The Antley-Bixler syndrome: report of two familial cases with severe renal and anal anomalies.

UNLABELLED: The Antley-Bixler syndrome is characterized by premature closure of coronal and lambdoidal sutures, proptosis, depression of the nasal bridge, brachycephaly, radio-humeral synostosis and bowing of ulnae and femora associated with fractures. Most cases have been reported after birth with only one case diagnosed prenatally after recurrence of this autosomal recessive syndrome. The two present cases are of interest because of prenatal diagnosis of renal agenesis in the first case and early detection of clinical signs during the second pregnancy. Beside the unusual severity of the renal abnormalities, both cases had an imperforate anus in addition to the more common genital abnormalities. CONCLUSION: Renal agenesis and imperforate anus may occur in the Antley-Bixler syndrome.

Immunohistochemical localization of insulin-like growth factor I (IGF-I) in the rat epididymis.

The distribution of insulin-like growth factor I (IGF-I) was studied by immunohistochemistry during postnatal development of the rat epididymis. At 2 weeks the immunoreactivity was mainly located along the cytoplasmic apical border in both the caput and the cauda epididymidis. A slight immunolabeling was present in the myofibroblastic cells. Afterward, the epithelial immunoreactivity was minimal at 4 weeks and increased progressively after the 6th week, especially in the apical and subapical cytoplasmic compartments of the caput epididymidis. The labeling of the epithelial cells of the cauda epididymidis was restricted to the apical cytoplasmic area. Immunolabeling was also found in the myofibroblastic cells and was more intense after 6 weeks. The variations of the pattern of distribution support the hypothesis of a physiological role for IGF-I in the regulation of epididymal functions.

Laminin ultrastructural immunolocalization in rat testis during ontogenesis.

The synthesis of one of the main glycoproteins of the basement membrane, the laminin, was demonstrated by ultrastructural immunolocalization during rat foetal (16th day to 20th day of gestation) and postnatal development of the testis. The lamina densa, part of seminiferous tubular basement membrane, is labeled uniformly at all studied stages. The lamina lucida is not well defined before the postnatal stages, at which times discrete immunostaining extends from the lamina densa to the adjacent seminiferous epithelial cells (spermatogonia and Sertoli cells). The extracellular matrix around the peritubular cells is not labeled before birth. Intracellular immunostaining was detected as early as the 16th day of gestation in both Sertoli cells and cells around the seminiferous tubules which will transform later into peritubular cells. It was located in rough endoplasmic reticulum (RER) cisternae and secretory vesicles. After 18-20 days of postnatal life, the immunostaining faints progressively. Some positive material is seen in the RER of the gonocytes at all studied stages. Sertoli cells and peritubular cells are the main producing cells of laminin after the 16th of gestation. The laminin secreted by gonocytes may play an important role in adhesion of gonocytes to the lamina densa and adjacent Sertoli cells before their transition from basal compartment to adluminal compartment.

Growth hormone response following growth hormone releasing hormone injection in thalassemia major: influence of pubertal development.

Thirty-five patients with thalassemia major, aged 7 to 21 years, were studied to define the relationship between the pubertal development and the growth-hormone (GH) secretion during sleep, after administration of GH-releasing factor (hpGRF 1-44), and betaxolol-glucagon or arginin-insulin. Pubertal development was classified as being appropriate or delayed for chronological age. GH response to pharmacological stimuli and during sleep was not linked to the pubertal development according to the chronological age. The peak of GH secretion after GHRH injection was significantly delayed in thalassemic patients with retarded puberty. The integrated secretion of GH during the 120-min test was slightly but not significantly reduced in these patients. The prepubertal pattern of GHRH response was restored in the patients receiving substitutive therapy by HCG or testosterone. The alteration of GH response to GHRH in thalassemic patients is likely to be only due to delayed puberty and decreased endogeneous GHRH secretion since it is corrected by androgen or gonadotropin replacement.

Extracellular matrix biosynthesis by cultured fetal rat lung epithelial cells. I. Characterization of the clone and the major genetic types of collagen produced.

