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Biomedical subjects

J Johnson

Publications and source records attributed to J Johnson.

At least 127 records · Page 7Linked to original sources

Locating a health advocate in a private obstetrics/gynecology office increases patient's receipt of preventive recommendations.

This study was performed to determine if adding a health advocate (HA) to the care team for postmenopausal women increased the number of women for whom the physician recommended screening tests or prevention strategies: cholesterol level, mammography, depression counseling, smoking cessation, or weight reduction. The study took place in two locations of a private obstetrician-gynecologist practice. In one location, an HA reviewed screening forms and counseled women about preventive services recommended by the physician. In the second location, women completed the screening form, but treatment occurred as usual. Women were eligible if they were postmenopausal or age 50 or over and were being seen for preventive care. A total of 210 postmenopausal women were screened. Women who were screened when the HA was present (n = 85) did not differ from women screened at the intervention location when the HA was not present (n = 68) or screened at a second practice location (n = 57) in the prevalence of risk factors. Women were significantly more likely to receive indicated preventive recommendations when the HA was present (24% versus 73%, p < 0.001). For breast cancer screening, nearly all women screened when the HA was present received a referral compared to about one third of women screened when the HA was not present (OR = 3.0, 95% CI 1.8-5.2). Women are more likely to receive recommendations based on screening data when ancillary staff are available to assist in patient education and referral and to encourage physician recommendations. Further work is needed to identify cost-effective methods for supporting physicians' preventive care efforts.

Cholesterol↗

Intravenous administration of stabilized antisense lipid particles (SALP) leads to activation and expansion of liver natural killer cells.

Stabilized antisense lipid particles (SALP) have been developed for the systemic delivery of oligonucleotides. The impact of intravenous SALP administration was measured with respect to activation of natural killer (NK) and NK1.1+ T (NKT) cells in the livers of immunocompetent mice. Treatment with a SALP containing a highly mitogenic oligonucleotide (INX-6295) generated an increase in NK cytolytic activity and cell number within the liver but did not appear to affect the number of hepatic NKT cells or their cytolytic activity. The same results were observed after intravenous administration of the mitogenic oligonucleotide alone. Interestingly, treatment with a SALP containing a weakly mitogenic oligonucleotide (INX-6300) also activated the liver NK cells, whereas the oligonucleotide alone was unable to elicit these effects. The NK stimulatory activity of a SALP containing INX-6300 required both lipid and oligonucleotide components. These results demonstrate that in addition to modifying the pharmacokinetics and biodistribution of intravenously administered oligonucleotides, SALP possess immunostimulatory activity independent of oligonucleotide mitogenicity, which can serve as an adjuvant to antisense therapies for cancer.

Adjuvants, Immunologic↗

Phylogenetic relationships of agaric fungi based on nuclear large subunit ribosomal DNA sequences.

Phylogenetic relationships of mushrooms and their relatives within the order Agaricales were addressed by using nuclear large subunit ribosomal DNA sequences. Approximately 900 bases of the 5' end of the nucleus-encoded large subunit RNA gene were sequenced for 154 selected taxa representing most families within the Agaricales. Several phylogenetic methods were used, including weighted and equally weighted parsimony (MP), maximum likelihood (ML), and distance methods (NJ). The starting tree for branch swapping in the ML analyses was the tree with the highest ML score among previously produced MP and NJ trees. A high degree of consensus was observed between phylogenetic estimates obtained through MP and ML. NJ trees differed according to the distance model that was used; however, all NJ trees still supported most of the same terminal groupings as the MP and ML trees did. NJ trees were always significantly suboptimal when evaluated against the best MP and ML trees, by both parsimony and likelihood tests. Our analyses suggest that weighted MP and ML provide the best estimates of Agaricales phylogeny. Similar support was observed between bootstrapping and jackknifing methods for evaluation of tree robustness. Phylogenetic analyses revealed many groups of agaricoid fungi that are supported by moderate to high bootstrap or jackknife values or are consistent with morphology-based classification schemes. Analyses also support separate placement of the boletes and russules, which are basal to the main core group of gilled mushrooms (the Agaricineae of Singer). Examples of monophyletic groups include the families Amanitaceae, Coprinaceae (excluding Coprinus comatus and subfamily Panaeolideae), Agaricaceae (excluding the Cystodermateae), and Strophariaceae pro parte (Stropharia, Pholiota, and Hypholoma); the mycorrhizal species of Tricholoma (including Leucopaxillus, also mycorrhizal); Mycena and Resinomycena; Termitomyces, Podabrella, and Lyophyllum; and Pleurotus with Hohenbuehelia. Several groups revealed by these data to be nonmonophyletic include the families Tricholomataceae, Cortinariaceae, and Hygrophoraceae and the genera Clitocybe, Omphalina, and Marasmius. This study provides a framework for future systematics studies in the Agaricales and suggestions for analyzing large molecular data sets.

