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11.
G R Girard W E Bondinell L M Hillegass K G Holden R G Pendleton I Uzinskas 《Journal of medicinal chemistry》1989,32(7):1566-1571
A series of 7,8-fused heterocyclic tetrahydroisoquinolines were synthesized and tested as inhibitors of rabbit adrenal phenylethanolamine-N-methyltransferase (PNMT). 6,7,8,9-Tetrahydro[1,2,3]thiadiazolo[5,4-h]isoquinoline 5 (SK&F 86607) was found to be a potent inhibitor of PNMT with an IC50 similar to that of 7,8-dichloro-1,2,3,4-tetrahydroisoquinoline (1, SK&F 64139). The isomeric tetrahydro[1,2,3]thiadiazolo[4,5-h]- and tetrahydro[1,2,5]thiadiazolo[3,4-h]isoquinolines, 13 and 20, were also potent PNMT inhibitors. However, substitution of Cl at position 5 (17) resulted in loss of potency similar to the loss observed in the 5-chloro analogue of 1. The 1,2,5 isomer 20 showed only a small drop in activity at 10(-6) M. All of the thiadiazoles were more potent than the 7,8-benzo-fused analogue 36. Fusion of other five-membered heterocyclic ring systems at the 7,8-position, e.g. triazole 22 and imidazoles 24 and 26, resulted in a decrease of PNMT inhibition. The alpha-adrenoreceptor affinities of 1 and 5 were also compared. 相似文献
12.
A. TSATSOULIS E. WHITEHEAD J. ST. JOHN S. M. SHALET W. R. ROBERTSON 《Clinical endocrinology》1987,27(6):683-689
Eighteen men (mean age 27, range 18-30 years) treated for Hodgkin's disease with 6-8 courses of MVPP (Mustine, Vinblastine, Procarbazine and Prednisolone) have had Leydig cell function assessed by their steroidogenic responses to stimulation by a single bolus dose of HCG (1000 units intramuscularly). Normal age-matched men (n = 16) acted as controls. Baseline immunoreactive FSH was markedly raised in the patients (mean 18.1 +/- SD 6.9 vs 2.0 +/- 1.5 IU/l, P less than 0.0001) reflecting damage to the germinal epithelium. Immunoreactive LH was also greater in patients (10.3 +/- 3.9 IU/l) than in controls (3.9 +/- 1.9 IU/l, P less than 0.0001). There were no differences between the baseline testosterone, androstenedione, oestradiol, oestrone and sex hormone binding globulin (SHBG) concentrations. The testosterone/SHBG ratios were similar in the two groups and there was no correlation between baseline LH and testosterone concentrations or testosterone/SHBG ratios. Testosterone, androstenedione, oestradiol and oestrone secretion in response to HCG stimulation were similar at 24 h and 96 h in both groups. In order to explain the paradox of elevated immunoreactive LH in the face of normal testicular steroidogenesis in such patients, LH biological activity (B) as well as LH immunoreactivity (I) and FSH and testosterone were estimated in a second similar group of patients (n = 17, mean age 27, range 17-43 years) and in a further age-matched control group (n = 17). Bioactive and immunoreactive LH levels were significantly increased (P less than 0.005 and P less than 0.001, respectively) in the patient group.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
13.
G A Dienel N F Cruz K Mori J E Holden L Sokoloff 《Journal of cerebral blood flow and metabolism》1991,11(1):25-34
Steady-state distribution spaces of 2-[14C]deoxyglucose ([14C]DG), glucose, and 3-O-[14C]methylglucose at various concentrations of glucose in brain and plasma ranging from hypoglycemic to hyperglycemic levels have been determined by direct chemical analyses in the brains of conscious rats. The hexose concentrations were measured chemically in freeze-blown brain extracted with ethanol to avoid the degradation of acid-labile products of [14C]DG back to free [14C]DG that has been found to occur with the more commonly used perchloric acid extraction of brain. Corrections were also made for nonphosphorylatable, labeled products of [14C]DG found in the nonacidic fractions of the brain extracts, which were previously included with the assayed [14C]DG, and for the contribution of the hexose contents in the blood in the brain, which was found to be particularly critical for the determination of the glucose distribution space, especially in hypoglycemic states. From the measured contents of the hexoses in brain and plasma, the relationships of the tissue concentrations and distribution spaces of each of the hexoses and of the lambda (i.e., ratio of tissue distribution space of DG to that of glucose) of the DG method to the tissue glucose concentration were derived. The lambda was then quantitatively related to the measured equilibrium ratio for [14C]methylglucose over the full range of brain and plasma glucose levels. By combining these new data with the values for the lumped constant, the factor that converts the rate of DG phosphorylation to glucose phosphorylation, previously determined in rats over the same range of plasma glucose levels, the phosphorylation coefficient was calculated and the lumped constant graphed as a function of the measured distribution space in brain for [14C]methylglucose. 相似文献
14.
