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Biomedical subjects

Y Uchida

Publications and source records attributed to Y Uchida.

At least 109 records · Page 6Linked to original sources

Effects of ageing on proliferative ability, and the expressions of secreted protein, acidic and rich in cysteine (SPARC) and osteoprotegerin (osteoclastogenesis inhibitory factor) in cultures of human periodontal ligament cells.

Secreted protein, acidic and rich in cysteine (SPARC) has been suggested to play an important role in wound repair and mineralization. Osteoprotegerin/osteoclastogenesis inhibitory factor (OPG/OCIF) is a secreted protein that inhibits the maturation, activity and survival of osteoclasts. An examination of the changes in expression of these proteins as well as their proliferative ability according to ageing in cultured cells may elucidate characteristic changes in periodontal tissues induced by ageing. In the present study, proliferative ability and the expression of SPARC and OPG/OCIF were compared between cultures of human periodontal ligament (HPL) cells obtained from young and senior donors (in vivo cellular ageing) as well as in cultures of HPL cells at early and late passages (in vitro cellular ageing). Cumulative population doubling levels and cell population doubling time of HPL cells from young donors were greater and shorter, respectively, than those of HPL cells from senior donors. Levels of SPARC mRNA in HPL cells increased with cellular ageing in vivo. No change in the levels of OPG/OCIF mRNA in HPL cells with cellular ageing in vivo was observed. The changes in proliferative ability and the mRNA levels of SPARC and OPG/OCIF with cellular ageing in vitro were similar to those with ageing in vivo. This study demonstrated for the first time a relationship between in vivo and in vitro cellular ageing in the functional changes in HPL cells. These findings suggest that the impairment of periodontal ligament repair with ageing is due to the decrease in proliferative ability in HPL cells with ageing. Furthermore, the increase in SPARC with ageing may be related to changes in metabolism of periodontal ligament that occur with ageing.

Adult↗

An overexpression of fibroblast growth factor (FGF) and FGF receptor 4 in a severe clinical phenotype of facioscapulohumeral muscular dystrophy.

We evaluated the expression of a select panel of growth factors and their receptors, including fibroblast growth factor 1 (FGF-1), fibroblast growth factor 2 (FGF-2), platelet-derived growth factor (PDGF), FGF receptor 1 (FGF-R1), FGF receptor 3 (FGF-R3), FGF receptor 4 (FGF-R4), PDGF receptor alpha (PDGF-Ralpha), PDGF receptor beta (PDGF-Rbeta), and heparan sulfate proteoglycan (HSPG), in muscle biopsy specimens from nine facioscapulohumeral muscular dystrophy (FSHD) patients using immunohistochemistry. Two cases of Duchenne-type muscular dystrophy (DMD), two of Becker-type muscular dystrophy (BMD), and one of limb-girdle-type muscular dystrophy (LGMD) were also investigated. Widespread immunostaining for FGF-1 and FGF-2 on the sarcolemma and overexpression of FGF-R4 in endomysial and perimysial connective tissue were seen in one patient with a severe clinical phenotype of FSHD who had respiratory failure. Standard histochemistry in this patient revealed marked interstitial fibrosis and lobulated fibers. The overexpression of FGF and FGF-R4 in this severe FSHD case may be associated with the muscle fibrosis and disease severity.

Adolescent↗

Sandwich ELISA for the measurement of Apo-E4 levels in serum and the estimation of the allelic status of Apo-E4 isoforms.

Apolipoprotein-E (Apo-E) isoforms, especially theApo-E4 isoform, are considered to be genetic risk factors for familial as well as sporadic Alzheimer's disease (AD). Using monoclonal antibodies specific for Apo-E4 (MAb412-1-7) and Apo-E (LZ18), we established a sandwich ELISA for the measurement of Apo-E4 levels in serum. Total Apo-E also was determined by sandwich ELISA with a second pair of monoclonal antibodies, LZ12 and LZ18. Estimation of a patient's homozygous or heterozygous status for the Apo-E4 isoform was subsequently calculated as the ratio of Apo-E4/total Apo-E, respectively. Although the antibody for Apo-E used here does not have equivalent reactivity toward Apo-E2, -E3, or -E4, we were able to attain a fairly reliable assay system to estimate the status of the Apo-E4 isoform through a simple formula for the calculation of total Apo-E versus Apo-E4 isoform.

