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Biomedical subjects

S Ikeda

Publications and source records attributed to S Ikeda.

At least 559 records · Page 31Linked to original sources
PubMed1994

Localization of the gene for Darier disease to a 5-cM interval on chromosome 12q.

Darier disease is an autosomal dominant abnormality of epidermal differentiation characterized clinically by the presence of hyperkeratotic papules on the skin and histologically by the loss of cell cohesion and by disorderly keratinization. Two groups recently found evidence that the gene whose mutations underlie this disease is located at chromosome 12q23-q24.1, a site on chromosome 12 that clearly is distal to the type II keratin gene cluster. We report here evidence for sublocalization to a 5-cM region of that site in an additional ten families of European and Middle Eastern ancestry with a combined lod score in excess of 20.

Adult↗
PubMed1994

Aberrations of the tumor suppressor p53 gene and p53 protein in solar keratosis in human skin.

Aberrations of the p53 gene in 27 solar keratoses were examined by the polymerase chain reaction and single-strand conformation polymorphism and DNA sequencing analyses. In a series of Japanese patients, eight of 27 cases (30%) of solar keratosis showed structural abnormalities of the p53 gene. Six of eight aberrations of p53 gene were determined to be single nucleotide substitutions, and five of these were located at a dipyrimidine site. In solar keratosis, noticeable mutations were C to T in three cases, and one each of C to A and T to C nucleotide changes. p53 protein was detected immunohistochemically in the nuclei of six of 27 cases (22%) of solar keratosis. Nuclear staining for p53 protein was only significantly correlated with the presence of missense mutation of p53 gene (p < 0.01). Aberrations of the p53 gene in solar keratosis may be a marker to predict early cancerous lesions.

Base Sequence↗
PubMed1994

Successful surgical management and long-term follow-up of epidermolysis bullosa.

BACKGROUND: Esophageal stenosis and hand deformity are serious complications of recessive dystrophic epidermolysis bullosa that influence the prognosis of patients. To control such complications we have used surgical treatments with favorable results. Additional objectives were to summarize the results of long-term follow-up. METHODS: Six patients with esophageal stenosis and nine patients (13 hands) with hand deformity (contracted fingers, mitten-like deformity) were treated surgically after anemia and malnutrition were corrected by intravenous iron infusion, high-energy diet, and blood transfusion. As intubation was contraindicated, topical anesthesia was used (eg., lidocaine spray to the nasopharyngeal mucosa for esophageal dilatation and brachial block, ketamine drip, and nitrous oxide inhalation for reconstruction of contracted fingers). We established a new method for esophageal dilatation using a microvasive rigiflex balloon catheter. This catheter was advanced to the stenotic area under radiography and then expanded by injecting contrast medium into the balloon. For reconstruction of hand deformities, the epidermal glove was initially peeled off, and then the combined digits separated carefully by hand. If the release of the contracture was not sufficient, a skin incision was made avoiding injury to nerves and blood vessels. Any skin defects that appeared after the release of the contracture were covered with skin grafts taken from the abdominal wall. K-wire fixation was used to maintain the extended position of the fingers. Three weeks after the operation, the K-wires were removed and rehabilitation was commenced. RESULTS: The esophageal stenosis was successfully dilated with the balloon catheter; in all six cases the dysphagia was relieved immediately. There was no recurrence in any of the patients on long-term follow-up. After reconstruction of the hand, daily activity improved in 12 of the 13 hands. The remaining hand was difficult to reconstruct due to severe mutilation and bone deformity. During follow-up, 6 of the 12 hands maintained successful reconstruction, whereas the remaining 6 hands showed slight to moderate recontraction of the fingers. CONCLUSION: Esophageal dilatation with a balloon catheter is safer and has fewer side effects compared to other surgical procedures. This method can provide favorable results and can be carried out repeatedly in a short time. Daily and social activities of patients can be improved upon reconstruction of hand deformities.

Adolescent↗
PubMed1994

In vitro and in vivo inhibition of ortho- and paramyxovirus infections by a new class of sulfonic acid polymers interacting with virus-cell binding and/or fusion.

