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Biomedical subjects

R D Lackman

Publications and source records attributed to R D Lackman.

32 records · Page 2Linked to original sources
PubMed1990

Extremity osteosarcomas: intraarterial chemotherapy and limb-sparing resection with 2-year follow-up.

Twenty-eight consecutive patients with extremity osteosarcoma (24 stage II, four stage III) received their entire preoperative course of chemotherapy intraarterially in order to maximize local drug concentration and tumor shrinkage to facilitate limb-sparing resection. Eighteen tumors were located in the femur, seven in the tibia, two in the humerus, and one in the fibula. Most patients underwent two catheterizations; thus there was a total of 51 procedures. The average duration of each infusion was 10.4 days. There were eight procedure-related complications, but none precluded completion of intraarterial chemotherapy. Limb-sparing surgery was performed on 25 patients. At a mean follow-up of over 2 years, there was one local recurrence. Among limb-salvage patients with stage II disease, 90% (18 of 20) survived and 75% (15 of 20) are disease-free. Compared with patients from previous studies, this technique permits a high percentage of patients with osteosarcoma to undergo limb-sparing resection without compromise of local disease control or survival.

Adolescent↗
PubMed1989

Low-dose chemotherapy of desmoid tumors.

Eight patients with desmoid tumors, symptomatic, and none a candidate for conservative surgery, were treated with weekly vinblastine, maximum dose 10 mg/week, and methotrexate, maximum dose 50 mg/week. Symptomatic relief was obtained in all patients. Using Eastern Cooperative Oncology Group (ECOG) criteria, two patients had a complete remission, one of which has lasted for 30 months, four patients have had partial remissions, one patient has had a mixed response, and one patient who has been treated for only 4 weeks, a minimal response. Toxicity has been minor and transient. Chemotherapy appears to be an acceptable alternative to radical surgery in selected patients with desmoid tumors.

Adult↗
PubMed1987

Fibular reconstruction for giant cell tumor of the distal radius.

The management of giant cell tumors involving the distal radius has always been a difficult problem. After resection to eradicate a primary or recurrent lesion, transplantation of a nonvascularized fibular autograft was used in 12 patients. Of these patients, ten had good to excellent functional results. The procedure can restore a functionally useful wrist.

Adult↗
PubMed1986

Cellular immune response to human sarcomas: cytotoxic T cell clones reactive with autologous sarcomas. I. Development, phenotype, and specificity.

Human T cell clones cytotoxic for autologous sarcoma cell lines have been developed from patient JM with an osteogenic sarcoma, and from patients EG and RM with malignant fibrohistiocytoma. These clones were derived from the cocultivation of peripheral blood lymphocytes (PBL) with the respective patient's autologous irradiated established tumor cell lines (AIT). After two cycles of stimulation for 5 days in bulk culture, these "educated" lymphocytes were seeded at a density of 1 X 10(6) cells/well in 24-well plates and were cultured in the presence of highly purified natural IL 2 and AIT, the latter serving as a feeder layer. Cell numbers were reduced from the initial seeding density by one log each week until reaching a density of 10(2) cells. These cells were found to be stable in viability and cytotoxic activity, after which limiting dilution was then performed. Within 4 to 6 wk, clones were isolated with unique specificities. These clones were capable of proliferating to a total density of 10(9) cells/ml and maintained their specific cytotoxicity for more than 6 mo. Testing with a panel of target cells of various histotypes, cold-target inhibition assays, and blocking of cytotoxicity with anti-HLA monoclonal antibodies showed that the T cell clones recognize a common sarcoma-associated antigen and that the lysis is HLA restricted. Phenotypically, cytotoxic clones derived from JM were Leu-1+, Leu-2+, and Leu-3-, whereas those derived from EG exhibited either Leu-24 or Leu-3+ markers, the latter phenotype lacking cytotoxicity. RM exhibited mainly Leu-3+ clones with strong cytotoxicity. All were HNK-1- and HLA class II+, with less than 1% of cells of each clone stained by anti-TAC monoclonal antibody. The clones from each patient did not lyse autologous or allogeneic PBL, mitogen-induced T lymphoblasts, normal fibroblasts, cells isolated from benign neoplasms, carcinoma cells, Daudi B lymphoid cells, or K562 cells. With the exception of EG, all clones produced immune interferon in a range from 12 to 50 U/ml. The generation of long-term specific T cell clones can be used to further dissect the cellular immune response to sarcomas. Cytotoxic T cell clones have potential application for tumor immunotherapy.

