Partial thyroxine-binding globulin deficiency in a family with coding region mutations in the TBG gene.

PURPOSE: T4-binding globulin (TBG) is the main thyroid hormone (TH) transporter present in human serum. Inherited thyroxine-binding globulin (TBG) deficiency is caused by mutations in the TBG (SERPINA7) gene, which is located on the X chromosome. This study was performed to report and evaluate coding region mutations in TBG gene for partial thyroxine-binding globulin deficiency. METHODS: A pedigree spanning four generations is described in this study. The proband is a female with partial TBG deficiency. All members of this pedigree underwent thyroid function tests, while Sanger sequencing was used to identify the TBG gene mutations. Bioinformatics databases were used to evaluate the deleterious effects of the mutation(s). Two hundred and seven unrelated individuals were used to evaluate the thyroid function of individuals with different TBG mutations. A one-way ANOVA was used to analyze the impact of the TBG mutations on thyroid function. RESULTS: TBG gene sequencing results revealed that the proband had a novel mutation in codon 27 leading to alanine to valine substitution (p.A27V). This mutation was associated with lower serum T4 levels (p < 0.0001) when compared to the groups that did not carry the mutation. The previously reported p.L283F mutation was also found in the proband. The hemizygous p.L283F individuals presenting with lower T4 serum and TBG levels (p < 0.001) when compared to wildtype males and females. Both mutations were deleterious upon SIFT and PolyPhen-2 evaluation. CONCLUSION: Associated with partial thyroxine-binding globulin deficiency, this study reports a novel p.A27V mutation in the TBG gene.

Anti-tumor effect of endostatin in a sleep-apnea mouse model with tumor.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with cancer incidence and mortality. The underlying mechanism is unclear. This study aims to evaluate the influence of intermittent hypoxia (IH), a novel hallmark of OSA, on tumor and to access the anti-tumor effect of endostatin on a mouse model with OSA. METHODS: The C57BL/6 J mice were randomly classified into four groups: control (normoxia) (CTL), control plus endostatin (CTL + ED), IH, and IH plus endostatin (IH + ED). Mice in IH and IH + ED groups were subjected to IH 8 h per day in 5 weeks. Lewis lung cancer cells were injected into the flank of each mouse after 1 week of IH exposure. Endostatin was also intraperitoneally injected after tumor volume reached about 200 mm3. The maximum standard uptake values (SUVmax) were detected by micro-positron emission tomography-computed tomography (micro-PET-CT) imaging prior and post-endostatin administration. Microvessel density (MVD) and vascular endothelial growth factor (VEGF) were determined for evaluating the anti-tumor effect of endostatin among the normoxia and IH conditions. RESULTS: Mice had higher SUVmax in the IH group than the CTL group (p < 0.01). When compared with mice in the CTL group, those in the IH group had significantly greater MVD values (p < 0.001). The SUVmax can be attenuated by endostatin both in the CTL (p < 0.01) and IH conditions (p < 0.001). When compared with CTL group, mice in the IH group had increased MVD values (p < 0.001) and VEGF expression both at mRNA (p < 0.05) and protein levels (p < 0.001 in western blotting results). Treatment with endostatin attenuated serum and tissue VEGF levels, lowering the MVD values. As compared to normoxia condition, the endostatin-therapeutic effects were more significant under the IH condition (p < 0.05 in western blotting results). CONCLUSIONS: Micro-PET-CT imaging is a promising non-invasive technique to evaluate the tumor metabolic characteristics under IH condition in vivo. The anti-tumor effect of endostatin under IH condition is superior to that of the normoxia condition.

Contrast-enhanced ultrasound of intrahepatic cholangiocarcinoma: correlation with pathological examination.

OBJECTIVE: To investigate the correlation between enhancement patterns of intrahepatic cholangiocarcinoma (ICC) on contrast-enhanced ultrasound (CEUS) and pathological findings. METHODS: The CEUS enhancement patterns of 40 pathologically proven ICC lesions were retrospectively analysed. Pathologically, the degree of tumour cell and fibrosis distribution in the lesion was semi-quantitatively evaluated. RESULTS: 4 enhancement patterns were observed in the arterial phase for 32 mass-forming ICCs: peripheral rim-like hyperenhancement (n=19); heterogeneous hyperenhancement (n=6); homogeneous hyperenhancement (n=3); and heterogeneous hypo-enhancement (n=4). Among the four enhancement patterns, the differences in tumour cell distribution were statistically significant (p<0.05). The hyperenhancing area on CEUS corresponded to more tumour cells for mass-forming ICCs. Heterogeneous hyperenhancement (n=2) and heterogeneous hypo-enhancement (n=2) were observed in the arterial phase for four periductal infiltrating ICCs. In this subtype, fibrosis was more commonly found in the lesions. Heterogeneous hyperenhancement (n=1) and homogeneous hyperenhancement (n=3) were observed in the arterial phase for four intraductal growing ICCs. This subtype tended to have abundant tumour cells. CONCLUSION: The CEUS findings of ICC relate to the degree of carcinoma cell proliferation at pathological examination. Hyperenhancing areas in the tumour always indicated increased density of cancer cells.

