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Biomedical subjects

C A Johnson

Publications and source records attributed to C A Johnson.

At least 145 records · Page 8Linked to original sources
PubMed1997

Functional decline in the elderly: evidence for direct and stress-buffering protective effects of social interactions and physical activity.

Advances in medical technology and improvements in health behavior have greatly increased the proportion of Americans who survive into old age. Consequently, identifying environmental and behavioral factors that enhance or protect the health and functional capacity of older adults is an important goal. This study investigated the extent to which social interactions and physical activity can protect older adults from the declines in functional ability that typically occur with age and the extent to which they buffer the negative effects of widowhood on physical functioning. Data were from the Longitudinal Study of Aging, a six-year follow-up of over 7,000 respondents in the 1984 National Health Interview Survey. Using individual growth curve models which examine the effects of predictor variables on change over time, this study investigated how physical activity, social interactions, and widowhood are related to the rate of change in functional health over a six-year period. Results suggested that physical activity and social interactions each exerted independent effects on functional decline. In addition, physical activity and social interactions buffered the effects of widowhood on functional decline, especially in men who died before the end of the study. Results suggest a need for health promotion programs to encourage both physical and social activities in the elderly.

Activities of Daily Living↗
PubMed1997

Trazodone and triazolam: acute subject-rated and performance-impairing effects in healthy volunteers.

The present study compared the acute subject-rated and performance-impairing effects of trazodone and triazolam in seven healthy humans. Trazodone (50, 100 and 200 mg), triazolam (0.125, 0.25, 0.50 mg) and placebo were administered orally in a double-blind, crossover design. Drug effects were measured approximately 30 min before drug administration and repeatedly afterwards for 6 h. Trazodone and triazolam produced dose-related increases in subject-ratings of drug effect and sedation. The absolute magnitude of trazodone's and triazolam's effects was comparable across these measures, which suggests the doses tested were equivalent on some behavioral dimension. By contrast, triazolam, but not trazodone, increased subject ratings of "dizzy", "excited", "nervous", "restless", "stomach turning" and "itchy skin". Triazolam, but not trazodone, significantly impaired learning, recall and performance. The present findings suggest trazodone may be a viable alternative to benzodiazepine hypnotics like triazolam, especially when needing to minimize drug-induced impairment. Future research could extend the present findings by replicating them in a clinically relevant population such as individuals with histories of drug abuse.

Adult↗
PubMed1997

A multicenter comparison study of the Humphrey Field Analyzer I and the Humphrey Field Analyzer II.

PURPOSE: The purpose of the study is to determine the comparability of the 30-2 full-threshold program in the original Humphrey Field Analyzer (HFA) I to the same test procedure in the new Humphrey Field Analyzer II. METHODS: At each of five clinical centers, one eye of patients with ocular hypertension and normal visual fields, patients with early glaucomatous visual field loss, and patients with more advanced visual field loss were tested with the two instruments plus a retest on a separate HFA I. All participants had undergone at least one prior visual field examination. To minimize the influence of any residual learning or fatigue effects, the order of testing for the three visual field examinations was counterbalanced across subjects. A total of 250 patients were tested (81 patients with ocular hypertension, 81 patients with early glaucomatous visual field loss, and 88 patients with more advanced glaucomatous visual field loss). RESULTS: No statistically significant differences were observed between thresholds, visual field indices, or reliability indices obtained with the HFA I and the HFA II. The small differences between the two instruments were equivalent to the variation observed for test-retest measures using only the HFA I. These results were consistent across the range of visual field characteristics shown by the ocular hypertensive, early glaucoma, and moderate glaucoma patient groups. CONCLUSIONS: The authors' results indicate that there are no differences in the visual field results obtained with the HFA I and the HFA II. These findings suggest that with careful attention to test protocols, the HFA I and HFA II may be used interchangeably to observe patients, even within the context of multicenter clinical trials.

False Negative Reactions↗
PubMed1997

The popliteal bursa (Baker's cyst): an arthroscopic perspective and the epidemiology.

The purpose of this study was to establish the incidence of the anatomic structure, the popliteal bursa, in patients undergoing arthroscopy and to determine the relationship to associated clinical and pathological factors. Diagnostic arthroscopy was used to identify the presence of the popliteal bursa in 187 consecutive patients (195 knees). Thirty-seven percent of knees had a popliteal bursa identified by the communication with the posterior medial compartment. The cause of the popliteal bursa was not established by this study. This study refuted the causes proposed by others. The existing erroneous conclusions concerning the cause of the popliteal bursa were probably attributable to the failure to recognize the common continuity of the bursa and the knee joint. When the popliteal bursa is present (37%), it becomes symptomatic by responding to the intraarticular disease because of its continuity with the knee joint.