Agaricales↗

An overview of psychosocial support services. Resources for healing.

Cancer has the potential of threatening all of a person's resources: physical, psychological, social, spiritual, and economic. It is as if the experience of cancer takes on a life cycle of its own that starts with the shock of diagnosis and continues well beyond the completion of treatment. Psychosocial support services of various types need to be made available throughout the cancer experience. Participation in these services affords people the opportunity to learn positive coping skills, to recognize that they are not alone, to discover how to enjoy living in the present, and to attach a different meaning to the words "hope" and "healing." Restoring a sense of wholeness to one's mind, body, and spirit is equally as important as receiving the most effective therapy for the cancer.

Humans↗

Sensorineural and conductive hearing loss associated with lateral semicircular canal malformation.

OBJECTIVE: Lateral semicircular canal (LSCC) malformation is one of the most common radiological inner ear malformations. Traditionally, inner ear malformations are thought to be associated with sensorineural hearing loss (SNHL). Recent experience with patients with LSCC malformation suggested that LSCC malformation may be associated with both SNHL and conductive hearing loss (CHL). The auditory phenotype associated with LSCC malformation is not well delineated. The objective of this study is to define the nature of the hearing loss associated with LSCC malformation. STUDY DESIGN: Retrospective review METHODS: Retrospective review of clinical records, audiological evaluation, and imaging studies. RESULTS: Two patients with unilateral and 13 patients with bilateral LSCC malformation were identified. LSCC malformation was associated with CHL in 14% (4 ears), SNHL in 71% (20 ears), normal hearing in 11% (3 ears) and CHL due to atresia in one ear. Hearing loss varied from mild to profound but did not correlate with the severity of LSCC malformation. In bilateral malformation, the hearing loss was asymmetric in half of the cases. Malformation of the posterior limb of the LSCC was always associated with a large vestibular aqueduct. An absent or rudimentary LSCC was invariably associated with a cochlear abnormality. CONCLUSIONS: LSCC malformation, like other inner ear malformations such as large vestibular aqueduct and X-linked mixed deafness with perilymph gusher, can be associated with CHL, SNHL, or normal hearing. Children with unexplained conductive hearing loss often undergo exploratory surgery to improve hearing. Given that inner ear malformations may be associated with a pure CHL, it is critical that children undergo computed tomography scan of the temporal bone prior to undergoing exploratory surgery.

Adolescent↗

Methionine oxidation within the cerebroside-sulfate activator protein (CSAct or Saposin B).

