Biomedical subjects
Publications and source records attributed to K Sakaguchi.
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INTRODUCTION: We synthesized sulfo-glycolipid, beta-SQAG9 (designate square beta-SQAG9 liposome, because it efficiently forms a liposome structure) that possessed immunosuppressive effects such as inhibition of T-cell responses in human allogeneic MLR and skin allograft survival in rats, and bound to CD62L (L-selectin) in vitro. In this study, we further investigated the immunosuppressive mechanism in vivo by beta-SQAG9 liposome in a skin-allografted rat model. METHODS: ACI rats (RT1(a)) were grafted skin of LEW rats (RT1(1)) treated with PBS or beta-SQAG9 liposome IV once a day for 7 days. Subsequently, we investigated the population of T cells and CD62L(+) T-cell subset in the spleen, axillary lymph nodes (ALNs), and peripheral blood of skin-allografted rats by two-color flow cytometry. RESULTS: Five of 11 (45.5%) rats that were treated with 50 mg/kg beta-SQAG9 liposome showed graft survival and another showed moderate rejection in graft. The CD62L(+) T-cell subset population in ALNs of beta-SQAG9 liposome-treated rats decreased in a dose-dependent manner. No significant difference in the T-cell population was observed between the beta-SQAG9 and control groups. These data suggest that beta-SQAG9 could bind to the CD62L(+) T-cell subset in vivo as well as in vitro and affect T-cell migration, which might lead to T-cell tolerance in vivo.
K1 killer toxin secreted by the K1 strain of Saccharomyces cerevisiae, has been well characterized. It is a simple protein of molecular weight (MW) 11,470 (ref. 3), encoded by a double-stranded, linear RNA plasmid, called M RNA, of MW 1.1-1.7 x 10(6) (refs 4-6). It is lethal to sensitive Saccharomyces cerevisiae which does not carry M RNA. Leakage of K+ and ATP is the first distinct response in sensitive cells, and the toxic action is thought to be due to its action as a protonophore or K+ ionophore. Recently, a further killer toxin has been found in Kluyveromyces lactis IFO 1267, and it is associated with the presence of the double-stranded linear DNA plasmids, pGK1-1 (MW 5.4 x 10(6)) and pGK1-2 (MW 8.4 x 10(6)). It has been shown, by curing pGK1-1 or deletion mapping, that the structural gene for the killer toxin and immunity-determining gene reside on the smaller plasmid. Moreover, the plasmids could be transferred from K. lactis to S. cerevisiae by protoplast fusion and protoplast transformation. As the K. lactis toxin is encoded by a DNA plasmid and has a relatively wider action spectrum than K1 killer toxin, the mode of action of the toxin is highly interesting. Here we report that K. lactis toxin inhibits adenylate cyclase in sensitive yeast cells and brings about arrest of the cells at the G1 stage.
The nasal surface basophilic metachromatic cells increase in allergic rhinitis and play an important role in the manifestation of nasal symptom. Their numbers were decreased in good correlation with the severity of symptom and nasal provocation reaction after clinical treatment with specific immunotherapy or topical steroid, beclomethasone dipropionate. The percentages of allergen induced histamine release from these cells were not changed after clinical treatment with cromolyn sodium.
BACKGROUND/AIMS: We investigated the prevalence of hepatitis G virus infection among inhabitants of a hepatitis C virus endemic area. METHODOLOGY: Two hundred and eighty-eight inhabitants, who underwent medical examinations for health screening, were enrolled in this epidemiological study. HGV RNA and HCV RNA were detected by polymerase chain reaction. We also examined anti-HGV envelope protein (E2) antibodies in all serum samples. RESULTS: In these 288 inhabitants, we found anti-HCV antibodies (HCV-Ab) and HCV RNA in 28.5% and 17.4%, respectively. HGV RNA and anti-HGV E2 were detected in 9 (3.1%) and 16 (5.5%), respectively. One patient was positive for both HGV RNA and anti-HGV E2. The exposure rate, expressed as the percentage of people with HGV RNA and/or anti-HGV E2, was 8.3%, which was significantly lower than the incidence of positive HCV-Ab. Of the 24 patients with HGV RNA and/or anti-HGV E2, 15 (62.5%) were positive for HCV-Ab, of those HCV RNA was detected in 9 (37.5%). Further, we found a higher prevalence of HGV exposure in patients with HCV-Ab than in those without (8.3% vs. 4.4%). CONCLUSIONS: HGV infection was not identical to the epidemic hepatitis C virus infection among inhabitants of this town, suggesting that hepatitis C virus might be less infectious than hepatitis C virus.
