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.

Amelioration of lacrimal gland inflammation by oral administration of K-13182 in Sjögren's syndrome model mice.

Regulation of the adhesion of mononuclear cells to endothelial cells is considered to be a critical step for the treatment of inflammatory diseases, including autoimmune diseases. K-13182 was identified as a novel inhibitor for these adhesions. K-13182 inhibited the expression of vascular cell adhesion molecule-1 (VCAM-1, CD106) on human umbilical vein endothelial cells (HUVECs) and on mouse vascular endothelial cell line (MAECs) induced by tumour necrosis factor (TNF)-alpha. K-13182 also inhibited the adhesion of mononuclear cells to these HUVECs and MAECs, indicating that K-13182 suppressed these adhesions mediated by cellular adhesion molecules including VCAM-1. To evaluate the therapeutic effect in autoimmune disease model mice, K-13182 was orally administered to non-obese diabetic (NOD) mice as Sjögren's syndrome (SS) model mice. Severe destructive inflammatory lesions were observed in the lacrimal glands of vehicle-treated control mice; however, 8-week administration of K-13182 inhibited the mononuclear cell infiltration into the inflammatory lesions of the lacrimal glands. In K-13182-treated mice, the decrease in tear secretion was also prevented compared to the control mice. In addition, the apoptosis and the expression of FasL (CD178), perforin, and granzyme A was suppressed in the lacrimal glands of K-13182-treated mice. Therefore, K-13182 demonstrated the possibility of therapeutic efficacy for the inflammatory region of autoimmune disease model mice. These data reveal that VCAM-1 is a promising target molecule for the treatment of autoimmune diseases as a therapeutic strategy and that K-13182 has the potential as a new anti-inflammatory drug for SS.

Cloning and characterization of a human brain Na(+)-independent transporter for small neutral amino acids that transports D-serine with high affinity.

We isolated a cDNA for the human homologue of system asc transporter Asc-1 from human brain. The encoded protein designated as hAsc-1 (human Asc-1) exhibited 91 % sequence identity to mouse Asc-1. Consistent with mouse Asc-1, hAsc-1 required 4F2 heavy chain for its functional expression in Xenopus oocytes. hAsc-1 exhibited the properties of amino acid transport system asc which transports small neutral amino acids in a Na(+)-independent manner. hAsc-1 transported D-serine at high affinity with a K(m) value of 22.8 microM. In brain, 2.0 kb mRNA was highly expressed. hAsc-1 gene was mapped to human chromosome 19, region q12-q13.1. Because of the high-affinity transport with the K(m) value close to the physiological concentration of D-serine, together with the high levels of expression in brain, hAsc-1 is proposed to play significant roles in the D-serine mobilization in brain.

Degeneration in vivo of rat hippocampal neurons by wild-type Alzheimer amyloid precursor protein overexpressed by adenovirus-mediated gene transfer.

In an attempt to elucidate the pathological implications of intracellular accumulation of the amyloid precursor protein (APP) in postmitotic neurons in vivo, we transferred APP695 cDNA into rat hippocampal neurons by using a replication-defective adenovirus vector. We first improved the efficiency of adenovirus-mediated gene transfer into neurons in vivo by using hypertonic mannitol. When a beta-galactosidase-expressing recombinant adenovirus suspended in 1 M mannitol was injected into a dorsal hippocampal region, a number of neurons in remote areas were positively stained, presumably owing to increased retrograde transport of the virus. When an APP695-expressing adenovirus was injected into the same site, part of the infected neurons in the hippocampal formation underwent severe degeneration in a few days, whereas astrocytes near the injection site showed no apparent degeneration. These degenerating neurons accumulated different epitopes of APP, and beta/A4 protein (Abeta)-immunoreactive materials were undetected in the extracellular space. A small number of degenerating neurons showed nuclear DNA fragmentation. Electron microscopic examinations demonstrated that degenerating neurons had shrunken perikarya along with synaptic abnormalities. Microglial cells/macrophages were often found in close proximity to degenerating neurons, and in some cases they phagocytosed these neurons. These results suggest that intracellular accumulation of wild-type APP695 causes a specific type of neuronal degeneration in vivo in the absence of extracellular Abeta deposition.

Arteriovenous malformations in the basal ganglia and thalamus: management and results in 101 cases.

