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Biomedical subjects

K Enomoto

Publications and source records attributed to K Enomoto.

At least 55 records · Page 3Linked to original sources

A randomized controlled comparative study of oral medroxyprogesterone acetate 1,200 and 600 mg in patients with advanced or recurrent breast cancer.

A randomized controlled comparative study of oral medroxyprogesterone acetate (MPA) 1,200 mg (arm I) and 600 mg (arm II) was conducted in 80 patients with advanced or recurrent breast cancer. There were no significant differences between arm I and arm II in terms of response rate, duration of response and survival, or in terms of incidence and severity of adverse reactions. The lowest serum MPA concentration in responders tended to be higher than that in nonresponders. In the cohort of this study, the lowest concentration in partial response was 17.4 ng/ml, suggesting that this level may be the required minimum serum concentration.

Antineoplastic Agents, Hormonal↗

[A case of Creutzfeldt-Jakob disease exhibiting athetosis in the early stage].

A 68-year-old man was hospitalized on 24 June, 1998 because of visual and gait disturbance. A month before admission, he had been aware of blurred or double vision while watching TV. A few days later, he developed dysphagia and clumsiness in the fingers. His gait became unstable and he exhibited restless finger movements. His shoulders and trunk showed torsion while walking. On admission, he became disoriented and showed rigidity in the legs and athetosis in the bilateral fingers. Routine laboratory findings, thyroid function data, and the serum levels of vitamin B1, B12, Cu, and ceruloplasmin were within the normal ranges. Periodic synchronous discharges (PSD) were observed on electroencephalography. MRI showed T2-high intensity and atrophy of the bilateral caudate nucleus and putamen in addition to the cerebral cortex. 99mTc-ECD-SPECT showed a decrease of local blood flow in the bilateral frontal, right temporal, and bilateral parietal lobes and bilateral thalami. Athetosis became exacerbated and was observed for a month, overlapping with myoclonus. We diagnosed the patient as having CJD because of progressive dementia, myoclonus and PSD. Analysis of the prion protein revealed that codon 129 was Met/Met and codon 219 Glu/Glu by DNA sequences. The patient developed akinetic mutism and rigid contracture, and died of pneumonia on 5 September, 1998. Because athetosis is thought to involve the bilateral caudate nucleus, putamen and thalamus, the findings of diagnostic imaging in this patient might be relative to the clinical symptoms.

Aged↗

[Table-moving contrast-enhanced MR angiography of abdominal aortic aneurysm].

Table-moving contrast-enhanced MR angiography (MRA) was performed in 14 cases of abdominal aortic aneurysm to evaluate its clinical usefulness. In all cases, aneurysms were clearly demonstrated and image quality was clinically acceptable. Findings of reconstructed MRA were highly consistent with those of DSA, and thrombosed areas were confirmed on source images. Main aortic branches including renal arteries, common iliac arteries, and internal and external iliac arteries were readily identified on reconstructed MRA and/or source images. Additional findings such as thoracic aortic aneurysm (n = 1), common iliac aneurysm (n = 6), external iliac aneurysm (n = 1), internal iliac aneurysm (n = 1), femoral arterial obstruction (n = 2), and femoral arterial stenosis (n = 4) were also detected. Although table-moving MRA may have disadvantages like reduced blood signal and limited spatial resolution compared with the conventional contrast-enhanced technique, the images that were obtained provided sufficient contrast and resolution for preoperative evaluation. Because abdominal aortic aneurysm is accompanied by various arterial abnormalities in many of the large arteries, table-moving MRA was considered a suitable technique for comprehensive assessment.

Aged↗

[Visiting nurse for a terminal ALS patient].

