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Biomedical subjects

C Inoue

Publications and source records attributed to C Inoue.

At least 73 records · Page 4Linked to original sources

[Treatment with sulbactam/cefoperazone of severe infections in patients with hematological disorders].

Infectious episodes in 90 patients with hematological disorders were treated with sulbactam/cefoperazone (SBT/CPZ), a new combination drug of a potent beta-lactamase inhibitor, sodium sulbactam, and a third generation cephalosporin, sodium cefoperazone. Clinical responses to the SBT/CPZ regimen were excellent in 23 cases, good in 30 cases, fair in 11 cases, and poor in 26 cases. The overall efficacy rate (percentage of cases showing excellent or good responses) was 58.9%. Efficacy rates classified according to different infections were: 80% in documented sepsis, 57.6% in suspected sepsis, 61.1% in pneumonia and 50% in other infections. One episode of side effect was encountered with redness and itching of skin. Hepatic disorders were observed in 3 cases. These adverse reactions, however, were not serious. These results indicate that SBT/CPZ has a high therapeutic efficacy to severe infections in patients with hematological disorders.

Adolescent↗

[Growth inhibition of erythroid colonies by autologous sera and the clinical effect of erythropoietin in chronic renal disease].

We investigated the inhibitory effect of autologous sera on erythroid colony formation (CFU-E) of bone marrow cells from patients with chronic renal disease and the clinical effect of recombinant erythropoietin. Colonies formed in cultures using autologous serum (AS) decreased in 15 among 30 cases as compared with those using fetal calf serum (FCS). This inhibitory effect of autologous sera was diminished by treatment with activated charcoal in all these cases. The degree of hemoglobin increase after administration of recombinant erythropoietin appeared to correlate with the intensity of inhibitory activity of AS. These data indicate the clinical significance of the inhibitor(s) of erythropoiesis in uremic sera and suggest that the clinical effects of erythropoietin in this disease are further improved if the inhibitor(s) can be effectively removed.

Adult↗

Expression of the insulinoma gene rig during liver regeneration and in primary cultured hepatocytes.

We have isolated a novel gene, rig (rat insulinoma gene) from rat insulinomas. In the present study, rig was found to be expressed in rat regenerating liver and in primary cultured rat hepatocytes. The level of rig mRNA was increased at the proliferative phase of liver regeneration. In synchronously cultured hepatocytes, the rig mRNA level was elevated at the G1 phase of the cell cycle and the rig-protein was accumulated in the nuclei during the S phase. These results indicated that rig could be involved in a more general way in growth or cell replication.

Adenoma, Islet Cell↗

Complete nucleotide sequence of human vasoactive intestinal peptide/PHM-27 gene and its inducible promoter.

We have previously shown that the VIP precursor contains a novel PHI-27-like peptide, PHM-27, and that the synthesis of the prepro-VIP/PHM-27 mRNA is induced with cAMP and TPA in human neuroblastoma cells. In this study, we have determined the complete nucleotide sequence of the human VIP/PHM-27 gene. The gene spans 8,837 bp and consists of seven exons and six introns. Exon I of 165 bp consists of the 5' untranslated region of the gene, exon II of 117 bp encodes the signal peptide of prepro-VIP/PHM-27, exon III of 123 bp encodes the amino-terminal region, exon IV of 105 bp encodes PHM-27, exon V of 132 bp encodes VIP, exon VI of 89 bp contains the termination codon of the prepro-VIP/PHM-27 mRNA, and exon VII of 724 bp consists of the 3' untranslated region of the gene. VIP and its structurally related peptide, PHM-27, were encoded in different exons V and IV, and the sequences around the splice junctions between these exons and their adjacent introns were highly conserved, suggesting that the VIP-encoding and PHM-27-encoding exons have been duplicated from an ancestral exon over a broad area containing its adjacent introns. We also determined the 1,929-bp sequence of the 5' flanking region of the human VIP/PHM-27 gene and found that four TATA-box sequences were present at 28 bp, 145 bp, 772 bp, and 900 bp upstream of the cap site. Primer extension, exon mapping, and mung bean nuclease mapping analyses revealed that only the TATA-box sequence 28 bp upstream of the cap site was the promoter that is inducible by cAMP and TPA in the human neuroblastoma cells. An 18-bp sequence 52 bp upstream from the TATA-box sequence was suggested to be a cAMP/phorbol esters-responsive element of the human VIP/PHM-27 gene.

Base Sequence↗

Activated charcoal diminishes the lot difference of fetal bovine sera in erythroid colony formation of human bone marrow cells.

