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Mutagenicity of products from coal gasification and liquefaction in the Salmonella/microsome assay.

As a first step in the assessment of their possible bio-effects, coal-related materials were tested for mutagenicity in the Salmonella/microsome assay. Of three coal gasification by-products tested, only a tar was mutagenic for any of four Salmonella strains. The following liquefaction materials were mutagenic for strains TA1538, TA98, and/or TA100: A liquefaction vehicle oil and coal hydrogenation filtered liquid, separated bottoms, vacuum overhead, and vacuum bottoms. Neither powdered coal nor water produced as a by-product of the hydrogenation process was positive in the Salmonella test. No coal-related material was mutagenic for the missense mutant TA1535 or for any strain in the absence of metabolic activation provided by rat hepatic homogenates (S9). In all but one instance Aroclor 1254-induced S9 provided the maximum activation for mutagenesis. Fractionation of all samples was undertaken by serial extraction with organic solvents of increasing polarity (hexane, toluene, methylene chloride, acetonitrile). Highly mutagenic materials were found in fractions of the hydrogenation filtered liquid, vacuum overhead, and vacuum bottoms. Thus far non-mutagenic samples have not yielded mutagenic components upon fractionation.

Animals↗

Cytokeratin intermediate filaments of rat hepatocytes: different cytoskeletal domains and their three-dimensional structure.

A new method of visualizing the three-dimensional architecture of the cytokeratin filaments of the intact rat hepatocyte in situ has been achieved. Frozen sections of liver cut 10 micron thick were serially extracted to remove all elements of the cells except the intermediate filaments. Parallel sections were stained with monoclonal antibodies to the two main cytokeratins found in bile duct and liver cells. Immunofluorescent antibody and immunogold electron microscopy techniques were used to identify the proteins morphologically. Several new observations resulted from these studies. The pericanalicular sheath of intermediate filaments was visualized using steropairs as an uninterrupted branching tubular structure composed of cytokeratins located in the cell cortex of adjacent hepatocytes. Intermediate filaments in the cell cortex formed a distinct sheet of matted filaments which enveloped the entire hepatocyte. The cortical intermediate filaments were in continuity with the pericanalicular sheath and the filaments located within the cytoplasm. The intermediate filaments are attached to the centrioles and appeared to tent the nuclear lamina-pore complex at points of contact. Monoclonal antibodies to rat liver intermediate filament cytokeratins (CK49 and CK55) each stained intermediate filaments located in the cell cortex, within the cytoplasm and at the nucleus. By immunogold staining, some of the intermediate filament filaments were shown to contain both cytokeratins. Filaments which did not stain were thought to be either actin at the cell periphery or nuclear lamins around the nucleus. It is concluded that the cytokeratins form a specialized framework for the cell cortex, canaliculus, centrioles and the nucleus of hepatocytes. The filaments run continuously throughout the cytoplasm without terminating.

Animals↗

The cell wall subproteome of Listeria monocytogenes.

The surface subproteome of Listeria monocytogenes that includes many proteins already known to be involved in virulence and interaction with host cells has been characterized. A new method for the isolation of a defined surface proteome of low complexity has been established based on serial extraction of proteins by different salts at high concentration, and in all 55 proteins were identified by N-terminal sequencing and mass spectrometry. About 16% of these proteins are of unknown function and three proteins have no orthologue in the nonpathogenic L. innocua and might be involved in virulence mechanisms. Remarkably, a relatively high number of proteins with a function in the cytoplasmic compartment was identified in this surface proteome. These proteins had neither predicted or detectable signal peptides nor could any modification be observed except removal of the N-terminal methionine. Enolase (Lmo2455) is one of these proteins. It was shown to be present in the cell wall of the pathogen by immunoelectron microscopy and, along with heat shock factor DnaK (Lmo1473), elongation factor TU (Lmo2653), and glyceraldehyde-3-phosphate dehydrogenase (Lmo2459), it was found to be able to bind human plasminogen in overlay blots and surface plasmon resonance (SPR) experiments. The KD values of these interactions were determined by SPR measurements. The data indicate a possible role of these proteins as receptors for human plasminogen on the bacterial cell surface. The potential role of this recruitment of a host protease for extracellular invasion mechanisms is discussed.

Aminopeptidases↗

Modified amyloid beta protein ending at 42 or 40 with different solubility accumulates in the brain of Alzheimer's disease.