Antigens, Neoplasm↗
PubMed1983

Stimulation of fatty acid utilization by sodium clofibrate in rat and monkey hepatocytes.

The acute effects of sodium clofibrate (NaCPIB) on the metabolism of [1-14C]palmitate, [1-14C]octanoate, [1-14C]butyrate, and [2-3H]glycerol by freshly isolated hepatocytes were tested to explore its mechanism of action. Labeled long-, medium-, and short-chain fatty acids were incorporated into all the major lipid classes and were oxidized to 14CO2 by the liver cells. The partitioning of labeled fatty acids from lipogenic towards oxidative pathways was inversely related to fatty acid chain length. [1-14C]Palmitate was incorporated mainly into cellular triglycerides and phospholipids; [1-14C]octanoate, mainly into triglycerides and free cholesterol; and [1-14C]butyrate, mainly into free cholesterol and phospholipids of the cells. NaCPIB (1-3 mM) rapidly stimulated the esterification of labeled palmitate or glycerol to triglycerides, but drug levels greater than 5 mM were inhibitory to esterification. NaCPIB (1 mM) increased the oxidation of [1-14C]palmitate to 14CO2 by either rat or monkey hepatocytes and enhanced the release of labeled lipids from [2-3H]glycerol-prelabeled cells into the extracellular medium. Accelerated [1-14C]octanoate incorporation into glycerolipids and sterols and increased [1-14C]octanoate conversion to 14CO2 were observed in rat liver cells incubated with 1 mM NaCPIB. In contrast, the same drug level stimulated the oxidation of [1-14C]butyrate to 14CO2 but greatly diminished its incorporation into hepatocellular sterols or glycerolipids. These results indicate that (a) NaCPIB acutely alters hepatic ultilization of fatty acids by actions at diverse loci; (b) these metabolic alterations vary with fatty acid chain length; and (c) these effects are probably due to rapid changes in biochemical regulatory mechanism and/or in substrate channelling within the cells. These data further suggest that the early hypolipidemic effect of the drug in rats and primates may be related to an enhanced hepatic oxidation of long-chain fatty acids, but cannot be attributed simply to a reduction in their esterification to complex lipids.

Animals↗
PubMed1983

Absence of the glycerol phosphate shuttle in the various zones of the growth plate.

UNLABELLED: The various zones of the growth plate of the rib of six-week-old male New Zealand White rabbits were obtained by means of a specially devised guillotine slicing apparatus. Cartilage slices from each zone were assayed enzymatically for activity of glycerol phosphate dehydrogenase by an adaptation of a fluorimetric technique based on the conversion of non-fluorescent resazurin to the highly fluorescent resorufin in the presence of nicotinamide adenine dinucleotide and the enzyme. No glycerol phosphate dehydrogenase activity was detectable in any zone of the growth plate, whereas control liver slices exhibited abundant enzyme activity. Thus the glycerol phosphate shuttle, one pathway whereby reducing equivalents are carried or shuttled from cytoplasmic nicotinamide adenine dinucleotide to the intramitochondrial respiratory chain, is entirely lacking in growth-plate chondrocytes. The lack of this enzyme, and the absence of the glycerol phosphate shuttle, may explain the high rate of lactate accumulation in the presence of ample oxygen concentration (aerobic accumulation) even though the Krebs cycle (tricarboxylic acid cycle) and electron transport are proceeding at normal rates. CLINICAL RELEVANCE: The growth plate is a complex structure whose metabolism is still not well understood. This study demonstrates that, in at least one metabolic pathway, the growth-plate chondrocyte does not resemble other normal cells. Only as we are able to formulate a more complete picture of the metabolism of the normal growth plate will be able to understand, and perhaps correct or prevent, those disease states in which growth-plate metabolism has bone away.

Animals↗
PubMed1981

Stimulated secretion of esterified lipids and VLDL by perifused hepatocytes.