Adult↗
PubMed1997

An improved and combined reverse transcription-polymerase chain reaction assay for reliable detection of metastatic melanoma cells in peripheral blood.

The application of reverse transcription-polymerase chain reaction (RT-PCR) for detection of metastatic melanoma cells in peripheral blood has been used by a number of different scientific groups with both encouraging and discouraging results. We describe an improved, combined RT-PCR assay for tyrosinase mRNA, which can detect a single, viable melanoma cell in 10-15 ml of peripheral blood. The assay has been found to be highly sensitive, reproducible, cost-effective and clinically applicable. Furthermore, we developed a simple but effective procedure which prevents carry-over contamination. We present evidence indicating that the chance of obtaining normal melanocyte contamination with the needle prick during blood sampling is only 2% among all skin categories. It was found that the phenomenon of illegitimate transcription does not contribute to sporadic false positives. We conclude that the assay, as described here, is of clinical relevance and is a potentially powerful tool for studying various aspects of melanoma biology.

DNA Primers↗
PubMed1997

Phase I trial of tirapazamine in combination with cisplatin in a single dose every 3 weeks in patients with solid tumors.

PURPOSE AND METHODS: Tirapazamine (SR4233, WIN 59075) is a benzotriazine-di-N-oxide bioreductive agent that is selectively activated to a reactive DNA-damaging species in hypoxic tumors. Preclinical studies show that synergistic antitumor activity results from a schedule-dependent interaction between tirapazamine and several cytotoxic drug classes, including cisplatin. In a phase I combination study, tirapazamine (130 to 260 mg/m2) was administered as a 1-hour intravenous (IV) infusion beginning 3 hours before cisplatin (75 to 100 mg/m2). Thirteen patients received 41 courses of therapy. These patients had an excellent performance status and were not heavily pretreated. The predominant diagnosis was lung cancer. RESULTS: The major acute side effects were nausea and vomiting, which were controlled with an intensive antiemetic regimen. Other acute effects included diarrhea and muscle cramping, while with repeated dosing, anorexia and fatigue predominated. Full doses of each agent were well tolerated in combination, although in this previously treated population, fatigue increased markedly after three cycles of therapy. Partial responses were observed in two patients (one with non-small-cell lung cancer and one with breast cancer), and a minor response occurred in a patient with mesothelioma. Tirapazamine pharmacokinetics were linear with respect to increasing dose with a mean maximum plasma concentration (Cmax) of 5.97 +/- 2.25 microg/mL and an area under the concentration-time curve (AUC) of 811.4 +/- 311.9 microg/mL.min at 260 mg/m2. These results are consistent with other ongoing single-agent and combination studies and indicate that therapeutically relevant levels of tirapazamine are achievable in patients based on animal models. The mean cisplatin AUC was 285.6 +/- 46.4 microg/mL.min with mean Cmax values of 3.38 +/- 0.43 microg/mL at 75 mg/m2. The clearance of cisplatin was unaffected by coadministration with tirapazamine. CONCLUSION: This trial shows that in previously treated patients, full doses of cisplatin are well tolerated with increasing doses of tirapazamine up to 260 mg/m2. The observation of clinical responses in this trial supports the phase II investigation of this regimen.

Adult↗
PubMed1997

Immediate impact of thirty-two drug use prevention activities among students at continuation high schools.

Those teenagers who are unable to remain in the regular school system for reasons including substance use are transferred to a continuation high school. Generic comprehensive social-influence-drug-use-prevention-activities are less likely to be effective for use with these at risk youth. Thus, both classroom and self-instruction (main mode of instruction at continuation high schools) versions of 16 activities derived from different theoretical sources were tested and ranked on immediate outcome variables. 388 students from six continuation high schools were provided with a pretest-activity-posttest "component study" protocol. The scores on perceived quality ratings were standardized and averaged to permit easy comparisons across lessons. While yielding similar knowledge changes, students who received the health educator led activity consistently reported higher scores on perceived quality. Social influence-oriented lessons, in general, were rated of relatively low perceived quality. The present approach assisted in selection of the lessons with the greatest overall immediate impact.

Adolescent↗
PubMed1997

Screening for glaucomatous visual field loss with frequency-doubling perimetry.

