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Biomedical subjects

D J Macey

Publications and source records attributed to D J Macey.

At least 55 records · Page 3Linked to original sources
PubMed1992

Calcium biomineralization in the radular teeth of the chiton, Acanthopleura hirtosa.

A method has been devised for isolating the calcium biomineral from the iron biominerals and organic components present in the major lateral teeth of the chiton Acanthopleura hirtosa. Fourier-transform infrared spectroscopy of the calcium biomineral indicated that it was an apatite material containing carbonate and fluoride ions. Carbonate was not found to be present as a separate phase. The apatite was further separated into low and high density fractions, both of which showed crystallinity intermediate between that of bovine tibia cortical bone and human tooth enamel, as indicated by powder X-ray diffraction analysis. The calcified region of the major lateral teeth was also studied in situ using transmission electron microscopy and electron diffraction analysis, revealing a close spatial relationship between the mineral apatite phase and underlying organic matrix. It is suggested that the architectural arrangement of apatite biomineral and fibrous organic constituents imparts specialized mechanical properties to the tooth making it ideally suited for the task of obtaining food from hard surfaces.

Animals↗
PubMed1991

Organ-specific crystalline structures of ferritin cores in beta-thalassemia/hemoglobin E.

The cores of ferritins isolated from different organs of human subjects with beta-thalassemia/hemoglobin E (beta-thal/HbE) disease have different size distributions and crystallinities depending on the source organ. These patients have not been treated by hypertransfusion regimen or iron chelation therapy. beta-Thal/HbE spleens and livers yield ferritin cores which are less crystalline than those isolated from normal spleens and livers, reflecting the more rapid deposition of iron in the diseased state. Ferritins isolated from the hearts and pancreases of beta-thal/HbE subjects were found to have larger, more crystalline cores than those from the beta-thal/HbE livers and spleens, possibly as a consequence of the role of the heart and pancreas as long-term iron deposition sites in this iron overload pathology.

Ferritins↗
PubMed1991

Quantitative imaging of mouse L-6 monoclonal antibody in breast cancer patients to develop a therapeutic strategy.

L-6, a mouse IgG2a anti-adenocarcinoma monoclonal antibody (MoAb) with favorable immunopathology and mouse biokinetics, was evaluated for cancer radioimmunotherapy by pharmacokinetic studies in 10 patients with breast cancer. The effect of escalating the preinfused protein dose was studied in two patients at each level, using 50, 100, 150, 200 and 400 mg of unlabeled L-6 prior to a 10 mCi imaging dose of 131I L-6. Quantitative imaging, and blood and urine clearances were obtained. After the 50 mg preinfusion, rapid blood clearance and lung extraction of the radiopharmaceutical occurred immediately post injection. Greater preload amounts of L-6 were associated with an increase in the intercept of the slow phase of the blood clearance from 17 to 22% injected dose (ID) with 50 mg to 70 to 80% ID with 400 mg (P less than 0.01). Lung uptake of the radiopharmaceutical immediately post injection decreased from 15 to 19% ID (50 mg) to 6 to 8% ID (400 mg). Tumors were visualized only after larger L-6 preloads, but in these patients small chest tumors contained 0.6-1.2% ID (0.1% ID/g maximum). This study suggests that L-6 reactive sites that are readily available in the lung can be saturated, so that a subsequent dose of I-131 L-6 is delivered to the tumor. This approach provides a new strategy for developing an effective method for radioimmunotherapy using a MoAb that has some cross-reactivity. Quantitative imaging contributed to detection of the cross-reactivity and the strategy for overcoming it.

Adenocarcinoma↗
PubMed1990

Beta-thalassaemia/haemoglobin E tissue ferritins. I: Purification and partial characterization of liver and spleen ferritins.

Ferritins from liver and spleen of both beta-thalassaemia/haemoglobin E (HbE) and non-thalassaemic patients were purified by heating a methanol-treated homogenate, followed by molecular exclusion chromatography. The concentrations of ferritins in the beta-thalassaemia/HbE liver and spleen were calculated as 3.8 and 2.0 mg/g wet tissue. The beta-thalassaemia/HbE ferritin iron/protein ratios were higher than those of normal ferritins. On PAGE, all ferritins gave a single major monomeric band with only very small differences in their mobility. Ferritins from thalassaemic patients also possessed bands corresponding to oligomers. On SDS/PAGE, all ferritins were resolved into two major subunits: H and L with L subunit predominating. While the isoferritin profiles of ferritins from beta-thalassaemia/HbE liver and spleen were similar to each other and to those of normal liver and spleen, some extra bands were present in the acidic region. The microstructure of these pathological ferritins appears to result, to a large degree, from the particular nature and amount of iron loading present.

