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Biomedical subjects

R C Johnson

Publications and source records attributed to R C Johnson.

At least 19 recordsLinked to original sources

Obstetric complications and anxiety during pregnancy: is there a relationship?

This review examines the contribution of recent research into the effects of anxiety during pregnancy. The focus of interest is upon the process of labor and delivery rather than its timing or the size of the baby. Therefore studies directed at areas of prematurity or low birthweight are specifically excluded as these have already been well evaluated in the literature. It is known that one proximal cause of obstetric complications is increased hormone levels in the uterus. It seems likely therefore that anxiety, a form of arousal, known to influence hormone levels, may be implicated as a distal determinant of obstetric complications. Attempts to evaluate this hypothesis have been hampered by methodological issues such as: poor definition and measurement of obstetric outcomes, in particular utilizing composite measures of diverse components; inappropriate measurements or over broad conceptualizations of anxiety; failure to account for confounding variables and inadequate sample sizes. On balance the evidence reviewed suggests that a general association between anxiety and obstetric complications per se does not exist, but specific types of anxiety, such as psychosocial stress, family functioning, or fear of childbirth may have associations with specific complications, such as prolonged labor or Cesarean section. Recent studies considering the effect of fear of childbirth, for example, on specific obstetric outcomes, such as type of delivery, have produced more clear-cut relationships. Recommendations for future research into the relationships between specific combinations of types of anxiety and individual obstetric complications are discussed.

Anxiety↗

Hydrology and the natural heritage of the Scottish mountains.

The physical natures of the Scottish mountains and their geographical position have created a montane environment, which can be considered as unique in European terms. The mountains of Scotland have been subjected to major environmental changes throughout the past centuries including climate change, deforestation, hydropower developments and more recently the expansion of plantation forestry. Mountain ecosystems have the ability to withstand large climatic variations and extreme events but it is suggested that they may not withstand some of the climatic barriers, which have recently been crossed. The greatest recent land use change in Scotland's mountains has been the expansion of plantation forests. The effects on headwater catchment hydrology are mainly in the reduction in runoff. It is suggested that plantation forestry has a more significant impact on the natural heritage through other influences such as water chemistry and river sediments. Future management of the Scottish mountains needs to consider the great natural heritage value in addition to other interests such as water resources, hydropower generation, commercial forestry and tourism.

Climate↗

Preclinical safety evaluation of recombinant human interleukin-10.

Escherichia coli-derived recombinant human interleukin-10 (rhuIL-10) has been evaluated in an extensive series of in vivo and in vitro nonclinical safety studies, including genetic toxicology, single- and repeat-dose systemic toxicity and toxicokinetics, reproductive toxicity, and specialized irritation studies. The primary test species in the toxicology studies were the mouse and monkey based on rhuIL-10 activity in receptor binding and ex vivo cytokine assays. Supported by a detailed preclinical program of therapeutic and prophylactic animal models in autoimmune diseases, the initial clinical development program has focused on investigating the therapeutic potential of rhuIL-10 (Tenovil) in Crohn's disease and rheumatoid arthritis. The results of the subcutaneous toxicity studies, up to 3 months dosing duration in mice and 6 months dosing duration in monkeys, support the development of rhuIL-10 for present and future clinical indications by the subcutaneous route of administration.

Animals↗

Host cell-specific expression of a p44 epitope by the human granulocytic ehrlichiosis agent.

The human granulocytic ehrlichiosis agent (HGEa) survives extreme differences between ticks and humans, possibly by use of differential expression of specific antigens for survival in different hosts. The role of the immunodominant p44 antigens is unknown. In this study, HGEa cultured in human or tick cells was probed with human, mouse, and hamster serum and with monoclonal antibodies (MAbs). p44 antigens were strongly expressed in human HL-60 cells but were strikingly reduced in tick cells. In HGEa alternately grown in HL-60 or tick cells, a p44 epitope recognized by MAb R5E4 was expressed in human but not tick cells. This was not a temperature effect, because incubation of infected tick cells at 37 degrees C did not induce expression of the p44 epitope. The p44 antigen predominates in human but not tick cells and may be involved in regulatory changes that mediate survival of the HGEa by immune modulation after tick transmission.

Animals↗

Distinct roles for the two Rho GDP/GTP exchange factor domains of kalirin in regulation of neurite growth and neuronal morphology.

