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Biomedical subjects

S Sato

Publications and source records attributed to S Sato.

At least 19 recordsLinked to original sources

Different sensitivities of human esophageal cancer cells to multiple anti-cancer agents and related mechanisms.

Mechanisms responsible for drug resistance in human esophageal cancer cell lines were investigated. Three cell lines established from human esophageal carcinoma (TE-1, SH-1, and TH) showed different sensitivities to vindesine, vincristine, cisplatin (CDDP), etoposide (VP-16), and pepleomycin. Both SH-1 and TH cell lines were twofold to sevenfold more resistant to pepleomycin, vindesine, and vincristine than TE-1 was. SH-1 showed twofold more resistance to CDDP than either TE-1 or TH did, and TH and TE-1 showed a 3-fold or 1.5-fold more resistance, respectively, to VP-16 than SH-1 did. The accumulation of tritiated vincristine in SH-1 and TH was approximately 50% that in TE-1. Two multidrug resistance reversal agents, cepharanthine and a synthetic dihydropyridine analogue (NK-252; Nikken Chemicals, Saitama, Japan), potentiated the cytocidal actions of vindesine against SH-1, TH, and TE-1 cells, with no apparent expression of P-glycoprotein in the three cell lines. The glutathione S-transferase pi gene was expressed in all three cell lines. DNA topoisomerase II levels were lowest in TE-1, followed by SH-1 and TH, although the accumulation of tritiated VP-16 was less in both TH and SH-1 than in TE-1. Differential sensitivities to anti-cancer drugs appear to be mediated through pleiotropic mechanisms.

ATP Binding Cassette Transporter, Subfamily B, Mem

[Hepatic arteriography under temporary hepatic venous occlusion].

Hepatic arteriography with and without temporary segmental hepatic vein occlusion was performed in 10 patients, five of whom had chronic liver injury. Hepatic arteriograms obtained during hepatic venous obstruction demonstrated significantly more peripheral and definite arterial branches in the occluded area and fewer peripheral branches in the non-occluded segment. A prolonged, dense hepatogram (sinusoidogram) showing hepatofugal opacification of the portal vein was obtained in the occluded area. Only one case with a large veno-venous anastomosis did not show these findings. Hepatic arteriograms in two cases with hepatocellular carcinoma provided clear visualization of peripheral portal branches that could act as efferent tumor vessels during regional temporary hepatic vein occlusion. Temporary hepatic venous occlusion may cause a sudden increase of hepatic arterial flow in the occluded area and transsinusoidal arterioportal communication there. This method can be useful for the diagnosis and arterial infusion or embolization therapy of hepatic diseases.

Adult

Distributions of heat shock protein (HSP) 70 and heat shock cognate protein (HSC) 70 mRNAs after transient focal ischemia in rat brain.

The distribution of heat shock protein (HSP) 70 and heat shock cognate protein (HSC) 70 mRNA after 30 min of middle cerebral artery (MCA) occlusion was investigated in rat brain by in situ hybridization using cloned cDNA probes selective for the mRNAs. While HSP70 mRNA was hardly present at caudate and dorsal hippocampal levels of the sham brain this mRNA was greatly induced in cells of the MCA territory 1 h after reperfusion. Although the maximum amount of induced HSP70 mRNA in the caudate was much smaller than that in the cortex the maximum induction in the caudate (3 h) preceded that in the cortex (8 h). In contrast to the case of HSP70 mRNA, HSC70 mRNA was present in most cells of the sham brain, and was especially dense in hippocampal CA3 cells. Further induction of HSC70 mRNA was observed after reperfusion in the same cell populations, as in the case of HSP70 mRNA. HSC70 mRNA levels were significantly reduced in the caudate at 8 h when small amounts of HSP70 mRNA were still elevated. In the ipsilateral granule cells of the dentate gyrus and hippocampal CA3 cells a slight but significant induction of HSC70 mRNA was observed from 1 h to 1 day, while obvious induction of HSP70 mRNA never occurred. All the induced signals of HSP70 and HSC70 mRNA were diminished or returned to the sham level by 7 days, except for HSC70 mRNA in the caudate. These results are the first observations of the distribution of HSP70 and HSC70 mRNA after transient focal ischemia of rat brain.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

A novel note on the effect of ara-C on the polyamine content of the male accessory organs of the rat.

