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Biomedical subjects

J J Olson

Publications and source records attributed to J J Olson.

At least 37 records · Page 2Linked to original sources
PubMed1995

Reliability of differential PCR for the detection of EGFR and MDM2 gene amplification in DNA extracted from FFPE glioma tissue.

A series of 43 human gliomas, consisting of 30 glioblastomas, 7 anaplastic astrocytomas, 3 low grade astrocytomas, 2 ependymomas, and 1 oligodendroglioma, was studied for amplification of the epidermal growth factor receptor (EGFR) and mouse double minute 2 (MDM2) genes. DNA extracted from formalin-fixed, paraffin-embedded tissue sections was analyzed by differential PCR and the results were compared with slot blot examination of DNA extracted from frozen tissue from the same neoplasms. Twelve glioblastomas (40%) showed amplification of the EGFR gene, and overexpression of EGFR was evident in each of these tumors as indicated by the immunoperoxidase technique. Two of the tumors with EGFR gene amplification also revealed amplification of the MDM2 gene, while one additional glioblastoma revealed MDM2 amplification only. A 100% concordance in the detection of amplification was observed between differential PCR and slot blot analysis; consequently, these results indicate that differential PCR using DNA extracted from archival tissue sections is a reliable method of demonstrating gene amplifications in glial tumors.

Adult↗
PubMed1995

Analysis of epidermal growth factor receptor gene amplification and alteration in stereotactic biopsies of brain tumors.

In recent years, results from molecular-based investigations of central nervous system neoplasms have indicated that the occurrence of specific genetic alterations correlates with tumor malignancy and clinical behavior. One such example is epidermal growth factor receptor gene amplification and alteration in association with tumors histologically classified as glioblastoma multiforme. As our understanding of the implications of these changes develops, detection of epidermal growth factor receptor alteration and amplification may have diagnostic, prognostic, and ultimately, therapeutic value. The goal of this communication is to demonstrate the usefulness of stereotactic specimens for molecular genetic analysis, in this case, the analysis of the epidermal growth factor receptor gene for amplification and alterations. The techniques used here will maximize the number of cases from which useful information can be obtained. Properly adapted, the value of these techniques for expanding our understanding of these lesions is enormous.

Biopsy↗
PubMed1995

Isolation and culture of bovine intracranial arterial endothelial cells.

We report a simple explant technique to isolate and propagate endothelial cells from bovine cerebral arteries. The endothelial nature of the cells was confirmed by the presence of Factor VIII/von Willebrand antigen, the ability to phagocytize low-density lipoprotein, and the ability to be induced to express E-selectin. The lack of expression of the CD11c antigen and the absence of smooth muscle alpha-actin immunofluorescence suggested that the cultures were not contaminated with macrophages or smooth muscle cells, respectively. This technique yields pure cerebral arterial endothelial cell cultures, which will be of value for in vitro investigation of cerebrovascular physiology and disease processes.

Animals↗
PubMed1994

In vitro interaction of cisplatin and fosfomycin on squamous cell carcinoma cultures.

OBJECTIVE: Fosfomycin has been shown to be otoprotective and nephroprotective against cisplatin-induced toxic reactions. This study tests whether fosfomycin inhibits the anticancer effect of cisplatin. METHODS: Three squamous cell carcinoma cell lines were used to determine the effect of fosfomycin on cisplatin-induced tumoricidal activity. Cells were grown in 96 well plates with fosfomycin alone, cisplatin alone, or fosfomycin and cisplatin together. Cell survival was then measured by a colorimetric technique using 3-4,5-dimethylthiazol-2-yl 2,5 diphenyltetrazolium bromide (MTT). RESULTS: There was no decrease in the effectiveness of cisplatin in killing human squamous cell carcinoma in vitro when fosfomycin was present in concentrations of up to 400 mg/L. One cell line also showed killing at high concentrations of cisplatin, but not at low concentrations. CONCLUSIONS: Fosfomycin protects against cisplatin-induced toxic reactions and does not inhibit tumoricidal activity in vitro. In addition, one cell line showed relative resistance to cisplatin at low doses, but was effectively killed with high doses of cisplatin. This is the ideal situation for use of fosfomycin so that higher doses of cisplatin may be given with renal and otologic protection.

