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Biomedical subjects

P Ash

Publications and source records attributed to P Ash.

32 records · Page 2Linked to original sources

The influence of radiation on fertility in man.

Increasing numbers of young people are now being cured of certain neoplasms by radiotherapy and chemotherapy. Such people will naturally wish to lead a normal life and possibly to have children. Therefore the question of the effect of radiation and cytotoxic drugs on the reproductive capacity of these patients has become important. The purpose of this report is to review the information available on the effect of radiation on fertility in man. Direct information on radiation effects on human fertility is available from reports on therapeutic exposure and deliberate experimental exposure. Although the total number of cases involved is small, a number of general principles emerge. In males, fractionated irradiation of the testes may be more harmful than acute, at least up to total doses of about 600 cGy (rad). Fractionated doses greater than 35 cGy cause aspermia, the time taken for recovery increasing with dose, and after more than 200 cGy aspermia may be permanent. In females, response varies with age as well as dose. For example, 400 cGy may cause a 30% incidence of sterility in young women, but in women aged above 40 years it results in 100% sterility. However, individuals of either sex show a degree of variation in their response to irradiation.

Adolescent↗

The ultrastructure of mouse testicular interstitial tissue containing plutonium-239 and its significance in explaining the observed distribution of plutonium in the testis.

The technique of autoradiography with Araldite-embedded sections was used to study the distribution of 239Pu in mouse testis at various times post-injection. Adjacent sections were examined with both the light microscope and electron microscope. The autoradiographs showed that from 1 week to 3 months postinjection, most 239Pu in located in interstitial tissue. The major change in distribution observed was that the early diffuse deposit in interstitial tissue is concentrated in macrophages with increasing time post-injection. This is a real change of distribution as the amount of 239Pu in mouse testis remains constant from 1 week to 3 months post-injection. Study of the ultrastructure of interstitial tissue indicated that the accumulation of 239Pu in macrophages may be brought about in two ways. First, there may be phagocytosis of dead cells containing 239Pu. Second, 239Pu may follow the transfer of waste products of hormone synthesis from Leydig cells into macrophages. The significance of these observations is discussed with regard to the deposition of 239Pu in human testis.

Animals↗

The ultrastructure of skeletal haemangiosarcomas induced in mice by strontium-90.

The commonest skeletal tumour occurring in male CBA and C3H mice injected with 7--13 muCi 90Sr (per mouse) at Harwell was diagnosed with the light microscope as haemangiosarcoma. On the other hand, Nilsson, using male CBA mice injected with similar amounts of 90Sr, recorded the predominant tumour as fibroblastic osteosarcoma. To resolve the apparent discrepancy, samples of non-osteogenic tumours induced by 90Sr at Harwell were examined with the electron microscope and their ultrastructure compared with that described for fibroblastic osteosarcoma by Nilsson. The tumours diagnosed as haemangiosarcoma at Harwell showed ultrastructural features not observed in the fibroblastic osteosarcomas. Vasoformation was marked, the vascular channels varying in shape, size and in the character of their lining cells. Some vascular channels were lined by cuboidal cells, crowded together, and surrounded by a basement membrane. Others were lined by an attenuated endothelium and often formed networks. The tumour cells showed great variation in shape, size and ultrastructure and were sometimes enclosed by a basement membrane. Thus the ultrastructure of the tumours described in this report supports the diagnosis of haemangiosarcoma, rather than fibroblastic osteosarcoma. The question of whether these haemangiosarcomas truly originate from vascular endothelium, or are mimics, is discussed.

Animals↗

Response of isoalted rabbit articular and epiphyseal chondrocytes to rat liver somatomedin.

Isolated rat liver, when perfused with medium containing bovine growth homone produced somatomedin-like activity (liver somatomedin). Liver somatomedin is useful in studies of the hormonal control of the cartilage plate in vitro, since unlike serum it is not contaminated with other hormones or growth factors (apart from growth hormone). Chondrocytes isolated from various regions of the growth cartiage responded differently to liver s-omatomedin; proliferative chondrocytes, like those isolated from the articular cartilage, showed increased [3H]thymidine uptake in response to liver somatomedin, whereas hypertrophic chondrocytes did not respond. It is suggested that there is a reduction in the response to somatomedin by growth plate chondrocytes as they pass from the proliferative to the hypertrophic state. Thyroxine, thought to be involved in thr processes of hypertrophy and new bone formation, did not directly affect [3H]thymidine uptake by proliferative chondrocytes, but inhibited stimulation of both their activity by liver somatomedin. Mesurement of [3H]thymidine uptake by isolated articular chondrocytes may provide a useful assay for both liver and serum somatomedin. The graded response of chondrocytes to increasing concentrations of liver somatomedin paralleled the response to increasing levels of serum somatomedin.

Animals↗

Osteoclasts derive from hematopoietic stem cells according to marker, giant lysosomes of beige mice.

To ascertain the origin of multinucleated osteoclasts from hematopoietic stem cells, giant lysosomes peculiar to cells of beige mice (bg bg) were used as marker cells of that provenance. Radiation chimeras were established reciprocally between bg bg mice and osteopetrotic mi mi mice with defective osteoclasts. As a result, all the derivative cells of the hematopoietic stem cell would depend on the donor's cell line, whereas osteogenesis would remain the province of the host. It was affirmed in the chimeras mi mi/bg bg that the osteopetrosis was cured within six weeks. Thereafter the definitive osteoclasts of the chimeras contained giant lysosomes attributable to the beige cell line. However, the cure was well advanced before donor osteoclasts were prominent, for which several reasons are offered. In the mouse chimeras, bg bg/mi mi, there was a delay of some six weeks before osteopetrosis became evident, histologically before radiologically, at the major metaphyseal growth centers. During the period one to two months after establishment, osteoclasts appeared to be a mixture of two cell lines according to quantitative assessments for giant lysosomes. Assessments consisted of measurements of the percentage area of osteoclasts occupied by lysosomes over 1 micrometer diameter. The means were 0.018% +/- 0.008% for nonbeige stock and 2.09% +/- 0.58% for beige stock.

Animals↗