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Biomedical subjects

K Nelson

Publications and source records attributed to K Nelson.

At least 37 records · Page 2Linked to original sources
PubMed1996

Neuronatin mRNA in PC12 cells: downregulation by nerve growth factor.

Neuronatin was recently cloned from neonatal rat brain (Biochem, Biophys. Res. Commun., 201 (1994) 1227-1234). In subsequent studies, we noted neuronatin mRNA was brain-specific and that there were two alternatively spliced forms, alpha and beta (Brain Res., 690 (1995) 92-98). Furthermore, on sequencing the human neuronatin gene, it was determined that the alpha-form was encoded by three exons, and the beta-form was encoded by the first and third exons only (Genomics, 33 (1996) 292-297). The middle exon was spliced out in the beta-form. The human neuronatin gene is located in single copy of chromosome 20q 11.2-12 (Brain Res., 723 (1996) 8-22). These studies called for an understanding of the function of this gene. Therefore, we studied the expression of neuronatin in PC12 cells, an established model of neuronal growth and differentiation. Neuronatin mRNA expression was found to be abundant in undifferentiated PC12 cells. Treatment with nerve growth factor (NGF), resulting in neuronal differentiation, was associated with a downregulation of neuronatin mRNA expression. Removal of NGF was associated with a return of neuronatin mRNA levels towards baseline. These effects appear to be specific for NGF as they were not seen with transforming growth factor, epidermal growth factor, 12-O-tetradecanoylphorbol-13-acetate or dexamethasone. Although, basic fibroblast growth factor also reduced neuronatin mRNA levels, the effect was less pronounced than with NGF. The NGF-induced decreased in neuronatin mRNA occurred even in the presence of protein and RNA syntheses inhibitors. Of the two spliced forms, only the alpha-form was expressed in PC12 cells. In conclusion, we report the presence of neuronatin mRNA in PC12 cells, and that NGF downregulates its expressions. These findings provide a basis for investigating the role of neuronatin in neuronal growth and differentiation.

Aging↗
PubMed1996

Regulation of cornifin alpha expression in the vaginal and uterine epithelium by estrogen and retinoic acid.

In this study, we analyze the regulation of the squamous-specific gene, cornifin alpha, by estrogen and retinoic acid in vaginal and uterine epithelial cells. In ovariectomized animals, the vaginal epithelium consists of a stratified, nonkeratinizing epithelium which changes into a highly-stratified, keratinizing epithelium upon treatment with estradiol. This transition is accompanied by a dramatic induction of the crosslinked envelope precursor, cornifin alpha. An increase in cornifin mRNA can be detected as early as 3 h after treatment. A similar effect is observed for the synthetic estrogenic agent diethylstilbestrol while other steroid hormones, including testosterone, progesterone or dexamethasone have little effect on cornifin expression. In contrast to the vagina, estradiol induces neither squamous differentiation nor expression of cornifin alpha in the uterine epithelium. Similar to the action of estradiol, vitamin A-deficiency greatly enhances squamous differentiation and keratinization in the vaginal epithelium. But unlike estradiol, it induces squamous metaplasia in the normally columnar, uterine epithelium, which eventually is replaced by a keratinizing epithelium in severe deficiency. This transition is associated with an induction of cornifin alpha expression. Immunohistochemical and in situ hybridization analysis localizes cornifin protein and mRNA in the suprabasal layers of the squamous epithelium. Our results demonstrate that estrogen and retinoids play key roles in the regulation of differentiation and cornifin alpha expression in the uterine and vaginal epithelium.

Animals↗
PubMed1996

Evaluation of an otitis media with effusion screening pilot programme.

