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Biomedical subjects

Y Hirose

Publications and source records attributed to Y Hirose.

At least 145 records · Page 8Linked to original sources

[Infected emphysematous bullae in a patient with diabetes mellitus].

A 42-year-old woman with diabetes mellitus was admitted to our hospital because of fever, coughing, and dyspnea. Coarse crackles were audible and respiratory sounds were weak in the right lung field. Laboratory examination revealed a high erythrocyte sedimentation rate, a high level of serum C-reactive protein, a high blood sugar level, and hypoxemia. A chest roentgenogram revealed cystic lesions with fluid levels, and an infiltration shadow in the right lung field. A chest computed tomographic scan revealed many cystic lesions with fluid levels and an infiltration shadow. Our diagnosis was infected emphysematous bullae. A tube was inserted percutaneously for drainage and to allow injection of antibiotics into the cystic lesion. The cystic lesion then vanished. Percutaneous drainage and washing with antibiotics can be used to treat infected emphysematous bulla that have thick closed cystic walls.

Adult↗

[Diffuse large B-cell lymphoma mainly involving the heart and showing t(8;14) (q24;q32) with c-myc rearrangement].

A 77-year-old man was admitted because of massive pericardial effusion and cardiac tumor. Cytological examination of the effusion and histological examination of a subcutaneous tumor in the chest wall revealed diffuse large B cell lymphoma. The immunophenotype of tumor cells was CD5+ CD20+ CD22+ CD38+ HLA-DR+ CD19-. Chromosome analysis revealed complex abnormal karyotypes containing t(8;14) (q24;q32). C-myc gene rearrangement was shown by Southern blotting. Chemotherapy with pirarubicin, cyclophosphamide, vincristin, and prednisolone (THP-COP) was not effective for his lymphoma. He suffered from cardiac tamponade and died at 5 months after diagnosis. Autopsy revealed a large cardiac tumor, extensive epicardial infiltration, tiny tumors in the lung and pancreas, but no lymphadenopathy, the combination of which suggested a primary cardiac lymphoma. Immunohistochemistry for p53 protein showed nuclear staining of more than 50% of the lymphoma cells. In situ hybridization for EBER-1 was negative. Rearrangement of c-myc gene and overexpression of p53 protein are usually observed in Burkitt's lymphoma and some cases of high grade lymphomas including AIDS-associated non-Hodgkin lymphomas. In this case the association of these molecular findings and resistance to chemotherapy is suggested.

Aged↗

Mechanisms of KE298, 2-acetylthiomethyl-3-(4-methylbenzoyl) propionic acid, to suppress abnormal synovial cell functions in patients with rheumatoid arthritis.

OBJECTIVE: 2-Acetylthiomethyl-3-(4-methylbenzoyl) propionic acid, KE298, a derivative or propionic acid developed in Japan has been shown to be effective for suppressing disease activity of rheumatoid arthritis (RA) in clinical trials in Japan. It is thus a candidate as a new disease modifying antirheumatic drug (DMARD). We analyzed effects of KE298 on synovial fibroblast-like cells in patients with RA to obtain insight into the clinical application of this medication. METHODS: RA synovial fibroblast-like cells were co-cultured with KE298 at 10(-4)-10(-5) M in the presence or absence of tumor necrosis factor-alpha 2 ng/ml, and their subsequent proliferative responses and proinflammatory cytokine and matrix metalloproteinase (MMP) production at the mRNA and protein levels were measured. Effects of KE298 on MMP-1 gene transcription and AP-1 transcription factor expression of RA synovial cells were studied by chloramphenicol acetyltransferase assay and gel shift assay, respectively. RESULTS: KE298 inhibited proliferation of RA synovial cells, proinflammatory cytokine production, and MMP-1 production mainly by reducing their transcription via downmodulation of AP-1 transcription factor. CONCLUSION: KE298 inhibits aberrant synovial cell functions of patients with RA by downregulating gene transcription, suggesting clinical application and usefulness of this new DMARD.

Antirheumatic Agents↗

Chemoprevention by naturally occurring and synthetic agents in oral, liver, and large bowel carcinogenesis.

