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Biomedical subjects

J Bertram

Publications and source records attributed to J Bertram.

At least 37 records · Page 2Linked to original sources
PubMed1994

Reduction of erbB2 gene product in mamma carcinoma cell lines by erbB2 mRNA-specific and tyrosine kinase consensus phosphorothioate antisense oligonucleotides.

A considerable reduction of up to 75% at the protein level of the erbB2 gene product was observed using phosphorothioate antisense oligonucleotides directed against specific sequences of the erbB2 mRNA. Antisense oligonucleotides used were the 14-mer (translation start region) and the 17-mer (3' translated region) all-phosphorothioate oligonucleotides (S-ODNs). Sense or random sequences were used as a control. The greatest reduction at the erbB2 protein level was obtained after a 24h incubation with a single dose of 2 microM antisense S-ODN. The erbB2-mRNA-specific and the tyrosine kinase consensus antisense S-ODNs were comparably effective in inhibiting erbB2 expression. Addition of the transfection reagent DOTAP diminished the efficiency of erbB2 protein reduction by antisense S-ODNs after an incubation period of 24h but was more effective after 48h compared to the application of antisense S-ODNs alone.

Base Sequence↗
PubMed1992

Isopropylbenzene (cumene)--a new substrate for the isolation of trichloroethene-degrading bacteria.

Various bacterial isolates from enrichments with isopropylbenzene (cumene), toluene or phenol as carbon and energy sources were tested as to their potential to oxidize trichloroethene (TCE). In contrast to toluene and phenol, all isolates enriched on isopropylbenzene were able to oxidize TCE. Two isolates, strain JR1 and strain BD1, were identified as Pseudomonas spec. and as Rhodococcus erythropolis, respectively. TCE oxidation was accompanied by the liberation of stoichiometric amounts of chloride. Initial TCE oxidation rate increased proportional to the substrate concentration from 25 to 200 microM TCE. Maximal initial TCE-degradation rates found here were 4 to 5 nmol.min-1.mg protein-1. The TCE degradation rate decreased with time. The two isolates showed a temperature optimum for TCE degradation between 10 and 20 degrees C. In addition to TCE, R. erythropolis BD1 degraded only cis- and trans-dichloroethene whereas Pseudomonas spec. JR1 was able to oxidize also 1,1-dichloroethene, vinyl chloride, trichloroethane, and 1,2-dichloroethane.

Benzene Derivatives↗
PubMed1991

Minimal toxicity during protein A immunoadsorption treatment of malignant disease: an outpatient therapy.

Extracorporeal removal or modulation of circulating immune complexes (CIC) from plasma of animals and humans with malignant disease may be associated with induction of immune-mediated anti-tumor responses. Immunoadsorption columns containing heat-killed and formalin-fixed Staphylococcus aureus or staphylococcal protein A have been used for this purpose but treatments have often been associated with cardiopulmonary toxicity. Recently, an immunoadsorption device containing highly purified protein A covalently attached to a silica matrix (PROSORBA column) was used to treat 142 patients with refractory malignancies and 22 of 104 patients evaluated for anti-tumor response had objectively measurable reduction in tumor burden. In contrast to earlier experience with other devices, the procedures used in this trial were well tolerated and could be performed on an outpatient basis. The most common side effects observed among 1,306 treatments were chills (28% of treatments), low grade fever (28%), and musculoskeletal pain (16%). Side effects were mild to moderate and required no treatment or only symptomatic treatment. Treatment schedules were interrupted due to side effects for only six patients and there were no treatment-related deaths. Of 64 patients available for long-term follow-up evaluation (mean of 11 months), none exhibited evidence of long-term treatment-related side effects. None of the patient deaths in that period were associated with short or long-term treatment-related side effects. Protein A-silica (PROSORBA columns) can be used safely for development of further experimental treatments of malignant disease.

Adolescent↗
PubMed1991

Natural transfer of conjugative transposon Tn916 between gram-positive and gram-negative bacteria.

The conjugative streptococcal transposon Tn916 was found to transfer naturally between a variety of gram-positive and gram-negative eubacteria. Enterococcus faecalis hosting the transposon could serve as a donor for Alcaligenes eutrophus, Citrobacter freundii, and Escherichia coli at frequencies of 10(-6) to 10(-8). No transfer was observed with several phototrophic species. Mating of an E. coli strain carrying Tn916 yielded transconjugants with Bacillus subtilis, Clostridium acetobutylicum, Enterococcus faecalis, and Streptococcus lactis subsp. diacetylactis at frequencies of 10(-4) to 10(-6). Acetobacterium woodii was the only gram-positive organism tested that did not accept the transposon from a gram-negative donor. The results prove the ability of conjugative transposable elements such as Tn916 for natural cross-species gene transfer, thus potentially contributing to bacterial evolution.

