Biomedical subjects
Publications and source records attributed to K Miller.
A compact, portable field instrument for measuring environmental gamma-ray exposure rates has been developed. Based on an 18 cm diameter pressurized ionization chamber, a temperature compensated MOFSET electrometer and a digital readout with selectable integration times, it is a considerable improvement over previously used larger and bulkier instruments of this type.
High school students who had at least one parent with hypertension (n = 22) were compared to schoolmates of the same age with a negative family history of hypertension in the parents (n = 21). We investigated in both groups the maximal rate of the ouabain-sensitive Na pump and the Na-K cotransport in nystatin-loaded cells and the Lii-Nao countertransport in lithium-loaded cells. The two groups were significantly different only in the sum of net Na transport mediated by the Na-K pump and Na-K cotransport. The mean diastolic blood pressure in the positive family history group was significantly higher. With control for blood pressure the difference in the maximal rate of Na transport was no longer significant; it remains uncertain if control for blood pressure represents "over-adjustment'. The finding of a higher maximal rate of Na transport in these adolescents who are at increased risk of future hypertension, yet currently well within the normal range, suggests that abnormal sodium metabolism may be a useful marker and appears early in the pathogenesis of this disease.
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We have investigated the ability of the gut-associated lymphoid tissues (GALT) to react against standard antigens presented via different routes of administration. When antigens were presented directly to GALT, either by an injection into the Peyer's patches or via a mechanically damaged lamina propria, a rapid and vigorous immune response ensued. This was manifested systemically as an antigen-specific humoral antibody response in the serum and locally as an antigen-specific immunoglobulin A response in the bile. These results indicate that GALT is capable of reacting to foreign materials penetrating the gut wall. Additional experiments demonstrated that the extended feeding of degraded iota carrageenan, a material known to produce non-specific mucosal inflammation, caused GALT to react to antigenic molecules present within the gastro-intestinal tract and enhanced both serum and biliary antibody responses against specific gut commensal microorganisms. The immunological significance of these observations is discussed.
Many workers severely exposed to inhaled particles have remained unaffected--what has protected them? Some workers have been affected despite mild exposure--what has rendered them vulnerable? There has been little progress in answering even the first question, and there can be no guarantee that factors rendering the lightly exposed vulnerable are the converse of those protecting the heavily exposed. An answer to the second question would be useful, say, for screening. But it requires study at the low end of the exposure scale, and there are many variables, probably intricately related, to be taken into account. A case/referent design might seem an obvious approach, but in its classical form it incurs essential and perhaps insurmountable difficulties. A longitudinal epidemiologic study would have to be very large, very complex, and very long in duration. Animal experiments also would have to be large and complex, probably embracing most of the animals' life span, but even so they could not take all relevant variables into account. It is recognized that the present paper has emphasized many difficulties and may thus appear negative in approach. Furthermore, although a compromise epidemiologic design is put forward, it is speculative.
The susceptibility of patients with cystic fibrosis to chronic, progressive bacterial pulmonary infections has not been adequately explained. We explored peripheral blood B-cell function in 21 cystic fibrosis patients and in normal controls. All patients were above 10 years of age, and chronically colonized with Pseudomonas aeruginosa. Spontaneous plaque-forming cells, which reflect B-cell differentiation into immunoglobulin-secreting cells in vivo, and plaque-forming cells formed after activation with pokeweed mitogen or staphylococci in vitro, were studied. Cystic fibrosis patients had significantly higher spontaneous plaque-forming cells than normal individuals. This difference was due to the increase of spontaneous plaque-forming cells than normal individuals. This difference was due to the increase of spontaneous plaque-forming cells in patients with less severe pulmonary disease, since patients with advanced pulmonary disease had numbers of circulating immunoglobulin-secreting cells, similar to normal individuals. Both groups of cystic-fibrosis patients have a significant impairment of B-cell differentiation in response to polyclonal activation in vitro. This functional abnormality could not be explained by the presence of increased numbers of adherent suppressor cells, or by the presence of increased suppression by T-lymphocytes. The implications of our data for the increased susceptibility to infection and for the development of antibody-mediated hypersensitivity reactions are discussed.
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The human glioma cell line D-54 MG and one of its single-cell-derived clones exhibit some properties of oligodendroglia, including surface antigens, enzymatic activity, and absence of markers for astrocytes. The glioma cells were further examined for glycolipids characteristic of oligodendroglia. The glioma cells had only about 2% of the total lipids as galactolipids while oligodendroglia have 10%. Incorporation studies showed only 25% of the incorporation of galactose into galactolipids as found in oligodendroglia. Sphingomyelin and phosphatidylinositol appeared to be increased. Several phospholipids exhibited high levels of incorporation of substrates, e.g., phosphatidylcholine and phosphatidylinositol. The ganglioside patterns were much less complex for the glioma cells. Thus, the glioma cells have greatly decreased amounts of glycolipids when compared to oligodendroglia. This finding is consistent with the theory that the loss of glycolipids on the cell surface may lead to the loss of regulation of contact inhibition.
