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Biomedical subjects

K Aoyagi

Publications and source records attributed to K Aoyagi.

At least 109 records · Page 6Linked to original sources
PubMed1998

Treatment of herpes simplex esophagitis in an immunocompetent patient with intravenous acyclovir: a case report and review of the literature.

A 35-yr-old, immunocompetent male was admitted complaining of severe odynophagia. He was diagnosed as having herpes simplex esophagitis and was started on intravenous acyclovir 5 mg/kg every 8 h on the day of admission. His response was dramatic. Within 24 h he was virtually asymptomatic. Acyclovir therapy in immunocompetent adults with esophagitis has been described in only a handful of cases in the literature, although the therapy is well established in immunocompromised patients. We review the English literature and discuss the efficacy of the therapy. Acyclovir therapy may be beneficial in immunocompetent patients with particularly severe odynophagia.

Acyclovir↗
PubMed1998

Biosynthesis of methylguanidine in the hepatic peroxisomes and the effect of the induction of peroxisomal enzymes by clofibrate.

A state of peroxidation is one of the factors contributing to uremia. For example, we have reported that certain species of reactive oxygen, particularly the hydroxyl radical, play an important role in the biosynthesis of methylguanidine which contributes to toxicity in patients with uremia. However, it is uncertain which enzymes are involved in the synthesis of methylguanidine from creatinine. In this study, we attempt to show methylguanidine synthesis in the presence of peroxisomal enzymes that catalyze the beta-oxidation of fatty acids. In addition, we investigate the effect of clofibrate, which induces peroxisomal enzymes or glutathione peroxidase activity, on methylguanidine synthesis in the peroxisomal fraction. Male Wistar rats were fed with the chow containing 0.5% clofibrate to induce peroxisomal enzymes and control rats were fed with ordinary laboratory chow. Peroxisomal fractions were obtained from liver homogenates by centrifugation, and incubated with creatinine in 0.1 M potassium phosphate buffer pH 7.4 at 37 degrees C. Results show that methylguanidine is synthesized from creatinine concomitant with the synthesis of hydrogen peroxide from endogenous substrates in the peroxisomal fraction. This methylguanidine synthesis is inhibited by the addition of dimethylsulfoxide, glutathione, or sodium azide (p < 0.01). The rate of methylguanidine synthesis in clofibrate-treated rats was significantly less than that in control rats (p < 0.02). These results suggest that methylguanidine is synthesized in the peroxisomal fraction, and reactive oxygen species which are generated through this enzymatic reaction, participate in methylguanidine synthesis. Moreover, the induction of a scavenger system, especially glutathione peroxidase takes precedent over the generation of reactive oxygen species in peroxisomes treated with clofibrate.

Animals↗
PubMed1998

Falls among community-dwelling elderly in Japan.

Japanese have a lower incidence of hip fracture than Caucasians despite having lower bone mass. Hip fractures usually occur after a fall, and differing incidence rates of falls might explain the observed differences in hip fracture rates. To explore this hypothesis, we studied falls and related conditions among 1534 (624 men, 910 women) community-dwelling people aged 65 years and over in Japan and compared the prevalence of falls to Japanese-Americans living in Hawaii and to published studies of Caucasians. In Japan, 9% of the men and 19% of the women reported one or more falls during the past year. The prevalence of falls increased with age in both genders and was greater among women compared with men. In logistic regression models, having musculoskeletal disease, physical disability or limited activity increased the risk of falls by two to four times in both genders. Most fallers (92%) reported fear of future falls, and about one third of fallers reported that they went out less often as a result of their falls. Compared with native Japanese, the age-standardized prevalence of falls among Japanese-Americans was similar but about twice as high for Caucasians, which may explain the lower hip fracture risk of Japanese.

Accidental Falls↗
PubMed1998

Appearance of glucose-induced insulin release in fetal rat beta-cells.

