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PubMed1996

Morphology of ricin and abrin exposed endothelial cells is consistent with apoptotic cell death.

Cultures of bovine pulmonary endothelial (BPE) cells were exposed to LC70 doses of ricin or abrin (15.5 and 4.5 pM respectively) over a period of up to 40 h. The viability of the cultures (as determined by the neutral red (NR) dye retention assay) declined after 6 h exposure to the toxins. From 15 h onwards, cellular material in toxin exposed cultures became detached from the substratum of the culture vessels. Hoffman modulation contrast photomicrography showed that this process was due to ricin and abrin exposed cells collapsing into membrane bound vesicles which retained the NR dye, became detached and floated into the medium. These apoptotic-like structural changes were further investigated by transmission electron microscopy (TEM) and by agarose gel electrophoresis of DNA from control and exposed cultures. Many of the characteristic changes associated with apoptotic cell death were seen using TEM, including heterochromatin condensation at the nuclear periphery, crenulation of the nuclear membrane and progressive degeneration of residual nuclear and cytoplasmic structures. The plasma membrane of many cells remained intact, and contained nuclear and cytoplasmic debris. Agarose gel electrophoresis of DNA extracted from toxin-treated cells revealed oligonucleosome sized DNA fragments, characteristic of apoptosis, from adherent cells at 7 h and both adherent and floating populations when harvested from 15 h; DNA from unexposed control cells did not show this fragmentation. The identification of apoptosis as being a significant additional mechanism of toxicity following exposure to ricin and abrin holotoxins raises the possibility of developing new therapeutic strategies against poisoning by these phytotoxins.

Abrin↗
PubMed1996

Feedback actions of estradiol on GnRH secretion during the follicular phase of the estrous cycle.

The pattern of GnRH secretion during the follicular phase of the estrous cycle of sheep is characterized by an initial marked change in episodic secretion (increased frequency and decreased amplitude) followed by a massive and sustained discharge-the preovulatory GnRH surge. Studies employing a physiological model for the follicular phase have revealed that estradiol has profound and complex feedback effects on GnRH release during the preovulatory period. These include both quantitative effects on pulses (stimulation of frequency, inhibition of amplitude) and qualitative effects (altering pulse shape, stimulating interpulse secretion), in addition to inducing a preovulatory GnRH surge. In stimulating the surge, estradiol causes a highly characteristic change in the minute-to-minute pattern of GnRH in hypophyseal portal blood. Initially, a strictly episodic pattern gives way to one in which GnRH is consistently elevated between pulses. Then, following enhancement of both pulsatile and interpulse components, GnRh becomes extremely high and variable for the majority of the surge. From this point, a regular and well organized pulse pattern is not apparent. The characteristic time course of GnRH at surge onset provides insight into possible mechanistic changes in the GnRH neurosecretory system. Such changes include quantitative and qualitative alterations in the pulse generating mechanism, recruitment of a surge specific population of GnRH neurones, morphologic alterations in GnRH neurones and neighboring cells, and changes in efficiency or route of delivery of GnRH from its site of release to the portal vasculature. These possibilities, while untested and speculative, provide a conceptual framework for future research.

Animals↗
PubMed1975

Cell electrophoretic studies on the cellular immune response to Candida albicans in rabbits.

Rabbits were sensitized intracutaneously with Candida albicans total antigen by a series of booster injections. The electrophoretic migration time of lymph node lymphocytes was related to the time after injection. Two lymphocyte sub-populations could be distinguished. The proportion of each, changed during the course of the immune response. Characteristic changes also took place after in vitro incubation with Candidin. The results have been compared with agglutination titers and are discussed in relation to bursa and thymus-derived cells. The electrophoretic method may be valuable for the diagnosis of candidiasis.

Animals↗
PubMed1995

Two decades of family change: secondary analysis of continuous government surveys.

