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Biomedical subjects

R Johnson

Publications and source records attributed to R Johnson.

At least 271 records · Page 15Linked to original sources
PubMed1993

F reticulocyte response in sickle cell anemia treated with recombinant human erythropoietin: a double-blind study.

Studies on baboons and preliminary observations in three patients with sickle cell anemia (SS) suggested that high doses of pulse administered recombinant human erythropoietin (rHuEPO) stimulate F-reticulocyte production. We now report on the administration of rHuEPO in a double-blind format to ascertain frequency of response and potential precipitation of side effects. Ten patients were enrolled, but one was discontinued due to the indication of a blood transfusion. Of the other nine, five received rHuEPO in escalating doses (from 400 to 1,500 U per kg twice daily [BID] per week), alternating with a placebo, in blinded fashion. The second group, consisting of four patients, followed an identical protocol (except starting dose was 1,000 U/Kg, BID per week) and were iron supplemented during treatment. The criterion of response was a transient doubling (as a minimum) of the steady-state F-reticulocyte level. We found that none of the five patients in the first group responded to rHuEPO, and two of them became iron deficient, as judged by a significant decrease in ferritin. Of the second group, four patients responded with F-reticulocyte increases. In three patients, open label administration of rHuEPO confirmed the effect. We observed seven painful episodes during this study, two during the EPO administration and five during the placebo arm. Three patients were phlebotomized because the hemoglobin level increased 1.5 g/dL more than steady-state levels. Of the six patients followed-up by percent dense cell determinations, one exhibited increased levels during periods of the treatment, whereas the other five showed no change. No anti-rHuEPO antibodies were detected. We conclude that rHuEPO can stimulate F-reticulocyte response in some patients with sickle cell anemia, without apparent negative clinical side effects. The state of iron stores may be critical. Whether higher doses of rHuEPO and/or a different regimen might induce sustained F cells and fetal hemoglobin increases remains to be determined.

Adolescent↗
PubMed1993

Growth pressure can drive early chick lens geometries.

Over a number of morphological stages during chick lens morphogenesis, a flat plate of cuboidal ectodermal cells infolds to form a deep cup of tall, pyramidal lenticular cells. This invagination process is accompanied by asynchronous cellular multiplication over a basal region constrained by an adhesive extracellular matrix. A lens placode is formed as the cells crowd into columnar "palisades." A lens cup forms as the cells pyramidalize owing to basal nuclear movements. Invagination ends when the opening into the lens cup is closed to form a lens vesicle. In this paper, equations are developed that provide a quantitative, mathematical formulation of an earlier theory that explains this invagination as a growth driven process. The equations take into account the lens cell cycle, the extracellular matrix, and nuclear migratory behaviors. Based on the equations, geometries simulating the morphological stages and the cell cycle phases are generated for the 1st day of lens development. The mathematical formulation of lens invagination helps demonstrate how growth pressure alone can be the primary driving force for tissue folding. In this view, recruitment occurs before the shape changes; and cell-autonomous mechanisms of invagination, involving the cytoskeleton or differential adhesion alone, offer inadequate explanations of these changes.

Animals↗
PubMed1993

Caffeine enhanced measurement of mutagenesis by low levels of gamma-irradiation in human lymphocytes.

The well-known action of caffeine in synergizing mutagenesis (including chromosome aberrations) of agents like ionizing radiation by inhibition of cellular repair processes has been incorporated into a rapid procedure for detection of mutagenicity with high sensitivity. Effects of 5-10 rads of gamma-irradiation, which approximate the human lifetime dose accumulation from background radiation, can be detected in a two-day procedure using an immortalized human WBC culture. Chromosomally visible lesions are scored on cells incubated for 2 h after irradiation in the presence and absence of 1.0 mg/ml of caffeine. An eightfold amplification of scorable lesions is achieved over the action of radiation alone. This approach provides a closer approximation to absolute mutagenicity unmitigated by repair processes, which can vary in different situations. It is proposed that mutagenesis testing of this kind, using caffeine or other repair-inhibitory agents, be employed to identify mutagens in their effective concentrations to which human populations may be exposed; to detect agents such as caffeine that may synergize mutagenic actions and pose epidemiologic threats; and to discover effective anti-mutagens. Information derived from the use of such procedures may help prevent cancer and newly acquired genetic disease.

