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Chiral, racemic esters, ethyl (±)-tetrahydrofuran-2-carboxylate 4c, methyl (±)-α-phenylpropionate 9b, methyl (±)-5,5-dimethyl-1,3-thiazolidine-4-carboxylate 12a, 2-methoxyethyl (±)-1-(4-tert-butylphenyl)-2-oxopyrrolidine-4-carboxylate 15a, (±)-1-benzyloxy-3-chloropropan-2-yl hydrogen succinate 18c, and (±)-3-butyryloxyquinuclidinium butyrate [(±)-20b·n-PrCO2H], are resolved kinetically by enantioselective hydrolysis catalyzed by an Aspergillus melleus protease [E = 60; 93.9% ee and 35% yield for (R)-tetrahydrofuran-2-carboxylic acid 4a], a Klebsiella oxytoca hydrolase [E > 200; 99.5% ee and 36% yield for (S)-α-phenylpropionic acid 9a], a K. oxytoca hydrolase [E = 145; 97.7% ee and 34% yield for (R)-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid 12b], a Bacillus brevis protease [E = 77; 99% ee and 45% yield for (S)-15a], a Serratia marcescence esterase [E = 49; 99% ee and 43% yield for (S)-18c], and an A. melleus protease [E = 96; 96% ee and 42% yield for (R)-20b], respectively. Each enzymatic process is discussed with focus on the following tactical issues:  (1) identification of a hydrolase with high enantioselectivity, (2) substrate concentrations not less than 1 M that allow for industrially viable volume efficiency (space−time yield), (3) product separation by partition between organic and aqueous phases, and (4) alleviation of a hydrolysate inhibiting the enzymatic activity.

(S)-Ibuprofen 2, (S)-ketoprofen 3, and (S)-naproxen 4 are all obtained by optical resolution of the respective racemates with (S)-3-methyl-2-phenylbutylamine (PBA) 1:  (S)-2, 98.7% ee, 39.8% yield; (S)-3, 99.4% ee, 36.7% yield; (S)-4, 99.2% ee, 35.1% yield. (S)-PBA 1 is also useful in resolving other racemic carboxylic acids of pharmaceutical importance; (R)-2-hydroxy-4-phenylbutanoic acid (HPBA) 5, a key intermediate for ACE inhibitors such as benazapril 7, and (S)-2-benzylsuccinic acid (BSA) 6, a key intermediate for hypoglycemic KAD-1229 8, are obtained in 99% ee and 34.4% yield, and in 99% ee and 32.2% yield, respectively.

Abstract. Background: Although hepatocyte growth factor (HGF) is also known as scatter factor, it induces epithelial morphogenesis in cultured bovine retinal pigment epithelial (RPE) cells. To elucidate the mechanism of epithelial morphogenesis, we investigated the influence of HGF on occludin, a major component of tight junctions. Methods: RPE cells were plated on collagen type 1-coated chamber slides or dishes, 20 ng/ml HGF was added and the cells were incubated for 1 week. Cells were harvested at several time-points, and occludin expression was examined by immunohistochemistry. Detergent extraction protocols to identify the intensity of occludin linkage to the cytoskeleton were also used. Occludin expression was determined semiquantitatively by Western blotting. Results: Fluorescence microscopy revealed that HGF treatment increased the levels of insoluble occludin at the cell borders after detergent extraction. These level of insoluble occludin and the associated epithelial morphology were maintained for more than 3 weeks after withdrawal of HGF, whereas cells not treated with HGF had a fibroblastic appearance. Western blotting also showed that insoluble occludin was more abundant in HGF-treated cells. Furthermore, immunoreactive bands of insoluble occludin were somewhat larger than those of soluble occludin, suggesting that insoluble occludin may be modified in comparison to soluble occludin. Conclusion: Our results suggest that HGF promotes linkage of occludin to the cytoskeleton. HGF may become a therapeutic candidate in physiological recovery of RPE cells and in preparation of RPE monolayers for transplantation.

