High molecular weight (HMW) kininogen is known to be a large plasma protein and cleaved by plasma proteinase kallikrein, then it generates four fragments in the blood coagulation cascade: heavy ...chain, bradykinin, fragment 1·2, and light chain. The fragment 1·2 has also been found in the basic protein fraction of bovine milk as a bioactive protein which promotes osteoblast proliferation. The milk basic protein has been shown to be a multi functional edible protein which promotes bone formation and inhibits bone resorption. In the present study, we purified the fragment 1·2 from bovine plasma and assessed it could promote osteoblast proliferation and posses the activity after pepsin digestion. Purified plasma HMW kininogen did not promote the proliferation, however, the kallikrein-cleaved HMW kininogen promoted the proliferation. The fragment 1·2, purified from the proteolysate, also promoted the proliferation. The pepsin digestion was performed according to the method of the assessment of allergenesity of genetically modified crops. After pepsin digestion, the fragment 1·2 generated resistant fragments and showed the promoting activity of osteoblast proliferation. These results suggest that the enzymatically-digested fragments of bovine HMW kininogen are able to be a naturally occurred active protein that promotes the bone formation by oral administration.
Milk has more beneficial effects on bone health compared to other food sources. Recent in vitro and in vivo studies showed that milk whey protein, especially its basic protein fraction, contains ...several components capable of both promoting bone formation and inhibiting bone resorption. However, the effects of milk basic protein (MBP) on bone metabolism of humans are not known. The object of this study was to examine the effects of MBP on bone metabolism of healthy adult women. Thirty-three normal healthy women were randomly assigned to treatment with either placebo or MBP (40 mg per day) for six months. The bone mineral density (BMD) of the left calcaneus of each subject was measured at the beginning of the study and after six months of treatment, by dual-energy x-ray absorptiometry. Serum and urine indices of bone metabolism were measured at the base line, three-month intervals, and the end of the study. Daily intake of nutrients was monitored by a three-day food record made at three and six months. The mean (±SD) rate of left calcaneus BMD gain of women in the MBP group (3.42±2.05%) was significantly higher than that of women in the placebo group (2.01±1.75%, P=0.042). As compared with the placebo group, urinary cross-linked N-teleopeptides of type-I collagen/creatinine and deoxypyridinoline/creatinine were significantly decreased in the MBP group (p<0.05), while no significant differences between the two groups were observed in serum osteocalcin and bone-specific alkaline phosphatase concentrations. A daily MBP supplementation of 40 mg in healthy adult women can significantly increase their BMD independent of dietary intake of minerals and vitamins. This increase in BMD might be primarily mediated through inhibition of osteoclast-mediated bone resorption by the MBP supplementation.
We studied the effects of daily intake of milk basic protein (MBP) on radial bone mineral density (BMD) in healthy adult women. Thirty-three healthy women were randomly assigned to a 6-month trial ...with either placebo or MBP (40 mg per day). The radial BMD of each volunteer was measured at the beginning of and at six months after the trial. The mean BMD value at the 6 th month in the MBP group increased significantly at both 1/6 and 1/10 portion from the distal end of the radius, whereas that in the control group did not. The BMD gain of each volunteer in the MBP group was significantly higher than that in the placebo group. Thus a daily MBP supplementation of 40 mg in healthy adult women can significantly increase radial BMD.
Purpose
To investigate the feasibility of accelerated partial breast irradiation (APBI) for Japanese patients, we started high-dose-rate interstitial brachytherapy (HDR-ISBT) as monotherapy after ...breast-conserving surgery (BCS).
Methods
We implanted 45 Tis-2 breast cancer patients at National Hospital Organization Osaka National Hospital between June 2002 and June 2006. Our eligibility criteria were broader than the ones used previously in western countries. We included margin-positive cases and younger patients (median age: 44; range: 26–68) to adapt the criteria for Japanese women. Total prescribed doses were 36–42 Gy in six to seven fractions, and the volumes encompassed by 100% prescribed dose (V100) were 38.5–315.1 cc. Fifteen patients received chemotherapy.
Results
Treatment could be completed for all patients. Two local failures (4%) and two distant metastases were observed, while one patient died of liver metastasis. Seven wound complications, four with and three without infection, and two rib fractures occurred. The significant risk factors for wound complications were non-administration of prophylactic antibiotics during ISBT (
P
< 0.01), open cavity implant (
P
< 0.05), large V100 (
P
< 0.01), V150 (
P
< 0.05), and V200 (
P
< 0.05).
Conclusion
APBI after BCS for Japanese women with relatively small breasts was well tolerated, but special care should be taken with treatment technique.
Patients with de novo stage IV and recurrent metastatic breast cancer are often treated with the same strategies, although the difference in prognostic outcomes remains unclear. The objective of this ...retrospective chart review study was to compare the prognostic outcomes between two types of patients with hormone receptor-positive (HR+), HER2-negative (HER2-) breast cancer.
We estimated overall survival of the two groups and evaluated the progressive course of the disease using disease-free interval (DFI) and interval from the end of adjuvant treatment to the first recurrence (AFI).
