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Journal of Ultrasound in Medicine :... Mar 2015To determine the feasibility of spleen stiffness measurement in the evaluation of portal hemodynamics in patients undergoing transjugular intrahepatic portosystemic... (Clinical Trial)
Clinical Trial
Sonographic assessment of spleen stiffness before and after transjugular intrahepatic portosystemic shunt placement with or without concurrent embolization of portal systemic collateral veins in patients with cirrhosis and portal hypertension: a feasibility study.
OBJECTIVES
To determine the feasibility of spleen stiffness measurement in the evaluation of portal hemodynamics in patients undergoing transjugular intrahepatic portosystemic shunt (TIPS) placement.
METHODS
We prospectively correlated the spleen stiffness as measured by the shear wave velocity with the portal pressure and portosystemic gradient in patients undergoing TIPS procedures. Twenty-three consecutive patients referred for placement of a TIPS were enrolled. Included in our study were 19 patients in whom a spleen stiffness measurement was obtained before, immediately after, and 1 to 3 days after placement. Spleen stiffness was measured by calculating the Young modulus estimated from the shear wave velocity. A 2-tailed nonparametric Mann-Whitney U test was used to assess statistically significant differences in spleen stiffness measurement after TIPS placement, and regression analysis was used to correlate spleen stiffness measurement with portal pressure.
RESULTS
After TIPS placement, the spleen stiffness measurement increased, with a mean increase in the Young modulus ± SD of 6.54 ± 6.29 kPa in 42% of patients (8 of 19). In the remaining 58% (11 of 19), the spleens became softer after TIPS placement (Young modulus decreased by 9.57 ± 8.82 kPa). Eight patients, including 5 with concurrent embolization or thrombosis of competitive shunts, had increased spleen stiffness. The mean change in the median spleen stiffness before and after TIPS placement between the patients with and without competitive shunts was statistically significantly different (P < .04, nonparametric Mann-Whitney U test). There was no measurable correlation between spleen stiffness measurement and portal pressure before and after TIPS placement.
CONCLUSIONS
This study demonstrates the feasibility of a noninvasive spleen stiffness measurement, which could complement conventional sonography with additional functional information in patients undergoing TIPS procedures.
Topics: Adult; Aged; Combined Modality Therapy; Diagnosis, Differential; Elastic Modulus; Elasticity Imaging Techniques; Embolization, Therapeutic; Fibrosis; Humans; Hypertension, Portal; Middle Aged; Portal Vein; Portasystemic Shunt, Transjugular Intrahepatic; Reproducibility of Results; Sensitivity and Specificity; Spleen
PubMed: 25715365
DOI: 10.7863/ultra.34.3.443 -
PLoS Medicine May 2021A very large biomass of intact asexual-stage malaria parasites accumulates in the spleen of asymptomatic human individuals infected with Plasmodium vivax. The mechanisms...
BACKGROUND
A very large biomass of intact asexual-stage malaria parasites accumulates in the spleen of asymptomatic human individuals infected with Plasmodium vivax. The mechanisms underlying this intense tropism are not clear. We hypothesised that immature reticulocytes, in which P. vivax develops, may display high densities in the spleen, thereby providing a niche for parasite survival.
METHODS AND FINDINGS
We examined spleen tissue in 22 mostly untreated individuals naturally exposed to P. vivax and Plasmodium falciparum undergoing splenectomy for any clinical indication in malaria-endemic Papua, Indonesia (2015 to 2017). Infection, parasite and immature reticulocyte density, and splenic distribution were analysed by optical microscopy, flow cytometry, and molecular assays. Nine non-endemic control spleens from individuals undergoing spleno-pancreatectomy in France (2017 to 2020) were also examined for reticulocyte densities. There were no exclusion criteria or sample size considerations in both patient cohorts for this demanding approach. In Indonesia, 95.5% (21/22) of splenectomy patients had asymptomatic splenic Plasmodium infection (7 P. vivax, 13 P. falciparum, and 1 mixed infection). Significant splenic accumulation of immature CD71 intermediate- and high-expressing reticulocytes was seen, with concentrations 11 times greater than in peripheral blood. Accordingly, in France, reticulocyte concentrations in the splenic effluent were higher than in peripheral blood. Greater rigidity of reticulocytes in splenic than in peripheral blood, and their higher densities in splenic cords both suggest a mechanical retention process. Asexual-stage P. vivax-infected erythrocytes of all developmental stages accumulated in the spleen, with non-phagocytosed parasite densities 3,590 times (IQR: 2,600 to 4,130) higher than in circulating blood, and median total splenic parasite loads 81 (IQR: 14 to 205) times greater, accounting for 98.7% (IQR: 95.1% to 98.9%) of the estimated total-body P. vivax biomass. More reticulocytes were in contact with sinus lumen endothelial cells in P. vivax- than in P. falciparum-infected spleens. Histological analyses revealed 96% of P. vivax rings/trophozoites and 46% of schizonts colocalised with 92% of immature reticulocytes in the cords and sinus lumens of the red pulp. Larger splenic cohort studies and similar investigations in untreated symptomatic malaria are warranted.
