Clinical features of liver disturbance in rheumatoid diseases: clinicopathological study with special reference to the cause of liver disturbance

Background: Background: Liver disturbance in rheumatoid diseases results not only from liver disease associated with the rheumatoid diseases themselves but also from various other causes. This study aimed to elucidate the clinical features of liver disturbance in rheumatoid diseases, focusing on the cause of this disturbance. Methods: A clinicopathological study was performed in 306 patients (106 with systemic lupus erythematosus, 71 with Sj?gren's syndrome, 59 with rheumatoid arthritis, 27 with scleroderma, 30 with polymyositis, and 13 with polyarteritis nodosa). Results: Liver disturbance occurred in 43% of these patients and resulted from various causes. Its degree and duration varied from one cause to another. Liver disease associated with rheumatoid diseases was the leading cause of the liver disturbance in these patients and was characterized by mild and transient liver disturbance (maximum alanine aminotransferase [ALT] level during the study period, 68 ± 8 IU/ml; maximum alkaline phosphatase [ALP] level, 410 ± 31 IU/ml; duration of liver disturbance, 6 ± 2 months). Most patients with this type of liver disease showed minimal change in liver histology, although two-thirds of those evaluated by the international scoring system for autoimmune hepatitis (AIH) were classified as “probable” or “definite”. Eight of 14 patients with histologically proven chronic hepatitis or cirrhosis were infected with hepatotropic virus (7 with hepatitis C virus [HCV] and 1 with hepatitis B virus [HBV]). Five of 9 patients in whom the hepatic lesion progressed had hepatotropic virus infection (4 with HCV and 1 with HBV), and the other 4 patients suffered from autoimmune liver diseases. Conclusions: Liver disease associated with rheumatoid diseases was the leading cause of liver disturbance in these patients and was characterized by mild and transient liver disturbance, whereas progressive liver diseases were often associated with hepatotropic virus, mainly HCV, or autoimmune liver diseases. Liver histology is indispensable for differentiating AIH from liver disease associated with rheumatoid diseases. Received: August 27, 2001 / Accepted: January 7, 2002     

A novel mutation Lys273Glu in the cardiac troponin T gene shows high degree of penetrance and transition from hypertrophic to dilated cardiomyopathy.

Familial hypertrophic cardiomyopathy (HC) can be caused by mutations in 9 different genes encoding sarcomere proteins expressed in cardiac muscle. To date, only 13 different mutations in the cardiac troponin T (cTnT) gene have been reported to cause HC. Clinical characteristics and prognosis associated with mutations of this gene have not been well characterized owing to the small size and composition of affected families. The aim of this study was to determine the characteristic phenotype of patients with HC caused by a novel cTnT gene mutation, Lys273Glu. Two hundred Japanese probands with HC were screened for mutations in the cTnT gene. The Lys273Glu missense mutation was present in 9 persons from 2 unrelated pedigrees. They exhibited different cardiac morphologies: 1 had a dilated cardiomyopathy-like feature, 7 had left ventricular hypertrophy with normal left ventricular systolic function, and the 6 of them had asymmetric septal hypertrophy. A 1-year-old boy was not evaluated with echocardiography. The mean maximum wall thickness was 18.0 +/- 5.5 mm (range 8 to 24). There were 7 histories of sudden death in 1 of the 2 families. The Lys273Glu substitution in the cTnT gene shows a high degree of penetrance (100% in persons aged >20 years), a high incidence of sudden death, and a partial transition from hypertrophic to dilated cardiomyopathy. Because the location of a mutation appears to influence the development of a phenotype, we suggest that the precise definition of the disease-causing mutation can provide important prognostic information about affected members.     

Neutrophil elastase enzymatically antagonizes the in vitro action of G-CSF: implications for the regulation of granulopoiesis

There is evidence that neutrophil production is a balance between the proliferative action of granulocyte-colony-stimulating factor (G-CSF) and a negative feedback from mature neutrophils (the chalone). Two neutrophil serine proteases have been implicated in granulopoietic regulation: pro-proteinase 3 inhibits granulocyte macrophage-colony-forming unit (CFU-GM) growth, and elastase mutations cause cyclic and congenital neutropenia. We further studied the action of the neutrophil serine proteases (proteinase 3, elastase, azurocidin, and cathepsin G) on granulopoiesis in vitro. Elastase inhibited CFU-GM in methylcellulose culture. In serum-free suspension cultures of CD34+ cells, elastase completely abrogated the proliferation induced by G-CSF but not that of GM-CSF or stem cell factor (SCF). The blocking effect of elastase was prevented by inhibition of its enzymatic activity with phenylmethylsulfonyl fluoride (PMSF) or heat treatment. When exposed to enzymatically active elastase, G-CSF, but not GM-CSF or SCF, was rapidly cleaved and rendered inactive. These results support a role for neutrophil elastase in providing negative feedback to granulopoiesis by direct antagonism of G-CSF.     

Recurrent pneumonia due to persistent Chlamydia pneumoniae infection

Two cases of recurrent pneumonia due to Chlamydia pneumoniae are described. C. pneumoniae was continuously detected from the nasopharynx in both patients by the polymerase chain reaction and/or culture even with appropriate antibiotic therapy during the first episode. After eradication of C. pneumoniae with long-term macrolide therapy, the respiratory symptoms of both patients completely disappeared and no relapse was observed. These data indicate that new treatment strategies may be necessary to eradicate the organism in patients prone to persistent infection.     

Trends geriatric disease research evaluated by long-term longitudinal study

The number of patients with geriatric diseases will rapidly increase in our aging society. Geriatric diseases tend to progress chronically and disturb the daily activity of the elderly patients. Care for the elderly patients requires a great deal of manpower. The prevention and treatment of geriatric disease are urgent issues that must be addressed. A comprehensive longitudinal study of aging and geriatric disease was started at the National Institute for Longevity Sciences (NILS) in 1997. The participants of the NILS longitudinal study of aging (NILS-LSA) were 2,267 men and women from a local community population. The participants are examined at the NILS and followed up every two years. An outline of the system and examinations of the NILS-LSA is shown. The latest results from the NILS-LSA research including geriatric disease-related genotypes and risk factors for mild cognitive impairment (MCI) are also presented.     

A case of Bartonella henselae infection from a dog

A 50-year-old male with left cervical lymphadenopathy visited our hospital. Infectious and lymphomatous diseases were suspected in the patient. Since the patient owned a dog, which often licked the patient's face, Bartonella infection was also suspected. Histopathological examination in the lymph node biopsy revealed the epithelioid granuloma, but B. henselae was not detected from the culture of the lymphnode. B. henselae DNA also was not detected from the lymph node. Since the antibody titer (lgG) to B. henselae showed 1:128 by immunofluorescent antibody technique (IFA), he was serdogicalg diagnosed as cat-scratch disease. 'Cat-scratch disease' is named after cat scratch, however we propose 'B. henselae infection' which is more appropriate since other animals could serve as a cause of infection.     

The impact of health problems on depression and activities in middle-aged and older adults: age and social interactions as moderators

In this study, we compared the impact of health problems (HPs) on everyday activities and depressive symptoms between middle-aged and older adults. We also examined what type and source of social interactions moderate the noxious effects of HPs. Longitudinal analyses of data with 1,802 Japanese community-dwelling adults indicated that HPs were significantly related to (a) an increase in depressive symptoms among middle-aged adults and (b) a decline in everyday activities among older adults. The former was buffered by emotional family support, whereas the latter (b) was buffered by instrumental family support and, surprisingly, by negative interactions with family. In contrast, social interactions with other friends and acquaintances did not show any moderating effect.