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Biomedical subjects

M C Walker

Publications and source records attributed to M C Walker.

At least 109 records · Page 6Linked to original sources
PubMed1986

Studies of the ferroxidase activity of native and chemically modified xanthine oxidoreductase.

The O2-utilizing (type O, oxidase) form of xanthine oxidoreductase is primarily responsible for its ferroxidase activity. This form of xanthine oxidoreductase has 1000 times the ferroxidase activity of the serum ferroxidase caeruloplasmin. It has the ability to catalyse the oxidative incorporation of iron into transferrin at very low Fe2+ and O2 concentrations. Furthermore, the pH optimum of the ferroxidase activity of the enzyme is compatible with the conditions of pH that normally exist in the intestinal mucosa, where it has been proposed that xanthine oxidoreductase may facilitate the absorption of ionic iron. Modification of the molybdenum (Mb) centres of the enzyme in vitro by treatment with cyanide, methanol or allopurinol completely abolishes its ferroxidase activity. The feeding of dietary tungsten to rats, which prevents the incorporation of molybdenum into newly synthesized intestinal xanthine oxidoreductase, results in the progressive loss of the ferroxidase activity of intestinal-mucosa homogenates. Removal of the flavin centres from the enzyme also results in the complete loss of ferroxidase activity; however, the ferroxidase activity of the flavin-free form of the enzyme can be restored with artificial electron acceptors that interact with the molybdenum or non-haem iron centres. The presence of superoxide dismutase or catalase in the assay system results in little inhibition of the ferroxidase activity of xanthine oxidoreductase.

Animals↗
PubMed1986

Intravesical chemotherapy: in vitro studies on the relationship between dose and cytotoxicity.

The relative importance of two variables, drug concentration and period of exposure, in relation to the therapeutic potential of intravesical chemotherapy was examined in an experimental system. A human bladder cancer cell line was exposed to a range of concentrations of the four drugs commonly used to treat superficial bladder cancer (adriamycin, epodyl, mitomycin-c, thiotepa) for periods of 30, 60 and 120 min. An exponential relationship was observed between clonogenic cell kill and both drug concentration and period of exposure. Thus, under the experimental conditions employed, cytotoxicity is proportional to dose (i.e. concentration X period of exposure). These two variables are of equal importance in relation to tumor cell kill, indicating that maximum therapeutic benefit may be obtained by using the highest concentration achievable for as long as the patient can retain the instillate, bearing in mind the potential increase in toxicity to the patient and the cost.

Antineoplastic Agents↗
PubMed1986

Hybrid resistance to BALB/c plasmacytomas: F1 hybrid anti-MPC-11 immunological responses correlated with resistance to tumor challenge.

BALB/cJ X C57BL/10Sn F1 (hereafter called B10F1) hybrids resist challenge with the BALB/c plasmacytoma, MPC-11, by a radiation-sensitive, silica-insensitive mechanism, whereas BALB/cJ X BALB.B F1 (hereafter called BALB.BF1) hybrids are as susceptible to MPC-11 as are homozygous BALB/c mice themselves. To investigate the mechanism of resistance, we have compared anti-MPC-11 immune responses by these F1 hybrids both before and at various times after tumor challenge. Resistance is not determined by natural killer cell reactivity inasmuch as neither hybrid harbors splenic natural killer cells with lytic activity directed against MPC-11. Nor is it determined by antibody-dependent cell-mediated cytotoxicity since neither hybrid produces an appropriate anti-MPC-11 antibody. Spleen cells and lymph node cells from both hybrids are capable of generating high levels of anti-MPC-11 cytotoxic T-lymphocyte activity in both primary and secondary mixed-lymphocyte tumor cell cultures. Such cytotoxic T-lymphocytes protect susceptible hybrids from tumor growth in Winn assays. The susceptible but not the resistant hybrids lose the ability to generate high levels of cytotoxic T-lymphocytes activity in spleen mixed lymphocyte tumor cell cultures by 28 days, and in lymph node mixed-lymphocyte tumor cell cultures by 14 days postchallenge. The reduction in spleen cell reactivity is due to suppression mainly by adherent cells and can be abrogated by pretreatment of the susceptible hybrids with a low dose of Cytoxan 2 days before challenge. This pretreatment does not, however, protect the mice. They develop tumor at the same rate and die at the same time as do controls. Both the late appearance of suppression and the lack of effect on survival of its ablation suggest it to be a concomitant of tumor growth rather than its cause. Resistance to tumor growth in this model system may reflect an enhanced ability of the resistant hybrid to deliver effector cells to the site of tumor implantation.

