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Biomedical subjects

M Fujimura

Publications and source records attributed to M Fujimura.

At least 145 records · Page 8Linked to original sources

Exacerbation of delayed cell injury after transient global ischemia in mutant mice with CuZn superoxide dismutase deficiency.

BACKGROUND AND PURPOSE: We have demonstrated that copper-zinc superoxide dismutase (CuZn-SOD), a cytosolic isoenzyme of SODs, has a protective role in the pathogenesis of superoxide radical-mediated brain injury. Using mice bearing a disruption of the CuZn-SOD gene (Sod1), the present study was designed to clarify the role of superoxide anion in the pathogenesis of selective vulnerability after transient global ischemia. METHODS: Sod1 knockout homozygous mutant mice (Sod1 -/-) with a complete absence of endogenous CuZn-SOD activity, heterozygous mutant mice (Sod1 +/-) with a 50% decrease in the activity, and littermate wild-type mice (male, 35 to 45 g) were subjected to global ischemia. Since the plasticity of the posterior communicating artery (PcomA) has been reported to influence the outcome of hippocampal injury, we assessed the relation between the plasticity of PcomAs and the decrease of regional cerebral blood flow in global ischemia. RESULTS: The fluorescence intensity of hydroethidine oxidation, a measurement of ethidium fluorescence for superoxide radicals, was increased in mutant mice 1 day after both 5 and 10 minutes of global ischemia, compared with wild-type mice. Hippocampal injury in the PcomA hypoplastic brains showed significant exacerbation in mutant mice compared with wild-type littermates 3 days after 5 minutes of global ischemia, although a marked difference was not observed at 1 day. CONCLUSIONS: These data suggest that superoxide radicals play an important role in the pathogenesis of delayed injury in the vulnerable hippocampal CA1 subregion after transient global ischemia.

Animals↗

Bronchodilator effect of inhaled olprinone, a phosphodiesterase 3 inhibitor, in asthmatic patients.

The effect of topical administration of phosphodiesterase (PDE) 3 inhibitors on the airway is not clear. In order to examine the usefulness of inhaled PDE3 inhibitors in the treatment of asthma, we investigated the bronchodilator effect of inhaled olprinone, a newly developed PDE3 inhibitor, in nine asthmatic patients. On three separate study days, olprinone, salbutamol, or vehicle was administered in a double-blind and randomized fashion, and pulmonary functions were assessed over 60 min. Significant increases in FEV(1) were observed until 45 min after inhalation of olprinone without adverse cardiovascular effects. Mean maximal increases in FEV(1) were 16.0 +/- 4.0 and 20.5 +/- 4.2% with olprinone and salbutamol, respectively. The bronchodilator effect of olprinone was greater than that of salbutamol in four of the nine patients. These results suggest that the inhaled PDE3 inhibitor has a bronchodilator effect in asthmatic patients.

Administration, Inhalation↗

Effect of leukotriene and thromboxane antagonist on propranolol-induced bronchoconstriction.

beta-adrenoreceptor blockers such as propranolol provoke bronchoconstriction only in asthmatic patients. Although cysteinyl leukotrienes (cLTs) and thromboxane A2 (TXA2) have been proposed to be involved in the pathophysiology of asthma, the role of these lipid mediators in propranolol-induced bronchoconstriction (PIB) has not been evaluated in asthmatics. This study was conducted to elucidate it. Nine patients with stable asthma, in whom a 20% or more decrease in FEV(1) occurred by inhalation of 20 mg/ml or less propranolol, participated in this study. A cLT antagonist, pranlukast (225 mg twice a day), a TXA2 antagonist, seratrodast (80 mg once a day), and placebo were orally given for 2 wk in a randomized and double-blinded manner. The provocative concentration of propranolol causing a 20% fall in FEV(1) (PC(20)) was determined on the last day of each 2-wk treatment. Pranlukast, but not seratrodast, tented to increase FEV(1) compared with placebo (2.14 +/- 0.29 versus 1.99 +/- 0.34 L, p = 0.0543). Pranlukast or seratrodast did not affect the PC(20) in comparison with placebo. We conclude that cLTs or TXA2 are not involved in PIB of asthmatics.

Adrenergic beta-Antagonists↗

The effect of a tilting seat on back, lower back and legs during sitting work.

