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Background: Dental caries (DC) are more prevalent in individuals with diabetes than in healthy individuals. However, the association between glycaemic control and DC has not been well characterized in patients with type 2 diabetes mellitus (T2DM). We therefore assessed the association between glycated haemoglobin (HbA1c) serum concentrations and the prevalence of DC in patients with T2DM., Methods: Retrospective analyses of data pertaining to 108 Japanese patients with T2DM hospitalized because of poor or worsened glycaemic control were included. We divided the patients based on HbA1c into two groups: HbA1c level ≥75 mmol/mol (9.0%) as poorly controlled T2DM, and HbA1c level <75 mmol/mol (9.0%) as a control group. We compared the association of lifestyle factors, dental caries, and periodontal health between patients with poorly controlled T2DM and controls. Stepwise multiple regression analyses were performed to evaluate the association between HbA1c, the absolute number of decayed teeth (DT), the sum of decayed, missing, and filled teeth, and the Met Need Index (MNI)., Results: DT was higher and MNI was lower in patients with poorly controlled T2DM as compared to that in controls (P = 0.006 and P = 0.004, respectively). Multiple regression analyses revealed a significant association between HbA1c levels and DT (adjusted β = 0.039, 95% confidence interval [CI], 0.005 to 0.072, P = 0.025) and the MNI (adjusted β = -0.216, 95% CI -0.374 to -0.058, P = 0.008)., Conclusions: DT and MNI were associated with HbA1c in T2DM patients.

Aim: The aims of this study were to determine whether the serum levels of precursor brain-derived neurotrophic factor (proBDNF), mature BDNF (mBDNF), and matrix metalloproteinase-9 (MMP-9) are altered in patients with eating disorders (ED), including anorexia nervosa (AN) and bulimia nervosa (BN), and to explore whether those levels are associated with decision-making abilities., Methods: Nineteen women with AN, 28 women with BN, and 22 age-matched healthy control women (HC) were enrolled in the current study. All participants had their decision-making abilities assessed using the Iowa Gambling Task (IGT). Their eating-related pathophysiology and depressive/anxiety symptoms were also evaluated., Results: The MMP-9 level in AN was significantly lower than that in either BN or HC, but the serum levels of proBDNF and mBDNF did not differ among the three groups. Investigation of the serum levels of proBDNF and MMP-9 in patients with ED and controls revealed a significant correlation between them. In the BN, there were positive correlations between mBDNF level and IGT performance and also between MMP-9 level and IGT performance, but these correlations did not occur in AN. The MMP-9 level was positively associated with the Symptom Scale, one of the subscales of the Bulimic Investigatory Test, Edinburgh, only in AN., Conclusion: These results suggest that the serum level of MMP-9 plays a role in the pathophysiology of AN, and both the serum levels of mBDNF and MMP-9 may be associated with decision-making abilities in patients with BN., (© 2016 The Authors. Psychiatry and Clinical Neurosciences © 2016 Japanese Society of Psychiatry and Neurology.)

BACKGROUND Richter's obturator hernia is a rare abdominal hernia that is difficult to diagnose. The purpose of this case report is to show an unusual presentation of a fatal Richter's obturator hernia that was accompanied by a femoral abscess. CASE REPORT An 89-year-old woman complained of sudden left coxalgia and a gait disorder but no abdominal symptoms. She had no history of trauma or surgery in the inguinal area. Twenty-three days after her first complaint of coxalgia, the patient was admitted in a coma with necrotizing fasciitis in the left inguinal area. The patient died of asystole due to hyperkalemia. During surveillance for the cause of death, a Richter's type of incarcerated obturator hernia was identified at autopsy. The incarcerated small intestine had penetrated into the left obturator foramen to form an abscess that extended into the deep femoral region. CONCLUSIONS Obturator hernia accompanied by femoral abscess is extremely rare, but it should be suspected when a patient with no history of trauma or surgery has a femoral abscess, even in the absence of abdominal symptoms., Competing Interests: Conflicts of Interest: None declared