The effects of 1-beta-D-arabinosylcytosine (ara-C) given for 5 days on body weight, on the weights of the prostate, seminal vesicles and testis, and on the polyamine content (putrescine, put; spermidine, spd; spermine, spm) in these organs were examined in rats. The body weights of the ara-C-treated rats showed a decrease of 13% (P less than 0.01) and the weights of the prostate, seminal vesicles and testis were reduced by 20% (P less than 0.05), 13% and 5.0% (P less than 0.1), respectively. However, put, spd and spm contents in the ara-C-treated prostate were increased 1.2, 1.8 and 2.9 times, respectively. The contents of these polyamines in the ara-C-treated seminal vesicles increased about 40% for all polyamines. Both spd and spm in the treated testis showed a significant increase of about 20% (P less than 0.05) as compared with the control. In addition, the total polyamines in the whole organs increased significantly in both the prostate and testis.

Animals

New antiinflammatory agents. 2. 5-Phenyl-3H-imidazo[4,5-c][1,8]naphthyridin-4(5H)-ones: a new class of nonsteroidal antiinflammatory agents with potent activity like glucocorticoids.

We previously described new antiinflammatory agents, 4-hydroxy-2-oxo-1-phenyl-1H-1,8-naphthyridine-3-carboxamides 1. Further modification of the compounds bearing 1-phenyl-1,8-naphthyridin-2-one as a mother skeleton led to 5-phenylimidazo[4,5-c][1,8]naphthyridin-4(5H)-one derivatives 2 and 3. Regioselective synthesis of these compounds bearing a substituent at the 1- or 3-position was conducted according to the method shown in Schemes I and II. In this series of compounds, antiinflammatory activities were greatly influenced by the position and nature of substituents on imidazole. 3-Alkyl or 3-benzyl substitution result in the potent activity, but 1-substitution did not. Minor modification of the benzyl group reduced or eliminated the activity. Detailed examination of structure-activity relationships led to 3-benzyl-5-phenyl-3H-imidazo[4,5-c][1,8]naphthyridin-4(5H)-one (22), which exhibited potent oral antiinflammatory activities in carrageenan-, zymosan-, and reversed passive Arthus reaction-induced rat paw edemas (ED40 = 5.3, 0.37 mg/kg, ED50 = 0.47 mg/kg, respectively). This broad activity of 22 was like that of glucocorticoids. Compound 22 did not affect activities of CO and 5-LO enzymes and receptor binding of various ligands. As one of the mechanisms of action, induction of release of glucocorticoids was postulated. These results suggest that 22 represents a novel class of antiinflammatory agents.

Animals

Experimental atrophic rhinitis in 2 and 4 month old pigs infected sequentially with Bordetella bronchiseptica and toxigenic type D Pasteurella multocida.

Experimental infections with Bordetella bronchiseptica and/or toxigenic type D Pasteurella multocida were studied in 2- and 4-month-old primary specific-pathogen-free pigs. None of the 2-month-old pigs inoculated with B. bronchiseptica or P. multocida alone developed turbinate atrophy. All the pigs inoculated with B. bronchiseptica (10(7) CFU/head) and P. multocida (10(9) CFU/head for 5 consecutive days) together, however, developed clinical and post-mortem signs of atrophic rhinitis (AR) similar to the naturally occurring disease. Slight to severe turbinate atrophy was observed in the 4-month-old pigs inoculated with B. bronchiseptica and P. multocida (at the same concentration as above) at necropsy.

Animals

Binding specificity of a baby hamster kidney lectin for H type I and II chains, polylactosamine glycans, and appropriately glycosylated forms of laminin and fibronectin.

The carbohydrate binding specificity of Mr = 30,000 lectin (CBP30) from baby hamster kidney (BHK) cells has been studied by inhibition of binding of the radiolabeled lectin to asialofetuin-Sepharose using model oligosaccharides and glycopeptides. CBP30 binds type I or II Gal beta(1----3(4))GlcNAc chains but not Gal(beta 1----3)GalNAc. The inhibitory potency of straight chain polylactosamine structures or complex-type branched glycans is increased in proportion to the number of Gal(beta 1----3(4)) units present. Fucosylation or sialylation of terminal galactose residues or further substitution by (alpha 1----3)-linked galactose or N-acetylgalactosamine does not affect binding whereas substitution of the penultimate N-acetylglucosamine residue drastically reduces binding. Thus, blood group A, H type I or H type II structures, shows high affinity whereas Lex, Lea, and Leb structures bind poorly. CBP30 binds to murine Engelbreth-Holm-Swarm (EHS) tumor laminin and human amniotic fluid fibronectin but not human plasma fibronectin. Binding involves polylactosamine glycans as well as tri- and tetraantennary complex-type glycans present in EHS laminin and amniotic fluid fibronectin but absent in plasma fibronectin. Proteolytic fragments of EHS laminin (E1X/Nd, P1, E8, and E3) bind CBP30, but only fragment E8 supports attachment and spreading of BHK cells. BHK cell adhesion to EHS laminin or fragment E8 was not disturbed by CBP30-specific antibodies, but at relatively high concentrations (45 micrograms/ml) CBP30 inhibited spreading and partially attachment of cells on laminin.

