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Biomedical subjects

K Segawa

Publications and source records attributed to K Segawa.

At least 37 records · Page 2Linked to original sources
PubMed1998

Class IC antiarrhythmic drugs, flecainide and pilsicainide, produce ST segment elevation simulating inferior myocardial ischemia.

Flecainide and pilsicainide, Class IC antiarrhythmic drugs with slow kinetics, were administered to a 64-year-old man experiencing ventricular tachycardia. Both drugs suppressed the arrhythmia, but caused ST segment elevation in leads II, III, and aVF. No evidence of ischemic heart disease was detected. Withdrawal of the drugs eliminated the ST change. Because these drugs frequently are used to treat tachyarrhythmias in patients who may present with chest pain, this rare ECG manifestation of Class IC drugs should be recognized to avoid misdiagnosis of acute inferior myocardial infarction.

Anti-Arrhythmia Agents↗
PubMed1998

Cholesterol-lowering effects of psyllium seed associated with urea metabolism.

Twenty-eight mild hypercholesterolemic male and female adults were orally administered psyllium seed for 3 months. After psyllium treatment, the serum total cholesterol, low-density-lipoprotein-cholesterol and atherogenic index significantly decreased, but levels of high-density-lipoprotein-cholesterol, triglyceride and urea nitrogen did not. To determine the parameters associated with the cholesterol-lowering effect in the subjects' backgrounds, both biochemical and hematological parameters, we statistically examined the correlation between pretreatment parameters and the absolute change of total cholesterol level. The absolute change of total cholesterol level showed a direct correlation with the triglyceride level at pretreatment (r=0.41, P=0.03) and had an inverse correlation with urea nitrogen level (r=-0.46, P=0.01) but not with the total cholesterol level (r=-0.18). The change in urea nitrogen level had an inverse correlation with the urea nitrogen level itself at pretreatment (r=-0.82, P=7 x 10[-8]) and had a direct correlation with the triglyceride level (r=0.43, P=0.02). The change in triglyceride level had an inverse correlation with the urea nitrogen level (r=-0.48, P=0.008). Furthermore, the change in total cholesterol level had direct correlations with changes in the triglyceride level (r=0.56, P=0.002) and the urea nitrogen level (r=0.51, P=0.006), but these changes in triglyceride and urea nitrogen level did not correlate significantly. These findings suggest the close association of urea nitrogen and lipid metabolism in hyperlipidemia and psyllium seed treatment.

Adult↗
PubMed1998

Coronary artery-pulmonary artery fistula originating from three major coronary branches associated with exertional chest pain and tachycardia-dependent left bundle branch block.

A 49-year-old male was admitted to our hospital because of chest pain. The pain occurred simultaneously with tachycardia-dependent left bundle branch block (LBBB) during exercise-stress and atropine-stress electrocardiogram (ECG) and on 24-h ambulatory ECG monitoring. Myocardial perfusion and metabolic scintigraphy with Tl-201 and I-123 BMIPP, respectively, showed no evidence of ischemia. Coronary arteriography revealed no atherosclerotic lesions, but did show a fistula between three major coronary arteries and the main pulmonary artery. The left-to-right shunt was undetectably small. Administration of diltiazem and metoprolol suppressed LBBB by attenuating the heart rate response to exercise, and reduced the chest pain. Therefore we presume that the exertional chest pain was not caused by myocardial ischemia but by the tachycardia-dependent LBBB. Coronary artery-pulmonary artery fistula is the most common type of coronary artery fistulae found incidentally in adulthood. Involvement of three major coronary branches is, however, rare. The case is discussed with a review of the literature.

Bundle-Branch Block↗
PubMed1998

[Value of MR cholangiography in the diagnosis of pancreatic diseases compared with endoscopic retrograde cholangiopancreatography].

PURPOSE: To compare magnetic resonance cholangiography (MRCP) with endoscopic retrograde cholangiography (ERCP) in the diagnosis of pancreatic diseases. METHODS: The authors retrospectively reviewed MRCP and ERCP images obtained in 56 patients with pancreatic diseases and 192 controls. Detectability of the pancreatic duct and its branches and diagnostic usefullness were evaluated. RESULTS: MRCP was successful in almost all the patients without ascitic fluid or ileus. Findings of the main pancreatic ducts (i.e., dilation, stenosis and obstruction) were similarly demonstrated by ERCP and MRCP. The degree of ductal narrowing tends to be overestimated with MRCP. CONCLUSION: MRCP appears to be less invasive than ERCP. MRCP could provide sufficient information and play a complementary role in the diagnosis of pancreatic diseases.

Adult↗
PubMed1997

Increased expression of highly branched N-glycans at cell surface is correlated with the malignant phenotypes of mouse tumor cells.