Carcinoma, Squamous Cell↗
PubMed1994

Laboratory evidence for the hormonal dependency of meningiomas.

Evidence for the hormonal dependency of meningiomas and of the value of various forms of endocrine therapy are described. Clinical features of the tumour are described. Laboratory evidence for the presence and activity of functional steroid receptors is described, and their characteristics are analysed. The effect of receptor antagonists on the growth of the tumour cells is indicated.

Combined Modality Therapy↗
PubMed1994

The efficacy and distribution of suramin in the treatment of the 9L gliosarcoma.

Suramin inhibits the stimulation of brain tumor deoxyribonucleic acid synthesis in vitro at concentrations of 200 to 400 mg/ml. This report evaluates suramin in the rodent 9L tumor model. Survival was analyzed by treating 10 tumor-bearing animals with suramin (7 mg/kg/d intraperitoneally) for 7 days, beginning 1 week after implantation, and compared with 20 untreated animals. Tissue distribution was analyzed with reverse-phase high-pressure liquid chromatography in homogenized organs of normal animals. Tumor concentration was measured over time in animals treated with a range of suramin doses, beginning 2 weeks after implantation. Suramin imparted no benefit as tumor-bearing control animals and treated animals survived 24.7 +/- 3.4 days and 24.5 +/- 1.5 days, respectively. In the animals receiving 7 mg/kg/d, renal concentrations of suramin were highest--339.8 +/- 30.9 mg/g as late as 25 days after treatment. Concentration in the brain peaked at only 3.3 +/- 1.3 mg/g after 10 days. Concentration in the tumor peaked at 74.4 +/- 16.5 mg/g the day of the last injection, significantly less than estimated by in vitro studies of efficacy. After injections of 35 mg/kg/d, tumor levels reached 230.9 +/- 139.2 mg/g with no evidence of inhibition of tumor progression. The response to a 7 mg/kg direct brain inoculation of suramin was assessed and compared with saline as a control. Animals treated with suramin died after 1 to 3 hours. Intracerebral hematoma volume at the injection site was 13.9 +/- 10.7 mm3 and 1.9 +/- 3.32 mm3 in the suramin-treated and control animals, respectively (P = 0.02), confirming the reported anticoagulant activity of suramin. Suramin is without efficacy in the 9L model because of poor systemic delivery. Alternative direct inoculation results in lethal local hemorrhage. Further consideration is necessary before the broad clinical application of this drug.

Animals↗
PubMed1994

Functional characterization of an EGF receptor with a truncated extracellular domain expressed in glioblastomas with EGFR gene amplification.

The most common type of alteration of the epidermal growth factor receptor gene (EGFR) in human glioblastomas results in the synthesis of an aberrant mRNA lacking 801 bases that encode amino acids 6-273 of the receptor's extracellular domain. To study the effects of this mutation on receptor function, we have developed chinese hamster ovary cell transfectants which express the mutant EGF receptor. Comparison of wild-type and mutant receptor properties in this cell host indicates that the truncated receptor does not bind EGF or TGF-alpha and, consequently, DNA synthesis is not stimulated in cultures of mutant transfectants by either grown factor. However, levels of DNA synthesis determined for mutant transfectants in serum-free media are several-fold higher than those determined for corresponding cultures of wild-type transfectants. Western blot analysis with anti-phosphotyrosine antibody indicates that the mutant receptor is constitutively phosphorylated in CHO cells, and the same analysis applied to lysates of glioblastoma biopsies reveals the altered receptor is readily detectable as a phosphotyrosine protein in tumors for which there is evidence of corresponding EGFR gene and transcript alterations. In total, these results indicate that the aberrant EGF receptor synthesized in glioblastomas, and which lacks a portion of the extracellular domain necessary for ligand binding, is an activated tyrosine kinase.

