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Biomedical subjects

H Fujiwara

Publications and source records attributed to H Fujiwara.

At least 163 records · Page 9Linked to original sources

Nonlinear ablation targeting an isthmus of critically slow conduction detected by high-density electroanatomical mapping for atypical atrial flutter.

Focused high-density atrial endocardial mapping was performed with a three-dimensional electroanatomical mapping system or a multielectrode basket catheter in six men and two women (mean age = 54 years) with atypical atrial flutter (AFL) to characterize its reentry circuit and identify its isthmus of critically slow conduction (ICSC). Activation mapping revealed figure-8 reentry with ICSC between a surgical atrial scars in three atypical AFLs following atriotomy, and between the crista terminalis (CT) and the inferior (IVC) or superior (SVC) vena cavae in atypical right atrial (RA) AFL in absence of prior atriotomy. Figure-8 double loop reentry was documented in one RA atypical AFL. ICSC was characterized by concealed entrainment with a post-pacing interval identical to the AFL cycle length, and a mid-diastolic fractionated electrogram, 129 +/- 23 ms in duration, spanning the isoelectric line between double potentials on adjacent area of conduction block. All AFLs were successfully ablated with 4.9 +/- 4.3 RF pulses applied at ICSC. A possible mechanism of atypical AFL consists of figure-8 reentry with ICSC between surgical scars in postoperative AFL, and between the CT and the IVC/SVC in RA AFL not preceded by cardiac surgery. Late and partial regeneration of conduction across the atriotomy scar can create an ICSC. Nonlinear ablation targeting ICSC can cure atypical AFL, whether it follows surgery or not.

Atrial Flutter↗

Convenient test for screening metallo-beta-lactamase-producing gram-negative bacteria by using thiol compounds.

A simple disk diffusion test was constructed for detection of IMP-1-type metallo-beta-lactamase-producing gram-negative bacteria. Two Kirby-Bauer disks containing ceftazidime (CAZ) and a filter disk containing a metallo-beta-lactamase inhibitor were used in this test. Several IMP-1 inhibitors such as thiol compounds including 2-mercaptopropionic acid, heavy metal salts, and EDTA were evaluated for this test. Two CAZ disks were placed on a Mueller-Hinton agar plate on which a bacterial suspension was spread according to the method recommended by the National Committee for Clinical Laboratory Standards. The distance between the disks was kept to about 4 to 5 cm, and a filter disk containing a metallo-beta-lactamase inhibitor was placed near one of the CAZ disks within a center-to-center distance of 1.0 to 2.5 cm. For IMP-1-producing strains, the growth-inhibitory zone between the two disks expanded, while no evident change in the shape of the growth-inhibitory zone was observed for CAZ-resistant strains producing serine beta-lactamases such as AmpC or SHV-12. As a result, 2 to 3 microliter of undiluted 2-mercaptopropionic acid or mercaptoacetic acid able to block IMP-1 activity gave the most reproducible and clearest results, and CAZ-resistant strains producing AmpC or extended-spectrum beta-lactamases were distinguishable from IMP-1 producers by this test. A similar observation was made with IMP-1-producing clinical isolates such as Serratia marcescens, Klebsiella pneumoniae, Escherichia coli, Enterobacter cloacae, Enterobacter aerogenes, Citrobacter freundii, Proteus vulgaris, Pseudomonas aeruginosa, Pseudomonas putida, Acinetobacter spp., and Alcaligenes xylosoxidans. The specificity and sensitivity of this test were comparable to those of PCR analysis using bla(IMP)-specific primers. Therefore, this convenient test would be valuable for daily use in clinical laboratories.

Bacterial Proteins↗

Apoptosis in microvascular endothelial cells of perfused rabbit lungs with acute hydrostatic edema.

