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Biomedical subjects

A Schaefer

Publications and source records attributed to A Schaefer.

At least 19 recordsLinked to original sources

The comparative concurrent validities of the Shipley Institute of Living Scale and the Henmon-Nelson Tests of Mental Ability.

This study compared the abilities of the Shipley Institute of Living Scale and the Henmon-Nelson Tests of Mental Ability to predict Wechsler Adult Intelligence Scale-Revised (WAIS-R) scores in psychiatric hospital patients. The Henmon-Nelson DIQs accounted for about 50% more WAIS-R Verbal and Full Scale IQ variance than did the Shipley IQs, apparently because of their higher correlations with the Information, Vocabulary, and, perhaps, Similarities subtests. Because Henmon-Nelson scores were more variable and generally higher than their WAIS-R counterparts, statistical adjustments were needed to optimize Wechsler IQ estimates. Therefore, regression formulae and a conversion table for the estimation of WAIS-R Full Scale IQs from Henmon-Nelson and Shipley intelligence scores also are presented.

Adult

Induction of differentiation in Friend-erythroleukemia cells by aclacinomycin A: early transient decrease in c-myc and c-myb mRNA levels.

Chemical inducers of the differentiation are known to cause an early transient decrease in c-myc and c-myb mRNA levels in Friend erythroleukemia cells preceding the down-regulation of c-myc and c-myb expression in the course of irreversible terminal differentiation. We therefore investigated the early effect of the potent differentiation-inducing anthracycline antitumor antibiotic, aclacinomycin A, on the c-myc and c-myb mRNA levels in the Friend cell line, F4-6, using Northern blot analysis. Aclacinomycin A induced a rapid decrease in the levels of c-myc and c-myb transcripts within 0.5-1 h and 2-3 h, respectively. The time course of decline in c-myc and c-myb expression was similar to that observed with dimethylsulfoxide or after transcription blockage brought about by a high concentration of actinomycin D. By 12 to 18 h after aclacinomycin A exposure, the c-myc and c-myb mRNA levels had returned to about pretreatment levels. When the cells were treated with adriamycin, an anthracycline that reduces cell proliferation in F4-6 cells without increasing differentiation, an early decrease in c-myc and c-myb expression was not observed. These results suggest that the transient decrease in c-myc and c-myb mRNA levels in F4-6 cells may be an early differentiation-related biochemical effect of aclacinomycin A.

Aclarubicin

The polymorphism of a cytosine anion studied by electron paramagnetic resonance spectroscopy.

Electron addition to the nucleic acid base cytosine and several derivatives was studied in frozen aqueous solution and in aqueous glasses containing 10 M glucose, 7 M BeF2, 10 M LiCl and 8 N NaOH. Electron paramagnetic resonance spectroscopy revealed that three major types of spectra are obtained which can be classified into a group D giving a doublet (ca. 1.6 mT) and a group of triplet patterns T and T1 (ca. 3.0 mT total spread) which differ slightly in coupling values but which are both distinct from D by showing the loss of one sizeable proton coupling (ca. 1.0 mT) in deuterated solvents. Varying the type of glasses and other parameters such as pH, together with modification of the cytosine exocyclic groups, indicated that the triplet patterns represent electron adducts protonated at the amino group, whereas the doublets D should probably involve N3-protonated species. The equilibrium between doublets and triplets was found to depend strongly on the presence of Li+ and Be2+ and less strongly on pH or the presence of Na+, the former group of ions inducing the triplets. It is suggested that the influence of the ions derives mostly from their strength in stabilizing the amino-protonated tautomer of the electron adducts.

Anions

Is fetal acidosis in the human fetus maternogenic during labor? A reanalysis.

The purpose of this study was to investigate whether maternogenic fetal acidosis can occur at the time of labor and delivery and to evaluate the extent of the possible maternal contribution to fetal acidosis. We have therefore determined fetal and maternal lactate concentrations and acid-base status under various conditions in 589 women at the end of gestation and during labor. The results show that metabolic acidosis develops in all fetuses because of increased production of lactic acidosis is primarily of fetal origin: 1) the umbilical arteriovenous lactate differences were positive and large in steady-state conditions as well as in depressed newborns; 2) the conditions that could produce a net transfer of lactate from the mother to the fetus, namely a positive maternofetal gradient of lactate and proton, were rarely observed; and 3) the correlation between fetal and maternal lactate levels was very weak, with regression coefficients decreasing from near steady-state conditions to acute stress conditions, indicating that the increase in lactate in the fetus and mother occurs independently. This correlation indicates also that increased maternal lactate production under conditions of labor and delivery can make a contribution by affecting the rate of net transfer from fetus to mother. This is possible in approximately 6% of the fetuses.

