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Biomedical subjects

J E Johnson

Publications and source records attributed to J E Johnson.

At least 91 records · Page 5Linked to original sources
PubMed1999

Overexpression of brain-derived neurotrophic factor enhances sensory innervation and selectively increases neuron number.

Target-derived neurotrophin growth factors have significant effects on the development and maintenance of the mammalian somatosensory system. Studies of transgenic mice that overexpress neurotrophins NGF and neurotrophin 3 (NT-3) at high levels in skin have shown increased sensory neuron number and enhanced innervation of specific sensory ending types. The effects of two other members of this family, BDNF and NT-4, on sensory neuron development are less clear. This study examined the role of brain-derived neurotrophic factor (BDNF) using transgenic mice that overexpress BDNF in epithelial target tissues of sensory neurons. BDNF transgenic mice had an increase in peripheral innervation density and showed selective effects on neuron survival. Neuron number in trigeminal ganglia, DRG, and SCG were unchanged, although a 38% increase in neurons comprising the placode-derived nodose-petrosal complex occurred. BDNF transgenic skin showed notable enhancement of innervation to hair follicles as detected by PGP9.5 immunolabeling. In nonhairy plantar skin, Meissner corpuscle sensory endings were larger, and the number of Merkel cells with associated innervation was increased. In trigeminal ganglia, neurons expressing trkB receptor were increased threefold, whereas trkA-positive neurons doubled. Analysis of trkB by Northern, reverse transcription-PCR, and Western assays indicated a modest increase in the expression of the T1 truncated receptor and preferential distribution to the periphery. These data indicate that skin-derived BDNF does not enhance survival of cutaneous sensory neurons, although it does promote neurite innervation of specific sites and sensory end organs of the skin.

Animals↗
PubMed1999

An animal virus-derived peptide switches membrane morphology: possible relevance to nodaviral transfection processes.

The N-terminal domain of the capsid protein cleavage product of the flock house virus (FHV) consists of 21 residues and forms an amphipathic alpha-helix, which is thought to play a crucial role in permeabilizing biological membranes for RNA translocation in the host cell. We have found that the Met --> Nle variant of this domain (denoted here as gamma1) efficiently induces the formation of the interdigitated gel phase (LbetaI) of 1, 2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) bilayers. In situ scanning force microscopy of solid supported bilayers and fluorescence spectroscopy of peptide-treated DPPC vesicles provide evidence for the formation of acyl chain interdigitated lipid domains. It could be shown by fluorescence spectroscopy that the peptide inserts in the DPPC matrix above the main transition temperature of the lipid, while the formation of domains with decreased thickness occurs after the sample is cooled to 25 degrees C. The orientation and secondary structure of the peptide in lipid bilayers were investigated using attenuated total reflectance infrared (ATR-IR) and circular dichroism (CD) spectroscopy. These results enabled us to formulate a mechanistic model for the peptide-mediated induction of interdigitation in DPPC bilayers. Moreover, the membrane activity of gamma1 with gel phase lipids established in this study may have further implications for the infection strategy adopted by simple RNA viruses.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1999

Virus assembly: Imaging a molecular machine.

A recent structural study of a double-stranded DNA bacteriophage has provided remarkable new insights into the assembly of a complex virus particle and ushers in a new era in the imaging of non-icosahedral viruses.

Bacillus Phages↗
PubMed1999

Product review: lucis image processing software.

Lucis is a software program that allows the manipulation of images through the process of selective contrast pattern emphasis. Using an image-processing algorithm called Differential Hysteresis Processing (DHP), Lucis extracts and highlights patterns based on variations in image intensity (luminance). The result is that details can be seen that would otherwise be hidden in deep shadow or excessive brightness. The software is contained on a single floppy disk, is easy to install on a PC, simple to use, and runs on Windows 95, Windows 98, and Windows NT operating systems. The cost is $8,500 for a license, but is estimated to save a great deal of money in photographic materials, time, and labor that would have otherwise been spent in the darkroom. Superb images are easily obtained from unstained (no lead or uranium) sections, and stored image files sent to laser printers are of publication quality. The software can be used not only for all types of microscopy, including color fluorescence light microscopy, biological and materials science electron microscopy (TEM and SEM), but will be beneficial in medicine, such as X-ray films (pending approval by the FDA), and in the arts.

