PubMed Health⌕ Search

Biomedical subjects

S Zink

Publications and source records attributed to S Zink.

35 records · Page 2Linked to original sources
PubMed1995

Transport of L-arginine in arginine-deprived endothelial cells.

In vascular endothelium, L-arginine (ARG) plays a crucial role as a substrate for various metabolic pathways, one of which is the synthesis of bioregulatory nitric oxide. Transport of ARG across the cell membrane determines intracellular substrate availability. Membranous transport in turn may be dependent on the extra-to-intracellular gradient in ARG concentration. To test this hypothesis ARG transport was characterized in control and ARG-deprived endothelial cells (EC). Within a two-hour deprivation period a decrease of more than 50% in intracellular ARG concentration was observed. Initial uptake rates for ARG revealed no significant differences between ARG-deprived and control EC (30.0 +/- 2.7 vs. 30.6 +/- 2.1 pmol*(mg protein*min)-1). Two distinct ARG transporter components were observed dependent on extracellular ARG concentration. No significant differences between ARG-deprived and control EC were found with respect to the kinetics of these ARG transporter components. The present data suggest that in this model the transport rate of ARG into EC is not directly dependent on the intracellular ARG concentration. Thus, a feedback loop between intracellular ARG concentration and ARG transporters as a critical determinant for endothelial ARG-dependent pathways such as NO-synthesis appears highly unlikely.

Animals↗
PubMed1995

Fast-neutron therapy in advanced head and neck cancer: a collaborative international randomized trial.

PURPOSE: To compare the efficacy of fast-neutron radiotherapy with that of conventionally fractionated photon therapy in the management of patients with locally advanced squamous cell carcinoma of the head and neck. METHODS AND MATERIALS: Patients with Stage III or IV disease were randomized to receive either 20.4 Gy/12 fractions/4 weeks of neutrons or 70 Gy/35 fractions/7 weeks of photons (control). Between April 1986 and March 1991, 178 patients were entered, 169 of whom were eligible for analysis. The treatment arms were balanced for age, stage, and performance status, but not for primary site of origin. RESULTS: Complete response occurred in 70 and 52% with neutrons and photons, respectively (p = 0.006). Local regional failure at 3 years for all patients was 63% for neutrons and 68% for photons. Actuarial overall survival curves were virtually identical in both study arms, falling to 27% at 3 years. Acute toxicity was similar in the two arms, but late grade 3-5 toxicity was 40% with neutrons compared to 18% with photons (p = 0.008). CONCLUSION: Although the initial response rate was higher with neutrons, permanent local control and survival were not improved, and the incidence of late normal tissue toxicity was increased. As a result, fast-neutron therapy for advanced squamous cell carcinoma of the head and neck can only be recommended for patients in whom the logistic benefit of treatment in 12 sessions over 4 weeks outweighs the increased risk of late toxicity.

Adult↗
PubMed1995

Investigation of applicability of alanine and radiochromic detectors to dosimetry of proton clinical beams.

Cancer therapy studies using proton accelerators are underway in several major medical centers in the U.S., Russia, Japan and elsewhere. To facilitate dosimetry intercomparisons between these laboratories, alanine-based detectors produced at the National Institute of Standards and Technology and commercially available radiochromic films were studied for their possible use as passive transfer dosimeters for clinical proton beams. Evaluation of characteristics of these instruments, including the LET dependence of their response of proton energy, was carried out at the Institute of Theoretical and Experimental Physics. Results of absolute dose measurements were regarded as a preliminary step of dose intercomparison between ITEP and NIST. Measurements made in a number of experiments showed average agreement between the ITEP and NIST dosimetry standards to 2.5%.

Alanine↗
PubMed1995

Micro- and macrovascular endothelial cells in beta-adrenergic regulation of transendothelial permeability.