Three NIH3T3 transformants, MTAg, MTPy, and MT1, which grow similarly in soft agar media, showed remarkable differences in athymic mice: MTAg grew more rapidly than MTPy, whereas MT1 and NIH3T3 did not, and only MTAg metastasized in lung. Structural analysis of N-glycans from plasma membrane glycoproteins revealed that each sample contains similar amounts of N-glycans, but the relative amounts of 2,6-branched tri- and tetra-antennary oligosaccharides prominently increase and the relative amounts of biantennary oligosaccharides prominently decrease in the order of NIH3T3, MT1, MTPy, and MTAg, whereas those of others remained constant. Western blot analysis revealed that binding of Datura stramonium agglutinin, which interacts with 2,6-branched tri- and tetra-antennary oligosaccharides, is significantly increased in several bands from MTAg compared with NIH3T3, two of which are tentatively identified as lysosome-associated membrane protein-1 and fibronectin (FN)-receptor. It was also shown that the spreading of MTAg on FN-coated plates is dramatically inhibited with the anti-FN-receptor antiserum when compared with NIH3T3. These results indicate that the increased expression of highly branched N-glycans at cell surface is correlated with the rapidness of tumor formation and altered adhesive properties of tumor cells in vivo.

3T3 Cells↗
PubMed1997

Electron microscopic immunohistochemistry of ocular and extraocular pseudoexfoliative material.

To investigate the nature of extraocular pseudoexfoliative (PSX) material, and to validate the hypothesis that the PSX syndrome is a systemic disorder, we studied the immunoreactivity of intraocular and extraocular PSX material from patients with the PSX syndrome using antibodies against proteins of extracellular matrices. Surgical specimens of four different tissues were obtained from human eyes with the PSX syndrome: nine trabecular tissues, three cataractous lenses, six bulbar conjunctivas, and seven lid skins. These tissues were processed for electron microscopic immunohistochemistry, and stained with antibodies against vitronectin, fibronectin, laminin, and elastin, by an indirect immunogold procedure. Density of the gold particles located on the PSX material was estimated by video image analysis. Statistical analysis of the data revealed that the PSX material from trabecular tissues, lenses, bulbar conjunctivas, and lid skins had almost identical immunoreactivity to the antibodies studied. PSX materials of trabecular tissues, lenses, bulbar conjunctivas, and lid skins were found to have not only a similar ultrastructure, but also almost identical immunohistochemical characteristics. These results support the hypothesis that the PSX syndrome is a systemic disorder.

Aged↗
PubMed1997

Inhibitory effect of the intravenous anesthetic, ketamine, on rat mesangial cell proliferation.

We studied the effects of ketamine and propofol on rat cultured mesangial cell (MC) proliferation. The 72-h exposure to ketamine (1-100 microM) inhibited [3H]thymidine incorporation into the MC in a concentration-dependent manner. Propofol, however, was not effective at inhibition of MC proliferation at doses from 1 to 100 microM. Ketamine also decreased the cell number at clinically relevant concentrations and increased adenosine 3',5'-cyclic monophosphate (cAMP) levels in MC. We also studied the effects of ketamine on cytokine-induced [3H]thymidine incorporation into the cells. Ketamine decreased the tumor necrosis factor-alpha (TNF-alpha)-, interleukin 1 (IL-1)-, and interleukin 6 (IL-6)-induced [3H]thymidine incorporation into the cells. It also decreased angiotensin II (Ag II)-induced [3H]thymidine incorporation. These results suggest that ketamine has inhibitory effects on MC proliferation, but that propofol does not. Because ketamine inhibits TNF-alpha-, IL-1-, and IL-6-induced MC proliferation, it may be useful in suppressing the cell growth clinically.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1997

Morphometric examination of the free scapular flap.

In this study we investigated the clinicoanatomic basis of the scapular flap by morphometric examinations of 42 cadavers. Our findings were as follows: With common-trunk type scapular vessels, the maximal lengths of arteries and veins that could be used for a flap pedicle were 93 and 91 mm. With direct-type scapular vessels, the maximal lengths were 95 and 71 mm. In common-trunk type vessels, the mean internal diameter 2 mm distal from the confluence of the scapular vessel was 2.8 mm for arteries and 3.3 mm for veins. In the direct-type vessels, the mean internal diameter 2 mm distal from the confluence of the circumflex scapular vessel was 1.8 mm for arteries and 3.3 mm for veins. The maximal superoinferior dimension of the scapular graft was 28 mm. The maximal lateral dimension of the scapular graft was 12 mm.

Adult↗
PubMed1997

CHARGE association with congenital glaucoma due to maldevelopment of the anterior chamber angle.

