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PubMedDate not supplied

Mitomycin-C as a prototype bioreductive alkylating agent: in vitro studies of metabolism and cytotoxicity.

The bioreductive alkylating agents are prodrugs for chemotherapy which are enzymatically reduced within cells to species capable of alkylating biological molecules and producing cytotoxic damage. Studies presented in this report show that MIT-C has the characteristics expected of a bioreductive alkylating agent: activation to alkylating species occurs more readily under hypoxic conditions and the drug is selectively cytotoxic to hypoxic cells.

Alkylating Agents↗
PubMed1992

A prototype radiation oncology clinical information processing system on a personal computer (network).

Software has been developed that facilitates prospective computer entry of the clinical contents of a radiation oncology chart in a way that assists in retrospective analyses. This software, which has been operational since 1988, now contains detailed clinical information on over 500 patients treated since that time, and limited information on over 3000 children treated since 1970. The system has been programmed using the FoxPro database management system, and may be run on an IBM compatible or Macintosh personal computer either alone or in a networked environment. Information is transcribed as routine patient dictations that require no extra personnel for entry. Standard printouts are the conventional notes compatible with the existing paper chart. Exportation of patient records is facilitated by means of built-in facsimile. The software has been designed to generate detailed reports automatically, including the statuses of selected patients or groups, lists of those who are behind in follow-up, and reports of specific events (e.g., mucositis) that occur before, during, or after therapy using free-text searches. Complete reconstruction of the patient's clinical radiation oncology chart is also included. Other abilities include calculation of Kaplan-Meier survival, relapse-free survival, and local control rates, statistical comparison between survival curves, and radiation dose-response. Exportation of data to statistical and graphics packages is also possible. For pediatric patients, a program to predict stature loss has been incorporated. Use of this system can enhance one's ability not only to follow patients but also to monitor and report their outcome continually. With the need to report institutional experiences and increasing demands to monitor quality assurance, such a system can be of great benefit.

Electronic Data Processing↗
PubMed1992

Construction and use of two alpha-human atrial natriuretic peptide-fragment affinity chromatography columns in the isolation of C- and N-terminal epitope-specific antibodies for use in a prototype alpha-hANP biosensor.

Two alpha-human atrial natriuretic peptide (alpha-hANP) based affinity chromatography columns were produced by covalently immobilizing the C- and N-terminal epitopes of alpha-hANP. The stationary phase was made from a controlled-pore-glass bead solid support, which was silanized and treated with sulphosuccinimidyl 4-(maleimidomethyl)cyclohexyl carboxylate before the individual fragments were immobilized by substitution at their thiol groups. These columns were used to isolate alpha-hANP-specific antibodies from a goat anti-alpha-hANP serum, which were then further sorted according to their epitope specifity. These C- and N-terminal epitope-specific antibodies were in turn used as components in the construction of an alpha-hANP biosensor based on an enzyme-linked immunosorbent assay (ELISA) sandwich principle. Initial in vitro testing of the sensor using a physiological alpha-hANP solution showed a reproducible response to the peptide. There is to date no other equally fast, sensitive and precise method available to detect this peptide. This alpha-hANP sensor may prove to be an invaluable aid in human medicine as a monitor of patient status during transplant surgery, for example, an area inaccessible to radioimmunoassay and normal ELISA techniques.

Amino Acid Sequence↗
PubMed1991

Synthesis, purification and stability of no carrier added radioiodinated 1,1-bis(4-hydroxyphenyl)-2-iodo-2-phenylethylene (IBHPE), a prototype triphenylethylene estrogen-receptor binding radiopharmaceutical.

A triphenylethylene compound [1,1-bis(4-hydroxyphenyl)-2-iodo-2-phenylethylene; IBHPE] has been labeled by halodestannylation with 123I at a specific radioactivity of 13,200 Ci/mmol (by in vitro receptor assay) after HPLC purification. The corresponding 80mBr-labeled compound (BrBHPE), which has a 3-fold higher affinity for the estrogen receptor, was previously prepared and examined as a potential therapeutic radiopharmaceutical exploiting Auger electron toxicity. Stability of IBHPE was a concern because free iodide was generated when HPLC solvents were removed with a stream of nitrogen in a glass vial; however, decomposition was minimal when polypropylene vials were used, and ethanol solutions of [123I]IBHPE were stable for several days at 0-4 degrees C. Tissue distribution studies of IBHPE after intraperitoneal injection to mature female rats showed highest estradiol-inhibitable uptake in the peritoneal estrogen-receptor rich tissues (uterus, ovaries and vagina) at 30 min. Specific uptake (percent dose per gram) in the pituitary, and peritoneal target tissue-to-blood ratios were greater at 2 h than 30 min. In immature female rats, uterus-to-blood ratios of greater than 50, progressively lowered by increasing diethylstilbestrol levels, were obtained. These data demonstrate good binding of IBHPE to the estrogen receptor in vivo, in spite of extensive non specific binding in in vitro estrogen receptor assays. Most of the label in the uterus at 1 h after injection was still unchanged IBHPE. Our results suggest that IBHPE or related 123I-labeled iodovinyl triphenylethylenes could have diagnostic or therapeutic radiopharmaceutical utility.

