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21.
We have developed a general quenched-flow approach to study platelet function as early as 0.3 seconds after stimulation. Phosphorylation of 20- and 40-kd proteins has been analyzed during the first five seconds of platelet response to thrombin from 0.1 to 5.0 U/mL and compared with the progress of aggregation and serotonin secretion. The onset time for aggregation and phosphorylation of both proteins was less than one second, although with lowest (less than 0.5 U/mL) thrombin levels, a lag of up to 0.6 seconds occurred before 40K phosphorylation increased. The thrombin sensitivity of aggregation and 20K phosphorylation was approximately twice that of 40K phosphorylation, with Ka values of 0.51 and 0.53 v 1.10 U/mL, respectively. External calcium was necessary for maximal 20K phosphorylation, since EDTA inhibited this by 30%. The 40K phosphorylation was not affected by EDTA. Platelet activation by thrombin thus induced biochemical changes well before one second. The quenched-flow approach may help to reveal relationships between phospholipase activation, calcium fluxes, and protein phosphorylation during these early periods of platelet function. 相似文献
22.
Diagnostic role of an immunoassay-detected polymorphism of factor IX for potential carriers of hemophilia B 总被引:3,自引:1,他引:3
In hemophilia B, assays based on a monoclonal antifactor IX specific for the Thr-148 variant of an exonic polymorphism have diagnosed carriers in selected families by either establishing linkage or by indicating the presence or absence of a given normal factor IX. The sensitivity of the immunoassays for detecting heterozygous women was explored by comparing results from immunoassays with solid-phase polyclonal v the monoclonal antifactor IXs. Factor IX with the normal Ala-148 variant gave a flat dilution curve, qualitatively distinct from factor IX with the Thr-148 variant in the monoclonal assay. The two were indistinguishable in the polyclonal assay. Mixtures of equal amounts of the two types gave an intermediate result, about half as reactive in the monoclonal as compared with the polyclonal assay system. Whereas mixtures with 10% Ala-148 and 90% Thr-148 factor IXs could not readily be distinguished from Thr-148 factor IX plasma, as little as 1% of the Thr-148 protein was detected in Ala-148 factor IX plasma. The frequency of the Ala-148 variant varied in individuals with different ethnic backgrounds; it was found in 29% of white, 12% of black, and none of Asian blood donors' factor IX genes in Seattle. Only 4% of samples from South African black men were nonreactive (ie, Ala- 148). The Thr/Ala-148 dimorphism is in strong linkage disequilibrium with Taql restriction fragment length polymorphisms (RFLPs). Three recombinations were noted in normal white genes and one in a normal black factor IX gene (less than 2% of those examined). In 34 white families with at least one woman being a possible carrier, genetically, the immunoassay results were informative in 18. RFLP analyses were informative in eight of the 15 families tested. In five families each, assignment of carrier status was made to a woman by only DNA or only immunoassay results, whereas the other approach was noninformative. The immunoassays provide a rapid, inexpensive screening test and complement DNA analysis in white women who are potential carriers of hemophilia B. 相似文献
23.
SMJ Mortazavi MA Mosleh-Shirazi AR Tavassoli M Taheri AR Mehdizadeh SAS Namazi A Jamali R Ghalandari S Bonyadi M Haghani M Shafie 《Dose-response》2013,11(2):281-292
The aim of this study was to investigate the effect of pre-irradiation with microwaves on the induction of radioadaptive response. In the 1st phase of the study, 110 male mice were divided into 8 groups. The animals in these groups were exposed/sham-exposed to microwave, low dose rate gamma or both for 5 days. On day six, the animals were exposed to a lethal dose (LD). In the 2nd phase, 30 male rats were divided into 2 groups of 15 animals. The 1st group received microwave exposure. The 2nd group (controls) received the same LD but there was no treatment before the LD. On day 5, all animals were whole-body irradiated with the LD. Statistically significant differences between the survival rate of the mice only exposed to lethal dose of gamma radiation before irradiation with a lethal dose of gamma radiation with those of the animals pre-exposed to either microwave (p=0.02), low dose rate gamma (p=0.001) or both of these physical adapting doses (p=0.003) were observed. Likewise, a statistically significant difference between survival rates of the rats in control and test groups was observed. Altogether, these experiments showed that exposure to microwave radiation may induce a significant survival adaptive response. 相似文献
24.
