Adult ; Antibodies, Monoclonal ; analysis ; DNA Nucleotidylexotransferase ; metabolism ; Female ; Follow-Up Studies ; Humans ; Keratins ; immunology ; Male ; Middle Aged ; Prognosis ; Thymoma ; metabolism ; pathology ; surgery ; Thymus Neoplasms ; metabolism ; pathology ; surgery

OBJECTIVE: To investigate the relationship between DNA degradeation and postmortem interval. METHODS: dUTP was transferred to 3'terminal of DNA by using terminal deoxynucleotidyl transferase (TDT), then the reminders of dUTP after experimental reaction, as indicator of quantity of DNA degradation, were detected. RESULTS: The reminders of dUTP were decreasing along with the postmortem interval. CONCLUSION Postmortem DNA degradation may be used in postmortem interval judgment.
Animals ; Cell Nucleus/metabolism* ; Clinical Enzyme Tests/methods* ; DNA/metabolism* ; DNA Nucleotidylexotransferase/metabolism* ; Kidney/metabolism* ; Liver/metabolism* ; Male ; Postmortem Changes ; Pyrophosphatases/metabolism* ; Rats ; Rats, Sprague-Dawley ; Spectrophotometry, Ultraviolet ; Spleen/metabolism* ; Time Factors

Adult ; Antigens, CD20 ; metabolism ; Carcinoma ; metabolism ; pathology ; DNA Nucleotidylexotransferase ; metabolism ; Diagnosis, Differential ; Female ; Follow-Up Studies ; Humans ; Keratins ; metabolism ; Lymphoma ; metabolism ; pathology ; Male ; Middle Aged ; Necrosis ; Seminoma ; metabolism ; pathology ; Thymoma ; metabolism ; pathology ; surgery ; Thymus Neoplasms ; metabolism ; pathology ; surgery ; Tuberculosis ; pathology

Adult ; Biopsy ; CD3 Complex ; metabolism ; DNA Nucleotidylexotransferase ; metabolism ; Female ; Humans ; Leukemia, Biphenotypic, Acute ; metabolism ; pathology ; Lymph Nodes ; metabolism ; pathology ; Neck ; PAX5 Transcription Factor ; metabolism ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; metabolism ; pathology

Adult ; Burkitt Lymphoma ; metabolism ; pathology ; CD3 Complex ; metabolism ; DNA Nucleotidylexotransferase ; metabolism ; Diagnosis, Differential ; Female ; Granulosa Cell Tumor ; metabolism ; pathology ; Humans ; Ki-67 Antigen ; metabolism ; Leukocyte Common Antigens ; metabolism ; Ovarian Neoplasms ; metabolism ; pathology ; surgery ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; metabolism ; pathology ; surgery ; Sarcoma, Myeloid ; metabolism ; pathology