To determine if there is a differential effect of hyperthermia on AKR murine leukemia and AKR normal bone marrow cells incubated in vitro, the fractional survival of leukemic and of normal cells with proliferative potential as a function of heating exposure was estimated by evaluating spleen colony formation. Normal bone marrow colony-forming units were assayed in lethally irradiated (750 centigrays) mice; leukemic colony-forming units were assayed in nonirradiated mice. Electron micrographic studies of leukemic cells treated with 41.8 degrees hyperthermia found that structural damage to the cell, i.e., changes in the Golgi apparatus, was associated with the lack of ability to form colonies. AKR leukemia cells were more sensitive than normal cells to hyperthermic killing at 41.8 degrees and at 42.5 degrees. This differential was found whether cells of each type were heated separately or when mixed together. This model system demonstrates an inherently greater sensitivity of neoplastic cells, as compared to normal syngeneic stem cells, to thermal killing. This finding may have relevance to autologous bone marrow transplantation in humans.
Examination of syngeneic tumor regressor sera prepared by immunization of mice with several different lymphomas revealed a common pattern of reactivity to proteins expressed in these tumors. Antibodies present in these sera immunoprecipitate a triplet of proteins of 115,000 mol wt (p115), 80,000 mol wt (p80), and 32,000 mol wt (p32) from many but not all T cell lymphomas of mice. P80, the predominant molecular species immunoprecipitated with these sera, is a nonglycosylated, phosphoprotein that does not appear to be expressed at the cell surface. Comparison of the tryptic peptides of p32 and p80 indicated that the peptides found in p32 are a subset of those found in p80. Comparison of the tryptic peptides of p80 with those of the p120 gag-fusion protein of Abelson murine leukemia virus demonstrated that p80 and p120 did not share tryptic peptides. Comparison of the partial proteolytic products generated by treatment of p80 molecules from different tumors with V8 protease did not reveal heterogeneity in p80 among tumors of different strains of mice. Direct labeling and competition blocking experiments with lysates from normal cells failed to provide evidence of p80 synthesis in normal thymus, spleen, or bone marrow. Thus, p80 is a biochemically identified tumor-related antigen of mouse lymphomas.
Biochemical studies from a patient with the late infantile form of metachromatic leukodystrophy are presented. Since the autopsy was performed soon after death, viable cells were isolated from brain. The purified cells had altered densities and unusual appearances. The cells when placed in culture were able to incorporate radiolabeled substrates into cerebrosides, indicating that some of the cells were of oligodendroglial origin. Myelin was isolated using several different methods, and the degree of abnormality appeared to be dependent upon the method of isolation. Nonetheless, MLD myelin, while still retaining its characteristic-morphology, had increased levels of sulfatides (two to four times that normally found). Other membrane subfractions were isolated that were not present in control tissue and that were more abnormal in composition than myelin. Finally, the glycoproteins in MLD tissue also appeared to be altered. There were losses in MLD myelin glycoproteins that bind to Concanavalin A (Con A) and additional prominent glycoproteins that bind to wheat germ agglutinin.
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Oligodendroglia were isolated from human multiple sclerosis (MS) brain obtained at autopsy. The cells were placed in culture and assessed for functions associated with normal oligodendroglia. The oligodendroglia from MS tissue were able to incorporate radiolabeled substrate into the lipids found in brain, including cerebrosides. They also produced whorls of membrane lamellae, adjacent to the cell soma, while in culture. In these respects the oligodendroglia from affected tissue were able to function normally.
Pharmacokinetic parameters of cefaclor were studied in eight patients after an oral dose of 250 mg. Serum samples were obtained before and on 19 occasions after oral administration. Cefaclor serum concentrations were determined by a new high-performance liquid chromatographic technique.
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Theophylline has recently shown to affect lymphocyte reactivity. In view of its widespread use in newborn intensive care units, the effects of both lymphocyte proliferation and immunoglobulin production at varied theophylline concentrations were measured. In 12 adults and 10 term infants lymphocyte proliferation, as assessed by a whole blood micromethod, was significantly decreased in vitro at 7.5 micrograms/ml. Immunoglobulin production in adults was decreased, by both a plaque forming cell assay and a radioimmunoassay in vitro at 12.5 micrograms/ml. Ten premature infants on theophylline, mean serum level 7.8 +/- 0.4 micrograms/ml, followed for 3-5 wk, showed a slight increase in lymphocyte proliferative responses to pokeweed mitogen. These data demonstrate no in vivo suppression of lymphocyte proliferation in theophylline-treated neonates at low theophylline levels.