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Biomedical subjects

J Emrich

Publications and source records attributed to J Emrich.

At least 19 recordsLinked to original sources

Radiation safety education for laboratory animal science.

Students enrolled in the laboratory animal science graduate program at MCP Hahnemann University seek to gain entrance to veterinary school or to manage an animal facility within an academic institution, pharmaceutical or biotechnology company conducting biomedical research. Ongoing interaction between faculty in the radiation oncology, radiation safety, and lab animal science disciplines revealed an acute need for radiation safety education for laboratory animal science students who will likely interact with researchers either designing and writing protocols for animal studies using radiation or radioactive materials, or veterinary staff who will use sources of radiation to diagnose and/or treat possible animal injuries and diseases. A core course in the Radiation Sciences graduate program was modified to address the needs of these students, instructing them in radiation safety, detection and counting instrumentation, and radiation biology. These fundamental areas were integrated to help the students gain a sound, basic knowledge of radiation and radioactive materials used in biomedical research.

Animals↗

Identification of fatty acid methyl esters (FAMEs) in postmortem tissue. A new marker of alcohol abuse?

Based on a method that combines thin layer chromatography and gas chromatography, it proved possible to detect postmortem fatty acid methyl esters (FAMEs) in human tissues (pancreas, liver, heart and adipose tissue). The highest concentrations were found in the pancreas, medium concentrations in the liver and adipose tissue and the lowest concentration in heart tissue. All tissues contained higher concentrations of unsaturated FAMEs than saturated FAMEs. In order to evaluate the influence of alcohol consumption on the formation of FAMEs, the decreased were divided into three groups: control group, chronic alcoholics (who were alcohol free at the time of death), and acutely alcohol-intoxicated subjects (so intoxicated at the time of death with no evidence of chronic alcohol abuse). In comparison to the control group, the organs of the chronic alcoholics showed only slight values, the tissues of the acutely intoxicated subjects were obviously higher. Based on the varying concentration distribution in the three groups, it seemed that postmortem differentiation of the alcohol consumption which existed before the time of death would be possible. After further investigation with a greater number of samples, FAMEs could become a useful supplement to existing alcohol markers in the future.

Adipose Tissue↗

Epidermal growth factor receptor 425 monoclonal antibodies radiolabeled with iodine-125 in the adjuvant treatment of high-grade astrocytomas.

Fifty-nine patients with primary presentation of high-grade gliomas of the brain, 13 with astrocytomas with anaplastic foci and 46 with glioblastoma multiforme, were treated with surgical intervention and definitive postoperative radiation therapy followed by multiple intravenous administration of iodine-125-labeled monoclonal antibody-425, which binds specifically to human epidermal growth factor receptor. The total cumulative labeled antibody doses ranged from 40 to 296 mCi. The administration of the radiolabeled antibody was performed in most instances within 3 months following completion of the primary surgery and radiation therapy. No significant life-threatening toxicities were observed during the trial. At one year, 34 (58%) of the 59 patients in the trial were alive. The median overall survival for both groups was 13.5 months.

Adjuvants, Immunologic↗

Malignant astrocytomas treated with iodine-125 labeled monoclonal antibody 425 against epidermal growth factor receptor: a phase II trial.

Twenty-five patients with primary presentation of malignant astrocytoma, astrocytoma with anaplastic foci, and glioblastoma multiforme were treated with surgical resection and definitive radiation therapy followed by intravenous or intra-arterial administration of Iodine-125 labeled monoclonal antibody-425, which binds specifically to human epidermal growth factor receptor. The patients presented with primary untreated disease, positive contrast enhanced computed tomography scans of the brain, and compatible clinical symptoms. In this Phase II clinical trial, the patients had surgical debulking or biopsy followed by definitively administered external beam radiation therapy and one or multiple doses (35 to 90 mCi per infusion) of radiolabeled antibody. The total cumulative doses ranged from 40 to 224 mCi. The administrations of the radiolabeled antibody were performed in most cases 4-6 weeks following completion of the primary surgery and radiation therapy. Ten patients had astrocytoma with anaplastic foci and 15 had glioblastoma multiforme. No significant life-threatening toxicities were observed during this trial. At 1 year 60% of the patients with astrocytoma with anaplastic foci or glioblastoma multiforme are alive. The median survival for both groups was 15.6 months.

Actuarial Analysis↗

Early metabolic changes following chemotherapy of human gliomas in vivo demonstrated by phosphorus magnetic resonance spectroscopy.

