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Biomedical subjects

Y Fukuda

Publications and source records attributed to Y Fukuda.

At least 73 records · Page 4Linked to original sources

Angiotensin converting enzyme gene polymorphism in primary vesicoureteral reflux.

We studied the insertion/deletion (I/D) polymorphism of the angiotensin converting enzyme (ACE) gene in 78 patients with primary vesicoureteral reflux (VUR), and examined renal function by dimercaptosuccinate (DMSA) renoscintigraphy and diethylenetriamine-penta-acetic acid (DTPA) renogram in each genotype. Patients were classified into three genotypes according to the ACE gene I/D polymorphisms: 32 in II genotype, 36 in ID, and 10 in DD. The incidence of presumably congenital unilateral small kidneys was high in DD patients (70%). Glomerular filtration rate obtained from DTPA renogram was 120.7+/-35.7 ml/min (expressed as mean+/-SD) in II genotype, 111.7+/-33.3 in ID, and 88.0+/-18.0 in DD. The total quantitative DMSA tracer uptake of both kidneys was also low in patients with the D allele. This study shows that the D allele of ACE gene is closely related to small congenital kidneys with refluxing ureters in patients with primary VUR, and in accordance with previous reports, this allele is also related to the progression of reflux nephropathy.

Alleles↗

Human arylhydrocarbon receptor repressor (AHRR) gene: genomic structure and analysis of polymorphism in endometriosis.

The diversity of biological effects resulting from exposure to dioxin may reflect the ability of this environmental pollutant to alter gene expression by binding to the arylhydrocarbon receptor (AHR) gene and related genes. AHR function may be regulated by structural variations in AHR itself, in the AHR repressor (AHRR), in the AHR nuclear translocator (ARNT), or in AHR target molecules such as cytochrome P-4501A1 (CYP1A1) and glutathione S-transferase. Analysis of the genomic organization of AHRR revealed an open reading frame consisting of a 2094-bp mRNA encoded by ten exons. We found one novel polymorphism, a substitution of Ala by Pro at codon 185 (GCC to CCC), in exon 5 of the AHRR gene; among 108 healthy unrelated Japanese women, genotypes Ala/Ala, Ala/Pro, and Pro/Pro were represented, respectively, by 20 (18.5%), 49 (45.4%), and 39 (36.1%) individuals. We did not detect previously published polymorphisms of ARNT (D511N) or the CYP1A1 promoter (G-469A and C-459T) in our subjects, suggesting that these polymorphisms are rare in the Japanese population. No association was found between uterine endometriosis and any polymorphisms in the AHRR, AHR, ARNT, or CYP1A1 genes analyzed in the present study.

Aryl Hydrocarbon Receptor Nuclear Translocator↗

IQGAP1, a negative regulator of cell-cell adhesion, is upregulated by gene amplification at 15q26 in gastric cancer cell lines HSC39 and 40A.

Our previous comparative genomic hybridization (CGH) study revealed a novel amplified region at 15q26 in two cell lines established from diffuse types of gastric cancer (GC). In this amplified region, FES and IGF1R, known targets on 15q26, were located telomeric to the amplicon in the two cell lines, HSC39 and 40A, suggesting that another tumor-associated gene exists in this region. While screening expressed sequence tags (ESTs) for novel genes in this region, we identified the IQGAP1 amplification. IQGAP1 has been reported to encode a ras GAP-related protein, and its interaction with cadherin and/or beta-catenin induces a dissociation of beta-catenin from the cadherin-catenin complex, one of the mechanisms for cell-cell adhesion. Northern and Western blot analyses revealed that amplification of this gene was accompanied by corresponding increases in mRNA and protein expression. Moreover, immunocytochemical staining showed that overexpressed IQGAP1 accumulated at the membrane, suggesting its colocalization with beta-catenin. Taken together, these findings suggest that IQGAP1 may be one of the target genes in the 15q26 amplicon correlated with a malignant phenotype of gastric cancer cells, such as diffuse and invasive characteristics, through the disruption of E-cadherin-mediated cell-cell adhesion.

Carrier Proteins↗

Treatment of ruptured hepatocellular carcinoma.

