Biomedical subjects

Hans Jørgen G Gundersen

Publications and source records attributed to Hans Jørgen G Gundersen.

8 recordsLinked to original sources

PubMed2006

The postnatal development of cerebellar Purkinje cells in the Göttingen minipig estimated with a new stereological sampling technique--the vertical bar fractionator.

The postnatal development of total number and perikaryon volume of cerebellar Purkinje cells was estimated in the Göttingen minipig cerebellar cortex using a new stereological approach, the vertical bar fractionator. Data were obtained from the brains of five neonate and five adult female Göttingen minipigs. The total number of Purkinje cells ranged from 1.83 x 10(6) in the neonate to 2.82 x 10(6) in the adult Göttingen minipig. The number-weighted mean perikaryon volume of Purkinje cells increased concurrently from around 6,800 microm(3) in the neonate to 17,600 microm(3) in the adult. The study demonstrates that a pronounced postnatal neurogenesis in Purkinje cell number and perikaryon volume is part of the growth and development of the cerebellum in the Göttingen minipig. The Purkinje cells of the Göttingen minipig were found to be substantially large compared with human and represents the largest cells described hitherto from mammalian cerebella. The vertical fractionator is a new sampling technique, which allows the combination of a fractionator design on vertical bar sections excluding exhaustive sampling and bias from artificial edges. By design, the sections are perfect stereological vertical sections and provide the basis for unbiased estimates of total number of structural entities in the brain, including surface area, fibre length and particle volume.

Animals↗

PubMed2005

Assessment of in vivo MR imaging compared to physical sections in vitro--a quantitative study of brain volumes using stereology.

The object of the present study was to compare stereological estimates of brain volumes obtained in vivo by magnetic resonance imaging (MRI) to corresponding volumes from physical sections in vitro. Brains of ten domestic pigs were imaged using a 3-T scanner. The volumes of different brain compartments were obtained from MR images by two observers and from physical sections using the Cavalieri estimator in combination with point counting. Paired t tests revealed no significant differences between the two methods for any of the five compartments considered, except for the basal gray compartment. However, although intraobserver difference of MRI estimates was acceptable, the interobserver difference was not. A statistical highly significant difference of 11-41% was observed between observers for volume estimates of all compartments considered. The study demonstrates that quantitative MRI is susceptible to observer dependent interpretation of images.

Algorithms↗

PubMed2005

Design-based stereological analysis of the lung parenchymal architecture and alveolar type II cells in surfactant protein A and D double deficient mice.

Alveolar epithelial type II cells synthesize and secrete surfactant. The surfactant-associated proteins A and D (SP-A and SP-D), members of the collectin protein family, participate in pulmonary immune defense, modulation of inflammation, and surfactant metabolism. Both proteins are known to have overlapping as well as distinct functions. The present study provides a design-based stereological analysis of adult mice deficient in both SP-A and SP-D (A(-)D(-)) with special emphasis on parameters characterizing alveolar architecture and surfactant-producing type II cells. Compared to wild-type, A(-)D(-) mice have fewer and larger alveoli, an increase in the number and size of type II cells, as well as more numerous and larger alveolar macrophages. More surfactant-storing lamellar bodies are seen in type II cells, leading to a threefold increase in the total volume of lamellar bodies per lung, but the mean volume of a single lamellar body remains constant. These results demonstrate that chronic deficiency of SP-A and SP-D in mice leads to parenchymal remodeling, type II cell hyperplasia and hypertrophy, and disturbed intracellular surfactant metabolism. The design-based stereological approach presented here provides a framework for the quantitative lung structure analysis in gene-manipulated mice as well as in human lung disease.

Animals↗

PubMed2004

Detection of circulating tumor lysate-reactive CD4+ T cells in melanoma patients.

PURPOSE: We wanted to study whether an allogeneic melanoma lysate would be a feasible stimulatory antigen source for detection of a peripheral CD4+ T-cell immune response in patients with medically untreated malignant melanoma. The lysate was produced from a melanoma cell line (FM3.29) which expresses high amounts of melanoma antigens. METHODS: Fresh peripheral blood was incubated with and without lysate for 6 h in the presence of anti-CD28/anti-CD49d MoAb (for costimulation). After flow cytometric estimation of the frequency of CD69+/IFN-gamma+ cells in the CD4+ population, the response to lysate was calculated as the difference between the number of activated IFN-gamma-producing CD4+ cells in the lysate-stimulated and the nonstimulated sample. RESULTS: An immune response to lysate was observed in blood samples from 11 of 15 patients (73%) with metastatic melanoma. A weak response was found in 1 of 4 patients radically operated for localized disease, whereas no responders were seen among 7 healthy donors. The fraction of circulating lysate-activated T cells ranged from 0.0037% to 0.080% of the CD4+ population. A negative result of the assay was found occasionally, especially in donors with high background levels of spontaneous IFN-gamma production, indicating an inhibitory effect of the lysate. CONCLUSIONS: This method for detection of a peripheral T-cell immune response in melanoma patients has several advantages for clinical use. The tumor lysate preparations may contain large numbers of stimulating antigens (known, as well as unknown) and are easily prepared and handled. Potentially, the assay might be useful as a diagnostic tool, a marker of residual or recurrent disease, a prognostic factor, or a predictor or monitor of the effect of antineoplastic therapy including immune-modulating therapy.

