Emergent Spin-Gapped Magnetization Plateaus in a Spin-1/2 Perfect Kagome Antiferromagnet.

The two-dimensional spin-1/2 kagome Heisenberg antiferromagnet is believed to host quantum spin liquid (QSL) states with no magnetic order, but its ground state remains largely elusive. An important outstanding question concerns the presence or absence of the 1/9 magnetization plateau, where exotic quantum states, including topological ones, are expected to emerge. Here we report the magnetization of a recently discovered kagome QSL candidate YCu_{3}(OH)_{6.5}Br_{2.5} up to 57 T. Above 50 T, a clear magnetization plateau at 1/3 of the saturation moment of Cu^{2+} ions is observed, supporting that this material provides an ideal platform for the kagome Heisenberg antiferromagnet. Remarkably, we found another magnetization plateau around 20 T, which is attributed to the 1/9 plateau. The temperature dependence of this plateau reveals the presence of the spin gap. The observation of 1/9 and 1/3 plateaus highlights the emergence of novel states in quantum spin systems.

Low serum potassium levels and risk of type 2 diabetes: the Toranomon Hospital Health Management Center Study 1 (TOPICS 1).

AIMS/HYPOTHESIS: Evidence has suggested that low serum potassium concentrations decrease insulin secretion, leading to glucose intolerance, and that hypokalaemia induced by diuretics increases the risk for diabetes in hypertensive individuals. However, no prospective study has investigated the association between serum potassium and the development of type 2 diabetes in a healthy cohort comprised of Asian individuals not being administered antihypertensive medications. This study aimed to investigate whether low serum potassium is associated with increased risk of type 2 diabetes in apparently healthy Japanese men. METHODS: We followed 4,409 Japanese men with no history of diabetes, use of antihypertensives, renal dysfunction or liver dysfunction (mean ± SD age, 48.4 ± 8.4 years). Cox proportional hazards regression was used to estimate HRs for incident diabetes (fasting plasma glucose level ≥ 7.0 mmol/l, HbA(1c) ≥ 6.5% or self-reported) including serum potassium concentration as either a categorical or a continuous variable. RESULTS: During a 5 year follow-up, 250 individuals developed type 2 diabetes. The lowest tertile of serum potassium (2.8-3.9 mmol/l) was independently associated with the development of diabetes after adjustment for known predictors (HR 1.57 [95% CI, 1.15-2.15]) compared with the highest tertile (4.2-5.4 mmol/l). Every 0.5 mmol/l lower increment in the baseline serum potassium level was associated with a 45% (12-87%) increased risk of diabetes. CONCLUSIONS/INTERPRETATION: Mild to moderately low serum potassium levels, within the normal range and without frank hypokalaemia, could be predictive of type 2 diabetes in apparently healthy Japanese men.

Factors associated with inappropriate weight loss attempts by early adolescent girls in Japan.

Attempting to lose weight by normal or underweight adolescent girls is a serious issue in many countries. It has been reported that the mode of attempted weight loss does not differ between normal weight and overweight girls. These inappropriate weight loss attempts (IWLA) by normal or underweight adolescent girls is associated with various health issues, but factors associated with IWLA have only been marginally elucidated. In this study, we applied a single multivariate regression analysis to clarify independent factors for IWLA. Study subjects were 134 pairs of early adolescent girls (aged 12-15) and their mothers. In addition to IWLA, many factors including height, weight, body image, perceived weight status, depressive symptoms, media influence and self-esteem were surveyed in both mothers and daughters and subjected to multivariate analysis. Approximately half of girls surveyed had IWLA, even though all were of normal weight and 62.9% knew that they were of normal weight. IWLA were independently associated with depressive symptoms (OR (95% CI); 2.80 (1.21-6.50), p=0.016) independent of actual or perceived weight status. Factors significantly associated with IWLA by the girls were percentage deviation of weight from standard weight (%DW) and media influence on the girls themselves, and media influence on and self-esteem of their mothers. IWLA, which were frequently observed among early adolescent girls even among those of normal weight, were closely related to depressive status. IWLA were significantly associated with not only factors related to the girls (1.09 (1.04-1.14), p=0.001), but also with maternal psychological factors (1.06 (1.00-1.13), p=0.035) conveyed by the media. Future prospective or interventional studies are required to clarify whether these factors could be targeted in an effort to prevent IWLA.

