Cloning and expression of the gene involved in Sanfilippo B syndrome (mucopolysaccharidosis III B)

Sanfilippo B syndrome is caused by a deficiency of alpha-N- acetylglucosaminidase, a lysosomal enzyme involved in the degradation of heparan sulphate. Accumulation of the substrate in lysosomes results in degeneration of the central nervous system with progressive dementia often combined with hyperactivity and aggressive behaviour. In order to clone the deficient gene, we purified the enzyme from human placenta and obtained amino acid sequence information. Alignment of one of the CNBr generated internal peptides to sequence from the database revealed the chromosomal location of the gene in the 5' upstream flanking region of the gene for 17-beta-hydroxysteroid-dehydrogenase at 17q21.1. The available DNA sequence was used to clone the cDNA coding for alpha-N- acetylglucosaminidase and analyse its gene structure. The gene is fully contained in the 5' upstream flanking region of the gene for 17-beta- hydroxysteroid-dehydrogenase and interrupted by five introns. The cDNA clone has a length of 2575 bp and encodes a protein of 743 amino acids. Chinese hamster ovary cells transfected with the cDNA construct show alpha-N-acetylglucosaminidase activity about 17-fold over background. This will allow correction studies with NAG deficient Sanfilippo B cell lines and facilitate the development of enzyme replacement therapy for these patients.      

Circumscribed low grade astrocytomas in the dominant opercular and insular region: A pilot study

Summary Intraoperative mapping techniques allow a reliable identification or exclusion of eloquent brain areas and are well tolerated by the patients. In dominant opercular tumours radical surgery can only be achieved without lasting deficits with intraoperative histological examination of the resection line and mapping. If an early post-operative MRI shows residual opercular tumour in non-eloquent areas re-operation is recommended.In large dominant insular or opercular-insular tumours only biopsy is recommended, because only an incomplete removal can be accomplished, because the trial of radical removal carries a high risk of postoperative deficits due to possible vascular damage of the lenticulo-striate arteries or internal capsule. Because subtotal removal of low grade gliomas does not increase the progression free interval, we would not recommend surgery in these cases, as they carry a significant risk of a further deficit.     

Actions of parathyroid hormone-related protein on the rat kidney in vivo

Peptides containing residues 1-34 of parathyroid hormone-related protein (PTHrP) and of bovine parathyroid hormone (bPTH), and recombinant full-length PTHrP(1-141) were infused i.v. into anaesthetized thyroparathyroidectomized rats to compare their action and potency on the renal handling of calcium, phosphate and cyclic AMP (cAMP) in vivo. All three peptides decreased the excretion of calcium and increased the excretion of phosphate and cAMP in the urine, with PTHrP(1-34) and PTHrP(1-141) having virtually equipotent effects. Thus the essential requirements for the major physiological activity of PTHrP on the kidney are contained within the 34 amino-terminal amino acids. For all three peptides, the lowest infusion rate that increased phosphate and cAMP excretion was 0.01 nmol/kg per h, whereas the lowest infusion rate that decreased calcium excretion was 0.025 nmol/kg per h for the PTHrP peptides and 0.1 nmol/kg per h for bPTH(1-34). The response to the PTHrP peptides was maximal at an infusion rate of 0.1 nmol/kg per h for both calcium and phosphate. Since the kidney is either equally sensitive to PTHrP and bPTH(1-34), or more sensitive to PTHrP than to bPTH(1-34), the hypercalcaemia of humoral hypercalcaemia of malignancy may develop because uncontrolled secretion of PTHrP increases the renal reabsorption of calcium to such an extent that even a modest increase in the inflow of calcium into the blood raises plasma calcium concentration.     

Post-transfusion hepatitis.

Prospective international studies have shown the incidence of post-transfusion hepatitis in the 1980s to vary between 2% and 31%. Rare cases of hepatitis B continue to occur despite donor screening for the hepatitis B surface antigen, but most are of the non-A, non-B type. Non-A, non-B hepatitis is typically mild and often subclinical in the acute phase but has a tendency to become chronic in about half the affected subjects. The recently characterised hepatitis C virus has been shown to cause most, if not all, transfusion associated non-A, non-B hepatitis. Hepatitis C seropositivity seems to be associated with viraemia and infectivity among blood donors, and donor screening for these antibodies has now been instituted in many countries. New assays now being developed are improving the sensitivity and specificity of this screening, which is estimated to prevent most cases perhaps 70 to 80% of post-transfusion hepatitis.     

Successful treatment of refractory ascites in a child with transjugular intrahepatic portosystemic shunt

A 16-y-old boy who had undergone bone marrow transplantation for relapsed acute lymphoblastic leukaemia developed liver cirrhosis and refractory ascites, which did not respond to salt restriction, diuretics and abdominal paracentesis. Liver transplantation was not feasible because of poor nutritional status, pre-existing renal dysfunction and uncertainty about the prognosis of his leukaemia. The patient underwent a successful transjugular intrahepatic portosystemic shunt (TIPS), with immediate resolution of ascites, enabling cessation of diuretics and improvement in nutritional status. At 24 mo following TIPS there has been no re-accumulation of ascites. CONCLUSION: TIPS may have a role in the management of refractory ascites secondary to liver cirrhosis in selected children.     

埋没导引缝合针在双侧唇裂继发畸形修复中的应用

目的　探讨双侧唇裂继发畸形的解剖学修复。方法　采用埋没导引缝合针缝合法 ,对于引起畸形的主要因素 :鼻翼软骨向两侧移位 ,鼻降肌挛缩 ,口轮匝肌移位 ,鼻孔底瘢痕挛缩等进行彻底松解后 ,牢固准确地复位、固定 ,以恢复其正常的解剖关系。结果　自 1998年以来 ,共收治 2 6例双侧唇裂继发畸形患者 ,除 1例叉状皮瓣远端坏死外 ,余均顺利成功。随访 1～ 2年效果满意。结论　本手术不仅简单省时 ,而且能达到从解剖学角度修复畸形