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It has previously been reported that 19% of the daughters of males carrying the X-linked mutation patchy fur (Paf) are XO with a maternally derived X chromosome. We now report that hemizygous Paf males that also carry the variant Y chromosome Y*, show a much increased XO production (∼40% of daughters). We hypothesize that the Paf mutation is associated with an inversion spanning the pseudoautosomal region (PAR) boundary, and that this leads to preferential crossing over between the resulting inverted region of PAR and an equivalent inverted PAR region within the compound Y* PAR. This would lead to the production of dicentric X and acentric Y products and consequent sex chromosome loss. This interpretation is supported by analysis of the sex chromosome complements at the second meiotic metaphase, which revealed a high incidence of dicentrics. Another curious feature of the Paf mutation is that mice that are homozygous Paf have more hair than mice that are hemizygous Paf. This can be explained if the Paf mutation is a hypomorphic mutation that escapes X inactivation because, unlike the wild type allele, it is now located within the PAR.

Single cell clones were isolated from the human teratoma line, Tera-2. The cells of three of these clones were studied. The progressively growing cells were shown to be tumorigenic, and they were characterized by the lack of expression of β 2β2-microglobulinand HLA-A,B,C determinants on the cell surface. The majority of the cells expressed Thy-1 antigen and a 90 × 103 molecular weight protein recognized by the monoclonal antibody F10.44.2; between a third and half of the cells expressed the sugar specificities detected by the anti-SSEA-1 monoclonal antibody. In response to 5 × 10−5 M-retinoic acid applied to cells in monolayer culture, the cells differentiated into a population of flat static cells arrested in the GI phase of the cell cycle. A substantial proportion of these differentiated cells expressed β 2-microglobulin and 43 × 103 molecular weight HLA-A,B,C polypeptides, Thy-1, SSEA-1 sugar determinants, and the 90 × 103 protein recognized by F10.44.2. The apparent molecular weight of fibronectin secreted by the cells decreased by about 5 × 103Mr to 235 × 103Mr after differentiation. The progressively growing cells lacked reactivity with reagents that mark cells in the nervous system. Following aggregation and retinoic acid treatment, neuron-like cells were formed. These cells reacted with reagents that also react with human neurons in culture: they reacted with tetanus toxin, the anti-neurofilament antibodies BF10 and RT97, the anti-ganglioside, GQlc antibody F12 A2B5, and anti-Thy-1. The progressively growing cells of these Tera-2 clones are therefore capable of forming at least two types of cell: the flat cells in monolayer cultures and the neuron-like cells. None of the cell populations reacted with the monoclonal antibody against SSEA-3 and these cloned cells are therefore distinct from previous isolates from Tera-2.

Marker chromosome analysis of 18 tetraparental AKR↔CBA/H-T6 chimaeras revealed a great excess of AKR mitoses over CBA mitoses in direct preparations from lymphomyeloid tissues, corneal epithelium, intestinal epithelium and skin (Table 1). The degree of AKR dominance was strongly influenced by anatomical site (Tables 2 and 3). The testes of three out of four XY/XY males contained a marked excess of AKR germ cells and produced a parallel excess of functional AKR gametes (Table 4). Mitotic spreads in mitogen-stimulated cultures of tail blood were overwhelmingly of AKR type in 1972, but less so in 1973 (Table 5). The coat phenotypes, and breeding results from known or presumptive XX/XX females, suggest that AKR and CBA cells were numerically balanced when melanoblasts and oocytes were formed during embryonic development, and therefore that the striking deviations from equality observed in mitotic populations of adult chimaeras arose later by differential proliferation or survival of AKR cells, or both. The low frequency of lymphomas, compared with normal AKR mice, previously reported in these chimaeras cannot therefore be accounted for by insufficiency of AKR cells in the thymus or elsewhere in the lymphomyeloid tissues. One of three lymphomas studied was CBA type. This suggests that the high risk of lymphomatous transformation is not an autonomous property of AKR cells.

SummaryTo determine whether sarcomata of bone are derived from osteo-progenitive cells committed to bone production or from uncommitted pluripotent cells in bone-marrow, radiation chimaeras were injected intraperitoneally with 20 µCi of strontium-90. Both syngeneic CBA/CBA-T6T6 and allogeneic CBA-T6T6/A chimaeras were used. The resulting tumours were analysed cytologically for T6 chromosomes to determine whether they were of host or donor origin. The aneuploid cells of all 13 tumours analysed were of host-type: this was confirmed by genetic analysis in six tumours arising in allogeneic chimaeras.Euploid mitotic cells of donor marrow provenance were commonly seen in preparations of tumours.Tumours were also analysed in 11 of 14 normal mice, both CBA and CBA-T6T6, injected with 20 µCi of strontium-90. No false positive or false negative results for T6T6 were recorded.The bone-tumours were of at least two types, typical osteoblastic sarcomata and osteolytic sarcomata either fibroblastic or haemangioendotheli...