CONCLUSIONS
Immature CD71+ reticulocytes and splenic P. vivax-infected erythrocytes of all asexual stages accumulate in the same splenic compartments, suggesting the existence of a cryptic endosplenic lifecycle in chronic P. vivax infection. Findings provide insight into P. vivax-specific adaptions that have evolved to maximise survival and replication in the spleen.
Topics: Adolescent; Adult; Asymptomatic Infections; Female; Humans; Indonesia; Malaria, Vivax; Male; Middle Aged; New Guinea; Plasmodium vivax; Prospective Studies; Reticulocytes; Spleen; Splenectomy; Young Adult
PubMed: 34038413
DOI: 10.1371/journal.pmed.1003632 -
Immunology May 2016The precise mechanisms responsible for immunosenescence still remain to be determined, however, considering the evidence that disruption of the organization of primary...
The precise mechanisms responsible for immunosenescence still remain to be determined, however, considering the evidence that disruption of the organization of primary and secondary lymphoid organs results in immunodeficiency, we propose that this could be involved in the decline of immune responses with age. Therefore, we investigated the integrity of the splenic microarchitecture in mice of increasing age and its reorganization following immune challenge in young and old mice. Several differences in the anatomy of the spleen with age in both the immune and stromal cells were observed. There is an age-related increase in the overall size of the white pulp, which occurs primarily within the T-cell zone and is mirrored by the enlargement of the T-cell stromal area, concurrent to the distinct boundary between T cells and B cells becoming less defined in older mice. In conjunction, there appears to be a loss of marginal zone macrophages, which is accompanied by an accumulation of fibroblasts in the spleens from older animals. Furthermore, whereas the reorganization of the white pulp is resolved after several days following antigenic challenge in young animals, it remains perturbed in older subjects. All these age-related changes within the spleen could potentially contribute to the age-dependent deficiencies in functional immunity.
Topics: Aging; Animals; Chemokine CCL19; Chemokine CCL21; Male; Mice; Mice, Inbred C57BL; Spleen; T-Lymphocytes
PubMed: 26840375
DOI: 10.1111/imm.12590 -
PloS One 2021The purpose of this study is to examine the effect of repeated cocaine administration on the whole body of rats. Rats (male, 6 weeks old, Sprague Dawley) were injected...
The purpose of this study is to examine the effect of repeated cocaine administration on the whole body of rats. Rats (male, 6 weeks old, Sprague Dawley) were injected intraperitoneally with cocaine (50 mg/kg) once a day for 1, 3 or 7 days, and major organs (heart, liver, lung, brain, kidney, spleen) were excised from the sacrificed animals. During autopsy, we found a reduction in spleen size, but not other organs, in cocaine-administered rats as compared to control rats. This reduction became to be noticed at 3 day and easily perceived at 7 day. No marked changes were observed in other organs examined. H&E and EMG staining showed a tendency for a decrease in the number of red blood cells (RBCs) as well as an increase in collagen fibers in the spleens of rats treated repeatedly with cocaine. Transcriptome analysis indicated that repeated cocaine administration depletes RBCs from the spleen. Immunoblot analysis showed that cocaine increases the phosphorylation of myosin light chain (MYL) as well as the levels of transgelin, both of which are involved in the contraction of myofibrils. Collectively, these results show that repeated cocaine administration results in sustained contraction of the spleen, which leads to the release of RBCs from the spleen into circulation.
