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At least 1,153 records · Page 64Linked to original sources
PubMed2005

Cerebrovascular characterization of clazosentan, the first nonpeptide endothelin receptor antagonist shown to be clinically effective for the treatment of cerebral vasospasm. Part II: effect on endothelin(B) receptor-mediated relaxation.

OBJECT: The disturbed balance between nitric oxide and endothelin (ET)-1 in the cerebrovasculature seems to play a major role in the development of cerebral vasospasm after subarachnoid hemorrhage. Endothelin-1 represents the contractile part in this balance. In addition to the prevailing ET(A) receptor-dependent contractile effect, ET-1 also has ET(B) receptor-mediated vasodilatory attributes. The aim of the present study was to define the actual selectivity of clazosentan, the first putative highly ET(A) receptor-selective antagonist clinically proven to be effective in the treatment of vasospasm in the cerebrovasculature. METHODS: Rat basilar artery ring segments with endothelial function were used for the measurement of isometric force. Concentration effect curves were constructed by cumulative application of sarafotoxin S6c, ET-1, or big ET-1 in the presence or absence of clazosentan (10(-9) to 10(-6) M) after a precontraction was induced by prostaglandin F2alpha. The inhibition by clazosentan was estimated by the value of the affinity constant (pA2). The relaxation induced by sarafotoxin S6c, ET-1, and big ET-1 was inhibited in a competitive manner by clazosentan, yielding pA2 values of 7.1, 6.7, and 6.5, respectively. The selectivity to the ET(A) receptor in the cerebrovascular system was approximately two logarithmic units. CONCLUSIONS: The present investigation shows a competitive inhibition of ET(B) receptor-mediated relaxation in cerebral vessels by clazosentan in therapeutically relevant concentrations. Thus, additional clinical trials should be undertaken to evaluate clazosentan concentrations in cerebrospinal fluid. Furthermore, the present data may be taken to describe the pharmacological properties for an ET receptor antagonist specifically tailored for the treatment of pathological conditions of impaired cerebral blood flow.

Animals↗
PubMed2004

Isolation and characterization of the 5'-flanking region of the growth hormone secretagogue receptor gene from black seabream Acanthopagrus schlegeli.

Ghrelin, the recently discovered endogenous ligand for growth hormone secretagogue receptor (GHSR), is widely expressed and involved in regulating diverse physiological functions in addition to stimulation of growth hormone (GH) secretion. Previous studies have demonstrated the functional significance of the ghrelin/GHSR system, yet the transcriptional regulation of the ghrelin and GHSR genes are poorly understood. We have recently cloned the GHSR cDNA from the pituitary of black seabream Acanthopagrus schlegeli. In the present study, we have isolated a 2.1 kb 5'-flanking region of the GHSR gene from the same species and have investigated, for the first time, the transcriptional regulation of GHSR from a non-human species. The 5'-flanking region of the seabream GHSR gene was found to contain a number of unique putative transcription factor-binding sites different from the human counterpart. Functional characterization of the 5'-flanking region in several cell lines indicates that the region between -1423 and +19 contains sufficient elements for promoter function. Moreover, progressive 3'-deletion analysis suggests the presence of negative regulatory element(s) and essential cis-acting element(s) at -514/+19 and -928/-515, respectively. Furthermore, we have shown that the promoter activity is significantly enhanced by a GHSR agonist in a cell line stably expressing the seabream GHSR, and this stimulatory effect could be completely blocked by a GHSR antagonist. These results suggest that homologous up-regulation plays an important role in the transcriptional control of the teleostean GHSR gene. This is in big contrast to the human situation in which a homologous down-regulation of the GHSR gene transcription by its own ligand has been previously demonstrated.

5' Flanking Region↗
PubMed1997

Longitudinal changes in consensus as a function of acquaintance and agreement in liking.

