Efficacy of endothelin-1 receptor antagonist for protecting the function of grafted livers from preservation-reperfusion injury in pigs.
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Biomedical subjects
Publications and source records attributed to H Ohkubo.
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BACKGROUND/AIMS: Interferon therapy has a beneficial effect in patients with chronic hepatitis C who have a low viral load. The aim of this study was to compare the core protein level with HCV RNA levels and to analyze whether virus quantitation predicts the efficacy of interferon therapy. METHODS: HCV core protein level assessed by the recently developed assay was compared with HCV RNA levels measured by three different methods (Amplicor-HCV monitor, competitive RT(CRT)-PCR, and bDNA probe assay) in 352 patients with chronic hepatitis C in relation to viral serotype. RESULTS: From 91% (320/352) to 93% (299/322) of patients with viremia were detected by Amplicor-monitor and CRT-PCR, in contrast to 60% (187/312) and 74% (191/258) by bDNA and HCV core protein assay, respectively. The HCV core protein level was positively correlated with HCV RNA levels measured by the three assays (r = 0.680 to 0.731). Serum HCV RNA and core protein levels were significantly lower in patients with serotype 2 than in those with serotype 1. Viral eradication after interferon therapy was observed in 60-70% of the patients with < 1 x 10(4) copies/ml of HCV RNA by Amplicor-monitor assay, < 2 x 10(5) copies/ml by CRT-PCR, < 0.5 Meq/ml by bDNA assay, and < 20 pg/ml of core protein by HCV core protein assay. Viral eradication was uncommon (< 11%) among the patients with higher viral loads. Bivariate analysis revealed that the outcome of interferon therapy was more closely associated with both HCV core protein and RNA levels than the HCV serotype. CONCLUSIONS: Quantitation of HCV core protein and HCV RNA in useful for prediction of the interferon response.
The purpose of this study was to establish a new technique for distraction osteogenesis in the maxilla, using an osseointegrated implant and intraoral device. After extraction of the premolar and molar teeth, four titanium implants were installed in the maxillary alveolar bone. Three months later, the distraction device was connected to the abutments, and osteotomy in the medial portion of maxilla between the implants was performed. Distraction was carried out at the rate of 1 mm per day to obtain a 10-mm elongation, Morphological, radiographic and histological examinations showed that successful maxillary advancement was achieved. New bone was primarily formed by intramembranous ossification and partial endochondral ossification. Titanium implants placed for anchorage of the distraction device remained stable during the course of maxillary advancement. This technique can provide significant advancement of the maxilla with better stability. The treatment system can be applied in any kind of maxillary deformities which need to be corrected surgically by classic osteotomy without bone grafting.
A cylindrical incision was made in the calvarial bone of mongrel dogs. Using a distraction device that used bone-connecting implants as supports, vertical distraction osteogenesis of calvarial bone was performed. Calvarial bone was distracted vertically at a speed of 0.5 mm per day, making enlargement of the cranium possible. The gap that resulted from distraction was closed with newly formed bone. The implants made a solid connection with no oscillation or dislodgment from the external pressure used for distraction. Our results show that vertical distraction of thin calvarial bone can be done using osseointegrated implants as supports. This indicates the possibility of broadening the applications of this method to plastic correction of craniomaxillofacial bone.
We report a 45-year-old male with chronic myelogenous leukemia (CML) who experienced skin ulcers of the left lateral malleolus and dorsum of both feet. He had been treated with hydroxyurea (HU) for 2 years. His leg ulcers improved after HU was discontinued. Skin biopsy of the ulcerated lesion revealed that the lesion is compatible with small vessel vasculitis, but circulating immune complexes (C1q, anti-C3d antibody) were negative. Although the precise mechanism of the skin ulcer is unknown, we must take into consideration the skin changes were secondary to hydroxyurea therapy in myeloproliferative disorders.
