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Biomedical subjects

R J Jones

Publications and source records attributed to R J Jones.

At least 145 records · Page 8Linked to original sources
PubMed1989

Association of hepatic veno-occlusive disease with interstitial pneumonitis in bone marrow transplant recipients.

Hepatic veno-occlusive disease (HVOD) and interstitial pneumonitis (IP) are both widely regarded as toxicities of intensive cytoreductive therapy, but their association has not been previously examined. Risk factors for IP were evaluated in 154 patients given intensive cytoreductive therapy followed by allogeneic bone marrow transplantation during a 2 1/2 year period. IP occurred in 68 patients; HVOD occurred in 39. The actuarial incidence of IP in patients with VOD was 71% and 45% in those without VOD (p = 0.0002). In multivariate analysis, the diagnosis of hematologic malignancy (p less than 0.001), the occurrence of HVOD (p less than 0.01), and pretransplant CMV seropositivity (p less than 0.02) were significantly associated with IP. The individual relative risks for IP of presence to absence of these factors was 4.5 for the diagnosis of hematologic malignancy, 2.1 for HVOD, and 1.9 for CMV seropositivity. Pulmonary veno-occlusive disease (PVOD), a previously rare observation, was noted at autopsy in 1/5 (20%) patients with HVOD alone, 6/20 (30%) patients with IP alone, and 10/14 (71%) of patients with both HVOD and IP. The association of HVOD and IP is supportive of the concept that toxic effects of cytotoxic therapy have a major role in pathogenesis of HVOD and IP.

Anemia, Aplastic↗
PubMed1988

Microtubule changes and cytotoxicity in leukemic cell lines treated with taxol.

Taxol, a diterpenoid plant product that enhances the polymerization of tubulin, is currently entering clinical trials in the treatment of human leukemia. In order to develop an in vitro assay to predict tumor sensitivity to taxol, human leukemic cell lines were exposed to clinically achievable concentrations of taxol for relevant exposure periods. Changes in microtubules visualized by indirect immunofluorescence were compared to drug sensitivity measured by a clonogenic assay. Taxol produced either multiple mitotic asters in G2/M or microtubule bundling throughout the cell cycle. In cells that were relatively resistant to taxol, microtubule bundling was reversible while microtubule bundling in relatively sensitive cells persisted in the presence or absence of taxol. In contrast, aster formation was unrelated to cytotoxicity in any cell line. In the future, these microtubule effects may be useful in predicting the chemotherapeutic efficacy of taxol.

Alkaloids↗
PubMed1988

Prediction of the ability to purge tumor from murine bone marrow using clonogenic assays.

The development of potential purging regimens for autologous bone marrow transplantation has been limited by the inability to predict the antitumor activity of these regimens at doses which will allow engraftment. We describe an in vitro model which estimates the in vivo efficacy of potential purging regimens in mice. The log kill of clonogenic L1210 cells after in vitro incubation with graded doses of 4-hydroperoxycyclophosphamide and vincristine (alone or in combination) was linearly related to the incubation dose of drugs. Clonogenic assays could only directly demonstrate about three logs of cell kill. However, the log linear dose-response allowed the extrapolation of cell kill for doses of drugs whose kill could not be determined directly. The extrapolated cell kill accurately predicted the in vitro activity of the drugs as established by determining the survival of B6D2F1 mice given injections of the drug-treated L1210 cells. Lethally irradiated B6D2F1 mice were given injections of mixtures of syngeneic bone marrow and L1210 cells purged with a combination of 4-hydroperoxycyclophosphamide and vincristine. Combining the results of in vitro granulocyte-macrophage colony-forming unit and clonogenic L1210 sensitivities to this drug combination predicted the survival of mice and, therefore, the effectiveness of the purging regimen.

Animals↗
PubMed1988

Long-term in vitro culture of wheat grains.