The purpose of this study was to examine the possible effects of a tilting seat on the back, lower back and legs. Ten healthy male subjects aged 22-28 performed word-processing operations while sitting on a chair for one hour under two different seating conditions: the rocking condition and the fixed condition. While the subjects were performing the task, measurements of lower leg swelling were taken using bioelectrical impedance plethysmography, and pain scores were recorded every five min for the neck, shoulders, back, lower back, hips and legs. Electromyograms (EMGs) of the back and lower back (at Th5-6, Th8-9, L1-2 and L3-4) were recorded every sec. In addition, the subjects were videotaped while using the rocking seat, in order to analyze the angle and frequency of seat tilting. At the end of the experiment, the subjects were asked to evaluate the two conditions with respect to localized fatigue and operational efficiency. There was no significant difference in lower leg swelling between the two conditions. EMGs were significantly different at Th5-6, Th8-9 and L1-2 between the two conditions. The rocking condition generated greater EMGs at Th5-6 and L1-2, whereas the fixed condition produced greater EMGs at Th8-9. The pain scores for the neck, shoulders, back and lower back were higher under the fixed condition, while those for the buttocks were higher under the rocking condition. The average tilting frequency was as low as 25.2 times per hour, with 15.6 times per hour for tilting angles ranging from 1 to 2 degrees, and 9.6 times per hour for tilting angles exceeding 2 degrees. As for the subjective evaluations of localized fatigue, seven of the ten subjects preferred the rocking condition, while two preferred the fixed condition and one subject had no preference. Thus, there was a significant difference in the subjective evaluations of the two chairs. These findings suggest that the rocking condition, in contrast to the fixed seating condition, reduced back and lower back pain as a result of its tilting capability. The results of EMGs suggest that the rocking condition reduced back and lower back pain by increasing the overall muscle activity of the back and lower back. The leg impedance measurements showed no effect of the rocking condition on the leg swelling, as compared with the fixed condition.

Adult↗

[Tricuspid valve replacement in a patient with idiopathic tricuspid regurgitation].

Tricuspid regurgitation is often seen but is rarely categorized as "idiopathic". A 66-year-old man suspected of idiopathic tricuspid regurgitation underwent tricuspid valve replacement. With right heart failure over twenty years, his CTR increased to eighty six (86) per cent. During operation, no abnormal findings were observed except for the dilated tricuspid valve ring. Then a stented porcine xenograft (Carpentier-Edwards 33 mm) was inserted in the tricuspid valve annulus. Seven years after replacement, he died. Autopsy demonstrated myocardial hypertrophy of the right ventricle and dilatation of the right heart, supporting the diagnosis of idiopathic tricuspid regurgitation.

Aged↗

Molecular cloning of a human cDNA for the 41-kDa phosphoribosylpyrophosphate synthetase-associated protein.

A human cDNA encoding 41-kDa phosphoribosylpyrophosphate (PRPP) synthetase (PRS)-associated protein (PAP41) was cloned from two expressed sequence tag (EST) clones having the nucleotide similarity of 61.5 and 70.0% to human PAP39 cDNA. The predicted open reading frame of 1107 base pairs (bp) has the nucleotide identity of 91.8% to rat PAP41 and encodes a protein of 369 amino acids with a calculated molecular weight (MW) of 40,925. The deduced amino acid sequence exhibits the 98.9% identity to rat PAP41 and 72.2, 50.6, and 50.0% identity with human PAP39, PRS I, and PRS II, respectively, but lacks the PRPP binding site. Southern blot analysis suggested that the PAP41 gene exists as a single copy in the human genome. The single PAP41 mRNA of about 2.1 kb was shown to be present in five human cell lines by Northern blot analysis.

Adenocarcinoma↗

Urocortin-like immunoreactivity in the substantia nigra, ventral tegmental area and Edinger-Westphal nucleus of rat.

Neurons showing intense urocortin-like immunoreactivity (Ucn-IR) were found immunohistochemically in the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA), as well as in Edinger-Westphal nucleus (E-W), in the rat brain. Almost all Ucn-immunoreactive neuronal cell bodies in the SNc and VTA showed immunoreactivity for tyrosine hydroxylase. Injection of a retrograde tracer, colloidal gold-labeled WGAapoHRP, into the cervical spinal cord resulted in labeling of some E-W neurons with Ucn-IR. These findings suggest that Ucn is located in the cell bodies of dopaminergic neurons, as well as in the cell bodies of E-W neurons sending axons to the spinal cord.