Background: Decision-making is reported to be impaired in anorexia nervosa (AN) and bulimia nervosa (BN), but the influence of mood status, pathophysiological eating, and weight concerns on the performance of decision-making ability between AN and BN is still unclear. The aims of this study were to investigate differential impairments in the decision-making process between AN, BN, and healthy controls (HC), and secondly, to explore the role of mood status, such as anxiety, depression, pathological eating, and weight concerns, in decision-making ability., Methods: Patients suffering from AN (n = 22), BN (n = 36) and age-matched HC (n = 51) were assessed for their decision-making abilities using the Iowa Gambling Task (IGT). Self-reported questionnaires including the Eating Disorder Examination Questionnaire (EDE-Q), the Bulimia Investigatory Test, Edinburgh (BITE), the Eating Disorders Inventory, the Maudsley Obsessive-Compulsive Inventory measuring obsessive-compulsive traits, the Hospital Anxiety and Depression Scale, and the Toronto Alexithymia Scale were used to assess pathological eating concerns and attitude to feelings., Results: Significant differences in IGT performance were observed between BN and HC. Significant negative correlation was found between IGT performance and the BITE symptom subscale in AN. In BN, there was a negative correlation between the EDE-Q weight concerns subscale and IGT performance. It was also found that increased anxiety, depression, and eating/weight concerns predicted poorer decision-making., Conclusion: Different patterns of association between pathological eating concerns/behaviors and performances in decision-making ability were found between AN, BN, and HC. Anxiety, depressive mood status, and eating/weight concerns were related to decision-making ability.

Aims: To clarify the usefulness of protein-sparing modified formula diet in obese type 2 diabetic patients, the effects of partial use of formula diet on weight reduction and changes in related metabolic variables, and the improving rates of risk factors per 1% body weight reduction, were compared with those of conventional subcaloric diet., Subjects and Methods: Obese patients [BMI >25 kg/m²] with diabetic mellitus were randomly assigned to a low-caloric diet with partial use of formula diet group (FD, n = 119) and a conventional low-caloric diet group (CD, n = 110). Subjects in FD took one pack of formula diet (MicroDiet®, 240 kcal/pack) in place of one of three daily low-caloric meals for 24 weeks. Total daily calorie prescribed was same., Result: Weight reduction was greater in FD than in CD (week 24: -3.5 vs -1.4 kg; all p < 0.001). Systolic blood pressure decreased significantly only in FD. HbA1c reduction was greater in FD than in CD. HDL-cholesterol increased significantly more in FD than in CD (week 24: +2.8 vs. +0.6 mg/dl, p < 0.001). Among several improving rates (%) of risk factors/1% body weight reduction, those of HbA1c at weeks 16 and 24, triglyceride at week 8 and HDL-cholesterol at week 24, were significantly higher in FD than CD. Doses of sulfonylurea and thiazolidinedione were significantly decreased in FD than in CD., Conclusion: Partial use of formula diet was much more effective in reducing body weight, and also in improving coronary risk factors than conventional diet in part due to reduced body weight through decreased energy diet intake and due to dietary composition of the formula diet., (© 2013 Asian Oceanian Association for the Study of Obesity . Published by Elsevier Ltd. All rights reserved.)

Cys116, Lys240*, and Asp241* (asterisks indicate residues from the second subunit of the active dimer) at the active site of L-methionine γ-lyase of Pseudomonas putida (MGL&#95;Pp) are highly conserved among heterologous MGLs. In a previous study, we found that substitution of Cys116 for His led to a drastic increase in activity toward L-cysteine and a decrease in that toward L-methionine. In this study, we examined some properties of the C116H mutant by kinetic analysis and 3D structural analysis. We assumed that substitution of Cys116 for His broke the original hydrogen-bond network and that this induced a significant effect of Tyr114 as a general acid catalyst, possibly due to the narrow space in the active site. The C116H mutant acquired a novel β-elimination activity and lead a drastic conformation change in the histidine residue at position 116 by binding the substrate, suggesting that this His residue affects the reaction specificity of C116H. Furthermore, we suggest that Lys240* is important for substrate recognition and structural stability and that Asp241* is also involved in substrate specificity in the elimination reaction. Based on this, we suggest that the hydrogen-bond network among Cys116, Lys240*, and Asp241* contributes to substrate specificity that is, to L-methionine recognition at the active site in MGL&#95;Pp.

The objective of this study was to clarify the clinical significance and usefulness of measuring percent body fat (PBF) when compared with body mass index (BMI) in the Japanese population. A total of 2,483 Japanese individuals (1,380 men and 1,103 women) who underwent a medical checkup from 1999-2002 were employed. PBF was determined using bioelectrical impedance analysis (BIA). Relationships of age, BMI and PBF with several metabolic parameters, including blood pressure, lipids and plasma glucose levels were assessed in both genders separately. In men, PBF was a stronger determinant of total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C) and triglycerides (TG) compared with age and BMI, whereas in women, age was the strongest determinant of TC and LDL-C. In both genders, BMI was the strongest determinant of serum HDL-C among age, PBF and BMI. Based on these data, we suggest that measuring PBF by BIA is superior to BMI for predicting TC, LDL-C and TG in Japanese men.

