Intranuclear inclusions of meningioma associated with abnormal cytoskeletal protein expression

We describe a case of meningothelial meningioma with a large number of intranuclear inclusions. Morphologically, these are divided into cytoplasmic inclusions and nuclear vacuoles. The cytoplasmic inclusion has a limiting membrane with cell organelles and filaments. Inclusions of this type are generally eosinophilic, like the cytoplasm. However, there are many inclusions that are more eosinophilic than the cytoplasm or that have a ground-glass appearance. Some of them may contain fine or coarse granules. On the other hand, the nuclear vacuole lacks a limiting membrane and appears empty. In most of the inclusions of this type, there is a faintly basophilic substance in the margin. Generally, the cytoplasmic inclusions are as immunopositive as cytoplasm with vimentin, but some of these cytoplasmic inclusions are more reactive. Under the electron microscope, abnormal aggregation of intermediate filaments is recognized in the cytoplasmic inclusions. It is considered that a strong reaction of cytoplasmic inclusions with vimentin immunostaining is due to abnormal aggregation of intermediate filaments. The present study distinctly demonstrates abnormal localization of intermediate filaments in the cytoplasmic inclusions, and it is suggested that the cytoskeleton participates in the evolution of the cytoplasmic inclusions.     

The Effect of Combination Therapy with Interferon and Cryofiltration on Mesangial Proliferative Glomerulonephritis Originating from Mixed Cryoglobulinemia in Chronic Hepatitis C Virus Infection

Abstract: Cryofiltration, which has developed from double filtration plasmapheresis (DFPP) with a cooling unit, is an on-line technique to remove cryoglobulin. We report on a patient who suffered from progressive edema and renal insufficiency caused by cryoglobulinemic membranoproliferative glomerulonephritis (MPGN), probably due to chronic hepatitis C virus (HCV) infection. To remove cryoglobulins and terminate the HCV infection, we utilized combination therapy with cryofiltration and interferon-α injection with corticosteroids. Interferon-α was capable of decreasing proteinuria but not diminishing cryoglobulin. Additional cryofiltration could remove cryoglobulin to an undetectable level. This combination therapy was partially successful to reduce proteinuria and prevent the progressive deterioration of renal function. The major adverse effects of this therapy were bleeding and myelosuppression. We conclude that this combination therapy may be effective and should be considered as treatment for cryoglobulinemic MPGN.     

Study of the effect of combination therapy of human granulocyte-colony stimulating factor (G-CSF) and amikacin on experimental pyelonephritis induced by Pseudomonas aeruginosa in neutropenic mice]

We reported the prophylactic and therapeutic effect of human granulocyte-colony stimulating factor (G-CSF) on mice with ascending pyelonephritis induced by Pseudomonas aeruginosa (G-group). In the cyclophosphamide-treated neutropenic mice, the prophylactic administration of G-CSF (2 micrograms/day/mouse) yielded a lower incidence of infection than that of saline alone. However, the therapeutic administration of G-CSF (2 micrograms/day/mouse) did not produce decreases of the rate, suggesting that this type of administration had no effect on infection. Thus, we investigated the effect of the combination therapy of G-CSF and Amikacin. In neutropenic mice, the therapeutic administration of G-CSF alone and Amikacin (20 mg/kg) alone did not produce decreases of incidence of infection. But, combination administration of these yielded a lower incidence of infection. These results suggest that synergy of bactericidal effects of neutrophils accelerated by G-CSF with Amikacin, and a combination of these have a therapeutic effect on bacterial infection in neutropenic mice.     

A case of a flare-up of systemic lupus erythematosus and Sjögren’s syndrome manifesting with cholecystitis secondary to pregnancy

a 30-year- old had a 2 year history of systemic lupus erythematosus (SLE) was transferred to our hospital by her gynecologist because of a low-grade fever and dyspnea after delivery. Since a blood culture performed upon admission showed the presence ofBacteroides caccae, she was diagnosed with sepsis. Antibiotic therapy did not resolve her symptoms and she further developed an acute abdomen with marked cholecystitis. This was believed to be due to a flare-up of SLE after the pregnancy, overlapped with Sjögren’s syndrome which was evidenced by sialaden biopsy. She showed a good response to combination therapy with steroids and antibiotics.     

Psychological stress-induced increases in noradrenaline release in rat brain regions are attenuated by diazepam, but not by morphine

By measuring levels of noradrenaline (NA) and its major metabolite, 3-methoxy-4-hydroxyphenylethyleneglycol sulfate (MHPG-SO4) in the hypothalamus, amygdala and locus coeruleus region, we investigated the effects of diazepam 5.0 mg/kg, morphine 6.0 mg/kg, or naloxone at 5.0 or 10 mg/kg injected SC immediately before stress exposure, on increases in NA release caused by psychological stress. Psychological stress, wherein rats were exposed to emotional responses which were displayed by other electrically shocked rats, significantly increased MHPG-SO4 levels in the three brain regions examined and elevated plasma corticosterone levels. Both increases in brain MHPG-SO4 levels and elevations of plasma corticosterone levels induced by stress were attenuated significantly by diazepam but neither by morphine nor by naloxone. MHPG-SO4 levels in the hypothalamus and amygdala in the morphine-stress group were significantly higher than those in the saline-stress group. These findings suggest that psychological stress, in which an emotional factor is predominantly involved, causes increases in NA release in these brain regions examined and that these increases are attenuated only by diazepam, in contrast to the previous report, where increases in brain NA release caused by immobilization stress are attenuated not only by diazepam but also by morphine and are enhanced by naloxone.     

