A 31-year-old male is described who has macular cherry-red spots, increased deep tendon reflexes and and myoclonus without dementia. An older brother died at age 33 of a disease with similar symptomatology. Homogenates of cultured fibroblasts from the patient exhibited 2.6, 8.1 and 12.4% of normal mean sialidase (neuraminidase, N-acetyl-neuraminosyl glycohydrolase, EC 3.21.18) activity, respectively, against 2-(3'-methoxyphenyl)-N-acetyl-alpha-neuraminic acid, N-acetyl-neuramin-lactose and fetuin. Activities of 14 other lysosomal enzymes were within the range of normal control fibroblasts. The sialidase activities in fibroblasts from the patient's parents and children were 30 to 67% of normal. It is concluded that this is the first proven case of a new autosomal recessive disorder resulting in cherry-red spots, myoclonus and a sialidase deficiency.

Adult↗

PubMed1977

Ornithine decarboxylase activity during neonatal development of the rat ventral prostate.

The relationship between ornithine decarboxylase activity and growth has been examined in ventral prostates from rats aged 2--60 weeks. The incorporation of [125I]iododeoxyuridine in vitro was used to assess DNA-synthetic activity. During 2--7 weeks post-partum ornithine decarboxylase activity/prostrate and the protein content and wet weight increased exponentially. In contrast, the incorporation of [125I]iododeoxyuridine/prostate fell during the first 4 weeks. This decline was reversed at about the time when the systemic concentrations of gonadal androgens start to rise. After 10 weeks post-partum the incorporation of [1252]iododeoxyuridine/prostate and ornithine decarboxylase activity/prostate levelled off, whereas the DNA and protein content of the prostate continued to increase at a slow rate.

Aging↗

PubMed1977

Deoxyribonucleic acid and polyamine synthesis in rat ventral prostrate. Effects of age of the intact rat and androgen stimulation of the castrated rat with testosterone, 5 alpha-dihydrotestosterone and 5 alpha-androstane-3 beta, 17 beta-diol.

The relationship between polyamine synthesis, growth and secretion in vivo was examined in ventral prostates from: (a) intact rats aged 3-60 weeks; (b) animals castrated for 7 days before injection with 5 alpha-dihydrotestosterone (17 beta-hydroxy-5-alpha-androstan-3-one), testosterone and 5 alpha-androstane-3 beta, 17 beta-diol for up to 10 days; (c) rats injected with the 3 beta, 17 beta-diol immediately after castration. Ornithine decarboxylase activity and the concentrations of putrescine, spermidine and spermine were measured. DNA-synthetic activity was monitored by measuring [125I]iododoxyuridine incorporation. An enhanced spermidine/spermine molar ratio reflected increased activity of the prostate. The ratio was higher (greater than 2) in prostates from sexually immature animals, than in the intact adult (1.5), suggesting that the ratio was indicative of the proliferative activity of the tissue. However, in the androgen-stimulated castrated rat, enhanced spermidine/spermine ratios tended to correlate with hypertrophy and secretion. In both sets of experiments there was a linear relationship between protein and spermidine content. High spermidine/spermine molar ratios were the consequence of a relatively low rate of accumulation of spermine relative to spermidine and protein. The relationship between polyamine synthesis and DNA-synthetic activity was investigated in cultured prostate. A combination of insulin (3 mug/ml) and testosterone (0.1 muM caused a stimulatory response in the incorporation of [125I]iododeoxyuridine and in cell division, despite a depleted polyamine content and low ornithine decarboxylase activity in the cultured tissue.

Age Factors↗

PubMed1977

Photoreactivation of thymine dimers in UV-irradiated human cells: unique dependence on culture conditions.

UV-irradiated human fibroblasts in tissue culture were exposed to photoreactivating light in an attempt to demonstrate a light-dependent loss of thymine dimers from the acid-insoluble fraction of the DNA. The only experimental conditions in which this phenomenon was observed was if the cells were grown for at least 10 days in Dulbecco's modified Eagle's minimum essential medium. Such cells lost a maximum of between 10-30% of the thymine dimers from their DNA during illumination for 1 h. When cells were grown in a variety of other media the phenomenon was not observed. The present experiments do not discriminate between true enzymatic photoreactivation and a medium dependent photosensitization phenomenon that is not enzymatic in nature.

Animals↗

PubMed1976

Increased levels of sialic acid associated with a sialidase deficiency in I-cell disease (mucolipidosis II) fibroblasts.

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Cells, Cultured↗

PubMed1976

Hyperphenylalaninemia due to dihydropteridine reductase deficiency. Assay of the enzyme in fibroblasts from affected infants, heterozygotes, and in normal amniotic fluid cells.

Two infant siblings with modest elevations of serum phenylalanine concentrations had seizures and developmental regression: they died in their second year. Dihydropteridine reductase activity, which can be measured in normal cultured skin fibroblasts, was measured in the younger sibling and was absent. Parents of the two siblings and parents of a previously reported patient all showed 50% or less of the normal dihydropteridine reductase activity in their cultured fibroblasts. Dihydropteridine reductase activity is also present in normal cultured amniotic fluid cells, offering the possibility of prenatal diagnosis. Absence of dihydropteridine reductase results not only in a defect in the conversion of phenylalaning to tyrosine, but also in the biosynthesis of the neurotransmitters, dopamine, norephinephrine, and serotonin. Since deficiencies in these neurotransmitters would not be alleviated by a phenylalanine-restricted diet, it is important to establish the nature of the enzymatic defect in all suspected variants of phenylketonuria.

Adult↗

PubMed1976

Mannosidosis: phenotype of a severely affected child and characterization of alpha-mannosidase activity in cultured fibroblasts from the patient and his parents.

