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.     

Detection of chymase activity using a specific peptide probe conjugated onto gold nanoparticles

Gold nanoparticles (AuNPs) can be applied in biosensors using fluorescence resonance energy transfer (FRET) technique. Based on this technique, we have established a sensitive and efficient biosensing method by modifying a peptide-probe onto AuNPs to detect proteinase enzyme activity in this study. This biosensing method was designed for chymase activity detection and applied in kidney disease diagnosis. In this study, 16 nm-AuNPs were used to construct the AuNPs-based fluorescence peptide probe (named AuNPs-peptide probe) for chymase activity determination. The peptide sequence is FITC-Acp-DRVYIHPFHLDDDDDC, which comprises a fluorophore at the N-terminal end, an enzyme (chymase) substrate (DRVYIHPFHL), a spacer (DDDDD) and cysteine (C) to conjugate to AuNPs surface. When the enzyme catalyzes the substrate sequence, the fluorophore drifts away from AuNPs and the fluorescence emitting signal can be excited at 495 nm and detected at 515 nm. The results indicate that the time required for the AuNPs-peptide probe for activity detection of chymase was only 15 min, and a linear correlation from 10 to 100 ng mL⁻¹ of chymase was acquired. The chymase reaction would be significantly inhibited by addition of specific chymase inhibitor chymostatin. The AuNPs-peptide probe was tested for the detection of high concentrations of trypsin and chymotrypsin, but only minor emitted fluorescence intensity was detected. According to these results, sensitivity and specificity of the AuNPs-peptide probe for chymase detection have been confirmed. AuNPs-peptide probe was successfully used for the detection of renal chymase activity; and the results indicate the pathogenically increased chymase activity in kidney tissue of nephropathic mice from aristolochic acid I treatment.

The gold nanoparticles (AuNPs) peptide probe functionalized with specific peptide sequences was developed for the sensitive and efficient detection of chymase activity.     

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.     

Disproportionate Reduction of Serotonin Transporter May Predict the Response and Adherence to Antidepressants in Patients with Major Depressive Disorder: A Positron Emission Tomography Study with 4-[18F]-ADAM

Background:

Many lines of evidence suggest the role of serotonin transporter (SERT)-mediated reuptake of serotonin in the pathophysiology and treatment of major depressive disorder (MDD). This study aimed to examine whether the pretreatment of SERT binding potential or SERT binding ratio between terminal projection regions relative to the midbrain raphe nuclei was associated with treatment outcomes to SERT-targeted antidepressants.

Methods:

We recruited 39 antidepressant-naïve patients with MDD and 39 heathy controls. Positron emission tomography with N,N-dimethyl-2-(2-amino-4-[¹⁸F]fluorophenylthio)benzylamine (4-[¹⁸F]-ADAM) was used to measure in vivo SERT availability prior to antidepressant treatment. The 21-item Hamilton Depression Rating Scale (HDRS) was use to assess the severity of depression from baseline to week 6. All the patients with MDD had HDRS scores of 18 or more.

Results:

Pretreatment SERT binding in the thalamus and striatum positively correlated with an early reduction in HDRS scores at week 3. Nonresponders and dropout patients showed a proportionate reduction in SERT binding in the terminal projection regions and midbrain compared to healthy controls. In contrast, a disproportionate reduction in SERT binding in the terminal projection regions relative to midbrain was observed in responders.

Conclusions:

The results of this study suggested that a disproportionate reduction in SERT binding between terminal projection regions and midbrain may predict better treatment outcomes in patients with MDD.     

Alterations of bone markers in obese patients with type 2 diabetes after bariatric surgery: A meta-analysis and systemic review of randomized controlled trials and cohorts

Background:The aim of this study is to evaluate the alterations in bone mineral density and other surrogate markers for osteoporosis in obese patients with type 2 diabetes mellitus (T2DM) who received Roux-en-Y gastric bypass (RYGB) versus medical treatment as control.Methods:We searched 4 electronic databases and reference lists of relevant studies for eligible research published before December, 2019. After quality assessment, eligible studies were synthesized for relevant outcomes, including lumbar spine bone mineral density (L-spine BMD) change, total hip BMD change, osteocalcin level, C-terminal telopeptide level, and parathyroid hormone level.Results:Three randomized clinical trials and 2 observational studies concerning 307 total obese T2DM patients were included. Follow-up ranged from 12 to 60 months. Patients underwent RYGB surgery were associated with both higher L-spine BMD loss (mean difference: −2.90, 95% CI: −2.99∼−2.81, P < .00001) and total hip BMD loss (mean difference: −5.81, 95% CI: −9.22∼−2.40, P = .0008). As to biochemical markers of bone metabolism, we found significantly higher osteocalcin level in medical treatment (control) group compared with RYGB group (mean difference: 11.16, 95% CI: 8.57–13.75, P < .00001). However, higher C-terminal telopeptide level and parathyroid hormone level were noted in medical treatment group (control) compared with RYGB group (mean difference: 0.29, 95% CI: 0.11–0.48, P = .002; mean difference: 1.56, 95% CI: 0.84–2.27, P < .0001).Conclusions:RYGB surgery is associated with negative impact on bone metabolism and increase the risk of osteoporosis in obese patients with T2DM. We suggest that clinicians acknowledge the adverse effects of surgery and keep monitoring bone mineral components in post-RYGB populations. Further studies regarding the optimal amount of perioperative and postsurgical supplementation should be evaluated.     

