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Biomedical subjects

P H Burri

Publications and source records attributed to P H Burri.

At least 19 recordsLinked to original sources
PubMed1995

Immunostaining of a heterodimeric dermatan sulphate proteoglycan is correlated with smooth muscles and some basement membranes.

A heterodimeric 760-kDa dermatan sulphate proteoglycan tentatively named PG-760 was characterized as a product of keratinocytes, endothelial cells, and fibroblasts. The two core proteins of 460 kDa and 300 kDa are linked by disulphide bridges, and both carry one or only very few dermatan sulphate chains. Different antisera against PG-760 were used in the present study to investigate the distribution in selected murine tissues by light and electron microscopy. PG-760 immunostaining was observed in cornea (epithelium including basement membrane, stroma, and Descemet's membrane), skin, mucosa of the small intestine, Engelbreth-Holm-Swarm (EHS)-tumour (matrix and cells), and the smooth muscle layers of uterus, small intestine, and blood vessels. No staining was observed in capillaries, striated muscles, and liver parenchyma including the central vein. The expression of PG-760 in EHS-tumour was also demonstrated after extraction with 4 M guanidine and partial purification by diethylaminoethyl (DEAE)-chromatography. We conclude that this novel proteoglycan exhibits a unique tissue distribution being a constituent of some but not all basement membranes, of some other extracellular matrices, and additionally, of all investigated smooth muscle layers.

Animals↗
PubMed1995

Protein deficiency and the growing rat lung. I. Nutritional findings and related lung volumes.

We investigated the consequences of early malnutrition on milk production by dams and on body weight and structural lung growth of young rats using two models of protein restriction. Dams of the early restriction group were fed an 8% casein diet starting at parturition. Those of the delayed restriction group received a 12% casein diet from lactation d 8-14 and thereafter the 8% diet. After weaning, early restriction and delayed restriction group rats were maintained on low protein until d 49, then refed the control diet (18% casein) up to d 126. Milk was analyzed on d 12. Animals were killed at d 21, 49, and 126 for lung fixation in situ. In this report, we show that protein restriction lowered milk yield to 38% of normal. Milk lipid per gram of dry weight tended to be increased, whereas lactose and protein were significantly decreased. Pups from protein-restricted dams grew less and had lower lung volumes, effects being more serious at d 49. However, specific lung volumes (in milliliters per 100 g body weight) were constantly increased. This means that lung was either less affected than body mass or overdistended due to less connective tissue. After refeeding, both groups showed a remarkable catch-up in growth with restoration of the normal allometric relationship between lung volume and body weight. Thus, even after an early onset of protein restriction to total body, the lung is still capable to substantially recover from growth retardation.

Animals↗
PubMed1995

Protein deficiency and the growing rat lung. II. Morphometric analysis and morphology.

Effects of protein deficiency during the whole period of postnatal development and intensive growth were studied in the rat lung parenchyma. Dams received a low protein diet as follows: early restriction, 8% casein diet from parturition, and delayed restriction, 12% then 8% casein diet from lactation d 8. After weaning (d 21), early restriction and delayed restriction group rats were maintained on the 8% casein diet until d 49, wherefore they were returned to normal food (18% casein) for 11 wk. Lungs were processed for light and electron microscopic morphometry on d 21, 49, and 126. The diffusion capacity of the lung for O2 (DLO2) was also determined from the morphologic parameters. Volume and surface densities of the parenchymal components of malnourished rats did not consistently differ from controls. Because of lower lung volumes, absolute values, including DLO2, were all significantly decreased. Further, although lung volume growth was less impaired than body growth and thus deviated from the normal allometric relationship, most morphometric parameters paralleled body weight changes. Visually, we detected minor morphologic alterations at d 21 and 49, not necessarily reflected by morphometric data. But, importantly, lung parenchyma appeared mature at weaning despite the growth retardation. Normal refeeding resulted in a striking regrowth of the lung parenchyma. Although early restriction rats did not fully catch up in lung volume, most parenchymal parameters and DLO2 were largely restored in both refed groups.

