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Biomedical subjects

N J Lewis

Publications and source records attributed to N J Lewis.

At least 37 records · Page 2Linked to original sources
PubMed1991

Body surface area, a reference for space allowance in confinement.

One of the most important welfare concerns in relationship to poultry production is the restriction, both physical and social, imposed by close and long-lasting confinement. The bird's body-surface area was considered as a reference base for the determination of a minimum space allowance in the present study. The formula for surface area was based on body weight, which is a well-known and easily measured parameter. As the bird grows, its surface area changes in proportion to its weight gain, and, therefore, surface area provides a continuous estimate of the space requirement. The floor space allowance can be easily visualized from body surface area and estimated without extensive measurements of birds and floor areas. It is recommended that the minimum space requirement for poultry should be no less than the equivalent of 50% of the bird's body surface area. This recommendation was based on the principle that all birds in an enclosure should be able to rest simultaneously without contacting another bird or the walls of the enclosure.

Animals↗
PubMed1990

Occupational health and hygiene following a fire in a warehouse with an asbestos cement roof.

This paper deals with the occupational health and hygiene advice that was given in the immediate aftermath and clean-up period of a major fire in a large warehouse with an asbestos cement roof. Work on site was carefully monitored and we believe that no health hazards occurred subsequent to the fire, in particular only very low levels of asbestos were detected during the clean-up. In addition, the need to disseminate information as widely and as rapidly as possible to the workforce and others following such a disaster is emphasized.

Asbestos↗
PubMed1990

Locomotion of broiler chickens in floor pens.

Locomotion has a major effect on production and animal welfare as it relates to feed and water acquisition, feed utilization, carcass quality, health, and physical vigor. The locomotor abilities of the broiler are also important considerations in pen design and placement of feed and water dispensers. To study the locomotion of broiler chickens and the effect stocking density has on locomotion, eight groups of broiler chickens were observed in an experimental floor pen (1.2 by 1.7 m). A Videomex V Image Motion Computer was used to determine the distance traveled and the frame-by-frame (30 frames per s) location of a focal bird. Four densities (660, 790, 990, and 1320 cm2 per bird) were tested, one on each day of the 4-day recording period for each group of birds. Broiler chickens were active throughout the day and traveled an average distance of 8.8 m per h or 212 m per day. Increasing housing density reduced the distance traveled (10, 8.8, 8.5, and 8.1 m per h for 1,320, 990, 790, and 660 cm2 per bird, respectively) but did not affect the average number of visits to the feeders (4 per h) and water cups (2 per h). The focal birds used the total space provided during the day, indicating that they were not consistently socially restricted to certain areas of the pen.

Animals↗
PubMed1987

Effects of farrowing crate floors on health and performance of piglets and sows.

Three types of raised perforated floor were compared with floor-level concrete which had perforated flooring at the rear. Piglets on raised perforated floors grew faster (P less than 0.05) to 21 days than pigs on mainly solid floors (205 g/day and 198 g/day, respectively). The mortality in the first 21 days of all pigs born did not differ between raised (18.4 per cent) and mainly solid floors (18.7 per cent) and there were no effects of individual floor types on overall survival or on deaths due to crushing. The incidence of diarrhoea was not significantly less on raised than on solid floors (27 per cent and 34 per cent of litters, respectively) but antibiotic treatment time was shortened (0.9 days and 1.2 days, P less than 0.05). The incidence of splayleg was highest on fibreglass slats. Concrete floors caused most knee abrasions but the incidence of arthritis was unaffected. Approximately twice as many sows on mainly solid floors went off their feed or had a high rectal temperature compared with sows on raised perforated floors. No differences were observed between narrow or A-frame farrowing crates.

Animals↗
PubMed1986

The 1986 McCollum award lecture. Fuel-mediated teratogenesis during early organogenesis: the effects of increased concentrations of glucose, ketones, or somatomedin inhibitor during rat embryo culture.