The cerebroside-sulfate activator protein (CSAct or Saposin B) is a small water-soluble glycoprotein that plays an essential role in the metabolism of certain glycosphingolipids, especially sulfatide. Deficiency of CSAct in humans leads to sulfatide accumulation and neurodegenerative disease. CSAct activity can be measured in vitro by assay of its ability to activate sulfatide-sulfate hydrolysis by arylsulfatase A. CSAct has seven methionine residues and a mass of 8,845 Da when deglycosylated. Mildly oxidized, deglycosylated CSAct (+16 Da), separated from nonoxidized CSAct by reversed-phase high-performance liquid chromatography (RP-HPLC), showed significant modulation of the in vitro activity. Because oxidation partially protected against CNBr cleavage and could largely be reversed by treatment with dithiothreitol, it was concluded that the major modification was conversion of a single methionine to its sulfoxide. High-resolution RP-HPLC separated mildly oxidized CSAct into seven or more different components with shorter retention times than nonoxidized CSAct. Mass spectrometry showed these components to have identical mass (+16 Da). The shorter retention times are consistent with increased polarity accompanying oxidation of surface-exposed methionyl side chains, in general accordance with the existing molecular model. A mass-spectrometric CNBr mapping protocol allowed identification of five of the seven possible methionine-sulfoxide CSAct oxoforms. The most dramatic suppression of activity occurred upon oxidation of Met61 (26% of control) with other residues in the Q60MMMHMQ66 motif falling in the 30-50% activity range. Under conditions of oxidative stress, accumulation of minimally oxidized CSAct protein in vivo could perturb metabolism of sulfatide and other glycosphingolipids. This, in turn, could contribute to the onset and progression of neurodegenerative disease, especially in situations where the catabolism of these materials is marginal.

Amino Acid Sequence↗

Inhibition of CDKs as a therapeutic modality.

Altered cell cycle control has emerged as a recurring theme in neoplasia. Strategies that would return toward normal the altered cell cycle control present in tumor cells have appeal as novel approaches to cancer treatment. Cyclin-dependent kinases (CDKs) control the progression through the cell cycle, operating at the transition from the G2 to M and G1 to S phases, and progression through S. CDKs are regulated by a complex set of mechanisms, including the presence of activating cyclins, regulatory phosphorylations, and endogenous CDK inhibitors at "checkpoints." This overview focuses on progress in defining compounds that can antagonize directly the action of CDKs. These have emerged as various types of ATP site-directed inhibitors, including flavopiridol, N-substituted adenine derivatives, the natural product butyrolactone, staurosporine derivatives, and, more recently, the synthetic paullones. Paullones appear to be of interest in that one of the most active members of the class, 9-nitropaullone (alsterpaullone), requires relatively brief periods of exposure to living cells in order to effect lasting effects on cellular and proliferative potential. Two of these compounds, flavopiridol and UCN-01 (7-hydroxy-staurosporine), have entered early clinical trials and achieved concentrations that might potentially modulate CDK function. In the case of UCN-01, unexpected human plasma protein binding might prevent direct inhibition of CDKs but allow drug concentrations to be achieved that indirectly affect CDKs by checkpoint abrogation. Further studies with CDK inhibitors should define the expected end point of CDK inhibition more clearly in preclinical models and clinical systems, including cytostasis, apoptosis, or differentiation.

Antineoplastic Agents↗

Relation of familial schizophrenia to negative symptoms but not to the deficit syndrome.

OBJECTIVE: Although a family history of schizophrenia has been associated with negative symptoms, family history is inconsistently related to the presence of the deficit syndrome. METHOD: The authors assessed family history and the deficit syndrome in 99 patients with DSM-III-R-diagnosed schizophrenia who were assessed during clinical treatment. Of these 99 patients, 45 were assessed both while antipsychotic free and during antipsychotic treatment to index their treatment response. RESULTS: Patients with (N=39) and without (N=60) a family history of schizophrenia had similar proportions of the deficit syndrome. Yet family history and deficit syndrome categorizations identified a group with greater negative symptoms on the Positive and Negative Syndrome Scale. Those with a family history had greater emotional withdrawal, poor rapport, and lack of spontaneity. Groups with and without the deficit syndrome similarly differed in these symptoms but also in affective blunting, motor retardation, and passive or apathetic social withdrawal. The study involving antipsychotic-free and antipsychotic treatment phases showed main medication effects explaining positive, psychopathology, depression, and activation symptoms but not negative symptoms. Only patients without a family history had improved negative symptoms with antipsychotic treatment. CONCLUSIONS: Patients with a family history of schizophrenia had greater and more treatment-resistant negative symptoms than those without a family history. They were not more likely to have the deficit syndrome. The group with a family history had more pathology only in negative symptoms related to psychosocial function. The stable negative symptoms specifically related to the genetic vulnerability to inherit schizophrenia might be those associated with psychosocial functioning.