The authors' hospital is a 585-bed hospital under the direct management of the National Health Insurance System. The hospital has been providing visiting nurses for the past 8 years, who work from local medical centers and the Visiting Nurses Department. Thirty-seven patients have received such home care, among whom 8 had intractable disease. Patient S was a 46-year-old woman who suffered from amyotrophic lateral sclerosis (ALS). The onset of the disease was in April, 1993, when the patient experienced muscular atrophy in both legs and deteriorating muscular strength. The diagnosis was definitive in 1995. On March 1, 1998, the patient received emergency hospitalization for breathing difficulties and aspiration pneumonia, and on March 5 underwent tracheotomy. A cannula had to be inserted for tubal feeding, and the physician in charge explained to her family that her prognosis was 3 months. Both the patient and her family desired home care, and the patient returned home on April 11. Respecting the wishes of the patient, the visiting nurse provided support so that home treatment could be continued. In the end, the patient lived at home while receiving home treatment for 7 months. Through the support provided by the visiting nurse, efforts were made to keep the patient's condition stable, and she was able to continue home treatment and living at home for a higher quality of life.

Amyotrophic Lateral Sclerosis↗

[Rethinking the visiting nurse system at a major regional hospital].

The authors' hospital is a National Health Insurance System Hospital near four cities. It serves as the central hospital for a region with a population of about 330,000 people. The hospital has 585 beds and sees an average of 1,500 outpatients each day. The average number of hospitalized patients each day is 500. Its visiting nurse department is located in a regional medical center and functions as a "Visiting Nurse Center". The purpose of the present study was to review the visiting nurse system at our hospital that has been operating for the past 8 years. The motivation for this review was our intention to actively increase the number of people advantage of such services, and attempt to provide continuous care for each individual patient. By looking back on the system as it has been practiced, its procedures, and results during the 8 years from 1990 to 1997, we can consider points for improvement from among the problem points discovered. The problems uncovered in our practice of home nursing care are listed below. 1. It is difficult to present a list with an estimated period for the release from the hospital. 2. Instructions for leaving the hospital are not sufficiently detailed. 3. Arranging the schedule and actual visits for diagnosis and treatment is complex. 4. The system for cooperation with the activities that are done in the hospital is insufficient. 5. The system for cooperation with local public health nurses is insufficient. 6. The system for managing equipment is insufficient. 7. The 24-hour support system for terminal patients is inadequate.

Community Health Nursing↗

Soluble fumarate reductase isoenzymes from Saccharomyces cerevisiae are required for anaerobic growth.

In Saccharomyces cerevisiae, the cytosolic and promitochondrial isoenzymes of fumarate reductase are encoded by the FRDS and OSM1 genes, respectively. The product of the OSM1 gene is reported to be required for growth in hypertonic medium. Simultaneous disruption of the FRDS and OSM1 genes resulted in the inability of the yeasts to grow anaerobically on glucose as a carbon source, and disruption of the OSM1 gene caused poor growth under anaerobic conditions. However, the disruption of both the FRDS and/or OSM1 genes had no effect on aerobic growth or growth under hypertonic conditions. These results suggest that the fumarate reductase isoenzymes in Saccharomyces cerevisiae are essential for anaerobic growth but not for growth under hypertonic conditions.

Anaerobiosis↗

Endothelial myosin light chain kinase regulates neutrophil migration across human umbilical vein endothelial cell monolayer.

Although extravasation of neutrophils is a critical step in acute inflammation, the role of the endothelial cytoskeleton in neutrophil transmigration has not been fully investigated. We used an in vitro model of neutrophil transmigration across a monolayer of HUVEC cultured on amniotic membrane. Human neutrophils were allowed to migrate across the HUVEC monolayer in response to a gradient leukotriene B4 and then the number of migrated neutrophils were counted microscopically. We also followed endothelial F-actin and myosin filament formation using rhodamine-phalloidin and anti-myosin Ab staining. Myosin light chain (MLC) phosphorylation in endothelial cells was determined by immunoprecipitation of 32P-labeled HUVEC with anti-myosin polyclonal Ab. Normally, neutrophil migration induced F-actin formation, myosin filament formation, and MLC phosphorylation in HUVEC. When HUVEC was pretreated with the myosin light chain kinase (MLCK) inhibitor, ML-9, neutrophil migration was diminished and F-actin formation, myosin filament formation, and MLC phosphorylation were inhibited. Pretreatments of HUVEC with the intracellular calcium ion chelator, bis-(O-aminophenoxyl)ethane-N, N, N', N'-tetraacetic acid acetoxymethyl ester (BAPTA/AM), and the calmodulin antagonist, trifluoperazine, had similar effects. These results indicate that a calcium/ calmodulin-dependent MLCK in endothelial cells regulates neutrophil transendothelial migration.