Objective: Brain and muscle ARNT-like protein 1 (BMAL1) is a core component of hepatocyte molecular clock and plays an important role in the regulation of other related rhythmic genes in the body through a transcriptional-translational feedback loop in molecular circadian oscillations. Therefore, the aim of this study was to investigate the role of BMAL1 in the rat periodontitis-induced liver injury. Methods: Twelve male Wistar rats were divided into the control group and the periodontitis group according to the random number table method. The rats in the control group were untreated. The periodontitis models were established by ligating the necks of the bilateral maxillary first molars in the periodontitis group rats. After 8 weeks, periodontal clinical indexes of rats in both groups were examined and executed. Micro-CT scans of the maxilla were performed and levels of the alveolar bone resorption were analyzed. Pathological changes in periodontal and liver tissue of rats in two groups were detected by HE and oil red O staining. Biochemical kits were used to detect glutamic-oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), total cholesterol (TC) and triglycerides (TG) in serum. The gene and protein expression levels of BMAL1, nuclear factor kappa-B (NF-κB) and tumor necrosis factor-α (TNF-α) in liver tissue were measured by real time fluorescent quantitative-PCR (qRT-PCR), immunohistochemistry (IHC) and Western blotting (WB) assays. Apoptosis was detected in liver tissues by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) kit staining. Results: The results of HE staining of maxillary first molars and micro-CT results of maxillary bones showed that alveolar bone resorption was significant in the periodontitis group of rats. The liver histopathology results showed infiltrated inflammatory cells in the liver tissue, disorganized liver cords and a large number of lipid droplets formed in the hepatocytes of the periodontitis group compared with the control group. The results of serum biochemical assay showed that the levels of GOT [(62.77±2.59) U/L], GPT [(47.54±1.04) U/L], TC [(3.19±0.23) mmol/L] and TG [(1.11±0.09) mmol/L] in the serum of rats with periodontitis were significantly higher than that in the control group respectively [GOT: (38.66±2.47) U/L, GPT: (31.48±1.57) U/L, TC: (1.60±0.05) mmol/L and TG: (0.61±0.09) mmol/L](P=0.003, P=0.001, P=0.002, P=0.038). qRT-PCR results showed that the mRNA expression level of BMAL1 was significantly decreased in liver tissue of the periodontitis group [(0.60±0.04)%] compared to the control group [(1.01±0.07)%] (t=4.80, P=0.009), while the mRNA expression levels of NF-κB and TNF-α [(1.62±0.12)%, (2.69±0.16)%] were significantly increased compared to the control group [(1.00±0.03)%, (1.03±0.16)%] (P=0.008, P=0.002); IHC results showed that the protein expression level of BMAL1 in liver tissue of the periodontitis group (averaged optical density, AOD) (11.58±2.15) was down-regulated compared to the control group (AOD) (22.66±1.67) (P=0.015), while NF-κB and TNF-α (AOD) (31.77±2.69, 24.31±2.32) were up-regulated compared to the control group (AOD) (19.40±1.82, 11.92±0.94) (P=0.019, P=0.008). WB results showed that the protein expression level of BMAL1 in liver tissue was down-regulated in the periodontitis group [(0.63±0.10)%] compared to the control group [(1.00±0.06)%] (t=3.19, P=0.033), while NF-κB and TNF-α [(1.61±0.12)%, (2.82±0.23)%] were up-regulated compared to the control group [(1.00±0.12)%, (1.00±0.11)%] (P=0.022, P=0.002). TUNEL staining showed increased apoptotic cells in the liver tissue of the periodontitis group of rats compared to the control group. Conclusions: Periodontitis may induce liver injury by down-regulating the BMAL1 expression levels in liver tissue, which in turn activates NF-κB signaling molecules, leading to the elevated levels of inflammation and apoptosis in rat liver.
Animals ; Male ; Rats ; Alanine Transaminase/metabolism* ; ARNTL Transcription Factors/metabolism* ; Aspartate Aminotransferases/metabolism* ; Biotin/metabolism* ; Bone Resorption ; Brain ; Chemical and Drug Induced Liver Injury, Chronic ; Cholesterol ; DNA Nucleotidylexotransferase/metabolism* ; Muscles/metabolism* ; NF-kappa B/metabolism* ; Periodontitis ; Rats, Wistar ; RNA, Messenger/metabolism* ; Triglycerides ; Tumor Necrosis Factor-alpha/metabolism*

Basic Helix-Loop-Helix Transcription Factors ; metabolism ; Chromosome Aberrations ; DNA Nucleotidylexotransferase ; metabolism ; Humans ; Immunoglobulin Light Chains ; metabolism ; Immunoglobulin Light Chains, Surrogate ; Lymphoma, B-Cell ; genetics ; metabolism ; pathology ; Lymphoma, T-Cell ; genetics ; metabolism ; pathology ; Membrane Glycoproteins ; metabolism ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; genetics ; metabolism ; pathology ; Proto-Oncogene Proteins ; metabolism ; T-Cell Acute Lymphocytic Leukemia Protein 1

