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Biomedical subjects

J A Wolff

Publications and source records attributed to J A Wolff.

At least 109 records · Page 6Linked to original sources
PubMed1987

Expression of retrovirally transduced genes in primary cultures of adult rat hepatocytes.

Differentiated primary rat hepatocyte cultures have been infected with retroviral vectors expressing human hypoxanthine/guanine phosphoribosyltransferase or the transposon Tn5 neomycin-resistance gene. Expression of the markers was detected only after infection of the cells during a short period of cell replication and transient dedifferentiation from days 1 to 5 of culture. Provirus integrated during that period remains fully expressed during the entire subsequent stationary period of culture up to at least 25 days. Selection with the neomycin analogue G418 of cells infected with the neomycin vector led to the appearance of cells with hepatocyte morphology in which newly synthesized albumin was detectable by immunoprecipitation, indicating successful infection of hepatocytes.

Animals↗
PubMed1987

Gene expression from transcriptionally disabled retroviral vectors.

Retroviral vectors are used for the efficient transfer of foreign genes into mammalian cells. We report here the construction of murine retrovirus-based vectors carrying the full-length cDNA for human hypoxanthine phosphoribosyltransferase (HPRT; EC 2.4.2.8) and from which the enhancer sequences, the "CAAT box," and the "TATA box" in the long terminal repeats (LTRs) have been deleted. After infection of HPRT-deficient rat cells by the vectors, transcriptional activity from the 5' LTR was undetectable and expression of the HPRT cDNA was dependent on an internal promoter. Removal of the LTR regulatory elements increased HPRT gene expression from an internal promoter, indicating interference between the two sets of transcriptional signals. Such disabled vectors may reduce the likelihood of undesirable genetic changes through insertional mutagenesis in cells infected with retroviral vectors.

Base Sequence↗
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

Carnitine reduces fasting ketogenesis in patients with disorders of propionate metabolism.

Patients with disorders of propionate metabolism have low plasma levels of free carnitine and excrete higher than normal quantities of esterified carnitine. The response to a 19 h fast was assessed as a physiological index of carnitine deficiency. In patients with propionic acidaemia and methylmalonic acidaemia a substantial ketogenesis developed in response to fasting. Supplementation with L-carnitine significantly reduced this ketogenic response.

Carnitine↗
PubMed1986

The effectiveness of benzoate in the management of seizures in nonketotic hyperglycinemia.

Patients with nonketotic hyperglycinemia generally have intractable seizures that are poorly responsive to anticonvulsant medication. No effective treatment has been consistently reported. In three patients with nonketotic hyperglycinemia, the oral administration of sodium benzoate in dosages designed to lower the cerebrospinal fluid concentration of glycine was followed by an abrupt change from frequent major seizures before treatment to no seizures, or only occasional minor ones, after treatment. This attenuation of seizures was associated with a decrease in the concentrations of glycine in both plasma and cerebrospinal fluid. There was no evident change in psychomotor development.

Amino Acid Metabolism, Inborn Errors↗
PubMed1985

Cloning of genes specifying carbohydrate catabolism in Pseudomonas aeruginosa and Pseudomonas putida.

A 6.0-kilobase EcoRI fragment of the Pseudomonas aeruginosa PAO chromosome containing a cluster of genes specifying carbohydrate catabolism was cloned into the multicopy plasmid pRO1769. The vector contains a unique EcoRI site for cloning within a streptomycin resistance determinant and a selectable gene encoding gentamicin resistance. Mutants of P. aeruginosa PAO transformed with the chimeric plasmid pRO1816 regained the ability to grow on glucose, and the following deficiencies in enzyme or transport activities corresponding to the specific mutations were complemented: glcT1, glucose transport and periplasmic glucose-binding protein; glcK1, glucokinase; and edd-1, 6-phosphogluconate dehydratase. Two other carbohydrate catabolic markers that are cotransducible with glcT1 and edd-1 were not complemented by plasmid pRO1816: zwf-1, glucose-6-phosphate dehydrogenase; and eda-9001, 2-keto-3-deoxy-6-phosphogluconate aldolase. However, all five of these normally inducible activities were expressed at markedly elevated basal levels when transformed cells of prototrophic strain PAO1 were grown without carbohydrate inducer. Vector plasmid pRO1769 had no effect on the expression of these activities in transformed mutant or wild-type cells. Thus, the chromosomal insert in pRO1816 contains the edd and glcK structural genes, at least one gene (glcT) that is essential for expression of the glucose active transport system, and other loci that regulate the expression of the five clustered carbohydrate catabolic genes. The insert in pRO1816 also complemented the edd-1 mutation in a glucose-negative Pseudomonas putida mutant but not the eda-1 defect in another mutant. Moreover, pRO1816 caused the expression of high specific activities of glucokinase, an enzyme that is naturally lacking in these strains of Pseudomonas putida.

Aldehyde-Lyases↗
PubMed1985

Proximal renal tubular acidosis in methylmalonic acidemia.