By using a round-robin design, groups of freshmen reported their impressions of dormmates at 4 different times during the year. Consensus on W. T. Norman's Big Five (1963) did not increase over the year, even though reported acquaintance did increase. Agreement in liking predicted agreement in the trait ratings, such that groups that agreed in their evaluations of one another were more likely to agree in their trait impressions of one another, and vice versa. These patterns, obtained by using trait ratings, were replicated with open-ended descriptions of the targets. Correlations with self-judgments did not increase with acquaintance. The data suggest that increased acquaintance does not produce increased consensus. Instead, the role of agreement in evaluations is explored as a determining factor in the level of obtained consensus.

Cross-Sectional Studies↗
PubMed1995

Endothelin-converting enzyme-2 is a membrane-bound, phosphoramidon-sensitive metalloprotease with acidic pH optimum.

Endothelins (ET) are a family of potent vasoactive peptides that are produced from biologically inactive intermediates, termed big endothelins, via a proteolytic processing at Trp21-Val/Ile22. We recently cloned and characterized a membrane-bound metalloprotease that catalyzes this proteolytic activation, endothelin-converting enzyme-1 (ECE-1) (Xu, D., Emoto, N., Giaid, A., Slaughter, C., Kaw, S., deWit, D., and Yanagisawa, M. (1994) Cell 78, 473-485). This enzyme was shown to function in the secretory pathway as well as on the cell surface. Here we report molecular cloning of another novel enzyme, ECE-2, that produces mature ET-1 from big ET-1 both in vitro and in transfected cells. The cDNA sequence predicts that bovine ECE-2 is a metalloprotease structurally related to ECE-1, neutral endopeptidase 24.11, and human Kell blood group protein. The deduced amino acid sequence of ECE-2 is most similar to ECE-1, with an overall identity of 59%. ECE-2 resembles ECE-1 in that it is inhibited in vitro by phosphoramidon and FR901533 but not by thiorphan or captopril, and it converts big ET-1 more efficiently than big ET-2 or big ET-3. However, ECE-2 also exhibits the following striking differences from ECE-1. (i) The sensitivity of ECE-2 to phosphoramidon is 250-fold higher as compared with ECE-1, while FR901533 inhibits both enzymes at similar concentrations. (ii) ECE-2 has an acidic pH optimum at pH 5.5, which is in sharp contrast to the neutral pH optimum of ECE-1. ECE-2 has a narrow pH profile and is virtually inactive at neutral pH. Chinese hamster ovary (CHO) cells, which lack detectable levels of endogenous ECE activity, secrete mature ET-1 into the medium when doubly transfected with ECE-2 and prepro-ET-1 cDNAs. However, ECE-2-transfected CHO cells do not efficiently produce mature ET-1 when present with an exogenous source of big ET-1 through coculture with prepro-ET-1-transfected CHO cells. These findings suggest that ECE-2 acts as an intracellular enzyme responsible for the conversion of endogenously synthesized big ET-1 at the trans-Golgi network, where the vesicular fluid is acidified.

Amino Acid Sequence↗
PubMed1993

Conversion of big endothelin-1 in rat uterus causes contraction mediated by ETA receptors.

Like endothelin-1 (ET-1), its immediate human precursor big ET-1 (1-100 nM) increased the rate of spontaneous phasic contractions and caused graded tonic contractions of isolated rat uterus strips. The tonic contraction to big ET-1 (10 nM) was markedly blocked by phosphoramidon (100 microM), which did not modify the response to an equipotent concentration of ET-1 (3 nM). Responses to big-ET-1 (30 nM) were abolished in calcium-free medium, but those to ET-1 (10 nM) were only reduced by this condition. The EC50 of big ET-1 for inducing tonic contraction was only sevenfold greater than that of ET-1, and both peptides produced a maximal response similar to that evoked by KCl 80 mM. ET-3 was much less potent. The selective ETA receptor antagonist BQ-123 (40-600 nM) caused graded rightward shifts of the ET-1 curve without affecting the maximal response, yielding a Schild plot with a slope not different from unity and a pA2 value of 7.76. BQ-123 (100 nM) did not affect contractions induced by oxytocin (5 nM), acetylcholine (3 microM), or bradykinin (0.3 nM), but inhibited responses to both big ET-1 and ET-1. Therefore, the rat uterus contains a phosphoramidon-sensitive, calcium-dependent endothelin-converting enzyme that readily converts big ET-1 into ET-1, which then contracts the myometrium via activation of ETA receptors.

