Novel Functional Peptide for Next-Generation Vital Pulp Therapy.

Although vital pulp therapy should be performed by promoting the wound-healing capacity of dental pulp, existing pulp-capping materials were not developed with a focus on the pulpal repair process. In previous investigations of wound healing in dental pulp, we found that organic dentin matrix components (DMCs) were degraded by matrix metalloproteinase-20, and DMC degradation products containing protein S100A7 (S100A7) and protein S100A8 (S100A8) promoted the pulpal wound-healing process. However, the direct use of recombinant proteins as pulp-capping materials may cause clinical problems or lead to high medical costs. Thus, we hypothesized that functional peptides derived from recombinant proteins could solve the problems associated with direct use of such proteins. In this study, we identified functional peptides derived from the protein S100 family and investigated their effects on dental pulp tissue. We first performed amino acid sequence alignments of protein S100 family members from several mammalian sources, then identified candidate peptides. Next, we used a peptide array method that involved human dental pulp stem cells (hDPSCs) to evaluate the mineralization-inducing ability of each peptide. Our results supported the selection of 4 candidate functional peptides derived from proteins S100A8 and S100A9. Direct pulp-capping experiments in a rat model demonstrated that 1 S100A8-derived peptide induced greater tertiary dentin formation compared with the other peptides. To investigate the mechanism underlying this induction effect, we performed liquid chromatography-tandem mass spectrometry analysis using hDPSCs and the S100A8-derived peptide; the results suggested that this peptide promotes tertiary dentin formation by inhibiting inflammatory responses. In addition, this peptide was located in a hairpin region on the surface of S100A8 and could function by direct interaction with other molecules. In summary, this study demonstrated that a S100A8-derived functional peptide promoted wound healing in dental pulp; our findings provide insights for the development of next-generation biological vital pulp therapies.

Successful reduced-intensity SCT from unrelated cord blood in three patients with X-linked SCID.

We describe three males with X-linked SCID (X-SCID) who were successfully treated by reduced-intensity SCT from unrelated cord blood (CB). Mean age at transplant was 5.7 months (range, 3-9 months). Pre-transplant conditioning for all patients consisted of fludarabine (FLU) (30 mg/m(2) per day) from day -7 to day -2 (total dose 180 mg/m(2)) and BU 4 mg/kg per day from day -3 to day -2 (total dose 8 mg/kg). All CB units were serologically matched at HLA-A, B and DR loci. Although two patients had suffered from fungal or bacterial pneumonia before transplantation, there were no other infectious complications during transplantation. All patients engrafted and achieved 100% donor chimerism. We also confirmed full donor chimerism of both T and B cells. Only one patient developed acute GVHD grade III, which was resolved by increasing the dose of oral corticosteroid. None of the patients has developed chronic GVHD during follow up for 21-77 months. None of the patient received i.v. Ig replacement post transplant, or showed delay in psychomotor development. Reduced-intensity conditioning consisting of FLU and BU and transplantation from unrelated CB was an effective and safe treatment for these patients with X-SCID.

Length determination of vessel elements in tree trunks used for water and nutrient transport by Fourier transform Raman spectroscopy.

Length analysis of vessel elements in tree trunks used for water and nutrient transport is a lengthy, multistep procedure although it reflects environmental stresses on a tree. The feasibility of using FT-Raman spectroscopy for rapid determination of vessel element length in a tree was examined using wood powders of two Eucalyptus species, including samples of various ages and colors. The first-derivative transformation followed by the multiplicative scatter correction of Raman spectroscopic data and the partial least-squares regression revealed highly significant correlation between conventionally measured and Raman-predicted vessel element length with correlation coefficients (r) of 0.843 and 0.826, respectively, in the calibration (for known samples, n = 186) and in the prediction (for unknown samples, n = 40). FT-Raman spectroscopy coupled with multivariate data analysis will contribute to solving the interactions between emerging environmental issues and the anatomical structure of wood, which allow efficient management practices in growing forests to fix atmospheric CO(2) effectively.

High correlation between results of the [1-13C]-phenylalanine breath test and phenylalanine hydroxylase (EC 1.14.16.1) activity of the liver in rats.

BACKGROUND: (13)CO(2) is decreased in patients with end-stage liver disease by the [1-(13)C]-phenylalanine breath test. Decreased (13)CO(2) is supposed to be caused by the decreased ability of the liver to oxidize phenylalanine. However, no direct evidence has been reported. METHODS: The [1-(13)C]-phenylalanine breath test was performed in galactosamine hepatitis rats (n = 14) and control rats (n = 8). Plasma phenylalanine concentration before intravenous administration of [1-(13)C]-phenylalanine, the elimination rate of phenylalanine and the phenylalanine hydroxylase (PAH; EC 1.14.16.1) activity of the whole liver were examined. RESULTS: Increase of (13)CO(2) in the breath [Delta(13)CO(2) ( per thousand)] of galactosamine hepatitis rats 2 min after administration of [1-(13)C]-phenylalanine was only 1/5 of that in control rats. The concentration of plasma phenylalanine and the elimination rate of plasma phenylalanine in hepatitis rats did not show significant differences compared to control rats. On the other hand, a clear difference in the activity of PAH was observed between hepatitis rats and control rats. Delta(13)CO(2) ( per thousand) 2 min after administration of [1-(13)C]-phenylalanine was highly correlated to the PAH activity of the whole liver (r = 0.917). CONCLUSION: It was strongly indicated that decreased Delta(13)CO(2 ) in hepatitis rats was the result of decreased activity of PAH.

