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Biomedical subjects

Jun Kobayashi

Publications and source records attributed to Jun Kobayashi.

At least 19 recordsLinked to original sources

Beyond deworming: the promotion of school-health-based interventions by Japan.

Deworming bestows a variety of health and socioeconomic benefits and has been embraced by developing countries. To extend the beneficial impact of deworming, the Asian Centre of International Parasite Control (ACIPAC) project has carried out activities to link deworming with health-promoting school programs in the Greater Mekong Subregion (Cambodia, Laos, Myanmar, Thailand and Vietnam). ACIPAC has also conducted an integrated school-health-based program, including deworming and malaria education, under the umbrella of the health-promoting schools initiative. Implementing "beyond-deworming" efforts is now a practical challenge in the subregion.

Animals↗

Direct-type catalytic three-component mannich reactions leading to an efficient synthesis of alpha,beta-diamino acid derivatives.

[reaction: see text] The first example of the Lewis acid-catalyzed three-component direct-type Mannich reaction of simple aromatic and enolizable aliphatic aldehydes, secondary amines, and glycine derivatives is described. The procedure is highly atom economical and can be performed in a simple one-pot operation under mild conditions to afford a wide variety of synthetically important anti-alpha,beta-diamino ester derivatives in high yields with high diastereoselectivities.

Aldehydes↗

Keys to success for a school-based malaria control program in primary schools in Thailand.

School-based malaria control has been recognized as a new approach for the control of this disease in the Greater Mekong Subregion since 2000. We evaluated a school-based malaria control program near the western border of Thailand using a before-after intervention study. The major intervention activities included teacher training with specialized malaria teaching materials and participatory learning methods. The target population was 17 school principals, 111 teachers and 852 schoolchildren of grade 3, 4, and 5 in 17 schools. After the intervention, the teachers taught about malaria more actively than before. The teachers who could design a lesson plan on malaria increased from 30.7% to 47.7% (p=0.015) and the teachers who had taught about malaria increased from 71.9% to 84.3% (p=0.035). As a result of the program, the schoolchildren changed their behavior positively towards malaria prevention with significant difference in 6 of 7 questions. For example, the schoolchildren 'who always took care of mosquito bites' increased from 42.7% to 62.1% (p<0.001) and the schoolchildren 'who always reported their parents or teachers when they had fever' increased from 36.0% to 56.0% (p<0.001). In conclusion, the keys to a successful intervention lie in good teaching materials and a participatory approach utilizing the well-established Thailand's school health system. Beyond Thailand, school-based malaria control could be applied to other Greater Mekong Subregion countries with careful analysis of school health context in each country.

Adult↗

Thermal modulated interaction of aqueous steroids using polymer-grafted capillaries.

Poly(N-isopropylacrylamide) (PIPAAm) of controlled molecular weight was densely grafted onto glass capillary lumenal surfaces using surface-initiated atom transfer radical polymerization (ATRP). Temperature-dependent changes of these thermoresponsive brush surfaces with hydrophobic steroids were investigated by exploiting thermoresponsive aqueous wettability changes of the polymer-modified surfaces in microfluidic systems. IPAAm was polymerized on ATRP initiator-immobilized glass surfaces using CuCl/CuCl(2)/tris(dimethylaminoethyl)amine (Me(6)TREN) as an ATRP catalyst in water at 25 degrees C. PIPAAm graft layer thickness and its homogeneity on glass surfaces are controlled by changing ATRP reaction time. Aqueous wettability changes of PIPAAm-grafted surfaces responses drastically changed to both grafted polymer layer thickness and temperature, especially at lower temperatures. Temperature-responsive surface properties of these PIPAAm brushes within capillary inner wall surfaces were then investigated using capillary chromatography. Effective interaction of hydrophobic steroids with dehydrated, hydrophobized PIPAAm-grafted capillary surfaces was observed above 30 degrees C without any column packing materials. Steroid elution behavior from PIPAAm-grafted capillaries contrasted sharply with that from PIPAAm hydrogel-grafted porous monolithic silica capillaries prepared by electron beam (EB) irradiation wherein significant peak broadening was observed at high-temperature regardless of sample hydrophobicity factors (log P values), indicating multistep separation modes in coated monolithic silica capillaries. In conclusion, thermoresponsive polymer-grafted capillary inner wall surfaces prepared by ATRP exhibit useful temperature-dependent surface property alterations effective to regulate interactions with biomolecules without requirements for separation bed packing materials within the capillary lumen.

