Multi-center analysis of calcinosis in children with juvenile dermatomyositis]

OBJECTIVES: To reveal the frequency and the clinical characteristics of dystrophic calcification that occurs in children with juvenile dermatomyositis, multi-center analysis was constructed. METHOD: Fifty children with JDM were enrolled, and 14 of them (28.0%) were complicated with calcinosis. Clinical symptoms and laboratory tests at onset, initial therapy and disease course were compared in children with and without calcinosis. RESULTS: The mean age of the onset of calcinosis was 4.78 +/- 3.33 years, and it was younger than those of children without calcinosis (8.66 +/- 3.85 years) (P = 0.0017). No differences of clinical manifestation except Gower's sign were observed. The frequency of positive anti-nuclear antibody was 7.1% in children with calcinosis and 52.9% without calcinosis (P = 0.0112). The initial therapy of methylprednisolon pulses gave no effects on prognosis of calcium deposition. The calcinosis appeared in 1.56 +/- 1.91 year after the onset of the disease. The various types of calcium deposition including large tumorous clumps, subcutaneous plaques or nodules, sheet-type calcification were deserved. They appeared over knee joints (64.3%), elbow joint (64.3%), and hip processes (50.0%). Calcinosis affecting the subcutaneous tissues frequently resulted in painful superficial ulceration of the overlying skin (42.9%), local infection (50.0%), and limitation of joint movement (14.3%). Although aluminum phosphate was effective in 2 children among 7, no other effective treatment was recommended. In 5 cases, surgical removal of tumorous clumps was operated. Thus, juvenile dermatomyositis is frequently complicated with calcinosis. This type of calcinosis was found to be unlikely to resolve completely, and resulted in severe disability in children.     

Correlation between inflammatory cellular responses and chemotactic activity in bronchoalveolar lavage fluid following intratracheal instillation of nickel sulfate in rats

In a preceding study, we reported that the numbers of macrophages and polymorphonuclear leukocytes (PMN) were increased in bronchoalveolar lavage fluid (BALF) following the intratracheal instillation of nickel sulfate (NiSO₄) in rats. In the present study, BALF chemotactic activities for both macrophages and PMN were measured to investigate if the increases of these inflammatory cells in BALF depend on increases in chemotactic activities in epithelial lining fluid (ELF) of the lung. Both the number of PMN and the PMN chemotactic activity peaked at 2 days post-instillation and they were significantly correlated. However, the PMN chemotactic activity was inversely correlated with concentration of leukotriene B₄ (LTB₄), a well-known chemotaxin. Although PMN were not observed in control BALF, LTB₄ concentration in the control ELF (ca. 5×10^–7 M) was estimated to have a potential to attract PMN chemotactically through a membrane in in vitro migration assay. These results suggest that the presence of LTB₄ in ELF itself does not trigger transpulmonary PMN infiltration. The rat BALF were fractionated by high performance liquid chromatography (HPLC), and PMN chemotactic activity of each fraction was measured. The elution profiles of PMN chemotactic activity showed that there were at least two different chemotaxins in BALF obtained from the NiSO₄-exposed rats. Macrophage chemotactic activity in BALF also peaked at 2 days post-instillation. However, the number of macrophages was not significantly correlated with the chemotactic activity for macrophage in BALF. The HPLC study showed that the macrophage chemotactic substance in the BALF obtained from NiSO₄-exposed rats was different from complement fragment (C5a) and its MW was estimated to be 10 – 12 kD. Received: 1 December 1993/Accepted: 16 March 1994     

Renovascular hypertension: a unique cause of unilateral focal segmental glomerulosclerosis.

A 48-year-old man presented with malignant hypertension and massive proteinuria. Renal angiography showed complete obstruction of the left renal artery and 99mTc-mercaptoacetylglycine (MAG3) renography showed a nonfunctioning left kidney. Percutaneous transluminal renal angioplasty of the left renal artery was unsuccessful; hence, the patient underwent left nephrectomy because of uncontrolled hypertension and proteinuria. Histological examination of a right kidney specimen revealed lesions of focal segmental glomerulosclerosis with benign nephrosclerosis. In contrast, histology of the left kidney showed typical ischemic kidney with hypertrophy of arteriolar smooth muscle cells. The patient responded favorably to the nephrectomy, as his blood pressure and urinary protein dramatically decreased with no antihypertensive medication. This case illustrates the heterogeneous effect of the renin-angiotensin system on either kidney in patients with renovascular hypertension due to unilateral renal artery stenosis.     

