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Azaborines and ladder-type azaborines bearing various functional groups can be synthesized starting from common dibromo derivative intermediates, and among several substituents, the carbazol-9-yl group was shown to enhance the photo-luminescence quantum yield of the azaborines up to a value of unity.

Ladder-type pi-conjugated molecules bearing heteraborin (azaborine or thiaborin) units were synthesized, and X-ray crystallographic analysis of pentacene-type molecules showed that these molecules have rigid and planar structures. UV-visible spectroscopy and theoretical calculations revealed the enhancement of electronic interaction between heteraborin units, the decrease in HOMO-LUMO energy gaps, and the strong effect of the bridging main-group elements (nitrogen or sulfur) on the electronic states. The ladder-type molecules emitted strong fluorescence both in solution and in the solid state, and the emission-band shapes were different from each other, indicating the existence of intermolecular interactions in the solid state. Complex formation of the ladder molecules with fluoride ion was monitored by UV-visible spectroscopy, which revealed that the Lewis acidity of these molecules can be controlled by the elongation of pi systems and the change of the bridging main-group elements.

The phosphonium borane [p-Mes(2)B(C(6)H(4))PMePh(2)](+) complexes fluoride in water containing 10% methanol with a binding constant of 1.0(+/-0.1) x 10(3) M(-1) to afford the zwitterion p-Mes(2)FB(C(6)H(4))PMePh(2).

We retrospectively evaluated the frequency and identified the factors associated with the development of aortic stenosis (AS) in 96 patients with heterozygous familial hypercholesterolemia (FH). The frequency of AS was 31% (4/13) and that of critical stenosis was 15% (2/13) in older patients over the age of 70 years. All 4 patients with AS were female aged more than 70 years who were diagnosed with FH when aged more than 60 years. There were no significant differences in conventional coronary risk factors; however, the age at cardiac catheterization, age at diagnosis of FH and the cholesterol-years score (CYS) with AS were significantly higher than those without AS (p=0.006, p=0.017, p=0.021, respectively). In multiple regression analysis, CYS was a significant independent predictor for the development of AS (p=0.037) in 13 older patients over the age of 70 years. These results suggest that physicians should be aware that AS needs attention in older patients with heterozygous FH, especially women who have been diagnosed late in life and those who have been inadequately treated., 出版者照会後に全文公開

Plasma cholesteryl ester transfer protein (CETP) mediates CE/TG exchange among various lipoproteins. CETP deficiency results in low LDL and high HDL phenotype including apoE-rich large HDL. Large HDL could provide apoE to chylomicron/VLDL during lipolysis in post-prandial state, accelerating remnant lipoprotein uptake in the liver. To determine the effects of low CETP levels on post-prandial lipoprotein metabolism, lipid levels of plasma remnant-like lipoprotein particles (RLP) fraction were determined in one homozygous and three heterozygous CETP deficiency and controls with apoE3/3 phenotype. After oral fat-load, the area under curve (AUC) of TG levels were remarkably decreased in CETP deficiency as compared to controls (423+/-187 [S.D.] mg/dl x h in three heterozygous CETP deficiency and 926+/-268 [S.D.] in 10 controls, P=0.012). Similarly, the homozygote had a low AUC of TG levels (416 mg/dl x h). Plasma RLP-cholesterol levels were decreased in heterozygotes, but not significantly as compared to controls (P=0.14). HPLC analysis showed that increased RLP-cholesterol level was not due to conventional VLDL-LDL size RLP, but to those in large HDL size in the homozygote. In heterozygotes, bimodal distribution of RLP-cholesterol level was found in lipoprotein sizes of conventional VLDL-LDL and large HDL. Subjects with CETP deficiency appeared to have low levels of TG response and diminished remnant lipoprotein formation after fat-load.

CETP (cholesteryl ester transfer protein) and HL (hepatic lipase) play a role in the metabolism of plasma lipoproteins, but the effects of CETP and LIPC (gene encoding HL) genotypes on coronary atherosclerosis may be dependent on LDL (low-density lipoprotein)-receptor activity. Recently, the −1337 C>T polymorphism in the CETP gene has been reported in REGRESS (Regression Growth Evaluation Statin Study) to be a major determinant of promoter activity and plasma CETP concentration. In the present study, we have investigated the effects of the CETP promoter −1337 C>T and LIPC promoter −514 C>T polymorphisms on serum lipid profiles and risk of coronary atherosclerosis in 206 patients (154 males) with heterozygous FH (familial hypercholesterolaemia). To evaluate coronary atherosclerosis, we used CSI (coronary stenosis index) calculated from coronary angiograms. The CETP −1337 T allele was less frequent in subjects with a CSI ≥14 (mean value) in the group with coronary artery disease ( P =0.04, as determined by χ2 test). ANOVA revealed that HDL-C (high-density lipoprotein-cholesterol) and triacylglycerol (triglyceride) levels were not significantly higher in the presence of the CETP promoter −1337 T allele. Combined with LIPC promoter polymorphisms, HDL-C levels were highest and CSI were lowest with CETP −1337 CT+TT and LIPC −514 CC genotypes, but a significant interaction was not shown. A multiple logistic regression analysis revealed that, in patients with coronary atherosclerosis, the CETP − 1337 CC genotype was a significant genetic risk factor in FH (odds ratio=2.022; P =0.0256). These results indicate that the CETP promoter −1337C>T polymorphism is associated with the progression of coronary atherosclerosis in Japanese patients with FH, independent of HDL-C and triacylglycerol levels. Abbreviations: AP, angina pectoris; Apo, apolipoprotein; BMI, body mass index; CAD, coronary artery disease; CETP, cholesteryl ester transfer protein; CSI, coronary stenosis index; FH, familial hypercholesterolaemia; HDL, high-density lipoprotein; HDL-C, HDL-cholesterol; HL, hepatic lipase; IDL, intermediate-density lipoprotein; LDL, low-density lipoprotein; LDL-C, LDL-cholesterol; MI, myocardial infarction; NCBI, National Center for Biotechnology Information; REGRESS, Regression Growth Evaluation Statin Study

