Splenic Hypoplasia Research Articles

PET/CT of the Spleen with Gallium-Oxine-Labeled, Heat-Damaged Red Blood Cells: Clinical Experience and Technical Aspects.

Several scintigraphic techniques have been supplemented or replaced by PET/CT methods because of their superior sensitivity, high resolution, and absolute activity quantification capability. The purpose of this project was the development of a PET tracer for splenic imaging, its radiopharmaceutical validation, and its application in selected patients in whom unclear constellations of findings could not be resolved with established imaging methods. Heat-damaged red blood cells (RBCs) were labeled with [68Ga]gallium-oxine, which was produced from [68Ga]gallium and 8-Hydroxyquinoline (oxine) on an automated synthesizer. Ten patients underwent [68Ga]gallium-oxine-RBC-PET/CT for the classification of eleven unclear lesions (3 intra-, 8 extrapancreatic). [68Ga]gallium-oxine and [68Ga]gallium-oxine-labeled RBCs could be synthesized reproducibly and reliably. The products met GMP quality standards. The tracer showed high accumulation in splenic tissue. Of the 11 lesions evaluated by PET/CT, 3 were correctly classified as non-splenic, 6 as splenic, 1 as equivocal, and 1 lesion as a splenic hypoplasia. All lesions classified as non-splenic were malignant, and all lesions classified as splenic did not show malignant features during follow-up. PET/CT imaging of the spleen with [68Ga]gallium-oxine-labeled, heat-damaged RBCs is feasible and allowed differentiation of splenic from non-splenic tissues, and the diagnosis of splenic anomalies.

A case of pneumococcal meningitis complicated by intervertebral discitis, spinal epidural abscess, and paravertebral abscess with splenic hypoplasia

A case of pneumococcal meningitis complicated by intervertebral discitis, spinal epidural abscess, and paravertebral abscess with splenic hypoplasia

The Congenital Absence of the Portal Vein

Congenital absence of the portal vein (CAPV) is a rare defect often accompanied by other abnormalities such as heart defect, skeletal anomalies and / or liver tumors [1]. We describe here a case of CAPV revealed by an upper gastrointestinal tract hemorrhage in a child aged 02 years and 8 months. The esogatro-duodenal fibroscopy revealed the presence of Esophageal varices grade II, abdominal ultrasound revealed a large liver with no visualization of the spleen. Subsequent abdominal computed tomography revealed the presence of a spleno-mesaraic trunk measuring 7 mm in anteroposterior diameter receiving the inferior and superior mesenteric vein and a small splenic vein draining by dilated peri-gastric and peri-esophageal leads. Associated with splenic hypoplasia and portal trunk atresia. The rest of the malformative assessment was negative

Toxicity of a methotrexate metronomic schedule in Wistar rats

Metronomic chemotherapy is a relevant strategy that uses low doses of antineoplastic drugs for sustained periods to control tumor growth, an alternative frequently utilized in veterinary patients. This work aimed to evaluate the toxic effects of a metronomic oral dose of methotrexate (MTX) for 45 days in tumor-free Wistar rats when compared with control animals. Clinical alterations, body weight, food, and water intake were monitored daily, and bone marrow suppression, hematological, biochemical, and histopathological analyses were performed at three points (days 30, 45, and 60). MTX-treated animals did not demonstrate severe systemic involvement. At 30 days, compared with control animals, MTX-treated animals showed significant leukocytosis (11.9 ± 2.3 vs. 7.8 ± 0.2 106/μL; P < .05) and augmentation of immature myeloid populations from bone marrow (9.0 ± 0.8 vs. 6.5 ± 1.5%; P < .05), and at 60 days, treated animals showed significant neutrophilia (35.0 ± 11.0 vs. 23.00 ± 3.0%; P < .05), depletion of bone marrow lymphocytes (8.2 ± 0.7 vs. 11.5 ± 1.9%; P < .05), and immature myeloid populations (7.2 ± 0.7 vs. 8.3 ± 0.6%; P < .05). At a histopathological level, splenic hypoplasia and respiratory inflammatory lesions were significant when compared with control animals, presenting mild to moderate myelotoxicity, immune suppression, and associated clinical compromise that persisted beyond treatment withdrawal. This suggested that MTX metronomic toxicity should not be neglected owing to the observed residual side-effects and special care should be taken regarding myelosuppression.