Topics: Animals; Cocaine; Gene Expression Regulation; Male; Organ Size; Rats; Rats, Sprague-Dawley; Spleen; Transcriptome; Vasoconstrictor Agents
PubMed: 34086815
DOI: 10.1371/journal.pone.0252853 -
Annals of Surgery Feb 1991The modern era for splenic surgery for injury began in 1892 when Riegner reported a splenectomy in a 14-year-old construction worker who fell from a height and presented... (Review)
Review
The modern era for splenic surgery for injury began in 1892 when Riegner reported a splenectomy in a 14-year-old construction worker who fell from a height and presented with abdominal pain, distension, tachycardia, and oliguria. This report set the stage for routine splenectomy, which was performed for all splenic injury in the next two generations. Despite early reports by Pearce and by Morris and Bullock that splenectomy in animals caused impaired defenses against infection, little challenge to routine splenectomy was made until King and Schumacker in 1952 reported a syndrome of "overwhelming postsplenectomy infection" (OPSI). Many studies have since demonstrated the importance of the spleen in preventing infections, particularly from the encapsulated organisms. Overwhelming postsplenectomy infection occurs in about 0.6% of children and 0.3% of adults. Intraoperative splenic salvage has become more popular and can be achieved safely in most patients by delivering the spleen with the pancreas to the incision, carefully repairing the spleen under direct vision, and using the many adjuncts to suture repair, including hemostatic agents and splenic wrapping. Intraoperative splenic salvage is not indicated in patients actively bleeding from other organs or in the presence of alcoholic cirrhosis. The role of splenic replantation in those patients requiring operative splenectomy needs further study but may provide significant long-term splenic function. Although nonoperative splenic salvage was first suggested more than 100 years ago by Billroth, this modality did not become popular in children until the 1960s or in adults until the latter 1980s. Patients with intrasplenic hematomas or with splenic fractures that do not extend to the hilum as judged by computed tomography usually can be observed successfully without operative intervention and without blood transfusion. Nonoperative splenic salvage is less likely with fractures that involve the splenic hilum and with the severely shattered spleen; these patients usually are treated best by early operative intervention. Following splenectomy for injury, polyvalent pneumococcal vaccine decreases the likelihood of OPSI and should be used routinely. The role of prophylactic penicillin is uncertain but the use of antibiotics for minor infectious problems is indicated after splenectomy.
Topics: Adult; Female; Humans; Radiography; Spleen; Splenectomy; Wounds and Injuries
PubMed: 1992948
DOI: 10.1097/00000658-199102000-00002 -
PloS One 2013Our previous results with flight (FLT) mice showed abnormalities in thymuses and spleens that have potential to compromise immune defense mechanisms. In this study, the...
Our previous results with flight (FLT) mice showed abnormalities in thymuses and spleens that have potential to compromise immune defense mechanisms. In this study, the organs were further evaluated in C57BL/6 mice after Space Shuttle Atlantis returned from a 13-day mission. Thymuses and spleens were harvested from FLT mice and ground controls housed in similar animal enclosure modules (AEM). Organ and body mass, DNA fragmentation and expression of genes related to T cells and cancer were determined. Although significance was not obtained for thymus mass, DNA fragmentation was greater in the FLT group (P<0.01). Spleen mass alone and relative to body mass was significantly decreased in FLT mice (P<0.05). In FLT thymuses, 6/84 T cell-related genes were affected versus the AEM control group (P<0.05; up: IL10, Il18bp, Il18r1, Spp1; down: Ccl7, IL6); 15/84 cancer-related genes had altered expression (P<0.05; up: Casp8, FGFR2, Figf, Hgf, IGF1, Itga4, Ncam1, Pdgfa, Pik3r1, Serpinb2, Sykb; down: Cdc25a, E2F1, Mmp9, Myc). In the spleen, 8/84 cancer-related genes were affected in FLT mice compared to AEM controls (P<0.05; up: Cdkn2a; down: Birc5, Casp8, Ctnnb1, Map2k1, Mdm2, NFkB1, Pdgfa). Pathway analysis (apoptosis signaling and checkpoint regulation) was used to map relationships among the cancer-related genes. The results showed that a relatively short mission in space had a significant impact on both organs. The findings also indicate that immune system aberrations due to stressors associated with space travel should be included when estimating risk for pathologies such as cancer and infection and in designing appropriate countermeasures. Although this was the historic last flight of NASA's Space Shuttle Program, exploration of space will undoubtedly continue.
