Abnormal electrical properties of myocytes from chronically infarcted canine heart. Alterations in Vmax and the transient outward current.

BACKGROUND. Reentrant ventricular arrhythmias can occur in the surviving muscle fibers of the epicardial border zone of the canine heart 5 days after coronary artery occlusion. To understand the cellular basis of these arrhythmias, we developed a method of dispersing myocytes (IZs) from the epicardial border zone. METHODS AND RESULTS. We compared the electrophysiological properties of IZs with those of cells dispersed from the epicardium of control noninfarcted (NZs) and of sham-operated animals (NZsham). Transmembrane action potentials of IZs are reduced in total action potential amplitude and maximum upstroke velocity compared with NZs. However, resting potential of IZs is no different from that of NZs. Action potential duration at -10 mV is significantly reduced in IZs compared with control, and IZ potentials do not show the typical "spike and dome" morphology that is evident in all NZs. Using Vmax as an indirect measure of the peak inward current available for the upstroke of the action potential, we found that the availability curve for IZs is significantly different from the NZ curve. Furthermore, the time course of recovery of Vmax after a depolarizing voltage clamp step was significantly altered in IZs. Using whole-cell voltage clamp techniques, we determined that the voltage-dependent, Ca(2+)-independent, 4-aminopyridine-sensitive transient outward current (ito1) occurred in all NZs (n = 16) but existed in only 37% of IZs (n = 16). There was a significant reduction in the density of ito1 elicited by depolarizing steps in those IZs showing ito1 compared with ito1 density in NZs. CONCLUSIONS. We have developed a single-cell model of cells that survive in the infarcted heart. Our studies indicate that there are changes in Vmax in IZs. In addition, there is no prominent phase 1 of repolarization in IZ action potentials. This is consistent with the dramatic loss in the function of the ionic channel responsible for the voltage-dependent transient outward current, ito1.     

Novel Method for Processing Respiratory Specimens for Detection of Mycobacteria by Using C18-Carboxypropylbetaine: Blinded Study

A novel method for processing respiratory specimens to improve culture and acid-fast staining of mycobacteria is introduced. This new method utilized N,N-dimethyl-N-(n-octadecyl)-N-(3-carboxypropyl)ammonium inner salt (Chemical Abstract Service no. 78195-27-4), also known as C₁₈-carboxypropylbetaine (CB-18). In a blinded, five-center study, CB-18-based processing was compared to the standard method combining NALC and NaOH (NALC/NaOH). A total of 573 respiratory specimens were tested. Individual specimens were split approximately equally; the host institutions processed half of each specimen by the NALC/NaOH method, while the other half was processed with CB-18 at Quest Diagnostics—Baltimore. A total of 106 specimens were culture positive for acid-fast bacilli (AFB). Replacement of the primary decontamination agent with CB-18 caused changes in all diagnostic parameters. Aggregate culture sensitivity improved by approximately 43% (P < 0.01), and smear sensitivity improved by approximately 58% (P < 0.01). The sensitivity of smear relative to that of M. tuberculosis isolates exceeded 93% (P < 0.01) when specimens were processed with CB-18. The average times to a positive result were reduced by 7.3 days in liquid culture (P < 0.01) and 5.3 days on solid media (P < 0.05); however, the CB-18 method had a 20.8% contamination rate in liquid culture versus a rate of approximately 7.5% with NALC/NaOH processing. There were also unusual reductions in liquid culture sensitivity and smear specificity among CB-18-processed specimens. The characteristics of the latter parameters suggested that refinement of the CB-18 processing method should allow further improvements in culture sensitivity. This study showed that the CB-18 method has the potential to improve both smear and culture detection for these important human pathogens.     

Sleep and posttraumatic rheumatic pain modulation disorder (fibrositis syndrome)

The clinical features and sleep physiology of 11 female patients with "fibrositis syndrome" or rheumatic pain modulation disorder (RPMD) were compared with 11 female postaccident pain (PAP) patients who complained of widespread musculoskeletal pain, fatigue, and nonrestorative sleep following a nonphysically injurious motor vehicle or work-related accident. Both groups had similar musculoskeletal pain, fatigue, sleepiness and an alpha (7.5-11 Hz) EEG non-rapid eye movement (NREM) sleep anomaly. A psychophysiologic arousal mechanism during NREM sleep induced by the emotional stress of the accident may mediate the subsequent nonrestorative sleep, musculoskeletal pain, and fatigue symptoms in the posttraumatic pain disorder.     

