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Biomedical subjects

J Lincoln

Publications and source records attributed to J Lincoln.

At least 19 recordsLinked to original sources

Engineering and public health at CDC.

Engineering is the application of scientific and technical knowledge to solve human problems. Using imagination, judgment, and reasoning to apply science, technology, mathematics, and practical experience, engineers develop the design, production, and operation of useful objects or processes. During the 1940s, engineers dominated the ranks of CDC scientists. In fact, the first CDC director, Assistant Surgeon General Mark Hollis, was an engineer. CDC engineers were involved in malaria control through the elimination of standing water. Eventually the CDC mission expanded to include prevention and control of dengue, typhus, and other communicable diseases. The development of chlorination, water filtration, and sewage treatment were crucial to preventing waterborne illness. Beginning in the 1950s, CDC engineers began their work to improve public health while developing the fields of environmental health, industrial hygiene, and control of air pollution. Engineering disciplines represented at CDC today include biomedical, civil, chemical, electrical, industrial, mechanical, mining, and safety engineering. Most CDC engineers are located in the National Institute for Occupational Safety and Health (NIOSH) and the Agency for Toxic Substances and Disease Registry (ATSDR). Engineering research at CDC has a broad stakeholder base. With the cooperation of industry, labor, trade associations, and other stakeholders and partners, current work includes studies of air contaminants, mining, safety, physical agents, ergonomics, and environmental hazards. Engineering solutions remain a cornerstone of the traditional "hierarchy of controls" approach to reducing public health hazards.

Centers for Disease Control and Prevention, U.S.↗

Characterisation of Wnt gene expression during the differentiation of murine embryonic stem cells in vitro: role of Wnt3 in enhancing haematopoietic differentiation.

The first haematopoietic stem cells in mammalian and non-mammalian vertebrates are derived from mesoderm, therefore genes that are important in mesoderm patterning and formation might also play an essential role in haematopoietic stem cell commitment and differentiation. Several members of the Wnt gene family are expressed in very specific patterns in embryonic mesoderm and have previously been shown to act as haematopoietic growth factors. In order to investigate in detail the role that such secreted proteins play in the biology of early haematopoietic commitment we have used in vitro differentiation of murine embryonal stem (ES) as a model system. Using reverse-transcriptase polymerase chain reaction analysis we identified several candidate Wnt genes whose expression pattern was consistent with a role in generation, maintenance and/or differentiation of early haematopoietic progenitor cells including three genes previously shown to have a role in haematopoiesis (Wnt5a, Wnt2b and Wnt10b). The most interesting candidate was Wnt3, because of its strong and regulated expression during in vitro differentiation of murine ES cells as well as its early embryonic expression in mesoderm. Overexpression of Wnt3 was sufficient to cause a consistent increase in the number of embryoid bodies committing to haematopoiesis further strengthening the evidence that this protein can enhance haematopoietic commitment during in vitro differentiation of ES cells. In addition, overexpression of Wnt3 caused a marked upregulation of Brachyury expression, thus providing some evidence that Brachyury may be one of the target genes for the Wnt3 signalling pathway.

Animals↗

Improving safety in the Alaskan commercial fishing industry.

OBJECTIVES: Over 90% of deaths in Alaska's commercial fishing industry were due to drowning, following vessel sinkings. In the early 1990's, the U.S. Commercial Fishing Industry Vessel Safety Act required the implementation of safety measures for all fishing vessels. The purpose of our study was to examine the effectiveness of these measures in reducing the high fatality rate of Alaska's commercial fishermen. STUDY DESIGN: Alaska Occupational Injury Surveillance System and AlaskaTrauma Registry data were used to examine fishing fatalities and injuries. Demographic, risk factor, and incident data were analyzed for trend. RESULTS: During 1991-1998, there was a significant (p<0.001) (decrease in Alaskan commercial fishing deaths. Significant progress has been made in saving lives of fishermen involved in vessel sinkings. During 1991-1997, 536 fishermen suffered severe injuries (437/100,000/year). These injuries resulted from being entangled, struck or crushed by equipment (60%) and from falls (25%). CONCLUSIONS: Vessel sinkings still continue to occur, placing fishermen at substantial risk. Efforts toward improving vessel stability and hull integrity and avoidance of harsh weather conditions must be made to further reduce the fatality rate. The nature of non-fatal injuries reflect that modern fishing vessels are complex industrial environments posing multiple hazards. Measures are needed to prevent falls and improve equipment handling and machinery guarding.