PURPOSE: Expeditious postoperative ingrowth of bone into dental implants is desired for clinically successful fixation of oral implants. The present study was performed to evaluate the effect of applying a capacitively coupled electric field (CCEF) on periimplant osteogenesis in the dog mandible. MATERIALS AND METHODS: Twelve adult male beagles were used in this study. All of the premolars on both sides of the mandible were removed from each dog. A POI (Ti-6Al-4V) 3-piece implant (3.7 mm in diameter and 8.0 mm in length) whose surface had been treated with anodic oxidation was placed into each test site by self-tapping. Daily application of CCEF (8 h/day) was initiated on the day following the surgery and was continued through the day of sacrifice. A CCEF was induced by an external source delivering 10-Vp-p, 60-kHz sine-wave signals through an oral electrode plate. One side of the mandible of each dog was treated with CCEF, while the other side was not. On the control side, an oral electrode plate was attached for 8 hours per day, but CCEF was not applied. The effect of daily application of CCEF on the ingrowth of bone into the implant was examined at 14, 21, or 30 days after implant placement. A fourth control group was not treated with CCEF and was maintained for 90 days to confirm that CCEF treatment enhances bone ingrowth in dental implants. RESULTS: Daily application of CCEF significantly increased the bone-contact ratio at days 14, 21, and 30 after implant placement in comparison with the respective controls. The bone-area ratios of the 14- and 21-day CCEF-treated groups were significantly larger than those of the respective controls and were similar to those of the 90-day control group. CONCLUSION: CCEF treatment increases periimplant osteogenesis in the dog mandible, confirming its usefulness in oral implantology.
Expeditious postoperative appositional growth of bone to dental implants is desired for clinically successful fixation of oral implants. The present study was performed to evaluate the effect of applying a capacitively coupled electric field (CCEF) followed by functional loading on peri-implant osteogenesis in the dog mandible. Nine adult beagles were used in this study. All premolars on both sides of the mandible were removed from each dog. A physio-odontlam implant (POI, Ti-6AI-4v) with 2 stages (3.7 mm in diameter and 8.0 mm in length), whose surface had been treated with anodic oxidation and sandblasted, was placed into each test site by self-tapping. Daily application of CCEF (8 hours per day) was initiated on the day following surgery and continued for 14 days or 21 days. After CCEF treatment was finished for each period, a prosthetic abutment and a straight post were placed on each implant. Four days after placement of the post, implants were placed under functional loading for 30 days. The dogs were then sacrificed, and histologic and radiographic studies of the mandible were performed. Relatively well calcified, mature bone with a lamellar-like structure was observed by contact microradiography and histologic study (double staining with basic fuchsin-methylene blue) of the peri-implant region on the CCEF-treated samples. In contrast, poorly calcified, immature bone without a lamellar structure was observed in control sites not treated with CCEF. The bone area ratios of the CCEF-treated sides were larger than those of control sides. These results suggest that the application of CCEF after implant placement may enhance peri-implant osteogenesis, even with functional loading.
BACKGROUND/AIMS: The survival time of patients with unresectable malignant biliary stenosis and the patent period of metallic biliary stents are different in each disease. The efficacy of the covered metallic stent was analyzed according to the primary disease. METHODOLOGY: Seventy-three patients with bile duct carcinoma (12 cases), gallbladder carcinoma (22 cases), and pancreas carcinoma (39 cases) were retrospectively enrolled. Covered metallic stents were used in 42 patients and uncovered metallic stents in 31 patients. The patency of covered stents was compared with that of uncovered stents for each disease. RESULTS: The patent rate at 6 months after insertion was 80.6% (95% CI [72.6%, 88.6%]) for the covered stent, and 49.5% (95% CI [37.6%, 61.4%]) for the uncovered stent. The mean patent periods of the covered stent and the uncovered stent were 14.6 and 27.6 months for bile duct carcinoma (p=0.424), 12.7 and 3.0 months for gallbladder carcinoma (p=0.003), and 11.9 and 9.6 months for pancreas carcinoma (p=0.919), respectively. CONCLUSIONS: The covered metallic stent was the most effective in patients with gallbladder carcinoma.