"Secondary analysis of General Household Survey and Labour Force Survey data shows how the structure of families in Great Britain has changed over the last 20 years. Dependent children are now less likely to be living in a couple family and more likely to be living with a lone mother who is either single or divorced. Families in simple households with just two generations have become more common over time. Lone mothers are now more likely to be living in simple households. The paper also considers how the number and ages of dependent children are associated with family and household type. Log-linear models are used both to smooth the data and to predict family structure in the year 2000. Gaps in our knowledge about current family structures are discussed together with implications of the findings for social policy."

Adolescent↗
PubMed1994

[[Demographic foundations of elderly living arrangements: a simulation study of intergenerational coresidence]].

"In this paper we employ family status life tables to assess the effects of demographic processes on family composition and to reveal trends in elderly living arrangements [in Taiwan]. We found that further declining fertility and changing nuptiality are responsible for the prevalence of nuclear family composition. [The] increasing proportion of nuclear families indicates a decreasing probability [of] elderly parents living with their married children. In addition, according to the current nuptiality trends, the increasing proportion of women of all ages who remain [unmarried] will strengthen its effects on family composition in the near future." (SUMMARY IN ENG)

Adult↗
PubMedDate not supplied

Abandoning the retentionist model: family and marriage change among the East Indians in rural Trinidad.

East Indian family life in rural Trinidad is usually analyzed within the framework of the retentionist model, which holds that the East Indians have successfully retained the basic institutions of their home culture. A restudy of Felicity village demonstrates that the model underestimates the impact of social and economic developments on family and marriage life in this community because it focuses mainly on ideal patterns of culture.

Culture↗
PubMed1986

An experimental analysis of the origins of somatostatin-like immunoreactivity in the dentate gyrus of the rat.

In previous studies, fibers demonstrating somatostatin-like immunoreactivity were observed in the outer half of the molecular layer of the dentate gyrus in the rat and monkey. They occupy the same region as those of the perforant pathway that originates in the entorhinal cortex. Numerous somatostatin immunoreactive neuronal cell bodies were also observed in the hilar region, though stained axonal profiles could not be followed from these cells into the molecular layer. In the present study, several experimental procedures were employed to determine the origin of the somatostatin-positive fibers in the molecular layer. Transection of the perforant path fibers resulted in such characteristic changes as shrinkage of the molecular layer and sprouting of AChE-positive fibers. There was no apparent decrease, however, in the density of somatostatin-positive fibers. In fact, since the stained fibers occupied a narrower band in the shrunken molecular layer, their density appeared greater. Injections of kainic acid into the hilar region produced a lesion of hilar neurons, including those positive for somatostatin. In the region of cell loss, there was a marked reduction of somatostatin-immunoreactive fibers in the ipsilateral molecular layer, with no detectable changes in the homotopic contralateral molecular layer. The distribution of AChE fibers, which presumably have an extrinsic origin, was not altered by the treatment. In a final series of experiments, the retrograde tracer wheat germ agglutinin-horseradish peroxidase (WGA-HRP) was injected into the hilar region and sections were prepared for the simultaneous demonstration of the tracer and of somatostatin-like immunoreactivity. Somatostatin-positive neurons demonstrating WGA-HRP reaction product were observed primarily in the ipsilateral hilar region, but a few double-labeled cells were also seen in the same area of the contralateral side. These studies indicate that a population of intrinsic neurons located in the polymorphic layer of the dentate gyrus projects to the outer half of the ipsilateral molecular layer. A similar, but very much smaller, projection also extends to the contralateral dentate gyrus. Taken together, these projections appear to account for much of the somatostatin-like immunoreactivity in the molecular layer of the dentate gyrus.

Animals↗
PubMed1988

Age related changes in the human plastron: a roentgenographic and morphologic study.