Serial extraction study of Alzheimer's disease (AD) and control brains revealed 4, 3.7 and 3 kD amyloid beta protein (A beta) species accumulated in AD brains. In the fractions extracted with TBS, 10% SDS and formic acid, considerable amounts of A beta species were recovered in SDS fractions besides TBS and formic acid fractions. Immunoblotting with several site-specific antibodies confirmed not only the presence of 4 kD A beta starting at the first amino acid of A beta but also 2 smaller A beta species with modification of their amino-termini in the highly resolutional Tris/Tricine gel system. A beta solubility using these solvents was associated with both modification of the amino-terminus and length of carboxyl-terminus of A beta. Especially, a large amount of modified A beta was found to be accumulated as forms with different solubility in AD brains.

Aged↗

Elastin is increased in abdominal aortic aneurysms.

The decrease in elastin concentration in abdominal aortic aneurysm (AAA) has been ascribed to elastolysis. The discordant response of the elastin and collagen genes in AAA suggests a different explanation: dilution of elastin because of higher levels of synthesis of collagen and other matrix proteins. The purpose of this study was to determine circumferential content of elastin, collagen, and total protein in aneurysmal (AAA), atherosclerotic, and normal (NL) infrarenal aorta. Standard serial extraction techniques of complete 1-cm rings of midinfrarenal aortic tissue were used to remove soluble protein, calcium, and lipids. Hydroxyproline (collagen), desmosine/isodesmosine (elastin), and total amino acid (total protein) content were determined by amino acid analysis. Means values (+/- SEM) were compared by ANOVA. Circumferential content of desmosine/isodesmosine was increased 2.5-fold in AAA compared to NL (P < 0.05). Collagen and total protein were increased 5.7- and 4.7-fold, respectively (P < 0.05). There was a high degree of correlation between circumference and collagen content (r = 0.89). These data demonstrate that significant synthesis of matrix proteins accompanies aortic dilatation. While both elastin and collagen are increased, there is a much greater increase in circumferential collagen content than elastin content. These data do not preclude proteolysis as a factor in AAA but suggest that the decrease in elastin concentration results from dilution of elastin by a greater increase in the synthesis of other matrix proteins and that synthesis is an important factor in AAA formation.

Adult↗

Physico-chemical and immunological characteristics of pituitary prolactin from water buffaloes (Bubalus bubalis).

Prolactin (PRL) was purified from freshly frozen pituitary glands of water buffaloes (Bubalus bubalis) by a combination of existing procedures of Ellis and Jiang and Wilhelmi involving serial extraction of different pituitary proteins. The partially purified preparation was further fractionated on DEAE-Sephadex followed by Sephadex G-100 chromatography. This was finally purified on HPLC. This preparation was found to be homogeneous by SDS-PAGE and HPLC and had a single N-terminus amino acid (Threonine). The molecular size was estimated to be 24K +/- 0.5 by SDS-PAGE and approximately 25K by GPC-HPLC. The buffalo PRL gave a dose dependent inhibition curve in a rat liver based radio receptor assay with a potency of 30-35 I.U./mg and also in a partial homologous RIA using 125I-buffalo PRL and rabbit anti-oPRL serum giving a potency of 30 I.U./mg. Metabolic labelling studies using 35SO4(2-) with buffalo pituitary minces showed the incorporation of radioactive sulfate into immunoprecipitable PRL-like material. Physico-chemical characterization of the site of the linkage between sulfate and PRL revealed the presence of Tyr-O-SO4 in bu-PRL. A high affinity monoclonal antibody (MAB) with Ka of 10(10) L/M, belonging to IgG1 isotype, and capable of cross reacting with ovine and bovine PRL was generated. This MAB was conformation specific as reduced and carboxymethylated PRL did not react with it. A homologous RIA system using this MAB has been standardised.

Animals↗

Investigation on Semecarpus Lehyam--a Siddha medicine for breast cancer.

