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Biomedical subjects

C R Johnson

Publications and source records attributed to C R Johnson.

At least 19 recordsLinked to original sources
PubMed1992

Oxygen binding constants and stepwise enthalpies for human and bovine hemoglobin at pH 7.6.

A high-precision thin-layer gas-solution microcalorimeter has been developed to study the binding reactions of gaseous ligands with ligand-binding macromolecules in a manner analogous to that of the Gill thin-layer optical apparatus [Doleman & Gill (1976) Anal. Biochem. 87, 127]. We have generated differential heat-binding curves of oxygen binding to human and bovine hemoglobin in phosphate buffer at pH 7.6, with the enzyme-reducing system of Hayashi et al. [(1973) Biochim. Biophys. Acta 310, 309]. Experiments were conducted at a number of different temperatures in order to expand the data field, allowing for separation of enthalpy and free energy parameters. This type of experimental analysis makes no assumptions of optical linearity between the various heme groups and reveals that the triply ligated species is measurably significant for both human and bovine hemoglobin. It was also determined that the concentration of doubly ligated species of bovine hemoglobin is relatively low. The experiments indicate that the reactions for both hemoglobins are enthalpy-driven for oxygen stepwise additions 1, 2, and 4 while being entropy-driven for step 3. Human hemoglobin oxygen-binding experiments were also performed with the Gill thin-layer optical apparatus under solution conditions identical to those used in the calorimeter. The experiments revealed that if optical linearity is assumed, the overall third equilibrium constant is negative or near zero. This indicated that either the optical cell's performance is much poorer than the thin-layer calorimeter or there is an appreciable nonlinear optical effect.

Animals↗
PubMed1992

Concomitant boost technique using accelerated superfractionated radiation therapy for advanced squamous cell carcinoma of the head and neck.

Of 142 patients irradiated for American Joint Committee on Cancer Stage III or IV head and neck carcinoma, 100 patients were eligible for analysis with a minimum follow-up of 12 months. In one group, 50 patients were treated with conventional once-a-day (QD) fractionation to doses in excess of 6600 cGy. The other 50 patients were treated prospectively with accelerated superfractionated radiation therapy using a concomitant boost twice-a-day schedule (BID). Patients received conventional fractionation (180 cGy/fraction) combined with a boost field of 160 cGy/fraction BID after a 4-hour to 6-hour interval 3 days per week during part of their treatment course. After 3 years, locoregional tumor control was 62% in the BID group versus 33% in the QD group (P = 0.003). Disease-free survival was 60% and 30%, respectively, for the BID and QD groups (P = 0.002), and adjusted survival was 66% and 38%, respectively, for the BID and QD groups (P = 0.03). Overall survival approached statistical significance in favor of the BID group (P = 0.06). Complete tumor responses were observed in 63% of patients treated in the BID group 1 to 3 months after completion of radiation therapy. Of these, 84% remain free of local recurrence. Of the 19 patients with persistent disease 1 to 3 months after treatment, 47% remain locally controlled. Superfractionated accelerated radiation therapy produced superior local control and disease-free and adjusted survival rates relative to a group of patients treated QD.

Carcinoma, Squamous Cell↗
PubMed1992

A computer model for the study of electrical current flow in the human thorax.

Electrocardiography has played an important role in the detection and characterization of heart function, both in normal and abnormal states. In this paper we present an inhomogeneous, anisotropic computer model of the human thorax for use in electrocardiography with emphasis on the calculation of transthoracic potential and current distributions. Knowledge of the current pathways in the thorax has many applications in electrocardiography and has direct utility in studies pertaining to cardiac defibrillation, forward and inverse problems, impedance tomography, and electrode placement in electrocardiography.

Computer Simulation↗
PubMed1992

Incompletely resected advanced squamous cell carcinoma of the head and neck: the effectiveness of adjuvant vs. salvage radiotherapy.

