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Biomedical subjects

L M Glode

Publications and source records attributed to L M Glode.

At least 55 records · Page 3Linked to original sources
PubMed1984

Autologous marrow transplantation for patients with chronic myelogenous leukemia (CML) in blast crisis.

Even patients with chronic myelogenous leukemia (CML) in blast crisis were treated with chemotherapy, followed by infusion of autologous bone marrow that had been collected during the chronic phase of the disease and cryopreserved at -198 degrees C. The mean age of the nine females and two males in this study was 34 years with an average duration of the chronic phase of the disease of 5.5 years. Seven out of the 11 patients had a splenectomy prior to intensive chemotherapy. The median survival of the first four patients who received 6-thioguanine, cytosine arabinoside, daunorubicin (TAD) chemotherapy was 2.6 weeks and no patient reachieved the chronic phase of CML. The second group of seven patients received more intensive chemotherapy (MAdHAT), which included melphalan 30 mg/m2 days 1, 2, and 3; Adriamycin 50 mg/m2 intravenously (iv) day 1, hydroxyurea 1500 mg/m2 by mouth for 5-7 days, cytosine arabinoside 100 mg/m2 continuous infusion for 5-7 days, and VM-26 100 mg/m2 iv on day 3. Six out of these seven patients reachieved chronic phase CML after bone marrow reinfusion. The median survival was 29.9 weeks for all patients and 33 weeks for the six patients who reachieved chronic phase CML. All patients subsequently died of recurrent blast crisis. There was no correlation between the time of bone marrow storage and the duration of subsequent chronic phase CML. These studies have shown that autologous bone marrow transplantation after high-dose chemotherapy can result in bone marrow engraftment with reestablishment of chronic phase CML, and prolongation of survival.

Adult↗
PubMed1984

Tumor lysis syndrome following VP-16-213 in chronic myeloid leukemia in blast crisis.

Several recent reports have emphasized the potentially serious and often fatal acute metabolic complications following cytotoxic chemotherapy in both solid tumors and leukemias. We present here a case of chronic myeloid leukemia in blast crisis who developed an acute tumor lysis syndrome following a single dose of VP-16-213 (Etoposide).

Adult↗
PubMed1984

Long term effects of administration of a gonadotropin-releasing hormone superagonist analog in men with prostatic carcinoma.

Administration of the superagonist analog of GnRH, D-Leu6-GnRH proethylamide, profoundly reduced plasma LH, FSH, testosterone, and dihydrotestosterone levels when given for 6-11 weeks to adult men with prostatic carcinoma. Since patients with prostatic carcinoma can be expected to receive this analog for as long as 3-4 yr, we questioned whether the same degree of reduction could be maintained during chronic administration. In 22 men who had received D-Leu6-GnRH proethylamide for at least 1 yr, LH and testosterone remained at the initial low levels. Plasma dihydrotestosterone concentrations, on the other hand, gradually fell further with long term administration. FSH levels reached a nadir of 5.7 +/- 0.94 (+/- SEM) mIU/ml at 10-11 weeks. Unexpectedly, the plasma levels of this gonadotropin then gradually increased, and between 25 and 97 weeks were approximately 10-15 mIU/ml. This pattern occurred identically in patients receiving either 1 or 10 mg D-Leu6-GnRH proethylamide daily. These data indicate persistent suppression of LH and androgen levels during prolonged therapy and suggest that D-Leu6-GnRH-induced "medical castration" can be maintained with chronic administration.

Aged↗
PubMed1983

Detection of melanoma cells in bone marrow using monoclonal antibodies. A comparison of fluorescence activated cell sorting (FACS) and conventional immunofluorescence (IF).

Seven different human melanoma cell lines have been tested for the presence of melanoma associated antigen p97. The sensitivity of membrane immunofluorescence assays for the antigen was increased by using a mixture of antibodies to several epitopes of p97. Six of eight melanoma lines were strongly positive. Normal bone marrow was negative. When cultured p97-positive melanoma cells were added to normal marrow, the authors were able to detect 5% contamination, by fluorescence-activated cell sorting (FACS) and immunofluorescence (IF). No melanoma cells were found in one fresh and nine frozen bone marrow specimens of melanoma patients (including two with known positive marrow by routine histologic study) evaluated for autologous bone marrow transplantation after high-dose chemotherapy.

Antibodies, Monoclonal↗
PubMed1983

Cystathionase: a potential cytoplasmic marker of hematopoietic differentiation.

Cysteine auxotrophy and absence of cystathionase (CSE) has been associated with certain human and rodent leukemic cell lines. To determine whether this state was a marker of malignant transformation or of cellular differentiation, CSE content was measured in 16 well characterized human leukemia-lymphoma cell lines. Enzyme was easily detected in several lines but its level did not correlate with a proposed scheme of differentiation based on cell-surface markers. However, the apparent absence of enzyme in human bone marrow CFU-C determined by growth experiments suggests reduced levels of CSE may be a marker of cytoplasmic immaturity.

