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Biomedical subjects

K Kamiya

Publications and source records attributed to K Kamiya.

At least 127 records · Page 7Linked to original sources

Intracellular pharmacodynamics of ara-C and flowcytometric analysis of cell cycle progression in leukemia chemotherapy.

To establish the most effective and reasonable mode of combining and administrering ara-C with other antileukemic agents in chemotherapy for acute leukemia, the action mechanisms of ara-C was investigated in terms of intracellular pharmacodynamics and the biochemical action mechanism of ara-C was investigated in leukemic cell. Rensonable methods of administering the agent was considered as follows. 1. A low level of ara-C in the incubation medium induced a higher concentration of ara-CTP in leukemic cells. Therefore, maintenance of even a low plasma ara-C level after ara-C therapy could enhance the antileukemic effect of the agent. 2. Ara-C activation was increased in the presence of 6MP by suppressing elevation of deaminase activity in the cell suspection medium. Therefore, administration of 6MP prior to ara-C therapy could enhance the antileukemic effect of the agent. 3. Ten micrograms/ml of ara-C, corresponding to intermediate dose ara-C therapy, induced rapid endonuclease activation, DNA ladder fragmentation and subsequent apoptosis in large numbers of leukemic cells, suggesting that intermediate dose ara-C therapy is effective in reducing residual leukemic cells after therapy. 4. Blood transfusion for patients with high grade anemia prior to bebenoyl ara-C therapy prolonged higher and longer plasma drug maintenance. 5. Flowcytometry of cell cycle progression of L1210 cells treated by ara-C and daunorubicin revealed that a combination of ara-C first and daunorubicin second was superior to the reverse sequential combination. These improvements in the mode of administering ara-C could provide better results following chemotherapy for leukemia.

Animals↗

[Non-Hodgkin's lymphoma associated with polymyositis].

A 67-year-old man was admitted to with severe nasal congestion. One year previously, he had been suffered from polymyositis (PM) and had been treated with prednisolone. Physical examination and computed tomography revealed a mass in the upper pharynx. Biopsy revealed non-Hodgkin's lymphoma (diffuse medium, B-cell type). Bone marrow aspiration also revealed the infiltration by lymphoma cells. The patient achieved a complete remission after combination chemotherapy (cyclophosphamide, adriamycin, vincristine, prednisolone). However, one month later, he suffered from central nervous system involvement of lymphoma cells, and he died of an aspiration pneumonia. Polymyositis/dermatomyositis associated with non-Hodgkin's lymphoma is extremely rare.

Aged↗

Localised thrombus in the distal aortic arch: its aetiology analysed by three-dimensional mould model of the thoracic aorta.

Isolated thrombus of the thoracic aorta without aneurysmal change or dissection is a relatively rare event. A case presenting with aortic thrombus and successive distal embolism is reported herein and the aetiology of the thrombus of the distal aortic arch is analysed by a three dimensional aortic model. A 61-year-old man suffered acute ischaemia in his right leg on January 26, 1994. Enhanced computed tomography (CT) showed a localized thrombus in the distal aortic arch expanding towards the descending aorta, and partial infarction of the left kidney and the spleen. Angiography demonstrated abrupt occlusion of the right superficial femoral artery. Immediate anticoagulation with heparin and coumadin was administered, and the thrombus in the aorta disappeared following 1 month of this medical treatment, leaving the renal and splenic infarction unchanged. The unresolved occlusion of the superficial femoral artery and the popliteal artery was treated with a bypass from the right superficial femoral artery to the peroneal artery using a reversed saphenous vein graft. The mould model of the thoracic aorta was reconstructed from CT, and the thrombus was found to be at the most distal and medial site of the lesser curvature of the aortic arch. This specific location is referred mostly as the site for thrombus formation in the literature. The case is reported briefly and the risk of this specific region of the thoracic aorta for thrombus formation is discussed using this mold model.

Angiography↗

[Modification of the surgical strategy based on intraoperative echographic findings of atherosclerotic ascending aorta].