Amino Acid Sequence↗
PubMed1997

Safety of long-term administration of granulocyte colony-stimulating factor for severe chronic neutropenia.

When a new product with huge clinical potential explodes on the scene, the hope is that the benefits far outweigh the risks in long-term administration. After 10 years of clinical use, granulocyte colony-stimulating factor (G-CSF) has lived up to that promise so far. In the context of severe chronic neutropenia, more than 90% of patients have reaped big benefits in terms of improved quality of life and less infection, inflammation, antibiotic use, and hospitalization as well as oropharyngeal ulcers. With long-term use, toxic and adverse events have been catalogued but in general are not clinically troublesome and, aside from occasional adjustment of scheduling and dosing, seldom necessitate stopping therapy. Currently, the topic of intense focus is the phenomenon of malignant myeloid transformation in patients with congenital neutropenia who are receiving G-CSF. Data from the Severe Chronic Neutropenia International Registry have identified 23 of 249 patients with congenital neutropenia who have developed myelodysplasia or acute myelogenous leukemia (MDS/AML) giving a crude rate of about 9% with an average follow-up of 4.5 years. No cases of MDS/AML have occurred in 257 patients with cyclic or idiopathic neutropenia. A critical analysis of the incidence of transformation year by year showed a fairly uniform hazard rate of less than 2% per year, and the risk of MDS/AML after 5 to 6 years of therapy did not appear to be greater than during the first year of therapy. The transformation risk in the congenital cohort must also be viewed in the context of published reports of spontaneous myelodysplasia or acute myelogenous leukemia occurring in these patients in the pre-G-CSF era. Thus, the role of G-CSF in malignant conversion is still not clear and requires long-term vigilance and research. G-CSF is still deemed specific therapy for severe chronic neutropenia with a high margin of safety and should be the initial treatment for this family of disorders.

Chronic Disease↗
PubMed2002

A possibility of systematisation of anthropometric data of girls aged 12-15.

The article describes an anthropometric cross-sectional study of 374 healthy schoolgirls aged 12-15 years from secondary schools of Tartu (Estonia). 29 body measurements and 9 skinfolds were measured. Mean skinfolds and 6 indices and ratios (including body mass index) were calculated. In each age group the data were systematized into 5 height-weight SD-classes according to the correspondence between body height and weight. The medium class lies between -0.5 SD and +0.5 SD of the respective age group mean (M +/- 0.5 SD); the other classes contain the respective outer values. All the subjects were assigned into one of the following five categories: three height/weight-concordant categories: I = small (small height-small weight), II = medium (medium height-medium weight), III = large (big height-big weight) and two height/weight-disconcordant categories: IV = so-called pyknomorphous, V = so-called leptomorphous. Categories IV and V thus contained three height/weight subclasses each. The body build categories differ significantly from each other within both groups (I-III and IV-V) in all age groups in all measured variables, except sternum length, abdomen length, trunk length, biacromial breadth, biiliocrystal breadth, femur breadth, ankle breadth, humerus breadth, wrist breadth, and head circumference for which no significant differences between pyknomorphous and leptomorphous categories were found. A multidimensional statistical model of body build might be used in girls going through puberty to systematize and compare morphological variables with other assessed characteristics in different applied studies, for example physiological, sociological, psychological, or nutritional.

Adolescent↗
PubMedDate not supplied

[Is the inhibition of adenosine A(2A) receptors an efficient way of Parkinson's disease treatment?].

