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Biomedical subjects

D Shi

Publications and source records attributed to D Shi.

At least 91 records · Page 5Linked to original sources

Chronic NMDA receptor stimulation: therapeutic implications of its effect on adenosine A1 receptors.

It is known that stimulation of adenosine A1 receptors has a modulatory effect on the excitability of postsynaptic NMDA receptors. Conversely, acute stimulation of NMDA receptors results in release of adenosine via calcium-independent mechanisms. These findings indicate a close functional relationship between these receptors. It is, therefore, possible that chronic, low level stimulation of the NMDA receptor may have a negative impact on these modulatory processes. To investigate this possibility, we have subjected C57BL mice either to an acute injection of a N6-cyclopentyladenosine (CPA, 0.01 mg/kg) or deoxycoformycin (1 mg/kg) followed by a convulsant dose of N-methyl-D-aspartate (NMDA) (60 mg/kg) or to chronic, low level (20 mg/kg i.p. daily) exposure to NMDA for 8 weeks. One day after the last injection of NMDA, animals were injected either with a convulsant dose of NMDA alone, or with either CPA at 0.001 or 0.01 mg/kg, or with 1 mg/kg deoxycoformycin followed 15 min later by 60 mg/kg NMDA. Neither CPA nor deoxycoformycin were protective when NMDA was given acutely at 60 mg/kg. Chronic treatment with NMDA alone or chronic administration of NMDA followed by 0.001 mg/kg CPA had no significant effect on mortality following a convulsant dose of NMDA. However, when the chronic regimen of NMDA was followed by either 0.01 mg/kg CPA or 1 mg/kg deoxycoformycin, mortality was reduced to 10% (CPA), or eliminated completely (deoxycoformycin). Moreover, combination of chronic NMDA treatment with either CPA (both doses) or deoxycoformycin produced a significant improvement in other measures, i.e., seizure onset, intensity of neurological impairment, and extension of time to death.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗

Vein conduits for repair of nerves with a prolonged gap or in unfavourable conditions: an analysis of three failed cases.

Clinical failure of vein conduits for repair of four nerves in three cases is reported. Two digital nerves with gaps of 5.0 cm and 5.8 cm, respectively, and two median nerves with gaps of 4.0 cm and 5.0 cm were repaired with vein conduits. The digital nerves were repaired secondarily with insertion of nerve tissue slices. The median nerve lacerations were associated with compound soft tissue injuries and were repaired primarily by interfascicular vein conduits. There was no detectable recovery of sensibility in autonomous areas of these nerves and no sign of recovery of the innervated muscles during follow-up. Re-exploration revealed that the vein conduits used for repair of the median nerves were constricted by surrounding scar tissue and axon regeneration was precluded. The critical length for nerve regeneration in human beings and wound conditions unfavorable to nerve regeneration are discussed. This report suggests that vein conduits are not indicated in nerve gaps over 5.0 cm or in primary repair of nerves with compound injuries.

Adolescent↗

Preparation and analysis of large, flat crystals of Ca(2+)-ATPase for electron crystallography.

Obtaining large, flat, well ordered crystals represents the key to structure determination by electron crystallography. Multilamellar crystals of Ca(2+)-ATPase are a good candidate for this methodology, and we have optimized methods of crystallization and of preparation for cryoelectron microscopy. In particular, high concentrations of glycerol were found to prevent nucleation and to reduce stacking; thus, by seeding solutions containing 40% glycerol, we obtained thin crystals that were 5-30 microns in diameter and 2-10 unit cells thick. We found that removing vesicles and minimizing concentrations of divalent cations were critical to preparing flat crystals in the frozen-hydrated state. Finally, we developed two methods for determining the number of lamellae composing individual crystals, information that is required for structure determination of this crystal form. The first method, using low magnification images of freeze-dried crystals, is more practical in our case. Nevertheless, the alternative method, involving analysis of Laue zones from electron diffraction patterns of slightly tilted crystals, may be of general use in structure determination from thin, three-dimensional crystals.

Animals↗

Modified distal osteotomy of shortening the first metatarsal and for treatment of hallux valgus.