To prevent the atheroembolic complications such as brain infarction due to the manipulation of atherosclerotic ascending aorta during cardiac surgery, the ascending aorta of 55 patients including 6 emergencies (mean age: 67.7 +/- 6.9 years, valvular disease: n = 12, ischemic heart disease only or combined with valvular disease: n = 43) were evaluated with intraoperative echography as a routine, to enable a proper placement of the cannulae, clamp etc. Irregular elevated lesions into the aortic lumen from the intima were identified in 7 patients (13%, mean age: 71.0 +/- 6.9 years) of ischemic heart disease, which included 2 emergent cases. Arch cannulation was employed in 3 patients with wide-spread lesions on the posterior wall and femoral cannulation was done in 1 patient with wide-spread lesions on the anterior wall. Two of these patients received CABG with in situ arterial conduits under ventricular fibrillation, and the other 2 patients received CABG with aortic cross clamping at the lesion-free site during proximal anastomosis of vein grafts (single clamp technique). Two patients with localized lesion were done CABG with partial aortic clamping and one of them had cerebral infarction during the operation. We recognized that manipulation of the ascending aorta has to be done with a meticulous care and well away from the diseased site. In another patient with localized lesion, the arch cannulation and the single clamp technique were used 2 cm away from that lesion. The brain infarcted patient completely recovered without any sequelae and the others also had no atheroembolic complications. Although calcified lesions on CT were correlated with atheromatous lesions on echogram (p = 0.004), these atheromatous plaques were not detected by enhanced CT, except in only one patient. For screening of the atherosclerosis of ascending aorta, the CT examination was not so effective and the intraoperative echography was the most sensitive and could be easily accomplished. In conclusion, in order to prevent the atheroembolism that might occur due to the improper manipulation of the diseased ascending aorta during usual procedures, surgical strategies have to be modified according to the position, extent and quality of the atherosclerotic lesions, diagnosed by intraoperative echoscanning of the aorta.

Aged↗

Immunocytochemistry of Kv1.5 potassium channel protein in cultured neonatal rat ventricular myocytes.

Of the six voltage-gated potassium channel subunits detected in adult rat heart, Kv1.5 channel is abundant and its expression is depressed in hypertrophied and infarcted myocardium. The effect of nonmyocyte cells (NMCs) on cardiac Kv1.5 channel expression was studied in cultured neonatal rat ventricular cells, using immunofluorescent cytochemistry with a polyclonal antibody against rat Kv1.5 channel protein. Co-culture with NMCs induced myocyte hypertrophy, but a downregulation of Kv1.5 channel expression. Similar changes were observed when pure myocyte culture was treated with medium supernatant of pure NMC culture. These findings suggested that some soluble factors produced by cardiac NMCs play important roles in the regulation of potassium channel density during myocardial hypertrophy.

Animals↗

Inhibition of the 3' --> 5' exonuclease of human DNA polymerase epsilon by fludarabine-terminated DNA.

Incorporation of the anticancer drug fludarabine (9-beta-D-arabinofuranosyl-2-fluoroadenine 5'-monophosphate; F-ara-AMP) into the 3'-end of DNA during replication causes termination of DNA strand elongation and is strongly correlated with loss of clonogenicity. Because the proofreading mechanisms that remove 3'-F-ara-AMP from DNA represent a possible means of resistance to the drug, the present study investigated the excision of incorporated F-ara-AMP from DNA by the 3' --> 5'-exonuclease activity of DNA polymerase epsilon from human leukemia CEM cells. Using the drug-containing and normal deoxynucleotide oligomers (21-base) annealed to M13mp18(+) DNA as the excision substrates, we demonstrated that DNA polymerase epsilon was unable to effectively remove F-ara-AMP from the 3'-end of the oligomer. However, 3'-terminal dAMP and subsequently other deoxynucleotides were readily excised from DNA in a distributive fashion. Kinetic evaluation demonstrated that although DNA polymerase epsilon has a higher affinity for F-ara-AMP-terminated DNA (Km = 7.1 pM) than for dAMP-terminated DNA of otherwise identical sequence (Km = 265 pM), excision of F-ara-AMP proceeded at a substantially slower rate (Vmax = 0.053 pmol/min/mg) than for 3'-terminal dAMP (Vmax = 1.96 pmol/min/mg). When the 3'-5' phosphodiester bond between F-ara-AMP at the 3'-terminus and the adjacent normal deoxynucleotide was cleaved by DNA polymerase epsilon, the reaction products appeared to remain associated with the enzyme but without the formation of a covalent bond. No further excision of the remaining oligomers was observed after the addition of fresh DNA polymerase epsilon to the reaction. Furthermore, the addition of DNA polymerase alpha and deoxynucleoside triphosphates to the excision reaction failed to extend the oligomers. After DNA polymerase epsilon had been incubated with 3'-F-ara-AMP-21-mer for 10 min, the enzyme was no longer able to excise 3'-terminal dAMP from a freshly added normal 21-mer annealed to M13mp18(+) template. We conclude that the 3' --> 5' exonuclease of human DNA polymerase epsilon can remove 3'-terminal F-ara-AMP from DNA with difficulty and that this excision results in a mechanism-mediated formation of "dead end complex."

Base Sequence↗

Ion channel blockers in the treatment of chronic heart failure.

