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Koichi Masuda Robert L Sah Michael J Hejna Eugene J-M A Thonar 《Journal of orthopaedic research》2003,21(1):139-148
Most attempts to tissue-engineer cartilage have involved seeding of cultured cells into a biological or synthetic scaffold. We have developed a novel two-step culture approach that makes possible the in vitro formation of cartilaginous-like tissue by mature adult bovine chondrocytes without the aid of a synthetic matrix. The first step consists of culturing chondrocytes under conditions that maintain their rounded shape and their molecular phenotype as assessed by type II collagen and aggrecan production. This step was accomplished by culturing the isolated chondrocytes in alginate beads until the cells have reestablished a proteoglycan-rich cell-associated matrix (CM). The second step consists of culturing the cells with their CM, after recovery from the beads, on a tissue culture insert with a porous membrane. In this study, young adult bovine articular chondrocytes were cultured in alginate beads in the presence of 10% or 20% fetal bovine serum (FBS). After 7 days of culture, the alginate beads were dissolved by incubating the beads for 20 min in sodium citrate buffer, a calcium chelator. Following a brief centrifugation, the cells with their CM were recovered, resuspended in medium containing 10% or 20% FBS and seeded onto a tissue culture insert. After 1 week of culture on the insert, the individual cells with their CM progressively became incorporated into a mass of cartilaginous tissue. Culture with 20% FBS resulted in the best formation of tissues. These tissues, easily recovered from the insert, were then subjected to biochemical and histological analyses. The biochemical results showed that the chondrocytes remain phenotypically stable in the tissues. The de novo tissue has a relatively high ratio of PG/collagen. Histological examination of the tissue revealed it contained a cartilage-like matrix strongly stained with toluidine blue. This scaffold-free system appears ideal to study, in vitro, the development of transplantable cartilaginous tissue. 相似文献
23.
Jay Magaziner Eleanor M. Simonsick T. Michael Kashner J. Richard Hebel 《Journal of clinical epidemiology》1988,41(11)
The present study evaluates the response comparability between 361 elderly hip fracture patients admitted from the community to seven Baltimore area hospitals between 1984 and 1986 and interviewer selected proxies on items pertaining to patients' pre-fracture health and functional status. Agreement across items ranges from very poor to good and varies with respect to the health or functional area assessed. Proxies tend to overestimate patient disability relative to the patients themselves, especially with regard to capacity to perform instrumental activities of daily living. Although proxies who report the greatest contact with patients respond most comparably to the patients, when they do disagree, proxies with the greatest patient contact tend to overestimate patient disability. The authors suggest that attention to item construction and phrasing may improve response comparability. 相似文献
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Fos Expression in the Rat Brain Following Vaginal-Cervical Stimulation by Mating and Manual Probing 总被引:4,自引:2,他引:2
Marc J. Tetel Michael J. Getzinger Jeffrey D. Blaustein 《Journal of neuroendocrinology》1993,5(4):397-404
Vaginal-cervical stimulation (VCS), provided by mating or manual probing, induces many reproductive behavioral and endocrine changes in female rats. These changes include an increase in lordosis duration, heat termination and pseudopregnancy. Electro-physiological and [14C]2-deoxy-D-glucose studies collectively show that neurons in the medial preoptic area, ventromedial hypothalamus and midbrain central gray respond to manual VCS. In the present study we immunocytochemically labeled brain sections for Fos, the protein product of the immediate early gene c-fos, to detect VCS-responsive neurons in hormone-primed animals receiving VCS by mating or manual probing. In Experiment 1, females receiving mounts and intromissions were compared to: 1) vaginally-masked females receiving mounts but no VCS, 2) females exposed to an intact anesthetized male or 3) females not exposed to males or the testing arena. Those animals receiving VCS showed a dramatic increase in the number of Fos-immunoreactive cells in the medial preoptic area, posterodorsal portion of the medial amygdala and bed nucleus of the stria terminalis, as well as the dorsomedial hypothalamus, ventromedial hypothalamus and midbrain central gray. These effects of VCS were confirmed in Experiment 2 in animals receiving manual vaginal-cervical probing. These findings extend previous electrophysiological and [14C]2-deoxy-D-glucose studies by providing evidence that additional brain areas respond to VCS by mating, as well as manual probing. 相似文献
26.
