Acta Medica Nagasakiensia Vol. 60(2015) No. 2
ACTA MEDICA NAGASAKIENSIA

Serum Lactate Dehydrogenase (LDH) activity and soluble IL-2 Receptor-alpha (sIL-2R) levels are monitored as a marker of disease activity in patients with lymphoma. Although adult T-cell leukemia (ATL) cells are well known to release large amounts of sIL-2R,it remains unclear to what extent B-cell lymphoma cells shed sIL-2R in sera. Subtypes of mature B-cell lymphoma, including CD25⁺ hairy leukemic cells, were examined for the characteristics of sIL-2R levels in each subtype. In normal controls, the serum sIL-2R mean value was 260u/mL.The median serum sIL-2R value for 64 B-cell lymphoma cases was 506 u/mL;by subtype the median values were as follows: 1157 u/mL for 7 cases of chronic lymphocytic leukemia/hairy cell leukemia (CLL/HCL), 451 u/mL for 38 cases of diffuse large B-cell lymphoma (DLBCL), and 456 u/mL for 19 cases of follicular Lymphoma (FL). The median values of serum LDH activity by the above subtypes were 175 IU/mL, 204 IU/mL, and 198 IU/mL, respectively. There was distinct inter-subtype and inter-patient variation of serum sIL-2R.In particular, inter-case variation could be grouped into value for three concentration ranges: less than 300 u/mL, 300-1000 u/mL, and greater than 1000 u/mL. Cases with serum sIL-2R values of 1000 u/mL or more tended to have an especially high sIL-2R to LDH ratio, suggesting a close relationship between high sIL-2R and CD25-expressing lymphoma cells. With respect to sIL-2R and LDH levels, CLL/HCL, DLBCL, and FL showed similar distributions. Moreover, for sIL-2R levels exceeding 1000u/mL, sIL-2R levels were randomly high according to the LDH status. Conclusively, the combination of serum sIL-2R level and LDH activity can provide a better understanding of characteristics of subtypes of mature B-Cell Lymphoma and can be used as a reliable surrogate marker for evaluating numerical and biological data.

Objective Cisplatin is well known for producing severe adverse events, including renal dysfunction. To prevent renal dysfunction caused by cisplatin, routine magnesium supplementation is recommended. However, few reports exist about the efficacy of magnesium in preventing renal dysfunction. Therefore, the purpose of this study was to retrospectively survey the efficacy of magnesium in preventing renal dysfunction after administration of cisplatin. Methods We evaluated patients who received first-line cisplatin-based chemotherapy from May 2008 to June 2013. Results Data from 146 patients and a total of 394 treatments was analyzed. Elevation of serum creatinine was detected in 77 / 394 treatments (19.5%). Statistical significance was found between prevention of elevation of serum creatinine and magnesium supplementation. The other significant parameters were serum creatinine and eGFR levels before treatment and patient age. In multivariate analysis, magnesium and eGFR before treatment were statistically significant. Conclusions The study results suggest that magnesium supplementation might reduce nephrotoxicity caused by cisplatin. The eGFR level before treatment might be an important factor associated with nephrotoxicity after cisplatin administration.

Attachment between mothers and infants is the most primitive and primary form of human social relationship. Recently, it has been reported that the anterior prefrontal cortex (APFC) of infants younger than 3 years old may play an important function in forming attachments to their mothers. However, little is known about how the neural correlates of attachment develop after 3 years of age. Bowlby argued that there is a critical period, between birth and 2.5 years (0–30 months), for attachments to form and if it does not form in this time then it is not possible to develop thereafter. The current study investigated the role of the APFC in the attachment of 5 year olds to their mothers. Subjects included 18 young children (5.0 ± 0.4 years), whose mothers’ smiles were video recorded. By means of near-infrared spectroscopy (NIRS), we measured APFC activation in the children while viewing their mother smiling, and compared the activation with that resulting from an unfamiliar mother smiling. We found significant increases in right APFC activation in these 5 year olds in response to their mother’s smile. Furthermore, the APFC response to mothers’ smiles did not change as a function of age between 4 and 5 years old. These results suggest that the right APFC is still involved in young childrens’ attachment to their mothers until at least 5 years of age.

