[The Effect of Intravenous Gamma-globulin Reagents on the Measurement Results of (1➔3)-ß-D-glucan].

Serum (1→3) beta-D-glucan (BG) measurement is a useful test for systemic mycoses, and often used. On the other hand, various factors, including administration of intravenous immunoglobulins (IVIG) may cause false-positives. In the present study, we measured BG concentration of seven IVIG preparations with three lots respectively. BG levels varied with individual IVIG preparations (<3.0 - >300 pg/mL), and contamination from manufacturing processes was suspected. With serum BG concentration of clinical specimens obtained in Niigata University Medical & Dental Hospital, the difference between before and after administration of IVIG were calculated. The false-positive rate of BG due to IVIG administration was 9.8 %, and the positive predective value was reduced to 37.5%. Above all, administration of IVIG can complicate the BG test's interpretation, and caution is required.

[An autopsy case involving severe sepsis due to Capnocytophaga canimorsus infection].

Capnocytophaga canimorsus, a commensal bacterium from the carine mouth, causes septicemia in human beings through bites or scratches. We report a case of a 60-year-old man contracting septicemia due to C. canimorsus infection after a dog bite who died less than 12 hours after admission. We observed neutrophils with intracytoplasmic bacilli in the peripheral blood smear. We discuss clinical presentation and autopsy findings.

Spontaneous resolution of thoracic radiation therapy-induced organizing pneumonia: A case series.

We retrospectively analyzed the data of 9 patients with organizing pneumonia induced by radiation therapy. Radiation therapy had been administered for breast cancer in 8 patients and for lung cancer in 1 patient. Symptoms were detected in 8 patients; however, none of the patients developed hypoxemia or respiratory failure, and the clinical course was good. Steroid therapy was administered to 3 patients; however, all 3 patients developed recurrence. In contrast, none of the 6 patients who received symptomatic treatment developed recurrence. Steroid treatment is often provided for patients with organizing pneumonia; however, the effect of steroid administration on recurrence rate needs to be examined. In addition, none of the patients died and only 1 patient with lung cancer required mechanical ventilation. Therefore, considering the serious side effects of steroid use, initial symptomatic treatment, and not steroid administration, may be best for patients. One exception would be for patients with hypoxemia or those whose symptoms adversely affect the activities of daily living. The incidence of radiation therapy-induced organizing pneumonia in lung cancer patients is higher and its severity is greater than that in breast cancer patients; however, the time to onset may be longer in lung cancer patients. Therefore, more attention should be paid towards the diagnosis and treatment of radiation therapy-induced organizing pneumonia in patients with lung cancer as compared to that in patients with breast cancer.

[Case of central neurosarcoidosis with panhypopituitalism].

A 63-year-old man was admitted because of dizziness, polydipsia, polyuria, and diminished libido. His brain MRI showed swelling of the pituitary gland. Because of panhypopituitarism suggested by hormonal examination, hydrocortisone, desmopressin and levothyroxine sodium were started as hormone replacement therapy. He was given a clinical diagnosis of central neurosarcoidosis with panhypopituitarism because of the presence of an abnormal lung shadow, positive gallium scintigram in bilateral hilar lymph nodes, negative tuberculin skin test, lymphocytosis and a high CD4/8 ratio in bronchoalveolar lavage fluid. After prednisolone therapy, his lung shadow and pituitary swelling reduced significantly. Anti-diuretic hormones and anterior pituitary hormones tended to increase, and his urine volume also decreased. This case suggested that endocrinological abnormalities in central neurosarcoidosis might be improved by prednisolone therapy even if the initiation of treatment is delayed.

PDZ domain-binding motif of human T-cell leukemia virus type 1 Tax oncoprotein is essential for the interleukin 2 independent growth induction of a T-cell line.

BACKGROUND: Human T-cell leukemia virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia (ATL), whereas HTLV type 2 (HTLV-2), is not associated with ATL or any other leukemia. HTLV-1 encodes the transforming gene tax1, whose expression in an interleukin (IL)-2-dependent T-cell line (CTLL-2) induces IL-2-independent growth. RESULTS: In this study, we demonstrated that IL-2-independent growth induction by Tax1 was abrogated by mutations of the PDZ domain-binding motif (PBM) at the Tax1 C-terminus. HTLV-2 Tax2, which shares 75% amino acid identity with Tax1 but does not have a PBM, was not able to induce IL-2-independent growth of CTLL-2. CONCLUSION: Our results suggest that Tax1, through interaction with PDZ domain protein(s) induces IL-2-independent growth, which may be a factor in multi-step leukemogenesis caused by HTLV-1.

Anti-interferon-gamma autoantibody in a patient with disseminated Mycobacterium avium complex.

We report the case of a 44-year-old woman with disseminated Mycobacterium avium complex (MAC) infection involving multiple bone lesions despite a normal healthy status until 6 months previously. Because she was suspected to have acquired immunodeficiency, we tested interferon (IFN)-gamma production by peripheral blood mononuclear cells (PBMC) after phytohemagglutinin (PHA) or anti-CD3 stimulation, and found that these cells produced no, or undetectable, levels of IFN-gamma in the presence of the patient's plasma, but produced nearly normal levels of IFN-gamma in the presence of healthy donor plasma. Since the IgG fraction of the patient's plasma was capable of blocking in vitro responses to IFN-gamma, the cause of disseminated MAC infection in this case appeared to be anti-IFN-gamma autoantibodies. To reduce the titer of anti-IFN-gamma autoantibodies, the patient received intravenous immunoglobulin (IVIG). However, titer of autoantibodies changed little compared to that before IVIG administration. According to our literature search, this is only the second case of disseminated MAC infection associated with anti-IFN-gamma autoantibodies in Japan.

Cooperation of NF-kappaB2/p100 activation and the PDZ domain binding motif signal in human T-cell leukemia virus type 1 (HTLV-1) Tax1 but not HTLV-2 Tax2 is crucial for interleukin-2-independent growth transformation of a T-cell line.

Human T-cell leukemia virus type 1 (HTLV-1) but not HTLV-2 is associated with adult T-cell leukemia, and the distinct pathogenicity of these two closely related viruses is thought to stem from the distinct biological functions of the respective transforming proteins, HTLV-1 Tax1 and HTLV-2 Tax2. In this study, we demonstrate that Tax1 but not Tax2 interacts with NF-kappaB2/p100 and activates it by inducing the cleavage of p100 into the active transcription factor p52. Using RNA interference methods, we further show that NF-kappaB2/p100 is required for the transformation induced by Tax1, as determined by the ability to convert a T-cell line (CTLL-2) from interleukin-2 (IL-2)-dependent to -independent growth. While Tax2 shows a reduced transforming activity relative to Tax1, Tax2 fused with a PDZ domain binding motif (PBM) present only in Tax1 shows transforming activity equivalent to that of Tax1 in CTLL-2 cells expressing an inducer of p52 processing. These results reveal that the activation of NF-kappaB2/p100 plays a crucial role in the Tax1-mediated transformation of T cells and that NF-kappaB2/p100 activation and PBM function are both responsible for the augmented transforming activity of Tax1 relative to Tax2, thus suggesting that these Tax1-specific functions play crucial roles in HTLV-1 leukemogenesis.