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The complete nucleotide sequence of RNA-2 from a Japanese isolate IP of broad bean wilt virus (BBWV) was determined. The sequence encodes a single large polyprotein, which contains a putative movement protein and two coat proteins (CPs). The 3'-terminal sequences of RNA-2 were also determined for three other Japanese isolates and two ATCC isolates (PV132 and PV176) of BBWV. The CPs of the four Japanese isolates share 86.8-98.0% amino acid sequences homology with one another and 88.3-96.5% with those reported for the isolate PV131 (BBWV-2). However, they have only 57.9-66.2% homology with those of PV132 and PV176 (BBWV-1).

The alanine-polystyrene dosimeters analysed by electron spin resonance (ESR) spectrometry were manufactured for large-scale use as a routine dosimeter in industrial radiation processing facilities by using an injection moulding method. Injection moulding enables us to achieve mass production of uniform dosimeters at a reduced cost. Their primary characteristics for dosimetry were studied in terms of their gamma-ray dose-response at radiation processing dose levels, precision, and effect of temperature during irradiation at an absorbed dose of 1 kGy. The precision of dose-response in the range 0.1–100 kGy is within ± 2% at a 68% confidence level with and without correction for sample-to-sample mass scattering. The irradiation temperature coefficient for dosimeters irradiated to 1 kGy is estimated to be 0.25%/°C, by normalizing to those irradiated at 25°C in the temperature range from 5 to 45°C. The fading of the radiation-induced ESR signal at doses of 0.1–100 kGy at 25°C and r.h. 40% is

Rice necrosis mosaic virus (RNMV) has physico-chemical and biological properties typical of the Bymovirus genus. However, to date no sequence data has been reported for RNMV. In this paper we report the use of a PCR primer, designed from an area of high homology between bymoviruses and related macluraviruses within the NIb gene, which generated a 1.4kb fragment from the 3' terminal region of RNA 1 of RNMV. The sequence data generated from this region confirmed the classification of RNMV as a member of the Bymovirus genus.

The biological and serological properties of two Japanese barley mild mosaic virus (BaMMV) strains (BaMMV-Kal and BaMMV-Nal) and a German BaMMV strain (BaMMV-M) were compared. Mechanical inoculation experiments showed that these three strains differed from one another in their ability to infect specific barley cultivars. BaMMV-Kal and BaMMV-M caused similar symptoms, but BaMMV-Nal clearly differed from them in its symptoms on some barley cultivars. The three BaMMV strains efficiently infected barley plants at 15°C, whereas at 20°C BaMMV-Kal and BaMMV-M also infected many plants but BaMMV-Nal infected only a few. BaMMV-Kal and BaMMV-M were indistinguishable by ELISA, while BaMMV-Nal was distinguished from both. The biological and serological variability reported shows that BaMMV occurs as two distinct strains in Japan.

Orientation effects during electron spin resonance (ESR) measurement are studied on alanine-polymer dosimeters prepared by different molding procedures (press-molding or extrusion), and also according to different shapes (rods with different lengths and thin-films). The variation in ESR signal amplitude was measured by rotating a dosimeter around the vertical mid-axis and at a right angle to the magnetic field in the ESR cavity, at a temperature of 22°C. Orientation effects for rod dosimeters with both molding procedures (press and extrusion), and with different lengths, were negligible. Thin-film dosimeters molded by extrusion show a pronounced orientation effect when the samples are cut into disks and positioned horizontally (parallel to the magnetic field) during readout in the ESR cavity. Orientation effects on the film dosimeters can be eliminated, however, when they are positioned vertically and parallel to the mid-axis of the ESR cavity.

A thin-film dosimeter was prepared by homogeneously mixing ground DL-α-alanine crystalline powder and melted low-density polyethylene and by subsequent extrusion into a long tape with 8 mm width. The basic dosimetric characteristics of the 200-μm thick film dosimeter were studied for 60Co gamma-rays and 2.0-MeV electron beams. Dose responses were measured using a conventional electron spin resonance (ESR) spectrometer as well as a custom-made compact reader. The ESR measurement procedure was improved by the design of a dosimeter holder for high reproducibility, which avoided the orientation effect of samples during ESR readings. The random uncertainty of dose response among 20 irradiated replicate dosimeters is ±1% (1σ) for absorbed doses of 103–105 Gy, with correction being made for the weight differences of the dosimeters. The measurable dose range using the conventional ESR spectrometer is from 0.05 to 100 kGy. The compact reader can also be applied for dose evaluation above 1 kGy, with a precision within 1%, covering the measurable dose ranges of both FWT-60 radiochromic film and cellulose-triacetate film dosimeters. The estimated dose derived from two calibration curves for gamma-rays and electron beams was in good agreement. The thin-film polyethylene-alanine dosimeter can be useful as a reference dosimeter for medium energies of electron beams (∼2 MeV) as well as for comparison of radiation effects on various materials for photons and electron beams.

Both interleukin 1 alpha (IL-1 alpha) and tumor necrosis factor alpha (TNF alpha) stimulated the production of interleukin 8 (IL-8) by synovial cells in time and dose dependent manners. Enhanced chemotactic activity of polymorphonuclear cells (PMN) in culture supernatants of synovial cells was neutralized with anti-IL-8 antibody, thus showing synovial cells to be capable of secreting IL-8 which may contribute to PMN accumulation in rheumatoid inflamed joints.

