Autoantibodies in myasthenia gravis: demonstration of anti-motor endplate antibody and anti-muscle membrane antibody using membrane immunofluorescence technique

The presence of specific serum antibodies in five myasthenia gravis patients was demonstrated against the motor endplates and muscle membranes of rats by membrane immunofluorescence technique. The immunologic specificity of the antibodies was confirmed. The clinical significance is discussed.</p

A case of systemic lupus erythematosus with idiopathic thrombocytopenic purpura

A 24-year-old woman was presented in whom thrombocytopenic purpura appeared during antiinflammatory drugs therapy for arthralgia. At that time she had a positive LE cell preparation, positive antinuclear factor and false positive serum test for syphilis. Steroid hormon and ACTH therapy were started under the diagnosis of systemic lupus erythematosus. In the 23-rd hospital days, she had a negative LE cell preparation, negative antinuclear factor and negative serum test for syphilis. In the 28-th days after stopping steroid hormon and ACTH therapy, positive LE cell preparation and positive antinuclear factor appeared again

Two cases of bile duct anomalies

We reported two cases of biIe duct anomalies detected by percutaneons transhepatic cholangiography. The first case was a 53-years-old woman who had a long cystic duct running paralleI to, and apparently adhered to a common hepatic duct distally, thus forming one large duct separated by a thin membrane within. Stenosis of the lower bile duct and subsequent dilatation of the proximal part of the duct were also demonstrated. In the second case, 5-years-old girl, the most conspicuous findings include stenosis of the extrahepatic duct with the resultant dilatation of the proximal par t of the common hepatic duct and bilateral hepatic ducts. Distally displaced opening of the common biIe duct to the duodenum and aberrant run of the duodenum were also disrcovered radiographically

Rheumatoid arthritis and Sjögren's syndrome

1. Parotid Sialography Parotid sialograms were investigated in 29 patients with classical or definite RA according to the criteria of the American Rheumatism Association (one of whom had scleroderma), 5 patients with SLE (according to the Dubois's criteria, three were definite, one probable and another possible SLE), 3 patients with other autoimmune diseases (Hashimoto's thyroiditis, colitis ulcerosa and undiagnosed collagen disease), 3 patients with polyarthralgia and 10 patients with nonautoimmune diseases. Sialographic technique was performed by modified Rubin's Method using contrast medium Conray-400. Sialectasis which is pathognomonic of Sjögren's syndrome (SS) alone was observed in 6 patients with RA (20.7%) (3 punctate and 3 globular patterns) and 2 patients with SLE (one punctate and another globular pattern). Retention of the contrast medium in the duct for at least 5 minutes after the injection was observed in patients with RA, one patient with SLE and one patient with colitis ulcerosa. Sial ectasis and retention almost always existed together, and were observed in patients from young to older one. Although dilatation of the Stensen's duct and subalveolar dissection also existed together, they were observed in only older patients. It appeared that the former is the specific findings of SS and the latter is the non-specific findings according to the aging. Dry mouth was complained in 7 sialectasis (87.5%), 3 subalveolar dissection (60.0%), 10 retention (62.5%) and 9 normal sialogram (37.5%). Salivary hyposecretion (less than 10 ml/10min) was observed in 4 sialectasis (50%), one subalveolar dissection (20%), 6 dilatation of the Stensen's duct (37.5%), 5 retention (45.5%) and one normal sialogram (4.2%). These results show that sialectasis and retention are well correlated with salivary hyposecretion, but dry mouth is not so diagnostic in SS. Two patients with SLE had sialectasis were young women and showed normal salivary and lacrimal secretion. These cases may be supported by Heaton's hypothesis that SS is a benign and chronic form of SLE, or thay may be a subclinical state of SS. 2. Schirmer test Sixty seven patients (36RA, 6SLE, 3 other autoimmune diseases, 3 polyarthralgia and 19 non-autoimmune diseases) were examined by Schirmer test. Besides lacrimal hyposecretion was observed in RA and other autoimmune diseases, it began in younger age. These results show that autoimmune diseases have a sicca element in themselves. Compared with the results of sialography, Schirmer test was not correlated with sialectasis and retention. Dry eye was complained in only 4 patients (13.3%) with lacrimal hyposecretion (less than 10mm/5min) and all patients with dry eye had keratoconjunctivitis sicca (KCS). Dry eye is more diagnostic than Schirmer test. 3. Corneal staining by 1% rose bengal solution Twenty five patients with RA or SLE were examned corneal staining (Holm's type A) was observed in 5 patients with RA (20%). Staining of the medial and lateral bulbar conjunctiva (Holm's type B and C) were observed in 6 patients with RA (24%) and one patient with SLE. Nine patients with positive staining (type A, B and C) (75%) showed lacrimal hyposecretion. Dry eye was complained in 4 patients with type A staining (80%), but no patient with type B and C complained dry eye. Dry eye appears to be specific for the diagnosis of SS as sialectasis on the sialogram. 4. Salivary secretion All amount of saliva was collected during ten minutes chewing two pieces of gum. All of 21 patients with non-autoimmune diseases showed more than 10 ml/10min, and slight degree of salivary hyposecretion was observed with aging. Nine patients with RA (25.7%) showed salivary hyposecretion (less than 10ml/10min), besides it began in younger age. It was also observed in patients with other autoimmune diseases. Only 36.4% patients with salivary hyposecretion showed sialectasis on the sialogram. It can be supposed that patients with sialectasis and good salivary secretion are subclinical states of SS, and that this state is depends on the compensative function of the glands. Therefore, it is impossible to suppose the salivary dysfunction from the complaints of patients alone. It is required that saliva must be analysed not only quantitativly but also qualitativly (such as RA factor, complement and lysozome). Dry mouth was not only complained in 9 patients who showed salivary hyposecretion (81.8%). but in 10 patients showed normal secretion (50%). Dry mouth appears to be less specific for the diagnosis of SS than dry eye. 5. Diagnosis of SS Vanslow's criteria of SS was modified as follows. (1) Major : ① Sialectasis or salivary gland enlargement ② Positive corneal staining (type A) ③ Classical or definite RA (according to the criteria of the ARA) (2) Minor : ① Arthritis ② History ot salivary gland swelling ③ Dry mouth or salivary hyposecretion (less than 10ml/10min) ④ Dry eye or positive Schirmer test (less than 10mm/5min). Three major was diagnosed as definite, 2 major as probable and one major with one or more minor as possible SS. Of 35 patients with RA, definite (8.6%), probable (17.1%) and possible SS (54.3%) were obserevd. Two of SLE (33.3%) were possible SS. One patients with undiagnosed collagen disease was possible SS. Clinically, definite and probable SS may be diagnosed as Sjögren's syndrome. Two possible SS with SLE may be supporsed as subclinical states of SS who do not yet exhibite full criteria. Compared with the clinical and laboratory findings of these definite, probable and possible SS with RA, it was supporsed that positive antinuclear factor or positive LE cells in RA patients almost always represents SS, drug allergy, especially to gold therapy may be a manifestation of SS. Hypergammaglobulinemia, extreme elevation of erythrocyte sedimentation rate, struma, lymphnode enlargement in RA patients must be suspected of SS. Although one possible SS with SLE and one probable SS with RA showed positive ANF (peripheral pattern), it is impossible to differentiate SS from SLE by ANF alone. Because Suzuki et al. reported that 15.4% of SS had showed positive ANF (peripheral pattern). Examinations of salivary glands including sialography must be performed in patients with SLE in the future. To detect a subclinical SS, sialography and corneal staining must be performed even in patients with no sicca symptom, because of the compensatory functions of salivary and lacrimal glands