Alaska↗

The endothelium and cytokine secretion: the role of peroxidases as immunoregulators.

The endothelium is frequently exposed to many proinflammatory mediators. The present study was done to determine the effects of human recombinant myeloperoxidase (MPO) and porcine eosinophil peroxidase (EPO) on certain endothelial cell (HUVEC) functions. The following areas were evaluated: (1) production of reactive oxygen intermediates (ROI), (2) cytokine secretion, and (3) regulation of mRNA cytokine transcripts. Both MPO and EPO induced the production of ROI, but an enzymatically inactive form of MPO (iMPO) was the most effective. Enzymatically inactive MPO, but not MPO, induced the secretion of interleukins 6 and 8 and granulocyte-monocyte colony-stimulating factor. A ribonuclease protection assay indicated that both iMPO and MPO upregulated mRNA cytokine transcripts; however, the former was markedly more effective. The simultaneous addition of EPO and iMPO resulted in a decrease in cytokine-specific mRNA. These data indicate a major role for peroxidases in the regulation of inflammation.

Animals↗

mTert expression correlates with telomerase activity during the differentiation of murine embryonic stem cells.

Telomerase, the enzyme which maintains the ends of linear chromosomes in eukaryotic cells, is found at low levels in somatic stem cells but while this is incapable of preventing the progressive erosion of telomeres occurring as a consequence of cell division, such cells show greater proliferative capacity than normal somatic cells hence examination of telomerase activity in such stem cells is of interest. Our aim in this work was to examine the relationship between expression of the reverse transcriptase component (mTert) of murine telomerase. We report here the insertion of a reporter cassette comprising a segment of the promoter sequence of murine Tert gene coupled to the coding sequence of green fluorescent protein (GFP) into murine embryonic stem (ES) cells and show that this is sufficient for mimicking the expression of mTert. We show that the expression of mTert is very closely linked to telomerase activity and that both are substantially reduced upon differentiation of ES cells into more committed lineages giving us a potential reporter system for the selection and isolation of ES cells possessing different levels of telomerase activity.

Animals↗

Mitogenic activity of steroidogenesis-inducing protein (SIP) during hypoxic stress of human ovarian carcinoma cells.

Steroidogenesis-inducing protein (SIP) is a novel growth factor isolated from human ovarian follicular fluid. While the steroidogenic and mitogenic effects appear to be restricted towards gonadal cell types, we have recently demonstrated that SIP is also a potent mitogen for cell lines derived from ovarian surface epithelial carcinomas. Here, we demonstrate that SIP reverses hypoxia-induced cell proliferation arrest of the human ovarian carcinoma cell line SKA, as determined by flow cytometry and cell proliferation assays. Concomitant with this reversal of proliferation arrest is an increase in expression of cyclins D and E and a reduction in expression of the cyclin-dependent kinase inhibitor p27. Pretreatment of hypoxic SKA cells with SIP is also shown to increase Taxol sensitivity of these cells by two-fold. These studies further characterize the mitogenic activity of SIP at the molecular level and suggest that this protein may be an effective biological response modifier for ovarian carcinoma cells.

Carcinoma↗

Postnatal development of nitric oxide synthase activity in fast and slow muscles of the rat.

Nitric oxide synthase (NOS) activity was measured in extensor digitorum longus (EDL) and soleus muscles during postnatal development in the rat. At 1 and 2 weeks of age, similar low levels were found in both muscles. After 2 weeks, activity increased significantly only in EDL. Adult NOS activity was significantly higher in EDL than soleus. Thus, the preferential expression of NOS in fast muscle only occurs once the adult pattern of motor activity is established.

Aging↗

Prevalence of inadvertent hypothermia during the perioperative period: a quality assurance and performance improvement study.

The inadvertent hypothermia that is often seen after anesthesia in a cool environment has been associated with delays in recovery from anesthesia and longer stays in the PACU. This quality assurance/performance improvement study was undertaken to determine the following: (1) the effectiveness of current interventions for preventing intraoperative hypothermia, (2) whether there were any apparent differences in effectiveness among the current methods for preventing intraoperative hypothermia, and (3) was intraoperative hypothermia associated with delays in discharge from the PACU. Data were completed on 502 patients. Despite longer surgical procedures, those patients treated intraoperatively with the Bair Hugger (Augustine Medical Inc, Eden Prairie, MN) were less likely to arrive in the PACU hypothermic than those who did not receive this treatment. Patients who arrived in the PACU hypothermic had longer PACU stays than patients who arrived normothermic. As a result of these findings, changes in nursing practice in the PACU and in the availability of the Bair Hugger in the operating rooms were made.

