Synergistic effect of thyroid hormone and thyrotropin on iodothyronine 5'-deiodinase in FRTL-5 rat thyroid cells

The effects of T3 and T4 on the iodothyronine 5'-deiodinase (5'-D) activity in FRTL-5 rat thyroid cells were investigated. T3 and T4 stimulated the 5'-D activity in a dose-dependent manner. Kinetic studies showed that the stimulation of the 5'-D by T3 was associated with an increase in maximum velocity (Vmax) in [11.9 +/- 0.2 (mean +/- SE) and 25.4 +/- 0.9 pmol I-released/mg protein.min, respectively, in control and cultured with 10(-9) M T3 for four days] but without a change in apparent Michaelis-Menten constant (Km) (94.8 +/- 5.3 nM and 105.4 +/- 12.1 nM, respectively). Furthermore, cycloheximide (5 microM) completely abolished the stimulatory effect of T3 on the 5'-D activity. T3 and T4 also enhanced the 5'-D activity stimulated by TSH in a dose-dependent manner. Kinetic studies showed that the stimulatory effect of T3 on the 5'-D stimulated by TSH was again associated with an increase in Vmax (86.0 +/- 4.0 and 166.5 +/- 1.9 pmol I- released/mg protein.min, respectively, cultured with 0.3 U/liter TSH and cultured with TSH plus 10(-9) M T3 for four days) without a change in apparent Km (114.0 +/- 7.4 nM and 111.6 +/- 12.5 nM, respectively). Cycloheximide (5 microM) completely abolished the stimulatory effect of TSH plus T3 on the 5'-D activity. There were no significant differences observed between cells cultured with TSH and with TSH plus T3 in either the intra- or extracellular cAMP contents. Furthermore, T3 enhanced the 5'-D activity stimulated by (Bu)2 cAMP. These results strongly suggest that T3 or T4 was synergistic with TSH in stimulating the 5'-D activity in FRTL-5 cells, and that cAMP production would be an important component of the synergism.     

Clinical characteristics and genetic analysis of childhood acute lymphoblastic leukemia with hemophagocytic lymphohistiocytosis: a Japanese retrospective study by the Kyushu–Yamaguchi Children’s Cancer Study Group

This present study sought to analyze acute lymphoblastic leukemia (ALL) patients with hemophagocytic lymphohistiocytosis (HLH) registered in Kyushu–Yamaguchi Children’s Cancer Study Group studies conducted between 1996 and 2007. Four of 357 patients, including two of 318 patients with B cell precursor acute lymphoblastic leukemia (BCP-ALL) and two of 39 of those with T cell acute lymphoblastic leukemia (T-ALL), were identified. HLH was observed more frequently in the T-ALL patients than in the BCP-ALL patients (P = 0.061). The mean age of 13.0 years at the diagnosis of leukemia in the HLH + ALL group was significantly higher than the 6.05 years observed in the remaining ALL groups (P = 0.001). A female predisposition was noted, as all four patients were female (P = 0.043). In two of four patients, the leukemic cells exhibited deletions on the long arm of chromosome 6 (P = 0.003). Three patients suffered from HLH during maintenance therapy. Parvovirus B19 infection and cytomegalovirus reactivation were identified as causes of HLH in one and two patients, respectively. All four patients are currently in complete remission, although one developed relapse of leukemia after receiving maintenance therapy. Based on the genetic analyses, non-synonymous single nucleotide polymorphisms (SNPs) in UNC13D, syntaxin 11, and STXBP2 were identified in all patients. Clinicians should therefore be aware of the risk of HLH during maintenance therapy, especially in older T-ALL patients with SNPs in familial HLH causative genes.     