A number of naturally occurring compounds and several related synthetic agents were confirmed to exert chemopreventive properties against carcinogenesis in the digestive organs. Phenolic compounds, widely distributed as plant constituents, possess chemopreventive activities in tongue, liver, and large bowel of rodents. Of them, a simple phenolic protocatechuic acid seems to be a promising compound. Organosulfur compounds contained in the cruciferous vegetables and known to activate detoxifying enzymes are regarded as a candidate group for cancer preventive agents. We proved a strong protective effect of S-methylmethanethiosulfonate, a constituent in these vegetables, on azoxymethane (AOM)-induced large bowel carcinogenesis. Some oxygenated carotenoids (xanthophylls) are reported to have antitumor effects. Naturally occurring xanthophylls astaxanthin and canthaxanthin have considerable preventive activities on 4-nitroquinoline-1-oxide (4-NQO)-induced tongue carcinogenesis and AOM-induced large bowel carcinogenesis. A novel synthesized retinoidal butenolide, KYN-54, which suppresses large bowel as well as tongue carcinogenesis could be a useful agent for prevention of digestive organ cancers. Some trace elements are known to have anticarcinogenic effects. Magnesium hydroxide, a protective agent in colorectal carcinogenesis, inhibits c-myc expression and ornithine decarboxylase activity in the mucosal epithelium of the intestine. Our results show that many agents with preventive effects in tongue, liver, and large bowel control carcinogen-induced hyperproliferation of cells in these organs. Carcinogens used to induce large bowel cancers also induce apoptosis in the target sites. Telomerase activity is increased in the tissues of preneoplastic as well as neoplastic lesions in experimental models such as dimethylbenz[a]anthracene-induced oral carcinogenesis in hamsters. These could be useful biomarkers in studies for cancer chemoprevention.

Animals↗

Characteristics of Epstein-Barr virus-associated gastric carcinoma with lymphoid stroma in Japan.

BACKGROUND: Gastric carcinoma with lymphoid stroma (GCLS), known to have a more favorable prognosis than ordinary gastric carcinoma, has been suggested to be closely associated with the Epstein-Barr virus (EBV). However, there are many clinicopathologic problems that remain unsolved. METHODS: In 21 patients, 26 GCLS lesions and 4 non-GCLS intramucosal adenocarcinomas that developed synchronously or metachronously with GCLS were examined for EBV involvement by in situ hybridization (ISH) and were analyzed clinicopathologically. In addition, nine patients who had advanced gastric carcinoma with massive liver metastases, who showed good response to chemotherapy and had prolonged survival, were examined for the presence or absence of EBV-associated GCLS. RESULTS: On ISH with EBV-encoded small RNAs, diffuse hybridization signals were noted in 22 (84.6%) of 26 GCLS. Hybridization signals were also noted in all four non-GCLS adenocarcinomas accompanying GCLS. As a result, hybridization signals were noted in nine of ten cancerous lesions in four cases of synchronous multiple cancers and in all five cancerous lesions in two cases of metachronous multiple cancers. Long term survivors with liver metastases included two patients with EBV-associated GCLS. CONCLUSION: Approximately 84.6% of GCLS were related to EBV. EBV-associated GCLS constitutes one-half of the EBV-infected stomach cancers in our institution. The complete response and long term survival after conventional chemotherapy of two patients with Stage IV GCLS suggests that this form of gastric carcinoma may be especially sensitive to this treatment. The identification of EBV-associated synchronous multicentric cancers of both GCLS and non-GCLS type suggests that EBV infection may be an early event in the induction process of these tumors.

Adult↗

Localization of Bax and Bcl-2 proteins, regulators of programmed cell death, in the human central nervous system.

Bax and Bcl-2 proteins are identified as regulating molecules for programmed cell death. In the central nervous system, programmed cell death or apoptosis is considered to be an important phenomenon that is related to neuron vulnerability to a variety of toxic effects, including ischaemic insult. In this study, localization of Bax and Bcl-2 proteins was investigated in the human central nervous system using autopsy cases without any neurological disorder. Results were compared with findings in the rat. Most neurons in human cerebral cortex, basal ganglia and brain stem were positive for both Bax and Bcl-2 proteins, whereas Purkinje cells in cerebellum and neurons in hippocampal CA1, CA2 and CA3 regions were positive for Bax but negative or weakly positive for Bcl-2. Glial cells examined in all sections were negative for both proteins. Choroid plexus, ependymal cells and arachnoid villi showed positive reactivity for both proteins. A possible relationship between the localization of Bax or Bcl-2 proteins and the cell vulnerability in central nervous system is discussed.

