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[Mechanism of stimulation of spleen mononuclear cells by gram-positive bacterial peptidoglycan].

Periodontal disease is a chlonic inflammatory disorder, and for which oral microbes are supposed to be responsible. Among oral microbials, gram-negative bacterias have been studied extensively in relation to periodontal disease for their pathogenicity due to their lipopolysaccharide (LPS), exocellular enzymes or bacterial toxin. As for gram-positive bacterials, it has been reported recently that gram-positive bacteria can elicit immunological responses, and this may be responsible for the initiation and/or development of periodontal disease. However, precise mechanisms of bacterial action, especially of gram-positive bacteria, on periodontal disease have not been elucidated yet. In this experiment, therefore, gram-positive bacteria (S. epidermidis), peptidoglycan subunits of S. epidermidis (SEPS) and muramyl dipeptide (MDP) were used to investigate for their activities to stimulate spleen mononuclear cells to replicate and produce various kinds of cytokines. Immunological responsibilities of various strains of mice were explored to investigate the difference of defence of mechanisms. Following results were obtained. (1) S. epidermidis itself showed a extremely low cell-mediated activity to stimulate the replication of spleen mononuclear cells in contrast to E. coli. Staphylococcal phage lysate and SEPS stimulated remarkally the replication of spleen mononuclear cells. (2) The stimulation of spleen mononuclear cells was accompanied by the production of interleukin 3 (IL-3) and colony stimulating factor (CSF), but interleukin 2(IL-2) was not produced as in the case of E. coli. (3) Analysis of cell surface antigens revealed the increase of the numbers of Ia+ and Mac-2+ bone marrow cells following stimulation of spleen mononuclear cells with SEPS. However, T or B cells were not increased. (4) Macrophage-depleted and antisera Ia-treated spleen mononuclear cells showed a marked decrease of replicating activity of spleen mononuclear cells. (5) Among the various strains of mice tested C3H/HeN, Balb/c, AKR, DBA/2, C57BL/6, ddY, C3H/HeJ, MRL/lpr and showed a high immunological responses, but Balb/c did not. C3C/HeJ and MRL/lpr also lacked immunological reactivity. These results suggest that proliferative response of lymphocyte with peptidoglycan in gram-positive bacterium is very important for infection and its defensive reaction against gram-positive bacteria.

Acetylmuramyl-Alanyl-Isoglutamine↗

Paul-Bunnell antigen in lymphoma and leukemia spleens.

Lymphoid cells obtained from spleens of patients with lymphomas or leukemias were studied for the presence of heterophile (Paul-Bunnell (P-B)) antigen. A mixed agglutination (MA) test was established utilizing monolayers of cells attached to poly-L-lysine-coated wells of plastic U plates. After incubation of the monolayers with infectious mononeucleosis (IM) sera, indicator cells, sheep, or trypsinized bovine erythrocytes were added. The results were assessed according to sedimentation patterns of the indicator cells on the monolayers. Positive MA reactions were shown to be due to specific binding of P-B antibodies to the corresponding antigens on the spleen cells. Positive results were obtained with 15 of 37 spleens from patients with Hodgkin's disease, 5 of 8 lymphoma spleens, 4 of 15 chronic myelocytic leukemia spleens and 2 of 4 chronic lymphocytic leukemia spleens. Only 2 of 25 spleens from patients with various other diseases and 1 of 26 apparently normal thymus specimens gave positive results. This study confirmed demonstration of P-B antigen in lymphoma and leukemia by means of absorption experiments, which was reported previously.

Agglutination Tests↗

[Wandering spleen in children: report of 4 cases].

The occurrence of a wandering spleen is rarely referred to in the pediatric surgical literature. In the last three years we treated four patients with this anomaly. The first case had an acute abdominal problem associated to a wandering mass with spleen characteristics. The ultrasonography has confirmed the absence of spleen from its proper place. In the second case it was detected a mass with the same features of the first patient associated with choledochal cyst. In this case the ultrasound has demonstrated that spleen was the referred mass. In the third case a patient was submitted to a surgery with the preoperative diagnosis of ovarian torsion. The patient had an associated osteogenesis imperfecta. During the operation it was found that spleen was the referred mass. In the fourth patient the preoperative diagnosis was "abdominal mass". It is given an emphasis to the preservation of the spleen in wandering spleen, mainly in childhood, due to its immunological importance.

