摘要:

AbstractThe cardiovascular teratogenicity of nimustine hydrochloride (ACNU) was studied in rat fetuses. This drug is a nitrosourea derivative anticancer agent and produces alkylation of DNA. Pregnant Donryu rats were treated with single doses of 10, 11 or 13 mg/kg of the teratogen at various stages during gestation. Examination of the hearts was performed by microdissection after sacrificing the animals on the 20th day of gestation. The highest frequency of cardiovascular anomalies was found in the groups treated on the 8th day of gestation, but there was no difference in the rates induced by the three dosages of ACNU administered. The most common cardiovascular anomalies observed were ventricular septal defect (76.8%) and double outlet right ventricle (10.3%). A considerable number of affected fetuses (37/263) showed complex cardiac anomalies with atrioventricular (AV) malalignment and other AV valve anomalies. These anomalies include: double inlet left ventricle, straddling AV valve, atresia or stenosis of the AV valve, and dysplastic AV valve. ACNU appears to be a useful teratogenic agent for inducing complexes of cardiac anomalies which include AV malalignment.

ISSN:0040-3709    

DOI:10.1002/tera.1420380602

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY

摘要:

AbstractEpidemiological and genetic variables in clefts were analyzed during the years 1978–1986 in a case‐control study of congenital malformations in the Emilia Romagna region of northern Italy. Among 150,168 newborns, 200 cases of cleft were detected, yielding a prevalence of 1.33 per 1,000. These clefts consisted of 112 (0.075%) cases of cleft lip with or without cleft palate (CL±P) and 88 cases (0.058%) of cleft palate (CP). Coexisting abnormalities were found in 32% of cases. The heritability coefficient of CL±P was 0.84. No cluster in time or space could be demonstrated. Epilepsy was the only maternal risk factor found to be correlated with clefts. A predominance of males was found among CL±P

ISSN:0040-3709    

DOI:10.1002/tera.1420380603

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY

摘要:

AbstractMice homozygous for either of two mutations, chondrodysplasia (cho) or cartilage matrix deficiency (emd), have short‐limbed chondrodystrophy. This phenotype includes retroganthia, relative macroglossia, and cleft palate. It has been postulated that the cleft palate in these mice is the result of tongue obstruction during palatogenesis. Agnathia associated with microglossia is an independent spontaneously occurring defect in the strains bearing these mutations. The coincidental occurrence of agnathiamicroglossia with chondrodystrophy lends itself to the study of the mechanism of cleft palate formation. We examined approximate midsagittal histological sections of normal and chondrodystrophic newborn mice, both with and without agnathia. Mandibular measurements and examinations of palate closure and tongue structure were made from photographic prints. Typical chondrodystrophic mutants with cleft palates had a mean mandibular length that was 66% of normal and a tongue that appeared large relative to the shortened mandible. Chondrodystrophic mutants with agnathia and microglossia had a mean mandibular length that was further reduced to 30% of normal, yet had a closed palate. We also observed two nonagnathic chondrodystrophic mutants that had slightly decreased mandibular lengths, microglossia, and closed palates. These observations suggest that tongue obstruction during palatogenesis is the pathogenetic mechanism of cleft palate in chondrodystrophic mice. A similar tongue obstruction hypothesis has been proposed as the mechanism of cleft palate formation in the human Pierre Robin sequence, which consists of retrognathia, glossoptosis, and cleft palate. This mechanistic hypothesis has been challenged, but our findings support the tongue obstruction hypothesis in the Robin clef

ISSN:0040-3709    

DOI:10.1002/tera.1420380604

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY

摘要:

AbstractTheH‐2region of mouse chromosome 17 is known to include one or more genes that affect susceptibility to cortisone‐induced cleft palate. We have now studied congenic strains that possess crossovers in the interval betweenH‐2SandH‐2Dand have observed significant differences in susceptibility among recombinants that had been believed to possess the sameH‐2haplotypes. Pregnant mice were injected on days 11 through 14 of gestation with 100 mg of cortisone per kg of body weight. The frequency of cleft palate in B10.A(2R) was significantly greater than in B10.A(1R), despite the fact that both haveH‐2a/H‐2bcrossovers in the interval between theSandDloci and have the same alleles at all loci that have been previously characterized. Both B10.BAR5 and B10.BAR12 were significantly more susceptible than B10.A(18R), although these strains also share the same alleles at all loci that have been previously characterized. All three of these strains haveH‐2b/H‐2arecombinant chromosomes, with crossovers in theS/Dinterval. Genetic linkage betweenH‐2and the high‐susceptibility gene of B10.BAR5 was confirmed by testingH‐2homozygotes derived by intercrossing backcross animals. These data therefore suggest that a gene coding for susceptibility, which we designateCps‐1, maps in the 350‐kb interval betweenH‐2SandH‐2D, and the congenic strains that we have found to be different have different crossover points within this interval. Alleles at theCps‐1locus have embryonic effects, but no demónstrable e

ISSN:0040-3709    

DOI:10.1002/tera.1420380605

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY

摘要:

AbstractThe severe lethal chondrodystrophies in man result in a common clinical syndrome including shortening of the face, mandible, and limbs. Studies of three lethal chondrodystrophic mutants in mice, viz., chondrodysplasia (cho), cartilage matrix deficiency (cmd), and disproportionate micromelia (Dmm), which share this syndrome, were performed with the aim of identifying histochemical, immunofluorescence, or ultrastructural differences which might exist among these hereditary cartilage disorders: We examined limb cartilage epiphyses from day 18 normal and mutant fetuses and observed repeatable, mostly qualitative differences. All observations were made relative to the normal control. Histochemical staining of matrix proteoglycan was moderately decreased inchoandDmmcartilage and markedly decreased incmdwhen compared to the normal control. Staining of matrix collagen was irregular in distribution incho, increased incmd, and decreased inDmm.Immunofluorescence of proteoglycan was increased in the matrix ofchoandDmmand decreased incmd.Immunofluorescence of type II collagen was heterogeneous and moderately decreased in the matrix ofcho, increased incmd, and markedly decreased inDmm.Immunofluorescence of link protein inchowas localized in the cellular‐pericellular region as in the normal and appeared increased in the matrix ofcmdandDmm.Immunofluorescence of chondronectin was localized in the cellular‐pericellular region and appeared normal in all three mutants. Major differences in cellular and matrix ultrastructure were observed among the mutants, including a decreased frequency of small‐diameter collagen fibrils inchoandDmm, increased density of collagen fibrils incmd, and dilated RER inDmm.These observations demonstrate that distinct structural and possibly molecular differences exist among the chondrodystrophies. In the case ofcmd, the differences correlated with a previously reported molecular defect, viz., absence of core protein of cartilage specific proteoglycan in the cartilage of this mutant. It is anticipated that the methods used in the present study can be applied to humans in case classification and in identifying potential mouse‐human cor

ISSN:0040-3709    

DOI:10.1002/tera.1420380606

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY

ISSN:0040-3709    

DOI:10.1002/tera.1420380607

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY

ISSN:0040-3709    

DOI:10.1002/tera.1420380608

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY

ISSN:0040-3709    

DOI:10.1002/tera.1420380609

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY

ISSN:0040-3709    

DOI:10.1002/tera.1420380610

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY

ISSN:0040-3709    

DOI:10.1002/tera.1420380611

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY