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.

Surgical treatment of gastric cancer in Japan, trend from standardization to individualization.

Japan has a huge number of patients with gastric cancer and has developed various surgical treatments for this disease.This paper intends to introduce our strategies against gastric cancer. The Japanese Gastric Cancer Association was established in 1962. Its major purposes are promotion of basic and clinical researches and popularization of the latest knowledge and technologies. For the purposes, the association organized the annual scientific meeting and the nationwide registry by member hospitals, and published the Japanese Classification of Gastric Cancer (1) and the Treatment Guide Line (2). The nationwide registry reported that proportion of Stage-I cancer was 22.5% in 1963-66,which increased to 59.3% in 2008 (3,4,5). 11,261 patients with gastric resection were registered by 187 hospitals in 2008. 63 patients were died within 30 postoperative days and the direct death rate was 0.55%. 5 year survival rate (5YSR) was 37.5% for resected cases in 1963-66, which was improved to 70.1% in 2008. 5YSR was improved from 55.1% to 74.1% for Stage-II, and from 39.1% to 48.8% for Stage-III in the period. According to remarkable increase of early stage cancer, principle of surgical treatments was shifted from "€œextended and standardized surgery for radicality" €to "€œreasonable and individual surgery considering safety and quality of life"€. This trend produced a large variation in surgical treatments; namely 1) minimally invasive surgeries,2) function preserving surgeries, 3) optimal extent of lymph node dissection, and 4) aggressive but safe surgeries.Intention of this paper is to explain these procedures, the intentions, the indications, and the treatment results.

Isolation and characterisation of two cDNAs encoding the neuromedin U receptor from goldfish brain.

Intracerebroventricular administration of neuromedin U (NMU) exerts an anorexigenic effect in a goldfish model. However, little is known about the NMU receptor and its signalling system in fish. In the present study, we isolated and cloned two cDNAs encoding different proteins comprising 429 and 388 amino acid residues from the goldfish brain based on the nucleotide sequences of human NMU receptor 1 (NMU-R1) and receptor 2 (NMU-R2). Hydropathy and phylogenetic analyses suggested that these two proteins were orthologues of NMU-R1 and -R2 of goldfish. We established two human embryonic kidney 293 cell lines stably expressing putative NMU-R1 and -R2, respectively, and showed that NMU induced an increase in intracellular calcium concentration ([Ca(2+)](i)) in these cells. We examined the presence of NMU-R1 and -R2 in the goldfish brain by western blotting analysis using affinity-purified antisera raised against peptide fragments derived from these receptors. NMU-R1-specific and NMU-R2-specific antisera detected a 49-kDa and 45-kDa immunopositive bands, respectively, in the brain extract. The mass of each band corresponded to that of the deduced respective primary structures. Reverse transcriptase-polymerase chain reaction analysis showed that NMU-R1 and -R2 transcripts were detected in several tissues. In particular, both mRNAs were strongly expressed in the goldfish brain. By contrast, NMU-R2 mRNA was also expressed in the gut. These results indicate for the first time that NMU-R orthologues exist in goldfish, and suggest physiological roles of NMU and its receptor system in fish.

Randomized controlled trial for an effect of green tea-extract powder supplementation on glucose abnormalities.

OBJECTIVE: We examined whether green tea-extract powder supplementation improves glucose abnormality. METHODS: The study was conducted for volunteers who resided in eastern communities of Shizuoka Prefecture and who had fasting blood glucose levels of >or=6.1 mmol/l or nonfasting blood glucose levels of >or=7.8 mmol/l in a recent health check-up. Sixty subjects aged 32-73 years (49 males and 11 females) participated in the trial. The Early intervention group consumed a packet of green tea-extract powder containing 544 mg polyphenols (456 mg catechins) daily for the first 2 months and then entered the 2-month nonintervention period. The Later intervention group was observed for the first 2 months and then consumed green tea-extract powder as described above for the subsequent 2 months. Using the two-period crossover design, we analyzed the changes in fasting hemoglobin A1c level and other biomarkers in blood samples collected at baseline, 2 months and 4 months. RESULTS: A significant reduction in hemoglobin A1c level and a borderline significant reduction in diastolic blood pressure were associated with the intervention. The intervention caused no significant changes in weight, body mass index, body fat, systolic blood pressure, fasting serum glucose level, homeostasis model assessment index, serum lipid level or hypersensitive C-reactive protein. CONCLUSION: Daily supplementary intake of green tea-extract powder lowered the hemoglobin A1c level in individuals with borderline diabetes.

