Scalloped tongue is associated with nocturnal intermittent hypoxia among community-dwelling Japanese: the Toon Health Study.

Scalloped tongue is considered as a possible clinical finding of obstructive sleep apnoea (OSA). There are few evidence of the association between scalloped tongue and OSA. To examine the association between scalloped tongue and nocturnal intermittent hypoxia (NIH), a surrogate marker of OSA, among a general Japanese population. Study participants were 398 men and 732 women aged 30-79 years who participated in the Toon Health Study from 2011 to 2014. Scalloped tongue was classified into three categories: none, mild and moderate-to-severe. Moderate-to-severe NIH was defined as the 3% oxygen desaturation index of ≥15 events/h during sleep for one night with pulse oximetry. The multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for moderate-to-severe NIH were calculated according to scalloped tongue categories using a logistic regression model. There were 69 (6·1%) moderate-to-severe NIH cases in this population. The multivariable-adjusted ORs (95% CIs) of moderate-to-severe NIH were 1·59 (0·85-2·95) for mild and 2·39 (1·10-5·17) for the moderate-to-severe scalloped tongue group compared with the group without scalloped tongues. When stratified by overweight status (BMI <25 or ≥25 kg m-2 ), the respective ORs (95% CIs) were 2·83 (1·06-7·55) and 4·74 (1·28-17·49) among overweight individuals, and 0·94 (0·40-2·70) and 1·52 (0·57-4·05) among non-overweight individuals. Scalloped tongue was associated with higher prevalence of moderate-to-severe NIH among the general Japanese population and this association was more evident in overweight individuals.

Increased body fat in mice with a targeted mutation of the paternally expressed imprinted gene Peg3.

Peg3 encodes a C2H2 type zinc finger protein that is implicated in a novel physiological pathway regulating core body temperature, feeding behavior, and obesity in mice. Peg3+/- mutant mice develop an excess of abdominal, subcutaneous, and intra-scapular fat, despite a lifetime of lower food intake than wild-type animals. However, they start life with reduced fat reserves and are slower to enter puberty. These mice maintain a lower core body temperature, fail to respond to a cold challenge, and have lower metabolic activity as measured by oxygen consumption. Plasma leptin levels are significantly higher than in wild types, and Peg3+/- mice appear to have developed leptin resistance. Administration of exogenous leptin resulted in a significant reduction in food intake in wild-type mice that was not observed in Peg3+/- mutants. This mutation, which is strongly expressed in hypothalamic tissue during development, has the capacity to regulate multiple events relating to energy homeostasis.

Extract of vinegar "Kurosu" from unpolished rice inhibits the proliferation of human cancer cells.

The effects of the ethyl acetate extract of "Kurosu" (EK), Japanese traditional vinegar from unpolished rice, on the proliferation of a variety of human cancer cell lines were investigated by using the alamar blue assay. Cancer cell lines included colon adenocarcinoma (Caco-2), lung carcinoma (A549), breast adenocarcinoma (MCF-7), bladder carcinoma (5637), and prostate carcinoma (LNCaP) cells. EK inhibited the proliferation of all tested cell lines in a dose-dependent manner, with inhibition mostly pronounced in Caco-2 cells (up to 62% inhibition at a dose level of 0.025%). Flow cytometry of EK-treated Caco-2 cells showed a decrease in cell number in the G2/M phase and an increase in the sub-G1 phase (apoptotic). In addition, DNA fragmentation was detected in Caco-2 cells cultured with EK by immunostaining. RT-PCR analysis revealed p21 mRNA expression was induced in EK-treated Caco-2 cells. Moreover, PARP cleavage was promoted in EK-treated Caco-2 cells. These results suggest that EK causes G0/G1 arrest through p21 induction and, thus, is a potential apoptosis inducer in Caco-2 cells.

Apoptosis induction associated with cell cycle dysregulation by rice bran agglutinin.

