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Biomedical subjects

D J Fuller

Publications and source records attributed to D J Fuller.

At least 37 records · Page 2Linked to original sources
PubMed1983

Trigger wrist phenomenon in rheumatoid arthritis.

Flexor tendon synovitis in patients with rheumatoid arthritis commonly presents with a carpal tunnel syndrome and a concomitant trigger finger. Triggering at the wrist joint is in this disease an uncommon additional feature. In the two cases reported, histological examination of the tissue has indicated that, as well as chronic synovitis, there was a true rheumatoid nodule present at the wrist joint, either pedunculated or fusiform. The passage of the nodule, with a 'Click' from the proximal side of the transverse carpal ligament to the distal aspect, when the fingers are flexed, creates the sensation, signs and symptoms of a trigger wrist.

Arthritis, Rheumatoid↗
PubMed1983

Sensitization to heat by the polyamines and their analogs.

The polyamines putrescine, spermidine, and spermine have been shown to sensitize Chinese hamster ovary (CHO) cells to the cytotoxic effects of elevated temperatures. This sensitization occurs in the order spermine greater than spermidine greater than putrescine. A series of homologs of the diamine putrescine demonstrated little variance in the degree of potentiation until a chain length equivalent to that of spermidine was employed (1,8-diaminooctane). Two compounds bearing structural similarities to spermidine gave rather different results when combined with heat. Methylglyoxal bis(guanylhydrazone) (MGBG), an antiproliferative drug, sensitized cells to heat, while S-2-(3-aminopropylamino)-ethyl phosphoric acid (WR-2721), a radioprotector, had no measureable effect on 43 degrees C-induced cytotoxicity. Together, these results point out the primary importance of two terminal amino groups separated by either carbon, or carbon and nitrogen, atoms in an aliphatic chain in the observed sensitization of heat-induced cytotoxicity by polyamines. These data suggest specific dimensional characteristics of the presumed negatively charged structure(s) with which the polyamines are interacting to elicit this effect.

Amifostine↗
PubMed1983

Polyamines and polyamine biosynthesis in cells exposed to hyperthermia.

The issue of how polyamines act to sensitize cultured cells to the lethal effects of hyperthermia was investigated using Chinese hamster cells which were induced to express thermotolerance. Intracellular levels of these naturally occurring polycations were manipulated in certain situations by treating whole cells with methylglyoxal bis-(guanylhydrazone), an inhibitor of the S-adenosyl-L-methionine decarboxylases. Exogenous spermine as low as 100 microM in the culture media dramatically sensitized cells expressing thermotolerance to the lethal effects of subsequent 42 degrees C exposures. When thermotolerance was differentially induced in cultures exposed to 42.4 degrees C by varying the rate of heating from 37 to 42.4 degrees C, the most resistant cells had the highest levels of intracellular spermidine and spermine. This finding was explainable in part by the observation that the putrescine-dependent S-adenosyl-L-methionine decarboxylase activity was minimally affected in cells expressing the greatest degree of thermotolerance. When this enzyme activity was inhibited by drug, lowered intracellular polyamine levels did not correspond with subsequent survival responses to heat. Interestingly, cultures treated with methylglyoxal bis-(guanylhydrazone) 24 hr previous to heat exposure showed a reduced capacity to express rate of heating-induced thermotolerance. Together, these results demonstrate that the polyamines, especially spermidine and spermine, enhance hyperthermia-induced cell killing by some mechanism involving the plasma membrane. Further, our data suggest that methylglyoxal bis-(guanylhydrazone) can act to affect thermal responses by a mechanism(s) other than modification of intracellular polyamine levels.

Adenosylmethionine Decarboxylase↗
PubMed1982

Regional hip blockade in osteoarthrosis. Effects on pain perception.

Eighteen patients with unilateral osteoarthrosis of the hip were investigated in a trial which involved the injection of nine with bupivacaine and nine with normal saline. All the patients completed daily pain analogue charts. Their pain, mobility and functional activity were assessed and gait characteristics analysed, once before the injection and then at three monthly intervals. All the patients recorded a decrease in pain level within two weeks of injection, but it subsequently rose to pre-injection levels. There were no other significant general improvements after the injection. A significant increase in the maximum force at toe-off for the good leg was recorded one month after the injection. However, no further significant differences were found in the gait performance of either group of patients throughout the study. It is concluded that the hip nerve regional blockade offers no useful relief to the pain of osteoarthrosis of the hip joint.

Aged↗
PubMed1982

Malunited fractures of the forearm in children.