Using normal bone marrow as target cells, we assayed the colony-forming efficiency of early and late erythroid progenitor cells and granulocyte-macrophage progenitor cells using several different lots of fetal bovine serum (FBS). There was a marked difference in the ability of these sera to support colony formation, particularly in erythroid colony assays. When adsorbed by activated charcoal, all these sera supported erythroid colony formation more efficiently than before adsorption. There was no significant effect of charcoal adsorption of FBS on granulocyte-macrophage colony formation. Gel-filtration study showed that charcoal adsorption diminished low-molecular-weight fractions by less than 5000 Da. The inhibitory activity of this fraction was heat labile and Pronase sensitive. Concentrated samples obtained from these fractions inhibited erythroid colony formation in a dose-dependent manner. These results suggest that low-molecular-weight inhibitors that are relatively specific to erythropoiesis play a critical role in the lot differences of FBS for erythroid colony formation.

Adsorption↗

Evolutionary conservation of the insulinoma gene rig and its possible function.

We have identified a gene, rig (rat insulinoma gene), that is activated in chemically induced rat insulinomas but not in normal pancreatic islets or in regenerating islets. In the present study, we have found that the insulinoma gene was activated in a BK virus-induced hamster insulinoma cell line and in a spontaneously occurring human insulinoma. From the hamster and human insulinoma cDNA libraries, rig homologues were isolated, and their nucleotide sequences were determined. In the same manner as the rat gene, both hamster and human homologues contained one open reading frame of 435 nucleotides, differing by 32- and 41-base substitutions, respectively. All the base substitutions were same-sense mutations. Accordingly, the deduced 145-amino acid sequence remained invariant in hamster, human, and rat insulinomas, suggesting that rig has evolved under extraordinarily strong selective constraints. Computerized structure analysis indicated that rig-encoded protein is a possible DNA-binding protein. The antisense oligodeoxyribonucleotide complementary to hamster rig mRNA was synthesized and injected into the hamster insulinoma cells. The antisense rig oligodeoxyribonucleotide inhibited DNA synthesis in the insulinoma cells, whereas the sense rig oligodeoxyribonucleotide or antisense insulin oligodeoxyribonucleotide had no inhibitory effect. These results strongly suggest that the activation of rig is both common and potentially significant in the oncogenic growth of pancreatic B cells of islets of Langerhans.

Adenoma, Islet Cell↗

[Laboratory and clinical studies on cefmenoxime in respiratory tract infections].

Cefmenoxime (CMX, Bestcall) was administered by drip infusion to 65 patients with various respiratory infections and its effect was evaluated. The rate of effectiveness was 86.2% in all cases including 40 cases of acute pneumonia and 12 cases of chronic bronchitis. CMX was examined comparatively with other drugs for antibacterial activity on clinically isolated strains of 2 bacterial species, i.e. H. influenzae and B. catarrhalis, each of which has a high frequency of clinical isolation from infected respiratory organs. On H. influenzae CMX exerted the strongest antibacterial activity among test drugs (ampicillin, piperacillin cefoperazone, latamoxef) regardless of the production of beta-lactamase by the organism, while on B. catarrhalis it also exerted an antibacterial activity strong enough to control the proliferation of all strains at a dose level of 0.39 microgram/ml. Drip infusion of this drug (2 gram) brought about an average maximum blood concentration of 127.2 +/- 21.5 micrograms/ml and an average half-life in blood of 1.10 +/- 0.28 hours. However, different values were obtained for different individual cases because these subjects were patients of chronic respiratory infections each having some underlying disease or other. Side effects of the drug were observed as allergic symptoms such as pyrexia, eruption and the like, but only 5 cases without any serious cases. Increases in transaminase suggestive of abnormal clinical test results were also observed in 5 cases. However, numerical recoveries to the normal values were obtained in all of these 5 cases with the withdrawal of the drug.

Adolescent↗

Effective sites by sympathetic beta-adrenergic and vagal nonadrenergic inhibitory stimulation in constricted airways.

In an attempt to identify the site and nature of nonadrenergic inhibitory nervous regulation in airways, we studied the relative effectiveness of the nervous system in reversing bronchoconstriction along various generations of airways by comparing it with that seen during sympathetic (beta-adrenergic) stimulation in 9 cats. After giving atropine (3 mg/kg), airway dimensions were obtained from roentgenograms after insufflation of powdered tantalum. Baseline bronchoconstriction was then induced by an intravenous infusion of serotonin (50 to 250 micrograms/kg/min). Electrical stimulation of the sympathetic nerves inhibited constriction throughout the airways from trachea down to bronchioli less than 0.5 mm in diameter, with the maximal effect in airways 1 to 4 mm in diameter. The vagi were then stimulated after blocking the adrenergic inhibitory nervous system with propranolol (2 mg/kg). The distribution and potency of the remaining nonadrenergic inhibitory nerve's effect on airway constriction induced by serotonin was comparable to that obtained with sympathetic stimulation. We conclude that the nonadrenergic inhibitory nerves preferentially dilate the midsized airways, which essentially correspond to the sites maximally constricted by vagal stimulation without atropine. The largest (tracheal) and the peripheral airways (less than 1 mm in diameter) are only slightly affected by either inhibitory system.

