Major quantitative trait locus on chromosome 2 for glucose tolerance in diabetic SMXA-5 mouse established from non-diabetic SM/J and A/J strains.

AIMS/HYPOTHESIS: The SMXA-5 mouse is one of the SMXA recombinant inbred substrains established from the non-diabetic SM/J and A/J strains, and is a model for polygenic type 2 diabetes, characterised by moderately impaired glucose tolerance and hyperinsulinaemia. These diabetic traits are worsened by feeding a high-fat diet. The aim of this study was to dissect the diabetogenic loci in the A/J regions of the SMXA-5 genome that contribute to diabetes-related traits. MATERIALS AND METHODS: We analysed the quantitative trait loci (QTL) for diabetes-related traits and obesity in (SM/JxSMXA-5)F(2) intercross mice fed a high-fat diet. To verify the function of the responsible locus that was mapped in the present study, we constructed a congenic strain and characterised its diabetes-related traits. RESULTS: A major QTL for glucose tolerance, free-fed blood glucose concentration and BMI was mapped on chromosome 2. This locus existed near D2Mit15, with the highest logarithm of the odds score (12.6) for glucose concentration at 120 min in a glucose tolerance test, and was designated T2dm2sa. The diabetogenic allele of T2dm2sa originated in the A/J strain. SM.A-T2dm2sa, a congenic strain that introgressed the T2dm2sa region of A/J genome into SM/J, exhibited overt impaired glucose tolerance and hyperinsulinaemia. CONCLUSIONS/INTERPRETATION: The development of impaired glucose tolerance in SM.A-T2dm2sa mice confirmed the results of QTL analysis for diabetes-related traits in F(2) intercross mice. The present results suggest that there are latent diabetogenic loci in the genomes of non-diabetic A/J and SM/J mice, and that the coexistence of these loci, including T2dm2sa, causes impaired glucose tolerance in SMXA-5 and SM.A-T2dm2sa mice.

Mosaicism and phenotype in ring chromosome 20 syndrome.

Ring chromosome 20 [r(20)] syndrome is a rare chromosomal disorder characterized by epilepsy, mild to moderate mental impairment, and malformation. Patients generally show mosaicism in 1-100% of lymphocytes with r(20). We report here a patient with r(20) syndrome who exhibited mild phenotype with the small ratio of mosaicism (13%) with r(20). Although previous small-scale studies concluded that the mosaicism ratio was unrelated to clinical phenotype, our reassessment of all 57 reported cases has revealed that the ratio is significantly associated with age at seizure onset, intelligence quotient, and malformation, but not with the response of epilepsy to drug treatment. Our results provide important clinical information and prediction for r(20) syndrome.

Periapical lesions in rats with streptozotocin-induced diabetes.

The purpose of this study was to investigate histologically and histometrically the changes in pulpal periapical tissues after pulpal exposure in streptozotocin-induce diabetic rats. Control rats were injected with citrate buffer. Experimental rats were injected with streptozotocin dissolved in citrate buffer. All animals received a pulpal exposure in the left mandibular first molar. Blood glucose concentration was measured at, 0, 7, 14, 28, and 42 days. All animals were killed at 7, 14, 28, and 42 days after pulpal exposure, and their mandibles were evaluated histologically and histometrically. Blood glucose levels in the experimental rats were significantly higher than those in the control rats. In experimental rats, inflammation in the apical periodontal ligament and root resorption and alveolar bone resorption were more severe than that in control rats. This study also revealed histometrically that, in experimental rats, lesions in the periapical area were significantly larger than those in control rats.

Effect of traumatic occlusion on periapical lesions in rats.

The effect of traumatic occlusion on periapical lesions in rats was investigated histologically and histometrically. Rats were divided equally into groups A to D. Rats in group A received no treatment; in group B, rats received pulpal exposure of the left mandibular first molar; in group C, a resin plate was cemented onto the occlusal surface of the corresponding maxillary molar; and in group D, the molar pulp was exposed and the resin plate was installed. At 1 and 2 wk, compression of the periodontal ligament and inflammation were less in group D than in group B. Lesions in the periapical periodontal ligament at 1, 2, and 4 wk in group D were significantly smaller than those in group B. This study suggests that traumatic occlusion delayed the enlargement of the periapical lesions in rats.

Effect of methotrexate-induced neutropenia on rat periapical lesion.

We investigated the effect of methotrexate-induced neutropenia on periapical lesions in rats. Periapical lesions were prepared in all animals by pulpal exposure. The animals were injected with methotrexate three times a week 4 weeks before or after the pulpal exposure. The periapical lesion of each animal was examined histologically, histometrically, and immunohistochemically. The total leukocyte count and neutrophil count in the peripheral blood decreased after the injection. The methotrexate-induced neutropenia elicited after pulpal exposure did not change the status of the periapical lesion, whereas the neutropenia before the exposure inhibited the development of the lesion. Moreover, the neutropenia before pulpal exposure resulted in an inhibition of infiltration of neutrophils into the lesion.

Pulpal and periapical tissue reactions after experimental pulpal exposure in rats.

The purpose of this study was to investigate histologically and histometrically the changes in pulpal and periapical tissues after pulpal exposure in rats. All animals received a pulpal exposure in the left mandibular first molar. Animals were killed at 1 to 56 days after pulpal exposure, and their mandibles were evaluated histologically and histometrically. Histologically, pulpal necrosis extended gradually from the upper part of the pulpal tissue to the apex, with inflammation starting in the periapical tissue at an early stage. As the periapical lesion developed, alveolar bone and cementum resorption was also found. Histometrically, the length of pulpal necrosis increased gradually from 1 to 28 days. The vertical length of the periapical lesion after 14 days was significantly increased, while the horizontal length and the overall area after 7 days were also significantly increased. The periapical lesion extended in a mesiodistal direction at first and then in a vertical direction before expansion ceased.