We cloned two novel types of TEA domain-containing transcription factor (ETFR-1 and -2) cDNAs. Amino acid sequences deduced for ETFR-1 and -2 as well as those of other known proteins of the same family, TEF-1 and ETF, exhibited significant identity (63-75% overall) to each other not only in the TEA DNA binding domain but also in the C-terminal regions. Northern blot analysis revealed that both the mRNAs were expressed in embryos as well as in many adult tissues, although their levels of expression varied. The results demonstrate that the mammalian TEA domain-containing transcription factor family consists of at least four distinct members, TEF-1, ETF, ETFR-1, and ETFR-2, which exhibit overlapping but differing spatiotemporal expression patterns, suggesting their redundant yet unique roles involved in not only developmental control but also tissue-specific regulation.
P19 mouse embryonal carcinoma cells differentiate into neurons and glial cells when treated with retinoic acid. In contrast, a subline of the P19 cells, RAC65, is known to show little sign of differentiation with the treatment. We treated the two embryonal carcinoma (EC) cell lines with 9-cis-retinoic acid and investigated its neuron-inducing activity. In P19 cells, 9-cis-retinoic acid showed an activity equal to that of all-trans-retinoic acid. However in RAC65 cells, 9-cis-retinoic acid induced neurons 10-fold more effectively than all-trans-retinoic acid. The order in which various retinoids appeared in P19 cells corresponded to that of retinoic acid receptors, and the order in RAC65 cells to that of retinoid X receptors (RXRs). Furthermore we found that the down-regulation of retinoid X receptor-gamma mRNA expression was associated with neuronal differentiation in both embryonal carcinoma cell lines. In addition, a synthetic RXR-selective retinoid induced neurons from both EC cells. Our findings support an intriguing possibility that the 9-cis-retinoic acid/retinoid X receptor system may play an important role in neural differentiation.
Embryonic TEA domain-containing factor (ETF) belongs to the family of proteins structurally related to transcriptional enhancer factor-1 (TEF-1) and is implicated in neural development. Isolation and characterization of the cosmid clones encoding the mouse ETF gene (Etdf) revealed that Etdf spans approximately 17.9 kb and consists of 12 exons. The exon-intron structure of Etdf closely resembles that of the Drosophila scalloped gene, indicating that these genes may have evolved from a common ancestor. The multiple transcription initiation sites revealed by S1 protection and primer extension analyses are consistent with the absence of the canonical TATA and CAAT boxes in the 5'-flanking region, which contains many potential regulatory sequences, such as the E-box, N-box, Sp1 element, GATA-1 element, TAATGARAT element, and B2 short interspersed element (SINE) as well as several direct and inverted repeat sequences. The Etdf locus was assigned to the proximal region of mouse chromosome 7 using fluorescence in situ hybridization and linkage mapping analyses. These results provide the molecular basis for studying the regulation, in vivo function, and evolution of Etdf.
We cloned two rat cDNAs of brain basic helix-loop-helix factor 1 (BHF1). These have an identical coding region, contain 357 amino acids and exhibit 94.6% identity to MATH-2/NEX1 in the basic helix-loop-helix region. BHF1mRNAs are dominantly expressed in the brain particularly in the cerebellum, in the adult bovine, rat and mouse. Two shorter BHF1mRNAs (1.6 kb and 1.8 kb) were also detected in the mouse embryo, and these decreased in the developmental process. These results suggest that BHF1 may play important roles in cerebellum-specific functions and development of neurons.
We cloned a novel basic helix-loop-helix protein, NDRF (NeuroD-related factor), cDNA. NDRF contains 383 amino acids and exhibits 53.4% and 52.2% sequence identity to NeuroD and MATH-2/NEX-1, respectively. NDRF mRNA appears in the brain of 12-day-old mouse embryos and is localized in certain regions of the adult brain, such as the hippocampus, dentate gyrus and cerebellum, Thus, the structure and expression patterns of NDRF are similar to but distinct from those of NeuroD and MATH-2/NEX-1, suggesting that NDRF may play distinct roles in neural development and plasticity as a novel member of the NeuroD family.