By Directive on RoHS, the use of six hazardous substances is restricted to new electrical and electronic equipment put on the market in Europe from 1 July 2006. The estimation of the type and the content of brominated flame retardants is necessary in plastics of the equipment and the parts. The new technique by using time-of-flight secondary ion mass spectrometry (TOF-SIMS) is proposed for rapid screening test of these substances. We named this technique one droplet extraction method. The sampling method of brominated flame retardants in plastic materials with toluene on silver substrate was investigated for analysis of trace organic compounds by TOF-SIMS. High impact polystyrene (PS) and polypropylene (PP) plates were prepared as evaluation samples containing decabromodiphenylether (DeBDE) of 0.01-10 wt%. Evaluation time that includes sample pretreatment time and measurement time was about 1 hour. The positive quasi-molecular ion (DeBDE+Ag)+ (DeBDE cationized with Ag) was suitable for estimation of DeBDE. It was proved that content and spectral intensity had the clear magnitude correlation within 0.01-10 wt% content of DeBDE. It was found that the quick decision of whether the brominated flame retardants in the plastics is the substance restricted or not by Directive on RoHS is possible by this method. We can screen the substances in wide range of content of 0.01-10 wt%. Also it was found that the quick decision of whether hexavalent chromium is present in metals is possible by an application of this method. It was confirmed that one droplet extraction method using TOF-SIMS is a very powerful technique for the rapid screening test of brominated flame retardants and Cr (VI). It can be expected that hazardous substance management that concerns Directive on RoHS becomes more reliable

[structure: see text] Ladder-type fused azaborines were synthesized. X-ray crystallographic analysis of a pentacene-type molecule shown here revealed the planarity of a fused azaborine. It was revealed by UV-vis and fluorescence spectra that such fused molecular structures are efficient for the extension of pi-conjugated systems containing main group elements.

To explore the possibility that raloxifene might influence an adipocyte differentiation and lipogenesis, we studied the effects of raloxifene on the expression of adiponectin and other peroxisome proliferator-activated receptor gamma targeting genes using the 3T3-L1 adipocytes. With standard adipogenic inducers, we added raloxifene at various doses for the adipocyte differentiation. Higher doses of raloxifene facilitated lipid accumulation of the 3T3-L1 cells. We next examined the differentiating and differentiated adipocytes and found that raloxifene augmented mRNA levels of adiponectin, adipocyte-specific fatty acid binding protein, and lipoprotein lipase dose-dependently in both. These effects were opposite those of 17beta-estradiol treatment. These findings suggest that raloxifene promotes adipocyte differentiation, providing a novel insight into the treatment of postmenopausal metabolic syndrome with hypoadiponectinemia.

Thermal decomposition of spin-coated films of partly protected polyvinylphenol with the t-butoxycalbonyl ( tBOC-PVP) group has been investigated by monitoring the intensity of the carbonyl stretching peak of the tBOC group by using temperature-variable time-resolved infrared spectroscopy (TR/IR). The temperature programming method has been used for determining the activation energy ( Ea) of the thermal decomposition. We compared the thermal decomposition behavior of tBOC-PVP films with that of the powders and the behavior of a 22% protected tBOC-PVP film with that of a 66% protected tBOC-PVP film. It was found that the Ea of the 22% protected tBOC-PVP film is distinctively higher than the others including the result given from thermogravimetric analysis (TG). In addition, the Ea of the 22% protected tBOC-PVP film increased up to 50 kcal/mol with the decrease of the remaining tBOC group, while the others were constant at 30 kcal/mol. Diglyme, which was used as the solvent in the 22% protected tBOC-PVP film, was residual after the temperature increased above 80 °C, and the reaction velocity of the tBOC group increased in accordance with the generation of the OH group. These results suggest that the OH group, which accelerates the thermal decomposition of tBOC-PVP, is hindered by the residual solvent in the case of the 22% protected tBOC-PVP films.

