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Biomedical subjects

Y Fukunaga

Publications and source records attributed to Y Fukunaga.

At least 55 records · Page 3Linked to original sources

Cavitary lung cancer with an aspergilloma-like shadow.

A 66-year-old man who complained of cough and haemoptysis had a cavitary lesion with the meniscus sign in the right lower lung field on his chest X-ray and CT scan. He had smoked 40 cigarettes daily, for about 46 years. Initially, he was diagnosed with aspergilloma and given an antifungal agent. After 2 months, the cavitary lesion showed a slight irregularity of the inner border. The walls were irregularly thickened and were surrounded by infiltrative densities compared with the previous chest radiograph. Enlargement of right hilar and mediastinal lymph nodes was also observed. The fungus ball-like shadow was fixed on the anterior wall of the cavity and its position was not altered with the patient's movements. These radiographic findings led to suspicion that the lesion might be malignant. Transbronchial lung biopsy of the cavity wall and CT guided needle aspiration biopsy of the fungus ball-like lesion were performed. Microscopic examination revealed a squamous-cell carcinoma in both the cavity wall and the fungus ball-like lesion. There was no evidence of fungal elements. In conclusion, the meniscus sign is most often associated with benign diseases such as aspergilloma, however, one should remember that carcinoma may be a cause.

Aged↗

Increased intensity of lung infiltrates at the side of lung cancer in patients with lung cancer associated with pulmonary fibrosis.

It has been reported that lung cancer is frequently associated with idiopathic pulmonary fibrosis (IPF). The purpose of this study was to compare the intensity of lung infiltrates between the side associated with lung cancer and the side without lung cancer. Twenty-three patients (24 lung cancers) with primary lung cancer associated with pulmonary fibrosis were retrospectively evaluated. Chest CT findings were evaluated by three expert radiologists using the intensity scores. In 16 of the 23 patients, it was possible to compare the intensity of lung infiltrates between both sides of the lungs. As a result, increased intensity at the side in which lung cancer developed was demonstrated in 12 of 16 patients (75%). In the remaining four patients, intensity of lung infiltrates was the same in both lungs. In operated patients as well as autopsied patients, it was possible to evaluate the pathological findings of lung tissues around cancer cells. This study clearly demonstrates that the intensity of lung infiltrates increased at the side in which lung cancer developed.

Adenocarcinoma↗

Clinical and immunological significance of neopterin measurement in cerebrospinal fluid in patients with febrile convulsions.

Neopterin is synthesized mainly by monocytes/macrophages and is considered to be a marker for activation of the cellular immune system. It has been reported that cerebrospinal fluid (CSF) neopterin levels are significantly higher in patients with bacterial meningitis than in those with aseptic meningitis or non-pleocytotic CSF. In this study levels of neopterin and interferon-gamma (IFN-gamma) were measured in children with non-pleocytotic CSF. The CSF neopterin levels were significantly higher in patients with typical febrile convulsions (FCs) (15.0 +/- 4.5 nmol/l) than in those with pyrexia without convulsions (6.5 +/- 2.7 nmol/l) or convulsions without pyrexia, namely, epilepsy (4.8 +/- 2.4 nmol/l). The CSF neopterin/serum neopterin ratio (C/S ratio) was also higher in patients with typical FCs (1.54 +/- 0.83) than in those with pyrexia without convulsions (0.32 +/- 0.18) or convulsions without pyrexia (0.77 +/- 0.28). Patients with prolonged FCs tended to have higher CSF neopterin levels than those with typical FCs. There was also a tendency for CSF IFN-gamma levels to be higher in patients with FCs than in those with pyrexia without convulsions or convulsions without pyrexia. The results of the present study suggest that some immune activation in the central nervous system (CNS) compartment may be related to the mechanisms of FCs.

Child, Preschool↗

Hypertension and insulin resistance: role of peroxisome proliferator-activated receptor gamma.

