Integrin α11 in non–small cell lung cancer is associated with tumor progression and postoperative recurrence

Integrins are transmembrane proteins that mediate cell adhesion to the extracellular matrix. Integrin α11 (ITGA11) is not expressed in normal alveolar epithelial cells and is a known receptor for collagen. While integrin α11β1 overexpression in the tumor stroma has been associated with tumor growth and metastatic potential of non–small cell lung cancer (NSCLC), little is known about the role of ITGA11 in tumor cells. Thus, we examined the RNA expression of ITGA11 by quantitative RT‐PCR in 80 samples collected from NSCLC patients who had undergone surgical resection and analyzed the clinical outcomes. We found that high expression of ITGA11 was associated with lower recurrence‐free survival in all NSCLC patients (P = 0.043) and in stage I NSCLC patients (P = 0.049). These results were consistent with in silico analyses of the Cancer Genome Atlas database. We also analyzed cell proliferation, migration and invasion capacity in lung cancer cell lines after overexpression of ITGA11. Overexpression of ITGA11 in lung cancer cell lines had little effect on cell proliferation but resulted in increased migration and invasion capacity. Our findings suggest that ITGA11 plays a significant role in cancer migration and invasion, leading to higher recurrence. ITGA11 expression may be a predictor of poor prognosis in patients with surgically resected NSCLC.     

A case of immediate allergy to anisakis following saury intake]

We report here a 76-year-old male that presented with an immediate allergy to Anisakis following saury intake. Three and a half hours after eating pressed saury sushi, whole-body pomphus appeared including itching, facial dropsical swelling, and dyspnea. Diagnostic tests revealed specific IgE antibodies against anisakis simplex and a skin prick test was positive using an extraction of anisakis simplex. The results of skin prick tests using the body and internal organs of a saury were negative. Based on these results, we diagnosed the case as immediate allergy to Anisakis. Anisakis is parasitic to a diverse array of fish, and it seems rare that eating saury will induce an allergic response because the reported parasitic rate of Anisakis on saury is only 5%. In addition, as tropomyosin is currently considered to be the primary cause of allergies to Anisakis, renewed attention should be paid to other foods for which tropomyosin is also assumed to be a common antigen.     

Clinical features of patients with obsessive-compulsive disorder showing different pharmacological responses]

BACKGROUND: Although selective serotonin reuptake inhibitors (SSRIs) are the mainstay of pharmacological treatment for obsessive-compulsive disorder (OCD), some OCD patients do not show improvement. Sometimes, the addition of a low-dose atypical antipsychotic, such as risperidone, or olanzapine, to ongoing SSRI treatment has been shown to be effective. However, there are patients who still show no response after trials with this augmentation therapy. In the present study, we examined the clinical features of OCD patients who showed different responses to pharmacological treatment. SUBJECTS AND METHOD: Fifty OCD patients were divided into three groups according to their pharmacological responses: responders to SSRI (group A: n= 25), responders to SSRI with an atypical antipsychotic (group B: n= 15), and non-responders to both SSRI and SSRI with an atypical antipsychotic (group C: n= 10). We examined the clinical features such as age, sex, age of onset, duration of illness, types of obsessive-compulsive symptoms, severity, improvement after treatment, insight into disease, depression, comorbidity, involving family members in compulsive or ritualistic behavior, and the level of social adaptation of each OCD group. RESULTS: Twenty five patients showed a good response to SSRI monotherapy, 15 showed a response to antipsychotic augmentation, and 10 were non-responders to both SSRI and SSRI with an atypical antipsychotic. Significantly lower insight levels were observed only in group B and higher depressive levels in group C. OCD patients who were refractory to SSRI monotherapy showed comorbidity at a significantly higher frequency. OCD patients in group A showed significantly greater improvement, and group B showed inferior social adaptation after treatment. There were no significant differences in age, sex, age of onset, duration of illness, severity, involving family members in compulsive or ritualistic behavior, and social adaptation before treatment in the three OCD groups. CONCLUSION: There were differences in the clinical features of OCD patients who showed different responses to pharmacological treatment. Our results suggest that OCD is clinically and biologically heterogeneous. It may be important to divide OCD patients into subgroups for future studies.     