PURPOSE: To conduct a preliminary evaluation of the efficacy of the frequency-doubling contrast test as a means of screening for glaucomatous visual field loss. METHODS: Contrast thresholds for frequency-doubled stimuli were obtained under four test conditions: superior hemifield, inferior hemifield, and central (5 degrees radius) targets using a method of adjustment (MOA); superior hemifield, inferior hemifield, and central targets using a modified binary search (MOBS); four quadrant stimuli and the central target using MOBS; and 16 stimuli (four per quadrant) and the central target using MOBS. One eye each of 36 patients with early (12), moderate (12), and advanced (12) glaucomatous visual field loss was tested, as was one eye each of 36 age-matched normal control subjects. RESULTS: For hemifield stimuli, the MOBS test procedure had better test-retest reliability, lower individual variation, and greater separation of the normal population and the population with glaucoma than did the MOA procedure. The use of progressively smaller, more localized stimuli produced successively better separation of glaucomatous and age-matched normal control eyes. Area under the Receiver Operating Characteristic curve was 0.81 for hemifield stimuli (sensitivity and specificity, 70% to 75%), 0.91 for quadrant stimuli (sensitivity and specificity, 83% to 85%), and 0.965 for the 16 stimuli (sensitivity 93%, specificity 100%). Test time was approximately 1.3 minutes for hemifields, 1.5 minutes for quadrants, and 5 minutes for the 16 targets. CONCLUSIONS: Preliminary results indicate that the frequency-doubled contrast test provides a quick, efficient means of screening for glaucomatous visual field loss. Test time is relatively short, test-retest reliability is good, and sensitivity and specificity for detection of glaucomatous visual field loss is very good. The use of the MOBS staircase procedure and small, localized stimuli result in the best performance for screening purposes. An expanded normative database and the use of more rapid suprathreshold screening strategies should enhance further the efficacy of this test.

Adult↗
PubMed1997

Arthroscopic debridement of knee joint arthritis: effect of advancing articular degeneration.

To determine the relationship between intraoperative findings and outcome of arthroscopic debridement for degenerative joint disease of the knee, data from 56 arthroscopies were analyzed. At an average follow-up of 49 months (range, 24 months to 63 months), results were good in 38 (68%) and poor in 18 (32%). No statistically significant relationship could be shown between the outcome and the presence of loose bodies, meniscal tears, or fat pad abnormalities. The presence of severe (grade IV) chondromalacia was associated with subsequent surgery, and when the medial compartment was involved, the likelihood of a poor outcome increased significantly. The likelihood of a successful outcome of arthroscopic treatment of degenerative joint disease of the knee is significantly and directly related to the condition of the articular cartilage.

Adult↗
PubMed1997

Which method of flicker perimetry is most effective for detection of glaucomatous visual field loss?

PURPOSE: The authors compared the efficacy of two different forms of flicker perimetry: temporal modulation perimetry (TMP), which measures contrast thresholds for a fixed temporal frequency, and critical flicker frequency (CFF), which measures the highest frequency for which flicker is detected at a fixed contrast. METHODS: The authors compared 16 patients with early to moderate glaucomatous visual field loss with 16 age-matched normal controls. Flicker stimuli consisted of 2 degrees diameter targets of 2 seconds in duration, presented in 44 locations throughout the central 30 degrees visual field. Flicker was presented within a cosine envelope to avoid temporal transients. For TMP, contrast sensitivity thresholds were measured for 8-Hz sinusoidal flicker; CFF thresholds were measured for a stimulus of 100% contrast. RESULTS: The results indicate that TMP and CFF produced similar test-retest reliability in normals. CFF had slightly better reliability in glaucoma patients. Receiver operating characteristic analysis revealed that TMP could provide better separation of normals and glaucoma patients than did CFF. Similar findings were obtained when the thresholds for both procedures were converted to Z scores. CONCLUSIONS: Both methods of flicker perimetry testing provide acceptable test-retest reliability, and both can distinguish normal subjects from glaucoma patients. However, TMP is more effective in separating normal subjects from glaucoma patients than CFF, suggesting that TMP is the method of choice for detecting glaucomatous damage using flicker perimetry.

Aged↗
PubMed1996

Transgenic mice expressing the thymus leukemia antigen fail to control cutaneous herpes simplex virus infection.