Malunion of fractures of the forearm in children can lead to permanent disability. The capacity of the radius and ulna to remodel spontaneously after malunion has been assessed in this study. Forty-nine children who had malunited fractures of the forearm were examined when the remodelling process was complete. It was noted that fractures of the distal third of the radius and ulna led to fewer problems than those of the diaphysis. It was concluded that malunion of the distal third of the radius and the ulna will remodel satisfactorily providing the child is less than 14 years of age. Gross malunion of the midshaft of the radius and ulna will spontaneously correct in an infant but little useful correction of deformity can be anticipated in diaphysial fractures when the child is aged eight years or more.

Adolescent↗
PubMed1982

Delayed sensitization to heat by inhibitors of polyamine-biosynthetic enzymes.

Exposure of Chinese hamster ovary cells to the enzyme inhibitors methylglyoxal bis(guanylhydrazone and alpha-difluoromethylornithine (DFMO) results in increased sensitivity to hyperthermia. While methylglyoxal bis(guanylhydrazone) demonstrates pronounced cytotoxicity at moderate extracellular concentrations, DFMO is tolerated well by this cell line at concentrations of up to 10 mM, as assayed by clonogenic survival after treatments at 37 degrees. An 8-hr preincubation at 37 degrees with either drug elicits increasing sensitivity to 43 degrees hyperthermia treatments with time after removal of the drug. In contrast to results obtained by heating in the presence of the drugs during the 8-hr exposure, DFMO acts as the more effective sensitizing agent for this delayed effect on progeny of DFMO-treated populations. This phenomenon seems to result from depletion of intracellular putrescine, because the effect can be at least partially recovered by providing the cells with an exogenous source of this diamine. The potential for in vivo heat sensitization by the non-toxic agent DFMO has yet to be investigated but may have intriguing clinical possibilities.

Animals↗
PubMed1980

Carbenicillin-trimethoprim/sulfamethoxazole versus carbenicillin-gentamicin as empiric therapy of infection in granulocytopenic patients. A prospective, randomized, double-blind study.

The results of therapy with carbenicillin plus trimethoprim-sulfamethoxazole (C-T/S) were compared to those obtained with carbenicillin plus gentamicin (C-G) in a prospective double-blind study of empiric antibiotic therapy in granulocytopenic patients. Patients were stratified into two groups: favorable-prognosis, group 1 (carcinoma, lymphoma, multiple myeloma), or unfavorable-prognosis, group 2 (acute leukemia, bone marrow transplantation), based on anticipated duration of granulocytopenia. Over-all, empiric antibiotic trials were more often successful (P = 0.004) in group 1 (55 of 62 patients or 89 per cent) than in group 2 (42 of 64 patients, 66 per cent)mwithin group 1, there was a favorable outcome in 30 of 32 (94 per cent) C-T/S trials and in 25 of 30 (83 per cent) C-G trials (P = 0.25); within group 2, there was a favorable outcome in 23 of 30 (77 per cent) C-T/S trials and in 19 of 34 (56 per cent) C-G trials (P = 0.14), Combined results in both groups indicated a higher proportion of favorable outcome in C-T/S trials (53 of 62, 85 per cent) than in C-G trials (44 of 64, 69 per cent). Further analysis (Manetl-Naenszel test) showed the over-all difference in outcome to be significant (P = 0.049), but the general applicability of this result may be limited by the rather low incidence of gram-negative bacterial infections in this study. There was no difference between the treatment regimens in antibiotic toxicity, and serious superinfection occurred only in group 2 patients (21 per cent of trials), equally divided between treatment arms. Initial protocol dosing achieved target plasma levels of trimethoprim (3 to 8 micrograms/ml) or gentamicin (4 to 10 micrograms/ml) in 57 of 68 (84 per cent) C-T/S trials compared to 21 of 60 (35 per cent) C-G trials.

Adult↗
PubMed1978

Specific regulation by steroid hormones of the amount of type I cyclic AMP-dependent protein kinase holoenzyme.

The total amounts of type I and type II cytoplasmic cyclic AMP-dependent protein kinase activities were measured in various tissues of intact rats and rats subjected to castration, hypophysectomy, or adrenalectomy. After castration, the total amount of type I activity decreased rapidly in classifically steroid-responsive tissues such as the ventral prostate and levator ani muscle and less rapidly in the liver. After hypophysectomy and adrenalectomy, type I activity in the liver decreased to the same extent as after castration. Type I activity could be maintained in the ventral prostate and levator ani muscle at control levels by the daily injection of dihydrotestosterone. Furthermore, after post-castration regression of the prostate for 3 days, three daily subcutaneous injections of dihydrotestosterone resulted in a complete restoration of type I activity toe the intact level. The amount of type II activity was not altered by any of the experimental ablations. This study provides evidence linking steroid action to the ability of steroid-responsive tissues to maintain a substantial activity of type I cyclic AMP-dependent protein kinase.