The authors have used phosphorus magnetic resonance spectroscopy to monitor pH changes in malignant gliomas following treatment with intravenous and intra-arterial 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU). Image-guided, localized phosphorus spectra of human gliomas in situ were obtained using a 1.5-T whole body combined imaging and spectroscopy system. Initial intravenous BCNU treatment was followed by a transient decrease of tumor intracellular pH by 0.15 +/- 0.03 pH units (mean +/- SD). Superselective intra-arterial administration of the same drug was followed by an increase of tumor intracellular pH by 0.15 +/- 0.6 pH units (mean +/- SD). These changes occurred prior to any changes on x-ray, computed tomography (CT), or magnetic resonance imaging (MRI). In addition to enhancing our understanding of the metabolic effects of BCNU, such changes may correlate with drug efficacy or toxicity and may be useful in guiding therapy in the future.

Astrocytoma↗

Superselective cerebral arterial infusion of BCNU in high-grade glioma: the radiologist's point of view.

Thirty-two patients suffering from high-grade glioma were candidates for superselective cerebral arterial infusion of 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU) after surgery and radiation therapy. There were 74 catheterizations using an 8-French guiding catheter through which a 2.5-French balloon catheter was placed into the main arterial trunk feeding the tumor. Eleven procedures were abandoned because of arterial spasm with a transient neurological deficit or because of prolonged catheterization time. Sixty-three infusions of BCNU were done, each lasting three hours. Eighty-one percent of patients showed stabilization or improvement on computed tomographic (CT) scans five weeks after treatment. We thus demonstrate the safety of supraophthalmic catheterization, the feasibility of prolonged catheterization, and the relative effectiveness of low doses of BCNU infused over a long period of time in the treatment of cerebral gliomas.

Brain Neoplasms↗

Delineation of a transplanted malignant melanoma with indium-111-labeled porphyrin.

An indium complex of a cationic, water-soluble, synthetic porphyrin, tetra-4-N-methylpyridyl porphyrin tosylate, has been prepared and evaluated for its selective localization in tumors in Syrian Golden hamsters with flank transplanted malignant melanoma (Fortner MMI). Tumor-to-blood ratios of the compound increase from 42:1 at 6 hr postinjection, at which time activity levels in the tumor exceed those in all other tissues, to 162.1 at 72 hr. Images in one hamster at three time periods clearly delineated the tumor from nontarget background and also demarcated the viable and necrotic zones within the tumor itself.

Animals↗

Synthesis and evaluation of an 111In-labeled porphyrin for lymph node imaging.

111In-labeled tetra(4-N-methylpyridyl)porphyrin was investigated as a possible lymph node imaging agent. A clinically feasible method for the preparation of this radioactive pharmaceutical was developed from experiments with the synthesis and characterization of the unlabeled complex. The in vivo distribution of the compound in Wistar rats was determined as a function of time. Favorable lymph node-blood, lymph node-muscle, and specific lymph node-surrounding tissue ratios were obtained.

Animals↗

The role of respiratory muscles in the hyperinflation of bronchial asthma.

To examine the mechanism of hyperinflation in bronchial asthma we studied lung and chest wall mechanics in 7 asymptomatic patients in whom progressive bronchoconstriction was induced by doubling the amount of inhaled aerosolized histamine. An increase in pulmonary resistance (RL) from 2.5 +/- 0.3 cmH2O . 1-1 . s (mean, +/- 1 SE) to 12.3 +/- 0.9 cmH2 was associated with a linear increase in functional residual capacity (FRC) up to 74.7 +/- 1.7% of control total lung capacity (TLCc). The mean regression coefficient was 2.3% TLCc . cmH2O-1 . 1 . s-1. At each level of hyperinflation the most positive expiratory pleural pressures measured during spontaneous breathing were generally less than the predicted chest wall relaxation pressures, indicating persistent inspiratory muscle contraction throughout expiration. This was predominantly due to inspiratory intercostal and accessory muscle activity, because measurements of transdiaphragmatic pressure indicated complete diaphragmatic relaxation early in expiration. Recruitment of abdominal muscles during expiration, inferred from measurements of gastric pressure (Pg) and abdominal antero-posterior (A-P) diameter, was progressively more apparent with increasing bronchoconstriction. We concluded that the increase in FRC in induced asthma is substantially influenced by persistent inspiratory intercostal and accessory muscle activity during expiration. Concomitant abdominal muscle recruitment results in a chest wall configuration that tends to optimize diaphragmatic function.

