA. Over-expression of glkA-ORF3 on a high-copy-number plasmid failed to restore glucose repression of dagA in glkA-ORF3 mutants and led to loss of glucose repression of dagA in a glkA+ strain. These results suggest that glucose phosphorylation itself is not sufficient for glucose repression and that glkA-ORF3 plays a specific regulatory role in triggering glucose repression in S. coelicolor A3(2).

Blotting, Southern↗

Bone demineralization induced by cementless alumina-coated femoral stems.

The biologic compatibility of ceramic materials has been widely demonstrated, and alumina (Al2O3) has been used extensively in clinical applications for nearly 20 years. The authors examined the behavior of bone tissue adjacent to the alumina coating in eight cementless hip prosthetic stems that appeared radiologically stable and were explanted because of pain. Histologic evaluation demonstrated the presence of a consistent layer of decalcified bone tissue in continuity with and parallel to the prosthetic interface. Based on laboratory findings, the authors attribute this demineralization phenomenon to a high local concentration of aluminum ions with metabolic bone disease, which is histologically comparable to the osteomalacic osteodystrophy described in dialysis patients. These findings must be carefully considered given the potential long-term implications for alumina-coated implants.

Aged↗

Requirements for biotin are not affected by the combination of copper deficiency and fructose feeding.

OBJECTIVE: The objective of the present study was to establish whether copper (Cu)-deficient rats fed a diet containing fructose as their sole carbohydrate source require more biotin than the recommended 2 mg/kg diet when egg-white serves as the dietary protein. METHODS: Eighty weanling male Sprague-Dawley rats were randomly divided into 8 groups according to type of dietary carbohydrate (starch or fructose), level of Cu (0.6 micrograms Cu/g diet or 6.0 micrograms Cu/g diet) and level of biotin (2 mg/kg diet or 10 mg/kg diet). RESULTS: Regardless of the level of dietary biotin, Cu-deficient rats fed a fructose-containing diet exhibited growth retardation, anemia, atrophied pancreata, enlarged hearts and similar death rates. The remaining Cu-deficient rats fed fructose were emaciated and sick regardless of dietary biotin levels. The concentration of biotin in serum and biotin content of liver of rats fed fructose were higher than corresponding values from rats fed starch. CONCLUSION: Cu-deficient rats fed fructose are not deficient in biotin compared to published normal values. Supplementation of 10 mg/biotin/kg diet did not improve morbidity or mortality and therefore was not beneficial.

Animals↗

Copper deficiency in rats: the effect of type of dietary protein.

The present investigation was conducted to determine whether type of dietary protein can exacerbate the pathology induced by the combination of fructose feeding and copper (Cu) deficiency. Weanling male Sprague-Dawley rats were assigned to three different groups differing in the nature of dietary protein. The proteins used were egg-white, casein or lactalbumin. All diets contained 62.5% carbohydrate as fructose and were low in Cu (0.6-0.72 microgram Cu/g diet). Although the lowest concentration of Cu was found in the livers of rats fed egg-white, the pathology associated with Cu deficiency was more severe in rats fed lactalbumin. The highest concentration of hepatic Cu was found in rats fed casein. The data show that the type of dietary protein can exacerbate signs associated with Cu deficiency. The concentrations of hepatic Cu do not reflect accurately the pathology associated with Cu deficiency.

Animals↗

Genetic analysis of the phi C31-specific phage growth limitation (Pgl) system of Streptomyces coelicolor A3(2).

The phage growth limitation (Pgl) system of Streptomyces coelicolor A3(2) was shown to be specific to phi C31 homo-immune phages, and to be absent from the closely related strain Streptomyces lividans. A 16 kb fragment of S. coelicolor A3(2) DNA was isolated which complemented the Pgl- phenotype of J1501, a pgl mutant derivative of the Pglts S. coelicolor strain M130. The cloned DNA complemented only half of the available pgl mutants, which therefore represented at least two groups, designated Pgl class A and class B strains. It follows that more than one kind of high-frequency genetic event can lead to the Pgl- phenotype. Crosses between class A and class B strains yielded high frequencies of Pgl+ recombinants. Crosses between strains of the same class gave no Pgl+ recombinants. The cloned DNA was altered by deletion or apparent point mutation upon passage through the two class B strains tested, such that it was no longer capable of complementing class A strains. This accumulation of mutations might suggest that the expression of the cloned DNA is toxic to at least some class B strains. The nature of the genetic instability associated with the Pgl system was not detectable by Southern blot analysis.

Bacteriophages↗

Low dietary iron prevents free radical formation and heart pathology of copper-deficient rats fed fructose.

