Tumors of the central nervous system studied by computed tomography and ultrasound

Intraoperative ultrasound (US) was compared to computed tomography (CT) in 41 intracranial and 6 spinal cord tumors. The studies correlated closely except for primary gliomas. Eight of the 22 primary intracranial gliomas (37%), including 1 low-grade and 7 anaplastic tumors, were larger and more extensive on US than on CT. Margins of non-enhanced primary astrocytomas were shown by US but not CT. Four anaplastic tumors (19%) exhibited echogenicity extending beyond the enhanced area. In 4 patients an enhanced lesion contained a lucent center which proved to be echogenic. Low-grade astrocytomas were relatively homogeneous on US, while anaplastic astrocytomas were more inhomogeneous. Cysts could be found in both types of astrocytomas and were often small and multiple. The echo pattern was not helpful in differentiating metastases from primary tumors, although all of them had sharp margins. Sonography of the central nervous system can provide valuable information about tumor morphology and margins.     

Homozygous deletion mutations in the plectin gene (PLEC1) in patients with epidermolysis bullosa simplex associated with late-onset muscular dystrophy

In a distinct autosomal recessive variant of epidermolysis bullosa, EB- MD, life-long skin blistering is associated with late-onset muscular dystrophy of unknown etiology. Electron microscopy of these patients' skin suggests that tissue separation occurs intracellularly at the level of the hemidesmosomal inner plaque, which contains plectin, a high molecular weight cytoskeletal associated protein, also expressed in the sarcolemma of the muscle. In this study, we report two patients with EB-MD, each with a homozygous deletion mutation in the plectin gene, PLEC1. In the first case, the proband and her similarly affected sister had a homozygous 9 bp deletion mutation, designated as 2719de19, which resulted in elimination of three amino acids, QEA, in a sequence of 23 amino acids entirely conserved between the mouse and human sequences. The proband in the second family demonstrated a single nucleotide deletion at position 5866, designated as 5866delC, which resulted in frameshift and a premature termination codon for translation 16 bp downstream from the site of deletion. The absence of plectin in the hemidesmosomes, as reflected by negative immunofluorescence with an anti-plectin antibody (HD-1), associated with fragility of basal keratinocytes, implicates plectin as critical for binding of intermediate keratin filament network to hemidesmosomal complexes. The function of plectin as a putative attachment protein also in the muscle would explain the clinical phenotype consisting of cutaneous fragility and muscular dystrophy in EB-MD.      

Molecular evidence that in situ-transduced fetal liver hematopoietic stem/progenitor cells give rise to medullary hematopoiesis in adult rats

We exploited the ability to transduce fetal liver hematopoietic stem/progenitor cells in situ with recombinant retrovirus, together with the ability to analyze proviral integration patterns into chromosomal DNA, to detect the cellular and organ fate of hematopoietic stem and progenitor-derived progeny in tissues and in the circulation of neonatal and adult rats. Two hundred seventeen fetuses were injected with retrovirus supernatant on day 16 of gestation, before the development of the bone marrow cavity. The progeny of 41 stem and progenitor cells from 97 liveborn rats were clonally identified. Pluripotent and lineage-restricted stem/progenitor clones derived from the fetal liver consistently gave rise to progeny in the marrow of newborn and adult rats. Patterns of differentiation of transduced stem and progenitor cells fell into distinct subsets. Blood cells derived from in situ transduced cells that originated in the fetal liver circulated throughout the life span of the adult animals. These data provide molecular evidence of the origin of medullary cavity hematopoiesis by cells derived from the fetal liver that were transduced in vivo, homed to the developing medullary cavity and proliferated in a normal medullary hematopoietic microenvironment.     

A human monoclonal antibody specific for the leucine-33 (P1A1, HPA-1a) form of platelet glycoprotein IIIa from a V gene phage display library

IgG alloantibodies to polymorphic platelet glycoproteins (GPs) are known to be responsible for severe thrombocytopenia in the neonate and after transfusion. Platelet GPIIIa can have either a leucine or a proline at residue 33. The most immunogenic platelet alloantigen in thrombocytopenia is the leucine 33 form of GPIIIa. Here, we have generated human monoclonal antibody fragments that are specific for the leucine and not the proline form of GPIIIa and can inhibit the binding of polyclonal human IgG alloantibodies to GPIIIa leucine 33 on platelets. The antibody fragments were selected from a library of single chain Fv fragments displayed on the surface of filamentous phage. The VH gene repertoire was derived from the peripheral blood lymphocytes of an alloimmunized individual and recombined with a VL gene repertoire from a nonimmune source. Antibodies such as these, which are able to distinguish between two variant forms of a native antigen and which have been unobtainable by conventional hybridoma technology, have both diagnostic and potential therapeutic applications.     

