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Biomedical subjects

K Fujimoto

Publications and source records attributed to K Fujimoto.

At least 19 recordsLinked to original sources

Expression of the gene for a membrane-bound fatty acid receptor in the pancreas and islet cell tumours in humans: evidence for GPR40 expression in pancreatic beta cells and implications for insulin secretion.

AIMS/HYPOTHESIS: G protein-coupled receptor 40 (GPR40) is abundantly expressed in pancreatic beta cells in rodents, where it facilitates glucose-induced insulin secretion in response to mid- to long-chain fatty acids in vitro. However, GPR40 gene expression in humans has not been fully investigated, and little is known about the physiological and pathophysiological roles of GPR40 in humans. The aim of this study, therefore, was to examine GPR40 expression and its clinical implications in humans. METHODS: GPR40 mRNA expression in the human pancreas, pancreatic islets and islet cell tumours was analysed using TaqMan PCR. RESULTS: GPR40 mRNA was detected in all human pancreases collected intraoperatively. It was enriched approximately 20-fold in isolated islets freshly prepared from the pancreases of the same individuals. The estimated mRNA copy number for the GPR40 gene in pancreatic islets was comparable to those for genes encoding sulfonylurea receptor 1, glucagon-like peptide 1 receptor and somatostatin receptors, all of which are known to be expressed abundantly in the human pancreatic islet. A large amount of GPR40 mRNA was detected in insulinoma tissues, whereas mRNA expression was undetectable in glucagonoma or gastrinoma. The GPR40 mRNA level in the pancreas correlated with the insulinogenic index, which reflects beta cell function (r=0.82, p=0.044), but not with glucose levels during the OGTT, the insulin area under the OGTT curve or the index for the homeostasis model assessment of insulin resistance (HOMA-IR). CONCLUSIONS/INTERPRETATION: The present study provides evidence for GPR40 gene expression in pancreatic beta cells and implicates GPR40 in insulin secretion in humans.

Adult↗

A simple gamma ray direction finder.

One of the simplest gamma spectrometry systems that could provide the directional information of incident gamma rays has been developed. The system consists of a 3'' x 3'' phi NaI (Tl) scintillator, a specially shaped lead shield, and software. The measurement was carried out four times by rotating the shield position along the axis of the detector to obtain four energy spectra at one location. Four count rates at a special region of interest in the spectra were fed into the software for determining incident directions of gamma rays. Experiments using (137)Cs and (54)Mn at the same time demonstrated that the direction of gamma rays from several dominant sources from any direction could be identified with good precision by the total measurement time of 10 to 20 min. The system could be used to identify the locations of missing radioactive sources or the cause of elevation in ambient radiation dose rates. The disadvantages of the present system are follows: (1) It requires four time measurements at one location; (2) It can provide one pseudo incident angle when several contamination sources exist around the detector system and emit the same energy gamma rays; and (3) It can scan only one plane geometry that is usually chosen as the horizontal plane.

Equipment Design↗

Dose estimation of a soft X-ray exposure incident.

A dose reconstruction was carried out on a case in which a worker was exposed to soft x rays using time motion studies, an ionization chamber for low energy photon measurements, and CdZnTe (CZT) spectrometry. The worker estimated his dose to be over 600 mSv. However, the doses to the skin and testes were evaluated to be 14 and 0.44 mSv, respectively, with an effective dose of 0.099 mSv.

Body Burden↗

Effect of CYP2C19 polymorphism on the safety and efficacy of omeprazole in Japanese patients with recurrent reflux oesophagitis.

BACKGROUND: The polymorphic enzyme cytochrome P450 2C19 affects omeprazole metabolism. This influence on metabolism might affect serum gastrin levels, and safety, during long-term treatment of reflux oesophagitis. AIM: To examine the relationship between cytochrome P450 2C19 genotype and the safety profile of long-term omeprazole treatment. METHODS: A total of 119 Japanese patients with recurrent reflux oesophagitis underwent cytochrome P450 2C19 genotyping prior to receiving daily omeprazole 10 mg or 20 mg for 6-12 months, during which adverse event frequency, serum gastrin levels and endoscopic findings were monitored. RESULTS: The incidences of adverse events, serious adverse events and adverse events leading to withdrawal did not differ between homozygous extensive metabolizer (n = 46), heterozygous extensive metabolizer (n = 53) or poor metabolizer (n = 20) groups. In all genotype groups, serum gastrin increased during the first 3 months of dosing but stabilized thereafter. No significant differences were seen either in the rate of reflux oesophagitis healing or symptom improvement among genotype groups. CONCLUSIONS: Long-term treatment with omeprazole was well-tolerated in Japanese patients, irrespective of their cytochrome P450 2C19 metabolic genotype, indicating that dose adjustment depending on metabolic genotype is not required during treatment with omeprazole.

