The metabolic cost of various occupational exposures.
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Adult↗
Biomedical subjects
M Pope
Publications and source records attributed to M Pope.
Modification of work organization.
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Adolescent↗
Conformations of complexes derived from the interactions of two stereoisomeric bay-region 5-methylchrysene diol epoxides with DNA.
The reaction mechanisms of two isomeric bay-region diol epoxides of 5-methylchrysene (trans-1,2-dihydroxy-anti-3,4-epoxy-1,2,3,4-tetrahydro-5-methylchrysene (DE-I) and trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydro-5-methylchrysene (DE-II) with double-stranded DNA in aqueous solutions were studied utilizing kinetic flow dichroism and fluorescence techniques. As in the case of the previously studied benzo(a)pyrene-7,8-diol-9,10-oxide isomers (BaPDE), both DE-I and DE-II rapidly form intercalation-type complexes (association constants K = 2700 and 1500 M-1 respectively in a neutral 5mM phosphate solution). The physically bound diol epoxide molecules react on time scales of minutes to form predominantly tetraols; a greater fraction (6 +/- 1%) of DE-I than of DE-II (2-3%) molecules react with the DNA to form covalent products. The DE-II isomer is characterized by a greater reactivity than DE-I, and the rates of reaction are markedly accelerated in the presence of DNA in both cases. The linear dichroism spectra of the covalent adducts reveal that the conformations of both types of adducts are similar, with the long axes of the phenanthrenyl chromophores tilted, on the average, at angles of 38-52 degrees with respect to the average orientations of the transition moments (at 260 nm) of the DNA bases. The conformations of the covalently bound DE-I and DE-II molecules resemble those observed in the case of the highly tumorigenic (+) enantiomer of anti-BaPDE.(ABSTRACT TRUNCATED AT 250 WORDS)
Binding Sites↗
Reaction mechanisms of trans-9,10-dihydroxy-anti-7,8-epoxy-7,8,9,10-tetrahydro-3-methylcho lan threne with DNA in aqueous solutions. Conformation of adducts.
The reaction mechanisms of trans-9,10-dihydroxy-anti-7,8-epoxy-7,8,9,10-tetrahydro-3-methylcholanth rene (anti-3-MCDE) in aqueous phosphate buffer solutions (pH 7, 24 degrees C) containing double-stranded DNA, and the structure of the covalent adduct formed, were studied by utilizing the techniques of absorption, fluorescence and linear dichroism spectroscopy. The results were compared with those obtained with the widely studied trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BaPDE). The reaction mechanisms are similar in both cases since 3-MCDE also appears to form physical complexes which give rise to an acceleration of the rate of reaction of the diol-epoxide (by as much as a factor of 30 at pH 7, depending on the DNA and salt concentrations). While in the case of 3-MCDE the physical association constant is about four times lower, and the overall rate of reaction is at least five times smaller (depending on the DNA concentration) than in the case of BaPDE, the level of covalent binding is two times higher (18 +/- 2% of the 3-MCDE molecules appear as covalent adducts, the remainder forming hydrolysis products). In a novel extension of flow linear dichroism techniques, it is shown that the orientations of small aromatic moieties bound to DNA whose absorption spectra overlap with those of the nucleic acid residues below 300 nm can be studied; the dichroism at 265 nm resulting from the anthracene-like aromatic residue of 3-MCDE covalently bound to DNA suggests that its long axis tends, on average, to be tilted away from the average orientations of the planes of the nucleic acids. This conformation is similar to the one observed with adducts derived from the covalent binding of the highly tumorigenic (+) enantiomer of BaPDE, while the adducts derived from other biologically less active stereoisomers of BaPDE are characterized by conformations in which the aromatic moieties tend to be more parallel to the planes of the nucleic acid bases. Differences in the biological activities of the various polycyclic aromatic diol-epoxides are discussed in terms of these conformations and the abilities of these molecules to bind covalently to DNA.