Alleles↗

Usefulness of magnetic resonance imaging for diagnosing deep anorectal abscesses.

PURPOSE: We evaluated the usefulness of magnetic resonance imaging for the preoperative diagnosis of deep anorectal abscesses. METHODS: Subjects were 21 patients with deep anorectal abscesses. Deep anorectal abscesses were classified into two types, ischiorectal and pelvirectal, according to their location. Patients were also classified into a single abscess group, which showed either an ischiorectal or pelvirectal abscess, and a double abscess group, which showed both ischiorectal and pelvirectal abscesses. The final diagnosis was made from surgical findings, and the types of deep anorectal abscesses determined by digital examination and magnetic resonance imaging were compared. RESULTS: Sensitivity of ischiorectal abscesses (20 lesions) with digital examination and magnetic resonance imaging was 75 and 95 percent, respectively, and that of pelvirectal abscesses (10 lesions) with digital examination and magnetic resonance imaging was 60 and 70 percent, respectively. Sensitivity of the magnetic resonance imaging was significantly higher than that of digital examination in ischiorectal abscesses. Diagnostic accuracy of digital examination and magnetic resonance imaging were both 83 percent in the single abscess group (12 patients), whereas in the double abscess group (9 patients) it was 22 and 78 percent, respectively. The rate of accurate diagnosis of magnetic resonance imaging compared with digital examination in the double abscess group was significantly higher than that in the single abscess group. CONCLUSION: Magnetic resonance imaging was useful for diagnosing and differentiating ischiorectal and pelvirectal abscesses.

Abscess↗

Surgery for ductal carcinoma in situ.

BACKGROUND: Ductal carcinomas in situ (DCIS) are sometimes treated too aggressively by surgery. We discuss minimal invasive surgery for DCIS on the basis of our experience at the Cancer Institute Hospital in Tokyo. METHODS: We performed surgery for 667 cases of DCIS between 1987 to 1998. This twelve year period we divided into three periods; 1987-1990,1991-1994, and 1995-1998. RESULTS: DCIS comprised 10% of all breast cancers, and tended to increase in incidence over time. The number of minimally invasive procedures such as breast conserving treatment (BCT), surgery without axillary dissection, and day surgery increased in later periods. In BCT for DCIS the surgical margin status is the most important factor, the rate of negative surgical margins was higher in DCIS than invasive cancer, and especially high in cases of mammographically detected nonpalpable cancer, the incidence of which is increasing yearly. The outcome of the 667 cases was very good. No distant metastases were observed, and the incidence of ipsilateral breast cancer(including second primary cancer) in these cases was 5% CONCLUSIONS: Because small cancers, including nonpalpable cases, will be detected more frequently, minimal invasive surgery will become more common for DCIS.

Axilla↗

Relationship between striatal [123I]beta-CIT binding and four major clinical signs in Parkinson's disease.

We investigated the correlation between clinical severity and striatal [123I]-CIT binding in 12 patients with Parkinson's Disease (PD: 6 men and 6 women, age: 65 +/- 7 years, Hoehn & Yahr stage: 1 to 3). The clinical severity of PD patients was measured with the Unified Parkinson's Disease Rating Scale (UPDRS) after withdrawal of antiparkinsonian medication at least 12 hours before assessment. [123I]beta-CIT binding in the caudate and putamen was measured at 3 hours [V''3 (day 1)], and at 24 hours [V''3 (day 2)) after tracer injection with small square ROIs. The specific striatal uptake index (day 2) was calculated with large square ROIs that encompassed the whole striatum. The best correlation (r = -0.82, p < 0.0012) was between putamenal V''3 (day 2) and the motor UPDRS scores. When the motor UPDRS scores were divided into four subscales, bradykinesia was the only sign that correlated significantly with putamenal V''3 (day 2) (r = -0.81, p < 0.002). [123I]beta-CIT SPECT is a useful marker of disease severity in PD with potential utility in the serial monitoring of disease progression.