Animals↗

Effects of elevated temperatures on the embryonic development and corpus luteum activity in the Japanese long-fingered bat, Miniopterus schreibersii fuliginosus.

Gravid female Japanese long-fingered bats were kept in captivity without hibernation at elevated temperatures (23-25 degrees C) in winter. The embryonic growth rate was accelerated and consequently parturition was advanced by a period equivalent to that of exclusion from hibernation as compared with that in the wild population. The corpus luteum became active, as indicated by an increase in the 'light' lutein cells in an experimental bat pregnant with a 15-mm embryo, but was less active (more 'dark' cells) in 2 hibernating control bats with an implanting blastocyst.

Animals↗

Sympathetic and parasympathetic nervous control of airway resistance in dog lungs.

We studied autonomic nervous control of central (Rc), peripheral (Rp), and extremely peripheral (Rep) airway resistances using a combination of a retrograde catheter method and a pleural capsule method. Airflow through the pleural capsule enabled us to measure Rep, which mainly reflected the resistance of local bronchioles less than 0.6 mm in diameter. Rp of the airways less than about 2 mm in diameter was not negligibly small at any lung volume (VL). With vagi intact, Rc increased at high as well as low VL, whereas Rp and Rep increased sharply as VL decreased. Vagal stimulation increased Rp more markedly than Rc, and Rep least of all. Propranolol augmented total airway resistance (Rtot) two to four times as much as vagal stimulation, mainly because of increased Rp. Stimulation of stellate ganglia inhibited up to half the increase of Rtot elicited by vagal stimulation; most of the inhibition occurred in Rp, but little in Rc and Rep. Our data suggest that both sympathetic and parasympathetic control is more extensive for Rp than for Rc or Rep.

Airway Resistance↗

Temperature effects on lung mechanics in air- and liquid-filled rabbit lungs.

Effects of temperature on lung pressure-volume (PV) curves and on the reversibility of changes were studied in the range of 4-52 degrees C. Air curves were obtained first at 21 degrees C, then after 60 min equilibration at one of seven test temperatures (4, 21, 32, 37, 42, 47, and 52 degrees C) and finally again at 21 degrees C. In a given lung, peak inflation volume was made identical at all temperatures. Warming from 4 to 42 degrees C steadily diminished both inflation and deflation pressures, but thereafter the trend reversed except on the upper part of the inflation curve. On returning to 21 degrees C, all PV curves were indistinguishable except from 52 degrees C. Liquid PV curves were obtained in a similar way at four temperatures (4, 21, 37, and 52 degrees C). Warming from 4 to 52 degrees C diminished tissue elastic recoil at total lung capacity (TLC) from 17 to 5 cmH2O but raised recoil slightly at lower lung volumes. Liquid PV curves were also reversible except after 52 degrees C. At 37 degrees C the estimated tissue component of the total recoil of air-filled lungs exceeded 95% at 40-60% TLC, and at 21 degrees was 85-90%. This fraction fell to 50% or less at 4 and 52 degrees C, where surface forces failed to reach low levels and alveolar instability resulted.

Air↗

Temperature and surface forces in excised rabbit lungs.

This study was designed to determine whether the effects of temperature on lung pressure-volume (PV) curves were influenced by the state of the surface lining at the time of warming or cooling. In successive runs, temperature was varied (21, 37, or 5 degrees C) with lung gas volume fixed at either 55% total lung capacity (TLC) or 0% TLC (degassed), followed by PV curves to TLC. Peak inflation volume in a given lung was made identical at all temperatures. The starting pressure at 55% TLC remained fixed during temperature changes, whereas peak pressure ranged from 24 cmH2O at 37 degrees C to 40 cmH2O at 5 degrees C. However, below 75% TLC all deflation curves differed by less than 1 cmH2O, and the lowest recoil occurred at 5 degrees C. At 0% TLC, a similar dispersion in pressures appeared at TLC. However, on deflation, recoil at 37 degrees C was always less than at 21 degrees C, whereas at 5 degrees C a drastic shift to the right occurred. First-cycle hysteresis and midinflation pressure also increased with cooling. Thus, with cooling, the spreading and adsorption of surfactant during lung expansion are inhibited, and during deflation aggregation is greatly facilitated, accounting for the above results. When an already spread surface is cooled, then expanded, as at 55% TLC, the more rigid lining causes some rise in peak pressure at TLC but little change elsewhere. However, when lungs are degassed and then cooled, the aggregated surfactant spreads extremely poorly, leading to greatly increased recoil throughout the cycle. Changes in pressure at TLC may depend considerably on tissue effects.

Animals↗