We test the hypothesis that microvascular endothelial cells may undergo apoptosis in response to acute pulmonary venous hypertension. The isolated rabbit lungs were perfused in situ for 4 h with left atrial pressure of 0, 10, or 20 mmHg at a constant blood flow. Edema formation was monitored by lung weight gain. To assay for apoptosis, we performed agarose gel electrophoresis of DNA, in situ nick end labeling of DNA strand breaks, and electron microscopy. We also examined the levels of expression of Bcl-2, a suppressor of apoptosis, in microvascular endothelial cells using an immunohistochemical technique. In a vascular pressure-dependent fashion, we found apoptosis in endothelial cells of alveolar septal capillaries, as well as expression of Bcl-2 in arteriolar and venular endothelial cells. We conclude that acute pulmonary venous hypertension induces apoptosis in capillary endothelial cells but not in arteriolar and venular endothelial cells, suggesting that microvascular endothelial cell apoptosis is dependent on the levels of Bcl-2 expression and influences the formation or resolution of acute hydrostatic lung edema.

Acute Disease↗

Epoxide hydrolase affects estrogen production in the human ovary.

To investigate the mechanisms of ovarian cell differentiation, we raised a new monoclonal antibody, HCL-3, which reacted with human luteal cells. It also reacted with human and porcine hepatocytes. The immunoaffinity-purified HCL-3 antigen from human corpora lutea (CL) was shown to be a 46-kDa protein. The N-terminal 22 amino acids of the 46-kDa protein from porcine liver exhibited high homology (82%) to human microsomal epoxide hydrolase (mEH). The purified HCL-3 antigen from human CL or porcine liver showed EH enzyme activity, confirming that HCL-3 antigen is identical to mEH, which is reported to detoxify the toxic substrates in the liver. In human follicles, mEH was immunohistochemically detected on granulosa and theca interna cells. In the menstrual and pregnant CL, mEH was also expressed on large and small luteal cells. A competitive inhibitor of EH, 1,2-epoxy-3,3,3-trichloropropane, inhibited the conversion of estradiol from testosterone by granulosa cells cultured in vitro, indicating the involvement of mEH in ovarian estrogen production. Because anticonvulsant sodium valproate and its analogues were reported to inhibit EH enzyme activity, these findings provide a new insight into the etiology of endocrine disorders that are frequently observed among epileptic patients taking anticonvulsant drugs.

Adolescent↗

Integrin binding specificity of laminin-10/11: laminin-10/11 are recognized by alpha 3 beta 1, alpha 6 beta 1 and alpha 6 beta 4 integrins.

Laminin-10/11, the laminin isoforms containing the alpha 5 chain, are major components of basement membranes of many fetal and adult tissues. Laminin-10/11 purified from the conditioned medium of human lung carcinoma cells were potent in mediating adhesion of the carcinoma cells in an integrin alpha 3 beta 1-dependent manner. To further define the type(s) of integrins involved in cell adhesion to laminin-10/11, we examined the effects of a panel of function-blocking anti-integrin antibodies on the adhesion of different cell types to laminin-10/11. Although anti-integrin beta 1 antibody inhibited the adhesion of all cell types tested, anti-alpha 3 antibody inhibited the adhesion of carcinoma and glioma cells but not fibroblastic cells. Adhesion of fibroblastic cells was inhibited, however, by a combination of anti-alpha 3 and anti-alpha 6 antibodies, suggesting that both alpha 3 beta 1 and alpha 6 beta 1 integrins function as laminin-10/11 receptors in these cells. To explore this possibility, we examined the adhesion of K562 leukemic cells transfected with integrin alpha 3 or alpha 6 subunit to laminin-10/11 or other laminin isoforms. Laminin-10/11 were potent adhesive ligands for both the alpha 3 beta 11 and alpha 6 beta 1 transfectants, whereas laminin-5 was the preferred ligand for the alpha 3 beta 1 transfectants. Upon stimulation with the activating anti-integrin beta 1 antibody, both transfectants became more adherent to the substratum regardless of the type of laminins coated, although their preference for laminin isoforms remained unaltered. K562 cells transfected with alpha 6 and beta 4 subunits were also capable of adhering to laminin-10/11, indicating that integrin alpha 6 beta 4 is another receptor for laminin-10/11. Even with lung carcinoma cells, the alpha 6-containing integrins partly contributed to adhesion to laminin-10/11 at higher coating concentrations, although non-integrin receptor(s) might also be involved under such conditions. These results indicated that laminin-10/11 are potent and versatile adhesive ligands in basement membranes capable of binding to both alpha 3 beta 1 and alpha 6 beta 1 integrins with high avidity and also to alpha 6 beta 4 integrin.