The authors intended to focus the attention of the medical community on the potential therapeutic usefulness of A(2A) adenosine receptors antagonists in the treatment of Parkinson's disease. Basal ganglia express a big amount of A(2A) adenosine receptors, occurring mainly on the external surfaces of neurons located at indirect pathways between the striatum, globus pallidus and substantia nigra. Experiments with the animal models of Parkinson's disease indicate that A(2A) receptors are strongly involved in the regulation of the central movement system. Co-localization of A(2A) and dopaminergic D2 receptors in the striatum creates a milieu for an antagonistic interaction between adenosine and dopamine. The experimental data prove that the best mobility improvement of patients with Parkinson's disease could be achieved with a simultaneous activation of dopaminergic D2 receptors and inhibition of adenosine A(2A) receptors. In animal models of Parkinson's disease, the use of selective antagonists of A(2A) receptors, such as istradefylline, led to the reversibility of movement dysfunction. These compounds might improve the mobility during both monotherapy and co-administration with L-dopa and the dopamine receptor agonists. The use of these antagonists in the combined therapy enables the reduction of the L-dopa doses, as well as reduction of the side effects. In the adjunctive therapy, the A(2A) antagonists might be used in both moderate and advanced stages of Parkinson's disease. The long-lasting administration of the A(2A) receptor antagonists does not decrease patient's response and does not cause side effects typical of the L-dopa therapy. It was proved on different animal models that inhibition of A(2A) receptors not only decreases the movement disturbance, but also reveals the neuroprotective activity, which might slow down or stop the progress of the disease.

Adenosine A2 Receptor Antagonists↗
PubMed1978

Declining world fertility: trends, causes, implications.

This Bulletin examines the evidence that the world's fertility has declined in recent years, the factors that appear to have accounted for the decline, and the implications for fertility and population growth rates to the end of the century. On the basis of a compilation of estimates available for all nations of the world, the authors derive estimates which indicate that the world's total fertility rate dropped from 4.6 to 4.1 births per woman between 1968 and 1975, thanks largely to an earlier and more rapid and universal decline in the fertility of less developed countries (LDCs) than had been anticipated. Statistical analysis of available data suggests that the socioeconomic progress made by LDCs in this period was not great enough to account for more than a proportion of the fertility decline and that organized family planning programs were a major contributing factor. The authors' projections, which are compared to similar projections from the World Bank, the United Nations, and the U.S. Bureau of the Census, indicate that, by the year 2000, less than 1/5 of the world's population will be in the "red danger" circle of explosive population growth (2.1% or more annually); most LDCs will be in a phase of fertility decline; and many of them -- along with most now developed countries -- will be at or near replacement level of fertility. The authors warn that "our optimistic prediction is premised upon a big IF -- if (organized) family planning (in LDCs) continues. It remains imperative that all of the developed nations of the world continue their contribution to this program undiminished."

Africa↗
PubMedDate not supplied

Radiation therapy treatment planning using concurrent programming.

Concurrent programming can be applied to the problem of computer graphic simulation of radiation treatment of tumors (radiation treatment planning). Running several tasks or programs simultaneously on behalf of a single user provides a big improvement over the traditional sequential approach, in which editing a treatment plan and computing and displaying dose distributions are separate operations which must be invoked by explicit commands. With our system, the user sees isodose contours being updated automatically and continuously as the plan is edited; this greatly facilitates plan optimization. The complexity of parallel processing has resulted in a 'conventional wisdom' which discourages this technique. The usual approach is to have parallel processes share a common global data structure, which makes interaction hard to control and discourages modularity and data abstraction. We have developed an alternative approach based on message streams which instead enhances modularity and data abstraction while still providing the advantages of parallel processing. The system is very reliable and is used routinely in a practical clinical environment.

Computer Simulation↗
PubMed2006

Desired family size, family planning and fertility in Ethiopia.

