PubMed Health⌕ Search

Biomedical subjects

T Fujii

Publications and source records attributed to T Fujii.

At least 541 records · Page 30Linked to original sources
PubMed1997

[Analysis of cases allowed to cease erythromycin therapy for diffuse panbronchiolitis--comparative study between patients with cessation of the therapy and patients continuing the therapy].

We investigated the effect of erythromycin (EM) in patients with diffuse panbronchiolitis (DPB) who were divided into 2 groups, the short term group with 8 patients who were treated for at least 2 years and the long term group with 7 patients who were treated for more than 3 years. Each mean value of %VC, FEV1.0, FEV1.0% and PaO2 two years after administration to these patients was improved than before administration of EM, with the exception of PaO2 in the long term group. There was no change in %VC, FEV1.0, FEV1.0% or PaO2 in each group between one year after the therapy and thereafter, with the exception of the fact that FEV1.0% in the short term group, except patients restarting EM therapy, 2 years after the therapy was significantly higher than in the long term group. One patient was readministered EM because of recurrence of DPB after cessation of EM therapy, whose %VC, FEV1.0 and PaO2, but not FEV1.0%, one year after the therapy were increased in those before the therapy. The Neutrophil proportion in the bronchoalveolar lavage (BAL) fluid in this patient was still high after the therapy (94.5%), while that in the patients with cessation of the therapy was improved to the level of less than 8%. Neutrophil proportion in BAL fluids in the patients with continuation of the therapy revealed a high or low level after the therapy. These results suggest that the patients, whose %VC, FEB1.0% and PaO2 were improved and whose proportion of neutrophils in BAL fluid reduced to a normal level compared with those before EM therapy, can be allowed to cease therapy after 2 years or more of EM therapy.

Adolescent↗
PubMed1997

Effect of aeration and unsaturated fatty acids on expression of the Saccharomyces cerevisiae alcohol acetyltransferase gene.

The reduction of acetate ester synthesis by aeration and the addition of unsaturated fatty acids to the medium has been reported to be the result of the reduction in alcohol acetyltransferase (AATase) activity induced by inhibition of this enzyme. However, regulation of the AATase gene ATF1 has not been reported. In this study, ATF1 gene expression was studied by Northern analysis, and the results showed that the ATF1 gene was repressed both by aeration and by unsaturated fatty acids. The results also showed that the reduction of AATase activity is closely related to the degree of repression of ATF1 mRNA, which suggested that the gene repression is the primary means of reducing AATase activity in vivo. Using the Escherichia coli lacZ gene as a reporter gene, it was shown that a 150-bp fragment of the 5' flanking sequence played a major role in the repression by aeration and unsaturated fatty acid addition.

Acetyltransferases↗
PubMed1997

Methotrexate treatment in patients with adult onset Still's disease--retrospective study of 13 Japanese cases.

OBJECTIVE: To evaluate methotrexate treatment in patients with active adult onset Still's disease (AOSD). METHODS: Methotrexate was initially given as a single weekly oral dose of 5 mg and adjusted individually afterwards in 13 patients with active AOSD. Symptoms and laboratory findings were investigated. RESULTS: Signs of AOSD activity disappeared (remission) in eight patients between 3 and 16 weeks after starting methotrexate. In these patients, significant improvements in C reactive protein, erythrocyte sedimentation rate, white blood count, and serum ferritin were observed at 8, 12, 14, and 16 weeks after starting methotrexate, respectively. In six of these eight patients, steroids or non-steroidal anti-inflammatory drugs could be reduced or discontinued. In four patients methotrexate was not effective despite 12 or 16 weeks of treatment, and one patient discontinued treatment after 2 weeks because of severe nausea. Five patients suffered from adverse reactions, including acute interstitial pneumonia (one patient) and liver toxicity (two patients). Five out of eight patients successfully treated with methotrexate were HLA-DR4 positive (four homozygotes), and all the unsuccessfully treated patients were DR2 positive. CONCLUSIONS: Methotrexate is useful for controlling disease activity in AOSD, not only for refractory patients but also for patients who have never taken steroids or for those with steroid associated toxicity. However, serious adverse reactions can occur, as with rheumatoid arthritis. It is important to determine the critical factors, such as the immunogenetic background, that are associated with response to methotrexate treatment.