A patient with methylmalonic acidemia was found to have a persistent hyperchloremic acidosis. Investigation documented the presence of a proximal renal tubular acidosis. Between 14 and 18 months of age the urinary pH was as high as 8.0 when the serum bicarbonate was 17 mEq/liter and the threshold for bicarbonate was at 16-17 mEq/liter. When restudied at 33 months of age, the threshold had risen to 20 mEq/liter, but this was still abnormal and supplemental treatment was required to keep the serum concentration of bicarbonate above 20 mEq/liter. It is postulated that organic acid metabolites which accumulate in this and related disorders may interfere with renal tubular function as has been shown for maleic acid in experimental animals.

Acidosis, Renal Tubular↗
PubMed1985

Alanine decreases the protein requirements of infants with inborn errors of amino acid metabolism.

Supplementation with alanine was found to increase growth in weight and nitrogen balance in 5 infants with a variety of inborn errors of amino acid metabolism receiving diets restricted in protein. The addition of alanine to the regimen led to a mean increase in weight of 15 g/day. This and the increased nitrogen balance of 15 mg/kg/day were highly significant statistically. In addition a dose-response effect of alanine was observed. The effect of alanine was compared with that of a supplemental mixture of essential and non-essential amino acids, lacking only those considered to be toxic in these patients. Alanine at 0.05 g/kg was as effective in promoting growth in weight as 1.05 g/kg of the amino acid mixture, while 0.25 g/kg of alanine was more effective than 0.70 g/kg of the amino acid mixture. The protein sparing anabolic effect of alanine is thought to be a reflection of the alanine glucose cycle.

Alanine↗
PubMed1984

Plasma and red blood cell fatty acid composition in children with protein-calorie malnutrition.

Plasma and red cell fatty acids were measured in 44 children with third degree malnutrition: 22 children with marasmus, 11 children with kwashiorkor, and 11 with marasmic kwashiorkor (MK). The presence of edema, dermatosis, hair changes, and hypoalbuminemia were positively correlated with the red cell percentage linoleic acid and negatively correlated with red cell percentage arachidonic acid. Red cell percentage linoleic acid in kwashiorkor was decreased from the control value of 15.3% to 10.9%. In marasmus and MK, there were significantly greater decreases, to 7.7% and 8.0%, respectively. Red cell arachidonic acid in kwashiorkor was significantly (P less than 0.001) decreased to 9.8% (control value of 13.1%) whereas in marasmus there was no significant change. Only one sample, plasma from an infant with marasmus, had any detectable eicosatrienoic acid (20:3,omega 9). Similar changes in fatty acid composition have been reported in infants with acrodermatitis enteropathica, in an infant with biotin deficiency, and in biotin-deficient rats.

8,11,14-Eicosatrienoic Acid↗
PubMed1983

Adjuvant chemotherapy of malignant fibrous histiocytoma of bone.

Malignant fibrous histiocytoma (MFH) is a pleomorphic sarcoma that is uncommon in children. It most frequently arises from the soft tissues; however, it has been recently established that primary bone MFH also exists. Surgical resection or amputation is the cornerstone of treatment for MFH of bone. But, with this modality of therapy alone the majority of patients develop either distant metastases or local recurrence. This study reports on three adolescent girls with MFH of bone who were successfully treated with radical resection and 18 months of adjuvant chemotherapy with vincristine, high dose methotrexate, Citrovorum Factor rescue, and Adriamycin. All three patients remain disease-free for a follow-up period of 42-48 months. The current regimen was well tolerated. Morbidity was minimal, with no patient developing any significant drug-related complications. The adjuvant chemotherapy regimen described appears to be effective in prolonging survival in patients with MFH of bone and appears to warrant further study in additional patients.

Adolescent↗
PubMed1981

Epidural metastasis by Wilms' tumor.

Metastatic spread is common in Wilms' tumor, but spinal epidural involvement is rare. We studied two patients in whom spinal cord compression developed during treatment of Wilms' tumor. Both patients had back pain and new pulmonary metastases months after the primary diagnosis was established. One case had evidence of adjacent vertebral involvement, and successful therapy was begun while the patient had minimal neurological deficits. The second patient had back pain initially without neurological deficit or abnormality on plain spine films, followed in one month by a rapid neurological deterioration. Despite a slow and nearly complete recovery after treatment with laminectomy, radiotherapy, and chemotherapy, her condition relapsed one year later, with a compressive lesion at a higher level. Our experience stresses the importance of early recognition of treatment of this complication of Wilms' tumor.

Back Pain↗
PubMed1981

Diagnostic procedures for evaluation of sarcomas of soft tissue and bone in childhood.

A wide spectrum of procedures are available to physicians to assist in the establishment of the diagnosis and extent of disease in soft tissue and bone sarcomas in childhood. Some of these, including computerized tomography, require further evaluation for full assessment of their value for specific sites. A physician must keep in mind the possibility of hazards, such as radiation exposure or complications of invasive procedures, when selecting an approach to diagnosis. Proliferation of effective procedures requires the exercise of care and sound judgment to prevent unnecessary duplication, waste and, in some instances, increased morbidity.

Bone Neoplasms↗