Antigens, CD↗

Synthesis of [1]benzopyrano[2,3,4-kl]acridin-3-ol and its analogues as pentacyclic compounds.

A new heterocyclic compound, [1]benzopyrano[2,3,4-kl]acridin-3-ol was synthesized by cyclization of xanthone derivatives. The key compound, 1-(3'-methoxyanilino)-xanthone, was prepared from 1-aminoxanthone. [1]benzopyrano[2,3,4-kl]acridin-3-ol analogues, [1]benzothiopyrano[2,3,4-kl]acridin-3-ol, pyrido[3',2':5,6]pyrano[2,3,4-kl]acridin-3-ol and pyrido[3',2':5,6]thiopyrano[2,3,4-kl]acridin-3-ol were synthesized by the same method.

Acridines↗

Heart disease in Friedreich's ataxia: observation of a case for half a century.

A case of Friedreich's ataxia was followed for 47 years, beginning in 1930; this patient had an abnormal electrocardiogram (flat or inverted T waves in leads II and III with prolonged QT interval) from the very beginning of the onset of neurological symptoms. Cardiac and neurological disturbances progressed slowly but steadily, and the patient died suddenly at the age of 67. The autopsy revealed typical findings of Friedreich's ataxia and hypertrophic cardiomyopathy with thickened left ventricular wall and myocardial fiber disarray. To the authors' knowledge, this is the longest continuous follow-up study of Friedreich's ataxia, and it will provide invaluable information on the natural history and development of the cardiac and neurological disorders in this condition.

Adult↗

A peculiar form of focal atrial tachycardia mimicking atypical atrial flutter.

A 55-year-old man was referred because of congestive heart failure and atrial flutter. A 12-lead electrocardiogram (ECG) showed positive P waves in leads II, III, and aVF with a continuously undulating pattern that lacked an isoelectric baseline. Tachycardia was diagnosed as atypical atrial flutter based on classical criteria. An electrophysiological study and catheter ablation using an electroanatomical system revealed the mechanism of the tachycardia to be focal atrial tachycardia originating from the left atrial roof. This case indicates that focal atrial tachycardia may present as atypical atrial flutter on the surface ECG.

Atrial Flutter↗

Risk of premature birth in multifetal pregnancy.

The risk of preterm delivery (< 37 weeks of gestation) is approximately nine times higher in women with multifetal pregnancies than in women with singleton pregnancies. However, it is possible that the risk will vary according to gestational week. To assess the risk of premature birth within 1 week by gestational age among multifetal pregnancies and compare the estimated risk with that of singleton pregnancies, we analyzed 6,036,475 infants born in singleton pregnancies and 90,887 infants born in multifetal pregnancies in Japan (> or =22 weeks) over the 5-year period 1989-1993. An estimate of the risk of birth within 1 week at gestational week n was obtained by dividing the number of infants delivered at gestational week n by the number of infants delivered at or beyond gestational week n. The risk at 22 weeks was 0.9 per 1000 fetuses for singleton pregnancies and 5.0 per 1000 for multifetal pregnancies. The risk remained relatively stable until 27 weeks of gestation, then sharply increased toward 36 weeks of gestation in both singleton and multifetal pregnancies. The odds ratio for birth within 1 week for fetuses of multifetal pregnancies compared with fetuses of singleton pregnancies was 5.9 (95% CI, 5.4-6.5) at 22 weeks of gestation, increasing gradually with increasing gestational age until 33 weeks of gestation (13.7; 95% CI, 13.1-14.2) but declining thereafter to 8.8 (95% CI, 8.6-8.9) at 36 weeks of gestation. Results of data analysis for each year of the 5-year period did not differ substantially.

Confidence Intervals↗

The development of peritumoral stroma required for IL-12 induced tumor regression depends on the T cell/IFN-gamma-involving host-tumor interaction.