Prophylactic antibiotic treatment exacerbates Graft vs. Host Disease-induced bone marrow failure and spleen hypoplasia

Abstract Acute graft vs. host disease (aGVHD) is a major complication following hematopoietic stem cell transplantation. Preclinical and clinical studies suggest aGVHD may be potentiated by gut damage and translocation of intestinal microbiota following toxic, pre-transplant conditioning protocols. We recently reported that aGVHD-induced bone marrow (BM) failure and splenic hypoplasia develops in the absence of gut damage suggesting that intestinal bacteria may not be required for disease pathogenesis. Objective Determine whether prophylactic gut decontamination with broad spectrum antibiotics (Abx) affects the onset and/or severity of aGVHD-induced BM and spleen damage. Methods Syngeneic (Bl6) or allogeneic (Balb/c) CD4+CD25−T cells (5×106 cells) were injected into NK cell-depleted Bl6 RAG1−/− recipients. Prior to T cell transfer, RAG1−/− mice received water (ab libitum) containing aspartame (Asp) or an Abx cocktail containing Asp, neomycin and vancomycin for 7 days prior to and following T-cell transfer. Results Treatment of allogeneic mice with Abx reduced colonic bacterial load by more than 20-fold when compared to their Asp-treated counterparts. Abx treatment also resulted in large and significant reductions in BM- and spleen-residing T cells and myeloid cells as well as circulating erythrocytes, platelets and hematocrit when compared to Asp treated mice. These Abx-induced alterations were associated with significant increases (~4-fold) in serum IL-6 levels compared to Asp-treated mice. Conclusions Prophylactic Abx treatment exacerbates aGVHD-induced BM failure and spleen hypoplasia.

A Case of Invasive Pneumococcal Infection in a Patient with Splenic Hypoplasia

A Case of Invasive Pneumococcal Infection in a Patient with Splenic Hypoplasia

T cell-mediated bone marrow and splenic hypoplasia in a mouse model of acute graft vs. host disease

Abstract A major limitation with use of hematopoietic stem cell transplantation to treat relapsing hematological malignancies is the development of a potentially lethal, multi-organ inflammatory disorder called acute graft versus host disease (aGVHD). Acute GVHD-associated bone marrow (BM) suppression and lymphoid tissue (LT) hypoplasia creates protracted immunodeficiency that greatly increases the risk of infections, bleeding and death. Objective We wished to define the role that allogeneic CD4+ T cells play in a mouse model of aGVHD-associated BM and LT aplasia that does not require lethal myeloablative conditioning. Methods Allogeneic CD4+CD25−T cells (0.5×106 cells) obtained from Bl6-H2-Ab1bm12 (Bl6-BM12) donor mice were adoptively transferred into sub-lethally irradiated C57Bl6 (Bl6) recipients. Mice were monitored daily for clinical signs of aGVHD. Results Adoptive transfer of allogeneic but not syngeneic T cells induced a time-dependent loss of survival and remarkable reductions of cellularity in the BM and spleen. Virtually all allogeneic mice developed severe anemia at 15 days post transfer. Flow cytometric analyses revealed dramatic and significant losses of CD4+ T cells, myeloid cells and NK cells in the BM and spleen indicating BM suppression and spleen hypoplasia. Interestingly, we observed little immune cell infiltration in the lungs, liver and skin of allogeneic recipients and no evidence of disease in any tissue of syngeneic mice. These data suggest that the major target tissues in this model of aGVHD are BM and spleen. Conclusions When taken together, these data demonstrate that adoptive transfer of allogeneic CD4+ T cells into sub-lethally irradiated recipients induces aGVHD-associated immunodeficiency.

A T cell-specific knockout reveals an important role for protease-activated receptor 2 in lymphocyte development.

