Search PubMed⌕ Search

Biomedical subjects

F L Johnson

Publications and source records attributed to F L Johnson.

At least 37 records · Page 2Linked to original sources
PubMed1993

Effects of chemotherapy and irradiation on the gonads.

As the survival of children with cancer improves, attention must now be focused on understanding and preventing long-term toxicities of treatment and improving the quality of survival. Gonadal toxicity is relatively common, particularly with radiation therapy and alkylating agents. Continued research into the pathogenesis and prevention of gonadal toxicities needs to be included in future treatment strategies for childhood cancer. This will require a multidisciplinary approach with input from pediatric hematologist/oncologists, radiation oncologists, and pediatric endocrinologists.

Adolescent↗
PubMed1993

Role of autotransplantation in neuroblastoma.

Neuroblastoma is the most enigmatic disease treated by pediatric oncologists. The same pattern of apparent metastatic spread is associated with a high rate of spontaneous regression in children under 1 year of age (stage IVS) but an invariably fatal course in older children. For these children with truly advanced neuroblastoma, recent studies have demonstrated that the possibility of complete remission and disease-free survival is increased with more intensive conventional combination chemotherapy. Supportive care with autologous marrow has enabled further significant dose escalation of cytotoxic therapy active against neuroblastoma, resulting in disease-free survival in between 25% and 50% of patients at 2 years, an improvement over historical experience with conventional chemotherapy. The development of more effective cytotoxic combinations active against neuroblastoma, improvements in ex vivo techniques to purge marrow of neuroblastoma cells, and the application of cytokines to hasten marrow recovery should further enhance the effectiveness of autotransplantation in the treatment of advanced neuroblastoma and further improve the chances for complete remission and longer remission duration. Whether this improved remission induction and duration will translate into an increased cure rate remains to be determined. Parallel advances in therapies not involving autologous marrow support will undoubtedly modify the role of autotransplantation in neuroblastoma. Currently, however, autotransplantation offers one potential solution to a major challenge in the treatment of advanced neuroblastoma--obtaining and maintaining complete remissions--and a promising basis for future therapeutic studies.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Hyperdiploidy arising from near-haploidy in childhood acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) of childhood is frequently characterized by a hyperdiploid karyotype. Typically, most of the affected chromosomes in the abnormal clone are present in three copies. We have studied two patients with hyperdiploid ALL whose leukemic cells were atypical in that all or most of the chromosomes were present in either two or four copies, raising a suspicion that the observed karyotype arose through duplication of chromosomes in a precursor cell with a near-haploid chromosome number. Analysis of restriction fragment length polymorphisms confirmed that both cases arose from a near-haploid cell; all informative disomic chromosomes tested had loss of heterozygosity. Furthermore, the hyperdiploid karyotypes did not arise via a perfect haploid cell with exactly 23 chromosomes, because tetrasomic chromosomes remained heterozygous. These two patients probably are classified best as near-haploid cases, which often are observed to have a co-existing hyperdiploid clone with a duplicated chromosome set. The distinction between typical hyperdiploidy and hyperdiploidy arising via a near-haploid cell may be clinically important, because the prognosis for patients with a hyperdiploid karyotype is favorable in comparison to that of patients with a near-haploid karyotype.

Adolescent↗
PubMed1992

Allogeneic marrow transplantation in the treatment of infants with cancer.

Marrow transplantation in infants with cancer present special challenges particularly because of the need to use conditioning regimens containing cytotoxic agents during a period of rapid somatic growth. An up-date of the largest study in children under 2 years of age treated by marrow transplantation for acute myeloblastic leukaemia, and a review of late effects experienced by older children, demonstrate the necessity to develop conditioning regimens which avoid total body radiation. Efforts to achieve this aim in the treatment of leukaemia are summarised.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Bone marrow transplantation for sickle cell disease. A study of parents' decisions.