Topics: Animals; DNA Fragmentation; Feeding Behavior; Female; Gene Expression Profiling; Gene Expression Regulation; Mice; Models, Biological; Oncogene Proteins; Organ Size; Signal Transduction; Space Flight; Spleen; Thymus Gland; Weightlessness
PubMed: 24069384
DOI: 10.1371/journal.pone.0075097 -
Acta Biochimica Polonica 2015An interesting example of extradermal deposition of melanin in vertebrates, notably in mammals, is splenic melanosis. In particular, if the phenomenon of splenic...
An interesting example of extradermal deposition of melanin in vertebrates, notably in mammals, is splenic melanosis. In particular, if the phenomenon of splenic melanosis is correlated with hair or skin pigmentation, it must reflect the amount and perhaps the quality of pigment produced in hair follicle melanocytes. The present paper is our first study on splenic pigmentation in mice of phenotype agouti. We used untreated mixed background mice C57BL/6;129/SvJ (black - a/a, agouti - A/a, A/A), and as a control - black C57BL/6 and agouti fur from 129/SvJ mice, Mongolian gerbils (Meriones unguiculatus) and golden hamsters (Mesocricetus auratus). After euthanasia skin and spleen was evaluated macroscopically, photographed and collected for further analysis using Fontana-Masson and hematoxylin-eosin staining and electron paramagnetic resonance (EPR) at X-band. Spleens of the agouti mice revealed splenic melanosis but were slightly weaker pigmented than their black counterparts, while the presence of pheomelanin was difficult to determine. The fur of both phenotypes was of similar melanin content, with the same tendency as in the spleens. The contribution of pheomelanin in the agouti fur was on the border of detectability by EPR. Histological and EPR analysis confirmed the presence of melanin in the melanotic spleens. The shape of the EPR signal showed a dominance of eumelanin in fur and in melanized spleens in both phenotypes of mice. Therefore, splenic melanosis does reflect the hair follicle pigmentation not only in black, but also in agouti mice.
Topics: Animals; Electron Spin Resonance Spectroscopy; Female; Gerbillinae; Hair; Hair Follicle; Male; Melanins; Melanocytes; Melanosis; Mesocricetus; Mice; Mice, Inbred C57BL; Phenotype; Skin Pigmentation; Species Specificity; Spleen
PubMed: 26291042
DOI: 10.18388/abp.2015_1053 -
Frontiers in Immunology 2019To compare microscopic and immunologic features in the spleens of patients who died of pulmonary hemorrhage and shock caused by leptospirosis (11 cases) or...
To compare microscopic and immunologic features in the spleens of patients who died of pulmonary hemorrhage and shock caused by leptospirosis (11 cases) or Gram-positive/-negative bacterial septic shock (10 cases) to those from control spleens (12 cases from splenectomy). Histological features in the red pulp and white pulp were analyzed using archived samples by a semi quantitative score. Immunohistochemistry was used for the recognition of immune cell markers, cytokines, caspase-3 and antigens. The control group differed significantly from the leptospirosis and septic shock patients which demonstrate strong similarities: diffuse congestion in the red pulp with a moderate to intense infiltration of plasma cells and polymorphonuclear cells; follicles with marked atrophy; high density of CD20 cells; low density of NK, TCD4 and active caspase-3 positive cells and strong expression of IL-10; leptospirosis patients had higher S100 and TNF-α positive cells in the spleen than the other groups. The results suggest that an immunosuppressive state develops at the terminal stage of severe leptospirosis with pulmonary hemorrhage and shock similar to that of patients with septic shock, with diffuse endothelial activation in the spleen, splenitis, and signs of disturbance in the innate and adaptive immunity in the spleen. The presence of leptospiral antigens in 73% of the spleens of the leptospirosis patients suggests the etiological agent contributes directly to the pathogenesis of the lesions. Our results support therapeutic approaches involving antibiotic and immunomodulatory treatments for leptospirosis patients and suggest that leptospirosis patients, which are usually young men with no co-morbidities, form a good group for studying sepsis and septic shock.
