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Biomedical subjects

J M Lauweryns

Publications and source records attributed to J M Lauweryns.

At least 19 recordsLinked to original sources

Postnatal maturation of neuroepithelial bodies and carotid body innervation: a quantitative investigation in the rabbit.

The intrapulmonary airways contain oxygen-sensitive chemoreceptors which may be analogous to the arterial chemoreceptors: the neuroepithelial bodies (NEB). While the NEB are prominent in the neonatal lung, physiological studies indicate that the carotid bodies are still relatively inactive at birth. This points to an unequal degree of development of both during the early neonatal period. As a reflexogenic chemoreceptor function depends on a well-developed innervation, we undertook a comparative investigation of the development of the NEB and the carotid body glomus cell innervation. Two morphological aspects of the innervation of NEB and carotid body glomus cells were quantified in rabbits of different age groups. The total sectional area of intracorpuscular and intraglomerular nerve endings per NEB or glomus cell group, respectively, was measured and the area percentage of mitochondria and synaptic vesicles was determined. In the NEB, no significant difference in total sectional area of the nerve endings between the age groups was observed, while in the carotid body there was a significant increase in the adult age group. In addition, the area percentage of mitochondria and synaptic vesicles of the nerve endings did not change significantly with age in the NEB, while in the carotid body these increased and decreased, respectively, with age. These observations point to a shift from morphologically efferent nerve endings, rich in synaptic vesicles, to morphologically afferent nerve endings, rich in mitochondria. Our interpretation of these findings is that, at birth, the NEB innervation is more mature than the carotid body glomus cell innervation and that the latter matures at a later time than the former. These findings support the theory that the NEB may act as complementary chemoreceptors to the carotid body during the early postnatal period.

Age Factors↗

The pulmonary neuroendocrine system: the past decade.

The pulmonary neuroendocrine system consists of specialized airway endocrine epithelial cells, associated with nerve fibres. The epithelial cells, the pulmonary neuroendocrine cells (PNEC), can be solitary or clustered to form neuroepithelial bodies (NEB). During the last thirty years, the pulmonary neuroendocrine system has been intensively investigated and much knowledge of its function has been obtained. This text reviews work which dates from the last ten years. In this period, the picture of the pulmonary neuroendocrine system we previously had, has not fundamentally changed. The pulmonary neuroendocrine system is still regarded as an oxygen sensitive chemoreceptor with local and reflex-mediated regulatory functions, and as a regulator of airway growth and development. Continuing research has much more refined this picture. This text reviews several aspects of the pulmonary neuroendocrine system: phylogeny, the amine and peptide content of its epithelial cells, ontogeny and influence on lung development, the influence of hypoxia and nonhypoxic stimuli, immunomodulatory function, innervation and pathology. Among the discoveries of the past decade, three stand out prominently because of their great significance: additional proof that the neural component of the pulmonary neuroendocrine system is sensory, sound experimental evidence that PNEC stimulate airway epithelial cell differentiation and the discovery of a specific membrane oxygen receptor in the PNEC.

Adjuvants, Immunologic↗

Pulmonary neuroepithelial bodies are innervated by vagal afferent nerves: an investigation with in vivo anterograde DiI tracing and confocal microscopy.

The pulmonary airway and alveolar epithelia contain distinctly innervated clusters of basally granulated cells: the neuroepithelial bodies. In the past, morphological criteria and the results of selective vagotomy have led to the interpretation that their innervation is sensory. Consequently, they are regarded as receptor organs. As a further test of this hypothesis, the present investigation set out to label vagal sensory nerve fibres to the lungs by anterograde neural tracing, and to establish the relationship between these fibres and the neuroepithelial bodies. A fluorescent neural tracer was injected unilaterally into the left or right nodose ganglion of adult rats. After suitable survival times, thick frozen sections of lung tissue were studied with laser scan confocal microscopy. Sensory nerve fibres were seen to run in the airway walls and occasionally penetrated the epithelium, where they formed complex terminals. The resulting intraepithelial sensory end organs showed a close morphological resemblance to the neuroepithelial bodies. Subsequently, electron microscopic investigation of such identified structures revealed the typical ultrastructural characteristics of neuroepithelial bodies: corpuscular cells containing dense cored secretory vesicles and contacted by mitochondria-rich nerve endings. We conclude that anterograde tracing of sensory nerves from the nodose ganglion confirms the receptor nature of the pulmonary neuroepithelial bodies, which may correspond to a subpopulation of the irritant and C-fibre receptors.

