Inconsistent effects of all-trans retinoic acid on different clones of chemically transformed rat liver epithelial cells

The effects of all-trans retinoic acid (RA) on the growth andbiochemical properties of five clonal strains of neoplasticallytransformed rat liver epithelial cells were studied. These cellstrains were derived clonally from a single line of normal diploidrat liver epithelial cells that had been transformed by treatmentwith N-methyl-N'-nitro-N-nitrosoguanidine. The results showthat RA induces inconsistent alterations in selected phenotypicproperties of these five different cell strains. Retinoic acideither depressed, enhanced or produced no effect on the colony-formingability in soft agar, on the activity of -glutamyl transpeptidase,on the amount of cell-associated fibronectin, and on the bindingcapacity of ¹²⁵I-epidermal growth factor (EGF). The only consistentcorrelation observed among cell strains was between the cellularability to grow in soft agar and the amount of cell-associatedfibronectin. Enhancement of anchorage-independent growth byretinoic acid was not mediated through changes in the numberof EGF receptors. Our data demonstrate that the responses toretinoic acid of clonal subpopulations of chemically transformedrat liver epithelial cells are inconsistent, even when the clonalsubpopulations are derived from a common precursor.     

Induction of spheroid cytoplasmic bodies in a rat muscle by local tetanus

The term "cytoplasmic body" or "spheroid body" myopathy refers to a heterogeneous group of familial or sporadic diseases characterized primarily by the presence of abundant spheroid or cytoplasmic bodies in the muscles. The morphogenesis of these inclusions remains unclear. This article describes the induction and evolution of spheroid cytoplasmic bodies (SCBs) in the rat plantaris muscle (PL) with local tetanus, which was induced in rats by the injection of a minute amount of tetanus toxin. In contrast to the tetanized soleus muscle (SOL), which developed core fibers (central cores, minicore, target fiber, targetoid fiber, and rods), the tetanized PL produced numerous SCBs with a predictable time course. They were induced in both type 1 and 2 fibers of PL, which is composed predominantly (95%) of type 2 fibers, in contrast to SOL (85% type 1 fibers). Factors inducing SCBs may include immobilization, shortening, intact innervation, and disuse atrophy.     

Effects of low-level microwave irradiation on amphetamine hyperthermia are blockable by naloxone and classically conditionable

In a series of experiments, we investigated the effects of pulsed low-level microwave irradiation on amphetamine-induced hyperthermia in the rat. Rats were irradiated in a 2,450-MHz cylindrical waveguide exposure system at 1 mW/cm², 2 s pulses, 500 pps, average SAR of 0.6 W/kg. Acute (45 min) exposure to microwaves attenuated amphetamine-induced hyperthermia. This effect was blocked by pretreatment of the animals with the narcotic antagonist naloxone. In another experiment, rats were subjected to ten daily sessions of microwave exposure (45 min/session). On day 11, amphetamine-induced hyperthermia was studied in the animals immediately after a session of either microwave or sham exposure. Similar to the acute effect, amphetamine-induced hyperthermia was attenuated in rats irradiated with microwaves (unconditioned effect). In the sham-irradiated animals we observed a potentiation of the amphetamine-induced hyperthermia, which was a conditioned effect of microwaves. Thus, the conditioned effect (potentiation) was opposite in direction to the unconditioned effect (attenuation). No tolerance developed to the unconditioned effect after subchronic exposure. Furthermore, both conditioned and unconditioned effects of microwaves on amphetamine-induced hyperthermia could be blocked by treatment with naloxone. These data suggest that (1) microwave irradiation may activate endogenous opioids, which in turn alter the actions of psychoactive drugs, and (2) the effect of microwaves on drug action can be classically conditioned. Offprint requests to: H. Lai     