Effects of combination of benzylpenicillin and fosfomycin on penicillin-resistant Streptococcus pneumoniae.

The in vitro activity of benzylpenicillin in combination with fosfomycin against 51 clinical isolates of penicillin-resistant Streptococcus pneumoniae [minimal inhibitory concentrations (MICs) of benzylpenicillin > or = 0.5 mg/liter] was investigated. The fractional inhibitory concentration (FIC) index using the checkerboard method ranged from 0.38 to 0.75 (mean: 0.63). A synergy was also demonstrated in the killing curve on S. pneumoniae TW-1303 (MIC of benzylpenicillin, 2 mg/liter; MIC of fosfomycin, 32 mg/liter: FIC index, 0.38). Fosfomycin inhibited the production of all penicillin-binding proteins (PBP) except PBP 2B of S. pneumoniae TW-1303 and it decreased that of PBP 2B when it was combined with benzylpenicillin. These results suggest that the combination of benzylpenicillin and fosfomycin could be considered as the alternative treatment of penicillin-resistant pneumococcal infections.

Similarity of antibiotic resistance patterns and molecular typing properties of methicillin-resistant Staphylococcus aureus isolates widely spread in hospitals in New York City and in a hospital in Tokyo, Japan.

One hundred and forty-three single-patient methicillin-resistant Staphylococcus aureus (MRSA) isolates collected during April-June, 1997, and February, 1998, in a hospital in Tokyo, Japan, were characterized by molecular typing techniques that involved hybridization of ClaI restriction digests with the mecA- and Tn554-specific DNA probes and determination of macrorestriction patterns of SmaI-digested chromosomal DNA by pulsed-field gel electrophoresis (PFGE). A large proportion (76%) of the isolates carried the mecA polymorph I, Tn554 pattern A, and PFGE pattern A (clonal type I:A:A), which was the same as the clonal type of an MRSA widely spread in hospitals in New York City and hospitals in neighboring New Jersey, Connecticut, and Pennsylvania. Also similarly to the New York clone, most of the MRSA isolates from the Japanese hospital were resistant to penicillin, ciprofloxacin, erythromycin, tetracycline, and high concentrations (500 microg/ml) of spectinomycin, but were susceptible to chloramphenicol, sulfamethoxazole-trimethoprim, and rifampin. All of the 143 MRSA isolates had vancomycin MICs < or = 2 mg/L.

Effects of food intake and age on the pharmacokinetics of AS-924, a novel ester-type cephem antibiotic. Comparison with cefpodoxime proxetil.

The effects of food intake and age on intestinal absorption of AS-924, a novel prodrug-type cephem antibiotic, were examined in 16 healthy adult volunteers (eight young volunteers and eight elderly volunteers) by the cross-over method, using cefpodoxime proxetil (CPOD-PR) as the control drug. The gastrointestinal absorption of AS-924 and CPOD-PR was increased slightly by food intake and the extent of increase was slightly greater after administration of CPOD-PR. The absorption of AS-924 was not affected by age, whereas intestinal absorption of CPOD-PR increased with age. In conclusion, these results confirmed that AS-924 has the unique characteristics as a novel prodrug and that its absorption is less likely to be affected by food intake and age.

Effect of antacid pretreatment on the pharmacokinetics of AS-924, a novel ester-type cephem antibiotic--comparison with cefteram-pivoxil.

The effect of pretreatment with ranitidine, an antacid, on the absorption of AS-924, a novel prodrug-type cephem antibiotic derived from ceftizoxime (CTIZ), was examined in eight healthy adult male volunteers by the cross-over method, using cefteram-pivoxil (CTER-PI) as the control drug. The C(max) and area under the concentration (AUC) values and cumulative urinary excretion rate (0-24 h) of cefteram (CTER) after administration of CTER-PI decreased by 32, 38 and 37%, respectively, in the ranitidine pretreatment group whereas those of AS-924 were not affected by the antacid. The urinary levels of pivaloyl-carnitine determined to evaluate the solubility of these antibiotics in the gastrointestinal tract suggested that this was not affected by ranitidine. These results indicate that the absorption of CTER-PI was affected by pretreatment with ranitidine largely due to inactivation of this antibiotic in the gastrointestinal tract at high pH rather than to a decrease in solubility. In contrast, isomerization of AS-924 was hardly induced by the elevation of pH, thus demonstrating that AS-924 was less likely to be affected by pretreatment with antacids.

