CD56+ B-cell Neurolymphomatosis in a Cat.

A 16-year-old male Russian blue cat was presented with acute onset of paraparesis of the forelimbs that progressed to tetraparesis. Neurological examination revealed non-ambulatory tetraparesis with decreased postural reactions in all four limbs. Magnetic resonance imaging revealed multifocal nerve root swelling on the right at C6/C7 and C7/T1, while ultrasonography demonstrated swelling of the right brachial plexus. To understand the cause of the nerve swelling, the right musculocutaneous nerve arising from the brachial plexus and the pectoralis muscle were biopsied. Histologically, there was evidence of neurolymphomatosis (neurotropic lymphoma) with Wallerian degeneration and denervation atrophy of myofibres. The neoplastic lymphoid cells expressed CD79a, CD20 and CD56. Based on these findings, a diagnosis of B-cell neurolymphomatosis was made. Expression of CD56, synonymous with neural cell adhesion molecule, is rare in B-cell lymphomas and has not been reported in feline B-cell lymphomas or feline neurolymphomatosis. CD56 expression was suspected to have played an important role in neurotropism of the neoplastic cells in this case.

Diffuse-type Gastric Mucinous and Signet Ring Cell Adenocarcinoma in a Captive California King Snake (Lampropeltis getula californiae).

An adult female California king snake (Lampropeltis getula californiae) housed in Taipei Zoo was presented with a 2-week history of anorexia, fatigue and abdominal swelling. Exploratory laparotomy revealed a gastric mass with two circular perforations and multiple mottled white to beige protuberances along the mucosal surface. Histologically, the gastric mass showed an invasive, transmural growth of epithelial cells arranged in nests, lobules, acini and sheets in the mucosa and submucosa that progressively transformed into signet ring cells in the muscularis externa and subserosa. All of the neoplastic cells expressed pan-cytokeratin immunohistochemically. Based on the World Health Organization histological criteria, a diagnosis of diffuse-type gastric mucinous and signet ring cell adenocarcinoma was made.

Simultaneous induction of HSP70 expression, and degranulation, in IgE/Ag-stimulated or extracellular HSP70-stimulated mast cells.

BACKGROUND: In mast cells, induction of HSP70 expression during antigen stimulation has not been reported. METHODS: Mouse bone marrow-derived mast cells (BMMC) were stimulated with IgE/Ag or HSP70. Induction of HSP70 expression and signaling protein phosphorylation were evaluated by immunoblotting. RESULTS: HSP70 expression is induced in BMMC at an early stage of IgE/Ag-dependent stimulation, some of which is released from the cells in a granule-associated form. Induction of HSP70 expression was also observed with an IgE/Ag-stimulated human basophilic cell line, indicating that the phenomenon is not restricted to mouse BMMC. The induction of HSP70 expression, and its release, followed a similar time course to that of degranulation. Released HSP70 seems to be responsible for degranulation and production of eicosanoids, at least in part, because a neutralizing anti-HSP70 antibody mitigated these activities and because exogenous HSP70 not only induced immediate degranulation followed by autocrine HSP70 expression but also enhanced degranulation in IgE/Ag-stimulated BMMC. Extracellular HSP70 was found to induce phosphorylation of linker for activation of T cells (LAT) and a series of downstream signaling molecules in BMMC. We further found that Fyn, Lyn, and spleen tyrosine kinase (Syk), which are known to concern LAT phosphorylation in IgE/Ag-stimulated BMMC, were not phosphorylated in HSP70-stimulated BMMC, whereas lymphocyte-specific protein tyrosine kinase (Lck) was phosphorylated. CONCLUSION: FcεRI stimulation in BMMC and basophils induces HSP70 expression and its release. Extracellular HSP70 induces degranulation and mediator release via phosphorylation of LAT.

[Inhibiting the pro-tumor and transcription factor FACT: Mechanisms].