BACKGROUND: The problem of whether surgical or conservative treatment is indicated for ruptured hepatocellular carcinoma (HCC) has not been analyzed from the viewpoint of long-term development of hepatitis viral infection from liver fibrosis to liver cirrhosis. Although transcatheter arterial embolization (TAE) for hemostasis followed by two-stage hepatectomy has been established as the best treatment for ruptured HCC, there still remain difficulties in the treatment of some patients. METHODS: Twelve patients with ruptured HCC who were surgically or conservatively treated were retrospectively analyzed in terms of modality of treatment, liver function, extension of HCC, complications, survival rate, and cause of death. RESULTS: Tumor rupture can occur either in the early phase or in the terminal phase during the development from liver fibrosis to liver cirrhosis, while tumor rupture occurs at the advanced stage in terms of HCC extension. TAE for emergent hemostasis or prevention of re-bleeding was performed in ten patients, while TAE was contraindicated in one patient and emergent laparotomy for hemostasis was performed in one patient. In four patients, elective extended surgical resection was performed, because liver function was evaluated as clinical stage 1 according to the General rules for the clinical and pathological study of primary liver cancer of the Liver Cancer Study Group of Japan. In seven patients, conservative or medical treatment was selected, because liver function was evaluated as poor. The surgically treated group, who could tolerate extensive operation, survived longer than the conservatively treated group. CONCLUSIONS: While TAE remains the best method to employ for hemostasis, it still has limitations. Hence, we should be mindful of other possible modalities for hemostasis and their outcomes. Rupture of HCC at an early phase in the development of liver fibrosis is a good indication for elective surgical treatment and should be distinguished from rupture in the terminal phase of liver cirrhosis, which should be treated conservatively. Although elective surgical treatment can be performed in selected patients, tumor size and location of HCC, in addition to liver function, should be taken into consideration.

Aged↗

A useful ELISA system for human liver-type arginase, and its utility in diagnosis of liver diseases.

OBJECTIVES: To develop a new ELISA system for liver-type arginase using monoclonal antibodies against the enzyme, and to verify the utility of the arginase in diagnosis of hepatic disorders. DESIGN AND METHODS: We have developed an enzyme-linked immunosorbent assay (ELISA), using two kinds of monoclonal antibodies (Mo6G3 and Mo9C5) for human liver-type arginase as the first and second antibodies respectively. We have also developed a new method to eliminate the influence of erythrocyte-derived arginase contamination in hemolytic samples. This ELISA was applied to specimens received from patients with acute and chronic hepatic disease and also patients who had undergone partial hepatectomy. RESULTS: This assay is sensitive and reproducible for the measurement of liver-type arginase in the sera of patients with liver dysfunction, and enabled us to detect enzyme concentrations as low as 27 pmol/L without any processing of the samples. The assay showed within-run coefficients of variation (CV) ranging from 1.9 to 4.1% and between-day CV from 3.6 to 5.1% for arginase concentrations varying from 57.1 to 1200 pmol/L. The recovery was 113% (mean) with a range of 96 to 129%. These antibodies reacted strongly with both recombinant and native liver-type arginases, while, to some extent, with erythrocyte-derived arginase. Correction for erythrocyte-derived arginase contamination in hemolytic samples was, however, easily made by assaying peroxidase-like activity of hemoglobin. From the view of a limited localization of arginase in the liver, the marked increase of the enzyme in serum reflects initiation of liver injury, while the rapid decrease reflects termination of the damage. Such quick normalization in circulating liver-type arginase indicated another merit of the enzyme in diagnosis of liver diseases. CONCLUSIONS: The changes in circulating liver-type arginase level could be helpful not only in the diagnosis of liver diseases but also subsequent treatment of the patients with liver damage.

Acute Disease↗

Normal ventilation and ventilatory responses to chemical stimuli in juvenile mutant mice deficient in endothelin-3.

