Ras-related C3 botulinum toxin substrate 1 (RAC1) regulates glucose-stimulated insulin secretion via modulation of F-actin.

AIMS/HYPOTHESIS: The small G-protein ras-related C3 botulinum toxin substrate 1 (RAC1) plays various roles in mammalian cells, such as in the regulation of cytoskeletal organisation, cell adhesion, migration and morphological changes. The present study examines the effects of RAC1 ablation on pancreatic beta cell function. METHODS: Isolated islets from pancreatic beta cell-specific Rac1-knockout (betaRac1(-/-)) mice and RAC1 knockdown INS-1 insulinoma cells treated with small interfering RNA were used to investigate insulin secretion and cytoskeletal organisation in pancreatic beta cells. RESULTS: BetaRac1(-/-) mice showed decreased glucose-stimulated insulin secretion, while there were no apparent differences in islet morphology. Isolated islets from the mice had blunted insulin secretion in response to high glucose levels. In RAC1 knockdown INS-1 cells, insulin secretion was also decreased in response to high glucose levels, consistent with the phenotype of betaRac1(-/-) mice. Even under high glucose levels, RAC1 knockdown INS-1 cells remained intact with F-actin, which inhibits the recruitment of the insulin granules, resulting in an inhibition of insulin secretion. CONCLUSIONS/INTERPRETATION: In RAC1-deficient pancreatic beta cells, F-actin acts as a barrier for insulin granules and reduces glucose-stimulated insulin secretion.

Effect of intravenous infusion of NIK-716 in anesthetized pediatric patients.

NIK-716 is a maintenance fluid based on the new concept of containing acetate as a base source and 5% glucose as an energy source. It was administered to pediatric patients under general anesthesia for less invasive surgical operations, and its efficacy was investigated by performing blood chemistry examination and urinalysis before and after administration. For efficacy assessment, the three items selected as efficacy parameters, i) the replacement and maintenance of water (assessment of hydration and urine output); ii) the maintenance of serum electrolytes (Na and K); and iii) the utilization of glucose (blood glucose and urinary glucose), were evaluated based on the results of laboratory examination (hematology, blood chemistry and urinalysis), and overall improvement was rated on the basis of total scores of these assessment items. No adverse events or abnormal laboratory values attributable to the maintenance fluid were observed in any of the 25 children administered NIK-716. In an overall improvement rating, NIK-716 proved markedly effective or effective in 79.2% of the 24 children evaluated. The overall safety rating was judged as 'no problem' in all 25 children. These findings suggest that NIK-716 is a useful and safe maintenance fluid that can be administered to pediatric patients during the course of surgery.

Analysis of stiffness and stress in I-bar clasps.

An I-bar clasp is one of the most popular direct retainers for distal-extension removable partial dentures. However, no adequate information is available on the shape associated with biomechanics. This study aimed (1) to establish a three-dimensional (3D) finite-element modelling method of I-bar clasps, and (2) to clarify the effect of the shape on the stress and stiffness of I-bar clasps. 3D computer models of I-bar clasps were created with vertical and horizontal straight sections connected with a curved section with six parameters: thickness of the clasp tip (T), width of the clasp tip (W), radius of the curvature (R), horizontal distance between the base and the vertical axis (H), vertical dimension between the tip and the horizontal axis (V), taper (change of width per unit length along the axis)(Tp). Stress decreased as T, W, R and Tp increased, and as V decreased. Stiffness (which is proportional to retention) increased as T, W, R and Tp increased, and as H and V decreased. In both stress and stiffness, the effects of T and Tp were especially large. From the results, a systematic formula between the clasp shape and the stiffness was derived.

Finite element analysis on preferable I-bar clasp shape.

An I-bar clasp is one of the most popular direct retainers for distal-extension removable partial dentures. However, no adequate information is available on preferable shape as determined by biomechanics. This study aimed (1) to investigate, by finite element analysis (FEA), the dimensions and stress of I-bar clasps having the same stiffness, and (2) to estimate a mechanically preferable clasp design. Three-dimensional FEA models of I-bar clasps were created with vertical and horizontal straight sections connected by a curved section characterized by six parameters: thickness of the clasp tip, width of the clasp tip, radius of the curvature, horizontal distance between the base and the vertical axis, vertical dimension between the tip and the horizontal axis, and taper (change of width per unit length along the axis). Stress was calculated with a concentrated load of 5 N applied 2 mm from the tip of the clasp in the buccal direction. A thinner and wider clasp having an taper of 0.020-0.023 and radius of curvature of 2.75-3.00 showed less stress. The results suggest that such a shape might be the preferable I-bar clasp shape as biomechanical viewpoint.

[All-trans retinoic acid combined with low-dose cytosine arabinoside treatment for acute myelogenous leukemia with trilineage myelodysplasia--a case report].

AML with trilineage myelodysplasia (AML/TMDS) is recognized as having of poor prognosis due to its resistance to chemotherapy in comparison with de novo AML. An AML/TMDS patient who failed to respond to ordinary induction therapy achieved complete remission with combination therapy consisting of all-trans retinoic acid (ATRA) and low-dose Ara-C. No serious toxicity was observed. ATRA combined with low-dose Ara-C could be an alternative treatment for this kind of patient.