Electrophoresis, Polyacrylamide Gel↗
PubMed1990

Beta-thalassaemia/haemoglobin E tissue ferritins. II: A comparison of heart and pancreas ferritins with those of liver and spleen.

Tissue ferritins from beta-thalassaemia/haemoglobin E heart and pancreas were characterized by native PAGE, SDS/PAGE and isoelectric focussing, and compared with those isolated from corresponding liver and spleen tissue. On PAGE, all ferritins consisted of a single band assigned to the protein monomer. Small differences in electrophoretic mobility were found between the bands. The ferritins were resolved by SDS/PAGE into two major subunits, H and L, corresponding to molecular masses of 22.5 kDa and 19 kDa, respectively. The L subunit was predominant in all cases. The isoferritin profiles of all tissue ferritins were remarkably similar, consisting of a complex pattern of bands which were appreciably more basic than those obtained for horse spleen ferritin. The subunit composition and isoferritin profiles of the four tissue ferritins almost certainly reflect the defense mechanism of the body in synthesizing in all four tissue types a more stable long-term iron-storage isoferritin in order to detoxify and store the excess iron present due to the pathological condition of beta-thalassaemia/HbE.

Electrophoresis, Polyacrylamide Gel↗
PubMed1990

Erythrocyte binding factors in the sera of the adult lamprey Geotria australis.

Adults of the Southern Hemisphere lamprey Geotria australis possess three major factors in their sera which bind to erythrocytes in vitro; in addition, an induced factor can also be demonstrated in the sera of animals immunized against human erythrocytes. These factors are a hemagglutinin, a hemolysin and a further binding factor together with a probable antibody. Furthermore, differences in agglutination patterns following immunization were noted between animals of different age groups. Old adults possessed a unique dilution pattern, containing a negative zone which occurred shortly after the initial dilutions, followed by a return to the normal agglutination pattern in the higher dilutions to a titer of 2(18). While the greatest agglutinating activity took place in sera taken from immunized animals, all animals possessed weak, low titer nonspecific direct agglutination together with a strong nonspecific binding activity which was revealed only by the use of an antiserum to lamprey plasma proteins. It is suggested that the interaction of these factors may account, in some measure, for the confusion concerning the nature and magnitude of the immune response in this phylogenetically important group of animals.

Age Factors↗
PubMed1989

Quantitative SPECT of uptake of monoclonal antibodies.

Absolute quantitation of the distribution of radiolabeled antibodies is important to the efficient conduct of research with these agents and their ultimate use for imaging and treatment, but is formidable because of the unrestricted nature of their distribution within the patient. Planar imaging methods have been developed and provide an adequate approximation of the distribution of radionuclide for many purposes, particularly when there is considerable specificity of targeting. This is not currently the case for antibodies and is unlikely in the future. Single photon emission computed tomography (SPECT) provides potential for greater accuracy because it reduces problems caused by superimposition of tissues and non-target contributions to target counts. SPECT measurement of radionuclide content requires: (1) accurate determination of camera sensitivity; (2) accurate determination of the number of counts in a defined region of interest; (3) correction for attenuation; (4) correction for scatter and septal penetration; (5) accurate measurement of the administered dose; (6) adequate statistics; and (7) accurate definition of tissue mass or volume. The major impediment to each of these requirements is scatter of many types. The magnitude of this problem can be diminished by improvements in tomographic camera design, computer algorithms, and methodological approaches.

Antibodies, Monoclonal↗
PubMed1988

Exceptional iron concentrations in larval lampreys (Geotria australis) and the activities of superoxide radical detoxifying enzymes.