Algorithms↗
PubMed1999

Respiratory syncytial virus infection prolongs methacholine-induced airway hyperresponsiveness in ovalbumin-sensitized mice.

Severe respiratory syncytial virus (RSV)-induced disease is associated with childhood asthma and atopy. We combined models of allergen sensitization and RSV infection to begin exploring the immunologic interactions between allergic and virus-induced airway inflammation and its impact on airway hypersensitivity. Airway resistance was measured after methacholine challenge in tracheally intubated mice by whole body plethysmography. Lung inflammation was assessed by bronchoalveolar lavage (BAL) and histopathology. RSV infection alone did not cause significant airway hyperresponsiveness (AHR) to methacholine. Ovalbumin (OVA)-induced AHR lasted only a few days past the discontinuance of OVA aerosol in mice that were ovalbumin sensitized and mock infected. In contrast, OVA-sensitized mice infected with RSV during the OVA aerosol treatments (OVA/RSV) had AHR for more than 2 weeks after infection. However, 2 weeks after either RSV or mock infection, OVA/RSV mice had significantly more lymphocytes found during BAL than OVA mice, whereas the OVA and OVA/RSV groups had the same number of eosinophils. Histopathologic analysis confirmed an increased inflammation in the lungs of OVA/RSV mice compared with OVA mice. In addition, OVA/RSV mice had a more widespread distribution of mucus in their airways with increased amounts of intraluminal mucus pools compared with the other groups. Thus, prolonged AHR in RSV-infected mice during ovalbumin-sensitization correlates with increased numbers of lymphocytes in BAL fluid, increased lung inflammation, and mucus deposition in the airways, but not with airway eosinophilia. A further understanding of the immunologic consequences of combined allergic and virus-induced airway inflammation will impact the management of diseases associated with airway hyperreactivity.

Animals↗
PubMed1999

Self-regulation theory and coping with physical illness.

A self-regulation theory of how patients cope with events that occur during physical illness that has received substantial support from research is described. The theory challenges some traditional thinking about providing patients information and patients' emotional responses to threatening health care events. The use of the theory in practice and suggestions for research to further develop the theory are discussed.

Adaptation, Psychological↗
PubMed1999

Pulmonary vascular morphological changes in cirrhotic patients undergoing liver transplantation.

Cirrhosis and portal hypertension may be associated with pulmonary hypertension and pulmonary dysfunction. However, morphological pulmonary vascular lesions in patients with cirrhosis have not been well characterized morphometrically. We morphometrically evaluated pulmonary vessels in liver transplant recipients with pretransplantation cirrhosis and correlated our findings with pretransplantation cardiopulmonary function, postoperative course, and postmortem cardiopulmonary findings. Autopsy lung slides from 23 transplant recipients with pretransplantation cirrhosis were examined. External vessel diameter, intimal thickness, and arterial medial thickness were measured with a micrometer after pentachrome staining. The percent of total diameter comprised by intima or media was calculated for each vessel. Medical records were reviewed for smoking history, pretransplantation cardiopulmonary function testing, and postoperative course. Autopsy cases without liver or significant cardiopulmonary diseases, matched for age, sex, and smoking history, served as controls. Transplant recipients had significantly more pulmonary venous intimal thickening than matched controls (P <.0001). Sixty-five percent (15 of 23) of these patients had some degree of pretransplantation pulmonary dysfunction, defined by abnormalities in pulmonary function tests, oxygen saturation, and/or increased pulmonary artery pressures. However, the severity of venous intimal thickening did not correlate with the severity of pretransplantation pulmonary dysfunction. Arterial intimal and medial thickness were not statistically significantly different from controls. Pulmonary venous intimal thickening and resultant luminal impingement are morphological findings not previously described in this population. The arterial lesion, when present, is similar to that seen in pulmonary hypertension from other causes. These pulmonary vascular lesions may be implicated in pulmonary dysfunction in patients with cirrhosis and may be associated with increased posttransplantation cardiopulmonary morbidity and mortality.

Adult↗
PubMed1999

Control of air quality in an assisted reproductive technology laboratory.

