Biomedical subjects

K Tsuzaka

Publications and source records attributed to K Tsuzaka.

31 records · Page 2Linked to original sources

PubMed1996

Lupus autoantibodies to double-stranded DNA cross-react with ribosomal protein S1.

One cDNA clone (G7) was isolated from a lambda gt11 human liver cDNA library by the reaction with a serum containing anti-dsDNA Abs and was ligated into pGEX-1 lambda T vector. All the 10 SLE sera with anti-dsDNA, 2 samples of human monoclonal anti-dsDNA (33.C9 and 33.H11), and 2 affinity-purified anti-dsDNA Abs recognized the glutathione S-transferase fusion protein expressed by G7 (G7-FP). Ab binding to the recombinant protein expressed by G7 (G7-RP) and to G7-FP was inhibited completely by calf thymus dsDNA. The cDNA was 1314 nucleotides in length and contained an open reading frame encoding 352 amino acids. However, it seems to be a partial length cDNA because the affinity-purified Ab from G7-FP recognized only a 104-kDa protein on Western blot using MOLT4 cell extract. The nucleotide sequence of G7 was homologous (99% identity) to a cDNA encoding human ribosomal protein (r-protein) S1 homologue mRNA. The encoded protein contains repeating residues as a feature of r-proteins S1. Cytoplasmic and nucleolar staining of 33.H11 on indirect immunofluorescence (IF) using HEP 2 cells was inhibited by both G7-RP and calf thymus dsDNA. On ELISA, 33.H11 had a higher affinity for G7-RP than for DNA while 33.C9 had a higher affinity for DNA than for G7-RP and binds nuclei on IF. We conclude that G7 encodes a portion of human r-protein S1 and anti-dsDNA Abs cross-react with this protein.

Amino Acid Sequence↗

PubMed1996

Anti-U5 small nuclear ribonucleoprotein (snRNP) antibodies: a rare anti-U snRNP specificity.

We surveyed for autoantibodies to the U small nuclear ribonucleoproteins (snRNPs) in sera from 1171 patients with various connective tissue diseases by immunoprecipitation assay. We found serum, termed LaJ, which principally recognized the U5 snRNP from one patient with systemic sclerosis-polymyositis overlap syndrome. Anti-LaJ serum immunoprecipitated predominantly U5 snRNA from a 32PO4-labeled HeLa cell extract and at least five U5-specific proteins as well as the Sm core proteins from a [35S]methionine-labeled extract. Anti-LaJ serum immunoprecipitated both U5 snRNA and these five proteins in identical fractions at 15-20S by parallel sucrose gradient, suggesting physical association of these two components. Thus, we concluded that anti-LaJ serum contained antibody specific to the U5 snRNP. Antibodies specific to U5 snRNP were found in a single serum; in contrast, the prevalence of anti-U1 snRNP and anti-Sm antibody was considerably higher. Thus, the specific proteins of the U5 snRNP are rare targets for autoantibodies in patients with connective tissue disease.

Antibodies, Antinuclear↗

PubMed1996

Autoantibodies to double-stranded (ds)DNA immunoprecipitate 18S ribosomal RNA by virtue of their interaction with ribosomal protein S1 and suppress in vitro protein synthesis.

We report that four systemic lupus erythematosus (SLE) patient sera containing anti-dsDNA antibodies, three affinity-purified anti-dsDNA IgG, and a human anti-dsDNA MoAb (33.H11) immunoprecipitate 18S ribosomal RNA from DNase-treated 32P-labelled MOLT4 cell extract. This 18S RNA precipitation was inhibited completely by preincubating 33.H11 with calf thymus dsDNA or the recombinant human ribosomal protein S1, which was reported to cross-react with anti-dsDNA antibodies (J Immunol 1996; 156:1668-75). Whole IgG from three SLE sera with anti-dsDNA antibodies, 33.H11, and three affinity-purified anti-dsDNA IgG inhibited in vitro translation of globin mRNA (percent inhibition was 36-50%). This translation inhibition by anti-dsDNA antibodies was enhanced (67-79%) when the reticulocyte lysate was treated with DNase. Suppression of protein synthesis could be a pathogenic mechanism of anti-dsDNA antibodies, since it has also been shown that anti-dsDNA penetrates living cells (J Immunol 1995; 154:4857-64) in culture.

Antibodies, Antinuclear↗

PubMed1994

Clinical significance of antibodies to native or denatured 60-kd or 52-kd Ro/SS-A proteins in Sjögren's syndrome.