Adult↗

Serial high resolution CT in non-specific interstitial pneumonia: prognostic value of the initial pattern.

AIM: To assess the relationship between initial CT pattern and serial changes in CT findings and pulmonary function tests (PFTs) in patients with non-specific interstitial pneumonia (NSIP). MATERIALS AND METHODS: Serial high resolution (HR) CTs and PFTs were retrospectively analyzed in 38 cases of histologically proven NSIP, including 4 with cellular NSIP, 13 with mixed cellular and fibrotic NSIP, and 21 with fibrotic NSIP. The presence and extent of various CT findings were assessed. A fibrosis index (defined as the ratio of the extent of a reticular/honeycomb pattern to the overall extent of abnormal parenchyma) was derived. RESULTS: The predominant CT pattern was reticular/honeycomb in 27 (84%) cases and ground-glass/consolidation in 6 (16%) cases. Between scans, mean disease extent reduced by 5.2%. Disease extent reduced by >10% in 13 (34%) and increased by >10% in 6 (16%) patients. Histopathological subtype of NSIP did not correlate with individual CT pattern, predominant pattern, fibrosis index or serial change in disease extent on CT or PFTs. Response on follow-up CT was associated with fibrosis index, predominant pattern and extent of consolidation on initial CT. CONCLUSION: In NSIP disease, progression on CT correlates with the predominant CT pattern, fibrosis index, and extent of consolidation but not with histopathological subtype. An inflammatory (ground-glass/consolidation) predominant pattern is associated with better outcome in terms of disease extent on HRCT.

Disease Progression↗

Transluminal coil embolization of an inferior gluteal artery aneurysm by ultrasound-guided direct puncture of the target vessel.

Pseudoaneurysms of the inferior gluteal artery are rare. We describe a case of an inferior gluteal pseudoaneurysm that presented as a painful mass in the buttock. A percutaneous thrombin injection under ultrasound guidance failed to occlude the sac, probably due to the wide neck of the aneurysm. Subsequently, transluminal coil embolization by ultrasound-guided direct puncture of the inferior gluteal artery achieved complete thrombosis of the sac. Ultrasound-guided coil embolization is recommended in the treatment of peripheral aneurysms where catheter placement using conventional interventional procedures is difficult.

Aged↗

Pentosidine and its deposition in renal tissue in renal transplantation.

BACKGROUND: Advanced glycation end products (AGEs) accumulate in lesions of arteriosclerosis, Alzheimer's disease, rheumatoid arthritis, diabetic retinopathy, and diabetic nephropathy. Among AGEs, chemical quantification and immunohistologic methods for pentosidine have been established. Free pentosidine-eliminated by renal excretion- is mainly affected by renal function. In this study, we measured concentrations of plasma free and total pentosidine and immunohistologically investigated kidney graft biopsy specimens in patients after renal transplantation to investigate the renal function, plasma free and total pentosidine, and its relationship with deposition in the renal tissue. PATIENTS AND METHODS: In 28 patients who underwent renal transplantation from 1996 to 2003, we measured the time course of plasma concentrations of free pentosidine, total pentosidine, and serum creatinine starting right after renal transplantation. Thirty-four graft biopsy specimens were immunohistologically investigated using anti-pentosidine antibody. Plasma free and total pentosidine, and serum creatinine were measured at the same time. RESULTS: Plasma free and total pentosidine were positively correlated with serum creatinine. Plasma free pentosidine and serum creatinine reached nadir values on day 34.2 +/- 14.2, when the blood concentrations were 5.1 +/- 1.6 pmol/mL and 1.7 +/- 0.7 mg/dL, respectively. Plasma total pentosidine reached a nadir on day 116.5 +/- 39.7 when the plasma concentration was 4.0 +/- 1.5 pmol/mg. We correlated the time required to reach the nadir of plasma free and total pentosidine concentrations. However, neither the concentration of plasma free nor plasma total pentosidine at nadir correlated with serum creatinine. The intensity of immunostaining with anti-pentosidine antibody in proximal tubular cells was graded as weakly positive, positive, or strongly positive. Significant differences were obtained among plasma free pentosidine values between the weakly positive and strongly positive groups. CONCLUSIONS: Renal transplantation improves renal function and decreases renal excretion of free pentosidine. Accordingly, total pentosidine also decreases. However, the concentrations of plasma free and total pentosidine at nadir varied among individuals; the blood concentrations were not determined by renal function alone. It was suggested that deposition of pentosidine in proximal tubular cells was more severe among patients with higher plasma free pentosidine and serum creatinine values.

