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Biomedical subjects

S Kawanami

Publications and source records attributed to S Kawanami.

At least 19 recordsLinked to original sources

[A case of sarcoidosis with cranial mononeuritis multiplex and peripheral polyneuropathy].

A 67-year-old woman with sarcoidosis, cranial mononeuritis multiplex and peripheral neuropathy was reported. The initial presentation of her sarcoidosis was a subcutaneous nodule of left knee joint on June, 1990. The number of subcutaneous nodules increased. Sarcoidosis was diagnosed by biopsy of the subcutaneous nodule. Paresthesia of the face and limbs appeared from November, 1991 and one month later, left abducens palsy and hearing disturbances were added. Alternate day therapy of 20mg prednisolone was effective in improvement of symptoms. The case of sarcoidosis with cranial mononeuritis multiplex and peripheral polyneuropathy was rarely found in 6 to 25% of patients with sarcoid neuropathy in the previous reports. Angiotensin-converting enzyme (ACE) in cerebro-spinal fluid not only raised on exacerbation also lowered with improvement of symptoms after steroid therapy. The ACE, which had a selective activity in the central nervous system, seemed to contribute to the index of treatment for sarcoidosis.

Aged

Immunoadsorption therapy for myasthenia gravis.

The results of a multicentre trial were analysed to evaluate the efficacy of immunoadsorption therapy for severe generalised myasthenia gravis. Twenty patients with myasthenia gravis who were concurrently receiving high dose prednisolone and azathioprine therapy were treated with an affinity-type adsorbent, using tryptophan-linked polyvinyl alcohol gel (IM-TR), according to a standardised treatment protocol. The 20 patients received five adsorption treatments within a period of 10 days. In 11, pronounced improvement of myasthenic weakness was seen and long-term remission was maintained. The treatment was especially effective in patients with thymic hyperplasia. Circulating acetylcholine receptor (AChR) antibodies were reduced by about 60% by treating one plasma volume. There was no difference in the rate of removal of the AChR antibodies between patients with thymic hyperplasia and patients with thymoma. No serious complications occurred during 100 procedures. It was concluded that the immunoadsorption therapy with IM-TR is useful in controlling symptoms in patients with severe myasthenia gravis who are otherwise unresponsive.

Adolescent

Experimental autoimmune myasthenia gravis induced by thymic acetylcholine receptor-like protein.

The trigger mechanism of autoimmunity in myasthenia gravis (MG) has yet to be elucidated. To determine the function of the thymus in the pathogenesis of MG, we tried to produce chronic experimental autoimmune myasthenia gravis (EAMG) using nicotinic acetylcholine receptor-like protein (n-AChR-LP) isolated from the fetal calf thymus (FCT) by affinity chromatography with Sepharose-4B bound cobrotoxin. Lewis rats were inoculated with n-AChR-LP emulsified in Freund's complete adjuvant and later received two booster immunizations. The immunized rats developed generalized hypotonia at seven to ten days and then recovered spontaneously within two weeks. In the fourth week, flaccid paresis with either a hunched posture or waddling gait appeared in half of the rats, these symptoms improved transiently after treatment with neostigmine. At this time, evoked EMG showed decremental responses after curare sensitization, while anti-n-AChR-LP antibody, measured by enzyme-linked immunosorbent assay (ELISA), increased significantly. These findings therefore suggest that the n-AChR-LP from the thymus includes antigens to induce EAMG.

Animals

[Evaluation of results following thymectomy in myasthenia gravis].

Sixty-nine patients with generalized myasthenia gravis underwent thymectomy consecutively between 1980 and 1991 and were evaluated 1 month to 120 months after operation. Extended thymectomy was performed in 43 patients and other procedures in 26. The effect of thymectomy were as follows: 14.5% of the patients achieved complete remission (no symptoms, no medication), 73.9% showed improvement; in total 88.4% had palliation. The long-term changes of the remission rate at one and five years after operation were 11.5% and 19.2%, and showed a delayed remission. The long-term changes of the improvement and palliation rate were 55.7% and 67.2% at one year, 69.2% and 88.5% at five years after operation. There was significant difference in remission rate according to age at the time of operation and age of onset, but the response did not depend on sex, presence or absence of thymoma, preoperative duration of illness, Osserman's type and operative procedure.

Adolescent

Nonneoplastic and nonhyperplastic thymus in myasthenia gravis. An immunohistochemical study with double immunoenzymatic labeling of basement membrane and cellular components.