Animals↗

Lymphocytes and dendritic cells in the normal uterine cervix. An immunohistochemical study.

OBJECTIVE: Assessment of the appearance, distribution and numerical density of immune cell populations in the normal human uterine cervix. STUDY DESIGN SETTING: University Hospital Gasthuisberg. SUBJECTS: 29 healthy women undergoing total hysterectomy for non-cervical benign uterine disease. ANALYSIS: Immunohistochemistry and morphometrical analysis on histological sections containing ectocervix, transformation zone and endocervix, using antibodies against the following antigens: HLA-DR, CD4, CD22, CD1a and CD8. STATISTICAL ANALYSIS: Wilcoxon rank sum test. RESULTS: Lymphocytes in the epithelial and stromal compartments are predominantly T-lymphocytes. Intraepithelial T-lymphocyte and Langerhans' cell densities and their distribution are not influenced by the menstrual cycle and are the same in both ectocervix and transformation zone. CONCLUSION: The wide variation of T lymphocyte subpopulations and Langerhans' cell densities in the normal epithelium of the uterine cervix is stressed. We are the first to present a large and well-defined control series, which is indispensable to study the effect of smoking and other factors on the cervical immune system.

Adult↗

Postnatal development of the pulmonary neuroepithelial bodies in various animal species.

Various aspects of the postnatal development of intrapulmonary neuroepithelial bodies (NEB) were quantified in guinea-pigs, rabbits, cats, rats and hamsters. The highest densities of NEB were found at birth, especially in species with very immature neonates. Postnatally this density decreased, most probably by lung expansion and growth. The number of corpuscular cells per NEB generally did not change during postnatal development. Likewise, the volume density of their secretory dense cored vesicles remained unchanged. On the other hand, in most species and especially in those with very immature neonates, the number of intracorpuscular NEB nerve endings increased during postnatal development. At the same time, the number of afferent nerve endings increased at the expense of the efferent ones. We argue that NEB serve a dual function: endocrine and chemoreceptor. The endocrine function, dependent on the number of cells and their content of secretory vesicles, is already well developed at birth and does not mature further. The chemoreceptor function, dependent on the innervation, shows considerable maturation in the postnatal period.

Animals↗

Immunoreactivity for the alpha-subunit of the pituitary glycoprotein hormones in pulmonary neuroendocrine cells of developing human lung and various perinatal diseases.

Infant lung tissue, obtained at autopsy, was studied by immunohistochemistry for the presence of pituitary glycoprotein hormones (PGHs) in the lung. The infants, born at term or preterm, died of various causes. The results provide the first immunological evidence of the presence of the common a-subunit of the pituitary glycoprotein hormones (alphaPGH) in the lung. The immunoreactivity is located in the pulmonary neuroendocrine cells and neuroepithelial bodies. In addition, the cells labelled by alphaPGH antisera (alphaPGH cells) form a subpopulation of the neuroendocrine cells detected by anti-calcitonin immunohistochemistry (CT cells). Moreover, the number of alphaPGH cells appears to increase after neonatal pneumonia or when the number of CT cells is elevated following the development of disease. Also, the weak staining of one of the monoclonal antibodies against the specific b-subunit of thyrotropin (TSH) might, in combination with the increased detectability of a-subunits, indicate that TSH can be endogenously produced in the lung.

Antibody Specificity↗

NCAM expression in the pulmonary neural and diffuse neuroendocrine cell system.