Aging↗
PubMedDate not supplied

Effects of human recombinant alpha and gamma and of highly purified natural beta interferons on simian Spumavirinae prototype (simian foamy virus 1) multiplication in human cells.

The present study demonstrates the inhibitory effect of human recombinant interferons (r-Hu-IFN) alpha and gamma, and that of highly purified natural human interferon beta on the replication of simian foamy virus type 1 (SFV1) in human AV3-cell cultures. All IFN led to strong inhibition of the SFV1 cytopathic effect. Electron microscopy showed a 70 to 95% decrease in viral particles. Significant inhibition of virus-associated reverse transcriptase activity was found in supernatant fluids of infected IFN-treated cultures. Metabolic labelling of the virus confirmed the inhibition of extracellular release of SFV1. PAGE analysis of immunoprecipitates indicated a reduction in viral-specific protein bands. Altogether, these results indicate that the mechanism of inhibition of Spumavirinae infection by interferon differs from that described for the other Retroviridae, and particularly for types B, C and D viruses. Our data is of therapeutic interest since Spumavirinae have been linked to pathological processes such as de Quervain thyroiditis.

Cell Line↗
PubMed1990

Effects of two prototypic polychlorinated biphenyls (PCBs) on lipid composition of rat liver and serum.

Mature male Sprague-Dawley rats received a single IP injection of either 2,2',4,4',5,5'-hexachlorobiphenyl (HCB), 3,3',4,4'-tetrachlorobiphenyl (TCB) (300 microm/kg) in corn oil (10 ml/kg) or the corn oil vehicle alone, and were killed four days later after having been fasted overnight. The vehicle control group consisted of rats which were allowed free access to feed as well as pair-fed animals. Lipid analyses were conducted on liver, hepatic microsomes and serum. TCB- (but no HCB-) treatment resulted in a statistically significant increase in total liver lipids and triglycerides. Liver phospholipids remained unchanged. Both PCBs increased the cholesterol and phospholipids content of the liver microsomal fraction. Serum lipids measured were not statistically different from control values. While HCB had little effect on the fatty acid composition of liver lipids, TCB caused an increase in C 18:1 (n-9) and a decrease in C 20:4 (n-6). Both PCBs increased C 18:0 in the hepatic microsomal fraction, but TCB also decreased C 16:0. Neither PCB altered the fatty acid composition of serum total lipids. These data are consistent with the concept that specific alterations in lipid metabolism are dependent on the structure of the PCB.

Journal Article↗
PubMed1991

The HIV-1 Rev protein: prototype of a novel class of eukaryotic post-transcriptional regulators.

Complex retroviruses, including Human Immunodeficiency Virus Type 1 (HIV-1), are characterized by the ordered temporal expression of the various viral gene products in infected cells. This effect is mediated by a novel class of RNA-sequence-specific regulatory proteins typified by the Rev trans-activator of HIV-1. Evidence suggests that Rev regulates HIV-1 gene expression by intervening in the normal pathway of eukaryotic mRNA processing and transport.

Base Sequence↗
PubMed2004

Experiences with a workstation prototype for softcopy reading within the Bavarian mammography recertification program: workstations and education.