Adult↗
PubMed1997

High frequency of K-ras mutations in human colorectal hyperplastic polyps.

BACKGROUND: Hyperplastic polyps are common benign colorectal polyps, and are thought to have little association with malignant tumours in the colorectum. However, several reports suggest that some hyperplastic polyps may develop into colorectal neoplasms. AIM: To clarify genetic alterations in colorectal hyperplastic polyps. METHODS: Twenty eight colorectal polyps having serrated components were resected from patients endoscopically. The K-ras gene mutations in codons 12 and 13 were analysed by PCR-RFLP. Intranuclear p53 protein was immunostained by the avidin-biotin complex method. RESULTS: A mutation of the K-ras gene was detected in nine (47%) of 19 hyperplastic polyps, and five (56%) of nine adenomas. p53 protein nuclear accumulation was detected immunohistochemically in two (22%) of nine adenomas, but not in any of the hyperplastic polyps. CONCLUSION: Some hyperplastic polyps may be true neoplastic lesions, and could be precursors of malignant neoplasia.

Adenoma↗
PubMed1997

PAMP is a novel inhibitor of the tachykinin release in the airway of guinea pigs.

Proadrenomedullin NH2-terminal 20 peptide (PAMP), a newly identified hypotensive peptide, may play physiological roles in airway and cardiovascular controls. This study was designed to determine the mechanism responsible for the bronchoprotective effects of PAMP on capsaicin-induced bron-choconstriction in anesthetized guinea pigs. PAMP (10(-8)-10(-6) M) significantly inhibited capsaicin-induced bronchoconstriction in a dose-dependent manner. The bronchoprotective effect of PAMP (10(-6) M) was as large as that of isoproterenol (10(-7) M) and lasted > 10 min. The concentration of immunoreactive substance P (SP) in bronchoalveolar lavage fluid after administration of capsaicin (4 x 10(-6) M) was 120 +/- 10 fmol/ml. PAMP significantly inhibited the release of immunoreactive SP in a dose-dependent manner (60 +/- 6 fmol/ml for (10(-6) M PAMP, P < 0.01; 84 +/- 6 fmol/ml for 10(-7) M PAMP, P < 0.01; and 95 +/- 6 fmol/ml for 10(-8) M PAMP, P < 0.05). PAMP (10(-6) M) did not significantly affect exogenous neurokinin A (NKA) or NKA + SP-induced bronchoconstriction, whereas isoproterenol (10(-7) M) significantly inhibited exogenous tachykinin-induced bronchoconstriction. These findings suggest that the bronchoprotective effects of PAMP are mainly due to inhibition of the release of tachykinins at airway C-fiber endings.

Adrenomedullin↗
PubMed1997

Pilot study of ofloxacin and interferon-alpha combination therapy for chronic hepatitis C without sustained response to initial interferon administration.

A controlled trial comparing combination therapy with ofloxacin (OFLX) and interferon (IFN) versus IFN monotherapy was conducted in patients with chronic hepatitis C who failed IFN therapy. Twenty patients were assigned randomly to two groups. Equal doses of recombinant IFN alpha-2b were administered to each group for 24 weeks. For the IFN plus OFLX group, OFLX was administered for 12 weeks at a daily dose of 600 mg. Levels of hepatitis C virus RNA declined significantly from the first month after the start of IFN treatment compared with those before administration in both groups. Serum alanine aminotransferase levels were significantly lower in the IFN plus OFLX group at two and six months after the start of treatment than levels in the IFN group. The fraction of subjects whose levels of serum ALT normalized was also higher in the IFN plus OFLX group. Larger clinical trials should be undertaken.

