Primary AA type amyloidosis of the urinary bladder: a case report

Primary amyloidosis of the urinary bladder is a rare disease entity. A total of 61 cases have been reported in the Japanese literature, and most of them were AL type amyloidosis. We report here a case of primary AA type amyloidosis. A 52-year-old man presented with a chief complaint of asymptomatic gross hematuria. Cystoscopy revealed yellowish elevated lesions, transurethral mucosal biopsies were performed, and the histopathological diagnosis indicated a primary AA type amyloidosis of the urinary bladder. Systemic amyloidosis was clinically eliminated. The yellowish lesions in the bladder through cystoscopy disappeared spontaneously one year later without any specific treatment, but periodical work-up may be necessary to rule out recurrence of the disease or bladder tumor.     

Trastuzumab-mediated antibody-dependent cellular cytotoxicity against esophageal squamous cell carcinoma.

PURPOSE: In the present study, we investigated the degree of protein expression and gene amplification of HER-2 in esophageal squamous cell carcinoma (SCC) cell lines and freshly isolated tumors, and trastuzumab-mediated biological activity, in particular antibody-dependent cellular cytotoxicity (ADCC) against HER-2-expressing esophageal SCC cell lines. EXPERIMENTAL DESIGN: Ten different SCC cell lines with various levels of HER-2 status evaluated by flow cytometry, immunocytochemistry (HercepTest), and fluorescence in situ hybridization were evaluated for ADCC, growth inhibitory, or apoptosis-inducing activities mediated by trastuzumab. RESULTS: Trastuzumab induced ADCC against HER-2-expressing esophageal SCC and the activities reflected the degree of HER-2 expression analyzed by flow cytometric analysis, but not by HercepTest nor fluorescence in situ hybridization analysis. Furthermore, trastuzumab-mediated ADCC against transforming growth factor-beta-producing SCC was enhanced by the treatment with SB-431542, which is a selective inhibitor of the phosphorylation induced by transforming growth factor-beta. There were very marginal effects of anti-proliferative or apoptosis-inducing activities mediated by trastuzumab for HER-2-expressing esophageal SCC. CONCLUSION: HER-2-expressing esophageal SCC cells could be killed by trastuzumab-mediated ADCC and the activity reflected the degree of HER-2 expression detected by flow cytometry.     

Potentially Life-threatening Arrhythmia Triggered by an Excessive Consumption of Dried Sweet Potato “Hoshi-Imo”

We herein report two cases of potentially life-threatening arrhythmia due to hyperkalemia triggered by the excessive consumption of “Hoshi-Imo” (dried sweet potato). Both patients with chronic renal disease on renin-angiotensin-aldosterone system inhibitors presented at the emergency room with non-specific symptoms. Electrocardiograms revealed potentially life-threatening arrhythmia due to hyperkalemia in both cases: sinus arrest with a ventricular escape rhythm, tall and peaked T waves; and a widened QRS complex in a nearly sine-wave configuration without discernible P wave. Both patients fully recovered after intensive care for hyperkalemia. Physicians should recognize the excessive consumption of “Hoshi-Imo” may lead to the development of life-threatening arrhythmia, especially in patients with risk factors for hyperkalemia.     

Phthalates rapidly increase production of reactive oxygen species in vivo: role of Kupffer cells

The role of oxidants in the mechanism of tumor promotion by peroxisome proliferators remains controversial. The idea that induction of acyl-coenzyme A oxidase leads to increased production of H(2)O(2), which damages DNA, seems unlikely; still, free radicals might be important in signaling in specialized cell types such as Kupffer cells, which produce mitogens. Because hard evidence for increased oxidant production in vivo after treatment with peroxisome proliferators is lacking, the spin-trapping technique and electron spin resonance spectroscopy were used. Rats were given di(2-ethylhexyl) phthalate (DEHP) acutely. The spin trapping agent alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone was also given and bile samples were collected for 4 h. Under these conditions, the intensity of the six-line radical adduct signal increased to a maximum value of 2.5-fold 2 h after administration of DEHP, before peroxisomal oxidases were induced. Furthermore, DEHP given with [(13)C(2)]dimethyl sulfoxide produced a 12-line electron spin resonance spectrum, providing evidence that DEHP stimulates (*)OH radical formation in vivo. Furthermore, when rats were pretreated with dietary glycine, which inactivates Kupffer cells, DEHP did not increase radical signals. Moreover, similar treatments were performed in knockout mice deficient in NADPH oxidase (p47(phox) subunit). Importantly, DEHP increased oxidant production in wild-type but not in NADPH oxidase-deficient mice. These data provide evidence for the hypothesis that the molecular source of free radicals induced by peroxisome proliferators is NADPH oxidase in Kupffer cells. On the contrary, radical adduct formation was not affected in peroxisome proliferator-activated receptor alpha knockout mice. These observations represent the first direct, in vivo evidence that phthalates increase free radicals in liver before peroxisomal oxidases are induced.     