Animals↗

A new method for right ventricular endomyocardial biopsy via the femoral veins: a novel approach employing a right ventriculography catheter (Nishiya type).

We have devised a new method for right ventricular endomyocardial biopsy, in which the use of a right ventriculography catheter (Nishiya Type) allows us to ensure the introduction of a guiding sheath (Cordis, right-angled long sheath) to the apical portion of the right ventricle by way of the femoral vein. With this method, we have biopsied the endomyocardium in 52 patients during the last 4 years. In each case, it only took us several minutes to complete the biopsy procedure. Neither failed applications nor significant complications were seen. We believe that this technique provides a clinically beneficial means as it enables us to readily and safely achieve right ventricular endomyocardial biopsy.

Adolescent↗

Cough receptor sensitivity to capsaicin and tartaric acid in patients with Mycoplasma pneumonia.

There has been no detailed study of cough sensitivity during acute lower respiratory infection. The aim of this study was to clarify cough sensitivity in Mycoplasma pneumonia, which is a well known acute lower respiratory infection with persistent nonproductive cough. We examined cough sensitivity to inhaled capsaicin and tartaric acid in both the acute and the convalescent phases of Mycoplasma pneumonia, cell differentials in bronchoalveolar lavage fluid, and pathologic findings of transbronchoscopic bronchial biopsy specimens. Although dry cough was observed in all patients during Mycoplasma pneumonia, cough sensitivity in the acute phase [capsaicin: 19.8 (GSEM, 0.214) microM, tartaric acid: 0.26 (GSEM, 0.356) M] were not enhanced compared with those in both control subjects [capsaicin: 27.9 (GSEM, 1.24) microM, tartaric acid: 0.316 (GSEM, 0.079) M] and patients in the convalescent phase [capsaicin: 15.7 (GSEM, 0.219) microM, tartaric acid: 0.50 (GSEM, 0.326) M] when all symptoms including cough had disappeared. The percentage of lymphocytes and neutrophils in bronchoalveolar lavage fluid BALF was significantly greater than in the control subjects, and lymphocyte-dominant bronchitis was observed in biopsied specimens. We conclude that cough threshold to inhaled capsaicin or tartaric acid was not enhanced during acute Mycoplasma pneumonia with lymphocyte-predominant bronchitis. This is the first report examining cough sensitivity in patients with acute lower respiratory infection with pneumonia.

Adult↗

Phylogenic study of calcitonin gene-related peptide-immunoreactive structures in the pancreas.

The immunohistochemical localization of calcitonin gene-related peptide was examined, at both light and electron microscopic levels, in the pancreas of various vertebrates, including the eel, bullfrog, turtle, chicken, mouse, rat, guinea pig, dog, monkey, and human. Immunoreactive staining was observed in nerve fibers in every animal species examined, but positive endocrine cells were limited to the rat, monkey, and human. The density of the positive endocrine cells varied considerably among the three species (monkey > rat > human). Positive nerve fibers were distributed throughout the parenchyma, being particularly rich around pancreatic ducts, and near large or small blood vessels. In four species (eel, mouse, rat, and dog), positive nerve fibers formed a dense network in the islet region. There were positive varicose nerve fibers around exocrine cells. These fibers, varying in density in different species (relatively high in the eel, bullfrog, and rat), were sometimes adjacent to acinar cells. At the electron microscopic level, positive nerve terminals were often demonstrated in close apposition to the outer membrane of acinar cells. The eel pancreas revealed an exceptional pattern of staining in neuronal cell bodies that were scattered in the interlobular connective tissue. Despite these anatomical differences, the omnipresence of this peptide suggests its essential role(s) in the pancreas.

Animals↗

Small cell lung cancer accompanied by lactic acidosis and syndrome of inappropriate secretion of antidiuretic hormone.

Lactic acidosis is a rare complication in lung cancer. We report a case of lung cancer accompanied by both syndrome of inappropriate secretion of antidiuretic hormone (SIADH) and lactic acidosis. A 70-year-old man was referred to our hospital for examination of a left hilar mass shadow on a chest X-ray film. Small cell lung cancer (SCLC) was demonstrated by brushing the bronchial mucosa of the left lower lobe bronchus. His laboratory data showed SIADH and lactic acidosis that were probably due to SCLC. Fluid restriction improved SIADH, and combination chemotherapy for SCLC improved the lactic acidosis although the tumor size did not change.

