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Biomedical subjects

K Goto

Publications and source records attributed to K Goto.

At least 559 records · Page 31Linked to original sources

Gene cloning, sequence, expression and in situ localization of 80 kDa diacylglycerol kinase specific to oligodendrocyte of rat brain.

A 3.1 kbp cDNA clone encoding diacylglycerol (DG) kinase of 80 kDa (80K-DG kinase) was isolated from a rat brain cDNA library. The deduced amino acid sequence was 82% homologous to previously identified porcine 80K-DG kinase and contained zinc finger-like sequences, E-F hand motifs and ATP-binding sites similar to the porcine counterpart. By in situ hybridization histochemistry of rat brain at postnatal week 3, the expression signals for 80K-DG kinase mRNA appeared predominantly on somata of discrete cells in the white matter, and the expression pattern was similar to that of the myelin-specific proteins. In immunohistochemistry using the antibody against bacterially expressed DG kinase-fusion protein, numerous fibrous or dot-like structures exhibiting the immunoreactivity were concentrated in the white matter and they were arranged to radiate in the cerebral cortex and the cerebellar granular layer in a pattern almost identical to that of oligodendrocytes. No neuronal cells exhibited the immunoreactivity. The present finding thus strongly suggests that 80K-DG kinase is expressed specifically in the oligodendrocytes, but not neurons, and may be involved in the myelin formation and metabolism. In addition, the intense hybridization signals and the immunoreactivity for this protein were detected in the entire medulla of the thymus and the periarterial lymphatic area of the splenic white pulp both of which represent T-cell-dependent areas.

Amino Acid Sequence↗

Enhancement of host defense by Y-25510, (+-)-3-[4-(2-dimethylamino-1-methylethoxy)phenyl]-1H-pyrazolo[3,4 -b] pyridine-1-acetic acid, a novel synthetic compound. A comparison with recombinant human granulocyte colony-stimulating factor in 5-fluorouracil-treated mice.

The effect of a novel synthetic compound, Y-25510, (+-)-3-[4-(2-dimethylamino-1-methylethoxy)phenyl]-1H-pyrazolo[3,4 -b] pyridine-1-acetic acid, on recovery from long-lasting leukopenia induced by 5-fluorouracil was compared with that of recombinant human granulocyte colony-stimulating factor (rhG-CSF). When mice were administered i.p. with 5-FU (200 mg/kg) on days 0 and 7, intravenous administration of Y-25510 (100 and 1000 micrograms/kg) prevented the decrease in the peripheral leukocyte and neutrophil number and accelerated the recovery from leukopenia. Subcutaneous administration of rhG-CSF (50 micrograms/kg) did not prevent leukopenia but accelerated the recovery from leukopenia. In particular, peripheral neutrophil number increased over a normal level. The administration of Y-25510 (10, 100 and 1000 micrograms/kg) restored the decrease in the number of bone marrow cells, spleen cells, lymphocytes, neutrophils and monocytes. The administration of rhG-CSF (50 micrograms/kg) restored the decrease in the number of bone marrow cells, spleen cells, and neutrophils but not that of lymphocytes and monocytes. In fractions of bone marrow cells on day 21, the administration of Y-25510 (1000 micrograms/kg) showed a tendency of restoring the decrease in neutrophil number. In conclusion, the administration of Y-25510 prevented leukopenia and accelerated the recovery from leukopenia in the 5-FU-treated mice. It is suggested that the mechanism of the restorative action of Y-25510 is different from that of rhG-CSF. In a number of immature bone marrow cells Y-25510 has a potent stimulatory effect on the recovery from the decrease in number of hematopoietic cells, keeping a balance in number of each blood cell.

Adjuvants, Immunologic↗

A revised method of conservative palatoplasty.

