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Biomedical subjects

M Lipson

Publications and source records attributed to M Lipson.

At least 19 recordsLinked to original sources
PubMed2001

Severe lactic acidosis caused by a novel frame-shift mutation in mitochondrial-encoded cytochrome c oxidase subunit II.

We report the first frame-shift truncation mutation in a mitochondrial DNA (mtDNA)-encoded subunit II of cytochrome c oxidase (COXII). The mutation was identified by temporal temperature gradient gel electrophoresis (TTGE) followed by direct DNA sequencing in an infant who died at 12 days of age following a course of apnea, bradycardia, and severe lactic acidosis. The patient had a twin brother who died at two days of age of similar course. The mutation, 8042delAT, produced a truncated protein that was 72 amino acids shorter than the wild type protein. The mutant protein, missing one third of the amino acid residues at the C-terminal essential for hydrophilic interaction with cytochrome c, ligand binding to CuA and Mg, and the formation of proton and water channels, apparently has devastating effects on mitochondrial respiratory function.

Acidosis, Lactic↗
PubMed2001

A5814G mutation in mitochondrial DNA can cause mitochondrial myopathy and cardiomyopathy.

We describe a 5-year-old child with hypertrophic cardiomyopathy, mitochondrial myopathy, and lactic acidosis. Mitochondrial DNA analysis showed a heteroplasmic A5814G point mutation in the tRNA(Cys) gene. The mutational load was extremely high (>95%) in muscle, fibroblasts, and blood. This report expands the clinical heterogeneity of the A5814G mutation, which should be considered in the differential diagnosis of hypertrophic cardiomyopathy in childhood.

Acidosis, Lactic↗
PubMed2000

Novel approach for specific detection of herpes simplex virus type 1 and 2 antibodies and immunoglobulin G and M antibodies.

Recently a few new herpes simplex virus (HSV) type-specific serological diagnostic tests have been introduced to the commercial market, but these tests have some limitations. Moreover, it is not yet clear which commercial test can be regarded as a "gold standard" for the serodiagnosis of HSV infections. In order to improve the clinical diagnostic value of serological tests for the detection of HSV infections, we developed novel, competition-based enzyme-linked immunosorbent assays for the specific determination of HSV type 2 antibodies (SeroHSV2) and HSV type 1 antibodies (SeroHSV1) and two complementary tests for the detection of HSV immunoglobulin M (IgM) and IgG antibodies (SeroHSV IgM and SeroHSV IgG). These four new kits were evaluated in comparison with some commercial kits for the detection of HSV antibodies that are commonly used at present in Israeli clinical laboratories. The results indicate that SeroHSV2 is highly sensitive (>92%) and highly specific (>94%). SeroHSV2 does not cross-react with other alphaherpesvirus antibodies. SeroHSV1 is highly sensitive (>94%) and specific (>91%) compared to four commercial available kits. SeroHSV IgM is highly specific (>92%) in comparison with other commercial HSV IgM tests. The sensitivity of SeroHSV IgM ranges between 50 and 70% compared to these tests. Further investigation of the discrepant results obtained by using in-house competition tests indicated that SeroHSV IgM is more sensitive. SeroHSV IgG was also found to be highly sensitive (>94%) and highly specific (>92%) compared to the other commercial HSV IgG tests.

Antibodies, Viral↗
PubMed1999

Multifocal osteosarcoma following retinoblastoma.

Three survivors of retinoblastoma, one with hereditary bilateral and two with nonhereditary (spontaneous) unilateral disease, developed multifocal osteosarcoma. For one patient, unilateral retinoblastoma was followed by primitive neuroepithelioma at age 13 years. Multifocal chondroblastic osteosarcoma represented the patient's third malignant neoplasm. The course of multifocal osteosarcoma in these three patients compares to that of multifocal osteosarcoma which presents de novo in other patients without prior retinoblastoma.

Adult↗
PubMed1998

Thanatophoric dysplasia type I with syndactyly.

We report on a case of thanatophoric dysplasia type 1 (TD1) due to a Tyr373Cys mutation in the fibroblast growth factor receptor 3 (FGFR3) gene with soft tissue syndactyly of the fingers and toes. Syndactyly has not been previously described in TD or other conditions with FGFR3 mutations, but occurs in several craniosynostosis syndromes due to mutations in FGFR2. We conclude that mutations in FGFR3 may also be associated with developmental abnormalities due to interference with programmed cell death.