Animals↗

Intra-arterial blood gas monitoring system: more accurate values can be obtained.

OBJECTIVE: To compare values measured by a continuous intra-arterial blood gas monitoring system with those measured by conventional blood gas analyzer for the assessment of the clinical performance of a new device for measurement of PaO2, PaCO2, and arterial pH. METHODS: Forty-six patients undergoing cardiopulmonary bypass were enrolled in this study. All patients had a continuous intra-arterial sensor (PB 3300) placed into the radial artery through a 20-gauge catheter. A total of 319 arterial blood gas and pH values were obtained for comparison with a conventional blood gas analyzer. The measurements were performed every 12 hrs after the initial in vitro calibration of the sensor for each patient. RESULTS: Measurements were made over a range of 12 to 192 hrs. The overall bias and precision determined by the two methods were 4.5 and 17.1 mmHg for PaO2; 4.5 and 6.2 mmHg for PaCO2; and 0.009 and 0.035 for pH, respectively. For the range of PO2 less than 150 mmHg, the bias and precision improved to 4.2 and 9.5 mmHg. The sensor-derived PCO2 value, PCO2 (IABG), increased significantly more than the conventional blood gas analysis value, PCO2(ABG), even within 72 hrs (2.8 and 4.1 mmHg). The relationship between the two measurements can be described as: PCO2(IABG)/PCO2(ABG) = 1 + 0.0026.t where t is the time period of use (in hours). By correcting the PCO2(IABG) value using this formula, the overall bias and precision of the values measured by two methods decreases to -0.4 and 3.6 mmHg. CONCLUSIONS: The PO2 and pH values derived from an intra-arterial blood gas monitoring system agreed well with the values measured by a conventional blood gas analyzer. However, the PCO2 value must be corrected due to an increase of drift, especially with extended use for more than 72 hours.

Blood Gas Analysis↗

In vivo fluoride profiles at different sites of buccal and lingual enamel surfaces obtained by enamel biopsy of human maxillary first permanent molars in young adults.

Twenty male volunteers, average age 24 years, participated in this study. Specimens were obtained by enamel biopsy using 5 microliters of 0.5 M HClO4 for 30 s. Using a regression curve, comparisons of fluoride concentrations were made at different depths. The fluoride concentrations (mean +/- SE) at a depth of 5 microns were highest in the distobuccal (1698 +/- 136), high in the mesiobuccal (1343 +/- 122), low in the distolingual (1119 +/- 107), and lowest in the mesiolingual sites (819 +/- 78). Of the interior enamels (> or = 10 microns in depth), the distobuccal site (1330 +/- 88 parts/10(6) F at 10 microns) had a higher-concentration than all other sites. The fluoride profiles were steepest to shallowest in the order: distobuccal, mesiobuccal, distolingual and mesiolingual. There were no correlations between the enamel fluoride concentrations and the fluoride concentration in parotid saliva. It was concluded that in vivo fluoride profiles of maxillary first molars reflect the wear of the tooth surface with age and the condition of dental plaque deposition, and, to some extent, the site-specific distribution of saliva between buccal and lingual surfaces.

Adult↗

Inhibitory effects of d-limonene on the development of colonic aberrant crypt foci induced by azoxymethane in F344 rats.

The modifying effect of the monoterpenoid d-limonene in drinking water on the development of azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) was investigated in male F344 rats. The effects of d-limonene intake on ornithine decarboxylase (ODC) activity and on the silver stained nucleolar organizer region protein (AgNOR) count in the colonic mucosa were also estimated. Animals were given 3 weeks s.c. injections of AOM (15 mg/kg body wt) to induce ACF. These rats were treated with or without 0.5% d-limonene in the drinking water, starting 1 week before the first dosing with AOM. All rats were killed 2 weeks after the last AOM injection, to measure the number of ACF, ODC activity and AgNOR count/nucleus in the colon. In rats given AOM and d-limonene the frequencies of ACF and aberrant crypts/colon, and aberrant crypts/focus were significantly decreased compared with those of rats given AOM alone (P < 0.01, P < 0.001 and P < 0.001 respectively). Number of AgNOR counts/nucleus of rats treated with AOM and d-limonene was significantly smaller than that of rats treated with AOM alone (P < 0.001). These results suggest that the monoterpenoid d-limonene might be a chemopreventive agent for colonic carcinogenesis in rats.