Acute lymphoblastic leukemia accompanied by chromosomal abnormality of translocation (12;17).

This report concerns a female patient with B-precursor acute lymphoblastic leukemia with concomitant expression of CD13 and CD33. A rare chromosomal abnormality, t(2;17)(p13:q21), was detected in 70% of metaphases analyzed. A new subgroup of acute leukemia is proposed, consisting of our case and 12 reported cases with similar chromosomal abnormalities. This subgroup has a poor prognosis and a high incidence of biphenotypic characteristics.

Dimensional measurement and finite element analysis of I-bar clasps in clinical use.

An I-bar clasp is a popular retainer for distal-extension removable partial dentures. However, there have been almost no evidence-based criteria on the mechanically preferable shape. The present study aimed to investigate the variations of dimension in I-bar clasps used in patients, and to clarify the effect of the variations on stiffness and stress of I-bar clasps by finite element analysis. Dimensions (thickness, width, taper, radius of curvature, length, relation to oral structures) of 23 I-bar clasps were measured. A three-dimensional finite element model was made for each measured I-bar clasp with vertical and horizontal straight sections connected with a curved section. A concentrated load of 5 N was applied at the lowest point of the tip that contacted the abutment in the buccal direction. Maximal equivalent stress and stiffness of each clasp were evaluated. The measured dimension, stiffness, and maximum stress showed wide variations. Mean stiffness was far from the proper one, and mean stress was near the proportional limit of Co-Cr alloy. Considering the stiffness and stresses in this study, only six clasps out of 23 were appropriate. These results suggest that evidence-based criteria of preferable shape of I-bar clasps should be determined.

The rat intrinsic factor gene: its 5'-upstream region and chief cell-specific transcription.

A DNA segment containing the 5'-upstream region and amino terminal reading frame of the gastric intrinsic factor gene was cloned from rat and its nucleotide sequence was determined. S1 mapping demonstrated that the transcription initiation site is located downstream of the second TATA-box sequence. Similar sequence motifs to those in the pepsinogen genes transcribed in gastric chief cells were found in the deduced sequence, suggesting that the rat intrinsic factor gene is transcribed in these cells. The genes for the intrinsic factor and its homologous protein transcobalamin I were apparently derived from a common ancestoral gene, since the positions of their intron insertions as well as the amino acid residues are conserved. Northern blot hybridization showed that the gene for the intrinsic factor is transcribed in the stomach but not detectably in the intestine, kidney, testis, brain, heart, liver, lung, or spleen. In situ hybridization using radioactive complementary RNA clearly indicated that the major transcription site in gastric glands is chief cells. Different locations of expression of intrinsic factor proteins in various mammals were observed previously using antibodies: in rat parietal cells and chief cells, in mouse chief cells, and in human parietal cells. The present results clearly demonstrated the intrinsic factor mRNA mainly in chief cells of adult rats, as in mice, suggesting that transcriptional regulation of the intrinsic factor gene is essentially the same in rodents.

The use of the laryngeal mask airway in pediatric anesthesia.

Laryngeal mask airway (LMA) insertion was tried in 120 pediatric cases, from 2 months to 12 years of age. Initial indications for LMA were the same as for a face mask, except for two additional conditions; anticipation of difficulty with intubation and difficulty in management by a face mask. Size 2 LMA was used in the vast majority of cases. The insertion was successful on the first trial in 108 cases. More than one trial was necessary in 9 cases but only 3 cases required more than 3 trials. Insertion could not be completed in 3 cases. The relationship between the depth of LMA at the front teeth and age could be roughly described by "depth = 10 cm + 0.3 x Age". LMA was found to provide a better and more secure airway than the face mask without direct tracheal intervention. Heart rate did not increase with LMA insertion. It is easy to use and can be used in place of the face mask, but complications such as stomach air inflation due to too vigorous manual ventilation, slight pharyngeal injury, and airway obstruction due to kinking of LMA can occur. These complications can be avoided and must be kept in mind during it's use. LMA itself can be used to obtain a patent airway where an endotracheal airway is difficult to obtain. LMA-aided tracheal intubation can be extremely useful in obtaining endotracheal airways. Non-blind techniques can be used with LMA to increase safety. LMA is a very useful addition to pediatric anesthesia practice.

[Experimental study on a mechanical root canal enlargement].

It is difficult for us to enlarge a root canal by using hand-instruments in a molar tooth, so we experimented by using mechanical equipment. We examined the human extracted premolar which we had preserved in physiological saline solution by using a speculative root canal enlarging machine. Then we observed the time and condition of enlarging root canal by X-ray. After slicing off, we examined with our eyes and with an electronic microscope. Afterward, we compared hand-instruments with the enlarging machine. As the results of this experiment; 1. Time by hand filing instruments took three or four times to make a root canal enlargement by a speculative enlarging machine. 2. After enlarging a root canal, we made a root canal filling. Observing them by X-ray and ground specimen, we recognized a good result in the root canal enlargement and in the condition of the root canal filling. 3. Observing the figure by electronic microscope, in the case of using a speculative machine, we found that the slicing aspects of dentin which had been enlarged by root canal were thoroughly smoothed in the center part of the root canal, but it was not smoothed in the root apex region. 4. It had a tendency to remain part of the cutting dentin near the apical area both by using hand cutting instruments and by using a speculative machine.