Analysis of 605 tuberculosis outbreaks in Japan, 1993-2015: time, place and transmission site.

Since 1993, reports on tuberculosis (TB) outbreaks have been collected in Japan; however, there has never been an overall analysis of these TB outbreaks. We aim to provide one here. The TB outbreak data were obtained from the Ministry of Health, Labour and Welfare and are described in terms of time, place and transmission site. The average number of TB cases and latent tuberculosis infection (LTBI) were compared by the transmission site. Some 605 TB outbreaks with 3491 TB cases were reported in 1993-2015 with an increasing trend (r = 0.45), during which time 728 777 TB cases were reported nationwide. On an average, TB outbreaks occurred more often in April to May (5.5 outbreaks per 2 months) than in December to January (3.4). The most common transmission sites were workplaces (n = 255), followed by health facilities (n = 144), schools (n = 60) and welfare facilities (n = 48). Psychiatric hospitals and nursing homes had the highest average number of TB cases per outbreak (8.5 each), whereas schools and prisons had the highest numbers of LTBI cases (29.1 and 38.9, respectively). Countries, particularly those that have resources to investigate TB outbreaks, should collect and analyse findings of TB outbreaks, as it informs surveillance systems and eventually strengthens general health systems.

Anatomic double bundle ACL reconstruction outperforms any types of single bundle ACL reconstructions in controlling dynamic rotational laxity.

PURPOSE: To compare the different types of ACL reconstructions in terms of knee dynamic laxity evaluated by acceleration. METHODS: Sixteen fresh frozen cadaveric knees were used. Pivot shift test was manually performed while monitoring the tibial acceleration by use of a triaxial accelerometer. The test was repeated before and after the ACL resection and reconstruction. Three types of ACL reconstruction were tested: (1) Anatomic Single-Bundle reconstruction (n = 8), the graft was placed at the center of the ACL footprint for the both femoral and tibial sides (tunnel diameter: 8mm); (2) Conventional Single-Bundle reconstruction (n = 8), the graft was placed from the tibial PL footprint to femoral high AM position (tunnel diameter: 8mm) and (3) Anatomic Double-Bundle reconstruction (n = 8). The acceleration in each of three x-y-z directions and the overall magnitude of acceleration was calculated to evaluate dynamic rotational laxity and compared between different ACL reconstructions. RESULTS: The overall magnitude of acceleration was significantly different between ACL intact and deficient knees (p < 0.0001). The acceleration was reduced by the DB ACL reconstruction to the intact level (n.s.), but the two SB ACL reconstruction failed to achieve the intact level of the acceleration (p = 0.0002non-anatomic SB, p < 0.0001 anatomic SB). CONCLUSION: The anatomic DB reconstruction better restores dynamic rotational laxity when compared to the SB ACL reconstructions no matter if the tunnel placement was anatomic. The anatomic DB reconstruction better restores dynamic rotational laxity when compared to both anatomic and non-anatomic SB ACL reconstruction. For this reason anatomic DB ACL reconstruction is recommended for cases where rotational laxity is an issue.

A study of autorotating plant seeds.

A leading edge vortex exists on the upper surface of an autorotating plant seed. The vortex enhances the vertical aerodynamic force acting on the seed and decreases the rate of descent. We analyzed the flight data of rotary seeds and revealed that the lift-drag ratio affects the descent factor more strongly than the vertical force coefficient. This has also been confirmed by falling tests of model rotors, which have various aspect ratios, airfoil shapes and total masses.

Partial anomalous pulmonary venous connection with portosystemic shunt in a cat.

