Search PubMed⌕ Search

Biomedical subjects

K Fujii

Publications and source records attributed to K Fujii.

At least 343 records · Page 19Linked to original sources
PubMed1997

Effect of aging on regulation of brain stem circulation during hypotension.

This study was designed to determine age related changes in autoregulatory responses of the brain stem circulation in vivo. In anesthetized adult (4 to 6 months, n = 8) and aged (24 to 26 months, n = 7) Sprague-Dawley rats, local CBF to the brain stem was determined with laser-Doppler flowmetry and diameters of the basilar artery and its branches were measured through an open cranial window during stepwise hemorrhagic hypotension. In aged rats, the lower limit of CBF autoregulation shifted upward to 60 to 75 mm Hg from 30 to 45 mm Hg in adult rats. Dilator responses of the basilar artery (baseline diameter: 254 +/- 15 microns), large branch (109 +/- 23 microns), and small branch (44 +/- 10 microns) to hypotension were much smaller in aged rats than in adult rats. The maximum change in diameter of the basilar artery during profound hypotension was significantly smaller in aged rats (11 +/- 8%) than that in adult ones (23 +/- 12%, P < 0.05); that of the large branch was 12 +/- 8% versus 33 +/- 17% (P < 0.005); and that of the small branch was 17 +/- 7% versus 40 +/- 13% (P < 0.0005), suggesting greater attenuation of the responses in the smaller vessels. Thus, this study provides direct evidence that aging diminishes the compensatory dilatation of brain stem arterioles and arteries during hypotension and modifies the autoregulatory plateau of CBF, which seems to increase the risk of the brain stem ischemia during hypotensive conditions.

Acetylcholine↗
PubMed1997

Role of nitric oxide in regulation of brain stem circulation during hypotension.

We tested the hypothesis that nitric oxide (NO) plays a role in CBF autoregulation in the brain stem during hypotension. In anesthetized rats, local CBF to the brain stem was determined with laser-Doppler flowmetry, and diameters of the basilar artery and its branches were measured through an open cranial window during stepwise hemorrhagic hypotension. During topical application of 10(-5) mol/L and 10(-4) mol/L N(omega)-nitro-L-arginine (L-NNA), a nonselective inhibitor of nitric oxide synthase (NOS), CBF started to decrease at higher steps of mean arterial blood pressure in proportion to the concentration of L-NNA in stepwise hypotension (45 to 60 mm Hg in the 10(-5) mol/L and 60 to 75 mm Hg in the 10(-4) mol/L L-NNA group versus 30 to 45 mm Hg in the control group). Dilator response of the basilar artery to severe hypotension was significantly attenuated by topical application of L-NNA (maximum dilatation at 30 mm Hg: 16 +/- 8% in the 10(-5) mol/L and 12 +/- 5% in the 10(-4) mol/L L-NNA group versus 34 +/- 4% in the control group), but that of the branches was similar between the control and L-NNA groups. Topical application of 10(-5) mol/L 7-nitro indazole, a selective inhibitor of neuronal NOS, did not affect changes in CBF or vessel diameter through the entire pressure range. Thus, endothelial but not neuronal NO seems to take part in the regulation of CBF to the the brain stem during hypotension around the lower limits of CBF autoregulation. The role of NO in mediating dilatation in response to hypotension appears to be greater in large arteries than in small ones.

Animals↗
PubMed1997

Association between hyperinsulinemia and intima-media thickness of the carotid artery in normotensive men.

OBJECTIVES: To determine whether hyperinsulinemia is associated with early atherosclerosis in normotensive men of a work site population. DESIGN AND METHODS: Six hundred and seventeen subjects were screened from 8678 male transport workers for the further examination of cardiovascular disease and diabetes. Subjects aged less than 40 years, those with hypertension or diabetes, or both, and those being administered medications for hyperlipidemia were excluded. Finally, 164 normotensive, nondiabetic subjects were enrolled. The intima-media thickness (IMT) was measured by B-mode ultrasonography with a 7.5 MHz probe. Electrocardiography, a 75 g oral glucose-tolerance test (OGTT) and blood chemistry measurements were also performed. The sum of insulin values (sigmaIRI) and the ratio of the sum of insulin values to blood glucose levels (sigmaIRI/sigmaBG) in the 75 g OGTT were used as markers of hyperinsulinemia. RESULTS: The mean age of the subjects was 52 +/- 5 years (mean +/- SD). In a univariate analysis, IMT was associated with age, systolic blood pressure, body mass index, sigmaIRI, and sigmaIRI/sigmaBG. Multivariate analysis showed that age, total cholesterol, and sigmaIRI (or sigmaIRI/sigmaBG) were independent risk factors for IMT. CONCLUSIONS: These results suggest that, in addition to age and total cholesterol, hyperinsulinemia as assessed by an OGTT is associated with early atherosclerosis in normotensive, nondiabetic men of a work site population.

