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Biomedical subjects

S Kikuchi

Publications and source records attributed to S Kikuchi.

At least 343 records · Page 19Linked to original sources

Inhibitory action of tranilast, an anti-allergic drug, on the release of cytokines and PGE2 from human monocytes-macrophages.

Tranilast, an anti-allergic drug that inhibits the release of substances such as histamine and prostaglandins from mast cells, has been reported to improve keloids and hypertrophic scars which originate from the abnormal proliferation and excessive collagen accumulation of fibroblasts. It has been considered that various chemical mediators produced by inflammatory cells play important roles in the development of keloids and hypertrophic scars. We therefore studied the effect of tranilast on the release of chemical mediators including transforming growth factor (TGF)-beta 1, interleukin (IL)-1 beta and prostaglandin (PG) E2 which are produced by the human monocytes-macrophages, and estimated whether these mediators induce collagen synthesis and cell proliferation of normal skin fibroblasts. Tranilast inhibited the release of TGF-beta 1, IL-1 beta and PGE2 from the human monocytes-macrophages. TGF-beta 1 (25-200 pM) enhanced the collagen synthesis by fibroblasts. IL-1 (0.1-1 U/ml) increased the proliferation and conversely decreased the collagen synthesis. PGE2 (2 micrograms/ml) enhanced the collagen synthesis. These results suggest that tranilast suppresses collagen synthesis by fibroblasts through inhibiting TGF-beta 1 and PGE2 production and cell proliferation by fibroblasts through inhibiting IL-1 production by inflammatory cells such as macrophages.

Adult↗

The mechanism involved in the inhibitory action of tranilast on collagen biosynthesis of keloid fibroblasts.

Tranilast, an anti-allergic drug inhibiting the release of substances such as histamine and prostaglandins from mast cells, was previously reported to suppress collagen synthesis of fibroblasts derived from keloid tissues. However, the inhibitory mechanism on collagen synthesis is unknown. We studied its inhibitory mechanism on collagen synthesis by culturing fibroblasts from keloid and hypertrophic scar tissues of humans. Collagen synthesis of fibroblasts from keloid and hypertrophic scar tissue is greater than that from healthy human skin. Tranilast (3-100 microM) did not inhibit prolyl hydroxylase (the rate-limiting enzyme in collagen synthesis) activity. Tranilast (3-300 microM) suppressed the collagen synthesis of fibroblasts from keloid and hypertrophic scar tissue but not healthy skin fibroblasts. Tranilast (30-300 microM) inhibited the release of transforming growth factor (TGF)-beta 1 from keloid fibroblasts, which enhances the collagen synthesis of keloid fibroblasts. Anti-TGF-beta 1 antibody (50 microliter/ml) inhibited the collagen synthesis, although diphenhydramine (10 microM) and indomethacin (10 microM) did not show any inhibition. These results suggest that tranilast inhibits collagen synthesis of fibroblasts from keloid and hypertrophic scar tissue through suppressing the release of TGF-beta 1 from the fibroblasts themselves.

Cicatrix↗

Molecular cloning and characterization of gravity specific cDNA in rice (Oryza sativa L.) suspension callus.

Rice (Oryza sativa L. var. Nipponbare) suspension callus was exposed to gravity stress at 450,000 g for 2 hours, after which poly(A)+RNA was isolated and a cDNA library was constructed. Three different gravity specific cDNAs, namely, GSC 128, GSC 233 and GSC 381 of 0.67, 0.60 and 0.68 kilobase pairs and transcripts of 1.9, 1.6 and 2.0 kb, respectively, were isolated by differential screening and Northern hybridization. The maximum level of transcript was achieved after 4 hours of exposure to gravity at 450,000 g for GSC 128, 2 hours for GSC 233 and 8 hours for GSC 381 followed by a gradual decrease to undetectable levels with the extension of gravitation time. Callus (GSC 128), shoot and callus (GSC 381) and root and callus (GSC 233) specific expression of transcripts was identified. Although the protection of callus by treatment with ABA, kinetin and sucrose extended the period of expression of mRNA in suspension callus after gravity exposure, the expression of gravity-inducible mRNA was exclusively regulated by the degree of callus viability or survival after the stress. In addition, we demonstrated that the level of GSC 381 transcript was markedly increased by exposing the cell to periodical gravity stress, suggesting that this mRNA is expressed and translated into special proteins which are closely related to the survival of the cell against gravity stress. The sequence of GSC 233 and GSC 381, consisting of 417 and 531 base pairs of the longest open reading frames, encode polypeptides with calculated molecular weights of 15.29 and 19.47 kDa, respectively. A sequence homology search against a data bank revealed that GSC 233 and GSC 381 differed from other stress inducible genes in terms of the coding sequence and expression characteristics.