A nine-month-old castrated male domestic shorthair presented for evaluation with a three-month history of hematuria. Portosystemic shunts and calculi within the bladder were suspected, and computed tomography angiography was performed. Computed tomography angiography identified an extrahepatic portosystemic shunt and a partial anomalous pulmonary venous connection, with the lobar vein of the right caudal lobe draining into the caudal vena cava. After anesthesia was administered to the cat, tachypnea and wheezing respiratory sounds were observed, and thoracic radiography revealed the right middle lung lobe atelectasis and an unstructured interstitial pattern in the left cranial lobe. Echocardiography showed left and right atrial enlargement and slight interventricular septal flattening in diastole. Based on these findings, cardiogenic pulmonary edema was suspected, and the cat was treated with furosemide. The clinical symptoms were resolved the next day. Closure of the extrahepatic portosystemic shunt was performed on days 47 and 157. Left atrial enlargement and interventricular septal flattening were attenuated after the procedure. At the time of writing this report (seventeen months after diagnosis), the cat exhibited no clinical signs, but subjective right atrial enlargement remained at approximately the same level. This report represents the first case of a partial anomalous pulmonary venous connection and a portosystemic shunt in a cat.

TB-related technical enquiries received in Japan, 2017-2019.

SETTING: Japan, an intermediate TB burden country. OBJECTIVE: To review TB-related technical enquiries received at the Research Institute of Tuberculosis, Japan, from January 2017 to December 2019. DESIGN: This was a cohort study. RESULTS: A total of 2,197 enquiries were analysed. On average, 61.0 enquiries/month (range: 42-81) were received. The enquiry rates were highest for the Yamanashi (4.65/100,000 population) and Ishikawa (4.55) Prefectures, and lowest in the Yamagata (0.46) and Tochigi (0.56) Prefectures. The main organisations the enquirers belonged to were local governments (n = 1,585, 72.1%) and healthcare facilities (n = 307, 14.0%). The enquirers were medical doctors (n = 391, 17.8%), nurses (n = 1,207, 54.9%), other healthcare professionals (n = 57, 2.6%), the general public (n = 168, 7.6%) and others/unknown (n = 374, 17.0%). The most frequent enquiries were about TB diagnosis and treatment (n = 501, 22.8%), including laboratory diagnosis (n = 88, 4.0%), TB treatment in general (n = 93, 4.2%) and management of comorbidities (n = 86, 3.9%), followed by contact investigations (n = 385, 17.5%) and TB in foreigners (n = 344, 15.7%). CONCLUSION: As the most frequent enquiries were about diagnosis and treatment of TB, the health ministry of Japan should maintain a few specialised TB institutions with TB physicians to provide technical assistance.

LIEU: Le Japon, un pays à charge intermédiaire en matière de TB. OBJECTIF: Examiner les demandes de renseignements techniques liées à la TB reçues au Research Institute of Tuberculosis, au Japon, de janvier 2017 à décembre 2019. METHODE: Il s'agissait d'une étude de cohorte. RÉSULTATS: Au total, 2 197 demandes ont été analysées. En moyenne, 61,0 demandes de renseignements/mois (fourchette : 42­81) ont été reçues. Les taux de demande étaient les plus élevés dans les préfectures de Yamanashi (4,65/100 000 habitants) et d'Ishikawa (4,55), et les plus faibles dans les préfectures de Yamagata (0,46) et de Tochigi (0,56). Les principales organisations auxquelles appartiennent les enquêteurs sont les administrations locales (n = 1 585 ; 72,1%) et les établissements de santé (n = 307; 14,0%). Les enquêteurs étaient des médecins (n = 391 ; 17,8%), des infirmières (n = 1 207 ; 54,9%), d'autres professionnels de la santé (n = 57 ; 2,6%), le grand public (n = 168 ; 7,6%) et autres/inconnus (n = 374 ; 17,0%). Les demandes les plus fréquentes concernaient le diagnostic et le traitement de la TB (n = 501 ; 22,8%), y compris le diagnostic en laboratoire (n = 88 ; 4,0%), le traitement de la TB en général (n = 93 ; 4,2%) et la prise en charge des comorbidités (n = 86 ; 3,9%), suivis par les enquêtes sur les contacts (n = 385 ; 17,5%) et la TB chez les étrangers (n = 344 ; 15,7%). CONCLUSION: Comme les demandes de renseignements les plus fréquentes concernaient le diagnostic et le traitement de la TB, le ministère de la santé du Japon devrait maintenir quelques institutions spécialisées dans la TB avec des médecins spécialistes de la TB pour fournir une assistance technique.

