The production of coagulation factor VII by adipocytes is enhanced by tumor necrosis factor-α or isoproterenol.

BACKGROUND: A relationship has been reported between blood concentrations of coagulation factor VII (FVII) and obesity. In addition to its role in coagulation, FVII has been shown to inhibit insulin signals in adipocytes. However, the production of FVII by adipocytes remains unclear. OBJECTIVE: We herein investigated the production and secretion of FVII by adipocytes, especially in relation to obesity-related conditions including adipose inflammation and sympathetic nerve activation. METHODS: C57Bl/6J mice were fed a low- or high-fat diet and the expression of FVII messenger RNA (mRNA) was then examined in adipose tissue. 3T3-L1 cells were used as an adipocyte model for in vitro experiments in which these cells were treated with tumor necrosis factor-α (TNF-α) or isoproterenol. The expression and secretion of FVII were assessed by quantitative real-time PCR, Western blotting and enzyme-linked immunosorbent assays. RESULTS: The expression of FVII mRNA in the adipose tissue of mice fed with high-fat diet was significantly higher than that in mice fed with low-fat diet. Expression of the FVII gene and protein was induced during adipogenesis and maintained in mature adipocytes. The expression and secretion of FVII mRNA were increased in the culture medium of 3T3-L1 adipocytes treated with TNF-α, and these effects were blocked when these cells were exposed to inhibitors of mitogen-activated kinases or NF-κB activation. The ß-adrenoceptor agonist isoproterenol stimulated the secretion of FVII from mature adipocytes via the cyclic AMP/protein kinase A pathway. Blockade of secreted FVII with the anti-FVII antibody did not affect the phosphorylation of Akt in the isoproterenol-stimulated adipocytes. CONCLUSION: Obese adipose tissue produced FVII. The production and secretion of FVII by adipocytes was enhanced by TNF-α or isoproterenol via different mechanisms. These results indicate that FVII is an adipokine that plays an important role in the pathogenesis of obesity.

Energetics of active fluctuations in living cells.

The nonequilibrium activity taking place in a living cell can be monitored with a tracer embedded in the medium. While microrheology experiments based on optical manipulation of such probes have become increasingly standard, we put forward a number of experiments with alternative protocols that, we claim, will provide insight into the energetics of active fluctuations. These are based on either performing thermodynamiclike cycles in control-parameter space or determining response to external perturbations of the confining trap beyond simple translation. We illustrate our proposals on an active itinerant Brownian oscillator modeling the dynamics of a probe embedded in a living medium.

Initial evaluation of a novel multibending backward-oblique viewing duodenoscope in endoscopic retrograde cholangiopancreatography.

A novel multibending backward-oblique viewing duodenoscope was developed to overcome the difficult technical aspect of deep cannulation into the bile duct during endoscopic retrograde cholangiopancreatography (ERCP). The aim of the present study was to evaluate the initial experience of a novel multibending backward-oblique viewing duodenoscope (M-D scope) for ERCP. This was a retrospective review of 23 patients with native papilla who received biliary ERCP with the M-D scope between April and December 2010. The procedures were performed by two well-experienced endoscopists. In all patients, biliary cannulation and therapeutic procedure were successfully completed. In two patients with Billroth I gastrectomy, ERCP were initially attempted with a conventional single-bending duodenoscope, but biliary cannulations were unsuccessful. However, with the use of the M-D scope, biliary cannulation and therapeutic procedures were successfully completed. A novel multibending backward-oblique viewing duodenoscope is safe and feasible for therapeutic and diagnostic ERCP.

Dependence on the electric power of the immersion-angle dependence of the resonant-frequency shift of a quartz crystal microbalance in a liquid.

We have investigated the immersion-angle dependence of the series resonant-frequency shift, DeltaF, of the quartz crystal microbalance, QCM, in a Newtonian liquid from the point of view of the supplied electric power level. In the low electric power levels, the immersion-angle dependence and the transition phenomenon of the DeltaF are observed. However, when the higher electric power levels are supplied to the QCM, the region of the transition phenomenon of the DeltaF decreases rapidly with an increase in the electric power level and disappears above 1.5 dBm. That is, above 1.5 dBm, the DeltaF values have only the values of 90 degrees immersion angle in all immersion angles. We suggest that the electric power is very important factor for the DeltaF in a liquid.