AIM: To evaluate an otitis media with effusion (OME) pilot screening programme carried out in a low socioeconomic status population. METHODS: The evaluation methodology involved a literature review, key informant interviews and evaluation of the programme according to standard screening criteria. Operational analysis was carried out in which inputs, outputs and costs were analysed. RESULTS: 731 children were screened. The proportion of the target population screened was 91.2%. Forty nine point seven percent (363) of children tested had bilateral OME on at least one occasion, of whom 25.3% (92) were referred to otorhinolaryngology (ORL). The average cost of screening each child was $46.10, of detecting a case of bilateral OME $92.85, and of detecting a case requiring referral $117.03. CONCLUSIONS: The programme demonstrated that a low socioeconomic status population can be successfully screened; that the high rate of spontaneous resolution of OME should be taken into account when designing screening protocols; that screening has significant impact on secondary services; and, screening is likely to have other benefits arising from more frequent contact with children and parents. The operational success of the pilot gives no indication, however, concerning the long term outcomes of tympanometry screening. The authors conclude that further research is required to establish the long term benefits of OME screening, and resource requirements.

Child, Preschool↗
PubMed1996

Effect of clonidine and yohimbine on sleep in healthy men: a double-blind, randomized, controlled trial.

OBJECTIVE: To study the acute effect of clonidine, an alpha 2-adrenoceptor agonist, and yohimbine, an alpha 2-adrenoceptor antagonist, on nocturnal sleep in healthy men. SETTING: McGuire Veteran Affairs Medical Center, Richmond, Virginia, USA. SUBJECTS: Eight healthy male volunteers. METHODS: Each subject slept in the sleep laboratory for 2 consecutive nights on three separate sessions, at 3-week intervals. On the 2nd night of each session, the subjects received yohimbine (5.4 mg), clonidine (0.1 mg), or placebo in a double-blind, randomized, placebo-controlled, crossover design. RESULTS: There were no apparent effects of yohimbine. In contrast, clonidine completely suppressed rapid eye movement (REM) sleep in one subject and reduced REM sleep in the remaining seven subjects. CONCLUSION: Our study confirms that clonidine markedly decreases REM, even at a low single dose, and supports the hypothesis of the important role of alpha 2-receptors in controlling REM sleep.

Adrenergic alpha-Agonists↗
PubMed1996

Increasing influenza immunization among high-risk patients: education or financial incentive?

PURPOSE: To determine whether an educational brochure or a lottery-type incentive increases influenza immunization rates. PATIENTS AND METHODS: In a prospective, single-blind factorial design randomized trial at an urban community health center, all high-risk patients (n = 797) seen in the preceding 18 months were randomly assigned to one of four groups: a control group; a group mailed a large print, illustrated educational brochure emphasizing factors important to patients in making a decision about influenza immunization; a group mailed a lottery-type incentive announcing that all patients receiving influenza immunization would be eligible for grocery gift certificates; and a group mailed both educational brochure and incentive. Immunization was free, available without an appointment, and recorded by a computerized tracking system. RESULTS: The group mailed the brochure was more likely to be immunized than control (odds ratio [OR] = 2.29, 95% confidence interval [CI] 1.45 to 3.61), as was the group mailed the incentive (OR = 1.68, 95% CI 1.05 to 2.68), but there was no difference between the group mailed both interventions and the control group. The effectiveness of the brochure was more striking for individuals who had not accepted immunization in the prior year (OR = 4.21, 95% CI 2.48 to 7.14), suggesting a true educational effect rather than simply a reminder. CONCLUSION: In this community health center setting, an illustrated educational brochure increased influenza immunization among high-risk patients, a lottery-type incentive was much less effective, and both together was not effective.

Aged↗
PubMed1996

The effect of music amplitude on the reaction to unexpected visual events.

The effects of music amplitude on participants' response time to randomly presented, unexpected, visual events were investigated. Ninety participants completed a motor-reaction task without music and with music played at 60, 70, or 80 dBA. Males preferred more intense music than females did, with males selecting a comfort level of 72 dBA and females, 66 dBA. However, participants' reaction time and the total time to respond to a randomly activated red light were independent of gender. All participants responded more quickly when the music was played at 70 dBA (close to their comfort level) than when it played at lower (60 dBA) or higher (80 dBA) amplitudes. It is proposed that people may react more quickly to visual events (e.g., the sudden appearance of a plane on the screen of an air traffic controller, or the unpredictable activation of a car's rear brake lights when driving) with music playing at a volume preset to maintain individual comfort levels against other situational background noise.