Aged↗

Microvascular endothelial abnormality in skeletal muscle from a patient with gastric cancer without dermatomyositis.

We found a microvascular endothelial abnormality in a biopsy specimen from the gastrocnemius muscle of a patient with gastric cancer, who had severe myalgia and angialgia in the calf region with the symptoms of thrombophlebitis. There were no definite findings of inflammatory myopathy in histochemical and immunohistochemical studies. Electron microscopic examination revealed the accumulation of abnormal mitochondria in the subsarcolemmal area, and a fair number of degenerating capillaries. Immunohistochemical analysis of procoagulant or anticoagulant factors revealed marked reduction of thrombomodulin (TM) expression on small vessels and capillaries. Although a reduction of TM on small vessels has been observed around perifascicular atrophic fibers in patients with dermatomyositis, histochemical findings of the present patient showed no perifascicular atrophy or severely degenerating fibers. These pathological findings in the patient may be related to a malignant neoplasm and may be one of the causes of disseminated intravascular coagulation (DIC), which is the main complication of malignant neoplasms. Further studies are necessary to determine whether the reduction of TM on the small vessels and capillaries in skeletal muscle is a predictor of some severe condition such as DIC or a rare pathological finding in some special condition such as scirrhous carcinoma with thrombophlebitis.

Biopsy↗

Ebselen decreases ozone-induced pulmonary inflammation in rats.

We studied the effects of ebselen on rat lung inflammatory responses against ozone exposure. Rats were treated with ebselen every 12 h from 1 h before a single 4-h exposure to 2 ppm ozone. Treatment with ebselen (10 mg/kg) significantly decreased pulmonary inflammation as indicated by the albumin concentration and the number of neutrophils in the bronchoalveolar lavage fluid 18 h after the ozone exposure. Although treatment with ebselen did not alter the macrophage expression of inducible nitric oxide synthase after the ozone exposure, it did markedly inhibit the nitration reaction of tyrosine residues, suggesting that ebselen scavenges peroxynitrite during ozone-induced pulmonary inflammation. Treatment with ebselen also enhanced the pulmonary expression of both copper, zinc, and manganous superoxide dismutases at the same time point. These enzymes may also contribute to a decrease in the formation of peroxynitrite by lowering the concentration of superoxide. Thus, ebselen represents a useful compound for protecting against certain acute lung injuries by modulating the oxidant-related inflammatory process.

Acute Disease↗

Metastatic gastrinoma to the liver 20 years after primary resection.

Gastrinoma is a rare endocrine tumor that is frequently associated with liver metastasis. The liver metastasis is usually seen simultaneously or soon after a primary operation. A 47-year-old woman who had had a total gastrectomy 20 years earlier developed liver metastasis. An interval of this length between surgery and metastasis is extremely rare. The total gastrectomy prevented the patient from developing the usual symptoms of hypergastrinemia that would have enabled early diagnosis of the metastasis. Laboratory examinations on admission revealed a high serum gastrin concentration (1500 pg/ml). Computed tomography showed an irregularly enhanced mass lesion with an uneven, low-density central area in the right anterior inferior segment of the liver. An extended right hepatectomy was performed. Intraoperative ultrasonography showed no abnormalities in the remnant pancreas. Examination of the cut surface of the specimen revealed a yellow, firm, elastic tumor, 55 mm in diameter. The interior of the tumor appeared necrotic. Histopathologically, the tumor was composed of cells with hyperchromatic, dysplastic nuclei arranged in a trabecular pattern with nest formation. Gastrin staining was positive. A histologic diagnosis of metastatic gastrinoma was made. The patient's gastrin concentration returned to normal and she was well at 2-year follow-up.