This study aimed to elucidate the way in which larvae of the lamprey Geotria australis counteract the potential problems of the very high concentrations of non-haem iron they contain and thereby avoid the deleterious effects associated with iron overload in other vertebrates. Particular attention has been paid to ascertaining whether increasing concentrations of iron are accompanied by (i) change to a less readily available form of iron and (ii) an increase in the activity of those detoxifying enzymes responsible for minimizing the production of harmful hydroxyl radicals via the Haber-Weiss reaction. The mean concentrations of haemosiderin and ferritin in larval G. australis were each far higher in the nephric fold than in either the liver or intestine, but all these concentrations were much greater than those in rat liver. Since haemosiderin releases iron far more slowly than ferritin, the iron it contains is much less readily available to catalyse the Haber-Weiss reaction. It is thus relevant that (i) non-haem iron in the nephric fold occurred to a greater extent as large dense haemosiderin granules than as ferritin molecules and (ii) the proportion of iron in the form of haemosiderin rose with increasing concentration of total non-haem iron. A strong correlation was also recorded between the activity of superoxide dismutase in the nephric fold and the concentrations of total non-haem iron and its haemosiderin and ferritin components. This demonstrates that enzyme detoxification of O2.- rises with increasing amounts of iron. The exceptional iron concentrations in the nephric fold were not reflected by a greater measured activity of superoxide dismutase than that found in other tissues. However, the nephric fold was shown to contain an augmentation factor which is presumed to enhance the activity of this enzyme in vivo. The activity of catalase and glutathione peroxidase, which catalyse the breakdown of H2O2 to O2 and water, were each significantly correlated with the concentration of ferritin.

Animals↗
PubMed1988

Treatment of B cell malignancies with 131I Lym-1 monoclonal antibodies.

Lym-I is a murine IgG2a monoclonal antibody (MAb) that is B-cell specific but has greater avidity for malignant B cells when compared with normal B lymphocytes. It was originally produced by immunizing mice with nuclei of cultured cells from a patient with Burkitt's lymphoma. Ten patients with progressive refractory B-cell malignancies were treated with 131I-labelled Lym-I. Treatment with 131I Lym-I produced complete or partial remissions in 4 patients. Toxicity did not occur or was mild in most patients. The only significant complications included two instances of fistula secondary to necrotic lymphoma and one instance of hypotension. Human antimouse antibodies occurred in only 2 patients after multiple injections of Lym-I antibody. This experience was in contrast to treatment of B-cell malignancies with unconjugated Lym-I alone. Unconjugated Lym-I also caused no significant toxicity but was less effective than 131I Lym-I.

Antibodies, Monoclonal↗
PubMed1988

Comparison of three boundary detection methods for SPECT using Compton scattered photons.

Three simple methods of defining the boundary of a transverse section in single photon emission computed tomography (SPECT) were compared using Compton scattered photons from a small 99mTc source located either inside or outside a water-filled cylinder of 22 cm diameter. Scattered events were acquired with 360-degree rotation of the gamma camera and transverse section images were reconstructed using a filtered backprojection method. The boundary of section images obtained with three different geometric arrangements of the source and the camera were compared. The 90-degree Compton scatter method, using a source external to the cylinder and at 90 degrees to the front of the detector, was found to give the best boundary definition. Similarly, detection of scattered events using a radionuclide source placed outside a human body was capable of providing good boundary information for the large stack of contiguous section images produced by a rotating SPECT camera. Calculations confirmed the profound influence of boundary errors on SPECT quantitations.

Models, Structural↗
PubMed1988

Uptake of indium-111-labeled monoclonal antibody ZME-018 as a function of tumor size in a patient with melanoma.

The accumulation of an Indium-111-labeled monoclonal antibody (MoAb), ZME-018, in melanoma tumors in a patient was determined by sequential, quantitative gamma camera imaging. The amount and concentration of In-111 in each tumor changed in a characteristic pattern with time, reaching a peak at day 3 followed by a steady clearance. The concentration of In-111 in the tumor and the ratios of tumor to whole-body or blood decreased as the size of the tumor increased. These results were interpreted to indicate that the fraction of active, perfused tumor decreased as the melanoma lesions increased in size. The maximum number of MoAb molecules bound per melanoma cell was calculated to be abut 35,000. The implications of these observations for radioimmunoimaging and therapy are significant.

Antibodies, Monoclonal↗
PubMed1986

Changes in the amount of nonhaem iron in the plasma, whole body, and selected organs during the postlarval life of the lamprey Geotria australis.