A series of sulfonic acid polymers were shown to be potent and selective inhibitors of respiratory syncytial virus (RSV) and influenza A virus. The compounds inhibit the replication of RSV and influenza A virus in HeLa and MDCK cells, at concentrations of 0.16 and 4.0 micrograms/ml, respectively, and are nontoxic to growing cells at concentrations of > 100 micrograms/ml. The mode of antiviral action of the sulfonic acid polymers can be ascribed to inhibition of virus-cell fusion (for influenza A virus) or inhibition of both virus-cell binding and fusion (for RSV). The sulfonic acid prototype PAMPS [poly(2-acrylamido-2-methyl-1-propanesulfonic acid)], when administered intranasally to mice as a single dose of 10 or 50 mg per kg of body weight at the time of infection, completely inhibited influenza A virus replication (in lungs) and virus-associated lung consolidation in immunocompetent mice and completely protected NMRI and SCID (severe combined immune deficiency) mice against influenza A virus-associated mortality. When administered 1 h before or after virus inoculation, no protective effect was observed at a dose of 10 or 100 mg/kg. Sulfonic acid polymers exert selective inhibitory effects on RSV and influenza A virus replication.

Animals↗
PubMed1994

Contraction and depolarization induced by fetal bovine serum in airway smooth muscle.

We investigated the effects of fetal bovine serum (FBS) on the resting membrane potential and muscle tone of canine airway smooth muscles using tension recording and microelectrode methods. At concentrations > 0.1%, FBS induced a sustained increase in muscle tone. At concentrations > 1%, FBS depolarized the resting membrane potential of dog trachea in a dose-dependent manner. When FBS was dialyzed, it failed to induce a sustained increase in muscle tone or to depolarize the membrane, indicating that FBS contained factor(s) that induced contraction of dog airway smooth muscles. When FBS was dialyzed against distilled water, the outer solution which was freeze dried and then reconstituted (> 1% in original vol) induced a sustained increase in muscle tone, indicating that FBS contained dialyzable factor(s) that increased muscle tone and depolarized the resting membrane potential of dog airway smooth muscles. Methysergide (10(-6) M) or cyproheptadine (10(-6) M), nonspecific antagonists to serotonin receptors, 5-hydroxytryptamines (5-HT1 and 5-HT2), markedly reduced the FBS-induced increase in the muscle tone to approximately 20% of the original value but did not abolish the response. On the other hand, methysergide (10(-6) M) completely suppressed the increase in the muscle tone evoked by peak fractions obtained by application of the dialysate of FBS or 5-HT to a C18 reverse-phase column, indicating the peak fractions contained only 5-HT. These observations indicate that FBS contained 5-HT and an unknown factor(s) responsible for increase in the muscle tone of the airway smooth muscle induced by FBS.

Animals↗
PubMed1994

Ultrastructural localization of the three major basement membrane components--type IV collagen, heparan sulfate proteoglycan and laminin--in human membranous glomerulonephritis.

Membranous glomerulonephritis (MN) is characterized by the presence of subepithelial immune complexes and thickening of the glomerular basement membrane (GBM). Immune complexes are recognized as subepithelial electron-dense deposits (EDDs) by electron microscopy. We used immunogold electron microscopy to detect the GBM components--type IV collagen, heparan sulfate proteoglycan (HS-PG) and laminin--in thickened GBM, and studied the relationship between immune complexes and these GBM components. We demonstrate that the three major basement membrane components are distributed throughout the newly synthesized GBM. These findings suggest that type IV collagen, HS-PG, and laminin together comprise the spike-like structures and the newly synthesized GBM-like matrix in the thickened GBM of idiopathic MN and membranous lupus nephritis. The newly constructed matrix in the GBM appears to be composed of nearly normal GBM. In type IV collagen, the alpha 1-chain was rarely present on the newly synthesized basement membrane in the lamina rara externa, while alpha 3-chain was present on the subepithelial newly synthesized basement membrane. HS-PG was found within EDDs in membranous lupus nephritis. This suggests that anti-DNA antibody may cross-react with the HS-PG component of the GBM and thus form a subepithelial immune complex.

Adult↗
PubMed1994

Pro-carboxypeptidase R cleaves bradykinin following activation.

Arginine carboxypeptidase (CPR) is a labile enzyme present in human serum which is unrelated to carboxypeptidase N. In this study we demonstrate that CPR exists in a precursor form in plasma and can be converted to the active form by trypsin and presumable trypsin-like enzymes. The trypsin-generated active form can not only cleave a small synthetic substrate, hippuryl-L-arginine, but can remove terminal arginine from bradykinin.