Adrenalectomy↗
PubMed1977

Cytoplasmic and nuclear protein kinases during the cell cycle.

Nuclear and cytoplasmic protein kinases were measured during the traverse of synchronous CHO cultures through G1 into S phase. Cells were synchronized by selective detachment of cells blocked in metaphase using colcemid. Nuclei were isolated and the protein kinases extracted from the nuclear preparation with 0.6 M NaCl. This procedure solubilized greater than 90% of the total protein kinase activity present in the nuclear preparation. DEAE chromatography of this extract showed 5 apparently different ionic forms of nuclear protein kinases. The nuclear protein kinases preferred casein and phosvitin to histone as substrates and were cyclic AMP-independent. Nuclear protein kinase activities increased greater than two-fold, when expressed as units of activity per cell nucleus, during G1 phase traverse, concomitant with a 70% increase in nuclear non-histone proteins (those soluble in 0.6 M NaCl). This resulted in only a 40% increase in the specific activities (units/microgram protein in 0.6 M NaCl extractable nuclear fraction) of these enzymes as cells progressed through G1 into S phase. This was in contrast to cytoplasmic cyclic AMP-dependent protein kinase activities which also increased two-fold during progression through G1 phase while total cellular protein increased less than 20%. Activation of, as well as synthesis of, cyclic AMP-dependent cytoplasmic protein kinases during G1 phase suggests a regulatory mechanism for precise temporal phosphorylation, whereas the constant specific activity in nuclear kinases during cell cycle is more compatible with the maintenance of bulk phosphorylation processes in the nucleus.

Cell Cycle↗
PubMed1977

Deoxyribonucleic acid and polyamine synthesis in rat ventral prostrate. Effects of age of the intact rat and androgen stimulation of the castrated rat with testosterone, 5 alpha-dihydrotestosterone and 5 alpha-androstane-3 beta, 17 beta-diol.

The relationship between polyamine synthesis, growth and secretion in vivo was examined in ventral prostates from: (a) intact rats aged 3-60 weeks; (b) animals castrated for 7 days before injection with 5 alpha-dihydrotestosterone (17 beta-hydroxy-5-alpha-androstan-3-one), testosterone and 5 alpha-androstane-3 beta, 17 beta-diol for up to 10 days; (c) rats injected with the 3 beta, 17 beta-diol immediately after castration. Ornithine decarboxylase activity and the concentrations of putrescine, spermidine and spermine were measured. DNA-synthetic activity was monitored by measuring [125I]iododoxyuridine incorporation. An enhanced spermidine/spermine molar ratio reflected increased activity of the prostate. The ratio was higher (greater than 2) in prostates from sexually immature animals, than in the intact adult (1.5), suggesting that the ratio was indicative of the proliferative activity of the tissue. However, in the androgen-stimulated castrated rat, enhanced spermidine/spermine ratios tended to correlate with hypertrophy and secretion. In both sets of experiments there was a linear relationship between protein and spermidine content. High spermidine/spermine molar ratios were the consequence of a relatively low rate of accumulation of spermine relative to spermidine and protein. The relationship between polyamine synthesis and DNA-synthetic activity was investigated in cultured prostate. A combination of insulin (3 mug/ml) and testosterone (0.1 muM caused a stimulatory response in the incorporation of [125I]iododeoxyuridine and in cell division, despite a depleted polyamine content and low ornithine decarboxylase activity in the cultured tissue.

Age Factors↗
PubMed1975

Initial effect of injury on ketone bodies and other blood metabolites.

The arterial and venous concentrations of ketone bodies and other metabolites were measured in twelve adults, from 2 to 24 hours after injury. Two groups could be distinguished, with or without hyperketonaemia (defined as more than 0.2 mmol per litre) in the 2-hour blood-sample. In the hyperdetonaemic group the concentrations of alanine, pyruvate, and lactate and the urinary nitrogen excretion were lower throughout the first 24 hours than in the non-hyperdetonaemic group. These preliminary results indicate that hyperketonaemia after trauma is associated with decreased protein breakdown.

Adolescent↗
PubMed1975

Ornithine decarboxylase activity and: [125I]iododeoxyuridine incorporation in rat prostate.

The relationship between ornithine decarboxylase activity and [125I]iododexyuridine incorporation was studied in prostates from castrated rats (aged 5, 26 and 80 weeks) injected daily with testosterone for up to 10 days. The results suggest that ornithine decarboxylase activity is a parameter of secretory activity, rather than growth, in the ventral prostate. In the dorsolateral prostate, ornithine decarboxylase activity tends to parallel [125I]iododeoxyuridine incorporation.

Animals↗