Isolation and characterisation of four cDNAs encoding neuromedin U (NMU) from the brain and gut of goldfish, and the inhibitory effect of a deduced NMU on food intake and locomotor activity.

In rodents, neuromedin U (NMU; U for its original effects examined in the uterus) is a multifunctional neuropeptide implicated in the regulation of the circulatory and digestive systems and energy homeostasis, especially appetite. However, there is no available information on the nature and physiological roles of NMU in fish. Therefore, we attempted to isolate and characterise transcripts encoding NMU from the brain and gut of the goldfish, and to examine the involvement of NMU in the regulation of feeding behaviour in this species. We identified four cDNAs encoding three NMU orthologs from the brain and gut. Putative peptides consisting of 21, 25 and 38 amino acid residues (NMU-21, NMU-25 and NMU-38) were deduced from their nucleotide sequences. Two mRNAs for NMU-25 were strongly expressed in the gut and weakly expressed in the brain and testis. By contrast, mRNA for NMU-21 was strongly expressed in the brain and weakly expressed in the peripheral tissues. Expression of mRNA for NMU-38 was weakly expressed only in the brain. Therefore, we examined the effect of feeding status on the expression of NMU-21 mRNA in the brain. Fasting for 7 days induced a significant decrease in the expression levels of NMU-21 mRNA in the brain. We also synthesised NMU-21 after deducing its C-terminal amide from the NMU-21 mRNA, and then investigated the effect of intracerebroventricular (i.c.v.) administration of NMU-21 on food intake and locomotor activity in the goldfish. NMU-21, injected i.c.v., suppressed food intake and locomotor activity in a dose-dependent manner. These results suggest that NMU orthologs exist in fish, and that the NMU-21 deduced from them can potently inhibit food intake and locomotor activity in goldfish.

Development of MBR with reduced operational and maintenance costs.

To reduce MBR O&M costs, a new MBR process that conducts efficient simultaneous biological nitrogen and phosphorus removal (BNR) was developed. In the development of this process, various approaches were taken, including reduction of power demand, chemical consumption and sludge disposal costs. To address power demand reductions, air supply requirements for membrane cleaning were reduced. The process adopted an improved membrane that requires less air for cleaning than conventional membranes. It also introduced cyclic aeration, which alternately supplies washing air to the two series of membrane units. Adoption of biological phosphorus removal eliminated chemical costs for phosphorus removal and contributed to the reduction of sludge disposal costs. By combining these technologies, compared to conventional MBR processes, an approximately 27% reduction in O&M costs was achieved.

Hypothalamic appetite-regulating neuropeptide mRNA levels in cachectic nude mice bearing human tumor cells.

We previously reported that the human melanoma cell line, SEKI, induces severe weight loss in nude mice. In the present study, we examined the expression of weight-regulating neuropeptide mRNAs in the hypothalamus of this cancer cachectic model by using a sensitive quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) method and in situ hybridization. mRNA levels of neuropeptide Y (NPY) and corticotropin-releasing hormone (CRH) in the whole hypothalamus were elevated significantly in the SEKI mice as compared with control mice. In situ hybridization showed that NPY and CRH mRNA were upregulated in the arcuate nucleus and the paraventricular nucleus, respectively. There were no significant differences in melanin-concentrating hormone (MCH), orexin (OX), and cholecystokinin mRNA levels between the SEKI and control mice. These results suggest that the NPYergic system is functioning in the rodent model of cancer cachexia; however, the role of the CRHergic system in energy homeostasis remains to be elucidated. This is the first report of the hypothalamic neuropeptide response to cachexia-inducing human cells.

Amino acid supplementation affects hematological and biochemical parameters in elite rugby players.

Individual amino acid supplementation affects various types of athletic performance. However, little information on combinations of amino acids is currently available. This study evaluated an amino acid mixture containing L-leucine, L-isoleucine, L-valine, L-arginine, and L-glutamine to 3.6 g of total amino acids per dose. Twenty-three rugby players were given 3.6 g, twice, daily of the amino acid mixture for 90 days (June-August 1994) and blood samples were collected for analyses in September 1993, March 1994, September 1994, and September 1995. After 90 days of supplementation, almost all of the athletes reported improvement in vigor and earlier recovery from fatigue. Significant increases (P<0.05) were observed in hemoglobin, RBC count, hematocrit, and serum iron by amino acid supplementation. Significant increases (P<0.05) were also noted in total cholesterol and low-density lipoprotein along with decreased (P<0.05) alkaline phosphatase. All values reverted to original levels when measured after one year of continued training without supplementation.

Node-positive mucosal gastric cancer: a follow-up study.