Caffeine↗
PubMed1993

Determination of plasma and brain concentrations of SCH 39166 and their correlation to conditioned avoidance behavior in rats.

Plasma and brain concentrations of the dopamine D1 receptor antagonist, SCH 39166, were measured and compared to behavioral activity in the conditioned avoidance response paradigm (CAR). SCH 39166 was administered at two behaviorally active doses (1 mg/kg, SC and 10 mg/kg, PO) and the time course for CAR activity was compared with the plasma and brain concentrations of unconjugated SCH 39166. Conjugation and N-demethylation of SCH 39166 after oral administration were also determined and first pass metabolism examined. Results from these studies demonstrated a similar time-dependent disappearance of unconjugated SCH 39166 from both the plasma and brain, independent of route of administration. Brain concentrations of SCH 39166 were approximately 5-fold higher than corresponding plasma concentrations, regardless of route. However, plasma and brain concentrations of unconjugated SCH 39166 were higher after SC administration of 1.0 mg/kg, than after PO administration of 10 mg/kg, suggesting a substantial first pass metabolism of SCH 39166. In addition, total (conjugated and unconjugated) plasma concentrations of SCH 39166 were at least 10-fold higher than unconjugated concentrations of SCH 39166 after PO administration of 10 mg/kg, demonstrating that a high proportion of drug was conjugated. Metabolism to the N-desmethyl analog, SCH 40853, was observed after PO administration of 10 mg/kg SCH 39166 and a high proportion of conjugation of the desmethyl analog was also seen. Finally, plasma concentrations of unconjugated SCH 39166 exhibited a high positive correlation (r = 0.934, P < 0.001) with brain concentrations of unconjugated SCH 39166.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1993

Eosinophilic pleocytosis in coccidioidal meningitis: frequency and significance.

PURPOSE: Coccidioidal meningitis (CM) is a major source of morbidity and mortality in endemic regions. The diagnosis of CM is a clinical challenge. Eosinophilic pleocytosis (EP) is an uncommon finding and present in a relatively limited number of conditions. In order to determine the frequency and the prognostic significance of EP in CM, we conducted the present study. PATIENTS AND METHODS: Retrospective chart review of all patients diagnosed as having CM between 1986 and 1991 at Kern Medical Center. All patients had clinical and cerebrospinal fluid (CSF) findings confirmatory of CM. RESULTS: Nineteen patients (70%) in the study group had EP, and of these, 8 patients (30%) met the criteria for eosinophilic meningitis (greater than or equal to 10 eosinophils/mm3). No correlation was found between EP and age, sex, race, results of complement fixation test for coccidioidal antigen in CSF or serum, peripheral eosinophilia, or outcome. CONCLUSION: The presence of EP is a frequent observation in CM. Although we did not demonstrate any prognostic correlation with EP, this finding is of major diagnostic significance and its presence should bring attention to the diagnosis of CM.

Adult↗
PubMed1993

Marginal gap width of a new refractory porcelain system.

This study was conducted to determine whether matching the physical properties of refractory die material to porcelain could increase the marginal accuracy of porcelain inlays. Restorations made with a matched Fortune refractory porcelain system were compared with restorations made with unmatched Vita porcelain and Polyvest refractory material. Thirty addition-silicone impressions were made of a master mesioocclusodistal inlay preparation. Fifteen refractory dies were made for each of the refractory materials. The dies were prepared and the porcelain applied according to the manufacturer's specifications. Three measurements of marginal gap were recorded adjacent to premarked points on each proximal box by use of a Unitron microscope with micrometer adjustment. The mean marginal gap was 51.24 +/- 20.84 microns for the matched material and 100.43 +/- 17.30 microns for the unmatched material. A Student's t-test was performed, which showed a significantly greater mean gap for the unmatched system compared with the matched system (t[28] = 7.03, p < 0.005). The results indicate that a matched refractory porcelain system can produce restorations with significantly improved marginal accuracy.