Background: In Prader-Willi syndrome (PrWS), marked obesity is the most serious and common complication, contributing significantly to morbidity and mortality. Because of the associated psychosocial difficulties, bariatric surgery appears to be the only effective treatment., Case Report: A 30-year-old man with PrWS weighing 108 kg (BMI 50 kg/m2), underwent Roux-en-Y gastric bypass (RYGBP). 3 months before the RYGBP, he weighed 146 kg (BMI 68.5), partly because of heart failure. 18 months after RYGBP, he weighed 92.4 kg (BMI 43.3), with no postoperative complications. Moreover, he showed considerable increase in serum HDL-cholesterol levels with reciprocal reduction in LDL-cholesterol after the surgery., Conclusion: RYGBP resulted in satisfactory weight loss and improvement in serum lipid profile in a Japanese morbidly obese patient with PrWS.

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 HbA1c 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/m2] with fasting plasma glucose (PG) and HbA1c 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.

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-C > or = 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-C < 40 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%) (p < 0.001). Group H had a higher incidence of the G(-75)-->A transition (0.275) than Groups N (0.117, p < 0.05) and L (0.056, p < 0.01), 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) (p < 0.05). 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.

The essential aim of this study was to compare two different methods, Southern hybridization and fluorescence polarization (FP) assay. They both detect specific hybridization and were examined using common asymmetric PCR products and probes. FP assay clearly showed the hybridization of probe DNAs with the asymmetric PCR products of their target genes. Southern blot patterns presented excellent consistency with the results of FP assay. In both methods, two types of Shiga toxin (vero toxin) genes held in enterohaemorrhagic Escherichia coli (EHEC) were used as target genes. For detection of the two genes, stx1 and stx2, two respective DNA probes were synthesized. Both in FP assay and in Southern hybridization, the probe for stx1 hybridized only with the product of stx1 and vice versa. The results of the DNA detection using different methods were completely in agreement. Moreover, FP assay makes it possible to detect the hybridization rapidly. In our high NaCl concentration condition, hybridization between the probes and the asymmetric PCR products could be monitored within about 15min.

A 56-year-old woman with Werner's syndrome was admitted to our hospital because of intractable foot ulcer and malnutrition. She presented dementia consisting of childish behaviour, loss of intelligence, and severe amnesia. Brain CT revealed diffuse periventricular low density areas, and brain MRI also disclosed periventricular high intensity areas under T2-intensified conditions. These findings gave a diagnosis of progressive subcortical vascular encephalopathy of the Binswanger type, which seemed to be the cause of her dementia. She finally died of heart failure due to acute myocardial infarction. Mild to moderate demyelinization was found in the subcortical area of the autopsied cerebrum, confirming the clinical diagnosis. Generalized atherosclerosis characteristic of Werner's syndrome may have predisposed this patient to Binswanger's encephalopathy.

Objectives: The purpose of this study was to investigate the possibility of impaired lipolysis of triglyceride-rich lipoproteins in patients with abdominal visceral fat accumulation by assessing two major lipolytic enzymes in the plasma, lipoprotein lipase (LPL) and hepatic lipase (HL)., Design and Patients: A total of 31 patients [20 men, 11 women, age 50 +/- 7 years old, body mass index (BMI) 26 +/- 2 kg/m2 (mean +/- sd)] were analyzed. Visceral fat and subcutaneous fat areas were evaluated using a computerized tomographic (CT) method at the level of the umbilicus. Total lipolytic activity in the postheparin plasma (PHP) was measured using Triton X-100-emulsified triolein and LPL activity was calculated as the activity in whole plasma inhibited by the 5D2 monoclonal antibody for LPL. LPL enzyme mass was determined by a sandwich enzyme immunoassay., Results: The visceral fat area was found to be negatively correlated with LPL mass (V vs LPL mass, r = -0.37, P = 0.04) in PHP and had a tendency toward negative correlation with the LPL activity in the PHP (V vs LPL activity, r = -0.29, P = 0.12). Subcutaneous fat area, on the other hand, did not show any correlation with LPL activity (r = 0.13, P = 0.49) or mass (r = 0.22, P = 0.25) in the PHP. The visceral fat area was found to be positively correlated with fasting serum insulin levels (r = 0.67, P < 0.01). Body mass index (BMI) was not correlated with LPL mass or activity in the PHP. Multi-regressional analysis showed that abdominal visceral fat could be correlated with LPL mass in the PHP, independently of fasting serum insulin. The HL activity from PHP of the patients did not show significant correlation with visceral fat area, subcutaneous fat area or body mass index., Conclusions: Fat distribution affects LPL mass and activity, either directly or via another metabolic abnormality such as insulin resistance, leading to impaired hydrolysis of triglycerides in chylomicrons and very low density lipoproteins (VLDL) in these subjects.