Between 1982 and 1988, 441 patients were treated at the Medical College of Virginia for AJC Stage III and IV squamous cell carcinoma of the head and neck. We report here on 84 patients whose tumors were incompletely resected based on histopathological margins of 1 mm or less. Of these 84 patients, 49 were treated with surgery alone and 35 received immediate postoperative irradiation to doses of 50-70 Gy. The two patient groups are comparable with respect to stage of disease, age, male/female and racial ratios. This retrospective analysis, based on follow-up of 24-110 months, gives actuarial locoregional tumor control and survival data. The local control and disease-free survival rates in the combined modality group are significantly superior at the p = 0.0006 and p = 0.0003 levels, respectively, relative to the group treated with surgery alone. Patients in the combined modality group also experienced a significantly improved adjusted and overall survival, p = 0.005 and p = 0.01, respectively. The administration of postoperative irradiation was not associated with an increased rate of complications. The benefit of radiotherapy on survival was only seen when given as postoperative treatment but was lost in patients treated for salvage after tumor recurrence.

Adult↗
PubMed1992

Thin-layer microcalorimetric studies of oxygen and carbon monoxide binding to hemoglobin and myoglobin.

A thin-layer gas-solution microcalorimeter has been developed to study the binding reactions of gaseous ligands with ligand binding macromolecules. We have measured the enthalpy of binding oxygen and carbon monoxide to horse myoglobin, human hemoglobin A0 and sperm whale myoglobin in phosphate buffer at pH 7.6, with the enzyme reducing system of Hayashi. Reactions of human hemoglobin were also done under various buffer conditions in order to elucidate the Bohr effect. These binding reactions were found not to exhibit a detectable enthalpy change over the temperature range of 10 degrees C to 25 degrees C. The enzyme reducing system was shown to react with oxygen in a manner that releases a substantial amount of heat. This problem was corrected by using a minimum amount and by placing the buffer and enzyme system in the reference cell effectively cancelling the oxygen enzyme reaction heat as well as the heat of gas dissolution. It was also demonstrated that glucose-6-phosphate, one of the reducing system components, in 50 mM concentrations can influence the heat of binding oxygen and carbon monoxide to hemoglobin. This effect was shown to be absent in the myoglobins and also with hemoglobin at glucose-6-phosphate concentrations less than 5 mM.

Animals↗
PubMed1992

Postoperative radiotherapy in head and neck carcinoma with extracapsular lymph node extension and/or positive resection margins: a comparative study.

In head and neck carcinoma, the finding of extracapsular lymph node extension and/or positive resection margins portends poor locoregional control and survival. The effectiveness of postoperative radiotherapy in these patients has been controversial due to insufficient studies comparing resected patients with those also receiving radiation. Between 1982 and 1988, 441 radical head and neck resections were performed at the Medical College of Virginia. Pathologic review of these cases identified 125 with extracapsular lymph node extension and/or positive resection margins. Of these, 43 had extracapsular lymph node extension only, 24 had both positive resection margins and extracapsular lymph node extension, and 58 demonstrated positive resection margins only. Surgery alone was performed in 71 of these patients while 54 cases received surgery and postoperative radiotherapy, (combined modality treatment) CMT. Radiotherapy doses ranged from 50 to 70 Gy. The surgery alone and combined modality treatment groups were comparable with respect to the distribution of positive resection margins and extracapsular lymph node extension. Slightly more CMT patients had clinical T4 disease compared with the surgery alone group (22% vs 14%). Slightly fewer combined modality treatment patients had clinical N0 necks than the surgery alone group (20% vs 29%). Multivariate analysis was performed with the variables T, N stages, radiotherapy, margin status, primary tumor sites, microscopic and macroscopic extracapsular lymph node extension, number of positive lymph nodes, number of nodes with extracapsular lymph node extension. Locoregional control was maintained at 5 years in 59% of the combined modality treatment group and 31% of the surgery alone group (p.0001). Subgroup analysis likewise reveals significant differences favoring the combined modality treatment group for positive resection margins only (49% vs 41%; p = .04), extracapsular lymph node extension only (66% vs 31%; p = .03) and extracapsular lymph node extension+positive resection margins (68% vs 0%; p = .001). Adjusted survival also shows a significant benefit of combined modality treatment vs surgery alone for the entire group (72% vs 41%; p = .001). Multivariate analysis revealed that the use of radiotherapy is a strongly favorable variable for local control and adjusted survival. Macroscopic extracapsular lymph node penetration and positive resection margins are unfavorable independent variables for local control. T-stage is the only variable predicting local control in the combined modality group. Extracapsular extension remains an important negative prognostic variable for survival in both treatment groups. In conclusion, this study demonstrates a locoregional control and survival benefit for postoperative radiotherapy in patients with the high risk pathologic findings of extracapsular lymph node extension and positive resection margins.