Animals↗
PubMed1993

Morphometric analysis of fetal rat lung development.

Applying the zone concept described previously, we quantitatively analyzed fetal rat lung development. The zone concept allowed us to coherently define reference spaces in the developing lung, a prerequisite for morphometric analysis. The peripheral zone I corresponds to a zone of growth of yet undifferentiated tissues; zone II arises from zone I and represents a region of structural and cellular differentiation; zones III and IV comprise the conducting airways and vessels. Lungs of fetal rats aged 17-23 days and 20 hours postnatal were fixed with OsO4 and glutaraldehyde and processed for light and electron microscopic morphometry implemented by point and intersection counting. Fetal lung volume grew in proportion to body weight. Zone II being the largest compartment, its volume changes largely determined lung growth rates. Zone II increased in mass owing to differentiation processes at the interface to zone I where the proximal portions of zone I were continuously shifted into zone II by differentiation. New tissue was generated within zone I. Due to these combined processes zone I changed little in volume until it disappeared at the end of the canalicular stage. The presence in the pseudoglandular stage of half of the parenchymal epithelial mass available around birth indicated that parenchymal development started earlier than assumed so far. While the endothelial surface increased most at birth, the epithelial surface grew by more than 600% at day 21, reflecting the onset of canalisation. The study confirmed the usefulness of the zone concept for morphometry and provided some new insights into lung development.

Animals↗
PubMed1993

Evidence for intussusceptive capillary growth in the chicken chorio-allantoic membrane (CAM).

The aim of our investigations was to test whether the chicken chorio-allantoic membrane (CAM) could be an adequate in vivo model for a new mode of capillary growth, originally described in the rat lung and termed intussusceptive microvascular growth. According to that concept the capillary system does not grow by sprouting of vessels, but expands by insertion of transcapillary tissue pillars or posts which form new intercapillary meshes. In the present study, we observed slender transcapillary tissue pillars with diameters around 1 microns in the CAM by in vivo microscopy, and analyzed their ultrastructure by transmission electron microscopic investigation of serial sections. The pillars corresponded in size to those previously described in rat lung microvasculature. On day 7, the pillar core contained endothelial-, endothelial-like cells and collagen fibers, and on day 12 additionally chorionic epithelial cells. As a hypothesis we propose that slender cytoplasmic extensions of endothelial cells, heavily interdigitated in the post area and often projecting into the vascular lumen, could initiate the first step of pillar formation, i.e., interconnect opposite capillary walls. During both stages of development endothelial-like cells were observed in close relationship with the pillars. These cells seem to be relevant for tissue post completion and growth, as they were found to invade the core of the pillars. From the localization of the interendothelial junctions in the post region, a certain similarity to the concept proposed for the lung can be found. The observations confirm that the CAM is a very suitable material for the in vivo investigation of intussusceptive capillary growth.

Allantois↗
PubMed1992

Structural analysis of fetal rat lung development.

The primary aim of this morphological investigation was to elaborate a concept allowing us to coherently define reference spaces for morphometric analysis of fetal lung development. Beyond this quantitative goal, morphological analysis of cell types, definition of compartments, and reflection about the prospective fate of their constituents provided per se new insights into the developmental processes. Lungs of rat fetuses aged 17-23 days and newborns aged 20 hours were fixed with an osmium tetroxide and glutaraldehyde mixture and their volume determined. Left lungs were embedded in Epon and investigated by light and electron microscopy. The right lung of one animal per group was embedded in methacrylate and step sections obtained to precisely locate the airways within the mesenchyme. The various cell types, their topographical relationships, and their morphological alterations with ongoing development were analyzed with regard to their prospective potentials of differentiation. The developing lung could be partitioned into four zones further subdivided into defined compartments. Zone I forms a superficial mantle around the lobes and the future acini. Consisting of primitive mesenchymal cells, it represents a zone of growth which disappears with the onset of the saccular stage. Zone II is mainly a zone of differentiation. Its interstitium stains intensely due to a dense population of dark cells. Up to gestational day 19, zone II contains future conductive airways with their vessels. After day 21, it comprises the whole prospective gas exchange region. Zones III and IV contain the elements of the airway tree and vascular system, zone IV corresponding to the most proximal generations with an adventitial layer. For all differentiation processes, a centrifugal directionality is manifested.