BACKGROUND: Bone marrow transplantation has been shown to cure sickle cell disease, but it carries a 15 percent mortality risk. To determine whether parents would accept this risk to cure their children of sickle cell disease, we interviewed parents of children with sickle cell disease who were being followed in a university hospital clinic. METHODS: We assessed parents' attitudes by using questions based on the standard reference-gamble paradigm. After we gave them descriptions of bone marrow transplantation and graft-versus-host disease (GVHD), the parents were presented with a series of hypothetical situations. In the first situation, bone marrow transplantation was described as offering certain (100 percent) survival with cure of sickle cell disease. In subsequent descriptions, the mortality rate associated with bone marrow transplantation was increased by 5 percent increments. The parents indicated the highest mortality risk at which they would consent to the procedure in order to cure their children. RESULTS: In order to obtain a cure for their children, 36 of 67 parents (54 percent) were willing to accept some risk of short-term mortality, 25 of 67 (37 percent) were willing to accept at least the 15 percent short-term mortality risk we estimate to be the current figure for bone marrow transplantation, and 8 of 67 (12 percent) were willing to accept a short-term mortality risk of 50 percent or more. Nine parents (13 percent) said they would accept both a mortality risk of 15 percent or more and an additional 15 percent risk of GVHD. The parents' decisions were not related to the clinical severity of their children's illness. CONCLUSIONS: At current rates of mortality and morbidity with bone marrow transplantation, a substantial minority of the parents of children with sickle cell disease may consent to bone marrow transplantation for their children. Parental attitudes should be factored into decisions about whether to offer bone marrow transplantation to children with sickle cell disease.

Adolescent↗
PubMed1991

Immunoglobulin gene rearrangements in acute lymphoblastic leukemia with the 9;11 translocation.

The recurring chromosomal 9;11 translocation [t(9;11) (p22;q23)] typically is associated with acute monoblastic leukemia, but a number of patients with acute lymphoblastic leukemia also have been reported to have the t(9;11). To investigate the cell lineage in the latter cases, we analyzed DNA from the leukemic cells of an 8-year-old girl with acute lymphoblastic leukemia and a t(9;11) for rearrangements of the immunoglobulin and T-cell receptor genes. Rearrangements of both immunoglobulin heavy-chain loci and of one lambda light-chain gene were detected, as well as deletions affecting both alleles of the kappa light-chain genes; T-cell receptor genes were in germline configuration. These results provide further evidence that the 9;11 translocation is not limited to myeloid lineage leukemia and may be observed in acute lymphoblastic leukemia.

Child↗
PubMed1991

Dietary fish oil effects on biliary lipid secretion and cholesterol gallstone formation in the African green monkey.

We studied two groups of adult male African green monkeys to assess the effects of dietary fish oil on biliary lipid secretion and cholesterol gallstone formation. One group was fed 0.8 mg cholesterol/kcal and 42% of calories as fat with half of the fat calories derived from lard; the other group was fed a similar diet except for the isocaloric substitution of menhaden oil for lard. After 2 1/2 to 3 yr, necropsies were performed and the presence of gallstones was determined. Gallbladder bile specimens were analyzed for cholesterol saturation index, as well as for bile acid species and biliary phospholipid fatty acid composition. Our results showed that 67% of animals fed the lard diet had cholesterol gallstones compared with only 22% of animals in the group fed the fish oil diet (p = 0.08). The cholesterol saturation index of gallbladder bile also tended to be higher in the lard-fed group (1.15 +/- 0.11) compared with the fish oil-fed group (0.86 +/- 0.09, p = 0.06). No differences between the two dietary groups were noted in the percentages of the various types of bile acids. However, a greater percentage of omega-3 fatty acids and a lesser percentage of 18:1, 18:2 and 20:4 fatty acids were found in the biliary phospholipids from the fish oil-fed group compared with the lard-fed group. Biliary lipid secretion rates were then measured during isolated recirculating liver perfusion performed with a constant sodium taurocholate infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Plasma HDL cholesterol concentrations are correlated to bile cholesterol saturation index in the African green monkey.

In an attempt to determine if plasma lipoprotein concentrations correlate with the bile cholesterol saturation index in the African green monkey, we have studied a group of adult male animals available from a long-term study investigating the effects of dietary fat and cholesterol on cholesterol metabolism and atherosclerosis. The animals were fed diets containing 0.8 mg cholesterol/kcal or 0.03 mg cholesterol/kcal for five years. Within each dietary cholesterol group, animals received 42% of dietary calories as fat, enriched with either saturated or polyunsaturated fat. Using stepwise multiple linear regression, high density lipoprotein (HDL) cholesterol concentration was found to be the best plasma lipid predictor of the bile cholesterol saturation index. When the cholesterol saturation index of a fasting gallbladder bile specimen was compared to the plasma HDL cholesterol level for individual animals, a significant positive correlation was noted for animals fed polyunsaturated fat, (r = 0.68) and for animals fed saturated fat (r = 0.72). For any value of HDL cholesterol, however, the cholesterol saturation index was higher in animals fed polyunsaturated fat compared to saturated fat. Since plasma HDL cholesterol levels were positively correlated with the bile cholesterol saturation index in adult male African green monkeys, we conclude that a metabolic link exists between plasma HDL cholesterol concentrations and bile cholesterol saturation, perhaps due to enhanced delivery of cholesterol to the liver by HDL.