Actins↗

Regional differences in alpha1-adrenoceptor subtypes and mechanisms in rabbit arteries.

Contractility mediated through alpha1-adrenoceptor subtypes and the maximum binding site (Bmax value) and the dissociation constant (Kd value) for [125I]HEAT ([125I]iodo-2-(beta-(4-hydroxyphenyl)ethylaminomethyl)tetralone) were determined in the following rabbit arteries: thoracic and abdominal aorta, mesenteric, renal and iliac arteries, and the alpha1-adrenoceptor subtypes mediating contractile mechanisms in vascular smooth muscle were studied. The pD2 values for norepinephrine differed considerably among the arteries in the presence of nicardipine (10(-5) M), while the pA2 values for 5-methylurapidil against norepinephrine were identical at low affinity in all the arteries used. In Ca2+-free physiological saline solution (Ca2+-free PSS), the pA2 values for 5-methylurapidil were also similar except for the renal artery, in which there were no stable contractions. In normal PSS, the concentration-response curves for norepinephrine with chloroethylclonidine-pretreatment were shifted to the right (pD2 values of 5.58, 5.70, 5.74, 5.98 and 6.38 for thoracic and abdominal aorta, mesenteric, renal and iliac arteries, respectively). In the [125I]HEAT binding study using membrane preparations obtained from chloroethylclonidine-treated strips, the Bmax values (33.2-105.2 fmol/mg protein) for [125I]HEAT varied considerably among arteries, while the Kd values (0.20-0.26 nM) were identical. The logarithm of Bmax values is proportional to the pD2 values for norepinephrine (slope=0.69, r=0.961). These observations suggest that the regional differences in potency (pD2 value) of the alpha1-adrenoceptor agonist, norepinephrine, are a result of the differences in population and density of alpha1-adrenoceptor subtypes in rabbit arteries.

Adrenergic alpha-1 Receptor Agonists↗

One of the fumarate reductase isoenzymes from Saccharomyces cerevisiae is encoded by the OSM1 gene.

Soluble fumarate reductase from yeast irreversibly catalyzes the reduction of fumarate to succinate and has noncovalently bound flavin adenine dinucleotide. In yeast, there are two isoenzymes of fumarate reductase, which can be distinguished on the basis of their absorption or nonabsorption to DE-52 columns. Previously, we have purified FRDS1 and isolated its gene (FRDS) from Saccharomyces cerevisiae. In the present study, FRDS2 was purified to homogeneity by four chromatography steps. The N-terminal and C-terminal amino acid sequences of FRDS2 were identical to the deduced amino acid sequence of the OSM1 gene (EMBL Database Accession No. L-26347), whose isolation and biochemical properties have not been studied up until now. From these results, we conclude that FRDS2 is encoded by the OSM1 gene. The deduced amino acid sequence of the OSM1 gene revealed that FRDS2 is synthesized as a precursor protein containing a presequence composed of 32 amino acid residues. The mature enzyme consists of a protein of 469 amino acid residues with a molecular weight of 51,370. The N-terminal extension had the characteristics of a typical signal sequence required for targeting and sorting to a noncytosolic destination. In fact, FRDS2 was found to be located in promitochondria.

Amino Acid Sequence↗

Preoperative evaluation of the chemosensitivity of breast cancer by means of double phase 99mTc-MIBI scintimammography.

