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K Komai

Publications and source records attributed to K Komai.

At least 37 records · Page 2Linked to original sources
PubMed2000

Recombinant calcium channel is recognized by Lambert-Eaton myasthenic syndrome antibodies.

The authors studied sera from 36 patients with Lambert-Eaton myasthenic syndrome (LEMS) by immunoblots using the recombinant protein derived from the DNA sequence encoding for the domain III S5-S6 linker of the P/Q-type voltage-gated calcium channel al subunit. The results of 18 patients were positive for antibodies to this recombinant protein. The results of 2 of 10 patients with lung cancer without LEMS were also positive.

Antibodies↗
PubMed2000

Peripheral sympathetic dysfunction in patients with Parkinson's disease without autonomic failure is heart selective and disease specific. taki@med.kanazawa-u.ac.jp.

UNLABELLED: The study was undertaken to investigate by means of iodine-123-labelled metaiodobenzylguanidine (MIBG) scintigraphy the peripheral sympathetic function in patients with Parkinson's disease (PD) without autonomic failure and in patients with related neurodegenerative diseases with parkinsonism. Seventy patients (33 men and 37 women, mean age 63+/-9.7 years) with parkinsonism and ten control subjects underwent MIBG scintigraphy. Of these 70 patients, 41 were diagnosed as having idiopathic PD, 9 multiple system atrophy (MSA), 6 progressive supranuclear palsy (PSP) and 2 corticobasal degeneration (CBD); the remaining 12 were diagnosed as having neurodegenerative disease with parkinsonism (P-nism) that did not meet the diagnostic criteria of any specific disease. Cardiac planar and tomographic imaging studies and subsequent whole-body imaging were performed 20 min and 3 h after the injection of 111 MBq MIBG. The early MIBG heart to mediastinum (H/M) ratio in PD (1.61+/-0.29) was significantly lower than that in the control group (2.24+/-0.14, P<0.01), P-nism (2.15+/-0.31, P<0.01), MSA (2.08+/-0.31, P<0.05) and PSP (2.30+/-0.24, P<0.01). The delayed H/M ratio in PD (1.47+/-0.34) was also significantly lower than that in the control group (2.37+/-0.14, P<0.01), P-nism (2.13+/-0.38, P<0.01), PSP (2.36+/-0.36, P<0.01) and MSA (2.17+/-0.36, P<0.01). In patients with PD, early and delayed H/M ratios were significantly decreased in disease stages I, II and III (established using the Hoehn and Yahr criteria) as compared with control subjects, and there were no significant differences among the stages. Only PD showed a significantly higher washout rate (WR) than that in the control subjects (27%+/-8.0% vs. 11%+/-4.2%, P<0.01). Early and delayed uptake ratios of the lung, parotid gland, thyroid gland, liver and femoral muscles in each of the patient groups were not significantly different from those in control subjects. Only the early and delayed uptake ratios of the lower leg muscles in MSA were significantly lower than those in the control group (P<0.05). IN CONCLUSION: In patients with PD without autonomic failure, only cardiac MIBG uptake was severely reduced in the earliest phase of the disease (stage I). Parkinsonian syndromes other than PD did not demonstrate significant reduction in MIBG uptake in any organs except for the lower legs in MSA. In patients with PD without autonomic failure, reduction in MIBG uptake occurs selectively in the heart; this is considered to be a specific finding for PD and useful for the differential diagnosis of the parkinsonian syndromes.

3-Iodobenzylguanidine↗
PubMed2000

Lambert-Eaton myasthenic syndrome as an autoimmune calcium-channelopathy.

Lambert-Eaton myasthenic syndrome (LEMS), often associated with small cell lung carcinoma (SCLC), is a disease of neuromuscular transmission in which antibodies directed against voltage-gated calcium channel (VGCC) in the motor nerve terminal play a crucial role in causing a deficient quantal release of acetylcholine. We focused attention on the P/Q-type VGCC, against which a majority of LEMS patients carry the specific antibody. Since the P/Q-type VGCC expresses in SCLC, the motor nerve terminal and SCLC may share a common VGCC antigen. In search for antigenic sites at the molecular level, We employed peptides or recombinant protein corresponding to the S5-S6 linker of each of four domains forming the alpha 1A subunit and tested their antigenicity. As the result, we specified the domain II, III and IV as immunodominant sites by the induction of an immune-mediated animal model of LEMS and the assay for antibodies in LEMS patients. Also, by use of peptides or recombinant protein corresponding to the synaptotagmin I, we found that in this VGCC-associated protein, the segment which exposes extracellularly during exocytosis can be antigenic for LEMS.