Animals↗
PubMed1991

Granulocytic sarcoma of the ileum treated by bone marrow transplantation.

An 8-year-old boy with a granulocytic sarcoma of the proximal ileum metastatic to mesenteric lymph nodes was placed into complete remission with surgical excision of the primary tumor and conventional induction chemotherapy with daunorubicin and cytosine arabinoside. He was then treated with high dose cytosine arabinoside, fractionated total body irradiation, and allogeneic marrow transplantation from his 22-month-old brother who was completely matched at the major histocompatibility complex. Methotrexate was given following the transplant to prevent graft-versus-host disease (GVHD). His post-transplantation course was complicated by a transient autoimmune hemolytic anemia related to an ABO blood group incompatibility and hepatic fungal microabscesses which responded to Amphotericin therapy. Four years following the transplant the patient remains in complete remission. The prognosis for patients with granulocytic sarcoma has been poor although, perhaps, improved over the past decade. This is the first published case report of successful treatment of a granulocytic sarcoma of the ileum by allogeneic marrow transplantation.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Allogeneic bone marrow transplantation in a program of intensive sequential chemotherapy for children and young adults with acute nonlymphocytic leukemia in first remission.

Eighty-seven consecutive children and young adults with acute nonlymphocytic leukemia (ANLL) were treated uniformly with induction chemotherapy based on daunorubicin and cytarabine (ara-C), with the addition of etoposide (VP-16) and azacytidine (5-Az) for refractory patients. Of the 65 patients who entered complete remission, 42 were eligible for assessment of response to intensive chemotherapy consisting of four pairs of drugs administered in sequential fashion. Nineteen others with available histocompatibility locus antigen (HLA)-compatible donors were assigned to receive allogeneic bone marrow transplants within 16 weeks from their dates of complete remission. Durations of continuous complete remission (CCR) in the two groups were not significantly different at a median follow-up time of 6 years (P = .30 by log-rank analysis). Kaplan-Meier estimates of CCR probabilities (+/- SE) at 6 years were 43% +/- 13% (transplantation) and 31% +/- 7% (sequential chemotherapy). Postremission failures in the sequential chemotherapy group resulted from bone marrow relapse in 23 of 29 patients (79%), whereas in the transplantation group, failures were equally divided between marrow relapse and transplantation-related complications of graft-versus-host disease (GVHD) or infection due to the immunosuppressive effects of ablative chemotherapy. Comparison of hematologic remission curves indicated a significant advantage for marrow transplantation in terms of systemic leukemia control (P = .06). Thus, in programs of intensive chemotherapy of the type described here, allogeneic marrow transplantation should be seriously considered as alternative therapy for patients in first remission who have an HLA-matched sibling donor, provided that effective methods for control of transplant-related complications are available.

Adolescent↗
PubMed1990

Role of bone marrow transplantation in childhood lymphoblastic leukemia.

Allogeneic bone marrow transplantation is the only therapy introduced in the past 2 decades that has offered a better prognosis for children with ALL who have suffered a marrow relapse within 18 months of starting therapy. Currently, 40 to 50% of such patients are obtaining long remissions and are potentially cured by marrow transplantation. This therapy's effectiveness, however, is diminished by the problems of acute and chronic graft-versus-host disease, infection, and relapse. Further impact of marrow transplantation in the treatment of ALL awaits (1) more effective antileukemic preparative regimens or post-transplant antileukemic strategies, (2) less toxic preparative regimens to decrease the incidence of early and late effects, (3) more effective means of preventing and treating graft-versus-host disease, (4) the ability to safely perform mismatched marrow transplantation, and (5) more effective means of purging leukemic cells from remission bone marrow to expand the role of autologous marrow transplantation.

Bone Marrow Transplantation↗
PubMed1990

Effect of fish oil diet on hepatic lipid metabolism in nonhuman primates: lowering of secretion of hepatic triglyceride but not apoB.