1. Insulin resistance has been highlighted as a common causal factor for hypertension, hyperlipidaemia, diabetes mellitus and obesity, all of which are recognized to occur simultaneously, and a distinct clinical entity is defined as 'multiple risk factor syndrome'. 2. Recently, a new class of antidiabetic agents, thiazolidinediones (TZD) has been developed and has been shown to improve insulin resistance by binding and activating a nuclear receptor, peroxisome proliferator-activated receptor (PPAR) gamma. 3. cDNA of rat PPAR gamma 1 and gamma 2 were cloned and gene regulation of PPAR gamma in rat mature adipocytes was examined. Hydrogen peroxide, an oxygen radical, which is recognized to be the common intracellular signal for multiple risk factors, potently down-regulated PPAR gamma mRNA expression in rat mature adipocytes. 4. Tumour necrosis factor (TNF)-alpha, which is considered to play a role in obesity-induced non-insulin-dependent diabetes mellitus and to augment oxidative stress, also suppressed PPAR gamma expression. 5. Thiazolidinediones dose-dependently recovered TNF-alpha-induced down-regulation of PPAR gamma mRNA expression. 6. The modulation of PPAR gamma expression by TZD can be one mechanism for the improvement of insulin resistance by TZD. 7. Vascular tone and remodelling are controlled by several vasoactive autocrine/paracrine factors produced by endothelial cells in response to several vascular injury stimuli, including hypertension. The PPAR gamma gene transcript was detected in cultured endothelial cells. 8. The administration of TZD stimulated the endothelial secretion of type-C natriuretic peptide, which is one of the natriuretic peptide family and is demonstrated by us to act as a novel endothelium-derived relaxing peptide. 9. Concomitantly, TZD significantly suppressed the secretion of endothelin, a potent endothelium-derived vasoconstricting peptide. 10. Thiazolidinediones can affect vascular tone and growth by modulating the production of endothelium-derived vasoactive substances to influence occurrence and progression of hypertension and atherosclerosis.

Adipose Tissue↗

New members of uncoupling protein family implicated in energy metabolism.

1. The regulation of energy metabolism involves food intake and energy expenditure. Mitochondrial uncoupling proteins (UCP) are implicated in energy expenditure. 2. cDNA of a homologue of UCP highly expressed in rat skeletal muscle, UCP-3, is isolated and sequenced. Rat UCP-2 cDNA is also isolated and sequenced. 3. Rat UCP-3 cDNA probe hybridized two bands, a major band at 2.5 kb and a minor band at 2.8 kb in rat tissues. The mRNA was expressed at the highest level in the skeletal muscle, and moderately in the interscapular brown adipose tissue (BAT). Only weak signals were detected in the epididymal white adipose tissue (WAT) and the heart. Rat UCP-2 cDNA probe hybridized a 1.7 kb band detected widely in the whole body, especially abundant in the lung and the spleen. In contrast to the UCP-3 gene expression, the UCP-2 gene expression was expressed at substantial levels in the WAT and only at slight levels in the skeletal muscle and BAT. 4. The UCP-3 gene expression is augmented two-fold in the gastrocnemius muscle from rats fed a high-fat diet (P < 0.05). The UCP-3 mRNA levels remained unchanged in the interscapular BAT, and epididymal WAT. The levels of the UCP-2 gene expression are augmented significantly in the epididymal WAT (1.6-fold; P < 0.05), while no significant increase is observed in the gastrocnemius muscle and interscapular BAT.

Adipose Tissue↗

Comparison of bioelectrical impedance analysis and dual energy X-ray absorptiometry for assessment of body composition in children.

BACKGROUND: There are a variety of methods for assessing body composition. Bioelectrical impedance analysis (BIA) is an easy and non-invasive technique, but has limitations in underweight and overweight subjects. Few reports have investigated the validity of BIA in children. In this report, the characteristics of BIA, especially in overweight and underweight children, are assessed and the results are compared with those of dual energy X-ray absorptiometry (DXA), as a reliable method for assessing body composition. METHODS: Determination of the fat-free mass (FFM), body fat content and percent body fat (%fat) was carried out using both BIA and DXA. The subjects (60 males and 44 females) were divided into five groups according to the percentage of ideal bodyweight (%IBW). Ten obese children, who were treated with exercise and a low-energy diet for 1 month, were also enrolled in this study. RESULTS: The %fat, FFM and body fat content showed a close correlation when measured by BIA and DXA with the correlation coefficients being 0.90, 0.95, and 0.95, respectively. In the underweight group, the %fat value determined by BIA tended to be greater than that determined by DXA, while in the overweight group, the BIA value was lower than the DXA value. The same trend was also seen in obese children before and after therapy with exercise and diet. CONCLUSION: Bioelectrical impedance analysis seems to be a reasonable method for daily clinical use, but attention should be paid to the interpretation of %fat values in underweight and overweight children.

Absorptiometry, Photon↗

Design and NMR analysis of HDV ribozymes for structural investigation.