Lipoprotein lipase (LPL) deficiency is a rare autosomal recessive disorder caused by LPL gene mutation and is characterized by severe hyperchylomicronemia. Patients with LPL deficiency suffer from the frequent recurrence of acute pancreatitis, but the underlying mechanisms are not fully understood.A 22-yr-old male Japanese patient with severe hyperchylomicronemia was admitted to our hospital in 1973. He had no consanguinity and no family history of hyperlipidemia. He was genetically diagnosed as LPL deficiency (homozygous for LPL(Arita)) with no LPL mass or activity in postheparin plasma. He has experienced recurrent acute pancreatitis 22 times during our 31-yr clinical follow-up, but no pancreatic pseudocyst, irregularity of the pancreatic duct, or abnormal pancreatic calcification was observed in computed tomography. Moreover, his pancreatic endocrine function, as assessed by the oral glucose tolerance test, has preserved more than 30 yr. Although he was a current smoker, no clinically significant atherosclerotic lesion had been observed.From the long-term observation of this patient, we propose that LPL deficiency is not invariably associated with high mortality and that even with repeated episodes of acute pancreatitis, pancreatic function may be slow to decline.

1-Hydro-6-carbaphosphatrane 2 was obtained as a mixture with its tautomer, 3. Tautomers 2 and 3 were isolated by the recrystallization from different solvents, respectively, and each structure was determined by X-ray crystallographic analysis. Variable-temperature NMR experiments revealed that pentacoordinate 2 and tricoordinate 3 are under the equilibrium, showing that 3 is more stable. The theoretical calculations found a weaker transannular PC bond in 2 than in 1-hydro-5-carbaphosphatrane, 1, which can be considered to be the reason 1-hydro-6-carba-phosphatrane 2 is less stable than its tautomer 3.

A 38-year-old Japanese woman was admitted to hospital for further examination of systemic xanthomas. She had a past history of genital bleeding during her third delivery at the age of 21 years. She was diagnosed with Sheehan's syndrome. Her serum total cholesterol and triglyceride concentrations were 500 and 898 mg/dl, respectively. She was also diagnosed as having type III hyperlipoproteinemia on the basis of the presence of a broad-beta-band on agarose gel electrophoresis and extremely high concentrations of very-low-density lipoprotein cholesterol (310 mg/dl). The diagnosis was later confirmed by her apolipoprotein E isoforms (E2/E2) and genotypes (epsilon2/epsilon2). Thyroid and corticosteroid hormone replacement therapy cured the xanthomas, but also elevated her blood pressure. The serum concentration of intermediate-density lipoprotein cholesterol was consistently high, whereas that of low-density lipoprotein cholesterol was relatively low during the follow-up. Coronary atherosclerosis had already developed by the age of 38 years, and progressed significantly over the following 28 years. Severe stenotic lesions were observed in the bilateral renal arteries and carotid arteries, and in the abdominal aorta when she was 66 years old. These findings suggest that the continuous elevation of intermediate-density lipoprotein cholesterol for a long period contributed to the development of the atherosclerotic lesions.

Novel 9-phosphatriptycenes were synthesized by utilizing ortho-lithiation of a triarylphosphine oxide as a key step. The structural analysis of the 9-phosphatriptycene oxide revealed its highly distorted structure around the phosphorus atom, which is consistent with the up-field shift in the 31P NMR spectrum. The 9-phosphatriptycene and its chalcogenides were synthesized by ordinary methods, and the spectral comparisons of these chalcogenides indicated the large s-character of the lone-pair orbital or the phosphorus–chalcogen σ bonds of those species. The 9-phosphatriptycene oxide was reacted with lithium naphthalenide to give the ring-opened products. © 2004 Wiley Periodicals, Inc. Heteroatom Chem 15:437–446, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20038

1-Aquo- and 1-ethyloxonio-5-carbasilatranes 2 and 3 were synthesized. X-ray crystallographic analysis revealed that 2 has a nearly ideal trigonal bipyramidal structure, in which the water molecule is located at the apical position. This water molecule is exchangeable with the other Lewis bases, such as H218O and HMPA. Theoretical calculations suggested that 2 would acquire the stabilization energy (20 kcal mol-1) by complexation. Deprotonation of 2 by pyridine and not by m-nitroaniline showed that the pKa value is smaller than that of free water, and that the water molecule is activated by complexation.

A novel synthetic route to a 9-phosphatriptycene was developed by utilizing ortho-lithiation of a triarylphosphine oxide as a key step. Systematic comparisons of the NMR spectra of 9-phosphatriptycene derivatives indicated the large s character of the lone pair orbital or the phosphorus–chalcogen bonds of the 9-phosphatriptycene derivatives.

Basal cell nevus syndrome (BNS syndrome) is considered to be an autosomal dominant hereditary disease, associated with pits of the palm, multiple jaw cysts, calcification of the falx cerebri, and skeletal anomalies.We treated two sisters with BNS syndrome associated with multiple jaw cysts. In their grandmother and other brother and sister, multiple jaw cysts were recognized. It was suggested that genetic factors might play a role in the development of multiple jaw cysts. Moreover, two of six children of the family also had ocular hypertelorism and pits of the palm.

