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Biomedical subjects

H Inoue

Publications and source records attributed to H Inoue.

At least 1,207 records · Page 67Linked to original sources

Surgical resection of a second primary lung carcinoma in a survivor of small cell carcinoma.

Resection of a second primary lung carcinoma in a long-term survivor of small cell lung carcinoma is reported. The patient had adenocarcinoma as the second primary tumor and underwent lobectomy with mediastinal node dissection. He was alive 99 months after the initial diagnosis of small cell carcinoma and 54 months after curative pulmonary resection for his second primary carcinoma.

Adenocarcinoma↗

Study on the suppressive effect of iodine-enriched egg on LT-C4 production in arachidonic acid-induced ear inflammation.

The anti-inflammatory mechanism of iodine-enriched egg was investigated in mice by means of arachidonic acid-induced ear inflammation. The lipid fraction of iodine-enriched egg was capable of suppressing the increase in ear weight induced by arachidonic acid in a dose-dependent manner. The lipid fraction was further separated into neutral and polar lipid fractions. Of these two fractions, only the neutral lipid fraction was capable of suppressing LT-C4 production in arachidonic acid inflammation. Neither the neutral nor polar lipid fractions of ordinary egg, however, showed any anti-inflammatory effect. These results suggest that the anti-inflammatory activity of iodine-enriched egg is present in the neutral lipid fraction, and its mechanism is assumed to be inhibition of LT-C4 production.

Animals↗

Study on the metabolism of lyso-platelet activating factor (lyso-PAF) in human paranasal sinus mucosa. The cultured ciliated epithelium can convert lyso-PAF to PAF.

The conversion of lyso-platelet activating factor (lyso-PAF) to PAF in cultured paranasal sinus mucosa obtained from normal human subjects was studied. The PAF concentration in the medium was determined after addition of lyso-PAF. PAF became detectable at 10 minutes after the addition of 10(-8)M lyso-PAF, and reached a maximum concentration (3.25 x 10(-9)M) at 20 minutes. The PAF level then gradually declined to become undetectable at 60 minutes after addition of lyso-PAF. Thus PAF is very unstable having a half-life calculated to be 12.8 minutes with an elimination constant of k = 0.05377 minutes-1. In contrast, lyso-PAF is known to be a stable metabolite of PAF as well as a precursor of PAF. The results obtained from this study suggest that the turnover of lyso-PAF to PAF may play a role in evoking prolonged inflammation in target organs or tissues.

Cells, Cultured↗

Detection of endothelin 1,2 and endothelin-like immunoreactant in wound surface and plasma in mice with thermal injury.

Endothelin is a well known vasoconstrictive peptides produced by endothelial cells and has been reported to regulate the systemic circulation. The authors investigated changes in endothelin in plasma and the surface of wounds induced with thermal injury using an experimental ear burn model in mice. At 0, 15, 30, 60, 120 and 180 minutes after thermal injury the plasma endothelin-like immunoreactant levels were 1.50 +/- 0.21, 1.86 +/- 0.36, 2.81 +/- 0.55, 2.62 +/- 0.27, 1.54 +/- 0.14 and 1.25 +/- 0.19 fmol/ml (N = 8), respectively. Endothelin-like immunoreactant levels in the plasma increased gradually until 30 minutes after the thermal injury. Endothelin-like immunoreactant content in the ear before thermal injury and at 60 minutes after injury were 7.04 +/- 0.64 and 8.61 +/- 1.24 fmol/ear (N = 8), respectively. The change in endothelin-like immunoreactant after thermal injury originated from endothelin 1,2; that is, the endothelin-1,2 content of the burned ear increased significantly 15 and 60 minutes after thermal injury to 12.52 +/- 0.68 and 11.58 +/- 1.04 fmol/ear, respectively, compared with 1.78 +/- 0.91 fmol/ear (N = 8) obtained before injury. These results suggested that endothelin 1,2 existed in the region of the wound caused by thermal injury.

Animals↗

Enhancer containing unusual GC box-like sequences on the human choline acetyltransferase gene.

