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M Akizuki

Publications and source records attributed to M Akizuki.

At least 91 records · Page 5Linked to original sources
PubMed1992

Autoantigenic epitopes of the B polypeptide of Sm small nuclear RNP particles. Identification of regions accessible only within the U1 small nuclear RNP.

OBJECTIVE: To analyze the autoantigenic epitopes of the Sm B polypeptide of the U1 small nuclear RNP (snRNP) using complementary DNA (cDNA) clones. METHODS: Expression of Sm B fusion proteins in lambda phage vectors, immunoblots, immunoprecipitations, and affinity purification of antibodies. RESULTS: Immunoblots using antibodies affinity-purified from B fusion proteins demonstrated that there were cross-reactive epitopes between the B'/B and A polypeptides of the U1 snRNP. Immunoprecipitation assays suggested that there were at least 3 different autoantigenic epitopes on the B polypeptide that could be classified into 2 general groups based upon autoantibody reactivity. The first group of autoantibodies, which bound 2 separate autoantigenic epitopes (BU1-1, BU1-2), participated in immunoprecipitation of the U1 snRNP alone. The second group, which bound the third type of autoantigenic epitope (BSm-1), immunoprecipitated all the abundant Sm snRNPs. CONCLUSION: There is at least 1 region on the B proteins that is accessible to antibodies only within the structure of the U1 snRNP, as well as a region that is accessible on all Sm snRNPs. These data support the notion that the native U1 RNP, perhaps containing B proteins in a different conformation than those found on other Sm snRNPs, may drive the humoral immune response in systemic lupus erythematosus.

Amino Acid Sequence↗
PubMed1992

Recurrent annular erythema associated with anti-SS-B/La antibodies: analysis of the disease-specific epitope.

We have found that anti-SS-B/La antibodies are present in a group of patients with a characteristic recurrent annular erythema, and immunological abnormalities. The presence of a disease-specific epitope for this entity has been examined by comparing immunological reactivity of anti-SS-B/La antibodies between these patients and patients with classical Sjögren's syndrome who have anti-SS-B/La antibodies but do not have this characteristic erythema. In immunoblotting using three different antigen sources, all the sera from both groups exhibited the same reaction patterns. V8 protease mapping showed that the sera could be divided into three groups by the difference in reactivity to two main digested peptide fragments. However, no significant relationship of the reactivity in peptide mapping between the two patient groups was observed. Further studies are necessary to elucidate the role of anti-SS-B/La antibodies in disease pathogenesis in these patients, in particular by more precise peptide mapping using recombinant SS-B/La antigen proteins.

Adult↗
PubMed1992

[A case of Wegener's granulomatosis with necrotizing granuloma limited to intraorbital lesions].

A patient of Wegener's granulomatosis (WG) who developed intraorbital tumor without pulmonary and renal involvement was reported. A 52-year-old male has suffered from visual disturbance and right proptosis. Administration of betamethasone resulted in a temporary relief of his symptoms. However, following the reduction of steroid dosage, severe recurrence of ocular symptom occurred and his right sight was completely lost. On admission to our hospital, there were swollen eyelids and saddle nose. The CT scan demonstrated intraorbital tumors bilaterally associated with chronic sinusitis. The repeated biopsies of nasal mucosal lesions disclosed presence of a giant cell granuloma with necrotizing vasculitis. A diagnosis of WG had been made, so intermittent high-dose intravenous cyclophosphamide therapy were initiated. The size of the bilateral intraorbital tumors reduced with continuous cyclophosphamide therapy. At the last observation during 22 months after the initiation of cytotoxic therapy, there was no evidence of clinical and radiological recurrence. Three cases of WG with intracranial tumors in our hospital showed multiple cranial nerve palsy and poor response to corticosteroid therapy. The "limited form" without renal involvement has been known as a subset of WG with a relatively good prognosis. This report suggest the existence of further limited form with intracranial granuloma as a cardinal presentation of WG. Although the extent of granulomatous lesions are limited and progression is slow, the treatment by corticosteroid alone is not sufficient and as the systems form of WG, combined therapy with cyclophosphamide appeared to be indicated.

