Biomedical subjects

C L Johnson

Publications and source records attributed to C L Johnson.

At least 55 records · Page 3Linked to original sources

PubMed1997

Interictal 99Tc(m) HMPAO SPECT and 1H MRS in children with temporal lobe epilepsy.

PURPOSE: To understand the pathological basis of focal hypoperfusion seen on interictal 99Tc(m) hexamethylpropyleneamine oxime (HMPAO) single-photon-emission computed tomography (SPECT) in intractable temporal lobe epilepsy, and to determine why the technique may be misleading in the localization and lateralization of the seizure focus in some cases. METHODS: Interictal 99Tc(m) HMPAO SPECT and proton magnetic resonance spectroscopy (1H MRS) of the mesial temporal regions were performed in 14 children with intractable temporal lobe epilepsy not caused by a foreign tissue lesion. RESULTS: Hypoperfusion of one temporal lobe ipsilateral to the seizure focus was demonstrated in 10 (71%) of the children; 1H MRS correctly lateralised in eight of these 10. No asymmetry of perfusion of the anterior temporal regions was seen in the remaining four children; on 1H MRS, three of these were bilaterally abnormal but nonlateralising. Repeated SPECT and 1H MRS in three children demonstrated changes over time, the findings from the two techniques being consistent with each other on both the initial and the repeated scans. CONCLUSIONS: Abnormalities demonstrated by 1H MRS correlate well with those seen on interictal SPECT and can help to understand the pathologic basis of these SPECT abnormalities. Furthermore, the presence of bilateral damage can result in an absence of perfusion asymmetry on interictal SPECT.

Adolescent↗

PubMed1997

Diffusion weighted magnetic resonance imaging of compromised tissue in stroke.

Diffusion weighted imaging (DWI) and T2 weighted magnetic resonance imaging were performed on at least two occasions in 28 children presenting with stroke. In previous reports of DWI in human stroke, eventual infarction was observed (with only one exception) in all regions in which early DWI hyperintensity occurred. In the present report, two children had regions of DWI hyperintensity which did not progress to infarction. One patient who presented with right hemiplegia showed extensive high signal on DWI, with T2 evidence of tissue swelling but without hyperintensity. DWI changes persisted over weeks, with no imaging indication of infarction. This child recovered completely. A second child who had a major vessel infarct with concomitant regions of hyperintensity on T2 weighted imaging and DWI, also had DWI hyperintensity in an adjacent territory which did not develop any subsequent evidence of infarction. Thus in clinical practice DWI can demonstrate tissue which is compromised but not irreversibly so.

Brain↗

PubMed1997

Mutational analysis of Glu-327 of Na(+)-K(+)-ATPase reveals stimulation of 86Rb+ uptake by external K+.

A competition assay of 86Rb+ uptake in HeLa cells transfected with ouabain-resistant Na(+)-K(+)-ATPase mutants revealed a stimulation of 86Rb+ uptake at low external concentrations (1 mM) of competitor (K+). Of the models that were tested, those that require that two K+ be bound before transport occurs gave the worst fits. Random and ordered binding schemes described the data equally well. General models in which both binding and transport were allowed to be cooperative yielded parameter errors larger than the parameters themselves and could not be utilized. Models that assumed noncooperative transport always showed positive cooperativity in binding. E327Q and E327L mutated forms of rat alpha 2 had lower apparent affinities for the first K+ bound than did wild-type rat alpha 2 modified to be ouabain resistant. The mutations did not affect the apparent affinity of the second K+ bound. Models that assumed noncooperativity in binding always showed positively cooperative transport, i.e., enzymes with two K+ bound had a higher flux than those with one K+ bound. Increases in external Na+ decreased the apparent affinity for K+ for all models and decreased the ratio of the apparent influx rate constants for E327L.

Amino Acid Substitution↗

PubMed1997

Prevalence of overweight among preschool children in the United States, 1971 through 1994.