Although a Chinese landrace of barley, Mokusekko 3, is completely resistant to all strains of Barley yellow mosaic virus (BaYMV) and Barley mild mosaic virus (BaMMV), and is known to have at least two resistant genes, rym1 and rym5, only rym5 has been utilized for BaYMV resistant barley breeding in Japan. In order to clarify the effect of rym1 on BaYMV and BaMMV, and to utilize the gene for resistant barley breeding, the susceptibilities of only rym1 carrying breeding lines against BaYMV and BaMMV were investigated. In the assessment of resistance to BaYMV-I, 341 F(2) populations derived from a cross between the resistant line Y4 with only rym1 and the susceptible cv Haruna Nijo shows that the segregation loosely fits a 1R:3S ratio (0.05P0.01), suggesting that the resistance is controlled by a single recessive gene, rym1. Further, none of the F(3) lines derived from the nine resistant F(2) plants showed any disease symptoms in the field infected by BaYMV-I. The same nine F(3) lines showed almost the same agronomic characters in the field infected by BaYMV-III as those in the uninfected field, apart from the symptom of showing numerous mosaics. This result indicates that the gene rym1 has an acceptable level of resistance to BaYMV-III. In the assessment of resistance to BaYMV-II, BaMMV-Ka1 and -Na1, an artificial infection method was adopted and the susceptibilities to those viruses were investigated. Although the control varieties, Ko A and Haruna Nijo, were infected with all of them, the rym1 gene carrying BC(2)F(3) lines were completely resistant to all strains. In summary, rym1 is completely resistant to BaYMV-I, -II, BaMMV-Ka1 and -Na1, and has an acceptable level of resistance to BaYMV-III. This study concludes with a discussion of the reason why the important resistance gene rym1 was eliminated along with resistant cultivars during breeding for resistance to BaYMV.

We examined the effects of artificial circulation by pulsatile and non-pulsatile flow on microcirculation in the brain from the viewpoints of circulation and metabolism in the brain. A centrifugal pump was fixed in the bypass in the right heart of 10 pigs. In 5 of the 10 pigs, a pulsatile flow pump was fixed in the bypass in the left heart (P group), and in the remaining 5 pigs, a centrifugal pump was fixed in the bypass in the left heart (NP group). Hemodynamics were periodically monitored for 3 hours while maintaining about 100 mmHg of the mean aortic pressure. Intracranial pressure (ICP), cerebral tissue blood flow and cerebral blood flow (CBF) were measured and compared with the initial values. As the parameters of metabolism in the brain, the cerebral oxygen consumption and lactic acid - pyruvic acid ratio were evaluated. If the cerebral blood flow was reduced by cardiogenetic shock, we suggest that blood circulation and metabolism in the brain were maintained by artificial circulation. It also indicated that there was no significant difference in blood circulation and metabolism in the brain between artificial pulsatile and non-pulsatile flow circulation.

A seventy-three-year-old man was treated for ventricular septal perforation with Gelatin Resorcin Formalin (GRF) glue. The patient died of multiple organ failure 36 days after the surgery. In autopsy, macroscopically, the inferior wall was reconstructed successfully by the GRF glue. Furthermore, microscopic study revealed the excellent growth of collagen and elastic fiber where the GRF was glued. No infiltration of inflammatory cells was evident. There have been no reports that the safety and efficacy of GRF glue was pathologically proven in an autopsy case.

To investigate the diagnostic value of the serum concentrations of KL-6, a mucinous glycoprotein expressed on type II pneumocytes, for interstitial pneumonia (IP) in various collagen diseases.Serum KL-6 levels were measured by ELISA.The mean values and the positive rates of serum KL-6 levels for patients with rheumatoid arthritis, systemic sclerosis, or polymyositis/dermatomyositis with IP were significantly higher than those without IP. Sensitivity, specificity, positive and negative predictive values of serum KL-6 level for IP associated with collagen diseases were 60.7, 98.9, 97.4, and 77.1%, respectively. The mean serum KL-6 level of patients with active IP was significantly (p = 0.0001) higher than that of patients with inactive IP. Serum KL-6 levels increased with the deterioration of IP, while the successful treatment of IP resulted in a significant decrease of these levels.Serum KL-6 concentration levels are a useful marker for diagnosis and evaluation of the disease activity of IP associated with collagen diseases.

We investigated mid-term results of the patients with an ATS bileaflet valve in our institution. In the past 6 years, 69 patients received valve replacement with an ATS valve. We assessed the changes of serum lactate dehydrogenase (LDH) level in the hospital, and the valve's closing sound. The serum LDH level had almost normalized one week postoperatively and they have maintained normal levels since then. According to the questionnaire about the valvular sound at a random period after surgery, it was unnoticeable in 61 (88.4%) of the patients with ATS valve. In the 8 patients (12.6%) who recognized the valve sound, 7 of them were reoperation cases. As to the frequency analysis for the valve's closing sound, the sound peak was indicated at around 1.2 kHz in the patients with ATS valves. In patients with St. Jude Medical (SJM) valves, it appeared not only around 1.2 kHz but also around 2 to 7 kHz. Postoperative cerebral infarction was complicated in one patient. Mortality occurred in 4 (5.7%) of the patients with ATS valves. The follow up periods were from one to 66 months. Thromboembolic event free and actuarial survival rate in the patients with ATS valves were 98.6% and 94.2%, respectively. These results indicated that the ATS valve is considered to be a safe valve and mid-term follow-up shows excellent results in terms of the patients quality of life.