Barrier function of endothelial cells (EC) was modulated using beta-adrenergic agonists, e.g., isoproterenol (ISO) and formoterol (FOR). To get a direct comparison between EC from different vascular sources, we isolated EC from aorta (BAEC) and retina (BREC) of the same calf. For permeability studies, EC were cultured on polycarbonate filters. At confluency, transendothelial exchange of the diffusion marker fluorescein isothiocyanate-dextran was determined. Microvascular retinal EC monolayers are half as permeable as monolayers from macrovascular BAEC. When EC are stimulated with beta-adrenergic receptor (AR) agonists, monolayer permeability decreases, and the amount of intracellular adenosine 3',5'-cyclic monophosphate (cAMP) increases in both cell types. Comparison of the half-maximum concentrations causing change in permeability (pEC50) shows direct coupling between beta-AR and adenylate cyclase. The beta 2-selective agonist FOR stimulates cAMP synthesis in BAEC with a pEC50 value of 9.37 and decreases permeability with a pEC50 value of 9.72. In BREC, the pEC50 values of ISO concerning stimulation of cAMP synthesis and the decrease of permeability are also very similar, 5.32 and 5.34, respectively. BREC are not as sensitive to beta 2-AR agonists as BAEC. The pEC50 value of FOR influence on BREC permeability is 8.77 in comparison with 9.72 for BAEC. These results could be interpreted with different affinities of the beta 2-selective AR agonist in BREC and BAEC.

Adenylyl Cyclases↗
PubMed1995

Conformational analysis of the beta-amyloid peptide fragment, beta(12-28).

NMR and CD spectroscopy have been used to examine the conformation of the peptide, beta(12-28), (VHHQKLVFFAEDVGSNK) in aqueous and 60% TFE / 40% H2O solution at pH 2.4. In 60% TFE solution, the peptide is helical as confirmed by the CD spectrum and by the pattern of the NOE cross peaks detected in the NOESY spectrum of the peptide. In aqueous solution, the peptide adopts a more extended and flexible conformation. Broadening of resonances at low temperature, temperature-dependent changes in the chemical shifts of several of the CH alpha resonances and the observation of a number of NOE contacts between the hydrophobic side-chain protons of the peptide are indicative of aggregation in aqueous solution. The behavior of beta(12-28) in 60% TFE and in aqueous solution are consistent with the overall conformation and aggregation behavior reported for the larger peptide fragment, beta(1-28) and the parent beta-amyloid peptide.

Amino Acid Sequence↗
PubMed1994

Photon versus fast neutron external beam radiotherapy in the treatment of locally advanced prostate cancer: results of a randomized prospective trial.

PURPOSE: To evaluate the effectiveness of fast neutron radiation therapy in treatment of locally advanced carcinomas of the prostate. METHODS AND MATERIALS: From April 1986 to October 1990, 178 patients were entered on a prospective, multi-institutional randomized study of the NCI-sponsored Neutron Therapy Collaborative Working Group. This trial compared external beam photon irradiation (7000-7020 cGy) with external beam neutron irradiation (2040 ncGy) for patients with high-grade T2 or T3-4, N0-1, M0 adenocarcinomas of the prostate. Eighty-nine patients were randomized to each treatment. Six patients were subsequently judged to be ineligible, leaving 85 photon and 87 neutron randomized patients eligible for analysis. RESULTS: With a follow-up time ranging from 40 to 86 months (68 months median follow-up) the 5-year actuarial clinical local-regional failure rate for patients treated with neutrons was 11%, vs. 32% for photons (p < 0.01). Incorporating the results of routine posttreatment prostate biopsies, the resulting "histological" local-regional tumor failure rates were 13% for neutrons vs. 32% for photons (p = 0.01). To date, actuarial survival and cause-specific survival rates are statistically indistinguishable for the two patient cohorts, with 32% of the neutron-treated patient deaths and 41% of the photon-treated patient deaths caused by prostate cancer (p = n.s.). Prostate specific antigen (PSA) values were elevated in 17% of neutron-treated patients and 45% of photon-treated patients at 5 years (p < 0.001). Severe late complications of treatment were higher for the neutron-treated patients (11% vs. 3%), and were inversely correlated with the degree of neutron beam shaping available at the participating institutions. Neutron treatment delivery utilizing a fully rotational gantry and multileaf collimator did not result in an increase in severe late effects when compared to photon treatment. CONCLUSION: High energy fast neutron radiotherapy is safe and effective when adequate beam delivery systems and collimation are available, and it is significantly superior to external beam photon radiotherapy in the local-regional treatment of large prostate tumors.