Betamethasone↗
PubMed1992

[Spontaneous remission of dermatomyositis which developed one month after normal delivery].

A case of dermatomyositis which developed one month after normal delivery and subsided spontaneously was reported. A 29-year-old woman gave birth to a healthy child. One month later, she noticed muscular pain and weakness of the upper extremities. On admission, there were diffuse edema of upper eyelids with heliotrope rash. The reddish skin rashes were observed on the extensor surfaces of the PIP and MP joints of fingers. Erythrocyte sedimentation rate was 29 mm/hr. The lactic dehydrogenase (LDH), SGOT, CK levels were 470 (normal 150 to 320 IU/l), 43 (normal 6 to 25 IU/l) and 317 (normal 21 to 110 IU/l) respectively. Autoantibodies to nuclear and cytoplasmic antigens were negative. Rheumatoid factor and anti-DNA antibody were negative. Thyroid function was normal. An electromyogram (EMG) demonstrated small amplitude short-duration polyphasic motor unit potentials. The muscle biopsy specimen from left upper arm showed degenerating muscle fibers and infiltration of inflammatory cells surrounding blood vessels. The skin biopsy revealed the presence of edema and perivascular infiltration of lymphocytes. Based on these clinical features and results of various diagnostic tests, a diagnosis of dermatomyositis was established. After the admission, muscle strength has improved dramatically and the CK returned to normal level without specific drug therapy. She has since been seen as an out patient, and complete remission lasted for two years up to date. Review of the literature disclosed that 13 cases of PM/DM which developed during pregnancy or postpartum have been reported including the present case. Detailed analysis showed that these patients were characterized by mild muscular diseases, rare occurrence of internal organ involvements and good response to steroid therapy. As our case, a spontaneous remission was also observed. Although the mechanism involved in occurrence of inflammatory myositis associated with pregnancy or delivery are not clarified, these patient indicated a presence of subset of PM/DM which do not require intensive drug therapy.

Adult↗
PubMed1991

Transport of cephalexin to the cerebrospinal fluid directly from the nasal cavity.

The aim of the present study has been to confirm the existence of a transport pathway for a drug (cephalexin) to the cerebrospinal fluid (CSF) directly from the nasal cavity, by comparing the drug's concentrations in CSF after intranasal (i.n.), intravenous (i.v.) and intraduodenal (i.d.) administration. Higher levels of the drug were found in CSF following i.n. administration compared with the i.v. and i.d. routes, even though its plasma concentrations were similar. These findings suggest the existence of a direct transport pathway for cephalexin from the nasal cavity to the CSF. The concentration of drug in CSF at 15 min after i.n. administration was higher than that at 30 min. In contrast, its concentrations in CSF at 15 min after i.v. and i.d. administration were not significantly different from those at 30 min. The results confirm the presence of a direct transport pathway to CSF from the nasal cavity. This pathway may represent a new delivery route to CSF and possibly to brain parenchyma.

Administration, Intranasal↗
PubMed1991

The transport of a drug to the cerebrospinal fluid directly from the nasal cavity: the relation to the lipophilicity of the drug.

The objective of the present study was to clarify the relation between drug transport to the cerebrospinal fluid (CSF) from the nasal cavity and the lipophilicity of the drug using hydrophilic sulfonamides as model drugs. The nasal cavity of the rat was perfused in a single pass system and the concentrations of sulfonamides in plasma and CSF were measured. The drug concentrations in CSF and plasma after nasal perfusion were compared with those after intravenous (i.v.) administration. The drug concentrations in the CSF were remarkably high after nasal perfusion in comparison with those after i.v. administration, though the time course of the plasma concentration was not much different from that after i.v. administration. These results suggested the existence of a direct transport pathway of the sulfonamides from the nose to the CSF. In addition, the drug concentrations in the CSF increased with increasing the lipophilicity of the drugs (the partition coefficient (Pc) of the drugs between isoamyl alcohol and pH 7.4 phosphate buffer). A significant correlation was observed between the drug concentrations in CSF and Pc. In conclusion, the direct transport pathway of the sulfonamides from the nose to the CSF was confirmed and, with regard to drugs with comparatively low lipophilicity, the degree of the transport depended on its Pc.