T cell migration into tumor masses is a critical process in the scenario of IL-12-induced tumor regression. Our previous study showed that this depends on the development of peritumoral stroma prior to IL-12 therapy. The present study investigated the regulation of the development of peritumoral stroma in comparison with tumor-parenchymal stroma. In the OV-HM and CSA1M tumor models, tumor regression associated with T cell migration was induced following IL-12 treatment. Both OV-HM and CSA1M tumor masses growing in syngeneic mice developed peritumoral stroma before IL-12 treatment. However, peritumoral stroma was not observed in these two types of tumor masses generated in nude mice, T cell-depleted syngeneic mice, anti-IFN-gamma mAb-treated mice or IFN-gamma-deficient mice. In contrast, parenchymal stroma formation did not appear to be affected because tumors generated in these groups of mice exhibited rather higher growth rates than those of tumors in normal syngeneic mice. Importantly, the lack of peritumoral stroma in tumor masses was associated with the failure of T cells to migrate to these tumor masses: splenic T cells prepared from IL-12-treated tumor-bearing mice migrated into the corresponding tumor mass growing in untreated syngeneic recipient mice, whereas portions of the same donor cells failed to migrate into the above stroma-negative tumor masses. These results indicate that the development of peritumoral and parenchymal stroma is differentially regulated; there exist functional differences in the two types of stroma; and the formation of peritumoral stroma requires components of the host's immune system such as IFN-gamma and T cells.

Animals↗

Cardiac sympathetic denervation from the early stage of Parkinson's disease: clinical and experimental studies with radiolabeled MIBG.

UNLABELLED: Autonomic disorder is not infrequent in patients with akinetic-rigid syndromes, including idiopathic Parkinson's disease. In the advanced stage of Parkinson's disease, abnormal blood pressure responses, such as orthostatic hypotension and abnormal circadian blood pressure rhythm, may occur. Few cases of reduced 123I-metaiodobenzylguanidine (MIBG) accumulation in the heart or limbs of Parkinson's disease patients have been reported. However, whether reduced accumulation is caused by damage to the postganglionic sympathetic nervous system or by central autonomic failure corresponding to abnormalities in blood pressure regulation is unknown. METHODS: We evaluated sympathetic denervation in 32 Parkinson's disease patients using 123I-MIBG cardiac scintigraphy and compared the findings with those for autonomic dysfunction detected by orthostatic hypotension and diurnal blood pressure variation. Cardiac 125I-MIBG accumulation was also determined in an experimental model of Parkinson's disease using mice pretreated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). RESULTS: Cardiac 123I-MIBG accumulation 15 min after injection and 4 h after injection was markedly reduced in the Parkinson's disease patients (heart-to-mediastinum ratio: 1.58 +/- 0.37 and 1.33 +/- 0.28, respectively) compared with 7 healthy volunteers (2.42 +/- 0.27 and 2.60 +/- 0.15, respectively). This reduction was observed even at the earlier stages of physical activity or disease duration and also in patients with normal blood pressure response and variation, indicating that the marked decrease in cardiac 123I-MIBG accumulation may be a special feature of Parkinson's disease. Pretreatment with a total dose of 100 mg/kg MPTP, which is the standard dose used to destroy the dopaminergic neurons in models of Parkinson's disease, significantly reduced cardiac 125I-MIBG accumulation in C57BL/6 mice. Interestingly, the reduction of 125I-MIBG accumulation was still significant when MPTP was reduced to 5 mg/kg. These findings indicated that the postganglionic sympathetic nerves may be damaged by MPTP or unknown toxic substrates in experimental or human Parkinson's disease during the early stage, because dopaminergic neurons and sympathetic nerves are substantially similar in their plasma membrane transporters. CONCLUSION: Cardiac scintigraphy with 123I-MIBG may be used as a new imaging approach in the diagnosis and characterization of akinetic-rigid syndromes, especially Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

[Syndrome of inappropriate antidiuretic hormone secretion associated with meningeal infiltration of tumor cells and elevated interleukin-1 beta and interleukin-6 in cerebrospinal fluid of a patient with adult T-cell leukemia].