The use of complementary and alternative medicines for breast cancer patients has been increasing every year. Traditional Indian systems of medicine, such as Siddha, have been reported to benefit patients in India through herbal interventions for cancer. One such herbal medicine is Semecarpus Lehyam (SL), and this study aims at providing a scientific basis for the anti-tumor property of SL with respect to breast cancer. SL was subjected to serial extraction with four organic solvents of increasing polarity (n-hexane, chloroform, ethyl acetate, n-butanol and water). The solvents from all fractions were removed, dried and dissolved in dimethyl sulfoxide for testing their anti-tumor activity against two breast cancer cell lines, MCF-7 [estrogen receptor (ER)-positive] and MDA 231 (ER-negative) using cell viability and apoptosis assays. The most potent SL fractions were also combined with radiation and doxorubicin to determine the radio- and chemo-sensitizing effects of SL on these breast cancer cell lines. In terms of cytotoxicity as well as induction of apoptosis, the n-hexane and chloroform fractions of SL were more significantly active against MDA 231 cells than MCF-7 cells. The n-butanol fraction of SL showed some activity against MCF-7 cells. When combined with radiation or doxorubicin, the n-hexane and chloroform fractions enhanced the radio-sensitivity (11.8-fold) and chemo-sensitivity (6.5-fold) of MDA 231 cells. This study demonstrated SL to be a potent anti-tumor agent against the ER-negative breast cancer cell line. The study is also the first step in the scientific validation of SL for use against breast cancer, particularly the ER-negative type.

Antibiotics, Antineoplastic↗

Morphologic changes in the transverse dimension using the Fränkel appliance.

Anthropologic studies have shown that the incidence of malocclusion increases as societies become urbanized. Crowding seems to be one of the most common findings. Possible explanations for this have been heredity, dietary changes, poor eruption patterns, and mouth breathing, among others. Many clinicians begin treatment early in order to minimize this maldevelopment. Various early-treatment approaches have included serial extraction, lingual holding arches, palatal expansion, functional appliances, partial fixed appliances, and headgear. Expansion with the functional regulator offers one solution to crowding. If this expansion can be shown to be significant in amount and stable, then the Fränkel appliance merits consideration regardless of the clinician's choice of fixed appliances. Fifty patients treated with the Fränkel appliance from the private practice of the author were analyzed to evaluate changes in the transverse dimension. The ages ranged from 5.9 to 13.8 years, with the average age 9.6 years (+/- 1.54). Twenty-nine patients were girls and twenty-one were boys. The Angle molar relationships were distributed as follows: Class I-21 patients; Class II-27 patients; and Class III-2 patients. All patients were Caucasians and were selected for treatment on the basis of the presence of crowding, excessive overjet or overbite, or excessive open-bite. The presence of crowding was determined by a study model and Panorex analysis. All patients reported in this study were considered cooperative and wore their appliances for approximately 20 hours per day. Five cephalometric measurements were taken: nasal cavity width, maxillary width, mandibular width, intercanine width, and intermolar width. All cephalograms were originally traced by the same technician at Rocky Mountain Data Systems, Inc. When there was a discrepancy between the RMDS tracing and the author's tracing, the author's tracing was used. Data to serve as controls were provided by Rocky Mountain Data Systems, Inc. The sample is based on forty children measured over a 5-year period between the ages of 8 and 13 years. Twenty patients had an Angle Class I molar relationship, and twenty patients had an Angle Class II molar relationship. Two Student's t statistics were used to evaluate these measurements. Means, standard deviations, and standard errors are shown. The Bonferroni inequality method is used to determine if these five measurements are significant, and all five measurements were simultaneously significant at the 0.05 level. From the statistical results as well as the cephalometric descriptive analyses, it appears that the Fränkel appliance precipitates a limited but potentially significant increase in arch length which will benefit the patient if the results are stable.

Activator Appliances↗

Suppression of cholesterol biosynthesis by constituents of barley kernel.

Hepatic beta-hydroxy-beta-methylglutaryl CoA (HMG-CoA) reductase, cholesterol 7 alpha-hydroxylase (7 alpha-hyd), and fatty acid synthetase (FAS) activities and cholesterol levels were determined in chicks fed isonitrogenous corn- and high-protein barley flour (HPBF) based diets. HMG-CoA reductase (-27%), 7 alpha-hyd (-30%), and serum cholesterol (-13%) were reduced, whereas FAS increased (28%) in comparison to a corn-based (control) diet. fractions obtained by serial extractions of HPBF with solvents of increasing polarity were fed at levels equivalent to 20% HPBF in a corn-based diet to female White Leghorn (WHL) chickens for 3 weeks. A petroleum ether-soluble fraction of HPBF produced 3 effects: an increase in body weight (18%), a strong suppression of HMG-CoA reductase (-36%) and FAS (-40%) accompanied by decreases in serum triglyceride (-9%) and cholesterol levels (-23%). The methanol-soluble fraction produced a significant suppression of HMG-CoA reductase (-49%) and serum cholesterol level (-29%), and an increase in FAS activity (95%). These effects were duplicated in 7-week-old broiler chickens which also showed a significant decrease in chol-LDL (low density lipoprotein) levels by these fractions. The factor(s) lowering serum cholesterol concentration was about equally divided between the polar and nonpolar fractions, and each was significantly more effective than the 20% HPBF in the corn-based diet. The observed effects on lipogenesis and cholesterogenesis might be attributed to a number of chemical constituents of HPBF, but cannot be attributed to the water-insoluble plant fibers.