The minimum requirement of an enhancer for the human choline acetyltransferase (ChAT) gene was analyzed by mutagenesis and protein-DNA interaction studies. A series of deletion and site-specific mutants were expressed transiently in a rat cholinergic neuroblastoma cell, NS20Y. The results revealed that the distal region between -970 and -941 base pairs (bp) from the transcription start site is essential for efficient transcription of the human ChAT gene. Two GC box-like sequences were located within this region, and they were shown to bind purified Sp1 transcription factor by footprinting and gel retardation analyses. This sequence, however, has an orientational effect and is located approximately 1000 bp from the transcription start site, unusual for the conventional GC box sequence. Furthermore, the sequence between these GC box-like sequences is shown to bind another novel trans-acting factor by gel retardation assay and to be necessary for efficient enhancer activity. On the other hand, gel retardation assays using a nuclear extract from Drosophila SL2 cells suggested that non-Sp1 trans-acting factors could also participate in the enhancing activity of this element. Taken together, the results demonstrate that two GC box-like sequences and another trans-acting factor-binding sequence located between -970 and -941 bp act coordinately and are essential for efficient transcription of this low expressed human ChAT gene.

Animals↗

Posterior interosseous nerve paralysis related to focal radial nerve constriction secondary to vasculitis.

A case of posterior interosseous nerve paralysis is reported with discussion of some characteristics that appear to distinguish it from entrapment neuropathy and neuralgic amyotrophy. The surgical implications are also discussed. More than ten similar cases have been reported, but the pathogenesis of this condition is still controversial. The patient presented with posterior interosseous nerve paralysis related to focal radial nerve constriction secondary to vasculitis in the perineurium. The constriction site was resected and the radial nerve was sutured. The patient recovered completely after 8 months.

Adult↗

Estimation of local vital reactions in severely burned tissues of guinea pig skin using C3a or C3a desArg as a marker.

We observed changes in levels of anaphylatoxin C3a and/or its desArg (C3a/C3a desArg) peptides in the local site of severely burned skin tissues of guinea pigs using immuno-Western blotting methods. The C3a/C3a desArg peptides, which were probably generated during complement activation, were detected at significant levels from 30 min to 72 h following burn injury in an area limited to 3 mm from the wound edge. Levels of these peptides showed a tendency to be highest in that area 24 h after burn infliction. In postmortem injuries, C3a/C3a desArg peptides could not be detected. These peptides were detected in antemortem wounds up to at least 2 days at 22 degrees C and up to 3 days at 4 degrees C after death, although decreases in levels were found. Lower concentrations of these peptides were also found in postmortem burns in which postmortem hypostasis appeared strongly. These results suggest that, except for injuries of the area with obvious postmortem hypostasis, detection of C3a/C3a desArg can be useful for estimation of vital reactions in many kinds of wounds during inflammation.

Animals↗

Parasympathetic activity is a major modulator of the circadian variability of heart rate in healthy subjects and in patients with coronary artery disease or diabetes mellitus.

Autonomic heart rate control was assessed by power spectral analysis of heart rate variability in 24-hour ambulatory electrocardiographic recordings from 23 healthy subjects, 14 patients with coronary artery disease without cardiac dysfunction, and 14 patients with diabetes mellitus. The log value of the ratio of the low-frequency component (LF = 0.04 to 0.15 Hz) to the high-frequency component (HF = 0.15 to 0.5 Hz) and logHF were employed as indexes of sympathetic and parasympathetic activity, respectively. Diurnal and nocturnal logLF, logHF, and log(LF/HF) values were calculated for heart rates of 60, 70, and 80 beats/min. Intergroup differences among these three variables were not significant at any heart rate. Although a heart rate-related decrease in logHF was generally observed, the relationship between log(LF/HF) and heart rate was not consistent. The correlation between diurnal and nocturnal logHF values was significant at all three heart rates (r = 0.63, 0.87, and 0.59), whereas the diurnal log(LF/HF) was correlated with the nocturnal value only at 70 beats/min (r = 0.77). These results suggest that the heart rate during normal daily activities is a reliable indicator of parasympathetic tone, if not sympathetic tone, in healthy subjects and patients with coronary artery disease or diabetes mellitus.

Aged↗

Relationship between distribution of hypertrophy and electrocardiographic changes in hypertrophic cardiomyopathy.

To assess the relationship between the distribution of hypertrophy and electrocardiographic changes in patients with hypertrophic cardiomyopathy, magnetic resonance imaging and ECG findings were correlated in 25 patients with apical hypertrophy (group I), 15 patients with both apical and basal hypertrophy (group II), and 11 patients with hypertrophy localized to the basal left ventricle (group III). The number of precordial leads with negative T waves (-0.5 mV or more) was greater in group I than in groups II and III (I = 3.0 +/- 1.5, II = 1.7 +/- 1.5, III = 0.3 +/- 0.6; p < 0.01). Giant negative T waves (-1.0 mV or more) in precordial leads were found in 13 patients (52%) in group I and five patients (33%) in group II but were not found in group III. In contrast, tall positive T waves (> or = 1.0 mV) in precordial leads were found in two patients (13%) in group II and five (45%) in group III but were not found in group I. These results suggest that the distribution of hypertrophy in patients with hypertrophic cardiomyopathy produces a particular T wave polarity in precordial leads.