Animals↗
PubMed1992

Intussusceptive microvascular growth, a new mechanism of capillary network formation.

Growth by intussusception is defined as growth by deposition of new particles or pieces of formative material among those already embodied in a tissue or structure. In the context of capillary growth the term stands for the extension of the capillary system by the insertion of new capillary meshes within the existing network. New meshes arise as slender transcapillary tissue pillars. These are formed initially by a circumscribed fusion of opposite endothelial leaflets. Following reorganization of the junctional complexes, the pillar is invaded by interstitial tissue. This means that for the formation of new capillaries no sprouting of endothelial cords or tubules is required. The mechanism is described in the growing lung, but may occur in other tissues too. There may be a chance for in vivo observation of the process in the capillaries of the chorio-allantoic membrane of the chicken.

Aging↗
PubMed1992

Overexpression of Mos, Ras, Src, and Fos inhibits mouse mammary epithelial cell differentiation.

Mammary epithelial cells terminally differentiate in response to lactogenic hormones. We present evidence that oncoprotein overexpression is incompatible with this hormone-inducible differentiation and results in striking cellular morphological changes. In mammary epithelial cells in culture, lactogenic hormones (glucocorticoid and prolactin) activated a transfected beta-casein promoter and endogenous beta-casein gene expression. This response to lactogenic hormone treatment was paralleled by a decrease in cellular AP-1 DNA-binding activity. Expression of the mos, ras, or src (but not myc) oncogene blocked the activation of the beta-casein promoter induced by the lactogenic hormones and was associated with the maintenance of high levels of AP-1. Mos expression also increased c-fos and c-jun mRNA levels. Overexpression of Fos and Jun from transiently transfected constructs resulted in a functional inhibition of the glucocorticoid receptor in these mouse mammary epithelial cells. This finding clearly suggests that glucocorticoid receptor inhibition arising from oncogene expression will contribute to the block in hormonally induced mammary epithelial cell differentiation. Expression of Src resulted in the loss of the normal organization and morphological phenotype of mammary epithelial cells in the epithelial/fibroblastic line IM-2. Activation of a conditional c-fos/estrogen receptor gene encoding an estrogen-dependent Fos/estrogen receptor fusion protein also morphologically transformed mammary epithelial cells and inhibited initiation of mammary epithelial differentiation-associated expression of the beta-casein and WDNM 1 genes. In response to estrogen treatment, the cells displayed a high level of AP-1 DNA-binding activity. Our results demonstrate that high cellular AP-1 levels contribute to blocking the ability of mammary epithelial cells in culture to respond to lactogenic hormones. This and other studies indicate that the oncogene products Mos, Ras, and Src exert their effects, at least in part, by stimulating cellular Fos and probably cellular Jun activity.

Animals↗
PubMed1992

Intussusceptive microvascular growth: a common alternative to capillary sprouting.

Intussusceptive capillary growth represents a new principle for microvascular growth as described in the lungs of growing rats. According to this concept, the capillary network expands by the formation of slender transcapillary tissue pillars, which give rise to new vascular meshes. The process was first observed in Mercox casts of the lung microvasculature, which revealed the existence of multiple tiny holes with diameters around 1.5 microns. Consecutive transmission electron microscopic investigation of serial sections demonstrated that the holes corresponded to slender tissue pillars (Burri and Tarek, 1990). The corrosion cast technique thus appears to be an adequate screening method for intussusceptive growth. In the present investigation, Mercox casts of various vascular systems, namely, those of the eye, submandibular gland, heart, liver, stomach, small and large intestine, trachea, kidney, uterus and ovary were prepared from rats aged between 4 and 9 weeks in order to screen them for the existence of the typical tiny holes representing tissue pillars. In all organs investigated, these structures were observed in various locations to a variable degree. They were mainly encountered within dilated vascular segments or at triple or quadruple branching points of the circulation. Even in capillary networks with a three-dimensional arrangement could these pillars be detected. Intussusception thus appears to be a principle of growth appertaining to many vascular systems.