Neural cell adhesion molecule (NCAM)--a membrane protein involved in cell-cell adhesion within the central and peripheral nervous systems--was demonstrated to be a sensitive and specific marker for neuroepithelial bodies (NEB) and neural tissue elements in the cat lung. Using the streptavidin-biotin immunoperoxidase method, NCAM reactive sites were investigated with monoclonal and polyclonal antibodies on serial section of Bouin fixed, paraffin embedded lung tissue. Moreover, NCAM expression was compared with that of neuron-specific enolase (NSE) on adjacent sections. The most obvious NCAM staining was obtained with the monoclonal antibody. From newborn to adult life, cell surface labeling was identified on NEB cells. In mature cat lung, they were no longer positive. Solitary neuroendocrine cells (NEC) were always negative. In contrast to the transient postnatal immunoreactivity of NEB cells, nerve fibers and ganglion cells were stained throughout all life stages and studied. The distribution of NCAM in NEB, nerve fibers and ganglion cells was similar to that NSE, except in the adult lung. This study reveals that during lung growth shared NCAM antigens exist between the pulmonary nervous and endocrine system, whereas in mature lung NCAM proteins are confined to neural tissue elements. The difference in NCAM expression between NEB and NEC might suggest an involvement of NCAM in the formation of contacts between NEB cells and nerves.

Animals↗

The effect of pregnancy on endometriosis in baboons (Papio anubis, Papio cynocephalus).

BACKGROUND: This study was performed to test the hypothesis that endometriosis undergoes regression during pregnancy. METHODS: This study was performed on 11 baboons with histologically proven endometriosis, housed at the Institute of Primate Research, Nairobi, Kenya. In each individual baboon paired laparoscopies were performed prior to and during pregnancy (6 during first and 5 during second trimester of gestation) with an interval of 5 +/- 3 months. During each laparoscopy the number, size and type of endometriosis implants were noted in detail on a pelvic map; the endometriosis score and stage were calculated according to the revised American Fertility Society (AFS) classification. In each baboon the observations prior to and during pregnancy were compared and analysed by Wilcoxon signed rank test (two-tailed). RESULTS: No significant change was observed in the AFS score or stage of endometriosis, or in the number, size and type of endometriotic lesions in baboons during gestation when compared to the nonpregnant state. CONCLUSION: In baboons pregnancy had no significant effect on endometriosis during the first or second trimester of gestation.

Animals↗

Effects of postnatal age and of thymectomy on hamster pulmonary neuroendocrine system and aspects of programmed cell death.

Effects of postnatal age and neonatal thymectomy on the numbers and characteristics of pulmonary neuroepithelial bodies (NEB) were investigated in 14-day- compared with 2.5-month-old hamsters. Left lung sections were stained for the marker PGP 9.5 and used for light-microscopic quantification, while the right lungs were processed for an electron-microscopic survey of the NEB ultrastructural features. For the first time, it is clearly demonstrated that, depending on the sampling method, the number of NEB may rise or fall with age; when considering the entire lung volume, the actual number of NEB doubles, whereas when studying a constant surface area, their number apparently decreases. Also, the proportion of alveolar NEB as well as luminal contact increase on normal development. In neonates, in contrast to older animals, apoptosis is clearly present in NEB, and approximately 10% of the NEB are associated with inflammatory cells. In some cases, the dead cells have properties of both apoptosis, disintegration and cytoplasmic degeneration. The presence of intracorpuscular neutrophilic granulocytes correlates with cellular death and innervation of the NEB. Thymectomy causes only minor effects on the pulmonary neuroendocrine system. It is argued that development of the NEB and of their innervation continue during the postnatal period.

Animals↗

Elastogenesis is linked to epithelial-stromal interactions in postnatal hamster bronchioles.

In a previous study, direct epithelial-stromal cell contacts via foot processes perforating the basement membrane were investigated in bronchioles of postnatal hamster lungs. In the present study, analogous postnatal epithelial foot processes have been found on stromal cells exhibiting active elastogenesis as determined by morphological criteria. In addition, elastin is prominently present close to the epithelium, but less so in the deeper layers, in the bronchioles of the 14-day-old hamster. The elastin often has an asymmetrical distribution around the subepithelial fibroblast with preference for secretion toward the epithelium. Thus, elastogenesis can now be linked to epithelial-stromal interactions at the temporal, functional, and morphological levels.