This study was performed to investigate the efficacy and safety of cyclosporin A (CsA) for the treatment of interstitial pneumonia (IP) associated with collagen diseases in Japan.Questionnaires were sent to 36 hospitals specializing in collagen diseases.Fifty-eight patients (7 polymyositis (PM), 19 dermatomyositis (DM), 7 systemic sclerosis (SSc), 7 rheumatoid arthritis (RA), 2 mixed connective tissue disease (MCTD), 1 systemic lupus erythematosus (SLE) and 1 Sjögren's syndrome (SS), 1 RA + SSc, 2 PM + SSc, 1 DM + SLE, and 10 idiopathic interstitial pneumonia (IIP) with IP were treated with CsA at 14 hospitals. IP was classified into the acute or chronic type. In the PM/DM group (7 PM, 19 DM, 2 PM + SSC, 1 DM + SLE), 65.5% were the acute type. In the other collagen disease group (7 SSc, 7 RA, 2 MCTD, 1 SLE, 1 SS, and 1 RA + SSc) and IIP group, 36.8% and 50% were the acute type, respectively. Mean dosages of CsA were 3.7 +/- 1.3 mg/kg/day for the PM/DM group, 3.0 +/- 1.0 for the other collagen disease group, and 3.8 +/- 4.8 for the IIP group. Oral corticosteroids were administered in combination with CsA in 100, 73.7, and 70% of the patients with PM/DM, other collagen disease, and IIP groups, respectively. CsA was effective for 72.2, 33.3, and 25% of the acute IP cases in the PM/DM, other collagen disease, and IIP groups, respectively. CsA was effective for 50.0, 50.0, and 60.0% of chronic IP cases in the PM/DM, other collagen disease, and IIP groups, respectively. Twenty-three adverse effects were observed, but most of them ameliorated upon withdrawal or reduction of the CsA dose.CsA is effective for the treatment of acute type IP associated with collagen diseases, especially PM/DM. To perform a prospective multi-center trial, standards for the recruitment of patients, efficacy assessments, and trial course and treatment should be determined carefully.

Twenty-six patients were treated by surgical procedure for aortic diseases with use of Gelatin Resorcin Formalin (GRF) glue. They consisted of 25 cases of emergency surgery for type A acute aortic dissection (AAD) and one elective case of distal arch aneurysm. Fifteen patients had moderate to massive aortic regurgitation (AR). We applied GRF glue to adhere the false lumen. It was further applied to anastomosed stitches from the outer side of the aorta. We evaluated the intraoperative effects of it in terms of adhesion and hemostasis and postoperative aortic regurgitation. Furthermore, the mid-term survival rate was investigated. In all cases, the 2 layers were able to be adhered successfully. Furthermore, it was very easy for suturing to pass through the aortic wall, even though the aortic stump was very hard. However, in the distal arch aneurysm case, additional sutures were needed to control the bleeding from the anastomosis. In postoperative aortography, residual AR was found in only one case. Operative deaths were indicated in 3 cases (11.5%). One patient died of hepatic failure on the 9th postoperative day. The other patients died of multiple organ failure. There were 3 cases of late death. The actuarial survival rate at 35 months was 76. 9%. According to these results, we recommend that GRF glue is very effective to reinforce the diseased aortic wall and will improve long-term survival. However, it is considered that the hemostasis effect of GRF glue is not sufficient to be used on anastomosed stitches from the outer side of the aorta.

A Jostra Rota Flow centrifugal blood pump was clinically applied for a cardiopulmonary bypass (CPB) of an ascending aortic replacement for type A aortic dissection. The patient was a 68-year-old female with Stanford type A, DeBakey type II thrombosed aortic dissection complicated by cardiac tamponade and moderate aortic regurgitation. The surgery was carried out on December 22, 1998. The air inside the pump was easily and quickly removed, and its mode of control was excellent. The pump flow during the operation was maintained at about 2.2 l/m2. Total CPB time was 179 minutes. Macroscopically and microscopically, there were no thrombi inside the pump, after usage. The postoperative course was uneventful. The clinical use of this pump was the first case in Japan. This pump is excellent in the ease by which it's controlled due to its compact size and low weight. Furthermore, the Rota Flow console can be fully integrated in the HL-20 heart-lung machine, and these systems have pulsatile flow mode possibility. This pump is suitable not only for the main pump of CPB but also circulatory support.