The actin cytoskeleton, essential for neuronal development, is regulated in part by small GTP binding proteins of the Rho subfamily. Kalirin-9, with two Rho subfamily-specific GDP/GTP exchange factor (GEF) domains, localizes to neurites and growth cones of primary cortical neurons. Kalirin-9 overexpression in cultured cortical neurons induces longer neurites and altered neuronal morphology. Expression of the first GEF domain alone results in drastically shortened axons and excessive growth cones, mediated by Rac1. Expression of the second GEF domain alone induces axonal over-elongation and abundant filopodial neurites, mediated by RhoA. Coordination of the actions of the individual GEF domains through their presence in Kalirin-9, with its Sec14p, spectrin, and Src homology domain 3 motifs, is essential for regulating neurite extension and neuronal morphology.

3T3 Cells↗

How far do electrons move? A semiempirical investigation of thermal electron-transfer distances in cationic bis(hydrazine) and bis(hydrazyl) mixed-valence compounds.

A computational approach for estimating thermal electron-transfer reaction distances in symmetrical mixed-valence compounds is described and applied to a series of bis(hydrazine) and bis(hydrazyl) radical cations and derivatives, some of which have been investigated experimentally by Nelsen and co-workers. Ground-state semiempirical charge distributions are obtained by using optimized reactant geometries. Advantage is then taken of the approximate C(2) symmetry, or the approximate mirror symmetry, of each of the targeted compounds, and the inherent degeneracy of the corresponding electron-transfer reactions, such that the change in dipole moment (Delta-mu) upon charge transfer can be estimated from an appropriately distance-weighted sum of charge differences between approximately symmetry-equivalent atoms found on the donor and acceptor sides of the molecule. Delta-mu can then be related directly to the effective one-electron-transfer distance. We find that calculated adiabatic electron-transfer distances can differ appreciably from the geometric donor-site/acceptor-site separation distances. Furthermore, for a fixed geometric separation distance, the effective electron-transfer distance can vary considerably, depending on chemical substituent composition and/or isomeric configuration. Further advantage is taken of the approximate donor-site/acceptor-site symmetry, in the context of a Newton-Cave type analysis, to establish the relative importance of electronic delocalization effects versus self-polarization and inductive effects in diminishing or enhancing effective one-electron-transfer distances.

Journal Article↗

Expression of kalirin, a neuronal GDP/GTP exchange factor of the trio family, in the central nervous system of the adult rat.

Kalirin is a multifunctional protein identified by its interaction with peptidylglycine alpha-amidating monooxygenase, an enzyme essential for neuropeptide biosynthesis. Several forms of Kalirin exist, all containing spectrin-like repeats, a Dbl homology (DH) domain, and an adjacent pleckstrin homology (PH) domain; several different COOH-termini provide additional DH/PH domains and a putative protein kinase. Kalirin binds Rac1 and affects cytoskeletal organization, neuropeptide secretion, and iNOS activity. By in situ hybridization, the highest levels of Kalirin mRNA were found in the cerebral cortex, hippocampal formation, and Purkinje cells, with high levels also in thalamus, caudate putamen, septal nucleus, nucleus accumbens, amygdala, and anterior olfactory nucleus. Low levels of Kalirin mRNA were detected in the paraventricular, supraoptic, and reticular thalamic nuclei and in the ventromedial hypothalamic nucleus. Brain areas with high levels of Kalirin mRNA showed strong Kalirin-like immunoreactivity. Pyramidal neurons with strongly staining soma and long dendrites were observed primarily in layer 5 of the cerebral cortex. In the hippocampus, a uniform distribution of neurons with fine dendritic staining was observed in the pyramidal cell layer, in the granule cell layer, and in the hilar cells of the dentate gyrus as well as in isolated interneurons. Cerebellar Purkinje neurons exhibited intense staining in the soma and in extensive dendritic arbors extending to the surface of the molecular layer. During embryonic development, Trio, the Drosophila orthologue of Kalirin, plays an essential role in axon guidance; localization of Kalirin to the somatodendritic region of adult neurons provides the basis for future studies of regulation and function.

Animals↗

The neuronal Rho-GEF Kalirin-7 interacts with PDZ domain-containing proteins and regulates dendritic morphogenesis.

