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K M Johnson

Publications and source records attributed to K M Johnson.

At least 55 records · Page 3Linked to original sources
PubMed1999

N-phenylalkyl-substituted tropane analogs of boat conformation with high selectivity for the dopamine versus serotonin transporter.

A series of N-phenylalkyl-substituted tropane analogs of boat conformation was synthesized, and these tropanes were evaluated for their ability to inhibit high affinity uptake of dopamine (DA) and serotonin (5-HT) into striatal nerve endings (synaptosomes). Some of these compounds exhibit high affinity for the DA transporter with a 5-HT/DA transporter selectivity ratio of >50.

Carrier Proteins↗
PubMed1999

Synthesis and biological evaluation of two novel DAT-binding technetium complexes containing a piperidine based analogue of cocaine.

Two new technetium complexes containing a piperidine template have been synthesized and evaluated as possible leads for the development of dopamine transporter (DAT) imaging agents. Binding data for the corresponding rhenium complexes containing either a monoaminomonoamide (MAMA') or a diaminodithiol (DADT) chelating unit exhibited significant affinity for the DAT. Initial biodistribution studies in rats revealed only a low brain uptake.

Animals↗
PubMed1999

Regulation of NMDA-stimulated [14C]GABA and [3H]acetylcholine release by striatal glutamate and dopamine receptors.

Striatal function is heavily influenced by glutamatergic and dopaminergic afferent input. To ultimately better understand how the N-methyl-D-aspartate (NMDA) antagonist, phencyclidine (PCP), alters striatal function, we sought to determine how NMDA receptor function is influenced by activation of other glutamatergic receptors and by dopaminergic receptors. To this end, we used NMDA-stimulated efflux of [14C]GABA and [3H]acetylcholine (ACh) from striatal slices to assess the influence of these receptors on NMDA function. NMDA-stimulated [14C]GABA release was more sensitive to NMDA and glycine antagonists than was [3H]ACh release, suggesting that different NMDA receptors regulate the release of these neurotransmitters. Furthermore, NMDA-stimulated [3H]ACh release was inhibited by a D2 receptor mechanism whereas NMDA-stimulated [14C]GABA release was enhanced by D1 receptor activation. NMDA and (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid hydrobromide (AMPA) interact additively to evoke [3H]ACh release, and synergistically to evoke [14C]GABA release. An additive effect of NMDA and kainate (KA) was found on [14C]GABA release, but NMDA and KA acted in a less than additive manner in evoking [3H]ACh release. KA-stimulated [3H]ACh release was largely blocked by NMDA antagonists, suggesting mediation through activation of NMDA receptors, probably secondary to KA-induced glutamate release. A selective group II metabotropic receptor agonist inhibited NMDA-stimulated [14C]GABA and [3H]ACh release. On the other hand, NMDA-stimulated [14C]GABA release was potentiated by activation of group I metabotropic receptors. Thus, in addition to the differential modulation by D1- and D2-like receptors, the release of striatal neurotransmitters by NMDA receptor activation depends on the extent to which the other glutamate receptors, both ionotropic and metabotropic, are activated.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1999

Synthesis of 8-Oxa analogues of norcocaine endowed with interesting cocaine-like activity.

In order to further explore the importance of cocaine's bridge nitrogen atom in binding to the dopamine transporter (DAT), we have synthesized the previously known racemic 8-oxa-norcocaines 3-6 in which the nitrogen atom has been replaced by oxygen. Additionally, to avoid incorrect interpretations of biological data that may stem from the use of racemic materials, several of these analogues were synthesized and tested in non-racemic form. (-)-8-Oxa-norcocaine (3) was found to bind to the cocaine recognition site and to inhibit the dopamine transporter with potencies only about 8-fold and 4-fold, respectively, less than those of norcocaine (2). (-)-8-Oxa-pseudonorcocaine (4) as well as (+)-8-oxa-norcocaine (3) were found to be comparable in activity to (-)-oxa-norcocaine. These pharmacological findings support our earlier suggestion that cocaine is likely to bind in its neutral form to the DAT.

