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Biomedical subjects

F L Johnson

Publications and source records attributed to F L Johnson.

At least 55 records · Page 3Linked to original sources
PubMed1989

Metabolic behavior of hepatic VLDL and plasma LDL apoB-100 in African green monkeys.

Recently, evidence has accumulated suggesting that significant amounts of plasma low density lipoproteins (LDL) may be derived by direct production. These plasma very low density lipoprotein (VLDL)-independent sources include the production and secretion of LDL-like particles directly by the liver, and/or a small pool of nascent precursor particles that are converted rapidly to LDL. The current studies were designed to test the hypothesis that hepatic VLDL represent a rapidly turning over precursor pool to plasma LDL in African green monkeys. Livers from African green monkeys were perfused with serum-free medium containing [3H]leucine or 3H-labeled amino acids for 4-6 hr. Hepatic [3H]VLDL and autologous plasma 125I-labeled LDL were injected simultaneously into recipient animals and density gradient ultracentrifugation and gel filtration were used to characterize the distribution of 3H and 125I radioactivity at selected times after injection. These studies show that 4 to 66% of the injected dose of hepatic VLDL [3H]apoB-100 was metabolized extremely rapidly into particles that resembled the recipient's plasma LDL by size and density. Based on the kinetic model developed to describe the metabolic behavior of hepatic VLDL [3H]apoB-100, the estimated maximal pool size of hepatic VLDL apoB-100 in these animals was very small (0.042 and 0.112 mg) and represented, at best, approximately 10% of the average plasma VLDL apoB-100 mass found in cholesterol-fed African green monkeys. In addition, the radiolabeled hepatic LDL appear to be metabolized similarly to plasma LDL. That is, the rapid conversion of hepatic VLDL as well as the direct production of hepatic particles within the LDL density range appear to contribute to plasma LDL. Metabolic heterogeneity was also seen within the LDL class. The more buoyant subfraction (LDL1) had a higher turnover rate than the more dense subfraction (LDL2) and hepatic VLDL-derived [3H]LDL1 had a slower final rate of plasma disappearance than the plasma-derived 125I-labeled LDL1 in most animals. The results from these studies suggest that a small pool of hepatic VLDL can be converted very rapidly to plasma LDL and may contribute significantly to the large plasma pool of LDL seen in cholesterol-fed African green monkeys. This pathway may be analogous to the pathway in some human subjects in which a portion of human plasma VLDL is converted rapidly into LDL without passing through a delipidation cascade, often referred to as direct LDL production.

Animals↗
PubMed1988

[The effect of Campath-1 on T- and NK-cells].

An assay system capable of detecting 0.03% residual T cells is described. This test system was used to evaluate bone marrow which was treated with Campath-1 and human complement (HC'). All T cell-depleted samples tested were found to be free of OKT3-positive T cells (less than 0.03%). The assay described provides a highly sensitive method for the detection of residual T cells and can be used as an alternative to limiting dilution assays. The results presented here confirm that treatment of donor bone marrow with Campath-1 and HC' provides a highly effective means of removing T cells and thus should be effective in GVHD prevention. However, although Campath-1 effectively depletes T- and B cells, it unexpectedly failed to eliminate cells that display NK function.

Antibodies, Monoclonal↗
PubMed1988

Bone marrow transplantation for the treatment of acute nonlymphoblastic leukemia in children aged less than 2 years.

Eleven children with acute nonlymphoblastic leukemia in first remission who were less than 2 years of age at diagnosis were treated with 120 mg/kg of cyclophosphamide, 12-Gy fractionated total-body irradiation, and marrow transplantation. Seven patients remain in complete remission from 3.5 to 13.8 years posttransplant, four for more than 6.75 years. The immediate posttransplant course was relatively uncomplicated in surviving patients. No child developed severe graft-v-host disease. The major long-term side effect has been a slowing in growth. Although the prognosis for such children with conventional chemotherapy remains poor, intensive cytotoxic therapy and marrow transplantation offers an alternative therapy with a chance for cure.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Nascent lipoproteins from recirculating and nonrecirculating liver perfusions and from the hepatic Golgi apparatus of African green monkeys.

Perfusate apoB-100-containing lipoproteins from the isolated, perfused livers of African green monkeys consist of significant amounts of d greater than 1.006 g/ml particles in addition to very low density lipoproteins (VLDL). Distinguishing characteristics of these perfusate lipoproteins are the relative abundance of surface lipids and deficiency of core lipids. The present studies were performed to determine the likelihood that the d greater than 1.006 g/ml perfusate lipoproteins are secretion products instead of products of post-secretory modification (e.g., lipolysis) of secreted VLDL. [14C]Leucine from the perfusate became incorporated into the apoB of each of the perfusate lipoprotein classes to a similar extent in both recirculating and nonrecirculating perfusions. When endogenously radiolabeled perfusate VLDL from one liver was recirculated through a second liver, only about 15% of the radiolabeled protein appeared in the d greater than 1.006 g/ml fraction. The particle morphology and the cholesterol and apoB distribution between VLDL and d greater than 1.006 g/ml fractions were similar in recirculating and nonrecirculating perfusions. A Golgi apparatus-rich fraction was isolated from the homogenates of fresh liver samples and the isolated Golgi VLDL and d greater than 1.006 g/ml lipoproteins exhibited morphologic evidence of extra surface material analogous to that seen in perfusate. Taken together, these data support the possibility that significant amounts of d greater than 1.006 g/ml lipoproteins, many with surface-rich properties, are nascent, secretory products of the primate liver. The low level of lecithin:cholesterol acyltransferase (LCAT) in this perfusion system appears to permit detection of these secretion products and it is significant to note that the perfusate lipoprotein profile, which is unlike that of normal plasma, is similar to that of LCAT-deficient patients.