Adolescent↗
PubMed1996

Occipital arteriovenous malformations: visual disturbances and presentation.

BACKGROUND: Occipital arteriovenous malformations (AVMs) cause a variety of visual disturbances and headaches. Early diagnosis may lead to treatment that reduces the risk of hemorrhages, visual field loss and other neurologic deficits, and death. METHODS: We reviewed the records of the 70 patients with occipital AVMs referred to New York University Medical Center to investigate the mode of presentation and the outcome of treatment. RESULTS: Sixty-eight patients presented with one or more symptoms, including homonymous visual disturbances in 39, headache in 39, seizures in 20, and hemorrhage in twenty-six. Visual field loss was more common (p = 0.0007) and more severe (p = 0.0002) in patients who bled than in those with unruptured AVMs (16/44). The frequency of visual field loss was not associated with calcarine artery supply to the AVM. Prior to treatment, the fields improved in five patients with visual loss associated with a hemorrhage. Forty-six patients were treated with embolization, surgery, radiosurgery, or a combination of therapies. The AVM was eliminated in 19 of 20 patients (nine with preoperative partial embolization) treated with surgery versus in 4 of 27 patients treated only with embolization. There were two AVM-associated deaths, two subarachnoid hemorrhages, and four new neurologic deficits after treatment. Visual fields were worse in 15 patients, unchanged in 22, and improved in eight. CONCLUSIONS: Whereas some features of headache and visual symptoms are similar for occipital AVMs and migraine, the two disorders are usually distinguishable. Visual field improvement can spontaneously occur in patients who have had loss secondary to an intracerebral bleed. Treatment with embolization or surgery, particularly with surgical excision of the AVM, can result in new or worse visual field loss.

Adolescent↗
PubMed1996

Publication-quality labeling of gels using transparency-mounted photographs and word processing software.

Obtaining a high quality nucleic acid or protein gel may be an easier and less daunting task than labeling the gel for publication. Techniques for adding information and identifiers to gels range from laboriously applying lettering or labels on gel photographs to computerized approaches that work directly with digitized gel images and produce photographic-quality output. The computerized approach may require specialized software and a considerable investment in a photographic-quality output device, like a dye sublimation printer. It can be argued that electronically processed gel images do not actually achieve the quality readily obtained photographically. We describe an approach that uses photographic gel images that are quickly and easily labeled using the drawing-lettering capability of a commercial word processor in widespread use (Microsoft Word for Windows Version 6).

Audiovisual Aids↗
PubMed1995

14-3-3 proteins: potential roles in vesicular transport and Ras signaling in Saccharomyces cerevisiae.

Deletion of the clathrin heavy-chain gene, CHC1, in the budding yeast Saccharomyces cerevisiae results in growth, morphological, and membrane trafficking defects, and in some strains chc1-delta is lethal. A previous study identified five genes which, in multicopy, rescue inviable strains of Chc- yeast. Now we report that one of the suppressor loci, BMH2/SCD3, encodes a protein of the 14-3-3 family. The 14-3-3 proteins are abundant acidic proteins of approximately 30 kDa with numerous isoforms and a diverse array of reported functions. The Bmh2 protein is > 70% identical to the mammalian epsilon-isoform and > 90% identical to a previously reported yeast 14-3-3 protein encoded by BMH1. Single deletions of BMH1 or BMH2 have no discernable phenotypes, but deletion of both BMH1 and BMH2 is lethal. High-copy BMH1 also rescues inviable strains of Chc- yeast, although not as well as BMH2. In addition, the slow growth of viable strains of Chc- yeast is further impaired when combined with single bmh mutations, often resulting in lethality. Overexpression of BMH genes also partially suppresses the temperature sensitivity of the cdc25-1 mutant, and high-copy TPK1, encoding a cAMP-dependent protein kinase, restores Bmh- yeast to viability. High-copy TPK1 did not rescue Chc- yeast. These genetic interactions suggest that budding-yeast 14-3-3 proteins are multifunctional and may play a role in both vesicular transport and Ras signaling pathways.