We evaluated the results of distal osteotomy of shortening the first metatarsal head with internal fixation of shape memory metal compression staple for hallux valgus in 26 feet of 17 women with a mean age of 41.0 years (30-65 years). The time for return to light work averaged 18.2 days, and to full work and normal walking 40.3 days after the operation. 16 patients (25 feet) had complete pain relief. Only in one foot, the pain was transferred under the 2nd metatarsal head. The appearance of the feet was markedly improved and the width of the forefeet was decreased by a mean of 0.92 cm after the operation. All of the patients were satisfied with the appearance of their feet. Radiographic analysis of feet showed that all osteotomies united, and the average angle of hallux valgus was improved from 30.1 degrees to 16.0 degrees, with the mean intermetatarsal angle of 11.2 degrees-6.5 degrees. No external fixation of plaster splintage was used and the distal fragment during healing of the osteotomy was stable. The time of bone healing was shortened and patients were allowed to bear weight at early stage.

Adult↗

The first report of echinococcus multilocularis in domestic dogs in Zhang County of Gansu Province.

In Zhang County of Gansu Province, 13 human cases of alveolar hydatid disease were reported up to 1990. However, the causative organism has not yet been described in animal hosts. In July 1990, postmortem examinations were made on 59 dogs (Canis familiaris) from the Caotan region of Zhang County. Of them, 6 were found to be infected with the adult worms of Echinococcus multilocularis. The morphological characteristics of the adult were compared in detail with those reported from different parts of China. Our adult specimens were closely resembling those of E. multilocularis reported from Ningxia. The role of domestic dogs in the epidemiology of alveolar echinococcosis in Zhang County was discussed.

Animals↗

[A study of proliferative activity of soft tissue sarcomas].

Proliferative activity of soft tissue sarcomas (STS) in 31 cases was examined by histologic grading, mitotic count, DNA analysis by flow cytometry, and immunohistochemical procedures with monoclonal antibody Ki-67. Aneuploid was found in 12 of 16 cases (75.0%) with Grade 3, and in 4 of 15 cases (26.7%) with Grade 1,2 (P = 0.0121). Tumors with more than 100 Ki-67 positive cells per 10 high power fields (HPF) had a higher rate of aneuploid (81.3%) than those with less than 100 Ki-67 per 10 HPF (26.7%) (P = 0.0038). There was significant correlation between Grade and DNA index (DI) (r = 0.4901, P = 0.0051), Grade and Ki-67 (r = 0.4636, P = 0.0086), Ki-67 and DI (r = 0.6368, P = 0.0001). The results indicate that DI and reactivity of tumor cells to Ki-67 may reflect proliferative activity and be helpful for clinicians to judge the biological behaviour of tumors more accurately and objectively. Hence, supplementary to the grading of STS, DI and Ki-67 score could be useful as prognostic parameters for clinical invetigation of multimodality therapy for individual patients.

Adolescent↗

[Flexor tendon repair: timing of surgery and sheath management].

Effect of timing of repair and management of sheath on functions of injuried tendons was evaluated in a clinical relevant model using 60 white leghorn chickens. The flexor digitorum profundus (FDP) tendons of the long toes were cut and were repaired at 1, 4, 8, 14 and 20 days after injury. The sheath on the left foot was closed and that on the right excised. The tendon excursion, toe motion, morphology of the sheath and tendon healing were studied 6 weeks after tendon repair. Tendon functions were the best in primary repair, and they got worse as the delay became longer. Repair in the late stage produced significantly worse tendon functions. Sheath closure with remarkable tension worsened tendon healing. We conclude that the optimal timing for tendon repair is at the primary stage. Delayed tendon repair can be performed within 3 weeks to one month after injury, but the repair is preferably done in initial several days of delay. Direct sheath closure is not advocated in tendon repair in the delayed period.

Animals↗

Chronic effects of ethanol on central adenosine function of mice.