A case of an epithelioid glioblastoma with the BRAF V600E mutation colocalized with BRAF intact low‐grade diffuse astrocytoma

Epithelioid glioblastomas are one of the rarest histological variants of glioblastomas, which are not formally recognized by the World Health Organization (WHO) classification. Epithelioid glioblastomas usually occur as primary lesions, but there have been several reports of secondary epithelioid glioblastomas or epithelioid glioblastomas with pre‐ or co‐existing lesions to date. The serine/threonine‐protein kinase B‐Raf (BRAF) V600E mutation has been found at a high frequency of 54% in epithelioid glioblastomas. We present a case of a 26‐year‐old female patient with an epithelioid glioblastoma with the BRAF V600E mutation in her right frontal lobe. In the present case, a low‐grade diffuse astrocytoma component had colocalized with the epithelioid glioblastoma. The component presented prominent calcification on neuroimages as well as by histology, and low‐grade diffuse astrocytoma was considered to be a precursor lesion of an epithelioid glioblastoma. However, the BRAF V600E mutation was detected only in epithelioid glioblastoma but not in low‐grade diffuse astrocytoma. To the best of our knowledge, this is the first report demonstrating a discrepancy in the BRAF V600E mutation states between epithelioid glioblastoma and colocalized low‐grade astrocytoma.     

Tosulfoxacin treatment ofChlamydia trachomatis infection of the uterine cervix

In vivo efficacy of tosufloxacin (TFLX) for treatment ofChlamydia trachomatis cervical infection in women was evaluated by enzyme immunoassay. The short term (within 31 days of treatment) response rates with a dosage of 150 mg orally 3 times daily were 100% (54/54) with 14 days of treatment and 97% (38/39) with 7 days of treatment. Subjective symptoms such as lower abdominal pain, vaginal discharge, or atypical bleeding were observed in 76 (82%) of the 93 patients. After treatment, symptoms improved in 75 (99%) of 76 patients. Two of 34 patients (5.9%) showed positive results in the long interval tests (1 to 18 months after treatment). Three (2.3%) of 131 patients needed to be changed from TFLX to other drugs due to side effects (eczema, face edema, urticaria). TFLX was effective and patients showed high compliance for treatment of cervicalC. trachomatis infection.     

In vitro antifungal activity of KP-103, a novel triazole derivative, and its therapeutic efficacy against experimental plantar tinea pedis and cutaneous candidiasis in guinea pigs

The in vitro activity of KP-103, a novel triazole derivative, against pathogenic fungi that cause dermatomycoses and its therapeutic efficacy against plantar tinea pedis and cutaneous candidiasis in guinea pigs were investigated. MICs were determined by a broth microdilution method with morpholinepropanesulfonic acid-buffered RPMI 1640 medium for Candida species and with Sabouraud dextrose broth for dermatophytes and by an agar dilution method with medium C for Malassezia furfur. KP-103 was the most active of all the drugs tested against Candida albicans (geometric mean [GM] MIC, 0.002 microg/ml), other Candida species including Candida parapsilosis and Candida glabrata (GM MICs, 0.0039 to 0.0442 microg/ml), and M. furfur (GM MIC, 0.025 microg/ml). KP-103 (1% solution) was highly effective as a treatment for guinea pigs with cutaneous candidiasis and achieved mycological eradication in 8 of the 10 infected animals, whereas none of the imidazoles tested (1% solutions) was effective in even reducing the levels of the infecting fungi. KP-103 was as active as clotrimazole and neticonazole but was less active than lanoconazole and butenafine against Trichophyton rubrum (MIC at which 80% of isolates are inhibited [MIC(80)], 0.125 microg/ml) and Trichophyton mentagrophytes (MIC(80), 0.25 microg/ml). However, KP-103 (1% solution) exerted therapeutic efficacy superior to that of neticonazole and comparable to those of lanoconazole and butenafine, yielding negative cultures for all samples from guinea pigs with plantar tinea pedis tested. This suggests that KP-103 has better pharmacokinetic properties in skin tissue than the reference drugs. Because the in vitro activity of KP-103, unlike those of the reference drugs, against T. mentagrophytes was not affected by hair as a keratinic substance, its excellent therapeutic efficacy seems to be attributable to good retention of its antifungal activity in skin tissue, in addition to its potency.