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Biomedical subjects

R L Ladda

Publications and source records attributed to R L Ladda.

At least 19 recordsLinked to original sources
PubMed1992

Cutaneous scar at anterior hair line in mother and child with associated frontal bone defect in child.

A large frontal bone defect underlying a "V" shaped scar was noted in a newborn male whose mother had an identical "V" shaped scar at the same location in the anterior hairline. Both had hypertelorism and short palpebral fissures. The mother had no radiographic evidence of skull defect and neither mother nor child had other cutaneous or skeletal anomalies. Cranioplasty was performed on the child using the remaining frontal bones with an excellent cosmetic result. Biopsy performed at operation documented scar tissue extending through the dermis and underlain by thickened dura. Mother and child appear to have a variant form of aplasia cutis congenita, an autosomal dominant trait with wide variation in expression.

Abnormalities, Multiple↗
PubMed1992

The frequency of uniparental disomy in Prader-Willi syndrome. Implications for molecular diagnosis.

BACKGROUND: Prader-Willi syndrome is a genetic disorder characterized by infantile hypotonia, obesity, hypogonadism, and mental retardation, but it is difficult to diagnose clinically in infants and young children. In about two thirds of patients, a cytogenetically visible deletion can be detected in the paternally derived chromosome 15 (15q11q13). Recently, patients with Prader-Willi syndrome have been described who do not have the cytogenetic deletion but instead have two copies of the 15q11q13 region that are inherited from the mother (with none inherited from the father). This unusual form of inheritance is known as maternal uniparental disomy. Using molecular genetic techniques, we sought to determine the frequency of uniparental disomy in Prader-Willi syndrome. METHODS: We performed molecular analyses using DNA markers within 15q11q13 and elsewhere on chromosome 15 in 30 patients with Prader-Willi syndrome who had no cytogenetically visible deletion. We also studied their parents. Three patients with Prader-Willi syndrome who had a cytogenetic deletion served as controls. RESULTS: In 18 of the 30 patients without a cytogenetic deletion (60 percent), we demonstrated the presence of maternal uniparental disomy for chromosome 15 and its association with advanced maternal age. In another eight patients (27 percent), we identified large molecular deletions. The remaining four patients (13 percent) had evidence of normal biparental inheritance for chromosome 15; three of these patients were the only ones in the study who had some atypical clinical features. CONCLUSIONS: In about 20 percent of all cases, Prader-Willi syndrome results from the inheritance of both copies of chromosome 15 from the mother (maternal uniparental disomy). With the combined use of cytogenetic and molecular techniques, the genetic basis of Prader-Willi syndrome can be identified in up to 95 percent of patients.

Adult↗
PubMed1991

Cerebro-ocular dysplasia--muscular dystrophy (Walker Warburg) syndrome. Findings in 20-week-old fetus.

A 20-week fetus affected with cerebro-ocular dysplasia and muscular dystrophy (Walker-Warburg Syndrome) is reported. The central nervous system (CNS) findings were typical of those previously described in this disorder, and were characterized by lissencephaly, hydrocephalus, and cerebral and cerebellar cortical dysplasia with glial and neuronal displacement into the leptomeninges. In addition, severe hypoplasia of pyramidal tracts were noted in the brain stem and spinal cord, as well as malformation of the inferior olivary and dentate nuclei. Skeletal muscle and eyes appeared normal on light microscopy. The genetic defect in this disorder is expressed in the CNS early during the first trimester and causes a marked disorder of cellular migration. Overt changes in muscle occur during a later period. The changes in the CNS are similar to, but more severe than, those found in Fukuyama congenital muscular dystrophy, and both may represent a failure of constraint of neuronal migration. Whether the syndromes characterized by cerebro-ocular dysplasia and muscular dystrophy are genetically heterogeneous or allelic variations is unknown. Molecular genetic analysis should elucidate this question.

Brain↗
PubMed1990

Neurologic manifestations in 18q- syndrome.

We report a mother and son with a deletion at 18q22.3. Both have the typical manifestations of the 18q- syndrome. In addition, both have an action tremor which became apparent in childhood. The mother subsequently developed chorea and dysmetria in late adolescence. Magnetic resonance imaging of their brains showed poor myelination of the central white matter tracts with relatively normal myelination of the corpus callosum. We propose that these neurologic findings are most likely due to a failure of expression of the myelin basic protein gene.

Abnormalities, Multiple↗
PubMed1990

Five children with del (2)(q31q33) and one individual with dup (2)(q31q33) from a single family: review of brain, cardiac, and limb malformations.