Objective: To investigate the immunopathological significance of CD40=CD40 ligand system for B cell hyperactivation in SLE patients, the expression and the function of CD40 on B cells were compared with those of normal controls.Methods: Expression of CD40 was evaluated by flow cytometry. DNA synthesis of B cells were measured by3H–TdR incorporation. Antibody production was assessed by ELISA.Results: There was no significant difference between SLE and normal controls in CD40 expression on peripheral blood B cells. Recombinant CD40 ligand-leucine zipper fusion protein (CD40L-LZ)3significantly enhanced 3H ÿ TdR incorporation by both SLE and normal B cells–P < 0:01ƒ. H ÿ TdR incorporation of SLE B cells without stimuli (P < 0:001) and with CD40L-LZ stimulation (p < 0:05) were significantly lower in SLE patients compared with normal controls. Active SLE B cells spontaneously produced significantly larger amounts of total IgG than normal B cells (P < 0:05). CD40L-LZ significantly increased the production of total IgG by SLE B cells (P < 0:05), but not by normal B cells. Active SLE B cells spontaneously produced IgG anti-dsDNA and IgG anti-ssDNA antibodies. CD40L-LZ significantly increased the production of these autoantibodies by SLE B cells (P < 0:05). B cells from normal controls do not produce these autoantibodies spontaneously nor in response to CD40L-LZ.Conclusion: These findings indicate that signalling via CD40 plays an important role in B cell proliferation and autoantibody production in human SLE.

To determine the immunopathological significance of CD40/CD40 ligand (CD40L) interaction in rheumatoid arthritis (RA).The expression of CD40 ligand (CD40L) in synovial tissues (ST) from patients with RA was examined by immunohistochemistry. Tumor necrosis factor-alpha (TNF-alpha) was measured by ELISA. Expression of CD40 on ST cells was quantified by anti-CD40 monoclonal antibodies and 125I labelled anti-mouse IgG.Immunohistochemistry showed CD40L+ T cells in RA ST. Ligation of CD40 on RA ST cells significantly increased the production of TNF-alpha in a dose dependent fashion. Adherent, but not non-adherent, fraction of ST cells responded to ligation of CD40 to produce TNF-alpha. Interferon-gamma (IFN-gamma), interleukin 4 (IL-4), or IL-13 acted synergistically with CD40 ligation to enhance TNF-alpha production by ST cells. IL-10 exerted inhibitory effects on both CD40 ligation induced and CD40 ligation plus IFN-gamma induced TNF-alpha production by ST cells.These data indicate activated T cells participate in synovial inflammation of RA via CD40L to stimulate the production of TNF-alpha by ST cells. The effect of CD40 ligation is modulated by the presence of several cytokines, e.g., IFN-gamma, IL-4, IL-10, and IL-13.

In this study, we used alpha-human atrial natriuretic peptide (hANP) from staring on cardiopulmonary bypass and evaluated for the hemodynamics, ANP, renin activity, aldosterone, urine volume, glomerular filtration rate (GFR) and so on. The hANP decreased renin activity, aldosterone, systemic vascular resistance and increased urine volume, GFR and use of furosemide and KCL were decreased. We concluded that hANP was effective for hemodynamics, renal function and hormonal release on intra and post-operation in cardiac surgery, and low dose continuous infusion of alpha-hANP from staring on cardiopulmonary bypass will be expected as a newly application.

We report a case of systemic sclerosis (SSc) complicated with benign pneumoperitoneum without apparent pneumatosis cystoides intestinalis (PCI). A 43-year-old woman was admitted to our hospital because of prominent abdominal distension in April 1997. Raynaud's phenomenon has been detected since 1991. She was suffering from recurrent diarrhea, constipation, and subileus. The diagnosis of SSc was made in 1996 based on the sclerosis in her face, forearms, and chest, and hypomotility of the esophagus. On admission, she presented no signs of peritoneal irritation. The laboratory data revealed that white blood cell count was 7,400/mm3 and C-reactive protein was 0.1 mg/dl. Chest and abdominal roentgenograms showed massive free air under the diaphragm, dilatation of small and large intestine, and air-fluid level. PCI was not apparent. Pneumoperitoneum was improved after four weeks with intravenous hyperalimentation. But she presented recurrent severe diarrhea and high fever whenever she tried to take food orally. Klebsiella pneumoniae was proved in her jejunal juice by bacteriologic examination. Intravenous prostaglandin F2 alpha and oral fosfomycin calcium intake made her condition better. Benign pneumoperitoneum without PCI is rarely reported in the patients with SSc. In her condition, weakness of intestinal wall, hypomotility of intestine, unusual bacterial overgrowth, and elevated intraluminal pressure made intraluminal gas go through the wall of the fragile intestine of SSc. As operation of intestine of SSc usually cause miserable outcome, pneumoperitoneum accompanied with SSc even if PCI is apparent or not must be treated with conventional manner while there is no signs of peritoneal irritation.

