PubMed Health⌕ Search

Biomedical subjects

C S Johnson

Publications and source records attributed to C S Johnson.

At least 19 recordsLinked to original sources
PubMed1992

Retinal vessel autoregulation in sickle cell patients.

We tested retinal vessel autoregulation in 16 sickle cell patients and 6 controls by computer-assisted measurements of constriction of the superior and inferior temporal veins and arteries after pure oxygen breathing. Compared to the controls and corrected for age, we found a decrease of vasoconstriction in three of the four vessels measured in the sickle cell group, which was statistically significant only for the superior temporal artery (P 0.009). The number of patients was too small to allow a separate analysis of possible contributory factors within the sickle cell group, such as sickle cell hemoglobin subtype and extent of retinal ischemia. Our findings indicate a factor not yet well known in the pathophysiology of sickle cell disease: an abnormality of local microvascular control.

Adult↗
PubMed1992

Induction of permanent regression of Friend virus (FV) leukemia by adoptive transfer of T helper and not T cytotoxic cells.

Friend virus (FV) induces a progressive erythroleukemia that can be made to permanently regress by the transfer of in vitro cultured virus-specific T cells (CTL/RFB) without any other adjunctive treatment. To determine the role of T cells in regression, CTL/RFB were enriched for specific T-cell subsets by treatment with monoclonal anti-Lyt2.2 or anti-L3T4 antibody and complement (C'). Pre-treatment of CTL/RFB with anti-Lyt2 antibody and C' did not affect permanent regression incidence, while CTL/RFB depleted of L3T4+ cells induced temporary regressions with all mice recurring. The number of splenic Lyt2+ (CD8+ equivalent) cells was constant irrespective of the leukemic status of the animals. However, the number of L3T4+ cells (CD4+ equivalent) in leukemic mice was three-fold lower than that of normal mice with regressed mice demonstrating a 30% increase in the number of L3T4+ cells compared to normals. Spleen cells from leukemic animals were also unable to produce IL-2 in response to mitogen stimulation. These results indicate that L3T4+ cells are involved in regression of erythroleukemia.

Animals↗
PubMed1992

Modulation of chemotherapy antineoplastic agents with biologic agents: enhancement of antitumor activities by interleukin-1.

Cytokines or biologic response modifiers in combination with traditional chemotherapeutic agents can be used as therapeutics in patients with cancer. Biologic response modifiers, which are involved in the control and regulation of a wide variety of physiologic activities, have previously been used primarily to enhance or boost host immunologic function. Although immune modulatory therapeutic approaches are yet to be fully realized, biologic response modifiers have also been considered in combination with cytotoxic drugs for their effects on hematopoietic progenitor cells, tumor cells directly, and microvascular endothelial cells. Interleukin-1 is a multifunctional cytokine that not only activates the immune system but also plays a central role in regulating hematopoiesis, has potent effects on vascular function, and has shown significant antitumor activity alone or in combination with various chemotherapeutic agents. As a result, interleukin-1 is an excellent candidate for combination with conventional antineoplastic drugs toward the design of innovative therapeutic approaches to malignancy. This review examines the studies using preclinical animal tumor models as well as the recent phase I clinical trials and includes an overview of their potential for further application.

Antineoplastic Agents↗
PubMed1992

Stabilization of perflubron emulsions with egg yolk phospholipid.

Egg Yolk Phospholipid(EYP) has been used extensively as the primary surfactant in parenteral fat emulsions for many years. The simplicity, functionality and physiologic tolerance of EYP has contributed greatly to its success in the intravenous emulsion arena. The mechanism of stabilization in triglyceride emulsions is well understood; however, this is not the case with perfluorocarbon emulsions. Interfacial models, as well as emulsion stability studies, have been conducted utilizing EYP of varied composition in order to derive a structure/function relationship. Our studies indicate that minor components, total unsaturation, acyl chain length and presence of charged species have significant impact on the functional properties of EYP and the subsequent stability of the emulsion product. These findings contribute to our ability to design and manipulate natural surfactants with superior properties for use in medical applications of perfluorocarbon emulsions.

Blood Substitutes↗
PubMed1992

Differential effect in vitro of tumor necrosis factor-alpha (TNF) on normal and virus-infected erythroid progenitors from Friend virus (FVA)-infected mice.

In vivo administration of tumor necrosis factor-alpha (TNF) suppresses both normal and Friend virus (FVA)-infected erythroid progenitor cells (CFU-E). To examine the mechanism of erythroid suppression by TNF, we examined TNF's direct effect on normal and virus-infected cells in vitro. Productively infected fibroblast cell lines, fresh acute virus-infected spleen cells, and virus-infected CFU-E were sensitive, whereas uninfected CFU-E were resistant to TNF cytotoxicity in vitro. When FVA-infected erythroblasts were depleted from the spleen cell population in vitro with antivirus antibodies, TNF suppression of the remaining (uninfected) cells was abrogated. In contrast, both normal and virus-infected macrophage progenitor cells and immature erythroid progenitor cells were equally sensitive to TNF cytotoxicity in vitro. Normal erythroblasts had significantly fewer TNF receptors than FVA-infected erythroblasts, which also were morphologically less mature. These results suggest that TNF can differentially suppress late-stage virus-infected erythroid progenitors in vitro.