Adolescent↗

Serotonin promotes the differentiation of glutamate neurons in organotypic slice cultures of the developing cerebral cortex.

The monoamines serotonin (5-HT), noradrenaline (NA), and dopamine (DA), which are present in the developing brain apparently before they assume their neurotransmitter functions, are regarded as strong candidates for a role in the maturation of the cerebral cortex. Here we sought to investigate their effects on the generation and differentiation of cortical cell types. Slice cultures, prepared from the cortices of embryonic day (E) 14, E16, and E19 rat fetuses, were kept in defined medium or in defined medium plus 5-HT for 7 d. E16 cortices were also exposed to NA or DA for the same period. At the end of this period, the proportions of the neuronal [glutamate (Glu)-, GABA-, calbindin-, calretinin-labeled], glial (GFAP), and neuroepithelial (nestin) cell types were estimated for all conditions. We found that in E16 cultures, application of 5-HT, but not of NA or DA, significantly increased the proportion of Glu-containing neurons without affecting the overall neuronal population or the proportions of any other cell types. A similar effect was observed in co-cultures of E16 cortex with slices through the midbrain raphe nuclei of E19 rats. The total amount of cortical Glu, as measured with HPLC, was also increased in these co-cultures. To investigate whether the effect of 5-HT was the result of changes in cell proliferation, we exposed slices to bromodeoxyuridine (BrdU) and found that the proportion of BrdU-labeled cells was similar in the 5-HT-treated and control slices. These results indicate that 5-HT promotes the differentiation of cortical Glu-containing neurons without affecting neuroepithelial cell proliferation.

Animals↗

Increase in nitric oxide synthase and NADPH-diaphorase in the adrenal gland of streptozotocin-diabetic Wistar rats and its prevention by ganglioside.

Levels of nitric oxide synthase (NOS) and NADPH-diaphorase in adrenal glands of streptozotocin-diabetic rats of 8 and 12 weeks' duration compared with control rats were assessed with histo-chemical and biochemical techniques. Adrenal glands from streptozotocin-diabetic rats of 8 weeks' duration treated with ganglioside were examined also. In the adrenal medulla of 8-weeks- and 12-weeks-diabetic rats, NOS-immunoreactive nerve fibres were increased and decreased, respectively; additional NOS-immunoreactive and NADPH-diaphorase stained cells, which appeared to be cortical cells, were located in medulla and cortex compared with controls. Increased intensity in NADPH-diaphorase staining of the cortical cells of diabetic rats was observed also. Ganglioside treatment of the 8-weeks-diabetic rats prevented the diabetic-induced increase in NOS-immunoreactive nerve fibres. Also, it reduced most of the increase in the NOS-immunoreactive and NADPH-diaphorase stained cells and the intensity of NADPH-diaphorase staining of cortical cells. With biochemical assay, a significant increase in NOS activity was found in the adrenal glands from 8-weeks-diabetic rats, and this increase was reduced by ganglioside treatment in four out of six diabetic rats. In summary, streptozotocin-induced diabetes causes an initial increase in the levels of NOS and NADPH-diaphorase in the adrenal gland of rat, which was prevented by ganglioside treatment.

Adrenal Cortex↗

Effects of vitamin E deficiency on autonomic neuroeffector mechanisms in the rat caecum, vas deferens and urinary bladder.