Activation of protease-activated receptor-2 (PAR2) expressed by T cells has been linked to the bone loss associated with periodontitis. We generated PAR2 conditional-null mice and crossed these with mice expressing Cre recombinase under control of the Lck proximal promoter, to produce T cell-specific PAR2-null mice in order to further study the cellular mechanism involved in periodontitis. Here we report that efficient deletion of PAR2 in thymocytes isolated from T cell-specific PAR2-null mice resulted in thymic and splenic hypoplasia and a reduction in the cells of the cortex and a loss of distinction between the cortex and the medulla of the thymus. FACS analysis confirmed significant reductions in CD4 and CD8 double negative (DN3 and DN4) sub-populations, as well as double positive and single positive T cells, in T cell-specific PAR2-null mice compared to Cre expressing PAR2 wild-type mice. The proportion of annexin V positive and propidium iodide negative cells was increased in CD4 and CD8 double negative, double positive and single positive T cells from T cell-specific PAR2-null mice. No change in the proportion of Ki67 positive cells was observed in sections of thymus from T cell-specific PAR2-null mice, suggesting that the depletion of T cell sub-populations in T cell-specific PAR2-null mice resulted from increased apoptosis rather than reduced proliferation. Together, these results demonstrate that PAR2 plays an important and previously unrecognised anti-apoptotic role in T cell development and suggest that the PAR2 conditional-null mouse will be an important resource for determining tissue and cell specific effects of PAR2.

Streptococcus pneumoniae induced purpura fulminans in a patient with splenic hypoplasia

Streptococcus pneumoniae induced purpura fulminans in a patient with splenic hypoplasia

Congenital Splenic Hypoplasia in an Elderly Patient.

Congenital Splenic Hypoplasia in an Elderly Patient.

Hypoplasia of the spleen: Review of pathogenesis, diagnosis, and potential clinical implications

Context:Splenic aplasia is seen when the spleen is congenitally absent, has been surgically removed, or becomes atrophic secondary to episodes of arterial/venous occlusion, which result in splenic infarction. This rare condition is caused by a heterogenous group of diseases, which may present a wide spectrum of clinical manifestations. Splenic hypoplasia is defined as reduction in splenic mass and or functions caused by incomplete splenic development or secondary parenchymal involution. Splenic infarction may be clinically silent and only discovered incidentally during abdominal exploration for other conditions.Case Report:We present an unusual case of hypoplastic spleen with calcifications, which was preoperatively found during radiologic workup for gastric carcinoma. An 88-year-old woman presented with coffee-ground emesis. Her past medical history was only significant for atrial fibrillation. Esophagogastroduodenoscopy demonstrated gastric carcinoma, for which a subtotal gastrectomy was planned. Preoperative computed tomography scan showed a hypoplastic spleen with calcifications in the left upper quadrant. Symptoms of immunologic deficiency were not present. During laparotomy, an atrophied and calcified spleen was identified and left in situ. The patient made an uneventful postoperative recovery. Splenic hypoplasia is an unique entity, which may be seen in the setting of atrial fibrillation and abdominal malignancy.Conclusion:Splenic hypoplasia may be detected incidentally during radiologic workup or abdominal exploration. Abdominal symptoms or immunologic deficiency are not always present.

A splicing mutation in the novel mitochondrial protein DNAJC11 causes motor neuron pathology associated with cristae disorganization, and lymphoid abnormalities in mice.

Mitochondrial structure and function is emerging as a major contributor to neuromuscular disease, highlighting the need for the complete elucidation of the underlying molecular and pathophysiological mechanisms. Following a forward genetics approach with N-ethyl-N-nitrosourea (ENU)-mediated random mutagenesis, we identified a novel mouse model of autosomal recessive neuromuscular disease caused by a splice-site hypomorphic mutation in a novel gene of unknown function, DnaJC11. Recent findings have demonstrated that DNAJC11 protein co-immunoprecipitates with proteins of the mitochondrial contact site (MICOS) complex involved in the formation of mitochondrial cristae and cristae junctions. Homozygous mutant mice developed locomotion defects, muscle weakness, spasticity, limb tremor, leucopenia, thymic and splenic hypoplasia, general wasting and early lethality. Neuropathological analysis showed severe vacuolation of the motor neurons in the spinal cord, originating from dilatations of the endoplasmic reticulum and notably from mitochondria that had lost their proper inner membrane organization. The causal role of the identified mutation in DnaJC11 was verified in rescue experiments by overexpressing the human ortholog. The full length 63 kDa isoform of human DNAJC11 was shown to localize in the periphery of the mitochondrial outer membrane whereas putative additional isoforms displayed differential submitochondrial localization. Moreover, we showed that DNAJC11 is assembled in a high molecular weight complex, similarly to mitofilin and that downregulation of mitofilin or SAM50 affected the levels of DNAJC11 in HeLa cells. Our findings provide the first mouse mutant for a putative MICOS protein and establish a link between DNAJC11 and neuromuscular diseases.