Arteriosclerosis↗
PubMed1997

Mass effect caused by clinically unruptured cerebral arteriovenous malformations.

OBJECTIVE: It is generally considered that mass effect caused by arteriovenous malformations (AVMs) is evidence of ruptures. In the present study, the incidence of mass effect in clinically unruptured AVMs was evaluated, and the underlying causative factors and pathophysiological mechanisms were studied. METHODS: Twenty-seven patients with clinically unruptured supratentorial pial AVMs were examined. The majority were suffering from epilepsy, and frontal lobe involvement was revealed in approximately half of the patients. Angiographic studies, computed tomographic scans, and magnetic resonance images were obtained for all patients. Twenty-one patients underwent removal of AVMs. In 10 of the surgically treated patients, intraoperative vascular pressure measurements were obtained before removal of the AVMs. RESULTS: Mass effect was detected in 12 (44%) of the 27 patients. Cortical sulci obliteration (eight patients) and lateral ventricle displacement (seven patients) were frequently noted. The volume of AVMs was significantly larger in patients with mass effect than in those without mass effect (P < 0.001). Large dilated venous sacs or ectatic veins were observed to be associated with mass effect (P < 0.001). In only one patient was gross displacement related to a surrounding massive brain edema. Draining vein pressure in patients with mass effect was significantly elevated as compared to the average value in patients without mass effect (22 +/- 5 versus 12 +/- 3 mm Hg) (P < 0.01). CONCLUSION: The present study suggests that mass effect is not infrequent in clinically unruptured AVMs. Furthermore, multiple causative factors were detected, including the large size of AVMs, marked draining vein dilatation, and brain edema around the AVMs. Findings also indicated that a pathophysiologically high pressure in the venous drainage system may contribute to mass effect.

Adolescent↗
PubMed1997

An autopsy case of angioimmunoblastic T-cell lymphoma with a high content of epithelioid cells in the lymph node: immunohistochemical and genomic analyses.

A 79-year-old female developed red papulonodular eruptions on her extremities, facial erythema, generalized lymphadenopathy and high fever. Histopathology of an affected lymph node showed the features of angioimmunoblastic T-cell lymphoma with a high content of epithelioid cells. She died about two years after the onset despite therapy. Genomic Southern blotting and immunostaining of the lymph nodes were performed twice. In August of 1993, Southern blotting did not show any rearrangement of the immunoglobulin or the T-cell receptor (TCR) gene. Small or medium-sized lymphoid cells were positive for CD4 or CD8 (CD4:CD8 = 2:1). However, in September of 1994 (at autopsy), rearrangements of TCK C beta 1, J beta 2 and J gamma genes were observed. Small or medium-sized lymphoid cells were positive for CD4, but negative for CD8. Several large cells were positive for Latent Membrane Protein 1 (LMP1) of the Epstein-Barr virus (EBV). Our results proved that selective oligoclonal proliferation of tumor cells (probably CD4+) accompanied the disease progress.

Aged↗
PubMed1997

Differences in symptom structure between panic attack and limited symptom panic attack: a study using cluster analysis.

We had investigated the clinical characteristics of panic disorder (PD) in a Japanese outpatient population comprised of more than 250 patients diagnosed as having PD during a 13-year study period and observed that some PD patients had both panic attacks (PA) and limited symptom panic attacks (LPA). In the criteria for PD based on the Diagnostic and Statistics Manual of Mental Disorders, third edition-revised (DSM-III-R), episodes involving four or more symptoms are classified as PA, while those involving fewer than four symptoms are described as LPA. Therefore, LPA is identified as part of an episode of PA, since the difference between the two episodes is only in the number of symptoms. However, some recent research suggests that there is a distinct subgroup of individuals who suffer LPA. Using cluster analysis, we investigated the differences between PA and LPA groups in terms of the structures of several panic symptoms, which included anticipatory anxiety, agoraphobia and 13 clinical symptoms based on the DSM-III-R at the time of panic attacks, in 247 patients with PD. Cluster analysis revealed clusters of three and four panic symptoms in the PA group and LPA group, respectively, and there were also differences in symptom structure between the two groups. These results suggest that there may be a subgroup of individuals who show LPA among PD patients.

