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81.
Human myeloma light chains with increased molecular weight: high frequency among lambda chains 总被引:2,自引:0,他引:2
The discovery of a human myeloma protein comprising a kappa L-chain with an increased mol. wt of 30,000) (Bouvet et. al., 1980) prompted investigations on the incidence of such heavier L-chains among other human myeloma proteins. In 105 samples examined, 34 were found to have L-chains heavier than normal (23,000-24,000), ranging from 25,000 up to 31,000, and five of lighter mol. wt (21,000-22,000). These mol. wt abnormalities were detected by electrophoresis in sodium dodecyl sulfate 10% polyacrylamide gels (SDS-PAGE) after reduction with 2-mercaptoethanol. The mol. wt of three of the heavier kappa or lambda chains was also estimated by filtration through a Sephadex G100 column and by sedimentation equilibrium. All three methods indicated a mol. wt increase of about 15-25% as compared with the usual mol. wt. The distribution of the high mol. wt chains among all L-chains examined was found to be 11 out of 62 kappa chains (17.7%) and 23 out of 43 lambda chains (53%) (P less than 0.001). A preferential association of such L-chains with H-chains producing multiple bands in SDS-PAGE (P less than 0.01) and an association between multiple L-chain and multiple H-chain band (P less than 0.05) were also observed. In contrast, no abnormal L-chain was found in immunoglobulins from normal subjects. Spontaneous degradation of the normal H-chains sometimes yielded fragments of 30,000 mol. wt. These fragments were easily distinguishable from abnormal L-chains. The nature of extra mol. wt in heavy L-chains was investigated for the presence of carbohydrate moiety. Four large and three normal size L-chains were examined for amino-sugar and sialic acid content. A small amount (one residue per molecule) of amino-sugar was detected only in two normal and two heavy L-chains, whereas sialic acid was only found in the heaviest (27,000-30,000) L-chains (Lh) and in small percentage (one or two residues per molecule). Total sugar estimation in one Lh chain indicated a proportion not exceeding three or four residues per L-chain (mol. wt 1,000) and this is insufficient to explain the 15-25% (3,600-6,000) mol. wt increase. It is therefore possible that, at least in some heavy myeloma L-chains, an additional peptide is expressed. Whatever the nature of the increase it would be of interest to elucidate whether this is a marker of malignant process or of an intermediate step of normal Ig synthesis. 相似文献
82.
George B. Haycock 《Pediatric nephrology (Berlin, Germany)》1993,7(6):871-875
Sodium (Na) is an important growth factor, stimulating cell proliferation and protein synthesis and increasing cell mass. Sodium chloride (NaCl) deprivation inhibits growth, as reflected by reduced body and brain weight, length, muscle and brain protein and RNA content and brain lipid content compared with controls. This is not due to deficiency of other nutrients since control and experimental diets were identical except for NaCl content. Subsequent NaCl supplementation restores growth velocity to control values but does not induce catch-up growth. In humans, salt loss causes growth failure and subsequent salt repletion improves growth. Preterm infants <32 weeks' gestation at birth are renal salt losers in the first 2 weeks of post-natal life and are vulnerable to hyponatraemia. This can be prevented by increasing Na intake, which also produces accelerated weight gain that persists beyond the period of supplementation. Early nutrition in preterm infants can affect subsequent growth and also cognitive function: this is probably multifactorial, but NaCl intake differed substantially between study groups and is likely to be an important factor. The mechanism whereby Na promotes cell growth is not understood, but stimulation of the membrane Na+,H+-antiporter with alkalinization of the cell interior is a likely possibility. 相似文献
83.
Kurata M 《Journal of anesthesia》1993,7(3):325-333
31P and 23Na nuclear magnetic resonance (NMR) spectroscopy was employed to study the dynamic changes in intracellular high-energy phosphates and sodium during 15min of forebrain ischemia and recirculation in in vivo rat brain. In the presence of the shift reagent Dysprosium triethylenetetramine-N,N,N,N,N,N-hexaacetic and [Dy(TTHA)], the sodium peak separated into two peaks, unshifted and shifted. During 15min of ischemia, the unshifted sodium peak decreased and the shifted sodium peak increased. With recirculation, the unshifted and the shifted sodium peaks returned to the preischemia level within 10min, but the shifted one increased during 30–60min. Intracellular high-energy phosphates and intracellular pH (pHi) decreased during 15min of ischemia and returned to the preischemia levels within 20min of recirculation. We conclude that the decrease in unshifted sodium peak during ischemia is due to the decrease in subarachnoid sodium and the cellular influx of interstitial sodium would be minimum. The increase in shifted sodium peak during ischemia is considered to be due to the dilatation of cerebral blood vessels and the increase in interstitial sodium which was transported from subarachnoid space.(Kurata M: 31P and 23Na nuclear magnetic resonance study on forebrain ischemia in rats with shift reagent Dy(TTHA). J Anesth 7: 325–333, 1993) 相似文献
84.