Design: Cross-sectional study of fasting serum lipid and lipoprotein levels, pre-heparin lipoprotein lipase (LPL) mass, several other metabolic parameters, and intra-abdominal fat areas in 26 Japanese poorly controlled type 2 diabetic men and 23 women when matched for age, body mass index (BMI), and HbA 1c between genders. Subjects: Study subjects were Japanese type 2 diabetic patients who were admitted to our hospital between Jun 2001 and Aug 2002 because of their poorly controlled diabetes. A total of 49 subjects [40–79 years of age, average age 61.5±8.7; mean BMI 23.2±3.7 kg/m 2 ] with fasting plasma glucose (PG) and HbA 1c levels being 251±76.5 mg/dl and 10.8±2.2%, respectively, were involved in this study. Methods: Pre-heparin LPL mass was determined by enzyme linked immunosorbent assay. Remnant like particle cholesterol (RLP-C) level was measured using an immunoaffinity mixed gel containing anti-apolipoprotein (apo) A-I and anti-apo B monoclonal antibodies. Serum leptin level was determined by radioimmunoassay. Intra-abdominal fat area was determined by computerized tomography analysis at the umbilical level. Results: The men group showed a higher serum triglycerides (TG) and RLP-C levels, and lower high density lipoprotein–cholesterol levels and pre-heparin plasma LPL mass than did women. Serum leptin level was higher in women than in men counterparts. The intra-abdominal subcutaneous fat areas were significantly larger in women than in men counterparts, whereas the visceral fat areas did not differ. Conclusion: In Japanese population, poorly controlled type 2 diabetic men had more unfavorable lipid profile than did women counterparts, which may be associated with decreased lipolysis of plasma TG-rich lipoproteins by LPL.

Background: C-reactive protein (CRP) is a well-established, sensitive marker of systemic inflammation and the risk of cardiovascular disease. High-density lipoprotein (HDL) is an anti-atherogenic lipoprotein known to be regulated by genetic and acquired factors. Methods: The patient was a 77-year-old Japanese woman, who was diagnosed with type 2 diabetes mellitus (DM), with a body height of 152 cm and a weight of 65 kg (body mass index 28.1 kg/m2). She suffered from diabetic foot gangrene in her right foot with high-grade fever when she visited our hospital. Her plasma glucose (PG) concentration and serum CRP were markedly elevated being 21.6 mmol/l and 370 mg/l, respectively, while her serum HDL-C concentrations were markedly low being 0.13 mmol/l. She was immediately admitted to our hospital and received intensive insulin treatment, along with intravenous-administration of antibiotics. Her general conditions were gradually improved and the high-grade fever disappeared, with concentrations of plasma PG and serum CRP being reduced, and concurrent reciprocal increase in her serum HDL-C concentrations. Results: To determine the potential causative factors responsible for the drastic change in serum HDL-C concentrations, we investigated the relationship of serum HDL-C to serum CRP, serum total protein (TP) and PG. Serum CRP and PG showed inverse relationships with serum HDL-C, while serum TP concentrations showed a positive association with HDL-C. After multivariate analyses with CRP, TP and PG as independent variables and serum HDL-C as dependent variable, CRP maintained its independent association with serum HDL-C. CRP also showed inverse correlations with lipoprotein lipase (LPL) mass and cholesteryl ester transfer protein mass. Conclusions: In acute inflammation and poorly controlled diabetes, CRP is suggested to be inversely associated with serum HDL-C, independent of PG and TP.

Synovial chondromatosis of the temporomandibular joint is a rare disease, and extra-articular synovial condromatosis of the temporomandibular joint is even rarer. A review of the English literature from 1980 to 2000 has revealed 51 cases of synovial chondromatosis affecting the temporomandibular joint. We report a case of extra-articular synovial condromatosis, for which we carried out a long-term follow-up of the postoperative course using diagnostic images.

OBJECTIVE: To assess whether serum lipoprotein(a) is a risk factor for diabetic retinopathy in the elderly. DESIGN: A cross-sectional study. SETTING: Outpatient diabetic clinic. PATIENTS: One hundred four noninsulin-dependent diabetic patients (35 males, 69 females). Twenty-three were less than 60 years of age (middle-aged), and 81 were 60 years or older (elderly). MEASUREMENT: Levels of lipoprotein(a) (Lp(a)) and lipids were measured in fasting serum. HbA1c was also measured as an indicator of diabetic control. Other indicators possibly related to retinopathy were also checked. Retinopathy was estimated by photographs of fundi. RESULTS: Significantly higher indicators in the group with retinopathy than in the group without were: HbA1c, Lp(a), duration of diabetes, and systolic blood pressure (BP) in the total cases; HbA1c, duration of diabetes, and Lp(a) in the middle-aged; HbA1c, systolic BP, and Lp(a) in the elderly. Multiple logistic regression analysis showed that only HbA1c and Lp(a) were independent risk factors for retinopathy in all cases and in the elderly. The incidence of retinopathy was positively correlated to serum Lp(a) levels. CONCLUSION: Lp(a) is an independent risk factor for diabetic retinopathy.