Adult↗
PubMed1997

Solitary esophageal metastasis of breast cancer with 15 years' latency: a case report and review of the literature.

A 68-year-old woman with a history of breast and colon cancer at the ages of 48 and 65 years, respectively, who presented with dysphagia is described. An upper gastrointestinal series and endoscopic examination revealed a circumferential stricture without ulceration in the middle-third area of the esophagus. Computed tomography demonstrated a submucosal tumor in the esophageal wall. A biopsy specimen obtained from the mucosa overlying the tumor revealed poorly differentiated adenocarcinoma, suggesting metastasis from the previous breast cancer. Subtotal esophagectomy with reconstruction was performed. Macroscopically, a submucosal tumor measuring 2.0 x 1.7 cm was observed in the resected esophagus. Microscopic examination revealed poorly differentiated adenocarcinoma, which was quite similar histologically to the breast cancer resected 15 years previously. Enzyme immunoassay and immunohistochemical analyses of the resected tumor revealed positivity for both estrogen and progesterone receptor, confirming the diagnosis of a metastatic cancer from the previous breast tumor.

Adenocarcinoma↗
PubMed1997

Tachykinin antagonist FK224 inhibits neurokinin A-, substance P- and capsaicin-induced human bronchial contraction.

To determine the roles of endogenously released tachykinins (substance P [SP] and neurokinin A [NKA]) in the human bronchial tissues, we studied the effects of tachykinin antagonist FK224 on bronchial smooth muscle contraction induced by SP, NKA and capsaicin in an organ bath. FK224 (10(-6) M and 10(-5) M, respectively) significantly inhibited NKA-induced contraction and 10(-5) M FK224 shifted the dose-response curve to more than one log unit higher concentration. Because SP- and capsaicin-induced contractions were small, we pretreated the tissues with the neutral endopeptidase inhibitor phosphoramidon (10(-5) M), which inhibits degradation of exogenous tachykinins in order to potentiate the contractions. FK224 (10(-5) M) significantly inhibited SP-induced contraction and it shifted the dose-response curves to about one log unit higher concentration. FK224 (10(-5) M) also significantly inhibited capsaicin-induced contraction and it shifted the dose-response curves to more than one log unit higher concentration. In contrast, FK224 (10(-5) M) did not affect on acetylcholine-, histamine-, and leukotriene D4-induced contraction. These results suggest that FK224 is a tachykinin receptor antagonist in the human bronchial smooth muscle, and that capsaicin-induced contraction is due to endogenously released tachykinin-like substances in the human bronchus.

Acetylcholine↗
PubMed1997

Effects of benzoxazinorifamycin KRM-1648 on cytokine production at sites of Mycobacterium avium complex infection induced in mice.

Although various antimicrobial agents exhibit appreciable microbicidal activity in the early phase (weeks 2 t0 4) of Mycobacterium avium complex (MAC) infection induced in mice, progressive bacterial regrowth subsequently occurs. To clarify the reason for this pattern of changes, we studied changes in the levels of various cytokines in tissue at sites of infection (spleens and lungs) of MAC-infected mice which were or were not given a benzoxazinorifamycin, KRM-1648 (KRM). Levels of the proinflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and gamma interferon (IFN-gamma) in tissues temporarily increased at around weeks 2 to 4 after infection, rapidly decreased thereafter, and returned to normal by week 8. Similar but somewhat delayed changes were noted for levels of interleukin 10 (IL-10) and transforming growth factor beta (TGF-beta), immunosuppressive cytokines with macrophage (M phi)-deactivating activity, in tissue, except that TGF-beta levels in the spleen remained high during weeks 4 to 8. KRM treatment blocked the increase in the levels of all of those cytokines in tissue in the early phase of infection, most strongly at week 4. IL-6 levels were beneath the limit of detection throughout the observation period. Bacterial loads in the visceral organs decreased during the first 2 weeks, and KRM treatment markedly promoted this decrease. However, regrowth of MAC organisms began at weeks 2 to 4 and continued thereafter, even in KRM-treated mice. Splenocytes and splenic M phi s of MAC-infected mice (week 2) produced and/or released into the culture fluid significant amounts of TNF-alpha (in a cell-bound form), IFN-gamma, and IL-10, but not TGF-beta, during 3 days of cultivation. A substantial amount of TGF-beta was produced during 2 weeks of cultivation of peritoneal M phi s. KRM itself did not significantly affect the IL-10- and TGF-beta-producing ability of cultured M phi s. These findings suggest that IL-10 and TGF-beta play important roles in the regrowth of MAC organisms seen during the course of KRM treatment.

