Bioaccumulation of lead in wildlife dependent on the contaminated environment of the Kafue flats.
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Biomedical subjects
Publications and source records attributed to Y Nakazato.
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Refractile eosinophilic granular cells (rEGCs), which are distinct from the previously reported eosinophilic granular cells in oligodendroglial tumors, were characterized. The granules of rEGCs showed intense eosinophilia and prominent refractility, and were arranged in clusters or piled up in the perikaryon. The rEGCs tended to distribute in the vicinity of fibrovascular stroma and collagenous areas. They appeared in oligodendroglial tumors with numerous minigemistocytes and gliofibrillary oligodendrocytes. More rEGCs were present in WHO grade III oligodendroglial tumors. Histochemically, the granules stained blue with Kluver-Barrera and vividly red with Masson's trichrome stain, but negative with periodic acid-Schiff reagent. Almost all of the rEGCs were immunopositive for glial fibrillary acidic protein (GFAP) and heat shock protein 27 (HSP27), and some of them showed immunopositivity with alphaB-crystallin. No MIB-1 immunopositivity of rEGCs was found. Ultrastructurally, the rEGCs had many ellipsoidal structures associated with bundles of glial fibers in the cytoplasm. The morphological features of granules of rEGCs were similar to those of Rosenthal fibers except for the size and shape of the structure. We considered that the rEGCs originated from overexpression and accumulation of alphaB-crystallin and HSP27 in GFAP-positive oligodendroglial cells due to various pathological conditions. The presence of the rEGCs in the oligodendrogliomas may suggest more aggressive clinical behavior of tumors.
BACKGROUND: Pineal apoplexy is a rare apoplectic event in the pineal region with various possible causes. We report a case of massive hemorrhage in the pineal region associated with a cavernous angioma, and discuss the pathogenesis of pineal apoplexy. CASE DESCRIPTION: An 11-year-old girl presented with nausea and vomiting persisting for 1 week. Neuroimaging revealed enlarged ventricles and a 4 cm round mass in the pineal region consistent with hematoma. Two weeks after cerebrospinal fluid drainage, the mass was totally removed via the occipital transtentorial approach. The postoperative course of the patient was uneventful. Magnetic resonance imaging after the operation confirmed two paraventricular lesions with surrounding hemosiderin rings, characteristic of cavernous angioma. Histologic examination showed large hematomas and numerous vascular spaces lined by a single layer of endothelium. The diagnosis was pineal apoplexy associated with cavernous angioma, based on the histologic and radiological findings. CONCLUSIONS: Pineal cavernous angiomas are extremely rare, with only fourteen cases reported previously. We recommend total removal of the causative lesion in cases of pineal apoplexy to prevent repeated bleeding or life-threatening massive hemorrhage.
BACKGROUND: Hemangioblastoma (HBL) in the suprasellar region is extremely rare. CASE DESCRIPTION: A suprasellar mass was found in a 33-year-old woman with retinal HBL and bilateral adrenal pheochromocytomas. The diagnosis of von Hippel-Lindau (VHL) disease was confirmed preoperatively not only by these clinical manifestations but also by germline mutation study. The existence of VHL disease indicated a diagnosis of HBL for the suprasellar mass. The results of our mutation study indicated that this patient had type II VHL disease, suggesting that careful follow-up is essential for the early detection of renal cell carcinoma, which is often associated with type II VHL disease. Here, we summarize the previously reported features of sellar and suprasellar HBLs. CONCLUSIONS: HBLs in this region may be one manifestation of VHL disease. Genetic testing of the VHL gene of our patient could provide useful information to determine appropriate medical care and management.
Various histological types of tumors arise in the pineal region. The most common tumors are pineal parenchymal tumors and germ cell tumors. Pineal parenchymal tumors are divided into pineocytoma, pineal parenchymal tumor with intermediate differentiation and pineoblastoma. Pineocytomas are well-differentiated tumors and retain the morphological and immunohistochemical features of pineal parenchymal cells. Lobular architectures and pineocytomatous rosettes are also typical features. In contrast, pineoblastomas are embryonal tumors resembling primitive neuroectodermal tumors (PNET). However, pineoblastomas are distinct from PNET in other sites due to their exhibiting photosensory differentiation including Flexner-Wintersteiner rosettes and fleurettes. Although pineal cysts are tumor-like lesions, and not true neoplasms, they are occasionally difficult to distinguish from pineocytoma and astrocytoma. From the therapeutic aspect, a precise differential diagnosis is critical. The pineal region is the most common site of the brain in which germ cell tumors occur. Germinoma, teratoma, embryonal carcinoma, yolk sac tumor and choriocarcinoma are encountered, and the latter three types of tumors usually constitute elements of mixed germ cell tumors. The morphological and immunohistochemical features of intracranial germ cell tumors are very similar to those of gonadal germ cell tumors, although there are some differences in germinoma. Pineal germinoma may exhibit carcinomatous differentiation. Other types of tumors are occasionally observed, including fibrillary and pilocytic astrocytoma, glioblastoma, ependymoma, melanoma, meningioma and so on. Metastatic pineal tumors are also rare. The most common site of origin for pineal metastasis is the lung.