Dental Alloys↗
PubMed1993

Transoral-transpharyngeal approach to the upper cervical vertebrae.

The classical operative approaches to the cervical spine include the posterior one and the anterior exposure along the sternomastoid muscle. However, neither of these are helpful in exposing the upper cervical vertebrae, especially the odontoid process, atlas, and axis. We have used the transoral-transpharyngeal exposure for lesions of the odontoid process and upper (first to third) cervical vertebrae in six patients. The pathologic processes included rheumatoid disease and fracture of the cervical vertebrae, suspected tumor with compression of the spinal cord, basilar invagination, and compression of the medulla. In all six patients, the exposure was excellent, and postoperative morbidity was minimal. Tracheostomy was performed routinely in all these patients. In five patients, vertebral stabilization was performed as a secondary procedure a few days after the initial anterior decompressive surgery. The transoral-transpharyngeal approach appears to be relatively easy. It is associated with minimal complications and provides excellent exposure of the odontoid and upper cervical vertebrae for a microneurosurgical approach. Modifications of this approach include incision of the soft palate, excision of a portion of the hard palate, and, occasionally, transmandibular median labio-mandibulo-glossotomy (Trotter's) approach. Although the technique was described initially approximately 35 years ago, this neglected anatomic approach will facilitate cooperative efforts between head and neck surgeons and neurosurgeons.

Adult↗
PubMed1993

Five to eight year results of the Johnson-Elloy (Accord) total knee arthroplasty.

Between February 1982 and December 1985, 133 knees in 107 patients were replaced with a cemented Johnson-Elloy (Accord) total knee arthroplasty. Thirty-five knees were lost during the follow-up period because of death in 29, revision in 3, infection in 1, and refusal of follow-up evaluation in 2. The results of the remaining 98 knees in 76 patients with a 5-8 year follow-up period are presented. The procedure was carried out in all cases presenting for surgery, irrespective of pathology and degree of deformity. The range of flexion achieved as a mean of 93.5 degrees in the osteoarthritic group and 100 degrees in the rheumatoid arthritic group. Eighty-seven percent of the osteoarthritic group and 95% of the rheumatoid arthritic group achieved between 10 degrees and 50 degrees of rotation at 90 degrees of flexion, which was maintained for the duration of the study. Adequate stability in both groups, valgus-varus and rotation in extension, and anteroposterior in flexion was achieved. Survivorship was 97.7% at 80 months.

Aged↗
PubMed1993

Is air medical scene response for illness appropriate?

The purpose of this study was to determine the appropriateness of air medical scene response for illness. The study consisted of a retrospective chart review of a two-helicopter urban air medical transport program with a transport volume of 1,700 flights annually. During the study period, January 1988 through March 1990, 68 patients were transported by helicopter from scene of illness to a tertiary care facility. In cases in which patients could be managed appropriately locally, air transport was deemed unnecessary. Of the 68 patients with illness, 40 were males and 28 were females; the average age was 39.2 years (from a range of 0 to 93). The average transport time was 46.3 minutes. Dispatch diagnoses were cardiac arrest (20), seizure (14), myocardial infarction (8), overdose (6), stroke (5), labor (4), respiratory distress (3) and miscellaneous (8). The discharge (final) diagnosis was different from dispatch diagnoses in 10 patients (14.7%). Fifty-four patients (79.4%) required no tertiary care, and 30 of them were discharged from the emergency department or were pronounced dead there or at the scene. The results of the study indicate air medical response to scene of illness did not appear justified in this study. Transport should be local, by ground, with subsequent tertiary care being arranged as needed. Further prospective study is warranted.

Aircraft↗
PubMed1993

Radioactive waste management at a large university and medical research complex.