Multicentre prospective study of perinatal depression in Japan: incidence and correlates of antenatal and postnatal depression.

A multicentre study on the epidemiology of perinatal depression was conducted among Japanese women expecting the first baby (N = 290). The incidence rate of the onset of the DSM-III-R Major Depressive Episode during pregnancy (antenatal depression) and within 3 months after delivery (postnatal depression) were 5.6% and 5.0%, respectively. Women with antenatal depression were characterised by young age and negative attitude towards the current pregnancy, whereas women with postnatal depression were characterised by poor accommodation, dissatisfaction with sex of the newborn baby and with the emotional undermining. Antenatal depression was a major risk factor for postnatal depression.

Capillary aging of the contacts between glass spheres and a quartz resonator surface.

The strength of the contacts between small glass spheres and the surface of a quartz crystal resonator has been probed based on the increase of resonance frequency induced upon sphere contact. The acoustic interaction between the sphere and the plate is modeled as a low-frequency coupled resonance; the dependence of the resonant parameters on overtone order lends support to this model. After exposing the sample to humid air and drying it again, the contact strength increases at least tenfold due to capillary forces--we observe a hysteretic form of the sand-castle effect. Repeated wet-dry cycles reveal logarithmic capillary aging with time. The experiments suggest that the drying of the liquid bridges leads to a contraction of small voids in the contact zone, subsequently increasing cohesion.

Prevalence of human papillomavirus in cervical swabs in the Okinawa Islands, Japan.

Although human papillomavirus (HPV) is the main risk factor for invasive cervical cancer, the mechanisms of developing carcinoma are not entirely understood. In particular, the biology and natural history of HPV infection are still unknown. Therefore, we have investigated the incidence of human papillomavirus infection by polymerase chain reaction (PCR) in cervical swabs obtained from women who had cervical cancer screening in three separate areas of the islands of Okinawa. The prevalence of HPV in women aged between 30 and 85 years in the three local areas, Yonashiro-town, Naha-city, and Hirara-city, was consistent (9 to 10%). HPV of various oncogenic types, including HPV16, 18, 31, 33, 35, 35, and 58, were identified in HPV-positive swabs and the prevalence of these types varied in the three areas.

Post-partum maternity 'blues' as a reflection of newborn nursing care in Japan.

OBJECTIVES: To investigate the prevalence of post-partum 'blues' in mothers whose babies are cared for in a newborn nursery, compared with mothers providing rooming-in care. METHODS: Japanese normal primiparous women were prospectively studied from 1998 to 1999. The newborns of these mothers were managed in the newborn nursery or by rooming-in care. To diagnose maternity 'blues' and 'depression', the Stein's Questionnaire and the Edinburgh Postnatal Depression Scale were used. RESULTS: Ninety-seven and 93 women were managed by newborn nursery care and by rooming-in care, respectively. Of these women, a total of 181 women were considered for analysis. 'Blues' was noted in 31 of 92 mothers (33.7%) receiving newborn nursery care and in 18 of 89 (20.2%) receiving rooming-in care with a significant difference (P<0.05), and in 49 of 181 (27.1%) as a whole. The daily Stein's scores changed significantly during the 10 days post-partum in each group (P<0.0001). Post-partum 'depression' was observed in three mothers (3.4%) in the newborn nursery care group and in four (4.8%) of the rooming-in care group, not a significant difference, and in seven (4.1%) as a whole. CONCLUSION: Maternity 'blues' is experienced by 25% or more of Japanese primiparous women delivering healthy babies via uncomplicated delivery. The system of newborn nursery infant care may be a potential causal factor for maternity 'blues', although it should be confirmed by a prospective randomized trial.

In vitro and in vivo activities of meropenem and comparable antimicrobial agents against Haemophilus influenzae, including beta-lactamase-negative ampicillin-resistant strains.

