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J Johansen

Publications and source records attributed to J Johansen.

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

Chromatin structure and nuclear remodeling.

Nuclear architecture is remodeled during interphase in response to changes in gene activity as well as to changing structural and functional requirements during cell division. Using the monoclonal antibody mAb2A, we have identified two proteins that appear to play important roles in these processes: JIL-1 is a tandem serine-threonine kinase implicated in the regulation of chromatin structure, whereas Skeletor is a novel protein participating in structural nuclear remodeling during the cell cycle. Antibody staining and live imaging of JIL-1-GFP transgenic flies show that JIL-1 localizes to the gene-rich interband regions of larval polytene chromosomes and is upregulated almost twofold on the hypertranscribed male X chromosome compared with autosomes. We propose that JIL-1 may play a role in transcriptional control potentially by regulating chromatin structure. The other mAb2A antigen, Skeletor, is distributed in a nuclear meshwork pattern that can be observed in stereo pair images to reorganize during the cell cycle to form a spindle-like structure at prometaphase that is distinct from the microtubule spindle apparatus. Taking advantage of the powerful molecular and genetic approaches offered in Drosophila, the study of these two proteins promises to yield new insight into what defines nuclear architecture at the molecular level and how its remodeling is regulated.

Amino Acid Sequence↗
PubMed1999

Complex consanguinity associated with short rib-polydactyly syndrome III and congenital infection-like syndrome: a diagnostic problem in dysmorphic syndromes.

Short rib-polydactyly syndromes (SRPS) are a heterogeneous group of recessively inherited lethal skeletal dysplasias. Four types have been recognised. However, overlap in the clinical and radiological features of the four types has led to difficulties in distinguishing between them. The congenital infection-like syndrome is an autosomal recessive syndrome characterised by mental retardation, microcephaly, seizures, and intracranial calcifications. We report a complex consanguineous family of Baluchi origin in whom short rib-polydactyly type III and congenital infection-like syndrome are segregating. Four children inherited SRPS III, one inherited congenital infection-like syndrome, and one inherited both. Although the radiological features in all the children with SRPS in this report were typical of type III, there was overlap in the clinical features with the other types of SRP syndromes. Furthermore, the child who inherited both SRPS III and congenital infection-like syndrome had CNS malformations in addition to periventricular calcification. CNS malformations have been described in SRPS types II and IV but not type III. This report further highlights the overlap between the different types of SRP syndrome. Moreover, it draws attention to the importance of considering the possibility of two recessive syndromes in the same child in complex consanguineous families when features overlap two syndromes.

Abnormalities, Multiple↗
PubMed1998

Describing patients' normal tissue reactions: concerning the possibility of individualising radiotherapy dose prescriptions based on potential predictive assays of normal tissue radiosensitivity. Steering Committee of the BioMed2 European Union Concerted Action Programme on the Development of Predictive Tests of Normal Tissue Response to Radiation Therapy.

Clinical radiotherapeutic doses are limited by the tolerance of normal tissues. Patients given a standard treatment exhibit a range of normal tissue reactions, and a better understanding of this individual variation might allow for individualisation of radiotherapeutic prescriptions, with consequent improvement in the therapeutic ratio. At present, there is no simple way to describe normal tissue reactions, which hampers communication between clinic and laboratory and between groups from different centres. There is also no method for comparing the severity of reactions in different normal tissues. This arises largely because there is no definition of a "normal" reaction, an "extreme" reaction or the particular term "over-reactor" (OR). This report proposes definitions for these terms, as well as a simple terminology for describing normal tissue reactions in patients having radiotherapy. The "normal" range represents the individual variation in normal tissue reactions amongst large numbers of patients treated in the same way which is within clinically acceptable limits. The term "OR" is applied to an individual whose reaction is more severe than the normal range but also implies that this forced a major change in the radiotherapeutic prescription or that the reactions were very severe or fatal. A "severe OR" would develop serious problems with a typical radical dose, while an "extreme OR" would have such difficulties at a much lower dose. To describe the normal range, a numerical scale is suggested, from 1 to 5, resistant to sensitive. The term "highly radiosensitive" (HR) is suggested for category 5. An "informal" relative scale, as suggested here, is quick and simple. It should allow comparison between different hospitals, compensate for differences in radiotherapeutic dose and technique and allow comparison of reactions between different anatomical sites. It should be adequate for discriminating patients at the extremes of the normal range from those at the centre. It is hoped that the definitions and terminology proposed here will aid communication in the field of predictive testing of normal tissue radiosensitivity.

