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Biomedical subjects

L Olsen

Publications and source records attributed to L Olsen.

At least 55 records · Page 3Linked to original sources
PubMed1996

Alterations in neurotrophin and neurotrophin-receptor localization in Hirschsprung's disease.

Interactions of the trk family of tyrosine kinase receptors with neurotrophins promote growth and differentiation of nervous-system cells during development. Disturbances in neurotrophic signalling could be involved in functional or aganglionic conditions of the intestine such as Hirschsprung's disease (HD). Intestinal resection specimens from 20 children with HD and from 10 normal age-matched controls were evaluated immunocytochemically for the presence of TrkA, TrkB, and TrkC protein, and the neurotrophin ligands brain-derived neurotrophic factor [BDNF] and neurotrophin-3 (NT-3). All three neurotrophin receptors are localized with cellular specificity to the enteric nervous system of normal and proximal ganglionic HD intestine; however, none was detected in the hypertrophic nerve fibers of aganglionic HD segments. Aganglionic HD intestine lacked intense and specific TrkC and BDNF enteric ganglionic immunoreactivity. NT-3, localized to enteric plexuses and basal lamina of ganglionic intestine, was not detected in ganglion cells located at the "transitional zone" of HD intestine. These data suggest that neurotrophic influences may be involved in enteric nervous-system cellular survival and differentiation in functional intestinal disorders such as HD.

Brain-Derived Neurotrophic Factor↗
PubMed1996

Field tolerance to fungal pathogens of Brassica napus constitutively expressing a chimeric chitinase gene.

Constitutive overexpression of a protein involved in plant defense mechanisms to disease is one of the strategies proposed to increase plant tolerance to fungal pathogens. A hybrid endochitinase gene under a constitutive promoter was introduced by Agrobacterium-mediated transformation into a winter-type oilseed rape (Brassica napus var. oleifera) inbred line. Progeny from transformed plants was challenged using three different fungal pathogens (Cylindrosporium concentricum, Phoma lingam, Sclerotinia sclerotiorum) in field trials at two different geographical locations. These plants exhibited an increased tolerance to disease as compared with the nontransgenic parental plants.

Ascomycota↗
PubMed1996

Localization of neurotrophins and their high-affinity receptors during human enteric nervous system development.

BACKGROUND & AIMS: Interactions of neurotrophins with the appropriate trk receptors result in growth and maturational alterations in nervous system cells during development. The aim of this study was to examine whether similar interactions could be involved in human enteric nervous system (ENS) survival or differentiation as well. METHODS: Immunocytochemical detection of TrkA, TrkB, and TrkC, as well as the ligands neurotrophin 3 (NT-3) and brain-derived neurotrophic factor (BDNF), was accomplished on normal human fetal and postnatal intestine. RESULTS: Neither neurotrophins nor their receptors were identified in immature postmigrational ENS progenitors at 7 weeks' fetal developmental age; however, TrkC and TrkA were specifically localized to developing ENS cells after 19 developmental weeks. From infancy through adulthood, TrkA and TrkB immunoreactivities were localized to both enteric ganglion cells and glia, whereas TrkC was localized exclusively to enteric ganglion cells. In postnatal intestine, BDNF immunoreactivity was primarily localized to enteric ganglion cells, with NT-3 localized to enteric plexuses, intermuscular basal lamina, and along or between circular and longitudinal smooth muscle cells. CONCLUSIONS: These data indicate that neurotrophic influences may be involved in ENS development and survival, with potential importance in functional differentiation disorders of the intestinal ENS.

Adult↗
PubMed1996

Monoclonal antibodies against human immunodeficiency virus type 1 integrase: epitope mapping and differential effects on integrase activities in vitro.