Bacillus subtilis↗
PubMed1989

Noninvasive monitoring of drug biodistribution and metabolism: studies with intraarterial Pt-195m-cisplatin in humans.

We have performed a comparative evaluation of systemic (i.v.) and intraarterial (i.a.) cisplatin by using a trace dose of the radiolabeled form of this drug [( 195mPt]cisplatin) to monitor the drug's biodistribution by dynamic scintigraphic imaging. We have analyzed the drug's metabolism using a compartmental model both following i.a. and i.v. administration in patients with gliomas. Significantly larger amounts of radioactivity (up to 10 times higher than in the uninvolved brain) were measured in tumors following i.a. administration, whereas the differential localization following i.v. drug administration was, at best, only twofold that of the uninvolved brain. On the other hand, no significant differences could be detected in the pharmacokinetics of either free cisplatin or platinated proteins in blood. The washout slope in tumors following i.a. administration may be an indicator of the higher local concentration of free cisplatin; no such washout could be observed in tumors following i.v. administration. The present noninvasive methods may help document the amount and the rate of (active) drug deposition at the desired target site. They may also assist in monitoring, prospectively and/or, on line, the probable effect of chemotherapy in an individual patient. In turn it may lead to novel methods for optimizing chemotherapeutic effectiveness at specific tumor-bearing sites and in defined treatment protocols.

Cisplatin↗
PubMed1989

Purification and characterization of the pyruvate-ferredoxin oxidoreductase from Clostridium acetobutylicum.

The pyruvate-ferredoxin oxidoreductase from Clostridium acetobutylicum was purified to homogeneity and partially characterized. A 9.2-fold purification was achieved in a three step purification procedure: ammonium sulfate fractionation, chromatography on Phenyl Sepharose and on Procion Blue H-EGN12. The pure enzyme exhibited a specific activity of 25 U/mg of protein. Homogeneity of the pyruvate-ferredoxin oxidoreductase was confirmed by native polyacrylamide gel electrophoresis and sodium dodecylsulfate (SDS)-polyacrylamide gel electrophoresis. The molecular weight was determined to be 123,000/monomer. The subunit composition of the native enzyme could not be determined because of the instability of the pure enzyme. The pyruvate-ferredoxin oxidoreductase is sensitive to oxygen and dilution during purification. The dilution inactivation could be partially overcome by the addition of 300 microM coenzyme A or 50% ethyleneglycol. A thiamine pyrophosphate content of 0.39 mol per mol of enzyme monomer was found, the iron and sulfur content was 4.23 and 0.91, respectively. The pH-optimum was at pH 7.5 and the temperature optimum was at 60 degrees C. Kinetic constants were measured in the forward reaction. The apparent Km for pyruvate and coenzyme A were 322 microM and 3.7 microM, respectively. With 2-ketobutyrate the pyruvate-ferredoxin oxidoreductase showed 12.5% of the activity compared to pyruvate. No activity was found with 2-ketoglutarate. Ferredoxin from Clostridium pasteurianum could be used as physiological electron acceptor.

Chromatography, Ion Exchange↗
PubMed1989

Treatment of patients with HIV thrombocytopenia and hemolytic uremic syndrome with protein A (Prosorba column) immunoadsorption.

Both antibodies and circulating immune complexes (CIC), which bind to platelets and induce the destruction and clearance of platelets by the reticuloendothelial system, are found in patients with human immunodeficiency virus (HIV) and immune thrombocytopenic purpura (ITP). IgG and CIC were removed from patients' plasma by extracorporeal immunoadsorption using protein A-silica columns (PROSORBA columns). Of the 36 HIV-positive ITP patients treated, 29 received more than one treatment and were evaluated for response. Sixteen patients showed more than a 50% increase in their platelet counts. Platelet-associated IgG (PAIgG) and/or platelet-directed IgG and CIC were elevated in all patients. After four to eight treatments, 16 of 29 patients showed a 170% to 430% increase in platelet counts. A decrease in CIC and PAIgG was noted in responding patients. The median duration of response to date was 8 to 12 months. This treatment was associated with immune modulation and the development of an anti-F (ab')2 antibody response. The antibody functions by complexing with both platelet-binding IgG and CIC, neutralizing their binding capacity for platelets and enhancing their clearance from the circulation. Nine patients with mitomycin-C-induced hemolytic uremic syndrome (HUS) were also treated with PROSORBA columns. Pretreatment platelet counts were markedly reduced while a definite increase in platelet counts was observed upon completion of therapy. There was a decrease of hemolysis and stabilization of renal function in three patients. PROSORBA column treatment has demonstrated marked activity against both HIV-ITP and HUS, and has successfully freed patients from the bleeding diathesis associated with these syndromes.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Protein A immunotherapy in the treatment of cancer: an update.