Animals↗
PubMed1991

Potentiation of mitomycin C and porfiromycin antitumor activity in solid tumor models by recombinant human interleukin 1 alpha.

The time- and dose-dependent effects of recombinant human interleukin 1 alpha (IL-1 alpha) on the antitumor activity of mitomycin C (MMC) and porfiromycin (PORF) were studied in RIF-1 and Panc02 solid tumor model systems. IL-1 alpha produced dose-dependent sensitization of clonogenic RIF-1 tumor cells to MMC in vivo. IL-1 alpha chemosensitization was highly schedule dependent, and the most efficacious schedules produced dose-modifying factors of 3.6 and 5.1 for MMC and PORF, respectively. More than additive clonogenic cell kill after IL-1 alpha-chemotherapy combinations reflected increased cellular sensitivity to MMC and PORF. The combinations also produced marked decreases in the yield of viable tumor cells, suggesting that the bioreductive drugs may have also potentiated the microvascular injury and ischemia produced by IL-1 alpha. Dexamethasone inhibited and ketoconazole, an inhibitor of corticosterone biosynthesis, enhanced IL-1 alpha-mediated chemosensitization in these models. IL-1 alpha mediated chemosensitization to MMC, and PORF was also demonstrated by tumor growth inhibition in the RIF-1 model and increased survival of mice in the spontaneously metastasizing Panc02 system. Chemosensitization of bone marrow spleen colony-forming units was not seen. IL-1 alpha (1000 units/ml) had no effect on MMC and PORF cytotoxicity in RIF-1 and PORF cell lines in vitro. The results indicate that the tumor-specific IL-1 alpha-induced pathophysiologies can sensitize solid tumors to agents which are preferentially activated, retained, and cytotoxic to cells under hypoxic conditions. Our results suggest that strategies combining bioreductively activated hypoxic cell cytotoxins and biological agents might offer efficacious alternatives or adjuvants to conventional combination approaches.

Animals↗
PubMed1991

Negative regulators of in vivo erythropoiesis: interaction of IL-1 alpha and TNF-alpha and the lack of a strict requirement for T or NK cells for their activity.

The macrophage-derived cytokines interleukin 1 alpha (IL-1 alpha) and tumor necrosis factor-alpha (TNF-alpha) have significant effects on hematopoiesis in vitro and in vivo. Studies in our laboratory have demonstrated that, in vivo, IL-1 alpha and TNF-alpha suppress late stage erythropoiesis while stimulating the macrophage-granulocyte lineage. In the present studies, we have examined the mechanisms of these effects. Normal mice were treated with a single dose of either recombinant murine IL-1 alpha or TNF-alpha (1.25 x 10(6) or 10(5) U/mouse i.p., respectively) with or without pretreatment of the animals with monoclonal anti-murine TNF-alpha antibody at a dose that has been shown to be capable of abrogating endogenous TNF activity induced by lipopolysaccharide (LPS). After 5 days, effects on late-stage erythropoiesis and macrophage formation were measured by determining the number of their progenitors, erythroid colony-forming units (CFU-E) and macrophage colony-forming units (CFU-M), in the spleen. Anti-TNF-alpha antibody treatment significantly abrogated CFU-E suppression by IL-1 alpha but had no effect on the IL-1 alpha-induced stimulation of CFU-M. IL-1 alpha and TNF-alpha suppressed CFU-E in vivo and stimulated CFU-M in the spleens of T-cell- and natural killer (NK)-cell-deficient mice. Neither cytokine suppressed CFU-E colony formation in vitro. These results demonstrate that IL-1 alpha-induced suppression of CFU-E is mediated through induction of TNF-alpha, IL-1 alpha stimulation of CFU-M was independent of TNF-alpha, and the in vivo hematopoietic effects of these cytokines do not strictly require intact T- and NK-cell function for activity.

Animals↗
PubMed1979

Release of soluble "blocking" and "suppressor" factors from normal lymphocytes treated with RNA from spleens of tumour-bearing mice.