Human immunodeficiency virus type 1 (HIV-1) integrase (IN) catalyzes the integration of viral DNA into the host chromosome, an essential step in retroviral replication. As a tool to study the structure and function of this enzyme, monoclonal antibodies (MAbs) against HIV-1 IN were produced. Epitope mapping demonstrated that the 17 MAbs obtained could be divided into seven different groups, and the selection of MAbs representing these groups were tested for their effect on in vitro activities of IN. Four groups of MAbs recognized epitopes within the region of amino acids (aa) 1 to 16, 17 to 38, or 42 to 55 in and around the conserved HHCC motif near the N terminus of IN. MAbs binding to these epitopes inhibited end processing and DNA joining and either stimulated or had little effect on disintegration and reintegration activities of IN. Two MAbs binding to epitopes within the region of aa 56 to 102 in the central core or aa 186 to 250 in the C-terminal half of the protein showed only minor effects on the in vitro activities of IN. Three Mabs which recognized on epitope within the region of aa262 to 271 of HIV-1 IN cross-reacted with HIV-2 IN. MAbs binding to this epitope clearly inhibited end processing and DNA joining and stimulated or had little effect on disintegration. In contrast to the N-terminal-specific MAbs, these C-terminal-specific MAbs abolished reintegration activity of IN.

Animals↗
PubMed1996

A developmental model of neuroblastoma: differentiating stroma-poor tumors' progress along an extra-adrenal chromaffin lineage.

The prognosis of children with neuroblastoma (NB) is dependent upon the patient's age at diagnosis, the location of the primary tumor, and histologic tumor cell differentiation. These characteristics, as well as the presumption that NB results from clonal expansion of primitive cells involved in sympathetic nervous system (SNS) development, predict that a model of tumorigenesis based upon normal fetal SNS histogenesis might indicate tumor progenitor status and define biologic and clinical behavior. Immunohistochemistry and in situ hybridization were used to examine a panel of marker gene products predicted or shown to be expressed during SNS development in the normal human fetal SNS from 8 to 24 weeks' gestational age. A similar analysis was performed in a selection of clinical NB tumors, and the results were compared. In a subset of differentiating, often extra-adrenal NB tumors in patients who frequently had a favorable outcome; advancing morphologic tumor cell differentiation spatially paralleled an advancing fetal extra-adrenal chromaffin marker gene expression phenotype (ie, increasing TrkA, TrkC, TH, IGF-2, and neuron-specific enolase expression but a lack of phenylethanolamine N-methyltransferase expression). In these tumors, expression of gene products associated with normal fetal sympathetic ganglionic differentiation (ie, Bcl-2, HNK-1, and neuropeptide Y) was lost with morphologic tumor cell differentiation. In contrast, undifferentiated tumors, the majority of which were high stage, adrenal in origin, and prognostically unfavorable, displayed marker expression characteristics mirroring that of an early fetal ganglionic lineage. Thus, we show that morphologic differentiation in stroma-poor NB tumors, long held as an important prognostic feature in tumor grading systems, often corresponds to an extra-adrenal chromaffin rather than a ganglion cell or adrenal medullary chromaffin phenotype. Understanding the biology of extra-adrenal chromaffin tissues may provide an explanation for the clinically less aggressive nature of differentiating NB tumors and suggest potential mechanisms for spontaneous regression and/or treatment response.

Biomarkers, Tumor↗
PubMed1995

Characterization of the DNA-binding activity of HIV-1 integrase using a filter binding assay.

Based on the selective binding of proteins and DNA to distinct filter materials a double-layered dot blot radio assay was developed to evaluate the binding of DNA to HIV-1 integrase. In this assay the DNA-binding was found to be independent of Mn2+ concentration, inhibited by concentrations of Mg2+ above 5 mM, abolished by zinc chelation and inhibited by monoclonal antibodies reacting with either the N-terminal or C-terminal regions of integrase. Atomic absorption spectroscopy revealed the molar ratio between integrase and zinc to be close to 1. It is concluded that both the N-terminal and the C-terminal regions of integrase are involved in DNA-binding and that the reported double-layered dot blot radio assay is well suited for further characterization of the integrase.

