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Biomedical subjects

M Sakagami

Publications and source records attributed to M Sakagami.

At least 55 records · Page 3Linked to original sources
PubMed1998

Targeted disruption of the MyD88 gene results in loss of IL-1- and IL-18-mediated function.

MyD88, originally isolated as a myeloid differentiation primary response gene, is shown to act as an adaptor in interleukin-1 (IL-1) signaling by interacting with both the IL-1 receptor complex and IL-1 receptor-associated kinase (IRAK). Mice generated by gene targeting to lack MyD88 have defects in T cell proliferation as well as induction of acute phase proteins and cytokines in response to IL-1. Increases in interferon-gamma production and natural killer cell activity in response to IL-18 are abrogated. In vivo Th1 response is also impaired. Furthermore, IL-18-induced activation of NF-kappaB and c-Jun N-terminal kinase (JNK) is blocked in MyD88-/- Th1-developing cells. Taken together, these results demonstrate that MyD88 is a critical component in the signaling cascade that is mediated by IL-1 receptor as well as IL-18 receptor.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Failure of forskolin to elevate the endocochlear potential in experimental endolymphatic hydrops of the guinea pig.

The effect of forskolin (FSK) on the endocochlear potential (EP) in scala media (SM) was examined in experimental endolymphatic hydrops of the guinea pig. Two weeks after obliteration of the endolymphatic sac the EP of hydroptic ears and that of the contralateral control ears were measured by means of microelectrodes. The perfusion of scala vestibuli (SV) with FSK (200 microM) produced EP elevation in the contralateral control ears but failed to do so in the experimental hydroptic ears. Histological examination of experimental endolymphatic hydrops showed mild hydrops with intact appearance of outer and inner hair cells, and the stria vascularis. The mechanism underlying the failure of FSK to elevate the EP in experimental endolymphatic hydrops is discussed.

Animals↗
PubMed1997

Expression of highly polysialylated NCAM (NCAM-H) in developing and adult chicken auditory organ.

Neural cell adhesion molecule (NCAM) is highly polysialylated (NCAM-H) in developing tissues, and recent findings suggest that NCAM-H is more essential for neural development than poorly sialylated NCAM (NCAM-L). In order to understand the precise role of NCAM-H in developing and adult inner ears, the immunohistochemical localization of NCAM-H in developing and adult chicken inner ears was examined using a monoclonal antibody which is only specific for NCAM-H. Immunoreactivity of NCAM-H was initially observed on acoustic ganglion at stage 24, when peripheral (afferent) fibers begin to emerge from the ganglion cells. At stage 38, when peripheral fibers form synapses with hair cells, NCAM-H was observed on peripheral fibers and the base of hair cells in the auditory epithelium. At stage 42, NCAM-H on nerve fibers disappeared, and only some acoustic ganglion cells were still positive for NCAM-H. This immunostain on ganglion cells was retained after birth. These data are consistent with the hypothesis that NCAM-H specifically regulates the afferent nerve fibers' growth and synaptogenesis with hair cells during inner ear development and may be associated with processing of auditory information and neuronal plasticity.

Animals↗
PubMed1997

Hepatic accumulation of glutamic acid branched neogalactosyllipid modified liposomes.

We synthesized branched type galactosyllipid derivatives for liposome modification for the targeting of asialoglycoprotein receptors on the surface of liver cells. Galactose was coupled to the alpha- and gamma-carboxyl groups of glutamic acid via a triethyleneglycol spacer, then this glutamic moiety was bound to the lipid anchor. Ricinus communis agglutinin (RCA120) induced the agglutination of liposomes modified with mono-, bi- and tri-antennary neogalactosyllipid. With the bi- or tri-antennary derivatives, agglutination was observed at fewer galactosyl residues on the liposomes. We examined the effect of the branching structure in vivo. The difference in accumulation of liposomes between non-branched type neogalactosyllipid and branched type neogalactosyllipid was not large. Liver accumulation of liposomes depended on the galactosyl residues. The number of galactosyl residues was more effective for accumulation in the liver than for branching. We studied the effect of asialofetuin preinjection on the hepatic accumulation of neogalactosyllipid modified liposomes. Hepatic accumulation of liposomes was inhibited by preinjection of asialofetuin. The effect of preinjection was almost equal among the ligands. These results show that the saccharide density on the liposome surface seemed to be a more important factor than the branching structure of the ligand for liver targeting.

Animals↗
PubMed1997

Synthesis and application of neoglycolipids for liposome modification.