Bone Marrow Cells↗
PubMed1983

Familial leukemia and aplastic anemia associated with monosomy 7.

A kindred is described in which eight of 14 patients in one generation had acute nonlymphocytic leukemia or aplastic anemia either alone or terminating in acute nonlymphocytic leukemia. The proband and two siblings in one branch of this kindred presented with aplastic anemia, whereas acute nonlymphocytic leukemia was the presenting feature in the other two branches. Karyotypic evolution from a normal karyotype to monosomy 7 was demonstrated in the proband, and group C monosomy was seen in two other patients. The proband's serum sample inhibited in vitro growth of normal bone marrow colonies. The occurrence of hematologic disease in this kindred appears to be the result of a maternally transmitted trait, and persons younger than 30 years of age appear to have the highest risk of hematologic disease.

Adolescent↗
PubMed1983

A rat model for chemotherapy-induced male infertility.

The effects of chronic administration of cyclophosphamide and procarbazine on testicular function in the rat were examined. Cyclophosphamide produced disruption of the normal spermatogenic architecture that was dose and time dependent. Total ablation of the germinal epithelium was not achieved. Procarbazine produced more specific testicular damage. Multiple weekly injections of 100-200 mg/kg of procarbazine caused complete destruction of the spermatogenic cells, with no effect on Sertoli cells. Treated animals remained infertile for more than 4 months and showed no histologic evidence of recovery. This model may be useful for examining possible mechanisms to prevent spermatogenic damage associated with cancer chemotherapy in man.

Animals↗
PubMed1982

Use of monoclonal antibody to increase sensitivity and specificity in quantitative immunodiffusion assays.

A mouse monoclonal antibody has been produced which recognizes human liver gamma-cystathionase, Radioiodination of the monoclonal antibody facilitated its use in combination with non-specific precipitating rabbit antisera in classical immunodiffusion assays. The technique may have broad applicability in the detection and quantitation of rare antigens which are difficult to purify but easily recognizable in immunodiffusion assays. It may also be used for the initial detection of monoclonal antibodies to unique antigens of interest.

Animals↗
PubMed1982

Treatment of advanced malignant melanoma with high-dose chemotherapy and autologous bone marrow transplantation. Preliminary results--Phase I study.

Thirteen patients with advanced (Stage III) malignant melanoma have been treated with high-dose chemotherapy (nitrogen mustard or a combination of BCNU and melphalan) combined with autologous, nonfrozen, bone marrow transplantation. Three patients (24%) achieved a complete remission and are currently alive and free of disease without further therapy at 26, 60, and 73 weeks. Five patients (38%) achieved partial remissions and five patients (38%) had no response. There was no difference in the response rate to nitrogen mustard and the BCNU-melphalan combination. Severe side effects to nitrogen mustard, however, precluded its further use in this study. The major cause of death in patients was intracerebral metastases, raising the question of prophylactic brain irradiation in future studies. Studies of the recovery rate of peripheral blood neutrophil, platelet, and peripheral blood and bone marrow CFU-C suggest that autologous bone marrow infusion may be of benefit in shortening hematopoietic recovery following intensive chemotherapy.

Adolescent↗
PubMed1982

Autologous bone marrow transplantation in the therapy of small cell carcinoma of the lung.

Ten patients with small cell carcinoma of the lung were entered into a chemotherapeutic treatment program consisting of cyclophosphamide, vincristine, Adriamycin, and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea. Two courses of combination chemotherapy were administered to each patient followed by a third course with the same doses of drugs used on Course 2 but with autologous bone marrow transplantation given 24 to 48 hr after drug infusion. No differences could be detected between Courses 2 and 3 in terms of the magnitude, timing, or degree of myelosuppression. Serial bone marrow biopsies documented a progressive decline in granulocyte-macrophage colony-forming units in culture per mg bone marrow medullary core from 138 +/- 179 (S.D.) prior to chemotherapy to 7 +/- 11 after the marrow transplant recovery (p = 0.05). These data suggest that autologous bone marrow transplantation does not reduce the myelosuppression seen following the drugs used in this study at the dosages used. Autologous bone marrow transplantation may be useful only in the setting of marrow lethal therapy. Its usefulness in shortening recovery time from nonlethal therapy appears questionable.

Antineoplastic Agents↗
PubMed1981

Cysteine auxotrophy of human leukemic lymphoblasts is associated with decreased amounts of intracellular cystathionase protein.

A series of human lymphoblastoid cell lines derived from nonleukemic donors are known to be cysteine prototrophs (cys+), while several lymphoblastoid lines derived from leukemic donors are cysteine auxotrophs (cys-). We have tested representative cell lines of each type for their content of cystathionase enzyme activity by a specific catalytic assay and their total cystathionase protein content by immunoprecipitation of in vivo labeled protein. There was a close correlation between the cellular content of the enzyme as determined in the two assays. Specifically, those cys+ lines having readily measureable enzyme by catalytic assay were found to contain significantly higher levels of immunoprecipitable Mr 43 000 cystathionase subunit than those cys- lines tested which were depleted in active enzyme. Thus, the absolute cysteine requirement of the leukemic, cys- cell lines tested is likely due to an intracellular reduction of cystathionase protein.