BACKGROUND: Lymph node metastasis from mucosal gastric carcinoma is rare and the prognosis of the patients has seldom been reported. METHODS: Forty-five patients with node-positive mucosal gastric cancer were studied. They accounted for 2.5% of 1770 patients with mucosal gastric cancer who underwent gastrectomy with lymphadenectomy at the National Cancer Center Hospital, Tokyo. The clinicopathological features were studied and the current clinical status was sought. RESULTS: The majority of patients (87%) were treated with D2 lymphadenectomy. The metastasis was confined to the perigastric nodes (pN1 by Japanese classification) in 30 patients (67%). The number of positive nodes was less than seven (pN1 by TNM) in 42 patients (93%). Two patients had para-aortic nodal metastasis. The median follow-up period was 11 years. Four patients died of definite or possible recurrent disease and the disease-specific 5- and 10-year survival rates were 95 and 89%, respectively. CONCLUSIONS: Although nodal metastasis is an important prognostic factor for gastric cancer, the prognosis was excellent as long as the primary tumor was confined to the mucosa and was treated with gastrectomy and lymphadenectomy.

Long-term inhalation of high-dose nitric oxide increases intraalveolar activation of coagulation system in mice.

Inhalation of nitric oxide (NO) is useful for the treatment of patients with pulmonary hypertension. However, the potential toxicity of inhaled NO is still unclear. Coagulation activation plays an important role in lung injury. We assessed the effect of low- and high-dose inhaled NO on the coagulation system in the intraalveolar space of mice. The animals were assigned to five groups (n = 6): [RA] group, mice exposed to fresh air alone; [RA+2 ppm NO] group, fresh air and 2 ppm NO; [RA+40 ppm NO] group, fresh air and 40 ppm NO; [RA+2 ppm NO+O(2)] group, fresh air, 2 ppm NO and O(2); and [RA+40 ppm NO+O(2)] group, fresh air, 40 ppm NO and O(2). Each group was treated for 3 wk. Lung specimens of [RA+40 ppm NO] and [RA+40 ppm NO+O(2)] groups showed significant nitrotyrosine immunoreactivity. BALF concentrations of total protein, thrombin and soluble tissue factor were significantly increased in mice of [RA+40 ppm NO] and [RA+40 ppm NO+O(2)] groups compared with [RA] group. However, BALF concentrations of total protein, thrombin, and soluble tissue factor were not significantly increased in mice of [RA+2 ppm NO] and [RA+2 ppm NO+O(2)] groups compared with [RA] group. Lung tissue factor mRNA expression was higher in the high-dose NO group than in the low-dose NO group. NO donor increased significantly tissue factor activity on alveolar epithelial cells. This study has shown for the first time that long-term inhalation of high, but not low, concentration of NO may activate the clotting system by increasing the lung expression of tissue factor.

Response of hypothalamic NPY mRNAs to a negative energy balance is less sensitive in cachectic mice bearing human tumor cells.

We selected three human cancer cell lines [human melanoma (SEKI), human melanoma (G361), and human neuroepithelioma (NAGAI)] that have an ability to develop cancer cachexia syndrome with and without accompanying anorexia and examined the hypothalamic levels of mRNAs for neuropeptide Y (NPY), melanin-concentrating hormone, and orexin. The body weight of sham-operated mice continued to increase, while mice of all tumor-bearing groups lost weight. Competitive reverse transcription-polymerase chain reaction analysis showed that, regardless of feeding status, NPY mRNA levels were elevated in all tumor-bearing mice compared with sham-operated mice, although to a lesser degree than weight-matched pair-weight mice. Melanin-concentrating hormone and orexin mRNA in the hypothalamus followed the same pattern as NPY, although most of the differences did not reach statistical significance. These results support the notion that the response of NPY mRNA to a negative energy balance is less sensitive in these rodent models of cancer cachexia.

A case of erythropoietic protoporphyria with liver cirrhosis suggesting a therapeutic value of supplementation with alpha-tocopherol.

Erythropoietic protoporphyria (EPP) was diagnosed in a 27-year-old man based on a typical clinical history, and a marked increase in erythrocyte and fecal protoporphyrin concentrations. Although liver disease is not a common feature in EPP, he had slight liver dysfunction. A percutaneous liver biopsy was performed and it showed minimal hepatocellular damage and many reddish brown pigment deposits in hepatocytes, Kupffer cells, portal histiocytes, bile canaliculi and small biliary radicles. Electron microscopic findings confirmed that these deposits were composed of protoporphyrin crystals. Liver biochemistry remained well for >2 years, but deteriorated rapidly and second liver biopsy obtained 28 months after the first biopsy revealed the development of liver cirrhosis. We treated the patient with intravenous administration of dl-a-tocopherol acetate (vitamin E; 500 IU/body/day). Following the administration of vitamin E, the concentration of protoporphyrin in erythrocytes decreased significantly and the liver function tests were improved. Sixteen weeks later he showed the full clinical and biochemical recovery suggesting that vitamin E supplementation might be useful in treating patients with EPP who developed liver damage.