Acidosis

Structure-activity relationship between anthracycline-induced differentiation and inhibition of glycoprotein synthesis in Friend erythroleukemia cells.

The effect of adriamycin, daunomycin, N,N-dimethyladriamycin, N,N-dimethyldaunomycin, pyrromycin, marcellomycin, and aclacinomycin A on erythroid differentiation and glycoprotein synthesis in Friend erythroleukemia cells, clone F4-6 was investigated. Whereas N-dimethylated natural anthracyclines, pyrromycin, marcellomycin, and aclacinomycin A stimulated erythroid differentiation (induction of hemoglobin synthesis), this was not seen with adriamycin, daunomycin and their N-dimethylated derivatives. The incorporation of 3H-mannose in glycoprotein was inhibited by the N-alkylated natural anthracyclines at a concentration at which they induced erythroid differentiation. N,N-Dimethyladriamycin and N,N-dimethyldaunomycin only inhibited 3H-mannose incorporation into glycoprotein at cytotoxic concentrations. However, adriamycin and daunomycin did not inhibit glycoprotein synthesis, even at high cytotoxic concentrations. Aclacinomycin A decreased the incorporation of 3H-mannose into proteins earlier than the incorporation into dolichol-linked oligosaccharide intermediates. Tunicamycin, a specific inhibitor of glycoprotein synthesis, failed to stimulate differentiation in Friend erythroleukemia cells. These results indicate a structure-specific induction of the differentiation and inhibition of glycoprotein synthesis in Friend cells by N-alkylated anthracyclines. The inhibition of glycoprotein synthesis may be involved in the induction of differentiation by N-alkylated anthracyclines, but it cannot be the only target for the differentiation-inducing effect of these substances.

Aclarubicin

The effects of changes in plasma amino acid concentrations on erythrocyte amino acid content.

In order to determine the effects of large variations in plasma amino acid concentrations upon human erythrocyte amino acid content, the plasma concentration of blood samples was enhanced (x 3.8) by adding amino acids or decreased (x 0.49) by plasma dilution. Before and after incubation (30 s at 37 degrees C), the erythrocyte contents were calculated from whole blood and plasma amino acid concentrations. Large and rapid plasma concentration variations led to significant erythrocyte changes in 11 amino acids. THR, CIT, alpha AB, VAL, MET, ILE, LEU, TYR, PHE, TRP, and ARG. Relationships between erythrocyte and plasma concentrations were determined for these amino acids. These observations were examined in the light of the role played by erythrocytes in blood amino acid transport.

Amino Acids

Lactate movements in the term human placenta in situ.

Movements of lactate through the human placenta in situ were derived from maternal and fetal blood sampling performed under conditions that approximate as closely as possible the normal fetal metabolic state. It is reported that, at the end of pregnancy, the human fetus produces lactate which is transferred to the placenta. The actuality of this lactate transfer coupled with proton transfer is discussed taking into account the results of multiple linear regression analysis determined between the umbilical arterio-venous lactate differences and fetal and maternal lactate and proton concentrations. It is finally assumed that this lactate is partly metabolized in the placenta, the remaining part being transferred from the placenta to the mother.

Adult

[Morphometric studies of the postnatal development of the articular system of the bulbus oculi in rabbits].

The postnatal development of oculo-motor reactions is probably caused partly by changes of the passive mechanical properties of the bulb joint system. The YOUNG's elasticity modulus seems to be a suitable parameter to describe these changes. For its calculation, the length and the cross section area of the extraocular muscles as well as the dimensions of the ocular bulb are necessary. Moreover, the bulb mass is needed to analyse the inertia of the bulb during each movement. The postnatal growth of these parameters was investigated and, by means of the linear regression analysis, we looked for the best fitted mathematical expression. By this, there is the possibility to estimate the morphological data for detailed longitudinal analysis of changes of the oculo-motor function if the age and the body mass, are known.