Strategies for pharmacological treatment of chronic congestive heart failure (CHF) are discussed from the viewpoint of cardiac ion channel modulations. It remains controversial as to whether Na channel blockers, which are the most effective drugs to suppress ventricular arrhythmias, can improve the prognosis of chronic CHF. As far as recent knowledge of interactions between the Na channel and its blocker is concerned, lidocaine-like agents such as mexiletine, which inhibit the Na channel current by binding to the channel in the inactivated state, are recommended because they can suppress premature ventricular contractions without prolongation of QRS complexes of sinus beats. To develop a new agent for the treatment of chronic CHF, we extracted the common features of electropharmacologic actions shared by amiodarone and vesnarinone, both of which have been reported to reduce the mortality of patients with chronic CHF. It is concluded that increases in the action potential duration (APD) of ventricular muscle mediated through an inhibition of the delayed rectifier K channel (IK channel) and a reduction of sinus node firing through an inhibition of L type Ca channel in addition to IK channel inhibition, are essential for the treatment of chronic CHF.

Amiodarone↗

Expression of estrogen receptor and proto-oncogene messenger ribonucleic acids in reproductive tracts of neonatally diethylstilbestrol-exposed female mice with or without post-puberal estrogen administration.

Perinatal treatment of female mice with natural and synthetic estrogens including diethylstilbestrol (DES) results in estrogen-independent persistent proliferation and cornification of the vaginal epithelium. The dynamics of the induction of estrogen receptor (ER), c-jun, c-fos and c-myc mRNAs by 17 beta-estradiol (E2) was examined in the uterus and vagina of neonatally DES-exposed and -unexposed ovariectomized adult mice. In the uterus of neonatally DES-unexposed ovariectomized mice, the expression of ER mRNA increased within 1 h after E2 administration and declined by 12 h thereafter. ER mRNA in the vagina decreased within 1 h after the stimulation and recovered by 12 h thereafter. In the uterus, c-jun and c-fos mRNAs increased in concentration within 1 h after E2 administration, showing a peak 3 h after the stimulation; they decreased with time thereafter. In the vagina, the concentration of c-jun and c-fos mRNAs increased rapidly, reaching a peak within 1 h after the stimulation. However, the expression of c-myc in uterus and vagina was not changed by postpuberal E2. These results suggest that estrogen regulation of ER and proto-oncogene mRNAs in the vagina differs from those in the uterus. In the neonatally DES-exposed ovariectomized adult mice, uterine ER mRNA expression levels were significantly higher than in the unexposed ovariectomized controls; however, vaginal levels were drastically lower than in the controls. Expression of c-jun and c-fos mRNAs was greater in both the uterus (3- and 6-fold, respectively) and the vagina (18- and 4-fold) of neonatally DES-exposed mice than in controls. The ER mRNA and the increased levels of c-fos and c-jun mRNAs in both uterus and vagina of neonatally DES-exposed ovariectomized mice were not further altered by post-puberal E2 and may be related to ovary-independent persistent changes in the genital tract.

Animals↗

Definitions of severely mentally and physically disabled children in Japan: do the differences affect the prevalence rates of these children?

The prevalence rate of severely mentally and physically disabled children (SDC) aged 6-15 years in Okinawa prefecture on 1 May 1989 was 0.74/1000 (143/192,038) according to Oshima's classification, compared with 0.89/1000 (170/192,038) according to the Ministry of Education's classification with minor modifications. The number of children in region classes 1, 2, 3 and 4 of Oshima's classification for SDC were 100, 34, 6 and 3, respectively. The difference (n = 27) between the total numbers of SDC according to the two classifications was mainly because of 21 children categorized as "walking with support' who were included as SDC according to the Ministry of Education's classification but not as SDC according to Oshima's classification. Only region class 1 of Oshima's classification corresponded with region class 25 of the Ministry of Education's classification. The results of the present study indicate that the differences between the two definitions of SDC affect the reported prevalence rates of SDC. Therefore, changing patterns in the prevalence of SDC should be assessed by serial surveys using the same method in each district.

Adolescent↗

Changes in action potentials and ion currents in long-term cultured neonatal rat ventricular cells.