Animals↗

The annexin II2p11(2) complex is the major protein component of the triton X-100-insoluble low-density fraction prepared from MDCK cells in the presence of Ca2+.

Annexin II2p11(2) is present in the submembranous region of cells expressing both subunits of the complex. Most probably, this subcellular distribution is maintained through the interaction of annexin II2p11(2) with membrane phospholipids and/or elements of the cortical cytoskeleton known to occur in vitro in a Ca(2+)-dependent manner. To determine whether membrane or cytoskeleton interactions are primarily responsible for anchoring annexin II2p11(2) in the cell cortex, we subjected Madin-Darby canine kidney (MDCK) cells to serial extractions using different detergents and identified annexin II and p11 in the different fractions employing specific antibodies. The complex but not monomeric annexin II remains insoluble when the cells are extracted with Triton X-100 in the presence of Ca2+. However, treatment of the Triton X-100-insoluble cell remnants with a series of other detergents known to solubilize GPI-anchored proteins leads to a partial extraction of annexin II2p11(2) even in the presence of Ca2+. Using sucrose density gradient analysis in the presence of Ca2+ as a different means of fractionating the Triton X-100-insoluble cell remnants we show that the majority of annexin II2p11(2) copurifies with a low-density fraction which has been reported to contain GPI-anchored proteins, certain glycolipids, and VIP21/caveolin. Annexin II2p11(2) is by far the most abundant protein component in this fraction indicating that its association with the low-density material occurs via lipid binding and is not due to the interaction with a certain protein.

Animals↗

Identification of a silver binding protein associated with the cytological silver staining of actively transcribing nucleolar regions.

Nucleoli isolated from Novikoff hepatoma cells were stained with AgNO3 to demonstrate the typical staining of active ribosomal cistrons. Pre-treatment of the nucleoli with 80 mM Tris-HCl (pH 7.5) -- 2.0 M NaCl did not interfere with silver staining. Treatment of the nucleoli with 80 mM Tris-HCl (pH 7.5) -- 0.15 M NaCl did, however, eliminate silver binding. Serial extraction of nucleoli with 2.0 M NaCl buffer followed by 0.15 M NaCl buffer also abolished silver staining. Analysis of the supernatant fraction of these extracts by polyacrylamide gel electrophoresis indicates that, although more than one nucleolar protein can bind silver, only one protein is associated with the staining of active ribosomal cistrons.

Animals↗

Deposition and selective degradation of structurally-abnormal type I collagen in a collagen matrix produced by osteogenesis imperfecta fibroblasts in vitro.

Collagen matrix deposition and turnover were studied in skin fibroblasts from a control and from a patient with lethal perinatal osteogenesis imperfecta (OI) identified as a Gly667 to Arg substitution in the alpha 1(I) chain. A culture system where ascorbic acid was included to stimulate collagen matrix formation over extended culture periods was used. Serial extraction of the control cell collagen matrix confirmed that a substantial mature crosslinked collagen matrix was formed in the control fibroblast cell layer. In contrast, total collagen deposition by the OI fibroblasts was poor, with the quantity of collagen deposited only about a quarter of that of the control cells. Detailed analysis of the OI fibroblast matrix revealed that the mutant collagen chains were incorporated into the collagenous matrix. These data indicate that, when grown with ascorbate in long-term culture, OI fibroblasts reproduced the abnormal matrix deposition pattern of OI tissues in vivo. The overall dramatic reduction in collagen matrix formation was not accounted for by reduced collagen production, since during the period of matrix deposition (days 8-12) the rate of production by the OI cells was only slightly less than that of the control cells. The incorporation of the newly-synthesized OI collagen into the matrix was less efficient than in control cells, reflecting the cooperative nature of matrix deposition. The fate of this mutant collagen containing the Gly to Arg charge-change was followed in the matrix by a pulse-chase experiment and two-dimensional electrophoresis. These data demonstrated that the mutant incorporated into the matrix was unstable, with the proportion of mutant declining during the chase. The deposition of the mutant monomers into a pool more accessible to proteolytic degradation indicated that the mutant and normal collagens did not copolymerize to form collagen fibers of even collagen distribution, but rather the mutant collagen was either enriched on the exposed surfaces of mixed-composition fibers, or was unable to form copolymers efficiently and polymerized into mutant-only fibrillar assemblies more prone to proteolytic attack.