Congenital central hypoventilation syndrome (CCHS) and Hirschsprung's disease (HSCR) are often classified as neurocristopathies and are thought to share a common molecular pathogenesis related to the genes that control the development of neural crest cells. We examined whether endothelin-3 (ET-3), one of the developmental regulators of neural crest cells and of which null mutation results in aganglionic megacolon in mice, fulfills the requirements for such a common molecule. To investigate the possible involvement of ET-3 in central ventilatory control, we measured ventilation in mutant mice deficient in ET-3 by whole body plethysmography. Tidal volume and breathing frequency were measured during breathing of room air, hypoxic, hyperoxic, or hypercapnic gas mixtures in awake and anesthetized mice. There were no significant differences in resting ventilation as well as ventilatory responses to hypoxia and hypercapnia between ET-3-knockout mice and wild-type mice. Our results indicate that ET-3 can not be considered as a common pathogenic mechanism for CCHS and HSCR at least in mice.

Anesthesia↗

Intraarterial low-dose cisplatin via an indwelling port and concurrent radiotherapy for invasive bladder cancer.

Thirteen patients with invasive bladder cancer who had residual tumor after transurethral resections, were treated with consecutive intraarterial (IA) cisplatin (15 mg/d; total, 150 mg) and concurrent radiation (1.8 Gy/d; total, 30.6 Gy). All patients received unilateral or bilateral placement of vascular access devices (VAD) to perform daily cisplatin infusion after alteration of intrapelvic blood flow by coil embolizations. Tumor response was evaluated by transurethral biopsy 2 weeks after treatment. Complete response, defined as no viable tumor cell in the biopsy specimen, was achieved in seven patients (54%). After a median follow-up of 30 months (range, 12-48 months), 10 patients (77%) were alive, five (38%) of whom had no recurrence. Two cancer-related deaths were observed. All complete response cases survived with a median follow-up of 35 months (range, 25-48 months). Cause-specific and disease-free survival rates at 4 years were 85% and 28%, respectively. The regimen was well-tolerated, with no dose-limiting toxic events. There were no VAD-related complications. Consecutive IA low-dose cisplatin and concurrent radiation may be an acceptable alternative treatment for patients with bladder cancer who are not suitable for systemic chemotherapy. The use of a VAD contributed to successful consecutive IA infusions.

Aged↗

Evaluation of the association between serum anti-Lewis X antibody and inflammatory infiltration into the gastric mucosa infected with Helicobacter pylori.

BACKGROUND: Lipopolysaccharides of Helicobacter pylori have an antigenic structure that mimics Lewis X occurring in gastric mucosa. The pathogenic role of antigenic mimicry in Helicobacter pylori-induced gastritis has been of recent interest. AIM: To examine whether this molecular mimicry affects gastric mucosal inflammation in patients infected with Helicobacter pylori. PATIENTS: A total of 59 patients (mean age 58.0 years, 35 males, 24 females) were studied. METHODS: Serum samples were collected to measure IgG antibodies to Helicobacter pylori and Lewis X. Biopsy specimens were obtained from the antrum and corpus for the grading of gastritis. Correlation coefficients between serum Lewis X antibody titre and histological grades of inflammatory infiltration were determined. RESULTS: There was no significant correlation between anti-Lewis X antibody titre and the grade of mononuclear or polymorphonuclear cell infiltration. High titre of anti-Lewis X antibody was seen only in patients who had increased inflammatory infiltration in the corpus. CONCLUSIONS: Serum anti-Lewis X antibody, possibly induced by Helicobacter pylori infection, does not seem to play a major role in gastric mucosal inflammation in patients with Helicobacter pylori infection.

Female↗

Ceratomyxa seriolae n. sp. and C. buri n. sp. (Myxozoa: Myxosporea) from the gall-bladder of cultured yellowtail Seriola quinqueradiata.