Serotonin (5-HT) is a mediator (through 5-HT1P receptors) of slow EPSPs in myenteric ganglia of the small intestine. The effect of 5-HT can be mimicked by elevating cAMP; therefore, we tested the hypothesis that the slow EPSP-like response to 5-HT is cAMP-mediated. Guinea pig gut was enzymatically dissociated; myenteric ganglia remained intact and were collected by filtration. Neurons in the isolated ganglia retained their ability to manifest the slow EPSP-like response to 5-HT. Exposure to 5-HT raised the ganglionic level of cAMP (ED50 0.3 μM). This effect was not antagonized by the 5-HT1P antagonist, N-acetyl-5-hydroxytryptophyl-5-hydroxytryptophan amide (100.0 μM), or mimicked by the 5-HT1P agonist, 5-hydroxyindalpine (10.0 μM). Increases in cAMP were also evoked by the 5-HT1 agonist, 5-carboxyamidotryptamine (10.0 μM), the 5-HT2 agonist, (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI; 1.0–10.0 μM), and by the 5-HT4 agonists, renzapride (1.0–10.0 μM) and 5-methoxytryptamine (1.0–10.0 μM); however, neither the 5-HT1/5-HT2 antagonists, spiperone, methysergide, and methiothepin, nor the 5-HT4 antagonist, tropisetron (ICS 205–930; 10.0 μM), were able to inhibit the rise in cAMP evoked by these compounds or by 5-HT (0.1–10.0 μM). The 5-HT-evoked elevation of cAMP was antagonized by ketanserin (10.0 μM), which also blocked the effects of 5-methoxytryptamine and DOI, but not those of renzapride. The effective concentration of DOI, however, was higher than that needed for activation of 5-HT2 receptors, and Northern analysis using a cDNA probe encoding the rat 5-HT2 receptor failed to reveal the presence of 5-HT2 mRNA in myenteric ganglia, although it hybridizes with mRNA of the right size in the guinea pig brain. Compounds that failed to change levels of cAMP or to antagonize the action of 5-HT included 8-hydroxy-di-n-propylamino tetralin, R58639, R88226, and sumatriptan. It is concluded that the receptor responsible for the 5-HT-induced rise in cAMP in ganglia isolated from the guinea pig myenteric plexus is not a known subtype of 5-HT receptor. Since the pharmacology of this novel receptor is different from that of the slow EPSP-like response to 5-HT, the receptor probably does not mediate the slow EPSP. © 1993 Wiley-Liss, Inc. 相似文献
27.
Dr. Michael Gosland Pharm.D. Dr. Bert Lum Pharm.D. Dr. Julia Schimmelpfennig Pharm.D. Dr. James Baker Pharm.D. Dr Michael Doukas M.D. 《Pharmacotherapy》1996,16(1):16-39
Cisplatin in combination with other cytotoxic agents is the backbone for a potential cure of testicular germ cell neoplasms and is a critical factor in the substantial activity observed in the treatment of small cell lung cancer, bladder cancer, and ovarian germ cell tumors. Resistance to cisplatin at the onset of treatment or at relapse limits its curative potential, however. Laboratory studies using both cells selected for cisplatin resistance by exposure to sublethal concentrations and biopsy specimens from patients' tumors provide insights for the potential mechanisms of resistance. The mechanisms identified in vitro include a complex and wide array of related and unrelated pathways such as alterations in cellular drug transport, enhanced DNA repair dependent and independent of signal transduction pathways, and enhanced intracellular detoxification such as glutathione and metallothionein systems. Studies of these mechanisms have identified a number of agents with known potential for administration to humans and that reverse cisplatin resistance in vitro; for example, reversal of cellular accumulation defects by dipyridamole; inhibition of DNA repair by hydroxyurea, pentoxifylline, and novobiocin; inhibition of the glutathione system by ethacrynic acid and buthionine sulfoximine; and inhibition of signal transduction pathways by cyclosporine, tamoxifen, and calcium channel-blocking agents. Current phase I clinical trials are focusing on the most effective doses and schedules to administer these agents in combination with cisplatin. Initial uncontrolled trials in limited numbers of patients suggest that the addition of modulators of cisplatin has the potential to reverse resistance in patients previously failing therapy. Another promising avenue for circumventing cisplatin resistance is the development of noncross-resistant platinum analogs. 相似文献
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Steven Ganzberg Richard A Pape F Michael Beck 《Journal of oral and maxillofacial surgery》2002,60(3):244-50; discussion 250-1
PURPOSE: Remifentanil is a new, short-acting opioid that is similar pharmacodynamically to currently available opioids but differs in its pharmacokinetics. In the present study, we compared the use of remifentanil with the use of meperidine during intravenous conscious sedation for third molar surgery. PATIENTS AND METHODS: Forty patients who were scheduled for the removal of impacted third molars were randomly assigned to undergo 1 of 2 intravenous conscious sedation techniques. For both groups, 50:50 nitrous oxide oxygen were administered via nasal hood, and midazolam was titrated to Verril's sign. Twenty patients each then received either remifentanil 0.05 microgram/kg/min or meperidine 50 mg. Both patients and surgeons were blinded to the narcotic that was used. Blood pressure, heart rate, and oxygen saturation were determined before sedation and every 5 minutes during surgery. Recovery was measured using serial Trieger tests every 5 minutes after surgery. Patient and surgeon satisfaction of the quality of sedation was measured with a visual analog scale. RESULTS: Peak heart rate (91 beats/min for remifentanil vs 107 beats/min for meperidine, P <.01) and peak systolic blood pressure (131 mm Hg for remifentanil vs. 142 mm Hg for meperidine, P <.05) were significantly lower for the remifentanil group. Although there was a trend toward increased surgeon satisfaction with remifentanil (86 of 100 with remifentanil vs. 73 of 100 with meperidine), it was not found to be statistically significant. Likewise, other physiologic parameters were not found to be statistically significant. CONCLUSIONS: The lower peak heart rate and systolic blood pressure levels indicate that remifentanil may allow for less fluctuation in cardiovascular parameters. This could prove beneficial in patients with cardiovascular compromise. 相似文献
30.
Michael Innes 《The British journal of general practice》2002,52(479):502-502