Abstract:  The expression of the Arabidopsis heat shock protein (HSP) 18.2 promoter-β-d-glucuronidase (GUS) chimera gene was investigated in transgenic Nicotiana plumbaginifolia plants during the recovery phase at normal temperatures (20–22  °C) after a heat shock (HS) treatment. GUS activity increased during the recovery phase after HS at 42  °C for 2 h, and maximal GUS activity was observed after 12 h at normal temperatures, at levels 50–100 times higher than the activity immediately after HS. After HS at 44  °C, little GUS activity was observed during the first 20–24 h at normal temperatures, but the activity increased gradually thereafter, to reach a maximum at 40–50 h. After HS at 45  °C, no GUS activity was observed throughout the experimental period. RT-PCR analysis showed that GUS mRNA remained for 10 h after a 2-h HS at 42  °C and for 40 h after a 2-h HS at 44  °C. These findings demonstrate that brief HS treatment, especially at a sublethal temperature, induces a long-term accumulation of HSP-GUS mRNA during the recovery phase.

Aims/hypothesis. To determine whether the clinical heterogeneity observed in the development of Type I (insulin-dependent) diabetes mellitus correlates with immunohistochemical differences observed at diagnosis. Methods. Patients (n= 17) with recent-onset diabetes clinically considered to be insulin dependent (Type I), underwent pancreatic biopsy for immunohistological analysis. These patients were divided into two groups based on the presence or absence of islet immunological abnormalities (insulitis or hyperexpression of MHC class I antigens or both). The patients were also HLA typed and tested for islet cell antibodies and antibodies to glutamic acid decarboxylase (GAD-Ab). All patients were followed monthly for 2 years and their fasting plasma glucose, haemoglobin A1Cand daily insulin doses were recorded. The clinical course of patients with islet immunological abnormalities was compared with that of patients without those abnormalities. Results. Patients with and without islet immunological abnormalities did not differ with regard to HLA type or islet cell antibodies. Antibodies to glutamic acid decarboxylase correlated with the presence of insulitis and MHC class I hyperexpression. These local immunological abnormalities were also associated with higher haemoglobin A1Cvalues (p< 0.05) and a trend towards greater insulin requirements. Further, patients with the islet abnormalities had higher fasting plasma glucose concentrations 2 years after the biopsy than at the time of the biopsy (p< 0.05). Conclusion/interpretation. The heterogeneous clinical course observed following diagnosis in patients with Type I diabetes correlates with islet immunological abnormalities. Insulitis and hyperexpression of MHC class I correlate with deteriorating glycaemic control. [Diabetologia (1999) 42: 574–578]Aims/hypothesis. To determine whether the clinical heterogeneity observed in the development of Type I (insulin-dependent) diabetes mellitus correlates with immunohistochemical differences observed at diagnosis. Methods. Patients (n= 17) with recent-onset diabetes clinically considered to be insulin dependent (Type I), underwent pancreatic biopsy for immunohistological analysis. These patients were divided into two groups based on the presence or absence of islet immunological abnormalities (insulitis or hyperexpression of MHC class I antigens or both). The patients were also HLA typed and tested for islet cell antibodies and antibodies to glutamic acid decarboxylase (GAD-Ab). All patients were followed monthly for 2 years and their fasting plasma glucose, haemoglobin A1Cand daily insulin doses were recorded. The clinical course of patients with islet immunological abnormalities was compared with that of patients without those abnormalities. Results. Patients with and without islet immunological abnormalities did not differ with regard to HLA type or islet cell antibodies. Antibodies to glutamic acid decarboxylase correlated with the presence of insulitis and MHC class I hyperexpression. These local immunological abnormalities were also associated with higher haemoglobin A1Cvalues (p< 0.05) and a trend towards greater insulin requirements. Further, patients with the islet abnormalities had higher fasting plasma glucose concentrations 2 years after the biopsy than at the time of the biopsy (p< 0.05). Conclusion/interpretation. The heterogeneous clinical course observed following diagnosis in patients with Type I diabetes correlates with islet immunological abnormalities. Insulitis and hyperexpression of MHC class I correlate with deteriorating glycaemic control. [Diabetologia (1999) 42: 574–578]