A case of aseptic meningitis caused by relapsing polychondritis]

We report a patient of relapsing polychondritis (RP) with antecedent aseptic meningitis. A 65-year-old man has developed headache and fever. Neurological examination showed meningeal signs, and cerebrospinal fluid (CSF) examination revealed meningeal inflammation which contained 450 polymorphonuclear cells/microl, 302 mononuclear cells/microl, and 0 red cells/microl, with 79 mg protein/dl. Serologic testing for autoimmune disease as well as the culture and cytology of CSF were negative. He admitted our hospital as having aseptic meningitis and experienced antibiotic therapy. However, his pyrexia continued and he developed repeating visual and hearing impairment reacting to steroid. Three months later, he became behaviorally deaf, and bilateral auricular chondritis occurred with nonerosive seronegative inflammatory polyarthritis. The result of condral biopsy was consistent with the diagnosis of RP showing cartilage surrounded by an intense inflammatory cell response with a decreased number of chondrocytes. A clinical diagnosis was made and prednisolone 60 mg/day was begun with the result of resolution of the auricular chondritis, and slight improvement of his deafness. Aseptic meningitis is a rare complication of RP. Only one report detailed RP patient who had preceding meningitis. RP is a potentially lethal disease resulting from suffocation by airway collapse, the complications of a cardiac large vessel, and so on. For improvement of a life prognosis, an early diagnosis and treatment are indispensable. Although RP is a rare discovery, it is necessary that RP should be taken into consideration and be differentiated as a cause of relapsing aseptic meningitis.     

Alterations in the glomerulus in aminonucleoside nephrosis in analbuminemic rats

Whether obliteration of glomerular epithelial foot processes and increases in urinary N-acetyl-beta-D-glucosaminidase (NAG) activity are the consequence or the cause of proteinuria after administrations of the aminonucleoside of puromycin was examined using Nagase analbuminemic rats. The administration of puromycin aminonucleoside to Nagase analbuminemic rats did not induce proteinuria. However, the increase in urinary NAG activity and the degree of abnormality of foot processes in the glomerular cells were similar to those in control Sprague-Dawley rats. These findings suggest that NAG excretion and the morphological alterations of epithelial cells in nephrosis are not the consequence of massive proteinuria.     

High susceptibility of analbuminemic rats to neurogenic tumor induction by transplacental administration of N-ethyl-N-nitrosourea.

The susceptibilities of Nagase analbuminemic rats (NAR) and control Sprague-Dawley rats (SDR) to N-ethyl-N-nitrosourea (ENU) were compared. In Experiment I, the rats were given daily subcutaneous injections of 10 mg/kg of ENU for a week from 4 weeks of age. In Experiment II, mother rats were given a single subcutaneous injection of 60 mg/kg of ENU on day 17 of pregnancy and tumor development in their offspring was examined. In Experiment I, the incidence of neurogenic tumors was slightly, but not significantly, higher in NAR than in control rats. In Experiment II, the incidence of total tumors including neurogenic tumors was significantly higher in NAR (40/43, 93.0%) than in SDR (13/61, 21.3%). NAR showed particularly high susceptibility to induction of neurogenic tumors (34/43, 79.1%) and renal tumors (15/43, 34.9%). In an attempt to elucidate the underlying mechanisms of the increased susceptibility of NAR to ENU, O6-ethylguanine, a major premutagenic ethylated DNA adduct, was quantitated in fetal brain DNA of NAR and SDR after a pulse exposure to 60 mg/kg ENU. No significant difference in the initial formation or subsequent repair of O6-ethylguanine was observed in the two strains, indicating that abnormality at some later stage(s) of chemical carcinogenesis may lead to the increased susceptibility of NAR to induction of neurogenic tumors.     

Effects of exposure to microwaves on cellular immunity and placental steroids in pregnant rats.