Ataxia caused by mutations in the alpha-tocopherol transfer protein gene.

A 48 year old woman with ataxia with vitamin E deficiency is described. Gene analysis identified two point mutations in exon 1 of the alpha-tocopherol transfer protein (alpha-TTP) gene, one missense mutation and an upstream initiation codon mutation in the 5'-untranslated region (Kozak sequence). The latter mutation is the first one identified in the translation regulatory region. This mutation decreased the level of alpha-TTP protein expression. The clinical features included uncommon urinary disturbance and deafness and relatively rare retinitis pigmentosa. Supplementary therapy increased her serum vitamin E concentration to the normal range with mild improvement of the deep senses.

Targeting chemotherapy to solid tumors with long-circulating thermosensitive liposomes and local hyperthermia.

The effectiveness of the combination of long-circulating, thermosensitive liposomes and hyperthermia is described. Small-sized, thermosensitive liposomes that encapsulate doxorubicin (DXR-PEG-TSL (SUV)) have a prolonged circulation time and are extravasated to targeted solid tumors in vivo, where they preferentially release the agent in an anatomical site subjected to local hyperthermia. Liposomes were prepared by the incorporation of amphipathic polyethyleneglycol (PEG) to prolong their circulation time. DXR-PEG-TSL (SUV) was retained longest and was accumulated most efficiently in solid tumors in Balb/c mice. The combination of DXR-PEG-TSL (SUV) and hyperthermia at the tumor sites 3 h after injection, gave high concentrations of doxorubicin in tumor tissue and resulted in more effective tumor retardation and increased survival time. A large amount of DXR-PEG-TSL (SUV) was extravasated into the tumors during circulation for 3 h after injection, suggesting that the encapsulated drug was released into the interstitial spaces of the lesions by local hyperthermia. This system is expected to be clinically valuable for the delivery of a wide range of chemotherapeutic agents in the treatment of solid tumors.

Frontal lobe neuronal injury correlates to altered function in FIV-infected cats.

Six cats infected intravenously at 8 weeks of age with feline immunodeficiency virus Maryland isolate (FIV-MD), were evaluated at 8 and 14 months of age (6 months and 12 months postinfection, respectively) with high spatial resolution proton magnetic resonance spectroscopy (MRS) of the frontal cortex. Two separate control cat groups were evaluated at 8 months and 16 months of age. Single voxel two-dimensional high-resolution proton magnetic resonance imaging was performed using the PRESS sequence by selecting a 0.125 ml volume of interest in the medial frontal cortex. A significant reduction in both N-acetylaspartate (NAA) and NAA: choline ratio was found in the FIV 14-month-old group compared with FIV 8-month-old cats, and to the respective age-matched control 16-month-old cats. A negative correlation between NAA and CD4 lymphocyte count was seen in the FIV-14 group only. This group of FIV cats also exhibited a higher proportion of quantitative electroencephalographic relative slow wave activity (RSWA) that correlated to lower NAA content in the frontal cortical voxel. Although peripheral blood proviral load increased over time of infection, no correlation was found between proviral blood or lymph node load and NAA values, CD4 lymphocyte counts, or frontal cortical RSWA. Thus, this study demonstrated that neurologic functional disruption of the frontal cortex correlated strongly with neuronal injury and/or loss in FIV-MD-infected cats independent of peripheral proviral load. The ability to define in vivo neurodegeneration further in this animal model helps in understanding the neuropathogenesis of lentivirus infection, and possibly, a means to follow progression and reversibility during the initial stages of brain infection as therapeutic agents are identified.

Enhanced encapsulation of amphotericin B into liposomes by complex formation with polyethylene glycol derivatives.