Child↗

Progressive ankylosis (ank/ank) in mice: an animal model of spondyloarthropathy. III. Proliferative spleen cell response to T cell mitogens.

Murine progressive ankylosis is a spontaneous disorder of mice resulting from a homozygous recessive genetic defect (ank/ank) which produces an inflammatory arthritis of peripheral and axial joints eventually resulting in ankylosis of these joints. This disorder resembles the human spondyloarthropathies clinically, radiographically and histologically. Various studies in humans with spondyloarthropathies have described defects of cellular immunity but these results are conflicting. We measured the spleen cell response to mitogen in ank/ank mice and in normal littermates. The spleen cell response to the T cell mitogens phytohaemagglutinin and concanavalin A was decreased in ank/ank mice compared with their normal littermates. The response to the B cell mitogen lypopolysaccharide was normal in both ank/ank mice and normal littermates. Serum from ank/ank mice did not inhibit spleen cell responses to mitogen. Ank/ank spleen cells were not inhibitory of normal spleen cell responses to mitogens. Addition of irradiated normal spleen cells to ank/ank spleen cells did not restore the mitogen responses to normal. It is possible that the ank/ank gene results in the phenotypic expression of an abnormal or decreased cell product involved in T cell proliferation. Several recently described cytokines could be potential candidates for this product.

Animals↗

Kinetics of early and late spleen colony development.

The kinetics of spleen colony development were studied with special emphasis upon the self-replicative capacity of CFU-S, which are responsible for the early- or late-appearing spleen colonies, and upon CFU-S migration in the days following transplantation. It was found that, while the spleen colonies had a much lower daughter CFU-S content at eight days than at 11 or 12 days, many of the 8-day colonies remained in the spleen to become 12-day colonies which had many daughter CFU-S. In addition, it was found that large numbers of CFU-S were present in the splenic space between the colonies. Evidence was developed that these "intercolonial space" CFU-S were the founders of many of the late-appearing spleen colonies and that many or all of them were transported from the bone marrow to the spleen via the blood at varying times after the transplantation. Approximately one-half of the day-12 colony founders were found to arrive in the spleen after the third posttransplantation day.

Aging↗

Tumor-specific suppressor T-cells which inhibit the in vitro generation of cytolytic T-cells from immune and early tumor-bearing host spleens.

Spleen cells from DBA/2 mice, after immunization with syngeneic P815 mastocytoma cells and Corynebacterium parvum, respond to P815 in vitro with a brisk, secondary-type generation of cytotoxic cells. This cytotoxicity is mediated by antigen-specific T-lymphocytes and correlates with resistance to in vivo challenge. This model confirms the observations of previous investigators made in semisyngeneic hosts using an in vivo transfer model. Spleen cells from "early" tumor-bearing hosts (TBHs), 7-12 days after intradermal (i.d.) inoculation of 10(6) P815 cells alone, made a similar, but generally higher, cytotoxic T-lymphocyte (CTL) response in vitro. Spleen cells from "late" TBHs (18-28 days) completely suppressed the in vitro CTL response of immune cells (e.g., from 71% specific release in controls down to 8% at an effector: target ratio of 40:1). Early i.d. TBH spleen cells, because of their higher level response, appeared to be resistant to this suppression (85% release for controls and 84% when suppressor cells were added at 40:1). By testing early TBH CTL at lower effector: target ratios, however, suppression by late TBH spleen cells could be readily demonstrated. When TBHs were inoculated s.c. instead of i.d. or with lower doses of tumor cells, responses were lower and susceptibility of splenic CTLs to suppression was increased. At intermediate times after tumor inoculation (14-20 days), spleen cells from TBHs still can respond in vitro, but they are completely suppressed by spleen cells from late TBHs. The suppressor cells are antigen-specific, radiation-sensitive, Thy1+ cells.