OBJECTIVE: To investigate the effect of improved air quality on IVF and subsequent embryo development. DESIGN: Retrospective cohort study. SETTING: Hospital-based IVF facility composed of an anteroom, a cleanroom, and an adjacent operating room. PATIENT(S): Two-hundred seventy-five couples requesting IVF between 1993 and 1997. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Particle counts (sizes 0.3, 0.5, 1.0, and 5.0 microm); IVF rates; and embryo quality (stage and grade). RESULT(S): Clinical pregnancy rates decreased from 35% in 1993 to 16% in 1994 (numerous construction odors were detected during 1994) and increased steadily after the cleanroom was built (rates for 1995-1997 were 20%, 32%, and 59%, respectively). Fertilization rates decreased between 1993 (74%) and 1994 (60%) and then steadily increased after cleanroom installation (62% in 1995, 71% in 1996, and 69% in 1997). The proportion of embryos past the four-cell stage decreased from 66% in 1993 to 61% in 1994 but then increased steadily in the years after the cleanroom was built (78%, 77%, and 83% in 1995, 1996, and 1997, respectively). During the same 5-year period, there were no differences in embryo quality or number of embryos transferred. CONCLUSION(S): Construction of a Class 100 cleanroom improved air quality and IVF rate and increased the number of embryos past the four-cell stage available for transfer.

Adult↗
PubMed1999

A highly membrane-active peptide in Flock House virus: implications for the mechanism of nodavirus infection.

BACKGROUND: Nodaviruses are among the simplest animal viruses, and are therefore attractive systems for deconvoluting core viral processes such as assembly, infection and uncoating. Membrane translocation of the single-stranded RNA genome of nodaviruses has been proposed to be mediated by direct lipid-protein interactions between a post-assembly autocatalytic cleavage product from the capsomere and the target membrane. To probe the validity of this hypothesis, we have synthesized a 21-residue Met-->Nle (norleucine) variant of the amino-terminal helical domain (denoted here as gamma1) of the cleavage peptide in Flock House nodavirus (FHV) and studied its ability to alter membrane structure and function. RESULTS: The synthetic peptide gamma1 increases membrane permeability to hydrophilic solutes, as judged by fluorescence experiments with liposome-encapsulated dyes and ion-conductance measurements. Furthermore, peptide orientation and location within lipid bilayers was determined using tryptophan-fluorescence-quenching experiments and attenuated total reflectance infrared spectroscopy. CONCLUSIONS: The helical domain of the FHV cleavage product partitions spontaneously into lipid bilayers and increases membrane permeability, consistent with the postulated mechanism for viral genome translocation. The existence of a membrane-binding domain in the FHV cleavage sequence suggests peptide-triggered disruption of the endosomal membrane as a prelude to viral uncoating in the host cytoplasm. A model for this interaction is proposed.

Amino Acid Sequence↗
PubMed1999

The crystal structure of cricket paralysis virus: the first view of a new virus family.

Numerous small, RNA-containing insect viruses are currently classified as picornaviruses, or as 'picorna-like', since they superficially resemble the true picornaviruses. Considerable evidence now suggests that several of these viruses are members of a distinct family. We have determined the gene sequence of the capsid proteins and the 2.4 A resolution crystal structure of the cricket paralysis virus. While the genome sequence indicates that the insect picorna-like viruses represent a distinct lineage compared to true picornaviruses, the capsid structure demonstrates that the two groups are related. These viral genomes are, thus, best viewed as composed of exchangeable modules that have recombined.

Amino Acid Sequence↗
PubMed1999

Prophylaxis with respiratory syncytial virus F-specific humanized monoclonal antibody delays and moderately suppresses the native antibody response but does not impair immunity to late rechallenge.

Respiratory syncytial virus (RSV) is the most significant viral cause of lower respiratory tract disease in infants and children. This study tested the hypothesis that a humanized murine monoclonal antibody (MAb) would protect against RSV infection in mice and have minimal suppressive effect upon the immune response because it is directed against a single epitope. A humanized murine MAb (RSHZ19) was tested for both prophylaxis and treatment of RSV infection in BALB/c mice and compared with a polyclonal product. Mice were rechallenged when passively administered antibody was undetectable (day 104). RSHZ19 reduced virus titer and protected against illness when used in prophylaxis and effected rapid virus clearance when used as treatment. Polyclonal antibody was also an effective prophylaxis but required 200 times the dose in total protein. Peak neutralizing antibody responses were delayed and somewhat suppressed in the prophylactically treated groups, but mice were protected against infection on rechallenge. Secondary antibody response to rechallenge in passively immunized mice was equal to that in untreated mice.