The patient, a 35-year-old woman, had been diagnosed as SLE since she developed butterfly rash, arthritis and hair loss with positive antinuclear antibody, anti-DNA antibody, and LE cells in 1989, and treated with daily 20 mg prednisolone (PSL). She had been suffering from nausea, vomiting and waterly diarrhea since 1992. In June 1995, she noted pollakisuria and sense of residual urine, followed by dysuria and nocturia in October. She was admitted to our hospital in January 1996 with progressive gastrointestinal and urinary symptoms. Computerized tomography (CT) depicted thickening of the wall of intestine and bladder, diminished volume of bladder, and bilateral hydronephrosis and hydroureter. Biopsy of the bladder revealed erosion of mucosa and moderate infiltration with inflammatory cells. The diagnosis of lupus cystitis and peritonitis was made and she was initially given intravenous methylprednisolon pulse therapy (500 mg/day) for 3 days, and then switched to 100 mg of daily intravenous PSL. She responded partially to this regimen, but gradually developed gastrointestinal and urinary symptoms again when PSL was tapered down to 70 mg/day. Therefore, monthly intravenous cyclophosuphamide pulse therapy was started. With this therapy, her bladder and bowel symptoms improved, and then the thickness of her bladder and intestinal wall, and the bladder volume normalized. Five months after institution of therapy, PSL was successfully tapered down to 30 mg/day and she was discharged. Intravenous cyclophosphamidepulse therapy is a choice of treatment for steroid-resistant lupus cystitis and peritonitis.

Increased concentration of serum alkaline phosphatase (ALP) is a common feature in rheumatoid arthritis (RA), although its origin remains unclear. The aim of this study is to analyze the origin and clinical significance of the elevated ALP value in RA. In 123 RA and 63 age- and sex-matched OA (osteoarthropathy) patients, concentrations of total ALP and its isozymes in serum and synovial fluid were studied. Serum CRP, Fe, ferritin, and Cu values were examined, respectively. The expression of ALP as protein was also investigated by using an enzymehistochemical and an immunohistochemical staining methods. Serum ALP values were elevated in 37.4% of RA (245.2 +/- 91.2 IU/L), and significantly higher than those of OA (192.3 +/- 45.2 IU/L: P0.01, RA v.s. OA). The serum CRP, and ferritin values each had a relation with the serum ALP activity. Fluid ALP concentration of RA was 110.3 +/- 40.1 IU/L, and that of OA, 83.6 +/- 15.0 IU/L (P0.05), respectively. In RA, a predominant isozyme was liver-type one both in the sera (91%) and the synovial fluid (59%). However, this result means that bone-type one was more abundant in the synovial fluids (41%) than those in the sera (9%). An enzymehistochemical and an immunohistochemical studies revealed that ALP was positive in a perivascular area, sublining cells, and a part of vascular endothelium in RA. In contrast, the synovial tissue from OA and a healthy patient exhibited only a weak staining. In RA, a positive correlation between the elevation of serum ALP and the disease activity was confirmed. Furthermore, we elucidated that ALP is produced in RA synovium.

A 20-year-old woman with arthralgia, serositis, thrombocytopenia, proteinuria, muscle weakness, elevated creatinine kinase, and positive anti-Sm antibody was diagnosed as having polymyositis and systemic lupus erythematosus (SLE). She had persistent high temperature, sinus tachycardia, hyperhidrosis, mydriasis, visual disturbance, hallucination, and loss of consciousness. Levels of plasma adrenaline, noradrenaline, and dopamine and cerebrospinal fluid interleukin (IL)-6 and IL-8 were all high. A diagnosis of sympathetic hyperfunction accompanied by central nervous system (CNS) involvement in SLE was made parenteral. Pulse administration of high dose corticosteroid therapy was effective. This is the first reported case of a connective tissue disease with CNS involvement manifesting as sympathetic hyperfunction with high plasma catecholamine levels.

A 26-year-old female was admitted to Aoyama Hospital in February 1996, for evaluation of abnormal chest shadows and polyarthritis. She visited our clinic in December 1995 with complaints of fever, fatigue, and polyarthralgia which lasted for 3 weeks. Two weeks later she developed erythema nodosum on her lower legs with the exacerbation of polyarthritis. Erythrocyte sedimentation rate was 108 mm/hr and CRP 4.9 mg/dl. A chest radiograph showed hilar lymphadenopathy and multiple nodular shadows in both lung fields. On admission, she had arthritis of the shoulders and knees, erythema nodosum on her lower extremities, and keloid-like skin lesion on her left knee. Thoracoscopic lung biopsy of nodular lesion and skin biopsy of keloid-like lesion revealed noncaseating granuloma of epithelioid cells with lymphocytes, macrophages, and giant cells, confirming the diagnosis of sarcoidosis. She was cured in three months, and was well and free of the symptoms thereafter. Löfgren's syndrome is acute sarcoidosis, characterized by arthritis, erythema nodosum, and bilateral hilar lymphadenopathy. This syndrome is common in Europe and is closely related to HLA-B8 and DR-3. The frequency of HLA-B8 and DR-3 in Japanese is almost 0%, explaining the rare onset of this syndrome in Japan. Our case is the second report of typical Löfgren's syndrome in Japan, although the patient did not have these HLA loci.

