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Biomedical subjects

D J Adamson

Publications and source records attributed to D J Adamson.

At least 19 recordsLinked to original sources
PubMed1999

Imaging of the thorax in the management of germ cell testicular tumours.

AIM: To evaluate role of chest computed tomography (CTC) and chest radiography (CXR) in management of patients with testicular germ cell tumours (GCT). PATIENTS AND METHODS: An analysis was undertaken of staging and re-assessment CTC and CXR examinations performed on patients with GCT over a 4.5-year period. Data were obtained on clinical presentation, tumour histology, tumour marker levels and clinical course. Consensus review interpretation was combined with these data to obtain a 'standard of reference'. Sensitivity, specificity and predictive values were derived by comparison of original imaging reports to 'standard of reference'. RESULTS: Six hundred and twenty-three CTC examinations on 207 patients with GCT were included. Intrathoracic metastases were identified in 1% of seminoma patients compared with 20% of non-seminoma (NSGCT) patients. CTC was more accurate than CXR in the detection of intrathoracic metastases at 0.97, 0.96-0.98 (95% CI) compared with 0.91, 0.89-0.93. The agreement between imaging techniques and the standard of reference (determined by Kappa statistic) was respectively 0.96 for CTC and 0.65 for CXR. In GCT patients undergoing re-assessment with both CXR and CTC, CXR never detected unknown intrathoracic metastatic disease. Abdominopelvic lymphadenopathy was associated with intrathoracic metastases (P < 0.001), however re-assessment CTC did identify intrathoracic metastases in 27 cases without concurrent abdominopelvic disease. CXR was negative in 19 of these. CONCLUSION: Routine interval CXRs are unnecessary in NSGCT patients undergoing regular re-assessment CTC due to the low additional yield and limited effect on management. Re-assessment should still include CTC. In low risk, pure seminoma patients (abdominal CT and marker negative) re-assessment CTC can be safely avoided. Baseline CTC is advocated with CXR alone for re-assessment.

False Negative Reactions↗
PubMed1996

Effect of three different warm-up regimens on heat balance and oxygen consumption of thoroughbred horses.

Horses were exercised at 105% of their maximal O2 uptake until fatigued after three different warm-up regimens (no warm-up, a light warm-up, and a warm-up until the central venous temperature was > 39.5 degrees C) to assess the effect of the warm-up on the various avenues of heat loss. Approximately 12.79, 15.10, and 18.40 MJ of heat were generated in response to the warm-up and exercise after the three different warm-up regimens, respectively. Of the heat generated, 17.5, 17.2, and 17.4% remained as stored heat after 20 min of active recovery. Heat loss from the respiratory system was 63.6, 33.7, and 40.3% of the heat produced during and after the three warm-up intensities, respectively. The balance of the heat loss was assumed to be via the evaporation of sweat. On this basis, the heat loss by sweating was 14.9, 49.1, and 42.3% of the heat produced during and after the three warm-up intensities, which represented evaporation of 0.8, 3.1, and 3.0 liters of sweat, respectively. O2 consumption during exercise and heart rates 20 min postexercise, after two of the warm-up regimens, was significantly lower than that after no prior warm-up.

Animals↗
PubMed1995

p53 mutation and expression in lymphoma.

Mutation and abnormal expression of p53 was studied in 38 lymphomas [five Hodgkin's disease and 33 non-Hodgkin's lymphoma (NHL)]. CM1 polyclonal antibody was used to detect overexpression of p53. Three missense mutations were characterised in three cases of NHL after screening exons 5-8 of p53 of all the tumours with single-strand conformation polymorphism (SSCP) analysis. Only two out of three tumours with a missense mutation showed abnormal expression of p53 as measured by CM1. Conversely, seven out of nine tumours with positive CM1 staining had no point mutation demonstrated. Overexpression of p53 in the cases of NHL occurred in three out of twenty four low-grade tumours and five out of nine high-grade tumours (Kiel classification). The results suggest that abnormalities of p53 are commoner in high-grade than low-grade NHL, and that positive immunocytochemistry cannot be used to determine which tumours have mutations of p53.

Adult↗
PubMed1995

p53 mutation in the myelodysplastic syndromes.

We have studied point mutations in exons 5-8 of the p53 gene in the myelodysplastic syndromes (MDS) by using polymerase chain reaction (PCR) single-strand conformation polymorphism (SSCP) analysis and direct nucleotide sequencing. The subtypes examined were: refractory anaemia (RA), refractory anaemia with ring sideroblasts (RARS), chronic myelomonocytic leukaemia (CMML), refractory anaemia with excess blasts (RAEB), refractory anaemia with excess blasts in transformation (RAEBt), and acute myeloid leukaemia (AML) which had evolved from MDS. 26 cases of MDS were studied. 12 of these were sequentially sampled but none changed its p53 status during the time of the study (18 months). Four mutations (one nonsense and three missense) were identified. Each case with a mutation was of an advanced MDS subtype, suggesting that p53 mutation in these diseases is a terminal genetic event in the process of leukaemogenesis. The nonsense mutation inserted a premature stop codon in a case of AML which had evolved from RAEB; this mutation has been reported before in both chronic myeloid leukaemia (CML) and Burkitt's lymphoma. The three missense mutations have not previously been reported in haematological malignancies.

