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Biomedical subjects

M J Mahoney

Publications and source records attributed to M J Mahoney.

At least 145 records · Page 8Linked to original sources
PubMed1978

Application of endonuclease mapping to the analysis and prenatal diagnosis of thalassemias caused by globin-gene deletion.

We applied a recently developed and more direct technic to diagnose thalassemia syndromes associated with deletion of particular globin structural genes and to assess a fetus at risk for one of those conditions, deltabeta-thalassemia. The method allows assessment of the globin genes present in total cellular DNA and is applicable to amniotic-fluid cell DNA. Cellular DNA fragments produced by cleavage using two specific restriction endonucleases are separated on the basis of size by agarose-gel electrophoresis, and the distribution of specific sequences among the DNA fragments determined by molecular hybridization. We observed the total deletion of alpha-globin genes in homozygous alpha-thalassemia (hydrops fetalis with hemoglobin Bart's) and the deletion of particular beta and beta-like sequences in cases homozygous for hereditary persistence of fetal hemoglobin and deltabeta-thalassemia. Analysis of amniotic-fluid cell DNA from a fetus at risk for deltabeta-thalassemia demonstrated the feasibility of these improved methods for antenatal diagnosis. The molecular studies confirmed the diagnosis predicted by analysis of fetal blood and established at birth.

Adult↗
PubMed1978

A case of short rib polydactyly.

A patient with neonatal dwarfism had many characteristics of the Majewski syndrome, except for a cleft lip and abnormalities of internal organs. Absence of these anomalies and presence of more severe pathological changes in bone suggest either a wider spectrum for this disorder or a separate entity.

Dwarfism↗
PubMed1978

Applying behavioral methods to nutritional counseling.

A brief survey of what appear to be the most effective and promising techniques of human behavioral change, as applied to nutritional counseling, is presented. Three critical environments of the patient require assessment and intervention: (a) The physical environment, or the physical setting in which the patient functions; (b) the social environment, or other people with whom the patient comes in contact; and (c) the private environment which consists of thoughts, emotions, and basic physiologic systems. Specific assessment and treatment procedures to effect change in each of these environments are outlined, and some suggestions are made concerning the appropriate use of self-help materials.

Behavior Therapy↗
PubMed1977

Prenatal diagnosis of Duchenne's muscular dystrophy.

Two pregnancies at risk for X-linked recessive Duchenne's muscular dystrophy were studied at 18 and 20 weeks. Fetal blood was obtained by placental aspiration for measurement of plasma creatine phosphokinase activity. Activity in the first fetus was 96 IU per liter, as compared to a control range of 0 to 150 IU per liter in 16 pregnancies not at risk for the disorder. The pregnancy continued, and the infant was normal after birth. In the second fetus creatine phosphokinase activity was significantly elevated to 540 IU per liter (P less than 0.001). Fetal blood also showed considerable hemolysis, an unusual observation in placental blood sampling. After abortion, examination of fetal muscle by light, phase and electron microscopy showed characteristic features of Duchenne's muscular dystrophy, including wide variation in muscle-fiber diameter and reduction in the number of fibers per fasciculus. These cases illustrate the potential usefulness of fetal plasma for prenatal diagnosis and, specifically, of creatine phosphokinase activity for diagnosis of muscular dystrophy.

Creatine Kinase↗
PubMed1977

Fetoscopy in continuing pregnancies.

A total of 34 fetoscopic procedures were performed in 28 patients whose fetuses were at risk for hemoglobinopathies (22 cases) or short-limbed dwarfism (three cases). An adequate sample of fetal blood for study of globin-chain synthesis was obtained in 23 of the 25 cases (92%), and valuable diagnostic information was obtained in all three cases at risk for an anomalous fetus. Six patients elected to terminate their pregnancies based on the studies, and in the 22 patients continuing their pregnancies there have been no losses. Thus far, data from this series suggest that fetoscopy is associated with low maternal and fetal morbidity.

Dwarfism↗
PubMed1977

Study of factors causing excess protoporphyrin accumulation in cultured skin fibroblasts from patients with protoporphyria.

