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Biomedical subjects

J I Rodriguez

Publications and source records attributed to J I Rodriguez.

At least 19 recordsLinked to original sources
PubMed2004

Decrease of parafollicular thyroid C-cells in experimental esophageal atresia: further evidence of a neural crest pathogenic pathway.

Adriamycin-induced experimental esophageal atresia (EA) is often associated with malformations of neural crest (NC) origin, such as abnormal pharyngeal pouch derivatives like the thymus and the parathyroids. The aim of the present study was to examine whether NC-derived thyroid C-cells were abnormal in a rat model. Pregnant rats received intraperitoneally either 2 mg/kg Adriamycin (EA) or vehicle (controls) on days 8 and 9 of gestation. Fetuses were recovered on day 21, and blocks including the trachea and thyroid were fixed in formalin, coronally sectioned at 3-mum widths, and stained with standard hematoxylin and eosin until the largest area of thyroid was reached. From this point on, the 1st, 10th, and 20th slices were immunohistochemically stained with anti-calcitonin antibody. Positively-stained cells in each section of the gland were counted using a computer-assisted image analysis method, and the results were averaged. The distribution of the cells within the gland was assessed as well. Comparisons between EA and control rats were made by nonparametric tests with a significance threshold of p<0.05. The number of C-cells was dramatically reduced in EA animals compared with controls (32.4+/-36 vs. 92.3+/-60.5, p<0.001). Histology of the thyroid was similar in both groups, but the distribution of positive C-cells within the gland followed an abnormal pattern in EA rats. Adriamycin causes a pattern of NC-derived malformations, including a severe decrease in thyroid C-cells accompanied by abnormal distribution or migration patterns. These results represent further evidence of the involvement of NC organogenic control dysregulation in the pathogenesis of EA and its associated malformations. The similarities between the rat model and the clinical picture strongly support investigating other subclinical NC-derived anomalies in patients with EA.

Animals↗
PubMed2003

The adrenal cortex in experimental congenital diaphragmatic hernia.

BACKGROUND/PURPOSE: Adrenal cortical malfunction was found recently in patients with severe congenital diaphragmatic hernia (CDH). The current study tests the hypothesis that the development and function of the adrenal cortex could be abnormal in an experimental model of CDH. METHODS: Pregnant rats were exposed on day 9.5 of gestation to 100 mg of 2-4-dichlorophenyl-p-nitrophenyl ether (nitrofen) diluted in olive oil. The sham group was treated only with oil. Fetuses were recovered on the 21st day, bled, and examined for the presence or absence of CDH. Adrenal glands from sham and CDH animals were dissected, weighed, and prepared for histologic, biochemical, and immunohistochemical studies (ki-67) aimed at measuring total DNA, total protein, and the proportion of proliferating cells. Serum corticosterone levels were assayed. The results in both groups were compared with parametric tests with a significance level of P <.05. RESULTS: The adrenal weight was not different in CDH animals versus controls (0.049 +/- 0.014 v 0.052 +/- 0.012% of body weight; not significant). Total DNA was reduced significantly (1.180 +/- 0.481 v 1.909 +/- 0.893 microgram P <.05) with unchanged DNA to protein ratio. Proliferation index in both groups was 20.1 +/- 3.1% and 26.5 +/- 7.5%, respectively (not significant), and the proliferating cells were mainly located in the glomerular areas of the glands. Corticosterone levels were similar in both groups. CONCLUSIONS: Nitrofen induces very slight changes in the development of adrenal glands of fetal rats, expressed by reduced cell proliferation especially in glomerular areas, reduced total DNA with preservation of cell sizes (constant DNA to protein ratio), with no change in function because corticosterone levels remained unchanged. It is doubtful that primary adrenal malformation/malfunction contributes to the severity of CDH in this model.

Adrenal Cortex↗
PubMed2001

Neural crest-derived defects in experimental congenital diaphragmatic hernia.

Congenital diaphragmatic hernia (CDH) is often associated with other malformations. This study tests the hypothesis that the heart and great vessels, thymus, parathyroids, and thyroid might be abnormal in the rat model of CDH as a result of disturbed neural-crest development. Time-mated pregnant rats were fed either 100 mg 2-4-dichlorophenyl-p-nitrophenyl ether (nitrofen) or vehicle on gestational day 9.5. Diaphragm, lung, heart, and thymic malformations were sought after dissection and the parathyroids and thyroid were histologically investigated in term fetuses. Ten control fetuses had no malformations, whereas 22 of 32 nitrofen fetuses had CDH and 20 had cardiovascular defects like narrow pulmonary outflow tract (n = 7), aberrant right subclavian artery (n = 7), ventricular septal defect (n = 4), atrial septal defect (n = 4), tetralogy of Fallot (n = 2), double-outflow right ventricle (n = 2), right ductus arteriosus (n = 2), and others. The thymus was present but was significantly hypoplastic in all nitrofen fetuses and was ectopic or single-lobed in 28% of them while the parathyroid glands were unilaterally absent or ectopic in 50%. The thyroid was only minimally malformed or ectopic. In conclusion, malformations of structures derived from the pharyngeal arches are likely neural-crest related in rats exposed to nitrofen.

