Biomedical subjects
Publications and source records attributed to B Pope.
A system of stereotactic radiosurgery using a linear accelerator is described and the experience with a variety of neurosurgical lesions including gliomas, acoustic neurinomas and arteriovenous malformations is recorded. The system is simple, inexpensive and effective and can be used with any CT scanner and linear accelerator.
Pig plasma gelsolin has been prepared by a revised method involving poly(ethylene glycol) precipitation, chromatography on CM-cellulose and affinity chromatography on actin-Sepharose. Pig platelet gelsolin has been prepared by chromatography on DEAE-cellulose and actin-Sepharose. Partial chemical and proteolytic cleavage shows that the two proteins are closely related in their fragmentation patterns. The amino acid sequences are identical at the N-terminus of the platelet protein, but the plasma protein has an additional nine residues on the N-terminal side of the common sequence. Calcium binding studies show that the plasma protein has similar calcium binding properties to both macrophage and platelet gelsolins.
The interaction of pig plasma gelsolin with F-actin has been studied by a sedimentation assay using 125I-gelsolin in a Beckman Airfuge. Over 90% of the gelsolin bound to F-actin in 0.1 mM CaCl2 in experiments using 24 microM actin and 2-10 nM 125I-gelsolin, but only 40-50% bound in 1 mM EGTA. Addition of more F-actin to the EGTA supernatant does not sediment this gelsolin. Demonstration of this partial calcium sensitivity depends critically on the use of F-actin that has been prepared in the absence of calcium ions. F-actin prepared from G-actin in calcium or pretreated with calcium, binds 125I-gelsolin more completely in EGTA. This suggests that gelsolin activity is influenced by transient exposure of actin to calcium. Further evidence for partial calcium sensitivity in the interactions between gelsolin and F-actin has been obtained by other methods, including viscometry and electron microscopy. The gelsolin present in the EGTA supernatant is complexed to G-actin, predominantly as binary complexes. Very low concentrations of these complexes reduce the viscosity of F-actin in calcium but not in EGTA. Whether this effect is due to severing activity, or capping with consequent depolymerization to establish the new critical concentration, is uncertain. The results suggest the presence of two types of gelsolin, one that requires micromolar concentrations of calcium for binding to F-actin and one that does not. Both bind to G-actin. Partial separation has been achieved using actin-Sepharose. Pig plasma gelsolin is heterogeneous on isoelectric focussing gels in urea, but the two types of gelsolin separated on actin-Sepharose do not correspond to specific isoelectric species.
The transmembrane topography of the rat hepatocyte ectoenzyme 5'-nucleotidase was studied by the use of glycoprotein labelling and limited-proteolysis techniques. Comparison, by one-dimensional peptide mapping, of enzyme iodinated from outside the cell with that iodinated in the solubilized state showed that no additional iodination sites were revealed on solubilization. Incubation of newly synthesized enzyme in a microsomal membrane fraction with proteinase showed that the entire molecule of 5'-nucleotidase was protected from proteolysis. These data suggest that little, if any, of the 5'-nucleotidase molecule is present on the cytoplasmic side of the plasma membrane. No evidence was found for a previously proposed interaction between 5'-nucleotidase and actin, although the ability of preparations of 5'-nucleotidase to prevent inhibition of deoxyribonuclease I by actin was explained by minute traces of ATPase activity. Comparison of peptide maps of enzyme labelled by iodination or by methods specific for carbohydrate showed that in both cases predominantly one section of the molecule was labelled. It is proposed that the enzyme is a short-stalked integral membrane protein without a cytoplasmic domain in which about one-third of the molecule forms the accessible molecular surface.
Computerized digital image analysis of the optic nerve head was performed using a simultaneous stereoscopic video camera system to provide rapid, quantitative measurements of optic nerve head topography. Determination of the variability of the measurements is required to estimate the magnitude of optic nerve change over time that can be reliably detected. Total variability, operator variability, and interoperator variability were studied. Total variability was assessed by analyzing ten sets of video recordings made in each of seven eyes of seven normal subjects, and in seven eyes of seven patients with glaucoma. The median coefficients of variation for measurements of total variability in glaucoma patients were as follows: vertical disc measurement, 1.4%; horizontal disc measurement, 2.1%; disc area, 1.9%; vertical cup/disc, 3.9%; horizontal cup/disc, 3.3%; disc rim area, 7.5%; and volume, 7.6%. Operator and interoperator variabilities were considerably smaller in magnitude.