Comparison of the value of tissue-sealing devices for thoracoscopic pulmonary lobectomy in small children: a first report

Accurate division and sealing of lung parenchyma particularly in cases of total or near total incomplete fissure are crucial for preventing air leakage following thoracoscopic pulmonary lobectomy (TPL). However, conventional endoscopic stapling devices cannot be used during TPL in small children because of limited space. Consequently, Ligasure (LS) and Enseal (ES) devices are being used instead. We are the first to compare LS and ES for efficacy and efficiency during TPL. Of 26 TPL (6 upper, 3 middle, and 17 lower) performed for congenital adenomatoid malformation (n = 16) and sequestration (n = 10), incomplete fissure was found in 14. TPL (LS = 11; ES = 15) was performed conventionally in the lateral decubitus position with single lung ventilation using four 5 mm trocars. All cases had a chest tube inserted intraoperatively that was left in situ. Patient demographics, location of pathology, incidence of incomplete fissure, mean age/weight at TPL, mean blood loss, and mean operative time were all similar. However, duration of chest tube insertion was significantly shorter in ES because there was less postoperative air leakage (1.3 vs. 3.9 days; p < 0.05). ES would appear to seal lung parenchyma more effectively during TPL based on the shorter duration of chest tube insertion.     

Risk factors for de novo hepatitis B during solid cancer treatment

BACKGROUNDReactivation of hepatitis B virus (HBV) during anticancer treatment is a critical issue. When treating patients with solid tumors, it is unclear whether specific cancer types or treatments affect HBV reactivation in hepatitis B surface antigen (HBsAg)-negative and hepatitis B core antibody (HBcAb)-positive patients, so-called de novo hepatitis B patients. The risk of de novo hepatitis B may vary based on different background factors.AIMTo determine the frequency and risk factors for de novo hepatitis B during solid tumor treatment.METHODSThis retrospective cohort study comprised 1040 patients without HBsAgs and with HBcAbs and/or hepatitis B surface antibodies (HBsAbs). The patients were treated for solid cancer from 2008 to 2018 at the National Kyushu Cancer Center and underwent HBV DNA measurements. Patient characteristics and disease and treatment information were investigated. HBV DNA measurements were performed using TaqMan polymerase chain reaction (PCR). To identify the risk factors associated with HBV DNA expression, the age, sex, original disease, pathology, treatment method, presence or absence of hepatitis C virus (HCV), and HBsAb and/or HBcAb titers of all subjects were investigated. In patients with HBV DNA, the time of appearance, presence of HBsAgs and HBsAbs at the time of appearance, and course of the subsequent fluctuations in virus levels were also investigated.RESULTSAmong the 1040 patients, 938 were HBcAb positive, and 102 were HBcAb negative and HBsAb positive. HBV DNA expression was observed before the onset of treatment in nine patients (0.9%) and after treatment in 35 patients (3.7%), all of whom were HBcAb positive. The HBV reactivation group showed significantly higher median HBcAb values [9.00 (8.12-9.89) vs 7.22 (7.02-7.43), P = 0.0001] and significantly lower HBsAb values (14 vs 46, P = 0.0342) than the group without reactivation. Notably, the reactivated group showed a significantly higher proportion of cancers in organs related to digestion and absorption (79.0% vs 58.7%, P = 0.0051). A high HBcAb titer and cancers in organs involved in digestion and absorption were identified as independent factors for HBV reactivation (multivariate analysis, P = 0.0002 and P = 0.0095). The group without HBsAbs tended to have a shorter time to reactivation (day 43 vs day 193), and the frequency of reactivation within 6 mo was significantly higher in this group (P = 0.0459) than in the other group.CONCLUSIONA high HBcAb titer and cancers in organs involved in digestion and absorption are independent factors that contribute to HBV reactivation during solid tumor treatment.     

Positive association between a DNA sequence variant in the serotonin 2A receptor gene and schizophrenia

Sixty-two patients with schizophrenia and 96 normal controls were investigated for genetic association with restriction fragment length polymorphisms (RFLPs) in the serotonin receptor genes. A positive association between the serotonin 2A receptor gene (HTR2A) and schizophrenia was found, but not between schizophrenia and the serotonin 1A receptor gene. The positive association we report here would suggest that the DNA region with susceptibility to schizophrenia lies in the HTR2A on the long arm of chromosome 13. © 1996 Wiley-Liss, Inc.     