OBJECT: Because arteriovenous malformations (AVMs) in the basal ganglia and thalamus are difficult to treat, the authors conducted a retrospective study to determine the best management strategy for these lesions. METHODS: The authors reviewed the management and outcome in 101 patients with AVMs treated between 1971 and 1995. In 15 conservatively treated patients, hemorrhage occurred in 71.4% (annual rate 11.4%), and the morbidity and mortality rates were 7.1% and 42.9%, respectively, during a mean follow-up period of 6.6 years. Total microsurgical resection was performed in 15 patients with no mortality resulting, but motor function deteriorated permanently in three of them (20%). Postoperative morbidity correlated well with the location of the AVM and with preoperative motor function. In cases of lenticular AVMs without motor weakness, a postoperative decrease in motor function was significantly more common than in the remaining patients. In patients with motor weakness before surgery, AVMs in the thalamus or caudate nucleus were successfully resected. Among 66 patients treated with gamma knife radiosurgery, three had permanent radiation-induced neurological deficits, and three others experienced bleeding (new bleeding in one case and rebleeding in two). The treatment-associated morbidity rate was 6.7%, and the actuarial rate of complete obliteration was 85.7% at 2.5 years. In five patients treated with embolization alone, the morbidity and mortality rates associated with the procedure or bleeding were 40% and 20%, respectively. The morbidity and mortality rates in the pre-gamma knife era were 22.2% and 22.2%, whereas those for the post-gamma knife era are currently 10.4% and 1.5%, respectively. CONCLUSIONS: These results indicate that conservatively treated AVMs are more likely to bleed and thus produce a high incidence of patient mortality. Multimodal treatment including radiosurgery, microsurgery, and embolization improved clinical outcomes by making it possible to treat difficult cases successfully.

Fluoroquinolone treatment failure in gonorrhea. Emergence of a Neisseria gonorrhoeae strain with enhanced resistance to fluoroquinolones.

BACKGROUND AND OBJECTIVES: Although emergence of clinical isolates of Neisseria gonorrhoeae with decreased susceptibilities to fluoroquinolones and treatment failures in gonorrhea have been reported, there have been no clinical reports that fluoroquinolone treatments actually select quinolone-resistant strains, nor have isolates that exhibited clinically significant resistance been analyzed for resistance mechanisms. GOALS: To report a case of fluoroquinolone treatment failure in gonorrhea and emergence of a posttreatment isolate with enhanced resistance to fluoroquinolones; and to study mechanisms of quinolone resistance in the isolates from this patient. STUDY DESIGN: A patient with gonococcal urethritis treated with ofloxacin, 200 mg, three times daily for 5 days is described. Pretreatment and posttreatment isolates were tested for minimum inhibitory concentrations (MICs) of antimicrobial agents and analyzed for alterations in DNA gyrase and topoisomerase IV. They were also examined for ofloxacin uptake. RESULTS: Treatment failure with multiple doses of ofloxacin was observed in this case of gonorrhea. The pretreatment isolate showed decreased susceptibilities to fluoroquinolones (MIC of ofloxacin, 1.0 mg/l; MIC of ciprofloxacin, 0.25 mg/l), and had amino acid changes of Ser-91-->Phe in GyrA and Ser-87-->Ile in ParC. The posttreatment isolate exhibited an increase in resistance to fluoroquinolones (MIC of ofloxacin, 8.0 mg/l; MIC of ciprofloxacin, 1.0 mg/l). This isolate had identical alterations in GyrA and ParC, but exhibited significantly reduced uptake of ofloxacin. This isolate also showed a small decrease in susceptibilities to cephalosporins. CONCLUSIONS: Alterations in DNA gyrase and topoisomerase IV confer clinically significant resistance to fluoroquinolones in N. gonorrhoeae strains. Treatment with multiple doses of fluoroquinolones is likely to bring about selection of more fluoroquinolone-resistant strains of N. gonorrhoeae and to influence susceptibilities to cephalosporins.

Experimental studies of stereotactic laser balloon hyperthermic treatment.