Carrier Proteins↗
PubMed1999

Molecular analysis of the ERGIC-53 gene in 35 families with combined factor V-factor VIII deficiency.

Combined factor V-factor VIII deficiency (F5F8D) is a rare, autosomal recessive coagulation disorder in which the levels of both coagulation factors V and VIII are diminished. The F5F8D locus was previously mapped to a 1-cM interval on chromosome 18q21. Mutations in a candidate gene in this region, ERGIC-53, were recently found to be associated with the coagulation defect in nine Jewish families. We performed single-strand conformation and sequence analysis of the ERGIC-53 gene in 35 F5F8D families of different ethnic origins. We identified 13 distinct mutations accounting for 52 of 70 mutant alleles. These were 3 splice site mutations, 6 insertions and deletions resulting in translational frameshifts, 3 nonsense codons, and elimination of the translation initiation codon. These mutations are predicted to result in synthesis of either a truncated protein product or no protein at all. This study revealed that F5F8D shows extensive allelic heterogeneity and all ERGIC-53 mutations resulting in F5F8D are "null." Approximately 26% of the mutations have not been identified, suggesting that lesions in regulatory elements or severe abnormalities within the introns may be responsible for the disease in these individuals. In two such families, ERGIC-53 protein was detectable at normal levels in patients' lymphocytes, raising the further possibility of defects at other genetic loci.

Algeria↗
PubMed1999

Antifactor VIII antibody inhibiting allogeneic but not autologous factor VIII in patients with mild hemophilia A.

Two unrelated patients with the same Arg2150His mutation in the factor VIII (FVIII) C1 domain, a residual FVIII activity of 0.09 IU/mL, and inhibitor titres of 300 and 6 Bethesda Units, respectively, were studied. Further analysis of patient LE, with the highest inhibitor titer, showed that (1) plasma or polyclonal IgG antibodies prepared from LE plasma inhibited the activity of allogeneic (wild-type) but not of self FVIII; (2) the presence of von Willebrand factor (vWF) increased by over 10-fold the inhibitory activity on wild-type FVIII; (3) the kinetics of FVIII inhibition followed a type II pattern, but in contrast to previously described type II inhibitors, LE IgG was potentiated by the presence of vWF instead of being in competition with it; (4) polyclonal LE IgG recognized the FVIII light chain in enzyme-linked immunosorbent assay and the recombinant A3-C1 domains in an immunoprecipitation assay, indicating that at least part of LE antibodies reacted with the FVIII domain encompassing the mutation site; and (5) LE IgG inhibited FVIII activity by decreasing the rate of FVIIIa release from vWF, but LE IgG recognized an epitope distinct from ESH8, a murine monoclonal antibody exhibiting the same property. We conclude that the present inhibitors are unique in that they clearly distinguish wild-type from self, mutated FVIII. The inhibition of wild-type FVIII by LE antibody is enhanced by vWF and is associated with an antibody-dependent reduced rate of FVIIIa release from vWF.

Amino Acid Substitution↗
PubMed1999

Chronic phencyclidine increases NMDA receptor NR1 subunit mRNA in rat forebrain.