Adaptation, Physiological↗

[Prognosis of acute low-tone sensorineural hearing loss].

We studied 50 patients with acute low-tone sensorineural hearing loss (ALHL) who were examined at the Department of Otolaryngology, University of Tokyo, and followed up for 18 months or more. We investigated the prognosis of hearing loss within 3 months after onset, rate of recurrence during long-term follow-up, interval between the first and the second episodes of hearing loss or between onset and the time when the diagnosis of Meniere's disease was made, and factors affecting prognosis. The results were as follows. 1. Within the initial 3 months of follow-up, hearing loss continued to fluctuate in 5 patients. In the remaining 45, hearing returned to normal in 34, improved without returning to normal in 6, showed no marked change in 4, and became worse in one. 2. In long-term follow-up, the recurrence of hearing loss without vertigo occurred in 16 patients, and 5 others were eventually diagnosed as having Meniere's disease. The average interval between the first and second episodes of hearing loss was 9.2 months, and the diagnosis of Meniere's disease was made an average of 27 months after onset. 3. Recurrence was not significantly related to the initial prognosis of hearing loss. 4. Within the initial 3 months of follow-up, the prognosis of hearing loss was significantly better in patients whose hearing loss at 1 kHz was within 20 dB, and tended to be better in females and in patients attending within one week of onset. Long-term follow-up showed that the rate of recurrence was significantly lower in patients aged 40 years or more, and tended to be lower in patients who visited the hospital within one week of onset or whose hearing loss at 1 kHz was within 20 dB. 5. There were no significant differences between patients with single and recurrent attacks with respect to sex, subjective symptoms, and results of the glycerol test and electrocochleography. ALHL tends to recur without any relationship to the initial prognosis of hearing loss. Since it is still difficult to predict whether or not hearing loss will recur, long-term follow-up is necessary even in patients with good initial prognosis.

Acute Disease↗

[Quantitative analysis of cholesteatoma using high resolution computed tomography].

Seventy-three cases of adult cholesteatoma, including 52 cases with pars flaccida type cholesteatoma and 21 with pars tensa type cholesteatoma, were examined using high resolution computed tomography, in both axial (lateral semicircular canal plane) and coronal sections (cochlear, vestibular and antral plane). These cases were classified into two subtypes according with the presence of extension of cholesteatoma into the antrum. Sixty cases with chronic otitis media with central perforation (COM) were also examined as controls. The various locations of the middle ear cavity were measured in term of size with comparisons among pars flaccida type cholesteatoma, pars tensa type cholesteatoma and COM. The results were as follows: 1) The width of the attic was significantly larger in both pars flaccida type and pars tensa type cholesteatoma than in COM. 2) With pars flaccida type cholesteatoma there was a significantly larger distance between the malleus and lateral wall of the attic than with COM. In contrast, the distance between the malleus and medial wall of the attic was significantly larger with pars tensa type cholesteatoma than with COM. 3) With cholesteatoma extending into the antrum, regardless of the type of cholesteatoma, there were significantly larger distances than with COM at the following sites; the width and height of the aditus ad antrum, and the width, height and anterior-posterior diameter of the antrum. However, these distances were not significantly different between cholesteatoma without extension into the antrum and COM. The hitherto demonstrated qualitative impressions of bone destruction in cholesteatoma were quantitatively verified in detail using high resolution computed tomography.

Adolescent↗

[Time course of drug concentrations in nebulizers and nebulized solutions].

The drug concentrations in nebulizers and nebulized solutions generated by the ultrasonic nebulizer OMRON NE-U10B and the jet nebulizer INSPIRON NEBULIZER 002305 were examined. With the ultrasonic nebulizer, increases in the concentrations of saline, DSCG and isoproterenol in the nebulizer were observed; the concentrations of those in the nebulized solutions also increased. The increase was most dramatic just before the solution was emptied. No degradations of DSCG or isoproterenol were detected in the nebulized solutions, indicating that these drugs are stable against ultrasonic nebulization. An increase in the drug concentrations in the jet nebulizer was also observed. The concentrations of the nebulized solutions also increased, but the concentrations in the nebulized solution were lower than those in the nebulizer at any time. On inhalation therapy, it is important to give consideration to these concentration changes. The nebulizer should not, for example, be refilled with a new drug solution.

Cromolyn Sodium↗

[Correlation between clinical features and neuroradiological findings in juvenile muscular atrophy of unilateral upper extremity (Hirayama disease)--with and without "tight dural canal in flexion"].

Myelography was performed in 12 patients with juvenile muscular atrophy of unilateral upper extremity. Seven patients showed anterior shift of lower cervical dural canal in flexion (tight dural canal in flexion) (T group), however the other 5 patients did not show "tight dural canal in flexion" (NT group). Onset of illness and sex were not different between 2 groups. However, there was a tendency that the neurological signs and symptoms were more severe in the patients of T group than those of NT group. These results suggest that "right dural canal in flexion" can be one of mechanisms which exhibit the clinical symptoms of the juvenile muscular atrophy of unilateral upper extremity. However, there may be other etiological factors in the juvenile muscular atrophy of unilateral upper extremity.