PURPOSE: We examined the clinicopathologic features of a male infant with the CHARGE association and bilateral congenital glaucoma. METHODS: Trabeculectomy specimens were obtained from the anterior chamber angle and examined by light and electron microscopy. RESULTS: Histopathologic examination of the trabeculectomy specimens showed immature development of the trabecular meshwork that was covered by the ciliary muscles. There were few intertrabecular spaces because the meshwork was almost completely filled with cells and extracellular substances. Deposition of a granular and/or homogeneous substance was observed in the subendothelial area of Schlemm's canal. CONCLUSIONS: Our patient exhibited features typical of the CHARGE association, but also had congenital glaucoma. We hypothesize that these clinical findings are all mediated by a neurocristopathic mechanism. Our findings suggest that the CHARGE association may predispose to anterior chamber angle maldevelopment, which can lead to congenital glaucoma.

Abnormalities, Multiple↗
PubMed1997

[A case of myeloperoxidase-antineutrophil cytoplasmic antibody (ANCA)-positive crescentic glomerulonephritis induced by propylthiouracil (PTU)].

We have experienced a case of myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA)-related glomerulonephritis induced by propylthiouracil (PTU). A 45-year-old female had been treated with PTU for 4 years after the diagnosis of hyperthyroidism. She was referred to out hospital because of abrupt macroscopic hematuria and moderate proteinuria after several days of upper respiratory tract infection. On admission, her laboratory findings showed deterioration of renal function. Renal biopsy revealed crescentic glomerulonephritis without deposition of immune complexes. Her serology was found to be MPO-ANCA-positive and cytoplasmic-ANCA-negative. Based of these findings, we diagnosed idiopathic crescentic glomerulonephritis. Following the initiation of steroid pulse therapy, her urinary protein excretion and renal function gradually improved in parallel with a decrease in the MPO-ANCA titer. Although steroid therapy effectively responded to their renal function without the withdrawal of PTU, it seems that PTU may be closely associated with the development of (MPO-ANCA)-related glomerulonephritis in this case. Therefore, hyperthyroidism patients treated with PTU should be paced under vigilant observation by monitoring their urinalysis and serum creatinine level.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1996

The consensus motif for phosphorylation by cyclin D1-Cdk4 is different from that for phosphorylation by cyclin A/E-Cdk2.

Cyclin D-Cdk4/6 and cyclin A/E-Cdk2 are suggested to be involved in phosphorylation of the retinoblastoma protein (pRB) during the G1/S transition of the cell cycle. However, it is unclear why several Cdks are needed and how they are different from one another. We found that the consensus amino acid sequence for phosphorylation by cyclin D1-Cdk4 is different from S/T-P-X-K/R, which is the consensus sequence for phosphorylation by cyclin A/E-Cdk2 using various synthetic peptides as substrates. Cyclin D1-Cdk4 efficiently phosphorylated the G1 peptide, RPPTLS780PIPHIPR that contained a part of the sequence of pRB, while cyclins E-Cdk2 and A-Cdk2 did not. To determine the phosphorylation state of pRB in vitro and in vivo, we raised the specific antibody against phospho-Ser780 in pRB. We confirmed that cyclin D1-Cdk4, but not cyclin E-Cdk2, phosphorylated Ser780 in recombinant pRB. The Ser780 in pRB was phosphorylated in the G1 phase in a cell cycle-dependent manner. Furthermore, we found that pRB phosphorylated at Ser780 cannot bind to E2F-1 in vivo. Our data show that cyclin D1-Cdk4 and cyclin A/E Cdk2 phosphorylate different sites of pRB in vivo.

Amino Acid Sequence↗
PubMed1996

The 273rd codon mutants of p53 show growth modulation activities not correlated with p53-specific transactivation activity.

Cancer-related mutations of the p53 tumor suppressor gene are clustered in the four so-called 'hot spots', codons 175, 248, 273 and 281/282. By using recombination PCR in vitro mutagenesis, we introduced point mutations into the codon 273 of wild-type (wt) p53 (pC53-SN3) from Arg to His (pC53-273H [273H]), Asp (273D), Pro (273P), Lys (273K), Leu (273L) or Thr (273T), and compared their biological and biochemical activities with wt p53 and cancer-derived 175H, 248W and 273H/309S. Among them, 273H/309S, 273H and 273D as well as wt p53 transactivated the chloramphenicol acetyltransferase (CAT) gene placed downstream of the p53 binding consensus, while none of the other mutants including 273L did. Transcriptions from human c-fos and rat PCNA promoters were suppressed by wt p53 and 273D, while they were enhanced variously by all other mutants in Saos-2 and/or NIH3T3 cells. On the other hand, growth of human squamous carcinoma cell lines measured by the plating efficiency of G418-resistant colonies was enhanced by transfection of 175H, 248W, 273H/309S and 273P, while suppressed by not only wt p53, 273D and 273H but also 273L. Thus, 273H/309S enhanced cell growth in spite of its p53-specific transactivation activity, while 273L suppressed cell growth in spite of its complete loss of the p53-specific transactivation. We concluded that the sequence-specific transactivation of p53 is not always correlated with its growth inhibitory activity.

