Are “natural killer” cells involved in allograft rejection?

"Natural killer" (NK) effector cells and large granular lymphocytes (LGL) are found inside rat renal allografts during rejection. Their appearance in situ precedes the appearance of cytotoxic T lymphocytes, and concomitantly with their influx in the allograft, the NK activity and the LGL are depleted from the recipient spleen. This suggests that the NK effector cells and the LGL are involved in allograft rejection, although their role(s) among the other in situ inflammatory effector pathways remains to be clarified.     

The “natural killer” cell in the mouse does not require H-2 homology and is not directed against type or group-specific antigens of murine c viral proteins

A number of lymphoma lines were characterized for sensitivity to natural killer (NK) cells present in the spleen in young CBA mice and reactivity with antisera directed against certain C-type virus-determined proteins expressed on the cell surface. Since no correlation was found, it is likely that the target of the NK cell is neither the antigen(s) recognized serologically by mice nor the group-specific antigenic determinants of the viral proteins. Various target and effector cell combinations with regard to H-2 composition did not indicate that H-2 homology is necessary for the NK effect.     

An attempt to produce “pre-T” cell hybridomas and to identify their antigens

With the aim of identifying some of the stages in the development of pre-T cells (cells of the T cell lineage before they enter the thymus), we have produced a large number of hybridomas by the fusion of BALB/c bone marrow cells, bone marrow cells from BALB/c-nu/nu mice, BALB/c fetal liver cells and BALB/c fetal thymocytes with the AKR thymoma BW5147. The hybridomas were selected for the expression of the Thy-1.2 antigen of th3 normal celldonor and for their ability t9produce interleukin 2 (IL 2) upon co-culture with irradiated normal spleen cells. A set of these hybridomas is described in this communication. The hybridomas were then used to immunize rats and to generate monoclonal antibody-producing B cell hybridomas. Most, if not all, of the immunizing hybridomas were derived from pre-T cells as evidenced by the fact that they produce IL 2, and express some of the T cell markers (the Thy-1.2, Ly-1, Ly-2 or L3T4 antigens). The monoclonal antibodies were tested on a panel of pre-T cell hybridomas and on normal cells obtained from spleen, lymph nodes, thymus and bone marrow. The testing was carried out by the microcytotoxicity assay and flow cytometric analysis. Three groups of antibodies could be distinguished. Some antibodies were broadly reactive, being positive with virtually all the clones in the pre-T cell panel and with a substantial fraction of normal lymphoid cells. The identity of the antigens detected by these antibodies remains unknown but they do not seem to correspond to any of the known cell surface markers. Other antibodies reacted only with some of the pre-T cell clones and did not react at all with normal lymphoid cells obtained from adult animals. Finally, other antibodies still reacted only with a minor subpopulation of thymocytes or of thymocytes and bone marrow cells, as well as some of the pre-T cell clones; they did not react with spleen and lymph node cells. These antibodies might be specific for cells in the prethymic phase of the T cell differentiation pathway. They should prove useful for the identification of pre-T cell markers and hence for the isolation of pre-T cells and their functional analysis.     

Bone “mass” and the “mechanostat”: A proposal

The observed fit of bone mass to a healthy animal's typical mechanical usage indicates some mechanism or mechanisms monitor that usage and control the three longitudinal growth, bone modeling, and BMU-based remodeling activities that directly determine bone mass. That mechanism could be named a mechanostat. Accumulated evidence suggests it includes the bone itself, plus mechanisms that transform its mechanical usage into appropriate signals, plus other mechanisms that detect those signals and then direct the above three biologic activities. In vivo studies have shown that bone strains in or above the 1500–3000 microstrain range cause bone modelling to increase cortical bone mass, while strains below the 100–300 microstrain range release BMU-based remodeling which then removes existing cortical-endosteal and trabecular bone. That arrangement provides a dual system in which bone modeling would adapt bone mass to gross overloading, while BMU-based remodeling would adapt bone mass to gross underloading, and the above strain ranges would be the approximate “setpoints” of those responses. The anatomical distribution of those mechanical usage effects are well known. If circulating agents or disease changed the effective setpoints of those responses their bone mass effects should copy the anatomical distribution of the mechanical usage effects. That seems to be the case for many agents and diseases, and several examples are discussed, including postmenopausal osteoporosis, fluoride effects, bone loss in orbit, and osteogenesis imperfecta. The mechanostat proposal is a seminal idea which fits diverse evidence but it requires critique and experimental study.     

Metabolic responses in feline “red” and “white” skeletal muscle to shock and ischemia

In order to investigate possible differences in the reaction to hypoxic conditions between “red” and “white” skeletal muscle, cats were subjected to a 2 h period of either hemorrhagic shock or hind limb tourniquet ischemia, and the hypoxia induced changes were studied in the soleus and lateral gastrocnemius muscles. Muscle biopsies were analysed for ATP, CP, glucose, G 6–P and lactate. Using microelectrodes, the resting membrane potential was repeatedly measured. Both experimental models resulted in increased tissue lactate levels and a successive decrease in the membrane potential of both muscles studied. No reduction of the high energy phosphagen content (ATP+CP) occurred in any of the muscles during shock. The tourniquet ischemia resulted in a 40% reduction of the ATP+CP content in the soleus muscle, whereas in the gastrocnemius muscle no significant reduction occurred. A significant correlation was found between the tissue lactate content and the membrane potential under both conditions and in both muscles studied. It is concluded that “red” muscles are more susceptible to metabolic derangement than “white” muscles during total ischemia, whereas during hypovolemia “red” muscles appear to be protected from early hypoxic damage, probably due to a redistribution of skeletal muscle blood flow.     