The aim of this study was to identify traumatic dental events that are related to post-traumatic stress disorder (PTSD) symptoms. At a dental clinic, first-time visitors were given a questionnaire that asked patients to indicate whether they felt fear in different dental situations. Patients’ dental anxiety was assessed using the short version of the Dental Anxiety Inventory (S-DAI). Patients’ trauma from dental treatments was assessed using the Impact of Event Scale-Revised (IES-R). Scores indicated that 16.5% of patients suffered from PTSD symptoms. A weak positive correlation was observed between S-DAI scores and IES-R scores. In a logistic regression analysis, “Not being able to get an anesthetic injection despite reporting pain during treatment” had independent effects on the PTSD symptom group. Our results suggest that a past experience with a dentist who denied a patient’s appeal for additional local anesthesia is related to the patient’s PTSD symptoms about dental treatment.

Background: Anxiety disorders are mental disorders that cause somatic symptoms for which patients may seek care from general medicine departments. We focused on anxiety disorders in middle-aged patients and examined the effect of a psychotherapeutic intervention. Materials and Methods: The participants were 14 middle-aged patients diagnosed with an anxiety disorder. Patients received pretreatment assessments and were randomly assigned to a pharmacotherapy group (n = 8) or a pharmacotherapy and psychotherapy group (n = 6). The duration of the study was three months. Pre-and post-treatment, the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), State-Trait Anxiety Inventory (STAI), and a visual analog scale (VAS) were administered. In the pharmacotherapy and psychotherapy group, salivary cortisol was collected pre- and post-psychotherapy at the first and final psychotherapy sessions. Result: Four patients in the pharmacotherapy group withdrew from the study. There were no significant differences in the total scores of the SF-36 or STAI between groups. Improvement was seen in the pharmacotherapy and psychotherapy group pre- and post- treatment. SF-36 subscales of bodily pain (p = 0.02) and mental health (p = 0.04) were significantly higher than posttreatment. The state anxiety score on the STAI improved post-treatment (p = 0.03). On the VAS, the pharmacotherapy and psychotherapy group’s symptoms were significantly improved (p = 0.02). Conclusion: This suggests that psychotherapy for middle-aged individuals contributes to the improvement of anxiety states and HRQoL in general medicine departments. It promotes the recognition of curative effects and prevents doctor shopping.

Background:　When multipass transmembrane molecules are located on the cell surface, there may be interaction with not only bioactive molecules but also pathogenic molecules in areas protruding outside the cell. In antibody-mediated autoimmune disorders, it has been found that the autoantibodies occasionally attack membrane molecules on the cell surface, thus causing the disease such as myasthenia gravis. In such cases, highly sensitive autoantibody detection technology is required for early diagnosis. However, autoantibody analysis technology that is specialized for membrane molecules is still under development. Here we demonstrate a novel method for detecting of antibodies against the extracellular portions of multipass transmembrane molecules. Methods:　Antibodies for muscarinic acetylcholine receptor type3 (M3R) were detected with two kinds of luciferase immunoprecipitaion systems (LIPS), conventional LIPS (cLIPS) and its modified application, termed modified LIPS (mLIPS). In mLIPS, antibodies against extracellular portions of membrane molecules could be preferentially detected. Results:　An antibody to the amino-terminal portion of human M3R was detected with modified LIPS with a high sensitivity. In contrast, an antibody to the carboxyl-terminal portion was not detected with mLIPS, because it did not interact with intracellular portions of M3R in living cells. We also found antibodies for M3R in a patient serum with Sjögren’s syndrome. Conclusion:　Our technology has a promising future, and we hope that it will be applied in the analysis of antibodies against a diverse range of multipass transmembrane molecules, including GPCRs.

　The toll-like receptor 4 (TLR4)-mediated immune response is considered as one of the triggers of acute respiratory distress syndrome. The agonistic monoclonal antibody UT12 specific for the TLR4/MD2 complex induces immune activation in a manner distinct from lipopolysaccharide (LPS). In order to compare the effects of this differential TLR4 signaling activation, we examined immune cell recruitment to the lung following intratracheal inoculation with UT12 and LPS in mice. The increase in pulmonary neutrophils was much higher after LPS treatment compared with UT12 treatment, while CD11b^hiCD11^＋cells increased to similar levels following both treatments. These changes were MyD88-dependent and TRIF-independent. These differential effects on immune cell recruitment to the lung suggest distinct underlying mechanisms in response to TLR4 stimulation. These findings further indicate that TLR signaling can lead to different outcomes depending on the ligand and activation pathway, which may relate to the complex pathogenesis of inflammatory lung diseases.