Whole rat embryos were explanted at head-fold, late pre-somite stage (day 9.5 of gestation) and cultured in rat sera varyingly supplemented with glucose (3, 6, 9, or 12 mg/mL), D,L sodium beta-hydroxybutyrate (2, 4, 8, or 16 mM), or both (6 mg/mL D-glucose plus 8 mM beta-hydroxybutyrate). During 48 h culture, increasing glucose alone or beta-hydroxybutyrate alone effected growth retardation and faulty neural and extraneural organogenesis in dose-dependent fashion. Synergistic dysmorphogenic effects occurred when minimally teratogenic concentrations of glucose and beta-hydroxybutyrate were combined. Sera from diabetic animals containing somatomedin inhibitor bioactivity were also able to produce growth retardation and major developmental lesions in presence of amounts of glucose and ketones which of themselves were not teratogenic. Thus, aberrant fuels and fuel-related products can impair growth and organogenesis in early post-implantation embryo. Such fuel-mediated teratogenesis may be multifactorial and include possibilities for synergistic and additive interactions.

3-Hydroxybutyric Acid↗
PubMed1985

Fuel-mediated teratogenesis. Use of D-mannose to modify organogenesis in the rat embryo in vivo.

The unique embryotoxic properties of D-mannose have been used as the basis for a new technique to secure precise temporal correlations between metabolic perturbations during organogenesis and subsequent dysmorphogenesis. Conscious, pregnant rats were infused with D-mannose or equimolar amounts of D-glucose by "square wave" delivery during the interval in which the neural plate is established and early fusion of neural folds takes place, that is, days 9.5-10.0 of gestation. Infusions of mannose to maternal plasma levels of 150-200 mg/dl did not elicit any toxicity in the mothers: motor activity, eating behavior, and serum components (electrolytes, osmolality, bilirubin) did not differ in glucose- vis-à-vis mannose-infused dams. Embryos were excised by hysterotomy on day 11.6 for evaluation of development. Examination with a dissecting microscope did not disclose developmental abnormalities in any of the 136 embryos from glucose-infused mothers or in 62 additional embryos from mothers that had not received any infusions. By contrast, dysmorphic changes were seen in 17 of 191 embryos (8.9%) from mannose-infused mothers. 14 of the 17 had abnormal brain or neural tube development with incomplete neural tube closure in 9 instances. Abnormal axial rotation was present in 8 of the 191 embryos (4.2%) and lesions of the heart or optic vesicles were seen in 4 (2.1%) and 3 (1.6%), respectively. Embryos from mannose-infused mothers displayed significant retardations in somite number, crown-rump length, and total protein and DNA content. These stigmata of growth retardation were more marked in the 17 dysmorphic embryos. The experiments indicate that D-mannose may be employed in model systems with rodents for precisely timed interruptions of organogenesis in vivo. Initial applications are consistent with our earlier suggestion that multiple dysmorphic changes may supervene after interference with communally observed metabolic dependencies during organogenesis. The studies do not identify the vulnerable site(s) within the conceptus (e.g., investing membranes, embryos, or both). However, the findings suggest that dysmorphic events are manifest most markedly in a general setting of embryo growth retardation.

Abnormalities, Drug-Induced↗
PubMed1984

The honeybee syndrome - implications of the teratogenicity of mannose in rat-embryo culture.

Lethal effects of D-mannose in the honeybee have been recognized for more than a half a century. We observed another toxic effect of D- mannose during culture of rat embryos from the early head-fold stage to the 26-to-29-somite stage (Days 9-1/2 through 11-1 of gestation). The addition to culture mediums of 1.5 mg of D-mannose per milliliter caused growth retardation and faulty neural-tube closure in approximately two thirds of the embryos. Mannose effects occurred during the first 24 hours of culture and were attended by modes inhibition of the glycolysis that constitutes the principal energy pathway at this stage of development. Adding more glucose to preserve glycolytic flux or increasing atmospheric oxygen to promote oxidative metabolism offset the mannose teratogenesis. Our findings highlight the metabolic vulnerabilities that exist during early organogenesis, before oxidative flexibility is established. They may serve as a model to explain the teratogenicity of many other seemingly unrelated agents that could act by perturbing glycolysis at this vulnerable stage.

