Biomedical subjects
Publications and source records attributed to J Griffiths.
ALP is a profoundly ubiquitous enzyme that originates in many, if not all, mammalian tissues. The development of a simple ISEF technique has allowed reflection of at least 12 cellular components. Improvements in technique may add further zones of information. The aura of darkness surrounding ALP is being slowly dissipated.
Mononuclear cells were obtained from 42 patients with 'common variable' hypogammaglobulinaemia (CVH) and co-cultured with various cell lines in an attempt to isolate retroviruses. Cultures from only two patients showed evidence of a viral infection, although the virus could not be isolated and characterized in either. Despite the previous isolation of HIV's from two other CVH patients, this data suggests that similar viruses are not etiologically involved in the majority of patients.
We have developed an isoelectric focusing procedure for resolving alkaline phosphatase (EC 3.1.3.1) isoenzymes and isoforms in serum. We use a thin-layer agarose gel film containing synthetic carrier ampholytes and a "separator" to flatten the pH gradient in the region of the isoenzyme and isoform isoelectric points. Sharp, highly resolved zones of enzyme activity are obtained by limiting diffusion; for this we rapidly couple the released product, 1-naphthol, to a diazonium salt, which forms a colored precipitate at the site of activity. We have resolved and identified 12 zones of alkaline phosphatase activity in the serum of ostensibly healthy persons within a wide age range. Theoretically, three basic isoenzymes are produced from independent gene loci: intestinal, placental, and nonspecific tissue alkaline phosphatase. The other zones of activity may be isoforms.
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This paper describes a teaching programme, for use in general practice vocational training, which provides a theoretical and practical framework for exploring key aspects of the consultation with trainees. A particular emphasis is on the educational or 'cognitive' outcomes of the consultation and skills for improving them. The five stages of the programme are described and an example of experience of each stage is given. The paper concludes with an evaluation of the programme by the trainers, trainees and social scientist involved.
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Craniopharyngiomas in children are usually associated with growth retardation and hypogonadism. A patient with a craniopharyngioma treated with radiotherapy, who later developed isosexual precocious puberty, is described. She was treated with cyproterone acetate with a good clinical response. We suggest that craniopharyngiomas may become a more frequent cause of precocious puberty now that conservative therapy has been advocated for the condition.
Total plasma sialyltransferase (ST) activity was elevated in patients with colonic adenocarcinoma; the incidence of abnormal values ranged from 33% in patients with no evidence of metastases (T2N0M0) to 86% in patients with advanced metastatic disease (T2-5N1M1). Isoenzyme analysis revealed that normal serum contains a major band (ST2) probably derived from red cells, and a minor band (ST1) thought to be derived from platelets. An additional band, designated STN, intermediate in mobility between the two other bands, was found in patients with colonic adenocarcinoma, ranging in incidence from 50% to 86% in patients free of metastases and those with widespread metastases. Histological studies suggested that this abnormal isoenzyme was more likely to occur in the serum of patients whose tumor was well differentiated.
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We compared results by an enzyme-linked immunosorbent assay (ELISA) with those by a standard radioimmunoassay (RIA) for detection and quantitation of prostate-specific acid phosphatase (EC 3.1.3.2) in serum. Control subjects, patients with benign prostatic hyperplasia, and patients in all four clinical stages of prostatic adenocarcinoma were tested. The upper limit of normal (95% of the population) by the ELISA was 2.0 micrograms/L, and by the RIA was 2.2 micrograms/L. In prostatic adenocarcinoma stage I (not detectable by digital rectal examination), ELISA was slightly more sensitive than RIA, but sensitivity was still relatively low (20%). As tumor mass increased (stages II through IV), the frequency of increased concentrations of prostatic acid phosphatase in serum also increased. We confirmed this increase in circulating enzyme in some cases of benign prostatic hyperplasia and suggest that this finding is related to either acinar cytolysis or an increase in acini size and number. Although prostate-specific acid phosphatase is not a cancer-specific enzyme, we conclude that its measurement may be of considerable value in monitoring prostatic disease.
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The banding characteristics of an extreme variant familial chromosome 22 short-arm enlargement are described. Ag-AS staining for nucleolar-organizer regions, identified two areas of rDNA actively coding for 18S and 28S rRNA, the one being a broad distal Ag-band and the other a narrower centromeric Ag-band. The DNA in the major portion of the enlarged short arm was highly methylated, as shown by the binding of antibodies to 5-methylcytidine after UV-denaturation of chromosomal DNA. Mean Ag-band size on the aberrant 22p+ correlated with the mean number of 22p+ associations. Association of 22p+ was no greater than that of other acrocentrics, in spite of a presumed excess number of rDNA gene copies. This case represents only the second such normal variant defined by these techniques.
A stable isotope dilution assay for methylcitric acid in amniotic fluid was developed to provide rapid prenatal diagnosis of the inherited disorders propionic acidemia and methylmalonic acidemia. The method utilizes two 2H3-labeled diastereoisomers of methylcitric acid as internal standards, isolation by liquid partition chromatography and quantitation of the trimethyl esters by chemical ionization selected ion monitoring gas chromatography-mass spectrometry. Methylcitric acid at a concentration of 0.38 +/- 0.10 mumol/l was detected in normal amniotic fluid. Highly elevated levels of 7.87 and 9.16 mumol were found in the fluids surrounding fetuses affected with propionic acidemia and levels of 1.79, 2.72 and 12.27 mumol were found for fetuses with methylmalonic acidemia. Methylcitric acid was not elevated in the amniotic fluid of a fetus heterozygous for propionic acidemia. In the five pregnancies at risk for propionic acidemia, and three pregnancies at risk for methylmalonic acidemia, the levels of methylcitric acid in amniotic fluid gave the diagnosis in all cases. Measurement of methylcitric acid in amniotic fluid therefore provides a rapid and reliable method for the prenatal diagnosis of these genetic disorders.
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