Characteristic changes that can be demonstrated on roentgenograms occur with increasing age in the plastron (chest plate) of humans. These alterations include progressive ossification in the costal cartilages (located characteristically in the sternal rib end, centrichondrally, and peristernally--often with sex and age distinctive patterns), maturation of the newly formed bone with trabeculation formation, loss of the smooth contour of the costo-manubrial junction, cupping of rib ends, osteoporotic changes, and arthritic changes in the sternal head of the clavicles. The sequence of development of these alterations has been examined by X-ray of 1965 cadavers of 15 years of age or over and correlated with the gross bone and cartilage morphology changes in many cases. This technique allows for age determination within 5 years of real age in 55% of cadavers and within 25% of real age in 95% of all cadavers. The greatest departures from real age are in the over-60-year groups. The same roentgenograms can allow for correct sex prediction in 99% of the population.

Adolescent↗
PubMed1985

Differential sensitivity of human breast cancer cell lines to the growth-inhibitory effects of tamoxifen.

In eight estrogen receptor (ER)-positive breast cancer cell lines (including three sublines of MCF-7) and five ER-negative breast lines, the action of the nonsteroidal antiestrogen, tamoxifen, was studied, and the concentrations of ER and antiestrogen binding site were measured. The concentration of antiestrogen binding site was significantly [P less than 0.005] greater in ER-positive cells [236,600 +/- 29,900 (SE) sites/cell] than in ER-negative cell lines [66,600 +/- 16,800 sites/cell]. In ER-positive cell lines, a cell cycle phase-specific growth-inhibitory effect, 20% inhibitory dose less than 0.1 to 1.0 microM, was seen which was shown for some representative cell lines to be estrogen reversible. Within this group of cell lines, the degree of tamoxifen-induced inhibition of growth correlated with control population doubling time, but not ER or antiestrogen binding site concentration. The changes in cell cycle kinetic parameters characteristic of all ER-positive lines were a decrease in percentage of S-phase cells and a corresponding increase in percentage of G0-G1 cells. In all cell lines, 5 to 12.5 microM tamoxifen caused cytotoxicity, and this was shown to be estrogen-irreversible in 3 representative cell lines; moreover, estradiol synergistically enhanced the cytotoxic effects of tamoxifen under some experimental conditions. The cell cycle effects of tamoxifen in three ER-negative cell lines (Hs0578T, MDA-MB-231, MDA-MB-330) were decreased proportions of G0-G1 cells with an increase in percentages of S and G2+M cells. These results implied that the mechanism of tamoxifen cytotoxicity may differ in ER-positive and ER-negative breast cancer cells. However, although the ER-negative BT-20 line was much less sensitive to tamoxifen than were the ER-positive cells, growth inhibition and cytotoxicity in this line were associated with a slight decrease in percentage of S-phase cells. These results confirm that ER-positive breast cancer cells are more sensitive (4- to greater than 75-fold) than ER-negative breast cells to the growth-inhibitory effects of tamoxifen and demonstrate that, in all ER-positive cells, growth inhibition and cytotoxicity are accompanied by characteristic changes in cell cycle kinetic parameters. In contrast, different mechanisms may be involved in the effects of tamoxifen on different ER-negative cell lines.

Breast Neoplasms↗
PubMed1985

[Effect of hypobaric hypoxia on motor behavior in rats].

Hypobaric hypoxic exposure for 18 h (pO2 8.7 kPa) effects characteristic changes of motoric behaviour in adult rats. We observed a posthypoxic increase of spontaneous locomotion and of open-field activity. 24 h after hypoxic exposure the locomotion stimulated by dopaminergic agonists apomorphine or amphetamine was strengthened. Dopaminergic nuclei showed a different sensitivity to unilaterally applied dopamine after hypoxic exposure. Rotational behaviour was facilitated in the nucleus accumbens but significantly decreased in the substantia nigra. In the nucleus caudatoputamen we could not prove changes in comparison to controls. These results indicate that central dopaminergic processes are influenced by hypobaric hypoxic exposure. Besides the sensitization of dopaminergic receptor populations these changes of motoric behaviour may be connected with interactions between different transmitter systems or displacement of central regulation systems.