Animals↗
PubMed2000

Insect antifeedant flavonoids from Gnaphalium affine D. Don.

The antifeedant flavonoids, 5-hydroxy-3,6,7,8,4'-pentamethoxyflavone (1), 5-hydroxy-3,6,7,8-tetramethoxyflavone (2), 5,6-dihydroxy-3, 7-dimethoxyflavone (3), and 4,4',6'-trihydroxy-2'-methoxychalcone (4), have been isolated from cudweed Gnaphalium affine D. Don (Compositae). Four natural flavonoids showed insect antifeedant activity against the common cutworm (Spodoptera litura F.). These flavonoids were detected in small amounts in the plant by HPLC analysis, but these natural compounds had strong antifeedant activity against the common cutworm. On the other hand, 4 was detected in a large amount in the plant, but this compound had only a slight activity. Therefore, these natural compounds were regarded as one of the plant's defensive systems against phytophagous insects along with the woolly plant surface. As for the structure-activity relationship, it is an advantage for antifeedant activity to have no oxy-substituents on the B-ring of the flavonoid but have an ether linkage such as a pyran in the chemical structure.

Animals↗
PubMed2000

Antimutagens in gaiyou (Artemisia argyi levl. et vant.).

Antimutagens from gaiyou (Artemisia argyi Levl. et Vant., Compositae) were examined. The methanol extract prepared from aerial parts of this plant strongly reduced the mutagenicity of 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), when Salmonella typhimurium TA98 was used in the presence of the rat liver microsomal fraction. The antimutagens were purified chromatographically while monitoring the antimutagenic activity against Trp-P-2 with a modified Ames test employing a plate method. This purification resulted in the isolation of four strong antimutagens, 5,7-dihydroxy-6,3',4'-trimethoxyflavone (eupatilin), 5, 7,4'-trihydroxy-6,3'-dimethoxyflavone (jaceosidin), 5,7, 4'-trihydroxyflavone (apigenin) and 5,7, 4'-trihydroxy-3'-methoxyflavone (chrysoeriol) from the methanol extract. These antimutagenic flavones exhibited strong antimutagenic activity against not only Trp-P-2 but also against other heterocyclic amines, such as 3-amino-1,4-dimethyl-5H-pyrido[4, 3-b]indole (Trp-P-1), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), 2-amino-3, 8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-3-methyl-9H-pyrido[2,3-b]indole (MeA(alpha)C) in S. typhimurium TA98. In contrast, they did not exhibit antimutagenic activity against benzo[a]pyrene (B[a]P), 4-nitroquinoline-1-oxide (4-NQO), 2-aminofluorene (2-AF), 2-nitrofluorene (2-NF) or furylfuramide (AF-2) in S. typhimurium TA98, or B[a]P, 4-NQO, 2-NF, AF-2, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) or sodium azide (SA) in Salmonella typhimurium TA100, whereas they decreased the mutagenicity caused by aflatoxin B(1) (AFB(1)) and 2-aminoanthracene (2-AA) in both of these tester strains. Regarding the structure-activity relationship, the tested flavones had distinct differences in the intensities of their antimutagenic activities according to the differences of their substitution patterns. Namely, the intensity of antimutagenic activities against Trp-P-2 decreased in the order of: 5,7,3',4'-tetrasubstituted flavones (IC(50): <0.1 mmol/plate), 5,7,4'-trisubstituted flavones (IC(50): 0.120-0.260 mmol/plate), 5,6,7,3',4'-pentasubstituted flavones (IC(50): 0.440-0. 772 mmol/plate). The four isolated flavones were also studied regarding their antimutagenic mechanisms with preincubation methods of the modified Ames test and emission spectroscopic analysis. The results suggested that all isolated flavones were desmutagens which directly inactivated Trp-P-2 or inhibited its metabolic activation.

Antimutagenic Agents↗
PubMed2000

Role of loop D of the alpha7 nicotinic acetylcholine receptor in its interaction with the insecticide imidacloprid and related neonicotinoids.