The Tyr-Pro-Phe peptide sequence, an N-terminal tripeptide fragment of opioid peptide morphiceptin, was searched on the database SEQDB (Peptide Institute, Osaka). More than 30 proteins were drawn in a list with 15 amino acid varieties at the position adjacent to Phe. Seven morphiceptin-like peptides with the H-Tyr-Pro-Phe-Xxx-NH2 sequence, where Xxx denotes the selected amino acids (Ala, Asp, Gly, Gln, Lys, Thr and Tyr), have been synthesized. Together with the side-chain protected analogs [Asp(OBzl), Lys(Z), and Thr(Bzl)], they have been evaluated for opioid activities. For the mu opioid receptors to which morphiceptin binds specifically and selectively, analogs with Xxx = Asp, Lys, Ala, Thr, Gln, Tyr and Gly showed a considerably weaker binding affinity than morphiceptin. In contrast, the Thr(Bzl) derivative demonstrated an affinity ten times greater than morphiceptin. Because of an extremely weak affinity for the delta receptors, its mu-selectivity became very high (260-fold). The present results and the increased activity of [Val4]morphiceptin (Sakaguchi et al., 36) indicate that the mu receptors tolerate the hydrophobic or aromatic residue at the site corresponding to position 4 of morphiceptin. When the circular dichroism (CD) spectra are compared between active and inactive analogs, no significant difference is found in both water and methanol. This suggests that the activity of morphiceptin analogs with the Tyr-Pro-Phe sequence is mainly determined by the structural characters of the amino acid residue in position 4 rather than by the molecular conformation. The results suggested a possible formation of morphiceptin-like peptides in various protein digests.
Dimeric analogs of neurokinin A and neurokinin B COOH-terminal heptapeptides were synthesized in order to examine the effect of ligand dimerization on the receptor selection. Dimerization was carried out at the NH2-terminus of peptides with succinic acid, yielding succinyl bis[Asp-Ser-Phe-Val-Gly-Leu-Met-NH2] (D-NKA4-10) and succinyl bis[Asp-Phe-Phe-Val-Gly-Leu-Met-NH2] (D-NKB4-10). In the assay using rat vas deferens (RVD), it was found that the deletion of the NH2-terminal tripeptide from native neurokinin A or B enhances the activity 1.5- to 8-fold, resulting in formation of NK-2 receptor specific ligands NKA4-10 and NKB4-10. When dimeric analogs of these shortened peptides, namely D-NKA4-10 and D-NKB4-10, were examined in RVD and guinea pig ileum (GPI), they were fairly potent in GPI, but not in RVD. Under conditions in which the NK-1 receptors in GPI were desensitized with NK-1 specific substance P methyl ester, dimers reduced the activity drastically, while the corresponding monomers exhibited unchanged activity. These results suggest that dimerization of the COOH-terminal heptapeptide of neurokinins changes the receptor selection of peptides from NK-2 to NK-1, and that the NK-1 receptor has a structure favorable to a dimeric peptide ligand.
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The effects of dietary salt on circulating levels of 1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine (C16 PAF) in patients with essential hypertension were studied by gas chromatography/mass spectrometry with negative ion chemical ionization. Circulating levels of C16 PAF in patients with essential hypertension (18.1 +/- 5.3 pg/ml, n = 16) were not changed compared with those in normotensive subjects (17.2 +/- 7.2 pg/ml, n = 14). Although changes in circulating levels of C16 PAF were small with changes in dietary salt, net changes in circulating C16 PAF levels significantly and positively correlated with net changes in mean arterial blood pressure (r = 0.47, P less than 0.05). Changes in C16 PAF levels also correlated with changes in creatinine clearance (r = 0.55, P less than 0.05). However, changes in C16 PAF levels did not correlate with changes in plasma sodium concentration, plasma chloride concentration and plasma volume. These results indicate that C16 PAF plays an antihypertensive role and this may be reflected as small changes in circulating levels of C16 PAF.
A family with hypercalcemia in four members is reported. The proband, a newborn girl presenting with inadequate sucking due to muscle hypotonia, marked thoracic deformity due to decalcification, hypercalcemia, and hypophosphatemia, suffers from cerebral damage due to hypoxia despite successful total parathyroidectomy of four hyperplastic glands and replacement therapy. Her 31-year-old father showed CCa/Ccr of 0.0094, normal serum Mg, hypercalcemia, hypophosphatemia and normal renal concentrating ability without kidney stone and bone abnormality. Subtotal parathyroidectomy caused only a transient fall of serum Ca. His half sister and her daughter also had symptomless hypercalcemia. Recognition of familial hypocalciuric hypercalcemia is important to avoid unnecessary parathyroid surgery and to respond effectively to severe neonatal primary hyperparathyroidism occasionally seen in such kindred.