The present study was designed to determine whether the sensitization of locomotor activity that results from chronic phencyclidine (PCP) administration is associated with altered NMDA receptor function or mRNA in rat brain. Female Sprague-Dawley rats were administered PCP (20 mg/kg, i.p.) once daily for 5 days. After withdrawal for 72 hr, challenge with 3.2 mg/kg PCP (i.p.) revealed a significant sensitization to the locomotor activating effect of PCP. In situ hybridization analysis with an oligonucleotide probe complementary to the mRNA encoding the NR1 subunit of the NMDA receptor demonstrated that chronic PCP treatment resulted in a marked increase in NR1 subunit mRNA in the forebrain. Quantitative image analysis revealed a significant increase in the labeling of NR1 mRNA in the olfactory tubercle, piriform cortex, frontal cortex, and anterior striatum. However, no significant difference between PCP and saline-treated rats was found in the hippocampus or cerebellum. In a parallel study, possible functional alterations in the NMDA receptor were assessed by measuring NMDA-stimulated release of [3H]DA from slices of the olfactory tubercle and piriform cortex. NMDA-stimulated release was not affected by chronic PCP treatment, but the inhibition of this release by PCP, 7-chlorokynurenic acid (7-CK), and DL-2-amino-5-phosphovaleric acid (AP-5) was significantly diminished by chronic PCP. This suggests that the behavioral plasticity associated with chronic PCP may be related to an altered subunit stoichiometry of NMDA receptors in selective forebrain regions.

Animals↗
PubMed1999

Augmentation of locomotor activity by chronic phencyclidine is associated with an increase in striatal NMDA receptor function and an upregulation of the NR1 receptor subunit.

Phencyclidine (PCP) is a drug of abuse that produces schizophrenia-like symptoms in humans and increases locomotor activity and stereotypic behavior in rodents. PCP-induced alteration in rat locomotor activity is thought to be mediated by an inhibition of N-methyl-D-aspartate (NMDA) receptors in the striatum and other brain regions. In this study, rats treated chronically with PCP (20 mg/kg once per day for 5 days) showed a marked increase in locomotor activity following a PCP challenge (3.2 mg/kg) administered after either 3 or 8 days of withdrawal. In biochemical assays, the release of striatal [14C]GABA by NMDA was enhanced by about 77% by chronic PCP treatment, whereas [3H]ACh release was increased by about 31% in tissue from PCP-treated rats. Even though binding experiments with 1-[1-(2-thiethyl)cyclohexyl]piperidyl-3,4 3H(N) ([3H]TCP) showed no alteration in the Kd or Bmax in whole striatum, quantitative immunocytochemical experiments found an upregulation in the NR1 subunit in the cell bodies and neuropil of cortical and striatal regions of the forebrain following chronic PCP treatment. An increase in the size of NR1-immunoreactive cells in the forebrain was also observed following chronic PCP treatment. Together, these data may help in understanding the mechanisms underlying the adaptive response to chronic reduction in glutamatergic NMDA transmission that has been postulated to be involved in the etiology of schizophrenia.

Animals↗
PubMed1999

Wavelet packet denoising of magnetic resonance images: importance of Rician noise at low SNR.

Wavelet packet analysis is a mathematical transformation that can be used to post-process images, for example, to remove image noise ("denoising"). At a very low signal-to-noise ratio (SNR <5), standard magnitude magnetic resonance images have skewed Rician noise statistics that degrade denoising performance. Since the quadrature images have approximately Gaussian noise, it was postulated that denoising would produce better contrast and sharper edges if performed before magnitude image formation. Signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and edge blurring effects of these two approaches were examined in synthetic, phantom, and human MR images. While magnitude and complex denoising both significantly improved SNR and CNR, complex denoising yielded sharper edges and better low-intensity feature contrast.

Artifacts↗
PubMed1999

Imaging of thoracic aortic disease.

Computed tomography, magnetic resonance imaging, and transesophageal echocardiography represent the relatively noninvasive techniques available for imaging thoracic aortic disease, especially in the evaluation of aneurysms and dissections. The article discusses the technique and application of these modalities in the evaluation of thoracic aorta. Imaging appearances of the commonly encountered pathologies of the thoracic aorta are presented and discussed, and potential pitfalls of technique and diagnosis are addressed.

Aortic Dissection↗
PubMed1999

The two by two diagram: a graphical truth table.