Histologically normal thymus (type A) in patients with myasthenia gravis (MG) was immunohistochemically compared with hyperplastic MG thymus (type B) and normal non-MG thymus. In formalin-fixed, paraffin-embedded sections of ten type A, ten type B, and eight non-MG cases, the thymic epithelium and other cellular components were stained in conjunction with the basement membrane by a double immunoenzymatic method. This technique demonstrated a moderate architectural disturbance in type A thymus, with distended perivascular space (PVS), elongated medullary epithelium, and disrupted basement membrane. These changes were more prominent in type B thymus but were minimal to lacking in non-MG thymus. Compared with those in non-MG thymus, the myoid cells in MG thymuses of both types tended to cluster around the Hassall's corpuscles, with a slight decrease in number in type B but not in type A. B-lymphocytes were present in type B, type A, and non-MG thymuses in that order of abundance; the cells were confined to the medullary parenchyma in the non-MG group but were numerous both in the PVS and medulla in the MG groups. T-lymphocytes were increased in the expanded PVS of type A and B MG thymuses. The number of interdigitating reticulum cells was similar in the three groups, but the cellular distribution was more dispersed in MG thymuses of both types. These findings, although previously described in type B thymus, have not been well recognized in type A thymus. They support the view that a common abnormality (presumably chronic thymitis), differing in degree only, underlies MG thymuses regardless of the presence of follicular hyperplasia.

Adolescent

Isolation and characterization of nicotinic acetylcholine receptor-like protein from fetal calf thymus.

A nicotinic acetylcholine receptor-like protein (AChR-LP) was isolated from fetal calf thymus by affinity chromatography using cobrotoxin-Sepharose after alkaline extraction and solubilization with Triton X-100. The AChR-LP had a specificity of 1.61 +/- 1.12 nmol of alpha-bungarotoxin binding sites per mg of protein. The isoelectric point, sedimentation coefficient and amino acid composition of the purified AChR-LP were very similar to those of muscle and electric organ AChRs. Upon SDS-polyacrylamide gel electrophoresis purified thymus AChR-LP preparations contained up to 6 polypeptide bands of molecular weights of 40,000, 43,000, 51,000, 56,000, 58,000, and 66,000, respectively. The peptides of 40,000, 51,000, 56,000, and 66,000 dalton cross-reacted with the four subunits of Torpedo californica and fetal calf muscle AChR.

Amino Acids

Acetylcholine-receptor-like protein from human thymoma associated with myasthenia gravis.

Cobrotoxin-binding protein was isolated by affinity chromatography from human thymoma which had been surgically removed from patients with myasthenia gravis. The protein was composed of polypeptides with a molecular mass of 40, 51, 65, and 74 kilodaltons as determined by polyacrylamide gel electrophoresis in the presence of sodium dodecylsulphate. Isoelectric focusing of the protein gave pI values of 5.2-5.6 and 11. This is the first report of the isolation of the protein from human thymoma. These findings suggest that the cobrotoxin-binding protein from human thymoma patients with myasthenia gravis has subunits similar to those of fish electric organs or mammalian muscles.

Adult

Purification of acetylcholine receptor-like protein from fetal calf thymus.

A cobrotoxin binding protein from the fetal calf thymus was isolated by affinity chromatography after solubilization with sodium cholate. The specific activity as a nicotinic acetylcholine receptor (AChR) was determined by assessing the binding to [3H]-alpha-bungarotoxin (BuTx), using the high-pressure liquid chromatography. An AChR-like protein was detected in the amount of 1.39-2.14 nmol per g protein. The first peak of 420k-protein from gel filtration of the eluate of affinity chromatography on a Sephacryl column showed one major polypeptide band with an Mr of 40k, by polyacrylamide gel electrophoresis in sodium dodecylsulfate, two major protein bands with pI 5.4-5.6 and 9.2 by isoelectric focusing, and reacted with sera from patients with myasthenia gravis.

Animals

Enzyme-linked immunosorbent assay for antibody against the nicotinic acetylcholine receptor in human myasthenia gravis.

Antibody against acetylcholine receptor (AChR) of human skeletal muscle was measured using enzyme-linked immunosorbent assay and found in 23 (74%) of 31 Japanese patients with generalized myasthenia gravis. In 15 patients with generalized myasthenia gravis who had not undergone thymectomy and who were not receiving adrenocorticosteroids, the antibody was found in 13 (87%). Antibody was also found in 13 (54%) of 24 patients with myasthenia gravis against AChR fractions obtained from fetal calf thymus. Based on the subunit structures of the AChR protein, the double precipitation assay using iodine 125-alpha-bungarotoxin is also capable of detecting antibody against the toxin binding site, by cross reactivity. This is among the first reports of experiments in which enzyme-linked immunosorbent assay was used to measure the antibodies in human myasthenia gravis and provides evidence of anti-AChR antibody against antigens from fetal calf thymus.

Autoantibodies

Isolation of acetylcholine receptor-like protein from fetal calf thymus.

Cobrotoxin-binding protein from fetal calf thymus was isolated by affinity chromatography after solubilization with Triton X-100 or sodium cholate. Its specificity as a nicotinic acetylcholine receptor (AChR) was determined by assessing the binding to radiolabeled alpha-bungarotoxin (BuTx) and to serum containing antibody against AChR obtained from a patient with myasthenia gravis (MG). AChR-like protein was detected in the amount of 0.41 -2.04 X 10(-9) mol alpha-BuTx binding sites per g protein. Polyacrylamide gel electrophoresis in sodium dedecylsulfate (SDS) revealed polypeptide bands with molecular weights of 40,000, 46,000, 55,000, 70,000, 35,000, and 26,000 daltons. As this protein may play an important role in immunopathological changes in MG, related studies are underway.