Chronic ingestion of 5% ethanol had no significant effect on open field locomotor of NIH Swiss strain male mice, nor were the depressant effects of a non-selective adenosine receptor agonist, NECA, or the stimulant effects of a non-selective antagonist, caffeine significantly altered. The density of cerebral cortical A1-adenosine receptors and of nitrendipine binding sites on calcium channels were significantly increased after chronic ethanol, while the density of striatal A2a-adenosine receptors were unchanged. The locomotor stimulant effects of ethanol (2.5 g/kg) were slightly decreased after chronic ethanol, but were markedly reduced in mice after chronic caffeine ingestion. The results suggest some involvement of adenosine systems in the effects of ethanol.

Adenosine↗

Inhibition of platelet aggregation by adenosine receptor agonists.

2-(Ar)alkoxyadenosines, which are agonists selective for the A2AAR in PC 12 cell and rat striatum membranes, are also agonists at the A2AR coupled to adenylate cyclase (AC) that mediates the inhibition of platelet aggregation. A panel of twelve well-characterized adenosine analogues stimulated human platelet AC and inhibited ADP-induced platelet aggregation at sub- to low-micromolar concentrations with a potency ranking CGS 21680 > adenosine > R-PIA. There were significant correlations between the EC50 of anti-aggregatory activity and either the EC50 of stimulation of platelet and PC 12 cell AC (r2 = 0.66 and 0.67, respectively) or the Ki of inhibition of [3H]NECA binding to the rat striatum membranes (r2 = 0.75). Likewise, platelet AC stimulation correlated well with stimulation of PC 12 cell AC and with [3H]NECA binding (r2 = 0.94 and 0.91, respectively). Ten 2-(ar)alkoxyadenosines stimulated platelet AC at EC50s ranging between 0.16 and 2.3 microM and inhibited platelet aggregation at EC50s ranging between 2 and 30 microM. There were no correlations between the EC50s of anti-aggregatory activity and either the EC50s of the stimulation of platelet or PC 12 AC (r2 = 0.08 and 0.06, respectively) or with the Ki of the inhibition of [3H]NECA binding to the A2aAR in rat striatum (r2 = 0.02). The EC50s of the stimulation of platelet AC correlated with those of the stimulation of PC 12 AC (r2 = 0.48), and also with the Ki of [3H]NECA binding (r2 = 0.71). Each of the 23 adenosines completely inhibited platelet aggregation and thus, functionally, all behaved as full agonists.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗

Double and multiple looped suture tendon repair.

We report our experience of using double or multiple looped sutures for primary tenorrhaphy combined with early active mobilization. In 46 patients involving 51 fingers with flexor tendon lacerations, double threads of the looped nylon suture were placed to repair injured FDP or FDS tendons, or three threads of looped nylon suture were made to repair the FDP tendons. Using White's (1956) criteria, the results were good or excellent in 76.5% of fingers. The double and multiple looped sutures are of sufficient strength to sustain early motion, and cause little disturbance in the circulation. Satisfactory function following primary tendon repair can be expected with these new techniques.

Adolescent↗

[Classification of hand and its significance].

Measurements of normal values in hand appearance and thumb movements were done in 102 male adult volunteers with no history of previous injury to their hands. The data showed some characteristics between the appearance and function of hand, for example, no case showed the distance of adduction of thumb was 0, but the normal function of hand was still acquired. Positive correlation appeared between the indexes of appearances of hand. Correlation analysis have been done for three pairs of indexes, that is, hand length and width, length of thumb and the distance of first web, adduction of thumb and thumb-opposition. The correlation charts and their formulae have been presented. Furthermore, hands of male chinese could be classified into five types according to the correlation chart or the formula. The significance of such classification i discussed as well.

Adult↗

A role for central A3-adenosine receptors. Mediation of behavioral depressant effects.

The behavioral effects of a selective A3 adenosine receptor agonist 3-IB-MECA (N6-(3-iodobenzyl)-5'-N-methylcarboxamidoadenosine) in mice and the localization of radioligand binding sites in mouse brain were examined. Low levels of A3 adenosine receptors were detected in various regions of the mouse brain (hippocampus, cortex, cerebellum, striatum), using a radioiodinated, high-affinity A3-agonist radioligand [125I]AB-MECA (N6-(3-iodo-4-aminobenzyl)-5'-N-methylcarboxamidoadenosine). Scatchard analysis in the cerebellum showed that the Kd value for binding to A3 receptors was 1.39 +/- 0.04 nM with a Bmax of 14.8 +/- 2.1 fmol/mg protein. 3-IB-MECA at 0.1 mg/kg i.p. was a locomotor depressant with > 50% reduction in activity. Although selective A1 or A2a antagonists reversed locomotor depression elicited by selective A1 or A2a agonists, respectively, the behavioral depressant effects of 3-IB-MECA were unaffected. 3-IB-MECA also caused scratching in mice, which was prevented by coadministration of the histamine antagonist cyproheptadine. The demonstration of a marked behavioral effect of A3 receptor activation suggests that the A3 receptor represents a potential new therapeutic target.