Werner syndrome is a rare premature aging syndrome accompanied by severe atherosclerosis. The etiology of atherosclerosis is suspected to be due to its complications, namely diabetes mellitus, hyperinsulinemia and hyperlipidemia. But from an autopsy case we found that some other risk factors may be involved in the mechanism of atherosclerosis in this syndrome. Previously we revealed that the plasminogen activator inhibitor-1 (PAI-1) gene was being overexpressed in skin fibroblasts from a patient with this syndrome. PAI-1 is a potent inhibitor of tissue plasminogen activator and a possible risk factor of atherosclerosis. This led us to assess the plasma concentration of PAI-1. Our working hypothesis was that the PAI-1 gene was upregulated or not fully suppressed in cells responsible for the production of PAI-1 in plasma as well as in fibroblasts. The results show a high concentration of plasma PAI-1. One of the well-known physiological substances that induce the PAI-1 gene is tumor necrosis factor-alpha, which also induces other possible risk factors of atherosclerosis, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1. We found the serum concentrations of ICAM-1 to be elevated in patients with this syndrome. We conclude that high concentrations of PAI-1 and ICAM-1 in blood may be one of the potent causes of severe atherosclerosis in Werner syndrome.

Werner syndrome (WS) is an autosomal recessive disorder characterized by the premature occurrence of many age-related features. Previously, the WS gene (WRN) was mapped between D8S131 and D8S87, in an 8.3-cM interval. In this study, regions of homozygosity in 36 WS patients from inbred families were searched for by genotyping for 35 dinucleotide repeat polymorphic markers to narrow down the WRN critical region. The region most consistently homozygous in these patients was between the D8S1219/D8S1220 cluster and D8S278, within a 4.4-cM interval. For 16 markers mapped in this interval, 24 WS patients (22 Japanese patients and 2 Caucasian patients) in whom consanguinity failed to be proved were also genotyped, under the assumption that some of these patients might still be from consanguineous marriages. The data were analyzed by Fisher's exact test with a 2 x 2 contingency table for the 22 Japanese patients, excluding the 2 Caucasian patients. The frequencies of homozygosity in the 22 patients at 10 of 16 markers tested were significantly higher than those detected in the general population. Analysis of homozygosity patterns indicated that the region most consistently homozygous was between D8S1445 and D8S278. Thus the WRN locus is most likely between the two markers D8S1445 and D8S278, in a 1.6-cM interval.

Werner syndrome is a rare genetic disease of premature aging which manifests itself in the form of a variety of aging-like phenomena and diseases. It is an appropriate target for aging research because it is clear that the complications must be caused by one original gene defect. Another reason why this disease is of particular interest is observed at the cellular level. The abbreviated lifespan of cultured fibroblasts from patients with this disorder parallels the clinical features of this accelerated aging disease. Recent studies have met with some success in identifying certain genes involved in Werner syndrome and the roles they might play in normal cellular senescence. Such advances might result in a therapeutic breakthrough for this essentially incurable genetic disease. In addition, such a treatment might find some application in the control of the normal aging process.

It is apparent that personality is related to the pathogenesis of obesity, and that understanding the personality of the patient may be a key to successful treatment of the disease. Using the Rorschach test and interviews by a psychiatrist, the types of personality were classified into four groups according to the healthiness of personalities. The judgment of healthiness was based mainly on the scores obtained from the Rorschach test. This classification revealed that the occurrence of mental and physical symptoms during therapy with a very low calorie diet (VLCD) and subsequent rebound of bodyweight were more frequently observed in patients with relatively less healthy personalities. We used this classification to adapt our program to treat obese patients. In this program, severe diet restrictions were applied to patients with relatively healthy personalities. These restrictions were applied with modifications to patients with less healthy personality, because severe restrictions would be possibly very stressful for them and would bring about an undesirable reaction. For strengthening the patients' motivation for therapy, the significance of body weight reduction was explained in different ways to patients with different types of personality. The target of bodyweight reduction, reward for patients with successful weight reduction, and the duration of therapy were set up differently for patients with different personalities types. The results showed that bodyweight rebound one or two years after treatment was reduced with the personality-oriented therapy program compared to that observed with the previous conventional therapies. Also, the incidence of psychological problems was remarkably decreased.