We synthesized various glycolipid derivatives and examined the in vivo behaviors of liposomes modified with these novel glycolipid derivatives. Gal-t-psa (1,¿8-(2-hexadecyloctadecanoylamido)-3,6-dioxaoctyl¿-beta-D- galactoside), Lac-t-psa (3, 8-(2-hexadecyloctadecanoylamido)-3,6-dioxaoctyl beta-D-lactoside) and GalNAc-t-psa (4, 8-(2-hexadecyloctadecanoylamido)-3,6-dioxaoctyl 2-acetamido-beta-D-galactopyranoside) modified liposomes were recognized by the liver. Lac-t-psa (3) modified liposome was accumulated to the highest degree, followed by GalNAc-t-psa (4) modified liposome and then Gal-t-psa (1) modified liposome. The intrahepatic distributions of Gal-t-psa (1), GalNAc-t-psa (4), Glc-t-psa (2, 8-(2-hexadecyloctadecanoylamido)-3,6-dioxaoctyl beta-D-glucopyranoside) and Lac-t-psa (3) modified liposomes were investigated. GalNAc-t-psa (4) and Lac-t-psa (3) modified liposome were accumulated to greater extents than Gal-t-psa (1) modified liposome in hepatic parenchymal cells. The intrahepatic distribution of these liposomes showed that Lac-t-psa (3) and GalNAc-t-psa (4) were preferable to Gal-t-psa (1) for the selective delivery of liposomes to hepatic parenchymal cells.

Animals↗
PubMed1997

Indonesian medicinal plants. XIX. 1) Chemical structures of four additional resin-glycosides, mammosides A, B, H1, and H2, from the tuber of Merremia mammosa (Convolvulaceae).

Four new resin-glycosides, named mammosides A (10), B (11), H1 (12), and H2 (13), were isolated from the tuber of Merremia mammosa (Convolvulaceae), a Jamu raw material. Their chemical structures have been elucidated on the bases of chemical and physicochemical evidence, including synthesis of a glycosidic acid designated as mammoside I.

Carbohydrate Sequence↗
PubMed1997

[Sensorineural hearing loss caused by middle ear surgery].

It is well known that sensorineural hearing loss rarely occurs after middle ear surgery. Five cases of postoperative sensorineural hearing loss were reviewed. These operations amounted to 0.9% of all middle ear operations in which the first author was involved. The causes of hearing loss were believed to be labyrinthitis through the fistula in cholesteatoma case 1, and acoustic trauma from the bone-cutting burr in cases 2 and 3. In cases 4 and 5 postoperative sensorineural hearing loss occurred several months after stapes surgery and the causes of hearing loss were unknown. On the basis of the available literature discussion focused on management of labyrinthine fistula, the acoustic effect of the bone-cutting burr and the possibility of sensorineural hearing loss caused by stapes surgery.

Aged↗
PubMed1997

Chemohormonal therapy for malignant melanomas of the nasal and paranasal mucosa.

We present three cases of primary malignant melanoma of the nasal or paranasal mucosa that were successfully treated by chemohormonal therapy using tamoxifen (TAM), an anti-estrogen agent. All of the patients showed good responses. TAM is widely known to be an anti-estrogen chemotherapeutic agent in the treatment of breast cancer and is thought to exert its anti-neoplastic effect in breast cancer tissues by competing with estrogen for estrogen receptors. The mechanism of the effect of TAM in malignant melanoma is not yet known. Although its anti-neoplastic mechanism requires further exploration, we believe that chemohormonal therapy may become important in multidisciplinary treatment of malignant melanoma of the nasal and paranasal mucosa.

Aged↗
PubMed1997

[Endoscopic transthoracic sympathectomy for angina pectoris: a case report].

We performed endoscopic transthoracic sympathicotomy (ETS) for angina pectoris in a 77-year-old female. She had multiple coronary disease of a history of failed percutaneous transluminal coronary angioplasty (PTCA). Bilateral ETS of Th2 to Th5 was carried out under general anesthesia without surgical complication, hemodynamic change and ECG change. Postoperatively she was free from angina and increased working capacity. ST depression on ECG was remarkably improved and the increase of heart rate and systolic blood pressure was suppressed on exercise test after a month of ETS. The effect of ETS to angina pectoris was suspected not to relieve anginal pain but also to reduce myocardial oxygen demand on exercise. We conclude that ETS is a safe, simple and low invasive procedure and it can be done in patients who are judged unsuitable for coronary artery bypass grafting (CABG) or PTCA.

Aged↗
PubMed1996

Localization of bone morphogenetic protein-4 messenger RNA in developing mouse cochlea.