OBJECTIVE: To examine the prevalence of overweight among US preschool children 2 months through 5 years of age between the years 1971 through 1974 and 1988 through 1994. DESIGN: Nationally representative cross-sectional surveys with a physical examination, including measurement of stature, length, and weight. Between 1200 and 7500 children younger than 6 years were examined in each of four different surveys during 1971 through 1974 (first National Health and Nutrition Examination Survey [NHANES I]), 1976 through 1980 (NHANES II), 1982 through 1984 (Hispanic Health and Nutrition Examination Survey), and 1988 through 1994 (NHANES III). RESULTS: The prevalence of overweight increased among some sex and age groups of preschool children between 1971 through 1974 and 1988 through 1994. More than 10% of 4- and 5-year-old girls were overweight in 1988 through 1994 compared with 5.8% in 1971 through 1974. However, there was no change during this period in the prevalence of overweight among 1- and 2- to 3-year-old children. During 1988 through 1994, the prevalence of overweight among children 2 months through 5 years of age was consistently higher in girls than boys. Mexican-American children had a higher prevalence of overweight than non-Hispanic black and non-Hispanic white children. These results parallel what has been reported for older children and adults in the United States. CONCLUSION: These results show that in the last 20 years the prevalence of overweight has increased among 4- and 5-year-old children but not among younger children. These findings suggest that efforts to prevent overweight, including encouragement of physical activity and improved diets, should begin in early childhood.

Body Height↗

PubMed1997

Apolipoprotein B and AI distributions in the United States, 1988-1991: results of the National Health and Nutrition Examination Survey III (NHANES III).

Serum apolipoproteins (apo) B and AI were measured in a probability sample of the noninstitutionalized US civilian population, ages > or = 4 years, which included non-Hispanic whites, non-Hispanic blacks, and Mexican-Americans. Apo B concentrations were the same in males and females, lower in black males than in other males, low in childhood (approximately 0.80 g/L) and increasing to approximately 1.2 g/L in adults, and higher in younger women on hormones. Apo AI was higher in females than males, higher in blacks than in others, remained constant from childhood to adulthood (approximately 1.35 g/L) in males, but increased with age (approximately 1.30 g/L to approximately 1.55 g/L) in females, and was higher in women taking hormones. These are the first national probability estimates of apo B and apo AI in the US and are referable to the WHO-IFCC First International Reference Materials for apo AI and B.

Adolescent↗

PubMed1996

A 1.5-megabase physical map encompassing the multiple endocrine neoplasia type-1 (MEN1) locus on chromosome 11q13.

Linkage analysis and loss of heterozygosity studies have shown that the gene responsible for the multiple endocrine neoplasia type-1 (MEN1) syndrome localizes to a small interval between D11S427 and D11S460 on chromosome 11q13. As an initial step to clone this tumor suppressor gene, our group is the first to map the MEN1 region physically using yeast artificial chromosome, bacterial artificial chromosome (BAC), and cosmid contigs. The 1.5-Mb high-resolution, contiguous map extends from PYGM to 300 kb telomeric of D11S460. Of this, the 1.2-Mb interval between PYGM and D11S460 is isolated in cosmids and BACs and will be useful for the development of genomic sequences and transcription maps of this important region. Nine new sequence-tagged sites (STS) are also characterized from this region. The physical map and the STSs will be valuable tools for the cloning of the MEN1 gene.

Chromosome Mapping↗

PubMed1996

Proton magnetic resonance spectroscopy in children with temporal lobe epilepsy.

We performed proton magnetic resonance spectroscopy of the mesial temporal regions in 20 children with intractable temporal lobe epilepsy and compared results with those from 13 normal subjects. Abnormalities of the ratio of N-acetylaspartate to choline plus creatine (NAA/[Cho+Cr]) were seen in 15 patients (75%). The ratio NAA/(Cho+Cr) was correctly lateralizing in 55% and incorrectly lateralizing in none. Bilateral abnormalities were seen in 45%. Overall there was a unilateral decrease in N-acetylaspartate on the side ipsilateral to the seizure focus (mean 19% decrease vs normals, with 5% decrease on the contralateral side), suggesting neuronal loss or dysfunction. There was also a bilateral increase in creatine and choline (mean 18%), consistent with reactive astrocytosis. We conclude that proton magnetic resonance spectroscopy can contribute to lateralization of the seizure focus, and by detection of bilateral abnormalities, can contribute to the understanding of the underlying pathophysiology in temporal lobe epilepsy.