Animals↗
PubMed1999

Mania in the geriatric patient population: a review of the literature.

The diagnosis of mania in the geriatric population is uncommon. However, it comprises significant healthcare utilization and cost requirements, which are expected to increase in the near future with the projected increase in the geriatric population. The authors review literature pertaining to geriatric mania and discuss epidemiology, psychopathology, neuropathology, differential diagnosis, evaluation, treatment, and outcomes. Literature searches were performed by GratefulMed for the years 1960-1997, with secondary- and tertiary-source follow-up. It is clear from this review that geriatric mania is a complex illness with many possible etiologies and treatments. Much more research needs to be conducted in all of the areas reviewed.

Age of Onset↗
PubMed1999

Evaluation of pulmonary function in workers exposed to hexamethylene diisocyanate.

Production of hexamethylene diisocyanate (HDI) biuret and trimer from HDI monomer was started in 1988 at the plant under study. Pulmonary function tests were included as part of the annual evaluation of the workers in that unit. HDI is expected to have toxic properties similar to those of toluene diisocyanate. The latter has caused accelerated declines in pulmonary function in exposed workers. In 1991, an initial longitudinal evaluation of those pulmonary function tests was performed, comparing annual declines in forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1). The purpose of the study was to evaluate whether or not exposures to HDI at the unit had caused any accelerated decline in FVC or FEV1. No significant differences were seen in that evaluation, but it was decided that the study be continued in a prospective fashion. The study has been continued through 1997. The slope of the annual change in FVC and FEV1 were calculated for a group of workers and a matched control group. The average annual decline in FVC for the exposed group (cases) was 0.026 L, compared with 0.025 L for the control group. For the decline in FEV1, the results were 0.044 L, compared with 0.041 L (P = 0.79). These results are virtually identical and support a conclusion that exposures within this unit to HDI have not caused an accelerated decline in FVC or FEV1. Exposures to HDI were measured during this period. The time-weighted average exposure to HDI during work not requiring respiratory protection in the unit (approximately 2 hours per day) was 0.5 parts per billion. The average daily high peak exposure was 2.9 parts per billion. Exposure to these levels appear to pose no risk of accelerated decline in pulmonary function.

Adult↗
PubMed1999

Pseudomonas aeruginosa outer-membrane protein F epitopes are highly immunogenic in mice when expressed on a plant virus.

A synthetic peptide (peptide 10) representing a surface-exposed, linear B cell epitope from outer-membrane (OM) protein F of Pseudomonas aeruginosa was shown previously to afford protection in mice from P. aeruginosa infection. This peptide was expressed in tandem with the protein F peptide 18 on each of the two coat proteins of cowpea mosaic virus (CPMV). The chimaeric virus particles (CVPs) expressing the peptides on the S (small) coat protein (CPMV-PAE4) and L (large) coat protein (CPMV-PAE5) were used to immunize mice. Following subcutaneous immunization in Freund's and QuilA adjuvants, CPMV-PAE4 induced antibodies predominantly against peptide 18, whereas CPMV-PAE5 produced antibodies exclusively against peptide 10, indicating that the site of peptide expression on CPMV influences its immune recognition. The anti-peptide antibodies elicited by CPMV-PAE5 were predominantly of the IgG2a isotype, indicating a highly polarized TH1-type response. The peptide-specific IgG2a strongly recognized the whole F protein, but more importantly, recognized protein F in all seven Fisher-Devlin immunotypes of P. aeruginosa. Furthermore, the peptide-specific IgG2a in CVP/QS-21 adjuvant-immunized mice was shown to bind complement and to augment phagocytosis of P. aeruginosa by human neutrophils in vitro. The ability of CPMV-PAE5 to induce P. aeruginosa-specific opsonic IgG2a gives it potential for further development as a protective vaccine against P. aeruginosa.

Animals↗
PubMed1999

Crystallographic analysis of the dsDNA bacteriophage HK97 mature empty capsid.

