Rearrangement of the T cell receptor gamma-chain gene in childhood acute lymphoblastic leukemia

We analyzed rearrangements of the T cell receptor gamma-chain (T gamma) gene as well as rearrangements of the T cell receptor beta-chain (T beta) gene and immunoglobulin heavy-chain (IgH) gene in 68 children with acute lymphoblastic leukemia (ALL). All 15 patients with T cell ALL showed rearrangements of both T beta and T gamma genes. Twenty-four of 53 non-T, non-B ALL patients (45%) showed T gamma gene rearrangements and only 14 of these also showed T beta gene rearrangements. Only a single patient rearranged the T beta gene in the absence of T gamma gene rearrangement. The rearrangement patterns of the T gamma gene in non-T, non-B ALL were quite different from those observed in T cell ALL, as 20 of 23 patients retained at least one germline band of the T gamma gene. In contrast, all T cell ALL patients showed no retention of germline bands. These data indicate that rearrangement of the T gamma gene is not specific for T cell ALL. Further, the results also suggest that T gamma gene rearrangement precedes T beta gene rearrangement. The combined analysis of rearrangement patterns of IgH, T beta, and T gamma genes provides new criteria for defining the cellular origin of leukemic cells and for further delineation of leukemia cell heterogeneity.     

The Role of Serotonin (5-HT) in Behavioral Control: Findings from Animal Research and Clinical Implications

The neurotransmitters serotonin and dopamine both have a critical role in the underlying neurobiology of different behaviors. With focus on the interplay between dopamine and serotonin, it has been proposed that dopamine biases behavior towards habitual responding, and with serotonin offsetting this phenomenon and directing the balance toward more flexible, goal-directed responding. The present focus paper stands in close relationship to the publication by Worbe et al. (2015), which deals with the effects of acute tryptophan depletion, a neurodietary physiological method to decrease central nervous serotonin synthesis in humans for a short period of time, on the balance between hypothetical goal-directed and habitual systems. In that research, acute tryptophan depletion challenge administration and a following short-term reduction in central nervous serotonin synthesis were associated with a shift of behavioral performance towards habitual responding, providing further evidence that central nervous serotonin function modulates the balance between goal-directed and stimulus-response habitual systems of behavioral control. In the present focus paper, we discuss the findings by Worbe and colleagues in light of animal experiments as well as clinical implications and discuss potential future avenues for related research.     

Insulin receptors on leukemia and lymphoma cells

Tumor cells obtained from leukemia and lymphoma patients were investigated for specific insulin receptors. Using radioactive 125I- labeled insulin, specific insulin binding sites were demonstrated on most acute lymphocytic leukemia (ALL) and acute myelocytic leukemia (AML) cells, including acute promyelocytic leukemia (APL), chronic myelocytic leukemia (CML), and acute monocytic leukemia (AMoL) cells. Insulin receptors were not found on chronic lymphocytic leukemia (CLL) and malignant lymphoma (ML) cells. Specific insulin binding sites were also found on monocytes and thymocytes after treatment with phytohemagglutinin (PHA-P), but not on inactivated tonsil cells, peripheral blood lymphocytes, or thymocytes. There was no inverse correlation between the content of insulin receptors and the basal level of circulating insulin. These data suggest that the insulin receptor may be a new marker of acute leukemia and chronic myelocytic leukemia.     

The leftward deletion alpha-thal-2 haplotype in a black subject with hemoglobin SS

We have identified a black individual with homozygous sickle cell anemia who is the silent carrier of alpha-thalassemia (genotype - alpha/alpha alpha) due to heterozygosity for the leftward deletion alpha-thal-2 haplotype. This deletion has not been described previously in a black subject and is the only leftward deletion that we have found among 255 alpha-thal-2 chromosomes from sickle cell subjects. Its effects on the clinical, hematologic, biosynthetic, and cellular pathology of sickle cell anemia resemble those reported for the common alpha-thalassemia genotypes of the black population.     