The effects of nicotinic agonists and antagonists on whole-cell currents and 5-hydroxytryptamine (5-HT) release were studied in order to characterize nicotinic ACh receptors on the 5-HT-containing chemoreceptor cells of the chicken aorta. ACh, nicotine and dimethylphenylpiperazinium (DMPP) evoked concentration-dependent inward currents accompanied by increases in current noise at a holding potential of -70 mV. The peak amplitude of the current response to DMPP was 50% larger than that to either nicotine or ACH: Hexamethonium, alpha - bungarotoxin (alpha - BTX) and methyllycaconitine decreased nicotine-induced inward currents in a concentration-dependent manner. Although hexamethonium (0.1 mM) abolished the current response to nicotine (30 microM), a high concentration (1 microM) of alpha - BTX decreased it only by about 30% of the control response. Methyllycaconitine (0.1 microM) decreased the current response to nicotine to the same extent as did alpha - BTX whilst a high concentration (10 microM) abolished the response. ACh, nicotine and DMPP caused concentration-dependent increases in 5-HT output from the thoracic aorta which effect was blocked by hexamethonium (0.1 mM). Pre-treatment with alpha - BTX (1 microM) for 30 min reduced the output of 5-HT induced by ACh to 70% of the control response. It is suggested that neuronal nicotinic ACh receptors, sensitive and insensitive to alpha - BTX, are present on the chemoreceptor cells of the chicken aorta, the activation of which causes the release of 5-HT.
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A potential novel variant of meningioma is reported. The tumor was solid, hard, white-colored, well circumscribed in a fibrous capsule and fixed to the dura, showing no invasion into the brain parenchyma. Histopathological study presented a sparsely cellular tumor composed of cells with fine reticular or mesh-like cytoplasm, each containing an oval nucleus. Mitotic figures were rarely seen. Immunohistochemical studies of tumor cells showed positive immunoreactivity for vimentin and epithelial membrane antigen but were negative for GFAP, desmin, neurofilament, keratin, S-100, CD34 and CEA. Bipolar neoplastic cells and long processes were noted on ultrastructural observation; these were attached side by side to each other by desmosomes, resulting in a mesh-like configuration. Perinuclear cytoplasm and processes were rich in intermediate filaments and rough endoplasmic reticulum. These microscopic and ultrastructural features have never before been reported among the variants of meningioma. The name 'meshy meningioma' is proposed for this novel variant.
A 25-year-old man was admitted to the Department of Neurology, Gunma University Hospital, in June 1997. He had an intellectual disability and had suffered from repeated infection since childhood. Cerebellar ataxia had developed at 19 years of age and he had been clinically diagnosed with ataxia telangiectasia (AT) comprising cerebellar ataxia and oculocutaneous telangiectasia at 24 years of age. He died from pneumonia and renal failure at 26 years of age. Neuropathological examination revealed Purkinje cell loss and atrophy of the dentate nuclei in the cerebellum, anterior horn-cell atrophy and demyelination of the gracile fasciculi in the spinal cord, and the existence of nucleocytomegalic cells in the anterior pituitary gland. These neuropathological findings correlated with previously reported cases of AT. In addition, spongy degeneration was found, predominantly around the blood vessels in the cerebral cortex. Diffuse spongy degeneration and multiple foci of coagulative necrosis with calcification were noted in the white matter. Abnormal vasculature was noted in both degenerative and necrotic areas in the cerebral cortex and in the white matter. The vessels at the center of the areas of spongy degeneration in the cerebral cortex had irregularly arranged and enlarged smooth-muscle-cell nuclei and a distorted, narrow lumen. The vessels present in the white matter were hyalinized. To our knowledge, these vascular abnormalities in the brain parenchyma have not been reported previously.