OBJECTIVE: To evaluate the clinical significance of antibodies to native or denatured (anti-n or anti-d) 60- or 52-kd Ro/SS-A proteins (60K or 52K) in Sjögren's syndrome (SS). METHODS: The presence of antibodies to denatured and native Ro/SS-A proteins was determined by immunoblotting and immunoprecipitation, respectively. Salivary gland dysfunction was evaluated by salivary function scintigraphy. RESULTS: The incidence of anti-d-60K without anti-d-52K was lower among patients with systemic lupus erythematosus with SS (SLE/SS) and among those with primary SS, compared with patients who had SLE without SS, whereas anti-d-52K without anti-d-60K was more common in SLE/SS patients and primary SS patients than in SLE patients without SS. All of the patients with anti-Ro/SS-A had anti-n-60K. Serologic abnormalities and salivary gland dysfunction were associated with anti-n-60K in SS, whereas Hashimoto's thyroiditis in SS was related to anti-d-60K. Anti-d-52K was not associated with any extraglandular or glandular symptoms in SS. CONCLUSION: The data indicate that anti-n-60K, which appears to recognize conformational epitopes, is associated with clinical features of SS characterized by glandular dysfunction.

Autoantibodies↗

PubMed1994

Lupus autoantibodies to native DNA cross-react with the A and D SnRNP polypeptides.

Antibodies to native DNA (nDNA) in sera from patients with systemic lupus erythematosus have been found to frequently correlate with antibodies to the A and D SnRNP proteins measured in Western blot assays. 40 of 54 SLE (74.1%) sera with anti-nDNA bound to A and D proteins, while 9 of 113 sera (8%) without anti-nDNA bound the A and D proteins, P < 10(-8) by Fisher's exact test. Antibodies to nDNA correlated closely with anti-A and anti-D in seven of eight patients followed sequentially, r = 0.7865. Nine human polyclonal anti-nDNA populations were isolated from DNA cellulose columns. Seven reacted equally with A and D, and two reacted predominantly with D. Two of three murine monoclonal anti-DNA antibodies isolated from NZB/NZW F1 hybrid mice bound A and D equally in Western blot with a titer > 1/40,000. These reactions were directed to the unfolded A and D proteins measurable in Western blot since these monoclonals (and several of the human anti-nDNA populations) failed to react with native U1RNP in ELISA or in RNA immunoprecipitation experiments. These newly recognized cross reactions of anti-nDNA may amplify the immune response to DNA and be part of the original immunogenic drive.

Animals↗

PubMed1993

Relationship between autoantibodies and clinical parameters in Sjögren's syndrome.

Glandular function as estimated by salivary function scintigraphy and extraglandular manifestations were compared among 174 Sjögren's syndrome (SS) patients according to their anti-Ro/SSA, anti-La/SSB, and anti-U1RNP autoantibody status, to clarify the relationship between these autoantibodies and clinical parameters in SS. These antibodies were detected by RNA-immunoprecipitation. Anti-La/SSB or only anti-Ro/SSA antibody was common in 84 primary SS (P-SS) patients, whereas the frequency of only anti-U1RNP was high in 90 secondary SS (S-SS) patients, especially in those with systemic lupus erythematosus (SLE). Antibody-negativity was common in SS with rheumatoid arthritis and was also found in 33% of P-SS. In P-SS, salivary gland dysfunction and parotid swelling were severe in patients who had serological abnormalities with anti-Ro/SSA and with or without anti-La/SSB. They were mild in antibody-negative patients who had mild extraglandular symptoms and in patients with only anti-U1RNP antibody who had Raynaud's phenomenon, pulmonary fibrosis, and later disease onset. P-SS patients positive for both anti-Ro/SSA and anti-U1RNP had SLE-like features. SS could be classified clinically according to these autoantibodies.

Autoantibodies↗

PubMed1993

Pulmonary pseudolymphoma presented with a mass lesion in a patient with primary Sjögren's syndrome: beneficial effect of intermittent intravenous cyclophosphamide.

A 61-year-old woman with primary Sjögren's syndrome (SS) presented with fever, dry cough, dyspnea on exertion, and a mass lesion with reticular shadowing at both bases on her chest X-ray. Pulmonary pseudolymphoma was diagnosed by transbronchial lung biopsy which revealed infiltration of T cell-like slightly atypical lymphoid cells. After three infusions of cyclophosphamide (750 mg every 4 weeks) combined with prednisolone, the pulmonary mass lesion was diminished and her symptoms improved. Evaluation of the 12 reported cases of pulmonary pseudolymphoma with SS that presented with mass lesions showed an increase in IgM level, frequent pulmonary fibrosis, precedence of SS, and better prognosis with immunosuppressants in those patients.

Biopsy↗

PubMed1993

Nonprecipitating IgG or IgM anti-Sm antibody: clinical significance and changes in immunoglobulin class.