Variation in antagonism of the interferon response to rotavirus NSP1 results in differential infectivity in mouse embryonic fibroblasts.

Rotavirus NSP1 has been shown to function as an E3 ubiquitin ligase that mediates proteasome-dependent degradation of interferon (IFN) regulatory factors (IRF), including IRF3, -5, and -7, and suppresses the cellular type I IFN response. However, the effect of rotavirus NSP1 on viral replication is not well defined. Prior studies used genetic analysis of selected reassortants to link NSP1 with host range restriction in the mouse, suggesting that homologous and heterologous rotaviruses might use their different abilities to antagonize the IFN response as the basis of their host tropisms. Using a mouse embryonic fibroblast (MEF) model, we demonstrate that heterologous bovine (UK and NCDV) and porcine (OSU) rotaviruses fail to effectively degrade cellular IRF3, resulting in IRF3 activation and beta IFN (IFN-beta) secretion. As a consequence of this failure, replication of these viruses is severely restricted in IFN-competent wild-type, but not in IFN-deficient (IFN-alpha/beta/gamma receptor- or STAT1-deficient) MEFs. On the other hand, homologous murine rotaviruses (ETD or EHP) or the heterologous simian rotavirus (rhesus rotavirus [RRV]) efficiently degrade cellular IRF3, diminish IRF3 activation and IFN-beta secretion and are not replication restricted in wild-type MEFs. Genetic reassortant analysis between UK and RRV maps the distinctive phenotypes of IFN antagonism and growth restriction in wild-type MEFs to NSP1. Therefore, there is a direct relationship between the replication efficiencies of different rotavirus strains in MEFs and strain-related variations in NSP1-mediated antagonism of the type I IFN response.

The mandible advancement may alter the coordination between breathing and the non-nutritive swallowing reflex.

The coordination between nasal breathing and non-nutritive swallowing serves as a protective reflex against potentially asphyxiating material, i.e. saliva and secretions, entering the respiratory tract. Although this protective reflex is influenced by positional changes in the head and body, the effect of mandible position on this reflex is not fully understood. We examined the effect of mandible advancement associated with mouth opening on the coordination between nasal breathing and non-nutritive swallowing induced by continuous infusion of distilled water into the pharyngeal cavity. The combination of mandible advancement and mouth opening increased the duration of swallowing apnoea and submental electromyographic burst duration. When the mandible was advanced with the mouth open, the duration of swallowing apnoea increased significantly compared with the centric position (0.79 +/- 0.23 vs. 0.64 +/- 0.12 s, P < 0.05, n = 12), and the duration of submental electromyographic activity increased significantly (2.11 +/- 0.63 vs. 1.46 +/- 0.25 s, P < 0.05, n = 12). Mandible advancement with mouth opening altered the respiratory phase resetting during swallowing and the timing of swallow in relation to respiratory cycle phase. We conclude that mandible re-positioning may strongly influence the coordination between nasal breathing and non-nutritive swallowing by altering respiratory parameters and by inhibiting movement of the tongue-jaw complex.

Effects of aminoguanidine on infertile varicocelized rats: A functional and morphological study.

UNLABELLED: BACKGROUNDS AND THE PURPOSE OF THE STUDY: Inducible NO synthase activity has been frequently reported in varicose veins. Aminoguanidine is known to inhibit iNOS. The aim of this study was to examine the effects of aminoguanidine on varicocelized rats. METHODS: Male Wistar rats were divided into groups A, B, C, D, E, and F (control group). Groups A, B, C, and D rats underwent left varicocele induction with a 20-gauge needle. Group E (sham) rats underwent a similar procedure, but the renal vein was left intact. Ten weeks after varicocele induction, sperm parameters were evaluated in groups D, E, and F. Groups A and B received 50 mg/kg aminoguanidine or placebo, respectively, daily for 10 weeks. After 10 and 20 weeks of varicocele induction, the fertility outcomes of the experimental groups were evaluated. RESULTS: The values of the sperm parameters did not differ significantly between groups B and D, but were significant when compared with groups F and E (P≤0.05). The values of the sperm parameters of groups F and E showed no significant changes (P≤0.05). The changes between group A and groups B and D were significant (P≤0.05). Ten weeks after varicocele induction, rats of groups A, B, and C were still fertile. After 20 weeks, only half of the rats in group A were fertile. CONCLUSIONS: Aminoguanidine improved the sperm parameters and mating outcomes in vari-cocelized rats.