Animals↗
PubMed2000

Neural crest-derived defects in experimental esophageal atresia.

Esophageal atresia (EA) is often associated with cardiovascular and other malformations that are likely neural crest derived. The present study tests the hypothesis that the heart and great vessels and the thymus and parathyroids may be abnormal in the rat model of EA as a result of disturbed neural crest development. Time-mated pregnant rats received intraperitoneally on d 8 and 9 of gestation either 2 mg/kg adriamycin or vehicle. Esophageal, heart, and thymic malformations were sought under the microscope in term fetuses. The parathyroids were histologically investigated. Control fetuses had no malformations, whereas 69 of 109 fetuses exposed to adriamycin had EA and 45 of 69 had 15 right aortic arches, nine aberrant right subclavia, eight ventricular septal defects, six narrow pulmonary outflow tracts, five tetralogies of Fallot, three double outflow right ventricles, three double aortic arches, three atrial septal defects, three right ductus arteriosus, and two truncus. The thymus was absent in 19, hypoplastic in 12, and ectopic in five out of 36 fetuses with EA in which it was studied, whereas the parathyroid glands were absent in 16, single in four, and ectopic in one of the 23 fetuses with EA in which they were studied. In conclusion, the nature of the cardiovascular, thymic, and parathyroid malformations associated with EA in rats is consistent with the hypothesis of neural crest participation in their pathogenesis. Mechanisms simultaneously disturbing foregut septation, somitic segmentation, and neural crest development should be sought to explain the combined occurrence of malformations in EA.

Animals↗
PubMed1999

Cardiovascular malformations in congenital diaphragmatic hernia: human and experimental studies.

BACKGROUND/PURPOSE: Cardiovascular malformations (CVM) associated with congenital diaphragmatic hernia (CDH) account in part for the high mortality caused by this defect. The aim of this study is to examine the nature of these malformations in a large series of autopsies and to assess if similar defects are also present in rat fetuses with experimental CDH. METHODS: The incidence of CVM and their nature were examined in the autopsy records of 136 stillborns and neonates with CDH admitted to our institution in the last 30 years. Experimental CDH was induced in rat fetuses by giving 100 mg of nitrofen to their mothers on gestational day 9.5, and the fetuses were harvested on day 21 (near full term). The presence of CDH and the anatomy of the heart and great vessels were studied under dissecting microscope after formalin fixation. Unexposed fetuses were used as controls. RESULTS: Thirty-three newborns with CDH (24%) had CVM, either isolated or associated with other defects, and 7 had heart hypoplasia. Most CVM (ventricular septal defect, tetralogy of Fallot, transposition of the great vessels, double-outlet right ventricle) involved the outflow tract. In our animal experiments, no malformations were found in 21 control pups. Conversely, 80 of 130 nitrofen-exposed fetuses (61%) had CDH, and 59 of them (74%) had CVM. A significant association (Fisher's Exact test, P<.01) was found between CDH and CVM because only 25 of the 50 exposed animals without CDH (50%) had CVM. Again, most defects involved the outflow tract and were similar to those seen in human CDH (tetralogy of Fallot, persistent truncus, ventricular septal defect, double-outlet right ventricle, aberrant right subclavian artery, agenetic ductus, and interrupted aortic arch). Animals with CDH had significantly decreased heart weight to fetal weight ratio in comparison with controls and with those without CDH. CONCLUSIONS: The similar nature of the cardiovascular defects found in babies succumbing to CDH and in nitrofen-exposed rats suggests that a similar disturbance of the regional organogenesis related to the neural crest might be involved in both settings, and further validates the use of this animal model for clarifying the cellular and molecular pathogenetic mechanisms.

Animals↗
PubMed1999

Skeletal malformations associated with esophageal atresia: clinical and experimental studies.

