Female reproductive factors and risk of all-cause and cause-specific mortality among women: The Japan Public Health Center–based Prospective Study (JPHC study)

Purpose

We investigated the association between reproductive history and mortality from all and major causes among Japanese women.

Development of gelatin flakes, a new type of anti-adhesive material: a preliminary study of in vivo rat adhesion models

To overcome the problems associated with sheet- or film-type anti-adhesive materials, we developed a new type of anti-adhesive material, gelatin flakes. We made two types of gelatin flakes with or without thermal cross-linking, and preliminarily examined their basic properties and the anti-adhesive efficacy using a rodent adhesion model. Both types of the gelatin flakes rapidly turned into gel and tightly attached the injured surfaces, absorbing the moisture and blood, when applied onto the abraded sites of rats. In addition, these flakes could be sprayed into the desired area by compressed air through a device with a long, thin tube, which could be used in laparoscopic surgery. The anti-adhesive effects of both types of gelatin flakes were similar, and both types were significantly superior compared to the non-treated group. Although further investigations are necessary, the gelatin flakes have unique and useful properties and satisfactory anti-adhesive effects, which indicate that they may be applicable in laparoscopic surgery.     

Significance of combined cyclosporine−prednisolone therapy and cyclosporine blood concentration monitoring for idiopathic membranous nephropathy with steroid-resistant nephrotic syndrome: a randomized controlled multicenter trial

Background

Combined treatment with cyclosporine microemulsion preconcentrate (CyA MEPC) and steroids has been widely used for idiopathic membranous nephropathy (IMN) associated with steroid-resistant nephrotic syndrome (SRNS). Recent studies have shown that once-a-day and preprandial administration of CyA MEPC is more advantageous than the conventional twice-a-day administration in achieving the target blood CyA concentration at 2 h post dose (C2). We designed a randomized trial to compare these administrations.

Methods

IMN patients with SRNS (age 16–75 years) were divided prospectively and randomly into 2 groups. In group 1 (n = 23), 2–3 mg/kg body weight (BW) CyA MEPC was given orally once a day before breakfast. In group 2 (n = 25), 1.5 mg/kg BW CyA MEPC was given twice a day before meals. CyA + prednisolone was continued for 48 weeks.

Results

Group 1 showed a significantly higher cumulative complete remission (CR) rate (p = 0.0282), but not when incomplete remission 1 (ICR1; urine protein 0.3–1.0 g/day) was added (p = 0.314). Because a C2 of 600 ng/mL was determined as the best cut-off point, groups 1 and 2 were further divided into subgroups A (C2 ≥600 ng/mL) and B (C2 <600 ng/mL). Groups 1A and 2A revealed significantly higher cumulative remission (CR + ICR1) (p = 0.0069) and CR-alone (p = 0.0028) rates. On the other hand, 3 patients with high CyA levels (C2 >900 ng/mL) in Group 1A were withdrawn from the study because of complications.

Conclusion

CyA + prednisolone treatment is effective for IMN with associated SRNS at a C2 of ≥600 ng/mL. To achieve remission, preprandial once-a-day administration of CyA at 2–3 mg/kg BW may be the most appropriate option. However, we should adjust the dosage of CyA by therapeutic drug monitoring to avoid complications.     

Chylomicronemia caused by lipoprotein lipase gene mutation related to a hyper-response of insulin secretion to glucose

A 39-year-old man with lipoprotein lipase (LPL) deficiency (height 177.7 cm, body weight 67 kg, and body mass index 21.2 kg/m2) showed severe hypertriglyceridemia (2,032 mg/dl). LPL activity and concentration were markedly low in postheparin plasma. LPL gene analysis revealed a homozygous mutation, Asp204 --> Glu in exon 5. Fasting plasma glucose (81 mg/dl) and insulin (2.7 microU/ml) levels were normal. Plasma glucose pattern during oral glucose (75 g) tolerance test was normal, however 30 minutes after glucose-loading the insulin secretion unexpectedly increased to 89.4 microU/ml. These data suggested that chylomicronemia might be related to a hyper-response of insulin secretion to glucose without obesity.     

