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Biomedical subjects

A Schaefer

Publications and source records attributed to A Schaefer.

At least 55 records · Page 3Linked to original sources
PubMed1998

Intermediate and long-term side effects of high-dose radioiodine therapy for thyroid carcinoma.

UNLABELLED: The present investigation is an evaluation of intermediate and long-term side effects in patients after high-dose radioiodine treatment due to differentiated thyroid carcinoma. METHODS: A total of 203 patients were interviewed using a standardized questionnaire. RESULTS: After radioiodine treatment, 76.8% of the patients reported intermediate (from discharge up to 3 mo) or long-term (more than 3 mo after treatment) complaints, and 61.1% reported long-term side effects. Nonstochastic side effects included sialoadenitis, which occurred in 33.0% of cases, and 27.1% of patients suffered from a transient loss of taste or smell. More than 1 yr after the last radioiodine application, 42.9% of patients suffered from reduced salivary gland function. Complete xerostomia occurred in 4.4% of patients. Hematological abnormalities were found in 9 patients. In 28.1% of patients a transient episode of alopecia was reported. In 22.7% of patients chronic or recurrent conjunctivitis was reported, and 4 patients underwent dacryocystorhinostomy; 13.8% of patients suffered from an increased frequency of influenza, but 3.4% reported a reduced occurrence of such infections. For sialoadenitis, the loss of taste/smell and dry mouth, the dependence on accumulated activity was significant. CONCLUSION: Severe long-term side effects are rare after high-dose radioiodine treatment. Moderate side effects are common. The side effects are commonly the result of radiation damage to the salivary glands. The frequency of such complaints advocates regular protection of the salivary glands.

Alopecia↗
PubMed1998

Normal short-term renal response to acute volume expansion in heart transplant recipients: a role for atrial natriuretic peptide?

BACKGROUND: The breakdown of blood pressure and body fluid homeostasis observed in heart transplant (Htx) recipients may partly be due, as in heart failure, to a blunted renal response to elevated atrial natriuretic peptide (ANP). METHOD: This possibility was addressed through determination of the relationship between ANP, the urinary cyclic guanosine monophosphate (cGMP), a biologic marker of ANP renal activity, and the early renal responses to 10 mL/kg isotonic saline infusion over 30 minutes in 8 control subjects and 8 matched Htx recipients. RESULTS: Urine flow, natriuresis, and urinary cGMP excretion increased similarly in both groups, resulting in elimination of, respectively, 1/2 and 2/3 of the sodium and the water load during the experiment that lasted 4 hours and 30 minutes. Plasma renin and aldosterone decreases were similar in both groups. Elevated ANP further increased in Htx after saline infusion (from 19.5 +/- 3.7 to 33.8 +/- 5.6 pmol/L, P < .001). Plasma cGMP paralleled ANP in both groups (r = 0.81; P < .001). Significant correlations were observed between plasma ANP and urinary cGMP excretion (r = 0.48, P < .025 and r = 0.43, P < .05 in Htx recipients and control subjects) and between plasma ANP and urinary sodium excretion (r = 0.64, P < .001 in Htx recipients). CONCLUSION: In spite of a relative renal hyporesponsiveness to the cardiac hormone, with higher plasma ANP being not associated with increased renal excretions in Htx recipients, ANP is likely to participate in the appropriate short-term renal response to acute volume expansion in Htx recipients.

Aldosterone↗
PubMed1997

Signalling mechanisms in erythropoiesis: the enigmatic role of calcium.

The glycoprotein hormone, erythropoietin is the principal regulator of the production of circulating erythrocytes by controlling proliferation, differentiation and survival of its target erythroid progenitor cells. The receptor for erythropoietin is a type I cytokine receptor lacking intrinsic tyrosine kinase activity. It mediates tyrosine phosphorylation through its association with nonreceptor tyrosine kinases such as JAK2 and initiates a cascade of signalling events in response to erythropoietin. Significant progress has been made in identifying signalling pathways triggered by erythropoietin. However, the exact signalling mechanisms mediating the known physiological effects of erythropoietin in erythroid progenitor cells are poorly understood. There are many open questions including the role of Ca2+ in erythropoietin induced signal transduction. Although the results concerning the effect of erythropoietin on [Ca2+]i in various erythroid cells are conflicting, [Ca2+]i-increasing agents mimic the effect of erythropoietin on c-myb expression and activate the program of haemoglobin synthesis in murine erythroleukemia cells. An attempt is made in this review to survey recent data on the erythropoietin-induced signal transduction with respect to the different physiological effects of this hormone.

