Biomedical subjects

T Katagiri

Publications and source records attributed to T Katagiri.

At least 109 records · Page 6Linked to original sources

PubMed1998

Skeletal abnormalities in doubly heterozygous Bmp4 and Bmp7 mice.

Analysis of the skeletal phenotypes caused by the genetic inactivation of individual Bmps, along with the study of their expression patterns, suggest possible functional redundancy of these molecules. To investigate the effect on skeleton development of the combined absence of some Bmp genes expressed in the same areas, we have intercrossed heterozygous Bmp7 mice with Bmp2 +/-, Bmp4 +/-, or Bmp5 +/- animals. Bmp2/7 and Bmp5/7 double heterozygous animals do not present with any abnormalities. In contrast, Bmp4/7 double heterozygotes develop minor defects in two restricted areas of the skeleton, the rib cage, and the distal part of the limbs. In the ribs, Bmp4 and Bmp7 seem to act in the same pathway to assure proper guidance of mesenchymal condensations of the ribs extending toward the sternum. In the limbs, these molecules appear to play a similar role in controlling digit number, possibly through induction of apoptosis in the interdigital and anterior mesenchyme.

Animals↗

PubMed1998

Uncommon electrocardiographic changes corresponding to symptoms during recurrent pulmonary embolism as documented by computed tomography scans.

Electrocardiographic (ECG) findings of pulmonary embolism (PE) include S1Q3T3 pattern, right bundle-branch block, right-axis deviation, and T-wave inversion in medial precordial leads. We report other uncommon ECG changes associated with various symptoms during recurrent PE as documented by computed tomography (CT) scans in a single patients. An 83-year-old woman was admitted with PE secondary to deep venous thrombosis in the left leg. During episodes of chest pain, ECG showed QTc prolongation (480 ms) with new T-wave inversion in leads III, aVF, and V1-V3, and ST-segment depression in leads V5-V6. Despite adequate anticoagulant therapy, recurrent episodes of PE occurred in the hospital. When the patient experienced sudden chest tightness, ECG showed a new S-wave notch in lead V1 and clock-wise rotation with sinus tachycardia. She also experienced transient syncope with hypotension. At this time, ECG showed transient atrioventricular junctional rhythm followed by sinus arrest, and CT scan showed a new massive embolus in the main pulmonary trunk with right ventricular dilatation, as demonstrated by echocardiography. The mechanism responsible for QTc prolongation with ST-T changes, the S-wave notch in lead V1 with clockwise rotation, or atrioventricular junctional rhythm with sinus arrest during PE may be associated with myocardial ischemia, acute right ventricular overload, or vagal reflex, respectively.

Aged↗

PubMed1998

High proportion of missense mutations of the BRCA1 and BRCA2 genes in Japanese breast cancer families.

Mutations in either of two recently identified genes, BRCA1 and BRCA2, are thought to be responsible for approximately two-thirds of all cases of autosomal-dominantly inherited breast cancer. To examine the nature and frequency of BRCA1 and BRCA2 mutations in Japanese families exhibiting a high incidence of breast cancer, we screened 78 unrelated families in this category for mutations of these two genes. Examining the entire coding sequences as well as exon-intron boundaries of both genes by polymerase chain reaction (PCR) single-strand conformation polymorphism (SSCP) and multiplex-SSCP analysis, we identified possible disease-causing alterations in BRCA1 among affected members of 15 families and in BRCA2 in another 14 families. In 15 of those 29 families, the affected individuals carried missense mutations, although most germline mutations reported worldwide have been deletions or nonsense mutations. Our results, indicating that missense mutations of BRCA1 and BRCA2 tend to predominate over frameshifts or nonsense mutations in Japanese breast cancer families, will contribute significantly to an understanding of mammary tumorigenesis in Japan, and will be of vital importance for future genetic testing.

BRCA2 Protein↗

PubMed1998

Correlation between exercise-induced ischemic ST-segment depression and myocardial blood flow quantified by positron emission tomography.