Collagen↗

The distribution of soluble, mineral-bound, and matrix-bound proteins in osteoporotic and normal bones.

Very little is known about the composition of noncollagenous protein (NCP) in osteoporotic bone. We have obtained osteoporotic (OP) cancellous bone samples from 2-4 cm below the surface of human femoral heads and compared the protein profiles to age-matched (old controls, OC), as well as young autopsy controls (YC). The proteins were analyzed using a serial extraction method which liberates proteins from distinct pools; first, proteins were extracted in 4.0 M GuHCl (G1), followed by the extraction of mineral-bound protein with 0.5 M EDTA (E), and finally the protein previously masked by the mineral was released by a second 4.0 M GuHCl extraction (G2). The tissue residue was digested with bacterial collagenase liberating proteins bound to the collagenous matrix. Uniform bone preparations of finely ground bone powder were used for our study. The protein content of the four groups was determined together with the protein distribution using amino acid analysis and gel-electrophoresis. Our data indicate that the noncollagenous protein content is considerably reduced in osteoporotic bone when compared with age-matched or young controls, whereas the collagen content is unaffected. When bone proteins were investigated using gel-electrophoresis we found a similar distribution of proteins in the G1 and E fractions of all three groups, but the osteoporotic bone samples, using densitometric analysis of the gels, showed quantitative differences in a number of the proteins. The greatest differences were observed in the G2 extract, where the NCP of osteoporotic bone was limited to a few low-molecular-weight bands when compared with the OCs or YCs.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗

Development of a strontium-containing hydroxyapatite bone cement.

A new route was developed to synthesis a new type of strontium-containing hydroxyapatite (Sr-HAP) bone cement with precursors of tetracalcium phosphate (TTCP), strontium hydrogen phosphate (DSPA), dicalcium phosphate (DCPA), phosphate acid and water. The processing parameters and fundamental properties including pH value, setting time, compressive strength of final hardened body and the cytotoxicity for serial extracts of each cements were investigated. The result shows that the final product of the cement after setting for 24h is nonstoichiometic Sr-containing hydroxyapatite (Ca(10-m-x)Sr(x) square(m)(HPO4)y(PO4)6-y(OH)2-2m square2m, 0<x<1, nSr-HAP) and no other harmful impurities were detected. The pH value of Sr-containing cement pastes approaches to 7.0-7.6 when they are mixed with a ratio of 1:1 of powder to liquid (P/L) in weight. The setting time of the cement pastes is 4-11 min for the initial one and 10-17 min for the final one when the concentration of diluted phosphate is in a range of 0.5-1.0 mol/l. The compressive strengths of the hardened cements with different molar ratios of Sr/(Sr+Ca) after subjected an immersion in simulated body fluid (SBF) increase uniformly from 1 day to 5 days, where they get maximum values, respectively, but then decrease till to 2 weeks. Especially for the CPC-1, with a Sr/(Sr+Ca) molar ratios of 5% in cement powder composition, the largest compressive strength gained at 5 days is 66.57 MPa and the lowest one gained at 2 weeks is 44.75 MPa, which matches the value of human bones and can be expected to use in clinic application in repairing the nonloading sites on account of the positive result of cytotoxicity test of the extracts of Sr-containing calcium phosphate cement (Sr-CPC).

Animals↗

High-performance liquid chromatographic analysis of beta-carbolines in human scalp hair.