Animals↗
PubMed1997

[18Fluoro-FDG SPECT for the demonstration of hibernating myocardium: an interim account].

AIM: The present investigation demonstrates an intraindividual comparison of FDG-PET and FDG-SPECT. MATERIAL AND METHODS: Thirty patients with CHD and planed revascularisation underwent both modalities. Myocardial perfusion was evaluated by 99mTc-MIBI SPECT. The myocardium was divided into 25 segments and the results were compared by two experienced observers. RESULTS: Segmental concordance of FDG-PET and -SPECT was 94.1%. PET indicated a higher percentage of hibernating myocardium (8.9% vs. 5.7%) and a lower rate of matched defects (11.5% vs. 16.0%). In 22 cases the need for revascularisation was assessed identically. In the remaining 8 patients FDG-PET and FDG-SPECT required an intervention in 6 and 2 cases, respectively. CONCLUSION: The results of FDG-PET and FDG-SPECT showed a high segmental concordance, but the individual assessment of hibernation worthwhile for revascularisation demonstrated important differences in patient management.

Aged↗
PubMed1996

Ca2+/calmodulin-dependent and -independent down-regulation of c-myb mRNA levels in erythropoietin-responsive murine erythroleukemia cells. The role of calcineurin.

Down-regulation of c-myb mRNA levels by [Ca2+]i-increasing agents (A23187, thapsigargin, cyclopiazonic acid) and erythropoietin was comparatively studied in the erythropoietin-responsive murine erythroleukemia cell line, ELM-I-1. The Ca2+-induced suppression of c-myb mRNA could be inhibited by the calmodulin antagonists trifluoperazine and calmidazolium, as well as by cyclosporin A, an inhibitor of the Ca2+/calmodulin-dependent protein phosphatase 2B (calcineurin). KN-62, an inhibitor of Ca2+/calmodulin-dependent protein kinases, did not antagonize the Ca2+-mediated decrease in c-myb mRNA. In cyclosporin A-treated ELM-I-1 cells, a close correlation could be demonstrated between the antagonization of the Ca2+ effect on c-myb mRNA levels and inhibition of the calcineurin phophatase activity. On the other hand, FK506, which did not inhibit calcineurin activity in ELM-I-1 cells, failed to prevent the Ca2+-mediated decrease in c-myb mRNA. The erythropoietin-induced down-regulation of c-myb mRNA levels could be demonstrated also in the presence of EGTA and was resistant to calmodulin antagonists and cyclosporin A. In addition, no increase in [Ca2+]i was observed in ELM-I-1 cells in response to erythropoietin. Cyclosporin A inhibited the Ca2+-induced hemoglobin production, while the erythropoietin-mediated increase in hemoglobin synthesis was not affected. The results indicate that the Ca2+-induced decrease in c-myb mRNA and increase in hemoglobin synthesis is mediated by calcineurin, while these effects of erythropoietin occur independently of Ca2+ in ELM-I-1 cells. Calcineurin may be involved in the regulation of c-myb expression in erythroid precursor cells and Ca2+ signals via calcineurin may positively modulate the differentiation inducing action of erythropoietin.

Animals↗
PubMed1995

[Performance of a multispect 2 gamma camera for imaging 511-keV gamma rays].