Bone morphogenetic protein-4 (BMP-4) is a cytokine that belongs to the TGF-beta superfamily. It has been implicated that it plays an important role during embryogenesis including epithelial-mesenchymal interactions and mesenchymal cells condensation. To investigate whether BMP-4 is involved in the embryogenesis of the inner ear, we performed in situ hybridization at various stages of the developing inner ear of mice. BMP-4 mRNA was detected only in the developmental stage. Its initial expression was detected in part of the otic vesicle at 9 days post-coitum (PC). As development proceeded, the hair cells of the cochlear duct were morphologically distinguishable. and BMP-4 expressing cells were found in Claudius cell region at 16 days PC. At this stage, the signal was most intense during development and the structure notably changed under the expressing cells. Mesenchymal cells were assembled and condensed underneath the BMP-4-expressing cells. The basilar membrane, with a rich extracellular matrix and elasticity, would be produced in the area between the Claudius' cells and condensed mesenchymal cells. Previous reports support the notion that BMP-4 expressed in the epithelium causes mesenchymal cell condensation and induces a structure with elasticity. In the developing cochlea. BMP-4 may be involved in the condensation and differentiation of the mesenchymal cells as well as basilar membrane formation. BMP-4 might be an essential factor for the normal development of the basilar membrane.

Animals↗
PubMed1996

Impaired Ranvier node sodium-potassium adenosine triphosphatase may induce facial palsy.

To clarify the part of the neuron essential for myelinated nerve conduction, the cytochemical localization of potassium ion (K+)-dependent p-nitrophenylphosphatase (K-NPPase) activity was investigated in the normal and reserpine-treated facial nerve of guinea pigs. In the normal animals, K-NPPase activity was localized to the internodal axolemma and Schmidt-Lanterman incisures. In the Ranvier nodes, enzyme activity was observed along the paranodal and nodal axolemma. In reserpinized nerves, K-NPPase activity was absent along the internodal axolemma and Schmidt-Lanterman incisures. In the Ranvier nodes, however, enzyme activity was detectable only in the nodal axolemma. The reserpinized animals demonstrated no evidence of facial palsy. Because K-NPPase is essential for nerve conduction, these results indicate that the location of enzyme activity in reserpinized animals, namely the nodal axolemma, may be of prime importance in saltatory nerve conduction.

Animals↗
PubMed1996

Compensatory enlargement of angiographically normal coronary segments in patients with coronary artery disease. In vivo documentation using intravascular ultrasound.

Intravascular ultrasound (IVUS) frequently reveals plaque formation at sites with a normal angiographic appearance. However, whether angiographically normal coronary arteries undergo adaptive expansion in vivo remains uncertain. The authors studied 12 patients (11 men, 1 woman; mean age fifty-three +/- ten years [mean +/- SD]) with focal coronary stenosis. Sixty IVUS images from angiographically normal coronary segments were analyzed (14 left main, 44 left anterior descending, and 2 left circumflex coronary arteries). The mean percent area stenosis was 36 +/- 5% and the circular shape factor of the lumen cross section averaged 0.97 +/- 0.02. Both total arterial area and internal elastic lamina area increased as the plaque area expanded (y = 2.13x + 8.07, r = 0.87, P = 0.0001; y = 2.06x + 4.57, r = 0.87, P = 0.0001, respectively), suggesting that for every 1 mm2 increase in plaque area, the total arterial area increased by approximately 2.13 mm2 and the internal elastic lamina area increased by approximately 2.06 mm2. The lumen area also increased as the plaque area expanded (y = 1.06x + 4.57, r = 0.68, P = 0.0001), suggesting that for every 1 mm2 increase in plaque area, the lumen area increased by approximately 1.06 mm2. The medial area did not correlate with the plaque area (r = 0.15, P = 0.26). Thus, compensatory enlargement precedes development of angiographically, detectable coronary atherosclerosis. Furthermore, in early stages of atherosclerosis, arterial enlargement may overcompensate for plaque area. The reduction of the total medial mass does not appear to contribute to the mechanism of compensatory enlargement.

Adaptation, Physiological↗
PubMed1996

Cytochemical effects of in vitro dopamine treatment on the Na-KATPase activity in strial marginal cells.

Dopamine is often used clinically for the treatment of patients with shock. In a previous study, the Na-KATPase (K-NPPase) activity of strial marginal cells was inhibited after the repeated in vivo administration of dopamine hydrochloride. In the present study, the K-NPPase activity of strial marginal cells was determined using a cerium-based cytochemistry after an in vitro incubation with dopamine. The enzyme reaction product was found in untreated normal strial marginal cells, but it was almost completely undetectable after an in vitro treatment with 10 mM dopamine. This finding suggested that dopamine directly inhibited the Na-KATPase activity of strial marginal cells, and that these cells might have a dopamine receptor.

Adrenergic Agents↗
PubMed1996

[Chemohormonal therapy for malignant melanomas].