肌松药物巴氯芬类似物的合成及其构效关系的研究

为研究解痉肌松药巴氯芬类似物的构效关系,合成了巴氯芬类似物15个,其中8个化合物是首次报道。采用小白鼠热板法及对抗吗啡竖尾反应实验评价目标化合物的镇痛和肌松作用。筛选结果表明:部分化合物有肌松和镇痛作用,其中Ⅰb,Ⅱb,Ⅲa和Ⅲc的镇痛作用较好,Ⅰd,Ⅱb,Ⅲa和Ⅲb的肌松作用较好,但均未超过巴氯芬。根据本研究及前人的研究结果,提出巴氯芬与GABA_B受体结合取决于巴氯芬分子中氨基、羧基和苯环三种基团。     

Computed tomography in untreated adults with virilizing congenital adrenal cortical hyperplasia

Thirteen adult patients with biochemically proven congenital adrenal hyperplasia (CAH) were examined by computed tomography (CT). Six patients had never received glucocorticoid therapy. In three of those six patients, CT revealed a tumorous transformation in one of the hyperplastic adrenal glands. In the seven patients with CAH who were treated since childhood, no mass could be demonstrated on CT. The development of an adrenocortical tumour due to chronic adrenal cortical stimulation by excessive adreno-cortico-trophic hormone (ACTH) production in adult patients with untreated CAH may not be a rare occurrence, as is demonstrated in this series. It is important not to confuse this entity with a primary virilizing adrenal tumour which requires a different form of treatment. In case of tumorous transformation in untreated adults with CAH, suppressive therapy with CT control should be favoured over surgery, as long as the tumour is ACTH-dependent. Moreover, these observations illustrate the desirability of lifelong glucocorticoid therapy in patients with CAH, including adult males who biochemically may not require suppression of steroid androgen excess.     

Bizarre parosteal osteochondromatous proliferation of the hands and feet

Two adults with bizarre parosteal osteochondromatous proliferation of the hands and feet are presented. The pre-operative diagnosis may be difficult to make and the correct diagnosis was not made in either case until pathological examination of recurrent tumour masses occurred. The radiological and pathological features of this lesion are discussed. The diagnostic features which differentiate this condition from other causes of new bone formation in the peripheries are described.     

Clinical and experimental vasogenic edema: in vivo sodium MR imaging. Work in progress

To investigate the sodium magnetic resonance (MR) imaging characteristics of acute vasogenic edema, an experimental canine model was developed. Vasogenic edema was produced in the hemisphere of the dogs by the intraarterial infusion of hypertonic mannitol (25%). This solution opens the blood-brain barrier, allowing the influx of water, electrolytes, and proteins into the brain. The main advantage of this model over the established "cold injury" model is the lack of associated brain necrosis. Two patients with chronic vasogenic edema secondary to well-circumscribed meningiomas also underwent MR imaging. The sodium signal was markedly elevated in both clinical and experimental studies of vasogenic edema fluid compared with signal in healthy brain tissue. Extracellular sodium associated with vasogenic edema displayed MR imaging characteristics similar to that of sodium in serum. There was a trend toward a shortened T2 in edema fluid secondary to the presence of serum macromolecules.     

Colonic wall thickness, pancreatic enzyme dose and type of preparation in cystic fibrosis

Increased colonic wall thickness has been reported in patients exposed to large doses of high strength pancreatic enzyme preparations who did not develop fibrosing colonopathy. This has been interpreted as evidence for a spectrum of subclinical disease. The relation between sonographically measured colonic wall thickness and pancreatic enzyme preparation and dose was studied in 86 children with cystic fibrosis (CF). Colonic wall thickness of a control group was also measured. The average thickness in all colonic regions was higher in the CF group (overall average range 0.7-2.5 mm v 0.6-1.4 mm in the control group). There was no significant relation between colonic wall thickness and age, sex, total dose of lipase, or copolymer. Apart from one patient with an early colonic stricture, none of those exposed to high doses of lipase, or the methacrylic acid copolymer Eudragit L30 D55, showed evidence of subclinical damage to the colon. The reproducibility of the sonographic measurements was poor.