Adolescent↗

PubMed1996

Multimodal management of diffuse neonatal hemangiomatosis.

Diffuse neonatal hemangiomatosis is a rare, frequently fatal disorder. We describe the case of a neonate with numerous cutaneous and ocular hemangiomas. Hepatic hemangiomas were noted at 4 weeks of age, associated with congestive heart failure resulting from hepatic arteriovenous shunting. This condition was controlled by treatment with prednisone, interferon alfa-2b and hepatic embolization. Treatment of cutaneous hemangiomas with the tunable dye laser prevented hemorrhage, facilitated routine skin care, and allowed uninhibited intravenous access during hospitalization.

Antineoplastic Agents↗

PubMed1996

Working with difficult-to-treat eating disorders using an integration of twelve-step and traditional psychotherapies.

In summary, we have a multidimensional treatment program that attempts to integrate psychodynamic, cognitive-behavioral, systemic, psychopharmacologic, and 12-step interventions. For patients who have not had previous treatments or patients who are young adolescents, we do not emphasize the 12-step approach. For our difficult-to-treat patients, our current overall impression is that the benefits of adding the 12-step component have outweighed the costs. We began the program with an expressed intent of experimenting with the integration. Staff were subsequently recruited who were open to the experiment and the success of the integration has been a function of the flexibility within the staff. Our hunch is that this integration would not work as well with an existing staff who harbored prejudice toward either position. Actually, we have found working on the integration quite invigorating. Our recovering counselors have raised issues that we have not heard raised in the more traditional settings we have been associated with. Likewise, we have seen our counselors grow professionally from hearing alternative views of why individuals struggle and how they get better. The exchange has been synergistic rather than divisive. Although we are encouraged by our early experience, it is the long-term outcome that will clarify the relative usefulness of this treatment strategy. We are confident that as we live with the integration longer, more of the advantages and disadvantages will become apparent and perhaps we can refine our understanding of which subgroup of patients makes most use of this type of integrated approach.

Feeding and Eating Disorders↗

PubMed1996

Regaining self-esteem: strategies and interventions for the infertile woman.

Infertility can cause women to lose their sense of power and control, thus diminishing their self-esteem. Terminology, technology, and testing may contribute to this sense of failure. Nurses can intervene by recognizing this negative consequence of infertility and using strategies within the nursing model.

Family Planning Services↗

PubMed1996

The amygdala and intractable temporal lobe epilepsy: a quantitative magnetic resonance imaging study.

OBJECTIVE: To establish a quantitative MRI technique using T2 relaxation time mapping to study systematically the amygdala in patients with intractable temporal lobe epilepsy (TLE). BACKGROUND: Identification of a focal abnormality on MRI in patients with intractable TLE is important, because outcome from surgery depends largely on the removal of the underlying pathology. Hippocampal sclerosis (HS) is the most common cause of intractable TLE, but epileptogenic lesions can be confined to the amygdala. METHODS: Twenty control subjects and 82 patients with intractable TLE were studied. Patients who had foreign tissue lesions visible on routine MRI were excluded. All subjects had a hippocampal T2 map and volumetry and an amygdala T2 (AT2) map. RESULTS: Forty-four of the 82 patients (54%) had an abnormal AT2, which was bilateral in 18. Forty-four patients (54%) had unilateral HS on MRI, 25 (57%) of whom had an abnormal AT2. Seven patients (8%) had bilateral HS, four of whom had an abnormal AT2. Thirty-one patients (38%) had normal quantitative hippocampal measures, 15 of whom had an abnormal AT2, which was bilateral in seven. Fluid attenuated inversion recovery (FLAIR) imaging, where appropriate, confirmed that the increased AT2 signal was due to parenchymal changes. Neuropathologic correlates of an increased AT2 included microdysgenesis in one and gliosis in three patients. Patients with an isolated AT2 abnormality were significantly older at the onset of habitual epilepsy and rarely had a history of febrile convulsions, in comparison with patients who had HS. An isolated AT2 abnormality correlated well with interictal EEG findings. CONCLUSIONS: The combination of AT2 mapping and FLAIR is a sensitive method to detect lesions that are not seen on routine MRI in the amygdalae of patients with intractable TLE. Further correlational studies will be required to define the role of this technique in the presurgical evaluation of patients with intractable TLE.

