Biomedical subjects

M Arneson

Publications and source records attributed to M Arneson.

9 recordsLinked to original sources

PubMed1997

Effects of short-term in vivo administration of G-CSF on bone marrow prior to harvesting.

The brief administration of G-CSF to previously treated solid tumor patients has a positive impact on the overall cellularity and progenitor cell content of harvested bone marrow. Fifty-seven patients, fully recovered from therapy and growth factor support, had approximately 500 mL of steady-state marrow harvested as outpatients under local anesthesia. Each patient then received 5 micrograms/kg of G-CSF every 12 hours subcutaneously for either 24 hours (21 patients), 36 hours (20 patients), or 48 hours (16 patients) just before harvesting 500 mL of activated bone marrow. Bone marrow cellularity (x 10(6)/mL) increased from a steady-state mean of 10.7 (+/- 0.9) to 25.7 (+/- 2.8) after 24 hours, 9.3 (+/- 0.7) to 29 (+/- 2.5) after 36 hours, and 9.6 (+/- 0.7) to 28.4 (+/- 2.5) after 48 hours. Although the percentage of CD34+ cells did not significantly change in stimulated marrow, the total number of CD34+ cells (x 10(6)) collected increased from 34 (+/- 6.3) to 52 (+/- 6.6) after two injections, 28 (+/- 3.6) to 65 (+/- 8.5) after three injections, and 28 (+/- 5.4) to 75 (+/- 18) after four injections of G-CSF. Further phenotyping demonstrated significant increases in CD34+HLA-DR+ cells with all three schedules relative to steady-state marrow. There were no changes in the total number of CD34+HLA-DR- cells after two and four shots; however, this population increased from 10 x 10(6) in steady-state marrow to 23 x 10(6) (p = 0.012) after three injections. Analysis of peripheral blood indicated a statistically significant increase in the circulating white count, but more interestingly, there were significant increases in the number of CD34+ cells x 10(4)/mL, suggesting the onset of mobilization. Steady-state blood contained a mean of 0.86 x 10(4)/mL CD34+ cells, which increased to 4.37 x 10(4)/mL, 7.43 x 10(4)/mL, and 8.62 x 10(4)/mL after two, three, and four injections, respectively-levels of CD34+ cells that are comparable to steady-state marrow. Reinfusion of a median of 1.6 x 10(6) activated CD34+ cells/kg resulted in the recovery of > 100/mm3 neutrophils and > 20,000 platelets by days 9 and 19, respectively, which was faster than our previous patients who received steady-state marrow, and comparable to our patients who received mobilized peripheral stem cells.

Adult↗

PubMed1996

Phase I trial of an antisense oligonucleotide OL(1)p53 in hematologic malignancies.

PURPOSE: The phosphoprotein p53 is involved in transcriptional regulation and is detected in hematologic malignancies. In vitro incubation of acute myelogenous leukemia with OL(1)p53, a 20-mer phosphorothioate oligonucleotide complementary to p53 mRNA, results in leukemic cell death. A phase I dose-escalating trial was conducted to determine the toxicity of OL(1)p53 following systemic administration to patients with hematologic malignancies. PATIENTS AND METHODS: Sixteen patients with either refractory acute myelogenous leukemia (n = 6) or advanced myelodysplastic syndrome (n = 10) participated in the trial. Patients were given OL(1)p53 at doses of 0.05 to 0.25 mg/kg/h for 10 days by continuous intravenous infusion. RESULTS: No specific toxicity was directly related to the administration of OL(1)p53. One patient developed transient nonoliguric renal failure. One patient died of anthracycline-induced cardiac failure. Approximately 36% of the administered dose of OL(1)p53 was recovered intact in the urine. Plasma concentrations and area under the plasma concentration curves were linearly correlated with dose. Leukemic cell growth in vitro was inhibited as compared with pretreatment samples. There were no clinical complete responses. CONCLUSION: A phosphorothioate oligonucleotide, OL(1)p53, can be administered systemically without complications. This type of modified oligonucleotide can be administered without complete degradation, as it was recovered from the urine intact. This oligonucleotide may be useful in combination with currently available chemotherapy agents for the treatment of malignancies.

Adult↗

PubMed1995

A marrow harvest procedure under local anesthesia.