Acetylglucosamine

The human multidrug resistance 1 promoter has an element that responds to serum starvation.

We have previously demonstrated in transient expression assay systems that a human multidrug resistance 1 (MDR1) promoter can be directly activated by cytotoxic anticancer agents. In this study, we examined whether the MDR1 promoter could be regulated in response to growth arrest induced by serum starvation. We have established human and rodent cell lines which stably expressed the chloramphenicol acetyltransferase (CAT) gene driven by various lengths of the MDR1, the viral thymidine kinase (TK) and the simian virus 40 (SV40) promoters. Serum starvation caused enhanced expression of CAT gene with MDR1 promoter, but not with two viral gene promoters in human cancer KB cells. Hydroxyurea activated the MDR1 promoter, but not TK and SV40 promoters. By contrast, the DNA topoisomerase II inhibitor, etoposide, equally activated the MDR1, TK and SV 40 promoters. Increased CAT gene expression by serum starvation was also specifically observed in stable transfectants of human adrenal SW-13 cell lines, but not in stable transfectants of mouse fibroblast NIH3T3 and adrenal Y-1 cell lines when the human MDR1 promoter-CAT was introduced. Etoposide, however, effectively induced CAT activity in both human and rodent cells. Assays with deletion constructs of the MDR1 promoter showed that serum starvation activated the MDR1 promoter carrying -258 approximately +121 base sequence of the promoter, but not -198 approximately +121 of the promoter. These results suggest that the expression of the MDR1 gene induced by serum starvation is regulated at the transcriptional level in a promoter sequence-specific manner in human cells.

Animals

Estimation of right ventricular pressure in children by thallium-201 myocardial imaging using single-photon emission computed tomography.

Thallium-201 myocardial imaging using single-photon emission computed tomography was performed to estimate right ventricular (RV) systolic pressure in 34 children (aged 4.1 to 16.1 years, mean 7.9 +/- 2.9). Acquisition of the images was performed using a semicircular arc of 180 degrees. On a short-axis slice, a line drawn perpendicular to the ventricular septum so as to cross the RV free wall showing maximum uptake was defined as the region of interest. Thallium-201 counts in regions of interest over both RV and left ventricular (LV) free walls were measured. The ratio of RV-to-LV peak thallium-201 counts was compared with RV peak systolic pressure and the ratio of RV-to-LV peak systolic pressure measured at cardiac catheterization. Both RV peak systolic pressure and the ratio of RV-to-LV peak systolic pressure correlated well with the ratio of RV-to-LV peak thallium-201 counts (r = 0.95 and 0.96, respectively). The ratio of RV-to-LV peak thallium-201 counts greater than or equal to 0.45 could predict RV pressure overloading with a sensitivity of 92%, and a specificity of 88%. Thus, the quantitative analysis of thallium-201 myocardial imaging using single-photon emission computed tomography permits the noninvasive and accurate estimation of RV systolic pressure in children.

Adolescent

[CT-guided percutaneous lung biopsy using a cutting needle and an automated biopsy gun. Comparison with lung biopsy using a manual aspiration needle].

Twenty-five percutaneous lung biopsies using a 20-gauge cutting needle and automated biopsy gun (ABG) were performed under CT guidance in 25 patients with thoracic lesions. This procedure was compared with that using a 21-gauge manual aspiration needle in 36 patients (40 examinations, 37 lesions) in terms of success rate, rate of correct diagnosis, mean examination time and rate of complications. Specimens obtained from lung biopsy were graded by a histopathologist according to quality and quantity from 0 to 4 (pathological score). There were no statistically significant differences between the two procedures in terms of success rate, rate of correct diagnosis and rate of complications; only the time required was significantly different. However, sufficient biopsy material and a mean pathological score of G-II 2.8 (that of G-I was 1.9, p less than 0.05) could be obtained by the biopsy procedure using the cutting needle. The above results indicated that aspiration needle biopsy was adequate for lung biopsy, but that a cutting needle and ABG should be used when a good biopsy specimen is needed for tissue diagnosis.