Does aggressive respiratory rehabilitation after primary nuss procedure improve pulmonary function?

OBJECTIVE: Here, we present the efficacy of an aggressive respiratory rehabilitation program that was initiated from early postoperative period, expecting to improve inspiratory volume at an early stage after primary Nuss procedure. METHODS: The study was performed as a nonrandomized controlled study undergoing primary Nuss procedure at our institute from 2016 to 2018. We evaluated 34 patients and assigned them to two groups based on whether or not they received a respiratory rehabilitation. Group A (between June 2016 and March 2018) includes patients with inspiratory training postoperatively, and group B (between April 2018 and July 2018) includes patients without training. At the time of admission, a physiatrist provided each patient with a training instruction. From day five postoperatively, the patients in group A started training for inspiration with an incentive spirometer (Coach 2®PORTEX) four times a day. Patients were instructed to perform the same training at home after discharge. Using this device, we measured pre- and postoperative inspired volumes in each group. Data were analyzed with Wilcoxon-Mann-Whitney tests and a paired Student t-test. A p-value below 0.05 was considered statistically significant. RESULTS: There were no statistically significant differences between the two groups concerning both operative age and the degree of the deformity calculated by Haller index. Preoperative inspiratory volume showed no significant differences. Although there were no statistical differences between two groups in the inspiratory volume at discharge, these two parameters were significantly higher in group A after three months postoperatively (A: 1404 ±â€¯466 ml vs B: 900 ±â€¯314 ml) and the values increased compared to the preoperative stage in group A. CONCLUSIONS: These data indicate the aggressive respiratory rehabilitation is an effective regimen to increase inspiratory volume at an early stage after Nuss procedure. LEVEL OF EVIDENCE: III.

The first case of chronic pulmonary Mycobacterium shigaense infection in an immunocompetent patient.

Mycobacterium shigaense has recently been recognized as an emerging human pathogen, and is well known as a skin pathogen in immunocompromised individuals. In this report we describe the first case of chronic pulmonary infectious disease caused by M. shigaense in an immunocompetent individual.

Isolation and characterization of the plant glsA promoter from Alstroemeria.

The differentiation of a vegetative cell and a generative cell is a critical event during pollen development. The Lilium GlsA is known to localize in pollen and is considered to be involved in development of the generative cell. Here, we cloned a glsA ortholog from Alstroemeria, a commercially important cut flower. The expression of AaglsA (Alstroemeria aurea glsA) transcripts increased gradually after pollen mitosis I (PMI) and reached a significant level when the generative cell started to elongate. Analysis of the promoter of AaglsA suggests that AaglsA expression is controlled by several cis-regulatory elements during pollen development. This is the first investigation of reproductive factors regulating male gametogenesis in Alstroemeria.

Impact of gastro-oesophageal reflux disease symptoms on COPD exacerbation.

