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Biomedical subjects

F Spencer

Publications and source records attributed to F Spencer.

69 records · Page 4Linked to original sources
PubMed1978

Lack of correlation between in vivo rejection of syngeneic fibrosarcomas and in vitro non-specific macrophage cytotoxicity.

Two transplantable, highly immunogenic syngeneic C57BL fibrosarcomas, FS1 and FS6, were shown to have tumour-specific rejection antigens, as shown by excision of the primary tumours and i.p. or i.m. injection of graded doses of the specific and unrelated tumour cells. I.p. challenge with tumour cells induced a large and relatively long-lasting increase in numbers of peritoneal leucocytes. Macrophage monolayers prepared from such exudates were, in general, non-specifically cytotoxic, though occasional specific cytotoxicity was detected. T lymphocytes isolated from exudates were shown to kill in a specific manner. When immunized mice were challenged with the specific tumour cells to elicit large numbers of peritoneal cytotoxic cells, and with graded doses of the non-cross-reacting tumour cells at the same time or at various times thereafter, growth of the non-related tumours occurred in all cases and only the specific tumour was rejected. Moreover, Winn tests, in which the inflammatory cells were mixed with unrelated tumour cells and implanted i.m., did not delay tumour growth. The relevance of these findings to the role of macrophages and lymphocytes in syngeneic tumour rejection is discussed.

Animals↗
PubMed1976

Thialysine-resistant mutant of Salmonella typhimurium with a lesion in the thrA gene.

A mutant of Salmonella typhimurium was selected for its spontaneous resistance to the lysine analog, thialysine (S-2-aminoethyl cysteine). This strain, JB585, exhibits a number of pleiotropic properties including a partial growth requirement for threonine, resistance to thiaisoleucine and azaleucine, excretion of lysine and valine, and inhibition of growth by methionine. Genetic studies show that these properties are caused by a single mutation in the thrA gene which encodes the threonine-controlled aspartokinase-homoserine dehydrogenase activities. Enzyme assays demonstrated that the aspartokinase activity is unstable and the threonine-controlled homoserine dehydrogenase activity absent in extracts prepared from the mutant. These results explain the growth inhibition by methionine because the remaining homoserine dehydrogenase isoenzyme would be repressed by methionine, causing a limitation for threonine. The partial growth requirement for threonine during growth in glucose minimal medium may also, by producing an isoleucine limitation, cause derepression of the isoleucine-valine enzymes and provide an explanation for both the valine excretion, and azaleucine and thiaisoleucine resistance. The overproduction of lysine may confer the thialysine resistance.

Aspartate Kinase↗
PubMed1976

Core temperature in the female rat: effect of pinealectomy or altered lighting.

Radiotelemetry of core temperature in unrestrained, mature female rats revealed the existence of a 24-h rhythm that was bimodal. The principal peak occurred during the night under control conditions of 14 h light and 10 h darkness, and a less pronounced, secondary peak occurred 3-4 h after the onset of the light phase. Shifts in the phase of the photoperiod or alteration of the proportion of light per day revealed that the temperature rhythm was entrained by light, but that the two component peaks were governed by different aspects of the lighting regimen. Exposure of rats to continuous darkness, continuous light, or to a 20-h photoperiod revealed that the primary rhythm was endogenous, entrained by circadian photoperiods only, whereas the secondary rhythm was exogenous, requiring a circadian light/dark rhythm. A relationship between mean core temperature and ttion pressure, end-systolic L was constant, despite variations in filling and therefore independent of initial L and delta L; moreover, the L to which the ventricle shortened was determined by the course of the systolic force L-relation. Thus, irrespective of loading, delta L occurs within the confines of the contractile state-depdendent isovolumic force-L relation and where the latter is equivalent to the end-systolic force-length relation.

Animals↗
PubMed1976

Core temperature in the female rat: effect of ovariectomy and induction of pseudopregnancy.

Nocturnal peaks in core body temperature of rats during the estrous cycle were highest during the night of ovulation (2300-0200 h, proestrus-estrus) and lowest during the night before (diestrus 2-proestrus). Less dramatic diurnal secondary peaks, absent only during estrus, occurred 3-4 h after the onset of daylight. After induction of pseudopregnancy, mean temperature declined, but both daily peaks persisted until the first postluteal estrus, when the secondary peak was again absent transiently. Ovariectomy reduced mean core temperature and abolished all secondary peaks. In contrast, castration during pseudopregnancy did not abolish the secondary peaks. When cyclic rats were gonadectomized (abolishing the secondary rhythm) it was possible to re-establish this rhythm by stimulating the uterine cervix (as if to induce pseudopregnancy). However, in animals exposed to darkness (which also abolishes the secondary rhythm) reinduction by cervical stimulation was ineffective. These results indicated that the integrity of the secondary peak, though dependent on photoperiod, nevertheless was influenced by a neuroendocrine reflex arc.

Animals↗
PubMedDate not supplied

Effect of benomyl and carbendazim on steroid and molecular mechanisms in uterine decidual growth in rats.

The present study examined the influence of two benzimidazole fungicides benomyl and carbendazim (MCB), in dosages of 500 and 1000 mg kg-1 for 5 days, on the capacity of decidual growth in pseudopregnant rats. The aim of the research was to determine whether the antimitotic activity of both chemicals was being mediated by way of hormonal and molecular mechanisms at the uterine level. The results show that both fungicides produced reductions in uterine decidual weight (P < 0.01) and uterine protein content (P < 0.05). However, levels of serum estradiol and progesterone and the binding capacities of cytosol estrogen and progesterone receptors remained essentially unchanged. Subsequently, the antigrowth-antimitotic activity of benomyl and MCB, at 500 and 1000 mg kg-1 dosages, on the decidual uterus is direct, and apparently does not involve steroidal or receptor mechanisms.