3T3 Cells↗
PubMed1996

Cyclin-dependent kinase-2 (Cdk2) forms an inactive complex with cyclin D1 since Cdk2 associated with cyclin D1 is not phosphorylated by Cdk7-cyclin-H.

Cyclin-dependent kinases (Cdks) form complexes with cyclins, and as a consequence they generally express kinase activities. One of these Cdks, Cdk2, is known to bind with cyclins A and E, and plays an important role in the progression of the cell cycle via phosphorylation of target proteins such as the product of the retinoblastoma tumor-suppressor gene (pRB). It has been suggested that Cdk2 bound with cyclin D1 and Cdk2-cyclin-D1 complex show neither H1 histone nor pRB kinase activity. However, it is not clear whether Cdk2-cyclin-D1 has unknown targets and why Cdk2 is not activated by binding with cyclin D1. We investigated these questions using Cdk, cyclin and Cdk-cyclin complexes produced in a baculovirus expression system. Cdk2 formed a complex with cyclin D1 in this system. After extensive purification, Cdk2 was still bound to cyclin D1. The Cdk2-cyclin-D1 complex did not phosphorylate any tested substrates, such as H1 histone, pRB, SV40 large T antigen, p53, E2F-1 or a preparation of nuclear proteins from HeLa cells; in contrast, Cdk2-cyclin-E and Cdk2-cyclin-A phosphorylated these proteins. Moreover, the Cdk2-cyclin-D1 complex was not activated by incubation with Cdk4 or cyclin E. Thus, Cdk2 and cyclin D1 formed a stable complex that was not activated. In order to determine why Cdk2-cyclin-D1 lacks kinase activity, we investigated the phosphorylation of Cdk2. Under-shifted Cdk2, the active form of Cdk2, was not detected in the Cdk2-cyclin-D1 complex in the baculovirus system. In human WI-38 cells, cyclin D1 began to form a complex with Cdk2 as well as with Cdk4 from the mid-G1 phase of the cell cycle. The Cdk2 bound to cyclin D1 in human cells was also the inactive form that was slowly migrated. Moreover, we found that Cdk2 bound to cyclin D1 was not phosphorylated by Cdk7-cyclin-H, while Cdk2 bound to cyclin E, as well as free Cdk2, was was phosphorylated by Cdk7-cyclin-H. Additionally, Cdk2 phosphorylated by Cdk7-cyclin-H did not bind to cyclin D1. These results strongly suggest that Cdk2 forms a stable complex with cyclin D1 but is not activated because the Cdk2 molecule in the complex is not phosphorylated by Cdk7-cyclin-H and the phosphorylated Cdk2, an active form, does not bind to cyclin D1.

Animals↗
PubMed1996

Inhibitory effects of propofol on catecholamine secretion and uptake in cultured bovine adrenal medullary cells.

In the central and peripheral noradrenergic neurons, the balance between noradrenaline release and reuptake determines the level of noradrenaline at the synaptic cleft or the nerve ending. In the present study, we examined the effects of propofol, an intravenous general anaesthetic, on catecholamine secretion and noradrenaline uptake in cultured bovine adrenal medullary cells and on the serum noradrenaline and blood pressure in rats. In cultured adrenal medullary cells, propofol (10-50 mumol/l) concentration-dependently inhibited catecholamine secretion stimulated by carbachol. Propofol suppressed carbachol-evoked 22Na+ influx as well as 45Ca2+ influx at concentrations similar to those which suppressed the catecholamine secretion. Propofol (10-50 mumol/l) also inhibited veratridine-evoked 22Na+ influx, 45Ca2+ influx and catecholamine secretion, whereas it had little effect on the 45Ca2+ influx and catecholamine secretion induced by 56 mmol/l K+. Cultured adrenal medullary cells show [3H] noradrenaline uptake which is sensitive to imipramine. Propofol (10-50 mumol/l) significantly inhibited the imipramine-sensitive uptake of [3H] noradrenaline. In rats, intravenous administration of propofol (2.5 mg/kg) lowered serum noradrenaline and arterial blood pressure. From these findings, in spite of inhibiting noradrenaline uptake, propofol at anaesthetic concentrations (10-30 mumol/l) seems to reduce catecholamine secretion by interfering with Na+ influx through voltage-dependent Na+ channels as well as nicotinic acetylcholine receptor-associated ion channels in the adrenal medulla and, probably, in the sympathetic nervous system. This may explain the propofol-induced hypotension during anaesthesia.

Adrenal Medulla↗