Indolent T-lymphoblastic proliferation has been rarely reported in the upper aerodigestive tract. The lymphoid cells associated with this condition have the morphological and phenotypical features of immature thymocytes. However, their pathogenesis and biology are unknown. We present an unusual type of tumor infiltrating lymphocytes in a case with hepatocellular carcinoma, presumed to be a T-lymphoblastic proliferation. A 58-yr-old female patient presented with indigestion and a palpable epigastric mass. The abdominal computed tomography revealed a mass in the S6 region of the liver. A hepatic segmentectomy was performed. Microscopic examination showed dense isolated nests of monomorphic lymphoid cells within the tumor. Immunohistochemically, the lymphoid cells were positive for CD3, terminal deoxymucleotide transferase (TdT) and CD1a. In addition, they showed dual expression of CD4 and CD8. The polymerase chain reaction used to examine the T-cell antigen receptor gamma gene rearrangement showed polyclonal T-cell proliferation. This is the second case of hepatocellular carcinoma combined with indolent T-lymphoblastic proliferation identified by an unusual tumor infiltrating lymphocytes.
Antigens, CD3/metabolism ; Antigens, CD4/metabolism ; Antigens, CD8/metabolism ; Carcinoma, Hepatocellular/*diagnosis/pathology/secondary ; DNA Nucleotidylexotransferase/metabolism ; Female ; Humans ; Liver Neoplasms/*diagnosis/immunology/pathology ; Lymphocytes, Tumor-Infiltrating/*pathology ; Mastectomy, Segmental ; Middle Aged ; Precursor Cells, T-Lymphoid/*pathology ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/complications/metabolism/*pathology ; Tomography, X-Ray Computed

OBJECTIVETo study the clinicopathologic features, immunohistochemical findings and prognosis of precursor lymphoblastic lymphoma/acute lymphoblastic leukemia (LBL/ALL).

METHODSOne hundred and fifty-three cases of LBL/ALL were retrospectively analyzed. Immunohistochemical study was carried out. The pathologic findings were correlated with Ann Arbor tumor stage, Ki-67 index, other clinical parameters (including mediastinum/bone marrow involvement, hepato-splenomegaly, age and gender of the patients) and the survival data.

RESULTSStaining for TdT and CD99 was positive in 79.1% (121/153 cases) and 96.3% (131/136 cases), respectively. The cases were categorized into three groups according to the immunohistochemical findings, as follows: precursor T-cell, precursor B-cell and undefined. T-LBL/ALL accounted for 69.3% (106/153 cases) of all of the cases. The male-to-female ratio was 2.4:1 (including 75 males and 31 females). The median age at diagnosis was 17.5 years (ranged from 2 years to 68 years). Ninety-two patients (86.8%) presented with peripheral lymphadenopathy and 59 of them (55.7%) had mediastinal masses. Ninety-one cases (85.8%) were in stage III or IV at diagnosis. The 1-year and 5-year survival rates in patients with T-LBL/ALL were 36.1% and 8.1%, respectively. Patients older than 25 years and those presented in stage III or IV suggested a poor prognosis (P = 0.049 and 0.001, respectively). On the other hand, 29 of the 153 cases (19.0%) belonged to B-LBL/ALL. The median age of the patients was 14 years (ranged from 9 months to 75 years). The male-to-female ratio was 1.6:1 (including 18 males and 11 females). Seventeen patients (58.6%) presented with peripheral lymphadenopathy and 13 of them (44.8%) had involvement of bone marrow or peripheral blood. Mediastinal involvement was found only in 5 cases (17.2%). Twenty-one patients (72.4%) were in stage III or IV at diagnosis. The 1-year and 5-year survival rates were 53.3% and 36.7%, respectively. The remaining 11.7% cases (18/153 cases) were categorized as undefined type, with a negative staining for the following immuno-markers including: CD3ε/CD3, CD45RO, CD79a, CD20, MPO, CD5, CD56, cyclin D1, cytokeratin, neuron-specific enolase, chromogranin A and synaptophysin. The median age of the patients was 15.5 years (ranged from 4 to 53 years). The male-to-female ratio was 2.6:1 (including 13 males and 5 females). The percentage of T-LBL/ALL patients with mediastinal masses were significantly higher than that of B-LBL/ALL cases (P = 0.0003). There was no significant difference in prognostic parameters of T-LBL/ALL and B-LBL/ALL (P = 0.07). The difference in median survival time however was statistically significant (6.0 months +/- 1.1 months versus 15.0 months +/- 7.0 months).