The activity of heme synthetase, which catalyzes the chelation of ferrous iron to protoporphyrin to form heme, is deficient in sonicates of skin fibroblasts cultured from patients with protoporphyria. During culture in Eagle's medium supplemented with fetal calf serum, these cells do not accumulate protoporphyrin, however. This may be due to a minimal requirement for heme synthesis, since glycine is incorporated into heme at a low rate which is similar to that in normal fibroblasts. In addition, the activity of delta-aminolevulinic acid (ALA) synthetase, the first and rate-limiting enzyme of heme biosynthesis which catalyzes the formation of ALA from glycine, is normal in lysates of the fibroblasts. Cultured fibroblasts were therefore incubated with ALA in order to bypass the rate-limiting step of heme biosynthesis. In the presence of 25 muM iron, protoporphyrin was detected in protoporphyria cell lines when the concentration of ALA in the medium reached 50 muM, but not in normal lines. As the concentration of ALA was increased above 50 muM, all lines accumulated protoporphyrin. However, the amount was 2-3 times more in cultured fibroblasts from patients with protoporphyria, reflecting their deficiency of heme synthetase activity. When iron was not added to the medium, protoporphyrin accumulated to a similar degree in normal and protoporphyria fibroblasts; this was significantly more than that in the presence of iron. These studies indicate that excessive protoporphyrin accumulation in protoporphyria, which is due principally to deficient heme synthetase activity, may be modified by the rate of ALA formation in heme-producing tissues, and by the availability of iron.

Carbon Radioisotopes↗
PubMed1977

The unborn child.

Explore the source record for details and available documents.

Ethics, Medical↗
PubMed1976

Prenatal diagnosis of hemoglobinopathies. A review of 15 cases.

We attempted prenatal diagnosis of hemoglobinopathies in 15 cases--11 for beta-thalassemia and four for sickle-cell disease. Fetoscopy was used in seven cases, and placental aspiration in eight. One premature labor, with fetal loss, followed placental aspiration. Globin synthesis was assessed by incubation of samples with 3H-leucine and chain separation on carboxymethylcellulose columns. Homozygous disease was predicted in two pregnancies, which were interrupted, and the diagnosis confirmed. In one case homozygosity was suspected. A repeat test was advised but not accepted. The fetus had thalassemia trait. One pregnancy was interrupted despite our prediction of thalassemia trait. Eight pregnancies went to term. Seven predictions that the infants would not have homozygous disease were confirmed. One prediction of sickle trait proved to be sickle-cell disease. Although prenatal diagnosis of hemoglobinopathies is feasible, the present frequency of fetal loss and diagnostic error indicates need for improvement.

Anemia, Sickle Cell↗
PubMed1976

Rapid prenatal and postnatal detection of inborn errors of propionate, methylmalonate, and cobalamin metabolism: a sensitive assay using cultured cells.

A sensitive, reliable, and easily performed procedure is described for the prenatal and postnatal detection of inborn errors of propionate, methylmalonate, and cobalamin metabolism using cultured amniotic cells and skin fibroblasts. With this assay, control fibroblast lines incorporated a mean of 6.89 nanoatoms 14C/mg protein from [1-14C]propionate into trichloroacetic acid (TCA)-precipitable cell material in 10 h. Twenty-five mutant fibroblast lines from patients with propionicacidemia or one of the methylmalonicacidemias fixed 0.04 to 0.93 nanoatoms 14C/mg. Considerable variation was observed, both among and within discrete mutant classes, with respect to the residual amount of propionate pathway activity, possibly reflecting further molecular heterogeneity in these disorders. We applied this procedure to cultured amniotic cells from controls and 4 midtrimester pregnancies at risk for methylmalonicacidemia and diagnosed one fetus with a methylmalonyl CoA apomutase defect and 3 fetuses which were unaffected.

Amino Acid Metabolism, Inborn Errors↗
PubMed1976

Inheritance in protoporphyria. Comparison of haem synthetase activity in skin fibroblasts with clinical features.

The activity of haem synthetase, the enzyme which chelates iron to protoporphyrin to form haem, was measured in cultured skin fibroblasts of children with protoporphyria and their parents from three families. In each family, one parent had deficient haem synthetase activity (3-0-11-1 pmol protohaem formed/mg protein/h) when compared to values in eight non-porphyric controls (means 24-9, range 13-7-51-5). The level of activity in the three parents was similar to that in their affected children. In two families the parent with deficient activity was also thought to be the carrier of the abnormal gene, as judged from a history of photosensitivity and analysis of erythrocyte protoporphyrin concentrations, but in the third family the pattern of inheritance could not be determined from these criteria. The activity of delta-aminolaevulinic acid synthetase was normal in cultured fibroblasts from the protoporphyric children and their parents, excluding a generalised defect in haem-pathway enzymes. These results support the premise that deficient haem synthetase activity, inherited in an autosomal dominant patter, is the primary defect in protoporphyria.

Adolescent↗