Animals↗
PubMed1993

Composite grafting for eyelid reconstruction.

Viable composite grafting is a technique used in eyelid reconstruction in which the graft is obtained from the contralateral eyelid. We reviewed the charts of 51 patients who underwent composite grafting of the eyelid since 1983. The average horizontal length of the defect repaired with this technique was 17.3 mm, and the most common indication for its use was basal cell carcinoma. Postoperatively, 39 (91%) of the 43 patients with available measurements had within 2.0 mm of palpebral fissure symmetry. Furthermore, this method of reconstruction allows survival of the eyelid margin and eyelid margin cilia. Composite grafting of the eyelid is a valuable method for eyelid reconstruction that provides acceptable cosmetic results.

Adolescent↗
PubMed1993

Basic fibroblastic growth factor as a potential meningeal angiogenic factor.

Vascular supply plays a significant role in the management of skull base tumors. The diagnosis is aided by contrast-enhanced imaging and angiographic techniques, and embolization procedures are used to devascularize certain lesions. The degree of surgical technical difficulty is strongly influenced by the degree of tumor vascularity. Although the importance of this blood supply is clearly understood, the mechanism involved in developing a system of tumor-perfusing vessels is yet to be defined. The development of a vascular network, or angiogenesis, is an important event in allowing tumor proliferation to progress beyond small clusters of cells. Basic fibroblastic growth factor (bFGF) is an especially attractive candidate as an angiogenic growth factor because of its ability to stimulate processes that are characteristic of angiogenesis in vitro. Tumors that involve the meninges may have the ability to liberate normally stored bFGF, which may, in turn, induce new vessel formation for continued tumor proliferation. An immunohistochemical analysis of rodent and bovine meninges to study this phenomenon is described. The dura, arachnoid, and their associated vessels are shown clearly to contain this growth factor. Ultimately, an adjuvant therapy based on the inhibition of angiogenesis may provide a reasonable alternative to aggressive surgical approaches in skull base tumors that are incompletely resectable.

Journal Article↗
PubMed1993

Acquired blepharoptosis secondary to essential blepharospasm.

We treated four patients with essential blepharospasm, receiving botulinum A toxin, in whom, although they had no preexisting blepharoptosis, a concurrent bilateral acquired blepharoptosis developed. Since the blepharoptosis did not improve after the period of time during which the effects of botulinum A toxin would have been expected to resolve (2 to 10 weeks), we judged that its development was unrelated to the toxin. We propose, rather, that the stretching, attenuation, disinsertion, or dehiscence of the upper eyelid levator muscle caused by the blepharospasm were at least partly responsible for the onset of the blepharoptosis. To ensure appropriate treatment in these cases, careful clinical evaluation is required to differentiate the two conditions.

Aged↗
PubMed1992

Suramin inhibits growth factor binding and proliferation by urothelial carcinoma cell cultures.

Suramin is a polyanionic compound recently noted to inhibit growth factor action and proliferation of several types of neoplastic cells in vitro. Data from clinical trials show antineoplastic activity against some prostatic and adrenal cortical carcinomas. Suramin is excreted unmetabolized into the urine suggesting possible application in treatment of urothelial carcinoma and prompting us to examine the drug's effect on growth factor binding and cell proliferation by two urothelial carcinoma cell lines. Half-maximal inhibition of 125I-epidermal growth factor (EGF) binding to T24 and HT1376 cells was produced by suramin concentration of approximately 300 and 100 microM, respectively. The corresponding value for 125I-insulin-like growth factor 1 (IGF1) binding was 60 microM for both cell lines. Inhibition of T24 and HT1376 growth was virtually complete at suramin concentrations in the range achievable clinically.

Animals↗
PubMed1992

Bilateral dacryocystitis after punctal occlusion with thermal cautery.