A primary culture of neonatal ventricular myocytes isolated from day-old rats was established for investigating the changes in action potentials and ion currents over long periods. Cells at days 5 and 15 in culture were studied. These changes in vitro were compared with those in situ derived from the age-matched freshly isolated cells. During primary culture, quiescent cells demonstrated shortening of action potential durations (APD) resembling the developmental changes observed in situ. The beating cultured cells were not associated with APD shortening. Despite constant current amplitudes, the densities of Ca2+ currents (ICa) decreased in the quiescent cultures at later ages as a result of cell enlargement. ICa densities were maintained in the beating cultured and freshly isolated cells. Acceleration in the inactivation of ICa was observed during developments both in vitro and in situ. In addition, the densities of transient outward currents (Ito) tripled and doubled in the quiescent and beating cells during 15-day cultures. However, Ito in beating cultured cells made less contribution to APD in contrast to the quiescent cultured and freshly isolated myocytes. These findings demonstrate that electrophysiological properties differ between two types of long-term cultured cells. ICa densities remained constant in the beating cultures, suggesting that cell beating may be required for the maintenance of ICa density in developing cardiomyocytes.

Action Potentials↗

Thoracoabdominal aortic aneurysm in an infant treated by thromboexclusion with thoracoabdominal aortic bypass. A case report.

A case of a huge thoracoabdominal aortic aneurysm in an eighteen-month-old boy is reported. Surgical treatment was successfully performed by thromboexclusion of the aneurysm with thoracoabdominal aortic bypass using a low-porosity woven Dacron graft 10 mm in diameter and of sufficient surplus length. During the early postoperative period, he developed moderate hydronephrosis, owing to compression of the left ureter by the graft, but no further deterioration was seen. Follow-up angiographies performed four and six years after surgery revealed straightening of the graft and slight stretching of the aorta at the distal anastomosis, but no stenosis was found. Now, seven and a half years after surgery, he has no pressure gradient between upper and lower extremities.

Angiography, Digital Subtraction↗

Cine magnetic resonance imaging study of blood flow and wall motion of the aortic arch.

The aortic arch has 3D distortions in the transverse arch in the axial view, and we previously reported that this distortion is a risk factor in the pathogenesis of arch aneurysms. In this study, we evaluated blood flow and movement of the aortic arch. In 10 healthy young volunteers, ECG-gated cine magnetic resonance imaging was carried out in the axial plane of the transverse arch, the coronal plane of the ascending arch, and the long axial plane along the entire arch. 1. Left anterolateral movements around the midpoint of the transverse arch in the systolic phase were observed in all of the men (6.3 +/- 1.59 mm) and women (4.8 +/- 0.73 mm). 2. A jet flow was detected in the systolic phase along the right side of the aortic wall. At the top of the plane, this jet flow turned to the left in a clockwise rotation in the anterior view. 3. In the long axial plane, a turbulent flow in the systolic phase was observed distal to the left subclavian arterial orifice in 6 of the 7 cases. In conclusion, this turbulent flow and left anterolateral wall motion of the transverse arch are due to anatomical three-dimensional distortion of the transverse arch. We propose that these phenomena may be important risk factors in the pathogenesis of arch aneurysms.

Aorta, Thoracic↗

Effects of long-term oral administration of amiodarone on the ventricular repolarization of rabbit hearts.

The chronic effects of amiodarone on ventricular repolarization were investigated in Langendorff-perfused rabbit hearts in comparison with the acute effects of other Class III antiarrhythmic drugs. Forty to fifty electrograms were recorded through modified bipolar electrodes from the anterior to the lateral epicardial surface of the ventricles under His-bundle pacing (1.0 Hz). In control hearts, epicardial activation proceeded from the apex to the base. The interval from the initial sharp negative deflection of the QRS complex to the apex of the T-wave (Q-aT), which reflects the action potential duration (APD) at the recording site, was longest in the apex and shortest in the base. Therefore, repolarization proceeded from the base to the apex. In hearts treated with oral amiodarone (100 mg/kg, 4 weeks), Q-aT was uniformly prolonged by 14-16% throughout the entire mapped area, whereas the activation sequence was unaffected, and a normal Q-aT gradient was well preserved from the apex to the base. The spatial inhomogeneity of left ventricular repolarization was not enhanced by drug treatment. Acute application of sotalol (30 mumol/L), E-4031 (0.1 mumol/L) or MS-551 (1.0 mumol/L) caused a much greater Q-aT prolongation in the apex than in the base, resulting in a marked enhancement of the spatial inhomogeneity of repolarization. These findings suggest that the propensity of chronic amiodarone to induce torsade de pointes less often than other Class III agents may result at least in part from its favorable effect on the spatial homogeneity of ventricular repolarization.

Administration, Oral↗

Induction of a germline mutation at a hypervariable mouse minisatellite locus by 252Cf radiation.