Fetal rat pancreatic cells were isolated from pancreatic primordia on days 12-14 of pregnancy and cultured for 48 h in the presence of 5 mmol/l glucose. Insulin accumulation in the medium over the next 24 h was measured. Cultured cells from day 12 fetuses secreted about 1 fmol insulin per pancreas in response to 5 or 15 mmol/l glucose irrespective of whether 1 mmol/l tolbutamide, 400 mumol/l diazoxide, 5 mmol/l theophylline or 10 mmol/l mannoheptulose was present. In contrast, insulin released from day 13 cultured cells increased significantly from 3.0 +/- 0.6 to 6.2 +/- 2.2 fmol per pancreas, when the glucose concentration was raised. Tolbutamide increased, diazoxide and mannoheptulose decreased and theophylline had no effect on insulin release. Even more pronounced effects were found on insulin release from day 14 cultured cells, in which theophylline also increased the release. In addition, insulin release from cells from pregnancy day 14 was 75 +/- 16 amol/min per pancreas when the cells were perifused for 15-20 min in the presence of 5 mmol/l glucose within 3 h of isolation. Increasing the glucose concentration to 15 mmol/l or adding tolbutamide increased, whereas diazoxide decreased, insulin release in the freshly isolated cells. The insulin content of rat pancreata from pregnancy day 13 was 0.06 +/- 0.01 pmol per pancreas and increased approximately 10-fold every second day up to 6.7 +/- 0.9 pmol on day 17 of pregnancy. Between day 17 and 19 the pancreatic insulin content increased about fivefold to 39 +/- 2 pmol. The present data suggest that critical components of the insulin-secretory machinery, including ATP-regulated K+ channels, glucokinase and adenylate cyclase activities, are present in the developing beta-cell earlier than hitherto thought.

Animals↗
PubMed1998

Biodistribution studies on L-3-[fluorine-18]fluoro-alpha-methyl tyrosine: a potential tumor-detecting agent.

UNLABELLED: Iodine-123-alpha-methyl tyrosine has proven to be a promising SPECT agent for imaging amino acid uptake in tumors. We developed L-[3-(18)F]-alpha-methyl tyrosine (FMT) for PET studies. The aim of this study was to investigate its potential use as a tumor-detecting agent by using tumor-bearing mice. METHODS: We investigated the biodistribution in normal BALB/C mice and BALB/cA nude mice bearing human rectal cancer cell line (LS180) until 120 min postinjection. FMT tumor uptake at 60 min postinjection in mice with LS180 rectal cancer, RPM11788 B-cell lymphoma and MCF7 mammary cell carcinoma was assessed, and the results were compared with 18F-fluoro-2-deoxy-D-glucose (FDG) tumor uptake. The effect of competitive inhibition of large neutral amino acid transport system using unlabeled L-alanine was also investigated. RESULTS: The amount of FMT in blood fell to 1.05%ID/20 g at 60 min postinjection, whereas that in the pancreas was 15.2%ID/20 g, resulting in a high pancreas-to-blood ratio of 14.5. In other organs, initial uptake peaked at 5 min postinjection and then declined with time. In LS180 tumor-bearing mice, peak FMT uptake in tumor was observed at 60 min postinjection. Tumor-to-blood and tumor-to-muscle ratios ranged from 1.60 to 2.94 and from 2.79 to 3.25 over the 120-min observation period. Tumor uptake of FMT was clearly reduced by inhibition of the amino acid transport system. In mice with LS180 and MCF7 tumors, FMT tumor uptake at 60 min postinjection was significantly higher than FDG tumor uptake, whereas in RPM11788 lymphoma, uptake of FDG was significantly higher than FMT tumor uptake. Tumor-to-blood ratios of FMT in mice with LS180, RPMI1788 and MCF7 tumor at 60 min postinjection were 1.82, 5.88 and 3.56, respectively. CONCLUSION: FMT, like other fluorinated amino acids, may become a promising tumor-detecting agent for PET, assuming that efficient methods of radiosynthesis are developed.

Amino Acids↗
PubMed1998

[A case of glomerulonephritis with singular high titer of anticardiolipin antibody].

We report here a case of severe membranoproliferative glomerulonephritis with a singular high titer of anticardiolipin antibody (aCL). A 19-year-old Japanese female was admitted to Tsukuba Gakuen Hospital after complaining of general edema for 5 months. She had no past history of thrombosis, thrombocytopenia, or spontaneous abortion. Laboratory findings revealed that she had nephrotic syndrome and moderate renal dysfunction. Immunological test showed a high titer of aCL with a high-normal limit of antinuclear antibody, negativity for anti-beta(2) glycoprotein I antibody and negativity for anti-DNA antibody. In the renal biopsy tissue, most glomeruli showed global sclerosis and the remaining glomeruli revealed membranoproliferative change with crescent formation. Steroid therapy with warfarin and dipyridamole was effective and her renal function improved gradually. This case lacked the typical symptoms of primary antiphospholipid syndrome and did not satisfy the criteria of SLE. In spite of these findings, the singular high titer of aCL with membranoproliferative glomerulonephritis characterized this case.