Purification of canine alpha-fetoprotein and alpha- fetoprotein values in dogs.

Canine alpha-fetoprotein (AFP) was purified by a two step method. Anti-dog AFP antiserum was produced by immunizing rabbits with canine fetal serum proteins that failed to bind to an anti-dog whole adult serum affinity column. Canine AFP was then purified from amniotic fluid using affinity chromatography with anti-dog AFP antiserum. The bound protein was then eluted and further purified by passage through an anti-dog whole adult serum column. The non-binding protein's purity and specificity was confirmed by immunoelectrophoresis, double-diffusion, sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and cross-reactivity with anti-human AFP. The molecular weight of canine AFP was approximately 66,000 by SDS-PAGE. Normal adult dogs had serum AFP levels of 7-63 ng ml-1. Levels of AFP were not altered by pregnancy but did show a small peak 2 days following parturition. Newborn puppies had serum AFP levels of 14.08 +/- 5.94 mg ml-1 at birth. By 1 week of age, serum AFP had fallen to 0.766 +/- 0.758 mg ml-1. AFP values in newborn puppies are thus considerably higher than those previously reported in humans, pigs and cattle.

Pharmacokinetic studies on the concomitant administration of piperacillin and cefazolin, and piperacillin and cefoperazone in rabbits.

The pharmacokinetics of each drug on the concomitant administration of piperacillin (PIPC) and cefazolin (CEZ) or cefoperazone (CPZ) were studied in rabbits. When rabbits received the consecutive drip infusion administration of CEZ (0.71 mg/kg/minute) and PIPC (1.38 mg/kg/minute) and likewise of CPZ (0.72 mg/kg/minute) and PIPC (1.54 mg/kg/minute) for 1 hour, respectively, the serum half-lives of CEZ and CPZ were respectively prolonged about 1.8 and 1.6 times during drip infusion of PIPC than administered alone. However, when the sequence of administration were reversed, the serum levels of PIPC were not affected by the consecutive drip infusion administration of CEZ and CPZ. To study these findings in detail, the single intravenous dose of 20 mg/kg of CEZ and CPZ were administered under drip infusion of PIPC (2.65-2.93 mg/kg/minute). The serum half-lives of CEZ and CPZ were also prolonged about 5.4 and 1.9 times, respectively, whereas urinary excretion of CEZ, and urinary and biliary excretion of CPZ were reduced by PIPC. Moreover, when the single intravenous dose of 20 mg/kg of PIPC were administered under drip infusion administration of CEZ (0.96-2.60 2.60 mg/kg/minute), the pharmacokinetics of PIPC was not affected by the presence of CEZ. However, under drip infusion administration of CPZ (2.60-2.70 mg/kg/minute), the PIPC serum half-life was prolonged about 1.4 times, and biliary excretion of PIPC was reduced but urinary excretion was not. From the results of renal clearance experiments, tubular secretion appeared to be the predominant mechanism of renal elimination for these three drugs. These results indicate that PIPC influences the pharmacokinetics of both drugs by the competitively inhibiting tubular secretion in CEZ, and tubular secretion and hepatic transport system in CPZ. Therefore, in this respect PIPC seems to have probenecid-like action.

Nutritional implications of high-iodine egg diet in rats: effects on lipid metabolism and thyroid function.

The effects of a diet including high-iodine eggs, containing much higher amounts of iodine than ordinary eggs, were investigated on lipid metabolism and thyroid function in rats. To a non-purified diet was added at the 1% (w/w) level ordinary egg power (OE diet: 35 micrograms iodine/100 g diet) or high-iodine egg powder (IE diet: 392 micrograms iodine/100 g diet). At 7 months and 19 months, feeding of the IE diet resulted in a lowered serum triacylglycerol level, elevated tissue lipoprotein lipase activity and a lowered lipid peroxide level in the brain. Although the serum total iodine level was 5 times higher in animals given the IE diet than in those given the OE diet, serum levels of thyroid-related hormones (TSH, T3 and T4) were not affected by feeding of the IE diet. In animals exposed to cold and given antithyroid drug treatment, the IE diet seemed to improve age-related defects in thermogenic and thyroid hormone responses to cold, and also to confer resistance to the antithyroid drug. These results suggest that iodine ingestion through high-iodine eggs modulates both lipid metabolism and thyroid function in rats.