This paper models the proximate determinants of children born to over 13,000 Ethiopian women and of the women's stated preferences for additional births using the data from the Ethiopian Demographic and Health Survey 2000. Empirical models for the number of children born to women were estimated using Poisson and ordinal regressions. The results show the importance of variables such as maternal education for smaller family size, and that variables reflecting desired family size are strong predictors of the numbers of children born to women. Secondly, binary logistic models for dichotomous variables for women not wanting more children and if getting pregnant would be a 'big problem' showed non-linear effects of the surviving and 'ideal' number of children. Moreover, the results indicated a desire on the part of women to limit family size, especially as the number of surviving children increased. Probit models were estimated to address potential endogeneity of certain variables. Overall, the results indicated that counselling couples about small family size and increasing the utilization of health care services can lower fertility in Ethiopia.

Educational Status↗
PubMed2001

Inhalation toxicology of urban ambient particulate matter: acute cardiovascular effects in rats.

Wistar rats were exposed for 4 hours by nose-only inhalation to clean air, resuspended Ottawa ambient particles (EHC-93*, 48 mg/m3), the water-leached particles (EHC-93L, 49 mg/m3), diesel soot (5 mg/m3), or carbon black (5 mg/m3). Continuous data for physiologic endpoints (heart rate, blood pressure, body temperature, animal's activity) were captured by telemetry before and after exposure. Blood was sampled from jugular cannulas 1 to 3 days before exposure and at 2 and 24 hours after exposure, and by heart puncture on termination at 32 hours (histology group) or 48 hours (telemetry group) after exposure. Lung injury was assessed by 3H-thymidine autoradiography after the rats were killed. We measured endothelins (plasma ET-1, big ET-1, ET-2, ET-3) to assess the vasopressor components; nitric oxide (NO)-related metabolites (blood nitrate, nitrite, nitrosyl compounds, and plasma 3-nitrotyrosine) to assess the vasodilator components; and catecholamines (epinephrine, norepinephrine, L-DOPA, dopamine) and oxidative stressors (m- and o-tyrosine) for additional insight into possible stress components. Lung cell labeling was uniformly low in all treatment groups, which indicates an absence of acute lung injury. Inhalation of EHC-93 caused statistically significant elevations (P < 0.05) of blood pressure on day 2 after exposure, plasma ET-1 at 32 hours after exposure, and ET-3 at 2, 32, and 48 hours after exposure. In contrast, the modified EHC-93L particles, from which soluble components had been extracted, did not affect blood pressure. The EHC-93L particles caused early elevation (P < 0.05) of the plasma levels of ET-1, ET-2, and ET-3 at 2 hours after exposure, but the endothelins returned to basal levels 32 hours after exposure. Exposure to diesel soot, but not carbon black, caused an elevation (P < 0.05) of plasma ET-3 at 36 hours after exposure; blood pressure was not affected by diesel soot. Our results indicate that inhalation of the urban particles EHC-93 can affect blood levels of ET-1 and ET-3 and cause a vasopressor response in Wistar rats without causing acute lung injury. Furthermore, the potency of the particles to influence hemodynamic changes appears to be modified by removing polar organic compounds and soluble elements. Because the pathophysiologic significance of elevated endothelins has been clinically established in humans, our observations suggest a novel mechanism by which inhaled particles may cause cardiovascular effects. These findings in rats contribute to the weight of evidence in favor of a biologically plausible epidemiologic association between ambient particulate matter and cardiovascular morbidity and mortality in human populations.

Administration, Inhalation↗
PubMed1993

Incomplete inhibition of the pressor effects of endothelin-1 and related peptides in the anaesthetized rat with BQ-123 provides evidence for more than one vasoconstrictor receptor.

