Distribution of sister chromatid exchanges in different types of chromatin in the X chromosome ofMicrotus cabrerae

We used the X chromosomes ofMicrotus cabrerae as a model to analyze the distribution of sister chromatid exchanges (SCEs) on different types of chromatin, because of the marked heterogeneity of the heterochromatin in the entire short arm and a portion of the long arm of this chromosome. Computer-simulated distributions, according to an algorithm that makes it possible to modify the distribution on the basis of any possible hypothesis, were compared with real distributions by log-linear models. We found that the frequency of SCEs in different types of heterochromatin was higher than that expected for a random distribution, and located an SCE hot-spot at the junction between euchromatin and heterochromatin. The possible relationship between the distribution of SCEs and base composition or chromatin accessibility are discussed.     

Mitotic response and sister chromatid exchanges in lymphocytes cultured in sera from different sources

Summary The numbers of sister chromatid exchanges in lymphocytes grown in varying concentrations of serum from different sources indicated that some sera contain a factor, probably introduced as a contaminant, which induces SCEs. Sera from 6 animals showed no evidence of a difference in baseline SCE levels due to the donor of the serum.Research sponsored by U.S. Department of Energy contract number DE-ACO5-760R00242 with The University of Tennessee.     

Induction of sister chromatid exchanges in vivo in bone marrow cells of AKR mice]

Induction of sister chromatid exchanges (SCEs) in bone-marrow cells of AKR Mice receiving in vivo four drugs well-known for their mutagenesis activity has been tested. A decreasing activity in SCE was shown by the drugs tested in the order cyclophosphamide, procarbazine, methylmethane sulfonate and diethylnitrosamine. This technique presents an encouraging method for testing the effect of chemical agents in vivo.     

Evidence for a role of IFN gamma in control of Listeria monocytogenes in T cell deficient mice.

The role of interferon (IFN) gamma in controlling chronic infections of Listeria monocytogenes (Listeria) was studied in athymic C57BL/6 nu/nu mice, and by treating thymectomized C57BL/6 +/+ mice with monoclonal rat CD4 and CD8-specific monoclonal antibodies (Mab). Mice treated with a combination of the two T cell subset antibodies were similar to athymic, nude mice in being able to control Listeria infection, keeping the titers below 3-5 log10 bacteria per organ, but they could not eliminate them completely. Treatment with antibodies to IFN gamma of nude or CD4+ + CD8+ - T cell-depleted mice suffering from chronic Listeria infection caused a marked increase of Listeria titers in liver and spleen. This result implies a role of IFN gamma in maintaining anti-Listeria resistance in mice lacking mature T cells.     

Prolongation of the survival of skin grafts in mice by PUVA treatment

The combined application of psoralen and UVA radiation to skin grafts induced a prolongation of the survival time of the grafts in mice. This was observed using the H-Y barrier, an allogeneic barrier without H-2 disparities, and a strong H-2 incompatible barrier. The effect is probably due to a reduction of antigen-presenting cells, or to other, unknown mechanisms.     

Mast cells in the pinna of Balb/c 'nude' (nu/nu) and heterozygotes (ny/+)mice.

The relative number of mast cells in the ear lobes' skin (pinna) of nude (athymic) nu/nu and normal (thymic) nu/+ heterozygotes of Balb/c mice was similar. The results obtained contradict some suggestions about the general influence of the thymus on the number of mast cells in the skin and suggest the existence of some local factor(s) in regulation of skin mast cell numbers.     

Prolongation of the survival of skin grafts in mice by PUVA treatment

Summary The combined application of psoralen and UVA radiation to skin grafts induced a prolongation of the survival time of the grafts in mice. This was observed using the H-Y barrier, an allogeneic barrier without H-2 disparities, and a strong H-2 incompatible barrier. The effect is probably due to a reduction of antigen-presenting cells, or to other, unknown mechanisms.     

Digestive enzymes in the gut and salivary gland of the larvae ofChilo auricilius Ddgn.

Summary Amylase, - and -glucosidase, - and -galactosidase, -fructosidase, trypsin, aminotripeptidase, leucine-aminopeptidase, prolinase, prolidase glycyl-L-leucine dipeptidase and glycylglycine dipeptidase are present in the 3rd instar larvae ofChilo auricilius.Dr Kishan Singh, Indian Institute of Sugarcane Research, Lucknow, is gratefully acknowledged for providing necessary facilities.     