Cysteine↗
PubMed1998

Diverse mutations in the gene for cartilage oligomeric matrix protein in the pseudoachondroplasia-multiple epiphyseal dysplasia disease spectrum.

Pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED) are autosomal dominant osteochondrodysplasias that result in mild to severe short-limb dwarfism and early-onset osteoarthrosis. PSACH and some forms of MED result from mutations in the gene for cartilage oligomeric matrix protein (COMP; OMIM 600310 [http://www3.ncbi.nlm. nih.gov:80/htbin-post/Omim/dispmim?600310]). We report the identification of COMP mutations in an additional 14 families with PSACH or MED phenotypes. Mutations predicted to result in single-amino acid deletions or substitutions, all in the region of the COMP gene encoding the calmodulin-like repeat elements, were identified in patients with moderate to severe PSACH. We also identified within this domain a missense mutation that produced MED Fairbank. In two families, one with mild PSACH and the second with a form of MED, we identified different substitutions for a residue in the carboxyl-terminal globular region of COMP. Both the clinical presentations of these two families and the identification of COMP-gene mutations provide evidence of phenotypic overlap between PSACH and MED. These data also reveal a role for the carboxyl-terminal domain in the structure and/or function of COMP.

Achondroplasia↗
PubMed1998

Differential expression of fibroblast growth factor receptors 1 to 4 and ligand genes in late fetal and early postnatal rat lung.

To characterize fibroblast growth factor (FGF) gene expression in the late fetal (days E18 to E22) and early postnatal lung (days P0 to P28), when the alveolar region undergoes extensive growth and reorganization, we analyzed the expression of four FGF receptors and six ligands. FGF receptor 1 (FGFR1) RNA levels were first low (E18) before rising late in the postnatal period (P28). FGFR2 RNA levels were detected early (at E18) and then increased (E20-P0) before falling (P2) to below later postnatal levels (P6 to P28). FGFR3 RNA levels were low at first (E18) and then increased, with peak levels in the days after birth (P2 to P10). FGFR4 RNA levels, barely detected in fetal lung (E18 to E22), increased at birth (P0) and remained high postnatally (P2 to P28). In fetal lung, FGF2 (basic FGF) RNA expression levels were low and FGF1 (acidic FGF) RNA levels were not detected: low RNA levels of each ligand were detected postnatally (P7 to P28). FGF3 to 5 and FGF7 RNA were not detected in fetal or postnatal lung. With in situ hybridization, predominantly the smooth muscle cells of large vessels expressed FGFR1 and 4 mRNA; the epithelial cells of large airways expressed FGFR1, 2, and 4; and alveolar cells expressed FGFR2, 3, and 4. Analysis of protein expression first identified FGF2 localized to the basement membrane of large airways and branching epithelial buds, to mesenchymal cells associated with buds, to the putative smooth muscle cells of large airways and vessels, and to pleural- and mesenchymal-associated cells (E18). Immediately before birth, this pattern of expression persisted (E20 to E22), with FGF2 also being expressed by putative smooth muscle cells of smaller airways and vessels (E22). After birth (P0 to P28), FGF2 expression remained relatively high in the smooth muscle cells of large and small vessels and in pleural cells; in airway smooth muscle cells and in most cells in the alveolar region, however, although FGF2 expression persisted in some cells, its intensity decreased with time.

3T3 Cells↗
PubMed1997

Six patients with oral-facial-digital syndrome IV: the case for heterogeneity.

The oral-facial-digital syndromes (OFDS) have in common minor facial and oral anomalies (including tongue lobulation and/ or hamartomas, accessory frenula, and alveolar anomalies) and variable digital defects such as polydactyly. The classification based on the presence of additional findings [Toriello, 1988, 1993] is not perfect, as many reported examples of a particular OFDS have some other condition. Here we describe six children, all diagnosed as having OFDS IV (OFDS with tibial defects), whose manifestations illustrate the apparent genetic heterogeneity.