Adult↗

Pure yolk-sac tumor of the lung.

The first case of a pure primary yolk-sac tumor of the lung is presented. The tumor developed in the right upper lobe of a 31-year-old man; preoperatively, the serum alpha-fetoprotein concentration was elevated. Treatment consisted of pulmonary segmentectomy with postoperative combination chemotherapy. The patient is alive and well 13 months after surgery with a normal serum alpha-fetoprotein concentration.

Adult↗

Transgenic Drosophila carrying mammalian cytochrome P-4501A1: an application to toxicology testing.

Transgenic Drosophila which carry a canine cytochrome P-450 were established and evaluated for its value on toxicology testing. Dah1, a cDNA clone for the canine hepatic P-4501A1, was ligated between the promoter of Drosophila heat-shock protein gene and the terminator of actin 5C gene, and then microinjected into Drosophila embryos with a transposon P element. The injected DNA was stably integrated into chromosomal DNA in germ line cells. After heat-shock treatments, transgenic larvae produced mRNA and a detectable amount of protein that cross-reacted with antibodies against rat P-4501A1. The ability of transgenic flies to activate procarcinogens was monitored in the DNA repair test with the endpoint being preadult mortality of repair-defective mei-9a mei-41D5/Y males. Heat-shock treatments of larvae showed that the repair-defective males carrying the P-4501A1 transgene were killed by lower concentrations of 7,12-dimethylbenz[a]anthracene than their non-transgenic or non heat-shocked counterparts. Coadministration of alpha-naphthoflavone, one of the inhibitors of P-4501A subfamily, cancelled the enhanced mortality of transgenic males, supporting that 7,12-dimethylbenz[a]anthracene was metabolized to its genotoxic form by the expressed P-4501A1 enzyme. This study indicates a potential utility of transgenic Drosophila for screening mammalian promutagens and procarcinogens.

9,10-Dimethyl-1,2-benzanthracene↗

Structural study of the N-linked oligosaccharides of hepatocyte growth factor by two-dimensional sugar mapping.

The structures of the N-linked oligosaccharides on recombinant human hepatocyte growth factor (rh-HGF) expressed by Chinese hamster ovary (CHO) cells were studied by two-dimensional sugar mapping. The oligosaccharides released from the glycopeptides by peptide: N-glycosidase F (PNGase F) treatment were tagged with 2-aminopyridine at the reducing ends. The alpha-chain was linked by biantennary, triantennary, and tetraantennary oligosaccharides, but the dominant oligosaccharides linking the beta-chain were biantennary (> 85%). There was no significant difference in oligosaccharide structures between the two glycosylation sites on each chain, that is, Asn263 and Asn371 on the alpha-chain, and Asn535 and Asn622 on the beta-chain. The linkage of sialic acid to the non-reducing terminal galactose was identified as NeuAc alpha(2-3) by 1H-NMR spectrometry. The structures of the N-linked oligosaccharides from rat HGF were also studied. Triantennary oligosaccharides were obtained from the alpha-chain and a biantennary oligosaccharide was obtained from the beta-chain. This result indicates that the alpha-chain is also linked by higher branched oligosaccharides than the beta-chain in rat HGF.

Aminopyridines↗

Site-directed mutagenesis study on the roles of evolutionally conserved aspartic acid residues in human glutathione S-transferase P1-1.

The evolutionally conserved aspartyl residues (Asp57, Asp98 and Asp152) in human glutathione S-transferase P1-1 were replaced with alanine by site-directed mutagenesis to obtain the mutants (D57A, D98A and D152A). The replacement of Asp98 with alanine resulted in a decrease of the affinity for S-hexyl-GSH-agarose, a 5.5-fold increase of the KmGSH and a 2.9-fold increase of the I50 of S-hexyl-GSH for GSH-CDNB conjugation. Asp98 seems to participate in the binding of GSH through hydrogen bonding with the alpha-carboxylate of the gamma-glutamyl residue of GSH. The kcat of D98A was 2.6-fold smaller than that of the wild-type, and the pKa of the thiol group of GSH bound in D98A was approximately 0.8 pK units higher than those in the wild-type. Asp98 also seems to contribute to the activation of GSH to some extent. On the other hand, most of the kinetic parameters of D57A and D152A were similar to those of the wild-type. However, the thermostabilities of D57A and D152A were significantly lower than that of the wild-type. Asp57 and Asp152 seem to be important for maintaining the proper conformation of the enzyme.