Animals↗
PubMed1991

Mammary epithelial differentiation in vitro: minimum requirements for a functional response to hormonal stimulation.

Mammary epithelial differentiation is the culmination of responses to a complex sequence of hormonal stimuli. An in vitro model for this process should retain the basic features of in vivo epithelial differentiation. The IM-2 mouse mammary cell line responds to lactogenic hormone stimulation by synthesizing the milk protein beta-casein. Epithelial and fibroblastic clones derived from IM-2 lack this ability, but cocultures of these clones regain responsiveness to lactogenic hormone stimulation. Studies of the epithelial cell clone 31E under various culture conditions reveal that the role of fibroblastic cells in supporting synthesis and secretion of beta-casein can be supplanted by culture in filter chambers without addition of exogenous extracellular matrix components. Electron microscopic and immunofluorescence studies show that, under these conditions, 31E epithelial cells exhibit the morphology and intercellular organization characteristic of mammary epithelium. Transepithelial electrical resistance measurements indicate that the cells are well polarized. Analysis of glucose metabolism is consistent with this polarization; glucose is utilized from the basal chamber, and lactate is excreted into the basal chamber. Immunoblot analysis demonstrates the vectorial protein secretion expected of polarized mammary epithelium: laminin is secreted into the basal chamber, whereas beta-casein is secreted into the apical chamber in response to lactogenic hormone stimulation from the lower chamber. Thus, the maintenance of a polarized intercellular organization that permits access of the basolateral cell surface to nutrients is sufficient for a pure culture of an established mammary epithelial cell clone to retain differentiated epithelial function in vitro.

Animals↗
PubMed1990

A novel mechanism of capillary growth in the rat pulmonary microcirculation.

Postnatally, the rat lung parenchyma undergoes impressive growth. Within four months of birth, lung volume and alveolar and capillary surface areas increase over 20-fold and capillary volume 35-fold. Investigation of methacrylate casts of the pulmonary microvasculature revealed that, with age, lung capillaries were not only growing in surface and volume but also increasing their network density. We proposed that the capillary bed grows by formation of slender intravascular tissue pillars and termed this type of growth intussusceptive microvascular growth (Caduff et al., Anat. Rec., 216:154-164, 1986). The aim of this investigation was to detect the presence and to analyze the ultrastructure of slender tissue posts (diameter 1-2.5 microns) extending across the capillary lumina in serial electron microscopic sections of rat lung parenchyma (age 44 days). Computer-assisted three-dimensional reconstruction of the capillary lumen confirmed that tissue posts were matching the holes previously observed in casts. Post ultrastructure varied with size from a simple area of interendothelial contact to tissue pillars with a core of interstitial tissue. Based on the changing morphology of the pillars, a hypothesis for their development can be proposed: phase I, creation of a zone of contact between opposite capillary walls (formation of an interendothelial bridge); phase II, reorganization of the intercellular junctions of the endothelium, with central perforation of the capillary layer; phase III, formation of an interstitial post core, with successive invasion by cytoplasmic extensions of myofibroblasts, pericytes, and finally interstitial fibers; and phase IV, growth of the slender pillar to a normal full size capillary mesh. These findings support the new concept of intussusceptive growth of the lung capillary system.

Animals↗
PubMed1987

The postnatal development and growth of the human lung. I. Morphometry.