Mast cells in the pinna of Balb/c ‘nude’ (nu/nu) and heterozygotes (nu/+) mice

Summary The relative number of mast cells in the ear lobes' skin (pinna) of nude (athymic) nu/nu and normal (thymic) nu/+ heterozygotes of Balb/c mice was similar. The results obtained contradict some suggestions about the general influence of the thymus on the number of mast cells in the skin and suggest the existence of some local factor(s) in regulation of skin mast cell numbers.This work was supported by grant No. CA16426.The author wishes to thank Dr Kenneth Morrison for supplying the mice and the discussion, Mr Duffy Michowski for taking care of the animals used, Mr Carl Polley for taking the pictures and Dr N. R. Rose for the discussion.     

The role of p53 in tumour suppression: lessons from mouse models

The use of mouse models has greatly contributed to our understanding of the role of p53 in tumour suppression. Mice homozygous for a deletion in the p53 gene develop tumours at high frequency, providing essential evidence for the importance of p53 as a tumour suppressor. Additionally, crossing these knockout mice or transgenic expression p53 dominant negative alleles with other tumour-prone mouse strains has allowed the effect of p53 loss on tumour development to be examined further. In a variety of mouse models, absence of p53 facilitates tumorigenesis, thus providing a means to study how the lack of p53 enhances tumour development and to define genetic pathways of p53 action. Depending on the particular model system, loss of p53 either results in deregulated cell-cylce entry or aberrant apoptosis (programmed cell death), confirming results found in cell culture systems and providing insight into in vitro function of p53. Finally, as p53 null mice rapidly develop tumours, they are useful for evaluating agents for either chemopreventative or therapeutic activities.     

An epoxidation byCorynebacterium simplex

Zusammenfassung Während unserer Untersuchungen über die mikrobiologische Dehydrierung verschiedener 16-Methylsteroide durch Bakterienkulturen vonCorynebacterium simplex, wurde eine neue Art von Umwandlung beobachtet. Von 16-Methyl-9(11)-pregnen-17, 21-diol-3, 20-dion-21-acetat ausgehend, gelang es aus den Kulturfiltraten 16-Methyl-1, 4-pregnadien-9, 11-epoxy-17, 21-diol-3, 20-dion zu isolieren. In einigen Fällen wurde auch das4-Derivat dieser Verbindung als Nebenprodukt erhalten.     

Mitogenicity of autolysates of Trypanosoma congolense

Autolysates of Trypanosoma congolense, in subcytotoxic amounts, were found to be highly mitogenic in vitro for the spleen cells of normal mice. Significant amounts of [3H]-thymidine were also incorporated by the responding spleen cells of nu/nu (athymic) mice. In contrast, the spleen cells of cyclophosphamide-treated mice were unresponsive. The findings suggest that a potent B-cell-mitogen is generated by the autolysing T. congolense organism.     

Studies on lipid peroxidation using whole liver cells: Influence of damaged cells on the prooxidant effect of ADP-Fe3+ and CCl4

Summary An increase in the number of damaged cells produces an enhancement of lipid peroxidation induced by ADP-Fe³⁺ or CCl₄ in vitro on hepatocytes in single cell suspension.This work has been supported by the Consiglio Nazionale delle Ricerche, Roma, Italy, and the National Foundation for Cancer Research, Bethesda, Maryland, USA.     

Hyperprolactinemia and estrogen-induced rhythms in LH and prolactin release in the ovariectomized rat

Summary Short-term (9 days) hyperprolactinemia induced by pituitary grafts reduced basal plasma LH levels in ovariectomized rats whereas long-term (31 days) grafts increased basal LH levels. Although long-term grafts inhibited estradiol-induced prolactin surges, hyperprolactinemia had no effect on the LH surge. It is concluded that the estrogen-treated ovariectomized rat is not suitable for studying the effects of hyperprolactinemia on LH release.     