Effects of rice bran agglutinin (RBA) on human monoblastic leukemia U937 cells were examined in comparison with those of wheat germ agglutinin (WGA) and Viscum album agglutinin (VAA). These lectins inhibit cell growth, and several lines of evidence indicate that the growth inhibition is caused by the induction of apoptosis. We observed that RBA induces chromatin condensation, externalization of membrane phosphatidylserine, and DNA ladder formation, features of apoptosis. DNA ladder formation was inhibited by a general inhibitor against caspases, which are known to play essential roles in apoptosis. Flow cytometric analysis revealed that RBA and WGA cause G2/M phase cell cycle arrest with increased expression of Waf1/p21, while cell cycle arrest was not observed for VAA. These data indicate that RBA induces apoptosis associated with cell cycle arrest in U937 cells, and suggest that the induction mechanism for RBA is similar to that for WGA, but different from that for VAA.

Evidence against singlet oxygen formation by sonolysis of aqueous oxygen-saturated solutions of Hematoporphyrin and rose bengal. The mechanism of sonodynamic therapy.

The possible role of singlet oxygen in the mechanism of sonodynamic therapy, the synergistic effect of ultrasound and certain sonosensitizers, was investigated. We used 4,4'-bis(1-p-carboxyphenyl-3- methyl-5-hydroxyl)-pyrazole (DRD 156), a sensitive new reagent which reacts specifically with singlet oxygen (1O2) but not with OH radicals, superoxide anion radicals or H2O2, to produce an EPR detectable signal. Sonolysis (48 kHz) of 90% D2O oxygen-saturated PBS solutions of Hematoporphyrin or Rose Bengal did not lead to the formation of detectable EPR signals of the semiquinone radical of DRD156. In contrast, the EPR signal of the semiquinone radical of DRD156 was observed during photoirradiation of Hematoporphyrin at 505 nm or of Rose Bengal at 544 nm. These results are inconsistent with a major role for singlet oxygen formation in the sonolysis of aqueous solutions of these compounds. An alternative mechanism for sonodynamic therapy involving peroxyl and alkoxyl radicals is discussed.

Microfluorocytometric detection of nuclear DNA damage to cancer cells in squamous cell carcinoma after hyperthermia.

An 84-year-old woman had a squamous cell carcinoma on her left thigh. Before operation, half of the tumor mass was irradiated with a microwave at 43 degrees C for an hour. After the hyperthermia, the tumor mass was removed, and the DNA instability was investigated by microfluorocytometric measurement of the cells stained with pararosaniline-Feulgen after hydrolysis with 2N HCl at 30 degrees C. The kinetic parameters k1, which is the rate constant for the generation of an apurinic acid, k2, which is the rate constant for the depolymerization of the apurinic acid and which reflects the degree of DNA instability for acid hydrolysis, and y0, which is the theoretical value of the single-stranded DNA present initially and reflects the degree of DNA damage, were determined by a computer fitting of the Bateman function to the hydrolysis curve plotting of the fluorescence intensity of the pararosaniline-Feulgen staining the apurinic acid against the different hydrolysis times. The parameter values y0 and k2 of the cells treated by hyperthermia were much higher than those of the cells treated without hyperthermia. It is our conclusion that this microfluorometric detection would be valuable as an evaluation method for a cancer therapy, although more data from other cancers and treatments will be needed.

Hyperthermic intravesical peplomycin perfusion treatment for bladder cancer.

Thirty-three patients with malignant bladder tumours were treated by hyperthermic intravesical perfusion. The study group included 25 patients with superficial T1 bladder tumours, 4 with T2 tumours and 4 with T3 tumours. Physiological saline solution containing 40 micrograms/ml peplomycin with/without 2% ethanol was used as a perfusate. Perfusion was carried out for 2 h 3 times per week and this regimen was repeated every other week, totalling 6 sessions in 3 weeks. Three patients achieved a complete response (CR), 5 a partial response (PR) (more than 50% tumour reduction), 8 a minimal response (MR) (25-50% tumour reduction) and the remaining 17 patients showed no response (NC). Complete, partial and minimal responses were obtained only in patients with T1 tumours. The NC patients included 4 with T2 and 4 with T3 lesions. Profuse haematuria from invasive tumour was markedly reduced after treatment. A major side effect was irritation of the bladder and urethra. Our results indicate that hyperthermic perfusion with ethanol and peplomycin is clinically safe, is accompanied by very little pain and may be useful for the management of superficial bladder tumours in elderly patients.