Carcinoma, Squamous Cell↗
PubMed1991

Accelerated superfractionated irradiation for advanced carcinoma of the head and neck: concomitant boost technique.

Between 1980 and 1988, 94 patients with AJCC Stage III and IV squamous cell carcinoma of all sites of the upper aero-digestive tract were treated with radiotherapy. We report here on 62 patients who are followed for a minimum of 2 years. Of these, 30 patients were treated with conventional once-a-day radiotherapy and 32 patients were irradiated using an accelerated superfractionation regimen during part of the treatment course. The altered fractionation schedule employed a concomitant boost technique with clinically demonstrable disease being irradiated twice-a-day during the first or second half of the treatment course. Daily radiation fractions were 1.8 Gy and the boost field was treated with 1.6 Gy after a 4- to 6-hr interval. No significant differences in acute treatment toxicity were observed in the two treatment groups. Patients treated with conventional and accelerated fractionation regimens experienced 36 months actuarial local tumor control rates of 40% and 67% (p = 0.03), respectively, which translated into an actuarial disease-free survival of 40% and 64% (p = 0.04). The increased locoregional control rates in patients treated with accelerated fractionation were associated with an adjusted and overall survival advantage at the p = 0.05 level. We conclude that our regimen of accelerated superfractionated irradiation with shortening of the treatment course resulted in improved control and survival rates at conventional doses of 68.4 to 73.8 Gy.

Adult↗
PubMed1989

Binding of oxygen and carbon monoxide to the hemocyanin from the spiny lobster.

A high precision, two-dimensional study of oxygen and carbon monoxide binding to Panulirus interruptus hemocyanin has been carried out. Global data analysis of three types of experiments, probing the molecule in its various states of CO and O2 ligation, revealed the entire hexamer to be the basic allosteric unit involved in a two-state mechanism. The co-operativity and linkage of the two ligands are presented in terms of derivative Hill plot surfaces extended along co-ordinates of CO and O2 activities giving a detailed and comprehensive view of the binding behavior. Among the findings is an apparent high co-operativity of carbon monoxide binding at high oxygen activity. The results are discussed in view of a general mechanism for co-operative behavior found in larger hemocyanin aggregates concerning "nested" allosteric interactions.

Animals↗
PubMed1988

Pharmacodynamic evaluation of ofloxacin and trimethoprim-sulfamethoxazole in vaginal fluid of women treated for acute cystitis.

