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Biomedical subjects

N Ishihara

Publications and source records attributed to N Ishihara.

At least 37 records · Page 2Linked to original sources

[Short interval change of 99mTc-ethyl cysteinate dimer single photon emission computed tomography in Wilson's disease].

We studied short interval change of cranial computed tomography (CT), magnetic resonance imaging (MRI) and 99mTc-ethyl cysteinate dimer single photon emission computed tomography (99mTc-ECD SPECT) in a case of Wilson's disease. Before treatment, CT scan showed low density changes in the bilateral thalamus and basal ganglia, and MRI demonstrated high intensity in same lesions. 99mTc-ECD SPECT study revealed a hypoperfusion in bilateral thalamus. After 2 months under D-penicillamine therapy, neurological findings had improvement. Hypoperfusion in the thalamus with 99mTc-ECD SPECT significantly improved, whereas abnormal findings of CT scan and MRI persisted. 99mTc-ECD SPECT study may be useful for the planning of the treatment of Wilson's disease.

Adolescent↗

Identification of the protein import components of the rat mitochondrial inner membrane, rTIM17, rTIM23, and rTIM44.

We cloned rat liver mitochondrial 18.1, 21.9, and 51.0 kDa proteins with a significant structural homology to the components of the translocase of the yeast mitochondrial inner membrane, Tim17, Tim23, and Tim44. The 18.1 and 21.9 kDa proteins were synthesized as mature forms having four potential transmembrane segments and localized to the mitochondrial inner membrane. The 51.0 kDa protein is a precursor having a presequence of approximately 6 kDa which is cleaved during import into the mitochondria. The mature 45 kDa protein is located in the matrix, both in a soluble form and in a membrane-bound, alkali-extractable form. Immunofluorescence microscopy confirmed the location of all three proteins in the mitochondria. Antibodies against the 21.9 kDa protein, but not those against the 18.1 and 51.0 kDa proteins, inhibited the precursor import into the mitoplasts in vitro. Immunoprecipitation indicated that all three proteins interacted with the protein in transit to the matrix. Immunoprecipitation also revealed that the 18.1 kDa protein formed a complex with the 21.9 kDa protein and the 45 kDa protein with mHsp70; the latter complex was dissociated in an ATP- or ADP-dependent manner and the reaction was impeded by AMP-PNP or inorganic phosphate. These assays thus demonstrated the 18.1, 21.9, and 45 kDa proteins to be the translocator components of the rat mitochondrial inner membrane and, therefore, the functional homologues of Tim17, Tim23, and Tim44, respectively.

Amino Acid Sequence↗

Characterization of the initial steps of precursor import into rat liver mitoplasts.

Mitochondria have two independent protein-import machineries, one in the outer membrane (the Tom system) and the other in the inner membrane (the Tim system). Here, we have characterized the initial steps of precursor import into rat liver mitoplasts. The import reaction was separated into two stages, consisting of precursor binding to the mitoplasts at 0-10 degreesC, and a subsequent chase reaction at 30 degreesC. This assay revealed four distinct precursor-import steps: DeltaPsi-dependent initial binding of the precursor, precursor transfer to the Tim23-Tim17 stage, DeltaPsi-dependent translocation of the presequence across the inner membrane, and the complete translocation of the mature portion of the precursor. Antibodies against the intermembrane space domain of Tim23 inhibited neither the precursor binding nor the subsequent translocation of the presequence across the inner membrane. In contrast, the antibodies inhibited the complete translocation of the mature domain of the precursor across the inner membrane. Immunoprecipitation with anti-Tim23 IgGs revealed that the precursor-Tim23 complex increased with time and temperature after the initial targeting of the precursor to the mitoplasts. These results suggest that the precursor is first targeted to the inner membrane component DeltaPsi-dependently, then transferred to the Tim system consisting of Tim23-Tim17, and finally imported into the matrix.

Amino Acid Sequence↗

Atypical form of the fourth criterion for transient entrainment.