F. Terzi B. M. Assael A. Claris-Appiani G. Marra C. A. Dell'Agnola B. Tadini V. Tomaselli 《Pediatric nephrology (Berlin, Germany)》1990,4(6):581-584
Serum electrolyte equilibrium and plasma aldosterone concentrations were monitored in 19 infants who had severe obstructive uropathy or grade 5 vesico-ureteral reflux and were undergoing surgical correction in the first 2 months of life. Before surgery high plasma aldosterone levels were observed in 8 patients, but serum sodium and potassium concentrations were normal. Plasma concentrations of aldosterone were elevated in all patients during the week following surgery and 7 patients developed severe hyponatraemia, hyperkalaemia and weight loss despite very high plasma aldosterone concentrations. As a consequence 5 infants were infused with sodium chloride (4 mEq/kg per day) before and for 36h after surgery; this prevented metabolic imbalance. We conclude that infants undergoing surgical correction of uropathies may require a high sodium intake to maintain electrolyte balance and adequate growth. 相似文献
85.
目的 评价四种不同方法治疗血管瘤远期疗效。方法 取 1992~ 1998年共七年间我院门诊及住院分别患有毛细血管瘤、海绵状血管瘤、蔓状血管瘤病人 2 33例 ,分别采取血管瘤营养血管结扎 平阳霉素注射、5 %鱼肝油酸钠注射、平阳霉素 强的松龙注射、平阳霉素 5 %鱼肝油酸钠注射 4种治疗方法 ,并对上述 4种方法血管瘤注射后进行随访及疗效评定。结果 血管瘤营养血管结扎 平阳霉素注射组总有效率及显效率均较其余 3组高 ,而单纯应用鱼肝油酸钠血管瘤注射组较其余 3组无论是总有效率或显效率均低。结论 联合用药较单一用药治疗血管瘤效果好 ,而血管瘤远期疗效与药物在瘤体内存留时间长短有关 ,停留时间愈长 ,其有效率愈高 ,而缝扎血管瘤营养血管后无疑为药物在血管瘤内长时间停留提供条件。 相似文献
86.
L. Erlacher H. Teufelsbauer P. Bernecker P. Pietschmann M. Weissel 《Journal of molecular medicine (Berlin, Germany)》1994,72(12):1082-1085
Fluoride salts are widely used in Europe in the treatment of established osteoporosis with crush fractures for their ability to increase trabecular bone mass. However, in the United States fluorides are still regarded as an experimental drug. In a prospective, randomized study we compared the fluoride pharmacokinetics of enteric-coated sodium fluoride and disodium monofluorophosphate calcium carbonate (MFP-Ca) over the period of 76 h. Twenty subjects (12 females, 8 males), aged 35–80 years, free of gastrointestinal disorders, renal impairment, and liver disease and without prior fluoride intake entered the study. Ten subjects received NaF (11.3 mg fluoride) twice a day and the other ten MFP-Ca (13.2 mg fluoride) twice a day. During the study period of 76 h the patient's usual food intake was not changed. Serum fluoride levels were determined using an ion sensitive electrode. After intake of a single drug preparation of MFPCa or NaF, MFP-Ca showed a significantly shorter lag time of absorption and a significantly higher maximal serum fluoride concentration than NaF (P<0.01). A comparison of fluoride cumulative characteristics of both drugs showed virtually identical serum fluoride levels before intake of the morning dose on all 4 study days, whereas serum fluoride concentrations measured 4 h afterwards were significantly higher for MFP-Ca than for NaF. These data provide evidence of high peak serum fluoride levels for MFP-Ca, whereas only small peak-to-trough fluctuations are seen for NaF.Abbreviations MFP-Ca
disodium monofluorophosphate-calcium carbonate
-
C
max
maximum drug concentration
-
T
max
lag time of maximum drug concentration
- AUC
area under the serum concentration versus time curve
Correspondence to: L. Erlacher 相似文献
87.
Tomoaki Yuhi Akihiko Wada Ryuichi Yamamoto Masanobu Urabe Hiromi Niina Futoshi Izumi Toshihiko Yanagital 《Naunyn-Schmiedeberg's archives of pharmacology》1994,350(2):209-212
We have previously reported that in bovine adrenal chromaffin cells Ptychodiscus brevis toxin-3 (PbTx-3) does not alter the veratridine-induced 22Na influx when given alone, but increases the influx of 22Na when co-applied with either - or -scorpion venom (Wada et al. 1992). In the present study, we characterized [3H]PbTx-3 binding in bovine adrenal chromaffin cells. [3H]PbTx-3 binding was saturable, reversible and of high-affinity with an equilibrium dissociation constant (Kd) of 32.0±4.9 nmol/1 and a maximum binding capacity Bmax of 6.2 ± 1.2 pmol/4 × 106 cells (4.5 ± 0.9 pmol/mg cell protein). A Hill plot revealed the lack of cooperative interaction among the binding sites. Unlabelled PbTx-3 inhibited [3H]PbTx-3 binding with an IC50 of 31 nmol/l. However, tetrodotoxin, veratridine, - and -scorpion venom, or veratridine in combination with either - or -scorpion venom did not alter [3H]PbTx-3 binding. All these results suggest that PbTx-3 binds to a site (site 5) distinct from the previously known four toxin binding sites, which does not gate voltage-dependent Na channels by itself, but is specifically involved in the allosteric modulation of Na channels in adrenal medullary cells.
