Recovery of Functional Memory T Cells in Lung Transplant Recipients Following Induction Therapy with Alemtuzumab

Profound T-cell depletion with the monoclonal antibody alemtuzumab facilitates reduced maintenance immunosuppression in abdominal and lung transplantation. While the phenotype of the post-depletional T cells has been characterized, little is known about their function. In the present study, global and CMV-specific T-cell function was assessed longitudinally in 23 lung transplant (LTx) recipients using T-cell assays (ImmuKnow and T Cell Memory, Cylex, Columbia, MD) during the first year posttransplant after induction therapy. Recovery of mitogen responses were seen at 2 weeks posttransplantation (65%PHA; 58% Con A), despite the low number of circulating T cells (<2%). These responses declined at 4-5 months (24%PHA; 54% Con A) and were partially reconstituted by 9 months (46% PHA; 73% Con A). CMV-specific responses recovered in 80% of R+ patients as early as 2 weeks posttransplant (n = 5) and 72% of patients had a memory response by 3 months (n = 11). In contrast, only 2 of 5 patients who did not exhibit memory responses pre-transplant (R-) developed transient CMV-specific T-cell responses. Our results show that profound depletion of T cells induced by alemtuzumab spares the functional subset of CMV-specific memory T cells. Conversely, CMV R- patients predepletion may require a prolonged period of prophylaxis.     

Flunarizine induces a transient loss of tyrosine hydroxylase immunoreactivity in nigrostriatal neurons

Neurotoxic effects of flunarizine (Fz), a selective calcium channel blocker, on the nigrostriatal dopamine system was investigated. Systemic injections of Fz to mice resulted in a transient loss of tyrosine hydroxylase (TH) immunoreactive nigrostriatal neurons without cell loss. TH immunoreactivity in these neurons was greatly reduced as rapidly as one day after drug administration (regardless of dosage used) and thereafter recovered in both dose- and time-dependent manners. Such a novel neurotoxic action of Fz may constitute a morphological substrate for reversible drug-induced parkinsonian signs described in recent clinical case reports.     

新型白细胞滤器LD-1对体外循环中红细胞的保护作用

目的研究一种新型白细胞滤器LD-1在体外循环(CPB)中对红细胞的保护作用。方法将25～30kg蒙古犬12只按随机数字表法分为对照组和LD-1过滤组(LD组),每组6只。对照组不使用白细胞滤器;LD组将白细胞滤器LD-1安装于CPB的静脉回流端,在CPB开始2min后打开滤器,过滤5min。分别于CPB前、CPB10min、40min、75min、停CPB和CPB后2h取静脉血测定白细胞(WBC)数量、血浆丙二醛(MDA)、超氧化物歧化酶(SOD)和游离血红蛋白(FHB)水平,并测定红细胞脆性。结果在CPB中各时间点LD组WBC数量均显著低于CPB前(P<0.01),且明显低于对照组(P<0.05);对照组血浆SOD水平在CPB75min后显著降低,而LD组血浆SOD水平在CPB75min、停CPB及CPB后2h均显著高于对照组(P<0.05,0.01);在CPB后各时间点LD组MDA水平均低于对照组,但无统计学意义;对照组在停CPB和CPB后2h,红细胞开始溶血和完全溶血所需的氯化钠浓度明显高于LD组(P<0.05);CPB后两组血浆FHB浓度均升高(P<0.01),但LD组在CPB40min后各时点均显著低于对照组(P<0.05)。结论新型白细胞滤器LD-1在CPB中能有效去除白细胞,保存血浆的抗氧化能力,抑制氧自由基对红细胞的破坏。     

Protective effectiveness of an endotoxin-depleted pertussis vaccine

Pertussis vaccine depleted of endotoxin by the polymyxin-Sepharose affinity chromatography method was tested for toxic activity and protective effectiveness in mice. Preparations containing 1000-fold and 1 000 O00-fold less endotoxin fulfilled the established experimental criteria for freedom from toxicity. A fourfold concentrate of the former demonstrated a protection rate only 10% less than that of standard, untreated pertussis vaccine.     

Changes in somatosensory evoked responses by repetition of the median nerve stimulation

OBJECTIVE: We investigate the synaptic factor for the recovery function of evoked responses using a repetitive stimulation technique. METHODS: Somatosensory evoked cortical magnetic field (SEF) was recorded following stimulation of the median nerve using single to 6-train stimulation in 8 healthy subjects. The SEF responses after each stimulus in the train stimulation were extracted by subtraction of the waveforms. RESULTS: An attenuation of the SEF components was recognized after the second of the stimuli, but there was no significant attenuation with the third or later stimulations. The root mean square (RMS) of the 1M (peak latency at 20 ms after stimulation) and 4M (70 ms) components were smaller than that of the single stimulation during the train stimulation, while the 2M (30 ms) and 3M (45 ms) components were not attenuated, but the 3M was facilitated at the fourth to sixth stimulation. CONCLUSION: The synaptic factor was not responsible for the attenuation of the SEF components during repetitive stimulation in healthy subjects. The SEF change disclosed a functional difference among the SEF components during the train stimulation, especially among the later components.     

