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Biomedical subjects

T Doi

Publications and source records attributed to T Doi.

At least 163 records · Page 9Linked to original sources

Optical recording of membrane potential on isolated spiral ganglion cells of newborn mice using a voltage-sensitive dye.

Optical imaging methods make monitoring of the membrane potential feasible. With this technique, one can observe different optical signals depending on optical properties, in response to membrane potential, using voltage-sensitive dyes. We used the multiple-site optical imaging system to investigate membrane potentials of the isolated, cultured spiral ganglion cells (SCGs) from newborn mice. We used a voltage-sensitive absorption dye. With high potassium (150 mM K+) exposure, the absorbency of SGCs stained with voltage-sensitive dye increased temporarily under a 700-nm interference filter at approximately 0.3%. This detection of the depolarization of SGCs using an optical recording technique with a voltage-sensitive dye is important because it shows that the simultaneous measurement of activity in a variety of regions is possible, as is the exploring of the intercellular signalling pathway.

Animals↗

An outbreak of hepatitis A in a day-care center: immunoprophylaxis with human immunoglobulin.

BACKGROUND: An outbreak of seven cases of hepatitis A (HA) occurred in a day-care center. Five of the cases were children attending the center, one was a nurse and one was the mother of a child. It is probable that the first case with HA was a male child infected by an unknown source. METHODS AND RESULTS: Human immunoglobulin (HIG) was administered to both children and staff at the center following which there were no new cases of infection among in-center contacts. However, a new case of HA among household contacts developed 3 weeks following the treatment of in-center contacts. CONCLUSIONS: The outbreak may have been prevented if the sibling (case 2) of the source case of infection (case 1) had been given HIG as soon as infection had been confirmed. Additionally, the data suggest that HIG for prevention of HA should be given not only to children but also to their parents.

Adult↗

Therapeutic effect of erythromycin on influenza virus-induced lung injury in mice.

Erythromycin (EM) is an antibiotic with potent antiinflammatory effects that is used for treating chronic lower respiratory tract infections. It has been shown that free radicals, such as the superoxide anion and nitric oxide (NO), are pathogenic molecules in viral disease. Much attention has been given to a critical role of NO in the pathologic events of various inflammatory diseases. In the present study, we evaluated the effects of EM on influenza-virus-induced pneumonia in mice infected with a lethal dose of influenza virus A/Kumamoto/Y5/67 (H2N2). The administration of EM at a dose of 3.3 mg/kg/d (intraperitoneally, from Days 1 to 6 after infection), significantly improved the survival rate of mice infected with influenza virus, and the survival rate of the virus-infected mice at Day 20 after infection increased in a dose-dependent fashion with EM administered to the animals, from 14% among controls to 42% among animals given EM at 1.0 mg/kg/d and 57% among those given EM at 3.3 mg/kg/d. The induction of interferon-gamma (IFN-gamma) in the mouse lung was inhibited by EM treatment on Day 6 after infection. Simultaneously, the number of inflammatory cells recovered in lung lavage fluid 6 d after virus infection was significantly reduced by the treatment with EM. The EM treatment resulted in a dose-dependent decrease in the level of nitrite/nitrate (metabolites of NO) in the serum and the NO synthase (NOS)-inducting potential in the lungs of the virus-infected mice. These results indicate that EM may have substantial therapeutic value for various acute inflammatory disorders such as influenza-virus-induced pneumonia, by inhibiting inflammatory-cell responses and suppressing NO overproduction in the lung.

Animals↗

Anti-inflammatory, analgesic and anti-pyretic effects of d-2-[4-(3-methyl-2-thienyl)phenyl]propionic acid (M-5011), a new non-steroidal anti-inflammatory drug, in rats and guinea pigs.

Anti-inflammatory, analgesic and anti-pyretic effects of d-2-[4-(3-methyl-2-thienyl)phenyl]propionic acid (M-5011), a new non-steroidal anti-inflammatory drug (NSAID), were compared with those of indomethacin, diclofenac sodium and ketoprofen in rats and guinea pigs. Anti-inflammatory effect of M-5011 on ultraviolet-induced erythema in guinea pigs was 11.7 and 1.8 times more potent than that of indomethacin and ketoprofen, respectively. Inhibitory effect of M-5011 on carrageenin-induced paw edema was 2 and 1.5 times more potent than that of indomethacin and diclofenac sodium, respectively. Analgesic effect of M-5011 on dry yeast-induced hyperalgesia or adjuvant-induced arthritic pain was equipotent to that of indomethacin, diclofenac sodium or ketoprofen. Anti-pyretic effect of M-5011 on yeast-induced pyrexia in rats was 4.2 and 4.6 times more potent than that of indomethacin and ketoprofen, respectively. Inhibitory effect of M-5011 on prostaglandin E2 production in the exudate of air-pouch inflammation induced by carrageenin was 1.75 times more potent than that in the non-inflamed site (stomach). As a result, gastric ulcerogenic activity of M-5011 was half that of indomethacin in rat. These results suggest that M-5011 shows more potent anti-inflammatory and anti-pyretic effects and equipotent analgesic effect with low gastro-ulcerogenic activity compared with classical NSAIDs.