Base Sequence↗
PubMed1995

A mechanochemical model for adult dermal wound contraction and the permanence of the contracted tissue displacement profile.

The healing of adult mammalian skin wounds involves a complex sequence of spatially and temporally coordinated processes. Wound contraction, by reducing the size of the injury, is an intrinsic component of full-thickness excisional dermal wound healing. The underlying biomechanics of wound contraction, however, are not fully understood, and little is known about the pathogenesis of severe medical conditions known as fibrocontractive diseases. The aim of this work is to investigate a deterministic mathematical model in order to obtain insight into the mechanistic relationships between wound contraction and associated normal and pathological healing processes. The model describes the essential roles of fibroblast and myofibroblast cells, a chemical growth factor and the extracellular matrix which includes type I collagen. The model results are qualitatively consistent with the biology of fibroplasia and wound contraction. It is shown that a contracted state evolves during a (long) transient phase of healing known as "proliferation", while collagen kinetics are fundamental to the considerably longer "remodelling" phase. Some quantitative results, notably on the evolution of wound contraction, compare favourably with experimental data. Application of the model to adult human dermal wound healing in vivo, with a greater understanding of the underlying biological mechanisms involved, may suggest strategies for controlling contraction and fibrocontractive diseases.

Adult↗
PubMed1995

Cellular death in neuroblastoma: in situ correlation of apoptosis and bcl-2 expression.

Apoptosis is the selective physiologic deletion of cells that are no longer required. Over-expression of the bcl-2 proto-oncogene extends survival of neurons otherwise destined for apoptosis. The unique capacity of neuroblastoma (NB) to undergo spontaneous regression and the prognostic dichotomy of children with this malignancy led us to evaluate bcl-2 expression and apoptosis in NB. An in situ DNA nick-labeling technique to detect apoptotic cells, as well as immunohistochemistry and morphology, were utilized in a selection of NB tumor specimens and in the human fetal sympathetic nervous system. bcl-2 expression was present in all 28 NB tumors examined and in sympathetic ganglia of the human fetus. Measurement of overall bcl-2 expression and of extent of apoptosis correlated with favorable prognosis. In low-stage tumors, bcl-2 expression was most intense in poorly differentiated tumor cells adjacent to fibrovascular stroma. Cells distant from the stroma exhibited increasing degrees of chromaffin differentiation, with apoptosis most evident in bcl-2-negative neuroblasts adjacent to well-differentiated NB cells. The spatial distribution of bcl-2 expression, apoptosis and chromaffin differentiation in favorable-prognosis NB may provide insight into mechanisms of persistent tumor existence or regression.

Apoptosis↗
PubMed1995

Self-cloning in filamentous fungi: application to the construction of endothiapepsin overproducers in Cryphonectria parasitica.

The filamentous ascomycete fungus Cryphonectria parasitica naturally secretes endothiapepsin, an aspartic proteinase. It is cultured on a commercial scale as a source of the milk-clotting enzyme for cheese making. Our objective was to increase enzyme production of an industrial C. parasitica strain by a new technique of self-cloning; it consisted in the screening for transformants producing higher levels of endothiapepsin and having integrated only the DNA fragment of interest. Such genetically improved strains that are devoid of any foreign genes should be more readily acceptable for the production of food-grade enzymes.

Acetates↗
PubMed1995

Rehbein's anterior resection in Hirschsprung's disease, using a circular stapler.

The results of 30 patients with Hirschsprung's disease, operated by Rehbein's anterior resection, have been evaluated. In 26 children the anastomosis was constructed with a circular stapler (Ethicon Proximate ILS) and in 4 it was handsutured. When a stapler was used, technical problems in 4, with a defect in the rings of bowel after firing the instrument, necessitated reinforcing sutures. The level of the anastomosis was significantly lower in the children in which a stapler was used. Eight children were operated by dorsal myectomy (DRM) prior to and 4 after anterior resection. The children with DRM prior to anterior resection had a significantly lower requirement for postoperative dilations. Early postoperative complications included 3.3% mortality, 6.7% enterocolitis, 3.3% anastomotic insufficiency, 3.3% early ileus and 10.0% wound infection. Three patients (10.0%) were operated for postoperative anastomotic stricture, one requiring anastomotic revision and two requiring DRM. At follow-up two children (7.4%) reported constipation with regular requirement for enemas and two (7.4%) reported daily encopresis. Twenty-three patients had 1-5 bowel movements per day and 4 patients had more than 5. In our experience the use of a circular stapler makes it possible to perform a lower anastomosis. We believe that this technique gives a wider and more elastic anastomosis and is technically less difficult to handle than a handsutured anastomosis.