Amphetamine↗
PubMed1994

[Comparison of four different methods for respiratory determination of the anaerobic threshold in normal people, and heart- and lung patients].

We analyzed 128 cardiopulmonary exercise tests (CPX), performed in normal subjects (n = 31), in patients with coronary artery disease (n = 41), with chronic heart failure before (n = 14) and after (n = 14) application of oral PDE-inhibitors and in patients with HIV-infection on a bicycle-ergometer in semi-supine position using a ramp-program (dependent on study-population with 15, 20 or 35 Watt/min increases) with respect to the ability to determine the respiratory anaerobic threshold non-invasively, using the main criteria described by Wasserman et al.: the V-slope-method according to Beaver, the increase of the ventilatory equivalent for O2 (VE/VO2), the increase of the end-tidal PO2 (PETO2) and the increase of the respiratory quotient (RQ) during exercise. In the different study-populations we calculated the detection rates of the AT for each criteria separately. The typical changes in the end-tidal PO2 (124/128 = 96.9%) and the V-slope-method (119/128 = 92.9%) were the most reliable parameters to detect the anaerobic threshold. The characteristic changes of the ventilatory equivalent for O2 (VE/VO2) and of the respiratory quotient (RQ) we found in 100/128 (= 78.1%) and in 107/128 (= 83.6%) of the tests respectively. 86/128 tests (67.2%) showed typical changes in all four mentioned criteria. In another 24/128 tests (19.8%) three of four criteria were fulfilled. Therefore, our investigations showed that in 110/128 cases (85.9%) the AT could be determined by typical changes by means of at least three of the four described parameters. In 15/128 (11.7%) tests only two of four criteria were fulfilled.(ABSTRACT TRUNCATED AT 250 WORDS)

Anaerobic Threshold↗
PubMed1993

Multivesicular bodies in HEp-2 cells are maturing endosomes.

Conventional fluorescence microscopy of fixed HEp-2 cells as well as video microscopy of living cells incubated with transferrin-Texas Red (Tf-TxR) for < 60 min revealed distinct punctuate endosomal structures. Quantitative ultrastructural analysis using horseradish peroxidase (HRP) and cationized gold as tracers showed that spherical multivesicular bodies (MVBs) were the predominant endocytic compartments in HEp-2 cells and that MVBs within 60 to 90 min matured into lysosomes still containing internal vesicles. The number of labeled MVBs increased continuously from 2.5 min to 30 min of tracer incubation. However, when the cells were pulsed for 5 min followed by 10 or 25 min chases, the number of labeled MVBs corresponded to that obtained after 5 min of continuous incubation. The diameter of labeled MVBs was largely constant with time, but the number of internal MVB vesicles increased. Thus, early or newly formed MVBs contained few internal vesicles, whereas late MVBs, that is to say, MVBs that have existed for some period of time, contained numerous internal vesicles, and finally a mixture of membranous material or myelin figures and vesicles. It is thus in principle possible to distinguish between early and late MVBs in HEp-2 cells on the basis of morphology. However, the difference in number of internal vesicles applies only to the entire MVB population; after only 2.5 to 5 min of incubation, MVBs with numerous internal vesicles could also be reached by internalized tracer. Concomitant with the gradual changes in morphology, the MVBs also showed a characteristic change in content of marker proteins as detected by immunogold labeling on ultracryosections. Hence, early MVBs with relatively few internal vesicles and typically reached by internalized tracers within 5 min contained transferrin receptors (TfRs). By contrast, MVBs with many internal vesicles and labeled after 60 min of incubation contained mannose-phosphate receptors (MPRs), and the MVBs with distinct membranous material or myelin figures in addition to the internal vesicles were enriched in the lysosome membrane protein lamp-1. Thus, there seems to be a gradual maturation of MVBs in HEp-2 cells.

Carcinoma, Squamous Cell↗