A new cell line of fetal rat lung origin has been established using the outgrowth procedure. One clone (2G3) isolated by this procedure exhibited during early passages some of the transmission electron microscopic features (e.g., lamellar bodies) indicative of type II pneumocytes and was selected for further study. This cell line has a stable modal chromosome number of 44 and has not been found to develop tumors in athymic rodents. The clone exhibits a biphasic growth curve with an initial generation time of approximately 22 hours at 37 degrees C. The cultures are not contact inhibited but rather develop an organized secondary growth pattern. Initially after subculture, a monolayer is formed consisting of cells which exhibit a cobblestone appearance. After development of this monolayer, a secondary growth pattern emerges. This latter phase of growth is characterized by spindle-shaped cells displaying a pattern of organization that delimits lumina on top of the initial monolayer. At the ultrastructural level, desmosomes are observed, and concurrent with the development of the secondary growth pattern, there is the appearance of dense cytoplasmic structures which resemble lamellar bodies. Based upon the origin, growth properties, and morphologic features of the cells, this clone has been designated fetal rat lung epithelial (FRLE) cells. The collagens secreted into the culture medium and present in the cell layers of FRLE cell cultures, which have developed the secondary growth pattern, were isolated using limited pepsin digestion and differential salt fractionation. Polyacrylamide gel electrophoresis under denaturing conditions indicated that FRLE cells synthesized components corresponding to the chains present in types I, III, IV, and V collagen molecules with no major differences occurring between the profiles of cell-associated and secreted molecules. Carboxymethyl-trisacryl chromatographic analysis revealed that approximately 80% of the collagen synthesized was type I and that approximately 20% of this genetic type of collagen was recovered as the type I homotrimer. Types III, IV, and V molecules accounted for 16, 2, and 3%, respectively, of the total collagen synthesized. Additionally, the type V collagen synthesized by FRLE cells was found to have the molecular compositions alpha 1(V) alpha 2(V) alpha 3(V) and [alpha 1(V)]3. These observations suggest that the collagen biosynthetic profile of the fetal or immature type II cell may differ from that of the fully differentiated type II pneumocyte. Furthermore, it is proposed that cultured FRLE cells may be a useful in vitro model system for investigating the regulation of macromolecular synthesis in and the differentiation and maturation of the fetal alveolar epithelial cell.

Immunolocalization of type IV collagen and laminin during rat gonadal morphogenesis and postnatal development of the testis and epididymis.

The distribution of type IV collagen and laminin was studied by immunocytochemistry during rat gonadal morphogenesis and postnatal development of the testis and epididymis. Immunostaining appeared as early as the 12th day of gestation along the basement membranes of the mesonephric-gonadal complex. The connection between some mesonephric tubules and coelomic epithelium was seen between the 12th and 13th day of gestation. Discontinuous immunostained basement membranes delineated the differentiating sexual cords in 13-day-old fetuses; this process probably began in the inner part of the gonadal ridge. The seminiferous cords surrounded by a continuous immunoreactive basement membrane are separated from the coelomic epithelium by the differentiating tunica albuginea in 14-day-old fetuses. During the postnatal maturation of epididymis and testis, the differentiation of peritubular cells is accompanied by a progressive organisation of the extracellular matrix into a continuous basement membrane. This change is associated with a gradual condensation of peritubular cells inducing an increase of immunostaining. In adult animals, the tubular wall of epididymis is thicker than the lamina propria of seminiferous tubules. Both type IV collagen and laminin immunostaining paralleled during ontogenesis at the light-microscope level.

[Otologic signs and early diagnosis of Turner syndrome. Reevaluation of 30 cases]. / Signes otologiques et diagnostic précoce du syndrome de Turner. Réévaluation sur 30 cas.

In most occasions the Turner's syndrome is diagnosed on the basis of severe growth retardation. But the possibility of an effective treatment of short stature requires earlier a diagnosis. Among the other signs, the importance of ORL signs is underestimated. A group of 30 patients has been analysed to determine their precise extension. The external ears are frequently prominent, low-set and/or posteriorly rotated. Frequency and chronicity of otitis media is highlighted by hypoacousy of the transmission type. The perception pathology is far less common and seems being independent of middle ear pathology. A abnormal development of the 1st branchial arch is likely to explain the auricular pathology in view of the frequently associated anomalies of the palate and the dental articulation. One must clearly consider the diagnosis of Turner syndrome in the case of chronic auricular pathology associated with low linear velocity in a young girl allowing for earlier diagnosis.

Anionic sites of the basement membrane of rat seminiferous tubules during ontogenesis.

The anionic sites of the basement membrane of rat seminiferous tubules were demonstrated ultrastructurally in the lamina densa by using cationic polyethyleneimine (PEI). The sites were largely digested out after incubation with heparitinase, indicating a large proportion of heparan sulfates. The anionic sites were present as early as day 16 of gestation on the interstitial side of the lamina densa, and after gestation day 20 they were symmetrically organized on both sides of the lamina densa. The number of sites is not modified postnatally. They appear more irregular in density with advancing age. Experimental conditions as cryptorchidism, fetal irradiation, and ligation of the ductuli efferents lead to unspecific alterations in the distribution of the anionic sites that are parallel to the modifications in the basement membrane.