Correspondence to: A. Wada at the above address 相似文献
88.
89.
A. De Luca F. Natuzzi G. Lentini C. Franchini V. Tortorella D. Conte Camerino 《Naunyn-Schmiedeberg's archives of pharmacology》1995,352(6):653-661
The effects of the enantiomers of mexiletine were tested on sodium currents of frog skeletal muscle fibers recorded by means of the three vaseline gap voltage clamp method and compared with the effects produced by tocainide enantiomers. The R-( – ) mexiletine produced a tonic block of the sodium current, elicited by single depolarizing test pulses from the holding potential of – 100 mV to – 20 mV, with an IC50 of 43.9 ± 1 M, whereas the corresponding S-( + ) enantiomer produced the same effects at about twofold higher concentrations. A similar stereoselectivity was observed with tocainide enantiomers, but at about 5 fold higher concentrations. Both the R-( – ) and S-( + ) enantiomers of mexiletine and tocainide produced a further use-dependent block of sodium currents when the test pulse was applied repetitively at a frequency of 2 Hz. The use dependent behaviour led to a significant lowering of the IC50 values with respect to the tonic block but the eudismic ratios ([IC50S-( + )]/[IC50R( – )]) and the relative potency between mexiletine and tocainide were maintained. All the tested compounds produced a left shift of the steady state inactivation curves (h) , suggesting a high-affinity interaction with the inactivated sodium channels. Again a stronger potency of R-( – ) vs. S-( + ) enantiomers and of mexiletine vs. tocainide was observed. The excitability characteristics recorded from the semitendinosus muscle by the two microelectrode technique were modified by the tested drugs in agreement with their ability to block sodium current. Thus a concentration-related increase in the threshold current required to elicit an action potential was observed along with a decrease in the amplitude and a shortening of the latency of action potential and a decrease in the firing capability of the membrane. Again the R-( – ) isomers were more potent than the S-( + ) ones and mexiletine was more effective than tocainide. These data corroborate the presence of a stereospecific site for these drugs on adult skeletal muscle sodium channels. The constant eudismic ratios between the enantiomers during both tonic and use-dependent block suggest that the increase in the apparent affinity of the receptor during statedependent conformational changes of the channel does not enhance its stereospecificity. The decrease in effective concentration upon high frequency stimulation supports the potential usefulness of low doses of R-( – ) mexiletine in the treatment of the abnormal hyperexcitability of the myotonic muscles, with a likely reduction of unwanted side effects. 相似文献
90.
Electrophysiological effects of dridocainide on isolated canine,guinea-pig and human cardiac tissues
C. Pankucsi P. P. Nánási M. Hegedüs A. Kovács G. Szénási K. Szemerédi 《Naunyn-Schmiedeberg's archives of pharmacology》1995,352(5):520-528
The cellular electrophysiological effects of dridocainide (EGIS-3966), a novel class I antiarrhythmic agent, was studied using conventional microelectrode techniques in canine cardiac Purkinje fibres and papillary muscle preparations obtained from humans and guinea-pigs. In each preparation, dridocainide (0.6–2 mol/l) decreased the maximum velocity of action potential upstroke (Vmax) in a frequency-dependent manner, although marked differences were observed in its effects in Purkinje fibre and ventricular muscle preparations. In canine Purkinje fibres, action potential duration measured at 50% and 90% of repolarization was decreased, while action potential duration measured at 10% of repolarization was increased by dridocainide. In addition, the plateau of the action potential was depressed by the drug. These changes in action potential configuration were not observed in guinea pig or human papillary muscles. The offset kinetics of the dridocainide-induced V
max block were different in Purkinje fibres and in ventricular muscle: the slow time constant of recovery of V
max was estimated to be 2.5 s in dog Purkinje fibre and 5–6 s in human and guinea-pig papillary muscle. In guinea-pig papillary muscle, the rate of onset of the V
max block was 0.15 and 0.2 per action potential in the presence of 0.6 and 2 mol/l dridocainide, respectively. Dridocainide also decreased the force of contraction in this preparation. On the basis of the present results, dridocainide appears to posess mixed class LC and LA properties, with LC predominance in human and guinea-pig ventricular muscle. Present results also indicate that results of conventional classification of class I drugs may depend on the parameters chosen, as well as on the preparation selected. 相似文献