Animals↗

Langerhans' cells and L1 antigen expression in normal and abnormal squamous epithelium of the cervical transformation zone.

This study evaluates the presence of Langerhans' cells and expression of L1 antigen in squamous epithelium of the normal and dysplastic transformation zone of the cervix uteri and determines the influence of tobacco smoking and pregnancy. Women who smoked and pregnant women showed a decrease of Langerhans' cell counts in normal epithelium. In cervical intraepithelial neoplasia (CIN) 1 lesions, decreased Langerhans' cell counts were noted. L1 antigen expression was significantly less in CIN of all grades. Normal squamous epithelium of smokers showed weaker staining for L1 antigen but total staining scores were not significantly different. These data suggest a decrease in epithelial cell-mediated immune response in smokers, pregnant women and in low-grade CIN. Dysplastic squamous cells probably have intracellular regulatory problems independent of other immune cells.

Adult↗

Cervical cotinine and macrophage-Langerhans cell density in the normal human uterine cervix.

Cotinine levels in blood and cervical fluid of smokers and non-smokers were analysed using capillary-column gas chromatography. These levels were not related to numerical cell densities of intraepithelial S100-protein- and LN2-positive Langerhans cells or to MAC-387-positive macrophages in the stroma of the transformation zone of normal uterine cervices. A decrease in the number of Langerhans cells was noted in smokers, especially in those using oral contraceptives (OCs). Macrophages were more numerous in the endocervical stroma of smokers, suggesting a local response to smoke constituents. These findings may indicate a synergistic suppression of local cervical immunity by smoking and OCs.

Adult↗

The prevalence of spontaneous endometriosis in the baboon (Papio anubis, Papio cynocephalus) increases with the duration of captivity.

BACKGROUND: It is not known whether stress affects the prevalence of endometriosis in women. Baboons with spontaneous endometriosis may be interesting models to study the human disease. For baboons, living in captivity is a period of chronic stress without continuous exposure to pregnancy. This study was done to compare the prevalence of endometriosis between baboons recently captured in the wild and those living in captivity for several years. METHODS: A diagnostic laparoscopy was performed for screening endometriosis and obtaining biopsies in 104 female baboons including animals that had been captured in the wild less than 1 year ago (n=52, Group I), primates that had been living in captivity for one to two years (n=30, Group II) and animals that had been captured for more than two years (n=22, Group III). RESULTS: The prevalence of clinical and biopsy-proven endometriosis in all baboons was 17% and 12%, respectively. Clinical endometriosis was found more frequently in group III (32%) than in group II (17%) or group I (11%). The prevalence of biopsy-proven endometriosis was also significantly higher in group III (27%) than in groups I and II combined (8%, p=0.03). CONCLUSIONS: The results indicate that the prevalence of endometriosis increases with the time spent in captivity. This trend may be explained by more menstrual cycles uninterrupted by pregnancy in captive than in wild baboons, and possibly also by age-related factors or by captivity-associated stress.

Age Factors↗

Spatial and temporal distribution of 7B2 in the pulmonary diffuse neuroendocrine system of the cat.

The postnatal developmental profile of the presence of 7B2 was studied immunocytochemically in the pulmonary diffuse neuroendocrine system of the cat. Labelling was found in neuroepithelial bodies (NEB) but not in solitary neuroendocrine cells. The identity of NEB was confirmed on adjacent serial sections by the immunostaining for protein gene product 9.5, a pan-neuroendocrine marker. The first 3 weeks after birth 7B2 stained NEB were most abundant with a subsequent decline thereafter. The positive correlation between the variation of 7B2 immunoreactivity and number of NEB suggests an important role for 7B2 in NEB.

Animals↗

Pulmonary neuroepithelial bodies in neonatal and adult dogs: histochemistry, ultrastructure, and effects of unilateral hilar lung denervation.

