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N Hollander

Publications and source records attributed to N Hollander.

49 records · Page 3Linked to original sources

The effect of cytochalasin B on effector--target cell interaction. Quantitative and ultrastructural study.

Interaction between pokeweed mitogen-stimulated secondary lymphocytes (PWM-lymphocytes) and target fibroblasts resulted in over 80 per cent adherence of the sensitized lymphocytes to the target cells. Adherence is by pseudopod penetration into target fibroblasts. The only lymphocyte cellular components found in the contact region were microfilaments. Cytochalasin B completely inhibited the specific adsorption of the PWM-secondary lymphocytes to the target cells. What adhesion did take place in the presence of cytochalasin B was found to be nonspecific. Ultrastructurally, the contact between lymphocyte and target cells was altered by the drug, when pseudopods were not observed. Possible effects of cytochalasin B on lymphocyte-mediated cytolysis, mainly by its effect on microfilament function, is discussed.

Animals↗

In vitro generation of memory lymphocytes reactive to transplantation antigens.

The in vitro generation of memory cells reactive to transplantation antigens is described. Blast cells, obtained from rat lymphocytes sensitized on xenogeneic or allogeneic fibroblast monolayers, reverted to secondary small lymphocytes after transfer from the foreign sensitizing to syngeneic monolayers. These secondary small lymphocytes had a limited in vitro life span of 4-6 wk. They manifested properties of memory cells: upon re-exposure to fibroblasts of the sensitizing phenotype, the secondary lymphocytes adhered to the fibroblast monolayer and transformed into blast cells with cytotoxic activity. The response of secondary lymphocytes was rapid, compared to that of normal lymphocytes, and directed specifically against the primary sensitizing antigens.

Animals↗

Specific adherence of in vitro differentiated lymphocytes to target cells.

Blast cells which were derived from rat lymphocytes by stimulation with phytohemagglutinin (PHA), concanavalin A (Con A), or pokeweed mitogen (PWM) transformed within 2-3 days into a new type of lymphocytes when plated without mitogen on embryo fibroblast monolayers. These lymphocytes were termed secondary lyrophocytes. Upon addition of PWM to PWM-secondary lymphocytes a marked adherence to fibroblast monolayers was observed. The degree of adherence was estimated (a) by direct count of the lymphocytes in the medium and in the trypsinized fibroblast fraction, and (b) by using (51)Cr-labeled lymphocytes. The adherence process required incubation at 37 degrees C. The process started immediately after the addition of PWM and reached a plateau at 6 hr. At this time more than 80% of the lymphocytes adhered. In the absence of PWM only 12% of the lymphocytes were found in the fibroblast fraction. Unlike PWM-lymphocytes. Con A-lymphocytes, PHA-lymphocytes, and ordinary lymphocytes taken directly from the rat lymph nodes adhered only slightly more in the presence of PWM (10-20% adherence of ordinary lymphocytes) than in its absence (8% adherence). The adherence of the secondary lymphocytes and the ordinary lymphocytes was also studied in the presence of Con A and PHA. These mitogens induced high rate of adherence and they did not demonstrate specificity in their action. The adherence was accompanied by transformation of the lymphocytes to blast cells endowed with target-cell lytic ability. This transformation occurred mostly in the adhering fraction of the lymphocyte population. The results support the notion that target-cell recognition and destruction in cellular immunity involve contact between the cells.

Animals↗

The development of hypersensitive lymphocytes in cell culture.

An in vitro cell-mediated immune response to pokeweed mitogen (PWM) is described. Rat lymphocytes were stimulated by PWM, by phytohemagglutinin (PHA), and by concanavalin A (ConA). In the presence of PWM only a fraction of the lymphocytes underwent blastogenesis. This was in contrast to the apparent total blastogenesis obtained in response to PHA or ConA. When blast cells derived from each of the mitogens were plated on rat fibroblast monolayer in the absence of mitogen they differentiated into a distinct type of lymphocyte termed "secondary lymphocyte." Addition of mitogens to cultures of these lymphocytes resulted in a retransformation to blast cells. The secondary lymphocytes were tested for their ability to effect lysis in the presence of each of the three mitogens. In. the presence of PWM, lysis of fibroblasts produced by PWM-lymphocytes was considerably more efficient than lysis obtained by ConA- or PHA-lymphocytes. No difference in effect on target fibroblasts was obtained when the three types of secondary lymphocytes were tested in the presence of either PHA or ConA. The stimulating action of PWM on lymphocytes was shown to be immunologically specific. No such specificity was found in the case of PHA or ConA. The results are interpreted to indicate that PWM combines with cell membranes and acts on the lymphocytes as a "transplantation antigen." Lymphocytes capable of responding to "PWM-transplantation antigen" transform to blast cells capable of specifically lysing PWM-conjugated fibroblasts. In the absence of the mitogen, PWM-induced blast cells differentiate to lymphocytes hypersensitive to PWM.