Ceratomyxa seriolae n. sp. and C. buri n. sp. (Myxozoa: Myxosporea) were found in the gall-bladder of cultured yellowtail Seriola quinqueradiata Temminck & Schlegel (Carangidae) in Japan. Mature spores of C. seriolae n. sp. were elongate and 6.5 (6.0-7.5) microm long and 33.7 (28.0-41.5) microm thick. Disporous plasmodia of C. seriolae n. sp., 40-100 microm in size, were amoeboid to spherical. C. buri n. sp. were elliptical with a flattened posterior end. 6.5 (5.5-7.5) microm long and 14.3 (11.0-16.5) microm thick. Spherical plasmodia of C. buri n. sp., 15-20 microm in diameter, were disporous. In periodical sampling of yellowtail bile from August, 1999 to February, 2000, the two new species of Ceratomyxa, as well as Myxobolus spirosulcatus Maeno, Sorimachi, Ogawa & Kearn 1995, first appeared in October, and the prevalences were very variable (20-100%) during the study period.

Animals↗

Pathology of the desmoplastic ameloblastoma.

Desmoplastic ameloblastoma is a rare variant of ameloblastoma and only 54 cases have been previously reported in the English literature. We report ten cases of desmoplastic ameloblastoma of the jaw observed between 1972 and 1998 and discuss the pathogenesis of the tumor. Eight of the ten tumors were located in the anterior region of the jaw. Radiographically, six cases showed mixed radiolucent/radiopaque appearance with ill-defined margins and the other four cases lacked typical findings of ameloblastomas. The tumors were located mainly in the alveolar region and occupied the tooth-bearing area, without tooth resorption or impacted teeth. Histologically, the desmoplastic ameloblastomas were characterized by extensive stromal desmoplasia, and small tumor nests of odontogenic epithelium were scattered in the stroma. Oxytalan fibers stained by potassium monopersulfate-aldehyde fuchsin were demonstrated in the stroma of all desmoplastic ameloblastomas. From these findings, we presumed that the desmoplastic ameloblastomas might have developed in the periodontal membrane.

Adolescent↗

Role of MMP-2 in alveolar epithelial cell repair after bleomycin administration in rabbits.

Matrix metalloproteinases (MMPs) have been implicated in the pathological processes of interstitial lung diseases. However, underlying mechanisms, particularly for activity levels and distribution of activated MMP-2 in the disease process, are yet to be elucidated. The present study investigated the immunolocalization of MMP-2, membrane type 1-matrix metalloproteinase (MT1-MMP), tissue inhibitor of metalloproteinase (TIMP)-2, p53, and Ki-67 in a rabbit model of bleomycin-induced pulmonary fibrosis. Gelatin zymography and in situ zymography were used to examine the activity and the localization of MMP-2. Furthermore, we performed Western blot and in situ hybridization for MT1-MMP, an activator for MMP-2. The total MMP-2 level estimated by gelatin zymography increased significantly at 3, 7, and 14 days after bleomycin administration, compared with controls. In the immunohistochemical study, immunoreaction for MMP-2 was strongest in alveolar epithelial cells among the cell populations. Swollen and/or elongated type II alveolar epithelial cells showed strong immunoreactions for MMP-2, MT1-MMP, and TIMP-2. After bleomycin administration, immunoreaction for p53 was observed in bronchiolar and alveolar epithelial cells. The proportion of p53-positive cells was high in epithelial cells from 1 to 14 days as MMP-2 levels were increased, suggesting that p53 may be responsible, at least in part, for the increase of MMP-2. The ratio of activated MMP-2 to total MMP-2 estimated by gelatin zymography increased significantly at 3, 7, 14, and 28 days after bleomycin treatment. In situ zymography revealed that type II alveolar epithelial cells degraded gelatin. An increased expression of MT1-MMP protein was observed by Western blot following administration of bleomycin. In situ hybridization demonstrated that type II alveolar epithelial cells gave intense signal for MT1-MMP mRNA. These results suggest that type II alveolar epithelial cells express MT1-MMP and activate MMP-2 on their cell surfaces, which may lead to the elongation and migration of alveolar epithelial cells in the repair process of bleomycin-induced pulmonary fibrosis.

Animals↗

Safety and complications of interventional radiology for hepatocellular carcinoma in patients with haemophilia and cirrhosis.

Many patients with haemophilia have been chronically infected with hepatitis virus owing to multiple transfusions and the prevalence of hepatocellular carcinoma will probably increase in this population. We evaluated the safety and complications of radiological intervention for hepatocellular carcinoma in eight patients with haemophilia and cirrhosis. Radiological interventions can be performed safely in all patients with haemophilia. Unexpectedly, the most common complication was bleeding from the gastrointestinal tract. Attention should be paid to this potential problem in order to take appropriate steps to minimize its occurrence.