Abdomen↗

Tissue distribution and retention of 5-thio-D-glucose in animal tumor models.

5-Thio-D-glucose (5-TDG) has demonstrated potential as a radiation sensitizer for hypoxic cells growing in monolayer culture and as multicell spheroids. We have studied the biodistribution and pharmacokinetics of radiolabeled (35S or 3H) 5-TDG prior to utilizing this bioisotere of D-glucose for radiation sensitization studies in vivo. At all times after administration, 5-TDG achieved higher tissue levels of radioactivity in hamster pancreatic tumors of ductal and acinar cell origin than in the normal pancreas. By 2 hours after intravenous injection, the duct tumor activity concentration exceeded that of any other tissue; a similar situation obtained after 4 hours in the acinar tumor model. However, the functioning insulinoma model exhibited similar radioactivity uptake and kinetics as did normal pancreas. In all models, metastases behaved similarly to the primary transplanted tumor in terms of uptake and retention of radioactivity. Addition of carrier 5-TDG appeared to abrogate much of the selective uptake of label into tumor relative to normal tissue, in terms of % dose/g tissue, but the total uptake into tumor was greater. The drug is rapidly excreted in the urine and the nature of this excretion was examined. Retention of activity in normal lung tissue was similar to that of pancreatic tumors and prompted a study of uptake into Lewis lung carcinoma. Again, tumor uptake in % dose/g approximated uptake into normal lung tissue, but total uptake into tumor was greater. These studies provided the basis for initiation of in vivo studies of potential cytotoxic and radiation-potentiating activity of 5-TDG.

Adenocarcinoma↗

Voluntary changes in ventilation distribution in the lateral posture.

To determine whether voluntary changes in the pattern of inspiratory muscle contraction influence topographical distribution of ventilation in the lateral decubitus posture during tidal breathing, we studied 4 normal subjects who breathed either naturally (N) or preferentially with intercostal and accessory muscles (IC), or with enhanced motion of the diaphragm and abdomen (Ab). We performed N2 as well as 133Xe washouts (after equilibration) which were measured at the mouth while recording regional count rates by external scintillation detectors. Ventilation per unit volume (delta V/Vo) in the nondependent lung regions was 0.55 +/- 0.05 (mean +/- 1 SD) and 0.42 +/- 0.02 of that in the dependent regions during natural and sustained Ab breathing, respectively. In contrast, during IC breathing this ratio was 0.99 +/- 0.17. Although N2 washout curves obtained during IC breathing more closely approached a monoexponential than did those from N and Ab runs, a two compartment analysis of washouts at the mouth did not demonstrate significant differences between breathing patterns. We conclude that in the lateral posture voluntary relaxation of the diaphragm during tidal breathing distributes the gas preferentially to the nondependent lung regions. Conversely, during N and Ab breathing the preferential ventilation of dependent regions is due to contraction of the diaphragm.

Diaphragm↗

Biodistribution and pharmacokinetics of S-35-labeled 5-thio-D-glucose in hamsters bearing pancreatic tumors.

5-thio-D-glucose (5-TDG) exerts profound effects on rapidly metabolizing tissues. We have used liquid scintillation counting to study the tissue distribution and pharmacokinetics of S-35-labeled 5-TDG in hamster models of pancreatic tumors. In the normal hamster, initial uptake of S-35 activity into kidney, liver, and blood was high, but rapidly decreased with time. The pancreatic uptake (% dose/g) never exceeded 0.75%. This level occurred only at the earliest times after administration. Uptake in all three tumor models exceeded that in pancreatic tissue within 15 min of injection. The highest tumor-to-pancreas ratio was seen in the duct-tumor model, which also exhibited the most favorable tumor-to-tissue ratio when compared with kidney, liver and muscle. Favorable ratios were most pronounced at 6 and 24 hr after injection. These studies provide impetus for the use of 5-TDG as a model compound for the synthesis of potentially useful agents for clinical detection of pancreatic tumors.

Adenocarcinoma↗

Frame shift mutations near the beginning of the lysozyme gene of bacteriophage T4.

A pair of frame shift mutations in the lysozyme gene of bacteriophage T4 results in the substitution of a glutamyl-tyrosyl sequence for the asparagine residue that is the penultimate amino-terminal amino acid in the lysozyme of the wild-type strain. One of the mutations has been identified as the insertion of two bases, the other as the insertion of a single base.

Amino Acid Sequence↗