The two by two table is widely used in statistics, and in particular in the medical literature, to present the results of experimental and clinical studies in which two different operators (such as a reference standard and a new diagnostic test) sort a sample into two groups. The four cells of the table reflect the four possible categories of results. Despite the simplicity of the table, the interplay of its contents is surprisingly complex, and description of this interplay can be confusing if rendered with the conventional descriptive terms alone, such as sensitivity and predictive value. We present a graphical transformation of the table, comprised of a rectangular box in a special coordinate system. This diagram is offered as a flexible and subtle conceptual tool to help physicians, authors, and students to understand, plan, and present clinical research studies.

Data Display↗
PubMed1999

A clinic-based mammography intervention targeting inner-city women.

OBJECTIVE: The objective was to evaluate the effect of a clinic-based intervention program on mammography use by inner-city women. DESIGN: A randomized controlled trial employing firm system methodology was conducted. SETTING: The study setting was a general internal medicine clinic in the university-affiliated county hospital serving metropolitan Seattle. PARTICIPANTS: Women aged 50 to 74 years with at least one routine clinic appointment (when they were due for mammography) during the study period were enrolled in the trial (n = 314). INTERVENTIONS: The intervention program emphasized nursing involvement and included physician education, provider prompts, use of audiovisual and printed patient education materials, transportation assistance in the form of bus passes, preappointment telephone or postcard reminders, and rescheduling assistance. Control firm women received usual care. MEASUREMENTS AND MAIN RESULTS: Mammography completion within 8 weeks of clinic visits was significantly higher among intervention (49%) than control (22%) firm women (p < .001). These effects persisted after adjustment for potential confounding by age, race, medical insurance coverage, and previous mammography experience at the hospital (odds ratio 3.5; 95% confidence interval 1.9, 6.5). The intervention effect was modified by type of insurance coverage as well as prior mammography history. Process evaluation indicated that bus passes and rescheduling efforts did not contribute to the observed increases in screening participation. CONCLUSIONS: A clinic-based program incorporating physician education, provider prompts, patient education materials, and appointment reminders and emphasizing nursing involvement can facilitate adherence to breast cancer screening guidelines among inner-city women.

Adult↗
PubMed1999

Enhancing Cancer Pain Control among American Indians (ECPCAI): a study of the Ojibwe of Minnesota.

BACKGROUND AND OBJECTIVES: This study addressed one American Indian group's experience with cancer, its associated pain, and the resulting barriers in cancer pain management (CPM). METHODS: The project researched the identified problems and implemented solutions. Focus groups at four reservations with clinic personnel and tribal elders reviewed culturally specific experiences and barriers to CPM. Culturally sensitive brochures for patients and guidelines for providers were developed, and health care providers participated in CME sessions. RESULTS: Ojibwe elders report pain when it is >6 (1-10 scale), believe pain always accompanies cancer, and do not believe it can be relieved, although traditional healers can help. They also have addiction concerns. Developed materials changed knowledge (pre-post tests, p = 0.000) and are culturally sensitive (> 92% agreement). CONCLUSION: Medically sound CPM for this population can also be culturally sensitive.

Aged↗
PubMed1999

A search for Ebola virus in animals in the Democratic Republic of the Congo and Cameroon: ecologic, virologic, and serologic surveys, 1979-1980. Ebola Virus Study Teams.

More than 30 years after the first outbreak of Marburg virus disease in Germany and Yugoslavia and 20 years after Ebola hemorrhagic fever first occurred in central Africa, the natural history of filoviruses remains unknown. In 1979 and 1980, animals in the Democratic Republic of the Congo and Cameroon were collected during the dry season near the site of the 1976 Ebola hemorrhagic fever epidemic. The study objectives were to identify local animals and search for evidence of Ebola virus in their tissues. A total of 1664 animals representing 117 species was collected, including >400 bats and 500 rodents. Vero and CV-1 cells and IFA and RIA were used for virus and antibody detection, respectively. No evidence of Ebola virus infection was found. This study was limited in time and animal collections and excluded insects and plants. Long-term, prospective, multidisciplinary comparative studies will yield more information than will repeat short forays on the ecology of filoviruses.

Animals↗
PubMed1999

Herpes simplex virus transactivator VP16 discriminates between HCF-1 and a novel family member, HCF-2.