Five matings to a dir ins (6;2)(q16;q31q33) carrier have produced a high frequency (42%) of offspring with unbalanced karyotypes. Five children have the derivative chromosome 2 resulting in del (2)(q31q33) and one individual received the derivative chromosome 6 leading to dup (2)(q31q33). The findings associated with the deletion include pre- and postnatal growth retardation, developmental delay, minor facial anomalies, seizures, complex structural heart defects, and limb deficiency. Autopsy of one individual showed complex brain malformations including hydrocephalus secondary to obstruction of the foramina of Monro, extensive heterotopias and polymicrogyria, and an unusual form of total anomalous pulmonary venous return. We compare the findings in these children to those of previously reported cases and construct an overview of the range of anomalies. Apparently, no other individual with dup (2)(q31q33) has been described. We compare the physical peculiarities of our patient with those of individuals with duplications of overlapping regions of 2q.

Abnormalities, Multiple↗
PubMed1990

Dexamethasone receptor levels in palatal and lung fibroblasts of adult A/J and C57BL/6J mice: relationship to glucocorticoid-induced cleft palate.

Glucocorticoid-induced cleft palate (CP) has been used as an animal model for hormonal teratogenesis. In mice, the susceptibility to glucocorticoid-induced CP varies with the strain, A/J being very sensitive and C57/BL6J relatively resistant. Studies in adult and embryonic murine tissues have attempted to correlate the number of glucocorticoid receptors and CP susceptibility, with conflicting results. The relative quantities of dexamethasone receptors were now studied in established palatal and lung fibroblast cell cultures obtained from adult C57 and A/J mice. A rapidly saturable, stable binding system was demonstrated. Scatchard plots were linear indicating a single class of high affinity receptors. The glucocorticoid receptor number ranged from 6.2 x 10(-16) mole/microgram prot to 8.6 x 10(-16) mole/microgram prot, while the KD varied from 1.0 x 10(-8) M to 2.8 x 10(-8) M. The differences in receptor characteristics between murine strains were not significant (p greater than 0.05). The absence of a difference in receptor number between the two strains may reflect the limitation of fibroblast cell culture in assessing glucocorticoid binding in vivo. Alternatively, if a difference in palatal dexamethasone receptor levels between mice strains exists, it may occur only in the embryo.

Animals↗
PubMed1990

"Marden-Walker syndrome": neuropathologic findings in two siblings.

Neuropathologic examination of two siblings with phenotypic features consistent with Marden-Walker syndrome revealed central nervous system abnormalities which include reduction in the number of spinal anterior horn cells. The occurrence of these changes in a sibling pair provides strong evidence for a genetic etiology. The relationship between the neuropathologic changes and other phenotypic manifestations in this syndrome and in the closely related syndrome of Pena-Shokeir are discussed.

Abnormalities, Multiple↗
PubMed1990

Inheritance of an RNA splicing mutation (G+ 1 IVS20) in the type III procollagen gene (COL3A1) in a family having aortic aneurysms and easy bruisability: phenotypic overlap between familial arterial aneurysms and Ehlers-Danlos syndrome type IV.

Inheritance of a single base mutation in the type III procollagen gene (COL3A1) was studied in a family with aortic aneurysms and easy bruisability. The mutation was a substitution of A for G+ 1 of intron 20 of the gene and caused aberrant splicing of RNA transcribed from the mutated allele. The phenotype in the family included aortic aneurysms that ruptured and produced death. It also included easy bruisability, but it did not include other characteristic features of Ehlers-Danlos syndrome type IV, such as ecchymoses, abnormal scarring, or prominent subcutaneous blood vessels. The data from the family, together with a review of other probands with mutations in the type III procollagen gene, indicated that there is phenotypic overlap between Ehlers-Danlos syndrome type IV and familial arterial aneurysms not associated with any overlap between Ehlers-Danlos syndrome type IV and familial arterial aneurysms not associated with any of the striking changes in skin originally cited as a characteristic feature of Ehlers-Danlos syndrome type IV. In addition, the results suggested that DNA tests for mutations in the type III procollagen gene may be useful to identify individuals predisposed to developing arterial aneurysms.

Adult↗
PubMed1989

A review of phenotype-karyotype correlations in individuals with interstitial deletions of the long arm of chromosome 2.

We report an infant with del(2)(q31q33). His phenotype is compared with those of the 7 children reported previously with the apparently identical deletion. Nine cases of deletions involving other segments of chromosome 2q are reviewed. Common manifestations of the 2 groups include small size at birth, growth and developmental retardation, cardiovascular malformation, microcephaly, and cleft palate.

Abnormalities, Multiple↗
PubMed1989

Prenatal detection of Roberts-SC phocomelia syndrome: report of 2 sibs with characteristic manifestations.

We describe 2 sibs with Roberts-SC phocomelia syndrome. Although an ultrasound scan performed at 13 weeks of gestation failed to identify specific abnormalities, repeat scan at 17 weeks detected tetraphocomelia. Ultrasonography can reliably detect Roberts-SC phocomelia prenatally; however, serial scans may be needed. Postmortem examination of the proposita confirmed the sonographic findings and also disclosed dysplastic kidneys and ovarian dysgenesis. The degree of phenotypic variation observed between the sibs supports the hypothesis that Roberts syndrome and SC phocomelia represent a single genetic entity.

