Antimetastatic Activity of Polymeric RGDT Peptides Conjugated with Poly(ethylene glycol)

Polymeric peptides containing defined repetitive or cyclic structures of RGDT sequence, (RGDT)_n (n = 1 to 11) and cyclo(RGDT)_n (n=2 to 4), at a dose of 500 μg exhibited an inhibitory effect on experimental lung metastasis upon co-injection with tumor cells and the magnitude of the effect increased in parallel with the increase of degree of repetition of the RGDT sequence. The conjugation of (RGDT)_n (n = 1, 5, 11) with poly(ethylene glycol), PEG as a polymeric carrier led to enhanced inhibition of lung metastasis in proportion to the degree of RGDT sequence repetition and in a dose-dependent manner. Multiple i.v. administrations of PEG-(RGDT)₁₁, at 2-day and 3-day intervals before the excision of primary tumors, effectively inhibited spontaneous lung metastasis by s.c. inoculation of tumors, whereas (RGDT)₁₁ exhibited inhibition of lung metastasis only when given at 2-day intervals. This indicates that the conjugation of PEG with (RGDT)_n allowed the prolongation of administration interval, implying a sustained inhibitory effect on tumor metastasis. In support of this supposition, a decrease in the arrest of radiolabeled tumor cells in the lungs was observed when PEG-(RGDT)₁₁ was co-injected i.v. with tumor cells, or injected i.v. one day before tumor inoculation. In contrast, (RGDT)₁₁ significantly inhibited the tumor cell arrest in the lungs only upon co-injection with tumor cells. We also noted that (RGDT)_n, cyclo(RGDT)_n and PEG-(RGDT)₁₁ inhibited tumor cell invasion into Matrigel in a concentration-dependent manner and in proportion to the degree of RGDT sequence repetition, indicating that the peptide-mediated antimetastatic effect is partly associated with the anti-invasive potential. Thus, the conjugation of anti-cell adhesive and antimetastatic RGDT peptide with PEG might provide a therapeutically promising basis for the prevention of cancer metastasis (“anti adhesion therapy”).     

The effects of personal relationships on facial displays

Previous studies have suggested that facial displays in the presence of others are influenced by the relationship with accompanying persons. In these studies, subjects participated with friends or strangers, without any focus on social interactions between partners. In the current study, pairs of friends or strangers viewed film clips expected to elicit positive and negative affects; the control group participated without partners. We measured synchronous smiles between partners as a social interactive display, in addition to the duration and the frequency of smiles and frowns. Subjective emotion and social motive were also measured. Smiles were facilitated by the presence of a friend than a stranger or the condition of lone participation, regardless of stimulus valence. Synchronous smiles and the communication motive were also enhanced with a friend than with a stranger. These results suggested that the expression of smiles was facilitated by the communication motive and social interactions between partners.     

Effects of Bakumondo-to (Mai-Men-Dong-Tang) on cough sensitivity to capsaicin in asthmatic patients with cough hypersensitivity]

Some patients with bronchial asthma have increased cough sensitivity. In such patients coughing may be an inducer of wheeze. The aim of the present study was to investigate the effect of Bakumondo-to on the cough sensitivity and respiratory tract inflammation in asthmatic patients with increased cough sensitivity. In addition influences of intensity of respiratory tract inflammation, gender, type of asthma, and disease period on the effect of Bakumondo-to on the cough sensitivity were examined. Twenty-one bronchial asthmatics whose cough thresholds to capsaicin were less than 3.9 microM were examined. METHODS: Cough thresholds to capsaicin (concentration of inhaled capsaicin solution causing 5 or more coughs) was measured before and after 2 months or more treatment with Bakumondo-to (9 g/day, TJ-29). Number of eosinophils in peripheral blood, sputum eosinophil ratio, and ECP level in the serum were also measured before and after treatment. RESULTS: Bakumondo-to significantly increased the cough threshold. Although respiratory tract inflammation was not significantly improved, number of eosinophils in peripheral blood, sputum eosinophil ratio and ECP level in the serum were remarkably decreased more than the half. And Bakumondo-to was more effective in asthmatic subjects with severe airway inflammation. Furthermore, a greater effect of it was observed in women. A greater effect was also observed in patients having a disease duration of less than 1 year. CONCLUSION: Our results suggest that Bakumondo-to may be an effective therapeutic preparation for coughing in asthmatic patients with cough hypersensitivity.     