The subject was a 26-year-old Japanese woman of 148 cm height, 96.2 kg of body weight (BW) (body mass index (BMI) of 43.8 kg/m(2)). She was referred to our hospital on May 1, 2000 for the evaluation of marked hyperglycemia with clinical symptom of general malaise, polydipsia, and ketonuria (3+). She did not smoke, or drink alcohol. But, she tended to eat lots of sweet food every day before the onset of this symptom. Her father was diagnosed type 2 diabetes mellitus. Her fasting plasma glucose and HbA(1c), and serum C-peptide were 398 mg/dl, 7.8% and less than 0.05 ng/ml [normal range: 0.94-2.8], respectively. She tested negative for anti-glutamic acid decarboxylase (GAD) antibodies and islet-cell antibodies. C-peptide level in her urine was as low as 3.4 microg/day. We immediately started insulin treatment under the diagnosis of abrupt onset of diabetes mellitus with diabetic ketoacidosis on the day of her admission, and the insulin treatment was continued after her being discharged. She showed continuous BW reduction until her BW reached approximately 60 kg, followed by her BW being plateau. During the period, intra-abdominal visceral fat (VF) and subcutaneous fat (SF) volume assessed by helical computerized tomography (CT) showed a substantial reduction [3.9-0.5 l for VF, 19-3.2 l for SF volume]. Pre-heparin plasma lipoprotein lipase (LPL) mass showed a considerably lower value when she had continuous BW reduction than did it when her BW reduction discontinued. These findings suggest that in this subject, continuous BW reduction after the abrupt onset of diabetes is closely associated with intra-abdominal fat mass reduction, which may be related to decreased production of LPL.

Background: Single low-density lipoprotein (LDL)-apheresis may affect serum remnant-like particle-cholesterol (RLP-C), C-reactive protein (CRP) and malondialdehyde-modified (MDA)-LDL concentrations. Subjects and methods: Six subjects with hypercholesterolemia (five men, one woman) were involved in this study. Mean age and body mass index of the study subjects were 58±3.1 years and 23.6±2.07 kg/m2, respectively. Five of the subjects were diagnosed as heterozygous familial hypercholesterolemia (FH) because of having both marked hypercholesterolemia and Achilles tendon xanthomas. LDL apheresis was introduced and continued using a dextran sulfate cellulose adsorption column technique every 2 weeks. Serum RLP-C was measured using an immunoaffinity mixed gel containing anti-apolipoprotein A-I and anti-apolipoprotein B monoclonal antibody. Serum CRP was measured by latex-enhanced assay. Serum MDA-LDL was measured using monoclonal antibody against MDA-LDL (ML25). Results: Combined treatment in the steady state pre-treatment yielded a total, LDL- and HDL-cholesterol, and TG concentrations of 5.39±0.81, 3.82±1.03, 1.24±0.29 and 0.92±0.43 mmol/l, respectively, and a post-treatment total, LDL- and HDL-cholesterol and TG concentrations of 2.79±0.37 (−48%, p

We have previously reported a potent and specific cholesteryl ester transfer protein (CETP) inhibitor JTT-705 was a potentially anti-atherogenic compound (Nature 406 (2000) 203). In the present study, we investigated in vitro how this compound affects properties of high density lipoprotein (HDL) in Japanese white (JW) rabbits in terms of reverse cholesterol transport in J774 macrophages. Plasma HDL-cholesterol (C) level was significantly higher in the rabbits administered JTT-705 than in control rabbits on days 3 and 7. Both HDL 2 and HDL 3 -C levels were also significantly higher in JTT-705-administered rabbits than in control rabbits. During this period, plasma CETP activity was kept lower in JTT-705-administered rabbits than in controls. To determine how this compound affects the property of HDL particles, we investigated the C efflux induced by HDL from JTT-705-administered and control rabbits in J774 macrophages. Cholesterol ester (CE) concentration in J774 macrophages was reduced in proportion with increasing concentration of the added HDL to the culture media for J774 macrophages in both groups, suggesting that the HDL from JTT-705-administered rabbits was able to reduce CE concentration in J774 macrophages as efficiently as that from control rabbits. This result, together with the finding that the absolute HDL concentration increased in JW rabbits administered this CETP inhibitor, suggests that treatment with this new compound causes a beneficial effect on lipid metabolism in terms of anti-atherogenicity.

1-Hydro-5-carbaphosphatrane (1) and 1-methyl-5-carbaphosphatrane (2), the first 5-carbon analogues of phosphatranes, were synthesized by a demethylation reaction of cyclic phosphinate 3. X-ray analysis revealed that 1 has a typical trigonal bipyramidal structure with hydrogen and carbon atoms at the apical position and three oxygen atoms at the equatorial positions, indicating that 1 is a phosphorane in the perfectly "anti-apicophilic" arrangement. Apical P-C and P-H bond lengths were 1.921(2) and 1.38(2) A, respectively. The (1)J(PH) value of 1 and the (1)J(PC)(P-CH(3)) value of 2 were 852 and 215 Hz, respectively, which are extraordinarily large for the apical coupling constants of phosphoranes, but close to those of the reported phosphatranes with a 5-nitrogen atom. IR and Raman spectra are also reported. Force constant calculations indicate the transannular bond in carbaphosphatrane is 3 times stronger than in silatrane, due to its covalent character.

