PubMed Health⌕ Search

Biomedical subjects

R L Stephens

Publications and source records attributed to R L Stephens.

At least 127 records · Page 7Linked to original sources

Proton NMR investigation of Ln3+ complexes of thymopoietin 32-36.

The pentapeptide Arg-Lys-Asp-Val-Tyr (TP5) is a biologically active fragment of thymopoietin, the thymic hormone that induces selective T-cell differentiation. The formation of lanthanide(III) complexes of TP5 is demonstrated through the observation of Tb3+ fluorescence enhancement. The equilibria, stoichiometry and solution conformation of the La3+, Pr3+ and Yb3+ complexes of TP5 have been investigated using NMR spectroscopy. In addition, the dissociation constants of two methyl ester analogs of TP5 have been studied. Evidence is presented supporting an interaction between the arginine guanidino N epsilon H and the aspartate carboxylate of TP5. Binding of Ln3+ appears to be accompanied by a disruption (or weakening) of this interaction and a concomitant increase in the 180 degrees rotamer population for the aspartate carboxylate group. The observed trends in the magnitudes of the dissociation constants and the rotamer populations appear to suggest that, although a significant amount of monodentate complexes may also exist, the metal ion binds predominantly to both carboxylates in a bidentate fashion.

Amino Acids↗

Conformation of angiotensin II. Evidence for a specific hydrogen bonded conformation.

The peptide amide hydrogen exchange rate of human angiotensin II in H2O have been measured at room temperature by the transfer of solvent saturation method. The data are consistent with the assumption of a highly motile dynamic equilibrium between folded and highly solvated conformations. The NH of His6 is observed to exchange more slowly than predicted, suggesting that it is a participant in an internal hydrogen bond. Several models previously suggested in the literature for the conformation of the peptide in aqueous solution are examined, and most are found to be inconsistent with the exchange data. Evidence in support of a structure for the Ile5-His6 fragment of the hormone involving a C7eq-C5 bend is presented.

Angiotensin II↗

The conformation of angiotensin II. II. The rates of peptide NH exchange with solvent for [Asn1, Val5]angiotensin II, angiotensin III and saralasin.

The amide hydrogen exchange rates in H2O of two angiotensin agonists (angiotensinamide and angiotensin III) and one angiotensin antagonist (saralasin) have been measured at room temperature by the transfer of solvent saturation method. The NH of His6 is observed to exchange more slowly than predicted for all three peptides, suggesting that it is a participant in an intramolecular hydrogen bond. The NH-C alpha H 1H-NMR coupling constants are measured and found to be constant over the pH range of 5.0 to 6.5. The results are compared with those previously obtained for human angiotensin II and interpreted in terms of a dominant three-dimensional structure common to all four molecules. Two models for this structure are evaluated using the observed NH-C alpha H coupling constants and the reported activity of conformationally restrained derivatives.

Angiotensin Amide↗

Effective streptozocin therapy for metastatic pancreatic polypeptide apudoma.

An apparently complete remission of metastases in the liver from a resected pure pancreatic polypeptide apudoma occurred following intra-arterial and intravenous administration of streptozocin to a patient in a family with multiple endocrine adenopathy, type 1. Plasma concentrations of human pancreatic polypeptide constitute an excellent marker system for the detection and assessment of tumor status before and after surgical and streptozocin therapy.

Adult↗

Heat acclimatization, its decay and reinduction in young Caucasian females.

The loss of heat acclimatization and the number of days necessary for reinduction to the acclimatized state as a function of length of the decay period were studied for periods of four, eight, and twelve days. Six females between 18 and 30 years of age (mean VO2 max = 38.7 mL/kg/min) were concurrently heat acclimatized for ten days by treadmill walking at 5.0 km/hr for 100 minutes per day in an environment of 33.5 degree C WBGT. Both 35% and 75% relative humidities were utilized to achieve at 33.5 degree C WBGT with half the subjects exposed to each condition. Physiological measurements included heart rate, sweat rate, core temperature, and mean skin temperature. Of these measurements, only the sweat rate proved not to be affected by any of the independent variables. Predictive equations were developed for heart rate, core temperature and mean skin temperature for decay periods of four through twelve days in length and end of work values attainable for one through four days of successive work after decay. Significant relationships were found in all cases, with the correlation coefficients ranging from 0.73 to 0.86. Both levels of humidity created the same physiological responses from the subjects, suggesting that the ability of WBGT to evaluate heat stress is independent of the humidity level.

Acclimatization↗

Phase I evaluation of chlorozotocin: single dose every six weeks.

A phase I trial of chlorozotocin was completed for the single dose every six week schedule. At 250 mg/m2 i.v. push, excessive thrombocytopenia, nausea, and anorexia occurred. Two cases of cholestatic jaundice were seen, and one patient had worsening of his diabetes mellitus after one course. Partial response or prolonged disease stabilization with increased survival was documented in four of seven patients with non-small cell carcinoma of the lung. A starting dose of 225 mg/m2 is recommended for good risk patients with little or no prior bone marrow toxicity from chemotherapy or irradiation. A dose of 200 mg/m2 is recommended for patients with limited previous treatment and good bone marrow reserve.

Anorexia↗

Vinblastine (VLB), bleomycin (BLEO), cis-diamminedichloroplatinum (DDP) in disseminated extragonadal germ cell tumors. A Southwest Oncology Group Study.