Animals↗
PubMed1991

A novel autoantibody reactive with a 48 kDa tRNA associated protein in patients with scleroderma.

We identify 4 patients with progressive systemic sclerosis (PSS) possessing a previously undescribed serum anti-tRNA Ab (anti-Wa antibody). These sera yielded identical precipitin lines under double immunodiffusion using calf thymus extract and supernatant of pig spleen homogenate as antigen sources. Furthermore, all 4 sera were found to react with a 48 kDa protein using immunoblotting. This protein was subsequently found to be associated with tRNA when immunoprecipitation was conducted. In a survey of autoimmune patients' sera, anti-Wa Ab was observed in 3% (4 of 130) of patients with PSS, but not in other systemic rheumatic diseases. None of the 4 patients with PSS with anti-Wa Ab had myositis except that one patient complained of mild myalgia.

Aged↗
PubMed1991

[Amelioration of secondary hypertrophic osteoarthropathy following tumor resection in a patient with primary lung cancer].

A 41 year-old female presented with swelling of lower extremities and polyarthralgia involving both knee joints. Physical examination revealed presence of finger clubbing, tenderness and pain-on-motion in knee and foot joints. A chest X-ray film showed a solitary tumor in the right mid-lung field. There were subperiosteal new bone formation and radioisotope accumulation in the legs bilaterally. The clubbing, periostitis and arthritis confirmed a diagnosis of hypertrophic osteoarthropathy. Adenocarcinoma was the biopsy diagnosis of the lung tumor. The characteristic features of hypertrophic osteoarthropathy resolved after surgical resection of the pulmonary lesion followed by chemotherapy. This case demonstrates a typical example of identification of a treatable malignant condition by rheumatic symptoms.

Adenocarcinoma↗
PubMed1990

Isolation and characterization of cDNA encoding the 80-kDa subunit protein of the human autoantigen Ku (p70/p80) recognized by autoantibodies from patients with scleroderma-polymyositis overlap syndrome.

Anti-Ku (p70/p80) autoantibodies in patients with scleroderma-polymyositis overlap syndrome recognize a 70-kDa/80-kDa protein heterodimer which binds to terminal regions of double-stranded DNA. In the present study, we isolated full-length cDNAs that encode the 80-kDa Ku subunit. Initial screening of a human spleen cDNA library with anti-Ku antibodies yielded a cDNA of 1.0 kilobase (kb) (termed K71) encoding a portion of the 80-kDa Ku polypeptide (identification based on immunological criteria). In RNA blots, this cDNA hybridized with two mRNAs of 3.4 and 2.6 kb. In rescreening of a cDNA library constructed from simian virus 40-transformed human fibroblast mRNA with the K71 cDNA as a hybridization probe, three positive clones were isolated, and that bearing the longest insert (termed Ku80-6) was selected for further characterization. In vitro transcription and translation experiments produced an immunoprecipitable polypeptide which comigrated with the 80-kDa Ku subunit. The Ku80-6 cDNA proved to be 3304 nucleotides in length, with an additional poly(A) tail, closely approximating the size of the larger mRNA. It contains a single long open reading frame encoding 732 amino acids (Mr = 82,713). The putative polypeptide has a high content of acidic amino acids and a region with periodic repeat of leucine in every seventh position which may form the "leucine zipper" structure. In genomic DNA blots, probes derived from the opposite ends of cDNA Ku80-6 hybridized with several nonoverlapping restriction fragments from human leukocyte DNA, indicating that the gene encoding the 80-kDa Ku polypeptide is divided into several exons by intervening sequences.