Conventional antitumor therapy is often complicated by the emergence of the so-called cancer stem cells (CSCs), which are characterized by low metabolic rates and high resistance to almost all existing therapies. Many problems of clinical oncology and a poor efficacy of current treatments in particular are ascribed to CSCs. Therefore, it is important to develop new compounds capable of eliminating both rapidly proliferating tumor cells and standard treatment-resistant CSCs. Curaxins have been demonstrated to manifest various types of antitumor activity. Curaxins simultaneously affect at least three key molecular cascades involved in tumor development, including the p53, NF-κB, and HSF1 metabolic pathways. In addition, studies of some curaxins indicate that they can inhibit the transcriptional induction of the genes for matrix metalloproteinases 1 and 8 (MMP1 and MMP8); the PI3K/AKT/mTOR signaling cascades; cIAP-1 (apoptosis protein 1) inhibitor activity; topoisomerase II; and a number of oncogenes, such as c-MYC and others. In vivo experiments have shown that the CSC population increases on gemcitabine monotherapy and is reduced on treatment with curaxin CBL0137. The data support the prospective use of FACT inhibitors as new anticancer drugs with multiple effects on cell metabolism.

Betulinic acid enhances TGF-ß signaling by altering TGF-ß receptors partitioning between lipid-raft/caveolae and non-caveolae membrane microdomains in mink lung epithelial cells.

BACKGROUND: TGF-ß is a key modulator in the regulation of cell proliferation and migration, and is also involved in the process of cancer development and progression. Previous studies have indicated that TGF-ß responsiveness is determined by TGF-ß receptor partitioning between lipid raft/caveolae-mediated and clathrin-mediated endocytosis. Lipid raft/caveolae-mediated endocytosis facilitates TGF-ß degradation and thus suppressing TGF-ß responsiveness. By contrast, clathrin-mediated endocytosis results in Smad2/3-dependent endosomal signaling, thereby promoting TGF-ß responsiveness. Because betulinic acid shares a similar chemical structure with cholesterol and has been reported to insert into the plasma membrane, we speculate that betulinic acid changes the fluidity of the plasma membrane and modulates the signaling pathway associated with membrane microdomains. We propose that betulinic acid modulates TGF-ß responsiveness by changing the partitioning of TGF-ß receptor between lipid-raft/caveolae and non-caveolae microdomain on plasma membrane. METHODS: We employed sucrose-density gradient ultracentrifugation and confocal microscopy to determine membrane localization of TGF-ß receptors and used a luciferase assay to examine the effects of betulinic acid in TGF-ß-stimulated promoter activation. In addition, we perform western blotting to test TGF-ß-induced Smad2 phosphorylation and fibronectin production. RESULTS AND CONCLUSIONS: Betulinic acid induces translocation of TGF-ß receptors from lipid raft/caveolae to non-caveolae microdomains without changing total level of TGF-ß receptors. The betulinic acid-induced TGF-ß receptors translocation is rapid and correlate with the TGF-ß-induced PAI-1 reporter gene activation and growth inhibition in Mv1Lu cells.

NecroX-5 suppresses IgE/Ag-stimulated anaphylaxis and mast cell activation by regulating the SHP-1-Syk signaling module.