Amino Acid Sequence↗

Antifibrillatory effects of class III antiarrhythmic drugs: comparative study with flecainide.

The antifibrillatory effects of flecainide 1 mg/kg + 0.05 mg/kg/min intravenously (i.v.), bretylium 6 mg/kg i.v., D-sotalol 2 mg/kg + 0.1 mg/kg/min i.v., and E-4031, a new class III drug, 50 micrograms/kg + 5 micrograms/kg/min i.v. were compared with three different methods of determining ventricular fibrillation threshold (VFT) in anesthetized open-chest dogs. In protocol 1, VFT was determined with 2-S, 50-Hz continuous pulses. Flecainide (n = 7) prolonged intraventricular conduction time (CT) and ventricular effective refractory period (ERP) and increased VFT significantly. Bretylium (n = 6) prolonged ERP slightly, but did not increase VFT significantly. Both D-sotalol (n = 6) and E-4031 (n = 6) prolonged ERP and increased VFT. In protocol 2, VFT was determined with the extrastimulus technique in dogs, with localized ventricular necrosis produced with protease. Flecainide (n = 10), D-sotalol (n = 8), and E-4031 (n = 8) restored VFT, which had been decreased by protease injection, to the baseline level, whereas bretylium (n = 8) did not. In protocol 3, the train pulse method with 100-Hz train pulses covering the vulnerable period was used in the same dogs used for protocol 2. Flecainide, bretylium, and D-sotalol increased VFT, but E-4031 did not. The antifibrillatory effects of class III drugs differ depending on the method of VFT determination. The present data suggest that the antifibrillatory effects of antiarrhythmic drugs should be assessed by different methods of VFT determination.

Analysis of Variance↗

Selective exclusion of the injured lung.

Intratracheal bleeding and intrapleural air leakage that are uncontrollable by conventional therapy are life-threatening in patients with blunt pulmonary trauma. Selective exclusion of the injured lung is the most effective treatment in such cases. Two hundred six consecutive patients over a 5-year period with blunt pulmonary trauma who survived 5 hours or more after arriving at the hospital were divided into three categories based on mode of treatment. In 190 (92%), intratracheal bleeding, intrapleural air leakage, and intrapleural bleeding were controllable by conventional treatment (class 1). In six (3%), intratracheal bleeding and intrapleural air leakage were controllable by selective pulmonary exclusion, and intrapleural bleeding was controllable by tube thoracostomy (class 2). In ten (5%), thoracotomy was required because of uncontrollable intratracheal bleeding or intrapleural air leakage, despite selective pulmonary exclusion, or intrapleural hemorrhage was not controllable by tube thoracostomy (class 3). Among the 16 patients with class 2 or 3 trauma, 14 survived.

Adolescent↗

Growth factor-induced process formation of megakaryocytes derived from CFU-MK.

The extended cytoplasmic processes from megakaryocytes (MK) are believed to be structural intermediates between MK and platelets. We could observe differentiation of purified rat CFU-MK toward mature MK to form extended cytoplasmic processes. Recombinant rat interleukin-3 (IL-3), human erythropoietin (Epo), and human interleukin-6 (IL-6) each was able to stimulate process formation although they varied somewhat in their potential. Electron microscopic observations showed that these processes were very similar to those from mature MK so far reported. The combination of IL-6 with IL-3 or Epo synergistically increased the number of MK forming processes without further increase in the number of total MK formed in the presence of IL-3 or Epo alone. In addition, IL-6 significantly increased the megakaryocytic diameter and DNA content of MK induced by IL-3 or Epo and shortened the MK transit time to hasten the process formation of MK. These findings suggest that IL-6 promotes further maturity in both the cytoplasm and ploidy of MK to form extended cytoplasmic processes. The ability of these factors to generate the process formation in vitro may be related to their thrombopoietic effects in vivo.

Animals↗

Immunofluorescence imaging diagnosis of Fabry heterozygotes using confocal laser scanning microscopy.

An immunofluorometric method was developed for the semiquantitative determination of trihexosylceramide in cultured fibroblasts from Fabry disease patients, using a laser scanning confocal imaging system. The accumulated glycolipid was detected as granular inclusions in the cells. Heterozygote identification was achieved both by counting of immunoreactive cells and by measuring the relative fluorescence intensity with a digital imaging system.

Adult↗