Biomedical subjects
J Keller
Publications and source records attributed to J Keller.
The relative roles of interleukins 1, 2, and 3 in the regulation of T cell differentiation.
The initial description and purification of IL 3 was based on its potential relevance in early T cell differentiation. Although the data do not provide conclusive evidence for a role of IL 3 in T cell differentiation, a number of observations provide some indications that a relationship exists. The most intriguing aspects are concerned with the distribution and regulation of expression of 20 alpha SDH. This particular marker is interesting since it may allow studies of aspects of T cell differentiation that have not been possible with more conventional approaches. The available data are consistent with the hypothesis that in the bone marrow there exists a stem cell that in response to IL 3 is induced to differentiate including the induction of expression of 20 alpha SDH and Thy 1+. Phenotypically this induced cell is similar to a medullary thymocyte, although the cells derived in vitro clearly do not have the functional characteristics of medullary thymocytes. It can be rationalized that a bone marrow-induced prothymocyte may require the thymic microenvironment for continued maturation. Irrespective of this, it now becomes necessary to further explore the possibilities by extending the approaches used to define and study early bone marrow-localized pre-T cell populations as well as continuing to define the necessary components of the thymus in the differentiation pathway for T cells. In these areas of research the experience and systems derived from studies of long-term bone marrow cultures will be of considerable value. In addition to the proposed role that IL 3 plays in early T cell differentiation, it is apparent that the stem cell that is induced to differentiate may have considerably more potentials than the T cell lineage. The ability of IL 3 to induce the differentiation of 20 alpha SDH-positive mastlike cells in vitro is the most demonstrable functional phenotype. The absolute requirement of Il 3 throughout the differentiation of such cells indicates that in vivo, where IL 3 is generally not detectable, the frequency with which such progeny are obtained may be quite low and restricted to unique immunological situations in which high levels of IL 3 are produced. In addition, it appears likely that IL 3 induces the differentiation of a cell that in the presence of erythropoietin can be induced to differentiate along an erythroid pathway. Last, IL 3 may induce the differentiation of promyeloblasts that can differentiate in the presence of CSF-2 [unpublished data].(ABSTRACT TRUNCATED AT 400 WORDS)
Rehabilitation--the care controversy.
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[Erythropoietic protoporphyria].
A 21-year-old patient was observed with oedematous-purpura-like skin changes since earliest childhood occurring in areas with short-term exposure to sunlight. The history suggested erythropoetic protoporphyria and the diagnosis was established by demonstration of fluorocytes in peripheral blood and subsequent porphyrin analysis. Whereas chronic persistent skin changes characteristic of erythropoetic protoporphyria were largely absent, histologic and immunohistologic findings were typical. The patient had been considered a "neurotic outsider" for many years because of his aversion to light which was considered abnormal.
Immunofluorescence studies in progressive systemic sclerosis (scleroderma) and mixed connective tissue disease.
Immunofluorescence (IF) investigations of the skin were performed in thirty patients with progressive systemic sclerosis (scleroderma) and eight patients with mixed connective tissue disease (MCTD). The results show that speckled epidermal nuclear immunoglobulin deposition occurs not only in MCTD but also in true scleroderma. Granular IgM deposition at the dermo-epidermal junction of light-exposed skin was detected in both groups of patients, but six of eight MCTD patients also showed a granular IgM band in non-exposed skin. Antinuclear antibodies (ANA) were demonstrated in the sera of 96% and 100% of patients with scleroderma and MCTD respectively. The pattern of nuclear IF staining in scleroderma included dense fine speckles, large coarse speckles, threads, nucleolar and centromere staining. In MCTD, by contrast, the ANA staining pattern consisted of threads. The significance of ANA titres and immunological specificities for the in vivo reaction of serum ANA with epidermal nuclear antigens is discussed.
Biologic properties of homogeneous interleukin 3. I. Demonstration of WEHI-3 growth factor activity, mast cell growth factor activity, p cell-stimulating factor activity, colony-stimulating factor activity, and histamine-producing cell-stimulating factor activity.
Interleukin 3 (IL 3) was initially defined as a factor in conditioned media from concanavalin A-stimulated lymphocytes (Con A CM) that induces the enzyme 20-alpha-hydroxysteroid dehydrogenase (20 alpha SDH) in cultures of nu/nu splenic lymphocytes. To determine the spectrum of additional "biologic" activities, IL 3 was purified to homogeneity and its properties were assessed. The protein preparation was judged to be homogeneous IL 3 by the following criteria: 1) elution of a peak of IL 3 with a constant specific activity in the last step of purification, 2) presence of a single protein by SDS-PAGE analysis, 3) receptor-binding activity against IL 3-dependent cell lines, 4) a specific activity of congruent to 0.2 ng/ml required for 50% of maximal biologic activity, and 5) the presence of a single amino terminal sequence. With the use of this preparation of IL 3, the dose-response curves for 20 alpha SDH induction were identical or similar to the dose-response curves for the activities of 1) WEHI-3 growth factor, 2) mast cell growth factor, 3) P cell-stimulating factor, and 4) histamine-producing cell-stimulating factor. In addition, homogeneous IL 3 had colony-stimulating factor activity, although only approximately 2% of the total CSF activity found in Con A CM was associated with IL 3. The major peak of CSF activity could be resolved from IL 3 by DEAE column chromatography and lacked many of the biologic activities associated with IL 3.