A revised method of conservative palatoplasty was performed on 21 patients with isolated cleft palate. The operation was principally based on von Langenbeck's method. The major modifications were that the mucosal layer was dissected instead of the mucoperiosteum and lateral mucosal deficits produced by medial displacement of the dissected mucosal flaps were covered with transpositioned buccal mucosal flaps. Postoperative early results were compared with those of the 23 patients treated by Perko's mucosal flap operation. Our method was found to bring about a relatively long velum comparable to Perko's method and wound healing was more uneventful. Results at the age of 5 years were compared with those of the patients treated by Wardill's mucoperiosteal flap operation as well as with those treated by Perko's method. There were no statistically significant differences among the three groups in the maxillofacial development and speech results.

Child, Preschool↗

Severe type Hunter's syndrome. Polysomnographic and neuropathological study.

The clinico-pathological and polysomnographical findings of an adult male patient with severe type of Hunter's syndrome are presented. He died of respiratory failure aged 19, which was much older than the average in this disease. Mucopolysaccharidosis was suspected at the age of one year, and diagnosed by leucocyte enzyme assay at 4 years of age. Mental and physical activity gradually deteriorated until his death. He often showed central type sleep apnea during the sleep stage 2, in addition to common obstructive apnea in Hunter's syndrome. The autopsy showed marked fibrous thickening of the endocardium and valves, enlargement of the liver and spleen, dilatation of the lateral ventricles and diffuse atrophy of the brain. Histologically, diffuse cytoplasmic vacuolations were found in fibroblast-like cells in the thickened endocardium and vascular walls, in Kupffer cells, and in many neurons of the central and peripheral nervous systems. Most neuronal inclusions were considered to be a ganglioside, and in other cells to be a mucopolysaccharide, by their ultrastructure. Massive accumulation of ganglioside in the neurons in the respiratory center might be reflected on central type sleep apnea.

Adult↗

Intraarterial infusion chemotherapy with [Sar1,Ile8]angiotensin II for bladder cancer.

Thirty-three patients with primary bladder cancer (nine stage T1 with multifocal tumors and 24 stage T2-4) were treated with intraarterial infusion chemotherapy including cisplatin, doxorubicin, and [Sar1,Ile8]Angiotensin II(AT II). Of the 32 evaluable patients, 12 had pathologically proven complete response (CR), 19 showed partial response (PR), and one showed no change (NC); the overall response rate (CR + PR) was 97%. The blood pressure increased in response to the administration of [Sar1,Ile8]AT II in all the patients; the mean increase in the systolic blood pressure was 36 mmHg. Most of the side effects were mild to moderate in severity, transient in nature, and included nausea/vomiting (100%), alopecia (84%), leukopenia (66%), headache (9%), nephrotoxicity (6%), diarrhea (3%), skin pigmentation (3%), and neurotoxicity (3%). One patient who dropped out of the study developed hemiplegia as a result of cerebral infarction. The findings indicate that it is necessary to exercise caution in selecting the patients to be subjected to this therapy. We conclude that intraarterial infusion chemotherapy combined with a vasoconstrictor has a significant effect not only against multifocal superficial bladder cancer but also against invasive bladder cancer.

1-Sarcosine-8-Isoleucine Angiotensin II↗

A pertussis toxin-sensitive mechanism of endothelin action in porcine coronary artery smooth muscle.