Protein A, a naturally occurring Staphylococcus aureus cell surface protein, has the unusual property of binding circulating immune complexes and immunoglobulin G with high avidity. CIC have played a major role in cancer-associated immunosuppression. Thus, removal of the immunosuppressive agents, ie, the CIC, may lead to a modulation of the immunosuppression and a liberation of the immune system to perform an antitumor effect. In animal studies, protein A has been used in extracorporeal immunoadsorption columns and treatments have resulted in tumor shrinkage and antiviral responses. Our group developed a multicenter clinical trial to assess toxicity and antitumor responses with this biologic response modifier alone. This is an update of our original trial. We have now treated 142 patients for a total of 1,306 treatments. The patients consisted of 74 males and 68 females. Their age ranged from 7 to 83 years, with a mean of 50 years. The Karnofsky performance index values ranged from 40 to 95, with a mean of 80. Patients who received seven or more treatments were considered eligible for tumor response assessment, and all patients with one or more treatments were eligible for toxicity assessment. Thus, there were 101 patients eligible for tumor response and 142 eligible for toxicity response. The total response rate was 22 patients or 21.8% (partial remission [PR], 12 patients, 12%; less than PR, 10 patients, 10%). Response rates were similar in the 13 treatment centers. Toxicity was assessed in 142 patients. One thousand three hundred six treatments were assessed for treatment toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical Trials as Topic↗
PubMed1988

Protein A immunoadsorption in the treatment of malignant disease.

Circulating immune complexes (CIC) are known to be present in cancer patients and are responsible for much of the cancer-associated immunosuppression. Removal or modulation of these "blocking factors" can reverse the immunosuppression. Protein A from Staphylococcus aureus has the unusual property of binding to CIC with high avidity. Use of protein A as an immunoadsorbent in extracorporeal immunotherapy affinity columns has resulted in antitumor and antiviral responses in animals. Our group developed a multicenter trial to assess toxicity and antitumor response with this biologic response modifier alone. Overall, 24% (21 of 87 patients) had objective tumor regressions including both partial responses (PR) and less than PR. No complete responses (CR) were observed. Responses were observed in acquired immune deficiency syndrome (AIDS)-related Kaposi's sarcoma (six of 17 PR; two of 17 less than PR; overall, 47%), breast adenocarcinoma (five of 22 PR; three of 22 less than PR; overall response, 36%), colon adenocarcinoma, (one PR, one less than PR; overall response, 11%), and non-oat cell lung carcinoma (two of seven less than PR). The procedure was well tolerated and could be performed on an outpatient basis. No adverse reaction was observed in 735 of 1,113 treatments (66%). The most common adverse effect was an "influenza-like" syndrome consisting of fever and chills. Pain was present in 12% of the patients. There were no study-related deaths. Serum IgG and CIC levels did not statistically change due to therapy in responding or nonresponding patients. Complement levels remained within the normal range. Liver and renal tests remained stable throughout the study. In summary, protein A immunoadsorption of plasma is well tolerated in the outpatient clinic, has demonstrated antitumor activity in resistant solid tumors, and functions as a biologic response modifier.

Adolescent↗
PubMed1986

Acute renal failure due to bilateral ureteral obstruction by metastases from breast cancer.

Two female patients with metastatic breast carcinoma had acute renal failure secondary to metastatic ureteral obstruction. Retrograde pyelography showed bilateral segmental constriction and dilatation of the ureters with hydronephrosis. Drainage procedures reversed the renal failure in both patients. A review of the literature indicates that ureteral involvement is frequent in patients with malignancies.

Acute Kidney Injury↗
PubMed1981

Isolation of a stearoyl CoA Desaturase form Tetrahymena thermophila.

Cell free preparations of Tetrahymena thermophila contain an enzyme that catalyzes the direct desaturation of stearoyl CoA to octadecenoic acid. The enzyme is associated with the microsomal fraction of the ciliate. Substrate of the enzyme consists of either free stearic acid or stearoyl CoA. Both ATP and CoA are required when free stearate is the substrate and are also highly stimulatory when stearoyl CoA is the substrate. With stearoyl CoA as the substrate, either NADH or NADPH are required for desaturase activity. In presence of ATP and CoA, either NAD or NADP can replace NADH and NADPH. Desaturase activity is optimal when the enzyme is incubated at pH of 7.2 and a temperature of 30-35 degrees C. Highest levels of the stearoyl CoA desaturase are found in stationary phase ciliates grown at 35 degrees C.

Acyl Coenzyme A↗
PubMed1980

Osteosarcoma complicating familial Paget's disease.

A most unusual family with aggressive Paget's disease is reported. Three brothers out of 10 siblings developed the disease at a relatively early age. Two of these brothers developed an osteosarcoma and died. It is emphasized that very little information is available concerning the predisposition to severe polyostotic disease and even sarcomatous change when Paget's disease begins at a young age or is familial. Possibly the risk of these serious complications is then greater than when the disease is sporadic and begins later in life.

Adult↗