Adult↗
PubMed1997

Persisting childish behavior after bilateral thalamic infarcts.

We report a case with bilateral paramedian thalamic infarcts. The patient showed a dramatic personality change characterized by childish behavior and euphoria; which remained unchanged for 2 years after the onset. 'Vorbeireden' characterized by approximate answers was also observed. Anterograde amnesia had quite improved after 2 years, while retrograde amnesia for 1 year prior to the stroke onset and vertical gaze palsy remained unchanged. An MRI scan demonstrated bilateral medial thalamic and right midbrain infarcts without other lesions in the brain. A position emission tomography study showed that cerebral metabolic rate for glucose was markedly decreased in both thalami and in the cerebellum, and only slightly decreased in the parietal and occipital cortical regions. Cerebral metabolic rates of glucose in the frontal and temporal cortices were within normal range. The paramedian thalamic lesions per se may be responsible for the patient's personality change, 'Vorbeireden', and amnesia.

Adult↗
PubMed1997

Adenosine modulates endothelin-induced bronchoconstriction in guinea pig airway.

The present study was designed to determine whether endogenous and exogenous adenosine modulates endothelin (ET)-induced bronchoconstriction. Exogenous adenosine enhances ET-induced bronchoconstriction. Following pretreatment with adenosine deaminase and theophylline to eliminate or antagonize endogenous adenosine, ET-1-induced bronchoconstriction was significantly attenuated, but not that of ET-3. In conclusion, this is the first report of an enhancement of ET-induced bronchoconstriction of guinea pig airways by endogenous and exogenous adenosine. Our findings may be useful in designing specific adenosine receptor antagonists as therapeutic agents in the management of bronchial asthma.

Acetylcholine↗
PubMed1997

Hypertensive nephropathy and the gene for angiotensin-converting enzyme.

To investigate the genetic determinants for microalbuminuria, we studied an insertion (I)/deletion (D) polymorphism of the angiotensin-converting enzyme (ACE) gene, which influences the plasma ACE level, in 333 consecutive hypertensive patients and 113 normotensive control subjects. The urinary albumin excretion rate was calculated by using a 12-hour urine collection (mean for two consecutive nights from 7 PM to 7 AM) in all 333 hypertensive patients. The ACE D allele frequency did not differ significantly between the hypertensive patients and the normotensive control subjects (0.37 and 0.33, respectively). Among the hypertensive patients, nephropathy (microalbuminuria and albuminuria) was more common (P < .001) in those with the ACE DD genotype than in those with other genotypes. The D allele frequency in the nephropathy group was significantly higher than that in the normoalbuminuric group (0.45 versus 0.32, chi 2 = 10.8, P < .001). These results indicate that ACE I/D polymorphism is a genetic determinant for hypertensive renal disease in hypertensive patients. This polymorphism might be a confounding factor involved in the association between hypertensive nephropathy and cardiovascular events.

Aged↗
PubMed1997

Synergistic effect of nitric oxide and vasoactive intestinal peptide on bronchoprotection against histamine in anesthetized guinea pigs.

Vasoactive intestinal peptide (VIP) and nitric oxide (NO) are considered to be nonadrenergic, noncholinergic (NANC) inhibitory neurostransmitters in the airways. It seems likely that these neurotransmitters may be coreleased and act as functional antagonists against bronchoconstrictor stimuli. In the present study, we examined the synergistic effect of NO and VIP on bronchoprotection against histamine in anesthetized guinea pigs. The NO donor, S-nitroso-N-acetylpenicillamine (SNAP) significantly inhibited histamine-induced bronchoconstriction in a dose-dependent manner. VIP also inhibited histamine-induced bronchoconstriction in a dose-dependent manner, but this bronchoprotective effect was short-lived. Additionally, VIP (10(-9) M) had no significant bronchoprotective effect, but a subthreshold dose of SNAP (10(-7) M) significantly potentiated VIP (10(-9) M)-induced bronchoprotection against histamine. Moreover, SNAP (10(-7) M) significantly enhanced VIP (10(-7) M)-induced bronchoprotection for a longer period of time. On the other hand, VIP (10(-9) M) also significantly potentiated SNAP-induced bronchoprotection against histamine. In conclusion, combination therapy with NO donor and VIP receptor agonist may have important advantages in the treatment of bronchial asthma, and both NO and VIP may contribute in complementary fashion to the NANC-induced relaxant response in guinea pig airways.