Animals↗
PubMed1987

Childhood monosomy 7 syndrome: clinical and in vitro studies.

The clinical and cell growth characteristics of 11 children with monosomy 7 presenting as preleukemia (eight cases) or acute nonlymphoblastic leukemia (three cases) were studied. Anemia was common to all patients, with nine showing leukocytosis, seven thrombocytopenia, and one thrombocytosis. There was a striking predominance of males (M/F ratio, 10:1) and a young median age (3 years). Preleukemia evolved to acute nonlymphoblastic leukemia in five patients and to myelofibrosis in one. In vitro studies of bone marrow progenitor cells cultured in leukocyte feeder-stimulated agar revealed abnormal cell proliferative patterns, most often an increased number of small clusters, for all 11 subjects. The cells of some preleukemic patients showed increased growth even in the absence of an exogenous source of colony-stimulating factor, suggesting autonomous growth or possibly autocrine stimulation. Combination chemotherapy or bone marrow transplantation failed to induce complete remission in the seven patients who were treated. Our findings in these 11 cases confirm the poor prognosis of monosomy 7 presenting as preleukemia in children. The in vitro studies suggest an association between altered cell growth in vitro and clinical evolution to frank leukemia.

Acute Disease↗
PubMed1986

Life satisfaction of the elderly American Indian.

This study examined the life satisfaction of 58 elderly American Indians and its relationship to selected external and internal environmental factors. Elderly Indians were 51-85 years of age and resided on two midwestern reservations. Data were collected through use of the Life Satisfaction Index Z-scale (LSI-Z), the Oars Multi-dimensional Functional Assessment Questionnaire (OARS) and a semi-structured interview schedule. Findings indicated that life satisfaction tended to be high. Six internal environmental variables explained 40% of the variance in life satisfaction scores. A higher correlation was found between self-perception of life satisfaction and mental health than objective ratings on these two variables. This study suggests that variables associated with the internal environment may be useful as indicators of life satisfaction in elderly reservation American Indians and that subjective measures of life satisfaction may be more predictive of mental health than objective measures.

Aged↗
PubMed1986

High density lipoprotein accumulation in perfusates of isolated livers of African green monkeys. Effects of saturated versus polyunsaturated dietary fat.

To determine whether altered hepatic secretion of HDL is part of the mechanism by which polyunsaturated fat lowers plasma HDL concentration, we have studied HDL secretion in the isolated perfused livers of African green monkeys fed an atherogenic diet containing either safflower oil as the polyunsaturated fat or butter as the saturated fat. During recirculating perfusion with a lipoprotein-free medium, livers from safflower oil-fed animals produced 21% less HDL mass on the average than those from butter-fed animals. Newly secreted hepatic HDL were characterized after their isolation and subfractionation by a combination of agarose column chromatography and density gradient ultracentrifugation. In both diet groups the HDL were heterogeneous in size, morphology, and composition and consisted of discoidal particles ranging in diameter from greater than 200 A to as little as 50 A. Large, discoidal particles that were rich in apoE and apoA-I were separated from small particles that were poor in apoE but rich in apoA-I. All hepatic HDL subfractions contained only small amounts of cholesteryl ester and triglyceride. The hepatic particles resembled in composition and structure the large variety of HDL particles found in the plasma of patients with the familial deficiency of lecithin:cholesterol acyltransferase. Accordingly, perfusate LCAT activity was measured and found to be 2% or less than that in monkey plasma. We conclude that the perfused monkey liver produces a variety of nascent HDL that are relatively unmodified by the post-secretory metabolic events which normally occur in blood plasma in vivo, and that livers of polyunsaturated fat-fed monkeys secrete fewer plasma HDL precursor particles than do those of saturated fat-fed monkeys.

Animals↗
PubMed1986

Lecithin:cholesterol acyltransferase-induced modifications of liver perfusate discoidal high density lipoproteins from African green monkeys.

