Restoration of innate and adaptive immune responses by HCV viral inhibition with an induction approach using natural interferon-beta in chronic hepatitis C.

Chronic hepatitis C (CHC) is a serious medical problem necessitating more effective treatment. This study investigated the hypothesis that an induction approach with nIFN-beta for 24 weeks followed by PEG-IFN-alpha+ribavirin (standard of care: SOC) for 48 weeks (novel combination treatment: NCT) would increase the initial virologic response rate and restore innate and adaptive immune responses in CHC. Seven CHC patients with a high viral load and genotype 1b were treated with NCT. Serum cytokine and chemokine levels were evaluated during NCT. NCT prevented viral escape and breakthrough resulting in persistent viral clearance of HCVRNA. IL-15 was increased at the end of induction therapy in both early virologic responders (EAVRs) and late virologic responders (LAVRs); CXCL-8, CXCL-10, and CCL-4 levels were significantly decreased (P < 0.05) in EAVR but not in LAVR during NCT, and IL-12 increased significantly (P < 0.05) and CXCL-8 decreased significantly (P < 0.05) after the end of NCT in EAVR but not in LAVR. NCT prevented viral breakthrough with viral clearance leading to improvement of innate and adaptive immunity resulting in a sustained virologic response (SVR). NCT (n = 8) achieved a higher SVR rate than SOC (n = 8) in difficult-to-treat CHC patients with genotype 1 and high viral loads.

The fixed herbal drug composition "Saikokaryukotsuboreito" prevents bone loss with an association of serum IL-6 reductions in ovariectomized mice model.

PURPOSE: Saikokaryukotsuboreito (SRB) is a traditional Japanese herbal medicine that has been used to treat hyperlipidemia. As some studies have shown that lipid-lowering drugs reduce osteoporosis, we investigated the effect of SRB on bone metabolism in the postmenopausal period using an ovariectomized (OVX) murine model. MATERIAL AND METHODS: Fifteen aged 9 weeks female mice were divided into three groups (n=5 each). The OVX group and SRB group underwent bilateral ovariectomy, after which the OVX group was fed a normal diet and the SRB group fed a normal diet containing 2% SRB. The sham group underwent sham surgery and was then fed a normal diet. Eight weeks after surgery, all mice were sacrificed, and bone volume, bone histomorphometric parameters, and bone-associated phenotype were compared among the groups. RESULTS: Compared with the OVX group, the SRB group showed suppression of bone volume loss at the tibia (SRB group: 12.7+/-0.7%, OVX group: 9.8+/-0.4%; p=0.005, ANOVA) and lumbar spine (SRB group: 15.1+/-0.9%, OVX group: 11.3+/-0.1%; p=0.031, ANOVA). A significant decrease in eroded surface was also observed in SRB-treated ovariectomized mice compared with the OVX group (p=0.022, ANOVA). We also found that serum levels of interleukin (IL)-6, a primary mediator of bone resorption, in the SRB group were significantly lower than in the OVX group (SRB: 52.5+/-6.8pg/ml; OVX: 138.0+/-23.1pg/ml; p=0.011, ANOVA). However, unexpectedly, SRB did not affect estradiol and total cholesterol in ovariectomized mice. CONCLUSION: SRB can prevent loss of bone volume and suppress serum IL-6 levels in this postmenopausal model and is a promising candidate for treatment of postmenopausal osteoporosis.

Juzentaihoto (TJ-48), a traditional Japanese herbal medicine, influences hemoglobin recovery during preoperative autologous blood donation and after hip surgery.

OBJECTIVE: Preoperative autologous blood donation is a widely used alternative to allogenic transfusion in hip surgery. However, it has been reported that autologous blood donation may induce preoperative anemia. Juzentaihoto (TJ-48) (Tsumura Co., Tokyo, Japan) is a Japanese herbal medicine that has been used to alleviate anemia. We investigated the effect of TJ-48 on anemia in the perioperative period. PATIENTS AND METHODS: 18 hips of 18 female patients who underwent total hip arthroplasty or rotational acetabular osteotomy (RAO) were divided into two groups. Group A consisted of 9 hips of 9 patients who were treated with TJ-48 at a dose of 7.5 g per day from 21 days before surgery to the day before surgery. Group B consisted of 9 hips of 9 patients who did not take TJ-48. Preoperative autologous blood donation was performed 21, 14 and 7 days before surgery. All patients deposited 400 ml each time for a total of 1,200 ml. Hemoglobin level was recorded on preoperative Days 21, 14 and 7 and postoperative Days 1, 4, 7 and 14. RESULTS: During the preoperative period, repeated measures ANOVA showed a significant difference between the two groups in hemoglobin level (p = 0.04). Despite the lack of TJ-48 after surgery, the rate of hemoglobin decline in Group A was less than in Group B at all examination times. No patients with TJ-48 experienced side effects, including gastrointestinal symptoms and unusual laboratory data. CONCLUSION: TJ-48 is useful for treating anemia during preoperative autologous donation.