Journal Article↗

Development of a human mammary epithelial cell culture model for evaluation of drug transfer into milk.

In the present study, a human mammary epithelial cell (HMEC) culture model was developed to evaluate the potential involvement of carrier-mediated transport systems in drug transfer into milk. Trypsin-resistant HMECs were seeded on Matrigel-coated filters to develop monolayers of functionally differentiated HMEC. Expression of the specific function of HMEC monolayers was dependent of the number of trypsin treatments. Among the monolayers with different numbers of treatment (treated 1 to 3 times), the monolayer treated 3 times (3-t-HMEC monolayer) showed the highest maximal transepithelial resistance and expression of beta-casein mRNA as an index of differentiation. Transport of tetraethylammonium (TEA) across the 3-t-HMEC monolayer in the basolateral-to-apical direction was significantly higher than that in the apical-to-basolateral direction (p < 0.05), whereas such directionality was not observed for p-amino-hippurate, suggesting the existence of organic cation transporters, but not organic anion transporters. In fact, expression of mRNAs of human organic cation transporter (OCT) 1 and 3 were detected in the 3-t-HMEC monolayer. These results indicate that the 3-t-HMEC monolayer is potentially useful for the evaluation of carrier-mediated secretion of drugs including organic cations into human milk.

Biological Transport↗

Maskless liquid-crystal-display projection photolithography for improved design flexibility of cellular micropatterns.

We previously developed an all-in-one photopolymerization device by modifying a commercially available liquid crystal display projector (LCDP) for the preparation of micropatterned surfaces and microfluidic channels without the need for expensive photomasks. In the present study, we demonstrate a simple and reliable method for rapid prototyping of cell micropatterning with high resolution using the modified LCDP device. Fabrication of complicated and flexible patterns was achieved using this device with positive-type photoresist in a two-step process. First, micropatterns on the silanized coverslips were fabricated from positive photoresist. Second, acrylamide monomer solution containing polymerization initiator was dropped onto the micropatterned positive photoresist and copolymerized on the silanized coverslips in situ by thermally initiated radical polymerization. After the reaction, the remnant micropatterned photoresist is easily dissolved, resulting in a polyacrylamide-silane micropattern on the coverslip. The resultant polyacrylamide layer is highly hydrophilic and repels both protein adsorption and cell adhesion. Cells seeded on the micropatterned surfaces therefore attach and spread only on unpolymerized silanized glass surfaces, conforming to the pattern design. This technique is therefore useful for inexpensive, rapid prototyping of surface micropatterns using polymer materials.

Acrylic Resins↗

[A case of endobronchial lesion due to infection with Mycobacterium intracellulare].

A 53-year-old man was hospitalized in April 2001 because of left cervical lymphadenopathy and a mass shadow in the left lingular segment. Bronchoscopy revealed an elevated lesion in the left main bronchus, but a biopsy showed no specific findings. A left cervical lymph node biopsy revealed lymphoid hyperplasia only and no malignancy. After the patient was discharged, bronchial irrigation solution from the left lingular segment was found to be positive for Mycobacterium intracellulare. In July 2001 the shadow in the left lingular segment had worsened, and bronchoscopy was performed again. This revealed ulceration in the left main bronchus and edematous narrowing of the bronchial lumen at the opening of the lingular segment. A granulated lesion accompained by severe inflammation was seen in a biopsied specimen taken from the same site. Bronchial lesion induced by an acid-fast-stain positive nontuberculosis mycobacteria was noted. Treatment with rifampicin (RFP), clarithromycin (CAM), ethambutol (EB), and streptomycin (SM) was started, but a rash most likely caused by RFP developed, and RFP was replaced by ciprofloxacin (CPFX). The treatment was continued and symptoms improved. Since non-tuberculous mycobacteriosis accompanied with bronchial lesions is rare, a case report was made.