Anastomosis, Surgical↗
PubMed1995

Neurological dysfunction above cele level in children with spina bifida cystica: a prospective study to three years.

The aim of this study was to characterize the neurological dysfunction above the cele level in children with spina bifida cystica. 22 neonates were investigated prospectively to a median age of three years. Before primary closure of the spinal malformation and at three and 18 months of age, MRI and inspection of vocal cord function were performed. The children were also assessed by a physical therapist at 12 and 24 months, 19 children had a Chiari malformation, 18 children developed neurological dysfunction above the cele level. Children with signs of isolated motor impairment stabilized or improved during the second year. Six children developed severe functional impairment of respiration, feeding and motor performance within the first three months of life. Severe neurological signs/symptoms were associated with myeloschisis, clinical signs of a tethered cord and recurrent periods of shunt dysfunction.

Child, Preschool↗
PubMed1995

Association of neurotrophin receptor expression and differentiation in human neuroblastoma.

Interactions of the trk family of tyrosine kinase receptors with neurotrophins result in growth and maturational changes in neuronal cells. The continued progression, maturation, or regression of neuroblastoma, an embryonal, sympathetic nervous system-derived tumor of infants and children, might be governed by neurotrophic influences. Immunocytochemistry was utilized to evaluate TrkA, TrkB, and TrkC protein expression at the cellular level in the developing human fetal sympathetic nervous system and in a selection of neuroblastoma tumor specimens. TrkA and TrkC expression was identified in sympathetic ganglia and within the adrenal medulla, with intense TrkB expression restricted to paraganglia, of the normal developing human sympathetic nervous system. In neuroblastoma, pp140trkA expression correlated positively with favorable tumor stage (P = 0.0027) and favorable outcome (P = 0.026). No statistically significant correlation of TrkC expression with outcome was evident; however, both TrkA and TrkC expression was most apparent in tumor cells of increased differentiation. TrkB expression was primarily localized to cells within the fibrovascular tumor stroma. A model of neurotrophin receptor expression and neurotrophin reactivity with differentiation is proposed. The existence and spatial distribution of neurotrophin receptors in neuroblastoma lend supportive evidence that neurotrophic influences may be involved in tumor persistence or regression.

Adrenal Medulla↗
PubMed1994

[Methods for measurement of wound extent].

Healing is a biologically complicated process, which is difficult to measure objectively. Several products and pharmaceuticals have been applied to the treatment of both acute and chronic wounds. There are, however, only few well-documented studies of the effect and many recommendations are based on casuistries, undocumented studies or in vitro studies. One of the most prominent problems has been the lack of exact measurements. This article describes the available clinical measurement parameters and discusses their strengths and weaknesses. The following methods of measurement are described: Wound surface area (WSA), wound area (WA), and volume (VOL). A stratification of wounds before measuring is suggested depending on aetiology and form (volume or surface wounds). The most sensitive measure for assessment of wound healing is recommended. From a clinical point of view the transition from a volume to surface wound is not distinct, and therefore WA is recommended as the most relevant measurement during wound healing.

Body Surface Area↗
PubMed1994

Activity of cyclosporins as resistance modifiers in primary cultures of human haematological and solid tumours.