Adenocarcinoma↗
PubMed1994

Moscow hospital-based proton therapy facility design.

An innovative design for a hospital-based proton therapy facility is described here in two versions: a single level (3600 m2) and a three-level plan (700-720 m2). The facility is designed to have 5 to 6 treatment rooms working simultaneously and independently of each other. The accelerator is a 250 MeV H-synchrotron, which produces a small external beam capable of pencil-beam scanning treatments. The small emittance of the beam yields cost savings in the size and weight of the magnets and the amount of concrete shielding. The beam delivery systems, including an isocentric gantry, are designed to use elements that are well known and thoroughly tested. Initial cost of a facility using this new design is estimated to be only 25-30% higher than construction of a facility delivering conventional photon treatments.

Cancer Care Facilities↗
PubMed1993

Neutron vs. photon radiation therapy for inoperable regional non-small cell lung cancer: results of a multicenter randomized trial.

PURPOSE: To determine, with a prospective, multicenter randomized study, whether fast neutron radiation therapy improves the outcome for patients with non-small cell lung cancer, as compared to conventional photon radiotherapy. METHODS AND MATERIALS: From September 1986 to March 1991, a total of 200 patients with inoperable regional non-small cell lung cancer were randomized to 20.4 Gy in 12 fractions with neutrons versus 66 Gy in 33 fractions with photons. Inoperable patients with Radiation Therapy Oncology Group Stages I, II, III, or IV(M0) disease, Karnofsky Performance Score > or = 70, and who had received no previous therapy for their non-small cell lung cancer were eligible for the study. Of the 200 patients randomized, a total of 193 patients, 99 on the neutron arm and 94 on the photon arm, were eligible for analysis. The two treatment groups were balanced with regards to prognostic factors. At the time of this analysis, the median at-risk follow-up was 33 months, with a minimum follow-up of 16 months. RESULTS: No difference in overall survival was observed; however, there was a statistically significant improvement in survival for patients with squamous cell histology (p = 0.02), and a trend toward improved survival for those with favorable prognostic factors (i.e., patients who were not T4, N3, and had no pleural effusion or weight loss > 5% from baseline) (p = 0.15), favoring the neutron-treated group. With the exception of skin and subcutaneous changes, acute and late toxicity was similar in both arms. CONCLUSION: In selected patients with inoperable regional non-small cell lung cancer (e.g., squamous cell histology, favorable prognostic factors), fast neutron irradiation provides a therapeutic benefit over conventional photon radiotherapy.

Adult↗
PubMed1993

Regulation of endothelial permeability by beta-adrenoceptor agonists: contribution of beta 1- and beta 2-adrenoceptors.

The barrier function of cultured, macrovascular endothelial cells derived from bovine aorta was analyzed using confluent monolayers of cells and measuring the exchange of fluorescein dextrans of different molecular masses. The effects of beta-adrenoceptor agonists with different selectivity for beta 1- and beta 2-adrenoceptors (AR) were investigated. Formoterol, a novel high-affinity agonist for beta 2-AR recently introduced in the treatment of bronchial asthma, showed a significant reduction of cell permeability with subnanomolar concentrations, whereas the catecholamines (-)-isoproterenol and (-)-norepinephrine only showed significant effects with micromolar concentrations. In order to elucidate if this difference in potential to regulate cell permeability is related to appropriate changes in the selectivity and affinity of the agonists for beta 2 AR, we investigated the beta AR-coupled adenylate cyclase (AC) in membranes from endothelial cells and compared AC stimulation with the binding of agonists to the receptors using [125I](-)-iodopindolol as radioligand. beta-Adrenoceptors revealed to be closely coupled to AC as assessed by a similar magnitude of effects by receptor agonists in comparison to GTP analogues and direct stimulants of AC activity. AC activity was increased by formoterol in parallel to its receptor occupancy of beta 2AR with nanomolar concentrations which were 50-fold higher than those used for the regulation of cell permeability indicating the existence of spare receptors. In contrast to formoterol, the catecholamines (-)-isoproterenol and (-)-norepinephrine stimulated AC activity through both beta 1AR and beta 2AR. From the overproportional high contribution of beta 1AR to AC stimulation (42%) in comparison to its low fraction (13%) in receptor binding we calculated that beta 1AR is 3-4-fold more effectively coupled to AC than beta 2 AR.