Three variants of minimized hepatitis delta virus (HDV) RNA ribozyme systems (Rz-1 to approximately Rz-3) (Fig. 1) were designed on the basis of the "pseudoknot" structure model and synthesized. Rz-1 is a cis-acting ribozyme system (a cleaved form, 56-mer) in which stem IV is deleted from the active domain of genomic HDV RNA. Rz-1 was uniformly labeled with stable isotopes, 13C and 15N. The 2D-NOESY and 2D-HSQC data for Rz-1 suggest that Rz-1 forms the pseudoknot structure and G38 which is opposite to the cleavage site makes a base-pair. Rz-2 is a trans-acting ribozyme system which consists of three RNA oligomer strands (substrate: 8-mer, the cytidine residue at the cleavage site is replaced by 2'-O-methylcytidine; enzyme: 16-mer plus 35-mer). Rz-3 is a ribozyme in which the three RNA strands of Rz-2 are connected. It turns out that Rz-3 forms an inactive structure with low cleavage activity (k(obs) = 0.009) and final cleavage yield (6%). Rz-3 has the highest cleavage activity at pH 5.5. The optimal activity at acidic pH is similar to that of the wild type ribozyme. We also synthesized and examined the activity and structure of Rz-4 (designed by Perrotta and Been) which consists of two RNA strands (1).

Base Pairing↗

Nicotinamide inhibits sodium-dependent phosphate cotransport activity in rat small intestine.

BACKGROUND: We recently reported that the administration of niceritorol (a nicotinic acid derivative which improves lipid metabolism and peripheral circulation, and is used for the treatment of hyperlipidaemia and impaired peripheral circulation) to patients with hyperphosphataemia undergoing dialysis decreased the serum phosphate (Pi) concentration. We found that this was due to an acceleration of faecal Pi excretion by niceritrol. METHODS: Intestinal brush border membrane vesicles (BBMVs) were prepared from rat jejunum, and the Na+-dependent and Na+-independent Pi transport activities in these vesicles were measured. In addition, the functional Pi transporter from rat small intestine was injected in Xenopus oocytes, and the effect of nicotinamide on the levels of its expression were measured by northern blotting. RESULTS: The Na+-dependent component was significantly decreased in the BBMVs isolated from rats treated with nicotinamide, while the Na+-independent component was not changed. Kinetic studies demonstrated that the decreased activity was due to reduction of the Vmax value and not an elevation of the Km values. When poly(A)+RNA from rats treated with nicotinamide was microinjected into Xenopus oocytes, the Pi transport activity was significantly decreased compared with that in the control animals. In addition, there were no significant changes in Na/Pi cotransporters and activators, but the vitamin D receptor mRNA level was reduced to 80% of the control level. CONCLUSIONS: These observations suggest that nicotinamide may regulate the expression of a major functional Na/Pi cotransporter in the rat small intestine.

Animals↗

[Autoimmune fatigue syndrome and fibromyalgia syndrome].

We have encounted two patients with fibromyalgia (FM) initially diagnosed as having autoimmune fatigue syndrome (AIFS). To investigate the relationship between AIFS and FM, the distribution of the tender points in patients with AIFS was assessed according to the ACR criteria for FM. It was revealed that AIFS patients had 5.6 tender points on averages. Patients with headaches, digestive problems, or difficulty going to school had more tender points than patients without. Patients with ANA titers < 1: 160 had more tender points than patients with ANA > or = 1: 160. Anti-Sa negative patients had more tender points than positive patients. These results suggest a relationship between AIFS and FM in terms of the pathophysiologic mechanisms of the numerous tender points. In other words, ANA-positive FM patients could be one form of AIFS, as well as ANA-positive chronic fatigue syndrome patients. Thus, autoimmunity could explain the controversial disease entities of FM and/or CFS.

Adolescent↗

[A case of massive bloody stool caused by Meckel diverticulum in which 99mTc-HSA-DTPA SPECT was useful].

A 15-year-old boy was admitted to our hospital because of massive bloody stool. At the age of 11 years, he had two episodes of massive bloody stool, and 99mTcO4- Meckel scintigraphy failed to contribute to the diagnosis. On this admission, 99mTc-HSA-DTPA scintigraphy, especially coronal SPECT clearly showed bleeding site. Operation revealed Meckel diverticulum. We showed the usefulness of coronal SPECT in the evaluation of gastrointestinal bleeding.

Adolescent↗

Effect of neurotropin on the binding of high molecular weight kininogen and Hageman factor to human umbilical vein endothelial cells and the autoactivation of bound Hageman factor.