Wheat (Triticum aestivum, Triticum durum) grains were excised immediately following fertilization and cultured until maturity. A rachis fragment attached to the grain was required to ensure an increase in grain size for the first 10 days following fertilization. A (14)C-labeling study revealed that 8-day-old grains accumulated more dry matter into the ethanol-insoluble fraction when grown on agar rather than when immersed in liquid medium. Light enhanced the absorption of sucrose from the medium only in the latter case. In agar-based culture, when no contact was made between the grain surface and the medium, peeling off the outer pericarp layers increased sugar absorption, leading to a threefold increase in the amount of accumulated dry matter in the ethanol-insoluble fraction. Culturing of wheat grains with attached rachis fragment and peeled pericarp is recommended for maximum in vitro growth.

Journal Article↗
PubMed1987

Remission of rheumatoid arthritis with the successful treatment of acute myelogenous leukemia with cytosine arabinoside, daunorubicin, and m-AMSA.

We describe 2 patients in whom a sustained remission of longstanding rheumatoid arthritis occurred with treatment for acute myelogenous leukemia (cytosine arabinoside, daunorubicin, and m-AMSA), even though both illnesses had been refractory to therapy with standard disease-modifying agents. These 2 patients represent the first successful treatment of rheumatoid disease using such an approach.

Amsacrine↗
PubMed1987

Venoocclusive disease of the liver following bone marrow transplantation.

Review of 235 consecutive patients undergoing bone marrow transplantation was performed in order to define the clinical syndrome of venoocclusive disease of the liver (VOD) in these patients. Analysis of all patients with histologically proven VOD revealed a consistent clinical syndrome of liver dysfunction occurring within the first 3 weeks after marrow infusion. This was characterized by hyperbilirubinemia peaking at greater than or equal to 2 mg/dl with at least 2 of 3 other findings: hepatomegaly, ascites, and 5% or greater weight gain. VOD developed in 22% (52 of 235). A persistently elevated aspartate aminotransferase (SGOT) prior to transplant was associated with an increased risk of developing VOD by multivariate analysis (P = 0.0003), and acute leukemia in first remission was associated with a decreased risk (P = 0.02). Neither the preparative regimen (busulfan and cyclophosphamide versus cyclophosphamide and total body irradiation) nor the type of graft (allogeneic versus autologous) influenced the occurrence. Twenty-four of these 52 patients (47%) died with VOD (10% of the entire group). This makes VOD the third leading cause of death in our allogeneic graft recipients, and the second leading cause in our patients receiving autologous transplants. VOD is a common complication of bone marrow transplantation and has a specific clinical presentation, which usually allows diagnosis without the need of liver biopsy.

Bone Marrow Transplantation↗
PubMed1987

Distribution of Abscisic Acid in Maize Kernel during Grain Filling.

The distribution of abscisic acid (ABA) within maize (Zea mays L.) kernels was studied in kernels from nontreated plants, from plants in which assimilate supply had been altered by source/sink manipulations, and in kernels cultured in vitro on ABA-free media. Prior to growth of the embryo, both the pedicel/placento-chalazal complex and the endosperm contained high concentration of ABA; however, the quantity of ABA in these tissues declined as the concentration in the embryo increased during the early stages of embryo growth. Peaks in the levels of ABA appeared to occur prior to and not concurrent with physiological events during grain filling. During most of the grain filling period, ABA concentration in the embryo was higher than that found in other kernel components. Altering assimilate supply by partial defoliation at two stages of development resulted in variable and transient effects on the relative distribution and concentration of ABA in kernel components. The concentration and distribution of ABA among components of kernels grown in vitro was similar to that observed for field-grown kernels. On the basis of these findings, in situ synthesis of ABA by kernel components is implicated and the putative role of ABA in the regulation of kernel development is discussed.

Journal Article↗
PubMed1987

In Vitro Sugar Transport in Zea mays L. Kernels : I. Characteristics of Sugar Absorption and Metabolism by Developing Maize Endosperm.