The typical fourth criterion for transient entrainment is defined when both a sudden shortening in conduction interval to and a distinct change in electrogram morphology at a bipolar recording site are demonstrated while performing overdrive pacing of a reentrant tachycardia from a single pacing site at two different constant rates. The purpose of this article was to test the hypothesis that if an intracardiac recording site showing both orthodromic and antidromic capture with entrainment pacing is located suitably distant from the circuit, sudden shortening in conduction interval to that site may occur without any significant change in the bipolar electrogram morphology (i.e., atypical form of the fourth criterion). Atrial overdrive pacing of orthodromic tachycardia was performed in 20 patients with either left anterior (12 patients) or left posterior (8 patients) accessory pathways. We investigated the effects of overdrive pacing from the proximal or distal coronary sinus, specifically effects on the electrogram interval and the electrogram morphology at the right atrial appendage. Overdrive pacing of orthodromic tachycardia from the proximal coronary sinus was performed in 10 of the 12 patients with left anterior accessory pathways; those 10 patients demonstrated the first entrainment criterion at the right atrial appendage site. Overdrive pacing of orthodromic tachycardia at still shorter cycle lengths demonstrated a sudden shortening in conduction interval to the right atrial appendage site. Despite shortening in conduction interval the morphology of the right atrial appendage electrogram was completely or almost identical to that during orthodromic tachycardia, indicating an atypical form of the fourth criterion. This criterion was not demonstrated in patients with left posterior accessory pathways. Thus, atypical fourth entrainment criterion was demonstrated during overdrive pacing of orthodromic tachycardia from the proximal coronary sinus only in patients with left anterior accessory pathways. Demonstration of atypical fourth criterion seems largely dependent on the location of the accessory pathway, the pacing, and the recording sites.

Adolescent↗

Biology of human trophoblast.

In order to elucidate the regulation of placental growth, we have characterized the expression of proliferating cell nuclear antigen (PCNA), apoptotic DNA fragmentation and bcl-2 protein in human placenta during pregnancy. PCNA and bcl-2 protein expression were examined by immunohistochemical techniques, while the occurrence of apoptotic DNA fragmentation was assessed by in situ analysis of DNA 3'-end labeling method. Both PCNA expression and apoptotic DNA fragmentation were found in cytotrophoblasts (C-cells), being most abundant in early placenta, less abundant in midterm placenta and least abundant in term placenta. In contrast, bcl-2 protein expression was found in syncytiotrophoblasts (S-cells), being least abundant in early placenta, less abundant in midterm placenta and most abundant in term placenta. These data indicate that early placenta is characterized by the highly proliferative activity of C-cells associated with the increased occurrence of apoptosis, whereas term placenta is characterized by the abundant expression of bcl-2 protein in S-cells. Furthermore, effects of EGF on the proliferative activity and differentiated function of trophoblasts were investigated using an organ culture system. Explants of trophoblastic tissues were cultured with or without EGF, in the presence or absence of 10(-8)M triiodo-L-thyronine (T3) in a serum-free condition. In 4-5 week placentas, EGF and EGF receptor were almost exclusively localized in C-cells, and EGF augmented the proliferative activity of C-cells without affecting the ability to secrete hCG and hPL. By contrast, in 6-12 week placentas, EGF and EGF receptor were predominantly localized in S-cells, and EGF stimulated hCG and hPL secretion without affecting the proliferative activity of C-cess. The addition of T3 (10(-8)M) resulted in an increased secretion of immunoreactive EGF by cultured placental explants. These findings suggest that EGF acts as a local factor in regulating early placental growth and function in synergy with thyroid hormone. On the other hand, progesterone selectively inhibited pleise hCG (alpha, beta) mRNAs expression and decreased hCG secretion in normal placental tissues, whereas choriocarcinoma did not respond to progesterone. This suggests that inhibitory regulation of hCG synthesis in choriocarcinoma is different from normal placenta. It was also found that in molar trophoblasts and choriocarcinoma cells PCNA expression was high, but both bcl-2 protein and apoptotic signal expression were low. Characterization of choriocarcinoma hCG revealed that there are striking differences in carbohydrate structures between normal hCG and choriocarcinoma hCG. Sialic acid content in choriocarcinoma hCG was extremely lower compared to that in normal hCG. The detection of the alteration in hCG sugar chains is useful for biochemical diagnosis of choriocarcinoma.

Cell Differentiation↗

Prolonged arterial occlusion caused by thrombus development at sites of arterial bifurcation.

Although thrombogenic atheromas frequently develop at sites of arterial branching or bifurcation, the nature of such thrombus formation remains unclear. In this study, small rat mesenteric arteries (about 0.3 mm id) were observed using a video-microscope system. Exposure of the media by inducing compression damage over a short segment caused occlusive thrombus formation and subsequent spontaneous reperfusion repeatedly over about 30 min. Compression damage was induced either at a site just distal to the bifurcation (group 1, n = 7) or 5-10 mm downstream from the bifurcation (group 2, n = 7). The number of thrombotic occlusions was similar in the 2 groups, but the total duration of occlusion was significantly higher in group 1 (540 +/- 47 sec) than in group 2 (295 +/- 24 sec) (p < 0.01). The total duration of occlusion in group 1 was significantly reduced to 273 +/- 16 sec (p < 0.01) by mechanical interruption of flow in the other, intact, arterial branch. In the presence of blood flow through the intact branch, the occlusive thrombus at the bifurcation further enlarged in the direction of the intact branch, resulting in a significantly larger thrombus than in the absence of blood flow (17.1 +/- 2.1 vs 9.2 +/- 0.9 x 10(-2) mm2, p < 0.01). Stasis of the arterial blood per se did not affect the duration of thrombotic occlusion or increase plasma fibrinolytic activity. Thus, arterial occlusion caused by a thrombus arising at arterial bifurcations may be prolonged because of enlargement of the thrombus owing to the action of platelets in blood flowing through the intact branch.