Bradykinin is generated by activation of the plasma kallikrein-kinin (K-K) cascade and contributes to the symptoms of allergic reactions and the perception of pain. Neurotropin is a biological material obtained from inflamed rabbit skin inoculated with vaccinia virus, which is widely used clinically in Japan as an effective agent for these disorders. Factor XII (FXII) and high molecular weight kininogen (HK), two critical constituents of the plasma K-K cascade, bind to endothelial cells, and bound FXII is autoactivated in the presence of zinc ions. We have investigated the effects of Neurotropin on the interactions of FXII and HK with endothelial cells. Neurotropin inhibited the binding of both proteins to cultured human umbilical vein endothelial cells (HUVEC) and inhibited autoactivation of FXII upon HUVEC in a concentration-dependent manner. These data suggest that the ameliorating effects of Neurotropin in allergic disorders and pain syndromes may be related to this ability to inhibit activation of the K-K cascade and, consequently, the formation of bradykinin.

Binding, Competitive↗

Cross polarization for 1H NMR image contrast in solids

A novel 1H imaging method for solids, yielding images reflecting 1H-13C dipolar interactions through cross relaxation time TIS, is presented. Phase-alternating multiple-contact cross polarization (PAMC CP) was incorporated into the magic-echo frequency-encoding imaging scheme; the PAMC CP sequence may partly but efficiently destroy the initial 1H magnetization depending on the TIS values. A theory describing the effects of the PAMC CP sequence was developed, which was used for the assessment of the sequence as well as the analysis for the experimental results. It was demonstrated that the TIS-weighted 1H image and the TIS mapping for a phantom, constituted of adamantane and ferrocene, can distinguish these compounds clearly. Copyright 1998 Academic Press.

Journal Article↗

[A surgical case for concomitant coronary artery disease and ASO with advanced colon cancer].

We report a successful surgical case of concomitant severe coronary artery disease and ASO with advanced sigmoid colon cancer. This patient underwent two-stage operation. Resection of the sigmoid colon was carried out first, then CABG and aortofemoral bypass was carried out simultaneously. The surgical strategy of a patient with coronary artery disease and malignant neoplasm is still controvertial, however, it should be decided considering the severity and the symptoms of both disease. In this case, ascending aorta was used as a donor artery for aortofemoral bypass. This technique will bring those benefits, i.e., consecutive operation procedures in same operating field, obtaining abundant blood flow to lower limb and safe IABP catheter insertion from subcutaneously tunneled bypass graft.

Adenocarcinoma↗

Time course of morphine withdrawal and preproenkephalin gene expression in the periaqueductal gray of rats.

We have previously reported the increase of preproenkephalin (PPE) mRNA in the caudal periaqueductal gray (PAG) of rats during morphine withdrawal. In this study, it was further evidenced that PPE mRNA in the caudal PAG was not increased by various kinds of stressor, suggesting that the increase in PPE mRNA in the caudal PAG is specific to morphine withdrawal. In order to investigate the physiological significance of the increase of PPE mRNA in the caudal PAG, we compared the time course of the increase of PPE mRNA in the caudal PAG with that of naloxone-precipitated or spontaneous morphine withdrawal signs. The increase of plasma corticosterone (PCS: 52 and 52 microg/100 ml; control group, 18 and 15 microg/100 ml) and body weight loss (-6 and -9%; control group, 0 and -1%) were observed but PPE mRNA increase was not detected 1 and 2 h after naloxone in morphine treated rats. PPE mRNA increased by 37 to 56%, while PCS elevation and body weight loss gradually diminished 4 h to 2 days after naloxone. A total of 12 h after spontaneous withdrawal, PCS was prominently increased (51 microg/100 ml; control group, 12 microg/100 ml), but body weight and PPE mRNA were not affected. One day after spontaneous withdrawal, PCS elevation (38 microg/100 ml; control group, 8 microg/100 ml) and body weight loss (-5%; control group, +3%) were observed and PPE mRNA also increased by 42%. Two to 3 days after the final morphine injection, PCS recovered to control level and body weight loss gradually disappeared, while PPE mRNA was still increased by 74 to 46%. These results suggest that PPE gene expression in the caudal PAG is stimulated in the recuperative phase of these morphine withdrawal signs.

Animals↗

Physiologic shear stress suppresses endothelin-converting enzyme-1 expression in vascular endothelial cells.