Adolescent↗

[A case of chondrosarcoma originating from the left third rib].

Chondrosarcoma of rib origin is rare in Japan. A 51-year-old man came to our hospital with chest pain and coin lesion in the left superior part of the chest X-ray film. It was suspected to be the posterior mediastinal tumor based on CT and MRI. Operation was done to remove the tumor and the histological diagnosis was chondrosarcoma. The tumor measured 2.5 x 2.6 x 2.2 cm arising from the posterior portion of the left third rib. Combined resection of descending aortic adventitia was done. The patient is doing well without symptoms of recurrence 15 months after operation.

Aorta, Thoracic↗

[Problems associated with mass-screening system for gastric cancer in Japan].

In the mass-screening system for gastric cancer, subjects are primarily examined by contrasted indirect roentgenography and if secondary examination is diagnosed to be necessary, they are examined by contrasted direct roentgenography or gastric fiberscopy. Methods for increasing the efficiency of this system from the standpoint of cost-effectiveness were studied, and the basis for decision of whether or not serological examinations such as of serum pepsinogens and serum anti-Helicobacter-antibodies should be brought in to the system, and in what manner serological examinations should be brought in to the system if proven to be effective were examined. Problems found in the present practiced system and the proposed new system with serological examinations were repetition interval for examinations, selection of high-risk subjects and communication between subjects and the medical staff or among the members of the medical staff. Analysis by receiver operating characteristics curve should be included when serological examinations are indicated. In addition whether the mass-screening system for gastric cancer produces an actual reduction in death by gastric cancer should be confirmed after the system is made more efficient.

Female↗

Serodiagnosis of hepatitis C virus (HCV) infection with an HCV core protein molecularly expressed by a recombinant baculovirus.

An enzyme-linked immunosorbent assay (ELISA) was developed for serological diagnosis of hepatitis C virus (HCV) infection, using HCV core protein (p22) synthesized by a recombinant baculovirus. Among 58 clinically well-defined chronic non-A, non-B hepatitis (NANBH) patients, 49 (84.5%) were positive for p22 antibody (anti-p22), whereas 42 (72.4%) were positive for C100-3 antibody (anti-C100-3), as measured by the present assay using the HCV nonstructural protein as antigen. Thirty-nine patients (67.2%) had both antibodies. No significant level of anti-p22 was detected in sera of chronic hepatitis B patients or normal blood donors. In typical post-transfusion NANBH patients, anti-p22 could be detected at, or even before, the first alanine aminotransferase peak. Anti-p22 was also detected in blood donors who were previously shown to be involved in transmitting HCV but in whose serum anti-C100-3 was not detectable. The ELISA detecting antibody to the HCV core protein expressed and properly processed in animal cells will be useful for mass screening of donor blood as well as for early diagnosis of hepatitis C.

Animals↗

Stopped-flow investigation of the reaction of vitamin C with tocopheroxyl radical in aqueous triton X-100 micellar solutions. The structure-activity relationship of the regeneration reaction of tocopherol by vitamin C.

A kinetic study of the reaction between vitamin C (L-ascorbic acid, AsH2) and a tocopheroxyl radical (7-tert-butyl-5-isopropyltocopheroxyl) in Triton X-100 micellar solution has been performed using stopped-flow spectrophotometry. The second-order rate constants (k2) obtained showed notable pH dependence with a broad maximum around pH 8. For instance, the k2 values obtained were 26 M-1 S-1 at pH 3, 322 M-1 S-1 at pH 7, and 273 M-1 S-1 at pH 10. A good correlation between the rate constants and the mole fraction of ascorbate monoanion (AsH-) was observed, showing that ascorbate (AsH-) can regenerate the tocopherol from tocopheroxyl in biological systems. Furthermore, the results indicate that reduced ascorbic acid (AsH2) does not have the ability to regenerate the tocopherol in aqueous solution. On the other hand, it was found that AsH2 can reduce the tocopheroxyl to tocopherol in benzene/ethanol (2:1) mixtures, although the rate of reaction is only approximately 15% of that observed in micellar solution at pH 7.

Ascorbic Acid↗

Identification and structural characterization of further DNA elements in the potato and pepper genomes homologous to the transposable element-like insertion Tst1.