We studied 172 patients with HR+/HER2- breast cancer, of which 65 were de novo and 107 were recurrent. Median OS between de novo and recurrent BC was 4.85 and 3.45 years, respectively (p=0.046). Recurrent patients with a DFI<2 years were found to have a significantly poorer prognosis than recurrent patients with a DFI≥2 years (p=0.016) and de novo patients (p=0.002). Similarly, recurrent patients with an AFI<1 year had a significantly poorer prognosis compared to de novo patients (p=0.026).
De novo patients had better prognoses than recurrent patients with DFI<2 years or AFI<1 year, likely due to their therapy-naïve status or lower resistance to systemic treatment.
Kakkon-to is composed of seven medicinal herbs and exhibited novel antipyretic activity by suppressing interleukin-1
α production responsive to interferon in a murine intranasal influenza virus ...infection model. Using this model, antipyretic compounds with such novel biological activities were characterized from the herbs. The organic solvent-extractable fractions of
Cinnamomum cassia among the herbs showed antipyretic activity. We selected six antipyretic compounds from 48 cinnamyl derivatives and related compounds that may be mainly involved in the fractions. Their antipyretic activity was significantly correlated with interleukin-1
α regulatory activity. Four of them suppressed interleukin-1
α production to a basal level and showed different mode of antipyretic action from that of aspirin in interleukin-1
α-injected mice. Structure–bioactivity relationship of the four suggested that an ester bond played an important role for both antipyretic and interleukin-1
α regulatory activities. These compounds may be useful in analyzing interleukin-1
α-producing cells in fever production and the mechanism of defervescence by suppressing interferon-induced interleukin-1
α production.
Glycyrrhizin, a major component of a herb (licorice), has been intravenously used for the treatment of chronic hepatitis B in Japan and improves liver function with occasional complete recovery from ...hepatitis. This substance modifies the intracellular transport and suppresses sialylation of hepatitis B virus (HBV) surface antigen (HBsAg) in vitro. This study was designed to clarify the pharmacological basis for its effectiveness. The structure-bioactivity relationship of glycyrrhizin, glycyrrhetic acid 3-
O-monoglucuronide and glycyrrhetic acid was determined, and glycyrrhetic acid was found to be the most active of them. The amounts of three substances bound to the liver were evaluated in guinea pigs after intravenous administration of glycyrrhizin. Glycyrrhizin and glycyrrhetic acid 3-
O-monoglucuronide were detected at concentrations of 31.8-1.3 μg/g of liver, but glycyrrhetic acid was not detected. When glycyrrhizin attained these concentrations in the cellular fraction of the PLC/PRF/5 cell culture, it suppressed the secretion of HBsAg as reported previously. These results indicated that glycyrrhizin administered intravenously might bind to hepatocytes at the concentration at which glycyrrhizin could modify the expression of HBV-related antigens on the hepatocytes and suppress sialylation of HBsAg.
Kawasaki disease causes systemic vasculitis. The development of skin lesions at the vaccination site with Bacillus Calmette-Guérin (BCG) is an important diagnostic symptom. We hypothesized that ...infection with ubiquitous microorganisms immunogenically related to BCG might induce an immunopathologic reaction leading to the development of Kawasaki disease. Mice were first inoculated with BCG, and then secondarily inoculated 4 weeks later with crude extract from Mycobacterium intracellulare (cMI), an abundant atypical mycobacterium. Animals inoculated with BCG followed by cMI developed coronary arteritis with infiltration of inflammatory cells, whereas control animals inoculated with only cMI or BCG did not, suggesting that the immune response to the mycobacteria induced autoimmunity to the vascular wall. Intravenous injection with antibodies to peroxiredoxin II, a modulator of vascular remodeling and a suggested target for autoimmune vasculitis, also resulted in coronary arteritis, but only after prior inoculation with BCG. Tumor necrosis factor-α, MCP1 and interferon-γ production were significantly higher in the animals inoculated with BCG than in the control groups (P<0.05). BCG immunization was required for the development of coronary arteritis, suggesting that these cytokines might play important roles. The results indicate that BCG induces primary autoimmunity and stimulates cytokine induction, and that atypical mycobacterial infection boosts the autoimmunity resulting in coronary arteritis.
Carcinoma of an accessory mammary gland is an extremely rare tumor. A 61-year-old male patient presented with a hard mass measuring 85 mm × 51 mm in the left axilla. Incisional biopsy ...histopathologically showed an adenocarcinoma compatible with breast carcinoma originating in an accessory mammary gland. Systemic examinations revealed no evidence of malignant or occult primary lesion in the bilateral mammary glands or in other organs. Neoadjuvant chemotherapy was performed for the locally advanced axillary tumor and reduced the tumor to 55 mm in size, and, then, he could undergo complete resection with a negative surgical margin in combination with reconstructive surgery to fill the resulting skin defect with a local flap of the latissimus dorsi muscle. The patient has presented with no metastatic lesion in four years since the operation. This unusual case shows that neoadjuvant chemotherapy is an effective and tolerated therapy for advanced accessory breast cancer in the axilla.
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