Animals↗

[Effect of the spleen cells from partially splenectomized and partially hepatectomized mice on the proliferation of hepatocytes in the regenerating liver of syngeneic recipients].

Cells of mouse spleen obtained 48 h after foster splenectomy, foster hepatectomy, resection of 2/3 of spleen or 36 h after resection of 2/3 of liver were introduced intravenously into partially hepatectomized (resection of 2/3 or 1/4 of liver) syngeneic recipients. Cells of regenerating spleen sharply inhibited the mitotic activity of cells of the recipient liver following resection of 1/4 of liver 48 h after the operation and introduction of cells. Inhibition proved to be dose-dependent: it became apparent when 30 million cells were introduced, increased at a dose of 60 million cells and remained at the same level at higher doses. Division of hepatocytes after resection of 1/4 of liver was inhibited by spleen cells taken in the donors 36 h after partial hepatectomy. Spleen cells of intact and pseudo-operated donors had no such ability. Introduction of 60 million of cells of the regenerating spleen and of the spleen of partially hepatectomized animals into recipients with resection of 2/3 of liver did not inhibit reliably the division of hepatocytes, thus indicating the dependence of inhibition on the level of suppressors in the organism. Resection of a major part of liver was accompanied by a greater decrease in the activity of endogenous suppressors which could not be recovered by the introduced cells. Inhibition of cell division by suppressors was not organ specific. Suppressors inhibited proliferation in liver irrespective of the site of operation.

Animals↗

[Morphology and function of the human spleen. Enzyme histochemical and electron microscopy studies of the splenic lymphatic vessels, nerves and connective tissue structures].

Many questions concerning the morphology of the spleen have been cleared up in the last 20 years by the application of new methods of investigation, especially electron microscopy and enzyme histochemistry. With but a few exceptions, however, only the splenic parenchyma (the red and white pulp) were studied. Such special structures of the human spleen as nerves, lymphatic vessels and their supporting tissue, which may play an important role in the coordination and integration of the different functions of the white pulp (secondary lymphatic organ) and the red pulp (blood filter), were hardly ever studied with modern techniques. Investigating these structures light and electron microscopically and enzyme histochemically it was attempted to complete our present knowledge of the histology of the human spleen. In addition, by comparing the study of special altered spleens with experimental data it was attempted to clarify the importance of these structures for the physiology and pathology of the spleen. A total of 151 normal and pathologically altered spleens from the bioptic and autopsy material of the Pathological Institute of the University of Kiel were examined. In addition to conventional light microscopy the spleens were investigated enzyme histochemically and cytochemically, fluorescence microscopically and electron microscopically. The following enzyme reactions were done: Alkaline and acid phosphatase, alpha-naphthylacetate-esterase, naphthol-AS-acetate-esterase, 5'-nucleotidase, ATPase, and acetylcholinesterase. The various enzyme reactions were sometimes done in combination and reticulum and collagenous fibers were investigated by a subsequent staining of argyrophilic fibers. The fine localization of the 5'-nucleotidase activity was studied ultrahistochemically. Adrenergic nerve fibers were investigated fluorescence microscopically using the glyoxylic acid method.

Connective Tissue↗

Absence of B stem cells in spleens of chickens fed the androgen analog mibolerone.

Bursa-derived stem cells in the spleens of chickens treated with the androgen analog mibolerone or with cyclophosphamide and in the spleens of untreated controls were examined by a transplantation technique. Spleen cells from syngeneic donors 2-20 weeks old were transferred to syngeneic cyclophosphamide-treated recipients, and the immunocompetence of the recipients was tested 5 weeks after the transfer by antigenic stimuli with sheep erythrocytes and Brucella abortus. Spleens of mibolerone-treated chickens failed to reconstitute the immunologic capability of cyclophosphamide-treated recipients in a manner similar to spleen cells from normal donors. Spleens of cyclophosphamide-treated donors did not contain stem cells. Stem cells were detected in the spleens of untreated controls as young as 2 weeks old; activity was highest after the 13th week of age.