1. The nitroguanidine insecticide imidacloprid along with a second generation of related compounds including nitenpyram, all nicotinic acetylcholine (ACh) receptor ligands, are used increasingly in many countries. Site-directed mutagenesis and heterologous expression in Xenopus laevis oocytes have been deployed to investigate mutants (G189D and G189E) of the chicken alpha7 homomer-forming nicotinic receptor subunit which are predicted to enhance the negative charge at the negative subsite (loop D) of the ACh binding site. 2. Xenopus oocytes expressing wild-type alpha7 nicotinic receptors respond to imidacloprid with rapid inward currents. Imidacloprid and nitenpyram are partial agonists, whereas ACh, (-)-nicotine and (+)-epibatidine are full agonists. 3. Compared to wild-type alpha7, the mutant G189D and G189E receptors are much less sensitive to the insecticides, whereas their sensitivity to (-)-nicotine, ACh and (+)-epibatidine is only slightly reduced. In contrast, G189N and G189Q mutants are sensitive not only to ACh, (-)-nicotine and (+)-epibatidine, but also to the two insecticides. Thus reduction of the insecticide-sensitivity by the mutations G189D and G189E are attributed to an increase in negativity of loop D. Desnitro-imidacloprid (DN-IMI), an imidacloprid derivative lacking the nitro group is a potent agonist on the G189D and G189E mutants suggesting an important role of loop D in nicotinic receptor interactions with the nitro group of nitroguanidine insecticides.

Animals↗
PubMed2000

Dual metabolic pathway of 25-hydroxyvitamin D3 catalyzed by human CYP24.

Human 25-hydroxyvitamin D3 (25(OH)D3) 24-hydroxylase (CYP24) cDNA was expressed in Escherichia coli, and its enzymatic and spectral properties were revealed. The reconstituted system containing the membrane fraction prepared from recombinant E. coli cells, adrenodoxin and adrenodoxin reductase was examined for the metabolism of 25(OH)D3, 1alpha,25(OH)2D3 and their related compounds. Human CYP24 demonstrated a remarkable metabolism consisting of both C-23 and C-24 hydroxylation pathways towards both 25(OH)D3 and 1alpha,25(OH)2D3, whereas rat CYP24 showed almost no C-23 hydroxylation pathway [Sakaki, T. Sawada, N. Nonaka, Y. Ohyama, Y. & Inouye, K. (1999) Eur. J. Biochem. 262, 43-48]. HPLC analysis and mass spectrometric analysis revealed that human CYP24 catalyzed all the steps of the C-23 hydroxylation pathway from 25(OH)D3 via 23S, 25(OH)2D3, 23S,25,26(OH)3D3 and 25(OH)D3-26,23-lactol to 25(OH)D3-26, 23-lactone in addition to the C-24 hydroxylation pathway from 25(OH)D3 via 24R,25(OH)2D3, 24-oxo-25(OH)D3, 24-oxo-23S,25(OH)2D3 to 24,25,26,27-tetranor-23(OH)D3. On 1alpha,25(OH)2D3 metabolism, similar results were observed. These results strongly suggest that the single enzyme human CYP24 is greatly responsible for the metabolism of both 25(OH)D3 and 1alpha,25(OH)2D3. We also succeeded in the coexpression of CYP24, adrenodoxin and NADPH-adrenodoxin reductase in E. coli. Addition of 25(OH)D3 to the recombinant E. coli cell culture yielded most of the metabolites in both the C-23 and C-24 hydroxylation pathways. Thus, the E. coli expression system for human CYP24 appears quite useful in predicting the metabolism of vitamin D analogs used as drugs.

Adrenodoxin↗
PubMed2000

Antibodies to calcium channel and synaptotagmin in Lambert-Eaton myasthenic syndrome.

In the Lambert-Eaton myasthenic syndrome (LEMS), an autoimmune disease that is often associated with lung cancer and characterized by reduced quantal release of acetylcholine from the motor nerve terminal, our studies to search for the target of LEMS antibodies have brought the voltage-gated calcium channel (VGCC) into relief. Among multiple types of VGCCs, the P/Q-type was highly recognized by LEMS antibodies. Using synthetic peptides or recombinant proteins as antigens, the study specified the S5-S6 linker regions in 3 of 4 domains as immunodominant sites in the molecular structure of P/Q-type VGCC alpha1 subunit. Synaptotagmin, one of the functionally VGCC-associated synaptic proteins, was also found to be an immunogen in the pathogenesis of LEMS.

Autoantibodies↗
PubMed2000

An approach to identify new genes in autoimmune diseases: lessons from rheumatoid arthritis.

We have searched the human genome for genes that predispose to rheumatoid arthritis using fluorescence-based microsatellite marker analysis and affected sib-pair linkage studies. A panel of 41 Japanese families, each with at least two affected siblings, was typed for genome-wide 358 polymorphic microsatellite marker loci. Three principal chromosome regions of linkage, D1S253/214, D8S556 and DX1232, have been assigned, which we call RA1, RA2 and RA3 for rheumatoid arthritis disease loci. We are now assigning the death receptor 3 as a candidate gene for RA1, and the truncated form of Dbl proto-oncogene, which does not contain the 23rd and 24th exons, as disease gene for RA3. Microsatellite marker analyses seem to be promising and new genes are now being identified by reference to sequence tag sites.