Follow-Up Studies↗
PubMed1998

The neuropeptide Y/agouti gene-related protein (AGRP) brain circuitry in normal, anorectic, and monosodium glutamate-treated mice.

Neuropeptide Y (NPY) and the endogenous melanocortin receptor antagonist, agouti gene-related protein (AGRP), coexist in the arcuate nucleus, and both exert orexigenic effects. The present study aimed primarily at determining the brain distribution of AGRP. AGRP mRNA-expressing cells were limited to the arcuate nucleus, representing a major subpopulation (95%) of the NPY neurons, which also was confirmed with immunohistochemistry. AGRP-immunoreactive (-ir) terminals all contained NPY and were observed in many brain regions extending from the rostral telencephalon to the pons, including the parabrachial nucleus. NPY-positive, AGRP-negative terminals were observed in many areas. AGRP-ir terminals were reduced dramatically in all brain regions of mice treated neonatally with monosodium glutamate as well as of mice homozygous for the anorexia mutation. Terminals immunoreactive for the melanocortin peptide alpha-melanocyte-stimulating hormone formed a population separate from, but parallel to, the AGRP-ir terminals. Our results show that arcuate NPY neurons, identified by the presence of AGRP, project more extensively in the brain than previously known and indicate that the feeding regulatory actions of NPY may extend beyond the hypothalamus.

Animals↗
PubMed1998

Development and pathway formation of peripheral neurons during leech embryogenesis.

By labeling the germinal plates of staged leech embryos with monoclonal antibodies to the immunoglobulin superfamily member Tractin, we have documented the distribution and initial development of peripheral neurons in a hirudinid leech. We find, in addition to sensillar and extrasensillar sensory neurons, that there are 21 identifiable peripheral neurons in each hemisegment. These neurons are found in highly stereotyped positions, and all but two of them are associated with the segmental nerves. We show that eight of the peripheral neurons have the characteristic morphology of stretch receptor neurons and that they form a circumferentially distributed grid aligned in such a way that each of five specialized longitudinal muscle fascicles are monitored by at least two stretch receptor cells covering ventral, lateral, and dorsal regions of the body wall. Furthermore, we show that, in contrast to the dorsal posterior nerve, which is pioneered by central projections, the pathways of the three remaining segmental nerves are likely to be pioneered or guided by peripheral neurons.

Animals↗
PubMed1998

Posterior capsule opacification and neodymium: YAG capsulotomy with heparin-surface-modified intraocular lenses.

PURPOSE: To compare the effect of heparin-surface-modified (HSM) and conventional unmodified poly(methyl methacrylate) (PMMA) intraocular lenses (IOLs) on the formation of posterior capsule opacification (PCO). SETTING: Department of Ophthalmology, Vejle Hospital, Denmark. METHODS: This prospective, randomized, double-blind study comprised 250 eyes of 246 patients who had uneventful extracapsular cataract extraction in otherwise healthy eyes with implantation of a biconvex IOL or a convex-plano lens with a continuous laser ridge. Patients were examined once a year for 3 years, at which time the degree of PCO was recorded. A neodymium:YAG laser capsulotomy was performed if certain criteria were met. RESULTS: The incidence of PCO was statistically significantly higher in eyes with an HSM convex-plano laser-ridge IOL than in those with an unmodified convex-plano lens (P < .005). There were no significant differences between any other groups. CONCLUSION: The incidence of PCO was higher in eyes with an HSM convex-plano IOL with a laser ridge.

Aged↗
PubMed1998

Radiosensitivity of normal fibroblasts from breast cancer patients assessed by the micronucleus and colony assays.

PURPOSE: To investigate whether radiation-induced micronucleus formation as expressed by the cytochalasin-blocked Mn-assay correlates with cellular radiosensitivity measured by a colony assay in primary fibroblast cultures from cancer patients. MATERIALS AND METHODS: Studies were made on skin fibroblasts from 36 breast cancer patients. The micronucleus assay was performed using treatment with cytochalasin-B to create binucleate cells. Response was scored in terms of the percentage of binucleate cells with micronuclei, also as the number of micronuclei per binucleate cell. The data were related to previously published results of cell survival measurements on these cell lines. RESULTS: Neither endpoint for micronucleus formation showed a correlation with radiosensitivity by the colony assay. The fraction of fibroblasts that reach mitosis without micronuclei also failed to correlate with cell survival. CONCLUSIONS: Among these primary fibroblast cell lines radiation-induced micronucleus formation was not associated with radiosensitivity as measured by a colony assay.