TL-transgenic mice expressing the thymus leukemia antigen demonstrate a lack of viral clearance following cutaneous HSV infection of the footpad. In this study, both uninfected and HSV-infected TL-transgenic mice demonstrate increased concentrations of IL-4 as well as decreased concentrations of IFN-gamma which may possibly underlie the impairment of viral clearance. Furthermore, lymphocytes from HSV-infected nontransgenic mice, adoptively transferred into HSV-infected TL-transgenic mice, promoted viral clearance and led to an increase in IFN-gamma production. Transgenic mice which were subcutaneously injected with IFN-gamma in the right footpad were also capable of clearing the viral challenge; however, clearance was restricted solely to the right footpad. These studies support the possibility of perturbations in the immune system of TL-transgenic mice and effectively demonstrate the utility of this model system in the study of HSV clearance, persistence, and potential spontaneous reactivation. Moreover, the TL-transgenic animals may provide a useful model system for additional studies requiring a host system skewed toward a Th2 phenotype.

Adoptive Transfer↗
PubMed1996

Anorexia nervosa: an overview.

Anorexia nervosa is a psychologic illness characterized by marked weight loss, an intense fear of gaining weight even though the patient is underweight, a distorted body image and amenorrhea. Anorexia primarily affects adolescent girls and occurs in approximately 0.2 to 1.3 percent of the general population. Complications of anorexia nervosa are numerous, involving almost every organ system, although most complications may be reversed when a healthy nutritional state is restored. Treatment may be administered on an inpatient or outpatient basis and involves nutritional and psychologic rehabilitation.

Anorexia Nervosa↗
PubMed1996

Lipophilic antifolates as agents against opportunistic infections. 1. Agents superior to trimetrexate and piritrexim against Toxoplasma gondii and Pneumocystis carinii in in vitro evaluations.

2,4-Diaminopteridines (21 compounds) and 2,4-diamino-5-methyl-5-deazapteridines (34 compounds) along with three 2,4-diamino-5-unsubstituted-5-deazapteridines and four 2,4-diaminoquinazolines, each with an aryl groups attached to the 6-position of the heterocyclic moiety through a two-atom bridge (either CH2NH, CH2N(CH3),CH2S, or CH2CH2), were synthesized and evaluated as inhibitors of the growth of Toxoplasma gondii in culture and as inhibitors of dihydrofolate reductase enzymes from T. gondii, Pneumocystis carinii, and rat liver. Exceptionally high levels of combined potency and selectivity as growth inhibitors of T. gondii and as inhibitors of the microbial enzymes relative to the mammalian enzyme were found among the 5-methyl-5-deazapteridines but not for the other heterocyclic types. Thirty of the 34 5-methyl-5-deaza compounds gave growth inhibition IC50 values lower than that of pyrimethamine (0.4 microM) with 14 compounds below 0.1 microM, values that compare favorably with those for piritrexim and trimetrexate (both near 0.02 microM). As inhibitors of T gondii DHFR, all but three of the 34 5-methyl-5-deaza compounds gave IC50 values in the order of magnitude with those of piritrexim (0.017 microM) and trimetrexate (0.010 microM), and 17 compounds of this group gave IC50 values versus P. carinii DHFR similarly comparable with those of piritrexim (0.031 microM) and trimetrexate (0.042 microM). Thirteen of these congeners gave both T. gondii growth inhibition and DHFR inhibition IC50 values of 0.10 microM or less, thus indicating facile penetration of the cell membrane. Eleven of these inhibitors of both T. gondii growth and DHFR have selectivity ratios (IC50 rat liver divided by IC50 T. gondii) of 5 or greater for the parasite DHFR. The highest selectivity ratio of nearly 100 belongs to the 5-methyl-5-deaza compound whose 6-substituent is CH2CH2C6H3(OCH3)2-2,5. This compound is over 10(3)-fold more selective for T. gondii DHFR than bridge homologue piritrexim (selectivity ratio 0.088), a compound now in clinical trials. The candidate with CH2NHC6H3(CH3)2-2,5 in the 6-position gave the highest P. carinii DHFR selectivity ratio of 4.0, which is about 60-fold more selective than trimetrexate (0.071) and 80-fold more selective than piritrexim (0.048) toward this enzyme. The 10 best compounds with respect to potency and selectivity includes six compounds bearing 2,5-disubstituted phenyl groups in the side chain (with little, if any, difference in effects of methyl, methoxy, or ethoxy), two side chains bearing 1-naphthyl groups, and two with 5,6,7,8-tetrahydro-1-naphthyl groups. Bridge groups represented in the 10 choice compounds are CH2NH, CH2N(CH3), CH2CH2, and CH2S. The high levels of both potency and selectivity among these agents suggest that in vivo studies now underway may lead to agents that could replace trimetrexate and piritrexim in treatment of toxoplasmosis and P. carinii pneumonia.