A radioactive waste management program was developed for a large university and medical research complex to contain costs and to reduce the impact of the Low-Level Radioactive Waste Policy Act. The program takes advantage of decay-in-storage, incineration, special packaging techniques, and increased training and awareness. A series of metrics are presented to evaluate the effectiveness of the radioactive waste management program. Through the use of this program the amount of waste disposed of at commercial burial sites decreased from 98% to 1.61% of the waste generated. At the same time the volume of waste generated per laboratory declined by almost 45%, from 0.35 m3 (12.31 ft3) to 0.19 m3 (6.80 ft3).

Academic Medical Centers↗
PubMed1993

CAR2, a prestalk cAMP receptor required for normal tip formation and late development of Dictyostelium discoideum.

Extracellular cAMP serves as a primary signaling molecule to regulate the development of Dictyostelium discoideum. It is required for chemotaxis, aggregation, cytodifferentiation, and morphogenetic movement. The receptors for cAMP are members of the family of cell-surface receptors that are linked to G proteins and characterized by seven putative transmembrane domains. Previously, we have isolated the gene for the cAMP receptor subtype 1 (CAR1) from Dictyostelium and suggested that several genes related to CAR1 were present in the genome. Here, we describe a family of cAMP receptor genes of Dictyostelium and the isolation and function of the gene for the cAMP receptor subtype 2, CAR2. CAR2 is structurally similar to CAR1. Overall, their transmembrane and loop domains are approximately 75% identical in amino acid sequence; however, their carboxyl termini are quite dissimilar; CAR2 possesses homopolymeric runs of histidines and asparagines that are absent from the corresponding region in CAR1. Although CAR1 is maximally expressed during the early stages of development, CAR2 is expressed only after cells have aggregated and, then, preferentially in prestalk cells. Transgenic Dictyostelium that have had their wild-type CAR2 gene replaced by a defective copy using homologous recombination proceed through early development but are detained at the tight mound stage. CAR2 may be required for cAMP-directed sorting of prestalk cells during pattern formation within the aggregation mound. Furthermore, although prestalk genes are expressed normally in aggregates that lack CAR2, they exhibit an enhanced expression of prespore-specific mRNA. Previously, we had shown that there was a requirement for CAR1 during early development. The present results demonstrate that the multiple responses of Dictyostelium to cAMP are regulated by distinct cAMP receptors that are encoded by unique genes.

Amino Acid Sequence↗
PubMed1993

On the neural generators of the P300 component of the event-related potential.

The triarchic model of P300 amplitude (Johnson, 1986, 1988a) postulated that the overall amplitude of the P300 recorded at any given electrode site represented the summation of activity from different neural generators, each related to the processing of a different type of information. However, neither of these original accounts provided an explicit description of the methods required to establish experimentally the presence of multiple neural sources. This paper reviews the triarchic amplitude model, the subsequently obtained data that support the postulated presence of multiple generators underlying the P300, and the methods used to demonstrate the presence of these multiple sources. These methods are straightforward because it is only necessary to show that the portions of P300 amplitude associated with different experimental variables have different scalp distributions. The implications of the multiple-generator basis of P300 on such factors as component definition, neural source analyses, and the cognitive processes underlying its activity are discussed.

Arousal↗
PubMed1993

Cutaneous metastasis of neuroendocrine carcinoma of uterine origin.

We report a case of a 33-year-old woman who presented with the rapid development of multiple dermal and subcutaneous nodules on the chest, back, abdomen, axilla, neck, and scalp. These nodules were firm, tender, and non-ulcerated and measured from 0.2 to 1.2 cm in diameter. A punch biopsy of one of the subcutaneous nodules in the scalp showed a poorly differentiated carcinoma in the reticular dermis with light microscopic, immunohistochemical, and ultrastructural features supporting neuroendocrine differentiation. The past medical history was significant for a recent total abdominal hysterectomy for carcinoma of the cervix at another hospital, originally characterized as a poorly differentiated adenocarcinoma of the cervix and lower uterine segment. Review of the microscopic slides of the uterine neoplasm revealed features suggesting a more appropriate classification as a primary neuroendocrine carcinoma; this was subsequently confirmed by immunophenotyping and ultrastructural evaluation. This is the first reported case of a uterine neuroendocrine carcinoma metastasizing exclusively to the skin. It further illustrates the important contribution of dermatopathology to the understanding of a systemic pathologic process.