Terminal differentiation surface antigens of myelomonocytic cells are expressed in human promyelocytic leukemia cells (HL60) treated with chemical inducers

The expression of two surface antigens present on the cell membrane of both human granulocytes and monocytes was studied during the process of myelomonocytic differentiation using two monoclonal antibodies (B9.8.1 and B13.4.1). These surface antigens are not present on immature myeloid cells nor on nonmyeloid hematopoietic cells, but can be detected when the cells are terminally differentiated. Among the bone marrow cells, B13.4.1 binds to metamyelocytes and B9.8.1 to metamyelocytes and a fraction (30%) of myelocytes. HL60 human promyelocytic leukemia cells did not react with such monoclonal antibodies. However, when such cells were induced to differentiate in vitro into mature myeloid elements by treatment with retinoic acid or dimethyl sulfoxide, 70%--90% of the differentiated cells expressed both surface antigens. Cell sorting studies on these treated HL60 cells indicated that myelocytes and metamyelocytes were the most immature cells expressing such markers. Expression of the two surface antigens was also observed when HL60 cells were induced to differentiate into monocyte/macrophage cells by treatment with the tumor promoter 12-O- tetradecanoyl-phorbol-13-acetate. Thus, human promyelocytic leukemia cells induced to differentiate in vitro by treatment with specific chemical agents express membrane antigens in the same pattern as normal bone marrow myeloid cells at the corresponding stage of differentiation.     

Eosinophils stimulate fibroblast DNA synthesis

Fibrosis complicates a number of chronic inflammatory diseases and occurs in some conditions following chronic hypereosinophilic syndromes. We assessed whether eosinophils might be a source of fibrogenic factors. Extracts of human and guinea pig cell populations enriched for eosinophils contained substances that stimulated tritiated thymidine incorporation by human fibroblasts. Supernatants derived from resting eosinophils and extracts prepared from eosinophil granules also contained fibrogenic factors. Our findings demonstrate a new potential role for eosinophils and suggest a causal relationship between tissue eosinophilia and scar formation in certain parasitic conditions.     

Establishing and managing a periodontal biobank for research: the sharing of experience

Periodontal bio‐repositories, which allow banking of clinically validated human data and biological samples, provide an opportunity to derive biomarkers for periodontal diagnosis, prognosis and therapeutic activities which are expected to improve patient management. This article presents the establishing of the Malaysian Periodontal Database and Biobank System (MPDBS) which was initiated in 2011 with the aim to facilitate periodontal research. Partnerships were established with collaborating centres. Policies on specimen access, authorship and acknowledgement policies were agreed upon by all participating centres before the initiation of the periodontal biobank. Ethical approval for the collection of samples and data were obtained from institutional ethics review boards. A broad‐based approach for informed consent was used, which covered areas related to quality of life impacts, genetics and molecular aspects of periodontal disease. Sample collection and processing was performed using a standardized protocol. Biobanking resources such as equipment and freezers were shared with the Malaysian Oral Cancer Database and Tissue Bank System (MOCDTBS). In the development of the MPDBS, challenges that were previously faced by the MOCDTBS were considered. Future challenges in terms of ethical and legal issues will be faced when international collaborations necessitate the transportation of specimens across borders.     

Prostate cancer detection upon transrectal ultrasound-guided biopsy in relation to digital rectal examination and prostate-specific antigen level: what to expect in the Chinese population?

We investigated the prostate cancer detection rates upon transrectal ultrasound (TRUS)-guided biopsy in relation to digital rectal examination (DRE) and prostate-specific antigen (PSA), and risk factors of prostate cancer detection in the Chinese population. Data from all consecutive Chinese men who underwent first TRUS-guided prostate biopsy from year 2000 to 2013 was retrieved from our database. The prostate cancer detection rates with reference to DRE finding and PSA level of < 4, 4–10, 10.1–20, 20.1–50 and > 50 ng ml⁻¹ were investigated. Multivariate logistic regression analyses were performed to investigate for potential risk factors of prostate cancer detection. A total of 2606 Chinese men were included. In patients with normal DRE, the cancer detection rates were 8.6%, 13.4%, 21.8%, 41.7% and 85.2% in patients with PSA < 4, 4–10, 10.1–20, 20.1–50 and > 50 ng ml⁻¹ respectively. In patients with abnormal DRE, the cancer detection rates were 12.4%, 30.2%, 52.7%, 80.6% and 96.4% in patients with PSA < 4, 4–10, 10.1–20, 20.1–50 and > 50 ng ml⁻¹ respectively. Older age, smaller prostate volume, larger number of biopsy cores, presence of abnormal DRE finding and higher PSA level were associated with increased risk of prostate cancer detection upon multivariate logistic regression analyses (P < 0.001). Chinese men appeared to have lower prostate cancer detection rates when compared to the Western population. Taking the different risk factors into account, an individualized approach to the decision of TRUS-guided biopsy can be adopted.