OBJECTIVES: Microwaves produce various detrimental changes based on actions of heat or non-specific stress, although the effects of microwaves on pregnant organisms has not been uniform. This study was designed to clarify the effect of exposure to microwaves during pregnancy on endocrine and immune functions. METHODS: Natural killer cell activity and natural killer cell subsets in the spleen were measured, as well as some endocrine indicators in blood--corticosterone and adrenocorticotrophic hormone (ACTH) as indices of the hypothalamic-pituitary-adrenal axis--beta-endorphin, oestradiol, and progesterone in six female virgin rats and six pregnant rats (nine to 11 days gestation) exposed to microwaves at 10 mW/cm2 incident power density at 2450 MHz for 90 minutes. The same measurements were performed in control rats (six virgin and six pregnant rats). RESULTS: Skin temperature in virgin and pregnant rats increased immediately after exposure to microwaves. Although splenic activity of natural killer cells and any of the subset populations identified by the monoclonal antibodies CD16 and CD57 did not differ in virgin rats with or without exposure to microwaves, pregnant rats exposed to microwaves showed a significant reduction of splenic activity of natural killer cells and CD16+CD57-. Although corticosterone and ACTH increased, and oestradiol decreased in exposed virgin and pregnant rats, microwaves produced significant increases in beta-endorphin and progesterone only in pregnant rats. CONCLUSIONS: Microwaves at the power of 10 mW/cm2 produced activation of the hypothalamic-pituitary-adrenal axis and increased oestradiol in both virgin and pregnant rats, suggesting that microwaves greatly stress pregnant organisms. These findings in pregnant rats suggest that--with exposure to microwaves--pregnancy induces immunosuppression, which could result in successful maintainance of pregnancy. This enhancement of adaptability to heat stress with pregnancy may be mediated by activation of placental progesterone and placental or pituitary beta-endorphin.     

Effects of continuous distraction on cartilage in a moving joint: An investigation on adult rabbits

An animal model, using distraction force on adult rabbits, was developed to study the effects of nonweight-bearing on articular cartilage in a moving joint. Histologic evaluation was used to compare the morphology of chondrocytes, safranin O intensity, cartilage thickness, and structural changes between the test and contralateral joints. At 3 and 6 weeks, the chondrocytes in superficial and intermediate zones were round, with an increase in cellular volume density and mean cell volume and with less metachromasia; the safranin O intensity and cartilage thickness were the same as in the controls. In cartilage of the 9-week group, mean cell volume decreased with cell cloning in the superficial zone, while numerical density increased and mean matrix volume per cell decreased in the superficial and intermediate zones. The cartilage, with a 34% reduction in thickness and a 53–72% decrease in safranin O intensity from the superficial to the deep zone, had superficial fibrotic proliferation, suface erosion or depression, ard tidemark irregularity. Continuous distraction in a moving joint caused morphological changes in chondrocytes prior to degeneration of cartilage. These results support the hypothesis that the forces perceived by cells may dictate their shape and then stimulate alterations in cellular biochemistry and matrix metabolism.     

Tetronothiodin, a novel CCKB receptor ligand, antagonizes cholecystokinin-induced Ca2+ mobilization in a pituitary cell line.

We found a novel nonpeptide CCKB receptor antagonist, tetronothiodin (Ro 09-1468), in the culture broth of Streptomyces sp. NR0489. The structure of the compound (C31O8H38S), which has a 19-membered ring with an alpha-acyltetronic acid and tetrahydrothiophene moiety, is completely different from that of any known CCK receptor antagonist. Tetronothiodin inhibited [125I]CCK-8 binding to rat brain CCKB receptors with an IC50 of 3.6 nM, whereas it showed only weak affinity for rat CCKA receptors (IC50 = 70 microM). As demonstrated autoradiographically, tetronothiodin concentration dependently inhibited [125I]CCK-8 binding to CCKB receptors in rat forebrain slices. The effects of tetronothiodin on cytosolic Ca2+ concentrations in GH3 cells, a rat anterior pituitary tumor cell line, were investigated with the fura-2 method. Tetronothiodin inhibited CCK-8-induced Ca2+ mobilization without affecting basal cytosolic Ca2+ concentrations. In conclusion, tetronothiodin is a new, potent and highly selective CCKB receptor antagonist. It is a useful tool for investigating the pharmacological and physiological roles of CCKB receptors.