Animals↗
PubMed1997

Clostridium septicum alpha-toxin is proteolytically activated by furin.

Clostridium septicum alpha-toxin is secreted as an inactive 46,450-Da protoxin. The protoxin is activated by proteolytic cleavage near the C terminus, which eventually causes the release of a 45-amino-acid fragment. Proteoytic activation and loss of the propeptide allow alpha-toxin to oligomerize and form pores on the plasma membrane, which results in colloidal-osmotic lysis. Activation may be accomplished in vitro by cleavage with trypsin at Arg367 (J. Ballard, Y. Sokolov, W. L. Yuan, B. L. Kagan, and R. K. Tweten, Mol. Microbiol. 10:627-634, 1993), which is located within the sequence KKRRGKR367S. A conspicuous feature of this site is a recognition site (RGKR) for the eukaryotic protease furin. Pro-alpha-toxin (AT[pro]) that was digested with trypsin or recombinant soluble furin yielded the 41,327-Da active form (AT[act]). A mutated alpha-toxin in which the furin consensus site was altered to KKRSGSRS at the cleavage site (AT[SGSR]) was cleaved and activated by trypsin but not by furin. In cytotoxicity assays, wild-type Chinese hamster ovary (CHO) and furin-deficient CHO (FD11) cells were killed by AT(pro) but not by AT(SGSR). Both cell types were killed by AT(SGSR) that was preactivated with trypsin. Propidium iodide uptake assays revealed that FD11 cells were approximately 22% less sensitive to AT(pro) than were CHO cells. AT(pro)-induced cell lysis of FD11 cells, assessed by propidium iodide uptake, was partially prevented by leupeptin (5 mM) and completely prevented by antipain (2.5 mM). The inhibition by antipain suggested the presence of cysteine or serine proteases that could also activate AT(pro). These findings demonstrate that furin is involved in the activation of C. septicum alpha-toxin on the cell surface but that alternate eukaryotic proteases can also activate the toxin. Regardless of the activating protease, the furin consensus site appears to be essential for the activation of alpha-toxin on the cell surface.

Animals↗
PubMed1997

Brain tumors: detection with C-11 choline PET.

PURPOSE: To evaluate the effectiveness of positron emission tomography (PET) with carbon-11 choline in brain tumor imaging. MATERIALS AND METHODS: A rat glioma cell line (C6) was incubated with C-14 choline; the time course of uptake and metabolism was determined in vitro. C-11 choline was injected intravenously in tumor-bearing rats; the time course of distribution in organs was determined. C-11 choline also was injected intravenously in 20 patients (aged 6-86 years) with brain tumors and two volunteers (aged 38 and 58 years); distribution of the tracer in the brain was determined. Regional cerebral blood flow was measured by using oxygen-15 water on the same day. RESULTS: C-14 choline was metabolized to phosphoryl choline in glioma cells. The uptake of C-11 choline by glioblastoma cells was three to four times higher than that in the rat brain. All brain tumors took up more C-11 choline than did normal brain; thus, brain tumors that were not treated, as well as those that were treated with surgery or radiation therapy, were depicted. The tumor-normal brain uptake ratio of C-11 choline in brain tumor did not correlate with the O-15 water regional blood flow in the corresponding area. CONCLUSION: C-11 choline PET can depict brain tumors effectively. This method was clinically useful in patients who had undergone surgery.

Adult↗
PubMed1997

Role of ATP-sensitive potassium channels in brain stem circulation during hypotension.

The basilar artery and its branch arterioles dilate actively in response to a marked decrease in blood pressure and maintain cerebral blood flow (CBF) to the brain stem. We tested the hypothesis that ATP-sensitive potassium (KATP) channels play a role in the autoregulatory responses of the brain stem circulation in vivo. In anesthetized Sprague-Dawley rats, local CBF to the brain stem was determined with laser-Doppler flowmetry, and diameters of the basilar artery and branch arterioles were measured through a cranial window during stepwise hemorrhagic hypotension. During topical application of 10(-6) and 10(-5) mol/l of glibenclamide, a selective KATP-channel blocker, the lower limit of CBF autoregulation shifted upward to 60-75 from 30-45 mmHg in the vehicle group. Glibenclamide significantly impaired the dilator response of small arterioles (baseline diameter 45 +/- 2 microns) throughout hypotension (P < 0.03) but did not impair the dilatation of the basilar artery (247 +/- 3 microns) or large arterioles (99 +/- 4 microns). Thus KATP channels appear to play an important role in the regulation of CBF to the the brain stem during hypotension by mediating the compensatory dilatation of small arterioles. In contrast, these channels may not be a major regulator of the vascular tone of larger arteries during hypotension.