Radioactive adenosine diphosphate (ADP-8-14C) and adenosine triphosphate (ATP-8-14C) were incubated with normal and uraemic plasma and their derivatives were detected and quantitated by thin-layer radiochromatography. In both normal and uraemic plasma ADP was broken down to AMP, adenosine and inosine but the presence of platelets had a retarding effect. ADP breakdown was impaired in uraemic plasma. In normal platelet-rich plasma the amount of adenosine formed correlated with the amount of ADP degraded but this relationship did not hold in renal failure possibly due to increased platelet adenosine uptake. The defective ADP breakdown in uraemic plasma was not related to the biochemical changes which occurred or to the degree of impairment of platelet aggregation. The results indicated that impaired plasma catabolism of ADP was associated with, but did not necessarily cause, defective platelet aggregation in chronic renal failure.

The effect of dose-rate on the induction of reciprocal translocations in mouse A type spematogonia by 600 RX- and γ-irradiation was studied by scoring multivalent configurations in descendant spermatocytes. With X-irradiation over a range of dose-rates from 0.8 to 913 R/min there was no significant change in the frequency of affected spermatocytes, which averaged 12.8%. With γ-irradiation, however, there was a steady increase in frequency from 1.4% at 0.02 R/min to 12.1% at 86 R/min, the points fitting a straight line on a semi-log plot. At 0.08 R/min the X-ray yield was twice that for γ-rays. Possible reasons for these differences are discussed. Frequencies of 0, 1, 2 translocations per spermatocyte did not fit a Poisson distribution since there were less then expected in the 1-class, but more in higher classes. This was probably a consequence of differential radiosensitivity of the irradiated spermatogonia, although preferential clonal proliferation may also be involved.

Small mammals can survive cooling to o°, at which temperature their tissues are virtually anoxic. Thus hypothermia provides a method for studying the role of oxygen tension differences in determining genetic radiosensitivity of different mammalian germ-cell stages. Male mice were given 600 rad acute X-irradiation when hypothermic or at normal body temperature. In mice irradiated when hypothermic the yield of dominant lethal mutations from treated spermatozoa was slightly but not significantly reduced, while the incidence of cytologically identifiable reciprocal translocation configurations in primary spermatocytes derived from irradiated A type spermatogonia was halved (8.3% instead of 17.1%). The usual post-radiation sterile period after 600 rad was abolished in the males made hypothermic and the testis weights showed less reduction than in those given X-rays alone. This evidence for the protection of spermatogonia from somatic and genetic radiation injury by hypothermia shows that oxygen tension differences are important in determining the extent of both types of damage in these immature germ cells. With mature germ cells, however, these and previous findings agree in showing that hypothermia or other methods of oxygen deprivation provide little if any protection from genetic radiation damage to spermatozoa, presumably because they are normally hypoxic.

The study of a bovine freemartin and its male co-twin has shown that the sex-reversed gonads of the female are secreting testosterone. Therefore, we suggest that the masculinisation of the freemartin’s reproductive tract may be due to sex hormones secreted by its own gonads, rather than by those from its male co-twin. On the evidence at present available, we favour the view that the female gonad is sex-reversed by a humoral inductor substance coming from the male co-twin that causes retention of the medullary sex cords. A study of the male co-twin suggests that its gonads may also be abnormal in that they secrete reduced amounts of androgen. Both twins showed extensive 60, XX/60, XY chimaerism, with a metacentric marker chromosome associated with the XY cell line only. This was derived from the dam. The proportion of XY cells varied markedly between tissues in both the twins. We were unable to find any germ cells in the female gonad, and, with the exception of one possible female pachytene, all the germ cells examined in the male’s testes were XY.

The rate of platelet aggregation with adenosine diphosphate was measured in platelet-rich plasma of healthy individuals and compared with the levels of plasma-fibrinogen. Within the physiological range the lower fibrinogen levels were associated with faster rates of platelet aggregation. Low-normal levels of plasma-fibrinogen may not therefore necessarily protect against platelet aggregation (and, hence, thrombosis).