Effects of the long-term (17-19 months) feeding of high-iodine eggs on lipid metabolism and thyroid function in rats.

The present paper describes the effects of long-term (17-19 months) feeding of high-iodine eggs on lipid metabolism and thyroid function of rats, and also the effects of inorganic iodine on lipid metabolism. Rats were meal-fed on a diet containing 1% (w/w) of ordinary egg powder (OE diet as control: 35 micrograms I/100 g) or high-iodine egg powder (IE diet: 392 micrograms I/100 g). After the 19-month dietary treatment, rats fed on the IE diet, compared with the controls, showed a higher tissue lipoprotein lipase activity, a lower lipid peroxide level in the brain and a trend toward lower serum triacylglycerol levels and body fat storage without alterations in serum levels of thyroid-related hormones (TSH, T3 and T4). From the results of cold exposure and anti-thyroid drug-treatment conducted on rats fed on the OE and IE diets for 17 months, high-iodine eggs seemed to improve the age-related defects in thermogenic and thyroid hormone responses to cold, and also to result in a resistance to the anti-thyroid drug. The effects of the IE diet on lipid metabolism of rats were partly exhibited by feeding of the OE diet with an equivalent amount of iodine added as KI or KIO3. Thus, it is suggested that iodine ingestion through high-iodine eggs modulates both lipid metabolism and thyroid function in rats.

Histopathological study on rats fed iodine-enriched eggs long-term (7 and 19 months).

A histopathological study was conducted on rats fed on a diet containing iodine-enriched eggs over the long term, 7 and 19 months. A laboratory powder chow was added at the 1% (w/w) level with ordinary egg powder (ordinary egg diet as control: 35 micrograms iodine/100 g diet) or iodine-enriched egg powder (iodine-enriched egg diet: 392 micrograms iodine/100 g diet). The animals were meal-fed twice a day and allowed unrestricted voluntary wheel-running. In general, organs, tissues and endocrine glands including thyroid glands from rats of the iodine-enriched egg diet group exhibited no significant difference in histopathological features as compared with those of the ordinary egg diet group. These results suggest that long-term feeding of a considerable amount of iodine through an iodine-enriched egg diet did not cause any specific excess-iodine toxicity.

Influences of feeding of high-iodine eggs on hypo- and hyperthyroid rats.

The effects of the feeding of high-iodine eggs to rats with an abnormal thyroid status were investigated. Rats were fed for one week on a commercial diet supplemented with propylthiouracil (PTU) (10 mg/100 g diet) or thyroxine-Na (240 micrograms/100 g diet) respectively, to induce hypo- or hyperthyroidism, and then further fed for 4 weeks on the respective drug-supplemented diets, containing 1% (w/w) of either ordinary or high-iodine egg powder. Control (euthyroid) rats were maintained on the commercial diet. The induction of a hypothyroid state resulted in thyroid hyperplasia, with decreased thyroid iodine content, altered serum thyroid relating hormone levels (increased TSH and decreased T3 and T4), elevated serum total cholesterol and reduced serum triacylglycerol (TG) levels, and also increased muscle and adipose tissue lipoprotein lipase (LPL) activities. In contrast, in the hyperthyroid animals, thyroid atrophy, as well as decreased serum TSH and increased T3 and T4 levels, was associated with reduced serum total cholesterol level and muscle LPL activity. There were no essential differences between animals given high-iodine and ordinary eggs in either hypo- or hyperthyroid state, although the effects of PTU treatment on the thyroid and serum TG level appeared to be slightly lesser in rats given high-iodine eggs than in those given ordinary eggs. It is concluded that high-iodine eggs did not have any side-effect on either hypo- or hyperthyroid rat in this study.

Iodine content of various meals currently consumed by urban Japanese.