Short-term transport studies were conducted using excised whole Zea mays kernels incubated in buffered solutions containing radiolabeled sugars. Following incubation, endosperms were removed and rates of net (14)C-sugar uptake were determined. Endogenous sugar gradients of the kernel were estimated by measuring sugar concentrations in cell sap collected from the pedicel and endosperm. A sugar concentration gradient from the pedicel to the endosperm was found. Uptake rates of (14)C-labeled glucose, fructose, and sucrose were linear over the concentration range of 2 to 200 millimolar. At sugar concentrations greater than 50 millimolar, hexose uptake exceeded sucrose uptake. Metabolic inhibitor studies using carbonylcyanide-m-chlorophenylhydrazone, sodium cyanide, and dinitrophenol and estimates of Q(10) suggest that the transport of sugars into the developing maize endosperm is a passive process. Sucrose was hydrolyzed to glucose and fructose during uptake and in the endosperm was either reconverted to sucrose or incorporated into insoluble matter. These data suggest that the conversion of sucrose to glucose and fructose may play a role in sugar absorption by endosperm. Our data do not indicate that sugars are absorbed actively. Sugar uptake by the endosperm may be regulated by the capacity for sugar utilization (i.e. starch synthesis).

Journal Article↗
PubMed1987

In Vitro Sugar Transport in Zea mays L. Kernels : II. Characteristics of Sugar Absorption and Metabolism by Isolated Developing Embryos.

In vitro sugar transport into developing isolated maize embryos was studied. Embryo fresh and dry weight increased concomitantly with endogenous sucrose concentration and glucose uptake throughout development. However, endogenous glucose and fructose concentration and sucrose uptake remained constant. The uptake kinetics of radiolabeled sucrose, glucose, and fructose showed a biphasic dependence on exogenous substrate concentration. Hexose uptake was four to six times greater than sucrose uptake throughout development. Carbonylcyanide-m-chlorophenylhydrazone and dinitrophenol inhibited sucrose and glucose uptake significantly, but 3-O-methyl glucose uptake was less affected. The uptake of 1 millimolar sucrose was strongly pH dependent while glucose was not. Glucose and fructose were readily converted to sucrose and insoluble products soon after absorption into the embryo. Thus, sucrose accumulated, while glucose pools remained low. Based on the findings of this and other studies a model for sugar transport in the developing maize kernel is presented.

Journal Article↗
PubMed1987

Beneficial effect of a pharmacist refill evaluation clinic.

A study of 32 patients attending a pharmacist-run clinic was performed. This pharmacist refill evaluation clinic (PREC) assesses the continuation of maintenance drug therapy and is an alternative to the physician's clinic. This study evaluated total time spent at the clinic, reasons for refill requests, number of refills requested, number of requested refills approved, and number of physician consults and referrals required. The total clinic visit time at the PREC was 60 +/- 35.9 minutes versus a total time required at physicians clinic of 129 +/- 115.2 minutes. Of the patients treated at the PREC, 90.6% required no physician consult or referral. An estimated $135 savings in drug cost was approximated by the clinic during this small sample (a 30-day study), plus a difference in clinic fee that would amount to $1120 not including the difference in the pharmacist and physician's salaries. Other contributions attributed to this clinic were better patient compliance, accurate documentation of medication records, drug abuse surveillance, and drug therapy efficacy.

Ambulatory Care↗
PubMed1987

CFU-GM content of bone marrow graft correlates with time to hematologic reconstitution following autologous bone marrow transplantation with 4-hydroperoxycyclophosphamide-purged bone marrow.

Autologous bone marrow transplants (BMTs) can repopulate the hematologic system of patients treated with marrow-ablative chemotherapy and/or radiotherapy. However, treatment of the bone marrow graft to eliminate residual tumor cells prior to reinfusion can delay the return of peripheral blood elements, presumably from damage to or loss of hematopoietic stem cells responsible for hematologic recovery. To develop a model predictive of hematologic recovery, we studied the progenitor cell contents of 4-hydroperoxycyclophosphamide (100 micrograms/mL)-purged bone marrow grafts of 40 consecutive patients undergoing autologous BMT at this center. Granulocyte-macrophage colonies (CFU-GM) were grown from all grafts after treatment with this chemotherapeutic agent, but erythroid (BFU-E) and mixed (CFU-GEMM) colonies were grown from only 44% and 33% of the grafts respectively. The recovery of CFU-GM after purging ranged from 0.07% to 23%. The logarithm of CFU-GM content of the treated grafts was linearly correlated with the time to recovery of peripheral blood leukocytes (r = -0.80), neutrophils (r = -0.79), reticulocytes (r = -0.60), and platelets (r = -0.66). The CFU-GM content of purged autologous bone marrow grafts may reflect the hematopoietic stem cell content of the grafts and thus predict the rate of hematologic recovery in patients undergoing autologous BMT.