African green monkeys were fed diets containing either 11% (by weight) fish oil or lard for 2.5 yr. To test the hypothesis that fish oil decreases hepatic secretion of triglyceride (TG) and apoB, livers from these animals were perfused with a fatty acid mixture [85% (w/w) oleate containing [14C]oleate and 15% n-3 containing [3H]eicosapentaenoic acid (EPA)] at a rate of 0.1 mumol fatty acid/min per g liver. Liver perfusate was sampled every 30 min during 4 h of recirculating perfusion. The concentration of triglyceride was similar for livers of animals of both groups and there was no difference between groups in the extent of incorporation of [3H]EPA or [14C]oleate into hepatic TG. While the secretion rate for the mass of TG was less in the fish oil-fed group (8.3 +/- 2.5 vs 18.3 +/- 4.4 mg/h per 100 g liver, P less than 0.05), the apoB secretion rate was similar (0.92 +/- 0.15 vs 1.01 +/- 0.13 mg/h per 100 g liver). Significantly less [3H]EPA was incorporated into secreted TG in the fish oil group (0.4 +/- 0.1 vs 1.0 +/- 0.1% infused dose/h; P less than 0.01). The rate of secretion of [14C]TG was similar for both groups (1.3 +/- 0.3 vs 1.4 +/- 0.1% infused dose/h for fish oil and lard groups, respectively). No significant diet-related differences in [3H]TG or [14C]TG fatty acid specific activity were observed for perfusate TG or hepatic TG. After perfusion, livers from fish oil-fed monkeys contained significantly more [3H]EPA in hepatic phospholipid than livers from lard-fed monkeys (19.5 +/- 1.8 vs 11.4 +/- 1.7% infused dose; P less than 0.01) although hepatic phospholipid mass concentrations were similar. The liver phospholipids of the fish oil group were enriched in n-3 fatty acid mass and were relatively depleted of oleate and linoleate. We conclude that although apoB secretion was unaffected, dietary fish oil significantly decreased hepatic TG secretion through relatively poor utilization of EPA for the synthesis of TG destined for secretion in VLDL; at the same time, increased incorporation of [3H]EPA into hepatic phospholipid accompanied the decreased incorporation into secreted TG and these events may be coupled.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Studies on the expression of genes encoding apolipoproteins B100 and B48 and the low density lipoprotein receptor in nonhuman primates. Comparison of dietary fat and cholesterol.

African green monkeys were fed diets containing low and moderate cholesterol concentrations with either polyunsaturated or unsaturated fat as 40% of calories. Plasma total cholesterol, low density lipoprotein (LDL) cholesterol, and apoB concentrations generally were higher in animals fed (a) the higher dietary cholesterol concentration and (b) saturated fat. At necropsy, liver and intestine were removed, and measurement of mRNAs for LDL receptors (liver) and for apolipoprotein B (liver and intestine) was done. Monkey small intestine mucosa made exclusively apoB48 while the liver made only apoB100, although apoB mRNA in both tissues was the same size (14 kilobases). No dietary cholesterol or fat effects were found for apoB mRNA abundance in the liver, while the animals fed the higher dietary cholesterol level had 50% lower levels of hepatic LDL receptor mRNA. In a separate group of animals, livers were perfused and the rate of apoB secretion was measured. No dietary fat effect on apoB secretion rate was found, and no relationship between plasma LDL cholesterol concentration and the rate of hepatic apoB production existed. These findings support the idea that the dietary factors that increase LDL concentrations act by reducing clearance of apoB-containing particles rather than by increasing production of these lipoproteins. Hepatic LDL receptor mRNA was similar in abundance in polyunsaturated fat and saturated fat-fed animals, suggesting that the difference in plasma cholesterol concentration between these groups is not mediated via effects on LDL receptor mRNA abundance. The level of intestinal apoB mRNA was about 30% higher in animals fed the moderate dietary cholesterol concentration. Earlier studies have shown that more cholesterol is transported in chylomicrons from the intestine when dietary cholesterol levels are higher, and the increased intestinal apoB mRNA abundance may reflect increased intestinal cholesterol transport and chylomicron apoB48 production.

Animals↗
PubMed1989

Delivery of high-density lipoprotein free and esterified cholesterol to bile by the perfused monkey liver.