Animals

Heavy-ion-induced free radical formation in solid DNA-constituents: quantitative and structural aspects.

Electron spin resonance (ESR) spectroscopy was used to study free radical formation in solid, polycrystalline pellets of DNA-constituents. Dose-yield curves were obtained at low (ca 90 K) and ambient temperatures, and were analyzed for initial G-values (radicals per 100 eV absorbed energy). At both temperatures, values of one or more orders of magnitude below the corresponding x-ray values were found. Combination of x-ray and heavy-ion irradiation indicated an enhanced radical destruction as probable cause of reduced G-values. Structural aspects as analyzed from the ESR-powder spectra revealed differences in initial, low-temperature radical population and in decay reactions upon annealing between heavy-ion bombardment and low-LET irradiation.

Adenosine

Are there two biological parts in the second stage of labor?

In 228 patients, fetal blood pH, pCO2 and lactic acid were measured in two distinguishable parts of the second stage of labor. The 'first' part begins at full cervical dilatation and ends when the mother starts her first voluntary bearing down efforts. In our study, the fetal acid-base status did not change in this part, regardless of a late developing hypoxia. In contrast, higher levels of lactic acid and pCO2 and lower pH values were observed in the 'final' part of the second stage, indicating increasing acidosis. In this 'final' part, the fetuses with clinical signs of distress, as defined by an ominous Apgar score at birth, showed quicker and larger acid-base shifts than did the normal fetuses. Thus the two parts of the second stage of labor actually differ in their potential to stimulate fetal acidosis. Since such fetal acidosis may develop especially during the 'final' part of labor, we have concluded that special particular attention should be devoted to this part.

Acid-Base Equilibrium

Does fetal acidosis develop with maternal glucose infusion during normal labor?

The actual effects of glucose infusion on fetal acid-base status were studied during 125 normal deliveries in which plasma glucose and acid-base parameters were determined after maternal infusion of either 10% glucose or Ringer's solution. After 80 minutes, mean (+/- SD) plasma glucose levels were significantly higher in the glucose group (N = 59) than in the Ringer's group (N = 66), both for the mother (183.6 +/- 46.8 versus 95.3 +/- 18.0 mg/dL) and the fetus (108.4 +/- 41.4 versus 64.8 +/- 16.2 mg/dL). Fetal plasma lactate concentrations did not differ between the glucose and the Ringer's groups, but were significantly lower in the fetuses delivered by elective cesarean section in both groups. With glucose administration, fetal pCO2 was higher and pH values were lower than in the Ringer's group. However, the magnitude of acid-base status changes, indicated by both pH and pCO2 shifts (ie, the difference between umbilical artery and scalp values), failed to differ between the two groups. In fetuses with progressing hypoxia, no differences in any of the acid-base parameters were observed between glucose and Ringer's administration. These data indicate that at a glucose infusion rate of 30 g/hour, fetal acidosis, when it occurs, results from hypoxia rather than from maternal glucose administration.

Acidosis

[Recurrent abscess in correlation with a dermoid cyst].

Following an empyema of the shoulder joint the patient had to undergo twelve operations in 14 months to treat vast subcutaneous abscesses. An epidermoid cyst was extirpated in the end, whatafter no more abscess occurred.

Abscess

Inhibition of amino acid uptake and incorporation into proteins in Friend erythroleukemia cells by the anthracycline antitumor antibiotic aclacinomycin A.

Treatment of Friend erythroleukemia cells with aclacinomycin A caused a concomitant inhibition of the uptake of 14C-alpha-aminoisobutyric acid (AIB) and of the incorporation of 3H-alanine into proteins. The decrease in amino acid uptake and incorporation into proteins was dose-dependent and reached a maximum of 60% within 3 hours at the concentration of aclacinomycin A, 200 ng/ml. A comparison of the effect on protein incorporation of 3H-alanine and cell proliferation by various anthracycline antitumor antibiotics in a concentration range of 50-200 ng/ml revealed that two other N-alkylated anthracyclines, pyrromycin and marcellomycin, are also potent inhibitors of the incorporation of amino acids into proteins. Inhibition of amino acid incorporation into proteins correlated well with the reduction of cell number at a later time. In contrast, adriamycin and daunomycin inhibited the incorporation of 3H-alanine into proteins only weakly, although these substances were highly active at inhibiting cell proliferation. Studies with an inhibitor of RNA synthesis, actinomycin D, suggest that the concomitant inhibition of amino acid uptake and incorporation into proteins observed with aclacinomycin A is not due to a reduced RNA synthesis. In addition, aclacinomycin A, up to a concentration of 10 micrograms/ml, did not inhibit protein synthesis in a cell-free translational system from rabbit reticulocytes. These results indicate that the reduction of amino acid incorporation into proteins after treatment of Friend erythroleukemia cells with aclacinomycin A may be due to a reduced uptake of amino acids. Inhibition of the transport of 14C-AIB may be indicative for an interaction of aclacinomycin A with the plasma membrane.