Improved expression of gamma-aminobutyric acid receptor in mice with cerebral infarct and transplanted bone marrow stromal cells: an autoradiographic and histologic analysis.

Recent studies have indicated that bone marrow stromal cells (BMSC) have the potential to improve neurologic function when transplanted into animal models of central nervous system disorders. However, how the transplanted BMSC restore the lost neurologic function is not clear. In the present study, therefore, we aimed to elucidate whether BMSC express the neuron-specific gamma-aminobutyric acid (GABA) receptor when transplanted into brain that has been subjected to cerebral infarction. METHODS: The BMSC were harvested from green fluorescent protein-transgenic mice and were cultured. The mice were subjected to permanent middle cerebral artery occlusion. The BMSC or vehicle was transplanted into the ipsilateral striatum 7 d after the insult. Using autoradiography and fluorescence immunohistochemistry, we evaluated the binding of 125I-iomazenil and the expression of GABA receptor protein in and around the cerebral infarct 4 wk after transplantation. RESULTS: Binding of 125I-iomazenil was significantly higher in the periinfarct neocortex in the BMSC-transplanted animals than in the vehicle-transplanted animals. Likewise, the number of the GABAA receptor-positive cells was significantly higher in the periinfarct neocortex in the BMSC-transplanted animals than in the vehicle-transplanted animals. A certain subpopulation of the transplanted BMSC expressed a neuron-specific marker, microtubule-associated protein 2, and the marker protein specific for GABAA receptor in the periinfarct area. CONCLUSION: These findings suggest that BMSC may contribute to neural tissue regeneration through migrating toward the periinfarct area and acquiring the neuron-specific receptor function.     

Evaluation of anti-parvovirus B19 activity in sera by assay using quantitative polymerase chain reaction

Human parvovirus B19 (B19) infects cells of erythroid lineage. Production of neutralizing antibodies (Abs) is indispensable for recovery from B19-related disease state. In this study, we used a convenient method to measure neutralizing activities in human sera by using a real-time quantitative PCR based assay. Erythroid cell line KU812Ep6 was incubated with test sera before infection with B19 virus. The copy number of B19-DNA in cultures was decreased in the presence of the sera from patients who recovered from acute B19 infection, whereas no decrease in B19-DNA was in cultures incubated with sera from healthy volunteers who had no B19 infection. The decrease in B19-DNA copy number was calculated and the inhibition percentage was expressed as neutralizing activity to B19. A clinical study showed that the levels of neutralizing ability were high in patients who recovered soon after acute B19 infection, but were low in some patients with a prolonged clinical course for recovery from B19 infection. This method is simple and convenient compared with methods described previously, showing its usefulness to evaluate the neutralizing activity to B19.     

Rapid Detection of Species of the Opportunistic Yeast Trichosporon by PCR

Trichosporon species are opportunistic pathogens, associated with a high mortality rate in immunocompromised patients. Oligonucleotide primers were used to amplify a 170-bp fragment of small-subunit ribosomal DNA of all species in the genus Trichosporon by PCR. The primers amplify DNAs of all species in the genus Trichosporon, including six causative agents of trichosporonosis. DNAs of other medically important yeasts, such as Candida albicans and Cryptococcus neoformans, are not amplified by this detection system.     

An improved method for recovery of F-defective Sendai virus expressing foreign genes from cloned cDNA

An improved system is described to recover non-transmissible Sendai virus that lack the envelope fusion (F) gene from cloned cDNA. The system (1) used plasmids that expressed the F and the HN viral envelope proteins, as well as the plasmids that expressed the viral NP, P, and L proteins as helper plasmids for recovery, and (2) overlaid packaging cells that expressed the F protein. With this improved system, we have succeeded in recovery of F-defective Sendai virus expressing two foreign proteins, and expression vectors that do not contain the EGFP reporter gene. This system may provide the basis for constructing recombinant F-defective Sendai virus for preventing and treating human diseases in the form of vaccines and vectors for gene therapy.