1. Modified sucrose-gap, standard organ-bath techniques and transmitter release studies were used to examine neuromuscular transmission in the caecum, vas deferens and urinary bladder in normal rats and in rats maintained for 12 months on a diet free of vitamin E. 2. In the caecum circular muscle, non-adrenergic, non-cholinergic inhibitory junction potentials were absent from 48 and 15% of preparations from vitamin E-deficient and control animals, respectively. Cholinergic excitatory junction potentials were absent from 83 and 8% of vitamin E-deficient and control preparations, respectively. Responses to applied noradrenaline (0.1-30 microM), alpha,beta-methylene ATP (3-100 microM) and acetylcholine (0.1-30 microM) were attenuated or absent in vitamin E-deficient tissues. Responses to applied KCl were similar in both groups. Release of [3H]noradrenaline or endogenous acetylcholine could not be evoked from vitamin E-deficient tissues. 3. In contrast, in isolated preparations of the vas deferens and urinary bladder, neuromuscular transmission by adrenergic, cholinergic and purinergic components were unaffected by long-term vitamin E deficiency. 4. In conclusion, vitamin E deficiency causes dysfunction of autonomic neuroeffector mechanisms in the smooth muscle of the rat caecum, at both a pre- and postjunctional level. The lesions in autonomic transmission mechanisms brought about by long-term vitamin E deficiency were found only in the caecum; no changes in sympathetic neuromuscular transmission were observed in the vas deferens, or in parasympathetic neuromuscular transmission in the urinary bladder.

Adenosine Triphosphate↗

Innervation of cerebral arteries by nerves containing 5-hydroxytryptamine and noradrenaline.

Noradrenaline (NA)-containing nerves, mainly originating in the sympathetic superior cervical ganglia, supply large and small cerebral arteries. In large cerebral arteries, nerves containing serotonin (5-hydroxytryptamine, 5-HT) may represent neuronal uptake of circulating 5-HT by sympathetic nerves. 5-HT-containing nerves supplying small pial vessels probably have a central origin in the dorsal raphe nucleus. In most species, NA is a weak vasoconstrictor (alpha 1- or alpha 2-adrenoceptors), while 5-HT is a potent vasoconstrictor (5-HT2 or 5-HT1-like receptors) of large cerebral arteries. In contrast, both NA and 5-HT tend to cause vasodilatation in small pial vessels and arterioles. Adrenergic and serotonergic transmission can be modulated by pH, a range of putative neurotransmitters and neuromodulators, and by the endothelium. Sumatriptan, a 5-HT1-like receptor agonist, has been shown to be effective in the treatment of migraine. Changes in NA- or 5-HT-containing nerves and/or in the responses of cerebral vessels to NA and 5-HT have been observed in a variety of vascular disorders, including cerebral vasospasm following subarachnoid haemorrhage, hypertension, and atherosclerosis.

Animals↗

Conditions required for the measurement of nitric oxide synthase activity in a myenteric plexus/smooth muscle preparation from the rat ileum.

Nitric oxide synthase (NOS) activity was measured, by the conversion of arginine to citrulline, in a preparation from the rat ileum consisting of the myenteric plexus and smooth muscle layers. A variety of incubating media were used in order to establish the optimal conditions required for the assay. NOS activity was present in the soluble fraction and was Ca(2+)- and calmodulin-dependent, characteristic of neuronal NOS. Exogenous Ca2+ was required for activity to be detectable but NOS activity progressively decreased with Ca2+ concentrations above 1.25 mM. Activity varied with arginine concentration, reaching saturation at 6 microM, and required the addition of the co-substrate NADPH. Endogenous levels of co-factors in the crude soluble fraction were not sufficient to maintain NOS activity. Omission of flavin adenine dinucleotide and tetrahydrobiopterin from the incubation medium reduced activity by 90%, and both co-factors had to be present for maximal activity to occur. These results emphasize the need to control assay conditions when measuring NOS activity in crude preparations from peripheral tissue.

Animals↗

Plasticity in the myenteric plexus of the rat ileum after long-term sympathectomy.

To investigate the effect of chronic sympathectomy on the innervation of a tissue with an extensive intrinsic component, 1-week-old rat pups were treated with 50 mg/kg guanethidine for 3 weeks, a treatment shown to produce complete and long-lasting sympathectomy, and the ileum examined. Changes in the levels of noradrenaline, neuropeptide Y, calcitonin gene-related peptide, substance P and vasoactive intestinal polypeptide in the external muscle layers containing the myenteric plexus of the ileum were determined between 6 and 20 weeks of age. After sympathectomy, noradrenaline levels were initially depleted (3% of age-matched controls at 6 weeks, P < 0.001, and 18% of age-matched controls at 12 weeks, P < 0.001), but were not significantly reduced at 20 weeks (67% of age-matched controls). Such increases in noradrenaline content with time after sympathectomy did not occur in the mesenteric vein (levels in 20-week-old sympathectomized rats were 2% of the control values (P < 0.001). In the myenteric plexus, catecholamine fluorescent nerve fibers were seen in the 12-week-old sympathectomized rats, although tyrosine hydroxylase-immunoreactivity was absent. Guanethidine sympathectomy had no effect on the neuropeptide levels in 6-week-old rat ileum but there was a selective increase at 20 weeks; the levels of calcitonin gene-related peptide and substance P were increased (X3, P < 0.001 and X1.6, P < 0.05, respectively) while vasoactive intestinal polypeptide and neuropeptide Y levels were unchanged. Short-term sympathectomy (destruction of sympathetic nerve terminals by acute 6-hydroxydopamine treatment) had no affect on noradrenaline or peptide levels in this tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic Fibers↗