Adaptation, Psychological↗

Respiratory bronchiolitis associated with severe dyspnea, exertional hypoxemia, and clubbing.

Respiratory bronchiolitis-associated interstitial lung disease (RBILD) is a distinct clinicopathologic disease described almost exclusively in cigarette smokers.(1) (2) The disease usually presents with mild symptoms and is associated with a good prognosis. (2) Severe lung dysfunction has not been reported with RBILD, which is often confused clinically and radiographically with desquamative interstitial lung disease or idiopathic pulmonary fibrosis (IPF). Two patients with RBILD who developed severe dyspnea, hypoxemia, and clubbing are described. Initially, IPF was diagnosed in both patients. The severity of symptoms was such that the first patient's room air saturation was 85% and the second patient had severe impairment of lung function, with FEV(1) of 39% and FVC of 40%. Advanced lung disease required supplemental home oxygen therapy in the first patient and referral for lung transplant evaluation in the second patient. After a detailed review of histology revealed a diagnosis of RBILD, both patients were encouraged to stop smoking; smoking cessation led to considerable improvement in symptoms and lung function tests. We conclude that advanced lung dysfunction occurs in some patients with RBILD and should not dissuade that diagnosis.

Adult↗

Cloning and molecular characterization of a gene encoding a Cryptosporidium parvum putative 20S proteasome beta1-type subunit.

A DNA sequence composed of 1281 nucleotides (nt) consisting of a single open reading frame (ORF) encoding a putative 20S proteasome beta1-type subunit was isolated from clones derived from genomic libraries constructed from the KSU-1 isolate of Cryptosporidium parvum. Southern blot analysis suggested that the sequenced DNA exists in the C. parvum genome as a single copy; transcription was verified through reverse transcription-polymerase chain reaction (RT-PCR) performed on total RNA isolated from C. parvum sporozoites. The predicted protein consists of 210 amino acids (aa), contains characteristic amino acids common to all proteasomal subunits, and shares stronger similarity to the beta1-type subunit of yeast than to other types of beta-subunits.

Adenosine Triphosphatases↗

The infant rat learns about alcohol through interaction with an intoxicated mother.

BACKGROUND: Infant rats detect the presence of alcohol in milk when the dam suffers a moderate state of alcohol intoxication. The present study examined when rat pups begin to show behavioral changes indicative of the interaction with an intoxicated dam. The study also attempted to determine if infantile experiences involving a moderately intoxicated dam result in alcohol-derived memories with a particular hedonic content. METHODS: Infant rats were allowed to interact during postnatal days (PDs) 3, 5, 7, 9, 11 and 13 with alcohol-intoxicated (EtOH dose: 2.5 g/kg) or alcohol-free dams. After the interaction took place, some pups were tested in terms of ultrasonic vocalizations (USVs) and motor reactivity when isolated and placed on each of two distinctive tactile surfaces (sandpaper or soft fabric) presented in a counterbalanced order, and the second of which was always paired with ambient ethanol odor. At PD 14 pups were evaluated in terms of the preference for texture (sandpaper versus soft fabric) and odor (alcohol versus clove) as well as alcohol ingestion. RESULTS: Very early in life (PD 3) USVs and overall activity were significantly higher in pups that had previously interacted with an intoxicated dam than in those exposed to an alcohol-free dam. Although this difference was not apparent during the following days, it was clear that a specific memory of alcohol's chemosensory cues was formed. Pups interacting with intoxicated dams followed by pairing of ethanol odor and an arousing texture (sandpaper), later avoided this texture in the preference test; pups that interacted with alcohol-free dams did not show this effect. The former animals also exhibited less consumption of alcohol than preweanlings never exposed to alcohol in the context of nursing. CONCLUSIONS: In conjunction with prior studies these results indicate that very early in ontogeny the infant processes the presence of ethanol, and perhaps its effect on its mother, within the nursing context. Under the present experimental circumstances infants appear to acquire alcohol-related information that comprises an aversive hedonic component.