C-reactive protein and peripheral artery disease among Japanese elderly: the Tsurugaya Project.

We investigated the cross-sectional relationship between ankle brachial index and cardiovascular disease risk factors, including C-reactive protein (CRP), among Japanese elderly, a topic which has had little prior epidemiologic study. Our study population comprised 946 subjects aged at least 70 years in whom both CRP and ankle brachial index were measured. The participants were classified into a low (ankle brachial index<0.9) and normal ankle brachial index group. We found that current smoking, high-density lipoprotein cholesterol <40 mg/dl, a low body mass index (continuous variable), hypertension, diabetes and statin use were all significantly related to a lower ankle brachial index. Higher log-transformed CRP level was significantly related to a lower ankle brachial index after adjustment for the cardiovascular risk factors mentioned above (p <0.01). The odds ratios for low ankle brachial index compared to 0-1 risk factors were 5.79 (95% confidence interval [CI]: 2.99-11.20) for 2 risk factors and 17.45 (95% CI: 6.78-49.91) for 3 or more risk factors; independently of other risk factors, the odds ratio for CRP>1.0 mg/l was 2.10 (95% CI: 1.13-3.88) compared to lower CRP values. Thus, a high level of CRP is related to a low ankle brachial index among Japanese elderly as well as Western subjects. This is the first study to report the relationship between CRP and low ankle brachial index among Japanese elderly.     

Patterns of and risk factors for recurrence after liver resection for well-differentiated hepatocellular carcinoma: a special reference to multicentric carcinogenesis after operation

BACKGROUND/AIMS: We studied the patterns of, and risk factors for, recurrence after resection of well-differentiated hepatocellular carcinoma to make a strategy for such carcinoma. METHODOLOGY: The subjects were 36 patients who underwent liver resection for well-differentiated hepatocellular carcinoma. Multicentric carcinogenesis after the operation (multicentric recurrence) was diagnosed when a recurrent tumor included a component of well-differentiated hepatocellular carcinoma. Tumor-free survival rates of patients with various risk factors were calculated and differences between groups were evaluated. For multivariate analysis, Cox's proportional hazard model was used. RESULTS: All recurrent tumors after operation were of multicentric origin. Univariate analysis showed a history of blood transfusion, high alpha-fetoprotein concentration (> 20 ng/ml), and low platelet count (< 10(5)/mm3) to be significant factors. By multivariate analysis, a history of blood transfusion and a low platelet count were independent risk factors. Nonanatomic resection was not a risk factor. CONCLUSIONS: In patients with well-differentiated hepatocellular carcinoma, especially with risk factor(s) for multicentric recurrence, not only anatomic but also nonanatomic resection (partial resection) are indicated for a primary tumor, because almost all recurrent tumors are of multicentric origin. After resection of well-differentiated hepatocellular carcinoma, careful monitoring for multicentric recurrence is important in patients with risk factors.     

Ovariectomy Aggravated Sodium Induced Hypertension Associated With Altered Platelet Intracellular Ca in Dahl Rats

Our purpose was to determine the effect of ovariectomy on intracellular Ca²⁺ mobilization and platelet aggregation in sodium induced hypertension. At the age of 12 weeks ovariectomy or sham operation was performed in female Dahl-Iwai salt sensitive rats on a 0.3% NaCl diet. Four weeks later we assessed the effects of ovariectomy and an 8% NaCl diet on agonist induced intracellular Ca²⁺ mobilization in fura-2 loaded platelets and platelet aggregation. Ovariectomy enhanced the increase of systolic blood pressure and heart to body weight ratio on an 8% NaCl diet. However, thrombin evoked intracellular Ca²⁺ was not correlated with systolic blood pressure (r = −0.338, P = .17), and was lowered by sodium loading and ovariectomy (360 ± 23 to 285 ± 9, 296 ± 10 nmol/L, P < .05). Furthermore, the ionomycin induced intracellular calcium fraction in the absence of external Ca²⁺ that reflected internal Ca²⁺ discharge capacity was reduced in ovariectomized rats compared with sham operated rats on an 8% NaCl diet (648 ± 15 v 768 ± 35 nmol/L, P < .05). The internal Ca²⁺ discharge capacity was inversely correlated with systolic blood pressure (r = −0.506, P = .03). In addition to the decreased internal Ca²⁺ discharge capacity, intracellular Ca²⁺-independent platelet aggregation by phorbol 12-myristate 13-acetate, a protein kinase C activator, was significantly enhanced in hypertensive rats. We concluded that ovariectomy enhanced sodium induced hypertension associated with the decreased internal Ca²⁺ discharge capacity and increased platelet aggregation in Dahl-Iwai salt-sensitive rats.     