Abnormalities, Drug-Induced↗
PubMed1984

Synergistic effect of N-acetyl-D-glucosamine (NAG) on mitogenic, antigenic and allogeneic stimulation of normal human lymphocytes.

The effect of N-acetyl-D-glucosamine (NAG) on in vitro stimulated human peripheral blood lymphocytes was investigated. NAG was added to lymphocyte cultures stimulated by the mitogen PHA, the antigen PPD or to one-way-stimulated mixed lymphocyte cultures from unrelated donors. The results indicate that NAG (1-2 micrograms/ml) in appropriate experimental conditions has an enhancing effect on DNA and protein synthesis induced by PHA, PPD and allogeneic cells. Addition of NAG (1-2 micrograms/ml) to unstimulated lymphocyte cultures had no effect on DNA or protein synthesis.

Acetylglucosamine↗
PubMed1984

Differential effects of age versus glycemic stimulation on the maturation of insulin stimulus-secretion coupling during culture of fetal rat islets.

We have cultured islets from 21.5-day-old fetal rats for 1-7 days in RMPI 1640/10% fetal calf serum containing 2.8 or 11.1 mM glucose to evaluate the differential effects of age vis-à-vis glycemic stimulation on the maturation of selected components of stimulus-secretion coupling. After 1 day of culture in either media, acute stimulation with 3.0 mg/ml glucose during basal perifusion with 0.5 mg/ml glucose elicited only a small first phase of stimulated insulin secretion and no second phase. The acute exposure to 3.0 mg/ml glucose produced no change in the prevailing high rates of oxygen consumption (QO2) and caused only minor increments in phosphate efflux (i.e., peak values for phosphate flush of 126 +/- 16% of baseline for islets that had been cultured in 11.1 mM glucose and 162 +/- 30% for islets cultured in 2.8 mM glucose). After 7 days of culture in 11.1 mM glucose, acute stimulation with 3.0 mg/ml glucose increased Qo2 (as in adult islets) and effected acute increases in the AT32P and GT32P content of prelabeled islets. The 3.0 mg/ml glucose also triggered phosphate flush to 599 +/- 45% of baseline and elicited first as well as early second phases of stimulated insulin secretion that replicated the performance of adult islets. By contrast, after 7 days of culture in 2.8 mM glucose, similar acute exposures of fetal islets to 3.0 mg/ml glucose effected only a small first phase and a negligible second phase of stimulated insulin secretion despite the occurrence of the same increments in Qo2 as after culture in 11.1 mM glucose, highly significant increases in AT32P and GT32P, and phosphate flushes that peaked at 306 +/- 16% of basal values. Thus, the ontogeny of individual components of stimulus-secretion coupling may occur in asynchronous fashion and varying require glycemic stimulation in addition to aging per se. The capacities to augment efflux of orthophosphate, enhance respiration, and heighten nucleotide turnover in response to acute stimulation with glucose seem to mature in large measure in time-dependent fashion, whereas some chronic exposure to ambient glucose in excess of basal levels may be required to establish and/or maintain the other coupled components that underlie biphasic stimulated insulin release. However, we did not achieve full exocytotic maturation even after 7 days of culture with 11.1 mM glucose.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗
PubMed1984

Growth retardation during early organogenesis in embryos of experimentally diabetic rats.