The role of lecithin:cholesterol acyltransferase (LCAT) in the formation of plasma high density lipoproteins (HDL) was studied in a series of in vitro incubations in which perfusates from isolated African green monkey livers were incubated at 37 degrees C with partially purified LCAT for between 1 and 13 hr. The HDL particles isolated from monkey liver perfusate stored at 4 degrees C and not exposed to added LCAT contained apoA-I and apoE, were deficient in neutral lipids, and were observed by electron microscopy as discoidal particles. Particle sizes, measured as Stokes' diameters by gradient gel electrophoresis (GGE), ranged between 7.8 nm and 15.0 nm. The properties of perfusate HDL were unchanged following incubation at 37 degrees C in the presence of an LCAT inhibitor. However, HDL subfractions derived from incubations at 37 degrees C with active LCAT contained apoA-I as the major apoprotein, appeared round by electron microscopy, and possessed chemical compositions similar to plasma HDL. The HDL isolated from perfusate incubations at 37 degrees C with low amounts of LCAT had a particle size and chemical composition similar to plasma HDL3a. In three of four perfusates incubated with higher levels of LCAT activity, the HDL products consisted of two distinct HDL subpopulations when examined by GGE. The major subpopulation was similar in size and composition to plasma HDL2a, while the minor subpopulation demonstrated the characteristics of plasma HDL2b. The data indicate that the discoidal HDL particles secreted by perfused monkey livers can serve as precursors to three of the major HDL subpopulations observed in plasma.

Animals↗
PubMed1985

Fusion of low density lipoproteins with cholesterol ester-phospholipid microemulsions. Prevention of particle fusion by apolipoprotein A-I.

Little is known about the mechanism and control of lipoprotein particle fusion, although apoproteins are presumed to be important in maintenance of particle structure. This study characterizes the interaction of apo-B-containing low density lipoproteins (LDL) with cholesterol ester microemulsions (CEME) in the presence and absence of apo-A-I to determine if a role for these apoproteins in particle integrity could be ascertained. CEME are an apoprotein-free analog of LDL formed by sonication of radiolabeled phospholipid (surface) and cholesterol ester (core). Incubation of CEME with LDL followed by precipitation of LDL with MnCl2 resulted in coprecipitation of CEME with LDL that was time-, temperature-, and concentration-, but not pH (pH 6-9)-, dependent and occurred over a wide range of CEME and LDL particle compositions. Particles from the incubation were larger than the unincubated particles and intermediate in density and electrophoretic mobility between the starting LDL and CEME. Differential scanning calorimetry experiments suggested that CEME surface and core lipids had mixed with those of LDL. When particles from incubations were exposed to an anti-apo-B column, radiolabeled surface and core molecules originating from the CEME particles bound to the column. Particles eluted at low pH from the anti-apo-B column were irregularly shaped and had excess surface material as judged by electron microscopy. Incubation of CEME with LDL in the presence of 3 M KBr or 4% bovine serum albumin did not alter the interaction of the particles. However, incubation of CEME with LDL in the presence of apo-A-I (2:1 CEME cholesterol-to-apo-A-I mass ratio) greatly reduced the interaction of the LDL and CEME particles. We conclude that the incubation of CEME with isolated LDL resulted in particle fusion that was prevented by apo-A-I.

Apolipoprotein A-I↗
PubMed1985

Bone marrow transplantation in the treatment of sickle cell anemia.

The possibility of using bone marrow transplantation to treat selected patients with sickle cell anemia has recently been raised by the effectiveness of this approach in an 8-year-old girl suffering from both acute myeloblastic leukemia and sickle cell anemia. The child's sickle cell anemia was converted to the donor's sickle cell trait and she remains in complete remission from her leukemia 22 months following transplantation. This paper considers the therapeutic implications of this child's progress and discusses the major immunological complications, particularly graft-vs.-host disease, which currently limit the more widespread use of marrow transplantation in the therapy of sickle cell anemia.

Anemia, Sickle Cell↗
PubMed1985

Effects of the degree of saturation of dietary fat on the hepatic production of lipoproteins in the African green monkey.

The cholesteryl ester content of plasma low density lipoproteins (LDL) in monkeys has previously been shown to be related to the rate of hepatic cholesterol secretion and cholesteryl ester content of newly secreted lipoproteins in the isolated perfused liver. In the present studies, African green monkeys were fed diets containing cholesterol and 40% of calories as either butter or safflower oil in order to determine the effects of saturated versus polyunsaturated dietary fat on hepatic lipoprotein secretion. The rate of cholesterol accumulation in liver perfusates was correlated with the size of the donor's plasma LDL, but for any rate, a smaller plasma LDL was found in donor animals of the safflower oil group than in those of the butter group. Hepatic very low density lipoproteins (VLDL) were smaller in the safflower oil group but contained more cholesteryl ester and fewer triglyceride molecules per particle than those from the butter group. Livers from the safflower oil group contained more cholesteryl ester and less triglyceride than those from the butter group. The cholesteryl ester percentage composition of hepatic VLDL resembled that of the liver in each group. The data show that dietary polyunsaturated fat decreased plasma LDL size even though it increased the cholesteryl ester content of lipoproteins secreted by the liver. Therefore, intravascular formation of plasma LDL from hepatic precursor lipoproteins appears to include the removal of relatively greater amounts of cholesteryl esters from the precursor lipoproteins in polyunsaturated fat-fed animals.

Animals↗