Altered controls of proliferation in proximal small intestine of the senescent rat.

The proximal small intestine responds to starvation by rapidly reducing crypt cell proliferation rate and villus cellularity and to resumption of food intake (refeeding) by abruptly increasing proliferation and the number of villus epithelial cells. We show that villus cellularity responds to starvation and refeeding similarly in young and aging animals. However, as compared to young animals, senescent rats showed increased basal DNA synthetic activity, starvation resulted in a smaller decrease in DNA labeling of crypt cells, and refeeding produced an abrupt broadening of the proliferative zone in older animals without concomitant increased numbers of villus cells. Such altered crypt proliferative responses resemble precancerous changes seen in the colon and the aberrant proliferation found in both small and large intestine after administration of the carcinogen dimethylhydrazine.     

Preoperative staging of gastric cancer by endoscopic ultrasound: the prognostic usefulness of ascites detected by endoscopic ultrasound

BACKGROUND: Endoscopic ultrasound (EUS) is the standard modality in local preoperative staging of gastric cancers and is reputedly able to detect ascites. However, the association between ascites detected by EUS and local tumor staging, peritoneal carcinomatosis, or survival after surgery is not well documented. GOALS: To assess the accuracy, sensitivity, and specificity of EUS in the preoperative staging and detection of ascites in gastric cancers. We also try to correlate ascites with histologic staging, tumor differentiation, and survival rate of gastric carcinoma after surgery. STUDY: The retrospective analysis was made in 57 consecutive patients with histologically confirmed gastric adenocarcinomas that underwent EUS before surgery. The accuracy of EUS was compared with the final surgical-pathologic findings. We estimated the prognostic usefulness by analyzing the clinicopathologic features of gastric adenocarcinomas and following up their survival rates. RESULTS: The overall T staging was 88% accurate by EUS. The accuracy for T staging was as follows: T1, 100%; T2, 33%; T3, 93%; and T4, 100%. About 50% of T2 cases were overstaged. The overall accuracy, sensitivity, and specificity of detecting lymph node metastasis by EUS were 79%, 79%, and 80%, respectively. One of the seven T1 cancers had regional lymph node metastasis, and it was missed by EUS, although the T classification was precisely staged based on finding submucosal invasion. A total of 22 patients (39%) had ascites detected by EUS; both the sensitivity and specificity of EUS in demonstrating ascites were 100% in our study. Ascites was significantly correlated with the depth of tumor invasion ( = 0.036), lymph node metastasis ( = 0.008), and poor cellular differentiation ( = 0.007), but it was not significantly correlated with macroscopic peritoneal carcinomatosis. The survival rate after surgical treatment was poor in those with gastric cancers with lymph node metastasis, ascites, or poorly differentiated tumors ( < 0.05). However, multivariate analysis showed that lymph node metastasis was the only significant prognostic predictor ( = 0.004). CONCLUSIONS: Endoscopic ultrasound is a valuable diagnostic tool in the local staging of gastric cancers and demonstration of ascites. Although the surgical treatment of gastric cancers with lymph node metastasis, ascites, or poor differentiation had poorer survival rate, only lymph node metastasis was proved to be a significant prognostic predictor in multivariate analysis.     

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.     

Integrated phytoremediation focused on microbial investigation

Phytoremediation is an environmentally friendly green rehabilitation technology that is often incorporated with an application to improve phytohormones required for the growth of agricultural plants with the expectation to improve the effectiveness of plant rehabilitation. This study adopts phytoremediation, a green remediation technology, for the sake of restoring soil fertility and ensuring environmental sustainability, and adds ethylenediaminedisuccinic acid (EDDS) and the plant growth regulator (GA₃) to examine the overall efficiency of phytoremediation. The experiments using pots in this study finds that environmentally sustainable phytoremediation achieves the greatest efficacy regarding the remediation of soil polluted by copper, zinc and nickel. The best combination of operational factors is the addition of the EDDS and GA₃. The environment where the EDDS is added shows a poorer performance in the remediation of the heavy metal lead. In addition, the PCR(Polymerase chain reaction)-DGGE analysis results of bacterial flora change show that the combination “heavy metal + EDDS + GA₃” brings about the richest bacterial flora, indicating that the addition of EDDS and GA₃ can stimulate microbial growth, thereby achieving richer bacterial flora.

Phytoremediation is a green rehabilitation technology that is often incorporated with an application to improve phytohormones required for the growth of agricultural plants with the expectation to improve the effectiveness of plant rehabilitation.