14-3-3 Proteins↗
PubMed1995

Relationship between evolutionary rate and cellular location among the Inv/Spa invasion proteins of Salmonella enterica.

For 21 strains of Salmonella enterica, nucleotide sequences were obtained for three invasion genes, spaO, spaP, and spaQ, of the chromosomal inv/spa complex, the products of which form a protein export system required for entry of the bacteria into nonphagocytic host cells. These genes are present in all eight subspecies of the salmonellae, and homologues occur in a variety of other bacteria, including the enteric pathogens Shigella and Yersinia, in which they are plasmid borne. Evolutionary diversification of the invasion genes among the subspecies of S. enterica has been generally similar in pattern and average rate to that of housekeeping genes. However, the range of variation in evolutionary rate among the invasion genes is unusually large, and there is a relationship between the evolutionary rate and cellular location of the invasion proteins, possibly reflecting diversifying selection on exported proteins in adaptation to variable host factors in extracellular environments. The SpaO protein, which is hypervariable in S. enterica and exhibits only 24% sequence identity with its homologues in Shigella and Yersinia, is secreted. In contrast, the membrane-associated proteins SpaP, SpaQ, and InvA are weakly polymorphic and have > 60% sequence identity with the corresponding proteins of other enteric bacteria. Acquisition of the inv/spa genes may have been a key event in the evolution of the salmonellae as pathogens, following which the invention of flagellar phase shifting facilitated niche expansion to include warm-blooded vertebrates.

Adhesins, Bacterial↗
PubMed1995

Leukocyte CD18 receptors may be a better target than ICAM-1 ligands for reducing histologic evidence of cellular and vascular rejection in the rabbit.

Building evidence suggests that blocking the ICAM-1/CD18 interaction may affect the course of graft rejection. Treatment with monoclonal antibody (mAb) to CD18 was compared to antibody to ICAM-1 in a rabbit heterotopic heart transplant model to determine whether blocking the leukocyte receptor for ICAM-1, CD18, was more effective than antibody targeting of the ligand for ICAM-1. Following transplantation, 28 recipient rabbits were randomized to receive either placebo, mAb to CD18, or mAb to ICAM-1 for 7 days until sacrifice. The cellular rejection grade and percentage of arteries with vascular rejection were significantly lower in animals treated with anti-CD18 than with anti-ICAM-1. As assessed by histology, antibody treatment was more effective in reducing both cellular and vascular rejection when directed at the leukocyte receptor CD18 than the ICAM-1 ligand. These findings suggest that other ICAM ligands may play an active role in the immune response and that CD18 may be important for migration of lymphocytes through myocardium.

Animals↗
PubMed1995

Is the richness of our visual world an illusion? Transsaccadic memory for complex scenes.

Our construction of a stable visual world, despite the presence of saccades, is discussed. A computer-graphics method was used to explore transsaccadic memory for complex images. Images of real-life scenes were presented under four conditions: they stayed still or moved in an unpredictable direction (forcing an eye movement), while simultaneously changing or staying the same. Changes were the appearance, disappearance, or rotation of an object in the scene. Subjects detected the changes easily when the image did not move but when it moved their performance fell to chance. A grey-out period was introduced to mimic that which occurs during a saccade. This also reduced performance but not to chance levels. These results reveal the poverty of transsaccadic memory for real-life complex scenes. They are discussed with respect to Dennett's view that much less information is available in vision than our subjective impression leads us to believe. Our stable visual world may be constructed out of a brief retinal image and a very sketchy, higher-level representation along with a pop-out mechanism to redirect attention. The richness of our visual world is, to this extent, an illusion.

Eidetic Imagery↗
PubMed1995

Bacterial vaginosis and HIV seroprevalence among female commercial sex workers in Chiang Mai, Thailand.