Bronchi↗

Adhesiveness of beta5 integrin variant lacking FNK767-769 is similar to that of the prototype containing FNKFNK764-769.

Little is known about the functions of two different beta5 integrins: repeated-FNK (FNKFNK764-769) and single-FNK (FNK764-766) amino acid sequences in the cytoplasmic domain. We examined whether they occurred as germ line mutations or somatic mutations associated with neoplastic transformation, and whether there were functional alterations. Out of six cultured cell lines, only KATO-III cells had the single-FNK beta5 sequence. The single-FNK beta5 was found in 9 out of 79 patients with colon carcinoma, but no somatic mutations were detected in cancerous tissues. CHO cells were transformed with expression vectors containing single-FNK or repeated-FNK beta5 cDNA, which were derived from KATO-III cells. CHO cells transfected with single-FNK and repeated-FNK showed similar adhesiveness to, and proliferative activity on, vitronectin substrates.

Amino Acid Sequence↗

Usefulness of selective contrast echocardiography and selective scintigraphy for the evaluation of pulmonary arteriovenous fistula in a patient with systemic arterial supply to a normal lung.

To determine a surgical procedure for the correction of a systemic arterial supply to a normal lung, it is important to evaluate whether the patient has a pulmonary arteriovenous fistula. In this article, the authors report for the first time a patient in which selective contrast echocardiography and selective perfusion scintigraphy from an abnormal artery clearly demonstrated and quantified the pulmonary arteriovenous fistula. The authors believe that these methods are useful in determining the appropriate operative procedure for this condition.

Aorta, Thoracic↗

[A case of non-curatively resected scirrhous gastric cancer successfully treated over 2 years with weekly administration of paclitaxel].

We report a patient with far-advanced gastric cancer treated by weekly administration of paclitaxel (TXL) over 2 years. The patient was a 66-year-old female with peritoneal metastasis and remarkable lymph node metastasis of scirrhous gastric cancer. She underwent a non-curative resection with total gastrectomy and splenectomy in May 2002. Postoperative chemotherapy with TS-1 (80 mg/body) was performed. Due to grade 4 neutropenia and grade 2 anorexia, this treatment could not be continued. Three months after surgery, the tumor marker (CA19-9) had elevated to an abnormal level. Alternatively, TXL was administered at a weekly dose of 70 mg/m2 for 3 weeks followed by 6 weeks rest from September 2002. The tumor marker (CA19-9) gradually decreased to the normal level. Because of the long rest interval, 10 courses of treatment could be continued, and the patient has been alive over 2 years with the cancer controlled. There have been few effective chemotherapies for gastric cancer with peritoneal metastasis. Weekly paclitaxel therapy is considered to be effective for the treatment of advanced scirrhous gastric cancer with peritoneal metastasis.

Adenocarcinoma, Scirrhous↗

A molecular epidemiologic study of point mutations for pyrimethamine-sulfadoxine resistance of Plasmodium falciparum isolates from Lao PDR.

To understand the current condition of pyrimethamine-sulfadoxine (PS) resistant falciparum malaria in Lao PDR, the frequency of point mutations in dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) genes of Plasmodium falciparum were examined in 50 blood samples collected from the patients with P. falciparum infection in Southern Lao PDR. Point mutations in 5 codons of the DHFR gene, which is known to be related to pyrimethamine resistance, were detected in 15 out of the 50 samples (30%). Among the 15 samples, 10 samples showed a double mutation of codons 59 and 108 (Cys59Arg with Ser108Asn). In the remaining 5 samples, an additional mutation was observed in codon 51 (Asn51 lle), providing a triple mutation of codons 51, 59 and 108. On the other hand, point mutations in the 4 codons of DHPS gene related to sulfadoxine resistance were observed only in 2 samples (4.0%), namely in codon 437 (Ala437Gly). Only one sample showed mutations in both DHFR and DHPS genes. From the results, it should be considered that the frequency of PS resistant malaria is still low in Lao PDR. Continuous monitoring for the PS resistant malaria, however, is necessary because of the increasing use of PS in this country.