High density lipoprotein-cholesterol (HDL-C) levels are inversely related to the incidence of coronary artery disease. We studied the influence of a G(-75)--A transition in the promoter of the apolipoprotein (apo) A-I gene, a major protein component of HDL, on serum HDL-C levels in hyperlipidemic subjects. Seventy three hyperlipidemic subjects with serum levels of high HDL-C (HDL-Cor = 70 mg/dl, Group H) were compared with hyperlipidemic subjects with levels of HDL-C between 40 and 70 mg/dl (Group N) and those with HDL-C40 mg/dl (Group L). Group H showed a higher incidence (45.2%) of low plasma cholesteryl ester transfer protein (CETP) activity than Groups N (9.1%) and L (5.3%) (p0.001). Group H had a higher incidence of the G(-75)--A transition (0.275) than Groups N (0.117, p0.05) and L (0.056, p0.01), among subjects with normal CETP activities. The HDL-C levels in subjects with the transition (84 +/- 16 mg/dl) were higher than those in subjects without the transition (56 +/- 12 mg/dl) (p0.05). These data suggest that a G(-75)--A transition of the apo A-I gene promoter, in addition to the common mutation of CETP gene, contributes to high HDL-C levels among hyperlipidemic patients in Japan.

Tetanus is a fatal disease if early treatment is not appropriately performed. Numerous patients complaining of trismus consult dentists or oral surgeons. Trismus frequently occurs as an initial sign of tetanus. Tetanus should therefore always be taken into consideration when examining patients with trismus.A 62-year-old female was referred to our clinic by a physician because of trismus and shoulder stiffness. However, trismus and spasms of the jaw, neck and shoulder musclature were rapidly aggravated. Although Clostridium tetani was not detected, clinical symptoms such as severe trismus and facial grimacing were strongly suggestive of tetanus.The patient was treated by a prophylactic tracheotomy, tetanus antitoxin and high dose antibiotics therapy. The clinical course of the patient improved without convulsions.

OBJECTIVE To determine how lipoprotein lipase mass in the pre-heparin plasma is affected by body fat distribution, which is known to be closely related to lipid disorder, either directly or through insulin resistance. SUBJECTS A total of 57 subjects consisting of 50 hyperlipidemic and 7 normolipidemic subjects (age 54 +/- IIy; 31 men, 26 women; body mass index 24+/- 2.5 kg/m2; serum total cholesterol 6.4+/-1.5 mmol/l; triglycerides, 2.4 +/- 1.7 mmol/l; HDL-cholesterol 1.3 +/- 0.5 mmol/l) were enrolled. MEASUREMENTS We investigated the correlation between pre-heparin plasma LPL mass and intra-abdominal visceral fat area (or subcutaneous fat area) evaluated by computed tomography, and serum lipids and lipoproteins. RESULTS Pre-heparin plasma LPL mass correlated inversely against intra-abdominal visceral fat area (r = - 0.51, p < 0.0001) and body mass index (r = - 0.46, p = 0.0003), but did not show any significant correlation with subcutaneous fat area. Pre-heparin plasma LPL mass had a positive correlation with serum high density lipoprotein cholesterol (r = 0.45, p = 0.0004) and a negative correlation against serum triglycerides (r = - 0.48, p = 0.0002). CONCLUSIONS Pre-heparin plasma LPL mass is closely associated with intra-abdominal fat distribution, and the measurement of its value gives useful information concerning metabolic disorder.

Transient global ischemia causes neurogenesis in the dentate gyrus of adult rodents. Ischemic insults to rodents also induce cyclooxygenase-2 (COX-2), an isoform of cyclooxygenases (COXs) and a rate-limiting enzyme for prostanoid synthesis. In the present experiments, adult Mongolian gerbils were chronically treated with acetylsalicylic acid (ASA), a non-selective COX inhibitor, and the proliferation of cells in the dentate gyrus was examined under ischemia. It was proved that BrdU-labeled cells in the dentate gyrus were significantly reduced in number following ASA treatment after 10 min global ischemia. The result strongly suggests that COX, probably COX-2, and prostanoids play an important role in the proliferation of neural cells after ischemia in gerbils.

In this study, we analyzed plasma lipid and lipoprotein levels before and after treatment with 1-desamino-8-D-arginine vasopressin (DDAVP) in subjects with partial and complete central diabetes insipidus (DI) in order to determine how a shortage and supplement of this hormone affect plasma lipid metabolism. The subjects consisted of 6 patients with partial and 6 with complete central DI. After treatment with DDAVP through nasal cavity, plasma total cholesterol (TC) level did not decrease either in complete or partial form. Plasma triglyceride (TG) levels decreased from 306+/-175 mg/dl to 198+/-91 (35% decrease, p=0.027) in complete form, while TG did not change significantly in partial form. A detailed investigation of plasma lipoprotein metabolism during treatment with DDAVP was carried out in 3 of the 6 subjects with complete form of DI. Lipoprotein lipase activity and mass in post-heparin plasma from those three subjects tended to increase after treatment with DDAVP, along with the complete disappearance of an unusual lipoprotein between low density lipoprotein (LDL) and very low density lipoprotein (VLDL) as analyzed by polyacrylamide gel electrophoresis. These results suggest that the DDAVP treatment has a favorable effect on lipid and lipoprotein metabolism, especially triglyceride-rich lipoproteins, either directly or through modifying factors contributing to lipid metabolism.