Vaginal colonization with Escherichia coli is an integral step in the development of acute cystitis, and persistent vaginal coliform colonization may also be a predisposing step to recurrent urinary tract infections. For this reason, we evaluated antibiotic concentrations in the vaginal fluid, serum, and urine and the vaginal colonization by E. coli of 56 women receiving either ofloxacin (200 mg orally twice a day) or trimethoprim-sulfamethoxazole (TMP-SMX) (160/800 mg orally twice a day) for the treatment of acute cystitis. Ofloxacin and trimethoprim both penetrated into vaginal fluid to a considerably greater extent than sulfamethoxazole. Among 33 patients given ofloxacin, the concentration of the drug in vaginal fluid during one dosage interval ranged from 1.6 to 21.6 micrograms/ml. In 21 women given TMP-SMX the range of drug concentrations in vaginal fluid was 2.6 to 32.5 micrograms/ml for TMP and 1.0 to 6.2 micrograms/ml for SMX. Treatment with both ofloxacin and TMP-SMX remarkably reduced vaginal colonization by E. coli during and up to 30 days after therapy. For the ofloxacin-treated women, eradication of vaginal E. coli was associated with a high ratio of drug concentration in vaginal fluid to that in serum. We conclude that ofloxacin and TMP both achieve high concentrations in vaginal fluid and are equally successful in eradicating E. coli from the vagina.

Administration, Oral↗
PubMed1988

Aquatic therapy for an ALS patient.

The opportunity to participate in wellness programming can be particularly valuable to persons who must be prepared to deal with continuing gradual physical deterioration for the rest of their lives. During time periods when his health was stable, without evidence of a rapid progression of the illness, Charlie was able to devote some energy to the pursuit of swimming, an activity he had enjoyed for many years. The WETSwim program provided the opportunity for Charlie to take an active role in the management of his physical and psychological status. In an environment where he was able to overcome barriers to participation, Charlie could explore aquatic recreation activities and resume a leisure role. He experienced the opportunity to learn and practice swimming skills, develop an area of performance to a mastery level, and improve his quality of life. Occupational therapists are no longer confined to the traditional locations for and methods of providing treatment. Encouraged by the changing economics of health care, they seek alternative ways of providing quality health care (Frazian, 1985). Persons with short-term physical dysfunction, as modern consumers, are taking greater initiative in the medical management of their dysfunction and seek alternatives to passive forms of treatment. Persons with chronic or long-term physical disabilities, in addition to having basic needs for optimal sensory-motor function and ADL independence, are becoming increasingly interested in physical fitness. The WETSwim program offers a wide range of opportunities, medical and recreational, functional and social, to the consumer with physical dysfunctions.

Amyotrophic Lateral Sclerosis↗
PubMed1987

Sulfoxides.

Explore the source record for details and available documents.

Indicators and Reagents↗
PubMed1986

Discoid lupus erythematosus and X-linked chronic granulomatous disease.

X-linked chronic granulomatous disease (CGD), a defect of leukocyte bactericidal capacity, was seen in three generations of a large kindred. The association of discoid lupus erythematosus (DLE) with CGD was noted. Recurrent antigenic stimulation leading to autoantibody formation may explain the apparently increased frequency of DLE in female carriers of CGD. A screen for CGD, the nitroblue tetrazolium test, is suggested for females with DLE who have experienced suppurative infections or who have a family history of early childhood deaths or recurrent infections.

Adult↗
PubMed1978

Electron spin resonance studies of the solution structure of vanadyl amino acid complexes and mixed ligand complexes of oxalate.

Esr and electronic spectra of complexes of the general composition VO(AA)2 and VO(ox)(AA) have been characterized; AA = gly, his, cys, pro, val, met, asp amino acids. Spectra of the formulation VO(ox)(LL) (with LL = imidazole plus monodentate oxalate, histamine plus monodentate oxalate, histidine, cysteine, 4-imidazolepropionic acid, mercaptopropionic acid, ethylenediamine and ethanolamine) have been used to deduce a self-consistent assignment of AL, a ligand donor additivity constant contribution to the observed hyperfine splitting, Aiso. Values of AL are sensitive to inductive effects in the ligand structure. The solution structures and likely coordination geometries of VO(his)2, and VO(cys)22-- are discussed. The role of the imidazole moiety as a sigma donor and sulfhydryl sulfur as a pi acceptor is observed in VO(AA)2 and VO(ox)(AA) complexes.

Amino Acids↗