BACKGROUND: IgE/Ag-stimulated mast cells release various pro-allergic inflammatory mediators, including histamine, eicosanoids, and pro-inflammatory cytokines. NecroX-5, a cell permeable necrosis inhibitor, showed cytoprotective effects in both in vitro and in vivo models. However, the anti-allergic effect of NecroX-5 has not yet been investigated. The aims of this study were to evaluate the anti-allergic activity of NecroX-5 in vivo and to investigate the underlying mechanism in vitro. METHODS: The anti-allergic activity of NecroX-5 was evaluated in vitro using bone marrow-derived mast cells (BMMCs) and IgE receptor-bearing RBL-2H3 or KU812 cells and in vivo using a mouse model of passive anaphylaxis. The levels of histamine, eicosanoids (PGD2 and LTC4 ), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were measured using enzyme immunoassay kits. The mechanism underlying the action of NecroX-5 was investigated using immunoblotting, immunoprecipitation, and gene knockdown techniques. RESULTS: NecroX-5 markedly inhibited mast cell degranulation and the synthesis of eicosanoids, TNF-α, and IL-6 by suppressing the activation of Syk, LAT, phospholipase Cγ1, MAP kinases, the Akt/NF-κB pathway, and intracellular Ca(2+) mobilization via the activation of phosphatase SHP-1. Oral administration of NecroX-5 effectively suppressed mast cell-dependent passive cutaneous and systemic anaphylactic reactions in a dose-dependent manner. CONCLUSIONS: NecroX-5 might be a potential candidate for the development of a novel anti-allergic agent that suppresses IgE-dependent mast cells signaling.

BCAS2 promotes prostate cancer cells proliferation by enhancing AR mRNA transcription and protein stability.

BACKGROUND: We showed previously that breast carcinoma amplified sequence 2 (BCAS2) functions as a negative regulator of p53. We also found that BCAS2 is a potential AR-associated protein. AR is essential for the growth and survival of prostate carcinoma. Therefore we characterised the correlation between BCAS2 and AR. METHODS: Protein interactions were examined by GST pull-down assay and co-immunoprecipitation. Clinical prostate cancer (PCa) specimens were evaluated by immunohistochemical assay. AR transcriptional activity and LNCaP cell growth were assessed by luciferase assay and MTT assay, respectively. RESULTS: BCAS2 expression was significantly increased in PCa. BCAS2 stabilised AR protein through both hormone-dependent and -independent manners. There are at least two mechanisms for BCAS2-mediated AR protein upregulation: One is p53-dependent. The p53 is suppressed by BCAS2 that results in increasing AR mRNA and protein expression. The other is via p53-independent inhibition of proteasome degradation. As BCAS2 can form a complex with AR and HSP90, it may function with HSP90 to stabilise AR protein from being degraded by proteasome. CONCLUSIONS: In this study, we show that BCAS2 is a novel AR-interacting protein and characterise the correlation between BCAS2 and PCa. Thus we propose that BCAS2 could be a diagnostic marker and therapeutic target for PCa.

Simultaneous presentation of acute disseminated encephalomyelitis (ADEM) and systemic lupus erythematosus (SLE) after enteroviral infection: can ADEM present as the first manifestation of SLE?

Central Nervous System (CNS) involvement of Systemic Lupus Erythematosus (SLE) includes a broad range of neuropsychiatric syndromes. Acute Disseminated Encephalomyelitis (ADEM) is a demyelinating CNS disorder characterized by encephalopathy and multifocal lesions predominantly involving the white matter on brain magnetic resonance imaging. ADEM associated with SLE has been only rarely reported. We report an unusual case of a 17-year-old girl who developed ADEM after enteroviral infection as the first manifestation of SLE. The authors emphasize that the patient's illness was preceded by enteroviral infection and that ADEM occurred before any other symptoms of SLE, which makes this case unique.

A tryptophan metabolite, kynurenine, promotes mast cell activation through aryl hydrocarbon receptor.