The in vitro activity of ampicillin, cefotaxime, meropenem, panipenem, imipenem and biapenem was assayed using ampicillin-susceptible, beta-lactamase-positive and beta-lactamase-negative ampicillin-resistant (BLNAR) Haemophilus influenzae isolated recently in Japan. Against ampicillin-susceptible isolates, cefotaxime was the most potent (MIC(90) 0.016 mg/mL). Both cefotaxime and meropenem (MIC(90) of both, 0.5 mg/L) were the most potent against beta-lactamase-positive isolates. Against BLNAR isolates, meropenem (MIC(90) 0.5 mg/L) was the most potent. In murine bronchopneumonia caused by ampicillin-susceptible and BLNAR H. influenzae, cefotaxime showed the best efficacy, followed by meropenem. Our results indicate that meropenem could be a useful intravenous agent for infections caused by H. influenzae, including BLNAR strains.

Upregulation of the pro-apoptotic BH3-only peptide harakiri in spinal neurons of amyotrophic lateral sclerosis patients.

DNA fragmentation and activation of caspase-1, implicating involvement of apoptosis, have been reported in the spinal cord of amyotrophic lateral sclerosis (ALS) patients and transgenic mouse models of ALS. Because BH3-only members of the Bcl-2 family have pro-apoptotic activity, we examined the expression of the BH3-only peptide harakiri (Hrk) in the spinal cord of ALS patients. In situ expression of Hrk mRNA and immunoreactivity against the Hrk peptide were verified in the spinal neurons. In the immunoblot analysis, upregulated Hrk protein migrated at 16 kDa. Heterodimerization of Hrk with Bcl-2 was detected by immunoprecipitation, which suggests the competition of Hrk and anti-apoptotic Bcl-2. These findings suggest that Hrk plays a role in apoptotic events in ALS pathogenesis.

Restoration of menstruation after chemotherapy-induced amenorrhoea in a patient with ovarian immature teratoma.

We described a rare case of a 20-year-old woman with an ovarian immature teratoma who resumed regular spontaneous menses after more than 5 years of chemotherapy-induced amenorrhoea. Efforts to reverse chemotherapy-induced ovarian failure can be continued even after persistent menstrual dysfunction of 5 or more years.

Pelvic floor disturbance after childbirth: vaginal delivery damages the upper levels of sphincter innervation.

PURPOSE: Vaginal delivery disturbs pelvic floor innervation, which has previously been studied as a single mechanism. The effects of childbirth on innervation at different levels of the anal sphincter system were studied after childbirth. METHODS: Both anal manometry and motor latencies were measured in 67 females. Twenty-nine females (30.8 +/- 4.4 years) were examined four days after vaginal delivery. Eleven of these 29 females were re-examined five months after vaginal delivery. Nineteen females (33.6 +/- 4.6 years) who were examined five to nine days after undergoing an elective cesarean section and 19 asymptomatic, nonpregnant females (26.8 +/- 6.9 years) served as controls. Motor latencies were bilaterally measured within the anal sphincter system at 5, 3.8, 2.6, and 1.5 cm from the perineal skin by using a concentric needle electrode after sacral magnetic stimulation. Means of the bilateral latencies were analyzed. RESULTS: In postpartum females who gave birth vaginally, motor latencies at 5 and 3.8 cm, although not those at 2.6 and 1.5 cm, from the perineal skin were significantly prolonged, and anal pressure monitored by maximum resting and squeeze pressures was significantly decreased compared with that in control females. The decreased anal pressure normalized spontaneously. The prolonged motor latencies at the upper two levels of the anal sphincter system persisted in these females for five months after vaginal delivery. CONCLUSIONS: The disturbance of innervation of the upper anal sphincter system after vaginal delivery may last for a long time, whereas the decreased anal pressure normalizes in a short time. The protracted disturbance of innervation of the upper anal sphincter system may be associated with later development of fecal incontinence.

Malignant struma ovarii with thyrotoxicosis.

BACKGROUND: Malignant struma ovarii is seldom diagnosed preoperatively due to the rarity of the disease itself and the even rarer complications of thyrotoxicosis. CASE: A 48-year-old woman presented with symptoms of hyperthyroidism and a pelvic tumor raising the possibility of ovarian malignancy. Hormonal findings revealed increased thyroid function, but the thyroid gland was normal in size and texture. Thus, she was diagnosed preoperatively as having a hormone-producing malignant struma ovarii. At surgery, a FIGO stage Ia ovarian papillary adenocarcinoma of the thyroid was found. An immunohistochemical tumor stain for thyroglobulin was positive and the ovarian venous thyroglobulin level was extremely high. Findings of hyperthyroidism disappeared over several weeks. CONCLUSION: Malignant struma ovarii can be diagnosed preoperatively. Complications of thyrotoxicosis should be kept in mind when evaluating an ovarian tumor.

