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61.
Among other characteristics, the steady-state current-voltage relationship of patch-clamped single atrial myocytes from guinea-pig hearts is defined by an outward current hump in the potential region –15 to +40mV. This hump was reversibly suppressed by Co2+ (3 mM) or nitrendipine (5 M) and enhanced by Bay K 8644 (5 M). The maintained outward current component suppressed by Co2+ extended between –15.2±1.9 mV and +39.5 ±1.7 mV (mean±SEM of 14 cells) and has an amplitude of 95.7±9.4 pA at +10 mV. In isochronal I-V curves, the hump was already visible at 400 ms with essentially the same amplitude as at 1500 ms. The Co2+ -sensitive outward current underlying the hump was poorly time-dependent during 1.5 s voltage pulses but slowly relaxed upon repolarization. Tail currents reversed near the K+ equilibrium potential under our experimental conditions. The current hump of the steady-state I-V curve was also abolished by caffeine (10 mM) or ryanodine (3 M), both drugs that interfere with sarcoplasmic reticulum function. Apamin (1 M) or quinine (100 M) but not TEA (5–50 mM) markedly reduced its amplitude. However, at similar concentrations as required to inhibit the hump, both apamin and quinine appeared to be poorly specific for Ca2+ -activated K+ currents in heart cells since they also inhibited the L-Type Ca2+ current. It is concluded that a long lasting Ca2+ -activated outward current, probably mainly carried by K+ ions but not sensitive to TEA, exists in atrial myocytes which is responsible for the current hump of the background I-V curve. 相似文献
62.
BACKGROUND: The identification of 'unknown' allergic sensitizations may determine the prognosis and treatment of patients with respiratory airway disease. Currently, the presence in homes of 'exotic' animals as pets is increasing. In this article the Siberian hamster or dwarf hamster (Phodopus sungorus) was identified as a new indoor source of aeroallergens and respiratory disease. METHODS: The subjects were six outpatients who were treated for asthma and rhinitis. Siberian hamster hair extract was prepared with a standard wt/vol method, and patients were skin-prick tested with the extract. Serum-specific immunoglobulin (Ig)E against the Siberian hamster, common hamster (Cricetus cricetus) and golden hamster (Mesocricetus auratus) was determined. IgE-immunoblotting was also performed for all six sera. Specific bronchial challenge was carried out with the Siberian hamster extract. RESULTS: Skin prick tests (SPT) with the Siberian hamster extract, and specific IgE-antibodies against Siberian hamster, were strongly positive in all six patients. Determinations of specific IgE-antibodies against C. cricetus and M. auratus were negative in all patients. IgE-immunoblotting of the sera revealed two IgE-binding fractions (MW 18 and 32 kDa) in five of the six sera. Specific bronchial provocation tests resulted in early asthmatic responses in the two patients who were challenged. CONCLUSIONS: The present study reveals the Siberian hamster to be able to induce both sensitization and disease, and this species of hamster should be taken into consideration as a cause of respiratory disease in exposed subjects. A noteworthy finding was the lack of sensitization in our patients to common hamster allergens (M. auratus and C. cricetus) that are usually tested when hamster allergy is suspected. 相似文献
63.
Vieta E Gastó C Colom F Reinares M Martínez-Arán A Benabarre A Akiskal HS 《Journal of affective disorders》2001,67(1-3):213-219
BACKGROUND: Since treatment approaches thought to be useful for mania are presumably suitable for hypomania as well, little systematic research has been done on the treatment of hypomanic episodes and their long-term outcome. As systematic trials have shown that the atypical antipsychotic risperidone may be effective and safe in the treatment of acute mania, we decided to conduct an open-label study of its effectiveness and tolerability in hypomania associated with bipolar II. METHODS: Forty-four DSM-IV bipolar II patients with Young Mania Rating Scale (YMRS) scores above 7 were included and followed-up for 6 months. Efficacy was measured by means of the YMRS and the Clinical Global Impression for Bipolar Disorder (CGI-BD). Treatment-emergent depression was measured by the Hamilton Depression Rating Scale (HDRS-17), and the Udvalg for Kliniske Unders?gelser (UKU) subscale was used for neurological/extrapyramidal side-effects. RESULTS: Thirty-four patients completed the trial. The mean dose of risperidone at endpoint was 2.8 mg/day. Last observation-carried-forward analysis showed significant reduction of YMRS scores from the first week of treatment, which continued until the endpoint (P<0.0001). At 6-month follow-up, 60% of patients were assymptomatic according to the CGI. The 32% who received risperidone in monotherapy seemed to respond equally well. Risperidone, as used in this study, appeared to be most protective against hypomanic than depressive recurrences. Nine patients (12%) had a depressive relapse during 6-month follow-up, one patient (2%) had an hypomanic relapse and another (2%) had both. No patients developed tardive dyskinesia during the duration of the study. Although most patients received risperidone in combination with standard mood-stabilizers, only three patients discontinued risperidone because of other side-effects. LIMITATIONS: In the absence of a placebo arm, it is uncertain to what extent the foregoing results could be ascribed to spontaneous remission of bipolar II disorder. CONCLUSIONS: Risperidone, either in combination with mood-stabilizers or alone was well-tolerated in bipolar II patients, who presented in a hypomanic state, and appeared efficacious. Further controlled research on the role of atypical antipsychotics in the treatment of less-than-manic forms of bipolar illness is warranted. 相似文献
64.
65.