Two studies were conducted to determine whether hepatic iron overload in rats fed fructose plays a role in the exacerbation of the signs associated with copper deficiency. When fed the adequate iron diet (50 micrograms Fe/g), copper-deficient rats fed either fructose or starch exhibited hepatic iron overload of similar magnitude. However, only livers of copper-deficient rats fed fructose exhibited the presence of high peaks associated with an iron compound detected by electron spin resonance. In addition, only copper-deficient rats fed fructose developed anemia, pancreatic atrophy, and heart hypertrophy with histopathologic changes, and they died prematurely of heart-related abnormalities. Lowering dietary iron from 50 micrograms/g to 30 micrograms/g was not sufficient to protect the animals against the pathologic consequences of copper deficiency. In contrast, the consumption of a fructose diet inadequate in both copper (0.6 micrograms/g) and iron (17 micrograms/g) resulted in the reduction of hepatic iron, which in turn caused the amelioration of the deficiency, compared with rats fed the adequate iron (50 micrograms/g) diet. None of these rats developed pancreatic atrophy, none exhibited myocardial lesions, and none died of the deficiency. Electron spin resonance spectra of their livers did not show the presence of free radicals. The data suggest that hepatic iron overload plays a role in the exacerbation of copper deficiency only when fructose diets are consumed.

Animals↗

The effect of time of introduction of a high-fructose, low-copper diet on copper deficiency in male rats.

The purpose of the present study was to compare the time of introduction of the high-fructose low-copper diet on the expression of copper (Cu) deficiency. Weanling male rats were randomly assigned to either a diet containing 62.7% fructose or starch, and 6.0 (F+Cu) or 0.6 (S-Cu) microgram Cu/g diet, respectively, for either 1, 2, or 3 wk before being transferred to a diet containing fructose and inadequate in copper (F-Cu). At week 10, body weight and relative heart size of rats initially consuming the F + Cu diet was inversely related to the week placed on the F-Cu diet, but not for those initially consuming S-Cu. Hematocrit, hepatic Cu concentration and RBC superoxide dismutase activity were significantly lower in rats initially consuming S-Cu when compared to those fed F + Cu. Mortality was greatest in rats switched to the F-Cu diet at weeks 1 and 2 when compared to those switched at week 3 regardless of the type of diet initially consumed. Plasma cholesterol, triacylglycerols, and blood urea nitrogen concentrations were not significantly altered by the type of diet initially consumed or by the time of introduction of the F-Cu diet. It was concluded that changing rats to a F-Cu diet at 1, 2, or 3 wk after weaning did not significantly improve some of the characteristic signs associated with Cu deficiency, but the later that the F-Cu diet was introduced after weaning the greater the chances for survival.

Aging↗

The influence of dietary carbohydrate and deferoxamine on developing copper deficiency of rats.

The present investigation was conducted to follow the development of copper deficiency in male rats from weaning (day 0) to day 31 of dietary copper deprivation and to correlate changes in tissue sizes with copper and iron concentrations. Male rats were fed for 31 days from weaning copper-deficient or adequate diets containing fructose or starch. Another copper-deficient group of rats that was fed fructose was treated with deferoxamine. Rats were killed at day 0, 8, 16, 24, and 31 of the study. In general, no correlation could be found between the development of heart hypertrophy, pancreatic and thymic atrophy, and tissue copper concentrations in copper-deficient rats fed fructose. In contrast, in the heart and pancreas a negative correlation existed between tissue size and iron concentration. In addition, anemia preceded heart hypertrophy. Deferoxamine lowered hepatic iron concentrations, ameliorated the anemia, and decreased heart size compared with untreated rats. The data of the present study suggest that tissue atrophy and hypertrophy and the severity of copper deficiency are not solely due to tissue concentrations of iron and/or copper.

Animals↗

The influence of gender on developing copper deficiency and on free radical generation of rats fed a fructose diet.

The present investigation was conducted to determine whether differences in copper and iron status between male and female rats can be detected during the development of copper deficiency. These differences may explain the protection of the female against the severity of copper deficiency. In addition, the livers of all rats were exposed to electron-spin resonance (ESR) spectroscopy for the presence of free radicals. Male and female rats were fed from weaning either copper-deficient or -adequate diets containing fructose for 31 days. Rats were killed at day 0, 8, 16, 24, and 31 of the study. Throughout the study, copper-deficient males exhibited the same organ copper concentrations as copper-deficient female rats. However, only in the male did copper deficiency cause a reduction in body weight and an increase in liver and heart sizes but a decrease in pancreas size. In contrast, organ iron concentrations were different between males and females. Only copper-deficient males were anemic. Only the livers of copper-deficient males showed the presence of free radicals. Although the livers of copper-deficient female rats exhibited higher concentrations of hepatic iron than their male counterparts, their livers did not show the presence of free radicals. The data of the present study suggest that changes in organ sizes and the severity of copper deficiency are not solely due to the total concentrations of iron and/or copper. The type of iron compound and the presence of free radicals may be involved in the pathology of copper deficiency of the male.

Analysis of Variance↗