3-Amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) induces caspase-dependent apoptosis in mononuclear cells.

3-Amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), one of the tryptophan pyrolysates, is a dietary carcinogen and is formed in cooked meat and fish in our daily diet. Trp-P-1 will affect the cells in the blood circulation system before it causes carcinogenicity in target organs such as the liver. In this study, the cytotoxicity of Trp-P-1 was investigated in mononuclear cells (MNCs) from blood. Trp-P-1 (10-15 microM) decreased cell viability and induced apoptosis characterized both by morphological changes and by DNA fragmentation 4 h after treatment. DNA fragmentation was also observed following treatment at 1 nM after 24 h in culture. This result suggested that apoptosis would occur in the body following unexpected intake of foods containing Trp-P-1. To determine the mechanism of apoptosis, we investigated the activation of the caspase cascade in MNCs. Trp-P-1 (10-15 microM) activated the caspase cascade, i.e. the activity of caspase-3, -6, -7, -8 and -9 increased dose-dependently using peptide substrates, the active forms of caspase-3, -8 and -9 were detected by immunoblotting, and cleavage of poly(ADP-ribose) polymerase and protein kinase C-delta as the intracellular substrates for caspases was observed. A peptide inhibitor of caspase-8 completely suppressed activation of all other caspases, while an inhibitor of caspase-9 did not. These results indicated that caspase-8 may act as an apical caspase in the Trp-P-1-activated cascade.

DNA-damaging carcinogen 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) induces apoptosis via caspase-9 in primary cultured rat hepatocytes.

The mechanism of cytotoxicity induced by the DNA-damaging carcinogen 3-amino-1,4-dimethyl-5H-pyrido[4,3-b] indole (Trp-P-1) was investigated in primary cultured rat hepatocytes. Cytotoxicity was caused by intact Trp-P-1 and not by metabolically activated derivatives prepared using a recombinant yeast strain AH22/pAMR2 expressing rat cytochrome P450 1A1, and not by metabolically activated derivatives. We also found internucleosomal DNA fragmentation 6 h after treatment with 30 microM Trp-P-1, indicating that the cytotoxicity was due to the induction of apoptosis. After treatment with Trp-P-1, c-Myc protein level increased in a time-dependent manner and p53 protein also increased transiently with a subsequent increase in Bax protein level. This apoptotic pathway required the activation of caspase-9 as an initiator after leakage of cytochrome c into the cytosol from mitochondria and the activation of caspase-3 and -7 as executioners, but not caspase-1, -6 or -8 as measured using the corresponding peptide inhibitors and substrates or western blotting. The activated caspases in turn cleaved poly(ADP-ribose) polymerase as an intracellular substrate. Furthermore, we detected NUC18-like endonuclease activity during apoptosis induced by Trp-P-1. These findings suggest that this apoptosis may have a role against heterocyclic amine-type carcinogens in normal cells.

Detection of human papillomavirus DNA in primary and metastatic lesions of carcinoma of the cervix in women from Okinawa, Japan.

Of 351 patients with invasive cervical cancer treated at Ryukyu University Hospital, Okinawa, 293 who were tested for human papilloma virus (HPV) DNA of the primary cervical lesion before the initiation of treatment were considered for the study. The polymerase chain reaction (PCR) was performed using fresh specimens, immediately after sampling. In 250 of 293 patients (85.3%), HPV DNA was detected in cervical tumor by PCR using L1 consensus primer. The positive rate by histology was 89.9% in squamous cell carcinoma, 93.8% in adenosquamous carcinoma, and 51.4% in adenocarcinoma. The former two figures were significantly higher than the latter (p < 0.001 and p = 0.002). Concerning identification of HPV types, HPV 16 was most predominant in squamous cell carcinoma, whereas type 18 was relatively high in adenocarcinoma. However, the type distribution of HPV was different to some extent from those in other countries. During treatment, 489 nodal and other tissue samples were obtained from 113 of 250 HPV DNA-positive patients, and were submitted to an assay of HPV DNA. HPV DNA was amplified in all 55 metastatic samples and also in 12 of 434 nonmetastatic tissues (2.8%). HPV types specified in these samples were always identical with the HPV types determined in their primary tumors. In 154 samples from 29 of 43 HPV DNA-negative patients, HPV DNA was not detected, either in 14 metastatic samples or in 140 histologically benign samples. Cancer-free, but HPV DNA-positive nodal, liver, and pulmonary tissues could be interpreted to be already involved at the time of examination, by observing the clinical course of the disease over time.