Topics: Adult; Antigens, Bacterial; Female; Humans; Immune Tolerance; Leptospira; Leptospirosis; Male; Middle Aged; Retrospective Studies; Severity of Illness Index; Shock, Septic; Spleen
PubMed: 31114579
DOI: 10.3389/fimmu.2019.00920 -
The Anatomical Record Dec 1997The reticular framework of the white pulp (WP) and marginal zone (MZ) consists of reticulum cells and reticulin fibers. The antigenic heterogeneity of the reticular...
BACKGROUND
The reticular framework of the white pulp (WP) and marginal zone (MZ) consists of reticulum cells and reticulin fibers. The antigenic heterogeneity of the reticular framework is well documented in the mouse and rat spleen. The aim of the present study is to characterize the reticular framework of the WP and MZ of the human spleen.
METHODS
Nine surgically resected human spleens were investigated. Five of the nine spleens were perfused. Formalin-fixed materials were embedded in paraffin and serial sections prepared for hematoxylin-eosin, silver staining, and immunohistochemical examination. Electron and immuno-electron microscopy were also applied. Using confocal laser scanning microscopy, the reticular framework was analyzed three-dimensionally.
RESULTS
The reticulin fibers of the framework were immunostained for type IV collagen in the WP and MZ. The WP was three-dimensionally delimited by the alpha-smooth muscle actin (alpha-SMA)-positive reticulum cells. In the WP, the distribution of alpha-SMA-positive reticulum cells formed the reticular framework of the periarteriolar lymphoid sheath (PALS). They also ensheathed the reticulin fibers. Interdigitating cells (IDCs) were scattered throughout the framework. A few IDCs attached to the framework. In the lymph follicle (LF), reticulum cells were not alpha-SMA-positive. The mesh of follicular dendritic cells (FDCs) was found in the germinal center. In places, the reticulin fibers were involved in the mesh of the FDCs and covered by the cytoplasm of FDCs. In the MZ, alpha-SMA-positive reticulum cells were arranged in a mesh pattern and ensheathed the fine reticulin fibers.
CONCLUSION
The reticular framework of the PALS, LF, and MZ is specialized into heterogeneous components in the human spleen. The heterogeneity of the framework may induce the segregation of T and B lymphocytes.
Topics: Actins; Adult; Aged; Arterioles; Child, Preschool; Collagen; Dendritic Cells; Female; Humans; Immunohistochemistry; Male; Microscopy, Confocal; Microscopy, Immunoelectron; Middle Aged; Reticulin; Spleen
PubMed: 9415456
DOI: 10.1002/(SICI)1097-0185(199712)249:4<486::AID-AR8>3.0.CO;2-P -
Blood Feb 2019Thrombosis is a frequent, life-threatening complication of systemic infection associated with multiple organ damage. We have previously described a novel mechanism of...
Thrombosis is a frequent, life-threatening complication of systemic infection associated with multiple organ damage. We have previously described a novel mechanism of inflammation-driven thrombosis induced by Typhimurium infection of mice. Thrombosis in the liver develops 7 days after infection, persisting after the infection resolves, and is monocytic cell dependent. Unexpectedly, thrombosis was not prominent in the spleen at this time, despite carrying a similar bacterial burden as the liver. In this study, we show that thrombosis does occur in the spleen but with strikingly accelerated kinetics compared with the liver, being evident by 24 hours and resolving rapidly thereafter. The distinct kinetics of thrombosis and bacterial burden provides a test of the hypothesis that thrombi form in healthy vessels to trap or remove bacteria from the circulation, often termed immunothrombosis. Remarkably, despite bacteria being detected throughout infected spleens and livers in the early days of infection, immunohistological analysis of tissue sections show that thrombi contain very low numbers of bacteria. In contrast, bacteria are present throughout platelet aggregates induced by in vitro. Therefore, we show that thrombosis develops with organ-specific kinetics and challenge the universality of immunothrombosis as a mechanism to capture bacteria in vivo.
Topics: Animals; Liver; Mice; Mice, Inbred C57BL; Salmonella Infections; Salmonella typhimurium; Spleen; Thrombosis
PubMed: 30401709
DOI: 10.1182/blood-2018-08-867267