Animals↗
PubMedDate not supplied

Hydroxyurea inhibition of cellular and developmental activities in the decidualized and pregnant uteri of rats.

The cytotoxicity of hydroxyurea (HU), currently used to combat various cancers, sickle cell anemia and human immunodeficiency infection, was assessed by exposing decidualized and pregnant uteri of Sprague-Dawley rats to this drug. Consecutive daily doses of HU (500 mg/kg(-1)) for 4 days were injected subcutaneously during decidualization when proliferation of the deciduoma was biochemically analyzed on pseudopregnancy day 9, or injected intraperitoneally during pregnancy when uterine developmental processes were evaluated on gestation day 16. Hydroxyurea displayed prominent antiproliferative effects on decidual growth. These actions were comparable to significantly impaired (P<0.001) developmental responses (increases in post-implantation losses, in resorbed fetuses and in reduced fetal and placental weights) during pregnancy. The cellular components inhibited by HU were DNA, protein, nitric oxide synthase, a matrix metalloproteinase and decidual prolactin-related protein mRNA (P<0.05). Steroid-related endocrine events (serum progesterone concentrations, estrogen receptor and mRNA levels) were unaffected by HU, implying direct cellular action by the drug. Interestingly, endometrial alkaline phosphatase bioactivity was enhanced by HU (P<0.05). Subsequently, the reproductive toxicity of HU was apparently related to mitogenic and differentiation-induced endometrial cellular activities.

Animals↗
PubMedDate not supplied

A mechanistic assessment of 1,3-butadiene diepoxide-induced inhibition of uterine deciduoma proliferation in pseudopregnant rats.

Butadiene diepoxide (BDE), a reactive metabolite of 1,3-butadiene that is an important industrial chemical used in synthetic rubber production causes a dose-dependent inhibition of deciduoma development in pseudopregnant Sprague-Dawley rats. This study used 4 daily i.p. BDE doses of 0.20, 0.25, 0.30, 0.35, or 0.40 to characterize mechanisms that may be responsible for the antideciduoma effect. Pseudopregnant rats were treated either before (pseudopregnancy [PPG] days 1-4) or after (PPG days 5-9) deciduoma induction by endometrial trauma with a blunt needle. Animals were killed on PPG day 9 and evaluated for serum progesterone and endometrial protein and DNA. RT-PCR was used to measure message for estrogen receptor (ER) alpha and pituitary adenylate cyclase-activating polypeptide (PACAP). Substrate zymography and Western blotting were used respectively to measure matrix metalloproteinase (MMP)-9 and inducible nitric oxide synthase. The antideciduoma effects of BDE were associated with decreases in endometrial weight, protein, and DNA, with decreases in serum progesterone, and with decreases in PACAP message and MMP-9. A reduction in NOS was identified at the highest dose of BDE. Message for estrogen receptor (ER) alpha was not affected at any dose. We conclude that the reduction in decidual proliferation was direct and appeared to be associated with either 1) a decrease in the effectiveness of the deciduogenic stimulation and/or a weakened endometrial sensitivity to the stimulus; or 2) an effect on deciduoma development. Molecular mechanisms that apparently contributed to BDE inhibition of decidual metabolism included the synthesis of protein and DNA involved in decidual growth, the synthesis and activation of a matrix metalloproteinase for degradation of the extracellular matrix that is essential for tissue remodeling during deciduoma development, and the nitric oxide/nitric oxide synthase and pituitary adenylate cyclase-activating peptide systems that are involved in promoting vasodilation and increased vascular permeability to enhance the availability of substrates for maximal deciduoma growth. The ovotoxicity of BDE, which has previously been established, may indirectly affect decidual proliferation by reducing progesterone, the preeminent endocrine regulator of deciduoma development. The findings also suggest that BDE may possess no estrogenic action since it was associated with endometrial weight loss and unaltered levels of the estrogen receptor alpha mRNA expression.

Animals↗
PubMedDate not supplied

Dexamethasone-induced changes in endometrial growth and inducible nitric oxide synthase during decidualization in rats.

1. The present study investigated the time-dependent inhibitory responses of endometrial growth and inducible nitric oxide synthase (iNOS) to dexamethasone during deciduoma development that was surgically induced on day 4 of pseudopregnancy (PG). 2. Groups of rats (n = 6) were subcutaneously injected with dexamethasone (1.5 mg/rat per day) for 3 days (PG days 1-3, 4-6, 7-9, 10-12 and 12-15). Rats in each group were killed on the last injection day. 3. Dexamethasone produced comparable temporal inhibitory changes in endometrial growth (wet weight, protein and DNA concentrations; P<0.0001) and in iNOS activity (130 kDa protein band), which peaked after PG days 4-6 and 7-9 pretreatments. 4. Endometrial matrix metalloproteinases (72 and 92 kDa) activity profiles displayed maximal reductions (36 and 53%, respectively) following PG days 4-6 pretreatment. Serum progesterone levels were equally (P<0.0001) but asynchronously inhibited by dexamethasone on PG days 9 and 12. 5. Dexamethasone inhibition of endometrial growth and in situ iNOS was most pronounced during decidual development (PG days 4-9). Minor reductions in these endometrial parameters occurred before deciduoma induction (PG days 1-3) and during deciduoma regression (PG days 10-15). 6. These results indicate that, in the endometrium, the iNOS/endogenous nitric oxide system may be linked to the biochemical and metabolic mechanisms responsible for the developmental responsiveness of the deciduoma to dexamethasone exposure. These time-dependent changes in endometrial growth and iNOS apparently were not mediated by progesterone.

Animals↗