Chemotherapy-induced neutropenia as a prognostic factor in advanced non-small-cell lung cancer: results from Japan Multinational Trial Organization LC00-03.

BACKGROUND: Neutropenia is a common adverse reaction of chemotherapy. We assessed whether chemotherapy-induced neutropenia could be a predictor of survival for patients with non-small-cell lung cancer (NSCLC). METHODS: A total of 387 chemotherapy-naïve patients who received chemotherapy (vinorelbine and gemcitabine followed by docetaxel, or paclitaxel and carboplatin) in a randomised controlled trial were evaluated. The proportional-hazards regression model was used to examine the effects of chemotherapy-induced neutropenia and tumour response on overall survival. Landmark analysis was used to lessen the bias of more severe neutropenia resulting from more treatment cycles allowed by longer survival, whereby patients who died within 126 days of starting chemotherapy were excluded. RESULTS: The adjusted hazard ratios for patients with grade-1 to 2 neutropenia or grade-3 to 4 neutropenia compared with no neutropenia were 0.59 (95% confidence interval (CI), 0.36-0.97) and 0.71 (95% CI, 0.49-1.03), respectively. The hazard ratios did not differ significantly between the patients who developed neutropenia with stable disease (SD), and those who lacked neutropenia with partial response (PR). CONCLUSION: Chemotherapy-induced neutropenia is a predictor of better survival for patients with advanced NSCLC. Prospective randomised trials of early-dose increases guided by chemotherapy-induced toxicities are warranted.

Alcoholic fermentation and its prevention by Lactobacillus buchneri in whole crop rice silage.

AIMS: To evaluate the fermentation characteristics and the effects of Lactobacillus buchneri inoculation in ensiling whole crop rice. METHODS AND RESULTS: Laboratory-scale silages were prepared from whole crop rice harvested at yellow-ripe stage. The crop was ensiled for 2 months with and without inoculation of L. buchneri at 10(4), 10(5) and 10(6) CFU g(-1). The effect of prolonged ensiling was also studied by using the same crop; the silos were opened at 1, 3, 6 and 12 months, while the inoculation was made at 10(5) CFU g(-1). Enhanced alcoholic fermentation was found in untreated silage; the sum of ethanol and 2,3-butanediol were seven times higher at 2 months than those of lactic and volatile fatty acids, while the differences were diminished at 12 months owing to the reduction of ethanol in the late ensiling period. Inoculation of L. buchneri inhibited the alcohols; however, ethanol yet prevailed over the fermentation until 6 months, after which acetic acid became the main product in the inoculated silage. Regardless of inoculation and ensiling period, yeasts were not found in whole crop rice silage. CONCLUSIONS: Substantial amounts of ethanol and 2,3-butanediol would be produced in silage prepared from whole crop rice. The alcoholic fermentation can be suppressed when inoculated with L. buchneri. SIGNIFICANCE AND IMPACT OF THE STUDY: Inoculation of L. buchneri could be an option to prevent ethanol fermentation in silage.

Therapeutic effects of Saireito (TJ-114), a traditional Japanese herbal medicine, on postoperative edema and inflammation after total hip arthroplasty.