GABAergic boutons establish synaptic contacts with the soma and dendrites of cuneothalamic relay neurons in the rat cuneate nucleus

This study investigates the synaptic relation between -aminobutyric acid-immunoreactive (GABA-IR) and cuneothalamic relay neurons (CTNs) in the rat cuneate nucleus. Retrograde transport of wheat germ agglutinin conjugated with horseradish peroxidase complex (WGA-HRP) was used to label CTNs while anti-GABA immunogold serum was used for the detection of GABA-IR boutons associated with CTNs. With these procedures, immunogold-labelled GABA-IR boutons were found to form axosomatic, axodendritic and axospinous synapses with the WGA-HRP-labelled but immunonegative CTNs. Quantitative estimation showed that the mean ratios of GABA-IR to GABA-immunonegative boutons making synaptic contacts with somata, proximal dendrites, and distal dendrites were 47.9%, 49.1% and 34.7%, respectively. Statistical analysis showed that the incidence of GABA-IR boutons on the somata and proximal dendrites of CTNs was significantly higher than on the distal dendrites. Our results indicate that GABA is the primary inhibitory neurotransmitter in the cuneate nucleus, thereby emphasizing the importance of postsynaptic inhibition on cuneothalamic relay neurons.     

Microtubules are required for cytokeratin aggresome (Mallory body) formation in hepatocytes: an in vitro study

Mallory bodies are cytokeratin-ubiquitin aggresomes that form in hepatocytes in many different chronic liver diseases. One of the key components in aggresome formation, not yet investigated in Mallory body formation, is the role of microtubules. An in vitro tissue culture assay is required to test for microtubule involvement in Mallory body formation so that Mallory body formation can be observed in the presence or absence of microtubule-disrupting agents. In this report, a new model of in vitro Mallory body formation was developed, which uses cultured hepatocytes isolated from drug-primed mice. When hepatocytes were incubated in the presence of antimicrotubule agents, they failed to form Mallory bodies. It is concluded that intact microtubules are required for Mallory body formation.     

上矢状窦三维断层解剖及其临床意义

目的：为给临床影像诊断提供解剖依据，方法：应用２４例头部标本研究了上矢状窦的三维断层解剖，结果：在正中矢状断层内，上矢状窦呈前窄后宽的弯曲裂隙，在冠状和横断层中，上矢状窦呈圆形，椭圆形，三角形和楔形，并测量了有关数据，结论：上矢状窦在各断层内的形态与其和人体横断面及冠状面所成的角度有关。     

CD40 signaling regulates innate and adaptive activation of microglia in response to amyloid beta-peptide

Although deposition of amyloid beta-peptide (Abeta) as Abeta plaques involves activation of microglia-mediated inflammatory responses, activated microglia ultimately fail to clear Abeta plaques in the brains of either Alzheimer's disease (AD) patients or AD mouse models. Mounting evidence suggests that chronic microglia-mediated immune response during Abeta deposition etiologically contributes to AD pathogenesis by promoting Abeta plaque formation. However, the mechanisms that govern microglia response in the context of cerebral Abeta/beta-amyloid pathology are not well understood. We show that ligation of CD40 by CD40L modulates Abeta-induced innate immune responses in microglia, including decreased microglia phagocytosis of exogenous Abeta(1-42) and increased production of pro-inflammatory cytokines. CD40 ligation in the presence of Abeta(1-42) leads to adaptive activation of microglia, as evidenced by increased co-localization of MHC class II with Abeta. To assess their antigen-presenting cell (APC) function, cultured microglia were pulsed with Abeta(1-42) in the presence of CD40L and co-cultured with CD4(+) T cells. Under these conditions, microglia stimulate T cell-derived IFN-gamma and IL-2 production, suggesting that CD40 signaling promotes the APC phenotype. These data provide a mechanistic explanation for our previous work showing decreased microgliosis associated with diminished cerebral Abeta/beta-amyloid pathology when blocking CD40 signaling in transgenic Alzheimer's mice.     