Adenosine↗

Reexpression of neu-encoded oncoprotein counteracts the tumor-suppressing but not the metastasis-suppressing function of E1A.

By transfecting the adenovirus 5 E1A gene into neu-transformed NIH3T3 cells, we previously showed that E1A can dramatically repress neu-encoded p185 expression and, concomitantly, suppress the features of transformation and metastasis of neu+E1A transfectants. From these results we concluded that suppression of transformation and metastasis by E1A in neu-transformed cells may be through repression of neu gene expression. However, E1A has recently been shown to also repress the transformation features of other human cancer cells that do not overexpress neu. This observation raised a possibility that repression of neu gene expression in our neu+E1A cells might not be the only mechanism for transformation and metastasis suppression. To study whether other molecular mechanisms might be involved in suppression of transformation and metastasis by E1A in our neu+E1A cells, we reexpressed p185 oncoprotein in the neu+E1A cells by transfecting them with a plasmid containing activated rat neu complementary DNA and we examined whether E1A can suppress transformation and metastasis when the neu-encoded p185 protein is reexpressed. All the features of transformed cells including cell morphology, DNA synthesis rate, colony formation in soft agar, and tumorigenicity in nu/nu mice were restored in the cell lines that reexpressed neu. In addition, the levels of neu reexpression corresponded to the degree of malignant transformation. However, the in vivo metastatic tumor formation by these p185 reexpressing cells was still significantly inhibited by E1A. When metastasis-associated properties were examined in the cell lines that reexpressed p185, we found that cell motility was recovered by reexpression of p185 to the degree corresponding to the p185 reexpression level, but secretion of membrane-degrading gelatinases and invasion through the basement membrane preparation Matrigel by these cells were still inhibited by E1A. The data demonstrated that reexpression of p185 in neu+E1A cells can counteract the tumor-suppressing function of E1A but not completely recover the neu-induced metastatic phenotype. We conclude from these results that (a) repression of neu oncogene expression was indeed the molecular mechanism by which E1A suppressed tumor formation in neu-transformed 3T3 cells, and (b) suppression of metastasis by E1A in neu-transformed 3T3 cells was via multiple molecular mechanisms in addition to repressing neu. Our model system clearly demonstrated that tumorigenicity and metastasis are related but separable phenomena.

3T3 Cells↗

Synthesis of paraxanthine analogs (1,7-disubstituted xanthines) and other xanthines unsubstituted at the 3-position: structure-activity relationships at adenosine receptors.

Synthetic procedures for the preparation of various 3-unsubstituted xanthines, including paraxanthine analogs (1,7-disubstituted xanthines) and 1,8-disubstituted xanthines, were developed. Silylation of 1-substituted xanthines followed by alkylation at the 7-position provides a facile route to paraxanthine analogs. Regioselective alkylation of tris(trimethylsilyl)-6-aminouracil provides 3-substituted 6-aminouracils, which are converted to 1,8-disubstituted xanthines by standard procedures. The ring closure of 3-substituted 5-cyclopentanecarboxamido- and 5-(benzoylamino)-6-aminouracils requires drastic reaction conditions. Affinity for brain A1 and A2 adenosine receptors was determined in binding assays for these and other xanthines with substituents in 1-, 3-, 7-, 8-, and 9-positions. Substitution at the 1-position was necessary for high affinity at adenosine receptors. 1,3-Disubstituted xanthines generally had higher affinity than 1,7-disubstituted xanthines. 1,8-Disubstituted xanthines had high affinity for adenosine receptors; some were highly selective for A1 receptors.

Animals↗