A 12-year, prospective study of extraocular muscle imaging in complex strabismus

INTRODUCTION: Diagnostic imaging by magnetic resonance imaging (MRI) or computed x-ray tomography (CT) has become the standard of care in many medical fields. Clinical imaging of the extraocular muscles (EOMs) can now provide insight into some causes of strabismus, in some cases challenging traditional concepts of etiology and suggesting alternative treatments. METHODS: Between 1990 and 2001, 62 orthotropic volunteers and 261 strabismic patients underwent orbital imaging under a prospective protocol. Surface coil MRI was performed with fixation control with slice thickness of 1.5 to 3 mm; CT was performed with 1-mm slice thickness. Images were correlated with ophthalmological examinations. RESULTS: MRI was performed in 267 and CT in 56 subjects. Comparison with normal orbits commonly demonstrated abnormalities of EOM size or location in strabismic patients. These included absence (5 patients) or atrophy (33 patients) of the superior oblique (SO) muscle in SO palsy; abnormalities of the trochlea or SO tendon in Brown's syndrome (8 patients); heterotopy of the rectus pulleys associated with incomitant strabismus (46 patients), including instability of pulleys (9 patients); trauma to rectus EOMs (16 patients); atrophy of the lateral rectus (10 patients), inferior rectus (4 patients), medial rectus (4 patients), superior rectus (4 patients), and inferior oblique (1 patient) muscles; and EOMs disinserted by scleral buckles (3 patients). EOM abnormalities correlated closely with clinically abnormal patterns of ocular motility. CONCLUSIONS: With the appropriate technique, EOM imaging is a valuable adjunct in clinical evaluation of complex strabismus. Because imaging can provide unique information unavailable from the clinical examination alone, it should be performed when indicated to evaluate patients with strabismus more complex than concomitant esotropia and exotropia.     

Erk pathways negatively regulate matrix mineralization

Skeletal mineralization is an important step regulating the mechanical properties of the calcified tissues, but molecular events underlying mineralization still remain elusive. We examined the role of extracellular signal-regulated kinase (Erk) pathways in matrix mineralization of osteogenic cells both in vitro and in vivo. Matrix mineralization by preosteocytic MLO-A5 cells and osteoblastic MC3T3-E1 cells was increased by either PD98059 Mek inhibitor treatment or adenovirus vector-mediated dominant negative Ras (Ras(DN)) expression and was suppressed by Erk activation by platelet-derived growth factor (PDGF) treatment or constitutively active Mek1 (Mek(CA)) expression. Administration of adenovirus vectors carrying Ras(DN) gene onto the calvaria of 1-day-old mice increased the mineralization of the tissues, while that of the Mek(CA) adenovirus suppressed it. These results suggest that the Erk pathway is a negative regulator of the matrix mineralization both in vitro and in vivo.     

Asymptomatic chronic intestinal ischemia caused by idiopathic phlebosclerosis of mesenteric vein

Phlebosclerosis of the mesenteric vein is a rare condition causing chronic intestinal ischemia, it has only been reported in Japan. A 56-year-old man with liver cirrhosis and hepatic tumor presented with phlebosclerosis of mesenteric vein without any abdominal symptoms. He was admitted for examination of suspected hepatic tumor. Abdominal plain x-ray films and computed tomography revealed calcification of the mesenteric vein. Barium enema revealed narrowing and thumbprinting from the cecum to transverse colon. On colonoscopic examination, blue-black vessels were visible in the terminal ileum, and hyperemic nodular mucosa with small irregular ulcers surrounded by dark purple mucosa was found from the cecum to transverse colon. The etiology of mesenteric vein phlebosclerosis is unknown, although a physical mechanism rather than inflammatory changes appear to be involved in this rare and usually progressive condition of chronic intestinal ischemia.     