The chemosensitivity of breast cancer is important for its management, but it is difficult to evaluate preoperatively. Tc-99m hexakis-2-methoxyisobutylisonitrile (MIBI) scintimammography has been reported to indicate the expression of P-glycoprotein, which is one factor concerned with multidrug resistance. We developed a chemosensitivity assay by using surgical specimens to investigate whether 99mTc-MIBI scintimammography findings before the operation are related to chemosensitivity according to our assay. Fifteen patients with primary breast cancer were enrolled into the study. Early and delayed images were obtained at 10 and 120 minutes after intravenous injection of 99mTc-MIBI, respectively. Regions of interest were placed on the tumors and the contralateral healthy breasts in each patient to estimate 99mTc-MIBI uptake in the tumor, and retention indices were then calculated to assess the washout of 99mTc-MIBI. Chemosensitivity assay was performed by incubating surgical specimens with anticancer agents such as doxorubicin, epirubicin, pinorubicin, mitomycin C, cisplatin and 5-fluorouracil. 99mTc-MIBI washout on scintimammography was successfully related to inhibition ratios on chemosensitivity tests when compared with 99mTc-MIBI uptake by the tumor. In particular, high correlation coefficients were obtained between the retention index of 99mTc-MIBI and the inhibition ratios of doxorubicin (r = 0.75), epirubicin (r = 0.60) and pinorubicin (r = 0.62), but poor correlation was found for mitomycin C (r = 0.44) and cisplatin (r = 0.31). Our results indicate that the retention index of 99mTc-MIBI is closely correlated to chemosensitivity to anthracyclines, suggesting that double-phase scintimammography allows preoperative prediction of chemosensitivity of breast cancer.

Adult↗

Hydrogen peroxide derived from hepatocytes induces sinusoidal endothelial cell apoptosis in perfused hypoxic rat liver.

BACKGROUND & AIMS: Evidence is accumulating that hypoxic liver injury involves not only necrosis but also apoptosis. Reactive oxygen species can cause apoptosis. This study examined the hypothesis that H2O2 induces apoptosis in hypoxic rat liver. METHODS: Blood-perfused rat livers were made hypoxic by reducing the perfusion flow. H2O2 was detected by both 2',7'-dichlorofluorescein fluoroimaging and cerium electron-microscopic methods. To evaluate the apoptosis, the liver was stained with the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL) method. To further investigate the involvement of H2O2 in hypoxia-induced liver cell apoptosis, small pieces of liver in the cultured media were exposed to 0.5 mmol/L of reagent H2O2 and stained with the TUNEL method. RESULTS: In the hypoxic liver, H2O2 was produced predominantly by hepatocytes, and the number of apoptotic nonparenchymal cells was significantly increased, particularly in the midzone. All the apoptotic cells were positively stained with monoclonal antibody against the hepatic sinusoidal endothelial cells (SECs). In incubated liver pieces, reagent H2O2 induced apoptosis selectively in SECs. CONCLUSIONS: Low-flow hypoxia induces H2O2 production in hepatocytes, and this H2O2 induces apoptosis selectively in SECs in the rat liver.

Animals↗

The augmentation of intrinsic laryngeal muscle activity by air-jet stimulation of the nasal cavity in decerebrate cats.

The purpose of this study was to examine the functional roles of nasal afferents in modulating the activity of the intrinsic laryngeal muscles. The electromyographic activities of the intrinsic laryngeal muscles and major respiratory muscles were recorded in cats during nasal air-jet stimulation. The activities of brainstem respiratory neurons were also recorded to determine which neurons transmit nasal afferent signals to the intrinsic laryngeal motoneurons. These axonal projections were identified by antidromic activation evoked by stimulation to the spinal cord at C4 level and the laryngeal nerve. The length of the respiratory cycle was prolonged and the diaphragmatic activity was decreased during air-jet stimulation of the nasal cavity. In contrast, the activities of both the intrinsic laryngeal adductor and abductor muscles were increased. Examination of the laryngeal reflexes revealed increase in the activities of intrinsic laryngeal motoneurons during both respiratory phases. Most of the respiratory neurons recorded decreased their peak firing rate during air-jet stimulation, reflecting decreased diaphragmatic activity; however, the peak firing rate of the bulbospinal expiratory neurons in the portion of the ventral respiratory group caudal to the obex did not decrease during stimulation. These findings demonstrate the nasal air-jet stimulation decreases the activities of major inspiratory muscles in order to avoid inspiration of foreign bodies into the nasal cavity and augments the activities of intrinsic laryngeal muscles, enabling prompt elicitation of the laryngeal airway reflex. Our findings also suggest that the nasal afferents suppress the major inspiratory activities by way of brainstem inspiratory neurons, but that the activities of intrinsic laryngeal muscles are controlled through undetermined pathway(s) other than the pathway through respiratory neurons.