Adult↗
PubMed1998

Severity of respiratory syncytial virus disease related to type and genotype of virus and to cytokine values in nasopharyngeal secretions.

BACKGROUND: Investigations concerning the severity of respiratory syncytial virus (RSV) disease as related to (1) RSV type and genotype determined respectively by PCR and restriction enzyme analysis and (2) interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) values in samples of nasopharyngeal secretion (NPS) have not been previously reported. METHODS: We prospectively studied 105 RSV infections in the lower respiratory tract of infants and young children admitted to a pediatric department in Copenhagen during three winter seasons, 1993, 1994 and 1995. RSV strains were typed and genotyped, respectively, by PCR and nucleic acid restriction analysis and correlated to the severity of the disease. The ratio IL-6:TNF-alpha, determined from IL-6- and TNF-alpha values in samples of NPS, was related to the severity of the disease. Concentrations of IL-6 and of TNF-alpha were determined in serum samples taken during 5 weeks after the onset of illness. RESULTS: Type B infections produced more severe disease than did type A infections, as assessed on the length of the hospital stay, use of respiratory support and the presence of an infiltrate on a chest radiograph. This difference was age-related. It was observed in infants 0 to 5 months old, but not in older age groups. Type B genotype B1122 produced more severe disease than type A genotype A2311 in infants 0 to 11 months old. Increased serum concentrations of IL-6 and TNF-alpha were detected in samples taken 1 to 2 days after the onset of illness. Whereas TNF-alpha serum concentrations remained high, IL-6 serum concentrations decreased during the following 3 to 4 weeks. The IL-6:TNF-alpha ratio in samples of NPS was related to the severity of the disease. A high ratio was related to a low severity. CONCLUSIONS: The severity of disease in patients admitted with acute RSV infections can be correlated to the RSV type as determined by PCR, to the RSV genotype as determined by nucleic acid restriction analysis and to the ratio IL-6:TNF-alpha in NPS.

Child, Preschool↗
PubMed1997

Hypothalamic neurohistochemistry of the murine anorexia (anx/anx) mutation: altered processing of neuropeptide Y in the arcuate nucleus.

Neuropeptide Y is one of the most powerful neurochemical stimulants of food intake known. The neuronal substrate for this action is believed to be the neuropeptide Y-expressing cell population in the hypothalamic arcuate nucleus. In this study, mice homozygous for the anorexia mutation (anx) were investigated histochemically; anx is a recessive mutation that causes decreased food intake and starvation, leading to death 22 days after birth. We were interested to see whether any hypothalamic neurochemical abnormalities could be detected in this genetic model of starvation. By using immunohistochemistry and in situ hybridization, the hypothalamic distributions of neuropeptide Y, cholecystokinin, galanin, and serotonin, all messenger molecules postulated to be involved in the regulation of food intake and energy metabolism, were investigated. Immunoreactivities for somatostatin, the excitatory amino acid aspartate, and acetylcholinesterase were also studied. Neuropeptide Y-like immunoreactivity was increased markedly in arcuate cell bodies and decreased in terminals in the arcuate nucleus and other hypothalamic regions of anx/anx mice compared with normal litter mates. In situ hybridization for neuropeptide Y mRNA, however, showed no significant difference in gene expression in the arcuate nucleus. In addition, immunoreactivities for aspartate, acetylcholinesterase, and somatostatin in the arcuate nucleus were decreased in anx/anx mice. For cholecystokinin, galanin, and serotonin, no certain differences in hypothalamic immunoreactivity could be seen. These data suggest that a defect in neuropeptide Y-ergic signalling in the arcuate neurons may contribute to the failure to thrive in anx/anx mice.

Animals↗
PubMed1997

Differential glycosylation of tractin and LeechCAM, two novel Ig superfamily members, regulates neurite extension and fascicle formation.

By immunoaffinity purification with the mAb Lan3-2, we have identified two novel Ig superfamily members, Tractin and LeechCAM. LeechCAM is an NCAM/FasII/ApCAM homologue, whereas Tractin is a cleaved protein with several unique features that include a PG/YG repeat domain that may be part of or interact with the extracellular matrix. Tractin and LeechCAM are widely expressed neural proteins that are differentially glycosylated in sets and subsets of peripheral sensory neurons that form specific fascicles in the central nervous system. In vivo antibody perturbation of the Lan3-2 glycoepitope demonstrates that it can selectively regulate extension of neurites and filopodia. Thus, these experiments provide evidence that differential glycosylation can confer functional diversity and specificity to widely expressed neural proteins.

Amino Acid Sequence↗
PubMed1997

Contrast sensitivity with silicone and poly(methyl methacrylate) intraocular lenses.