Aclarubicin

Eradication of mouse melanoma by combined treatment with recombinant human interleukin 2 and recombinant murine interferon-gamma.

Successful immunotherapy of early s.c. or i.p. (B16) melanoma in syngeneic C57BL/6 (B6) mice was achieved with s.c. peri-lesional injections (for s.c. tumors) or i.p. injections (for i.p. tumors) of recombinant human interleukin 2 (rIL-2) and recombinant murine interferon-gamma (rIFN-gamma). Over a 28-day period, rIL-2 and rIFN-gamma were injected 14 times. Results with this combination were additive with s.c. tumors and synergistic with i.p. tumors. Treatment with 6,250 U-25,000 U of rIL-2 and 2 micrograms of rIFN-gamma began 1-3 days after s.c. inoculation of melanoma. On day 50, 87% (72/83) of mice thus treated were completely free of tumor. None of the 78 control mice (tumor + buffer) survived. Of mice receiving either rIL-2 or rIFN-gamma alone, 59% (47/79) and 53% (44/83), respectively, were tumor-free. I.p. tumors were also eradicated by i.p. injections of rIL-2 (50,000 U) with rIFN-gamma (5, 10, and 15 micrograms) as judged by absence of tumor in 81% (21/26) of mice autopsied between days 45 and 65. No control mice survived, and only 17% (2/12) and 20% (6/30) given either rIL-2 or rIFN-gamma separately (i.p.) were tumor-free. Doses of rIFN-gamma from 1-4 micrograms were more beneficial in eliminating 1-day s.c. melanomas than were higher doses, and local s.c. treatment was far superior to distant or systemic treatment. Non-adherent peritoneal or splenic cells from mice bearing 6-day-old i.p. melanomas and treated with one or both lymphokines on days 3 and 4 were used in cytotoxicity assays in vitro. Significant cytotoxicity against cultured melanoma cells was displayed by cells harvested from lymphokine-treated mice, but there was no evidence of the synergism observed with combination treatment of i.p. tumors in vivo. rIFN-gamma inhibited proliferation of melanoma cells in vitro, whereas rIL-2 stimulated proliferation at 1,000 U/ml. Plating efficiency was increased by at least 30% by culture with 100 U or 1,000 U of rIL-2/ml and both concentrations neutralized the inhibitory effect of 0.05 ng/ml of IFN-gamma, but not of 0.5 or 5.0 ng/ml.

Animals

Induction of erythroid differentiation by the anthracycline antitumor antibiotic pyrromycin.

The oligosaccharide-anthracyclines, aclacinomycin A, marcellomycin and musettamycin, are potent inducers of erythroid differentiation in hemopoietic cells lines of rodent and human origin. The present studies revealed that pyrromycin, a closely related monosaccharide-anthracycline, induced erythroid differentiation in Friend leukemia cells and in the human leukemia cell line K 562. Pyrromycin, marcellomycin and musettamycin, which possess an identical aglycone structure containing a Cl-hydroxyl group, exhibited relatively low optimal inductive concentrations. In contrast, the optimal inductive concentration of aclacinomycin A, which lacks the Cl-hydroxyl group, was markedly higher, i.e., the differentiation inducing capacity was lower. It should be noted, however, that the yield of differentiated cells following treatment with the monosaccharide-anthracycline pyrromycin was distinctly lower than that after treatment with the oligo-saccharide-anthracyclines, aclacinomycin A, marcellomycin or musettamycin. Thus, our data indicate that the efficacy of anthracyclines to induce erythroid differentiation is related to a) the presence of a Cl-hydroxyl group in the aglycone and b) the presence of an oligosaccharide side chain.