Male C3H/HeN mice were exposed to 252Cf radiation and mated with unirradiated C57BL/6N females. F1 mice were analyzed for germline mutation at the paternally derived C3H/HeN allele of a hypervariable minisatellite locus, Ms6hm. This locus exhibited a high frequency of length change mutation spontaneously, and the mutation frequency of the paternally derived C3H/He allele in F1 mice born to unirradiated males was 8.4%. Exposure of male mice to 252Cf radiation resulted in even higher frequency of germline mutation. The spermatid stage germ cells were most sensitive to neutrons, and the mutation frequencies of the paternal allele were elevated to 18%, 26% and 24% for 0.35, 0.7 and 1.02 Gy of 252Cf radiation, respectively. Spermatozoa and spermatogonia stages were less sensitive and the mutation frequencies for 1.02 Gy of 252Cf radiation were 16% and 19%, respectively. The 252Cf radiation consisted of 35% gamma-rays and 65% neutrons. Assuming that these two radiations act additively, RBE of 252Cf neutrons for the induction of minisatellite mutation was calculated to be 5.9 for spermatozoa stage irradiation, 2.6 for spermatid stage irradiation and 6.5 for spermatogonia irradiation.

Alleles↗

Acute and chronic effects of amiodarone on mammalian ventricular cells.

This article reviews experimental studies on the electrophysiological effects of amiodarone on mammalian hearts. Acute application of amiodarone (0.1-10 microM) to papillary muscles or single ventricular cells isolated from rabbits or guinea pigs caused a significant decrease in action potential duration (APD) as well as a marked use-dependent inhibition of the maximum upstroke velocity (Vmax) of action potential with fast recovery kinetics. Acute amiodarone also caused a concentration-dependent decrease in the calcium current (ICa) and the delayed-rectifier potassium current (IK). Action potentials recorded from papillary muscles or single ventricular cells isolated from the rabbits treated with oral amiodarone (100 mg/kg daily, 4 weeks) were characterized by a moderate frequency-independent prolongation of APD. There was no use-dependent Vmax inhibition. The ventricular cells treated with chronic amiodarone showed a significant decrease in the current density of ICa, IK and Ito. The amount of mRNA for Kv1.5, a Shaker-related potassium channel from the rats treated with chronic oral amiodarone was significantly lower than that from control rats. These results suggest that the major and consistent effects of chronic amiodarone is repolarization delay (Class III action) through a decrease in IK and Ito density, probably due to a modulation of gene expression of potassium channels. When amiodarone above a certain concentration is present in the extracellular space, fast kinetic Class I and Class IV actions would be added as acute effects.

Action Potentials↗

Cloning of mRNA sequences for two antibacterial peptides in a hemipteran insect, Riptortus clavatus.

Escherichia coli injection rapidly induced bactericidal activity in the hemolymph of a hemipteran insect, Riptortus clavatus. This activity reached its maximum at 9 hr after injection and thereafter declined slowly. Two types of cDNA clones involved in this response were isolated by differential screening. The predominant type encoded for an open reading frame of 678 amino acids, which consisted of fourteen tandem repeats. Each repeat was rich in charged residues and had a proline-rich region which had striking sequence similarities to proline-rich antibacterial peptides from other insect species, indicating these clones encode a multipeptide precursor of antibacterial peptides. The other type encoded for a glycine-rich peptide similar to a known antibacterial peptide as well. Northern blot analyses revealed rapid induction of mRNAs corresponding to these clones after the injection. To our knowledge, this is the first report on the mRNA sequences of antibacterial peptides of hemimetabolous insects, and the second report on the occurrence of multipeptide precursor structure in insect antibacterial peptides.

Animals↗

Intraluminal tumor of the common bile duct as a metastasis of renal cell carcinoma.

A 57-year-old woman was admitted for evaluation of liver dysfunction. A physical examination revealed jaundice and a left abdominal mass, which was diagnosed as being a large renal tumor. Cholangiography showed a smooth filling defect 1 cm in diameter at the common bile duct. Left nephrectomy, and resection of the common bile duct were performed. The pathological diagnosis was metastasis of the common bile duct wall resulting from renal cell carcinoma. Metastatic common bile duct tumors are extremely rare. However, it is important to consider that this is one of the causes of obstructive jaundice.

Carcinoma, Renal Cell↗

Turbo spin-echo magnetic resonance imaging depiction of facial nerve compression by a vertebral artery in a patient with hemifacial spasm--technical note.

Turbo spin-echo magnetic resonance (MR) imaging of a patient with hemifacial spasm clearly demonstrated vascular compression of the facial nerve by the vertebral artery. The high resolution images of this method may be an appropriate alternative to preoperative cerebral angiography. Turbo spin-echo MR imaging is a diagnostic procedure of choice for patients with hemifacial spasm and possibly trigeminal neuralgia.

Adult↗