The management of malignant melanoma of the head and neck is controversial in view of the poor prognosis. Although radical surgery has been proposed as the best therapy for mucosal malignant melanoma, it has seldom been performed because of the extent of tumors and anatomical difficulties. In spite of testing various methods such as chemotherapy, radiotherapy and immunotherapy, that have been suggested for treatment of this malignant disease, there are still no well established effective therapies. We attempted chemohormonal therapy including TAM (Tamoxifen), an anti-estrogen agent, in six patients with primary malignant melanoma from 1993 to 1996. Three patients had a complete response, two had a partial response, and one showed no change. The toxicity in this protocol was found to be low. Generally, the patients showed good responses to chemohormonal therapy. TAM has been previously best known as a therapeutic agent for mammary cancer. Its anti-cancer effect is thought to be due to the anti-estrogen activity revealed by binding to the estrogen receptor competitively with estrogen in the tumor tissue. However, the mechanism of the action of TAM against malignant melanoma has not been clarified yet. Although its anti-cancer mechanism should be further explored, it is suggested that this chemohormonal therapy could occupy a very important position in the multidisciplinary therapy of malignant melanoma of the head and neck.

Aged↗
PubMed1996

[Tympanoplasty on only hearing ears].

Tympanoplasty on only hearing ears was performed on 11 patients in Osaka University Hospital and Osaka Rosai Hospital during 1986 1994; this was 0.68% of all cases of middle ear surgery. The patients consisted of 5 with cholesteatoma, 5 with chronic otitis media and 1 with cholesterin granuloma. The mean age was 47.6 years (13-68 years) and the mean follow-up period was 2 years and 7 months (6 months-4 years). Postoperative hearing results was obtained in 9 patients (81.8%) according to the criteria of Otology Japan (1987), and all ears were dry at the final examination. Compared with the preoperative hearing level, postoperative hearing level showed improvement in 3 cases, not in 7 cases (within difference of 5 dB) and deterioration by 10-15 dB in 1 case. Although indications for surgery on only hearing ears are still controversial, we suggest the following: 1) patients with cholesteatoma should be operated on in the ordinary way; 2) patients with chronic otitis media should be operated on only by myringoplasty; 3) all patients must be operated on very carefully by skillful surgeons.

Adolescent↗
PubMed1995

Hair cell regeneration in the chick inner ear following acoustic trauma: ultrastructural and immunohistochemical studies.

The regeneration of hair cells in the chick inner ear following acoustic trauma was examined using transmission electron microscopy. In addition, the localization of proliferation cell nuclear antigen (PCNA) and basic fibroblast growth factor (b-FGF) was demonstrated immunohistochemically. The auditory sensory epithelium of the normal chick consists of short and tall hair cells and supporting cells. Immediately after noise exposure to a 1500-Hz pure tone at a sound pressure level of 120 decibels for 48 h, all the short hair cells disappeared in the middle region of the auditory epithelium. Twelve hours to 1 day after exposure, mitotic cells, binucleate cells and PCNA-positive supporting cells were observed, and b-FGF immunoreactivity was shown in the supporting cells and glial cells near the habenula perforata. Spindle-shaped hair cells with immature stereocilia and a kinocilium appeared 3 days after exposure; these cells had synaptic connections with the newly developed nerve endings. The spindle-shaped hair cell is considered to be a transitional cell in the lineage of the supporting cell to the mature short hair cell. These results indicate that, after acoustic trauma, the supporting cells divide and differentiate into new short hair cells via spindle-shaped hair cells. Furthermore, it is suggested that b-FGF is related to the proliferation of the supporting cells and the extension of the nerve fibers.

Acoustic Stimulation↗
PubMed1995

Endocytosis and transepithelial transport of endolymph in the endolymphatic sac.

The fate of cationized ferritin (CF) injected into the endolymphatic space of the endolymphatic sac was observed by transmission electron microscopy. At 10 min after the injection, CF particles bound to the apical plasma membrane of epithelial cells of the sac and were then endocytosed with coated pits. However, they never passed through the junctional complexes between the epithelial cells. At 30 min after the injection, the CF particles were transferred to endosomes and lysosomes by small vesicles of 100-150 nm in diameter. CF particles were also found in small vesicles close to Golgi cisternae and in multivesicular bodies. Acid phosphatase positive lysosomes were found close to endosomes containing CF particles. In addition, a small fraction of the small vesicles containing CF particles became inserted into the basolateral plasma membrane. At 60 min after the injection, many CF particles were found in acid phosphatase positive secondary lysosomes. These observations suggest that endocytosis of endolymph is actively performed by the epithelial cells of the sac, and transepithelial vesicular transport across the epithelial cells occurs.

Acid Phosphatase↗