Search PubMed⌕ Search

Biomedical subjects

G N Donnell

Publications and source records attributed to G N Donnell.

At least 37 records · Page 2Linked to original sources
PubMed1986

Pyruvate carboxylase defect: metabolic studies on cultured skin fibroblasts.

Oxidative studies using a number of radioactive carbon-labelled substrates on intact cultured skin fibroblasts from a patient with pyruvate carboxylase deficiency revealed dysfunction of the Krebs cycle. The suppression of CO2 production from aspartate but not glutamine strongly suggests that the defective function lies in the aspartate-malate shuttle. Furthermore, there is an unusual dependence on glutamine for the maintenance of growth of the patient's cells compared to normal cells. Glutamine could not be replaced by aspartate supplementation. A secondary defect resulting in accumulation of lipid material was also demonstrated in this study. It is speculated that the intracellular level of oxaloacetate may also be diminished in the patient's cells. Oxaloacetate is primarily generated by the carboxylation of pyruvate catalysed by pyruvate carboxylase.

Acetyl Coenzyme A↗
PubMed1986

Gonadal function in patients with galactosaemia.

Gonadal function was followed in 26 females and 12 males with galactosaemia due to deficiency of the enzyme galactose-1-phosphate (Gal-1-P) uridyl transferase over a 4 year period. Gonadal function was normal in males, but all females except two had evidence of acquired ovarian failure. Twelve females with ovarian failure documented at the beginning of this study continued to have either primary or secondary amenorrhoea on follow-up. Five of six patients, who previously had normal gonadal function developed either hypergonadotrophic hypogonadism or an abnormal response to gonadotrophin-releasing hormone (LRH) indicative of acquired ovarian damage. Seven of eight female patients, 1-12 years of age, who were evaluated for the first time had an exaggerated release of gonadotrophins during LRH stimulation tests diagnostic of gonadal insufficiency. The pathogenesis of ovarian failure remains unknown, but it appears likely that galactose or Gal-1-P is toxic to the ovary. The source of galactose metabolites, which may begin to accumulate prenatally and continue to damage the gonad in the postnatal period, is likely to be derived from the diet and from the endogenous synthesis of Gal-1-P from glucose via a variety of metabolic pathways. The testis appears to be relatively resistant to the effects of abnormal galactose metabolism.

Adolescent↗
PubMed1986

Methylmalonic and propionic acidemias: lipid profiles of normal and affected human skin fibroblasts incubated with [1-14C]propionate.

Normal human skin fibroblasts and those from methylmalonic acidemia and propionic acidemia patients were grown in culture. Following incubation with [1-14C]propionate, the major lipid classes in the cells were separated by thin layer chromatography and isolated fractions analyzed by radio gas chromatography for the presence of odd-numbered long-chain fatty acids; the pattern of even-numbered long-chain fatty acids was obtained also. Normal fibroblasts incorporated a small percentage of propionate into odd-numbered fatty acids which were present in all lipids studied. The abnormal cells incorporated a larger amount while maintaining the characteristic ratios of odd-numbered fatty acids found in the normal line. Most of the radioactivity was associated with phospholipids which are the predominant constituents of cell membranes. A characteristic C15/C17 ratio was found for different phospholipids and the triglyceride fraction; pentadecanoic acid was the principal odd-numbered fatty acid utilized in the assembly of complex lipids. Compared to even-numbered long-chain fatty acids the absolute amount of odd-numbered fatty acids was low (1-2%), even in affected cells. An unusual polar lipid fraction was isolated in the course of the study. In the normal cell it contained several unlabeled eicosanoids which were missing from the same fraction of both affected cell lines.

Amino Acid Metabolism, Inborn Errors↗
PubMed1985

Beta-glucuronidase deficiency. A heterogeneous mucopolysaccharidosis.

We studied two cases of beta-glucuronidase deficiency. One patient's disease was present at birth and the other patient's disease appeared in early childhood. The symptoms observed in both patients, although of differing severity, included peculiar facies, cloudy cornea, hepatosplenomegaly, hernia, kyphosis, recurrent infections, short stature, and developmental delay, as well as increased excretion of urinary chondroitin sulfate A/C and decreased levels of beta-glucuronidase activity. We reviewed all of the reported cases and examined the biochemical and clinical heterogeneity observed in this disorder.

Child↗
PubMed1985

Identification of a case of Y:18 translocation using a Y-specific repetitive DNA probe.

We have used a recombinant DNA clone derived from the Y-specific 3.4-kb repeats for in situ chromosome hybridization and Southern blotting analysis to identify a case of de novo Y;18 translocation. The proband has a chromosome complement of 46,XY and a variant chromosome 18 with a Q-bright and C-positive short arm. The father has a normal male karyotype of 46,XY. The mother has a female karyotype of 46,XX and an unusually large Q-bright satellite on one chromosome 22. In situ hybridization with the 3.4-kb probe to the metaphase preparations of family members indicated that the additional Q-bright material in the proband's variant chromosome 18 derived from the Y chromosome of his father, and not from the variant chromosome 22 of his mother. On Southern hybridization, the proband had approximately twice the amount of 3.4-kb repeats per cell as his father. These observations suggest a de novo genetic rearrangement in the proband which probably occurred during the father's spermatogenesis.

Child, Preschool↗
PubMed1984

Immune functions in methylmalonicaciduria.