BACKGROUND: Ischemic ST-segment depression (horizontal or downsloping) is the most common manifestation of exercise-induced myocardial ischemia. The mechanisms responsible for these types of ST-segment depression are largely unknown. We investigated the relation of these 2 types of exercise-induced ST-segment depression to changes in regional myocardial blood flow (RMBF) by using exercise positron emission tomography (PET). METHODS AND RESULTS: The RMBF was measured with nitrogen-13 ammonia PET both at rest and during low-level supine bicycle exercise in 27 patients with angiographically proven coronary artery disease and in 6 healthy volunteers. ST-segment depression was measured from the isoelectric PR segment 80 ms after the J point. Exercise-induced horizontal ST-segment depression > or =0.1 mV was observed in 9 patients and downsloping depression > or =0.1 mV was observed in 18 patients. Multivessel disease was more frequent and areas of exercise-induced ischemia were larger in patients with downsloping depression than in patients with horizontal depression (P < .02, P < .05). In patients with horizontal ST-segment depression, RMBF in ischemic areas and in surrounding areas increased by a similar amount (31%+/-29% and 32%+/-16%) with exercise. In patients with downsloping ST-segment depression, RMBF was unchanged or decreased in ischemic areas (10%+/-24%) but increased in surrounding areas (46%+/-27%) with exercise. In healthy volunteers, RMBF increased in all areas (56%+/-30%) with exercise. CONCLUSIONS: Compared with horizontal changes in ST-segment morphology, downsloping changes may better indicate severe ischemia and greater differences in the increase of blood flow with exercise in the ischemic myocardium and in the surrounding areas.

Adult↗

PubMed1998

Cellular localization of interleukin-5 expression in rectal carcinoma with eosinophilia.

Eosinophilia often occurs in malignant diseases. This report concerns a female patient aged 76 years, diagnosed with rectal carcinoma with eosinophilia. Sera were obtained at two different periods (at diagnosis and after the operation) for the evaluation of levels of interleukin-5 (IL-5). The serum IL-5 level increased to 264 pg/mL, and returned to an undetectable level after the operation. The serum at diagnosis enhanced the viability of normal eosinophils in vitro, and this activity was inhibited by antihuman IL-5 polyclonal antibody. Immunohistochemistry and in situ hybridization revealed that stromal eosinophils contained IL-5 protein and messenger RNA (mRNA), but no IL-5 transcripts were detected in eosinophils attached to carcinoma cells. In situ detection of apoptosis showed that several eosinophils attached to tumor cells underwent apoptosis and lost their eosinophil secreted cationic protein (ECP) and major basic protein (MBP). These results may suggest that activated eosinophils by IL-5 play an important role in host defense mechanisms, releasing their toxic granule proteins on adjoining tumor cells.

Adenocarcinoma↗

PubMed1998

Production of oxidative products of nitric oxide in infarcted human heart.

OBJECTIVES: We sought to assess whether oxidation products of nitric oxide (NO), nitrite (NO2-) and nitrate (NO3-), referred to as NOx, are released by the heart of patients after acute myocardial infarction (AMI) and whether NOx can be determined in peripheral blood of these patients. BACKGROUND: Previously we reported that in experimental myocardial infarction (rabbits) NOx is released mainly by inflammatory cells (macrophages) in the myocardium 3 days after onset of ischemia. NOx is formed in heart muscle from NO; NO originates through the activity of the inducible form of nitric oxide synthase (iNOS). METHODS: Eight patients with acute anterior MI and an equal number of controls were studied. Coronary venous blood was obtained by coronary sinus catheterization; NOx concentrations in coronary sinus, in arterial and peripheral venous plasma were measured. Left ventricular end-diastolic pressure was determined. Measurements were carried out 24, 48 and 72 h after onset of symptoms. The type and location of coronary arterial lesions were determined by coronary angiography. Plasma NO3- was reduced to NO2- by nitrate reductase before determination of NO2- concentration by chemiluminescence. RESULTS: The results provided evidence that in patients with acute anterior MI, the myocardial production of nitrite and nitrate (NOx) was increased, as well as the coronary arterial-venous difference. Increased NOx production by the infarcted heart accounted for the increase of NOx concentration in arterial and the peripheral venous plasma. The peak elevation of NOx occurred on days 2 and 3 after onset of the symptoms, suggesting that NOx production was at least in part the result of production of NO by inflammatory cells (macrophages) in the heart. CONCLUSIONS: The appearance of oxidative products of NO (NO2- and NO3-) in peripheral blood of patients with acute MI is the result of their increased release from infarcted heart during the inflammatory phase of myocardial ischemia. Further studies are needed to define the clinical value of these observations.