Effects of acrylamide on cotransmission in perivascular sympathetic and sensory nerves.

The effects of chronic administration of acrylamide on sympathetic and sensory nerves were examined in the mesenteric artery of rabbits. The noradrenaline (NA) content of the artery was significantly decreased and the total contractile response to electrical field stimulation (4-64 Hz) markedly reduced in the acrylamide group. This was not due to an impairment of the contractility of the smooth muscle or to alterations in the postjunctional receptors. At 16 Hz, only the purinergic component of sympathetic cotransmission was significantly reduced by acrylamide. At 64 Hz, both the purinergic and the adrenergic components were significantly decreased. Field stimulation of the artery pretreated with guanethidine and precontracted with NA produced a frequency-dependent relaxation which was prevented by capsaicin and thus mediated by perivascular sensory nerves. In contrast to its effects on sympathetic cotransmission, acrylamide resulted in a trend, although not significant, towards increased responses at each frequency studied (2-16 Hz). 2-Methylthio-ATP (2Me-S-ATP) caused significantly greater relaxation following acrylamide treatment while vasodilator responses to calcitonin gene-related peptide and substance P were unchanged. It is concluded that, in addition to its known action in producing neuropathy in myelinated somatic motor and sensory nerves, acrylamide causes damage to unmyelinated perivascular sympathetic fibres. Purinergic mechanisms may be particularly susceptible to acrylamide since both the purinergic component of sympathetic vasoconstriction and the relaxation in response to 2Me-S-ATP were affected by acrylamide treatment.

Acrylamide↗

Maturational changes in sympathetic and sensory innervation of the rat uterus: effects of neonatal capsaicin treatment.

The plasticity of the sympathetic and sensory innervation of the rat uterus was examined, before and after puberty, in controls and in animals where primary sensory nerves had been destroyed by neonatal capsaicin treatment. Immunohistochemical and histochemical methods were used in association with nerve density measurements and biochemical assays. The main findings were as follows: (1) Puberty was associated with a marked increase in the weight of the uterine horn, uterine cervix and parametrial tissue. This was unaffected by capsaicin treatment. (2) The sympathetic innervation of the uterine horn and parametrial tissue was reduced following puberty as revealed by a decrease in the density of noradrenaline-containing nerves and a marked decrease in the tissue concentration of noradrenaline. Sympathetic nerves supplying the uterine cervix and the blood vessels of the uterus appeared to be unaffected by puberty. (3) In contrast, the sensory supply of the uterus by substance P and calcitonin gene-related peptide-containing nerves increased in parallel with uterine growth during puberty resulting in no change in nerve density and only a slight reduction in peptide concentration. (4) Neonatal capsaicin treatment caused a long-lasting depletion of substance P- and calcitonin gene-related peptide-containing nerves. In the uterine horn and parametrial tissue, capsaicin-resistant calcitonin gene-related peptide, but not substance P, still increased with tissue weight during puberty, indeed, in the uterine horn, the relative increase was greater than in controls. (5) Sensory denervation resulted in an increase in the non-vascular sympathetic supply of the uterus, although there was a regional variation in the time course of the response. Perivascular sympathetic nerves were unaffected by capsaicin treatment. The pattern of change in non-vascular noradrenaline-containing nerves associated with puberty was similar in nature to controls. Thus, there is considerable plasticity in the innervation of the uterus both during puberty and following sensory denervation. A complex pattern of change occurs with differential responses in vascular and nonvascular nerves and in different regions of the uterus. Such differences may be due in part to the different origins of individual nerve populations and/or to their relative sensitivities to sex hormones.

Animals↗