To investigate the correlation of HLA class I and class II antigens and alleles with various forms of myositis in Japanese patients.Eighty-four Japanese patients with myositis [22 with polymyositis (PM), 46 with dermatomyositis (DM), 16 with myositis overlapping with other collagen vascular diseases] were typed serologically for HLA-A, B, C antigens. HLA-DRB1, DQA1, and DQB1 alleles were determined by polymerase chain reaction dependent DNA typing methods. Fifty-eight Japanese controls were typed serologically while HLA-DRB1, DQA1, and DQB1 allele typing was carried out in 175, 95, and 104 controls, respectively.HLA-B7 was higher in patients than controls [20.2 vs 6.9% in controls: p=0.02, odds ratio (OR)=3.4]. The increase of HLA-B7 was largely dependent on the increase in overlap patients (37.5%; p=0.005, OR=8.1). HLA-A24 and B52 were significantly decreased in PM as compared to DM, while CW3 was significantly increased in PM versus DM. DRB1*08 alleles were significantly increased in patients (36.9 vs 20.5% in controls; p=0.004, OR=2.3), especially in PM and DM. DQA1*0501 and DQB1*0301 were significantly decreased in patients [4.8 vs 13.7% in controls; p=0.04, OR=0.32, and 8.3 vs 20.2% in controls; p=0.02, OR=0.36, respectively].HLA-class I and class II alleles associated with Japanese patients with myositis may be different from those associated with Caucasian patients.

To determine clinical variables useful in predicting the prognosis of patients with early rheumatoid arthritis (RA) by investigating the relationship between clinical variables and radiological progression.One hundred eighteen patients with early RA whose symptoms developed within the previous year were enrolled in a prospective study. Data from the 98 patients who completed the 2 year study were analyzed, using the number of erosive joints and Larsen's score as the outcome of RA.Increases in the number of erosive joints at 12 months after entry into the study were significantly correlated with the number of swollen joints (r = 0.510), erythrocyte sedimentation rate (ESR) (r = 0.404), and C-reactive protein (CRP) (r = 0.487) at 6 months. The same results were seen using Larsen's score as the measure of outcome. The average number of erosive joints or mean Larsen's score at 12 months was higher in patients whose levels of CRP were high at 6 months and suppressed by 12 months, but increased much less in patients whose levels of CRP were successfully suppressed by 6 months. More joint erosions were noted in patients with positive rheumatoid factor (RF) than in RF negative patients.Joint erosions appeared with a certain time lag after active synovitis. Earlier introduction of effective treatment is recommended for the prevention of RA joint damage. The presence of RF, number of swollen joints, ESR, and levels of CRP at 6 months after starting therapy are the most useful variables to predict radiological progression in patients with early RA.

The effectiveness of methotrexate (MTX) in treatment of rheumatoid arthritis (RA) was evaluated by following the course of 232 cases. The number of cases in which MTX treatment was assessed as effective amounted to 149 (64.2%), and among these the number of cases in which the effect was excellent amounted to 59 (25.4%). As for the time required to achieve the therapeutic effect, effectiveness was evident within one month in most cases and the more prominent was the result, the shorter was the time required to achieve the effect. In analysis of it's effectiveness, no relationship to the patient's background such as morbidity period, the extent of inflammation, or the period of administration of anti-rheumatic drugs was observed and this drug seems promising for treatment of severe inflammation in cases of RA with prolonged course enabling application to a wide range of patients. Also, therapeutic effectiveness was observed in a group of elderly patients, who were more than 65 years old. However, in such cases, MTX should be administered carefully because of its reported strong adverse effects. Its effectiveness and adverse effects have been shown to be dose-dependent. Therefore, as the optimum dosage of MTX, it is recommended to administer a dose of 5.0 mg/week initially for an evaluation period of two months and in those cases in which no effect is observed, the dose is then increased to 7.5 mg/week.

Rheumatoid arthritis(RA) is a chronic systemic inflammatory disease of unknown etiology, characterized by synovial inflammation and local tissue destruction. For many years, the traditional approach for the therapy of RA was the therapeutic pyramid. Recently, the beneficial effects of the pyramid strategy have been questioned because the long-term outcome of RA continues to be disappointing. Three developments stimulated a change in thinking: first, the increasingly precise understanding of pathogenesis, second, the availability of biological agents and, third, the methods of evaluation for RA therapy. Therefore, many treatment strategies for RA, almost of which prefer the earlier introduction of disease-modifying antirheumatic drugs, have been proposed. Several representative strategies are reviewed in this paper.

To characterize the American College of Rheumatology core set of disease activity measures for rheumatoid arthritis (RA) clinical trials (ACR core set measures) and the ACR definition of improvement of RA (ACR improvement definition), we studied 42 Japanese patients with active RA who were treated with DMARDs including mizoribine. Each patient's disease activity was assessed at the time of enrollment to the study and after 24 weeks using the ACR core set measures as well as the physical global assessment through the conventional measures. Twenty-five (60%) patients were discerned as showing improved by physicians through the conventional measures. This decision appeared to be based on improvement in Lansbury activity index (LAI) and C-reactive protein (CRP) value. Twelve of the 25 "improved" patients satisfied the ACR improvement definition. The 12 patients showed significant improvement in "outcome" measures including patients assessments of pain, disease activity, and physical function, compared to the 30 patients not satisfying the ACR definition. However, no significant differences were observed between these two groups in "process" measures including LAI, tender joint count, swallen joint count, or CRP value. In conclusion, the ACR core set measures including both process and outcome measures have potential to reflect clinical important changes on "real life" of patients with RA.