Overwhelming Pneumococcal Sepsis in a Patient with Splenic Hypoplasia

Department of Infectious Diseases, Yokohama Municipal Citizen’s HospitalA 58-year-old female was admitted due to severe sepsis and multi-organ failure with a fulminant purpuric rash.Meropenem, vancomycin and levofloxacin were administered, although no focus of infection was detected. However,computed tomography revealed a profoundly hypoplastic spleen, and a blood smear detected Howell-Jolly bodies.Blood cultures grew Streptococcus pneumoniae (serotype 22F) three hours after admission. The patient was finallydiagnosed as overwhelming pneumococcal sepsis with hyposplenism precipitated by splenic hypoplasia. Cliniciansshould pay attention to the splenic size and Howell-Jolly bodies in cases of sepsis of unknown origin.Keywords: Streptococcus pneumoniae, splenic hypoplasia, Howell-Jolly bodies, purpura fulminans, Pneumovaxµ 23,23-valent pneumococcal polysaccharide vaccineCASE REPORTA 58-year-old female was admitted to YokohamaMunicipal Citizen’s Hospital due to severe sepsis, andmulti-organ failure in April 2013. She developedgeneral fatigue, diarrhea and a high-grade fever of42°C on the day before hospitalization. On the day ofadmission, the patient also developed dyspnea. She hada past surgical history of osteosarcoma at the age of 23years and breast cancer at the age of 49 years requiringa mastectomy and axillary lymphadenectomy, followedby adjuvant chemotherapy and hormone therapy forfive years. She had not been previously vaccinated withthe 23-valent pneumococcal polysaccharide vaccine(PPSV23).In the emergency room, her vital signs were asfollows: blood pressure was 99/73mmHg, heart ratewas 100 beats/min, respiratory rate was 45 breaths/min, body temperature was 33.3°C and Glasgow ComaScale was E3V4M6 (total 13/15).Physical examination revealed purpura on her faceand extremities (Figure 1), whereas other systemexaminations were unrevealing. Despite a whole bodycomputed tomography (CT) scan, urine Gram staining,and rapid diagnostic testing (group A streptococcus,Streptococcus pneumoniae, and Influenza) from thepatient’s throat, it was not possible to detect theAuthor for correspondence: Kenichiro YaitaDepartment of Infectious Diseases, Yokohama Municipal Citizen’s Hospital, 56 Okazawa-cho, Hodogaya-ku,Yokohama, Kanagawa 240-8555, JapanE-mail: kyaita81@gmail.comReceived for publication 26 September 2013 and accepted in revised form 29 January 2014© 2014 The Japan Primary Care AssociationGeneral Medicine 2014, vol. 15, no. 1, p. 68–71.

An Autopsy Case of Fulminent Pneumococcal Infection, Meningitis and Multiple Organ Failure Resulting from Splenic Hypoplasia

An Autopsy Case of Fulminent Pneumococcal Infection, Meningitis and Multiple Organ Failure Resulting from Splenic Hypoplasia

A Recurrent Case of Fulminant Pneumococcal Infection due to Splenic Hypoplasia Under Use of Pneumococcal Vaccine

A Recurrent Case of Fulminant Pneumococcal Infection due to Splenic Hypoplasia Under Use of Pneumococcal Vaccine

Serological and pathological assessment of lymphoid organs in chicks fed with graded levels of fermented and unfermented cassava diets