1. The effects of the ETA receptor antagonist, BQ-123 on blood pressure changes induced by various members of the endothelin (ET)/sarafotoxin (SX) peptide superfamily were investigated in the anaesthetized rat. 2. ET-1 (1 nmol kg-1, i.v. bolus) induced a sustained increase in mean arterial pressure (MAP, maximum increase 44 +/- 3 mmHg). Intravenous injection of BQ-123 at 0.2, 1.0 or 5.0 mg kg-1 5 min before ET-1 inhibited the pressor response by 18, 50 and 61%, respectively. The ET-1 pressor response was inhibited by 75% when the peptide was given 60 min after the start of a 120 min i.v. infusion of BQ-123 (0.2 mg kg-1 min-1). 3. In addition to ET-1, BQ-123 (1 mg kg-1, i.v. bolus) attenuated the pressor responses to big ET-1 (1 nmol kg-1, i.v., bolus, maximum increase in MAP: 68 +/- 7 mmHg), ET-3 (3 nmol kg-1, i.v., bolus, maximum response: 30 +/- 3 mmHg), SX6b (1 nmol kg-1, i.v., bolus, maximum response: 41 +/- 5 mmHg) and SX6c (1 nmol kg-1, i.v., bolus, maximum response: 24 +/- 4 mmHg) by 65, 60, 88 and 50%, respectively. 4. With the exception of big ET-1, all the peptides used in this study induced an initial transient depressor response (-32 +/- 3 mmHg, n = 18). Although BQ-123 (1 mg kg-1, i.v., bolus) did not affect the absolute magnitude of the fall in MAP, the ETA receptor antagonist significantly prolonged the depressor responses induced by ET-3 and SX6b. 5. Thus, BQ-123 attenuates the pressor, but not the depressor effects of ET-1, big ET-1, ET-3, SX6b and SX6c. Complete inhibition of the pressor responses could not be achieved, suggesting that a component of the pressor response is not mediated via the ETA receptor.

Amino Acid Sequence↗
PubMed2002

A national sampling survey on birth weight in 1998 in China: mean value and standard deviation.

OBJECTIVE: To understand the distribution of live birth weight in China. METHODS: A national survey on live birth weight was performed during July-October, 1998 in China, with stratified sampling. Totally, 22 350 live newborns (11 584 males and 10 766 females) with 28 weeks or more of gestation were measured for their birth weight in the sampling sites during 1998. RESULTS: The ratio of male to female newborns measured was 1.08. The rates of multiple birth and preterm birth (< 37 weeks of gestation) were 1.8% and 3.5%, respectively. Live birth weight was higher in the urban areas (3 301 g) than that in the rural area (3 225 g) (t = 9.4. P < 0.001), the highest in the coastal areas (3 262 g), middle in the inland areas (3 254 g) and the lowest in the remote areas (3 115 g) (F = 177.9, P < 0.001), with a decreasing trend. Live birth weight in the first-class rural areas approximated to that in the urban areas, and that in the second-class, third-class and fourth-class rural areas decreased significantly. The average live birth weight in the fourth-class rural areas was 200 g lower than that in the urban areas. CONCLUSIONS: Generally, the average live birth weight in China was closed to that in the developed countries. But, a big difference in the average live birth weight between regions with varied economic development and health care condition was observed. An intervention measure should be implemented in the poverty-stricken rural areas to increase their average live birth weight.

Birth Weight↗
PubMed2002

Use of every ten-day criteria for metabolic profile test after calving and dry off in dairy herds.