This report details a bone marrow harvest procedure performed outside the hospital setting under local anesthesia, thereby avoiding many of the risks associated with the traditional surgical procedure. In approximately 30 minutes, 450 milliliters of marrow can be collected from eight bone punctures, containing a median of 4.18 x 10(9) cells and 33 x 10(6) progenitor cells as defined by CD34 expression. Reinfusion of a median 1.2 x 10(6) CD34+ cells/kg in 10 breast cancer and lung cancer patients after dose-intensive chemotherapy resulted in the recovery of granulocytes > 100/mm3 by day 14 and platelets > 20,000 by day 21. Without progenitor cell support, such recoveries could take 30 and 40 days, respectively. Collection of marrow using this protocol does not compromise the engraftment capability of the progenitor cells, seldom necessitates blood product support, is safer for the patient, and reduces the cost of harvesting by 75% compared to inpatient or day surgery procedures.

Anesthesia, Local↗

PubMed1992

The distribution of the fiber cell intrinsic membrane proteins MP20 and connexin46 in the bovine lens.

MP20 is an intrinsic membrane protein previously identified in mammalian lens fiber cells. To identify a possible role for this protein in the lens, the distribution of MP20 and connexin46 has now been examined. Western immunoblotting with an anti-peptide antibody generated to the C-terminal 8 amino acids of MP20 confirmed the presence of this protein in the lens of several different mammalian species. A monoclonal antibody 5H1 was prepared that, in Western blots of bovine lesn membranes, recognized the same component as an antibody to rat connexin46 (Cx46). The apparent molecular mass of this component decreased from 59 kDa to 55 kDa following treatment of lens membranes with alkaline phosphatase. A monoclonal antibody to connexin-related MP70 recognized a 70 kDa component in bovine lens membranes confirming the presence of these two different connexin proteins in bovine lens membranes. To localize MP20 and Cx46 in the bovine lens membrane, lens fiber cell bundles were immunofluorescently labeled with both the MP20 antibody, and the monoclonal antibody to Cx46. Cx46 was identified in large plaques on the broad faces of the lens fiber cells throughout the outer 1 mm of the lens cortex. MP20 colocalized with Cx46 only in a restricted area 0.5 mm to 1.0 mm into the lens. In other regions of the lens, MP20 appeared more diffusely distributed over the fiber cell surface, although apparently concentrated in the ball-and-socket regions at the corners of the narrow side of the inner cortical lens fiber cells. These inner cortical regions were devoid of Cx46. A difference in distribution of these two proteins was confirmed in studies of immunofluorescently labeled lens cryosections. Furthermore, immunogold electron microscopy of purified lens membranes identified MP20 in both junctional regions (with Cx46) and in single membranes. These results provide evidence for a role for MP20 in mammalian lens fiber cell junctional formation or organization.

Animals↗

PubMed1991

Pulmonary surveillance using bronchoscopy and bronchoalveolar lavage during high-dose antineoplastic therapy.

Pulmonary failure is a major contributor to morbidity and mortality during marrow aplasia following high-dose antineoplastic therapy. For this reason, we initiated a pulmonary surveillance program for patients undergoing high-dose chemotherapy for leukemia or bone marrow transplantation. As part of this program, bronchoscopy with BAL was performed prior to therapy and at the onset of granulocytopenia. Thirty-three of the first 57 patients managed in this program developed some evidence of pulmonary complications. Twelve patients died in aplasia; all had pulmonary failure. Forty patients had clinically significant abnormalities on the bronchoscopy before treatment including 12 of 19 patients who had normal findings on chest x-ray films, physical examination, and pulmonary function testing, and no fever. Twenty-seven patients had clinically significant abnormal bronchoscopy or BAL at the onset of granulocytopenia. Thirteen patients required additional bronchoscopy. No patient required an open lung biopsy. Pulmonary surveillance using bronchoscopy with BAL is useful in the detection of pulmonary disease prior to the initiation of and following high-dose antineoplastic therapy.

Adult↗

PubMed1991

Diffuse pulmonary alveolar hemorrhage after bone marrow transplantation: radiographic findings in 39 patients.