The lungs of 7 children (age: 26 days to 5 years 4 months) who died from non-respiratory causes were morphometrically investigated by means of light and electron microscopy. For analysis, the set of data was supplemented with results obtained previously on 8 normal adult lungs using similar quantitative techniques (Gehr et al., 1978). The results allowed us to distinguish two phases of postnatal lung development and growth, the first phase lasting from birth to about 18 months and the second phase from then to adulthood. The first phase was characterized by an overproportionate volume increase in the O2-transporting media, air and blood, at the expense of the parenchymal tissue compartment. In the second phase, the volumetric composition of the lung did not change further because there was proportionate growth of all lung compartments. The growth curves for the airspace and capillary surface areas were not biphasic: they increased in direct proportion to lung volume from birth to adulthood, indicating a steady increase in the air-blood interface complexity during the entire growth period. As a consequence of the differences in growth paces between the various structural lung components in early childhood, the morphometric parameters showed large variations in their overall growth rates between birth and adulthood. Thus, the parenchymal tissue components increased by a factor of 15, lung volume and the gas-exchange surface areas between 20 and 25 times (in parallel to body mass), and, finally, the O2-transporting media, air and blood, more than 30 times. The morphometrically determined pulmonary diffusing capacity for O2 (DLO2) scaled with body mass to the power of 1.15, a value significantly different from 1. This relative improvement with age of the gas exchange function per unit body mass is due mainly to an overproportionate growth of the capillary blood compartment.

Adult↗
PubMed1987

The postnatal development and growth of the human lung. II. Morphology.

The morphology of postnatal human lung development and growth has been investigated by light and by scanning and transmission electron microscopy in seven children dying from non-respiratory causes and aged between 26 days and 64 months. The findings are compared with those of adult human lungs and are discussed in relation to the postnatal lung development in other species, particularly rodents. Within the first 1 1/2 postnatal years lung parenchyma undergoes a substantial structural remodeling due to bulk alveolar formation and to the restructuring of septal morphology. At one month alveolar formation appears to be well under way: The human lung is comparable then to a rat lung aged one week. In the parenchyma, numerous short and blunt tissue ridges, so-called secondary septa, subdivide the peripheral airspaces into an increasing number of still very shallow alveoli. The parenchymal septa present during and after alveolization are immature: they contain a double capillary network with a central, highly cellular sheet of connective tissue. The septal maturation sets in a few months after birth and consists of a reduction in the interstitial tissue mass and a complex process of capillary remodeling. Both alveolization and parenchymal maturation progress rapidly: by 6 months the lung has taken a big step towards maturity. By 1 1/2 years most septa show the adult structure where a single capillary network interwoven with connective tissue strands stabilizes the interalveolar wall. After the septal restructuring, lung development is considered complete, and the lung enters a period of normal growth that lasts until adulthood. From our observations we conclude that postnatal human lung development is made of two overlapping stages: (a) the alveolar stage, which starts in late fetal life and lasts to about 1-1 1/2 years, and (b) a stage of microvascular maturation, thought to extend from the first months after birth to the age of 2-3 years.

Adult↗
PubMed1986

Scanning electron microscope study of the developing microvasculature in the postnatal rat lung.

During postnatal growth the parenchymal septa of rat lung undergo an impressive restructuring. While immature septa are thick and contain two capillary layers, mature septa are slender and contain a single microvascular network. Using the Mercox casting technique and scanning electron microscopy, we investigated the mode and the timing of the transformation of the pulmonary capillary bed. During the third postnatal week the parenchymal septa rapidly mature to match adult morphology. Even in adult lungs, however, remnants of the immature status are present: A capillary bilayer is regularly found at the base and the tip of the septa. Our observations support the concept that reduction of intervening tissue, partial fusion of the two capillary networks, and preferential growth lead to the mature vascular arrangement. The fact that true mature interalveolar septa show a denser capillary network than alveolar walls abutting onto pleura, bronchi, or larger vessels is consonant with the fusion theory. Towards the nonparenchyma, the capillary network surrounding every airspace had no counterpart to fuse with. From quantitative data it can be calculated that owing to lung growth, mesh size should increase more than four times between birth and adult age. The adult lung network, however, is denser than the one in young animals. This means that new meshes must be added during growth. We propose that small holes observed in sheet-like regions of the microvasculature enlarge to form new capillary meshes. With this mechanism of in-itself or intussusceptional growth, sprouting of individual capillary segments to increase network size is no longer needed.

