Influence of sinus impulses on the parasystolic cycle length

Recently, it has been shown that in most clinical cases of parasystole, the parasystolic rhythm is not completely independent of the sinus rhythm. In this study, to disclose the mechanism of such "irregular" parasystole, parasystolic cycles with an intervening sinus QRS complex (XSX) were compared with their immediately adjacent pure parasystolic cycles without any intervening nonparasystolic QRS complexes (XX) in 10 cases of ventricular parasystole. In eight cases, the XSX interval was equal to or nearly equal to the adjacent pure XX interval; in one, the XSX interval was shorter than the XX interval; and in only one, the XSX interval was longer than the XX interval. In six cases in which the XSX interval was almost equal to the XX interval, calculated XSX intervals with a later intervening sinus QRS complex were obtained from the differences between the XSSX interval (ie, interectopic interval with two intervening sinus QRS complexes) and its adjacent XX interval. In five of the six cases, the calculated XSX interval was shorter than the XX interval. These observations suggest that in most cases of parasystole, early intervening sinus impulses do not change the parasystolic cycle, whereas late intervening sinus impulses shorten the parasystolic cycle. This suggests the presence of type I second-degree entrance block as the mechanism of "irregular" parasystole.     

Effects of estrus cycle on thermoregulatory responses during exercise in rats

Summary In female rats, rectal temperature (T _re), tail vasomotor response, oxygen uptake , and carbon dioxide production were measured in proestrus and estrus stages during treadmill running at two different speeds at an ambient temperature (T _a) of 24° C. Experiments were performed at 2.00–6.00 a.m., when the difference inT _re was greatest between the two stages;T _re at rest in the estrus stage was 0.54° C higher than in the proestrus stage. In a mild warm environment, thresholdT _re for a rise in tail skin temperature (T _tail) was also higher in the estrus stage than in the proestrus stage. In contrast, no difference was seen in the thresholdT _re and steady stateT _re at the end of exercise between proestrus and estrus stages. These values were higher at the higher work intensity. was also similar between the two stages, except in the second 5 min after the beginning of exercise, when was greater andT _re rose more steeply in the proestrus stage. These data indicate that deep body temperature during exercise is regulated at a certain level depending on the work intensity and is not influenced by the estrus cycle.This study was supported in part by a Grant-in Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan (Grant No. 62480114)     

Effects of arousal and natural baroreceptor activation on the human muscle stretch reflex

The nociceptive flexion reflex is inhibited during systole; this inhibition may be due to increased baroreceptor stimulation. It is yet to be determined whether other spinal reflexes are similarly modulated across the cardiac cycle. There is also evidence that stretch and tendon reflexes are facilitated by increased arousal. This study investigated the effects of phase of the cardiac cycle and arousal on the muscle stretch reflex components M1, M2, and M3. Stretch reflexes were elicited in leg muscles at six intervals across the cardiac cycle during rest, number repetition, and mental arithmetic. Mental arithmetic provoked increased cardiovascular arousal and facilitated both M1 and M2 compared to rest and number repetition. The stretch reflex did not vary with the phase of the cardiac cycle. While the stretch reflex is susceptible to arousal, natural baroreceptor-mediated modulation across the cardiac cycle may be specific to nociception.     

Identification of 16 novel mutations in the argininosuccinate synthetase gene and genotype-phenotype correlation in 38 classical citrullinemia patients

Classical citrullinemia (CTLN1), a rare autosomal recessive disorder, is caused by mutations of the argininosuccinate synthetase (ASS) gene, localized on chromosome 9q34.1. ASS functions as a rate-limiting enzyme in the urea cycle. Previously, we identified 32 mutations in the ASS gene of CTLN1 patients mainly in Japan and the United States, and to date 34 different mutations have been described in 50 families worldwide. In the present study, we report ASS mutations detected in 35 additional CTLN1 families from 11 countries. By analyzing the entire coding sequence and the intron-exon boundaries of the ASS gene using RT-PCR and/or genomic DNA-PCR, we have identified 16 novel mutations (two different 1-bp deletions, a 67-bp insertion, and 13 missense) and have detected 12 known mutations. Altogether, 50 different mutations (seven deletion, three splice site, one duplication, two nonsense, and 37 missense) in 85 CTLN1 families were identified. On the basis of primary sequence comparisons with the crystal structure of E. coli ASS protein, it may be concluded that any of the 37 missense mutations found at 30 different positions led to structural and functional impairments of the human ASS protein. It has been found that three mutations are particularly frequent: IVS6-2A>G in 23 families (Japan: 20 and Korea: three), G390R in 18 families (Turkey: six, U.S.: five, Spain: three, Israel: one, Austria: one, Canada: one, and Bolivia: one), and R304W in 10 families (Japan: nine and Turkey: one). Most mutations of the ASS gene are "private" and are distributed throughout the gene, except for exons 5 and 12-14. It seems that the clinical course of the patients with truncated mutations or the G390R mutation is early-onset/severe. The phenotype of the patients with certain missense mutations (G362V or W179R) is more late-onset/mild. Eight patients with R86H, A118T, R265H, or K310R mutations were adult/late-onset and four of them showed severe symptoms during pregnancy or postpartum. However, it is still difficult to prove the genotype-phenotype correlation, because many patients were compound heterozygotes (with two different mutations), lived in different environments at the time of diagnosis, and/or had several treatment regimes or various knowledge of the disease.     