Adult↗

Effects of HAART on hepatitis C, hepatitis G, and TT virus in multiply coinfected HIV-positive patients with haemophilia.

In multiply coinfected human immunodeficiency virus (HIV)-positive patients, we investigated the effects of high-activity antiretroviral therapy (HAART) using HIV protease inhibitors on three other viruses: hepatitis C virus (HCV), hepatitis G virus (HGV), and TT virus (TTV). Viral concentrations were measured serially by polymerase chain reaction methods in five patients with quadruple infection (HIV, HCV, HGV, and TTV) and in two patients with triple infection (HIV, HCV, and HGV) before and during HAART. In addition, CD4+ cell counts and serum alanine aminotransferase (ALT) levels were measured serially. Generally we observed no difference in serum HCV RNA, HGV RNA, or TTV DNA concentrations between samples obtained before and after initiation of HAART, whereas HIV RNA concentration decreased and CD4 counts increased in most patients. However, two patients had markedly decreased concentrations of HCV RNA and HGV RNA, respectively, more than 12 months after beginning HAART. Normalization of serum ALT levels was observed in a patient with decline of HCV RNA concentrations. No interactions were observed among these four viruses. HAART had no apparent direct effects on HCV, HGV, or TTV. Further studies will be required to elucidate whether the restoration of immune status through suppression of HIV replication by HAART may affect HCV or HGV RNA concentrations.

AIDS-Related Opportunistic Infections↗

Case report. First isolation of Trichosporon domesticum from a cat.

The present study deals with the first isolation of Trichosporon domesticum from the urine of a cat with chronic cystitis. A 5-year-old domestic short hair cat weighing 5.6 kg was referred to an animal hospital with the chief complaint of haematuria having persisted for 3 weeks. The isolate was identified as T. domesticum, confirming the result of mycological examination by molecular analysis.

Animals↗

Postoperative detection of alpha-fetoprotein mRNA in blood as a predictor for metastatic recurrence of hepatocellular carcinoma.

BACKGROUND: We tested for the presence of alpha-fetoprotein (AFP) mRNA by using nested RT-PCR in the peripheral blood of hepatocellular carcinoma (HCC) patients who had undergone curative surgery, and investigated the occurrence of intrahepatic and/or extrahepatic metastasis thereafter, to reveal the optimal timing of blood sampling for the prediction of metastatic recurrence. METHODS: Twenty-nine patients with HCC, who had been operated on were analyzed with RT-PCR at several points during the clinical course, and examined for metastatic recurrence for 3-28 months (mean = 18.7 months) after surgery. RESULTS: The presence of AFP mRNA before surgery was significantly correlated with the tumor size (P = 0.017). Metastatic recurrence was associated with the postoperative detection of AFP mRNA (P < 0.001), but not with the preoperative and/or perioperative detection. Furthermore, AFP mRNA was detected in some cases that showed low serum AFP levels at recurrence. The recurrence-free period after the detection of AFP mRNA varied from 1 to 12 months. CONCLUSIONS: The postoperative detection of AFP mRNA is useful for the prediction of metastatic recurrence, and long-term follow up with this method should be conducted.

Adult↗

Analysis of hepatocellular carcinoma tumor growth detected in sustained responders to interferon in patients with chronic hepatitis C.

