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Biomedical subjects

M Pope

Publications and source records attributed to M Pope.

At least 73 records · Page 4Linked to original sources

The in vitro proliferative response of lymphoid cells of mice infected with Salmonella enteritidis 11RX.

Intraperitoneal injection of (BALB/c x C57BL/6) F1 mice with live, but not killed Salmonella enteritidis 11RX (11RX) induced T cells in the spleen and peritoneal cavity which were able to proliferate in vitro in response to two different forms of 11RX antigens. The majority of cells which proliferated were L3T4+ T cells and most of the response was restricted by the I-A locus of the H-2 major histocompatibility complex, although a smaller K region restricted response was also detected. T cells able to respond to 11RX antigens could only be demonstrated when non-adherent lymphoid cell suspensions from immunized mice were used, and usually a limited response was obtained unless small numbers of adherent cells present in normal peritoneal cell suspensions were added. Cells cultured in vitro for 3 days were able to mediate local transfer of delayed type hypersensitivity and secondary immunization did not enhance the reactivity of responding cells to 11RX antigens.

Animals

Pull-off strength of gardner-Wells tongs from cadaveric crania.

Failure of attachment ("pull-off") of Gardner-Wells tongs from the cranium occasionally occurs, and may cause problems, especially in cases of significant cervical spinal instability. The optimal method for Gardner-Wells tongs attachment is not well defined: the effect on pull-off strength of stem protrusion of the spring-loaded pin, and user accuracy in setting stem protrusion do not appear to be documented in the medical literature. The authors measured pull-off strength from five fresh cadaveric crania, for each of five stem protrusion settings. In a related experiment, staff surgeons were asked to follow the standard instructions for applying clinically available Gardner-Wells tongs (smooth, unmarked indicator stems on the spring-loaded pins), after which the actual stem protrusion lengths were recorded. When the indicator stem protruded 1.0 mm (manufacturer's recommendation), the mean pull-off strength (+/- standard deviation [SD] was 137 +/- 34 pounds (610 +/- 151 N). Even with stem protrusions as low as 0.25 mm, the lowest pull-off strength was 60 pounds. Failures of fixation occurring with traction loads of 35 to 50 pounds are almost surely associated with stem protrusions of less than 0.25 mm. Even without an indicator line on the stem at 1 mm, all of the 13 orthopaedists tested produced an actual stem protrusion of 0.37 mm or more. Secure attachment of larger cranial traction loads requires careful attention to pin tightening. Proper location on the skull and the risk of penetration through the inner table must also be kept in mind.

Biomechanical Phenomena

A biomechanical analysis of the Ilizarov external fixator.

Five configurations of the Ilizarov fixator were analyzed in vitro. The overall stiffness, shear stiffness, and axial motion of the fracture site were determined. The data were compared with the results of eight conventional one-half frame fixators previously tested in the same manner. The Ilizarov fixator allowed significantly more axial motion at the fracture site during axial compression than the other fixators tested. The overall stiffness and shear rigidity of the Ilizarov external fixator were similar to those of the one-half pin fixators in bending and torsion. The stability of the Ilizarov fixator was a function of bone position within the fixator rings and fixation wire tension. The use of olive stop wires increased the shear resistance of the Ilizarov system.

Biomechanical Phenomena

Neuropharmacologic effects of vibration on the dorsal root ganglion. An animal model.

The neuropharmacologic effects of low frequency vibration on the dorsal root ganglion, a reported epidemiological cause of low-back pain, have only recently been described. This investigation was undertaken to validate the hypothesis that substance P and VIP, known to be produced in the dorsal root ganglion cell bodies, will be affected by low frequency vibration. Three New Zealand white rabbits were vibrated at discrete frequencies (2-10 Hz) to determine the resonant frequency of the rabbit spine. The resonating frequency was in the (3.5-5.0 Hz) range. The peak amplitude was at 4.5 Hz. Ten female New Zealand white rabbits were then paired into two groups of five. One group served as a control and had exactly the same procedures performed as the experimental group except for the vibration. The L4-5 and L5-6 dorsal root ganglia were removed bilaterally and prepared for substance P and VIP extraction by radioimmunoassay technique. The control rabbits mean immunoreactive substance P was 14.06 pg/ml tissue, whereas the experimental or vibrated rabbits had a mean of 8.40 pg/ml (P less than 0.003). The control rabbits mean immunoreactive vasoactive intestinal peptide was 9.58 pg/ml whereas the experimental or vibrated rabbits had a mean of 20.9 pg/ml, P less than 0.07. Substance P is only one of several dorsal root ganglion neuropeptides that may play a role in nociceptor transmission. VIP is a neuropeptide that plays a role in reorganization of the nervous system following injury. The effects of low frequency vibration on dorsal root ganglion transmitters are essential to the understanding of vibration as a cause of back pain.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Strain in the lateral ligaments of the ankle.

Strain was measured in the normal anterior talofibular ligament (ATF) and the calcaneofibular ligament (CF) using Hall effect strain transducers in five cadaveric ankles. These measurements were made in both ligaments with the ankle in neutral position and with the foot moving from 10 degrees dorsiflexion to 40 degrees plantarflexion in an apparatus that permits physiologic motion. The ankle ligaments were then tested with the foot placed in six different positions that combined supination, pronation, external rotation, and internal rotation. In the neutral position, through a range of motion of 10 degrees dorsiflexion to 40 degrees plantarflexion, the anterior talofibular ligament underwent an increasing strain of 3.3%. No significant strain increase was found with internal rotation. The only significant difference from the strains at the neutral position was in external rotation, which decreased strain 1.9%. In all positions, increased strain occurred with increased plantarflexion. The calcaneofibular ligament was essentially isometric in the neutral position throughout the flexion arc. The calcaneofibular ligament strain was significantly increased by supination and external rotation. However, with increasing plantarflexion in these positions, the strain in the calcaneofibular ligament decreased. Therefore, plantarflexion has a relaxing effect on the calcaneofibular ligament. Thus, the anterior talofibular and calcaneofibular ligaments are synergistic, such that when one ligament is relaxed, the other is strained and vice versa.

Adult

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

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