Acidosis, Lactic↗

Bronchoalveolar lavage cell findings in three types of eosinophilic pneumonia: acute, chronic and drug-induced eosinophilic pneumonia.

There are clinically different types of eosinophilic pneumonia (EP) but no study to date has compared pulmonary inflammatory cells between different types of EP, such as acute eosinophilic pneumonia (AEP), chronic eosinophilic pneumonia (CEP) and drug-induced eosinophilic pneumonia (drug-EP). The present study compared bronchoalveolar lavage fluid (BALF) cell findings to elucidate whether the profiles of the pulmonary inflammatory cells were different among the three types of EP. Clinical records of 28 patients with EP, consisting of eight AEP patients, 10 CEP patients and 10 drug-EP patients, were examined retrospectively. The differential cell counts, the CD4+/CD8+ ratio of lymphocytes, the percentage of HLA-DR+ in CD4+ and CD8+ lymphocytes, and the mean number of nuclear segmentations in cosinophils in BALF were compared among the three types of EP. The numbers of total cells, lymphocytes, neutrophils and eosinophils in BALF from patients with AEP were increased compared with those from normal subjects, and patients with CEP and drug-EP. The CD4+/CD8+ ratio of the BALF lymphocytes in patients with AEP, which exceeded 1.0 in all patients, was significantly higher than that in normal subjects. The percentages of HLA-DR+ cells in CD8+ lymphocytes in BALF from patients with CEP were significantly higher than those from patients with AEP and drug-EP. There was no significant difference in the mean number of nuclear segmentations in eosinophils in BALF among the three types of EP. The BALF cell findings in patients with EP showed some characteristics in accordance with type of EP. It is suggested that pulmonary neutrophils and lymphocytes, rather than eosinophils, may be related to the pathogenesis of the different types of EP.

Acute Disease↗

A partial involvement of histamine in ultrasonically nebulized distilled water-induced bronchoconstriction in guinea-pigs.

1. Inhalation of ultrasonically nebulized distilled water (UNDW) can induce bronchoconstriction only in asthmatics, but mechanisms of the response are not well known. We recently reported a guinea-pig model of UNDW-induced bronchoconstriction (UNDW-IB) in which UNDW induces bronchoconstriction when UNDW is inhaled 20 min after a challenge with aerosolized ovalbumin (OA) in passively sensitized, anaesthetized and artificially ventilated guinea-pigs. 2. To elucidate the role of histamine in the UNDW-IB, we examined the effects of antihistamines, diphenhydramine hydrochloride (DH) and chlorpheniramine maleate (CP), and measured histamine content in bronchoalveolar lavage fluid (BALF) in the animal model. 3. DH in doses of 0.1, 1.0 and 10 mg kg(-1) and CP in doses of 0.01, 0.1 and 1.0 mg kg(-1) administered intravenously 15 min after the OA challenge partially reduced the UNDW-IB at 1 and 2 min after the UNDW inhalation in a dose-dependent manner. Histamine content in BALF recovered 10 min after the UNDW inhalation following the OA provocation was significantly increased compared with that after saline inhalation and before the UNDW inhalation following the OA challenge. 4. Intravenous atropine in a dose of 0.5 mg kg(-1) or inhaled disodium cromoglycate in concentrations of 1 and 10 mg ml(-1) did not alter the UNDW-IB. 5. These results suggest that histamine is involved in part in the UNDW-IB in our animal model.

Administration, Inhalation↗

Role of tachykinins in distilled water-induced bronchoconstriction in guinea-pigs.