Anesthesia↗
PubMed1997

Phase I-II study of irinotecan hydrochloride combined with cisplatin in patients with advanced gastric cancer.

PURPOSE: A dose-escalation study of irinotecan hydrochloride (CPT-11) combined with fixed-dose cisplatin was conducted to determine the maximum-tolerated dose (MTD), dose-limiting toxicities, and objective response rate in patients with advanced gastric cancer. PATIENTS AND METHODS: Twenty-four patients with or without prior chemotherapy were enrolled. All patients were assessable for toxicities and response. On day 1, CPT-11 was administered as a 90-minute intravenous (I.V.) infusion, which was followed 2 hours later by a 120-minute I.V. infusion of cisplatin 80 mg/m2. CPT-11 alone at the same dose was administered again on day 15. The treatment was repeated every 4 weeks until disease progression was observed. The initial dose of CPT-11 was 60 mg/m2, and was escalated in increments of 10 mg/m2 until severe or life-threatening toxicity was observed. RESULTS: The MTD of this combination was CPT-11 80 mg/m2. At this dose level, 16.7% of patients (two of 12) had leukopenia of less than 1,000/microL, 66.7% (eight of 12) had neutropenia of less than 500/microL, and 16.7% (two of 12) had severe diarrhea of grade 4 during the first course. The dose-limiting toxicity was neutropenia. Ten patients achieved a partial response (PR), and the overall response rate was 41.7% among 24 patients (95% confidence interval, 21.9% to 61.4%). CONCLUSION: The recommended dose and schedule is CPT-11 70 mg/m2 on days 1 and 15 and cisplatin 80 mg/m2 on day 1 every 4 weeks. This combination of CPT-11 and cisplatin, considered to be active against advanced gastric cancer with acceptable toxicity, should be further assessed in a phase II study.

Adult↗
PubMed1997

A peptide antagonist derived from platelet-derived growth factor induces histamine release from rat peritoneal mast cells.

A synthetic peptide (ANFLVWEIVRKKP) designed from the platelet-derived growth factor (PDGF) B-chain, which is known to act as a PDGF antagonist, induced histamine release from rat peritoneal mast cells. Maximal release by the peptide reached about 50% of the total histamine content in mast cells and half-maximal release occurred at 15 microM. The histamine release induced by the PDGF antagonist was required for the presence of Ca2+ in the medium. Treatment of kinase inhibitors (staurosporine and genistein) with mast cells before exposure to the PDGF antagonist inhibited the release to some extent, while calmodulin antagonists (W-7 and R24571) had little effect. The PDGF antagonist induced the secretion of actin from mast cells concurrently with histamine release, though it had no effect on the distribution of tubulin. These results suggest the possibility that PDGF and its agonists may stimulate and induce exocytosis of peritoneal mast cells.

Animals↗
PubMed1997

Effect of coronary risk factors on coronary angiographic morphology in patients with ischemic heart disease.