The molecular cloning and nucleotide sequence of elements from potato and pepper that are related to the recently identified Tst1 element are described. Sequence analysis reveals considerable conservation of sequences internal to both the Tst1 element and two of the related elements identified here. In six potato clones analysed, the 11 bp inverted repeat first identified in the Tst1 element is conserved. Several of the elements are flanked by an 8 bp direct repeat. DNA fragments which were amplified from several pepper genomes by polymerase chain reaction (PCR) amplification using the inverted repeat as sequence primers also display considerable conservation of sequences internal to the Tst1 element. These data further support the possibility that Tst1 is a non-autonomous transposable element and that Tst1 might be the first example of a transposable element which occurs in several genera of solanaceous plants.

Base Sequence↗

Collagen gel contraction by fibroblasts requires cellular fibronectin but not plasma fibronectin.

Fibroblasts embedded in three-dimensional lattices of collagen fibrils have been known to require serum constituents to induce a cell-mediated contraction of collagen gels. The gel contraction was studied with human skin fibroblasts cultured in the presence of fetal bovine serum (FBS). Removal of bovine serum fibronectin (sFN) from FBS did not affect the extent of gel contraction. Gel contraction occurred in serum-free defined media. Therefore, it is concluded that sFN is not required for gel contraction. That cellular FN (cFN) synthesized and secreted by fibroblasts plays a crucial role in gel contraction was suggested by the following experiments: (1) We obtained monoclonal antibodies (mAb A3A5) against fibroblast surface antigens, which suppressed the fibroblast-mediated gel contraction. Immunoblot analyses showed that mAb A3A5 recognizes cFN secreted by human fibroblasts and human plasma FN (pFN), but not bovine sFN in FBS used for culture. (2) Addition of rabbit antisera, which recognize human cFN, to a serum-free gel culture inhibited contraction. Uninvolvement of human pFN in gel contraction was further confirmed by the fact that neither pretreatment of fibroblasts with excess amounts of human pFN nor the presence of excess amounts of human pFN in gels affected the extent of gel contraction. This study seems to be the first demonstration of functional difference between cFN and pFN (or sFN) and proposes a novel mode of binding of fibroblasts with collagen fibrils via cFN during cell-mediated collagen morphogenesis.

Antibodies, Monoclonal↗

Chai-ling-tang (Japanese name: sairei-to) as an oral adjuvant.

Immunomodulating and anti-tumor activities of orally administered Chai-Ling-Tang (Japanese name: sairei-to, ST) were investigated. The oral administration of ST into mice augmented the antibody response to intraperitoneally administered 2, 4, 6-trinitrophenyl-haptenated sheep red blood cells (TNP-SRBC). Orally administered ST showed also an enhancing effect on the antibody response to TNP-SRBC administered by the oral route. In addition, orally administered ST markedly activated the peritoneal macrophages to enhanced phagocytic and lysosomal enzyme activities. A significant inhibition of tumor growth was observed in a syngeneic tumor-mouse system when ST was administered orally. These results suggest that ST has an efficiency as an oral adjuvant or an oral biological response modifier (BRM).

Adjuvants, Immunologic↗

Kindling-induced changes of [3H]GTP binding in the cerebral cortical membrane.

Specific [3H]GTP binding to the cerebral cortical membrane was examined in amygdaloid kindled rats. Membrane fractions of the cerebral cortex obtained from kindled rats and sham operated control were incubated with [3H]GTP and the data were analyzed by Scatchard plots. There were no differences in the Bmax and Kd values in basal (without any agonists) binding between kindled and control membranes. In the presence of isoprenaline, beta-agonist, Bmax values increased in the control, but did not increase in the kindled group. The kindling-induced abolishment of isoprenaline effect on Bmax of GTP binding persisted at least two weeks. Specific GTP binding activity of control membrane increased in the presence of carbachol, muscarinic agonist. A carbachol-induced increase in specific GTP binding activity also disappeared in the kindled group. These results suggest that a functional imbalance among various types of GTP binding proteins (Gs, Gi or Go) might be related to the acquisition of the epileptogenesis in the kindling model of epilepsy.

Amygdala↗

Effects of dextran sulphate on renal dysfunctions induced by gentamicin as determined by the kidney perfusion technique in rats.

The effect of dextran sulphate on accumulation of gentamicin within the renal cortex and on renal functional changes induced by gentamicin has been investigated using the rat renal perfusion technique. Gentamicin accumulation decreased by the coadministration of dextran sulphate, the degree being proportional to dextran sulphate concentration. The filtered load of gentamicin was unaffected by dextran sulphate. The perfusion of kidney with gentamicin brought about a decrease in the reabsorption of Na+ and an increase in the rate of urine flow with no effect on that of glomerular filtration. The addition of dextran sulphate in the perfusate resulted in the resumption of these levels to those of the control. Dextran sulphate thus apparently interacts with gentamicin in the lumen of proximal tubules to inhibit the reabsorption of gentamicin by proximal tubular cells, and prevents the renal dysfunctions induced by gentamicin.

Animals↗