Clearance of antiphospholipid antibodies in pregnancies treated with heparin.

OBJECTIVE: To describe the natural history of serum antiphospholipid antibodies (lupus anticoagulant and anticardiolipin antibodies) in pregnant women treated with heparin, and to identify a possible association between changes in antibody status and outcomes of subsequent pregnancies. METHODS: Thirty-six women with antiphospholipid antibodies who had three or more repeated miscarriages were enrolled. Intravenous heparin was used for each of the first pregnancies after referral. Changes in antibody status were investigated with relation to outcomes of the index and subsequent pregnancies. RESULTS: Eighteen of 23 pregnancies in 36 antibody-positive women treated with heparin resulted in term or preterm deliveries with live-born infants, and five ended in abortions. Antibodies cleared in ten of 12 term pregnancies, in five of six preterm pregnancies, and in one of five abortions. There was a statistically significant difference between the term pregnancy and abortion groups (P <.05). Eleven second and third pregnancies in nine women in whom antibodies cleared resulted in term or preterm deliveries of live-born infants, without heparin therapy. The second and third pregnancies in one woman whose antibodies persisted ended in miscarriages despite repeated heparin administration. CONCLUSION: Antiphospholipid antibodies cleared spontaneously in some pregnant women treated with heparin. Subsequent pregnancies among women in whom antibodies cleared were managed successfully without medication, whereas pregnancies in women with persistent antibodies required treatment.

Multiple colorectal cancers in the elderly: a retrospective study of both surgical and autopsy cases.

BACKGROUND: Multiple primary cancers are not rare events in the large intestine, and account for approximately 5-7% of patients with colorectal cancer (CRC). There are few reports demonstrating clinicopathologic features of multiple CRCs in the elderly. METHODS: We clinicopathologically investigated 947 surgical patients and 362 autopsy samples from patients aged 65 years or more with CRC, including 81 surgical and 34 autopsy cases of multiple CRCs. We compared the data in the very old group (age > or = 85 years) with those of the younger age groups, i.e., a young-old group (65-74 years) and a middle-old group (75-84 years). RESULTS: The proportion of multiple CRCs was 8.6% (81/947) in the surgical patients and 9.4% (34/362) in the autopsy cases, with no significant difference among the three age groups. Similar site distributions and sex ratios, indicating proximal shift and female predominance with advancing age, were found in multiple and single CRCs, except for autopsy cases with multiple CRCs. Multiple CRCs in nonadjacent segments of the large intestine accounted for 11% (9/81) in surgical cases and 35% (12/34) in autopsy cases. In autopsy cases, the incidence of extracolorectal malignancies in patients with a single CRC was 22% (17/76) in the young-old group, 27% (39/147) in the middle-old group, and 35% (37/105) in the very old group, whereas the incidences in patients with multiple CRCs were 25% (1/4), 11% (2/18), and 50% (6/12), respectively. Regarding the organs with extracolorectal malignancies, the stomach (29%) was most frequent, followed by lung (14%), hematopoietic system (12%), and pancreatobiliary system (10%). CONCLUSIONS: These results indicate that the incidence of multiple CRCs in elderly patients with CRC is approximately 8%-10%, with no age-related difference, while extracolorectal malignancies increase with advancing age.

Combined effects of meropenem and aminoglycosides on Pseudomonas aeruginosa in vitro.

To investigate combinations of antibiotics against Pseudomonas aeruginosa, the in vitro effects of combinations of meropenem with each of three aminoglycosides, arbekacin, amikacin and netilmicin, were evaluated using an agar dilution chequerboard technique. The combinations of meropenem and aminoglycosides were effective against almost all P. aeruginosa strains tested, which included meropenem-resistant strains. Increased synergic effects were observed in combinations that included arbekacin or amikacin. None of the combinations had an antagonistic effect. Most of the synergic and additive effects were achieved at clinically relevant concentrations.