Benzo[a]pyrene at an environmentally relevant dose is slowly absorbed by, and extensively metabolized in, tracheal epithelium 总被引:2,自引:0,他引:2
Gerde P; Muggenburg BA; Thornton-Manning JR; Lewis JL; Pyon KH; Dahl AR 《Carcinogenesis》1997,18(9):1825-1832
While tobacco smoke has been conclusively identified as a lung carcinogen,
there is much debate over which smoke constituent(s) are primarily
responsible for its carcinogenicity. Previous studies in our laboratory
suggested that highly lipophilic carcinogens are slowly absorbed in the
thicker epithelium of the conducting airways, potentially allowing for
substantial local metabolism. The bioactivation of polycyclic aromatic
hydrocarbons in airway epithelium may, hence, be important in tobacco
smoke-induced carcinogenesis. In the present study, the hypothesis of slow
absorption and substantial local metabolic activation of highly lipophilic
carcinogen in airway epithelium was tested in dogs. A single dose of
tritiated benzo[a]pyrene (BaP) dissolved in a saline/phospholipid
suspension was instilled in the trachea, just anterior to the carina. At
intervals of a few minutes up to 30 min over a 3-h period, blood samples
were drawn from the azygous vein, which drains the area around the point of
instillation, and from the systemic circulation. Tissue samples were taken
at the end of the experiment. The concentration of BaP with depth into the
tracheal mucosa was determined with autoradiography. BaP was slowly
absorbed into the trachea with a half-time of approximately 73 min, which
is consistent with diffusion-limited passage through the epithelium and
lead to local doses in the tracheal epithelium that were more than a
1000-fold those of other tissues. The long retention of BaP in the
epithelium provided the local metabolizing enzymes with high substrate
levels over a long period, resulting in extensive metabolism. At 3 h after
the exposure, 23% of the BaP-equivalent activity remained in the tracheal
mucosa. Of this fraction, 13% was parent compound, 28% was organic
extractable, 31% was water-soluble, and 28-7% of the instilled dose was
bound to tracheal tissues. These results explain the tendency of highly
lipophilic carcinogens, such as BaP, to induce tumors at the site of entry
and, furthermore, indicate that the highly lipophilic components of tobacco
smoke and polluted air may be the most important contributors to lung
tumors of the conducting airways.
相似文献
25.
MT Bardella N Molteni L Prampolini AM Giunta AR Baldassarri D Morganti PA Bianchi 《Archives of disease in childhood》1994,70(3):211-213
The use of follow up studies was evaluated in 128 patients with coeliac disease during their first visit to a department for adults. The original diagnosis had been made in childhood in all patients. Fifty eight (45%) of the subjects were following a gluten free diet, 23 (18%) were following a gluten free diet but with occasional gluten consumption, and 47 (37%) had adopted an unrestricted, gluten containing diet for a mean of 11.2 years. There was no correlation in individual subjects between the presence of symptoms, biochemical and immunological abnormalities, severity of histological findings, and the amount of dietary gluten, despite the greater frequency of symptoms in the group following an unrestricted diet than in the other two groups. Short stature and epilepsy with cerebral calcifications only occurred in patients following an unrestricted diet. As only diagnosis based on two or three biopsy samples and regular follow up correlated positively with dietary compliance, it is suggested that a histologically confirmed diagnosis of coeliac disease and regular lifelong follow up are essential in the management of these patients. 相似文献
26.
