Isotypes of rheumatoid factors in rheumatoid arthritis and chronic liver diseases

We studied isotype-specific rheumatoid factors (RFs) to clarify their significance in rheumatoid arthritis (RA) and to verify the difference in RF isotypes between RA and chronic liver diseases (CLD). Isotype-specific RFs in RA and in CLD were measured by enzyme-linked immunosorbent assay (ELISA). Most sera (n = 51, 94.1%) from RA patients contained some kind of RF isotypes (92.1% for IgM RF, 76.4% for IgG RF, and 43.1% for IgA RF), and seronegative RA by ELISA was seen in only 11.8% (n = 6). The most characteristic combination of RF isotypes in active RA was IgG, IgA, and IgM. This combination of RF isotypes changed to IgG plus IgM, according to the diminution of RA activity; then, we found only IgM RF in inactive RA. The titers of each RF isotype also decreased in parallel with the activity of RA. IgA RF seemed to be the most sensitive factor for evaluating the activity of RA. In CLD, almost the same high frequency (n = 49, 89.8% for IgM RF, 59.2% for IgG RF), with the same titer levels seen in RA, was observed. On the other hand, IgA RF was significantly lower in frequency (n = 9, 18.4%) and in titer, compared with the finding in RA. Surprisingly, even in CLD, true seronegativity by ELISA was also found in very few patients (n = 4, 8.1%). In CLD, positive RFs detected by agglutination assay were seen more often in chronic hepatitis than in liver cirrhosis. In RA patients, significant associations of IgA RF and the serum concentration of IgA, and IgG RF and the serum concentration of IgG, were observed. On the other hand, in CLD patients, significant associations of IgG RF and the serum IgG concentration, and of IgM RF and the serum IgM concentration, were observed. These results indicated that IgA RF in active RA is the most characteristic RF isotype distinguishing it from other nonrheumatic diseases, as well as from inactive RA. RF isotypes reflected the background polyclonal B-cell activation in different manners in both diseases. In CLD, RF isotypes seemed to be disease-related immunological disorders reflecting disease progression. Received: February 17, 2000 / Accepted: July 5, 2001     

Multiplex polymerase chain reaction assay for selective detection of Salmonella enterica serovar typhimurium

A multiplex polymerase chain reaction (PCR) assay was developed for the identification of Salmonella enterica serovar Typhimurium. Three sets of primers were designed for detecting O4, H:i, and H:1,2 antigen genes from the antigen-specific genes rfbJ, fliC, and fljB, respectively. These were evaluated in a multiplex PCR assay by using DNAs from S. enterica serovar Typhimurium, 15 other Salmonella serovars, and 8 non-Salmonella enteric pathogens. Multiplex PCR proved to be capable of identifying S. enterica serovar Typhimurium specifically and differentiating it from other Salmonella serovars in addition to non-Salmonella enteric pathogens. Thus, this multiplex PCR assay can be practically applied to the identification of S. enterica serovar Typhimurium.     

Nitric oxide production of rat Leydig and Sertoli cells is stimulated by round spermatid factor(s)

In this study, we provide evidence of cell-to-cell interaction between rat germ cells and Leydig or Sertoli cells in relation to nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) messenger RNA (mRNA) expression. As a result of being cultured in a round spermatid-conditioned medium (RSd-CM), NO production in both Leydig and Sertoli cells increased in proportion to the length of the culture period. iNOS mRNA expression in both types of cells also increased in a dose-dependent manner as a result of being cultured with RSd-CM. This increase was detected as early as 3 h and was maintained up to 24 h. In contrast, neither NO production nor iNOS mRNA increased in either type of cell following culture in a pachytene spermatocyte-conditioned medium (PS-CM). Our findings suggest that RSd may control NO production of Leydig and Sertoli cells. This cell-to-cell interaction may be an important mechanism of regulation of testicular function.     

Emergence of malignant lesions within an adenomatous hyperplastic nodule in a cirrhotic liver. Observations in five cases

Five cases of an adenomatous hyperplastic nodule or a similar lesion resected from a cirrhotic liver in which early malignant foci were seen as small nodule-in-nodule lesions are described. These hyperplastic lesions were detected by imaging diagnosis in patients with nonalcoholic cirrhosis, mostly during routine clinical follow-up. In 2 patients, recurrence of hepatocellular carcinoma occurred 11 mo and 15 mo postresection. Thus, these nodule-in-nodule lesions in an adenomatous hyperplastic nodule seem to represent an early stage of hepatocarcinogenesis in humans. In nonalcoholic cirrhotic patients from Japan and Southeast Asia, in whom hepatocellular carcinoma is endemic, an adenomatous hyperplastic nodule or a similar hyperplastic lesion that occurs in cirrhotic livers may be preneoplastic and already committed to malignant transformation.     

Clinical study on the flow murmurs at the defect area of atrial septal defect by means of intracardiac phonocardiography.

In order to study flow murmurs through atrial septal defects, right heart catheterization was performed on 48 patients of secundum type, four of primum type, and five of probe-patent foramen ovale, with the double-lumen phonocatheter of Lewis, at the tip of which barium titanate was mounted. The flow murmurs at the defect area were classified into three patterns: v murmur, atriosystolic murmur, and mid-diastolic murmur. V murmur was continuous, extending from late systole to diastole, of low to medium pitch, closely related to atrial v wave and augmenting with expiration. It had no significant correlation to the ratio of left-to-right shunt. It was recorded in 32 out of 48 cases of secundum type and one of primum type, but not observed in probe-patent foramen ovale. Atriosystolic murmur was noted in 17 of 48 cases of secundum type and one of primum type. It was connected with atrial a wave. Mid-diastolic murmur was found at the defect area in four subjects of secundum type. It was thought to be an independent entity from v murmur and to be another one due to shunt flow through the septal defect, since it had no relation to v wave but it was localized between v and a waves in the pressure curve of the right atrium. It is different in localization from mid-diastolic murmur due to relative tricuspid stenosis at the inflow tract of right ventricle.     