Adolescent↗

PubMed1996

The use of ondansetron in the treatment of nausea and vomiting associated with acetaminophen poisoning.

BACKGROUND: Nausea and vomiting associated with poisoning can complicate treatment and in some cases delay potential antidote administration. Side effect such as lowering the seizure threshold may at times discourage the use of traditional phenothiazine and butyrophenone antiemetics. METHODS: We performed a prospective, single arm, observational study examining the effectiveness of the 5HT3 receptor antagonist ondansetron in the management if nausea and vomiting associated with acetaminophen poisoning. Patients with a history or laboratory evidence of acetaminophen poisoning were eligible for inclusion in the study. Exclusion criteria included age less than 18 or greater than 65, use of other antiemetic therapy within the previous 12 hours, history of preexisting hepatic or hematologic disease, pregnancy, or significant ingestion of other substances. Upon meeting entry criteria, patients were administered 8 mg of intravenous ondansetron. Nausea was graded on a 100 mm scale with number of emetic episodes recorded before and after treatment. RESULTS: Six patients were entered in the study. All patients had nausea and at least one emetic episode prior to ondansetron and prior to administration of N-acetylcysteine. All patients reported relief of nausea after ondansetron. The degree of nausea decreased by an average of 52% at 30 min and 88% at 60 min following ondansetron administration. No significant vital sign changes were recorded in any patient, and there were no complications related to therapy. Three patients were administered N-acetylcysteine, and all tolerated this therapy without vomiting after ondansetron. CONCLUSIONS: Ondansetron appears to be a potentially useful adjunct in the management of nausea and vomiting associated with acetaminophen poisoning.

Acetaminophen↗

PubMed1995

Amino acid replacement of Asp369 in the sheep alpha 1 isoform eliminates ATP and phosphate stimulation of [3H]ouabain binding to the Na+, K(+)-ATPase without altering the cation binding properties of the enzyme.

Modification of aspartic acid 369 in the sheep alpha 1 Na+,K(+)-ATPase to asparagine results in a membrane-associated form of Na+,K(+)-ATPase that can bind [3H]ouabain with high affinity in the presence of Mg2+ alone (KD = 20.4 +/- 2.6 nM). Ouabain binding to the D369N mutant is not stimulated by inorganic phosphate, confirming that Asp369 is both the catalytic phosphorylation site and the only Pi interaction site which stimulates ouabain binding. Cation inhibition of Mg(2+)-stimulated ouabain binding to the D369N mutant demonstrated that three Na+ and two K+ ions inhibit [3H]ouabain binding and suggests that this inhibition must occur via a cation-sensitive conformational change which does not directly involve dephosphorylation of the enzyme. In the presence of 10 mM Mg2+, ATP stimulates ouabain binding to the wild type protein, (AC50 = 21.4 +/- 2.7 microM) but inhibits the binding to the D369N mutant (IC50 = 2.52 +/- 0.17 microM) indicating that the mutation does not destroy the high affinity site for MgATP but does change the nature of the protein conformation normally induced by a nucleotide-Na+,K(+)-ATPase interaction. Increasing the Mg2+ from 1 to 10 mM did not alter the AC50 or IC50 values for ATP and reveals that the Mg2+ interaction which stimulates ouabain binding in the absence of nucleotide involves a distinct divalent cation site not associated with the binding of the magnesium-nucleotide complex. Thus, altering the catalytic phosphorylation site of Na+,K(+)-ATPase does not affect the expression of the ouabain-sensitive protein in the membrane fraction of NIH 3T3 cells and does not disrupt the binding of Na+, K+, Mg2+, ouabain, or ATP to the enzyme. However, the D369N substitution does inhibit the formation of a nucleotide-protein complex with high affinity for ouabain.