PURPOSE: To compare the optical performance of silicone intraocular lenses (IOLs) with that of conventional poly(methyl methacrylate) (PMMA) IOLs. SETTING: University hospital outpatient cataract clinic. METHODS: Ninety-one patients were randomly assigned to receive a PMMA IOL (n = 48 eyes) or a silicone IOL (n = 43 eyes). Contrast sensitivity was evaluated 4 months after surgery using the Vistech sinusoidal-grating chart and the Pelli-Robson letter sensitivity chart. RESULTS: No between-group differences were found using the Vistech test. Using the Pelli-Robson test, mean uncorrected contrast sensitivity was 1.59 log units +/- 0.13 (SD) in the PMMA group and 1.53 +/- 0.15 log units in the silicone group. Mean best corrected contrast sensitivity was 1.67 +/- 0.11 and 1.63 +/- 0.16, respectively. The differences between groups using the Pelli-Robson test were statistically significant (P < .05). No correlation was found between reduced contrast sensitivity and brownish discoloration or thickness of silicone IOLs or posterior capsule fibrosis. CONCLUSION: Contrast sensitivity was lower in patients with silicone IOLs than in those with conventional PMMA lenses.

Adult↗
PubMed1997

Cooperation of B cells and T cells is required for survival of mice infected with vesicular stomatitis virus.

To define the role of T cells and B cells in resistance to vesicular stomatitis virus (VSV) infection, knockout mice with different specific immune defects on an identical background were infected i.v. and the outcome of infection was compared; in this way a more complete picture of the relative importance of various host defence mechanisms could be obtained. Compared to T and B cell-deficient SCID mice which all succumbed from encephalitis within 5-9 days of infection, T cell-deficient nude mice generally lived longer, but within a period of approximately 1 month after challenge all died. In contrast, B cell-deficient mice were highly susceptible even to low doses of virus and mortality could be prevented by transfer of naive B cells prior to challenge as well as by immune serum given after challenge. Analysis of MHC class I- and class II-deficient mice revealed that CD8+ T cells could exert some antiviral activity, but CD4+ T cells sufficed for survival and were required for optimal resistance. Consistent with this it was found that in nude mice a lethal outcome could be prevented by transfer of CD8-depleted cells from B cell-deficient mice. Thus our results clearly demonstrate that while antibodies are pivotal for survival in the early phase of VSV infection, T cells are required for long-term survival, with CD4+ T cells being more effective in controlling this infection than CD8+ T cells.

Animals↗
PubMed1997

Restriction pattern variability of respiratory syncytial virus during three consecutive epidemics in Denmark.

A PCR-based assay was used to distinguish between respiratory syncytial virus (RSV) group A and B in order to analyze their prevalence in Denmark in three consecutive epidemics during the winters of 1992/93, 1993/94 and 1994/95. A total of 96 RSV strains isolated from hospitalized children were examined, showing alternation of group prevalence. Furthermore, the genetic variability of the RSV isolates was illustrated by restriction enzyme analysis of PCR products originating from a part of the F and G proteins that has been reported to be highly variable. We found that, in general, different genome types predominated each year, some types being present in consecutive epidemics, indicating a contribution of strains circulating unattended between outbreak seasons, while others seemed to disappear or became undetectable, being replaced by emerging types. Some of the genome types found seemed related to strains isolated up to more than two decades ago in other parts of the world. This indicates that the temporal fluctuation in predominance of genome types presumably caused by selective pressure exerted by host immunity is due to the favoring of strains from a pool of globally circulating, genetically relatively stable genome types, rather than a molecular evolution in strains induced or directed by immunoselective pressure.

Animals↗
PubMed1997

Improved body composition after 8 wk of electrically stimulated leg cycling in tetraplegic patients.

The practical aspects of utilizing electrically stimulated leg cycling (ESLC) to counteract alterations in body composition were investigated in five tetraplegic subjects with long-standing complete spinal cord injuries (C5-C7). After a 2-wk adaptation period, the subjects performed seven ESLC sessions per week for 8 wk. No adverse reactions were noted in response to the ESLC program. The ESLC sessions were accompanied by higher lactate concentrations compared with arm exercise. Heart rate and blood pressure response revealed clear, but not serious, signs of autonomic dysreflexia in the beginning of the ESLC sessions. Body temperature increased moderately during the ESLC sessions. Peak oxygen uptake (Vo2) during an ESLC session increased by 70% (P < 0.05) after 8 wk of training. Body composition, evaluated by dual-energy X-ray absorptiometry (DEXA), demonstrated an increase in lean body mass (LBM) from 66.2 +/- 2.6 to 68.2 +/- 2.1% (P < 0.05), with a concomitant decrease in whole body fat (BF) content from 29.7 +/- 2.6 to 27.8 +/- 2.1% (P < 0.05) after training. The cross-sectional area of quadriceps, hamstrings, gluteus maximus, and gluteus medius muscles, measured by computer tomographic scans, increased from 267 +/- 27 to 324 +/- 27 cm2 (P < 0.05) after the training. In conclusion, daily ESLC sessions during a 2-mo period resulted in increased LBM, decreased BF content, and increased muscular endurance in tetraplegic subjects without any noticeable adverse effects.