BACKGROUND/PURPOSE: Patients with esophageal atresia (EA) often have skeletal malformations. The purpose of this study is to examine if similar defects occur in rat fetuses prenatally exposed to Adriamycin, a chemical capable of causing EA in these animals. METHODS: The charts of 443 babies with EA were reviewed to assess the incidence and nature of these defects in them. Time-mated female rats were given either 2 mg/kg intraperitoneal Adriamycin (experimental group, n = 16) or no treatment (control group, n = 4) on gestational days 8 and 9, and the fetuses were removed near term. Skeletal anatomy was studied after alcian blue and alizarin red staining. RESULTS: A total of 528 skeletal malformations, mainly abnormal segmentation and vertebral identity (extra or defective bodies or ribs), mishaped vertebral bodies, and limb malformations like radial aplasia or hypoplasia were found in 245 babies (55%). Costal fusion and sternal anomalies were present in 17 and 4 babies, respectively. In the animal study, all control fetuses were normal, whereas 83 of 134 experimental fetuses (62%) had EA accompanied by other malformations. No segmentation or vertebral identity anomalies were seen, but butterfly, wedged, and asymmetric vertebral bodies were found at various levels in all animals with EA and in about half of those without it. Three fetuses had rib anomalies, and 3 more had sternal malformations. Ossification of limbs was delayed in treated fetuses and short, thick, and crooked bones were seen in 4 of 31 fetuses with EA and in none of the Adriamycin-exposed ones without EA. CONCLUSIONS: Adriamycin exposure induces in fetal rats, in addition to esophageal, duodenal, and anorectal atresias, high proportions of vertebral malformations and some limb defects of nature not identical but quite similar to that of babies with EA. This further validates this model for investigating the nature of the processes leading to EA and its associated malformations.

Animals↗
PubMed1996

Experimental ureterohydronephrosis in fetal rats.

This study tests the hypothesis that prenatal exposure to 2,4-dichlorophenyl-p-nitrophenyl ether (nitrofen), an herbicide known to induce pulmonary hypoplasia and other malformations in fetal rats, also may induce ureterohydronephrosis (UHN) and oligohydramnios. Time-dated pregnant Wistar rats were given 100 mg of the chemical on day 9 or 11 of gestation, and the findings in their fetuses were compared with those of suitable controls. Marked bilateral UHN was found in the majority of exposed fetuses, but without evidence of either mechanical obstruction or dysplastic parenchymal lesions. These animals had various degrees of lung hypoplasia. The amount of fluid in their amniotic sacs was increased rather than decreased and it was independent of lung weight but correlated to some extent with UHN grade. Urinary tract dilatation and polyhydramnios in this model most likely are attributable to polyuria caused by nitrofen-induced impairment of renal concentrating capacity. This relatively simple animal model might facilitate research into some aspects of the physiology of nonobstructive, prenatally dilated urinary tracts.

Animals↗
PubMed1995

Prenatal growth of the human mandibular condylar cartilage.

The question of whether the condylar cartilage possesses a growth potential like that of the long bone growth plates has been the subject of contrasting viewpoints. We have recently established that the thickness of the human tibial growth plate progressively decreases during the second half of the fetal period, but that the changes in the total human condylar thickness do not correlate with fetal age or weight. The present study examined the change in the thickness of the human mandibular condyle layers during the fetal growth of the mandible. Mandibles were obtained from autopsy of 19 human fetuses ranging in fetal age from 18 to 41 weeks. The total length of the mandible, the lengths of the mandibular body and of the ramus were measured, as well as the gonial angles. The total thickness of the condyle, and the thickness of the articular, progenitor, cartilage, chondroblast, and hypertrophic chondrocyte layers were measured on the central segment of central sagittal sections of the mandibular condylar cartilage. The total mandible, the corpus and the ramus lengths increased linearly with the age of the fetus and they all correlated strongly with fetal weight. However, changes in the total condylar thickness and in the thickness of the cartilage layer (chondroblast plus hypertrophic chondrocytes) did not correlate with fetal weight or mandibular length. The thickness of the articular layer increased with weight, but changes in the progenitor layer were independent of corporal and mandibular growth.(ABSTRACT TRUNCATED AT 250 WORDS)

Cartilage, Articular↗
PubMed1994

Detection of delta F508 cystic fibrosis mutation by polymerase chain reaction from old paraffin-embedded tissues: a retrospective autopsy study.