We investigated the effects of hypercholesterolemia, hypertension, and diabetes mellitus, which are major coronary risk factors, on the angiographic morphology of coronary artery lesions in 204 patients with previous myocardial infarction or stable-effort angina: 39 patients with hypercholesterolemia (serum total cholesterol > 240 mg/dl) without hypertension and diabetes, 51 patients with hypertension without diabetes and hypercholesterolemia, 24 patients with diabetes without hypertension and hypercholesterolemia, and 90 patients without any of these 3 risk factors (control). Patients without coronary artery lesions were excluded. The severity of coronary artery lesions is expressed as the Gensini score and the morphology is classified according to Rosch's classification. The distribution of coronary artery lesions did not differ significantly between the 4 groups. The Gensini score was significantly higher in the hypercholesterolemia group than in the other groups (p < 0.05). Short concentric lesions were more frequent in the hypercholesterolemia group than in the control group (p < 0.01), and tubular regular lesions were more frequent in the hypertension and diabetes groups than in the control group (p < 0.01). These results suggest that hypercholesterolemia has a greater influence on the severity of coronary artery lesions than does hypertension or diabetes, and that the progression of coronary atherosclerosis may differ among patients with these risk factors.

Adult↗
PubMed1997

Antihypertensive effect of repeatedly administered YM358, an angiotensin AT1-receptor antagonist, in stroke-prone spontaneously hypertensive rats.

YM358 2,7-diethyl-5-[[2'-(1H-tetrazole-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[ 1,5-b][1,2,4]-triazole potassium salt), a novel nonpeptide angiotensin AT1-receptor antagonist, was administered daily for 4 weeks to 24-week-old stroke-prone spontaneously hypertensive rats (SHRSP). Its effects on systolic, mean and diastolic arterial pressure (SAP, MAP and DAP), heart rate and locomotor activity were investigated by using radiotelemetry. A clear diurnal variation in blood pressure, heart rate and locomotor activity was observed in synchrony with the light cycle. YM358 at a daily oral dose of 10 or 30 mg/kg produced a reduction of blood pressure in a dose-dependent manner. Although a mild attenuation of the antihypertensive effect of YM358 was observed during the early stage of therapy, YM358 at 30 mg/kg per day produced a significant and consistent decrease in 24-hr MAP and DAP, and it prevented the further development of hypertension. YM358 did not affect either heart rate or locomotor activity or their diurnal variations. After the discontinuation of therapy with YM358, the blood pressure recovered promptly to the control level while there was no sign of a rebound increase in blood pressure. These results suggest that YM358 may be potentially useful for the treatment of hypertension.

Angiotensin Receptor Antagonists↗
PubMed1997

Low sensitivity of adrenal chromaffin cells to acetylcholine, neostigmine and oxotremorine in 21-day-old rats.

In the previous study, we have demonstrated that nicotine hardly induces catecholamine release from adrenal medulla of 21-day-old rats. The present study examined the responsiveness of the adrenal chromaffin cells to acetylcholine in vitro and neostigmine and oxotremorine in vivo in 21-day-old and 8-week-old rats. As assessed by electron microscopy, the number of the chromaffin granules was markedly decreased and the content of adrenaline in adrenals was diminished significantly by oxotremorine treatment in 8-week-old rats, whereas these changes did not occur in 21-day-old rats. Morphological changes of the adrenal chromaffin cells, with respect to exocytosis, were not observed in neostigmine-treated 21-day-old rats and acetylcholine-treated adrenal slices prepared from 21-day-old rats. Catecholamine release was hardly evoked by acetylcholine in these slices as judged by measuring the catecholamine content in the medium. These results indicate that the sensitivity of the chromaffin cells to these secretagogues in 21-day-old rats is very low when compared to that in young adult rats.

Acetylcholine↗
PubMed1997

Orientation of photosynthetic reaction center reconstituted in neutral and charged liposomes.

The photosynthetic reaction center from the photosynthetic bacterium Rhodobacter sphaeroides was reconstituted into neutral, positively charged, or negatively charged liposomes. About 70% of photosynthetic reaction centers were reconstituted in the proteoliposomes exposing their H-subunit outside with positively charged lipids while only 30-40% of them were in the same topological orientation with neutral or negatively charged lipids.

Cytochrome c Group↗