Aims/hypothesis. Type I (insulin-dependent) diabetes results mainly from T-cell-mediated autoimmune destruction of pancreatic beta cells. Cytotoxic T lymphocytes destroy target cells via a perforin-based or Fas-based mechanism. Our previous study indicated that the Fas-Fas ligand (FasL) pathway is required for the development of autoimmune diabetes in the NOD mouse. We now investigated whether or not the Fas-FasL system is involved in the beta-cell destruction in human Type I diabetes. Methods. We immunohistochemically analysed pancreas biopsy specimens of 13 recent-onset patients. Results. Pancreatic islets were identified but showed various degrees of reduction in beta-cell volume in all patients. Out of 13 patients 6 had insulitis. In these 6 patients Fas was expressed in both the islets and infiltrating cells but not in either cell type in the 7 other patients without insulitis. Double immunostaining showed that Fas was positive in 92.2 to 97.7 % of beta cells but only in 17.6 to 46.7 % of alpha cells in Fas-positive, insulin-remaining islets. We found FasL was expressed exclusively in islet-infiltrating cells in patients with insulitis. Double immunostaining revealed that the most prevalent phenotype of FasL-positive cells was CD8, which was followed by macrophages and CD4. Conclusion/interpretation. The interaction between Fas on beta cells and FasL on infiltrating cells might trigger selective apoptotic beta-cell death in inflamed islets, leading to immune-mediated Type I diabetes. [Diabetologia (1999) 42: 1332–1340]Aims/hypothesis. Type I (insulin-dependent) diabetes results mainly from T-cell-mediated autoimmune destruction of pancreatic beta cells. Cytotoxic T lymphocytes destroy target cells via a perforin-based or Fas-based mechanism. Our previous study indicated that the Fas-Fas ligand (FasL) pathway is required for the development of autoimmune diabetes in the NOD mouse. We now investigated whether or not the Fas-FasL system is involved in the beta-cell destruction in human Type I diabetes. Methods. We immunohistochemically analysed pancreas biopsy specimens of 13 recent-onset patients. Results. Pancreatic islets were identified but showed various degrees of reduction in beta-cell volume in all patients. Out of 13 patients 6 had insulitis. In these 6 patients Fas was expressed in both the islets and infiltrating cells but not in either cell type in the 7 other patients without insulitis. Double immunostaining showed that Fas was positive in 92.2 to 97.7 % of beta cells but only in 17.6 to 46.7 % of alpha cells in Fas-positive, insulin-remaining islets. We found FasL was expressed exclusively in islet-infiltrating cells in patients with insulitis. Double immunostaining revealed that the most prevalent phenotype of FasL-positive cells was CD8, which was followed by macrophages and CD4. Conclusion/interpretation. The interaction between Fas on beta cells and FasL on infiltrating cells might trigger selective apoptotic beta-cell death in inflamed islets, leading to immune-mediated Type I diabetes. [Diabetologia (1999) 42: 1332–1340]

Abstract:  The expression of the Arabidopsis heat-shock protein (HSP) 18.2 promoter β-d-glucuronidase (GUS) chimera gene was studied in various organs of the transgenic Nicotiana plumbaginifolia during the recovery phase at normal temperatures (20–22  C) following heat-shock (HS) treatment. The optimum HS temperature for GUS activity in the anthers, petals and capsules was 42  C, but in immature seeds and the placentas of capsules it was 36  C and 39  C, respectively. No apparent GUS activity was observed in any organs except for dry seeds after HS at 45  C, although the activity in dry seeds was apparent even after HS at 48  C. After HS at 42  C, GUS activity in the flower tissues was the highest before anthesis and declined thereafter.

Akabane disease, an infectious disorder causing congenital abnormalities in calves, was studied in naturally affected calves between 1972 and 1974 in Japan. The animals included one three-month fetus from which a strain of Akabane virus (OBE-1) was isolated, and a total of 177 stillborn or premature fetuses and deformed or infirm newborn calves that died within a few days of birth.The three-month fetus had nonpurulent encephalomyelitis in the undifferentiated central nervous system, characterized by necrosis of the nerve tissue and endothelial proliferation in the encephalitic process; and polymyositis in the myotubule phase with parenchymal degeneration and cellular infiltrates in the skeletal muscle.The full-term fetuses and newborn calves had nonpurulent encephalomyelitis in the early stage of the epizootic. In the middle to late stages, a dysplastic muscular change which we call runt-muscle disease was seen simultaneously with a decrease in number of ventral horn neurons in the spinal cord and arthrogryposis in the legs. Cystic cavities and thick vascular walls sometimes were seen in the central nervous system in these stages. Hydranencephaly was prominent in the late stage.