A 61-year-old woman developed acute bilateral dacryocystitis secondary to Staphylococcus aureus 3 weeks after undergoing punctal occlusion with thermal cautery for keratoconjunctivitis sicca. The dacryocystitis resolved with intravenous antibiotics, aspiration of the lacrimal sacs, injection of sulfacetamide into the lacrimal sacs, and bilateral dacryocystorhinostomy. Preexisting bilateral nasolacrimal duct obstruction was postulated as the underlying cause. In these cases, irrigation of the lacrimal system is recommended before proceeding with punctal occlusion.

Anti-Bacterial Agents↗
PubMed1992

Conventional frozen sections in periocular basal-cell carcinoma: a review of 236 cases.

Two hundred thirty-six periocular basal-cell carcinomas were resected under conventional frozen-section control. Only two tumors recurred, yielding a success rate of 99.2%. The mean follow up was 56 months. Eighty-one of the 236 patients were followed for at least 5 years; the 5-year cure rate was 97.5%. To our knowledge, this is the largest reported series of periocular basal-cell carcinoma resected under conventional frozen-section control; also, we believe the follow-up data are superior to those of previous series. The high success rates with conventional frozen-section techniques in this and other series are comparable to those reported for the Mohs micrographic techniques.

Adult↗
PubMed1992

The cerebral radioprotective effect of alternative barbiturates to pentobarbital.

The potential for normal brain tissue injury is one of the limiting factors in the use of radiotherapy for brain tumors. As attempts to enhance brain tumor radiation sensitivity have been unsuccessful, the use of cerebral radioprotectants provides an attractive alternative. Pentobarbital has recently been shown to be a cerebral radioprotectant in the rodent and primate models of single fraction radiation injury. Because daily high doses of pentobarbital bring certain significant risks, the potential usefulness of alternative barbiturates was explored. Seven groups of rats received 70 Gy of whole-brain-only irradiation in the single fraction. Group 1 was treated while awake. Groups 2, 3, and 4 received pentobarbital, thiopental, and methohexital, respectively. Groups 5, 6, and 7 received increasing doses of phenobarbital. Mean group survival at 30 days after treatment was determined and compared with the survival of animals treated while awake. Thiopental enhanced survival, similar to pentobarbital. Methohexital and phenobarbital were of no radioprotective value. The differences in the hypnotic effects of these barbiturates is based on dissimilar effects on the kinetics of chloride ion channel patency. We propose that these differences also influence their radioprotective properties. Thiopental is a shorter acting alternative to pentobarbital for cerebral radioprotection. Use of it should permit safer and easier investigation of this radioprotective effect in human trials.

Animals↗
PubMed1990

Reduction in radiation-induced brain injury by use of pentobarbital or lidocaine protection.

To determine if barbiturates would protect brain at high doses of radiation, survival rates in rats that received whole-brain x-irradiation during pentobarbital- or lidocaine-induced anesthesia were compared with those of control animals that received no medication and of animals anesthetized with ketamine. The animals were shielded so that respiratory and digestive tissues would not be damaged by the radiation. Survival rates in rats that received whole-brain irradiation as a single 7500-rad dose under pentobarbital- or lidocaine-induced anesthesia was increased from between from 0% and 20% to between 45% and 69% over the 40 days of observation compared with the other two groups (p less than 0.007). Ketamine anesthesia provided no protection. There were no notable differential effects upon non-neural tissues, suggesting that pentobarbital afforded protection through modulation of ambient neural activity during radiation exposure. Neural suppression during high-dose cranial irradiation protects brain from acute and early delayed radiation injury. Further development and application of this knowledge may reduce the incidence of radiation toxicity of the central nervous system (CNS) and may permit the safe use of otherwise "unsafe" doses of radiation in patients with CNS neoplasms.

Animals↗
PubMed1990

Enhancement of the efficacy of x-irradiation by pentobarbital in a rodent brain-tumor model.