Despite the myriad of investigations in literature on cassava utilization in domestic chickens, its effects on the avian specific humoral immune system still remains elusive. This study investigated the effects of graded levels of fermented (F) and unfermented (UF) cassava diets on the lymphoid organs and its subsequent humoral immunological response in domestic chicks. One hundred day-old Yaffa White cockerels were randomly divided into five groups (A to E) of twenty birds each. The replacement of maize with 0%, 20%, 30%, fermented or unfermented cassava root meal was on a quantitative basis in each group fed for 5 weeks. All other ingredients remained constant. The mean body weight in different cassava treated groups (CTGs) showed no significant difference (P>0.05) compared with the control. The bursa and thymic weights showed both decrease and increase significant difference (P<0.05). There was significant decrease in the IBD antibody titers of CTGs compared with the control at week 5. Macroscopically, mild to moderate enlargement and atrophy of bursa of Fabricius, with petechiation of cortical surfaces of the thymus were observed. Microscopically, lesions such as interfollicular edema, interfollicular fibrosis, follicular atrophy, lymphofollicular hypoplasia, dystrophic epithelium, thickened splenic capsule, splenic lymphoid hypoplasia, thymic lymphoid hypoplasia, diffuse medullary thymic haemorrhages and Myoid cells proliferation were the consistent histopathological changes in all the CTGs. In conclusion, this study demonstrated that cassava inclusion feeds could cause subtle sublethal effects to the lymphoid organs of domestic chickens, and consequently lead to vaccine failure when it is administered for a long period of time. Keywords : Lymphoid organs, fermented and unfermented cassava, serology, pathology

Evaluation of the efficiency of confirming Howell-Jolly body in peripheral erythrocytes and splenic hypoplasia on CT to screen for a group at high risk of fulminant pneumococcal infection

Evaluation of the efficiency of confirming Howell-Jolly body in peripheral erythrocytes and splenic hypoplasia on CT to screen for a group at high risk of fulminant pneumococcal infection

Characterization of the Pituitary Tumor Transforming Gene 1 Knockout Mouse Retina

Recent gene expression studies on mouse models for retinal degeneration identified deregulation of Pituitary tumor transforming gene 1 (Pttg1) as a potential susceptibility factor involved in photoreceptor cell death. Pttg1 is a transcription regulatory protein involved in sister chromatid segregation, and Pttg1(-/-) mice exhibit testicular and splenic hypoplasia, thymic hyperplasia, aberrant cell cycle progression, chromosome instability, and impaired glucose homeostasis leading to diabetes, particularly in older males. Due to Pttg1 deregulation in dystrophic retinas, we characterized Pttg1(-/-) retinas using Hematoxylin and Eosin (H&E) staining, immunohistochemistry (IHC), and electroretinography (ERG). Seven month old Pttg1(-/-) mice were also examined for a diabetic retinopathy phenotype using Fluorescein Angiography (FA) to test for neovascularization. Our data reveal that up to 9 months of age, Pttg1(-/-) retinas have a healthy morphology and normal photoreceptor function. This study lays the groundwork for further investigation into the relevance of Pttg1 in retinal dystrophy.

Вплив дефіциу гена pttg-1 на розвиток аутоімунних процесів у мишей

PTTG (Pituitary Tumour Transforming gene-1) is a protoncogene which is expressed in testes, thick and thin bowel, and in activated lymphocytes. Protein product of this gene is involved in mitosis and cell cycle regulation. Lack of pttg in mice ( pttg-КО ) leads to thymic hyperplasia and splenic hypoplasia. Specific aim of this work was to investigate presence of anti-dsDNA, anti-core histons antibodies and also check affinity of producated antibodies of wild type mice and mice wit lack of pttg-1. The level of antibo­dies to single strand, double strand DNA and core histons of wild type and mice lacking pttg were investigated. Affinity of autoantibodies to double strand native DNA was studied. The revealed changes of autoantibodies level to double strand DNA and core histones suggest that the lack of pttg-1 causes the development of autoimmune processes. Keywords : pttg-1, autoimmune processes, affinity.

52-jährige Patientin mit akuter Schocksymptomatik und Purpura fulminans

We report a 52-year-old female patient admitted with fever, chills, and myalgias since the previous day. On the day of admission she had a generalized seizure. The patient had no previous illnesses. Laboratory investigations showed consumptive coagulopathy with clinical manifestations of shock and development of multiple organ failure. Pneumococci were detected in blood cultures. Furthermore the skin showed purpura fulminans all over. The patient died within 24 h after admission in the intensive care unit. On autopsy, in addition to adrenal and myocardial hemorrhages, hypoplasia of the spleen was found. Fulminant pneumococcal sepsis is a life-threatening disease that occurs in patients with risk factors like splenic hypoplasia or asplenia. Sometimes a fulminant pneumococcal sepsis may be the first clinical manifestation of a hitherto unknown splenic hypoplasia. In this context the general recommendation of vaccination against pneumococci in patients with risk factors like splenic hypoplasia or asplenia, in patients older than 60, and in children from 2 months onward has to be emphasized.