Expression of Fos in rat brain in relation to sodium appetite: furosemide and cerebroventricular renin

Two experiments were performed to investigate the relationship between the expression of sodium appetite and the appearance of Fos-like immunoreactivity (Fos-IR) in the brain of rats. In the first experiment, rats were depleted of sodium by treatment with furosemide 24 h prior to sacrifice and without access to either food or sodium solution. Some rats had access to distilled water, and others had no fluids available during the 24 h. All of the furosemide-treated rats showed Fos-IR in both the subfornical organ (SFO) and around the organum vasculosum laminae terminalis (OVLT). Rats with access to distilled water during the depletion period showed no Fos-IR in the supraoptic (SON) or paraventricular hypothalamic nuclei (PVN) and, in parallel behavioral studies, comparably-treated rats consumed only 0.3 M NaCl solution at the end of the 24 h. In rats that had no fluids during the deprivation period, only about one half showed Fos-IR in SON and PVN and, in parallel behavioral studies, comparably treated rats consumed both water and 0.3 M NaCI solution at the end of 24 h. In a second experiment, cerebroventricular administration of renin stimulated short latency intake of 0.3 M NaCI and water. The relative intakes of water and NaCl were comparable at a low dose of renin, but intake of water exceeded that of NaCl after higher doses. Renin induced Fos-IR in SFO, MnPO, peri-OVLT region, SON and PVN. Both Fos-IR and fluid intake were antagonized by administration of losartan, an angiotensin 11 type 1 receptor antagonist. Thus, only the circumventricular organs of the lamina terminalis showed Fos-IR during each natriorexigenic regimen in these studies. These data support the view that Ang 11 of both central and peripheral origin activates the SFO and/or peri-OVLT region and contributes to sodium appetite.     

Mechanisms by which the putative serotonin receptor antagonist metitepin alters nociception in mice

Summary The putative serotonin (5-HT) receptor antagonist metitepin (0.5 mg/ kg, intraperitoneally) produced hypoalgesia in the increasing temperature hot-plate test and hyperalgesia in the tail-flick test in mice. The effects of metitepin were not altered after depletion of 5-HT by the neurotoxin 5,7-dihydroxytryptamine (5, 7-DHT, 80 g free base, intracerebroventricularly) or the serotonin synthesis inhibitor p-chlorophenylalanine (PCPA, 400 mg/kg for 10 consecutive days). After chronic administration (2 or 5 mg/kg for 18 consecutive days) tolerance to the effect of metitepin (0.5 mg/kg) and cross-tolerance to the antinociceptive effect of the 5-HT agonist 5-methoxy-N,N-dimethyltryptamine (5-MeODMT, 3 mg/kg) was found in the hot-plate test but not in the tail-flick test. It is suggested that metitepin may block descending 5-HT transmission while more complex mechanisms of action are involved at supraspinal level. One possibility is that metitepin exhibits partial agonist properties or, alternatively, that the drug may block 5-HT subsystems which tonically enhance nociception.     

Compartmentalization of single muscle units in cat lateral gastrocnemius

Summary The distribution of muscle fibers in single muscle units in cat lateral gastrocnemius (LG) muscle was analyzed using the method of glycogen depletion. Single, type FF motor units in LG were identified by stimulation of dissected ventral rootlets and then activated to produce depletion of glycogen in their innervated muscle fibers. Serial histological sections were made of the entire triceps surae muscles and then reacted for the demonstration of glycogen. Projected tracings of the sections were used to compare the distribution of glycogen depleted muscle fibers to the heads of the LG muscle. Results of analysis of single muscle units indicate that the muscle fibers innervated by single cat LG type FF motor units are distributed to the same regions of muscle which are innervated by primary branches of the nerve to the LG muscle. The single units are thus compartmentalized. These results support the hypothesis that each of the neuromuscular compartments of LG contains a unique population of motor units. It is suggested that compartmentalization of muscles about primary branches of their muscle nerves may from a major organizational principle in the design of skeletal muscles.     

The time course of glycogen depletion in single fibers of chronically stimulated rabbit fast-twitch muscle

A time course study was conducted to investigate the possibility of a relationship between fiber degeneration and glycogen depletion in chronically nerve-stimulated extensor digitorum longus muscle of the rabbit. Muscles were stimulated 12 h daily at 10 Hz using alternating one-hour periods of stimulation and rest. When measured for the first time after 3 h (1 h stimulation, 1 h rest, 1 h stimulation), microphotometry revealed complete glycogen depletion of all fiber types (fast glycolytic, FG; fast oxidative glycolytic, FOG; slow oxidative, SO). Different responses were noted beginning at day 4. At this time point, all FOG and SO fibers recovered their glycogen stores with some of the FOG population attaining levels higher than the FOG fibers in the unstimulated, contralateral muscle. Approximately 28% of the FG fibers recovered to normal glycogen values, whereas 58% remained depleted and 14% displayed overshoting glycogen levels. Fifteen percent of all fibers were glycogen-depleted after 12 days of stimulation. At this time, classic fiber types could no longer be distinguished. Fiber degeneration, which was recognized by the invasion of nonmuscle cells, began after 6 days and was restricted to the glycogen-depleted fibers. By this time, there was also a significant increase in DNA content. Exhaustions of glycogen, the main fuel of the FG fibers, is believed to cause a collapse of energy-supply and ATP-driven ionic pumps. The latter could be the initial step of fiber deterioration.