OBJECTIVE: To estimate the clinical significance of IgG or IgM nonprecipitating anti-Sm antibodies and their immunoglobulin (Ig) class switch. METHODS: Ninety-one sera which were positive for anti-nRNP antibodies by double immunodiffusion (DID) were obtained from patients with various rheumatic diseases. Anti-Sm antibody was detected by RNA-immunoprecipitation (RNA-IP). IgG or IgM anti-Sm Ig class was measured by enzyme linked immunosorbent assay using affinity purified D polypeptide from HeLa cells. One hundred sixteen clinical manifestations were compared among these groups of patients. RESULTS: By RNA-IP and DID, 91 were divided into 43 with nonprecipitating anti-Sm which were not detected by DID but by RNA-IP, 17 no anti-Sm, and 31 precipitating anti-Sm sera. In 43 patients with nonprecipitating anti-Sm, renal involvement was more common than in no anti-Sm patients. Besides, systemic lupus erythematosus (SLE)-type manifestations were less common than in precipitating anti-Sm patients. In these 43 patients, IgM anti-Sm class was common (13/43). Decrease in the ratio of IgM to IgG anti-Sm antibody was observed in proportion to the years of observation in these patients. IgM anti-Sm predominated in these patients with mixed connective tissue disease (MCTD)-type manifestations while IgG anti-Sm did in those with SLE-type features. CONCLUSIONS: Patients with nonprecipitating anti-Sm who have IgM anti-Sm at early stages of disease are more likely to have MCTD-type manifestations and later may shift to SLE-type features. These may reflect the anti-Sm Ig class switches from IgM to IgG.

Antibodies↗

PubMed1993

[A case of primary intracranial malignant lymphoma presenting opsoclonus-polymyoclonia syndrome].

A 46-year-old woman was doing well until December 1989, when she noted vertigo and difficulty in walking. She was admitted to our department on February, 7, 1990. General physical examination was unremarkable. Neurological examination revealed opsoclonus, limbs and truncal ataxia, and myoclonus over the facial muscle, neck, and all the extremities, suggestive of opsoclonus-polymyoclonia syndrome. Other neurological finding was not apparent. T2 weighted MRI (Siemens 1.5 Tesla) showed abnormal high intensity area without mass effect at the dentate nucleus of left cerebellum. She was treated with 60 mg of oral prednisolone, followed by gradual improvement of her neurological signs and abnormal MRI findings. However, in May, she gradually developed right hemiparesis, consciousness disturbance and pseudobulbar palsy. MRI showed multiple abnormal intensity area at left frontal lobe, right basal ganglia, and right cerebellar hemisphere. Open brain biopsy from the left frontal lesion revealed malignant lymphoma (diffuse large cell type, B cell type). She was treated by radiation therapy at the dose of 50 Gy (whole brain 40 Gy, local 10 Gy) with subsequent disappearance of opsoclonus, myoclonus, and ataxia. To our knowledge, this is the first case of primary intracranial malignant lymphoma presenting opsoclonus-polymoclonia syndrome.

Brain Neoplasms↗

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

[A case of multiple sclerosis with syrinx formation demonstrated on MRI].

A 26-year-old woman developed two separate episodes of myelopathy mainly presenting paraparesis. Neurologic examination disclosed flaccid paraparesis associated with slight spasticity of the right arm. Deep tendon reflexes were generally hyperactive with positive bilateral Babinski and Chaddock reflexes. Arm pronation sign and Barré leg signs were bilaterally positive. Sensory disturbance below T6, and diminished vibration and position sense in both legs were seen. Urinary and fecal disturbances were also present. She could walk, but her gait was unsteady. Brain MRI showed abnormal high signal intensity areas on T2-weighted image at the left fronto-parietal lobe and right temporo-parietal lobe. Spinal MRI disclosed a cavity formation which was delineated low signal intensity on T1-weighted image through T4 to T8 and high signal intensity on T2-weighted image through T3 to T10. From these clinical manifestations and radiological findings, she was able to be diagnosed to have definite MS. The coexistence of syrinx formation in MS has rarely been reported, and only 5 cases including our case were found. These cases are characterized by the central localization of syrinx, and fair prognosis in their neurological features.

Adult↗

PubMed1991

[A case of epidural lipomatosis presenting spinal ataxia].

A 41-year-old man was doing well until July 1989, when he noted numbness over soles, followed 4 months later by difficulty in walking. These symptoms were progressively getting worse, and he was admitted to our department on June 12, 1990. General physical examination was unremarkable. Neurologically cranial nerves were intact except old right, traumatic strabismus. Muscle tone and deep tendon reflexes were normal throughout, but bilateral Babinski and Chaddock reflexes were present. Mild weakness of lower extremities were found on muscle testing (4/5). In sensory system, superficial sensory disturbance below T10 was seen, and markedly diminished vibration and position senses of lower extremities were noted. Cerebellar test was intact, although unsteadiness was found on heel-shin test. Romberg sign was definitely positive. His gait was wide-based and ataxic. Laboratory data showed no abnormalities in CBC, chemistry, urinalysis, serological tests and endocrinological examinations. Spinal MRI (Siemens 1.5 Tesla) showed abnormal deposition of epidural fatty tissues compressing spinal cord with flattening of cord from T4 to T8. Spinal ataxia as compressive myelopathy due to epidural lipomatosis was considered and he underwent laminectomy from T4 to T8 with improvement in walking. Epidural lipomatosis is an unusual cause of spinal cord compression, presenting compressive myelopathy, radiculopathy, cauda equina syndrome, intermittent claudication, or back pain. Most of cases were associated with long-term administration of adrenocortical steroid hormone, or underlying diseases, except only 3 cases including ours. This is the first case of spinal epidural lipomatosis presenting progressive gait disturbance due to spinal ataxia.

Adult↗