Saireito (TJ-114) is a traditional Japanese herbal medicine that has been used for treating edema and inflammation in diseases such as nephritic disease. This study investigates the effect of TJ-114 on postoperative edema and inflammation after total hip arthroplasty (THA). Patients who underwent cementless THA were randomly divided into two groups: Group A consisted of 8 hips of 8 patients who were treated with TJ-114 at a dose of 9 g/day 2 days before surgery and for 2 weeks after surgery; Group B consisted of 9 hips of 9 patients who did not take TJ-114. Although no significant difference was observed between the two groups for lower extremity edema, it was found that swelling of the proximal leg in Group A was less than that in Group B. Furthermore, 3 weeks after surgery, every measuring point in the lower extremity showed that TJ-114 tended to decrease postoperative swelling compared to measurements of swelling of patients who did not take TJ-114. Serum C-reactive protein (CRP) levels of 6 out of 8 patients in Group A decreased and became negative 2 weeks after surgery; however, there were no patients in Group B whose CRP levels became negative after 2 weeks. In conclusion, TJ-114 is safe and useful for the prevention and early recovery of postoperative leg edema after THA with an association of rapid CRP reduction.

Adolescents' attachment style and early experiences: a gender difference.

We examined gender differences in perceived rearing and adult attachment style in adolescents. A total of 3,912 senior college students (1,149 men and 2,763 women) ages 18-23 (men's M = 20.1 years, women's M = 20.0 years) were administered a set of questionnaires including Relationship Questionnaire (to measure adult attachment), the Parental Bonding Instrument (perceived rearing), and a list of early life events. In the men, positive adult total attachment style was predicted by the scores of paternal care and low scores on maternal overprotection in a hierarchical regression analysis. On the other hand, in the women, positive adult total attachment style was predicted by the scores of paternal and maternal care, and low score on maternal overprotection. Adult attachment was also predicted by fewer Peer Victimization experience as a child in both men and women. However, while men's adult attachment was predicted by Self Disease experiences, women's adult attachment was predicted by Top Star experiences and fewer Relocation experiences. The adult attachment style was predictable from early experiences but there existed some gender differences.

Linear IgA bullous dermatosis of neonatal onset: case report and review of the literature.

UNLABELLED: Several small blisters were noticed on the forehead and the trunk of a newborn boy on day 1. The blisters gradually enlarged and spread over the whole body including the oral mucosa. A skin biopsy was performed twice and subepidermal bullae with polymorphonuclear and mononuclear cell infiltration were demonstrated. Direct immunofluorescence showed linear IgA, IgG and C3 depositions along the basement membrane zone and this finding led to a diagnosis of linear IgA bullous dermatosis. So far, internationally, only one case has ever been reported on the disease at neonatal onset. The skin lesions spontaneously regressed and the mucosal lesions were controlled with diaminodiphenylsulfone. CONCLUSION: In neonates with prolonged blistering, autoimmune disease such as linear IgA bullous dermatosis should be considered within the differential diagnosis and an immunofluorescence study must be performed.

Preservation of the bone mineral density of the femur after surface replacement of the hip.

We investigated the effect of the Birmingham hip resurfacing (BHR) arthroplasty on the bone mineral density (BMD) of the femur. A comparative study was carried out on 26 hips in 25 patients. Group A consisted of 13 patients (13 hips) who had undergone resurfacing hip arthroplasty with the BHR system and group B of 12 patients (13 hips) who had had cementless total hip arthroplasty with a proximal circumferential plasma-spray titanium-coated anatomic Ti6A14V stem. Patients were matched for gender, state of disease and age at the time of surgery. The periprosthetic BMD of the femur was measured using dual-energy x-ray absorptiomentry of the Gruen zones at two years in patients in groups A and B. The median values of the BMD in zones 1 and 7 were 99% and 111%, respectively. The post-operative loss of the BMD in the proximal femur was significantly greater in group B than in group A. These findings show that the BHR system preserves the bone stock of the proximal femur after surgery.

Small intestinal metastasis from renal cell carcinoma exhibiting rare findings.

Small intestinal metastasis from renal cell carcinoma (RCC) has only rarely been described. We report two patients who developed small bowel metastases from RCC showing different clinicopathological characteristics. Both patients underwent hemilateral nephrectomy for RCC and developed lung metastases metachronously or simultaneously. One patient developed occlusive ileus caused by multiple polypoid tumours composed of sarcomatoid tissue in the jejunum shortly after nephrectomy. The other patient presented melaena due to bleeding from a Borrmann 2-like tumour in the jejunum six years after nephrectomy. Clinically, his disease was slow-growing. Sarcomatoid histology and Borrmann 2-like tumour in this report are rare findings in metastatic tumour of RCC in the small bowel.

