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Biomedical subjects

A Altman

Publications and source records attributed to A Altman.

At least 181 records · Page 10Linked to original sources

The biologic effects of allogeneic effect factor on T lymphocytes. I. The mitogenic activity and the autonomous induction of cytotoxic T lymphocytes by AEF.

Studies presented herein illustrate the capacity of the soluble mediator, allogeneic effect factor (AEF), which is derived from histoincompatible cell interactions, to induce the in vitro differentiation of normal murine splenic lymphocytes into mature cytotoxic cells capable of exerting activity on H-2-identical target cells. This process requires the presence of T lymphocytes during the sensitization phase, and the lytic activity on tumor cells is mediated by cytotoxic T lymphocytes (CTL). The capacity of AEF to induce differentiation of such CTL does not require the presence of stimulating target cells in the sensitization phase. The induction of CTL requires the presence of AEF at the initiation of culture, although exposure to AEF as brief as 1 hr is sufficient to induce fresh spleen cells to differentiate into CTL during the subsequent 5 days in culture. In addition to its ability to induce CTL, AEF is highly mitogenic for T lymphocytes. However, the mitogenic and the CTL-inducing activities of AEF can be experimentally dissociated, indicating that different subpopulations of T lymphocytes may be involved in the response to AEF. In contrast to similar soluble helper factors derived from allogeneic cell interactions, AEF appears to be unique in its ability to autonomously induce a primary CTL response in vitro.

Animals↗

Direct cloning of human neuroblastoma cells in soft agar culture.

An in vitro soft agar technique was used in an attempt to culture neuroblastoma cells from 71 bone marrow, 3 lymph node, and 2 solid tumor specimens from 18 patients with neuroblastoma. One-half of each specimen was sent for routine pathology studies and one-half was cultured in the soft agar system. Colonies appeared within 10 days in histologically positive bone marrows. Light microscopy, electron microscopy, catecholamine secretion, and karyology provided evidence that the colonies were composed of neuroblastoma cells. There were 38 instances in which histological study of the specimen demonstrated neuroblastoma cells. The soft agar system showed colony growth in 30 of these samples (79%). There were a total of 38 specimens that were histologically negative for neuroblastoma. Thirty of these 38 specimens showed no growth in the stem cell assay. Eight histologically negative specimens from 6 patients formed colonies in the soft agar system. Five of these 6 patients showed tumor histologically on prior or subsequent marrow examinations. In addition to a significant correlation between histological and soft agar culture results (p < 0.001), there exists a highly significant positive correlation between the number of colonies per plate and the histological status of the specimen (p < 0.005). Serial marrow samples were cultured on 7 patients. There appears to be an association between the number of colonies that develop in the plate and the clinical course and prognosis of the patient. Decreasing plating efficiencies (number of colonies per number of cells plated) correlated with tumor response. Increasing plating efficiencies indicated tumor relapse. A plating efficiency of greater than or equal to 0.1% portended a particularly poor prognosis. Neuroblastoma grows well in this soft agar culture system. This excellent growth provides a good model for both clinical and basic science studies of neuroblastoma.

Abdominal Neoplasms↗

Biological effects of allogeneic effect factor on T lymphocytes: in vitro induction of cytotoxic T lymphocytes manifesting preferential lytic activity against H-2-identical tumor cells.

The studies reported herein were designed to determine the effects of allogeneic effect factor (AEF), a soluble mediator generated in the course of allogeneic cell interactions, on the differentiation of cytotoxic T lymphocytes in vitro. Normal, unprimed spleen cells from various strains of mice cultured with AEF for 5 days, in the absence of any stimulator cells, developed into cytotoxic lymphocytes capable of lysing target cells in a short-term 51Cr release assay. T lymphocyte-depleted spleen cells did not become cytotoxic when cultured with AEF, and the cytotoxic cells themselves were found to be T lymphocytes. AEF-induced cytotoxic T lymphocytes preferentially lysed H-2-identical target cells. Thus, AEF, as opposed to similar "helper" factors derived from mixed lymphocyte cultures, appears to be unique in its ability to trigger normal, unprimed T lymphocytes to differentiate into cytotoxic T lymphocytes in the absence of specific antigenic stimulation.

Animals↗

Role of Ethylene in Abscisic Acid-induced Callus Formation in Citrus Bud Cultures.

The induction of callus formation in cultured buds of Shamouti orange (Citrus sinensis [L.] Osbeck) by abscisic acid (ABA) is a multiphasic process. (Altman, and Goren 1974 Physiol Plant 32: 55.) A study of the mediation by ethylene on this effect of ABA was undertaken. It was found that: (a) ethylene and (2-chloroethyl) phosphonic acid, as well as ABA, induced callus formation; (b) callus induction is best attained when explants are exposed to ethylene during the 1st day after excision; and (c) ABA-induced callus formation is inhibited by rhizobitoxine analog, an inhibitor of ethylene biosynthesis. It is concluded that the effect of ABA on callus formation is mediated via ethylene.