An immobilized enzyme reactor, made up acylcarnitine hydrolase, carnitine dehydrogenase and diaphorase in sequence, was developed for the sensitive and selective determination of urinary free and individual acylcarnitines by a reversed-phase high-performance liquid chromatography. A 100-microliter urine sample was directly injected onto the TSKgel ODS 80Ts column and eluted by a step-gradient procedure. The eluent was mixed with the substrate solution of beta-NAD+ (1.0 mmol/l), resazurin (25 mumol/l) and Tris acetate (0.2 mol/l, pH 9.0). The mixture was passed through the immobilized enzyme reactor at 40 degrees C. Acylcarnitines were hydrolyzed and the converted to rezorufin which was measured by monitoring the fluorescence intensity at lambda EX = 560 nm and lambda EM = 580 nm. Free, acetyl-, glutaryl-, propionyl-, butyryl-, isobutyryl-, valeryl- and isovalerylcarnitine were determined within 55 min with detection limits (< 1 mumol/l) and within-run and day-to-day imprecision (C.V. < 6%). Free, acetyl- and isobutyrylcarnitine were found in normal urine. On the other hand, propionylcarnitine was detected in the urine of children with propionic aciduria and methylmalonic aciduria and multiple acylcarnitines were found in the urine of children with glutaric aciduria (type II).

Objective: To assess characteristics of long-living familial hypercholesterolemics (FHs) in comparison with younger patients., Design: Cross-sectional study., Setting: Lipid clinics of a university hospital and 14 related medical institutions., Patients: A total of 335 heterozygous FHs including 17 patients over 70 years old. The average ages of the aged (> or = 70 years old) and the younger groups were 73.5 +/- 3.7 and 46.5 +/- 15.0 years, respectively., Measurements: Medical history, serum lipids and apolipoproteins, and radiographic measurement of Achilles tendon xanthomas., Main Results: Age distribution of FHs suggests shorter life of FHs compared with the general population. The age distribution of FH females was shifted to older age compared with that of FH males (P < 0.01). No significant differences were found between the levels of serum lipids and apolipoproteins in the aged and the younger groups. The thickness of the Achilles tendon was positively correlated with the product of excess total serum cholesterol and age in the patients (P < 0.01). Progression of Achilles tendon thickening was less in females than in males. A few cases of longevity could not be explained by any of the anti-atherogenic factors including female gender, a relatively low concentration of serum total cholesterol, a high concentration of HLD-cholesterol, a non-smoking habit, and a familial predisposition for longevity., Conclusions: The female gender was found to be one of the most important factors for long survival of FHs. The different progression of Achilles tendon thickening in females and males may be related to the slower development of atherosclerosis and higher survival rate of the female patients.

The patient was a 74-year-old woman who had been obese since age 18. Her obesity was refractory to dietary manipulation. She had been suffering from increasing dyspnea for several months and eventually could not even move. She was admitted to a hospital and diagnosed as having heart failure. Although her cardiac function recovered with medical treatment, her symptoms did not improve. The patient was then sent to our hospital. On admission, her height and weight were 149 cm and 81.9 kg, respectively, yielding a body mass index (BMI) of 36.6 kg/m2. Arterial blood gas analysis in room air revealed hypoxemia and an apnea index of 27 per hour. She was given a daily 500-1000 kcal diet. After four months of treatment, her weight decreased to 65 kg with a BMI of 29.3 kg/m2. Weight reduction together with the usage of progesterone-derivatives resulted in marked improvement of sleep apnea. The apnea index decreased to 3/h and arterial blood gas values normalized. This patient seemed to have suffered from both obesity hypoventilation syndrome and sleep apnea syndrome. Improvement of respiratory function was achieved through relief of airway obstruction and weight reduction, with activation of the respiratory center due to progesterone treatment.

Werner syndrome (WS) is a recessive genetic condition associated with markedly reduced replicative lifespans of cells in culture, high chromosomal instability in vivo and in vitro, and premature appearance of many characteristics of normal aging, including an increased incidence of cancer. We have monitored plasmid homologous recombination frequencies in diploid fibroblasts from 6 Werner or Werner-like syndrome patients, following transfection with a plasmid substrate containing 2 overlapping fragments of the TN5 Neor gene. Plasmid DNA recovered from these cells was then assayed for homologous recombination by (a) transformation of recA- bacteria to Ampr (indicating total viable plasmid) or Neor (indicating viable recombinant plasmid), and (b) by limited-cycle polymerase chain reaction (PCR) to co-amplify a recombinant fragment containing the overlap region, and a control region of the same plasmid, without bacterial transformation. Bacterial assay data indicated that recombination rates in 3 of the 6 WS strains were significantly elevated above normal controls; 4 of 6 appeared elevated by PCR assay. The highest-recombination WS strain showed evidence of reduced degradation of transfected plasmid DNA. For this small sample of WS strains, clinical severity of WS was not well correlated with recombination rate as determined by either assay (Pearson r = 0.78, not significant, for PCR assay); elevated recombination may, however, define a subset of WS at greatest risk for cancer and/or atherosclerosis. PCR assay of a hyperoxia-resistant HeLa cell line, displaying substantially increased chromosome breakage, indicated increased recombination between direct-repeat fragments. Nevertheless, elevated recombination in WS strains is unlikely to be secondary to impaired replicative capacity characteristic of WS cells, or to defective repair of chromosome damage which is increased in WS, since recombination in non-WS strains was unaffected by passage level or repeated UV irradiation.