Animals↗

Effects of carbamazepine on nerve activity and transmitter release in neuroblastoma-glioma hybrid cells and the frog neuromuscular junction.

Effects of the antiepileptic drug carbamazepine on nerve action potential and transmitter release in mouse neuroblastoma-glioma hybrid cells (NG108-15) and the frog neuromuscular junction were studied. Carbamazepine within a concentration range of 0.1-0.5 mmol/L reduced the peak height of the action potential of the NG108-15 cells, whereas the membrane potential and membrane resistance were unaffected. Voltage clamp revealed that the decrease in the action was due to the blockage of the Na+, delayed K+ and transient Ca2+ currents. Carbamazepine did not affect Ca(2+)-activated and A type K+ currents and long-lasting Ca2+ current. In the frog neuromuscular junction, carbamazepine decreased the mean quantal content by a parallel shift in the frequency augmentation-potentiation (FAP) relation. It is concluded that carbamazepine blocks the voltage-dependent Na+, delayed K+, and transient Ca2+ currents and quantal transmitter release through a decrease of nerve excitation.

Action Potentials↗

Chronic liver injury promotes hepatocarcinogenesis of the LEC rat.

The Long-Evans rat with a cinnamon-like color (LEC) is a mutant rat that spontaneously suffers from chronic liver injury and subsequent hepatocellular carcinoma (HCC) caused by abnormal copper accumulation in the liver. We attempted to elucidate the role of prolonged liver cell injury on LEC rat hepatocarcinogenesis using a copper-deficient diet (CuDD) to inhibit the occurrence of consequent liver injury. The animals were fed the CuDD from the age of 4 weeks until being killed at the age of 10 months. Diethylnitrosamine (DEN) was administered at the age of 8 weeks. Groups fed a basal diet (BD) with or without the administration of DEN were also assigned as control groups. The animals fed the BD manifested liver injury, while those fed the CuDD did not show liver dysfunction until death. The number and volume of glutathione S-transferase placental form (GST-P)-positive preneoplastic lesions in the liver, which were calculated from the data on two-dimensional planes, were examined to clarify the promotive effect of chronic liver injury on the development of HCC. Regarding the size of the lesions, which indicated the intensity of the promotive effect, the lesions in the livers of rats fed the BD with DEN were much larger than those of rats fed the CuDD with DEN. Feeding the LEC rats with CuDD completely suppressed the manifestation of liver injury, and it was clearly shown that prolonged liver injury had a promotive effect on the LEC rat hepatocarcinogenic process.

Alanine Transaminase↗

Rapid serodiagnosis of Mycobacterium avium-intracellulare complex infection by ELISA with cord factor (trehalose 6, 6'-dimycolate), and serotyping using the glycopeptidolipid antigen.

Mycobacterium avium-intracellulare complex (MAC) is one of the most important opportunistic pathogens, particularly in patients with acquired immunodeficiency syndrome (AIDS). The aim of this study was to determine whether an enzyme-linked immunosorbent assay (ELISA) using trehalose 6,6'-dimycolate (TDM) as an antigen can be used for the rapid serodiagnosis of MAC infection. We also identified MAC serotypes by ELISA using serotype-specific glycopeptidolipid (GPL) antigen. To confirm our findings, the thin-layer chromatographic (TLC) behavior of serotype-specific GPL of the strains isolated from MAC-infected patients was also tested. Forty patients infected with MAC and 30 healthy controls were tested. Thirty-two of the 40 MAC-infected patients had higher titers of serum antibodies against MAC TDM than against MTB TDM, while all 30 healthy control sera were unreactive to MAC TDM and MTB TDM. Results of the GPL ELISA indicated that 20 of the 40 MAC-infected patients' sera were reactive against serotype 4 GPL, 3 against serotype 8 GPL, and 1 against serotype 16 GPL. A TLC analysis of the GPL of the 40 MAC isolates showed that 16 strains were of serotype 4, 5 of serotype 8, and 2 of serotype 16. Results of the GPL ELISA were in good accord with those of the TLC analysis for most patients. Our findings suggest that ELISA using TDM is useful for rapid serodiagnosis of MAC infection, and that complementary ELISA testing using serotype-specific GPL gives additional detailed information concerning MAC serotypes.