Animals↗

[A case of pulmonary epithelioid hemangioendothelioma detected on medical checkup].

A 51-year-old woman was admitted to our hospital because of bilateral multiple nodular shadows detected on a medical checkup chest X-ray film. Video-assisted thoracoscopic biopsy and hematoxylin eosin staining showed protrusion of the polypoid tumor tissue into the alveolar lumina, and the centers of nodules were occupied by hyalinized matrices. Immunohistochemical stain demonstrated that tumor cells were positive for factor VIII-related antigen, CD-34, and vimentin. The tumor was therefore diagnosed as pulmonary epithelioid hemangioendothelioma (PEH). PEH usually grows slowly. Standard therapy for PEH has not yet been established. We have followed the patient for 2 years without any treatment, but no symptoms have appeared.

Biopsy↗

Pyrimethamine-sulfadoxine treatment of uncomplicated Plasmodium falciparum malaria in Lao PDR.

A 28-day in vivo treatment trial to evaluate the efficacy of pyrimethamine/sulfadoxine (Fansidar, PS) was conducted in 21 Lao patients with uncomplicated Plasmodium falciparum malaria. Sixteen patients (76%) were completely cured with PS without any reappearance of asexual stage parasitemia during the follow-up examination. On the other hand, 5 patients (24%) failed to respond to this trial medication, resulting in recrudescence of asexual stage P. falciparum malaria. PS resistance resulted in higher prevalence of post-treatment gametocytemia, 25% gametocyte carriers among PS sensitive cases versus 75% of the resistant cases. These findings suggest that although the level of PS resistance is still valid for treatment of malaria in the study area of Lao PDR, post-treatment induction of gametocytemia among resistant cases may result an increase in transmission rate of PS resistant falciparum malaria.

Adolescent↗

Synthesis of a new chiral source, (1R,2S)-1-Phenylphospholane-2-carboxylic acid, via a key intermediate alpha-phenylphospholanyllithium borane complex: configurational stability and X-ray crystal structure of an alpha-monophosphinoalkyllithium borane complex.

A synthetic route to enantiomerically pure (1R,2S)-1-phenylphospholane-2-carboxylic acid (1), which is a phosphorus analogue of proline, has been established. A key step is the deprotonation-carboxylation of the 1-phenylphospholane borane complex 3 by using sBuLi/1,2-dipiperidinoethane (DPE). Configurational stability of the key intermediate, the amine-coordinated alpha-phosphinoalkyllithium borane complex 4, was investigated by employing lithiodestannylation-carboxylation of both diastereomers of the 1-phenyl-2-trimethylstannylphospholane borane complex 7 in the presence of several kinds of amines, and as a result, 4 was found to be configurationally labile even at -100 degrees C. The key intermediate, the DPE-coordinated trans-1-phenyl-2-phospholanyllithium borane complex 9, was isolated, and the structure was identified by X-ray crystal structure analysis. This is the first X-ray crystal structure determined for an alpha-monophosphinoalkyllithium borane complex. Remarkably, the alkyllithium complex is monomeric and tricoordinate at the lithium center with a slightly pyramidalized environment, and the existence of a Li--C bond (2.170 A) has been confirmed. Moreover, (1)H-(7)Li HOESY and (6)Li NMR analyses suggested the structure of 9 in solution as well as the existence of an equilibrium between 9, its cis isomer, and the ion pair 8 at room temperature, which was extremely biased towards 9 at -100 degrees C. Finally, 1 was used as a chiral ligand in a palladium-catalyzed allylic substitution, and the desired product was obtained in high yield with good enantioselectivity.