Various meals being currently consumed by urban Japanese were determined for iodine. The meal samples were collected in 1982 and 1984. The habitual daily home meals of 4 middle-aged Japanese living in urban areas contained 45-1,921 micrograms (mean; 362, 361, 429 and 1,023 micrograms, respectively) of iodine per day. The regular meals served in two university hospitals contained 95-287 micrograms (mean; 195 micrograms) and 89-4,746 micrograms (mean; 1,290 micrograms) of iodine per day, respectively, and the diets for diabetes mellitus contained 59-144 micrograms (mean; 96 micrograms) of iodine per day. In the daily meals containing iodine exceeding ca. 300 micrograms, some kinds of seaweeds and, in some cases, several foods containing a red food color with low iodine bioavailability, erythrosine, provided a large portion of iodine. The iodine contents of refectory meals in a university were 47-203 micrograms (mean; 113 micrograms) per meal and those of lunches in two elementary schools were 25-31 micrograms (mean; 27 micrograms) and 18-43 micrograms (mean; 36 micrograms) per lunch, respectively. These results suggest that the current daily iodine intake of urban Japanese is not great and that erythrosine elevates the iodine content of meals.

Thyroxine-induced molting and gonadal function of laying hens.

Twenty laying hens, 238 days of age, were divided into four groups which received daily intramuscular injections of L-thyroxine (T4) (0, 20, 100, or 500 micrograms/kg body weight per day) for 4 weeks. There was no change in body weight or egg production rate of the control (0 microgram T4) or of 20 and 100-micrograms T4 groups over time. Body weight and egg production of the 500 micrograms T4 group decreased markedly and molting started 10 days after T4 injection. Circulating iodothyronine (T4), triiodothyronine (T3), and reverse triiodothyronine (rT3) of the 500-micrograms T4 group increased markedly (30 to 150 times those of the control group) whereas serum luteinizing hormone and progesterone declined after one week and estradiol after two weeks. We concluded that a large dose of T4 (500 micrograms T4/kg, body weight per day) induced an increase in circulating iodothyronine levels, decreased secretion of gonadotropin and sex steroid hormones, and induced molting.

[A Case of central venous catheter-related infection with Malassezia sympodialis].

We report a 63-year-old male with central venous catheter-related infection caused by Malassezia sympodialis after total gastrectomy for a gastric cancer. He had fever and his leukocyte counts and C-reactive protein were elevated 14 days after his operation. After his central venous hyperalimentation catheter was removed, the inflammatory signs immediately disappeared, suggesting an intravenous catheter-related infection. A yeast-like fungus was cultured in brain-heart infection semi-solid agar ten days later, and was diagnosed morphologically as Malassezia sp. This strain was identified as M. sympodialis by Tween assimilation test and was confirmed by whole-sequence of internal transcribed spacer 1 regions (ITS1). This is the first report of catheter-related infection caused by M. sympodialis. This strain grew and was subcultured on CHROMagar Candida, potato dextrose agar and Sabouraud agar. There have been no reports of such a lipid-independent Malassezia sp. except for M. pachydermatis. The mechanism of lipid independence of this strain is undetermined and future work is needed. Malassezia sp. is receiving increased attention as an etiologic pathogen of catheter-related fungemia in clinical microbiology laboratories and infectious disease sections.

[Microbiological and clinical studies of vancomycin resistant Leuconostoc spp. and Pediococcus spp. isolated from septicemia patients].

We described three septicemia cases in which blood cultures yielded gram-positive cocci identified as Leuconostoc spp. and Pediococcus spp. Patients were three male adults aged 63 to 71 years with severe underlying diseases, pancreatic cancer, esophageal cancer and diabetes mellitus with chronic renal failure. They had fever and chills at the onsets of septicemia with acute obstructive suppurative cholangitis, acute pneumonia, and infection complicated with invasion sites of esophageal cancer contagious to bronchus and subcutaneous tissue. Blood cultures yielded catalase and oxidase negative highly vancomycin-resistant (MIC: 1024 micrograms/ml <) gram-positive cocci showing alpha or gamma hemolysis on blood agar plates. Two cases were polymicrobial infections. In one case with esophageal cancer, clinical symptoms persisted after the start of antimicrobial chemotherapy and the patient died 10 days later associated with complications of esophageal cancer. Leuconostoc lactis, Leuconostoc mesenteroides subsp. dextranicum, and Pediococcus acidilactici wee identified by physiological reactions. These strains were also highly resistant to teicoplanin and fosfomycin, and tolerant to all rested beta-lactams such as benzylpenicillin. This is the first report in Japan to our knowledge on the identification of Leuconostoc spp. and Pediococcus spp. isolated from human infectious diseases.