Objective was to study the significance and the mechanism of action of elastase from polymorphonuclear leukocyte (PMN elastase) in patients with rheumatoid arthritis (RA). The experiments conducted consisted of two phases. Firstly, articular cartilage and synovia from 8 patients with RA undergoing total knee replacement were obtained, and the gelatinolytic enzyme activity was extracted with 2M guanidine hydrochloride. The gelatinolytic activity of each tissue was measured to confirm that the activity was due to PMN elastase by using an antihuman leukocyte elastase antibody. Secondly, the levels of PMN elastase-alpha 1 proteinase inhibitor complex (EIC) in the blood and synovial fluid of 170 patients with RA were measured by immunoassay. The results were as follows: 1. Gelatinolytic activity was shown to be mainly due to PMN elastase, and found to be highest in cartilage and synovia in RA joints. 2. The EIC levels in plasma of RA patients were significantly higher than those in gout and osteoarthritis (OA), and the EIC levels increased according to the stage of articular cartilage destruction. Moreover, the EIC levels in synovial fluid of RA patients were higher compared to those of OA patients. The activity of PMN elastase was elevated in destructive joints of RA. With the progression of articular cartilage destruction, EIC levels in plasma of RA patients increased as well. We suggest that PMN elastase may play a significant role in RA disease.

To compare the histological characteristics of the synovium between seropositive and seronegative rheumatoid arthritis (RA), synovial tissue was obtained from 19 patients with rheumatoid factor-positive (RF+) RA, 11 with rheumatoid factor-negative (RF-)RA and 11 non-RA controls.There were no differences in the frequency of each histological feature or histological scores between RF+ and RF-RA. However, significant differences in the frequency of histological findings such as lining cell proliferation and inflammatory cell infiltration were found both between RF+ RA and non-RA controls, and between RF-RA and non-RA controls. Analysis of clinical parameters and histology in all RA patients revealed that the level of serum C-reactive protein and the erythrocyte sedimentation rate were directly correlated with the inflammatory cellular infiltration score. Immunohistological staining using a monoclonal antibody against IgM rheumatoid factor (RF) was positive in some plasma cells in the synovium of both RF+ and RF-RA patients, while no IgM-RF-positive cells were observed in the synovium of non-RA controls.RF serostatus does not necessarily reflect the histology of synovial inflammation.

The problem of nonsteroidal anti-inflammatory drug (NSAID)-induced gastrointestinal toxicity was reviewed by members of the Asia Pacific League of Associations for Rheumatology (APLAR) in a consensus conference in September 1992. This paper by the participants presents the consensus conclusions incorporating knowledge from recent publications. There had been a high level of concern that much of the toxicity had resulted from extensive and indiscriminate prescribing of NSAIDs. The implementation of evidence-based guidelines was considered likely to be able to effect a substantial reduction in toxicity without significant loss of overall therapeutic benefit. The evidence from which such guidelines could be developed is critically appraised.

Human IgM that express the variable region genes of the VH3 family bind staphylococcal protein A (SPA). We previously reported that the SPA-binding IgM can be divided into two groups based on the differential binding avidities for solid-phase SPA. To study the molecular basis for these differences, we cloned B cells from human blood by EBV transformation. The nucleotide sequences of the expressed Ig heavy chain genes were determined on 20 B cell clones that produce SPA-binding IgM. The germ-line VH3 gene usage in IgM with high avidities for SPA were distinct from the germ-line VH3 genes used in IgM with low avidities for SPA. There was no correlation in the usage of D or JH genes or in the usage of light chains in IgM according to the SPA binding avidity. These results suggest that the differential binding avidities for SPA are at least partly due to specific germ-line VH3 gene usage. An investigation of direct binding of SPA to the synthetic peptides corresponding to the portions of the variable regions of SPA-binding and non-SPA-binding IgM showed that the peptides corresponding to the VH3 family specific framework region 3 sequences had significant SPA binding capacities, while the peptides corresponding to the other subdomains and those corresponding to framework region 3 of the reported VH3 sequences from non-SPA-binding IgM showed little or no binding. It is of interest that the Ig-framework region 3 subdomain corresponds to the fourth hypervariable region, which in the TCR-beta chain has been implicated as a critical site for T cell superantigen binding.

To analyze the possible adverse effects of low dose methotrexate (MTX) therapy, 276 patients with rheumatoid arthritis (RA) were examined retrospectively. One hundred and seven patients (39%) experienced 113 adverse events : 57 showed liver dysfunction, 24 gastrointestinal complaints, 13 cutaneous symptoms, 6 respiratory symptoms, and 6 malignancies. Interestingly, 3 patients developed a dry cough without infiltration nor interstitial shadow on chest X-ray. The cough was rapidly resolved by discontinuation of MTX, but it recurred in 1 patient when MTX was re-administered. This finding might suggest a close association between MTX administration and the occurrence of dry cough. Of the 6 patients with malignancies diagnosed during MTX therapy, 2 showed malignant lymphoma, 2 lung cancer, 1 breast cancer and 1 colon cancer. MTX might have an oncogenic potential in RA because the coincidence rate, especially with respect to lymphoma, was significantly higher than estimated in a normal population.