Shear stress dilates blood vessels and exerts an antiproliferative effect on vascular walls. These effects are ascribed to shear stress-induced, endothelium-derived vasoactive substances. Endothelin-converting enzymes (ECEs), the enzymes that convert big endothelin-1 (ET-1) to ET-1, have recently been isolated and the corresponding proteins have been termed ECE-1 and ECE-2. Furthermore, two isoforms of human ECE-1 have been demonstrated and termed ECE-1 alpha and ECE-1 beta. In this study, to elucidate the role of ECE-1 under shear stress we examined the effect of physiologic shear stress on the mRNA expression of ECE-1 and ET-1 in cultured bovine carotid artery endothelial cells (BAECs) and human umbilical veins (HUVECs), and also ECE-1 alpha mRNA expression in HUVECs. ECE-1 mRNA expression was significantly downregulated by shear stress in 24 h, both in BAECs and HUVECs, in a shear stress intensity-dependent manner. The expression of ECE-1 alpha mRNA was also attenuated by shear stress in HUVECs. ET-1 mRNA expression showed a concordant decrease with ECE-1 mRNA expression. These results suggest that shear stress-induced gene regulation of ET-1 and ECE-1 mRNA expression can contribute to the decrease of ET-1 peptide level by shear stress.

Animals↗

Oxidative stress suppresses the endothelial secretion of endothelin.

To address endothelial function on vascular walls exposed to oxidative stress, we investigated the effect of oxidative stress on the secretion of endothelin-1 (ET-1) from cultured bovine carotid artery endothelial cells (BAECs). Concentrations of ET-1 in the media were measured by a specific radioimmunoassay and ET-1 mRNA expression was estimated by Northern blot analysis. Treatment of BAECs with 0.5-2.0 mM H2O2 for 3 h suppressed both ET-1 secretion and ET-1 mRNA expression in a dose-dependent manner compared to control. Attenuation of ET-1 mRNA expression by H2O2 was revealed to take place at the transcriptional level. The addition of NG-nitro-L-arginine-methyl ester (L-NAME) 10 microns, a specific nitric oxide synthase inhibitor, had no effect on H2O2-induced suppression of ET-1 mRNA expression. Suppression of ET secretion under oxidative stress observed in the present study is proposed to be a compensatory mechanism of endothelial cells to inhibit vasoconstriction and proliferation during oxidative stress.

Animals↗

Effects of peptidase inhibitors, [D-Ala2, Met5]-enkephalinamide and antiserum to methionine-enkephalin microinjected into the caudal periaqueductal gray on morphine withdrawal in rats.

We examined the involvement of enkephalins in the caudal periaqueductal gray (cPAG) in morphine withdrawal in rats. Rats were treated with increasing doses of morphine (20-30 mg/kg/day, s.c., for 5 days) to develop morphine dependence. Morphine withdrawal was induced by naloxone (5 mg/kg, s.c.) 24 hr after the final morphine injection. The level of preproenkephalin (PPE) mRNA in the cPAG was estimated by quantitative in situ hybridization. PPE mRNA in the cPAG was increased 4-24 hr after naloxone in morphine-treated rats. A mixture of peptidase inhibitors (0.5 microl of a solution of amastatin, captopril and phosphoramidon, 3 x 10(-3) M each) microinjected into the cPAG suppressed morphine withdrawal (a decrease in the number of jumping, chin rubbing, paw rubbing and teeth chattering). Antiserum to methionine-enkephalin (1:10 dilution) microinjected into the cPAG did not significantly aggravate morphine withdrawal with or without the mixture of peptidase inhibitors. However, [D-Ala2, Met5]-enkephalinamide (20 nmol), an enkephalin analog, injected into the cPAG decreased the number of jumping without any influence on the other withdrawal signs. These results suggest that the increase in enkephalins in the cPAG may participate in the alleviation of morphine withdrawal (jumping behavior).

Animals↗

Enzyme-linked immunosorbent assay for serological survey of equine arteritis virus in racehorses.

To examine antibodies against equine arteritis virus (EAV), an enzyme-linked immunosorbent assay (ELISA) using purified virus antigen was developed. The results of ELISA were compared with those of serum neutralization (SN) tests. The ELISA absorbance values and the SN titers in sera collected weekly from EAV-infected horses showed a similar pattern. The ELISA could detect antibody to EAV in horses experimentally infected with not only a homologous virus strain, which was used as the ELISA antigen, but also a heterologous strain. Using the ELISA, serum samples collected in 1996 from racehorses in three prefectures (Hokkaido, Ibaraki, and Shiga) were examined and there was no evidence of recent EAV infection among these racehorse populations in Japan. The ELISA should be a simple and highly specific method for rapid screening of EAV infection in racehorses.

Animals↗