Expression of inducible nitric oxide synthase and effects of L-arginine on colonic nitric oxide production and fluid transport in patients with "minimal colitis".

OBJECTIVE: Some patients with idiopathic, chronic diarrhoea have minimal, non-specific colonic inflammation. As nitric oxide (NO) acts as a secretagogue in the colon, we studied the expression of inducible NO synthase (iNOS) in mucosal biopsies and the effects of NOS stimulation on colonic transfer of fluid and output of NO in patients with "minimal colitis". MATERIAL AND METHODS: Twelve patients with idiopathic, chronic diarrhoea and "minimal colitis" and 6 healthy volunteers were included in the study. Expression of iNOS in colonic mucosal biopsies was quantified by Western blot analysis and localized by immunohistochemistry. The effects of topical L-arginine or placebo on colonic net fluid transfer and nitrite/nitrate (NOx) output were assessed during "steady state" perfusion of the whole colon. Concentrations of NOx were measured by Griess' assay. RESULTS: The expression of iNOS was increased 10-fold (p<0.01) in patients with "minimal colitis" compared with that in healthy volunteers and localized to the colonic epithelium. Colonic absorption of fluid was impaired (mean (SEM) 1.5 (0.2) versus 3.0 (0.2) ml/min, p<0.001) and the output of NOx was increased (47 (4) nmol/min versus <37 nmol/min, p<0.05) in patients with "minimal colitis" compared with that in healthy volunteers. Luminal L-arginine (20 mM) reduced colonic absorption of fluid in both groups (95% confidence intervals (CIs) 21-50% in patients with "minimal colitis" versus 4-18% in healthy volunteers), but an increase in NOx output was detectable only in the group of patients (8-106%). In time control experiments, colonic net transfer rates of fluid and outputs of NOx were unaffected by placebo. CONCLUSIONS: In patients with idiopathic, chronic diarrhoea and histopathological evidence of "minimal colitis", colonic absorption of fluid is impaired, while epithelial expression of iNOS and mucosal production of NO is enhanced. It could be speculated that NO in excess contributes to the diarrhoea observed in "minimal colitis".

p75-NGFR expression in the human prenatal pituitary gland.

The aim of this study was to elucidate the distribution of nerve growth factor receptor (NGFR) in the prenatal human pituitary gland until 21 weeks of gestation. Eight fetuses, with gestational ages from 13 to 21 weeks, were examined. The midaxial tissue block from the cranial base, including the pituitary gland and the sella turcica, was excised from the fetuses. The tissue was decalcified, embedded in paraffin, and cut in serial sections in 4-micro thicknesses. Immunohistochemistry was performed with monoclonal antibody p75-NGFR. p75-NGFR immunoreactivity was observed in fetuses from 15 weeks of gestation in the borderline between pars intermedia and the neurohypophysis.

Subclassification of anencephalic human fetuses according to morphology of the posterior cranial fossa.

Anencephaly is a designation for congenital absence of the cranial vault with cerebral hemispheres completely missing or decreased to small masses attached to the base of the skull. The etiology is unknown. Whether the bony tissue or soft brain tissue is a primary factor is also unknown. The present study has focused on the posterior cranial fossa in anencephaly. The goal is to determine whether differences in the posterior cranial fossa could provide a basis for subclassification of anencephalic fetal skeletons. Twenty-three human anencephalic fetuses, at gestational ages 13 to 22 weeks, were studied. Radiologic and cephalometric analyses, including measurements of bone sizes and different angles, were performed. Permission for autopsy of the central nervous system was not available. For comparison of anencephalic findings with normal conditions, standards from a recent publication were used. Foot length served as a parameter for age comparison. The study showed 2 morphologic types of the posterior cranial fossa. One type had a fossa cranial morphology close to normal morphology, whereas the other had a malformed and much smaller posterior cranial fossa. The latter condition was presumed to be due to a primary error in chondral and cranial development. The current skeletal subgrouping might be essential for clinicians' or pathologists' future assessment of the autopsy results. The skeletal subgrouping should, if possible, be associated with karyotyping and analysis of the central nervous system. The goal is to distinguish between congenital conditions resulting in anencephaly and acquired conditions resulting in anencephaly.

Nerve growth factor receptor immunolocalization during human palate and tongue development.

OBJECTIVE: To investigate the temporospatial pattern of nerve growth factor receptor (NGFR) immunolocalization during human palatal closure. MATERIALS: Human palate and tongue tissues from 33 embryos/fetuses, 9 to 22 weeks of fertilization age. METHODS: Tissues were divided according to developmental stage and palatal development (before, during, and after closure) and then subjected to decalcification, paraffin embedding, serial sectioning, survey staining, and p75NGFR immunohistochemical staining. RESULTS: Specific temporospatial patterns of p75NGFR reactivity were observed; reactivity was intense in the soft tissue palatal shelves before and during palatal closure and was weaker in the palate after palatal closure. In the tongue, intense reactivity was seen throughout 9 to 22 weeks. CONCLUSION: The observed patterns suggest that p75NGFR may enable the visualization of physiological events in palatal closure during normal human development.

Midline skeletodental morphology in holoprosencephaly.

OBJECTIVE: The purpose of the present study was to analyze histologically the midline structures in a human fetus with holoprosencephaly and a single median maxillary central incisor. METHODS: A human male fetus, CRL 137 mm, postconceptional age 18 weeks, with a diagnosis of holoprosencephaly, the cebocephalic type (one nostril), and alobar brain development, was investigated. After radiography, the cranial midline structures were examined histologically. RESULTS: The histological examination revealed partial absence of the intermaxillary suture (in the region anterior to the central incisor), absence of the internasal suture, and partial absence of the metopic suture (caudal part). A single midline nasal bone was observed instead of two bilateral nasal bones, and a midline maxillary central incisor was found instead of two bilateral incisors. A short nasal septum, absence of crista galli, and partial absence of cartilaginous tissue anterior to the sella turcica in the region of the presphenoid bone were recorded. CONCLUSIONS: The study shows that in the affected fetus, there were malformations of midline structures anterior to the sella turcica comprising suture development and cartilage development.