A fluorescent host molecule bearing a bicyclic triarylphosphate framework was synthesized. Its inclusion behavior to C60 was revealed by fluorescent titration. Cocrystallization of the host and C60...

Postprandial hyperlipidemia is frequently accompanied with intra-abdominal visceral accumulation in human subjects. We have found that the decreased lipoprotein lipase (LPL) mass and activity is negatively associated with the amount of visceral fat accumulation. Here, we studied the postprandial hyperlipidemia using the OLETF rat, a model with visceral obesity, in order to clarify the molecular mechanism causing postprandial hyperlipidemia accompanied with visceral obesity. At the same age of 32 weeks, the OLETF rats showed obviously higher plasma leptin, total cholesterol, triglyceride, and HDL-cholesterol levels than the control LETO rats, although the plasma glucose level was not significantly different. Fat-loading test revealed the delayed metabolism of exogenous fat in the OLETF rats compared to the LETO rats, similar to human subjects with visceral obesity. In the obese rats, plasma levels of LPL mass and activities were 60 and 49% of control rats. The expression of LPL gene was decreased in subcutaneous adipose tissues and skeletal muscle of OLETF rats to 40 and 52% compared to those of LETO rats. In OLETF rats, plasma tumor necrosis factor-alpha (TNF-alpha) and insulin levels were increased to 2.0- and 2.3-folds compared to those in control rats. Furthermore, plasma insulin and TNF-alpha levels in OLETF rats were negatively correlated with the expression levels of LPL gene in subcutaneous fat and muscle. These results indicate that decreased LPL mass and activity in the animal model with visceral obesity is possibly caused by decreased expression of LPL gene in tissues mediated by the increased levels of insulin and TNF-alpha. The different expression of LPL gene in tissues associated with the increased levels of insulin and TNF-alpha possibly elucidate the underlying mechanisms involving the postprandial hyperlipidemia observed in visceral obesity.

A 61-year-old Japanese woman with heterozygous familial hypercholesterolemia (FH), type 2 diabetes mellitus and coronary artery disease underwent coronary artery bypass grafting (CABG) utilizing a saphenous vein graft at the age of 46, in June 1984, 6 months before low density lipoprotein (LDL) apheresis was started. She had received LDL apheresis every two weeks, along with combined drug treatment since the age of 47 (December 1984). She had bilateral xanthelasma and Achilles tendon xanthomas. Her fasting baseline serum total cholesterol and triglyceride level were 464 mg/dl and 57 mg/dl, respectively at the age of 47 when she visited our hospital for the first time. Analysis of the genomic DNA from the patient revealed heterozygous amino acid substitution of Leu for Pro664 in the LDL receptor gene. She was diagnosed as type 2 diabetes mellitus at the age of 53. Combined treatment in the steady state yielded a pretreatment LDL cholesterol level of 230+/-14 mg/dl and a posttreatment level of 57+/-7.6. All grafts were widely patent after as long as 14 years since CABG, suggesting that LDL apheresis combined with drug therapy is highly effective in preventing the occlusion of bypass grafts in a patient with heterozygous FH and type 2 diabetes mellitus.

An involvement of the low density lipoprotein receptor (LDLR) gene family in both intracellular signal pathways for neural organization and metabolic pathways for lipoprotein homeostasis is now well established. The discovery of LR11, a mosaic LDLR family member offers the opportunity to gain new insights into receptor multifunctionality. Here, we studied the proliferation-dependent expression of LR11 mRNA and protein using two cultured cell lines, IMR32 neuroblastoma and PC12 pheochromocytoma. Within 24 h, the LR11 protein rose 1.9-fold in proliferating IMR32 cells, and increased further to 5.3-fold at 72 h. This conformed with a transcript level increase of 4.7-fold at 72 h in the proliferating cells. On the other hand, under differentiation conditions, a 2.9-fold increase was observed within 24 h, but at 72 h thereafter the protein levels decreased to 60% of control. The transcript also increased to 1. 8-fold within 24 h, and then decreased to 1.1-fold at 72 h. In order to assess the transcriptional activities of the LR11 gene, we identified the 5'-flanking region of the murine LR11 gene. Transfection of IMR32 and PC12 cells with plasmids containing the whole or deleted fragments of 5'-flanking region showed that element(s) responsible for the above described different transcriptional activities are located in the upstream sequence between -861 and -396. Thus, the transcription of LR11 in these two cell systems is regulated differently during proliferation and differentiation, suggesting that the multifunctionality of LR11, as well as other LDLR family members, for rapid cell growth in malignant cells and neural outgrowth in cultured neurons, respectively. The possible involvement of LR11 in cellular proliferation and differentiation sheds new light on its functions in neurons, malignant, and vascular cells.

