Oral Langerhans cell histiocytosis in Malaysian children: a 40-year experience

Background.  Oral Langerhans cell histiocytosis is generally seen in children.
Objective.  To determine the clinicopathological features of oral LCH in Malaysian paediatric patients.
Methods.  A retrospective study was carried out to determine the clinicopathological features of Langerhans cell histiocytosis (LCH), Letterer–Siwe disease, Hand–Schuller–Christian disease, eosinophilic granuloma, and histiocytosis X occurring in the oral cavity in children, diagnosed histologically in the main oral histopathology laboratory in Malaysia from 1967 to 2007.
Result.  There were 17 cases (eight girls and nine boys) with age ranging from 1 to 7 years. There were ten Malays, four Chinese, two Indians, and one of other ethnicity. Thirteen cases presented as gingival swellings with six of these cases accompanied with mobility of the teeth. Nine cases involved the mandible, two in the maxilla, and two cases in both the maxilla and mandible. The radiographic findings were mentioned only in nine cases with presence of bony erosion or destruction of the jaw bones. Four cases had punched-out radiolucencies of the skull. The patients also had other systemic signs and symptoms: skin lesions ( n  = 5), hepatosplenomegaly ( n  = 2), prolonged fever ( n  = 2), diabetes insipidus ( n  = 1), and exophthalmos ( n  = 1). Two cases were known cases of systemic LCH.
Conclusion.  The histopathologic features of LCH are easily recognized; however, with the development of immunostaining, the use of CD1a helps in confirming the diagnosis.     

hCG和LHRH-A对人早孕和孕终末期胎盘绒毛分泌孕酮作用的体外研究

在妊娠的不同时期,胎盘中黄体生成素释放激素(LHRH)的含量不同。离体培养的绒毛组织实验也发现,相同剂量的外源性LHRH对妊娠中期和终末期胎盘绒毛组织分泌hCG和孕酮作用强度也不同。本实验室曾发现,LHRH类似物(LHRH-A)对体外培养孕早期(10～12周)和孕终末期(38～40周)绒毛组织分泌hCG均有兴奋作用,但对分泌孕酮的作用不同,即LHRH-A对早孕绒毛分泌孕酮有抑制作用,而对终末期分泌孕酮     

Bilateral activation of fronto-parietal networks by incrementing demand in a working memory task

Working memory (WM) is known to activate the prefrontal cortex. In the present study we hypothesized that when additional contingencies are added to the instruction of a WM task, this would increase the WM load and result in the activation of additional prefrontal areas. With positron emission tomography we measured regional cerebral blood flow in nine subjects performing a control task and two delayed matching to sample tasks, in which the subjects were matching colours and patterns to a reference picture. The second of the two delayed matching tasks had a more complex instruction than the first, with additional contingencies of how to alternate between the matching of colours and patterns. This task thus required the subjects not only to remember a stimulus to match but also to perform this matching according to a specified plan. Both delayed matching tasks activated cortical fields in the middle frontal gyrus, the frontal operculum, upper cingulate gyrus, inferior parietal cortex and cortex lining the intraparietal sulcus, all in the left hemisphere. When alternated delayed matching was compared to simple delayed matching, increases were located in the right superior and middle frontal gyrus and the right anterior inferior parietal cortex. The increased demand during alternated matching thus resulted in bilateral activation of both dorsolateral prefrontal and inferior parietal cortex. The area in the inferior parietal cortex has previously been coactivated with the dorsolateral prefrontal cortex in several WM tasks, irrespective of the sensory modality of the stimuli, and during tasks involving planning.      

Endosomal proteolysis regulates calcitonin gene-related peptide responses in mesenteric arteries

Background and Purpose

Calcitonin gene-related peptide (CGRP) is a potent vasodilator, implicated in the pathogenesis of migraine. CGRP activates a receptor complex comprising, calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein 1 (RAMP1). In vitro studies indicate recycling of CLR•RAMP1 is regulated by degradation of CGRP in early endosomes by endothelin-converting enzyme-1 (ECE-1). However, it is not known if ECE-1 regulates the resensitization of CGRP-induced responses in functional arterial tissue.

Experimental Approach

CLR, ECE-1a-d and RAMP1 expression in rat mesenteric artery smooth muscle cells (RMA-SMCs) and mesenteric arteries was analysed by RT-PCR and by immunofluorescence and confocal microscopy. CGRP-induced signalling in cells was examined by measuring cAMP production and ERK activation. CGRP-induced relaxation of arteries was measured by isometric wire myography. ECE-1 was inhibited using the specific inhibitor, SM-19712.

Key Results

RMA-SMCs and arteries contained mRNA for CLR, ECE-1a-d and RAMP1. ECE-1 was present in early endosomes of RMA-SMCs and in the smooth muscle layer of arteries. CGRP induced endothelium-independent relaxation of arteries. ECE-1 inhibition had no effect on initial CGRP-induced responses but reduced cAMP generation in RMA-SMCs and vasodilation in mesenteric arteries responses to subsequent CGRP challenges.

Conclusions And Implications

ECE-1 regulated the resensitization of responses to CGRP in RMA-SMCs and mesenteric arteries. CGRP-induced relaxation did not involve endothelium-derived pathways. This is the first report of ECE-1 regulating CGRP responses in SMCs and arteries. ECE-1 inhibitors may attenuate an important vasodilatory pathway, implicated in primary headaches and may represent a new therapeutic approach for the treatment of migraine.     

LHRH类似物的设计和合成

为了寻找新的高效LHRH类似物,设计并合成了带有(D-Trp~6、desGly~(10))-LHRHEA,(D-Arg~6,desGly~(10))-LHRHEA变换5位残基的六个类似物。并应用体外黄体细胞培养法测定了它们的生理活性。     

Superior vena cava syndrome associated with massive thrombosis: treatment with expandable wire stents

Two patients with superior vena cava syndrome (SVCS) associated with massive thrombosis were treated by means of local thrombolytic therapy and placement of modified Gianturco expandable wire stents. Treatment resulted in complete resolution of the SVCS symptoms. The combination of local thrombolytic therapy and stent placement allows a more aggressive approach to treatment of SVCS and provides longer-term palliation of symptoms even for patients with later stages of the disease.     

Measurement of benzene oxide in the blood of rats following administration of benzene

Although it is generally assumed that metabolism of benzene proceeds through an initial step involving oxidation to benzene oxide (BO) by CYP450 in the liver, the production of BO has never been unambiguously confirmed in animals dosed with benzene. Furthermore, prevailing hypotheses of the mechanism by which benzene causes cancer have ignored the possibility that BO might play a direct role, despite the fact that BO is electrophilic, binds covalently to cell macromolecules and is presumably genotoxic. A likely reason for this lack of attention to the role of BO in the carcinogenesis of benzene is the presumption that this epoxide is too reactive to escape the hepatocyte after it is formed. We employed gas chromatography-mass spectrometry to measure BO in the blood of F344 rats, both in vitro and up to 24 h following oral administration of benzene. Surprisingly, BO was relatively stable in rat blood at 37 degrees C (estimated half-life = 7.9 min) and, after administering a single dosage of 400 mg benzene/kg body wt, a blood concentration of 90 nM BO (8.5 ng/ml) was measured for approximately 9 h. Using a published PBPK model we estimate that approximately 4.3% of the metabolized dose of benzene was released as BO from the liver into blood. This confirms that BO is, indeed, formed from metabolism of benzene and is sufficiently stable to be distributed throughout the body at levels which are likely to be greater than those of the other electrophilic benzene metabolites.