Animals↗
Control of leucocyte infiltration into the decidualized mouse uterus.
Ovariectomized mice were treated with oestrogen and progesterone on a schedule to mimic early pregnancy. Decidualization was induced with oil and uteri were examined at various times after the last progesterone injection. The first morphological change detected in the uterus of decidualized mice following withdrawal of progesterone was infiltration of leucocytes into the stroma. This preceded overt tissue breakdown and extravasation of blood cells, and did not occur following withdrawal of progesterone without decidualization. It is suggested either that there is a release of a chemoattractant from decidual cells before any morphological changes are apparent or that the signal for attracting the leucocytes is released at the time of decidual induction, but that their migration is suppressed by progesterone.
Animals↗
Leishmania donovani: surface membrane acid phosphatase blocks neutrophil oxidative metabolite production.
We show that a purified preparation of the prominent tartrate-resistant acid phosphatase (E.C.3.1.3.2), isolated from the external surface of the intracellular parasite Leishmania donovani (promastigote form), inhibits toxic oxidative metabolite production of neutrophils. Preincubation of a neutrophil suspension (2.5 X 10(6) cells/ml) for 15 min at 37 C with 250 units (1 unit equals 1 nmole of 4-methylumbelliferyl phosphate cleaved per hr at pH 5.5) of the acid phosphatase in Krebs-Ringer phosphate buffer (pH 7.4) decreased O2 consumption, O2- production, and H2O2 production of N-formyl-methionyl-leucyl-phenylalanine (fMet-Leu-Phe)-stimulated neutrophils to 15-25% of control values. The acid phosphatase also affected concanavalin A-stimulated O2-production by neutrophils, but had no effect on the rate of phorbol myristic acetate-stimulated O2- production, chemotactic peptide binding, degranulation, or membrane depolarization. Addition of an acid phosphatase inhibitor (Complex E; (NH4)6[P2Mo18O62] X 9H2O) to suspensions of opsonized promastigotes and neutrophils resulted in a threefold or greater enhancement of O2- production. These results suggest a possible pathophysiologic role for the acid phosphatase of L. donovani promastigotes.
Acid Phosphatase↗
Reaction mechanisms of trans-1,2-dihydroxy-anti-3,4-epoxy-1,2,3,4-tetrahydro-5-methylchrysene with DNA in aqueous solutions.
Reactions of trans-1,2-dihydroxy-anti-3,4-epoxy-1,2,3,4-tetrahydro-5-methylchrysene (anti-5-MeCDE) with DNA and the effects of ionic strength on the reaction were studied in aqueous buffer solution (5 mM sodium phosphate, pH 7) by means of absorption and fluorescence spectroscopy. The results are compared with those obtained with the widely studied metabolite model compound trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BaPDE). The rate constant of hydrolysis of 5-MeCDE is k = 1.0 X 10(4)/S, which is approximately 35 times smaller than the value of k for BaPDE under similar conditions. As in the case of BaPDE, the rate of reaction of 5-MeCDE is accelerated in the presence of DNA. This effect is attributed to the rapid formation of physical association complexes (binding constant K) and the subsequent slower formation (rate constant k3) of carbocations at DNA binding sites, which in turn decay rapidly via hydrolysis to tetraols (1,2,3,4-tetrahydroxytetrahydro-5-methylchrysene, 5-MeCT) and to covalent adducts. The values of K and k3 are 2800 +/- 300/M and 8.7 X 10(-3)/S respectively, and are reduced to 450 +/- 100/M and 1.8 X 10(-3)/S in the presence of 0.1 M NaCl. The fraction of 5-MeCDE molecules which bind covalently to DNA is, on the other hand, constant under these conditions and lies in the range of 5-8%. Similar values for the covalent binding are observed for BaPDE, even though the physical association constant K is approximately 10 times larger than for 5-MeCDE under similar conditions. This difference in the values of K are attributed to the larger aromatic ring system in BaPDE which allows for a higher interaction of this molecule with the bases of DNA. Finally, the tetraol derived from the hydrolysis of 5-MeCDE also binds non-covalently to DNA, but the value of K is approximately 3 times smaller than for the diol epoxide.