The patient was a 39-year-old Japanese male with a body height of 160 cm and weight of 48 kg who was diagnosed as Werner syndrome of homozygote for mutation 4. His plasma total cholesterol (TC), triglycerides (TGs), high density lipoprotein-cholesterol (HDL-C) and apolipoprotein A-I (apo A-I) levels were 7.2, 2.1, 1 mmol/l and 128 mg/dl, respectively. During the clinical course of treatment of this patient, his plasma levels of HDL-C and apo A-I declined drastically to levels of as low as 0.2 mmol/l and 10 mg/dl, respectively, with concurrent reciprocal increase in plasma TG levels. Plasma HDL-C, apo A-I and TG levels gradually returned to original values. Lipoprotein lipase activity and mass in post-heparin plasma were markedly low when the apo A-I and HDL-C levels decreased to 10 mg/dl and 0.21 mmol/l, respectively, and these values improved when the apo A-I and HDL-C levels returned to more normal values of 106 mg/dl and 0.94 mmol/l, respectively. The result of direct sequence of the exon 3 and 4, and the promoter region of the apo A-I gene of the patient revealed no single nucleotide changes. These results suggest that in the present patient, impaired hydrolysis of TGs in TG-rich lipoproteins, is due at least in part to a decreased LPL enzyme level, reduced the formation of nascent HDL, resulting in unusually low plasma levels of HDL-C and apo A-I.

An intramolecular sila-Friedel-Crafts reaction was developed and applied to the synthesis of dibenzosilole derivatives. This reaction proceeds under mild conditions to afford the target in relatively high yield, indicating its availability as a versatile synthetic method. The synthesis of trisilasumanene, a silicon analogue of sumanene, was achieved using the present reaction.

A new heterozygous lipoprotein lipase gene defect has been identified in a type I hyperlipidemic patient at the position of notable amino acid Asn 291. The patient is a 33-year-old male. His body mass index (BMI) was 18.5 kg/m2. The total cholesterol (TC), triglycerides (TG) and high density lipoprotein-cholesterol (HDL-C) concentration from his fasting plasma were 4.8, 11.9 and 0.4 mmol/l, respectively. The lipoprotein lipase (LPL) activity and mass in the postheparin plasma (PHP) from the patient were 0.58 mmol/ml/h (normal range: 7.7±2.6) and 244 ng/ml (normal range: 192±30), respectively. The hepatic lipase activity of the PHP from the patient was 10.6 mmol/ml/h (normal range: 9.9±3.6). DNA analysis of the LPL gene revealed that this patient had a heterozygous one nucleotide deletion of A coding Asn 291, resulting in a premature termination of the LPL protein at amino acid residue 303. The other abnormality in the LPL gene of the proband was an amino acid residue 194 defect (Ile194→Thr), which is known to cause a defective enzyme. A medium-chain triglyceride (MCT) loading test was conducted to find how this triglyceride affects plasma lipoprotein metabolism in this patient in a short term ( Fig. 3 ). The plasma total cholesterol (TC) or high density lipoprotein (HDL)-C levels did not change significantly after oral administration of a fatty meal containing long chain triglycerides (LCT) or MCT. The plasma TG level, on the other hand, increased from 11.9 to 19.2 mmol/l (+61%) at 6 h after loading a fatty meal containing LCT, whereas the plasma TG levels tended to even decrease at 6 h after oral administration of an MCT, tricaprin (from 11.6 to 10.5 mmol/l (−9.4%)). These results suggest that MCT, as opposed to LCT, is useful for treatment of type I hyperlipidemia with a novel mutation at the notable amino acid Asn 291 of the LPL gene.

Rh complexes 5 and 6 were synthesized via the titled carbine 1 . In the IR spectrum of 6 , the carbonyl stretching frequency was observed at the lower wave number among all [(carbene)Rh(CO) 2 Cl] complxes reported to date, including the highest electron-donating ability of carbene 1 .

Recently, close attention has been given to the relationships between plasma adiponectin levels and lipolytic enzymes such as hepatic lipase and lipoprotein lipase activities in an effort to understand the possible mechanism of hyperlipidemia in low adiponectin. The cross-sectional study by Schneider et al. (1) has concluded that postheparin plasma hepatic lipase activity is inversely associated with plasma …

We present a case of a 43-year-old Japanese man with heterozygous familial hypercholesterolemia (FH) with severely elevated serum triglycerides (TG). He drank large quantities of alcohol but had no endocrinological disorder or diabetes mellitus. He had a recurrent, acute pancreatitis. His fasting serum total cholesterol (TC), TG, and HDL-C levels and an apolipoprotein E genotype of E3/E3 suggested a diagnosis of type V hyperlipidemia. Yet, the patient had bilateral Achilles tendinous xanthomata, which prompted us to conduct a gene analysis for the LDL receptor, and this revealed the heterozygous form of the 317 cysteine to serine mutation, demonstrating that this was a case of FH. We recommend that physicians consider the existence of FH, even in hyperlipidemic subjects with lipid profiles far from those typical of FH, whenever a patient has tendinous xanthomata.