Adult↗

Trial of remote telemedicine support for patients with chronic respiratory failure at home through a multistation communication system.

To create and test a multistation telemedicine support system, three remote locations were connected: the homes of two patients with chronic respiratory failure, the hospital of the attending physician, and the hospital of the pulmonary specialist. Real-time connections were set up between the three locations. Medical history and biologic variables were noninvasively recorded, including blood pressure, arterial oxygen saturation, three-lead electrocardiogram, and end-tidal carbon dioxide. Both physicians shared in these data real-time. If necessary, the respiratory specialist could provide medical advice to the attending physician based on the patient's condition. The trial program resulted in the same information being exchanged remotely using the multi-station telemedicine system that would be exchanged in a direct, face-to-face encounter. This result, together with the improvement in quality of life and the establishment of appropriate treatment and cooperation between the respiratory specialist and attending physician, suggests our system can be considered useful and promising for further use.

Aged↗

Prevention of the rehaemorrhage of bleeding peptic ulcers: effects of Helicobacter pylori eradication and acid suppression.

AIM: This study aimed to investigate the consequences of Helicobacter pylori eradication and acid suppression on rehaemorrhage caused by bleeding peptic ulcers. METHODS: A total of 320 patients who had been diagnosed with bleeding peptic ulcers between January 1994 and December 2001 were included in the study. Cases between 1994 and 1997, prior to the introduction of eradication therapy, were assigned to group A, whereas those between 1998 and 2001, after the eradication therapy, were assigned to group B. RESULTS: Of the 320 cases, 162 were designated as group A (113 gastric ulcers and 49 duodenal ulcers) and 158 as group B (116 and 42, respectively). Rehaemorrhage occurred in 24 cases (15%) and five cases (3%) in groups A and B, respectively, presenting a significantly decreased rate of rehaemorrhage in group B. Among those without eradication, rehaemorrhage was observed in 15 of 128 cases (12%) that received treatment with histamine(2)-receptor antagonist (famotidine), and 14 of 142 cases (10%) treated with proton-pump inhibitors, with no significant difference between the two. CONCLUSIONS: Helicobacter pylori eradication lowered the rates of rehaemorrhage. Treatment with histamine(2)-receptor antagonist or proton-pump inhibitors did not produce a difference in the rate of rehaemorrhage.

Adult↗

Quantification of red blood cell fragmentation by the automated hematology analyzer XE-2100 in patients with living donor liver transplantation.

The fragmented red cell (FRC) is a useful index for diagnosing and determining the severity of thrombotic thrombocytopenic purpura (TTP), thrombotic microangiopathy (TMA) and other similar conditions, as it is found in peripheral blood in patients with these diseases. The FRC expression rate has conventionally been determined by manual methods using smear samples. However, it is difficult to attain accurate quantification by such methods as they are time consuming and prone to a great margin of error. With cases of living donor liver transplantation, the current study examined the possibility of using a multi-parameter automated hematology analyzer, the XE-2100 (Sysmex Corporation) for FRC quantification. While there was a notable correlation between the manual and automated measurements, the manual measurement resulted in higher values. This suggested remarkable variations in judgment by individuals. The FRC values had a significant correlation with the reticulocyte count, red blood cell distribution width (RDW), fibrin/fibrinogen degradation products (P-FDP) and lactate dehydrogenase (LDH) among the test parameters, and this finding was consistent with the clinical progression in patients. The automated method can offer precise measurements in a short time without inter-observer differences, meeting the requirement for standardization. The determination of FRC count (%) by the XE-2100 that enables early diagnoses and monitoring of TTP or TMA will be useful in the clinical field.

Adolescent↗

Effective in vivo purging with rituximab and autologous peripheral blood stem cell transplantation in a woman with CD5 positive primary cutaneous diffuse large B-cell lymphoma.

Generalized subcutaneous tumors developed without any other sites of the disease in a Japanese woman. Skin biopsy revealed CD5(+) and CD20(+) atypical diffuse large cells infiltrating subcutaneous tissues. The diagnosis was CD5(+) primary cutaneous diffuse large B-cell lymphoma. Tumor-specific PCR showed the existence of malignant cells in the peripheral blood and bone marrow. After three cycles of chemotherapy, she was remained in partial remission. Peripheral blood stem cells (PBSC) were harvested after the fourth cycles of chemotherapy combined with rituximab for in vivo purging. The contamination of tumor cells in PBSC was negative with PCR. She then underwent autologous peripheral blood stem cell transplantation using purged PBSC and has remained in complete remission for the past 24 month.

Antibodies, Monoclonal↗

Clock gene expression in the submandibular glands.