Nitric oxide plays an insignificant role in direct vasodilator effects of calcium channel blockers in healthy humans

Several experimental studies have suggested that the vasodilatory effects of calcium channel blockers (CCBs) are due in part to an endothelium-dependent mechanism. However, it remains unknown whether CCBs directly augment liberation of endothelium-derived dilator substances such as nitric oxide (NO) in the human vasculature. The aim of this study was to examine whether CCBs of several kinds directly increase the bioavailability of NO in forearm resistance vessels. Twenty-four healthy men (mean age 30 ± 2 years) were randomly assigned to three study groups (n = 8 in each), and each group was assigned one of three first-generation CCBs (nifedipine, nicardipine, diltiazem). Subdepressor doses of CCBs [4, 8, 16, 24, and 36 (diltiazem only) nmol/min; for 2 min in each dose] were infused intra-arterially, and forearm blood flow (FBF) was determined plethysmographically. After control FBF responses to CCBs had been measured, a NO synthase inhibitor (N ^G-monomethyl-l-arginine: l-NMMA) was infused intra-arterially, and the FBF response to CCBs was again determined. Further, as a positive control for NO stimulation, acetylcholine (ACh) was also examined before and after l-NMMA in each group. Systemic blood pressure and heart rate did not change significantly during the study protocol. The FBF responses to these CCBs did not differ before and after NO synthase inhibition by l-NMMA (FBF at maximum doses: nifedipine, 8.0 ± 0.8 vs 7.3 ± 0.7; nicardipine, 7.3 ± 1.5 vs 6.5 ± 1.3; diltiazem, 5.7 ± 0.7 vs 4.2 ± 0.7 ml/min per 100 ml: all not significant), although FBF responses to ACh were significantly reduced by l-NMMA. In conclusion, direct NO liberation does not make a significant contribution to the vasodilation associated with first-generation CCBs in healthy human resistance vessels. Received: July 12, 2001 / Accepted: October 19, 2001     

Analysis of chest radiographs of culture positive Legionella pneumonia in Japan, 1980-1990. Working Party for Legionellosis, Japanese Ministry of Health and Welfare]

We analyzed the initial and follow-up chest radiographs of 28 patients with culture-positive Legionella pneumonia, and developed a scoring system to quantitate the severity of radiological findings for pneumonia. Intrapulmonary shadows were observed on the initial chest radiograph in 26 patients, but pleural effusion was noted in only one. In one patient the initial chest radiograph had probably been obtained too early to reveal any pulmonary change. Alveolar shadows were noted on the initial radiograph in 21 (81%) patients, and interstitial shadows in 5 (19%). In ten (38%) patients shadows were present in both lung fields. Shadows were prominent in the middle and lower lung fields. A cavity was noted in only one patient, and pleural effusion was also noted at some time during the clinical course in 19 (70%). A large amount of pleural effusion was observed in four patients. The average pneumonia severity score was 3.3 in the 9 patients who survived, and 5.1 in the 17 who died (p > 0.05). The mortality rate was 53% in the 17 patients with pneumonia severity score of 5 or less and 89% in the 9 patients with a score of 6 or more (p > 0.05). Twelve patients died within one week after the initial chest radiograph was obtained. There were no differences among patients with community-acquired infection with or without underlying disease and those with nosocomial infection in characteristic and extension of shadow, presence of pleural effusion, or pneumonia score. The chest radiograph of Legionella pneumonia include bilateral shadow findings characteristic, pleural effusion and rapid progression of shadow, and are clinically useful for diagnosis.     

A prospective, single-blind trial comparing wireless capsule endoscopy and double-balloon enteroscopy in patients with obscure gastrointestinal bleeding

BACKGROUND: Wireless capsule endoscopy (CE) and double-balloon enteroscopy (DBE) are new methods enabling diagnostic endoscopy of the entire small intestine. However, which of the two is superior is unclear. We therefore prospectively compared the clinical efficacy of CE and DBE. METHODS: We prospectively examined 32 patients with obscure gastrointestinal bleeding. CE preceded DBE by 1-7 days, and all patients underwent DBE twice, by antegrade and retrograde approaches, to evaluate the entire small intestine. Physicians evaluating the results of CE and DBE were blind to the results of the other method. We evaluated diagnosis, diagnostic yield of the two methods, and clinical outcomes. RESULTS: CE revealed abnormal findings in 29 (90.6%) of 32 patients. CE definitively or probably detected the sources of bleeding in 23 (71.9%) of the 32 patients, including angioectasias (eight), erosions (seven), ulcers (five), tumor (one), and hemorrhagic polyps (two). DBE definitely or probably detected the sources of bleeding in 21 (65.6%) of the 32 patients, including angioectasias (seven), erosions (four), ulcers (five), tumor (one), hemorrhagic polyps (two) and diverticula (two). CE yielded more abnormal findings than DBE (CE 90.6%, DBE 65.6%) (P = 0.032), although there were no significant differences in diagnostic yield between the methods. We were able to perform additional treatment or biopsy with DBE in 13 patients, including coagulation therapy (ten), endoscopic mucosal resection (one), biopsy (seven), and extraction of retained CE (two). CONCLUSIONS: Our results demonstrate the superiority of CE in detecting abnormal lesions, and the superiority of DBE in endoscopic management.