新型冠状病毒肺炎患者死亡风险列线图模型的构建与验证

目的构建列线图模型以预测新型冠状病毒病2019(COVID-19)的死亡风险,以早期筛选死亡高危患者。 方法收集2020年1月至2020年4月武汉大学人民医院(东院)和2022年4月至2022年5月上海市第九人民医院(北院)收治COVID-19患者的临床资料。以武汉大学人民医院患者(166例)作为训练集,上海市第九人民医院患者(52例)作为验证集。采用先单因素后多因素Logistic回归分析确定死亡的独立危险因素,应用R语言构建列线图模型。采用受试者工作特征曲线(ROC)、C指数及校准曲线评估列线图模型的预测准确性及判断能力,决策曲线分析评估模型的临床应用价值。通过验证集对模型进行外部验证。 结果本研究共纳入重型/危重型COVID-19患者218例,其中67例(30.73%)死亡,多因素Logistic回归分析显示,≥3种基础疾病、APACHE Ⅱ评分(5~40分)、中性粒细胞/淋巴细胞(0~90)、乳酸(0~16mmol/L)均是死亡的独立危险因素。ROC曲线分析显示,训练集的曲线下面积(AUC)为0.869(95%CI：0.811~0.927),验证集AUC为0.797(95%CI：0.671~0.924),训练集与验证集校准曲线经Hosmer-Lemeshow拟合优度检验(P＝0.473,P＝0.421)。临床决策曲线分析表明,该列线图预测模型的临床应用价值高。 结论本研究构建COVID-19患者死亡风险列线图模型预测效能良好,可个体化、可视化、图形化预测,有助于医师早期做出合适临床决策及诊疗。     

Hypertrophic mononeuritis clinically presenting with painful legs and moving toes

A 40-year-old woman presented with progressive lower leg pain and spontaneous toe movement. The EMG showed a posterior tibial nerve mononeuropathy and continuous myokymic discharges in posterior tibial-innervated muscles. The MRI revealed a markedly enlarged posterior tibial nerve. Toe movements and myokymia were unaffected by the proximal transection of the lesion but ceased abruptly when the distal end of the fusiform "tumor" was resected, suggesting that spontaneous electrical foci may have been located along the nerve lesion. The markedly enlarged nerve segment contained edematous, swollen fascicles with marked Schwann cell onion-bulb lesions and angiocentric, lymphocytic, and lymphofollicular infiltration. This nerve lesion is an example of a newly recognized entity called hypertrophic mononeuritis.     

Synthesis and anti-HIV-1 activity of 2'-"up"-fluoro analogues of active anti-AIDS nucleosides 3'-azido-3'-deoxythymidine (AZT) and 2',3'-dideoxycytidine (DDC).

1-(3-Azido-2,3-dideoxy-2-fluoro-beta-D-arabinofuranosyl)thymine (6, F-AZT) and 1-(2,3-dideoxy-2-fluoro-beta-D-threopentofuranosyl)cytosine (12, F-DDC) were synthesized from the potent antiherpes virus nucleosides 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)thymine (1, FMAU) and 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-5-iodocytosine (FIAC) in the hope that introduction of a 2-"up"-fluoro substituent might potentiate the anti-HIV activity of AZT and DDC. FMAU (1) was converted in three steps into 2,3'-anhydro-1-(2-fluoro-2-deoxy-5-O-trityl-beta-D-lyxofuranosyl)thymine (4), which when treated with NaN3 followed by detritylation afforded 6. F-DDC was prepared by two methods. Tritylation of FIAC followed by treatment of the product with thiocarbonyldimidazole afforded the 5'-O-trityl-3'-O-(imidazolyl)thiocarbonyl nucleoside 9. Upon radical reduction of 9 with Bu3SnH and AIBN, 5'-O-trityl-DDC 10 was obtained. Compound 10 was detritylated to give 12, which (when obtained by this procedure) resisted crystallization, but the diacetate 12' was obtained in crystalline form. Alternatively, FAC (14) was converted into N4,O5'-dibenzoyl derivative 15, which was treated with thiocarbonyldiimidazole. Reduction of 16 with Bu3SnH/AIBN followed by debenzoylation afforded 12, which was obtained in crystalline form. F-AZT did not exhibit any significant activity against the human immunodeficiency virus (HIV) in vitro. F-DDC, however, showed activity against HIV-1, but the therapeutic index is much inferior to that of AZT.     