Diffuse alveolar hemorrhage is a life-threatening complication after bone marrow transplantation. We investigated the radiographic abnormalities that occurred in 39 transplantation patients with a diagnosis of diffuse alveolar hemorrhage and correlated the findings with the patients' clinical course. The initial radiographic abnormalities after diffuse alveolar hemorrhage developed an average of 11 days after bone marrow transplantation, and the radiographic abnormalities preceded the clinical diagnosis by an average of 3 days. Twenty-seven patients initially had bilateral radiographic abnormalities; 10 initially had unilateral abnormalities (seven in the right lung, three in the left lung). Two patients had normal chest radiographs throughout their clinical course. All 37 patients with radiographic abnormalities had abnormalities involving the central portion of the lung, primarily the middle and lower lung zones. The initial radiographic pattern was interstitial in 27 and alveolar in 10. In 24 patients, radiographic abnormalities were initially judged to be mild; three were severe from the onset. Radiographic abnormalities rapidly worsened in most patients over 6 days. In 30 patients, diffuse bilateral radiographic abnormalities involving all lung zones developed. Eleven patients persisted in having only interstitial radiographic abnormalities; 26 had a confluent alveolar pattern. At the height of radiographic abnormalities, 27 cases were judged to be severe, and only one case was judged to be mild. The mortality rate in patients with diffuse alveolar hemorrhage was 77%. The radiographic abnormalities of diffuse alveolar hemorrhage are nonspecific and usually precede the clinical diagnosis. The clinical course after hemorrhage is short, often resulting in death.

Adolescent↗

PubMed1989

Structural organization of the lens fiber cell plasma membrane protein MP18.

The 18,000-dalton bovine lens fiber cell intrinsic membrane protein MP18 was phosphorylated on a serine residue by both cAMP-dependent protein kinase and protein kinase C. In addition, this protein bound calmodulin and was recognized by a monoclonal antibody (2D10). These different regions were localized using enzymatic and chemical fragmentation of electrophoretically purified MP18 that had been phosphorylated with either cAMP-dependent protein kinase or protein kinase C. Partial digestion of 32P-labeled MP18 with protease V8 resulted in a Mr = 17,000 peptide that bound calmodulin, but neither contained 32P or was recognized by the monoclonal antibody 2D10. Furthermore, the 17-kDa peptide had the same N-terminal amino acid sequence as MP18. Thus, the monoclonal antibody 2D10 recognition site and the protein kinase phosphorylation site(s) are close together and confined to a small region in the C terminus of MP18. This conclusion was confirmed in experiments where MP18 was fragmented with trypsin, endoproteinase Lys-C, or CNBr. The location of the phosphorylation site was confirmed by sequencing the small 32P-labeled, C-terminal peptide that resulted from protease V8 digestion of 32P-labeled MP18. This peptide contained a consensus sequence for cAMP-dependent protein kinase.

Amino Acid Sequence↗

PubMed1989

Diffuse alveolar hemorrhage in autologous bone marrow transplant recipients.

PURPOSE: The purpose of our work was to evaluate pulmonary complications in autologous bone marrow transplant recipients. PATIENTS AND METHODS: A total of 141 consecutive autologous bone marrow transplant recipients were evaluated. In 29 patients, a clinical syndrome characterized by progressive dyspnea, hypoxia, cough, diffuse consolidation on chest roentgenography, and characteristic bronchoalveolar lavage findings developed over one to seven days. RESULTS: In 29 patients, bronchoalveolar lavage performed by sequential instillation and aspiration of 20-ml aliquots of normal saline resulted in recovered lavage fluid that became progressively bloodier with each recovered aliquot. Autopsy and bronchoalveolar lavage in these patients revealed no pathogens that accounted for the clinical findings. Since the later aliquots sample predominantly alveolar material, this syndrome was termed diffuse alveolar hemorrhage (DAH). DAH was associated with a high inpatient mortality rate (23 of 29 died versus 14 of 112 without DAH, p less than 0.001) and was associated with age over 40 years, solid malignancies, high fevers, severe mucositis, white blood cell recovery, and renal insufficiency (p less than 0.05, compared with patients without DAH). However, DAH was not associated with prolonged prothrombin or partial thromboplastin times or decreased platelet counts compared with patients without DAH. CONCLUSION: DAH is a frequent cause of respiratory compromise and a major cause of mortality in autologous bone marrow transplant recipients.

Adult↗

PubMedDate not supplied

The Hippocratic Oath.

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Ethics, Medical↗