Aged↗

PubMed1998

Effects of nicorandil, a potassium channel opener, on idiopathic ventricular tachycardia.

OBJECTIVES: We assessed the effects of the adenosine triphosphate (ATP)-sensitive potassium channel opener, nicorandil, on ATP- and verapamil-responsive ventricular tachycardias (VTs). BACKGROUND: Adenosine- or ATP-sensitive VTs are thought to be due to a nonreentrant mechanism, presumably delayed afterdepolarization. We suggest that this potassium channel opener may suppress ATP- and verapamil-sensitive VTs. METHOD: The subjects included 13 patients with idiopathic VTs, 7 of whom had sustained VT and 6 of whom had nonsustained VT. We evaluated the effects of ATP, nicorandil and verapamil on VTs. RESULTS: Sustained VT: Verapamil had preventive effects on seven VTs. Four VTs were terminated by ATP, and of these, nicorandil terminated two and prevented exercise-induced VT in the two others. Three ATP-insensitive VTs, which were determined to be due to a reentry by an electrophysiologic study, were not terminated by nicorandil. Nonsustained VT: All six VTs were inhibited by ATP, and five of these were suppressed by nicorandil. Verapamil inhibited four of the five VTs. QT intervals and the corrected QT intervals were significantly shortened by nicorandil. CONCLUSIONS: Nicorandil suppresses ATP- and verapamil-responsive VTs. One of the mechanisms of suppression by nicorandil might be related to a reduction of calcium in the myocardium, because it reduces the action potential duration.

Adenosine Triphosphate↗

PubMed1998

Vitamin K2 selectively induces apoptosis of blastic cells in myelodysplastic syndrome: flow cytometric detection of apoptotic cells using APO2.7 monoclonal antibody.

We have previously reported that vitamin K2 (VK2) but not VK1 has a potent apoptosis-inducing effect on freshly isolated leukemia cells from patients with various types of leukemia. By multi-color flow cytometric analysis using monoclonal antibody (mAb), APO2.7, which detects mitochondrial 7A6 antigen specifically expressed by cells undergoing apoptosis, we further investigated the apoptosis-inducing effect of VK2 on minor populations of leukemic blast cells in bone marrow from patients with myelodysplastic syndrome (MDS) and overt myeloid leukemia (post-MDS AML). Limiting dilution of CD95 (anti-Fas) mAb-treated apoptotic Jurkat cells with nonapoptotic CTB-1 cells revealed that APO2.7-positive Jurkat cells were consistently detectable by flow cytometry when present at levels of at least 5% in the CTB-1 suspension. In patient samples the gating area for leukemic clone was determined using cell surface antigen-specific mAbs conjugated with either fluorescein isothionate (FITC) or phycoerythrin (PE) and subsequently the cells stained with phycoerythrin cyanine (PE-Cy5)-conjugated APO2.7 mAb were assessed within the gating area of the leukemic clone for monitoring apoptosis. Treatment of the bone marrow mononuclear cells with 3-10 microM of VK2 (menaquinone-3, -4 and -5) in vitro potently induced apoptosis of the leukemic blast cells as compared with the untreated control cells in all 15 MDS patients tested. This effect was more prominent on blastic cells than that on mature myeloid cells such as CD34-/CD33+ gated cells. In addition, VK2 performed much less effectively on CD3-positive lymphoid cells. In contrast to VK2, VK1 did not show apoptosis-inducing activity. These data suggest that VK2 may be used for treatment of patients with MDS in blastic transformation.

Antibodies, Monoclonal↗

PubMed1998

A gene encoding phosphatidylinositol-4-phosphate 5-kinase is induced by water stress and abscisic acid in Arabidopsis thaliana.