Combination effect of hyperthermia and photodynamic therapy on carcinoma.

We investigated the time course of hematoporphyrin oligomer uptake in squamous cell carcinoma transplanted into C3H mice after intraperitoneal injection by measuring its fluorescence intensity. The intensity peaked 83 hours after the injection. The tumors disappeared after an average of 4.12 days with a single application of photodynamic therapy or microwave hyperthermia 83 hours after hematoporphyrin oligomer injection. However, all the tumors treated with these single modalities regrew within 4 weeks after the treatments. Therefore, we investigated the therapeutic effect of microwave hyperthermia in combination with photodynamic therapy. As a result, the combination effect was strongest when high-dose therapy was used as the first choice, irrespective of the order of the treatments, and no tumor regrowth occurred for 45 days.

[Combination effect of photodynamic therapy and microwave hyperthermia on experimental squamous cell carcinoma in vivo].

We investigated the time course of Hematoporphyrin oligomer (HpO) uptake to squamous cell carcinoma (SCC) transplanted into C3H mice after intraperitoneal (i.p.)-injection by measuring its fluorescence intensity. The fluorescence intensity was maximum at 83 hr after the i.p.-injection. The tumors once disappeared by the single application of photodynamic therapy (PDT) or microwave hyperthermia at 83 hr after HpO i.p.-injection. However, all the tumors treated with these single modalities recurred within 4 weeks after the treatments. Therefore, we investigated the therapeutic effect of microwave hyperthermia in combination with PDT at 83 hr after HpO i.p.-injection. As the results, the combination effect was the strongest when high-dose therapy was used as the first choice of therapy, irrespective of the orders of the treatments and no tumor regrowth occurred over 45 days after tumor disappearance.

Whole bladder wall photoradiation therapy for carcinoma in situ of the bladder: a preliminary report.

Whole bladder wall photoradiation therapy, using a hematoporphyrin derivative as a sensitizer, the red light (wavelength 630 plus or minus 1.6 nm.) of an argon dye laser as the source of excitation energy and a motor driven laser light scattering optic, was performed in 2 patients with multicentric carcinoma in situ of the bladder. The total light dose was 10 J. per cm.2. Acute vesical inflammatory changes developed in the bladder wall lining, associated with a reduction of bladder capacity, which, however, disappeared within 3 months after photoradiation therapy. The anticancer effect of photoradiation therapy was followed by urinary cytologic and cystoscopic examinations for 4 months. Occasional discharges of clusters of vacuolated cancer cells or sheets of vesical detached cells in the urine were observed for 2 weeks after photoradiation therapy but, thereafter, repeat urinary cytologic and cystoscopic examinations revealed no malignancy.

Photoradiation therapy of bladder tumors.

Photoradiation therapy, in which hematoporphyrin derivative is activated by an argon-dye laser, was performed on 46 superficial bladder tumors in 9 patients. A fluorospectrophotometric study of biopsies from these tumors and normal mucosa revealed preferential hematoporphyrin derivative localization in malignant tissues. The tumor response was confirmed ultrasonographically in 36 stages Ta to Tl tumors. Treatment with 100 to 250 J./cm.2 obtained complete remission in 5 of 6 patients with tumors 1 cm. in size or less. For those with tumors up to 2 cm. in size the light intensity should be 300 mw./cm.2 for 5 to 10 minutes or more and the accumulated energy intensity of light dose should be 100 J./cm.2 or more. No patient with tumors more than 2 cm. in size had a complete remission.