Adult↗
PubMed1998

B-cell monoclonality precedes the development of gastric MALT lymphoma in Helicobacter pylori-associated chronic gastritis.

Little is known about the temporal changes in Helicobacter pylori density and B-cell clonality during the evolution from chronic gastritis to gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Biopsied specimens from 28 patients with chronic gastritis who developed gastric MALT lymphoma (group A) and from 24 similar patients who did not (group B) during an equivalent follow-up period (mean, 42 months) were retrospectively scored for histological features of MALT lymphoma (0 to 5) and H. pylori density (0 to 3). B-cell clonality was analyzed by polymerase chain reaction (PCR). During the observation period, the H. pylori density in group A decreased significantly in comparison with group B; the mean change in H. pylori density (final minus initial density) per 1000 days was -1.4 for group A and +0.2 for group B (P < 0.005). Monoclonality was detected more frequently in group A (79%) than in group B (21%; P < 0.005), and it preceded the histological evidence of malignant transformation in 64% of those patients who showed monoclonality in group A. These results suggest that H. pylori is thus more closely associated with the precursor or initial phase in the genesis of gastric MALT lymphoma than with the later phase, as its density decreases as the tumor progresses. The detection of B-cell monoclonality by PCR is thus of possible use for predicting the histological genesis of gastric lymphoma.

Adolescent↗
PubMed1998

[Reproducibility and wave analysis of multifocal electroretinography].

We studied the reproducibility of multifocal electroretinography by repeated measurements in normal subjects. We also analyzed the amplitude and implicit time of the waves. Nine healthy eyes including myopic cases (-4.1 D on average) of 9 normal males, aged 19 to 42 years, were the objects of study. We used a (Visual Evoked Response Imaging System III (VERIS III), by TOMEY Corp.) for multifocal electroretinography. Each eye was examined 4 times on different days. The stimulus elements consisted of 103 hexagons. The net recording time was 4 minutes. We used the coefficient of variation (standard deviation/average) of 4 measurements of response density as index of reproducibility. Poor fixation and blinking were important factors that affected the reproducibility. In all the 9 eyes, reproducibility of multifocal electroretinography, expressed as average of the coefficient of variation of all regions, was 22% on average. In 6 eyes with good fixation and without blinking, the reproducibility was 15% on average. In 6 eyes with good reproducibility, we analyzed three parameters of the focal response waves: all traces, quadrants and rings, as well as the amplitude and latency of the waves. These data served as controls. Our studies showed that the response density correlated closely with the amplitude and not with the latency in normal subjects.

Adult↗
PubMed1998

Specific transcription factors prognostic for prostate cancer progression.

We have previously identified (M. Wang et al., Oncol. Res., in press, 1998) an enhancer element [human tissue inhibitor of metalloproteinase-1 enhancer-1 (HTE)] for the human tissue inhibitor of metalloproteinase-1 promoter that binds a novel zinc finger, cysteine-rich transcription factor (CRTF). In this study, we have used electrophoretic mobility shift assays to examine the relative level of expression of CRTF, jun/fos, and IFN-gamma responsive signal transducer activators of transcription (STATs) that bind specific HTE, activator protein, and IFN-gamma (Fcy and interferon regulatory factor) response motifs in tumor lines and human prostate tissue [i.e., normal (n = 3); benign prostatic hyperplasia (BPH; n = 12); high grade prostate intraepithelial neoplasia (PIN; n = 10); and prostate cancer adenocarcinoma (PCA; n = 61) plus seminal vesicle (n = 10) tissues]. The data showed that CRTF was overexpressed in PCA (Gleason's score, 10>8>6>5>4) compared with BPH, PIN, seminal vesicle, and normal tissues. To a much lesser degree, jun/fos and STAT 1 were also elevated in PCA compared to BPH, PIN, and normal tissues. In addition, blinded studies showed that CRTF and jun/fos were present at low levels in organ-confined specimens but at significantly elevated levels (P < 0.001) in samples exhibiting capsular penetration and localized spread, which indicated that CRTF and perhaps jun/fos were markers for cancer progression.