CONCLUSIONSBoth TdT and CD99 are useful markers for the diagnosis of precursor lymphoblastic malignancy. T-LBL/ALL predominantly affects children or adolescent males and frequently presents with lymphadenopathy and mediastinal masses, whereas B-LBL/ALL are often accompanied by bone marrow and peripheral blood involvement. In general, T-LBL/ALL carries a poor prognosis. The prognostic criteria include age of older than 25 years and a classification of stage III or IV disease.

12E7 Antigen ; Adolescent ; Adult ; Age Factors ; Aged ; Antigens, CD ; metabolism ; Bone Marrow ; pathology ; Cell Adhesion Molecules ; metabolism ; Child ; Child, Preschool ; DNA Nucleotidylexotransferase ; metabolism ; Female ; Humans ; Immunophenotyping ; Male ; Middle Aged ; Neoplasm Staging ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; metabolism ; pathology ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; metabolism ; pathology ; Prognosis ; Retrospective Studies ; Survival Rate ; Young Adult

OBJECTIVETo clarify clinical and morphological features and immunophenotype of T lymphoblastic lymphoma/leukaemia (T-LBL/ALL) and to further improve the knowledge and diagnostic accuracy for T-ALL/LBL.

METHODS128 cases of T-LBL/ALL were analyzed for the clinical features, morphology, immunophenotype and TCR gene rearrangement using routine eosin and haematoxylin stain, immunohistochemistry and polymerase chain reaction combining with the clinical findings.

RESULTSIn 128 cases of T-LBL/ALL, there were 94 male and 34 female. The ratio of male/female was 2.8:1. The age of patients ranged from 4 to 88 years, with an average of 27 years and a median of 22 years. Lymph nodes and extranodal areas were involved in 58/128 and 27/128 cases of T-LBL/ALL, respectively. The other 43 cases had involvement of both nodal and extranodal areas. Cervical node and mediastinum were involved in 74 cases and 43 cases, respectively. Diffuse growth pattern of tumor cells was predominant. Nodular growth pattern was seen only in a few cases. Most cases composed of small to medium-sized lymphoblasts, and other 7 cases showed a composition of large lymphoblasts. Tumor cells expressed TdT in 121/128 (94.5%) cases, CD34 in 48/98 (49.0%) cases, CD3 in 78/108 (72.2%) cases, CD7 in 104/108 (96.3%) cases, CD43 in 56/63 (88.9%) cases, CD79a in 5/70 (7.1%) cases, CD10 in 25/76 (32.9%) cases, CD99 in 58/60 (96.7%) cases and Pax-5 in 4/91(4.4%) cases. All of the cases were negative for MPO. A follow up data, ranging from 1 to 53 months, was obtained in 51/128 (39.8%) patients. The over all survival rate was 68.6% and the median survival time was 12 months. Under a similar condition of carrying a positive staining result on CD3 in tumor cells, there was a statistically significant difference between patients in the group of over 30 of age and that with the age ranging from 11 to 30. Patients associating with a CD10 positive staining of tumor cells showed also a shorter survival period. In addition, there were 4 out of 5 cases showing the presence of TCR gene rearrangement.

CONCLUSIONST-LBL/ALL are aggressive in behavior, associating mainly with enlarged cervical lymph nodes and masses in the mediastinum, occurring predominantly in children and young adults. Although small to medium-sized tumor cells with diffuse pattern were found in most cases, however, large-sized tumor cells and nodular pattern could also be obtained in a few cases. Immunohistochemistry staining particularly adoption of CD7, Pax-5, TdT, CD34 and Ki-67 stainings in combination are helpful of making a diagnosis for T-LBL/ALL. Analysis of TCR gene rearrangement will be helpful for the diagnosis of a few difficult cases.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antigens, CD34 ; metabolism ; Antigens, CD7 ; metabolism ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; CD3 Complex ; metabolism ; Child ; Child, Preschool ; DNA Nucleotidylexotransferase ; metabolism ; Female ; Follow-Up Studies ; Gene Rearrangement, T-Lymphocyte ; Humans ; Ki-67 Antigen ; metabolism ; Lymphatic Metastasis ; Male ; Middle Aged ; Neprilysin ; metabolism ; PAX5 Transcription Factor ; metabolism ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; genetics ; metabolism ; pathology ; Survival Rate ; Young Adult