Spine function requires precise control of the actin cytoskeleton. Kalirin-7, a GDP/GTP exchange factor for Rac1, interacts with PDZ proteins such as PSD-95, colocalizing with PSD-95 at synapses of cultured hippocampal neurons. PSD-95 and Kalirin-7 interact in vivo and in heterologous expression systems. In primary cortical neurons, transfected Kalirin-7 is targeted to spines and increases the number and size of spine-like structures. A Kalirin-7 mutant unable to interact with PDZ proteins remains in the cell soma, inducing local formation of aberrant filopodial neurites. Kalirin-7 with an inactivated GEF domain reduces the number of spines below control levels. These results provide evidence that PDZ proteins target Kalirin-7 to the PSD, where it regulates dendritic morphogenesis through Rac1 signaling to the actin cytoskeleton.

Actins↗

Prediction of DISC substance abuse and dependency for ethnically diverse adolescents.

PURPOSE: This study examines the validity of selected items from the Substance Abuse Subtle Screening Inventory-Adolescent (SASSI-A) version in predicting Diagnostic Interview Schedule for Children (DISC version 2.3) Substance abuse and dependency (SA/D) for Native Hawaiian (i.e., indigenous people of the Hawaiian Islands) and non-Hawaiian adolescents (youth without any Native Hawaiian indigenous ancestry). METHODS: 542 students were randomly selected from the larger sample to participate in the DISC administration. Demographic information, SASSI-A scores, and DISC diagnoses were obtained for each student. Univariate and multiple logistic regressions were performed in the prediction of DISC SA/D. RESULTS: SASSI-A Factor 1, consisting of three items measuring substance use, was found to have the best utility, accounting for 18.1% of the variance, in predicting DISC SA/D. IMPLICATIONS: These results support selected SASSI-A items in screening for SA/D for Native Hawaiian and non-Hawaiian adolescents in Hawaii as compared to other community-based screening instruments for other populations.

Adolescent↗

Sociocultural factors influencing adolescent preference and use of native Hawaiian healers.

OBJECTIVE: Few studies have examined the use of alternative therapies among adolescents. This study examines the predictors of Native Hawaiian healer preference in the treatment of physical or emotional problems as well as the predictors of healer use. DESIGN: This study is a longitudinal cross-sectional design. SETTING: The survey was conducted in five high schools in Hawai'i. PARTICIPANTS: 1,322 high school students selected preference for and/or use of allopathic or alternative practitioners. MAIN OUTCOME MEASURES: Grade level, gender, ethnicity and cultural identity were used to predict healer preference. Healer preference, socioeconomic status and health status were used to predict healer use. RESULTS: Identification with the Hawaiian culture was the strongest predictor of healer preference for both Hawaiian and non-Hawaiian adolescents. Mental health was also predictive of healer preference for non-Hawaiians. Healer use by Native Hawaiian adolescents was also predicted by Hawaiian cultural identity. Gender, grade level, and socioeconomic variables were not predictive of healer preference or use. CONCLUSION: Cultural identity plays a significant role in the preference and use of alternative practitioners, especially for minority adolescent populations.

Adolescent↗

Control of transcription by nucleoid proteins.

Nucleoid proteins are a group of abundant DNA binding proteins that modulate the structure of the bacterial chromosome. They have been recruited as specific negative and positive regulators of gene transcription and their fluctuating patterns of expression are often exploited to impart an additional level of control with respect to environmental conditions.

Bacterial Proteins↗

Nuclear localization of the Saccharomyces cerevisiae HMG protein NHP6A occurs by a Ran-independent nonclassical pathway.

The Saccharomyces cerevisiae non-histone protein 6-A (NHP6A) is a member of the high-mobility group 1/2 protein family that bind and bend DNA of mixed sequence. NHP6A has only one high-mobility group 1/2 DNA binding domain and also requires a 16-amino-acid basic tail at its N-terminus for DNA binding. We show in this report that nuclear accumulation of NHP6A is strictly correlated with its DNA binding properties since only nonhistone protein 6 A-green fluorescent protein chimeras that were competent for DNA binding were localized to the nucleus. Despite the requirement for basic residues within the N-terminal segment for DNA binding and nuclear accumulation, this region does not appear to contain a nuclear localization signal. Moreover, NHP6A does not bind to the yeast nuclear localization signal receptor SRP1 and nuclear targeting of NHP6A does not require the function of the 14 different importins. Unlike histone H2B1 which contains a classical nuclear localization signal, entry of NHP6A into the nucleus was found to be independent of Ran as judged by coexpression of Ran GTPase mutants and was shown to occur at 0 degrees C after a 15-min induction. These unusual properties lead us to suggest that NHP6A entry into the nucleus proceeds by a nonclassical Ran-independent pathway.