Animals↗

Pathology of the lymph node and spleen in systemic mast cell disease.

The spleen and lymph node are two of the most common organs involved in systemic mast cell disease (SMCD). However, SMCD infiltrates in the spleen and lymph node have a broad spectrum of morphological patterns which can make it difficult to recognize the diagnosis, especially when specimens are examined from patients in whom SMCD is not suspected. We reviewed the pathological features of 16 spleen and 23 lymph node specimens from 19 patients which represented all available material from a series of 58 Mayo Clinic patients with SMCD. The purpose of this study was to investigate the pathological manifestations of SMCD involvement in the spleen and lymph node and to address difficulties in differential diagnosis. All compartments of the spleen and lymph node were found to be affected by SMCD. SMCD lesions in the spleen were found in a paratrabecular (92%), parafollicular (69%), follicular (15%), and a diffuse red pulp (8%) distribution. In the lymph node, mast cell infiltrates affected the paracortex (88%), the parafollicular region (50%), the follicles (25%), the medullary cords (13%), and the sinuses (6%). Mast cells were frequently found in a perivascular location, and associated eosinophilia was common. Because of the broad spectrum of histological manifestations of SMCD in the spleen and lymph node, a wide range of differential diagnoses is discussed including follicular lymphoma, T-cell lymphoma, monocytoid B-cell hyperplasia and lymphoma, Kaposi's sarcoma, and Langerhans' cell granulomatosis.

Diagnosis, Differential↗

Syngeneic male graft rejection by B6 female mice primed with spleen and testes of Sxr and Sxr' mice.

Presence or absence of the mammalian male-specific H-Y transplantation antigen was investigated in Sxr and Sxr' mice. Groups of C57BL/6 (B6) female mice were primed with spleen cells or testicular homogenates of such mice and were subsequently grafted with syngeneic male skin. Median graft survival times (MSTs) were compared with the MSTs of control groups: (i) unprimed B6 females, (ii) B6 females primed with B6 female spleen, and, (iii) B6 females primed with B6 male spleen or testes. The MSTs of the groups primed with B6 male and Sxr spleen were significantly shorter than, and those of the groups primed with B6 female and Sxr' spleen similar to the MST of unprimed females. The MSTs of groups of B6 female mice primed with testicular homogenates of B6, Sxr, and Sxr' males did not differ from the MST of unprimed B6 females. Taken together, this indicates that spleen of B6, and Sxr males carry the H-Y transplantation antigen, while the antigen is lacking on spleen cells of B6 females and Sxr' males. The results of priming with testis are interpreted such that (i) either do testes of B6, Sxr and Sxr' males lack the antigen, or, (ii) priming with testes homogenates renders B6 females unresponsive to H-Y of male grafts.

Animals↗

The immunodepressive effect of Friend virus III. Effects on spleen T cells.

We have examined various T lymphocyte functions in the spleens of mice infected 4 days previously with Friend viurs (FV) in order to analyse its effect on the antibody response. We have found (a) that infection does not reduce the percentage of T lymphocytes in the spleen, nor their ability to respond to PHA, (b) that infected spleen cells mediate allogeneic augmentation of the primary response to SRBC in vitro, even though their own depressed response cannot be restored via the allogeneic effect, and (c) that infected spleen cells restore responses to SRBC by both allogeneic and syngeneic spleen cell cultures depleted of T lymphocytes. These results suggest that FV does not affect spleen T lymphocyte proliferation of helper function. Since macrophages from infected spleens cooperate normally in the response to SRBC in vitro, we conclude that the immune defect resides in the B lymphocytes.

Animals↗

Unusual presentation on the right side of ectopic testicular spleen.

