Hepatic necrosis with cholestasis induced by long-term voglibose administration.

A 76-year-old woman admitted to our hospital for jaundice had been treated for diabetes mellitus with insulin for 9 years and voglibose had been added for the 39 months preceding admission. Elevated serum bilirubin and transaminase concentration began to normalize with initiation of corticosteroid treatment 1 week after discontinuation of voglibose. In the in vitro testing of the patient's peripheral blood, lymphocytes showed stimulation by voglibose. In dramatic contrast to an initial liver biopsy specimen that demonstrated cholestasis with submassive and zonal necrosis, the follow-up specimen was normal 1 year later. We believe that patients treated with voglibose should be monitored long-term with monthly determinations of transaminases and bilirubin in serum.

Crystallization and preliminary X-ray analysis of chondroitin sulfate ABC lyases I and II from Proteus vulgaris.

Chondroitin sulfate ABC lyases (E.C. 4.2.2.4) are broad-specificity glycosaminoglycan-degrading enzymes. Their preferred substrates are chondroitin sulfate and dermatan sulfate, which are broken down to short oligosaccharides. Proteus vulgaris produces two such lyases, ABC lyase I and II, with molecular weights of 112-113 kDa. Diffraction-quality crystals of both enzymes have been obtained by the hanging-drop vapour-diffusion method. ABC lyase I crystallizes in space group P2(1)2(1)2(1), with unit-cell parameters a = 49.3, b = 95.1, c = 230.0 A, Z = 4, and diffracts to 1.9 A resolution. Crystals of ABC lyase II belong to space group P1, with unit-cell parameters a = 64.2, b = 64.3, c = 142.1 A, alpha = 95.7, beta = 98. 1, gamma = 95.5 degrees, Z = 2; diffraction extends to at least 2.1 A.

Substrate specificity studies of Flavobacterium chondroitinase C and heparitinases towards the glycosaminoglycan--protein linkage region. Use of a sensitive analytical method developed by chromophore-labeling of linkage glycoserines using dimethylaminoazobenzenesulfonyl chloride.

Bacterial chondroitinases and heparitinases are potentially useful tools for structural studies of chondroitin sulfate and heparin/heparan sulfate. Substrate specificities of Flavobacterium chondroitinase C, as well as heparitinases I and II, towards the glycosaminoglycan-protein linkage region -HexA-HexNAc-GlcA-Gal-Gal-Xyl-Ser (where HexA represents glucuronic acid or iduronic acid and HexNAc represents N-acetylgalactosamine or N-acetylglucosamine) were investigated using various structurally defined oligosaccharides or oligosaccharide-serines derived from the linkage region. In the case of oligosaccharide-serines, they were labeled with a chromophore dimethylaminoazobenzenesulfonyl chloride (DABS-Cl), which stably reacted with the amino group of the serine residue and rendered high absorbance for microanalysis. Chondroitinase C cleaved the GalNAc bond of the pentasaccharides or hexasaccharides derived from the linkage region of chondroitin sulfate chains and tolerated sulfation of the C-4 or C-6 of the GalNAc residue and C-6 of the Gal residues, as well as 2-O-phosphorylation of the Xyl residue. In contrast, it did not act on the GalNAc-GlcA linkage when attached to a 4-O-sulfated Gal residue. Heparitinase I cleaved the innermost glucosaminidic bond of the linkage region oligosaccharide-serines of heparin/heparan sulfate irrespective of substitution by uronic acid, whereas heparitinase II acted only on the glucosaminidic linkages of the repeating disaccharide region, but not on the innermost glucosaminidic linkage. These defined specificities of chondroitinase C, as well as heparitinases I and II, will be useful for preparation and structural analysis of the linkage oligosaccharides.

A study to evaluate the parent-offspring similarity in the maxillofacial profile using fingerprints in Japanese families.

An attempt was made to investigate the parent-offspring similarity in the maxillofacial profile by a quantitative analysis of fingerprints. Lateral roentgenographic cephalograms and ten fingerprints were obtained from 98 Japanese patients (44 males and 54 females) and their parents. Analysis showed a significant parent-offspring correlation for both maxillofacial profile and fingerprints. The relatively low father-son correlation for both features suggests a major influence of X-linked genes. The genetic correlation between the maxillofacial profile and fingerprints was significant for parent-son but not for parent-daughter pairings. The parent-offspring correlation in the maxillofacial profile was evaluated in two groups showing differences (distant group) or similarities (near group) in the fingerprint patterns between the father and mother. In the distant group, a greater parent-offspring similarity was observed in the maxillofacial profile. The same finding was also obtained on using only digit II of the parents. Therefore, from a morphogenetical point of view, parental fingerprints appear helpful in clinical applications designed to predict maxillofacial growth in offspring.

The similarity between parents and offspring in facial soft tissue: a frontal-view study.

Similarities between parents and their offspring in facial soft tissue features were investigated. Fifty boys and fifty girls aged 9-10 years, excluding those with congenital anomalies, were selected. Frontal photographs of the family (father, mother and offspring) were taken and twenty-nine landmarks located on each enlarged tracing made from a photograph. Each landmark was digitised into (x, y) co-ordinate values from which the area and linear ratio dimensions were calculated and statistically evaluated. Results indicated that: (1) The nose was the feature that was most significantly correlated between parents and offspring. (2) The similarities between parents and offspring were closer for the relative positions of other features to the eyes than for individual features of the face. In general, the correlations between 'midparents' (the mean value of both parents) and offspring were higher than those between one parent and offspring. (3) The correlations between parents and offspring for size were higher than those for shape. (4) The similarities between mothers and offspring were closer than those between fathers and offspring. Furthermore: among four pairs of father/son, father/daughter, mother/son and mother/daughter, the mother/daughter pair had the highest correlation and the father/son pair had the lowest, which appears to be related to X-chromosome inheritance.

Preparation of unsaturated disaccharides by eliminative cleavage of heparin and heparan sulfate with heparitinases.

1. Six kinds of unsaturated disaccharides were prepared by enzymatic digestion of heparin and heparan sulfate with heparitinases I0 and IV, and subsequent column chromatography. They were identified by HPLC showing good separation from each other. 2. The content of each unsaturated disaccharide fraction was determined colorimetrically, and found to range from 130.7 to 722.3 mumol. 3. Molecular extinction coefficient of each unsaturated disaccharide was calculated from absorbance at a wavelength of around 230 nm where a peak appeared on the ultraviolet spectrum of each disaccharide solution at pH 2. The values varied from 6000 to 6600.

Use of the stomach as an esophageal substitute.

Esophagoplasty with isoperistaltic stomach is a useful and satisfactory means of reconstruction of the esophagus. It is simpler and there is no necessity for using a reversed gastric tube. The most essential points of technique for the modelling of the stomach, is taking advantage of the ample intramural vascular network and adequate selection of the highest point of the stomach for the site of the esophago-or pharyngogastrostomy. To utilize the intramural vascular network, sufficient width of the stomach is necessary. This also allows stretching of the stomach. Esophageal resection and reconstruction using the isoperistaltic stomach above the level of the neck was performed on 130 cases. Among them 40 cases were pharyngogastromies and 90 cases were cervical esophagogastromies. There was one operative death due to alcoholic liver cirrhosis (operative mortality rate 0.8%). If the stomach is properly handled, esophageal replacement by the isoperistaltic stomach gives constant success.