Adult↗
PubMed1993

Three downstream sites repress transcription of a Ty2 retrotransposon in Saccharomyces cerevisiae.

Transcription of Ty1 and Ty2 retrotransposons of the yeast Saccharomyces cerevisiae is modulated by multiple downstream regulatory sites. Both transposon families include a positively acting site within the transcribed region which resembles a higher eukaryotic enhancer. We have demonstrated the existence of a repression site distal to the enhancer of the Ty2-917 element. Here we describe experiments investigating the internal structure of this site. We show that this 200-bp region includes three distinct repression sites which we term DRSI (downstream repression site I), DRSII, and DRSIII. Individually each site causes almost twofold repression, and together the sites repress eightfold. Unexpectedly, when the entire region encompassing the DRS sites is moved outside the transcription unit, it acts as a qualitatively positively acting element. In this context the DRS sites still repress transcription, since eliminating them increases transcription further. That the region can activate transcription implies that it includes activation sites in addition to the three repression sites. The change from qualitatively negatively acting to positively acting must reflect a change in the relative effects of the multiple positive and negative sites; when moved outside the transcription unit, the activators predominate. Importantly, DRSII and DRSIII repress transcription autonomously when inserted upstream of a heterologous promoter activated by the transcriptional activator GCN4, showing that they are indeed transcriptional repression sites.

Base Sequence↗
PubMed1993

Altered brain development in Turner's syndrome: an event-related potential study.

We compared event-related brain potentials (ERPs) and reaction time (RT) measures from untreated young (prepubertal and peripubertal; ages 9 to 14) and old (postpubertal; ages 15 to 20) Turner's syndrome (TS) subjects with those from normal age-matched controls. Comparisons among groups permitted the assessment of the relative roles of congenital and maturational brain alterations as possible bases of the cognitive deficits in TS. All subjects were presented with series of auditory stimuli, and they either counted one of the two stimuli or made rapid discriminative button presses to both. The results indicated that, whereas the ERPs in young TS females were essentially the same as those in their age-matched controls, the ERPs in old TS females more closely resembled those in both young groups than those in their age-matched controls. Specifically, a late (400 to 900 msec) frontal negative slow wave (Nc) in the old TS subjects failed to show the normal maturational course in which the amplitude and duration of this component steadily decreases with age. Except for slightly greater amounts of N1 amplitude in the young TS group, the latencies, amplitudes, and scalp distributions of the other ERP components (N1, P2, N2, P300) were all the same at all ages in the TS subjects and their controls. Behaviorally, both TS groups had longer RTs than their controls but, consistent with the ERP results, they did not make more errors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Factors affecting the range of movement of total knee arthroplasty.

We have investigated those factors which influence the range of movement after total knee arthroplasty, including sex, age, preoperative diagnosis and preoperative flexion deformity and flexion range. We also compared cemented and cementless tibial fixation, the influence of collateral ligament and lateral parapatellar releases and of replacement of the patella, and of the period of postoperative immobilisation. We reviewed 516 Johnson-Elloy (Accord) knee arthroplasties performed between 1982 and 1989, with a minimum follow-up of 12 months. The most important factors in the range of flexion achieved after arthroplasty are the diagnosis and the preoperative range of flexion. In patients with osteoarthritis there was a mean loss of flexion; in rheumatoid arthritis there was a mean gain. In both groups, the stiffer knees gained motion and the more mobile knees lost it. Post-operative range of motion was not influenced significantly by cement fixation, collateral ligament or patellar retinacular releases, prolonged immobilisation or patellar replacement.

Age Factors↗