Animals↗
PubMed1985

Comparison of patterns of hybrid resistance to the BALB/c plasmacytomas LPC-1 and MPC-11.

Patterns of genetic control of hybrid resistance to the BALB/c plasmacytoma LPC-1 were studied for comparison with those to MPC-11, a plasmacytoma investigated previously. The overall patterns of hybrid resistance to the two tumors were similar, i.e., hybrids between BALB/c and BALB congenic resistant (CR) strains, A and A CR strains, SJL and DBA/2 were as susceptible to LPC-1 as BALB/c mice themselves, whereas hybrids between BALB/c and AKR, C57BL/Ks, DBA/1, C57BL/6 (B6), C57BL/10 (B10) and B10 CR strains were resistant to LPC-1 as previously shown with MPC-11. Heterozygosity within the H-2 complex alone was insufficient for resistance to either tumor. Among hybrids between BALB/c and the B10 CR strains, however, the presence of certain H-2 haplotypes influenced the degree of resistance seen and this H-2 effect was different for the two tumors. A sex effect on resistance to LPC-1, but not to MPC-11, was seen among F1 hybrids between BALB/c and DBA/1 although not in any other F1 hybrids. Among ((B10 X BALB/c)F1 X BALB/c) and (BALB/c X (B10 X BALB/c)F1) and ((BALB/c X B10)F1 X BALB/c) and ((BALB/c X B10)F1 X BALB/c) backcross mice, however, significantly more males than females were resistant to LPC-1 and the results of this study are compatible with the idea that in F1 hybrids between BALB/c and B10, resistance to LPC-1 is controlled by two dominant autosomal genes, one of which is sex-limited and neither of which is linked to H-2. In contrast, hybrid resistance to MPC-11 in this cross is controlled by a single gene. Cross-protection experiments indicated that the two tumors share at least one tumor-associated transplantation antigen.

Animals↗
PubMed1985

A new erythrocytic antigen of C57BL/10 (B10) mice.

A new antigen, detectable on murine erythrocytes by hemagglutination assay with a (BALB/cCrl X SWR/J)F1 anti-B10.D2n/Sn alloantiserum, is described. Among the inbred and congenic mouse strains tested for reactivity with the antiserum, only the immunizing strain, B10.D2, and its congenic resistant partner, C57BL/10 (B10), reacted. Three other C57 strains, C57BL/6J, C57BL/6By, and C57L, were negative for the antigen. F1 hybrids between B10 and BALB/c, an antigen-negative strain, were positive for the antigen indicating that its expression is dominant. Typing of 39 (BALB/c X (BALB/c X B10)F1) and 62 [BALB/c X B10)F1 X BALB/c) backcross mice revealed that a single gene controls expression of the antigen. The gene is autosomal and not linked to H-2, Ly-4, or the c (albino) or b coat color genes.

Animals↗
PubMed1984

Artificial ventilation for cardiopulmonary resuscitation.

The ability of 100 members of the nursing staff to administer artificial ventilation was tested on a manikin. Six techniques of artificial ventilation were used. A minimum minute volume of 6 L was chosen as the criterion for adequate ventilation. Eighty-eight per cent of nurses "passed" using mouth-to-mouth ventilation, 66% "passed" using mouth-to-face-mask, 55% "passed" using the RM-1 injector system, 52% "passed" using the Mistviva injector system, while very low "pass" rates of 25% and 15% were obtained with the Air-Viva and Mapleson B circuits, respectively. It was concluded that mouth-to-mouth technique was the best form of ventilatory support provided by the nursing staff tested in this trial. In general, the use of mask systems should be restricted to highly trained staff members who have demonstrated continuing proficiency.

Australia↗
PubMed1984

The metabolism of intravenously infused neurotensin in man and its chromatographic characterization in human plasma.