General 2.5 power law of metallic glasses

Metallic glass (MG) is an important new category of materials, but very few rigorous laws are currently known for defining its “disordered” structure. Recently we found that under compression, the volume (V) of an MG changes precisely to the 2.5 power of its principal diffraction peak position (1/q₁). In the present study, we find that this 2.5 power law holds even through the first-order polyamorphic transition of a Ce₆₈Al₁₀Cu₂₀Co₂ MG. This transition is, in effect, the equivalent of a continuous “composition” change of 4f-localized “big Ce” to 4f-itinerant “small Ce,” indicating the 2.5 power law is general for tuning with composition. The exactness and universality imply that the 2.5 power law may be a general rule defining the structure of MGs.Metallic glasses (MGs) possess many unique and superior properties, such as extremely high strength, hardness, and corrosion resistance, etc., making them promising metallic materials with widespread applications (1, 2). Thousands of MGs with a wide range of compositions and properties have been synthesized over the past decades. However, so far the development of MGs is mainly based on tedious composition mapping in multicomponent space to pinpoint the combination of elements with optimized glass-forming ability (GFA). This method for development of MGs is a time- and resource-intensive strategy of trial and error which highlights the need for the guidance of a general theory (2, 3). Intensive research effort has been devoted to finding general rules in various MGs to understand the fundamentals and to guide the development of new MGs (4, 5). Quantitative correlations between their properties have been observed. For instance, compressive yield strength and elastic moduli of MGs are found to be intimately connected with their glass transition temperature T_g (6–10), and the ductility, fragility (11, 12), and Poisson’s ratio of MGs are closely related (13–16). The extensive correlations in properties suggest that the disordered MGs may share general rules in their structure. To clarify this scenario, detailed and accurate structural information spanning short range to long range is required. However, the current experimental probes and theories are limited to local structure in MGs (17). Therefore, understanding how the atoms efficiently fill up the 3D space and how this controls the bulk properties of MGs remains a long-standing theoretical challenge (18–23). To date, few general and exact rules regarding structure–property relationships have been established in MGs (23).Encouraging progress on understanding structure–property relationships in MGs has recently been made through the discoveries of the noncubic (2.3 or 2.5) power laws that correlate the principal diffraction peak (PDP) position q₁ with the bulk density ρ or average atomic volume, V_a, i.e., ρ∝(q₁)^D or V_a∝(1/q₁)^D, where D equals ∼2.3 with varying the composition of MGs at ambient pressure (19) or ∼2.5 for tuning the density of MGs with pressure (22, 24). Whereas composition and pressure show similar exponents in the power laws in MGs, composition and pressure are two independent variables for controlling the density (volume) of materials; they usually have dramatically different effects on MGs. For example, pressure is thought to cause only elastic densification in MGs without obvious structural change because of their already densely packed structure; the structure and properties of MGs are very sensitive to even minor compositional variations (25, 26). In addition, to achieve composition change, different samples usually have to be synthesized. And, many other variables are thought to be inevitably involved, making the compositional change complex (23). Therefore, some basic questions have been perplexing to the glass community: Why do “complex” compositional and “simple” pressure power laws show similar exponents? Is there any connection between them? These questions remain unanswered and have been the major obstacle in understanding the nature of these noncubic power laws.To address these questions, a systematic study in the 2D pressure-composition space seems to be required. However, the consistency of the data in this kind of study will be questionable. Alternatively, in the present study, we choose the polyamorphous Ce₆₈Al₁₀Cu₂₀Co₂ MG as a model system. It is well known that Ce-based MG systems show a polyamorphic transition between ∼2 GPa and ∼5 GPa caused by the pressure-induced 4f electron localized-to-itinerant transition (27, 28). During this polyamorphic transition, both the atomic size and the electronegativity of Ce are significantly changed (29). Composition tuning in MGs mainly means the variation of atomic size and electronegativity of components, which controls the formation of MGs (30). Therefore, although nothing changes in the nucleus, for MGs this pressure-induced polyamorphic transition is equivalent to a continuous “composition” change with the 4f-localized “big Ce” gradually substituted by 4f-itinerant “small Ce.” As a result, we are able to vary both pressure and composition of a MG in a well-controlled way for the first time, to our knowledge.