Adult↗

Analysis of the sinusoidal endothelial cell organization during the developmental stage of the fetal rat liver using a sinusoidal endothelial cell specific antibody, SE-1.

The sinusoid organization during the development of fetal rat livers was studied using a SE-1 antibody, which we have previously established as a specific monoclonal antibody against rat sinusoidal endothelial cell (SEC). Expression and localization of the SE-1 antigen in the liver tissues of 13- to 21-day-old fetuses were immunofluorescently and immunoelectron microscopically examined. The first positive fluorescence was observed in the immature liver of 15-day-old fetuses. The initial positive staining was randomly distributed in the liver parenchyma and showed no direct relation to the large vessels which may be derived from the fetal vitelline veins. The positive linear staining increased in number and connected with each other during the course of development. The SE-1 staining pattern and the sinusoidal arrangement became similar to those of the adult liver after 20th day of gestation. Immunoelectron microscopically, the immature SEC showed a weak positive reaction for the SE-1 antigen at their membrane and was observed together with immature hepatocytes and hematopoietic cells in the 15-day-old fetal liver. Along with the liver development, SEC formed a sinusoid structure closely associated with hepatocytes and came to strongly express the SE-1 antigen. These results indicate that the organization of the hepatic sinusoid may start at around 15th day of the gestation and occurs randomly in the fetal liver parenchyma. It is also suggested that the expression of SE-1 antigen is possibly regulated by the intimate association with hepatocytes.

Animals↗

Differences of antagonism for a selective alpha1D-adrenoceptor antagonist BMY 7378 in the rabbit thoracic aorta and iliac artery.

Based on the affinity of alpha1D adrenoceptor subtype for a selective antagonist BMY 7378, we studied its functional role in rabbit thoracic aorta and iliac artery, and evaluated the subtypes of the alpha1-adrenoceptors that are activated by phenylephrine (a full agonist) and tizanidine (a partial agonist). In thoracic aorta, the concentration response curves of phenylephrine and tizanidine were antagonized by BMY 7378 with low potency (pA2 values 6.68+/-0.06 and 6.67+/-0.06, slopes of Schild plot 1.06+/-0.04 and 1.01+/-0.04, respectively). On the other hand, in iliac artery concentration response curves for phenylephrine were potently antagonized by a low concentration of BMY 7378, and the slope (0.75+/-0.02) of the Schild plot was significantly different from unity. In iliac artery, a concentration response curve of tizanidine was antagonized by BMY 7378 with low potency (pA2 value 6.64+/-0.08, slope of Schild plot 1.01+/-0.05). These results suggest that an alpha1D-adrenoceptor subtype contributes to alpha1-adrenoceptor mediating muscle contraction in iliac artery, but not in thoracic aorta of rabbit, and that it is activated by a full agonist phenylephrine but not by a partial agonist tizanidine.

Adrenergic alpha-1 Receptor Antagonists↗

Enzyme therapy in Gaucher disease type 2: an autopsy case.

A Japanese patient with Gaucher disease type 2 was treated with enzyme therapy, alglucerase, from 7 to 22 months of age. Whereas hematologic parameters were normalized and hepatosplenomegaly was alleviated, no improvement in neurologic symptoms occurred, and the patient died of respiratory failure at age 22 months. Postmortem examination revealed massive intra-alveolar infiltration of Gaucher cells in lungs and in the central nervous system, i.e., the presence of Gaucher cells in the perivascular Virchow-Robins spaces in the cortex and deep white matter and extensive lamilar necrosis with reactive proliferation of blood vessels and macrophage infiltration of the cerebral cortex. It is suggested that enzyme therapy, with thus far recommended dose, does not prevent long-term respiratory and central nervous system involvement in severe varients of Gaucher disease.

Brain↗