A three-year-old boy has coarse facial features, upper respiratory congestion, profound mental retardation, hepatosplenomegaly, increased height and head circumference, cataracts, a gibbus deformity, radiographic changes of dysostosis multiplex, and vacuolized peripheral lymphocytes. These findings are the most commonly reported clinical features in the previously described patients with mannosidosis. Our patient has a severe deficiency, and his parents have intermediate levels, of the acidic component of alpha-mannosidase in their cultured fibroblasts.

Cells, Cultured↗

PubMed1976

Uptake of (125I) iododeoxyuridine in cultured rat and human prostate: effects of insulin and testosterone.

DNA synthetic activity was monitored in rat and human prostate using [125I] iododeoxyuridine ([125I]UdR). Fresh prostate tissue from 6-week-old rats showed higher incorporation of [125I]UdR than that from 12- or 26-week-old rats. During culture for up to 6 days in the absence of hormones, the incorporation of [125I]UdR fell to a low level for all three age groups. Stimulatory effects were seen when rat prostates were cultured in the presence of insulin (3 mug/ml) and testosterone (10(-7) mol/l), the incorporation on day 4 of culture being commensurate with that of fresh prostrate of the corresponding age. Thus the magnitude of the response was higher for the 6-week-old prostate than that for the other two age groups. A similar age-related pattern of androgen stimulation was observed in experiments in which immature and adult castrated rats were injected daily with testosterone and the freshly removed prostates were incubated with [125I]UdR. Although insulin, by itself, had a stimulatory effect on [125I]UdR incorporation in cultured prostate, the magnitude of the response did not differ in the 6- and 26-week-old prostate tissue. Maximal stimulation was obtained using 25 mug insulin/ml. Tissue from a benigh prostatic hyperplasia was also responsive to insulin in culture but it differed from rat prostate in that increased proliferative activity occurred even in the absence of hormone stimulation. This spontaneous surge in activity during culture tended to mask the stimulatory effects of insulin and testosterone at concentrations of 3 mug/ml and 10(-7) mol/l respectively.

Age Factors↗

PubMed1976

Replication of type 2 herpes simplex virus in human endocervical tissue in organ culture.

The replication of type 2 herpes simplex virus in human endocervical tissue in organ culture was investigated. The temporal profile of virus replication was related to the initial virus inoculum; high input inocula induced a rapid increase in virus titre while lower multiplicities induced a more slow-rising increase in virus titre. Our evidence suggested that explants were capable of initiating and supporting virus replication for at least 2 weeks following establishment of the culture. Virus yields were optimal when explants were cultured at 37 degrees and in serum-supplemented medium. Explants also supported the replication of type 1 herpes simplex virus and a "non-human" herpes simplex virus (pseudo-rabies virus). The optimal conditions for replication of type 2 herpes simplex virus in human endocervical explants have been established and will provide a model permitting precise investigation of lytic or other virus-cervical cell interactions and their possible relationship to herpes virus-induced pre-invasive carcinoma of this organ.

Adult↗

PubMed1976

Proceedings: Polyamine synthesis in rat ventral prostate.

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Androgens↗

PubMed1975

Mannosidosis: deficiency of a specific alpha-mannosidase component in cultured fibroblasts.

Evidence is prisented which shows that the enzymatic defect in mannosidosis, the deficiency of alpha-mannosidase, is expressed in cultured skin fibroblasts from patients with mannosidosis. Additionally, by Cellogel electrophoresis, the enzyme can be separated into two major components (a heat stable component missing in mannosidosis fibroblasts with a pH optimum of 3.6-4.0 and a heat labile component present in mannosidosis fibroblasts with a pH optimum of 5.6-6.0). The specific activity and electrophoresis of alpha-mannosidase from cultured amniotic fluid cells are also shown to be similar to cultured skin fibroblasts.

Amniotic Fluid↗

PubMed1975

Differences in proliferative activity of rat and human prostate in culture.

The properties of human benign prostatic hyperplasia (BPH) and rat prostate were compared after culture in the absence of insulin and testosterone. Quantitative methods were used to assess changes in tissue composition and the height of the epithelial cells. BPH appeared less sensitive than rat prostate to withdrawal of hormone support, and the changes which occurred during culture of BPH were more typical of a repair mechanism to injury than of a castration effect. Cell kinetics was investigated using [125I] iododeoxyuridine and vincristine. Both approaches demonstrated a spontaneous surge in proliferative activity of BPH reaching a peak at about Day 4. In contrast, proliferative activity in rat prostate tended to fall over the period of 2-8 days of culture. The significance of these findings in terms of age linked effects is discussed.

Age Factors↗

PubMed1975

Ornithine decarboxylase activity and: [125I]iododeoxyuridine incorporation in rat prostate.

The relationship between ornithine decarboxylase activity and [125I]iododexyuridine incorporation was studied in prostates from castrated rats (aged 5, 26 and 80 weeks) injected daily with testosterone for up to 10 days. The results suggest that ornithine decarboxylase activity is a parameter of secretory activity, rather than growth, in the ventral prostate. In the dorsolateral prostate, ornithine decarboxylase activity tends to parallel [125I]iododeoxyuridine incorporation.

Animals↗

PubMed1975

Sister chromatid exchange in xeroderma pigmentosum cells that are defective in DNA excision repair or post-replication repair.

The formation of sister chromatid exchanges has been postulated to depend upon the action of DNA repair enzymes. Our experiments with various human cell lines show that the yield of sister chromatid exchanges is within normal limits in both excision-repair-defective and post-replication-repair-defective cells from the autosomal recessive disease, xeroderma pigmentosum. These results indicate that hypotheses invoking known DNA repair processes to acconnt for the recombination of sister chromatids are inadequate and that the exact enzymatic processes are as yet unknown.

Cell Line↗