Alcoholic Intoxication↗

A computer generated induction system for hospitalized patients starting on oral anticoagulant therapy.

There is an increasing use of computer-based dosage programs to monitor oral anticoagulant therapy in outpatients. DAWN AC INDUCTION by 4S, UK, is a computer generated system to initiate oral anticoagulant therapy providing fast access to the maintenance program. This method of initiation of anticoagulant therapy has not been validated. We therefore randomized 50 hospitalized patients starting oral anticoagulation to control by the computer and 51 by manual dosing using a dosing schedule based on a locally defined algorithm. After a 7 days follow up, the daily mean INR was 2.09 and 2.07 and the proportion of dose adjustments was 48% and 45% in the computer and manually controlled groups respectively. Twenty-eight % of the patients monitored by the computer system required at least one manual overriding. DAWN AC INDUCTION provided a simple and accurate organization of the data, with an overall quality comparable to that of the manual system. Furthermore, the induction programme provided simple access to the maintenance programme. Although it required careful monitoring, the programme resulted in a significant saving in personnel time.

Administration, Oral↗

Iliac crest autogenous bone grafting: donor site complications.

Autogenous bone grafting is often done in orthopaedic surgery for a variety of conditions. The iliac crest is currently the most common donor site for obtaining autogenous bone graft. We searched the literature to summarize reported complications related to the donation of autogenous bone from the iliac crest. Our review revealed reports of arterial injury, ureteral injury, herniation, chronic pain, nerve injury, infection, fracture, pelvic instability, cosmetic defects, hematoma, and tumor transplantation. Currently, autogenous bone grafting is a necessary part of the treatment of various orthopaedic conditions. Obtaining bone from the iliac crest can be associated with significant morbidity. As bone grafting technology emerges, the known complications of the current standard should be weighed against the risk of alternate therapies.

Bone Transplantation↗

Pulmonary veno-occlusive disease: a case series and new observations.

STUDY OBJECTIVES: The aim of this study was to describe our experience at one institution with pulmonary veno-occlusive disease (PVOD) during the past 10 years, with particular reference to new findings and long-term outcome. SETTING: Tertiary care, academic medical center. PATIENTS AND METHODS: Eleven patients who were evaluated and treated for PVOD at our institution were retrospectively studied. Included were all available clinical, radiographic, hemodynamic, and pathologic data. RESULTS: All 11 patients in our series had at least one symptom or clinical finding that, in conjunction with known pulmonary hypertension, suggested the diagnosis of PVOD. Digital clubbing, not previously reported in PVOD, was found in 5 patients, rales in 6, and increased interstitial markings on chest radiograph in 10. Half of the 10 patients who underwent acute vasodilator testing exhibited a decrease in pulmonary artery pressure of > 20%, although one patient died shortly after receiving IV calcium-channel blockers. Three patients have demonstrated sustained clinical improvement with therapy, which includes calcium-channel blockers, epoprostenol, and lung transplantation in one patient each. However, outcome was generally poor, with a 72% mortality within 1 year of diagnosis. CONCLUSION: The diagnosis of PVOD requires a high clinical suspicion. However, both physical examination findings and radiographic studies often provide clues to the diagnosis, which may obviate the need for lung biopsy in the majority of cases. Although there may be patients who respond to medical therapy, the use of vasoactive medications in patients with PVOD should be undertaken with great caution. Long-term survival is poor, and lung transplantation remains the only proven therapy.

Adult↗