Analysis of thrombin-antithrombin complex contents in plasma and hematoma fluid of hypertensive intracerebral hemorrhage patients after clot removal.

BACKGROUND AND PURPOSE: Animal experiments indicate that the cerebral thrombin is associated with secondary brain damage after intracerebral hemorrhage (ICH). This study was aimed to investigate the concentrations of thrombin-antithrombin complex (TAT) in hematoma fluid and plasma of the patients with ICH after surgery and analyze the correlation between TAT complex levels and severity of ICH. METHODS: Sixty patients with ICH were enrolled. Craniotomy for removal of intracranial blood clot was performed within 24h after ICH. Hematoma fluid and plasma were collected on postoperative days 1, 2, and 4. The plasma obtained from healthy subjects and cerebrospinal fluid from patients without cerebrovascular diseases served as controls, respectively. Enzyme-linked immunosorbent assay was used to determine the concentrations of TAT complex in the patients and controls. RESULTS: TAT complex concentrations in both postoperative plasma and hematoma fluid of patients with ICH were significantly higher than those of the controls (P<0.01). In patients with ICH, hematoma fluid had a higher TAT complex level than plasma (P<0.01). The preoperative hemorrhage volume and postoperative TAT complex levels in plasma and hematoma fluid correlated positively with National Institutes of Health stroke scale and negatively with Glasgow coma score (P<0.01). CONCLUSION: This study indicates that TAT complex levels of plasma and hematoma fluid correlate positively with the severity of ICH. Determination of the plasma TAT complex concentration is helpful for the evaluation of the severity of post-ICH brain injury.

Imaging features of hepatic angiomyolipomas on real-time contrast-enhanced ultrasound.

The aim of this study was to evaluate the imaging features of hepatic angiomyolipoma (AML) on contrast-enhanced ultrasound (CEUS). The imaging features of 12 pathologically proven hepatic AML lesions in 10 patients who had undergone baseline ultrasound (BUS) and CEUS examinations were evaluated retrospectively. The enhancement extent, pattern and dynamic change, along with the enhancement process, on CEUS were analysed. The diagnostic results of BUS and CEUS before pathological examination were also recorded. The results showed that 75% (9/12) of the AML lesions exhibited mixed echogenicity on BUS and most showed remarkable hyperechogenicity in combination with a hypoechoic or anechoic portion. Arterial flow signals were detected in 75% (9/12) of the lesions on colour Doppler imaging. On CEUS, 66.7% (n = 8) of the 12 lesions exhibited hyperenhancement in the arterial phase, slight hyperenhancement (n = 2) or isoenhancement (n = 6) in the portal phase, and slight hyperenhancement (n = 1) or isoenhancement (n = 7) in the late phase. Three (25%) lesions exhibited hyperenhancement in the arterial phase and hypoenhancement in both portal and late phases. One (8.3%) lesion exhibited hypoenhancement throughout the CEUS process. Before pathological examination with BUS, only 3 (25%) lesions were correctly diagnosed as hepatic AML. Conversely, on CEUS, correct diagnoses were made for 66.8% (8/12) of hepatic AMLs. Therefore, arterial hyperenhancement and subsequent sustained enhancement on CEUS were found in the majority of hepatic AMLs. The combination of BUS and CEUS leads to the correct diagnosis in the majority of hepatic AMLs, and is higher than the success rate achieved by BUS alone.

Enhancement patterns of intrahepatic cholangiocarcinoma: comparison between contrast-enhanced ultrasound and contrast-enhanced CT.

The aim of this study was to compare the enhancement pattern of intrahepatic cholangiocarcinoma (ICC) on contrast-enhanced ultrasound (CEUS) with that on contrast-enhanced computed tomography (CECT). 40 pathologically proven ICC lesions in 40 patients were evaluated retrospectively with both CEUS and CECT. The enhancement level and pattern in the dynamic phases on both CEUS and CECT were analysed. The diagnostic results of CEUS and CECT before pathological examination were also recorded. During arterial phases, the number of lesions that appeared as (i) peripheral irregular rim-like hyperenhancement, (ii) diffuse heterogeneous hyperenhancement, (iii) diffuse homogeneous hyperenhancement and (iv) diffuse heterogeneous hypoenhancement were 19 (47.5%), 9 (22.5%), 5 (12.5%) and 7 (17.5%), respectively, on CEUS, and 22 (55.0%), 3 (7.5%), 2 (5.0%) and 13 (32.5%), respectively, on CECT (p = 0.125). In the portal phase, the number of lesions showing hyperenhancement and hypoenhancement were 1 (2.5%) and 39 (97.5%), respectively, on CEUS, and 15 (37.5%) and 25 (62.5%) on CECT (p = 0.0001). CEUS made a correct diagnosis in 32 (80.0%) lesions before pathological examination; CECT made a correct diagnosis in 27 (67.5%) lesions (p = 0.18). In conclusion, the enhancement patterns of ICC on CEUS were consistent with those on CECT in the arterial phase, whereas in the portal phase ICC faded out more obviously on CEUS than on CECT. CEUS had the same accuracy as CECT in diagnosing ICCs, and so can be used as a new modality for the characterization of ICC.