Adenosine Triphosphate↗

PubMed1995

Glutamic acid 327 in the sheep alpha 1 isoform of Na+,K(+)-ATPase is a pivotal residue for cation-induced conformational changes.

The cation binding characteristics of the mutant E327A formed in the sheep alpha 1 isoform of the Na+,K(+)-ATPase were examined using [3H]ouabain binding as a function of monovalent cation concentrations. Equilibrium competition binding assays in the presence of Mg2+, inorganic phosphate and various amounts of unlabelled ouabain indicated that both wild-type sheep alpha 1 protein and the E327A mutant expressed in 3T3 cells had similar affinities for ouabain (KD = 1.53 and 1.31 nM respectively). Sodium inhibition of ouabain binding appeared competitive in both enzymes. However, binding of three Na+ ions was required to explain the steep character of the Na+ inhibition curve for the wild-type Na+,K(+)-ATPase (Ki = 12.8 +/- 1.6 mM), whereas the binding of two Na+ ions was detected for the mutant E327A (Ki = 19.2 +/- 2.5 mM). Potassium binding of [3H]ouabain binding displayed a partially competitive nature with Hill coefficients of 2 for both wild-type sheep alpha 1 (Ki = 0.743 +/- 0.044 mM) and E327A (Ki = 0.875 +/- 0.067 mM). At concentrations of K+ above 10 mM, the sheep alpha 1 competition curve levelled off whereas the inhibition curve for E327A displayed a stimulation in ouabain binding. This stimulation in [3H]ouabain binding also occurred with Rb+, Cs+ and Li+, but was never observed with choline or Na+, suggesting that this effect was not due to ionic strength. From these [3H]ouabain-binding studies, it is obvious that the mutant enzyme E327A in the presence of Mg2+, Pi and ouabain, interacts with monovalent cations in a unique fashion. One interpretation of these data is that the glutamic acid residue at position 327 is involved in a conformational transition induced by the binding of monovalent cations to the Na+,K+-ATPase and that this transition is inhibited by the mutation of E327A.

3T3 Cells↗

PubMed1995

Comparison of the effects of potassium on ouabain binding to native and site-directed mutants of Na,K-ATPase.

We examined the effect of K+ on Mg(2+)- and P(i)-supported [3H]ouabain binding to Na,K-ATPases, including partially purified enzyme from sheep kidney and wild-type and mutant sheep alpha 1 isoforms (C104A, Y108A, E116Q, P118K, Y124F, R880P, R880L, and N122D) expressed in NIH3T3 cells. In the presence of increasing concentrations of K+, [3H]ouabain binding to these enzymes decreases but never reaches nonspecific binding levels, consistent with the concept that ouabain is still able to bind to the K(+)-complexed enzyme but with reduced affinity. A partially competitive model for K+ inhibition of ouabain binding is proposed which satisfactorily fits the binding data. The model is consistent with the sequential binding of two K+ ions to the enzyme. Ki values (approximately 1.0 mM) for K+ obtained from this model are comparable to the apparent K+ affinities of the rat alpha isoforms determined by measuring the K+ dependence of Na,K-ATPase activity [E. A. Jewell and J. B. Lingrel (1991) J. Biol. Chem. 266, 16925-16930]. This is consistent with the concept that K+ inhibition of Mg2+ plus P(i) supported ouabain binding is mediated by K+ binding to the same high-affinity binding sites present in the native enzyme under physiological conditions. While the mutants exhibit binding constants for ouabain which vary more than 30-fold from that of the wild-type enzyme, their affinities for K+ differ less than twofold from that of the native enzyme. Our results suggest that the ouabain and K+ binding sites are not the same and are differentially affected by mutations of the enzyme. The system described here should prove useful in the analysis of cation binding to other mutants of the Na,K-ATPase, especially those carrying amino acid replacements which result in an inactive enzyme.

3T3 Cells↗

PubMed1995

Glutamic acid 327 in the sheep alpha 1 isoform of Na+,K(+)-ATPase stabilizes a K(+)-induced conformational change.