ATP-Binding Cassette Transporters↗
PubMed1997

Esophageal stimulation by hydrochloric acid causes neurogenic inflammation in the airways in guinea pigs.

To investigate whether tachykinins are released in the airways in response to stimulation of the esophagus, we studied the airway plasma extravasation induced by intraesophageal HCl in the presence or absence of neutral endopeptidase inhibitor phosphoramidon and NK1-receptor antagonist FK-888 in anesthetized guinea pigs. The airway plasma leakage was evaluated by measuring extravasated Evans blue dye in the animals pretreated with propranolol and atropine. Infusion of 1 N HCl into the esophagus significantly increased plasma extravasation in the trachea. Phosphoramidon significantly potentiated plasma extravasation in the trachea and main bronchi, whereas FK-888 significantly inhibited that extravasation in a dose-related manner. In the capsaicin-treated animals, airway plasma extravasation was completely inhibited even in the presence of phosphoramidon. Tracheal plasma extravasation potentiated by phosphoramidon was significantly inhibited in the bilateral vagotomized animals. These results suggest that 1) tachykinin-like substances are released to cause plasma extravasation in the airways as a result of intraesophageal HCl stimulation and 2) there are neural pathways communicating between the esophagus and airways, including the vagus nerve.

Animals↗
PubMed1997

Evidence that allergen-induced contraction of guinea pig bronchi is mediated in part by the release of tachykinins.

To study the role of tachykinins in allergic responses in the airways of guinea pigs sensitized to ovalbumin (OVA), we examined the bronchial contractile response to allergen in the presence or absence of the tachykinin antagonist FK224 in vitro. Because neutral endopeptidase (NEP) effectively cleaves tachykinins, we incubated bronchial tissues with the NEP inhibitor phosphoramidon (10(-5) M) to maintain the activity of endogenously released tachykinins. Then we added 10(-5)% (10 microns/ml) OVA in the presence or absence of FK224 (10(-5) M). FK224 significantly inhibited OVA-induced contraction plateaued and began to relax, we added 10(-5) M phosphoramidon. In the tissue without FK224, phosphoramidon blocked the relaxation and enhanced the contraction. In contrast, in the tissues treated with FK224, phosphoramidon did not enhance the OVA-induced contraction. The enhancement of the contraction induced by phosphoramidon was not inhibited by the sodium channel blocker tetrodotoxin. These results suggest that (1) allergic response causes release of tachykinin-like substances to induce bronchial contraction in part, (2) these responses are blocked by tachykinin antagonist FK224 and (3) nerve conduction is not necessary for the release of tachykinin-like substances induced by allergic response in the guinea pig bronchus.

Allergens↗
PubMed1997

Intima-media thickness of the carotid artery in hypertensive subjects and hypertrophic cardiomyopathy patients.

While hypertension is known to cause left ventricular and vascular hypertrophy, the relationship between alterations of vascular and cardiac structures in patients with hypertrophic cardiomyopathy has not been fully clarified. We measured intima-media thickness of carotid arteries by ultrasonography in patients with hypertrophic cardiomyopathy (n = 16), normotensive subjects (n = 358), and hypertensive subjects (n = 386) in a cohort of 7940 male employees of a bus company. Our object was to determine whether vascular alteration occurs in hypertrophic cardiomyopathy similarly as in hypertension. Hypertrophic cardiomyopathy (wall thickness > or = 15 mm; asymmetrical hypertrophy without hypertension) was screened with family history and electrocardiography followed by echocardiography. The intima-media thickness in patients with hypertrophic cardiomyopathy (mean, 0.61 mm) did not differ from that of normotensive subjects (0.60 mm) but was significantly less than that of hypertensive subjects with left ventricular hypertrophy (wall thickness > or = 14 mm; n = 22; 0.73 mm). In a scatterplot of intima-media thickness versus interventricular septal thickness, these two parameters were significantly correlated in normotensives and hypertensives. The patients with hypertrophic cardiomyopathy distributed outside the 95% confidence range of the normotensive and hypertensive subjects. In summary, the increase in intima-media thickness of the carotid artery paralleled left ventricular hypertrophy in normotensive and hypertensive subjects. Patients with hypertrophic cardiomyopathy had a normal intima-media thickness regardless of the hypertrophied left ventricle. Thus, information on intima-media thickness may be useful in differentiating hypertensive left ventricular hypertrophy from hypertrophic cardiomyopathy.

Cardiomyopathy, Hypertrophic↗