PubMed Health⌕ Search

Biomedical subjects

J Bigda

Publications and source records attributed to J Bigda.

29 records · Page 2Linked to original sources

[Activity of NK in elderly people].

Optimally healthy elderly persons, selected according to Senior Protocol criteria, aged 60-93 years were characterized by as high level of NK activity as their young adult, 20-35 years old, counterparts. NK activity of the nearly optimally healthy elderly persons of the corresponding age was significantly lower than that of optimally healthy ones. The lowest values of NK activity were noted for the elderly persons suffering from recurring infections of the respiratory tract.

Aged↗

Natural killer sensitivity of four Bomirski melanoma variants.

The sensitivity of four hamster melanoma variant cells to natural killer (NK) cell lysis mediated by hamster blood and spleen mononuclear cells is examined. The melanoma variants differed in their differentiation level, growth rate, and frequency and localization of metastases. The cells of the melanoma variants were found to differ in their sensitivity to NK cell mediated lysis. A consistent relationship between high sensitivity to lysis and such tumor characteristics as low differentiation level, slow growth rate, low metastatic potential was not observed.

Animals↗

The natural history of a family of transplantable melanomas in hamsters.

We have characterized a family of transplantable melanomas in Syrian (golden) hamsters, which originated in 1959 as a spontaneous melanoma of hamster skin, and which has been maintained since then by serial passage. Emphasis has been placed on using the same method of transplantation, keeping strict records on all passages, and applying the same investigative techniques, in order to trace tumor behavior over long periods of time. This tumor family consists of five variants linked by common origin, but which differ with respect to differentiation level, malignancy, intermediary metabolism, chromosome number, and cell surface properties. Once established, these melanomas possessed a considerable degree of phenotypic stability over decades of passaging. One tumor line in this family is emphasized. The Ab amelanotic melanoma lost its differentiated functions (the ability to synthetize melanin) a quarter of a century ago, and since then has remained dedifferentiated in serial passage in hamsters. After transfer to primary cell culture, the Ab melanoma cells differentiate readily and lose much of their proliferative potential. This process is reversible by reimplantation of the cells into a hamster. Inasmuch as this hamster melanoma system meets many of the conditions required for an experimental tumor model, five melanoma variants are characterized concisely and compared to other melanomas in humans and animals. Mechanisms by which new melanoma variants arise are discussed and compared to some phenomena in the evolution of the species.

Animals↗

Activity of acid phosphatase in target binding cells expressing NK cytotoxic potential.

Activity of acid phosphatase was analysed in the NK-effectors from human blood forming conjugates with K 562 cells. Presence of activity of acid phosphatase was associated with the cytolytic potential of the NK-effectors. The non-lytic target-binders did not express activity of this enzyme. The results suggest that activity of acid phosphatase in the effector cells of NK reaction is important in the lethal hit stage.

Acid Phosphatase↗

Natural killer sensitivity of tumor cells isolated from primary and metastatic lesions of four Bomirski melanoma variants.

Natural killer (NK) sensitivity of melanoma cells isolated from primary and metastatic lesions of four Bomirski melanoma variants was compared. The hamster melanomas differed in their growth rate and metastatic pattern. We found that during tumor growth of all the variants tested, NK sensitivity of melanoma cells at the metastasis formation stage was significantly lower in both primary and metastatic tumors than in cells isolated from primary tumors at transplantation. In the case of Ma, Ab and Ab-455, NK sensitivity of primary tumor cells was higher than that of the cells isolated from metastatic deposits. These data obtained from a spontaneous metastasis tumor model argue for the role of NK cells in preventing metastatic spread of Bomirski melanomas studied.

Animals↗

Elderly high NK responders are characterized by intensive proliferative response to PHA and Con A and optimal health status.