BACKGROUND AND OBJECTIVE: The hyperthermic treatment of small malignant brain tumors in basal ganglia and other eloquent cortical areas was investigated with a stereotactic Nd:YAG laser balloon unit. STUDY DESIGN/MATERIALS AND METHODS: An Ultra Line fiber (Heraeus Laser Sonics, CA) was inserted into a 6 F silicone balloon catheter, which caused the laser beam to be directed 80 degrees laterally. The balloon was inflated with physiologic saline to make the tumor tissue surrounding the laser fiber hypoxic. The hypoxia enhances the thermal effect on the tumor. The laser power was set at 5 watts (W) and a computer, programmed with specific parameters using feedback control was used to maintain the tissue 10 mm distant from the laser fiber at a temperature of 45 degrees C. Forty five minutes of hyperthermic treatment was applied to an implanted subcutaneous glioma in a rat. RESULTS/CONCLUSION: The thermally induced damaged in the tumor appeared as a fan-shape lesion extending at a 100 degrees angle from the laser beam axis. The entire tumor could be treated by rotating the laser fiber in the balloon catheter.

Analysis of guanine oxidation product via electron transfer in 5'-d(TTGGTA)-3'.

The photoirradiation of 5'-TTGGTA-3' in the presence of riboflavin with or without complementary oligomer 5'-ATACCAAA-3' was investigated by HPLC analysis. It was found that 2-aminoimidazol-4-one (Iz) containing hexamers, 5'-TTIzGTA-3' and 5'-TTGIzTA-3', were the major products.

Measurement of interleukin-4 and histamine in superficial cells of conjunctiva in patients with allergic conjunctivitis.

Interleukin 4 (IL-4) may play a role in the development of allergic disease. We questioned whether IL-4 related phenomenon occurred on the surface of the conjunctiva during allergic conjunctivitis. Ten patients with cedar pollen-allergic conjunctivitis and 10 patients with postsurgical conjunctivitis were enrolled in this study. Cells were collected by brush cytology from the upper palpebral conjunctiva. After the cells were cultured for 24 hours, the levels of IL-4, IgE, and histamine were measured in the supernatants. An ELISA was used for histamine and a highly sensitive sandwich ELISA for IL-4 and IgE. Conjunctival cells were also stained and fixed by May-Grunwalds stain solution. The number of superficial cells, especially lymphocytes, were compared in the two groups. The total number of cells collected by brush cytology did not differ in allergic vs., postsurgical conjunctivitis. Lymphocytes were similarly present in such specimens. The levels of IL-4 (p = 0.01) and histamine (p = 0.02) significantly increased in the specimens from patients with allergic conjunctivitis, although IgE was not detected in both groups. There was a correlation between the level of IL-4 and histamine (p = 0.0001). Conjunctival cells in allergic conjunctivitis produced a larger amount of IL-4 and histamine for cedar pollen compared to the postsurgical conjunctivitis. As with other allergic diseases, IL-4 may play a role similar to that of histamine in the development of allergic conjunctivitis.

[Transurethral radiofrequency thermotherapy for benign prostatic hyperplasia].

Transurethral radiofrequency thermotherapy was performed in 38 patients with benign prostatic hyperplasia using Thermex II (Direx) between December 1992 and June 1993, and its clinical efficacy was evaluated by analysing the subjective and objective responses following the treatment. Each patient was treated with an indwelling 16 Fr balloon catheter with electrode, in a single session of 90 minutes at 47-47.5 degrees C. The clinical efficiency was evaluated by total of AUA symptom score and objective findings in terms of maximum flow rate 12 weeks after treatment. The symptom score improved from 15.4 +/- 4.9 (mean +/- SD) to 7.3 +/- 5.2 25% or more improvement was found in 80% (20/25) of patients. No significant change was found in average of maximum flow rate before and after treatment, which were 8.9 +/- 4.1 (ml/sec) and 9.2 +/- 3.3, respectively. During the treatment no severe adverse effect except sense of heat and urgency was detected. Posttreatment urinary retension was found in 9 patients and catheters were indwelled in eight of them for a few days and prostatectomy was performed in one patients after 8 weeks of treatment. In four patients prostatectomy was performed between one day and 8 weeks after thermotherapy and histrogical effect on the resected specimen was examined. In the prostatic urethra, hemorrhage and inflammatory change were observed. However, in the prostatic tissue there was no necrotic region. Transurethral radiofrequency thermotherapy is safe and easy and it may be one of the useful treatments for benign prostatic hyperplasia.

Binding of biotinylated thrombin receptor peptide to cloned human thrombin receptor overexpressed in baby hamster kidney cells.