Three-Dimensional Nanoscale Morphological Surface Analysis of Polymeric Particles Containing Allium sativum Essential Oil

Biodegradable particles were developed using poly-ε-caprolactone and gelatin carriers containing different concentrations of Allium sativum essential oil (EO) (360 µg/mL, 420 µg/mL, and 460 µg/mL). Atomic force microscopy was useful to evaluate the particles’ surface based on morphological parameters. The particles’ size varied from 150 nm to 300 nm. The diameter was related to the increase of the particles’ height as a function of the EO concentration, influencing the roughness of the surface core values (from 20 to 30 nm) and surface irregularity. The spatial parameters Str (texture aspect ratio) and Std (texture direction) revealed low spatial frequency components. The hybrid parameters Sdq (root mean square gradient) and Sdr (interfacial area ratio) also increased as a function of the EO concentration, revealing fewer flat particles. On the other hand, the functional parameters (inverse areal material ratio and peak extreme height) suggested differences in surface irregularities. Higher concentrations of EO resulted in greater microtexture asperity on the particles’ surface, as well as sharper peaks. The nanoscale morphological surface analysis allowed the determination of the most appropriate concentration of encapsulated EO, influencing statistical surface parameters.     

Effect of exercise on ventricular diastolic time in coronary artery disease

To evaluate diastolic time during uninterrupted upright exercise, 28 normal volunteers (group 1) and 12 men with coronary artery disease (group 2) were studied by ear densitography. Electromechanical systole-heart rate and diastolic time-heart rate regression equations during upright exercise were obtained from group 1. Electromechanical systole-heart rate had an inverse linear relation (electromechanical systole = 480 - 1.4 heart rate) and diastolic time-heart rate had an inverse nonlinear relation (diastolic time = 1206e-0.02 heart rate). Although there were no significant differences in electromechanical systole and diastolic time at 1 minute of exercise between patients with and without CAD, at peak exercise prolongation of electromechanical systole and consequent shortening of diastolic time in patients with CAD were observed. This disproportionate shortening of diastole with lengthening of systole at peak exercise tends to decrease myocardial perfusion and, hence, oxygen supply, while increasing myocardial oxygen demand, contributing to aggravation of ischemia in patients with CAD.     

Colonic Lymphoid Follicle Hyperplasia after Gastrectomy in Rats

Nodular lymphoid hyperplasia (NLH) of the human colon has been associated with multiple diseases and symptoms. Causes include food allergies, infections, inflammatory bowel disease, and immunodeficiency, and gastrectomy is not usually considered to be the etiology. Nine rats two weeks after total gastrectomy and 12 control rats were sacrificed and submitted for histological examination. In the gastrectomy group, we found lymphoid hyperplasia throughout the entire colon mucosa. The cross-sectional area of lymphoid follicles was increased to be five-fold larger than that in the rats in the control group (sham surgery). Lymphoid follicles were classified into primary and secondary follicles according to the presence/absence of germinal centers; the gastrectomy group had a significantly larger number of secondary follicles. When T cell and B cell classification of lymphocytes was performed, there was no difference between gastrectomy and control groups at T:B = 40:60. When the lymphoid follicles were classified, the proportion of T lymphocytes increased in the secondary follicle (T:B = 40:60) compared with in the primary follicle (T:B = 20:80). Gastrectomy significantly activated lymphocytic intestinal immunity by altering the intestinal environment, causing colonic NLH. Gastrectomy in rats is a good animal model for the study of NLH in colorectal diseases.     

Treatment of lateral node metastasis from lower rectal cancer

Lateral lymphatics of the rectum originate in the area where branches of the inferior hypogastric plexus and the middle rectal vessels from the internal iliac vessels enter the mesorectum below the level of the peritoneal reflection in the pelvis, then reach the bifurcation of iliac vessels along the internal iliac vessels. Among lateral lymph nodes, the middle rectal, obturator, and internal iliac lymph nodes are important from the viewpoint of both the incidence of metastais and treatment effects. Although total mesorectal excision (TME) had become the standard surgical treatment for rectal cancer by the 1990s, this technique does not treat lateral node metastasis. A randomized clinical trial of TME versus D3 lymphadenectomy (JCOG0212) was started in 2003, and the registration of 701 patients with lower rectal cancer was completed in August 2010. The results of this clinical trial are highly anticipated. In Japan, where the rate of local recurrence after surgery is low, patients at high risk of local recurrence such as those with lateral node metastasis, T4 disease, and multiple lymph node metastases in the mesorectum should be selected to receive preoperative chemoradiation. Japanese surgeons who treat rectal cancers are in an advantageous position because they have the additional measure of lateral node dissection along with TME and chemoradiotherapy.