Animals↗
PubMed1996

Hereditary spherocytosis with spectrin deficiency due to an unstable truncated beta spectrin.

Red cell membrane protein analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and direct quantitation by radioimmunoassay or cytofluorometry defines four distinct subsets of patients with hereditary spherocytosis: Patients with isolated spectrin deficiency, combined spectrin and ankyrin deficiency, band 3 deficiency, and protein 4.2 deficiency. In regard to the first group, only one mutation of beta spectrin has been reported in the literature. We describe a spectrin variant characterized by a truncated beta chain, and associated with hereditary spherocytosis and isolated spectrin deficiency. The clinical phenotype consists of a moderate hemolytic anemia with spherocytosis and frequent spiculation of the red cells. We present the biochemical characteristics of this mutant protein and show that it constitutes only 12% of the total spectrin on the membrane. We show that the truncation of the protein is the result of a single point mutation at position +1 (G-->A) of the donor consensus splice site of intron 17 leading to an aberrant beta spectrin transcriptional message lacking exons 16 and 17. To elucidate the basis for the decreased amount of the truncated protein on the membrane and the overall spectrin deficiency, we provide evidence that the mutated gene is transcribed but its mRNA is less abundant than its normal counterpart in reticulocytes; we also show that the mutant protein is synthesized in decreased amounts in the cytoplasm of erythroid progenitor cells, and appears to be susceptible to proteolytic degradation. This mutant spectrin underscores the importance of the regulatory role played by the beta spectrin molecule in the assembly of alphabeta spectrin heterodimers on the membrane.

Base Sequence↗
PubMed1996

Type II human complement C2 deficiency. Allele-specific amino acid substitutions (Ser189 --> Phe; Gly444 --> Arg) cause impaired C2 secretion.

Type II complement protein C2 deficiency is characterized by a selective block in C2 secretion. The Type II C2 null allele (C2Q0) is linked to two major histocompatibility haplotypes (MHC) that differ from the MHC of the more common Type I C2 deficiency. To determine the molecular basis of Type II deficiency the two Type II C2Q0 genes were isolated and transfected separately into L-cells. Subsequent molecular biology, biosynthetic, and immunofluorescence studies demonstrated that C2 secretion is impaired in Type II C2 deficiency because of different missense mutations at highly conserved residues in each of the C2Q0 alleles. One is in exon 5 (nucleotide C566 --> T; Ser189 --> Phe) of the C2Q0 gene linked to the MHC haplotype A11,B35,DRw1,BFS, C4A0B1. The other is in exon 11 (G1930 --> A; Gly444 --> Arg) of the C2Q0 gene linked to the MHC haplotype A2,B5, DRw4,BFS,C4A3B1. Each mutant C2 gene product is retained early in the secretory pathway. These mutants provide models for elucidating the C2 secretory pathway.

Alleles↗
PubMed1996

Thymus-leukemia antigen interacts with T cells and self-peptides.

The functional role of the class Ib thymus-leukemia (TL) Ag expressed within the thymic cortex and intestinal mucosa of the mouse remains unknown. In an approach to elucidate the potential functionality of TL, we developed transgenic mice that ectopically express the H-2T18d gene product on essentially all nucleated cells through the control of a heterologous H-2Kb gene promoter. Transgenic mice demonstrated an increase in the number of CD4+ lymphocytes within the thymus and lymph nodes; these cells displayed an altered T cell receptor repertoire possibly suggesting a role for the ectopically expressed TL protein. The TL protein additionally displayed the characteristics of a bona fide transplantation Ag, because skin grafts from transgenic animals onto MHC- and minor histocompatibility Ag-matched nontransgenic recipient mice resulted in a rapid and vigorous immunologic rejection of the allograft. In MLR studies, transgenic stimulator cells induced the proliferation of responders to a level intermediate between genetically identical and H-2-disparate responder-stimulator combinations. The TL protein was also capable of stimulating cytotoxic T lymphocytes, thereby resulting in specific lysis of TL+ target cells. Further data demonstrated that the TL protein assembles with peptides that are modified at the amino terminus, and that TL retains these molecules at the cell surface. Together, these data suggest that H-2T18d is capable of interacting with T cells via a bound peptide. These data further support the possibility that TL may subserve a specialized function within the immunologic system.

Animals↗