Abnormalities, Multiple↗
PubMed1989

Humero-radial synostosis with ulnar defects in sibs.

Sibs with virtually identical humero-radial synostosis (HRS) are presented and compared with 17 previously reported cases from the literature of recessively transmitted HRS. The range of anomalies described includes (in addition to humero-radial synostosis) ulnar hypoplasia, patellar hypoplasia, and chronic glomerulo-nephritis.

Abnormalities, Multiple↗
PubMed1987

Induction and suppression of type I collagenase in cultured human cells.

A number of peptide growth factors have been shown to induce the secretion of type I collagenase into the medium of human fibroblast cultures (Chua et al., 1985). In this study the ability of eye-derived growth factor, lectin and tumor-promoting agents on collagenase induction in human fibroblast cells were examined. These agents were found to be able to induce collagenase production to a similar extent as epidermal growth factor. Dexamethasone at 10-100 nM was found to suppress collagenase induction in human fibroblast cells. The cell-type specificity of this enzyme induction by growth factors was studied by using a human epidermoid carcinoma cell line, A-431. An Mr 55,000 band appeared in the medium of A-431 cells upon 22 h exposure to EGF. Two-dimensional peptide pattern of the Mr 55,000 band in A-431 cells was identical to the counterpart in HF cells. Our results indicated that the induction of collagenase was not unique to human fibroblast cultures.

Carcinoma, Squamous Cell↗
PubMed1987

Effect of tunicamycin on the biosynthesis of human fibroblast collagenase.

It is generally accepted that collagenase from human fibroblast cultures consists of two proenzymes (Mr 60,000 and 55,000) and two active forms (Mr 50,000 and 43,000). We demonstrated previously that epidermal growth factor (EGF) as well as a number of other growth factors induced the secretion of procollagenase (Mr 60,000, Mr 55,000) into the medium of human fibroblast cultures (Chua et al., 1985). In the presence of tunicamycin and EGF, the secretion of the larger form of procollagenase was suppressed preferentially with concomitant appearance of a new band, Mr 40,000. This Mr 40,000 band could be specifically immunoprecipitated by antibody raised against human collagenase. By two-dimensional peptide mapping, the Mr 40,000 material appeared to have similar composition as the Mr 60,000 band. In a time course study, the Mr 55,000 procollagenase band was the earliest protein to appear in the medium after 1 hour labeling with [35S]-methionine. The Mr 60,000, 50,000 and 43,000 bands appeared after a 2 hour labeling period. Our results indicate that human collagenases are glycosylated proteins and are synthesized via the dolichol phosphate pathway.

Collagenases↗
PubMed1987

Purkinje cell inclusions and 'atelencephaly' in 13q-chromosomal syndrome.

Severe microcephaly was present from birth in a child with a 13q-chromosomal syndrome [46,XY,del(13)(q22q31)]. He died at 20 months of age. Neuropathologic findings included atelencephaly and eosinophilic cytoplasmic inclusions in cerebellar Purkinje cells. Ultrastructurally, the inclusions consisted of stacks of parallel cisternae separated by electron-dense granular material. The relationship between these inclusions and the smaller cytoplasmic inclusions known as "lamellar bodies" is discussed, and the central nervous system malformations in this syndrome are reviewed.

Chromosome Aberrations↗
PubMed1986

Receptor for epidermal growth factor retains normal structure and function in aging cells.

Cellular responsiveness to epidermal growth factor (EGF) and the structure of the receptor for epidermal growth factor (EGF-R) were compared in young and senescent human fibroblast (HF) cells. Biosynthetic labeling of HF cells with [35S] methionine followed by immunoprecipitation with EGF-R antibody revealed the presence of Mr 170 000 EGF-R in cells from both stages. Autophosphorylation of EGF-R in response to EGF was identical in young and senescent cells. Phosphoamino acid analysis of the autophosphorylated EGF-R indicated that tyrosine residues were phosphorylated in each preparation. Two-dimensional peptide mapping of [125I]EGF-R from young and senescent cells showed essentially the same pattern, indicating that EGF-R does not apparently undergo detectable changes in senescent human fibroblasts. The responsiveness of aging HF cells to EGF for the induction of ornithine decarboxylase activity and for the production of secretory proteins was measured. Young and senescent HF cells showed about a three-fold induction of collagenase activity upon addition of EGF. Ornithine decarboxylase activity was also stimulated by EGF to a comparable level in young and senescent cells. Our results indicate that the responsiveness of HF cells to EGF for these two biochemical parameters does not decline with the loss of proliferative activity.

Amino Acids↗