Female↗

Injury to the gastric mucosa and cellular dynamics in a rat model of duodenogastric reflux: the possible significance of gastrin induction and a heat shock protein.

Injury to the gastric mucosa caused by duodenogastric reflux (DGR) is often encountered after gastrectomy or truncal vagotomy (V) with pyloroplasty. This study was designed to investigate the histological features of the gastric mucosa under such conditions. A rat model of DGR and DGR+V was established and the thickness of the oxyntic mucosa was measured. Cellular dynamics in the presence of injury to the gastric mucosa caused by DGR were investigated by the immunohistochemical staining of bromodeoxyuridine (BrdU) and heat shock protein 70 (HSP70). The relationship between persistent hypergastrinemia and mucosal injury was also studied. Duodenogastric reflux activated the intracellular induction of HSP70 in our rat model of DGR. Hypergastrinemia was noted in the V group. Compared with values from the DGR group, the numbers of BrdU-labeled cells increased, the glandular proliferation zone expanded, and the thickness of the oxyntic mucosa was significantly higher in the DGR+V group. Compared with the DGR group, there was greater induction of HSP in the DGR+V group during the acute stage. This finding suggests that denervation of the gastric mucosa and hypergastrinemia after vagotomy may be associated with the expression of HSP.

Animals↗

Development of an inveterate gastroduodenal ulcer caused by antral G-cell hyperplasia of the stomach (pseudo-Zollinger-Ellison Syndrome): report of a case.

We describe herein the case of a 54-year-old Japanese woman in whom an inveterate peptic ulcer developed in association with pseudo-Zollinger-Ellison Syndrome (pseudo-ZES). The patient presented with weight loss and abdominal distension caused by antral and duodenal stenosis due to an inveterate peptic ulcer. Her serum gastrin level was very high; however, no evidence of a gastrinoma or carcinoid tumor was detected by preoperative examinations or surgery. A total gastrectomy and double-tract reconstruction was performed, and pathological examination revealed a gastric ulcer (UL-IV) with no histopathological evidence of a neoplasm. Immunohistochemical staining showed an obvious increase in the number of endocrine cells that were positive for chromogranin A, and marked G-cell hyperplasia was observed in the antral mucosa. Furthermore, the number of enterochromaffin-like cells was remarkably high. From the results of the immunohistochemical examination, the patient was diagnosed as having hypergastrinemia due to antral G-cell hyperplasia. Postoperatively, the patient's serum gastrin level fell rapidly to within the normal range, her nutritional status improved, and her weight increased by about 10 kg within 1 year.

Diagnosis, Differential↗

Mechanism of quinolone resistance in Staphylococcus aureus.

