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Biomedical subjects

O Heby

Publications and source records attributed to O Heby.

At least 91 records · Page 5Linked to original sources
PubMed1980

Essential role of the polyamines in early chick embryo development.

The polyamines putrescine, spermidine and spermine were analyzed in chick embryos during the first 2 days of development. A rapid increase in the activity of ornithine decarboxylase (ODC), the initial and rate-limiting enzyme in polyamine synthesis, was observed immediately after onset of incubation. Peak activities were found at 15 and 23 h of incubation. The first peak coincides with gastrulation and the second peak with early neurulation in the embryo. All three polyamines varied in a similar manner as did ODC, with putrescine and spermidine at about the same level and spermine at a lower level. The ODC activity was blocked by alpha-difluoromethylornithine, an enzyme-activated irreversible inhibitor. The inhibitor was administered to embryos in ovo at 5 h of incubation, i.e. prior to the first major increase in ODC activity. This block prevented the accumulation of the polyamines and inhibited development as gastrulation, suggesting a decisive role for polyamines in this developmental event.

Animals↗
PubMed1978

Possible involvement of putrescine in nucleolar formation in early embryos.

Continuous treatment of developing eggs of the polychete Ophryotrocha labronica with alpha-methylornithine, which inhibits synthesis of putrescine, led to arrest of development at gastrulation. The present ultrastructural analysis suggests that the arrest of development is due to failure to form nuclei, and thus reveals a possible role for putrescine in nucleolar formation. Further support for this contention was provided by means of electron-microscopical autoradiography. It was found that newly synthesized putrescine, derived from administered 3H-ornithine, labeled the nucleoli intensely at the time of their normal appearance during gastrulation, the time at which the rate of endogenous putrescine synthesis is maximal. These observations have led to the conclusion that putrescine synthesis may be directly involved in formation of nucleoli.

Animals↗
PubMed1978

Simplified micro-method for the quantitative analysis of putrescine, spermidine and spermine in urine.

A simplified micro-method for the quantitative analysis of urinary polyamines is described. After acid hydrolysis of urine, the polyamines are converted to fluorescent 1-dimethylaminonaphthalene-5-sulfonyl (Dns; dansyl) derivatives and separated by means of thin-layer chromatography. Dns-NH2, which has been reported to interfere with the determination of putrescine, is well separated from di-Dns-putrescine. Putrescine, spermidine and spermine are quantitated by in situ scanning of their fluorescent spots on the chromatogram. The present method is both sensitive and reproducible. It eliminates a number of time-consuming steps and thus reduces preparative losses. Yet an adequate chromatographic resolution is obtained. Representative polyamine analyses of urine from normal volunteers and from cancer patients are reported. Elevated levels occur in the urines of pregnant women and of patients with various types of cancer.

Chromatography, Thin Layer↗
PubMed1978

Inhibition of putrescine synthesis blocks development of the polychete Ophryotrocha labronica at gastrulation.

Development eggs of the polychete Ophryotrocha labronica were analyzed for polyamines during the first 6 days after fertilization. The spermine content dominated initially, but gradually decreased. It was surpassed by putrescine, which rapidly increased to a maximum on the 3rd day, i.e., at the inception of grastrulation. The spermidine content was low during the entire period. Treatment of eggs with the putrescine synthesis inhibitor alpha-methylornithine from the onset of development led to developmental arrest at gastrulation and to an abnormally low content of putrescine in the treated embryos. Methylglyoxal bis(guanylhydrazone), an inhibitor of spermine and spermidine synthesis, had no visible effect of development. Our observations strongly suggest that putrescine synthesis is indispensable in early embryonic development of Ophryotrocha.

Animals↗
PubMed1978

Tumour cell death: the probable cause of increased polyamine levels in physiological fluids.

The occurrence of extracellular polyamines in Ehrlich ascites tumour-bearing mice was studied in relation to tumour growth. The concentration of putrescine and spermidine in cell-free ascites fluid and serum was found to increase significantly with increasing tumour mass. Data is presented which suggest that the observed accumulation of extracellular polyamines is a result of a continuous release from dead or dying tumour cells. This observation is consistent with the notion that extracellular polyamines accumulate during tumour growth and following radio- and chemotherapy as a result of tumour cell death, and emphasizes the potential clinical usefulness of the polyamine analysis for evaluating tumor cell kill.

Animals↗
PubMed1978

Urinary polyamine excretion during the menstrual cycle.

Urinary polyamines were measured by a fluorometric thin-layer chromatographic technique in samples collected daily throughout a single menstrual cycle by each of 13 healthy women. Polyamine excretion fluctuated considerably, but excretion of putrescine, spermidine, and spermine combined was consistently greatest during menstruation, sometimes extending into the early follicular phase of the cycle. Enhanced excretion of polyamines was also noticed in many individuals at the approximate time of ovulation.

Adult↗
PubMed1977

Population kinetics of an Ehrlich ascites tumor following treatment with methylglyoxal-bis(guanylhydrazone), a polyamine synthesis inhibitor.