This report describes a new method for investigation of hepatic metabolism by perifusion of medium through a batch of hepatocytes isolated from fed rats. Oxygenated medium flows by gravity through a hepatocyte-containing glass column that is immersed in 37 degrees C water bath. The effluent medium is then collected in consecutive aliquots in test tubes on ice. The pattern of export of esterified lipids, glucose, and VLDL by isolated liver cells into the perifusate was examined under both basal conditions and response to the infusion of certain metabolic stimulants. Perifusion of medium containing sodium clofibrate (1 mM and 10 mM levels) through lipid-prelabeled cells augmented the secretion of radioactive triacylglycerols that reached a maximal rate by about 30 min after exposure to this agent. Measurement of effluent glucose levels after perifusion of hepatocytes with media lacking glucose but containing a gluconeogenic precursor revealed steadily declining concentrations despite the addition of glucagon or epinephrine. Concomitantly, glycogen granules disappeared from the cytoplasm, but the cells retained intact ultrastructure after the course of perifusion. Protein-prelabeled hepatocytes released labeled VLDL into the perifusate, and this release was enhanced by prolonged exposure of the cells to medium containing palmitate (0.80 mM). The hepatocyte perifusion system thus offers a simple, reproducible method whereby hepatocellular secretory processes can be sequentially examined under carefully controlled basal and stimulated conditions.

Animals↗
PubMed1975

Rapid modulation of lipogenesis by clofibrate in rat and monkey hepatocytes.

Previous studies have proposed various possible mechanisms for the hypolipidemic actions of clofibrate. In the present study, isolated liver cells freshly prepared from rats and squirrel monkeys were used to investigate the acute effects of sodium clofibrate (sodium chlorophenoxyisobutyrate) on hepatic lipogenesis. Incubation of liver cells with levels of the drug (1 mM) known to lower plasma lipid level in vivo produced a rapid inhibition of [14C]acetate incorporation into cellular lipids. The degree of inhibition caused by the drug was not diminished by preincubation with an excess of unlabeled acetate. Conversion of [14C]acetate to 14CO2 was not significantly altered by sodium clofibrate at 1--3 mM levels, but was decreased at 5--10 mM levels. Incorporation of [14C]acetate into all lipid classes was suppressed by this agent, but inhibition of sterol synthesis was more pronounced than that of fatty acids. Sodium clofibrate (1 mM) reduced the synthesis of sterols from either labeled acetate or labeled mevalonate to a similar degree, but the decline was augmented in each case by a 30-min preincubation of the cells with sodium clofibrate. Addition of fatty acids to cell incubations stimulated sterol generation from [14C] acetate or from [3H] mevalonate, but did not reverse the inhibitory effects of the drug. These results suggest (a) the sodium clofibrate rapidly interferes with hepatic fatty acid and sterol synthesis by direct or indirect actions at diverse loci; (b) that these effects probably occur after acetyl-CoA formation and do not stem from precursor pool dilution; (c) that sodium clofibrate diminishes sterol production at post-mevalonic and perhaps also at pre-mevalonic sites; (d) that a similar pattern of inhibition occurs with sodium clofibrate in the presence of added fatty acids; and (e) that rat and primate livers demonstrate similar metabolic responses to the drug.

Acetates↗
PubMedDate not supplied

Isolated ophthalmic migraine in the differential diagnosis of cerebro-ocular ischemia.

Thirty-three of 129 patients who incurred isolated ophthalmic migraine had monocular attacks of scotomatous visual field loss. Fifteen of 33 patients with monocular attacks had immediate or remote evidence of vascular disease. Four patients had carotid bruits on the same side as the monocular attacks and low ophthalmodynamometer readings. One patient had ischemic optic neuropathy and two had atheromatous disease (advanced stage in one patient). Forty-five percent of the patients with monocular attacks and only 13% of the remaining patients with homonymous attacks had vascular complications. This represents an important finding even in such a small group of patients. It is felt that, whether the vascular problems are trigger mechanisms or coexistence pathology to the migraine-type attack, one should strongly suspect such an association when a patient describes a monocular attack and one should look for a possible vascular explanation other than migraine.

Age Factors↗