Herpes simplex virus infection is initiated by VP16, a viral transcription factor that activates the viral immediate-early (IE) genes. VP16 does not recognize the IE gene promoters directly but instead forms a multiprotein complex with Oct-1 and HCF-1, a ubiquitous nuclear protein required for progression through the G1 phase of the cell cycle. The functional significance of recruiting HCF-1 to the VP16-induced complex is not understood. Here we describe the identification of a second HCF-like protein, designated HCF-2. HCF-2 is smaller than HCF-1 but shares three regions of strong amino acid sequence homology, including the beta-propeller domain required for association with VP16. HCF-2 is expressed in many tissues, especially the testis, and shows a more dynamic pattern of subcellular localization than HCF-1. Although HCF-2 associates with VP16 and can support complex assembly with Oct-1 and DNA, it is significantly less efficient than HCF-1. A similar preference is shown by LZIP, a cellular counterpart of VP16. Analysis of chimeric proteins showed that differences between the fifth and sixth kelch repeats of the beta-propeller domains from HCF-1 and HCF-2 dictate this selectivity. These results reveal an unexpected level of specificity in the recruitment of HCF-1 to the VP16-induced complex, paralleling the preferential selection of Oct-1 rather than the closely related POU domain protein Oct-2. Implications for regulation of the viral life cycle are discussed.

Amino Acid Sequence↗
PubMed1999

Total-body echo-planar MR imaging in the staging of breast cancer: comparison with conventional methods--early experience.

PURPOSE: To test breast cancer staging with total-body echo-planar magnetic resonance (MR) imaging. MATERIALS AND METHODS: Nineteen patients with newly diagnosed breast cancer were imaged by using a 1.5-T echo-planar MR system. By using a table sweep method, 180 contiguous axial images were obtained from the cranial vertex through the feet with T2-weighted spin-echo and inversion-recovery sequences. Results were compared with those of conventional imaging. Therapeutic decisions based on echo-planar MR imaging and conventional imaging results were compared. Diagnostic truth was determined by means of tissue diagnosis, further imaging findings, and follow-up findings (median, 18 months). RESULTS: Staging with total-body echo-planar MR imaging was correct in 18 patients (95%)--eight with metastases and 10 without--while staging with conventional imaging was correct in 15 patients (79%). In one patient, both echo-planar MR imaging and conventional imaging findings incorrectly indicated probable metastases. In one patient thought to have bone metastases at conventional imaging, echo-planar MR imaging findings were normal, which was correct. Two patients with stage IV disease were not suspected to have disease at conventional imaging: One had liver involvement and the other had skeletal metastases. The therapeutic decisions in these two patients were altered by the echo-planar MR imaging results. CONCLUSION: Total-body echo-planar MR imaging was at least as accurate as conventional imaging for staging newly diagnosed breast cancer and was faster, simpler, and completely noninvasive.

Adult↗
PubMed1999

Tobacco counseling practices of dentists compared to other health care providers in a midwestern region.

Tobacco counseling practices of dentists and other health care professionals in a predominantly rural region in the Upper Midwest were assessed to determine the need for professional education. A survey was mailed to all dentists, physicians, chiropractors, nurse practitioners, physician assistants, and public health nurses in a 16-county region. Half (51.9 percent) of providers returned usable surveys (n = 614). While dentists were more likely than physicians and other health professionals to accurately estimate their patients' tobacco use, they were less consistent than other professions in tobacco assessment and intervention, less supportive of tobacco intervention, less likely to report having strong tobacco cessation skill/knowledge levels, and more likely to perceive barriers to tobacco intervention. Three out of five dentists (61.1 percent) reported desire for further tobacco education. For dentists to effectively counsel patients regarding tobacco use, it is essential to integrate tobacco intervention education into dental school curricula and to offer continuing education regarding tobacco use intervention to practicing dentists. Recent state settlements with tobacco companies could provide funding for such education.

Adult↗