Bradykinin↗
PubMed1994

Prenatal diagnosis of epidermolysis bullosa: first successful trial in Asia.

Prenatal diagnosis of epidermolysis bullosa (EB) using fetal skin biopsy specimens has been successfully performed in Europe and America, but this technique has not previously been attempted in Asia. For the first time in Asia, we attempted to make a prenatal diagnosis of EB in a high-risk fetus by fetal skin biopsy. A skin biopsy was obtained from the fetus at risk of gravis type junctional epidermolysis bullosa of Herlitz. The biopsy specimen was studied by electron microscopy and immunohistochemistry using various monoclonal antibodies against the epidermal basement membrane zone (BMZ). There were no ultrastructural abnormalities in the BMZ, including the hemidesmosomes. Indirect immunofluorescence showed normal expression of GB3 antigen. The pregnancy was continued, and a normal, healthy infant was born. The prenatal diagnosis of epidermolysis bullosa is now available in Tokyo. This clinical diagnostic service is available to families from various parts of Asia.

Biopsy, Needle↗
PubMed1994

Effects of epithelial cell supernatant on membrane potential and contraction of dog airway smooth muscles.

We investigated the effects of cultured epithelial cells and supernatants on resting membrane potential and excitatory neuroeffector transmission in smooth muscle cells of dog trachea and bronchioles. The mean resting membrane potential of the mucosa-free tracheal smooth muscle cells was -59.5 +/- 1.5 mV (+/- SD). Application of cultured epithelial cells (> 2.5 x 10(5) cells/ml) hyperpolarized the membrane, resulting in a potential of -64.5 +/- 1.7 mV. The supernatant of the cultured epithelial cells also increased the resting membrane potential of the mucosa-free tracheal smooth muscle cells by 4 to 9 mV. These hyperpolarizing actions were not modified by indomethacin (10(-5) M), l-NG-nitroarginine (10(-5) M), or oxyhemoglobin (10(-5) M), but were inhibited by glibenclamide (10(-6) M). The supernatants of the cultured epithelial cells completely or partially suppressed the contractile response of epithelium-denuded bronchioles to electrical field stimulations and suppressed the amplitude of excitatory junction potentials of the trachealis evoked by electrical field stimulations. Indomethacin prevented the inhibitory effect of supernatants on the amplitude of twitch contractions and excitatory junction potentials and markedly suppressed supernatant-associated inhibition of the excitatory neuroeffector transmission. Furthermore, indomethacin with AA861, a lipoxygenase inhibitor, completely suppressed this effect. Our findings suggest that cultured airway epithelial cells spontaneously release at least two factors. One factor selectively modulates the resting membrane potential, and the other inhibits the excitatory neuroeffector transmission.

Animals↗
PubMed1994

Adult GM1 gangliosidosis: immunohistochemical and ultrastructural findings in an autopsy case.

We report neuropathologic findings for a 66-year-old Japanese man with adult/chronic GM1 gangliosidosis whose main clinical symptoms were speech and gait disturbance attributable to dystonia with rigidity. He was a homozygote for the 51isoleucine (ATC)-->threonine (ACC) mutation in the beta-galactosidase gene. Neuronal loss and intracytoplasmic storage were most prominent in the caudate nucleus and putamen and, to a lesser degree, in the amygdala, globus pallidus, and Purkinje cells in the cerebellum. Other areas of the CNS were relatively spared. We believe that this selective neuronal involvement in the CNS is characteristic of adult/chronic GM1 gangliosidosis and that it reflects a more active turnover of GM1 ganglioside in the affected areas than elsewhere in the CNS.

Acetylgalactosamine↗
PubMed1994

Suppressive effects of the anti-allergic drugs, tranilast and azelastine, on the lysophosphatidylserine-dependent activation of rat mast cells.

Anti-allergic drugs, tranilast and azelastine, were examined for their effects on lysophosphatidylserine (lysoPS)-dependent histamine release from rat mast cells. Although both compounds suppressed the histamine release in a dose-dependent manner, the inhibition was affected by lysoPS concentration differently. In the presence of an increasing concentration of lysoPS, the suppressive effect of tranilast decreased. The inhibition by azelastine, however, was independent of the concentration of lysoPS. The findings suggest that these two drugs inhibit lysoPS-depedent histamine release through essentially different routes.

