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Biomedical subjects

S Kikuchi

Publications and source records attributed to S Kikuchi.

At least 19 recordsLinked to original sources
PubMed1992

Leukemia inhibitory factor (LIF) mediated increase of choline acetyltransferase activity in mouse spinal cord neurons in culture.

The effects of leukemia inhibitory factor (LIF) on choline acetyltransferase (ChAT) enzyme activity in cultured mouse spinal cord neurons were examined. The administration of LIF to cultures at concentrations of 10 U/ml and higher enhanced ChAT activity approximately 3- to 4-fold in cultured spinal cord neurons. Among neurotrophic factors tested, basic fibroblast growth factor (bFGF) and insulin-like growth factor I (IGF-I) stimulated the development of ChAT activity but to a smaller extent than LIF, while interleukin 3 (IL-3), interleukin 6 (IL-6) and nerve growth factor (NGF) showed no apparent effect on ChAT development. Our results indicate that LIF, which has not been known to have any trophic effect on mammalian central nervous system neurons to date, acts as a potent differentiation factor for ChAT in cholinergic neurons of mouse spinal cord in culture.

Animals↗
PubMed1992

Study of low molecular weight heparin effect on the relation between anticoagulant activity and antithrombin III affinity.

Low molecular weight heparin (FR-860), and conventional unfractionated heparin (UF-heparin) were fractionated by rabbit antithrombin III (AT III)-Sepharose, and the effects of each affinity fraction on the coagulation and fibrinolytic activities were investigated. FR-860 was fractionated to no-affinity, low-affinity (LA) and high-affinity (HA) fractions, and UF-heparin to LA and HA fractions. The HA fractions showed higher activities regarding the prolongation of activated partial thromboplastin time, anti-factor Xa activity and antithrombin activity compared with those of LA. The HA and LA fractions exhibited the enhancement of heparin cofactor II (HC II) activity and fibrinolytic activity in a dose-dependent manner. These results suggest that the antithrombotic activity of FR-860 is exerted through AT III and other mechanism such as HC II-mediated system.

Animals↗
PubMed1992

Recombinant human erythropoietin for autologous blood donation: effects on perioperative red-blood-cell and serum erythropoietin production.

To speed collection of blood for autologous transfusion during elective surgery, patients may be given recombinant human erythropoietin (r-HuEPO). In a controlled trial, we evaluated the effects of r-HuEPO on perioperative red-blood-cell and serum erythropoietin (s-EPO) production in patients donating blood before elective orthopaedic surgery. Patients were assigned randomly to receive no r-HuEPO (12 patients), or 3000 U (4), 6000 U (5), or 9000 U (4) of r-HuEPO intravenously twice a week from the time of the first blood donation. All patients received iron sulphate. 1200 ml blood was collected from each patient in three weekly donations of 400 ml. The 3000, 6000, and 9000 U treatment groups produced 284, 350, and 383 ml, respectively, of red cells during donation, and the untreated controls produced 211 ml. s-EPO concentrations were within the normal range during donation. After surgery, s-EPO concentrations peaked on postoperative day 1 in untreated patients and on day 7 in treated patients; therefore, r-HuEPO may suppress endogenous erythropoietin secretion. Although administration of r-HuEPO increases production of red blood cells, the preoperative anaemia induced by repeated phlebotomy without r-HuEPO may accelerate the postoperative secretion of endogenous erythropoietin.

Adolescent↗
PubMed1992

Improved serodiagnosis of non-A, non-B hepatitis by an assay detecting antibody to hepatitis C virus core antigen.

We examined sequential serum samples from 12 patients with well-characterized posttransfusion non-A, non-B hepatitis who had an acute, resolving self-limited type of clinical course for the presence of antibody to the hepatitis C virus nucleocapsid (core) protein (p22) expressed by a recombinant baculovirus. These sera were simultaneously examined for antibody to the hepatitis C virus nonstructural protein (C100-3) that is presently used for blood screening worldwide. In three patients, both anti-p22 and anti-C100-3 antibodies were detected, but anti-p22 was detected much earlier. In four patients, only anti-p22 was detected. Two other patients were considered to be hepatitis C virus carriers who had been already infected with hepatitis C virus. In one patient, only anti-C100-3 was detected, and it was transient. In two patients, neither antibody was detected. Anti-p22 was detected in at least one of eight samples of transfused blood. Of the nine samples of donated blood that were positive for anti-p22, only four were positive for anti-C100-3. This new assay detecting the antibody to the p22 protein is thus useful for the serodiagnosis of non-A, non-B hepatitis in the acute phase and for blood screening.

Antigens, Viral↗
PubMed1992

Purification and characterization of an unusually large fatty acid synthase from Mycobacterium tuberculosis var. bovis BCG.