Contraction-specific differences in maximal muscle power during stretch-shortening cycle movements in elderly males and females

Elderly people (age 75 years; n=48 males and 34 females) were studied in order to elucidate gender differences in elderly subjects on the determinants of muscle power (force and velocity) during a stretch-shortening cycle. All subjects performed three maximal counter-movement vertical jumps using both legs, on a force platform (Kistler 9281 B). The eccentric (Ep) and concentric (Cp) phases of the jumps were analyzed. The Ep was further divided into an acceleration phase (Ep_acc: from the start of the downward movement to the maximal negative velocity) and deceleration phase (Ep_dec: from the maximal negative velocity to the end of the downward movement). Jump height for the men was higher than for the women (P < 0.001). During both Ep_acc and Ep_dec no significant differences were observed between males and females in force and power generation. However, the men had a higher peak muscle power during the Cp, which may be explained exclusively by the velocity determinant (P < 0.001). No specific gender-related strategy appeared to influence the motor pattern of the movement. The comparable eccentric force generation of the leg extensors in both genders suggests a similar ability to cope with eccentric muscle actions during everyday activities. In contrast, the marked lower capacity for concentric contractions in women may result in an impaired performance, especially in activities where intense and rapid movements are essential, for example when reversing a forward fall. This may be one reason why elderly women are more prone to falls than are elderly men. Accepted: 19 September 2000     

Deregulation of the G1/S-phase control in human testicular germ cell tumours

Deregulated cell cycle and defective genome-integrity checkpoints are among the hallmarks of cancer.Here we summarize our recent studies of key components of the GI/S machinery in normal human spermatogenesis, and their abnormalities in testicular germ cell tumours (TGCTs), with special emphasis on carcinoma in situ lesions (CIS). Our combined immunohistochemical and immunoblotting analyses of normal human adult and fetal testes, CIS, seminomas, embryonal carcinomas, and teratomas, revealed an 'unorthodox' spectrum of defects within the so-called RB pathway in TGCTs. The early aberrations included lack of expression of the retinoblastoma tumour suppressor (pRB) and the CDK inhibitor pl9ink4d, and overexpression of cyclin D2. Progression from CIS to invasive TGCTswas associated with loss of another two CDK inhibitors and tumour suppressors: pl6ink4a and pl8ink4c. We also found the lack of pRB and pl9ink4d in fetal gonocytes, the candidate target cell for all types of TGCTs. These findings, together with the status of the Chk2-p53 DNA-integrity checkpoint, are considered in relation to the origin, biology and pathogenesis of TGCTs, and potential implications of the GI/S defects for the curability of these tumours.     

聚维酮联合阿霉素体外抑制膀胱癌细胞T24生长并预防膀胱癌患者术后复发

目的探讨聚维酮(PVP)联合阿霉素(ADM)对人膀胱癌细胞株T24的作用及预防膀胱癌术后复发的疗效。方法MTT法检测细胞生长抑制率,流式细胞仪检测细胞周期和黏附作用。对231例浅表膀胱癌患者术后膀胱灌注PVP ADM(实验组)或生理盐水 ADM(对照组),观察预防复发效果。结果2·5%PVP作用24h和72h细胞生长抑制率为15·11%和49·57%;7·5%浓度时,抑制率升为35·42%和79·66%。单用0·25mg/LADM作用48h抑制率为39·05%;合用2·5%和7·5%PVP抑制率升为68·51%和88·39%。5%PVP能使T24细胞的G0/G1期比率下降和G2/M期比率上升。PVP能提高抗鼠IgG1对T24细胞的黏附作用。194例患者获随访,实验组复发率明显降低,复发时间明显延长(均P<0·01)。结论PVP通过阻滞细胞周期G2/M期和增强黏附作用来抑制T24细胞生长,与ADM联合具有协同作用。PVP联合ADM膀胱灌注预防浅表膀胱癌术后复发疗效确切,副作用少。     

Development of flow cytogenetics and physical genome mapping in chickpea (Cicer arietinum L.)

Procedures for flow cytometric analysis and sorting of mitotic chromosomes (flow cytogenetics) have been developed for chickpea (Cicer arietinum). Suspensions of intact chromosomes were prepared from root tips treated to achieve a high degree of metaphase synchrony. The optimal protocol consisted of a treatment of roots with 2mmol/L hydroxyurea for 18h, a 4.5-h recovery in hydroxyurea-free medium, 2h incubation with 10µmol/L oryzalin, and ice-water treatment overnight. This procedure resulted in an average metaphase index of 47%. Synchronized root tips were fixed in 2% formaldehyde for 20min, and chromosome suspensions prepared by mechanical homogenization of fixed root tips. More than 4×10⁵ morphologically intact chromosomes could be isolated from 15 root tips. Flow cytometric analysis of DAPI-stained chromosomes resulted in histograms of relative fluorescence intensity (flow karyotypes) containing eight peaks, representing individual chromosomes and/or groups of chromosomes with a similar relative DNA content. Five peaks could be assigned to individual chromosomes (A, B, C, G, H). The purity of sorted chromosome fractions was high, and chromosomes B and H could be sorted with 100% purity. PCR on flow-sorted chromosome fractions with primers for sequence-tagged microsatellite site (STMS) markers permitted assignment of the genetic linkage group LG8 to the smallest chickpea chromosome H. This study extends the number of legume species for which flow cytogenetics is available, and demonstrates the potential of flow cytogenetics for genome mapping in chickpea.