Detection of methyl ethyl ketone in urine using headspace solid phase microextraction and gas chromatography

Headspace solid-phase microextraction coupled with gas chromatography/flame ionization detection was developed to measure urinary methyl ethyl ketone (MEK). A fused silica fiber coated with 75 microns carboxen/polydimethylsiloxane was used to extract urinary MEK. The optimal extraction conditions were obtained when temperature was 50 degrees C, extraction time was 15 minutes, and ammonium sulfate concentration was 0.5 g/mL. The optimal desorption temperature and time were 200 degrees C and 5 minutes, respectively. The concentration range of calibration curves was 27 to 8000 ng/mL of MEK. The within-day and between-day pooled coefficients of variation (9 concentrations, triplicate samples) were 5.4% and 8.8%, respectively. The limit of detection and limit of quantitation were 4.2 ng/mL and 21.6 ng/mL, respectively. The recovery (+/- standard deviation) of MEK was 100.2% +/- 8.6% (n = 3). MEK in urine was stable for at least 1 month when stored at -20 degrees C. This method proved to be applicable for the analysis of urinary MEK of exposed workers in a plastic material printing plant. We concluded that this new method is sensitive, inexpensive, simple, and reliable for measuring the occupational exposure of MEK.     

Cerebral uptake and metabolism of (11C) Vinpocetine in monkeys: PET studies]

Vinpocetine, a vinca alkaloid, is a therapeutic agent widely used in the treatment of acute and chronic stroke patients. To explore the uptake and distribution of vinpocetine in the primate brain, vinpocetine was labelled with 11C and positron emission tomography (PET) was used to measure the uptake and distribution of 11C-vinpocetine in the brain and the trunk of a cynomolgous monkey. HPLC was used to determine the concentration of vinpocetine and its labelled metabolites in blood and plasma. Following the radioligand's intravenous administration, after an initial peak, the total concentration of radioactivity in blood was relatively stable with time. The uptake of 11C-vinpocetine into the brain was rapid and about 5% of the total injected radioactivity was present in the brain two minutes after drug administration. These facts indicate that the compound passes the blood-brain barrier readily and enters the brain. The radioactivity uptake was heterogeneously distributed among brain regions. The highest concentrations were found in the thalamus, the basal ganglia and certain neocortical regions. In an earlier PET investigation on chronic stroke patients the highest increases in cerebral blood flow and glucose metabolism after intravenous vinpocetine treatment occurred in these anatomical structures. The heterogenous regional distribution of vinpocetine and the observation that the highest uptake values in brain structures go parallel with the greatest regional blood flow and glucose metabolic rate increases indicate that direct CNS effects of vinpocetine should be considered as an explanation for the therapeutic effects. The confirmation of this suggestion requires further investigations.     

Short-arm (1.9 m) +2.2 Gz acceleration: isotonic exercise load-O2 uptake relationship