BACKGROUND: The association between gastro-oesophageal reflux disease (GORD) and chronic obstructive pulmonary disease (COPD) exacerbation has so far remained unclear. OBJECTIVE: To prospectively establish the clinical significance of GORD symptoms on exacerbation. METHODS: 82 patients with COPD and 40 age matched controls were enrolled in this study. Symptoms were evaluated by a questionnaire using the Frequency Scale for the Symptoms of GORD (FSSG). Patients with COPD were prospectively surveyed for 6 months, and episodes of exacerbation were identified using a diary based on modified Anthonisen's criteria. Exhaled breath condensate (EBC) pH was measured in both groups, and induced sputum was evaluated in patients with COPD. RESULTS: Positive GORD symptoms were reported in 22 (26.8%) patients with COPD and in five (12.5%) controls (p = 0.10). The frequency of exacerbations was significantly associated with the FSSG score (p = 0.03, r = 0.24, 95% CI 0.02 to 0.43). Multiple regression analysis revealed that GORD symptoms were significantly associated with the occurrence of exacerbations (p<0.01; relative risk 6.55, 95% CI 1.86 to 23.11). EBC pH was inversely correlated with FSSG score in both groups (p = 0.01, r = -0.37, 95% CI -0.55 to -0.14 in patients with COPD, and p<0.01, r = -0.45, 95% CI -0.67 to -0.16 in control subjects). CONCLUSIONS: GORD symptoms were identified as an important factor associated with COPD exacerbation.

Clinical application of the Fricke-glucomannan gel dosimeter for high-dose-rate (192)Ir brachytherapy.

This study investigates the efficacy of a new Fricke dosimeter formulation consisting of a standard Fricke gel dosimeter gelled with glucomannan (FrGDG). FrGDG was irradiated using a (192)Ir gamma-ray source with a remote afterloading system based on computed tomography images. (60)Co irradiation was performed for measuring the absorption of FrGDG and water. The distribution maps of T2 values from the irradiated containers were obtained by MR imaging and converted to the absorbed dose to visualize the dose distribution. We found that FrGDG was produced easily and quickly at room temperature. R2 (1/T2) values were reproducible and linearly correlated with the absorbed doses in the range from 0 to 30 Gy for irradiation with (192)Ir (the correlation coefficient was 0.99). The mean deviation between the doses obtained from the MR images of the FrGDG and those calculated by the treatment planning system for doses of 37.5, 40, 50, 62.5 and 75 Gy was 4.9%, 4.8%, 3.5%, 2.3% and 2.4%, respectively. In conclusion, MR imaging of FrGDG can visualize the dose distribution successfully, and thus serves as a useful quality assurance tool for complicated three-dimensional radiotherapy treatments.

Prognostic role of immunosuppressive acidic protein in patients with esophageal cancer.

Immunosuppressive acidic protein (IAP) suppresses several immune responses in vivo and in vitro , and high preoperative IAP levels could predict the impairment of the host's immunity. In this study prognostic significance of preoperative IAP levels was investigated in 68 esophageal cancer patients with curative resection and eight with non-curative resection. The curative group had significantly lower levels than the non-curative group (432 +/- 183 mg/mL vs. 739 +/- 235 mg/mL, P < 0.0001). The IAP levels were associated with T-status (P < 0.0001), lymphatic invasion (P < 0.05), and p-stages (P < 0.0001). When 5-year survival rate of patients with curative resection was compared by setting various cutoff values of IAP between high and low IAP groups, several cutoff points (400-580 mg/mL) were revealed to be significantly associated with survival. Setting cutoff value of IAP to 560 mg/mL resulted in a most significant difference of 5-year survival rate of patients between the high and low IAP groups (13.9% and 61.5%, P < 0.0001). These data indicate that pre-operative IAP level is a useful parameter to predict the prognosis of esophageal cancer patients after curative resection.

Correction osteotomy for malunion of the talar head: a case report.

Talar head fractures are rare injuries. We present a 26-year-old man with malunion of the talar head. The displaced fracture was initially neglected. The patient was treated with osteotomy and bone grafting to improve the congruity and movement of the talonavicular joint. Three months after surgery, he returned to his pre-injury activity level with no disability.

The use of hydroxyapatite blocks for innominate osteotomy: a report of three cases.

We evaluated the use of hydroxyapatite blocks as spacers in pelvic osteotomy. The hydroxyapatite blocks fused with autologous bone tissue within 10 months and were highly biocompatible even after 10 years. They prevent pelvic deformities and are as effective as autogenous bone grafts.

Tuberculosis-related technical enquiries received by a national level institution in Japan, 2014-2016.