Animals↗

Homicides of abused children prematurely returned home.

Five homicides of abused children are reviewed. These children had been removed from the parents because of physical abuse, then later returned to the home where they were subsequently killed. In each case, certain factors were present either during the interval of removal or after the return of the child, which could have alerted individuals, agencies or the court and, if heeded, could have prevented the deaths. Premature return occurred because of administrative inadequacies, including abbreviated investigations, violation of routine procedures because of heavy caseloads, and inadequate or absent psychotherapy of parents or caretakers. Court dates are not extended to compensate for these failings. The factors which operate in the home after the return of the child are essentially the same as those which prompted the removal: physical abuse. In these circumstances, more frequent follow-up visits by the agency or social worker are necessary and for a longer period of time. There should be a heightened awareness that in children who are returned home after removal for physical abuse, further physical abuse is a signal for immediate removal before a fatality occurs.

Child Abuse↗

Beta-endorphin in the brainstem, pituitary, and spinal fluid of infants at autopsy: relation to sudden infant death syndrome.

Immunohistochemical localization of beta-endorphin was studied in the pituitaries and medullas of forty human infants at autopsy. beta-Endorphin immunoreactivity was found in anterior pituitary cells in all cases. In the medulla, beta-endorphin immunoreactivity was found in the neurons of the medial and lateral cuneate nuclei in ten out of the forty cases. In eight of these ten cases, the infants died of causes other than sudden infant death syndrome (SIDS). Only two of 25 SIDS cases had demonstrable beta-endorphin in the brainstem nuclei. Beta-endorphin levels in the spinal fluids of all the cases showed no correlation to cause of death, age or gender.

Brain Stem↗

Lysis and necrosis: analysis of two cytotoxic phenomena mediated by lymphocytes.

Stimulation of rat lymphocytes by allogeneic and xenogeneic (mouse) embryo fibroblast monolayers or by pokeweed mitogen (PWM) generate two different cytotoxic manifestations: a) cell-mediated target cell lysis obtained by contact between effector cells and target cells; b) cytotoxicity caused by lymphotoxin (here termed "necrosis"). Activation of hypersensitive lymphocytes by soluble antigen, e.g., keyhole limpet hemocyanin (KLH), produces only necrosis but no lytic effect. This difference between mitogen and antigen activation is attributed to the affinity of the mitogens for target cell membranes. There is a marked difference in the time of onset of the two phenomena. Ten minutes after the effector cells have been introduced to the target monolayers, lysis of fibroblasts becomes visible, whereas necrosis usually develops only 48 to 72 h later. A clear difference in the morphology of the two types of target cell killing was seen when the cultures were stained in situ with trypan blue. Lysed target cells produced blebs and underwent fragmentation, scattering cytoplasmic droplets. During a 10-min to 24-h period, these cells excluded the dye. Only much later (after greater than 30 h), when the cell remnants had undergone a further slow "decay" process, did they stain with trypan blue. In cultures rendered necrotic by lymphotoxin, the killed fibroblasts preserved their morphological integrity but the nuclei became markedly stained with trypan blue. Lymphotoxin was found to be effective only in highly concentrated macrophage and fibroblast cultures. In sparsely populated macrophage cultures, the mediator(s) did not effect cell death but nonetheless exerted marked morphological changes. Vacuoles containing lipids developed and eventually occupied the greater volume of the cytoplasm. Giant lipid droplets were seen leaking out of the macrophage cytoplasm. It is suggested that lymphotoxin does not kill directly, but rather that metabolic products released by the vigorously stimulated target cells cause the necrotic effect in the cultures.

Animals↗