Fatty acid synthase was purified from Mycobacterium tuberculosis var. bovis BCG. The method developed gave a 23% yield of the synthase and also yielded purified mycocerosic acid synthase. The fatty acid synthase is of unusually large size and composed of two 500-kDa monomers. The amino acid composition of the two synthases was not identical; the N-terminus of the fatty acid synthase was blocked, whereas that of the mycocerosic acid synthase was not. Western blot analysis of crude mycobacterial extracts with polyclonal antibodies prepared against each synthase showed a single band in each case with no cross-reactivity with the other synthase. Fatty acid synthase required both NADH (Km, 11 microM) and NADPH (Km, 14 microM). The Km for acetyl-CoA and malonyl-CoA were 5 and 6 microM, respectively. Fatty acids were released from the synthase as CoA esters. A bimodal distribution of fatty acids was obtained at around C16 and C26. The primer utilization also reflects the de novo synthesis and elongation capabilities of the enzyme; acetyl-CoA was the preferred primer but CoA esters up to C8 but not C12 and C14 could serve as primers, whereas C16 was readily used as a primer for elongation. Addition of CoA and CoA ester-binding oligosaccharides caused enhanced release of C16. Since this mycobacterial fatty acid synthase is twice as large as other multifunctional fatty acid synthases, it is tempting to suggest that this synthase represents a head to tail fusion of two fatty acid synthase genes coding for a double size protein with one-half producing C16 acid and the other elongating the C16 acid to a C26 acid. The monomer of fatty acid synthase from M. smegmatis was immunologically similar and equal in size to the synthase from M. tuberculosis.

Acetyl Coenzyme A↗
PubMed1992

Impaired NK response of cancer patients to IFN-alpha but not to IL-2: correlation with serum immunosuppressive acidic protein (IAP) and role of suppressor macrophage.

In vitro NK responses of cancer patients (N = 21) to rIFN-alpha A and rIL-2 were examined. The serum concentration of IAP (immunosuppressive acidic protein) was determined in parallel. Five out of seven patients whose serum IAP contents were within the normal range (270 micrograms/ml to 470 micrograms/ml), had their NK activities significantly augmented by rIFN-alpha A and rIL-2. On the other hand, NK cells from ten out of fifteen patients whose serum IAP concentrations were 650 micrograms/ml or more, were not activated by rIFN-alpha A. NK cells of these fifteen patients yet were capable of responding to rIL-2. NK cells from cancer patients, however, became responsive to rIFN-alpha A by either removal of adherent cells or treatment with indomethacin. Therefore, macrophages in PBMC of cancer patients with high serum IAP levels seem to selectively suppress NK response to rIFN-alpha A by an indomethacin-sensitive mechanisms. It was further shown that PGE2 was not the mediator of this suppression.

Adult↗
PubMed1992

[Effect of tranilast, an anti-allergic drug, on the human keloid tissues].

We studied the inhibitory effects of tranilast, an anti-allergic drug, on the human keloid tissues implanted into the dorsal skin of athymic nude mice and on the growth of keloid fibroblast in vitro. In the keloid tissue-implanted model, tranilast (50-200 mg/kg, p.o.) decreased the weight of the keloid tissue as triamcinolone (25 mg/kg, p.o.) did. Tranilast (200 mg/kg, p.o.) reduced the hydroxyproline content of implanted tissues. Tranilast (3-300 microM) also inhibited the collagen synthesis by keloid fibroblast in vitro. Only a high concentration of tranilast (300 microM) suppressed the glycosaminoglycan synthesis and cell proliferation of keloid fibroblasts. Moreover, tranilast scarcely affected the fibronectin production. Triamcinolone (10 microM) also inhibited glycosaminoglycan synthesis and cell proliferation. These results suggest that the inhibitory effect of tranilast on the keloid tissues is related to its inhibition of the collagen synthesis of fibroblasts. Tranilast would be useful as a therapeutic drug for the treatment of keloids.

Animals↗
PubMed1992

[Effect of tranilast, an anti-allergic drug, on carrageenin-induced granulation and capillary permeability in rats].

We studied the effect of tranilast on the growth of carrageenin-induced granulation and the increase in capillary permeability induced by inflammatory agents in rats. In the carrageenin-induced granulation model, tranilast (50 or 100-200 mg/kg, p.o.) decreased significantly and dose-dependently the weight and the hydroxyproline content of the granulation tissue. Tranilast, however, showed no effect on the healing day of locally wounded dorsal skin of rats. Triamcinolone (10 mg/kg, p.o.) also showed an inhibitory effect on the carrageenin-induced granulation model. Tranilast (50-400 mg/kg, p.o.) dose-dependently inhibited the enhancement of capillary permeability induced by the Ca ionophore A23187, bradykinin and xanthine oxidase. Moreover, tranilast (30 and 300 microM) suppressed superoxide production induced by FMLP in human neutrophils, but did not act as a superoxide scavenger. Considering that hypertrophic scar and keloid are conditions characterized by abnormal cell proliferation and excessive collagen accumulation accompanied with itch and pain, these results suggest that tranilast is useful as a therapeutic drug for hypertrophic scars and keloids.

Adult↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

[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↗
PubMed1992

[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↗
PubMed1992

[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↗
PubMed1992

[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↗