BACKGROUND: An inhalation of ultrasonically nebulized distilled water (UNDW) induces bronchoconstriction only in asthmatics, but the mechanism underlying the response is not fully understood. We recently showed that bronchoconstriction occurs immediately after UNDW is inhaled 20min after an aerosolized antigen challenge in passively sensitized guinea-pigs. OBJECTIVE: This study was conducted to examine the role of tachykinins in this response. METHODS: Passively sensitized animals were anaesthetized and artificially ventilated, and changes in pressure at the airway opening (Pao) were measured as an overall index of airway narrowing. A tachykinin NK1 and NK2 dual receptor antagonist, FK224, and a tachykinin NK1 selective antagonist, FK888, were intravenously administered 15 min after the antigen challenge. The effects of capsaicin desensitization and a neutral endopeptidase inhibitor, phosphoramidon, were also examined. RESULTS: FK224 and FK888 significantly (P < 0.05 and P < 0.05, respectively) reduced the time course curve of the increase in Pao caused by UNDW inhalation in a dose-dependent manner. The percentage increase in Pao from the preantigen challenge value at 1 min after the UNDW inhalation was 267.4+/-17.1, 358.0+/-33.7 and 412.4+/-27.6% with 10 mg/kg of FK224, 1.0 mg/kg of FK224 and vehicle, respectively, (P<0.01 between 10 mg/kg of FK224 and vehicle) and the value was 254.4+/-48.5% with 10 mg/kg of FK888, 327.1+/-57.6% with 1.0 mg/kg of FK888 and 418.5+/-39.0% with vehicle, respectively (P < 0.05 between 10 mg/kg of FK888 and vehicle). The capsaicin desensitization, but not phosphoramidon, significantly reduced the UNDW-induced increase in Pao. CONCLUSION: These results suggest that tachykinins, at least substance P, are involved in a part of the UNDW-induced bronchoconstriction in our guinea-pig model.

Animals↗

Necrotizing bronchial aspergillosis as a cause of hemoptysis in sarcoidosis.

The case history is presented of a patient with recurrent massive hemoptysis caused by necrotizing bronchial aspergillosis associated with sarcoidosis. The involved segments (right IX and X) were resected for treatment of the life-threatening hemoptysis. Histologic examination of the resected specimen confirmed the diagnosis. Necrotizing bronchial aspergillosis is a rare variant form of invasive pulmonary aspergillosis and has not been described previously as a cause of hemoptysis in sarcoidosis.

Aspergillosis↗

Cytosolic redistribution of cytochrome c after transient focal cerebral ischemia in rats.

Recent in vitro cell-free studies have shown that cytochrome c release from mitochondria is a critical step in the apoptotic process. The present study examined the expression of cytochrome c protein after transient focal cerebral ischemia in rats, in which apoptosis was assumed to contribute to the expansion of the ischemic lesion. In situ labeling of DNA breaks in frozen sections after 90 minutes of middle cerebral artery (MCA) occlusion showed a significant number of striatal and cortical neurons, which were maximized at 24 hours after ischemia, exhibiting chromatin condensation, nuclear segmentation, and apoptotic bodies. Cytosolic localization of cytochrome c was detected immunohistochemically in the ischemic area as early as 4 hours after 90 minutes of MCA occlusion. Western blot analysis of the cytosolic fraction revealed a strong single 15-kDa band, characteristic of cytochrome c, only in the samples from the ischemic hemisphere. Western blot analysis of the mitochondrial fraction showed a significant amount of mitochondrial cytochrome c in nonischemic brain, which was decreased in ischemic brain 24 hours after ischemia. These results provide the first evidence that cytochrome c is being released from mitochondria to the cytosol after transient focal ischemia. Although further evaluation is necessary to elucidate its correlation with DNA fragmentation, our results suggest the possibility that cytochrome c release may play a role in DNA-damaged neuronal cell death after transient focal cerebral ischemia in rats.

Animals↗

Case report: intrahepatic portal-hepatic venous shunts associated with a huge pelvic leiomyoma.

We present a case of portal-systemic encephalopathy due to intrahepatic multiple portal-hepatic venous shunts. A 71-year-old woman was admitted to our hospital because of recurrent episodes of disturbed consciousness. She showed no clinical signs of portal hypertension. Liver function was normal, except for an indocyanine green retention rate of 34% at 15 min and blood ammonia level of 282 microg/dL. Portal venography revealed dilatation of the portal vein and multiple portal-hepatic venous shunts, and a liver biopsy specimen revealed almost normal liver. Further clinical examination revealed a huge pelvic tumour. At laparotomy, two dilated veins were seen to arise from the pelvic tumour with blood flow into the mesentery. The tumour was resected successfully and a histological diagnosis of leiomyoma was made. The blood ammonia concentration decreased to the normal range postoperatively. A follow-up portal venogram demonstrated decreased portal vein dilatation and minor portal-hepatic venous shunts, considered to be congenital in origin. It is concluded that hepatic encephalopathy was produced in this patient due to an excess portal blood flow from the huge pelvic leiomyoma via the mesentery, with portosystemic shunting through pre-existent (probably congenital) intrahepatic anastomoses.

Aged↗