Radiation therapy is an important component of brain tumor treatment, but its efficacy is limited by its toxicity to the surrounding normal tissue. Pentobarbital acts as a cerebral radioprotectant, but the selectivity of its protection for the central nervous system has not been demonstrated. To determine if pentobarbital also protects tumor against ionizing radiation, five groups of Fischer 344 rats were observed after exposure to varying combinations of the presence or absence of implanted tumor, pentobarbital, and radiation treatment. The first three groups underwent cerebral implantations of a suspension of 9L gliosarcoma cells. Group 1 was left untreated and served as tumor-bearing controls. Group 2 received 30 Gy of whole-brain x-irradiation without anesthesia 8 days after tumor implantation. Group 3 received the same radiation treatment 15 minutes after pretreatment with 60 mg/kg of pentobarbital intraperitoneally. Groups 4 and 5 served as radiation controls, receiving 30 Gy of x-irradiation while awake and 30 Gy of x-irradiation after pentobarbital administration, respectively. Survival was calculated from the death of the last tumor-bearing rat. The mean survival time in tumor-bearing control rats was 20.8 +/- 2.6 days (+/- standard deviation). X-irradiation alone significantly enhanced the period of survival in rats implanted with the 9L tumor (29.7 +/- 5.6 days, p less than 0.03). Further significant prolongation of survival was seen with the addition of pentobarbital to the treatment regimen (39.9 +/- 13.5 days, p less than 0.01). Nontumor-bearing rats irradiated while awake (Group 4) survived 30.9 +/- 2.3 days. All of their pentobarbital-anesthetized counterparts in Group 5 survived. If pentobarbital had offered radioprotection to the tumor, then Group 3 would have had a shorter survival period than Group 2. This implies that the enhancement of survival time after irradiation results from selective protection of normal brain in this model.

Animals↗
PubMed1990

Cerebral radioprotection by pentobarbital: dose-response characteristics and association with GABA agonist activity.

Pentobarbital reduces cerebral radiation toxicity; however, the mechanism of this phenomenon remains unknown. As an anesthetic and depressant of cerebral metabolism, pentobarbital induces its effects on the central nervous system by stimulating the binding of gamma-aminobutyric acid (GABA) to its receptor and by inhibiting postsynaptic excitatory amino acid activity. The purpose of this study is to investigate the role of these actions as well as other aspects of the radioprotective activity of pentobarbital. Fischer 344 rats were separated into multiple groups and underwent two dose-response evaluations. In one set of experiments to examine the relationship of radioprotection to pentobarbital dose, a range of pentobarbital doses (0 to 75 mg/kg) were given intraperitoneally prior to a constant-level radiation dose (70 Gy). In a second series of experiments to determine the dose-response relationship of radiation protection to radiation dose, a range of radiation doses (10 to 90 Gy) were given with a single pentobarbital dose (60 mg/kg intraperitoneally). Further groups of animals were used to evaluate the importance of the timing of pentobarbital administration, the function of the (+) and (-) isomers of pentobarbital, and the role of an alternative GABA agonist (diazepam). In addition, the potential protective effects of alternative methods of anesthesia (ketamine) and induction of cerebral hypometabolism (hypothermia) were examined. Enhancement of survival time from acute radiation injury due to high-dose single-fraction whole-brain irradiation was maximal with 60 mg/kg of pentobarbital, and occurred over the range of all doses examined between 30 to 90 Gy. Protection was seen only in animals that received the pentobarbital before irradiation. Administration of other compounds that enhance GABA binding (Saffan and diazepam) also significantly enhanced survival time. Ketamine and hypothermia were without protective effect. Protection from acute radiation-induced mortality by pentobarbital in the rat model is a reproducible phenomenon and is associated with the GABA agonistic activity of the compound. This property of GABA agonists offers the potential for a novel approach to enhancement of the efficacy of radiation therapy in the treatment of brain tumors.

Anesthesia, General↗