Baby hamster kidney (BHK) cells transfected with an expression vector for the human thrombin receptor, and then treated with basic fibroblast growth factor, were found to express specific and saturable binding sites for biotinylated thrombin receptor peptide (SFLLRNPNDKYEPF). Analysis of the binding to live BHK cells yielded an equilibrium dissociation constant (Kd) of 3.0 +/- 0.3 mu mol/l and a maximal binding capacity (Bmax) of 31.0 +/- 0.5 nmol/mg of protein. In competitive binding experiments, the thrombin receptor agonist peptide (SFLLRN), which is a strong inducer of human platelet aggregation, was the most potent competitor. In contrast, position 1 to 2 inverted peptides such as FSLLRNPNDKYEPF and FSLLRNP, which fail to induce for the platelet aggregation, were less potent. This simple and convenient binding assay system using the biotinylated thrombin receptor peptide as a labeled ligand and the cloned thrombin receptor overexpressed in BHK cells may be useful for exploring specific antagonists of the receptor.

Effects of 3'-angeloyloxy-4'-acetoxy-3',4'-dihydroseselin on cardiohemodynamics in anesthetized dogs.

Cardiohemodynamic effects of 3'-angeloyloxy-4'-acetoxy-3',4'-dihydroseselin (Pd-Ia) isolated from the Chinese medicinal plant Peucedanum praeruptorum Dunn were compared with those of diltiazem (Dil) in anesthetized open-chest dogs. Pd-Ia 3 mg.kg-1 increased coronary blood flow from 25 +/- 11 to 58 +/- 16 ml.min-1 (n = 7, P < 0.01) and decreased mean aortic pressure (MAP) from 13 +/- 2 to 8 +/- 1 kPa (P < 0.01), rate pressure product (RPP) from 1.9 +/- 0.5 to 1.3 +/- 0.3 MPa.bpm (P < 0.05), +dp/dtmax from 246 +/- 56 to 160 +/- 36 kPa.s-1 (P < 0.01) and systemic vascular resistance from 19 +/- 4 to 12 +/- 7 Pa.ml-1.min-1 (P < 0.05), together with an increase in HR. Dil showed effects similar to those of Pd-Ia except for a marked decrease in HR. The effects of Pd-Ia on MAP and RPP were approximately one-tenth as potent as those of Dil. The results demonstrated that Pd-Ia was a Ca2+ channel blocker.

Effects of a pyranocoumarin compound isolated from a Chinese medicinal plant on ischemic myocardial dysfunction in anesthetized dogs.

A pyranocoumarin compound, 3'-angeloyloxy-4'-acetoxy-3',4'-dihydroseselin (Pd-Ia), isolated from Bai-Hua Qian-Hu, a Chinese medicine, is known to possess a Ca2+ channel antagonist action. We examined the effect of Pd-Ia on cardiohemodynamics and regional myocardial dysfunction after transient ischemia in anesthetized open-chest dogs. I.v. injections of Pd-Ia (0.1-3.0 mg/kg, n = 7) significantly and dose dependently increased coronary blood flow and decreased mean aortic pressure, maximal rate of rise in left ventricular pressure, rate pressure product and systemic vascular resistance, together with a slight increase in heart rate. Diltiazem (0.03-1.00 mg/kg, n = 6) showed effects on the cardiohemodynamics similar to those of Pd-Ia, except for a marked decrease in heart rate. The effects of Pd-Ia on mean aortic pressure and rate pressure product were approximately 10 times less potent than those of diltiazem. In the second experiment, the effect of a 30-min infusion of Pd-Ia (0.15 mg/kg/min) or vehicle on regional myocardial dysfunction was examined in 16 anesthetized dogs subjected to a 15-min occlusion of the left anterior descending coronary artery followed by a 3-h reperfusion. Infusion of Pd-Ia was started 15 min before coronary occlusion. The vehicle caused a decrease in percent segment shortening throughout the reperfusion period (n = 8). However, Pd-Ia at the dose that produced no significant changes in cardiohemodynamics resulted in a marked improvement in percent segment shortening of the ischemic and reperfused myocardium (n = 8, P < 0.05 vs. control group).(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of diagnosis and treatment of Sjögren's syndrome in Japan and United States.

Today, as with western countries, diagnosis and treatment of Sjögren's syndrome (SS) patients in Japan are carried out by a team effort. The clinical manifestations of Japanese SS patients are quite similar also. There are, however, several minor modifications in the diagnosis and treatment of SS patients in Japan, which are presented in this article.

Growth and development of biofeedback: a bibliographic update.