BACKGROUND: Tryptophan metabolites have been suggested to play a role in immune modulation, wherein those have recently been shown to be endogenous ligands of aryl hydrocarbon receptor (AhR; a unique cellular chemical sensor). However, the involvement of tryptophan metabolites and AhR in modulating mast cell function remains to be fully defined. We therefore investigated that the functional impacts of tryptophan metabolites on human and mouse mast cell responses in vitro and their functional importance in vivo. METHODS: Three tryptophan metabolites, kynurenine (KYN), kynurenic acid (KA) and quinolinic acid (QA), were examined in terms of their effect on IgE-mediated responses in mouse bone marrow-derived mast cells (BMMCs) and in human peripheral blood-derived cultured mast cells (HCMCs) and on in vivo anaphylactic responses. For evaluation of AhR involvement, we examined the responses of mast cells from AhR-null or AhR-wild-type mice with the use of a known AhR antagonist, CH223191. RESULTS: Kynurenine, but not KA and QA, enhanced IgE-mediated responses, including degranulation, LTC4 release, and IL-13 production in BMMCs through the activation of PLCγ1, Akt, MAPK p38, and the increase of intracellular calcium. KYN also enhanced cutaneous anaphylaxis in vivo. These enhancing effects of KYN were not observed in AhR-deficient BMMCs and could be inhibited by CH223191 in BMMCs. Further, KYN had similar enhancing effects on HCMCs, which were inhibited by CH223191. CONCLUSION: The AhR-KYN axis is potentially important in modulating mast cell responses and represents an example of AhR's critical involvement in the regulation of allergic responses.

Prevalence of haematuria positively associated with urine albumin excretion in Type 2 diabetes.

AIMS: Some guidelines or studies consider haematuria an indication for renal biopsy or a potential cause of albuminuria that precludes accurate assessment of urinary albumin excretion. This study examined the justification of excluding haematuria in interpreting urinary albumin excretion in patients with Type 2 diabetes and its associations with other diabetes-related variables. METHODS: Between May and November 2008, patients with Type 2 diabetes at a single centre with data on urinary albumin excretion and urinalysis in the same urine sample were recruited. Urinary albumin excretion was determined by urine albumin/creatinine ratio in spot urine. Diagnosis of haematuria was made by positive urine occult blood from 1+ to 4+ and/or presence of more than nine red blood cells/ml in urinalysis. Demographic, anthropometric, clinical and laboratory variables and diabetes-associated complications were analysed. RESULTS: In total, 743 patients were enrolled. Prevalence of haematuria among patients with normoalbuminuria, microalbuminuria, or macroalbuminuria was 8.7% (n = 13), 16.1% (n = 67) and 35.8% (n = 64), respectively. Urine albumin/creatinine ratio was significantly higher, while macroalbuminuria was more common in patients with haematuria (n = 144) than in those without (n = 599). Multiple regression analysis identified urine albumin/creatinine ratio (odds ratio 1.33, P = 0.01) and macroalbuminuria (odds ratio 2.66, P = 0.01) as the only independent predictors of haematuria. Moreover, urine albumin/creatinine ratio was an independent predictor of haematuria in the macroalbuminuria subgroup (odds ratio 1.30, P = 0.04). CONCLUSIONS: Increased urine albumin/creatinine ratio and macroalbuminuria were the only independent predictors of haematuria in patients with Type 2 diabetes, raising questions on the justifications of excluding haematuria in interpreting urinary albumin excretion in patients with Type 2 diabetes and including haematuria as an indication for renal biopsy in those with macroalbuminuria.

CT features of lobular capillary hemangioma of the nasal cavity.

BACKGROUND AND PURPOSE: Lobular capillary hemangioma is a benign capillary proliferation of unknown etiology. To our knowledge, no comprehensive review of imaging findings of LCHNC has been presented. Thus, we investigated characteristic CT features of LCHNC. MATERIALS AND METHODS: This retrospective study included 6 patients (2 men and 4 women; age range, 30-65 years; mean age, 49.2 years) with histologically proved LCHNC. We evaluated the size, site of origin, attenuation on NECT, degree and pattern of enhancement, and bony changes. RESULTS: The LCHNC lesion was 13.0-45.0 mm (average, 25.0 mm) in diameter. These lesions arose from the inferior turbinate in 5 (83.3%) patients and the anterior nasal septum in 1 (16.7%). Compared with the masticator muscles, the LCHNC lesion was hypoattenuating in 2 (33.3%) and isoattenuating on NECT in 4 (66.7%) patients. In 5 (83.3%) patients, the LCHNC lesion consisted of 2 distinct areas on CECT: a lobular intensely enhancing mass and an iso- or hypoattenuating cap of variable thickness around the intensely enhancing mass. Bony changes included erosion in 3 (50.0%) and displacement in 2 (33.3%) patients. CONCLUSIONS: CT features of LCHNC consist of an intensely enhancing mass and an iso- or hypoattenuating cap on CECT. The inferior turbinate seems to be a common site of origin, and bony changes are not uncommon features of LCHNC. CT is useful not only in identifying the site of origin and assessing the extent but also in suggesting the nature of LCHNC.