PURPOSE: A highly efficient method was developed for the encapsulation of amphotericin B (AmB) in liposomes, and the mechanism involved was characterized. METHODS: AmB was encapsulated in dipalmitoylphosphatidylcholine/ cholesterol (DPPC/CH, 2:1) liposomes after complex formation with distearoyl-N-(monomethoxy poly(ethylene glycol)succinyl) phosphatidylethanolamine (DSPE-PEG). Hydration of lipids was done with 9% sucrose solution. RESULTS: The encapsulated amount of AmB was 111 microg/mg lipid, which was much higher than that obtained by the same method without DSPE-PEG (14 microg/mg lipid). The amount encapsulated increased with amount of DSPE-PEG used and with PEG molecular weight. Encapsulation efficacy was also influenced by the type of PEG derivatives used and by the modification of AmB, suggesting the involvement of complex formation between AmB and DSPE-PEG. Absorption and 31P-NMR spectral analyses indicated that interactions between the amino and phosphate groups and between the polyene and PEG moieties in AmB and DSPE-PEG, respectively, play an important role in the complex formation. CONCLUSIONS: Complex formation of AmB with DSPE-PEG allows the highly efficient encapsulation of the drug in liposomes. This simple technique should be applicable to other hydrophobic drugs.

Anastomotic recurrence after curative resection of a transverse colon carcinoma: a case report.

We report a case of anastomotic recurrence after curative surgery for transverse colon cancer in a 53-year-old man. The recurrence was first detected as a submucosal tumor 1.3 cm in diameter, located on the suture line, during an annual follow-up barium enema and colonoscopy. A repeat examination 3 months later showed the lesion to be a typical colon cancer, 2.5 cm in size, with a large ulcerated area. Right hemicolectomy was performed with curative intent. Anastomotic recurrence is much rarer after colonic resection than after anterior resection. This was the first time that we had detected a recurrent lesion as a submucosal tumor during annual follow-up examination.

[PEG-liposome in DDS and clinical studies].

The current status of newly developed polyethyleneglycol coated liposome (PEG-liposome) were described in this review. Liposomes have demonstrated considerable promise as a carrier for the delivery of drugs in vivo. However, one of the drawback is that most liposomes intravenously injected into animals are rapidly removed from the blood circulation by uptake primarily in the cells of reticuloendothelial system (RES). It has been found that PEG-liposome are not readily taken up by the macrophages in the RES and hence stay in the circulation for a relatively long period of time. Pharmacokinetic analysis and therapeutic studies with tumor bearing mice revealed that PEG-liposomes have considerable potential as drug carriers for cancer therapy. Elevated liposome accumulation has been found in the tumor bearing mice model system. Results from clinical studies with doxorubicin encapsulated into PEG-liposomes (DOXIL) in AIDS-related Kaposi's sarcoma revealed an increased therapeutic efficacy compared to free-drug. These new formulations of long-circulating liposomes (PEG-liposome) offer the development of immunoliposomes with both long survival times in circulation and target recognition being retained in vivo. Fab'-PEG-immunoliposome was newly designed to gain long-circulating enough to extravasate to the targeted solid tumor in vivo. An ultimate goal of Fab'-PEG-immunoliposome is the incorporation of a fusogenic molecules that would induce fusion of liposome following their binding to the target cells or their internalization by endocytosis. Such liposomal formulations should be useful for endocytotic internalization of plasmid DNA and other bioactive materials.

Pectins in extracellular polysaccharides from a cell-suspension culture of Mentha.

Pectin constituents, which were about 70 w/w% of extracellular polysaccharides (ECP) from a cell-suspension culture of Mentha, were purified by gel filtration chromatography, and their sugar composition and linkage were investigated. Two major constituents identified were (1-->3)-linked galactan carrying arabinosyl residues on C-6 and (1-->4)-alpha-linked galacturonan partially interspersed with (1-->2)-linked rhamnosyl resides. Acetylated or methylated pectins were not identified on 1H-NMR analysis.

Extended unilateral anesthesia. New technique or paravertebral anesthesia?

BACKGROUND AND OBJECTIVES: The authors previously reported a case in which injection of local anesthetic posterior to the endothoracic fascia at the T11 vertebral level gave rise to extended analgesia in thoracic and lumbar dermatomes. They now report a study in which this type of anesthesia was used in patients undergoing herniorrhaphy. METHODS: A 12-mL dose of 2% mepivacaine was injected at the T11 level posterior to the endothoracic fascia in 15 patients. RESULTS: On average, seven dermatomes could be blocked with this dose and with a single injection. Nine patients experienced adequate analgesia and underwent operation with no additional sedation. In three patients the block resulted in inadequate analgesia, and additional sedative drugs were used. Three patients experienced no analgesia and were given general anesthesia CONCLUSION: Injection of local anesthetic posterior to the endothoracic fascia resulted in extended unilateral anesthesia that was adequate for herniorrhaphy in 9 of the 15 patients (60%) studied.