Acute Disease↗
PubMed1993

Gas-forming infections.

A 89 year old woman was admitted with increasing confusion and difficulty in walking. Her left thigh was swollen, erythematous and had associated crepitus.

Aged↗
PubMed1992

Significant telomere shortening in childhood leukemia.

Telomere length was studied by Southern analysis in five cases of childhood acute leukemia. In four cases, the length of the telomere sequence of the blast phase cells was shortened as compared with that of the cells examined during remission. Study of telomere length during chemotherapy for hematologic malignancies may show rapidly dividing subpopulations of malignant cells and thereby guide further treatment needs. In addition, such loss of telomere sequence would give rise to chromosomal instability and could be one of the mechanisms of oncogene activation in acute leukemia.

Blotting, Southern↗
PubMed1992

Alcoholism, hyponatraemia and central neurological damage: more than pontine myelinolysis?

Three patients with alcoholism and severe hyponatraemia are described. Permanent neurological damage occurred in each case with cerebral, cerebellar or pontine damage from infarction or haemorrhage following correction of the biochemical disturbance. No patient developed Central Pontine Myelinolysis (CPM), the condition usually associated with profound hyponatraemia and its correction.

Adult↗
PubMed1991

Reversible infertility and Castleman's disease.

Castleman's disease may cause systemic symptoms with biochemical and haematological disturbances (Featherstone et al. 1990). These usually resolve completely soon after surgical removal of the abnormal mass. We report two cases of infertility associated with the systemic disturbances of abdominal Castleman's disease. Both women conceived less than one year after removal of the 'tumour' and delivered normal infants.

Abortion, Habitual↗
PubMed1988

Nitrosoureido nucleosides as potential inhibitors of nucleotide biosynthesis.

Several nitrosoureido nucleosides (3a, 3b, 5a, 7a, 7c, and 10a) designed as inhibitors of enzymes that metabolize pyrimidine nucleotides have been prepared and their chemical and biological properties studied. The methylnitrosoureas 3a and 3b were not significantly cytotoxic to H.Ep.-2 and L1210 cells in vitro but showed moderate activity in the P388 mouse leukemia screen (79% ILS for 3a and 56% ILS for 3b). The (chloroethyl)nitrosoureas 7a and 7c inhibited proliferation of L1210 cells, were cytotoxic to H.Ep.-2 cells, and demonstrated good activity against P388 in vivo (135% ILS with one 30-day survivor for 7a and 191% ILS with two 30-day survivors for 7c). Overnight exposure of L1210 cells to 7a and 7c resulted in cell enlargement accompanied by cell lysis. Macromolecular synthesis in enlarged cells, particularly RNA and protein synthesis, was markedly increased relative to that in untreated control cells. The half-lives of each of the nitrosoureas in pH 7 buffer was determined and compared with biological activity.

Animals↗
PubMed1985

Metabolism and metabolic effects of 2-azahypoxanthine and 2-azaadenosine.

The metabolism and metabolic effects of 2-azahypoxanthine and 2-azaadenosine were studied to elucidate the biochemical basis for their known cytotoxicities. 2-Azaadenosine is a known substrate for adenosine kinase. That 2-azahypoxanthine is a substrate for hypoxanthine (guanine) phosphoribosyltransferase is shown by the observations that, in cell-free fractions from HEp-2 cells supplemented with 5-phosphoribosyl-1-pyrophosphate, 2-azahypoxanthine inhibited the conversion of hypoxanthine to IMP but not the conversion of adenine to AMP, and hypoxanthine, but not adenine, inhibited the conversion of 2-azahypoxanthine to 2-azaIMP. [8-14C]2-Azahypoxanthine was synthesized from [8-14C]hypoxanthine via [2-14C]-4-amino-5-imidazolecarboxamide. In HEp-2 cells in culture, the principal metabolite of [8-14C]-2-azahypoxanthine was 2-azaATP; there was no detectable 14C in deoxynucleotides or in DNA or RNA fractions. 2-Azaadenosine was much more toxic than 2-azahypoxanthine, and, when used in the presence of an adenosine deaminase inhibitor, 2'-deoxycoformycin, was converted in HEp-2 cells to 2-azaATP in amounts that exceeded those of ATP in control cells. The pool of ATP was reduced by as much as 75% as 2-azaATP accumulated. In a short-term experiment (4 hr), 2-azaadenosine selectively reduced the pools of adenine nucleotides, whereas 2-azahypoxanthine reduced the pools of guanine nucleotides selectively. Both 2-azahypoxanthine and 2-azaadenosine inhibited the incorporation of formate into purine nucleotides and were without effect on the conversion of thymidine and uridine to nucleotides. 2-Azahypoxanthine inhibited the incorporation of thymidine into macro-molecules but not that of uridine or leucine; 2-azaadenosine inhibited the incorporation of all three of these precursors non-selectively. 2-AzaIMP inhibited IMP dehydrogenase competitively with IMP (Ki = 66 microM). The difference in effects of 2-azahypoxanthine and 2-azaadenosine perhaps may be due to the production, from 2-azahypoxanthine but not from 2-azaadenosine + 2'-deoxycoformycin, of 2-azaIMP, which inhibits synthesis of guanine nucleotides and thereby results in inhibition of DNA synthesis. Specific sites of action for 2-azaadenosine are yet undefined.