Carcinogens↗
Lumbar paraspinal compartment syndrome. A case report with physiologic and anatomic studies.
A 24-year-old man presented with severe low-back pain and paraspinal muscle spasm after exertion. Elevation in temperature, white blood cell count, serum muscle enzymes, and urine myoglobin, as well as computer tomographic evidence of paraspinal muscle edema and necrosis, were present. No etiology could be documented, and the possibility of an acute exertional compartment syndrome was entertained. Subsequently, cadaveric dis-sections indicated that the erector spinae muscles are contained within a well-developed fascial sheath. Continuous slit catheter pressure measurements within this compartment in eight healthy male subjects were subsequently carried out. These indicated a physiologic behavior similar to other known compartments for which compartment syndromes have been described. Variation in intracompartmental pressure occurred as a function of body posture, erector spinae isometric contraction, and active intra-abdominal pressurization. We suggest this patient had a paraspinal compartment syndrome and have described pressure characteristics of this compartment in normal men.
Adult↗
Structural effects in reactivity and adduct formation of polycyclic aromatic epoxide and diol epoxide derivatives with DNA: comparison between 1-oxiranylpyrene and benzo[a]pyrenediol epoxide.
Reaction of 1-oxiranylpyrene (1-OP) with DNA and the structures of the covalent and noncovalent complexes formed were studied in aqueous media (5 mM phosphate buffer with 0.1 M NaCl, pH 7) by utilizing the techniques of absorption, fluorescence and linear dichroism spectroscopy in order to gain an understanding of possible structure-activity relationships for polycyclic aromatic hydrocarbon epoxides in tumorigenesis and carcinogenesis, and the results were compared with those obtained for the highly active benzo[a]pyrene diol epoxide (BaPDE). Like BaPDE, 1-OP undergoes acid-catalyzed hydrolysis with the pseudo-first-order rate constant k = 4.6 X 10(-4) s-1 in the absence of DNA, which is about 10 times slower than in the case of BaPDE. In DNA solutions, this hydrolysis is catalyzed by a rapid formation of a physically bound complex of 1-OP-DNA, which subsequently undergoes either (1) hydrolysis to a diol derivative or (2) formation of a covalent adduct of 1-OP-DNA. The same value of the noncovalent binding constant (K = 4000 M-1 is obtained for both 1-OP and for BaPDE, which suggests that the pi-electron interaction between the pyrenyl moiety and the nucleic acid bases is the dominant factor in the formation of the physical complexes and that the two extra OH groups in BaPDE do not play a significant role in determining the value of the physical binding constant.(ABSTRACT TRUNCATED AT 250 WORDS)
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
Vascular and cellular changes in the decidualized endometrium of the ovariectomized mouse following cessation of hormone treatment: a possible model for menstruation.
Ovariectomized mice were prepared for decidualization with oestrogen and progesterone and arachis oil injected into the uterine lumen. Hormone injections were then stopped and uteri examined at intervals between 31 and 84 h after the last progesterone injection. At 31 and 35 h the stroma showed a normal decidual reaction. Between 45 and 79 h the stroma underwent a series of changes which started with the congestion of dilated blood vessels with swollen erythrocytes followed by breakdown of the vessel walls and extravasation of blood. At the same time the decidual cells showed typical apoptotic changes and there was invasion by leucocytes. An outer ring of stroma did not take part in the degenerative process and eventually a central core of blood cells and degenerating decidual cells became detached and was shed into the lumen. Animals treated in exactly the same way but with the omission of the decidual stimulus did not show such changes in the stroma. It is suggested that the changes in the endometrium resemble those of menstruation and support the suggestion that for menstruation to occur the stroma must be differentiated for implantation. This occurs during the cycle in women but does not occur in non-primates unless a decidual stimulus is applied to the uterus.