Animals↗

Reduction of 123I-iomazenil uptake in haemodynamically and metabolically impaired brain areas in patients with cerebrovascular disease.

Iomazenil is a specific ligand for central-type benzodiazepine receptors (BZR). In order to determine the clinical significance of the findings of 123I-iomazenil single photon emission tomography (SPET) in cerebrovascular disease (CVD), we compared the cerebral uptake of 123I-iomazenil with oxygen metabolism measured by positron emission tomography (PET). Depending on the severity of the haemodynamic and/or metabolic impairment based on our institutional criteria [a reduction of < 30.6 ml 100g-1 min-1 in cerebral blood flow (CBF) and an increase of > 0.52 in the oxygen extraction fraction (OEF)], the cortical areas were classified into four groups as follows: Group I, normal CBF and OEF; Group II, normal CBF and increased OEF; Group III, reduced CBF and normal OEF; Group IV, reduced CBF and increased OEF. Seven patients (mean age 65 +/- 7 years) with CVD underwent both PET and 123I-iomazenil SPET within 8 days. The ratios of the mean counts in 14 regions of interest in the cerebral cortices to those in the cerebellar cortices (R/C ratios) were compared with the cerebral metabolic rate of oxygen (CMRO2). The R/C ratios of Group IV were lower than those of Group I (P < 0.005). The R/C ratios correlated with CMRO2 in Group III (r = 0.577, P < 0.01) and in Group IV (r = 0.707, P < 0.005), but not in Groups I or II. These results suggests that reduced uptake in 123I-iomazenil SPET reflects oxidative hypometabolism causing neuronal damage in haemodynamically and metabolically impaired areas in patients with CVD. This information may be valuable when deciding therapeutic approaches.

Aged↗

Vasoreactive effect of acetazolamide as a function of time with sequential PET 15O-water measurement.

The accurate assessment of vascular flow reserve is crucial for the evaluation of risk among patients with cerebrovascular disease. In six patients with unilateral occlusion of the internal carotid artery and one patient with unilateral occlusion of the middle cerebral artery (mean +/- S.D. age = 68 +/- 3 years), we measured cerebral blood flow (CBF) after the administration of 940 MBq 15O-water using a remotely controlled power injector. Studies were performed at rest, after 10 min, and then 10, 20 and 30 min after the administration of 1 mg acetazolamide to evaluate the vasoreactive effect, as reflected by an increase in CBF. Sixteen regions of interest (ROIs) were drawn over the CBF images. These ROIs were as follows in each hemisphere: Area I, four areas in the cortical middle cerebral arterial territory (superior frontal, frontal, temporal and parietal areas); Area II, four areas of the deep middle cerebral and vertebral arterial territory (occipital area, basal ganglia, thalamus and cerebellum). Taking normalized resting CBF to be 100%, the mean CBF measured 10, 20 and 30 min post-injection using sequential positron emission tomography was as follows: Area I, 141.4 +/- 16.3, 127.7 +/- 15.3 and 128.2 +/- 17.4% for non-occluded sites and 116.3 +/- 22.8, 112.7 +/- 16.4 and 114.9 +/- 17.1% for occluded sites; Area II, 143.4 +/- 14.5, 126.2 +/- 10.4 and 125.0 +/- 12.9% for non-occluded sites and 141.9 +/- 28.9, 126.0 +/- 20.5 and 124.1 +/- 17.1% for occluded sites. A significant difference in mean CBF was noted between the non-occluded and occluded sites in Area I, the most marked difference of 25.1% being observed 10 min after the administration of the acetazolamide. We conclude that for an accurate assessment of vascular reserve in patients with cerebrovascular disease, CBF should be measured 10 min post-administration of the acetazolamide.

Acetazolamide↗

Suppressing effects of 6-(2,5-dichlorophenyl)-2,4-diamino-1,3,5-triazine and related synthetic compounds on azoxymethane-induced aberrant crypt foci in rat colon.

The modifying effects of dietary administration of 6-(2,5-dichlorophenyl)-2,4-diamino-1,3,5-triazine and 5 related compounds on the occurrence of azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) were investigated in rats. Male F344 rats were given s.c. injections of AOM (15 mg/kg body weight) once a week for 3 weeks to induce ACF. They also received the diet containing 200 ppm test compound for 5 weeks, starting one week before the first dosing of AOM. At the termination of experiment, all of the compounds had caused a significant reduction in ACF frequency, which might be associated with suppression of the expression of proliferation biomarkers. The apoptotic index in the colonic mucosal epithelium of rats killed at 6 h after the first AOM exposure revealed no blocking activity of the compounds.