1. Endothelin-1 (ET-1)-induced contraction of porcine coronary artery strips may be mediated via at least two intracellular signalling mechanisms, the activation of dihydropyridine-sensitive voltage-dependent Ca2+ channels and the stimulation of phosphoinositide breakdown. Here we have investigated the possible involvement of pertussis toxin (PT)-sensitive guanosine-5'-triphosphate (GTP)-binding proteins (G-proteins) in ET-1-induced activation of these two signalling pathways in porcine coronary artery smooth muscle. 2. Increase in extracellular K+ concentration (10, 15 mM) shifted the dose-response relationship for the ET-1-induced contraction to the left. 3. The dihydropyridine Ca2+ channel blocker, nifedipine (10(-8) M), induced a rightward shift in the dose-response curve for ET-1. Pretreatment of the arterial strips with PT (0.1 microgram ml-1) induced a similar rightward shift of the ET-1 dose-response curve but not of the KCl response. Nifedipine (10(-8) M) did not further attenuate the ET-1-induced contraction in the PT-pretreated strips. 4. The pretreatment with PT significantly reduced 45Ca2+ uptake of the arterial strips stimulated by ET-1, but had no effect on ET-1-induced production of inositol phosphates. 5. The contractile response of the arterial strips to phorbol dibutyrate, an active phorbol ester, was not significantly affected by 10(-8) M nifedipine. 6. We confirmed that the pretreatment of the tissue with PT induced ADP-ribosylation of a 41 kDa membrane protein. 7. These findings indicate that activation of dihydropyridine-sensitive voltage-dependent Ca2+ channels by ET-1 in this tissue is mediated via a PT-sensitive G-protein in a manner apparently independent of the ET-1-induced activation of protein kinase C. It is concluded that the action of ET-1 in porcine coronary artery is mediated via two distinct signal transduction pathways, which are coupled to PT-sensitive and PT-insensitive GTP-binding proteins, respectively.

Adenosine Diphosphate Ribose↗

Effects of endothelin-1 and conversion of big endothelin-1 in the isolated perfused rabbit lung.

We examined the effects of endothelin-1 (ET-1) on pulmonary hemodynamic and transvascular fluid filtration and the conversion of big endothelin-1 (big ET-1), a precursor of ET-1, in isolated perfused rabbit lungs at constant vascular and airway pressures. Furthermore we examined whether ET-1 contributes to cyclooxygenase metabolism. The perfusate flow decreased significantly after bolus administration of 1 or 0.1 nmol of ET-1. Lung weight did not increase throughout the experimental period. Big ET-1- (1 nmol) induced decrease in the flow was slow in developing, although the maximum response was comparable to that induced by the same dose of ET-1. The concentration of bit ET-1 in the perfusate progressively decreased, while that of ET-1 increased in a time-dependent manner. Phosphoramidon, an inhibitor of metalloproteinase, suppressed the pressor effect of big ET-1 (P less than 0.01) and the increase in the concentration of ET-1 in the perfusate (P less than 0.05). The present findings provide the first evidence suggesting that the potent vasocontractile effect of big ET-1 in pulmonary circulation can be attributed to the production of ET-1 by the conversion from big ET-1 in the vascular bed. ET-1-induced perfusate flow changes were not affected by indomethacin, and the concentration of 6-ketoprostaglandin F1 alpha, a metabolite of prostacyclin, did not increase after ET-1 administration.

Animals↗

Correlation between the expression of P-glycoprotein and multidrug-resistant phenotype in transitional cell carcinoma of the urinary tract.

The expression of a multidrug-resistant (MDR) gene product, P-glycoprotein, was examined immunohistochemically in 41 transitional cell carcinomas (TCCs) of the urinary tract. In 23 of these, chemosensitivity to adriamycin (ADM) and vinblastine (VBL) was also assessed by a microtiter succinate dehydrogenase inhibition test and the correlation between the expression of P-glycoprotein and MDR phenotype was investigated. P-glycoprotein was detected in 13 (72.2%) of the 18 untreated TCCs of the upper urinary tract (UUT), 6 (31.6%) of the 19 untreated TCCs of the bladder, and all of the 4 TCCs treated with M-VAC chemotherapy, respectively. Fourteen (87.5%) of the 16 TCCs with a positive expression of P-glycoprotein were resistant to ADM and VBL, whereas all of the 4 TCCs sensitive to both drugs were negative in the expression of P-glycoprotein. The succinate dehydrogenase activity of TCCs with a positive expression of P-glycoprotein was significantly higher than that of TCCs with a negative expression of P-glycoprotein (P < 0.05). Thus, there was a good correlation between the expression of P-glycoprotein and MDR phenotype in the chemosensitivity test. These results suggest that intrinsic MDR exists in some TCCs of the urinary tract, particularly UUT, and that the immunohistochemical investigation of P-glycoprotein may be useful for predicting the MDR phenotype in TCCs of the urinary tract.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[Molecular pharmacology of endothelin in the cardiovascular system].