By combining the tools of site-directed mutagenesis and [3H]ouabain binding, the functional role of glutamic acid 327 in the fourth transmembrane domain of the sheep alpha 1 isoform of Na+,K(+)-ATPase was examined with respect to its interactions with ouabain, Na+,K+,Mg2+, and inorganic phosphate. Using site-directed mutagenesis, this glutamic acid was substituted with alanine, aspartic acid, glutamine, and leucine. The mutant proteins were constructed in a sheep alpha 1 protein background such that [3H]ouabain binding could be utilized as a highly specific probe of the exogenous protein expressed in NIH 3T3 cells. Na+ competition of [3H]ouabain binding to the mutant forms of Na+,K(+)-ATPase revealed only slight alterations in their affinities for Na+ and in their abilities to undergo Na(+)-induced conformational changes which inhibit ouabain binding. In contrast, K+ competition of [3H]ouabain binding to all four mutant forms of Na+,K(+)-ATPase displayed severely altered interactions between these proteins and K+. Interestingly, [3H]ouabain binding to the mutant E327Q was not inhibited by the presence of K+. This mutant was previously reported to be functionally able to support cation transport with a 5-fold reduced K0.5 for K(+)-dependent ATPase activity (Jewell-Motz, E. A., and Lingrel, J.B. (1993) Biochemistry 32, 13523-13530; Vilsen, B. (1993) Biochemistry 32, 13340-13349). Thus, it appears that this glutamic acid in the fourth transmembrane domain may be important for stabilizing a K(+)-induced conformation within the catalytic cycle of Na+,K(+)-ATPase that is not rate-limiting in the overall ATPase cycle but that displays a greatly reduced affinity for ouabain.

3T3 Cells↗

PubMed1995

Overweight prevalence and trends for children and adolescents. The National Health and Nutrition Examination Surveys, 1963 to 1991.

OBJECTIVE: To examine prevalence of overweight and trends in overweight for children and adolescents in the US population. DESIGN: Nationally representative cross-sectional surveys with an in-person interview and a medical examination, including measurement of height and weight. PARTICIPANTS: Between 3000 and 14,000 youths aged 6 through 17 years examined in each of five separate national surveys during 1963 to 1965, 1966 to 1970, 1971 to 1974, 1976 to 1980, and 1988 to 1991 (Cycles II and III of the National Health Examination Survey, and the first, second, and third National Health and Nutrition Examination Surveys, respectively). MAIN OUTCOME MEASURES: Prevalence of overweight based on body mass index and 85th or 95th percentile cutoff points from Cycles II and III of the National Health Examination Survey. RESULTS: From 1988 to 1991, the prevalence of overweight was 10.9% based on the 95th percentile and 22% based on the 85th percentile. Overweight prevalence increased during the period examined among all sex and age groups. The increase was greatest since 1976 to 1980, similar to findings previously reported for adults in the United States. CONCLUSIONS: Increasing overweight among youths implies a need to focus on primary prevention. Attempts to increase physical activity may provide a means to address this important public health problem.

Adolescent↗

PubMed1995

Total energy intake of the US population: the third National Health and Nutrition Examination Survey, 1988-1991.

The third National Health and Nutrition Examination Survey (NHANES III) was conducted to assess the health and nutritional status of the US population. As part of the nutritional status assessment, reliable 24-h dietary recalls were collected for 14,801 examined persons. Mean (+/- SEM) energy intakes are reported for persons aged > or = 2 mo by age, sex, and race-ethnicity. Males had higher mean energy intakes than did females. Energy intakes peaked during late adolescence and young adulthood and declined thereafter. Energy intake patterns were similar among non-Hispanic whites, non-Hispanic blacks, and Mexican Americans. Underreporting was addressed by computing a ratio of energy intake (EI) to estimated basal metabolic rate (BMRest). This ratio (EI:BMRest) was 1.47 for adult males and 1.26 for nonpregnant adult females. Overweight adults had a lower mean EI:BMRest (1.09 in females and 1.28 in males). Underreporting in food consumption surveys remains problematic among females and overweight persons.

Adolescent↗