Analgesics, Non-Narcotic↗

[Acute myocardial infarction due to traumatic hemorrhagic shock with open fracture: a case report of staged amputation and CABG].

A 55-years-old man was admitted to an emergent hospital with hypovolemic pre-shock and open fracture of the right lower extremity. CPR was needed for myocardial infarction induced by hemorrhagic shock. Wound infection and bacteremia (Enterococcus SP) were noted 10 days after admission. Severe three vessel disease was demonstrated by preoperative (amputation) evaluation, he was also referred for CABG. For a control of infectious focus before using cardiopulmonary bypass, two-stage-operation (amputation and CABG) were selected. Both perioperative courses were uneventful and the patient recovered well after rehabilitation.

Amputation, Surgical↗

Demonstration of DNA replication factor C in human glomerular lesions.

Glomerulosclerosis is a common pathological finding in many human glomerular diseases that ultimately leads to end-stage kidney disease. The regulatory mechanism that controls mesangial proliferation as well as accumulation of mesangial matrix, however, is not known. Recently, a protein factor (MSW) which binds to the specific sequence of the promoter of the alpha 1 and alpha 2 type IV collagen genes was cloned. MSW was found to be identical to a large subunit (Alp145) of DNA replication factor C. These findings suggest that MSW may have important functions in mesangial cell proliferation and type IV collagen synthesis, both of which are prominent findings in glomerulosclerosis. In the present study, we report that augmented expression of MSW protein in human glomerular diseases that exhibit glomerulosclerosis (IgA nephropathy, membranoproliferative glomerulonephritis, and focal glomerulosclerosis). Minimal expression of MSW protein was observed in human glomerular diseases that rarely show glomerulosclerosis (membranous nephropathy, and minimal change nephrotic syndrome). There was a significant correlation between the levels of MSW expression and type IV collagen expression. Elevated expressions of both proliferating cell nuclear antigen and MSW were also observed in most patients with proliferative glomerular diseases. These studies suggest that MSW protein plays a regulatory role in the development of mesangial cell proliferation and matrix expansion during progression of glomerular injuries.

Adult↗

[Improvement of cognition after trepanation for the chronic subdural hematoma].

The cognitive functions were examined in the pre- and post-operative stages about the 16 cases of the chronic subdural hematoma. The evaluation was performed with MMS (mini-mental state) test. Although the average of the total score was 16.6 in the preoperative stage, it increased to 22.7 in the postoperative stage. Orientation of time and place, recall and the ability of writing a sentence, which were impaired prominently in the preoperative stage, improved significantly in the postoperative stage. The improvement was poorer in the patients with gait instability and in those older than 80 years. Trepanation surgery seems to be efficient for the improvement of cognition.

Aged↗

[Clarification of Amae as a concept--response to the criticism by K. Nagayama].

Nagayama wrote a lengthy paper in order to demonstrate that the amae theory which I propounded is all confused. I should say on the contrary that the confusion is his own because he dose not realize that he and I may mean different things by the same word amae. Apparently he means those phenomena that indicate the fulfilment of amae, while I take amae as a verbnoun of amaeru meaning the operation of amaeru in one way or another irrespective of the outcome, its prototype being that of an infant seeking its mother. In short, for Nagayama amae is a characteristic of certain Japanese phenomena and for me a concept. It may refer, in psychoanalytic thinking, to that primordial urge for object relations. It makes no sense therefore to censure my wording of amae like 'narcissistic amae' as not measuring up to the true state of amae as Nagayama defines it, because my usage of the word amae is entirely different from his. In this connection I may point out a curious resemblance between the dismissive manner of his criticism and the behavior of a small group embodying amae which he characterizes as distinctly exclusive of outsiders. There is a good reason to believe that the resemblance is not accidental. I must say that Nagayama is most confused in his critical appraisal of the amae theory against Balint's theory. He completely ignores the fact that these two theories developed independently though there is a definite parallel between them. He then takes me to task that I did not properly incorporate Balint's late ideas into my thinking, even though those ideas became known only in the books published after that book of mine which is the butt of his criticism. Nagayama attempts to trace the amae phenomena back to some racial unconscious underlying Japanese culture. He may believe so, but it sharply contrasts with my view that the very availability of such a concept like amae is indicative of the tenor of Japanese culture. It is interesting to note here that all critics of the amae theory including Nagayama stumble on amae as a concept. They just cannot imagine that one can fetch a Japanese word and make it a universal concept. It must be their unspoken belief that all the valid concepts in whatever field of study come from abroad, notably the West.