In an attempt to prevent postoperative intraperitoneal recurrence in patients with advanced gastric cancer and consequently to improve survival time, we treated patients with intraperitoneal hyperthermic perfusion (IPHP) using mitomycin C (MMC) combined with surgery. There were 60 patients with advanced gastric cancer who were treated with IPHP (long-term study) group, and the survival of this group was compared with the outcome in 52 patients with advanced gastric cancer treated with surgery alone (control group). To avoid or diminish side effects derived from scald injury of the peritoneal surface due to IPHP, 50 mg/kg of cimetidine was given intravenously just before administration of IPHP. For prophylaxis of anastomotic leakage, duodenostomy using a Foley catheter was performed. The 60 patients who were treated with IPHP lived longer than the 52 patients in the control group (p = 0.000610). The 3 year survival rate was 45 percent for the former compared with 16 percent for the latter. The intravenous administration of cimetidine just prior to IPHP protected the peritoneoserosal surface from scald injury, even though the heated perfusate exposure was at 44.3-46.3 degrees C for 2 hours. Because the intraabdominal pressure within the duodenum and jejunum was decompressed postoperatively through catheter duodenostomy and the peritoneoserosal surface was protected from scald injury caused by IPHP, anastomotic leakage in the study group was nil. Therefore, IPHP treatment plus aggressive surgery combined with pre-IPHP cimetidine administration are indicated for patients with advanced gastric cancer. The side effects of IPHP and postoperative morbidity can thus be reduced and a favorable outcome obtained.
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PURPOSE: This study investigated an approach to distraction osteogenesis of the mandible using osseointegrated implants and an intraoral device. MATERIALS AND METHODS: Five adult dogs were used for this experiment. After the extraction of the left mandibular premolar and molar teeth, two osseointegrated implants were placed. Abutment connection, attachment of the intraoral distraction device, and an osteotomy in the region between the implants were performed 3 months after implantation. The distraction was done at rate of 1 mm/day for 10 consecutive days to elongate the mandible 10 mm. The animals were killed 2, 3, and 4 weeks after the distraction was completed, and radiographic and histologic examinations were done. RESULTS: The longer the time after completion of distraction, the more uniform the new bone that was observed radiographically and histologically in the gap created by the distraction. The titanium implants remained stable during the course of mandibular lengthening. CONCLUSION: An intraoral device using osseointegrated dental implants can serve as a mechanism for distraction osteogenesis in the maxillofacial skeleton.
Prulifloxacin (PUFX), a new quinolone antimicrobial agent, was administered to a total of 122 patients and carriers to investigate its clinical efficacy, safety and usefulness in infectious enteritis (bacillary dysentery, enteritis caused by Salmonella spp. and enteropathogenic E. coli, cholera and so on). In addition, the minimum inhibitory concentration (MIC) of UFX (active compound) was determined against each clinical isolate, and compared with that of ciprofloxacin (CPFX), ofloxacin (OFLX), tosufloxacin (TFLX) and nalidixic acid (NA). The correlation between the concentration of UFX in feces and the change of the fecal microflora were also investigated when PUFX was administered to the patients with acute infectious enteritis. A daily dose of 400 mg of PUFX was administered orally in two divided doses (morning and evening) for 5 days, with the exception of 7 days administration against salmonella enteritis and 3 days administration against cholera. 84 cases were adapted for evaluating the usefulness. The clinical efficacy was 100% in all the enteritis except salmonella enteritis, in which it was 88.9% (8/9 cases). On the bacteriological efficacy, the elimination rate was 100% in all isolates except Salmonella spp., in which it was 75.0% (12/16 cases). As for the adverse effect, uriticaria in moderate degree was observed in 1 (0.9%) of 109 cases. Abnormal changes in laboratory findings were seen in 3 (3.0%) of 100 cases, consisting of 1 with eosinophilia and 2 with elevated S-GPT, although they were all slight in degree. The usefulness rate was 65.5% (55/84 cases) for "very useful" and 95.2% (80/84 cases) for "very useful" and "useful". MIC90 of UFX against Shigella spp., Salmonella spp., E. coli and V. cholerae, was 0.025, 0.05, 0.025 and 0.05 microgram/ml, respectively. These values were the same as those of CPFX and TFLX, and superior to OFLX and NA. UFX concentrations in feces followed by administration of PUFX in 3 cases with acute infectious enteritis were higher than that of MIC90 of UFX against Shigella spp., Salmonella spp., E. coli and V. cholerae. The changes of the fecal microflora, which influence the efficacy and safety of PUFX, were not observed.