Animals↗
PubMed1994

Variability of beta-amyloid protein deposited lesions in Down's syndrome brains.

An immunohistochemical study was carried out on the brains of 7 adult Down's syndrome cases (ages 31 to 62) using antibodies to beta-protein, beta-amyloid protein precursor and tau-protein. Variable forms of beta-protein deposited lesions (including senile plaques and cerebrovascular amyloidosis) were observed in extensive areas of the neocortex of all cases and coexistence of both beta-protein amyloid fibrils and beta-amyloid protein precursors was also seen in some of these lesions. Moreover, 3 cases at an advanced stage showed a few plaque-like lesions with beta-protein immunoreactivity in the white matter. The following temporal morphological change is suggested for the pathogenesis of Alzheimer's disease: senile plaque undergo sequential structural changes and beta-protein amyloid deposits in the form of "early plaque" precede the development of tau-immunoreactive neurofibrillary degeneration.

Adult↗
PubMed1994

The decrement of muscarinic receptor-mediated calcium influx by overexpression of APP in a mouse cholinergic cell line.

The effects of beta-amyloid precursor protein (APP) overexpressing on cell metabolisms of cholinergic neuronal hybridoma cell line (SN49) were examined. The cells stably overexpressing APP contained higher amount of GTP binding protein Go and cytosolic inactive protein kinase C epsilon, and showed less Ca2+ influx through muscarinic acetylcholine receptor ml compared to original and mock cells which had been transfected with a vector alone. The contents of sn-1, 2-diacylglycerol and cyclic AMP were also reduced in the APP transfectants, although the similar changes were observed in the mock cells. These findings strongly suggest that the overexpression of APP affect the transient receptor-mediated ion channel and calcium-related cell metabolisms in neuronal cells.

Acetylcholine↗
PubMed1994

Hearing recovery and vestibular symptoms in patients with sudden deafness and profound hearing loss.

Audiometric data from 76 patients with unilateral sudden deafness and hearing loss of 80 dB or more were studied to statistically assess the relationship between vestibular findings (vertigo and/or dizziness, nystagmus, canal paresis) and hearing recovery in various frequency ranges. Hearing recovery in patients with vertigo and/or dizziness (V(+)) was much poorer than in patients without such findings (V(-)). Concerning hearing recovery in the high frequency range, a significant statistical difference was evident between the V(+) and V(-) group. There were no statistically significant differences in hearing recovery between patients with spontaneous nystagmus or canal paresis and those without.

Adult↗
PubMed1994

Host defense mechanisms against murine cytomegalovirus infection induced by poly I:C in severe combined immune deficient (SCID) mice.

The role of host defense mechanism against murine cytomegalovirus (MCMV) infection in mice with severe combined immunodeficiency (SCID) was investigated using polyinosinic:polycytidylic acid (poly I:C) as a nonspecific stimulator of the immune system. When administered ip at doses of 3.7 or 15 mg/kg 18 hr prior to infection of SCID mice with 10(3) or 10(4) plaque-forming units of MCMV, poly I:C significantly increased the animals' life span. Poly I:C enhanced, in a dose-dependent manner (0.01-1 mg/kg), the peritoneal natural killer (NK)-cell activity and macrophage activity of SCID mice. When SCID mice were pretreated with anti-asialo GM1 antibody (against NK cells) or anti-Mac1 antibody (against macrophages), poly I:C failed to stimulate the activity of NK cells and macrophages. Intraperitoneal administration of poly I:C also induced both early (2 hr) and late (18 hr) type interferon (IFN) in the peritoneal fluid and blood. The IFN-inducing activity of polyl:C was not affected by pretreatment of the mice with anti-asialo GM1 or anti-Mac1 antibody. Poly I:C also caused a significant but less pronounced increase in the life span of MCMV-infected SCID mice in which the NK cells or macrophages had been depleted by treatment with anti-asialo GM1 or anti-Mac1 antibody, respectively. These results suggest that poly I:C-induced interferon as well as activation of NK cell and macrophages contribute to the host defense mechanism against MCMV infection in SCID mice.

Animals↗