The resistance mechanisms to fluoroquinolones in Staphylococcus aureus were clarified by analyzing mutations in the genes encoding target enzymes, and examining the expression of the efflux pump, and determining the inhibitory activities of fluoroquinolones against the altered enzymes. Mutations in the grlA and gyrA genes of 344 clinical strains of S. aureus isolated in 1994 in Japan were identified by combinations of methods - single-strand conformation polymorphism analysis, restriction fragment length analysis, and direct sequencing - to identify possible relationships with fluoroquinolone resistance. Five types of single-point mutations and four types of double mutations were observed in the grlA gene in 204 strains (59.3%). Four types of single-point mutations and four types of double mutations were found in the gyrA gene in 188 strains (54.7%). Among these mutations, the grlA mutation of TCC --> TTC or TAC (Ser-80 --> Phe or Tyr) and the gyrA mutation of TCA --> TTA (Ser-84 --> Leu) were the principal ones, being detected in 137 (39.8%) and 121 (35.2%) isolates, respectively. A total of 15 types of mutation combinations within both genes were related to ciprofloxacin resistance (MIC greater than or equal 3.13 microg/ml) and were present in 193 mutants (56.1%). Strains containing mutations in both genes were highly resistant to ciprofloxacin (MIC50 =50 microg/ml). Those strains with the Ser-80 --> Phe or Tyr alteration in grlA, but wild type in gyrA showed a lower level of ciprofloxacin resistance (MIC50 less than or equal 12.5 microg/ml). Levofloxacin was active against 68 of 193 isolates (35.2%) with mutations at codon 80 of grlA in the presence or absence of concomitant mutations at codons 73, 84, or 88 in gyrA (MIC less than or equal 6.25 microg/ml). Sitafloxacin (DU-6859a) showed good activity in 186 of 193 isolates (96.4%), with an MIC of less than or equal 6.25 microg/ml. The contribution of membrane-associated multidrug efflux protein (NorA) expression to fluoroquinolone resistance was clarified by the checker-board titration method for determining the MIC of norfloxacin alone and in combination with carbonyl cyanide m-chlorophenylhydrazone. Among 344 clinical isolates, 139 strains (40.4%), in which the MIC of norfloxacin varied from 1.56 to >800 microg/ml, overexpressed the NorA protein. GrlA and GrlB proteins of topoisomerase IV, and GyrA and GyrB proteins of DNA gyrase encoded by genes with or without mutations were purified separately. The inhibitory activities of fluoroquinolones against the topoisomerase IV which contained a single amino acid change (Ser --> Phe at codon 80, Glu --> Lys at codon 84 of grlA, and Asp --> Asn at codon 432 of grlB) were from 5 to 95 times weaker than the inhibitory activities against the non-altered enzyme. These results suggest that the mutations in the corresponding genes may confer quinolone resistance; the active efflux pump, NorA, was considered to be the third quinolone-resistance mechanism. The numerous and complicated mutations seen may explain the rapid and widespread development of quinolone resistance described in S. aureus. Sitafloxacin showed good antibacterial activity against ciprofloxacin- or levofloxacin-resistant mutants because of its high inhibitory activity against both topoisomerase IV and DNA gyrase.

DNA Topoisomerase IV↗

Endoscopic injection sclerotherapy for esophageal varices prolonged survival of patients with hepatocellular carcinoma complicating liver cirrhosis.

BACKGROUND: A prospective controlled study was performed between 1982 and 1991 to evaluate the efficacy of endoscopic injection sclerotherapy (EIS) in patients with esophageal varices complicated by hepatocellular carcinoma and liver cirrhosis. METHODS: The study included 83 patients with esophageal varices, hepatocellular carcinoma, and liver cirrhosis. Forty-three patients (group 1) underwent prophylactic EIS or emergent EIS for bleeding varices. EIS was performed weekly 4 to 6 times until the varices disappeared. The remaining 40 patients (group 2) underwent conservative therapy and did not undergo EIS. Survival rates were compared between the 2 groups. RESULTS: During the 5-year observational period, all patients who did not undergo EIS died. Sixteen in group 2 (40.0%) died of gastrointestinal bleeding including ruptured esophageal varices. In contrast, patients treated with EIS survived significantly longer (p<0.001). Nine patients (20.9%) treated with EIS experienced gastrointestinal bleeding as a result of which 5 (11.6%) died. EIS prolonged survival in patients classified as Child's A or B but did not affect survival in patients with Child's C hepatic function. EIS was effective in prolonging survival in patients with hepatocellular carcinomas smaller than 5 cm. However, EIS had no effect in patients with hepatocellular carcinomas that were larger than 5 cm. EIS prolonged survival only for patients with nodular hepatocellular carcinoma and had no effect in patients with massive and diffuse hepatocellular carcinoma. Further, EIS prolonged survival only for patients who did not have portal vein thrombosis. CONCLUSION: Based on this prospective study, we concluded that EIS was effective in prolonging the survival period of a select subset of patients with hepatocellular carcinoma.

Aged↗