A 73-year-old man with acute adult T-cell leukemia (ATL) in remission was re-admitted to our hospital due to drowsiness, headache, and bilateral knee joint pain on May 17, 1998. On admission, examinations revealed decreased serum sodium concentration (112 mEq/l), low plasma osmotic pressure (259 mOsm/l), and elevated antidiuretic hormone(5.6 pg/ml). Cerebrospinal fluid examination showed an increased number of abnormal flower-like lymphocyte (951/microliter). Brain computed tomography and magnetic resonance imaging found no abnormality in the hypothalamus or pituitary gland. These findings yielded a diagnosis of syndrome of inappropriate antidiuretic hormone secretion (SIADH). Though ATL patients typically exhibit a variety of clinical symptoms, SIADH is rarely one of the complications. Further investigation showed that IL-1 beta and IL-6 concentrations were increased in spinal fluid but not in serum. Recently, it has been reported that exogeneous IL-6 is an inducer of ADH secretion, and that primary ATL cells and HTLV-I infected cell lines can produce IL-6. In this case, we speculated that IL-6 produced by ATL cells that infiltrated a cerebral lesion may have played an important role in the development of SIADH.

Aged↗

[Endomyocardial biopsy: procedure and pathology].

Endomyocardial biopsy is one of the examinations seeking for the etiologies of myocardial diseases, different from the others evaluating physiological or functional states. The biopsy is most powerful for monitoring rejection of the transplanted hearts and anthracycline-induced cardiotoxicity. It can make a differential diagnosis between myocardial diseases based on the specific histological findings. Although the method is well established, the indication should be carefully selected, and attentions should be paid to prevent the possible complications. Besides histological approaches at light and electron microscopic levels, biochemical, pharmacological and immunological approaches on the biopsies will promise further understanding of the pathophysiological mechanisms underlying cardiac diseases.

Arrhythmias, Cardiac↗

[Metallic stent placement for iliac artery occlusive disease].

Since 1991, we have performed stent placement for 35 iliac artery lesions in 31 patients. The etiologic diseases were atherosclerotic in 34 patients and traumatic dissection in one. The indications of placement were total occlusion in 3, late restenosis after angioplasty in 5, dissection in 5, and residual stenosis due to inadequate angioplasty in 21. We also performed direct stent placement for one traumatic dissection. The stents used were Wallstents in 10, Palmaz stents in 14, Strecker stents in 9, and Memotherm stents in 2 lesions. Follow-up was performed clinically or angiographically with measurement of the ankle/arm pressure index. Stent placement was successful in all cases, and relief or improvement of symptoms was achieved. The follow-up period ranged from 6-85 months (mean, 37.3 months). Late stent stenosis or occlusion occurred in 6 cases, among which 4 occluded lesions were successfully recanalized by thrombolytic therapy with angioplasty or second stent placement. In total, the primary patency rates were 88% and 77% at two and four years, respectively, while the secondary patency rates were 94% and 94%. In conclusion, metallic stent placement may offer extended application of intravascular treatment for iliac artery occlusive disease, and good long-term patency rates can be expected.

Adult↗

Antitumor effect of alpha-galactosylceramide (KRN7000) on spontaneous hepatic metastases requires endogenous interleukin 12 in the liver.

Hepatic metastasis is a major clinical problem in cancer treatment. We examined antitumor activity of alpha-galactosylceramide (KRN7000) on mice with spontaneous liver metastases of reticulum cell sarcoma M5076 tumor cells (spontaneous metastasis model). In this model, all mice that were s.c. challenged with one million tumor cells developed a solid s.c. mass by day 7 and died of hepatic metastases. In the current study, we administered 100 microg/kg of KRN7000 to the model mice on days 7, 11, and 15. This treatment suppressed the growth of established liver metastases and resulted in the prolongation of survival time. Fluorescence-activated cell sorter analysis of phenotypes of spleen cells, hepatic lymphocytes, and regional lymph node cells around the s.c. tumor revealed that CD3+NK1.1+ (NKT) cells increased in hepatic lymphocytes of the KRN7000-treated mice. Cytotoxic activity and IFN-gamma production of hepatic lymphocytes were augmented in comparison with those of spleen cells and regional LN cells. At the same time, interleukin (IL)-12 production of hepatic lymphocytes was markedly enhanced. Neutralization of IL-12 using a blocking monoclonal antibody diminished the prolonged survival time. These results showed that the in vivo antitumor effects of KRN7000 on spontaneous liver metastases were dependent on the endogenous IL-12 production, where NKT cells in the liver are suggested to be involved. Adjuvant immunotherapy using KRN7000 could be a promising modality for the prevention of postoperative liver metastases.

Adjuvants, Immunologic↗