Amino Acid Sequence↗

Equivalencies regarding the measurement and constructs of self-esteem and major life events in an Asian/Pacific islander sample.

Construct, scalar, and functional measurement equivalencies of the Rosenberg Self-Esteem Scale (RSES) and Major Life Events checklist (MLE) and the constructs assessed were investigated across groups differentiated on Hawaiian/part-Hawaiian and non-Hawaiian (e.g., Caucasian, Filipino, Hispanic, Japanese, and mixed/2 or more) ethnicity and gender. Initial results from maximum likelihood factoring with promax rotation showed that RSES negatively worded Item 5 loaded with the positively worded Items 1, 2, 4, 6, and 7 on 1 of 2 factors for Hawaiian/part-Hawaiian female participants. Similarly, negatively worded Item 8 and the same positively worded items comprised 1 of 2 factors for non-Hawaiian male participants. For the other 2 Ethnicity x Gender groups, factors were respectively comprised of the 5 positively and 5 negatively worded RSES items. Construct equivalence or simple (2-factor) structure underlying the RSES was indicated across the 4 groups after Items 5 and 8 were excluded from a subsequent factoring procedure. Simple structure showed that Factor 1 comprised the positively worded Items 1, 2, 4, 6, and 7, and the remaining negatively worded Items 3, 9, and 10 loaded on Factor 2. Scalar equivalence of the self-esteem and major life events measures was supported by the statistical nonsignificance of the Major Life Events x Ethnicity x Gender interaction effect in multiple regression models. The consistency in the absolute size and direction of the intercorrelations between overall self-esteem, self-esteem Factors 1 and 2, and major life events variables indicated the functional equivalence of respective measures and constructs assessed. Measurement equivalency findings concerning the RSES and MLE, the constructs measured, and their utility versus caution against their use in multiethnic studies were discussed.

Adolescent↗

Signaling mediated by the cytosolic domain of peptidylglycine alpha-amidating monooxygenase.

The luminal domains of membrane peptidylglycine alpha-amidating monooxygenase (PAM) are essential for peptide alpha-amidation, and the cytosolic domain (CD) is essential for trafficking. Overexpression of membrane PAM in corticotrope tumor cells reorganizes the actin cytoskeleton, shifts endogenous adrenocorticotropic hormone (ACTH) from mature granules localized at the tips of processes to the TGN region, and blocks regulated secretion. PAM-CD interactor proteins include a protein kinase that phosphorylates PAM (P-CIP2) and Kalirin, a Rho family GDP/GTP exchange factor. We engineered a PAM protein unable to interact with either P-CIP2 or Kalirin (PAM-1/K919R), along with PAM proteins able to interact with Kalirin but not with P-CIP2. AtT-20 cells expressing PAM-1/K919R produce fully active membrane enzyme but still exhibit regulated secretion, with ACTH-containing granules localized to process tips. Immunoelectron microscopy demonstrates accumulation of PAM and ACTH in tubular structures at the trans side of the Golgi in AtT-20 cells expressing PAM-1 but not in AtT-20 cells expressing PAM-1/K919R. The ability of PAM to interact with P-CIP2 is critical to its ability to block exit from the Golgi and affect regulated secretion. Consistent with this, mutation of its P-CIP2 phosphorylation site alters the ability of PAM to affect regulated secretion.

Adrenocorticotropic Hormone↗

Isolation of the etiologic agent of human granulocytic ehrlichiosis from the white-footed mouse (Peromyscus leucopus).

We examined white-footed mice (Peromyscus leucopus) from Minnesota for infection with the etiologic agent of human granulocytic ehrlichiosis (HGE). From April to September 1997, we collected P. leucopus from Washington County, Minnesota, an area enzootic for HGE. Blood was cultivated in HL60 cells for isolation of the HGE agent. Of 59 mice examined, only a single mouse was culture positive for the HGE agent. The 16S ribosomal DNA sequence of the isolate was determined to be identical to that of the HGE agent. The isolate was reactive with monoclonal antibodies to the 44-kDa antigen of the HGE agent and was infectious for laboratory mice.