Phosphatidylinositol-4-phosphate 5-kinase (PIP5K) phosphorylates phosphatidylinositol-4-phosphate to produce phosphatidylinositol-4,5-bisphosphate as a precursor of two second messengers, inositol-1,4,5-triphosphate and diacylglycerol, and as a regulator of many cellular proteins involved in signal transduction and cytoskeletal organization. Despite PIP5K playing such an essential role in a number of physiological processes, much still remains to be made clear about its association with plants. Searching the Arabidopsis expression sequence tag database against already known yeast and mammalian PIP5K cDNAs, we identified two clones which partly encode the same Arabidopsis PIP5K and isolated a corresponding full-length cDNA encoding a protein that we designated AtPIP5K1. Recombinant AtPIP5K1 expressed in Escherichia coli possessed a PIP5K activity in vitro. Due to some structural and biochemical differences, AtPIP5K1 was not categorized as either a type I or type II PIP5K. The expression of the AtPIP5K1 mRNA was induced rapidly by treating Arabidopsis plants with drought, salt and abscisic acid, which suggests that AtPIP5K11 is involved in water-stress signal transduction. These data give evidence for a close link between phosphoinositide signaling cascades and water-stress responses in plants.

Abscisic Acid↗

PubMed1998

Multiplex mutation screening of the BRCA1 gene in 1000 Japanese breast cancers.

To detect BRCA1 mutations in Japanese breast cancer patients, we screened 1,000 unselected primary cancers for mutations in exon 11, which accounts for 61% of the entire BRCA1 coding sequence. Using a method based on multiplex single-strand conformational polymorphism (SSCP) analysis of multiple restriction fragments generated by restriction-enzyme digestion of amplified DNA, we identified eight mutations. All eight were germline mutations; four of them were non-sense mutations or small deletions resulting in premature stop codons, and the other four were missense mutations. The Japanese carriers of these mutant BRCA1 alleles had developed breast cancers at ages ranging from 45 to 62, five of them bilaterally.

Aged↗

PubMed1998

Postnatal developmental changes in NSE and NNE mRNA expression in the rat pineal gland: in situ hybridization histochemistry.

By in situ hybridization, neuron-specific enolase (NSE) and non-neuronal enolase (NNE) mRNAs were examined in the rat pineal gland at the postnatal developmental and adult stages. The distributions of hybridized signals were analyzed in comparison with immunohistochemical staining of synaptophysin (SYN), which is a marker for pinealocytes. In SYN-positive areas that were observed throughout postnatal developmental and adult stages, we detected both NSE and NNE signals, which increased simultaneously during early postnatal development and thereafter became stationary. Quantitative analysis revealed that NNE signals were 2- to 3-fold greater in number than NSE signals at any given stage. This predominant expression pattern of NNE differed from that in neurons, which usually showed both signals at similar levels and seemed to reflect the difference in physiological function from neurons. During the early postnatal stages, a cord-like arrangement of cells without distinct SYN staining was observed. This arrangement was the thickest at postnatal day 0 and became dispersed and thinner with development, showing a relationship with formation of vascularized connective tissue stroma. By in situ hybridization, many of the constituent cells showed weak NNE signals but no distinct NSE signals. However, some cells also showed weak NSE signals, suggesting heterogeneity of these cells. The characteristic NSE and NNE expression patterns in the pineal gland cells clarified in this study might provide a basis for further studies of the differentiation and function of the pineal gland.

Animals↗

PubMed1998

Cloning of TCFL5 encoding a novel human basic helix-loop-helix motif protein that is specifically expressed in primary spermatocytes at the pachytene stage.

We have isolated a novel human gene that is expressed specifically in primary spermatocytes in the testis. The cDNA contains an open reading frame of 1356 bp, encoding a 452-amino-acid protein that includes a basic Helix-Loop-Helix (bHLH) motif. The gene, which was mapped to chromosome region 20q13.3-->qter by fluorescence in situ hybridization, consists of six exons and spans approximately 24 kb of genomic DNA. Immunohistochemical staining located the gene product exclusively in cell nuclei of primary spermatocytes at the pachytene stage, but not in those at the leptonema stage. We named this gene TCFL5 (transcription factor-like 5, basic helix-loop-helix). The cell-type and stage-specific expression of TCFL5 indicates that this protein may function in a crucial role in spermatogenesis as a transcription factor by regulating cell proliferation or differentiation of cells through binding to a specific DNA sequence like other bHLH molecules.