Abnormalities, Multiple↗
PubMed1994

Disclosure of diagnosis to children with human immunodeficiency virus or acquired immunodeficiency syndrome.

This paper reviews research and clinical literature relevant to the question of disclosure of diagnosis to children with human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS). The model of pediatric oncology, in which much research already exists, is evaluated for its applicability to HIV and AIDS. Although children seem to benefit from early disclosure of diagnosis of life-threatening illnesses, special cultural and social conditions complicate the question with regard to HIV and AIDS. These conditions include the parent-to-child transmission of HIV and the unique social stigma of having HIV because of its association with homosexuality, drug use, and sexual conduct. The paper presents existing treatment approaches and suggests avenues for further research.

Acquired Immunodeficiency Syndrome↗
PubMed1987

New autosomal dominant branchio-oculo-facial syndrome.

We observed an autosomal dominant disorder of abnormal upper lip, which resembles a poorly repaired cleft lip, malformed nose with broad bridge and flattened tip, lacrimal duct obstruction, malformed ears, and branchial cleft sinuses and/or linear skin lesions behind the ears in several persons in 3 families. In each of the 3 families, an affected parent had at least one affected child. Father-to-son transmission in one of these families ruled out X-linked inheritance. Other anomalies include coloboma, microphthalmia, auricular pits, lip pits, highly arched plate, dental anomalies, and subcutaneous cysts of the scalp. Premature graying of hair occurred in the affected adults. Growth retardation, developmental delay, and hand anomalies are variable components of the syndrome.

Abnormalities, Multiple↗
PubMed1987

Clinical and biochemical variation and family studies in the multiple acyl-CoA dehydrogenation disorders.

We report clinical and biochemical studies in patients with multiple acyl-CoA dehydrogenation disorders (MAD) and their parents. A severely affected (MAD:S) patient presented with neonatal acidosis leading to death and excreted a wide range of straight- and branched-chain acyl CoA derivatives. Two patients with mild variants of the same disorder (MAD:M) presented with neurologic abnormalities, acidotic coma, and/or poor growth; they primarily excreted ethylmalonate and variable amounts of adipate. Fibroblasts from the MAD:S patient demonstrated severely defective radiolabeled substrate oxidation, while the MAD:M cells had milder oxidative defects. Fibroblasts from two other MAD:M and six other MAD:S patients demonstrated analogous defects in substrate oxidation. As a group, MAD:S cells deficient in electron transfer flavoprotein:ubiquinone oxidoreductase had significantly lower residual oxidative activities than did MAD:S cells deficient in electron transfer flavoprotein. Fibroblasts from the parents of four MAD:S patients oxidized radiolabeled substrates significantly less effectively than did normal infant controls but were indistinguishable from normal adult cells. We found relatively higher residual oxidative activities in maternal than in paternal cells. Amniocytes from a fetus at risk for MAD:S catabolized labeled substrates normally; the infant has been clinically and biochemically normal up to 30 months of age.

Acyl-CoA Dehydrogenase↗
PubMed1986

3-Ketothiolase deficiency.

Two patients have been studied in whom the activity of the short chain-length-specific mitochondrial 3-ketothiolase was found to be deficient. Use of a range of 3-ketoacyl-CoA substrates showed that the other 3-ketothiolase isoenzymes were normal in each case. Both patients had episodic ketosis and metabolic acidosis. One patient had substantial evidence of damage to the central nervous system and two siblings who had died of the disease. The organic aciduria was characterized by the excretion of 2-methyl-3-hydroxybutyric acid and tiglyglycine. In one patient the organic aciduria was very subtle and was masked during the presence of ketosis, but it was clarified by an isoleucine load after recovery from ketosis.

3-Hydroxybutyric Acid↗
PubMed1984

Prenatal diagnosis of asphyxiating thoracic dysplasia.

A fetus at risk for asphyxiating thoracic dysplasia was studied with ultrasound examination at 16, 18, and 23 weeks of pregnancy. Definite shortness of fetal femora was observed. Radiographic and histologic examinations after pregnancy termination confirmed the diagnosis. Asphyxiating thoracic dysplasia appears to be one of an increasing number of skeletal dysplasias that can be diagnosed prenatally with ultrasound.

Asphyxia Neonatorum↗