The performance of a modified Multispect 2 gamma camera, which was supplied with two pairs of collimators constructed for imaging positron emitters was tested. The measurements involved the determination of sensitivity and of spatial resolution. The septal penetration was calculated approximately using two different methods. The spatial resolution determined by FWHM as measured by planar imaging in water at 10 cm distance from the collimator was evaluated as 14.0 mm with collimator 511-A and 12.5 mm with collimator 511-B. Using a Gaussian fit of the line-spread function septal penetrations of 12% with collimator 511-A and of 36% with collimator 511-B were calculated. The absolute system sensitivity measured with 18F was 66 cpm with collimator 511-A and 98.7 cpm/37 kBq with collimator 511-B. The high sensitivity with collimator 511-B may be explained, at least partially, by the high septal penetration.

Deoxyglucose↗
PubMed1995

DMSO-like rapid decrease in c-myc and c-myb mRNA levels and induction of differentiation in HL-60 cells by the anthracycline antitumor antibiotic aclarubicin.

The anthracycline antitumor antibiotic aclarubicin is known to induce granulocytic differentiation in the human myeloid leukemia cell line HL-60. We investigated whether this effect is accompanied by changes in the expression of the protooncogenes c-myc and c-myb. Treatment of HL-60 cells with aclarubicin, 50 nM, caused a rapid decrease in c-myc and c-myb mRNA levels within 1 h and 2 h, respectively. In parallel, we demonstrated a strong induction of superoxide-anion production on day 8 of treatment. The kinetics of the effect of aclarubicin on c-myc and c-myb expression were comparable to those associated with the dimethylsulfoxide-induced granulocytic differentiation in this cell line, or to those observed following a chase with actinomycin D, 4 microM. Since aclarubicin partially inhibited total- and poly(A)(+)-RNA synthesis, this macromolecular synthesis inhibition may be causally related to the decrease in c-myc and c-myb mRNA levels. In contrast, the conventional anthracycline doxorubicin, which did not initiate differentiation, failed to affect c-myc or c-myb mRNA levels even in high cytotoxic concentrations, indicating that the suppression of c-myc and c-myb mRNA levels may be an early differentiation-related effect of aclarubicin. On the other hand, actinomycin D, 12.5 nM, and novobiocin, 300 microM, two other known inducers of granulocytic differentiation in HL-60 cells, did not induce an early decrease in c-myb or c-myc expression. Therefore, the immediate suppression of c-myc and c-myb mRNA levels, apparently, is not an obligatory step in chemically induced myeloid differentiation in HL-60 cells, but the common phenomenon in DMSO- and aclarubicin-induced differentiation.

Aclarubicin↗
PubMed1994

Early transient suppression of c-myb mRNA levels and induction of differentiation in Friend erythroleukemia cells by the [Ca2+]i-increasing agents cyclopiazonic acid and thapsigargin.

Cyclopiazonic acid and thapsigargin, inhibitors of the endoplasmic reticulum Ca2+ pump were shown to elevate [Ca2+]i in Friend erythroleukemia cells, line F4-6, at concentrations of 1-5 microM and 0.5-2 nM, respectively. At the same concentrations, these agents induced a strong suppression of c-myb mRNA levels within 3 h, whereas c-myc expression remained unaffected. The c-myb expression recovered and approached pretreatment levels at 9-12 h of incubation. The decrease in c-myb mRNA was prevented in Ca(2+)-free medium. Treatment of F4-6 cells with EGTA led to a transient increase in c-myb mRNA with the same kinetics as the Ca2+ pump inhibitor-induced suppression, indicating that c-myb expression is bidirectionally regulated by changes in [Ca2+]i. Studies on the differentiation status of F4-6 cells following cyclopiazonic acid or thapsigargin exposure demonstrated a marked increase in beta-globin mRNA synthesis at 60h and in hemoglobin production at 96 h. These results provide further evidence that a rise in the cytosolic Ca2+ concentration is capable, in Friend erythroleukemia cells, of inducing an early transient suppression of c-myb mRNA levels, which is followed by terminal erythroid differentiation.

Animals↗
PubMed1994

[Instruments for measuring the quality of life of severely injured patients].