Endothelin-1 (ET-1), ET-2 and ET-3 are 21-amino acid peptides that act to stimulate contraction of many smooth muscle tissues including blood vessels, uterus, bladder, and intestine. In the case of each ET, the 21-amino acid bioactive form is produced from each precursor (referred to as big ET) via specific conversion between Trp-Val (ET-1, ET-2) or Trp-Ile (ET-3). Northern blot analysis of the mRNA for the ET isoform as well as determination of the peptide itself revealed that they are independently expressed in various tissues, indicating that each isoform may play separate physiological or pathophysiological roles. However, the vascular endothelial cells appear to produce only ET-1. Since ET-1 was first discovered, the majority of investigations so far reported have been concerned with this particular peptide. This review will focus on ET-1 with respect to the regulation of its biosynthesis in endothelial cells and its precise pharmacological actions on the cardiovascular system including the cerebral, coronary and renal circulations. Sub-classification of ET receptors was made from molecular biological, biochemical as well as pharmacological points of view. The signal transduction for mechanisms of action was also explained in detail.

Animals↗

Co-culture of in vitro fertilized bovine embryos with different cell monolayers.

The effects of different cell monolayers on in vitro development of early bovine embryos derived from in vitro maturation and fertilization were examined in this study. Early embryos (four to eight cells) were randomly allocated to bovine granulosa cell (GC), oviductal cell (OC), or uterine cell (UC) monolayers in Exp. 1 and to GC, skin cell (SC; from 10-d-old chicken embryos), testicular cell (TC; from 10-d-old mouse), and liver cell (LC; from 10-d-old chicken embryos) monolayers in Exp. 2, and cultured for 6 d at 38.6 degrees C in a humidified atmosphere of 5% CO2 in air. The culture medium was 12.5 mM HEPES TCM 199 supplemented with 1% calf serum and 1 mM sodium pyruvate. In Exp. 1, the percentage of four- to eight-cell embryos that developed to blastocysts on GC, OC, and UC monolayers was 26.9 (28/104), 37.5 (39/104), and 39.2 (40/102), respectively. In Exp. 2, the percentage of four- to eight-cell embryos that developed to blastocysts on GC, SC, TC, and LC monolayers was 53.3 (40/75), 42.9 (33/77), 49.3 (37/75), and 44.3 (35/79), respectively. There were no significant differences in development among groups in either experiment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Clinical effects of six-month short time biofiltration].

The clinical effects of six-month short time biofiltration (SBF) were evaluated using a B-A-B' study (B, B': conventional bicarbonate hemodialysis; CBHD, A:SBF) in ten patients maintained on CBHD three times a week. An F80 hemodiafilter (1.9 m2, polysulfone, Fresenius) was used. In addition to routine clinical parameters for a patient on regular dialysis treatment, plasma von Willebrand factor antigen (vWF) (an index of stimulation of vascular endothelium), and the methylguanidine/creatinine ratio (MG/Cr) and malondialdehide (MDA) (indices of the levels of oxygen radicals), were evaluated. Nine patients completed the study, one patient dropping out at the 12th week of A because of muscle cramps during SBF. The treatment time was 2 hours in six cases and 2.5 hours in three cases. The mean blood flow rate was 280 +/- 42 (SD) minutes. Using the urea kinetics model, the mean KT/V was 1.26 +/- 0.28, and the mean protein catabolic rate was 1.22 +/- 0.18 g/kg body weight/day at the end of A. No change in ultrafiltration, blood pressure, cardiac function (assessed by echocardiography), CTR, human atrial natriuretic peptide, total protein, albumin, uric acid, serum creatinine, sodium, calcium, inorganic phosphorus, vWF, or MDA was found between each period. Blood urea nitrogen, c-PTH, and MG/Cr increased during the A period. Serum magnesium and beta-2 microglobulin decreased during the A period. Blood gas results, on the whole, did not change. In a patients, however, acidosis gradually developed. An increase in substitution fluid from 5 L/session to 7.5 L/session improved the acid-base balance in that patient. In conclusion, SBF is as effective as CBHD in removing small molecules and maintaining cardiocirculatory status, and is superior to CBHD in removing beta 2-microglobulin and is less stimulative to the endothelium than CBHD.