Population kinetics of Ehrlich ascites tumor cells grown in vivo were studied following treatment with methylglyoxal-bis(guanylhydrazone) (MeGAG; NSC-32946), a potent chemotherapeutic agent and a specific polyamine synthesis inhibitor. MeGAG-treatment resulted in a continuous accumulation of cells in the S and G2 phases of the cell cycle, and, as a consequence, the rate of cell proliferation decreased. This finding emphasizes the importance of the polyamines for progression through the cell cycle.

Adenosylmethionine Decarboxylase↗
PubMed1977

Kinetics of cell proliferation and polyamine synthesis during Ehrlich ascites tumor growth.

The kinetics of cell proliferation and polyamine synthesis during Ehrlich ascites tumor growth were studied. The steady deceleration of the specific growth rate with increasing tumor mass that was observed was attributable to a prolongation of the cell cycle, particularly of the S and G2 phases. The cell cycle time (Tc) was 43.3 hr (TG1 equals 10.8, TS equals 26.8, and TG2 equals 5.7 hr) on the seventh day of growth and 76.0 hr (TG1 equals 14.0, TS equals 52.0, and TG2 equals 10.0 hr) on the tenth day of growth. The growth fraction showed a decrease from 0.77 to 0.60 during the 7- to 10-day tumor growth interval. The cell death rate remained low and essentially unchanged during this period. A high correlation was found between polyamine synthesis (ornithine decarboxylase activity) and the specific growth rate; the correlation coefficient was 0.985. There was also a high positive correlation between the cellular polyamine (spermidine and spermine) and nucleic acid content (spermidine: DNA equals 0.916, spermine: DNA equals 0.947, spermidine:RNA equals 0.907, and spermine: RNA equals 0.881). These observations suggest that there may be a functional coupling between polyamines and nucleic acids, and they support the hypothesis that polyamines play an important role in DNA replication and cell division.

Animals↗
PubMed1976

Biphasic stimulation of polyamine biosynthesis in primary mouse kidney cells by infection with polyoma virus:uncoupling from DNA and rRNA synthesis.

Infection of primary cultures of mouse kidney cells with polyoma virus causes a biphasic increase in the activities of L-ornithine decarboxylase (ODC; L-ornithine carboxy-lyase; EC 4.1.1.17) and S-adenosyl-L-methionine decarboxylase (SAMD; S-adenoxyl-L-methionine carboxy-lyase; EC 4.1.50), as well as in the level of the polyamines putrescine, spermidine, and spermine. An early peak occurs during the period when early viral mRNA is synthesized and prior to the onset of virus-induced synthesis of host cell DNA. A late peak coincides in time with the maximum rate of virus-induced synthesis of cellular DNA. A similar biphasic stimulation of polyamine synthesis is induced even when DNA synthesis is prevented by 5-fluorodeoxyuridine. Actinomycin D (AMD) in a dose that inhibits rRNA synthesis causes no inhibition of ODC or SAMD. In a dose that inhibits mRNA synthesis as well, short-term AMD treatment causes "superinduction" of ODC but inhibition of SAMD. Prolonged treatment with the high dose of AMD inhibits ODC as well, indicating that late ODC activity may be dependent on mRNA synthesized during early infection. Cycloheximide effectively obliterates the ODC and SAMD activities during the entire infectious cycle. Uncoupling from DNA and rRNA synthesis suggests that polyamine synthesis is regulated independently of these events. The experiments with AMD and cycloheximide suggest that the formation of ODC is subject to post-transcriptional control, whereas that of SAMD is regulated primarily at the transcriptional level.

Adenosylmethionine Decarboxylase↗
PubMed1976

Increase in the amount of nuclear RNA in liver of ascites tumour-bearing mice.

The effect of tumour growth on the liver of the host was studied in the Ehrlich ascites tumour system. During the experimental period there was no infiltration of tumour cells in the liver, and the increase in the proliferation rate of Kupffer cells and parenchymal cells was only small. An increasing stability of the liver cell nuclei towards disruption during the isolation procedure was found to accompany the ascites tumour growth. In parallel, there was an increase in the amount of nuclear RNA and in the cellular speridine concentration. The major cause of these changes is probably an increasing demand on the liver by the growing tumour, illustrated by the fact that an amount of protein exceeding that of the whole liver accumulates in the ascites fluid during tumour growth. A hypothesis according to which the cellular accumulation of spermidine may be involved in the stabilization of cell nuclei and in the accumulation of nuclear RNA is advanced.

Animals↗
PubMed1976

The relationship of polyamines in cerebrospinal fluid to the presence of central nervous system tumors.

Cerebrospinal fluid (CSF) polyamine concentrations were assayed in patients with and without central nervous system tumors, using a high-pressure liquid chromatographic technique. Definite elevations were found in the CFS polyamine concentrations of patients with untreated malignant central nervous system tumors when compared with those concentrations observed in the CSF of patients without neoplasia. Patients undergoing successful tumor therapy for malignant central nervous system tumors showed CSF polyamine concentrations that closely approximated the concentrations found in the CSF of patients without tumor.

Adenoma↗