Thirty-four hyperlipoproteinemic, hypertensive patients received 5 mg of pindolol twice daily for 12 weeks. During pindolol administration, there were significant decreases in serum triglyceride levels and increases in high-density lipoprotein cholesterol (HDL-C) levels, while total cholesterol levels did not change. Serum levels of very-low-density lipoprotein (VLDL) triglyceride and VLDL cholesterol decreased over time as HDL-C increased. There was a significant increase in low-density lipoprotein cholesterol at week 12. Apolipoprotein (apo) A-I, A-II, and B levels did not change during pindolol administration, but apo C-II, C-III, and E levels decreased significantly. Lipoprotein lipase activity in heparin-treated plasma was significantly higher after pindolol administration. The results suggest that the reduction in triglyceride levels and increase in HDL-C after pindolol are partly a response to an increase in the hydrolysis of VLDL resulting from an increase in lipoprotein lipase activity.

The total serum cholesterol level in rats fed on a high cholesterol diet (HCD) for 16 weeks was markedly higher than that in rats fed on a normal diet (ND), but pantethine reduced the increased level in rats fed on HCD (P less than 0.05). Acid cholesterol esterase activity (acid CEase) of arterial wall homogenates from rats fed on HCD was significantly lower than that of rats fed on ND (P less than 0.005). Acid CEase activity in the arterial wall of rats fed on HCD for 8 weeks and then ND for 8 weeks was less than that of rats fed on ND for 16 weeks. Acid CEase activity in the arterial wall was increased in rats fed on pantethine-containing diet. The ratio of cholesterol ester synthesizing activity to neutral cholesterol esterase (neutral CEase) activity was higher in rats fed on NCD than in those fed on ND. The ratio was lower in rats on the pantethine-containing diet than in those on NCD. The relationship between hypercholesterolemia and lipid metabolism in the arterial wall and effects of pantethine are discussed on the basis of these results.

Extraction of the cytoplasm of rat liver with 5% PCA and subsequent TCA (20%) treatment resulted in the recovery of only a few proteins, the predominant one having an apparent molecular weight of 12K. This 12K protein increased sharply (9-fold) between 2 weeks and 10-20 weeks and then decreased until at least 2 years after birth. 12K protein was separated into two components, 12K-1 (larger) and 12K-2 (smaller), by gel chromatography which had similar amino acid compositions to those of profilin (from Acanthamoeba and hog thyroid). Like profilin, 12K-1 protein inhibited the rate of actin polymerization, while 12K-2 protein did not. These findings suggest that liver profilin-like proteins increase sharply during development.

The effects of dietary tocopherol deficiency on arterial wall enzymes involved in lipid synthesis and hydrolysis were studied in rats receiving normal diets and diets supplemented with 1% cholesterol. Arterial wall lipase and cholesterol esterase were associated with both the lysosome and microsome fractions, whereas acyl CoA synthetase, triglyceride synthesizing activity, cholesteryl ester synthesizing activity and cytidine diphosphatecholine-1,2-diacyl glycerol choline phosphotransferase (CPT) were found mainly in the microsomal fraction. When tocopherol was depleted from either the normal or high cholesterol diets, the following changes occurred in the arterial wall: (1) increase in thiobarbituric acid reactive substances; (2) decrease in lysosomal acid lipase and acid cholesteryl esterase; (3) decrease in the microsomal enzymes, acyl CoA synthetase, triglyceride synthesizing activity, cholesteryl ester synthesizing activity, neutral lipase and neutral cholesteryl esterase; and (4) increase in microsomal CPT. The results of these studies suggest that dietary tocopherol plays an important role in both lipid synthesis and degradation in the arterial wall, and the results may account for the accumulation of lipids and lipoperoxides in atherosclerotic lesions.