In a study to evaluate the usefulness of DMARDs combination therapy for RA, AF and MTX were concurrently given to RA patients who had responded poorly to over three months of monotherapy of either AF or MTX. The study was composed of two stages. In the first stage, patients were concurrently given AF and MTX for six months in order to evaluate the efficacy of combination therapy. In the second stage, patients who had responded to the earlier combination therapy were again put on monotherapy of the additive DMARD. Safety evaluation was conducted with 126 patients, and both efficacy and utility were evaluated in 100 patients. Lansbury index for RA significantly improved in both groups of patients starting with the AF and followed by the MTX combination (Group I) and those who started with MTX alone followed by the AF combination (Group II). The ratio of patients who achieved slight improvement or better in the overall improvement rating was significantly higher in Group I at 74.6%, vs. 51.1% in Group II patients. Ten patients (16.9%) and 2 patients (4.9%) were switched to their additive DMARD monotherapy of MTX and AF respectively, having responded to the combination therapy in stage I with slight improvement or a better rating. Adverse events were observed in 44 patients (34.9%), but the combination therapy neither increased the incidence of adverse events nor caused new adverse events. Combination therapy of AF and MTX appeared to be useful both in terms of efficacy and safety for patients who have experienced the dwindling effect of monotherapy.

The 5′-terminal half of RNA 1 and whole of RNA 2 of barley mild mosaic bymovirus Na1 strain (BaMMV-Na1) were sequenced to give together with the published data its complete genomic sequence. BaMMV-Na1 RNA 1 and RNA 2 consist of 7 263 and 3 516 nucleotides, excluding the 3′ poly A tails, respectively. RNA 1 encodes a single large polyprotein of 2 258 amino acids (Mr 256 K), containing eight putative functional proteins, and RNA 2 also encodes one polyprotein of 891 amino acids (Mr 98 K), containing two functional proteins. These functional proteins are arranged in the same manner as in RNA 1 and RNA 2 of barley yellow mosaic bymovirus (BaYMV), and significant amino acid sequence homology (25–58%) exists between the proteins of the two viruses. The BaMMV-Na1 proteins show less amino acid sequence homology (18–32%) with the corresponding proteins of potyviruses or rymoviruses than with those of Ba YMV. Comparisons of the BaMMV-Na1 proteins with the corresponding proteins of other partially sequenced BaMMV isolates show 87–98% amino acid sequence identity. There is 91–94% nucleotide sequence identity between the 3′ non-coding regions (NCRs) in RNA 1 or RNA 2 of BaMMV-Na1 and other BaMMV isolates, but only 68–72% identity between the 5′ NCRs in RNA 2 of BaMMV-Na1 and other BaMMV isolates.

The expression of a series of adhesion molecules (the integrin family, the immunoglobulin superfamily, CD44 and the selectin family) on peripheral blood mononuclear cells (PBMC) from RA patients was investigated by flow-cytometry. L-Selectin (CD62L) in the selectin family was more significantly expressed on PBMC from RA patients as compared to those from normal controls. Further, RA patients exhibited a slight but significant increase of VLA-alpha 2 (CDw49b), p150,95 (CD11c), and VNR-beta (CD61) in the integrin family. The enhanced expression of L-selectin was positively correlated with disease activity. An increase in the proportion of L-selectin+CD4+ cells in PBMC from patients with RA and its clinical significance is reported.

To determine whether intermittent rather than daily administration of D-penicillamine (D-Pen) would effectively reduce the incidence of adverse effects without significantly diminishing the clinical benefits.We conducted an open prospective trial comparing daily and intermittent schedules. Among 76 Japanese patients with rheumatoid arthritis (RA), 37 underwent daily treatment with D-Pen while 39 were given D-Pen intermittently (every Monday, Wednesday, and Friday).The mean D-Pen dose was 166.8 and 99.4 mg/day for daily and intermittent groups, respectively, the difference being highly significant (p0.0001, Mann-Whitney's U test). The incidence of adverse effects was significantly lower in the intermittent group. Both schedules significantly reduced the activity of RA, as evaluated by clinical and laboratory variables. No significant differences were observed in the degree of improvement between the 2 schedules.Intermittent therapy with D-Pen is an effective treatment for patients with RA and its higher degree of flexibility can lead to maximum efficacy for management of patients with RA.

A clinical trial was conducted in 22 SLE patients with central nervous system (CNS) disorder in which the efficacy of pulse methylprednisolone suleptanate at the dose of 400 mg or 800 mg (as methylprednisolone) was assessed. The symptoms of CNS disorder disappeared within 40 days after pulse therapy in all of the 16 patients with organic brain syndrome (OBS). No improvement in the symptoms took place in any but one of the five patients who had cerebrovascular disorder. One SLE patient with depression showed improvement 55 days after pulse therapy. In the patients with OBS who had not received pulse therapy until 28 days or more after onset of CNS disorder, the symptoms disappeared in 20 days or more in both 400 mg and 800 mg dose groups. On the other hand, five of the six patients given the dose of 800 mg within 10 days of occurrence of the disease experienced a complete relief of the symptoms in 10 days after pulse therapy. However, at least 13 days were required for complete relief in all the four patients of the 400 mg group. The adverse reactions reported consisted of hyperlipemia, diabetes mellitus, and infections such as thrush or herpes zoster. The above results suggest that methylprednisolone pulse therapy is useful in the treatment of CNS disorder associated with SLE, particularly in patients with OBS who are given the dose of 800 mg early after onset of the disease.