[Postoperative separation of Christansen's hip prosthesis].
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[Spontaneous bilateral rupture of the Achilles tendon].
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The immune response to C-type viruses and its potential role in leukemogenesis.
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Interleukin 3: possible roles in the regulation of lymphocyte differentiation and growth.
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Phenotypic characteristics of cell lines requiring interleukin 3 for growth.
A number of cell lines have been derived from bone marrow cultures in the presence of WEHI-3 conditioned media (CM) that continue to require WEHI-3 CM for growth in vitro. Because the WEHI-3 cell line has been shown to constitutively produce a lymphokine (IL 3) that induces the expression of 20 alpha-hydroxysteroid dehydrogenase (20 alpha SDH) in cultures of splenic lymphocytes from athymic mice, we examined whether these cell lines were dependent upon IL 3 for growth. The results demonstrate that the factor required for growth of these cell lines copurifies with IL 3 activity on G-100, DEAE cellulose, and CM cellulose column chromatography as well as in preparative isoelectric focusing and on hydrophobic supports in reverse phase high pressure liquid chromatography. The biologic activity of peak fractions in each case was similar in both types of assays. These results strongly suggest that the WEHI-3 CM-dependent cell lines are dependent on IL 3 for growth in vitro. All the cell lines have readily detectable levels of 20 alpha SDH but have differing cell surface phenotypes. The C3HSFFV line is devoid of conventional lymphoid cell surface markers with the exception of Lyt-1, whereas the FDC-P1 expresses Thy-1, Ly-5, and H-11. Other cell lines have intermediate phenotypes.
Procedures for the purification of interleukin 3 to homogeneity.
A procedure is described for the routine purification of IL 3 to homogeneity from WEHI-3-conditioned media. The techniques employed include ammonium sulfate fractionation, DEAE-cellulose, hydroxylapatite, and G-75 Sephadex column chromatography. The last step in purification involves chromatography on C18 hydrophobic supports in RP-HPLC systems, which results in the coelution of a protein peak and IL 3 activity. This purification sequence results in approximately a 1,000,000-fold purification from the initial starting material with yields of 5 to 10% of the initial activity. typically, 150 liters of conditioned media yields 2 to 10 micrograms of IL 3. The purified material was homogeneous by SDS-PAGE analysis and had an apparent m.w. of 28,000. Purified IL 3 had a specific activity of approximately 0.05 ng/unit of activity. Additional criteria used to establish the relationship of the 28,000-dalton protein to IL 3 include the ability of an antiserum against IL 3 to concomitantly immunoprecipitate the iodinated protein and to inhibit its biologic activity as well as the ability of the iodinated protein to bind specifically to cell lines known to require IL 3 for growth.
High pressure liquid chromatographic determination of mono- and disaccharides in presweetened cereals: Collaborative study.
A collaborative study was conducted using a modified AOAC method (sugars in chocolate) for the determination of fructose, glucose, sucrose, and maltose in presweetened cereals by high pressure liquid chromatography (HPLC). Eight samples consisting of 6 products were analyzed in duplicate by the HPLC method and the AOAC Lane-Eynon method. The AOAC method was modified to use water-alcohol (1 + 1) and Sep-Pak C18 cartridges for sample cleanup. The HPLC results indicate precision comparable to the lane-Eynon method and the chocolate method. The modified HPLC method has been adopted official first action.
[Electro-oculography and the glaucomatous eye (author's transl)].
A study was conducted using precise electro-oculographic measurements and taking into account not only Arden's "ratio" but also the absolute values in 14 cases of open angle and 3 cases of closed angle glaucoma. Results showed that in cases of open angle glaucoma there was an overall increase in base line values which was more pronounced for the minimal value (dark through); in the case of closed angle glaucoma there was an increase in the maximal value (light rise). After surgery there is an overall increase of the base line value in the operated eye.
[Evoked potentials and structured stimulations].
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A sclerocorneal electrode for the study of the characteristics of primate vision under condition of space flight.
We describe here a physiologically nonirritating sclerocorneal lens electrode of special design for making reproducible, low noise electroretinographic recordings on frogs and the rhesus monkey. The apparatus should be particularly useful in studying the effect of space flight factors on these responses in man.
Studies of blood pressure in Tecumseh, Michigan. I. Blood pressure in young people and its relationship to personal and familial characteristics and complications of pregnancy in mothers.
Relationships between blood pressures (BPs) of young people and a number of personal, parental and familial characteristics have been assessed in the population of Tecumseh, Michigan. Systolic and fifth phase diastolic BPs were measured in 4500 persons under 20 years of age at the time of their first examination. Body size, fatness and heart rates of the subjects themselves were significantly related to their age- and sex-adjusted BP scores. The parents' BP scores were also correlated with those of the young subjects, and scores were significantly higher in those whose mothers had had high BP or toxemia in pregnancy of a stillbirth. A weak association between BP and socioeconomic circumstances was suggested by the slightly higher mean BP scores found in sons and daughters of men in blue collar jobs and of men and women with the least education. BP levels were not associated with birth order, sibship size or birth weight nor with the numbers of pregnancies, live births or abortions experienced by the mothers of young subjects. In a stepwise multiple regression, the most important determinants of BP were weight/height ratios of the subjects themselves and BP levels of their parents; a small additional effect of complications of pregnancy in the mother was detectable in the offspring 0--19 years laters.
[Prognostic aspects of acute hepatitis].
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