Regulation of cytokine expression in human plasmacytoid dendritic cells by prostaglandin I2 analogues.

Plasmacytoid dendritic cells (pDCs) are critical in controlling adaptive immunity, but the mechanisms governing cytokine expression remain incompletely defined. Analogues of prostaglandin (PG)I(2), such as iloprost, can modulate functions of myeloid dendritic cells, but their involvement in the regulation of human pDCs remains unknown. To this end, the regulatory role of PGI(2) analogues on cytokine expression in pDCs was investigated. Circulating pDCs were magnetically sorted with BDCA-4 cell isolation kits from human peripheral blood mononuclear cells and treated with varying concentrations of iloprost with or without the addition of Toll-like receptor agonists, or an I prostanoid (IP) receptor antagonist, CAY10449. The levels of tumour necrosis factor (TNF)-alpha, interferon (IFN)-alpha and interleukin (IL)-10 were measured by ELISA. Iloprost induced IL-10 expression, but suppressed CpG oligodeoxynucleotide- (or imiquimod-) induced TNF-alpha and IFN-alpha production in pDCs. This effect was reversed by the addition of CAY10449. Forskolin, a cyclic adenosine monophosphate activator, conferred a similar modulating effect to that noted in iloprost-treated pDCs, although a higher concentration of forskolin was required to exert the same effect. Iloprost enhanced interleukin-10 and suppressed Toll-like receptor-mediated tumour necrosis factor-alpha and interferon-alpha production of human plasmacytoid dendritic cells via the I prostanoid receptor and, in part, the cyclic adenosine monophosphate pathway.

Complications impaired endothelial progenitor cell function in Type 2 diabetic patients with or without critical leg ischaemia: implication for impaired neovascularization in diabetes.

AIMS: This study tested the hypothesis that migratory function of endothelial progenitor cells (EPCs) is impaired in Type 2 diabetic patients with or without critical leg ischaemia. METHODS: Seventy-four patients were classified into four groups: Type 2 diabetic (n = 21) and non-diabetic patients (n = 10) with critical leg ischaemia and Type 2 diabetic patients without lower extremity vascular disease (n = 30) and healthy subjects (n = 13). The number and functional activity of circulating and cultured EPCs were determined. RESULTS: The migratory function of cultured EPCs was significantly impaired in diabetic patients without (median, 48, interquartile range, 46, 49 count/view/well) and with (median, 51, interquartile range, 46, 60 count/view/well) critical leg ischaemia and non-diabetic patients with critical leg ischaemia (median, 49, interquartile range, 47, 55 count/view/well) compared with healthy subjects (median, 63, interquartile range, 57, 65 count/view/well) (P < 0.0001). The number of circulating EPCs was lower in Type 2 diabetic patients without lower extremity vascular disease (median, 3500, interquartile range, 1600, 6600/10(6) cytometric events) than Type 2 diabetic patients with critical leg ischaemia (median, 5300, interquartile range, 2400, 11,100/10(6) cytometric events), non-diabetic patients with critical leg ischaemia (median, 5550, interquartile range, 2000, 32,100/10(6) cytometric events) and healthy subjects (median, 5400, interquartile range, 2700, 8700/10(6) cytometric events) (P = 0.413). CONCLUSIONS: The migratory function of EPCs is impaired in patients with Type 2 diabetes, even in those without critical leg ischaemia. These findings present an important new insight into the pathogenesis of impaired neovascularization and critical limb ischaemia in diabetic patients and provide avenues of future clinical study.