In neonatal dogs, neuroepithelial bodies (NEB) are located in the distal lung. They consist of closely packed and granulated epithelial cells showing a positive immune reaction to serotonin and carrying well-developed apical microvilli. They make close contact with capillaries and form morphologically afferent synaptic junctions with intracorpuscular nerve endings. Since most nerve endings degenerate after hilar lung denervation, they are carried by extrinsic, most likely vagal, sensory nerve fibers. We conclude that pulmonary NEB probably are receptor organs, sampling the inspired air and secreting bioactive substances. These might have a local vaso- or bronchoactive regulatory effect, or could be carried to other body parts via the blood vessels. In addition, NEB might induce integrative reflexes via the central nervous system. The NEB intracorpuscular nerve endings also show spontaneous degeneration. This, in addition to the scarcity of NEB in the distal lungs of adult dogs, strongly suggests that the pulmonary NEB are particularly important during the perinatal period of life.

Aging↗

Association of immune cells with neuroepithelial bodies in the lungs of neonatal dogs, cats and hamsters.

A close topographical association between neuroepithelial bodies and immune cells is occasionally observed in the lungs of various neonatal mammalian species. The immune cells concerned are mast cells and neutrophil or eosinophil granulocytes. In the lungs of newborn puppies having undergone left lung autotransplantation, mast cells are particularly numerous in the airway mucosa of both right and left lungs and their association with neuroepithelial bodies is highly significant. Several of the substances known to be synthesized by the neuroepithelial bodies have a chemoattractive effect on immune cells. Thus, our observations indicate that intrapulmonary neuroepithelial bodies contribute to the local immune response.

Animals↗

Intrapelvic injection of menstrual endometrium causes endometriosis in baboons (Papio cynocephalus and Papio anubis).

OBJECTIVE: The Sampson hypothesis of retrograde menstruation as a cause of endometriosis was tested by determining the effect of intrapelvic injection of menstrual versus luteal endometrium on the incidence, peritoneal involvement, and stage of endometriosis. STUDY DESIGN: Seventeen baboons were injected retroperitoneally with luteal (n = 6) or menstrual (n = 7) endometrium and intraperitoneally with menstrual endometrium (n = 4). Laparoscopies were performed after 2 months in all animals and after 5 and 12 months in six and five primates injected with luteal and menstrual endometrium, respectively. RESULTS: The peritoneal endometriosis surface area, number of implants, and incidence of typical and red subtle lesions were significantly higher after retroperitoneal injection of menstrual than of luteal endometrium. By use of menstrual endometrium intraperitoneal seeding was more successful in causing endometriosis than was retroperitoneal injection. No significant changes in number or surface area of endometriotic lesions induced with retroperitoneal injection of luteal endometrium after 5 months were observed in the six baboons. At repeat laparoscopy 12 months after intrapelvic injection of menstrual endometrium progression was recorded in three of four regularly cycling animals, whereas regression was evident in one baboon that had become amenorrheic after induction. CONCLUSION: Intrapelvic injection of menstrual endometrium can cause peritoneal endometriosis and offers experimental evidence supporting the Sampson hypothesis.

Animals↗

Epithelio-stromal interactions in neonatal hamster bronchioles: morphology and distribution of epithelial foot processes and their possible relation to epithelial growth inhibition.

Morphology and distribution of epithelial foot processes (FP) were studied in hamster neonatal lung bronchioles. To correlate them with growth, bronchiolar mitotic index was determined, rat small intestine used as a reference tissue and the distribution of foot processes compared to the distribution of immunoreactivity against proliferating cell nuclear antigen (PCNA). In bronchioles, where growth occurs through dispersed mitoses, FP also occur dispersed throughout the whole perimeter of the epithelium; whereas in small intestine, where growth is localised in a specific region (crypts), FP are likewise confined to a distinct, but different, zone (villi). Staining the bronchioles for PCNA labels dispersed grouplets of nuclei; most of which being only weakly stained. In the intestines, strong immunostaining mainly occurs in the crypts, while the villi mainly display a weak nuclear stain. Additionally, in both types of tissue the distribution of FP and weak PCNA staining are parallel. Thus, an apparent association between FP, lack of proliferation and nucleoplasmic PCNA staining arises; the basis of which being presently unclear. However, a possible interrelating factor might be a growth inhibitory influence of epithelio-stromal interactions on the epithelial cells.

Animals↗