Adenosine↗
PubMed1984

Chemical properties and biological effects of 2-haloethyl sulfonates.

Data for the alkylating activities, DNA cross-linking activities, and proliferation-inhibitory activities toward cultured L1210 cells for twenty-four 2-haloethyl sulfonates are reported. Previously reported activities against P388 leukemia in vivo are also presented to permit correlation of in vitro and in vivo properties. Since these compounds are believed to be 2-haloethylating agents, their properties and effects were compared with those of chlorozotocin, which is a recognized 2-chloroethylating agent. 2-Chloroethyl chloromethanesulfonate, which was the most effective compound against P388 leukemia, had a moderate level of alkylating activity and a low level of cross-linking activity, but it was quite active in inhibiting proliferation of cultured L1210 cells. Although its alkylating activity was about the same as that of chlorozotocin, it caused much less cross-linking of DNA. The in vitro tests were useful for gaining information relating structure to the individual properties, but results obtained for one of the properties might not be predictive of the relative values obtained for other properties nor for in vivo activity against P388 leukemia. These results indicate that additional experiments to define the mechanism of action of these agents are needed.

Alkanesulfonates↗
PubMed1984

Mode of action of 2-amino-6-chloro-1-deazapurine.

2-Amino-6-chloro-1-deazapurine is of interest as a purine analog with demonstrated in vivo activity against mouse leukemia L1210. That the active form of this agent is a nucleotide and that the nucleotide is formed by the action of hypoxanthine (guanine) phosphoribosyltransferase were shown by the facts that (a) L1210 cells deficient in hypoxanthine phosphoribosyltransferase were insensitive to the analog; (b) hypoxanthine, but not adenine, prevented the formation of the analog nucleotide by enzyme preparations containing activities of both hypoxanthine and adenine phosphoribosyltransferases; and (c) the cytotoxicity of the analog was prevented by hypoxanthine. The ribonucleoside of this analog was not toxic to cell cultures and hence is not phosphorylated or cleaved to the base. In intact HEp-2 cells and L1210 cells, the analog was metabolized to the nucleoside 5'-phosphate which accumulated to concentrations as high as 1000 nmoles/10(9) cells; no di- or triphosphates were detected. In HEp-2 cells, the analog reduced the pools of purine nucleotides with some accumulation of IMP. The toxicity of minimal inhibitory concentrations of the analog to HEp-2 cells could be prevented or reversed by 4(5)-amino-5(4)-imidazolecarboxamide (AIC); the toxicity of higher concentrations could be prevented or reversed by a combination of adenine and guanosine but not by AIC. The analog inhibited the incorporation of formate into purine nucleotides and into macromolecules at concentrations that had no effect on utilization of hypoxanthine; at higher concentrations the incorporation of hypoxanthine was inhibited. Low concentrations also inhibited the utilization of uridine and thymidine. The incorporation of hypoxanthine and AIC into guanine nucleotides, but not adenine nucleotides, was inhibited. These results indicate two sites of inhibition of the biosynthesis of purine nucleotides, the more sensitive one being on an early step of the pathway and the less sensitive one on the IMP-GMP conversion. That the blockade of de novo synthesis probably was at the site of feedback inhibition was indicated by the fact that the analog inhibited the accumulation of formylglycinamide ribonucleotide in azaserine-treated cells but did not inhibit the synthesis of 5'-phosphoribosyl 1-pyrophosphate. Comparative studies were performed with the related analog, 2-amino-6-chloropurine, which has been reported to produce a similar dual blockade of the purine pathway. This purine was less toxic than its 1-deaza analog; it produced a modest decrease in adenine nucleotides but increased pools of guanine nucleotides.(ABSTRACT TRUNCATED AT 400 WORDS)

2-Aminopurine↗