Bilateral aldosterone-producing adenomas: differentiation from bilateral adrenal hyperplasia.

BACKGROUND: Primary aldosteronism (PA) is a common curable disease of secondary hypertension. Most such patients have either idiopathic bilateral adrenal hyperplasia (BAH) or unilateral aldosterone-producing adenoma (APA). Bilateral APAs are reportedly extremely rare. AIM: To compare the distinctive characteristics, clinical course, and outcomes of bilateral APA vs. BAH. DESIGN: Retrospective record review. METHODS: From July 1994 to Jan 2007, 190 patients diagnosed with PA underwent surgical intervention at our hospital. Bilateral APA was diagnosed in 7/164 patients with histologically-proven APA. Twenty-one patients diagnosed as BAH, and 21 randomly selected of unilateral APA patients, matched by age and sex served as controls. RESULTS: Patients with bilateral APA had similar blood pressure, arterial blood gas analysis, spot urinary potassium to creatinine ratio and clinical symptoms to those with BAH, but lower serum potassium levels (p = 0.027), lower plasma renin activity (p = 0.037), and higher plasma aldosterone concentrations (p = 0.029). Aldosterone-renin ratio (ARR) after administration of 50 mg captopril was higher in bilateral APA than in BAH patients (p = 0.023), but not different between unilateral APA and BAH (p = 0.218). A cut-off of ARR >100 ng/dl per ng/ml/h and plasma aldosterone >20 ng/dl after captopril significantly differentiated bilateral APA from BAH. Bilateral subtotal adrenalectomy normalized blood pressure and biochemistry in all patients with bilateral APA. DISCUSSION: Bilateral APA, presenting simultaneously or sequentially, may not be a rare disease, accounting for 4.3% of APA in this sample. The clinical presentations of bilateral functional adenoma are not different from BAH, but patients with low serum potassium and ARR >100 after captopril should be carefully evaluated for bilateral adenoma.

Urinary cell-free DNA as a potential tumor marker for bladder cancer.

The objective was to assess the possibility of measuring urine creatinine (UCr)-adjusted urinary cell-free (ucf) DNA concentration as a noninvasive screening tool for bladder cancer. Using PicoGreen-based detection, the ucf-DNA/UCr concentration was quantified in urine supernatant specimens from 46 bladder cancer patients and 98 controls and compared to 400-bp real-time PCR-based detection, which detected the amplification of 400-bp beta-actin (named 400-bp ucf-DNA/UCr). The mean concentrations for both PicoGreen and 400-bp ucf-DNA (ng/mL)/UCr (mg/dL) were significantly higher in bladder cancer patients than in controls: 15.28 vs 6.68 (p<0.001, t-test) and 14.98 vs 1.07 (p<0.001), respectively. Among different stages and grades, no significant difference was found between these two methods. The areas under the ROC curves of PicoGreen and 400-bp ucf-DNA/UCr were 0.571 (95% confidence interval, 0.451-0.692) and 0.805 (95% confidence interval, 0.713-0.896), respectively. In 400-bp ucf-DNA/UCr, the best sensitivity and specificity were 86.1% and 72.0% at the cutoff value of 0.0645. These data indicated that 400-bp ucf-DNA/UCr is more reliable for bladder cancer detection than PicoGreen. In conclusion, our results suggest that ucf-DNA/UCr can be used as a potential tumor marker for bladder cancer, especially for detecting longer DNA fragments.

Clinical relevance of intracranial arterial stenoses in tuberculous and cryptococcal meningitis.