Clock genes, which mediate molecular circadian rhythms, are expressed in a circadian fashion in the suprachiasmatic nucleus and in various peripheral tissues. To establish a molecular basis for circadian regulation in the salivary glands, we examined expression profiles of clock-related genes and salivary gland-characteristic genes. Clock-related genes-including Per1, Per2, Cry1, Bmal1, Dec1, Dec2, Dbp, and Reverbalpha-showed robust circadian expression rhythms in the submandibular glands in 12:12-hour light-dark conditions. In addition, a robust circadian rhythm was observed in amylase 1 mRNA levels, whereas the expression of other salivary-gland-characteristic genes examined was not rhythmic. The Clock mutation resulted in increased or decreased mRNA levels of Per2, Bmal1, Dec1, Dec2, and Dbp, and in Cry1-/- background, Cry2 disruption also increased or decreased mRNA levels of these clock-related genes and the amylase 1 gene. These findings indicate that the Clock- and Cry-dependent molecular clock system is active in the salivary glands.

ARNTL Transcription Factors↗

Phase I trial of nedaplatin and paclitaxel for patients with non-small cell lung cancer.

A phase I study was conducted to evaluate the maximum tolerated dose and feasibility of combination with nedaplatin (NDP) and paclitaxel in patients with non-small cell lung cancer (NSCLC). Fifteen patients under 75 years old, with unresectable NSCLC who had not previously received chemotherapy or radiotherapy, with a performance status of 0-1, were enrolled. The dose escalation levels (NDP/Paclitaxel; mg/m2 day 1) were 80/150 (level 1), 80/180 (level 2), 90/180 (level 3) and repeated every 28 days. All patients receiving level 3 had dose-limiting toxicity. One patient developed grade 4 neutropenia with infection, two had incomplete recovery of neutropenia and thrombocytopenia by the 28th day after the first cycle of chemotherapy. Non-hematologic toxicities, including nephrotoxicity, nausea/vomiting, alopecia, and hypersensitivity reaction, were tolerated. Three of the 15 patients achieved partial responses. We concluded that the recommended dose was paclitaxel 180 and NDP 80 mg/m2 due to the hematologic toxicity.

Adult↗

Airway inflammation during stable and acutely exacerbated chronic obstructive pulmonary disease.

The aim of this study was to clarify the mechanism of increased airway inflammation during an acute exacerbation. A total of 68 chronic obstructive pulmonary disease patients in a stable phase were enrolled and followed-up for 2-3 yrs. Inflammatory cells were analysed, and interleukin (IL)-8, neutrophil elastase, eotaxin, tryptase and RANTES (regulated on activation, normal T-cell expressed and secreted) were measured in sputum, both in a stable phase and during acute exacerbation. Out of 68 patients, 30 (unstable group) developed an acute exacerbation and expectorated adequate sputum during exacerbation. Thirty-two patients (stable group) did not develop any exacerbation for 2-3 yrs. The number of neutrophils, lymphocytes and eosinophils, and the levels of IL-8, eosinophil cationic protein (ECP), eotaxin and tryptase in sputum obtained from patients in both groups during the stable phase were significantly higher than those from healthy nonsmokers. There were no significant differences in cell analysis and biomarkers between the two groups, but patients in the unstable group showed more severe airflow limitation. In the unstable group, total cells, lymphocytes, neutrophils and eosinophils, and IL-8, neutrophil elastase, ECP and RANTES levels were significantly increased during an exacerbation from values in a stable phase. These findings suggest that exacerbation of chronic obstructive pulmonary disease may associate with additional increases in airway inflammation mediated by neutrophils, lymphocytes, eosinophils, interleukin-8 and RANTES.

Acute Disease↗

Characterization of novel squamous cell carcinoma antigen-related molecules in mice.

The squamous cell carcinoma antigen 1 (SCCA1) and SCCA2 are unique serpins that can inhibit cysteine proteinases. SQN-5, their mouse ortholog, has already been identified, and its inhibitory property has been characterized; however, its biological role has remained undefined. Furthermore, no other mouse homolog of SQN-5 has been known. We characterize three mouse members of SCCA-related molecules including SQN-5 in this article. Serpinb3a (SQN-5) and Serpinb3b, but not Serpinb3c, were functional, inhibiting both serine and cysteine proteinases with different inhibitory profiles due to the difference of two amino acids in their reactive site loops. Serpinb3a was ubiquitously expressed in most tissues, whereas expression of Serpinb3b was limited to keratinocytes. Keratinocytes secreted both SCCA-related proteins, Serpinb3a and Serpinb3b. These results indicate that Serpinb3a and Serpinb3b may play different roles by inhibiting intrinsic or extrinsic proteinases with different expression distributions and different inhibitory profiles.

Amino Acid Sequence↗