Computerized literature searching techniques were used to examine publication patterns in the worldwide biofeedback literature. Searches were completed in the United States and in Japan for the years 1985 through 1987. The results were used to update the results of an earlier study that covered the years from 1964 through 1984. Publication growth curves were generated for several media, including scientific journal articles, books, doctoral dissertations, and popular magazine articles. Although publication of information about biofeedback remains active worldwide, there has been a declining trend in effect for the past several years. The American database grossly underestimated the number of Japanese biofeedback articles, and it is likely that the literatures of other countries outside of North America were similarly underestimated. Possible explanations for the various trends noted are discussed.

Furanoditerpenes of Fibraurea chloroleuca.

Fibraurin, chasmanthin, and palmarin were isolated from the stems of FIBRAUREA CHLOROLEUCA, Fam. Menispermaceae. The structure of the minor constituent, palmarin, was determined by X-ray crystallographic analysis.

An apparatus for a complimentary treatment of spasmodic torticollis.

We have developed an apparatus for treating spasmodic torticollis that can be used at home both during intensive therapy and follow-up. The refractoriness of spasmodic torticollis requires patients to practice biofeedback training partly on a home basis. However, it is usually difficult for spasmodic torticollis patients to provide and handle electromyographic (EMG) biofeedback training instruments. The present apparatus has 2 parts: first, a harness with a light source which is fixed on both shoulders; second, a photoreceptor, operant system for rewarding effect, and a digital recorder. The light is adjusted to strike the photoreceptor on the forehead when headposition is normal. Subjects are asked to keep the operant system--e.g. a radio--activated. They are trained in various postures as sitting, standing and walking. This apparatus provides a chance of home training to augment and maintain the effect during therapeutic sessions and the follow-up period.

[Immunohistochemical study on human colostral cells].

Colostrum contains a large number of cells and humoral defence factors that play an important role in the protection of neonates. While colostral cells have been characterized by immunohistochemical criteria, the function of these cells has been poorly understood. In this study, localization of immunoglobulins and other components in human colostral cells was examined by an immunofluorescence technique. The results obtained were as follows: Colostral cells reactive with polyvalent anti-human immunoglobulins were neutrophils and macrophages with a granular staining pattern. The predominant immunoglobulin in colostral cells was IgA, followed by IgM. A small amount of IgG was also found in these cells. The distribution of SC was similar to that of IgA and J-chain, suggesting the presence of secretory IgA in colostral cells. Coincidence of kappa chain and lambda chain in the same granules of neutrophils and macrophages suggests that these immunoglobulins were phagocytosed by neutrophils and macrophages. This conclusion was supported the results of the experiment which showed that incubation of peripheral blood neutrophils and monocytes with cell free colostrum resulted in the appearance of immunoglobulins in granules.

[Apparatus for heart rate biofeedback training].

Present study was undertaken to develop an apparatus for heart rate biofeedback training in clinical basis. The plethysmographic transducer was used for detection of pulses. The main part of this apparatus is composed of three systems in function, that is, an audiovisual feedback system of heart rate in analogue and digital manners, a reinforcement system of exteroceptive stimuli of light and/or sound and operant biofeedback system. Experimental inspection of the apparatus showed no problem except a case of angiospasm of fingers. Clinical trials revealed that this apparatus was available to the biofeedback control of heart beats in both normal volunteers and some cardiac patients.

Modulation of aldosterone secretion in frusemide-induced hypokalaemia.

To study the effect of hypokalaemia in the regulation of aldosterone secretion, repeated injections of frusemide (3 mg/kg) plus saline with or without simultaneous infusion of potassium chloride (1 mEq/kg/h) were performed in 24 conscious female rabbits for 7 h. Without potassium supplementation, the plasma renin activity (PRA) remained elevated throughout the study, while an initial increase (1 h to 3 h) in plasma aldosterone (PA) gradually returned to normal with reduction of the serum potassium. In rabbits on potassium supplements to prevent the development of hypokalaemia, both PRA and PA remained elevated. The incremental aldosterone response to administration of potassium chloride, angiotensin II or ACTH, was considerably smaller in potassium-depleted rabbits than in potassium-repleted rabbits. These results suggest that serum potassium modulates the effects of angiotensin II or ACTH on aldosterone secretion, and that a certain level of potassium is necessary to maintain the aldosterone secretory capacity of the adrenal gland.