Journal Article↗

Cytotoxic activity of guinea-pig lymph node cells stimulated in vitro.

Guinea-pig lymph-node cells (LNC) cultured for 5 days in medium containing fetal calf serum (FCS) were cytotoxic to various target cells. LNC cultured in medium supplemented with fresh, autologous guinea-pig serum (GPS) instead of FCS were not detectably cytotoxic unless agents that stimulate lymphocyte proliferation were added to the culture medium. The stimulating agents we studied were 2-mercaptoethanol (2-ME), syngeneic tumor cells, allogeneic peritoneal exudate cells (PEC) and the T-cell mitogens concanavalin A (Con A) and phytohemagglutinin (PHA). LNC cultured in the presence of these agents were cytotoxic to normal syngeneic fibroblasts and to syngeneic, allogeneic or xenogeneic tumor cells but not to PHA-induced lymphoblasts. Potentiation of cytotoxicity in vitro was accompanied by a marked proliferation of the cultured LNC; the combination of several stimulatory agents had an additive effect on the generation of cytotoxicity in culture.

Animals↗

Simultaneous performance on verbal, nonverbal and motor tasks by right-handed adults.

A series of four dual task experiments was conducted in which different groups of right-handed Ss (N1 = 24; N2 = N3 = N4 = 18) simultaneously performed a repetitive finger tapping task in conjunction with: (a) a verbal fluency task (Experiment I); (b) listening to logical memory stories from the Weschler Memory Scale (Experiment II); (c) reading logical memory stories (Experiment III); and (d) scanning an array of faces (Experiment IV). Results indicated that all three verbal tasks produced significant asymmetrical depression in tapping performance, with the right hand being more disrupted then the left. The visuo-spatial task, however, exerted symmetrical bilateral depression of both hands. Performance on the cognitive tasks (number of words produced in the verbal fluency task; recall of stories either listened to or read, recognition of faces) was unaffected by simultaneous digital tapping.

Adult↗

Dual Mechanisms in Polyamine-mediated Control of Ribonuclease Activity in Oat Leaf Protoplasts.

Dibasic amino acids and polyamines added to oat (Avena sativa L.) leaf protoplast isolation media decrease the RNase activity of extracted protoplasts relative to controls. This effect, which is manifested even when the added polyamine is removed by exhaustive dialysis prior to assay, is due to a prevention of the rise in RNase activity which usually follows protoplast isolation. Polyamines, but not dibasic amino acids, also decrease RNase activity in vitro. This in vitro effect seems to result from electrovalent attachment of the polyamine to the RNA, because the greater the net positive charge on the polyamine, the greater is its inhibitory effect in vitro. The activity of dibasic amino acids when added during protoplast isolation probably results from their conversion to polyamines.

Journal Article↗

Differential effects of sucrose, abscisic Acid, and benzyladenine on shoot growth and callus formation in the abscission zone of excised citrus buds.

The omission of sucrose from the basal medium stimulated callus formation in bud explants of Citrus sinensis (L.) Osbeck. Moreover, it increased the abscisic acid-induced callus proliferation reported earlier in the presence of 5% sucrose (Altman and Goren, Physiol. Plant. 32: 55, 1974). The inhibition of callus formation by the addition of sucrose was not due to the high osmotic potential of the medium. Benzyladenine induced callus formation slightly, in all sucrose concentrations up to 5%. The high level of sucrose was required, however, for the growth of shoots from buds cultured on both basal and benzyladenine-containing media.The uptake of (14)C-sucrose by bud explants was linear for at least 98 hr, and was enhanced significantly by both abscisic acid and benzyladenine during the initial 24-hour period. Abscisic acid enhanced the absorption of (14)C-sucrose and the accumulation of sugars in buds cultured at high levels of sucrose. More than 50% of the total label accumulated in the callus of abscisic acid-treated explants whereas only 16 and 23% were observed in the growing shoots of control and cytokinin-treated explants, respectively.Results suggested that while sucrose "starvation" induced initial callus formation, high levels retarded further proliferation of the callus.

Journal Article↗

Stabilization of Oat Leaf Protoplasts through Polyamine-mediated Inhibition of Senescence.

Protoplasts isolated from Avena sativa L. leaves undergo progressive senescence when incubated aseptically in 0.6 m mannitol with or without added nutrients. This senescence is manifested by morphological deterioration and ultimate lysis of protoplasts, by a decrease in incorporation of [(3)H]uridine and [(3)H]leucine into macromolecules, and by a sharp increase in ribonuclease activity.The presence in the incubation medium of l-arginine, l-lysine, certain polyamines related to these amino acids (cadaverine, putrescine, spermidine), Ca(2+), or streptomycin stabilizes the protoplasts. Protoplasts incubated with 10 mml-arginine or l-lysine show an initial inhibition of [(3)H]uridine incorporation, but with time, incorporation is restored to levels greater than in control protoplasts. The rise in ribonuclease activity of protoplasts is completely inhibited if the protoplasts are incubated with 10 mml-arginine. Greater incorporation of [(3)H]uridine into RNA of aging protoplasts is also maintained by appropriate concentration of cadaverine, putrescine, spermidine, Ca(2+), or streptomycin in the incubation medium; the same concentrations of these substances stabilize the protoplasts against additional lysis.