Adolescent

Human carbonic anhydrase IV: cDNA cloning, sequence comparison, and expression in COS cell membranes.

We have isolated a full-length cDNA for human carbonic anhydrase IV (CA IV) from a lambda gt10 human kidney cDNA library. The 1105-base-pair (bp) cDNA contains a 47-bp 5' untranslated region, a 936-bp open reading frame, and a 122-bp 3' untranslated region. The deduced amino acid sequence is colinear with the N-terminal sequence and the sequence of several tryptic peptides of human lung CA IV. It includes an 18-amino acid signal sequence, a 260-amino acid region that shows 30-36% similarity with the 29-kDa cytoplasmic CAs (CA I, CA II, and CA III), and an additional 27-amino acid C-terminal sequence that ends in a 21-amino acid hydrophobic domain. Of the 17 "active site" residues that are highly conserved in other human CAs, 16 are also present in CA IV. Expression of the cDNA in COS cells produced a 35-kDa enzyme that was membrane associated, resistant to inactivation by SDS, contained no carbohydrate, and reacted on Western blots with antiserum to the 35-kDa CA IV from human lung. Treatment of membranes from transfected COS cells with phosphatidylinositol-specific phospholipase C released 20-30% of the expressed enzyme from membranes, indicating that at least 20-30% of the expressed enzyme was anchored to membranes by a glycosyl-phosphatidylinositol linkage.

Amino Acid Sequence

Temporal lobectomy for uncontrolled seizures: the role of positron emission tomography.

We evaluated the role of positron emission tomography (PET) with [18F]deoxyglucose (FDG) (FDG-PET) for planning surgery in 53 patients who had temporal lobectomy for uncontrolled seizures at National Institutes of Health from 1981 to 1990. Investigators blinded to PET data used results of telemetered video-electroencephalographic ictal monitoring and other standard criteria to decide whether subdural electrodes (22 patients, i.e., the "invasive" group) should be implanted or surgery performed. PET scans were analyzed using a standard regional template. Mean lateral but not mesial temporal asymmetry was significantly higher in patients who became seizure free (p < 0.03). Patients with > or = 15% hypometabolism were significantly more likely to be seizure free in the entire study population and the invasive subgroup. Visual identification of hypometabolism was less accurate. When a clear temporal ictal surface electroencephalographic focus was present, FDG-PET provided less additional information. FDG-PET may be particularly valuable if the surface electroencephalographic scan is nonlocalizing. In addition to helping to identify the seizure focus, it may allow limitation of invasive electrode placement to those necessary for functional mapping. When PET is used to identify epileptic foci, quantitative measurements of asymmetry should be made.

Brain

Severe acute axonal form of Guillain-Barré syndrome associated with IgG anti-GD1a antibodies.

We report cases of 2 patients with pure motor Guillain-Barré syndrome of explosive onset who required mechanical ventilation for more than 2 months. Their electrophysiologic findings and poor clinical recoveries suggested severe axonal degeneration involving the motor nerves. Enzyme-linked immunosorbent assay and thin-layer chromatogram-immunostaining showed the sera of both patients had high IgG antibody titer against GD1a ganglioside. Their titers decreased with the clinical course of the illness. GD1a as well as GM1, appears to be the target pathogenic antigen in motor axon disorders. Elevated IgG anti-GD1a antibody titer may prove useful for predicting severe GBS.

Acute Disease

Angiographic findings of ischemic stroke in children.

A cooperative study was undertaken in the Tohoku district of Japan to investigate the relatively rare phenomenon of cerebral infarction in children. The purpose of the present paper is to describe the cerebral angiographic findings in 48 children whose ischemic lesions were confirmed by CT scan. The majority of lesions were considered to be idiopathic. The areas of cerebral infarction appearing in the CT scans were located in the territory of the middle cerebral artery including the basal ganglia. Angiographical abnormalities were observed in 40 patients (83%). The majority occurred in the supraclinoid portion of the internal carotid artery and in the cisternal portion of the middle and anterior cerebral arteries. Multiple lesions, such as in the C1, A1, and M1 or the C1, M1, and M2 segments were observed in 22 cases. These lesions generally appeared in continuation; no bilateral intracranial lesions were observed. Repeated angiography was performed in 22 cases, and in 55% of these some recovery of the lesions was seen.