In situ determination of proportion of cell types in wood by Fourier transform Raman spectroscopy.

Analysis of the proportion of cell types in native wood is important for understanding the environmental stresses including an increasing atmospheric CO2 concentration on the structure of wood, especially for the management of plantation forests which will reduce our reliance on natural forests. The conventional method for determining the proportion of cell types is a quantitative microscopy, which is one of the image analyzing systems using a light microscope combined with a microcomputer. However, it is a lengthy multistep procedure. We have examined the feasibility of using Fourier transform Raman spectroscopy for rapid determination of proportion of cell types (fiber, ray parenchyma, vessels, and axial parenchyma) in native wood with using wood meals of two Eucalyptus species, including samples of various ages and colors. By the application of second derivative transformation of Raman spectroscopic data and the partial least-squares regression, we have successfully obtained highly significant correlations between microscopically measured and Raman predicted values for all traits except vessels with correlation coefficients of >0.9 and 0.8, respectively, in the calibration and in the prediction. This method is valid for all traits since vessels can be calculated by the rest of three traits, and will help to solve the effect of the environmental issues on trees and the supplement of renewable raw materials.

Evans' syndrome associated with Graves' disease.

A 36-year-old woman who had had Graves' disease for 6 years was admitted with severe thrombocytopenia. Evans' syndrome was diagnosed. The patient's family history showed multiple cases of Graves' disease but no cases of Evans' syndrome. Both conditions in this patient improved with corticosteroid and thiamazole therapy. Several autoimmune antibodies were found, but a common autoimmune mechanism was not clearly shown. Although the combination of Graves' disease and Evans' syndrome had not occurred previously in her family, genetic factors may play an important role in the pathogenesis of both conditions.

[A case of early syphilis presenting general paresis-like symptoms and bilateral tonic pupils].

A 40-year-old man was admitted after 8 months of speech disturbance and locomotive ataxia. He had no seizures, lightning pains, paresthesia, visual loss, bladder disturbance or rectal incontinence. He had never been neurologically or psychiatrically ill and had no history of syphilis. When the patient was admitted, his general physical examination including blood pressure and dermatologic examination was normal. His consciousness was alert. He was found to have a deterioration of mental status such as inability to concentrate, failing memory, amnesia and circumstantiality. His pupils were anisocoric and Achilles jerks were absent. No rigidity of the neck muscles, paralysis and sensory disturbance were recognized. Romberg's sign was absent. The right pupil was 7.0 mm and the left was 6.0 mm in room illumination. The pupils were nonreactive to bright light and both did not constricted to near stimuli. 0.125% pilocarpine eyedrops produced bilateral pupillary constriction. The results indicated bilateral tonic pupils. Laboratory data revealed white cell count of 12,600/mm3 and normal erythrocyte sedimentation rate of 8 mm/hr. Cerebrospinal fluid (CSF) examination revealed the following: opening pressure, 140 mm of water; cell counts, 76/mm2 (mononuclear cells); total protein, 116 mg/dl; glucose, 57 mg/dl. A serum venereal disease research laboratories (VDRL) test was positive in a 1:32 titer confirmed by positive treponema pallidum hemagglutination (TPHA) test in a 1:40,960 titer and positive fluorescent treponemal antibody-absorption (FTA-ABS) test. Serum TPHA-IgM was positive in a 1:320 titer but TPHA-IgG was negative. CSF examination revealed positive TPHA test (titer of 1:2,560) and positive FTA-ABS test.(ABSTRACT TRUNCATED AT 250 WORDS)

Unusual mode of inhibition of Citrobacter freundii beta-lactamases by ceftriaxone.

Several Citrobacter freundii beta-lactamases, discernible by their substrate profiles and sensitivities to inhibition by newer cephalosporins, were inhibited by ceftriaxone in an unusual manner. Inhibition was noncompetitive at low concentrations of cephaloridine but became competitive at concentrations above 600 muM, which is close to the K(m) (570 muM) for cephaloridine.

In vitro potentiation of cephalosporins by alafosfalin against urinary tract bacteria.

Potentiating activity of alafosfalin was examined in detail with 8 cephalosporins and mecillinam against 164 urinary bacteria representing 8 genera. Alafosfalin was generally comparable in activity to cefamandole and mecillinam but superior to other cephalosporins tested. When the minimal fractional inhibitory concentration indices were compared, synergism was observed with all of the beta-lactams tested for all species except Streptococcus faecalis. Marked synergism was observed with Escherichia coli, Citrobacter, and enterobacter and, among the drugs tested, with cefamandole and mecillinam. Although alafosfalin is inactive against Pseudomonas aeruginosa, potentiation was seen with cefsulodin. The most favorable combination ratio of alafosfalin/cephalosporin to elicit potentiation was determined for each species and occurred in a rather narrow range of combinations (1:4 to 4:1 in general).