Antigen-Antibody Complex↗
PubMed1981

High-dose nitrogen mustard (HN2) with autologous nonfrozen bone marrow transplantation in advanced malignant melanoma. A phase I trial.

In a Phase I trial patients with advanced malignant melanoma were treated with high-dose nitrogen mustard (HN2) and autologous bone marrow transplantation. Three patients were entered into the protocol. After procurement of 1.1--5.5 x 10(5) committed stem cells (CFU-C) per kg body wt, 33 mg/m2 of HN2 was administered i.v. as a bolus. Forty-eight hours later the noncryopreserved bone marrow was reinfused i.v. Side effects consisted of nausea, vomiting, anorexia, alopecia, phlebitis, hepatotoxicity, and neurotoxicity. Cardiotoxicity and hypocalcemia were encountered as unanticipated side effects not described so far by using lower dosages of HN2. Granulocytopenia of less than 10 x 10(9)/l and thrombocytopenia of less than 50.0 x 10(9)/l lasted for a mean of 10 and 8 days, respectively. Measureable disease present in two of three patients did not respond to the dose of HN2 used in this protocol. This study shows that hematologic recovery was shorter than previously reported in studies using HN2 without autologous bone marrow transplantation. The nonhematologic side effects of this dose of HN2, however, were severe and preclude the use of higher doses.

Adolescent↗
PubMed1981

Reduced gamma-cystathionase protein content in human malignant leukemia cell lines as measured by immunoassay with monoclonal antibody.

A murine hybrid cell line has been produced which secretes immunoglobulin G2b with specificity for human gamma-cystathionase (EC 4.2.1.15). The antibody has been iodinated and used in combination with quantitative immunoelectrophoresis in an assay which is capable of detecting as little as 1.5 ng enzyme protein. Human lymphoblastic leukemia cell lines CEM and Laz-221 contain undetectable enzyme protein, corresponding to their behavior as cysteine auxotrophs. In contrast, nonmalignant lymphoblastoid lines contain easily detectable enzyme protein which correlates with their behavior as cysteine prototrophs. Other malignant leukocyte cell lines contained detectable but variable amounts of enzyme protein, suggesting that the enzyme may be a useful marker of cellular differentiation.

Antibodies↗
PubMed1979

Defective prostaglandin synthesis by C3H/HeJ mouse macrophages stimulated with endotoxin preparations.

Macrophages obtained from C3H/HeN mice produced significant amounts of prostaglandin E when exposed to phenol-extracted lipopolysaccharides (LPS), whereas macrophages from C3H/HeJ mice were unresponsive. The lipid A fraction from phenol-extracted LPS was an effective inducer or prostaglandin synthesis by macrophages from C3H/HeN mice. The polysaccharide portion of the LPS molecule had no effect. In contrast, the C3H/HeJ macrophages did not produce prostaglandin E in response to the lipid A moiety of phenol-extracted LPS. LPS prepared by butanol extraction stimulated the production of prostaglandin E by macrophages from both C3H/HeN and C3H/HeJ mice. The component of butanol-extracted LPS that stimulated the C3H/HeJ macrophages was shown to be a lipid A-associated protein. Further studies demonstrated a correlation between prostaglandin production by the macrophages of these two strains of mice in response to butanol- and phenol-extracted LPS and the lethal effects of the endotoxin preparations.

Animals↗
PubMed1979

Dose limiting extramedullary toxicity of high dose chemotherapy.

Autologous marrow support may allow higher doses of myelosuppressive chemotherapy administration with the hope of improving tumor responses. The approach will be limited by the extramedullary toxicities of the drugs employed. This paper reviews some of these toxicities for selected drugs, and gives examples of techniques which could be used to reduce their incidence.

Antineoplastic Agents↗
PubMed1979

Lack of responsiveness of C3H/HeJ macrophages to lipopolysaccharide: the cellular basis of LPS-stimulated metabolism.

The rate of glucose utilization has been used as a measure of LPS-induced activation of cultures of C3H/HeN and C3H/HeJ spleen cells, peritoneal cells, and purified peritoneal adherent cells. Peritoneal cells utilized 40 to 60 times more glucose than did spleen cells and purified adherent monolayers were more active than mixed peritoneal cells, suggesting that only macrophage metabolism was being measured. The cell preparations for C3H/HeJ mice were not activated by Escherichia coli K235 LPS prepared by extensive phenol extraction, whereas C3H/HeN cells were activated by the LPS. Cells from both strains were activated by a commercially obtained E. coli 0111:B4 LPS and butanol-extracted K235 LPS. The addition of 10% C3H/HeN spleen cells to C3H/HeJ peritoneal cells resulted in a marked enhancement of glucose utilization. These findings suggest that LPS-induced enhancement of macrophage metabolism occurs both by direct action of LPS on macrophages as well as indirectly through activated lymphocytes.

Animals↗