Aclarubicin

Mutagenic and antimutagenic effects of 5-substituted 2'-deoxyuridines depending on the nature of the 5-substituent.

Various 5-substituted pyrimidine 2'-deoxyribosides with anti-herpes activity were investigated for their genotoxic activity. 5-Iodo-2'-deoxycytidine (IDC), 5-(2-chloroethyl)-2'-deoxycytidine (CEDC), 5-(3-chloropropyl)-2'-deoxyuridine (CPDU), (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU), 5-ethyl-2'-deoxyuridine (EDU), 2'-deoxyuridine (DU) and 2'-deoxythymidine (DT) were non-mutagenic in Salmonella typh. as well as in V79 Chinese hamster cells, 5-Iodo-2'-deoxyuridine (IDU) was moderately mutagenic and 5-(2-chloroethyl)-2'deoxyuridine (CEDU) was highly mutagenic in V79 cells; neither IDU nor CEDU were mutagenic in the bacterial assay. None of the compounds induced unscheduled DNA synthesis in primary rat hepatocytes. In addition, antimutagenic effects of 2'-deoxyuridines were discovered: in V79 cells, BVDU, EDU, DU and DT prevented the mutagenicity induced by CEDU; in these cells EDU also inhibited the mutagenicity induced by MNNG. In primary rat hepatocytes, IDU and EDU inhibited the induction of unscheduled DNA synthesis induced by MNNG, DMBA or UV-light. The compounds were inactive at inducing differentiation in hematopoietic cells. The significance of these data, particularly with regard to the use of 5-substituted 2'-deoxyuridines in anti-herpes therapy, is discussed.

Animals

The validity of fetal heart rate monitoring during the second stage of labor.

Fetal blood pH, pCO2, and lactic acid were measured before and after the final period of the second stage of labor in an attempt to better understand th validity fetal heart rate (FHR) monitoring at this time. Following a classification derived from Melchior, six FHR patterns were recognized: 0, 1, 2a, 2b, 3, and 4. In the second stage of labor, until bearing-down efforts began, the fetal acid-base status did not change regardless of the type of tracing. At the time of delivery, as compared with values measured before the beginning of the final stage, the highest shift of lactic acid, coupled with the lowest pH shift, was associated with the type 3 pattern. The most rapid increases of lactic acid and pCO2 and decreases in pH were associated with type 2b patterns. Both type 3 and 2b patterns were ominous, but low Apgar scores were more frequent in type 3 because the duration of the final stage of labor was longer. Working from the mean slopes of the shifts of biologic parameters as a function of time, theoretical limits were derived and discussed for safe duration of the final stage of labor.

Adult

Effects of medium amino acids on ouabain-sensitive 86Rb+ -uptake and membrane-potential dependent [3H]tetraphenylphosphonium accumulation in Friend erythroleukemia cells.

The effects of amino acids present in minimal essential medium were investigated on 86Rb+ -fluxes and on the membrane-potential dependent accumulation of the lipophilic cation [3H]tetraphenylphosphonium (TTP+) in logarithmically growing Friend erythroleukemia cells. The ouabain-sensitive 86Rb+ -uptake measured as well in complete growth medium as in Earle's balanced salt solution (EBSS) with amino acid composition present in growth medium, was 3 to 4-fold increased in comparison to the 86Rb+-uptake measured in pure EBSS only. The Na+,K+,2Cl- -cotransport measured as piretanide-sensitive 86Rb+-uptake was reduced in the presence of amino acids. Stimulation of the ouabain-sensitive 86Rb+ -uptake could be brought about by the addition of alanine alone or of the sodium ionophore monensin. In spite of the activation of the Na+,K+ -pump the membrane-potential dependent accumulation of [3H]TPP+ was about 40 per cent reduced in the presence of medium amino acids indicating a decreased membrane potential under these conditions. On the other hand, monensin which induces an electrically silent Na+ -influx via Na+/H+ -exchange was shown to hyperpolarize the membrane on the basis of [3H]TPP+-accumulation. These results suggest that the intensive uptake of neutral amino acids by Na+-cotransport in rapidly growing cells may be responsible for both stimulation of the Na+,K+ -pump and decrease in the transmembrane potential.

Amino Acids