Adult↗

PubMed2003

Aging of the human cerebellum: a stereological study.

Cerebella from 19 normal Caucasian males, ages 19-84 years, were studied using stereological methods. Cerebellum was divided into four different regions: the anterior and posterior lobe, the vermis, and the flocculonodular lobe. Total volume of the cerebellar cortex and white matter, cerebellar surface area, total Purkinje and granule cell number, and the distribution of the volumes of the Purkinje cells and their nuclei were estimated in all four regions. The global white matter was reduced by 26% with age; the mean volume of the Purkinje cell body was decreased by 33% with no decrease in the volume of the Purkinje cell nuclei. A tendency towards a 16% total cerebellar volume loss was seen without a concomitant neuron loss. No global Purkinje or granule cell loss was detected with age, total Purkinje cell number being 28 x 10(6) (coefficient of variation, CV = 0.16) and total granule cell number 109 x 10(9) (CV = 0.17). However, a significant change was observed with age in the anterior lobe, where a selective 40% loss of both Purkinje and granule cells was found. Furthermore, a 30% loss of volume, mostly due to a cortical volume loss, was recorded in the anterior lobe, which is predominantly involved in motor control.

Adult↗

PubMed2003

The number of alveoli in the human lung.

The number of alveoli is a key structural determinant of lung architecture. A design-based stereologic approach was used for the direct and unbiased estimation of alveolar number in the human lung. The principle is based on two-dimensional topology in three-dimensional space and is free of assumptions on the shape, size, or spatial orientation of alveoli. Alveolar number is estimated by counting their openings at the level of the free septal edges, where they form a two-dimensional network. Mathematically, the Euler number of this network is estimated using physical disectors at a light microscopic level. In six adult human lungs, the mean alveolar number was 480 million (range: 274-790 million; coefficient of variation: 37%). Alveolar number was closely related to total lung volume, with larger lungs having considerably more alveoli. The mean size of a single alveolus was rather constant with 4.2 x 10(6) microm3 (range: 3.3-4.8 x 10(6) microm3; coefficient of variation: 10%), irrespective of the lung size. One cubic millimeter lung parenchyma would then contain around 170 alveoli. The method proved to be very efficient and easy to apply in practice. Future applications will show this approach to be an important addition to design-based stereologic methods for the quantitative analysis of lung structure.

Culture Techniques↗

PubMed2003

Autogenous bone graft and ePTFE membrane in the treatment of peri-implantitis. II. Stereologic and histologic observations in cynomolgus monkeys.

The purpose of the present study was to evaluate the effect of autogenous bone graft particles and expanded polytetrafluoroethylene (ePTFE) membrane in the treatment of peri-implantitis with stereologic and histologic methods. Clinical and radiographic findings are reported elsewhere. Experimental peri-implantitis with a bone loss of 4-6 mm was established during 14-22 months around 64 implants with a titanium plasma-sprayed (TPS) surface in eight cynomolgus monkeys (Macaca fascicularis). The defects were treated with autogenous bone+membrane (B+M), autogenous bone (B), membrane (M), or a conventional flap procedure (control) (C). The animals were killed 6 months after surgery. Healthy peri-implant tissue was established irrespective of the applied treatment procedure. However, the amount of bone (autogenous bone graft particles and regenerated bone) and re-osseointegration were significantly higher in defects treated with B+M as compared with the three other treatment modalities. A mean bone-to-implant contact of 45% was estimated within defects treated with B+M. The corresponding values for the B, M, and C groups were 22, 21, and 14%. The present study therefore demonstrates that autogenous bone graft particles covered by an ePTFE membrane is a useful surgical treatment procedure of experimental peri-implantitis around implants with a TPS surface in cynomolgus monkeys. Obviously, there is a background for long-term evaluation in humans.

Alveolar Bone Loss↗

PubMedDate not supplied

Aging and the human neocortex.

Neurostereology has been applied to quantitative anatomical study of the human brain. Such studies have included the total neocortical number of neurons and glial cells, the estimated size distribution of neocortical neurons, the total myelinated fiber length in the brain white matter, the total number of synapses in the neocortex, and the effect of normal aging on these structural elements. The difference in total number of neurons was found to be less than 10% over the age range from 20 to 90 years, while the glial cell number in six elderly individuals, mean age 89.2 years, showed an average number of 36 billion glial cells, which was not statistically significantly different from the 39 billion glial cells in the neocortex of six young individuals with a mean age of 26.2 years. The total myelinated fiber length varied from 150,000 to 180,000 km in young individuals and showed a large reduction as a function of age. The total number of synapses in the human neocortex is approximately 0.15 x 10(15) (0.15 quadrillion). Although the effect of aging is seen in all estimated structural elements, the effect of sex is actually higher. The functional relevance of these differences in neuron numbers in both age and gender is not known.

Adult↗