Binding Sites↗
PubMed1997

Cloning of mDEAH9, a putative RNA helicase and mammalian homologue of Saccharomyces cerevisiae splicing factor Prp43.

Yeast splicing factor Prp43, a DEAH box protein of the putative RNA helicase/RNA-dependent NTPase family, is a splicing factor that functions late in the pre-mRNA splicing pathway to facilitate spliceosome disassembly. In this paper we report cDNA cloning and characterization of mDEAH9, an apparent mammalian homologue of Prp43. Amino acid sequence comparison revealed that the two proteins are approximately 65% identical over a 500-aa region spanning the central helicase domain and the C-terminal region. Expression of mDEAH9 in S. cerevisiae bearing a temperature-sensitive mutation in prp43 was sufficient to restore growth at the nonpermissive temperature. This functional complementation was specific, as mouse mDEAH9 failed to complement mutations in related splicing factor genes prp16 or prp22. Finally, double label immunofluorescence experiments performed with mammalian cells revealed colocalization of mDEAH9 and splicing factor SC35 in punctate nuclear speckles. Thus, the hypothesis that mDEAH9 represents the mammalian homologue of yeast Prp43 is supported by its high sequence homology, functional complementation, and colocalization with a known splicing factor in the nucleus. Our results provide additional support for the hypothesis that the spliceosomal machinery that mediates regulated, dynamic changes in conformation of pre-mRNA and snRNP RNAs has been highly conserved through evolution.

Amino Acid Sequence↗
PubMed1997

A novel nonenzymatic pathway for the generation of nitric oxide by the reaction of hydrogen peroxide and D- or L-arginine.

Nitric oxide (NO) is a biologically active molecule known to be enzymatically synthesized from L-arginine in the presence of NO synthetase (NOS). In this study, we demonstrate a novel non-enzymatic pathway for NO synthesis involving hydrogen peroxide and D- or L-arginine. We employed two measures of NO generation. The first consists in the demonstration of the oxidative metabolites of NO (NO2 + NO3 = NOx) and the second is the confirmatory finding of chemiluminescence derived from NO. The results show that NOx increases in the incubation mixture containing hydrogen peroxide coupled with D-arginine, L-arginine, L-canavanine, and even the NOS inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME). However, chemiluminescence was detected only from the reactions of hydrogen peroxide and D- or L-arginine and was diminished by the addition of carboxy-2-phenyl-4, 4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide (PTIO), a specific scavenger of NO, confirming NO generation in the reaction.

Amino Acids↗
PubMed1997

Synchronous and metachronous primary gastric lymphoma and adenocarcinoma: a clinicopathological study of 12 patients.

BACKGROUND: The occurrence of both malignant gastric lymphoma and adenocarcinoma in the same patient is very rare. METHODS: The resected specimens from 12 patients who had both primary gastric lymphoma and adenocarcinoma were analyzed using immunohistochemistry and in situ hybridization. RESULTS: Two different tumors were found synchronously in 10 patients (5 with independent tumors and 5 with contiguous/collision tumors) and metachronously in 2. The size of the lymphomas (mean, 7.2 cm) was larger than that of the adenocarcinomas (mean, 3.6 cm) (P < 0.005). Histologically, 9 of the 12 lymphomas (75%) were mucosa-associated lymphoid tissue lymphomas, and all lymphomas invaded the deep portion of the submucosa or deeper. Conversely, 10 of the 12 adenocarcinomas (83%) were early carcinomas. Six adenocarcinomas were intestinal type, whereas the other 6 were diffuse type. The MIB-1 index of the adenocarcinomas (mean, 50.4%) was higher than that of the lymphomas (mean, 29.3%) (P < 0.05). Helicobacter pylori (H. pylori) was documented in all 12 patients, whereas Epstein-Barr virus-encoded RNA 1 was detected in only 2. During the follow-up period after surgery, 6 patients died, 4 due to adenocarcinoma. The survival probability of all 12 patients appeared to be similar to that of previously reported patients with gastric adenocarcinoma alone, and was significantly worse than that of the 217 patients with gastric lymphoma alone (P < 0.05). CONCLUSIONS: An H. pylori infection is considered to be associated with the development of these double malignancies. In many such synchronously observed cases, lymphomas may precede carcinogenesis, while the prognosis appears to be more closely associated with the adenocarcinoma than the lymphoma.