Embryos from rats rendered diabetic with streptozotocin for 1 wk or more before conception were examined on day 11.5 of gestation (i.e., at the 26-29-somite stage of normal rat embryonic development). The studies were designed to assess whether poorly regulated maternal diabetes is associated with demonstrable abnormalities even during this early phase of embryogenesis. We found that manifest retardations in growth and development were invariably present as judged by significant reductions in crown-rump length and somite number, respectively. Total protein and DNA content of the embryos were also reduced, although not symmetrically, so that protein/DNA ratios were increased. Gross dysmorphogenic lesions in neural tissue disproportional to the overall growth retardation at 11.5 days could not be demonstrated. The findings suggest that maternal diabetes can compromise intra-uterine growth and development during the period preceding and coinciding with the establishment of circulation in the allantoic placenta. The possible multifactorial determinants remain to be elucidated. It also remains to be established whether the early embryotoxicity provides a setting conducive to the increased dysmorphogenesis that is traditionally recognized during the later stages of pregnancy complicated by diabetes.

Animals↗
PubMed1983

The honeybee syndrome: teratogenic effects of mannose during organogenesis in rat embryo culture.

The relevance of our present findings should not rest on the possible role of mannose as an important teratogen in man. Excessive exposure to mannose during pregnancy via dietary intake seems unlikely since mannose is absorbed poorly from the gastrointestinal tract and intestinal hydrolysis of mannosidic linkages may be minimal. Moreover, although some plasma mannose may be generated continuously from endogenous sources via the cleavage of mannose-6-phosphate by hepatic glucose-6-phosphatase or mannosidic linkages by other hydrolases, our ongoing surveys have not uncovered any specimens of plasma or amniotic fluid containing mannose in amounts which could compete effectively with prevailing levels of glucose. Although we are continuing to monitor clinical samples for unusual mannose levels, we believe that the major significance of our experiences with this hexose pertains to its applications as a physiological tool for evaluating the metabolic determinants of early organogenesis. Within the above context, our findings must be viewed in relation to the known features of energy metabolism in the embryo during the interval that we have studied (Fig. 9). The classic studies of Shepherd and colleagues, similar findings by others, and more recent experiments in our own laboratory have indicated that glycolysis constitutes the chief energy source for the post-implantation embryo prior to the establishment of the yolk sac circulation on day 10 1/2. Almost all of the assimilated glucose goes to lactic acid, mitochondrial electron transfer is poorly developed, and oxidative metabolism via the Krebs' cycle is minimal. Meaningful Krebs' cycle activity does not become operative until day 10 1/2 and full expression is not found until the establishment of the allantoic circulation on day 11 (Fig. 9). The present experiences with mannose provide the first documentation of how precariously development is balanced during that transitory 9 1/2-10 1/2 day phase of organogenesis when glycolysis predominates. We have shown that even minor perturbations of glycolytic flux during that interval can result in major dysmorphogenic sequelae. Thus, the proposition by Kalter and Warkany that "any meaningful attempt to reduce infant mortality further will have to address the still unresolved causes of congenital malformations" prompts our speculation that major congenital lesions may result from relatively minor disturbances in glycolysis occurring prior to oxidative maturation in the embryo unit. Such effects on glycolysis during this vulnerable phase of embryogenesis could provide a common basis for the teratogenic actions of many unrelated and as yet unidentified agents.(ABSTRACT TRUNCATED AT 400 WORDS)

Abnormalities, Drug-Induced↗
PubMed1980

Inhibition of S37 ascites cell amino acid transport systems by alpha-chloromethylketone analogs.