Adenylyl Cyclases↗
PubMed1993

Medical imaging databases. A National Institutes of Health workshop.

Development and implementation of a medical imaging database in a PACS-type environment that integrates all the patient data will impact directly on the quality of patient care. In addition, access to the wealth of information that is simply not accessible through the current technology, will contribute to improved disease detection and improved patient treatment, as well as produce significant new medical knowledge. Research and implementations must proceed in interdisciplinary environments which successfully combine the expertise and knowledge from the medical community with that of the database and computer science disciplines.

Database Management Systems↗
PubMed1989

Fast neutron therapy clinical trials in the United States.

The National Cancer Institute (NCI) began supporting clinical fast neutron clinical studies in the United States beginning in the early 1970s using physics-based cyclotrons and linear accelerators at a number of locations and facilities. The early work pointed out the handicaps imposed by the limitations of horizontal beams and low energy neutrons. This, combined with some encouraging, clinical results using neutrons and photons in a mixed mode of therapy, prompted the NCI in 1979 to initiate a 10-year contract program to design, develop, and build hospital-based neutron therapy machines and to conduct phase III clinical trials. As we approach the end of the 10-year effort, three hospital-based neutron facilities are currently operational-at the University of Washington, Seattle; University of California at Los Angeles: and M. D. Anderson Hospital at University of Texas System Cancer Center, Houston. Phase III trials are in progress in four sites: head and neck, prostate, and lung tumors, and cancers of radioresistant histologies, such as melanoma, renal cell carcinoma, and sarcomas of the soft tissue and bone. The contractors will continue to receive limited NCI support to complete the clinical studies.

Clinical Trials as Topic↗
PubMed1982

Pion radiotherapy at LAMPF.

Clinical investigations of pi meson radiotherapy were conducted by the Cancer Research and Treatment Center of the University of New Mexico and the Los Alamos National Laboratory from 1974 until 1982. Two hundred and thirty patients have been treated for a variety of locally advanced primary and metastatic neoplasms. One hundred and ninety-six patients have been followed for a minimum of 18 months. Crude survival data range from 11% for unresectable pancreatic carcinoma to 82% for Stages C and D1 adenocarcinoma of the prostate. Acute tolerance of normal tissues is approximately 4500 pion rad in 36 fractions over 7 weeks. Severe chronic reactions have appeared with increasing frequency after doses in excess of 4000 pion rad.

Adenocarcinoma↗
PubMedDate not supplied

The promise of a new technology: knowledge-based systems in radiation oncology and diagnostic radiology.

The revolutionary changes in computer capabilities in the last decade, both in software and hardware, have opened new doorways for the uses of computers in radiation oncology and diagnostic radiology. Knowledge-based systems offer the potential to function as aids, consultants and advisors in the differential diagnosis of disease, staging, selection of therapy and treatment management and delivery for cancer patients. These computer-based systems can also provide for the training and teaching of radiotherapy and diagnostic radiology residents, and act as advisors and teachers to the medical physicists, dosimetrists and technicians. Following a brief history of the development of knowledge-based systems, the general capabilities of computer-based physician workstations in a department of radiation oncology are described.

Expert Systems↗