HK97 is a member of the Siphovirus family of dsDNA bacteriophages. It is similar in architecture to bacteriophage lambda, the type member of this family, with an icosahedral capsid of triangulation number T = 7. No high-resolution structural information is available for the dsDNA phages, and HK97 is the only dsDNA bacteriophage capsid to produce crystals which diffract X-rays. At 650 A in diameter, the large size of the particle and resultant large unit cell create crystallographic challenges. The empty Head II (mature) particles were expressed in Escherichia coli and assembled in vitro, but they have the same morphology as the mature HK97 capsid. Previously reported Head II crystals diffracting to 3.5 A resolution are examined here in detail. Although the cell dimensions suggest an orthorhombic lattice, further analysis demonstrated that the space group was monoclinic. This has been confirmed by the present study. Images were recorded on the F1 beamline at CHESS and they were processed and scaled, resulting in a data set with a cumulative completeness of 65% and a scaling R factor of 7.7% to 7 A. The cell dimensions after post-refinement were a = 580, b = 626, c = 788 A, beta = 90.0 degrees. From the particle dimensions determined by cryo-electron microscopy (cryo-EM), there were determined to be two particles per unit cell. Systematic absences of even reflections along the 0k0 lattice line indicate that the space group is P21. The rotation function was used to determine the orientation of the particles in the unit cell and to confirm the space group. An icosahedral twofold axis is approximately, but not exactly, aligned with the crystallographic screw (b) axis. An icosahedral twofold axis orthogonal to the one approximately parallel to the b axis, is rotated 18 degrees away from the a axis. The centers of the two particles must be positioned close to the minimum-energy packing arrangement for spheres, which places one particle at ((1/4), 0, (1/4)) and the other particle at ((3/4), (1/2), (3/4)). The particle position and orientation were confirmed by calculating a Patterson function. The particles interact closely along icosahedral threefold axes, which occurs both along the crystallographic a axis and along the b axis. The particle dimensions derived from this packing arrangement agree well with those determined by cryo-EM and image reconstruction. The cryo-EM reconstruction will be used as a model to initiate phase determination; structure determination at 7 A is under way.

Bacteriophages↗
PubMed1999

Replication-competent rhabdoviruses with human immunodeficiency virus type 1 coats and green fluorescent protein: entry by a pH-independent pathway.

We describe a replication-competent, recombinant vesicular stomatitis virus (VSV) in which the gene encoding the single transmembrane glycoprotein (G) was deleted and replaced by an env-G hybrid gene encoding the extracellular and transmembrane domains of a human immunodeficiency virus type 1 (HIV-1) envelope protein fused to the cytoplasmic domain of VSV G. An additional gene encoding a green fluorescent protein was added to permit rapid detection of infection. This novel surrogate virus infected and propagated on cells expressing the HIV receptor CD4 and coreceptor CXCR4. Infection was blocked by SDF-1, the ligand for CXCR4, by antibody to CD4 and by HIV-neutralizing antibody. This virus, unlike VSV, entered cells by a pH-independent pathway and thus supports a pH-independent pathway of HIV entry. Additional recombinants carrying hybrid env-G genes derived from R5 or X4R5 HIV strains also showed the coreceptor specificities of the HIV strains from which they were derived. These surrogate viruses provide a simple and rapid assay for HIV-neutralizing antibodies as well as a rapid screen for molecules that would interfere with any stage of HIV binding or entry. The viruses might also be useful as HIV vaccines. Our results suggest wide applications of other surrogate viruses based on VSV.

Animals↗
PubMed1999

Fibular nonunion and equinovarus deformity secondary to posterior tibial tendon incarceration in the syndesmosis: a case report after a bimalleolar fracture-dislocation.

A 39-year-old woman sustained a grade II open bimalleolar fracture-dislocation of the left ankle. Six months after an ORIF of these fractures was performed, she presented with a nonunion of the distal fibula fracture and with a fixed hindfoot equinovarus and forefoot adduction deformity. At surgery for repair of the fibular nonunion, the posterior tibial tendon (PTT) was found to be entrapped in the posterior tibiotalar joint, with a portion of the tendon interposed between the tibia and the fibula in the area of the posterior syndesmosis. After extrication of the PTT, the hindfoot varus and forefoot adduction deformity were corrected. To our knowledge, this is the first case report in the English literature of a missed PTT syndesmotic entrapment that resulted in a fibular nonunion and in a fixed foot deformity after an open bimalleolar ankle fracture dislocation.

Adult↗