Age Factors↗
PubMed1985

Timing of the quantitative recovery in the regenerating rat lung.

Growing rats 23 days of age were subjected to the resection of the upper and middle lobes of the right lung (25% of total lung volume). On postoperative days 1, 4, 6, 9, 12, 18, and 30, the lungs of 5 animals were fixed by intratracheal instillation of glutaraldehyde, their volumes measured by water displacement, and the lung tissue processed for quantitative light (LM) and electron microscopic (EM) investigations. For each group, 3 age-matched sham-operated, and 4 normal rats served as controls. Sham operation consisted in entering the pleural space, and collapsing and ventilating the lungs. In all animals, the following parameters were measured by means of point and intersection counting stereology at either LM or EM-levels: volume densities of lung parenchyma and of its components (airspaces, tissue, capillary blood) and surface densities of airspaces and of capillaries. From these data absolute parameter values were calculated for each lung. The results showed that after bilobectomy the remaining lung re-expanded rapidly first by an overinflation of the airspaces and after Day 4 by an increase in tissue mass and capillary volume. On Days 9 and 12 the operated lungs did not differ quantitatively from control lungs. Later, however, further sequels of the bilobectomy were detected: On Day 18, lobectomy-lungs were smaller than controls, and on Day 30 lungs, the left lung was significantly different in structure from the right lung and from control lungs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

[How useful is the ultrastructural study of the cilia of the respiratory tract in the diagnosis of an immotile cilia syndrome?].

The immotile cilia syndrome (ICS) comprises a range of congenital defects of the ciliary apparatus most probably transmitted by autosomal recessive inheritance. Because cilia occur mainly in the respiratory and genital tract, the clinical symptoms of ICS are most commonly chronic sinusitis, bronchitis, bronchiectasis and male sterility. The syndrome can be associated with a situs inversus and is then called Kartagener's syndrome. We studied the ciliary ultrastructure in airway biopsies of 5 patients suffering from chronic upper and lower respiratory tract infections. With the single exception of one female patient with confirmed ICS diagnosis (Kartagener's syndrome) the etiology of the recurrent infections was unknown. The following ciliary defects were observed: missing dynein arms, radial spoke defects, missing nexin links, microtubular transpositions, compound cilia, supernumerary, absent, or incomplete microtubules, lack of ciliary orientation and various abnormal patterns of microtubular arrangement. In no instance did a patient show only a single anomaly; defects were always combined. Missing dynein arms, radial spoke defects and microtubular transpositions have frequently been described as lesions specific for ICS. Whenever these lesions were found simultaneously in both the respiratory and genital tracts, their genetic origin cannot be doubted. In our confirmed ICS patient the outer dynein arms were not missing but were reduced in number and length in a large number of cilia. The biopsy was, however, obtained from the heavily infected maxillary sinus and it is known that inflammation can lead to a loss of dynein arms. In the light of our investigations and of a review of the published cases of ciliary anomalies, it is concluded that none of the above defects in itself is specific for ICS. They may all occur as secondary lesions or sporadically as varieties in otherwise healthy subjects. It therefore appears questionable whether ICS can be diagnosed from the ciliary ultrastructure of a single airway biopsy. Assessment of ICS cannot be based simply on the ultrastructural demonstration of a particular ciliary defect, but necessitates additional considerations particularly regarding the origin of the biopsy, the sampling procedures and quantitation of defects. It appears necessary to investigate samples from different parts of the airways and quantitatively analyze the prominent lesions.

Abnormalities, Multiple↗