Community health services.

The Tomlinson report, with its emphasis on primary and community care, offers great scope to community health services, for long the poor relation of the NHS, and particularly poorly resourced in London. The aim is to create services that break down the barriers between primary, secondary, and tertiary health care and concentrate on providing high quality care tailored to individual patients'' needs. Thus a range of flexible options needs to be developed between acute hospital based care and the standard home care arrangements currently provided by district nurses. Examples, include hospital at home schemes, nursing beds, and rehabilitation beds. Together community and primary care services need to consider weekend coverage, to conduct research, and to become a setting for education. The infrastructure for primary and community care must, however, be put in place before acute facilities are shut.     

Biosynthesis of riboflavin. Enzymatic formation of 6,7-dimethyl-8-ribityllumazine from pentose phosphates

The xylene ring of riboflavin originates by dismutation of the precursor, 6,7-dimethyl-8-ribityllumazine. The formation of the latter compound requires a 4-carbon unit as the precursor of carbon atoms 6 alpha, 6, 7, and 7 alpha of the pyrazine ring. The formation of riboflavin from GTP and ribose phosphate by cell extract from Candida guilliermondii has been observed by Logvinenko et al. (Logvinenko, E. M., Shavlovsky, G. M., Zakal'sky, A. E., and Zakhodylo, I. V. (1982) Biokhimiya 47, 931-936). We have studied this enzyme reaction in closer detail using carbohydrate phosphates as substrates and synthetic 5-amino-6-ribitylamino-2,4-(1H,3H)-pyrimidinedione or its 5'-phosphate as cosubstrates. Several pentose phosphates and pentulose phosphates can serve as substrate for the formation of riboflavin with similar efficiency. The reaction requires Mg2+. Various samples of ribulose phosphate labeled with 14C or 13C have been prepared and used as enzyme substrates. Radioactivity was efficiently incorporated into riboflavin from [1-14C]ribulose phosphate, [3,5-14C]ribulose phosphate, and [5-14C]ribulose phosphate, but not from [4-14C]ribulose phosphate. Label from [1-13C]ribose 5-phosphate was incorporated into C6 and C8 alpha of riboflavin. [2,3,5-13C]Ribose 5-phosphate yielded riboflavin containing two contiguously labeled segments of three carbon atoms, namely 5a, 9a, 9 and 8, 7, 7 alpha. 5-Amino-6-[1'-14C] ribitylamino-2,4 (1H,3H)-pyrimidinedione transferred radioactivity exclusively to the ribityl side chain of riboflavin in the enzymatic reaction. It follows that the 4-carbon unit used for the biosynthesis of 6,7-dimethyl-8-ribityllumazine consists of the pentose carbon atoms 1, 2, 3, and 5 in agreement with earlier in vivo studies.     

The estimation of galactose, mannose and fucose in glycoproteins by radioisotope dilution

1. The principle of radioisotope dilution, as used previously for the estimation of mannose in egg albumin, was applied on a semi-micro scale to the estimation of fucose, mannose and galactose in some glycoproteins. The sugars were separated by partition chromatography on columns of Celite 545. 2. The release of mannose from egg albumin in 2n-hydrochloric acid at 100 degrees after various times was determined by the radioisotope-dilution method and found to have a half-time of 7min. 3. The destruction of mannose in 2n-hydrochloric acid after 3hr. at 100 degrees was found to be small if air was excluded. The destruction was slightly increased by the presence of lysozyme containing tryptophan in an amount equimolar with the mannose. The same amount of free tryptophan caused considerable loss of mannose. 4. Analytical values are reported for the non-amino sugar contents of egg albumin, rabbit gamma-globulin and some samples of blood-group-specific substances. The values found were similar to the most reliable estimates published previously.     

Immuno-isolation and culture of biliary epithelial cells from normal human liver

Summary Biliary epithelial cells (BEC) lining the intra-hepatic biliary ducts are the site of damage in several immunologically mediated liver diseases. BEC are difficult to isolate since they represent only 5% of the total cell number in normal liver. In this communication, a novel method for their isolation from normal liver is presented using a monoclonal antibody (HEA125) with specificity for an epithelial cell surface glyco-protein reported to be expressed in liver only by biliary epithelium. By combining differential density centrifugation and immuno-magnetic separation using HEA125 pure BEC (10⁵ cells/g fresh tissue) were prepared routinely. These cells were maintained in culture for up to 4 weeks with significant increases in cell numbers. The ability to prepare BEC from human liver offers an opportunity to develop In Vitro models to investigate the aetiology of diseases in intra-hepatic biliary epithelium. EDITOR’S STATEMENT This is a novel application to purification of specific liver cell types directly from tissue. It is well-suited for rapid communication because of its novelty and potential utility to investigators.     

Elective ventilation of potential organ donors.

Elective ventilation describes the procedure of transferring selected patients dying from rapidly progressive intracranial haemorrhage from general medical wards to intensive care units for a brief period of ventilation before confirmation of brain stem death and harvesting of organs. This approach in Exeter has led to a rate of kidney retrieval and transplant higher than has been achieved elsewhere in the United Kingdom, with a stabilisation of numbers on patients on dialysis. Recently doubt has been cast on the legality of our practice of elective ventilation on the grounds that relatives are not permitted to consent to treatment of an incompetent person when that treatment is not in the patient''s best interests. We are thus faced with the dilemma of a protocol that is ethical, practical, and operates for the greater good but which may be illegal. This article explores various objections to the protocol and calls for public, medical, and legal debate on the issues.