[Microbiological and clinical studies of infective endocarditis due to nutritionally variant streptococci].

We report four cases of infective endocarditis due to nutritionally variant streptococci (NVS) that occurred between 1981 and 1991. Three female and one male patients had underlying heart diseases. Causative organisms showed satellitism to staphylococci. Two strains were identified as S. adjacens and the other two were identified as S. defectivus by DNA-DNA hybridization. All strains had tolerance and one strain had resistance to benzylpenicillin (MIC 4 micrograms/ml). This penicillin-resistant strain also had tolerance to gentamicin. There was no synergism of benzylpenicillin and gentamicin against this strain by a killing curve in vitro. A 11-year-old female patient with infective endocarditis due to this strain, who had a transposition of great arteries, had large vegetations in external conduits by the Rastelli's operation. Some intensive antimicrobial chemotherapies were unsuccessful and a surgical replacement of the conduits must be done in this case. Since infective endocarditis due to NVS is not rare in Japan, NVS should be considered for the causative organisms in culture negative endocarditis.

[A fulminating case of Edwardsiella tarda septicemia with necrotizing fasciitis].

A 67-year-old Japanese male, suffering from liver cirrhosis with hepatoma, was admitted to the Yokohama National Hospital because of ascites retention. On physical examination, his abdomen was massively distended with ascites and his lower extremities were edematous. Laboratory findings on admission revealed hypoalbuminemia, moderate icterus, pancytopenia and hepatitis C virus antibody positivity. After admission, abdominal distention and edema were improved with the use of diuretics. On the 15th day of hospitalization, the patient noted diarrhea and bowel movements that occurred 10 times a day. On the following day, his body temperature rose to over 39 degrees C. On the morning of the 17th day, he complained of severe pain in the right lower extremity. Swelling and erythema over his right lower leg were evident. The skin lesion spread rapidly over the knee and became necrotic. His right leg became increasingly swollen with the development of edema and hemorrhagic bullae. About 4 hrs after the emergence of the skin lesion, his blood pressure fell to less than 60 mmHg. Laboratory findings suggested disseminated intravascular coagulation and multiple organ failure due to serious bacterial infection. In spite of vigorous treatment including administration of antibiotics, dopamine, gabexate mesilate and plasma, he did not recover from the state of shock and died about 14 hrs after the appearance of leg pain. Bacterial culture of the blood and contents of the bullae grew a gram negative rod identified as Edwardsiella tarda (E. tarda). Histological findings showed necrotizing fasciitis. E. tarda has recently become recognized as a pathogenic bacteria, particularly in patients with an underlying illness. This is the first reported case of E. tarda septicemia with necrotizing fasciitis.

[Four cases of adult Listeria monocytogenes infection in the last 5 years--hepatic necrotic foci in the adult septic case].

We have reported on the clinical courses of 4 cases of adult Listeria monocytogenes (Lm) infection, and the autopsy findings of 2 cases, those we have observed over the past 5 years. They were 2 cases of meningitis, 1 case of meningitis and sepsis and 1 case of sepsis. These 4 cases had CML, neoplastic angioendotheliosis, SLE and post-renal transplant condition, as their underlying diseases, and all were receiving immunosuppressive therapy. One meningitis patient who recovered showed mild liver dysfunction during her clinical course. The other 3 patients who died had jaundice at the time of onset and severe liver dysfunction. The 2 cases those were autopsied were the sepsis cases. The one with an acute course and hepatic failure showed multiple miliary necrotic foci in the liver, where the presence of Lm in the cells could be verified. The other autopsy case, which had received adequate antibiotic therapy and the Lm infection had been cured, showed no necrotic foci in the liver. The case that had necrotic foci in the liver was the first such adult case in Japan. We have discussed the hepatic Lm infection in adult compromised hosts, which conventionally has not been considered a serious problem.