Fine structural differences in “fast” and “slow” muscle fibers of the crab

The muscle fibers in the accessory flexor muscle of the crab were examined with the electron microscope. The limiting membrane of the muscle fiber invaginates at many points to form an internal extrafibrillar membranous system between the muscle fibrils. Two types of muscle fiber were found. In one, the fibrils are well separated from each other by an extensive membranous system, the sarcomere lengths are short, and the filaments in the A band are thick. This muscle fiber is the same as the fast fiber previously found physiologically. The other type of muscle fiber has large fibrils poorly separated by a relatively scant system of internal membranes. It has relatively long sarcomeres and comparatively thin filaments in the A band. This type of fiber is the same as the slow fibers described physiologically. Fibers intermediate in type are also found. Nerve terminals with typical synaptic vesicles occur and appear similar on both types of muscle fiber under the electron microscope. Membrane thickenings of nerve ending and muscle fiber also occur at the terminals on both types of muscle fiber. The nerve terminals on the fast fiber are much more easily found and hence more numerous than on the slow fiber. A comparison is made between the invertebrate and vertebrate fast and slow fibers, and some physiological implications of these findings are discussed.     

Genetically modified bone marrow-derived dendritic cells expressing tumor-associated viral or “self” antigens induce antitumor immunity in vivo

The clinical application of synthetic tumor peptide-based vaccines is currently limited to patients with specified major histocompatibility complex (MHC) class I alleles. Such logistic limitations may be overcome using tumor gene-based approaches. Here we describe the effective generation of dendritic cells (DC) expressing tumor peptide-MHC complexes as a result of particle-mediated transfer of genes encoding tumor-associated antigens (TAA). Bone marrow-derived DC were transfected with plasmid DNA encoding the tumor-associated viral antigen E₇ derived from human papilloma virus (HPV) 16. When applied as a vaccine, these genetically modified DC induced antigen-specific CD8⁺ cyto-toxic T lymphocytes (CTL) in vivo and promoted the rejection of a subsequent, normally lethal challenge with an HPV 16-transformed tumor cell line. Of greatest interest, immunization of mice with syngeneic DC genetically modified to enhance their presentation of a constitutive “self” epitope derived from the tumor-suppressor gene product p53 caused a significant reduction in the in vivo growth of a chemically induced p53-positive sarcoma. These results suggest that cancer vaccines consisting of DC genetically modified to express TAA of viral or “self” origin effectively induce antitumor immunity in vivo.     

Ultrastructure of the cilia of thymic cysts in “nude” mice

The ciliary ultrastructure is studied in the ciliated cells of the thymic cysts of the “nude” mouse. The cilium is made up of two segments: the intracellular basal body and the extracellular cilium shaft. The basal body extends in a rootlet and demonstrates three annexes: basal foot, anchoring system and tonofibrillar web. The rootlet, composed of one central and nine peripheral chambers, is closely and constantly associated with smooth endoplasmic reticulum. The classical periodicity of the basal foot can be explained by its internal structure. The anchoring system binds the upper part of the basal body to the cell membrane. The cilium shaft is divided into four segments: implantation base, proximal segment, intermediate segment and tip. The details of particular structures in the implantation base and in the proximal segment are given on transverse and longitudinal sections. In the intermediate part, a peculiar desmosome-like structure, binds some doublets with the ciliary membrane. At the tip level, A tubules end up in an opaque plate and membranes are covered with several intricated cristae.     

The histopathology of tissues in “resistant” and “susceptible” strains of mice infected with a moderate dose of Mycobacterium lepraemurium

A systematic study by light and electron microscopy of tissues from BALB/c and C57BL/6 mice infected subcutaneously with 107 Mycobacterium lepraemurium organisms was carried out at various times throughout the infection. The relatively resistant C57BL/6 mice had an earlier inflammatory response at the site of the infection than did the susceptible BALB/c mice. The infiltration in the former strain contained fibroblast-like cells and epithelioid cells early on in the infection. Few lymphocytes were observed in both strains throughout the infection. The spread of acid-fast bacilli was slower in the resistant strain (C57BL/6). The findings indicated that the rate of cellular infiltration at the infection site and the nature of the cells in the infiltration may determine the outcome of this infection.     

The “Ins” and “Outs” of the Depressive Disorders Section of DSM‐5

In this article, we review and evaluate changes in the depressive disorders section from DSM‐IV to DSM‐5. We describe characteristics of three new depressive disorders: disruptive mood dysregulation disorder, premenstrual dysphoric disorder, and persistent depressive disorder. We also discuss the controversial decision in DSM‐5 to remove the bereavement exclusion from the criteria for major depressive disorder. Next, we review the decision to replace the diagnosis of depressive disorder not otherwise specified with two new diagnoses: other specified depressive disorder and unspecified depressive disorder. Finally, we discuss the inclusion of two novel specifiers in the DSM‐5 depressive disorders section: “with anxious distress” and “with mixed features.” For each of these changes, we examine the relevant research and discuss implications of the changes for research and clinical practice.     

Exploring “personal” and “shared” sense of community identity in Durham City,England

“Personal” and “shared” aspects of sense of community identity are explored in a an established community in Durham City, England. Durham City has a history of over 1,000 years of continuous settlement, and is generally viewed as a stable and relatively harmonious setting. In the study 102 residents responded to a Community Response Questionnaire based on Puddifoot's taxonomy of elements of sense of community. The findings suggest the existence of three underlying “personal” dimensions of Sense of Community Identity (SOCI), namely, “Sense of Personal Support,” “Sense of Personal Contentedness,” and “Personal Involvement,” and three “shared” dimensions of SOCI, namely, “Perceived Community Engagement,” “Perceived Neighborliness,” and “Perceived Settledness.” This article discusses these findings and the prospect of creating a measure for comparative analysis around these dimensions. © 2003 Wiley Periodicals, Inc.