BACKGROUND: By analyzing a tumor growth of hepatocellular carcinoma (HCC) detected in sustained responders (SR) to interferon (IFN) therapy for chronic hepatitis C, we sought to determine the duration of follow up in SR that would be sufficient to detect HCC. In addition, we sought to elucidate the presence of HCC, which truly developed after the eradication of hepatitis C virus (de novo HCC development). METHODS: Tumor volume doubling time (DT) was calculated in a total of 46 cases of HCC detected in SR after IFN therapy. Based on DT, the annual growth rate was estimated for each tumor. Survival was compared between patients with HCC < or = 30 mm and patients with HCC > 30 mm in diameter. RESULTS: Doubling time in SR was similar to the previously reported DT of HCC irrespective of IFN therapy. However, extensive DT was observed in three HCCs despite relatively poor differentiation, which may represent de novo HCC development. In the analysis of tumor growth, all HCCs grew to exceed 20 mm in estimated diameter between 6 months and 7 years after the end of IFN therapy. Better survival was observed in patients with HCC < or = 30 mm in diameter compared with patients with HCC > 30 mm (P = 0.0107). In surviving patients, recurrences of HCC were very infrequent. CONCLUSIONS: We may be able to detect most HCC in SR between 6 months and 7 years after IFN therapy. However, we cannot neglect the presence of de novo HCC development after the eradication of HCV, which makes it difficult to determine completely sufficient follow-up duration after IFN therapy in this population.

Antiviral Agents↗

Vitamin C inhibits corpus gastritis in Helicobacter pylori-infected patients during acid-suppressive therapy.

BACKGROUND: Previous studies have shown that gastric acid suppression worsens corpus gastritis in Helicobacter pylori (H. pylori)-positive patients. We evaluated the effect of acid-suppressive therapy and vitamin C on H. pylori-associated gastritis. METHODS: Forty patients with reflux esophagitis were divided into three groups by the status of H. pylori and therapy: group A (n=15), H. pylori (+) and omeprazole 20 mg; group B (n=15), H. pylori (+) and omeprazole 20 mg + vitamin C 1200 mg; and group C (n=10), H. pylori (-) and omeprazole 20 mg. In all three groups, the mucosal interleukin (IL)-8 contents, H. pylori colonization density, neutrophil infiltration in the corpus, and serum gastrin were evaluated at entry and 2 weeks after starting therapy; in group B, serum vitamin C levels were also measured. RESULTS: In group A, the IL-8 contents and the degree of neutrophil infiltration during therapy exceeded those at entry, whereas in groups B and C, these values did not change significantly with treatment. Helicobacter pylori colonization density during therapy was similar to that at entry in all three groups. The serum gastrin (in all groups) and vitamin C levels (in group B) during therapy exceeded those at entry. CONCLUSIONS: Potent acid suppression worsens H. pylori-associated corpus gastritis, although such worsening gastritis may be inhibited by vitamin C.

Acids↗

Guidelines in the management of Helicobacter pylori infection in Japan.

BACKGROUND: In preparation of the approval of Helicobacter pylori therapy by the Japanese national health system, the board of directors of the Japanese Society for Helicobacter Research decided to prepare guidelines on the diagnosis and treatment of H. pylori infection for physicians in routine medical practice. METHODS: A guidelines preparation committee was formed and six meetings were held. Then, in December 1999, a consensus meeting was held in Kobe to obtain the opinions of general practitioners as well as experts from Europe, North America, and Asia. RESULTS: Helicobacter pylori eradication therapy is recommended in gastric or duodenal ulcer patients. Helicobacter pylori eradication therapy is recommended or gastric mucosa associated lymphoid tissue (MALT) lymphoma but it should be done at specialist institutions. The significance of H. pylori eradication therapy is still under evaluation in patients with hyperplastic polyps, chronic atrophic gastritis, non-ulcer dyspepsia and in patients after endoscopic mucosal resection of gastric cancer and after gastrectomy for gastric cancer. When diagnosing H. pylori infection, at least one of the tests requiring endoscopic biopsy (e.g. rapid urease test, histology, or culture) and tests not requiring biopsy (e.g. measurement of H. pylori antibody or urea breath test) should be used. Multiple tests are recommended to increase the accuracy. The drugs of first choice currently covered by the national health insurance system in Japan are: lansoprazole (30 mg) 1 capsule twice daily, amoxicillin (250 mg) 3 capsules twice daily, and clarithromycin (200 mg) 1-2 tablets twice daily. These three drugs should be administered after breakfast and dinner for 1 week. CONCLUSION: These guidelines are intended for utilization in routine medical practice after the Japanese national health system begins to cover the management of H. pylori infection.

Amoxicillin↗