[Studies on as-triazine derivatives. XIX. Synthesis of 2,3-diarylpyrazine 2,3-diarylpyridine derivatives as blood platelet aggregation inhibitors].

4,5-Diphenyl-2-ethoxypyrimidine (1), 3,4-diphenyl-6-ethoxypyridazine (2) and 2,3-diphenyl-5-ethoxypyrazine (3) were evaluated for inhibitory activity towards arachidonic acid-induced aggregation of rabbit blood platelet in vitro. 2,3-Diphenyl-5-ethoxypyrazine (3) exhibited significant inhibitory activity. Thus, various 5-substituted 2,3-bis(4-methoxyphenyl)pyrazines were synthesized by the nucleophilic substitution reaction of 5-chloro-2,3-bis(4-methoxyphenyl)pyrazine (9). In a similar manner, substituted 2,3-bis(4-methoxyphenyl)pyridines were prepared from 2,3-bis(4-methoxyphenyl)-6-methylsulfonylpyridine (17), which was synthesized by the cycloaddition retro Diels-Alder reaction of 5,6-bis(4-methoxyphenyl)-3-methylsulfonyl-1,2,4-triazine (16) with norbornadiene. Among the compounds prepared, 6-isopropoxy-2,3-bis(4-methoxyphenyl)-pyrazine (10f) showed the most potent inhibitory activity, which was more than the activity of anitrazafen[5,6-bis(4-methoxyphenyl)-3-methyl-1,2,4-triazine.

Endotoxin and gram-negative bacteria in the rat periapical lesions.

The purpose of this study was to measure the amount of endotoxin as well as to identify Gram-negative bacteria in experimental periapical lesions in rats. Molar pulps were exposed and infected and the amount of endotoxin in the periapical tissue of the right mandibular first molar was measured by Endospecy, while the colony number of Gram-negative bacteria was determined in the same region of the left mandibular first molar. In the control animals, the amount of endotoxin in the periapical tissues did not change at all during the experimental period, and no Gram-negative bacteria were isolated. In the experimental animals, the amount of endotoxin in the periapical tissues increased gradually from 1 to 70 days, and its level was significantly greater than that of control animals after 7 days. Gram-negative bacteria were isolated from the periapical tissues and their number gradually increased from 1 to 14 days (26 to 82%), but decreased at 21 days. It was approximately 60% from 28 to 70 days. The results of this study showed that the amount of endotoxin in the periapical tissues gradually increased with increasing time and that Gram-negative bacteria were isolated from the same region but did not increase in number concurrently with the increase in the amount of endotoxin.

A possible relationship between cord blood transferrin and birth length in infants.

Cord blood levels of transferrin (Tf) and insulin-like growth factor I (IGF-1) were measured in 33 normal and 12 preterm infants. Tf was measured by the single radial immunodiffusion technique, while IGF-1 was measured by specific RIA. Tf levels in normal term infants (195 +/- 27 mg/dl) were significantly below normal adult levels (261 +/- 12 mg/dl). Tf levels in preterm infants (159 +/- 30 mg/dl) were lower than those in normal term infants. Tf levels showed a positive correlation with birth length, weight, gestational age and albumin levels in all infants. There was no correlation between Tf and IGF-1 levels in term and preterm infants.

Transferrin receptor on rat Kupffer cells in primary culture.

Kupffer cells may play a role in the turnover of iron in acute viral hepatitis. The transferrin receptor of rat Kupffer cells in primary culture was therefore investigated in this study. Daily specific bindings on 125I-diferric transferrin (Tf) to rat Kupffer cells in primary culture from day 3 to day 6 of culture were 1.64 +/- 0.08%, 4.16 +/- 0.05%, 4.34 +/- 0.07% and 2.63 +/- 0.07%, respectively. The specificity of the Tf binding sites was examined by competition studies showing that galactose (30 mmol x l-1) and ovalbumin (90 mumol x l-1) did not compete for the binding sites, but human lactoferrin (50 mumol x l-1) competed for the binding sites by about 30%. The affinity and capacity of Tf receptor on rat Kupffer cells in 5-day culture were analyzed according to the method of Scatchard. A single class of 125I-diferric Tf binding sites with an affinity constant of 1.65 x 10(7) l x l-1) and a capacity of 6.86 x 10(6) sites/cell was found. After zymosan (500 micrograms/ml) preincubation for 30 min, the binding capacity increased about 1.7-fold, and this increase depended upon the increase of the affinity of Tf receptor. These data suggest that Kupffer cells in the activated state accelerate the removal of elevated serum iron.

Single-crystal elastic properties of the modified spinel (Beta) phase of magnesium orthosilicate.

The single-crystal elastic moduli of the modified spinel structure (beta phase) of magnesium orthosilicate (Mg(2)SiO(4)) have been measured by Brillouin spectroscopy under ambient conditions. Single crystals with dimensions up to 500 micrometers were grown at 22 gigapascals and 2000 degrees C over a period of 1 hour. Growth of crystals larger than 100 micrometers was achieved only when the pressure was within 5 percent of the pressure of the phase boundary separating the beta- and gamma-phase stability fields. A comparison of the elastic properties of the modified spinel phase with those of the olivine phase suggests that the 400-kilometer seismic discontinuity in the earth's mantle can be described by a mantle with 40 percent olivine. These results confirm that the 400-kilometer discontinuity can be due to the transition from olivine to modified spinel. The amount of olivine that must be present is less than that in a pyrolite model, although the results do not exclude pyrolite as a possible mantle model.