OBJECTIVES: Tuberculous and cryptococcal meningitis are two of the most common types of chronic meningitis. The study was performed to assess whether the occurrence of intracranial arterial stenosis is a risk factor for poor outcome in tuberculous and cryptococcal meningitis. METHODS: The clinical relevance of intracranial arterial stenoses in tuberculous and cryptococcal meningitis was studied using transcranial color-coded sonography (TCCS) and magnetic resonance angiography (MRA) over the period of 1 year (2003). A comparison was made between patients with and those without intracranial arterial stenoses during hospitalization. FINDINGS: There were 12 males and three females. Four patients (27%, 4/15) exhibited a stenosis of at least one cerebral artery, of which three had bilateral middle cerebral artery (MCA) stenosis and one had unilateral MCA stenoses. The stenoses were demonstrable during the whole observation period. After 6 months of follow-up, fatality rate was 50% (2/4) in those with intracranial arterial stenosis and 9% (1/11) in those without. Risk of poor outcome at a 6-month endpoint had an odds ratio of 5.3 for patients with intracranial arterial stenoses than those without (reference group). CONCLUSIONS: Intracranial arterial stenoses imply danger of cerebrovascular complications for the treatment of chronic meningitis during hospitalization. This study demonstrates that the frequency of intracranial stenosis in patients affected by chronic meningitis is high (27%) and it may be associated with poorer outcomes.

Time course of cerebral hemodynamics in cryptococcal meningitis in HIV-negative adults.

To evaluate the cerebral hemodynamics in cryptococcal meningitis (CM) patients using non-invasive studies. Serial trans-cranial color-coded sonography (TCCS) and magnetic resonance angiography (MRA) studies were performed to measure the cerebral vasculopathy of 12 HIV-negative CM patients. With TCCS, 8 of the 22 middle cerebral arteries (MCAs) showed stenotic velocities, whereas the time-mean velocity (V(mean)) of the 20 anterior cerebral arteries (ACAs), 22 posterior cerebral arteries (PCAs), and 12 basilar arteries (BAs) did not. In total, five patients had stenotic velocities, three of whom had bilateral M1 stenosis (<50%), whilst two had unilateral M1 stenosis (<50%). The V(mean) of MCA increased from day 1 to day 35 and substantially decreased thereafter. The mean Pulsatility Index (PI) in the studied vessels was higher during the study period. A mismatch of the findings between TCCS and MRA studies were also demonstrated. There was a high incidence and a longer time-period of disturbed cerebral hemodynamics during the clinical course of CM. However, because of the limited case numbers for this study, further large-scale studies are needed to delineate the clinical characteristics and therapeutic influence of cerebrovascular insults in HIV-negative CM patients.

Vaccine-associated rhabdomyosarcoma with spinal epidural invasion and pulmonary metastasis in a cat.

A 7-year-old, female, domestic medium-haired cat had a recurrent deep dermal mass in the interscapular region after initial surgical removal 3 months earlier. The cat had received a killed rabies vaccine and a five-in-one vaccine in the same area about 2 months prior to the first surgery. The relapsed mass was diagnosed as vaccine-associated sarcoma. The cat was euthanized 2 months later because of hind limb paralysis. At necropsy, multiple, poorly demarcated, nodular masses were seen in the muscles around the shoulders, neck, and thoracic vertebrae. Pulmonary metastasis and spinal epidural invasion at T1-T3 with regional cord compression and malacia were observed. Microscopically, the masses consisted of interwoven bundles of spindle cells with prominent multinucleated giant cell formation. The neoplastic cells stained strongly positive for myoglobin, and moderately but variably positive for vimentin, desmin, and alpha- smooth muscle actin. Phosphotungstic acid-hematoxylin staining revealed cytoplasmic striations in scattered tumor cells. The tumor was considered a vaccine-associated rhabdomyosarcoma.

The prognosis of hearing impairment complicating HIV-negative cryptococcal meningitis.

Eight patients who had sensorineural hearing loss (SNHL) associated with cryptococcal meningitis were studied. After a minimum 3-year follow-up, one had died. Among the seven survivors, three had improved, two stabilized, and two progressed. Predictive factors included visual disturbance, meningeal enhancements on MRI, and a CSF cryptococcal antigen titer of >1:1,024. SNHL accounted for 30.8% (8/26) of cryptococcal meningitis patients in our study.