Journal Article↗

Cell-free media of mixed lymphocyte cultures augmenting sensitization in vitro of mouse T lymphocytes against allogeneic fibroblasts.

Using an in vitro mouse lymphocyte anti-fibroblast reaction (AFR), we recently reported that the addition of allogeneic stimulator lymphocytes to the sensitization phase of the AFR enhanced sensitization to fibroblast antigens as evidenced by a marked increase in the cytolytic activity of the sensitized lymphocyte population. In the present report we studied the mechanism of this helper effect by testing the capacity of cell-free media derived from 48-h mixed spleen cultures to enhance anti-fibroblast sensitization. We found that such cell-free media could produce a marked helper effect when applied to the sensitization phase of the AFR, but not when added to the cytolytic effector phase. The stimulator cells in the mixed lymphocyte culture (MLC) did not have to be syngeneic with the sensitizing fibroblasts in the AFR in order for the helper effect to be demonstrated. Lymphocytes sensitized to fibroblast antigens in the presence of MLC medium retained their specificity of the effector phase. Our data suggest that the MLC medium acts by enhancing differentiation processes of antigen-triggered lymphocytes. Generation of helper activity by the MLC was abolished by 1000 r irradiation of the responder cells. By using nu/nu and normal spleens, both from two different strains, as cell sources for the MLC, we found that the generation of helper activity depended on T cells capable of proliferation. Furthermore, stimulator lymphocytes differing from responder lymphocytes by non-H-2 alloantigens as well as by point mutation with the H-2 complex were capable of eliciting helper factor(s). Thus, soluble factor(s) produced in a MLC, which are dependent on T lymphocyte proliferation, have the capacity to enhance the sensitization of mouse lymphocytes against antigens present on allogeneic fibroblasts.

Animals↗

Augmentation of cell mediated lysis (CML) by THF.

The in-vitro model of cell mediated lysis (CML) was used to study whether a thymic hormone (THF) participates in the processes which lead to generation of effector cells. It was found that THF increases the capacity of effector cells from spleens of intact mice in the CML assay. This effect of THF on generation of effector cells was manifested when THF was present during the mixed lymphocyte culture. On the other hand, addition of THF to the effector (CML) phase did not elevate the lytic capacity of killer cells. Moreover, THF compensated the impaired lytic capacity of effector cells from adult thymectomized mice and raised it to the level of intact mice. The results are compatible with the hypothesis that THF acts on the generation of CML effector cells of both intact and adult thymectomized mice.

Animals↗

Heterogeneity in the development of cytotoxic T lymphocytes in vitro revealed by sensitivity to hydrocortisone.

In the present study we used hydrocortisone (HC) treatment in vivo as a probe to analyze two different in vitro systems for the regeneration of cytotoxic T lymphocyte (CTL), namely the antifibroblast reaction (AFR) and the mixed lymphocyte culture (MLC) system. We found that cells remaining in the thymus after HC treatment had increased reactivity in these two systems. However, the same treatment in the spleen severely depressed the MLC reactivity in both the proliferative and the cytolytic phases, while markedly increasing the AFR reactivity. These findings demonstrate heterogeneity of CTL precursors and/or their pathways of differentiation into effector cells. In addition, MLC-reactive cells in the thymus appear to be distinct from such cells in the spleen, as judged from their differential sensitivity to HC.

Animals↗

Human figure drawings in a prospective study of six disorders: hypertension, coronary heart disease, malignant tumor, suicide, mental illness, and emotional disturbance.

To test the hypothesis that human figures drawn by young adults are potential predictors of future disease states, drawings of 204 former medical students were examined 13 to 23 years later. During the interval, the 102 subjects in the experimental group developed one of six specified disorders, while the 102 subjects in the control groups remained in good health. Drawings were classified in eight categories based primarily on the stance of the figure. Categories of drawings found to be distinctive for the various groups are: healthy control groups: the neutral or uncommitted attitude; hypertension/coronary group: the inviting or input-demanding attitude; malignant tumor group: the attitude of ambivalence or conflict; suicide/mental illness group: the self-related or withdrawal attitude; emotional disturbance group: incomplete figures, bizarre figures, action scenes. Thus the evidence suggests that the stance of the figure drawing reflects the subject's attitude toward the outside world. When the category profiles of groups are compared, the following differences are found at levels of statistical significance: the total experimental group is different from the total control group; the somatic subset, "Body Takes the Rap" is different from the psychological subset, "Psyche Takes the Rap"; and the hypertension/coronary group, malignant tumor group, and emotional disturbance group are different from their specific control groups. It is concluded that human figure drawings by this population have predictive potential for certain future disease states, and that there are psychological precursors of somatic disease.

Coronary Disease↗