Trauma can be defined as either a somatic injury or a psychological reaction in the person affected. The emotional disturbances and psychosocial problems of trauma patients in particular, though still measurable a year or even longer after the event, have rarely been taken into account in surgical studies. Quality of life is a relevant endpoint in multiple trauma patients, insofar as rehabilitation seems to be complicated by non-efficient psychological coping. With reference to the prerequisites for a scientifically sound measuring method four instruments are described that seem to be suitable for measuring quality of life in multiple trauma patients. In addition, practical advice is given for the design of longitudinal studies focused on quality of life in trauma patients.

Activities of Daily Living↗
PubMed1993

Calcium ionophore-induced transient down-regulation of c-myb mRNA levels in Friend erythroleukemia cells.

The effects of calcium ionophores A23187 and ionomycin on the c-myb and c-myc mRNA levels have been investigated in the Friend erythroleukemia cell line F4-6 using Northern blot analysis. Treatment of the cells with 0.5-4 microM A23187 or 1-4 microM ionomycin induced a concentration-dependent decrease in c-myb mRNA; this decrease was abolished by EGTA. c-myc mRNA levels were only moderately affected. After 12-24 h of calcium ionophore exposure, c-myb mRNA returned to pretreatment levels. No similar decrease in c-myb mRNA was seen with the sodium ionophore monensin (up to 16 microM). The dimethyl sulfoxide-induced suppression of c-myb and also of c-myc mRNA levels was not prevented in Ca(2+)-free medium and thus appeared Ca(2+)-independent. A23187 and ionomycin were capable of inducing beta-globin mRNA synthesis in F4-6 cells. Prolonged calcium ionophore exposure, however, strongly reduced cell viability and resulted only in a slight hemoglobin increase at lower concentrations. These results suggest that a rise in [Ca2+]i may be a signal leading to a transient decrease in c-myb mRNA and the initiation of erythroid differentiation in Friend cells. The transient suppression of c-myb mRNA levels represents a common feature of the action of dimethyl sulfoxide and calcium ionophores.

Actins↗
PubMed1993

Decreased resistance to N,N-dimethylated anthracyclines in multidrug-resistant Friend erythroleukemia cells.

Doxorubicin-resistant Friend erythroleukemia cells, line F4-6 ADM2R, were selected by exposure of wild-type F4-6 cells to doxorubicin concentrations of up to 1 microgram/ml. In these cells, increased expression of multidrug resistance (MDR) genes was demonstrated by Northern blot analysis. The growth-inhibitory effect of doxorubicin, daunorubicin, N,N-dimethyldoxorubicin, N,N-dimethyldaunorubicin, morpholinodoxorubicin, and pyrromycin was comparatively investigated in resistant and wild-type cells. The doxorubicin-resistant F4-6 cells showed approx. 200-fold resistance to doxorubicin and about 100-fold resistance to daunorubicin with respect to the drug-sensitive counterpart. A dramatic decrease in resistance was observed for the N,N-dimethylated derivatives of doxorubicin and daunorubicin as well as for the N,N-dimethylated natural anthracycline pyrromycin and for morpholinodoxorubicin. Uptake studies using [14C]-daunorubicin and [14C]-N,N-dimethyldaunorubicin in resistant F4-6 cells showed a decreased accumulation of daunorubicin but no significant reduction in N,N-dimethyldaunorubicin accumulation as compared with the wild-type cells. Treatment with verapamil led to increased intracellular levels of daunorubicin in resistant cells, whereas an excess of N,N-dimethyldaunorubicin did not have this effect. Thus, the decreased resistance of the doxorubicin-resistant F4-6 cells to the N-alkylated anthracyclines may at least in part be due to a reduced affinity of these compounds for the efflux pump. The results indicate that the dimethylation of the amino group of the anthracycline sugar moiety and its incorporation within a morpholinyl ring may overcome MDR by similar mechanisms.

Antibiotics, Antineoplastic↗
PubMed1993

Free radicals from polycrystalline pyrimidines and purines upon heavy ion bombardment at low temperatures: an electron spin resonance study.

