No abstract

We have previously reported that both regressor (QR) and progressor (metastatic, QP) clones were obtained after the in vitro exposure of a mouse fibrosarcoma BMT-11 cl-9 to quercetin. In this study, we investigated possible mechanisms of spontaneous regression of QR clones as compared with tumorigenic QP and BMT-11 cl-9 tumor clones. We observed that BMT-11 cl-9 cells produced relatively high amounts of prostaglandin E2 (PGE2) during in vitro culture. The average production by 11 subclones of BMT-11 cl-9 cells was 9236 +/- 2829 pg/ml whereas that by 9 QR clones was 3411 +/- 2213 pg/ml (P less than 0.02). Indomethacin not only inhibited in vitro PGE2 synthesis by QP clones (high-PGE2 producers) but also the s.c. growth of QP clones in mice. Chronological changes in host immune responses to tumor-associated antigen were measured by cytotoxic T lymphocyte (CTL) activity examined after mixed lymphocyte/tumor cell culture of spleen cells obtained from tumor-bearing mice. The CTL activity disappeared abruptly in the spleen of QP-clone-bearing mice 21 days after the inoculation of tumors, whereas the spleen cells of QR-clone-inoculated mice retained their CTL activity. We determined that the mechanism responsible for the regression of these regressor clones is not due to any qualitative or quantitative increase in pre-existing membrane antigens, nor the emergence of new antigen(s) on the cell surface of the QR clones: nor was it due to enhanced susceptibility of QR clones to natural killer cells, lymphokine-activated killer cells and macrophages. These finding suggest that the regression mechanism of QR clones may be the diminished inhibition of host response to tumor-associated antigen caused by the reduced production of PGE2 by QR clones.

BackgroundObesity is a major risk factor for obstructive sleep apnea (OSA), and weight loss is necessary in the overall management of obese patients with OSA. However, primary care physicians can provide only limited weight loss with lifestyle interventions, usually reducing a patient’s body weight by only 2.5 kg or less after 6–18 months.Case presentationA 45-year-old Japanese man was referred to our clinic owing to obesity, daytime sleepiness, and snoring during sleep. His weight was 130.7 kg and his body mass index (BMI) was 41.0 kg/m2. He underwent polysomnography, which revealed OSA with an apnea–hypopnea index of 71.2 events/h (normal, <5 events/h). His laboratory results were as follows: thyroid stimulating hormone, >500 μIU/mL; free triiodothyronine, 1.4 pg/mL; free thyroxine, <0.15 ng/dL; thyroid peroxidase antibody, 10 IU/mL; thyroglobulin antibody, >4000 IU/mL; total cholesterol (TC), 335 mg/dL; high-density lipoprotein cholesterol, 45 mg/dL; triglycerides (TGs), 211 mg/dL; low-density lipoprotein cholesterol, 248 mg/dL; fasting blood sugar, 86 mg/dL; and glycated hemoglobin (HbA1c), 6.1 %. These results showed that he also had primary hypothyroidism (Hashimoto’s disease). Continuous positive airway pressure (CPAP), levothyroxine replacement, and a low-carbohydrate diet (LCD) were initiated. CPAP use and a euthyroid condition induced by 175 μg/day levothyroxine allowed the patient to proactively reduce his body weight. After 18 months, the patient achieved a weight reduction of 32.4 kg (25 % of his initial weight) and a BMI reduction of 10.2 kg/m2, as well as improved laboratory results, including an HbA1c level of 5.3 %, TC level of 194 mg/dL, and TG level of 89 mg/dL.ConclusionAn LCD may be an effective intervention for weight loss in obese Japanese patients with OSA. Further studies are needed to investigate the weight loss effect of an LCD compared with a conventional calorie-restricted diet. Hopefully, this case report will help to improve the management of obese Asian patients with OSA who typically consume a higher amount of carbohydrates.

We performed light and electron microscopic autoradiography of GABA and opiate receptors using 3H-muscimol and 3H-DAMA. Light microscopically, distribution of muscimol and DAMA binding sites was demonstrated by means of Texture Analysing System (Leitz). For electron microscopic autoradiography, selection of development method is important. The authors obtained silver grains in a pattern precisely localized to the cytoplasmic membrane, i.e, the receptor site by means of EAA development. We observed 3H-muscimol binding site in the neuropiles of the cerebellar molecular layer and the substantia nigra ultrastructurally. Receptor sites labeled with silver grains were located not only on the synaptic regions but also on the plasma membranes of the dendrites and axons not corresponding to synaptic sites. 3H-DAMA binding sites in the caudate nucleus and the amygdaloid nucleus were noted on the plasma membranes of the axons, dendrites and nerve cell somas, some corresponding to synapses, others not. Autoradiographical observation of neurotransmitter receptors has still problems to be solved. Nevertheless, this technique is very important to observe the morphological relationship between transmitters and their receptor sues.