Quantitative changes in nuclear pores and chromatoid bodies induced by neuropeptides during cell differentiation in the planarian Dugesia japonica.

Neuropeptides were used in experiments to assess their effects on planarian cells. Intact and decapitated planarians exposed to 10(-6) M neuropeptides for two days were examined electron microscopically and quantitative changes in the nuclear pores and chromatoid bodies in various types of cells were ascertained. The data clearly indicated the diversity of effects produced in planarian cells by neuropeptide treatments. The number of nuclear pores increased considerably in each cell type treated with neuropeptides. In particular, the effects of neuropeptides were strongest in differentiating cells which were forming the regeneration blastema. Neuropeptide-treated cells also experienced a dramatic increase in the number of chromatoid bodies. The results obtained in this study suggest that synthesis of RNAs leading to increases in the numbers of nuclear pores and chromatoid bodies is facilitated in neuropeptide-treated cells which are undergoing cell differentiation. The different mechanisms of the effects induced in undifferentiated cells by neuropeptides are discussed.

Anxiety in Japanese women after elective abortion.

OBJECTIVE: To examine women's anxiety levels after elective abortion. DESIGN AND SETTING: Women seeking elective abortion at six clinics in Japan were solicited to participate in a questionnaire survey. PARTICIPANTS: Sixty-six Japanese women requesting abortion participated in this survey. MAIN OUTCOME MEASURES: State anxiety was measured using Spielberger's State Trait Anxiety Inventory before and after abortion. RESULTS: Multiple regression analyses using predictor variables with a significant link to postabortion anxiety level showed that among potential predictors, a conservative attitude toward abortion was the most significant predictor of postabortion anxiety after controlling for the level of preabortion anxiety. CONCLUSION: These findings suggest that a woman's attitude toward abortion and reproductive rights is an important but neglected factor influencing postelective abortion anxiety. Medical and nursing professionals should, therefore, take note of a woman's attitude toward abortion as a part of her mental health care.

SEA0400, a novel and selective inhibitor of the Na+-Ca2+ exchanger, attenuates reperfusion injury in the in vitro and in vivo cerebral ischemic models.

The effect of the newly synthesized compound 2-[4-[(2,5-difluorophenyl)methoxy]phenoxy]-5-ethoxyaniline (SEA0400) on the Na+-Ca2+ exchanger (NCX) was investigated and compared against that of 2-[2-[4-(4-nitrobenzyloxy)phenyl]ethyl]isothiourea (KB-R7943). In addition, the effects of SEA0400 on reperfusion injury in vitro and in vivo were examined. SEA0400 was extremely more potent than KB-R7943 in inhibiting Na+-dependent Ca2+ uptake in cultured neurons, astrocytes, and microglia: IC50s of SEA0400 and KB-R7943 were 5 to 33 nM and 2 to 4 microM, respectively. SEA0400 at the concentration range that inhibited NCX exhibited negligible affinities for the Ca2+ channels, Na+ channels, K+ channels, norepinephrine transporter, and 14 receptors, and did not affect the activities of the Na+/H+ exchanger, Na+,K+-ATPase, Ca2+-ATPase, and five enzymes. SEA0400, unlike KB-R7943, did not inhibit the store-operated Ca2+ entry in cultured astrocytes. SEA0400 attenuated dose- dependently paradoxical Ca2+ challenge-induced production of reactive oxygen species, DNA ladder formation, and nuclear condensation in cultured astrocytes, whereas it did not affect thapsigargin-induced cell injury. Furthermore, administration of SEA0400 reduced infarct volumes after a transient middle cerebral artery occlusion in rat cerebral cortex and striatum. These results indicate that SEA0400 is the most potent and selective inhibitor of NCX, and suggest that the compound may exert protective effects on postischemic brain damage.

Full weight-bearing after cementless total hip arthroplasty.

In a prospective study of cementless total hip arthroplasty, 19 hips in 17 patients (Group A) were allowed full weight-bearing immediately after the operation while 18 hips in 16 patients (Group B) were first allowed weight-bearing after 6 weeks. Patients were matched for sex, age at surgery, height, weight, and follow-up period and there were no significant differences in hip scores between the two groups. Rehabilitation to gain walking ability with a cane lasted 5.8 days for Group A and 44.8 days for Group B (P = 0.0001). The hospital stay after surgery was 30.1 days for Group A and 46.7 days for Group B (P = 0.006). All patients showed bone ingrowth radiographically. There were no complications in either group.