Boranes↗

Catalytic enantio- and diastereoselective aldol reactions of glycine-derived silicon enolate with aldehydes: an efficient approach to the asymmetric synthesis of anti-beta-hydroxy-alpha-amino acid derivatives.

We have developed an efficient method for the asymmetric synthesis of anti-beta-hydroxy-alpha-amino acid derivatives based on highly enantio- and diastereoselective aldol reactions of the silicon enolate derived from N-trifluoroacetylglycinate with aldehydes using a chiral zirconium catalyst. The resulting N-trifluoroacetyl group is easily cleaved under either acidic or basic conditions and can be used directly as a protecting group for further transformations.

Aldehydes↗

Micropatterned surfaces prepared using a liquid crystal projector-modified photopolymerization device and microfluidics.

A commercial liquid crystal device projector was modified for photopolymerization using its on-board intense light source and a precision optical control circuit. This device projects reduced images generated by a typical personal computer onto the stage where photopolymerization on a surface occurs. This all-in-one device does not require expensive photomasks and external light sources. However, light scattering and diffraction through glass substrates resulted in undesired reactions in areas corresponding to masked (black) domains in mask patterns, limiting pattern resolution. To overcome this shortcoming, two-step surface patterning was developed. First, three-dimensional microstructures of crosslinked silicone elastomer were fabricated with this device and adhered onto silanized glass substrate surfaces, forming microchannels in patterns on the glass support. Then, acrylamide monomer solution containing photoreactive initiator was flowed into these micromold channels and reacted in situ. The resultant polyacrylamide layer was highly hydrophilic and repelled protein adsorption. Cell seeding on these patterns in serum-supplemented culture medium produced cells selectively adhered to different patterns: cells attached and spread only on unpolymerized silanized glass surfaces, not on the photopolymerized acrylamide surfaces. This technique should prove useful for inexpensive, rapid prototyping of surface micropatterns from polymer materials.

Acrylic Resins↗

The effectiveness of impregnated bed net in malaria control in Laos.

Impregnated bed net (IBN) were used in 366 villages in the central and southern three provinces of Lao PDR from 1999 to 2000. It was confirmed that 81.0% of 40000 bed nets, which were donated by Japanese Grant Aid, were delivered within 2 years. The strengthening of information network systems in anti-malaria and strong relationship between community and local authorities ensured the success of operation in a short period. The number of patients and the slide positive rate of malaria decreased markedly in public health facilities in three provinces after the use of IBN. An entomological survey was conducted in Boualapha district, where malaria is endemic, to investigate the IBN efficacy on malaria vector. The density and parous rate of Anopeles dirus, which is the main malaria vector in the area, were markedly decreased in the village where IBN was used. This mosquito's behavior, which was baiting mainly humans during the time when the inhabitants sleep in the IBN, was considered to be advantageous in preventing malaria infection using by IBN. The area of distribution of A. dirus is similar to the high endemic area of malaria in Lao PDR. Thus, it is expected that the expansion of the IBN program in the southern provinces will lead to successful malaria control in subsequent years.

Animals↗

Cell micropatterning using photopolymerization with a liquid crystal device commercial projector.

Photopolymerization has been widely used for surface micropatterning. The technique often requires photomasks and light sources with appropriate energies or filters. For rapid prototyping of surface photo-micropatterning, we have developed a novel device by modifying a commercially available liquid crystal device projector. In place of the image expansion unit of the projector, we attached an image reduction unit, an adjustable stage, and an optical monitoring unit. The device projected computer-generated images onto surfaces and subjected these patterns to photopolymerization. Micropatterned images can be easily prepared with various software run on personal computers. With the developed photopolymerization device, micropatterning of poly(ethylene glycol) (PEG) was achieved with PEG-diacrylate and a visible light photopolymerization initiator, camphorquinone. Selective cell adhesion control was also achieved on the micropatterned surfaces.

Animals↗