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Biomedical subjects

T Haga

Publications and source records attributed to T Haga.

At least 199 records · Page 11Linked to original sources

Adenylate cyclase permanently uncoupled from hormone receptors in a novel variant of S49 mouse lymphoma cells.

A novel variant of the S49 mouse lymphoma has been selected from wild-type cells by growth in medium containing the beta-adrenergic agonist terbutaline and inhibitors of cyclic nucleotide phosphodiesterase. In contrast to the situation in the wild-type clone, synthesis of adenosine 3':5'-monophosphate (cyclic AMP) is not stimulated by beta-adrenergic agonists or by prostaglandin E1 either in intact variant cells or in membrane preparations of such clones. However, basal and NaF-stimulated activities of adenylate cyclase [ATP pyrophosphate-lyase (cyclizine), EC 4.6.1.1] are normal, enzyme activity is stimulated by guanyl-5'-yl imidodiphosphate [Gpp(NH)p], and intact cells accumulate cyclic AMP when exposed to cholera toxin. Furthermore, variant cell membranes possess ligand-binding activity consistent with the conclusion that a normal or an excessive number of beta-adrenergic receptors is present. Thus, interaction between the hormone-binding and the catalytic moieties of the adenylate cyclase system is lost. This variant phenotype, designated as uncoupled (UNC), has been stable for more than 100 generations without exposure to the drugs used for selection. Such cells should be useful for the elucidation of methanisms of transmission of information from hormone receptors to adenylate cyclase.

Adenylyl Cyclases↗

Volar tenosynovectomy in the rheumatoid hand.

Rheumatoid involvement on the flexor aspect of the hand is common, but is easily overlooked because of difficulty in clinical examination. It is our experience that this localization of the disease process is extremely important and that surgical treatment should be given high priority. In this study a series of 235 operations on the flexor aspect of the hand performed on 139 patients are presented. The results are very gratifying as far as tenosynovectomy in the carpal tunnel and the pain is concerned. When performed on the fingers, however, varying degrees of postoperative flexion contractures developed in no less than 44%. It was found that this problem arose when the synovectomy was extended beyond the level of the middle flexion crease of the finger being caused by excessive postoperative scar formation in the region volar to the proximal interphalangeal joint between the tails of the superficial tendon. It is concluded that less extensive surgery should be aimed at in this particular area.

Aged↗

Microtubule formation from two components separated by gel filtration of a tubulin preparation.

(1) A tubulin preparation, purified by two cycles of polymerisation in 4 M glycerol, was further fractionated into two components by chromatography on a column of 6% agarose. One was a fraction of pure tubulin dimer devoid of any combination of high molecular weight ingredients (component T). The other was an aggregate of tubulin containing several minor ingredients (component N). (2) Microtubule formation from these two components was followed in a quantitative way by measuring flow birefringence (deltan). When component N was incubated at 37 degrees C, an instantaneous increase of delta n was observed even at a low concentration of protein, and the extent of polymerisation was roughly proportional to the protein concentration. With component T, the polymerisation occurred after a lag period, and only at a protein concentration higher than at least 0.5 mg/ml. Polymerisation of component T was greatly accelerated when a small amount of component N was added to the reaction medium. (3) Component N was dissociated into a tubulin dimer when the ionic strength of the medium was increased. On reducing the ionic strength, the dimer was reassociated to form the aggregate, which was again capable of accelerating polymerisation of component T. Minor ingredients contained in the component N were not completely removed during the course of its dissociation and reassociation. The dynein-like protein that was present in the component N, however, was no longer detectable in the reassociated aggregate.

Animals↗

Assessment of surgery of the rheumatoid wrist.

A series of 314 wrist operations performed on 227 patients with rheumatoid arthritis is presented. In 266 hands various wrist operations were undertaken with the object of synovial debridement and in 48 hands the wrist was also arthrodesed. The mean age at the time of surgical treatment was 51 years and the mean period of observation 4.2 years. This study shows that the main benefits of synovectomy are related to a constant and marked pain relief and prevention of tendon ruptures. The hope that synovectomy might arrest or prevent skeletal destruction was not realized and progression of X-ray changes was found in 74%. The very low recurrence rate in the present series as judged by clinical signs is probably not very significant and it is concluded that the X-ray findings are the most reliable criteria reflecting the real activity in a rheumatoid joint. In several wrists where prophylactic ulnar head resection had been performed through a small ulnar incision, an active dorsal tenosynovitis with tendon invasion developed later. These and other findings at the operation indicate that the erosive effect of the distal end of the ulna is certainly not the sole cause of tendon rupture in this area and that a complete exposure and decompression of the tendons should regularly be performed. Finally, arthrodesis of the wrist was so successful that it can be highly recommended.

Adolescent↗

Rapid transport of phosphatidylcholine occurring simultaneously with protein transport in the frog sciatic nerve.

1. Either l-[4,5-(3)H]leucine or [Me-(3)H]choline, or both l-[U-(14)C]leucine and [Me-(3)H]-choline, were injected into the ninth dorsal root ganglion of the frog, and peripheral transport of labelled proteins and/or phospholipids, mostly phosphatidylcholine, was studied by analysis of consecutive segments of the sciatic nerve. 2. At 25 degrees C, approx. 5% of the (3)H-labelled protein was transported at the rate of 152mm/day. The rate was temperature-dependent with the Q(10) value of 2.6. The flow was completely blocked by the local application of colchicine, but was unaffected by cytochalasin D. 3. [Me-(3)H]-Choline was incorporated into phosphatidylcholine at a comparatively slow rate, but was transported in the nerve at a rate equivalent to that for (3)H-labelled proteins. 4. The simultaneous transport of phosphatidylcholine and the protein was further supported in the double-labelling experiments by an identical transport rate of (3)H-labelled phosphatidylcholine and (14)C-labelled proteins, by their identical temperature dependence, by simultaneous blockade with colchicine, and also by the parallel distribution of the two labels in subcellular fractions. Specific radioactivities on a protein basis of both (3)H and (14)C labels were highest in microsomal subfractions enriched with Na(+)-plus-K(+)-stimulated adenosine triphosphatase and acetylcholinesterase. It is suggested that (3)H-labelled phosphatidylcholine and (14)C-labelled proteins transported in the nerve reside in the same structural entity, most probably a membrane component.

Acetylcholinesterase↗