In this paper we verify a hypothesis emerging from recent immunogerontological studies assuming that an elevated level of NK activity in the elderly may be regarded as a factor compensating for a decreased reactivity of T cells. According to this assumption a high NK activity should be associated with a poor reactivity of T cells. In our study the mitogenic responses of lymphocytes of the elderly and the young high and low NK responders to phytohemagglutinin (PHA) and Concanavalin A (Con A) were measured. A high level of NK activity was not found, as would be expected from the hypothesis, to be associated with a poor reactivity to PHA and Con A. In contrast, the mitogenic response to PHA and Con A was intensive in both the young and old high NK responders while weak proliferative responses to T cell mitogens were characteristic of the young and old low NK responders. Thus, our results do not support the assumption of an association between a high NK activity and a low proliferative response to T cell mitogens in the elderly. We also found that both the elderly and the young high NK responders were characterized by an optimal health status.

Journal Article↗

Synergistic effect of the angiogenesis inhibitor TNP-470 and tumor necrosis factor (TNF) on Bomirski Ab melanoma in hamsters.

Bomirski Ab transplantable melanoma bearing hamsters were treated with angiogenesis inhibitor TNP-470 or with rat tumor necrosis factor (TNF) at doses of 20 micrograms and 40 micrograms or with both TNP-470 and TNF at a dose of 20 micrograms each. The size of the growing tumor was measured everyday from the day when it was palpable. After the death of the animals the final size of their tumors was measured and the number and localisation of metastasis were determined. It was found that the rate of tumor growth was lowest in the group of animals treated with TNF at a dose of 40 micrograms and in the group of animals treated with TNP-470 and TNF at a dose of 20 micrograms. The frequency of metastasis was different in the experimental groups although their location was similar. The longest living animals belonged to the group treated with both TNP-470 and TNF. The results of the investigation indicate that TNP-470 and TNF act in a synergistic way that allows a decrease in the effective dose of TNF thus diminishing its noxious side effects.

Angiogenesis Inhibitors↗

Modification of mitogenic response to concanavalin A of lymphocytes from old-aged donors by ion channel blockers.

Mitogenic response of lymphocytes from young and old donors to Concanavalin A in the absence or presence of Na+ channel blocker--saxitoxin--was compared. Effect of Ca++ channel blockers (Verapamil Diltiazem) on mitogenic response of lymphocytes from old subjects was also examined. It was found that the mitogenic response to Concanavalin A of lymphocytes from donors was significantly lower than that of young ones. In the presence of Saxitoxin the enhancement of the response was noticeable in both groups and the mean responses were similar. However, among the old donors, opposite to the young ones, very high and very poor responders were present. Verapamil and Diltiazem caused significant reduction of mitogenic response to Concanavalin A in the group of old donors. These observations suggest a possible effect of ion channel blockers on immunological functions which would have special significance for old organisms.

Adult↗

Indomethacin inhibits kidney metastasis in bomirski melanoma-bearing hamsters, and modulates natural killer cytotoxic activity of tumor hosts in vivo and in vitro.

Natural killer (NK) cells are thought to play an important role in the control of metastatic dissemination. Therefore, stimulation of cytotoxic activity of NK cells against neoplastic cells could be preventive for metastatic spread. Bomirski amelanotic (Ab) melanoma of Syrian hamster is a transplantable tumor metastasizing preferably to the kidneys. During growth of the melanoma a significant depression of cytotoxic activity of NK cells of tumor hosts is observed. Treatment of melanoma-bearing hamsters with indomethacin provided in drinking water resulted in the increase of NK cytotoxic activity of blood cells and in the lower occurrence of kidney metastasis. Spleen cells obtained from healthy and melanoma-bearing hamsters were cultured in vitro with agents influencing NK activity. We found an augmentative effect of human interleukin 2 (IL2) and human tumor necrosis factor (TNF). We also observed the synergistic effect of IL2/TNF combination, which was present in both groups of animals. The stimulatory effects of cytokines could be potentiated by the additional supplementation of cultures with indomethacin. Similar experiments were performed on spleen cells isolated from the healthy and tumor-bearing animals treated in vivo with indomethacin. Also, in this group of hamsters in vitro stimulation of NK cell activity by the cytokines was effective. The studies presented may give insight into the pathogenesis of immune abnormalities seen in advanced stages of progression of Ab melanoma, and can provide an experimental basis for immunomodulation in this tumor model of spontaneous metastasis.

Animals↗