Animals↗

Molecular typing of the etiologic agent of human granulocytic ehrlichiosis.

The p44 gene of the agent of human granulocytic ehrlichiosis (aoHGE) encodes a 44-kDa major outer surface protein. A technique was developed for the typing of the aoHGE based on the PCR amplification of the p44 gene followed by a multiple restriction digest with HindIII, EcoRV, and AspI to generate restriction fragment length polymorphism patterns. Twenty-four samples of the aoHGE were collected from geographically dispersed sites in the United States and included isolates from humans, equines, canines, small mammals, and ticks. Six granulocytic ehrlichiosis (GE) types were identified. The GE typing method is relatively simple to perform, is reproducible, and is able to differentiate among the various isolates of granulocytic ehrlichiae in the United States. These characteristics suggest that this GE typing method may be an important epizootiological and epidemiological tool.

Animals↗

Vitamin-mineral supplementation and accelerated chilling effects on quality of pork from pigs that are monomutant or noncarriers of the halothane gene.

We examined the effects of vitamin and mineral supplementation of the finishing diet on growth and accelerated chilling of carcasses on carcass and muscle traits of halothane gene carrier and noncarrier pigs. Barrows and gilts that were either monomutants (MON, n = 49) or noncarriers (NON, n = 28) of the halothane gene were fed a standard finishing diet until they reached 86 kg. They then were randomly assigned to one of four finishing diets formulated to contain 11 IU/kg vitamin E (0), 311 IU/kg vitamin E plus additional vitamins and minerals (300), 611 IU/kg vitamin E plus additional vitamins and minerals (600), or 911 IU/kg vitamin E plus additional vitamins and minerals (900) until they were slaughtered (118 kg). Alternating carcass sides were assigned either a normal chilling procedure (NC, 4 degrees C for 24 h) or an accelerated chilling procedure (AC, -20 degrees C for 1.5 h and then 4 degrees C for 22.5 h). Supplementing vitamin E in the finishing diet increased (P < 0.05) the concentration of vitamin E in the longissimus muscle. Supplementing vitamin E in the diets of MON pigs did not affect color, firmness, or cooking losses of loins or color and firmness of hams. For the NON genotype, increasing the level of vitamin E in the diet decreased (P < 0.05) the percentage of PSE loins and hams. Color and firmness scores of the gluteus medius and longissimus muscles were improved 0.4 unit (P < 0.005) by AC compared with NC of carcasses. Loin chop juiciness and flavor were improved (P < 0.05) in the MON genotype for AC compared to NC. Accelerated chilling reduced (P < 0.05) the percentage of PSE loins from 38 to 17% and PSE hams from 32 to 10% for the MON genotype, but percentage of PSE was not affected (P > 0.05) by chilling treatment for the NON genotype. No interaction between diet and chill treatments existed for muscle quality traits (P > 0.05). Supplementing finishing diets of NON pigs with at least 600 IU/kg vitamin E, in addition to other vitamins and minerals, or accelerated chilling of MON carcasses can reduce the incidence of PSE pork.

Animals↗

Stereotactic breast biopsy: a six-year surgical experience.

A retrospective review was done of all stereotactic breast biopsies performed at the Central Baptist Hospital Breast Center from February 1994 through December 1999. A total of 1,080 biopsies were performed in 1,026 patients, all by surgeons working independently. Masses were biopsied in 54% and calcifications in 40%. Eighteen percent of biopsies were malignant. The most common benign diagnosis was fibrocystic disease (72%), followed by fibroadenoma (19%), lymph node (2%), and papilloma (2%). The most common malignant diagnosis was invasive ductal carcinoma (40%) followed by ductal carcinoma in situ (32%) and mixed invasive and in situ ductal carcinoma (19%). A prebiopsy BI-RADS mammographic Category III was associated with a 2% incidence of malignancy; Category IV--17%; Category V--90%. Atypical ductal hyperplasia on stereotactic biopsy was upgraded to a malignant diagnosis after reexcision in 19% of the cases. The false-negative rate was 0.4% (sensitivity 99%) and the complication rate was 3%, mostly related to bleeding. Stereotactic biopsy is a safe and accurate technique for the minimally-invasive diagnosis of abnormal mammograms.

Adult↗