Absorptiometry, Photon↗
PubMed1997

Molecular mechanisms mediating axon pathway formation.

During nervous system formation nerve cells extend axons in order to form precise patterns of neuronal connectivity. These connections are often established after the neuronal growth cones have pioneered or navigated through complex pathways to their target area both within the CNS and to and from the periphery. Recent studies have provided evidence that the process of specific pathway formation may rely on a number of molecular guidance mechanisms and cues such as selective adhesion, growth cone avoidance, surface gradients, guidepost cells, and chemotropism. Analysis of the molecular basis for these guidance mechanisms show that the molecules involved often belong to distinct multigene families and that they can provide both short- and long-range attractive as well as repulsive cues. Many of these molecules have a modular structure that is made up of different tandemly arranged domains that allow for multiple functional interactions with a range of other molecules. This allows the same molecule to be multifunctional, for example, by attracting certain neurons while repelling others. This review is an overview of the molecular structure, as it relates to function and mechanisms of action of some of the major gene families thought to be mediating specific axonal guidance and pathway formation.

Animals↗
PubMed1997

Predictors of adolescent psychopathy: oppositional and conduct-disordered symptoms.

Psychopathy is an important clinical construct in the evaluation and treatment of adolescent offenders. In this study, predictors of adolescent psychopathy are explored in 81 adolescents from a residential treatment program for dually diagnosed offenders. The number of aggressive conduct disorder symptoms and total rate (number x frequency of symptoms) of deceit/theft symptoms are predictive of adolescent psychopathy. Although age of onset for conduct disorder symptoms is associated with psychopathy, its interpretation appears to be confounded by gender and ethnicity correlates. Unexpectedly, adolescent psychopathy was only modestly associated with institutional infractions. Past research and current findings are summarized with reference to their forensic implications.

Adolescent↗
PubMed1997

Accuracy of single-voxel proton MR spectroscopy in distinguishing neoplastic from nonneoplastic brain lesions.

PURPOSE: To measure the accuracy of single-voxel, image-guided proton MR spectroscopy in distinguishing normal from abnormal brain tissue and neoplastic from nonneoplastic brain disease. METHODS: MR spectroscopy was performed at 0.5 T with the point-resolved spectroscopic pulse sequence and conventional postprocessing techniques. Subjects consisted of a consecutive series of patients with suspected brain neoplasms or recurrent neoplasia and 10 healthy adult volunteers. Fifty-five lesions in 53 patients with subsequently verified final diagnoses were included. Spectra were interpreted qualitatively by visual inspection by nonblinded readers (prospectively) with the benefit of prior clinical data and imaging studies, and by blinded readers (retrospectively). The nonblinded readers interpreted the spectra as diagnostic or not, and, if diagnostic, as neoplastic or nonneoplastic. The blinded readers classified the spectra as diagnostic or not, and, if diagnostic, as normal or abnormal and as neoplastic or nonneoplastic (when abnormal). The sensitivity, specificity, positive and negative predictive values, and accuracy were calculated from blinded and nonblinded MR spectroscopy interpretations. A receiver operator characteristic (ROC) curve analysis was performed on blinded MR spectroscopy interpretations. RESULTS: The diagnostic accuracy averaged across four blinded readers in differentiating patients from control subjects was .96, while the area under the aggregate (pooled interpretations) ROC curve approached unity. Accuracy in the nonblinded and blinded discrimination of neoplastic from nonneoplastic disease was .96 and .83, respectively. The area under the aggregate ROC curve in the blinded discrimination of neoplasm from nonneoplasm was .89. CONCLUSIONS: Image-guided proton spectra obtained at 0.5 T from patients with suspected neoplasia can be distinguished from spectra in healthy control subjects, and neoplastic spectra can be distinguished from nonneoplastic spectra with a high degree of diagnostic accuracy.

Adult↗