Anionic sites in the basement membrane of the rat epididymal epithelium during ontogenesis and after testicular and gonadal tract lesions.

Anionic binding sites in the lamina densa of the basement membrane of the rat epididymal epithelium were demonstrated ultrastructurally with the use of cationized polyethyleneimine (PEI). Enzyme digestion with heparitinase removed the anionic sites, indicating that they consist largely of heparan sulfates. The anionic sites are present as early as the 16th day of gestation on the interstitial face of the lamina densa; later during gestation they are localized on both faces of the lamina densa without further modification after birth. The distribution of the anionic sites was identical all along the epididymal duct. After castration and ligation of efferent ducts or in the state of cryptorchidism the sites were more numerous and located inside the thicker portion of the lamina densa. These alterations were more prominent in the initial segment compared to the distal segments, suggesting a differential androgen dependence of the reactive sites and their patterns of distribution.

[Genetic aspects of congenital adrenal hyperplasia due to 21-hydroxylase deficiency]. / Aspects génétiques de l'hyperplasie congénitale des surrénales par déficit en 21-hydroxylase.

The variability of clinical and biological expression of the 21 OH hydroxylase deficiency is likely to be related to genetical variability. Beside the well known autosomic recessive mode of inheritance the frequencies of the different forms of the disease, especially the classical and late onset form, have been more precisely defined through neonatal screening programs for the classical form which lead to a frequency of about 1 case/20,000 with a calculated gene frequency around 1/140. The linkage with the major histocompatibility complex allows the location of the putative locus of the 21 OH ase on the short arm of the chromosome 6 in the class III of the MHC. This linkage has made possible a better fetal diagnosis even if some pitfalls as recombination must be kept in mind. On the basis of clinical conditions the abnormal genes are likely to be considered as an allelic series with a least two main types of pathological alleles: the "severe" and "moderate". During the last two years, taking advantages of molecular gene biology, the structure of the normal human 21 OH ase gene has been studied. It exists as duplicate genes in close relation with the gene of the fourth component of the complement. A deletion of one of the copy has been demonstrated in the form associated with the BW47 MHC haplotype. It is likely that during the coming years genetical heterogeneity will be demonstrated as it has been for other genetic diseases as thalassemia.

[Lesions of the basal ganglia in mumps. Clinical and neuroradiological development in a case]. / Lésions des noyaux gris centraux au cours des oreillons. Evolution clinique et neuroradiologique d'un cas.

Among mumps complications, encephalitis is the most frequent. Involvement of the basal ganglia has been previously reported associated to some other encephalic lesions. In one case, changes were confined to basal ganglia and occurred at the 10th day of evolution of mumps. Clinically a bilateral extrapyramidal syndrome was present without other neurological disorders. CT scan showed bilateral lesions in the area of the basal ganglia. The course was favorable. The neurological examination and CT scan were normal 6 months later. Such complications should be prevented by vaccination.

Ultrastructural study of epithelial cells and basement membrane. Differentiation of the rat epididymis after prenatal irradiation.

The effects of prenatal irradiation on the testis are well documented, but less is known about its effects on epididymal differentiation. Pregnant rats were irradiated on the 18th day of gestation. The increase in microfilaments and lipid inclusions in the epithelial cells, in favor of a direct radiation effect, is maximal at birth and disappears thereafter. Narrow cells and clear cells show a normal differentiation pattern. On the other hand, the principal cell maturation is largely altered. The synthesis capacities are decreased based on a reduction in the size of the Golgi apparatus and the smooth endoplasmic reticulum. The aspects of invaginations of the apical plasmalemma, coated vesicles and multivesicular bodies are not modified, suggesting normal absorption functions. The epithelial basement membranes become irregular and thicker than normal, enfolding the basal part of the epithelial cells. The basement membrane proteoglycans, demonstrated by the cationic marker polyethyleneimine, are irregularly distributed in contrast to the normal pattern. These modifications of the principal cells and the basement membrane are more prominent in the proximal epididymis. This suggests a differential maturation dependence of the epithelial cells on the luminal factors, normally secreted by the testis, and likely disturbed by prenatal irradiation which leads to germ cell degeneration, and then to a new balance in the seminiferous epithelium.

