Liver transplantation in 100 children: Cambridge and King's College Hospital series.

To review the results of the Addenbrooke''s and King''s College Hospital children''s liver transplantation programme.Retrospective analysis of the first 100 children to receive liver grafts at Addenbrooke''s Hospital, Cambridge, from December 1983 to March 1990.Addenbrooke''s Hospital, Cambridge, and King''s College Hospital, London.153 children assessed for liver transplantation, of whom 22 died before a donor became available and 31 were considered unsuitable. 100 children received grafts, of whom 27 had second grafts.One year actuarial patient survival was 71%, with 57% one year graft survival. In the last two years survival rates had improved considerably, with 86% of patients and 63% of grafts surviving for at least one year. Sixty five children were alive 12 to 86 months after transplantation; 63 were well and leading normal active lives and 56 had entirely normal liver function. Children''s growth and development were essentially normal, with many showing remarkable catch up growth.Liver transplantation offers children with terminal liver disease a high chance of a return to full quality life and normal development. Improved surgical and medical care have progressively improved survival. The timing of transplantation is critical but has been constrained particularly by the availability of donors and resources.     

Variability in host plant resistance of Sorghum to Striga Hermonthica infestation in West Africa

Fourteen elite sorghum lines were evaluated for their resistance to Striga hermonthica at three locations in Nigeria and Mali. Results showed that many of the lines especially MALISOR 84-1, SAMSORG 41, 97-SB-F5DT-64 (Keninkédié) and the check SRN 39 remained resistant to Striga in all locations with low emerged Striga counts, while SAMSORG 14 had the highest Striga infestation in all locations. Considerable variation in reaction to Striga infestation was observed on Séguètana, 97-SB-F5DT-63 (Wasa), 97-SB-F5DT-65, CMDT 38, CMDT 39 and CMDT 45 which were susceptible to Striga at Samaru, Nigeria but were resistant to Striga at both locations in Mali. Based on low Striga resistance and high grain yield, lines MALISOR 84-1, SAMSORG 41, 97-SB-F5DT-64, 97-SB-F5DT-65, CMDT 39 and SAMSORT 14 have been nominated for wider evaluation across more West African countries.     

Elongated mouse chromosomes suitable for enhanced molecular cytogenetics

Characterization of genetic disorders in humans and animal models requires identification of chromosomal aberrations. However, identifying fine deletions or insertion in metaphase chromosomes has been always a challenge due to limitations of resolution. In this study we developed a rapid method for chromosome elongation using two different intercalating agents: ethidium bromide and 5-bromo-2′-deoxyuridine (BrdU), together with a short-term mitotic block using colcemid. About 70% of the chromosomes from cells that underwent this elongation procedure reached three times longer than those prepared from control cells. FISH experiments using elongated chromosomes revealed a duplicated region of chromosome 11 that was not visible in cells prepared with conventional methods.     

Detection of drug-induced apoptosis and necrosis in human cervical carcinoma cells using 1H NMR spectroscopy

Apoptosis and necrosis need to be differentiated in order to distinguish drug-induced cell death from spontaneous cell death due to hypoxia. The ability to differentiate between these two modes of cell death, especially at an early stage in the process, could have a significant impact on accessing the outcome of anticancer drug therapy in the clinic. Nuclear magnetic resonance spectroscopy was used to distinguish apoptosis from necrosis in human cervical carcinoma (HeLa) cells. Apoptosis was induced by treatment with the topoisomerase II inhibitor etoposide, whereas necrosis was induced by the use of ethacrynic acid or cytochalasin B. We found that the intensity of the methylene resonance increases significantly as early as 6 h after the onset of apoptosis, but that no such changes occur during necrosis. The spectral intensity ratio of the methylene to methyl resonances also shows a high correlation with the percentage of apoptotic cells in the sample (r2=0.965, P<0.003).     

SOX10 mutations in chronic intestinal pseudo-obstruction suggest a complex physiopathological mechanism

The type IV Waardenburg syndrome (WS4), also referred to as Shah-Waardenburg syndrome or Waardenburg-Hirschsprung disease, is characterised by the association of Waardenburg features (WS, depigmentation and deafness) and the absence of enteric ganglia in the distal part of the intestine (Hirschsprung disease). Mutations in the EDN3, EDNRB, and SOX10 genes have been reported in this syndrome. Recently, a new SOX10 mutation was observed in a girl with a neural crest disorder without evidence of depigmentation, but with severe constipation due to a chronic intestinal pseudo-obstruction and persistence of enteric ganglia. To refine the nosology of WS, we studied patients with typical WS4 (including Hirschsprung disease) or with WS and intestinal pseudo-obstruction. We found three SOX10 mutations, one EDNRB and one EDN3 mutations in patients presenting with the classical form of WS4, and two SOX10 mutations in patients displaying chronic intestinal pseudo-obstruction and WS features. These results show that chronic intestinal pseudo-obstruction may be a manifestation associated with WS, and indicate that aganglionosis is not the only mechanism underlying the intestinal dysfunction of patients with SOX10 mutations.     

Anatomical basis of tolerance and immunity to intestinal antigens

The intestinal immune system has to discriminate between harmful and beneficial antigens. Although strong protective immunity is essential to prevent invasion by pathogens, equivalent responses against dietary proteins or commensal bacteria can lead to chronic disease. These responses are normally prevented by a complex interplay of regulatory mechanisms. This article reviews the unique aspects of the local microenvironment of the intestinal immune system and discuss how these promote the development of regulatory responses that ensure the maintenance of homeostasis in the gut.     

Surges of increased T cell reactivity to an encephalitogenic region of myelin proteolipid protein occur more often in patients with multiple sclerosis than in healthy subjects

We have previously shown that patients with multiple sclerosis (MS) have increased T cell responses to the immunodominant region (residues 184-209) of myelin proteolipid protein (PLP). The present study investigated whether this reactivity fluctuates over time and correlates with disease activity. We performed monthly limiting dilution assays for 12-16 mo in four healthy subjects and five patients with relapsing-remitting MS to quantify the frequencies of circulating T cells proliferating in response to PLP(41-58), PLP(184-199), PLP(190-209), myelin basic protein (MBP), MBP(82-100), and tetanus toxoid. Disease activity was monitored by clinical assessment and gadolinium-enhanced magnetic resonance imaging of the brain. There were fluctuations in the frequencies of autoreactive T cells in all subjects. Compared with healthy controls, MS patients had significantly more frequent surges of T cells reactive to the 184-209 region of PLP, but infrequent surges of T cell reactivity to MBP(82-100). There was temporal clustering of the surges of T cell reactivity to MBP(82-100) and MBP, suggesting T cell activation by environmental stimuli. Some clinical relapses were preceded by surges of T cell reactivity to PLP(184-209), and in one patient there was significant correlation between the frequency of T cells reactive to PLP(184-199) and the total number of gadolinium-enhancing magnetic resonance imaging lesions. However, other relapses were not associated with surges of T cell reactivity to the Ags tested. T cells reactive to PLP(184-209) may contribute to the development of some of the CNS lesions in MS.