OBJECTIVE: To investigate the relationship between HIV seropositivity and bacterial vaginosis (BV) in a population at high risk for sexual acquisition of HIV. DESIGN: A cross-sectional study was conducted among 144 female commercial sex workers in Chiang Mai, Thailand. METHODS: The participants were tested for cervical gonorrhea and Chlamydia infection, syphilis, Trichomonas vaginitis, Candida vaginitis, BV, and HIV infection. BV was diagnosed by clinical criteria (pH > 4.5, positive amine test, and presence of clue cells) and using Gram stains. RESULTS: Thirty-three per cent of participants had BV, and 43% were HIV-positive. Using clinical criteria, the association of BV and HIV seropositivity was significant [odds ratio (OR), 2.7; 95% confidence interval (CI), 1.3-5.0]. Although the association between BV and HIV prevalence was not significant using Gram stains alone for diagnosis of BV, an association was found between abnormal vaginal flora and HIV (OR, 2.1; 95% CI, 1.0-4.8). In multiple logistic regression analysis, adjusting for age, number of sexual encounters per week, current condom use, and currently having a sexually transmitted disease (STD), both BV and a history of an STD were independently associated with HIV seropositivity (adjusted OR for BV, 4.0 and 95% CI, 1.7-9.4; adjusted OR for history of an STD, 6.9 and 95% CI, 2.1-22.9). CONCLUSIONS: When diagnosed clinically, BV is independently associated with HIV seroprevalence. HIV infection may promote abnormal vaginal flora, or BV may increase susceptibility to sexual transmission of HIV. Alternatively, the association seen here may result from intervening variables; in this case BV may be a marker or a cofactor of HIV transmission.

AIDS-Related Opportunistic Infections↗
PubMed1995

Phenotypic and genotypic characteristics of human immunodeficiency virus type 1 from patients with AIDS in northern Thailand.

Primary human immunodeficiency virus type 1 (HIV-1) isolates were obtained from 22 patients with AIDS from northern Thailand, where HIV-1 is transmitted primarily through the heterosexual route. Viral sequences were determined for the 22 patients with AIDS, and all were subtype E HIV-1 on the basis of sequence analysis of a region from the envelope protein gp120. Syncytium-inducing (SI) viruses were detected for 16 of 22 patients with AIDS by using MT-2 cells. Characteristics of amino acid sequences in V3 which have not been reported previously for subtype B SI HIV-1 were associated with the subtype E HIV-1 SI phenotype. The SI viruses from our study population contain predominantly a GPGR or GPGH motif at the tip of the V3 loop, in contrast to the previously described subtype E HIV-1 from Thailand which contained predominantly GPGQ. All the SI viruses lost a potential N-linked glycosylation site in V3 which is highly conserved among previously described subtype E HIV-1 isolates from asymptomatic patients from Thailand. HIV-1 envelope sequences including V3 from some patients with AIDS were significantly more divergent than viruses from asymptomatic patients in Thailand characterized 2 years ago or earlier. These results suggest that emergence of subtype E SI HIV-1 variants is associated with the development of AIDS, as it is for subtype B HIV-1. The divergence of subtype E HIV-1 in patients with AIDS as the disease progresses, and the divergence of subtype E HIV-1 in the infected population as the epidemic continues in Thailand, may have important implications for vaccine development.

Acquired Immunodeficiency Syndrome↗
PubMed1995

The phosphotyrosine interaction domain of Shc binds an LXNPXY motif on the epidermal growth factor receptor.

Shc is an SH2 domain protein that is tyrosine phosphorylated in cells stimulated with a variety of growth factors and cytokines. Once phosphorylated, Shc binds the Grb2-Sos complex, leading to Ras activation. Shc can interact with tyrosine-phosphorylated proteins by binding to phosphotyrosine in the context of an NPXpY motif, where pY is a phosphotyrosine. This is an unusual binding site for an SH2 domain protein whose binding specificity is usually controlled by residues carboxy terminal, not amino terminal, to the phosphotyrosine. Recently we identified a second region in Shc, named the phosphotyrosine interaction (PI) domain, and we have found it to be present in a variety of other cellular proteins. In this study we used a dephosphorylation protection assay, competition analysis with phosphotyrosine-containing synthetic peptides, and epidermal growth factor receptor (EGFR) mutants to determine the binding sites of the PI domain of Shc on the EGFR. We demonstrate that the PI domain of Shc binds the LXNPXpY motif that encompasses Y-1148 of the activated EGFR. We conclude that the PI domain imparts to Shc its ability to bind the NPXpY motif.