Aminocaproic Acid↗

Transcatheter neodymium-yttrium-aluminum-garnet laser coagulation of canine ventricle using a balloon-tipped cardioscope.

The feasibility of transcatheter laser ablation of the canine left ventricle (LV) was tested using a newly developed cardioscope. In 17 anesthetized dogs, a combined laser-endoscope catheter, consisting of an endoscope encased in a 7-French flexible catheter with an inflatable and transparent balloon at the distal end, was introduced into the LV via the carotid artery. A 1064-nm neodymium-yttrium-aluminum-garnet (Nd:YAG) laser was delivered by laser optic fiber, which was introduced through the transport channel and positioned inside the saline-filled balloon. In 16 of 17 dogs, the endocardial surface of the LV was clearly observed. Laser energy totaling 500-5,000 J was applied sequentially in 13 dogs and laser irradiation was completed in all but 2 of the dogs. The excised hearts revealed well-demarcated oval-shaped lesions 2.5-9.5 mm deep in 7 of 11 dogs. Histologic sections revealed coagulation necrosis surrounded by a rim of contraction band necrosis. Thus, transballoon laser photocoagulation of the beating LV is feasible. The newly combined laser-endoscope catheter, which is still in its preliminary stages and needs to be improved to increase the success rate of photocoagulation, appears to be a promising alternative modality for catheter ablative therapy for ventricular tachycardia.

Animals↗

[Antioxidants and angiogenetic factor associated with age-related macular degeneration (exudative type)].

To confirm the hypothesis that antioxidants and angiogenetic factors may be associated with the development of age-related macular degeneration (exudative type), we compared serum levels of vitamins A, C, and E and carotinoid, zinc, selenium and b-FGF (basic-fibroblast growth factor) in 35 patients with age-related macular degeneration (exudative type) with the levels in 66 controls. The average serum zinc level was significantly lower in the patient group than in the control group. Serum vitamin E-alpha levels also tended to be lower. Most serum b-FGF levels were below the standard value in each group. Based on the above results, we conclude that subnormal levels of zinc and vitamin E may be associated with the development of age-related macular degeneration.

Aged↗

[A case of Guillain-Barré syndrome treated with plasma exchange and intravenous high-dose immune globulin].

We describe a 69-year-old female with Guillain-Barré syndrome (GBS) whose paresthesia and weakness improved after plasma exchange (PE) and intravenous high-dose immune globulin (i.v.I.G.). She felt a paresthesia in her right arm, and 7 days later she noticed right arm weakness followed by gait disturbance within 2 days. She received a series of 6 PEs, but paresthesia and weakness did not improve. Following the last PE trial of this series, she was treated by i.v.I.G. (0.4 g/kg) for 5 days. After i.v.I.G., paresthesia and weakness improved in a few days. After 2nd series of 6 PEs, she was able to walk. In this clinical course, the treatment of i.v.I.G. after PE seemed to be effective. This case raises the possibility that i.v.I.G. might be the treatment in GBS patients with insufficient effect of PE.

Aged↗

Earlier activation of the distal than the proximal site of the coronary sinus may represent retrograde conduction through AV node: significance of recording of far distal coronary sinus.