侧脑室计算机三维重建及理论分析

目的 :建立便于推广、功能齐全、价廉的三维医学图像重建系统及进行三维重建。方法 :利用目前较先进的数码摄片技术和自行编制的软件系统 ,对层距 1.0 mm的人体头部断面共 2 4 0层进行侧脑室的三维重建 ,同时对头部整体行三维重建以其进行相对定位和比较。结果 :重建后的侧脑室可和头部进行参照显示 ,行旋转、透明处理和不同方向的任意剖割。结论 :较以 CT、MRI断面图像重建的模型增加了轮廓的准确性和器官内组织的鲜明色彩     

Diurnal sleep/wake-related immune functions during the menstrual cycle of healthy young women

SUMMARY  Animal and human studies have related the sleeping/waking brain to the immune system. Because women are more susceptible to certain immunological illnesses, and sex steroids regulate immune functions, it was investigated whether the diurnal sleep/wake pattern of aspects of cellular immune functions and interleukin-1 (IL-1) and IL-2-like activities differed during low and high progesterone phases of the menstrual cycle.
Eleven healthy women, mean age 24y, were assessed over 24h with serial venous blood samples. Peripheral blood monocytes were assayed for mitogen responses, i.e. phytohemagglutin (PHA) and pokeweed (PWM) and natural killer (NK) cell activities. Plasma was assayed for IL-1 and IL-2-like activities, cortisol and progesterone. Data were standardized by Z transformation and analysed by repeated-measures analysis of variance by comparing high ( N = 5) vs. low ( N = 6) progesterone phases.
During the high progesterone phase, delayed slow-wave sleep (SWS) onset time and reduced amount of SWS was accompanied by a delay in the decline of NK cell activity, but rise in PHA activity following sleep onset. With the low progesterone phase, the pattern was similar to men with an early sleep decline in NK cell and late sleep rise in PHA activities. PWM rose during the night and plasma IL-1-like activity peaked during midday and during nocturnal sleep irrespective of the amount of progesterone.
Slow-wave sleep and sleep-related NK cell and PHA activities differed over the menstrual cycle, but not PWM response. Increases in plasma IL-1 functions during midday and night are consistent with predisposition to sleepiness during these times.     

Lengthening shortened penis caused by Peyronie's disease using circular venous grafting and daily stretching with a vacuum erection device

PURPOSE: We evaluated the results of chronic intermittent stretching with a vacuum erection device after circumferential tunical incision and circular venous grafting in 4 patients with penile shortening from severe Peyronie's disease. MATERIALS AND METHODS: We performed complete circumferential tunical incision and covered the defect with a circular venous graft in 4 patients with shortened penis as a result of Peyronie's disease. Preoperative evaluation included determination of patient and partner expectations, potency status, measurement of penile length after intracavernous injection and color duplex ultrasonography to determine possible vascular communication. Lower saphenous, upper saphenous and deep dorsal veins served as graft materials. We advised patients to use a vacuum device on a daily basis for 6 months starting 1 month after surgery. Postoperative evaluations were done at 6 and 18 months postoperatively. RESULTS: At 6-month followup 1 patient who did not use the vacuum device gained 1 inch in penile length and was not available for further followup. The other 3 patients each gained 2 inches but had decreased erectile rigidity due to narrowing in the grafted area (hourglass deformity). One patient who wanted a more natural erection elected penile prosthesis implantation about 1 year after grafting. The remaining 2 patients gained 3 inches at 18-month followup and regained partial penile rigidity similar to preoperative erections when the hourglass deformity improved. All patients were satisfied and indicated that surgery improved psychological well-being as well as relationships with partners. CONCLUSIONS: The results in this small group are satisfactory. Our technique offers a reasonable solution for correction of penile shortening in patients with Peyronie's disease.