Atherosclerotic lesions formed in the aorta of rats given diet containing propylthiouracil (PTU), vitamin D2 and high cholesterol diet (atherogenic) for 8 weeks. The effect of clinofibrate, which lowers the plasma lipid level, on lipid metabolism in the arterial wall of the atherosclerotic rats was studied. Clinofibrate significantly decreased the high plasma cholesterol level of atherosclerotic rats, which was 823 +/- 256 (mean +/- SD) mg/dl, or about ten times that of control rats (85 +/- 11 mg/dl). On treatment with clinofibrate, the cholesterol level was reduced most in the very low density lipoprotein (VLDL) fraction (d less than 1.006). Heparin-releasable lipoprotein lipase activity in epididymal adipose tissue, lipoprotein lipase activity in post heparin plasma, and VLDL-triolein hydrolizing activity in adipose tissue stromal vessels were higher in clinofibrate-treated rats than in atherosclerotic rats. Of the enzymes in the arterial wall concerned with cholesterol ester metabolism, acid cholesterol esterase activity was decreased in atherosclerotic rats, and clinofibrate treatment increased this activity. The ratio of acyl-CoA cholesterol acyltransferase activity (ACAT) to neutral cholesterol esterase activity was higher in atherosclerotic rats than in control rats and was lower in clinofibrate-treated rats than in atherosclerotic rats. From these results, it is concluded that clinofibrate modifies enzyme activities in such a way as to cause a reduction of cholesterol accumulation in the arterial wall and lowers the plasma VLDL and LDL cholesterol levels.

Captopril (37.5 mg daily) was administered to 64 hypertensive patients for 16 weeks. During treatment, systolic and diastolic blood pressures decreased significantly (from means of 164/98 mmHg before treatment to 150/90 mmHg at four weeks and 142/86 mmHg at eight weeks; P less than 0.001), but serum levels of total cholesterol, triglycerides, lipoprotein cholesterol, lipoprotein triglyceride, and apolipoproteins showed no significant changes. Scores on the atherogenic index did not change. Patients with high initial total cholesterol levels and low high-density lipoprotein cholesterol levels tended to improve their lipid levels. It is concluded that captopril does not adversely affect serum lipoprotein metabolism.

Lipid metabolism in the arterial wall of spontaneously hypertensive rats (SHR) fed on tocopherol-deficient diet, high-cholesterol diet or both was studied. Serum tocopherol was greatly decreased in tocopherol-deficient SHR. Lipoperoxide, determined as thiobarbituric acid-reactive substances, was higher in tocopherol-deficient SHR than in normal SHR. Tocopherol-deficient SHR showed a decrease in acid cholesterol esterase activity, but no change in neutral cholesterol esterase, acid and neutral lipase, acyl CoA synthetase, cytidine-diphosphate choline-1-2-diacyl glycerol choline phosphotransferase (CPT) or triglyceride synthesizing activity.

Atherosclerotic lesions were formed in the aorta of rats given a high cholesterol diet containing propylthiouracil (PTU) and vitamin D2 (atherogenic diet) for 8 weeks. The effects of niceritrol (pentaerythritol tetranicotinate), which lower the plasma lipid level, on lipid metabolism in the arterial wall of the atherosclerotic rats were studied. Niceritrol significantly decreased the plasma cholesterol level of atherosclerotic rats, which was 823 mg/100 ml, or about ten times that of control rats. On treatment with niceritrol, the cholesterol level was reduced most in the very low density lipoprotein (VLDL) fraction (d less than 1.006). Heparin-releasable lipoprotein lipase activity in epididymal adipose tissue, lipoprotein lipase activity in post-heparin plasma, and VLDL-triolein hydrolyzing activity in adipose tissue stromal vessels were all higher in niceritrol-treated atherosclerotic rats. Of the enzymes in the arterial wall concerned with cholesterol ester metabolism, acid cholesterol esterase activity was decreased in atherosclerotic rats, while niceritrol treatment increased this activity. The ratio of acyl-CoA cholesterol acyltransferase activity (ACAT) to neutral cholesterol esterase activity was higher in atherosclerotic rats than in control rats, but was lower in niceritrol-treated rats than in atherosclerotic rats. From these results, it is concluded that niceritrol modifies enzyme activities in such a way as to reduce the cholesterol ester content of the arterial wall and lower plasma VLDL and LDL cholesterol levels.

A ninth Japanese patient afflicted with lecithin-cholesterol acyltransferase (LCAT) deficiency is described with emphasis on renal pathology. The most striking feature is massive deposition of lipid material in the glomeruli, particularly in the glomerular basement membrane (GBM) and in the mesangial region. The glomerular changes appear to be similar to that seen in some cases with cirrhosis of the liver. Lipid material contains a large amount of apolipoprotein-B detected by immunohistology. In two renal biopsies, taken three years apart, renal pathology is essentially the same and glomerular pathology is most characteristic. It is suggested that lipid deposition in glomeruli in this patient is rather slow. Family study of the present case reveals consanguinous marriages in the previous two generations suggesting the exaggerated gene expression of LCAT deficiency in this family.