An unusual case of right-side testicular spleen is presented. Although described as early as 1889, all cases except one were described to have occurred on the left side. This report documents a second case of extra-testicular spleen occurring on the right side. Since ectopic spleen is an extra-testicular mass and invariably benign, it must be recognized and considered in the primary differential diagnosis of any intrascrotal mass. Since ectopic intrascrotal spleen occurs in the majority of clinical cases under 20 years of age, a preoperative diagnosis of ectopic spleen will prevent possibly unnecessary radical testiculectomy in this age group. Radioactive sulphur colloid will localize in the ectopic spleen, and therefore this modality can be used as an additional preoperative diagnostic tool. Since ectopic testicular spleen was found in up to 25% of all reported cases during orchiopexy and/or herniorrhaphy repair, this entity must be familiar to general and urological surgeons.

Adult↗

[A study of the T-lymphocytes and their subsets in the peripheral and spleen using OK and Leu series monoclonal antibodies--especially patients with idiopathic portal hypertension (IPH) and liver cirrhosis].

The T lymphocytes and their subsets in the peripheral blood and spleen of the patients with idiopathic portal hypertension (IPH) and liver cirrhosis were analysed using OK and Leu series monoclonal antibodies. The healthy subjects showed no difference between the OK series (OKT3, OKT4, OKT8) and the Leu series (Leu3a, Leu2a). In the patients with IPH or liver cirrhosis, the percentages of OKT3 and Leu 4 positive lymphocytes (pan T), and OKT4 and Leu3a positive lymphocytes (H/I T) were similar, but the percentages of OKT8 and Leu2a positive lymphocytes (S/C T) in the patients with IPH were slightly decreased. The changes in the T lymphocyte subsets differed among the patients, but the patients with IPH and liver cirrhosis showed a slight decrease in the mean number of H/I T and a slight increase in that of S/C T after splenectomy. Pan T and H/I T in the IPH cases were similar to those of the normal spleen, but S/C T was slightly higher than that of the normal spleen. The distribution of the lymphocytes in the spleen examined by the ABC method showed that in the normal spleen, the OKT-positive lymphocytes were concentrated around the artery. The B1-positive lymphocytes were distributed on the outer portion of the OKT3-positive lymphocytes aggregate in a mantle shape. The distribution of the OKT4-positive subset and that of the OKT3-positive subset were almost the same. OKT8-staining was seen sporadically in the medullary cord, but there were slightly more OKT8-positive lymphocytes in the medullary cord in these spleens than in the normal spleen.

Adult↗

[Centroblastic and centrocytic centroblastic malignant lymphomas, predominantly splenic (or primary of the spleen). Anatomo-clinical study of 17 cases].

Seventeen cases of splenic centroblastic-centrocytic or centroblastic lymphoma are reported. A large splenomegaly is discovered in all these cases as the prominent symptom. For this reason, all these cases can be considered as primary lymphoma of the spleen. Splenectomy is done in 7 cases for diagnosis a period of 2 to 8 months after the discovery of the splenomegaly. In these patients, no bone marrow biopsy was performed before splenectomy. In 8 other cases, the diagnosis of follicular lymphoma is proposed on a bone marrow biopsy performed with the aim to disclose an etiology for the splenomegaly. In 3 of these cases, a lymph node (2 cases) or a tonsil biopsy (1 case) discover a tumoral localization before the splenectomy. In the 2 last cases, the diagnosis is recognized on a lymph node biopsy. The most important clinical and biological data are compared for these 17 patients. The anatomopathological data are described. In 15 cases, a multimicronodular pattern is recognized on the spleen section. The 2 other cases express a multimacronodular pattern. The weight of the spleen is comprised between 450 and 3,350 g, with only 6 spleens weighing less than 1,000 g. The spleens with multimicronodular pattern correspond to a follicular centroblastic centrocytic lymphoma of low grade of malignancy in the Kiel-Lennert classification. The 2 multimacronodular spleens exhibit the histological aspect of a polymorphous centroblastic lymphoma of a high grade of malignancy. The equivalent of these histological types are given in the Working Formulation. The diagnosis with others diseases of the spleen is discussed. For fourteen patients, the follow-up is available. Six patients are alive, with an evolution of many years. Because of the few number of cases, it is not possible to correlate the histological subtypes according to Kiel or to the WF, and the clinical stage with the evolution. To perform such correlation, a multicentric study should be organized.