[Ultrastructural analysis of anionic sites of the basal membrane of the seminiferous tubules of subjects with severe oligospermia]. / Analyse ultrastructurale des sites anioniques de la lame basale du tube séminifère de sujets présentant une oligospermie sévère.

Several morphological alterations of the basement membrane of the seminiferous tubules have been reported in the patients presenting with a testicular sterility. The proteoglycans are one of the major components of the basal membrane and may be ultrastructurally defined by the use of the cationic marker polyethyleneimine (PEI). In comparaison to the normal distribution of the anionic sites labelled by PEI which is characterized by a regular pattern of distribution along both the epithelial and the interstitial faces of the lamina densa, the pattern of distribution of the sites is largely altered in 6 patients, 27 to 40 years of age, with oligo- or azoospermia. Several types of alterations are reported: parallel thickening of the lamina densa with an abnormal distribution of the anionic sites inside the lamina densa, stratifications of the basal membrane depressing the seminiferous epithelium with anionic sites labelled on both faces of the lamina densa-like layers, massive expansions of the lamina densa with either a regularly circumferential labelling of the sites or a random type of distribution. The digestion of the sites by the enzyme heparitinase is highly suggestive of the presence of proteo-heparan-sulfate. The analysis of the distribution of the anionic sites may represent a usefull tool for studying the pathogenesis of testicular sterility.

Influence of testicular secretions on epididymis oxidative metabolism in the rat.

The oxidative metabolism of the epididymis has been investigated in 40-day-old rats under normal and experimental conditions. No difference in the oxidative metabolism was observed between the initial, middle and terminal segments of the epididymal duct of normal rats. After bilateral or unilateral castration or efferent duct ligation, the oxidative metabolism was found to be exclusively dependent upon plasmatic androgens in the terminal segment in contrast to the proximal segment oxidative metabolism which is dependent of both normal luminal secretions and normal plasmatic androgens.

[Hyalinosis cutis and mucosae. Ultrastructural histochemical aspects indicating intracellular accumulation of glycosaminoglycans]. / Hyalinose cutanéo-muqueuse. Aspects histochimiques ultrastructuraux en faveur d'une surcharge intracellulaire en glycosaminoglycannes.

The exact nature of the genetic defect of hyalinosis cutis et mucosae or d'Urbach-Whiete syndrome is still matter of controversy. The present article reports on three new cases in which several different ultrastructural and biochemical investigations add more arguments to support an anomaly of the glycosaminoglycans degradation in the dermal fibroblasts. Cationic dyes as polyethyleneimine and alcian blue show an intense ultrastructural staining of the abnormal basal laminae and the intracellular lysosomal bodies in cultured fibroblasts. These are related to the accumulation of anionic charged proteoglycans. The primary defect of hyalinosis cutis et mucosae is likely due to a lysosomal defect so far not biochemically defined.

Plasma 6-keto prostaglandin F1 alpha and thromboxane B2 in sick preterm neonates.

To determine if vascular abnormalities in preterm neonates might be related to vasoactive prostaglandins, stable prostacyclin (6-KPGF1 alpha) and thromboxane A2 (T X B2) metabolites in arterial blood were measured at less than or equal to 6 hours after birth and at 24, 48, and 72 hours using a radioimmunoassay. Neonates of less than 32 weeks gestation (N = 26) were diagnosed as having either the idiopathic respiratory distress syndrome (IRDS, N = 15) or pulmonary edema (PE, N = 11), and were also grouped according to the presence or absence of intracranial hemorrhage (ICH, N = 11) or patent ductus arteriosus (PDA, N = 10). Initial plasma 6-KPGF1 alpha was greater in neonates with ICH (0.23 +/- 0.04 ng/ml, mean +/- SE) than without ICH (0.11 +/- 0.04, p less than 0.05). Neonates with both ICH and IRDS (N = 8) had significantly elevated T X B2 at all sampling times compared to neonates with IRDS and no ICH (N = 7). Both T X B2 and 6-KPGF1 alpha increased with time in those with major ICH. Among neonates without ICH, 7 with IRDS had higher initial 6-KPGF1 alpha (0.19 +/- 0.07 ng/ml) and lower T X B2 (0.15 +/- 0.04 ng/ml) than 8 with PE (0.04 +/- 0.01 and 0.37 +/- 0.09 ng/ml, respectively). The initial 6-KPGF1 alpha (0.024 + 0.003 ng/ml), measured in neonates with PE and without PDA or ICH (N = 6), was significantly less than the corresponding value in the other neonates (0.201 +/- 0.036 ng/ml) (N = 20).