Degradation of p57Kip2 mediated by SCFSkp2-dependent ubiquitylation

The abundance of the cyclin-dependent kinase (CDK) inhibitor p57Kip2, an important regulator of cell cycle progression, is thought to be controlled by the ubiquitin-proteasome pathway. The Skp1/Cul1/F-box (SCF)-type E3 ubiquitin ligase complex SCFSkp2 has now been shown to be responsible for regulating the cellular level of p57Kip2 by targeting it for ubiquitylation and proteolysis. The elimination of p57Kip2 was impaired in Skp2-/- cells, resulting in abnormal accumulation of the protein. Coimmunoprecipitation analysis also revealed that Skp2 interacts with p57Kip2 in vivo. Overexpression of WT Skp2 promoted degradation of p57Kip2, whereas expression of a dominant negative mutant of Skp2 prolonged the half-life of p57Kip2. Mutation of the threonine residue (Thr-310) of human p57Kip2 that is conserved between the COOH-terminal QT domains of p57Kip2 and p27Kip1 prevented the effect of Skp2 on the stability of p57Kip2, suggesting that phosphorylation at this site is required for SCFSkp2-mediated ubiquitylation. Finally, the purified recombinant SCFSkp2 complex mediated p57Kip2 ubiquitylation in vitro in a manner dependent on the presence of the cyclin E-CDK2 complex. These observations thus demonstrate that the SCFSkp2 complex plays an important role in cell-cycle progression by determining the abundance of p57Kip2 and that of the related CDK inhibitor p27Kip1.     

Disseminated toxoplasmosis after hematopoietic stem cell transplantation showing unusual magnetic resonance images

We herein report a patient who had disseminated toxoplasmosis after hematopoietic stem cell transplantation showing atypical clinical presentation and neuroimaging. Parkinsonism symptoms such as muscle rigidity, bradykinesia, tremor, and postural instability were initial manifestations. Magnetic resonance imaging showed diffuse symmetrical lesions of bilateral basal ganglia lacking ringed enhancement. Post‐mortem analysis revealed multiple tachyzoites of Toxoplasma gondii in the basal ganglia, mid brain, cerebellum, and cardiac muscle.     

Alterations to Titanium Surface Depending on the Fluorides and Abrasives in Toothpaste

Fluoride and abrasives in toothpastes may cause corrosion and deterioration of the titanium used for implants and other prostheses. The purpose of this study was to investigate how the presence or absence and types of fluoride and abrasives affected the titanium surface texture. Brushing with toothpastes was performed on pure-titanium discs using an abrasive testing machine. Unprocessed titanium discs without brushing were used as control samples. Surface roughness, color, and gloss of titanium were measured and the differences compared with the control were analyzed. Additionally, titanium surfaces and abrasives in toothpastes were observed using a scanning electron microscope to compare the surface texture of each sample. Some toothpastes (abrasive+) significantly increased the difference in surface roughness, color, and gloss, compared with ultrapure water. Toothpaste (fluoride+/abrasive+) that had many polygonal abrasive particles led to the largest color differences and exhibited notable scratches and a larger number of contaminant- or corrosion-like black spots. In contrast, brushing with toothpaste without fluoride or abrasives (fluoride−/abrasive−) caused little change to the titanium surface. These results suggest that both fluoride and abrasives in toothpaste used for brushing may be factors that affect surface texture and corrosion resistance of titanium.