Animals↗
The backbone and side chain conformations of the cyclic tetrapeptide HC-toxin.
A study of the conformational parameters of HC-toxin and its diacetyl derivative in chloroform solution has been carried out. Two-dimensional NMR spectroscopy and the nuclear Overhauser effect have been used in order to determine connectivities (assignments and sequence) and approximate torsion angles and interproton distances. The results are consistent with a bis-gamma-turn conformation previously reported for dihydrochlamydocin. Model building based upon NMR data supports a D configuration for Ala2 and Pro4 residues.
Magnetic Resonance Spectroscopy↗
How the elephant got its trunk.
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Animals↗
Strain measurement in the medial collateral ligament of the human knee: an autopsy study.
A strain transducer was developed which employs a magnetic field sensing device to detect linear displacement. The transducer was attached to the medial collateral ligament (MCL) of human autopsy specimens, minimally influencing their physiologic behavior. A strain 'map' of the MCL as a function of knee flexion (full extension to 120 degrees) both with and without abduction force was obtained. Our investigation revealed consistent differences in the strain patterns between proximal, middle and distal segments of the anterior and posterior borders of the MCL. Anatomic variations in the pattern of collagen fibers within the MCL, interactions between posterior oblique capsular fibers and the MCL, and the skeletal configuration may account for these varied strain patterns.
Humans↗
Transcutaneous muscle stimulation to retard disuse atrophy after open meniscectomy.
Immobilization of an extremity inevitably results in disuse muscle atrophy. The effectiveness of transcutaneous muscle stimulation by a portable device in preventing atrophy has been determined. Ten patients treated by open meniscectomy and given the usual isometric training were matched with ten patients in whom electrostimulation, consisting of a strong, tetanizing, five-second sustained muscular contraction about 400 times/day, was used for two weeks. Muscular strength and leg circumference were measured before surgery and four weeks after surgery. The electrically stimulated group had a significantly smaller loss of muscle volume and muscle strength, were able to walk earlier without crutches, had a greater range of knee motion, had much less postoperative knee swelling, and used significantly less pain medication. Transcutaneous electrical stimulation may prevent muscle atrophy due to immobilization, thereby shortening rehabilitation time.
Adult↗
An example of a naturally occurring anti-cE (Rh27) that binds complement.
A serum sample from a nontransfused male containing anti-Rh27 and an additional weakly reacting antibody was investigated. One absorption of the serum with RZR1 cells left only anti-Rh27 while repeated absorption with R1R1 cells or autologous cells had no effect. Treatment of the serum with reducing agents destroyed all activity suggesting the antibody was predominantly IgM. Tests with monospecific antiglobulin reagents in the indirect antiglobulin test revealed very weak reactions with anti-IgM and anti-IgA, no reactions with anti-IgG, and strong reactions with anti-C3(C3c + C3d) and anti-C4. This is the first reported example of a naturally occurring complement binding anti-Rh27.
Absorption↗
Transcutaneous muscle stimulation as a method to retard disuse atrophy.
Thirty healthy, young adults (18 to 25 years of age), were volunteers in a three-group study to determine the efficacy of transcutaneous electrostimulation as a means of preventing atrophy of normal musculature on wearing a long-leg cast. Each group of ten subjects (five males and five females) were chosen by lot: Group I, nonisometric, Group II, isometric, Group III, TMS electrostimulated thigh and calf muscles. There was little difference in the findings in Groups I and II, and each lost an appreciable amount of muscle mass and power after just two weeks of immobilization. However, in the electrostimulated group muscle atrophy was one-half that of the other groups in the thigh area and one-fifth that of the others in the calf area. In addition, the calf musculature retained its bulk and power with actual increase in a few of the less athletic individuals. Trancutaneous muscle stimulation offers great promise for surgically treated or impaired extremities, enabling early return to activity with optimal function.
Adolescent↗
Patient needs on admission.
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Equipment and Supplies, Hospital↗