The traditional metabolic profile test cannot be applied to peripartum dairy cows, because these cows are in a state of physiological abnormality making it difficult to interpret their blood components. This study aimed at establishing and evaluating the practicability of interpreting a metabolic profile test every 10 days (Ten-day criteria) during the dry and lactation periods in herds with high and no incidence of peripartum diseases. Data from 29,043 cows in 1,130 commercial dairy herds were used to establish standard values every 10 days, mean +/- 1.0 standard deviation for the metabolic profile test. The practicability of these criteria was evaluated in herds with peripartum diseases. In the ten-day criteria, the body condition score, albumin, blood urea nitrogen, glucose, total cholesterol, nonesterified fatty acids, gamma-glutamyl transpeptidase and aspartate aminotransferase, fluctuated during the dry and early lactation periods and there were very big changes in packed cell volume, blood urea nitrogen, total cholesterol and magnesium just after calving. The ten-day criteria were able to detect overconditioned cows, low levels of albumin, total cholesterol and magnesium, and high nonesterified fatty acids in herds with a high incidence of peripartum diseases. In conclusion, the ten-day criteria can be successfully applied to peripartum cows, and is recommended because it is able to detect metabolic abnormalities not only in the herd, but also in individual cows.

Animal Husbandry↗
PubMed1976

[Influence of rapeseed oil feeding on morphology and oxidative properties of mitochondria isolated from the rat heart].

Mitochondria from heart of rats fed a diet rich in rapeseed oil for two months from weaning, oxidized oleic acid a little better than those from animals fed a control diet containing peanut oil; but their activity decreased much more in presence of potassium cyanide which is an oxidation inhibitor. When observed by electronic microscopy, mitochondria from heart of rats fed rapeseed oil were more mumerous and more mitochondria of great size were encountered as compared with control rats. Biochemical data seemed to show a decrease of activity or quantity of certain enzymatic systems in mitochondria from heart of animals fed rapseed oil. Cyanide could more easily inhibit these enzymatic systems because of their deficiency. It can be thought that it is the mitochondria of great size which are implicated in this phenomenon since their growth is not accompanied by an increase of their content in certain enzymes which are just sensitive to cyanide. A mixture richer in mitochondria of big size, thus poorer in certain enzymes for an equal protein content in drastic conditions, such as partial anoxia since cyanide blocks the respiratory chain.

Administration, Oral↗
PubMed1981

[Treatment results of Hodgkin's disease, stages I and II (author's transl)].

The results obtained in the treatment of Hodgkin's disease, stages I and II, are discussed comparing survival data of the literature after various radiotherapy programs and after combined modality using additional chemotherapy. In stage IA 90 to 97% and in stage IIA 75 to 80% of patients are not prone to relapse after extended-field irradiation. In stage IIB 0 to 80% long-lasting remissions are reported after radiotherapy. Additional chemotherapy improved relapse-free survival, but not overall survival in stages I and II. Subgroups are discussed which bear a high risk of relapsing disease (big mediastinal masses, E-lesions of the lungs, histological findings with lymphocyte depletion).

Antineoplastic Agents↗
PubMed1995

Interlaboratory comparison: liver spontaneous mutant frequency from lambda/lacI transgenic mice (Big Blue) (II).

Spontaneous mutant frequency in livers of two transgenic mouse strains, each carrying identical lambda shuttle vectors with a lacI target gene, was evaluated by two laboratories. These studies investigated variability in spontaneous mutant frequency between animals and as a function of the number of phage screened. Liver DNA was independently isolated from 7-11 week old C57BL/6 and B6C3F1 Big Blue transgenic mice. At least 500,000 phage were screened for mutation at lacI for each animal using standardized assay procedures. In the two labs, the C57BL/6 liver spontaneous mutant frequency was 45 +/- 9 x 10(-6) and 41 +/- 7 x 10(-6). The B6C3F1 liver spontaneous mutant frequency was 42 +/- 10 x 10(-6) at one lab and 43 +/- 12 x 10(-6) and 41 +/- 8 x 10(-6) in two trials at the second lab. Mean mutant frequency data from both labs, calculated in increments of 100,000 plaque forming units (pfu) scored for each mouse strain, show stabilized mean mutant frequency and standard deviation after approximately 200,000-300,000 pfu screened. The frequency of spontaneous lacI mutants was reproducible both within and between labs and was comparable between the two transgenic mouse strains.

Animals↗