Alanine chloromethylketone and leucine chloromethylketone were synthesized and their effects on amino acid transport in sarcoma 37 mirone ascites tumor (S37) cells were studied. Alanine chloromethylketone preincubation weakly inhibited system A. Leucine chloromethylketone preincubation strongly inhibited both amino acid transport systems L and A. Leucine chloromethylketone was also a competitive inhibitor of leucine transport. Labeled leucine chloromethylketone was concentrated by S37 cells. Leucine chloromethylketone preincubation inhibition was concentration dependent and partial protection of transport was afforded by leucine. Steady-state retention of amino acids was decreased more than the initial velocity of transport by leucine chloromethylketone preincubation. Glutathione was also depleted. Labeled leucine chloromethylketone was incorporated in a plasma membrane protein fraction comigrating on a DEAE-cellulose column (DE52) with gamma-glutamyltranspeptidase activity. There was a modest increase in vital staining after treatment of S37 cells with leucine chloromethylketone, and glucose uptake was also inhibited. Whilst several effects occur during treatment of S37 cells with leucine chloromethylketone, it is suggested than one prominent effect is alkylation of amino acid transport system components.

Alanine↗
PubMed1980

Morphologic study of cultured pancreatic fetal islets during maturation of the insulin stimulus-secretion mechanism.

We recently described a tissue culture system in which 21.5-day-old fetal rat islets underwent an in vitro maturation of insulin stimulus-secretion coupling over a period of 7 days. During the same period, the acinar part of the explanted fragments degenerated and the islets became isolated, seeming to increase in mass. In the present study, we have utilized these characteristic morphologic changes in an attempt to evaluate the extent that apparent islet growth reflects multiplication of preformed beta cells or the neogenesis of these cells from ductular or acinar cells. In the first days of culture, continuity between islets and ducts could be demonstrated, and the islets appeared to "bud" from the ducts. During this time, only insulin- and glucagon-positive cells could be demonstrated immunocytochemically, and the 3H-thymidine incorporation index of the beta cells (expressed as the percentage of beta cells labeled during 24 h or exposure to 3H-thymidine and 3 h of "chase") in the "budding" islets was 28.7 +/- 2.6. After 7 days in culture, i.e., after maturation of the insulin stimulus-secretion mechanism, the islets were no longer associated with ductular epithelium. At this stage, insulin-, glucagon-, and occasional somatostatin-positive islet cells could be demonstrated, and the 3H-thymidine incorporation index of the beta cells was significantly decreased to 16.7 +/- 2.8. These observations are taken to support previous suggestions of a possible neogenesis of beta cells from duct epithelium in the rat. This tissue culture technique appears well suited for further detailed studies of this neogenesis.

Animals↗
PubMed1979

Diels-Alder adducts of fulvenes and halogenated dienes. Synthesis and insecticidal activity.

A series of eight adducts (1--8) of substituted fulvenes and polychlorinated cyclodienes was synthesized by Diels-Alder cyclization. The products isolated were the endo bicyclo adducts as determined by detailed 1H and 13C NMR spectral analysis. Steric hindrance of end-product bridge substituents coupled with bulky substituents at C6 of the fulvenes led to one isomeric product in most cases. Compounds 1--8 demonstrated weak insecticidal action in Musca domestica as determined by topical LD50 and oral LC50 assays.

Animals↗
PubMed1978

The genetic control of the molybdoflavoproteins in Aspergillus nidulans. IV. A comparison between purine hydroxylase I and II.

The purine hydroxylases I and II of Aspergillus nidulans [previously called xanthine dehydrogenases I and II: Scazzocchio, Holl and Foguelman, Eur. J. Biochem. 36, 428--445 (1973)] have been studied in crude extracts. The two enzymes differ in their substrate specificities, purine hydroxylase II being able to accept nicotinate as a substrate and unable to hydroxylate xanthine. The kinetics of inhibition with allopurinol and oxypurinol are also different, the two analogues being pseudo-irreversible inhibitors of purine hydroxylase I, while allopurinol is a competitive inhibitor of purine hydroxylase II and oxypurinol shows anti-competitive inhibition. Differences in electro-phoretic mobility and molecular size are also shown. We have failed to show the formation of hybrid purine hydroxylase I/II molecules. While a common evolutionary origin of the purine hydroxylases could be postulated, the data reveal a considerable divergence.

Aspergillus nidulans↗