The metabolism of iv infused neurotensin (NT) was studied and its disappearance half-time compared with that of infused N-terminal octapeptide of NT 1-8 in six normal subjects by RIA with antisera directed against the C- and N-terminal regions of the NT molecule. The disappearance half-time of NT in circulating plasma was 1.4 min measured with the C-terminal antibody and 6.0 min measured with the N-terminal antibody. The disappearance half-time of NT 1-8 was 30 min measured with the N-terminal antibody. Gel filtration and high pressure liquid chromatographic analysis indicated that a substantial amount of immunoreactive NT in the plasma of subjects infused with synthetic NT was eluted at the NT 1-8 position and a lesser amount of plasma NT-like immunoreactivity was eluted with synthetic NT. These findings suggest that NT is readily metabolized in the circulation to NT 1-8. A significant rise in the mean plasma concentration of pancreatic polypeptide was produced by NT, but not by NT 1-8, infused at 2.4 pmol kg-1 min-1. No changes in the mean plasma concentrations of insulin, glucose, or cholesterol were demonstrated during either infusion. The present study suggests that the rapid degradation of NT in man to its N-terminal metabolite may be one of the mechanisms for its bioinactivation in plasma.

Adult↗
PubMed1983

Asplenia and polysplenia malformation complexes explained by abnormal embryonic body curvature.

Asplenia and polysplenia malformation complexes characteristically have severe cardiovascular defects and visceral heterotaxy. We examined the hypothesis that the conditions may arise from an altered timing of development of embryonic body curvature: delayed in asplenia, accelerated in polysplenia. The morphologic features of the 25 patients with asplenia and 15 with polysplenia autopsied at The Johns Hopkins Hospital were determined. The time of appearance of various morphologic features and the evolution of body curvature was studied in 351 staged serially sectioned human embryos of The Carnegie Embryological Collection. All asplenia patients had severe atrioventricular canal malformations. Bilateral trilobed lungs were found in 12 patients. The polysplenia patients had severe interatrial septal defects in 10 patients; but ventricular septal defects in only six. Bilateral bilobed lungs were seen in five patients. Comparison of the time of appearance of anatomic structures in normal embryos with the observed malformations suggest that asplenia and polysplenia complexes originate in stages 13 to 15. The observations are consistent with the concept that the malformations in asplenia and polysplenia can be explained by minor alterations in the sequence of development of embryonic body curvature relative to organ maturation.

Adult↗
PubMed1983

Genetic control of corticosteroid side-chain isomerase activity in the mouse.

The corticosteroid side-chain isomerases of mammalian liver catalyze the interconversion of the ketol and aldol side chains. In the mouse, isomerase was low in C57BL/6 (B6) mice (130 pmol/mg protein . 2 h) and high in BALB/c (C) mice (230 pmol/mg protein . 2 h). From analysis of hybrids between B6 and C and of backcrosses of these hybrids to B6, it was concluded that isomerase levels are controlled by a single autosomal gene dominant for high activity. The distribution of high and low isomerase levels in a series of CXB/By recombinant inbred strains of mice was consistent with linkage of the isomerase gene to H-2. Congenic BALB.B mice (H-2b haplotype from C57BL/10) had low isomerase activities corresponding to C57BL/10, not the high activity of the background strain BALB/c(H-2d). Similarly, BN10.D2 congenic mice (H-2d haplotype from the DBA/2 strain) had high activity characteristic of DBA/2. In the (C X B6)F1, (C X BALB.B)F1 and (B10 X B10.D2)F1 hybrids, all of which are H-2d/H-2d heterozygotes, isomerase activity was high. The association of isomerase levels with H-2 type was further confirmed in mice of the following backcrosses: (C X BALB.B)F1 X BALB.B, (C X B6)F1 X B6 and (B10 X B10.D2)F1 X B10. H-2b/H-2b homozygous segregants had consistently low activity and H-2b/H-2d heterozygous segregants had consistently high activity. It was concluded that the level of corticosteroid side-chain isomerase activity in mouse liver is controlled by a gene(s) in the region of the H-2 locus on chromosome 17.

Animals↗
PubMed1981

Purification and characterization of the intestinal promoter of iron(3+)-transferrin formation.

The nonceruloplasmin enzyme located in the intestinal mucosa which promotes the incorporation of iron into transferrin has been resolved into a small, heat-stable component and a heat-labile protein component. The small, heat-stable component was purified from the high-speed supernatant of intestinal mucosal homogenates by ion-exchange chromatography and gel filtration and identified as xanthine. The heat labile protein component was purified from the high-speed supernatant of intestinal mucosal homogenates by heat treatment, gel filtration, and ion-exchange chromatography. The physical, spectral, and kinetic properties of the heat-labile protein component strongly suggest that it is xanthine oxidase. By promotion of the oxidation and incorporation of iron into transferrin, intestinal xanthine oxidase could perform a similar function in iron absorption as ceruloplasmin serves in the mobilization of iron from liver stores.