Cerebral Angiography

Cerebral blood flow and oxygen metabolism in infants with hydrocephalus.

In this study, regional cerebral blood flow (rCBF) and the cerebral metabolic rate of oxygen (rCMRO2) were measured using positron emission tomography (PET) with oxygen-15 radiopharmaceuticals to clarify the pathophysiology of ventriculomegaly in the developing brain. Four hydrocephalic infants without severe neurological deficit were studied. Hypoperfusion was observed in the frontal, parietal, and visual association cortices which surrounded dilated anterior or posterior horns of the lateral ventricle. Lower rCMRO2 values than adult rates were observed in all cases. In the infants with markedly enlarged anterior or posterior horns, the surrounding cortices showed relatively lower rCMRO2 values with the fall of rCBF. Postoperative studies were performed in two infants. rCMRO2 increased in every region after ventriculoperitoneal shunting, but little change was observed in rCBF. These results indicate that metabolic deterioration occurs in the developing brain with hydrocephalus.

Blood Volume

Evaluation of the measurement of the intraoperative transcutaneous partial pressure of oxygen (PtcO2) as a prognostic indicator in vascular reconstruction.

The intraoperative transcutaneous partial pressure of oxygen (PtcO2) was used to monitor 58 vascular reconstructive surgery procedures in 54 patients. The study comprised three groups: Group A (24 limbs without any ischemic symptoms or signs), Group B (45 limbs with intermittent claudication), and Group C (12 limbs with ischemic rest pain, ulceration, and gangrene). In addition in 31 patients the chest wall was monitored simultaneously as a control. The results showed that the PtcO2 values increased immediately and significantly to varying degrees and at varying speeds after unclamping. The controls had higher values than Group A (P > 0.05), Group B (P < 0.05), and Group C (P < 0.05) patients. Further study showed that there were no significant differences between the maximal values in the limbs with good distal vessel run-off in Groups A, B, and C, and in the controls (P > 0.05). It is thus concluded that effective vascular reconstruction in the limbs is indicated by a rapid and marked increase of both the PtcO2 value and the response value, while with a slow and low increase of the value, early graft failure and poor distal vessel run-off should be suspected. We believe that this monitoring method dynamically reflects the functional state during vascular reconstruction and is clinically valid.

Adult

A case of linitis plastica of the rectum treated by pelvic exenteration after aggressive immunochemotherapy.

Multidisciplinary treatment was administered to a 32 year-old man with primary linitis plastica of the rectum, which was considered inoperable due to an extensive local spread at the first operation. Thirty KE of OK-432 was injected into the tumor per week (total 90-KE) and 5 KE of OK-432 was inoculated into the intracutaneous space per week (total 125 KE). Also methotrexete (MTX 50 mg) and 5-FU (500 mg) combined were given each week by intra-arterial infusion (total 20 courses). After this immuno-chemotherapy the CEA decreased from the pretreatment value of 12.7 ng/ml to 3.6 ng/ml and the tumor size was reduced. A total pelvic exenteration could then be performed almost curatively. As a result, this patient was able to return to the society with a better quality of life and has survived for 20 months since presentation.

Adult

Calcitonin gene-related peptide (CGRP)-immunoreactive nerve plexuses in the renal pelvis and ureter of rats.

The distribution of calcitonin gene-related peptide-immunoreactive nerve fibers in the renal pelvis and ureter was examined by immunohistochemistry using whole-mount preparations and cryostat sections. The patterns of innervation were contrasted between the pelvis and ureter; the immunoreactive nerve fibers in the pelvis ran parallel to the long axis of each of the circular and longitudinal muscle layers, causing a lattice-like appearance of the nerve fibers. In the ureter, the immunoreactive fibers were accumulated in the subepithelial region and the longitudinal muscle. In both the pelvis and ureter, a portion of the nerve fibers of smaller caliber showed a swollen or beaded structure; they were located in the musculature and beneath the epithelium extending for considerable distances. Ligation of the ureter caused a marked decrease in the immunoreactive nerves in the pelvis and the proximal portion of the ureter, suggesting that the axonal flow in the calcitonin gene-related peptide-containing neurons of the ureter runs towards the pelvis.

Animals