Patients with neurofibromatosis type 1 (NF1) often have gliomas as a complication, most of which are benign pilocytic astrocytomas which have arisen in optic pathways. In the present case, a 17-year-old girl (at death) with stigmata of NF1, initially had a bulky tumor mass in the left thalamus, developing into the lateral ventricle, at 13 years of age. Partially resected tissue samples showed pleomorphic astrocytoma with abundant xanthoma cells and degenerative structures such as Rosenthal fibers (RF) and eosinophilic granular bodies. Fine eosinophilic granules identical to RF, both immunophenotypically and ultrastructurally, were also seen. The residual tumor was subtotally resected 6 months later, and the tumor histology was essentially similar as before, accompanying the regenerative structures; this was believed to be a good prognostic indicator. However, several anaplastic features such as mitosis, necrosis and vascular proliferation appeared even in areas rich in the regenerative structures. After a 2-year, disease-free interval, multiple tumor relapse occurred in June 1997. Partially resected tumor tissues were composed of monotonous small anaplastic cells with prominent proliferative activity. Surprisingly, the tumor cells had retained eosinophilic granules within the cell bodies. Postoperative chemotherapy with procarbazine, MCNU and vincristine (PCV) suppressed the residual tumor dramatically, but the regrowing tumor finally became uncontrollable, leading to the patient's death. TP53 mutation was not detected, while p27 immunopositivity was constantly high during malignant progression, suggesting acquisition of proliferative activity to overcome p53 and p27 inhibitory functions. A review of previously published reports failed to reveal any cases of this type.
We characterized changes in membrane currents and the cytosolic Ca(2+) concentration, [Ca(2+)](i), in response to caffeine, and compared them with those in response to muscarine using the perforated patch-clamp technique and fura-2 microfluorimetry in guinea-pig adrenal chromaffin cells. Catecholamine release from single voltage-clamped cells was monitored with amperometry using carbon microelectrodes. Caffeine produced a transient outward current (I(out)) at holding potentials over - 60 mV, increasing in amplitude with increasing the potentials. It also evoked a rapid increase of [Ca(2+)](i) at all potentials examined. The current-voltage relation revealed that the activation of K(+) channels was responsible for the I(out) evoked by caffeine. Both current and [Ca(2+)](i) responses were reversibly abolished by cyclopiazonic acid, an inhibitor of Ca(2+)-pump ATPase. At - 30 mV, the caffeine-induced I(out), but not [Ca(2+)](i), was partly inhibited by either charybdotoxin or apamin. In the majority of cells tested, caffeine induced a larger I(out) but a smaller [Ca(2+)](i) increase than muscarine. Caffeine and muscarine increased catecholamine release from voltage-clamped single cells concomitant with the transient increase of [Ca(2+)](i), and there was a positive correlation between them. These results indicate that caffeine activates Ca(2+)-dependent K(+) channels and catecholamine secretion due to the release of Ca(2+) from internal stores in voltage-clamped adrenal chromaffin cells of the guinea-pig. There seems to be a spatial difference between [Ca(2+)](i) increased by Ca(2+) release from caffeine-sensitive stores and that released from muscarine (inositol 1,4,5-trisphosphate)-sensitive ones.
Transgenic mice overexpressing hepatocyte growth factor/scatter factor (HGF/SF) demonstrate extensive pigmented nevi in both skin and leptomeninges of the central nervous system resembling human neurocutaneous melanosis. We immunohistochemically detected HGF/SF receptor, Met, in a congenital nevus of an infant with neurocutaneous melanosis, indicating that deregulation of HGF/SF-Met signaling in the critical period of development may lead to this fatal syndrome.
We report on a 62-year-old woman without Castleman's syndrome diagnosed with chordoid meningioma. A white, encapsulated brain tumor was located in the parietal lobe of the left hemisphere of the cerebrum, adhered to the dura, and was separated from the cerebrum. The tumor revealed a multilobular arrangement of two types of neoplastic cells, and the surrounding myxoid stroma was separated by incomplete fibrous septa. Neoplastic cells consisted of myxomatous and meningothelial cells. The former made up about four-fifths of the tumor, had a vacuolar cytoplasm, and were arranged in a chordoma-like cord pattern. They were floating in myxoid stroma. The latter had an eosinophilic spindle or epithelioid cytoplasm and were disposed in lobules. Coarse eosinophilic materials positive for periodic acid-Schiff stain were deposited among them. Transitional cells between two types of cells were also observed. Both neoplastic cells were positive for vimentin and Leu-7 (CD57) in their cytoplasm, and were consistently negative for epithelial membrane antigen, S-100 protein, and cytokeratin.