The movement of cholesterol from high-density lipoproteins (HDL) into bile has been studied using perfused livers from cholesterol-fed African Green monkeys. Mass amounts of HDL were isolated from the plasma of African Green monkeys and were doubly labeled with either 125I-apolipoprotein and [3H]cholesteryl ester or with [3H]cholesteryl ester and [14C]cholesterol. For 3 h of perfusion HDL-free cholesterol was cleared from perfusate at a faster rate than HDL ester cholesterol which, in turn, was cleared at a faster rate than HDL protein. [14C]cholesterol from HDL appeared in biliary bile acids and cholesterol at a higher rate than [3H]esterified cholesterol from HDL. The specific activities of biliary [14C]cholesterol and HDL-free [14C]cholesterol had equilibrated by 60 min of perfusion, although the specific activity of whole liver free [14C]cholesterol was still only 46% of that in bile at 180 min of perfusion. In contrast, the specific activity of total liver free [3H]cholesterol was equal to that of biliary [3H]cholesterol by 180 min of perfusion. We conclude that, in this primate model, HDL-free cholesterol enters into a hepatic compartment that communicates with biliary cholesterol and bile acid precursor pools more efficiently than with other liver pools of cholesterol, whereas HDL-esterified cholesterol appears to mix with all liver pools with equal efficiency. Overall, these data support the concept of compartmentalization of cholesterol in the liver.

Animals↗
PubMed1989

Fish oil decreases hepatic cholesteryl ester secretion but not apoB secretion in African green monkeys.

Two groups of African green monkeys were fed diets containing 40% of calories as fat with half of the fat calories as either fish oil or lard. The fish oil-fed animals had lower cholesterol concentrations in blood plasma (33%) and low density lipoproteins (LDL) (34%) than did animals fed lard. Size and cholesteryl ester (CE) content of LDL, strong predictors of coronary artery atherosclerosis in monkeys, were significantly less for the fish oil-fed animals although the apoB and LDL particle concentrations in plasma were similar for both diet groups. We hypothesized that decreased hepatic CE secretion led to the smaller size and reduced CE content of LDL in the fish oil-fed animals. Hepatic CE secretion was studied using recirculating perfusion of monkey livers that were infused during perfusion with fatty acids (85% 18:1 and 15% n-3) at a rate of 0.1 mumol/min per g liver. The rate of cholesterol secretion was less (P = 0.055) for the livers of fish oil versus lard-fed animals (3.3 +/- 0.5 vs. 6.0 +/- 1.2 mg/h per 100 g, mean +/- SEM) but the rate of apoB secretion was similar for both groups (0.92 +/- 0.15 vs. 1.01 +/- 0.13 mg/h per 100 g, respectively). The hepatic triglyceride secretion rate was also less (P less than 0.05) for the fish oil-fed animals (8.3 +/- 2.5 vs. 18.3 +/- 4.4 mg/h per 100 g). Liver CE content was lower (P less than 0.006) in fish oil-fed animals (4.1 +/- 0.8 vs. 7.4 +/- 0.7 mg/g) and this was reflected in a lower (P less than 0.04) esterified to total cholesterol ratio of perfusate VLDL (0.21 +/- 0.045 vs. 0.41 +/- 0.06). The hepatic VLDL of animals fed fish oil had 40-50% lower ratios of triglyceride to protein and total cholesterol to protein. From these data we conclude that livers from monkeys fed fish oil secreted similar numbers of VLDL particles as those of lard-fed animals although the hepatic VLDL of fish oil-fed animals were smaller in size and relatively enriched in surface material and depleted of core constituents. Positive correlations between plasma LDL size and both hepatic CE content (r = 0.87) and hepatic VLDL cholesterol secretion rate (r = 0.84) were also found.(ABSTRACT TRUNCATED AT 400 WORDS)

Analysis of Variance↗
PubMed1989

A new filtration system for bone marrow transplantation. Clinical and laboratory studies.

A new method of filtering marrow obtained from marrow donors during marrow transplantation is described. The technique involves a small reusable filter unit and provides a simple, inexpensive, and fast means of filtering marrow in a predominantly closed system prior to infusion into the marrow recipient. In vitro studies of marrow from 10 donors showed no reduction in granulocytemacrophage or erythroid progenitors following filtration. Clinical studies of 75 patients receiving marrow filtered by this system showed no untoward effects or interference with engraftment. We conclude that this predominantly closed filtration system is efficient and should be further evaluated in marrow transplantation.

Adolescent↗