Animals↗

Early alterations of apoptosis and cell proliferation in azoxymethane-initiated rat colonic epithelium.

Alterations of apoptosis and cell proliferation in the colonic epithelium of rats after exposure to azoxymethane (AOM) were estimated by means of the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method, measurement of 5-bromo-2'-deoxyuridine (BrdU) incorporation, immunohistochemical staining for proliferating cell nuclear antigen (PCNA), and counting of mitotic cells. F344 male rats were given a single s.c. injection of AOM (15 mg/kg body weight) at 6 week of age, and killed 4 h, 8 h, 3 days, and 7 days after the AOM treatment. At 4 h after the treatment, many damaged cells were already observed in the colonic epithelium, and they were positive by TUNEL staining. At 8 h, the number of TUNEL-positive cells was largest. The reduction of DNA synthesis in the colonic epithelium, confirmed by BrdU incorporation, was not distinct in comparison with the mitotic inhibition. There was no remarkable change in PCNA labeling index, except that strong expression of PCNA was detected in many damaged cells. On the 3rd day, the appearance of cell death became infrequent and an increase of cell proliferation occurred. On the 7th day, the expression of TUNEL and the cell proliferation biomarkers were at almost normal levels. These findings suggest that AOM induces apoptosis, which is associated with synchronous inhibition of mitosis. The data also indicate that PCNA immunostaining does not reflect the true proliferation state in the early phase after AOM exposure, probably due to the occurrence of cell cycle arrest or DNA repair.

Animals↗

Heparin-coated circuits reduce the formation of TNF alpha during cardiopulmonary bypass.

BACKGROUND: Cardiopulmonary bypass (CPB) causes a systemic inflammatory response. TNF alpha, which is a major inflammatory mediator, has been found in the circulation during and after CPB. Although previous studies have shown that heparin coating of the extracorporeal circuits reduces complement and granulocyte activation, and the inflammatory response, the possible effect of heparin coating on TNF alpha formation and the inflammatory response has not been fully investigated. METHODS: Eighteen patients scheduled for coronary artery bypass grafting were divided randomly into two groups. One group of patients had extracorporeal perfusion using heparin coated circuits (HC group, n = 9). The other group had extra-corporeal perfusion using an identical circuit that was not coated (UC group, n = 9). Blood samples were drawn before, during, and after CPB for measurement of plasma TNF alpha, plasma IL-8, neutrophil count, and neutrophil elastase. RESULTS: Plasma levels of TNF alpha increased during CPB in the UC group but not in the HC group. Plasma concentrations of IL-8 increased similarly during and after CPB in both groups. Coating the circuits with heparin did not affect the levels of IL-8. In both groups, the neutrophil count increased after the release of the aortic cross clamp and remained elevated for three days. In the HC group, however, the increase of neutrophil count was significantly lower compared with the UC group. Plasma concentrations of neutrophil elastase were significantly increased during and after CPB in both groups. However, the levels of elastase were significantly lower at certain time points in the HC group. CONCLUSION: From these observations, we conclude that heparin coating of the extracorporeal circuits reduces the TNF alpha formation during CPB, which may reduce neutrophil activation.

Anticoagulants↗

Fast RARE MR imaging with variable flip angle excitation.

A method was developed for performing T1-weighted magnetic resonance imaging with the rapid acquisition with relaxation enhancement (RARE) sequence by altering the excitation flip angle. This method was called variable flip angle turbo spin-echo (VF-TSE) imaging. When the effective echo time corresponds to the first echo, the resolution worsens as the echo train length becomes longer. For this reason, the echo train length was set at three, the repetition time (TR) was shortened (100- 200 msec) to decrease imaging time, and the initial flip angle was adjusted (120 degrees-140 degrees) to improve image quality. Another advantage of this method is that the initial flip angle can be reduced to below 90 degrees when a longer TR is needed. Measured signal intensities for VF-TSE imaging matched theoretic predictions. VF-TSE imaging yielded high contrast-to-noise and signal-to-noise ratios without sacrificing resolution. The VF-TSE technique was useful for breath-hold, three-dimensional, and cardiac synchronization imaging.

Humans↗