The formation of free radicals in polycrystalline samples of the DNA constituents thymine, cytosine, and adenosine after bombardment with heavy ions at about 100 K was investigated by electron spin resonance (ESR) spectroscopy. Spectra were observed at 77 K after irradiation at 100 K, upon annealing to 300 K and after storage at 300 K. Individual radical patterns were isolated from the spectra by computer manipulation and assigned to structures by powder-simulations based on literature data. The spectra of thymine contain an allyl radical, the octet pattern of the 5-thymyl radical and contributions of the 6-yl radical formed by net hydrogen gain at carbon C5. The latter species is also present in cytosine which in addition displays the pattern due to H-addition at the carboxyl oxygen C2. Adenosine exhibits two H-addition radicals, one at C2, the other at C8. Additionally, the spectra of all DNA subunits studied contain as a radical component a Gaussian singlet of about 0.9 mT line width. The spectra obtained at low temperature already contain the secondary radicals but exhibit a large linewidth. This feature is attributed to dipolar coupling caused by radicals in close proximity.

Adenosine↗
PubMed1993

Role of cardiac innervation in atrial natriuretic peptide secretion in transplanted heart recipients.

To investigate whether cardiac innervation modulates atrial natriuretic peptide (ANP) secretion, we performed acute volume expansion on eight normal and eight matched (age, weight, and total blood volume) transplanted denervated heart patients (Htx), while monitoring fluid-regulating hormone, systemic blood pressure, and echocardiographic atrial area changes. At rest, plasma ANP and guanosine 3',5'-cyclic monophosphate (cGMP) were lower in control subjects than in Htx (45 +/- 16 vs. 103 +/- 35 pg/l and 0.9 +/- 0.3 vs. 3.5 +/- 1.4 pM, respectively; P < 0.001). Plasma active renin, aldosterone, and catecholamines did not differ significantly in the two populations, whereas arginine vasopressin and cortisol were higher in controls (P < 0.01 and P < 0.005). Although volume expansion (+15%) and atrial stretch were similar in the two groups, plasma ANP and cGMP increased significantly only in the Htx group (103 +/- 35 to 189 +/- 69 pg/l and 3.5 +/- 1.4 to 5.8 +/- 1.4 pM, respectively; P < 0.001). The decrease observed for the other hormones was not significant except for arginine vasopressin and cortisol (P < 0.05 and P < 0.001) in the control group. These results support the hypothesis of an inhibitory role of cardiac innervation in biologically active ANP secretion in humans, at rest and after acute volume expansion.

Adult↗
PubMed1993

Performance of young pigs: relationships with periparturient progesterone, prolactin, and insulin of sows.

Blood collected from 54 sows over 2 to 8 d of the periparturient period was assayed for progesterone, insulin, and prolactin to determine whether the sows' hormonal state was correlated with perinatal pig mortality and weight gain. Sows with larger litters had higher concentrations of progesterone and prolactin and a lower concentration of preprandial insulin during the 48 h preceding parturition. Pig mortality was higher in larger litters and involved pigs of lower birth weight. Most pigs that died lost weight during the 24 to 48 h that preceded their deaths. Litters with lower weight gain during the first 24 h postpartum tended to have higher mortality during the next 48 h. For some sows, progesterone remained elevated during the 48 h postpartum and litters of these sows had lower than average 3-d weight gains. Low milk intake by pigs is a major cause of death and poor growth, and we suggest that poor milk production by the sow is one contributing factor. Elevated postpartum progesterone may inhibit lactogenesis and contribute to poor pig performance.

Animals↗
PubMed1992

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↗
PubMed1992

Direct radiation action of heavy ions on DNA as studied by ESR-spectroscopy.

The effects of heavy ions on the mechanisms of free radical formation in DNA-constituents as compared to low-LET irradiation are investigated by means of Electron Spin Resonance (ESR) spectroscopy. Dose-yield curves were measured at low (T < 100 K) and ambient temperatures in order to obtain the G-value, that is number of radicals formed per 100 eV absorbed energy. These G-values show a characteristic LET-dependence and are one to two orders of magnitude lower than for low-LET irradiation. Measurements on 2'Deoxycytidine at 300 K using combined heavy ion and X-ray irradiation methods suggested that this effect can be partially explained by a destruction of radicals during the irradiation.

Adenosine↗
PubMed1992

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↗