Ovarian stimulation by exogenous gonadotrophins in fetal ethanol-exposed immature rats

Adult pregnant rats were given either an ad libitum liquid diet containing 5% ethanol, a pair fed liquid diet or an ad libitum diet of rat chow and water administered throughout pregnancy and during the nursing period. The female offspring received either pregnant mare's serum gonadotrophin (PMSG) or PMSG followed by human chorionic gonadotrophin (hCG) at 30 days of age. The ovaries of fetal ethanol-exposed animals responded greater to the exogenous gonadotrophins with enhanced ovarian weights, increased numbers of ova shed, greater numbers of corpora lutea and antral follicles, and higher serum progesterone levels than in animals exposed to the control diets during gestation.     

Hyperprolactinemia and estrogen-induced rhythms in LH and prolactin release in the ovariectomized rat

Short-term (9 days) hyperprolactinemia induced by pituitary grafts reduced basal plasma LH levels in ovariectomized rats whereas long-term (31 days) grafts increased basal LH levels. Although long-term grafts inhibited estradiol-induced prolactin surges, hyperprolactinemia had no effect on the LH surge. It is concluded that the estrogen-treated ovariectomized rat is not suitable for studying the effects of hyperprolactinemia on LH release.     

Hydrogen bond catalysis of mononucleotide ethylation supports non-random DNA alkylations by N-ethyl,N-nitrosourea

Summary The axial (ax.) and equatorial (eq.) diastereomeric forms of phosphate triesters resulting from reactions of N-ethyl, N-nitrosourea with 3 cyclic mononucleotides were analyzed by column liquid chromatography (CLC). Evidence is presented that the 2OH group of 3, 5cAMP essentially contributes to the stereoselective eq. alkyl substitution, most probably by hydrogen bonding catalysis. The neighboring group direction of ethylation gives substantial support to non-random DNA alkylations by NEU.We acknowledge the helpful cooperation of Dr Fritz Eckstein, M.P.I. for Exp. Medicine, Göttingen, who determined the³¹P-N.M.R. spectra of the diastereomeric forms of the neutral ethylester of 3, 5 cAMP. This work has been supported by a personal grant to one of us (Sta 131/6 PAN) from the Deutsche Forschungsgemeinschaft. Reprint requests to K.-W. Stahl.     

Expression of the anti-apoptotic gene survivin correlates with taxol resistance in human ovarian cancer

Stable transfection of human ovarian carcinoma cells with survivin cDNA caused a four- to sixfold increase in cell resistance to taxotere and taxol (two-sided Student's t test, p < 0.05), with a concomitant reduction in the apoptotic response to taxol, but did not affect cell sensitivity to cisplatin or oxaliplatin. Such findings were indirectly supported by similar observations obtained with clinical tumours. In fact, high levels of survivin protein expression (>30% positive cells), detected by immunohistochemistry in 90/124 (73%) advanced ovarian carcinomas, were significantly associated with clinical resistance to a taxol/platinum-based regimen but unrelated to tumour shrinkage following cisplatin-including combinations (non-taxol based). In the 95 patients receiving a taxol/platinum-based regimen, survivin overexpression correlated with a lower clinical or pathologic complete remission rate than absent/low protein expression (43 vs 75%, p = 0.0058 by logistic regression adjusted for tumour stage, histological grade and p53 expression). Conversely, in the 29 cases treated with cisplatin-containing regimens (not taxol based), survivin expression was unrelated to tumour response. Cellular studies and clinical data suggest a direct link between survivin expression and tumour cell susceptibility to taxol.     

Engineering of arteries in vitro

This review will focus on two elements that are essential for functional arterial regeneration in vitro: the mechanical environment and the bioreactors used for tissue growth. The importance of the mechanical environment to embryological development, vascular functionality, and vascular graft regeneration will be discussed. Bioreactors generate mechanical stimuli to simulate biomechanical environment of arterial system. This system has been used to reconstruct arterial grafts with appropriate mechanical strength for implantation by controlling the chemical and mechanical environments in which the grafts are grown. Bioreactors are powerful tools to study the effect of mechanical stimuli on extracellular matrix architecture and mechanical properties of engineered vessels. Hence, biomimetic systems enable us to optimize chemo-biomechanical culture conditions to regenerate engineered vessels with physiological properties similar to those of native arteries. In addition, this article reviews various bioreactors designed especially to apply axial loading to engineered arteries. This review will also introduce and examine different approaches and techniques that have been used to engineer biologically based vascular grafts, including collagen-based grafts, fibrin-gel grafts, cell sheet engineering, biodegradable polymers, and decellularization of native vessels.