Amino Acid Sequence↗
PubMed1990

Adult Still's disease: a multicenter survey of Japanese patients.

A comprehensive survey of Japanese patients with adult Still's disease was made by questionnaire which was sent to major institutions with rheumatology units in Japan. Of 146 cases from 32 institutions, 90 were judged to be definitely diagnosed as adult Still's disease. The major clinical features in these 90 patients consisted of high fever, polyarthralgia, rash, increased erythrocyte sedimentation rate, negative autoantibodies, leukocytosis, liver dysfunction, and hyperferritinemia. The incidence of several features showed significant differences between these cases and previous nonJapanese cases.

Adolescent↗
PubMed1989

Molecular cloning of cDNA encoding Sm autoantigen: derivation of a cDNA for a B polypeptide of the U series of small nuclear ribonucleoprotein particles.

The Sm snRNPs play a central role in the processing of pre-mRNA. Anti-Sm antibodies, the diagnostic hallmark of systemic lupus erythematosus, target the B'/B and D polypeptides of these snRNPs. We have used patient autoantibodies to clone a cDNA from a human fibroblast cDNA library that encodes the full length of a polypeptide identical with, or closely related to, polypeptide B. This cDNA is comprised of 1139 bases and contains an open reading frame of 855 nucleotides that is capable of encoding 285 amino acids. The first 223 amino acids at the NH2 terminus exhibit nearly complete homology with polypeptide N, a newly recognized brain- and heart-specific component of Sm snRNPs. The derived amino acid sequence for B differs from that of the N polypeptide primarily by a 50-amino acid insert 12 residues upstream from the homologous COOH termini of these polypeptides. The structural differences in these cDNAs for B and N may regulate tissue-specific alternative splicing mechanisms for mRNA. In addition, these clones make it possible to map in fine detail the most characteristic autoimmune responses of systemic lupus erythematosus.

Amino Acid Sequence↗
PubMed1989

[A case of anti-phospholipid antibody syndrome presenting chorea as an initial manifestation].

A 20 year old female patient with anti-phospholipid antibody syndrome who presented chorea as an initial symptom is described. At the age of 14, she noticed involuntary movements of upper and lower extremities bilaterally. The CT scan revealed the presence of low density areas in the right caudate nucleus and left putamen. The result of the laboratory tests included antibodies to nuclear antigens (positive FANA and anti-DNA), prolonged PT and APTT, biological false positive for syphilis. Her serum contained antibodies to cardiolipin and phosphatidylserine as demonstrated by specific ELISA assay method. The clinical diagnosis of chorea was made and haloperidol was administered with partial symptomatic improvements. The patient reported here is the first well documented case of anti-phospholipid antibody syndrome presenting chorea as an initial manifestation in the Japanese literature.

Adult↗
PubMed1989

[Frequency of anti-centromere antibodies in the anti-mitochondrial antibody positive sera].

Autoantibodies give us useful informations for the understanding of the co-existence of multiple autoimmune diseases in an individual patient. This study was undertaken to clarify the frequency of anti-centromere antibodies in the sera which were positive for anti-mitochondrial antibodies. Serum samples with anti-mitochondrial antibodies were examined on the frozen rat liver section and HEp-2 cells by indirect immunofluorescence. 57 out of 239 anti-mitochondrial antibody positive sera were found to contain specific autoantibodies reactive with centromeric antigens of the HEp-2 chromosomal spreads. The co-existence of anticentromere antibodies with anti-mitochondrial antibodies were significantly more frequent than with other defined autoantibodies. Clinical observation which shows frequent association of CREST syndrome and primary biliary cirrhosis appear to be explained by the frequent occurrence of anti-centromere antibodies and anti-mitochondrial antibodies.

Autoantibodies↗