Adolescent↗
PubMed1987

Progenitor cell assays predict hematopoietic reconstitution after syngeneic transplantation in mice.

Hematopoietic reconstitution following syngeneic bone marrow transplantation with graded doses of untreated and drug-treated bone marrow was studied in B6D2F1 mice. Granulocyte-macrophage colony-forming units (CFU-GM) and spleen colony-forming units (CFU-S) showed similar in vitro drug sensitivities. Both the speed of hematologic recovery and survival of mice transplanted with untreated or drug-treated bone marrow were directly related to the number of CFU-GM or CFU-S transplanted. Similar hematologic recovery was seen for untreated marrow transplants and treated transplants that had similar CFU-GM or CFU-S content. There is a minimum number of transplanted CFU-GM or CFU-S that allows survival of lethally irradiated mice. This number is present in a marrow transplant containing the equivalent of 5 X 10(3) untreated cells or producing one to two spleen colonies. There also exists a maximum value for the number of hematopoietic progenitors in a marrow graft, above which the rate of hematologic recovery following transplantation is rapid and no detectable increase in the rate is seen with increasing CFU-GM or CFU-S content. The presence of this maximum value for transplanted progenitors and variations in culture techniques are probably the reasons previous studies have not always shown a correlation between CFU-GM content and hematologic recovery after bone marrow transplantation.

Animals↗
PubMed1987

Variability in 4-hydroperoxycyclophosphamide activity during clinical purging for autologous bone marrow transplantation.

We examined the effects of varying incubation conditions on the in vitro activity of 4-hydroperoxycyclophosphamide (4HC). 4HC activity against CFU-GM and against the K562 tumor cell line decreased with increasing the RBC concentration of the incubation mixture. Increasing the concentration of nucleated bone marrow cells in the incubation mixture also decreased the 4HC activity. Evaluation of 53 consecutive patients undergoing autologous bone marrow transplantation (BMT) revealed that the incubation RBC concentration during clinical purging showed a similar effect on CFU-GM recovery. Aldehyde dehydrogenase content of RBCs and nucleated marrow cells appears to be the cause of the inhibition of 4HC activity. Although there was no difference in individual CFU-GM sensitivity to 4HC among normals, previously treated patients undergoing autologous BMT showed significant variability in CFU-GM sensitivity to 4HC. The combined effects of incubation RBC concentration and individual patient 4HC sensitivity appear to account for most of the variability in CFU-GM recovery and speed of hematologic recovery after clinical purging with 4HC.

Bone Marrow↗
PubMed1987

Cardiovascular and risk factor evaluation of healthy American adults. A statement for physicians by an Ad Hoc Committee appointed by the Steering Committee, American Heart Association.

Cardiovascular disease is the major cause of death in American adults. The chief form of cardiovascular disease is coronary heart disease (CHD). Prevention of CHD depends on the identification of risk factors in asymptomatic individuals. The American Heart Association recommends that all adults be examined periodically for the presence of silent cardiovascular disease and coronary risk factors. The major risk factors for CHD are smoking, high blood pressure, and high blood cholesterol. Additional factors associated with CHD are high blood triglycerides, reduced levels of high-density lipoproteins, diabetes mellitus, obesity, sedentary lifestyle, and certain behavioral characteristics. Available data suggest that the predominance of CHD among Americans can be attributed to these risk factors, and increasing evidence indicates that appropriate modification of these factors will markedly reduce coronary risk. The purpose of this report is to identify the risk factors, indicate their relation to coronary disease, and recommend an approach to their detection in adults during periodic health examinations.

Adult↗
PubMed1986

Massive adrenal hemorrhage secondary to metastatic lung carcinoma.

The adrenal glands are frequently metastatic sites of lung and other primary neoplasms. These metastases are usually clinically occult and secondary adrenal hemorrhage is extremely rare. Two patients who developed massive adrenal hemorrhage secondary to metastatic lung carcinoma to the adrenal glands are presented.

Adenocarcinoma↗