STOTT DJ; MCLELLAN AR; FINLAYSON J; CHU P; ALEXANDER WD 《QJM : monthly journal of the Association of Physicians》1991,78(1):77-84
The clinical and biochemical characteristics of 15 elderly patientswith low levels of thyrotrophin (TSH) (<0.1 mU/L) but normalfree tri-iodothyronine, (T3) and free thyroxine (T4) (groupS) were compared with 10 euthyroid subjects (group E) and 10hyperthyroid patients (group T). Free T3 and free T4 were significantlyhigher (p<0.05) in group S(6.3±0.5 and 18.6±1.0pmol/l, respectively) than in group E(4.6±0.3, 12.6+0.6).In common with elderly hyperthyroid patients (group T)patientsin group S had few signs or symptoms of thyrotoxocosis, butthe Wayne score (clinical index of hyperthyroidism) was higherin group S than in euthyroid subjects (p<0.05). Thyroid microsomal,thyrogolobulin or thyrotrophin receptor antibodies were commonin group T (n=9)but not in groups S(n=2) or E(n=1). This suggestsa low prevalence of Graves' disease in group S compared to groupT. Combined thyrotrophin releasing hormone (TRH; 200 µgi.v.) and gonadotrophin releasing hormone GnRH; 100 µgi.v.) tests were performed; no cases of low TSH due to hypopituitarismwere identified in group S. During a mean of 7.9 (412)months of observation TSH reverted to the normal range (>0.2mU/L)in 7 of 15 patients in group S; thyroid hormone concentrationsrose above the normal range in four, however, only two patientsrequired treatment for hyperthyroidism. It is unlikely thatthe suppressed TSH of patients in group S was due to mild thyroidhormone excess; although this is often a transitory phenomenon,these patients are at increased risk of developing overt hyperthyroidism. 相似文献
27.
28.
WVBS Ramalingam D Chikara G Rajagopal AVSM Prof AR Mehta S Sarkar 《Medical Journal Armed Forces India》2007
Background: Stage III and IV cancers of larynx and hypopharynx often require total laryngectomy which leaves the patient with severe communication handicap. In such laryngectomised patients tracheo-esophageal puncture is the best way for voice rehabilitation using either Blom-Singer® prosthesis or Provox® indwelling valve. 相似文献
29.
AR Genazzani G Sandrini F Facchinetti V Rizzo E Alfonsi G Sances M Calvani G Nappi 《Cephalalgia : an international journal of headache》1986,6(4):241-245
L-Tryptophan (L-TP) has been used in migraine and other pain conditions. The mechanism underlying the analgesic effect is still partly undefined. In this study the effects of subchronic administration of L-5-hydroxy-tryptophan (L-5HTP) (with and without carbidopa) on plasma beta-endorphin (beta-EP) levels and subjective pain threshold and tolerance were investigated in seven healthy volunteers. To measure also an objective indicator for pain, the nociceptive flexion reflex threshold was studied. L-5HTP treatment with and without carbidopa administration increased beta-EP levels significantly (p less than 0.05). L-5HTP plus carbidopa induced an increase in beta-EP significantly (p less than 0.05) higher than that after L-5HTP alone. Neither subjective pain threshold and tolerance nor RIII threshold was modified by either treatment. Our data seem to point to the existence of a complex linkage between plasma opioid levels and pain perception. 相似文献
30.
Peptic ulcer and gastric carcinoma: diagnosis with biphasic radiography compared with fiberoptic endoscopy 总被引:1,自引:0,他引:1
Shaw PC; van Romunde LK; Griffioen G; Janssens AR; Kreuning J; Eilers GA 《Radiology》1987,163(1):39-42
The diagnostic value of biphasic radiographic examination of the stomach and duodenum was compared with that of fiberoptic endoscopy in a prospective, blinded study of 385 patients with dyspepsia. This investigation was directed at gastric malignancies and peptic ulcers. Methodologically there is no absolute standard for a study of this kind because histologic examination is useful for detection of cancer but inadequate for ulcers. As an alternative, kappa indexes and the sensitivity and specificity, as derived by Hui and Walter, were calculated and compared. For the detection of gastric carcinoma, radiographic and endoscopic findings had almost perfect agreement beyond chance. For gastric ulcers, radiography and endoscopy had substantial agreement, which became perfect if small ulcers (less than 5 mm) were excluded. For duodenal ulcers, radiography had a lower sensitivity than endoscopy; this disagreement disappeared if small ulcers were excluded. Both methods have equal merit; choice of the initial diagnostic procedure will therefore depend on cost, discomfort to the patient, and risk of complications. 相似文献