RATIONALE AND OBJECTIVES: In January 2002, the Bavarian Statutory Health Care Administration ("Kassenärztliche Vereinigung Bayerns", KVB) started a recertification program for quality assurance and quality improvement in mammography reading. MATERIALS AND METHODS: All accredited radiologists and gynecologists are asked to prove their qualification every 1-2 years. The recertification program requires the physicians to read 50 cases randomly selected from a larger collection of high-quality test cases. The portion of malignant and benign cases corresponds to the requirements of the German National Association of Statutory Health Insurance Physicians ("Kassenäztliche Bundesvereinig ung", KBV). In order to perform the recertification in a manageable manner a decentralized approach (test at different locations in parallel) was preferred over a centralized one. Therefore, the X-ray films were digitized and converted to DICOM Digital Mammography format to be read on a softcopy device. To verify the applicability of digitized mammograms for recertification purposes, a comparative study with 32 trained radiologists and gynecologists was performed. RESULTS: A system of two high-resolution/high-contrast monitors (2048 X 2560 pixels, > or = 350 cd/m2) in combination with a 5 mega-pixel dual-head graphics adapter with calibrated output was chosen for the mammography workstation. The software was implemented according to the particular requirements of this program. As a result, the comparative study showed that there was no significant difference in the error rate of the reported findings between conventional film and softcopy reading. CONCLUSION: The first intermediate results of this quality initiative are promising. As of 2003, the test is mandatory for all mammography-reading physicians in Bavaria.

Breast Neoplasms↗
PubMed2005

Clinical potentials of the prototype 256-detector row CT-scanner.

RATIONALE AND OBJECTIVES: To evaluate clinical potentials of the 256-detector row computed tomography (CT) in healthy volunteers. MATERIALS AND METHODS: Eight healthy males (22-63 years) participated in the present study. They underwent a noncontrast-enhanced examination with a contiguous axial scan mode either for head, chest, abdomen, or pelvis. Dose was the same as routinely used for multislice CT examinations. Image quality was interpreted by three board-certified radiologists. RESULTS: With the 256-detector row CT, 0.5-0.8 mm isotropic volumetric data could be acquired in one rotation. Main promising findings are as follows. Three-dimensional structures were visualized clearly in the multiple planes without secondary reconstruction, whereas the axial images had nearly the same image quality as conventional CT. Shading or streak artifacts were observed at the edge of the scan region. The latter are also known as Feldkamp artifacts. Coronal chest images showed a motion artifact from the heart beating. CONCLUSION: The 256-detector row CT promises to be useful in clinical applications with its ability to provide three-dimensional visualization of fine structures. The Feldkamp artifacts observed did not generally affect interpretation of images. Investigations are now continuing on image correction along the craniocaudal direction to improve the overall image quality.

Adult↗
PubMed2004

An emergency department response to severe acute respiratory syndrome: a prototype response to bioterrorism.

STUDY OBJECTIVE: On March 13, 2003, Singapore physicians were alerted about an outbreak of atypical pneumonia that became known as severe acute respiratory syndrome (SARS). I describe the application of an emergency department (ED) disaster response plan to manage the SARS outbreak. METHODS: The ED implemented protection for staff, patients, and facility; infection control measures; and disaster-response workflow changes. The Ministry of Health, Singapore, centralized SARS cases in the hospital, and the ED became the national screening center. A screening questionnaire and a set of admission criteria were applied after assessment of clinical features and chest radiograph findings. RESULTS: For the duration of the outbreak that ended on May 31, 2003, the ED screened 11,461 persons for SARS, of whom 1,386 (12.9%) were admitted to rule out SARS and 235 (17%) were confirmed to have SARS. Among 10,075 persons discharged from the ED, there were 28 reattending patients who were admitted and diagnosed with SARS, giving an undertriage rate of 0.3% (95% confidence interval [CI] 0.1% to 0.4%). The sensitivity of an ED admission for SARS was 89.4% (95% CI 85.6% to 93.1%), and specificity was 89.7% (95% CI 89.2% to 90.3%). The positive predictive value was 17% (95% CI 15.7% to 18.4%), and the negative predictive value was 99.7% (95% CI 99.6% to 99.8%). No patient contracted SARS as a result of an ED visit. After full implementation of protective measures, 1 ED nurse with undiagnosed diabetes mellitus was treated for suspected SARS. CONCLUSION: Although the SARS outbreak was not a bioterrorism event, the ED disaster response was applicable in the outbreak's management. The use of a screening questionnaire and admission criteria enabled the ED to screen, treat, and safely discharge the majority of the patients.

Adult↗
PubMed2004

Subacute cutaneous lupus erythematosus: 25-year evolution of a prototypic subset (subphenotype) of lupus erythematosus defined by characteristic cutaneous, pathological, immunological, and genetic findings.