Abstract—Fatigue tests were performed on thin‐walled tubular specimens of S45C steel under tension‐compression, pure torsion, in‐phase and out‐of‐phase axial‐torsional loadings. The relationship between cracking behaviour and stress components on the crack plane was investigated. Measurement of microcrack density showed that microcracking was governed predominantly by the shear stress amplitude acting on the crack plane for all loading conditions. The failure crack was formed by coalescence of many cracks initiated near the maximum shear planes. The cracks grew turning their orientation to the direction perpendicular to the maximum normal stress. The transition of crack orientation occurred at relatively longer crack lengths at a higher stress ratio. The crack growth behaviour for all loading modes can be correlated using an equivalent strain intensity parameter based on shear and normal strains on the crack plane.

The choroidal vessels are three dimensionally distributed and very complex in their patterns. They often appear to be overlaid in indocyanine green (ICG) angiograms so it is harder to analyze ICG angiography than fluorescein angiography. When an earlier frame is subtracted from a later frame in a sequence of angiograms, the fluorescence which has increased during the time between the two frames can theoretically be demonstrated.We applied computer-assisted image subtraction methods in selected clinical cases of directly acquired digital ICG angiography to demonstrate how this method works. We used software already installed in an IMAGEnet computer system (Topcon) for image subtraction. We applied the subtraction technique in 18 cases with various diseases. When two images with a time difference of several seconds were subtracted, filling of the choriocapillaris, the neovascularization or the pathological vessels could be observed. When the images had a time difference of several minutes, intrachoroidal dye leakage could be seen more clearly. This method is very helpful for analyzing pathological changes in ICG angiography in clinical cases, when two images are selected appropriately.

Image processing with direct acquisition digital fundus fluorescein angiography using the OIS DFC-512 and Topcon IMAGEnet were assessed. Fundus diseases included central and branch retinal vein occlusion, diabetic retinopathy, age-related macular degeneration, central serous choroidopathy and angioid streaks. Analogue images were taken with Kodak Tri-X 35 mm film as well. Although the resolution of the original image was less than that of 35 mm film, it was improved by image processing, particularly contrast enhancement. One type of contrast enhancement, available in both systems, exaggerated lack of light at the peripheral area of the original image. This drawback was not seen with another type of enhancement processing, available in IMAGEnet. However, the latter produced an artificial hypofluorescent area around an intensely hyperfluorescent lesion and also exaggerated hyper- and hypofluorescent patches of the background. Nevertheless, these processing methods were particularly useful in case of media opacity like cataract, even when the 35 mm film picture is not clear. Other processing techniques like pseudocolor and relief, etc. were used just for different ways of presentation. The two systems are basically equivalent, except for contrast enhancement. There was no problem for diagnosis in both systems, but the artificial effects must be borne in mind when interpreting the image.

We describe an efficient solid-phase synthesis of symmetric norbinaltorphimine (norBNI) derivatives 2. Pyrrole formation involving the homocoupling of two solid-supported ketones 6, followed by chemoselective and sequential N-alkylation, provided N-substituted norBNI derivatives 2. Use of this methodology led to the combinatorial synthesis of 120 norBNI derivatives.

C14 YMn2synthesized under high pressure was investigated by NMR technique. It was found that C14 YMn2is paramagnetic down to the lowest temperature, in contrast with the antiferromagnetic ground state found for C15 YMn2. The nuclear spin-lattice relaxation rate of 55Mn in C14 YMn2increases rapidly at low temperatures and tends to saturate above about 50 K, indicating that strong spin fluctuations with antiferromagnetic correlation are rapidly induced on Mn sites by the temperature.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

(KAJIGAESHI , S.; KAKINAMI, T.; MORIWAKI, M.; FUJISAKI, S.; MAE‐ NO, K.; OKAMOTO, T.; Synthesis 1988, 7, 545‐546; Dep.

The reaction of aromatic ethers such as (I) with a stoichiometric amount of benzyltrimethylammonium tribromide in dichloromethane‐methanol gives only mono‐substituted ethers such as (II), whereas in acetic acid‐ZnCl2 di‐ or tri‐substituted ethers such as (III) are selectively obtained in quantitative yields.