RNA extracted from the spleens of tumour-bearing (TLRNA) and tumour-immune (ILRNA) mice was shown to transfer to normal lymphocytes (NL) the ability to produce factors that blocked specific tumour-cell cytotoxicity and mediated specific antibody-dependent cell cytotoxicity (ADCC). Aliquots of normal C3H mouse lymphocytes were treated with TLRNA or ILRNA and cultured in vitro in the absence of tumour antigen. Supernatants were collected at 24h intervals and tested in a microcytotoxicity assay for blocking and ADCC activities. Factors that inhibited tumour destruction by specifically sensitized lymphocytes at the level of both the tumour cells and effector cells were demonstrable in culture supernatants of NL pretreated with TLRNA (50 or 100 microgram/4 X 10(6) cells) but not ILRNA. However, treatment of NL with either RNA resulted in the production factors that mediated tumour-specific ADCC. Cytotoxicity testing and absorption studies of the tumour cell and a control cell (LM) indicated that factors mediating ADCC and blocking at the target-cell level were specific for the tumour. Suppressor activity at the effector-cell level was not absorbed by tumour cells and represents a separate and distinct mechanism of immunosuppression. These data indicate that RNA faithfully transfers "suppressive" as well as "positive" types of immune responses that have been reported previously for lymphocytes obtained directly from tumour-bearing and tumour-immune animals.

Animals↗
PubMed1979

Acute lymphocytic leukemia manifesting as splenic rupture.

Pathologic rupture of the spleen is a rare phenomenon in acute lymphocytic leukemia, and its mechanism is unknown. This complication has been seen almost exclusively in men, and at ages much older than those of the majority of patients who have this leukemia; these unusual features are also unexplained. A case of acute lymphoctyic leukemia with pathologic rupture of the spleen in which the pathologic findings suggest that the splenic rupture was due to infiltration and destruction of the splenic capsule by leukemic cells is reported.

Adult↗
PubMed1979

The radiologic significance of the left pulmonary ligament. Experience with 26 patients.

Pathologic processes confined to or by the left pulmonary ligament present a confusing radiographic appearance. Such processes may simulate pleural scarring, parenchymal scarring, or even left lower lobe collapse. Radiologic awareness of this structure is limited because in the normal state, it is not visualized on either posteroanterior or lateral chest x-ray films. The absence of secondary signs of left lower lobe collapse, together with a process which may extend above the level of the left hilum, is valuable in confirming that such a triangular density seen behind the left cardiac border is disease in or confined by the pulmonary ligament, rather than left lower lobe collapse.

Adult↗
PubMed1979

Intravenous iron-dextran in the treatment of iron deficient anemia.

Administration of oral ferrous salts is the preferred method of treatment for anemia due to iron deficiency. However, in certain clinical situations, the response to oral therapy may be suboptimal. Parenteral iron therapy is effective in these instances and may produce a faster response than the oral route.Of 30 patients treated by total dose intravenous infusion of iron-dextran, a prompt reticulocytosis occurred in all patients except one case associated with systemic lupus erythematosus. Hematologic improvement in this case followed remission of the systemic lupus erythematosus. Hematologic response was complete in 18 patients in five to nine weeks, but could not be evaluated in 11 cases because of recurrent bleeding. There were two adverse reactions: generalized pruritus after injection in one patient, and superficial thrombophlebitis at the injection site of another.The response to therapy in iron deficient anemia is dependent on bone marrow capacity, the severity of the anemia, and the availability of iron. Response was fastest in those who had been severely anemic for prolonged periods of time. Total dose infusion with iron-dextran is a safe and effective treatment for iron deficient anemia in selected cases. Initial response appears to be faster than that on oral therapy with the exception of those with a mild degree of anemia.

Adult↗
PubMed1978

Racial patterns in pernicious anemia. Early age at onset and increased frequency of intrinsic-factor antibody in black women.

Pernicious anemia affects primarily elderly northern Europeans, but may affect others more often than previously thought. Therefore, we analyzed the data from 156 documented cases: there were 73 patients of "European" origin, 52 black patients and 31 Latin-American patients. The mean age (+/- 1 S.D.) at presentation among black women, 53 +/- 16 years, was lower than that of all the others (P less than 0.001 in most comparisons), and seven of the 33 black women were less than 40 years old. In addition, 23 of the 24 black women tested had circulating antibody to intrinsic factor. A similar though less striking antibody prevalence (85 per cent) and age pattern (60 +/- 13 years) in Latin-American women did not reach statistical significance. No other group exceeded the usual 55 to 70 per cent prevalence of antibody. These finding suggest a different form of or a different response to the disease in black women and perhaps in Latin-American women.

Adult↗
PubMed1978

Bilirubin-protein interactions monitored by difference spectroscopy.

Difference spectroscopy is used to monitor bilirubin-protein interactions, to assess the residual binding capacity of proteins for bilirubin. A change in the difference spectra monitored at 482 nm is directly proportional to bound bilirubin up to a molar ratio of bilirubin to albumin of approximately 1; increasing bilirubin beyond the 1:1 molar ratio does not further change the difference spectra. After excess free bilirubin is added, the change in the difference spectrum is proportional to the residual binding capacity of the serum for bilirubin. The risk of kernicterus among neonates may be assessed by monitoring the residual bilirubin binding capacity of serum. This report summarizes our research effort leading to an assay method which requires only 40 microliter of serum and can be completed in less than 10 min.

Adult↗