Adaptor Proteins, Signal Transducing↗
PubMed1995

Carmoxirole inhibits platelet aggregation in vitro and ex vivo.

The influence of carmoxirole, a new antihypertensive DA2-agonist on human platelet aggregation was studied in vitro and ex vivo. In an open study 15 patients with essential hypertension received 3 doses of carmoxirole, 0.5, 1 and 2 mg daily, each for a 2-week period, following a 2-week placebo phase. At the end of each 2-week period blood pressure, platelet aggregation, plasma carmoxirole and plasma catecholamines were measured. Preliminary experiments in vitro showed that 10 microM carmoxirole inhibited the adrenaline induced aggregation velocity by 10%: Increasing the carmoxirole concentration caused dose dependent inhibition which was complete at 1 mM. Carmoxirole itself caused a weak aggregating effect on human platelets in vitro. Blood pressure was reduced from 163 +/- 11/103 +/- 3 before treatment to 155 +/- 11/97 +/- 4, 148 +/- 11/93 +/- 4 and 143 +/- 11/90 +/- 6 mmHg following 2 weeks of 0.5, 1 and 2 mg oral carmoxirole, respectively. Carmoxirole plasma levels 2 1/2 h after the last capsule administration were 0.37 +/- 0.612, 0.95 +/- 1.045 and 3.69 +/- 2.570 ng/ml following treatment with 0.5, 1 and 2 mg carmoxirole, respectively. No influence of carmoxirole on plasma catecholamines could be established. Compared to 100% before treatment, the 5-hydroxytryptamine induced platelet aggregation velocity ex vivo decreased to 70%, 38% and 69% after the administration of 0.5, 1 and 2 mg carmoxirole, respectively. The adrenaline induced aggregation velocity was reduced in the same manner. These results show that carmoxirole is an antihypertensive agent with antithrombotic potential.

Blood Pressure↗
PubMed1995

Platelet aggregation after naftidrofuryl application in vitro and ex vivo.

Naftidrofuryl has been shown to inhibit the interaction between platelets and damaged endothelium, which may lead to thrombosis and is mediated by the 5-hydroxytryptamine. (5-HT2) receptor. This study was designed to investigate the effects of naftidrofuryl on 5-HT induced platelet aggregation. In vitro experiments were carried out on platelets from healthy laboratory personnel. Naftidrofuryl (0.0625-100 microM) caused a continual increase in in vitro inhibition, whereby the inhibition at 0.0625 microM was already significant when compared to control (p < 0.05). The IC50 was approximately 10 microM induced aggregation. Subsequently, ex vivo effects of naftidrofuryl on 5-HT induced platelet aggregation of healthy volunteers together with naftidrofuryl plasma levels were measured. Twelve healthy volunteers received either 400 mg naftidrofuryl or placebo in this double-blind, crossover study. Blood samples for determination of aggregation and naftidrofuryl plasma levels were taken before, 0.5, 1, 2, 3, 4, 5, 6.5 and 9 h after medication application. One hour after application of 400 mg naftidrofuryl a maximal plasma level of approximately 380 ng/ml was measured. Under control conditions the aggregation (Vmax) increased from an arbitrary 100% at 8:00 am to about 150% by 10:00 am, remaining at this level until 5:00 pm. Application of 400 mg naftidrofuryl p.o. resulted in a 50% decrease in Vmax 2 h after drug application. Thereafter, the aggregation rose to the initial 100% value 4 h after drug application and remained at this level during the observation period.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