Animals

Segmental demyelination and remyelination in lumbar spinal roots of patients dying with diabetes mellitus.

Morphometric evaluations of histopathological changes in postmortem materials from three patients with diabetes mellitus with neuropathy, nephropathy, and retinopathy were made on the sural nerve, lumbar spinal roots, lumbar dorsal root ganglion (2 cases), and fasciculus gracilis. In all three patients there was a marked decrease in densities of both the large and the small myelinated fibers in the sural nerves. In the lumbar spinal roots, segmental demyelination and remyelination with or without decrease in the number of myelinated fibers per root was the main finding in both dorsal and ventral roots, being more common in the dorsal roots. At the third cervical segment of the fasciculus gracilis, the myelinated fiber density was slightly decreased in one patient and moderately decreased in the other two. The number of cell bodies of the fifth dorsal root ganglion was within normal limits in the two patients where this was examined, although the median diameters approximated the lower limit found in controls. The potential presence of segmental demyelination and remyelination in dorsal and ventral spinal roots should be considered especially when assessing electromyographic changes and nerve conduction in diabetic patients.

Adult

Role of thymectomy in the surgical treatment of myasthenia gravis.

Of the 26 patients with myasthenia gravis undergone thymectomy, 11 cases had either benign or malignant thymoma as judged not only by hitological examination but also by their clinical and operative findings. Age of initial onset ranged from 13 to 64 years old. Fifteen out of 26 (58 per cent) benefited from thymectomy. Duration of the symptom from the onset to the operation and the presence or absence of the thymoma are not related to their outcome. Benign or malignant nature of thymoma should not be determined by histological examination alone but by combined evaluation of clinical and operative findings. Serial studies of serum immunoglobulin levels before and after thymectomy suggested that this disorder could be associated with humoral antibody (IgG). HLA typing of the patients with myasthenia gravis did not indicate the presence of any specific antigens.

Adolescent

Lymphocyte function in myasthenia gravis.

Mitogen-induced blastoid transformation of peripheral blood lymphocytes from patients with myasthenia gravis was studied using a microplate culture technique and evaluated with 3H-thymidine incorporation. It was found that both phytohaemagglutinin and pokeweed mitogen responses decreased significantly in patients with myasthenia gravis. In myasthenic crisis, indices of stimulation by phytohaemagglutination became very low. The autologous plasma neither inhibited nor facilitated mitogenic responses of lymphocytes. The decreased mitogen responsiveness of lymphocytes suggests that part of the T lymphocyte function is subnormal in myasthenia.

Adult

T and B lymphocytes in myasthenia gravis.

Peripheral blood lymphocytes from seventeen non-thymectomized and nine thymectomized patients with myasthenia gravis (MG) and thirteen healthy controls were examined for the presence of surface markers characteristic of T and B lymphocytes by rosette formation with sheep red blood cells (SRBC). T cells were identified by their capacity to spontaneously form rosettes with SRBCs. The percentage of B lymphocytes was determined by the erythrocyte antibody complement (EAC) rosette-forming test. The EAC complex was prepared with either whole rabbit anti-SRBC serum or with the IgM fraction of rabbit anti-SRBC serum. The two kind of erythrocyte complement rosette-forming cells (EAC-RFC) are designated erythrocyte-haemolysin-complement RFC (EA(H)C-RFC), and erythrocyte-IgM-complement RFC (EA(M)C-RFC). The percentage of total lymphocytes and T cells was not altered in MG patients. The percentage of 'active' T cells, which have been considered to be more actively involved in cellular immunity, was also similar in MG patients and controls. A significant increase in EA(H)C-RFC occurred in both thymectomized and non-thymectomized MG patients, while in B cells detected by EA(M)C-RFC no alterations were found. The increase in EA(H)C-RFC in lymphocytes from MG patients may be due to an increase in the 19S antibody-forming B lymphocytes or to an increase in T cells which have Fc receptors on their surface.

Adolescent

HLA and Japanese MS.

Determination of HLA-A, -B and -C types in 43 Japanese patients with multiple sclerosis (MS) and of DR type in 25 MS patients was carried out using antisera from the 7th International Histocompatibility Workshop. The results were compared with 46 controls typed simultaneously. Twenty-three patients were also tested for HLA-Dw2. The conclusions were: 1) There were no significantly higher occurrences of HLA-A3, B7, Dw2 or DRw2 in Japanese MS. 2) Japanese MS might nevertheless be associated with the human major histocompatibility complex, because HLA-B40 was significantly less frequent in MS and two anti HLA-DRw sera, 7w008 and 034, reacted positively more often against lymphocytes from MS patients.

Epitopes