Antibody-dependent cell-mediated cytotoxicity (ADCC) of human peripheral blood leukocytes using sheep red blood cells as target cells Part II. ADCC and erythrophagocytosis of peripheral leukocytes in patients with Sjogren's syndrome or rheumatoid arthritis

Antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent erythrophagocytosis (ADEP) of peripheral blood leukocytes in patients with Sjogren's syndrome (SjS) or rheumatoid arthritis (RA) were investigated using (51)Cr-labelled sheep red blood cells as target cells. The Lymphocytes (phagocyte depleted fraction, PDF) in healthy controls showed higher ADCC activities (58.6±9.9%) than the phagocyte-contaminated crude lymphocyte fraction (CLF) (49.1±10.9%). There was no statistically significant difference between the ADCC activities of PDF in patients with SjS (55.9±13.5%) or RA (58.8±9.6%) and those in healthy controls, although decreased ADCC activity was observed in some patients with SjS. ADCC activities of CLF in patients with SjS (61.2±14.3%) or RA (59.3±6.9%) were significantly higher than those of CLF in healthy controls. Decreased ADEP activity of monocytes in CLF was demonstrated in patients with SjS (17.9±9.4%) compared with healthy controls (37.2±10.6%), and increased ADCC activity of CLF in patients with SjS was dependent on decreased ADEP activity of contaminating monocytes. Decreased ADEP activity of monocytes in patients with RA was also suggested by these results. It was speculated that the decreased Fc-receptor function of peripheral blood monocytes, demonstrated in these patients, had originated from aberrant cell-mediated immunity in these diseases, since these Fe-receptor functions in patients with SjS did not correeate with the following conditions: associated diseases, erythrocyte sedimentation rate, titer of serum rheumatoid factor, lymphocyte count of peripheral blood, or treatment with anti-inflammatory drugs including prednisolone

Safe and Effective Delivery of Small Interfering RNA with Polymer- and Liposomes-Based Complexes

We developed binary and ternary complexes based on polymers and liposomes for safe and effective delivery of small interfering RNA (siRNA). Anti-luciferase siRNA was used as a model of nucleic acid medicine. The binary complexes of siRNA were prepared with cationic polymers and cationic liposomes such as polyethylenimine (PEI), polyamidoamine (PAMAM) dendrimer, poly-L-arginine (PLA), trimethyl[2,3-(dioleoxy)-propyl]ammonium chloride (DOTMA), and cholesteryl 3β-N-(dimetylaminnoethyl)carbamate hydrochloride (DC-Chol). The ternary complexes were constructed by the addition of γ-polyglutamic acid (γ-PGA) to the binary complexes. The complexes were approximately 54-153 nm in particle size. The binary complexes showed a cationic surface charge although an anionic surface charge was observed in the ternary complexes. The polymer-based complexes did not show a silencing effect in the mouse colon carcinoma cell line expressing luciferase regularly (Colon26/Luc cells). The binary complexes based on liposomes and their ternary complexes coated by γ-PGA showed a significant silencing effect. The binary complexes showed significant cytotoxicity although the ternary complexes coated by γ-PGA did not show significant cytotoxicity. The ternary complexes coated by γ-PGA suppressed luciferase activity in the tumor after their direct injection into the tumors of mice bearing Colon26/Luc cells. Thus, we have newly identified safe and efficient ternary complexes of siRNA for clinical use