The concentration of plasma nonhaem iron and the concentration and weight of all nonhaem iron in the whole body and selected organs, together with its partitioning into ferritin and haemosiderin iron, have been measured during the metamorphosis and upstream spawning migration of the Southern Hemisphere lamprey Geotria australis. Some nonhaem iron was lost from the animal during metamorphosis. However, the concentration and weight of nonhaem iron in the liver rose sharply at this time, following its release from important storage sites in adipose tissue and the degradation of larval haemoglobins. The nephric fold of larval and metamorphosing stages contained over 40% of all nonhaem iron in the body at the commencement of metamorphosis. This was predominantly in the form of haemosiderin. While the rise in liver iron during the transition from larva to adult primarily reflected an increase in the weight of ferritin iron, the amount of iron stored as haemosiderin rose conspicuously towards the end of metamorphosis. The rise in ferritin iron in the liver was accompanied by a decrease in ferritin iron in the plasma, which implies that changes in the liver during metamorphosis result in a greater filtering of circulating ferritin. Such a process would account for the very much lower plasma nonhaem iron concentrations which characterise later adult stages. The weight of nonhaem iron increased markedly in the liver and adult opisthonephros and in the whole animal during the nontrophic upstream spawning migration. This was primarily due to a marked rise in ferritin which in turn could be related to the degradation of adult haemoglobins.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1986

Multicompartmental analysis of the kinetics of radioiodinated monoclonal antibody in patients with cancer.

A conceptual biologic model was developed and used to analyze the behavior of 123I-Lym-1 monoclonal antibody against African human B cell lymphoma in patients with B cell lymphoma. Originally, the observed data could not be simulated with parameters for homologous immunoglobulins reported in the literature because of a major processor that was capable of distinguishing this murine immunoglobulin from the patient's own immunoglobulins. With a nonlinear parametric model, the data observed in patients could be fitted to the model. The nonlinear parameter determined the transfer of antibody from the intravascular to a processor compartment, primarily the liver. This transfer was a function of the number of free receptors in the processor. Model simulated curves for the time course of concentration of antibody in the blood for different amounts of injected antibody revealed that blood clearance of radiolabeled antibody was profoundly decreased by increased amount of injected antibody. This model provides an explanation for the observations that tumor imaging is improved with injection of larger amounts of antibody, and a basis for modifying the pharmacokinetic behavior of an antibody in order to optimize radioimmunodiagnosis and radioimmunotherapy.

Antibodies, Monoclonal↗
PubMed1986

Comparison of low- and medium-energy collimators for SPECT imaging with iodine-123-labeled antibodies.

The planar and single photon emission computed tomography (SPECT) imaging performance of two low-energy and one medium-energy collimators has been compared for 123I(p,5n). Septal penetration in the low-energy collimators affected the planar uniformity and sensitivity and made the usual uniformity correction methods inappropriate. SPECT uniformity and resolution were also distorted by these artifacts induced in the planar images obtained with the low-energy collimators. The planar and SPECT images of a SPECT phantom contradicted the spatial resolution measurements made with a line source in air. The medium-energy collimator is recommended for imaging 123I(p,5n)-labeled antibodies in patients, particularly when quantitation is required.

Antibodies↗
PubMed1985

Requirements for a treatment planning system for radioimmunotherapy.

Cancer-seeking antibodies carrying radionuclides can, in theory, be very powerful agents for the radiotherapy of cancer. However, as with all radiotherapy, the undesired dose to critical normal organs is the limiting factor that determines success or failure. The distribution of radiation dose in cancer and noncancer tissue is highly dependent on choices the therapist can make: choices of the antigens to be targeted, choices of the antibodies or antibody fragments to be used, choices of radionuclides, of amounts, of timing, and other electives. New technologies, especially of monoclonal antibody production, make the options myriad. Optimization of this therapy depends on a foreknowledge of the radiation dose distributions to be expected. The necessary data can be acquired by established tracer techniques, in individual patients, for particular treatment selections. These tracer techniques can now be implemented by advanced equipment for quantitative, tomographic radionuclide imaging and strengthened by dynamic modeling of the physiological parameters which govern radionuclide distribution, and hence radiation dose distribution.

Animals↗