Adenocarcinoma↗
PubMed1997

Helicobacter pylori and primary gastric lymphoma. A histopathologic and immunohistochemical analysis of 237 patients.

BACKGROUND: Few previous articles have analyzed the relation between infection with Helicobacter pylori (H. pylori) and primary gastric lymphoma in a large number of patients. METHODS: Resected and biopsied specimens from 237 patients with primary gastric lymphoma were investigated for H. pylori using hematoxylin and eosin stain, modified Giemsa stain, and immunohistochemistry. These specimens were compared with specimens from 29 patients with chronic active gastritis, 33 with peptic ulcers, and 41 with gastric carcinoma. RESULTS: H. pylori was detected in 145 of 237 patients (61%) with gastric lymphoma. The frequency of H. pylori positivity was higher in patients with lymphoma restricted to the mucosa and submucosa (76%) than in those with lymphoma invading beyond the submucosa (48%) (P < 0.001), and was also higher in patients with low grade mucosa-associated lymphoid tissue lymphoma (72%) than in those with high grade tumors (55%) (P < 0.05). The frequency of H. pylori positivity in patients with lymphoma was lower than in those with chronic active gastritis (100%) (P < 0.001) or peptic ulcer (91%) (P < 0.05). In patients with lymphoma restricted to the mucosa and the superficial portion of the submucosa, the frequency of H. pylori positivity (90%) was as high as that observed in patients with chronic active gastritis and peptic ulcer. The H. pylori grading score for patients with lymphoma (0.9 +/- 1.0) was lower than for those with chronic active gastritis (1.9 +/- 0.8) (P < 0.001), peptic ulcers (2.2 +/- 1.0) (P < 0.001), or gastric carcinoma (1.2 +/- 1.1) (P < 0.05). CONCLUSIONS: These results suggest that H. pylori is more likely to be associated with early states of primary gastric lymphoma than with advanced states. Thus, H. pylori may disappear during the progression of primary gastric lymphoma.

Adolescent↗
PubMed1997

Thyroid neoplasia and familial adenomatous polyposis/Gardner's syndrome.

This study was conducted to clarify the actual morbidity and clinicopathologic features of thyroid neoplasia in patients with familial adenomatous polyposis. We analyzed the clinical records of 49 Japanese patients with familial adenomatous polyposis diagnosed at our institute. Six of these patients had thyroid neoplasias (3 carcinomas, 2 adenomas, and 1 of unknown histology). Among 17 patients (11 men and 6 women) who had been examined by thyroid ultrasonography or in whom postmortem examination was performed; we categorized 6 patients with thyroid tumor as the TT group, and the remaining 11 without thyroid tumor as the NTT group. The clinical features of the two groups were compared. Thyroid neoplasia was detected by physical examination in 2.3% of 43 patients so examined and was detected in 25% of 8 patients examined by thyroid ultrasonography, and in 44% of the 9 patients subjected to postmortem examination. There were no significant differences between the TT and NTT groups in gender; age at first admission, colectomy, and last follow-up visit; number of colonic polyps; or in presence of colorectal cancers, gastroduodenal adenomas, gastric fundic gland polyposis, retinal pigmented lesions, or extraintestinal tumors. The thyroid gland is frequently affected in patients with familial adenomatous polyposis, but there may be no association between thyroid neoplasia and other clinical manifestations.

Adenomatous Polyposis Coli↗
PubMed1997

Endoscopic hydrostatic balloon dilation of ulcer-induced pyloric stenosis in rheumatoid arthritis and secondary amyloidosis.

We describe a 50-year-old Japanese woman with rheumatoid arthritis who presented with near-complete gastric outlet obstruction. The patient also suffered from secondary gastrointestinal and cardiac amyloidosis. Gastroscopy revealed multiple huge gastric antral ulcers in which amyloid deposits were identified on histologic examination. The ulcers became scars after treatment with omeprazole, which cause in severe pyloric stenosis. Endoscopic hydrostatic balloon dilation under fluoroscopic guidance was performed twice for 10 min. The pyloric outlet remained sufficiently patent 22 months later.

Amyloidosis↗