A chromatographic method was studied for the quantitation of beta-carbolines in hair as potent biomarkers. Under optimal conditions, human scalp hair was enzymatically digested to release analytes effectively. The hair digests were treated with fluorescamine before serial extractions to inhibit the artifactual production of beta-carbolines during analysis and purify them selectively, followed by reversed-phase high-performance liquid chromatography with fluorometric detection. Hair samples were found to contain beta-carboline and 1-methyl-beta-carboline, which were identified by tandem mass spectrometry, but not their reduced form 1,2,3,4-tetrahydro-beta-carboline and 1-methyl-1,2,3,4-tetrahydro-beta-carboline. Both beta-carboline and 1-methyl-beta-carboline were quantified in the concentration range of 0.1-10.0 ng/ml. Their mean recoveries from hair digests were 70-72%, and the intra- and inter-assay RSD ranged between 6.0 and 10.3% in spiking experiments with standards (1.0 ng/ml). When quantitatively analyzing scalp hair collected from alcoholics, smokers, non-smokers and autistics, beta-carboline and 1-methyl-beta-carboline showed the concentrations of ng/mg levels or less which characterized different hair samples. The proposed method will be useful for detecting the in vivo concentration changes of beta-carbolines associated with alcohol abuse, smoking behavior and neuropsychiatric disorder.

Alcoholism↗

Studies on the anti-inflammatory, antipyretic and analgesic properties of the leaves of Aegle marmelos Corr.

The serial extracts of the leaves of Aegle marmelos Corr. were investigated for anti-inflammatory property. The analgesic and antipyretic properties were also evaluated. The most of the extracts derived from the plant Aegle marmelos caused a significant inhibition of the carrageenan-induced paw oedema and cotton-pellet granuloma in rats. The extracts also produced marked analgesic activity by reduction the early and late phases of paw licking in mice. A significant reduction in hyperpyrexia in rats was also produced by the most of the extracts. This study was established anti-inflammatory, antinociceptive and antipyretic activities of the leaves of Aegle marmelos.

Acetic Acid↗

Congenital insensitivity to pain--review and report of a case with dental implications.

Pain is a protective mechanism for the body. Absence of pain is a symptom in several disorders, both congenital and acquired. The congenital types are present at birth and affect the number and distribution of types of nerve fibers. At present, 5 types of hereditary sensory and autonomic neuropathies have been identified. The various disorders within this group are classified according to the different patterns of sensory and autonomic dysfunction and peripheral neuropathy and the presence of additional clinical features such as learning disability. However, the field is currently moving away from classification based on clinical presentation toward classification based on underlying genetic abnormality. In the absence of pain, patients are at risk of late presentation with illnesses or injuries, and have an increased incidence of traumatic injury. Self-mutilation is an almost invariable feature of these disorders. We report the case of a patient with congenital insensitivity to pain that presented with self-mutilation injuries to his hands and oral tissues caused by biting. The severe nature of these injuries necessitated serial extraction of his primary teeth soon after eruption, which led to a cessation of the problem. The mutilation has not returned following the eruption of the first of his permanent teeth, suggesting that he has learned not to bite himself, even though to do so causes him no discomfort.

Bites, Human↗

Modulation of proliferation in epidermal keratinocyte cultures by lowered oxygen tension.

The modulation of proliferation and differentiation in primary epidermal keratinocyte cultures by lowered gas phase oxygen tensions was studied. Neonatal mouse epidermal keratinocyte cultures were grown in an Heraeus type B 5060 EK/O2 incubator in oxygen tensions between 5% and 15% (within the physiologic range); the oxygen tension of ambient air being 21%. Cell morphology was studied using histochemical stains and electron microscopy. Differentiation was assessed using autoradiography of SDS PAGE gels of six serially extracted cell protein fractions with [3H]leucine as a marker. Autoradiographs using [14C]glucosamine and 32Pi as markers were also assessed as a measure of other cell functions. Proliferation was studied using autoradiography of [3H]thymidine ([3H]TdR) pulse-labeled cultures and [3H]TdR incorporation into isolated DNA fractions. The results of these studies showed that lowering the oxygen tension in the gas phase reversibly inhibited cell proliferation. There was a direct arithmetic relationship between the proliferative rate of the cultures and the oxygen tension. No change in differentiation as defined by [3H]leucine indexing of protein synthesis was seen. Other markers of cell function, such as [14C]glucosamine glycosylation and [32P] phosphorylation of proteins were also unchanged. These results suggest that oxygen tension regulates only proliferation in epidermal keratinocytes. This epidermal response is well adapted to its role in the healing wound, and is an example of a tissue-specific modification of a regulatory function.

8-Bromo Cyclic Adenosine Monophosphate↗