The semiautomated fluorimetric microculture cytotoxicity assay (FMCA) was used for evaluation of the ability of cyclosporin A (CsA) and its novel non-immunosuppressive derivative SDZ PSC 833 (PSC) to modify the response to doxorubicin or vincristine in vitro in different haematological and solid human tumour types. Primary cultures of 322 tumour samples were analysed. Both cyclosporins showed resistance-modifying activity in all haematological tumours tested, and in solid tumours activity was observed in ovarian carcinoma and childhood tumours. Little or no effect was found in the remaining tumour types, including breast, renal and adrenal cortical carcinomas and adult sarcomas. In most of the responsive cases the interaction between the modifier and the cytotoxic drug was synergistic. There was a tendency to higher activity in samples from previously treated patients, and an inverse relationship between degree of cytotoxic drug resistance and resistance-modifying activity was noted. No difference in potency between CsA and PSC could be discerned. The results indicate differential in vitro resistance-modifying activity of the cyclosporins depending on tumour type. The results also suggest that treatment with resistance modifiers should be considered also for primary therapy of drug-sensitive tumours. Drug resistance assays such as the FMCA may become useful in preclinical evaluation of resistance modifiers.

Antineoplastic Agents↗
PubMed1992

N-myc gene amplification in neuroblastoma: a clinical approach using ultrasound guided cutting needle biopsies collected at diagnosis.

N-myc gene amplification was studied in a consecutive series of neuroblastomas and ganglioneuromas, representing all of such tumours diagnosed in Sweden over a 4-year period. Both frozen and formalin fixed specimens were used for Southern blot analysis. Thirty-seven of 46 neuroblastomas and 7 of 9 ganglioneuromas were analyzed. Seven neuroblastomas and none of the ganglioneuromas showed N-myc gene amplification. All children with amplified tumours, including three infants, had advanced disease at diagnosis and aggressive course of disease. However, follow-up time was short for the two cases still alive. The use of an ultrasound guided cutting needle biopsy technique for obtaining the required tissue at diagnosis was evaluated in some cases. This technique appeared to be safe and clinically useful since early prognostic information was obtained. Using an imprint from the needle biopsy, the representativity could be confirmed. Ultrasound guided cutting needle biopsies can thus be used routinely to obtain N-myc gene amplification data prior to initiation of therapy in neuroblastoma.

Biopsy, Needle↗
PubMed1992

Sacrococcygeal teratoma in Sweden: a 10-year national retrospective study.

Thirty-two children with sacrococcygeal teratoma have been treated during the last 10 years (1980 to 1989) in Sweden. A retrospective study was performed in four departments of pediatric surgery that treat sacrococcygeal teratomas in children from the whole of Sweden. Prenatal and perinatal histories were reviewed together with interval to diagnosis, Altman classification, histology, and serum alpha-fetoprotein. Details of surgical management +/- adjuvant chemotherapy and outcome of patients were also documented. In 8 patients the teratoma was diagnosed prenatally by ultrasonography and there was one postoperative death in this group. Multiagent chemotherapy was used in all but one of 11 patients with malignant teratomas (in 8 of them a cisplatin, bleomycin, vinblastine combination). Only one patient with a malignant tumor treated by single-agent chemotherapy died, 8 others were still alive and tumor-free after 1 to 9 years (mean time, 5.4 years). Two patients developed late relapses and were treated by surgical resection. Metastases occurred in five of the 11 malignant tumors, one at presentation and in four patients 10 to 29 months following surgery. All relapses had distant metastases as well as local disease. Serum alpha-fetoprotein was used in monitoring some of these patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Multiple intestinal duplications in a child with thoracic myelomeningocele and hydrocephalus.

An infant with thoracic spina bifida, myelomeningocele and hydrocephalus was found to have intrathoracic gastric duplication and noncontiguous tubular duplication along two-thirds of the small bowel. The myelomeningocele was closed and the hydrocephalus relieved with a shunt. The intrathoracic duplication was excised in toto and the intra-abdominal malformation successfully treated by stripping the entire mucosal tube from within the duplication.

Abnormalities, Multiple↗