Single photon emission computed tomography using 99mTc-HM-PAO in the routine evaluation of Alzheimer's disease 总被引:1,自引:0,他引:1
T A Hurwitz W Ammann D Chu C Clark J Holden R Brownstone 《The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques》1991,18(1):59-62
Regional cerebral blood flow was studied in 7 patients with clinically suspected Alzheimer's disease and 10 normal controls by single photon computed emission tomography (SPECT) using HM-PAO. All patients with Alzheimer's disease and no controls had parietal lobe hypoperfusion which was usually bilateral. In patients with more severe dementia hypoperfusion extended into the frontal lobes. Parietal lobe hypoperfusion corresponds to parietal lobe degeneration which is the one of the first neocortical regions to show the typical degenerative changes of Alzheimer's disease. SPECT with HM-PAO is a non-invasive investigation available in most nuclear medicine departments and complements existing tests in the routine evaluation of patients presenting with dementia. 相似文献
15.
Membrane flow within the myelin sheath in IDPN neuropathy 总被引:1,自引:0,他引:1
A. E. BLAUROCK M. B. GENTER ST CLAIR D. G. GRAHAM 《Neuropathology and applied neurobiology》1991,17(4):309-321
This report describes some aspects of beta,beta'-iminodipropionitrile (IDPN) neuropathy in rats as observed by ultrastructural methods and X-ray diffraction. Light microscopy shows gross swelling of the axons in proximal lumbar spinal roots 8 days after intraperitoneal injection of IDPN. Mean axon cross-sectional area and mean axon perimeter increased to 280% and 160% of their control values, respectively. At the same time, myelin membrane packing was not visibly disturbed. In addition, X-ray diffraction patterns, recorded under physiological conditions, demonstrate that the myelin lipid bilayer thickness and widths of the aqueous spaces between bilayers did not change. Related observations are made on posterior tibial nerve (PNS myelin) and ventral spinal cord (CNS myelin). The various observations together are interpreted in terms of a fluid myelin membrane. It is proposed that the myelin membrane flows during axon swelling even though normal membrane-membrane contacts are maintained within the sheath. Membrane flow and slippage between membranes are explained in terms of a molecular model of the myelin multilayer. 相似文献
16.
M D Holden 《Postgraduate medicine》1992,91(8):191-4, 199-200
17.
18.
The literature addressing the mental health of homeless children is critically reviewed. Higher rates of behavioral, emotional, and cognitive problems have been reported for this population, but research results are qualified by significant methodological problems. Minimal attention has been given to the development and evaluation of specific intervention and prevention strategies. Recommendations are made for conducting research that will overcome previous methodological problems and focus more directly on identifying risk and protective mechanisms within the population of children exposed to homelessness. 相似文献
19.
N. J. ST. G. SAUNDERS Lecturer C. BARCLAY Registrar 《BJOG : an international journal of obstetrics and gynaecology》1988,95(10):1060-1062
Summary. In a randomized controlled study of wound suction drainage after transverse suprapubic incision for lower-segment caesarean section no significant advantages could be demonstrated for routine drainage in terms of wound infection, haematoma formation, duration of hospital stay or analgesic requirements. 相似文献
20.
As part of a study examining the effects of contact lens extended wear in monkeys (Macaca fascicularis), reversible endothelial changes were observed in the cornea with slit lamp biomicroscopy and contact specular microscopy. These changes were associated with anterior eye inflammation in four monkeys (as occurs in humans). However, in two monkeys no obvious cause for these changes other than the presence of a contact lens on the cornea was apparent. In these two monkeys the endothelium displayed features similar to the transient endothelial bleb response, which has been observed only in humans. The monkey (M fascicularis) may thus be an appropriate model for further investigation of the endothelial response during anterior eye inflammation and the transient endothelial bleb response. 相似文献