Nineteen patients considered to have metastatic primary extragonadal germ cell cancer were entered on a Phase II chemotherapy study using as induction therapy a combination of vinblastine (VLB) 12 mg/m2 day 1, bleomycin (BLEO) 15 U/m2 I.V. or I.M. twice weekly, and cis-diamminedichloroplatinum (DDP) 15 mg/m2 days 1-5, with vinblastine and DDP repeated at 28-day intervals for four months. All complete or partial responders were then placed on a maintenance regimen of vinblastine 12 mg/m2 alternating monthly with actinomycin-D 1.5 mg/m2 day 29, and chlorambucil, 10 mg/m2 P.O. days 32-37. There were three complete remissions (CR's), six partial remissions (PR's), and two stable disease. The response rate (CR's mpr's) was 56%; however the mean duration of response was only two months (range, 1-8 months). Drug toxicity was significant and there was one toxic death. Unlike patients with disseminated testicular cancer, patients with primary metastatic extragonadal germ cell carcinoma appear to do less well on this particular drug regimen. Further investigation using different drug regimens seems necessary.

Adult↗

Superiority of adriamycin-containing combination chemotherapy in the treatment of diffuse lymphoma: a Southwest Oncology Group study.

As a part of an ongoing prospective controlled trial, the Southwest Oncology Group compared the results of treatment of advanced non-Hodgkin's lymphoma with two CHOP regimens (cyclophosphamide, adriamycin, vincristine and prednisone with either low-dose bleomycin or BCG by scarification) to a COP regimen (cyclophosphamide, vincristine and prednisone) with low-dose bleomycin (COP-Bleo). The study design emphasized histopathology review and systematic restaging to define complete remission (CR). Confirmed rates of CR for 443 evaluable patients were 59% for 286 patients receiving the CHOP regimens and 59% for 157 patients receiving COP-Bleo. Rates of CR were higher for patients with nodular lymphoma (69%) compared to those with diffuse lymphoma (54%) (p = 0.005). For patients with nodular lymphoma there was no difference in CR rates according to treatment. For patients with diffuse lymphomas the CR rate was higher with the CHOP programs (58%) than with COP-Bleo (44%) (p = 0.10). Overall duration of CR and survival was significantly longer for patients with nodular lymphoma compared to diffuse lymphoma (p less than 0.01). At this time, remission duration and survival were similar regardless of induction regimen used in patients with nodular lymphoma. However, in patients with diffuse lymphoma, the duration of CR and overall survival were improved by treatment with the CHOP regimens compared to COP-Bleo (p = 0.02). Thus, in this controlled study we have demonstrated that initial combination chemotherapy employing the CHOP regimen was a superior remission induction therapy for patients with diffuse lymphoma.

Antineoplastic Agents↗

Electron spin resonance studies on properties of ceruloplasmin and transferrin in blood from normal human subjects and cancer patients.

The methodology of blood sample preparation and analysis has been examined to further evaluate the technique of electron spin resonance (ESR) for possible use in detecting cancer and in monitoring the progress of cancer therapy. Frozen whole blood and serum samples from 278 normal donors and 97 cancer patients were studied by ESR for signal intensity from Cu+2 bound to ceruloplasmin (g factor = 2.05). The signal from this species (Cu+2-CP) in serum rose sharply during the first two hours of storage at room temperature after being drawn from the subject, and then reached a plateau. The average Cu+2-CP ESR signal intensity was significantly different for control groups of males, females not taking estrogen medication, and females taking estrogens. The mean ESR signal intensities of Cu+2-CP from cancer patients separated into the same groups as the control data were approximately twice as great as the mean control levels. Total serum copper levels were correlated with ESR intensities of Cu+2-CP and indicated that the ratio of Cu+2/Cu+1 in CP is higher in serum from cancer patients than from controls.

Age Factors↗

Incidence of hemorrhagic complications in patients with cancer.

The incidence and type of hemorrhage were studied in 718 patients with solid tumors. All patients were receiving myelosuppressive chemotherapeutic agents. Seventy-five patients (10.4%) experienced one or more episodes of hemorrhage. Bleeding was due to tumor invasion in 25 patients (33.3%), was due to disseminated intravascular coagulation in seven patients (9.3%), and was unrelated to malignant neoplasms or drug treatment in six patients (8%). Thirty-seven patients (49.3%) had hemorrhages associated with drug-induced thrombocytopenia. There was a quantitative relationship between the incidence of hemorrhage and the platelet count for both the thrombocytopenic group and the total group of patients with hemorrhages from all causes. The incidence of hemorrhage was low until the platelet count decreased below 10,000/cu mm.

Blood Cell Count↗

Rapid development of diffuse pulmonary infiltrates in histiocytic lymphoma.

A 24-year-old man with documented histiocytic lymphoma developed a nodular interstitial infiltrate, as shown by chest roentgenograms during a 10-day period of observation. He also developed fever, chills, and purulent sputum. Open-lung biopsy revealed histiocytic lymphoma without evidence of infection. This case demonstrates that lymphoma can cause rapid development of infiltrates observable by roentgenography. Because the infiltrate could be neoplastic or infectious, empiric therapy without an exact diagnosis is not warranted.

Adult↗