Adult↗

Venous segmentation of the human spleen. A corrosion cast study.

Partial splenectomy is possible because of vascular segmentation of this organ. Although interest has focused upon arterial supply, this study shows similar venous segmentation. Emerging splenic veins in excess of 1.7 mm at the hilum of ten unembalmed spleens were injected with different colors of modified Batson's compound, and corrosion casts were made. In four additional spleens, alternate veins and arteries were injected. Ten spleens had two primary segments (lobes); four had three lobes. Half of these lobes were further subdivided into two segments. Lobes and segments extended through the full thickness of the spleen. Relatively avascular interlobar planes were always approximately perpendicular to the longitudinal axis of the spleen, whereas intersegmental planes were more variable. Both interlobar and intersegmental planes frequently corresponded to marginal notches. When arteries and veins were both injected, similar segmentation was noted. Venous drainage did not overlap arterial segments, indicating that veins are intrasegmental. These results indicate that the surgical unit of the spleen can be based upon surgically accessible vessels at the hilum of the spleen. Identification of segmental vessels could permit salvage of a larger amount of splenic tissue than would be possible if only lobar vessels were identified.

Adult↗

[The role of the spleen in immunosuppression and the effects of splenectomy on prognosis in gastric cancer patients].

To elucidate the role of the spleen on the immunosuppression in gastric cancer patients, mechanism of the induction of suppressor cells in the spleen was investigated. Studies of tissue distribution of T cells using monoclonal antibodies revealed that spleen contained much higher proportion of OKT8 reactive T cells as compared with those in regional lymphnodes without metastasis. Lymphocytes released from the spleen during perfusion were taken to be representative of recirculating lymphocytes. Suppressor precursor cells were found to exist predominantly in perfusate from the spleen, while spontaneously activated suppressor cells were in the residual lymphocytes in the spleen after perfusion. Culture supernatants from splenic adherent cells induced suppressor cell activities as well as sera from splenic venous blood. These results suggest that suppressor precursor cells which could be mobilized slowly was more comparable to splenic lymphocytes and might be matured by factors released from splenic adherent cells, partly moving into peripheral blood. Furthermore, the effect of splenectomy on the prognosis of gastric cancer patients was investigated in randomized controlled trial. The patients who underwent total gastrectomy and had main location of the tumor on lesser curvature region were divided into two groups at random; splenectomy (+) and splenectomy (-) groups. A suggestive prolongation of survival time was observed in splenectomy (+) group. Thus, spleen seem to contribute to the immunosuppression in gastric cancer patients and splenectomy may lead to better prognosis.

Adult↗

Specific suppression of the immune response by HGG tolerant spleen cells. I. Parameters affecting the level of suppression.

After adoptive transfer, the spleen cells from mice made tolerant to human gamma-globulin (HGG) specifically suppress the immune response of normal spleen cells. However, this suppressive activity in the spleen cells of tolerant mice is only present for a brief period after treatment with tolerogen. Spleen cells from animals injected 10 days earlier with tolerogen reduce the immune response of an equal number of normal spleen cells by 75%. Spleen cells from mice made tolerant 40 days previously are, however, no longer suppressive, even though they remain completely unresponsive. These data suggest that active suppression of antigen-reactive cells is not the mechanism responsible for maintaining tolerance to HGG, but rather is only transiently associated with the tolerant state. Further evidence in favor of the separation of the tolerant state from suppressive activity is that complete suppression of the normal spleen cell response requires either a high ratio of tolerant to immune competent cells or a delay in the antigenic challenge of the reconstituted recipients. By contrast, such manipulations are not required to demonstrate the complete unresponsiveness of the tolerant cells after adoptive transfer.

Animals↗