Time course of hypo-osmotic swellings of human spermatozoa: evidence of ordered transition between swelling subtypes 总被引:2,自引:1,他引:2
Hossain AM; Rizk B; Barik S; Huff C; Thorneycroft IH 《Human reproduction (Oxford, England)》1998,13(6):1578-1583
The hypo-osmotic swelling test (HOST or HOS test) usually takes into
consideration the total HOS response value with no emphasis either on the
value of the response subtypes or the response evaluation time. This study
investigated the time course of HOS responses and analysed their
physiological relevance. Raw semen spermatozoa and Percoll washed
spermatozoa were used in the experiment. The morphological changes in the
sperm tail were monitored by incubating the spermatozoa in the hypo-
osmotic solution for 16 different time periods. The HOS reactive
spermatozoa and the type of HOS reaction (swelling subtypes) of the samples
subjected to different duration of treatment were identified under a phase
contrast microscope. Also the fate of individual spermatozoa in a
hypo-osmotic environment were monitored for 30 min. In spermatozoa exposed
to a hypo-osmotic solution, the motility lasted usually less than 2 min and
motility characteristics were uniquely different from that of the
spermatozoa under iso-osmotic conditions. The HOS response development was
permanent but the motility loss due to hypo-osmotic shock was reversible up
to 1 min of incubation. There was an indication of ordered transition among
the HOS swelling subtypes apparently initiating with subtype b destined to
c, d, e, f and g. Further, the subtypes a and g showed gradual decrease and
increase, respectively, while subtype b showed abrupt initial increase and
then gradual decrease. Transition from b to g could be direct or via one or
more than one subtypes. Ultrastructure based analysis indicated that HOS
response subtypes are the apparent reflection of the differences in the
cytoskeletal assembly of the sperm tail and thus may be identifying
different physiological variants in the sperm population. These results
indicate that shorter incubation is essential to document the kinetics of
various HOS responses but the conventional HOS test misses these important
HOS features because of lengthy incubation. Since the time course of
ordered transition of HOS responses will vary more than the total HOS
response in semen of different aetiologies, the importance of HOS response
subtypes and response evaluation time should be taken into consideration
when applying HOS test.
相似文献
66.
Pardo J Peled Y Bar J Hod M Sela BA Rafael ZB Orvieto R 《Human reproduction (Oxford, England)》2000,15(1):224-226
Low serum vitamin B(12) concentrations in pregnancy may not indicate true megaloblastic anaemia. In the present study we compared biochemical indices of vitamin B(12) deficiency (serum homocysteine and urine methylmalonic acid) in non-anaemic pregnant women with and without low serum vitamin B(12) concentrations. The groups were matched for age, parity and gestational age. No differences were found, and all values were within normal range. These results suggest that the measurement of low serum B(12) concentrations in pregnant women should be followed by analysis at the biochemical level before vitamin B(12) injections are started. 相似文献
67.
One of the first useful products from the human genome will be a set of predicted genes. Besides its intrinsic scientific interest, the accuracy and completeness of this data set is of considerable importance for human health and medicine. Though progress has been made on computational gene identification in terms of both methods and accuracy evaluation measures, most of the sequence sets in which the programs are tested are short genomic sequences, and there is concern that these accuracy measures may not extrapolate well to larger, more challenging data sets. Given the absence of experimentally verified large genomic data sets, we constructed a semiartificial test set comprising a number of short single-gene genomic sequences with randomly generated intergenic regions. This test set, which should still present an easier problem than real human genomic sequence, mimics the approximately 200kb long BACs being sequenced. In our experiments with these longer genomic sequences, the accuracy of GENSCAN, one of the most accurate ab initio gene prediction programs, dropped significantly, although its sensitivity remained high. Conversely, the accuracy of similarity-based programs, such as GENEWISE, PROCRUSTES, and BLASTX was not affected significantly by the presence of random intergenic sequence, but depended on the strength of the similarity to the protein homolog. As expected, the accuracy dropped if the models were built using more distant homologs, and we were able to quantitatively estimate this decline. However, the specificities of these techniques are still rather good even when the similarity is weak, which is a desirable characteristic for driving expensive follow-up experiments. Our experiments suggest that though gene prediction will improve with every new protein that is discovered and through improvements in the current set of tools, we still have a long way to go before we can decipher the precise exonic structure of every gene in the human genome using purely computational methodology. 相似文献
68.
Sonic hedgehog guides commissural axons along the longitudinal axis of the spinal cord 总被引:2,自引:0,他引:2
Bourikas D Pekarik V Baeriswyl T Grunditz A Sadhu R Nardó M Stoeckli ET 《Nature neuroscience》2005,8(3):297-304
Dorsal commissural axons in the developing spinal cord cross the floor plate, then turn rostrally and grow along the longitudinal axis, close to the floor plate. We used a subtractive hybridization approach to identify guidance cues responsible for the rostral turn in chicken embryos. One of the candidates was the morphogen Sonic hedgehog (Shh). Silencing of the gene SHH (which encodes Shh) by in ovo RNAi during commissural axon navigation demonstrated a repulsive role in post-commissural axon guidance. This effect of Shh was not mediated by Patched (Ptc) and Smoothened (Smo), the receptors that mediate effects of Shh in morphogenesis and commissural axon growth toward the floor plate. Rather, functional in vivo studies showed that the repulsive effect of Shh on postcommissural axons was mediated by Hedgehog interacting protein (Hip). 相似文献
69.
70.
A human homologue of Drosophila minibrain (MNB) is expressed in the neuronal regions affected in Down syndrome and maps to the critical region 总被引:4,自引:0,他引:4