Gastric cancer with Virchow's and multiple lung metastases showing a remarkable response to preoperative chemotherapy: report of a case.

We report herein a rare case with advanced gastric cancer combined with group 4 lymph node and lung metastases that responded remarkably to neoadjuvant chemotherapy. A 65-year-old man was found to have a well-differentiated type 3 gastric cancer that invaded the duodenum locally and was accompanied with Virchow's, para-aortic lymph nodes, and multiple lung metastases based on physical, endoscopic, and radiological examinations. In addition, his carbohydrate antigen (CA) 19-9 was elevated to 3965U/ml, and CA72-4 to 46U/ml. Prior to surgery, he was treated with 5-fluorouracil (5-FU; 500mg/body per day) and low-dose cisplatinum (CDDP; 10mg/body per day) as neoadjuvant chemotherapy for 6 weeks. As a result, a partial response was obtained in all lesions, and CA19-9 and CA72-4 decreased to 463U/ml and 9.4U/ml, respectively. Four weeks after the completion of neoadjuvant chemotherapy, a distal gastrectomy was performed, and a histopathological examination of the resected specimen showed a grade 2 response to chemotherapy. Immunohistochemically, the thymidylate synthase expression level was very low in the tumor tissues, which might account for the good response to the combination chemotherapy with 5-FU and CDDP observed in the present case.

Complete genomic sequence of the filamentous nitrogen-fixing cyanobacterium Anabaena sp. strain PCC 7120.

The nucleotide sequence of the entire genome of a filamentous cyanobacterium, Anabaena sp. strain PCC 7120, was determined. The genome of Anabaena consisted of a single chromosome (6,413,771 bp) and six plasmids, designated pCC7120alpha (408,101 bp), pCC7120beta (186,614 bp), pCC7120gamma (101,965 bp), pCC7120delta (55,414 bp), pCC7120epsilon (40,340 bp), and pCC7120zeta (5,584 bp). The chromosome bears 5368 potential protein-encoding genes, four sets of rRNA genes, 48 tRNA genes representing 42 tRNA species, and 4 genes for small structural RNAs. The predicted products of 45% of the potential protein-encoding genes showed sequence similarity to known and predicted proteins of known function, and 27% to translated products of hypothetical genes. The remaining 28% lacked significant similarity to genes for known and predicted proteins in the public DNA databases. More than 60 genes involved in various processes of heterocyst formation and nitrogen fixation were assigned to the chromosome based on their similarity to the reported genes. One hundred and ninety-five genes coding for components of two-component signal transduction systems, nearly 2.5 times as many as those in Synechocystis sp. PCC 6803, were identified on the chromosome. Only 37% of the Anabaena genes showed significant sequence similarity to those of Synechocystis, indicating a high degree of divergence of the gene information between the two cyanobacterial strains.

Complete genome structure of the nitrogen-fixing symbiotic bacterium Mesorhizobium loti.

The complete nucleotide sequence of the genome of a symbiotic bacterium Mesorhizobium loti strain MAFF303099 was determined. The genome of M. loti consisted of a single chromosome (7,036,071 bp) and two plasmids, designated as pMLa (351,911 bp) and pMLb (208, 315 bp). The chromosome comprises 6752 potential protein-coding genes, two sets of rRNA genes and 50 tRNA genes representing 47 tRNA species. Fifty-four percent of the potential protein genes showed sequence similarity to genes of known function, 21% to hypothetical genes, and the remaining 25% had no apparent similarity to reported genes. A 611-kb DNA segment, a highly probable candidate of a symbiotic island, was identified, and 30 genes for nitrogen fixation and 24 genes for nodulation were assigned in this region. Codon usage analysis suggested that the symbiotic island as well as the plasmids originated and were transmitted from other genetic systems. The genomes of two plasmids, pMLa and pMLb, contained 320 and 209 potential protein-coding genes, respectively, for a variety of biological functions. These include genes for the ABC-transporter system, phosphate assimilation, two-component system, DNA replication and conjugation, but only one gene for nodulation was identified.