Subacute cutaneous lupus erythematosus (SCLE) represents a widespread, photosensitive, nonscarring, nonindurated form of lupus erythematosus (LE)-specific skin disease. SCLE lesions are associated with a distinctive immunogenetic background including the production of Ro/SS-A autoantibodies. Individuals who have SCLE skin lesions as a component of their presenting illnesses represent a distinctive subset (subphenotype) of LE that enjoys a good prognosis with respect to life-threatening systemic manifestations of LE. SCLE skin lesions can be triggered by a number of different drugs the majority of which are capable of producing photosensitivity drug reactions in nonlupus patients. Single agent or combination aminoquinoline antimalarial therapy will suffice for 75% of SCLE patients. The remaining 25% will require other forms of systemic antiinflammatory therapy (e.g., diaminodipenylsulfone (Dapsone), thalidomide) or systemic immunosuppressive-immunomodulatory therapy. The etiopathogenesis of SCLE skin lesions is thought to result from four sequential stages: (1) inheritance of susceptibility genes (HLA 8.1 ancestral haplotype [C2, C4 deficiency, TNF-alpha-308A polymorphism], C1q deficiency); (2) loss of tolerance/induction of autoimmunity (ultraviolet light, photosensitizing drugs/chemicals, cigarette smoking, infection, psychological stress); (3) expansion/maturation of autoimmune responses (high levels of autoantibodies (Ro/SS-A), immune complexes, autoreactive T-cells); and (4) tissue injury/disease induction resulting from various autoimmune effector mechanisms (e.g., direct T cell-mediated cytotoxicity, antibody-dependent cell-mediated cytotoxicity).

Humans↗
PubMed2004

The NADPH oxidase of professional phagocytes--prototype of the NOX electron transport chain systems.

The NADPH oxidase is an electron transport chain in "professional" phagocytic cells that transfers electrons from NADPH in the cytoplasm, across the wall of the phagocytic vacuole, to form superoxide. The electron transporting flavocytochrome b is activated by the integrated function of four cytoplasmic proteins. The antimicrobial function of this system involves pumping K+ into the vacuole through BKCa channels, the effect of which is to elevate the vacuolar pH and activate neutral proteases. A number of homologous systems have been discovered in plants and lower animals as well as in man. Their function remains to be established.

Animals↗
PubMed2004

Coils and tubes releasing heparin. Studies on a new vascular graft prototype.

Coiled metallic guidewires find widespread use, for instance in interventional cardiology. It is known that release of heparin from the surface of guidewires is advantageous to prevent formation of thrombotic emboli. New coiled tubular structures, having larger inner and outer diameter as compared to guidewires, are presented. In theory these tubes can be used as interposition vascular grafts. Ten coiled tubes with an internal diameter of 690 microm were made. Five different adherent polymeric coatings with increasing hydrophilicity were used. Five tubes contained heparin in the coating and the other five were unheparinised controls. The five tubes containing heparin were studied with respect to heparin release in vitro (amount released, kinetics), and immobilised heparin that is exposed at the surface. All tubes were studied with a direct cell contact assay using 3T3 mouse fibroblast cells, a dynamic thrombin generation test, and endothelial cell growth onto the coils. It was found that the heparinised tubes lead to very little thrombin formation. It is argued that this is due to heparin that is immobilised and exposed at the inner surface of such tubes. Furthermore the coils showed to be cytocompatible and endothelial cells adhere and proliferate well onto the coils. This concept is believed to hold promise for further development of small vascular grafts.

3T3 Cells↗
PubMed2004

Comparison of a prototype magnetoresistive biosensor to standard fluorescent DNA detection.

We present a comparative analysis of a magnetoresistive biosensor to standard fluorescent DNA detection. The biosensor consists of giant magnetoresistive (GMR) type Cu/Ni(80)Fe(20) multilayers in the second antiferromagnetic coupling maximum. Each of the 206 elements of the magnetoresistive biosensor is patterned into a spiral-shaped line that can cover the area of a typical DNA spot (70 microm diameter). The probe DNA is assembled on top of the sensor elements in different concentrations ranging from 16 pg/microl to 10 ng/microl. Complementary biotin-labeled analyte DNA is hybridized to the probe DNA at a concentration of 10 ng/microl. A number of different commercially available magnetic microspheres are investigated to determine the most appropriate markers. The experimental comparison shows that the relative sensitivity of the magnetoresistive biosensor is superior to the fluorescent detection at low probe DNA concentrations.

Biosensing Techniques↗