A variety of phagocytic cell and lymphocyte assays were employed to evaluate the immune status of four patients with methylmalonicaciduria . One patient had a depressed absolute granulocyte count and two patients had depressed neutrophil and monocyte chemotactic responses. All subjects had normal neutrophil phagocytic and bactericidal activities. One patient had a decreased T-cell number; blastogenic responses to phytohaemagglutinin and pokeweed mitogen were normal in all subjects. B lymphocyte measurements were variably abnormal; two children had decreased B-cell numbers; two had marginally decreased IgG levels; a third had an undetectable rubella titre; and two had elevated serum IgE concentrations. In vitro exposure of normal cells to methylmalonic acid concentrations up to 50 mg/100 ml did not affect chemotactic or lymphoproliferative responses. In conclusion, although B-cell function may be affected, no consistent abnormality of lymphocyte or phagocytic cell functions could be attributed to the metabolic disorder.

Acidosis↗
PubMed1984

Partial ornithine transcarbamylase deficiency associated with recurrent hyperammonemia, lethargy and depressed sensorium.

A 6-year-old boy presented with recurrent coma associated with hyperammonemia and infection is reported. A liver biopsy revealed decreased ornithine transcarbamylase (OTC) activity (16% of normal). The enzymatic abnormality in the child is supported by the finding of elevated orotic acid excretion in his mother following a protein load, compatible with an X-linked pattern of inheritance. Since initiation of a dietary arginine supplement, the child has not had recurrent episodes of hyperammonemia.

Amino Acid Metabolism, Inborn Errors↗
PubMed1983

Neonatal pyruvate carboxylase deficiency with renal tubular acidosis and cystinuria.

This report concerns a patient with severe congenital lacticacidosis associated with proximal renal tubular acidosis and cystinuria. Enzyme studies with cultured skin fibroblasts obtained from the patient revealed zero pyruvate carboxylase activity, but propionyl-CoA carboxylase activity was normal. Administration of various vitamins in large amounts did not improve the clinical condition. In contrast, the patient began to thrive when her diet was supplemented with aspartic acid, asparagine, glutamic acid, and glutamine. The particular dietary treatment used and the biochemical findings merit consideration for management of future cases.

Acidosis↗
PubMed1981

Hypergonadotropic hypogonadism in female patients with galactosemia.

We evaluated gonadal function in 18 female and eight male patients with galactosemia due to transferase deficiency; it was normal in the males, but 12 females had signs of hypergonadotropic hypogonadism. All female patients had a 46,XX karyotype, normal levels of thyroid hormone and prolactin, and no anti-ovarian antibodies. The biologic activity of urinary gonadotropins was normal. Ultrasonography of the pelvis revealed that ovarian tissue was diminished or absent. Total estrogens increased in one of two patients after administration of human menopausal gonadotropin. The frequency of hypergonadotropic hypogonadism was higher in females in whom dietary treatment for galactosemia was delayed. Clinical course and mean erythrocyte galactose-1-phosphate and urinary galactitol levels did not correlate with ovarian function. We conclude that female patients with galactosemia have a high incidence of ovarian failure due to acquired ovarian atrophy. Galactose or its metabolites may be toxic to the ovarian parenchyma, particularly during the immediate neonatal period.

Adolescent↗
PubMed1980

Developmental aspects of galactosemia from infancy to childhood.

The developmental status of 60 galactosemic infants, their subsequent intellectual level, school status, visual-perceptual skills, and EEG results were analyzed. In addition, the intelligence of the parents and the unaffected siblings, as well as the educational and vocational status of the parents, were also investigated. The results reveal that the highest level of mental development was in the preschool age group. The lowest level, and still within normal limits, was in the school-age children. The overall findings are consistent with earlier observations that better progress is found in those individuals whose dietary control is instituted at the youngest age level.

Adolescent↗
PubMed1980

Medical genetics for the otorhinolaryngologist.

Genetic disorders involving the ear, nose and throat can be looked at in essentially the same way that one would view other genetic problems. It is important to differentiate genetic disorders from those due to environmental influences. This may be difficult on clinical grounds, since similar clinical features may be produced by different environmental factors or by different genes or groups of genes. When the cause of the disorder can be established, the risks involved in a family having further offspring usually can be determined reasonably readily. In the uncharacterized situations, empiric risk figures are employed. Abnormalities of genetic origin fall into one of three main groupings: chromosomal abnormalities, single gene mutations or polygenic inheritance. These situations are discussed and examples are given.

Chromosome Aberrations↗
PubMed1979

Ocular findings in cytogenetic syndromes.

Several cytogenetic syndromes are reviewed, and the salient ocular and facial abnormalities that might lead to a diagnosis are pointed out. Examples are given of mongoloid slant to the palpebral fissures, not only in Down's syndrome, but also in monosomy 9p, where, in addition, the triangular skull is almost diagnostic. Antimongoloid slant is found in trisomy 9p, where the eyes also have enophthalmos of monosomy 9p. Hypertelorism is another common finding in these syndromes; in monosomy 5p it is almost always present, although it occurs in other conditions as well, including trisomy 12p. The ring 22 syndrome has a distinguishing finding called "doe's eyes" because of the shape of the palpebral fissures. Trisomy 13 has numerous ocular findings as well as skull and facial involvements.

Child↗
PubMed1979

Regional mapping of the gene for human UDPGal 4-epimerase on chromosome 1 in mouse-human hybrids.

Somatic cell hybrids between mouse and human cells containing two different reciprocal translocations involving human chromosome 1, 46,X,t(1;X)(q12;q26) and 47,XX,+21,t(1;17)(p32;p13), were studied for the expression of human uridine diphosphate galactose 4-epimerase (UDPGal 4-epimerase, E.C. 5.1.3.2) by starch-gel electrophoresis. Analysis of the hybrid clones for the expression of the enzyme and the presence of the translocation chromosome 1 has permitted the assignment of the gene for human UDPGal 4-epimerase to the pter yields p32 region of chromosome 1.

Animals↗