This study analyzes the usefulness of the polymerase chain reaction technique in the detection of delta F508 mutation in 11- to 25-yr-old formalin-fixed paraffin-embedded tissues obtained from the autopsy of 38 cystic fibrosis patients (nine with meconium ileus). Two different pairs of oligonucleotide primers were used: C16 B/C16 D that amplify 98 and/or 95 bp and FQ1/FQ2 that amplify 50 and/or 47 bp. After two independent rounds of polymerase chain reactions with the two sets of primers, amplification products were obtained in 67.5% of the cases when using C16 B/C16 D primers and in all cases when using FQ1/FQ2 primers. Fifty percent of the chromosomes analyzed in the 29 patients without meconium ileus had the delta F508 mutation, which was present in 13 heterozygous and 8 homozygous patients. The remaining eight cystic fibrosis patients did not carry that mutation. These results are similar to those reported in cystic fibrosis patients from Spain. In the meconium ileus group, we found a higher than expected proportion of delta F508 mutation; all patients showed the delta F508 mutation in at least one chromosome, seven patients (77.8%) being homozygous and two (22.2%) heterozygous. Present results indicate that delta F508 mutation can be detected by polymerase chain reaction in old paraffin-embedded tissues when appropriate primers are used.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1992

Human growth plate development in the fetal and neonatal period.

The development of the normal human upper tibial growth plate was studied at autopsy in 46 stillborns and 79 newborns of 20-41 weeks gestational age. During this time period, the histology of this plate evolves from a highly cellular structure with relatively poor columnar organization and matrix development to the well known structure seen later in postnatal life. The thickness of the growth plate, assessed in the area surrounding the longitudinal tibial axis, decreases continuously from 1.15 mm on the 20th week to 0.6 mm on the 38th week. This decrease results from losses of both matrix and cellular components, mostly of the latter. However, the relative fraction of area occupied by the matrix significantly increased (12%) and matrix area per cell increased 1.5 times over the last half of gestation, indicating a maturation process of the plate towards a more matrix-oriented structure with age. In this maturation process the number of cells per unit area does not change and the average size of the cells appears to decrease. Plate thickness does not decrease further in the final 3 weeks of pregnancy and increases in early neonatal life; this has no apparent influence on the tibial growth rate. In the period under study the relative anatomical participation of the upper tibial growth plate decreases from approximately 4% of the radiographic length of the tibia on the 20th week to less than 1% at term. Present data will provide fetal and neonatal growth plate standards needed to obtain a better understanding of this structure during both normal and abnormal conditions.

Bone Matrix↗
PubMed1991

Histiocytic cytophagic panniculitis: report of a case in a 12-year-old girl.

We report a 12-year-old girl with nodular skin lesions, fever, pancytopenia, coagulation defects and a fatal outcome within 4 months. Histopathology revealed proliferation of histiocytes with haemophagocytosis in skin, perivisceral fat and haemopoietic organs. The symptoms were most consistent with cytophagic histiocytic panniculitis.

Blood Coagulation Disorders↗
PubMed1990

Extrinsic fetal akinesia and skeletal development: a study in oligohydramnios sequence.

Long-bone morphometry and cephalometry were performed in 13 newborns with oligohydramnios sequence (OS) in order to establish whether or not skeletal changes existed in extrinsic fetal akinesia similar to those observed in the fetal akinesia deformative sequence (FADS) (i.e., hypoplastic long bones and micrognathia). Oligohydramnios sequence was caused by bilateral renal agenesis in five cases and obstructive uropathy in eight cases. Twenty-one stillborns and newborns who had died from conditions other than renal anomalies or congenital malformations were used as controls. Normal longitudinal and periosteal long-bone growth and absence of micrognathia were found in OS patients. Skeletal differences between FADS and OS may be explained not only by timing, duration, and degree of reduced motility but also, and more importantly, by the normal muscular stress in OS patients.

Amniotic Fluid↗
PubMed1985

Radiation-induced osteochondroma-like lesion in young rat radius.

To investigate the effects of radiation on the perichondrial groove of Ranvier in osteochondroma development, the external surface of the distal growth plate of the radius in both forelimbs of 30 ten-day-old rats was exposed to a single low dose of radiation (150 r), which was focused on the perichondrial groove. This induced the formation of a chondrocyte nest at the proximal external edge of the growth plate (five to nine days after irradiation). With advancing longitudinal growth of the bone, the chondrocyte nest occupied a diaphyseal position. At nine to 11 days the chondrocyte nest underwent endochondral ossification. At 13-15 days, this osteochondroma-like lesion began to regress with the disappearance of the chondrocyte nest. After 19-21 days, only an irregularly thickened cortical bone remains at the osteochondroma site. Although the possible role of the growth plate subjacent to the irradiated perichondrial groove must be taken into account, the continuity between the perichondrial groove and the osteochondroma, which is separated from the growth plate by the periosteal ring (bone bark), suggests that the perichondrial groove was involved in osteochondroma-like lesion development.

Animals↗