A new lecithin:cholesterol acyltransferase (LCAT)-deficient family was found in Japan. In the proband, both LCAT activity and LCAT mass were deficient. The patient's parents, child, and sister, diagnosed as heterozygotes, had half-normal LCAT activity and LCAT mass. In the patient, an increase of intermediate-density lipoprotein (IDL, 1.006 less than d less than 1.019) fraction was observed. In postheparin plasma, both lipoprotein lipase and hepatic triglyceride lipase activities were low. Hydrolysis of [14C] triolein by human hepatic triglyceride lipase in patient IDL was decreased compared to that in IDL from normal postprandial serum. Preincubation of these IDL with normal plasma in the absence of 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB) increased the rate of hydrolysis, in the presence of DTNB, this increment was not observed. These results suggest that one cause of IDL increase in the LCAT-deficient patient might be the difficulty of hydrolysis of these lipoprotein particles by hepatic triglyceride lipase.

The acute effects of propranolol and acebutolol on blood pressure, heart rate and hormonal changes during graded treadmill exercise were studied in patients with essential hypertension. Both of propranolol (2 mg i.v.) and acebutolol (10 mg i.v.) lowered the pre-exercise hemodynamic parameters and suppressed the elevation of systolic blood pressure, heart rate and pressure-rate product during exercise, but did not show any significant effect on diastolic blood pressure. Although these drugs increased plasma norepinephrine concentration (PNE) at rest and during moderate exercise, they failed to affect PNE at submaximal exercise. Plasma renin activity at rest and during exercise were more strongly suppressed by propranolol than acebutolol. Plasma aldosterone concentration was not affected by these drugs. Propranolol and acebutolol showed similar acute effects on blood pressure, heart rate and hormonal profiles at rest and during exercise within the doses used in this study. These results indicate that beta 1 adrenoceptor selectivity and intrinsic sympathomimetic activity may not play an important role in the acute antihypertensive effect at rest and during exercise and that both beta blockers have beneficial antihypertensive effects during exercise on patients with essential hypertension.

Arteriosclerotic lesions were formed in rat aorta by the administration of vitamin D2, a high-fat diet and a thyroid suppressing agent. This treatment increased the serum total cholesterol level to 12 times the control level. In the arteriosclerotic lesions that were induced the activities of lysosomal enzymes, such as acid phosphatase and acid lipase, were higher than in controls, that of acid cholesterol esterase was decreased, those of microsomal lipid-synthesizing enzymes--such as acyl-CoA synthetase and cholesterol ester synthesizing activity--were increased and that of neutral cholesterol esterase was decreased. These data suggest that lipid metabolism in arteriosclerotic lesions was changed, resulting in the accumulation of cholesterol esters in the aorta. Administration of high-fat diet and thyroid suppressing agent also increased the serum cholesterol levels to 12-fold the control level, but did not induce arteriosclerotic lesions. After this treatment the activities of hydrolyzing enzymes, such as acid and neutral cholesterol esterase and lipase, in the aorta increased, but the activities of lipid synthesizing enzymes also increased. These data suggest that lipid metabolism in the aorta in this condition changed to compensate for the large influx of serum lipids and to prevent arteriosclerosis. The roles of the serum lipid level, cell injury and lipid metabolism in the aorta in forming arteriosclerotic lesions are discussed on the basis of these results.

Premature development of atherosclerosis is a fatal complication together with cancer in patients with Werner' syndrome, a known syndrome of premature aging. Proliferation of arterial smooth muscle cells (SMC) is a key event in the formation of atherosclerosis. This paper studied the serum growth promoting activity of Werner's syndrome in cultured rabbit aortic SMC. Serum of cases of Werner's syndrome showed significantly higher growth-promoting activities than those of age-matched controls. The levels of serum growth hormone, plasma somatomedin C, and urine epidermal growth factor were not increased in Werner's syndrome. The level of serum insulin was generally increased in Werner's syndrome. However, there was no correlation between serum insulin level and growth promoting activity, and the effective dose of insulin for the promotion of SMC growth was ten thousand times higher than that contained in the serum. The above results suggest that elevated serum growth-promoting activity in Werner's syndrome is in part responsible for the premature atherosclerosis and that this elevated activity is derived from either platelet derived growth factor or an unknown growth factor(s) contained in the serum.