Recent studies have suggested that both the angiotensin II type 1 (AT1) and type 2 (AT2) receptors may be involved in the control of renal function in rodents. The aim of this study was to examine the distribution of these receptors in normal and diseased human kidneys. Kidney samples were obtained from 21 patients with and without glomerular lesions (3 control kidney samples from patients undergoing nephrectomy, 4 patients with minimal change disease, 6 patients with IgA nephropathy, and 8 patients with membranous glomerulonephritis). AT1 receptor immunohistochemical staining was examined and found to be most prominent in blood vessels, but staining of the tubules and glomeruli was also seen. In the case of the AT2 receptor, mild-moderate immunohistochemical staining was seen in the blood vessels, with weaker staining in the glomeruli. A similar distribution was seen in the patients with glomerulopathy. These results suggest that both AT1 and AT2 receptors are expressed in the normal human kidney, as well as in patients with glomerular disease. The histological distribution of these receptors supports the notion that both receptors may have a physiological role in normal and diseased kidneys in humans.
Electrocardiographic changes were evaluated retrospectively in five patients without previous episodes of syncope or ventricular fibrillation who developed abnormal ST segment elevation mimicking the Brugada syndrome in leads V1-V3 after the administration of class Ic antiarrhythmic drugs. Pilsicainide (four patients) or flecainide (one patient) were administered orally for the treatment of symptomatic paroxysmal atrial fibrillation or premature atrial contractions. The QRS duration, QTc, and JT intervals on 12 lead surface ECG before administration of these drugs were all within normal range. After administration of the drugs, coved-type ST segment elevation in the right precordial leads was observed with mild QRS prolongation, but there were no apparent changes in JT intervals. No serious arrhythmias were observed during the follow up periods. Since ST segment elevation with mild QRS prolongation was observed with both pilsicainide and flecainide, strong sodium channel blocking effects in the depolarisation may have been the main factors responsible for the ECG changes. As the relation between ST segment elevation and the incidence of serious arrhythmias has not yet been sufficiently clarified, electrocardiographic changes should be closely monitored whenever class Ic drugs are given.
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Excess fibroblasts and inflammatory cells may play an important role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). The small GTPase, Rho, and its target protein, Rho-associated coiled-coil-forming protein kinase (ROCK), have been recognized to be major regulators of cell locomotion mediated by reorganization of the actin cytoskelton. Activated ROCK inhibits myosin phosphatase, and this in turn induces phosphorylation of the myosin light chain (MLC). To determine the mechanisms underlying the deterioration process of IPF, we investigated the effect of Y-27632, a selective ROCK inhibitor, in a murine model of bleomycin (BLM)-induced lung fibrosis. The Aschcroft score and hydroxyproline content of the BLM-treated mouse lung decreased in response to Y-27632 treatment. The number of broncoalveolar cells was decreased by Y-27632, and migration of macrophages, neutrophils, and fibroblasts in vitro was inhibited by Y-27632 regardless of various stimuli. Although expression of ROCK-II mRNA in the lung homogenates of the BLM-treated mice was increased approximately 9-fold, expression of ROCK-II protein showed only a slight tendency to increase. BLM elevated MLC phosphorylation levels, and Y-27632 inhibited BLM response. These findings indicate that the Rho/ROCK-mediated pathway plays an important role in IPF, and that blocking of this pathway leads to inhibition of IPF development.
Exposure and ecological risks to heavy metals (copper, zinc, manganese, iron) at Lochnivar and Blue Lagoon National Parks in wildlife dependent on the Kafue river contaminated with mining waste was evaluated. Samples included water, fish, grasses and Kafue Lechwe (Kobus leche kafuensis) liver. At both parks copper ranged from 0.03-0.04 mg/l; 3.0-6.0 mg/kg; 11.0-44.0 mg/kg; trace -199.0 mg/kg; while zinc was 0.01 mg/l; 32.0-82.0 mg/kg; 15.0-21.0 mg/kg; and 52.0-138.0 mg/kg; in water, fish, grasses and lechwe, respectively. Manganese ranges were 0.15-0.16 mg/l; 7.0-18.0 mg/kg; 51.0-145.0 mg/kg; and 40.0-53.0 mg/kg while iron ranges were 0.13-0.14 mg/l; 26.0-134.0 mg/kg; 1766.0-1797.0 mg/kg; and 131.0-856.0 mg/kg; in water, fish, grasses and lechwe, respectively. Levels in all samples except water were high indicating potential for adverse effects.