BACKGROUND: The deconditioning syndrome from prolonged bed rest (BR) or spaceflight includes decreases in maximal oxygen uptake (VO2max), muscular strength and endurance, and orthostatic tolerance. In addition to exercise training as a countermeasure, +Gz (head-to-foot) acceleration training on 1.8-2.0 m centrifuges can ameliorate the orthostatic and acceleration intolerances induced by BR and immersion deconditioning. PURPOSE: Study A was designed to determine the magnitude and linearity of the heart rate (HR) response to human-powered centrifuge (HPC) acceleration with supine exercise vs. passive (no exercise) acceleration. Study B was designed to test the hypothesis that moderate +Gz acceleration during exercise will not affect the respective normal linear relationships between exercise load and VO2max, HR, and pulmonary ventilation (VEBTPS). Study C: To determine if these physiological responses from the HPC runs (exercise + on-platform acceleration) will be similar to those from the exercise + off-platform acceleration responses. METHODS: In Study A, four men and two women (31-62 yr) were tested supine during exercise + acceleration and only passive acceleration at 100% [maximal acceleration (rpm) = Amax] and at 25%, 50%, and 75% of Amax. In Studies B and C, seven men (33+/-SD 7 yr) exercised supine on the HPC that has two opposing on-platform exercise stations. A VO2max test and submaximal exercise runs occurred under three conditions: (EX) exercise (on-platform cycle at 42%, 61%, 89% and 100% VO2max) with no acceleration; (HPC) exercise + acceleration via the chain drive at 25%,50%, and 100% Gzmax (35%, 72% and 100% VO2max); and (EXA) exercise (on-platform cycle at 42%, 61%, 89%, and 100% VO2max) with acceleration performed via the off-platform cycle operator at +2.2+/-0.2 Gz [50% of max (rpm) G]. RESULTS: Study A: Mean (+/-SE) Amax was 43.7+/-1.3 rpm (mean = +3.9+/-0.2, range = 3.3 to 4.9 Gz). Amax run time for exercise +acceleration was 50-70 s, and 40-70 s for passive acceleration. Regression of X HR on Gz levels indicated explained variances (r2) of 0.88 (exercise) and 0.96 (passive). The mean exercise HR of 107+/-4 (25%), to 189+/-13 (100%) bpm were 43-50 bpm higher (p < 0.05) than comparable passive HR of 64+/-2 to 142+/-22 bpm, respectively. Study B: There were no significant differences in VO2, HR or VEBTPS at the submaximal or maximal levels between the EX and EXA runs. Mean (+/-SE) VO2max for EX was 2.86+/-0.12 L x min(-1)(35+/-2 ml x min(-1) x kg(-1)) and for EXA was 3.09+/-0.14 L x min(-1) (37+/-2 ml-min(-1) x kg(-1)). Study C: There were no significant differences in the essentially linear relationships between the HPC and EXA data for VO2 (p = 0.45), HR (p < 0.08), VEBTPS (p = 0.28), or the RE (p = 0.15) when the exercise load was % VO2max. CONCLUSION: Addition of + 2.2 Gz acceleration does not significantly influence levels of oxygen uptake, heart rate, or pulmonary ventilation during submaximal or maximal cycle ergometer leg exercise on a short-arm centrifuge.     

Reliability of the American Medical Association guides' model for measuring spinal range of motion. Its implication for whole-person impairment rating

STUDY DESIGN: Repeated measures design for intra- and interrater reliability. OBJECTIVES: To determine the intra- and interrater reliability of the lumbar spine range of motion measured with a dual inclinometer, and the thoracolumbar spine range of motion measured with a long-arm goniometer, as recommended in the American Medical Association Guides. SUMMARY OF BACKGROUND DATA: The American Medical Association Guides (2nd and 4th editions) recommend using measurements of thoracolumbar and lumbar range of movement, respectively, to estimate the percentage of permanent impairment in patients with chronic low back pain. However, the reliability of this method of estimating impairment has not been determined. METHODS: In all, 34 subjects participated in the study, 21 women with a mean age of 40.1 years (SD, +/- 11.1) and 13 men with a mean age of 47.7 years (SD, +/- 12.1). Measures of thoracolumbar flexion, extension, lateral flexion, and rotation were obtained with a long-arm goniometer. Lumbar flexion, extension, and lateral flexion were measured with a dual inclinometer. Measurements were taken by two examiners on one occasion and by one examiner on two occasions approximately 1 week apart. RESULTS: The results showed poor intra- and interrater reliability for all measurements taken with both instruments. Measurement error expressed in degrees showed that measurements taken by different raters exhibited systematic as well as random differences. As a result, subjects measured by two different examiners on the same day, with either instrument, could give impairment ratings ranging between 0% and 18% of the whole person (excluding rotation), in which percentage impairment is calculated using the average range of motion and the average systematic and random error in degrees for the group for each movement (flexion, extension, and lateral flexion). CONCLUSIONS: The poor reliability of the American Medical Association Guides' spinal range of motion model can result in marked variation in the percentage of whole-body impairment. These findings have implications for compensation bodies in Australia and other countries that use the American Medical Association Guides' procedure to estimate impairment in chronic low back pain patients.