Cultural Characteristics↗

Antisense oligonucleotides against collagen-binding stress protein HSP47 suppress collagen accumulation in experimental glomerulonephritis.

Heat shock protein 47 (HSP47) is a collagen-specific molecular chaperone that has been shown to play a major role during the biosynthesis and secretion of procollagen molecules. The expression of HSP47 has been reported to increase in parallel with the expression of collagens during the progression of various fibrosis models. However, it remains unclear whether an inhibition of HSP47 overexpression would suppress collagen accumulation and thus reduce the progression of fibrotic diseases. In this study, we attempted to attenuate glomerular collagen accumulation by inhibiting the overexpression of HSP47 with antisense oligodeoxynucleotides in an experimental glomerulonephritis model induced by anti-Thy-1 antibodies. The administration of antisense oligodeoxynucleotides against HSP47 at the induction of the glomerular disease markedly suppressed the increased production of collagens and attenuated the histologic manifestations of the disease. These results provide direct evidence of a pivotal role for HSP47 in the pathogenesis of glomerulonephritis.

Animals↗

Spiroxys hanzaki n. sp. (Nematoda: Gnathostomatidae) collected from the giant salamander, Andrias japonicus (Caudata: Cryptobranchidae), in Japan.

Spiroxys hanzaki n. sp. (Nematoda: Gnathostomatidae) taken from the giant salamander, Andrias japonicus (Temminck, 1836) (Caudata: Cryptobranchidae) from Hyogo Prefecture, Japan, is described. It closely resembles Spiroxys allegheniensis Walton, 1930, from the hellbender, Cryptobranchus alleganiensis (Daudin, 1803) (Cryptobranchidae), of North America, in that it has minute dorsal and ventral lobes of the pseudolabium and a reduced gubernaculum but is readily distinguished by a pseudolabium with 2 apical, 1 dorsal, and 1 ventral tooth on the median lobe.

Animals↗

[Fleroxacin treatment for acute uncomplicated cystitis in women: comparison of 3-day and 7-day therapy].

The clinical efficacy of fleroxacin (FLRX), a new fluoroquinolone, for acute uncomplicated cystitis (AUC) in women was assessed. Two regimens, 3-day and 7-day courses of FLRX, 200 mg once a day, were compared. Clinical and bacteriological efficacy were evaluated after the therapy, and recurrence rate was evaluated 1 week and 4 weeks after termination of the therapy. Of 136 registered subjects, 35 in the 3-day group and 47 in the 7-day group were evaluated. According to the criteria of Japanese UTI Committee (3rd edition), the rate of excellent results was significantly higher in the 7-day group (78.9%) than in the 3-day group (48.6%), but the overall clinical efficacy rate was similar being 100% and 97.9%, respectively. Although no recurrence was seen 1 week after the therapy in either group, recurrence was seen in 14.3% and 7.4% of the cases in the 3-day and 7-day groups, respectively, 4 weeks after the therapy. Adverse reactions were observed in 2 and 3 cases in the 3-day and 7-day groups, respectively. Both 3-day and 7-day regimens of FLRX treatment showed good efficacy. Although the 7-day treatment was superior to the 3-day treatment as to high rate of excellent results and low rate of recurrence, the 3-day treatment was concluded to be sufficient for AUC.

Adult↗

[Simultaneous cholecystectomy and CABG for acute cholecystitis and post-infarction angina].

A 71-year-old man was admitted to our hospital with massive GI bleeding and followed by acute myocardial infarction. Severe three vessel coronary artery disease with poor left ventricular performance (EF: 40%) was demonstrated by coronary angiography. He was referred for CABG. He had also cholecystitis, which needed surgical treatment simultaneously. Combined CABG and cholecystectomy were performed without using gastroepiploic artery as a bypass graft, and through separate median sternotomy and through right upper transrectal laparotomy. Postoperative course was uneventful. This combined procedure is beneficial for the patients with acute cholecystitis and unstable angina.