Histological examination of beta-tricalcium phosphate graft in human femur

Prominent osteoconductive activity and the biodegradable nature of beta tricalcium phosphate (beta-TCP) for bone grafts in animal experiments has been reported. A new type of beta-TCP has been manufactured at extraordinarily high purity and has been available as potent bone grafting substitute for clinical use. The histological features of grafted beta-TCP in human bone have been analyzed. A 33-year-old female with a bone tumor of the proximal femur underwent curettage and beta-TCP graft under the diagnosis of probable benign fibrous dysplasia. Four weeks later, the proximal femur, including the grafted beta-TCP was resected because of the final diagnosis of the curettaged materials was osteosarcoma. The resected specimen revealed abundant direct new bone apposition on beta-TCP. There was no cartilaginous tissue or enchondral ossification. Bone formation was more prominent in the periphery of the grafted area than in the center. There was a considerable number of osteoclast-like giant cells surrounding the beta-TCP. This case illustrated that highly purified beta-TCP had prominent osteoconductive activity and biodegradable nature in human bone.     

Immunosuppressive effect of restraint stress on the initiation of allergic rhinitis in mice

BACKGROUND: Exposure to acute stressors modulates both innate and acquired immune function. However, little is known about whether stress has the potential to modulate the pathogenesis of allergic rhinitis. OBJECTIVES: To determine the effects of acute restraint stress on the initiation of allergic rhinitis in a murine model. METHODS: CBA/J mice were repeatedly intranasally sensitized with phospholipase A2 (PLA2) from honeybee venom without adjuvant. Restraint stress was applied using uniform cylinders once a week for a continuous 8-hour period, on five occasions in total. Production of PLA2-specific antibodies and degree of nasal and blood eosinophilia were compared between stressed and control mice. RESULTS: Repeated intranasal sensitization with PLA2 induced PLA2-specific IgE and marked eosinophilia in both the nose and blood in CBA/J mice. Exposure to restraint stress significantly inhibited production of PLA2-specific IgE, IgG1 and IgG2a. Conversely, the stress exerted no significant effect on eosinophilia. CONCLUSIONS: Exposure to acute restraint stress inhibits antigen-specific antibody production, but not local or systemic eosinophilia. The results of this study suggest that acute stress has the potential to modulate the initiation of allergic rhinitis.     

Case report of de novo dup(18p)/del(18q) and r(18) mosaicism

This is a report of a 27-year-old woman with an unusual de novo chromosomal abnormality. Mosaicism was identified in peripheral blood cells examined by standard G-bands by trypsin using Giemsa (GTG) analysis and fluorescence in situ hybridization (FISH) analysis with chromosome-18 region-specific probes, 46,XX,del(18)(pter → q21.33:)[41], 46,XX,r(18)(::p11.21 → q21.33::)[8], and 46,XX,der(18)(pter → q21.33::p11.21 → pter)[1]. On the other hand, the karyotype of periodontal ligament fibroblasts was nonmosaic, 46,XX, der(18)(pter → q21.33::p11.21 → pter)[50]. All cell lines appeared to be missing a portion of 18q (q21.33 → qter). The pattern of the dup(18p)/del(18q) in the rod configuration raises the possibility of an inversion in chromosome 18 in one of the parents. However, no chromosomal anomaly was detected in either parent. The most probable explanation is that de novo rod and ring configurations arose simultaneously from an intrachromosomal exchange. The unique phenotype of this patient, which included primary hypothyroidism and primary hypogonadism, is discussed in relation to her karyotype.     

The current method of handling of test samples and medical reimbursement for POCT in Japan

Point of care testing(POCT) is defined as clinical testing done at or near the site of patient treatment and care in the medical field, and includes all clinical test other than those performed at hospital laboratories and outside testing centers. Home testing is also a form of POCT relating to residential medical care. The ratio of clinical tests based on POCT has not tended to increase as rapidly in Japan, although such tests are greatly increasing in the US while clinical tests performed at hospital laboratories are decreasing. POCT products are generally applied to direct analysis of test samples obtained from patients. Since storage, transportation or pretreatment after sampling is not necessary in POCT, test data can be obtained in real time. Therefore, it is important to complete testing immediately after obtaining samples without transporting or storing them, when handling POCT samples. Consideration of POCT as a part of health care services covered by health insurance is the same as in the case of conventional testing. Recent technological innovation has provided a wide variety of POCT products that do not require medical equipment or reagents. Further development of novel, innovative POCT procedures in the near future is promising.     

Laboratory tests for infectious diseases and medical reimbursement

Emerging and reemerging infectious diseases, drug-resistant bacteria and nosocomial infection are becoming increasingly serious social problems. To control infectious diseases, it is important to develop effective therapies and to achieve complete prevention of pathogen transmission. For these purposes, rapid detection of pathogenic microorganisms is essential. Recent development and technical innovation in laboratory tests and diagnosis for infectious diseases are remarkable. New techniques such as antigen detection and genetic diagnosis, neither of which require conventional culture, have been intensively developed and introduced into clinical practice. These methods are now widely accepted as effective diagnostic tools because of their high specificity, high sensitivity and rapidity. In this article, we describe the burden of medical expenses under the law on novel infectious diseases and medical reimbursement for diagnostic tests for these diseases.