Adult↗

[Clinical evaluation of operative and non-operative treatment in hepatocellular carcinoma with main portal vein tumor thrombus].

It has been well recognized that results of treatment in hepatocellular carcinoma with main portal vein tumor thrombus (Vp 3 HCC) are very poor. But we tried aggressive transcatheter treatment (one shot or continuous hepatic arterial infusion, TAE) and hepatectomy with postoperative TAE in 52 cases by Vp3 HCC in recent 10 years. Analysis of the results disclosed that PR or CR cases were observed only in the series of continuous hepatic arterial infusion therapy. And cumulative survival rate was the best in the series of hepatectomy (50% survival interval is 18 months). We concluded that hepatectomy and resection of the tumor thrombus with postoperative TAE is the best treatment in Vp3 HCC.

Antineoplastic Combined Chemotherapy Protocols↗

Sequence analysis and molecular detection of mouse hepatitis virus using the polymerase chain reaction.

Sequence analysis of the nucleocapsid protein genes of five strains of mouse hepatitis virus (MHV) disclosed that the 3' region of the nucleocapsid protein gene contains highly conserved sequences unique to MHV. We designed a pair of primers to amplify cDNA from such sequences of MHV by using the polymerase chain reaction (PCR). Six isolates of wild-type MHV, as well as prototype viruses, were amplified successfully and detected in ethidium bromide-stained agarose gels. The sequence identity of PCR products was readily verified by confirming target size and a MflI site within the target. The sensitivity of our PCR assay was estimated to be sufficient to detect a single cell infected with MHV. This new approach may permit more sensitive and rapid detection of MHV in biologic materials than current methods such as virus isolation, the infant mouse bioassay, and the mouse antibody production test.

Base Sequence↗

[Quantification of electroencephalogram continuity by 24-hour recording in very premature infants].

We aimed to quantify electroencephalogram (EEG) continuity for 24 hours in very premature infants. A total of 122 days of continuous two-channel EEG recordings were performed in 28 premature infants from 26 to 33 weeks of conceptional age (CA). None of the infants showed any evidence of neurological impairments during the course of their hospitalizations and showed normal neurological outcome. The 24-hour EEG recording was divided into 5.5-minute periods. The EEG of each period was classified into five EEG categories according to EEG continuity, and the percentage of each of them during the 24-hour recording was calculated. The percentages of continuous and continuous dominant EEG categories were increased with increasing CA. On the other hand, the percentages of discontinuous and discontinuous dominant EEG categories were decreased with increasing CA.

Electroencephalography↗

[A case of aspirin-induced asthma due to ketoprofen adhesive agent].

A 40-year-old woman who had been diagnosed as having aspirin-induced asthma was admitted with stridor. She had a history of surgery for sinusitis and nasal polyps, and severe asthmatic attack requiring mechanical ventilation after administration of puranoprofen (Niflan). On the second day of hospitalization, she used a ketoprofen adhesive agent (Miltax, 30 mg) for a stiff shoulder. Stridor developed five hours later, progressing to a severe asthmatic attack with loss of consciousness, requiring mechanical ventilation. The serum level of ketoprofen was very high (81.7 ng/ml); therefore, provocation challenge test was performed to confirm the possible relationship between the ketoprofen adhesive agent and asthmatic attack. After closed patching of the agent (15 mg) on her lower leg, stridor developed, and FEV1.0 and PFR decreased, in association with an increase of the serum level of ketoprofen to a maximum of 38.0 ng/ml. These results show that the topical application of a ketoprofen adhesive agent induced the asthmatic attack by transdermal absorption in this patient.

Adult↗