Acute Disease↗

The conformation of the alpha-helical coiled coil domain of macrophage scavenger receptor is pH dependent.

Macrophage scavenger receptor is a trimerized membrane protein that binds ligands and undergoes internalization by endocytosis. The receptor releases the ligands in the endosome, and then is recycled. The mechanisms of the ligand release and the recycling of the receptor have not been clearly determined. We analyzed the structure of the alpha-helical coiled coil domain considered to be responsible for acid-mediated ligand dissociation, by chemical cross-linking, sedimentation equilibrium, Western blot, and circular dichroism analyses. This domain has 22 heptad repeats, which are characteristic of the sequence of an alpha-helical coiled coil structure, with a discontinuity in the middle. We prepared three peptides, corresponding to the entire alpha-helical coiled coil domain (alpha), its N-terminal half (alpha-N), and its C-terminal half (alpha-C), by expression of each gene in Escherichia coli. The alpha and alpha-N peptides show triple-stranded alpha-helical coiled coil structures, but in contrast, the alpha-C peptide shows a random structure. When connected to the N-terminus by a chemical ligation method, the alpha-C peptide also shows an alpha-helical coiled coil structure, but only at an acidic pH. These results suggest that the N-terminus of the alpha-helical coiled coil domain is responsible for the formation of a stable trimer and the C-terminus exhibits the pH-dependent conformational change that might be involved in the ligand release by the macrophage scavenger receptor.

Amino Acid Sequence↗

The lysine cluster in the collagen-like domain of the scavenger receptor provides for its ligand binding and ligand specificity.

Scavenger receptors bind modified low-density lipoproteins (LDL) on a collagen-like domain which possesses a lysine cluster at the carboxy end. We previously constructed a receptor model peptide containing the lysine cluster. In the present study, we evaluated the ligand specificity of the receptor model peptide. It selectively bound modified-LDLs, and not LDL. The binding of acetylated-LDL (Ac-LDL) was inhibited by dextran sulfate, fucoidan, and sulfatides in a manner similar to that of the natural receptor. Both polyguanylic and polyinosinic acids inhibit the Ac-LDL binding whereas polycytidylic acid did not. These results indicate that the lysine cluster in the collagen-like domain has important roles in both ligand binding and ligand specificity.

Amino Acid Sequence↗

Characterization of human endothelin B receptor and mutant receptors expressed in insect cells.

Endothelin type-B receptor (ET(B)R) forms a stable complex with its ligand, endothelin-1. To facilitate biochemical and biophysical studies of human ET(B)R, several ET(B)R mutants carrying a hexahistidine tag sequence at the N or C terminus were expressed in Sf9 cells and were purified by a combination of biotinylated endothelin-1-ligand-affinity and nickel-affinity chromatographies. The ligand-free receptor was purified by dissociating the ligand x receptor complex with 2 M NaSCN, whereas the ligand-bound ET(B)R was purified by the use of thiol-sensitive biotinylated endothelin-1. While the wild-type ET(B)R was expressed at about 100 pmol 125I-endothelin-1-binding activity/mg membrane protein, the deletion of 36 residues from the N-terminus reduced the expressed activity to about 30%. On the other hand, the lack of glycosylation and the replacement of 2-9 residues in the N-terminal tail resulted in a 20-40% reduction in the expressed activity. Among the mutant proteins, [H57-H62, G63-G65]ET(B)R, carrying six His residues in the N-terminal tail, was studied extensively because it was purified most effectively. Ligand-free [H57-H62, G63-G65]ET(B)R, purified in digitonin, retained full ligand-binding activity, while other detergents led to partial denaturation of the receptor after solubilization or after elution with NaSCN. On the other hand, ligand-bound [H57-H62, G63-G65]ET(B)R could be purified in various detergents, such as n-octyl-beta-D-glucopyranoside or n-decyl-beta-D-maltopyranoside. Ligand-free [H57-H62, G63-G65]ET(B)R reconstituted in phospholipid vesicles stimulated the binding of guanosine 5'-3-O-(thio)triphosphate by Gq in the presence of endothelin-1. Ligand-bound [H57-H62, G63-G65]ET(B)R showed similar catalytic activity in nucleotide exchange by Gq. These results indicate that the ligand x receptor complex in a detergent-micellar solution retained the biologically active structure, and that the presence of ligand, endothelin-1, in the receptor molecule reinforces the stable assembly of a helical bundle and therefore the active structure.

Amino Acid Sequence↗