Background: Japan had a tuberculosis (TB) notification rate of 13.9 per 100 000 population in 2016. Objectives: To characterise TB-related enquiries received by the Research Institute of Tuberculosis, Tokyo, Japan, between January 2014 and December 2016. Design: A descriptive study of the time, place and other attributes of the enquiries. Results: A total of 1864 enquiries were listed for analysis. On average, 51.8 enquiries (range 30-77) were received per month. The enquiry rates were highest for Yamanashi (5.87/100 000) and Kochi (5.77) Prefectures, and lowest in Miyazaki (0.45) and Saga (0.48) Prefectures. Enquirers belonged mostly to local governments (n = 1212, 65%) and health care facilities (n = 386, 21%), and included medical doctors (n = 412, 22%), nurses (n = 926, 50%) and the general public (n = 150, 8.0%). Most enquiries concerned TB diagnosis and treatment (n = 475, 25%), including diagnosis in general (n = 38, 2.0%), laboratory diagnosis (n = 83, 4.5%), anti-tuberculosis treatment in general (n = 62, 3.3%) and the management of comorbidities or adverse events (n = 60, 3.2%), followed by contact investigations (n = 371, 20%). Conclusions: As most enquiries concerned the diagnosis and treatment of TB, the Ministry of Health of Japan should maintain a number of specialised TB institutions with TB clinicians to provide technical assistance.

Contexte : Le Japon avait un taux de notification de la tuberculose (TB) de 13,9 par 100 000 habitants en 2016.Objectif : Caractériser les demandes liées à la TB reçues par le Research Institute of Tuberculosis, Tokyo, Japon, de janvier 2014 à décembre 2016.Schéma : Une étude descriptive en termes de date, lieu et autres caractéristiques des demandes.Résultats : Un total de 1864 demandes ont été listées pour l'analyse. En moyenne, 51,8 demandes (fourchette 30­77) par mois ont été reçues. Les taux de demande ont été les plus élevés pour les préfectures de Yamanashi (5,87/100 000 habitants) et de Kochi (5,77) et les plus bas dans les préfectures de Miyazaki (0,45) et de Saga (0,48). Les organisations principales auxquelles appartenaient les demandeurs ont été les gouvernements locaux (n = 1212 ; 65%) et les structures de soins de santé (n = 386 ; 21%). Les demandeurs ont été des médecins (n = 412 22%), des infirmiers (n = 926 ; 50%) et le public général (n = 150 ; 8,0%). Les demandes les plus fréquentes ont été liées au diagnostic et au traitement de la TB (n = 475 ; 25%), incluant le diagnostic en général (n = 38 ; 2.0%), le diagnostic de laboratoire (n = 83 ; 4,5%), le traitement de la TB en général (n = 62 ; 3,3%) et la prise en charge des comorbidités ou des effets secondaires (n = 60 ; 3,2%), suivies par la recherche des contacts (n = 371 ; 20%).Conclusion : Comme les demandes les plus fréquentes ont été relatives au diagnostic et au traitement de la TB, le Ministère de la santé du Japon devrait maintenir quelques institutions spécialisées dans la TB avec des cliniciens qui pourraient fournir une assistance technique.

Marco de referencia: En el Japón, la tasa de notificación de tuberculosis (TB) fue 13,9 por 100 000 habitantes en el 2016.Objetivos: Caracterizar las consultas relacionadas con la TB que se recibieron en el Instituto de Investigación en Tuberculosis, Tokyo, Japón, de enero del 2014 a finales de diciembre del 2016.Método: Se llevó a cabo un estudio descriptivo de las consultas con respecto al tiempo, el lugar y otros atributos de las mismas.Resultados: Se registraron 1864 consultas para análisis. En promedio, se recibieron 51,8 consultas por mes (entre 30 y 77). La tasa de consultas más alta correspondió a las prefecturas de Yamanashi (5,87/100 000 habitantes) y Kochi (5,77) y la más baja a las prefecturas de Miyazaki (0,45) y Saga (0,48). Las principales organizaciones de los solicitantes pertenecían a los gobiernos locales (n = 1212; 65%) y a los establecimientos de salud (n = 386; 21%). Los solicitantes fueron médicos (n = 412; 22%), enfermeros (n = 926; 50%) y el público en general (n = 150; 8,0%). Las consultas más frecuentes se relacionaban con el diagnóstico y el tratamiento de la TB (n = 475; 25%), entre otros, el diagnóstico en general (n = 38; 2,0%), el diagnóstico en el laboratorio (n = 83; 4,5%), el tratamiento antituberculoso en general (n = 62; 3,3%) y el manejo de las enfermedades intercurrentes o las reacciones adversas (n = 60; 3,2%), seguidos de la investigación de contactos (n = 371; 20%).Conclusiones: Dado que las consultas más frecuentes se referían al diagnóstico y el tratamiento de la TB, el Ministerio de Salud del Japón debe conservar algunas instituciones especializadas en TB con médicos experimentados que presten asistencia técnica en esta esfera.