The influence of KU-1257 on the recurrence and relapse of acetic acid ulcers in rats was investigated grossly and histologically in comparison with that of cimetidine. The ulcer was induced by topical application of glacial acetic acid at the junction of the corpus and antrum on the anterior wall of the stomach. The drug was administered from the 5th to the 153rd day after the ulcer induction and then discontinued to the 238th day. The healing rates of the control groups (control) rose until the 119th day after the ulcer induction, followed by ups and downs. The quality of healing in the regenerated mucosa and the granulation tissue of the healed ulcer was poor, resulting in the recurrence and relapse of ulcers. The recurrence and relapse of ulcers also occurred in the cimetidine groups (CIM). On the other hand, the KU-1257 groups (KU-1257) showed much lower recurrence and relapse rates of ulcers than the control and CIM groups. Moreover, KU-1257, unlike CIM, improved the quality of ulcer healing throughout the period of its administration and even after it was discontinued. These results suggest that KU-1257 improves the quality of ulcer healing, and this may contribute to the low recurrence and relapse rates of ulcers.
We identified a novel cDNA related to that of transcriptional enhancer factor-1 (TEF-1) during the course of isolation and characterization of cDNAs, whose mRNAs are preferentially expressed in the mouse neural precursor cells. The putative polypeptide, termed embryonic TEA domain-containing factor (ETF), deduced from the nucleotide sequence contains 445 amino acids and shares 66% amino acid identity with mouse and human TEF-1 proteins. The primary structure of the TEA domain, a probable DNA-binding domain, and the specific DNA binding activity to the GT-IIC motif of ETF are indistinguishable from those of the known vertebrate TEF-1 proteins. However, the expression of the ETF gene is strictly regulated in developing embryos and is limited to certain tissues, such as the hindbrain of a 10-day-old mouse embryo, in contrast to the ubiquitous expression pattern of the TEF-1 gene. These results suggest that ETF is a novel mammalian member of the TEA domain-containing transcription factor family and may be involved in the gene regulation of the neural development. We have discussed the possible existence of multiple subtypes of the mammalian TEF-1 family proteins, which may play different roles in cellular and development gene regulation.
We examined cutaneous manifestations of rheumatoid arthritis (RA) of 142 Japanese patients who visited both the Departments of Dermatology and Rheumatology of our hospital. We classified cutaneous lesions into specific and/or characteristic or nonspecific ones. Nonspecific lesions predominated in our series. Among the specific skin manifestations, which comprised 10% of the total, rheumatoid nodules, rheumatoid papules, rheumatoid neutrophilic dermatitis, and severe vasculitic ulcers correlated with high titers of rheumatoid factors and progression of RA, while purpura and livedo did not. Nonspecific skin manifestations failed to correspond with the level of rheumatoid factors. Among the nonspecific lesions, asteatotic eczema, candida interdigitalis, and tinea unguium were commonly detected.
This study analyzed intraoperative indication for splenectomy at the time of total gastrectomy, based on 249 gastric cancer patients. Data on these patients were studied with special reference to the relationship between intraoperative gross findings such as serosal invasion, tumor size, histologic patterns and nodal metastasis to the splenic hilus. Fifty-three of the 249 patients (21.3%) had a positive metastasis. The incidence of nodal metastasis to the splenic hilus was high in patients with a primary lesion in the entire stomach (26/72: 36.1%). In case of no serosal invasion of the primary lesion, there was no nodal involvement to the splenic hilus (0/42). The low incidence of nodal metastasis occurred in case of a tumor size of less than 40 mm in the largest diameter (1/60: 1.7%) and with histological findings of signet ring cell carcinoma (1/19: 5.3%). Although site and size of the primary tumor, depth of tumor penetration, and histologic findings are interdependent variables, these factors indicate probable nodal involvement to the splenic hilus and unnecessary splenectomy can be avoided.