Animals↗

PubMed1998

Hypertrophic cardiomyopathy with apical left ventricular aneurysm.

We report a case of hypertrophic cardiomyopathy (HCM) with apical left ventricular aneurysm, which is difficult to review because cases are so rare. A 54-year-old Japanese man was first found to have an electrocardiographic abnormality (T-wave inversion at rest) 19 years ago, and non-obstructive apical HCM without identifiable cause was diagnosed by echocardiography, left ventriculography, and clinical findings. After 19 years, he was admitted because of repeated episodes of palpitation and chest oppression at rest. Widespread left ventricular hypertrophy from the anteroseptal wall to the apex with an apical left ventricular aneurysm was detected by echocardiography, left ventriculography, and cardiac magnetic resonance imaging. Histologic examination of the hypertrophic apical myocardium surrounding the aneurysm showed that the myocardial tissue had been extensively replaced by fibrous tissue containing hypertrophic myocardial fibers, and uptakes of [123I]-metaiodobenzyl guanidine (MIBG) and [123I-] beta-methyliodophenyl pentadecanoic acid (BMIPP) in single-photon emission photography images were reduced despite high myocardial perfusion. On the other hand, histologic examination of the hypertrophic anterior wall revealed myocardial hypertrophy with disorganization; myocardial perfusion and the uptakes of MIBG and BMIPP were preserved. Abnormalities of myocardial fatty acid metabolism and sympathetic neuron activity with preserved perfusion flow and histologic changes such as fibrosis in the apical wall are indicative of apical myocardial injury or ischemia (infarction) without coronary artery stenosis; apical aneurysm may have occurred in severe apical HCM with cavity obliteration up to the midventricular level.

Cardiomyopathy, Hypertrophic↗

PubMed1998

Alterations in sarcoplasmic reticulum and angiotensin II type 1 receptor gene expression after myocardial infarction in rats.

The purpose of this study was to investigate the function of sarcoplasmic reticulum (SR) and the role of angiotensin II type 1 receptor (AT1) in ventricular remodeling in non-infarcted areas after myocardial infarction (MI). MI was produced in anesthetized Sprague-Dawley rats (10-12-weeks old) by ligation of the left anterior descending coronary artery. Four weeks after MI, hemodynamic measurements were performed. SR Ca2+-ATPase activity and mRNA (SERCA2a) and AT1 mRNA (AT1a, AT1b) were analyzed. Left ventricular end-diastolic pressure was higher and left ventricular dp/dt was significantly lower in the MI group. In non-infarcted areas in the MI group, myocardial transverse diameter was significantly greater and both Ca2+-ATPase activity in the SR and SERCA2a level decreased. The AT1a level was higher in non-infarcted areas than in controls, whereas the AT1b mRNA expression level was unchanged. These results suggest that, in the ventricular remodeling after MI, alterations in SR protein and its mRNA in non-infarcted myocardium help initiate heart failure and that Ca overload caused by the up-regulation of AT1a mRNA is an important cause of alteration in SR function.

Animals↗

PubMed1998

Long-term effects of pharmacological therapy for vasovagal syncope on the basis of reproducibility during head-up tilt testing.

The purpose of this study was to determine the efficacy of long-term pharmacological therapy selected on the basis of a head-up tilt test (HUT) in patients in whom reproducibility of the HUT response was demonstrable in the initial study. The HUT (80 degrees upright) was performed for 15 min with or without an infusion of isoproterenol (0.01-0.03 microgram/kg per min) in 54 patients with recurrent unexplained syncope. When vasovagal syncope was induced (positive response), the HUT was repeated to examine the test reproducibility. Vasovagal syncope was induced in 24 patients during HUT alone, and in 30 patients during the HUT with isoproterenol. Acute reproducibility was observed in 49/54 (91%) patients. In the tilt-positive patients, HUT was repeated after an intravenous administration of propranolol (0.1 mg/kg) or disopyramide (1 mg/kg) (acute test). Propranolol proved effective in 21 (80%) of 26 patients, and disopyramide in 13 (56%) of 23 patients. Thereafter, evaluation was done on the long-term clinical follow-up of the pharmacological intervention selected on the basis of the acute test in the 34 patients in whom the HUT could not induce vasovagal syncope after the oral administration of the pharmacological agent (propranolol 60 mg/day, disopyramide 300 mg/day). Thirty-two of 34 patients (94%) did not develop syncopal attacks during a 44 +/- 12-month period. Thus, in patients with unexplained syncope, HUT appears to have a high degree of acute reproducibility, and the acute drug response guided by HUT may be used to develop an effective long-term pharmacological therapy.