During retrograde conduction through an accessory pathway (AP) or the atrioventricular (AV) node, earlier activation of the distal recording site than a more proximal site of the coronary sinus (CS) generally indicates retrograde conduction via a distally located AP. Thus, after successful ablation of a left-sided AP, if the distal CS recording site is activated earlier than a more proximal site retrogradely, it is considered to suggest-in the absence of His-bundle recording or more frequently in the setting of poor recording of the low septal right atrial electrogram-a conduction via a second AP (located more distally), and not conduction via the AV node. Yet, we hypothesized that retrograde conduction through the AV node may activate the far distal site of the CS (CSD) earlier than a more proximal site, as the anterior atrial wavefront, coming retrogradely from the AV node and traveling along the anterior mitral annulus, could reach the CSD earlier than a more proximal site. To test this we studied 18 patients with intact retrograde conduction via the AV node, but without evidence of an AP. The CSD was recorded by means of a quadripolar catheter (interelectrode distance of 2-5 mm); retrograde activation sequence at the distal (CSD1-2) versus proximal (CSD3-4) bipolar recording site was determined during ventricular stimulation. In 12 of 18 patients the CSD1-2 recording site was activated 5-10 ms earlier than the CSD3-4 recording site, in 3 of 18 patients the CSD1-2 site was activated 5 ms later than the CSD3-4 site; in the remaining 3 patients both recording sites were depolarized simultaneously. The results indicate that the CSD was often depolarized earlier than a more proximal site by impulses that conducted to the atria retrogradely via the AV node while the quadripolar recording catheter was placed at the CSD. This observation, although not well documented previously, suggests that the sequence of retrograde atrial activation in the CS should be studied carefully in consideration of the actual location of the mapping catheter in order to correctly diagnose the presence or absence of conduction via an AP.

Adolescent↗

A new cytotoxic compound from a water extract of corn.

A new cytotoxic compound 2 was isolated from a water extract of corn germ. Structural elucidation by spectroscopic data and chemical evidence fully substantiated 2 to be 11 (E)-10-oxo-11-octadecen-13-olide. Compound 2 exhibited considerably strong cytotoxic activity against various cell lines with IC50 of 0.9-2.8 micrograms/ml.

Antineoplastic Agents, Phytogenic↗

Malfolded cytochrome P-450(M1) localized in unusual membrane structures of the endoplasmic reticulum in cultured animal cells.

A conserved region containing three to five proline residues is present just behind the signal-anchor sequence in the amino terminal portion of most microsomal cytochrome P-450s. We have shown that the proline residues are crucial for correct folding in Schizosaccharomyces pombe cells by using mutants of P-450(M1) in which one to three of the proline residues were changed to alanine. To examine the effects of the mutations on the intracellular localization of P-450s, they were expressed in COS-7 cells. They were found to be localized only in the perinuclear loci as patched structures like the Golgi apparatus, while the wild-type P-450(M1) is localized in the reticular structures which are typical for the ER membrane. However, treatment of the cells with Brefeldin A had no effect on the patched structures. Upon co-expression with another ER membrane protein, CD4D, which possesses a double lysine motif, the expressed CD4D was localized not only in the patched structures as the mutated P-450(M1)s, but also in the reticular structures of ER. When the cells were homogenized and then fractionated, the mutated P-450(M1) was recovered mainly in the low-speed precipitate and in the fractions of much higher density than the normal ER membrane. On electron microscopic observation, unusual membranous bodies were observed near the nucleus only when the mutated P-450(M1) was expressed.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

A convenient conversion chart for obtaining serum LDL-cholesterol values.

I devised a convenient conversion chart to obtain the LDL-cholesterol value from the measured total cholesterol, HDL-cholesterol and triglyceride values without calculations. The principles and the practical use of the chart are described. Its application to the development of slide calculators that allow direct reading of LDL-cholesterol value is also discussed.

Cholesterol, LDL↗

Effect of thyrotropin-releasing hormone (TRH) on cerebral blood flow in spinocerebellar degeneration and cerebrovascular disease.

The effect of TRH on cerebral blood flow in patients with spinocerebellar degeneration and cerebrovascular disease was investigated. Cerebral blood flow was measured by the 133Xenon arterial injection method before, and 30 min after, the intravenous administration of 1000 micrograms of TRH. TRH had no effect on mean arterial blood pressure in either group. In the spinocerebellar degeneration group, cerebral blood flow increased slightly after the injection of TRH, from 52.7 +/- 10.5 to 56.7 +/- 16.0 ml/100 g brain/min. In two patients with spinocerebellar degeneration, whose autonomic function was normal and whose brainstem structure appeared normal in the CT scan, cerebral blood flow increased from 54.8 to 66.4 ml (21.2%), and from 68.6 to 79.9 ml (16.5%), respectively. In the patients with cerebrovascular disease, cerebral blood flow did not change (49.7 +/- 10.8 ml before and 49.4 +/- 12.6 ml after TRH). Cerebral blood flow reportedly increases following an intravenous injection of TRH in animals, supposedly due to the activation of intrinsic cerebral vasodilative fibers situated in the submesencephalic brainstem region. Our results are consistent with this hypothesis and with the clinical finding that TRH especially improves ataxia in spinocerebellar degeneration where there is no pyramidal involvement or disorder of deep sensation.

Autonomic Nervous System↗