Pigmented villonodular synovitis of the elbow in a 6-year-old girl: a case report.

Pigmented villonodular synovitis of the elbow is rare and even rarer in children. We report a case of pigmented villonodular synovitis of the elbow in a 6-year-old girl who underwent total synovectomy after the diagnosis was confirmed by biopsy. The osteochondral defect at the olecranon was filled with calcium phosphate bone paste. Two years after surgery, neither recurrence nor joint degeneration was found.

Controlling the lectin recognition of glycopolymers via distance arrangement of sugar blocks.

The arrangement of sugars in glycopolymers contributes to their recognition. The molecular recognition of proteins was controlled by the living radical polymerization of glycopolymers. The glycopolymers were prepared by the copolymerization of propargyl methacrylate (Pr-MA) and triethyleneglycol methacrylate (TEG-MA) via living radical polymerization with a reversible addition-fragmentation glycopolymer chain transfer (RAFT) reagent and by subsequent sugar conjugation by click chemistry. The block copolymers were prepared by the polymerization of Pr-MA and TEG-MA. The molecular recognition of glycopolymers was analyzed using the fluorescence quenching of lectin and found to be dependent on the glycopolymer structures. Two-site binding of glycopolymers to concanavalin A (ConA) was attained by both the glycopolymer with a 105-mer and the tri-block glycopolymer with a 103-mer. Glycopolymers with either a 27- or 54-mer showed much weaker interaction because of one-site binding. The molecular recognition of the glycopolymer was controlled by the arrangement and size of the sugar cluster and not by the sugar density.

Transcriptional activation of the zinc finger transcription factor BTEB2 gene by Egr-1 through mitogen-activated protein kinase pathways in vascular smooth muscle cells.

We have recently demonstrated that a developmentally regulated zinc finger protein, basic transcription regulatory element binding protein 2 (BTEB2), is induced in neointimal smooth muscle in response to vascular injury. In this study, we investigated the molecular mechanisms regulating BTEB2 expression in vascular smooth muscle cells (SMCs) in vitro. BTEB2 mRNA expression is rapidly and persistently induced in SMCs by phorbol 12-myristate 13-acetate (PMA) and basic fibroblast growth factor. We have isolated and characterized the promoter region of the human BTEB2 gene to determine the regulatory network controlling expression of this gene in vascular SMCs. Functional studies on the BTEB2 promoter coupled to a luciferase reporter gene demonstrated activation of the promoter by PMA and basic fibroblast growth factor. Both characterization of DNA-protein complexes in vitro and site-specific mutation analysis of the BTEB2 promoter have defined a 9-bp sequence, 5'-CGCCCGCGC-3', located at -25, as the Egr-1 binding site mediating an induction of the BTEB2 promoter activity by PMA. In addition, we show that this site mediates inducible expression through the mitogen-activated protein kinase pathways. These results indicate that BTEB2 is a target of the early-response gene Egr-1, and mitogen-activated protein kinase pathways directly or indirectly activate BTEB2 expression. Given a rapid induction of Egr-1 on stimulation with growth factors or injury, these findings may represent at least one of the molecular mechanisms underlying phenotypic modulation of smooth muscles after vascular injury.