Animals↗
PubMed1999

Calcium channel peptide can cause an autoimmune-mediated model of Lambert-Eaton myasthenic syndrome in rats.

The Lambert-Eaton myasthenic syndrome (LEMS) is a disorder of neuromuscular transmission characterized by the reduced quantal release of acetylcholine from the motor nerve terminal, wherein the P/Q-type of voltage-gated calcium channel (VGCC) and is attacked by a majority of LEMS antibodies. Using the molecular structure of the alpha1 subunit (consisting of 4 domains) of the P/Q-type VGCC as a reference, we synthesized the extracellular region (S5-S6 linker) of the domain III, known as the segment which plays an important role in channel functions. Six of the ten Lewis rats immunized with this synthetic peptide conjugated with carrier protein showed moderate weakness (grade 1 in a 3-graded scale, for myasthenic weakness in experimental animals) and a reduction in acetylcholine quantum content of end-plate potentials. Antipeptide antibodies raised in test rats reacted with omega-conotoxin MVIIC-sensitive cerebellar extract (P/Q-type VGCC) and the domain III peptide inhibited the binding of rat antibodies to VGCCs. Our findings suggest the identification of one of the potential epitopes of LEMS antibodies.

Animals↗
PubMed1999

Solitary splenic recurrence of ovarian cancer: case report and review of the literature.

We report a rare case of solitary recurrence of ovarian cancer in the spleen which developed 4 years after initial treatment. Only six cases have been reported in the literature and all were serous carcinoma. Our patient had a splenectomy without any complications but developed a liver metastasis 10 months after splenectomy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

[Premutation in myotonic dystrophy].

Myotonic dystrophy(MyD) is caused by the abnormal expansion of CTG repeats in the 3' untranslated region of a gene encoding a protein kinase. Although some sporadic cases of MyD have been reported, the molecular basis of the intergenerational CTG expansion from asymptomatic parents is not fully understood. To determine the frequency of sporadic cases, we surveyed our clinical records of 40 MyD patients. Four cases with no family history were found, and we analyzed DNA extracted from the peripheral-blood lymphocytes of 2 unrelated patients and their family members. We identified 3 asymptomatic cases, 2 male and 1 female, with premutations which were genetically defined as 40 to 50 abnormal repeats of CTG. The fact that, in our study, the transmitting parents were both male may indicate that paternal transmission could be significant in sporadic MyD cases. We also reviewed the literature of premutation in triplet diseases and discussed the molecular mechanism of marked elongation in triplet repeats during transmission.

Female↗
PubMed1999

[Trends in comprehensive treatment for gynecologic malignancies].

Advances in many areas, including oncology-epidemiology, chemotherapy, diagnosis, surgery, radiology, and clinical research have all had a positive impact on the treatment of gynecologic malignancies, so that today we have achieved an improved quality of life concomitant with increased survival rates in patients. The improvements in therapy for gynecologic malignancies have been in diagnostic procedures, such as tumor markers, molecular biologic methods, and image analysis. Considerable progress has been made in surgical management, from focal excision of primary lesions to minimal debulking surgery after the initial chemotherapy for advanced cancer. Chemotherapy has advanced markedly after the introduction of cisplatin, and various regimens or anticancer drug-analogs of cisplatin, camptotesin, and paclitaxel have been introduced. In recent years, the quality of life of patients with malignancies has been one of the most important factors in treatment. Intensive and combination therapies will be put to greater use for gynecologic malignancy in the future.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Spontaneous thymoma rat as a model for myasthenic weakness caused by anti-ryanodine receptor antibodies.

The mechanism of muscle weakness in myasthenia gravis and its possible relation to antibodies that are directed against the ryanodine receptor (RyR) were studied by the use of the spontaneous thymoma rat (Buffalo/Mna strain). The present study focused on the motor dysfunction as complicated by impaired subcellular machineries and noted particularly in patients with thymus abnormalities. Rats began to develop skeletal muscle weakness soon after birth and worsened progressively. Rats aged 3 months showed a benign thymoma characterized by proliferative lymphocytes; epithelial cells were stained with anti-RyR peptide antibody. The rat serum contained anti-RyR antibodies, but no anti-acetylcholine receptor antibodies. The electrophysiological study in muscle showed a reduction of contractile force without abnormality in synaptic transmission and membrane properties, suggesting a defect in excitation-contraction coupling. Hypothetically, thymic epithelial cells and skeletal muscles share a common RyR antigen, so that anti-RyR antibodies that target the thymic tissue may react with a homologous target in the muscle.

Animals↗