Administration, Oral↗

PubMed1998

Decreasing parasympathetic tone activity and proarrhythmic effect after radiofrequency catheter ablation--differences in ablation site.

Holter ECG was used to evaluate changes in heart rate variability (HRV), indicators of the autonomic nervous system, and arrhythmia before and after radiofrequency (RF) catheter ablation in patients with symptomatic supraventricular tachycardia. Ablation targets in 43 patients included the atrioventricular (AV) nodal pathway (AVNRT, n = 17), a right free wall accessory pathway (n = 10), a septal accessory pathway (n = 6), and a left free wall accessory pathway (n = 10). The High frequency component (0.15 - 0.40 Hz) or pNN50 of HRV analysis, indicating parasympathetic activity, significantly decreased immediately after RF ablation in the AVNRT and septal accessory pathway groups, but not in the right or left wall groups. In contrast, in all four groups, ventricular premature contractions (VPCs) significantly increased in most of the patients, and ventricular tachycardia occurred in a few of the patients immediately after RF ablation. There was no serious arrhythmia. These alterations in HRV analysis and arrhythmia returned to the control level after 1 week or more. VPCs after RF ablation did not consistently increase as a result of the reduced parasympathetic tone activity, but at the lesion near the conduction system, the increase in VPCs was inhibited by higher parasympathetic tone activity, because the parasympathetic nerve fibers and receptors were distributed in these lesions.

Adolescent↗

PubMed1998

Biochemical and ultrastructural evaluations of the effect of ischemic preconditioning on ischemic myocardial injury--role of the adenosine triphosphate-sensitive potassium channel.

The aim of this study was to clarify the role of the adenosine triphosphate (ATP)-sensitive potassium channel on the mechanism of ischemic preconditioning (IP). Thirty-five anesthetized dogs were divided into 5 groups: (1) Control (C), (2) IP, (3) intravenous infusion of nicorandil (Ni) prior to IP, (4) glibenclamide (G1) pretreated with IP (G1+IP), and (5) G1 pretreated with Ni (G1+Ni). All groups had 60 min ischemia followed by 60 min reperfusion, and were analyzed by biochemical and morphological procedures. At the end of the 60-min reperfusion, %segment shortening in C indicated paradoxical bulging. This value had significantly recovered in IP and Ni groups, but it was still negative in the G1+IP and G1+Ni groups. Ca++-ATPase activity of the sarcoplasmic reticulum (SR) was significantly decreased in C. In the IP and Ni groups, this activity was significantly maintained; however, in the G1+IP and G1+Ni groups it was similar to that in C. State 3 respiration of mitochondria showed similar changes in the SR. In the ultrastructural observations, severely damaged cells were not observed in the IP and Ni groups. These results indicated that an ATP-sensitive potassium channel opener enhanced the effects of IP and its blockade abolished these phenomena. It was conclude that the ATP-sensitive potassium channel may play a key role in the mechanism of IP.

Adenosine Triphosphate↗

PubMed1998

Slow ventricular tachycardia located in the epicardium of the left ventricular base and characterized by effects of adenosine triphosphate, nicorandil and verapamil.

A 31-year-old male with slow ventricular tachycardia (VT) developed a nonsustained VT with prolongation of the JT intervals after injection of contrast medium and saline into the marginal vein of the coronary sinus. The earliest activation site of the VT existed in the epicardium of the left ventricular base. Adenosine triphosphate prevented induction of VT and prolongation of JT intervals. Ventricular premature contractions showing the same morphology as the VT were also inhibited by nicorandil and verapamil. The mechanism of the VT was suggested to be abnormal automaticity due to an increase in the Ca++ current into cells after prolongation of the action potential duration induced by hypothermia.

Adenosine Triphosphate↗