Allopurinol↗
PubMed1981

Simultaneous determination of niacinamide, pyridoxine, riboflavin, and thiamine in multivitamin products by high-pressure liquid chromatography.

A high-pressure liquid chromatographic assay was developed for the determination of four water-soluble vitamins: niacinamide, pyridoxine, thiamine, and riboflavin. The four vitamins are assayed simultaneously in multivitamin products not containing minerals. Thiamine currently is not quantitated in formulations containing minerals because it is not stable under the extraction conditions. The method was applied to the analysis of at least 12 different multivitamin products, including various formulations of sterile products, fluids, compressed tablets, and coated, compressed tablets. The method is stability indicating and is applicable to single-tablet assays.

Chromatography, High Pressure Liquid↗
PubMed1979

Hybrid resistance to BALB/c plasmacytomas. II. Radiation sensitivity and silica insensitivity of resistance to MPC-11.

Resistance to the BALB/c plasmacytoma MPC-11 by F1 hybrids between BALB/c and four C57BL/10 congenic resistant strains was abrogated or reduced by 450 rads total body irradiation but was unaffected by intravenous injection of 3 to 4 mg of silica. The results are consistent with the idea that hybrid resistance to MPC-11 depends on an active immune response and is different from Hh-1 controlled hybrid resistance.

Animals↗
PubMed1979

Hybrid resistance to BALB/c plasmacytomas. I. Resistance to MPC-11 controlled by a locus not linked to H-2.

Genetic control of hybrid resistance to the BALB/c plasmacytoma MPC-11 was investigated. The results indicate that a single dominant autosomal gene or gene complex, which segregates independently of H-2 and the coat color c and b-loci, controls resistance to this tumor. This gene has the same strain distribution pattern in the CXB Bailey recombinant inbred strains as three unlinked genes, H-2, Ly-4, and Ea-4. It is possible, therefore, that it could be linked to either of the latter two loci. Strains that carry a positive allele for resistance are C57BL/10 and all of its congenic resistant partners tested, C57BL/6, C57L, C57BL/Ks, AKR, and DBA/1. BALB/c and its congenic resistant partners are presumed to carry a negative allele of the gene for resistance to MPC-11. Strains such as SJL, DBA/2, and A and its congenic resistant partners, which form susceptible hybrids with BALB/c, could carry either the negative allele of the gene for resistance, like BALB/c, or could carry both a positive allele of the gene and some other gene conferring susceptibility on the hybrids. Heterozygosity within the H-2 complex increases resistance only in the presence of this non-H-2 linked gene for resistance, and the effect maps to the left of the H-2D region.

Animals↗
PubMed1978

Effect of hydrostatic tensile stress on the growth of Escherichia coli and Bacillus cereus.

The specific growth rates of Escherichia coli and Bacillus cereus were measured for growth media in a flask, a lens-plate arrangement simulating an isolated capillary space, and a lens-plate arrangement under hydrostatic tensile stress. The specific growth rates of the bacteria were the same for the flask and lens-plate arrangement without hydrostatic tensile stress, but were enhanced when the growth media were subjected to hydrostatic tensile stress. The enhanced specific growth rates reached steady values at a tensile stress of 40 pascals. The effect was observed up to tensile stresses of around 100 pascals. The maximum increase in specific growth rate was 25% for E. coli and 22% for B. cereus.

Bacillus cereus↗
PubMed1978

Genetic control of resistance to tumors.

Hybrid resistance to a BALB/c plasmacytoma, MPC-11, has been investigated. The results indicate that heterozygosity within the H-2 complex is neither necessary nor sufficient for resistance to be observed. However, in the presence of a single gene or gene complex which segregates independently of H-2, differential effects of various H-2 haplotypes can be seen. Resistance is radiation-sensitive and silica-insensitive and probably depends on active immune responses. The data also suggest that production by a hybrid of endogenous viral antigens with certain type-specific determinants shared with viral antigens expressed on the tumor may interfere with resistance. The mechanism for this is not understood but might involve tolerance, suppression, or enhancing antibody.

Animals↗