Four groups of three C57/BL6J mice were each given a single i.p. injection of Cyclosporine A (CYA) 3 mg/kg, containing 3H-CYA with 10 microCi activity. The groups were sacrificed after 5 minutes and at 6, 12 and 24 hours after dosing, respectively. They were immediately flushed with PBS to clear the organs of blood, and the CYA content of blood, kidney, liver, brain, thymus, spleen, heart, lung, muscle and femur were measured by scintillation counting. Hemoglobin concentration in each tissue was negligible. Tissue uptake was expressed as the ratio of activity per gm tissue/activity per ml blood. Organs susceptible to CYA toxicity, e.g., brain, kidney and liver demonstrated retention of CYA relative to blood, as did thymus and spleen. Resistant organs, i.e., heart, lung and muscle did not. The pattern of CYA distribution and clearance corresponded with the known susceptibility of organs to CYA toxicity. CYA kinetics could therefore contribute to its toxicity by means of increased retention and/or accumulation in susceptible organs.
There have been many reports of cases in which chronic increases in the numbers of natural killer (NK) cells have been reported. Whether this is reactive or neoplastic in nature has been debated. We report the first case of an aggressive NK cell leukemia in an adult with establishment of an NK cell line. A 70-year-old man had two spontaneous episodes of jejunal perforation and one month later developed a severe febrile illness with moderate splenomegaly. Hemoglobin was 13.1 g/L, and WBC count was 1.8 X 10(9)/L with 2% large granular lymphocytes (LGLs). Platelet count was 143 X 10(9)/L; prothrombin time (PT) and partial thromboplastin time (PTT) were normal. Bone marrow was infiltrated with 25% to 30% LGLs; serum lysozyme was normal. Serum LDH was initially 1,191 U/L and rose to 6,408 (normal 240 to 525 U/L). Ten days later, the WBC count increased to 99.9 X 10(9)/L with 70% LGL cells; the PT and PTT increased, and the platelet count dropped. No bacterial or viral cause of fever was identified. The cells from peripheral blood were LGLs that stained positively for acid phosphatase. All of the LGLs reacted with a monoclonal antibody reactive with NK cells (LEU-11b). Functionally, the patient's peripheral blood mononuclear cells (PBMs) demonstrated 100 times more lytic activity against K562 tumor cell lines than did normal PBMs. The patient's PBMs were propagated in vitro. The cultured cells showed the morphological, cytochemical, immunological, and functional characteristics of NK cells. In addition, partial trisomy involving chromosome 1 q with duplication in regions of q21 through q31 was observed in all metaphases analyzed. The extra chromosome 1q with duplication in regions q21 through q31 was translocated to the p-terminal of chromosome 5. One percent to 5% of normal PBMs comprise NK cells; in most cases, leukemias arise from normal phenotypic counterparts. This case demonstrated that aggressive NK cell leukemia may occur in adults. In addition, the chromosomal abnormalities suggest that this is not a reactive process but a malignancy.
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Myosin isoenzymes, highly enriched in either alkali 1 or alkali 2 light chains have been prepared by light chain exchange in 4.7 M ammonium chloride, under conditions where there is minimal loss of ATPase activity. While the actin-activated ATPase measurements were complicated by a biphasic dependence on actin concentration, the two myosin isoenzymes behaved in a similar manner; at a variety of ionic strength conditions their maximum rates of ATP hydrolysis were nearly identical. Furthermore, under conditions where their Km values could be reliably determined, their apparent affinities for actin in the presence of ATP did not differ greatly. These results suggest that the presence of a particular alkali light chain does not influence the maximum rate of ATP turnover by actomyosin under ionic strength conditions approximating physiological.
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Specific B cell responses to influenza viruses were induced by in vitro stimulation of spleen cells from normal or influenza-immune mice with inactivated influenza virus. Both primary and secondary responses to A/Pt Chalmers/73 (A/Pt Ch/73) and A/New Jersey/76 (A/NJ/76) viruses were detected in a hemolytic plaque assay, with peak numbers of specific plaque-forming cells (PFC) present after 4 days of incubation. Depletion of macrophages from BALB/c spleen cell suspensions by treatment with either carrageenan or carbonyl iron markedly reduced the primary and secondary B cell responses to influenza virus. The responses could be restored by reconstitution with either BALB/c or CBA/J macrophages. Specificity of the antibody response was demonstrated in cross-reaction experiments with A/Pt Ch/73 and A/NJ/76 viruses. Evidence of recall to A/NJ/76 virus was, however, found in A/NJ/76-immune spleen cells stimulated in vitro with A/Pt Ch/73 virus. Greatest in vitro stimulation of A/Pt Ch/73-immune spleen cells was produced with inactivated whole A/Pt Ch/73 virus preparations; specific responses were low or absent after stimulation with preparations of partially disrupted virus vaccine, a mixture of purified hemagglutinin (HA) and neuraminidase antigens or soluble hemagglutinin containing similar amounts of viral HA antigen. This lack of response to A/Pt Ch/73 HA could not be overcome with A/NJ/76 whole virus together with purified A/Pt Ch/73 HA.
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